CN1121876C - Hydrogel composite wound dressing and its radiation synthesis method - Google Patents

Abstract

A composite wound dressing is composed of high-hydroscopicity hydrogel synthesized by radiation cross-linking and air-permeable and moisture-permeable polymer film. The radiation synthesis process includes mixing the material for hydrogel with water, casting the solution in mold, curing, irradiating with electron beam or gamma ray in the irradiation dose of 15-100kGy, covering one side of the hydrogel with ventilating film, covering the other side with stripping film, cutting, bagging and radiation sterilizing. The product has good transparency, high water absorption, air permeability, and moisture permeability, but is impermeable to water, and can prevent wound infection and accelerate healing. Is suitable for protecting and treating wound surface of burn, scald, bedsore and traumatic wound. And can be stored for a long time after radiation sterilization.

Description

Hydrogel composite wound dressing and its radiation synthesis method

The invention relates to a composite wound dressing suitable for protection and treatment of burns, scalds, bed sores and traumatic wounds, its composition and preparation method.

Wound dressings used to protect and heal wounds can be divided into three categories:

1. Universal type - apply plaster on the wound surface, wrap and protect the wound with gauze, bandage, etc. This method cannot block bacteria and is not waterproof, which brings great inconvenience to patients' daily life. More importantly, gauze, bandages, etc. are often adhered to the skin and tissue, which brings great pain to the patient when changing the dressing and often causes the wound to rupture again.

2. Biological type - made of animal skin, sponge, amniotic membrane, etched membrane, plasma membrane, etc. This material has good air permeability and biocompatibility, which reduces the pain of patients when changing dressings. However, this material requires low temperature storage and is expensive, which restricts its promotion and use.

3. Composite type - made from synthetic polymers and made into foams, pastes, films, fabrics, etc. This type of wound dressing is suitable for industrial production and popularization, and has good water absorption and air permeability.

Currently, there are several types of composite wound dressings used for wound protection and treatment of burns, scalds, decubitus, and wounds:

1. Coat medical pressure-sensitive adhesive on polyvinyl chloride, polyethylene, polypropylene, non-woven fabric, polyurethane and other backing materials, and paste the prepared film on the wound surface. Using non-breathable materials such as polyvinyl chloride, polyethylene, polypropylene, etc. as backing materials will affect the normal breathing of the skin, and they are not absorbent. If this material is used for a long time, the skin will be corroded by sweat and wound exudate, which will cause adverse reactions such as allergies, and the adhesive on the film will easily fall off after soaking in water, which will affect the treatment. Polyurethane backing has good air permeability, but it also has the disadvantage of not absorbing water. The backing of non-woven fabric is breathable and can absorb evaporated water, but its open-pore structure cannot block bacteria; moreover, it is opaque, so the wound healing cannot be observed in time; the possibility of its adhesion to tissues cannot be ruled out when changing the dressing.

2. Three-layer composite wound dressing. Usually, a breathable continuous film is used as the protective backing layer; non-woven fabric, foam material or fiber fabric, etc. are used as the occlusion backing layer; and an adhesive layer bonded to the skin is composed of three layers. This structure has certain air permeability and water absorption capacity, but its water absorption capacity is not strong, and it is opaque, which affects the observation of the wound.

3. Hydrogel composite wound dressing. This type of dressing is usually composed of a breathable continuous film, a non-woven or fiber fabric skeleton, hydrogel, adhesive and other parts. Because hydrogel has good strength, flexibility and air permeability, it can provide a moist, breathable and comfortable environment for the wound, and can buffer the impact force given to the wound by the outside world. It is a real wound protection material. , especially suitable for wounds with a lot of exudate.

CN1044405 discloses a dressing that can absorb wound exudate and transfer moisture to the air. This wrapping tape is made of polyester, polyethylene and other films as a protective backing, and a layer of hydrogel with fiber fabric or non-woven fabric as a skeleton is pasted on the protective backing. Hydrogel base materials include sodium carboxymethylcellulose, various polyacrylamines, polyacrylonitrile and acrylic acid polymers, etc. The disadvantage of this hydrogel is that it is not transparent.

