A pharmaceutical composition for promoting wound healing and a preparation method and application thereof

Abstract

The application discloses a medicine composition for promoting wound healing and a preparation method and application thereof. The medicine composition comprises the following components in parts by weight: 1-10 parts of hemoglobin molecules, 1-5 parts of lipoic acid, 0.1-1 part of acetylcysteine, and 40-80 parts of a solvent; the hemoglobin molecules comprise at least one cysteine part and at least one histidine part, wherein the cysteine part comprises an acetyl group or an ethyl maleoyl group, and the histidine part comprises a benzimidazole derivative group. The application applies lipoic acid and acetylcysteine to the external medicine composition of the hemoglobin molecules modified by acetyl groups or ethyl maleoyl groups in combination, effectively relieves the irritant reaction caused by the hemoglobin modification to the skin through the synergistic antioxidant and tissue protection effects, and thus improves the safety and applicability of the medicine composition in skin wound treatment, and the medicine composition is suitable for treating multiple types of wounds such as external injuries, burns, postoperative wounds and ulcer wounds.

Description

A pharmaceutical composition for promoting wound healing, its preparation method and application Technical Field

[0001] This invention relates to the field of wound repair biotechnology, and in particular to a pharmaceutical composition for promoting wound healing, its preparation method, and its application. Background Technology

[0002] Wound repair is a common yet highly challenging process in clinical medicine, especially in complex wounds such as chronic wounds, burns, and diabetic foot ulcers, where tissue hypoxia, oxidative stress, and persistent inflammation often lead to delayed healing. Numerous studies have demonstrated that oxygen plays a crucial role in tissue repair processes such as cell proliferation, angiogenesis, and collagen synthesis. However, traditional wound treatments primarily focus on antibacterial, moisturizing, and occlusive therapies, failing to fundamentally alleviate the hypoxic state of the wound microenvironment.

[0003] Hemoglobin is a natural oxygen-carrying protein capable of reversibly binding to oxygen molecules and has been explored as a substitute for artificial blood or a tissue oxygen carrier. However, traditional hemoglobin preparations suffer from low oxygenation efficiency, poor stability, and easy oxidation into methemoglobin (Met-Hb), limiting their application in topical wound treatment. Furthermore, hemoglobin alone may cause local tissue irritation or immune responses. In addition, wound healing is accompanied by severe oxidative stress; excessive oxygen free radicals can easily deactivate hemoglobin, causing further damage to tissue cells and delaying the healing process.

[0004] Therefore, there is an urgent need for a novel composite topical drug composition that can simultaneously improve the local hypoxic environment, alleviate oxidative stress, and reduce tissue irritation in order to promote wound healing more efficiently and safely. Summary of the Invention

[0005] In view of the deficiencies in the prior art, the present invention proposes a pharmaceutical composition for promoting wound healing, its preparation method and application.

[0006] This invention provides a pharmaceutical composition for promoting wound healing, comprising, by weight, the following components:

[0007] 1-10 parts hemoglobin molecules, 1-5 parts lipoic acid, 0.1-1 part acetylcysteine, and 40-80 parts solvent;

[0008] The hemoglobin molecule includes at least one cysteine ​​moiety, wherein the cysteine ​​moiety includes an acetyl or ethyl maleic group; the hemoglobin molecule includes at least one cysteine ​​moiety and at least one histidine moiety, wherein the cysteine ​​moiety includes an acetyl or ethyl maleic group, and the histidine moiety includes a benzimidazole derivative group.

[0009] Benzimidazole derivatives possess certain hydrophobic and aromatic properties. After modification of hemoglobin molecules, they readily undergo π-π stacking interactions with skin barrier structures (such as keratin), thereby triggering mild inflammatory reactions or stinging sensations, especially at open wound sites. This invention, by combining lipoic acid and acetylcysteine, synergistically alleviates the skin irritation caused by benzimidazole-modified hemoglobin molecules, stabilizing cell membrane structure, reducing lipid peroxidation, and relieving skin redness, swelling, pain, and other irritation symptoms.

