TW201726186A - Wet wound dressing - Google Patents

Abstract

A wet wound dressing which is formed by hydrophilic polyurethane foams is provided. The hydrophilic polyurethane foams are formed by the hydrophilic polyurethane and foaming composition. The hydrophilic polyurethane is made of a first polyether polyol reacting with polyisocyanate, and then turns to a star-shaped hydrophilic polyurethane by reacting with a second polyether polyol. The first polyether polyol contains at least three of terminal hydroxyl groups. The hydrophilic polyurethane foams are non-continuous closed holes. Since the wet wound dressing has superior permeability, absorbability and preventing adhesions, it could improve wound healing by prolonging the interval of dressing change.

Description

Wet wound dressing

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

Wound dressings are ideal wound dressings that have the characteristics of maintaining a proper moist environment, avoiding interference with growth, preventing scarring, preventing wound sticking and infiltration. In particular, when the wound is kept in a proper moist environment, the fibroblast can be rapidly moved to accelerate microvascular production, and the wound can be accelerated by promoting the growth of the cells by a large amount of collagen and growth factors contained in the tissue fluid exuded from the wound. Healing. In addition, since the ideal wound dressing does not need to be replaced frequently, the wound can be kept in a closed, moist, and breathable environment, and can be infected by foreign bacteria, and can achieve the effect of self-debridement.

However, in the conventional way of natural healing, using gauze or cotton pad, it is easy to dry the wound surface due to contact with air, so that the fibroblast can not move and reduce the amount of exudation of the tissue fluid, which not only delays wound healing, but also easily causes scarring. Moreover, the wound dressing such as gauze often tears the healed tissue together when it is replaced, which is very disadvantageous for the recovery of the wound. In order to keep the wound in a humid environment and avoid the adhesion of the wound, a wound dressing such as artificial skin and foam is developed. However, the artificial skin is liable to cause infiltration by soaking the wound in the tissue fluid due to poor water absorption. On the other hand, although the foam has a good water absorption property and can be maintained in a moist environment, there is a problem that the wound is easily adhered to because of the large pore diameter. Therefore, none of the above dressings can have the characteristics of an ideal wound dressing and must be replaced frequently, thereby increasing the risk of the wound being infected by bacteria or viruses and failing to accelerate wound healing.

In view of the above-mentioned problems of the prior art, it is an object of the present invention to provide a wet wound dressing to solve the problem that the dressing of the prior art cannot combine the breathability, the water absorption, the moisture retention, and the prevention of the wound adhesion. The problem of dressing must be changed frequently.

According to an aspect of the present invention, a wet wound dressing comprising a hydrophilic polyurethane foam formed by foaming a hydrophilic polyurethane and a foaming component is proposed. Wherein the hydrophilic polyurethane is reacted with the first polyether polyol and the polyisocyanate, and then reacted with the second polyether polyol to form a star polyurethane, wherein the first polyether polyol contains at least three terminal hydroxyl groups. . Further, the pores of the hydrophilic polyurethane foam are discontinuous closed pores.

Further, according to another aspect of the present invention, there is provided a hydrophilic polyurethane which is obtained by reacting a first polyether polyol with a polyisocyanate, followed by reaction with a second polyether polyol and hyaluronic acid. A block polyurethane wherein the first polyether polyol contains at least three terminal hydroxyl groups.

Preferably, the polyisocyanate can be an aliphatic polyisocyanate.

Preferably, the foaming component may comprise a blowing agent, water, a surfactant, a polyamine, and a catalyst.

Preferably, the hyaluronic acid has a weight average molecular weight ranging from 500,000 to 2,500,000.

Preferably, the content of hyaluronic acid may range from 0.001 to 20 mol% of the total amount of the first polyether polyol, the polyisocyanate, the second polyether polyol, and the hyaluronic acid, and more preferably, the hyaluronic acid The content range may be 0.001 to 10% of the total amount.

Preferably, the first polyether polyol may be a polypropylene glycol triol (PPG triol).

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

Preferably, the polyethylene glycol has a weight average molecular weight ranging from 1,000 to 6,000.

Preferably, the polyisocyanate is present in an amount ranging from 20 to 70 mol% of the hydrophilic polyurethane.

Preferably, the content of the first polyether polyol and the second polyether polyol in the hydrophilic polyurethane foam may range from 20 to 70 mol% of the hydrophilic polyurethane.