CN1095916 discloses a wound dressing capable of absorbing wound exudate. It is composed of polyurethane film and polymer mesh to form a closed top layer. The absorbent layer is composed of the first layer of polypropylene fiber, a mixture of hydrocolloid and superabsorbent, and the second layer of polypropylene fiber. The direct contact with the skin is polyethylene. A polymer base layer made of pyrrolidone or polyvinyl alcohol and an adhesive layer containing hydrocolloids. The invention claims to have excellent water absorption, but its multi-layer composite structure designed to achieve ideal strength and water absorption sacrifices transparency for viewing wounds.

CN2292547 discloses a water-absorbing medical dressing that does not stick to wounds, which consists of a water-absorbing layer made of microporous non-woven fabric coated with an acrylic water-absorbing resin film and a base layer made of fiber fabric or breathable non-woven fabric . In addition to the aforementioned shortcomings of being opaque and not blocking bacteria, this dressing also lacks ideal properties such as softness and elasticity that wound dressings should possess. In addition, the residual monomers of acrylic resins often have skin irritation or slight toxic side effects.

US5674523 discloses a self-adhesive hydrogel wound dressing, which is formed by laminating polyurethane film, polyolefin mesh and hydrogel. Its characteristic is that it is made into a long strip, which can be wrapped around the wrist and other parts; the polyolefin mesh has a rectangular window above the wound to observe the wound.

US4871490 discloses a method for manufacturing a hydrogel wound dressing. Mix polyacrylamide, polyvinylpyrrolidone, gelatin, polyethylene glycol and other components in different proportions to prepare an aqueous solution with a concentration of 2-20%, pour the aqueous solution into a mold with a certain shape, and finally use the electronic Beam irradiation above 25kGy becomes a hydrogel with good water absorption properties. However, the residual monomers of the polyacrylamide used in it are toxic and irritating to the human body.

EP0450671 discloses a method for the preparation of a wound dressing. The dressing is composed of a breathable high polymer film, a fiber layer and a radiation cross-linked hydrogel layer. The invention claims that the breathable polymer film is selected from materials such as silicone rubber, polyurethane, and polyether-polyester copolymer; in order to improve the adhesion between the back film and the hydrogel, polyester, polyamide, etc. are placed between them. , Polyurethane and other fiber fabrics are used as interlayers; the hydrogel is composed of polyvinyl alcohol and antibacterial agents, and is prepared by radiation crosslinking.

Although these existing hydrogel-type wound dressings solve the problems of absorbing exudate, air permeability, blocking bacteria, waterproofing, and wound comfort, in order to increase the strength of the hydrogel, strengthen the hydrogel and the waterproof and breathable back film Most of them use fiber fabric or non-woven fabric as the reinforcement layer, and adopt a complex process of multi-layer composite. In this case, the product is an opaque structure, which affects the observation of wound healing.

The purpose of the present invention is to provide a kind of can absorb exudate, can block bacteria, has the characteristics of transparent, breathable, waterproof, no adhesion with tissue, good flexibility, etc. Protective and therapeutic hydrogel composite wound dressings.

Another object of the present invention is to propose the composition of this wound dressing and its radiation synthesis method.

The hydrogel composite wound dressing of the present invention is composed of a gas permeable polymer film and a hydrogel layer, wherein the water content of the hydrogel is 75-95% by weight, and the degree of crosslinking of the hydrogel is 75-95% %, water absorption 200-400%.

Wherein the hydrogel is selected from one or more β-hydroxyethyl methacrylate, acrylate, polyvinylpyrrolidone, polyvinyl alcohol, polyethylene oxide, polyethylene glycol and other monomers or polymers formulated into aqueous solutions Curing, the hydrogel formed by cross-linking by electron beam or γ-ray irradiation with a radiation dose selected from 15-100kGy.

Wherein the polymer used in the hydrogel is selected from polyvinylpyrrolidone, polyvinyl alcohol and/or polyethylene oxide.

The ratio of polyvinylpyrrolidone to polyvinyl alcohol is 0:14 to 14:0 by weight, and the content of polyethylene oxide is 0-10% of the total weight of the hydrogel.

Wherein the ratio of polyvinylpyrrolidone to polyvinyl alcohol is 4:10 to 10:4 by weight.

Wherein the thickness of the hydrogel is 0.5 to 10 mm.

Wherein the polymer used for the air-permeable polymer film is selected from polyethylene, polyvinyl chloride, silicone rubber, polyurethane or polyimide.

