WO2024061140A1 - Traditional chinese medicine composition for treating immune vasculitis and formulation and use thereof - Google Patents

Abstract

A traditional Chinese medicine composition for treating immune vasculitis, prepared from 15-40 parts of radix rehmanniae, 10-20 parts of radix paeoniae rubra, 10-40 parts of fructus gardeniae, 15-60 parts of gypsum, 15-40 parts of sedum sarmentosum, 15-40 parts of solanum lyratum, 15-40 parts of oldenlandia diffusa, 15-40 parts of cornu bubali, 10-20 parts of fructus forsythiae, 6-20 parts of fried rheum officinale, 3-15 parts of liquorice, 0.6-2.4 parts of antelope horn, 3-12 parts of amber powder, and 2-8 parts of Panax notoginseng powder. The traditional Chinese medicine composition may be prepared into a decoction, a granule, a pulvise, a capsule, a tablet, or an oral liquid. The immune vasculitis disease is selected from nodular vasculitis, aorto-arteritis, thromboangiitis obliterans, rheumatoid vasculitis, systemic lupus erythematosus vasculitis, scleroderma vasculitis, or ACNA-related vasculitis.

Description

A traditional Chinese medicine composition for treating immune vasculitis and its preparation and application Technical field

The invention belongs to the technical field of traditional Chinese medicine, and specifically relates to a traditional Chinese medicine composition for treating immune vasculitis and its preparation and application.

Background technique

Immune vasculitis refers to inflammatory changes in the blood vessel wall and surrounding tissue on histopathology. In severe cases, thrombosis or even destruction of the entire blood vessel may occur, leading to hemorrhagic and/or ischemic lesions, and ultimately tissue necrosis or infarction. Immune vasculitis diseases are not uncommon in clinical practice. Research results show that the annual incidence rate is 39.6/million to 59.8/million. Immune vasculitis diseases mainly include Takayasu arteritis, giant cell arteritis, polyarteritis nodosa, ANCA-associated vasculitis, granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis, and cryoglobulin vasculitis , Division I A vasculitis, variant vasculitis, thromboangiitis obliterans, systemic lupus erythematosus-associated vasculitis, rheumatoid arthritis-associated vasculitis, scleroderma vasculitis, sarcoidosis-associated vasculitis Yan et al. At present, the treatment methods for different types of immune vasculitis are similar, either using hormone therapy or immunosuppressants, but the treatment effect is still not ideal, and hormones and immunosuppressants have serious side effects. Therefore, the development of therapeutic drugs for immune vasculitis is still the focus and difficulty of current research.

Contents of the invention

The purpose of the present invention is to provide a traditional Chinese medicine composition for treating immune vasculitis and its preparation and application.

The first aspect of the invention provides a traditional Chinese medicine composition for treating immune vasculitis, which is made from the following raw materials by weight: 15 to 40 parts of raw rehmannia root, 10 to 20 parts of red peony root, and 10 to 40 parts of gardenia jasminoides. 15 to 60 portions of gypsum, 15 to 40 portions of Astragalus, 15 to 40 portions of Diphylla japonica, 15 to 40 portions of Hedyotis diffusa, 15 to 40 portions of buffalo horn, 10 to 20 portions of Forsythia suspensa, and 6 to 6 portions of fried rhubarb. 20 parts, 3 to 15 parts of licorice, 0.6 to 2.4 parts of antelope horn, 3 to 12 parts of amber powder, and 2 to 8 parts of Panax notoginseng powder.

In a preferred example, the Chinese medicine composition is made of the following raw materials in parts by weight: 30 parts of raw rehmannia, 15 parts of red peony root, 15 parts of gardenia, 30 parts of gypsum, 30 parts of creeping cyperus, 30 parts of white peony root, 30 parts of oldenlandia diffusa, 30 parts of buffalo horn, 15 parts of forsythia, 12 parts of stir-fried rhubarb, 9 parts of licorice, 1.2 parts of antelope horn, 6 parts of amber powder, and 4 parts of Panax notoginseng powder.

In another preferred example, the traditional Chinese medicine composition is made of the following raw materials by weight: 20 parts of Rehmannia glutinosa, 10 parts of Radix Paeoniae Alba, 20 parts of Gardenia, 20 parts of Gypsum, 20 parts of Trichoderma spp. 20 parts, 20 parts of Hedyotis diffusa, 20 parts of buffalo horn, 10 parts of forsythia, 6 parts of fried rhubarb, 3 parts of licorice, 0.6 parts of antelope horn, 3 parts of amber powder, 2 parts of Panax notoginseng powder.

In another preferred example, the traditional Chinese medicine composition is made of the following raw materials by weight: 25 parts of Rehmannia glutinosa, 13 parts of Radix Paeoniae Alba, 25 parts of Gardenia jasminoides, 25 parts of Gypsum Gypsum, 25 parts of Trichosanthes kirilowii, and White Ying. 25 parts, 25 parts of Hedyotis diffusa, 25 parts of buffalo horn, 13 parts of Forsythia suspensa, 9 parts of fried rhubarb, 6 parts of licorice, 0.9 parts of antelope horn, 4.5 parts of amber powder, 3 parts of Panax notoginseng powder.

