A traditional Chinese medicine composition for treating diabetic foot and a preparation method thereof

Abstract

The present application relates to the field of traditional Chinese medicine, and particularly relates to a traditional Chinese medicine composition for treating diabetic foot and a preparation method thereof.The traditional Chinese medicine composition is made of the following weight parts of traditional Chinese medicine raw materials: 180-220 parts of raw astragalus, 140-160 parts of angelica, 90-120 parts of dogwood, 180-220 parts of coptis, 180-220 parts of scrophulariaceae, 90-120 parts of atractylodes, 90-120 parts of cortex phellodendri, 40-60 parts of white yam, 40-60 parts of pearl powder, 40-60 parts of geum japonicum and 4-8 parts of artificial musk.The traditional Chinese medicine composition has the effects of benefiting qi and nourishing blood, nourishing yin and purging fire, clearing heat and drying dampness, promoting blood circulation and generating muscle, and has a good therapeutic effect on foot ulcer caused by diabetes.Moreover, the traditional Chinese medicine composition is safe and effective for long-term use, and the patient is not prone to recurrence.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine technology, and in particular to a traditional Chinese medicine composition for treating diabetic foot and its preparation method. Background Technology

[0002] Diabetic foot (DF) is a complication of diabetes caused by distal neuropathy and vascular disease in the lower extremities, resulting in foot infection, ulceration, and deep tissue destruction. It is characterized by high morbidity, high disability rate, and high mortality rate.

[0003] The direct causes of diabetic foot include distal lower extremity neuropathy, varying degrees of vascular disease and infection, and are related to loss of sensation in the foot, poor circulation, foot deformities, irritation (such as friction or pressure), trauma, and the duration of diabetes. Compared with ordinary trauma, diabetic foot is characterized by a high risk of infection, poor healing ability, and high recurrence rate. Because the early onset of diabetic foot is insidious and clinical manifestations are not obvious, patients often lack awareness of diabetic foot, leading to delayed diagnosis and treatment, increased treatment difficulty and cost, and making diabetic foot one of the most common reasons for hospitalization among diabetic patients. Diabetic foot has a rapid onset, rapid progression, and is difficult to treat, leading to foot ulcers, infections, and gangrene, severely impacting patients' quality of life, increasing their suffering, and potentially causing amputation or even death, placing a huge economic and social burden on patients, families, and society. Therefore, finding scientific and effective drugs for the treatment of diabetic foot is of great significance for improving ulcer healing rates, reducing amputation and mortality rates, and alleviating the medical burden.

[0004] Currently, diabetic foot treatment mainly involves blood sugar control, improved circulation, anti-infection, local wound management, wound repair and decompression, and surgery. Basic treatment includes regulating and controlling blood sugar using hypoglycemic drugs (such as metformin and insulin) to reduce the risk of vascular damage; using vasodilators (such as cilostazol and sargrelate hydrochloride), antiplatelet drugs (such as aspirin and clopidogrel), anticoagulants (such as rivaroxaban), neurotrophic drugs (such as mecobalamin), or hyperbaric oxygen therapy to correct local hypoxia and promote lower limb blood circulation; targeted antibiotic treatment for wound infection control or dressing changes; and interventional or surgical treatment in severe cases. These treatments are mostly symptomatic and cannot improve the wound environment, and are prone to drug resistance, resulting in less than ideal treatment outcomes, high recurrence rates, long treatment courses, and high costs for some treatment methods.

[0005] Compared to the single-mechanism treatment of Western medicine, traditional Chinese medicine (TCM) has the advantage of acting simultaneously on multiple targets and pathways. Diabetic foot falls under the category of "gangrene" in TCM research. Currently, TCM generally believes that its pathogenesis is related to the interaction of "dampness, pathogenic factors, and blood stasis," namely, "due to deficiency, pathogenic factors lead to blood stasis, which obstructs the body's vital energy, causing putrefaction and damage." Diabetes falls under the category of "wasting and thirsting syndrome" in TCM. Studies have shown that the underlying cause of diabetes is prolonged wasting and thirsting syndrome leading to deficiency of Qi and Yin. Qi deficiency weakens the body's ability to transport fluids and blood to the extremities, and combined with Yin deficiency and insufficient fluids, this results in insufficient Qi, blood, essence, and fluids in the extremities, depriving the tendons and vessels of nourishment. The pathogenesis of diabetic gangrene of the extremities is most closely related to "pathogenic factors" (dampness, heat, and toxins), with "insufficient vital energy and deficiency of both Qi and Yin" as the root cause, and "stasis of Qi and blood, obstruction of collaterals, and excessive damp-heat and fire toxins" as the manifestations. The disease location is in the tendons, vessels, blood, and muscles, exhibiting the characteristics of deficiency in the root and excess in the manifestations. In summary, diabetic foot is mainly caused by "prolonged thirst, deficiency of both qi and yin, excess of pathogenic factors, stagnation of qi and blood, and obstruction of meridians," leading to malnourishment of the extremities, poor blood supply to the ulcer surface, difficulty in removing necrotic tissue, and difficulty in the formation of new granulation tissue, ultimately resulting in chronic and intractable ulcers. Therefore, traditional Chinese medicine (TCM) treatment of diabetic foot emphasizes both internal and external treatment, with the main approach being to invigorate blood circulation and remove blood stasis, improve blood supply to the foot; clear heat and dampness, and eliminate stagnation to create an environment conducive to healing; tonify the middle jiao and replenish qi, regulate immunity and nourish nerves; and eliminate pathogenic factors while supporting the body's resistance, providing overall conditioning.

[0006] The Wagner classification is a classic method for assessing the severity of diabetic foot ulcers, ranging from 0 to 5. It guides clinical intervention based on lesion depth, extent of infection, and degree of necrosis. A higher classification indicates a more severe condition and a greater risk of amputation. Grade 0 (High-risk foot): No open ulcers on the foot, but high-risk factors such as neuropathy (e.g., decreased sensation, foot deformity) or vascular disease (e.g., pale skin, coldness) are present; Grade 1 (Superficial ulcer): Ulcers only involve the epidermis or dermis, the wound is clean and uninfected, commonly found at pressure points on the sole of the foot; Grade 2 (Deep ulcer): Ulcers extend to tendons, joint capsules, or periosteum, possibly accompanied by soft tissue infection (e.g., cellulitis), but without abscess or osteomyelitis; Grade 3 (Deep infection): Ulcers complicated by deep abscesses, osteomyelitis, or joint infection, with significant bone destruction, and patients may experience systemic symptoms such as fever; Grade 4 (Localized gangrene): Localized gangrene occurs in the toes or forefoot, with tissue ischemia and necrosis, and clear boundaries; Grade 5 (Total foot gangrene): Most or all of the entire foot is necrotic, often accompanied by sepsis, endangering life.

[0007] Currently, among existing traditional Chinese medicine treatments for diabetic foot ulcers, only Xiangleitang Foot Ointment (containing 2.5mg of senna extract and 10mg of total glycosides of Centella asiatica per gram) is approved. However, the National Medical Products Administration only approves it for wounds with a cross-sectional area of ​​less than 25cm² after debridement. 2"Wagner grade 1 diabetic foot ulcers." Whether using ancient prescriptions or modern Chinese medicine, there are currently no clinically available treatments for higher-grade ulcers (Wagner grade 2 and above). Furthermore, these medications are expensive, placing a heavy financial burden on patients and limiting their choices. Therefore, researching novel Chinese medicine products with better therapeutic effects, fewer side effects, lower recurrence rates, and the ability to treat higher-grade ulcers is of great significance. Summary of the Invention

[0008] The purpose of this invention is to overcome the shortcomings of existing drugs for treating diabetic foot, such as poor therapeutic effect, high recurrence rate and large toxic side effects, and to provide a traditional Chinese medicine composition for treating diabetic foot that invigorates qi and nourishes yin, promotes blood circulation and tissue regeneration, and its preparation method.

[0009] Traditional Chinese medicine (TCM) views diabetic foot as having both external and internal causes. External causes include damp-heat and fire toxins damaging the collaterals, leading to blood stasis, poor blood flow, and necrosis of peripheral tissues. Internal causes include insufficient vital energy (Qi) and deficiency of both Qi and Yin, which prevents the elimination of damp-heat toxins, resulting in the accumulation of harmful metabolic products (especially glucose metabolites) and damage to microvessels. Therefore, the root cause of diabetic foot is "insufficient vital energy and deficiency of both Qi and Yin," while the symptoms are "blood stasis, collateral obstruction, and excessive damp-heat and fire toxins."

[0010] The formulation of the composition of the present invention is based on the following approach: (1) Tonifying drugs are used to replenish vital energy, including Astragalus membranaceus and Cornus officinalis; (2) Heat-clearing and dampness-removing drugs are used to remove damp-heat and fire toxins, including Coptis chinensis, Scutellaria baicalensis, Atractylodes lancea and Phellodendron chinense; (3) Blood-activating drugs are used to activate blood circulation, remove blood stasis, and clear microvessels, including Angelica sinensis, Lithospermum erythrorhizon and artificial musk; (4) In addition, for the symptoms of skin ulceration in diabetic foot, tissue-regenerating drugs are used to promote wound healing, including Ampelopsis japonica and pearl powder.

[0011] On one hand, the present invention provides a traditional Chinese medicine composition for treating diabetic foot, made from the following traditional Chinese medicine raw materials in parts by weight:

[0012] Raw Astragalus membranaceus 175-260 parts, Angelica sinensis 130-170 parts, Cornus officinalis 75-125 parts, Coptis chinensis 175-260 parts, Scutellaria baicalensis 175-260 parts, Atractylodes lancea 75-125 parts, Phellodendron chinense 75-125 parts, Ampelopsis japonica 20-70 parts, pearl powder 20-70 parts, Lithospermum erythrorhizon 20-70 parts, and artificial musk 2-10 parts.

[0013] Preferably, the traditional Chinese medicine composition for treating diabetic foot of the present invention is made from the following parts by weight of traditional Chinese medicine raw materials:

[0014] Raw Astragalus membranaceus 180-220 parts, Angelica sinensis 140-160 parts, Cornus officinalis 90-120 parts, Coptis chinensis 180-220 parts, Scutellaria baicalensis 180-220 parts, Atractylodes lancea 90-120 parts, Phellodendron chinense 90-120 parts, Ampelopsis japonica 40-60 parts, pearl powder 40-60 parts, Lithospermum erythrorhizon 40-60 parts, and artificial musk 4-8 ​​parts.

[0015] Preferably, the traditional Chinese medicine composition for treating diabetic foot of the present invention is made from the following parts by weight of traditional Chinese medicine raw materials:

[0016] 220 parts raw Astragalus membranaceus, 160 parts Angelica sinensis, 110 parts Cornus officinalis, 180 parts Coptis chinensis, 200 parts Scutellaria baicalensis, 90 parts Atractylodes lancea, 120 parts Phellodendron chinense, 40 parts Ampelopsis japonica, 60 parts pearl powder, 40 parts Lithospermum erythrorhizon, and 8 parts artificial musk.

