Medicine for treating vasculitis and preparation method thereof

Abstract

The invention belongs to the technical field of traditional Chinese medicines, and particularly discloses a traditional Chinese medicine composition for treating vasculitis. The medicine is mainly prepared from glutinous rice roots, gallnuts, schisandra chinensis, asarum, leeches, earthworms, kadsura pepper stems, astragalus membranaceus, golden cypress, coix seeds, angelica sinensis, notopterygium roots and radix angelicae pubescentis. Clinical verification and pharmacological analysis show that the traditional Chinese medicine composition has strong functions of resisting blood coagulation, eliminating thrombus, clearing away heat and toxic materials, diminishing inflammation and relieving pain. Pharmacological experiments prove that the traditional Chinese medicine composition can effectively reduce IL-1beta in a mouse body, relieve TAO rat vascular endothelial inflammation damage and reduce the blood coagulation risk, is definite in clinical curative effect, can control disease development, improve hematology and reduce inflammatory response, is small in toxic and side effects and has a wide market prospect.

Description

Technical Field

[0001] The invention relates to a Chinese medicine composition and a preparation method thereof, in particular to a Chinese medicine formula for treating vasculitis, and belongs to the technical field of Chinese medicine. Background Art

[0002] Chronic ischemic disease of the lower limbs is the specific manifestation of peripheral arterial disease in the lower limbs. The common clinical types mainly include thromboangiitis obliterans, diabetic foot, and lower limb arteriosclerosis obliterans.

[0003] Thromboangiitis obilterans (TAO) is a chronic, non-atherosclerotic, segmental, inflammatory, occlusive, smoking-related vascular disease, with the main pathological features of cell-rich arterial thrombosis and extensive endarteritis. As one of the chronic ischemic diseases of the lower limbs, the pathogenesis of TAO is still unclear. There are many methods for treating TAO, including smoking cessation, drug therapy, endovascular therapy, revascularization surgery, stem cell therapy, immunotherapy, bone transfer surgery, traditional Chinese medicine, and integrated Chinese and Western medicine.

[0004] Western medicine treatment: Currently, the Western medicines commonly used to treat lower extremity thromboangiitis obliterans include cilostazol and iloprost. Cilostazol has a good anti-inflammatory effect and can inhibit the expression of vascular cell adhesion molecule-1 and inflammatory factors in the plasma of patients with thromboangiitis obliterans. The combined use of aspirin can effectively improve the clinical efficacy of diabetes combined with thromboangiitis obliterans and delay the progression of thromboangiitis obliterans. Iloprost can inhibit platelet activation, reduce platelet aggregation, and prevent thrombosis, thereby preventing the deterioration of the condition of patients with thromboangiitis obliterans. However, long-term use of iloprost and cilostazol may be a risk factor for skin gangrene in patients with thromboangiitis obliterans. The use of this drug during treatment requires close observation and attention to changes in the patient's condition.

[0005] Treatment with Traditional Chinese Medicine: Thromboangiitis obliterans is classified as "gangrene" and "pulse paralysis" in traditional Chinese medicine. Its etiology and pathogenesis are relatively complex, and the onset is closely related to the viscera, qi and blood, and meridians, which is a syndrome of deficiency in the root and excess in the superficial. Li Yanyi, a famous traditional Chinese medicine doctor in China, believes that thromboangiitis obliterans is mostly caused by blood stasis and phlegm and dampness in the lower part of the body. The treatment should be based on promoting blood circulation and nourishing blood, breaking blood and removing blood stasis, drying dampness, clearing heat and resolving phlegm. The prescription she created, Foshou Sanmiao Powder (composed of: Angelica sinensis, Chuanxiong, Phellodendron chinense, Atractylodes macrocephala, Chuanxiong, Astragalus, Cinnamon twig, Red peony root, Trillium, Curcuma zedoaria, Licorice, etc.) is used to treat this disease, with significant efficacy. Academician Tong Xiaolin clinically uses the syndrome-syndrome-disease combination diagnosis and treatment system to treat this disease. First, the disease is diagnosed, then the syndrome is diagnosed. The treatment is mainly based on warming the meridians and dispersing cold, regulating qi and blood, and the classical prescription is selected to achieve certain efficacy. Tang Zuxuan, a master of traditional Chinese medicine, attributed this disease to the pathological changes of the heart, liver and kidney, and used Chinese medicine fumigation (decocting the medicine and fumigating the affected limb) to treat this disease. For the type of yang deficiency and blood stasis, the treatment is to warm the yang and activate blood circulation, and drugs such as Chuanxiong, safflower, frankincense, myrrh, angelica, cinnamon twig, and smilax glabra are selected; the type of heat toxicity is suitable for clearing away heat and detoxification, and drugs such as Coptis chinensis, rhubarb, phellodendron, dandelion, sophora flavescens, Kochia scoparia, and honeysuckle are used; for the type of qi deficiency and blood stasis and both yin and yang deficiency, drugs such as Su Mu, Chuanxiong, red peony root, safflower, Liu Jinu, Astragalus, frankincense, and myrrh are used. At present, Chinese medicine has a certain therapeutic and relieving effect on thromboangiitis obliterans, but it is difficult to cure it and it is easy to relapse. Summary of the invention

[0006] The main purpose of the present invention is to provide a new Chinese medicine composition, which has a good therapeutic effect on chronic ischemic diseases of the lower limbs.

