CN1579559A - Dressing material containing medicine chitoholosida and its preparation method - Google Patents

Abstract

The polyvinyl alcohol hydrogel dressing containing medicine and chitosan was prepared by cross-linking with ⁶⁰ Co γ-rays or high-energy electron beams. The solid component of the hydrogel dressing is composed of synthetic and natural solid polymers, and an appropriate amount of moisturizing agent, plasticizer, medicine, etc. are added, and the solvent is twice distilled water, physiological saline or phosphate neutral buffer solution. This kind of hydrogel dressing can slowly release drugs and natural polysaccharide chitosan with biological antibacterial activity, has active antibacterial ability, and has the characteristics of high water content, good water retention, moderate mechanical strength, light transmission and good air permeability , can meet the requirements of wet treatment of various wounds, not only as a permanent dressing for mild skin wounds or chronic skin diseases, but also for immediate closure of severe skin tissue wounds or burn wounds.

Description

Polyvinyl alcohol hydrogel dressing containing medicine and chitosan and preparation method thereof

technical field

The invention relates to a polyvinyl alcohol hydrogel dressing containing medicine and chitosan and a preparation method thereof.

Background technique

In the past, dry treatment methods were used for wounds such as knife wounds and burns, but wet treatment was proposed in the early 1960s. Moisturizing the wound can reduce pain and speed up wound healing. In treating burns, for example, wounds heal faster if blisters don't rupture, suggesting that maintaining fluid seepage from wounds is also a factor in promoting wound healing. Traditional medicine treats various skin injuries such as dry burns, wounds, scalds and bedsores. In order to protect the wound surface, reduce infection and accelerate wound healing, sterile gauze or gauze soaked in antibacterial solution is generally used to treat the wound. However, gauze is easy to adhere to the wound , form scabs, new epithelial and granulation tissue are often destroyed when changing dressings, the patient suffers from unbearable pain, the most important thing is that sterile gauze or gauze soaked in antibacterial solution cannot prevent the loss of water and electrolytes while absorbing wound secretions . In addition, for larger skin wounds, autologous, allogeneic or xenogeneic skin grafts still need to be applied. The sources of autologous and homologous skin transplantation are limited. Transplantation of allogeneic skin such as pig skin can cause strong rejection. The allergens in the allogeneic skin must be removed, leaving only collagen fibers, or the use of autologous epithelial cell culture membrane in vitro requires a lot of effort. Complicated process technology is expensive.

Synthetic water-soluble polymers such as polyvinyl alcohol, polyvinylpyrrolidone, polyacrylic acid, partially neutralized polyacrylic acid, polyethylene oxide, polyacrylamide, etc. have the advantages of wide sources and low prices. In the literature of various countries, there have been reports and examples of such materials being widely used as tissue filling materials, cartilage materials, drug coatings and drug carriers, which prove that this type of polymer material has good biological inertia and biocompatibility . Different water-soluble polymers are dissolved in water to make an aqueous solution, which can be cross-linked into a gel under the irradiation of ⁶⁰ Co γ-rays or high-energy electron beams, and an appropriate irradiation dose is selected to put a certain concentration of The polymer solution is irradiated and cross-linked into a hydrogel. Used as a wound dressing, this type of hydrogel has the following advantages: the main component is water, with a large heat capacity, making people feel cool; absorbing wound secretions without adhesion; good light transmission, easy for doctors to observe the healing of the wound; Water and oxygen have good permeability and do not allow bacteria to pass through, which can prevent infection caused by the external environment; with a space network structure, the required drugs can be embedded in it, and the drugs are slowly and continuously released to the lesion to achieve a cure The purpose of wounds and other skin diseases; the most important thing is that a large number of studies have proved that the hydrogel dressing made of the above materials has good biocompatibility and will not cause rejection or infection of the wound.

In the existing patent literature about hydrogel dressings, Chinese patent CN 1225370 introduces a radiation grafting method for medical polymer hydrogel membranes. The hydrogel film uses polyethylene oxide, polyvinyl alcohol, and water as raw materials, and is made into a hydrogel film through technological steps such as film casting, cold and heat cycle treatment, and radiation processing. Although this kind of hydrogel film has the ability to absorb and maintain wound exudate, the hydrogel does not contain moisturizing ingredients with specific functions, resulting in limited water retention capacity, and there is no antibacterial drug that can be used locally in the hydrogel , does not have the sustained release function of the drug, which increases the risk of infection in the wound and increases the workload of medical staff to change the dressing frequently.

Chinese patent CN 1121876 discloses a hydrogel composite wound dressing and its radiation synthesis method. This dressing is composed of a highly water-absorbent hydrogel synthesized by radiation cross-linking and a breathable and moisture-permeable polymer film. This kind of hydrogel film has moisture permeability and air permeability, but the same as CN 1225370, there is no pharmaceutical composition that can inhibit or kill bacteria in the gel, does not possess active antibacterial ability, and is easy to cause wound infection.

