WO2020264132A1 - Wound inserts for treatment of tunneling wounds - Google Patents
Wound inserts for treatment of tunneling wounds Download PDFInfo
- Publication number
- WO2020264132A1 WO2020264132A1 PCT/US2020/039576 US2020039576W WO2020264132A1 WO 2020264132 A1 WO2020264132 A1 WO 2020264132A1 US 2020039576 W US2020039576 W US 2020039576W WO 2020264132 A1 WO2020264132 A1 WO 2020264132A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- wound
- wound insert
- outer layer
- insert
- inner core
- Prior art date
Links
- 208000027418 Wounds and injury Diseases 0.000 title claims abstract description 246
- 206010052428 Wound Diseases 0.000 title claims abstract description 245
- 230000005641 tunneling Effects 0.000 title claims abstract description 10
- 229920001222 biopolymer Polymers 0.000 claims abstract description 68
- 238000000034 method Methods 0.000 claims abstract description 63
- 238000004519 manufacturing process Methods 0.000 claims abstract description 8
- 108010035532 Collagen Proteins 0.000 claims description 54
- 102000008186 Collagen Human genes 0.000 claims description 54
- 229920001436 collagen Polymers 0.000 claims description 54
- 239000002002 slurry Substances 0.000 claims description 50
- 238000004132 cross linking Methods 0.000 claims description 19
- 229920001661 Chitosan Polymers 0.000 claims description 17
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 15
- 239000004014 plasticizer Substances 0.000 claims description 14
- -1 poly(glycolic acid) Polymers 0.000 claims description 14
- 239000004599 antimicrobial Substances 0.000 claims description 13
- 239000004332 silver Substances 0.000 claims description 13
- 229910052709 silver Inorganic materials 0.000 claims description 13
- 108010010803 Gelatin Proteins 0.000 claims description 12
- 229920000159 gelatin Polymers 0.000 claims description 12
- 239000008273 gelatin Substances 0.000 claims description 12
- 235000019322 gelatine Nutrition 0.000 claims description 12
- 235000011852 gelatine desserts Nutrition 0.000 claims description 12
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 claims description 9
- 229920002674 hyaluronan Polymers 0.000 claims description 9
- 229960003160 hyaluronic acid Drugs 0.000 claims description 9
- 230000001684 chronic effect Effects 0.000 claims description 8
- 150000004676 glycans Chemical class 0.000 claims description 8
- 229920001282 polysaccharide Polymers 0.000 claims description 8
- 239000005017 polysaccharide Substances 0.000 claims description 8
- 239000004627 regenerated cellulose Substances 0.000 claims description 8
- 229920002201 Oxidized cellulose Polymers 0.000 claims description 7
- 238000001035 drying Methods 0.000 claims description 7
- 229940107304 oxidized cellulose Drugs 0.000 claims description 7
- 238000000151 deposition Methods 0.000 claims description 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 4
- ZFOZVQLOBQUTQQ-UHFFFAOYSA-N Tributyl citrate Chemical compound CCCCOC(=O)CC(O)(C(=O)OCCCC)CC(=O)OCCCC ZFOZVQLOBQUTQQ-UHFFFAOYSA-N 0.000 claims description 4
- 230000001154 acute effect Effects 0.000 claims description 4
- HDDLVZWGOPWKFW-UHFFFAOYSA-N trimethyl 2-hydroxypropane-1,2,3-tricarboxylate Chemical compound COC(=O)CC(O)(C(=O)OC)CC(=O)OC HDDLVZWGOPWKFW-UHFFFAOYSA-N 0.000 claims description 4
- LDVVTQMJQSCDMK-UHFFFAOYSA-N 1,3-dihydroxypropan-2-yl formate Chemical compound OCC(CO)OC=O LDVVTQMJQSCDMK-UHFFFAOYSA-N 0.000 claims description 3
- XKGDWZQXVZSXAO-ADYSOMBNSA-N Ricinoleic Acid methyl ester Chemical compound CCCCCC[C@@H](O)C\C=C/CCCCCCCC(=O)OC XKGDWZQXVZSXAO-ADYSOMBNSA-N 0.000 claims description 3
- XKGDWZQXVZSXAO-SFHVURJKSA-N Ricinolsaeure-methylester Natural products CCCCCC[C@H](O)CC=CCCCCCCCC(=O)OC XKGDWZQXVZSXAO-SFHVURJKSA-N 0.000 claims description 3
- 206010012601 diabetes mellitus Diseases 0.000 claims description 3
- 230000002500 effect on skin Effects 0.000 claims description 3
- XKGDWZQXVZSXAO-UHFFFAOYSA-N ricinoleic acid methyl ester Natural products CCCCCCC(O)CC=CCCCCCCCC(=O)OC XKGDWZQXVZSXAO-UHFFFAOYSA-N 0.000 claims description 3
- BSXJTDJJVULBTQ-UHFFFAOYSA-N 2,2,3,3,4,4,5,5,6,6,7,7,8,8,9,9,9-heptadecafluorononan-1-ol Chemical compound OCC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F BSXJTDJJVULBTQ-UHFFFAOYSA-N 0.000 claims description 2
- QZCLKYGREBVARF-UHFFFAOYSA-N Acetyl tributyl citrate Chemical compound CCCCOC(=O)CC(C(=O)OCCCC)(OC(C)=O)CC(=O)OCCCC QZCLKYGREBVARF-UHFFFAOYSA-N 0.000 claims description 2
- 239000004804 Butyryltrihexylcitrate Substances 0.000 claims description 2
- 229920000954 Polyglycolide Polymers 0.000 claims description 2
- DOOTYTYQINUNNV-UHFFFAOYSA-N Triethyl citrate Chemical group CCOC(=O)CC(O)(C(=O)OCC)CC(=O)OCC DOOTYTYQINUNNV-UHFFFAOYSA-N 0.000 claims description 2
- 229910021529 ammonia Inorganic materials 0.000 claims description 2
- 238000004108 freeze drying Methods 0.000 claims description 2
- 229920002463 poly(p-dioxanone) polymer Polymers 0.000 claims description 2
- 239000000622 polydioxanone Substances 0.000 claims description 2
- WEAPVABOECTMGR-UHFFFAOYSA-N triethyl 2-acetyloxypropane-1,2,3-tricarboxylate Chemical compound CCOC(=O)CC(C(=O)OCC)(OC(C)=O)CC(=O)OCC WEAPVABOECTMGR-UHFFFAOYSA-N 0.000 claims description 2
- 239000001069 triethyl citrate Substances 0.000 claims description 2
- VMYFZRTXGLUXMZ-UHFFFAOYSA-N triethyl citrate Natural products CCOC(=O)C(O)(C(=O)OCC)C(=O)OCC VMYFZRTXGLUXMZ-UHFFFAOYSA-N 0.000 claims description 2
- 235000013769 triethyl citrate Nutrition 0.000 claims description 2
- TUUQISRYLMFKOG-UHFFFAOYSA-N trihexyl 2-acetyloxypropane-1,2,3-tricarboxylate Chemical compound CCCCCCOC(=O)CC(C(=O)OCCCCCC)(OC(C)=O)CC(=O)OCCCCCC TUUQISRYLMFKOG-UHFFFAOYSA-N 0.000 claims description 2
- AMMPRZCMKXDUNE-UHFFFAOYSA-N trihexyl 2-hydroxypropane-1,2,3-tricarboxylate Chemical compound CCCCCCOC(=O)CC(O)(C(=O)OCCCCCC)CC(=O)OCCCCCC AMMPRZCMKXDUNE-UHFFFAOYSA-N 0.000 claims description 2
- APVVRLGIFCYZHJ-UHFFFAOYSA-N trioctyl 2-hydroxypropane-1,2,3-tricarboxylate Chemical compound CCCCCCCCOC(=O)CC(O)(C(=O)OCCCCCCCC)CC(=O)OCCCCCCCC APVVRLGIFCYZHJ-UHFFFAOYSA-N 0.000 claims description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 2
- 238000002560 therapeutic procedure Methods 0.000 abstract description 16
- 230000029663 wound healing Effects 0.000 abstract description 2
- 238000005516 engineering process Methods 0.000 description 45
- 239000012530 fluid Substances 0.000 description 20
- 150000001875 compounds Chemical class 0.000 description 11
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 10
- 239000000463 material Substances 0.000 description 10
- 241000283690 Bos taurus Species 0.000 description 9
- 230000001225 therapeutic effect Effects 0.000 description 9
- 210000001519 tissue Anatomy 0.000 description 7
- 150000002148 esters Chemical class 0.000 description 6
- 230000002354 daily effect Effects 0.000 description 5
- 239000000835 fiber Substances 0.000 description 5
- RVRLFABOQXZUJX-UHFFFAOYSA-N 1-[1-(2,5-dioxopyrrol-1-yl)ethyl]pyrrole-2,5-dione Chemical compound O=C1C=CC(=O)N1C(C)N1C(=O)C=CC1=O RVRLFABOQXZUJX-UHFFFAOYSA-N 0.000 description 4
- SGVWDRVQIYUSRA-UHFFFAOYSA-N 1-[2-[2-(2,5-dioxopyrrol-1-yl)ethyldisulfanyl]ethyl]pyrrole-2,5-dione Chemical compound O=C1C=CC(=O)N1CCSSCCN1C(=O)C=CC1=O SGVWDRVQIYUSRA-UHFFFAOYSA-N 0.000 description 4
- FWBHETKCLVMNFS-UHFFFAOYSA-N 4',6-Diamino-2-phenylindol Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC2=CC=C(C(N)=N)C=C2N1 FWBHETKCLVMNFS-UHFFFAOYSA-N 0.000 description 4
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 4
- 102000001187 Collagen Type III Human genes 0.000 description 4
- 108010069502 Collagen Type III Proteins 0.000 description 4
- 102000018233 Fibroblast Growth Factor Human genes 0.000 description 4
- 108050007372 Fibroblast Growth Factor Proteins 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- NXVYSVARUKNFNF-UHFFFAOYSA-N bis(2,5-dioxopyrrolidin-1-yl) 2,3-dihydroxybutanedioate Chemical compound O=C1CCC(=O)N1OC(=O)C(O)C(O)C(=O)ON1C(=O)CCC1=O NXVYSVARUKNFNF-UHFFFAOYSA-N 0.000 description 4
- 238000009826 distribution Methods 0.000 description 4
- ZWIBGKZDAWNIFC-UHFFFAOYSA-N disuccinimidyl suberate Chemical compound O=C1CCC(=O)N1OC(=O)CCCCCCC(=O)ON1C(=O)CCC1=O ZWIBGKZDAWNIFC-UHFFFAOYSA-N 0.000 description 4
- 239000000975 dye Substances 0.000 description 4
- 229940126864 fibroblast growth factor Drugs 0.000 description 4
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 4
- 230000035876 healing Effects 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- 239000002245 particle Substances 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- BBNQQADTFFCFGB-UHFFFAOYSA-N purpurin Chemical compound C1=CC=C2C(=O)C3=C(O)C(O)=CC(O)=C3C(=O)C2=C1 BBNQQADTFFCFGB-UHFFFAOYSA-N 0.000 description 4
- 102000012422 Collagen Type I Human genes 0.000 description 3
- 108010022452 Collagen Type I Proteins 0.000 description 3
- 229930182555 Penicillin Natural products 0.000 description 3
- 150000001720 carbohydrates Chemical class 0.000 description 3
- 239000001913 cellulose Substances 0.000 description 3
- 229920002678 cellulose Polymers 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 239000004020 conductor Substances 0.000 description 3
- 238000010168 coupling process Methods 0.000 description 3
- 238000005859 coupling reaction Methods 0.000 description 3
- 210000000416 exudates and transudate Anatomy 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 230000003647 oxidation Effects 0.000 description 3
- 238000007254 oxidation reaction Methods 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- PVGATNRYUYNBHO-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 4-(2,5-dioxopyrrol-1-yl)butanoate Chemical compound O=C1CCC(=O)N1OC(=O)CCCN1C(=O)C=CC1=O PVGATNRYUYNBHO-UHFFFAOYSA-N 0.000 description 2
- AASBXERNXVFUEJ-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) propanoate Chemical compound CCC(=O)ON1C(=O)CCC1=O AASBXERNXVFUEJ-UHFFFAOYSA-N 0.000 description 2
- RKDVKSZUMVYZHH-UHFFFAOYSA-N 1,4-dioxane-2,5-dione Chemical compound O=C1COC(=O)CO1 RKDVKSZUMVYZHH-UHFFFAOYSA-N 0.000 description 2
- VAZJLPXFVQHDFB-UHFFFAOYSA-N 1-(diaminomethylidene)-2-hexylguanidine Polymers CCCCCCN=C(N)N=C(N)N VAZJLPXFVQHDFB-UHFFFAOYSA-N 0.000 description 2
- RJPSHDMGSVVHFA-UHFFFAOYSA-N 2-[carboxymethyl-[(7-hydroxy-4-methyl-2-oxochromen-8-yl)methyl]amino]acetic acid Chemical compound OC(=O)CN(CC(O)=O)CC1=C(O)C=CC2=C1OC(=O)C=C2C RJPSHDMGSVVHFA-UHFFFAOYSA-N 0.000 description 2
- AXDJCCTWPBKUKL-UHFFFAOYSA-N 4-[(4-aminophenyl)-(4-imino-3-methylcyclohexa-2,5-dien-1-ylidene)methyl]aniline;hydron;chloride Chemical compound Cl.C1=CC(=N)C(C)=CC1=C(C=1C=CC(N)=CC=1)C1=CC=C(N)C=C1 AXDJCCTWPBKUKL-UHFFFAOYSA-N 0.000 description 2
- SGHZXLIDFTYFHQ-UHFFFAOYSA-L Brilliant Blue Chemical compound [Na+].[Na+].C=1C=C(C(=C2C=CC(C=C2)=[N+](CC)CC=2C=C(C=CC=2)S([O-])(=O)=O)C=2C(=CC=CC=2)S([O-])(=O)=O)C=CC=1N(CC)CC1=CC=CC(S([O-])(=O)=O)=C1 SGHZXLIDFTYFHQ-UHFFFAOYSA-L 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 102000009024 Epidermal Growth Factor Human genes 0.000 description 2
- 101800003838 Epidermal growth factor Proteins 0.000 description 2
- 206010063560 Excessive granulation tissue Diseases 0.000 description 2
- 102000003886 Glycoproteins Human genes 0.000 description 2
- 108090000288 Glycoproteins Proteins 0.000 description 2
- 102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 2
- 108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 2
- KQHKSGRIBYJYFX-UHFFFAOYSA-J Ponceau S Chemical compound [Na+].[Na+].[Na+].[Na+].Oc1c(cc2cc(ccc2c1N=Nc1ccc(cc1S([O-])(=O)=O)N=Nc1ccc(cc1)S([O-])(=O)=O)S([O-])(=O)=O)S([O-])(=O)=O KQHKSGRIBYJYFX-UHFFFAOYSA-J 0.000 description 2
- 241000206607 Porphyra umbilicalis Species 0.000 description 2
- PLXBWHJQWKZRKG-UHFFFAOYSA-N Resazurin Chemical compound C1=CC(=O)C=C2OC3=CC(O)=CC=C3[N+]([O-])=C21 PLXBWHJQWKZRKG-UHFFFAOYSA-N 0.000 description 2
- FHNINJWBTRXEBC-UHFFFAOYSA-N Sudan III Chemical compound OC1=CC=C2C=CC=CC2=C1N=NC(C=C1)=CC=C1N=NC1=CC=CC=C1 FHNINJWBTRXEBC-UHFFFAOYSA-N 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 230000003115 biocidal effect Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000002041 carbon nanotube Substances 0.000 description 2
- 229910021393 carbon nanotube Inorganic materials 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 229940096422 collagen type i Drugs 0.000 description 2
- 229920001577 copolymer Polymers 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- WFPZPJSADLPSON-UHFFFAOYSA-N dinitrogen tetraoxide Chemical compound [O-][N+](=O)[N+]([O-])=O WFPZPJSADLPSON-UHFFFAOYSA-N 0.000 description 2
- RAGZEDHHTPQLAI-UHFFFAOYSA-L disodium;2',4',5',7'-tetraiodo-3-oxospiro[2-benzofuran-1,9'-xanthene]-3',6'-diolate Chemical compound [Na+].[Na+].O1C(=O)C2=CC=CC=C2C21C1=CC(I)=C([O-])C(I)=C1OC1=C(I)C([O-])=C(I)C=C21 RAGZEDHHTPQLAI-UHFFFAOYSA-L 0.000 description 2
- 229940116977 epidermal growth factor Drugs 0.000 description 2
- 230000014509 gene expression Effects 0.000 description 2
- 210000001126 granulation tissue Anatomy 0.000 description 2
- 239000003102 growth factor Substances 0.000 description 2
- 229960003988 indigo carmine Drugs 0.000 description 2
- KHLVKKOJDHCJMG-QDBORUFSSA-L indigo carmine Chemical compound [Na+].[Na+].N/1C2=CC=C(S([O-])(=O)=O)C=C2C(=O)C\1=C1/NC2=CC=C(S(=O)(=O)[O-])C=C2C1=O KHLVKKOJDHCJMG-QDBORUFSSA-L 0.000 description 2
- 235000012738 indigotine Nutrition 0.000 description 2
- 239000004179 indigotine Substances 0.000 description 2
- MOFVSTNWEDAEEK-UHFFFAOYSA-M indocyanine green Chemical compound [Na+].[O-]S(=O)(=O)CCCCN1C2=CC=C3C=CC=CC3=C2C(C)(C)C1=CC=CC=CC=CC1=[N+](CCCCS([O-])(=O)=O)C2=CC=C(C=CC=C3)C3=C2C1(C)C MOFVSTNWEDAEEK-UHFFFAOYSA-M 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- DWCZIOOZPIDHAB-UHFFFAOYSA-L methyl green Chemical compound [Cl-].[Cl-].C1=CC(N(C)C)=CC=C1C(C=1C=CC(=CC=1)[N+](C)(C)C)=C1C=CC(=[N+](C)C)C=C1 DWCZIOOZPIDHAB-UHFFFAOYSA-L 0.000 description 2
- CXKWCBBOMKCUKX-UHFFFAOYSA-M methylene blue Chemical compound [Cl-].C1=CC(N(C)C)=CC2=[S+]C3=CC(N(C)C)=CC=C3N=C21 CXKWCBBOMKCUKX-UHFFFAOYSA-M 0.000 description 2
- 229960000907 methylthioninium chloride Drugs 0.000 description 2
- SHXOKQKTZJXHHR-UHFFFAOYSA-N n,n-diethyl-5-iminobenzo[a]phenoxazin-9-amine;hydrochloride Chemical compound [Cl-].C1=CC=C2C3=NC4=CC=C(N(CC)CC)C=C4OC3=CC(=[NH2+])C2=C1 SHXOKQKTZJXHHR-UHFFFAOYSA-N 0.000 description 2
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 2
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 2
- 229960005489 paracetamol Drugs 0.000 description 2
- 150000002960 penicillins Chemical class 0.000 description 2
- GVKCHTBDSMQENH-UHFFFAOYSA-L phloxine B Chemical compound [Na+].[Na+].[O-]C(=O)C1=C(Cl)C(Cl)=C(Cl)C(Cl)=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C([O-])=C(Br)C=C21 GVKCHTBDSMQENH-UHFFFAOYSA-L 0.000 description 2
- OXNIZHLAWKMVMX-UHFFFAOYSA-N picric acid Chemical compound OC1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-N 0.000 description 2
- 239000004175 ponceau 4R Substances 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 230000000069 prophylactic effect Effects 0.000 description 2
- INCIMLINXXICKS-UHFFFAOYSA-M pyronin Y Chemical compound [Cl-].C1=CC(=[N+](C)C)C=C2OC3=CC(N(C)C)=CC=C3C=C21 INCIMLINXXICKS-UHFFFAOYSA-M 0.000 description 2
- NDVLTYZPCACLMA-UHFFFAOYSA-N silver oxide Chemical compound [O-2].[Ag+].[Ag+] NDVLTYZPCACLMA-UHFFFAOYSA-N 0.000 description 2
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 description 2
- RWVGQQGBQSJDQV-UHFFFAOYSA-M sodium;3-[[4-[(e)-[4-(4-ethoxyanilino)phenyl]-[4-[ethyl-[(3-sulfonatophenyl)methyl]azaniumylidene]-2-methylcyclohexa-2,5-dien-1-ylidene]methyl]-n-ethyl-3-methylanilino]methyl]benzenesulfonate Chemical compound [Na+].C1=CC(OCC)=CC=C1NC1=CC=C(C(=C2C(=CC(C=C2)=[N+](CC)CC=2C=C(C=CC=2)S([O-])(=O)=O)C)C=2C(=CC(=CC=2)N(CC)CC=2C=C(C=CC=2)S([O-])(=O)=O)C)C=C1 RWVGQQGBQSJDQV-UHFFFAOYSA-M 0.000 description 2
- 150000003431 steroids Chemical class 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 229940041022 streptomycins Drugs 0.000 description 2
- 229960002317 succinimide Drugs 0.000 description 2
- 229940099373 sudan iii Drugs 0.000 description 2
- 230000008467 tissue growth Effects 0.000 description 2
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 2
- PAPBSGBWRJIAAV-UHFFFAOYSA-N ε-Caprolactone Chemical compound O=C1CCCCCO1 PAPBSGBWRJIAAV-UHFFFAOYSA-N 0.000 description 2
- ZXSQEZNORDWBGZ-UHFFFAOYSA-N 1,3-dihydropyrrolo[2,3-b]pyridin-2-one Chemical compound C1=CN=C2NC(=O)CC2=C1 ZXSQEZNORDWBGZ-UHFFFAOYSA-N 0.000 description 1
- JKFYKCYQEWQPTM-UHFFFAOYSA-N 2-azaniumyl-2-(4-fluorophenyl)acetate Chemical compound OC(=O)C(N)C1=CC=C(F)C=C1 JKFYKCYQEWQPTM-UHFFFAOYSA-N 0.000 description 1
- YELWNIMQOUETBV-UHFFFAOYSA-N 4-azido-2-hydroxy-n-[2-(pyridin-2-yldisulfanyl)ethyl]benzamide Chemical compound OC1=CC(N=[N+]=[N-])=CC=C1C(=O)NCCSSC1=CC=CC=N1 YELWNIMQOUETBV-UHFFFAOYSA-N 0.000 description 1
- YAMJITULHOEKMI-UHFFFAOYSA-N B([O-])([O-])[O-].[Ag+3] Chemical compound B([O-])([O-])[O-].[Ag+3] YAMJITULHOEKMI-UHFFFAOYSA-N 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- GHXZTYHSJHQHIJ-UHFFFAOYSA-N Chlorhexidine Chemical compound C=1C=C(Cl)C=CC=1NC(N)=NC(N)=NCCCCCCN=C(N)N=C(N)NC1=CC=C(Cl)C=C1 GHXZTYHSJHQHIJ-UHFFFAOYSA-N 0.000 description 1
- 102000000503 Collagen Type II Human genes 0.000 description 1
- 108010041390 Collagen Type II Proteins 0.000 description 1
- 206010056340 Diabetic ulcer Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 208000004210 Pressure Ulcer Diseases 0.000 description 1
- 229910021607 Silver chloride Inorganic materials 0.000 description 1
- 229910021612 Silver iodide Inorganic materials 0.000 description 1