In another preferred example, the traditional Chinese medicine composition is made of the following raw materials by weight: 35 parts of Rehmannia glutinosa, 17 parts of Radix Paeoniae Alba, 35 parts of Gardenia jasminoides, 45 parts of Gypsum officinalis, 35 parts of Trichosanthes kirilowii, and Bai Yingying. 35 parts, 35 parts of Hedyotis diffusa, 45 parts of buffalo horn, 17 parts of forsythia, 12 parts of fried rhubarb, 12 parts of licorice, 1.8 parts of antelope horn, 9 parts of amber powder, 6 parts of notoginseng powder.

In another preferred example, the traditional Chinese medicine composition is made of the following raw materials by weight: 40 parts of Rehmannia glutinosa, 20 parts of Radix Paeoniae Alba, 40 parts of Gardenia jasminoides, 60 parts of Gypsum gypsum, 40 parts of Trichosanthes kirilowii, and White Yingma. 40 parts, 40 parts of Hedyotis diffusa, 40 parts of buffalo horn, 20 parts of forsythia, 20 parts of fried rhubarb, 15 parts of licorice, 2.4 parts of antelope horn, 12 parts of amber powder, 8 parts of notoginseng powder.

The second aspect of the present invention is to provide a traditional Chinese medicine compound preparation for the treatment of immune vasculitis. The traditional Chinese medicine compound preparation is a decoction, granule, powder, capsule, tablet or tablet with the above-mentioned traditional Chinese medicine composition as the active ingredient. Oral liquid.

In a preferred embodiment, the traditional Chinese medicine compound preparation is a decoction.

The present invention also provides the use of the above-mentioned traditional Chinese medicine composition in the preparation of medicines for treating immune vasculitis diseases. The immune vasculitis diseases are selected from the group consisting of nodular vasculitis, Takayasu arteritis, thromboangiitis obliterans, Rheumatoid vasculitis, systemic lupus erythematosus vasculitis, scleroderma vasculitis, or ACNA phase associated vasculitis.

In a preferred embodiment, the immune vasculitis disease is selected from the group consisting of nodular vasculitis, Takayasu arteritis, thromboangiitis obliterans, rheumatoid vasculitis, systemic lupus erythematosus vasculitis, and scleroderma vasculitis. inflammation or ACNA-associated vasculitis.

Details of various aspects of the invention are described in detail in subsequent chapters. The features, objects and advantages of the present invention will be more apparent through the following description and claims.

Description of the drawings

Figure 1 Traditional Chinese medicine composition significantly improves lower limb necrosis in rats NC is the normal group; MOD is the model group; LXHY is the traditional Chinese medicine composition group

Figure 2 The traditional Chinese medicine composition significantly increases the blood flow of the lower limbs of rats with immune vasculature. 2a is a typical picture, and 2b is a quantitative result. NC is the normal group; MOD is the model group; LXHY is the traditional Chinese medicine composition group*, compared with the normal group, P＜0.05; #, compared with the model group, P＜0.05

Figure 3 The traditional Chinese medicine composition has no obvious toxicity to the heart, liver and kidneys. NC is the normal group; MOD is the model group; LXHY is the traditional Chinese medicine composition group.

Figure 4 Chinese medicine composition significantly reduces the infiltration of inflammatory cells. NC is the normal group; MOD is the model group; LXHY is the Chinese medicine composition group; WXF is the literature prescription *, compared with the normal group, P < 0.05; #, compared with the model group Compared with the literature, P<0.05; △, compared with the literature, P<0.05

Figure 5 Traditional Chinese medicine composition significantly improves elastic fiber lesions. NC is the normal group; MOD is the model group; LXHY is the traditional Chinese medicine composition group; WXF is the literature prescription *, compared with the normal group, P < 0.05; #, compared with the model group Compared with the literature, P<0.05; △, compared with the literature, P<0.05

Figure 6 The effect of traditional Chinese medicine composition in treating immune vasculitis is better than that of any split prescription. NC is the normal group; MOD is the model group; LXHY is the traditional Chinese medicine composition; CF1 is split prescription 1; CF2 is split prescription 2; CF3 is split prescription CF4 is divided into square 4; CF5 is divided into square 5; CF6 is divided into square 6; CF7 is divided into square 7; CF8 is divided into square 8; CF9 is divided into square 9; CF10 is divided into square 10; CF11 is divided into square 11 ; CF12 is divided into squares 12; CF13 is divided into squares 13; CF14 is divided into squares 14. *, compared with the normal group, P<0.05;#, compared with the model group, P <0.05; △, compared with LXHY, P <0.05.

