Wound repair gel responding to wound microenvironment and preparation method thereof

Abstract

The invention relates to the technical field of gels, and particularly discloses a wound repair gel responding to a wound surface microenvironment and a preparation method thereof, the gel is prepared from the following raw materials in percentage by mass: 3.0%-6.0% of a response gel matrix, 0.5%-2.0% of an active pharmaceutical ingredient, 0.5%-1.2% of a bionic repair component, 2.0%-4.0% of a moisturizing and stabilizing agent and the balance of water for injection. The response gel matrix comprises oxidized sodium alginate and methylacryloylated chitosan, the active drug component comprises a pH sensitive antibacterial drug and an enzyme sensitive healing promoting drug, and the bionic repairing component is a compound of recombinant human collagen and zinc sulfate. Bacterial reproduction is timely inhibited and infection is controlled at the early stage of wound healing; after entering the later healing stage, the composition continuously promotes epithelial cell proliferation and tissue regeneration, and meanwhile, the composition can remarkably promote tissue regeneration, reduce scar formation and realize antibacterial and healing-promoting synergy.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of gels, and particularly relates to a wound repair gel responding to a wound microenvironment and a preparation method thereof. BACKGROUND

[0002] Wound repair is an important research direction in the fields of clinical surgery, burn department, etc., and its core goal is to quickly control wound infection and promote tissue regeneration, and ultimately achieve functional healing of the wound. As the largest barrier organ of the human body, the skin, once damaged (such as burns, mechanical damage, chronic ulcers, etc.), will not only destroy the barrier function of the body, but also easily cause bacterial infection, excessive inflammatory response, etc., and in severe cases, will lead to delayed healing, scar proliferation, and even tissue necrosis, causing physiological pain and economic burden to the patient. Therefore, developing a wound repair material with efficient antibacterial, precise healing promotion, and good biocompatibility is of great significance to improve the clinical wound treatment effect

[0003] At present, the commonly used wound repair materials in clinical practice mainly include traditional dressings (such as gauze, vaseline gauze) and new biological materials (such as hydrogel gels, electrospun membranes, tissue engineering scaffolds, etc.). Among them, gel materials have become a research hotspot in the field of wound repair due to their good hydrophilicity, biocompatibility, ability to closely adhere to the wound, and ability to maintain a moist healing environment.

[0004] Wound healing is a dynamic multi-stage process, and the physiological needs at different stages are significantly different. However, the existing drug-loaded gels are mostly passive diffusion type drug release, and the drug release rate cannot match the dynamic needs of wound healing, often resulting in insufficient antibacterial drug concentration in the early stage leading to increased infection, or excessive consumption of healing-promoting drugs in the later stage affecting the repair effect. At the same time, the existing gel materials lack such biomimetic components, or only add a single component, and cannot construct a biomimetic repair microenvironment through the synergistic effect of components, resulting in poor tissue regeneration and easy formation of scars after healing. SUMMARY

[0005] The present application aims to provide a wound repair gel responding to a wound microenvironment and a preparation method thereof to solve the problems raised in the background.

[0006] To achieve the above-mentioned purpose, the present application provides the following technical solutions:

[0007] A wound repair gel responding to a wound microenvironment, the gel is prepared from the following mass percentage components:

[0008] 3.0%-6.0% of a responsive gel matrix, 0.5%-2.0% of an active pharmaceutical ingredient, 0.5%-1.2% of a biomimetic repair component, 2.0%-4.0% of a moisturizing and stabilizing agent, and the balance of water for injection.

[0009] The responsive gel matrix comprises oxidized sodium alginate and methacrylated chitosan, the active pharmaceutical ingredient comprises pH-sensitive antibacterial drug and enzyme-sensitive healing-promoting drug, and the biomimetic repair component is a complex of recombinant human collagen and zinc sulfate.

[0010] Preferably, the oxidation degree of the oxidized sodium alginate in the responsive gel matrix is 15%-35%, and the mass percentage is 1.5%-3.0%; the degree of substitution of the methacrylated chitosan is 40%-70%, and the mass percentage is 1.5%-3.0%.

[0011] Preferably, in the active pharmaceutical ingredient: the pH-sensitive antibacterial drug is minocycline hydrochloride connected to the molecular chain of oxidized sodium alginate through a hydrazone bond, wherein the drug loading amount of minocycline hydrochloride is 10%-20% of the mass of oxidized sodium alginate.

