CN113061265A

CN113061265A - Polysaccharide hydrogel, preparation method and application thereof

Info

Publication number: CN113061265A
Application number: CN202110189854.9A
Authority: CN
Inventors: 石小鹏; 张伟; 马善波; 张蕊; 缪珊; 宋保强; 乔逸; 李龙; 王锦
Original assignee: Air Force Medical University of PLA
Current assignee: Air Force Medical University of PLA
Priority date: 2021-02-18
Filing date: 2021-02-18
Publication date: 2021-07-02

Abstract

The invention belongs to the technical field of biological medicines, and particularly relates to polysaccharide hydrogel, and a preparation method and application thereof. The polysaccharide hydrogel is formed by crosslinking a mixed solution containing carboxymethyl chitosan and bletilla striata polysaccharide by 1, 4-butanediol glycidyl ether. The polysaccharide hydrogel disclosed by the invention has good mechanical properties and antibacterial properties, and is free from cytotoxicity; the preparation method is simple to operate, mild in reaction conditions and wide in material source, and can be used as a dressing for promoting skin wound healing.

Description

Polysaccharide hydrogel, preparation method and application thereof

Technical Field

The invention belongs to the technical field of biological medicines, and particularly relates to polysaccharide hydrogel, and a preparation method and application thereof.

Background

The skin is used as the first immunological defense line of human body, and has the functions of protecting human body tissue and organ from external mechanical and chemical stimulation and virus and bacteria invasion. Wound healing is a physiological process involved in the repair of injury, restoration of anatomical integrity and function of the injured site of living tissue after skin injury. The skin wound repair process is divided into four stages: hemostasis phase, inflammatory response phase, granulation tissue proliferation phase, re-epithelialization and tissue remodeling phase. The dressing is used as a wound surface covering material, and can play a role in temporarily protecting a wound, preventing infection to a certain extent, providing a beneficial microenvironment for wound surface healing and promoting wound healing.

Although conventional dressings such as gauze and cotton pad have good water absorption, are simple to manufacture, are cheap and widely used, granulation tissues formed on the surface of a wound are easy to adhere to the dressings in the healing process, so that secondary wound is generated on the wound when dressing change is performed. The most ideal wound dressing at present is transplanted skin, but the development of the wound dressing is restricted by limited skin source, high preservation condition, susceptibility to pathogenic microorganisms and high price. The film dressing made of the transparent polyurethane film has good air permeability, cannot permeate liquid and microorganisms, but has poor water absorption, and is only suitable for dry superficial wounds but not suitable for wounds with more exudates.

In recent years, hydrogel dressings have attracted wide attention, and the hydrogel dressings have the advantages of high water content, capability of keeping wound surfaces in a moist environment, convenience for granulation growth, good moisture retention, toughness and strength, capability of being tightly pasted on the surfaces of irregular wound wounds, reduction in bacterial invasion, capability of absorbing a large amount of exudates, shortening of dressing change times and alleviation of pain of patients.

Hydrogel dressings have been reported to incorporate cross-linking agents of small molecular aldehydes, such as formaldehyde, glutaraldehyde, etc., during the preparation process. Aldehyde cross-linking agents can produce severe cytotoxicity, which can seriously affect wound healing. Therefore, it is important to develop a safer hydrogel dressing.

In view of this, the invention is particularly proposed.

Disclosure of Invention

The primary object of the present invention is to provide a polysaccharide hydrogel.

The second object of the present invention is to provide a method for producing the polysaccharide hydrogel.

The first and third objects of the present invention are to provide applications of the polysaccharide-based hydrogel.

In order to achieve the purpose of the invention, the technical scheme is as follows:

the invention provides a polysaccharide hydrogel which is formed by crosslinking a mixed solution containing carboxymethyl chitosan and bletilla striata polysaccharide by 1, 4-butanediol glycidyl ether.

Optionally, in the mixed solution, the mass percentage concentration of the carboxymethyl chitosan is 1.5-4.5%, preferably 2-4%, and most preferably 3%.

Optionally, in the mixed solution, the mass percentage concentration of the bletilla striata polysaccharide is 1-3%, preferably 1.5-2.5%, and most preferably 2%.

Optionally, the mass ratio of the carboxymethyl chitosan to the bletilla striata polysaccharide is 2-4: 2, preferably 3: 2.

optionally, in the mixed solution, the mass percentage concentration of the 1, 4-butanediol glycidyl ether is 0.1-0.5%, and preferably 0.25%.

