CN113350568A - Biocompatible polymer dressing based on gelatin - Google Patents

Abstract

According to the invention, aiming at chronic wound surfaces which are difficult to heal, a natural polysaccharide material is subjected to oxidation modification to obtain a polysaccharide crosslinking precursor, the polysaccharide crosslinking precursor can be condensed with gelatin through Schiff base of aldehyde group and amino group under the condition of not adding a small molecular crosslinking agent to obtain a composite biological material, and the composite biological material is subjected to freeze drying and crushing to obtain the dressing which can be stably stored for a long time. Before use, the dressing can be re-dissolved by using a biocompatible sterile solution, and the liquid dressing with uniform texture can be obtained.

Description

Biocompatible polymer dressing based on gelatin

Technical Field

The invention belongs to the fields of biomedicine and medical cosmetology, and particularly relates to an antioxidant biocompatible polymer dressing and application of the dressing in the fields of biomedicine and medical cosmetology.

Background

In the past decades, biocompatible polymers have been the focus of research and advanced in the biomedical and cosmetology fields, and several representative biocompatible polymers have served as a key material basis.

Gelatin is another biocompatible polymer material which has attracted much attention in recent years, and is widely used as a multifunctional natural degradable biopolymer in various fields such as industry, food, medical treatment, cosmetics and the like. Gelatin is a natural product obtained by partially denaturing or chemically hydrolyzing collagen, and the traditional gelatin extraction raw materials mainly comprise skin, bone and tendon of terrestrial mammals (pigs and cattle). Collagen used for preparing gelatin is a protein obtained by extracting raw gelatin from connective tissues of animals including bones, cartilages, skins, tendons, and the like. Gelatin and collagen proteins extracted from animal tissues have approximately the same amino acid composition and are chemically very similar. The gelatin has excellent physical and chemical properties, such as strong hydrophilicity, jelly forming capability, high side chain gene reaction activity, convenience for chemical modification grafting and the like. Because of these advantages, gelatin is widely used in various fields such as food, medicine, cosmetics, and printing industries. Meanwhile, the gelatin has wide sources, low price and good biocompatibility, and is one of the best choices for preparing dressing materials. In addition, modification studies such as chemical modification of gelatin have been reported in recent years.

Hyaluronic Acid (HA) is a linear, non-branched, macromolecular acidic mucopolysaccharide polymer composed of repeated alternate linkages of disaccharides, and the repeating units of Hyaluronic acid molecules are the following two small molecules: β (1, 4) -N-acetyl-D-glucosamine and β (1, 3) -D-glucuronic acid. HA is a non-sulfated glycosaminoglycan. The average molecular weight of HA varies from 200kDa to 10MDa, with the most common size ranging from 2.0MDa to 5.0 MDa. More than 50% of hyaluronic acid is present in skin, lungs and intestines. In addition, it is also present in interstitial tissues such as synovial fluid of joints, cartilage, umbilical cord, and blood vessel wall. Hyaluronic acid synthesized in the human body mainly plays physiological functions of lubrication and buffer action, filling agent and diffusion barrier, free radical removal and the like. Hyaluronic acid products currently used in the market can be extracted from animal tissues (such as cockscomb, vitreous eye, cerebral cartilage, joint fluid) and also fermented from bacteria (such as streptococcus, pseudomonas aeruginosa, etc.).

In recent years, with the intensive research on the functions of HA, HA HAs been widely used in the medical field, such as in the preparation of drug delivery systems and in the treatment of orthopedic and ophthalmic diseases, the prevention of post-operative adhesions, and soft tissue repair, and HAs become a research hotspot in the field of tissue engineering. The natural HA which is easy to degrade can obtain better physical stability and mechanical strength through chemical modification. Chemical crosslinking of HA is typically accomplished by intramolecular crosslinking of HA by small molecule crosslinkers or by post-chemical modification of HA for crosslinking. HA hydrogels obtained by chemical crosslinking have been widely used in the field of tissue engineering. However, many chemical methods for preparing HA hydrogels have various limitations and safety hazards, such as preparation of gel using toxic small molecule cross-linking agents, low efficiency of chemical modification of HA, difficult operation of gel preparation, and the like. Therefore, it is one of the approaches to solve the existing problems to develop a novel HA material with a better crosslinking mechanism or to develop a composite material of HA and other biocompatible polymer compounds.

