Medicine for promoting healing of skin injury and its preparation method

Abstract

This invention relates to a drug for promoting skin damage repair and healing, and its preparation method, belonging to the field of biomedical technology. The drug includes Astragalus membranaceus extract, liposome-encapsulated Panax notoginseng total saponins-RGD peptide, Lonicera japonica-Maca extract, Centella asiatica-hydroxypropyl-β-cyclodextrin inclusion complex, and dipotassium glycyrrhizate. The Astragalus membranaceus extract is obtained by soaking Astragalus membranaceus in honey, baking, extracting with deionized water, and purifying by adsorption on a Sephadex G-15 column. The Lonicera japonica-Maca extract is obtained by mixing dried Lonicera japonica powder and dried Maca root powder in a mass ratio of (3-5):(1-1.7), enzymatically hydrolyzing with cellulase, then co-enzymatically hydrolyzing with fig protease and papain, and purifying by adsorption on an HPD722 macroporous adsorption resin column. The components are formulated in specific proportions to reduce the risk of allergies and skin irritation, rationally promote skin damage healing, and effectively inhibit melanin deposition.

Description

Technical Field

[0001] This invention belongs to the field of biomedical technology, specifically relating to a drug that promotes the repair and healing of skin damage and its preparation method. Background Technology

[0002] Traditional Chinese medicine (TCM) topical ointments have a long history of application in skin injury repair. Based on the TCM theory of "promoting blood circulation, removing blood stasis, and promoting tissue regeneration and wound healing," they regulate the wound microenvironment through the synergistic effect of compound ingredients, demonstrating unique advantages in scenarios such as trauma, ulcers, and burns. However, with the advancement of medical technology, the previously crude TCM ointments still have shortcomings in terms of safety, efficacy, and control of melanin deposition, as detailed below.

[0003] Allergic reactions are frequent and complex: Traditional Chinese medicine external application formulas contain a wide variety of allergens, including plant proteins, volatile oils, and alkaloids. Among these, the resinous components in frankincense and myrrh, and the terpenoids in rosin are common allergens. The incidence of local allergic reactions to traditional ointments containing these ingredients can reach 10%-20%, manifesting as erythema, papules, vesicles, and even contact dermatitis, with an even higher incidence in people with allergic constitutions. More importantly, some compound formulas, due to improper processing of medicinal materials (such as incomplete detoxification of aconite), may cause acute irritation reactions such as local burning pain and swelling, requiring discontinuation of treatment in severe cases.

[0004] The safety of drug combinations lacks scientific validation: Traditional compound prescriptions often follow the "principal, assistant, adjuvant, and guide" theory, but modern research has confirmed that some classic combinations pose potential risks. For example, while the combination of Angelica sinensis and Salvia miltiorrhiza can enhance blood-activating effects, both contain coumarin compounds, which may competitively inhibit liver metabolic enzymes, leading to abnormally high local drug concentrations. Similarly, while the combination of Lonicera japonica and Scutellaria baicalensis can strengthen anti-inflammatory effects, their tannins may combine to form insoluble complexes, reducing efficacy and increasing the risk of skin irritation. Currently, the safety thresholds for drug combinations in most compound prescriptions still lack systematic research.

[0005] Slow onset of action and low response rate in complex wounds: Traditional Chinese medicine (TCM) topical applications rely on the synergistic regulation of multiple components, but their repair efficiency for complex wounds such as ischemic and infected wounds is significantly lower than that of Western medicine. The wound shrinkage rate of using TCM ointments alone is slower than that of combined treatment with recombinant human vascular endothelial growth factor (rhVEGF). This is because the bioavailability of the effective components of TCM (such as astragalus polysaccharides and tanshinone) is low, making it impossible to quickly initiate key repair processes such as angiogenesis and epithelial cell migration.

[0006] Poor control of melanin deposition: Some traditional Chinese medicines (such as Psoralea corylifolia, Angelica dahurica, and Angelica pubescens) contain furanocoumarins, which can bind to tyrosinase in melanocytes, enhancing their sensitivity to ultraviolet light and leading to hypersynthetic melanin production in the local area. The blood-activating components of some herbs (such as Ligusticum chuanxiong and Carthamus tinctorius) may prolong the local inflammatory window, prompting macrophages to release melanin-producing factors (such as stem cell factor SCF). Wounds are prone to pigmentation. Current research on topical Chinese medicines focuses primarily on promoting healing, with insufficient attention paid to the regulation of melanin metabolism. Although some studies have found that asiaticoside and baicalin have certain melanin-inhibiting effects, their effects are often negated in compound preparations due to improper compatibility (such as use with Psoralea corylifolia), making it difficult to achieve a synergistic effect of "promoting healing and inhibiting pigmentation."

[0007] Therefore, topical medications still need to be improved in terms of safety, bioavailability, and prevention of pigment deposition. The extraction and formulation of ingredients should be optimized to achieve the triple goal of "safety, efficient healing, and low pigment deposition" and better meet the needs of repair quality. Summary of the Invention

[0008] To address the shortcomings of existing topical Chinese medicine (TCM) remedies for skin damage repair, particularly in terms of safety, efficacy, and control of pigmentation, this invention provides a drug for promoting skin damage repair and healing, along with its preparation method. A special method is used to prepare Astragalus membranaceus extract, liposome-encapsulated Panax notoginseng total saponins-RGD peptide, and Lonicera japonica-Maca extract. These are then combined with a Centella asiatica-hydroxypropyl-β-cyclodextrin inclusion complex and dipotassium glycyrrhizate in a specific ratio. This comprehensively solves the problems of safety, therapeutic efficacy, and control of skin pigmentation associated with traditional TCM topical remedies. By removing impurities that cause allergies, the invention achieves a comprehensive effect of reducing the risk of allergies and skin irritation, effectively promoting skin damage healing, and effectively inhibiting melanin deposition, thus effectively improving the efficacy of "safety, efficient healing, and low pigmentation." The specific technical solution is as follows:

[0009] A drug for promoting skin damage repair and healing, comprising the following raw materials in parts by weight: 25-30 parts of roasted Astragalus membranaceus extract, 11-15 parts of liposome-encapsulated Panax notoginseng total saponins-RGD peptide, 12-15 parts of honeysuckle-maca extract, 6-10 parts of asiaticoside-hydroxypropyl-β-cyclodextrin inclusion complex, and 3-5 parts of dipotassium glycyrrhizate; the roasted Astragalus membranaceus extract is prepared by soaking Astragalus membranaceus in honey, baking, extracting with deionized water, and then processing with Sephadex. Astragalus membranaceus extract obtained by adsorption and purification using G-15 column; ginseng total saponins-RGD peptide encapsulated in liposomes with a mass ratio of (8-10):(3-5) for total saponins to RGD peptide; honeysuckle-mac extract obtained by mixing honeysuckle powder and maca root powder in a mass ratio of (3-5):(1-1.7), followed by enzymatic hydrolysis with cellulase, then by co-enzymatic hydrolysis with fig protease and papain, and finally by adsorption and purification using HPD722 macroporous adsorption resin column.