[0017] Preferably, the traditional Chinese medicine composition for treating diabetic foot of the present invention is made from the following parts by weight of traditional Chinese medicine raw materials:

[0018] 200 parts raw Astragalus membranaceus, 150 parts Angelica sinensis, 100 parts Cornus officinalis, 200 parts Coptis chinensis, 200 parts Scutellaria baicalensis, 100 parts Atractylodes lancea, 100 parts Phellodendron chinense, 50 parts Ampelopsis japonica, 50 parts pearl powder, 50 parts Lithospermum erythrorhizon, and 5 parts artificial musk.

[0019] Preferably, the traditional Chinese medicine composition for treating diabetic foot of the present invention is made from the following parts by weight of traditional Chinese medicine raw materials:

[0020] 200 parts raw Astragalus membranaceus, 140 parts Angelica sinensis, 90 parts Cornus officinalis, 220 parts Coptis chinensis, 180 parts Scutellaria baicalensis, 110 parts Atractylodes lancea, 100 parts Phellodendron chinense, 60 parts Ampelopsis japonica, 60 parts pearl powder, 60 parts Lithospermum erythrorhizon, and 6 parts artificial musk.

[0021] On the other hand, the present invention provides a method for preparing the above-mentioned traditional Chinese medicine composition for treating diabetic foot, comprising the following steps:

[0022] Take raw Astragalus membranaceus, Angelica sinensis, and Cornus officinalis separately, add 8-20 times the amount of water, soak for 30-60 minutes, heat and reflux to extract 1-3 times, reflux for 1-3 hours each time, filter, combine the extracts and concentrate to a first concentrated paste with a relative density of 1.10-1.25. Take the first concentrated paste, dry under reduced pressure at 60℃-80℃ and pulverize to obtain the first dry paste. Take Coptis chinensis, Scutellaria baicalensis, Atractylodes lancea, Phellodendron chinense, Ampelopsis japonica, and Lithospermum erythrorhizon, percolate to extract with 60%-95% ethanol, collect 10-30 times the amount of percolate, recover the ethanol under reduced pressure, concentrate to a second concentrated paste with a relative density of 1.10-1.25, take the second concentrated paste, dry under reduced pressure at 60℃-80℃ and pulverize to obtain the second dry paste. Combine the first and second dry pastes, then add pearl powder and artificial musk and mix well to obtain the final product.

[0023] Alternatively, combine raw Astragalus membranaceus, Angelica sinensis, Cornus officinalis, Coptis chinensis, Scutellaria baicalensis, Atractylodes lancea, Phellodendron chinense, Ampelopsis japonica, and Lithospermum erythrorhizon, and extract with 60%-95% ethanol percolation. Collect 10-30 times the amount of percolation, recover the ethanol under reduced pressure, and concentrate to a relative density of 1.10-1.25 to obtain a concentrated paste. Dry the concentrated paste under reduced pressure at 60℃-80℃ to obtain a dry paste, pulverize it, and set it aside. Add pearl powder and artificial musk to the above dry paste, mix well, and you have the final product.

[0024] Alternatively, combine raw Astragalus membranaceus, Angelica sinensis, Cornus officinalis, Coptis chinensis, Scutellaria baicalensis, Atractylodes lancea, Phellodendron chinense, Ampelopsis japonica, and Lithospermum erythrorhizon, add 8-20 times the amount of water, soak for 30-60 minutes, heat and reflux to extract 1-3 times, reflux for 1-3 hours each time, filter, combine the extracts and concentrate to a concentrated paste with a relative density of 1.10-1.25, take the concentrated paste, dry under reduced pressure at 60℃-80℃ and pulverize to obtain a dry paste; add pearl powder and artificial musk to the above dry paste and mix well to obtain the final product.

[0025] Preferably, the preparation method of the traditional Chinese medicine composition for treating diabetic foot according to the present invention includes the following steps:

[0026] Take raw Astragalus membranaceus, Angelica sinensis, and Cornus officinalis, add 8 times the amount of water, soak for 30 minutes, heat and reflux twice, reflux for 1 hour each time, filter, combine the extracts and concentrate to a first concentrated paste with a relative density of 1.10. Take the first concentrated paste, dry under reduced pressure at 70℃ and pulverize to obtain the first dry paste. Take Coptis chinensis, Scutellaria baicalensis, Atractylodes lancea, Phellodendron chinense, Ampelopsis japonica, and Lithospermum erythrorhizon, percolate and extract with 70% ethanol, collect 15 times the amount of percolate, recover the ethanol under reduced pressure, concentrate to a second concentrated paste with a relative density of 1.10, take the second concentrated paste, dry under reduced pressure at 70℃ and pulverize to obtain the second dry paste. Combine the first and second dry pastes, then add pearl powder and artificial musk and mix well to obtain the final product.

[0027] Alternatively, combine raw Astragalus membranaceus, Angelica sinensis, Cornus officinalis, Coptis chinensis, Scutellaria baicalensis, Atractylodes lancea, Phellodendron chinense, Ampelopsis japonica, and Lithospermum erythrorhizon, and extract with 70% ethanol percolation. Collect 15 times the amount of percolate, recover the ethanol under reduced pressure, and concentrate to a relative density of 1.10 to obtain a concentrated extract. Dry the concentrated extract under reduced pressure at 70°C to obtain a dry extract, pulverize it, and set it aside. Add pearl powder and artificial musk to the above dry extract, mix well, and you have the final product.

[0028] Alternatively, combine raw Astragalus membranaceus, Angelica sinensis, Cornus officinalis, Coptis chinensis, Scutellaria baicalensis, Atractylodes lancea, Phellodendron chinense, Ampelopsis japonica, and Lithospermum erythrorhizon, add 8 times the amount of water, soak for 30 minutes, heat and reflux twice, reflux for 1 hour each time, combine the extracts, filter, combine the decoctions, concentrate the filtrate to a concentrated paste with a relative density of 1.10, take the concentrated paste, dry under reduced pressure at 70℃, and pulverize to obtain a dry paste; add pearl powder and artificial musk to the above dry paste, mix well, and you have the final product.

[0029] On the other hand, the above-mentioned traditional Chinese medicine composition for treating diabetic foot provided by the present invention can be formulated into any pharmaceutically acceptable external dosage form; the dosage form is selected from ointments, emulsions, gels, solutions, powders, lotions, oils or tinctures; ointments are preferred.

[0030] The topical dosage form is prepared using conventional methods in the pharmaceutical field, and pharmaceutically acceptable excipients may be added if necessary. These pharmaceutically acceptable excipients are selected from sesame oil, petrolatum, lanolin, glycerin, and polyethylene glycol. Sesame oil is preferred.

[0031] On the other hand, the present invention provides the use of the above-mentioned traditional Chinese medicine composition in the preparation of a medicament for treating diabetic foot.

[0032] Preferably, the diabetic foot is Wagner grade 2 or higher.

[0033] Preferably, the drug promotes ulcer healing and promotes angiogenesis.

[0034] To facilitate a better understanding of this invention, the effects of each ingredient are explained below:

[0035] Astragalus is the dried root of *Astragalus membranaceus* (Fisch.) Bge. var. *mongholicus* (Bge.) Hsiao or *Astragalus membranaceus* (Fisch.) Bge., belonging to the legume family. It is harvested in spring and autumn, with the fibrous roots and root head removed before sun-drying. It has a sweet taste and slightly warm properties. It enters the lung and spleen meridians. Its functions include tonifying qi and raising yang, consolidating the exterior and stopping sweating, promoting diuresis and reducing swelling, generating fluids and nourishing blood, promoting circulation and relieving pain, promoting pus drainage and detoxification, and promoting wound healing and tissue regeneration. It is used for qi deficiency and fatigue, poor appetite and loose stools, sinking of middle qi, chronic diarrhea and rectal prolapse, hematochezia and metrorrhagia, spontaneous sweating due to exterior deficiency, edema due to qi deficiency, internal heat and thirst, anemia and chlorosis, hemiplegia, numbness and pain, carbuncles that are difficult to heal, and chronic ulcers that do not heal.

[0036] Angelica sinensis is the dried root of Angelica sinensis (Oliv.) Diels, a plant belonging to the Apiaceae family. It is harvested in late autumn, with the fibrous roots and soil removed. After the moisture has partially evaporated, it is bundled into small bunches, placed on a shed, and slowly dried by smoking; alternatively, it can be sun-dried or dried at low temperature. It has a sweet and pungent taste and is warm in nature. It enters the liver, heart, and spleen meridians. It has the effects of nourishing blood and promoting blood circulation, regulating menstruation and relieving pain, and moistening the intestines and promoting bowel movements. It is used for blood deficiency and chlorosis, dizziness and palpitations, irregular menstruation, amenorrhea and dysmenorrhea, abdominal pain due to deficiency and cold, rheumatic pain, traumatic injuries, carbuncles and sores, and constipation due to intestinal dryness.

[0037] Cornus officinalis (Shanzhuyu) is the dried, ripe pulp of the plant Cornus officinalis Sieb. et Zucc., belonging to the Cornaceae family. The fruit is harvested in late autumn or early winter when the peel turns red. It is then dried over a low heat or briefly blanched in boiling water, after which the pits are promptly removed. It has a sour and astringent taste and is slightly warm in nature. It enters the liver and kidney meridians. It has the effects of tonifying the liver and kidneys, and astringing and consolidating the body. It is used for dizziness and tinnitus, lower back and knee pain, impotence and seminal emission, enuresis and frequent urination, metrorrhagia and leukorrhea, profuse sweating and collapse, and internal heat and thirst.

[0038] Coptis chinensis is the dried rhizome of *Coptis chinensis* Franch., *Coptis deltoidea* C.Y. Chenget Hsiao, or *Coptis yunnanensis* Wall., all belonging to the Ranunculaceae family. These three are commonly known as "Weilian," "Yalian," and "Yunlian," respectively. It is harvested in autumn, the fibrous roots and soil are removed, it is dried, and any remaining fibrous roots are removed by knocking. It is bitter and cold in nature. It enters the heart, spleen, stomach, liver, gallbladder, and large intestine meridians. It has the effects of clearing heat and drying dampness, purging fire and detoxifying. It is used for damp-heat fullness, vomiting and acid regurgitation, diarrhea, jaundice, high fever and delirium, excessive heart fire, restlessness and insomnia, palpitations, hematemesis due to blood heat, red eyes, toothache, thirst, carbuncles and boils; externally, it is used to treat eczema, damp sores, and ear discharge.