CN 2383500 provides a hydrogel composite wound dressing. This utility model patent only provides convenience for the use of the hydrogel film disclosed in CN 1121876, and does not improve the function.

Contents of the invention

The purpose of the present invention is to provide a medical hydrogel dressing containing medicine and chitosan, which has good antibacterial properties, appropriate biological activity, superior water absorption, water retention, air permeability, flexibility, and low cost , so that it can meet the requirements of modern medicine for dressings to the greatest extent;

Another object of the present invention is to provide a method for preparing a medical hydrogel dressing containing medicine and chitosan; the hydrogel dressing prepared by the method can improve the mechanical strength of the hydrogel and meet the requirements for clinical use of the dressing;

The third object of the present invention is to provide a kind of application of the medical hydrogel dressing containing medicine and chitosan; The hydrogel dressing prepared with this method is used for the treatment of superficial burn, knife wound, bed sore, skin cancer wound , It can also be used as a temporary dressing for wound closure before skin transplantation in the treatment of large and severe burns.

Polyvinyl alcohol hydrogel has good biocompatibility, and the hydrogel prepared from it has strong mechanical strength, but the disadvantage is lack of toughness.

Polyvinylpyrrolidone has excellent water solubility, film-forming property, and biocompatibility, and has good adhesion and flexibility after film formation, but the strength of the formed gel is not ideal.

The hydrogel prepared by radiation cross-linking of polyethylene oxide has water absorption, moderate water retention capacity, good flexibility, good drug resistance, low toxicity, and is suitable for biological materials. However, polyethylene oxide gel is easy to absorb water and swell, and the gel strength will drop significantly after swelling, which is not conducive to clinical use and operation.

Polyacrylic acid is easy to cross-link under radiation conditions, and the resulting gel has good adhesion and mechanical strength. Polyacrylic acid and acrylic acid-acrylamide copolymer hydrogel have good water absorption, and have strong retention after absorbing water. ability.

Natural water-soluble polymers such as agar, k-carrageenan, chitin, chitosan, gelatin, etc. have unique biocompatibility and bioactivity, and can be used as effective components of hydrogel dressings. When preparing medical hydrogel dressings by radiation method, adding a certain proportion of natural polymers to the water-soluble natural polymer solution can improve the biocompatibility of the hydrogel; at the same time, the natural polymers can be filled after being degraded by radiation. In the voids of the gel network, it plays a role in improving the gel strength.

Chitin is a polysaccharide linked by N-acetyl-2-amino-2-deoxy-D-glucose in the form of β-1,4 glycosidic bonds, and chitosan is the product of deacetylation of chitin. Chitin or chitosan, especially low-molecular-weight chitosan, has a significant antibacterial effect on skin bacteria such as Staphylococcus epidermidis, Pseudomonas aeruginosa, Staphylococcus aureus and Streptococcus pyogenes that exist in the general human epidermis. Bacteria, etc. have obvious inhibitory effect. At the same time, chitosan can promote the regeneration of epithelial cells, accelerate the speed of wound healing, and improve the quality of wound healing. Large molecular weight chitosan can be biodegraded to produce oligosaccharides, oligosaccharides, and even monosaccharides, thereby exerting its functions of accelerating cell proliferation and strengthening tissue remodeling. It is meaningful that large molecular weight chitosan has good film-forming strength, and small molecular weight chitosan has high biological activity and good water retention. Combining large molecular weight chitosan and small molecular weight chitosan can give full play to their respective advantages. Advantages, the preparation of medical dressings with excellent performance.

Adding a certain amount of plasticizer and humectant when preparing the hydrogel can improve or enhance the flexibility and water retention of the medical hydrogel dressing.

Adding drugs for different types of skin wounds in medical hydrogel dressings, such as antibacterial drugs, disinfectants, anti-inflammatory drugs, analgesics, hemostasis, coagulation drugs, water-soluble anticancer drugs, etc., can make hydrogel dressings have therapeutic properties. effect. The drug content in the hydrogel can be very large. After the drug on the surface of the gel is consumed, the drug inside the gel can be continuously replenished through migration and diffusion, so as to realize the continuous and slow release of the drug and reduce the frequent replacement of medical staff. It also reduces the burden of medication and reduces the risk of wound bacterial infection due to untimely dressing changes.