[0010] The preparation method of the above-mentioned Astragalus membranaceus extract includes: Astragalus membranaceus slices, soaked in honey at a honey-to-medicine mass ratio of (0.2-0.3):1, baked, pulverized, and extracted with deionized water at a material-to-liquid mass ratio of 1:(12-15), at 90℃-95℃, filtered, and the filtrate was concentrated under reduced pressure to 20%-30% of the filtrate volume. Ethanol was added to a final volume concentration of 65%-70%, allowed to stand, centrifuged, and the supernatant was collected. The supernatant was concentrated under reduced pressure to 10%-15% of the supernatant volume, loaded onto a Sephadex G-15 column, and washed with 15%-20% ethanol aqueous solution for 2-3 BV to remove impurities. The eluent was eluted with 50%-70% ethanol aqueous solution for 3-4 BV. The eluent was collected, concentrated under reduced pressure to remove ethanol, and lyophilized to obtain the Astragalus membranaceus extract.

[0011] In the above-mentioned preparation method of Astragalus membranaceus extract, the honey soaking time is 2h-3h; baking is carried out at 90℃-100℃ for 15min-25min; the particle size of the pulverized material is sieved through a 40-60 mesh sieve; the extraction time is 2h-3h; standing is carried out at 4℃-6℃ for 24h-30h; centrifugation is carried out at 8000rpm-9000rpm for 15min-20min; the pH value of the 50%-70% volume concentration ethanol aqueous solution is adjusted to 5.0-5.5 with acetic acid; and the temperature for vacuum concentration is 60℃-65℃.

[0012] The preparation method of the above-mentioned liposome-encapsulated Panax notoginseng total saponins-RGD peptide includes: preparing a solute according to the mass ratio of soybean lecithin:cholesterol = (4-5):(1-1.5), dissolving it in anhydrous ethanol to a solute concentration of 45mg / mL-50mg / mL to obtain an organic phase; adding a mixture of Panax notoginseng total saponins and RGD peptide at a mass ratio of (8-10):(3-5) to a phosphate buffer solution to a concentration of 15mg / mL-20mg / mL to obtain an aqueous phase; injecting the organic phase into the aqueous phase at a volume ratio of organic phase:aqueous phase = 1:(1-1.5), stirring, rotary evaporating to remove ethanol, obtaining a concentrated solution, sonicating with a probe, adding trehalose, and lyophilizing to obtain liposome-encapsulated Panax notoginseng total saponins-RGD peptide.

[0013] In the above method for preparing liposome-encapsulated Panax notoginseng total saponins-RGD peptides, the pH of the phosphate buffer solution is 7.4-7.6; the organic phase is injected into the aqueous phase at 55℃-60℃; stirring is performed at 600rpm-800rpm for 30min-50min; the rotary evaporation temperature is 55℃-60℃; the probe is used for ultrasonication with a 200W-250W probe for 8min-12min, controlling the average particle size to be below 120nm; and the amount of trehalose added is 5wt%-8wt% to the final concentration of the concentrate.

[0014] The preparation method of the above-mentioned honeysuckle-mac extract includes: mixing honeysuckle powder and maca root powder at a mass ratio of (3-5):(1-1.7) to obtain a mixed powder; adding deionized water, adjusting the pH to 5.0-5.5 with acetic acid, adding cellulase, and enzymatically hydrolyzing at 55℃-60℃ for 2-3 hours; adjusting the pH to 6.5-7.0 with dilute alkali, adding fig protease and papain, and enzymatically hydrolyzing at 55℃-60℃ for 2-3 hours; and heating for extraction. Centrifuge to obtain supernatant, concentrate under reduced pressure to 20%–30% of the supernatant volume to obtain concentrated solution, load onto HPD722 macroporous adsorption resin column, wash with water for 2–3 BV to remove impurities, wash with 30%–35% volume concentrated ethanol aqueous solution for 1–2 BV to remove impurities, elute with 60%–65% volume concentrated ethanol aqueous solution for 3–5 BV, collect the eluent, concentrate under reduced pressure to remove ethanol, freeze dry to obtain honeysuckle-mac extract.

[0015] In the above preparation method of honeysuckle-mac extract, the particle size of honeysuckle powder and maca root powder is sieved through a 40-60 mesh sieve; the amount of deionized water is 8 to 12 times the mass of the mixed powder; the amount of cellulase added is 0.5% to 1% of the mass of the mixed powder; the amounts of fig protease and papain added are both 0.5% to 1% of the mass of the mixed powder; the heating extraction is carried out at 80℃ to 85℃ for 2 to 3 hours; the centrifugation is carried out at 8000 rpm to 9000 rpm for 15 to 20 minutes; and the temperature for vacuum concentration is 60℃ to 65℃.

[0016] The preparation method of the above-mentioned asiaticoside-hydroxypropyl-β-cyclodextrin inclusion complex includes: preparing a mixture of asiaticoside and hydroxypropyl-β-cyclodextrin at a mass ratio of 1:(2-2.5), dissolving it in an aqueous ethanol solution until the mixture concentration is 10mg / mL-15mg / mL, sonicating with a probe, refrigerating, and freeze-drying to obtain the asiaticoside-hydroxypropyl-β-cyclodextrin inclusion complex.

[0017] In the above preparation method of asiaticoside-hydroxypropyl-β-cyclodextrin inclusion complex, the ethanol aqueous solution is a 30% to 35% volume concentration ethanol aqueous solution; the probe ultrasound is performed at 20℃ to 25℃ with a 350W to 400W probe for 40 to 60 minutes; and the refrigeration is performed at 4℃ to 6℃ for 12 to 16 hours.

[0018] The preparation method of the above-mentioned drug for promoting skin damage repair and healing includes the following steps: according to the mass fractions, the astragalus extract, liposome-encapsulated Panax notoginseng total saponins-RGD peptide, honeysuckle-maca extract, asiaticoside-hydroxypropyl-β-cyclodextrin inclusion complex and dipotassium glycyrrhizate are mixed evenly to obtain a mixed drug.

[0019] The above-prepared mixed drug, combined with pharmaceutically available excipients, is used to formulate a dressing for promoting the repair and healing of skin damage.

[0020] This invention provides a drug for promoting skin damage repair and healing, and its preparation method, with the following beneficial effects:

[0021] I. This invention, through a scientific combination of ingredients and a rigorous preparation process, comprehensively solves the problems of traditional Chinese medicine external application in terms of safety, therapeutic efficacy, and control of skin pigmentation. It removes impurities that cause allergies, achieving a comprehensive effect of reducing the risk of allergies and skin irritation, effectively promoting skin damage healing, and effectively inhibiting melanin deposition, thus effectively improving the efficacy of "safety, efficient healing, and low pigmentation deposition."

[0022] Second, astragalus is first soaked in honey, a process that not only corrects the taste of the medicine but also improves extraction efficiency and enhances efficacy. Subsequent roasting and processing promotes the transformation of the internal components of astragalus, enhancing its stability and effectiveness. In the extraction stage, specific temperature and time controls ensure the full dissolution of the active ingredients in astragalus. Then, purification is achieved using a Sephadex G-15 column, utilizing its molecular sieve principle to effectively remove sensitizing impurities while retaining components that enhance red blood cell membrane stability. This series of precisely controlled parameters ensures high purity and stable activity of the extracted components, significantly improving the safety of medication.