[0039] Scutellaria baicalensis Georgi, a plant in the Lamiaceae family, is a dried root. It is harvested in spring and autumn, with the fibrous roots and soil removed. After sun-drying, the outer bark is removed by pounding, and then it is completely dried. It has a bitter taste and is cold in nature. It enters the lung, gallbladder, spleen, large intestine, and small intestine meridians. It has the effects of clearing heat and drying dampness, purging fire and detoxifying, stopping bleeding, and calming the fetus. It is used for damp-heat syndrome, summer-heat syndrome, chest tightness and nausea, damp-heat fullness, diarrhea, jaundice, lung-heat cough, high fever and thirst, hematemesis due to blood heat, carbuncles and boils, and threatened abortion.

[0040] Atractylodes lancea (Thunb.) DC. or Atractylodes chinensis (DC.) Koidz., belonging to the Asteraceae family, is a dried rhizome. It is harvested in spring and autumn, cleaned of dirt and sand, sun-dried, and the fibrous roots removed. It has a pungent and bitter taste, and is warm in nature. It enters the spleen, stomach, and liver meridians. It has the effects of drying dampness and strengthening the spleen, dispelling wind and cold, and improving eyesight. It is used for dampness obstructing the middle jiao, abdominal distension, diarrhea, edema, beriberi, rheumatic pain, colds due to wind-cold, night blindness, and blurred vision.

[0041] Phellodendron bark is the dried bark of the Phellodendron chinense Schneid., a plant in the Rutaceae family. It is commonly known as "Sichuan Phellodendron." After peeling the bark, the outer bark is removed, and it is sun-dried. It has a bitter taste and is cold in nature. It enters the kidney and bladder meridians. It has the effects of clearing heat and drying dampness, purging fire and eliminating steaming heat, and detoxifying and healing sores. It is used for damp-heat diarrhea, jaundice with dark urine, leukorrhea and vulvar itching, painful urination due to heat, beriberi with weakness and paralysis, bone steaming fever, night sweats, seminal emission, sores and carbuncles, eczema and damp sores.

[0042] Bai Lian is the dried tuberous root of *Ampelopsis japonica* (Thunb.) Makino, a plant in the Vitaceae family. It is harvested in spring and autumn, after which mud, sand, and fine roots are removed, and the roots are cut into longitudinal or oblique slices and sun-dried. It has a bitter taste and is slightly cold in nature. It enters the Heart and Stomach meridians. It has the effects of clearing heat and detoxifying, reducing swelling and dissipating nodules, and promoting tissue regeneration. It is used for carbuncles, boils, scrofula, and burns.

[0043] Pearls are formed in bivalves such as the pearl oyster Pinctadafucata (Dunker), the mussel Hyriopsiscumingii (Lea), or the pleated crown mussel Cristariaplicata (Leach) when stimulated. They are removed from the shell, washed, and dried. Pearl powder is made by grinding clean pearls into a fine powder using the water-milling method. It has a sweet and salty taste and is cold in nature. It enters the heart and liver meridians. It has the effects of calming the mind and relieving fright, improving eyesight and clearing away pterygium, detoxifying and promoting tissue regeneration, and moisturizing the skin and removing blemishes. It is used for palpitations and insomnia, infantile convulsions and epilepsy, red and pterygium-related eye diseases, slow-healing sores, and skin pigmentation.

[0044] Lithospermum erythrorhizon is the dried root of *Arnebiaeuchroma* (Royle) Johnst. or *Arnebiaguttata* Bunge, both belonging to the Boraginaceae family. It is harvested in spring and autumn, cleaned of dirt and sand, and then dried. It has a sweet and salty taste and is cold in nature. It enters the heart and liver meridians. It has the effects of clearing heat and cooling blood, promoting blood circulation and detoxifying, and promoting rash eruption and eliminating spots. It is used for blood heat and toxicity, purplish-black rashes, incomplete measles eruption, sores, eczema, and burns.

[0045] Musk is the dried secretion from the musk sac of mature male musk deer (Moschus berezovskii Flerov, Moschrysogaster Hodgson, or Moschus moschiferus Linnaeus). Wild musk deer are hunted primarily from winter to the following spring. After capture, the musk sac is removed and dried in the shade, commonly known as "hairy musk." The sac is opened, the shell removed, and the remaining musk is called "musk kernel." Domestic musk deer have the musk kernel directly extracted from their sacs and dried in the shade or in a sealed desiccator. It has a pungent taste and warm properties. It enters the heart and spleen meridians. It has the effects of opening the orifices and waking the mind, promoting blood circulation and regulating menstruation, reducing swelling and relieving pain. It is used for febrile delirium, stroke with phlegm syncope, sudden syncope due to qi stagnation, coma due to sudden illness, amenorrhea, abdominal masses, difficult labor and stillbirth, chest pain, sudden abdominal pain, traumatic injuries, numbness and pain, carbuncles and scrofula, and sore throat. Artificial musk is used in the same formulation as natural musk.

[0046] The beneficial effects are as follows: The traditional Chinese medicine composition provided by this invention consists of raw Astragalus membranaceus, Angelica sinensis, Cornus officinalis, Coptis chinensis, Scutellaria baicalensis, Atractylodes lancea, Phellodendron chinense, Ampelopsis japonica, pearl powder, Lithospermum erythrorhizon, and artificial musk. In the above-mentioned traditional Chinese medicine composition, raw Astragalus membranaceus greatly replenishes the Qi of the spleen and lungs, nourishes the source of blood production, provides an energy basis for wound healing, and can also promote the elimination of toxins and pus, promote tissue regeneration and wound healing, promote the expulsion of deep toxins, and strengthen muscles and bones; Angelica sinensis nourishes blood and regulates Qi, so that Qi is vigorous and blood is generated, which can both replenish the depleted Yin and blood and promote local blood circulation; the two together are the principal herbs, solving the fundamental problem of "deficiency of Qi and blood and promotion of tissue regeneration", so that Qi and blood are abundant to nourish the wound. Cornus officinalis plays a unique and important role in this formula. It tonifies the liver and kidneys, astringes and consolidates, and nourishes yin. On the one hand, it assists Astragalus membranaceus and Angelica sinensis in tonifying essence and blood (the liver stores blood, and the kidneys store essence); on the other hand, its astringent properties prevent excessive depletion of qi, blood, and essence, making it specifically effective for chronic illnesses with yin deficiency or slow-healing sores. Furthermore, its use with bitter and cold herbs prevents damage to yin and depletion of vital energy, reflecting the profound consideration of "eliminating pathogens without harming the body's vital energy." The combined use of Scutellaria baicalensis, Coptis chinensis, and Phellodendron chinense has a strong effect in clearing heat and drying dampness, purging fire and detoxifying, and quenching thirst, effectively addressing the redness, swelling, and heat of sores. The symptoms of "intense heat and toxicity" or "damp-heat and fire toxicity," such as ulceration and pus discharge, are directly cleared of pathogenic factors and putrefaction, causing necrotic tissue to slough off. In conjunction with other Chinese medicines, it promotes the growth of granulation tissue and wound healing. Atractylodes lancea is aromatic and dispersing, dries dampness and strengthens the spleen. Since pus discharge from sores is often related to dampness, Atractylodes lancea can dry dampness and reduce pus discharge. At the same time, it strengthens the spleen to assist Astragalus membranaceus in replenishing qi and Angelica sinensis in promoting blood circulation. Its pungent and warm properties compensate for the bitter and cold nature of other medicines. Ampelopsis japonica clears heat and detoxifies, eliminates carbuncles and dissipates nodules, directly targeting carbuncles and sores to promote healing. The above six herbs are the assistant herbs. Purple gromwell root cools the blood, promotes blood circulation, detoxifies, and relieves rashes. It is especially effective in clearing heat toxins from the blood, and is highly effective for sores that are purple, red, swollen, and burning due to heat entering the blood. It also promotes local blood circulation. Pearl powder has the effects of astringing and promoting tissue regeneration, clearing heat and detoxifying, and calming the nerves. It can absorb exudate from wounds, keep the wound relatively dry, and promote the growth of granulation tissue and epithelial cells, accelerating wound healing. It can be used in the later stages of sores, for wounds that have not healed for a long time or ulcers, and is an excellent product for promoting tissue regeneration and wound closure. The above two herbs are used as adjuvant herbs. Artificial musk promotes blood circulation, unblocks meridians, reduces swelling, and relieves pain. As an adjuvant herb, its pungent and penetrating power is extremely strong, and it can penetrate the skin to guide other herbs directly to the affected area. It also promotes local blood circulation, tissue repair, and regeneration. For diabetic foot, the "blockage" and stagnation caused by vascular blockage and nerve numbness are due to the blood stasis of musk. The combined effects of these herbs include invigorating qi and nourishing blood, nourishing yin and purging fire, clearing heat and drying dampness, removing necrotic tissue and promoting tissue regeneration. They improve the body's ischemia and hypoxia, promote tissue growth and healing, and are used to treat diabetic foot syndrome in traditional Chinese medicine, which is characterized by qi and blood stagnation and damp-heat toxicity.

[0047] The present invention has the following beneficial effects:

[0048] The traditional Chinese medicine composition provided by this invention consists of raw Astragalus membranaceus, Angelica sinensis, Cornus officinalis, Coptis chinensis, Scutellaria baicalensis, Atractylodes lancea, Phellodendron chinense, Ampelopsis japonica, pearl powder, Lithospermum erythrorhizon, and artificial musk. In the above-mentioned traditional Chinese medicine composition, raw Astragalus membranaceus greatly tonifies the Qi of the spleen and lungs, nourishes the source of blood production, provides the energy basis for wound healing, and can also promote the drainage of pus, promote tissue regeneration and wound healing, promote the expulsion of deep toxins, and strengthen muscles and bones; Angelica sinensis nourishes blood and regulates Qi, so that Qi is vigorous and blood is generated, which can not only replenish the depleted Yin and blood, but also promote local blood circulation; the two together are the principal herbs, solving the fundamental problem of "deficiency of Qi and blood, and promotion of tissue regeneration", so that Qi and blood are abundant to nourish the wound. Cornus officinalis plays a unique and important role in this formula. It tonifies the liver and kidneys, astringes and consolidates, and nourishes yin. On the one hand, it assists Astragalus membranaceus and Angelica sinensis in tonifying essence and blood (the liver stores blood, and the kidneys store essence); on the other hand, its astringent properties prevent excessive depletion of qi, blood, and essence, making it specifically effective for chronic illnesses with yin deficiency or slow-healing sores. Furthermore, its use with bitter and cold herbs prevents damage to yin and depletion of vital energy, reflecting the profound consideration of "eliminating pathogens without harming the body's vital energy." The combined use of Scutellaria baicalensis, Coptis chinensis, and Phellodendron chinense has a strong effect in clearing heat and drying dampness, purging fire and detoxifying, and quenching thirst, effectively addressing the redness, swelling, and heat of sores. The symptoms of "intense heat and toxicity" or "damp-heat and fire toxicity," such as ulceration and pus discharge, are directly cleared of pathogenic factors and putrefaction, causing necrotic tissue to slough off. In conjunction with other Chinese medicines, it promotes the growth of granulation tissue and wound healing. Atractylodes lancea is aromatic and dispersing, dries dampness and strengthens the spleen. Since pus discharge from sores is often related to dampness, Atractylodes lancea can dry dampness and reduce pus discharge. At the same time, it strengthens the spleen to assist Astragalus membranaceus in replenishing qi and Angelica sinensis in promoting blood circulation. Its pungent and warm properties compensate for the bitter and cold nature of other medicines. Ampelopsis japonica clears heat and detoxifies, eliminates carbuncles and dissipates nodules, directly targeting carbuncles and sores to promote healing. The above six herbs are the assistant herbs. Purple gromwell root cools the blood, promotes blood circulation, detoxifies, and relieves rashes. It is especially effective in clearing heat toxins from the blood, and is highly effective for sores that are purple, red, swollen, and burning due to heat entering the blood. It also promotes local blood circulation. Pearl powder has the effects of astringing and promoting tissue regeneration, clearing heat and detoxifying, and calming the nerves. It can absorb exudate from wounds, keep the wound relatively dry, and promote the growth of granulation tissue and epithelial cells, accelerating wound healing. It can be used in the later stages of sores, for wounds that have not healed for a long time or ulcers, and is an excellent product for promoting tissue regeneration and wound closure. The above two herbs are used as adjuvant herbs. Artificial musk promotes blood circulation, unblocks meridians, reduces swelling, and relieves pain. As an adjuvant herb, its pungent and penetrating power is extremely strong, and it can penetrate the skin to guide other herbs directly to the affected area. It also promotes local blood circulation, tissue repair, and regeneration. For diabetic foot, the "blockage" and stagnation caused by vascular blockage and nerve numbness are due to the blood stasis of musk. The combined effects of these herbs include invigorating qi and nourishing blood, nourishing yin and purging fire, clearing heat and drying dampness, removing necrotic tissue and promoting tissue regeneration. They improve the body's ischemia and hypoxia, promote tissue growth and healing, and are used to treat diabetic foot syndrome in traditional Chinese medicine, which is characterized by qi and blood stagnation and damp-heat toxicity.

