External use composition promoting surgical incision healing and preparation method thereof

Abstract

The present invention proposes a kind of external-use composition promoting the healing of surgical incisions and its preparation method, belong to the field of medical technology.Including component A and component B, wherein component A is powder, and is composed of banyan bark powder, Chinese medicine powder, acellular material, collagen peptide, modified nano hydroxyapatite, and mass ratio is 2 4:7 10:3 5:1 3:2 4;Component B is liquid, and is composed of carboxylated ionic liquid, chlorogenic acid / oleanolic acid chitosan, platelet-rich plasma and water, and mass ratio is 3 5:5 8:10 12:200 300. The external-use composition promoting the healing of surgical incisions obtained by the present invention has good antibacterial, antioxidant and anti-inflammatory effects, analgesic and granulogenic, hemostasis recovery, and safety is not easily sensitized, realizes slow-controlled release drug release, promotes the healing of surgical incisions, the repair of scar, with broad application prospects.

Description

Technical Field

[0001] The present invention relates to the technical field of medicine, and in particular to an external-use composition for promoting healing of surgical incisions and a preparation method thereof. Background Art

[0002] Surgical wounds are sharp wounds, characterized by a neat appearance but a deep lesion. These wounds often penetrate the entire skin layer, reaching deep into the muscle layer. In areas with thicker fat tissue, the fat tissue itself lacks the ability to heal on its own, and problems such as fat liquefaction can occur, significantly impairing wound healing. With the expansion of surgical treatment applications, surgery may be involved in the treatment of diseases in many disciplines, including orthopedics, oncology, neurology, and oral and maxillofacial surgery.

[0003] Skin wounds rely on the self-renewal of skin tissue to heal. After a wound is formed, the body initiates a healing cascade, initiating processes such as hemostasis, self-defense, epithelial cell proliferation and coverage, and wound healing. The surgical process itself also involves operations such as hemostasis and anti-infection, so the speed at which epithelial cells proliferate and cover the wound is the main factor affecting the speed of postoperative skin wound healing. This process involves angiogenesis and blood supply to the surgical wound site. Clinical observations have found that most wounds with heavy bleeding heal well, while wounds with less bleeding heal poorly or do not heal. Regarding the role of inflammatory response in wound healing, it is generally believed that a moderate inflammatory response, as a defense mechanism, is conducive to wound healing; while an excessive inflammatory response will delay wound healing.

[0004] Promoting surgical wound healing is one of the effective ways to alleviate patients' pain and reduce complications such as postoperative infection. Therefore, research on drugs that promote surgical wound healing has always been a hot topic.

[0005] Chinese invention patent CN105412980B discloses a medical adhesive for outpatient minor surgical incisions and its preparation method. The adhesive comprises the following raw materials in parts by weight: aloe vera protein, yam protein, soluble ginkgo biloba polysaccharide, polyethylene oxide aqueous solution, α-cyanoacrylate, chitosan, polyvinyl alcohol, sodium polyaldehyde alginate, pectin, gelatin, and hydrogenated camellia oil. While the adhesive has excellent adhesive properties and can disinfect and inhibit wound infection, it requires frequent application during the postoperative repair period to meet wound repair needs, making it cumbersome to use and resulting in high drug consumption. Summary of the Invention

[0006] The purpose of the present invention is to provide an external-use composition that promotes the healing of surgical incisions and a preparation method thereof, which has good antibacterial, antioxidant and anti-inflammatory effects, relieves pain and promotes tissue regeneration, stops bleeding and restores vitality, is safe and not prone to allergies, achieves sustained and controlled release of drugs, promotes the healing of surgical incisions and the repair of scars, and has broad application prospects.

[0007] The technical solution of the present invention is achieved as follows:

[0008] The invention provides a topical composition for promoting surgical incision healing, comprising a component A and a component B, wherein the component A is a powder composed of banyan bark powder, traditional Chinese medicine powder, acellular material, collagen peptide, and modified nano-hydroxyapatite, with a mass ratio of 2-4:7-10:3-5:1-3:2-4; and the component B is a liquid composed of a carboxylated ionic liquid, chlorogenic acid / oleanolic acid-loaded chitosan, platelet-rich plasma, and water, with a mass ratio of 3-5:5-8:10-12:200-300.

[0009] As a further improvement of the present invention, the Chinese medicinal powder is prepared by washing, drying, crushing and sieving Lithospermum officinale, Millettia reticulata and Achyranthes bidentata; the collagen peptide is selected from at least one of fish collagen peptide, porcine collagen peptide and bovine collagen peptide; and the carboxylated ionic liquid is selected from at least one of 1-carboxymethyl-3-methylimidazolium chloride and 1-carboxymethylpyridinium bromide.

[0010] As a further improvement of the present invention, the mass ratio of Lithospermum erythrorhizon, Millettia reticulata, and Achyranthes bidentata is 3-5:5-8:1-3, and the mesh number of the sieving sieve is 100-200 meshes.

[0011] As a further improvement of the present invention, the preparation method of the modified nano-hydroxyapatite is as follows:

[0012] S1. Nanohydroxyapatite was added to a Tris-HCl solution, dopamine hydrochloride was added, and the reaction was heated and stirred to obtain a modified material;

[0013] S2. 2-Hydroxyterephthalic acid was added to water, followed by NHS and EDC, and activated by stirring. The modified material was added, stirred for reaction, and centrifuged. The product was added to a mixed solvent of N,N-dimethylformamide and acetic acid, zirconium tetrachloride was added, and a hydrothermal reaction was performed. The reaction was centrifuged, washed, and dried to obtain the modified material UiO-66-OH@.

[0014] S3. The inorganic salt was dissolved in water, UiO-66-OH@ modified material was added, the reaction was stirred, centrifuged, washed, and dried to obtain Ag / Cu deposited UiO-66-OH@ modified material;

[0015] S4. Vascular endothelial growth factor-ɑ and fibroblast growth factor were added to water, followed by NHS and EDC, and stirred for activation. Ag / Cu was added to deposit UiO-66-OH@ modified material, and the mixture was stirred for reaction. The mixture was centrifuged, washed, and dried to obtain modified nanohydroxyapatite.

