TWI597075B - Hydrophilic polyurethane, hydrophilic polyurethane foam and its preparation Wet wound dressing - Google Patents

Description

Hydrophilic polyurethane, hydrophilic polyurethane foam and its preparation Wet wound dressing

The present invention relates to a polyurethane, and more particularly to a hydrophilic polyurethane, a hydrophilic polyurethane foam, and a wet wound dressing thereof.

Due to the increased awareness of health care, wound care after surgery has received much attention. Therefore, various wound dressings that can avoid infection and protect wounds have been developed.

In order to further promote wound healing, it is usually mixed in the dressing substrate or coated on the surface to promote wound healing (for example: alginate, hyaluronic acid or its salt, hypoglycate, etc.), However, blending or coating requires not only an additional processing process, but these additional added active ingredients are prone to wear and loss and require frequent dressing changes (approximately 5 to 7 days), and may also be due to absorption of the active ingredient by the dressing substrate. Reducing the absorption of wound dressing by wound dressing has limited help for wound healing.

Therefore, the first object of the present invention is to provide a hydrophilic polyurethane which can be covered in a wound as a wound dressing and has a wet wound. It moisturizes and promotes wound healing and hydrophilicity that effectively absorbs wound exudate.

Thus, the hydrophilic polyurethane first polyether polyol of the present invention is reacted with a polyisocyanate, followed by a star block polyurethane obtained by reacting with a second polyether polyol and hyaluronic acid, wherein the first A polyether polyol contains at least three terminal hydroxyl groups.

A second object of the present invention is to provide a hydrophilic polyurethane foam obtained by foaming a hydrophilic polyurethane and a foaming component as described above, and the pores of the hydrophilic polyurethane foam are not Continuous closed hole.

A third object of the present invention is to provide a wet wound dressing comprising a sheet-like absorbent layer which is made of a hydrophilic polyurethane or a hydrophilic polyurethane foam as described above.

The effect of the invention is that the star-shaped block polyurethane obtained by reacting polyether polyol, polyisocyanate and hyaluronic acid can produce a wet wound dressing which can effectively promote wound healing and absorb wound exudate.

The details of the present invention will be described below. The star-like structure of the star-shaped block polyurethane allows the polyurethane to have a large specific surface area to enhance the water absorption characteristics of the hydrophilic polyurethane.

Preferably, the hyaluronic acid has a weight average molecular weight ranging from 500,000 to 2,500,000. Hyaluronic acid having a weight average molecular weight higher than 2,500,000 is less favorable for promoting wound healing. In a particular embodiment of the invention, the hyaluronic acid has a weight average molecular weight of 1,000,000.

Preferably, the first polyether polyol, the polyisocyanate The total of the second polyether polyol and the hyaluronic acid is 100 mol%, and the hyaluronic acid content is in the range of 0.001 to 20 mol%. More preferably, the hyaluronic acid is contained in an amount ranging from 0.001 to 10 mol%.

Preferably, the polyisocyanate is an aliphatic polyisocyanate to avoid the risk of toxicity which may be selected from aromatic compounds. More preferably, the aliphatic polyisocyanate is selected from the group consisting of hexamcthylene diisocyanate (HDI), methylene dicyclohexyl diisocyanate (H ₁₂ MDI), isophorone diisocyanate. (isophorone diisocyanate, IPDI) or a combination thereof. In a particular embodiment of the invention, the polyisocyanate is hexamethylene diisocyanate.

Preferably, the first polyether polyol is poly(propylene glycol) triol (PPG triol)

Preferably, the second polyether polyol is polyethylene glycol (PEG).

In a specific embodiment of the present invention, the hydrophilic polyurethane is obtained by reacting poly(propylene glycol) triol with the polyisocyanate to form a star-shaped prepolymer, and then crosslinking with polyethylene glycol and hyaluronic acid. Star-shaped block polyurethane.

Preferably, the polyethylene glycol has a weight average molecular weight ranging from 1,000 to 6,000. If the weight average molecular weight of the polyethylene glycol is less than 1,000, biotoxicity is generated via metabolism; if the weight average molecular weight of the polyethylene glycol is more than 6,000, the operation of the crosslinking reaction may be difficult due to the high viscosity, but if Adding solvent to reduce viscosity for operation may result in dissolution The agent remains on the dressing and poses a risk of cytotoxicity.

The pores of the hydrophilic polyurethane foam are discontinuous closed pores to avoid the risk of new tissue growing into the wound during healing, and reducing the damage that may be caused by the removal.

