Pharmaceutical composition for treating diabetic foot and preparation method thereof

Abstract

The invention provides a pharmaceutical composition for treating diabetic foot. The pharmaceutical composition comprises a traditional Chinese medicine active component, a growth factor, an antibacterial and antioxidant component, a microenvironment regulator and other auxiliary materials. The traditional Chinese medicine active components comprise 5-10 parts of a radix salviae miltiorrhizae extract, 3-8 parts of astragalus polysaccharide, 2-5 parts of dragon's blood and 1-3 parts of radix stemonae powder; the antibacterial and antioxidant components comprise 2 to 6 parts of chitosan, 0.1 to 0.5 part of nano-silver particles and 0.5 to 2 parts of vitamin E; 0.01 to 0.1 part of a growth factor; the microenvironment conditioning agent is prepared from hyaluronic acid and lactic acid according to the mass ratio of (0.1 to 0.5) to (0.05 to 0.3); the other auxiliary materials comprise 30 to 50 parts of chitosan composite hydrogel and 5 to 10 parts of glycerol. According to the invention, the traditional Chinese medicine active components are combined with the drug-loaded hydrogel to form the pharmaceutical composition with antibacterial, antioxidant and tissue regeneration promotion functions, and the pharmaceutical composition can be used for treating diabetic foot and has a good clinical application prospect.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical compositions, and more specifically to a pharmaceutical composition for treating diabetic foot and a method for preparing the same. Background Technology

[0002] Diabetic foot is a common complication of diabetes, mainly manifested as foot ulcers, infections, and deep tissue damage. In severe cases, it can lead to amputation, causing immense physical and psychological suffering for patients. The pathogenesis of diabetic foot is complex, involving multiple aspects such as neuropathy, vascular disease, infection, and impaired wound healing. Currently, treatment methods for diabetic foot mainly include controlling blood sugar, fighting infection, improving microcirculation, and promoting wound healing.

[0003] In the treatment of diabetic foot with traditional Chinese medicine, various herbal compositions have been developed and applied. For example, CN104367631A discloses a herbal composition containing tortoise shell for treating diabetic foot. This composition consists of Salvia miltiorrhiza, Gleditsia sinensis thorns, Astragalus membranaceus, and tortoise shell, exhibiting synergistic effects. It is used to treat diabetic foot with a short treatment course, good efficacy, and no side effects on patients. CN110115743A discloses a herbal composition for treating diabetic foot, containing raw Astragalus membranaceus, Scrophularia ningpoensis, raw Panax ginseng, Ophiopogon japonicus, Hirudo medicinalis, Fritillaria cirrhosa, Dioscorea opposita, and Salvia miltiorrhiza. It can invigorate qi and nourish yin, promote blood circulation and remove blood stasis, resolve phlegm and unblock collaterals, promote microcirculation, and promote the secretion of vascular endothelial growth factor.

[0004] In addition, CN103446307B discloses a traditional Chinese medicine composition for treating diabetic foot, including honeysuckle, dandelion, astragalus, phellodendron, atractylodes, angelica, salvia miltiorrhiza, safflower, geranium, clematis, chicken blood vine, and licorice. These traditional Chinese medicine components can be used to treat diabetic foot. CN111358883A proposes a pharmaceutical composition for treating diabetic foot, including nano-silver, astragalus, dragon's blood, donkey-hide gelatin, and borneol. This topical medicine can significantly improve blood circulation in the wound, with significant effects in draining pus and promoting tissue regeneration, achieving an efficacy rate of 99% and effectively reducing the risk of amputation. CN108210693A discloses a traditional Chinese medicine composition for diabetic foot, including angelica dahurica, angelica pubescens, cinnamon twig, and other traditional Chinese medicines, which have the effects of relieving exterior syndromes, clearing heat and detoxifying, dispelling wind, removing dampness, regulating qi, promoting blood circulation and removing blood stasis, and replenishing qi and blood.