Preferably, the hydrophilic polyurethane foam may comprise a contact layer and an absorbing layer, and the contact layer and the absorbing layer are integrally formed, wherein the contact layer may have a plurality of first holes, and the absorbing layer may have more than a plurality of first a plurality of second holes in the hole.

Preferably, the wet wound dressing of the present invention may further comprise a gas permeable layer formed of a hydrophilic polyurethane on one side of the absorbent layer, the first polyether polyol and the second polyether polyol in the gas permeable layer. The content may range from 20 to 70 mol% of the hydrophilic polyurethane.

Preferably, the contact layer may be formed by scraping a surface of the hydrophilic polyurethane foam while forming a hydrophilic polyurethane foam, followed by applying a predetermined pressure.

Preferably, the predetermined pressure is in the range of 100 to 300 g/cm ² .

In summary, the wet wound dressing of the present invention has one or more of the following advantages:

(1) Gas permeability: Since the hydrophilic polyurethane in the wet wound dressing of the present invention has both a hydrophilic end and a hydrophobic end, the molecules are repelled and do not cross-link with each other, so It has a small gap to achieve a breathable effect.

(2) Water Absorption: The wet wound dressing of the present invention has a star-shaped structure having a large specific surface area by star-shaped polyurethane to enhance the water absorption of the wound dressing, thereby absorbing too much tissue fluid and avoiding cell infiltration.

(3) Preventing wound adhesion: The wet wound dressing of the present invention prevents the proliferating cells from entering the contact layer by discontinuously closing the pores, and has anti-protein and cell paste by the polyethylene glycol in the material. The attached features are more resistant to the adhesion of the wound.

The technical features, contents, and advantages of the present invention, as well as the advantages thereof, can be understood by the present inventors, and the present invention will be described in detail with reference to the accompanying drawings. The subject matter is only for the purpose of illustration and description, and is not necessarily the true proportion and precise configuration after the implementation of the present invention. Therefore, the scope and configuration relationship of the attached drawings should not be interpreted or limited. First described.

The embodiments of the wet wound dressing according to the present invention will be described below with reference to the related drawings. For ease of understanding, the same elements in the following embodiments are denoted by the same reference numerals.

Please refer to FIG. 1 and FIG. 2 together. FIG. 1 and FIG. 2 are schematic diagrams and operation diagrams of the first embodiment of the wet wound dressing of the present invention. In the first embodiment of the present invention, the wet wound dressing is formed of the hydrophilic polyurethane foam 100, but is not limited thereto, and may be directly formed of hydrophilic polyurethane without foaming. The hydrophilic polyurethane is a first polyether polyol comprising at least three terminal hydroxyl groups, preferably poly(propylene glycol) triol is reacted with a polyisocyanate to extend to form a star prepolymer, followed by star prepolymerization. And a second polyether polyol, which is preferably a star-shaped block polyurethane obtained by crosslinking a polydiethanol and a hyaluronic acid.

Among them, the polyisocyanate is preferably an aliphatic polyisocyanate to avoid a risk of toxicity which may be selected from an aromatic compound, and more preferably, the aliphatic polyisocyanate may be selected from hexamethylene diisocyanate (hexamethylene diisocyanate, HDI), methylene dicyclohexyl diisocyanate (H ₁₂ MDI), isophorone diisocyanate (IPDI) or a combination thereof. Further, the weight average molecular weight of the polydiethanol is preferably in the range of 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 a solvent to lower the viscosity allows the solvent to remain on the dressing and pose a risk of cytotoxicity. Further, the weight average molecular weight of hyaluronic acid is preferably in the range of 500,000 to 2,500,000. If the weight average molecular weight of hyaluronic acid is more than 2,500,000, it is not conducive to wound healing.

Further, the hydrophilic polyurethane and the foaming component are subjected to a foaming reaction to form a hydrophilic polyurethane foam 100. Wherein, the foaming component may comprise a blowing agent, water, a surfactant, a polyamine and a catalyst. Wherein, the polyamine is used to increase the mechanical strength of the hydrophilic polyurethane, and more preferably, the polyamine is selected from the group consisting of 1,2-ethylenediamine, 1,4-butanediamine, 1,6-hexanediamine, and three Triethylenetetramine (TETA) or polyetheramine. Polyetheramine 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 the group consisting of zinc isooctanoate, triethylene glycol diamine (TEDA, DABCO), dimethylcyclohexylamine (DMCHA), Methylethanolamine (DMEA), triethylamine (TEA), 1,8-dioxabicyclo[5.4.0]undec-7-ene (DBU) or pentamethyldiethylenetriamine (PMDETA).