[0010] In some embodiments, the mass ratio of hemoglobin molecules to lipoic acid is (1-2):1. Lipoic acid molecules contain a disulfide ring structure, which can rapidly scavenge free radical reactions initiated by metal ions or free iron on the surface of hemoglobin, thereby protecting skin cells and inhibiting lipid peroxidation. Preferably, this invention combines hemoglobin molecules and lipoic acid at a mass ratio of (1-2):1 to ensure sufficient antioxidant capacity to match the potential oxidative burden of hemoglobin, preventing the accumulation of local oxidative stress. This forms a stable pharmaceutical composition system while ensuring its physicochemical properties are suitable for transdermal absorption and tissue compatibility.

[0011] This invention introduces two synergistic antioxidant components, lipoic acid and acetylcysteine, into the composition. On the one hand, they can directly remove excess reactive oxygen species around the wound, and on the other hand, they can indirectly increase glutathione synthesis by providing thiol donors, effectively alleviating oxidative stress and promoting inflammation control and tissue regeneration.

[0012] In some embodiments, the solvent is any one or more of water, physiological saline, and ethanol.

[0013] The present invention also provides a formulation comprising the pharmaceutical composition described above.

[0014] In some embodiments, the dosage form of the preparation is any one of spray, ointment, gel, cream, patch, emulsion, coating, foam, hydrogel dressing and wound dressing.

[0015] In some embodiments, the spray further includes 5 to 20 parts of a spray matrix selected from one or more film-forming agents, propellants, and humectants.

[0016] In some embodiments, the film-forming agent is selected from any one or more of polyvinylpyrrolidone, hydroxypropyl methylcellulose, sodium carboxymethyl cellulose, polyvinyl alcohol, chitosan, gelatin, carbomer, and hydroxypropyl cellulose.

[0017] In some embodiments, the propellant is selected from one or more of butane, isobutane, propane, 1,1,1,2-tetrafluoroethane, 1,1,1,2,3,3,3-heptafluoropropane, ethanol, and isopropanol.

[0018] The present invention also provides a method for preparing the pharmaceutical composition, comprising the following steps:

[0019] The modified hemoglobin molecules were dissolved in a buffer solution, and thioctic acid and acetylcysteine ​​were added. The mixture was stirred continuously, and after dissolution, a solvent was added to obtain the pharmaceutical composition.

[0020] In some embodiments, the buffer solution is any one of a phosphate buffer solution, a citric acid buffer solution, or an acetic acid buffer solution.

[0021] The present invention also provides the use of the pharmaceutical composition in the preparation of a medicament for promoting wound healing and repair.

[0022] In some embodiments, the wound or lesion is a burn, scald, soft tissue ulcer, or chronic erosion.

[0023] In summary, compared with the prior art, the present invention achieves the following technical effects:

[0024] 1. The pharmaceutical composition of the present invention uses benzimidazole derivative-modified hemoglobin molecules as the main functional component, which has good oxygen binding and release capabilities. The oxygenation rate can rapidly reach more than 90% within 1 minute after exposure to air, significantly improving the hypoxic state of local tissues in the wound and promoting cell activity and tissue repair.

[0025] 2. This invention combines lipoic acid and acetylcysteine ​​in a topical drug composition containing benzimidazole derivative-modified hemoglobin molecules. Through synergistic antioxidant and tissue protection effects, it effectively alleviates the irritation caused to the skin by hemoglobin modification, thereby improving the safety and applicability of the drug in the treatment of skin wounds. It is suitable for the treatment of various types of wounds such as trauma, burns, and postoperative wounds.

[0026] 3. The pharmaceutical composition of the present invention is in the form of an aqueous solution, with a simple formulation and synergistic compatibility of components. It can be prepared using conventional emulsification, mixing and filling processes, which is convenient for industrial production. Stability studies have verified that the product did not show obvious precipitation, stratification or component degradation within 12 months under normal temperature and light-protected conditions, indicating good product stability. Attached Figure Description

[0027] To more clearly illustrate the technical solutions of the embodiments of the present invention, the accompanying drawings used in the embodiments will be briefly introduced below. It should be understood that the following drawings only show some embodiments of the present invention and should not be regarded as a limitation on the scope. For those skilled in the art, other related drawings can be obtained based on these drawings without creative effort.

[0028] Figure 1 shows the change in the content of oxidized hemoglobin (Oxy-Hb) over time during the oxygenation process of hemoglobin molecules in air in Test Example 1 of the present invention. Detailed Implementation

[0029] To enable those skilled in the art to better understand the present invention, the technical solutions in the embodiments of the present invention are clearly and completely described. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort should fall within the scope of protection of the present invention.