[0049] Compared to existing drugs that can only be used for Wagner grade 1 diabetic foot ulcers, the prescription of this invention can be used for Wagner grade 3 patients. Clinical cases show that it has a good healing effect on ulcers that penetrate subcutaneous fat to fascia and muscle, as well as soft or hard scabs with black lesions lacking blood supply. It also has good safety and no toxic side effects with long-term use. Attached Figure Description

[0050] Figure 1 The images show the skin of the rat paws and back of the herbal compositions prepared according to different embodiments of the present invention. Part A is the control group; Part B is the model group; Part C is the 0.06g crude drug / foot group of Example 1; Part D is the 0.17g crude drug / foot group of Example 1; Part E is the 0.06g crude drug / foot group of Example 2; Part F is the 0.17g crude drug / foot group of Example 2; Part G is the 0.06g crude drug / foot group of Example 3; Part H is the 0.17g crude drug / foot group of Example 3; and Part I is the 0.1g crude drug / foot group of Example 3.

[0051] Figure 2 The angiogenesis status of the full formula group and each of the separate formula groups.

[0052] Figure 3 A photo of the affected area before treatment for a diabetic foot patient.

[0053] Figure 4 Photo of a patient with diabetic foot who has had a wound cleaned and treated with traditional Chinese medicine.

[0054] Figure 5 Photo of the affected area on the 14th day of treatment for a diabetic foot patient.

[0055] Figure 6 Photo of the affected area on the 30th day of treatment for a diabetic foot patient.

[0056] Figure 7 Photo of the affected area on the 60th day of treatment for a diabetic foot patient.

[0057] Figure 8 The images show the before and after treatment results for diabetic foot patients. Part A shows the affected area before treatment; Part B shows the affected area on day 7 of treatment; Part C shows the affected area on day 14 of treatment; Part D shows the affected area on day 28 of treatment; Part E shows the affected area on day 42 of treatment; and Part F shows the affected area on day 42 of treatment.

[0058] Figure 9 The images show the before and after treatment results for diabetic foot patients. Part A shows the affected area before treatment, and Part B shows the affected area after treatment. Detailed Implementation

[0059] The present invention will be further described in detail through the following embodiments, but the scope of protection of the present invention is not limited to any specific embodiments. Other embodiments obtained by those skilled in the art based on the embodiments described in the embodiments, and in conjunction with the experimental design of traditional Chinese medicine compound prescriptions, without inventive effort, are all within the scope of protection of the present invention.

[0060] Example 1: A traditional Chinese medicine composition for treating diabetic foot 1

[0061] Made from the following ingredients in parts by weight: 200 parts raw Astragalus membranaceus, 150 parts Angelica sinensis, 100 parts Cornus officinalis, 200 parts Coptis chinensis, 200 parts Scutellaria baicalensis, 100 parts Atractylodes lancea, 100 parts Phellodendron chinense, 50 parts Ampelopsis japonica, 50 parts pearl powder, 50 parts Lithospermum erythrorhizon, and 5 parts artificial musk.

[0062] The preparation method of the above-mentioned traditional Chinese medicine composition for treating diabetic foot includes the following steps:

[0063] Take raw Astragalus membranaceus, Angelica sinensis, and Cornus officinalis, add 8 times the amount of water, soak for 30 minutes, heat and reflux twice, reflux for 1 hour each time, combine the extracts, filter, combine the decoctions, concentrate the filtrate to a relative density of 1.10 to obtain a concentrated paste, take the concentrated paste and dry under reduced pressure at 70℃ to obtain a dry paste, pulverize and set aside for use as dry paste 1; take Coptis chinensis, Scutellaria baicalensis, Atractylodes lancea, Phellodendron chinense, Ampelopsis japonica, and Lithospermum erythrorhizon, percolate extract with 70% ethanol, collect 15 times the amount of percolate, recover the ethanol under reduced pressure, concentrate to a relative density of 1.10 to obtain a concentrated paste, take the concentrated paste and dry under reduced pressure at 70℃ to obtain a dry paste, pulverize and set aside for use as dry paste 2; add pearl powder and artificial musk to dry paste 1 and dry paste 2, add sesame oil and mix well, which is the sample of extraction example 1, the yield is calculated by dividing the weight of the finished product by the weight of the medicinal materials, which is 37.22%.

[0064] Example 2: Traditional Chinese Medicine Composition for Treating Diabetic Foot

[0065] Made from the following ingredients in parts by weight: 200 parts raw Astragalus membranaceus, 150 parts Angelica sinensis, 100 parts Cornus officinalis, 200 parts Coptis chinensis, 200 parts Scutellaria baicalensis, 100 parts Atractylodes lancea, 100 parts Phellodendron chinense, 50 parts Ampelopsis japonica, 50 parts pearl powder, 50 parts Lithospermum erythrorhizon, and 5 parts artificial musk.

[0066] The preparation method of the above-mentioned traditional Chinese medicine composition for treating diabetic foot includes the following steps:

[0067] Raw Astragalus membranaceus, Angelica sinensis, Cornus officinalis, Coptis chinensis, Scutellaria baicalensis, Atractylodes lancea, Phellodendron chinense, Ampelopsis japonica, and Lithospermum erythrorhizon were combined and extracted by percolation with 70% ethanol. 15 times the amount of percolate was collected, and the ethanol was recovered under reduced pressure. The extract was concentrated to a relative density of 1.10 to obtain a concentrated paste. The concentrated paste was dried under reduced pressure at 70°C to obtain a dry paste, which was then pulverized for later use. Pearl powder and artificial musk were added to the above dry paste, and sesame oil was added and mixed well to obtain the sample of Extraction Example 2, with a yield of 33.97%.

[0068] Example 3: A traditional Chinese medicine composition for treating diabetic foot 3

[0069] Made from the following ingredients in parts by weight: 200 parts raw Astragalus membranaceus, 150 parts Angelica sinensis, 100 parts Cornus officinalis, 200 parts Coptis chinensis, 200 parts Scutellaria baicalensis, 100 parts Atractylodes lancea, 100 parts Phellodendron chinense, 50 parts Ampelopsis japonica, 50 parts pearl powder, 50 parts Lithospermum erythrorhizon, and 5 parts artificial musk.

[0070] The preparation method of the above-mentioned traditional Chinese medicine composition for treating diabetic foot includes the following steps:

[0071] Combine raw Astragalus membranaceus, Angelica sinensis, Cornus officinalis, Coptis chinensis, Scutellaria baicalensis, Atractylodes lancea, Phellodendron chinense, Ampelopsis japonica, and Lithospermum erythrorhizon, add 8 times the amount of water, soak for 30 minutes, heat and reflux twice, reflux for 1 hour each time, combine the extracts, filter, combine the decoctions, concentrate the filtrate to a relative density of 1.10 to obtain a concentrated paste, take the concentrated paste and dry it under reduced pressure at 70℃ to obtain a dry paste, pulverize it for later use; add pearl powder and artificial musk to the above dry paste, add sesame oil and mix well, which is the sample of extraction Example 3, with a yield of 44.53%.

[0072] Example 4: A traditional Chinese medicine composition for treating diabetic foot 4

[0073] It is made from the following raw materials in parts by weight: 220 parts raw Astragalus membranaceus, 160 parts Angelica sinensis, 110 parts Cornus officinalis, 180 parts Coptis chinensis, 200 parts Scutellaria baicalensis, 90 parts Atractylodes lancea, 120 parts Phellodendron chinense, 40 parts Ampelopsis japonica, 60 parts pearl powder, 40 parts Lithospermum erythrorhizon, and 8 parts artificial musk.

[0074] The preparation method of the above-mentioned traditional Chinese medicine composition for treating diabetic foot includes the following steps:

[0075] Combine raw Astragalus membranaceus, Angelica sinensis, Cornus officinalis, Coptis chinensis, Scutellaria baicalensis, Atractylodes lancea, Phellodendron chinense, Ampelopsis japonica, and Lithospermum erythrorhizon, add 10 times the amount of water, do not soak, and immediately heat and reflux twice, each time for 1.5 hours. Combine the extracts, filter, combine the decoctions, and concentrate the filtrate to a relative density of 1.20 to obtain a concentrated paste. Take the concentrated paste and dry it under reduced pressure at 60°C to obtain a dry paste, which is then pulverized for later use. Add pearl powder and artificial musk to the above dry paste, add sesame oil and mix well to obtain the sample of Extraction Example 4, with a yield of 46.72%.

[0076] Example 5: A traditional Chinese medicine composition for treating diabetic foot 5

[0077] It is made from the following ingredients in parts by weight: 200 parts raw Astragalus membranaceus, 140 parts Angelica sinensis, 90 parts Cornus officinalis, 220 parts Coptis chinensis, 180 parts Scutellaria baicalensis, 110 parts Atractylodes lancea, 100 parts Phellodendron chinense, 60 parts Ampelopsis japonica, 60 parts pearl powder, 60 parts Lithospermum erythrorhizon, and 6 parts artificial musk.