In the present invention, polyvinyl alcohol is respectively compounded with polyvinylpyrrolidone, polyethylene oxide, polyacrylic acid or acrylic acid-acrylamide copolymer to form polymer interpenetrating network hydrogel, which can be combined with polyvinyl alcohol hydrogel to form The high strength of the film, the flexibility and adhesion of polyvinylpyrrolidone and polyethylene oxide hydrogel film-forming; the strong water absorption and water retention of polyacrylic acid or acrylic acid-acrylamide copolymer hydrogel, thus preparing Medical wound dressing hydrogels with different characteristics and meeting different requirements.

The hydrogel dressing provided by the invention is composed of a solid polymer with a mass fraction of 10-30%, a plasticizer with a mass fraction of 1-10%, a humectant with a mass fraction of 1-10%, medicine and a solvent in the remainder .

The solid polymer is polyvinyl alcohol, polyvinylpyrrolidone, polyacrylic acid, acrylic acid-acrylamide copolymer, polyethylene oxide, chitosan, gelatin, carrageenan or agar.

The degree of polymerization of polyvinyl alcohol is 1500-3000, and the degree of alcoholysis is 98-100%.

The weight average molecular weight of polyvinylpyrrolidone is 3.0×10 ⁵ -1.5×10 ⁶ g mol ^-1 .

The mass ratio of acrylic acid to acrylamide monomers in the acrylic acid-acrylamide copolymer is 3:7.

The viscosity-average molecular weight of polyethylene oxide is 1.5×10 ⁵ -2.0×10 ⁶ g mol ^-1 .

The molecular weight of chitosan is 1000-1.5×10 ⁶ g mol ^-1 , and the deacetylation degree of chitosan is 80-98%.

The plasticizer of the present invention is selected from glycerin, ethylene glycol, propylene glycol or/and polyethylene glycol, and the mass percentage of the plasticizer can be 1-10%, wherein the molecular weight of polyethylene glycol is 100-1000g mol ^-1 .

The moisturizing agent used in the present invention is glycerin, ethylene glycol or propylene glycol or/and polyethylene glycol with a molecular weight of 100-1000 g mol ^-1 , sorbitol, small molecular weight water-soluble chitosan or hyaluronic acid.

The drugs added in the gel are all water-soluble drugs that can be used locally, and the antibacterial drugs can be polymyxin B, nystatin or ampicillin B, ciprofloxacin; Different types of trauma to be treated, with optional addition of different drugs:

Disinfection and antiseptic drugs: chlorhexidine or Jieermii;

Blood clotting drugs: phensulfame or tranexamic acid;

Anesthetics: Chlorobutanol;

Water-soluble anticancer drug: doxorubicin.

In the solid composition of the gel, a combination of polyvinyl alcohol and any of several polymers including polyvinylpyrrolidone, polyethylene oxide, polyacrylic acid or acrylic acid-acrylamide copolymer, combined with chitosan One or more of gelatin, carrageenan or agar form the solid components of the medical hydrogel dressing. Concrete combination is as follows, and each component content is mass percent composition:

(1) Polyvinyl alcohol 5-20%/ polyvinylpyrrolidone 2-15%/ chitosan 0.5-5%;

(2) Polyvinyl alcohol 5-20%/ polyvinylpyrrolidone 2-15%/ agar 0.1-3%/ chitosan 0.5-5%;

(3) Polyvinyl alcohol 5-20%/ polyvinylpyrrolidone 2-15%/ carrageenan 0.1-5%/ chitosan 0.5-5%;

(4) Polyvinyl alcohol 5-20%/ polyethylene oxide 2-15%/ chitosan 0.5-10%;

(5) Polyvinyl alcohol 5-20%/ polyethylene oxide 2-15%/ carrageenan 0.1-10%/ chitosan 0.5-10%;

(6) Polyvinyl alcohol 5-20%/acrylic acid-acrylamide copolymer 2-15%/chitosan 0.5-10%;

(7) Polyvinyl alcohol 5-20%/acrylic acid-acrylamide copolymer 2-15%/polyvinylpyrrolidone 1-10%/chitosan 0.5-10%;

(8) Polyvinyl alcohol 5-20%/ polyacrylic acid 2-15%/ chitosan 0.5-10%;

(9) Polyvinyl alcohol 5-20%/ polyethylene oxide 2-15%/ gelatin 1-10%/ chitosan 0.5-10%;

(10) Polyvinyl alcohol 5-20%/ polyvinylpyrrolidone 2-15%/ gelatin 1-10%/ chitosan 0.5-10%.