[0005] However, current technologies still have some shortcomings in treating diabetic foot. First, existing Western medicine preparations, such as antibiotics and growth factors, typically target only a single aspect of diabetic foot treatment, such as anti-infection or promoting healing, lacking the ability to comprehensively improve the wound microenvironment. Second, while traditional Chinese medicine compound formulas have multi-target effects, their complex components, low absorption rates, and lack of modern formulation technology support make it difficult to achieve optimal efficacy. Third, long-term use of antibiotics can easily lead to bacterial resistance, while hormonal drugs may increase the risk of infection and worsen the condition. Finally, existing topical dressings, such as silver ion dressings, while possessing some antibacterial effects, lack the ability to regulate the entire wound process from the inflammatory phase to the remodeling phase, and cannot effectively promote the regeneration of new tissue.

[0006] Therefore, there is an urgent need to develop a topical compound that can integrate the synergistic effects of antibacterial, anti-inflammatory, angiogenesis-promoting, and tissue repair functions, while improving the bioavailability and stability of active ingredients, in order to meet the clinical needs of diabetic foot treatment. Summary of the Invention

[0007] In order to address the problems of insufficient single-function formulations, limitations of traditional Chinese medicine formulations, drug resistance and side effects, and low wound repair efficiency in existing technologies, and to achieve synergistic effects of multiple targets, improve wound healing rate and reduce scar formation, this invention provides a multi-effect composite composition for treating diabetic foot.

[0008] The objective of this invention is achieved through the following technical solution: a pharmaceutical composition for treating diabetic foot, comprising the following raw materials: active components of traditional Chinese medicine, growth factors, antibacterial and antioxidant components, microenvironment regulators, and other excipients.

[0009] Preferably, the pharmaceutical composition comprises the following raw materials in parts by weight: Active components of traditional Chinese medicine: 5-10 parts of Salvia miltiorrhiza extract, 3-8 parts of Astragalus membranaceus polysaccharide, 2-5 parts of dragon's blood, and 1-3 parts of Stemona japonica powder; Antibacterial and antioxidant components: 2-6 parts chitosan, 0.1-0.5 parts nano silver particles, 0.5-2 parts vitamin E; Growth factor 0.01-0.1 parts, microenvironment regulator 0.5-8 parts, other excipients 5-60 parts.

[0010] Preferably, the microenvironment regulator is composed of hyaluronic acid and lactic acid in a mass ratio of 0.1-0.5:0.05-0.3.

[0011] Preferably, the other excipients are chitosan composite hydrogel and glycerin.

[0012] Preferably, the other excipients are 30-50 parts of chitosan composite hydrogel and 5-10 parts of glycerol.

[0013] Preferably, the growth factor is at least one of recombinant human epidermal growth factor, venous endothelial growth factor, basic fibroblast growth factor bFGF-21, platelet-derived growth factor PDGF-AA, and platelet-derived growth factor PDGF-BB.

[0014] Preferably, the tanshinone extract is prepared by the following method: Remove impurities, moldy and insect-infested parts from the danshen, rinse quickly with running water, dry at a low temperature of 40℃ after washing, and pulverize through a 10-20 mesh sieve to obtain danshen powder with a moisture content ≤10%; The processed Salvia miltiorrhiza powder was mixed with 50-90% ethanol at a material-to-liquid ratio of 1:8-15 and refluxed for extraction. The extraction temperature was controlled at 78-82℃, and the extraction time was 1h, 1.5h, 2h, and 2.5h for a total of four reflux extractions. The filtrates from the four reflux extractions were combined, filtered through a 400-mesh sieve, the ethanol was recovered, and the mixture was concentrated to a relative density of 1.15-1.20 to obtain the Salvia miltiorrhiza extract.