Chondroitin sulfate is one of the components of connective tissue matrix in organisms, and the action mechanism of chondroitin sulfate is probably related to the inhibition of phosphodiesterase activity, the increase of adenosine cyclophosphate content and the activation of lipolytic enzyme, can promote peripheral circulation and has the function of regulating cell growth. Chondroitin sulfate is a type of glycosaminoglycan, and is a polysaccharide composed of repeating disaccharide units in which D-glucuronic acid and N-acetylgalactosamine are linked by β -1, 4-glycosidic bonds, and is sulfated at the C-4 or C-6 hydroxyl group of N-acetylgalactosamine. Chondroitin sulfate is abundantly present in animal cartilage.

Chronic skin wounds continue to be a problem in clinical medicine, affecting all ages from infants to the elderly, placing a tremendous burden on patients and society. Taking a diabetic ulcer as an example, the 2015 international union for diabetes reports showed that approximately 2600 million diabetic patients develop ulcers worldwide each year, with approximately 20% of patients progressing to amputation and five-year mortality reaching 70% after amputation. The conventional clinical treatment means of the chronic wound has various defects, such as poor curative effect of the traditional operation, formation of additional wound, great pain of patients, high cost of emerging products and the like. The medical dressing can replace the defected skin to form a temporary barrier in wound healing, thereby avoiding wound infection and being beneficial to wound healing. With the development of tissue engineering, various artificial tissues and biomaterials are implanted into the body to repair or replace the structure and function of the defective tissue. However, such commercial products still have the defects of complex process, low safety, complex operation, high cost, poor curative effect and the like. The injectable material has the characteristics of easiness in operation, easiness in filling, easiness in mixing cells or medicines and the like, and the current commercialized products have the characteristics of complex process, low material purity, toxic substance residue and complicated purification process, and are not easy to effectively combine with the cells, the medicines and the like for application.

Traditional hydrocolloid dressings are a class of hydrophilic cross-linked polymeric materials. As an important wound dressing, the hydrocolloid dressing has the function of providing a wet healing environment for the wound. Moreover, the hydrocolloid dressing can prevent the loss of body fluid caused by the loss of wound skin. The application range of the traditional Chinese medicine is gradually expanded from the initial application of the traditional Chinese medicine for treating simple pressure sore, to the treatment of various wound surfaces such as diabetic foot ulcer, phlebitis, skin soft tissue defect and the like. The material has higher degree of fitting with the skin around the wound surface, and the comfort level of a patient is obviously higher than that of common gauze dressing. The hydrocolloid dressing can absorb exudate of the wound surface while maintaining the moisture of the wound surface, and has the effect of eliminating blood stasis and swelling.

However, most of the hydrocolloid dressings in the market are synthetic materials or non-biodegradable carboxymethyl cellulose materials. Synthetic materials typically include PEG hydrocolloid dressings and silane hydrocolloid dressings. Although both of these materials are biologically inert, immune rejection by the organism can be avoided. But also limited by the biological inertia of the material, the synthetic hydrocolloid dressing cannot provide good support for the migration of wound cells, and the promotion effect on wound healing is far lower than that of the natural biological material with biological activity. Therefore, the development of new bio-based wound dressings would yield good social benefits and a wide market place.

Disclosure of Invention

According to the invention, aiming at chronic wound surfaces which are difficult to heal, a natural polysaccharide material is subjected to oxidation modification to obtain a polysaccharide crosslinking precursor, the polysaccharide crosslinking precursor can be condensed with gelatin through Schiff base of aldehyde group and amino group under the condition of not adding a small molecular crosslinking agent to obtain a composite biological material, and the composite biological material is subjected to freeze drying and crushing to obtain the dressing which can be stably stored for a long time. Before use, the dressing can be re-dissolved by using a biocompatible sterile solution, and the liquid dressing with uniform texture can be obtained. Because the gelatin and the natural polysaccharide have excellent biological activity and biodegradability, the dressing of the invention not only can promote the healing of chronic wound, but also has slow release effect on the composite biological active substance, can promote cell proliferation and has good biocompatibility.

