Traditional Chinese medicine compound loaded wound and ulcer paste for promoting chronic wound healing and preparation method thereof

Abstract

The invention relates to the technical field of biological medicines, and particularly discloses a chronic wound healing promoting traditional Chinese medicine compound loaded wound and ulcer paste, which comprises a hydrogel matrix and a traditional Chinese medicine compound, and the traditional Chinese medicine compound is prepared from the following raw materials in parts by weight: 5-15 parts of rheum officinale, 4-8 parts of bletilla striata, 15-25 parts of astragalus membranaceus, 5-15 parts of salvia miltiorrhiza, 1-5 parts of cinnamon and 0.5-1.5 parts of borneol. The wound and ulcer paste loaded with the traditional Chinese medicine compound for promoting chronic wound healing can continuously and stably act on a target organ, the wound is isolated from the outside to prevent infection, meanwhile, the drug effect can be better brought into play, and therefore the treatment effect of chronic wound healing is improved.

Description

Technical Field

[0001] This invention relates to the field of biopharmaceutical technology, specifically to a wound ointment containing a traditional Chinese medicine compound that promotes the healing of chronic wounds and its preparation method. Background Technology

[0002] Chronic wounds refer to difficult-to-heal wounds caused by various factors such as diabetic ulcers, pressure sores, and burns, which are hindered in the normal healing process. These wounds are often accompanied by bacterial or fungal infections, triggering a persistent inflammatory response. In severe cases, this can damage capillaries, form hematomas, and cause tissue necrosis, significantly impacting the healing speed and quality, and hindering skin tissue regeneration and functional reconstruction, resulting in long-term effects on the patient's appearance and quality of life. Traditional hydrogels used to promote chronic wound healing are mostly single-component products such as polylactic acid, whose biocompatibility and stability are limited under different physiological conditions. Traditional Chinese medicine formulas are prone to rapid efficacy decay due to oxidation or other factors. While oils and creams can adjust stability through a matrix, their components are usually relatively simple, making it difficult to optimize long-term effects. Existing research indicates that combining traditional Chinese medicine formulas with composite materials such as hydrogels can better meet the needs under various environmental conditions. The multi-target mechanism and stability of traditional Chinese medicine formulas, combined with the permeability, controlled release, and biocompatibility of hydrogels, make this novel biomedical material a promising candidate for application. Scholars have also conducted research on this topic. For example, Chinese patent application number 201911069521.1 mentions a traditional Chinese medicine compound hydrogel for treating skin wound healing, its preparation method, and its application. It consists of a traditional Chinese medicine composition and a matrix. The traditional Chinese medicine composition includes stir-fried Scutellaria baicalensis, Codonopsis pilosula, Angelica sinensis, stir-fried Atractylodes macrocephala, Paeonia lactiflora, Poria cocos, Citrus reticulata peel, processed Boswellia carterii, processed Commiphora myrrha, Bletilla striata, Lonicera japonica, Coptis chinensis, and Glycyrrhiza uralensis. Compared with simple hydrogels, it can better promote the healing of chronic wounds. Therefore, developing richer and more effective wound ointment products loaded with traditional Chinese medicine is of great practical significance. Summary of the Invention

[0003] The technical problem solved by this invention is to provide a wound ointment containing a traditional Chinese medicine compound that promotes the healing of chronic wounds and its preparation method, so as to obtain a wound ointment product with good biocompatibility, high stability, good safety and effective promotion of chronic wound healing.

[0004] The technical problem solved by this invention is achieved by the following technical solution: A wound ointment containing a traditional Chinese medicine compound to promote chronic wound healing includes a hydrogel matrix and a traditional Chinese medicine compound, wherein the traditional Chinese medicine compound is composed of the following raw materials in parts by weight: rhubarb 5-15 parts, Bletilla striata 4-8 parts, Astragalus membranaceus 15-25 parts, Salvia miltiorrhiza 5-15 parts, cinnamon 1-5 parts, and borneol 0.5-1.5 parts.

[0005] Furthermore, the concentration of the traditional Chinese medicine compound in the wound ointment is 25~75mg / g.

[0006] Furthermore, the traditional Chinese medicine compound is composed of the following raw materials in parts by weight: 10 parts rhubarb, 6 parts Bletilla striata, 20 parts Astragalus membranaceus, 10 parts Salvia miltiorrhiza, 3 parts cinnamon, and 1 part borneol.