Detailed ways

The traditional Chinese medicinal materials used by the inventor in the process of preparing the pharmaceutical composition of the present invention have the following sources: Rehmannia glutinosa, the fresh or dried root tuber of the Scrophulariaceae plant Rehmannia glutinosa Libosch. Red peony root is the dried root of Paeonia lactiflora Pall. or Paeonia veitchii Lynch, a plant in the Ranunculaceae family. Mountain gardenia is the dried and mature fruit of gardenia jasminoides Ellis, a plant in the Rubiaceae family. Gypsum is a gypsum of the anhydrite family of sulfate minerals, mainly containing hydrated calcium sulfate CaSO ₄ ·2H ₂ O. Sedum sarmentosum, the whole plant of Sedum sarmentosum Bunge. White flower is the whole plant or root of Solanum lyratum Thunb, a plant of Solanaceae family; Hedyotis diffusa is the whole plant of Hedyotis diffusa Willd. [Oldenlandia diffusa (Willd.) Roxb. of Rubiaceae family. Buffalo horn is the horn of the bovine buffalo Bubalus bubalis Linnaeus. Forsythia suspensa (Thunb.) Vah is the dried fruit of the Oleaceae plant Forsythia suspensa (Thunb.) Vah. It is bitter and slightly cold in nature and returns to the lung, heart and small intestine meridians. Rhubarb is the dried root and rhizome of Rheum palmatum L., R. tanguticum Maxim.Ex Balf or R officinale Baill. of the Polygonaceae plant. Licorice is the dry root of the leguminous plant glycyrrhiza uralensis Fisch., glycyrrhiza inflata Bat. or glycyrrhiza glabra glycyrrhiza labra L. Antelope horn is the horn of Saiga tatarica Linnaeus, a bovine animal. It is salty and cold in nature and returns to the liver and heart meridians. Amber is a fossil-like substance formed by the long-term transformation of the resin of ancient Pinaceae plants, such as maples and pine trees, buried underground. Panax Notoginseng Powder is a powder made from the dried roots of Panax notoginseng (Burk.) FH Chen.

Based on many years of clinical practice experience, the inventor believes that the pathogenesis of immune vasculitis is composed of "evil-stasis-damage". In the acute stage, "evil" is the main factor, and the emphasis is on "eliminating evil", which mainly manifests as wind-heat, damp-heat, heat toxicity or blood-heat, so the treatment is "cooling blood"; in the remission stage, "evil" has been eliminated, and the emphasis is on "removing blood stasis", and in the recovery stage, "evil is eliminated and blood stasis is hidden", and the emphasis is on "tonifying deficiency", so the treatment is "co-operation". Furthermore, the Chinese medicine composition of the present invention contains a total of fourteen Chinese medicines. Among them, raw rehmannia, red peony root, gardenia, and gypsum clear away heat and cool blood, purge fire and remove dampness, and focus on eliminating "evil" as the main factor, while creeping vine, white peony root, oldenlandia diffusa, buffalo horn, forsythia, and antelope horn clear away heat and detoxify to strengthen the effect of "cooling blood" as the ministers; stir-fried rhubarb, amber powder, and Panax notoginseng powder work together to cool blood, promote blood circulation, remove blood stasis, The effect of dispersing blood stasis is the auxiliary, while licorice nourishes the spleen, lungs, and qi, and harmonizes the various medicines as the envoy, so as to achieve the effect of "cooperation". The combination of various medicines has the effects of cooling blood, removing dampness, dispersing blood stasis, and replenishing deficiency, so as to achieve the effect of "cooling blood and cooperating".

The antelope horn powder and Panax notoginseng powder in the traditional Chinese medicine composition of the present invention are both purchased from Shanghai Wanshicheng Traditional Chinese Medicine Products Co., Ltd.; the rest are granules prepared by China Resources Sanjiu Pharmaceutical Co., Ltd. The pharmaceutical composition of the present invention can be prepared according to conventional methods in this field, for example: S1. Grind antelope horn, amber, Panax notoginseng powder, etc. into fine powder and set aside; S2. Add 8 times the amount of the remaining eleven herbs such as Rehmannia glutinosa. Decoct with 6 times the amount of water twice, for 1 hour each time, filter, combine the filtrate, and concentrate into an extract with a relative density of 1.15 to 1.2 (80 to 85°C) for later use.

The traditional Chinese medicine composition of the present invention is easy to use, has definite curative effect, has few side effects, is low in cost, can be taken for a long time, and has good clinical efficacy in treating different types of immune vasculitis. In view of the high incidence of immune vasculitis and the huge physical and mental pain caused to patients, the current therapeutic effects of hormones, immunosuppressants, etc. are inconsistent, and there are limitations such as easy recurrence and large side effects. Therefore, the traditional Chinese medicine combination of the present invention The drug has good clinical application prospects.

The present invention will be further described below in conjunction with specific embodiments. It should be understood that these examples are only used to illustrate the invention and are not intended to limit the scope of the invention. Experimental methods without specifying specific conditions in the following examples usually follow conventional conditions or conditions recommended by the manufacturer. Unless otherwise stated, all percentages, ratios, proportions, or parts are by weight.

Unless otherwise defined, all technical and scientific terms used herein have the same meaning as familiar to one skilled in the art. In addition, any methods and materials similar or equivalent to those described can be used in the method of the present invention. The preferred implementation methods and materials described in this article are for demonstration purposes only.

The above-mentioned features mentioned in the present invention or the features mentioned in the embodiments may be combined in any combination. All features disclosed in this patent specification may be used in any combination, and each feature disclosed in the specification may be replaced by any alternative feature that serves the same, equivalent or similar purpose. Therefore, unless otherwise stated, the features disclosed are only general examples of equivalent or similar features.