[0016] As a further improvement of the present invention, the pH value of the Tris-HCl solution in step S1 is 8.5-9.5, the mass ratio of nanohydroxyapatite and dopamine hydrochloride is 8-10:2-3, the temperature of the heating and stirring reaction is 45-55°C, and the time is 3-5h; the mass ratio of 2-hydroxyterephthalic acid, NHS, EDC and modified material in step S2 is 3-5:1-2:1-2:7-10, the mass ratio of the product and zirconium tetrachloride is 10-15:2-4, the temperature of the hydrothermal reaction is 120-130°C, and the time is 20-24h; the inorganic salt in step S3 includes silver nitrate and copper salt in a mass ratio of 3-5:2-4, the copper salt is selected from at least one of copper chloride, copper nitrate, and copper sulfate, and the mass ratio of the inorganic salt to the UiO-66-OH@ modified material is 0.5-0.9:5-7; the mass ratio of the vascular endothelial growth factor-ɑ, fibroblast growth factor, NHS, EDC and Ag / Cu deposited UiO-66-OH@ modified material in step S4 is 0.2-0.4:0.1-0.3:0.5-1:0.5-1:8-10.

[0017] As a further improvement of the present invention, the preparation method of the chlorogenic acid / oleanolic acid loaded chitosan is as follows:

[0018] T1. Dissolving chitosan in acid to obtain a chitosan solution;

[0019] T2. Add chlorogenic acid and oleanolic acid to water, add NHS and EDC, stir and activate, add chitosan solution, stir and react, dialyze, and dry to prepare chlorogenic acid / oleanolic acid-loaded chitosan.

[0020] As a further improvement of the present invention, the concentration of the chitosan solution in step T1 is 2-3wt%, and the acid solution is a 1-2wt% acetic acid or lactic acid solution; the mass ratio of chlorogenic acid, oleanolic acid, NHS, EDC and chitosan solution in step T2 is 0.5-1:0.5-1:0.3-0.5:0.3-0.5:150-200.

[0021] As a further improvement of the present invention, the preparation method of the decellularized material is as follows:

[0022] U1. The pigskin was cleaned and depilated, the dermis was taken, minced, and washed with hydrogen peroxide and alkali solution to obtain pretreated pigskin leather material;

[0023] U2. The pretreated pigskin dermis was added to saline, subjected to repeated freeze-thaw cycles, filtered, washed, and dried to obtain a preliminary decellularized material.

[0024] U3. Add the preliminary decellularized material into water, add ficin and lysozyme, perform enzymolysis, filter, wash, and dry to obtain the decellularized material.

[0025] As a further improvement of the present invention, the concentration of the hydrogen peroxide in step U1 is 28-32wt%, the concentration of the alkali solution is 8-12wt%, and the alkali is NaOH or KOH; the brine in step U2 is a NaCl solution with a concentration of 3-5wt%, and the number of repeated freeze-thaw treatments is 3-5 times; the mass ratio of the preliminary decellularized material, ficin and lysozyme in step U3 is 10:1-2:1-2, the enzymatic hydrolysis temperature is 36-40°C, and the time is 8-10h.

[0026] The present invention further protects a method for preparing the above-mentioned external-use composition for promoting healing of surgical incisions, which is characterized by comprising the following steps:

[0027] (1) Banyan bark powder, Chinese medicine powder, decellularized material, collagen peptide, and modified nano-hydroxyapatite are mixed uniformly in proportion to prepare component A;

[0028] (2) Mix the carboxylated ionic liquid, chlorogenic acid / oleanolic acid loaded chitosan, platelet-rich plasma and water in proportion to obtain component B, and store it at 2-6°C.

[0029] The present invention adopts the form of combining component A powder and component B liquid. Component A is first sprinkled on the wound, and then the component B liquid is sprayed. The modified nano-hydroxyapatite with metal ions in component A can serve as a cross-linking center point to promote the mutual cross-linking between the collagen peptide in component A and the chitosan and carboxylated ionic liquid in component B, thereby solidifying into a hydrogel state, ensuring that the component A powder will not spill, and extending the administration time.

[0030] The present invention has the following beneficial effects:

[0031] The banyan bark powder in component A of the present invention is micronized to produce a porous micropowder, exhibiting hemostatic and antibacterial properties. It effectively absorbs exudate, keeps wounds dry, and promotes wound healing. The traditional Chinese medicine powder, made from a compound of Chinese herbs including lithospermum erythrorhizon, millettia reticulata, and rhizoma achyranthis Bidentatae, clears away heat and toxins, promotes blood circulation, and removes stasis. External application can relieve pain and promote tissue regeneration, and has been extended to chronic wounds such as bedsores, accelerating wound healing and reducing scar formation.

[0032] Collagen peptides can promote the repair of surgical wounds, and their stability is enhanced after combining with the epidermal growth factor released by modified nano-hydroxyapatite, accelerating the healing of surgical incisions. At the same time, they have the advantages of high safety and non-immunogenicity.

[0033] The modified nanohydroxyapatite prepared in this invention uses nanohydroxyapatite as a carrier. After surface modification with amino groups, it is condensed with 2-hydroxyterephthalic acid and subjected to an in-situ hydrothermal reaction to produce the modified UiO-66-OH@ material. The amino and hydroxyl groups on the nanohydroxyapatite form complex bonds with metal ions Ag and Cu (Ag has antibacterial properties, and Cu ions participate in enzyme and collagen production), immobilizing the metal ions. The material then undergoes condensation coupling with vascular endothelial growth factor-ɑ and fibroblast growth factor-1. The resulting nanostructured material has a high specific surface area and good permeability, allowing it to more easily penetrate cell barriers, improving the delivery efficiency of active ingredients and enabling more precise targeting of wound sites, enhancing therapeutic efficacy. The material also slowly releases vascular endothelial growth factor-ɑ (VEGF) and fibroblast growth factor-1. Vascular endothelial growth factor-ɑ (VEGF) promotes angiogenesis, providing sufficient nutrients and oxygen for wound healing. The addition of fibroblast growth factor (FGF) stimulates fibroblast proliferation and collagen synthesis, accelerating granulation tissue formation. A variety of natural ingredients work synergistically to promote the healing of surgical incisions and the repair of scars.

[0034] The chlorogenic acid / oleanolic acid-loaded chitosan prepared by the present invention loads chlorogenic acid and oleanolic acid on chitosan through a condensation reaction between carboxyl and amino groups. It not only has good biocompatibility and excellent biodegradability, but also avoids the side effects that may be caused by traditional synthetic materials. At the same time, chlorogenic acid and oleanolic acid have good antibacterial and antioxidant properties. Oleanolic acid can promote the proliferation of fibroblasts and the synthesis of collagen, while promoting the synthesis and secretion of collagen, increasing the content of collagen in the wound, and contributing to wound contraction and tissue reconstruction. Chlorogenic acid can promote the smooth transition of wounds from the inflammatory phase to the proliferative phase by inhibiting the inflammatory response. The two have a synergistic effect and promote wound healing.