- 208000000558 Varicose Ulcer Diseases 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000002390 adhesive tape Substances 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 229940064734 aminobenzoate Drugs 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 230000002421 anti-septic effect Effects 0.000 description 1
- 108010045569 atelocollagen Proteins 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 229940096423 bovine collagen type i Drugs 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 125000002843 carboxylic acid group Chemical group 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 229960003260 chlorhexidine Drugs 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 239000003431 cross linking reagent Substances 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- KXGVEGMKQFWNSR-LLQZFEROSA-M deoxycholate Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC([O-])=O)C)[C@@]2(C)[C@@H](O)C1 KXGVEGMKQFWNSR-LLQZFEROSA-M 0.000 description 1
- 229940009976 deoxycholate Drugs 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- KZNICNPSHKQLFF-UHFFFAOYSA-N dihydromaleimide Natural products O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- OJKANDGLELGDHV-UHFFFAOYSA-N disilver;dioxido(dioxo)chromium Chemical compound [Ag+].[Ag+].[O-][Cr]([O-])(=O)=O OJKANDGLELGDHV-UHFFFAOYSA-N 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 210000002615 epidermis Anatomy 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 238000001125 extrusion Methods 0.000 description 1
- 230000004907 flux Effects 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 230000002706 hydrostatic effect Effects 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 125000000468 ketone group Chemical group 0.000 description 1
- 150000002576 ketones Chemical group 0.000 description 1
- 150000002596 lactones Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 238000009581 negative-pressure wound therapy Methods 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 206010033675 panniculitis Diseases 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 125000000075 primary alcohol group Chemical group 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000003385 ring cleavage reaction Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 238000007493 shaping process Methods 0.000 description 1
- ZHFGZPALNGKPQZ-UHFFFAOYSA-M silver 2-aminooxybenzoate Chemical compound [Ag+].NOc1ccccc1C([O-])=O ZHFGZPALNGKPQZ-UHFFFAOYSA-M 0.000 description 1
- NBYLLBXLDOPANK-UHFFFAOYSA-M silver 2-carboxyphenolate hydrate Chemical compound C1=CC=C(C(=C1)C(=O)O)[O-].O.[Ag+] NBYLLBXLDOPANK-UHFFFAOYSA-M 0.000 description 1
- CQLFBEKRDQMJLZ-UHFFFAOYSA-M silver acetate Chemical compound [Ag+].CC([O-])=O CQLFBEKRDQMJLZ-UHFFFAOYSA-M 0.000 description 1
- 229940071536 silver acetate Drugs 0.000 description 1
- ADZWSOLPGZMUMY-UHFFFAOYSA-M silver bromide Chemical compound [Ag]Br ADZWSOLPGZMUMY-UHFFFAOYSA-M 0.000 description 1
- LKZMBDSASOBTPN-UHFFFAOYSA-L silver carbonate Substances [Ag].[O-]C([O-])=O LKZMBDSASOBTPN-UHFFFAOYSA-L 0.000 description 1
- 229910001958 silver carbonate Inorganic materials 0.000 description 1
- 229940071575 silver citrate Drugs 0.000 description 1
- 229940045105 silver iodide Drugs 0.000 description 1
- HKZLPVFGJNLROG-UHFFFAOYSA-M silver monochloride Chemical compound [Cl-].[Ag+] HKZLPVFGJNLROG-UHFFFAOYSA-M 0.000 description 1
- 229910001961 silver nitrate Inorganic materials 0.000 description 1
- 229910001923 silver oxide Inorganic materials 0.000 description 1
- YPNVIBVEFVRZPJ-UHFFFAOYSA-L silver sulfate Chemical compound [Ag+].[Ag+].[O-]S([O-])(=O)=O YPNVIBVEFVRZPJ-UHFFFAOYSA-L 0.000 description 1
- 229910000367 silver sulfate Inorganic materials 0.000 description 1
- LMEWRZSPCQHBOB-UHFFFAOYSA-M silver;2-hydroxypropanoate Chemical compound [Ag+].CC(O)C([O-])=O LMEWRZSPCQHBOB-UHFFFAOYSA-M 0.000 description 1
- MNMYRUHURLPFQW-UHFFFAOYSA-M silver;dodecanoate Chemical compound [Ag+].CCCCCCCCCCCC([O-])=O MNMYRUHURLPFQW-UHFFFAOYSA-M 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- MIDXXTLMKGZDPV-UHFFFAOYSA-M sodium;1-[6-(2,5-dioxopyrrol-1-yl)hexanoyloxy]-2,5-dioxopyrrolidine-3-sulfonate Chemical compound [Na+].O=C1C(S(=O)(=O)[O-])CC(=O)N1OC(=O)CCCCCN1C(=O)C=CC1=O MIDXXTLMKGZDPV-UHFFFAOYSA-M 0.000 description 1
- GGCZERPQGJTIQP-UHFFFAOYSA-N sodium;9,10-dioxoanthracene-2-sulfonic acid Chemical compound [Na+].C1=CC=C2C(=O)C3=CC(S(=O)(=O)O)=CC=C3C(=O)C2=C1 GGCZERPQGJTIQP-UHFFFAOYSA-N 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 210000004304 subcutaneous tissue Anatomy 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- QUTYHQJYVDNJJA-UHFFFAOYSA-K trisilver;2-hydroxypropane-1,2,3-tricarboxylate Chemical compound [Ag+].[Ag+].[Ag+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O QUTYHQJYVDNJJA-UHFFFAOYSA-K 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/42—Use of materials characterised by their function or physical properties
-
- A61F13/01012—
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/22—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
- A61L15/225—Mixtures of macromolecular compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/22—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
- A61L15/28—Polysaccharides or their derivatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/22—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
- A61L15/32—Proteins, polypeptides; Degradation products or derivatives thereof, e.g. albumin, collagen, fibrin, gelatin
- A61L15/325—Collagen
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/42—Use of materials characterised by their function or physical properties
- A61L15/46—Deodorants or malodour counteractants, e.g. to inhibit the formation of ammonia or bacteria
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/42—Use of materials characterised by their function or physical properties
- A61L15/64—Use of materials characterised by their function or physical properties specially adapted to be resorbable inside the body
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/20—Polysaccharides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
- A61L27/24—Collagen
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/26—Mixtures of macromolecular compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/54—Biologically active materials, e.g. therapeutic substances
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/58—Materials at least partially resorbable by the body
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
- A61M1/90—Negative pressure wound therapy devices, i.e. devices for applying suction to a wound to promote healing, e.g. including a vacuum dressing
- A61M1/91—Suction aspects of the dressing
- A61M1/915—Constructional details of the pressure distribution manifold
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/10—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing inorganic materials
- A61L2300/102—Metals or metal compounds, e.g. salts such as bicarbonates, carbonates, oxides, zeolites, silicates
- A61L2300/104—Silver, e.g. silver sulfadiazine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/404—Biocides, antimicrobial agents, antiseptic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
- A61M1/90—Negative pressure wound therapy devices, i.e. devices for applying suction to a wound to promote healing, e.g. including a vacuum dressing
- A61M1/92—Negative pressure wound therapy devices, i.e. devices for applying suction to a wound to promote healing, e.g. including a vacuum dressing with liquid supply means
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
- A61M1/90—Negative pressure wound therapy devices, i.e. devices for applying suction to a wound to promote healing, e.g. including a vacuum dressing
- A61M1/94—Negative pressure wound therapy devices, i.e. devices for applying suction to a wound to promote healing, e.g. including a vacuum dressing with gas supply means
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M35/00—Devices for applying media, e.g. remedies, on the human body
Definitions
- the present technology relates generally to wound inserts and methods for facilitating wound healing. Methods of use, methods for manufacture, and kits for use in practicing the methods are also provided.
- dressings A wide variety of materials and devices, generally characterized as“dressings,” are generally known in the art for use in treating an injury or other disruption of tissue. Such wounds may be the result of trauma, surgery, or disease, and may affect skin or other tissues. In general, dressings may control bleeding, absorb wound exudate, ease pain, assist in debriding the wound, protect wound tissue from infection, or otherwise promote healing and protect the wound from further damage.
- a wound insert in an aspect, includes an outer layer and an inner core.
- the outer layer includes a photocrosslinked biopolymer, a reagent-crosslinked biopolymer, or both (collectively,“crosslinked biopolymer”), and the inner core includes a biopolymer. Further, the outer layer exhibits a modulus of elasticity from about 0.5 MPa to about 5.0 MPa; and the inner core exhibits a lower modulus of elasticity.
- a method for treating a wound in a subject includes administering a wound insert of any embodiment disclosed herein to the wound.
- kits that includes a wound insert of any embodiment disclosed herein as well as instructions for use.
- a method of manufacturing a wound insert of any embodiment of the present technology includes fabricating an outer layer of the wound insert from a first slurry comprising one or more biopolymers, wherein the outer layer is in a shape having a hollow center; photo-crosslinking and/or reagent crosslinking the outer layer to obtain one or more photocrosslinked and/or reagent- crosslinked biopolymers; drying the outer layer of the wound insert; depositing a second slurry into the hollow center of the outer layer to form an inner core of the wound insert; and removing residual moisture from the inner core, where the shape of the outer layer may be a cylinder, a sphere, a cube, a cuboid, a hexagonal prism, a cone, a square-based pyramid, triangular-based pyramid, or a triangular prism; the second slurry includes a biopolymer; the outer layer exhibits a modulus of elasticity from about 0.5 MP
- FIGs. 1 A-1B show cross-sectional views of a diagrammatic representation of an embodiment of an insert of the present technology having a cylindrical shape.
- FIGs. 2A-2B show cross-sectional views of a diagrammatic representation of an embodiment of an insert of the present technology having a cuboidal shape with rounded edges.
- FIG. 3 shows a cross-sectional view of a diagrammatic representation of an embodiment of an insert of the present technology having a cuboidal shape with rounded edges and perforations in the outer layer.
- FIG. 4 shows a cross-sectional view of a diagrammatic representation of an embodiment of an insert of the present technology having a cuboidal shape with rounded edges and though-holes.
- “about” will be understood by persons of ordinary skill in the art and will vary to some extent depending upon the context in which it is used. If there are uses of the term which are not clear to persons of ordinary skill in the art, given the context in which it is used,“about” will mean up to plus or minus 10% of the particular term - for example,“about 10 wt.%” would mean“9 wt.% to 11 wt.%.” It is to be understood that when“about” precedes a term, the term is to be construed as disclosing“about” the term as well as the term without modification by“about” - for example,“about 10 wt.%” discloses “9 wt.% to 11 wt.%” as well as discloses“10 wt.%.”
- modulus of elasticity refers to the measure of an object or a substance’s resistance to being deformed elastically (i.e., non-permanently) upon the application of a stress.
- modulus of elasticity of an object is defined by the following formula:
- the term“radiant power” or“irradiance” refers to the radiant flux or power received by a surface (e.g., a biopolymer of an outer layer of a wound insert as disclosed herein) per unit area.
- the SI unit of irradiance is the watt per square meter (W/m 2 ).
- the“administration” of a wound insert to a subject includes any route of introducing or delivering to a subject a wound insert to perform its intended function. Administration can be carried out by any suitable route, including, but not limited to, topical administration. Administration includes self-administration and the administration by another.
- the term“effective amount” refers to a quantity sufficient to achieve a desired therapeutic and/or prophylactic effect, e.g, an amount which results in the decrease in a wound described herein or one or more signs or symptoms associated with a wound described herein.
- the amount of an insert administered to the subject will vary depending on the composition, the degree, type, and severity of the wound and on the characteristics of the individual.
- the inserts can also be administered in combination with one or more additional therapeutic compounds.
- the therapeutic inserts may be administered to a subject having one or more wounds.
- the terms“individual”,“patient”, or“subject” can refer to an individual organism, a vertebrate, a mammal, or a human. In some embodiments, the individual, patient, or subject is a human.
- Treating” or“treatment” as used herein covers the treatment of a wound described herein, in a subject, such as a human, and includes: (i) inhibiting a wound, i.e., arresting its development; (ii) relieving a wound, i.e., causing regression of the wound; (iii) slowing progression of the wound; and/or (iv) inhibiting, relieving, or slowing progression of one or more symptoms of the wound.
- treatment means that the symptoms associated with the wound are alleviated, reduced, cured, or placed in a state of remission.
- the various modes of treatment of wounds as described herein are intended to mean“substantial,” which includes total but also less than total treatment, and wherein some biologically or medically relevant result is achieved.
- the treatment may be a continuous prolonged treatment for a chronic wound or a single administration, or a few administrations for the treatment of an acute wound.
- a lengthy tunneling wound can be very challenging to heal since such wounds do not respond to mainstream wound care treatment. Such wounds can not only lead to chronic wound formation, but also patient mortality.
- the present disclosure is directed to wound inserts that include an outer layer and an inner core of biologically-active biopolymers.
- the wound inserts of the present technology advantageously may exhibit reduced wound packing pressure on the sides of the wound tunnel and may decrease bioburden due to antimicrobial properties of the wound insert.
- the wound insert of the present technology may further help prevent the collapse of the wound.
- the components of the wound insert may stimulate tissue growth and/or prevent bacterial infection.
- the components of the wound insert may reduce the inflammatory phase, may stimulate granulation tissue growth, and/or may reduce bacterial bioburden.
- the wound insert of the present technology may further be configured, due to the nature of the outer layer, with a bioresorbable suture thread to facilitate removal of the wound insert for wound assessment.
- a wound insert in an aspect, includes an outer layer and an inner core.
- the outer layer includes a crosslinked biopolymer, such as a photocrosslinked biopolymer, a reagent-crosslinked biopolymer, or both, and the inner core includes a biopolymer.
- the outer layer exhibits a modulus of elasticity from about 0.5 MPa to about 5.0 MPa; and the inner core exhibits a lower modulus of elasticity.
- the outer layer of any embodiment disclosed herein may exhibit a modulus of elasticity of about 0.5 MPa, about 0.6 MPa, about 0.7 MPa, about 0.8 MPa, about 0.9 MPa, about 1.0 MPa, about 1.3 MPa, about 1.4 MPa, about 1.5 MPa, about 1.6 MPa, about 1.7 MPa, about 1.8 MPa, about 1.9 MPa, about 2.0 MPa, about 2.1 MPa, about 2.2 MPa, about 2.3 MPa, about 2.4 MPa, about 2.5 MPa, about 2.6 MPa, about 2.7 MPa, about 2.8 MPa, about 2.9 MPa, about 3.0 MPa, about 3.1 MPa, about 3.2 MPa, about 3.3 MPa, about 3.4 MPa, about 3.5 MPa, about 3.6 MPa, about 3.7 MPa, about 3.8 MPa, about 3.9 MPa, about 4.0 MPa, about 4.1 MPa, about 4.2 MPa, about 4.3 MPa, about 4.4 MPa, about 4.5 MPa, about 4.6 MP
- the inner core exhibits a lower modulus of elasticity than the outer layer.
- the inner core may exhibit a modulus of elasticity of about 0.0 MPa, about 0.1 MPa, about 0.2 MPa, about 0.3 MPa, about 0.5 MPa, or any range including and/or in between any two of these values.
- FIGs. 1 A-1B and 2A-2B provide non-limiting representative illustrations of embodiments of a wound insert of the present technology, illustrating the outer layer (101 and 201, respectively) and of the inner core (102 and 202, respectively) of such a wound insert.
- FIG. 1 A provides an illustrative side view illustration of a wound insert 100 having a cylindrical shape that includes an outer layer 101 and an inner core 102.
- FIG. IB provides an illustrative cross-sectional view of the wound insert 100 having a cylindrical shape.
- FIG. 2 A provides an illustrative side view illustration of a wound insert 200 having a cuboidal shape with rounded edges that includes an outer layer 201 and an inner core 202.
- FIG. 2B provides an illustrative cross-sectional view illustration of the wound insert 200 having a cuboidal shape with rounded edges.
- the outer layer may include an inner core facing side and a side facing away from the inner core (i.e., outer facing side).
- the outer facing side of the outer layer may be configured to be in contact with a wound when in use.
- the outer layer envelopes the inner core.