It is worth mentioning that the pores of the hydrophilic polyurethane foam 100 are produced by reacting an excess of polyisocyanate with water to produce carbon dioxide (CO ₂ ), and foaming reaction with a foaming agent to make the hydrophilic polyurethane self-contained. Formed by foaming. The content of the polyisocyanate may range from 20 to 70 mol%, preferably from 40 to 50 mol%, of the hydrophilic polyurethane. Therefore, in the hydrophilic polyurethane foam 100, discontinuous closed pores can be formed so that the respective pores are independent of each other.

Hereinafter, the wet wound dressing of the present invention will be described in more detail with reference to the following Synthesis Examples and Application Examples, and the following application examples and comparative examples are subjected to a wound healing test.

[Synthesis 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 prepolymer, and then 1 mol of PEG 1000 (weight average molecular weight of 1,000), 1.5 mol was added. PEG2000 (weight average molecular weight: 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.

[Synthesis Example 2] Star-shaped hydrophilic polyurethane PU2

Mix 0.5 mol of PPG6000 triol with 2.5 mol of HDI and react at 80 ° C for 1 hour to obtain a star prepolymer, then add 0.85 mol of PEG 1000, 0.85 mol of PEG2000 and 0.1 mol of hyaluronic acid (weight average molecular weight of 1,000,000) The crosslinking reaction was carried out at 80 ° C for 6 hours to obtain a star-shaped hydrophilic polyurethane PU 2 .

[Application Example 1] Wet wound dressing DR1

The star-shaped hydrophilic polyurethane PU1 of Synthesis Example 1 was mixed with 1 mol of HDI, and then applied onto a release film, and heated at 120 ° C for 1 hour to obtain a wet wound dressing DR1 of the present invention.

[Application Example 2] Wet wound dressing DR2

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 mol of zinc isooctylate (catalyst, It was purchased from Taiwan Tin Sangjin Chemical Industry Co., Ltd., model TMG620) to obtain a foaming component, and then the star-shaped hydrophilic polyurethane PU2 of Synthesis Example 2 was rapidly stirred and mixed with the foaming component to form a foamed molding. Thereafter, a hydrophilic polyurethane foam 100 is obtained, and the pores of the foam 100 are discontinuous closed pores. Next, referring to Fig. 2, the hydrophilic polyurethane foam 100 is cut into an appropriate size, and fixed to the viscous backing 300, and the release paper 301 is covered with the hydrophilic polyurethane foam 100 and The backing 300 was applied to obtain the wet wound dressing DR2 of Application Example 2.

[Comparative Example 1] Wound dressing CDR1

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

[Comparative Example 2] Wound dressing CDR2

The wound dressing CRD2 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 Example 3] Wet wound dressing CDR3

The wet wound dressing CDR3 of Comparative Example 3 was a commercially available water gel wound dressing HERADERA ^® from AMED, and the material in contact with the wound was 2-hydroxyethyl methyl methacrylate (HEMA).

[Wound healing test]

A. Experimental animals

Male SD rats (Sprague-Dawley rats, SD rats) were used in the following experiment (8 weeks old, weighing about 200 g. All experimental animals were kept in the light cycle for 12 hours for light and dark, and 22 °C for room temperature, respectively. The relative humidity is maintained in 42% of the independent air-conditioned animal room, and the water and feed are fully supplied. Before the experiment, the animals are given at least 2 weeks to adapt to the environment. The breeding environment, treatment and all experimental procedures of the experimental animals are in line with national health. Guide for the Care and Use of Laboratory Animals by the National Institutes of Health (NIH).

B. Sterilization of biofiber dressings:

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

C. Formation of skin wounds:

The dorsal part of the SD rat was shaved, followed by disinfected with tincture of iodine and 70% alcohol, and then a surgical knife was used for the SD rat. The left side of the back is cut out to have a skin size of about 2 cm x 2 cm and a depth of about 2 to 3 mm.

D. Application of dressings:

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

Table 1

As shown in Table 1, the skin wound area of the SD rats of the experimental groups 1 and 2 was significantly reduced from the first day to the seventh day after the application of the dressing, wherein the skin wound of the SD rats of the experimental group 2 was applied. On the 7th day after the dressing, the skin was nearly completely healed, while the skin wound area of the SD rats of the control group 1 to 3 was significantly slower, showing the wet wound dressings DR1 and DR2 of the experimental groups 1 and 2 and the control group 1~ The wound dressings of CDR1 to CDR3 of 3 have significantly better wound healing effects.