[0023] III. Liposome Encapsulation of Panax Notoginseng Total Saponins-RGD Peptide: During the construction of the liposome carrier, a specific mixing ratio forms a stable phospholipid bilayer structure. This structure acts like a miniature protective membrane, encapsulating the Panax Notoginseng total saponins and RGD peptide, isolating them from immune cells, effectively preventing immune responses, and delaying the degradation of RGD peptide during skin application. During preparation, ultrasound is used to control the liposome particle size, improving absorption. The sustained-release properties of liposomes allow for the continuous and slow release of Panax Notoginseng total saponins-RGD peptide, providing a stable and lasting signal for cell proliferation, promoting cell division and growth.

[0024] IV. In extracting the effective components of honeysuckle and maca, a specific ratio of compounding is used to enhance synergistic effects. Cellulase is employed to fully enzymatically hydrolyze the plant cell walls, releasing more active ingredients. A dual enzymatic hydrolysis method using fig protease and papain is used to obtain characteristic small molecule peptides, enhancing the synergistic effect of skin repair. The hydrolyzed products are purified using HPD722 macroporous adsorption resin. Utilizing the differences in the resin's adsorption capacity for different components, substances that irritate the skin are removed. By optimizing these enzymatic hydrolysis and purification parameters, the anti-inflammatory and repair-promoting activities of the extract are preserved to the greatest extent, providing strong support for skin damage repair.

[0025] V. The asiaticoside-hydroxypropyl-β-cyclodextrin inclusion complex can improve the stability of asiaticoside, allowing for sustained and gradual release, effectively inhibiting melanin synthesis, and reducing skin pigmentation.

[0026] VI. Dipotassium glycyrrhizate contains a unique carboxyl group and potassium ion in its molecular structure, which can interact with the active ingredients in Astragalus membranaceus extract. When it works synergistically with Astragalus membranaceus extract, it forms a protective film on the surface of erythrocyte membranes, enhancing cell membrane stability, reducing the risk of erythrocyte rupture under drug action, and further improving drug safety.

[0027] VII. Liposome-encapsulated Panax notoginseng total saponins-RGD peptides can continuously release active ingredients, activate intracellular proliferation signaling pathways, and promote cell mitosis. The active peptides in honeysuckle-maca extract regulate inflammatory responses, attracting macrophages, fibroblasts, and other cells to the damaged site, providing the necessary cellular basis for wound repair. These two components work synergistically to accelerate angiogenesis, delivering sufficient nutrients to the damaged site, and promote epithelial cell migration, covering the wound and significantly improving wound healing efficiency.

[0028] 8. The asiaticoside-hydroxypropyl-β-cyclodextrin inclusion complex inhibits tyrosinase activity, blocking melanin production at a key enzymatic stage of melanin synthesis. Simultaneously, the active substances in Astragalus membranaceus extract and Lonicera japonica-Maca extract can regulate the function of immune cells such as macrophages, reducing the release of melanin-promoting factors. The synergistic effect of these multiple components, through both enzyme activity inhibition and immune regulation, jointly prevents pigmentation, achieving a dual synergistic effect of "promoting healing and inhibiting pigmentation."

[0029] 9. Synergistic Proportions: The proportions of each component in the drug are carefully designed. For example, the mass fractions of Astragalus membranaceus extract, liposome-encapsulated components, and honeysuckle-maca extract are strictly controlled within specific ranges. This precise proportion control avoids competitive inhibition or adverse interactions between components. For instance, if the ratio of chlorogenic acid and asiaticoside is inappropriate, they will compete for the same target, leading to reduced efficacy. A reasonable ratio ensures that each component can fully exert its own efficacy, synergistically rather than canceling each other out, thereby maximizing the overall efficacy of the drug. Detailed Implementation

[0030] The present invention will be further described below with reference to specific implementation examples, but the present invention is not limited to these embodiments.

[0031] Example 1

[0032] A drug for promoting the repair and healing of skin damage comprises the following raw materials in parts by weight: 28 parts of roasted Astragalus membranaceus extract, 13 parts of liposome-encapsulated Panax notoginseng total saponins-RGD peptide, 14 parts of honeysuckle-maca extract, 8 parts of asiaticoside-hydroxypropyl-β-cyclodextrin inclusion complex, and 4 parts of dipotassium glycyrrhizate.

[0033] The preparation method of Astragalus membranaceus extract includes: Astragalus membranaceus slices, soaked in honey for 2.5 hours at a honey-to-medicine mass ratio of 0.25:1, baked at 95℃ for 20 minutes, pulverized and passed through a 50-mesh sieve, deionized water added at a material-to-liquid mass ratio of 1:13, extracted at 92℃ for 2.5 hours, filtered, and the filtrate was concentrated under reduced pressure at 62℃ to 25% of the filtrate volume. Ethanol was added to a final volume concentration of 68%, and the mixture was allowed to stand at 5℃ for 26 hours. After centrifugation at 8500 rpm for 18 minutes, the supernatant was collected and concentrated under reduced pressure at 62℃ to 13% of the supernatant volume. The supernatant was loaded onto a Sephadex G-15 column, eluted with 18% ethanol aqueous solution for 2.5 BV to remove impurities, and eluted with 60% ethanol aqueous solution (pH adjusted to 5.2 with acetic acid) for 3.5 BV. The eluent was collected, concentrated under reduced pressure at 62℃ to remove ethanol, and lyophilized to obtain Astragalus membranaceus extract.

[0034] The preparation method of liposome-encapsulated Panax notoginseng total saponins-RGD peptide includes: preparing a solute according to the mass ratio of soybean lecithin:cholesterol = 4.5:1.2, dissolving it in anhydrous ethanol to a solute concentration of 48 mg / mL to obtain an organic phase; adding a mixture of Panax notoginseng total saponins and RGD peptide at a mass ratio of 9:4 to a pH 7.5 phosphate buffer solution to a concentration of 18 mg / mL to obtain an aqueous phase; injecting the organic phase into the aqueous phase at a volume ratio of organic phase:aqueous phase = 1:1.3, stirring at 700 rpm for 40 min, removing ethanol by rotary evaporation at 58 °C to obtain a concentrated solution, sonicating with a 200W probe for 10 min, adding trehalose to a final concentration of 6 wt%, and lyophilizing to obtain liposome-encapsulated Panax notoginseng total saponins-RGD peptide.

