TW202245821A - Method for preventing or treating chronic skin ulcer and use of traditional chinese medicine composition in preparing medicine - Google Patents

Abstract

The invention relates to a method for preventing or treating chronic skin ulcer and the use of a traditional Chinese medicine composition in preparing medicine. Use of a traditional Chinese medicine composition in the preparing medicine, the medicine is used for the prevention or treatment of chronic skin ulcers, and the traditional Chinese medicine composition comprises the following materials in parts by weight: 8-30 parts of coptis chinensis, 6-25 parts of garden burnet, 20-50 parts of Kunzhi You, 4-18 parts of angelica sinensis, 5-20 parts of beeswax and 1-5 parts of borneol. The method includes: administering a Chinese medicinal composition to the subject, the traditional Chinese medicinal composition comprising the following raw materials in parts by weight: 8-30 parts of coptis chinensis, 6-25 parts of garden burnet, 20-50 parts of Kunzhi You, 4-18 parts of angelica sinensis, 5-20 parts of beeswax and 1-5 parts of borneol.

Description

Method for preventing or treating chronic skin ulcer and use of traditional Chinese medicine composition in preparing medicine

The invention relates to the field of traditional Chinese medicine, in particular to a method for preventing or treating chronic skin ulcer and the application of the traditional Chinese medicine composition in preparing medicine.

This application claims the priority and rights of patent applications with patent application numbers 202110283359.4 and 202110284410.3 filed with the State Intellectual Property Office of China on March 16, 2021, and is hereby incorporated by reference in its entirety.

Skin ulcers are local tissue defects caused by various reasons. Wounds that have not healed for more than 2 weeks are called chronic skin ulcers, and those that have not healed for more than 1 month are chronic refractory skin ulcers. Chronic skin ulcer is the pathological change of degeneration and necrosis of local tissue caused by the comprehensive action of systemic and local factors. The ischemia, hypoxia and nutrient metabolism disorder of local tissue are caused by trauma, infection, pressure and hemodynamic changes. basic pathological process.

Chronic skin ulcer is a common complication of diabetes, peripheral vascular disease, microbial infection, and radiotherapy. In view of the characteristics of chronic skin ulcers that are difficult to heal and easy to repeat, especially compressive skin ulcers, skin ulcers complicated by diabetes, and venous lower extremity ulcers are the most common. As a clinical frequently-occurring and difficult disease, chronic skin ulcer has become a chronic disease that seriously threatens human health. If it does not heal for a long time, the disease will develop progressively and form gangrene. In severe cases, it will be amputated and disabled, or "cancerous" will endanger the Life is the key and difficult problem to be solved urgently in clinical treatment. At present, debridement, dressing change, skin grafting, laser, hyperbaric oxygen and other methods are mainly used clinically for wounds, but the clinical efficacy is not satisfactory and the wound healing rate is low.

Diabetic foot ulcers (diabetic foot ulcers, DFUs) refer to the ulcers that occur below the ankle joint in diabetic patients under the joint action of lower extremity vascular disease, neuropathy and infection. Diabetic foot remains one of the most serious complications of diabetes. When in a state of long-term hyperglycemia, it will lead to weakening or even loss of peripheral nerve sensation in the patient's body, and reduce the circulation ability of the body's peripheral blood vessels, thereby causing ischemia and neurotrophic disorders in the limbs, and secondary infection symptoms. Patients undergo surgical treatment, repair wounds, and even amputation, resulting in high disability and mortality rates.

Pressure sores, also known as pressure ulcers or decubitus ulcers, are due to long-term pressure on local tissues, resulting in continuous ischemia, hypoxia, and malnutrition, resulting in tissue ulceration and necrosis. Skin pressure sores are a common problem in rehabilitation and nursing care. Pressure sores are divided into four stages, the first stage (congestion and ruddy stage): intact skin, damaged blood vessels, finger pressure, red marks that do not turn white, and dark skin; the second stage (inflammatory infiltration stage): skin Broken, but not beyond the dermis, blisters may appear, no carrion; third stage (superficial ulcer stage): epidermis and dermis are completely damaged, reaching the subcutaneous tissue, necrotic tissue and pits may appear; fourth stage (necrotic ulcer Stage): Deep to fascia, muscle and bone, the wound penetrates the subcutaneous tissue, there is a wide range of necrosis, with necrotic tissue or black scab.

Venous ulcers of lower extremities (VLU), also known as venous ulcers, are injuries caused by insufficient venous blood supply of the lower extremities, and are related to chronic venous insufficiency (CVI) of the lower extremities, abnormal venous valve function, and thrombosis of the lower extremities. VLU usually manifests as pigmentation of the lower extremities, seborrheic sclerosis, skin ulceration accompanied by exudate, pain, itching and even odor. At present, many studies believe that the occurrence of VLU is related to gender, age, family history, pregnancy, standing for a long time, lack of exercise, and obesity.

Therefore, there is an urgent need for an effective treatment for chronic skin ulcers.

In order to solve the above-mentioned technical problems, the present invention provides a method for preventing or treating chronic skin ulcers and the application of the traditional Chinese medicine composition in preparing medicines. The method can effectively treat chronic skin ulcers.

The present invention has been accomplished based on the following findings of the inventors:

According to the "Guidelines for Clinical Research of Burn Wounds and Chronic Skin Ulcer Treatment Drugs" issued by the U.S. FDA in June 2006, burns are defined as skin wounds caused by heat, chemical or electrical damage, and chronic skin ulcers are defined as skin wounds caused by heat, chemical or electrical damage, and chronic skin ulcers are Timely administration of a whole set of treatment measures still fails to produce permanently closed wounds in terms of structure, function and aesthetics. Generally speaking, in burns, the short-term contact of the skin with a low-temperature heat source will only cause blister-type burns in the superficial dermis, but if the low-temperature heat source continues to act, it will gradually develop into deep dermis and subcutaneous tissue burns. In the whole process of chronic skin ulcer, there is an interaction of pathogenic factors "deficiency, stasis, and rot". Among them, "deficiency, stasis" are the foundation, and "rot" is the standard. Generally speaking, "deficiency" often determines the "stasis". ", rot" development degree, "stasis" often runs through the disease from beginning to end. Therefore, the pathophysiology of burns and chronic skin ulcers is different.

In view of this, although some technologies for treating chronic skin ulcers (such as CN105362410B) have been disclosed in the prior art, due to the different pathophysiological characteristics of burns and chronic skin ulcers, it is not possible to use the technology for treating chronic skin ulcers. Technology is applied to the treatment of chronic skin ulcers, that is, there is no reference value. Based on this, the inventor took how to treat chronic skin ulcers as a starting point, conducted in-depth research on the existing technologies related to chronic skin ulcer diseases, and obtained a traditional Chinese medicine composition with good therapeutic effect, which can effectively promote ulcer wound healing, and It relieves the pain of dressing change, has good safety and is convenient to use; no skin irritation and adverse reactions occurred during the medication observation period.

However, in the first aspect of the present invention, the present invention proposes the use of a Chinese medicine composition in the preparation of medicines for the prevention or treatment of chronic skin ulcers, the Chinese medicine composition comprising the following raw materials in parts by weight: Coptidis 8 ~30 parts, 6~25 parts of Burnet, 20~50 parts of kunzhi oil, 4~18 parts of angelica, 5~20 parts of beeswax, 1~5 parts of borneol. Kunzhi oil is a medicinal material resource included in the local medicinal material standards of Shandong Province in 1995. Its base is fatty acid substances obtained by refining the mature larvae of Musca domestica Viciua, an insect of the housefly family.

In a second aspect of the present invention, the present invention proposes a method of preventing or treating chronic skin ulcers. According to an embodiment of the present invention, the method includes: administering a traditional Chinese medicine composition to the subject, the traditional Chinese medicine composition including the following raw materials in parts by weight: 8-30 parts of Coptidis Rhizome, 6-25 parts of Burnet, 20-50 parts of Kunzhi Oil 4-18 parts of angelica, 5-20 parts of beeswax, and 1-5 parts of borneol.

Beneficial effect 1. The present invention has significant curative effect on chronic skin ulcers, especially in the treatment of diabetic skin ulcers, pressure ulcers, decubitus ulcers, venous ulcers, and insufficient ulcers. It can promote the healing of ulcer wounds and relieve the pain of changing dressings. 2. The traditional Chinese medicine composition of the present invention has good safety in treating chronic skin ulcers and is convenient to use; no skin irritation or adverse reaction occurs during the medication observation period.

Additional aspects and advantages of the invention will be set forth in the description which follows, and in part will be obvious from the description, or may be learned by practice of the invention.

Embodiments of the present invention are described in detail below. The embodiments described below are exemplary only for explaining the present invention and should not be construed as limiting the present invention.

It should be noted that the terms "first" and "second" are only used for descriptive purposes, and cannot be understood as indicating or implying relative importance or implicitly indicating the quantity of indicated technical features. Thus, a feature defined as "first" and "second" may explicitly or implicitly include one or more of these features. Further, in the description of the present invention, unless otherwise specified, "plurality" means two or more.

As used herein, the term "diabetic ulcer" refers to skin ulcers caused by diabetes, including but not limited to diabetic feet and diabetic bedsores.

As used herein, the term "venous ulcer" refers to skin changes and ongoing ulcers caused by venous disease, including but not limited to venous leg ulcers.

As used herein, the term "optionally", "optionally" or "optionally" means that the subsequently described event or circumstance may but need not occur, and that the description includes the circumstances in which it occurs, and the circumstances in which it occurs The circumstances in which the event or condition did not occur.

As used herein, the term "pharmaceutically acceptable" means that the substance or composition must be chemically and/or toxicologically compatible with the other ingredients comprising the formulation and/or with the mammal being treated therewith. Preferably, "pharmaceutically acceptable" in the present invention refers to those approved by federal regulatory agencies or national governments, or listed in the US Pharmacopoeia or other generally recognized pharmacopoeias for use in animals, especially humans.

For other pharmaceutically acceptable excipients or techniques mentioned herein reference is made to the extensive literature on the subject, in particular Handbook of Pharmaceutical Excipients, 3rd Edition, edited by Arthur H. Kibbe, American Pharmaceutical Association, Washington, USA and Pharmaceutical Press, London; and Lexikon der Hilfsstoffe für Pharmazie, Kosmetik and angrenzende Gebiete, edited by H.P. Fiedler, 4th edition, edited by Cantor, Aulendorf and earlier editions.

In this article, the term "comprising" or "comprising" is an open expression, that is, it includes the content specified in the present invention, but does not exclude other aspects of the content.

As used herein, the term "treatment" is used to refer to obtaining a desired pharmacological and/or physiological effect. The effect may be prophylactic in terms of complete or partial prevention of the disease or its symptoms, and/or therapeutic in terms of partial or complete cure of the disease and/or adverse effects caused by the disease. "Treatment" as used herein encompasses disease in mammals, especially humans, including: (a) preventing the disease or condition in a predisposed but undiagnosed individual; (b) inhibiting the disease, e.g., arresting its progression; Or (c) ameliorating the disease, eg, alleviating symptoms associated with the disease. "Treatment" as used herein encompasses any administration of a drug or compound to an individual to treat, cure, alleviate, ameliorate, alleviate or inhibit a disease in that individual, including but not limited to administering a drug comprising a compound described herein to an individual in need thereof.