According to one aspect of the present invention, there is provided a biocompatible polymer dressing based on gelatin, which is prepared by a method comprising the steps of:

(1) dissolving polysaccharide in water to obtain polysaccharide solution, adding sodium periodate to oxidize polysaccharide, adding alcohol to terminate polysaccharide oxidation reaction, and dialyzing to obtain oxidized polysaccharide solution;

(2) dissolving gelatin in acid-containing water to obtain gelatin solution, adding oxidized polysaccharide solution dropwise into the gelatin solution, stirring for reaction until uniform solution is obtained, adjusting pH of the obtained solution to 6-8 if necessary, and drying to remove water to obtain solid dressing.

Preferably, the method further comprises the following steps: (3) and crushing the obtained solid dressing to obtain the powder dressing.

Preferably, the method further comprises the following steps: (4) and re-dissolving the obtained powder dressing with a biocompatible sterile solution to obtain the liquid dressing. The liquid dressing of the present invention is in the form of a hydrogel. According to the invention, the liquid dressing can be directly applied to the wound surface, and can be used for fully filling wound cavities in smearing mode for cavity wounds, latent wound surfaces and other parts which are difficult to fill the wound cavities, and can achieve the effects of complete filling and no dead cavity by injecting the liquid dressing. It will be appreciated by those skilled in the art that the liquid dressing of the present invention may also be applied to conventional dressings such as gauze.

It will be appreciated by those skilled in the art that in reconstituting a powder dressing, a luer fitting may be used to connect a device, e.g., a syringe, containing the powder dressing to a device, e.g., a syringe, containing a sterile biocompatible solution, such that the powder dressing and the sterile biocompatible solution are thoroughly mixed to provide a hydrogel-like liquid dressing. Generally, the luer used in the present invention is a luer that meets the requirements of medical devices.

Preferably, the polysaccharide is hyaluronic acid, chondroitin sulfate, starch and/or carboxymethyl cellulose. Preferably, the hyaluronic acid has a weight average molecular weight of 3kDa-2MDa, preferably 400kDa-1 MDa; the weight average molecular weight of the chondroitin sulfate is 10kDa-300 kDa; the weight average molecular weight of the starch is 10kDa-100 kDa; the weight average molecular weight of the carboxymethyl cellulose is 10kDa to 1MDa, preferably 10kDa to 400 kDa.

Preferably, in step (1), the concentration (weight/volume) of the polysaccharide solution is 0.1% to 15.0%.

Preferably, in step (1), the ratio of the molar amount of sodium periodate to the molar amount of units of polysaccharide is from 4: 1 to 1: 10.

Preferably, in step (1), the oxidation reaction is carried out for 2 to 48 hours at room temperature with the exclusion of light.

Preferably, in step (1), the alcohol is ethylene glycol, glycerol, mercaptoethanol, and/or ethylene glycol, etc. Preferably, the alcohol is used in an amount of 1.0-4.0mL per 1.07 g of sodium periodate used.

Preferably, in step (2), the acid is acetic acid, hydrochloric acid, propionic acid, formic acid, sulfuric acid, phosphoric acid, or the like. Preferably, the concentration of the acid is from 0.01mol/L to 1.0 mol/L.

Preferably, in step (2), the concentration (weight/volume) of the gelatin solution is 0.1% to 20%.

Preferably, in step (2), the weight ratio of oxidized polysaccharide to gelatin is 1: 99 to 95: 5, preferably 5: 95 to 50: 50, more preferably 8: 92 to 20: 80.

It will be appreciated by those skilled in the art that in step (2), the pH is adjusted using pH adjusting agents commonly used in the art, for example, a hydrochloric acid solution or a sodium hydroxide solution, for example, a 1M hydrochloric acid solution or a 1M sodium hydroxide solution.