Wherein the hydrogel can be covered with a release paper or release film coated with silicone.

The radiation synthesis method of the hydrogel composite wound dressing of the present invention is that the materials used in the hydrogel are mixed with water, the solution is poured in a mold, and after curing, the irradiation dose is selected from an electron beam of 15-100kGy or Gamma-ray irradiation, one side of the hydrogel is covered with a gas-permeable polymer film, cut, bagged and then sterilized by radiation.

Wherein, if necessary or desired, the other side of the hydrogel is covered with a silicone-coated release paper or release film.

The wound dressing proposed by the present invention includes a gas-permeable polymer film, a hydrogel synthesized by a radiation cross-linking method, and a silicone-coated release paper or a polymer film.

The breathable polymer film protects the hydrogel absorption layer, prevents excessive evaporation of water in the hydrogel, prevents bacterial invasion, and acts as a reinforcement for the hydrogel under the premise of maintaining normal skin respiration. The film must be a continuous film with good flexibility, and the material can be selected from polymers such as polyethylene, polyvinyl chloride, silicone rubber, polyurethane, and polyimide. The preferred material is polyurethane, and its water vapor transmission rate is greater than 300g/m ² ·24h. The thickness of the film is selected to be 25-100 microns, preferably 25-50 microns.

The hydrogel used as the absorbing layer in the present invention is synthesized by radiation cross-linking method, the cross-linking degree of the synthesized hydrogel is as high as 75-95%, the water absorption rate is 200-400%, and has good strength. Another advantage of radiation crosslinking to synthesize hydrogels is that no initiators are required, and chemical initiators are usually toxic chemicals, so synthesis by radiation methods can maintain the purity of the system.

The raw materials of the synthetic hydrogel are water-soluble polymers or monomers with good biocompatibility and no side effects on the human body, including β-hydroxyethyl methacrylate, acrylate polymers, polyvinylpyrrolidone, polyvinyl alcohol, Polyethylene oxide, polyethylene glycol, etc. Preferred materials are polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVA), polyethylene oxide (PEO). Select one or more of the above materials, mix them in a suitable proportion to make a solution, cast the solution in a mold, and after curing at room temperature, irradiate it with electron beams or gamma rays to make it cross-linked.

The ratio of polyvinylpyrrolidone and polyvinyl alcohol in the hydrogel is 0/14-14/0 (w/w), and the preferred ratio is 4/10-10/4 (w/w). The content is 0-10wt% of the total weight of the hydrogel. The water content of the hydrogel is 75-95% by weight. The thickness of the hydrogel is 0.5-10 mm, preferably 2-4 mm. The irradiation dose of electron beam or gamma ray is selected to be 15-100kGy, preferably between 25-50kGy.

Covered on the hydrogel, the peeling layer that needs to be torn off and discarded before use must have a certain adhesive force with the hydrogel, but it is easy to tear off. The material of this layer can be release film coated with silicone, polyethylene film, polypropylene film, polyvinyl chloride film and other release films.

In order to improve the adhesive performance of the gas-permeable film and the hydrogel, the surface of the gas-permeable film can be treated, the surface of the gas-permeable film can be coated with a medical adhesive, or the surface of the hydrogel can be coated with a viscous adhesive layer, using one of the above methods Or a combination of several methods can obtain satisfactory adhesion.

Composite the gas-permeable film, hydrogel and peel-off film described in the article, cut into certain specifications, seal and package with water-tight and air-tight packaging bags, and finally sterilize with electron beam or γ-ray irradiation. The hydrogel sterilized by irradiation can be stored at room temperature, and the storage period is more than two years. When in use, fix it with transparent and breathable medical tape, which can make it more firmly bonded and retain its waterproof, breathable and other functions.

The effective part of the wound dressing is composed of a superabsorbent hydrogel synthesized by radiation method and a continuous film of air-permeable polymer, and it is fixed to the skin with a transparent air-permeable pressure-sensitive adhesive tape. This kind of wound dressing is used for the wound protection of the above-mentioned kinds of wounds and has the following characteristics: it has high water absorption and can effectively absorb wound exudate; it has a closed top layer, which can effectively block bacteria and prevent wound infection; it contains a lot of water, And it has air permeability, moisture permeability, good strength and flexibility, can provide good comfort to the wound surface, and can promote wound healing; has good transparency, easy to observe wound healing; does not adhere to skin and tissue, replace There is no pain for the patient at the time, and no secondary trauma will be caused; all the formulas are made of materials with good biocompatibility and no toxic side effects on the human body, and the products have been strictly sterilized; they have good waterproof and anti-shedding properties, and will not affect the patient's bathing and normal activities and other daily activities. The wound dressing is suitable for the protection and treatment of burns, scalds, bed sores and traumatic wounds.