As used herein, the term "administering" means introducing a predetermined amount of a substance into a patient by some suitable means. The traditional Chinese medicine composition of the present invention can be administered through any common route, as long as it can reach the expected tissue. Various modes of administration are contemplated, including, but not limited to, administration of the compositions of the present invention by means of rubbing.

The present invention proposes a method for preventing or treating chronic skin ulcers, which will be described in detail below.

Application of traditional Chinese medicine composition in preparation of medicine In the first aspect of the present invention, the present invention proposes the use of a traditional Chinese medicine composition in the preparation of medicines, the medicine is used to prevent or treat chronic skin ulcers, and the Chinese medicine composition includes the following raw materials in parts by weight: Coptidis 8-30 6-25 parts of burnet, 20-50 parts of kunzhi oil, 4-18 parts of angelica, 5-20 parts of beeswax, and 1-5 parts of borneol. The inventor found through experiments that applying the above-mentioned medicine to the wound surface of chronic skin ulcer can promote wound healing and relieve the pain of dressing change, thereby effectively treating chronic skin ulcer.

According to an embodiment of the present invention, the medicament is used for preventing or treating chronic skin ulcers with a course of disease ≥ 30 days.

According to an embodiment of the present invention, the medicament is used to promote wound healing of chronic skin ulcer and/or relieve pain;

According to an embodiment of the present invention, the medicament is used for promoting new epithelium on chronic skin ulcer wounds or reducing scar formation.

According to an embodiment of the present invention, the chronic skin ulcer is selected from deep or mixed ulcers.

It should be noted that chronic skin ulcers include superficial skin ulcers, deep ulcers, and deep ulcers. Among them, superficial skin ulcers have no infection symptoms, deep ulcers are often combined with soft tissue inflammation, but no abscess or bone infection, and deep ulcers usually Refers to ulcers with abscesses or osteomyelitis, localized gangrene. The "mixed ulcer" referred to in the present invention generally refers to an ulcer containing at least two types, for example, a deep ulcer and a deeper ulcer.

According to an embodiment of the present invention, the area of a single ulcer of the chronic skin ulcer is 1-40 cm ² .

According to an embodiment of the present invention, the chronic skin ulcers include at least one of diabetic skin ulcers, pressure sore ulcers, venous ulcers, decubitus ulcers, and hypovascular ulcers. The inventor found through experiments that the medicament of the present invention can promote wound healing and effectively treat diabetic skin ulcers, pressure sore ulcers, venous ulcers and insufficient blood supply ulcers.

According to an embodiment of the present invention, the diabetic skin ulcer includes diabetic foot or diabetic bed sore.

It should be noted that the diabetic foot in the present invention includes grade 1-4 diabetic foot ulcers. Among them, grade 1 diabetic foot ulcers are superficial skin ulcers without infection; grade 2 diabetic foot ulcers are deep ulcers, often accompanied by soft tissue inflammation, without abscess or bone infection; grade 3 diabetic foot ulcers are deep ulcers with Abscess or osteomyelitis; grade 4 diabetic foot ulcer is localized gangrene (toes, heel, dorsum of foot).

According to an embodiment of the present invention, the pressure sore ulcer includes a stage II pressure sore or a stage III pressure sore.

According to an embodiment of the present invention, the pressure sore ulcer includes partial or full-thickness loss of the skin, preferably, the pressure sore ulcer is selected from the superficial shape of the bridge of the nose, ears, occiput and/or ankle bone a stage III pressure ulcer; alternatively, the pressure sore ulcer is selected from a fatty area of deep stage III pressure ulcer.

It should be noted that "partial cortical loss" refers to the appearance of superficial open ulcers, the wound surface is pink, without slough, and it can also appear as complete or open/broken serous blisters, with a clear or dry appearance Superficial ulceration without slough and bruises (bruises suggest suspected deep tissue injury); "full-thickness loss" means subcutaneous fat is visible but bone, tendon, and muscle are not exposed, slough may be present but tissue is not hidden missing depth.

According to an embodiment of the present invention, the venous ulcer includes a venous ulcer of lower extremities.

According to an embodiment of the present invention, the venous ulcer of the lower extremity is selected from the venous ulcer of the lower extremity of the patient with an ankle-brachial index (ABI) ≥ 0.8.

According to an embodiment of the present invention, the traditional Chinese medicine composition includes the following raw materials in parts by weight: 10-18 parts of Coptidis rhizome, 7-13 parts of Burnet, 21-38 parts of kunzhi oil, 4-9 parts of angelica, 5-12 parts of beeswax, 1~2 parts of borneol. The inventor obtained the above-mentioned optimal ratio through a large number of experiments, thus, the wound healing of chronic skin ulcers can be further promoted, and the therapeutic effect on chronic skin ulcers can be improved.

According to an embodiment of the present invention, the traditional Chinese medicine composition includes the following raw materials in parts by weight: 12-15 parts of Coptidis rhizome, 10-12 parts of Burnet, 28-32 parts of kunzhi oil, 6-8 parts of angelica, 7-9 parts of beeswax, 1.2~1.8 parts of borneol. The inventor obtained the above-mentioned optimal ratio through a large number of experiments, thus, the wound healing of chronic skin ulcers can be further promoted, and the therapeutic effect on chronic skin ulcers can be improved.

According to an embodiment of the present invention, the traditional Chinese medicine composition further includes 27-65 parts by weight of pharmaceutically acceptable excipients, preferably 40-55 parts by weight.

According to an embodiment of the present invention, the excipient includes at least one of an oily base, a water-soluble base and an emulsion base.

It should be explained that the oily base includes, but is not limited to, at least one of pod fat, vegetable oil, hydrogenated vegetable oil, lanolin, beeswax, spermaceti, insect wax, petrolatum and silicones.

It should be explained that the water-soluble base includes but not limited to cellulose and/or polyethylene glycol.

It should be explained that the emulsion base includes but not limited to stearic acid and/or higher alcohols.

According to an embodiment of the present invention, the auxiliary material is selected from vegetable oil.

According to an embodiment of the present invention, the vegetable oil includes olive oil, soybean oil, thorn fruit oil, linseed oil, sunflower oil, jojoba oil, peanut oil, tea oil, tea tree oil, rosehip oil, nut oil, At least one of avocado oil, castor oil, sesame oil, salad oil, corn germ oil and corn oil.

According to an embodiment of the present invention, the dosage form of the drug includes at least one of ointment, cream, oil and patch. Creams include ointments or plasters.

According to an embodiment of the present invention, the dosage form of the drug is selected from ointment.

According to an embodiment of the present invention, the route of administration of the drug is selected from smearing.

According to an embodiment of the present invention, the thickness of the smearing is 1-3mm.

According to an embodiment of the present invention, the traditional Chinese medicine composition comprises the following preparation steps: (1) extracting the Angelica sinensis, respectively collecting the dregs I, water extract, volatile oil and saturated aqueous solution for later use; (2) extracting the Coptidis Rhizome , Burnet and dregs I are decocted, and the collected filtrate and the water extract are concentrated to obtain a thick paste; (3) the volatile oil, saturated aqueous solution, thick paste, and borneol are mixed to obtain a standby liquid; (4) Mix the kunzhi oil, beeswax and stock solution to obtain the traditional Chinese medicine composition.

According to an embodiment of the present invention, in step (2), the number of decocting in the decocting treatment is 1-3 times, and the decocting time is 1-3 hours.

According to an embodiment of the present invention, the step (2) further includes: performing the first decoction treatment on the Coptidis Rhizoma and Burnet, and obtaining the filtrate I and medicinal residues II after the first filtration treatment; The dregs I are mixed for the second decoction treatment, and the second filtration treatment is to obtain the filtrate II; the filtrate I, the filtrate II and the water extract are mixed and concentrated into a clear paste; the clear paste is subjected to alcohol precipitation treatment, and the third After filtration, the obtained filtrate III was concentrated under reduced pressure to obtain a thick paste.

According to an embodiment of the present invention, the solvent used in the alcohol precipitation treatment is 70-100% ethanol solution, and the alcohol precipitation treatment reaches an ethanol concentration of 40-60%.

According to an embodiment of the present invention, the third filtration treatment includes heat filtration and/or heat preservation treatment.

According to an embodiment of the present invention, the precipitate obtained after the heat filtration treatment is washed with aqueous ethanol, and the filtrate is obtained after filtration, and the filtrate is combined with the hot filtrate obtained by the heat filtration treatment to obtain the filtrate III.

According to an embodiment of the present invention, the temperature of the hot filtration is 60°C-85°C, and the washing treatment is performed with 40-50% ethanol.

According to an embodiment of the present invention, the first decocting treatment is performed twice, and the decocting time is 1-1.5 hours each time.

According to an embodiment of the present invention, the time for the second decocting treatment is 1-1.5 hours.

According to an embodiment of the present invention, the relative density of the clear ointment at 40°C-50°C is 1.02-1.15, and the relative density of the thick ointment at 40°C-50°C is 1.10-1.25.

According to an embodiment of the present invention, step (4) further includes heating and co-melting the kun fat oil and beeswax, mixing them uniformly and then cooling them, and mixing the obtained mixed solution with the standby solution to obtain the traditional Chinese medicine combination things.

It should be noted that the heating temperature of "heating eutectic" can only melt the quinoa oil and beeswax, and is not specifically limited.

According to an embodiment of the present invention, the adjuvant is mixed with the quinoa oil and beeswax.

According to an embodiment of the present invention, the temperature of the cooling treatment is 30°C-75°C.

Methods of preventing or treating chronic skin ulcers In the second aspect of the present invention, the present invention proposes a method for preventing or treating chronic skin ulcers, which is characterized in that it includes: administering a Chinese medicine composition to a subject, and the Chinese medicine composition includes the following raw materials in parts by weight: Coptidis 8 ~30 parts, 6~25 parts of Burnet, 20~50 parts of kunzhi oil, 4~18 parts of angelica, 5~20 parts of beeswax, 1~5 parts of borneol. The inventor found through experiments that applying the above-mentioned traditional Chinese medicine composition on the wound surface of chronic skin ulcer can promote wound healing and relieve the pain of dressing change, thereby effectively treating chronic skin ulcer.

According to an embodiment of the present invention, the traditional Chinese medicine composition is used for preventing or treating chronic skin ulcers with a course of disease ≥ 30 days.

According to an embodiment of the present invention, the traditional Chinese medicine composition is used for promoting wound healing of chronic skin ulcer and/or alleviating pain.

According to an embodiment of the present invention, the traditional Chinese medicine composition is used to promote new epithelium on wound surface or reduce scar formation.

According to an embodiment of the present invention, the dosage form of the traditional Chinese medicine composition is selected from ointment.

According to an embodiment of the present invention, the route of administration of the traditional Chinese medicine composition is selected from daubing.

According to an embodiment of the present invention, the thickness of the smearing is 1-3mm.

