CN112472874A - Antibacterial and non-irritant medical artificial skin - Google Patents
Antibacterial and non-irritant medical artificial skin Download PDFInfo
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Abstract
The invention discloses an antibacterial and nonirritating medical artificial skin which is prepared from artificial skin materials comprising a surface layer and an inner layer, wherein the surface layer is prepared by carrying out polycondensation reaction on 2, 4-dicarboxylthiazole and 1, 3-bis (4-hydroxybutyl) tetramethyldisiloxane to obtain a polycondensate, and then adding alginic acid for end capping; the inner layer is prepared from polycondensate prepared by the polycondensation of 6-amino-6-deoxy-alpha-D-glucopyranosyl 6-amino-6-deoxy-alpha-D-glucopyranoside and furan-2, 5 dicarboxylic acid, collagen and epidermal growth factor. The medical artificial skin disclosed by the invention has the advantages of good strength and elasticity, good permeability, capability of being tightly attached to a wound surface, no stimulation to the wound surface, strong antibacterial performance, excellent stability and safe and convenient use.
Description
Technical Field
The invention relates to the technical field of medical assistance, in particular to a material for artificial skin and a preparation method thereof.
Background
The skin is a barrier that allows us to maintain water balance in the body and protect people from dirt or bacteria. When a large area of skin is severely burned, scalded or damaged, the skin cannot be repaired by itself, and superficial skin of other parts of the body is usually transplanted to a wound, but this method causes new scars, and if a large area of skin is burned, the normal skin is left almost without transplantation. Graft rejection can occur by using the skin of xenogeneic animals such as cadaveric animals or pigs as a temporary covering for wounds. In this form, artificial skin oils are natural and have a wide medical application prospect in the treatment of burns, scalds and the like, and have received extensive attention and intensive research from researchers in the industry.
The artificial skin is a skin standby product artificially developed in vitro by utilizing the principles and methods of engineering and cell biology and is used for repairing and replacing defective skin tissues. The artificial skin that has been studied for use at present is mainly: (1) artificial skin in the form of film or sponge made of synthetic materials such as polymer plastics, synthetic polypeptide, and artificial fiber; (2) artificial skin made of regenerated protein and biological materials such as animal tissue amnion, peritoneum, fetal membrane, etc.; (3) sheet-like artificial skin made of fully polymerized film. These conventional artificial skins often have tearing in the skin grafting process, or are too weak in adhesion, too weak in strength, too strong in antigenicity and large in irritation, or are not good in permeability, susceptible to infection, or prevented from growing autogenous skin, scars are accumulated, or raw materials are not easily available, the cost is too high, or the process is complicated, the manufacturing is difficult, and the storage is difficult.
Therefore, the development of the material for artificial skin, which has good strength and elasticity, good permeability, no stimulation to the wound surface, strong antibacterial property, excellent stability and safe and convenient use, can be closely attached to the wound surface, meets the market demand and has very important significance.
Disclosure of Invention
In order to overcome the defects in the prior art, the invention aims to provide an artificial skin material and a preparation method thereof. The invention is realized by the following scheme:
an artificial skin material comprises a surface layer and an inner layer, wherein the surface layer and the inner layer are bonded through an adhesive layer; the surface layer is prepared by firstly carrying out polycondensation reaction on 2, 4-dicarboxylthiazole and 1, 3-bis (4-hydroxybutyl) tetramethyldisiloxane to obtain a polycondensate, and then adding alginic acid for end capping; the inner layer is prepared from polycondensate prepared by the polycondensation of 6-amino-6-deoxy-alpha-D-glucopyranosyl 6-amino-6-deoxy-alpha-D-glucopyranoside and furan-2, 5 dicarboxylic acid, collagen and epidermal growth factor.
Preferably, the adhesive layer is made of at least one of polyacrylic acid, polyurethane and polyacrylamide.
Preferably, the preparation method of the surface layer comprises the following steps: adding 2, 4-dicarboxylthiazole and 1, 3-bis (4-hydroxybutyl) tetramethyldisiloxane into a high boiling point solvent, adding dicyclohexylcarbodiimide and 4-dimethylaminopyridine into the solvent, stirring the mixture for 1 to 2 hours under the ice-water bath condition in the atmosphere of nitrogen or inert gas, stirring the mixture for reaction for 18 to 22 hours at the temperature of 160-180 ℃, adding alginic acid, continuing stirring the mixture for reaction for 2 to 3 hours, precipitating the mixture in water after the reaction is finished, washing the product for 5 to 8 times by using dichloromethane, washing the product to be neutral by using water, shearing the product to form a film, and finally placing the film in a vacuum drying oven for drying the film for 15 to 20 hours at the temperature of 70 to 80 ℃ to obtain a surface layer.