[Example 1]

Mix 8 grams of PVA and 92 grams of water to prepare an 8wt% PVA aqueous solution. The aqueous solution is cast in a petri dish, cured at room temperature for 1 hour, and then irradiated with γ-rays at 15 kGy. One side of the prepared hydrogel is covered with a polyurethane film coated with medical pressure-sensitive adhesive, and the other side is covered with a polyethylene film, cut into shape, put into a plastic bag and sealed, and sterilized by gamma ray irradiation.

The degree of crosslinking of the hydrogel is 80%, the water absorption rate is 170%, the tensile strength is 270g/cm ² , and the elongation at break is 230%. [Example 2]

Mix 15 grams of PVP and 85 grams of normal saline to prepare a 15wt% PVP normal saline solution, cast the aqueous solution in a petri dish, and after solidifying at room temperature for 1 hour, stick a layer of surface-treated polyethylene film on its surface, and use γ Ray irradiation 25kGy. Paste release paper on the other side of the hydrogel, then cut, bag, and irradiate to sterilize.

The degree of cross-linking of the hydrogel is 94%, the water absorption rate is 260%, the tensile strength is 445g/cm ² , and the elongation at break is 250%. [Example 3]

4 grams of PVA, 10 grams of PVP, and 86 grams of water were mixed to prepare a PVA/PVP mixed solution with a solid content of 14 wt%. The solution was cast in a mold, and after curing at room temperature for 1 hour, a layer of pasty PVA solution was coated on the surface, and 25kGy was irradiated with an electron beam. One side of the hydrogel is covered with a polyurethane film, and the other side is covered with a polyvinyl chloride film, cut, bagged, and sterilized by radiation.

The degree of cross-linking of the hydrogel is 90%, the water absorption rate is 320%, the tensile strength is 340g/cm ² , and the elongation at break is 280%. [Example 4]

3 grams of PVA, 7 grams of PVP, and 90 grams of water were mixed to prepare a PVA/PVP mixed solution with a solid content of 10 wt%. The solution was cast in a mold, and after curing at room temperature for 1 hour, a layer of paste PVA solution was coated on the surface, and 40kGy was irradiated with an electron beam. One side of the hydrogel is covered with a silicone rubber film, and the other side is covered with a polyvinyl chloride film, cut, bagged, and sterilized by radiation.

The degree of crosslinking of the hydrogel is 85%, the water absorption rate is 230%, the tensile strength is 300g/cm ² , and the elongation at break is 250%. [Example 5]

10 grams of PVA, 4 grams of PVP, and 86 grams of water were mixed to prepare a PVA/PVP mixed solution with a solid content of 14 wt%. The solution was cast in a mold, and after curing at room temperature for 1 hour, it was irradiated with an electron beam of 50 kGy. One side of the hydrogel is covered with a polyvinyl chloride film, and the other side is covered with a polypropylene film, cut, bagged, and irradiated to sterilize.

The degree of crosslinking of the hydrogel is 84%, the water absorption rate is 230%, the tensile strength is 280g/cm ² , and the elongation at break is 260%. [Example 6]

12 grams of PVA, 8 grams of PEO, and 80 grams of water are mixed to prepare a PVA/PEO mixed solution with a solid content of 20 wt%. The solution was cast in a mold, and after curing at room temperature for 1 hour, it was irradiated with an electron beam of 90 kGy. One side of the hydrogel is covered with a polyimide film, and the other side is covered with a polypropylene film, cut, bagged, and irradiated to sterilize.

The degree of crosslinking of the hydrogel is 82%, the water absorption rate is 240%, the tensile strength is 380g/cm ² , and the elongation at break is 350%.