Preferably, the foaming component comprises a blowing agent, water, a surfactant, a polyamine, and a catalyst. The polyamine is used to increase the mechanical strength of the hydrophilic polyurethane. More preferably, the polyamine is selected from the group consisting of 1,2-ethanediamine, 1,4-butanediamine, 1,6-hexanediamine, and three. Triethylenetetramine (TETA) or polyetheramine. The polyether amine selected from, but not limited to, produced by Huntsman JEFFAMINE ^®. The catalyst is used to catalyze the reaction of excess polyisocyanate with water to produce carbon dioxide. More preferably, the catalyst may be selected from zinc isooctylate, triethylene glycol diamine (TEDA, DABCO), dimethylcyclohexylamine (DMCHA). , dimethylethanolamine (DMEA), triethylamine (TEA), 1,8-dioxinbicyclo[5.4.0]undec-7-ene (DBU) or pentamethyldiethylenetriamine (PMDETA) ).

Preferably, the wet wound dressing of the present invention further comprises a backing, the sheet-like absorbent layer being affixed to the backing for adhering to the skin surrounding the wound. More preferably, in order to maintain the tack of the backing, the wet wound dressing of the present invention further comprises a release paper covering the sheet-like absorbent layer and the backing for tearing prior to use.

1‧‧‧Flake absorption layer

21‧‧‧Backing

22‧‧‧ release paper

Other features and effects of the present invention will be apparent from the following description of the drawings, wherein: Figure 1 is a perspective view illustrating the hydrophilic polyurethane of the present invention or Hydrophilic polyurethane foam; and Figure 2 is a perspective schematic view of the wet wound dressing of the present invention.

Before the present invention is described in detail, it should be noted that in the following description, similar elements are denoted by the same reference numerals.

The invention is further described in the following examples, but it should be understood that these examples are for illustrative purposes only and are not to be construed as limiting.

<Example 1> Star-shaped hydrophilic polyurethane PU1

1 mol of PPG6000 triol (weight average molecular weight of 6,000) was mixed with 3 mol of HDI, and reacted at 80 ° C for 1 hour to obtain a star-shaped prepolymer, and then 1 mol of PEG 1000 (weight average molecular weight of 1,000) and 1.5 mol of PEG 2000 (weight average molecular weight) were added. 2,000) and 0.5 mol of hyaluronic acid (weight average molecular weight: 1,000,000) were subjected to a crosslinking reaction at 80 ° C for 6 hours to obtain a star-shaped hydrophilic polyurethane PU1.

<Example 2> Star-shaped hydrophilic polyurethane PU2

0.5 mol of PPG6000 triol was mixed with 2.5 mol of HDI, and reacted at 80 ° C for 1 hour to obtain a star-shaped prepolymer, and then 0.85 mol of PEG 1000, 0.85 mol of PEG 2000 and 0.1 mol of hyaluronic acid (weight average molecular weight of 1,000,000) were added. The crosslinking reaction was carried out at 80 ° C for 6 hours to obtain a star-shaped hydrophilic polyurethane PU2.

<Application Example 1> Wet wound dressing DR1

Referring to Figure 1, the star-shaped hydrophilic polyurethane PU1 of Example 1 was mixed with 1 mol of HDI and applied to a release film, and added at 120 ° C. After 1 hour of heat, a sheet-like absorbent layer 1 as shown in Fig. 1 was obtained, that is, a wet wound dressing DR1.

<Application Example 2> Wet wound dressing DR2

Referring to Figures 1 and 2, 0.1 mol of sodium bicarbonate (foaming agent), 0.4 mol of water, 0.5 mol of polydimethyloxane-polyoxyalkylene copolymer (surfactant), 0.1 mol of ethylenediamine and 0.1 are used. Mol isooctanoate zinc (catalyst, purchased from Taishengjin Chemical Industry Co., Ltd., Taiwan, model TMG620) was mixed to obtain a foaming component, followed by the star-shaped hydrophilic polyurethane PU2 of Example 2 and the foaming component. The mixture is rapidly stirred and mixed, and a hydrophilic polyurethane foam is obtained after foam molding, and the pores of the hydrophilic polyurethane foam are discontinuous closed pores. The hydrophilic polyurethane foam is cut into a sheet-like absorbent layer 1 of an appropriate size, and fixedly adhered to a viscous backing 21, and a release paper 22 is covered on the sheet-like absorbent layer. On the backing 21, the wet wound dressing DR2 of Application Example 2 was obtained.

<Comparative Application Example 1> Wound Dressing CDR1

The wound dressing CDR1 of Comparative Application Example 1 was a general gauze.

<Comparative Application Example 2> Wound dressing CDR2

The wound dressing CDR 2 of Comparative Example 2 was a soft wound dressing 3662A commercially available from 3M Company, and the material in contact with the wound was a non-woven fabric.

<Comparative Application Example 3> Wet wound dressing CDR3

Water wet gel wound dressing HERADERM ^® wound dressing CDR3 Comparative Example 3, commercially available as AMED company, the material is in contact with the wound 2-hydroxyethyl methacrylate (HEMA).