[0012] Preferably, the enzyme-sensitive healing-promoting drug is recombinant human epidermal growth factor connected to methacrylated chitosan through a matrix metalloproteinase MMP-cleavable peptide segment, and the mass percentage is included in the methacrylated chitosan, wherein the drug loading amount of recombinant human epidermal growth factor is 0.5%-2.0 of the mass of methacrylated chitosan.

[0013] Preferably, the recombinant human collagen is type III collagen, and the mass percentage is 0.3%-0.8%; the mass percentage of zinc sulfate is 0.2%-0.4%, and the zinc sulfate forms a complex with the recombinant human collagen through ionic interaction.

[0014] Preferably, the moisturizing and stabilizing agent is a mixture of glycerol and sodium hyaluronate, and the mass ratio of glycerol to sodium hyaluronate is 3:1-5:1.

[0015] A preparation method of a segmented drug release type repair gel, comprising the following steps:

[0016] S1, preparation of a drug-loaded responsive matrix:

[0017] Preparation of a pH-responsive drug-loaded component: disperse the oxidized sodium alginate in a buffer solution with a pH of 4.5-5.5, add minocycline hydrochloride under stirring, then add the catalyst p-toluenesulfonic acid, and react at 40-50°C for 12-24 hours. After the reaction is completed, dialysis and lyophilization are performed to obtain oxidized sodium alginate connected with minocycline hydrochloride through a hydrazone bond; dissolve the product in part of water for injection to obtain solution A;

[0018] Preparation of enzyme-responsive drug-loaded component: methacrylated chitosan is dissolved in a pH 6.0-7.0 buffer solution containing 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide and N-hydroxysuccinimide to activate the carboxyl group; an MMP-cleavable peptide segment with an amino group at one end is added for coupling reaction; after the reaction product is purified, secondary coupling is carried out with the amino terminal of recombinant human epidermal growth factor under mild conditions, and finally methacrylated chitosan with growth factor connected through a peptide segment is obtained; the product is dissolved in another part of water for injection to obtain solution B;

[0019] S2, preparation of gel premix: under light shielding conditions, solution A is mixed with solution B, a complex of recombinant human collagen and zinc sulfate, and a mixture of glycerol and sodium hyaluronate, and stirred uniformly at 4-25 DEG C to form a uniform and flowable gel premix;

[0020] S3, photo-crosslinking solidification and molding: the gel premix prepared in step S2 is placed in a mold or directly coated on a target surface, and irradiated with a visible light source with a wavelength of 365-405 nm for 20-40 seconds to make it crosslink and solidify into an elastic three-dimensional network gel.

[0021] Preferably, the molar ratio of the oxidized sodium alginate to minocycline hydrochloride is 1:0.8-1.2; and the buffer solution is sodium acetate buffer or sodium citrate buffer.

[0022] Preferably, the complex of recombinant human collagen and zinc sulfate is prepared by dissolving recombinant human type III collagen in water for injection, slowly adding a zinc sulfate solution under stirring, and complexing at 4 DEG C for 2-4 hours, and then freeze-drying; wherein the mass ratio of recombinant human collagen to zinc sulfate is 1.5:1-2.

[0023] Compared with the prior art, the present application has the following beneficial effects:

[0024] The present application couples different active drugs with a responsive gel matrix, which ensures that in the early stage of wound healing, the acidic microenvironment of the wound can trigger the cleavage of the hydrazone bond, so that the minocycline hydrochloride loaded on the oxidized sodium alginate is rapidly released to timely inhibit bacterial reproduction and control infection; in the later stage of healing, the locally elevated matrix metalloproteinase (MMP) in the wound can specifically cleave the peptide segment, so that the recombinant human epidermal growth factor on the methacrylated chitosan is slowly released to continuously promote epithelial cell proliferation and tissue regeneration, and the segmented drug release mode guarantees the physiological needs in different healing stages of the wound.

[0025] Meanwhile, the application adds a complex of recombinant human type III collagen and zinc sulfate, wherein the type III collagen is the main component of the extracellular matrix in the early stage of wound healing of the human body, can provide a natural biomimetic scaffold for cell proliferation and migration; the zinc sulfate can not only regulate the activity of MMP, promote the synthesis of collagen, but also form a stable complex with the type III collagen through ionic interaction, enhance the synergistic repair effect of the two, and significantly promote tissue regeneration and reduce scar formation.