[0007] The Chinese medicine combination of the present invention is mainly prepared from the following raw materials: glutinous rice root, gallnut, schisandra, asarum, leech, earthworm, kelp, astragalus, phellodendron, coix seed, angelica, notopterygium wilfordii and angelica pubescens.

[0008] In some embodiments, the Chinese medicine composition is mainly prepared from the following raw materials:

[0009] 80-150 weight parts of glutinous rice roots, 20-50 weight parts of gallnuts, 20-50 weight parts of Schisandra chinensis, 10-30 weight parts of asarum, 5-15 weight parts of leeches, 5-15 weight parts of earthworms, 10-20 weight parts of Kadzu vines, 20-50 weight parts of Astragalus, 20-50 weight parts of Phellodendron amurense, 20-60 weight parts of Coix seeds, 20-60 weight parts of Angelica sinensis, 20-60 weight parts of Notopterygium wilfordii, 20-50 weight parts of Duhuo pubescens, 20-50 weight parts of Angelica dahurica.

[0010] In a more preferred embodiment, the Chinese medicine composition is mainly prepared from the following raw materials:

[0011] 100 parts by weight of glutinous rice root 32 parts by weight of Chinese gallnut 32 parts by weight of Schisandra chinensis 20 parts by weight of Asarum

[0012] 10 parts by weight of leech, 8 parts by weight of earthworm, 18 parts by weight of Piper mesenteriae, 40 parts by weight of Astragalus, 44 parts by weight of Phellodendron, 43 parts by weight of Coix seeds, 42 parts by weight of Angelica sinensis, 35 parts by weight of Notopterygium wilfordii, and 29 parts by weight of Angelica dahurica.

[0013] The present invention also provides the use of the above composition in preparing a method for treating vasculitis, diabetic foot and lower limb arteriosclerosis obliterans.

[0014] In some embodiments, the vasculitis is thromboangiitis obliterans.

[0015] Another object of the present invention is to provide a method for preparing the above-mentioned composition: the raw medicinal material slices are subjected to steam distillation, water decoction, and ethanol reflux extraction to obtain an extract, the extract is dried and crushed, mixed with fine powder of animal medicinal materials, and pharmaceutically acceptable excipients are added to prepare a clinically acceptable dosage form.

[0016] In a more preferred embodiment, the preparation is prepared by the following method:

[0017] A. Weigh the prescribed amount of glutinous rice root, Chinese gallnut, Schisandra chinensis, Asarum and Chinese angelica, add water and distill for 6 to 8 hours, collect the volatile oil, and use the distilled aqueous solution and the residue for later use;

[0018] B. Weigh the prescribed amount of Astragalus, Phellodendron, Coix Seed, Notopterygium, Angelica dahurica, Caulis Piperis, and 1 / 2 of the prescribed amount of Hirudo and Pheretima, and combine them with the residue obtained in step A, add 6-12 times the amount of water and boil for 2-3 times, each time for 1-3 hours, combine the decoctions, filter and set aside; C. Combine the aqueous solution after distillation in step A with the decoction in step B, concentrate to obtain a concentrated solution, add ethanol to make the alcohol content reach 60%-70%, stand for 24-36 hours to fully precipitate, collect the supernatant, filter, and concentrate the filtrate under reduced pressure to recover ethanol to obtain an extract, vacuum dry the extract to a dry paste, and grind it into dry powder;

[0019] D. Crush the remaining 1 / 2 amount of leeches and earthworms into fine powder and set aside;

[0020] E. Mix the fine powder of medicinal material obtained in step D and the dry powder obtained in step C, add the volatile oil in step A, and prepare a clinically acceptable dosage form directly or by adding pharmaceutically acceptable excipients through conventional procedures.

[0021] According to some embodiments, the traditional Chinese medicine preparation is an oral preparation.

[0022] In a preferred embodiment, the oral preparation is a capsule, a tablet, a pill, a granule or one or more of the oral preparations.

[0023] Another object of the present invention is to provide a traditional Chinese medicine preparation, which is prepared from the above-mentioned traditional Chinese medicine composition.

[0024] Compared with the prior art, the present invention has achieved remarkable technical effects:

[0025] 1) Pharmacological experiments have shown that the Chinese medicine composition of the present invention can reduce IL-1β, alleviate vascular endothelial inflammatory damage in TAO rats, increase FIB levels, reduce 6-K-PGF1α, TT, PT, APTT levels, and reduce coagulation risk.

[0026] 2) Clinical trials have confirmed that the Chinese medicine composition of the present invention has a definite therapeutic effect in treating thromboangiitis obliterans, can control the progression of the disease, improve blood rheology, reduce inflammatory response, and has good drug safety. Specific embodiments

[0027] The present invention is further explained below in conjunction with specific examples. It should be understood that these examples are only used to illustrate the present invention and are not used to limit the scope of the present invention. After reading the present invention, various equivalent modifications of the present invention by those skilled in the art fall within the scope defined by the claims attached to this application.