[0015] Preferably, the astragalus polysaccharide is prepared by the following method: Remove impurities, moldy and insect-infested parts from the Astragalus membranaceus, rinse quickly with running water, dry at a low temperature of 40-50℃ after washing, and pulverize through a 40-80 mesh sieve to obtain Astragalus membranaceus powder with a moisture content ≤12%; The processed Astragalus powder was mixed with 30-50% ethanol at a material-to-liquid ratio of 1:8-12 and refluxed for extraction. The extraction temperature was controlled at 75-80℃, and the extraction time was 1h, 1.5h, 2h, and 2.5h for a total of four reflux extractions. The filtrates from the four reflux extractions were combined, filtered through a 200-mesh sieve, the ethanol was recovered, and the mixture was concentrated to 1 / 5 of its original volume. The precipitate was collected by centrifugation to obtain Astragalus polysaccharide.

[0016] The present invention also provides a method for preparing a pharmaceutical composition for treating diabetic foot, comprising the following raw materials in parts by weight: S1. According to the weight parts, mix and concentrate the salvia miltiorrhiza extract and astragalus polysaccharide, then mix with the blood draconis and stemona japonica powder to obtain the active components of traditional Chinese medicine for later use. S2. Chitosan is dissolved in a 1% acetic acid solution, then mixed with hyaluronic acid and lactic acid to crosslink and obtain a hydrogel. At the same time, it is mixed with the chitosan composite hydrogel, and growth factors and vitamin E are added to load and obtain a nanocarrier for later use. S3. According to the weight parts, the nano-silver particles are embedded into the hydrogel network through electrostatic interaction, and chitosan is further coated to enhance stability. S4. According to the weight proportions, add glycerin to adjust the viscosity and classify it as a gel pharmaceutical composition or a spray pharmaceutical composition.

[0017] The beneficial effects of this invention are as follows: 1. Synergistic Multi-Target Effect: The pharmaceutical composition of this invention achieves comprehensive treatment of diabetic foot wounds through the synergistic effects of active components of traditional Chinese medicine, growth factors, antibacterial and antioxidant ingredients, and microenvironment modifiers. Specifically, chitosan and nano-silver can disrupt bacterial membrane structures, effectively inhibiting pathogens such as Staphylococcus aureus and Escherichia coli; vitamin E scavenge free radicals and reduce oxidative stress; tanshinone extract activates the VEGF pathway and improves local microcirculation; astragalus polysaccharide enhances immune cell activity; recombinant human epidermal growth factor promotes epidermal cell proliferation; dragon's blood and stemona extract accelerate granulation tissue formation and reduce scarring; lactic acid and hyaluronic acid construct a weakly acidic environment (pH 5.5–6.5), inhibiting bacterial growth and promoting wound healing.

[0018] 2. Experimental verification shows significant effects: In vitro antibacterial experiments show that the drug composition of the present invention has an inhibition zone diameter of 18 mm against Staphylococcus aureus (plate diffusion method); in animal model verification, the wound healing rate of the treatment group reached 92%, which was significantly higher than that of the control group (45%), and the newly formed collagen was neatly arranged, and the scar area was reduced by 60% to 78%; at the same time, the composition has excellent biocompatibility (cell survival rate >95%).

[0019] 3. Outstanding Innovation: This invention is the first to combine the active ingredients of traditional Chinese medicine with modern nanomaterials to achieve full-process regulation of antibacterial, anti-inflammatory, angiogenesis-promoting, and tissue repair effects; through an intelligent microenvironment response mechanism, it dynamically adjusts pH to enhance the antibacterial effect while promoting the release of growth factors and reversing osteonecrosis; the combination of nano-silver and chitosan reduces the toxicity of individual components, achieving a low-toxicity and high-efficiency therapeutic effect.

[0020] Compared with the prior art, the pharmaceutical composition of the present invention overcomes the problems of insufficient single-function formulations, limitations of traditional Chinese medicine formulations, drug resistance and side effects, and low wound repair efficiency, providing a novel multi-effect compound composition for the treatment of diabetic foot. Detailed Implementation

[0021] To facilitate understanding by those skilled in the art, the present invention will be further described below with reference to embodiments. The content mentioned in the embodiments is not intended to limit the present invention.