[0026] The antibacterial drug and the healing-promoting drug are coupled to different matrix components by chemical bonds in the application, so that the mutual influence caused by the direct contact of the two active ingredients is avoided, and the drug stability is improved; meanwhile, the accurate and rapid release of the pH-sensitive antibacterial drug can rapidly control the infection, lay a foundation for the subsequent action of the healing-promoting drug, and realize the synergistic effect of antibacterial and healing promotion. In addition, the targeted release of minocycline hydrochloride can reduce the systemic exposure of the drug and reduce the risk of antibiotic resistance; the gel matrix uses sodium alginate and methacrylated chitosan with excellent biocompatibility, has no obvious biological toxicity, and improves the safety of clinical application. DETAILED DESCRIPTION

[0027] The technical solutions in the embodiments of the application will be clearly and completely described below with reference to the embodiments of the application. Obviously, the described embodiments are only part of the embodiments of the application, rather than all the embodiments of the application. Based on the embodiments in the application, all other embodiments obtained by those skilled in the art without creative labor fall within the protection scope of the application.

[0028] Embodiment one:

[0029] A segmented drug release type repair gel,

[0030] The raw material composition mass percentage is: response gel matrix: 4.0%, wherein sodium alginate 2.0% (oxidation degree 25%), methacrylated chitosan 2.0% (degree of substitution 55%)

[0031] Active pharmaceutical ingredient: 0.6%, wherein pH-sensitive antibacterial drug (minocycline hydrochloride) 0.4% (drug loading amount is 20% of the mass of sodium alginate), enzyme-sensitive healing-promoting drug (recombinant human epidermal growth factor) 0.2% (drug loading amount is 10% of the mass of methacrylated chitosan, which is included in the 2.0% of methacrylated chitosan)

[0032] Biomimetic repair component: 0.8%, wherein recombinant human type III collagen 0.5%, zinc sulfate 0.3% (mass ratio of the two is 5:3 ≈ 1.67:1, and a complex is formed through ionic interaction)

[0033] Moisturizing and stabilizing agents: 3.0%, of which glycerol 2.4%, sodium hyaluronate 0.6% (mass ratio 4:1)

[0034] The balance is water for injection.

[0035] The preparation method comprises the following steps,

[0036] Preparation of drug-loaded response matrix:

[0037] Preparation of pH-responsive drug-loaded component: 2.0 g of oxidized sodium alginate is dispersed in 100 mL of sodium acetate buffer solution with pH 5.0, after stirring and dissolving, 0.4 g of minocycline hydrochloride is added, followed by adding 0.1 g of catalyst p-toluenesulfonic acid, and reacting at 45°C for 18 hours. After the reaction is completed, the product is placed in a dialysis bag and dialyzed with deionized water for 48 hours, and the dialysate is replaced every 8 hours. After dialysis is completed, freeze-drying is performed to obtain oxidized sodium alginate with minocycline hydrochloride connected by a hydrazone bond. The product is dissolved in 40 g of water for injection, and stirred until completely dissolved to obtain solution A.

[0038] Preparation of enzyme-responsive drug-loaded component: 2.0 g of methacrylated chitosan is dissolved in 100 mL of pH 6.5 buffer solution containing 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (0.2 g) and N-hydroxysuccinimide (0.12 g), and the carboxyl group is activated at room temperature for 2 hours. 0.2 g of matrix metalloproteinase-cleavable peptide segment with an amino group is added, and the coupling reaction is continued at room temperature for 6 hours. The reaction product is purified by gel filtration chromatography, and then coupled with 0.02 g of the amino terminal of recombinant human epidermal growth factor under mild conditions at 4°C for 4 hours to obtain methacrylated chitosan with growth factor connected by a peptide segment. The product is dissolved in 40 g of water for injection, and stirred until completely dissolved to obtain solution B.

[0039] Preparation of gel premix: under light shielding conditions, slowly mix solution A with solution B, add 0.8 g of a complex of recombinant human type III collagen and zinc sulfate (previously prepared by dissolving 0.5 g of recombinant human type III collagen in 20 g of water for injection, slowly adding an aqueous solution containing 0.3 g of zinc sulfate under stirring, and freeze-drying after standing at 4°C for 3 hours to complex), and 3.0 g of a mixture of glycerol and sodium hyaluronate, and stir at 15°C for 30 minutes to form a uniform, flowable gel premix.

