CN109939256B - Asymmetric skin dressing and manufacturing method thereof - Google Patents
Asymmetric skin dressing and manufacturing method thereof Download PDFInfo
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- CN109939256B CN109939256B CN201910255204.2A CN201910255204A CN109939256B CN 109939256 B CN109939256 B CN 109939256B CN 201910255204 A CN201910255204 A CN 201910255204A CN 109939256 B CN109939256 B CN 109939256B
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Abstract
The invention discloses an asymmetric skin dressing and a preparation method thereof, wherein the asymmetric dry skin dressing or the wet skin dressing is obtained by preparing a liquid dressing, pouring the liquid dressing into a container for casting to form a film, then adding a thin layer of dimethyl sulfoxide on the film, freezing at low temperature, and adding a cross-linking agent for soaking. The invention can guide the regeneration of the tissue of the wound part by utilizing the loose layer of the asymmetric dressing, and the compact layer can prevent the invasion of external stimulus factors. The dry dressing does not contain liquid, can absorb certain seepage, and can be applied to exudative wounds; the wet dressing can use various cross-linking agents, redundant cross-linking agents can be removed to the maximum degree in the later stage, the safety is higher, and the dressing is softer and more flexible. The dense layer can be hardened by dimethyl sulfoxide to effectively prevent the invasion of external stimulus, and simultaneously, the dense layer can be permeable to air to block the external stimulus on the basis of guiding the tissue regeneration.
Description
Technical Field
The invention relates to the fields of high polymer materials, dressing compositions and preparation methods thereof, in particular to an asymmetric skin dressing and a preparation method thereof.
Background
The ideal skin dressing has the characteristics of preventing the wound surface from drying, maintaining a moist, clean and warm environment, absorbing excessive secretion, being breathable, protecting the wound surface from being infected by external harmful substances, releasing no fibers or particles, keeping the shape of the wound, causing light pain during replacement, having high cost performance and the like.
Traditional dressing lower floor is loose sponge appearance loose layer, uses polyurethane as the upper strata, plays the lower floor and absorbs the sepage, and the guide tissue regeneration, external stimulus is kept apart on the upper strata, prevents the microorganism invasion. The invention relates to an asymmetric skin dressing, which has a compact upper layer, can prevent the invasion of microorganisms while ensuring air permeability, and can effectively absorb seepage and guide tissue regeneration when the lower layer is loose. The raw material of the artificial skin can be composed of one or more of natural high molecular material gelatin, collagen, sodium alginate, carboxymethyl chitosan, chondroitin sulfate, sodium hyaluronate and chitosan. One or more of calcium chloride, 1, 4-butanediol diglycidyl ether or glutaraldehyde is used. The dressing is simple to manufacture, and dressings with different thicknesses can be prepared according to requirements.
Disclosure of Invention
The purpose of the invention is as follows: the invention aims to provide a preparation method of an asymmetric skin dressing with a compact upper layer and a loose lower layer, and also aims to provide a dry skin dressing and a wet skin dressing prepared by the method.
The technical scheme is as follows: in order to achieve the above object, the method for manufacturing an asymmetric skin dressing of the present invention specifically comprises: preparing a liquid dressing, wherein the liquid dressing is selected from any one or combination of more of gelatin, collagen, sodium alginate, carboxymethyl chitosan, chondroitin sulfate, sodium hyaluronate and chitosan; pouring the liquid dressing into a container, casting to form a film, adding a thin layer of dimethyl sulfoxide on the film, freezing at low temperature, adding a cross-linking agent, soaking, and drying
a) Washing with deionized water to obtain asymmetric wet skin dressing with compact upper layer and loose lower layer, or
b) The asymmetric dry skin dressing with compact upper layer and loose lower layer is obtained by low-temperature drying.
The method provided by the invention can obtain asymmetric dressings with dry and wet properties, so that the asymmetric dressings are suitable for different purposes. The dressing has compact upper layer, can isolate external stimulation and prevent microorganism invasion; the lower layer is loose, and can effectively absorb seepage and guide tissue regeneration.
The liquid dressing of the invention includes but is not limited to any one or combination of more of gelatin, collagen, sodium alginate, carboxymethyl chitosan, chondroitin sulfate, sodium hyaluronate and chitosan, and pore-forming agent and/or pH regulator can be added on the basis of the liquid dressing. Preferably, the liquid dressing at least contains 1% -5% of carboxymethyl chitosan, which is used as a main component of the compact layer, and dimethyl sulfoxide slowly permeates into the polymer solution under the low-temperature condition to absorb part of water in the polymer solution and simultaneously prevent large ice crystals on a contact surface from forming, so that the contact surface of the dimethyl sulfoxide and the polymer material is compact.