[0078] The preparation method of the above-mentioned traditional Chinese medicine composition for treating diabetic foot includes the following steps:

[0079] Raw Astragalus membranaceus, Angelica sinensis, Cornus officinalis, Coptis chinensis, Scutellaria baicalensis, Atractylodes lancea, Phellodendron chinense, Ampelopsis japonica, and Lithospermum erythrorhizon were combined and extracted by percolation with 70% ethanol. 15 times the amount of percolate was collected, and the ethanol was recovered under reduced pressure. The mixture was concentrated to a relative density of 1.15 to obtain a concentrated extract. The concentrated extract was dried under reduced pressure at 70°C to obtain a dry extract, which was then pulverized for later use. Pearl powder and artificial musk were added to the above dry extract, and sesame oil was added and mixed well to obtain the sample of Example 5, with a yield of 39.31%.

[0080] Example 6: Detection of the active ingredient in the compositions of Examples 1-3

[0081] (1) Baicalin: Determined by high performance liquid chromatography (General Chapter 0512, Part IV, Chinese Pharmacopoeia 2025). Chromatographic conditions and system suitability test: Octadecylsilane-bonded silica gel was used as the stationary phase; methanol-water-phosphoric acid (47:53:0.2) was used as the mobile phase; the detection wavelength was 280 nm. The theoretical plate number, calculated based on the baicalin peak, should not be less than 5000.

[0082] Preparation of the reference solution: Accurately weigh an appropriate amount of baicalin reference standard, add methanol to prepare a solution containing 50 μg per ml. Preparation of the test solution: Accurately measure 0.2 g of this product, place it in a 50 ml volumetric flask, add an appropriate amount of 70% methanol, sonicate for 30 min, cool, add 70% methanol to the mark, shake well, filter, and collect the filtrate.

[0083] Determination method: Accurately pipette 10 μl each of the reference solution and the test solution into the liquid chromatograph and determine the result.

[0084] (2) Berberine hydrochloride: Determined by high performance liquid chromatography (General Chapter 0512, Part IV, Chinese Pharmacopoeia 2025). Chromatographic conditions and system suitability test: Octadecylsilane-bonded silica gel was used as the stationary phase; acetonitrile-0.1% phosphoric acid solution (40:60) (with 0.1 g sodium dodecyl sulfonate per 100 ml) was used as the mobile phase; the detection wavelength was 265 nm. The theoretical plate number, calculated based on the berberine hydrochloride peak, should not be less than 5000. Preparation of the reference solution: Accurately weigh an appropriate amount of berberine hydrochloride reference standard, add methanol to prepare a solution containing 90 μg per ml.

[0085] Preparation of the test solution: Accurately measure 0.2 g of this product and place it in a 50 ml volumetric flask. Add an appropriate amount of methanol:hydrochloric acid (100:1) mixed solution, sonicate for 30 min, cool, add methanol:hydrochloric acid (100:1) mixed solution to the mark, shake well, filter, accurately pipette 5 ml of the filtrate into a 10 ml volumetric flask, add methanol:hydrochloric acid (100:1) mixed solution to the mark, shake well, filter, and take the filtrate to obtain the test solution.

[0086] Determination method: Accurately pipette 10 μl each of the reference solution and the test solution into the liquid chromatograph and determine the result.

[0087] (3) Astragaloside A: Determined by high performance liquid chromatography (General Chapter 0512, Part IV, Chinese Pharmacopoeia 2025). Chromatographic conditions and system suitability test: Octadecylsilane-bonded silica gel as the packing material; acetonitrile-water (32:68) as the mobile phase; evaporative light detector gain 50; gas pressure 40 psi; nebulizer mode heating 10%; drift tube 60℃. The theoretical plate number calculated based on the astragaloside A peak should be no less than 5000.

[0088] Preparation of reference solution: Take an appropriate amount of astragaloside A reference standard, accurately weigh it, and add methanol to prepare a solution containing 0.5 mg per ml.

[0089] Preparation of the test solution: Accurately measure 4g of this product, add 50ml of water, sonicate for 15min, and extract 5 times with 50ml of water-saturated n-butanol each time; separate the n-butanol layer, wash 3 times with ammonia solution each time with 60ml, discard the washings, and evaporate the n-butanol solution to dryness; dissolve the residue in 80% methanol and transfer it to a 10ml volumetric flask, dilute to the mark with 80% methanol, shake well, filter, and take the filtrate to obtain the test solution.

[0090] Determination method: Accurately pipette 5 and 10 μl of the reference solution and the test solution respectively, inject them into the liquid chromatograph, and determine the result.

[0091] Each experiment was conducted in three parallel tests, and the average value of the data was taken. The specific results are shown in Table 1.

[0092] Table 1: Results of determination of effective component content in the traditional Chinese medicine compositions of Examples 1-3

[0093] The results in Table 1 show that different preparation processes can effectively extract the active ingredients, with Example 3 showing the best extraction effect.

[0094] Example 7: The therapeutic effect of the composition of the present invention on streptozotocin-induced diabetic rat paw ulcers.

[0095] Model making:

[0096] Ninety healthy male SD rats were selected. After acclimatization, 10 rats were randomly selected from each weight group as the normal control group, and the rest were used for modeling. Before modeling, the rats were fasted for 24 hours but allowed free access to water. On the day of modeling, rats were intraperitoneally injected with 2% streptozotocin (STZ) at 60 mg / kg (3 mL / kg injection volume), while the normal control group rats received the same volume of citrate buffer. Seventy-two hours after modeling, random blood glucose levels were measured for two consecutive days using a handheld glucometer. A blood glucose level greater than or equal to 16.7 mmol / L was used as the qualifying criterion for paw skin lesioning.

[0097] The selected qualified rats and normal control rats were anesthetized with an area of ​​0.8 cm². 2 Make circular stamps on the insteps of both feet, cut off the outer layer of skin and fascia inside the circular stamps, apply pressure with cotton balls to stop the bleeding, and disinfect with iodine.

[0098] Experimental Groups:

[0099] On the day of skin injury, the rats were weighed. Except for the normal control group, the other rats were randomly divided into eight groups according to their blood glucose levels and body weight 72 hours after STZ modeling. The groups were: normal control group, model control group, two dose groups of Example 1, two dose groups of Example 2, and two dose groups of Example 3, with 10 rats in each group.

[0100] Administration:

[0101] All treatment groups were administered the ointment topically once daily for 14 consecutive days. The normal and model control groups were given a blank ointment, with a dosage of 0.1g ointment / foot, administered topically once daily for 14 consecutive days.

[0102] Detection indicators and results:

[0103] (1) General observation: Observe the mental state and physical signs of the rats daily and record any abnormalities.

[0104] The results showed that, compared with the control group, the model group exhibited increased appetite, increased urination, increased thirst, and disorganized hair. There were no significant differences among the drug-treated groups compared with the model group, demonstrating successful model establishment.

[0105] (2) Healing area and wound healing rate: Anesthetized rats were photographed in a vertical fixed position. The foot injury was recorded before drug administration and on days 3, 7, and 14 after drug administration. The area of ​​injury on the dorsum of the foot was counted. The healing speed was evaluated by comparing with the model group, and the healing area and wound healing rate were calculated. Healing area = original wound area - unhealed wound area, wound healing rate (%) = healed area / original wound area × 100%.

[0106] Before medication, the wound area was 0.8 cm². 2The above-mentioned deep wound infection with abscess, classified as Wagner grade 2+ diabetic foot ulcer, showed that compared with the control group, the healing area and healing rate were significantly reduced in the model group from 3 to 14 days of treatment (P≤0.05, P≤0.01). Compared with the model group, the 0.06 and 0.17 g crude drug / foot group in Example 3 significantly increased the healing area and healing rate at 7 and 14 days of treatment (P≤0.05, P≤0.01).

[0107] The above results indicate that the samples from the embodiments of the present invention have a significant therapeutic effect on Wagner grade 2+ diabetic foot ulcers. Specific results are shown in Table 2.

[0108] Table 2: Effects of Traditional Chinese Medicine Compositions on the Foot Ulcer Area of ​​Diabetic Rats

[0109] Note: Compared with the control group: △△ P≤0.01; Compared with the model group: ** P≤0.01.

[0110] (3) Inflammatory factors: On the 15th day of administration (no administration on the same day), the right foot of the rat was cut off after anesthesia and a 10% homogenate was prepared. The supernatant was collected by centrifugation at 3000 rpm for 10 min at 4℃ and stored at -70℃. The contents of interleukin-1β, tumor necrosis factor-α, vascular endothelial growth factor, transforming growth factor-β (IL-1β, TNF-α, VEGF, TGF-β) and total protein in the tissue homogenate were detected according to the method shown in the kit instructions.

[0111] The results showed that, compared with the control group, the levels of IL-1β, TNF-α, and TGF-β in the foot wound tissue homogenate of the model group were significantly increased, while the VEGF level was significantly decreased (P≤0.01). Compared with the model group, after 14 days of administration, the 0.06 and 0.17 g crude drug / foot groups in Example 1 and Example 2 significantly reduced the levels of IL-1β and TNF-α (P≤0.05); the 0.06 and 0.17 g crude drug / foot groups in Example 3 significantly reduced the levels of IL-1β, TNF-α, and TGF-β, and increased the VEGF level (P≤0.05, P≤0.01).

[0112] The above results indicate that Example 3 has a significant anti-inflammatory effect, significantly reducing the levels of IL-1β, TNF-α, and TGF-β, while increasing the level of VEGF. Transforming growth factor-β (TGF-β) has the effects of inhibiting inflammation, inhibiting epithelial cell formation, and inhibiting vascular endothelial cell growth. Vascular endothelial growth factor (VEGF) can promote the formation of new capillaries and improve tissue blood supply. Specific results are shown in Table 3.

[0113] Table 3: Effects of Traditional Chinese Medicine Composition on Inflammatory Factors in Streptozotocin-Induced Diabetic Rats

[0114]

[0115] Note: Compared with the control group: △△ P≤0.01; Compared with the model group: P≤0.05, ** P≤0.01.

[0116] (4) Histopathology: On day 15 of drug administration (no drug administration on the same day), the injured tissue of the right dorsum of the rat was taken after anesthesia, fixed in 10% neutral formalin, and then dehydrated, embedded, sectioned, stained and mounted. HE staining (to observe inflammatory cell infiltration, angiogenesis, re-epithelialization, skin appendages, etc.) and Masson staining (to observe collagen fiber formation) were used for qualitative judgment and semi-quantitative analysis.

