Pharmaceutical composition for promoting skin microcirculation and accelerating wound healing and application thereof

Abstract

The invention discloses a pharmaceutical composition for promoting skin microcirculation and accelerating wound healing and application of the pharmaceutical composition, belongs to the technical field of skin healing drugs, and aims to solve the technical problem that in the prior art, the permeation effect of active ingredients in an external pharmaceutical composition on skin and the effect of promoting wound healing and repairing need to be further improved. The pharmaceutical composition for promoting skin microcirculation and accelerating wound healing comprises the following components in parts by weight: 25 parts of an active component, 2-5 parts of a gel matrix, 1-2 parts of a penetration enhancer, 1-2 parts of a thickening agent, 3-5 parts of an emulsifier and 4-6 parts of an auxiliary additive. A flavonoid compound and a triterpenoid saponin compound are subjected to scientific compatibility, a homogeneous dispersion method of active ingredients is optimized, and chitosan and catechol modified carbomer is used as a gel matrix, so that the active ingredients of the medicine are easier to permeate into skin, microcirculation is remarkably improved, inflammation and bacteria are resisted, and the curative effect is good. The wound repairing effect is accelerated.

Description

Technical Field

[0001] The present invention relates to the technical field of skin healing drugs, and in particular to a drug composition for promoting skin microcirculation and accelerating wound healing and an application thereof. Background Art

[0002] With the advancement of modern medicine, significant progress has been made in the treatment of skin injuries. However, existing treatments still suffer from issues such as slow efficacy, insufficient local tissue oxygen supply, and persistent inflammatory responses, resulting in a complex and lengthy repair process for skin injuries. In particular, existing pharmaceutical compositions have yet to achieve the desired effects in promoting microcirculation, combating inflammation, combating bacteria, and accelerating wound healing in the treatment of skin injuries such as trauma, ulcers, and burns.

[0003] Flavonoids and triterpenoid saponins, as important active ingredients in natural plant extracts, possess multiple biological activities, including antioxidant, anti-inflammatory, and antibacterial properties. They have been widely used in drug development in recent years. Flavonoids, such as extracts from Scutellaria baicalensis and Salvia officinalis, have shown significant potential in improving microcirculation and providing anti-inflammatory and antibacterial properties. Triterpenoid saponins, such as extracts from Panax ginseng, Licorice, and Centella asiatica, have demonstrated promising wound healing properties by enhancing local immune responses and promoting cell repair and regeneration.

[0004] However, a single plant extract can usually only play a partial role and is difficult to fully promote the repair of skin damage. Existing topical drug dosage forms are mostly creams or emulsions, and plant extracts contain a large amount of hydrophobic active substances. When plant extracts are used as the active ingredients of the drug, it is difficult to achieve a uniform dispersion effect during preparation and molding, resulting in poor permeability and low absorption rate, making it difficult to achieve the expected therapeutic effect. In addition, traditional creams or emulsions often use carbomer as a gelling agent, but they still have significant deficiencies in microcirculation activation and multi-stage healing regulation, resulting in the need to further improve the penetration of the active ingredients of the drug into the skin and the effect of promoting wound healing and repair.

[0005] In view of the technical defects in this aspect, a solution is now proposed. Summary of the Invention

[0006] The purpose of the present invention is to provide a pharmaceutical composition for promoting skin microcirculation and accelerating wound healing and its application, so as to solve the technical problem in the prior art that the active ingredients in external-use pharmaceutical compositions need to be further improved in terms of penetration into the skin and the effect of promoting wound healing and repair.

[0007] The purpose of the present invention can be achieved through the following technical solutions:

[0008] A pharmaceutical composition for promoting skin microcirculation and accelerating wound healing, comprising the following components in parts by weight: 25 parts of an active ingredient, 2-5 parts of a gel matrix, 1-2 parts of a penetration enhancer, 1-2 parts of a thickener, 3-5 parts of an emulsifier, and 4-6 parts of an auxiliary additive;

[0009] The active ingredient is composed of flavonoids and triterpenoid saponins in a weight ratio of 15-80:20-110;

[0010] The penetration enhancer consists of soybean phosphate and epoxidized soybean oil in a weight ratio of 2:1.

