阅读说明：本技术 一种治疗过敏性紫癜的中药制剂及制备方法与应用 (Traditional Chinese medicine preparation for treating anaphylactoid purpura as well as preparation method and application thereof ) 是由 倪鑫 王晓玲 杨燕 张艳菊 张萌 胡艳 于飞 宋更申 郑红兵 郜金军 于 2020-05-19 设计创作，主要内容包括：本发明提供一种治疗过敏性紫癜的中药制剂及制备方法与应用。中药组合物包括以下重量份计的原料：青黛3份,紫草5～10份,绵马贯众6～12份,丹参6～12份,白芷3～9份,北寒水石6～12份,威灵仙6～12份,茵陈6～12份。中药制剂由该中药组合物制成。本发明提供的中药组合物可以在保证原处方的药用疗效的同时进一步降低胃肠道不良反应。(The invention provides a traditional Chinese medicine preparation for treating anaphylactoid purpura, a preparation method and application thereof. The traditional Chinese medicine composition comprises the following raw materials in parts by weight: 3 parts of indigo naturalis, 5-10 parts of lithospermum, 6-12 parts of rhizoma dryopteris crassirhizomae, 6-12 parts of salvia miltiorrhiza, 3-9 parts of angelica dahurica, 6-12 parts of northern gypsum rubrum, 6-12 parts of radix clematidis and 6-12 parts of oriental wormwood. The Chinese medicinal preparation is prepared from the Chinese medicinal composition. The traditional Chinese medicine composition provided by the invention can further reduce adverse reactions of gastrointestinal tracts while ensuring the medicinal curative effect of the original prescription.)

1. A traditional Chinese medicine composition for treating anaphylactoid purpura is characterized by comprising the following raw materials in parts by weight: 3 parts of indigo naturalis, 5-10 parts of lithospermum, 6-12 parts of rhizoma dryopteris crassirhizomae, 6-12 parts of salvia miltiorrhiza, 3-9 parts of angelica dahurica, 6-12 parts of northern gypsum rubrum, 6-12 parts of radix clematidis and 6-12 parts of oriental wormwood.

2. The traditional Chinese medicine composition for treating allergic purpura according to claim 1, which comprises the following raw materials in parts by weight: 3 parts of indigo naturalis, 6-9 parts of lithospermum, 8-10 parts of rhizoma dryopteris crassirhizomae, 8-10 parts of salvia miltiorrhiza, 7-8 parts of angelica dahurica, 8-10 parts of northern gypsum rubrum, 8-10 parts of radix clematidis and 8-10 parts of oriental wormwood;

specifically, the traditional Chinese medicine composition for treating anaphylactoid purpura comprises the following raw materials in parts by weight: 3 parts of indigo naturalis, 9 parts of lithospermum, 9 parts of rhizoma dryopteris crassirhizomae, 9 parts of salvia miltiorrhiza, 6 parts of angelica dahurica, 9 parts of north gypsum rubrum, 9 parts of radix clematidis and 9 parts of oriental wormwood.

3. A Chinese medicinal preparation for treating allergic purpura, which is characterized in that the Chinese medicinal preparation is prepared by taking the Chinese medicinal composition of claim 1 or 2 as a main active ingredient or a single active ingredient, or further comprises pharmaceutically usable auxiliary materials.

4. The traditional Chinese medicine preparation for treating allergic purpura according to claim 3, which is a granule, a tablet (containing dispersible tablets and effervescent tablets), a pill (containing drop pills), a capsule, an oral liquid, a syrup or an external preparation;

wherein, when the traditional Chinese medicine preparation is granules, preferably used auxiliary materials comprise sucrose and dextrin; wherein the content of the first and second substances,

preferably, the weight ratio of the sucrose to the dextrin is 2-4: 2, and more preferably 3: 2; and/or the presence of a gas in the gas,

preferably, the weight sum of the sucrose and the dextrin is 0.15-0.30 time of the weight sum of the raw medicinal materials, and more preferably 0.20-0.25 time of the weight sum of the raw medicinal materials.

5. The method for preparing a Chinese medicinal preparation for treating allergic purpura according to claim 3 or 4, which comprises: taking the medicinal materials according to the proportion; firstly, water is added into northern glauberite for decoction; adding indigo naturalis, radix Arnebiae, rhizoma Dryopteris Crassirhizomatis, Saviae Miltiorrhizae radix, radix Angelicae Dahuricae, radix Clematidis, and herba Artemisiae Scopariae into the first decoction, and decocting with water; obtaining a second decoction.