[0040] Photo-crosslinking solidification molding: the gel premix is directly coated on the surface of the simulated wound, and a visible light source with a wavelength of 385 nm is used for irradiation for 30 seconds to make it crosslink and solidify into a three-dimensional network gel with elasticity.

[0041] Example 2:

[0042] A segmented drug release type repair gel, the raw material composition mass percentage is response gel matrix: 3.0%, wherein oxidized sodium alginate 1.5% (oxidation degree 15%), methyl methacrylated chitosan 1.5% (degree of substitution 40%)

[0043] Active pharmaceutical ingredients: 0.5%, wherein pH-sensitive antibacterial drugs (minocycline hydrochloride) 0.3% (drug loading amount is 20% of the mass of oxidized sodium alginate), enzyme-sensitive healing-promoting drugs (recombinant human epidermal growth factor) 0.2% (drug loading amount is 13.3% of the mass of methyl methacrylated chitosan, which is included in the 1.5% of methyl methacrylated chitosan)

[0044] Bionic repair components: 0.5%, wherein recombinant human type III collagen 0.3%, zinc sulfate 0.2% (mass ratio 3:2 = 1.5:1, form a complex through ionic interaction)

[0045] Moisturizing and stabilizing agents: 2.0%, wherein glycerol 1.5%, sodium hyaluronate 0.5% (mass ratio 3:1)

[0046] The balance is water for injection.

[0047] The preparation method comprises the following steps:

[0048] Preparation of drug-loaded response matrix: 1.5g of oxidized sodium alginate is dispersed in 80mL of sodium citrate buffer solution with pH 4.5, after stirring and dissolving, 0.3g of minocycline hydrochloride is added, followed by adding 0.08g of catalyst p-toluenesulfonic acid, and reacting at 40℃ for 24 hours. After the reaction is completed, the product is placed in a dialysis bag and dialyzed with deionized water for 48 hours, and the dialysis solution is replaced every 8 hours. After dialysis is completed, freeze-drying is performed to obtain oxidized sodium alginate connected with minocycline hydrochloride through hydrazone bonds. The product is dissolved in 30g of water for injection, and stirred until completely dissolved to obtain solution A (the molar ratio of oxidized sodium alginate to minocycline hydrochloride is 1:0.8).

[0049] Preparation of enzyme-responsive drug-loaded component: 1.5g of methyl methacrylated chitosan is dissolved in 80mL of pH 6.0 buffer solution containing 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (0.15g) and N-hydroxysuccinimide (0.09g), and the carboxyl group is activated at room temperature for 2 hours. 0.18g of matrix metalloproteinase-cleavable peptide segment with amino group is added, and the coupling reaction is continued at room temperature for 8 hours. The reaction product is purified by gel filtration chromatography, and then the amino terminal of 0.02g of recombinant human epidermal growth factor is coupled again at 4℃ under mild conditions for 5 hours, to finally obtain methyl methacrylated chitosan connected with growth factor through peptide segment. The product is dissolved in 30g of water for injection, and stirred until completely dissolved to obtain solution B.

[0050] Preparation of the gel premix: Solution A was slowly mixed with Solution B under light protection, 0.5 g of the complex of recombinant human collagen type III and zinc sulfate (prepared in advance by dissolving 0.3 g of recombinant human collagen type III in 15 g of water for injection, slowly adding an aqueous solution containing 0.2 g of zinc sulfate under stirring, standing for complexation at 4 °C for 2 hours, and freeze-drying), and 2.0 g of a mixture of glycerol and sodium hyaluronate were added, and the mixture was magnetically stirred at 4 °C for 40 minutes to form a uniform, flowable gel premix.

[0051] Photocrosslinking solidification molding: The gel premix was placed in a mold, and a visible light source with a wavelength of 365 nm was used to irradiate it for 40 seconds to crosslink and solidify it into an elastic three-dimensional network gel.