- the wound insert may further include a suture thread connected to and extending from the outer layer and advantageously allowing for the removal of the wound insert if, for example, such removal is desired to assess the healing progress of a wound.
- the suture thread may be a bioresorbable suture thread.
- Bioresorbable suture thread materials include, but are not limited to, a poly(glycolic acid), a poliglycaprone (a copolymer of glycolide and a caprolactone, such as a copolymer of glycolide and e- caprolactone), a polydioxanone, a collagen, or a combination of any two or more thereof.
- Suture threads of any embodiment herein may be monofilament or polyfilament suture threads, where polyfilament suture threads may be braided.
- the length of the suture thread as measured extending from the outer layer may be about 0.1 centimeters (cm) to about 10 cm.
- the thickness of the outer layer of any embodiment herein may be about 20 mM to about 300 mM
- the thickness of the outer layer may be about 20 mM, about 22 mM, about 24 mM, about 26 mM, about 28 mM, about 30 mM, about 32 mM, about 34 mM, about 36 mM, about 38 mM, about 40 mM, about 42 mM, about 44 mM, about 46 mM, about 48 mM, about 50 mM, about 55 mM, about 60 mM, about 65 mM, about 70 mM, about 75 mM, about 80 mM, about 85 mM, about 90 mM, about 95 mM, about 100 mM, about 110 mM, about 120 mM, about 130 mM, about 140 mM, about 150 mM, about 160 mM, about 170 mM, about 180 mM, about 190 mM, about 200 mM
- the crosslinked biopolymer of the outer layer may include a collagen, an oxidized cellulose, an oxidized regenerated cellulose (ORC), a polysaccharide, chitosan, gelatin, hyaluronic acid, or a combination of any two or more thereof.
- the outer layer may include about 0.01 wt.% to 100 wt.% of crosslinked biopolymer.
- the outer layer may include crosslinked biopolymer in an amount (based on the total weight of the outer layer) of about 0.01 wt.%, about 0.1 wt.%, about 1 wt.%, about 2 wt.%, about 3 wt.%, about 4 wt.%, about 5 wt.%, about 6 wt.%, about 7 wt.%, about 8 wt.%, about 9 wt.%, about 10 wt.%, about 12 wt.%, about 14 wt.%, about 16 wt.%, about 18 wt.%, about 20 wt.%, about 25 wt.%, about 30 wt.%, about 35 wt.%, about 40 wt.%, about 45 wt.%, about 50 wt.%, about 55 wt.%, about 60 wt.%, about 65 wt.%, about 70 wt.%, about 75 wt.%, about
- the outer layer may include from about 50 wt.% to about 100 wt.% gelatin. In any embodiment herein, the outer layer may include collagen and ORC. In any embodiment herein, the outer layer may include collagen, ORC, and gelatin.
- Photocrosslinked biopolymers are to be understood as biopolymers that have been crosslinked due to light and that do not include a cross-linking compound (cross-linking compounds are used to produce the reagent-crosslinked biopolymers, as discussed herein).
- the photocrosslinked biopolymer of the outer layer may be produced from a biopolymer that is photocrosslinked by exposure to light with a wavelength from about 360 nm to about 370 nm.
- the total radiant power of all wavelengths of light used to crosslink the biopolymer of the outer layer may be from about 10 mW/cm 2 to about 1000 mW/cm 2 .
- the total radiant power of all wavelengths of light used to crosslink the biopolymer of the outer layer may be from about 10 mW/cm 2 , about 15 mW/cm 2 , about 20 mW/cm 2 , about 25 mW/cm 2 , about 30 mW/cm 2 , about 35 mW/cm 2 , about 40 mW/cm 2 , about 45 mW/cm 2 , about 50 mW/cm 2 , about 55 mW/cm 2 , about 60 mW/cm 2 , about 65 mW/cm 2 , about 70 mW/cm 2 , about 75 mW/cm 2 , about 80 mW/cm 2 , about 85 mW/cm 2 , about 90 mW/cm 2 , about 95 mW/cm 2 , about 100 mW/cm 2 , about 110 mW/cm 2 , about 120 mW/cm
- Reagent-crosslinked biopolymer are biopolymers that are crosslinked via cross- linking compounds where part of the cross-linking compound is incorporated to generate the reagent-crosslinked biopolymer.
- Exemplary reagent-crosslinked biopolymers are
- DSS disuccinimidyl suberate
- DST disuccinimidyl tartrate
- DSP dithiobis succinimidy
- exemplary reagent-crosslinked biopolymers are biopolymers crosslinked in the presence of light (e.g ., 250-350 nm light) with A-((2-pyridyldithio)ethyl)-4- azidosalicylamide and/or A-5-azido-2-nitrobenzyloxysuccinimide - thus, light may be used to initiate the crosslinking reaction of the cross-linking compound with a biopolymer.
- light e.g ., 250-350 nm light
- light may be used to initiate the crosslinking reaction of the cross-linking compound with a biopolymer.
- the outer layer may include at least one plasticizer.
- the at least one plasticizer may be included in the amount of about 2 wt.% to about 30 wt.% within the outer layer.
- the at least one plasticizer may be included in the amount of about 2 wt.%, about 3 wt.%, about 4 wt.%, about 5 wt.%, about 6 wt.%, about 7 wt.%, about 8 wt.%, about 9 wt.%, about 10 wt.%, about 11 wt.%, about 12 wt.%, about 13 wt.%, about 14 wt.%, about 15 wt.%, about 16 wt.%, about 17 wt.%, about 18 wt.%, about 19 wt.%, about 20 wt.%, about 21 wt.%, about 22 wt.%, about 23 wt.%, about 24 wt.%, about
- Exemplary plasticizers include, but are not limited to, an acetylated monoglyceride, an alkyl citrate, methyl ricinoleate, glycerol, or a combination of any two or more thereof.
- alkyl citrates include, but are not limited to, triethyl citrate, acetyl triethyl citrate, tributyl citrate, acetyl tributyl citrate, trioctyl citrate, acetyl trioctyl citrate, trihexyl citrate, acetyl trihexyl citrate, butyryl trihexyl citrate, trimethyl citrate, or a combination of any two or more thereof.
- the outer layer may include one or more additional materials.
- additional materials may include, but are not limited to, biocompatible dyes, non— steroidal anti-inflammatory drug (e.g ., acetaminophen), hyaluronic acid, a steroid, an antibiotic (e.g., penicillins and/or streptomycins), glycoproteins (e.g, lipids), growth factors (e.g, fibroblast growth factor (FGF), an epidermal growth factor (RGF), a platelet derived growth factor (PGDF)), or a combination of any two or more thereof.
- non— steroidal anti-inflammatory drug e.g ., acetaminophen
- hyaluronic acid e.g., hyaluronic acid
- a steroid e.g., an antibiotic (e.g., penicillins and/or streptomycins), glycoproteins (e.g, lipids), growth factors (e.g, fibroblast growth factor (
- the biocompatible dye may include, but is not limited to, E124, fluorescein isothiocyanate (FITC), 4’,6-diamidino-2-phenylindole (DAPI), methylene blue, erythrosine B, ponceau S, alura red, SYBR green, alcian blue, brilliant blue G, calcein blue, cardio green, crystal violet, nile blue, india ink, brilliant blue, indigo carmine, Sudan III, methyl green, oil red, pyronin Y, tattoo ink, purpurin, phloxine B, picric acid, carbon nanotubes, a fuchsin, resazurin, a trichrome, or a combination of any two or more thereof.
- FITC fluorescein isothiocyanate
- DAPI 6-diamidino-2-phenylindole
- the inner core may include a wound-facing side.
- the biopolymer of the inner core may be a collagen, an oxidized cellulose, and oxidized regenerated cellulose (ORC), a polysaccharide, chitosan, gelatin, hyaluronic acid, or a combination of any two or more thereof.
- ORC oxidized regenerated cellulose
- the inner core may include about 10 wt.% to about 100 wt.% of the biopolymer; thus, the inner core may include the biopolymer at an amount (based on the weight of the inner core) of about 10 wt.%, about 15 wt.%, about 20 wt.%, about 25 wt.%, about 30 wt.%, about 35 wt.%, about 40 wt.%, about 45 wt.%, about 50 wt.%, about 55 wt.%, about 60 wt.%, about 65 wt.%, about 70 wt.%, about 75 wt.%, about 80 wt.%, about 85 wt.%, about 90 wt.%, about 95 wt.%, about 99 wt.%, about 100 wt.%, or any range including and/or in between any two of these values.
- the inner core may include less than about 0.01 wt.% of crosslinked biopoly
- the inner core may include one or more additional materials.
- additional materials may include, but are not limited to, biocompatible dyes, non— steroidal anti-inflammatory drug (e.g, acetaminophen), hyaluronic acid, a steroid, an antibiotic (e.g, penicillins and/or streptomycins), glycoproteins (e.g, lipids), growth factors (e.g, fibroblast growth factor (FGF), an epidermal growth factor (RGF), a platelet derived growth factor (PGDF)), or a combination of any two or more thereof.
- non— steroidal anti-inflammatory drug e.g, acetaminophen
- hyaluronic acid e.g, hyaluronic acid
- a steroid e.g, an antibiotic (e.g, penicillins and/or streptomycins)
- glycoproteins e.g, lipids
- growth factors e.g, fibroblast growth factor (FGF), an epi
- the biocompatible dye may include, but is not limited to, E124, fluorescein isothiocyanate (FITC), 4’,6-diamidino-2-phenylindole (DAPI), methylene blue, erythrosine B, ponceau S, alura red, SYBR green, alcian blue, brilliant blue G, calcein blue, cardio green, crystal violet, nile blue, india ink, brilliant blue, indigo carmine, Sudan III, methyl green, oil red, pyronin Y, tattoo ink, purpurin, phloxine B, picric acid, carbon nanotubes, a fuchsin, resazurin, a trichrome, or a combination of any two or more thereof.
- FITC fluorescein isothiocyanate
- DAPI 6-diamidino-2-phenylindole
- the inner core may further include powders, porous matrices, or combinations thereof.
- powders in any embodiment herein, for example, may include freeze-dried collagen/ORC in powder form.
- porous matrix materials may include a freeze-dried collagen/ORC matrix.
- the collagen of the outer layer and/or the inner core may include a mammalian collagen, such as a bovine collagen, a human collagen, or a combination thereof.
- the collagen of any embodiment herein may be a Type I collagen, a Type II collagen, a Type III collagen, may be obtained from any natural source, may be chemically-modified collagen (e.g ., an atelocollagen obtained by removing the immunogenic telopeptides from natural collagen), or may be a combination of any two or more thereof.
- the collagen may include collagen obtained from bovine corium that has been rendered largely free of non-collagenous components, for example, including fat, non- collagenous proteins, polysaccharides, and other carbohydrates, such as by procedures described in U.S. Pat. Nos. 4,614,794 and 4,320,201, each of which is incorporated herein by reference.
- the bovine collagen may include one or both of bovine collagen type I and bovine collagen type III.
- the outer layer and/or inner core may include a weight ratio of human collagen type I to human collagen type III of about 100:0, about 90: 10, about 80:20, about 70:30, about 60:40, about 50:50, about 40:60, about 30:70, about 20:80, about 10:90, about 0: 100, or any range including and/or in between any two of these values.
- the ratio by weight of human collagen type I to human collagen type III may be greater than about 50:50, or greater than about 70:30.
- the collagen of any embodiment herein may include a weight ratio of type I bovine collagen to type III bovine collagen of about 95:5, about 85: 15, about 75:25, about 65:35, about 55:45, about 50:50, about 45:55, about 65:35, about 75:25, about 85: 15, about 95:5, or any range including and/or in between any two of these values.
- the ratio by weight of the type I bovine collagen to type III bovine collagen may be about 85: 15.
- the amount of collagen included in the outer layer and/or the inner core of any embodiment herein may be about 30 wt.% to 100 wt.%.
- the amount of collagen may be about 30 wt.%, about 32 wt.%, about 34 wt.%, about 36 wt.%, about 38 wt.%, about 40 wt.%, about 42 wt.%, about 44 wt.%, about 46 wt.%, about 48 wt.%, about 50 wt.%, about 52 wt.%, about 54 wt.%, about 56 wt.%, about 58 wt.%, about 60 wt.%, about 62 wt.%, about 64 wt.%, about 66 wt.%, about 68 wt.%, about 70 wt.%, about 72 wt.%, about 74 wt.%, about 76 wt.%, about 78 wt.%
- the collagen included in the outer layer and/or the inner core of any embodiment herein may have a weight-average molecular weight of about 5,000, about 6,000, about 7,000, about 8,000, about 9,000, about 10,000, about 12,000, about 14,000, about 16,000, about 18,000, about 20,000, about 22,000, about 24,000, about 26,000, about 28,000, about 30,000, about 32,000, about 34,000, about 36,000, about 38,000, about 40,000, about 45,000, about 50,000, about 55,000, about 60,000, about 65,000, about 70,000, about 75,000, about 80,000, about 85,000, about 90,000, about 95,000, about 100,000, or any range including and/or in between any two of these values.
- the outer layer and/or the inner core may include ORC.
- ORC may be produced by the oxidation of cellulose, for example with dinitrogen tetroxide and/or as described in U.S. Pat. No. 3,122,479 (incorporated herein by reference). Not intending to be bound by theory, it is believed that this process may convert primary alcohol groups on the saccharide residues of the cellulose to carboxylic acid groups, for example, forming uronic acid residues within the cellulose chain. The oxidation may not proceed with complete selectivity, and as a result hydroxyl groups on carbons 2 and 3 of the saccharide residue may be converted to the keto form.
- ORC is available with a variety of degrees of oxidation and hence rates of degradation.
- the ORC may include particles, fibers, or both; in any embodiment disclosed herein, the ORC may be in the form of particles, such as fiber particles or powder particles.
- the ORC fibers may have a volume fraction such that at least 80% of the fibers have lengths in the range from about 5 pm to about 1000 pm, or from about 250 pm to about 450 pm.
- the outer layer and/or the inner core of any embodiment herein may include about 30 wt.% to about 70 wt.% ORC (for the outer layer, this may be crosslinked ORC) with a weight-average molecular weight of about 50,000 to about 1,000,000.
- the ORC of any embodiment disclosed herein may be included in an amount of about 30 wt.%, about 32 wt.%, about 34 wt.%, about 36 wt.%, about 38 wt.%, about 40 wt.%, about 42 wt.%, about 44 wt.%, about 46 wt.%, about 48 wt.%, about 50 wt.%, about 52 wt.%, about 54 wt.%, about 56 wt.%, about 58 wt.%, about 60 wt.%, about 62 wt.%, about 64 wt.%, about 66 wt.%, about 68 wt.%, about 70 wt.%, or any range including and/or in between any two of these values.
- the ORC may have a weight-average molecular weight of about 50,000, about 100,000, about 150,000, about 200,000, about 250,000, about 300,000, about 350,000, about 400,000, about 450,000, about 500,000, about 550,000, about 600,000, about 650,000, about 700,000, about 750,000, about 800,000, about 850,000, about 900,000, about 950,000, about 1,000,000, or any range including and/or in between any two of these values.
- a weight ratio of the one or more of collagen and chitosan to ORC may be about 60:40 to about 40:60 in the outer layer and/or the inner core.
- the weight ratio of the one or more of collagen and chitosan to ORC may be about 60:40, about 59:41, about 58:42, about 57:43, about 56:44, about 55:45, about 54:46, about 53:47, about 52:48, about 51 :49, about 50:50, about 49:51, about 48:52, about 47:53, about 46:54, about 45:55, about 44:56, about 43:57, about 42:58, about 41 :59, about 40:60, or any range including and/or in between any two of these values.
- the outer layer and/or the inner core may include about 0.001 wt.% to about 5 wt.% of an antimicrobial agent.
- the total amount of antimicrobial agent(s) in the outer layer and/or the inner core may independently for each be about 0.001 wt.%, about 0.002 wt.%, about 0.003 wt.%, about 0.004 wt.%, about 0.005 wt.%, about 0.006 wt.%, about 0.007 wt.%, about 0.008 wt.%, about 0.009 wt.%, about 0.01 wt.%, about 0.02 wt.%, about 0.03 wt.%, about 0.04 wt.%, about 0.05 wt.%, about 0.06 wt.%, about 0.07 wt.%, about 0.08 wt.%, about 0.09 wt.%, about 0.1 wt.%, about
- the antimicrobial agent may include a penicillin, a streptomycin, ionic silver (or a source for ionic silver), chlorhexidine, a poly(hexamethylene biguanide) (PHMB), iodine, or a combination of any two or more thereof.
- Suitable sources of ionic silver may include ionic silver in a variety of forms including as pharmaceutically acceptable salts, where representative examples include but are not limited to silver oxide, silver chromate, silver allantoinate, silver borate, silver glycerolate, silver nitrate, silver acetate, silver chloride, silver sulfate, silver lactate, silver bromide, silver iodide, silver carbonate, silver citrate, silver laurate, silver deoxycholate, silver salicylate, silver / -ami nobenzoate, silver -aminosalicylate, or a combination of any two or more thereof.
- ionic silver (or a source thereof) may initially be incorporated into the outer layer and/or inner core as a silver salt, at least a portion (if not substantially all) of the ionic silver may be complexed to, e.g ., ORC, in the outer layer and/or the inner core.
- the outer layer and inner core may contain varying concentration of any of the above referenced materials (e.g, biopolymers, plasticizers, antimicrobial agents, and/or additional materials as described herein in any embodiment).
- the outer layer may include about 50 wt.% to about 100 wt.% gelatin and the inner core may include intact collagen, such that the inner core has a higher concentration of collagen than the outer layer.
- both the outer layer and inner core may include one or more antimicrobial agents as described herein, where the outer layer may include a higher concentration of antimicrobial agents than the inner core.
- both the outer layer and inner core may include one or more
- the outer layer may include a lower concentration of antimicrobial agents than the inner core.
- the present disclosure provides a wound insert that includes an outer layer and an inner core.
- the outer layer may include a outward-facing side and an inner-core facing side.
- an exterior surface of the inner core may be adjoined with the inner core-facing side of the outer layer.
- the wound insert of the present technology may be in the shape of a cylinder, a sphere, a cube, a cuboid, a hexagonal prism, a cone, a square-based pyramid, triangular-based pyramid, or a triangular prism.
- the wound insert of the present technology may be in the shape of a cylinder, a cylinder with at least one rounded edge, cuboid, or a cuboid with at least one rounded edge.
- the wound insert may be in the shape of a cylinder, wherein the cylindrical wound insert further comprises a hemispherical compartment on each end of the wound insert (see FIGs. 1 A-1B).
- the wound insert may be in the shape of a cuboid with one or more rounded edges, wherein the cuboid wound insert further comprises a cubed compartment on each end of the wound insert (see FIGs. 2A-2B).
- the length of the wound insert of the present technology compared to the width may be from about 15: 1 to about 15:6.
- the length to width ratio may be about 15: 1, about 15:2, about 15:3, about 15:4, about 15:5, about 15:6, or any range including and/or in between any two of the preceding values.
- the width to height ratio of the wound insert according to the present technology may be about 3:2 to 2:3.
- the width to height ratio may be about 3 :2, about 3: 1, about 2: 1, about 1 : 1, about 1 :2, about 1 :3, about 2:3, or any range including and/or in between any two of the preceding values.
- the length of the wound insert of the present technology may be about 1 cm to about 10 cm.