According to the first embodiment of the present invention, the wet wound dressing of the present invention can enhance the water absorption of the wound dressing by the star-shaped block polyurethane having a large specific surface area, and thus can absorb excessive tissue fluid to avoid cell infiltration. Moreover, by means of discontinuous closed pores and polyethylene glycol having anti-protein and cell attachment properties, the proliferating cells can not enter the wound dressing, thereby preventing the wound from sticking. In addition, the wet wound dressing of the present invention is biosafety since it does not contain monomers or crosslinkers which may be toxic.

Please refer to FIG. 3 to FIG. 6 together. FIG. 3 is a cross-sectional view showing a second embodiment of the wet wound dressing of the present invention, and FIG. 4 to FIG. 6 are the drawings shown in FIG. A cross-sectional view of the stage of the second embodiment. In a second embodiment of the invention, the wet wound dressing comprises a hydrophilic polyurethane foam 100 and a gas permeable layer 200. The hydrophilic polyurethane foam 100 further includes a contact layer 110 and an absorbing layer 120, and the contact layer 110 and the absorbing layer 120 are integrally formed. As shown in FIG. 3, the contact layer 110 has a plurality of first holes 111, and one side thereof is in contact with the wound W. The absorbing layer 120 is located on the other side of the contact layer 110 and has a plurality of second holes 121 larger than the plurality of first holes 111. The gas permeable layer 200 is formed of a hydrophilic polyurethane and is positioned on the absorbent layer 120.

In detail, as shown in Fig. 4, 1 mol of the first polyether polyol was mixed with 3 mol of polyisocyanate, and reacted at 70 ° C for 2 hours to obtain a prepolymer, and then 3 mol of the second polyether polyol was further added. The reaction was carried out at 40 ° C for 0.1 hour to obtain a hydrophilic polyurethane, and the hydrophilic polyurethane was made into a gas permeable layer 200, for example, a polyurethane film, but is not limited thereto. The content of the first polyether polyol and the second polyether polyol in the gas permeable layer 200 may range from 20 to 70 mol%, preferably 40 to 50 mol%, of the hydrophilic polyurethane to form a hydrophilic end and a hydrophobic portion. The gas permeable layer 200 at the end, by mutually repelling the hydrophilic end and the hydrophobic end, can produce pores which only allow gas to pass through, and has good gas permeability. Moreover, the size of the pores can be smaller than that of the water molecules, so that the water molecules cannot enter the gas permeable layer 200, and the effect of waterproofing and inhibiting the growth of microorganisms can be achieved to avoid exogenous infection.

Next, as shown in Fig. 5, 1 mol of the first polyether polyol was mixed with 3 mol of polyisocyanate, and reacted at 70 ° C for 2 hours to obtain a star-shaped prepolymer, followed by the addition of 3 mol of the second polyether polyol, and The reaction was carried out at 40 ° C for 0.1 hour to obtain a star-shaped hydrophilic polyurethane, and the above-mentioned 4 mol of the star-shaped hydrophilic polyurethane and the foaming component were rapidly stirred and mixed, and then coated on the gas permeable layer 200 to foam the hydrophilic polyurethane. The body 100 is integrally formed with the gas permeable layer 200. Wherein, the pore of the hydrophilic polyurethane foam 100 is a discontinuous closed pore, and the content of the first polyether polyol and the second polyether polyol is 20 to 70 mol% of the hydrophilic polyurethane. It is preferably 40 to 50 mol%.

Further, as shown in Fig. 6, when the hydrophilic polyurethane foam 100 is formed (before the completion of the foaming reaction), the surface of the hydrophilic polyurethane foam 100 is, for example, subjected to a scraping operation, but is not limited thereto. And applying a pressure of 100 to 300 g/cm ² , preferably 120 to 250 g/cm ² , to compress the bubbles generated when the surface of the hydrophilic polyurethane foam 100 is subjected to a foaming reaction, thereby A contact layer 110 having a first hole 111 having a small aperture is formed on the surface of the foam 100, and the first hole 111 is preferably smaller than the size of the cell, for example, the diameter may be 40 to 140 μm, preferably 40. ~60 μm, and the absorbing layer 120 is formed between the contact layer 110 and the gas permeable layer 200, and has a second hole 121 larger than the first hole 111, and has a diameter of 100 to 1000 μm, preferably 400 to 800. Mm. The thickness of the contact layer 110 may be 0.1 to 5%, preferably 0.1 to 1%, of the entire thickness of the hydrophilic polyurethane foam 100.

