CN104548189B - Microballoon and its application in wound hemostasis - Google Patents
Microballoon and its application in wound hemostasis Download PDFInfo
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- CN104548189B CN104548189B CN201510044381.8A CN201510044381A CN104548189B CN 104548189 B CN104548189 B CN 104548189B CN 201510044381 A CN201510044381 A CN 201510044381A CN 104548189 B CN104548189 B CN 104548189B
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- microballoon
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- sodium alginate
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Abstract
A kind of microballoon, is grouped point, contained collagen is more than 0.5w/w% using sodium alginate, carboxymethyl chitosan and collagen to be main.The imbibition multiple of microballoon of the present invention can reach more than 50, can be used for wound hemostasis as dressing.
Description
Technical field
The present invention relates to medical composite, more particularly to a kind of microballoon, with higher pick up, doctor can be suitably used for
Treatment field, such as：Wound hemostasis.
Background technology
Medical dressing in wound healing process, can substitute impaired skin and play temporarily as the covering of wound
The barrier action of when property, it is to avoid or there is provided the environment for being conducive to wound healing for control wound infection.With the aging of population and slow
Property exedens wound increases, and closely related biomaterial is related to the various dressing of the surface of a wound and covering with wound repair, medical
The market value of dressing also becomes more and more important.
Announced in July, 2012 according to Kalorama Information《Wound Care Markets》Report, by
In natural calamity, the wound such as war and contingency is continuously increased, to the hemostasis with blood vessel sealing effectiveness, wound repair material
The world market capacity of material is estimated to grow beyond 15% every year, and product has huge market demand.
Chinese invention patent ZL 200610024198.2 discloses a kind of high, the biodegradable styptic powder of swelling ratio, its
By 1~2g of carboxymethyl cellulose, 1~2g of sodium alginate, 0.8~1.6g of calcium chloride, 250~1000ml of atoleine and 18~
The Main Ingredients and Appearances such as 75ml Tween 80s are prepared from, be it is a kind of with many fold surfaces, can quick water absorption and swelling microballoon, with compared with
Good haemostatic effect.But after irradiated sterilizing, its Water absorption is reduced to
At present, a few class massive haemorrhage bleeding-stopping dressing products of international market are occupied, include trade name Quick-Clot boiling
The Arista dressing of stone dressing, RDH chitosan dressings, CELOX chitosan dressings, Medafor companies based on plant amylum, and
Dressing etc. is mixed, all also in the market development stage, is not definitely dominated the market also, though and above-mentioned a few class dressing have respective excellent
Gesture, but there is also certain defect, can also be in industry by universal accreditation without a kind of dressing.
According to another 2011~2015 Chinese hemostatic material market Long-and Medium-term Development prediction addresses, China was every year because the surface of a wound is big
Bleeding and the number that needs hemostasis is about 9,000,000.Stop blooding by each realized with one bag of hemostatic microsphere come Conservative estimation, every year
The market demand of surface of a wound massive haemorrhage hemostatic material is about 9,000,000 bags.But the such hemostatic microsphere of current China is relatively deficient, tradition
Hemostatic gauze or clinical operation bleeding-stopping dressing it is general to the haemostatic effect of surface of a wound massive haemorrhage.New pattern compress styptic sponge,
Though the haemostatic effects such as haemostatic membrane increase, the complicated surface of a wound is difficult to accurately to find blutpunkte, have impact on it actual hemostatic
Energy.
Chinese invention patent ZL 201010525865.1 discloses a kind of mesopore bioactive glass and chitosan is compound more
Hole hemostatic material and preparation method, by account for whole composite mass percent 1~90% mesopore bioactive glass with
Porous microsphere, mandruka or porous powder that chitosan is composited.
Chinese invention patent application 201210382569.X discloses a kind of preparation method of tapioca microballoon, including will
Tapioca solution and polyglycol solution stirred at 30 DEG C 10 minutes formed water-water (W/W) emulsion, then 15 DEG C~
25 DEG C stand incubation after 3 hours~7 hours, centrifuge.Lower floor's gelatinous solid is washed with deionized after 3 times, uses ethanol
Dehydration by vacuum drying, obtains white or flaxen tapioca microballoon, with good haemostatic effect again.
