Traditional Chinese medicine composition, preparation method and application of traditional Chinese medicine composition in preparation of medicine for preventing or treating diabetic foot

Abstract

The invention relates to the field of traditional Chinese medicine, in particular to a traditional Chinese medicine composition, a preparation method and application of the traditional Chinese medicine composition to preparation of medicine for preventing or treating diabetic foot. The invention provides a traditional Chinese medicine composition. The traditional Chinese medicine composition is prepared from leech, caulis spatholobi, lumbricus, radix paeoniae rubra, garden balsam stem, radix cyathulae, cassia twig, frankincense, myrrh, radix aconiti lateralis praeparata, angelica sinensis, rheum officinale, coptis chinensis and astragalus membranaceus. All the medicines are combined to play roles in promoting blood circulation and enriching blood, dredging channels and collaterals, improving nerve and blood vessel functions of lower limbs and promoting growth of local granulation tissues, so that the traditional Chinese medicine composition can be used for preventing or treating diabetic foot or complications thereof, and the complications comprise diabetic peripheral vasculopathy or diabetic peripheral neuropathy.

Description

Technical Field

[0001] The present invention relates to the field of traditional Chinese medicine, and in particular to a traditional Chinese medicine composition and a preparation method thereof, and use of the composition in preparing a medicine for preventing or treating diabetic foot. Background Art

[0002] Diabetic foot (DF) is mainly characterized by the destruction of the skin and deep tissues beyond the ankle joint of diabetic patients, complicated by infection and varying degrees of occlusion of lower limb arteries. In severe cases, it often leads to necrosis of muscle and bone tissue.

[0003] Diabetic foot ulcers are a major complication leading to disability and death in diabetic patients, affecting approximately 15% of the diabetic population. 85% of these patients ultimately require amputation, and the five-year survival rate for patients after amputation is less than 50%. Treatment of diabetic foot ulcers is difficult and costly, placing a heavy burden on patients, their families, and society. Effective treatment of ischemic diabetic foot ulcers is a major requirement of my country's health care sector and an urgent social need.

[0004] There are numerous DF classification methods. Currently, the main clinical classifications of diabetic foot are ischemic, neurogenic, and mixed. The pathogenesis of diabetic foot: Long-term hyperglycemia can damage vascular endothelial cells, induce atherosclerosis, and subsequently lead to arterial occlusion. Ischemic diabetic foot is caused by atherosclerosis in the lower limb arteries, which leads to gradual thickening of the vascular lining, resulting in arterial stenosis or even occlusion. In short, diabetic foot characterized by Qi and blood deficiency and blood stasis (ischemic type) is a common type of diabetic foot. It is difficult to treat and has a poor prognosis. Improving blood circulation in the lower limbs and suppressing local inflammation are the main treatment methods. Summary of the Invention

[0005] Therefore, the technical problem to be solved by the present invention is to provide a traditional Chinese medicine composition and a preparation method thereof and use thereof in preparing a medicine for preventing or treating diabetic foot.

[0006] To this end, the present invention provides the following technical solutions:

[0007] In an embodiment of the present invention, a traditional Chinese medicine composition is provided, which is made up of the following raw materials: leech, Millettia reticulata, earthworm, red peony root, radix polygoni lobatae, rhizoma schizonepetae, radix cyperi, cassia twig, frankincense, myrrh, aconite root, angelica sinensis, rhubarb, coptis chinensis, and astragalus. The above-mentioned traditional Chinese medicine composition is an improved prescription of Huiyang Shengji prescription, which adds four herbs to the Huiyang Shengji prescription: leech, Millettia reticulatae, earthworm, and red peony root. The present invention has found that the improved prescription of the present invention is more effective in preventing, alleviating or treating diabetic foot or its complications, including diabetic peripheral vascular disease or diabetic peripheral neuropathy, and inflammation caused by diabetic foot, than the Huiyang Shengji prescription before the improvement.

[0008] The aforementioned raw materials—leech, Millettia reticulata, earthworm, red peony root, Cyathula officinalis, cinnamon twig, frankincense, myrrh, angelica, rhubarb, coptis chinensis, and astragalus—are all listed in the 2020 edition of the Chinese Pharmacopoeia. Herba pelargonidis (Phryma leptostachya subsp. asiatica (Hara) Kitamura) is also known as medicinal herb. Fuzi (aconite root) is generally referred to as aconite root. Fuzi, a traditional Chinese medicine, is a processed product of the rootlets of Aconitum carmichaelii Debx, a plant of the Ranunculaceae family.

[0009] In some embodiments, the method comprises the following parts by weight of the raw material:

[0010] 10-30 parts by weight of leech, 10-30 parts by weight of Millettia reticulata, 10-30 parts by weight of earthworm, 10-30 parts by weight of red peony root, 10-30 parts by weight of scutellaria baicalensis, 10-30 parts by weight of Cyathula capitata, 10-30 parts by weight of cinnamon twig, 10-30 parts by weight of frankincense, 10-30 parts by weight of myrrh, 10-30 parts by weight of aconite root, 10-30 parts by weight of angelica sinensis, 10-30 parts by weight of rhubarb, 10-30 parts by weight of coptis chinensis, and 10-30 parts by weight of astragalus.

[0011] An embodiment of the present invention provides a method for preparing the Chinese medicine composition, comprising:

[0012] Weigh the raw materials according to the formula, mix them and perform extraction.

[0013] In some embodiments, the extraction is water extraction: add 5 to 10 times the weight of water to the mixed raw materials, soak for 3 to 5 hours, heat to 60 to 80°C, maintain for 10 to 15 minutes, extract 1 to 2 times, filter, and combine the filtrate.

[0014] An embodiment of the present invention provides a traditional Chinese medicine preparation, comprising the traditional Chinese medicine composition or the traditional Chinese medicine composition prepared by the preparation method of the traditional Chinese medicine composition as an active ingredient.

[0015] In some embodiments, a pharmaceutically acceptable excipient is also included.

[0016] In some embodiments, the traditional Chinese medicine preparation is in the form of a liquid preparation or a solid preparation.

[0017] In some embodiments, the dosage form of the traditional Chinese medicine preparation includes tablets, capsules, powders, granules or pastes;

[0018] Optionally, the dosage form includes pills, injections, granules, powders, oral solutions, sprays, powder injections, sugar-coated tablets, film-coated tablets, enteric-coated tablets, orally disintegrating tablets, hard capsules, soft capsules, lozenges, granules, pills, pastes or disintegrants.