[0035] The preparation method of honeysuckle-mac extract includes: mixing honeysuckle powder and maca root powder (passed through a 50-mesh sieve) at a mass ratio of 4:1.3 to obtain a mixed powder; adding 10 times the mass of deionized water to the mixed powder, adjusting the pH to 5.2 with acetic acid, adding 0.8% (by mass) of cellulase to the mixed powder, enzymatically hydrolyzing at 58℃ for 2.5 hours, adjusting the pH to 6.8 with dilute alkali, adding 0.8% (by mass) each of fig protease and papain to the mixed powder, enzymatically hydrolyzing at 58℃ for 2.5 hours; heating... Extract at 82℃ for 2.5 h, centrifuge at 8500 rpm for 18 min to obtain supernatant, concentrate under reduced pressure at 62℃ to 25% of the supernatant volume to obtain concentrated solution, load onto HPD722 macroporous adsorption resin column, wash with water for 2.5 BV to remove impurities, wash with 32% volume concentrated ethanol aqueous solution for 1.5 BV to remove impurities, elute with 62% volume concentrated ethanol aqueous solution for 4 BV, collect the eluent, concentrate under reduced pressure at 62℃ to remove ethanol, freeze dry to obtain honeysuckle-maca extract.

[0036] The preparation method of the asiaticoside-hydroxypropyl-β-cyclodextrin inclusion complex includes: preparing a mixture of asiaticoside and hydroxypropyl-β-cyclodextrin at a mass ratio of 1:2.3, dissolving it in a 32% volume concentration ethanol aqueous solution until the mixture concentration reaches 12 mg / mL, sonicating at 23℃ with a 350W probe for 50 min, refrigerating at 5℃ for 14 h, and freeze-drying to obtain the asiaticoside-hydroxypropyl-β-cyclodextrin inclusion complex.

[0037] Example 2

[0038] A drug for promoting the repair and healing of skin damage comprises the following raw materials in parts by weight: 25 parts of roasted Astragalus membranaceus extract, 15 parts of liposome-encapsulated Panax notoginseng total saponins-RGD peptide, 12 parts of honeysuckle-maca extract, 10 parts of asiaticoside-hydroxypropyl-β-cyclodextrin inclusion complex, and 3 parts of dipotassium glycyrrhizate.

[0039] The preparation method of Astragalus membranaceus extract includes: Astragalus membranaceus slices, soaked in honey for 2 hours at a honey-to-medicine mass ratio of 0.3:1, baked at 100℃ for 15 minutes, pulverized and passed through a 60-mesh sieve, added with deionized water at a material-to-liquid mass ratio of 1:12, extracted at 95℃ for 2 hours, filtered, and the filtrate was concentrated under reduced pressure at 65℃ to 20% of the filtrate volume, ethanol was added to a final volume concentration of 70%, allowed to stand at 4℃ for 30 hours, centrifuged at 8000 rpm for 20 minutes, the supernatant was collected, concentrated under reduced pressure at 60℃ to 15% of the supernatant volume, loaded onto a Sephadex G-15 column, eluted with 15% ethanol aqueous solution for 3BV to remove impurities, eluted with 50% ethanol aqueous solution (pH adjusted to 5.5 with acetic acid), the eluent was collected, concentrated under reduced pressure at 65℃ to remove ethanol, and lyophilized to obtain Astragalus membranaceus extract.

[0040] The preparation method of liposome-encapsulated Panax notoginseng total saponins-RGD peptide includes: preparing a solute according to the mass ratio of soybean lecithin:cholesterol = 4:1.5, dissolving it in anhydrous ethanol to a solute concentration of 45 mg / mL to obtain an organic phase; adding a mixture of Panax notoginseng total saponins and RGD peptide at a mass ratio of 10:3 to a pH 7.6 phosphate buffer solution to a concentration of 15 mg / mL to obtain an aqueous phase; injecting the organic phase into the aqueous phase at a volume ratio of organic phase:aqueous phase = 1:1.5, stirring at 800 rpm for 30 min, rotary evaporating at 60°C to remove ethanol, obtaining a concentrated solution, sonicating with a 200W probe for 12 min, adding trehalose to a final concentration of 5 wt%, and lyophilizing to obtain liposome-encapsulated Panax notoginseng total saponins-RGD peptide.

[0041] The preparation method of honeysuckle-mac extract includes: mixing honeysuckle powder and maca root powder (passed through a 60-mesh sieve) at a mass ratio of 3:1.7 to obtain a mixed powder; adding 8 times the mass of deionized water to the mixed powder, adjusting the pH to 5.5 with acetic acid, adding 0.5% (by mass) of cellulase to the mixed powder, and enzymatically hydrolyzing at 60℃ for 2 hours; adjusting the pH to 7.0 with dilute alkali, adding 0.5% (by mass) of fig protease and papain to the mixed powder, and enzymatically hydrolyzing at 60℃ for 2 hours; heating to 85℃ for 2 hours of extraction, centrifuging at 9000 rpm for 15 minutes to obtain the supernatant, concentrating under reduced pressure at 65℃ to 20% of the supernatant volume to obtain the concentrate, loading the concentrate onto an HPD722 macroporous adsorption resin column, rinsing with water for 3 BV to remove impurities, rinsing with 30% (by volume) concentrated ethanol aqueous solution for 2 BV to remove impurities, eluting with 60% (by volume) concentrated ethanol aqueous solution for 5 BV, collecting the eluent, concentrating under reduced pressure at 60℃ to remove ethanol, and lyophilizing to obtain the honeysuckle-mac extract.

[0042] The preparation method of the asiaticoside-hydroxypropyl-β-cyclodextrin inclusion complex includes: preparing a mixture of asiaticoside and hydroxypropyl-β-cyclodextrin at a mass ratio of 1:2.5, dissolving it in a 30% volume concentration ethanol aqueous solution until the mixture concentration reaches 15 mg / mL, sonicating at 20℃ with a 400W probe for 40 min, refrigerating at 6℃ for 12 h, and freeze-drying to obtain the asiaticoside-hydroxypropyl-β-cyclodextrin inclusion complex.

[0043] Example 3

[0044] A drug for promoting the repair and healing of skin damage comprises the following raw materials in parts by weight: 30 parts of roasted Astragalus membranaceus extract, 11 parts of liposome-encapsulated Panax notoginseng total saponins-RGD peptide, 15 parts of honeysuckle-maca extract, 6 parts of asiaticoside-hydroxypropyl-β-cyclodextrin inclusion complex, and 5 parts of dipotassium glycyrrhizate.

[0045] The preparation method of Astragalus membranaceus extract includes: Astragalus membranaceus slices, soaked in honey for 3 hours at a honey-to-medicine mass ratio of 0.2:1, baked at 90℃ for 25 minutes, pulverized and passed through a 40-mesh sieve, added deionized water at a material-to-liquid mass ratio of 1:15, extracted at 90℃ for 3 hours, filtered, and the filtrate was concentrated under reduced pressure at 60℃ to 30% of the filtrate volume, ethanol was added to a final volume concentration of 65%, allowed to stand at 6℃ for 24 hours, centrifuged at 9000 rpm for 15 minutes, the supernatant was collected, concentrated under reduced pressure at 65℃ to 10% of the supernatant volume, loaded onto a Sephadex G-15 column, washed with 20% ethanol aqueous solution for 2 BV to remove impurities, and eluted with 70% ethanol aqueous solution (pH adjusted to 5.0 with acetic acid) for 4 BV, the eluent was collected, concentrated under reduced pressure at 60℃ to remove ethanol, and freeze-dried to obtain Astragalus membranaceus extract.