Preferably, the mass ratio of the 2, 4-dicarboxylthiazole to the 1, 3-bis (4-hydroxybutyl) tetramethyldisiloxane to the high boiling point solvent to the dicyclohexylcarbodiimide to the 4-dimethylaminopyridine to the alginic acid is 1:1.58 (8-12): 0.4-0.6): 0.2-0.3): 0.1.
Preferably, the high boiling point solvent is selected from one or more of dimethyl sulfoxide, N-dimethylformamide and N-methylpyrrolidone.
Preferably, the inert gas is selected from one of helium, neon and argon.
Preferably, the preparation method of the lining comprises the following steps:
i, dissolving 6-amino-6-deoxy-alpha-D-glucopyranosyl 6-amino-6-deoxy-alpha-D-glucopyranoside, furan-2, 5 dicarboxylic acid, N-diisopropylethylamine and 4-dimethylaminopyridine in dimethyl sulfoxide to form a solution, adding the solution into a reaction kettle, replacing the air in the kettle with nitrogen, reacting for 3-4 hours at 90-100 ℃ under normal pressure, heating to 130 ℃ and 140 ℃ for reaction for 3-5 hours, heating to 230 ℃ and 250 ℃, performing polycondensation reaction for 18-22 hours under 500Pa, cooling to room temperature, adjusting to normal pressure, precipitating in acetone, washing the precipitated polymer with acetone for 3-5 times, drying in a vacuum drying oven at 85-95 ℃ for 18-22 hours, obtaining a polycondensate;
and II, dissolving the polycondensate prepared in the step I in N, N-dimethylformamide, adding collagen, epidermal growth factor, dicyclohexylcarbodiimide and 4-dimethylaminopyridine into the N, N-dimethylformamide, stirring and reacting at 60-80 ℃ for 12-15 hours, then performing rotary evaporation to remove the solvent, washing with water at 30-40 ℃ to be neutral, shearing to form a film, and then placing the film in a vacuum drying oven at 50-60 ℃ for drying for 10-15 hours to obtain the lining.
Preferably, the mass ratio of the 6-amino-6-deoxy-alpha-D-glucopyranosyl-6-amino-6-deoxy-alpha-D-glucopyranoside, furan-2, 5 dicarboxylic acid, N-diisopropylethylamine, 4-dimethylaminopyridine and dimethyl sulfoxide in the step I is 2.3:1 (0.4-0.6) to 0.3 (10-15).
Preferably, the mass ratio of the polycondensate, the N, N-dimethylformamide, the collagen, the epidermal growth factor, the dicyclohexylcarbodiimide and the 4-dimethylaminopyridine in the step II is 1 (10-15): 3-5): 0.1-0.3): 0.4-0.6): 0.3.
Preferably, the preparation method of the artificial skin material comprises the following steps: and (3) sequentially laminating the surface layer, the adhesive layer and the inner layer from top to bottom, and performing compression molding to obtain the artificial skin material.
An artificial skin is prepared from the artificial skin material.
Adopt the produced beneficial effect of above-mentioned technical scheme to lie in:
1) the preparation method of the artificial skin material provided by the invention has the advantages of simple process, easy operation, low dependence on equipment, easily available raw materials and low cost, and is suitable for large-scale production.
2) The artificial skin material provided by the invention overcomes the technical problems that the traditional artificial skin often has tearing, or has poor strength due to poor adhesion, or has too strong antigenicity, large irritation, or poor permeability, is susceptible to infection, or hinders the growth of autogenous skin, scars are tired, or has difficult raw material sources, too high cost, or complicated process, difficult manufacture and difficult storage, and has the advantages of good strength and elasticity, good permeability, capability of closely adhering to a wound surface, no irritation to the wound surface, strong antibacterial performance, excellent stability and safe and convenient use.