[0019] The embodiments of the present invention provide the use of the Chinese medicine composition or the Chinese medicine composition prepared by the method for preparing the Chinese medicine composition or the Chinese medicine preparation in any of the following aspects:

[0020] (1) Use in the preparation of drugs for preventing, alleviating or treating diabetic foot or its complications;

[0021] (2) Use in the preparation of a drug for preventing, alleviating or treating inflammation caused by diabetic foot;

[0022] (3) Use in the preparation of drugs for preventing, alleviating or treating wound healing of diabetic foot.

[0023] In some embodiments, comprising:

[0024] The complications include diabetic peripheral vascular disease or diabetic peripheral neuropathy;

[0025] and / or, the inflammation caused by diabetic foot includes elevated serum TNF-α and IL-6 levels;

[0026] And / or, the diabetic foot is diabetic foot of qi and blood deficiency type.

[0027] The technical solution of the present invention has the following advantages:

[0028] 1. The present invention provides a Chinese medicine composition, comprising the following raw materials: leech, Spatholobus suberectus, earthworm, red peony root, radix polygoni multiflori, cyathula capitata, cassia twig, frankincense, myrrh, aconite root, angelica, rhubarb, coptis root, and astragalus root; in the above-mentioned Chinese medicine composition, leech, Spatholobus suberectus, earthworm, red peony root, which have the effects of promoting blood circulation, replenishing blood, and dredging meridians and collaterals, are all monarch drugs; astragalus root is good at warming yang and replenishing qi, and expelling toxins; rhubarb has the effect of promoting blood circulation and dredging collaterals, and mobilizing qi and blood throughout the body; coptis root has the effects of clearing away heat and dampness, purging fire and detoxifying, and quenching thirst; They are collectively referred to as ministerial drugs; angelica, frankincense, and myrrh are collectively referred to as adjuvant drugs for dredging the meridians and activating the collaterals, promoting blood circulation and removing blood stasis; radix polygoni lobata is good at promoting blood circulation and removing blood stasis, and is good at dredging the meridians, aconite root is used to assist yang, cinnamon twig warms the meridians and dredges the collaterals, and rhizome of Achyranthes bidentata leads the meridians downward, and also nourishes the liver and kidneys and strengthens the tendons and bones, and are collectively referred to as guiding drugs; the combination of these drugs can activate blood circulation and tonify blood, dredge the meridians and dredge the collaterals, improve the neurovascular function of the lower limbs, and promote the growth of local granulation tissue, and thus can be used to prevent or treat diabetic foot or its complications, including diabetic peripheral vascular disease or diabetic peripheral neuropathy.

[0029] 2. The present invention provides a traditional Chinese medicine composition, which is made from the following raw materials in parts by weight: 10-30 parts by weight of leech, 10-30 parts by weight of Millettia reticulata, 10-30 parts by weight of earthworm, 10-30 parts by weight of red peony root, 10-30 parts by weight of scutellaria baicalensis, 10-30 parts by weight of scutellaria baicalensis, 10-30 parts by weight of Cyathula capitata, 10-30 parts by weight of cinnamon twig, 10-30 parts by weight of frankincense, 10-30 parts by weight of myrrh, 10-30 parts by weight of aconite root, 10-30 parts by weight of angelica sinensis, 10-30 parts by weight of rhubarb, 10-30 parts by weight of coptis chinensis, and 10-30 parts by weight of astragalus. The present invention has found that under the above-selected ratio, the traditional Chinese medicine composition is good at improving the neurovascular function of the lower limbs and promoting the growth of local granulation tissue. DETAILED DESCRIPTION

[0030] The following examples are provided for a better understanding of the present invention and are not intended to limit the best mode of implementation. They do not limit the content and scope of protection of the present invention. Any product identical or similar to the present invention obtained by anyone under the guidance of the present invention or by combining the features of the present invention with other prior arts shall fall within the scope of protection of the present invention.

[0031] If no specific experimental steps or conditions are specified in the examples, the conventional experimental steps or conditions described in the literature in this field can be used. If the manufacturer of the reagents or instruments is not specified, they are all commercially available conventional reagents.

[0032] The Chinese medicinal pieces of leech, Millettia reticulata, earthworm, red peony root, radix polygoni lobatae, cyperus rotundus, cassia twig, frankincense, myrrh, aconite root, angelica, rhubarb, coptis root, and astragalus root involved in the following examples were purchased from the Chinese medicine pharmacy of Longfu Hospital in Beijing.

[0033] Example

[0034] This embodiment provides a Chinese medicine composition, the formula of which is as follows:

[0035] Table 1. Formulation

[0036]

[0037]

[0038] Preparation method of the Chinese medicine composition of Example 1

[0039] This embodiment provides a method for preparing a Chinese medicine composition, comprising the following steps:

[0040] (1) Weigh each Chinese herbal medicine according to the formula, mix well, add 1400 mL of water, and soak for 4 hours;

[0041] (2) The mixture obtained in step (1) was heated to 70° C., maintained for 15 min, and filtered through gauze to obtain a filtrate and a medicinal residue, and the filtrate was collected.

[0042] Preparation method of the Chinese medicine composition of Example 2

[0043] This embodiment provides a method for preparing a Chinese medicine composition, comprising the following steps:

[0044] (1) Weigh each Chinese herbal medicine according to the formula, mix well, add 4200 mL of water, and soak for 3 hours;

[0045] (2) The mixture obtained in step (1) was heated to 60° C., maintained for 10 min, and filtered through gauze to obtain a filtrate and a medicinal residue, and the filtrate was collected.

[0046] Preparation method of the Chinese medicine composition of Example 3

[0047] This embodiment provides a method for preparing a Chinese medicine composition, comprising the following steps:

[0048] (1) Weigh each Chinese herbal medicine according to the formula, mix them evenly, add 5 times the weight of the mixed raw materials in water, and soak for 5 hours;

[0049] (2) The mixture obtained in step (1) was heated to 80° C., maintained for 13 min, and filtered through gauze to obtain a filtrate and a medicinal residue, and the filtrate was collected.