[0022] Example 1 This embodiment provides a pharmaceutical composition for treating diabetic foot, the pharmaceutical composition comprising active components of traditional Chinese medicine, growth factors, antibacterial and antioxidant components, microenvironment regulators and other excipients.

[0023] Specifically, the pharmaceutical composition comprises the following raw materials in parts by weight: Active components of traditional Chinese medicine: 8 parts of Salvia miltiorrhiza extract, 5 parts of Astragalus membranaceus polysaccharide, 3 parts of dragon's blood, and 2 parts of Stemona japonica powder; Antibacterial and antioxidant components: 4 parts chitosan, 0.3 parts nano silver particles, and 1 part vitamin E; Growth factor 0.05 parts; 3 parts of microenvironment conditioner; 45 portions of other auxiliary materials.

[0024] The microenvironment regulator consists of hyaluronic acid and lactic acid in a mass ratio of 0.3:0.2. Hyaluronic acid provides a good moisturizing environment and promotes wound healing, while lactic acid regulates the local pH value, creating a microenvironment conducive to tissue regeneration. The combination of hyaluronic acid and lactic acid can be adjusted within a mass ratio range of 0.1-0.5:0.05-0.3, for example, ratios such as 0.1:0.05, 0.2:0.1, or 0.5:0.3, but a ratio of 0.3:0.2 shows the best synergistic effect in practical applications.

[0025] Other excipients include 40 parts chitosan composite hydrogel and 5 parts glycerin. The chitosan composite hydrogel has good biocompatibility and water absorption, which can maintain a moist environment in the wound and promote tissue regeneration; glycerin acts as a humectant to prevent the drug composition from drying out and improve its user comfort.

[0026] The growth factors used in this embodiment are a mixture of recombinant human epidermal growth factor and venous endothelial growth factor. Growth factors can promote cell proliferation and differentiation during wound healing, accelerating tissue repair. In a preferred embodiment, basic fibroblast growth factor bFGF21, platelet-derived growth factor PDGFAA, or platelet-derived growth factor PDGFBB can also be selected as growth factor components, or a combination thereof can be used.

[0027] The tanshinone extract in this embodiment was prepared by the following method: First, remove impurities, moldy and insect-infested parts from the danshen, rinse it quickly with running water, dry it at a low temperature of 40℃ after washing, and then pulverize it and pass it through a 15-mesh sieve to obtain danshen powder with a moisture content of about 8%. Next, the processed Salvia miltiorrhiza powder was mixed with 70% ethanol at a material-to-liquid ratio of 1:10 and refluxed for extraction. The extraction temperature was controlled at 80℃. The first extraction time was 1 hour, the second extraction time was 1.5 hours, the third extraction time was 2 hours, and the fourth extraction time was 2.5 hours. A total of four reflux extractions were performed. The filtrates from the four reflux extractions were combined, filtered through a 400-mesh sieve, and then the ethanol was recovered and concentrated to a relative density of 1.18 to obtain the final Danshen extract.

[0028] Astragalus polysaccharides are prepared using the following methods: First, remove impurities, moldy and insect-infested parts from the astragalus root, rinse it quickly with running water, dry it at a low temperature of 45℃ after washing, and then pulverize it and pass it through a 60-mesh sieve to obtain astragalus powder with a moisture content of about 10%. Next, the processed Astragalus powder was mixed with 40% ethanol at a material-to-liquid ratio of 1:10 and refluxed for extraction. The extraction temperature was controlled at 78℃. The first extraction time was 1 hour, the second extraction time was 1.5 hours, the third extraction time was 2 hours, and the fourth extraction time was 2.5 hours. A total of four reflux extractions were performed. The filtrates from the four reflux extractions were combined, filtered through a 200-mesh sieve, and then the ethanol was recovered. The mixture was concentrated to 1 / 5 of its original volume, centrifuged, and the precipitate was collected to obtain Astragalus polysaccharide.