Optionally, the molecular weight of the bletilla striata polysaccharide is 400-500, and the molecular weight of the carboxymethyl chitosan is 10-20 ten thousand.

Optionally, the polysaccharide hydrogel has fluidity at 20-30 ℃, and preferably, the viscosity of the polysaccharide hydrogel at 20-30 ℃ is 10 mpa.s-80 mpa.s.

The invention also relates to a preparation method of the polysaccharide hydrogel, which comprises the following steps:

s1, preparing a carboxymethyl chitosan aqueous solution and a bletilla striata polysaccharide aqueous solution respectively;

s2, mixing the carboxymethyl chitosan aqueous solution and the bletilla striata polysaccharide aqueous solution according to the weight ratio of 1:1 to obtain a mixed solution;

s3, adding 1, 4-butanediol glycidyl ether, and heating at 45-53 ℃ for 15-30 min to obtain the polysaccharide hydrogel, preferably heating at 50 ℃ for 20 min.

The invention also relates to the use of polysaccharide hydrogels for the production of dressings for skin wounds.

Optionally, the dressing is a dressing that promotes skin wound repair.

The invention has at least the following beneficial effects:

the polysaccharide hydrogel disclosed by the invention has good mechanical properties and antibacterial properties, and is free from cytotoxicity. The preparation method of the polysaccharide hydrogel is simple to operate, mild in reaction conditions and wide in material source, so that the polysaccharide hydrogel can be used as a dressing for promoting skin wound healing.

Drawings

FIG. 1 is the microstructure of a gel under an electron microscope;

FIG. 2 is a morphogram of a gel used in a mouse skin lesion model;

FIG. 3 is a photograph of skin wound healing;

FIG. 4 is a statistical line graph of skin wound diameter;

FIG. 5 is a graph of the staining of a pathological section HE of a skin wound;

FIG. 6 is a Masson staining chart of a skin wound histopathological section;

FIG. 7 is a view showing the self-healing of the hydrogel of example 1;

FIG. 8 shows the results of MTT experiments with gel cross-linking agents;

FIG. 9 shows the results of comparative experiments on the shear thinning behavior of gels at 37 ℃;

FIG. 10 is a graph of water absorption as a function of time;

FIG. 11 is a graph of water absorption as a function of time;

FIG. 12 is a graph of water loss versus time;

FIG. 13 is a graph of water loss rate as a function of time;

FIG. 14 comparative test procedure of self-healing capacity of gel;

figure 15 gel self-healing ability comparative test results.

Detailed Description

The present invention is further illustrated by the following examples and comparative examples, which are intended to be illustrative only and are not to be construed as limiting the invention. It is intended to cover by the present invention all such modifications as come within the scope of the invention as defined by the appended claims.

The embodiment of the invention relates to polysaccharide hydrogel which is formed by crosslinking a mixed solution containing carboxymethyl chitosan and bletilla striata polysaccharide by 1, 4-butanediol glycidyl ether.

Bletilla striata is a traditional Chinese herbal medicine, and the tuber of the bletilla striata is rich in polysaccharide (accounting for about 55-60 percent of the original medicinal plants) and is the main medicinal active ingredient. The bletilla striata polysaccharide has the effects of inhibiting generation of tumor blood vessels, resisting infection and oxidation, promoting blood coagulation, reducing swelling, healing sore, removing nodule and promoting granulation, and is an excellent natural biological adhesive. The preparation method of the bletilla striata polysaccharide comprises the following steps: (1) crushing: pulverizing rhizoma bletilla tuber to obtain rhizoma bletilla coarse powder; (2) ultrasonic treatment: adding a proper amount of water into the bletilla striata coarse powder prepared in the step (1), and performing ultrasonic extraction to obtain an ultrasonic treatment liquid; (3) and (3) enzymolysis treatment: adding cellulase into the ultrasonic treatment liquid prepared in the step (2) for treatment, and centrifuging after treatment to obtain a bletilla striata polysaccharide extracting solution; (4) and (4) microfiltration concentration: and (4) performing tangential flow filtration on the bletilla striata polysaccharide extracting solution prepared in the step (3) by using a ceramic membrane filter, and collecting microfiltration trapped fluid with required concentration to obtain colloidal liquid bletilla striata polysaccharide. Chitosan is the second largest biological macromolecule next to cellulose in nature, wherein chitosan gel dressing has biocompatibility, hemostatic property, antibacterial property and capability of promoting wound healing. The embodiment of the invention adopts the safe cross-linking agent, namely 1, 4-butanediol glycidyl ether to replace the prior aldehyde cross-linking agent, so that the biocompatibility and the safety of the polysaccharide hydrogel are greatly improved. The polysaccharide hydrogel provided by the embodiment of the invention has good mechanical properties; the self-healing gel dressing has a self-healing function, and can heal automatically when the gel dressing is broken due to external force; has no cytotoxicity, and the selected cross-linking agent is safer than aldehyde cross-linking agent.