[0050] Preparation method of the Chinese medicine composition of Example 4

[0051] This embodiment provides a method for preparing a Chinese medicine composition, comprising the following steps:

[0052] (1) Weigh each Chinese herbal medicine according to the formula, mix them evenly, add 7 times the weight of the mixed raw materials in water, and soak for 3 hours;

[0053] (2) The mixture obtained in step (1) was heated to 78° C., maintained for 10 min, and filtered through gauze to obtain a filtrate and a medicinal residue, and the filtrate was collected.

[0054] Preparation method of the Chinese medicine composition of Example 5

[0055] This embodiment provides a method for preparing a Chinese medicine composition, comprising the following steps:

[0056] (1) Weigh each Chinese herbal medicine according to the formula, mix well, add 9 times the weight of the mixed raw materials in water, and soak for 4 hours;

[0057] (2) heating the mixture obtained in step (1) to 65° C., maintaining the temperature for 15 min, and filtering the mixture through gauze to obtain a first filtrate and a medicinal residue;

[0058] (3) Add 9 times the weight of the mixed raw material medicine in water to the drug residue in step (2) and soak for 5 hours;

[0059] (4) heating the mixture obtained in step (3) to 65° C., maintaining the temperature for 15 min, and filtering the mixture through gauze to obtain a second filtrate and a medicinal residue;

[0060] (5) Combine the first filtrate and the second filtrate.

[0061] Preparation method of the Chinese medicine composition of Example 6

[0062] This embodiment provides a method for preparing a Chinese medicine composition, comprising the following steps:

[0063] (1) Weigh each Chinese herbal medicine according to the formula, mix them evenly, add 6 times the weight of the mixed raw materials in water, and soak for 5 hours;

[0064] (2) The mixture obtained in step (1) was heated to 70° C., maintained for 12 min, and filtered through gauze to obtain a filtrate and a medicinal residue, and the filtrate was collected.

[0065] Comparative Example 1

[0066] This comparative example provides a traditional Chinese medicine composition, which is prepared from the following raw materials: 10g of Radix schizonepetae radix, 10g of Radix Achyranthis Bidentatae, 10g of cassia twig, 10g of frankincense, 10g of myrrh, 10g of aconite root, 10g of angelica sinensis, 10g of rhubarb, 10g of coptis chinensis, and 10g of astragalus.

[0067] The preparation method is as follows:

[0068] (1) Weigh each Chinese herbal medicine according to the formula, mix well, add 1000 mL of water, and soak for 4 hours;

[0069] (2) The mixture obtained in step (1) was heated to 70° C., maintained for 15 min, and filtered through gauze to obtain a filtrate and a medicinal residue, and the filtrate was collected.

[0070] Experimental Example 1

[0071] 1 Clinical Data

[0072] 1.1 General Data: Sixty patients with diabetic foot due to qi and blood deficiency who were hospitalized at Beijing Longfu Hospital between January 2023 and January 2024 were randomly divided into an experimental group and a control group, with 30 patients in each group. No patients dropped out of either group during the trial. There were no statistically significant differences in gender, age, duration of diabetes, and other general data between the two groups (P>0.05), indicating comparability. See Table 2 for details. This study was approved by the Medical Ethics Committee of Beijing Longfu Hospital (LFYY--2022-30).

[0073] Table 2 Comparison of general information of patients in the experimental group and the control group

[0074] General Information Experimental group (n=30) Control group (n=30) <![CDATA[t / z / χ 2 Value]]> P-value Gender (male / female) / case 17 / 13 18 / 12 1.028 0.223 Average age (x±s) / year 65.4±3.6 69.2±3.1 1.253 0.364 <![CDATA[Average body mass index (x±s) / (kg / m 2 )]]> 25.3±3.7 27.4±2.2 3.264 0.479 Average duration of diabetes (x±s) / year 15.4±4.5 16.3±3.4 2.425 0.264 Wagner classification / case 1.364 0.474 Level 2 7 9 Level 3 15 12 Level 4 8 9

[0075] 1.2 Western Medical Diagnostic Criteria: According to the "Chinese Guidelines for the Diagnosis and Treatment of Diabetic Foot," the diagnostic criteria for diabetic foot include: a history of diabetes; intermittent claudication and rest pain; foot ulcers and gangrene; lower extremity paresthesias; trophic changes in the skin; and foot deformities. Diabetic foot is diagnosed if these conditions are met. Wagner's grading system: Grade 2—deep infection penetrating soft tissue but without osteomyelitis or deep abscesses; Grade 3—deep soft tissue ulcers with associated osteomyelitis or deep abscesses; Grade 4—ischemic gangrene with localized foot infection.

[0076] 1.3 Traditional Chinese Medicine Syndrome Differentiation Criteria: The differentiation criteria for Qi Deficiency and Blood Stasis Syndrome are formulated with reference to the TCM Syndrome Differentiation Criteria for Qi and Blood Deficiency and Blood Vessel Stasis Syndrome in Diabetic Foot Disease, as outlined in the "Guidelines for Integrated Traditional Chinese Medicine Diagnosis and Treatment of Diabetic Foot Disease." Primary symptoms include lower extremity soreness, numbness, decreased or absent sensation, intermittent claudication, pain at rest, pain resembling a needle, and prolonged wound healing. Secondary symptoms include fatigue and weakness; aversion to cold and cold extremities; lower extremity weakness; cool extremities; dry skin; and hair loss. Tongue and Pulse: Pale tongue with a white coating and a thready, wiry pulse. If the primary symptom and two secondary symptoms are present, the syndrome can be differentiated based on the tongue and pulse.

[0077] 1.4 Inclusion criteria: Patients who met the Western medical diagnostic criteria for diabetic foot and the Traditional Chinese Medicine criteria for Qi deficiency and blood stasis syndrome; Wagner grade 2-4 diabetic foot; aged 50-75 years; voluntarily participated in this study and signed the informed consent form.

[0078] 1.5 Exclusion criteria: patients with serious medical diseases; pregnant or lactating women; patients who are allergic to or have contraindications to the drugs used in the study.

[0079] 1.6 Dropout criteria: Patients who have allergic reactions or serious adverse events and the doctor judges that the trial should be stopped; patients with poor compliance and failure to take the medication on time or as designed; patients who withdraw on their own.