[0007] Furthermore, the hydrogel matrix comprises 2.5~10 mg / g carbomer 940, 10~20 mg / g Bletilla striata polysaccharide, and the balance being water.

[0008] Furthermore, the hydrogel matrix comprises 5 mg / g carbomer 940, 20 mg / g Bletilla striata polysaccharide, and the remainder is water.

[0009] The method for preparing the wound ointment containing a traditional Chinese medicine compound that promotes chronic wound healing includes the following steps: 1) Weigh out rhubarb, Bletilla striata, Astragalus membranaceus, Salvia miltiorrhiza, cinnamon and borneol in proportion, extract with water and freeze dry to obtain freeze-dried powder of Chinese herbal compound extract, dissolve the freeze-dried powder in water to obtain Chinese herbal compound extract. 2) Mix carbomer 940, Bletilla striata polysaccharide and water in a certain proportion and let stand until completely dissolved. Stir evenly and let stand to obtain hydrogel matrix. 3) Mix the Chinese herbal compound extract with the hydrogel matrix until the matrix concentration is 5 mg / g carbomer 940 and 20 mg / g Bletilla striata polysaccharide and different concentrations of Chinese herbal compound extract, stir until completely dissolved, and then add triethanolamine to neutralize to obtain the wound ointment loaded with Chinese herbal compound.

[0010] Further, in step 1), during extraction, the mass ratio of the Chinese herbal raw materials composed of rhubarb, Bletilla striata, Astragalus membranaceus, Salvia miltiorrhiza, cinnamon, and borneol to water is 1:5~10, the extraction temperature is 75~85℃, the extraction time is 1h~2h, and the extraction is repeated 1~3 times. After combining the extracts, the extracts are concentrated and freeze-dried.

[0011] Furthermore, in step 2), the settling time is 10~14h.

[0012] Furthermore, in step 3), the stirring speed is 300–500 rpm.

[0013] Beneficial Effects: In this invention, Astragalus membranaceus is the principal ingredient, with a sweet and warm nature, specializing in tonifying Qi and raising Yang, strengthening Qi and consolidating the exterior. It is an essential medicine for chronic wounds that do not heal for a long time and for Qi and blood deficiency. Salvia miltiorrhiza is the assistant ingredient, with a bitter and slightly cold nature, mainly entering the blood level, functioning to activate blood circulation and remove blood stasis, improve local blood circulation, assist Astragalus membranaceus in promoting tissue regeneration, and also counteract the warm nature of Astragalus membranaceus. Rhubarb and Bletilla striata are the adjuvant ingredients. Rhubarb is bitter, cold, and descending, with the ability to clear heat and purge fire, cool blood and detoxify. In this formula, it is used to purge fire and detoxify, activate blood circulation and remove blood stasis, to clear residual heat and blood stasis in the wound. Bletilla striata is slightly cold, bitter and sweet, with the ability to astringe and stop bleeding, reduce swelling and promote tissue regeneration. Its texture is extremely sticky, which can seal the wound and promote healing, assisting the principal and assistant ingredients in harmonizing the cold and warm nature. Cinnamon and borneol are used together as guiding herbs. Cinnamon can dispel cold and relieve pain, warm and unblock the meridians; a small amount can invigorate qi and blood, and assist the warming and transporting effects of astragalus. Borneol is bitter, pungent, and slightly cold, clearing heat and relieving pain, and opening the orifices and refreshing the mind. The entire formula is meticulously formulated to address the core pathogenesis of chronic wounds characterized by deficiency of both qi and blood, and internal accumulation of blood stasis and toxins. Borneol, being cool in nature, assists in clearing heat and detoxifying, and has excellent effects in reducing swelling and relieving pain. The wound ointment containing traditional Chinese medicine compound described in this invention promotes the healing of chronic wounds. Through the creative combination of traditional Chinese medicine compound and specific hydrogel matrix, it can effectively invigorate qi and blood, remove necrotic tissue and promote tissue regeneration, thereby regulating qi and blood, improving the microenvironment and promoting healing. It is specifically designed for the core pathogenesis of chronic wounds, which is "qi deficiency as the root cause and blood stasis and phlegm obstruction as the symptoms". In this way, the invention can continuously and stably act on the target organ, isolate the wound from external contact to prevent infection, and better facilitate the efficacy of the medicine, thereby improving the therapeutic effect of chronic wound healing and filling the gaps in modern medicine in the dimensions of immune regulation and tissue regeneration of chronic wounds.