[0011] Furthermore, the flavonoid compound comprises 10-50 parts of Scutellaria baicalensis extract and 5-30 parts of Sage extract by weight.

[0012] Furthermore, the triterpenoid saponin compounds include 10-50 parts of ginseng extract, 5-30 parts of licorice extract, and 5-30 parts of Centella asiatica extract in parts by weight.

[0013] Furthermore, the preparation method of the gel matrix is as follows: 3,4-dihydroxyphenylacetic acid, carbomer, and deionized water are mixed, the pH of the system is adjusted to 5-6, and the system is stirred until the system is dissolved. 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and N-hydroxycarbodiimide are added to the reaction system, and the reaction is stirred at room temperature for 2-3 hours. The chitosan solution is added to the reaction system, and the reaction is carried out at room temperature for 20-24 hours. Post-treatment is performed to obtain a gel matrix.

[0014] The synthetic reaction mechanism of the gel matrix is:

[0015] During the reaction, carbomer swells in water. By adjusting the pH, some carboxyl groups on 3,4-dihydroxyphenylacetic acid and carbomer are deprotonated to form a viscous gel. 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride reacts with the carboxyl groups to generate an unstable O-acylisourea intermediate. N-hydroxysuccinimide then replaces the intermediate to generate a more stable N-hydroxysuccinimide ester. The amino groups of chitosan attack carbomer or the N-hydroxysuccinimide activated ester of 3,4-dihydroxyphenylacetic acid to form an amide bond, achieving covalent cross-linking between polymers. Chitosan and o-diphenol are then modified on the carbomer to prepare a gel matrix.

[0016] Furthermore, the amount ratio of the 3,4-dihydroxyphenylacetic acid, carbomer, deionized water, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and N-hydroxycarbodiimide to the chitosan solution is 1g:2g:20mL:3g:1.8g:15mL, the chitosan solution is composed of chitosan and 1wt% glacial acetic acid aqueous solution at 1g:30mL, and the deacetylation degree of the chitosan is 80-85%. The post-treatment includes: after the reaction is completed, placing the reaction solution in a 3000Da dialysis bag, dialyzing it in a deionized water environment for 3 days, changing the water every 6 hours, and then placing the substance in the dialysis bag in a freeze dryer at a temperature of -30°C, freeze-drying to constant weight to obtain a gel matrix.

[0017] Furthermore, the thickener is xanthan gum, the emulsifier is composed of Tween 20 and sodium lauryl sulfate in a weight ratio of 3:2, and the auxiliary additive is composed of a moisturizer lauryl alcohol and a stabilizer sodium ascorbate in a weight ratio of 1-2:5-6.

[0018] Furthermore, the preparation method of the pharmaceutical composition for promoting skin microcirculation and accelerating wound healing comprises the following steps:

[0019] S1. Mix the emulsifier, auxiliary additives and solvent, stir for 30-50 minutes, add the active ingredient to the reaction system, stir evenly, and shear at high speed to obtain a suspension. The suspension is transferred to a high-pressure homogenizer and homogenized to obtain an active ingredient dispersion;

[0020] S2. Mixing and stirring the gel matrix, permeation enhancer, and active ingredient dispersion, swelling at room temperature for 40-60 minutes, adjusting the system pH to 6.5, and post-treating to obtain a mixed gel solution;

[0021] S3. Add a thickener to the mixed gel solution, stir and mix for 20-30 minutes to obtain a finished drug product.

[0022] Furthermore, in step S1, the solvent is composed of ethanol and deionized water in a volume ratio of 2:1, the amount ratio of the solvent to the active ingredient is 5 mL:1 g, the high-speed shear speed is 12000-13000 r / min, the high-speed shear time is 5-6 min, the pressure of the high-pressure homogenizer is 500-700 bar, the temperature is 20-25 ° C, and the homogenization time is 15-25 min. In step S2, the post-processing operation includes: after the reaction is completed, transferring the reaction solution to a rotary evaporator at a temperature of 45-55 ° C, and removing low-boiling substances under reduced pressure to obtain a mixed gel solution.

