Composition for promoting wound healing and preparation method and application thereof

Abstract

The invention provides a composition for promoting wound healing and a preparation method and application thereof, and belongs to the technical field of pharmaceutical compositions. The composition capable of promoting wound healing, provided by the invention, is prepared from the following raw materials in parts by weight: 10 to 30 parts of rhizoma polygoni cuspidati, 5 to 25 parts of radix et rhizoma rhei, 10 to 25 parts of cortex phellodendri, 8 to 20 parts of radix scutellariae, 6 to 18 parts of radix sanguisorbae, 9 to 18 parts of gallnut and 1 to 5 parts of borneol. Based on the theories of clearing heat and drying dampness, promoting blood circulation to remove blood stasis and astringing sores and promoting tissue regeneration of traditional Chinese medicine, the seven traditional Chinese medicine raw materials including polygonum cuspidatum, rheum officinale, golden cypress, scutellaria baicalensis, sanguisorba officinalis, gallnut and borneol are combined to form the composition with a multi-target synergistic effect, and the composition has the effects of resisting inflammation and bacteria, promoting tissue regeneration, astringing to stop bleeding and easing pain, and has a good application prospect. A good treatment effect is achieved on various wounds, and an efficient and safe new scheme is provided for treatment of various wounds, especially chronic complex wounds.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical composition technology, specifically relating to a composition for promoting wound healing, its preparation method, and its application. Background Technology

[0002] Wound healing is a repair response process of the body to damage to the skin and mucous membranes, involving multiple complex steps such as inflammatory response, cell proliferation, matrix deposition, and tissue remodeling. Whether caused by traumatic factors (such as cuts, abrasions, burns, etc.), pathological factors (such as diabetic foot ulcers, venous ulcers, pressure sores, etc.), or iatrogenic factors (such as surgical wounds, radiation-induced wounds, etc.), if the healing process is obstructed, it can lead not only to local complications such as pain and infection, but also to serious consequences such as systemic inflammatory responses and organ dysfunction. It can even cause the wound to remain unhealed and develop into a chronic ulcer, significantly reducing the patient's quality of life and increasing the medical burden.

[0003] According to clinical data, the number of patients with chronic wounds worldwide is increasing year by year. Among these, diabetic foot ulcers, venous ulcers, and pressure ulcers typically have a healing period exceeding four weeks, with a reduced healing rate. While traumatic wounds (such as burns and cuts) are mostly acute wounds, improper treatment can lead to a high infection rate, thus transforming them into chronic wounds. Furthermore, special wounds such as tumor wounds and radiation-induced wounds, due to accompanying tissue necrosis and immune dysfunction, are difficult to heal effectively with conventional treatments, posing significant challenges to clinical treatment.

[0004] Currently, clinical methods for promoting wound healing mainly include Western medicine treatment, surgical treatment, and traditional Chinese medicine treatment. Western medicine treatment often uses antibiotics, growth factors, and wound dressings. While antibiotics can control infection, long-term use can easily lead to the growth of drug-resistant bacteria and cannot regulate the overall pathophysiological process of wound healing. Growth factors (such as epidermal growth factor and fibroblast growth factor) can promote cell proliferation, but they are expensive, have a short half-life, are easily inactivated by wound exudate, and have limited efficacy on chronic wounds. Surgical treatment (such as skin grafting and flap transplantation) is mainly used for deep wounds, but it has drawbacks such as large trauma, donor site damage, and postoperative scar formation, and is not suitable for mild to moderate wounds or elderly or frail patients.

[0005] While existing technologies have disclosed traditional Chinese medicine (TCM) compositions for wound healing, these compositions generally suffer from a single target: they may focus solely on antibacterial and anti-inflammatory effects, failing to effectively promote tissue regeneration; or they may focus only on tissue repair, lacking the ability to control wound infection. Especially for chronic wounds such as diabetic foot ulcers and pressure ulcers, the complex pathological mechanisms (e.g., microcirculatory disturbances, immunosuppression, and prolonged infection) require compositions to possess multiple effects simultaneously, including anti-inflammatory, antibacterial, microcirculation improvement, cell proliferation promotion, and hemostatic effects. Existing single- or dual-effect compositions are insufficient to meet clinical needs. Furthermore, most compositions do not clearly specify the appropriate wound type, resulting in insufficient targeting and poor efficacy stability in clinical application.

[0006] Based on this, in order to address the problems of existing wound healing compositions having single efficacy, poor efficacy for complex wounds, insufficient control of irritation, and limited applicability, it is necessary to develop a traditional Chinese medicine composition that has anti-inflammatory and antibacterial effects, promotes tissue regeneration, astringes and stops bleeding, and relieves pain, and is suitable for various wound types. This has become a technical problem that urgently needs to be solved in the field of wound treatment. Summary of the Invention

[0007] The purpose of this invention is to provide a composition that has anti-inflammatory, antibacterial, tissue regeneration promoting, astringent, hemostatic, and analgesic effects, and is suitable for various wound types, and has a significant effect on promoting wound healing for various wounds.

[0008] To achieve the above-mentioned objectives, the present invention provides the following technical solution: The present invention provides a composition for promoting wound healing, comprising the following raw materials in parts by weight: 10-30 parts of Polygonum cuspidatum, 5-25 parts of rhubarb, 10-25 parts of Phellodendron chinense, 8-20 parts of Scutellaria baicalensis, 6-18 parts of Sanguisorba officinalis, 9-18 parts of Galla chinensis, and 1-5 parts of borneol.