[0014] The method for preparing a wound ointment containing a traditional Chinese medicine compound that promotes chronic wound healing, as described in this invention, uses readily available raw materials, has a simple preparation process, and allows for easy control of key points. It produces a wound ointment product with better efficacy using a simpler raw material formula, making it suitable for large-scale processing and production, and has excellent application prospects. Attached Figure Description

[0015] Figure 1 The images are scanning electron microscope (SEM) images of the wound ointment products in Examples 1, 2, 3 and Comparative Example 1 of this invention.

[0016] Figure 2 These are digital photographs taken during the preparation process of the wound ointment product in an embodiment of the present invention.

[0017] Figure 3 This diagram illustrates the injectability of the wound ointment product in an embodiment of the present invention.

[0018] Figure 4 These are visual images showing the wound healing of the wound ointment products prepared in Examples 1-3, Control Example 1, Control Example 5, and Control Example 6 on the burn wound model rats.

[0019] Figure 5The images show the HE staining results of the wound tissue when the wound ointment products prepared in Examples 1-3, Control Example 1, Control Example 5, and Control Example 6 were applied to the wounds of rats with burn wounds.

[0020] Figure 6 The images show the Masson trichrome staining results of the wound tissue when the wound ointment products prepared in Examples 1-3, Control Example 1, Control Example 5, and Control Example 6 were applied to the wounds of rats with burn wounds.

[0021] Figure 7 These are intuitive images showing the wound healing of the wounds on a rat burn wound model, obtained from the wound ointment products prepared in Examples 2, 5, and 6.

[0022] Figure 8 The image shows the HE staining results of the wound tissue on day 9 when the wound ointment products prepared in Example 2, Control Example 5, and Control Example 6 were applied to the wounds of rats with burn wound models.

[0023] Figure 9 The frequency scan results are for the wound ointment products of Example 1, Example 2, Example 3 and Control Example 1.

[0024] Figure 10 The strain scan results are for the wound ointment products of Examples 1, 2, 3 and Control Example 1.

[0025] Figure 11 This is a comparison chart of the swelling capacity of the wound ointment products from Example 1, Example 2, Example 3 and Control Example 1.

[0026] Figure 12 This is a comparison chart of the water loss rates of the wound ointment products from Example 1, Example 2, Example 3, and Control Example 1. Detailed Implementation

[0027] To make the technical means, creative features, objectives and effects of this invention easier to understand, the invention will be further described below with reference to specific embodiments.

[0028] Example 1 A wound ointment containing a traditional Chinese medicine compound to promote chronic wound healing, comprising a hydrogel matrix and a traditional Chinese medicine compound.

[0029] The traditional Chinese medicine compound is composed of the following raw materials in parts by weight: rhubarb 100g, Bletilla striata 60g, Astragalus membranaceus 200g, Salvia miltiorrhiza 100g, cinnamon 30g, and borneol 10g; the hydrogel matrix includes carbomer 940, Bletilla striata polysaccharide and water, with the concentrations of carbomer 940 and Bletilla striata polysaccharide being 5mg / g and 20mg / g, respectively. The Bletilla striata polysaccharide was purchased from Shaanxi Baichuan Biotechnology Co., Ltd., hereinafter the same.

[0030] A wound ointment containing traditional Chinese medicine compound to promote chronic wound healing includes the following steps: 1) Weigh out rhubarb, Bletilla striata, Astragalus membranaceus, Salvia miltiorrhiza, cinnamon, and borneol according to the specified proportions. During extraction, the mass ratio of the raw materials (rhubarb, Bletilla striata, Astragalus membranaceus, Salvia miltiorrhiza, cinnamon, and borneol) to water is 1:5. The extraction temperature is 80℃, and the extraction time is 1.5h. Repeat the extraction twice to obtain a combined extract. Filter the combined extract with slow filter paper and concentrate it. Then freeze-dry it to obtain a compound freeze-dried powder of traditional Chinese medicine (abbreviated as ASR). Each gram of the compound freeze-dried powder contains 5g of raw herbs. Dissolve 0.5g of the freeze-dried powder in 9.5g of water to obtain a total of 10g of the compound extract.