[0030] In specific embodiments of the present invention, the pharmaceutical composition is applied in the form of a spray, which is convenient to use and suitable for the rapid treatment of large or irregular wounds. However, it should be understood that the pharmaceutical composition provided by the present invention is not limited to a spray formulation. Those skilled in the art can prepare it into various topical formulations according to actual needs without departing from the essential content of the present invention, including but not limited to ointments, gels, creams, plasters, lotions, coatings, foams, hydrogel dressings, wound films, etc. These formulations can better meet the needs of sustained drug release, local coverage, wound protection, and patient compliance in different clinical situations. Therefore, the scope of protection of the present invention should include all suitable formulations for applying the composition to topical treatment.

[0031] Unless otherwise specified, the experimental methods used in the following examples are conventional methods. Unless otherwise specified, all materials and reagents used are commercially available.

[0032] For details on the preparation and identification of the modified hemoglobin molecules, please refer to Patent No. ZL202411603238.3, Example 1.

[0033] Bovine hemoglobin molecule: Meilun Biotechnology, MB2760-1.

[0034] The method for preparing the wound-healing pharmaceutical composition of the present invention is as follows:

[0035] (1) Solution preparation: Add hemoglobin molecules to physiological saline and stir on a magnetic stirrer at a speed of 300-500 rpm to dissolve them. The temperature is controlled at 4-8℃ to prevent protein denaturation.

[0036] (2) Add lipoic acid and acetylcysteine ​​to the above solution in sequence, and stir continuously until all components are completely dissolved.

[0037] The above-mentioned drug composition was formulated into a spray for further testing:

[0038] Add the spray matrix to the above mixture, continue stirring until homogeneous, then add physiological saline. Use phosphate buffered saline (PBS, 0.01 mol / L) to control the pH in the range of 6.8 to 7.4.

[0039] The mixture was sterilized by using a vacuum filtration device and 0.22μm PES.

[0040] Example 1

[0041] The pharmaceutical composition of this embodiment comprises the following components in parts by weight:

[0042] 5 parts hemoglobin molecules, 3 parts lipoic acid, 0.5 parts acetylcysteine, 10 parts vinylpyrrolidone, and 60 parts physiological saline.

[0043] Example 2

[0044] The pharmaceutical composition of this embodiment comprises the following components in parts by weight:

[0045] 1 part hemoglobin, 1 part lipoic acid, 0.1 part acetylcysteine, 2 parts polyvinyl alcohol, 3 parts propylene glycol, and 60 parts physiological saline.

[0046] Example 3

[0047] The pharmaceutical composition of this embodiment comprises the following components in parts by weight:

[0048] 10 parts hemoglobin molecules, 5 parts lipoic acid, 1 part acetylcysteine, 2 parts polyvinyl alcohol, 3 parts propylene glycol, and 60 parts physiological saline.

[0049] Example 4

[0050] The pharmaceutical composition of this embodiment comprises the following components by weight: 3 parts hemoglobin molecules, 5 parts lipoic acid, 0.5 parts acetylcysteine, 10 parts vinylpyrrolidone, and 60 parts physiological saline.

[0051] Comparative Example 1

[0052] The pharmaceutical composition of this comparative example comprises the following components in parts by weight:

[0053] Five parts of unmodified bovine hemoglobin molecules, three parts of lipoic acid, 0.5 parts of acetylcysteine, ten parts of vinylpyrrolidone, and sixty parts of physiological saline.

[0054] Comparative Example 2

[0055] The pharmaceutical composition of this comparative example comprises the following components in parts by weight:

[0056] 5 parts hemoglobin molecules, 0.5 parts acetylcysteine, 10 parts vinylpyrrolidone, and 60 parts physiological saline.

[0057] Comparative Example 3

[0058] The pharmaceutical composition of this comparative example comprises the following components in parts by weight:

[0059] 5 parts hemoglobin molecules, 3 parts lipoic acid, 10 parts vinylpyrrolidone, and 60 parts physiological saline.

[0060] Comparative Example 4

[0061] The pharmaceutical composition of this comparative example comprises the following components in parts by weight:

[0062] Five parts hemoglobin molecules, ten parts vinylpyrrolidone, and sixty parts physiological saline.