Those with ordinary knowledge in the technical field of the present invention can understand that the characteristics and advantages described above for the use of the traditional Chinese medicine composition in the preparation of medicines are also applicable to the method for preventing or treating chronic skin ulcers, and are not repeated here. repeat.

The solutions of the present invention will be explained below in conjunction with examples. Those skilled in the art to which the present invention pertains will understand that the following examples are only for illustrating the present invention, and should not be considered as limiting the scope of the present invention. If no specific technique or condition is indicated in the examples, it shall be carried out according to the technique or condition described in the literature in this field or according to the product specification. The reagents or instruments used were not indicated by the manufacturer, and they were all commercially available conventional products.

It should be noted that the medicinal effect of the ointment in this application is the traditional Chinese medicine composition, and the auxiliary materials (such as olive oil, sesame oil, etc.) in the following examples are only for the convenience of making an ointment for easy application.

Embodiment 1: the preparation of Chinese medicine composition The raw materials of the traditional Chinese medicine composition include: Coptis chinensis 95g, burnet 70g, kunzhi oil 213g, angelica 48g, beeswax 55g, borneol 10g, olive oil 400g. The above-mentioned traditional Chinese medicine composition is prepared into an ointment, and the process steps of the specific preparation method are as follows: Take angelica and extract volatile oil by distillation, then collect volatile oil, saturated aqueous solution obtained after distillation, dregs I and water extract in another device. Take Coptis chinensis and Burnet elm, add water to decoct twice, decoct for 1.5 hours for the first time, and filter while hot to obtain filtrate I and dregs II respectively; mix dregs II and dregs I for the second time and decoct for 1 hour , filtrate while hot to obtain filtrate II, combine filtrate I, filtrate II and water extract, concentrate to a relative density of clear paste 1.05-1.11 (measured at 40°C); take clear paste and add 100% ethanol for alcohol precipitation to contain 50% alcohol, Perform hot filtration at 60°C to obtain a hot filtrate; wash the precipitate obtained by the above hot filtration with 60°C and 50% ethanol, filter, combine the hot filtrate and filtrate, and concentrate under reduced pressure to 1.14-1.20 (measured at 40°C) thick paste; mix volatile oil, saturated aqueous solution, and thick paste evenly, add finely ground borneol, and mix well as a spare liquid; take beeswax and olive oil, heat and eutectic, mix well, and let cool to 40-45°C Then slowly add the reserve solution, stir and grind while adding until completely dispersed and uniform, continue stirring to below 35°C, subpackage and seal, and after sterilization, an ointment containing the traditional Chinese medicine composition is obtained.

Embodiment 2: the preparation of Chinese medicine composition The raw materials of the traditional Chinese medicine composition include: 120g of coptis, 90g of burnet, 273g of kunzhi oil, 60g of angelica, 70g of beeswax, 12g of borneol, and 480g of olive oil. The above-mentioned traditional Chinese medicine composition is prepared into an ointment, and the process steps of the specific preparation method are as follows: Take angelica and extract volatile oil by distillation, then collect volatile oil, saturated aqueous solution obtained after distillation, dregs I and water extract in another device. Take Coptis chinensis and Burnet elm, add water to decoct twice, decoct for 1.5 hours for the first time, and filter while hot to obtain filtrate I and dregs II respectively; mix dregs II and dregs I for the second time and decoct for 1 hour , filtered while hot to obtain filtrate II, combined filtrate I, filtrate II and water extract, concentrated to a relative density of clear paste 1.02-1.01 (measured at 45°C); take clear paste and add 70% ethanol for alcohol precipitation to 40% alcohol, Perform hot filtration at 65-70°C to obtain hot filtrate; wash the precipitate obtained by the above hot filtration with 50% ethanol (65-70°C), filter, combine hot filtrate and filtrate, and concentrate under reduced pressure to 1.15-1.22 (measured at 35°C) thick ointment; mix volatile oil, saturated aqueous solution, and thick ointment evenly, add finely ground borneol, and mix well as a spare liquid; take beeswax and olive oil, heat and eutectic, mix well, and let cool When the temperature reaches 40-45°C, slowly add the reserve liquid, stir and grind until completely dispersed evenly while adding, continue to stir until below 30°C, subpackage and seal, and after sterilization, an ointment containing the traditional Chinese medicine composition is obtained.

Embodiment 3: the preparation of Chinese medicine composition The raw materials of the traditional Chinese medicine composition include: 140g of coptis, 105g of burnet, 320g of kunzhi oil, 70g of angelica, 80g of beeswax, 15g of borneol, and 435g of sesame oil. The above-mentioned traditional Chinese medicine composition is prepared into an ointment, and the process steps of the specific preparation method are as follows: Take angelica and extract volatile oil by distillation, then collect volatile oil, saturated aqueous solution obtained after distillation, dregs I and water extract in another device. Take Coptis chinensis and Burnet elm, add water to decoct twice, decoct for 1.5 hours for the first time, and filter while hot to obtain filtrate I and dregs II respectively; mix dregs II and dregs I for the second time and decoct for 1 hour , filtered while hot to obtain filtrate II, combined filtrate I, filtrate II and water extract, concentrated to a relative density of clear paste 1.04 ~ 1.08 (measured at 50°C); take clear paste and add 95% ethanol for alcohol precipitation to contain 50% alcohol, Perform hot filtration at 70-75°C to obtain hot filtrate; wash the precipitate obtained by the above hot filtration with 50% ethanol (70-75°C), filter, combine hot filtrate and filtrate, and concentrate under reduced pressure to 1.14-1.20 (measured at 40°C) thick ointment; mix volatile oil, saturated aqueous solution, and thick ointment evenly, add finely ground borneol, and mix well as a spare liquid; take kunzhi oil, beeswax, and sesame oil, heat and eutectic, mix well, and let cool until When the temperature is 50-55°C, slowly add the reserve solution, stir and grind until completely dispersed evenly while adding, continue to stir to 30-40°C, subpackage and seal, and after sterilization, an ointment containing the traditional Chinese medicine composition is obtained.

Embodiment 4: the preparation of Chinese medicine composition The raw materials of the traditional Chinese medicine composition include: 180g of coptis, 100g of burnet, 280g of kunzhi oil, 60g of angelica, 90g of beeswax, 12g of borneol, and 500g of sesame oil. The above-mentioned traditional Chinese medicine composition is prepared into an ointment, and the process steps of the specific preparation method are as follows: Take angelica and extract volatile oil by distillation, then collect volatile oil, saturated aqueous solution obtained after distillation, dregs I and water extract in another device. Take Coptis chinensis and Burnet elm, add water to decoct twice, decoct for 1.5 hours for the first time, and filter while hot to obtain filtrate I and dregs II respectively; mix dregs II and dregs I for the second time and decoct for 1 hour , filtered while hot to obtain filtrate II, combined filtrate I, filtrate II and water extract, concentrated to a relative density of clear paste 1.04-1.18 (measured at 45°C); take clear paste and add 80% ethanol for alcohol precipitation to 40% alcohol, Perform hot filtration at 70-80°C to obtain a hot filtrate; wash the precipitate obtained by the above hot filtration with 40% ethanol (70-80°C), filter, combine the hot filtrate and filtrate, and concentrate under reduced pressure to 1.12-1.18 (measured at 35°C) thick ointment; mix volatile oil, saturated aqueous solution, and thick ointment evenly, add finely ground borneol, and mix well as a spare liquid; take kunzhi oil, beeswax, and sesame oil, heat and eutectic, mix well, and let cool until When the temperature is 55-60°C, add the reserve solution slowly, stir and grind until completely dispersed evenly while adding, continue to stir until below 35°C, sub-package and seal, and after sterilization, an ointment containing the traditional Chinese medicine composition is obtained.

Embodiment 5: the preparation of Chinese medicine composition The raw materials of the traditional Chinese medicine composition include: 130g of coptis, 95g of Burnet, 300g of kunzhi oil, 70g of angelica, 80g of beeswax, 15g of borneol, and 650g of salad oil. The above-mentioned traditional Chinese medicine composition is prepared into an ointment, and the process steps of the specific preparation method are as follows: Take angelica and extract volatile oil by distillation, then collect volatile oil, saturated aqueous solution obtained after distillation, dregs I and water extract in another device. Take Coptis chinensis and Burnet elm, add water to decoct twice, decoct for 1.5 hours for the first time, and filter while hot to obtain filtrate I and dregs II respectively; mix dregs II and dregs I for the second time and decoct for 1 hour , filtered while hot to obtain filtrate II, combined filtrate I, filtrate II and water extract, concentrated to a relative density of clear paste 1.05-1.13 (measured at 45°C); take clear paste and add 95% ethanol for alcohol precipitation to 50% alcohol, Perform hot filtration at 65-70°C to obtain a hot filtrate; wash the precipitate obtained by the above hot filtration with 60% ethanol (65-70°C), filter, combine the hot filtrate and filtrate, and concentrate under reduced pressure to 1.12-1.18 (measured at 35°C) thick ointment; mix volatile oil, saturated aqueous solution, and thick ointment evenly, add finely ground borneol, and mix well as a spare liquid; take kunzhi oil, beeswax and salad oil, heat and eutectic, mix evenly, and let cool When the temperature reaches 55-60°C, slowly add the reserve liquid, stir and grind until completely dispersed evenly while adding, continue to stir until below 35°C, subpackage and seal, and after sterilization, an ointment containing the traditional Chinese medicine composition is obtained.

Embodiment 6: the preparation of Chinese medicine composition The raw materials of the traditional Chinese medicine composition include: 150g of coptis, 110g of burnet, 300g of kunzhi oil, 70g of angelica, 80g of beeswax, 12g of borneol, and 550g of salad oil. The above-mentioned traditional Chinese medicine composition is prepared into an ointment, and the process steps of the specific preparation method are as follows: Take angelica and extract volatile oil by distillation, then collect volatile oil, saturated aqueous solution obtained after distillation, dregs I and water extract in another device. Take Coptis chinensis and Burnet elm, add water to decoct twice, decoct for 1.5 hours for the first time, and filter while hot to obtain filtrate I and dregs II respectively; mix dregs II and dregs I for the second time and decoct for 1 hour , filtered while hot to obtain filtrate II, combined filtrate I, filtrate II and water extract, concentrated to a relative density of clear paste 1.06-1.14 (measured at 45°C); take clear paste and add 70% ethanol for alcohol precipitation to 50% alcohol, Perform hot filtration at 70°C to obtain a hot filtrate; wash the precipitate obtained by the above hot filtration with 50% ethanol (60°C), filter, combine the hot filtrate and filtrate, and concentrate under reduced pressure to 1.14-1.20 (measured at 40°C) ) thick paste; mix volatile oil, saturated aqueous solution, and thick paste evenly, add finely ground borneol, and mix well as a spare liquid; take kunzhi oil, beeswax and salad oil, heat and eutectic, mix well, let cool to 45-50 ℃, then slowly add the reserve solution, while adding, stir and grind until completely dispersed and uniform, continue to stir to below 35 ℃, sub-package and seal, and after sterilization, an ointment containing the traditional Chinese medicine composition is obtained.