[0046] The preparation method of liposome-encapsulated Panax notoginseng total saponins-RGD peptide includes: preparing a solute according to the mass ratio of soybean lecithin:cholesterol = 5:1, dissolving it in anhydrous ethanol to a solute concentration of 50 mg / mL to obtain an organic phase; adding a mixture of Panax notoginseng total saponins and RGD peptide at a mass ratio of 8:5 to a pH 7.4 phosphate buffer solution to a concentration of 20 mg / mL to obtain an aqueous phase; injecting the organic phase into the aqueous phase at a volume ratio of organic phase:aqueous phase = 1:1, stirring at 600 rpm for 50 min, rotary evaporating at 55°C to remove ethanol, obtaining a concentrated solution, sonicating with a 250W probe for 8 min, adding trehalose to a final concentration of 8 wt%, and lyophilizing to obtain liposome-encapsulated Panax notoginseng total saponins-RGD peptide.

[0047] The preparation method of honeysuckle-mac extract includes: mixing honeysuckle powder and maca root powder (passed through a 40-mesh sieve) at a mass ratio of 5:1 to obtain a mixed powder; adding 12 times the mass of deionized water to the mixed powder, adjusting the pH to 5.0 with acetic acid, adding 1% (by mass) of cellulase to the mixed powder, and enzymatically hydrolyzing at 55℃ for 3 hours; adjusting the pH to 6.5 with dilute alkali, adding 1% (by mass) of fig protease and papain to the mixed powder, and enzymatically hydrolyzing at 55℃ for 3 hours; heating to 80℃ for 3 hours of extraction, centrifuging at 8000 rpm for 20 minutes to obtain the supernatant, concentrating under reduced pressure at 60℃ to 30% of the supernatant volume to obtain the concentrate, loading the concentrate onto an HPD722 macroporous adsorption resin column, rinsing with water for 2 BV to remove impurities, rinsing with 35% (by volume) concentrated ethanol aqueous solution for 1 BV to remove impurities, eluting with 65% (by volume) concentrated ethanol aqueous solution for 3 BV, collecting the eluent, concentrating under reduced pressure at 65℃ to remove ethanol, and lyophilizing to obtain the honeysuckle-mac extract.

[0048] The preparation method of the asiaticoside-hydroxypropyl-β-cyclodextrin inclusion complex includes: preparing a mixture of asiaticoside and hydroxypropyl-β-cyclodextrin at a mass ratio of 1:2, dissolving it in a 35% volume concentration ethanol aqueous solution until the mixture concentration reaches 10 mg / mL, sonicating at 25℃ with a 350W probe for 60 min, refrigerating at 4℃ for 16 h, and freeze-drying to obtain the asiaticoside-hydroxypropyl-β-cyclodextrin inclusion complex.

[0049] The preparation method of a drug for promoting skin damage repair and healing according to the above embodiments includes the following steps: according to the mass proportions of raw materials in each embodiment, the astragalus extract, liposome-encapsulated Panax notoginseng total saponins-RGD peptide, honeysuckle-mac extract, asiaticoside-hydroxypropyl-β-cyclodextrin inclusion complex and dipotassium glycyrrhizate are mixed evenly to obtain a mixed drug.

[0050] The mixed drugs prepared in the above embodiments are combined with pharmaceutically available excipients to form dressings for promoting the repair and healing of skin damage.

[0051] Comparative Example 1

[0052] The difference from Example 1 is that the Astragalus membranaceus extract was modified to 14 parts, and the honeysuckle-maca extract was modified to 28 parts.

[0053] Comparative Example 2

[0054] The difference from Example 1 is that the amount of Astragalus membranaceus extract was changed to 13 parts, and the amount of Panax notoginseng total saponins-RGD peptide encapsulated in liposomes was changed to 28 parts.

[0055] Comparative Example 3

[0056] The difference from Example 1 is that the amount of asiaticoside-hydroxypropyl-β-cyclodextrin inclusion complex was changed to 4 parts; and the amount of dipotassium glycyrrhizate was changed to 8 parts.

[0057] Comparative Example 4

[0058] The difference from Example 1 is that in the preparation method of Astragalus membranaceus extract, Astragalus membranaceus is not soaked in honey and baked; Astragalus membranaceus is directly pulverized and extracted with water.

[0059] Comparative Example 5

[0060] The difference from Example 1 is that in the preparation method of Astragalus membranaceus extract, Sephadex G-15 is replaced by dextran gel LH-20.

[0061] Comparative Example 6

[0062] The difference from Example 1 is that in the preparation method of liposome-encapsulated Panax notoginseng total saponins-RGD peptide, the mass ratio of Panax notoginseng total saponins to RGD peptide is modified to 4:9.

[0063] Comparative Example 7

[0064] The difference from Example 1 is that in the preparation method of honeysuckle-mac extract, the mass ratio of honeysuckle powder to maca root powder is modified to 1.3:4.

[0065] Comparative Example 8

[0066] The difference from Example 1 is that fig protease is not added in the preparation method of honeysuckle-maca extract.

[0067] Comparative Example 9

[0068] The difference from Example 1 is that in the preparation method of honeysuckle-mac extract, papain is replaced by bromelain.

[0069] Comparative Example 10

[0070] The difference from Example 1 is that in the preparation method of honeysuckle-maca extract, bromelain is used instead of fig protease.

[0071] Comparative Example 11

[0072] The difference from Example 1 is that in the preparation method of honeysuckle-maca extract, the HPD722 macroporous adsorption resin column is replaced by D101 macroporous adsorption resin.

[0073] Comparative Example 12

[0074] The difference from Example 1 is as follows: the Astragalus membranaceus extract was modified to 14 parts, the honeysuckle-mac extract was modified to 28 parts, the asiaticoside-hydroxypropyl-β-cyclodextrin inclusion complex was modified to 4 parts, the dipotassium glycyrrhizate was modified to 8 parts, the mass ratio of total Panax notoginseng saponins to RGD peptide was modified to 4:9, and the mass ratio of honeysuckle powder to maca root powder was modified to 1.3:4.

[0075] The raw materials used in the above embodiments and comparative examples are as follows: Sephadex G-15 is from Shanghai Yuanye Biotechnology Co., Ltd., model S14030. Soybean lecithin is from Zhengzhou Wanruida Chemical Products Co., Ltd., pharmaceutical grade. Cholesterol is from Beijing Dingguo Changsheng Biotechnology Co., Ltd., pharmaceutical grade. Trehalose is from Xi'an Lavia Biotechnology Co., Ltd., pharmaceutical grade. Panax notoginseng total saponins are from Wuhan Fengzhulin Chemical Technology Co., Ltd., active pharmaceutical ingredient. Cellulase is from Hefei Shengrun Biological Products Co., Ltd., enzyme activity 100,000 U / g. Fig protease is from Hanzhong Hansuyuan Biotechnology Co., Ltd., enzyme activity 100,000 U / g. Papain is from Sichuan Huatang Jurui Biotechnology Co., Ltd., enzyme activity 100,000 U / g. HPD722 macroporous adsorption resin is from Shanghai Yuanye Biotechnology Co., Ltd., model S25180. Centella asiatica glycoside is from Hanzhong Hansuyuan Biotechnology Co., Ltd., pharmaceutical grade. Hydroxypropyl-β-cyclodextrin is from Shandong Zhonghuan Zhongjie Biotechnology Co., Ltd., pharmaceutical grade. RGD peptide is an arginine-glycine-aspartic peptide, sourced from Chengdu Yunxi Chemical Co., Ltd., a pharmaceutical intermediate. Dipotassium glycyrrhizate is sourced from Jiangsu Orlistat Pharmaceutical Co., Ltd., pharmaceutical grade. LH-20 dextran gel is sourced from Shanghai Yuanye Biotechnology Co., Ltd., model S14037. D101 macroporous adsorption resin is sourced from Shanghai Yuanye Biotechnology Co., Ltd., model S14161. Bromelain is sourced from Shaanxi Hehua Beikang Biotechnology Co., Ltd., with an enzyme activity of 100,000 U / g.