[0035] Platelet-rich plasma contains a variety of growth factors and bioactive substances, including platelet-derived growth factor (PDGF), transforming growth factor-β (TGF-β), epidermal growth factor (EGF), vascular endothelial growth factor-ɑ (VEGF) and other growth factors. It can bind to receptors on the surface of target cells, activate intracellular signal transduction pathways, and promote the proliferation and differentiation of various wound healing-related cells such as fibroblasts, endothelial cells, and keratinocytes.

[0036] In the present invention, the carboxylated ionic liquid and the chlorogenic acid / oleanolic acid loaded chitosan are combined and cross-linked to form a hydrogel under the action of metal ions, thereby improving drug stability and skin permeability, achieving the combined functions of anti-inflammatory, antibacterial and healing-promoting, improving drug solubility and release characteristics, prolonging the local action time, and having pH responsiveness. The molecular chain contains a large number of amino groups (-NH2). Under acidic conditions, the amino groups are easily protonated to form positively charged ammonium ions (-NH3+ ), increases the polymer's hydrophilicity, while the electrostatic repulsion generated by ionization stretches the molecular chains, causing the material to swell. In a neutral or alkaline environment, the ammonium ions deprotonate and return to amino groups, weakening the electrostatic repulsion between the molecular chains and causing the material to shrink. During the inflammatory phase of a wound, the microenvironment becomes acidic, allowing the hydrogel to release more drugs or active ingredients, exerting antibacterial and anti-inflammatory effects. As the wound heals, the microenvironment becomes neutral, slowing the release rate and avoiding drug waste and side effects. Furthermore, the imidazole group of the carboxylated ionic liquid exhibits a quaternary ammonium salt structure, which has excellent antibacterial properties and prevents wound infection.

[0037] The acellular material prepared by the present invention provides an ideal microenvironment for cell adhesion, proliferation and differentiation. By constructing a three-dimensional structure similar to the extracellular matrix, the composition can better interact with wound tissue and guide cell migration and tissue repair. For example, the use of hydrogel materials, whose porous structure can simulate the spatial structure of the extracellular matrix, promotes cell growth and tissue reconstruction. Under the synergistic effect of high osmotic pressure and repeated freezing and thawing, the acellular material of the present invention destroys the cell structure and promotes the release of cell components, thereby improving the decellularization effect. The hypertonic solution treats the tissue, causing the cells to swell or shrink and rupture due to osmotic pressure imbalance. Repeated rinsing with physiological saline combined with hypotonic solution treatment can effectively remove cell components. The freeze-thaw cycle forms ice crystals in the cells through repeated freezing and melting, destroying the cell membrane and organelles, thereby achieving the purpose of decellularization. It is commonly used to treat tissues such as skin and blood vessels. Further, under the action of ficin and lysozyme, the cell components are further removed and a good deantigenization effect is played, making the prepared acellular material safe and not easy to cause allergies.

[0038] The external-use composition for promoting surgical wound healing prepared by the present invention has good antibacterial, antioxidant and anti-inflammatory effects, relieves pain, promotes tissue regeneration, stops bleeding and restores vitality, is safe and not prone to allergies, realizes slow and controlled drug release, promotes surgical incision healing and scar repair, and has broad application prospects. DETAILED DESCRIPTION

[0039] The following is a clear and complete description of the technical solutions in the embodiments of the present invention. Obviously, the embodiments described are only some embodiments of the present invention, not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making any creative efforts are within the scope of protection of the present invention.

[0040] The particle size of nanohydroxyapatite ranges from 300 to 600 nm. Ficin, 1.2 million U / g; lysozyme, 20,000 U / g. NHS, N-hydroxysuccinimide; EDC, 1-ethyl-(3-dimethylaminopropyl)carbodiimide. UiO-66-NH2 was prepared using conventional methods. References include: Duan Zhanggui et al., Preparation of UiO-66-NH2-supported Copper Catalyst and Its Catalytic Oxidation of Alcohols [J]. Journal of Inorganic Chemistry, 2024, 40(3): 496-506.

[0041] Preparation Example 1 Preparation of Chinese medicine powder

[0042] Wash and dry 3g of Lithospermum erythrorhizon, 5g of Millettia reticulata, and 1g of Achyranthes bidentata, grind them, and pass them through a 100-mesh sieve to prepare Chinese medicine powder.

[0043] Preparation Example 2 Preparation of Chinese medicine powder

[0044] Wash and dry 5g of Lithospermum erythrorhizon, 8g of Millettia reticulata, and 3g of Achyranthes bidentata, grind them, and pass them through a 200-mesh sieve to prepare Chinese medicine powder.

[0045] Preparation Example 3 Preparation of Chinese medicine powder

[0046] Wash and dry 4g of Lithospermum erythrorhizon, 6g of Millettia reticulata, and 2g of Achyranthes bidentata, grind them, and pass them through a 150-mesh sieve to prepare Chinese medicine powder.

[0047] Preparation Example 4 Preparation of modified nanohydroxyapatite

[0048] Here’s how:

[0049] S1. 8 g of nanohydroxyapatite was added to 200 mL of Tris-HCl solution (pH 8.5), followed by 2 g of dopamine hydrochloride. The mixture was heated to 45°C and stirred for 3 h to obtain a modified material.

[0050] S2. 3 g of 2-hydroxyterephthalic acid was added to 200 mL of water, followed by 1 g of NHS and 1 g of EDC. The mixture was stirred and activated for 30 minutes. 7 g of the modified material was added, stirred and reacted for 10 hours, and centrifuged to obtain the product. 10 g of the product was added to 4 L of a mixed solvent of N,N-dimethylformamide and acetic acid (volume ratio of 39:1), and 2 g of zirconium tetrachloride was added. The mixture was hydrothermally reacted at 120°C for 20 hours, centrifuged, washed, and dried to obtain the UiO-66-OH@ modified material.

[0051] S3. Dissolve 0.5 g of inorganic salt in 100 mL of water, add 5 g of UiO-66-OH@ modified material, stir and react for 30 min, centrifuge, wash, and dry to obtain Ag / Cu deposited UiO-66-OH@ modified material;

[0052] The inorganic salt includes silver nitrate and copper sulfate in a mass ratio of 3:2;

[0053] S4. 0.2 g of vascular endothelial growth factor-ɑ and 0.1 g of fibroblast growth factor 1 were added to 100 mL of water, followed by 0.5 g of NHS and 0.5 g of EDC. The mixture was stirred and activated for 40 min. 8 g of Ag / Cu was added to deposit the modified material, UiO-66-OH@, and the reaction was stirred for 12 h. The modified nanohydroxyapatite was obtained by centrifugation, washing, and drying.