Embodiment 1

Take 20g of Rehmannia glutinosa, 10g of red peony root, 20g of gardenia, 20g of raw gypsum, 20g of gypsophila, 20g of white flower, 20g of diffusa, 20g of buffalo horn, 10g of forsythia, 6g of fried rhubarb, 3g of licorice, and 0.6g of antelope horn. , amber powder 3g, notoginseng powder 2g.

The preparation method is as follows:

S1. Crush antelope horn, amber and Panax notoginseng into fine powder and set aside;

S2. Add 8 times and 6 times the amount of water to the remaining 11 herbs including Rehmannia glutinosa, respectively, and boil twice for 1 hour each time. Filter, combine the filtrate, and concentrate it into an extract with a relative density of 1.15-1.2 (80-85℃) for later use.

The administration method is as follows: mix the fine powder of S1 and the extract of S2, dissolve it in water and then administer it orally.

Embodiment 2

Take 25g of Rehmannia glutinosa, 13g of red peony root, 25g of gardenia, 25g of raw gypsum, 25g of gypsophila, 25g of white flower, 25g of diffusa, 25g of buffalo horn, 13g of forsythia, 9g of fried rhubarb, 6g of licorice, and 0.9g of antelope horn. , amber powder 4.5g, notoginseng powder 3g.

The preparation method and administration method are the same as in Example 1.

Embodiment 3

Take 30g of raw rehmannia, 15g of red peony root, 15g of gardenia, 30g of gypsum, 30g of creeping vine, 30g of white peony root, 30g of oldenlandia diffusa, 30g of buffalo horn, 15g of forsythia, 12g of stir-fried rhubarb, 9g of licorice, 1.2g of antelope horn, 6g of amber powder, and 4g of Panax notoginseng powder.

The preparation method and administration method are the same as in Example 1.

Embodiment 4

Take 35g of Rehmannia glutinosa, 17g of red peony root, 35g of gardenia, 45g of raw gypsum, 35g of gypsophila, 35g of white flower, 35g of diffusa, 45g of buffalo horn, 17g of forsythia, 12g of fried rhubarb, 12g of licorice, and 1.8g of antelope horn. , amber powder 9g, notoginseng powder 6g.

The preparation method and administration method are the same as in Example 1.

Embodiment 5

Take 40g of Rehmannia glutinosa, 20g of red peony root, 40g of gardenia, 60g of raw gypsum, 40g of gypsophila, 40g of white flower, 40g of diffusa, 40g of buffalo horn, 20g of forsythia, 20g of fried rhubarb, 15g of licorice, and 2.4g of antelope horn. , amber powder 12g, notoginseng powder 8g.

The preparation method and administration method are the same as in Example 1.

Example 6 Animal Experiment on Treatment of Immune Vasculitis with Traditional Chinese Medicine Composition

Experimental animal: Wistar rat

Experimental drugs: Traditional Chinese medicine compositions were prepared according to Example 3

Experimental method: 4-week-old male Wistar rats were used as model animals. After adaptive feeding for one week, they were randomly divided into normal group, model group and medication group. The model group and the medication group were injected with sodium laurate through the femoral artery to create an immune vasculitis model. The medication group was given Chinese medicine composition intervention within 2 hours after modeling, while the model group and the normal group were given equal volumes of drinking water. The dose administered to rats is 6.1 times the human dose. 200ul was administered intragastrically every day for a total of 14 days of intervention. The next day, the experimental rats in each group were processed, photos were taken, and the blood flow of the lower limbs was detected using a super-resolution point scanning laser Doppler blood flow imager to evaluate the therapeutic effect of the traditional Chinese medicine composition on immune vasculitis. Their hearts and livers were also taken. , kidney, fixed in 4% paraformaldehyde, and stained with H&E to evaluate the safety of Liangxue and Yingfang.

Statistical method: SPSS21.0 for windows statistical software was used for statistical analysis. Blood flow is measurement data. One-way classification ANOVA using one-way analysis of variance (one-way-classification ANOVA) is used, and t-test is used for pairwise comparison. P<0.05 was used as the criterion for statistical difference.

Experimental results: As shown in Figure 1, compared with the normal group, the toes and soles of the lower limbs of the rats in the model group all fell off, the stumps of the feet turned black, and the pads were red and swollen; the Chinese medicine composition significantly improved the degree of necrosis of the rats' lower limbs, only the ends of the feet turned black, and the swelling of the pads was significantly reduced. It can be seen that the Chinese medicine composition can significantly improve the degree of necrosis of the rats' lower limbs. As shown in Figures 2a and 2b, the ultra-high resolution point scanning laser Doppler blood flow imager detected that compared with the normal group, the blood flow of the lower limbs of the rats in the model group was significantly reduced; compared with the model group, the Chinese medicine composition can significantly increase the blood flow of the lower limbs of the rats, with statistical differences (P < 0.05). As shown in Figure 3, after treatment with the Chinese medicine composition, there were no obvious abnormalities in the heart, brain, and kidneys of the rats, which shows that the Chinese medicine composition has no obvious toxic and side effects.