It will be appreciated by those skilled in the art that in step (2), moisture is removed using drying methods commonly used in the art. Preferably, freeze drying followed by vacuum drying at 100-.

Preferably, in step (4), the biocompatible sterile solution is physiological saline for injection or glucose solution for injection.

Preferably, in step (4), the biocompatible sterile solution further contains an active substance for promoting wound healing, such as Platelet Rich Plasma (PRP), various growth factors, drugs, stem cells, and the like.

According to another aspect of the invention, there is provided a method of treating a wound by applying a liquid dressing of the invention to the wound surface.

According to another aspect of the invention, the liquid dressing of the invention can be used in a manner of injection administration when a cavity type wound is encountered in clinic.

According to another aspect of the invention, the invention provides the use of the above-described dressing in the biomedical and cosmetology fields. In particular to application in preparing a dressing for treating wounds.

The liquid dressing has uniform and fine texture, and the good biological activity of the liquid dressing can induce cells around the wound surface to migrate into the wound surface, so that the neogenetic tissue can penetrate through the dressing, and the wound surface is stably healed. In addition, the cross-linking precursor material is gelatin and natural polysaccharide, so the liquid dressing can be gradually metabolized and absorbed by tissues along with the gradual healing of the wound surface. Therefore, aiming at the nursing process of the chronic wound surface which is difficult to heal, the use of the material can greatly reduce the dressing change frequency of the wound, and the clinical work burden of medical care workers can be greatly reduced while the pain of patients and the medical expenses are reduced.

The dressing of the invention takes gelatin as a main framework and is added with other biocompatible polymers to realize the effects of promoting and accelerating the healing of various acute and chronic wounds of a human body, in particular to chronic wounds of skin, and the dressing comprises but is not limited to: pressure sores, venous ulcers, diabetic feet, and the like. The composition generally exists in the form of powder, the powder can be redissolved under the action of a proper physiological compatible sterile solution, and the hydrogel-shaped liquid dressing formed after redissolution has the functions of promoting the healing of chronic wounds on the skin, has the characteristic of resisting oxidation, and can effectively reduce active oxygen components and oxidative stress reactions of wound surfaces so as to promote the healing of the wounds.

The liquid dressing has the advantage that the liquid dressing can be better combined with irregular wound surfaces under test conditions and the biological film forming property on the body surface skin. The daily storage form of the product is powder, which is beneficial to the long-term stable storage of the product and the biocompatible high molecular components in the product, and the condition of deterioration or titer reduction caused by hydrolysis can not occur.

In addition, the invention selects gelatin and oxidized natural polysaccharide as crosslinking precursors, and does not need to add micromolecular crosslinking agent; the natural polysaccharide material does not need to be freeze-dried after functional modification, and the cross-linking reaction is carried out in a liquid form, so that the production cost is saved; the re-dissolving process of the material is realized through a luer connector, and the design is convenient for forming the content slow-release dressing by combining stem cells, growth factors, medicaments, PRP and the like.

Drawings

FIG. 1 shows the healing of wound on the back of SD rat in the animal skin full-thickness defect curative effect test of example 6

Detailed Description

The invention will be further illustrated with reference to the following specific examples. It should be understood that these examples are for illustrative purposes only and are not intended to limit the scope of the present invention. Furthermore, it should be understood that various changes or modifications can be made by those skilled in the art after reading the description of the present invention, and such equivalents also fall within the scope of the invention.

EXAMPLE 1 preparation of dressing

10 g of hyaluronic acid (weight average molecular weight 400kDa) was weighed and dissolved in 500 ml of deionized water to obtain a hyaluronic acid solution with a w/v concentration of 2.0%. 5.35 g of sodium periodate is weighed and added into the hyaluronic acid solution, and stirred at room temperature for 24 hours in the dark, and 5 ml of ethylene glycol is added and stirred for 1 hour to terminate the reaction. Dialyzing the obtained solution in deionized water for five days to obtain 860 mL of oxidized hyaluronic acid solution, and determining the concentration of the oxidized hyaluronic acid in the obtained solution to be 8.6mg/mL by solid content detection.