[0028] Example 1: A drug for treating vasculitis and a method for preparing the drug, as follows:

[0029] 100g glutinous rice root, 32g gallnut, 32g Schisandra chinensis, 20g Asarum, 10g Leech, 8g Pheretima multiflora, 18g Piper membranaceus, 40g Astragalus, 44g Phellodendron chinense, 43g Coix seeds, 42g Angelica sinensis, 35g Notopterygium wilfordii, and 29g Duhuo.

[0030] A. Weigh the prescribed amount of glutinous rice root, Chinese gallnut, Schisandra chinensis, Asarum and Chinese angelica, add water and distill for 6 to 8 hours, collect the volatile oil, and use the distilled aqueous solution and the residue for later use;

[0031] B. Weigh the prescribed amount of Astragalus, Phellodendron, Coix Seed, Notopterygium, Angelica dahurica, Caulis Piperis, and 1 / 2 of the prescribed amount of Leech and Pheretima, and combine them with the residue obtained in step A, add 6-12 times the amount of water and boil for 2-3 times, each time for 1-3 hours, combine the decoctions, filter and set aside;

[0032] C. Combine the aqueous solution after distillation in step A and the decoction in step B, concentrate to obtain a concentrate, add ethanol to make the alcohol content reach 60%-70%, let it stand for 24-36 hours to allow it to fully precipitate, collect the supernatant, filter, concentrate the filtrate under reduced pressure to recover ethanol to obtain an extract, vacuum dry the extract to a dry paste, and grind it into dry powder;

[0033] D. Crush the remaining 1 / 2 amount of leeches and earthworms into fine powder and set aside;

[0034] E. Mix the fine powder of medicinal materials obtained in step D and the dry powder obtained in step C, add the volatile oil in step A and appropriate amount of starch, mix well, make pills, and dry.

[0035] Example 2: A drug for treating vasculitis and a method for preparing the drug, as follows:

[0036] 80g of glutinous rice root, 20g of gallnut, 20g of Schisandra chinensis, 10g of Asarum, 5g of Leech, 5g of Pheretima, 10g of Piper membranaceus, 20g of Astragalus, 20g of Phellodendron chinense, 20g of Coix seeds, 20g of Angelica sinensis, 20g of Notopterygium wilfordii, and 20g of Duhuo.

[0037] A. Weigh the prescribed amount of glutinous rice root, Chinese gallnut, Schisandra chinensis, Asarum and Chinese angelica, add water and distill for 6 to 8 hours, collect the volatile oil, and use the distilled aqueous solution and the residue for later use;

[0038] B. Weigh the prescribed amount of Astragalus, Phellodendron, Coix Seed, Notopterygium, Angelica dahurica, Caulis Piperis, and 1 / 2 of the prescribed amount of Hirudo and Pheretima, and combine them with the residue obtained in step A, add 6-12 times the amount of water and boil for 2-3 times, each time for 1-3 hours, combine the decoctions, filter and set aside; C. Combine the aqueous solution after distillation in step A with the decoction in step B, concentrate to obtain a concentrated solution, add ethanol to make the alcohol content reach 60%-70%, stand for 24-36 hours to fully precipitate, collect the supernatant, filter, and concentrate the filtrate under reduced pressure to recover ethanol to obtain an extract, vacuum dry the extract to a dry paste, and grind it into dry powder;

[0039] D. Crush the remaining 1 / 2 amount of leeches and earthworms into fine powder and set aside;

[0040] E. Take the dry powder obtained in step C and the fine powder in step D, add appropriate amount of powdered sugar and dextrin to mix, add appropriate amount of ethanol to make a soft material, granulate, dry, spray the volatile oil in step A, add the formulated amount of microcrystalline fiber and hydroxypropyl fiber (weight ratio 4:3) according to the conventional preparation process, mix, granulate, dry, add 0.2% magnesium stearate and 0.1% talcum powder, mix, tablet, and film-coat to obtain tablets.

[0041] Example 3: A drug for treating vasculitis and a method for preparing the drug, as follows:

[0042] 150g glutinous rice root, 50g gallnut, 50g Schisandra, 30g Asarum, 15g Leech, 15g Pheretima, 20g Piper membranaceus, 50g Astragalus, 60g Phellodendron, 60g Coix seeds, 60g Angelica, 50g Notopterygium, and 50g Duhuo.

[0043] A. Weigh the prescribed amount of glutinous rice root, Chinese gallnut, Schisandra chinensis, Asarum and Chinese angelica, add water and distill for 6 to 8 hours, collect the volatile oil, and use the distilled aqueous solution and the residue for later use;

[0044] B. Weigh the prescribed amount of Astragalus, Phellodendron, Coix Seed, Notopterygium, Angelica dahurica, Caulis Piperis, and 1 / 2 of the prescribed amount of Leech and Pheretima, and combine them with the residue obtained in step A, add 6-12 times the amount of water and boil for 2-3 times, each time for 1-3 hours, combine the decoctions, filter and set aside;

[0045] C. Combine the aqueous solution after distillation in step A and the decoction in step B, concentrate to obtain a concentrate, add ethanol to make the alcohol content reach 60%-70%, let it stand for 24-36 hours to allow it to fully precipitate, collect the supernatant, filter, concentrate the filtrate under reduced pressure to recover ethanol to obtain an extract, vacuum dry the extract to a dry paste, and grind it into dry powder;

[0046] D. Crush the remaining 1 / 2 amount of leeches and earthworms into fine powder and set aside;

[0047] E. Add appropriate amount of starch, micro-powder silica gel and low-substituted hydroxypropyl cellulose to the cyclodextrin inclusion compound of step A, the dry powder of step C and the fine powder of step D, mix well, granulate, dry, granulate, fill, polish in a grinder, remove damaged capsules, and obtain capsules.