[0009] The present invention also provides a method for preparing the above composition, comprising the following steps: crushing and mixing the remaining raw materials except borneol to obtain a mixture, mixing the mixture with vegetable oil and frying, taking the frying liquid and mixing it with borneol to obtain the composition; Alternatively, the raw materials other than borneol can be pulverized and mixed to obtain a mixture. The mixture is then mixed with a solvent and refluxed for extraction. The extract is concentrated to obtain a concentrate. The concentrate, borneol, and ointment base are mixed and heated to obtain a composition.

[0010] Preferably, the weight-to-volume ratio of the mixture to the vegetable oil is 1g:5~50mL; the decoction is performed until the medicinal materials are charred but not carbonized, and the decoction temperature is 80~160℃.

[0011] Preferably, the vegetable oil includes sesame oil, peanut oil, tea oil, or corn oil.

[0012] Preferably, the solvent includes water or ethanol solution; the weight-to-volume ratio of the mixture to the solvent is 1g:5~50mL; the volume fraction of the ethanol solution is 70%~96%; and the reflux extraction time is 1h~3h.

[0013] Preferably, the pulverization is performed by passing the pulverized material through a 10-60 mesh sieve.

[0014] Preferably, the ointment base is at least one selected from stearic acid, liquid paraffin, glycerin, petrolatum, lanolin, and sodium lauryl sulfate.

[0015] Preferably, the volume ratio of the concentrate to the ointment base is 10:5~50; the mixing and heating temperature is 50~80℃. The present invention also provides the use of the above-described composition or preparation method in the preparation of products that promote wound healing and / or treat fungal infections.

[0016] Preferably, the wound includes one or more of the following: lacerations, abrasions, tears, crush injuries, puncture wounds, burns, frostbite, electric shock injuries, radiation injuries, skin and mucous membrane erosions, infected wounds, lower extremity venous ulcers, arterial ulcers, diabetic foot ulcers, pressure ulcers, tumorous wounds, bedsores, and surgical wounds; the fungal infection includes one or more of the following: paronychia, tinea pedis, tinea corporis, and onychomycosis.

[0017] The beneficial effects of this invention are: Based on the theories of traditional Chinese medicine regarding clearing heat and drying dampness, promoting blood circulation and removing blood stasis, and promoting wound healing and tissue regeneration, this invention combines seven Chinese medicinal materials—rhubarb, phellodendron bark, scutellaria root, polygonum cuspidatum, sanguisorba root, gallnut, and borneol—to form a multi-target synergistic composition. This composition possesses anti-inflammatory and antibacterial properties, promotes tissue regeneration, astringes and stops bleeding, and relieves pain. It has a good therapeutic effect on various wounds, providing an efficient and safe new solution for the treatment of various wounds, especially chronic and complex wounds. Detailed Implementation

[0018] The present invention provides a composition for promoting wound healing, comprising the following raw materials in parts by weight: 10-30 parts of Polygonum cuspidatum, 5-25 parts of rhubarb, 10-25 parts of Phellodendron chinense, 8-20 parts of Scutellaria baicalensis, 6-18 parts of Sanguisorba officinalis, 9-18 parts of Galla chinensis, and 1-5 parts of borneol.

[0019] The core advantage of the composition provided by this invention lies in its holistic conditioning and comprehensive treatment, achieving wound healing through multi-target effects such as anti-inflammatory, antibacterial, tissue regeneration promotion, and immune regulation. In the composition of this invention, Polygonum cuspidatum is the principal ingredient, possessing three core effects: anti-inflammatory and antibacterial, blood-activating and stasis-removing, and wound-healing and tissue-regenerating, which meets the key needs of wound healing in controlling infection, improving circulation, and promoting repair. Phellodendron bark, Scutellaria baicalensis, and rhubarb are the assistant herbs, assisting the principal herb in enhancing its heat-clearing, dampness-drying, antibacterial, and anti-inflammatory effects. Together, they form a powerful anti-inflammatory and antibacterial system, addressing the primary obstacles to wound healing, such as infection and inflammatory exudation. Phellodendron bark and Scutellaria baicalensis primarily clear heat, dry dampness, purge fire, and detoxify. Phellodendron bark targets damp-heat accumulation in the wound, while Scutellaria baicalensis also cools the blood and stops bleeding. Together, they enhance the anti-inflammatory and antibacterial effects of the principal herb, reducing wound exudation. Rhubarb has the effects of clearing heat, purging fire, promoting blood circulation, removing blood stasis, astringing sores, and detoxifying. It not only assists the principal herb in enhancing its antibacterial and blood-activating effects but also reduces wound exudation through its astringent properties, creating a dry environment for tissue repair. Gallnut and Sanguisorba officinalis are the adjuvant herbs, assisting the principal and assistant herbs from the perspectives of astringency, hemostasis, blood nourishment, and tissue regeneration. They address the wound repair needs of protecting the wound and promoting regeneration, while also harmonizing the bitter and cold properties of the principal and assistant herbs. Borneol serves as the guiding herb, possessing three functions: guiding the active ingredients of the principal, assistant, and adjuvant herbs to penetrate the skin and mucous membrane barriers and reach the deep wound, thus enhancing the overall efficacy; synergistic effect (its cooling and analgesic effects can quickly relieve wound pain and improve patient compliance; at the same time, it can mildly inhibit bacteria, assisting in enhancing the antibacterial effect of the entire formula); and harmonizing effect (it moderates the bitter and cold properties of the principal, assistant, and adjuvant herbs, reducing stimulation to newly formed tissues in the wound and improving medication safety). It acts as a synergist and guide for the entire formula.