10 g of gelatin was weighed and dissolved in 100 ml of 0.1M (0.1mol/L) acetic acid solution to obtain a 10% w/v gelatin solution. 232 ml of the oxidized hyaluronic acid solution is taken and dripped into the gelatin solution, and the mixture is stirred until a uniform solution is obtained. The pH of the resulting solution was adjusted to about 7 with 1M (1.0mol/L) NaOH solution, freeze dried, vacuum dried at 105 deg.C to remove water to give a yellow sponge solid, and pulverized to give 11.6 g of powder.

EXAMPLE 2 preparation of dressing

4 g of starch (weight average molecular weight 60kDa) were weighed and dissolved in 100 ml of deionized water to give a starch solution with a w/v concentration of 4.0%. 5.35 g of sodium periodate is weighed and added into the starch solution, and stirred at room temperature for 12 hours in the dark, and 5 ml of ethylene glycol is added and stirred for 1 hour to terminate the reaction. The resulting solution was dialyzed against deionized water for five days to obtain 153 mL of oxidized starch solution, and the concentration of oxidized starch in the resulting solution was determined to be 22.9mg/mL by solid content measurement.

10 g of gelatin was weighed and dissolved in 100 ml of 0.1M acetic acid solution to obtain a 10% w/v gelatin solution. 87 ml of the oxidized starch solution was added dropwise to the gelatin solution and stirred until a homogeneous solution was obtained. The pH of the resulting solution was adjusted to about 6 with 1M NaOH solution, freeze dried, then dried under vacuum at 105 ℃ to remove water to give a yellow sponge solid, which was pulverized to give 10.8 g of powder.

EXAMPLE 3 preparation of dressing

11.9 g of chondroitin sulfate (weight average molecular weight 100kDa) was weighed and dissolved in 100 ml of deionized water to obtain a chondroitin sulfate solution with a w/v concentration of 11.9%. 5.35 g of sodium periodate is weighed and added into chondroitin sulfate solution, and stirred for 10 hours at room temperature in the dark, and 5 ml of ethylene glycol is added and stirred for 1 hour to terminate the reaction. The obtained solution was dialyzed in deionized water for five days to obtain 348 mL of chondroitin sulfate oxide solution, and the concentration of chondroitin sulfate oxide in the obtained solution was determined to be 28.7mg/mL by solid content detection.

10 g of gelatin was weighed and dissolved in 1000 ml of 0.1M acetic acid solution to obtain a gelatin solution with a w/v concentration of 1.0%. 70 ml of the chondroitin sulfate oxide solution is dropwise added into the gelatin solution, the mixture is stirred until a uniform solution is obtained, the pH value of the solution is adjusted to about 8 by using 1M NaOH solution, the solution is firstly frozen and dried under vacuum at 105 ℃ to remove water, yellow sponge-shaped solid is obtained, and 11.9 g of powder is obtained after the powder is crushed.

EXAMPLE 4 preparation of dressing

7 g of carboxymethyl cellulose with the weight-average molecular weight of 100kDa is weighed and dissolved in 100 ml of deionized water to obtain a carboxymethyl cellulose solution with the w/v concentration of 7.0 percent. 5.35 g of sodium periodate is weighed and added into the carboxymethyl cellulose solution, and stirred for 8 hours at room temperature in a dark place, and 5 ml of ethylene glycol is added and stirred for 1 hour to terminate the reaction. The resulting solution was dialyzed against deionized water for five days to give 182 mL of a carboxymethyl cellulose oxide solution, and the concentration of carboxymethyl cellulose in the resulting solution was determined to be 27.5mg/mL by solid content measurement.

10 g of gelatin was weighed and dissolved in 500 ml of 0.1M acetic acid solution to obtain a gelatin solution with a w/v concentration of 2.0%. 73 ml of the carboxymethyl cellulose oxide solution is dropwise added into the gelatin solution, the mixture is stirred until a uniform solution is obtained, the pH value of the solution is adjusted to about 7 by using 1M NaOH solution, the solution is frozen and dried at 105 ℃ in vacuum to remove water, yellow sponge-shaped solid is obtained, and 11.2 g of powder is obtained after the powder is crushed.