[0023] The invention discloses an application of a pharmaceutical composition for promoting skin microcirculation and accelerating wound healing. The pharmaceutical composition for promoting skin microcirculation and accelerating wound healing is applied to the repair of skin injuries, wherein the skin injuries include: open injuries, ulcerative injuries, burns, and frostbite.

[0024] The present invention has the following beneficial effects:

[0025] 1. The pharmaceutical composition of the present invention for promoting skin microcirculation and accelerating wound healing uses natural herbal extracts as the core to reduce the risk of side effects and meet the needs of modern medical care and health care. Flavonoids and triterpenoid saponins are scientifically combined. Flavonoids such as extracts of Scutellaria baicalensis and Salvia officinalis are used to improve the microcirculation and anti-inflammatory and antibacterial properties of wounds. Triterpenoid saponins such as extracts of ginseng, licorice, and Centella asiatica are used to enhance local immune responses, promote cell repair and regeneration, and improve wound healing effects. The composition is then homogeneously dispersed, and through the action of emulsifiers and high-pressure homogenization, the active ingredients are forced to form smaller particles and become more stable.

[0026] 2. The pharmaceutical composition for promoting skin microcirculation and accelerating wound healing of the present invention adds an emulsifier during the homogeneous dispersion process to reduce interfacial tension, thereby promoting the homogeneous dispersion of hydrophobic compounds in the active ingredients, such as flavonoids and saponins, and improving the solubility of the hydrophobic components in the active ingredients to form mixed micelles with the gel matrix, thereby improving the drug encapsulation rate and avoiding aggregation and inactivation of the active ingredients. The emulsifier can also improve the subsequent homogenization and high-pressure treatment effects, making the homogenized particle size smaller and more uniform, thereby improving its transdermal absorption effect. Penetration enhancers such as soybean phosphate and epoxidized soybean oil can enhance drug absorption, making the active ingredients of the drug easier to penetrate the skin, thereby significantly improving microcirculation, anti-inflammatory and antibacterial, and accelerating wound repair.

[0027] 3. The pharmaceutical composition for promoting skin microcirculation and accelerating wound healing of the present invention is prepared by reacting 3,4-dihydroxyphenylacetic acid, carbomer, and chitosan, and modifying chitosan and o-diphenol on the carbomer to obtain a gel matrix. Chitosan undergoes an amidation reaction with the carboxyl groups on 3,4-dihydroxyphenylacetic acid or carbomer to form a three-dimensional cross-linked network, which can delay the release rate of the active ingredient and ensure the continuity of wound repair. The o-diphenol structure in the gel matrix binds to the chitosan amino group through hydrogen bonds, enhancing the adhesion of the gel. At the same time, its antioxidant activity cooperates with the active ingredient to enhance the anti-inflammatory effect of the drug on the wound, reduce oxidative stress damage to the wound, promote wound repair and regeneration, and increase the healing rate of the wound. DETAILED DESCRIPTION

[0028] The technical solutions of the present invention will be clearly and completely described below in conjunction with the embodiments. 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 creative efforts are within the scope of protection of the present invention.

[0029] In the present invention, the carbomer is carbomer 940, which is selected from Xi'an Tianzheng Pharmaceutical Excipients Co., Ltd. and is a pharmaceutical excipient with an active ingredient content of 99%;

[0030] In the present invention, chitosan is selected from Ruichengkang Pharmaceutical Technology (Shaanxi) Co., Ltd., which is a pharmaceutical excipient with a CAS number of 9012-76-4, an active ingredient content of 99%, and a deacetylation degree of 80-85%;

[0031] In this application, the CAS number of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride is 247-361-2;

[0032] In this application, the CAS number of N-hydroxybenzoic acid imide is 6066-82-6;

[0033] In the present application, the CAS number of 3,4-dihydroxyphenylacetic acid is 102-32-9.