[0020] In summary, the composition of this invention uses Polygonum cuspidatum as the principal ingredient, focusing on controlling inflammation, clearing blood stasis, and promoting repair; Phellodendron chinense, Scutellaria baicalensis, and Rheum palmatum are the assistant ingredients, strengthening anti-inflammatory and antibacterial effects; Galla chinensis and Sanguisorba officinalis are the adjuvant ingredients, protecting the wound and promoting regeneration; Borneol is the guiding ingredient, leading the medicine deeper and enhancing its analgesic effect. This forms a closed-loop combination where the principal and assistant ingredients work synergistically to control the cause of the disease, and the adjuvant ingredients protect the wound and promote repair. It is suitable for the complex pathological mechanisms of various wounds, including infectious, traumatic, and chronic ulcer wounds.

[0021] This invention does not specifically limit the source of each raw material in the composition; commercially available products commonly used in the art can be used. In this invention, the preferred amount of Polygonum cuspidatum is 15-25 parts, more preferably 20-22 parts; the preferred amount of Rheum palmatum is 8-20 parts, more preferably 12-16 parts; the preferred amount of Phellodendron chinense is 12-20 parts, more preferably 15-18 parts; the preferred amount of Scutellaria baicalensis is 10-18 parts, more preferably 12-16 parts; the preferred amount of Sanguisorba officinalis is 8-16 parts, more preferably 10-14 parts; the preferred amount of Galla chinensis is 12-16 parts, more preferably 14-15 parts; and the preferred amount of Borneol is 2-4 parts, more preferably 3 parts.

[0022] The present invention also provides a method for preparing the above composition, comprising the following steps: crushing and mixing the remaining raw materials except borneol to obtain a mixture, mixing the mixture with vegetable oil and frying, taking the frying liquid and mixing it with borneol to obtain the composition; Alternatively, the raw materials other than borneol can be pulverized and mixed to obtain a mixture. The mixture is then mixed with a solvent and refluxed for extraction. The extract is concentrated to obtain a concentrate. The concentrate, borneol, and ointment base are mixed and heated to obtain a composition.

[0023] This invention does not specifically limit the pulverization method; conventional pulverization methods in the art are acceptable. In this invention, the pulverized material preferably passes through a 10-60 mesh sieve to facilitate rapid dissolution of bioactive components. In this invention, the weight-to-volume ratio of the mixture to the vegetable oil is preferably 1g:5-50mL, more preferably 1g:10-40mL, and even more preferably 1g:20-30mL; the decoction is preferably performed until the medicinal materials are charred but not carbonized to avoid destruction of the active ingredients; the decoction is preferably performed over a low flame, and the decoction temperature is preferably 80-160℃, more preferably 100-140℃. In this invention, the vegetable oil preferably includes sesame oil, peanut oil, tea oil, or corn oil.

[0024] In this invention, the solvent preferably includes water or an ethanol solution; the volume fraction of the ethanol solution is preferably 70%~96%, more preferably 75%~80%; the weight-to-volume ratio of the mixture to the solvent is preferably 1g:5~50mL, more preferably 1g:10~40mL; the reflux extraction is preferably performed 1~3 times, and the reflux extraction time for each time is preferably 1h~3h, more preferably 1.5h~2.5h. In this invention, the concentration method is preferably vacuum concentration. This invention does not have special requirements for vacuum concentration equipment; conventional vacuum concentration equipment in the art can be used. During vacuum concentration, the temperature is preferably controlled at 45℃~60℃, and ethanol is recovered until there is no alcohol odor. The concentrate removes ethanol while enriching the effective components.

[0025] In this invention, the ointment base is preferably at least one selected from stearic acid, liquid paraffin, glycerin, petrolatum, lanolin, and sodium lauryl sulfate. The formulation of the composition of this invention is preferably an oil or ointment, which enhances the moisturizing and protective effect on the wound and provides better treatment for burns. In this invention, the volume ratio of the concentrate to the ointment base is preferably 10:5~50, more preferably 10:15~40; the mixing and heating temperature is preferably 50~80℃, more preferably 60℃~70℃, and even more preferably 62℃~68℃.

[0026] The present invention also provides the use of the above-described composition or preparation method in the preparation of products that promote wound healing and / or treat fungal infections.

[0027] In this invention, the product preferably includes a drug; the wound preferably includes a traumatic wound, a pathological wound, or a surgical wound; the fungal infection includes one or more of paronychia, tinea pedis, tinea corporis, and onychomycosis.

[0028] The traumatic wounds preferably include mechanical injuries, physical injuries, and chemical injuries. Mechanical injuries preferably include cuts, abrasions, lacerations, crush injuries, or puncture wounds; physical injuries preferably include burns, frostbite, electric shock injuries, and radiation injuries; and chemical injuries preferably include skin and mucous membrane corrosion wounds caused by contact with strong acids, strong alkalis, or corrosive chemicals.