[0029] The preparation process of this pharmaceutical composition is as follows: First, the extract of Salvia miltiorrhiza, polysaccharide of Astragalus membranaceus, blood stasis and powder of Stemona japonica are mixed evenly to obtain a mixture of active components of traditional Chinese medicine. Then chitosan, silver nanoparticles and vitamin E are mixed to obtain a mixture of antibacterial and antioxidant components; Next, hyaluronic acid and lactic acid were mixed at a mass ratio of 0.3:0.2 to obtain a microenvironment regulator; The above three mixtures are mixed with growth factors, and then chitosan composite hydrogel and glycerin are added. After thorough mixing, a pharmaceutical composition for treating diabetic foot is obtained.

[0030] The components in this drug composition work synergistically to treat diabetic foot: the active ingredients of the traditional Chinese medicine, including danshen extract, have the effect of promoting blood circulation and removing blood stasis; astragalus polysaccharide can enhance immunity; dragon's blood has the effects of stopping bleeding, reducing swelling, and promoting tissue regeneration; and stemona powder has antibacterial effects. The antibacterial and antioxidant components, including chitosan and nano-silver particles, can inhibit bacterial growth, and vitamin E has antioxidant effects. Growth factors promote wound healing; microenvironment regulators regulate the wound microenvironment and create favorable conditions for tissue regeneration; and other excipients provide a good carrier to ensure that the drug composition can be effectively applied to the wound surface.

[0031] Example 2 A pharmaceutical composition for treating diabetic foot comprises the following raw materials in parts by weight: Active components of traditional Chinese medicine: 5 parts of Salvia miltiorrhiza extract, 3 parts of Astragalus membranaceus polysaccharide, 2 parts of dragon's blood, and 1 part of Stemona japonica powder; Antibacterial and antioxidant components: 2 parts chitosan, 0.1 parts nano silver particles, and 0.5 parts vitamin E; 0.01 parts growth factor, 0.5 parts microenvironment regulator, and 5 parts other excipients.

[0032] The microenvironment regulator is composed of hyaluronic acid and lactic acid in a mass ratio of 0.1:0.05.

[0033] The other excipients are chitosan composite hydrogel and glycerin.

[0034] The other excipients are 30 parts chitosan composite hydrogel and 5 parts glycerin.

[0035] The growth factor is recombinant human epidermal growth factor.

[0036] The tanshinone extract was prepared by the following method: Remove impurities, moldy and insect-infested parts from the danshen, rinse quickly with running water, dry at a low temperature of 40℃ after washing, and pulverize through a 10-20 mesh sieve to obtain danshen powder with a moisture content ≤10%; The processed Salvia miltiorrhiza powder was mixed with 50% ethanol at a material-to-liquid ratio of 1:8 and refluxed for extraction. The extraction temperature was controlled at 78℃, and the extraction time was 1h, 1.5h, 2h, and 2.5h, for a total of four reflux extractions. The filtrates from the four reflux extractions were combined, filtered through a 400-mesh sieve, the ethanol was recovered, and the mixture was concentrated to a relative density of 1.15 to obtain the Salvia miltiorrhiza extract.

[0037] The Astragalus polysaccharide was prepared by the following method: Remove impurities, moldy and insect-infested parts from the Astragalus membranaceus, rinse quickly with running water, dry at a low temperature of 40℃ after washing, and pulverize through a 40-mesh sieve to obtain Astragalus membranaceus powder with a moisture content ≤12%; The processed Astragalus powder was mixed with 30% ethanol at a material-to-liquid ratio of 1:8 and refluxed for extraction. The extraction temperature was controlled at 75℃, and the extraction time was 1h, 1.5h, 2h, and 2.5h, for a total of four reflux extractions. The filtrates from the four reflux extractions were combined, filtered through a 200-mesh sieve, the ethanol was recovered, and the mixture was concentrated to 1 / 5 of its original volume. The precipitate was collected by centrifugation to obtain Astragalus polysaccharide.