[0031] 2) Add 0.5g of carbomer 940 and 2g of Bletilla striata polysaccharide to 87.5g of water and let stand for 12 hours until completely dissolved, for a total of 90g. Then stir evenly and let stand to obtain the hydrogel matrix. 3) Mix the Chinese herbal compound extract with the hydrogel matrix, totaling 100g, and stir until completely dissolved. Then add triethanolamine to neutralize to neutral. Stir at 500rpm to obtain the wound ointment product loaded with Chinese herbal compound. At this time, the wound ointment contains 5mg / g of Chinese herbal compound freeze-dried powder, that is, 25mg / g of raw drug, which is a low-concentration Chinese herbal compound hydrogel, abbreviated as BSP / CBM / ASR1.

[0032] Example 2 A wound ointment containing a traditional Chinese medicine compound to promote chronic wound healing, comprising a hydrogel matrix and a traditional Chinese medicine compound.

[0033] The traditional Chinese medicine compound is composed of the following raw materials in parts by weight: rhubarb 100g, Bletilla striata 60g, Astragalus membranaceus 200g, Salvia miltiorrhiza 100g, cinnamon 30g, and borneol 10g; the hydrogel matrix includes carbomer 940, Bletilla striata polysaccharide and water, with the concentrations of carbomer 940 and Bletilla striata polysaccharide being 5mg / g and 20mg / g, respectively.

[0034] A wound ointment containing traditional Chinese medicine compound to promote chronic wound healing includes the following steps: 1) Weigh out rhubarb, Bletilla striata, Astragalus membranaceus, Salvia miltiorrhiza, cinnamon, and borneol according to the specified proportions. During extraction, the mass ratio of the raw materials (rhubarb, Bletilla striata, Astragalus membranaceus, Salvia miltiorrhiza, cinnamon, and borneol) to water is 1:5. The extraction temperature is 80℃, and the extraction time is 1.5h. Repeat the extraction twice to obtain a combined extract. Filter the combined extract with slow filter paper and concentrate it. Then freeze-dry it to obtain a compound freeze-dried powder of traditional Chinese medicine (ASR). Each gram of the compound freeze-dried powder contains 5g of raw herbs. Dissolve 1.0g of freeze-dried powder in 9.0g of water to obtain a total of 10g of compound extract of traditional Chinese medicine.

[0035] 2) Add 0.5g of carbomer 940 and 2g of Bletilla striata polysaccharide to 87.5g of water and let stand for 12 hours until completely dissolved, for a total of 90g. Then stir evenly and let stand to obtain the hydrogel matrix. 3) Mix the Chinese herbal compound extract with the hydrogel matrix, totaling 100g, and stir until completely dissolved. Then add triethanolamine to neutralize to neutral. Stir at 500rpm to obtain the wound ointment product loaded with Chinese herbal compound. At this time, the wound ointment contains 10mg / g of Chinese herbal compound freeze-dried powder, that is, 50mg / g of raw drug, which is a medium concentration of Chinese herbal compound hydrogel, abbreviated as BSP / CBM / ASR2.

[0036] Example 3 A wound ointment containing a traditional Chinese medicine compound to promote chronic wound healing, comprising a hydrogel matrix and the traditional Chinese medicine compound.

[0037] The traditional Chinese medicine compound is composed of the following raw materials in parts by weight: rhubarb 100g, Bletilla striata 60g, Astragalus membranaceus 200g, Salvia miltiorrhiza 100g, cinnamon 30g, and borneol 10g; the hydrogel matrix includes carbomer 940, Bletilla striata polysaccharide and water, with the concentrations of carbomer 940 and Bletilla striata polysaccharide being 5mg / g and 20mg / g, respectively.

[0038] A wound ointment containing traditional Chinese medicine compound to promote chronic wound healing includes the following steps: 1) Weigh out rhubarb, Bletilla striata, Astragalus membranaceus, Salvia miltiorrhiza, cinnamon, and borneol according to the specified proportions. During extraction, the mass ratio of the herbal raw materials (rhubarb, Bletilla striata, Astragalus membranaceus, Salvia miltiorrhiza, cinnamon, and borneol) to water is 1:5. The extraction temperature is 80℃, and the extraction time is 1.5 hours. Repeat the extraction twice to obtain a combined extract. Filter the combined extract using slow-release filter paper, concentrate it, and then freeze-dry it to obtain a compound freeze-dried powder of traditional Chinese medicine (ASR). Each gram of the compound freeze-dried powder contains 5g of raw herbs. Dissolve 1.5g of the freeze-dried powder in 8.5g of water, for a total of 10g, to obtain the compound extract of traditional Chinese medicine.