[0029] The pathological wounds preferably include infected wounds, vascular wounds, pressure wounds, tumor wounds, or other pathological wounds; among which, infected wounds preferably include skin abscesses, cellulitis, skin erosions caused by fungal / bacterial infections (such as impetigo ulcers, tuberculous skin ulcers), and mucosal ulcers (such as oral ulcers, perianal infection ulcers); vascular wounds preferably include lower extremity venous ulcers (skin ulcers on the lower leg caused by varicose veins), arterial ulcers (dry ulcers of the foot caused by arteriosclerosis obliterans of the lower extremities), and diabetic foot ulcers (diabetic microvascular ulcers). Foot ulcers caused by canal and nerve lesions are prone to infection; pressure wounds (pressure ulcers) refer to skin and subcutaneous tissue ulcers formed in bony prominences (sacrum, coccyx, hip, heel, etc.) due to local pressure and impaired blood circulation in people who are bedridden or sitting for long periods; tumor-related wounds preferably include wounds formed by the rupture of skin or mucous membrane tumors (such as skin cancer ulcers, oral cancer ulcers), or tissue necrosis wounds caused by tumor radiotherapy / chemotherapy; other pathological wounds preferably include skin and mucous membrane ulcers, tuberculous skin ulcers, and bedsores caused by autoimmune diseases (such as lupus erythematosus, Behcet's disease).

[0030] In this invention, surgical wounds preferably include incisions left after various surgical procedures (such as general surgery, orthopedics, obstetrics and gynecology, proctology, etc.), including surgical incisions after suturing, drainage sites, stoma sites and surrounding wounds, as well as wounds caused by poor postoperative healing such as incision dehiscence and infected ulceration.

[0031] The technical solutions provided by the present invention will be described in detail below with reference to the embodiments, but they should not be construed as limiting the scope of protection of the present invention.

[0032] Unless otherwise specified, the following embodiments are all conventional methods.

[0033] Unless otherwise specified, all materials and reagents used in the following examples are commercially available.

[0034] All data in the following examples were analyzed using SPSS 26.0. Quantitative data are expressed as mean ± standard deviation. One-way ANOVA was used for comparisons between groups, and P < 0.05 was considered statistically significant.

[0035] Example 1 A composition for promoting wound healing is made from the following ingredients: 15g Polygonum cuspidatum, 15g Rheum palmatum, 15g Phellodendron chinense, 15g Scutellaria baicalensis, 15g Sanguisorba officinalis, 15g Galla chinensis and 2.5g Borneol; The preparation method is as follows: The herbs Polygonum cuspidatum, rhubarb, Phellodendron chinense, Scutellaria baicalensis, Sanguisorba officinalis, and Galla chinensis were pulverized separately and passed through a 20-mesh sieve. They were then mixed to obtain a mixture. The mixture was then mixed with peanut oil at a weight-volume ratio of 1g:6mL. The mixture was simmered over low heat until the herbs turned yellowish-brown but not carbonized. The simmering temperature was 95-105℃ and the simmering time was 3 hours. The simmering liquid was then mixed with borneol to obtain the final composition.

[0036] Example 2 A composition for promoting wound healing is made from the following ingredients: 10g Polygonum cuspidatum, 5g rhubarb, 10g Phellodendron chinense, 8g Scutellaria baicalensis, 6g Sanguisorba officinalis, 9g Galla chinensis and 1g borneol; The preparation method is as follows: The herbs Polygonum cuspidatum, rhubarb, Phellodendron chinense, Scutellaria baicalensis, Sanguisorba officinalis, and Galla chinensis were pulverized separately and passed through a 10-mesh sieve. They were then mixed to obtain a mixture. The mixture was then mixed with sesame oil at a weight-to-volume ratio of 1g:5mL. The mixture was simmered over low heat until the herbs turned yellowish-brown but not carbonized. The simmering temperature was 80-90℃ and the simmering time was 2 hours. The simmering liquid was then mixed with borneol to obtain the final composition.

[0037] Example 3 A composition for promoting wound healing is made from the following ingredients: 30g Polygonum cuspidatum, 25g rhubarb, 25g Phellodendron chinense, 20g Scutellaria baicalensis, 18g Sanguisorba officinalis, 18g Galla chinensis and 5g borneol; The preparation method is as follows: Polygonum cuspidatum, rhubarb, phellodendron bark, scutellaria baicalensis, sanguisorba officinalis, and gallnut were pulverized separately and passed through a 60-mesh sieve. The mixture was then mixed with corn oil at a weight-volume ratio of 1g:50mL. The mixture was simmered over low heat until the herbs turned yellowish-brown but not carbonized. The simmering temperature was 150-160℃ and the simmering time was 3 hours. The simmering liquid was then mixed with borneol to obtain the final composition.

[0038] Example 4 A composition for promoting wound healing is made from the following ingredients: 15g Polygonum cuspidatum, 15g Rheum palmatum, 15g Phellodendron chinense, 15g Scutellaria baicalensis, 15g Sanguisorba officinalis, 15g Galla chinensis and 2.5g Borneol; The preparation method is as follows: Polygonum cuspidatum, rhubarb, phellodendron bark, scutellaria baicalensis, sanguisorba officinalis, and gallnut were pulverized separately and passed through a 50-mesh sieve, then mixed to obtain a mixture. The mixture was then mixed with water and refluxed for extraction, with a weight-to-volume ratio of 1g:20mL. The mixture was refluxed twice, with each reflux extraction lasting 2 hours. The extract was then concentrated under reduced pressure at 55℃ to obtain a concentrate. The concentrate, borneol, and petrolatum were mixed and heated to 70℃, with a volume ratio of 10:25 between the concentrate and the ointment base, to obtain the composition.