[0048] Example 4: A drug for treating vasculitis and a method for preparing the drug, as follows:

[0049] 50g glutinous rice root, 10g gallnut, 10g schisandra, 5g asarum, 3g leech, 3g earthworm, 5g sea wind vine, 10g astragalus, 10g phellodendron, 10g coix seed, 10g angelica, 10g notopterygium, and 10g duhuo.

[0050] The steps are the same as in Example 1.

[0051] Example 5: A drug for treating vasculitis and a method for preparing the drug, as follows:

[0052] 200g glutinous rice root, 60g gallnut, 60g Schisandra, 50g Asarum, 20g Leech, 20g Earthworm, 30g Piper mesenteriae, 80g Astragalus, 80g Phellodendron, 80g Coix seeds, 80g Angelica, 60g Notopterygium, and 60g Duhuo.

[0053] The steps are the same as in Example 1.

[0054] Comparative Example 1

[0055] 40g of glutinous rice root, 80g of gallnut, 80g of Schisandra chinensis, 20g of Asarum, 10g of Leech, 8g of Pheretima, 3g of Piper membranaceus, 40g of Astragalus, 44g of Phellodendron chinense, 43g of Coix seeds, 42g of Angelica sinensis, 70g of Notopterygium wilfordii, and 10g of Angelica dahurica.

[0056] The steps are the same as in Example 1.

[0057] Comparative Example 2: A drug for treating vasculitis and a preparation method thereof, as follows:

[0058] 100g glutinous rice root, 32g gallnut, 32g Schisandra chinensis, 50g Asarum, 2g Leech, 2g Earthworm, 50g Piper mesenteriae, 90g Astragalus, 44g Phellodendron, 90g Coix seeds, 42g Angelica sinensis, 35g Notopterygium wilfordii, and 29g Duhuo.

[0059] The prescription amount of glutinous rice root, gallnut, schisandra, asarum, angelica, kadura strychnos, asarum, astragalus, phellodendron, coix seed, notopterygium, leech, and earthworm is weighed and combined with the residue obtained in step A, 6-12 times the amount of water is added and boiled for 2-3 times, each time for 1-3 hours, the decoction is combined, filtered and set aside; ethanol is added to the decoction in step A to make the alcohol content reach 60%-70%, the decoction is allowed to stand for 24-36 hours to fully precipitate, the supernatant is collected, filtered, the filtrate is concentrated under reduced pressure to recover ethanol to obtain an extract, the extract is vacuum dried to a dry paste, and crushed into dry powder, an appropriate amount of starch is added, mixed evenly, pilled, and dried.

[0060] Comparative Example 3: A drug for treating vasculitis and a preparation method thereof, as follows:

[0061] Floating wheat 100g, asparagus 32g, schisandra 32g, asarum 20g, leech 10g, earthworm 8g, kelp 18g, astragalus 40g, phellodendron 44g, coix seed 43g, angelica 42g, angelica 35g, and pubescens 29g.

[0062] The steps are the same as in Example 1.

[0063] Comparative Example 4: A drug for treating vasculitis and a preparation method thereof, as follows:

[0064] 100g glutinous rice root, 32g gallnut, 32g Schisandra chinensis, 20g Chuanxiong, 10g leech, 8g earthworm, 18g Piper mesenteriae, 40g Astragalus, 44g Phellodendron, 43g Coix seeds, 42g Angelica sinensis, 35g Notopterygium wilfordii, and 29g Duhuo.

[0065] The steps are the same as in Example 1.

[0066] Comparative Example 5: A drug for treating vasculitis and a preparation method thereof, as follows:

[0067] 100g glutinous rice root, 32g gallnut, 32g Schisandra chinensis, 20g Asarum, 10g Leech, 8g Pheretima, 18g Piper mesenteriae, 44g Phellodendron, 43g Poria, 42g Angelica sinensis, 35g Notopterygium wilfordii, and 29g Duhuo.

[0068] The steps are the same as in Example 1.

[0069] Comparative Example 6: A drug for treating vasculitis and a preparation method thereof, as follows:

[0070] 100g glutinous rice root, 32g gallnut, 32g Schisandra chinensis, 20g Asarum, 10g Leech, 8g Pheretima multiflora, 18g Piper membranaceus, 40g Astragalus, 44g Phellodendron chinense, 43g Coix seeds, 42g Angelica sinensis, 35g Notopterygium wilfordii, and 29g Duhuo.

[0071] The steps are the same as in Example 1.

[0072] Pharmacodynamic validation

[0073] In order to verify the effect of the Chinese medicine composition of the present invention in treating vasculitis, the inventor selected the drugs obtained in some embodiments of the present invention to carry out relevant pharmacodynamic tests and clinical studies. The inventor also conducted pharmacodynamic experiments on the drugs obtained by other formulas and preparation methods included in the present invention. The experimental results show that the drugs obtained by other formulas and preparation methods have the same or similar effects, but due to space limitations, they are not listed here one by one.