[0039] 2) Add 0.5g of carbomer 940 and 2g of Bletilla striata polysaccharide to 87.5g of water and let stand for 12 hours until completely dissolved, for a total of 90g. Then stir evenly and let stand to obtain the hydrogel matrix. 3) Mix the Chinese herbal compound extract with the hydrogel matrix, totaling 100g, and stir until completely dissolved. Then add triethanolamine to neutralize to neutral. Stir at 500rpm to obtain the wound ointment product loaded with Chinese herbal compound. At this time, the wound ointment contains 15mg / g of Chinese herbal compound freeze-dried powder, that is, 75mg / g of raw drug, which is a medium concentration of Chinese herbal compound hydrogel, abbreviated as BSP / CBM / ASR3.

[0040] Compare with Example 1 The difference between this comparative example and Example 1 is that there is no traditional Chinese medicine compound in this comparative example. In step 3), triethanolamine is directly added to the hydrogel matrix to neutralize it to neutrality, and it is swelled after freeze-drying. The rest is the same as in Example 1. It is abbreviated as BSP / CBM.

[0041] Compare with Example 2 The difference between this comparative example and Example 1 is that, in step 2), the concentrations of Carbomer 940 and Bletilla striata polysaccharide in the hydrogel matrix are 2.5 mg / g Carbomer 940 and 20 mg / g Bletilla striata polysaccharide, respectively. In this comparative example, the prepared product has low viscosity and a thin texture, making it unsuitable for use as a gel product.

[0042] Compare with Example 3 The difference between this comparative example and Example 1 is that in step 1), 2.0g of lyophilized powder was dissolved in 8.0g of water, totaling 10g, to obtain the herbal compound extract. In step 3), the concentration of the herbal compound extract in the hydrogel matrix was 20mg / g of the herbal compound lyophilized powder, i.e., 100mg / g of raw herb. In this comparative example, due to the excessively high content of the herbal compound, a stable gel system could not be prepared.

[0043] Compare with Example 4 The difference between this comparative example and Example 1 is that in step 1), 2.5g of lyophilized powder was dissolved in 7.5g of water, totaling 10g, to obtain the herbal compound extract. In step 3), the concentration of the herbal compound extract in the hydrogel matrix was 25mg / g of the herbal compound lyophilized powder, i.e., 125mg / g of raw herb. In this comparative example, due to the excessively high content of the herbal compound, a stable gel system could not be prepared.

[0044] Compare with Example 5 The difference between this comparative example and Example 1 is that the traditional Chinese medicine compound is composed of the following ingredients in parts by weight: 100g of Polygonum cuspidatum, 60g of Bletilla striata, 200g of Astragalus membranaceus, 100g of Salvia miltiorrhiza, 30g of Cinnamomum cassia, and 10g of Borneol. The rest is the same as in Example 1.

[0045] Compare with Example 6 The difference between this comparative example and Example 1 is that the traditional Chinese medicine compound is composed of the following ingredients in parts by weight: Coptis chinensis 100g, Bletilla striata 60g, Astragalus membranaceus 200g, Salvia miltiorrhiza 100g, Cinnamomum cassia 30g, and Borneol 10g. The rest is the same as in Example 1.

[0046] Compare with Example 7 The difference between this comparative example and Example 1 is that the hydrogel matrix in this comparative example does not contain Bletilla striata polysaccharide, and the concentration of carbomer 940 is 5 mg / g. The rest is the same as in Example 1, and it is abbreviated as CBM.

[0047] (a) The wound ointment products obtained in Examples 1, 2, and 3, and Comparative Examples 1 and 7 were subjected to electron microscopy to observe the microstructure of the products. The results are as follows: Figure 1 As shown in the figure (the CBM group corresponds to Control Example 7, the BSP / CBM group corresponds to Control Example 1, the BSP / CBM / ASR1 group corresponds to Example 1, the BSP / CBM / ASR2 group corresponds to Example 2, and the BSP / CBM / ASR3 group corresponds to Example 3), it can be seen that, as shown in the CBM group, when the hydrogel matrix does not contain Bletilla striata polysaccharide and is molded alone, a harder, more brittle, or more crystalline structure is formed, which appears as a "sharp" cross-section or surface morphology in the SEM image. However, after adding Bletilla striata polysaccharide (BSP) to the hydrogel matrix, as can be seen from Control Example 1 and each example, the cross-section or surface morphology of the resulting wound ointment product becomes smooth, continuous, and "adhesive". It can be seen that the addition of Bletilla striata polysaccharide to the hydrogel matrix improves the flexibility and viscoelasticity of the material, and further improves the cross-linking density and uniformity of the product's gel network.