Example 7 Comparative study of traditional Chinese medicine compositions and literature prescriptions

Experimental animals: Japanese big-eared young rabbits

Experimental drugs: Traditional Chinese medicine compositions were prepared according to Example 3

Literature recipe: 30 pieces of buffalo horn slices (fried first), 15g raw rehmannia, 15g paeonol bark, 50g gypsum (fried first), 20g lithospermum, 20g fenugreek, 30g diffusa, 5g Zhijun, 30g Scutellaria barbata, 30g of Tengli root, 20g of Chuipencao, 15g of Liuyi powder (decoction), according to the literature (Zhang Dongping, Cao Jianchun. Treating cutaneous vasculitis from the perspective of "evil" - Xi Jiuyi's experience in treating cutaneous vasculitis [J] . Chinese Journal of Integrated Traditional Chinese and Western Medicine Surgery, 2004, 06: 51-52.) Prepared by the disclosed method.

Experimental method: 4-week-old Japanese big-eared juvenile rabbits were used as model animals. After adaptive breeding for one week, they were randomly divided into a normal group, a model group, a traditional Chinese medicine composition group, and a literature prescription group. The experimental rabbits in the model group, Chinese medicine composition group, and literature prescription group were all slowly injected intravenously with 10% bovine serum albumin 25 ml/Kg, and the normal group was given an equal dose of normal saline. Two weeks later, bovine serum albumin was injected again according to the above method to induce immune vasculitis. After the first modeling, the Chinese medicine composition and literature prescription intervention were given on the next day, and the model group and the normal group were given equal volumes of drinking water. The dose administered to rabbits is 2.3 times the human dose. The intervention was conducted for a total of 14 days, and the coronary arteries were isolated for H&E staining and elastic fiber staining on the next day to evaluate the therapeutic effect of traditional Chinese medicine compositions and literature prescriptions on immune vasculitis.

Statistical methods: SPSS 21.0 for windows statistical software was used for statistical analysis. Kruskal-Wallis H test was used for rank data with completely randomized design and multiple sample comparisons, and Wilcoxon rank sum test was used for pairwise comparisons. P < 0.05 was used as the criterion for statistically significant differences.

Experimental results: Scores were scored based on the degree of inflammatory cell infiltration, necrosis, and shedding in the arterial tissue, as well as the arrangement and integrity of elastic fibers, and were marked -,±,+,++,+++,++++, among which, - It means there is no obvious damage; ++++ means there is extremely severe damage. As shown in Figures 4 and 5, compared with the model group, the traditional Chinese medicine composition and literature prescriptions significantly reduced the infiltration of inflammatory cells and significantly improved the lesions of elastic fibers, with statistical differences (P<0.05). However, the therapeutic effect of the traditional Chinese medicine composition was significantly better than that of the literature prescription, and there was a statistical difference (P<0.05).

Example 8 Comparative study of traditional Chinese medicine compositions and split prescriptions

Experimental animals: Balb/c mice

Experimental drugs: Traditional Chinese medicine compositions were prepared according to Example 3

Recipe 1: Drug composition: 15g red peony root, 15g gardenia, 30g gypsum, 30g gypsum, 30g white flower, 30g diffusa, 30g buffalo horn, 15g forsythia, 12g fried rhubarb, 9g licorice, antelope horn 1.2g, amber powder 6g, notoginseng powder 4g.

Recipe 2 contains ingredients: 30g of raw rehmannia, 15g of gardenia, 30g of gypsum, 30g of gypsum, 30g of white flower, 30g of diffusa, 30g of buffalo horn, 15g of forsythia, 12g of fried rhubarb, 9g of licorice, and 1.2 antelope horn. g, 6g amber powder, 4g notoginseng powder.

Recipe 3 consists of: 30g raw rehmannia, 15g red peony root, 30g gypsum, 30g pendant grass, 30g white bark, 30g diffusa, 30g buffalo horn, 15g forsythia, 12g fried rhubarb, 9g licorice, 1.2g antelope horn. , amber powder 6g, notoginseng powder 4g.

Recipe 4 consists of: 30g raw rehmannia root, 15g red peony root, 15g mountain gardenia, 30g pendant grass, 30g white flowering herb, 30g diffusa, 30g buffalo horn, 15g forsythia, 12g fried rhubarb, 9g licorice, antelope horn 1.2g, amber powder 6g, notoginseng powder 4g.

The composition of Recipe 5: 30g of Rehmannia glutinosa, 15g of red peony root, 15g of gardenia, 30g of gypsum, 30g of gypsum, 30g of diffusa, 30g of buffalo horn, 15g of forsythia, 12g of fried rhubarb, 9g of licorice, and 1.2g of antelope horn. , amber powder 6g, notoginseng powder 4g.

Recipe 6: Drug composition: 30g of Rehmannia glutinosa, 15g of red peony root, 15g of gardenia, 30g of raw gypsum, 30g of gypsum, 30g of Hedyotis diffusa, 30g of buffalo horn, 15g of forsythia, 12g of fried rhubarb, 9g of licorice, and 1.2 antelope horn. g, 6g amber powder, 4g notoginseng powder.

The composition of Recipe 7: 30g of raw rehmannia, 15g of red peony root, 15g of gardenia, 30g of raw gypsum, 30g of gypsum, 30g of white thorn, 30g of buffalo horn, 15g of forsythia, 12g of fried rhubarb, 9g of licorice, 1.2g of antelope horn, Amber powder 6g, Panax notoginseng powder 4g.