The medical hydrogel dressing containing medicine and chitosan of the present invention is made by following method:

(1) Dissolve polyvinyl alcohol in double distilled water, normal saline or phosphate neutral buffer solution to make solution A; One or more of ethane is dissolved in double distilled water, normal saline or phosphate neutral buffer solution to make solution B; combine solution A and solution B, mix well, and add 1-10% plasticizer 1-10% humectant, heat and stir to make it completely dissolve into a uniform solution;

(2) Leave the above solution at room temperature for 8-14 hours or vacuumize;

(3) Pour the solution into a polyethylene plastic bag and press it into a film with a thickness of about 1-5mm;

(4) Perform freezing-melting cycle treatment on the diaphragm, the freezing temperature is -30--20°C, the freezing time is 8-30 hours, the melting temperature is 20-30°C, the freezing and melting time is 8-30 hours, and the freezing- The number of melting cycles is 1-7 times;

(5) irradiating and cross-linking the hydrogel membrane processed by freezing-melting cycles at room temperature with ⁶⁰ Co gamma-rays or high-energy electron beams, and the irradiation dose is 10-80 kGy;

(6) natural ventilated drying, room temperature vacuum drying or freeze-drying, the hydrogel membrane part dehydration that has been irradiated, radiation sterilization, the part dry hydrogel membrane after the sterilization is immersed in containing mass percent under aseptic condition 0.1-2.0% water-soluble drug and 10.0% water-soluble chitosan with a molecular weight of less than 6000g mol ^-1 in double distilled water, normal saline or phosphate neutral buffer solution, wait for water coagulation Take out the glue after it swells to equilibrium, package it under aseptic conditions, and store it at a low temperature of 0-4°C.

Steps (4) and (5) can be carried out in reverse order, that is, the hydrogel membrane with a thickness of about 1-5 mm is irradiated and cross-linked at room temperature by ⁶⁰ Co gamma-rays or high-energy electron beams, and the irradiation dose is 10-80 kGy; The irradiated membrane is subjected to freezing-melting cycle treatment, the freezing temperature is -30--20°C, the freezing time is 8-30 hours, the melting temperature is 20-30°C, the freezing and melting time is 8-30 hours, and the freezing- The number of melting cycles is 1-7 times;

The medical hydrogel dressing containing medicine and chitosan prepared by the above materials and methods can be used for the treatment of various skin wounds such as shallow burns, knife wounds, bedsores, skin cancers, etc., and can also be used as a treatment for large area severe burns Temporary dressing for wound closure prior to skin grafting.

Detailed ways

The present invention is further illustrated below by way of examples, but the present invention is not limited thereto.

The performance testing method of hydrogel in following each embodiment, briefly describes as follows:

(1) Mechanical properties: measured by instron 1121 universal tensile machine, the tensile speed is 10mm/min, the length of the spline is 20.0mm, and the width is 4.0mm;

(2) Equilibrium water absorption: the ability of the hydrogel to absorb double distilled water at 20°C after freeze-drying: equilibrium water absorption % = (gel weight after water absorption balance - gel dry weight before water absorption) / gel dry weight before water absorption × 100%;

(3) Gel fraction: After the hydrogel is freeze-dried, use twice-distilled water as a solvent and extract with a Soxhlet extractor for 30 hours;

Gel fraction=(dry weight of gel before extraction-dry weight of gel after extraction)/dry weight of gel before extraction×100%.

(4) The listed percentages are mass percent concentrations, the viscosity-average molecular weight of chitosan is represented by Mn, and the degree of deacetylation is represented by DD.

Example 1

1). Take 90.0 g of double distilled water and 20.0 g of polyvinyl alcohol to make solution A, wherein the degree of polymerization of polyvinyl alcohol is 1500, and the degree of alcoholysis is 98%;

2). Take 50.0 g of twice distilled water and 8.0 g of polyvinylpyrrolidone to completely dissolve the polyvinylpyrrolidone into a homogeneous solution B. The weight average molecular weight of polyvinylpyrrolidone is 8.0×10 ⁵ g mol ⁻¹ ;

3). After mixing solution A and solution B, add 4.0 g of carrageenan, 10.0 g of glycerin, 10.0 g of polyethylene glycol 400, chitosan, double-distilled water and acetic acid mixed solution, and stir at constant temperature for 2 hours to obtain solution 3. The polysaccharide molecular weight is 1.0×10 ⁶ g mol ^-1 , DD=80.0%, the concentration of acetic acid is 3.5%, and the solid polymer content in solution 3 is 18%;

4). Put the solution 3 at room temperature for 8 hours, then pour the solution into a polyethylene plastic bag, seal it, press the film to a thickness of 1 mm, and cycle the freezing-melting process for 7 times in a circulating freezer, and irradiate it with ⁶⁰ Co gamma-rays at room temperature. According to cross-linking, the dose is 10kGy;

5). After 90% freeze-dehydration of the irradiated cross-linked hydrogel film, sterilize it by radiation, and immerse it in physiological salt with the concentration of 10.0% and 0.2% chitosan and ciprofloxacin lactate at 30°C under sterile conditions In the aqueous solution, the hydrogel is swelled and taken out after reaching equilibrium, packaged under aseptic conditions, and stored at a low temperature of 0°C. The chitosan molecular weight M _η =3000g mol ^-1 , DD ≥ 95%.