[0034] Example 1

[0035] This embodiment provides a method for preparing a gel matrix for a pharmaceutical composition for promoting skin microcirculation and accelerating wound healing, comprising the following steps:

[0036] Chitosan and 1 wt% glacial acetic acid aqueous solution were mixed at a ratio of 1 g:30 mL and stirred until the system was dissolved to obtain a chitosan solution for later use;

[0037] Weigh: 10 g of 3,4-dihydroxyphenylacetic acid, 20 g of carbomer 940, and 200 mL of deionized water are added to a flask and mixed. Triethanolamine is added to the flask to adjust the pH of the system to 5, and the system is stirred until it is dissolved. 30 g of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and 18 g of N-hydroxybenzamide are added to the flask, and the mixture is stirred and reacted at room temperature for 2 h. 150 mL of chitosan solution is added to the flask, and the mixture is reacted at room temperature for 20 h. The reaction solution is placed in a dialysis bag with a cutoff of 3000 Da and dialyzed in a deionized water environment for 3 days. The water is changed every 6 h, and the substance in the dialysis bag is placed in a freeze dryer at -30 ° C and freeze-dried to constant weight to obtain a gel matrix.

[0038] Example 2

[0039] This embodiment provides a method for preparing a gel matrix for a pharmaceutical composition for promoting skin microcirculation and accelerating wound healing, comprising the following steps:

[0040] Chitosan and 1 wt% glacial acetic acid aqueous solution were mixed at a ratio of 1 g:30 mL and stirred until the system was dissolved to obtain a chitosan solution for later use;

[0041] Weigh: 10 g of 3,4-dihydroxyphenylacetic acid, 20 g of carbomer 940, and 200 mL of deionized water were added to a flask and mixed. Triethanolamine was added to the flask to adjust the pH of the system to 5.5, and stirred until the system dissolved. 30 g of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and 18 g of N-hydroxybenzamide were added to the flask, and the mixture was stirred and reacted at room temperature for 2.5 h. 150 mL of chitosan solution was added to the flask and the mixture was reacted at room temperature for 22 h. The reaction solution was placed in a dialysis bag with a cutoff of 3000 Da and dialyzed in deionized water for 3 days, with the water changed every 6 h. The substance in the dialysis bag was then placed in a freeze dryer at -30 ° C and freeze-dried to constant weight to obtain a gel matrix.

[0042] Example 3

[0043] This embodiment provides a method for preparing a gel matrix for a pharmaceutical composition for promoting skin microcirculation and accelerating wound healing, comprising the following steps:

[0044] Chitosan and 1 wt% glacial acetic acid aqueous solution were mixed at a ratio of 1 g:30 mL and stirred until the system was dissolved to obtain a chitosan solution for later use;

[0045] Weigh: 10 g of 3,4-dihydroxyphenylacetic acid, 20 g of carbomer 940, and 200 mL of deionized water are added to a flask and mixed. Triethanolamine is added to the flask to adjust the pH of the system to 6, and the system is stirred until it is dissolved. 30 g of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and 18 g of N-hydroxycarbodiimide are added to the flask, and the mixture is stirred and reacted at room temperature for 3 h. 150 mL of chitosan solution is added to the flask, and the mixture is reacted at room temperature for 24 h. The reaction solution is placed in a dialysis bag with a cutoff of 3000 Da and dialyzed in a deionized water environment for 3 days. The water is changed every 6 h. The substance in the dialysis bag is then placed in a freeze dryer at -30 ° C and freeze-dried to constant weight to obtain a gel matrix.