Recipe 8: Drug composition: 30g of Rehmannia glutinosa, 15g of red peony root, 15g of gardenia, 30g of raw gypsum, 30g of gypsum, 30g of white bark, 30g of diffusa, 15g of forsythia, 12g of fried rhubarb, 9g of licorice, 1.2 antelope horn g, 6g amber powder, 4g notoginseng powder.

Recipe 9 consists of: 30g raw rehmannia, 15g red peony root, 15g mountain gardenia, 30g raw gypsum, 30g pendant grass, 30g white flower, 30g diffusa, 30g buffalo horn, 12g fried rhubarb, 9g licorice, 1.2 antelope horn g. Amber powder 6g, Panax notoginseng powder 4g.

The composition of the 10 ingredients in the recipe: 30g of Rehmannia glutinosa, 15g of red peony root, 15g of gardenia, 30g of raw gypsum, 30g of gypsum, 30g of white flower, 30g of diffusa, 30g of buffalo horn, 15g of forsythia, 9g of licorice, and 1.2 antelope horn. g, 6g amber powder, 4g notoginseng powder.

Recipe 11: Drug composition: 30g of Rehmannia glutinosa, 15g of red peony root, 15g of gardenia, 30g of raw gypsum, 30g of gypsum, 30g of alba, 30g of diffusa, 30g of buffalo horn, 15g of forsythia, 12g of fried rhubarb, antelope horn 1.2g, amber powder 6g, notoginseng powder 4g.

The composition of the 12 ingredients in the recipe: 30g of Rehmannia glutinosa, 15g of red peony root, 15g of gardenia, 30g of raw gypsum, 30g of gypsum, 30g of alba, 30g of diffusa, 30g of buffalo horn, 15g of forsythia, 12g of fried rhubarb, and 9g of licorice. , amber powder 6g, notoginseng powder 4g.

Recipe 13 contains ingredients: 30g of Rehmannia glutinosa, 15g of red peony root, 15g of gardenia, 30g of raw gypsum, 30g of gypsum, 30g of alba, 30g of diffusa, 30g of buffalo horn, 15g of forsythia, 12g of fried rhubarb, and 9g of licorice. , antelope horn 1.2g, Panax notoginseng powder 4g.

Recipe 14 contains ingredients: 30g of Rehmannia glutinosa, 15g of red peony root, 15g of gardenia, 30g of raw gypsum, 30g of gypsum, 30g of alba, 30g of diffusa, 30g of buffalo horn, 15g of forsythia, 12g of fried rhubarb, and 9g of licorice. , antelope horn 1.2g, amber powder 6g.

Preparation method of the split medicine: prepared according to the method of Example 1.

Experimental method: 4-week-old, female, Balb/c mice were used as model animals. After adaptive breeding for one week, they were randomly divided into blank group, model group, Chinese medicine composition group, and each split recipe group (split recipe 1, split recipe 2. Split side 3, split side 4, split side 5, split side 6, split side 7, split side 8, split side 9, split side 10, split side 11, split side 12, split side 13, split side 14) . The mice in the model group, the traditional Chinese medicine composition group, and each split prescription group were injected with 0.5 ml of Lactobacillus casei cell wall component at 1 m part/ml through the tail vein to create an immune vasculitis mouse model. The normal group was injected with an equal volume of Lactobacillus casei through the tail vein. PBS. The Chinese medicine composition and each divided prescription intervention were given on the next day after the self-modeling. The model group and the normal group were given equal volumes of drinking water. The dose administered to mice was 9.3 times the human dose. Give 200ul by gavage every day. After 7 days of intervention, the animals in each group were treated the next day, and the H&E staining of the tail vein was detected to evaluate the therapeutic effect of the traditional Chinese medicine composition and the various prescriptions on immune vasculitis.

Statistical method: SPSS21.0 for windows statistical software was used for statistical analysis. The hierarchical data used the Kruskal-Wallis H test for multiple sample comparisons with a completely random design, and the Wilcoxon rank sum test was used for pairwise comparisons. P<0.05 was used as the criterion for statistical difference.

Experimental results: Score according to the degree of inflammatory cell infiltration, necrosis, thrombosis, etc. in the tail vein, marked -,±,+,++,+++,++++ respectively, where - represents no obvious damage; ++ ++ indicates extremely severe damage. As shown in Figure 6, compared with the model group, the traditional Chinese medicine composition and each disassembled prescription significantly reduced the infiltration of inflammatory cells in the tail vein, with statistical differences (P<0.05). However, the therapeutic effect of any split recipe with less than one ingredient is inferior to that of the traditional Chinese medicine composition, and there is a statistical difference (P<0.05).

Example 9 Clinical Comparative Study of Traditional Chinese Medicine Compositions and Hormones

1.Clinical data and methods

1.1 Research objects

All patients with immune vasculitis who visited the outpatient and inpatient departments of the Vascular Department of Shanghai Hospital of Integrated Traditional Chinese and Western Medicine.