The pore-foaming agent includes but is not limited to sodium chloride and potassium chloride solutions with different proportions. Because the low-temperature salt solution is crystallized, air holes are left after the salt solution is removed in the subsequent cleaning process, and the penetrating air holes can be formed in an auxiliary mode. The pH regulator includes but is not limited to any one or combination of lactic acid, acetic acid, hydrochloric acid, sodium hydroxide, potassium hydroxide and triethanolamine, and is preferably selected to regulate pH to 4-8.
The concentration of dimethyl sulfoxide is 50% -100%, and pure dimethyl sulfoxide is the best. The less the water content, the more effective it is in preventing the formation of large ice crystals. The amount of dimethyl sulfoxide added is based on the amount of the polymer casting film which can be covered.
Further, the low-temperature freezing is carried out for 3-5 hours under the environment of minus 30 ℃ to minus 100 ℃.
Further, the cross-linking agent comprises one or more of calcium chloride, 1, 4-butanediol diglycidyl ether and glutaraldehyde.
Further, the cross-linking agent is a mixed solution of 5% of calcium chloride and 1% of 1, 4-butanediol diglycidyl ether.
The dressing prepared by singly using the calcium chloride is connected by ionic bonds, and the prepared dressing has poor relative mechanical property. The 1, 4-butanediol diglycidyl ether or glutaraldehyde is added to increase covalent bond connection, and the prepared dressing has good mechanical property and higher toughness.
Further, the crosslinker was added and soaked at 4 ℃ for 24 hours.
An asymmetric moist skin dressing or an asymmetric dry skin dressing is prepared as described above. The asymmetric skin dressing is 0.5-1.2mm thick. The asymmetric skin dressing has a loose lower layer and a pore diameter of 50-200 mu m. The prepared dry dressing is slightly shrunk in the freeze-drying process, so that the dry dressing prepared by the same mass and volume is slightly thinner than the wet dressing.
Has the advantages that: compared with the traditional dressing, the loose layer of the asymmetric dressing can guide the tissue regeneration of the wound site, and the dense layer can prevent the invasion of external stimulation factors (such as microorganisms). The dry dressing does not contain liquid, can absorb certain seepage, and can be applied to exudative wounds; the wet dressing can use various cross-linking agents, redundant cross-linking agents can be removed to the maximum degree in the later stage, the safety is higher, and the dressing is softer and more flexible. The dense layer can be effectively prevented from invasion of external stimulation factors (such as microorganisms) through dimethyl sulfoxide hardening, and simultaneously, the dense layer can be permeable to air and can block external stimulation on the basis of guiding tissue regeneration.
Detailed Description
The present invention is further illustrated by the following specific examples. In the various embodiments of the present invention, the solid component is a mass/volume percentage and the liquid component is a volume/volume percentage, unless otherwise specified.
Example 1
Preparing a liquid dressing A: deionized water is used for dissolving 3% of carboxymethyl chitosan, 5% of chondroitin sulfate and 0.5% of sodium alginate to prepare a mixed solution. Then 8ml of liquid dressing is poured into a 90mm culture dish, cast into a film, added with 5ml of dimethyl sulfoxide, placed in a refrigerator at minus 80 ℃, frozen for 4 hours, taken out, filled with 1 percent of glutaraldehyde in the culture dish and placed for 24 hours at 4 ℃.
Then the dressing is washed clean by deionized water to obtain the dressing with the thickness of about 0.5mm, the upper layer is compact and the lower layer is loose. The dressing is a wet dressing, and can be used for wound surface to prevent bacterial invasion and guide tissue regeneration.
Example 2
Preparing a liquid dressing B: deionized water was used to dissolve 4% carboxymethyl chitosan, 0.2% sodium hyaluronate and 2% gelatin to prepare a mixed solution. Then 15ml of the above liquid was poured into a 90mm petri dish, and cast into a film, and 7ml of dimethyl sulfoxide was added. Freezing at-80 deg.C for 5 hr, taking out, adding 20ml of 5% calcium chloride solution, and standing at 4 deg.C for 24 hr.
Discarding the supernatant, and freezing at-30 deg.C for 4 h. Freeze drying to obtain dried skin dressing with dense upper layer and loose lower layer of thickness of 0.8 mm. The compact layer of the dressing can be used for invading tissue stimulating substances, and the loose layer is in contact with the wound surface, so that the dressing can absorb the seepage of the wound surface and play a role in guiding tissue regeneration.