[0076] 1. Safety testing:

[0077] 1.1 Hemolysis detection:

[0078] Sample preparation: Take 10 mg of mixed drug powder, place it in a centrifuge tube, add 1.0 mL of PBS (pH 7.4), vortex for 10 min, filter through a 0.22 μm filter membrane, centrifuge at 3000 rpm for 10 min (4℃), take the supernatant, and dilute with PBS to a gradient concentration of 0.5 mg / mL, 1 mg / mL, 2 mg / mL, and 4 mg / mL.

[0079] Methods and procedures: Take anticoagulated blood (EDTA anticoagulated) from healthy individuals, wash it 3 times with physiological saline (centrifuged at 1500 rpm for 10 min each time at 4℃), and take red blood cells to prepare a 2% (v / v) suspension with physiological saline.

[0080] Reaction system:

[0081]

[0082] The experimental group was set up with 3 replicates. After incubating in a 37℃ water bath for 2 hours, the sample was centrifuged at 1500 rpm for 10 minutes (4℃). The supernatant was collected, and the absorbance value A was measured at 540 nm. Hemolysis rate % = (A experimental group - A negative control) / (A positive control - A negative control) × 100%. A hemolysis rate <5% is considered safe. The test results are shown in Table 1 below.

[0083] Table 1. Results of hemolysis test (hemolysis rate % range, 3 replicates).

[0084]

[0085] 1.2 Sensitization (h-CLAT) Detection:

[0086] Sample preparation: Stock solution: 10 mg / mL (RPMI 1640 medium containing 0.1% DMSO); Working solution: diluted to 50 μg / mL and 100 μg / mL with RPMI 1640 medium containing 10% FBS (filtered for sterilization).

[0087] Solvent control: RPMI 1640 medium containing 0.1% DMSO;

[0088] Positive control: 1mM NiSO4.

[0089] Methods and procedures: THP-1 cells were inoculated at 1×10⁻⁶ cells per cell line. 6 Cells / mL (RPMI 1640 + 10% FBS) were seeded into 24-well plates, 1 mL / well. The 24-well plates were incubated at 37°C with 5% CO2 saturated humidity for 24 h. After centrifugation (1500 rpm × 5 min, 4°C), the supernatant was discarded, and the cells were washed once with PBS. 1 mL / well of different concentrations of working solution (experimental group), solvent control, and positive control were added, with 3 replicates for the experimental group. Cells were cultured for another 24 h. Cell collection: The cell suspension was transferred to flow cytometry tubes. Centrifugation was performed at 1500 rpm for 5 min (4°C), the supernatant was discarded, and the cells were washed twice with PBS (1 mL PBS added each time, centrifugation followed by discarding the supernatant). The cells were resuspended in 100 μL PBS. Fluorescently labeled antibodies were added: 5 μL anti-human CD86-FITC and 5 μL anti-human CD54-PE. The plates were incubated on ice for 30 min in the dark. The cells were washed twice with PBS (1 mL PBS added each time, centrifugation followed by discarding the supernatant). Cells were resuspended in 300 μL PBS and analyzed by flow cytometry. A positive result was defined as RFI (CD86) ≥ 150% and RFI (CD54) ≥ 200%, or RFI (CD86) ≥ 200% and RFI (CD54) ≥ 150%; otherwise, a negative result (no sensitization) was defined as the positive result. The results are shown in Table 2 below.

[0090] Table 2. Sensitization test results (RFI range, 3 replicates)

[0091]

[0092] 2. Efficacy testing:

[0093] 2.1 Cell proliferation detection (CCK-8 assay):

[0094] Sample preparation: 100 μg / mL drug solution (prepared with 0.9% physiological saline and sterilized by filtration).

[0095] Detection method: Human epidermal keratinocytes were sampled at a concentration of 3 × 10⁻⁶. 4 Cells / well (100μL DMEM+10%FPS) were seeded in 96-well plates and cultured at 37°C in a cell culture incubator with 5% CO2 saturated humidity for 24 hours to adhere to the plates. The old culture medium was discarded and 100μL of drug solution was added.

[0096] A control group was also set up:

[0097]

[0098] Five replicates were made in each group (experimental group). The cells were cultured for another 48 hours, then the culture medium was discarded. 100 μL of fresh culture medium containing 10% CCK-8 was added to each well, and the cells were incubated for another 2 hours in the dark. The absorbance (OD) value was measured at 450 nm. Cell proliferation rate (%) was calculated as: (OD value of experimental group - OD value of drug background control group - OD value of blank group) / (OD value of negative control group - OD value of blank group) × 100%. The results are shown in Table 3 below.

[0099] Table 3. Cell proliferation detection results (proliferation rate range, 5 replicates).

[0100]

[0101] 2.2 Detection of melanin synthesis inhibition:

[0102] Sample preparation: Stock solution of drug: 10 mg / mL (DMEM basal medium containing 0.1% DMSO); Working solution: diluted to 100 μg / mL with DMEM basal medium containing 10% FBS (filtered for sterilization).

[0103] Set up a control group:

[0104]

[0105] Methods and procedures: B16F10 cells were stored at a density of 5 × 10⁶ cells / cells. 4Cells / mL were seeded into 96-well plates at 100 μL / well and cultured at 37℃ in a 5% CO2 saturated humidity incubator for 24 h to allow adhesion. The old culture medium was discarded. 100 μL of working solution containing 100 nM α-MSH (in 5 replicates) was added to each well, with a control group included. Cultured for another 48 h. The culture medium was discarded. The cells were washed once with PBS, and 100 μL of 1 mol / L NaOH solution (containing 10% DMSO) was added to each well. The cells were incubated at 80℃ for 1 h (to dissolve melanin). The absorbance (OD) value was measured at 405 nm using a microplate reader. Melanin synthesis inhibition rate (%) = [1 - (OD drug group - OD unstimulated group) / (α-MSH stimulated group - OD unstimulated group)] × 100%; values ​​are after deducting the background value of the blank group. The results are shown in Table 4 below.