It is worth mentioning that the contact layer 110 can prevent the proliferating cells in the wound W from entering the contact layer 110 by using a discontinuous closed pore smaller than the cell size and polyethylene glycol having anti-protein and cell attachment properties. Achieve the effect of preventing the wound from sticking. In addition, the second hole 121 of the absorbing layer 120 can absorb a large amount of tissue fluid while maintaining the wound in a proper moist environment without causing wound infiltration, thereby accelerating the movement of the fibroblast to promote angiogenesis and increase decomposition of dead tissue. And the speed of fibrin. Further, the second pore 121 absorbs the tissue fluid and then expands and deforms to adhere to the wound W and the skin S, thereby suppressing the contraction of the fibroblast to the center of the wound W to prevent the occurrence of scars.

In summary, the wet wound dressing of the present invention can have good gas permeability by the property of containing both a hydrophilic end and a hydrophobic end in the material, and the star-shaped polyurethane has good water absorption, can avoid wound infiltration, and thus The wound can be kept in a proper moist environment. In addition, the contact layer can utilize the characteristics of polyethylene glycol and the discontinuous closed pores smaller than the cell size to prevent the wound from sticking. Thereby, the wet wound dressing of the present invention can generally be used continuously for 7 to 14 days without interfering with autologous debridement to accelerate wound healing.

The above is intended to be illustrative only and not limiting. Any equivalent modifications or alterations to the spirit and scope of the invention are intended to be included in the scope of the appended claims.

100‧‧‧Hydrophilic polyurethane foam
110‧‧‧Contact layer
111‧‧‧First hole
120‧‧‧absorbing layer
121‧‧‧Second hole
200‧‧‧ breathable layer
300‧‧‧Backing
301‧‧‧ release paper
S‧‧‧ skin
W‧‧‧Wound

Figure 1 is a schematic illustration of a first embodiment of a wet wound dressing of the present invention.

Figure 2 is a schematic illustration of the operation of the first embodiment of the wet wound dressing of the present invention.

Figure 3 is a cross-sectional view of a second embodiment of the wet wound dressing of the present invention applied to a wound.

4 to 6 are cross-sectional views showing the stage of the second embodiment shown in Fig. 3.

100‧‧‧Hydrophilic polyurethane foam

110‧‧‧Contact layer

111‧‧‧First hole

120‧‧‧absorbing layer

121‧‧‧Second hole

200‧‧‧ breathable layer

S‧‧‧ skin

W‧‧‧Wound

Claims (10)

A wet wound dressing formed by a hydrophilic polyurethane foaming system formed by foaming a hydrophilic polyurethane and a foaming component, wherein the hydrophilic polyurethane is first The polyether polyol is reacted with a polyisocyanate, and then reacted with a second polyether polyol to form a star-shaped polyurethane, wherein the first polyether polyol contains at least three terminal hydroxyl groups, and the hydrophilic polyurethane foam The holes are discontinuous closed holes. The wet wound dressing of claim 1, wherein the hydrophilic polyurethane foaming system comprises a contact layer and an absorbent layer, and the contact layer and the absorbent layer are integrally formed, wherein the contact layer is There are a plurality of first holes, and the absorbing layer has a plurality of second holes larger than the plurality of first holes. The wet wound dressing of claim 1, wherein the foaming component comprises a blowing agent, water, a surfactant, a polyamine, and a catalyst. The wet wound dressing of claim 1, wherein the first polyether polyol is poly(propylene glycol) triol. The wet wound dressing of claim 1, wherein the second polyether polyol is polyethylene glycol. The wet wound dressing of claim 1, wherein the polyisocyanate content is in the range of 20 to 70 mol% of the hydrophilic polyurethane. The wet wound dressing of claim 2, wherein the content of the first polyether polyol and the second polyether polyol in the hydrophilic polyurethane foam is in the range of the hydrophilic polyurethane 20~70mol%. The wet wound dressing of claim 2, further comprising a gas permeable layer formed of the hydrophilic polyurethane, disposed on one side of the absorbent layer, the first polyether in the gas permeable layer The content of the polyol and the second polyether polyol is in the range of 20 to 70 mol% of the hydrophilic polyurethane. The wet wound dressing according to claim 2, wherein the contact layer is scraped on the surface of the hydrophilic polyurethane foam when the hydrophilic polyurethane foam is formed, and then a predetermined pressure is applied. Formed. The wet wound dressing of claim 9, wherein the predetermined pressure ranges from 100 to 300 g/cm ² .