[0046] Example 4

[0047] This embodiment provides a method for preparing a pharmaceutical composition for promoting skin microcirculation and accelerating wound healing, comprising the following steps:

[0048] Step I: Prepare active ingredients

[0049] Weigh 10 g of Scutellaria baicalensis extract, 5 g of Sage extract, 10 g of Ginseng extract, 5 g of Licorice extract, and 5 g of Centella asiatica extract and mix well to obtain the active ingredient;

[0050] Step II: Homogeneous dispersion

[0051] Tween 20 and sodium lauryl sulfate were mixed uniformly in a weight ratio of 3:2 to obtain an emulsifier;

[0052] The moisturizing agent lauryl alcohol and the stabilizer sodium ascorbate are mixed uniformly in a weight ratio of 1:5 to obtain an auxiliary additive;

[0053] Ethanol and deionized water were mixed uniformly in a volume ratio of 2:1 to obtain a solvent;

[0054] Weigh 300 g of emulsifier, 400 g of auxiliary additives, and 12,500 mL of solvent into a flask, mix, and stir for 30 minutes. Add 2,500 g of the active ingredient prepared in step I to the flask and stir for 20 minutes. Transfer the solution in the flask to a high-speed shearing machine, set the high-speed shear speed to 12,000 rpm, and high-speed shear for 5 minutes to obtain a suspension.

[0055] The suspension was transferred to a high-pressure homogenizer, and the pressure and temperature of the high-pressure homogenizer were set to 500 bar, 20° C., and 15 min, and the mixture was discharged to obtain an active ingredient dispersion.

[0056] Step III: Preparation of finished drug product

[0057] Soybean phosphate and epoxidized soybean oil are mixed uniformly in a weight ratio of 2:1 to obtain a penetration enhancer;

[0058] Weigh 200 g of the gel matrix prepared in Example 1 and 100 g of a permeation enhancer and add them to the active ingredient dispersion prepared in Step II. Mix and stir, and allow to swell at room temperature for 40 min. Adjust the pH of the system to 6.5 with 0.1 mol / L sodium hydroxide solution. Transfer the reaction solution to a rotary evaporator at 45°C, and remove low-boiling substances under reduced pressure to obtain a mixed gel solution.

[0059] 100 g of xanthan gum, a thickener, was added to the mixed gel solution, and the mixture was stirred for 20 minutes to obtain a finished drug product.

[0060] Example 5

[0061] This embodiment provides a method for preparing a pharmaceutical composition for promoting skin microcirculation and accelerating wound healing, comprising the following steps:

[0062] Step I: Prepare active ingredients

[0063] Weigh 30 g of Scutellaria baicalensis extract, 17.5 g of Sage extract, 30 g of Ginseng extract, 17.5 g of Licorice extract, and 17.5 g of Centella asiatica extract and mix well to obtain the active ingredient;

[0064] Step II: Homogeneous dispersion

[0065] Tween 20 and sodium lauryl sulfate were mixed uniformly in a weight ratio of 3:2 to obtain an emulsifier;

[0066] The moisturizing agent lauryl alcohol and the stabilizer sodium ascorbate are mixed uniformly in a weight ratio of 1.5:5.5 to obtain an auxiliary additive;

[0067] Ethanol and deionized water were mixed uniformly in a volume ratio of 2:1 to obtain a solvent;

[0068] Weigh 400 g of emulsifier, 500 g of auxiliary additives, and 12,500 mL of solvent into a flask, mix, and stir for 40 min. Add 2,500 g of the active ingredient prepared in step I to the flask and stir for 25 min. Transfer the solution in the flask to a high-speed shearing machine, set the high-speed shear speed to 12,500 r / min, and high-speed shear for 5.5 min to obtain a suspension.

[0069] The suspension was transferred to a high-pressure homogenizer, and the pressure and temperature of the high-pressure homogenizer were set to 600 bar, 23° C., and 20 min, and the mixture was discharged to obtain an active ingredient dispersion.

[0070] Step III: Preparation of finished drug product

[0071] Soybean phosphate and epoxidized soybean oil are mixed uniformly in a weight ratio of 2:1 to obtain a penetration enhancer;

[0072] Weigh 350 g of the gel matrix prepared in Example 2 and 150 g of a permeation enhancer and add them to the active ingredient dispersion prepared in Step II. Mix and stir, and allow to swell at room temperature for 50 min. Adjust the pH of the system to 6.5 with 0.1 mol / L sodium hydroxide solution. Transfer the reaction solution to a rotary evaporator at 50°C, and remove low-boiling substances under reduced pressure to obtain a mixed gel solution.