Specifically, in the mixed solution of the embodiment of the invention, the mass percentage concentration of the carboxymethyl chitosan is 1.5-4.5%. If the concentration of the carboxymethyl chitosan is too high, the fluidity is poor, and the treatment cannot be carried out; if the concentration is too low, the fluidity is too high, which results in poor gel-forming state, so 2-4% is selected, and 3% is most preferred.

Specifically, in the mixed solution of the embodiment of the present invention, the concentration of the bletilla striata polysaccharide in percentage by mass is 1 to 3%, preferably 1.5 to 2.5%, and most preferably 2%.

Specifically, in the mixed solution of the embodiment of the invention, the mass ratio of the carboxymethyl chitosan to the bletilla striata polysaccharide is 2-4: 2, preferably 3: 2.

specifically, in the mixed solution of the embodiment of the present invention, the mass percentage concentration of 1, 4-butanediol glycidyl ether in the mixed solution of the embodiment of the present invention is 0.1 to 0.5%, and preferably 0.25%. If the addition amount of 1, 4-butanediol glycidyl ether is too large, the gel hardness is too large and self-healing is not possible. If the amount of 1, 4-butanediol glycidyl ether added is too small, the degree of crosslinking of the gel becomes insufficient, and the gel cannot be formed.

Specifically, the molecular weight of the bletilla striata polysaccharide in the embodiment of the invention is 400-500, and the molecular weight of the carboxymethyl chitosan is 10-20 ten thousand.

Specifically, the polysaccharide hydrogel of the present invention has fluidity at 20 to 30 ℃, and preferably, the polysaccharide hydrogel has a viscosity of 10mpa.s to 80mpa.s (cps) at 20 to 30 ℃.

The embodiment of the invention also relates to a preparation method of the polysaccharide hydrogel, which comprises the following steps:

s2, fully and uniformly mixing the carboxymethyl chitosan aqueous solution and the bletilla striata polysaccharide aqueous solution according to the volume of 1:1 to obtain a mixed solution;

s3, adding 1, 4-butanediol glycidyl ether, and heating at 45-53 ℃ for 15-30 min to obtain the medical polysaccharide hydrogel.

Wherein, in the carboxymethyl chitosan water solution, the mass percentage concentration of the carboxymethyl chitosan is 3-9%, preferably 4-8%, and most preferably 6%.

Specifically, in the bletilla striata polysaccharide aqueous solution, the mass percentage concentration of the bletilla striata polysaccharide is 2-6%, preferably 3-5%, and most preferably 4%.

Preferably, the heating condition is 50 ℃ for 20 min.

The polysaccharide hydrogel provided by the embodiment of the invention adopts a chemical crosslinking method, takes effect with amino on chitosan by utilizing epoxy bonds, is simple to operate, mild in reaction conditions and low in cost, does not use any organic solvent, and can effectively avoid the problems of cytotoxicity and the like caused by introduction of aldehyde crosslinking agents and other solvents.

The embodiment of the invention also relates to application of the polysaccharide hydrogel in preparing a dressing for skin wounds. In particular, the dressing of the embodiments of the present invention is a dressing for promoting skin wound repair.

The polysaccharide hydrogel provided by the embodiment of the invention can be applied to the field of preparation of dressings for promoting wound healing, and gel dressings in any shapes can be prepared according to the requirements of different skin wounds, so that the purpose of promoting wound healing is achieved.

Example 1

1. Dissolving carboxymethyl chitosan in deionized water to prepare 6 wt% of carboxymethyl chitosan aqueous solution, and dissolving bletilla polysaccharide in deionized water to prepare 4 wt% of bletilla polysaccharide aqueous solution;

2. the two solutions were mixed as described in 1:1, and placing the mixture in a 5mL EP tube, wherein the blank carboxymethyl chitosan aqueous solution and the mixed solution have fluidity at room temperature.