Embodiment 7: the preparation of Chinese medicine composition The raw materials of the traditional Chinese medicine composition include: 135g of coptis, 130g of burnet, 260g of kunzhi oil, 60g of angelica, 70g of beeswax, 10g of borneol, and 550g of sesame oil. The above-mentioned traditional Chinese medicine composition is prepared into an ointment, and the process steps of the specific preparation method are as follows: Take angelica and extract volatile oil by distillation, then collect volatile oil, saturated aqueous solution obtained after distillation, dregs I and water extract in another device. Take Coptis chinensis and Burnet elm, add water to decoct twice, decoct for 1.5 hours for the first time, and filter while hot to obtain filtrate I and dregs II respectively; mix dregs II and dregs I for the second time and decoct for 1 hour , filtered while hot to obtain filtrate II, combined filtrate I, filtrate II and water extract, concentrated to a relative density of clear paste 1.06-1.14 (measured at 45°C); take clear paste and add 100% ethanol for alcohol precipitation to contain 50% alcohol, Perform hot filtration at 70°C to obtain a hot filtrate; wash the precipitate obtained by the above hot filtration with 70% ethanol (65°C-75°C), filter, combine the hot filtrate and filtrate, and concentrate under reduced pressure to 1.14-1.20 ( 40 ℃) thick paste; mix volatile oil, saturated aqueous solution, and thick paste evenly, add finely ground borneol, and mix well as a spare liquid; take kunzhi oil, beeswax and sesame oil, heat and eutectic, mix well, let cool to 50 At ~55°C, add the reserve solution slowly, stir and grind while adding until completely dispersed, continue to stir to 35-40°C, subpackage and seal, and after sterilization, an ointment containing the traditional Chinese medicine composition is obtained.

Embodiment 8: the preparation of Chinese medicine composition The raw materials of the traditional Chinese medicine composition include: 150g of coptis, 120g of burnet, 380g of kunzhi oil, 85g of angelica, 95g of beeswax, 18g of borneol, and 520g of castor oil. The above-mentioned traditional Chinese medicine composition is prepared into an ointment, and the process steps of the specific preparation method are as follows: Take angelica and extract volatile oil by distillation, then collect volatile oil, saturated aqueous solution obtained after distillation, dregs I and water extract in another device. Take Coptis chinensis and Burnet elm, add water to decoct twice, decoct for 1.5 hours for the first time, and filter while hot to obtain filtrate I and dregs II respectively; mix dregs II and dregs I for the second time and decoct for 1 hour , filtered while hot to obtain filtrate II, combined filtrate I, filtrate II and water extract, concentrated to a relative density of clear paste 1.06-1.14 (measured at 45°C); take clear paste and add 80% ethanol for alcohol precipitation to 70% alcohol, Perform hot filtration at 60°C to obtain a hot filtrate; wash the precipitate obtained by the above hot filtration with 70% ethanol (60-70°C), filter, combine the hot filtrate and filtrate, and concentrate under reduced pressure to 1.10-1.18 (40 ℃) thick paste; mix volatile oil, saturated aqueous solution, and thick paste evenly, add finely ground borneol, and mix well as a spare liquid; take kunlin oil, beeswax, and castor oil, heat and eutectic, mix well, and let cool to 45 At ~55°C, add the reserve solution slowly, stir and grind while adding until completely dispersed and uniform, continue to stir until below 35°C, subpackage and seal, and after sterilization, an ointment containing the traditional Chinese medicine composition is obtained.

Embodiment 9: the preparation of Chinese medicine composition The raw materials of the traditional Chinese medicine composition include: 140g of coptis, 95g of Burnet, 330g of kunzhi oil, 80g of angelica, 80g of beeswax, 15g of borneol, and 520g of sesame oil. The above-mentioned traditional Chinese medicine composition is prepared into an ointment, and the process steps of the specific preparation method are as follows: Take angelica and extract volatile oil by distillation, then collect volatile oil, saturated aqueous solution obtained after distillation, dregs I and water extract in another device. Take Coptis chinensis and Burnet elm, add water to decoct twice, decoct for 1.5 hours for the first time, and filter while hot to obtain filtrate I and dregs II respectively; mix dregs II and dregs I for the second time and decoct for 1 hour , filtrate while hot to obtain filtrate II, combine filtrate I, filtrate II and water extract, concentrate to a relative density of clear paste 1.05-1.10 (measured at 45°C); take clear paste and add ethanol for alcohol precipitation until the alcohol content is 50%, 60～ Perform hot filtration at 70°C to obtain a hot filtrate; wash the precipitate obtained by the above hot filtration with 50% ethanol (60-70°C), filter, combine the hot filtrate and filtrate, and concentrate under reduced pressure to 1.12-1.18 (40 ℃) thick paste; mix volatile oil, saturated aqueous solution, and thick paste evenly, add finely ground borneol, and mix well as a spare liquid; take kunzhi oil, beeswax and sesame oil, heat and eutectic, mix well, let cool to 45 ~ When the temperature is 55°C, slowly add the reserve liquid, stir and grind until completely dispersed evenly while adding, continue to stir until below 35°C, subpackage and seal, and after sterilization, an ointment containing the traditional Chinese medicine composition is obtained.

Embodiment 10: the preparation of Chinese medicine composition The raw materials of the traditional Chinese medicine composition include: 150g of coptis, 120g of burnet, 380g of kunzhi oil, 85g of angelica, 95g of beeswax, 18g of borneol, and 520g of castor oil. The above-mentioned traditional Chinese medicine composition is prepared into an ointment, and the process steps of the specific preparation method are as follows: Take angelica and extract volatile oil by distillation, then collect volatile oil, saturated aqueous solution obtained after distillation, dregs I and water extract in another device. Take Coptis chinensis and Burnet elm, add water to decoct twice, decoct for 1.5 hours for the first time, and filter while hot to obtain filtrate I and dregs II respectively; mix dregs II and dregs I for the second time and decoct for 1 hour , filtered while hot to obtain filtrate II, combined filtrate I, filtrate II and water extract, concentrated to a relative density of clear paste 1.05-1.10 (measured at 50°C); take clear paste and add 95% ethanol for alcohol precipitation to 60% alcohol, Perform hot filtration at 85°C to obtain a hot filtrate; wash the precipitate obtained by the above hot filtration with 60% ethanol (85-90°C), filter, combine the hot filtrate and filtrate, and concentrate under reduced pressure to 1.12-1.18 (40 ℃) thick paste; mix volatile oil, saturated aqueous solution, and thick paste evenly, add finely ground borneol, and mix well as a spare liquid; take kunlin oil, beeswax, and castor oil, heat and eutectic, mix well, and let cool to 45 At ~55°C, add the reserve solution slowly, stir and grind while adding until completely dispersed and uniform, continue to stir until below 35°C, subpackage and seal, and after sterilization, an ointment containing the traditional Chinese medicine composition is obtained.

Test Example 1: A single-arm, open, self-controlled, multi-center clinical trial of the effectiveness and safety of Chinese medicine composition in treating diabetic foot

1 Subject selection and experimental design 1.1 Qualified subject selection criteria 1.1.1 Diagnostic criteria 1.1.1.1 Diabetic foot diagnostic criteria refer to the "Chinese Expert Consensus on the Prevention and Treatment of Diabetic Foot with Integrated Traditional Chinese and Western Medicine" issued by the Peripheral Vascular Disease Professional Committee of the Chinese Association of Integrated Traditional and Western Medicine (1st Edition)" (2019 Edition). Diabetic foot is the destruction of the skin and deep tissue beyond the ankle joint in diabetic patients, which is usually caused by ischemia and neuropathy, not necessarily associated with infection. Ulcers are induced by trauma, pressure injury, or spontaneous ulcers without a clear cause. In severe ischemia, purpura purpura and dry gangrene may appear directly without ulceration. 1.1.1.2 Diabetic foot Wagner grading standard (1981) Grade 0: There are risk factors for foot ulcers, but no ulcers. Grade 1: Superficial ulceration of the skin without infection. Grade 2: Deep ulcer, often accompanied by soft tissue inflammation, without abscess or bone infection. Grade 3: deep ulcer with abscess or osteomyelitis. Grade 4: localized gangrene (toes, heels, dorsum of feet). Grade 5: Gangrene of most or all feet. 1.1.2 Criteria for test cases 1.1.2.1 Criteria for inclusion of cases 1) Age range 18-75 years old, gender is not limited; 2) Patients who meet the diagnostic criteria for diabetic foot, diabetic foot Wagner grade 1-4; 3) The number of ulcers 1-2, if there are 2 ulcers, select the one with serious condition as the observation object, requiring the ulcer wound to be measurable, and the ulcer area is ^1-10cm2 ; 4) Those who agree to participate in this clinical trial and sign the written informed consent patient.

2 sample size This trial plans to enroll 24 patients with diabetic foot, among them, subjects S0104 and S0212 withdraw.

3 treatment options Study Medication: After routine cleaning of the wound surface, the wound surface was cleaned with normal saline. Apply the ointment of Example 3 on the sterile dressing with a thickness of about 2 mm. The medicine is required to completely cover the wound, and then the dressing is covered on the wound and wrapped appropriately with gauze. The dressing was changed once a day for two weeks before the administration, and once every two days for the next two weeks. The researcher can adjust the frequency of dressing changes according to the specific condition of the patient until the wound is completely healed or the course of treatment is over. The course of treatment in this study was 28 days.

4 Curative effect index 1) The complete wound healing rate on the 14th and 28th day of administration; 2) The change rate of the wound area on the 14th and 28th day of administration compared with the baseline; 3) The percentage of subjects whose wound area was reduced by 50% or more compared with the baseline on the 14th and 28th day of administration; 4) Changes in the pain VAS score on the 14th and 28th day of administration compared with the baseline.

5 Curative effect analysis 5.1 Wound healing analysis The complete wound healing rate on the 14th day and the 28th day of administration; The change rate of the wound area on the 14th day and the 28th day of administration compared with the baseline; The percentage of subjects whose wound area was reduced by 50% or more compared with baseline on the 14th and 28th days of administration; Statistically describe the number of cases, mean value, standard deviation, minimum value, median value, maximum value, etc. on the 14th day and the 28th day of administration. If the wound on the 14th day of administration was completely healed and the wound area on the 28th day of administration was NA, the wound area on the 28th day of administration was regarded as 0 treatment. The Wilcoxon signed rank test was used to compare the differences in wound area before and after administration at each visit point, and the 95% confidence interval of the difference before and after administration was calculated. 5.2 Pain VAS Analysis Changes in pain VAS scores on day 14 and day 28 compared with baseline. Statistically describe the number of cases, mean value, standard deviation, minimum value, median value, maximum value, etc. on the 14th day and the 28th day of administration. If the VAS score on the 14th day of administration is 0 and NA on the 28th day of administration, the VAS score on the 28th day of administration is regarded as 0 treatment. The Wilcoxon signed rank test was used to compare the differences in VAS scores before and after administration at each visit point, and the 95% confidence interval of the difference before and after administration was calculated.