[0038] Example 3 A pharmaceutical composition for treating diabetic foot comprises the following raw materials in parts by weight: Active components of traditional Chinese medicine: 10 parts of Salvia miltiorrhiza extract, 8 parts of Astragalus membranaceus polysaccharide, 5 parts of dragon's blood, and 3 parts of Stemona japonica powder; Antibacterial and antioxidant components: 6 parts chitosan, 0.5 parts nano silver particles, and 2 parts vitamin E; Growth factor 0.1 parts, microenvironment regulator 8 parts, other excipients 60 parts.

[0039] The microenvironment regulator is composed of hyaluronic acid and lactic acid in a mass ratio of 0.5:0.3.

[0040] The other excipients are chitosan composite hydrogel and glycerin.

[0041] The other excipients are 50 parts chitosan composite hydrogel and 10 parts glycerin.

[0042] The growth factor is recombinant human epidermal growth factor.

[0043] The tanshinone extract was prepared by the following method: Remove impurities, moldy and insect-infested parts from the Salvia miltiorrhiza, rinse quickly with running water, dry at a low temperature of 40℃ after washing, pulverize and pass through a 20-mesh sieve to obtain Salvia miltiorrhiza powder with a moisture content ≤10%; The processed Salvia miltiorrhiza powder was mixed with 90% ethanol at a material-to-liquid ratio of 1:15 and refluxed for extraction. The extraction temperature was controlled at 82℃, and the extraction time was 1h, 1.5h, 2h, and 2.5h, for a total of four reflux extractions. The filtrates from the four reflux extractions were combined, filtered through a 400-mesh sieve, the ethanol was recovered, and the mixture was concentrated to a relative density of 1.20 to obtain the Salvia miltiorrhiza extract.

[0044] The Astragalus polysaccharide was prepared by the following method: Remove impurities, moldy and insect-infested parts from the Astragalus membranaceus, rinse quickly with running water, dry at a low temperature of 50℃ after washing, and pulverize through an 80-mesh sieve to obtain Astragalus membranaceus powder with a moisture content ≤12%; The processed Astragalus powder was mixed with 50% ethanol at a material-to-liquid ratio of 1:12 and refluxed for extraction. The extraction temperature was controlled at 80℃, and the extraction time was 1h, 1.5h, 2h, and 2.5h, for a total of four reflux extractions. The filtrates from the four reflux extractions were combined, filtered through a 200-mesh sieve, the ethanol was recovered, and the mixture was concentrated to 1 / 5 of its original volume. The precipitate was collected by centrifugation to obtain Astragalus polysaccharide.

[0045] Example 4 This embodiment provides a method for preparing a pharmaceutical composition for treating diabetic foot, comprising the following steps: S1: According to the weight parts, the extract of Salvia miltiorrhiza and the polysaccharide of Astragalus membranaceus are mixed and concentrated, and then mixed with the powders of blood stasis and Stemona japonica to obtain the active components of traditional Chinese medicine for later use.

[0046] Specifically, the danshen extract is prepared by the following method: Danshen is cleaned by removing impurities, mold, and insect-infested parts, quickly rinsed with running water, dried at 40℃, and pulverized through a 15-mesh sieve to obtain danshen powder with a moisture content of 8%. The treated danshen powder is then mixed with 70% ethanol at a material-to-liquid ratio of 1:10 and refluxed for extraction. The extraction temperature is controlled at 80℃, and the extraction times are 1h, 1.5h, 2h, and 2.5h, for a total of four reflux extractions. The filtrates from the four reflux extractions are combined, filtered through a 400-mesh sieve, the ethanol is recovered, and the mixture is concentrated to a relative density of 1.18 to obtain the danshen extract.