Example 3
Preparing a liquid dressing C: deionized water is used for preparing a solution with the concentration of collagen of 5 percent, chondroitin sulfate of 5 percent and sodium alginate of 2 percent. Pouring 20ml of the liquid into a 90mm culture dish, carrying out tape casting to form a film, adding 5ml of dimethyl sulfoxide, placing the film in a refrigerator at the temperature of 50 ℃ below zero, freezing for 4 hours, taking out the film, adding a mixed solution of 5% of full calcium chloride and 1% of 1, 4-butanediol diglycidyl ether into the culture dish, and placing the mixture for 24 hours at the temperature of 4 ℃.
And (5) washing and soaking for 72h by flowing deionized water to obtain the dressing with the thickness of about 1mm, compact upper layer and loose lower layer. The dressing is a wet dressing, and can be used for wound surface to prevent bacterial invasion and guide tissue regeneration.
Example 4
Preparing a liquid dressing D: deionized water is used for dissolving 3% of carboxymethyl chitosan, 5% of chondroitin sulfate and 3% of sodium chloride to prepare a mixed solution. Deionized water was added with 5% chitosan, the pH was adjusted to acidic with lactic acid, and stirred to a colorless or yellowish viscous liquid. Then 8ml carboxymethyl chitosan-chondroitin sulfate solution is poured into a 90mm culture dish, and the cast film is placed in a refrigerator at minus 80 ℃ for 2 h. Taking out, adding 4ml chitosan solution, spreading the whole culture medium, adding 5ml dimethyl sulfoxide, placing in-80 deg.C refrigerator, and freezing for 4 hr. The petri dish was filled with 5% calcium chloride solution and left at 4 ℃ for 24 h.
And washing with deionized water to obtain dressing with thickness of about 1.2mm, dense upper layer and loose lower layer (pore size of about 50-200 μm). The dressing is a wet dressing, the upper layer is a dense chitosan layer, and the dense chitosan layer can play a certain waterproof role because the dense chitosan layer is insoluble in neutral and alkaline solutions, and can prevent bacteria from invading because the chitosan has the function of inhibiting the growth of microorganisms; the loose layer is distributed with macropores with different pore diameters of 50-200 μm, and micropores are arranged between the macropores. The macropores can guide proliferation and growth of fibroblasts, and the micropores can not pass through cells but can exchange substances.
Claims (9)
1. A method for manufacturing an asymmetric skin dressing, which is characterized in that: preparing a liquid dressing, wherein the liquid dressing is selected from any one or combination of more of gelatin, collagen, sodium alginate, carboxymethyl chitosan, chondroitin sulfate, sodium hyaluronate and chitosan; pouring the liquid dressing into a container to form a high-molecular casting film by casting, adding dimethyl sulfoxide on the high-molecular casting film, covering the high-molecular casting film with the dimethyl sulfoxide, freezing at low temperature, adding a cross-linking agent for soaking, and then adding the dimethyl sulfoxide into the high-molecular casting film
a) Washing with deionized water to obtain asymmetric wet skin dressing with compact upper layer and loose lower layer, or
b) The asymmetric dry skin dressing with compact upper layer and loose lower layer is obtained by low-temperature drying.
2. The method of making an asymmetric skin dressing as claimed in claim 1, wherein: the low-temperature freezing is performed for 3 to 5 hours at the temperature of between 30 ℃ below zero and 100 ℃ below zero.
3. The method of making an asymmetric skin dressing as claimed in claim 1, wherein: the cross-linking agent comprises one or more of calcium chloride, 1, 4-butanediol diglycidyl ether and glutaraldehyde.
4. A method of making an asymmetric skin dressing as claimed in claim 3, wherein: the cross-linking agent is a mixed solution of 5% of calcium chloride and 1% of 1, 4-butanediol diglycidyl ether.
5. The method of claim 4, wherein the asymmetric skin dressing comprises: the crosslinker was added and soaked at 4 ℃ for 24 hours.
6. The method of claim 5, wherein the asymmetric skin dressing comprises: the asymmetric skin dressing is 0.5-1.2mm thick.
7. The method of claim 5, wherein the asymmetric skin dressing comprises: the asymmetric skin dressing has a loose lower layer and a pore diameter of 50-200 mu m.
8. The method of making an asymmetric skin dressing as claimed in claim 1, wherein: the liquid dressing also comprises a pore-foaming agent and a pH regulator.
9. An asymmetric moist skin dressing or an asymmetric dry skin dressing prepared according to the method of claim 1.
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