[0080] 2 Treatment methods

[0081] Both groups received routine dressing changes daily: routine hydrogen peroxide and iodine disinfection, followed by normal saline irrigation of the wound surface. Consult with the endocrinology department for blood sugar control, blood sugar monitoring, and adjustments to blood sugar fluctuations (pre-meal fasting blood sugar <7 mmol / L, 2-hour post-meal fasting blood sugar <11 mmol / L).

[0082] 2.1 Control Group: After routine dressing changes, the wound surface was soaked with the filtrate obtained in Comparative Example 1. One dose per day, 500 ml per dose. Before use, heat to 30-45°C (40°C in this experimental example). Sterile gauze was soaked in the solution and placed on the wound surface to soak for 20 minutes. The gauze was changed as soon as it cooled slightly during the soaking process.

[0083] 2.2 Experimental Group: After routine dressing changes, the wound surface was soaked with the filtrate obtained in Example 1. One dose per day, 500 ml per dose, was heated to 30-45°C (40°C in this experimental example) before use. Sterile gauze was soaked in the solution and placed on the wound surface to soak for 20 minutes. The gauze was changed as soon as it cooled slightly during the soaking process.

[0084] Patients in both groups were treated with soaking once a day after dressing change, and the course of treatment was 4 weeks.

[0085] 3. Observation of therapeutic effects

[0086] 3.1 Observation indicators

[0087] 3.1.1 Peripheral Nerve Function: The Michigan Neurological Screening Scale (MNSI) was used to assess peripheral nerve function in both groups before and after treatment. The maximum score on this scale is 10, and a total score greater than 5 is considered diagnostic of neuropathy. Scoring criteria for each individual item are as follows: normal foot appearance (0 point), abnormal (1 point); absence (0 point), presence (1 point); ankle reflex (0 point), decreased or hyperactive (0.5 point), or absent (1 point); nylon monofilament tactile sensation (0 point), decreased (0.5 point), or absent (1 point); and vibration sensation in the great toe (0 point), decreased (0.5 point), or absent (1 point). The total score is the sum of the individual scores; a higher total score indicates worse peripheral nerve function. Nerve conduction velocity testing: The motor nerve conduction velocity (MNCV) and sensory nerve conduction velocity (sNCV) of the common peroneal nerve, tibial nerve, median nerve, and superficial peroneal nerve were measured using an MEB-9200K electromyographic evoked potential (EME) device.

[0088] 3.1.2 Peripheral Vascular Function: Peripheral vascular recovery in both groups was assessed before and after treatment using the ankle-brachial index (ABI), transcutaneous oxygen partial pressure, and dorsal foot skin temperature (measurements were recommended after 30 minutes of rest). Doppler ultrasound (Terason, model: 3000c) and a sphygmomanometer (Yuyue, model: YE660A) were used to measure the highest ankle systolic pressure and the highest brachial artery systolic pressure at the affected limb, and the ratio was calculated (normal values ​​are 0.9-1.3, 0.71-0.89 indicates mild ischemia, 0.5-0.7 indicates moderate ischemia, and less than 0.5 indicates severe ischemia). A transcutaneous oxygen partial pressure monitor (Radiometer, model: TCM400) was used to measure the oxygen partial pressure at the intact skin of the anterior tibia closest to the wound surface, and an infrared skin thermometer (Beilcon, model: JXB-182) was used to measure the dorsal foot skin temperature. The monitoring point was the midpoint of the medial and lateral ankle joint lines.

[0089] Dorsal artery color Doppler ultrasound hemodynamic parameters were compared between the study group and the study group, including vessel diameter, peak systolic velocity (Vs), early diastolic reverse velocity (Vr), and diastolic forward velocity (Vd). Measurements were made using a Konica Minolta HS-1 ultrasound system with a wideband probe frequency of 11-3L and an acoustic beam angle of <60° to blood flow. The common femoral, superficial femoral, deep femoral, popliteal, anterior tibial, posterior tibial, and dorsalis pedis arteries were observed. Intima-media thickness, arteriosclerosis and plaque thickness were measured, and lumen stenosis rate was calculated. Peak velocity, resistance index, and pulsatility index were also measured in each artery.

[0090] 3.2 Statistical Methods: Data were analyzed using SPSS 27.0 statistical software. All measured data in this study conformed to a normal distribution and were expressed as mean ± standard deviation (x ± s). Within-group comparisons were performed using the paired-sample t-test, and between-group comparisons were performed using the independent-sample t-test. Enumeration data were expressed as cases or percentages and tested using the chi-square test. A P < 0.05 was considered statistically significant.

[0091] 3.3 Treatment outcomes

[0092] 3.3.1 Comparison of peripheral nerve function in 2 groups of patients before and after treatment

[0093] Before treatment, there were no statistically significant differences in the total MNSI score and individual scores between the two groups (P>0.05). After treatment, these scores were significantly lower in both groups compared to their pre-treatment scores (P<0.05), with the experimental group's scores significantly lower than the control group's (P<0.05). See Table 3.

[0094] Table 3 Comparison of MNSI scores before and after treatment in the experimental group and the control group (x±s) Unit: points

[0095]

[0096]

[0097] Note: Compared with the group before treatment, #P<0.05; compared with the control group after treatment, △P<0.05.

[0098] Before treatment, there was no statistically significant difference in tibial nerve conduction velocity and common peroneal nerve conduction velocity between the two groups (P>0.05). After treatment, these results were significantly improved in both groups (P<0.05), with the experimental group showing significantly higher values ​​than the control group (P<0.05). See Table 4.

[0099] Table 4. Comparison of nerve conduction velocity between the two groups of patients (x±s) Unit: m / s

[0100]

[0101] 3.3.2 Comparison of peripheral vascular function and pain in 2 groups of patients before and after treatment

[0102] Before treatment, no statistically significant differences were found in pain VAS scores, ankle-brachial index, transcutaneous oxygen pressure, and dorsal foot skin temperature between the two groups (P>0.05). After treatment, ankle-brachial index, transcutaneous oxygen pressure, and dorsal foot skin temperature were significantly higher in both groups compared with those before treatment (P<0.05), and these indicators were significantly higher in the treatment group than in the control group (P<0.05). After treatment, pain VAS scores were significantly lower in both groups compared with those before treatment (P<0.05), with those in the treatment group significantly lower than those in the control group (P<0.05). See Table 5.