[0117] Diagnostic criteria:

[0118] - No lesions;

[0119] ±: Mild lesions, with visible epidermal thickening and regeneration, a small amount of inflammatory cell infiltration in the dermis, disappearance of hair follicles and skin appendages, and proliferation of fibrous tissue;

[0120] +: Mild lesions, with thickened and regenerated epidermis, less necrosis and crusting, dermal cell infiltration, disappearance of hair follicles and skin appendages, and proliferation of fibrous tissue;

[0121] ++: Moderate lesions, with epidermal necrosis, crusting, dermal necrosis (or accompanied by edema), inflammatory cell infiltration, disappearance of hair follicles and skin appendages, neovascularization, and formation of a small amount of fibrous tissue;

[0122] +++: Severe lesions, with extensive epidermal necrosis and crusting, extensive dermal necrosis (or accompanied by edema), inflammatory cell infiltration, disappearance of hair follicles and skin appendages, neovascularization, and the formation of a small amount of fibrous tissue.

[0123] (5) Immunofluorescence: After dewaxing to water and antigen retrieval, paraffin sections were incubated overnight at 5°C with appropriate concentrations of primary antibodies (CD31, α-SMA) at water and antigen retrieval. The sections were then stained with the corresponding fluorescent secondary antibodies for further incubation. Finally, DAPI staining was used to facilitate nucleus localization, and the sections were mounted. Observation and analysis were performed using a confocal microscope, and the positive intensity of the corresponding indicators was measured. Results showed that under the microscope, epidermal necrosis and crusting, dermal necrosis (or accompanied by edema), inflammatory cell infiltration, disappearance of hair follicles and skin appendages, and neovascularization and a small amount of fibrous tissue formation were observed in the control group.

[0124] Compared with the control group, the model group also showed epidermal necrosis and crusting, dermal necrosis (or accompanied by edema), inflammatory cell infiltration, disappearance of hair follicles and skin appendages, neovascularization and a small amount of fibrous tissue formation, indicating a more severe lesion, which proved that the modeling was successful.

[0125] Compared with the model group, all other treatment groups showed epidermal necrosis and crusting, dermal necrosis (or accompanied by edema), inflammatory cell infiltration, disappearance of hair follicles and skin appendages, and neovascularization and a small amount of fibrous tissue formation. In Example 3, the 0.06g and 0.17g crude drug / foot groups showed reduced lesion severity and better efficacy. The incidence and severity of lesions in each treatment group are detailed in Table 4. Figure 1 .

[0126] The above results indicate that, compared with the model group, the 0.06g and 0.17g raw herbs / foot groups in Example 3 can significantly reduce the severity of the lesions and have good therapeutic effects.

[0127] Table 4: Effects of traditional Chinese medicine composition on the histopathology of streptozotocin-induced diabetic rats

[0128] (Mean±SEM, n=10)

[0129]

[0130] Note: -: no lesion; ±: slight lesion; +: mild lesion; ++: moderate lesion; +++: severe lesion. (5) Immunofluorescence

[0131] Paraffin sections were dewaxed to water and subjected to antigen retrieval. Appropriate concentrations of primary antibodies (CD31, α-SMA) were added, and the sections were incubated overnight at 5°C. The corresponding fluorescent secondary antibodies were then added for further incubation. Finally, DAPI staining was used to facilitate nucleus localization, and the sections were mounted. Observation and analysis were performed using a confocal microscope, and the positive intensity of the corresponding indicators was measured.

[0132] The results showed that, compared with the control group, the expression of CD31 and α-SMA at the foot wound site was significantly reduced in the model group (P≤0.01). Compared with the model group, after 14 days of administration, the 0.06 and 0.17 g crude drug / foot groups in Example 3 significantly increased the expression of CD31 and α-SMA at the foot wound site (P≤0.05, P≤0.01).

[0133] CD31 is involved in leukocyte migration and angiogenesis activation. α-SMA (α-smooth muscle actin) is a protein mainly expressed in smooth muscle cells and myofibroblasts, responsible for maintaining cell morphology, contractile function, and tissue repair.

[0134] The above results indicate that the samples of this invention, through the expression of CD31 and α-SMA at the foot wound site, exert angiogenesis and tissue repair effects, thereby promoting wound healing. Specific results are shown in Table 5.

[0135] Table 5: Effects of traditional Chinese medicine composition on immunofluorescence expression in streptozotocin-induced diabetic rats

[0136] (Mean±SEM, n=10)

[0137]

[0138] Note: Compared with the control group: △△P≤0.01; Compared with the model group: * P≤0.05, ** P≤0.01.

[0139] In the above embodiments, Xiangleitang Foot Cream was used as a positive control drug for comparison. The composition of the present invention is significantly superior to Xiangleitang Foot Cream in the two core dimensions of anti-inflammatory strength and repair quality.

[0140] Example 7 shows that:

[0141] The composition of this invention can promote wound healing in Wagner grade 2+ diabetic foot, filling a treatment gap in this field.

[0142] The composition of the present invention has significant anti-inflammatory effects and can significantly reduce the levels of interleukin-1 (IL-1β) and α tumor necrosis factor (TNF-α).

[0143] The composition of the present invention can promote angiogenesis and tissue repair by reducing transforming growth factor-β (TGF-β) and increasing vascular endothelial growth factor (VEGF) at foot wound sites, and by increasing the expression of CD31 and α-SMA at foot wound sites, thereby promoting wound healing.

[0144] Example 8: Formulation Study of the Compositions of the Invention

[0145] Experimental drug preparation methods

[0146] The complete formula: namely, Example 3.

[0147] Formula 1: This refers to the tonifying herbs in the complete formula, including 200 parts of raw Astragalus membranaceus and 100 parts of Cornus officinalis. The preparation method is the same as in Example 3, except that the number of herbs is reduced.

[0148] Formula 2: This consists of the drying and moistening herbs in the whole formula, including 200 parts of Coptis chinensis, 200 parts of Scutellaria baicalensis, 100 parts of Atractylodes lancea, and 100 parts of Phellodendron chinense. The preparation method is the same as in Example 3, except that the number of herbs is reduced.

[0149] Formula 3: This refers to the blood-activating herbs in the complete formula, including 150 parts Angelica sinensis, 50 parts Lithospermum erythrorhizon, and 5 parts artificial musk. The preparation method is the same as in Example 3, except that the number of herbs is reduced.

[0150] Formula 4: This consists of the tissue-regenerating herbs in the whole formula, including 50 parts of Bai Lian (Radix Ampelopsis) and 50 parts of pearl powder. The preparation method is the same as in Example 3, except that the number of herbs is reduced.

[0151] (1) Effects of the whole formula and its components on the survival rate of vascular endothelial cells:

[0152] Experimental objective: To compare the protective effects of the whole formula and its individual components on vascular endothelial cells using cell viability indicators.

[0153] Experimental methods:

[0154] Cell resuscitation: Human umbilical vein endothelial cells (immortified) HUVEC-SV40T were used. Cell cryopreservation tubes were removed from the liquid nitrogen container and rapidly thawed in a 37°C water bath until the cryopreservation solution was completely thawed. After sterilizing the outer wall of the cryopreservation tubes with 75% ethanol, the cell suspension was transferred to a 15ml centrifuge tube containing 5ml of complete culture medium and centrifuged at 1000rpm for 5min. The supernatant was discarded, and the cell pellet was resuspended in 5ml of complete culture medium. The cells were then seeded into T25 culture flasks and cultured in a 37°C, 5% CO2 cell culture incubator.

[0155] Cell passage: Passage the cells when they reach approximately 80% confluence. Discard the culture medium, wash the cells once with PBS, add 1 ml of 0.25% trypsin digestion solution, and observe under an inverted microscope. Once the cells have shrunk and become rounded, add 5 ml of complete culture medium to stop the digestion. Gently pipette to detach the cells from the culture vessel, transfer the cell suspension to a 15 ml centrifuge tube, and centrifuge at 1000 rpm for 5 min. Discard the supernatant, resuspend the cells in 1–2 ml of complete culture medium, and passage them in two T25 culture flasks at a 1:2 ratio. Add complete culture medium to 5–8 ml per flask and continue culturing in a 37°C, 5% CO2 cell culture incubator.

[0156] Cell digestion, counting, and plating: Logarithmically growing cells were digested with trypsin and counted. 3000 cells per well were seeded into a culture plate in a volume of 100 μl. After routine culture until the cells adhered, appropriate drug intervention was administered.

[0157] Cellular high glucose model: After cells were seeded in culture plates and cultured until they adhered stably, the medium was replaced with complete medium containing 100 mM glucose. Normal glucose concentration (5.5 mM) was used as the control group. The cells were placed in a 37℃, 5% CO2 incubator for 24 h for intervention.

[0158] Drug intervention: The normal control group (Group A) was cultured in normal glucose medium; the model group (Group B) was incubated in 100mM glucose medium for 24 h; the remaining groups (Group CH) were first treated with 100mM glucose for 24 h to establish a high glucose model, and then the medium was replaced with extracts (0.01g / L) of the whole formula, tonifying herbs, drying herbs, blood-activating herbs, and tissue-regenerating herbs, and incubated for another 24 h. Subsequent tests were conducted after the intervention.

[0159] CCK8 assay: Add 10 μl of CCK-8 solution to each well; incubate for 1 hour in a cell culture incubator; measure absorbance at 450 nm using a microplate reader.

[0160] Cell viability calculation: Viability (%) = (Experimental OD value - Blank control OD value) / (Negative control OD value - Blank control OD value) * 100%

[0161] Experimental OD value: absorbance of wells containing cells, CCK-8 solution, and drug solution.

[0162] Blank control OD value: absorbance of pores containing culture medium and CCK-8 solution but without cells.

[0163] Negative control OD value: absorbance of the well containing cells and CCK-8 solution but not the drug solution.

[0164] The experimental results are shown in Table 6.

[0165] Table 6: Effects of whole and individual herbal compositions on cell viability

[0166]

[0167] In summary, the full-formula group had the highest cell survival rate, which was superior to other fractionated groups.

[0168] (2) Effects of the whole formula and its components on VEGF in vascular endothelial cells

[0169] Experimental objective: To investigate the effects of different drug interventions on the VEGF secretion of hyperglycemic hyperplasia-induced vascular endothelial cells (HUVECs), compare the intervention effects of the whole formula and the extracts of each component formula (tonifying, drying, promoting blood circulation, and promoting tissue regeneration), and clarify the differences in their effects.

[0170] Experimental methods:

[0171] Cell passage: Same as "(1) Effect of whole formula and split formula on vascular endothelial cell survival rate".

[0172] Cellular hyperglycemia model: Same as "(1) Effect of whole formula and component formula on vascular endothelial cell survival rate".

[0173] Drug intervention: Same as "(1) Effect of whole formula and split formula on vascular endothelial cell survival rate".

[0174] VEGF assay: The cell culture supernatant was centrifuged at 1000×g for 20 minutes, and the supernatant was collected for subsequent detection.

[0175] ① Remove the required strips from the aluminum foil bag after equilibration at room temperature for 20 minutes, and seal the remaining strips in a self-sealing bag and return them to 4℃.