- the length of the wound insert may be about 1 cm, about 1.1 cm, about 1.2 cm, about 1.3 cm, about 1.4 cm, about 1.5 cm, about 1.6 cm, about 1.7 cm, about 1.8 cm, about 1.9 cm, about 2.0 cm, about 2.2 cm, about 2.4 cm, about 2.6 cm, about 2.8 cm, about 3.0 cm, about 3.2 cm, about 3.4 cm, about 3.6 cm, about 3.8 cm, about 4.0 cm, about 4.2 cm, about 4.4 cm, about 4.6 cm, about 4.8 cm, about 5.0 cm, about 5.5 cm, about 6.0 cm, about 6.5 cm, about 7.0 cm, about 7.5 cm, about 8.0 cm, about 8.5 cm, about 9.0 cm, about 9.5 cm, about 10.0 cm, or any range including and/or in between any two of these values.
- the width and/or height of the wound insert of the present technology may be about 0.1 cm to about 3 cm.
- the width and/or height of the wound insert may be about 0.1 cm, about 0.2 cm, about 0.3 cm, about 0.4 cm, about 0.5 cm, about 0.6 cm, about 0.7 cm, about 0.8 cm, about 0.9 cm, about 1.0 cm, about 1.1 cm, about 1.2 cm, about 1.3 cm, about 1.4 cm, about 1.5 cm, about 1.6 cm, about 1.7 cm, about 1.8 cm, about 1.9 cm, about 2.0 cm, about 2.1 cm, about 2.2 cm, about 2.3 cm, about 2.4 cm, about 2.5 cm, about 2.6 cm, about 2.7 cm, about 2.8 cm, about 2.9 cm, about 3.0 cm, or any range including and/or in between any two of these values.
- the wound insert of the present technology may comprise perforations to facilitate tissue integration.
- the perforations of the wound insert may be about 0.1 mM to about 100 mM in width and/or height.
- the perforations of the wound insert may be about 0.1 pM to about 100 pM deep.
- the perforations of the wound insert may be through the entire thickness of the outer layer.
- FIG. 3 provides an illustrative side view illustration of a wound insert 300 that includes an outer layer 301, an inner core 302, and a plurality of perforations 303.
- the wound insert of the present technology may comprise through-holes through the entire width, height, and/or length of the wound insert, such as for beneficial use of the wound insert in negative pressure therapy.
- the through-holes of the wound insert may be about 2 mm to about 8 mm in width and/or height.
- the through-holes of the wound insert may be about 2 mm, about 2.2 mm, about 2.4 mm, about 2.6 mm, about 2.8 mm, about 3 mm, about 3.2 mm, about 3.4 mm, about 3.6 mm, about 3.8 mm, about 4 mm, about 4.2 mm, about 4.4 mm, about 4.6 mm, about 4.8 mm, about 5 mm, about 5.5 mm, about 6 mm, about 6.5 mm, about 7 mm, about 7.5 mm, about 8 mm, or any range including and/or in between any two of these values.
- FIG. 4 provides an illustrative side view illustration of a wound insert 400 that includes an outer layer 401, inner core 402, and a plurality of through-holes 403.
- the wound insert of the present disclosure may be sterile and packaged in a microorganism-impermeable container.
- the wound insert of any embodiment described herein may be employed in therapy in which a wound is treated with reduced pressure.
- Treatment of a wound with reduced pressure may be commonly referred to as“negative-pressure therapy,” but is also known by other names, including“negative-pressure wound therapy,”“reduced-pressure therapy,” “vacuum therapy,”“vacuum-assisted closure,” and“topical negative-pressure,” for example.
- Negative-pressure therapy may provide a number of benefits, including migration of epithelial and subcutaneous tissues, improved blood flow, and/or micro-deformation of tissue at a wound site. Together, these benefits may increase development of granulation tissue and reduce healing times.
- the system may be configured to provide negative-pressure to a wound in accordance with this specification.
- the system may generally include a negative-pressure supply, and may include or be configured to be coupled to a distribution component.
- a distribution component may refer to any combination
- complementary or ancillary component configured to be fluidly coupled to a negative- pressure supply in a fluid path between a negative-pressure supply and a wound.
- the wound insert may be configured to distribute negative pressure. Additionally or alternatively, the fluid path(s) may be reversed or a secondary fluid path may be provided to facilitate movement of fluid across a wound.
- the fluid pathways of the through-holes may be interconnected to improve distribution or collection of fluids.
- the fluid mechanics associated with using a negative-pressure source to reduce pressure in another component or location, such as within a sealed therapeutic environment, can be mathematically complex.
- the basic principles of fluid mechanics applicable to negative-pressure therapy are generally well-known to those skilled in the art.
- the process of reducing pressure may be described generally and illustratively herein as“delivering,” “distributing,” or“generating” negative pressure, for example.
- a fluid such as wound fluid (for example, wound exudates and other fluids) flows toward lower pressure along a fluid path.
- wound fluid for example, wound exudates and other fluids
- the term“downstream” typically implies something in a fluid path relatively closer to a source of negative pressure or further away from a source of positive pressure.
- the term“upstream” implies something relatively further away from a source of negative pressure or closer to a source of positive pressure.
- This orientation is generally presumed for purposes of describing various features and components herein.
- the fluid path may also be reversed in some applications (such as by substituting a positive-pressure source for a negative-pressure source) and this descriptive convention should not be construed as a limiting convention.
- Negative pressure may generally refer to a pressure less than a local ambient pressure, such as the ambient pressure in a local environment external to a sealed therapeutic environment provided by the wound insert.
- the local ambient pressure may also be the atmospheric pressure proximate to or about a wound.
- the pressure may be less than a hydrostatic pressure associated with the tissue at the wound. While the amount and nature of negative pressure applied to a wound may vary according to therapeutic requirements, the pressure is generally a low vacuum, also commonly referred to as a rough vacuum, between -5 mm Hg (-667 Pa) and -500 mm Hg (- 66.7 kPa), gauge pressure. Common therapeutic ranges are between -50 mm Hg (-6.7 kPa) and -300 mm Hg (-39.9 kPa), gauge pressure.
- a negative-pressure supply may be a reservoir of air at a negative pressure, or may be a manual or electrically-powered device that can reduce the pressure in a sealed volume, such as a vacuum pump, a suction pump, a wall suction port available at many healthcare facilities, or a micro-pump, for example.
- a negative-pressure supply may be housed within or used in conjunction with other components, such as sensors, processing units, alarm indicators, memory, databases, software, display devices, or user interfaces that further facilitate therapy.
- a negative- pressure source may be combined with a controller and other components into a therapy unit.
- a negative-pressure supply may also have one or more supply ports configured to facilitate coupling and de-coupling of the negative-pressure supply to one or more distribution components.
- components may be fluidly coupled to each other to provide a path for transferring fluids (i.e., liquid and/or gas) between the components.
- components may be fluidly coupled through a fluid conductor, such as a tube.
- a fluid conductor such as a tube.
- the term“fluid conductor” may include a tube, pipe, hose, conduit, or other structure with one or more lumina or open passages adapted to convey a fluid between two ends thereof.
- a fluid conductor may be an elongated, cylindrical structure with some flexibility, but the geometry and rigidity may vary.
- the negative-pressure source may be operatively coupled to the wound insert via an interface.
- a wound insert of any embodiment disclosed herein to the wound.
- the wound may be a tunneling wound, a dermal wound, a diabetic wound, an acute wound, a chronic wound, or a combination of any two or more thereof.
- Exemplary chronic wounds include, but are not limited to, infectious wounds, venous ulcers, decubitus ulcers, or diabetic ulcers.
- the wound is a tunneling wound.
- the method may include administering two or more wound inserts to the wound.
- the wound insert may be administered directly to the wound. Any method known to those in the art for administering a wound insert to a tunneling wound, a dermal wound, a diabetic wound, an acute wound, or a chronic wound disclosed herein may be employed. Suitable methods include in vitro or in vivo methods. In vivo methods typically include the administration of one or more wound inserts to a subject in need thereof, suitably a human. When used in vivo for therapy, the one or more wound inserts described herein are administered to the subject in effective amounts (i.e., amounts that have desired therapeutic effect). The dose and dosage regimen will depend upon the state of the wound of the subject and the characteristics of the particular wound insert used.
- the effective amount may be determined during pre-clinical trials and clinical trials by methods familiar to physicians and clinicians.
- An effective amount of one or more wound inserts useful in the methods may be administered to a subject in need thereof by any number of well-known methods for administering wound inserts.
- the wound inserts may be administered daily for 1 hour or more, for 2 hours or more, for 3 hours or more, for 4 hours or more, for 5 hours or more, for 6 hours or more, or for 12 hours or more.
- the wound inserts may be administered one, two, three, four, or five times per day.
- the wound inserts may be administered daily for one, two, three, four, or five weeks.
- the wound inserts may be administered daily for less than 6 weeks.
- the wound inserts may be administered daily for 6 weeks or more.
- the wound inserts may be administered daily for 12 weeks or more.
- the wound inserts may be administered every day, every other day, every third day, every fourth day, every fifth day, or every sixth day. In any embodiment disclosed herein, the wound inserts may be administered weekly, bi-weekly, tri-weekly, or monthly. In any embodiment disclosed herein, the wound inserts may be administered for a chronic wound as appropriate.
- the method may include employing the wound insert in the context of a negative-pressure therapy, where the negative-pressure therapy may include positioning the wound insert in and/or proximate to the wound.
- the negative-pressure therapy may further include sealing the wound insert to tissue surrounding the wound to form a sealed space.
- the wound insert may be positioned in and/or proximate to the wound and sealed to an attachment surface near the wound, for example, to undamaged epidermis peripheral to a wound.
- the negative-pressure therapy method in any embodiment herein may further include fluidly coupling a negative-pressure source to the sealed space and operating the negative-pressure source to generate a negative pressure in the sealed space.
- the negative-pressure source may be coupled to the wound insert such that the negative- pressure source may be used to reduce the pressure in the sealed space.
- negative pressure applied across the wound, for example, via the wound insert may be effective to induce macrostrain and microstrain at the wound site, as well as remove exudates and other fluids from the wound.
- a method of manufacturing a wound insert of any embodiment of the present technology includes: fabricating an outer layer of the wound insert from a first slurry comprising one or more biopolymers, wherein the outer layer is in a shape having a hollow center; photo-crosslinking and/or reagent-crosslinking the outer layer to obtain one or more photocrosslinked and/or reagent- crosslinked biopolymers; drying the outer layer of the wound insert; depositing a second slurry into the hollow center of the outer layer to form an inner core of the wound insert; and removing residual moisture from the inner core, where the shape of the outer layer may be a cylinder, a sphere, a cube, a cuboid, a hexagonal prism, a cone, a square-based pyramid, triangular-based pyramid, or a triangular prism; the second slurry includes a biopolymer; the outer layer exhibits a modulus of elasticity from about
- the fabricating may include extrusion of the first slurry to fabricate the outer layer.
- the first slurry may be extruded via a die having a hollow center to obtain a shape (e.g ., a tube structure).
- the outer layer shape i.e., tube structure
- the outer layer shape may be a cylinder, a sphere, a cube, a cuboid, a hexagonal prism, a cone, a square-based pyramid, triangular-based pyramid, or a triangular prism.
- the first slurry may have a pH from about 3 to 7.
- the first slurry may have a pH of about 3, about 3.5, about 4, about 4.5, about 5, about 5.5, about 6, about 6.5, about 7, or any range including and/or in between any two or more of the preceding values.
- the pH of the first slurry may be from about 4.5 to about 5.5.
- the first slurry may further include at least one plasticizer as described herein in any embodiment.
- the at least one plasticizer may be included in the amount of about 2 wt.% to about 30 wt.% within the first slurry.
- the at least one plasticizer may be included in the amount of about 2 wt.%, about 3 wt.%, about 4 wt.%, about 5 wt.%, about 6 wt.%, about 7 wt.%, about 8 wt.%, about 9 wt.%, about 10 wt.%, about 11 wt.%, about 12 wt.%, about 13 wt.%, about 14 wt.%, about 15 wt.%, about 16 wt.%, about 17 wt.%, about 18 wt.%, about 19 wt.%, about 20 wt.%, about 21 wt.%, about 22 wt.%, about 23 wt.%, about 24 wt.%, about 25 wt.%, about 26 wt.%, about 27 wt.%, about 28 wt.%, about 29 wt.%, about 30 wt.%, or any range including and/or in
- the first slurry and/or second slurry correspond to the resultant outer layer and/or inner core, respectively.
- the first slurry and/or second slurry may include one or more biopolymers including, but not limited to, a collagen, an oxidized cellulose, an oxidized regenerated cellulose (ORC), a
- the collagen of the first slurry and/or the second slurry may include a mammalian collagen, such as a bovine collagen, a human collagen, or a combination thereof as described herein in any embodiment.
- the amount of collagen included in the first slurry and/or the second slurry of any embodiment herein may be about 30 wt.% to 100 wt.% as described herein in any
- the amount of collagen may be about 30 wt.%, about 32 wt.%, about 34 wt.%, about 36 wt.%, about 38 wt.%, about 40 wt.%, about 42 wt.%, about 44 wt.%, about 46 wt.%, about 48 wt.%, about 50 wt.%, about 52 wt.%, about 54 wt.%, about 56 wt.%, about 58 wt.%, about 60 wt.%, about 62 wt.%, about 64 wt.%, about 66 wt.%, about 68 wt.%, about 70 wt.%, about 72 wt.%, about 74 wt.%, about 76 wt.%, about 78 wt.%, about 80 wt.%, about 82 wt.%, about 84 wt.%, about 86 wt.%, about 88
- the collagen included in the first slurry and/or second slurry of any embodiment herein may have a weight-average molecular weight of about 5,000, about 6,000, about 7,000, about 8,000, about 9,000, about 10,000, about 12,000, about 14,000, about 16,000, about 18,000, about 20,000, about 22,000, about 24,000, about 26,000, about 28,000, about 30,000, about 32,000, about 34,000, about 36,000, about 38,000, about 40,000, about 45,000, about 50,000, about 55,000, about 60,000, about 65,000, about 70,000, about 75,000, about 80,000, about 85,000, about 90,000, about 95,000, about 100,000, or any range including and/or in between any two of these values.
- the first slurry and/or second slurry may include ORC as described herein in any embodiment.
- the first slurry and/or the second slurry of any embodiment herein may include about 30 wt.% to about 70 wt.% ORC (for the outer layer, this may be crosslinked ORC) with a weight-average molecular weight of about 50,000 to about 1,000,000.
- the ORC of any embodiment disclosed herein may be included in an amount of about 30 wt.%, about 32 wt.%, about 34 wt.%, about 36 wt.%, about 38 wt.%, about 40 wt.%, about 42 wt.%, about 44 wt.%, about 46 wt.%, about 48 wt.%, about 50 wt.%, about 52 wt.%, about 54 wt.%, about 56 wt.%, about 58 wt.%, about 60 wt.%, about 62 wt.%, about 64 wt.%, about 66 wt.%, about 68 wt.%, about 70 wt.%, or any range including and/or in between any two of these values.
- the ORC may have a weight-average molecular weight of about 50,000, about 100,000, about 150,000, about 200,000, about 250,000, about
- a weight ratio of the one or more of collagen and chitosan to ORC may be about 60:40 to about 40:60 in the first slurry and/or the second slurry.
- the weight ratio of the one or more of collagen and chitosan to ORC may be about 60:40, about 59:41, about 58:42, about 57:43, about 56:44, about 55:45, about 54:46, about 53 :47, about 52:48, about 51 :49, about 50:50, about 49:51, about 48:52, about 47:53, about 46:54, about 45:55, about 44:56, about 43 :57, about 42:58, about 41 :59, about 40:60, or any range including and/or in between any two of these values.
- the first slurry and/or second slurry may include about 0.001 wt.% to about 5 wt.% of an antimicrobial agent as described herein in any embodiment.
- the total amount of antimicrobial agent(s) in the outer layer and/or the inner core may independently for each be about 0.001 wt.%, about 0.002 wt.%, about 0.003 wt.%, about 0.004 wt.%, about 0.005 wt.%, about 0.006 wt.%, about 0.007 wt.%, about 0.008 wt.%, about 0.009 wt.%, about 0.01 wt.%, about 0.02 wt.%, about 0.03 wt.%, about 0.04 wt.%, about 0.05 wt.%, about 0.06 wt.%, about 0.07 wt.%, about 0.08 wt.%, about 0.09 wt.%,
- the method may further include treating the outer layer with a weak basic gas.
- the weak gas may be ammonia.
- the method includes photocrosslinking and/or reagent crosslinking the outer layer to obtain one or more crosslinked biopolymers.
- crosslinking may be carried out by exposing the outer layer to light with a wavelength from about 360 nm to about 370 nm.
- the total radiant power of all wavelengths of light used to crosslink the one or more biopolymers of the outer layer may be from about 10 mW/cm 2 to about 1000 mW/cm 2 .
- the total radiant power of all wavelengths of light used to crosslink the biopolymer of the outer layer may be from about 10 mW/cm 2 , about 15 mW/cm 2 , about 20 mW/cm 2 , about 25 mW/cm 2 , about 30 mW/cm 2 , about 35 mW/cm 2 , about 40 mW/cm 2 , about 45 mW/cm 2 , about 50 mW/cm 2 , about 55 mW/cm 2 , about 60 mW/cm 2 , about 65 mW/cm 2 , about 70 mW/cm 2 , about 75 mW/cm 2 , about 80 mW/cm 2 , about 85 mW/cm 2 , about 90 mW/cm 2 , about 95 mW/cm 2 , about 100 mW/cm 2 , about 110 mW/cm 2 , about 120 mW/cm
- Reagent-crosslinking may be carried out by cross-linking compounds, where part of the cross-linking compound is incorporated into the biopolymer to generate reagent- crosslinked biopolymers as described herein.
- exemplary reagent-crosslinked biopolymers are biopolymers crosslinked by one or more of disuccinimidyl suberate (DSS),
- disuccinimidyl tartrate DST
- dithiobis succinimidyl propionate DSP
- bismaleimidoethane BMOE
- dithiobismaleimidoethane DTME
- MBS bismaleimidoethane
- DTME dithiobismaleimidoethane
- GMBS L-g-mal eimi dobutyryl -oxy sued ni mi de ester
- EMCS N-e- maleimidocaproyloxy-succinimide ester
- sulfo-EMCS L-e-maleimidocaproyl- oxysulfosuccinimide ester
- exemplary reagent-crosslinked biopolymers are biopolymers crosslinked in the presence of light (e.g ., 250-350 nm light) with N-((2- pyridyldithio)ethyl)-4-azidosalicylamide and/or A f -5-azi do-2-nitrobenzyl oxy succi ni mi de - thus, light may be used to initiate the crosslinking reaction of the cross-linking compound with a biopolymer.
- light e.g ., 250-350 nm light
- the drying may be carried out at a temperature from about 20 °C to about 80 °C. Suitable drying temperatures in any embodiment herein may include, but are not limited to, about 20 °C, about 25 °C, about 30 °C, about 35 °C, about 40 °C, about 45 °C, about 50 °C, about 55 °C, about 60 °C, about 65 °C, about 70 °C, about 75 °C, about 80 °C , or any range including and/or in between any two of the preceding values. The drying may be carried out for a duration of about 2 hours to about 24 hours.
- the drying may be carried out for about 2 hours, about 3 hours, about 4 hour, about 5 hours, about 6 hours, about 7 hours, about 8 hours, about 9 hours, about 10 hours, about 11 hours, about 12 hours, about 13 hours, about 14 hours, about 15 hours, about 16 hours, about 17 hours, about 18 hours, about 19 hours, about 20 hours, about 21 hours, about 22 hours, about 23 hours, about 24 hours, or any range including and/or in between any two of the preceding values.
- depositing the second slurry may include injecting or extruding the second slurry within the outer layer’s hollow center to form the inner core.
- the method includes removing residual water from the inner core.
- removing the residual moisture from the inner core may include freeze-drying the inner core.