6. The method for preparing a Chinese medicinal preparation for treating allergic purpura according to claim 3 or 4, comprising the following steps:

1) taking the northern glauber's salt according to the proportion, adding 10-50 times of water by weight for immersing, and decocting for 10-60 min to obtain a decoction;

2) adding indigo naturalis, lithospermum, rhizoma dryopteris crassirhizomae, salvia miltiorrhiza, angelica dahurica, radix clematidis and oriental wormwood into the decoction obtained in the step 1) according to the proportion, adding water with the weight being 8-15 times that of the medicinal materials, decocting for 1-4 times, decocting for 1-3 hours each time, filtering, and concentrating the filtrate to obtain an extract with the relative density of 1.10-1.25 (60 ℃); or further comprising:

3) spraying the extract obtained in the step 2) with a proper amount of saccharin sodium, sucrose and dextrin, and preparing into granules.

7. The preparation method according to claim 6, wherein in step 1), the decoction is carried out for 15 min; and/or the presence of a gas in the gas,

in the step 2), adding water for decocting for 2 times, and adding 12 times and 8 times of water by weight respectively for 1 hour each time; and/or the presence of a gas in the gas,

specifically, in the step 2), the filtrate is concentrated to a relative density of 1.10 to 1.15(60 ℃).

8. The method according to claim 6 or 7, wherein in step 3), the weight ratio of sucrose to dextrin is 2-4: 2, preferably 3:2, and/or,

the weight sum of the added cane sugar and the added dextrin is 0.15-0.30 time, preferably 0.20-0.25 time of the weight sum of the raw medicinal materials.

9. A Chinese medicinal preparation for treating allergic purpura, which is prepared by the method of any one of claims 5 to 8.

10. Use of the Chinese medicinal composition of claim 1 or 2 or the Chinese medicinal preparation of any one of claims 3, 4 and 9 in the preparation of a medicament for treating allergic purpura.

Technical Field

The invention relates to a Chinese medicinal composition for treating allergic purpura; the invention also provides a traditional Chinese medicine preparation prepared from the traditional Chinese medicine composition, a preparation method and application.

Background

Allergic purpura (HSP) is an immune complex-mediated allergic vasculitis which invades the skin and other organs, namely, the tiny arteries and capillaries, and is mainly manifested by purpura, abdominal pain, joint gall, hematuria, proteinuria and the like, but platelets are not reduced. Most of the cases take skin purpura as the first symptom, about 2/3 cases show digestive tract symptoms, about 20-80% of HSP affect the kidney, most of the cases show macroscopic hematuria or microscopic hematuria and proteinuria 2-4 weeks after the purpura, and the kidney damage is also called allergic purpura.

Allergic purpura belongs to the category of 'blood disease' in traditional Chinese medicine, and the key mechanism of the disease is wind, heat, deficiency and blood stasis, which are usually caused in children or adolescence, and patients suffer from congenital yin deficiency and dryness, are repeatedly affected by heat pathogen entering collaterals, qi and yin are damaged, and collaterals block blood stasis.

Western medicine thinks that allergic purpura is caused by humoral immunity abnormity, release of cell factors and inflammatory mediators and participation of a blood coagulation mechanism, multiple studies show that IgA1 antibodies and IgA circulating immune complexes can be detected in HSP patients, the patients have hyperviscosity blood, and meanwhile, many HSP patients are discovered to have diseases in children or adolescence due to the fact that the HSP patients do not have idiosyncratic physique, and the findings are similar to the causes of congenital yin deficiency and dryness, repeated heat pathogen invasion into collaterals, qi and yin consumption injury, and collateral obstruction and blood stasis of the HSP patients considered by traditional Chinese medicine.

The treatment of the disease is usually applied to the treatment of antiallergic drugs, drugs for reducing vascular permeability, platelet aggregation inhibitors, adrenocortical hormone, immunosuppressants and the like besides eliminating the cause of the disease clinically, but has the following defects: the traditional Chinese medicine composition has poor curative effect, is easy to cause purpuric nephritis, and can cause rebound or aggravation of disease due to the influence of factors such as physique and environmental change in the process of applying hormone therapy.