[0054] Preparation Example 5 Preparation of modified nanohydroxyapatite

[0055] Here’s how:

[0056] S1. Add 10 g of nanohydroxyapatite to 200 mL of Tris-HCl solution (pH 9.5), add 3 g of dopamine hydrochloride, heat to 55°C, and stir for 5 h to obtain a modified material.

[0057] S2. 5 g of 2-hydroxyterephthalic acid was added to 200 mL of water, followed by 2 g of NHS and 2 g of EDC. The mixture was stirred and activated for 30 minutes. 10 g of the modified material was added, stirred and reacted for 10 hours, and centrifuged to obtain the product. 15 g of the product was added to 4 L of a mixed solvent of N,N-dimethylformamide and acetic acid (volume ratio of 39:1), and 4 g of zirconium tetrachloride was added. The mixture was hydrothermally reacted at 130°C for 24 hours, centrifuged, washed, and dried to obtain the UiO-66-OH@ modified material.

[0058] S3. Dissolve 0.9 g of inorganic salt in 100 mL of water, add 7 g of UiO-66-OH@ modified material, stir and react for 30 min, centrifuge, wash, and dry to obtain Ag / Cu deposited UiO-66-OH@ modified material;

[0059] The inorganic salts include silver nitrate and copper nitrate in a mass ratio of 5:4;

[0060] S4. 0.4 g of vascular endothelial growth factor-ɑ and 0.3 g of fibroblast growth factor 1 were added to 100 mL of water, followed by 1 g of NHS and 1 g of EDC. The mixture was stirred and activated for 40 min. Then, 10 g of Ag / Cu was added to deposit the modified material, UiO-66-OH@, and the reaction was stirred for 12 h. The modified nanohydroxyapatite was obtained by centrifugation, washing, and drying.

[0061] Preparation Example 6 Preparation of modified nanohydroxyapatite

[0062] Here’s how:

[0063] S1. 9 g of nanohydroxyapatite was added to 200 mL of Tris-HCl solution (pH 9), followed by 2.5 g of dopamine hydrochloride. The mixture was heated to 50°C and stirred for 4 h to obtain a modified material.

[0064] S2. 4 g of 2-hydroxyterephthalic acid was added to 200 mL of water, along with 1.5 g of NHS and 1.5 g of EDC. The mixture was stirred and activated for 30 minutes. 8 g of the modified material was added, stirred and reacted for 10 hours, and centrifuged to obtain the product. 12 g of the product was added to 4 L of a mixed solvent of N,N-dimethylformamide and acetic acid (volume ratio of 39:1), along with 3 g of zirconium tetrachloride. The mixture was hydrothermally reacted at 125°C for 22 hours, centrifuged, washed, and dried to obtain the UiO-66-OH@ modified material.

[0065] S3. Dissolve 0.7 g of inorganic salt in 100 mL of water, add 6 g of UiO-66-OH@ modified material, stir and react for 30 min, centrifuge, wash, and dry to obtain Ag / Cu deposited UiO-66-OH@ modified material;

[0066] The inorganic salt includes silver nitrate and copper chloride in a mass ratio of 4:3;

[0067] S4. 0.3 g of vascular endothelial growth factor-ɑ and 0.2 g of fibroblast growth factor 1 were added to 100 mL of water, followed by 0.7 g of NHS and 0.7 g of EDC. The mixture was stirred and activated for 40 min. Then, 9 g of Ag / Cu was added to deposit the modified material, UiO-66-OH@, and the reaction was stirred for 12 h. The modified nanohydroxyapatite was obtained by centrifugation, washing, and drying.

[0068] Comparative Preparation Example 1

[0069] Compared with Preparation Example 6, the difference is that step S2 is not performed.

[0070] The details are as follows:

[0071] S1. 9 g of nanohydroxyapatite was added to 200 mL of Tris-HCl solution (pH 9), followed by 2.5 g of dopamine hydrochloride. The mixture was heated to 50°C and stirred for 4 h to obtain a modified material.

[0072] S2. 0.7 g of an inorganic salt was dissolved in 100 mL of water, 6 g of the modified material was added, the reaction was stirred for 30 min, centrifuged, washed, and dried to obtain an Ag / Cu deposition modified material;

[0073] The inorganic salt includes silver nitrate and copper chloride in a mass ratio of 4:3;

[0074] S3. Add 0.3 g of vascular endothelial growth factor-ɑ and 0.2 g of fibroblast growth factor 1 to 100 mL of water, add 0.7 g of NHS and 0.7 g of EDC, and stir and activate for 40 minutes. Then add 9 g of Ag / Cu deposition modification material, stir and react for 12 hours, centrifuge, wash, and dry to obtain modified nanohydroxyapatite.

[0075] Comparative Preparation Example 2

[0076] Compared with Preparation Example 6, the difference is that silver nitrate is not added in step S3.

[0077] The details are as follows:

[0078] S3. Dissolve 0.7 g of copper chloride in 100 mL of water, add 6 g of UiO-66-OH@ modified material, and stir for 30 min. Centrifuge, wash, and dry to obtain Ag / Cu-deposited UiO-66-OH@ modified material.

[0079] Comparative Preparation Example 3

[0080] Compared with Preparation Example 6, the difference is that copper chloride is not added in step S3.

[0081] The details are as follows:

[0082] S3. Dissolve 0.7 g of silver nitrate in 100 mL of water, add 6 g of UiO-66-OH@ modified material, stir and react for 30 min, centrifuge, wash, and dry to obtain Ag / Cu deposited UiO-66-OH@ modified material.

[0083] Comparative Preparation Example 4

[0084] Compared with Preparation Example 6, the difference is that step S3 is not performed.

[0085] The details are as follows:

[0086] S1. 9 g of nanohydroxyapatite was added to 200 mL of Tris-HCl solution (pH 9), followed by 2.5 g of dopamine hydrochloride. The mixture was heated to 50°C and stirred for 4 h to obtain a modified material.

[0087] S2. 4 g of 2-hydroxyterephthalic acid was added to 200 mL of water, along with 1.5 g of NHS and 1.5 g of EDC. The mixture was stirred and activated for 30 minutes. 8 g of the modified material was added, stirred and reacted for 10 hours, and centrifuged to obtain the product. 12 g of the product was added to 4 L of a mixed solvent of N,N-dimethylformamide and acetic acid (volume ratio of 39:1), along with 3 g of zirconium tetrachloride. The mixture was hydrothermally reacted at 125°C for 22 hours, centrifuged, washed, and dried to obtain the UiO-66-OH@ modified material.