[0063] Test Example 1: Analysis of Hemoglobin Molecular Oxygenation Curve

[0064] This test case verifies whether the hemoglobin molecules used in this application can rapidly bind with oxygen in the air and evaluates their oxygenation efficiency.

[0065] The content of oxidized hemoglobin (Oxy-Hb) in the hemoglobin molecules used in this application was determined using a blood gas analyzer (GEM OPL).

[0066] As shown in Figure 1, within one minute of the reaction starting, the Oxy-Hb content rapidly increased from approximately 5% to over 90%. Subsequently, the Oxy-Hb content stabilized, remaining at a high level of 92%–95%. Throughout the reaction, the methemoglobin (Met-Hb) content remained at a low level (<1%), without a significant increase, indicating that hemoglobin did not undergo significant oxidative degradation. This demonstrates that hemoglobin molecules can rapidly bind with oxygen in the air, exhibiting high oxygenation efficiency. This characteristic gives it a significant advantage in applications such as external wound repair and oxygen supply to hypoxic tissues, validating its functional reliability as an oxygen-carrying active ingredient.

[0067] Test Example 2: Long-term stability study of the composition

[0068] The physicochemical properties and active ingredient content of the pharmaceutical compositions prepared in Examples 1-4 and Comparative Examples 1-4 were tested under different storage conditions.

[0069] Test conditions: temperature 6±2℃, relative humidity (RH) 60%±5%, time points are 0, 1, 3, 6, 12 months.

[0070] Test method: Hemoglobin content was determined by spectrophotometry. A standard series of hemoglobin solutions with known concentrations ranging from 5 to 100 μg / mL was prepared. 200 μL of the spray sample was accurately taken and diluted to 1 mL with pure water. The absorbance at 410 nm was measured using a UV-Vis spectrophotometer. The concentration was obtained by substituting the values ​​into the curve, and the content retention rate was calculated (with an initial value of 100%).

[0071] The test results are shown in Table 1:

[0072] Table 1. Results of composition stability tests

[0073]

[0074]

[0075] As shown in Table 2, the pharmaceutical composition provided by this invention did not exhibit significant changes in the content of key functional components after 12 months of storage at room temperature and protected from light, indicating that the composition possesses good physicochemical stability. Comparative experiments revealed that the hemoglobin content retention rate was significantly reduced in the composition without the addition of lipoic acid and acetylcysteine. This demonstrates that the composite spray of this invention possesses excellent long-term storage stability and component activity retention capabilities, making it suitable for industrial production and clinical applications.

[0076] Test Case 3: Skin Irritation Study

[0077] Thirty-six rabbits were randomly divided into eight experimental groups and one control group, with four rabbits in each group (two with normal skin and two with damaged skin). Twenty-four hours before the experiment, long hair along both sides of the spine on the rabbits' backs was trimmed with curved scissors. A depilatory agent was evenly applied to the area to be depilated, and after 5 minutes, the hair was gently removed with a glass rod. The depilatory agent and the removed hair were then washed away with a cotton ball soaked in warm water (approximately 50 cm on each side). 2 (No erythema, edema, or skin lesions were observed). A skin lesion model was established in both the experimental and control groups by making crisscross cuts with a sterile needle at the hair-removed area, ensuring the epidermis was punctured without bleeding. In the experimental group, the left side of the hair-removed area of ​​rabbits was sprayed with the sprays from Examples 1-4 and Comparative Examples 1-4, with the right side serving as a blank control. In the control group, the left side of the hair-removed area of ​​rabbits was sprayed with 0.9% sodium chloride injection, with the right side serving as a blank control. Skin irritation reactions were observed and recorded at 1, 24, and 72 hours after medication.

[0078] Irritation assessment: Observe the degree of erythema (including eschar) and edema. ① Erythema reaction: No erythema is 0 points; barely visible erythema is 1 point; moderate erythema is 2 points; severe erythema is 3 points; purplish-red erythema with eschar formation is 4 points; ② Edema reaction: No edema is 0 points; barely visible edema is 1 point; clearly defined raised skin is 2 points; edema raised to about 1 cm and expanding in area is 4 points.