[0074] The inventors would like to explain that the following experimental studies were conducted on the basis of acute toxicity tests and long-term toxicity tests to prove the safety of the drugs. The dosages used in the experimental studies were all within the safe dosage range. The animal modeling methods and the selection of detection indicators in the following experimental studies referred to the existing literature related to animal modeling.

[0075] 1. Study on the therapeutic effect of vasculitis in rats

[0076] 1. Materials

[0077] 1 Experimental animals

[0078] SPF male Wistar rats, 180-220 g, with production license number SCXK(Lu)2022 0006, were provided by Jinan Pengyue Experimental Animal Breeding Co., Ltd. and were adaptively raised for one week before the experiment.

[0079] 2 Experimental drugs

[0080] Positive control: Vascular Fukang Tablets (Tianjin **** Co., Ltd.)

[0081] The present invention: the pills prepared in Examples 1-3 and Comparative Examples 1-6

[0082] The medicinal materials and preparations used are commonly available on the market, and the product quality complies with national regulations.

[0083] (II) Methods

[0084] 1 Modeling, grouping and drug administration

[0085] 96 rats were randomly divided into a blank group, a model group, a positive control group, Example 1, 2, 3 groups, and Comparative Example 1, 2, 3, 4, 5, 6 groups, 8 rats in each group, and adaptively fed for one week.

[0086] The TAO model was constructed. The rats were anesthetized and fixed in the supine position. A longitudinal incision was made from the midpoint of the left lower limb groin to the inner side of the knee. The proximal end of the femoral artery was clamped with an artery clamp. The proximal end of the femoral artery was clamped with a self-clip. Sodium laurate solution was injected from the distal end of the artery clamp and the needle was removed. After 15 minutes, the artery clamp was removed. The incision could be sutured if there was no active bleeding in the blood vessels. Penicillin was injected intraperitoneally after surgery. On the day of modeling, the affected paws of the rats were pale or cyanotic. The next day, the affected paws turned black and had a tendency to gangrene or mummification, proving that the modeling was successful. In the sham operation group, sodium laurate was replaced with 0.9% NaCl. The model was formed for 7 days, and drug administration began 7 days later. The positive group rats were gavaged with 1.872 g / kg of Vascular Fukang Tablets aqueous solution, the examples 1-3 and comparative examples 1-6 were gavaged with an equal amount of drug solution (raw drug amount was 1.872 g / kg), and the model group and the blank group were gavaged with an equal volume of sterile saline, once a day, for 14 consecutive days.

[0087] 2 Index determination

[0088] After the remaining 6 rats in each group were anesthetized, blood from the abdominal aorta was collected using sodium citrate anticoagulation tubes and sodium heparin anticoagulation tubes for testing.

[0089] 2.1 Determination of blood routine indicators

[0090] The fully automatic biochemical analyzer detects the levels of white blood cells, neutrophils, lymphocytes, platelets and red blood cells in the above anticoagulation tube whole blood.

[0091] 2.2 Determination of coagulation and fibrinolysis related indicators

[0092] The blood in the sodium citrate anticoagulation tube was centrifuged and the upper plasma was collected. The thrombin time (TT), prothrombin time (PT), activated partial thromboplastin time (APTT) and fibrinogen (FIB) levels were detected by magnetic bead coagulation method on a fully automatic coagulometer.

[0093] 2.3 Enzyme-linked immunosorbent assay (ELISA) kit to detect inflammatory factors and coagulation factors

[0094] The blood in the sodium heparin anticoagulation tube was centrifuged, and the upper plasma was taken. The levels of interleukin (IL)-1β and 6-keto-prostagland (66-K-PGF1α) in the plasma were detected using ELISA kits.

[0095] 3 Data processing

[0096] The data were processed using SPSS 22.0 software. The differences were statistically significant when P < 0.05.

[0097] (III) Results

[0098] 1 Comparison of blood routine indexes in rats of each group

[0099] Table 1 Comparison of blood routine indexes of rats in each group (n=8, )

[0100]

[0101] Compared with the blank group ！ P<0.05, ￥ P<0.01

[0102] Compared with the model group @ P<0.05, # P<0.01

[0103] Positive control group $ P<0.05, ^ P<0.01

[0104] Example 1 & P<0.05, * P<0.01

[0105] Compared with the blank group, the model group had statistically significant differences (P < 0.05). Compared with the model group, the vascular rehabilitation tablets and Example 1-3 groups had statistically significant differences (P < 0.05). Compared with the blank group and the positive control group, there was no significant difference (P > 0.05). Compared with Example 1 group, the comparative example 1-6 groups had statistically significant differences (P < 0.05).