6 Results 1) Complete wound healing rate on the 14th and 28th days of administration The complete wound healing rate on the 14th day of administration was 16% (4 cases), and the wound healing rate on the 28th day of administration was 44% ( 4+7=11 cases, and 7 cases were completely healed on the 14th to 28th day of administration), see Table 1 for details, indicating that the possibility of complete wound healing at 28 days of administration is higher than that at 14 days of administration. Literature reports ("Wieman T J. Clinical efficacy of becaplermin (rhPDGF-BB) gel[J]. American Journal of Surgery, 1998, 176(2A Suppl): 74S", and "Ban Yijuan, Wang Aihong, Xu Zhangrong. Platelet-rich A randomized controlled study of gel in the treatment of refractory diabetic foot ulcers[J]. Chinese Journal of Diabetes, 2015, 000(005):306-310"), the complete wound healing rate of the placebo group/blank group was 0% within 14 days , the 14-day complete wound healing rate in this study was 16%, which was considered to be due to the efficacy of this product. Literature reports ("Wieman T J. Clinical efficacy of becaplermin (rhPDGF-BB) gel[J]. American Journal of Surgery, 1998, 176(2A Suppl): 74S", and "Ban Yijuan, Wang Aihong, Xu Zhangrong. Platelet-rich A randomized controlled study of gel in the treatment of refractory diabetic foot ulcers[J]. Chinese Journal of Diabetes, 2015, 000(005):306-310"), the complete wound healing rate of the placebo group/blank group at 28 days was 2- About 3%, the 28-day complete wound healing rate in this study was 44%, which is considered to be due to the efficacy of this product. ² ) The change rate of the wound area on the 14th ^day and the 28th day of administration compared with the baseline. It was 64.21% and 84.54%, showing that administration for 28 days has a better improvement effect than administration for 14 days. Literature reports (Li L, Chen D, Wang C, et al. Autologous platelet-rich gel for treatment of diabetic chronic refractory cutaneous ulcers: A prospective, randomized clinical trial. [J]. Wound Repair & Regeneration, 2015:495-505 ), the average reduction rates of the wound area on the 14th day and the 28th day compared with the baseline in the standard treatment group were 40% and 63% respectively. 64.21% and 84.54%, considered to be due to the efficacy of this product, see Table 2 for details. 3) The percentage of subjects whose wound area was reduced by 50% or more compared with the baseline on the 14th and 28th days of administration: The percentage of subjects whose wound area was reduced by 50% or more from the baseline on the 14th day of administration was 68.00% (17 cases), 84.00% on the 28th day of administration (17+4=21 cases, 4 cases of subjects with a reduction of 50% or more from the 14th to 28th day of administration), indicating the curative effect of 14 days of administration It is obvious, see Table 1 for details. 4) The significance of the change of wound area compared with the baseline: the average value of the baseline wound area was 2.77±2.90 cm ² , and the average wound area was 1.28±1.66 cm ² on the 14th day of administration. On the 14th day of administration, the average change of the wound area from the baseline was 1.66±2.27 cm ² , and the 95% confidence interval was (0.68, 2.65). For details, see Table 2-3. The p value of the normality test (Shapiro-Wilk) was <0.0001, indicating that the data did not obey the normal distribution, and the Wilcoxon signed rank test was used, and the p value was <0.0001, indicating that the difference between the wound area on the 14th day of administration and the baseline was statistically significant significance. Therefore, it can be considered that the Chinese medicinal composition of the test drug has a significant improvement effect on the wound area of the diabetic foot after the 14th day of administration. On the 28th day of administration, the average wound area was 0.59±1.06 cm ² . On the 28th day of administration, the mean change of the wound area from the baseline was 2.36±2.55 cm ² , and the 95% confidence interval was (1.26, 3.46). See Table 2-3 for details. Compared with the 14th day of administration, the mean change was larger , the wound area is reduced even more. The p value of the normality test (Shapiro-Wilk) = 0.0002, indicating that the data does not obey the normal distribution, using the Wilcoxon signed rank test, the p value < 0.0001, indicating that the difference between the wound area on the 28th day of administration and the baseline is statistically significant significance. Therefore, it can be considered that the Chinese medicine composition of the test drug has a significant improvement effect on the wound area of the diabetic foot after 28 days of administration, and the improvement effect is better than that of 14 days of administration. 5) Changes of the pain VAS score on the 14th and 28th day of administration compared with the baseline: The mean value of the pain VAS score decrease from the baseline on the 14th day and the 28th day of administration was 1.39 and 2.09, respectively, and the mean decrease rate was 45.87 % and 74.32%, see Table 4 for details, indicating that the pain on the 28th day of administration was reduced more than that on the 14th day. 6) Significance of change in pain VAS score compared with baseline: The average baseline value of pain VAS score was 2.84±1.14, and the average pain VAS score was 1.52±0.86 on the 14th day of administration. On the 14th day of administration, the mean change in pain VAS score from baseline was 1.39±1.08, and the 95% confidence interval was (0.93, 1.86). See Table 5 for details. The p-value of the Wilcoxon signed rank test was <0.0001, indicating that the difference in VAS score on the 14th day of administration was statistically significant compared with the baseline. Therefore, it can be considered that the pain sensation of the test drug Chinese medicinal composition is significantly lower than that of the baseline after administration for 14 days. On the 28th day of administration, the average pain VAS score was 1.12±0.99. On the 28th day of drug administration, the mean change in pain VAS score compared with baseline was 2.09±1.06, and the 95% confidence interval was (1.62, 2.56). See Table 5 for details. Lighten even more. The p-value of the Wilcoxon signed-rank test was <0.0001, indicating that the difference in VAS score on the 28th day of administration was statistically significant compared with the baseline. Therefore, it can be considered that the pain sensation of the test drug and Chinese medicinal composition is significantly lower than that of the baseline in the 28th day of administration, and is more reduced than that of the 14th day of administration. 7) The comparison before and after treatment of this test example is shown in Figure 1.

In addition, the results showed that the ointment prepared from the traditional Chinese medicine compositions of Examples 1-2 and 4-10 had basically the same therapeutic effect on diabetic foot as the ointment of Example 3.

To sum up, the traditional Chinese medicine composition of the present invention has significant curative effect on wound healing of diabetic foot, and also has significant pain relief. Table 1: Healing rate of wound area 50% or more reduction from baseline in 14 days (number of people) Percentage (%) of subjects with 50% or more reduction from baseline at 14 days Complete recovery in 14 days (number of people) 14-day complete recovery rate (%) 50% or more reduction from baseline in 28 days (number of people) Percentage of subjects with 50% or more reduction from baseline at 28 days (%) Complete recovery in 28 days (number of people) 28-day complete recovery rate (%) 15 60.00 4 16.00 twenty one 84.00 11 44.00 Table 2: Changes in the wound area of each subject Subject screening number Baseline wound area (cm ² ) Wound area on the 14th day (cm ² ) Baseline - Day 14 (cm ² ) Change from baseline on day 14 (%) Wound area on day 28 (cm ² ) Baseline - Day 28 (cm ² ) Change from baseline on day 28 (%) 14-day reduction from baseline by 50% or more 14 days to achieve complete healing 50% or more reduction from baseline in 28 days 28 days to achieve complete healing S0101 2.36 0.71 1.65 69.92 0.69 1.67 70.76 yes no yes no S0102 0.75 0.16 0.59 78.67 0.07 0.68 90.67 yes no yes no S0103 4.71 2.36 2.35 49.89 1.41 3.30 70.06 no no yes no S0104 0.95 . . . . . . . . . . S0201 7.85 5.65 2.20 28.03 3.53 4.32 55.03 no no yes no S0202 0.47 0 0.47 100 0 0.47 100 yes yes yes yes S0203 0.71 0.24 0.47 66.20 0 0.71 100 yes no yes yes S0204 0.71 0.42 0.29 40.85 0.42 0.29 40.85 no no no no S0205 1.18 0 1.18 100 0 1.18 100 yes yes yes yes S0206 0.39 0.13 0.26 66.67 0.09 0.30 76.92 yes no yes no S0207 2.51 1.65 0.86 34.26 0.59 1.92 76.49 no no yes no S0208 9.81 2.94 6.87 70.03 1.73 8.08 82.36 yes no yes no S0209 4.71 4.40 0.31 6.58 3.67 1.04 22.08 no no no no S0210 0.63 0 0.63 100 0 0.63 100 yes yes yes yes S0211 9.75 0 9.75 100 0 9.75 100 yes yes yes yes S0212 0.53 . . . . . . . . . . S0213 5.65 3.93 1.72 30.44 0 5.65 100 no no yes yes S0214 3.14 1.26 1.88 59.87 0 3.14 100 yes no yes yes S0215 1.51 0.08 1.43 94.70 0 1.51 100 yes no yes yes S0216 2.54 2.54 0 0 0 2.54 100 no no yes yes S0217 4.71 2.36 2.35 49.89 0.79 3.92 83.23 no no yes no S0218 0.31 0.08 0.23 74.19 0 0.31 100 yes no yes yes S0219 0.24 0.02 0.22 91.67 0.01 0.23 95.83 yes no yes no S0220 0.79 0.12 0.67 84.81 0 0.79 100 yes no yes yes S0221 2.36 0.47 1.89 80.08 0.47 1.89 80.08 yes no yes no N (Missing) 25(0) 23(2) 23(2) 23(2) 23(2) 23(2) 23(2) 23(2) 23(2) 23(2) 23(2) Min 0.24 0 0 0 0 0.23 22.08 \ \ \ \ Max 9.81 5.65 9.75 100 3.67 9.75 100 \ \ \ \ Medium 1.51 0.42 0.86 69.92 0.01 1.51 95.83 \ \ \ \ Q1 0.71 0.08 0.31 40.85 0 0.63 76.49 \ \ \ \ Q3 4.71 2.36 1.89 91.67 0.69 3.30 100 \ \ \ \ mean 2.77 1.28 1.66 64.21 0.59 2.36 84.54 \ \ \ \ SD 2.90 1.66 2.27 29.87 1.06 2.55 21.35 \ \ \ \ Table 3: Statistical test of wound area change Mean±SD Testing method Statistics p-value Degree of certainty% Change from baseline on day 14 (cm ² ) 1.66±2.27 95% confidence interval (0.68, 2.65) 93.90 normality test Statistics W=0.6351 p-value<0.0001 Wilcoxon signed rank test Statistics S=126.5 p-value<0.0001 Change from baseline on day 28 (cm ² ) 2.36±2.55 95% confidence interval (1.26, 3.46) 99.34 normality test Statistics W=0.7882 p-value = 0.0002 Wilcoxon signed rank test Statistics S=138 p-value<0.0001 Table 4: Changes in VAS scores of subjects Subject screening number Baseline VAS score Day 14 VAS score Baseline - Day 14 Change from baseline on day 14 (%) Day 28 VAS score Baseline - Day 28 Change from baseline on day 28 (%) S0101 3 2 1 33.33 2 1 33.33 S0102 3 0 3 100 0 3 100 S0103 3 1 2 66.67 1 2 66.67 S0104 2 . . . . . . S0201 4 2 2 50.00 2 2 50.00 S0202 2 1 1 50.00 . . . S0203 1 1 0 0 0 1 100 S0204 2 1 1 50.00 1 1 50.00 S0205 2 0 2 100 0 2 100 S0206 2 1 1 50.00 1 1 50.00 S0207 4 3 1 25.00 2 2 50.00 S0208 5 4 1 20.00 2 3 60.00 S0209 4 3 1 25.00 3 1 25.00 S0210 4 0 4 100 0 4 100 S0211 3 0 3 100 0 3 100 S0212 2 . . . . . . S0213 3 3 0 0 0 3 100 S0214 5 2 3 60.00 0 5 100 S0215 2 1 1 50.00 0 2 100 S0216 2 2 0 0 0 2 100 S0217 4 3 1 25.00 2 2 50.00 S0218 1 1 0 0 0 1 100 S0219 2 1 1 50.00 1 1 50.00 S0220 2 1 1 50.00 0 2 100 S0221 4 2 2 50.00 2 2 50.00 N (Missing) 25(0) 23(2) 23(2) 23(2) 22(3) 22(3) 22(3) Min 1 0 0 0 0 1 25.00 Max 5 4 4 100 3 5 100 Medium 3 1 1 50.00 0.5 2 83.33 Q1 2 1 1 25.00 0 1 50.00 Q3 4 2 2 60.00 2 3 100 mean 2.84 1.52 1.39 45.87 0.86 2.09 74.32 SD 1.14 1.12 1.08 32.36 0.99 1.06 27.40 Note: The wound surface was completely healed after 14 days of administration of S0202, and the medication was stopped, and this case was regarded as a completed case. Table 5: Statistical Tests for Changes in Pain VAS Scores Mean±SD Testing method Statistics p-value Degree of certainty% Change from baseline on day 14 1.39±1.08 95% confidence interval (0.93, 1.86) 99.99 normality test Statistics W=0.8691 p-value = 0.0062 Wilcoxon signed rank test Statistics S=95 p-value<0.0001 Change from baseline on day 28 2.09±1.06 95% confidence interval (1.62, 2.56) 100 normality test Statistics W=0.8426 p-value = 0.0025 Wilcoxon signed rank test Statistics S= 126.5 p-value<0.0001