3) The surface layer of the artificial skin material provided by the invention is prepared by carrying out polycondensation reaction on 2, 4-dicarboxylthiazole and 1, 3-bis (4-hydroxybutyl) tetramethyldisiloxane to obtain a polycondensate, and then adding alginic acid for end capping, wherein the thiazole structure and the alginic acid structure have synergistic effect, so that the material has excellent bacteria growth inhibition and good biomedical characteristics, and the material can simultaneously keep better skin glossiness and elasticity due to the synergistic effect of the structures.
4) The inner layer of the artificial skin material provided by the invention is made of polycondensate prepared by polycondensation of 6-amino-6-deoxy-alpha-D-glucopyranosyl 6-amino-6-deoxy-alpha-D-glucopyranoside and furan-2, 5 dicarboxylic acid, collagen and epidermal growth factor, has excellent biocompatibility, and is in a three-dimensional network structure through chemical reaction, so that the mechanical property of the material is improved, the added epidermal growth factor is favorable for promoting the growth of new skin, and the biodegradable property of the material is good.
Detailed Description
In order to make the technical solutions of the present invention better understood and make the above features, objects, and advantages of the present invention more comprehensible, the present invention is further described with reference to the following examples. The examples are intended to illustrate the invention only and are not intended to limit the scope of the invention.
The raw materials described in the following examples of the present invention are from Shanghai spring Xin import & export trade company, Inc.
Example 1
An artificial skin material comprises a surface layer and an inner layer, wherein the surface layer and the inner layer are bonded through an adhesive layer; the surface layer is prepared by firstly carrying out polycondensation reaction on 2, 4-dicarboxylthiazole and 1, 3-bis (4-hydroxybutyl) tetramethyldisiloxane to obtain a polycondensate, and then adding alginic acid for end capping; the inner layer is prepared from polycondensate prepared by the polycondensation of 6-amino-6-deoxy-alpha-D-glucopyranosyl 6-amino-6-deoxy-alpha-D-glucopyranoside and furan-2, 5 dicarboxylic acid, collagen and epidermal growth factor.
The adhesive layer is made of polyacrylic acid.
The preparation method of the surface layer comprises the following steps: adding 10g of 2, 4-dicarboxylthiazole and 15.8g of 1, 3-bis (4-hydroxybutyl) tetramethyldisiloxane into 80g of dimethyl sulfoxide, adding 4g of dicyclohexylcarbodiimide and 2g of 4-dimethylaminopyridine into the dimethyl sulfoxide, stirring the mixture for 1 hour under the condition of ice-water bath in the nitrogen atmosphere, stirring the mixture for reaction for 18 hours at 160 ℃, adding 1g of alginic acid, continuing stirring the mixture for reaction for 2 hours, precipitating the mixture in water after the reaction is finished, washing the product for 5 times by using dichloromethane, washing the product to be neutral by using water, shearing the product to form a film, and finally placing the film in a vacuum drying oven for drying for 15 hours at 70 ℃ to obtain a surface layer.
The preparation method of the lining comprises the following steps:
i, dissolving 23g of 6-amino-6-deoxy-alpha-D-glucopyranosyl 6-amino-6-deoxy-alpha-D-glucopyranoside, 10g of furan-2, 5 dicarboxylic acid, 4g of N, N-diisopropylethylamine and 3g of 4-dimethylaminopyridine in 100g of dimethyl sulfoxide to form a solution, adding the solution into a reaction kettle, replacing air in the kettle with nitrogen, reacting at 90 ℃ under normal pressure for 3 hours, heating to 130 ℃ for 3 hours, then heating to 230 ℃, carrying out polycondensation reaction for 18 hours under 500Pa, cooling to room temperature, adjusting to normal pressure, precipitating in acetone, washing the precipitated polymer with acetone for 3 times, and drying in a vacuum drying oven at 85 ℃ for 18 hours to obtain a polycondensate;
II, dissolving 10g of polycondensate prepared in the step I in 100g of N, N-dimethylformamide, adding 30g of collagen, 1g of epidermal growth factor, 4g of dicyclohexylcarbodiimide and 3g of 4-dimethylaminopyridine into the polycondensate, stirring and reacting at 60 ℃ for 12 hours, then performing rotary evaporation to remove the solvent, washing the polycondensate to be neutral by using water at 30 ℃, shearing to form a film, and then placing the film in a vacuum drying oven at 50 ℃ for drying for 10 hours to obtain an inner layer.
The preparation method of the artificial skin material comprises the following steps: and (3) sequentially laminating the surface layer, the adhesive layer and the inner layer from top to bottom, and performing compression molding to obtain the artificial skin material.