- the inner core may retain 0% to about 5% of residual moisture. Suitable amounts of residual moisture may include, but are not limited to, about 0.05%, about 0.1%, about 0.5%, about 1%, about 2%, about 3%, about 4%, about 5%, or any range including and/or in between any two of the preceding values.
- the method may include shaping (e.g ., hemispherical, cubed, or other suitable shape) excess outer layer to form a fully or partially closed end of the wound insert (see FIGS. 1 A and 2A).
- shaping e.g ., hemispherical, cubed, or other suitable shape
- the present disclosure provides a wound insert prepared according to the method of manufacturing said wound insert as described herein in any embodiment.
- kits that include a wound insert of any embodiment disclosed herein and instructions for use.
- the kits of the present technology may also include methods for treating a wound in a subject in need thereof.
- the kit may optionally comprise components such as antiseptic wipes, ointment, adhesive tape, tweezers, scissors, etc.
Abstract
The present disclosure relates generally to wound inserts that may include an outer layer and an inner core of biopolymers that may be used in the therapy of tunneling wounds and for facilitating wound healing. Methods of use, methods for manufacture, and kits for use in practicing the methods are also provided.
Description
WOUND INSERTS FOR TREATMENT OF TUNNELING WOUNDS
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims the benefit of and priority to U.S. Patent Application No. 62/868,629, filed on June 28, 2019, the contents of which are incorporated herein in their entirety.
TECHNICAL FIELD
[0002] The present technology relates generally to wound inserts and methods for facilitating wound healing. Methods of use, methods for manufacture, and kits for use in practicing the methods are also provided.
BACKGROUND
[0003] The following description of the background of the present technology is provided simply as an aid in understanding the present technology and is not admitted to describe or constitute prior art to the present technology.
[0004] A wide variety of materials and devices, generally characterized as“dressings,” are generally known in the art for use in treating an injury or other disruption of tissue. Such wounds may be the result of trauma, surgery, or disease, and may affect skin or other tissues. In general, dressings may control bleeding, absorb wound exudate, ease pain, assist in debriding the wound, protect wound tissue from infection, or otherwise promote healing and protect the wound from further damage.
[0005] Healing wounds with complex configurations, such as lengthy tunneling wounds, can be very challenging since some of such wounds do not respond to mainstream wound care treatment. Wounds that do not respond to treatment can not only lead to a chronic wound, but also patient mortality.
SUMMARY
[0006] In an aspect, a wound insert is provided that includes an outer layer and an inner core. The outer layer includes a photocrosslinked biopolymer, a reagent-crosslinked biopolymer, or both (collectively,“crosslinked biopolymer”), and the inner core includes a
biopolymer. Further, the outer layer exhibits a modulus of elasticity from about 0.5 MPa to about 5.0 MPa; and the inner core exhibits a lower modulus of elasticity.
[0007] In a related aspect, a method for treating a wound in a subject is provided, where the method includes administering a wound insert of any embodiment disclosed herein to the wound.
[0008] In a further related aspect, a kit is provided that includes a wound insert of any embodiment disclosed herein as well as instructions for use.
[0009] In a further related aspect, a method of manufacturing a wound insert of any embodiment of the present technology is provided. The method includes fabricating an outer layer of the wound insert from a first slurry comprising one or more biopolymers, wherein the outer layer is in a shape having a hollow center; photo-crosslinking and/or reagent crosslinking the outer layer to obtain one or more photocrosslinked and/or reagent- crosslinked biopolymers; drying the outer layer of the wound insert; depositing a second slurry into the hollow center of the outer layer to form an inner core of the wound insert; and removing residual moisture from the inner core, where the shape of the outer layer may be a cylinder, a sphere, a cube, a cuboid, a hexagonal prism, a cone, a square-based pyramid, triangular-based pyramid, or a triangular prism; the second slurry includes a biopolymer; the outer layer exhibits a modulus of elasticity from about 0.5 MPa to about 5.0 MPa; and the inner core exhibits a lower modulus of elasticity than the outer layer.
BRIEF DESCRIPTION OF THE DRAWINGS
[0010] FIGs. 1 A-1B show cross-sectional views of a diagrammatic representation of an embodiment of an insert of the present technology having a cylindrical shape.
[0011] FIGs. 2A-2B show cross-sectional views of a diagrammatic representation of an embodiment of an insert of the present technology having a cuboidal shape with rounded edges.
[0012] FIG. 3 shows a cross-sectional view of a diagrammatic representation of an embodiment of an insert of the present technology having a cuboidal shape with rounded edges and perforations in the outer layer.
[0013] FIG. 4 shows a cross-sectional view of a diagrammatic representation of an embodiment of an insert of the present technology having a cuboidal shape with rounded edges and though-holes.
[0014] It should be noted that the representative illustrations provided in the figures set forth herein is intended to illustrate the general features and/or characteristics of exemplary embodiments to aid in describing the present technology in full. The figures may not precisely reflect the characteristics of any given embodiment, and are not necessarily intended to define or limit the scope of the claimed subject matter. Further, the present technology may or may not include or incorporate therewith any one or more features of characteristics set provided in any one or more figures.
DETAILED DESCRIPTION
[0015] It is to be appreciated that certain aspects, modes, embodiments, variations, and features of the present methods are described below in various levels of detail in order to provide a substantial understanding of the present technology.
Definitions
[0016] The definitions of certain terms as used in this specification are provided below. Unless defined otherwise, all technical and scientific terms used herein generally have the same meaning as commonly understood by one of ordinary skill in the art to which this present technology belongs.
[0017] The following terms are used throughout as defined below.
[0018] As used herein and in the appended claims, singular articles such as“a”,“an”, and “the” and similar referents in the context of describing the elements (especially in the context of the following claims) are to be construed to cover both the singular and the plural, unless otherwise indicated herein or clearly contradicted by context. Recitation of ranges of values herein are merely intended to serve as a shorthand method of referring individually to each separate value falling within the range, unless otherwise indicated herein, and each separate value is incorporated into the specification as if it were individually recited herein. All methods described herein can be performed in any suitable order unless otherwise indicated herein or otherwise clearly contradicted by context. The use of any and all examples, or
exemplary language ( e.g .,“such as”) provided herein, is intended merely to better illuminate the embodiments and does not pose a limitation on the scope of the claims unless otherwise stated. No language in the specification should be construed as indicating any non-claimed element as essential.
[0019] As used herein,“about” will be understood by persons of ordinary skill in the art and will vary to some extent depending upon the context in which it is used. If there are uses of the term which are not clear to persons of ordinary skill in the art, given the context in which it is used,“about” will mean up to plus or minus 10% of the particular term - for example,“about 10 wt.%” would mean“9 wt.% to 11 wt.%.” It is to be understood that when“about” precedes a term, the term is to be construed as disclosing“about” the term as well as the term without modification by“about” - for example,“about 10 wt.%” discloses “9 wt.% to 11 wt.%” as well as discloses“10 wt.%.”
[0020] As used herein, the term“modulus of elasticity” (also known as“Young’s modulus”) refers to the measure of an object or a substance’s resistance to being deformed elastically (i.e., non-permanently) upon the application of a stress. The modulus of elasticity of an object is defined by the following formula:
wherein“stress” is the force causing the deformation divided by the area to which the force is applied, and wherein“strain” is the ratio of the change in some parameter caused by the deformation to the original value of the parameter.
[0021] As used herein, the term“radiant power” or“irradiance” refers to the radiant flux or power received by a surface (e.g., a biopolymer of an outer layer of a wound insert as disclosed herein) per unit area. The SI unit of irradiance is the watt per square meter (W/m2).
[0022] As used herein, the“administration” of a wound insert to a subject includes any route of introducing or delivering to a subject a wound insert to perform its intended function. Administration can be carried out by any suitable route, including, but not limited to, topical administration. Administration includes self-administration and the administration by another.
[0023] As used herein, the term“effective amount” refers to a quantity sufficient to achieve a desired therapeutic and/or prophylactic effect, e.g, an amount which results in the decrease
in a wound described herein or one or more signs or symptoms associated with a wound described herein. In the context of therapeutic and/or prophylactic applications, the amount of an insert administered to the subject will vary depending on the composition, the degree, type, and severity of the wound and on the characteristics of the individual. The inserts can also be administered in combination with one or more additional therapeutic compounds. In the methods described herein, the therapeutic inserts may be administered to a subject having one or more wounds.
[0024] As used herein, the terms“individual”,“patient”, or“subject” can refer to an individual organism, a vertebrate, a mammal, or a human. In some embodiments, the individual, patient, or subject is a human.
[0025] “Treating” or“treatment” as used herein covers the treatment of a wound described herein, in a subject, such as a human, and includes: (i) inhibiting a wound, i.e., arresting its development; (ii) relieving a wound, i.e., causing regression of the wound; (iii) slowing progression of the wound; and/or (iv) inhibiting, relieving, or slowing progression of one or more symptoms of the wound. In some embodiments, treatment means that the symptoms associated with the wound are alleviated, reduced, cured, or placed in a state of remission.
[0026] It is also to be appreciated that the various modes of treatment of wounds as described herein are intended to mean“substantial,” which includes total but also less than total treatment, and wherein some biologically or medically relevant result is achieved. The treatment may be a continuous prolonged treatment for a chronic wound or a single administration, or a few administrations for the treatment of an acute wound.
The Present Technology
[0027] A lengthy tunneling wound can be very challenging to heal since such wounds do not respond to mainstream wound care treatment. Such wounds can not only lead to chronic wound formation, but also patient mortality.
[0028] The present disclosure is directed to wound inserts that include an outer layer and an inner core of biologically-active biopolymers. The wound inserts of the present technology advantageously may exhibit reduced wound packing pressure on the sides of the wound tunnel and may decrease bioburden due to antimicrobial properties of the wound insert. The wound insert of the present technology may further help prevent the collapse of the wound.
The components of the wound insert may stimulate tissue growth and/or prevent bacterial infection. The components of the wound insert may reduce the inflammatory phase, may stimulate granulation tissue growth, and/or may reduce bacterial bioburden. The wound insert of the present technology may further be configured, due to the nature of the outer layer, with a bioresorbable suture thread to facilitate removal of the wound insert for wound assessment.
[0029] Thus, in an aspect, a wound insert is provided that includes an outer layer and an inner core. The outer layer includes a crosslinked biopolymer, such as a photocrosslinked biopolymer, a reagent-crosslinked biopolymer, or both, and the inner core includes a biopolymer. Further, in any embodiment herein, the outer layer exhibits a modulus of elasticity from about 0.5 MPa to about 5.0 MPa; and the inner core exhibits a lower modulus of elasticity. Therefore, the outer layer of any embodiment disclosed herein may exhibit a modulus of elasticity of about 0.5 MPa, about 0.6 MPa, about 0.7 MPa, about 0.8 MPa, about 0.9 MPa, about 1.0 MPa, about 1.3 MPa, about 1.4 MPa, about 1.5 MPa, about 1.6 MPa, about 1.7 MPa, about 1.8 MPa, about 1.9 MPa, about 2.0 MPa, about 2.1 MPa, about 2.2 MPa, about 2.3 MPa, about 2.4 MPa, about 2.5 MPa, about 2.6 MPa, about 2.7 MPa, about 2.8 MPa, about 2.9 MPa, about 3.0 MPa, about 3.1 MPa, about 3.2 MPa, about 3.3 MPa, about 3.4 MPa, about 3.5 MPa, about 3.6 MPa, about 3.7 MPa, about 3.8 MPa, about 3.9 MPa, about 4.0 MPa, about 4.1 MPa, about 4.2 MPa, about 4.3 MPa, about 4.4 MPa, about 4.5 MPa, about 4.6 MPa, about 4.7 MPa, about 4.8 MPa, about 4.9 MPa, about 5.0 MPa, or any range including and/or in between any two of these values. As discussed above, the inner core exhibits a lower modulus of elasticity than the outer layer. In any embodiment disclosed herein, the inner core may exhibit a modulus of elasticity of about 0.0 MPa, about 0.1 MPa, about 0.2 MPa, about 0.3 MPa, about 0.5 MPa, or any range including and/or in between any two of these values.
[0030] FIGs. 1 A-1B and 2A-2B provide non-limiting representative illustrations of embodiments of a wound insert of the present technology, illustrating the outer layer (101 and 201, respectively) and of the inner core (102 and 202, respectively) of such a wound insert. FIG. 1 A provides an illustrative side view illustration of a wound insert 100 having a cylindrical shape that includes an outer layer 101 and an inner core 102. FIG. IB provides an illustrative cross-sectional view of the wound insert 100 having a cylindrical shape. FIG. 2 A provides an illustrative side view illustration of a wound insert 200 having a cuboidal shape
with rounded edges that includes an outer layer 201 and an inner core 202. FIG. 2B provides an illustrative cross-sectional view illustration of the wound insert 200 having a cuboidal shape with rounded edges.
The Outer Laver
[0031] In any embodiment disclosed herein, the outer layer may include an inner core facing side and a side facing away from the inner core (i.e., outer facing side). The outer facing side of the outer layer may be configured to be in contact with a wound when in use.
In any embodiment disclosed herein, it may be that the outer layer envelopes the inner core.
[0032] In any embodiment disclosed herein, the wound insert may further include a suture thread connected to and extending from the outer layer and advantageously allowing for the removal of the wound insert if, for example, such removal is desired to assess the healing progress of a wound. The suture thread may be a bioresorbable suture thread. Bioresorbable suture thread materials include, but are not limited to, a poly(glycolic acid), a poliglycaprone (a copolymer of glycolide and a caprolactone, such as a copolymer of glycolide and e- caprolactone), a polydioxanone, a collagen, or a combination of any two or more thereof. Further exemplary materials are poliglycaprone 25 and polyglactin 910. Suture threads of any embodiment herein may be monofilament or polyfilament suture threads, where polyfilament suture threads may be braided. The length of the suture thread as measured extending from the outer layer (i.e., not including the portion of suture thread connected to the outer layer) may be about 0.1 centimeters (cm) to about 10 cm.
[0033] The thickness of the outer layer of any embodiment herein may be about 20 mM to about 300 mM Thus, the thickness of the outer layer may be about 20 mM, about 22 mM, about 24 mM, about 26 mM, about 28 mM, about 30 mM, about 32 mM, about 34 mM, about 36 mM, about 38 mM, about 40 mM, about 42 mM, about 44 mM, about 46 mM, about 48 mM, about 50 mM, about 55 mM, about 60 mM, about 65 mM, about 70 mM, about 75 mM, about 80 mM, about 85 mM, about 90 mM, about 95 mM, about 100 mM, about 110 mM, about 120 mM, about 130 mM, about 140 mM, about 150 mM, about 160 mM, about 170 mM, about 180 mM, about 190 mM, about 200 mM, about 220 mM, about 240 mM, about 260 mM, about 280 mM, about 300 mM, or any range including and/or in between any two of these values.
[0034] The crosslinked biopolymer of the outer layer may include a collagen, an oxidized cellulose, an oxidized regenerated cellulose (ORC), a polysaccharide, chitosan, gelatin,
hyaluronic acid, or a combination of any two or more thereof. The outer layer may include about 0.01 wt.% to 100 wt.% of crosslinked biopolymer. Thus, the outer layer may include crosslinked biopolymer in an amount (based on the total weight of the outer layer) of about 0.01 wt.%, about 0.1 wt.%, about 1 wt.%, about 2 wt.%, about 3 wt.%, about 4 wt.%, about 5 wt.%, about 6 wt.%, about 7 wt.%, about 8 wt.%, about 9 wt.%, about 10 wt.%, about 12 wt.%, about 14 wt.%, about 16 wt.%, about 18 wt.%, about 20 wt.%, about 25 wt.%, about 30 wt.%, about 35 wt.%, about 40 wt.%, about 45 wt.%, about 50 wt.%, about 55 wt.%, about 60 wt.%, about 65 wt.%, about 70 wt.%, about 75 wt.%, about 80 wt.%, about 85 wt.%, about 90 wt.%, about 95 wt.%, 100 wt.%, or any range including and/or in between any two of these values. In any embodiment herein, the outer layer may include from about 50 wt.% to about 100 wt.% gelatin. In any embodiment herein, the outer layer may include collagen and ORC. In any embodiment herein, the outer layer may include collagen, ORC, and gelatin.
[0035] Photocrosslinked biopolymers are to be understood as biopolymers that have been crosslinked due to light and that do not include a cross-linking compound (cross-linking compounds are used to produce the reagent-crosslinked biopolymers, as discussed herein). The photocrosslinked biopolymer of the outer layer may be produced from a biopolymer that is photocrosslinked by exposure to light with a wavelength from about 360 nm to about 370 nm. The total radiant power of all wavelengths of light used to crosslink the biopolymer of the outer layer may be from about 10 mW/cm2 to about 1000 mW/cm2. Thus, the total radiant power of all wavelengths of light used to crosslink the biopolymer of the outer layer may be from about 10 mW/cm2, about 15 mW/cm2, about 20 mW/cm2, about 25 mW/cm2, about 30 mW/cm2, about 35 mW/cm2, about 40 mW/cm2, about 45 mW/cm2, about 50 mW/cm2, about 55 mW/cm2, about 60 mW/cm2, about 65 mW/cm2, about 70 mW/cm2, about 75 mW/cm2, about 80 mW/cm2, about 85 mW/cm2, about 90 mW/cm2, about 95 mW/cm2, about 100 mW/cm2, about 110 mW/cm2, about 120 mW/cm2, about 130 mW/cm2, about 140 mW/cm2, about 150 mW/cm2, about 160 mW/cm2, about 170 mW/cm2, about 180 mW/cm2, about 190 mW/cm2, about 200 mW/cm2, about 210 mW/cm2, about 220 mW/cm2, about 230 mW/cm2, about 240 mW/cm2, about 250 mW/cm2, about 260 mW/cm2, about 270 mW/cm2, about 280 mW/cm2, about 290 mW/cm2, about 300 mW/cm2, about 310 mW/cm2, about 320 mW/cm2, about 330 mW/cm2, about 340 mW/cm2, about 350 mW/cm2, about 360 mW/cm2, about 370 mW/cm2, about 380 mW/cm2, about 390 mW/cm2, about 400 mW/cm2, about 410 mW/cm2, about 420 mW/cm2, about 430 mW/cm2, about 440 mW/cm2, about 450 mW/cm2, about 460 mW/cm2, about 470 mW/cm2, about 480 mW/cm2, about 490 mW/cm2, about 500
mW/cm2, about 550 mW/cm2, about 600 mW/cm2, about 650 mW/cm2, about 750 mW/cm2, about 800 mW/cm2, about 850 mW/cm2, about 900 mW/cm2, about 950 mW/cm2, about 1000 mW/cm2, or any range including and/or in between any two of these values. The biopolymer of the outer layer may be photo-crosslinked with light for a period of about 1 minute to about 100 minutes.
[0036] Reagent-crosslinked biopolymer are biopolymers that are crosslinked via cross- linking compounds where part of the cross-linking compound is incorporated to generate the reagent-crosslinked biopolymer. Exemplary reagent-crosslinked biopolymers are
biopolymers crosslinked by one or more of disuccinimidyl suberate (DSS), disuccinimidyl tartrate (DST), dithiobis succinimidyl propionate (DSP), bismaleimidoethane (BMOE), dithiobismaleimidoethane (DTME), /??-m al ei mi dob enzoy 1 -A -hydroxy succi ni m i de ester (MBS), L-g-mal ei mi dobutyryl -oxy succi ni mi de ester (GMBS), A-e-m al ei m i docaproy 1 oxy- succinimide ester (EMCS), and /V-e-maleimidocaproyl-oxysulfosuccinimide ester (sulfo- EMCS). Other exemplary reagent-crosslinked biopolymers are biopolymers crosslinked in the presence of light ( e.g ., 250-350 nm light) with A-((2-pyridyldithio)ethyl)-4- azidosalicylamide and/or A-5-azido-2-nitrobenzyloxysuccinimide - thus, light may be used to initiate the crosslinking reaction of the cross-linking compound with a biopolymer.