[0073] 150 g of xanthan gum, a thickener, was added to the mixed gel solution, and the mixture was stirred for 25 minutes to obtain a finished drug product.

[0074] Example 6

[0075] This embodiment provides a method for preparing a pharmaceutical composition for promoting skin microcirculation and accelerating wound healing, comprising the following steps:

[0076] Step I: Prepare active ingredients

[0077] Weigh 50 g of Scutellaria baicalensis extract, 30 g of Sage extract, 50 g of Ginseng extract, 30 g of Licorice extract, and 30 g of Centella asiatica extract and mix well to obtain the active ingredient;

[0078] Step II: Homogeneous dispersion

[0079] Tween 20 and sodium lauryl sulfate were mixed uniformly in a weight ratio of 3:2 to obtain an emulsifier;

[0080] The moisturizing agent lauryl alcohol and the stabilizer sodium ascorbate are mixed uniformly in a weight ratio of 2:6 to obtain an auxiliary additive;

[0081] Ethanol and deionized water were mixed uniformly in a volume ratio of 2:1 to obtain a solvent;

[0082] Weigh 500 g of emulsifier, 600 g of auxiliary additives, and 12,500 mL of solvent into a flask, mix, and stir for 50 min. Add 2,500 g of the active ingredient prepared in step I to the flask and stir for 30 min. Transfer the solution in the flask to a high-speed shearing machine, set the high-speed shear speed to 13,000 rpm, and high-speed shear for 6 min to obtain a suspension.

[0083] The suspension was transferred to a high-pressure homogenizer, and the pressure and temperature of the high-pressure homogenizer were set to 700 bar, 25° C., and 25 min, and the mixture was discharged to obtain an active ingredient dispersion.

[0084] Step III: Preparation of finished drug product

[0085] Soybean phosphate and epoxidized soybean oil are mixed uniformly in a weight ratio of 2:1 to obtain a penetration enhancer;

[0086] Weigh 505 g of the gel matrix prepared in Example 3 and 200 g of a permeation enhancer and add them to the active ingredient dispersion prepared in Step II. Mix and stir, and allow to swell at room temperature for 60 min. Adjust the pH of the system to 6.5 with 0.1 mol / L sodium hydroxide solution. Transfer the reaction solution to a rotary evaporator at 55°C, and remove low-boiling substances under reduced pressure to obtain a mixed gel solution.

[0087] 20 g of xanthan gum, a thickener, was added to the mixed gel solution, and the mixture was stirred for 30 minutes to obtain a finished drug product.

[0088] Comparative Example 1

[0089] The difference between this comparative example and Example 6 is that no 3,4-dihydroxyphenylacetic acid was added during the preparation of the gel matrix used.

[0090] Comparative Example 2

[0091] The difference between this comparative example and Example 6 is that the gel matrix used is Carbomer 940.

[0092] Comparative Example 3

[0093] The difference between this comparative example and Example 6 is that no emulsifier is added in step II.

[0094] Comparative Example 4

[0095] The difference between this comparative example and Example 6 is that in step III, the penetration enhancer is soybean phosphate.

[0096] Performance testing:

[0097] 63 SPF female mice were randomly divided into 7 groups, with 9 mice in each group. The rats were anesthetized by intraperitoneal injection of 4% chloral hydrate, and the hair on the back of the rats was shaved to create a circular wound with a diameter of 8 mm. The finished drug samples prepared in Examples 4-6 and Comparative Examples 1-4 were applied to the wound surface, respectively. The wound healing was observed on the 3rd, 5th, and 7th days after surgery. The wound tissue was taken and the wound area was observed histologically by hematoxylin-eosin (H&E) staining. Then, the formula Determination of wound healing rate, S X X is 3, 5, and 7, respectively, meaning the wound surface area on the 3rd, 5th, and 7th days after surgery. S0 is the wound surface area after surgery. Wound tissues were collected on the 3rd, 5th, and 7th days for immune component analysis, and the expression levels of TNF-α, IL-1β, IL-6, TGF-β1, PDGFD, and CD31 in the tissues surrounding the wound were detected.