1.2 Diagnostic criteria

1.2.1 Western medicine diagnostic criteria

Diagnosis was made with reference to the 1990 ACR classification criteria and the 2012 Chapel-Hill Consensus Conference classification criteria.

1.2.2 Diagnostic criteria of TCM syndrome types:

According to the "Diagnostic and Efficacy Standards for Diseases of Traditional Chinese Medicine", it is consistent with the damp-heat stasis type.

1.2.3 Inclusion criteria:

① Meet the diagnostic criteria for immune vasculitis; ② Meet the damp-heat stasis syndrome; ③ No age limit; ④ Both men and women are welcome; ⑤ Voluntarily join the clinical trial study and sign an informed consent form.

1.2.4 Exclusion criteria:

① Those combined with severe liver and kidney dysfunction, systemic infectious diseases, malignant tumors and mental illness; ② Severe allergic constitution; ③ Pregnant or lactating women; ④ Those allergic to the test drug or its components.

1.2.5 Estimation of sample size

Refer to the relevant formula calculations in the 6th edition of "Medical Statistics". From the perspective of effectiveness, according to statistical requirements, a superiority test and a two-sided test were used, α = 0.05, β = 0.2, the expected average effective rate was 0.90, and the estimated number of cases was 126. Taking into account the dropout factor, the decision was made The trial was conducted on 152 cases, with traditional Chinese medicine and Western medicine components There are 76 cases.

1.2.6 Ethical review

This study has been reviewed by the Ethics Committee of Shanghai Hospital of Integrated Traditional Chinese and Western Medicine and received an ethics number

ChiCTR2100052797.

1.3 Drug treatment

Western medicine group: Maintenance treatment with methylprednisolone tablets, 4 to 8 mg/d. Traditional Chinese medicine group: The traditional Chinese medicine composition of the present invention is given on the basis of maintenance treatment with methylprednisolone tablets at 4 to 8 mg/d.

The traditional Chinese medicine composition is prepared according to the dosage in Example 3. Among them, antelope horn powder and Panax notoginseng powder were purchased from Shanghai Wanshicheng Traditional Chinese Medicine Products Co., Ltd. Shengdi and other granules were purchased from Jiangyin Tianjiang Pharmaceutical Co., Ltd. Mix all the granules, antelope horn powder, and Panax notoginseng powder, mix with boiling water, and take it orally in two doses.

Both groups were treated for 12 weeks and followed up for half a year.

1.4 Observation indicators

The Birmingham Systemic Vasculitis Activity Score (BVAS) was performed on patients in each group before and after treatment, and the patients were followed up to observe Cushing's syndrome-like symptoms such as central obesity, moon face, and increased hair growth.

The efficacy evaluation is based on the efficacy index, which is (total points before treatment - total points after treatment) ÷ total points before treatment. ① Markedly effective: symptoms are significantly improved, and syndrome points are reduced by ≥ 70% compared with before treatment; ② Effective: symptoms are improved, and syndrome points are reduced by ≥ 30% and < 70% compared with before treatment; ③ Ineffective: symptoms are not improved, and syndrome points are reduced by ≥ 30% compared with before treatment The score is reduced by <30% compared with before treatment; ④Aggravation: the symptoms worsen, and the syndrome score is reduced by <0% compared with before.

Statistical methods: SPSS21.0 for windows statistical software was used for statistical analysis. Count data were expressed by rates and composition ratios, and ^x2 test was used. P<0.05 was used as the criterion for statistical difference.

2. Results

As shown in Table 1, a total of 152 cases of immune vasculitis were collected, 76 cases each in the traditional Chinese medicine group and the western medicine group. Among them, the total effective rate of the traditional Chinese medicine group was 97.34%. Compared with the western medicine group, the effective rate was significantly improved and statistically significant. Difference (P<0.05); and through follow-up, it was found that 13 patients in the Western medicine group developed Cushing's syndrome to varying degrees after taking methylprednisolone tablets, while no cases of Cushing's syndrome were found in the traditional Chinese medicine group. It can be seen that the combination of traditional Chinese medicine composition and western medicine has a significant effect in the treatment of immune vasculitis, and the traditional Chinese medicine composition can also significantly prevent Cushing's syndrome caused by hormone (methylprednisolone tablets) treatment.

Table 1 Comparison of clinical efficacy between two groups/case

Example 10 Clinical research on the treatment of various immune vasculitis diseases with traditional Chinese medicine compositions

Experimental method: The inventor collected 95 cases of immune vasculitis, including 30 cases of nodular vasculitis, 10 cases of Takayasu arteritis, 10 cases of thromboangiitis obliterans, 15 cases of rheumatoid vasculitis, and systemic erythema Ten cases of lupus vasculitis, 10 cases of scleroderma vasculitis, and 10 cases of ACNA-related vasculitis were treated with a traditional Chinese medicine composition (same as Example 9) for 14 days, and the Birmingham Systemic Vasculitis Activity Score (BVAS) was filled in before and after treatment. ) to evaluate the therapeutic effect of traditional Chinese medicine compositions. As shown in Table 2, the traditional Chinese medicine compositions significantly improved symptoms such as redness, swelling, heat and pain in various patients.