[0052] Example Three;

[0053] A segmented drug release type repair gel, the raw material composition mass percentage is: response gel matrix: 6.0%, of which oxidized sodium alginate 3.0% (oxidation degree 35%), methacrylated chitosan 3.0% (degree of substitution 70%)

[0054] 0.66%, of which pH-sensitive antibacterial drug (minocycline hydrochloride) 0.6%, enzyme-sensitive healing-promoting drug 0.06%,

[0055] Revised active pharmaceutical ingredients: 0.66%, of which pH-sensitive antibacterial drug (minocycline hydrochloride) 0.6% (3.0% x 20%), enzyme-sensitive healing-promoting drug (recombinant human epidermal growth factor) 0.06% (3.0% x 2.0%), biomimetic repair component: 1.2%, of which recombinant human collagen type III 0.8%, zinc sulfate 0.4% (mass ratio of 2:1, forming a complex through ionic interaction), moisturizing and stabilizing agent: 4.0%, of which glycerol 3.33%, sodium hyaluronate 0.67% (mass ratio 5:1), the balance is water for injection.

[0056] The preparation method comprises the following steps:

[0057] Preparation of the drug-loaded response matrix:

[0058] Preparation of pH-responsive drug-loaded component: 3.0 g of oxidized sodium alginate was dispersed in 120 mL of sodium acetate buffer solution with pH 5.5, after stirring and dissolving, 0.6 g of minocycline hydrochloride was added, followed by adding 0.15 g of catalyst p-toluenesulfonic acid, and reacted at 50°C for 12 hours. After the reaction was completed, the product was placed in a dialysis bag, dialyzed with deionized water for 48 hours, and the dialysate was replaced every 8 hours. After dialysis, freeze-drying was performed to obtain oxidized sodium alginate with minocycline hydrochloride connected by a hydrazone bond. The product was dissolved in 50 g of water for injection, and stirred until completely dissolved to obtain solution A (the molar ratio of oxidized sodium alginate to minocycline hydrochloride was 1:1.2).

[0059] Preparation of enzyme-responsive drug-loaded component: 3.0 g of methacrylated chitosan was dissolved in 120 mL of a pH 7.0 buffer solution containing 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (0.3 g) and N-hydroxysuccinimide (0.18 g), and the carboxyl groups were activated by stirring at room temperature for 2 hours. 0.3 g of a matrix metalloproteinase-cleavable peptide segment with an amino group at one end was added, and the coupling reaction was continued at room temperature for 4 hours. The reaction product was purified by gel filtration chromatography, and then subjected to a second coupling with 0.06 g of the amino-terminal of recombinant human epidermal growth factor under mild conditions at 4°C for 3 hours, to finally obtain methacrylated chitosan with growth factor connected by a peptide segment. The product was dissolved in 50 g of water for injection, and stirred until completely dissolved to obtain solution B.

[0060] Preparation of gel premix: Solution A and solution B were slowly mixed under light shielding conditions, 1.2 g of a complex of recombinant human type III collagen and zinc sulfate (previously prepared by dissolving 0.8 g of recombinant human type III collagen in 30 g of water for injection, slowly adding an aqueous solution containing 0.4 g of zinc sulfate under stirring, and freeze-drying after standing at 4°C for 4 hours of complexation) and 4.0 g of a mixture of glycerol and sodium hyaluronate were added, and the gel premix was formed into a uniform and flowable gel by magnetic stirring at 25°C for 20 minutes.

[0061] Photo-crosslinking and solidification: The gel premix was directly coated on the surface of a simulated wound, and a visible light source with a wavelength of 405 nm was used for irradiation for 20 seconds to crosslink and solidify it into a three-dimensional network gel with elasticity.

[0062] It is understood that in the development of any actual implementation, as in any engineering or design project, numerous implementation-specific decisions can be made. Such development efforts might be complex and time-consuming, but would nevertheless be a routine undertaking for those of ordinary skill in the art having the benefit of this disclosure.

[0063] It should be noted that the above examples are only used to illustrate the technical solutions of the present application but not limit the present application. Although the present application is described in detail with reference to the preferred embodiments, those skilled in the art should understand that the technical solutions of the present application can be modified or equivalently replaced, without departing from the spirit and scope of the technical solutions of the present application, which should be covered in the scope of the claims of the present application.

Claims

1. A wound repair gel responsive to the microenvironment of a wound, characterized in that, The gel is prepared from raw materials including the following mass percentage components: The responsive gel matrix 3.0%-6.0%, the active pharmaceutical ingredient 0.5%-2.0%, the biomimetic repair component 0.5%-1.2%, the moisturizing and stabilizing agent 2.0%-4.0, and the balance of water for injection. The responsive gel matrix comprises oxidized sodium alginate and methacrylated chitosan, the active pharmaceutical ingredient comprises pH-sensitive antibacterial drugs and enzyme-sensitive healing drugs, and the biomimetic repair component is a complex of recombinant human collagen and zinc sulfate.