[0098] The specific test results are shown in Table 1-2 below.

[0099] Table 1-Wound healing test data

[0100]

[0101]

[0102] Table 2 - Wound tissue immune component analysis data

[0103]

[0104] Data Analysis:

[0105] Comparative analysis of the data in Tables 1-2 above shows that the wound healing rate of the finished drug prepared by the present invention reached 47.2% on the third day. In the immune component analysis, the expression of TNF-α was reduced to 34.2%, the expression of IL-1β was reduced to 28.2%, the expression of IL-6 was reduced to 25.2%, the expression of TGF-β1 was reduced to 30.8%, the expression of PDGFD was increased to 36.2%, and the expression of CD31 was increased by 21.9%. On the 5th day, the wound healing rate reached 66.1%. In the immune component analysis, the expression of TNF-α was reduced to 25.1%, the expression of IL-1β was reduced to 21.1%, the expression of IL-6 was reduced to 22.8%, the expression of TGF-β1 was reduced to 26.1%, and the expression of PDGFD was increased to 44.9%. , the expression level of CD31 increased by 35.5%. On the 7th day, the wound healing rate reached 95.7%. In the immune component analysis, the expression level of TNF-α decreased to 19.1%, the expression level of IL-1β decreased to 15.2%, the expression level of IL-6 decreased to 15.1%, the expression level of TGF-β1 decreased to 20.8%, the expression level of PDGFD increased to 48.8%, and the expression level of CD31 increased by 42.6%. The performance test data of each item are better than those of the control example, indicating that the present invention optimizes the homogeneous dispersion method of the active ingredients through scientific combination of flavonoids and triterpenoid saponins, and uses chitosan and o-diphenol modified carbomer as the gel matrix, which not only makes the active ingredients of the drug easier to penetrate the skin, but also significantly improves microcirculation, anti-inflammatory and antibacterial effects, and accelerates the wound repair effect.

[0106] The above contents are merely examples and explanations of the structure of the present invention. Those skilled in the art may make various modifications or additions to the described specific embodiments or replace them in a similar manner. As long as they do not deviate from the structure of the invention or exceed the scope defined by the claims, they shall fall within the scope of protection of the present invention.

[0107] Throughout this specification, references to terms such as "one embodiment," "example," or "specific example" indicate that the specific features, structures, materials, or characteristics described in conjunction with that embodiment or example are included in at least one embodiment or example of the present invention. In this specification, schematic representations of these terms do not necessarily refer to the same embodiment or example. Furthermore, the specific features, structures, materials, or characteristics described may be combined in any suitable manner in any one or more embodiments or examples.

[0108] The preferred embodiments of the present invention disclosed above are intended only to help illustrate the present invention. These preferred embodiments do not exhaustively describe all details, nor do they limit the present invention to specific embodiments. Obviously, many modifications and variations are possible based on the contents of this specification. These embodiments are selected and described in detail in this specification to better explain the principles and practical applications of the present invention, thereby enabling those skilled in the art to better understand and utilize the present invention. The present invention is limited only by the claims and their full scope and equivalents.

Claims

1. A pharmaceutical composition for promoting skin microcirculation and accelerating wound healing, characterized in that: The invention comprises the following components in parts by weight: 25 parts of active ingredient, 2-5 parts of gel matrix, 1-2 parts of penetration enhancer, 1-2 parts of thickener, 3-5 parts of emulsifier and 4-6 parts of auxiliary additives; The active ingredient is obtained by any combination of flavonoid compounds and triterpenoid saponin compounds; The penetration enhancer consists of soybean phosphate and epoxidized soybean oil in a weight ratio of 2:

1.