[0079] Stimulation score = (total score of erythema reaction + total score of edema reaction) / number of animals in each group. Stimulation score < 0.5 is no stimulation; ~ 2.0 is mild stimulation; ~ 6 is moderate stimulation; > 6 is strong stimulation.

[0080] The results are shown in Table 2:

[0081] Table 2 Results of the skin irritation test of hemoglobin spray on rabbits

[0082]

[0083]

[0084] As shown in Table 1, the combination of lipoic acid and acetylcysteine ​​in Examples 1-4 of this invention significantly reduced the skin irritation of the spray, with irritation scores all below 0.5 and no obvious adverse reactions such as erythema or peeling observed. In contrast, the comparative samples without lipoic acid and acetylcysteine, or using components without modified hemoglobin, showed significantly higher irritation scores, with some samples exhibiting erythema, peeling, and other irritant symptoms. The results indicate that the addition of lipoic acid and acetylcysteine ​​to the spray has synergistic antioxidant, membrane structure stabilizing, and inflammatory response-inhibiting effects, thereby significantly improving skin irritation and enhancing its safety in wound repair and topical medicine applications.

[0085] Test Example 4: Oxygen-carrying capacity analysis of hemoglobin spray

[0086] The pulse oximeter (GEM OPL) was used for measurement, and the optical calibration was performed using yellow and orange calibration plates respectively.

[0087] For oxygen-carrying sample testing, follow the GEM OPL operating instructions. The specific steps are as follows: Use a 1mL syringe to draw an appropriate amount of sample, insert the tip of the syringe into the test piece, keep the test piece at approximately 45° angle, and inject the sample evenly into the test piece, ensuring the sample reaches the vent of the test piece. Keep the syringe connected to the test piece, insert it into the GEM OPL slot, and select the appropriate option according to the instrument's display screen.

[0088] The results are shown in Table 3:

[0089] Table 3. GEM OPL Blood Gas Analysis Results

[0090]

[0091]

[0092] The results are shown in Table 3. Compared with Comparative Examples 1-4, Examples 1-4 generally showed a higher proportion of oxyhemoglobin, indicating that the combination of lipoic acid and acetylcysteine ​​can effectively maintain the oxygen-binding capacity of hemoglobin. Among them, the combination of synergistic antioxidant components in Examples 1 and 3 showed the best effect, and the presence of high concentrations of hemoglobin also resulted in higher total Hb values ​​and oxygenation rates. In Comparative Example 1, unmodified hemoglobin was used, and the methemoglobin content was the highest, indicating that its stability and functionality were the worst.

[0093] Test Example 5: Bacterial Endotoxin Detection

[0094] Endotoxin detection was performed using the horseshoe crab reagent microgel method, following the product instructions (sensitivity 0.125 EU / mL, Fuzhou Xinbei Biochemical Industry Co., Ltd.). The specific steps are as follows:

[0095] First, an endotoxin standard solution with twice the sensitivity was prepared using water for endotoxin testing. Then, the sample was diluted with water for endotoxin testing, and a positive control was prepared. Next, the horseshoe crab reagent was dissolved, mixed well, and added to the test tubes: the positive control tube contained the endotoxin standard solution, the negative control tube contained the water for endotoxin testing, and the test tube contained the diluted sample. The tubes were then sealed and placed vertically in a 37°C constant temperature water bath for 1 hour. Result interpretation: The test tube was removed from the constant temperature water bath and slowly inverted 180°. If a gel formed inside the tube and did not deform or slip off the tube wall, the result was positive; if no gel formed, or if the formed gel was weak, deformed, or slipped off the tube wall, the result was negative. The results are shown in Table 4.

[0096] Table 4. Endotoxin detection of wound healing sprays.

[0097]

[0098]

[0099] Table 4 shows that, based on the bacterial endotoxin test results, none of the spray products in the embodiments and comparative examples of this invention formed gel under the Limulus amebocyte lysate (LAL) microgel method (sensitivity 0.125 EU / mL), and were therefore deemed negative. This indicates that the endotoxin content in the products is low, meeting the pharmacopoeia standard for injectable drugs (less than 0.5 EU / mL), and is suitable for high-safety scenarios such as topical application or transdermal absorption. Test Example 6: Hemoglobin Spray's Healing-Promoting Effect in a Mouse Full-Thickness Skin Wound Model

[0100] (1) Animal model establishment: BALB / c female mice aged 6-8 weeks were anesthetized, their backs were shaved, and the tissues were disinfected with 75% ethanol. Two symmetrical full-thickness skin defects (reaching the muscle layer) were created using a sterile 8mm round hole punch. Each mouse was randomly divided into two groups: the experimental group (sprayed with the spray prepared in Example 1) and the control group (sprayed with PBS solution, pH 7.4), with 6 mice in each group.