[0088] S3. Add 0.3 g of vascular endothelial growth factor-ɑ and 0.2 g of fibroblast growth factor 1 to 100 mL of water, add 0.7 g of NHS and 0.7 g of EDC, and stir and activate for 40 minutes. Then add 9 g of UiO-66-OH@ modified material and stir and react for 12 hours. Centrifuge, wash, and dry to obtain modified nanohydroxyapatite.

[0089] Comparative Preparation Example 5

[0090] Compared with Preparation Example 6, the difference is that step S4 is not performed.

[0091] The details are as follows:

[0092] S1. 9 g of nanohydroxyapatite was added to 200 mL of Tris-HCl solution (pH 9), followed by 2.5 g of dopamine hydrochloride. The mixture was heated to 50°C and stirred for 4 h to obtain a modified material.

[0093] S2. 4 g of 2-hydroxyterephthalic acid was added to 200 mL of water, along with 1.5 g of NHS and 1.5 g of EDC. The mixture was stirred and activated for 30 minutes. 8 g of the modified material was added, stirred and reacted for 10 hours, and centrifuged to obtain the product. 12 g of the product was added to 4 L of a mixed solvent of N,N-dimethylformamide and acetic acid (volume ratio of 39:1), along with 3 g of zirconium tetrachloride. The mixture was hydrothermally reacted at 125°C for 22 hours, centrifuged, washed, and dried to obtain the UiO-66-OH@ modified material.

[0094] S3. Dissolve 0.7 g of inorganic salt in 100 mL of water, add 6 g of UiO-66-OH@ modified material, stir and react for 30 min, centrifuge, wash, and dry to obtain Ag / Cu deposited UiO-66-OH@ modified material, which is modified nanohydroxyapatite;

[0095] The inorganic salt includes silver nitrate and copper chloride in a mass ratio of 4:3.

[0096] Preparation Example 7 Preparation of Chlorogenic Acid / Oleanolic Acid-Loaded Chitosan

[0097] Here’s how:

[0098] T1. Chitosan was dissolved in 1wt% acetic acid solution to obtain a 2wt% chitosan solution;

[0099] T2. Add 0.5 g of chlorogenic acid and 0.5 g of oleanolic acid to 50 mL of water, then add 0.3 g of NHS and 0.3 g of EDC. Stir and activate for 30 minutes. Then add 150 g of chitosan solution, stir and react for 8 hours, dialyze, and dry to obtain chlorogenic acid / oleanolic acid-loaded chitosan.

[0100] Preparation Example 8 Preparation of Chlorogenic Acid / Oleanolic Acid-Loaded Chitosan

[0101] Here’s how:

[0102] T1 chitosan was dissolved in 2wt% lactic acid solution to obtain a 3wt% chitosan solution;

[0103] T2. Add 1g of chlorogenic acid and 1g of oleanolic acid to 50mL of water, then add 0.5g of NHS and 0.5g of EDC. Stir and activate for 30 minutes. Then add 200g of chitosan solution and stir for 8 hours. Then dialyze and dry to obtain chlorogenic acid / oleanolic acid-loaded chitosan.

[0104] Preparation Example 9 Preparation of Chlorogenic Acid / Oleanolic Acid-Loaded Chitosan

[0105] Here’s how:

[0106] T1. Chitosan was dissolved in 1.2wt% acetic acid solution to obtain a 2.5wt% chitosan solution;

[0107] T2. Add 0.8 g of chlorogenic acid and 0.7 g of oleanolic acid to 50 mL of water, then add 0.4 g of NHS and 0.4 g of EDC. Stir and activate for 30 minutes. Then add 170 g of chitosan solution and stir for 8 hours. Then dialyze and dry to obtain chlorogenic acid / oleanolic acid-loaded chitosan.

[0108] Comparative Preparation Example 6

[0109] Compared with Preparation Example 9, the difference is that chlorogenic acid is not added in Step T2.

[0110] The details are as follows:

[0111] T1. Chitosan was dissolved in 1.2wt% acetic acid solution to obtain a 2.5wt% chitosan solution;

[0112] T2. Add 1.5 g of oleanolic acid to 50 mL of water, add 0.4 g of NHS, and 0.4 g of EDC, stir and activate for 30 minutes, then add 170 g of chitosan solution, stir and react for 8 hours, dialyze, and dry to obtain oleanolic acid-loaded chitosan.

[0113] Comparative Preparation Example 7

[0114] Compared with Preparation Example 9, the difference is that oleanolic acid is not added in step T2.

[0115] The details are as follows:

[0116] T1. Chitosan was dissolved in 1.2wt% acetic acid solution to obtain a 2.5wt% chitosan solution;

[0117] T2. Add 1.5 g of chlorogenic acid to 50 mL of water, add 0.4 g of NHS, and 0.4 g of EDC, stir and activate for 30 minutes, then add 170 g of chitosan solution, stir and react for 8 hours, dialyze, and dry to obtain chlorogenic acid-loaded chitosan.

[0118] Comparative Preparation Example 8

[0119] Compared with Preparation Example 9, the difference is that step T2 is not performed.

[0120] The details are as follows:

[0121] T1. Dissolve chitosan in 1.2 wt % acetic acid solution to obtain a 2.5 wt % chitosan solution.

[0122] Preparation Example 10 Preparation of complex enzyme

[0123] The method is as follows: 1g of ficin and 1g of lysozyme are added to 100mL of water, 0.5g of NHS and 0.5g of EDC are added, and the mixture is stirred and activated for 30min. 5g of UiO-66-NH2 is added, and the mixture is stirred and reacted for 12h. The mixture is then centrifuged, washed, and dried. The product is subjected to a high-pressure treatment at 200MPa for 15min to obtain a composite enzyme.

[0124] The composite enzyme prepared by the present invention dehydrates and condenses ficin and lysozyme and fixes them on UiO-66-NH2, greatly increasing the sites of the enzyme catalytic reaction, shortening the catalytic reaction distance, accelerating the reaction rate, and reducing the reaction activation energy, thereby enabling a short-time reaction at room temperature. Moreover, after ultrahigh pressure treatment, the hydrophobic part structure of the enzyme is exposed and the conformation is changed. No chemical reagents are added, which significantly improves the catalytic efficiency of the enzyme. At the same time, the composite enzyme is safe and non-toxic, reduces the use and emission of chemical substances, and is more environmentally friendly.