[0039] Example 5 A composition for promoting wound healing is made from the following ingredients: 15g Polygonum cuspidatum, 15g Rheum palmatum, 15g Phellodendron chinense, 15g Scutellaria baicalensis, 15g Sanguisorba officinalis, 15g Galla chinensis and 2.5g Borneol; The preparation method is as follows: Polygonum cuspidatum, rhubarb, phellodendron bark, scutellaria baicalensis, sanguisorba officinalis, and gallnut were pulverized separately and passed through a 50-mesh sieve, then mixed to obtain a mixture. The mixture was then mixed with an 80% ethanol solution and refluxed for extraction. The weight-volume ratio of the mixture to the ethanol solution was 1 g:30 mL. The mixture was refluxed twice, with each reflux extraction lasting 1 hour. The extract was then concentrated under reduced pressure at 55°C to recover the ethanol until no alcohol odor remained, yielding a concentrated solution. The concentrated solution, borneol, and liquid paraffin were mixed and heated to 60°C. The volume ratio of the concentrated solution to the ointment base was 10:35, yielding the final composition.

[0040] Example 6 A composition for promoting wound healing is made from the following ingredients: 30g Polygonum cuspidatum, 5g rhubarb, 25g Phellodendron chinense, 8g Scutellaria baicalensis, 6g Sanguisorba officinalis, 9g Galla chinensis and 1g borneol; The preparation method is as follows: Polygonum cuspidatum, rhubarb, phellodendron bark, scutellaria baicalensis, sanguisorba officinalis, and gallnut were pulverized separately and passed through a 10-mesh sieve, then mixed to obtain a mixture. The mixture was then mixed with water and refluxed for extraction, with a weight-to-volume ratio of 1g:50mL. The mixture was refluxed twice, with each reflux extraction lasting 3 hours. The extract was then concentrated under reduced pressure at 55℃ to obtain a concentrate. The concentrate, borneol, and petrolatum were mixed and heated to 50℃, with a volume ratio of 10:50 between the concentrate and the ointment base, to obtain the composition.

[0041] Comparative Example 1 The difference from Example 1 is that it does not contain Polygonum cuspidatum, but otherwise it is the same as Example 1.

[0042] Comparative Example 2 The difference from Example 1 is that the amount of Polygonum cuspidatum added is adjusted to 40g, and the rest is the same as Example 1.

[0043] Comparative Example 3 The difference from Example 1 is that the amount of rhubarb added is adjusted to 30g, while the rest is the same as in Example 1.

[0044] Comparative Example 4 The difference from Example 1 is that peanut oil is replaced with cottonseed oil, and the rest is the same as in Example 1.

[0045] Comparative Example 5 The difference from Example 1 is that after mixing all the traditional Chinese medicine raw materials, they are decocted with water, and the rest is the same as in Example 1.

[0046] Comparative Example 6 The difference from Example 5 is that the volume fraction of the ethanol solution is adjusted to 50%, and the rest is the same as in Example 5.

[0047] Test Example 1 Multiple complete skin irritation tests of the composition obtained in Example 1 I. Equipment and animals 1. Test sample: The composition obtained in Example 1.

[0048] 2. Animals: 10 Japanese white rabbits, female, weighing 2.0 kg - 2.5 kg, provided by Beijing Changyang Xishan Breeding Farm, ordinary-grade animals, production license number SCXK(Beijing)2021-0008, quality certificate number 110329251100006618. The feed is provided by Spbio(Beijing) Biotechnology Co., Ltd., production license number SCXK(Beijing)2024-0001, quality certificate number 1103242500157171. The temperature in the animal house is 19°C - 26°C, and the relative humidity is 40% - 70%. 12 hours of lighting and 12 hours of darkness. The animals are allowed to eat freely and drink freely.

[0049] 3. Reagents and instruments: Electronic balance (model: PL6001E, serial number: DL013).

[0050] II. Methods 1. Detection basis: Item 2.3.3.3.3 of the "Disinfection Technical Specification" (2002 edition).

[0051] 2. Preparation of test sample: Directly use the original solution of the test sample.

[0052] 3. Poisoning method: 24 hours before the test, depilate the skin on both sides of the spine of the Japanese white rabbits, with an area of about 3 cm × 3 cm. The next day, apply 0.5 mL of the original solution of the sample in Example 1 on the left side of the skin, and the right side is used as a blank control. After 4 hours of application, wash with warm water to remove the remaining test sample. Apply once a day, with the same method as described above, and apply continuously for 14 days. In order to facilitate the application of the test sample and the observation of the results, depilate again if necessary.

[0053] 4. Observation and evaluation: Observe the skin reaction and score it 24 hours after each application. The scoring criteria and irritation intensity classification refer to Tables 2-11 and 2-12 in "Skin Irritation Test" of 2.3.3 of "Disinfection Technical Specifications" (2002 edition).