Chinese invention patent application 201310394378.X discloses a kind of styptic powder of sodium hyaluronate composite biodegradable,
It is made up of medical glass hyaluromic acid, plant amylum, Span80, paraffin oil, absolute ethyl alcohol and ethyl acetate etc., is a kind of
With many fold surfaces, can quick water absorption and swelling microballoon, with preferable haemostatic effect.
Though the report of existing massive haemorrhage hemostatic microsphere, can form the then actually rare for number of large-scale production, such as：Mountain
Water absorption >=20 for the compound micropore polysaccharide styptic powder that Dong Saikesaisi medicine companies Science and Technology Ltd. provides, still need to be carried
It is high.The country has been sold at present imported from America Arista hemostatic microspheres (every bag needs 2,000 yuan of RMB, and Water absorption >=10)
CELOX hemostatic gauzes with Britain import are expensive, and only the hospital in down towns such as Beijing, Shanghai and Guangzhou sells,
Do not popularize very much in market.
The content of the invention
It is an object of the present invention to provide a kind of microballoon, pick up, especially irradiated (Co 60) are further improved
After sterilizing, remain to keep higher pick up characteristic.
It is another object of the present invention to provide a microballoon, it is provided simultaneously with good anti-blocking properties and promotes wound to be cured
The characteristic of conjunction, be a kind of biocompatibility it is good, can quickly water absorption and swelling and the microballoon of biodegradable absorption.
It is yet a further object of the present invention to provide a kind of microballoon, as dressing, for wound hemostasis.
A further object of the present invention is to provide a kind of preparation method of microballoon.
A kind of microballoon that the present invention is provided, is grouped point using sodium alginate, carboxymethyl chitosan and collagen to be main.
Another microballoon that the present invention is provided, using sodium alginate, carboxymethyl chitosan and collagen to be mainly grouped
Point, in addition to solvent and surfactant.
The solvent used in various microballoons that the present invention is provided is such as：But be not limited only to atoleine, soybean oil, ethyl acetate,
Castor oil, isopropyl myristate and isopropyl palmitate etc., its can individually or mixing be applied to the present invention.
The surfactant used in various microballoons that the present invention is provided is such as：But it is not limited only to Tween 80 (Tween 80), tells
60 (Tween 60) of temperature, polysorbas20 (Tween 20), lecithin and the stearic acid esters of polyoxyethylene 20 etc., its can individually or
Mixing is applied to the present invention.
The collagen contained by various microballoons that the present invention is provided is more than 0.5w/w%, such as：But be not limited only to 1w/w%~
4w/w%.
Sodium alginate, carboxymethyl chitosan and the collagen used in various microballoons that the present invention is provided be by weight ratio
20~60: 10~20: 1.
Various microballoons its particle diameter that the present invention is provided is less than 300 μm, and integrated distribution is in 10 μm~100 μm of scope, such as：
Microballoon less than 100 μm accounts for more than 70%, more than 80%, more than 90% or more.
The present invention is various to produce microballoon, and its imbibition multiple, can be directly as dressing up to more than 50, or dressing is made for creating
Wound hemostasis.
The various microballoons that the present invention is provided, are comprised the following steps：
Matrix solution containing sodium alginate, carboxymethyl chitosan and collagen is added to containing emulsifying agent and solvent
The second solution in, and accompany by quick stirring, be additionally added 2w/w%~4w/w% calcium chloride solution, produce microballoon.
Obtained microballoon, soaks also in ethanol, and stands, to obtain precipitation.
The present invention is various to produce the sodium alginate contained in micro-sphere method, matrix solution, carboxymethyl chitosan and collagen egg
It is 20~60: 10~20: 1 by weight ratio in vain.
The present invention is various to produce micro-sphere method, and the volume ratio of emulsifying agent and solvent is 10~15: 1.