<Wound healing test>

A. Experimental animals:

The S. D. rats used in the experiments below were male Sprague-Dawley (S.D.) rats (8 weeks old and weighing 200 g). All experimental animals were housed in a separate air-conditioned animal room with light and dark for 12 hours, room temperature maintained at 22 ° C and relative humidity maintained at 42%, and water and feed were adequately supplied. Animals were given at least 2 weeks to adjust to the environment prior to the experiment. The feeding environment, treatment, and all experimental procedures for experimental animals are in accordance with the National Institutes of Health (NIH) Guide for the Care and Use of Laboratory Animals.

B. Sterilization of biofiber dressings:

The wound dressings DR1, DR2 and CDR1 obtained in the above Application Examples 1, 2 and Comparative Application Example 1 were sterilized by gamma ray (dose of 40 kGy), and then subjected to the following experiment. .

C. Formation of skin wounds:

The dosal part of the S.D. rat was shaved and then disinfected with tincture of iodine and 70% alcohol. Thereafter, a skin wound having an area size of about 2 cm × 2 cm and a depth of about 2 to 3 mm was cut out on the left side of the back of the S.D. rat using a surgical knife.

D. Application of dressing:

S.D. rats were randomly divided into 2 experimental groups and 3 control groups (ie, experimental group 1, 2 and control group 1 to 3) (n=3 per group), among which Each group of S.D. rats was formed into a skin wound in accordance with the method described in item C above. Next, the skin wounds of the SD rats of the experimental groups 1 and 2 were respectively administered with the sterilized wet wound dressings DR1 and DR2 prepared according to the above item B, while the SD rats of the control groups 1, 2 and 3 were administered. The skin wounds were applied separately to the sterilized wound dressing CDR1 prepared according to item B above, the wound dressing CDR2 of Comparative Application Example 2, and the wound dressing CDR3 of Comparative Application Example 3. The experiment was carried out for a total of 7 days, and the wound area of each group of S.D. rats was measured at 1, 3, 5, and 7 days after the application of the dressing, and the results are shown in Table 1 below.

It can be seen from the above Table 1 that the skin wound area of the SD rats of the experimental groups 1 and 2 was significantly reduced on the 1st to 7th day after the application of the dressing, wherein the skin wound of the SD rats of the experimental group 2 was On the 7th day after the application of the dressing, it almost completely healed, while in the control group 1 to 3, the skin wounds in the SD rats were significantly slower in area, indicating that the wet wound dressings DR1 and DR2 of the experimental groups 1 and 2 were wound healing. It is more significant than the control group 1~3 gauze or the commercially available dressing wound dressings CDR1~CDR3 help.

In summary, the hydrophilic polyurethane and the hydrophilic polyurethane foam of the present invention are obtained by reacting a polyether polyol, a polyisocyanate and a hyaluronic acid to obtain a star-shaped block polyurethane, which can effectively promote wound healing and can A wet wound dressing that absorbs wound exudate, and the closed pores of the hydrophilic polyurethane foam of the present invention can avoid the damage that may be caused when removed. Further, the raw material of the wet wound dressing of the present invention does not contain a monomer or a crosslinking agent which may be toxic, and thus the object of the present invention can be achieved.

However, the above is only the embodiment of the present invention, and the scope of the invention is not limited thereto, and all the equivalent equivalent changes and modifications according to the scope of the patent application and the patent specification of the present invention are still The scope of the invention is covered.

1‧‧‧Flake absorption layer

21‧‧‧Backing

22‧‧‧ release paper

Claims (8)

a hydrophilic polyurethane which is a star-shaped block polyurethane obtained by reacting a first polyether polyol with a polyisocyanate, followed by reacting with a second polyether polyol and hyaluronic acid, wherein the first polyether polyol Containing at least three terminal hydroxyl groups, the hyaluronic acid has a weight average molecular weight ranging from 500,000 to 2,500,000. The hydrophilic polyurethane according to claim 1, wherein the total of the first polyether polyol, the polyisocyanate, the second polyether polyol, and the hyaluronic acid is 100 mol%, and the hyaluronic acid is The content ranges from 0.001 to 20 mol%. The hydrophilic polyurethane according to claim 1, wherein the polyisocyanate is an aliphatic polyisocyanate. The hydrophilic polyurethane according to claim 1, wherein the first polyether polyol is poly(propylene glycol) triol. The hydrophilic polyurethane according to claim 1, wherein the second polyether polyol is polyethylene glycol. The hydrophilic polyurethane according to claim 5, wherein the polyethylene glycol has a weight average molecular weight ranging from 1,000 to 6,000. A hydrophilic polyurethane foam obtained by foaming a hydrophilic polyurethane and a foaming component according to claim 1, wherein the pores of the hydrophilic polyurethane foam are discontinuous closed pores, wherein The foaming component includes a blowing agent, water, a surfactant, a polyamine, and a catalyst. A wet wound dressing comprising a sheet-like absorbent layer, the sheet-like absorbent layer being made of a hydrophilic polyurethane as claimed in claim 1 or as claimed in claim 7 The hydrophilic polyurethane foam.