[0101] (2) Medication treatment: Spray the wound area once a day, about 100 μL each time, and allow it to air dry after spraying. Continue treatment until the wound is completely healed (about 10-14 days).

[0102] (3) Take photos every two days to record the wound healing status, use ImageJ software to measure the wound area and calculate the healing rate.

[0103] (4) The results are shown in Table 5:

[0104] Table 5. Efficacy of hemoglobin spray on skin wound healing in mice.

[0105] Test Indicators Control Group (PBS) Example 1 Day 3 Residual Wound Area (%) 85.6±4.2 58.3±2.9** Day 7 Residual Wound Area (%) 46.7±5.0 18.2±3.1** Complete Healing Time (days) 13.8±1.1 8.6±0.7** surface

[0106] Note: All data are expressed as mean ± standard deviation (Mean ± SD), and statistical analysis was performed using a two-tailed t-test.

[0107] The results are shown in Table 5. The healing time of mouse wounds after treatment with the spray prepared in Example 1 of this application was significantly shortened, indicating that the pharmaceutical composition of the present invention can significantly improve the healing effect of mouse wounds.

[0108] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A pharmaceutical composition for promoting wound healing, characterized in that, The composition comprises, by weight, the following components: 5-10 parts hemoglobin molecules, 3-5 parts lipoic acid, 0.5-1 parts acetylcysteine, and 60 parts solvent; the hemoglobin molecule includes at least one cysteine ​​moiety and at least one histidine moiety, wherein the cysteine ​​moiety includes an acetyl group or an ethyl maleic group, and the histidine moiety includes a benzimidazole derivative group; the mass ratio of the hemoglobin molecule to the lipoic acid is (1-2):1; the solvent is physiological saline; the preparation method of the pharmaceutical composition includes the following steps: (1) Solution preparation: the hemoglobin molecule is added to physiological saline, and stirred on a magnetic stirrer at 300-500 rpm. (1) Stir at rpm to dissolve, and control the temperature at 4~8℃ to prevent protein denaturation to obtain a solution; (2) Add lipoic acid and acetylcysteine ​​to the solution in sequence, and continue stirring until all components are completely dissolved to obtain a mixture; (3) Add the spray matrix to the mixture, continue stirring until uniform, and then add physiological saline. Use phosphate buffer to control the pH in the range of 6.8~7.4; (4) Perform sterilization filtration on the mixture finally obtained in step (3) to obtain the drug composition.

2. A formulation, characterized in that, The formulation comprises the pharmaceutical composition of claim 1.

3. The formulation according to claim 2, characterized in that, The formulation is a spray.

4. The formulation according to claim 3, characterized in that, The spray also includes 5 to 20 parts of spray matrix, which is selected from one or more of film-forming agents, propellants, and humectants.

5. The formulation according to claim 4, characterized in that, The film-forming agent is selected from any one or more of polyvinylpyrrolidone, hydroxypropyl methylcellulose, sodium carboxymethyl cellulose, polyvinyl alcohol, chitosan, gelatin, carbomer, and hydroxypropyl cellulose.

6. The method for preparing the pharmaceutical composition according to claim 1, characterized in that, The steps include: (1) Solution preparation: Add hemoglobin molecules to physiological saline and stir at 300-500 rpm on a magnetic stirrer to dissolve them. The temperature is controlled at 4-8℃ to prevent protein denaturation, and a solution is obtained. (2) Add lipoic acid and acetylcysteine ​​to the solution in sequence, and stir continuously until all components are completely dissolved to obtain a mixture; (3) Add the spray matrix to the mixture, stir evenly, and then add physiological saline. Use phosphate buffer to control the pH in the range of 6.8 to 7.4; (4) Perform sterilization filtration on the mixture finally obtained in step (3) to obtain the drug composition.

7. The use of the pharmaceutical composition of claim 1 in the preparation of a medicament for promoting wound healing and repair.

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