[0176] ② Set up standard wells (standard concentrations are 2000, 1000, 500, 250, 125, and 62.5 pg / ml respectively) and sample wells. Add 50 μL of standard at different concentrations to each standard well.

[0177] ③ Add 50 μL of the sample to be tested to the sample well; do not add any to the blank well.

[0178] ④ Except for the blank wells, add 100 μL of horseradish peroxidase (HRP)-labeled detection antibody to each of the standard and sample wells, seal the reaction wells with sealing film, and incubate at 37°C in a water bath or incubator for 60 min.

[0179] ⑤ Discard the liquid, pat dry on absorbent paper, fill each well with washing solution (350μL), let stand for 1 minute, shake off the washing solution, pat dry on absorbent paper, and repeat this washing process 5 times.

[0180] ⑥ Add 50 μL of substrate A and 50 μL of substrate B to each well and incubate at 37°C in the dark for 15 min.

[0181] ⑦ Add 50 μL of stop solution to each well, and measure the OD value of each well at a wavelength of 450 nm within 15 min.

[0182] The experimental results are shown in Table 7.

[0183] Table 7: Comparison of the effects of different formulations on VEGF

[0184]

[0185] Note: Compared with the normal group: △ P≤0.05, △△ P≤0.01; Compared with the model group: * P≤0.05, ** P≤0.01; Compared with the full-strength group: # P≤0.05, ## P≤0.01.

[0186] In summary, the whole formula has the strongest effect in promoting the secretion of VEGF by vascular endothelial cells, which is superior to the individual formulas.

[0187] (3) Effects of the whole formula and its components on angiogenesis

[0188] Experimental objective: To observe the effects of the whole formula and its individual components on angiogenesis, and to compare the differences between the whole formula and its individual components.

[0189] Experimental methods

[0190] Cell passage: Same as "(1) Effect of whole formula and split formula on vascular endothelial cell survival rate".

[0191] Cellular hyperglycemia model: Same as "(1) Effect of whole formula and component formula on vascular endothelial cell survival rate".

[0192] Drug intervention: Same as "(1) Effect of whole formula and split formula on vascular endothelial cell survival rate".

[0193] Angiogenesis detection:

[0194] ① Preparation of the substrate gel: Place the substrate gel in a 4°C freezer overnight 24 hours in advance to thaw and set aside; the next day, place the 24-well plate on an ice box, dilute the substrate gel 1:1 by half, and centrifuge to mix the substrate gel with the culture medium. Add 100 μL of substrate gel to each well of the 24-well plate; when adding the substrate gel, be sure to drop it vertically into the bottom of the well to reduce the formation of air bubbles, and use a shaking method to distribute the gel evenly; place it in an incubator for 30-60 minutes to allow it to form a gel;

[0195] ② Angiogenesis: After the HUVEC cells reach 80% confluence, they are prepared for digestion. The cells are collected for counting, and the cell concentration is adjusted by gradient dilution according to requirements. 200 μL of HUVEC cell suspension is added to a 24-well plate, with a concentration of approximately 200,000 cells. The plate is then incubated at 37°C in a 5% CO2 cell culture incubator.

[0196] ③ Take photos of the blood vessel growth.

[0197] Experimental results are as follows Figure 2 As shown:

[0198] Compared with the normal group, the microvessels in the model group had irregular morphology, disordered and poor integrity of lumen structure, rough endothelial connections, and twisted and coarse vascular branches; the number of microvessels was also slightly reduced.

[0199] Compared with the model group, after comprehensive intervention, the morphology and structure of microvessels were significantly improved, the lumen was smooth and regular, the endothelial continuity was better, and the quality of angiogenesis was significantly improved; at the same time, the number of microvessels increased, but the morphology and number of vessels were still slightly inferior to those in the normal group.

[0200] Compared with the model group, the number of microvessels in each of the individual formula groups increased only slightly and the vascular structure improved only slightly, but the degree of improvement was significantly weaker than that in the full formula group.

[0201] In summary, the whole formula has the strongest effect in promoting new blood vessel formation, which is superior to the individual formulas.

[0202] (4) Given that in the Wagner classification of diabetic foot, grade 1 (superficial ulcer) ulcers only involve the epidermis or dermis, while grade 2 (deep ulcer) ulcers extend to the tendons and are mainly muscle ulcers and necrosis, and the composition of the present invention is used to treat grade 2 and above diabetic foot ulcers, further research was conducted using skeletal muscle myoblasts to observe the protective effect of the composition of the present invention on skeletal muscle myoblasts and the promoting effect on VEGF production in skeletal muscle myoblasts.

[0203] The experiment used mouse skeletal muscle myoblasts C2C12, which were routinely cultured in DMEM medium containing 10% FBS. After the cells reached 80% confluence, the medium was replaced with differentiation medium containing 2% horse serum to induce differentiation for 3–5 days. Cells were divided into three groups: Group A (normal control), Group B (model group), and Group C (drug intervention group). Group A: Normal control, no treatment. Group B: Cobalt chloride (CoCl) was added. CoCl inactivates prolyl hydroxylase (PHD), initiating transcription of the downstream hypoxia response element (HRE), simulating hypoxic necrosis of muscle in human diabetic foot. Group C: Drug intervention group, in addition to the established model, received intervention with the composition of this invention for 12 hours. Detection indicators included:

[0204] Cell survival rate: The survival rate of skeletal muscle myoblasts in each group was observed using the CCK8 assay.

[0205] VEGF content detection: The VEGF content in the cell supernatant was detected by ELISA.

[0206] Detecting VEGF changes at the gene level: Total RNA was extracted, cDNA was synthesized by reverse transcription, mouse VEGF-specific primers were designed, qPCR was performed, ΔΔCt values ​​were calculated, and the relative expression level of VEGF mRNA was analyzed.

[0207] VEGF expression was observed using confocal microscopy: Cells were fixed (4% paraformaldehyde). Permeabilization (0.1% Triton X-100) + blocking (5% BSA); incubation with primary antibody, anti-VEGF antibody (rabbit anti-mouse VEGF); incubation with fluorescent secondary antibody (Alexa Fluor 488 labeled goat anti-rabbit IgG); nuclear staining (DAPI); confocal microscopy revealed a significant increase in cytoplasmic fluorescence intensity when VEGF expression was enhanced.

[0208] The results showed that this composition can improve the survival rate of skeletal muscle myoblasts, protect cells, and combat hypoxic damage. It can also promote the secretion of VEGF by skeletal muscle myoblasts at the protein, gene, and microstructure levels, thereby promoting angiogenesis in muscles, restoring tissue oxygenation, and promoting the healing of grade 2 (deep ulcers) muscle ulcers. This is an important mechanism and advantage of this composition in treating grade 2 and above diabetic foot ulcers, filling the current gap in the availability of drugs for treating grade 2 and above diabetic foot ulcers.

[0209] in conclusion:

[0210] Experimental results showed that the complete formula effectively protected vascular endothelial cells and improved cell survival rate, superior to individual components; it also increased vascular endothelial growth factor (VEGF) levels, superior to individual components; and it exhibited the strongest effect in promoting angiogenesis, superior to individual components. In summary, this composition demonstrates that it can protect vascular endothelial cells, reduce cell damage caused by high glucose, increase VEGF levels, and promote angiogenesis. The complete formula is superior to individual components.

[0211] Meanwhile, VEGF can promote the healing of grade 2 (deep ulcer) and above diabetic foot ulcers, and is a new target of action after anti-inflammatory factors. This experiment shows that the target of action of this composition in the treatment of diabetic foot is VEGF, which fills the gap of new target in the treatment of grade 2 (deep ulcer) and above diabetic foot ulcers by traditional Chinese medicine.

[0212] Example 9: Acute toxicity test of the traditional Chinese medicine composition of the present invention

[0213] Experimental animals: SD rats, SPF grade, 36 rats, half male and half female. The experiment was divided into 4 groups: blank control group, Example 1 group, Example 2 group and Example 3 group, with 4 animals in each group.

[0214] Dosage setting:

[0215] Blank control group: The treatment area was 10% of the body surface area (approximately 31 cm² for a 200g rat). 2 The dosage was 0.28 g / cm2, the local dose was 0 g crude drug / cm2, and the systemic dose was 0 g crude drug / kg.

[0216] Example 1 group: The drug administration area was 10% of the body surface area (approximately 31 cm² for a 200g rat). 2 The dosage is 0.223 g / cm², with a local dose of approximately 0.48 g crude drug / cm², which is 0.38 times the clinical local dose. The systemic dose is approximately 74.4 g crude drug / kg, which is 3.15 times the clinical systemic dose.

[0217] Example 2 group: The drug application area was 10% of the body surface area (approximately 31 cm2 for a 200g rat), the drug dosage was 0.204g / cm2, the local dose was approximately 0.48g crude drug / cm2, which is 0.38 times the clinical local dose. The systemic dose was approximately 74.4g crude drug / kg, which is 3.15 times the clinical systemic dose.

[0218] Example 3: The drug application area was 10% of the body surface area (approximately 31 cm² for a 200g rat), and the dosage was 0.28g / cm². The local dose was approximately 0.48g crude drug / cm², which is 0.38 times the clinical local dose. The systemic dose was approximately 74.4g crude drug / kg, which is 3.15 times the clinical systemic dose.

[0219] Experimental procedure:

[0220] The above samples were applied to broken skin, and each group was given the medication once every 24 hours for 24 hours.

[0221] Inspection indicators:

[0222] After applying the medication on the day of administration, observe the rats continuously for about 4 hours, from Day 2 to Day 15, once a day; check the weight once on Day 1, Day 2, Day 4, Day 8, and Day 15; perform gross necropsy on the surviving rats on Day 16.

[0223] Experimental results:

[0224] Clinical observation: During the experiment, no obvious abnormal signs were observed in any group of animals, and no animals died in any group.

[0225] Weight checks: During the experiment, no significant abnormalities related to the test substance were observed in the average weight of animals in each drug administration group at each examination time point.

[0226] Gross anatomical examination: Day 16, no obvious pathological changes were observed in any group of animals.

[0227] Acute toxicology studies showed that the maximum tolerated dose (MTD) for Example 1 was >74.4 g crude drug / kg, the maximum tolerated dose (MTD) for Example 2 was >74.4 g crude drug / kg, and the maximum tolerated dose (MTD) for Example 3 was >74.4 g crude drug / kg. Clinical observation and weight checks of the extracts from Examples 1 to 3 did not induce any toxic reactions in rats, indicating that the compositions of this invention have good safety.

[0228] Example 10 Clinical Effect

[0229] The herbal composition described in this application has been used clinically to treat patients with diabetic foot Wagner grade 2 and above. More than 10 patients with diabetic foot Wagner grade 2 and above have been treated at the Da'ao Traditional Chinese Medicine Clinic. Clinical trials have shown that the herbal composition of this invention has good healing effects on ulcers that penetrate subcutaneous fat to the fascia and muscle, as well as on soft or hard scabs with poor blood supply. Long-term use of this formula is safe, and no damage to the blood system or liver and kidney function has been observed.