[0047] Astragalus polysaccharides were prepared by the following method: Impurities, moldy, and insect-infested parts of Astragalus were removed, and the powder was quickly rinsed with running water. After washing, it was dried at a low temperature of 45℃, pulverized, and passed through a 60-mesh sieve to obtain Astragalus powder with a moisture content of 10%. The treated Astragalus powder was mixed with 40% ethanol at a material-to-liquid ratio of 1:10 and refluxed for extraction. The extraction temperature was controlled at 78℃, and the extraction times were 1h, 1.5h, 2h, and 2.5h, for a total of four reflux extractions. The filtrates from the four reflux extractions were combined, filtered through a 200-mesh sieve, and the ethanol was recovered. The filtrate was concentrated to 1 / 5 of its original volume, centrifuged, and the precipitate was collected to obtain Astragalus polysaccharides.

[0048] S2: Chitosan is dissolved in a 1% acetic acid solution, then mixed with hyaluronic acid and lactic acid to crosslink and obtain a hydrogel. At the same time, it is mixed with the chitosan composite hydrogel, and growth factors and vitamin E are added to load and obtain a nanocarrier for later use.

[0049] In this step, the amount of chitosan composite hydrogel used is 40 parts. The growth factor is selected from at least one of recombinant human epidermal growth factor, venous endothelial growth factor, basic fibroblast growth factor bFGF21, platelet-derived growth factor PDGFAA, and platelet-derived growth factor PDGFBB. In a preferred embodiment, recombinant human epidermal growth factor and venous endothelial growth factor are used simultaneously in a mass ratio of 2:1.

[0050] S3: According to the weight proportions, the nano-silver particles are embedded into the hydrogel network through electrostatic interaction, and chitosan is further coated to enhance stability.

[0051] Specifically, a suspension of silver nanoparticles was dropwise added to the nanocarrier obtained in S2, and stirred at 25°C for 2 hours to allow the silver nanoparticles to embed into the hydrogel network through electrostatic interaction. Subsequently, a chitosan solution (3% concentration) was added for coating, and after stirring for 1 hour, the mixture was allowed to stand overnight to allow the chitosan to fully coat the surface of the nanocarrier, thereby enhancing the stability of the entire system.

[0052] S4: Add glycerin according to the weight to adjust the viscosity, and classify it as a gel pharmaceutical composition or a spray pharmaceutical composition.

[0053] In this step, the amount of glycerin used is 8 parts. The viscosity of the final product can be adjusted according to different clinical needs. For deep wounds, a gel-like drug composition with higher viscosity is prepared, which can remain on the wound for a longer time; for large superficial wounds, a spray-like drug composition with lower viscosity is prepared, which is convenient for uniform coverage of the wound surface.

[0054] The efficacy of the prepared pharmaceutical composition can be verified by the following methods: Rats with diabetic foot were randomly divided into a control group, a gel group, and a spray group, with 10 rats in each group. The control group received conventional treatment, while the gel group and spray group received the gel and spray formulations prepared in this embodiment, respectively, twice daily for 14 consecutive days. The treatment effect was evaluated by observing wound healing speed, inflammatory markers, and histological examination. The results showed that the experimental group treated with the formulation prepared in this embodiment exhibited significantly faster wound healing, significantly lower inflammatory markers, and increased angiogenesis at the wound site, indicating that the formulation prepared in this embodiment has a significant therapeutic effect on diabetic foot.

[0055] Finally, it should be noted that the above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art can still modify the technical solutions described in the foregoing embodiments or make equivalent substitutions for some of the technical features. 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 treating diabetic foot, characterized in that: It includes the following raw materials: active components of traditional Chinese medicine, growth factors, antibacterial and antioxidant components, microenvironment regulators, and other excipients.

2. The pharmaceutical composition for treating diabetic foot according to claim 1, characterized in that: The pharmaceutical composition comprises the following raw materials in parts by weight: Active components of traditional Chinese medicine: 5-10 parts of Salvia miltiorrhiza extract, 3-8 parts of Astragalus membranaceus polysaccharide, 2-5 parts of dragon's blood, and 1-3 parts of Stemona japonica powder; Antibacterial and antioxidant components: 2-6 parts chitosan, 0.1-0.5 parts nano silver particles, 0.5-2 parts vitamin E; Growth factor 0.01-0.1 parts, microenvironment regulator 0.5-8 parts, other excipients 5-60 parts.