[0106] In this experiment, the ΔOD of the α-MSH stimulation group and the OD non-stimulated group was equal to the OD solvent control group minus the OD non-stimulated group; ΔOD > 0.5, indicating effective stimulation.

[0107] Table 4. Results of melanin synthesis inhibition detection (inhibition rate range, 5 replicates)

[0108]

[0109] In Examples 1 to 3, the Astragalus membranaceus extract was processed with honey and purified using Sephadex G-15 to remove sensitizing impurities while retaining components that enhance erythrocyte membrane stability. It also synergistically reduced erythrocyte rupture with dipotassium glycyrrhizate. The liposome-encapsulated Panax notoginseng total saponins-RGD peptides, protected by a phospholipid bilayer, prevented immune cell irritation and, simultaneously, provided sustained-release activity, offering a stable signal for cell proliferation. The Lonicera japonica-Maca extract, purified using dual enzymatic hydrolysis (cellulase + fig protease + papain) and HPD722 resin, removed irritants such as tannins while retaining active ingredients, including small molecule peptides. The asiaticoside-hydroxypropyl-β-cyclodextrin inclusion complex, with its hydrophobic cavity stabilizing the structure, inhibited tyrosinase activity and synergistically inhibited melanin synthesis with other components.

[0110] Comparative Example 1 (Reduced Astragalus membranaceus extract, increased Honeysuckle-Mac extract): The reduced Astragalus membranaceus extract resulted in insufficient membrane-stabilizing components (such as astragaloside), weakening its protective effect on erythrocyte membranes. The excessive Honeysuckle-Mac extract led to an overabundance of chlorogenic acid, which binds to erythrocyte membrane phospholipids, disrupting membrane structure. This excessive Honeysuckle-Mac extract also contained excessive amounts of large-molecule sensitizing impurities that could trigger immune responses; simultaneously, chlorogenic acid competed with asiaticoside for binding targets, reducing the melanin-inhibiting effect.

[0111] Comparative Example 2 (reduced Astragalus membranaceus, increased liposome-encapsulated Panax notoginseng saponins-RGD peptide): Insufficient Astragalus membranaceus resulted in a lack of protection for the erythrocyte membrane; excessive liposomes increased the osmotic pressure of the solution, leading to erythrocyte shrinkage and rupture. Excessive liposome-encapsulated Panax notoginseng saponins-RGD peptides were easily recognized by immune cells, triggering an immune response; furthermore, excessive components interfered with normal cellular physiological processes and affected cell proliferation signal transduction.

[0112] Comparative Example 3 (decreased asiaticoside-hydroxypropyl-β-cyclodextrin inclusion complex, increased dipotassium glycyrrhizate): Excessive dipotassium glycyrrhizate interferes with normal cellular physiological functions and affects erythrocyte membrane stability. Decreased asiaticoside reduces the inhibitory effect on melanin synthesis; excessive dipotassium glycyrrhizate affects the synergistic effect of other components and interferes with cell proliferation signaling pathways.

[0113] Comparative Example 4 (Astragalus extract without honey soaking and baking): Since the processed Astragalus was not soaked in honey and baked, the types and contents of its active ingredients changed, making it unable to effectively maintain erythrocyte membrane stability. Untreated Astragalus extract retains more sensitizing impurities, easily triggering immune responses; simultaneously, the alteration of active ingredients affects its effects on promoting cell proliferation and inhibiting melanin synthesis.

[0114] Comparative Example 5 (Sephadex G-15 replaced with dextran gel LH-20): Different gels exhibited varying selectivity in separating components from the extract. The composition of the Astragalus membranaceus extract separated by dextran gel LH-20 changed, affecting its synergistic effect with other components in protecting the erythrocyte membrane. The altered extract composition led to increased residual sensitizing components, triggering a stronger immune response; simultaneously, changes in the proportion of active ingredients affected cell proliferation and melanin inhibition.

[0115] Comparative Example 6 (Change in the mass ratio of total Panax notoginseng saponins to RGD peptides): Changes in the ratio affect the encapsulation effect of liposomes and the release of active ingredients, and alter the drug's effect on the erythrocyte membrane; an improper ratio can affect the structural stability of liposomes and stimulate immune cells; at the same time, an imbalance in the ratio of active ingredients can interfere with cell proliferation signals and the melanin inhibition process.

[0116] Comparative Example 7 (Change in the mass ratio of honeysuckle to maca): Changes in the raw material ratio altered the composition and activity of the extract, affecting its synergistic effect with other components in maintaining erythrocyte membrane stability. Changes in the extract composition led to an increase in sensitizing substances, triggering an immune response; simultaneously, changes in the proportion of active ingredients affected anti-inflammatory effects and melanin inhibition, thereby impacting cell proliferation.

[0117] Comparative Example 8 (Honeysuckle-Maca Extract without Fig Protease): The absence of fig protease affects the enzymatic hydrolysis and extraction of components in the extract, altering the peptide sequence of the final extract and affecting hemolysis. Incomplete enzymatic hydrolysis leads to residual allergens, triggering an immune response; simultaneously, the reduction in effective components in the extract decreases the effects of promoting cell proliferation and inhibiting melanin synthesis.

[0118] Comparative Example 9 (papain replaced with bromelain): Different proteases have different substrates and effects. After bromelain was replaced, the composition and activity of the peptide extract changed, affecting hemolysis. Changes in the extract composition can introduce new sensitizing substances, triggering an immune response; at the same time, changes in the active ingredients can affect cell proliferation signaling and melanin inhibition effects.

[0119] Comparative Example 10 (fig protease replaced with bromelain): Replacing fig protease with bromelain altered the composition of the extract, affecting its synergistic effect with other components in maintaining erythrocyte membrane stability. The sensitizing components in the extract increased, triggering a stronger immune response; furthermore, changes in the proportion of active ingredients affected cell proliferation and melanin inhibition.

[0120] Comparative Example 11 (HPD722 macroporous adsorption resin replaced with D101): Different resins have different adsorption and elution capacities for components in the extract. The composition of the extract obtained with D101 macroporous adsorption resin is altered, affecting hemolysis. More sensitizing components may remain in the extract, triggering an immune response; at the same time, the loss of effective components will reduce the effects of promoting cell proliferation and inhibiting melanin synthesis.

[0121] Comparative Example 12 (Multiple Factor Changes): Changes in the proportions and components of multiple raw materials severely disrupted the formula balance. The components were unable to synergistically maintain the stability of the erythrocyte membrane, resulting in a significantly enhanced destructive effect on the erythrocyte membrane. The chaotic formula led to an increase in allergens, triggering an immune response; at the same time, the synergistic effect between the components was disrupted, and the cell proliferation and melanin inhibition effects were significantly reduced.