[0103] Table 5 Comparison of peripheral vascular function and pain in the experimental group and the control group before and after treatment (x±s)

[0104]

[0105] Note: Compared with the pre-treatment group, #P<0.05; compared with the control group after treatment, △P<0.05. 1mmHg≈0.133kPa.

[0106] Before treatment, there were no statistically significant differences in vascular diameter, peak systolic velocity (Vs), early diastolic reverse velocity (Vr), and diastolic forward velocity (Vd) between the two groups (P>0.05). After treatment, vascular diameter, peak systolic velocity (Vs), early diastolic reverse velocity (Vr), and diastolic forward velocity (Vd) improved in both groups compared with those before treatment. Vr and Vd improved in the control group compared with those before treatment, with statistically significant differences (P<0.01). There were also statistically significant differences in Vr and Vd between the experimental group and the control group after treatment (P<0.01), indicating that the hemodynamics of the dorsalis pedis artery improved more significantly in the experimental group than in the control group. See Table 6.

[0107] Table 6 Comparison of hemodynamic parameters of dorsalis pedis artery in the two groups (x±s)

[0108]

[0109] Note: Compared with the group before treatment, #P<0.05; compared with the control group after treatment, △P<0.05.

[0110] In summary, compared with the unimproved Chinese medicine composition of the control group, the improved Chinese medicine composition of the present invention has a significant improvement and therapeutic effect on the peripheral nerve dysfunction of diabetic foot caused by qi and blood deficiency. It can be concluded that compared with the unimproved Chinese medicine composition of the control group, the improved Chinese medicine composition of the present invention has a significant improvement and therapeutic effect on the peripheral vascular dysfunction of diabetic foot caused by qi and blood deficiency.

[0111] Experimental Example 2

[0112] 1 Clinical Data

[0113] 1.1 General Data: Sixty patients with diabetic foot due to qi and blood deficiency who were hospitalized at Beijing Longfu Hospital between January 2023 and January 2024 were randomly divided into a study group and a control group, with 30 patients in each group. No patients dropped out of either group during the trial. There were no statistically significant differences in gender, age, duration of diabetes, and other general data between the two groups (P>0.05), indicating comparability. See Table 7 for details. This study was approved by the Medical Ethics Committee of Beijing Longfu Hospital (LFYY-2022-30).

[0114] Table 7 Comparison of general information of patients in the treatment group and the control group

[0115] General Information Study group (n=30) Control group (n=30) <![CDATA[t / z / χ 2 Value]]> P-value Gender (male / female) / case 20 / 10 19 / 11 1.016 0.246 Average age (x±s) / year 67.6±44.7 68.1±5.2 1.332 0.534 <![CDATA[Average body mass index (x±s) / (kg / m 2 )]]> 25.2±1.9 26.3±2.1 3.264 0.479 Average duration of diabetes (x±s) / year 16.2±3.4 13.2±5.2 2.253 0.263 Wagner classification / case 1.458 0.546 Level 2 8 10 Level 3 9 8 Level 4 13 12

[0116] 1.2 Western Medical Diagnostic Criteria: According to the "Chinese Guidelines for the Diagnosis and Treatment of Diabetic Foot," the diagnostic criteria for diabetic foot include: a history of diabetes; intermittent claudication and rest pain; foot ulcers and gangrene; lower extremity paresthesias; trophic changes in the skin; and foot deformities. Diabetic foot is diagnosed if these conditions are met. Wagner's grading system: Grade 2—deep infection penetrating soft tissue but without osteomyelitis or deep abscesses; Grade 3—deep soft tissue ulcers with associated osteomyelitis or deep abscesses; Grade 4—ischemic gangrene with localized foot infection.

[0117] 1.3 Traditional Chinese Medicine Syndrome Differentiation Criteria: The differentiation criteria for Qi Deficiency and Blood Stasis Syndrome are formulated with reference to the TCM Syndrome Differentiation Criteria for Qi and Blood Deficiency and Blood Vessel Stasis Syndrome in Diabetic Foot Disease, as outlined in the "Guidelines for Integrated Traditional Chinese Medicine Diagnosis and Treatment of Diabetic Foot Disease." Primary symptoms include lower extremity soreness, numbness, decreased or absent sensation, intermittent claudication, pain at rest, pain resembling a needle, and prolonged wound healing. Secondary symptoms include fatigue and weakness; aversion to cold and cold extremities; lower extremity weakness; cool extremities; dry skin; and hair loss. Tongue and Pulse: Pale tongue with a white coating and a thready, wiry pulse. If the primary symptom and two secondary symptoms are present, the syndrome can be differentiated based on the tongue and pulse.

[0118] 1.4 Inclusion criteria: Patients who met the Western medical diagnostic criteria for diabetic foot and the Traditional Chinese Medicine criteria for Qi deficiency and blood stasis syndrome; Wagner grade 2-4 diabetic foot; aged 50-75 years; voluntarily participated in this study and signed the informed consent form.

[0119] 1.5 Exclusion criteria: patients with serious medical diseases; pregnant or lactating women; patients who are allergic to or have contraindications to the drugs used in the study.

[0120] 1.6 Dropout criteria: Patients who have allergic reactions or serious adverse events and the doctor judges that the trial should be stopped; patients with poor compliance and failure to take the medication on time or as designed; patients who withdraw on their own.

[0121] 2 Treatment methods

[0122] Both groups received routine dressing changes daily: routine hydrogen peroxide and iodine disinfection, followed by normal saline irrigation of the wound surface. Consult with the endocrinology department for blood sugar control, blood sugar monitoring, and adjustments to blood sugar fluctuations (pre-meal fasting blood sugar <7 mmol / L, 2-hour post-meal fasting blood sugar <11 mmol / L).

[0123] 2.1 Control Group: After routine dressing change, the wound surface was soaked with the filtrate obtained in Comparative Example 1. 1 dose per day, 500 ml per dose. Before use, heat to 40°C, soak sterile gauze with the solution, and place it on the wound surface to soak for 20 minutes. Change the gauze as it cools slightly during the soaking process.

[0124] 2.2 Experimental Group: After routine dressing change, the wound surface was soaked with the filtrate obtained in Example 1. One dose per day, 500 ml per dose. Before use, heat to 40°C, soak sterile gauze with the solution, and place it on the wound surface to soak for 20 minutes. Change the gauze as it cools slightly during the soaking process.