[0048] In Examples 1-3, the appearance of the prepared wound ointment products is as follows: Figure 2 As shown, the wound ointment product prepared by the present invention is transparent and light yellow, and has stable and uniform properties.

[0049] The wound ointment products prepared in Examples 1-3 were placed into a 20ml syringe, such as... Figure 3 As shown, the results indicate that the wound ointment can be injected through the syringe needle hole and can be processed into any shape, demonstrating good plasticity.

[0050] (II) Burn wounds are a type of chronic wound healing. A rat burn wound model was constructed as a model of chronic wounds to test the therapeutic effect of hydrogels. The application of the wound ointment products prepared in Examples 1-3, Control Examples 1, 5, and 6 on the burn wound model rats was investigated and tested. The specific methods are as follows: Sodium pentobarbital was injected intraperitoneally into rats at a concentration of 1%. After anesthesia, the rats were placed on the operating table and fixed with their abdomen facing down and their backs facing up. Hair removal cream was used to remove hair from the back of the rats. The rats were burned by an electrically heated copper rod at 200℃ for 5 seconds with a diameter of 1 cm. The applied force was equal to the weight of the electrically heated copper rod itself. After modeling, 10 rats were randomly divided into groups and treated with the corresponding drugs. The specific groupings are as follows: the control group received no drug treatment; the SS group received silver sulfadiazine cream; the CBM group received the wound ointment product from Control Example 7; the BSP / CBM group received the wound ointment product from Control Example 1; the BSP / CBM / ASR1 group received the wound ointment product from Example 1; the BSP / CBM / ASR2 group received the wound ointment product from Example 2; and the BSP / CBM / ASR3 group received the wound ointment product from Example 3. The experimental period was 21 days.

[0051] like Figure 4 As shown, the results indicate that there were no significant changes in wound healing in any group on days 1 and 3. On day 14, the wound areas of the BSP / CBM / ASR1, BSP / CBM / ASR2, and BSP / CBM / ASR3 groups were smaller than those of the model group, SS group, CBM group, and BSP / CBM group, and the healing areas of the CBM group and BSP / CBM group were almost the same. On day 21, the wound areas of the BSP / CBM / ASR2 and BSP / CBM / ASR3 groups were the smallest, and the recovery was the best.

[0052] Histological analysis was performed on the wounds of each group after 21 days. The results of hematoxylin-eosin staining of the wound tissues of each group are as follows: Figure 5 As shown, the results of Masson staining are as follows: Figure 6 As shown, based on tissue distribution and cell observation, the effects of each treatment group on burn wound healing showed a gradual improvement.

[0053] HE staining results showed that the Control group exhibited typical post-burn inflammation and tissue destruction, while the SS and CBM groups showed slight repair, but not as effective as the BSP / CBM treatment group in promoting healing. Especially with increasing ASR dosage (ASR1 to ASR3), tissue regeneration and cell recovery were more complete. The BSP / CBM / ASR3 group performed best, almost reaching normal tissue levels. New capillaries began to appear in the BSP / CBM group and were further enhanced in the BSP / CBM / ASR1, BSP / CBM / ASR2, and BSP / CBM / ASR3 groups. New hair follicles were only observed in the BSP / CBM / ASR2 and BSP / CBM / ASR3 groups, indicating that high-dose ASR promoted the regeneration of epidermal appendages, an important marker of functional recovery in burn healing. This suggests that the combination of BSP / CBM and a certain proportion of ASR in this invention can accelerate wound healing by inhibiting inflammation, promoting fibroblast proliferation and collagen deposition.