EXAMPLE 5 preparation of liquid dressing

0.20 g of each of the dressings prepared in examples 1 to 4 was weighed and filled in a 3 ml syringe, respectively. Another 4 syringes of 3 mL are respectively taken to extract 1.0mL of physiological saline, the syringes are connected with the syringes with the dressing through luer joints, and the push rods of the syringes are pushed to and fro at least thirty times to obtain the liquid dressings I-IV in a light yellow homogeneous state (which respectively correspond to the embodiments 1-4).

EXAMPLE 6 curative Effect on Whole-layer defects of animal skin

Five full-layer skin excision was performed on the backs of about 250-300g SD rats (males) aged 8 weeks, with a circular area of 1.5cm diameter excised, full-layer skin depth, and no invasion of subcutaneous fascia and muscle, and wound surfaces were treated with 4 experimental groups (corresponding to the four liquid dressings prepared in example 5, respectively given to the liquid dressings I-IV prepared in example 5, single administration) and a blank control group (saline group, given to the same amount of saline as the experimental group, single administration) according to a random distribution principle, and continuously observed for 15 days. Wound size changes were recorded daily and wound healing rates were calculated and the results are shown in figure 1 and table 1 below.

TABLE 1 ratio of residual wound to initial wound

	Day 0	Day 10	Day 15
				Blank control group	100％	35％	16％
Dressing set I	100％	23％	＜3％
				Dressing set II	100％	26％	＜3％
Dressing group III	100％	20％	＜3％
				Dressing set IV	100％	28％	＜3％

The healing conditions of the wound at different time points show that compared with a blank control group, the biocompatible polymer dressing treatment group provided by the invention has the advantages that the average period of wound healing is obviously shortened, and the inflammatory reaction of the wound during healing is obviously reduced, so that the dressing provided by the invention can obviously promote wound healing, and has significant difference compared with the blank control group.

Example 7 sustained Release experiments

0.20 g of each of the dressings prepared in examples 1 to 4 was weighed and filled in a 3 ml syringe, respectively. Another 4 3 mL syringes were separately used to draw 1.0mL of a mixed Platelet Rich Plasma (PRP) solution in physiological saline (PRP concentration: 1250X 10)⁹and/L) is connected with a syringe with dressing through a luer connector, and the push rod of the syringe is pushed to and fro at least thirty times to obtain the liquid dressing I-IV containing PRP in a homogeneous state. The biologically active sustained-release properties of the biocompatible polymer compositions obtained in examples 1 to 4 were verified by this experiment. The PRP used was obtained from blood extraction of SD rats of approximately 250-300g body weight, containing various growth factors, and this experiment tested the effect of platelet-derived growth factor (PDGF) release.

The PRP-compounded hydrogel dressings I-IV are respectively placed on a semipermeable membrane, and the whole system is placed in an excessive phosphate buffer solution with the pH value of 7.5 +/-0.2 to carry out PDGF release experiments.

Through experimental observation lasting for 7 days, compared with the simple RPR, the biocompatible polymer dressing composition prepared by the invention can play a role of slow release after the PRP is compounded, and maintain the bioactivity of the biocompatible polymer dressing composition. The PDGF release efficiency is shown in table 2.

TABLE 2 PDGF Release efficiency

EXAMPLE 8 biocompatibility experiments

The dressings prepared in examples 1 to 4 were weighed out in an amount of 0.20 g each, and filled in a 3 ml syringe, respectively. And respectively extracting 1.0mL of the mixed solution of the normal saline of the mixed adipose-derived stem cells by taking 4 syringes of 3 milliliters, connecting the syringes with the dressing through luer connectors, and pushing a push rod of each syringe to and fro for at least thirty times to obtain the liquid dressing I-IV loaded with the stem cells in a homogeneous state.