[0125] Patients in both groups were treated with soaking once a day after dressing change, and the course of treatment was 4 weeks.

[0126] 3. Observation of therapeutic effects

[0127] 3.1 Observation indicators

[0128] 3.1.1 Levels of inflammatory factors: Enzyme-linked immunosorbent assay (ELISA) was used to detect serum interleukin (IL)-6 and tumor necrosis factor (TNF)-α levels in the two groups of patients before and after treatment. The kits were purchased from Hangzhou Lianke Biotechnology Co., Ltd.

[0129] 3.1.2 Wound Recovery: The ulcer healing time and granulation tissue growth time of the ulcer surface were compared between the two groups. The time from the start of treatment to the wound surface being completely covered by epithelium was defined as the ulcer healing time, and the time from the start of treatment to the wound surface being covered by granulation tissue was defined as the granulation tissue growth time.

[0130] 3.2 Statistical Methods: SPSS 27.0 statistical software was used for statistical analysis. All measured data in this study conformed to a normal distribution and were expressed as mean ± standard deviation (x ± s). Within-group comparisons were performed using the paired-sample t-test, and between-group comparisons were performed using the independent-sample t-test. Enumeration data were expressed as cases or percentages and were analyzed using the chi-square test. A P value of < 0.05 was considered statistically significant.

[0131] 3.3 Treatment outcomes

[0132] 3.3.1 Comparison of inflammatory factor levels in 2 groups of patients before and after treatment

[0133] Before treatment, there were no statistically significant differences in serum TNF-α and IL-6 levels between the two groups (P>0.05). After treatment, these indicators were significantly lower in both groups compared with their pre-treatment levels (P<0.05), with the experimental group significantly lower than the control group (P<0.05). See Table 8.

[0134] Table 8 Comparison of inflammatory factor levels in the experimental and control groups before and after treatment (x±s) Unit: pg / mL

[0135]

[0136] Note: Compared with the group before treatment, #P<0.05; compared with the control group after treatment, △P<0.05.

[0137] 3.3.2 Comparison of wound recovery in 2 groups of patients

[0138] The ulcer healing time and granulation tissue growth time of the treatment group were significantly shorter than those of the control group (P<0.05). See Table 9.

[0139] Table 9 Comparison of wound recovery between the experimental group and the control group (x±s) Unit: d

[0140] Group Number of cases Ulcer healing time Ulcer surface granulation tissue growth time Experimental group 30 <![CDATA[28.14±2.36 Δ ]]> <![CDATA[13.37±1.79 Δ ]]> control group 30 37.38±4.12 19.26±1.57

[0141] Note: Compared with the control group, △P<0.05.

[0142] In summary, compared with the unimproved Chinese medicine composition of the control group, the improved Chinese medicine composition of the present invention has a significant improvement and therapeutic effect on inflammation caused by diabetic foot of qi and blood deficiency type. It can be concluded that compared with the unimproved Chinese medicine composition of the control group, the improved Chinese medicine composition of the present invention has a significant improvement and therapeutic effect on wound recovery of diabetic foot of qi and blood deficiency type.

[0143] Experimental Example 3 Clinical Treatment Case

[0144] Case 1:

[0145] Mr. Wang, a 65-year-old male, was admitted to the orthopedic outpatient clinic of Beijing Longfu Hospital on September 4, 2021, for "1-week-long gangrene on the right foot." The patient had a history of diabetes for over 10 years. A week earlier, after the skin of his foot was damaged, he tried to change the dressing at home without significant improvement. He was admitted to Beijing Longfu Hospital for systematic treatment. Physical examination showed dry gangrene on the second toe of the right foot, surrounded by a small amount of deep pus with a smell. There was also widespread redness and swelling on the dorsum of the foot, numbness of the limbs, fatigue, soreness of the waist and knees, regular bowel movements, a dark tongue, and a deep, wiry pulse. Fasting blood glucose was 11.3 mmol / L, and the sensory nerve conduction velocity of the tibial nerve was 35 m / s.

[0146] Treatment options:

[0147] The patient underwent amputation of the second toe and received routine daily dressing changes: routine disinfection with hydrogen peroxide and iodine, followed by normal saline irrigation of the wound. Consultation with the endocrinologist was required to monitor blood sugar levels and adjust for fluctuations (pre-meal fasting blood sugar <7 mmol / L, 2-hour post-meal fasting blood sugar <11 mmol / L).

[0148] After changing the dressing, use the filtrate of Example 1, once daily, taking approximately 500 mL of the juice. Heat the liquid, soak sterile gauze in the liquid, and place it on the wound surface to soak for 20 minutes. Change the gauze as it cools slightly during the soaking process. Soak once daily after changing the dressing for a course of 4 weeks.

[0149] Treatment effects:

[0150] The symptoms are now alleviated compared with before, but there is still numbness and pain in the limbs, occasional fatigue, soreness in the waist and knees, good appetite, improved sleep, regular bowel movements, deep red tongue, deep pulse, fasting blood sugar rechecked 6.7mmol / L, tibial nerve sensory nerve conduction velocity 41m / s. The patient was discharged on October 8, 2021. Fresh granulation tissue grew in the wound, the wound was stable, fasting blood sugar was 6.4mmol / L, and tibial nerve sensory nerve conduction velocity was 41m / s.

[0151] Case 2

[0152] Zhao, a 79-year-old male, was admitted to the Orthopedics Department of Beijing Longfu Hospital on October 12, 2024, for "left foot gangrene for one month". The patient had a history of diabetes for more than 20 years. One month ago, the skin of the foot was damaged and he treated it at home by changing the dressing without significant improvement. In order to seek systematic treatment, he was admitted to Beijing Longfu Hospital. Physical examination showed that the skin of the left heel was damaged, with deep pus extending to the calcaneus, with a foul odor, widespread redness and swelling on the sole of the foot, numbness of the limbs, fatigue, soreness of the waist and knees, poor appetite, only one bowel movement per day, pale tongue, and a thready and wiry pulse. Fasting blood sugar was 17.6mmol / L, and the sensory nerve conduction velocity of the tibial nerve was 34m / s.