[0125] Preparation Example 11 Preparation of decellularized material

[0126] Here’s how:

[0127] U1 The pigskin was cleaned and depilated, the dermis was taken, minced, and washed with 28wt% hydrogen peroxide and 8wt% NaOH solution to obtain pretreated pigskin leather material;

[0128] U2. 10 g of pretreated pigskin leather was added to 100 mL of a 3 wt% NaCl solution and frozen and thawed three times, filtered, washed, and dried to obtain a preliminary decellularized material.

[0129] U3. Add 10 g of the preliminary decellularized material to 200 mL of water, add 1 g of ficin and 1 g of lysozyme, and incubate at 36°C for 8 h. Filter, wash, and dry to obtain the decellularized material.

[0130] Preparation Example 12 Preparation of decellularized material

[0131] Here’s how:

[0132] U1 The pigskin was cleaned and depilated, the dermis was taken, minced, and washed with 32wt% hydrogen peroxide and 12wt% KOH solution to obtain pretreated pigskin leather material;

[0133] U2. 10 g of pretreated pigskin leather was added to 100 mL of a 5 wt% NaCl solution and frozen and thawed five times, filtered, washed, and dried to obtain a preliminary decellularized material.

[0134] U3. Add 10 g of the preliminary decellularized material to 200 mL of water, add 2 g of ficin and 2 g of lysozyme, and hydrolyze at 40°C for 10 h. Filter, wash, and dry to obtain the decellularized material.

[0135] Preparation Example 13 Preparation of decellularized material

[0136] Here’s how:

[0137] U1 The pigskin was cleaned and depilated, the dermis was taken, minced, and washed with 30wt% hydrogen peroxide and 10wt% NaOH solution to obtain pretreated pigskin leather material;

[0138] U2. 10 g of pretreated pigskin leather was added to 100 mL of a 4 wt% NaCl solution and frozen and thawed four times, filtered, washed, and dried to obtain a preliminary decellularized material.

[0139] U3. Add 10 g of the preliminary decellularized material to 200 mL of water, add 1.5 g of ficin and 1.5 g of lysozyme, and incubate at 37°C for 9 h. Filter, wash, and dry to obtain the decellularized material.

[0140] Preparation Example 14 Preparation of decellularized material

[0141] Here’s how:

[0142] U1 The pigskin was cleaned and depilated, the dermis was taken, minced, and washed with 30wt% hydrogen peroxide and 10wt% NaOH solution to obtain pretreated pigskin leather material;

[0143] U2. 10 g of pretreated pigskin leather was added to 100 mL of a 4 wt% NaCl solution and frozen and thawed four times, filtered, washed, and dried to obtain a preliminary decellularized material.

[0144] U3. Add 10 g of the preliminary decellularized material to 200 mL of water, add 3 g of the complex enzyme prepared in Preparation Example 10, and perform enzymatic hydrolysis at room temperature for 1 h. Filter, wash, and dry to obtain a decellularized material.

[0145] Comparative Preparation Example 9

[0146] Compared with Preparation Example 14, the difference is that step U2 is not performed.

[0147] The details are as follows:

[0148] U1 The pigskin was cleaned and depilated, the dermis was taken, minced, and washed with 30wt% hydrogen peroxide and 10wt% NaOH solution to obtain pretreated pigskin leather material;

[0149] U2. 10 g of pretreated pigskin leather was added to 200 mL of water, and 3 g of the complex enzyme prepared in Preparation Example 10 was added. The mixture was enzymatically hydrolyzed at room temperature for 1 h, filtered, washed, and dried to obtain a decellularized material.

[0150] Comparative Preparation Example 10

[0151] Compared with Preparation Example 14, the difference is that step U3 is not performed.

[0152] The details are as follows:

[0153] U1 The pigskin was cleaned and depilated, the dermis was taken, minced, and washed with 30wt% hydrogen peroxide and 10wt% NaOH solution to obtain pretreated pigskin leather material;

[0154] U2. Add 10 g of pretreated pigskin dermis to 100 mL of 4 wt% NaCl solution and freeze-thaw four times. Filter, wash, and dry to obtain a preliminary decellularized material.

[0155] Test Example 1

[0156] The decellularized materials prepared in Preparation Examples 11-14 and Comparative Preparation Examples 9-10 were subjected to performance tests.

[0157] The materials were subjected to cytotoxicity tests according to GB / T 16886.5-2017. The results are shown in Table 1.

[0158] Table 1

[0159]

[0160] It can be seen from the above table that the decellularized materials prepared in Preparation Examples 11-14 of the present invention have low cytotoxicity.

[0161] Referring to the method in YY / T1465.2-2016, SPF-grade BALB / c mice were selected and randomly divided into a negative control group, a positive control (BSA) group, preparation examples 11-14 groups, and comparative preparation examples 9-10 groups, with 10 mice in each group. The mice were killed and samples were collected at the 4th week after implantation.

[0162] Experimental sample group: 30 mg of sample was implanted subcutaneously on the back of mice in the experimental group.

[0163] Negative control group: The animals underwent the same surgical procedures as the experimental group, but no product was implanted.

[0164] Positive control (BSA) group: BSA (bovine serum albumin) was used as a positive control. 3 mg of BSA was mixed with 9 mL of phosphate-buffered saline (PBS), and then mixed with complete Freund's adjuvant (CFA) at a volume ratio of 1:1 to form an emulsion. Each animal was subcutaneously injected with 0.12 mL once a week for a total of 4 immunizations.

[0165] Four weeks later, mice were sacrificed, and blood was collected from the heart. After standing at room temperature for 30 minutes, the blood was centrifuged at 600 × g for 20 minutes, and serum was collected, aliquoted, and stored at −20°C. Serum IgG, IgM, and complement C3a levels were measured using the mouse IgG ELISA kit, mouse IgM ELISA kit, and mouse complement C3a ELISA kit, respectively.

[0166] The results are shown in Table 2.

[0167] Table 2

[0168]

[0169] As can be seen from the above table, the immunogenicity of the acellular materials prepared in Preparation Examples 11-14 of the present invention is relatively low. Example 1

[0170] This embodiment provides a topical composition for promoting the healing of surgical incisions.