The beneficial effect that technical solution of the present invention is realized：
The microballoon that the present invention is provided, is grouped point, raising using sodium alginate, carboxymethyl chitosan and collagen to be main
The degree of cross linking of microballoon, significantly increases the imbibition multiple of microballoon.Especially after microballoon is in irradiation sterilization, it still has 50 times
Imbibition multiple above, can be used for wound hemostasis as dressing.
The microballoon that the present invention is provided is higher to hematoblastic adhesion rate, 50% is approached in 0.5min, and continue to
2.5min, it can promote hematoblastic in the hemostasis first stage stick as hemostatic material.
Brief description of the drawings
Fig. 1 is the electron microscope of microballoon of the present invention.
Embodiment
Technical scheme is described in detail below in conjunction with accompanying drawing.Skill of the embodiment of the present invention only to illustrate the present invention
Art scheme and it is unrestricted, although the present invention is described in detail with reference to preferred embodiment, one of ordinary skill in the art
It should be appreciated that can be modified to the technical scheme of invention or equivalent substitution, without departing from the essence of technical solution of the present invention
God and scope, it all should cover in scope of the presently claimed invention.
In following examples of the present invention, the pick up for producing microballoon is determined as follows：
Take 0.2g microballoons to be put into 500 mesh medicines sieve sack, use scales/electronic balance weighing sack, be designated as m1, distillation is slowly added dropwise
Water squeezes out unnecessary moisture untill sample no longer absorbs water, then uses scales/electronic balance weighing sack, is designated as m2, suction is calculated as follows
Water rate Q.
Embodiment 1
1.5g sodium alginates, 0.5g carboxymethyl chitosans and 0.025g collagens are added in 100ml water and dissolved, system
Into matrix solution.
250ml atoleines are mixed with 18.75ml Tween 80s, add matrix solution, and 2w/w% calcium chloride 10ml, and
Quick stirring is accompanied by, microballoon is made to carry out cross-linking reaction.
After end, the ethanol for adding 500ml soaks 2 hours, waits microballoon with after solution layering, removing clear liquid liquid, precipitation is taken out
Filter is inserted in vacuum drying chamber, 60 DEG C are dried with further removing after redundant solution.Dried microballoon is under Electronic Speculum
Form is as shown in figure 1, through laser diffractometry Analyzer testing result, the particle diameter distribution of more than 90% microballoon is in 10 μm~100 μm
Between.
Embodiment 2
1.0g sodium alginates, 0.5g carboxymethyl chitosans and 0.025g collagens are added in 100ml water and dissolved, system
Into matrix solution.
250ml soybean oils are mixed with 18.75ml polysorbate60s, add matrix solution, and 4w/w% calcium chloride 10ml, and companion
Quickly to stir, microballoon is made to carry out cross-linking reaction.
After end, the ethanol for adding 500ml soaks 2 hours, waits microballoon with after solution layering, removing clear liquid liquid, precipitation is taken out
Filter is inserted in vacuum drying chamber, 60 DEG C are dried with further removing after redundant solution.Dried microballoon is through laser diffraction
Method Analyzer testing result, the particle diameter distribution of more than 90% microballoon is between 10 μm~100 μm.
Embodiment 3
0.5g sodium alginates, 0.5g carboxymethyl chitosans and 0.025g collagens are added in 100ml water and dissolved, system
Into matrix solution.
250ml castor oil is mixed with 18.75ml lecithin, adds matrix solution, and 2w/w% calcium chloride 10ml, and companion
Quickly to stir, microballoon is made to carry out cross-linking reaction.
After end, the ethanol for adding 500ml soaks 2 hours, waits microballoon with after solution layering, removing clear liquid liquid, precipitation is taken out
Filter is inserted in vacuum drying chamber, 60 DEG C are dried with further removing after redundant solution.Dried microballoon is through laser diffraction
Method Analyzer testing result, the particle diameter distribution of more than 90% microballoon is between 10 μm~100 μm.