Experiment 2: Preliminary evaluation of the effectiveness and safety of traditional Chinese medicine composition in treating pressure sores

1 Selection criteria for qualified subjects 1.1 Diagnostic criteria Refer to the staging diagnostic criteria for stage II and III pressure ulcers in the "Quick Reference Guide for Prevention and Treatment of Pressure Ulcers" developed and implemented by the American Pressure Ulcer Advisory Committee, the European Pressure Ulcer Advisory Committee, and the Pan Pacific Pressure Injury Alliance in 2014. Stage II: Partial cortical loss Partial cortical loss presents as a superficial open ulcer with a pinkish-pink surface and no slough. Can also present as intact or open/ruptured serous blisters. Appearance is a clear or dry superficial ulcer without carrion and bruising (bruising suggests suspected deep tissue injury). Skin tears, injuries from medical tape, perineal dermatitis, macerated erosions, or exfoliation should not be described as stage II. Stage III: Whole-thickness loss Subcutaneous fat can be seen, but bones, tendons, and muscles are not exposed. Slough may be present but does not obscure the depth of tissue loss. Sinus tracts and undermining may occur. The depth of stage III pressure ulcers varies by anatomical location. There is no subcutaneous tissue on the bridge of the nose, ears, occiput, and ankle, and stage III pressure ulcers in these areas can be superficial. Conversely, fatty areas can develop into very deep stage III pressure sores. Bones and tendons are not visible or directly palpable. 1.2 Test case standard 1) Hospitalized patients with pressure sore stage II and III; 2) ≤2 wounds; 3) Age 18~75; 4) Voluntary treatment.

2 treatment options 2.1 Routine care 2.1.1 Holistic care Do a good job of basic nursing care for patients according to graded nursing standards to ensure that bed sheets and hospital gowns are clean, dry and smooth; it is recommended to use jet-type anti-pressure sore air mattress care to ensure that the air mattress is continuously inflated; establish a turning card and turn over every 2 to 4 hours depending on the condition ; Refer to the "Pressure Ulcer Prevention and Treatment Quick Reference Guide" to provide appropriate nutritional support for patients (assess the patient's nutritional status in a timely manner, provide adequate calories, protein, hydration, and vitamins and minerals); refer to the guidelines for different parts of the Pressure ulcers use different surfaces of support. Strengthen health education on pressure ulcer prevention and care for patients and their families. 2.1.2 Debridement care Fully expose the surface of the pressure sore, wash the sore surface and the skin around the sore surface with 0.9% normal saline according to the principle of aseptic operation (the washing area is 5 cm larger than the edge of the sore surface), and then wipe the sore surface with a cotton ball soaked in 0.9% normal saline And peri-wound skin, thoroughly remove carrion and secretions until the fresh sore base is fully exposed. After debridement, rinse the sore surface with 0.9% normal saline again. 2.2 Interventions 2.2.1 Test drug: the ointment of Example 3. Specifications: 25 g/bottle, batch number: 20160715, storage conditions: a cool and dry place. Production date: July 15, 2016, valid until July 14, 2018. 2.2.2 Medication method: firstly perform debridement and nursing, and then apply the ointment directly to the wound surface with a thickness of about 2 mm, bandage and fix it with sterile gauze for external use, and change the dressing every 2 days. Try to keep the dressing for 24 hours. If it falls off in the middle, wipe it with physiological saline and then temporarily cover the sore with sterile gauze. 2.2.3 Course of treatment: use the medicine until the sore surface is healed, if it has not healed after 50 days, the test will end.

3 observation items 3.1 Effectiveness Observation 1) Pain VAS score during dressing change; 2) Pressure Ulcer Healing Scale (PUSH) score; 3) The appearance time of new epithelium; 4) Sore surface healing time. Observation time points: PUSH scoring and photographing were performed on the sore surface before treatment and on the 10th, 30th, and 50th days of treatment. The sum of the 3 scores of sore surface area, sore surface exudate volume, and sore surface tissue type is the PUSH score result. The total score decreases as effective, the total score increases as deterioration, and the total score does not change as invalid. It is used for comprehensive evaluation of pressure ulcers Treatment of various stages of efficacy. The sore surface should be photographed before the treatment, on the 10th, 30th, and 50th days of the treatment (if the sore surface heals during the period, the photo will be taken after the healing), a total of 4 times. Before taking pictures, let the patient fully expose the sore surface, and at the same time, pay attention to protecting the privacy of the patient. Stick a photo label on the sore surface at the 6 o'clock direction of the sore surface taken. The label information includes: visit (V1, V2, V3, V4), initials, and date. 3.2 Safety observation 1) Vital signs: respiration, heart rate, blood pressure, body temperature, pulse. 2) Observation time points: before medication, on the 10th day after medication, and at the end of the experiment. 3) Local skin condition: 5 minutes after application, the researcher observes and inquires about the skin condition after topical application. If there is any discomfort such as burning sensation, pain, itching, etc., record it, and ask the family members of the subject to inform the responsible person in time if there is any discomfort nurse, who notified the study doctor. 4) Blood routine, liver and kidney function: before the drug, on the 10th day of the drug, and at the end of the test, check the laboratory indicators of the subject to preliminarily determine whether the test drug has adverse effects on the biochemical indicators of the subject, and to monitor the safety of the drug. initial evaluation. 5) Adverse events, serious adverse events: observe at any time.

4 Evaluation criteria 4.1 Curative effect evaluation index 1) Pain VAS score during dressing change; 2) Pressure Ulcer Healing Scale (PUSH) score; 3) The appearance time of new epithelium; 4) Sore surface healing time.

5 Safety Evaluation 5.1 Skin irritation: The researchers observed and asked about the skin condition after topical application for the first 5 minutes after application, and recorded if there was any discomfort such as burning sensation, pain, itching, etc. 5.2 Incidence of adverse events. 5.3 Incidence of serious adverse events.

6 Statistical Analysis 6.1 The description of quantitative indicators will calculate the number of cases, mean, standard deviation, median, minimum value, and maximum value. 6.2 The description of category and grade indicators uses the number of cases and percentages of each category. All statistical tests are two-sided tests, and a P value of less than or equal to 0.05 will be considered statistically significant (unless otherwise specified). For the analysis of various indicators at different time points before and after the intervention of pressure sore care, the method of variance analysis was used, and the evaluation of the curative effect at each time point was analyzed by paired t test. The independent sample t test was used to analyze the reduction of indicators at each time point between the two groups. 6.3 Safety Evaluation Analyze and describe the skin adverse reactions, adverse events, and serious adverse events that occurred.

7 Results 7.1 Enrollment of subjects and completion of observation 7.1.1 Enrollment of subjects This study plans to enroll 20 cases, and actually enrolls 20 cases. See Table 6 for details. Table 6: Enrollment and Drop-out of Cases, Exclusion of Cases Number of enrolled cases Number of dropped cases Number of excluded cases total 20 2 0 Reasons for dropped cases: 1 patient withdrew from the follow-up due to personal reasons, 1 patient withdrew due to repeated illness, and the remaining 18 patients completed the clinical study. The shedding rate was 10%. 7.2 Basic Information 7.1.1 General Information Table 7: General Information (n=20) project index Number of cases/value gender male 11 Female 9 age) Mean±SD 68.5±6.8 Min~Max 59~88 Pressure Ulcer Staging Phase II 13 Phase III 7 Number of wounds (pieces) 1 15 2 4 3 1 parts buttocks 17 ankle 2 sacrococcygeus 1 previous medication none 0 7.1.2 Disease baseline characteristics Table 8: Baseline scores of subjects before medication index Mean±SD Min m Max BradenScore 16.3±3.1 9 17 twenty one PUSH score 9.9±2.8 6 10 16 As can be seen from Table 6-8, there were 11 male subjects and 9 female subjects enrolled in this study, with an average age of 68.5 years, with the lowest age being 59 years old and the highest age being 88 years old. There were 13 cases of stage II pressure sores and 7 cases of stage III pressure sores; 15 cases had 1 wound, 4 cases had 2 wounds, and 1 case had 3 wounds; 17 cases had pressure sores on the buttocks, ankles 2 cases, 1 case in the sacrum. The median Braden score of all subjects was 17 points, the lowest score was 9 points, and the highest score was 21 points. 7.3 Efficacy and safety analysis 7.3.1 Disease efficacy analysis 1) Pain score 5 times before dressing change Table 9: Comparison of VAS scores 5 times before dressing change after treatment Mean±SD Min m Max f P 1 4.7±1.8 2 4 8 5.567 0.0005 2 4.0±2.0 2 3 8 3 3.2±1.9 0 3 6 4 2.8±1.9 0 2 6 5 2.1±1.6 0 2 6 In Table 9, one-way analysis of variance was used, F=31.4, P=0.0005, indicating that there were statistical differences in pain scores at different dressing change times. Using paired t-test for pairwise comparison, the VAS score at the second dressing change was significantly lower than that at the first dressing change (P=0.0015), and the VAS score at the fifth dressing change was also significantly lower than the first score ( P<0.0001). It can be seen from Table 9 that the pain situation during the first 5 dressing changes showed that the pain score gradually decreased each time the dressing was changed, and the pain level at the second dressing change (4.0±2.0) was higher than that at the first dressing change (4.7±1.8 ) decreased significantly (P=0.0015). At the third dressing change, the pain level had dropped from moderate pain to mild pain. At the fifth dressing change, the pain score had dropped to 2.1±1.6. 2) Pressure Ulcer Healing Scale (PUSH) Score Table 10: Comparison of PUSH scores before and after treatment Mean±SD Min m Max f P 0 days 9.9±2.8 6 10 16 19.31 <0.0001 10 days 7.6±3.3 2 7 15 30 days 4.2±3.6 1 4 12 50 days 1.3±3.2 0 0 10 In Table 10, one-way analysis of variance was used, F=19.31, P<0.0001, indicating that there were statistical differences in PUSH scores at different treatment times. Paired t-test was used for pairwise comparison. The PUSH score after the 10th day of treatment was significantly lower than the pre-treatment PUSH score (P=0.0004), and the PUSH score at the end of treatment was also significantly lower than the pre-treatment score (P<0.0001). It can be seen from Table 10 that the Pressure Ulcer Healing Scale (PUSH score) showed that with the progress of treatment, the PUSH score continued to decline, and the PUSH score after the 10th day of treatment (7.6±3.3) was significantly lower than the pre-treatment PUSH score (9.9±2.8 , P=0.0004), on the 50th day of treatment, the subject was basically cured (PUSH score=1.3±3.2). 3) Appearance time of neoepithelium Table 11: Appearance time of neoepithelium after treatment Mean±SD Min m Max neoepithelial appearance time 8.6±4.1 2 8.5 18 It can be seen from Table 11 that among the 20 subjects with stage II and III pressure ulcers in this pilot test, the median time for new epithelium to appear is about 8.5 days, with an average of 8.5±4.1 days. The median time of wound healing time was about 16 days, the average time was 17.2±11.7 days, and the wound healing rate was 65%. 4) Wound healing condition Table 12: Wound healing time after treatment Mean±SD Min m Max sore healing time 17.2±11.7 5 16 46 Table 13: Cases of wound healing after treatment (n=20) sores heal Number of cases percentage(%) have 13 65% none 7 35% 7.3.2 Safety Analysis None of the patients had skin irritation or other obvious discomfort. 7.4 See Figure 2 for the comparison before and after treatment of this test case. In addition, the results showed that the ointments prepared from the traditional Chinese medicine compositions of Examples 1-2 and 4-10 had basically the same therapeutic effect on pressure sores as the ointment of Example 3.