[0171] The preparation method comprises the following steps:

[0172] (1) 2 g of banyan bark powder (100 mesh), 7 g of the Chinese medicinal powder prepared in Preparation Example 1, 3 g of the decellularized material prepared in Preparation Example 11, 1 g of fish collagen peptide, and 2 g of the modified nano-hydroxyapatite prepared in Preparation Example 4 were mixed uniformly to prepare component A;

[0173] 3 g of 1-carboxymethyl-3-methylimidazolium chloride, 5 g of chlorogenic acid / oleanolic acid-loaded chitosan prepared in Preparation Example 7, 10 g of platelet-rich plasma and 200 g of water were mixed to prepare component B, which was stored at 4°C. Example 2

[0174] This embodiment provides a topical composition for promoting the healing of surgical incisions.

[0175] The preparation method comprises the following steps:

[0176] (1) 4 g of banyan bark powder (100 mesh), 10 g of the Chinese medicinal powder prepared in Preparation Example 2, 5 g of the decellularized material prepared in Preparation Example 12, 3 g of fish collagen peptide, and 4 g of the modified nano-hydroxyapatite prepared in Preparation Example 5 were mixed uniformly to prepare component A;

[0177] (2) 5 g of 1-carboxymethyl-3-methylimidazolium chloride, 8 g of chlorogenic acid / oleanolic acid-loaded chitosan prepared in Preparation Example 8, 12 g of platelet-rich plasma, and 300 g of water were mixed to obtain component B, which was stored at 4°C. Example 3

[0178] This embodiment provides a topical composition for promoting the healing of surgical incisions.

[0179] The preparation method comprises the following steps:

[0180] (1) 3 g of banyan bark powder (100 mesh), 8 g of the Chinese medicinal powder prepared in Preparation Example 3, 4 g of the decellularized material prepared in Preparation Example 13, 2 g of fish collagen peptide, and 3 g of the modified nano-hydroxyapatite prepared in Preparation Example 6 were mixed uniformly to prepare component A;

[0181] (2) 4 g of 1-carboxymethyl-3-methylimidazolium chloride, 7 g of chlorogenic acid / oleanolic acid-loaded chitosan prepared in Preparation Example 9, 11 g of platelet-rich plasma, and 250 g of water were mixed to obtain component B, which was stored at 4°C. Example 4

[0182] Compared with Example 3, the difference is that the decellularized material is prepared by Preparation Example 14.

[0183] Comparative Example 1

[0184] Compared with Example 3, the difference is that the modified nano-hydroxyapatite is prepared by Comparative Preparation Example 1.

[0185] Comparative Example 2

[0186] Compared with Example 3, the difference is that the modified nano-hydroxyapatite is prepared by Comparative Preparation Example 2.

[0187] Comparative Example 3

[0188] Compared with Example 3, the difference is that the modified nano-hydroxyapatite is prepared by Comparative Preparation Example 3.

[0189] Comparative Example 4

[0190] Compared with Example 3, the difference is that the modified nano-hydroxyapatite is prepared by Comparative Preparation Example 4.

[0191] Comparative Example 5

[0192] Compared with Example 3, the difference is that the modified nano-hydroxyapatite is prepared by Comparative Preparation Example 5.

[0193] Comparative Example 6

[0194] Compared with Example 3, the difference is that the chlorogenic acid / oleanolic acid loaded chitosan is prepared by Comparative Preparation Example 6.

[0195] Comparative Example 7

[0196] Compared with Example 3, the difference is that the chlorogenic acid / oleanolic acid loaded chitosan is prepared by Comparative Preparation Example 7.

[0197] Comparative Example 8

[0198] Compared with Example 3, the difference is that the chlorogenic acid / oleanolic acid loaded chitosan is prepared by Comparative Preparation Example 8.

[0199] Comparative Example 9

[0200] Compared with Example 3, the difference is that the decellularized material is prepared by Comparative Preparation Example 9.

[0201] Comparative Example 10

[0202] Compared with Example 3, the difference is that the decellularized material is prepared by Comparative Preparation Example 10.

[0203] Comparative Example 11

[0204] Compared with Example 3, the difference is that 1-carboxymethyl-3-methylimidazolium chloride is not added.

[0205] Comparative Example 12

[0206] Compared with Example 3, the difference is that chlorogenic acid / oleanolic acid-loaded chitosan is not added.

[0207] Test Example 2

[0208] SPF-grade NIH male mice were divided into 18 groups, with distilled water as the negative control group, fluocinonide ointment as the positive control group, and the topical compositions for promoting surgical incision healing prepared in Examples 1-4 and Comparative Examples 1-12 as test groups 1-4 and comparison groups 1-12.

[0209] Each mouse's right auricle was inflamed by evenly applying xylene (100 μL / mouse). The left ear remained untreated as a blank control. 30 minutes after xylene induction, all animals in the negative control group received the corresponding test compound (0.05 g / mouse of component A) in the right ear, followed by an even spray of 0.5 mL / mouse of component B). During administration, care was taken to ensure that the gel was evenly applied to both the inner and outer surfaces of the right auricle during initial gel formation. The negative control group received distilled water (0.1 mL / mouse). One hour after test compound administration, the animals were sacrificed by cervical dislocation, and both auricles were excised. The test compound on the right auricle was washed with saline and dried. The auricles were overlapped, and the left and right ear pieces were punched out using an 8 mm diameter punch. The pieces were weighed, and the swelling value was calculated. A lower swelling value indicates a greater anti-inflammatory effect.

[0210] Swelling value = m 右耳耳片 -m 左耳耳片

[0211] The results are shown in Table 3.

[0212] Table 3

[0213]

[0214] Note: Compared with the negative control group, **P<0.01, *P<0.05.

[0215] As can be seen from the above table, the external-use compositions for promoting surgical wound healing prepared in Examples 1-4 of the present invention have good anti-inflammatory effects.

[0216] Test Example 3

[0217] Balb / c mice were randomly divided into 17 groups, each with 10 mice, including a control group (PBS solution), Example 1-4 groups, and Comparative Example 1-12 groups. The mice were anesthetized intraperitoneally with 1% sodium pentobarbital. The backs of the mice were depilated, rinsed with warm saline, dried, and disinfected with iodine tincture. A full-thickness skin section with a diameter of approximately 1 cm was cut from the back of the mice to prepare a wound model. 100 μL of Escherichia coli (ATCC25922) dissolved in saline at a density of 2×10 6 cfu / mL, inoculated onto skin wounds. One day after infection, the control group and each experimental group were treated with a topical composition for promoting surgical wound healing. The composition was applied to the wound surface on the back by sprinkling 0.1g / animal of Component A on the test site, followed by evenly spraying 1mL / animal of Component B. The wound healing area and healing time were observed and recorded on days 0 and 14 after wounding. The wound healing rate was calculated according to the following formula, and the wound healing rate was evaluated.