[0054] Masson trichrome staining results showed that the collagen matrix in the Control group was severely damaged; treatment in the SS and CBM groups could only initiate limited collagen regeneration, and the newly formed collagen was thin and disordered; treatment in the BSP / CBM group could promote collagen synthesis and deposition and improve the dermal matrix structure; treatment with BSP / CBM combined with traditional Chinese medicine compound extracts, especially the BSP / CBM / ASR2 and BSP / CBM / ASR3 groups, not only greatly increased the amount of collagen deposition, but also promoted the maturation and regular arrangement of collagen fibers, making its structure and distribution infinitely close to normal skin tissue.

[0055] (III) The application of the wound ointment products prepared in Example 2, Control Example 5, and Control Example 6 on the burn wound model rats was further investigated and tested. The specific methods were the same as above, and the specific groups were as follows: the model group did not use drug treatment, the rhubarb group was treated with the wound ointment product in Example 2, the Polygonum cuspidatum group was treated with the wound ointment product in Control Example 5, and the Coptis chinensis group was treated with the product in Control Example 6. The experimental period was 9 days.

[0056] like Figure 7 As shown, the results indicate that on days 1, 3, and 7, the burn wounds in each group did not show significant changes due to necrosis and scab formation. On day 9, the rhubarb group was the first to show obvious scab shedding.

[0057] Histological analysis was performed on the wounds of each group on day 9. The results of hematoxylin-eosin staining of the wound tissues of each group are as follows: Figure 8As shown, the results indicate that the rhubarb group of this invention began to shed scabs more quickly than other groups, entered the inflammatory phase faster, and showed wound contraction. Due to the scab shedding phenomenon, the HE-stained tissue sections were more uneven than those of other groups, and a large number of inflammatory cells, mainly neutrophils and macrophages, participated in the inflammatory response, indicating that the necrotic tissue in the rhubarb group sloughed off first, entering the inflammatory phase of wound healing earlier.

[0058] Rhubarb, Polygonum cuspidatum, and Coptis chinensis all have the effects of clearing heat and purging fire, as well as promoting blood circulation and removing blood stasis. However, according to the experimental results, the present invention has a significant therapeutic effect on burn wounds through the synergistic effect of rhubarb and other ingredients, while Polygonum cuspidatum or Coptis chinensis combined with the same other ingredients cannot achieve the same effect.

[0059] (iv) The rheological properties of the wound ointment products of Examples 1, 2, 3 and Control Example 1 were tested using oscillatory shear rheology. The storage modulus G' and loss modulus G” of the wound ointment products were measured as a function of frequency in the frequency range of 0.1 to 10 Hz. Figure 9 As shown. The results indicate that, in the frequency scanning test, the G' value of the wound ointment products in the BSP / CBM group, BSP / CBM / ASR1 group, BSP / CBM / ASR2 group, and BSP / CBM / ASR3 group of this invention is higher than G", proving the stability of the hydrogel.

[0060] Within a strain range of 0.1% to 1000%, the storage modulus (G') and loss modulus (G”) of the hydrogel were measured by amplitude scanning, and the results are as follows: Figure 10 As shown, under low strain, the G' value of the BSP / CBM group, BSP / CBM / ASR1 group, BSP / CBM / ASR2 group, and BSP / CBM / ASR3 group is higher than G", and the wound ointment product maintains a solid-like shape. Under high strain, the two curves intersect, and G' exceeds G", indicating a shift towards liquid-like behavior. This shift from solid-like behavior to liquid-like behavior at high frequencies demonstrates the adaptability of hydrogels to mechanical stimulation.

[0061] (v) Statistical analysis was performed on the swelling green of the wound ointment products from Examples 1, 2, 3, and Control Example 1, such as... Figure 11 As shown, the results indicate that the swelling rates of the wound ointment products in the BSP / CBM group, BSP / CBM / ASR1 group, BSP / CBM / ASR2 group, and BSP / CBM / ASR3 group all exceeded 150%, indicating that these four hydrogels have good water absorption capacity, reducing exudation from the wound tissue while maintaining a moist environment to promote wound healing.

[0062] (vi) The water loss rate of the wound ointment products of Examples 1, 2, 3 and Control Example 1 was statistically analyzed, and the results are as follows: Figure 12 As shown, the results indicate that, over time, the water content of the wound ointment products in the BSP / CBM / ASR1, BSP / CBM / ASR2, and BSP / CBM / ASR3 groups, as well as the control BSP / CBM group, gradually decreased, but the water loss rate did not exceed 35% at 36 hours, indicating that the product of the present invention has excellent water retention. The BSP / CBM group had the highest water loss rate between 1 and 12 hours, and at this time, the water loss rate of the BSP / CBM group was consistently higher than that of the BSP / CBM / ASR1, BSP / CBM / ASR2, and BSP / CBM / ASR3 groups, indicating that the wound ointment product loaded with traditional Chinese medicine compound in the present invention has better water retention.