The hospital preparation-Qing Zi mixture (Huang Jing, Yan, Qing Zi mixture for treating allergic purpura in children and mechanism discussion, Chinese materia medica, 2014,32(7):1789 and 1792.) has better treatment effect on the disease. The medicine composition of the Qing Zi mixture comprises 3g of indigo naturalis, 15g of lithospermum, 6g of angelica dahurica, 10g of salvia miltiorrhiza, 15g of oriental wormwood, 15g of rhizoma dryopteris crassirhizomae, 10g of radix clematidis and 15g of north gypsum rubrum. The natural indigo and the lithospermum are monarch drugs, and the lithospermum has bitter and cold smell and purple color entering blood, so heat in blood is cleared up. In ancient times, the heat accumulation of zang-fu organs is treated, and later men are specialized in treating pox and ulcer, and rash is the main purpose of cooling blood and clearing heat. The gromwell has the functions of resisting pathogenic microorganisms and resisting inflammation through pharmacological research. Qing Dai clears away heat and toxic material, cools blood and removes ecchymoses. Can be used for treating warm toxic macula, hematemesis and epistaxis. The angelica dahurica and the salvia miltiorrhiza are used as ministerial medicines, and the angelica dahurica has the effects of relieving exterior syndrome, dispelling wind, dredging orifices, relieving pain, reducing swelling and expelling pus, and is used for treating pyocutaneous disease, pyogenic infection and skin rheumatism and pruritus. Dan Shen can activate blood, cool blood and resolve abscess, so it is indicated for sores, ulcers, abscess and swollen abscess. The two drugs further enhance the functions of clearing heat and removing toxicity, cooling blood and removing stasis, so the traditional Chinese medicine is a ministerial drug. Although the prescription has a good treatment effect on allergic purpura, in clinical use, the phenomena of loose stool and aggravation of gastrointestinal adverse symptoms are found to occur after the prescription is taken by patients with weakness of the spleen and the stomach, the adverse reactions tend to aggravate year by year in children, and other adverse reactions occasionally have adverse events of proteinuria or hematuria, so that the prescription is limited to be used in children patients.

Disclosure of Invention

The inventor surprisingly finds that under the condition of ensuring that the composition of the medicinal materials in the original prescription is not changed, the dosage of the monarch drug lithospermum is reduced to be two thirds or less of the dosage of the original prescription, and the dosages of other medicinal materials are respectively reduced, so that the adverse reaction of the gastrointestinal tract can be further reduced while the medicinal curative effect of the original prescription is ensured. Based on the discovery, the invention firstly provides a traditional Chinese medicine composition for treating anaphylactoid purpura, which has a positive curative effect, less side effects and lower cost for treating anaphylactoid purpura.

A traditional Chinese medicine composition for treating anaphylactoid purpura comprises the following raw materials in parts by weight: 3 parts of indigo naturalis, 5-10 parts of lithospermum, 6-12 parts of rhizoma dryopteris crassirhizomae, 6-12 parts of salvia miltiorrhiza, 3-9 parts of angelica dahurica, 6-12 parts of northern gypsum rubrum, 6-12 parts of radix clematidis and 6-12 parts of oriental wormwood. Because the dosage of the monarch drug, the lithospermum, the ministerial drugs, the adjuvant drugs and the conductant drugs is reduced, the adverse reaction of the gastrointestinal tract is obviously reduced, and the drug effect of the original prescription can be ensured.

In some embodiments, the traditional Chinese medicine composition for treating allergic purpura comprises the following raw materials in parts by weight: 3 parts of indigo naturalis, 6-9 parts of lithospermum, 8-10 parts of rhizoma dryopteris crassirhizomae, 8-10 parts of salvia miltiorrhiza, 7-8 parts of angelica dahurica, 8-10 parts of northern gypsum rubrum, 8-10 parts of radix clematidis and 8-10 parts of oriental wormwood.

In some preferred embodiments, the traditional Chinese medicine composition for treating allergic purpura comprises the following raw materials in parts by weight: 3 parts of indigo naturalis, 9 parts of lithospermum, 9 parts of rhizoma dryopteris crassirhizomae, 9 parts of salvia miltiorrhiza, 6 parts of angelica dahurica, 9 parts of north gypsum rubrum, 9 parts of radix clematidis and 9 parts of oriental wormwood.

In some embodiments of the present invention, the traditional Chinese medicine composition for treating allergic purpura is prepared from or prepared from natural indigo, lithospermum, rhizoma dryopteris crassirhizomae, salvia miltiorrhiza, angelica dahurica, north gypsum rubrum, clematis root and oriental wormwood according to the weight ratio. The invention also provides a preparation method of the traditional Chinese medicine composition for treating anaphylactoid purpura, for example, the traditional Chinese medicine composition can be prepared by mixing the medicinal materials according to the conventional method in the field. In some embodiments, the medicinal materials are pulverized and mixed.

The invention also provides a traditional Chinese medicine preparation for treating anaphylactoid purpura, which is prepared by taking the traditional Chinese medicine composition for treating anaphylactoid purpura as a main active ingredient, or further comprises pharmaceutically available auxiliary materials.