Claims

1. A drug for promoting the repair and healing of skin damage, characterized in that, The drug comprises the following raw materials in parts by weight: 25 to 30 parts of roasted Astragalus membranaceus extract, 11 to 15 parts of liposome-encapsulated Panax notoginseng total saponins-RGD peptide, 12 to 15 parts of honeysuckle-maca extract, 6 to 10 parts of asiaticoside-hydroxypropyl-β-cyclodextrin inclusion complex, and 3 to 5 parts of dipotassium glycyrrhizate. The roasted Astragalus extract is obtained by soaking Astragalus in honey, baking, extracting with deionized water, and purifying by adsorption and purification using a Sephadex G-15 column. In the liposome-encapsulated Panax notoginseng total saponins-RGD peptide, the mass ratio of Panax notoginseng total saponins to RGD peptide is (8-10):(3-5). The honeysuckle-mac extract is a product obtained by mixing honeysuckle powder and maca root powder in a mass ratio of (3-5):(1-1.7), hydrolyzing with cellulase, then hydrolyzing with fig protease and papain, and finally purifying by adsorption with HPD722 macroporous adsorption resin column.

2. The drug for promoting skin damage repair and healing according to claim 1, characterized in that, The preparation method of the processed Astragalus extract includes: Astragalus slices, soaked in honey at a honey-to-medicine mass ratio of (0.2-0.3):1, baked, pulverized, and extracted with deionized water at a material-to-liquid mass ratio of 1:(12-15), at 90℃-95℃, filtered, and the filtrate was concentrated under reduced pressure to 20%-30% of the filtrate volume. Ethanol was added to a final volume concentration of 65%-70%, allowed to stand, centrifuged, and the supernatant was collected. The supernatant was concentrated under reduced pressure to 10%-15% of the supernatant volume, loaded onto a Sephadex G-15 column, and washed with 15%-20% ethanol aqueous solution for 2-3 BV to remove impurities. The supernatant was eluted with 50%-70% ethanol aqueous solution for 3-4 BV. The eluent was collected, concentrated under reduced pressure to remove ethanol, and lyophilized to obtain the processed Astragalus extract.

3. The drug for promoting skin damage repair and healing according to claim 2, characterized in that, In the preparation method of Astragalus membranaceus extract, the honey soaking time is 2h-3h; the baking is carried out at 90℃-100℃ for 15min-25min; the particle size of the pulverized material is sieved through a 40-60 mesh sieve; the extraction time is 2h-3h; the standing time is 4℃-6℃ for 24h-30h; the centrifugation is carried out at 8000rpm-9000rpm for 15min-20min; the pH of the 50%-70% volume concentration ethanol aqueous solution is adjusted to 5.0-5.5 with acetic acid; and the temperature of the vacuum concentration is 60℃-65℃.

4. The drug for promoting skin damage repair and healing according to claim 1, characterized in that, The preparation method of the liposome-encapsulated Panax notoginseng total saponins-RGD peptide includes: preparing a solute according to the mass ratio of soybean lecithin:cholesterol = (4-5):(1-1.5), dissolving it in anhydrous ethanol to a solute concentration of 45 mg / mL to 50 mg / mL to obtain an organic phase; adding a mixture of Panax notoginseng total saponins and RGD peptide at a mass ratio of (8-10):(3-5) to a phosphate buffer solution to a concentration of 15 mg / mL to 20 mg / mL to obtain an aqueous phase; injecting the organic phase into the aqueous phase at a volume ratio of organic phase:aqueous phase = 1:(1-1.5), stirring, rotary evaporating to remove ethanol, obtaining a concentrated solution, sonicating with a probe, adding trehalose, and lyophilizing to obtain liposome-encapsulated Panax notoginseng total saponins-RGD peptide.

5. The drug for promoting skin damage repair and healing according to claim 4, characterized in that, In the method for preparing liposome-encapsulated Panax notoginseng total saponins-RGD peptide, the pH of the phosphate buffer solution is 7.4-7.6; the organic phase is injected into the aqueous phase at 55℃-60℃; the stirring is performed at 600rpm-800rpm for 30min-50min; the rotary evaporation temperature is 55℃-60℃; the ultrasound is performed using a 200W-250W probe for 8min-12min; and the amount of trehalose added is 5wt%-8wt% to the final concentration of the concentrate.

6. The drug for promoting skin damage repair and healing according to claim 1, characterized in that, The preparation method of the honeysuckle-mac extract includes: mixing honeysuckle powder and maca root powder at a mass ratio of (3-5):(1-1.7) to obtain a mixed powder; adding deionized water, adjusting the pH to 5.0-5.5 with acetic acid, adding cellulase, and enzymatically hydrolyzing at 55℃-60℃ for 2-3 hours; adjusting the pH to 6.5-7.0 with dilute alkali, adding fig protease and papain, and enzymatically hydrolyzing at 55℃-60℃ for 2-3 hours; and heating for extraction. Centrifuge to obtain supernatant, concentrate under reduced pressure to 20%–30% of the supernatant volume to obtain concentrated solution, load onto HPD722 macroporous adsorption resin column, wash with water for 2–3 BV to remove impurities, wash with 30%–35% volume concentrated ethanol aqueous solution for 1–2 BV to remove impurities, elute with 60%–65% volume concentrated ethanol aqueous solution for 3–5 BV, collect the eluent, concentrate under reduced pressure to remove ethanol, freeze dry to obtain honeysuckle-mac extract.

7. The drug for promoting skin damage repair and healing according to claim 6, characterized in that, In the preparation method of honeysuckle-maca extract, the particle size of both honeysuckle powder and maca root powder is sieved through a 40-60 mesh sieve; the amount of deionized water used is 8 to 12 times the mass of the mixed powder; the amount of cellulase added is 0.5% to 1% of the mass of the mixed powder; the amount of fig protease and papain added is 0.5% to 1% of the mass of the mixed powder; the heating extraction is performed at 80℃ to 85℃ for 2 to 3 hours; the centrifugation is performed at 8000 rpm to 9000 rpm for 15 to 20 minutes; and the temperature for vacuum concentration is 60℃ to 65℃.

8. The drug for promoting skin damage repair and healing according to claim 1, characterized in that, The preparation method of the asiaticoside-hydroxypropyl-β-cyclodextrin inclusion complex includes: preparing a mixture of asiaticoside and hydroxypropyl-β-cyclodextrin at a mass ratio of 1:(2-2.5), dissolving it in an aqueous ethanol solution until the mixture concentration is 10mg / mL-15mg / mL, sonicating with a probe, refrigerating, and freeze-drying to obtain the asiaticoside-hydroxypropyl-β-cyclodextrin inclusion complex.

9. The drug for promoting skin damage repair and healing according to claim 8, characterized in that, In the preparation method of the asiaticoside-hydroxypropyl-β-cyclodextrin inclusion complex, the ethanol aqueous solution is a 30% to 35% volume concentration ethanol aqueous solution; the probe ultrasound is performed at 20℃ to 25℃ with a 350W to 400W probe for 40 to 60 minutes; and the refrigeration is performed at 4℃ to 6℃ for 12 to 16 hours.

10. A method for preparing a medicament for promoting skin damage repair and healing as described in claim 1, characterized in that, The preparation method includes the following steps: according to the mass fractions, the astragalus extract, liposome-encapsulated Panax notoginseng total saponins-RGD peptide, honeysuckle-maca extract, asiaticoside-hydroxypropyl-β-cyclodextrin inclusion complex and dipotassium glycyrrhizate are mixed evenly to obtain a mixed drug.

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