An artificial skin is prepared from the artificial skin material.
Example 2
An artificial skin material comprises a surface layer and an inner layer, wherein the surface layer and the inner layer are bonded through an adhesive layer; the surface layer is prepared by firstly carrying out polycondensation reaction on 2, 4-dicarboxylthiazole and 1, 3-bis (4-hydroxybutyl) tetramethyldisiloxane to obtain a polycondensate, and then adding alginic acid for end capping; the inner layer is prepared from polycondensate prepared by the polycondensation of 6-amino-6-deoxy-alpha-D-glucopyranosyl 6-amino-6-deoxy-alpha-D-glucopyranoside and furan-2, 5 dicarboxylic acid, collagen and epidermal growth factor.
The adhesive layer is made of polyurethane.
The preparation method of the surface layer comprises the following steps: adding 10g of 2, 4-dicarboxylthiazole and 15.8g of 1, 3-bis (4-hydroxybutyl) tetramethyldisiloxane into 95g of N, N-dimethylformamide, adding 4.5g of dicyclohexylcarbodiimide and 2.3g of 4-dimethylaminopyridine into the dimethylformamide, stirring for 1.2 hours under the condition of ice-water bath in a helium atmosphere, stirring for reacting for 19 hours at 165 ℃, adding 1g of alginic acid, continuing to stir for reacting for 2.3 hours, precipitating in water after the reaction is finished, washing a product for 6 times by using dichloromethane, washing to be neutral by using water, shearing to form a film, and finally placing the film in a vacuum drying oven for drying for 16 hours at 73 ℃ to obtain a surface layer.
The preparation method of the lining comprises the following steps:
i, dissolving 23g of 6-amino-6-deoxy-alpha-D-glucopyranosyl 6-amino-6-deoxy-alpha-D-glucopyranoside, 10g of furan-2, 5 dicarboxylic acid, 4.5g of N, N-diisopropylethylamine and 3g of 4-dimethylaminopyridine in 115g of dimethyl sulfoxide to form a solution, adding the solution into a reaction kettle, replacing air in the kettle with nitrogen, reacting at 93 ℃ for 3.3 hours under normal pressure, heating to 133 ℃ for 3.5 hours, heating to 235 ℃, carrying out polycondensation reaction for 19 hours under 500Pa, cooling to room temperature, adjusting to normal pressure, precipitating in acetone, washing the precipitated polymer with acetone for 4 times, and drying at 88 ℃ in a vacuum drying oven for 19 hours to obtain a polycondensate;
II, dissolving 10g of polycondensate prepared in the step I in 120g of N, N-dimethylformamide, adding 35g of collagen, 1.5g of epidermal growth factor, 4.5g of dicyclohexylcarbodiimide and 3g of 4-dimethylaminopyridine into the polycondensate, stirring the mixture at 65 ℃ for reacting for 13 hours, then performing rotary evaporation to remove the solvent, washing the mixture to be neutral by using water at 33 ℃, shearing the mixture to form a film, and then placing the film in a vacuum drying oven at 53 ℃ for drying for 12 hours to obtain an inner layer.
The preparation method of the artificial skin material comprises the following steps: and (3) sequentially laminating the surface layer, the adhesive layer and the inner layer from top to bottom, and performing compression molding to obtain the artificial skin material.
An artificial skin is prepared from the artificial skin material.
Example 3
An artificial skin material comprises a surface layer and an inner layer, wherein the surface layer and the inner layer are bonded through an adhesive layer; the surface layer is prepared by firstly carrying out polycondensation reaction on 2, 4-dicarboxylthiazole and 1, 3-bis (4-hydroxybutyl) tetramethyldisiloxane to obtain a polycondensate, and then adding alginic acid for end capping; the inner layer is prepared from polycondensate prepared by the polycondensation of 6-amino-6-deoxy-alpha-D-glucopyranosyl 6-amino-6-deoxy-alpha-D-glucopyranoside and furan-2, 5 dicarboxylic acid, collagen and epidermal growth factor.
The adhesive layer is made of polyacrylamide.