3. Standing the mixed solution, and adding 1, 4-butanediol glycidyl ether in proportion to enable the mass percentage concentration of the 1, 4-butanediol glycidyl ether in the mixed solution to be 0.25%; the mixture was heated at 50 ℃ for 20min, and the fluidity of the mixture was observed by inverting the EP tube, whereby the fluidity was slow, and a polysaccharide hydrogel was formed.

Self-healing function experiment: preparing the hydrogel into a columnar shape, splicing the two cut pieces together after 1min, and observing the self-healing phenomenon after 5 min. The results are shown in fig. 7, which shows that the gel dressing can heal by itself when it is broken by an external force. Preparing a hydrogel graph a according to the technical scheme, and preparing a colored hydrogel graph b; and then cutting a and b respectively, and removing one section of the alignment graph c respectively to obtain the self-healing result shown as a graph d.

Examples 2 to 5 and comparative examples 1 to 4

Polysaccharide hydrogels were prepared as in example 1, with the differences shown in table 2.

The physical properties of the polysaccharide hydrogel thus obtained are shown in Table 3.

TABLE 3

	Physical Properties
		Example 2	Is in the form of colloid and has slight fluidity
Example 3	Is in gel form, has no fluidity, and has dark color
		Example 4	It was in the form of gel, had no fluidity, and was darker in color than example 3
Example 5	Is in the form of a gel, has slight fluidity, and has fluidity lower than that of example 2
		Comparative example 1	Is in gel form, has no fluidity, and has light color
Comparative example 2	Is in the form of colloid and has slight fluidity
		Comparative example 3	Is in gel form, hard and dark
Comparative example 4	Is colloidal and has a slight fluidity which is inferior to that of comparative example 2

Experimental example 1 polysaccharide hydrogel morphology characterization experiment

The polysaccharide hydrogel sample obtained in example 1 was freeze-dried in a vacuum freeze-dryer, and the dried polysaccharide hydrogel sample was taken out and cut in liquid nitrogen. And fixing the gel section with conductive adhesive, spraying gold, and observing the microscopic morphology of the sample section by a scanning electron microscope, as shown in fig. 1.

From fig. 1, it can be observed that the polysaccharide hydrogel has a dense three-dimensional network pore structure, illustrating that the structure facilitates the transport and diffusion of oxygen molecules, water molecules, metabolites, and drugs. This allows the polysaccharide hydrogel material to have good permeability and permeability as a wound healing promoting dressing. The mechanism for forming the polysaccharide hydrogel structure is probably that amino contained in the molecular structure of carboxymethyl chitosan reacts with epoxy bonds of 1, 4-butanediol glycidyl ether, and long chains of chitosan are intertwined to form a three-dimensional network structure. The good space network structure of the gel wraps bletilla striata polysaccharide, and potential possibility is provided for skin wound repair.

Experimental example 2 polysaccharide hydrogel test for promoting healing of skin wound.

Selecting Kunming mouse as experimental animal, depilating back, and cutting a circular incision with diameter of 0.7cm with surgical scissors to obtain mouse skin injury model. The polysaccharide hydrogel prepared in example 1 was shaped in a mold and applied to a circular wound on the back as shown in fig. 2. It was observed that the polysaccharide hydrogel was stably attached to the skin wound.

The polysaccharide hydrogel group of the present invention was designated as a CMCS gel-treated group, and a commercial 3M film dressing was used as a control. The recovery of wound on the back of the mice was observed daily, and the wound diameter was measured at 3, 7 and 14 days and recorded by photographing, as shown in fig. 3, and the statistical wound diameter data is shown in fig. 4. Daily wound healing contrast was clearly observed, with the CMCS gel treated group having substantially healed wounds at day ten, while the placebo and 3M membrane treated groups had not healed. The chitosan/bletilla striata polysaccharide hydrogel can be proved to have the effect of promoting wound healing.