The properties of the hydrogel are shown in Table 1.

Example 2

1). Take 90.0g of normal saline and 20.0g of polyvinyl alcohol to make solution A, wherein the degree of polymerization of polyvinyl alcohol is 3000, and the degree of alcoholysis is 98%;

2). Take 50.0 g of normal saline and 10.0 g of polyvinylpyrrolidone to prepare solution B, wherein the weight average molecular weight of polyvinylpyrrolidone is 1.3×10 ⁶ g mol ⁻¹ ;

3). After mixing solution A and solution B, add 40.0g glycerin, chitosan, normal saline, and acetic acid mixed solution to obtain solution 3, in which 10.0g chitosan, chitosan molecular weight 5.0×10 ⁵ gmol ^-1 , DD =98.0%, glycerin 20.0g, solution 3 solid polymer content 20%;

4). The lamination process is the same as that in Example 1, the lamination thickness is up to 5 mm, the cycle freezer freeze-melt cycle treatment is performed once, ⁶⁰ Co gamma-rays are irradiated at room temperature for cross-linking, and the dose is 80 kGy;

5). The treatment process is the same as in Example 1, but the gel with a dryness of 30% under natural ventilation conditions is immersed in a physiological saline solution of 10.0% and 0.5% respectively in chitosan and chlorhexidine concentrations at 30°C, Store at low temperature at 4°C, chitosan M _η =3000g mol ^-1 , DD≥95%.

The properties of the hydrogel are shown in Table 1.

Example 3

1). Weigh 20.0 g of polyvinyl alcohol and dissolve it in 90.0 g of double-distilled water to make solution A, wherein the degree of polymerization of polyvinyl alcohol is 2500, and the degree of alcoholysis is 100%;

2). Dissolve 10.0 g of polyethylene oxide in 50.0 g of double-distilled water to prepare solution B, wherein polyethylene oxide Mη=6.3×10 ⁵ g mol ⁻¹ ;

3). After mixing solution A and solution B, add 4.0 g of carrageenan, 40.0 g of glycerin, polyethylene glycol 200, and secondary water, and stir for 2 hours to obtain solution 3, which contains 4.0 g of glycerin, polyethylene glycol 100 10.0g, solid polymer content 17% in solution 3;

4). The lamination process is the same as in Example 1, the lamination thickness is up to 3mm, the cycle freezer freeze-melt cycle treatment is performed 3 times, and ^{the 60} Co gamma-ray irradiation crosslinks with a dose of 30kGy;

5). The treatment process is the same as in Example 1, but the gel dried in vacuum at room temperature is immersed in a physiological saline solution with a concentration of 10.0% and 0.1% of chitosan and polymyxin B at 20°C, and stored at a low temperature of 2°C , chitosan M _η =3000g mol ^-1 , DD≥95%.

The properties of the hydrogel are shown in Table 1.

Example 4

1). Weigh 20.0 g of polyvinyl alcohol and dissolve it in 90.0 g of twice-distilled water to make solution A, wherein the degree of polymerization of polyvinyl alcohol is 2000, and the degree of alcoholysis is 98.5%;

2). Take 10.0 g of polyvinylpyrrolidone and add 50.0 g of secondary water to make solution B. The weight average molecular weight of polyvinylpyrrolidone is 1.2×10 ⁶ g mol ⁻¹ ;

3). After mixing solution A and solution B, add 10.0% (w) chitosan acetic acid aqueous solution 35.0g, add 30.0% (w) gelatin aqueous solution 15.0g, add glycerin 5.0g, sorbitol 4.0g, 80 ℃ Stir for 2 hours to obtain solution 3, the solid polymer content in solution 3 is 20%, chitosan M _η =5.0*10 ⁵ g mol ^-1 , DD = 95%,;

4). The lamination process is the same as in Example 1, the lamination thickness is up to 3mm, the cycle freezer freeze-melt cycle treatment is performed 3 times, and ^{the 60} Co gamma-ray irradiation crosslinks with a dose of 30kGy;

5). The treatment process is the same as in Example 1, but the freeze-dried gel is immersed in a neutral phosphate buffer solution with a concentration of 10.0% and 0.5% of chitosan and chlorobutanol at 20°C, and the chitosan Sugar M _η =1000 g mol ^-1 , DD≥95%.

The properties of the hydrogel are shown in Table 1.