[0106] 2. Coagulation and fibrinolysis related indicators of rats in each group

[0107] Table 2 Coagulation and fibrinolysis related indicators of rats in each group (n=8, )

[0108] Grouping TT(s) PT(s) APTT(s) <![CDATA[FIB(g·L -1 )]]> Blank Group 17.25±0.72 13.90±0.63 29.35±1.03 3.01±0.74 Model Group <![CDATA[11.99±0.50 ￥ ]]> <![CDATA[7.67±0.54 ￥ ]]> <![CDATA[18.29±1.40 ￥ ]]> <![CDATA[6.13±0.61 ￥ ]]> Vascular Fukang Tablets <![CDATA[13.19±0.41 @ ]]> <![CDATA[8.97±0.47 @ ]]> <![CDATA[23.70±1.29 # ]]> <![CDATA[3.76±0.45 # ]]> Example 1 Group <![CDATA[13.12±0.30 @ ]]> <![CDATA[9.17±0.55 # ]]> <![CDATA[23.06±1.09 # ]]> <![CDATA[3.82±0.51 # ]]> Example 2 Group <![CDATA[13.32±0.43 @ ]]> <![CDATA[8.92±0.38 @ ]]> <![CDATA[23.24±1.74 # ]]> <![CDATA[4.08±0.47 @ ]]> Example 3 Group <![CDATA[13.23±0.40 @ ]]> <![CDATA[9.02±0.50 @ ]]> <![CDATA[23.41±1.24 # ]]> <![CDATA[3.93±0.48 # ]]> Comparative Example 1 <![CDATA[14.83±0.57 $& ]]> <![CDATA[10.88±0.43 $& ]]> <![CDATA[26.64±1.44 $& ]]> <![CDATA[5.05±0.60 $& ]]> Comparative Example 2 <![CDATA[14.96±0.63 $& ]]> <![CDATA[10.80±0.73 $& ]]> <![CDATA[26.35±1.39 $& ]]> <![CDATA[4.86±0.39 $& ]]> Comparative Example 3 <![CDATA[14.85±0.63 $& ]]> <![CDATA[10.74±0.52 $& ]]> <![CDATA[25.99±1.32 $& ]]> <![CDATA[4.95±0.50 $& ]]> Comparative Example 4 <![CDATA[14.52±0.52 $& ]]> <![CDATA[10.79±0.47 $& ]]> <![CDATA[26.36±1.45 $& ]]> <![CDATA[4.91±0.43 $& ]]> Comparative Example 5 <![CDATA[14.73±0.54 $& ]]> <![CDATA[10.83±0.52 $& ]]> <![CDATA[26.58±1.61 $& ]]> <![CDATA[5.18±0.40 $& ]]> Comparative Example 6 <![CDATA[14.69±0.59 $& ]]> <![CDATA[10.95±0.65 $& ]]> <![CDATA[26.88±1.38 $& ]]> <![CDATA[5.03±0.47 $& ]]>

[0109] Compared with the blank group ！ P<0.05, ￥ P<0.01

[0110] Compared with the model group @ P<0.05, # P<0.01

[0111] Positive control group $ P<0.05, ^ P<0.01

[0112] Example 1 & P<0.05, * P<0.01

[0113] Compared with the blank group, the model group had statistically significant differences (P < 0.05). Compared with the model group, the vascular rehabilitation tablets and Example 1-3 groups had statistically significant differences (P < 0.05). Compared with the blank group and the positive control group, there was no significant difference (P > 0.05). Compared with Example 1 group, the comparative example 1-6 groups had statistically significant differences (P < 0.05).

[0114] Comparison of plasma inflammatory factors and coagulation factor levels in rats of 3 groups

[0115] Table 3 Comparison of plasma inflammatory factors and coagulation factor levels in each group (n=8, )

[0116] Grouping <![CDATA[IL-1β(pg,mL -1 )]]> <![CDATA[ET-1(pg,mL -1 )]]> <![CDATA[6-K-PGF1α(pg,mL -1 )]]> Blank Group 202.09±13.22 7.90±1.14 35.87±3.20 Model Group <![CDATA[401.75±15.20 ￥ ]]> <![CDATA[16.83±0.99 ￥ ]]> <![CDATA[20.69±2.31 ￥ ]]> Vascular Fukang Tablets <![CDATA[275.59±27.37 @ ]]> <![CDATA[11.45±1.44 # ]]> <![CDATA[25.28±1.18 @ ]]> Example 1 Group <![CDATA[272.85±18.02 @ ]]> <![CDATA[10.94±0.86 # ]]> <![CDATA[24.91±1.54 @ ]]> Example 2 Group <![CDATA[279.47±24.28 @ ]]> <![CDATA[11.49±1.05 # ]]> <![CDATA[25.80±1.75 @ ]]> Example 3 Group <![CDATA[283.31±26.23 @ ]]> <![CDATA[11.59±0.96 # ]]> <![CDATA[25.69±1.70 @ ]]> Comparative Example 1 <![CDATA[361.50±24.24^ * ]]> <![CDATA[14.39±0.93 $& ]]> <![CDATA[31.12±2.87 $& ]]> Comparative Example 2 <![CDATA[367.25±22.13^ * ]]> <![CDATA[14.67±0.81 $& ]]> <![CDATA[30.62±2.42 $& ]]> Comparative Example 3 <![CDATA[351.79±26.05 $& ]]> <![CDATA[14.64±0.65 $& ]]> <![CDATA[31.27±1.38 $& ]]> Comparative Example 4 <![CDATA[358.49±19.86 $& ]]> <![CDATA[14.49±0.93 $& ]]> <![CDATA[30.86±1.22 $& ]]> Comparative Example 5 <![CDATA[365.47±25.67^ * ]]> <![CDATA[14.71±0.76 $& ]]> <![CDATA[30.98±1.94 $& ]]> Comparative Example 6 <![CDATA[353.83±25.37 $* ]]> <![CDATA[14.30±1.00 $& ]]> <![CDATA[31.89±2.40 $& ]]>