In summary, the traditional Chinese medicine composition of the present invention has a certain therapeutic effect on stage II and III pressure sores, can relieve pain, promote the healing of pressure sores and the formation of new epithelium, and no skin irritation and adverse reactions occurred during the observation period of the drug.

Test Example 3: Preliminary evaluation of the effectiveness and safety of traditional Chinese medicine composition in the treatment of venous ulcers of lower extremities

1 Subject selection and experimental design 1.1 Qualified subject selection criteria 1.1.1 Diagnostic criteria 1.1.1.1 The diagnostic criteria for venous ulcers of lower extremities were formulated with reference to "Clinical Vascular Surgery (5th Edition)" (2018 Edition). 1) It occurs mostly in the lower 1/3 of the calf (foot boot area), and is most common in the inner ankle. 2) Varicose veins and ankle edema are common in lower legs. 3) Venous ulcers generally manifest as irregular, painless ulcers with clear boundaries. When the inflammation is severe, venous rest pain may appear. Mainly distending pain, which can be relieved by raising the affected limb and resting in bed. 4) Yellow cellulose-like exudate can be seen on the ulcer surface, and the surrounding skin is erythema or pigmentation, and has different degrees of sclerosis (lipid sclerosis). 5) Auxiliary examination: Doppler ultrasonography, lower extremity venography, CT or MRI, laboratory examination (high-sensitivity C-reactive protein, prothrombin determination, homocysteine), etc. 1.1.2 Criteria for experimental cases 1.1.2.1 Criteria for inclusion of cases 1) Aged over 18 years old (including 18 years old), gender is not limited; 2) Patients who meet the diagnostic criteria for venous ulcers of lower extremities, according to the classification criteria of the American Society of Phlebology (CEAP), ulcers Grade C6, that is, skin changes caused by venous diseases and ongoing ulcers, and deep or mixed ulcers with a course of disease ≥ 30 days; 3) The area of a single ulcer is 4-25cm ² , if the subject meets the requirements in multiple places 4) Patients with ankle-brachial index (ABI) ≥ 0.8; patients who agreed to participate in this clinical trial and signed a written informed consent form. 1.1.2.2 Criteria for Excluding Cases 1) Arterial ulcers, traumatic ulcers, diabetic ulcers, malignant ulcers, rheumatic ulcers, neuropathic, vasculitic and hematological (such as sickle-shaped red blood cell) ulcers, ulcers with coagulation disorders , and those with drug-reactive ulcers; 2) Those with exposed bone, muscle (tendon) or fascia wound beds; 3) Those with allergic constitution and those who are allergic to the test drug or drug components; 4) Those who have participated in the study within the past 4 weeks Patients in other clinical trials; 5) Patients with severe cardiovascular, cerebrovascular, liver, kidney and hematopoietic system primary diseases; 6) Pregnant, breastfeeding women or those who have a birth plan within 6 months; 7) Researchers believe that it is not suitable to participate in this Other circumstances of the test. 1.1.2.3 Exit criteria (1) The researcher decides to withdraw 1) After the subject takes the drug, the ulcer area expands, or the condition worsens, and severe complications such as sepsis, toxic shock, pulmonary embolism, etc., require other treatment, Subjects may withdraw from the trial and receive other treatments at the investigator's discretion; 2) During the clinical trial, the subject has some comorbidities, complications or special physiological changes, and the investigator considers it inappropriate to continue the trial; 3) The subject's compliance is poor (compliance <80.00% or >120.00%), and the test drug is not used or interviewed as required; 4) The prohibited drug or other treatment specified in the protocol is used in the test, which affects the efficacy or safety judge. (2) The subject has the right to withdraw from the trial on his own. The subject has the right to withdraw from the trial, including the subject who explicitly withdraws from the trial and the subject who does not explicitly withdraw from the trial but no longer accepts medication and testing. Lost to follow-up also belongs to "Exit" (or "drop off"). The investigators should try their best to understand the reasons for the withdrawal of the subjects and record them, such as: the perceived efficacy is not good, some adverse reactions are intolerable, the clinical trial cannot be continued for some reason, economic factors, or unexplained reasons, etc. 1.1.3 Sample size: 20 patients were enrolled in this study. 1.2 Treatment plan The researcher disinfects the wound surface and the skin around the wound surface, removes necrotic self-tissue and purulent secretions, and after fully cleaning the wound surface, smears the ointment of Example 3 on the sterile dressing with a thickness of about 2mm. Cover the wound, then cover the wound with a dressing, wrap it appropriately with 4 layers of gauze, and apply moderate compression and binding. During the study period, the dressing was changed every 2-3 days, and the researcher performed the dressing change operation until the wound was completely healed or the course of treatment was over. The course of treatment in this study was 28 days. 1.3 Efficacy indicators (1) The change rate of the wound area on the 14th day and the 28th day of administration compared with the baseline; (2) The complete wound healing rate on the 14th day and the 28th day of administration; (3) The 14th day of administration and the percentage of subjects whose wound area decreased by 50% or more compared with the baseline on day 28; (4) Changes in pain VAS scores on day 14 and day 28 compared with baseline. 1.4 Safety indicators: Adverse events and serious adverse events after medication, focusing on local irritation at the medication site or systemic allergic reactions and other corresponding adverse reactions.

2 Statistical analysis methods 2.1 Wound healing: complete wound healing is based on "complete epithelialization of the wound without drainage" as the standard, each dressing change is evaluated once, and the complete wound healing rate and wound area comparison are counted on the 14th and 28th days of administration. Rate of change from baseline, percentage of subjects with a 50% or greater reduction in wound area from baseline. 1) Wound area (mm ² ) = long diameter of wound (mm) x short diameter of wound (mm) x π x 0.25. 2) Complete wound healing rate = (Number of wounds meeting the healing standard/Total number of qualified participants in the study) × 100%. 3) Change rate of wound area from baseline = (subject's wound area before treatment - subject's wound area after treatment) / subject's wound area before treatment × 100%. 4) The wound area in the screening period/baseline is the result recorded by photographing and recording before the first administration after the ulcer is cleaned up. 5) During the screening period/baseline, on the 14th day of administration and on the 28th day of administration (or the test is completed in advance), the wound surface needs to be photographed and recorded under the same irradiation conditions. 6) For continuous variables, the effective number of cases, mean, standard deviation, median, quartile, maximum value, minimum value, 95% CI, etc. are used to describe the detection value, and variance analysis is used to evaluate the curative effect before and after medication. 7) For discrete variables, chi-square test or Fisher's exact probability method was used to evaluate the curative effect before and after medication. 2.2 Pain VAS score: describe the degree of pain when changing the dressing in the baseline period, on the 14th day of administration, and on the 28th day of administration. 1) The Visual Analogue Scale/Score (VAS) was used for evaluation, and the subjects marked the corresponding scale on the line segment marked 0-100mm according to their own feelings to indicate the degree of pain. Among them, 0 means no pain, and 100 means unbearable severe pain. 2) Use the effective number of cases, mean, standard deviation, median, quartile, maximum value, minimum value, 95% CI, etc. to describe the detection value, and analyze the variance to evaluate the curative effect before and after medication.

3 Results A total of 20 subjects were enrolled in this trial, 1 subject voluntarily withdrew from the trial, 1 subject was lost to follow-up, and the remaining 18 subjects completed the trial according to the protocol requirements. 3.1 Wound healing: take pictures of the wounds of cases 1 and 2 during the screening period/baseline, on the 14th day of administration and on the 28th day of administration (or complete the test in advance), see Figures 3 and 4 for details. Among them, Figure 3 is the photo record of Case 1, and the pictures from left to right in Figure 3 are the wound pictures before use (2021.11.04), 14 days of use (2021.11.18) and 28 days of use (2021.12.02) ; Figure 4 is the photo record of Case 2. The pictures from left to right in Figure 4 are the wound pictures before use (2021.10.11) and 14 days after use (2021.10.25). See Table 14 for details on the changes in the wound area of each subject. Table 14: List of subjects' wound area changes Subject screening number Baseline area Wound area 14 days after treatment Wound area 28 days after treatment Change rate from baseline period to 14 days after treatment Change rate from baseline period to 28 days after treatment 01 25.9 12.3 12.3 52.51 52.51 02 13 4.2 3.1 67.69 76.15 03 3.4 1.2 0.9 64.71 73.53 04 4.2 1.9 1.1 54.76 73.81 05 3.8 1.5 1.5 60.53 60.53 06 4.7 5.9 0.2 -25.53 95.74 07 4.6 0 0 100.00 100.00 08 6.1 3 4 50.82 34.43 09-1 54.9 quit quit quit quit 09-2 11.5 quit quit quit quit 10 2.4 0.9 0 62.50 100.00 11 3.5 0.7 0 80.00 100.00 12 4.2 0.6 0.4 85.71 90.48 13 6.3 14.1 14.1 -123.81 -123.81 14-1 17.9 1.6 0.8 91.06 95.53 14-2 2.4 0 0 100.00 100.00 15 15.6 2.3 1 85.26 93.59 16 8.4 5.5 1.6 34.52 80.95 17-1 6.1 4.4 2.1 27.87 65.57 17-2 1.7 0 0 100.00 100.00 18 8.5 7.8 5.4 8.24 36.47 19 5.1 2.2 Lost to follow up 56.86 Lost to follow up 20 7.7 6.1 5.88 20.78 23.64 Note: Subject screening numbers 09-1 and 09-2 in Table 14 represent the two wounds on the body of subject No. 9; subject screening numbers 14-1 and 14-2 represent the The two wounds on the body of subject No. 17-1 and 17-2 respectively represent the two wounds on the body of subject No. 17.