[0054] III. Results Multiple skin irritation tests were conducted on 10 animals, and local skin reactions were observed 24 hours after each application. No irritation was observed on either the treated or control side in any of the 10 animals after 14 days, as shown in Table 1. This indicates that the composition provided by this invention is safe and has no skin irritation.

[0055] Table 1. Scoring results of repeated complete skin stimulation responses in Japanese rabbits.

[0056] Experimental Example 2 Antibacterial and healing-promoting tests of the compositions obtained in Examples 1, 4 and 5 Purchase SPF-grade SD rats (weighing 200-220g, 6-8 weeks old) and acclimate them for 1 week before use.

[0057] Candida albicans (ATCC 10231), Escherichia coli (ATCC 25922), Staphylococcus aureus (ATCC 25923), Pseudomonas aeruginosa (ATCC 27853), and hemolytic streptococci (ATCC 19615) were activated and then prepared into 1×10⁻⁶ serotypes. 8 The five bacterial solutions were then mixed in equal volumes to obtain a mixed bacterial solution with a final concentration of 1×10⁻⁶ CFU / mL. 8 CFU / mL.

[0058] Positive control drug: Mupirocin ointment + recombinant human epidermal growth factor gel, mixed at a ratio of 1:1.

[0059] Blank emulsion: Contains only peanut oil and sterile water, and is prepared in the same way as in Example 1.

[0060] 1. Model Building: Hair was removed from the back of rats (area 3cm×3cm). After intraperitoneal anesthesia with sodium pentobarbital, two full-thickness skin defects with a diameter of 1cm were created using a sterile scalpel (reaching the fascia to avoid damaging large blood vessels). 100μL of mixed bacterial solution was dripped into each wound, spread evenly, and exposed for 30 minutes to ensure bacterial colonization, thus constructing a mixed infection wound model.

[0061] 2. Drug administration and sample collection: Immediately after modeling, the drugs were administered: the experimental groups were coated with the compositions obtained in Examples 1, 4, and 5 of this invention, respectively, at a dose of 0.1 g / wound; the positive control group was coated with the positive control drug, at a dose of 0.1 g / wound; and the blank group was coated with the blank emulsion, at a dose of 0.1 g / wound. The drugs were administered once daily for 14 consecutive days.

[0062] On day 14 after drug administration, 10 rats were randomly selected from each group. Wound secretions were wiped with sterile cotton swabs, washed off with 1 mL of sterile physiological saline, serially diluted, and spread onto universal culture medium. The mixture was incubated at 37°C for 24 hours, and total bacterial count (CFU / cm³) was performed. 2 Simultaneously, the cultures were inoculated into the corresponding selective media for each strain, purified, and cultured for 48 hours. Individual bacterial counts (CFU / cm³) were then performed. 2 ).

[0063] 3. Effect assessment: (1) Antibacterial effect: The statistical results of the number of bacterial colonies in wound secretions are shown in Table 2. As can be seen from Table 2, the compositions of Examples 1, 4 and 5 of the present invention have significant antibacterial effects on wounds, and the antibacterial effect is better than that of the positive control group.

[0064] Table 2 Results of bacterial colony count in wound secretions

[0065] Note: This indicates that p < 0.05 compared to the control group.

[0066] (2) Wound healing rate: On days 3, 7, and 14 after administration, the wound contours of 10 mice in each group were traced using transparent membranes. The wound area was calculated using ImageJ software. The healing rate was calculated as (initial area - remaining area) / initial area × 100%. The results are shown in Table 3. As can be seen from Table 3, the compositions of Examples 1, 4, and 5 of this invention have a significant effect on promoting wound healing, and the effect on promoting wound healing is better than that of the positive control group.

[0067] Table 3. Statistical results of wound healing rate

[0068] Note: This indicates that p < 0.05 compared to the control group.

[0069] Experimental Example 3 Treatment of diabetic foot lesions with the compositions obtained in Examples 1, 4 and 5 SPF-grade SD rats, half male and half female, 6-8 weeks old, weighing 200-220g. Adapt to living conditions for 1 week, with an ambient temperature of 22-25℃, humidity of 50%-60%, 12-hour light-dark cycle, and free access to food and water.

[0070] 1. Control reagents: Positive control drugs: mupirocin ointment (Hubei Heng'an Fulin Pharmaceutical Co., Ltd., National Drug Approval Number H20053695) and recombinant human epidermal growth factor gel (Guilin Huaxin Pharmaceutical Co., Ltd., National Drug Approval Number S20020112), mixed evenly at a ratio of 1:1 for later use; Blank control drug: a mixture of corn oil and sterile water, prepared in the same way as in Example 1.

[0071] 2. Grouping: 120 rats were randomly divided into 12 groups, with 10 rats in each group, half male and half female; Normal control group: Non-diabetic rats + full-thickness skin defect wound + blank control drug administration; Model control group: Rats with diabetic foot ulcers + blank control drug administration; Positive control group: Rats with diabetic foot ulcers were given the positive control drug. Example 1 group: Rats with diabetic foot wounds were given the composition of Example 1; Example 4 group: Rats with diabetic foot wounds + administration of the composition of Example 4; Example 5 group: Rats with diabetic foot ulcers were given the composition of Example 5; Comparative Example 1: Rats with diabetic foot ulcers + administered the product of Comparative Example 1; Comparative Example 2: Rats with diabetic foot ulcers + administered the product of Comparative Example 2; Comparative Example 3: Rats with diabetic foot ulcers + administered the product of Comparative Example 3; Comparative Example 4: Rats with diabetic foot ulcers + administered the product of Comparative Example 4; Comparative Example 5: Rats with diabetic foot ulcers + administered the product of Comparative Example 5; Comparative Example 6: Rats with diabetic foot ulcers + administered the product of Comparative Example 6.