2. A pharmaceutical composition for promoting skin microcirculation and accelerating wound healing according to claim 1, characterized in that: The flavonoid compound comprises 10-50 parts of scutellaria baicalensis extract and 5-30 parts of sage extract by weight.

3. A pharmaceutical composition for promoting skin microcirculation and accelerating wound healing according to claim 1, characterized in that: The triterpenoid saponin compound comprises, by weight, 10-50 parts of ginseng extract, 5-30 parts of licorice extract, and 5-30 parts of Centella asiatica extract.

4. The pharmaceutical composition for promoting skin microcirculation and accelerating wound healing according to claim 1, characterized in that: The preparation method of the gel matrix is as follows: 3,4-dihydroxyphenylacetic acid, carbomer, and deionized water are mixed, the pH of the system is adjusted to 5-6, and the system is stirred until the system is dissolved. 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and N-hydroxycarbodiimide are added to the reaction system, and the reaction is stirred at room temperature for 2-3 hours. The chitosan solution is added to the reaction system, and the reaction is carried out at room temperature for 20-24 hours. After post-treatment, the gel matrix is obtained.

5. The pharmaceutical composition for promoting skin microcirculation and accelerating wound healing according to claim 3, characterized in that: The amount ratio of the 3,4-dihydroxyphenylacetic acid, carbomer, deionized water, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and N-hydroxycarbodiimide to the chitosan solution is 1g:2g:20mL:3g:1.8g:15mL. The chitosan solution is composed of chitosan and 1wt% glacial acetic acid aqueous solution at a ratio of 1g:30mL. The deacetylation degree of the chitosan is 80-85%. The post-treatment includes: after the reaction is completed, placing the reaction solution in a 3000Da dialysis bag, dialyzing it in a deionized water environment for 3 days, changing the water every 6 hours, and then placing the material in the dialysis bag in a freeze dryer at a temperature of -30°C and freeze-drying it to constant weight to obtain a gel matrix.

6. The pharmaceutical composition for promoting skin microcirculation and accelerating wound healing according to claim 1, characterized in that: The thickener is xanthan gum, the emulsifier is composed of Tween 20 and sodium lauryl sulfate in a weight ratio of 3:2, and the auxiliary additive is composed of a moisturizer lauryl alcohol and a stabilizer sodium ascorbate in a weight ratio of 1-2:5-6.

7. The pharmaceutical composition for promoting skin microcirculation and accelerating wound healing according to claim 1, characterized in that: The preparation method of the pharmaceutical composition for promoting skin microcirculation and accelerating wound healing comprises the following steps: S1. Mix the emulsifier, auxiliary additives and solvent, stir for 30-50 minutes, add the active ingredient to the reaction system, stir evenly, and shear at high speed to obtain a suspension. The suspension is transferred to a high-pressure homogenizer and homogenized to obtain an active ingredient dispersion; S2. Mixing and stirring the gel matrix, permeation enhancer, and active ingredient dispersion, swelling at room temperature for 40-60 minutes, adjusting the system pH to 6.5, and post-treating to obtain a mixed gel solution; S3. Add a thickener to the mixed gel solution, stir and mix for 20-30 minutes to obtain a finished drug product.

8. The pharmaceutical composition for promoting skin microcirculation and accelerating wound healing according to claim 1, characterized in that: In step S1, the solvent is composed of ethanol and deionized water in a volume ratio of 2:1, the amount ratio of the solvent to the active ingredient is 5 mL:1 g, the high-speed shear speed is 12000-13000 r / min, the high-speed shear time is 5-6 min, the pressure of the high-pressure homogenizer is 500-700 bar, the temperature is 20-25 ° C, and the homogenization time is 15-25 min.

9. Use of a pharmaceutical composition for promoting skin microcirculation and accelerating wound healing, characterized in that: The pharmaceutical composition for promoting skin microcirculation and accelerating wound healing as claimed in any one of claims 1 to 8 is applied to the repair of skin injuries, wherein the skin injuries include open injuries, ulcerative injuries, burns and frostbite.

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