[0218] Wound healing rate = (wound area on day 0 - area after day 14) / wound area on day 0 × 100%.

[0219] The results are shown in Table 4.

[0220] Table 4

[0221]

[0222] It can be seen from the above table that the external-use compositions for promoting surgical incision healing prepared in Examples 1-4 of the present invention can significantly promote wound healing.

[0223] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the scope of protection of the present invention.

Claims

1. A topical composition for promoting healing of surgical incisions, characterized in that: The invention comprises a component A and a component B, wherein the component A is a powder composed of banyan bark powder, traditional Chinese medicine powder, acellular material, collagen peptide, and modified nanohydroxyapatite, with a mass ratio of 2-4:7-10:3-5:1-3:2-4; the component B is a liquid composed of a carboxylated ionic liquid, chlorogenic acid / oleanolic acid-loaded chitosan, platelet-rich plasma, and water, with a mass ratio of 3-5:5-8:10-12:200-300; the traditional Chinese medicine powder is prepared by washing and drying lithospermum erythrorhizon, millettia reticulata, and rhizoma achyranthis Bidentatae, crushing, and sieving; the carboxylated ionic liquid is selected from at least one of 1-carboxymethyl-3-methylimidazolium chloride and 1-carboxymethylpyridinium bromide; The preparation method of the modified nano-hydroxyapatite is as follows: S1. Nanohydroxyapatite was added to a Tris-HCl solution, dopamine hydrochloride was added, and the reaction was heated and stirred to obtain a modified material; S2. 2-Hydroxyterephthalic acid was added to water, followed by NHS and EDC, and activated by stirring. The modified material was added, stirred for reaction, and centrifuged. The product was added to a mixed solvent of N,N-dimethylformamide and acetic acid, zirconium tetrachloride was added, and a hydrothermal reaction was performed. The reaction was centrifuged, washed, and dried to obtain the modified material UiO-66-OH@. S3. The inorganic salt was dissolved in water, UiO-66-OH@ modified material was added, the reaction was stirred, centrifuged, washed, and dried to obtain Ag / Cu deposited UiO-66-OH@ modified material; S4. Vascular endothelial growth factor-ɑ and fibroblast growth factor were added to water, followed by NHS and EDC, and the mixture was stirred for activation. Ag / Cu was then added to deposit the modified material UiO-66-OH@. The mixture was stirred for reaction, centrifuged, washed, and dried to obtain modified nanohydroxyapatite. The preparation method of the decellularized material is as follows: U1. The pigskin was cleaned and depilated, the dermis was taken, minced, and washed with hydrogen peroxide and alkali solution to obtain pretreated pigskin leather material; U2. The pretreated pigskin dermis was added to saline, subjected to repeated freeze-thaw cycles, filtered, washed, and dried to obtain a preliminary decellularized material. U3. Add the preliminary decellularized material into water, add ficin and lysozyme, perform enzymolysis, filter, wash, and dry to obtain the decellularized material.

2. The external-use composition for promoting surgical wound healing according to claim 1, characterized in that The collagen peptide is selected from at least one of fish collagen peptide, porcine collagen peptide and bovine collagen peptide.

3. The external-use composition for promoting surgical wound healing according to claim 1, characterized in that The mass ratio of the lithospermum officinale, Millettia reticulata and Achyranthes bidentata is 3-5:5-8:1-3, and the mesh number of the sieving sieve is 100-200 meshes.

4. The external-use composition for promoting surgical wound healing according to claim 1, characterized in that The pH value of the Tris-HCl solution in step S1 is 8.5-9.5, the mass ratio of nanohydroxyapatite to dopamine hydrochloride is 8-10:2-3, the temperature of the heating and stirring reaction is 45-55°C, and the time is 3-5 hours; the mass ratio of 2-hydroxyterephthalic acid, NHS, EDC and modified material in step S2 is 3-5:1-2:1-2:7-10, the mass ratio of the product to zirconium tetrachloride is 10-15:2-4, the temperature of the hydrothermal reaction is 120-130°C, and the time is 20-24 hours. ; The inorganic salt in step S3 includes silver nitrate and copper salt in a mass ratio of 3-5:2-4, the copper salt is selected from at least one of copper chloride, copper nitrate, and copper sulfate, and the mass ratio of the inorganic salt to the UiO-66-OH@ modified material is 0.5-0.9:5-7; the mass ratio of vascular endothelial growth factor-ɑ, fibroblast growth factor, NHS, EDC and Ag / Cu deposited UiO-66-OH@ modified material in step S4 is 0.2-0.4:0.1-0.3:0.5-1:0.5-1:8-10.

5. The external-use composition for promoting surgical wound healing according to claim 1, characterized in that The preparation method of the chlorogenic acid / oleanolic acid loaded chitosan is as follows: T1. Dissolving chitosan in acid to obtain a chitosan solution; T2. Add chlorogenic acid and oleanolic acid to water, add NHS and EDC, stir and activate, add chitosan solution, stir and react, dialyze, and dry to prepare chlorogenic acid / oleanolic acid-loaded chitosan.

6. The external-use composition for promoting surgical wound healing according to claim 5, characterized in that The concentration of the chitosan solution in step T1 is 2-3wt%, and the acid solution is a 1-2wt% acetic acid or lactic acid solution; the mass ratio of chlorogenic acid, oleanolic acid, NHS, EDC and chitosan solution in step T2 is 0.5-1:0.5-1:0.3-0.5:0.3-0.5:150-200.

7. The external-use composition for promoting surgical wound healing according to claim 1, characterized in that The concentration of the hydrogen peroxide in step U1 is 28-32wt%, the concentration of the alkali solution is 8-12wt%, and the alkali is NaOH or KOH; the brine in step U2 is a NaCl solution with a concentration of 3-5wt%, and the number of repeated freeze-thaw treatments is 3-5 times; the mass ratio of the preliminary decellularized material, ficin, and lysozyme in step U3 is 10:1-2:1-2, the enzymatic hydrolysis temperature is 36-40°C, and the time is 8-10 hours.

8. A method for preparing the external-use composition for promoting surgical wound healing according to claim 1, characterized in that: The following steps are involved: (1) Banyan bark powder, Chinese medicine powder, decellularized material, collagen peptide, and modified nano-hydroxyapatite are mixed uniformly in proportion to prepare component A; (2) Mix the carboxylated ionic liquid, chlorogenic acid / oleanolic acid loaded chitosan, platelet-rich plasma and water in proportion to obtain component B, and store it at 2-6°C.

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