The wound tissues of untreated skin, 3M membrane treated skin and CMCS gel treated mice were subjected to pathological section HE staining on

days

3, 7 and 14, respectively, and observed under a microscope to obtain fig. 5. As can be seen in fig. 5, after 3 days of wound repair, epidermal layer repair had occurred in the CMCS gel-treated group, whereas no epidermal layer was formed in the control group and the 3M group. After 7 days of wound repair, the control and 3M groups began to form a skin, but was thin and had inflammatory cell infiltration, whereas the CMCS gel treated group had developed a large number of hair follicles. The CMCS gel treated group of neonatal skin tissue was roughly consistent with normal skin after 14 days. The CMCS gel is shown to have good effects of promoting skin wound repair relative to 3M membrane and blank control treatment.

Wound tissue from untreated skin, 3M membrane treated skin and CMCS gel treated mice were Masson stained for pathological sections on

days

3, 7 and 14, respectively, and observed under a microscope as fig. 6. As can be seen from fig. 6, collagen in the dermis of the CMCS gel-treated group began to proliferate after 3 days. After 7 days, the CMCS gel treated group had significantly thickened epidermis and increased hair follicles, whereas the control and 3M groups had few hair follicles and had inflammatory cell infiltration. The CMCS gel is shown to have good effects of promoting skin wound repair relative to 3M membrane and blank control treatment.

Experimental example 3 MTT experiment of gel crosslinking agent

Glutaraldehyde and beta-sodium glycerophosphate were used to prepare the comparative drug:

comparative drug 1: a gel was prepared as in example 1, except that glutaraldehyde was used instead of 1, 4-butanediol glycidyl ether.

Comparative drug 2: a gel was prepared as in example 1, except that sodium beta-glycerophosphate was used in place of 1, 4-butanediol glycidyl ether.

The MTT experiment was performed using comparative drug 1, comparative drug 2 and the formulation of example 1, using the following specific test methods: taking HaCaT cells in logarithmic phase, washing for 2 times by PBS, collecting after trypsinization, centrifuging for 5min at 1000rpm, removing supernatant, and adding a proper amount of culture medium to obtain single cell suspension; counting with a blood counting chamber, adjusting cell density to 5 × 10⁴Perml, 100. mu.L/well in 96-well plates, set up in different groups, 3 replicates per group, 37 ℃, 5% CO₂Culturing at constant temperature, and adding corresponding medicine after the cells adhere to the wall.

After the drug acts for 24 hours, the supernatant is sucked and removed, and 200 mu L of MTT solution with the final concentration of 0.5mg/mL is added into each hole; and gently shaking the plate several times at 37 deg.C with 5% CO₂Continuously culturing for 4h at constant temperature; the solution was aspirated off, 150. mu.L of DMSO was added to each well, the mixture was shaken in the dark for 10min, and the absorbance at 570nm was measured using a microplate reader.

The test results are shown in FIG. 8. As can be seen from FIG. 8, glutaraldehyde toxicity was the greatest and 1, 4-butanediol glycidyl ether gel was the least cytotoxic.

Experimental example 4 shear thinning behavior of gel at 37 deg.C

Polysaccharide hydrogels were prepared according to the method of example 1, wherein the polysaccharide hydrogels were 0.25% of the cross-linking agent (3% by mass of carboxymethyl chitosan, 2% by mass of bletilla polysaccharide, and 0.25% by mass of 1, 4-butanediol glycidyl ether) and 0.5% of the cross-linking agent (3% by mass of carboxymethyl chitosan, 2% by mass of bletilla polysaccharide, and 0.5% by mass of 1, 4-butanediol glycidyl ether). The polysaccharide hydrogel is used for preparing a hydrogel wafer (n is 3) with the diameter of 2cm and the thickness of 1mm, an Antopa rheometer (MCR302) is used for carrying out a shear viscosity test on a sample, and the shear rate is 0.1-117S^-1The temperature was 37 ℃. The test results are shown in FIG. 9.

As can be seen from FIG. 9, the shear rate is 0.1 to 10S^-1The gel exhibited stable shear-thinning behavior and the viscosity was reduced by approximately one order of magnitude. Compared with 0.5% gel, 0.25% cross-linking agent gel has the advantages that the viscosity is reduced continuously along with the rapid increase of the shear rate, more excellent shear thinning behavior is shown, and the better injectability is proved.