The preparation method of the surface layer comprises the following steps: adding 10g of 2, 4-dicarboxylthiazole and 15.8g of 1, 3-bis (4-hydroxybutyl) tetramethyldisiloxane into 105g of N-methylpyrrolidone, adding 5g of dicyclohexylcarbodiimide and 2.5g of 4-dimethylaminopyridine into the N-methylpyrrolidone, stirring for 1.5 hours under the condition of ice-water bath in the atmosphere of neon, stirring for reaction for 20 hours at 170 ℃, adding 1g of alginic acid, continuously stirring for reaction for 2.5 hours, precipitating in water after the reaction is finished, washing the product for 7 times by using dichloromethane, washing the product to be neutral by using water, shearing to form a film, and finally drying the film in a vacuum drying oven at 75 ℃ for 18 hours to obtain a surface layer.
The preparation method of the lining comprises the following steps:
i, dissolving 23g of 6-amino-6-deoxy-alpha-D-glucopyranosyl 6-amino-6-deoxy-alpha-D-glucopyranoside, 10g of furan-2, 5 dicarboxylic acid, 5g of N, N-diisopropylethylamine and 3g of 4-dimethylaminopyridine in 130g of dimethyl sulfoxide to form a solution, adding the solution into a reaction kettle, replacing air in the kettle with nitrogen, reacting at 96 ℃ for 3.5 hours under normal pressure, then heating to 136 ℃ for 4 hours, then heating to 240 ℃, carrying out polycondensation reaction for 20 hours under 500Pa, then cooling to room temperature, adjusting to normal pressure, precipitating in acetone, washing the precipitated polymer with acetone for 4 times, and then placing in a vacuum drying oven for drying for 20 hours at 90 ℃ to obtain a polycondensate;
II, dissolving 10g of polycondensate prepared in the step I in 135g of N, N-dimethylformamide, adding 40g of collagen, 2g of epidermal growth factor, 5g of dicyclohexylcarbodiimide and 3g of 4-dimethylaminopyridine into the polycondensate, stirring and reacting at 70 ℃ for 13.5 hours, removing the solvent by rotary evaporation, washing to neutrality by using water at 35 ℃, shearing to form a film, and then placing the film in a vacuum drying oven at 56 ℃ for drying for 13 hours to obtain an inner layer.
The preparation method of the artificial skin material comprises the following steps: and (3) sequentially laminating the surface layer, the adhesive layer and the inner layer from top to bottom, and performing compression molding to obtain the artificial skin material.
An artificial skin is prepared from the artificial skin material.
Example 4
An artificial skin material comprises a surface layer and an inner layer, wherein the surface layer and the inner layer are bonded through an adhesive layer; the surface layer is prepared by firstly carrying out polycondensation reaction on 2, 4-dicarboxylthiazole and 1, 3-bis (4-hydroxybutyl) tetramethyldisiloxane to obtain a polycondensate, and then adding alginic acid for end capping; the inner layer is prepared from polycondensate prepared by the polycondensation of 6-amino-6-deoxy-alpha-D-glucopyranosyl 6-amino-6-deoxy-alpha-D-glucopyranoside and furan-2, 5 dicarboxylic acid, collagen and epidermal growth factor.
The adhesive layer is prepared from a mixture of polyacrylic acid, polyurethane and polyacrylamide in a mass ratio of 1:2: 1.
The preparation method of the surface layer comprises the following steps: adding 10g of 2, 4-dicarboxylthiazole and 15.8g of 1, 3-bis (4-hydroxybutyl) tetramethyldisiloxane into 110g of a high-boiling-point solvent, adding 5.5g of dicyclohexylcarbodiimide and 2.8g of 4-dimethylaminopyridine into the solvent, stirring for 1.8 hours under the condition of ice-water bath under the argon atmosphere, stirring for reacting for 21 hours at 175 ℃, adding 1g of alginic acid, continuing to stir for reacting for 2.9 hours, precipitating in water after the reaction is finished, washing the product for 7 times with dichloromethane, washing with water to neutrality, shearing to form a film, and finally drying the film in a vacuum drying oven at 79 ℃ for 19 hours to obtain a surface layer.
The high-boiling-point solvent is a mixture formed by mixing dimethyl sulfoxide, N-dimethylformamide and N-methylpyrrolidone according to the mass ratio of 2:3: 1.