[0063] The foregoing has shown and described the basic principles, main features, and advantages of the present invention. Those skilled in the art should understand that the present invention is not limited to the above embodiments. The embodiments and descriptions in the specification are merely illustrative of the principles of the invention. Various changes and modifications can be made to the invention without departing from its spirit and scope, and all such changes and modifications fall within the scope of the present invention as claimed. The scope of protection of this invention is defined by the appended claims and their equivalents.

Claims

1. A wound ointment containing a traditional Chinese medicine compound that promotes the healing of chronic wounds, characterized in that, It includes a hydrogel matrix and a traditional Chinese medicine compound, which is composed of the following raw materials in parts by weight: rhubarb 5-15 parts, Bletilla striata 4-8 parts, Astragalus membranaceus 15-25 parts, Salvia miltiorrhiza 5-15 parts, cinnamon 1-5 parts, and borneol 0.5-1.5 parts.

2. The wound ointment containing a traditional Chinese medicine compound for promoting chronic wound healing as described in claim 1, characterized in that, The concentration of the traditional Chinese medicine compound in the wound ointment is 25~75mg / g.

3. The wound ointment containing a traditional Chinese medicine compound for promoting chronic wound healing as described in claim 1, characterized in that, The traditional Chinese medicine compound is composed of the following ingredients in parts by weight: 10 parts rhubarb, 6 parts Bletilla striata, 20 parts Astragalus membranaceus, 10 parts Salvia miltiorrhiza, 3 parts cinnamon, and 1 part borneol.

4. The wound ointment containing a traditional Chinese medicine compound for promoting chronic wound healing as described in claim 1, characterized in that, The hydrogel matrix comprises 2.5~10 mg / g carbomer 940, 10~20 mg / g Bletilla striata polysaccharide, and the balance is water.

5. The wound ointment containing a traditional Chinese medicine compound for promoting chronic wound healing as described in claim 4, characterized in that, The hydrogel matrix comprises 5 mg / g carbomer 940, 20 mg / g Bletilla striata polysaccharide, and the remainder is water.

6. The method for preparing a wound ointment containing a traditional Chinese medicine compound for promoting chronic wound healing as described in any one of claims 1 to 5, characterized in that, Includes the following steps: 1) Weigh out rhubarb, Bletilla striata, Astragalus membranaceus, Salvia miltiorrhiza, cinnamon and borneol in proportion, extract with water and freeze dry to obtain freeze-dried powder of Chinese herbal compound extract, dissolve the freeze-dried powder in water to obtain Chinese herbal compound extract; 2) Mix carbomer 940, Bletilla striata polysaccharide and water in a certain proportion and let stand until completely dissolved. Stir evenly and let stand to obtain hydrogel matrix; 3) Mix the Chinese herbal compound extract with the hydrogel matrix until the matrix concentration is 5 mg / g carbomer 940 and 20 mg / g Bletilla striata polysaccharide and different concentrations of Chinese herbal compound extract, stir until completely dissolved, and then add triethanolamine to neutralize to obtain the wound ointment loaded with Chinese herbal compound.

7. The method for preparing the wound ointment containing a traditional Chinese medicine compound for promoting chronic wound healing as described in claim 6, characterized in that, In step 1), during extraction, the mass ratio of the Chinese herbal raw materials, consisting of rhubarb, Bletilla striata, Astragalus membranaceus, Salvia miltiorrhiza, cinnamon, and borneol, to water is 1:5~10. The extraction temperature is 75~85℃, the extraction time is 1h~2h, and the extraction is repeated 1~3 times. After combining the extracts, the extracts are concentrated and freeze-dried.

8. The method for preparing a wound ointment containing a traditional Chinese medicine compound to promote chronic wound healing as described in claim 6, characterized in that, In step 2), the settling time is 10~14h.

9. The method for preparing a wound ointment containing a traditional Chinese medicine compound to promote chronic wound healing as described in claim 6, characterized in that, In step 3), the stirring speed is 300-500 rpm.

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