3. A pharmaceutical composition for treating diabetic foot according to claim 2, characterized in that: The microenvironment regulator is composed of hyaluronic acid and lactic acid in a mass ratio of 0.1-0.5:0.05-0.

3.

4. A pharmaceutical composition for treating diabetic foot according to claim 2, characterized in that: The other excipients are chitosan composite hydrogel and glycerin.

5. A pharmaceutical composition for treating diabetic foot according to claim 4, characterized in that: The other excipients are 30-50 parts of chitosan composite hydrogel and 5-10 parts of glycerol.

6. A pharmaceutical composition for treating diabetic foot according to claim 2, characterized in that: The growth factor is at least one of recombinant human epidermal growth factor, venous endothelial growth factor, basic fibroblast growth factor bFGF 21, platelet-derived growth factor PDGF AA, and platelet-derived growth factor PDGF BB.

7. A pharmaceutical composition for treating diabetic foot according to claim 2, characterized in that: The tanshinone extract was prepared by the following method: Remove impurities, moldy and insect-infested parts from the danshen, rinse quickly with running water, dry at a low temperature of 40℃ after washing, and pulverize through a 10-20 mesh sieve to obtain danshen powder with a moisture content ≤10%; The processed Salvia miltiorrhiza powder was mixed with 50-90% ethanol at a material-to-liquid ratio of 1:8-15 and refluxed for extraction. The extraction temperature was controlled at 78-82℃, and the extraction time was 1h, 1.5h, 2h, and 2.5h for a total of four reflux extractions. The filtrates from the four reflux extractions were combined, filtered through a 400-mesh sieve, the ethanol was recovered, and the mixture was concentrated to a relative density of 1.15-1.20 to obtain the Salvia miltiorrhiza extract.

8. A pharmaceutical composition for treating diabetic foot according to claim 1, characterized in that: The Astragalus polysaccharide was prepared by the following method: Remove impurities, moldy and insect-infested parts from the Astragalus membranaceus, rinse quickly with running water, dry at a low temperature of 40-50℃ after washing, and pulverize through a 40-80 mesh sieve to obtain Astragalus membranaceus powder with a moisture content ≤12%; The processed Astragalus powder was mixed with 30-50% ethanol at a material-to-liquid ratio of 1:8-12 and refluxed for extraction. The extraction temperature was controlled at 75-80℃, and the extraction time was 1h, 1.5h, 2h, and 2.5h for a total of four reflux extractions. The filtrates from the four reflux extractions were combined, filtered through a 200-mesh sieve, the ethanol was recovered, and the mixture was concentrated to 1 / 5 of its original volume. The precipitate was collected by centrifugation to obtain Astragalus polysaccharide.

9. A method for preparing a pharmaceutical composition for treating diabetic foot as described in any one of claims 4-8, characterized in that: The ingredients include the following parts by weight: S1. According to the weight parts, mix and concentrate the salvia miltiorrhiza extract and astragalus polysaccharide, then mix with the blood draconis and stemona japonica powder to obtain the active components of traditional Chinese medicine for later use. S2. Chitosan is dissolved in a 1% acetic acid solution, then mixed with hyaluronic acid and lactic acid to crosslink and obtain a hydrogel. At the same time, it is mixed with the chitosan composite hydrogel, and growth factors and vitamin E are added to load and obtain a nanocarrier for later use. S3. According to the weight parts, the nano-silver particles are embedded into the hydrogel network through electrostatic interaction, and chitosan is further coated to enhance stability. S4. According to the weight proportions, add glycerin to adjust the viscosity and classify it as a gel pharmaceutical composition or a spray pharmaceutical composition.