The preparation method of the lining comprises the following steps:
i, dissolving 23g of 6-amino-6-deoxy-alpha-D-glucopyranosyl 6-amino-6-deoxy-alpha-D-glucopyranoside, 10g of furan-2, 5 dicarboxylic acid, 5.8g of N, N-diisopropylethylamine and 3g of 4-dimethylaminopyridine in 145g of dimethyl sulfoxide to form a solution, adding the solution into a reaction kettle, replacing air in the kettle with nitrogen, reacting at 98 ℃ under normal pressure for 3.8 hours, heating to 138 ℃ for 4.8 hours, then heating to 245 ℃, carrying out polycondensation reaction under 500Pa for 21.5 hours, then cooling to room temperature, adjusting to normal pressure, precipitating in acetone, washing the precipitated polymer with acetone for 5 times, and then placing in a vacuum drying oven at 93 ℃ for drying for 21.5 hours to obtain a polycondensate;
II 10g of the polycondensate prepared in the step I is dissolved in 145g of N, N-dimethylformamide, 45g of collagen, 2.8g of epidermal growth factor, 5.8g of dicyclohexylcarbodiimide and 3g of 4-dimethylaminopyridine are added into the polycondensate, the mixture is stirred and reacted at 78 ℃ for 14.5 hours, then the solvent is removed by rotary evaporation, the mixture is washed to be neutral by 39 ℃ water and is sheared into a film, and the film is dried in a vacuum drying oven at 59 ℃ for 14.5 hours to obtain an inner layer.
The preparation method of the artificial skin material comprises the following steps: and (3) sequentially laminating the surface layer, the adhesive layer and the inner layer from top to bottom, and performing compression molding to obtain the artificial skin material.
An artificial skin is prepared from the artificial skin material.
Example 5
An artificial skin material comprises a surface layer and an inner layer, wherein the surface layer and the inner layer are bonded through an adhesive layer; the surface layer is prepared by firstly carrying out polycondensation reaction on 2, 4-dicarboxylthiazole and 1, 3-bis (4-hydroxybutyl) tetramethyldisiloxane to obtain a polycondensate, and then adding alginic acid for end capping; the inner layer is prepared from polycondensate prepared by the polycondensation of 6-amino-6-deoxy-alpha-D-glucopyranosyl 6-amino-6-deoxy-alpha-D-glucopyranoside and furan-2, 5 dicarboxylic acid, collagen and epidermal growth factor.
The adhesive layer is made of polyurethane.
The preparation method of the surface layer comprises the following steps: adding 10g of 2, 4-dicarboxylthiazole and 15.8g of 1, 3-bis (4-hydroxybutyl) tetramethyldisiloxane into 120g of N, N-dimethylformamide, adding 6g of dicyclohexylcarbodiimide and 3g of 4-dimethylaminopyridine into the dimethylformamide, stirring for 2 hours under the condition of ice-water bath in the nitrogen atmosphere, stirring for reaction for 22 hours at 180 ℃, adding 1g of alginic acid, continuing stirring for reaction for 3 hours, precipitating in water after the reaction is finished, washing the product for 8 times with dichloromethane, washing with water until the product is neutral, shearing to form a film, and finally placing the film in a vacuum drying oven to be dried for 20 hours at 80 ℃ to obtain a surface layer.
The preparation method of the lining comprises the following steps:
i, dissolving 23g of 6-amino-6-deoxy-alpha-D-glucopyranosyl 6-amino-6-deoxy-alpha-D-glucopyranoside, 10g of furan-2, 5 dicarboxylic acid, 6g of N, N-diisopropylethylamine and 3g of 4-dimethylaminopyridine in 150g of dimethyl sulfoxide to form a solution, adding the solution into a reaction kettle, replacing the air in the kettle with nitrogen, reacting at 100 ℃ under normal pressure for 4 hours, then heating to 140 ℃ for 5 hours, then heating to 250 ℃, carrying out polycondensation reaction under 500Pa for 22 hours, then cooling to room temperature, adjusting to normal pressure, precipitating in acetone, washing the precipitated polymer with acetone for 5 times, and then placing in a vacuum drying oven for drying at 95 ℃ for 22 hours to obtain a polycondensate;
II, dissolving 10g of polycondensate prepared in the step I in 150g of N, N-dimethylformamide, adding 50g of collagen, 3g of epidermal growth factor, 6g of dicyclohexylcarbodiimide and 3g of 4-dimethylaminopyridine into the polycondensate, stirring the mixture at 80 ℃ for reaction for 15 hours, removing the solvent by rotary evaporation, washing the product to be neutral by using water at 40 ℃, shearing the product to form a film, and then placing the film in a vacuum drying oven at 60 ℃ for drying for 15 hours to obtain an inner layer.