[0037] In any embodiment disclosed herein, the outer layer may include at least one plasticizer. The at least one plasticizer may be included in the amount of about 2 wt.% to about 30 wt.% within the outer layer. Thus, the at least one plasticizer may be included in the amount of about 2 wt.%, about 3 wt.%, about 4 wt.%, about 5 wt.%, about 6 wt.%, about 7 wt.%, about 8 wt.%, about 9 wt.%, about 10 wt.%, about 11 wt.%, about 12 wt.%, about 13 wt.%, about 14 wt.%, about 15 wt.%, about 16 wt.%, about 17 wt.%, about 18 wt.%, about 19 wt.%, about 20 wt.%, about 21 wt.%, about 22 wt.%, about 23 wt.%, about 24 wt.%, about 25 wt.%, about 26 wt.%, about 27 wt.%, about 28 wt.%, about 29 wt.%, about 30 wt.%, or any range including and/or in between any two of these values. Exemplary plasticizers include, but are not limited to, an acetylated monoglyceride, an alkyl citrate, methyl ricinoleate, glycerol, or a combination of any two or more thereof. Examples of alkyl citrates include, but are not limited to, triethyl citrate, acetyl triethyl citrate, tributyl citrate, acetyl tributyl citrate, trioctyl citrate, acetyl trioctyl citrate, trihexyl citrate, acetyl trihexyl citrate, butyryl trihexyl citrate, trimethyl citrate, or a combination of any two or more thereof.
[0038] In any embodiment disclosed herein, the outer layer may include one or more additional materials. Suitable additional materials may include, but are not limited to, biocompatible dyes, non— steroidal anti-inflammatory drug ( e.g ., acetaminophen), hyaluronic acid, a steroid, an antibiotic (e.g., penicillins and/or streptomycins), glycoproteins (e.g, lipids), growth factors (e.g, fibroblast growth factor (FGF), an epidermal growth factor (RGF), a platelet derived growth factor (PGDF)), or a combination of any two or more thereof. In any embodiment herein, the biocompatible dye may include, but is not limited to, E124, fluorescein isothiocyanate (FITC), 4’,6-diamidino-2-phenylindole (DAPI), methylene blue, erythrosine B, ponceau S, alura red, SYBR green, alcian blue, brilliant blue G, calcein blue, cardio green, crystal violet, nile blue, india ink, brilliant blue, indigo carmine, Sudan III, methyl green, oil red, pyronin Y, tattoo ink, purpurin, phloxine B, picric acid, carbon nanotubes, a fuchsin, resazurin, a trichrome, or a combination of any two or more thereof.
The Inner Core
[0039] In any embodiment disclosed herein, the inner core may include a wound-facing side.
[0040] The biopolymer of the inner core may be a collagen, an oxidized cellulose, and oxidized regenerated cellulose (ORC), a polysaccharide, chitosan, gelatin, hyaluronic acid, or a combination of any two or more thereof. The inner core may include about 10 wt.% to about 100 wt.% of the biopolymer; thus, the inner core may include the biopolymer at an amount (based on the weight of the inner core) of about 10 wt.%, about 15 wt.%, about 20 wt.%, about 25 wt.%, about 30 wt.%, about 35 wt.%, about 40 wt.%, about 45 wt.%, about 50 wt.%, about 55 wt.%, about 60 wt.%, about 65 wt.%, about 70 wt.%, about 75 wt.%, about 80 wt.%, about 85 wt.%, about 90 wt.%, about 95 wt.%, about 99 wt.%, about 100 wt.%, or any range including and/or in between any two of these values. In any embodiment herein, the inner core may include less than about 0.01 wt.% of crosslinked biopolymer.
[0041] In any embodiment disclosed herein, the inner core may include one or more additional materials. Suitable additional materials may include, but are not limited to, biocompatible dyes, non— steroidal anti-inflammatory drug (e.g, acetaminophen), hyaluronic acid, a steroid, an antibiotic (e.g, penicillins and/or streptomycins), glycoproteins (e.g, lipids), growth factors (e.g, fibroblast growth factor (FGF), an epidermal growth factor (RGF), a platelet derived growth factor (PGDF)), or a combination of any two or more
thereof. In any embodiment herein, the biocompatible dye may include, but is not limited to, E124, fluorescein isothiocyanate (FITC), 4’,6-diamidino-2-phenylindole (DAPI), methylene blue, erythrosine B, ponceau S, alura red, SYBR green, alcian blue, brilliant blue G, calcein blue, cardio green, crystal violet, nile blue, india ink, brilliant blue, indigo carmine, Sudan III, methyl green, oil red, pyronin Y, tattoo ink, purpurin, phloxine B, picric acid, carbon nanotubes, a fuchsin, resazurin, a trichrome, or a combination of any two or more thereof.
[0042] In any embodiment herein, the inner core may further include powders, porous matrices, or combinations thereof. Such powders in any embodiment herein, for example, may include freeze-dried collagen/ORC in powder form. Such porous matrix materials may include a freeze-dried collagen/ORC matrix.
Features of the Outer Laver and/or Inner Core
[0043] In any embodiment disclosed herein, the collagen of the outer layer and/or the inner core may include a mammalian collagen, such as a bovine collagen, a human collagen, or a combination thereof. The collagen of any embodiment herein may be a Type I collagen, a Type II collagen, a Type III collagen, may be obtained from any natural source, may be chemically-modified collagen ( e.g ., an atelocollagen obtained by removing the immunogenic telopeptides from natural collagen), or may be a combination of any two or more thereof. For example, the collagen may include collagen obtained from bovine corium that has been rendered largely free of non-collagenous components, for example, including fat, non- collagenous proteins, polysaccharides, and other carbohydrates, such as by procedures described in U.S. Pat. Nos. 4,614,794 and 4,320,201, each of which is incorporated herein by reference. The bovine collagen may include one or both of bovine collagen type I and bovine collagen type III. In any embodiment disclosed herein, the outer layer and/or inner core may include a weight ratio of human collagen type I to human collagen type III of about 100:0, about 90: 10, about 80:20, about 70:30, about 60:40, about 50:50, about 40:60, about 30:70, about 20:80, about 10:90, about 0: 100, or any range including and/or in between any two of these values. The ratio by weight of human collagen type I to human collagen type III may be greater than about 50:50, or greater than about 70:30. The collagen of any embodiment herein may include a weight ratio of type I bovine collagen to type III bovine collagen of about 95:5, about 85: 15, about 75:25, about 65:35, about 55:45, about 50:50, about 45:55, about 65:35, about 75:25, about 85: 15, about 95:5, or any range including and/or in between
any two of these values. The ratio by weight of the type I bovine collagen to type III bovine collagen may be about 85: 15.
[0044] The amount of collagen included in the outer layer and/or the inner core of any embodiment herein may be about 30 wt.% to 100 wt.%. Thus, the amount of collagen may be about 30 wt.%, about 32 wt.%, about 34 wt.%, about 36 wt.%, about 38 wt.%, about 40 wt.%, about 42 wt.%, about 44 wt.%, about 46 wt.%, about 48 wt.%, about 50 wt.%, about 52 wt.%, about 54 wt.%, about 56 wt.%, about 58 wt.%, about 60 wt.%, about 62 wt.%, about 64 wt.%, about 66 wt.%, about 68 wt.%, about 70 wt.%, about 72 wt.%, about 74 wt.%, about 76 wt.%, about 78 wt.%, about 80 wt.%, about 82 wt.%, about 84 wt.%, about 86 wt.%, about 88 wt.%, about 90 wt.%, about 92 wt.%, about 94 wt.%, about 95 wt.%, about 96 wt.%, about 97 wt.%, about 98 wt.%, about 99 wt.%, or any range including and/or in between any two of these values.
[0045] The collagen included in the outer layer and/or the inner core of any embodiment herein may have a weight-average molecular weight of about 5,000, about 6,000, about 7,000, about 8,000, about 9,000, about 10,000, about 12,000, about 14,000, about 16,000, about 18,000, about 20,000, about 22,000, about 24,000, about 26,000, about 28,000, about 30,000, about 32,000, about 34,000, about 36,000, about 38,000, about 40,000, about 45,000, about 50,000, about 55,000, about 60,000, about 65,000, about 70,000, about 75,000, about 80,000, about 85,000, about 90,000, about 95,000, about 100,000, or any range including and/or in between any two of these values.
[0046] As discussed above, the outer layer and/or the inner core may include ORC. ORC may be produced by the oxidation of cellulose, for example with dinitrogen tetroxide and/or as described in U.S. Pat. No. 3,122,479 (incorporated herein by reference). Not intending to be bound by theory, it is believed that this process may convert primary alcohol groups on the saccharide residues of the cellulose to carboxylic acid groups, for example, forming uronic acid residues within the cellulose chain. The oxidation may not proceed with complete selectivity, and as a result hydroxyl groups on carbons 2 and 3 of the saccharide residue may be converted to the keto form. These ketone units may introduce an alkali labile link, which at pH 7 or higher initiates the decomposition of the polymer via formation of a lactone and sugar ring cleavage. As a result, oxidized regenerated cellulose is biodegradable and bioresorbable under physiological conditions. ORC is available with a variety of degrees of oxidation and hence rates of degradation. The ORC may include particles, fibers, or both; in
any embodiment disclosed herein, the ORC may be in the form of particles, such as fiber particles or powder particles. In embodiments that include ORC fibers, the ORC fibers may have a volume fraction such that at least 80% of the fibers have lengths in the range from about 5 pm to about 1000 pm, or from about 250 pm to about 450 pm.
[0047] The outer layer and/or the inner core of any embodiment herein may include about 30 wt.% to about 70 wt.% ORC (for the outer layer, this may be crosslinked ORC) with a weight-average molecular weight of about 50,000 to about 1,000,000. Thus, the ORC of any embodiment disclosed herein may be included in an amount of about 30 wt.%, about 32 wt.%, about 34 wt.%, about 36 wt.%, about 38 wt.%, about 40 wt.%, about 42 wt.%, about 44 wt.%, about 46 wt.%, about 48 wt.%, about 50 wt.%, about 52 wt.%, about 54 wt.%, about 56 wt.%, about 58 wt.%, about 60 wt.%, about 62 wt.%, about 64 wt.%, about 66 wt.%, about 68 wt.%, about 70 wt.%, or any range including and/or in between any two of these values. The ORC may have a weight-average molecular weight of about 50,000, about 100,000, about 150,000, about 200,000, about 250,000, about 300,000, about 350,000, about 400,000, about 450,000, about 500,000, about 550,000, about 600,000, about 650,000, about 700,000, about 750,000, about 800,000, about 850,000, about 900,000, about 950,000, about 1,000,000, or any range including and/or in between any two of these values.
[0048] In any embodiment herein including one or more of collagen and chitosan along with ORC in the outer layer and/or the inner core, a weight ratio of the one or more of collagen and chitosan to ORC may be about 60:40 to about 40:60 in the outer layer and/or the inner core. The weight ratio of the one or more of collagen and chitosan to ORC may be about 60:40, about 59:41, about 58:42, about 57:43, about 56:44, about 55:45, about 54:46, about 53:47, about 52:48, about 51 :49, about 50:50, about 49:51, about 48:52, about 47:53, about 46:54, about 45:55, about 44:56, about 43:57, about 42:58, about 41 :59, about 40:60, or any range including and/or in between any two of these values.
[0049] In any embodiment disclosed herein, the outer layer and/or the inner core may include about 0.001 wt.% to about 5 wt.% of an antimicrobial agent. Thus, the total amount of antimicrobial agent(s) in the outer layer and/or the inner core may independently for each be about 0.001 wt.%, about 0.002 wt.%, about 0.003 wt.%, about 0.004 wt.%, about 0.005 wt.%, about 0.006 wt.%, about 0.007 wt.%, about 0.008 wt.%, about 0.009 wt.%, about 0.01 wt.%, about 0.02 wt.%, about 0.03 wt.%, about 0.04 wt.%, about 0.05 wt.%, about 0.06 wt.%, about 0.07 wt.%, about 0.08 wt.%, about 0.09 wt.%, about 0.1 wt.%, about 0.2 wt.%, about 0.3 wt.%, about 0.4 wt.%, about 0.5 wt.%, about 0.6 wt.%, about 0.7 wt.%, about 0.8 wt.%,
about 0.9 wt.%, about 1 wt.%, about 2 wt.%, about 3 wt.%, about 4 wt.%, about 5 wt.%, or any range including and/or in between any two of these values. The antimicrobial agent may include a penicillin, a streptomycin, ionic silver (or a source for ionic silver), chlorhexidine, a poly(hexamethylene biguanide) (PHMB), iodine, or a combination of any two or more thereof. Suitable sources of ionic silver may include ionic silver in a variety of forms including as pharmaceutically acceptable salts, where representative examples include but are not limited to silver oxide, silver chromate, silver allantoinate, silver borate, silver glycerolate, silver nitrate, silver acetate, silver chloride, silver sulfate, silver lactate, silver bromide, silver iodide, silver carbonate, silver citrate, silver laurate, silver deoxycholate, silver salicylate, silver / -ami nobenzoate, silver -aminosalicylate, or a combination of any two or more thereof. In addition, while ionic silver (or a source thereof) may initially be incorporated into the outer layer and/or inner core as a silver salt, at least a portion (if not substantially all) of the ionic silver may be complexed to, e.g ., ORC, in the outer layer and/or the inner core.
[0050] The outer layer and inner core may contain varying concentration of any of the above referenced materials (e.g, biopolymers, plasticizers, antimicrobial agents, and/or additional materials as described herein in any embodiment). For example, in any embodiment, the outer layer may include about 50 wt.% to about 100 wt.% gelatin and the inner core may include intact collagen, such that the inner core has a higher concentration of collagen than the outer layer. In any embodiment herein, both the outer layer and inner core may include one or more antimicrobial agents as described herein, where the outer layer may include a higher concentration of antimicrobial agents than the inner core. In any
embodiment herein, both the outer layer and inner core may include one or more
antimicrobial agents as described herein, where the outer layer may include a lower concentration of antimicrobial agents than the inner core.
The Wound Insert
[0051] As provided previously, the present disclosure provides a wound insert that includes an outer layer and an inner core. The outer layer may include a outward-facing side and an inner-core facing side. In any embodiment disclosed herein, an exterior surface of the inner core may be adjoined with the inner core-facing side of the outer layer.
[0052] In any embodiment disclosed herein, the wound insert of the present technology may be in the shape of a cylinder, a sphere, a cube, a cuboid, a hexagonal prism, a cone, a square-based pyramid, triangular-based pyramid, or a triangular prism. For example, the wound insert of the present technology may be in the shape of a cylinder, a cylinder with at least one rounded edge, cuboid, or a cuboid with at least one rounded edge. In any embodiment herein, the wound insert may be in the shape of a cylinder, wherein the cylindrical wound insert further comprises a hemispherical compartment on each end of the wound insert (see FIGs. 1 A-1B). In any embodiment herein, the wound insert may be in the shape of a cuboid with one or more rounded edges, wherein the cuboid wound insert further comprises a cubed compartment on each end of the wound insert (see FIGs. 2A-2B).
[0053] In any embodiment disclosed herein, the length of the wound insert of the present technology compared to the width may be from about 15: 1 to about 15:6. For example, in any embodiment herein, the length to width ratio may be about 15: 1, about 15:2, about 15:3, about 15:4, about 15:5, about 15:6, or any range including and/or in between any two of the preceding values. In any embodiment disclosed herein, the width to height ratio of the wound insert according to the present technology may be about 3:2 to 2:3. For example, in any embodiment herein, the width to height ratio may be about 3 :2, about 3: 1, about 2: 1, about 1 : 1, about 1 :2, about 1 :3, about 2:3, or any range including and/or in between any two of the preceding values.
[0054] In any embodiment disclosed herein, the length of the wound insert of the present technology may be about 1 cm to about 10 cm. Thus, the length of the wound insert may be about 1 cm, about 1.1 cm, about 1.2 cm, about 1.3 cm, about 1.4 cm, about 1.5 cm, about 1.6 cm, about 1.7 cm, about 1.8 cm, about 1.9 cm, about 2.0 cm, about 2.2 cm, about 2.4 cm, about 2.6 cm, about 2.8 cm, about 3.0 cm, about 3.2 cm, about 3.4 cm, about 3.6 cm, about 3.8 cm, about 4.0 cm, about 4.2 cm, about 4.4 cm, about 4.6 cm, about 4.8 cm, about 5.0 cm, about 5.5 cm, about 6.0 cm, about 6.5 cm, about 7.0 cm, about 7.5 cm, about 8.0 cm, about 8.5 cm, about 9.0 cm, about 9.5 cm, about 10.0 cm, or any range including and/or in between any two of these values.
[0055] In any embodiment disclosed herein, the width and/or height of the wound insert of the present technology may be about 0.1 cm to about 3 cm. Thus, the width and/or height of the wound insert may be about 0.1 cm, about 0.2 cm, about 0.3 cm, about 0.4 cm, about 0.5 cm, about 0.6 cm, about 0.7 cm, about 0.8 cm, about 0.9 cm, about 1.0 cm, about 1.1 cm,
about 1.2 cm, about 1.3 cm, about 1.4 cm, about 1.5 cm, about 1.6 cm, about 1.7 cm, about 1.8 cm, about 1.9 cm, about 2.0 cm, about 2.1 cm, about 2.2 cm, about 2.3 cm, about 2.4 cm, about 2.5 cm, about 2.6 cm, about 2.7 cm, about 2.8 cm, about 2.9 cm, about 3.0 cm, or any range including and/or in between any two of these values.
[0056] In any embodiment disclosed herein, the wound insert of the present technology may comprise perforations to facilitate tissue integration. The perforations of the wound insert may be about 0.1 mM to about 100 mM in width and/or height. The perforations of the wound insert may be about 0.1 pM to about 100 pM deep. The perforations of the wound insert may be through the entire thickness of the outer layer. FIG. 3 provides an illustrative side view illustration of a wound insert 300 that includes an outer layer 301, an inner core 302, and a plurality of perforations 303.
[0057] In any embodiment disclosed herein, the wound insert of the present technology may comprise through-holes through the entire width, height, and/or length of the wound insert, such as for beneficial use of the wound insert in negative pressure therapy. The through-holes of the wound insert may be about 2 mm to about 8 mm in width and/or height. Thus, the through-holes of the wound insert may be about 2 mm, about 2.2 mm, about 2.4 mm, about 2.6 mm, about 2.8 mm, about 3 mm, about 3.2 mm, about 3.4 mm, about 3.6 mm, about 3.8 mm, about 4 mm, about 4.2 mm, about 4.4 mm, about 4.6 mm, about 4.8 mm, about 5 mm, about 5.5 mm, about 6 mm, about 6.5 mm, about 7 mm, about 7.5 mm, about 8 mm, or any range including and/or in between any two of these values. FIG. 4 provides an illustrative side view illustration of a wound insert 400 that includes an outer layer 401, inner core 402, and a plurality of through-holes 403.
[0058] In any embodiment disclosed herein, the wound insert of the present disclosure may be sterile and packaged in a microorganism-impermeable container.
Negative-Pressure Therapy
[0059] The wound insert of any embodiment described herein may be employed in therapy in which a wound is treated with reduced pressure. Treatment of a wound with reduced pressure may be commonly referred to as“negative-pressure therapy,” but is also known by other names, including“negative-pressure wound therapy,”“reduced-pressure therapy,” “vacuum therapy,”“vacuum-assisted closure,” and“topical negative-pressure,” for example. Negative-pressure therapy may provide a number of benefits, including migration of
epithelial and subcutaneous tissues, improved blood flow, and/or micro-deformation of tissue at a wound site. Together, these benefits may increase development of granulation tissue and reduce healing times.