The performance of the hydrogel type wound dressing that the present invention makes is as follows: 1. degree of crosslinking: 80-95%

Test method: put the hydrogel in a sealed copper grid, place it in a beaker filled with deionized water, and heat the beaker in a high-pressure steam cooker with a temperature set at 125°C for two hours; put the deionized water in the beaker Pour off the water, replace with new deionized water, and heat for another two hours; repeat the previous step. Finally, the copper mesh was taken out and dried to constant weight. Calculate the weight of the hydrogel before and after extraction, and the percentage of the insoluble portion in hot water to the total amount of hydrogel solids is the degree of crosslinking. 2. Water absorption: 200-400%

Test method: Soak the hydrogel in deionized water for 5 days, wipe off excess water on the surface and weigh. The percentage of the hydrogel's weight gain (that is, the water absorbed by the hydrogel) to the original weight of the hydrogel is the water absorption. 3. Tensile strength: 250-500g/ ^cm2 Elongation at break: 100%-400%

Test method: cut the hydrogel into dumbbell-shaped specimens, and use the WD-10D tensile strength tester of Changchun No. 2 Testing Machine Factory to test. 4. Water vapor transmission rate: 800g/m ² ·24h (37℃, relative humidity 55%)

Test method: according to ASTM E96-80 standard. 5. Transparency: 75-85%

Test method: Measure the transmittance at 700nm with a UV-365 spectrophotometer from Shimadzu, Japan. 6. Bacterial permeability: Bacteria impenetrable

Test method: place nutrient agar cultured with Escherichia coli on one side of the hydrogel, place it in an incubator at 37°C, take it out after 5 days, and observe the bacterial growth on the other side of the hydrogel. 7. Bacterial content: not detected

Test method: according to GB4789.2-94 standard.

Claims (12)

1. A hydrogel composite wound dressing is characterized in that it is made up of an air-permeable polymer film and a hydrogel layer, wherein the water content of the hydrogel is 75-95% by weight, and the degree of crosslinking of the hydrogel is It is 75-95%, and the water absorption rate is 200-400%; the above-mentioned hydrogel is selected from one or more β-hydroxyethyl methacrylate, acrylate, polyvinylpyrrolidone, polyvinyl alcohol, polyethylene oxide, polyethylene glycol. 2. dressing according to claim 1, is characterized in that, described hydrogel is selected from one or more β-hydroxyethyl methacrylate, acrylate, polyvinylpyrrolidone, polyvinyl alcohol, poly Ethylene oxide and polyethylene glycol monomers or polymers are formulated into aqueous solutions and cured, and are cross-linked by electron beams or gamma-rays with an irradiation dose of 15-100 kGy to form hydrogels. 3. Dressing according to claim 2, characterized in that the polymer used in the hydrogel is selected from polyvinylpyrrolidone, polyvinyl alcohol and/or polyethylene oxide. 4. dressing according to claim 3, it is characterized in that the proportioning of polyvinylpyrrolidone and polyvinyl alcohol is 0: 14 to 14: 0 by weight, and the content of polyethylene oxide is 0-10% of the total weight of hydrogel. 10%. 5. The dressing according to claim 4, characterized in that the ratio of polyvinylpyrrolidone to polyvinyl alcohol is 4:10 to 10:4 by weight. 6. Dressing according to any one of claims 1-5, characterized in that the thickness of the hydrogel is 0.5 to 10 mm. 7. The dressing according to any one of claims 1-5, characterized in that the polymer used for the air-permeable polymer film is selected from polyethylene, polyvinyl chloride, silicone rubber, polyurethane or polyimide. 8. The dressing according to any one of claims 1-5, characterized in that the hydrogel can be covered with a release paper or peeling film coated with silicone. 9. Dressing according to claim 6, characterized in that the thickness of the hydrogel is 2 to 4 mm. 10. The radiation synthesis method of the dressing according to any one of claims 1-5, characterized in that the materials used in the hydrogel are mixed with water, the solution is poured in a mould, and the radiation dose is used after curing Choose 15-100kGy electron beam or γ-ray irradiation, one side of the hydrogel is covered with a gas-permeable polymer film, cut, bagged, and sterilized by radiation. 11. The radiation synthesis method according to claim 10, characterized in that the other side of the hydrogel is covered with a release paper or release film coated with silicone. 12. The radiation synthesis method according to claim 10, characterized in that the radiation dose is 25-50 kGy electron beam or γ-ray radiation.