Experimental example 5 Water-holding Capacity test

The polysaccharide hydrogel prepared in example 1 had a water loss ratio and a water absorption ratio:

water absorption: accurately weighing a certain mass of gel to obtain an initial mass (W)₀) And placed in a 250 ml beaker. Adding a certain amount of water into the beaker until the gel is completely immersed, standing at room temperature for 20h, taking out the gel every 2h, placing the gel in a culture dish, sucking off the water on the surface of the gel, and accurately weighing the mass (W)_t) The water absorption was calculated using the following formula:

water absorption (%) - (W)_t-W₀)/W₀×100％

Water loss rate: a certain mass of the gel was taken, placed in a 5ml EP tube, and the initial mass (W) was accurately weighed₀). Placing the EP tube into a silica gel dryer, standing at room temperature for 24h, taking out every 2h, and accurately weighing mass (W)_t) The water loss rate is expressed by the following formulaAnd (3) calculating:

water loss (%) - (W)₀-W_t)/W₀×100％

The water absorption capacity with time is shown in FIG. 10, and the water absorption capacity with time is shown in FIG. 11; water absorption: 1560.72% (n-3). A graph of the change of the water loss amount with time is obtained and is shown in fig. 12, and a graph of the change of the water loss rate with time is shown in fig. 13; the water loss rate was 3.87% (n ═ 3). The experiment shows that the gel has high water absorption and little water loss, and further proves that the gel has better water retention capacity.

Experimental example 6 comparative test of self-healing Capacity of gel

0.25% of hydrogel (the concentration of carboxymethyl chitosan is 3% by mass, the concentration of bletilla polysaccharide is 2% by mass, the concentration of 1, 4-butanediol glycidyl ether is 0.25% by mass), 0.5% of hydrogel (the concentration of carboxymethyl chitosan is 3% by mass, the concentration of bletilla polysaccharide is 2% by mass, the concentration of 1, 4-butanediol glycidyl ether is 0.5% by mass), 1% (the concentration of carboxymethyl chitosan is 3% by mass, the concentration of bletilla polysaccharide is 2% by mass, the concentration of 1, 4-butanediol glycidyl ether is 1% by mass) are prepared according to the method of example 1; the polysaccharide hydrogel is prepared into hydrogel wafer with diameter of 2cm and thickness of 1mm, and is cut by a knife, the two cut pieces are spliced together after 1min, and the self-healing phenomenon is observed after 5 min. So that the other end is not separated after lifting one end and has self-healing capability. The results are shown in FIGS. 14 and 15.

As can be seen from fig. 14 and 15, the self-healing ability of the 0.25% polysaccharide hydrogel was the best, and the hardness of the 0.5% hydrogel and the 1% hydrogel were too high to be self-healing.

Although the present application has been described with reference to preferred embodiments, it is not intended to limit the scope of the claims, and many possible variations and modifications may be made by one skilled in the art without departing from the spirit of the application.

Claims

1. The polysaccharide hydrogel is characterized in that the polysaccharide hydrogel is formed by crosslinking a mixed solution containing carboxymethyl chitosan and bletilla striata polysaccharide by 1, 4-butanediol glycidyl ether.

2. The polysaccharide hydrogel according to claim 1, wherein the concentration of carboxymethyl chitosan in the mixed solution is 1.5 to 4.5% by mass, preferably 2 to 4% by mass, and most preferably 3% by mass.

3. The polysaccharide hydrogel according to claim 1, wherein the concentration of bletilla striata polysaccharide in the mixed solution is 1-3% by mass, preferably 1.5-2.5% by mass, and most preferably 2% by mass.

4. The polysaccharide hydrogel according to claim 1, wherein the mass ratio of carboxymethyl chitosan to bletilla striata polysaccharide is 2-4: 2, preferably 3: 2.

5. the polysaccharide hydrogel according to claim 1, wherein the concentration of 1, 4-butanediol glycidyl ether in the mixed solution is 0.1 to 0.5% by mass, preferably 0.25% by mass.

6. The polysaccharide hydrogel according to claim 1, wherein the bletilla polysaccharide has a molecular weight of 400 to 500, and the carboxymethyl chitosan has a molecular weight of 10 to 20 ten thousand.

7. The polysaccharide hydrogel according to any one of claims 1 to 6, wherein the polysaccharide hydrogel has fluidity at 20 to 30 ℃, and preferably has a viscosity of 10mPa.s to 80mPa.s at 20 to 30 ℃.

8. The method for producing a polysaccharide hydrogel according to any one of claims 1 to 7, comprising the steps of:

9. Use of the polysaccharide hydrogel according to any one of claims 1 to 7 for the preparation of a dressing for a skin wound.

10. The use of claim 9, wherein the dressing is a dressing for promoting skin wound repair.