Example 5

1). Take 80.0 g of phosphate neutral buffer solution and 20.0 g of polyvinyl alcohol to make solution A, wherein the degree of polymerization of polyvinyl alcohol is 2000, and the degree of alcoholysis is 98.5%;

2). Take 10.0 g of polyvinylpyrrolidone and add 50.0 g of phosphate neutral buffer solution to make solution B, wherein the weight average molecular weight of polyvinylpyrrolidone is 1.2×10 ⁶ g mol ⁻¹ ;

3). After mixing solution A and solution B, add 10.0% chitosan molecular weight acetic acid aqueous solution 35.0g, glycerin 6.0g, polyethylene glycol 800 4.0g, after sealing, stir at 80°C for 2h to make solution 3, in solution 3 The solid polymer content is 17%, and the molecular weight of chitosan is 5.6×10 ⁴ g mol ^-1 , DD≥95%;

4). The lamination process is the same as in Example 1, the lamination thickness is up to 3 mm, the freeze-thaw cycle is processed 3 times in a circulating refrigerator, and ⁶⁰ Co γ-rays are irradiated for cross-linking, with a dose of 30 kGy;

5). The treatment process is the same as in Example 1, but the freeze-dried gel is immersed in the physiological saline solution with chitosan and doxorubicin concentrations of 10.0% and 0.1% respectively at 20°C, and the chitosan M _η =3000g mol ⁻¹ , DD≥95%.

The properties of the hydrogel are shown in Table 1.

Example 6

1). Dissolve 10.0 g of polyvinyl alcohol in 90.0 g of twice-distilled water to make solution A, wherein the degree of polymerization of polyvinyl alcohol is 2000, and the degree of alcoholysis is 98.5%;

2). Take 50.0 g of acrylic acid-acrylamide (mass ratio = 3:7) copolymer aqueous solution (containing 10.0 g of polymer solids, add 30.0 g of double distilled water to completely dissolve the polymer, and make solution B.

3). After solution A and solution B are mixed, add 10.0 g of glycerin, and the total solid polymer content is 10%;

4). The lamination process is the same as in Example 1, the lamination thickness is up to 3 mm, the cycle freezer freeze-melt cycle is processed 3 times, ⁶⁰ Co gamma-rays are irradiated and cross-linked at room temperature, and the dose is 30 kGy;

5). The treatment process is the same as in Example 1, but the freeze-dried gel is immersed in the double-distilled aqueous solution whose concentrations of chitosan and tranexamic acid are respectively 10.0% and 2.0% at 40°C, wherein chitosan M _η = 3000 g mol ^-1 , DD ≥ 95%.

The properties of the hydrogel are shown in Table 1.

Example 7

1). Take 12.0 g of polyvinyl alcohol and dissolve it in 60.0 g of double distilled water, wherein the degree of polymerization of polyvinyl alcohol is 2000, and the degree of alcoholysis is 98.5%;

2). Take 50.0 g of acrylic acid-acrylamide mass ratio = 3:7 copolymer aqueous solution, containing 9.0 g of polymer solids, and add 30.0 g of double distilled water to completely dissolve the polymer;

3). Take 8.0 g of polyvinylpyrrolidone, add 30.0 g of double-distilled water to completely dissolve the polymer, and the weight-average molecular weight of polyvinylpyrrolidone is 1.2×10 ⁶ g mol ⁻¹ ;

4). After mixing the solutions prepared in steps 1, 2, and 3, add 35.0 g of 10.0% chitosan acetic acid aqueous solution, 4.0 g of propylene glycol, and 3.0 g of polyethylene glycol 200, seal it, stir at 80 ° C for 2 hours, and obtain solution 4 , the solid polymer content is 18%, the molecular weight of chitosan is 5.0×10 ⁵ g mol ^-1 , DD≥95%;

5). The laminating process is the same as that in Example 1, after freezing and melting once, ⁶⁰ Co gamma-rays are irradiated at room temperature for cross-linking, and the dose is 40 kGy;

6). The treatment process is the same as in Example 1, but the freeze-dried gel is immersed in the double-distilled aqueous solution of 10.0% and 0.5% of the concentration of chitosan and phensulfacetate at 40° C., and the chitosan M _η = 3000g mol ^-1 , DD≥95%.

The properties of the hydrogel are shown in Table 1.

Example 8

1). Take 90.0 g of twice distilled water and 20.0 g of polyvinyl alcohol to completely dissolve the polyvinyl alcohol to prepare solution A, wherein the polyvinyl alcohol has a degree of polymerization of 2000 and a degree of alcoholysis of 98.5%;

2). Take 50.0 g of twice-distilled water, add 8.0 g of polyvinylpyrrolidone under stirring, and completely dissolve the polyvinylpyrrolidone into a uniform solution to prepare solution B; the weight-average molecular weight of polyvinylpyrrolidone is 1.2×10 ⁶ g mol ^{- 1} ;