[0117] Compared with the blank group ！ P<0.05, ￥ P<0.01

[0118] Compared with the model group @ P<0.05, # P<0.01

[0119] Positive control group $ P<0.05, ^ P<0.01

[0120] Example 1 & P<0.05, * P<0.01

[0121] Compared with the blank group, the model group had statistically significant differences (P < 0.05). Compared with the model group, the vascular rehabilitation tablets and Example 1-3 groups had statistically significant differences (P < 0.05). Compared with the blank group and the positive control group, there was no significant difference (P > 0.05). Compared with Example 1 group, the comparative example 1-6 groups had statistically significant differences (P < 0.05).

[0122] ET-1 is an effective vasoconstrictor peptide, and IL-1β is a factor that promotes endothelial cell damage and can induce cells to produce harmful substances and cause damage or death. The Chinese medicine composition of the present invention can reduce IL-1β and alleviate vascular endothelial inflammatory damage in TAO rats. Under normal conditions, the secretion and metabolism of thromboxane A2 and prostaglandin I2 are in dynamic equilibrium.

[0123] Blood-anticoagulation function checks and balances each other. In this study, the FIB level of TAO rats increased, and the levels of 6-K-PGF1α, TT, PT, and APTT decreased, which indicated the risk of thrombosis. The intervention of the Chinese medicine composition of the present invention can reduce the risk of coagulation.

[0124] 2. Clinical efficacy trials

[0125] 1 Patient

[0126] According to the diagnostic criteria for thrombophlebitis in the Diagnosis and Treatment of Peripheral Vascular Diseases in Traditional Chinese and Western Medicine, 152 patients with thromboangiitis obliterans were selected in 2021. Among them, 105 were male and 47 were female; the age ranged from 40 to 75 years, and the course of disease ranged from 2 to 18 years. The affected parts included 80 cases on the left side and 72 cases on the right side; the clinical stages were divided into stage I (64 cases) and stage II (88 cases).

[0127] 2 Treatment methods

[0128] Control group: Oral aspirin, antibiotics, nonsteroidal anti-inflammatory drugs, vitamin C were given in the acute phase, and compound rutin tablets, Panax notoginseng total glycosides tablets were given in the chronic phase.

[0129] Treatment group: Based on the control group, the Chinese medicine preparation obtained in Example 1-3 was taken with warm water, 5 g each time, twice a day; 15 days was a course of treatment, and the next course of treatment was carried out after an interval of 5 days.

[0130] 3 Evaluation indicators

[0131] 3.1 Clinical efficacy evaluation criteria

[0132] Efficacy standard: formulated with reference to "Diagnosis and Treatment of Peripheral Vascular Diseases with Traditional Chinese and Western Medicine".

[0133] Cure: local redness, swelling, heat, pain and hard cord-like objects disappear, no pigmentation, body temperature and white blood cells return to normal, no recurrence within 1 year;

[0134] Significantly effective: Swelling and pain disappeared, the cord-like substance was not completely absorbed, there was pigmentation, and there was no recurrence within half a year;

[0135] Ineffective: The above symptoms and signs remain unchanged, or recur repeatedly.

[0136] Total effective rate = (cured cases + markedly effective cases) / total cases

[0137] 3.2 Observation Index

[0138] 3.2.1 Ankle-brachial index

[0139] Yongkang Medical YK-8000B ECG monitor was used to measure the patients' brachial artery and posterior tibial artery before and after treatment.

[0140] The systolic blood pressure of the arteries was measured and the ankle-brachial index (ABI) was calculated.

[0141] ABI = posterior tibial artery systolic pressure at ankle / brachial artery systolic pressure

[0142] 3.2.2 Maximum walking distance

[0143] Before and after treatment, all patients tested their maximum walking distance on a Jinyu JY-PAT-5 medical treadmill with a speed set at 2000 m / h and a slope of 0°.

[0144] 3.2.3 Hemorheology indexes

[0145] The hemorheological parameters of patients before and after treatment were measured using Zibo Hengtuo HT-100G hemorheology instrument, including fibrinogen (FIB), plasma viscosity (PV), and red blood cell deformation index (DI).

[0146] 3.2.4 Adverse reaction observation

[0147] During the treatment period, the occurrence of drug-related adverse reactions such as nausea, vomiting, loss of appetite, headache, and diarrhea were recorded.

[0148] 4 Data processing

[0149] The data were processed using SPSS 22.0 software. The data were compared between the groups using the t test. P < 0.05 indicated that the difference was statistically significant.

[0150] 5 Results

[0151] 5.1 Comparison of clinical efficacy between the two groups

[0152] After treatment, the total effective rate of the treatment group was 89.47%, which was significantly higher than that of the control group (76.32%) (P < 0.05), as shown in Table 4.