Embodiment 4
1.5g sodium alginates, 0.25g carboxymethyl chitosans and 0.025g collagens are added in 100ml water and dissolved,
Matrix solution is made.
250ml castor oil is mixed with 25ml lecithin, adds matrix solution, and 2w/w% calcium chloride 10ml, and accompany by
Quick stirring, microballoon is made to carry out cross-linking reaction.
After end, the ethanol for adding 500ml soaks 2 hours, waits microballoon with after solution layering, removing clear liquid liquid, precipitation is taken out
Filter is inserted in vacuum drying chamber, 60 DEG C are dried with further removing after redundant solution.Dried microballoon is through laser diffraction
Method Analyzer testing result, the particle diameter distribution of more than 90% microballoon is between 10 μm~100 μm.
Embodiment 5
1g sodium alginates, 0.375g carboxymethyl chitosans and 0.025g collagens are added in 100ml water and dissolved, system
Into matrix solution.
250ml isopropyl palmitates are mixed with the stearate of 25ml polyoxyethylene 20, add matrix solution, and 2w/
W% calcium chloride 10ml, and quick stirring is accompanied by, microballoon is made to carry out cross-linking reaction.
After end, the ethanol for adding 500ml soaks 2 hours, waits microballoon with after solution layering, removing clear liquid liquid, precipitation is taken out
Filter is inserted in vacuum drying chamber, 60 DEG C are dried with further removing after redundant solution.Dried microballoon is through laser diffraction
Method Analyzer testing result, the particle diameter distribution of more than 90% microballoon is between 10 μm~100 μm.
Embodiment 6
1g sodium alginates and 1g carboxymethyl chitosans are added in 100ml water and dissolved, aqueous phase solution is made.
250ml atoleines are mixed to prepare oil-phase solution with 18ml Tween80, add aqueous phase solution, and 3.2w/v%
Calcium chloride 10ml, and quick stirring is accompanied by, microballoon is made to carry out cross-linking reaction.
The microballoon for investigating embodiment 1 and embodiment 6 carries out pick up, as a result as shown in table 1.
Table 1
It can be seen that, dramatically increased using the water absorption rate of microballoon made from collagen, for the water absorption rate after 60Coradiation also
It is significantly improved, dressing can be used as, it is adaptable to wound hemostasis.
Embodiment 7
Under physiological conditions, there is blood platelet the function of being attached to foreign matter surface to claim platelet adhesion reaction function.In blood vessel because of wound
When wound is lost blood, hematoblastic hemostasis is divided into two sections, and the first stage is mainly after wound generation, and blood platelet attaches to rapidly wound
Injury, and build up agglomerating, form relatively soft hemostasis and fasten；Second stage is chiefly to facilitate blood clotting and forms solid hemostasis and fastens.
The present embodiment be made microballoon as hemostatic material can promote hemostasis the first stage in it is hematoblastic stick, the results are shown in Table 2.
Table 2
From table 2, the microballoon of the present embodiment is more than reference substance to hematoblastic adherence rate.Approached in 0.5min
50%, and continue to 2.5min.Illustrate that the haemostatic effect of the microballoon of the present embodiment is substantially better than reference substance, also reflect this implementation
Example microballoon has the good degree of cross linking.
Claims (8)
1. a kind of microballoon, it is characterised in that raw material is mainly made up of sodium alginate, carboxymethyl chitosan and collagen, alginic acid
Sodium, carboxymethyl chitosan and collagen are 20-60 by weight ratio:10—20:1；The microspherulite diameter is less than 300 μm；Institute
The imbibition multiple after the irradiated sterilizing of microballoon is stated up to more than 50, and microballoon is higher to hematoblastic adhesion rate, in 0.5min
50% is approached, and continues to 2.5min；The preparation method of the microballoon comprises the following steps：Sodium alginate, carboxylic will be contained
Methyl chitosan and collagen matrices solution are added in the second solution containing emulsifying agent and solvent, and are accompanied by and quickly stirred
Mix, be additionally added 2w/w% -4w/w% calcium chloride solution, produce microballoon.