3). Mix solution A and solution B, add 6.0 g of glycerin, 4.0 g of polyethylene glycol 200, and a mixed solution of chitosan acetic acid aqueous solution, stir at constant temperature for 2 hours, and obtain solution 3, wherein chitosan M _η =5.0×10 ⁵ g mol ^-1 , DD≥95%, the solid polymer content in solution 3 is 16%;

4). Solution 3 was left to stand at room temperature for 12 hours, poured into a polyethylene plastic bag, sealed, and pressed to a thickness of 3 mm. Freezing-melting cycle treatment is performed 3 times in a circulating freezer, and high-energy electron beams are irradiated and cross-linked at room temperature, with a dose of 30kGy;

5). The treatment process is the same as in Example 1, but the hydrogel film is immersed in 35°C chitosan and 10.0% and 0.5% physiological saline solution respectively, and stored at a low temperature of 4°C. Chitosan M _η = 3000 g mol ^-1 , DD ≥ 95%.

Example 9

1). Take 90.0 g of twice distilled water and 20.0 g of polyvinyl alcohol to completely dissolve the polyvinyl alcohol to prepare solution A, wherein the polyvinyl alcohol has a degree of polymerization of 2000 and a degree of alcoholysis of 98.5%;

2). Take 50.0 g of twice-distilled water, add 8.0 g of polyvinylpyrrolidone under stirring, and completely dissolve the polyvinylpyrrolidone into a uniform solution to prepare solution B; the weight-average molecular weight of polyvinylpyrrolidone is 1.2×10 ⁶ g mol ^{- 1} ;

3). Mix solution A and solution B, add 6.0 g of glycerin, 4.0 g of polyethylene glycol 200, and a mixed solution of chitosan acetic acid aqueous solution, and stir at a constant temperature for 2 hours to obtain solution 3. The total solid polymer content is 16%, and the shell Glycan M _η =5.0×10 ⁵ g mol ^-1 , DD≥95%;

4). Solution 3 was allowed to stand at room temperature for 12 hours, pour the solution into a polyethylene plastic bag, seal it, and press the film to a thickness of 3mm; irradiate and cross-link with high-energy electron beam rays at room temperature, with a dose of 80kGy, and freeze in a circulating freezer- Melting cycle treatment once;

5). The treatment process is the same as that in Example 1, but the hydrogel film is immersed in the physiological saline solution with chitosan and chlorhydrin concentrations of 10.0% and 0.5% respectively at 40°C, and the chitosan M _η =3000g mol ^-1 , DD≥95%.

Example 10

1). Weigh 20.0 g of polyvinyl alcohol and dissolve it in 90.0 g of double-distilled water to make solution A, wherein the degree of polymerization of polyvinyl alcohol is 2500, and the degree of alcoholysis is 100%;

2). Dissolve 10.0 g of polyethylene oxide in 50.0 g of double-distilled water to prepare solution B, wherein polyethylene oxide Mη=6.3×10 ⁵ g mol ⁻¹ ;

3). After mixing solution A and solution B, add 4.0 g of carrageenan, 40.0 g of glycerin, polyethylene glycol 200, and secondary water, and stir for 2 hours to obtain solution 3, which contains 4.0 g of glycerin, polyethylene glycol 100 10.0g, solid polymer content 17% in solution 3;

4). The lamination process is the same as in Example 1, the lamination thickness is up to 3 mm, ⁶⁰ Co gamma-ray irradiation crosslinking, the dosage is 10 kGy, and the freezing-melting cycle treatment is 7 times in a circulating freezer;

5). The treatment process is the same as in Example 1, but the gel dried in vacuum at room temperature is immersed in a physiological saline solution with a concentration of 10.0% and 0.1% of chitosan and polymyxin B at 20° C., and chitosan M _η = 3000 g mol ^-1 , DD ≥ 95%.

The properties of the hydrogel are shown in Table 1.

Example 11

1). Weigh 20.0 g of polyvinyl alcohol and dissolve it in 90.0 g of double-distilled water to make solution A, wherein the degree of polymerization of polyvinyl alcohol is 2000, and the degree of alcoholysis is 98.5%;

2). Take 10.0 g of polyvinylpyrrolidone and add 50.0 g of secondary water to make solution B. The weight average molecular weight of polyvinylpyrrolidone is 1.2×10 ⁶ g mol ⁻¹ ;

3). After mixing solution A and solution B, add 10.0% (w) chitosan acetic acid aqueous solution 35.0g, add 30.0% (w) gelatin aqueous solution 15.0g, add glycerin 5.0g, sorbitol 4.0g, 80 ℃ Stir for 2 hours to prepare solution 3, chitosan M _η =5.0*10 ⁵ g mol ^-1 , DD = 95%, and the solid polymer content in solution 3 is 20%;

4). The lamination process is the same as in Example 1, the lamination thickness is up to 3 mm, ⁶⁰ Co gamma-ray irradiation crosslinking, the dosage is 30 kGy, and the freezing-melting cycle treatment of circulating freezer is 3 times,

5). The treatment process is the same as in Example 1, but the freeze-dried gel is immersed in a neutral phosphate buffer solution with a concentration of 10.0% and 0.5% of chitosan and chlorobutanol at 20°C, and the chitosan Sugar M _η =1000 g mol ^-1 , DD≥95%.