[0060] Generally, the system may be configured to provide negative-pressure to a wound in accordance with this specification. In any embodiment herein, the system may generally include a negative-pressure supply, and may include or be configured to be coupled to a distribution component. In general, a distribution component may refer to any
complementary or ancillary component configured to be fluidly coupled to a negative- pressure supply in a fluid path between a negative-pressure supply and a wound.
[0061] In any embodiment herein, the wound insert may be configured to distribute negative pressure. Additionally or alternatively, the fluid path(s) may be reversed or a secondary fluid path may be provided to facilitate movement of fluid across a wound.
Additionally or alternatively, the fluid pathways of the through-holes may be interconnected to improve distribution or collection of fluids.
[0062] The fluid mechanics associated with using a negative-pressure source to reduce pressure in another component or location, such as within a sealed therapeutic environment, can be mathematically complex. However, the basic principles of fluid mechanics applicable to negative-pressure therapy are generally well-known to those skilled in the art. The process of reducing pressure may be described generally and illustratively herein as“delivering,” “distributing,” or“generating” negative pressure, for example.
[0063] In general, a fluid, such as wound fluid (for example, wound exudates and other fluids), flows toward lower pressure along a fluid path. Thus, the term“downstream” typically implies something in a fluid path relatively closer to a source of negative pressure or further away from a source of positive pressure. Conversely, the term“upstream” implies something relatively further away from a source of negative pressure or closer to a source of positive pressure. This orientation is generally presumed for purposes of describing various features and components herein. However, the fluid path may also be reversed in some applications (such as by substituting a positive-pressure source for a negative-pressure source) and this descriptive convention should not be construed as a limiting convention.
[0064] “Negative pressure” may generally refer to a pressure less than a local ambient pressure, such as the ambient pressure in a local environment external to a sealed therapeutic
environment provided by the wound insert. In many cases, the local ambient pressure may also be the atmospheric pressure proximate to or about a wound. Alternatively or
additionally, the pressure may be less than a hydrostatic pressure associated with the tissue at the wound. While the amount and nature of negative pressure applied to a wound may vary according to therapeutic requirements, the pressure is generally a low vacuum, also commonly referred to as a rough vacuum, between -5 mm Hg (-667 Pa) and -500 mm Hg (- 66.7 kPa), gauge pressure. Common therapeutic ranges are between -50 mm Hg (-6.7 kPa) and -300 mm Hg (-39.9 kPa), gauge pressure.
[0065] Additionally or alternatively, in any embodiment herein, a negative-pressure supply may be a reservoir of air at a negative pressure, or may be a manual or electrically-powered device that can reduce the pressure in a sealed volume, such as a vacuum pump, a suction pump, a wall suction port available at many healthcare facilities, or a micro-pump, for example. A negative-pressure supply may be housed within or used in conjunction with other components, such as sensors, processing units, alarm indicators, memory, databases, software, display devices, or user interfaces that further facilitate therapy. A negative- pressure source may be combined with a controller and other components into a therapy unit. A negative-pressure supply may also have one or more supply ports configured to facilitate coupling and de-coupling of the negative-pressure supply to one or more distribution components.
[0066] In any embodiment herein, components may be fluidly coupled to each other to provide a path for transferring fluids (i.e., liquid and/or gas) between the components. For example, components may be fluidly coupled through a fluid conductor, such as a tube. As used herein, the term“fluid conductor” may include a tube, pipe, hose, conduit, or other structure with one or more lumina or open passages adapted to convey a fluid between two ends thereof. Typically, a fluid conductor may be an elongated, cylindrical structure with some flexibility, but the geometry and rigidity may vary. Additionally or alternatively, in any embodiment herein, the negative-pressure source may be operatively coupled to the wound insert via an interface.
Treatment Methods of the Present Technology
[0067] In an aspect, methods for treating a wound in a subject in need thereof are provided, wherein the method includes administering a wound insert of any embodiment disclosed
herein to the wound. The wound may be a tunneling wound, a dermal wound, a diabetic wound, an acute wound, a chronic wound, or a combination of any two or more thereof. Exemplary chronic wounds include, but are not limited to, infectious wounds, venous ulcers, decubitus ulcers, or diabetic ulcers. In any embodiment herein, the wound is a tunneling wound. The method may include administering two or more wound inserts to the wound.
[0068] The wound insert may be administered directly to the wound. Any method known to those in the art for administering a wound insert to a tunneling wound, a dermal wound, a diabetic wound, an acute wound, or a chronic wound disclosed herein may be employed. Suitable methods include in vitro or in vivo methods. In vivo methods typically include the administration of one or more wound inserts to a subject in need thereof, suitably a human. When used in vivo for therapy, the one or more wound inserts described herein are administered to the subject in effective amounts (i.e., amounts that have desired therapeutic effect). The dose and dosage regimen will depend upon the state of the wound of the subject and the characteristics of the particular wound insert used.
[0069] The effective amount may be determined during pre-clinical trials and clinical trials by methods familiar to physicians and clinicians. An effective amount of one or more wound inserts useful in the methods may be administered to a subject in need thereof by any number of well-known methods for administering wound inserts.
[0070] In any embodiment disclosed herein, the wound inserts may be administered daily for 1 hour or more, for 2 hours or more, for 3 hours or more, for 4 hours or more, for 5 hours or more, for 6 hours or more, or for 12 hours or more. In any embodiment disclosed herein, the wound inserts may be administered one, two, three, four, or five times per day. In any embodiment disclosed herein, the wound inserts may be administered daily for one, two, three, four, or five weeks. In any embodiment disclosed herein, the wound inserts may be administered daily for less than 6 weeks. In any embodiment disclosed herein, the wound inserts may be administered daily for 6 weeks or more. In any embodiment disclosed herein, the wound inserts may be administered daily for 12 weeks or more. In any embodiment disclosed herein, the wound inserts may be administered every day, every other day, every third day, every fourth day, every fifth day, or every sixth day. In any embodiment disclosed herein, the wound inserts may be administered weekly, bi-weekly, tri-weekly, or monthly. In any embodiment disclosed herein, the wound inserts may be administered for a chronic wound as appropriate.
[0071] In any embodiment herein, the method may include employing the wound insert in the context of a negative-pressure therapy, where the negative-pressure therapy may include positioning the wound insert in and/or proximate to the wound. The negative-pressure therapy may further include sealing the wound insert to tissue surrounding the wound to form a sealed space. For example, the wound insert may be positioned in and/or proximate to the wound and sealed to an attachment surface near the wound, for example, to undamaged epidermis peripheral to a wound.
[0072] The negative-pressure therapy method in any embodiment herein may further include fluidly coupling a negative-pressure source to the sealed space and operating the negative-pressure source to generate a negative pressure in the sealed space. For example, the negative-pressure source may be coupled to the wound insert such that the negative- pressure source may be used to reduce the pressure in the sealed space. For example, negative pressure applied across the wound, for example, via the wound insert may be effective to induce macrostrain and microstrain at the wound site, as well as remove exudates and other fluids from the wound.
Methods of Manufacturing a Wound Insert of the Present Technology
[0073] In a further related aspect, a method of manufacturing a wound insert of any embodiment of the present technology is provided, where the method includes: fabricating an outer layer of the wound insert from a first slurry comprising one or more biopolymers, wherein the outer layer is in a shape having a hollow center; photo-crosslinking and/or reagent-crosslinking the outer layer to obtain one or more photocrosslinked and/or reagent- crosslinked biopolymers; drying the outer layer of the wound insert; depositing a second slurry into the hollow center of the outer layer to form an inner core of the wound insert; and removing residual moisture from the inner core, where the shape of the outer layer may be a cylinder, a sphere, a cube, a cuboid, a hexagonal prism, a cone, a square-based pyramid, triangular-based pyramid, or a triangular prism; the second slurry includes a biopolymer; the outer layer exhibits a modulus of elasticity from about 0.5 MPa to about 5.0 MPa; and the inner core exhibits a lower modulus of elasticity than the outer layer.
[0074] In any embodiment herein, the fabricating may include extrusion of the first slurry to fabricate the outer layer. For example, in any embodiment herein, the first slurry may be extruded via a die having a hollow center to obtain a shape ( e.g ., a tube structure). As
disclosed herein, the outer layer shape (i.e., tube structure) may be a cylinder, a sphere, a cube, a cuboid, a hexagonal prism, a cone, a square-based pyramid, triangular-based pyramid, or a triangular prism.
[0075] In any embodiment herein, the first slurry may have a pH from about 3 to 7. For example, in any embodiment herein, the first slurry may have a pH of about 3, about 3.5, about 4, about 4.5, about 5, about 5.5, about 6, about 6.5, about 7, or any range including and/or in between any two or more of the preceding values. In any embodiment herein, the pH of the first slurry may be from about 4.5 to about 5.5.
[0076] In any embodiment disclosed herein, the first slurry may further include at least one plasticizer as described herein in any embodiment. The at least one plasticizer may be included in the amount of about 2 wt.% to about 30 wt.% within the first slurry. Thus, the at least one plasticizer may be included in the amount of about 2 wt.%, about 3 wt.%, about 4 wt.%, about 5 wt.%, about 6 wt.%, about 7 wt.%, about 8 wt.%, about 9 wt.%, about 10 wt.%, about 11 wt.%, about 12 wt.%, about 13 wt.%, about 14 wt.%, about 15 wt.%, about 16 wt.%, about 17 wt.%, about 18 wt.%, about 19 wt.%, about 20 wt.%, about 21 wt.%, about 22 wt.%, about 23 wt.%, about 24 wt.%, about 25 wt.%, about 26 wt.%, about 27 wt.%, about 28 wt.%, about 29 wt.%, about 30 wt.%, or any range including and/or in between any two of these values.
[0077] In any embodiment herein, the first slurry and/or second slurry correspond to the resultant outer layer and/or inner core, respectively. In any embodiment herein, the first slurry and/or second slurry may include one or more biopolymers including, but not limited to, a collagen, an oxidized cellulose, an oxidized regenerated cellulose (ORC), a
polysaccharide, a chitosan, a gelatin, hyaluronic acid, or a combination of any two or more thereof. In any embodiment disclosed herein, the collagen of the first slurry and/or the second slurry may include a mammalian collagen, such as a bovine collagen, a human collagen, or a combination thereof as described herein in any embodiment.
[0078] The amount of collagen included in the first slurry and/or the second slurry of any embodiment herein may be about 30 wt.% to 100 wt.% as described herein in any
embodiment. Thus, the amount of collagen may be about 30 wt.%, about 32 wt.%, about 34 wt.%, about 36 wt.%, about 38 wt.%, about 40 wt.%, about 42 wt.%, about 44 wt.%, about 46 wt.%, about 48 wt.%, about 50 wt.%, about 52 wt.%, about 54 wt.%, about 56 wt.%, about 58 wt.%, about 60 wt.%, about 62 wt.%, about 64 wt.%, about 66 wt.%, about 68 wt.%, about 70
wt.%, about 72 wt.%, about 74 wt.%, about 76 wt.%, about 78 wt.%, about 80 wt.%, about 82 wt.%, about 84 wt.%, about 86 wt.%, about 88 wt.%, about 90 wt.%, about 92 wt.%, about 94 wt.%, about 95 wt.%, about 96 wt.%, about 97 wt.%, about 98 wt.%, about 99 wt.%, or any range including and/or in between any two of these values.
[0079] The collagen included in the first slurry and/or second slurry of any embodiment herein may have a weight-average molecular weight of about 5,000, about 6,000, about 7,000, about 8,000, about 9,000, about 10,000, about 12,000, about 14,000, about 16,000, about 18,000, about 20,000, about 22,000, about 24,000, about 26,000, about 28,000, about 30,000, about 32,000, about 34,000, about 36,000, about 38,000, about 40,000, about 45,000, about 50,000, about 55,000, about 60,000, about 65,000, about 70,000, about 75,000, about 80,000, about 85,000, about 90,000, about 95,000, about 100,000, or any range including and/or in between any two of these values.
[0080] As discussed above, the first slurry and/or second slurry may include ORC as described herein in any embodiment. The first slurry and/or the second slurry of any embodiment herein may include about 30 wt.% to about 70 wt.% ORC (for the outer layer, this may be crosslinked ORC) with a weight-average molecular weight of about 50,000 to about 1,000,000. Thus, the ORC of any embodiment disclosed herein may be included in an amount of about 30 wt.%, about 32 wt.%, about 34 wt.%, about 36 wt.%, about 38 wt.%, about 40 wt.%, about 42 wt.%, about 44 wt.%, about 46 wt.%, about 48 wt.%, about 50 wt.%, about 52 wt.%, about 54 wt.%, about 56 wt.%, about 58 wt.%, about 60 wt.%, about 62 wt.%, about 64 wt.%, about 66 wt.%, about 68 wt.%, about 70 wt.%, or any range including and/or in between any two of these values. The ORC may have a weight-average molecular weight of about 50,000, about 100,000, about 150,000, about 200,000, about 250,000, about
300,000, about 350,000, about 400,000, about 450,000, about 500,000, about 550,000, about 600,000, about 650,000, about 700,000, about 750,000, about 800,000, about 850,000, about 900,000, about 950,000, about 1,000,000, or any range including and/or in between any two of these values.
[0081] In any embodiment herein including one or more of collagen and chitosan along with ORC in the first slurry and/or second slurry, a weight ratio of the one or more of collagen and chitosan to ORC may be about 60:40 to about 40:60 in the first slurry and/or the second slurry. The weight ratio of the one or more of collagen and chitosan to ORC may be about 60:40, about 59:41, about 58:42, about 57:43, about 56:44, about 55:45, about 54:46,
about 53 :47, about 52:48, about 51 :49, about 50:50, about 49:51, about 48:52, about 47:53, about 46:54, about 45:55, about 44:56, about 43 :57, about 42:58, about 41 :59, about 40:60, or any range including and/or in between any two of these values.
[0082] In any embodiment disclosed herein, the first slurry and/or second slurry may include about 0.001 wt.% to about 5 wt.% of an antimicrobial agent as described herein in any embodiment. Thus, the total amount of antimicrobial agent(s) in the outer layer and/or the inner core may independently for each be about 0.001 wt.%, about 0.002 wt.%, about 0.003 wt.%, about 0.004 wt.%, about 0.005 wt.%, about 0.006 wt.%, about 0.007 wt.%, about 0.008 wt.%, about 0.009 wt.%, about 0.01 wt.%, about 0.02 wt.%, about 0.03 wt.%, about 0.04 wt.%, about 0.05 wt.%, about 0.06 wt.%, about 0.07 wt.%, about 0.08 wt.%, about 0.09 wt.%, about 0.1 wt.%, about 0.2 wt.%, about 0.3 wt.%, about 0.4 wt.%, about 0.5 wt.%, about 0.6 wt.%, about 0.7 wt.%, about 0.8 wt.%, about 0.9 wt.%, about 1 wt.%, about 2 wt.%, about 3 wt.%, about 4 wt.%, about 5 wt.%, or any range including and/or in between any two of these values.
[0083] Following fabrication of the outer layer, the method may further include treating the outer layer with a weak basic gas. For example, in any embodiment herein, the weak gas may be ammonia.
[0084] As disclosed above, the method includes photocrosslinking and/or reagent crosslinking the outer layer to obtain one or more crosslinked biopolymers. Photo
crosslinking may be carried out by exposing the outer layer to light with a wavelength from about 360 nm to about 370 nm. The total radiant power of all wavelengths of light used to crosslink the one or more biopolymers of the outer layer may be from about 10 mW/cm2 to about 1000 mW/cm2. Thus, the total radiant power of all wavelengths of light used to crosslink the biopolymer of the outer layer may be from about 10 mW/cm2, about 15 mW/cm2, about 20 mW/cm2, about 25 mW/cm2, about 30 mW/cm2, about 35 mW/cm2, about 40 mW/cm2, about 45 mW/cm2, about 50 mW/cm2, about 55 mW/cm2, about 60 mW/cm2, about 65 mW/cm2, about 70 mW/cm2, about 75 mW/cm2, about 80 mW/cm2, about 85 mW/cm2, about 90 mW/cm2, about 95 mW/cm2, about 100 mW/cm2, about 110 mW/cm2, about 120 mW/cm2, about 130 mW/cm2, about 140 mW/cm2, about 150 mW/cm2, about 160 mW/cm2, about 170 mW/cm2, about 180 mW/cm2, about 190 mW/cm2, about 200 mW/cm2, about 210 mW/cm2, about 220 mW/cm2, about 230 mW/cm2, about 240 mW/cm2, about 250 mW/cm2, about 260 mW/cm2, about 270 mW/cm2, about 280 mW/cm2, about 290 mW/cm2,
about 300 mW/cm2, about 310 mW/cm2, about 320 mW/cm2, about 330 mW/cm2, about 340 mW/cm2, about 350 mW/cm2, about 360 mW/cm2, about 370 mW/cm2, about 380 mW/cm2, about 390 mW/cm2, about 400 mW/cm2, about 410 mW/cm2, about 420 mW/cm2, about 430 mW/cm2, about 440 mW/cm2, about 450 mW/cm2, about 460 mW/cm2, about 470 mW/cm2, about 480 mW/cm2, about 490 mW/cm2, about 500 mW/cm2, about 550 mW/cm2, about 600 mW/cm2, about 650 mW/cm2, about 750 mW/cm2, about 800 mW/cm2, about 850 mW/cm2, about 900 mW/cm2, about 950 mW/cm2, about 1000 mW/cm2, or any range including and/or in between any two of these values. The biopolymer of the outer layer may be photo- crosslinked with light for a period of about 1 minute to about 100 minutes.
[0085] Reagent-crosslinking may be carried out by cross-linking compounds, where part of the cross-linking compound is incorporated into the biopolymer to generate reagent- crosslinked biopolymers as described herein. Exemplary reagent-crosslinked biopolymers are biopolymers crosslinked by one or more of disuccinimidyl suberate (DSS),
disuccinimidyl tartrate (DST), dithiobis succinimidyl propionate (DSP), bismaleimidoethane (BMOE), dithiobismaleimidoethane (DTME), m-m al ei i dobenzoy 1 -/V-hy droxy sued ni mi de ester (MBS), L-g-mal eimi dobutyryl -oxy sued ni mi de ester (GMBS), N-e- maleimidocaproyloxy-succinimide ester (EMCS), and L-e-maleimidocaproyl- oxysulfosuccinimide ester (sulfo-EMCS). Other exemplary reagent-crosslinked biopolymers are biopolymers crosslinked in the presence of light ( e.g ., 250-350 nm light) with N-((2- pyridyldithio)ethyl)-4-azidosalicylamide and/or Af-5-azi do-2-nitrobenzyl oxy succi ni mi de - thus, light may be used to initiate the crosslinking reaction of the cross-linking compound with a biopolymer.
[0086] The drying may be carried out at a temperature from about 20 °C to about 80 °C. Suitable drying temperatures in any embodiment herein may include, but are not limited to, about 20 °C, about 25 °C, about 30 °C, about 35 °C, about 40 °C, about 45 °C, about 50 °C, about 55 °C, about 60 °C, about 65 °C, about 70 °C, about 75 °C, about 80 °C , or any range including and/or in between any two of the preceding values. The drying may be carried out for a duration of about 2 hours to about 24 hours. For example, in any embodiment herein, the drying may be carried out for about 2 hours, about 3 hours, about 4 hour, about 5 hours, about 6 hours, about 7 hours, about 8 hours, about 9 hours, about 10 hours, about 11 hours, about 12 hours, about 13 hours, about 14 hours, about 15 hours, about 16 hours, about 17 hours, about 18 hours, about 19 hours, about 20 hours, about 21 hours, about 22 hours, about
23 hours, about 24 hours, or any range including and/or in between any two of the preceding values.