The biotoxicity of the dressings obtained in examples 1-4 was determined by the activity and proliferation status of the loaded stem cells. The adipose-derived stem cells are obtained by purchasing, and the cell culture solution is prepared by DMEM composite double antibody (cyan/streptomycin) and fetal calf serum. The concentration of loaded cells was 1X10⁶Per ml dressing.

The stem cell loaded dressing was cultured routinely (37 degrees, 5% CO)₂Environment), and dead and live cell staining and cell counting were performed on days 1, 3, and 5, respectively.

The result shows that after the dressing is re-dissolved with the mixed solution of the physiological saline containing the stem cells to obtain the liquid dressing, more than 82 percent of cells in the four groups of dressings survive on the 1 st day of culture; cells continued to proliferate in all four dressings after 3 and 5 days of culture. This indicates that the dressing of the invention is biocompatible and contributes to cell survival and proliferation.

Claims (7)

1. A biocompatible polymer dressing based on gelatin is characterized by being prepared by a method comprising the following steps:

(1) dissolving polysaccharide in water to obtain polysaccharide solution, adding sodium periodate to oxidize polysaccharide, adding alcohol to terminate polysaccharide oxidation reaction, and dialyzing to obtain oxidized polysaccharide solution;

(2) dissolving gelatin in acid-containing water to obtain gelatin solution, adding oxidized polysaccharide solution dropwise into the gelatin solution, stirring for reaction until uniform solution is obtained, adjusting pH of the obtained solution to 6-8 if necessary, and drying to remove water to obtain solid dressing.

2. The dressing of claim 1, wherein the method further comprises the steps of:

(3) and crushing the obtained solid dressing to obtain the powder dressing.

3. The dressing of claim 2, wherein said method further comprises the steps of:

(4) and re-dissolving the obtained powder dressing with a biocompatible sterile solution to obtain the liquid dressing.

4. The dressing of claim 1 wherein the polysaccharide is hyaluronic acid, chondroitin sulfate, starch and/or carboxymethylcellulose.

Preferably, the hyaluronic acid has a weight average molecular weight of 3kDa-2MDa, preferably 400kDa-1 MDa;

the weight average molecular weight of the chondroitin sulfate is 10kDa-300 kDa;

the weight average molecular weight of the starch is 10kDa-100 kDa;

the weight average molecular weight of the carboxymethyl cellulose is 10kDa to 1MDa, preferably 10kDa to 400 kDa.

Preferably, in step (1), the concentration (weight/volume) of the polysaccharide solution is 0.1% to 15.0%.

Preferably, in step (1), the ratio of the molar amount of sodium periodate to the molar amount of units of polysaccharide is from 4: 1 to 1: 10.

Preferably, in step (1), the oxidation reaction is carried out for 2 to 48 hours at room temperature with the exclusion of light.

Preferably, in step (1), the alcohol is ethylene glycol, glycerol, mercaptoethanol, and/or ethylene glycol, etc. Preferably, the alcohol is used in an amount of 1.0-4.0mL per 1.07 g of sodium periodate used.

5. The dressing of claim 1 wherein in step (2) the acid is acetic acid, hydrochloric acid, propionic acid, formic acid, sulfuric acid, phosphoric acid, or the like. Preferably, the concentration of the acid is from 0.01mol/L to 1.0 mol/L.

Preferably, in step (2), the concentration (weight/volume) of the gelatin solution is 0.1% to 20%.

Preferably, in step (2), the weight ratio of oxidized polysaccharide to gelatin is 1: 99 to 95: 5, preferably 5: 95 to 50: 50, more preferably 8: 92 to 20: 80.

Preferably, in step (2), the freeze-drying is performed first, and then the vacuum drying is performed at 100-110 ℃ to remove the water.

6. The dressing of claim 1, wherein in step (4), the biocompatible sterile solution is saline for injection or glucose solution for injection.

Preferably, in step (4), the biocompatible sterile solution further contains an active substance for promoting wound healing, such as Platelet Rich Plasma (PRP), various growth factors, drugs, stem cells, and the like.

7. Use of the dressing of any one of claims 1-6 in the biomedical and cosmetology field. In particular to application in preparing a dressing for treating wounds.

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