The properties of the hydrogel are shown in Table 1.

Attached table 1 is the performance of the medical hydrogel dressing containing medicine and chitosan prepared in each embodiment Example Gel fraction (%) Tensile strength (MPa) Elongation at break (%) Tensile load (N) Equilibrium Water Absorption (%) 1 70.3 0.568 190 4.48 330 2 60.7 0.619 248 3.32 315 3 72.5 0.599 267 4.47 300 4 59.2 0.452 260 2.61 227 5 58.3 0.669 160 3.32 265 6 50.2 0.712 250 3.53 532 7 90.3 0.650 300 3.62 282 8 75.0 0.560 350 3.41 300 9 82.5 0.620 150 3.10 250 10 45.2 0.470 300 2.70 340 11 58.2 0.420 270 2.30 350

Claims (3)

1. A polyvinyl alcohol hydrogel dressing containing medicine and chitosan, comprising a solid polymer of 10-20% by mass fraction, a plasticizer of 1-10% by mass fraction, and a mass fraction of 1-10% % of moisturizing agent, mass fraction of 0.1-2% of the drug and the remaining solvent composition; The solid polymer is polyvinyl alcohol and chitosan and one or more of the following: polyvinylpyrrolidone, polyacrylic acid, acrylic acid-acrylamide copolymer, polyethylene oxide, gelatin, carrageenan or agar; wherein The degree of polymerization of polyvinyl alcohol is 1500-3000, and the degree of alcoholysis is 98-100%; the mass ratio of acrylic acid to acrylamide in the acrylic acid-acrylamide copolymer is 3:7; the molecular weight of chitosan is 1000-1.0×10 ⁶ g mol ^-1 , the deacetylation degree of chitosan is 80-98%; The plasticizer is glycerin, ethylene glycol, propylene glycol or polyethylene glycol; the molecular weight of polyethylene glycol is 100-1000g mol ⁻¹ ; The moisturizing agent is one or several of the following reagents: chitosan, glycerin, ethylene glycol, propylene glycol, polyethylene glycol or sorbitol; the molecular weight of polyethylene glycol is 100-1000g mol ⁻¹ ; The drug is a water-soluble drug that can be used locally, and there are one or more of the following: antibacterial drug polymyxin B or ciprofloxacin; amine or tranexamic acid; anesthetic chlorobutanol; water-soluble anticancer drug doxorubicin; The solvent is double distilled water, physiological saline or phosphate neutral buffer solution. 2. a method for preparing the polyvinyl alcohol hydrogel dressing containing medicine and chitosan described in claim 1, its preparation step is: a) dissolving polyvinyl alcohol in double distilled water, normal saline or phosphate neutral buffer solution to make solution A; b) Dissolving one or more of the remaining polyvinylpyrrolidone, polyacrylic acid, acrylic acid-acrylamide copolymer or polyethylene oxide in double distilled water, normal saline or phosphate neutral buffer solution to prepare Solution B; c) Combine solution A and solution B, mix well, add chitosan, gelatin, carrageenan, one or more of agar, and add plasticizer, humectant to make hydrogel solution; d) After the hydrogel solution is allowed to stand at room temperature, it is heated to a fluid state to form a hydrogel film with a thickness of 1-5mm, which is subjected to cyclic freezing-melting treatment for 1-7 times; ⁶⁰ Co gamma-rays or high-energy electron beam rays Irradiation cross-linking, dose 10-80kGy; e) The radiation-crosslinked hydrogel film is naturally ventilated and dried, vacuum-dried or freeze-dried at room temperature, the degree of dehydration is 30-100%, the dehydrated hydrogel film is sterilized by radiation, and the sterilized partially dried hydrogel film is Immerse in double distilled water containing chitosan and drugs, physiological saline or phosphate neutral buffer solution under bacteria conditions, take out the hydrogel after it swells to equilibrium, seal it, and store it at a low temperature of 0-4°C. 3. step d) in the method for preparing the polyvinyl alcohol hydrogel dressing containing medicine and chitosan as claimed in claim 2) irradiation cross-linking at room temperature after the described cycle freeze-melt treatment, also can be room temperature Under ⁶⁰ Co gamma-rays or high-energy electron beam radiation cross-linking, the dose is 10-80kGy; cycle freezing-melting treatment 1-7 times.