[0072] 3. Construction of a diabetic foot wound model: Diabetic model induction: After fasting for 12 hours, rats were intraperitoneally injected with STZ solution (dissolved in 0.1 mol / L citrate buffer, pH 4.5) at a dose of 60 mg / kg; the normal control group was injected with an equal volume of citrate buffer. Blood glucose was measured by collecting blood from the tail tip 72 hours after injection. A diabetic model was considered successful if blood glucose was ≥16.7 mmol / L for 3 consecutive days.

[0073] Wound construction: After the successful establishment of the diabetic model, the rats were shaved on their backs (3cm×3cm), anesthetized intraperitoneally with sodium pentobarbital (30mg / kg), and a full-thickness skin defect with a diameter of 1cm was created using a sterile scalpel (reaching the fascia to avoid damaging major blood vessels); the normal control group was created with only the same size wound.

[0074] 4. Dosing regimen: Drug administration began the day after modeling. All groups received topical application once daily at a dose of 0.1 g per wound for 21 consecutive days. Before administration, the wound was cleaned with sterile saline to remove secretions, and the drug was evenly applied. After administration, the wound was exposed, and an Elizabethan collar was fitted to prevent the rats from scratching.

[0075] Eight rats were randomly selected from each group at 7, 14, and 21 days after drug administration for the following index tests: Wound healing rate: The wound contours of 8 mice in each group were traced using transparent membranes, and the wound area was calculated using ImageJ software. The healing rate was calculated as (initial area - remaining area) / initial area × 100%. The results are shown in Table 4. It can be seen that the wound healing rate of the experimental group increased significantly with the duration of drug administration, and was significantly higher than that of the model control group at each time point. Moreover, the healing rate of the experimental group was better than that of the positive control group.

[0076] Table 4. Statistical results of wound healing rate

[0077] Note: This indicates that p < 0.05 compared to the control group.

[0078] Test Example 4 Drug efficacy test in animal model of fungal paronychia 1. Selection and feeding of laboratory animals: Animal selection: SPF-grade Kunming mice (6-8 weeks old, weighing 18-22g) were selected, with half males and half females, 10 mice in each group, to ensure that the animals were free from periungual skin diseases and systemic infections.

[0079] Rearing environment: temperature 22±2℃, humidity 50%±5%, 12h light / 12h dark cycle, free access to food and water, acclimatization for 3 days before conducting the experiment.

[0080] 2. Preparation of bacterial strains and reagents: Strain activation: The standard strain of Candida albicans (ATCC 90028) was inoculated into Sabouraud dextrose agar (SDA) medium and cultured at 37°C for 24 h. Single colonies were picked and transferred to Sabouraud dextrose broth (SDB) and cultured at 37°C and 150 r / min for 18 h to prepare a bacterial suspension.

[0081] Bacterial suspension concentration adjustment: Dilute the bacterial suspension to 1×10⁻⁶ with sterile physiological saline. 8 CFU / mL, concentration calibrated using a hemocytometer, and prepared fresh for immediate use.

[0082] Formulation preparation: Experimental groups: the compositions obtained in Examples 1, 4, and 5, respectively; Positive control group: Clotrimazole cream (commercially available, 1% concentration); Model control group: sterile saline (equal volume to the experimental group).

[0083] II. Construction of a Fungal Paronychia Model Animal anesthesia: Inject 50 mg / kg of 1% sodium pentobarbital intraperitoneally. After the animal’s corneal reflex disappears, fix it on the operating table.

[0084] Treatment of periungual wounds: Trim the edge of the mouse's hind limb toenails to the nail groove with sterile ophthalmic scissors, and then gently scrape the skin of the nail groove with sterile sandpaper to create a tiny 0.5mm×0.5mm lesion (to the extent that the skin is slightly red without obvious bleeding).

[0085] Fungal inoculation: Using a sterile micropipette, aspirate 5 μL (mice) of 1 × 10⁻⁶ mol / L solution. 8 Apply a CFU / mL Candida albicans suspension to the broken nail groove and secure it with sterile medical tape to prevent the bacterial solution from leaking out.

[0086] Model determination: After inoculation, animals are fed routinely and observed for 3-5 days. If redness and swelling, mild exudation, and local skin temperature increase appear in the nail groove, and fungal culture is performed on the periungual tissue of 3 random model animals (Candida albicans colonies are visible), the model is considered to be successfully established.

[0087] III. Implementation of the Dosing Regimen Dosage timing: Dosage should begin on the day the model is successfully established.

[0088] Administration method: Apply the corresponding preparation evenly to the affected area of ​​the nail groove using a sterile cotton swab, covering the affected area and 2 mm of surrounding normal skin. Single dose per animal: 0.05 g / toe for mice.

[0089] Dosage frequency: Administer once daily at the same time for 7 consecutive days, during which time observe the animal's mental state, diet, and changes in periungual lesions.