In some embodiments of the present invention, the traditional Chinese medicine preparation for treating allergic purpura is prepared by using the traditional Chinese medicine composition for treating allergic purpura as a sole active ingredient, or further comprises pharmaceutically acceptable auxiliary materials.

In some embodiments of the present invention, the traditional Chinese medicine preparation for treating allergic purpura is prepared by taking the traditional Chinese medicine composition for treating allergic purpura as a main active ingredient or only using the traditional Chinese medicine composition for treating allergic purpura as an independent active ingredient (that is, does not contain pharmaceutically acceptable auxiliary materials), or is prepared by taking the traditional Chinese medicine composition as a main active ingredient or only using the traditional Chinese medicine composition and using the pharmaceutically acceptable auxiliary materials.

The traditional Chinese medicine preparation for treating anaphylactoid purpura can be prepared into various common dosage forms in pharmacy.

In some embodiments of the present invention, the traditional Chinese medicine preparation for treating allergic purpura may be specifically granules, tablets (including dispersible tablets and effervescent tablets), pills (including drop pills), capsules, oral liquids, syrups or external preparations, etc.

In the invention, the pharmaceutically acceptable auxiliary materials refer to conventional pharmaceutical carriers in the pharmaceutical field, and are selected from one or more of fillers, binders, disintegrants, lubricants, suspending agents, wetting agents, pigments, essences, solvents, surfactants or flavoring agents.

The filler is selected from starch, sucrose, lactose, mannitol, sorbitol, xylitol, microcrystalline cellulose or glucose.

The binder is selected from cellulose derivatives, alginates, starch, water, dextrin, gelatin, polyvinylpyrrolidone, or the like.

The disintegrant is selected from microcrystalline cellulose, sodium carboxymethyl starch, crospolyvinylpyrrolidone, low-substituted hydroxypropyl cellulose or croscarmellose sodium.

The lubricant is selected from stearic acid, polyethylene glycol, calcium carbonate, sodium bicarbonate, superfine silica gel powder, talcum powder or magnesium stearate;

the suspending agent is selected from silica gel micropowder, Cera flava, cellulose, and solid polyethylene glycol.

The wetting agent is selected from glycerol, tween-80, ethoxylated hydrogenated castor oil or lecithin.

The solvent is selected from ethanol, liquid polyethylene glycol, isopropanol, tween-80, glycerol, propylene glycol or vegetable oil selected from soybean oil, castor oil, peanut oil, blend oil, etc.

The surfactant is selected from sodium dodecyl benzene sulfonate, stearic acid, polyoxyethylene-polyoxypropylene copolymer, sorbitan fatty acid or polysorbate (Tween) and the like.

The correctant is selected from aspartame, sucralose, essence, steviosin, acesulfame potassium, citric acid or saccharin sodium.

In some embodiments of the present invention, the Chinese medicinal preparation is an oral liquid, wherein the excipients used are selected from xylitol and oligosaccharide, and the pH regulator used is citric acid or sodium salt thereof.

In some embodiments of the present invention, the preparation method of the traditional Chinese medicine preparation for treating allergic purpura comprises: taking the medicinal materials according to the proportion; firstly, water is added into northern glauberite for decoction; adding indigo naturalis (bag decocting), radix Arnebiae, rhizoma Dryopteris Crassirhizomatis, Saviae Miltiorrhizae radix, radix Angelicae Dahuricae, radix Clematidis, and herba Artemisiae Scopariae into the first decoction (A), and decocting with water; obtaining a second decoction (B).

In some embodiments of the present invention, the obtained second decoction (B) can be made into oral liquid or syrup by adding pharmaceutically acceptable adjuvants such as flavoring agent.

In some embodiments of the present invention, the obtained second decoction (B) is further concentrated and may be prepared into an extract. For example, the extract is concentrated to a relative density of 1.10 to 1.25(60 ℃).

In some embodiments of the present invention, the obtained extract can be further made into granules, tablets (including dispersible tablets and effervescent tablets), pills (including drop pills), capsules, oral liquids, syrups or external preparations, etc.