[0153] Table 4 Comparison of total effective rate between the two groups

[0154] Group n / example Cured / case Significantly effective / case Invalid / Example Total effective rate / % Control group 76 36 22 18 76.32 Treatment Group 76 41 27 8 89.47

[0155] 5.2 Comparison of ABI and maximum walking distance between the two groups

[0156] After treatment, the ABI and maximum walking distance of the two groups were significantly higher than those before treatment (P < 0.05); after treatment, the ABI and maximum walking distance of the treatment group were significantly higher than those of the control group (P < 0.05), see Table 5.

[0157] Table 5 Comparison of ABI and maximum walking distance between the two groups

[0158]

[0159] Compared with the same group before treatment, @ P<0.05, compared with the control group after treatment, # P<0.05

[0160] 5.3 Comparison of blood rheology parameters between the two groups

[0161] After treatment, the FIB and PV of the two groups were lower than those before treatment, and the DI was higher than that before treatment (P < 0.05); after treatment, the FIB and PV of the treatment group were lower than those of the control group, and the DI was higher than that of the control group (P < 0.05), see Table 6.

[0162] Table 6 Comparison of FIB, PV and DI between the two groups

[0163]

[0164]

[0165] Compared with the same group before treatment, @ P<0.05, compared with the control group after treatment, # P<0.05

[0166] 5.4 Comparison of adverse events between the two groups

[0167] The incidence of adverse reactions in the control group and the treatment group were 4.88% and 7.32%, respectively, with no significant difference between the groups (see Table 7).

[0168]

Claims

1. Use of a Chinese medicine composition containing glutinous rice root, gallnut, schisandra, asarum, leech, earthworm, kadzu vine, astragalus, phellodendron, coix seed, angelica, notopterygium wilfordii and angelica pubescens in preparing a drug for treating chronic ischemic diseases of the lower limbs.

2. The use according to claim 1, characterized in that The traditional Chinese medicine composition is mainly prepared from the following raw materials: 80-150 weight parts of glutinous rice roots, 20-50 weight parts of gallnuts, 20-50 weight parts of Schisandra chinensis, 10-30 weight parts of asarum, 5-15 weight parts of leeches, 5-15 weight parts of earthworms, 10-20 weight parts of Kadzu vines, 20-50 weight parts of Astragalus, 20-50 weight parts of Phellodendron amurense, 20-60 weight parts of Coix seeds, 20-60 weight parts of Angelica sinensis, 20-60 weight parts of Notopterygium wilfordii, 20-50 weight parts of Duhuo pubescens, 20-50 weight parts of Angelica dahurica.

3. The use according to claim 2, characterized in that The traditional Chinese medicine composition is mainly prepared from the following raw materials: 100 parts by weight of glutinous rice root, 32 parts by weight of gallnut, 32 parts by weight of Schisandra chinensis, 20 parts by weight of asarum, 10 parts by weight of leech, 8 parts by weight of Phellodendron chinense, 18 parts by weight of Kadzu vine, 40 parts by weight of Astragalus, 44 parts by weight of Phellodendron amurense, 43 parts by weight of Coix seed, 42 parts by weight of Angelica sinensis, 35 parts by weight of Notopterygium wilfordii, 29 parts by weight of Duhuo pubescens.

4. The use according to any one of claims 1-3, characterized in that The chronic ischemic diseases of the lower limbs include vasculitis, diabetic foot, and arteriosclerosis occlusion of the lower limbs.

5. The use according to claim 4, characterized in that The vasculitis described is thromboangiitis obliterans.

6. A preparation containing the traditional Chinese medicine composition according to any one of claims 1-3, characterized in that The preparation is prepared by the following method: the raw medicinal material slices are subjected to steam distillation, water decoction, and ethanol reflux extraction to obtain an extract, the extract is dried and crushed, mixed with fine powder of animal medicinal materials, and pharmaceutically acceptable excipients are added to prepare a clinically acceptable dosage form.

7. The formulation of claim 6, characterized in that The preparation is prepared by the following method: A. Weigh the prescription amount of glutinous rice roots, gulfonatum, Schisandra, asarum, and Angelica, add water to distillate and extract for 6 to 8 hours, collect volatile oil, and set the distilled aqueous solution and medicine residue for later use; B. Weigh the prescribed amount of Astragalus, Phellodendron, Coix Seed, Notopterygium, Angelica dahurica, Caulis Piperis, and 1 / 2 of the prescribed amount of Leech and Pheretima, and combine them with the residue obtained in step A, add 6-12 times the amount of water and boil for 2-3 times, each time for 1-3 hours, combine the decoctions, filter and set aside; C. Combine the aqueous solution after distillation in step A and the decoction in step B, concentrate to obtain a concentrate, add ethanol to make the alcohol content reach 60%-70%, let it stand for 24-36 hours to allow it to fully precipitate, collect the supernatant, filter, concentrate the filtrate under reduced pressure to recover ethanol to obtain an extract, vacuum dry the extract to a dry paste, and grind it into dry powder; D. Crush the other 1 / 2 of the prescription amount of leeches and earth dragons into fine powder and set aside; E. Mix the fine powder of medicinal materials obtained in step D and the dry powder obtained in step C, add the volatile oil of step A, and directly or add pharmaceutically acceptable excipients to make a clinically acceptable dosage form through conventional processes.

8. The formulation of claim 7, characterized in that The preparation is an oral preparation.

9. The formulation of claim 8, characterized in that The oral preparation is one or more of capsules, tablets, pills, granules or oral preparations.

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