[0153] Treatment options:

[0154] The patient underwent amputation of the second toe and received routine daily dressing changes: routine disinfection with hydrogen peroxide and iodine, followed by normal saline irrigation of the wound. Consultation with the endocrinologist was required to monitor blood sugar levels and adjust for fluctuations (pre-meal fasting blood sugar <7 mmol / L, 2-hour post-meal fasting blood sugar <11 mmol / L).

[0155] After changing the dressing, use the filtrate of Example 2, once daily, taking approximately 500 mL of the juice. Heat the liquid, soak sterile gauze in the liquid, and place it on the wound surface to soak for 20 minutes. Change the gauze as it cools slightly during the soaking process. Soak once daily after changing the dressing for a course of 4 weeks.

[0156] Treatment effects:

[0157] The symptoms are now alleviated compared with before, but there is still numbness and pain in the limbs, occasional fatigue, soreness in the waist and knees, good appetite, improved sleep, regular bowel movements, deep red tongue, deep pulse, fasting blood sugar rechecked 7.2mmol / L, tibial nerve sensory nerve conduction velocity 39m / s. The patient was discharged on December 1, 2024. Fresh granulation tissue grew in the wound, the wound was stable, fasting blood sugar was 6.7mmol / L, and tibial nerve sensory nerve conduction velocity was 42m / s.

[0158] Case 3

[0159] Mr. Li, a 72-year-old male, presented to the Orthopedics Clinic of Beijing Longfu Hospital with a history of foot gangrene for over 20 years. Two months prior, he had a broken skin on the first toe of his left foot and had been treating it at home with dressing changes, but with no significant improvement. The first toe had turned black, with purulent exudation and pain. He sought systematic treatment at Beijing Longfu Hospital. Physical examination revealed dry gangrene on the first toe of his left foot, surrounded by a small amount of deep, odorous pus, widespread redness and swelling on the dorsum of the foot, and numbness in all four limbs. His VAS score was 9, and his fasting blood sugar was 12.3 mmol / L. Regarding blood sugar control after admission, he requested a consultation with the Endocrinology Department to monitor blood sugar and adjust blood sugar fluctuations (blood sugar control: pre-meal fasting blood sugar <7 mmol / L, 2-hour post-meal fasting blood sugar <11 mmol / L).

[0160] A patient underwent amputation of the first toe. After dressing changes, the filtrate of Example 3 was applied daily, with approximately 500 mL of the solution taken. The solution was heated, and sterile gauze soaked in the solution was placed on the wound surface to soak for 20 minutes. The gauze was changed as soon as it cooled slightly during the soaking process. The wound was soaked once daily after dressing changes for a course of 4 weeks.

[0161] After 4 weeks of treatment, the VAS score was 3 points and the wound recovered well.

[0162] Case 4

[0163] On February 22, 2023, Mr. Zhao, an 81-year-old male, was admitted to the Orthopedics Department of Beijing Longfu Hospital for treatment of "left forefoot gangrene for one week". The patient had a history of diabetes for more than 10 years. One week ago, the skin of the foot was damaged and he treated it at home by changing the dressing without significant improvement. In order to seek systematic treatment, he was admitted to Beijing Longfu Hospital. Physical examination showed that the skin of the left forefoot was damaged, with deep pus extending to the heel bone, with a foul odor, widespread redness and swelling on the sole of the foot, numbness of the limbs, fatigue, soreness of the waist and knees, poor appetite, only one bowel movement per day, pale tongue, thin and wiry pulse, fasting blood sugar of 27.2mmol / L, and tibial nerve sensory nerve conduction velocity of 32m / s.

[0164] Treatment options:

[0165] The patient underwent left forefoot amputation and received routine daily dressing changes: routine hydrogen peroxide and iodine disinfection, followed by normal saline irrigation of the wound. Consultation with the endocrinologist was performed to monitor blood sugar levels and adjust for fluctuations (pre-meal fasting blood sugar <7 mmol / L, 2-hour post-meal fasting blood sugar <11 mmol / L).

[0166] After dressing change, use the filtrate of Example 4, once daily, taking approximately 500 mL of the juice. Heat the liquid, soak sterile gauze in the liquid, and place it on the wound surface to soak for 20 minutes. Change the gauze as it cools slightly during the soaking process. Soak once after each dressing change for a course of 4 weeks.

[0167] Treatment effects:

[0168] The symptoms are now alleviated compared with before, but there is still numbness and pain in the limbs, occasional fatigue, soreness in the waist and knees, good appetite, improved sleep, regular bowel movements, deep red tongue, deep pulse, fasting blood sugar 6.2mmol / L, tibial nerve sensory nerve conduction velocity 42m / s. The patient was discharged on May 12, 2023. Fresh granulation tissue grew in the wound, the wound was stable, fasting blood sugar 5.7mmol / L, tibial nerve sensory nerve conduction velocity 42m / s.

[0169] Case 5

[0170] Han, a 67-year-old male, was admitted to the Orthopedics Department of Beijing Longfu Hospital on March 23, 2022, for "gangrene on the right forefoot for 2 weeks". The patient had a history of diabetes for more than 10 years. Two weeks ago, the skin of the right forefoot was damaged and he treated it at home by changing the dressing without significant improvement. In order to seek systematic treatment, he was admitted to Beijing Longfu Hospital. Physical examination showed that the skin of the right forefoot was damaged, with deep pus extending to the calcaneus, with a foul odor, widespread redness and swelling on the sole of the foot, numbness of the limbs, fatigue, soreness of the waist and knees, poor appetite, only one bowel movement per day, pale tongue, thin and wiry pulse, fasting blood sugar of 13.5mmol / L, and tibial nerve sensory nerve conduction velocity of 31m / s.

[0171] Treatment options:

[0172] The patient underwent right forefoot amputation and received routine daily dressing changes: routine hydrogen peroxide and iodine disinfection, followed by normal saline irrigation of the wound. Consultation with the endocrinologist was performed to monitor blood sugar levels and adjust for fluctuations (pre-meal fasting blood sugar <7 mmol / L, 2-hour post-meal fasting blood sugar <11 mmol / L).

[0173] After changing the dressing, use the filtrate of Example 5, once daily, taking approximately 500 mL of the juice. Heat the liquid, soak sterile gauze with the liquid, and place it on the wound surface to soak for 20 minutes. Change the gauze as it cools slightly during the soaking process. Soak once daily after changing the dressing for a course of 4 weeks.