As shown in Table 14, the average wound area in the baseline period, the 14th day and the 28th day after the administration were 9.65±11.446cm ² , 3.63±3.901cm ² and 2.72±4.004cm ² respectively. Moreover, through statistical calculation, it was found that the wound area decreased by 50.21% (95%CI: 26.84%, 73.58%) and 66.46% (95%CI: 42.63%, 90.28%) compared with the baseline on the 14th and 28th days after medication; On the 14th day after treatment, 3 (14.29%) wounds were completely healed, and on the 28th day after treatment, 5 (25.00%) wounds were completely healed. On the 14th day after treatment, 15 (71.43%) wounds had a 50% reduction in area compared with the baseline, and on the 28th day after treatment, 16 (80.00%) wounds had a 50% reduction in area from the baseline. Overall, most of the subjects tended to shrink the ulcer area after treatment, especially in the first 14 days after starting treatment, the wound healing was more significant, and after 14 days, the healing trend became slow. 3.2 Pain VAS score The VAS pain scores in the baseline period, 14 days after medication and 28 days after medication were 47.30±20.36, 27.16±19.10 and 18.47±21.77, respectively. The comparison results of the VAS pain scores in the baseline period, 14 days after medication, and 28 days after medication were statistically significant (P<0.05). Compared with the baseline period, the VAS score decreased by 42.24% (95%CI: 29.48%, 55.01%) 14 days after medication, and decreased by 63.85% (95%CI: 50.23%, 7.47%) 28 days after medication compared with the baseline period ), the change rate of VAS score 14 days after medication and 28 days after medication was statistically significant (P=0.0199). Overall, there was a trend toward less wound pain after treatment. In addition, the results showed that the ointments prepared from the traditional Chinese medicine compositions of Examples 1-2 and 4-10 had basically the same therapeutic effect on venous lower extremity ulcers as the ointment of Example 3.

To sum up, the traditional Chinese medicine composition of the present invention has the potential to reduce the area of venous ulcers of lower extremities and relieve wound pain, has a certain curative effect on the healing of venous ulcers of lower extremities, and is safe and easy to use.

In this specification, the schematic representations of the above terms are not necessarily directed to the same embodiment or example. Furthermore, the described specific features, structures, materials or characteristics may be combined in any suitable manner in any one or more embodiments or examples. In addition, those skilled in the art to which the present invention pertains can combine and combine different embodiments or examples and features of different embodiments or examples described in this specification without conflicting with each other.

Although the embodiments of the present invention have been shown and described above, it can be understood that the above embodiments are exemplary and should not be construed as limitations of the present invention. Variations, modifications, substitutions and variations can be made to the above-described embodiments.

none

The above and/or additional aspects and advantages of the present invention will become apparent and comprehensible from the description of the embodiments in conjunction with the following drawings, wherein: Fig. 1 is the contrast figure before and after treatment of diabetic foot in the present invention's test example 1; Fig. 2 is the comparison chart before and after treatment of pressure sore in Test Example 2 of the present invention; Fig. 3 is the comparative figure before and after treatment of case 1 venous ulcer in test example 3 of the present invention; Fig. 4 is a comparison chart before and after treatment of venous ulcer in Case 2 in Test Example 3 of the present invention.

Claims (10)

A use of a traditional Chinese medicine composition in the preparation of medicines. The medicine is used to prevent or treat chronic skin ulcers. The traditional Chinese medicine composition includes the following raw materials in parts by weight: 8-30 parts of Coptidis rhizome, 6-25 parts of Burnet elata, and 20 parts of kunzhi oil -50 parts, 4-18 parts of angelica, 5-20 parts of beeswax, and 1-5 parts of borneol. The use as described in Claim 1, characterized in that the drug is used to prevent or treat chronic skin ulcers with a course of disease ≥ 30 days; Optionally, the drug is used to promote wound healing of chronic skin ulcer and/or relieve pain; Optionally, the drug is used to promote new epithelialization of chronic skin ulcer wounds or reduce the formation of scars; Optionally, the dosage form of the drug includes at least one of ointment, cream, oil and patch; Optionally, the dosage form of the drug is selected from ointment; Optionally, the route of administration of the drug is selected from smearing; Optionally, the thickness of the smear is 1-3mm. A method for preventing or treating chronic skin ulcers, comprising: administering a Chinese medicinal composition to a subject, the Chinese medicinal composition comprising the following raw materials in parts by weight: 8-30 parts of coptis, 6-25 parts of Burnet, 20-50 parts of kunzhi oil, 4-18 parts of angelica, 5-20 parts of beeswax, and 1-5 parts of borneol. The method according to claim 3, wherein the traditional Chinese medicine composition is used to prevent or treat chronic skin ulcers with a course of disease ≥ 30 days; Optionally, the traditional Chinese medicine composition is used to promote wound healing of chronic skin ulcer and/or relieve pain; Optionally, the traditional Chinese medicine composition is used to promote new epithelialization of chronic skin ulcer wounds or reduce the formation of scars; Optionally, the dosage form of the traditional Chinese medicine composition includes at least one of ointment, cream, oil and patch; Optionally, the dosage form of the traditional Chinese medicine composition is selected from ointment; Optionally, the route of administration of the traditional Chinese medicine composition is selected from daubing; Optionally, the thickness of the smear is 1-3mm. The use as described in any one of claim items 1-2 or the method described in any one of claim items 3-4, wherein the chronic skin ulcers include diabetic skin ulcers, pressure sore ulcers, venous ulcers, At least one of insufficient ulcers; Optionally, the chronic skin ulcer is selected from deep layer or mixed ulcer; Optionally, the single ulcer area of the chronic skin ulcer is 1-40cm ² ; Optionally, the The diabetic skin ulcers include diabetic foot or diabetic bed sores; Optionally, the pressure sore ulcers include stage II pressure sores or stage III pressure sores; Optionally, the pressure sore ulcers include partial-thickness loss or full-thickness Deletion, preferably, the pressure sore ulcer is selected from superficial stage III pressure ulcers occurring on the bridge of the nose, ears, occiput and/or ankle; or, the pressure sore ulcer is selected from fatty multiple areas and is deep Stage III pressure ulcers; Optionally, the venous ulcers include venous lower extremity ulcers; Optionally, the venous lower extremity ulcers are selected from patients with lower extremity venous ulcers with an ankle-brachial index (ABI) ≥ 0.8. The use or method according to any one of claim items 1-5, wherein the Chinese medicine composition comprises the following raw materials in parts by weight: 10-18 parts of coptis, 7-13 parts of Burnet, 21-38 parts of kunzhi oil, 4-9 parts of angelica, 5-12 parts of beeswax, and 1-2 parts of borneol; Optionally, the traditional Chinese medicine composition includes the following raw materials in parts by weight: 12-15 parts of coptis, 10-12 parts of Burnet, 28-32 parts of kunzhi oil, 6-8 parts of angelica, 7-9 parts of beeswax, and 1.2-1.8 parts of borneol. The use or method according to any one of claims 1-6, characterized in that the Chinese medicine composition further includes 27-65 parts by weight of pharmaceutically acceptable excipients, preferably 40-55 parts by weight. The use or method according to claim 7, wherein the auxiliary material includes at least one of an oily base, a water-soluble base, and an emulsion base; Optionally, the auxiliary material is selected from vegetable oil; Optionally, the vegetable oils include olive oil, soybean oil, greenthorn oil, flaxseed oil, sunflower oil, jojoba oil, peanut oil, tea oil, tea tree oil, rosehip oil, argan oil, avocado oil , castor oil, sesame oil, salad oil, corn germ oil and corn oil at least one. The use or method according to any one of claim items 1-8, wherein the traditional Chinese medicine composition comprises the following preparation steps: (1) Extracting the Angelica sinensis, collecting the medicinal residues I, water extract, volatile oil and saturated aqueous solution for subsequent use; (2) decocting the Coptidis rhizome, Burnet and medicinal dregs I, and concentrating the collected filtrate and the water extract to obtain a thick paste; (3) Mix the volatile oil, saturated aqueous solution, thick paste, and borneol to obtain a reserve liquid; (4) Mix the kunzhi oil, beeswax and stock solution to obtain the traditional Chinese medicine composition. The use or method according to claim 9, characterized in that in step (2), the number of times of decoction is 1-3 times, and the decoction time is 1-3 hours; Optionally, step (2) further includes: Carrying out the first decocting treatment of the Coptis Rhizoma and Burnet burnet, and obtaining the filtrate I and medicinal residues II after the first filtration treatment; Mixing the medicinal residues II and the medicinal residues I for a second decoction treatment, and a second filtration treatment to obtain filtrate II; The filtrate I, filtrate II and water extract are mixed and concentrated into a clear paste; Carrying out alcohol precipitation treatment to the clear paste, and concentrating the obtained filtrate III under reduced pressure after the third filtration treatment to obtain a thick paste; Optionally, the solvent used in the alcohol precipitation treatment is 70-100% ethanol solution, and the alcohol precipitation treatment reaches an ethanol concentration of 40-60%; Optionally, the third filtration treatment includes heat filtration and/or heat preservation treatment; Optionally, the precipitate obtained after the thermal filtration treatment is washed with aqueous ethanol, and a filtrate is obtained after filtration, and the filtrate is combined with the thermal filtrate obtained by the thermal filtration treatment to obtain the filtrate III; Optionally, the temperature of the hot filtration is 60°C-85°C, and the washing treatment is performed with 40-50% ethanol; Optionally, the first decocting treatment is carried out twice, each decocting time is 1-1.5h; Optionally, the time of the second decocting treatment is 1-1.5h; Optionally, the relative density of the clear paste at 40°C-50°C is 1.02-1.15, and the relative density of the thick paste at 40°C-50°C is 1.10-1.25; Optionally, the step (4) further includes heating and co-melting the kunlin oil and beeswax, mixing them uniformly, and then performing cooling treatment, and mixing the obtained mixed solution with the standby solution to obtain the traditional Chinese medicine composition; Optionally, the adjuvant is mixed with the quinoa oil and beeswax; Optionally, the temperature of the cooling treatment is 30°C-75°C.

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