Table 2 Observation on the clinical efficacy of traditional Chinese medicine compositions in treating various immune vasculitis diseases

Various aspects of the present invention have been described above. However, it should be understood that equivalent changes and modifications can be made by those skilled in the art without departing from the spirit of the present invention, and such changes and modifications also fall within the scope of the appended claims of the present application.

Claims (10)

1. A traditional Chinese medicine composition for treating immune vasculitis, which is characterized in that it is made from the following raw materials by weight: 15 to 40 parts of raw rehmannia root, 10 to 20 parts of red peony root, 10 to 40 parts of mountain gardenia, and 15 to 15 parts of gypsum. 60 parts, 15 to 40 parts of Trichosanthes chinensis, 15 to 40 parts of Amaranthus alba, 15 to 40 parts of Hedyotis diffusa, 15 to 40 parts of buffalo horn, 10 to 20 parts of Forsythia suspensa, 6 to 20 parts of fried rhubarb, 3 licorice ~15 parts, antelope horn 0.6~2.4 parts, amber powder 3~12 parts, Panax notoginseng powder 2~8 parts.
2. The Chinese medicine composition according to claim 1, characterized in that the Chinese medicine composition is made of the following raw materials by weight: 30 parts of raw rehmannia root, 15 parts of red peony root, 15 parts of gardenia, 30 parts of gypsum, 30 parts of potwort, 30 parts of white flower, 30 parts of Hedyotis diffusa, 30 parts of buffalo horn, 15 parts of forsythia, 12 parts of fried rhubarb, 9 parts of licorice, 1.2 parts of antelope horn, 6 parts of amber powder, notoginseng powder 4 parts.
3. The Chinese medicine composition according to claim 1, characterized in that the Chinese medicine composition is made of the following raw materials by weight: 20 parts of raw rehmannia root, 10 parts of red peony root, 20 parts of gardenia, 20 parts of gypsum, 20 parts of potwort, 20 parts of white flower, 20 parts of Hedyotis diffusa, 20 parts of buffalo horn, 10 parts of forsythia, 6 parts of fried rhubarb, 3 parts of licorice, 0.6 parts of antelope horn, 3 parts of amber powder, notoginseng powder 2 servings.
4. The Chinese medicine composition according to claim 1, characterized in that the Chinese medicine composition is made of the following raw materials by weight: 25 parts of raw rehmannia root, 13 parts of red peony root, 25 parts of gardenia, 25 parts of gypsum, 25 parts of potgrass, 25 parts of white flower, 25 parts of Hedyotis diffusa, 25 parts of buffalo horn, 13 parts of forsythia, 9 parts of fried rhubarb, 6 parts of licorice, 0.9 parts of antelope horn, 4.5 parts of amber powder, notoginseng powder 3 copies.
5. The traditional Chinese medicine composition according to claim 1, characterized in that the traditional Chinese medicine composition is made of the following raw materials by weight: 35 parts of raw rehmannia root, 17 parts of red peony root, 35 parts of mountain gardenia, 45 parts of gypsum, 35 parts of potwort, 35 parts of white flower, 35 parts of Hedyotis diffusa, 45 parts of buffalo horn, 17 parts of forsythia, 12 parts of fried rhubarb, 12 parts of licorice, 1.8 parts of antelope horn, 9 parts of amber powder, notoginseng powder Serves 6.
6. The traditional Chinese medicine composition according to claim 1, characterized in that the traditional Chinese medicine composition is made of the following raw materials by weight: 40 parts of raw rehmannia root, 20 parts of red peony root, 40 parts of mountain gardenia, 60 parts of gypsum, 40 parts of potwort, 40 parts of white flower, 40 parts of Hedyotis diffusa, 40 parts of buffalo horn, 20 parts of forsythia, 20 parts of fried rhubarb, 15 parts of licorice, 2.4 parts of antelope horn, 12 parts of amber powder, notoginseng powder Serves 8.
7. A traditional Chinese medicine compound preparation for the treatment of immune vasculitis, characterized in that the traditional Chinese medicine compound preparation is a decoction with the traditional Chinese medicine composition described in claim 1 or 2 or 3 or 4 or 5 or 6 as an active ingredient. Granules, powders, capsules, tablets or oral liquids.
8. The traditional Chinese medicine compound preparation according to claim 7, characterized in that the traditional Chinese medicine compound preparation is a decoction.
9. The application of the traditional Chinese medicine composition as claimed in claim 1 or 2 or 3 or 4 or 5 or 6 in the preparation of a medicine for the treatment of immune vasculitis diseases, the immune vasculitis diseases being selected from the group consisting of nodular vasculitis , Takayasu arteritis, thromboangiitis obliterans, rheumatoid vasculitis, systemic lupus erythematosus vasculitis, scleroderma vasculitis or ACNA-associated vasculitis.
10. The application of the traditional Chinese medicine compound preparation according to claim 7 or 8 in the preparation of medicine for the treatment of immune vasculitis diseases, the immune vasculitis diseases being selected from the group consisting of nodular vasculitis, Takayasu arteritis, and thrombotic vasculitis obliterans. Vasculitis, rheumatoid vasculitis, systemic lupus erythematosus vasculitis, scleroderma vasculitis, or ACNA-associated vasculitis.