In some embodiments of the present invention, the preparation method of the traditional Chinese medicine preparation for treating allergic purpura comprises the following steps:

1) taking the northern glauber's salt according to the proportion, adding 10-50 times of water by weight for immersing, and decocting for 10-60 min to obtain a decoction;

2) adding indigo naturalis (bag decocting), lithospermum, rhizoma dryopteris crassirhizomae, salvia miltiorrhiza, angelica dahurica, radix clematidis and oriental wormwood into the decoction obtained in the step 1) according to the proportion, adding water with the weight being 8-15 times of that of the medicinal materials, decocting for 1-4 times, decocting for 1-3 hours each time, filtering, and concentrating the filtrate into an extract with the relative density of 1.10-1.25 (60 ℃); or further comprises

3) And (3) taking the extract obtained in the step 2), taking a proper amount of saccharin sodium (serving as spraying liquid), a proper amount of cane sugar and dextrin (serving as bottom materials), and spraying to prepare granules. For example, the granules can be prepared by uniformly spraying in a spray granulator.

Specifically, in step 1), the amount of water added usually requires the immersion of the material; in some embodiments, decocting for 15 min.

Specifically, in the step 2), water is added for decoction for 2 times, and water with the weight being 12 times and 8 times is added for 1 hour each time.

Specifically, in the step 2), the concentration density of the filtrate is 1.10-1.15 (60 ℃).

Specifically, in the step 3), a proper amount of saccharin sodium is added, and preferably, saccharin sodium accounting for 0.04 percent of the weight of the obtained extract is added.

Specifically, in the step 3), the weight ratio of the added sucrose to the dextrin is 2-4: 2, preferably 3:2, and/or the weight sum of the sucrose and the dextrin is preferably 0.15-0.30 times, preferably 0.20-0.25 times of the weight sum of the raw medicinal materials.

In spray granulation, the extract (extractum) has high viscosity and is easy to absorb moisture, so the material is easy to agglomerate; researches find that the problem can be better solved by adjusting the proportion and the dosage of the sucrose and the dextrin.

The invention also comprises the application of the traditional Chinese medicine composition or the traditional Chinese medicine preparation in preparing the medicine for treating anaphylactoid purpura.

The pharmacological action and the traditional Chinese medicine theory of the traditional Chinese medicine composition for treating anaphylactoid purpura are as follows:

indigo naturalis and radix Arnebiae are principal drugs. The indigo naturalis mainly comprises indirubin and indigo as effective components, and has anticancer, pathogenic microorganism resisting, antiinflammatory, analgesic, and liver protecting effects.

The lithospermum is also called as the radix lithospermi, the main effective component of the lithospermum is alkannin, the lithospermum is sweet and salty in taste, cold in nature, beneficial to nine orifices and capable of flowing through water channels, the radix lithospermum is used for treating heat accumulation of internal organs in the ancient times, later people are specially used for treating acne and ulcer, and the normal aim of cooling blood and clearing heat is achieved.

Rhizoma dryopteris crassirhizomae and salvia miltiorrhiza are ministerial drugs, the salvia miltiorrhiza has the effects of activating blood, cooling blood and resolving carbuncle, clearing heat and removing toxicity, and cooling blood and removing stasis, the rhizoma dryopteris crassirhizomae is slightly cold in nature, and the effective component is aspidin, so that the rhizoma dryopteris crassirhizomae has the effects of clearing heat and removing toxicity.

Radix Angelicae Dahuricae, northern gypsum rubrum, radix Clematidis, and herba Artemisiae Scopariae are adjuvant drugs, and radix Angelicae Dahuricae is effective in relieving exterior syndrome, dispelling pathogenic wind, inducing resuscitation, relieving pain, and relieving swelling and pus; northern calcite has the effects of clearing heat and purging fire, inducing resuscitation and relieving swelling, and eliminating dampness and heat edema; the clematis root is used for dispelling wind-damp and dredging the channels and collaterals and is used for treating rheumatic arthralgia; herba Artemisiae Scopariae clears away heat and promotes diuresis, and can be used for treating damp-warm syndrome, eczema and eczema.

The traditional Chinese medicine composition provided by the invention is prepared according to the theory of traditional Chinese medicine, and the dosage of the medicinal materials in the prescription is optimized, so that the original drug effect can be ensured, and the adverse reaction to the gastrointestinal tract can be further reduced. Experiments prove that the traditional Chinese medicine composition provided by the invention has exact curative effect, safety and reliability on allergic purpura which shows skin purpura, bright red or purple red color and is accompanied with symptoms of abdominal pain, arthralgia, dysphoria with smothery sensation, thirst and constipation. The traditional Chinese medicine composition provided by the invention also has the advantages of easily available medicines and low price.

Detailed Description

The following examples are intended to illustrate the invention but are not intended to limit the scope of the invention. The examples do not show the specific techniques or conditions, according to the technical or conditions described in the literature in the field, or according to the product specifications. The reagents or instruments used are conventional products available from regular distributors, not indicated by the manufacturer.