[0087] In any embodiment herein, depositing the second slurry may include injecting or extruding the second slurry within the outer layer’s hollow center to form the inner core. Following deposition of the second slurry to form the inner core, the method includes removing residual water from the inner core. For example, in any embodiment herein, removing the residual moisture from the inner core may include freeze-drying the inner core. In any embodiment herein, the inner core may retain 0% to about 5% of residual moisture. Suitable amounts of residual moisture may include, but are not limited to, about 0.05%, about 0.1%, about 0.5%, about 1%, about 2%, about 3%, about 4%, about 5%, or any range including and/or in between any two of the preceding values.
[0088] In any embodiment herein, the method may include shaping ( e.g ., hemispherical, cubed, or other suitable shape) excess outer layer to form a fully or partially closed end of the wound insert (see FIGS. 1 A and 2A).
[0089] In a related aspect, the present disclosure provides a wound insert prepared according to the method of manufacturing said wound insert as described herein in any embodiment.
Kits Comprising the Wound Insert of the Present Technology
[0090] In a further related aspect, the present disclosure provides kits that include a wound insert of any embodiment disclosed herein and instructions for use. The kits of the present technology may also include methods for treating a wound in a subject in need thereof. The kit may optionally comprise components such as antiseptic wipes, ointment, adhesive tape, tweezers, scissors, etc.
[0091] The examples herein are provided to illustrate advantages of the present technology and to further assist a person of ordinary skill in the art with preparing or using the compositions and systems of the present technology. The examples should in no way be construed as limiting the scope of the present technology, as defined by the appended claims. The examples can include or incorporate any of the variations, aspects, or embodiments of the present technology described above. The variations, aspects, or embodiments described
above may also further each include or incorporate the variations of any or all other variations, aspects or embodiments of the present technology.
EQUIVALENTS
[0092] While certain embodiments have been illustrated and described, a person with ordinary skill in the art, after reading the foregoing specification, can effect changes, substitutions of equivalents and other types of alterations to the compositions, systems, and methods of the present technology. Each aspect and embodiment described above can also have included or incorporated therewith such variations or aspects as disclosed in regard to any or all of the other aspects and embodiments.
[0093] The present technology is also not to be limited in terms of the particular aspects and embodiments described herein, which are intended as single illustrations of individual aspects of the present technology. Many modifications and variations of this present technology can be made without departing from its spirit and scope, as will be apparent to those skilled in the art. Functionally equivalent methods within the scope of the present technology, in addition to those enumerated herein, will be apparent to those skilled in the art from the foregoing descriptions. Such modifications and variations are intended to fall within the scope of the appended claims. It is to be understood that this present technology is not limited to particular methods, reagents, compounds, compositions, labeled compounds or biological systems, which can, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular aspects only, and is not intended to be limiting. Thus, it is intended that the specification be considered as exemplary only with the breadth, scope and spirit of the present technology indicated only by the appended claims, definitions therein and any equivalents thereof.
[0094] The embodiments, illustratively described herein may suitably be practiced in the absence of any element or elements, limitation or limitations, not specifically disclosed herein. Thus, for example, the terms“comprising,”“including,”“containing,” etc. shall be read expansively and without limitation. Additionally, the terms and expressions employed herein have been used as terms of description and not of limitation, and there is no intention in the use of such terms and expressions of excluding any equivalents of the features shown and described or portions thereof, but it is recognized that various modifications are possible within the scope of the claimed technology. Additionally, the phrase“consisting essentially
of’ will be understood to include those elements specifically recited and those additional elements that do not materially affect the basic and novel characteristics of the claimed technology. The phrase“consisting of’ excludes any element not specified.
[0095] In addition, where features or aspects of the disclosure are described in terms of Markush groups, those skilled in the art will recognize that the disclosure is also thereby described in terms of any individual member or subgroup of members of the Markush group. Each of the narrower species and subgeneric groupings falling within the generic disclosure also form part of the invention. This includes the generic description of the invention with a proviso or negative limitation removing any subject matter from the genus, regardless of whether or not the excised material is specifically recited herein.
[0096] As will be understood by one skilled in the art, for any and all purposes, particularly in terms of providing a written description, all ranges disclosed herein also encompass any and all possible subranges and combinations of subranges thereof. Any listed range can be easily recognized as sufficiently describing and enabling the same range being broken down into at least equal halves, thirds, quarters, fifths, tenths, etc. As a non-limiting example, each range discussed herein can be readily broken down into a lower third, middle third and upper third, etc. As will also be understood by one skilled in the art all language such as“up to,”
“at least,”“down to,” and the like, include the number recited and refer to ranges which can be subsequently broken down into subranges as discussed above. As will also be understood by one skilled in the art all language such as“greater than,”“less than,” and the like, refer to ranges which can be subsequently broken down into subranges as discussed above. Finally, as will be understood by one skilled in the art, a range includes each individual member.
[0097] All publications, patent applications, issued patents, and other documents (for example, journals, articles and/or textbooks) referred to in this specification are herein incorporated by reference as if each individual publication, patent application, issued patent, or other document was specifically and individually indicated to be incorporated by reference in its entirety to the extent they are not inconsistent with the explicit teachings of this specification. Definitions that are contained in text incorporated by reference are excluded to the extent that they contradict definitions in this disclosure.
[0098] Other embodiments are set forth in the following claims, along with the full scope of equivalents to which such claims are entitled.
Claims
1. A wound insert comprising:
an outer layer comprising one or more of a photocrosslinked and a reagent- crosslinked biopolymer; and
an inner core comprising a biopolymer; and
wherein
the outer layer exhibits a modulus of elasticity from about 0.5 MPa to about 5.0 MPa; and
the inner core exhibits a lower modulus of elasticity than the outer layer.
2. The wound insert of claim 1, wherein the wound insert further comprises a suture thread connected to and extending from the outer layer.
3. The wound insert of claim 2, wherein the suture thread is bioresorbable suture thread.
4. The wound insert of claim 2 or claim 3, wherein the suture thread is bioresorbable suture thread comprising a poly(glycolic acid), a poliglycaprone, a polydioxanone, a collagen, or a combination of any two or more thereof.
5. The wound insert of any one of claims 1-4, wherein the wound insert is in a shape
comprising a cylinder, a cylinder with at least one rounded edge, a cuboid, or a cuboid with at least one rounded edge.
6. The wound insert of any one of claims 1-5, wherein the wound insert is in a shape
comprising a cylinder with hemispherical shaped ends.
7. The wound insert of any one of claims 1-6, wherein the width and/or height of the wound insert is about 0.1 cm to about 3 cm.
8. The wound insert of any one of claims 1-7, wherein the width and/or height of the wound insert is about 0.5 cm to about 1.5 cm.
9. The wound insert of any one of claims 1-8, wherein the length of the wound insert is about 1 cm to about 10 cm.
10. The wound insert of any one of claims 1-9, wherein the length of the wound insert is about 2 cm to about 5 cm.
11. The wound insert of any one of claims 1-10, wherein the thickness of the outer layer is about 20 mih to about 300 mih.
12. The wound insert of any one of claims 1-11, wherein the thickness of the outer layer is about 40 mih to about 120 mih.
13. The wound insert of any one of claims 1-12, wherein the wound insert comprises
perforations in at least the outer layer.
14. The wound insert of any one of claims 1-13, wherein the wound insert comprises
through-holes through the entire insert.
15. The wound insert of claim 14, wherein the through-holes have a width and/or height of about 2 mm to about 8 mm.
16. The wound insert of any one of claims 1-15, wherein the one or more of the
photocrosslinked and the reagent-crosslinked biopolymer of the outer layer comprises a collagen, an oxidized cellulose, an oxidized regenerated cellulose (ORC), a
polysaccharide, a chitosan, a gelatin, hyaluronic acid, or a combination of any two or more thereof.
17. The wound insert of any one of claims 1-16, wherein the photocrosslinked and the
reagent-crosslinked biopolymer of the outer layer comprises collagen and ORC.
18. The wound insert of any one of claims 1-16, wherein the photocrosslinked and the
reagent-crosslinked biopolymer of the outer layer comprises collagen, ORC, and gelatin.
19. The wound insert of any one of claims 1-18, wherein the outer layer comprises about 0.01 wt.% to about 100 wt.% of the one or more of the photocrosslinked and the reagent- crosslinked biopolymer.
20. The wound insert of any one of claims 1-19, wherein the outer layer comprises
photocrosslinked biopolymer.
21. The wound insert of any one of claims 1-20, wherein the outer layer comprises at least one plasticizer.
22. The wound insert of any one of claims 1-21, wherein the outer layer comprises about 2 wt.% to about 30 wt.% at least one plasticizer.
23. The wound insert of claim 21 or claim 22, wherein the at least one plasticizer comprises an acetylated monoglyceride, an alkyl citrate, methyl ricinoleate, glycerol, or a combination of any two or more thereof.
24. The wound insert of claim 23, wherein the alkyl citrate is triethyl citrate, acetyl triethyl citrate, tributyl citrate, acetyl tributyl citrate, trioctyl citrate, acetyl trioctyl citrate, trihexyl citrate, acetyl trihexyl citrate, butyryl trihexyl citrate, trimethyl citrate, or a combination of any two or more thereof.
25. The wound insert of any one of claims 1-24, wherein the outer layer comprises collagen, ORC, and glycerol.
26. The wound insert of any one of claims 1-25, wherein the outer layer comprises collagen, ORC, gelatin, and glycerol.
27. The wound insert of any one of claims 1-26, wherein the outer layer comprises 0.001 wt.% to about 5 wt.% of an antimicrobial agent.
28. The wound insert of any one of claims 1-27, wherein the outer layer comprises 0.001 wt.% to about 5 wt.% ionic silver.
29. The wound insert of any one of claims 1-28, wherein the biopolymer of the inner core comprises a collagen, an oxidized cellulose, an oxidized regenerated cellulose (ORC), a polysaccharide, a chitosan, a gelatin, hyaluronic acid, or a combination of any two or more thereof.
30. The wound insert of any one of claims 1-29, wherein the inner core comprises one or more of collagen and chitosan along with ORC, wherein a weight ratio of the one or more of collagen and chitosan to ORC is about 60:40 to about 40:60.
31. The wound insert of any one of claims 1-30, wherein the inner core comprises about 10 wt.% to about 100 wt.% of the biopolymer.
32. The wound insert of any one of claims 1-31, wherein the inner core comprises 0.001 wt.% to about 5 wt.% of an antimicrobial agent.
33. The wound insert of any one of claims 1-32, wherein the inner core comprises 0.001 wt.% to about 5 wt.% of a source for ionic silver.
34. A method for treating a wound in a subject in need thereof, the method comprising
administering to the wound a wound insert of any one of claims 1-33.
35. The method of claim 34, wherein the wound is a tunneling wound, a dermal wound, a diabetic wound, an acute wound, a chronic wound, or a combination of any two or more thereof.
36. The method of claim 34 or claim 35, wherein the wound is a tunneling wound.
37. The method of any one of claims 34-36, wherein the wound insert is administered directly to the wound.
38. The method of any one of claims 34-37, further comprising providing negative pressure to the wound.
39. The method of any one of claims 34-38, further comprising removing the wound insert, wherein the wound insert is removed by pulling the suture thread away from the wound.
40. A method of manufacturing a wound insert comprising:
fabricating an outer layer of the wound insert from a first slurry comprising one or more biopolymers, wherein the outer layer is in a shape having a hollow center;
photo-crosslinking or reagent-crosslinking the outer layer to obtain one or more
photocrosslinked and reagent-crosslinked biopolymers;
drying the outer layer of the wound insert;
depositing a second slurry into the hollow center of the outer layer to form an inner core of the wound insert; and
removing residual moisture from the inner core;
wherein:
the shape of the outer layer comprises a cylinder, a sphere, a cube, a cuboid, a hexagonal prism, a cone, a square-based pyramid, triangular-based pyramid, or a triangular prism;
the second slurry comprises a biopolymer;
the outer layer exhibits a modulus of elasticity from about 0.5 MPa to about 5.0 MPa; and
the inner core exhibits a lower modulus of elasticity than the outer layer.
41. The method of claim 40, wherein the first slurry has a pH from about 3 to 7.
42. The method of claim 40 or claim 41, wherein the first slurry has a pH from about 4.5 to about 5.5.
43. The method of any one of claims 40-42, wherein the first slurry comprises one or more biopolymers comprising a collagen, an oxidized cellulose, an oxidized regenerated cellulose (ORC), a polysaccharide, a chitosan, a gelatin, hyaluronic acid, or a
combination of any two or more thereof.
44. The method of any one of claims 40-43, wherein the first slurry further comprises at least one plasticizer.
45. The method of any one of claims 40-44, wherein the first slurry comprises about 2 wt.% to about 30 wt.% of at least one plasticizer.
46. The method of claim 44 or claim 45, wherein the at least one plasticizer comprises an acetylated monoglyceride, an alkyl citrate, methyl ricinoleate, glycerol, or a combination of any two or more thereof.
47. The method of any one of claims 40-46, wherein the fabricating comprises extruding the first slurry to fabricate the outer layer.
48. The method of any one of claims 40-47, further comprising treating the outer layer with a weak basic gas.
49. The method of claim 48, wherein the weak basic gas is ammonia.
50. The method of any one of claims 40-49, wherein the biopolymer of the second slurry comprises a collagen, an oxidized cellulose, an oxidized regenerated cellulose (ORC), a polysaccharide, a chitosan, a gelatin, hyaluronic acid, or a combination of any two or more thereof.
51. The method of any one of claims 40-50, wherein the second slurry comprises one or more of collagen and chitosan along with ORC, wherein a weight ratio of the one or more of collagen and chitosan to ORC is about 60:40 to about 40:60.
52. The method of any one of claims 40-51, wherein the second slurry comprises about 10 wt.% to about 100 wt.% of the biopolymer.
53. The method of any one of claims 40-52, wherein the second slurry comprises 0.001 wt.% to about 5 wt.% of an antimicrobial agent.
54. The method of any one of claims 40-53, wherein the second slurry further comprises 0.001 wt.% to about 5 wt.% of a source for ionic silver.
55. The method of any one claims 40-54, wherein removing residual water from the inner core comprises freeze drying the inner core.
56. A wound insert prepared according to the method of any one of claims 40-55.
57. A kit comprising the wound insert of any one of claims 1-33, and instructions for use.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201962868629P | 2019-06-28 | 2019-06-28 | |
US62/868,629 | 2019-06-28 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2020264132A1 true WO2020264132A1 (en) | 2020-12-30 |
Family
ID=71614965
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US2020/039576 WO2020264132A1 (en) | 2019-06-28 | 2020-06-25 | Wound inserts for treatment of tunneling wounds |
Country Status (1)
Country | Link |
---|---|
WO (1) | WO2020264132A1 (en) |
Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3122479A (en) | 1957-11-14 | 1964-02-25 | David F Smith | Hemostatic surgical dressings |
US4320201A (en) | 1979-10-27 | 1982-03-16 | Firma Carl Freudenberg | Method for making collagen sponge for medical and cosmetic uses |
US4614794A (en) | 1983-10-04 | 1986-09-30 | Johnson & Johnson | Protein/polysaccharide complexes |
US5254105A (en) * | 1988-05-26 | 1993-10-19 | Haaga John R | Sheath for wound closure caused by a medical tubular device |
US20010046518A1 (en) * | 1998-08-14 | 2001-11-29 | Amarpreet S. Sawhney | Methods of using in situ hydration of hydrogel articles for sealing or augmentation of tissue or vessels |
WO2011057131A1 (en) * | 2009-11-09 | 2011-05-12 | Spotlight Technology Partners Llc | Polysaccharide based hydrogels |
US20130123723A1 (en) * | 2011-11-11 | 2013-05-16 | Kci Licensing, Inc. | Reduced-pressure, tunnel-wound dressings, systems, and methods |
WO2018035063A1 (en) * | 2016-08-16 | 2018-02-22 | Kci Usa, Inc. | Collagen/orc dressing encapsulated within a bioresorbable envelope |
-
2020
- 2020-06-25 WO PCT/US2020/039576 patent/WO2020264132A1/en active Application Filing
Patent Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3122479A (en) | 1957-11-14 | 1964-02-25 | David F Smith | Hemostatic surgical dressings |
US4320201A (en) | 1979-10-27 | 1982-03-16 | Firma Carl Freudenberg | Method for making collagen sponge for medical and cosmetic uses |
US4614794A (en) | 1983-10-04 | 1986-09-30 | Johnson & Johnson | Protein/polysaccharide complexes |
US5254105A (en) * | 1988-05-26 | 1993-10-19 | Haaga John R | Sheath for wound closure caused by a medical tubular device |
US20010046518A1 (en) * | 1998-08-14 | 2001-11-29 | Amarpreet S. Sawhney | Methods of using in situ hydration of hydrogel articles for sealing or augmentation of tissue or vessels |
WO2011057131A1 (en) * | 2009-11-09 | 2011-05-12 | Spotlight Technology Partners Llc | Polysaccharide based hydrogels |
US20130123723A1 (en) * | 2011-11-11 | 2013-05-16 | Kci Licensing, Inc. | Reduced-pressure, tunnel-wound dressings, systems, and methods |
WO2018035063A1 (en) * | 2016-08-16 | 2018-02-22 | Kci Usa, Inc. | Collagen/orc dressing encapsulated within a bioresorbable envelope |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US20230390117A1 (en) | Extended wear-time dressing | |
US11717592B2 (en) | Bioresorbable dressing with structural support | |
US20200337904A1 (en) | Dressing including dehydrated placental tissue for wound healing | |
JP2020520749A (en) | Stretchable covering | |
US3988411A (en) | Spinning and shaping poly-(N-acetyl-D-glucosamine) | |
JP2020520740A (en) | Elastically deformable wound dressing | |
US20060127437A1 (en) | Semisolid system and combination semisolid, multiparticulate system for sealing tissues and/or controlling biological fluids | |
EP3703636A1 (en) | Nutrient-enriched dressing | |
US20140163447A1 (en) | Perforated, Layered Wound Treatment Material | |
US11752235B2 (en) | Collagen/ORC dressing encapsulated within a bioresorbable envelope | |
CN109125799A (en) | GelMA hydrogel people takes off the preparation method of the three-dimensional double-deck auxiliary material of cell amnion | |
US20220142820A1 (en) | Antimicrobial dressing, dressing components, and methods | |
US3989535A (en) | Solution of poly(N-acetyl-D-glucosamine) | |
WO2020264132A1 (en) | Wound inserts for treatment of tunneling wounds | |
US20230029576A1 (en) | Means to improve usability of a wound insert for application to deep wounds | |
RU2312658C1 (en) | Film-forming aerosol for wound protection in treatment and method for its using | |
WO1997017044A1 (en) | Membrane for skin removed wound | |
Mashudi et al. | A Novel Dressing for Wound Care Based on Konjac Glucomannan | |
EP3990036B1 (en) | Citric acid coated wound dressing compositions and methods of manufacture | |
US20230079448A1 (en) | Devices and methods for negative pressure therapy | |
WO2021148851A1 (en) | Bio-resorbable wound filler for deep tissue wound closure | |
CN115944790A (en) | Abdominal wall patch and preparation method thereof | |
Verma et al. | Compression Bandage and Wound Care Biomaterial With Nanotechnology | |
CN205434084U (en) | A wrap subsides for skin large tracts of land wound | |
Hess | Hydrocolloids: Healing by Occlusion |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 20740465 Country of ref document: EP Kind code of ref document: A1 |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
122 | Ep: pct application non-entry in european phase |
Ref document number: 20740465 Country of ref document: EP Kind code of ref document: A1 |