[0090] IV. Evaluation Indicators and Specific Testing Methods Seven days after drug administration, inflammation scores were assessed in different groups of mice. The inflammation scoring criteria are shown in Table 5. Scores were given for the degree of redness and swelling, the amount of exudate, and the wound healing status. The results for each group are expressed as averages. The results are shown in Table 6.

[0091] Table 5 Inflammation Scoring Criteria

[0092] Table 6 Inflammation score results for different groups

[0093] Note: This indicates that p < 0.05 compared to the control group.

[0094] Experimental Example 5 Construction of a guinea pig tinea model Animal pretreatment: Hair was removed from the back of the guinea pig in an area of ​​3cm x 3cm (applied with 8% sodium sulfide solution, washed off after 5 minutes to avoid skin corrosion). The animals were observed for 24 hours after hair removal to ensure that there was no redness or breakage of the skin.

[0095] Skin damage: Gently rub the skin in the hair removal area with sterile sandpaper to cause minor damage to the stratum corneum (to the point of slight redness without bleeding, which enhances the efficiency of fungal colonization).

[0096] Fungal inoculation: Take 200 μL of 1×10 7 A CFU / mL suspension of Trichophyton rubrum (ATCC 28189) was applied evenly to the broken skin and secured with sterile gauze to prevent contamination of the bacterial solution.

[0097] Model validation: After inoculation, the animals were fed routinely and observed for 7 consecutive days. If erythema, desquamation, papules, and itching (increased scratching frequency in guinea pigs) appeared in the hair loss area, and skin scrapings from the lesions were examined for fungal microscopy (hyphae / spores were visible) and fungal culture (Cordyceps militaris colonies were observed), the model was considered successful.

[0098] Dosing timing: Dosing should begin on the day the model is successfully established.

[0099] Administration method: Using sterile cotton swabs, apply the compositions of Examples 1, 4 and 5, 1% terbinafine cream (positive control drug), and physiological saline evenly to the lesion area and the surrounding 1 cm of normal skin in different animal models (corresponding to Group 1, Group 4, Group 5, positive control group and model control group, respectively). Apply 0.2g to each animal once a day for 14 consecutive days. After administration, observe the mental state, diet and changes in skin lesions of the guinea pigs.

[0100] The daily lesion area was measured using transparent mesh paper. The calculation formula is: Healing rate = (Initial lesion area - Daily lesion area) / Initial lesion area × 100%.

[0101] The results, as shown in Table 7, indicate that the composition of the present invention has a significant therapeutic effect on tinea corporis.

[0102] Table 7. Statistical results of healing rate

[0103] Note: This indicates that p < 0.05 compared to the control group.

[0104] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A composition for promoting wound healing, characterized in that, It includes the following raw materials by weight: 10-30 parts Polygonum cuspidatum, 5-25 parts Rheum palmatum, 10-25 parts Phellodendron chinense, 8-20 parts Scutellaria baicalensis, 6-18 parts Sanguisorba officinalis, 9-18 parts Gallnut, and 1-5 parts Borneol.

2. The method for preparing the composition according to claim 1, characterized in that, The process includes the following steps: crushing and mixing the remaining raw materials except for borneol to obtain a mixture; mixing the mixture with vegetable oil and frying it; taking the frying liquid and mixing it with borneol to obtain a composition. Alternatively, the raw materials other than borneol can be pulverized and mixed to obtain a mixture. The mixture is then mixed with a solvent and refluxed for extraction. The extract is concentrated to obtain a concentrate. The concentrate, borneol, and ointment base are mixed and heated to obtain a composition.

3. The preparation method according to claim 2, characterized in that, The weight-to-volume ratio of the mixture to the vegetable oil is 1g:5~50mL; the decoction is performed until the medicinal materials are charred but not carbonized, and the decoction temperature is 80~160℃.

4. The preparation method according to claim 2, characterized in that, The vegetable oils include sesame oil, peanut oil, tea oil, or corn oil.

5. The preparation method according to claim 2, characterized in that, The solvent includes water or ethanol solution; the weight-to-volume ratio of the mixture to the solvent is 1g:5~50mL; the volume fraction of the ethanol solution is 70%~96%; and the reflux extraction time is 1h~3h.

6. The preparation method according to claim 2, characterized in that, The pulverization process involves pulverizing the material and then passing it through a 10-60 mesh sieve.

7. The preparation method according to claim 2, characterized in that, The ointment base is at least one of stearic acid, liquid paraffin, glycerin, petrolatum, lanolin, and sodium lauryl sulfate.

8. The preparation method according to claim 2, characterized in that, The volume ratio of the concentrate to the ointment base is 10:5~50; the mixing and heating temperature is 50~80℃.

9. The use of the composition of claim 1 or the preparation method of any one of claims 2 to 8 in the preparation of products that promote wound healing and / or treat fungal infections.

10. The application according to claim 9, characterized in that, The wounds include one or more of the following: lacerations, abrasions, tears, crush injuries, puncture wounds, burns, scalds, frostbite, electric shock injuries, radiation injuries, skin and mucous membrane erosions, infected wounds, lower extremity venous ulcers, arterial ulcers, diabetic foot ulcers, pressure ulcers, tumorous wounds, bedsores, and surgical wounds; the fungal infections include one or more of the following: paronychia, tinea pedis, tinea corporis, and onychomycosis.

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