2. microballoon according to claim 1, it is characterised in that the emulsifying agent selected from Tween 80, polysorbate60, polysorbas20,
One of lecithin and the stearic acid esters of polyoxyethylene 20 are planted or several.
3. microballoon according to claim 1, it is characterised in that particle diameter distribution is accounted in the microballoon of 10 μm -100 μ ms
To more than 70%.
4. a kind of microballoon, it is characterised in that the preparation method of the microballoon comprises the following steps：
Second containing emulsifying agent and solvent will be added to containing sodium alginate, carboxymethyl chitosan and collagen matrices solution
In solution, and quick stirring is accompanied by, be additionally added 2w/w% -4w/w% calcium chloride solution, produce microballoon, sodium alginate, carboxylic first
Base enclosure glycan and collagen are 20-60 by weight ratio:10—20:1；The microballoon is higher to hematoblastic adhesion rate,
50% is approached during 0.5min, and continues to 2.5min.
5. microballoon according to claim 4, it is characterised in that described solvent is selected from atoleine, soybean oil, acetic acid
Ethyl ester, castor oil, the one or more of isopropyl myristate and isopropyl palmitate.
6. microballoon according to claim 4, it is characterised in that the emulsifying agent selected from Tween 80, polysorbate60, polysorbas20,
One of lecithin and the stearic acid esters of polyoxyethylene 20 are planted or several.
7. microballoon according to claim 4, it is characterised in that the volume ratio of emulsifying agent and solvent is 10-15:1.
8. the microballoon according to one of claim 1-7 is used for the dressing of wound hemostasis.
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| CN105963766A (en) * | 2016-07-06 | 2016-09-28 | 浙江理工大学 | Absorbable antibacterial hemostatic microsphere, preparation method and application thereof |
| CN106336517A (en) * | 2016-09-09 | 2017-01-18 | 温州生物材料与工程研究所 | Physical crosslinking natural polysaccharide microsphere, preparation method and use |
| CN106540308A (en) * | 2016-11-29 | 2017-03-29 | 温州生物材料与工程研究所 | A kind of degradable multiporous microsphere and Preparation method and use |
| CN107029280B (en) * | 2017-04-07 | 2019-04-19 | 广东海洋大学 | A kind of preparation method of chitin-alginic acid salt soft capsule grain hemostatic material |
| CN108355164B (en) * | 2018-03-24 | 2021-06-11 | 浙江理工大学 | Absorbable platelet-like biomass material and application thereof |
| CN113599281A (en) * | 2021-08-10 | 2021-11-05 | 王思远 | Collagen polypeptide carboxymethyl chitosan nano slow-release particle and manufacturing method thereof |
| CN114306717B (en) * | 2021-11-30 | 2022-07-26 | 中国科学院南海海洋研究所 | Marine biomedical material for repairing skin wounds and preparation method and application thereof |
| CN115137710B (en) * | 2022-05-25 | 2024-04-12 | 广东药科大学 | Antibacterial volatile oil gel microsphere, preparation method thereof and microsphere mask comprising antibacterial volatile oil gel microsphere |
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| JP4159682B2 (en) * | 1998-12-22 | 2008-10-01 | 株式会社クラレ | Hemostatic material |
| CN100367933C (en) * | 2006-02-28 | 2008-02-13 | 中国人民解放军第二军医大学 | Biodegradeable hemostasis powder |
| CN102309776A (en) * | 2011-09-05 | 2012-01-11 | 北京博恩康生物科技有限公司 | A kind of powdery absorbable hemostatics and preparation method thereof |
| CN102885710B (en) * | 2012-10-22 | 2014-10-22 | 西安雅芝生物科技有限公司 | Sodium alga acid/chitosan/collagen composite micro-ball with active components and preparation method of composite micro-ball |
| CN103923962A (en) * | 2013-01-10 | 2014-07-16 | 上海其胜生物制剂有限公司 | I type collagen monomer sponge preparation method |
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