[0230] Typical specific cases:

[0231] Case 1: Diabetic foot with damp-heat toxicity and blood stasis (Wagner grade 2+)

[0232] Basic information:

[0233] Patient: Male, 62 years old

[0234] Chief complaint: 30-year history of diabetes, over 30-year history of smoking, and over 20-year history of alcohol consumption. An infection in the right ring toe spread to the deep metacarpophalangeal space, resulting in the surgical amputation of three toes. A subsequent infection at the metacarpal bone of the right little toe led to acute cellulitis of the right foot and lower extremities. Antibiotics were administered intravenously, and open debridement was performed on the infected area of ​​the right foot, removing necrotic tissue and exposing part of the metacarpal bone. The wound gradually enlarged, accompanied by redness, swelling, and pain, which worsened with walking, with no significant granulation tissue growth.

[0235] Past medical history: Type 2 diabetes for about 30 years, oral metformin and glimepiride, with poor glycemic control (fasting blood glucose 8.5–10.2 mmol / L, 2-hour postprandial blood glucose 12.0–14.5 mmol / L).

[0236] Present Illness: Vital signs: T 36.8℃. Specialist Examination: A 2.8cm × 2.2cm ulcer is visible on the lateral side of the right foot joint, with a depth of approximately 0.8cm. The ulcer base is dark red, the edges are black, there is tissue loss, and granulation tissue is exposed at the base with a small amount of yellowish-white purulent discharge. The surrounding skin is red, swollen, dry, and pigmented, with increased skin temperature. No obvious abnormalities were found in the left foot. The condition of the right foot is described below. Figure 3 As shown. Wagner classification: Right foot grade 2+ (deep ulcer).

[0237] Treatment plan: Under aseptic conditions, necrotic tissue and purulent secretions were removed, and the wound was rinsed with physiological saline. The herbal composition of this invention (Example 3) was applied evenly to the wound to a thickness of approximately 0.8 cm, covered with sterile gauze, and secured with adhesive tape. The dressing was changed once daily. See the attached photograph for a detailed description of the application of Example 3 after debridement. Figure 4 As shown.

[0238] Therapeutic effect observation:

[0239] Day 14 of treatment: The redness and swelling of the wound have significantly decreased, secretions have reduced, the base has turned light red, most of the wound secretions have disappeared, the surrounding redness and swelling have subsided, the wound area has shrunk to 1.5cm × 1.0cm, granulation tissue is growing well, and the edges are surrounded by yellowish-white necrotic tissue and scabs. See photos for details. Figure 5 As shown.

[0240] Day 30 of treatment: The wound has basically healed, with only a small amount of residual epithelial growths remaining, and a superficial scab has formed. Patients can walk freely. See photos for details. Figure 6 As shown.

[0241] Day 60 of treatment: The wound has scabbed over, the local skin color is close to normal, and there is no scar contracture. See photos for details. Figure 7 As shown.

[0242] Evaluation of therapeutic effect: Clinical cure: clinical symptoms disappeared and the wound was completely healed.

[0243] Follow-up for 6 months: No recurrence of lesions has been found to date.

[0244] Case 2:

[0245] Patient 2, female, 68 years old, with a history of diabetes for over 20 years, no history of smoking or drinking. The affected area presented as a round, open ulcer with raised edges, a red base with exudation, and surrounding skin that was swollen and red, showing signs of infection and slight desquamation. Diagnosed as diabetic foot Wagner grade 2+. See attached photos. Figure 8 As shown in Part A.

[0246] After debridement, the composition of this invention (same as in Case 1) was applied. On the 7th day of treatment, the ulcer area slightly decreased, granulation tissue began to form at the edges, and the central area turned yellow, indicating necrotic tissue or fibrosis. See specific photos. Figure 8 As shown in Part B.

[0247] On the 14th day of treatment, the lesions further shrank, covered with a pale yellow scab, and the surrounding skin showed increased pigmentation and a flattened shape, with no obvious exudation. See photos below. Figure 8 As shown in section C.

[0248] On day 28 of treatment, the wound was mostly closed, leaving a superficial depressed scar. The surface was dry, with visible new skin texture and uneven pigmentation. See photos for details. Figure 8 As shown in part D.

[0249] On day 42 of treatment, significant scar tissue hyperplasia was observed, with a slightly raised surface, yellowish-brown color, and blurred borders with normal skin. The skin felt firm to the touch. The skin surface was smooth and even, with only minor hypopigmented patches remaining. Skin texture had almost returned to normal, and there was no redness, swelling, or oozing. See photos for details. Figure 8 Parts E and F are shown.

[0250] Case 3:

[0251] Patient 3, male, 76 years old, with a history of diabetes for over 30 years, no smoking history, and a drinking history for over 40 years. Extensive deep purple to dark red necrotic lesions were observed on the sole and toes of his right foot, with significant ulceration and swelling of the skin tissue; exposed muscle and bleeding tissue were visible in some areas, with irregular edges, accompanied by dried scabs and exudate. The skin above the ankle was relatively normal in color, but mild edema was observed in some areas. This is consistent with late-stage severe ischemic gangrene, indicating severe distal blood supply insufficiency; the ulceration with exudate suggests secondary infection or tissue liquefaction. The diagnosis was Diabetic Foot Wagner Grade 3+.

[0252] After debridement, the composition of this invention (same as in Case 1) was applied for three months. The infection was controlled, the wound healed, tissue was repaired, and the surface skin remained relatively intact. See before and after photos. Figure 9 As shown.

[0253] in conclusion:

[0254] Animal experiments and clinical observations show that the combination of Examples 1-3 of the present invention can treat grade 2 (deep ulcer) or higher diabetic foot, filling the treatment gap in this field. Moreover, the therapeutic effect of Example 3 is the best, indicating that the extraction of effective components of traditional Chinese medicine using the process of Example 3 is the most effective.

[0255] Animal and cell experiments have shown that the mechanism of action of this composition is to reduce inflammatory factors such as interleukin-1 (IL-1β) and α-tumor necrosis factor (TNF-α); increase CD31 expression, decrease transforming growth factor-β (TGF-β), and increase vascular endothelial growth factor (VEGF), thereby promoting angiogenesis and improving tissue blood supply; and increase α-SMA expression, promote tissue repair, and accelerate wound healing.

[0256] VEGF can promote the healing of grade 2 (deep ulcer) and above diabetic foot ulcers. It is a new target of action after anti-inflammatory factors. Cell experiments show that the target of this composition for the treatment of diabetic foot is VEGF, which fills the gap of new target for traditional Chinese medicine in the treatment of grade 2 (deep ulcer) and above diabetic foot ulcers.

[0257] The above embodiments are merely illustrative of the principles and effects of the present invention and are not intended to limit the invention. Any person skilled in the art can modify or alter the above embodiments without departing from the spirit and scope of the present invention. Therefore, all equivalent modifications or alterations made by those skilled in the art without departing from the spirit and technical concept disclosed in the present invention should still be covered by the claims of the present invention.

Claims

1. A traditional Chinese medicine composition for external treatment of diabetic foot, characterized in that, The traditional Chinese medicine composition is made from the following raw materials in parts by weight: 180-220 parts of raw Astragalus membranaceus, 140-160 parts of Angelica sinensis, 90-120 parts of Cornus officinalis, 180-220 parts of Coptis chinensis, 180-220 parts of Scutellaria baicalensis, 90-120 parts of Atractylodes lancea, 90-120 parts of Phellodendron chinense, 40-60 parts of Ampelopsis japonica, 40-60 parts of pearl powder, 40-60 parts of Lithospermum erythrorhizon, and 4-8 parts of artificial musk; The preparation method of the traditional Chinese medicine composition includes the following steps: Combine raw Astragalus membranaceus, Angelica sinensis, Cornus officinalis, Coptis chinensis, Scutellaria baicalensis, Atractylodes lancea, Phellodendron chinense, Ampelopsis japonica, and Lithospermum erythrorhizon; add 8-20 times their weight of water, soak for 30-60 minutes, and heat under reflux to extract 1-3 times, each time for 1-3 hours; filter and combine the extracts, then concentrate to a concentrated paste with a relative density of 1.10-1.25; take the concentrated paste, dry under reduced pressure at 60℃-80℃, and pulverize to obtain a dry paste; add pearl powder and artificial musk to the dry paste and mix well to obtain the final product.

2. The traditional Chinese medicine composition according to claim 1, characterized in that, The traditional Chinese medicine composition is made from the following raw materials in parts by weight: 200 parts of raw Astragalus membranaceus, 150 parts of Angelica sinensis, 100 parts of Cornus officinalis, 200 parts of Coptis chinensis, 200 parts of Scutellaria baicalensis, 100 parts of Atractylodes lancea, 100 parts of Phellodendron chinense, 50 parts of Ampelopsis japonica, 50 parts of pearl powder, 50 parts of Lithospermum erythrorhizon, and 5 parts of artificial musk.

3. The traditional Chinese medicine composition according to claim 1 or 2, characterized in that, The dosage form of the traditional Chinese medicine composition is an ointment.

4. The method for preparing the traditional Chinese medicine composition according to claim 1 or 2, characterized in that, The preparation method includes the following steps: Combine raw Astragalus membranaceus, Angelica sinensis, Cornus officinalis, Coptis chinensis, Scutellaria baicalensis, Atractylodes lancea, Phellodendron chinense, Ampelopsis japonica, and Lithospermum erythrorhizon; add 8-20 times their weight of water, soak for 30-60 minutes, and heat under reflux to extract 1-3 times, each time for 1-3 hours; filter and combine the extracts, then concentrate to a concentrated paste with a relative density of 1.10-1.25; take the concentrated paste, dry under reduced pressure at 60℃-80℃, and pulverize to obtain a dry paste; add pearl powder and artificial musk to the dry paste and mix well to obtain the final product.

5. The preparation method according to claim 4, wherein the preparation method comprises the following steps: Combine raw Astragalus membranaceus, Angelica sinensis, Cornus officinalis, Coptis chinensis, Scutellaria baicalensis, Atractylodes lancea, Phellodendron chinense, Ampelopsis japonica, and Lithospermum erythrorhizon; add 8 times their weight of water, soak for 30 minutes, and extract by reflux twice, each time for 1 hour; filter and combine the extracts, then concentrate to a concentrated paste with a relative density of 1.

10. Take the concentrated paste, dry it under reduced pressure at 70°C, and then pulverize it to obtain a dry paste; add pearl powder and artificial musk to the dry paste, mix well, and you have the final product.

6. The use of the traditional Chinese medicine composition according to claim 1 or 2 in the preparation of a medicament for treating diabetic foot.

7. The application according to claim 6, wherein the diabetic foot is Wagner grade 2 or higher diabetic foot.

8. The application according to claim 6, wherein the drug promotes ulcer healing and promotes angiogenesis.

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