2. A wound repair gel responsive to the wound microenvironment according to claim 1, wherein, The oxidation degree of the oxidized sodium alginate in the responsive gel matrix is 15%-35%, and the mass percentage thereof is 1.5%-3.0%; the degree of substitution of the methacrylated chitosan is 40%-70%, and the mass percentage thereof is 1.5%-3.0%.

3. The wound repair gel responsive to the wound bed microenvironment according to claim 1, wherein: In the active pharmaceutical ingredient: the pH-sensitive antibacterial drug is minocycline hydrochloride connected to the molecular chain of oxidized sodium alginate through a hydrazone bond, wherein the drug loading amount of minocycline hydrochloride is 10%-20% of the mass of oxidized sodium alginate.

4. The wound repair gel responsive to the wound bed microenvironment according to claim 1, wherein: The enzyme-sensitive healing drug is recombinant human epidermal growth factor connected to methacrylated chitosan through a matrix metalloproteinase MMP-cleavable peptide segment, and the mass percentage is included in the methacrylated chitosan, wherein the drug loading amount of recombinant human epidermal growth factor is 0.5%-2.0 of the mass of methacrylated chitosan.

5. The wound repair gel responsive to the wound bed microenvironment according to claim 1, wherein: The recombinant human collagen is type III collagen, and the mass percentage thereof is 0.3%-0.8%; the mass percentage of zinc sulfate is 0.2%-0.4%, and the zinc sulfate forms a complex with the recombinant human collagen through ionic interaction.

6. The wound repair gel responsive to the wound bed microenvironment according to claim 1, wherein: The moisturizing and stabilizing agent is a mixture of glycerol and sodium hyaluronate, and the mass ratio of glycerol to sodium hyaluronate is 3:1-5:

1.

7. A process for the preparation of a segmented drug release type repair cement according to any one of claims 1 to 6, characterized in that, The method comprises the following steps: S1, preparation of a drug-loaded responsive matrix: Preparation of a pH-responsive drug-loaded component: disperse oxidized sodium alginate in a buffer solution with a pH of 4.5-5.5, add minocycline hydrochloride under stirring, then add a catalyst p-toluenesulfonic acid, react at 40-50°C for 12-24 hours, after the reaction is completed, dialyze and freeze-dry to obtain oxidized sodium alginate connected with minocycline hydrochloride through a hydrazone bond; dissolve the product in part of water for injection to obtain solution A; Preparation of an enzyme-responsive drug-loaded component: dissolve methacrylated chitosan in a pH 6.0-7.0 buffer solution containing 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide and N-hydroxysuccinimide to activate the carboxyl group; add a matrix metalloproteinase-cleavable peptide segment with an amino group at one end to perform coupling reaction; purify the reaction product, and then perform secondary coupling with the amino terminal of recombinant human epidermal growth factor under mild conditions to finally obtain methacrylated chitosan connected with the growth factor through a peptide segment; dissolve the product in another part of water for injection to obtain solution B; S2, preparation of gel premix: under light protection, the solution A is mixed with the solution B, and the mixture of glycerol and sodium hyaluronate is added, and the mixture is stirred uniformly at 4-25℃ to form a uniform and flowable gel premix; S3, photo-crosslinking solidification molding: the gel premix prepared in step S2 is placed in a mold or directly coated on a target surface, and is irradiated by a visible light source with a wavelength of 365-405 nm for 20-40 seconds to make it crosslink and solidify into an elastic three-dimensional network gel.

8. The method for preparing a segmented drug-release repair coagulant according to claim 7, characterized in that, The molar ratio of the oxidized sodium alginate to minocycline hydrochloride is 1:0.8-1.2; the buffer solution is sodium acetate buffer or sodium citrate buffer.

9. The method for preparing a segmented drug-release repair coagulant according to claim 7, characterized in that, The complex of recombinant human collagen and zinc sulfate is prepared by dissolving recombinant human type III collagen in water for injection, slowly adding a zinc sulfate solution under stirring, standing for complexation at 4℃ for 2-4 hours, and freeze-drying; wherein the mass ratio of recombinant human collagen to zinc sulfate is 1.5:1-2:1.