The preparation method of the artificial skin material comprises the following steps: and (3) sequentially laminating the surface layer, the adhesive layer and the inner layer from top to bottom, and performing compression molding to obtain the artificial skin material.
An artificial skin is prepared from the artificial skin material.
Comparative example
The present example provides an artificial skin material, which is prepared according to the preparation method of example 1 of the Chinese patent CN 101716376B.
The artificial skin materials prepared in the above examples 1 to 5 and the general skin material of the comparative example were subjected to the relevant performance tests, and the test results are shown in table 1. The test method is as follows:
(1) skin material surface moisture loss test: cutting the sample skin material into 5cm diameter circles, soaking in 10% glycerol aqueous solution, removing, applying on human skin for 30 min, taking off the sample skin material, and measuring water loss on skin surface with CK Electronic multifunctional skin detector, MPA580 model after 15 min.
(2) And (3) detecting the antibacterial property of the skin material: selecting skin material of 10 square centimeters, culturing in human serum culture medium, simulating human body environment, and culturing Staphylococcus aureus and hemolytic streptococcus to 10% by conventional culture method in the field8CFU/mL, then add 1 drop to the skin material surface, 37 degrees C were cultured for 2 days, observed results.
(3) Mechanical properties of skin materials: the test was carried out using the test method GB/T1701-2001.
TABLE 1
As can be seen from the above table, the artificial skin material disclosed in the embodiments of the present invention has more excellent mechanical properties, antibacterial properties, and moisture retention properties than the artificial skin material in the prior art.
The foregoing shows and describes the general principles, essential features, and advantages of the invention. It will be understood by those skilled in the art that the present invention is not limited to the embodiments described above, which are merely illustrative of the principles of the invention, but that various changes and modifications may be made without departing from the spirit and scope of the invention, which fall within the scope of the invention as claimed. The scope of the invention is defined by the appended claims and equivalents thereof.
Claims (8)
1. The antibacterial and nonirritating medical artificial skin is characterized by being prepared from an artificial skin material comprising a surface layer and an inner layer, wherein the surface layer is prepared by carrying out polycondensation reaction on 2, 4-dicarboxylthiazole and 1, 3-bis (4-hydroxybutyl) tetramethyldisiloxane to obtain a polycondensate and then adding alginic acid for end capping; the inner layer is prepared from polycondensate prepared by the polycondensation of 6-amino-6-deoxy-alpha-D-glucopyranosyl 6-amino-6-deoxy-alpha-D-glucopyranoside and furan-2, 5 dicarboxylic acid, collagen and epidermal growth factor.
2. The artificial skin according to claim 1, wherein the top layer and the inner layer are bonded by an adhesive layer, wherein the adhesive layer is made of at least one of polyacrylic acid, polyurethane, and polyacrylamide.
3. The artificial skin for medical use of claim 1, wherein the top sheet is prepared by a method comprising the steps of: adding 2, 4-dicarboxylthiazole and 1, 3-bis (4-hydroxybutyl) tetramethyldisiloxane into a high boiling point solvent, adding dicyclohexylcarbodiimide and 4-dimethylaminopyridine into the solvent, stirring for 1-2 hours under the condition of ice-water bath in the atmosphere of nitrogen or inert gas, stirring and reacting for 18-22 hours at the temperature of 160-180 ℃, adding alginic acid, continuously stirring and reacting for 2-3 hours, after the reaction is finished, precipitating in water, washing the product with dichloromethane for 5-8 times, washing with water to neutrality, cutting to form a film, finally placing the film in a vacuum drying oven to be dried for 15-20 hours at the temperature of 70-80 ℃ to obtain a surface layer, wherein the high boiling point solvent is selected from one or more of dimethyl sulfoxide, N-dimethylformamide and N-methylpyrrolidone.
4. The antibacterial and non-irritant medical artificial skin as claimed in claim 3, wherein the mass ratio of the 2, 4-dicarboxythiazole, the 1, 3-bis (4-hydroxybutyl) tetramethyldisiloxane, the high boiling point solvent, the dicyclohexylcarbodiimide, the 4-dimethylaminopyridine and the alginic acid is 1:1.58 (8-12): 0.4-0.6): 0.2-0.3): 0.1.
5. The artificial skin for medical use of claim 3, wherein said inert gas is selected from the group consisting of helium, neon, and argon.