[0174] Treatment effects:

[0175] The symptoms are now alleviated compared with before, but there is still numbness and pain in the limbs, occasional fatigue, soreness in the waist and knees, good appetite, improved sleep, regular bowel movements, deep red tongue, deep pulse, fasting blood sugar 5.1mmol / L, tibial nerve sensory nerve conduction velocity 39m / s. The patient was discharged on July 1, 2022. Fresh granulation tissue grew in the wound, the wound was stable, fasting blood sugar 6.6mmol / L, tibial nerve sensory nerve conduction velocity 40m / s.

[0176] Case 6

[0177] On January 12, 2025, a 59-year-old male, Zhang, was admitted to the Orthopedics Department of Beijing Longfu Hospital for treatment of "1 month of gangrene on both forefeet." He had a history of diabetes for over 2 years. A month earlier, he had skin damage on both forefeet and had been treating the problem at home with dressing changes, but no significant improvement was seen. He sought systematic treatment at Beijing Longfu Hospital. Physical examination revealed skin damage on both forefeet, deep pus extending to the calcaneus, a foul odor, widespread redness and swelling on the soles of the feet, numbness in the limbs, fatigue, soreness in the waist and knees, poor appetite, only one bowel movement per day, a pale tongue, a thready and wiry pulse, fasting blood sugar of 10.6 mmol / L, and a tibial nerve sensory nerve conduction velocity of 29 m / s.

[0178] Treatment options:

[0179] The patient underwent bilateral forefoot amputation and received routine daily dressing changes: routine hydrogen peroxide and iodine disinfection, followed by normal saline irrigation of the wound surface. Consultation with the endocrinologist was also necessary to monitor blood sugar levels and adjust for fluctuations (pre-meal fasting blood sugar <7 mmol / L, 2-hour post-meal fasting blood sugar <11 mmol / L).

[0180] After changing the dressing, use the filtrate of Example 6, once daily, taking approximately 500 mL of the juice. Heat the liquid, soak sterile gauze with the liquid, and place it on the wound surface to soak for 20 minutes. Change the gauze as it cools slightly during the soaking process. Soak once daily after changing the dressing for a course of 4 weeks.

[0181] Treatment effects:

[0182] The symptoms are now alleviated compared with before, but there is still numbness and pain in the limbs, occasional fatigue, soreness in the waist and knees, good appetite, improved sleep, regular bowel movements, deep red tongue, deep pulse, fasting blood sugar rechecked 7.2mmol / L, tibial nerve sensory nerve conduction velocity 43m / s. The patient was discharged on March 28, 2025. Fresh granulation tissue grew in the wound, the wound was stable, fasting blood sugar was 6.9mmol / L, and tibial nerve sensory nerve conduction velocity was 41m / s.

[0183] Obviously, the above embodiments are merely examples for clarity of explanation and are not intended to limit the implementation methods. Those skilled in the art will readily appreciate that other variations or modifications based on the above descriptions are possible. It is not necessary and impossible to enumerate all implementation methods here. Obvious variations or modifications arising therefrom remain within the scope of protection of the present invention.

Claims

1. A Chinese medicine composition, characterized in that The medicine comprises the following raw materials: leech, Millettia reticulata, earthworm, red peony root, radix polygoni lobatae, cyperus rotundus, cassia twig, frankincense, myrrh, aconite root, angelica sinensis, rhubarb, coptis chinensis, and astragalus.

2. The Chinese medicine composition according to claim 1, characterized in that The composition is prepared from the following raw materials in parts by weight: 10-30 parts by weight of leech, 10-30 parts by weight of Millettia reticulata, 10-30 parts by weight of earthworm, 10-30 parts by weight of red peony root, 10-30 parts by weight of scutellaria baicalensis, 10-30 parts by weight of Cyathula capitata, 10-30 parts by weight of cinnamon twig, 10-30 parts by weight of frankincense, 10-30 parts by weight of myrrh, 10-30 parts by weight of aconite root, 10-30 parts by weight of angelica sinensis, 10-30 parts by weight of rhubarb, 10-30 parts by weight of coptis chinensis, and 10-30 parts by weight of astragalus.

3. A method for preparing the Chinese medicine composition according to any one of claims 1 to 2, characterized in that: include: Weigh the raw materials according to the formula, Mix and extract.

4. The method for preparing the Chinese medicine composition according to claim 3, wherein The extraction is water extraction: add 5 to 10 times the weight of water to the mixed raw materials, soak for 3 to 5 hours, heat to 60 to 80° C., maintain for 10 to 15 minutes, extract 1 to 2 times, filter, and combine the filtrates.

5. A Chinese medicine preparation, characterized in that The active ingredient comprises a traditional Chinese medicine composition prepared by the preparation method of the traditional Chinese medicine composition according to any one of claims 1 to 2 or the traditional Chinese medicine composition according to any one of claims 3 to 4.

6. The Chinese medicine preparation according to claim 5, characterized in that Pharmaceutically acceptable excipients are also included.

7. The Chinese medicine preparation according to claim 6, characterized in that The traditional Chinese medicine preparations include liquid preparations or solid preparations.

8. The Chinese medicine preparation according to claim 7, characterized in that The dosage form of the Chinese medicine preparation includes tablets, capsules, powders, granules or pastes; Optionally, the dosage form includes pills, injections, granules, powders, oral solutions, sprays, powder injections, sugar-coated tablets, film-coated tablets, enteric-coated tablets, orally disintegrating tablets, hard capsules, soft capsules, lozenges, granules, pills, pastes or disintegrants.

9. Use of the Chinese medicine composition according to any one of claims 1 to 2 or the Chinese medicine composition prepared by the method for preparing the Chinese medicine composition according to any one of claims 3 to 4 or the Chinese medicine preparation according to claim 7 or 8 in any of the following items; (1) Use in the preparation of drugs for preventing, alleviating or treating diabetic foot or its complications; (2) Use in the preparation of a drug for preventing, alleviating or treating inflammation caused by diabetic foot; (3) Use in the preparation of drugs for preventing, alleviating or treating wound healing of diabetic foot.

10. The use according to claim 9, characterized in that include: The complications include diabetic peripheral vascular disease or diabetic peripheral neuropathy; and / or, the inflammation caused by diabetic foot includes elevated serum TNF-α and IL-6 levels; And / or, the diabetic foot is diabetic foot of qi and blood deficiency type.

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