6. The artificial skin for medical use of claim 1, wherein the inner layer is prepared by a method comprising the steps of:
i, dissolving 6-amino-6-deoxy-alpha-D-glucopyranosyl 6-amino-6-deoxy-alpha-D-glucopyranoside, furan-2, 5 dicarboxylic acid, N-diisopropylethylamine and 4-dimethylaminopyridine in dimethyl sulfoxide to form a solution, adding the solution into a reaction kettle, replacing the air in the kettle with nitrogen, reacting for 3-4 hours at 90-100 ℃ under normal pressure, heating to 130 ℃ and 140 ℃ for reaction for 3-5 hours, heating to 230 ℃ and 250 ℃, performing polycondensation reaction for 18-22 hours under 500Pa, cooling to room temperature, adjusting to normal pressure, precipitating in acetone, washing the precipitated polymer with acetone for 3-5 times, drying in a vacuum drying oven at 85-95 ℃ for 18-22 hours, obtaining a polycondensate;
and II, dissolving the polycondensate prepared in the step I in N, N-dimethylformamide, adding collagen, epidermal growth factor, dicyclohexylcarbodiimide and 4-dimethylaminopyridine into the N, N-dimethylformamide, stirring and reacting at 60-80 ℃ for 12-15 hours, then performing rotary evaporation to remove the solvent, washing with water at 30-40 ℃ to be neutral, shearing to form a film, and then placing the film in a vacuum drying oven at 50-60 ℃ for drying for 10-15 hours to obtain the lining.
7. The antibacterial and nonirritating medical artificial skin as claimed in claim 6, wherein the mass ratio of the 6-amino-6-deoxy-alpha-D-glucopyranosyl 6-amino-6-deoxy-alpha-D-glucopyranoside, furan-2, 5 dicarboxylic acid, N-diisopropylethylamine, 4-dimethylaminopyridine and dimethyl sulfoxide in step I is 2.3:1 (0.4-0.6) to 0.3 (10-15).
8. The antibacterial and non-irritant medical artificial skin as claimed in claim 6, wherein the mass ratio of the polycondensate, the N, N-dimethylformamide, the collagen, the epidermal growth factor, the dicyclohexylcarbodiimide and the 4-dimethylaminopyridine in the step II is 1 (10-15): 3-5): 0.1-0.3): 0.4-0.6): 0.3.
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| CN201811111438.1A CN109045358A (en) | 2018-09-23 | 2018-09-23 | A kind of artificial skin material |
| CN202011441305.8A CN112472874A (en) | 2018-09-23 | 2018-09-23 | Antibacterial and non-irritant medical artificial skin |
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| CN202011441305.8A Withdrawn CN112472874A (en) | 2018-09-23 | 2018-09-23 | Antibacterial and non-irritant medical artificial skin |
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| CN109731123A (en) * | 2019-02-25 | 2019-05-10 | 湖南博隽生物医药有限公司 | A kind of medical nursing anti-infective material and preparation method thereof |
| CN112245646A (en) * | 2020-10-09 | 2021-01-22 | 朱荣艳 | Skin care material and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| JPS5980602A (en) * | 1982-11-01 | 1984-05-10 | Toagosei Chem Ind Co Ltd | Mildewproofing composition |
| CN1194777C (en) * | 2000-10-11 | 2005-03-30 | 山东绿叶制药股份有限公司 | Artificial skin and its prepn and use |
| CN101716376B (en) * | 2009-11-20 | 2014-10-22 | 深圳齐康医疗器械有限公司 | Growth factor slow-release type double-layered artificial skin |
| CN103374208B (en) * | 2012-04-24 | 2015-11-18 | 苏州纳晶医药技术有限公司 | A kind of can the polymer materials and preparation method thereof of gradient degradation |
| CN103948960B (en) * | 2014-05-20 | 2016-01-13 | 四川大学 | A kind of containing nanometer silver porous silicone rubber/polyurethane double-layered artificial skin and preparation method thereof |
| CN105056279A (en) * | 2015-08-12 | 2015-11-18 | 杭州承前生物科技有限公司 | Double-layer polyurethane-based collagen-compounded dressing |
| CN106853263A (en) * | 2017-02-16 | 2017-06-16 | 深圳齐康医疗器械有限公司 | A kind of artificial skin and preparation method thereof |
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- 2018-09-23 CN CN201811111438.1A patent/CN109045358A/en not_active Withdrawn
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| CN109045358A (en) | 2018-12-21 |
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