Application of traditional Chinese medicine composition in preparation of medicine for treating or preventing systemic lupus erythematosus

Abstract

The invention provides application of a traditional Chinese medicine composition in preparation of a medicine for treating or preventing systemic lupus erythematosus. The traditional Chinese medicine composition comprises the following components in parts by weight: 1-100 parts of mangnolia officinalis, 1-100 parts of scorched betel nut, 1-100 parts of roasted amomum tsao-ko, 1-100 parts of ephedra, 1-100 parts of semen armeniacae amarae, 1-100 parts of notopterygium root, 1-100 parts of ginger, 1-100 parts of pogostemon cablin, 1-100 parts of eupatorium, 1-100 parts of rhizoma atractylodis, 1-160 parts of poria cocos, 1-120 parts of bighead atractylodes rhizome, 1-100 parts of gypsum, 1-100 parts of scorched hawthorn fruit, 1-100 parts of scorched medicated leaven, 1-100 parts of scorched malt, 1-100 parts of earthworm, 1-100 parts of cynanchum paniculatum, 1-100 parts The traditional Chinese medicine composition can reduce the content of urine protein and the anti-ds-DNA and ANA level of mice, alleviates the degree of kidney fatigue of the mice, and has an obvious protection effect on norphytane induced systemic lupus erythematosus mice.

Description

Technical Field

[0001] The present application belongs to the technical field of traditional Chinese medicine, and specifically relates to the use of a traditional Chinese medicine composition in the preparation of a medicine for treating or preventing systemic lupus erythematosus. Background Art

[0002] Systemic lupus erythematosus (SLE) is an autoimmune disease involving multiple systems and organs. Its clinical manifestations are complex and diverse, and its etiology is still unknown. A large number of studies have shown that genetics, viral infection, endocrine disorders, immune abnormalities and some environmental factors are related to the onset of this disease. The age of onset of this disease is mostly 20 to 40 years old, and it is more common in young and middle-aged women of childbearing age. The clinical symptoms are relatively complex, the disease progresses rapidly and is difficult to cure. It can involve multiple organ systems, seriously affecting the patient's life, health and quality of life. At present, the mainstream drugs for the treatment of SLE are glucocorticoids and immunosuppressants, but long-term use of hormones and immunosuppressants will inevitably bring some serious side effects, such as hyperlipidemia, hypertension, peptic ulcers, atherosclerosis, osteoporosis, femoral head necrosis, liver function damage, bone marrow suppression and secondary infection, which poses a great hidden danger to the safety of patient treatment. There is no name for systemic lupus erythematosus in traditional medical literature, but its clinical manifestations are described in similar ways in the literature, such as "sunburn sores", "butterfly dan", "yin and yang poison", etc. The internal cause is insufficient congenital endowment, and the external cause is careless living, exposure to sunlight, exposure to evil toxins, internal injuries caused by the seven emotions, excessive labor and desire, etc., which lead to imbalance of yin and yang in the internal organs, toxic heat and blood stasis, and the onset of the disease. Therefore, Chinese medicine believes that its basic pathogenesis is congenital deficiency, which is based on kidney yin deficiency or acquired malnutrition, leading to the generation of damp heat and blood stasis. Blood stasis and toxic heat are the main pathogenesis of systemic lupus erythematosus.

[0003] Traditional Chinese medicine has a strong anti-inflammatory and anti-inflammatory effect in the treatment of systemic lupus erythematosus, and can reduce the side effects of immunosuppressants and the incidence of infected tumors. Traditional Chinese medicine also has the function of resisting the side effects of hormones. In addition, traditional Chinese medical care is also of great help in the treatment of systemic lupus erythematosus. Therefore, traditional Chinese medicine has obvious characteristics and advantages in alleviating patients' clinical symptoms, reducing the toxic and side effects and dosage of Western medicine, and improving patients' quality of life, and obtains better therapeutic effects. The development of a Chinese medicine composition for the treatment of systemic lupus erythematosus has significant social benefits. Summary of the invention

[0004] TCM treatment of systemic lupus erythematosus is to restore the body's internal balance or the balance with the external environment, and to carry out syndrome differentiation and treatment guided by the holistic concept. It is people-oriented, highly individualized and targeted, and has no side effects. In addition, TCM treatment emphasizes syndrome differentiation and treatment, and uses medicines for each patient and different conditions. The medicinal materials used are all pure natural herbs and minerals, hygienic and environmentally friendly, with few toxic side effects, stable quality, and relatively low price.

[0005] Based on the above advantages of traditional Chinese medicine, in order to solve the technical problems of the above-mentioned systemic lupus erythematosus treatment, the present application provides a Chinese medicine composition for the preparation of a drug for treating or preventing systemic lupus erythematosus, the Chinese medicine composition comprising: 1-100 parts of Magnolia officinalis, 1-100 parts of scorched Areca catechu, 1-100 parts of simmered Tsaoko fruit, 1-100 parts of Ephedra, 1-100 parts of Bitter Apricot, 1-100 parts of Notopterygium wilfordii, 1-100 parts of Ginger, 1-100 parts of Patchouli, 1-100 parts of Cyperus rotundus, 1-100 parts of Atractylodes macrocephala, 1-160 parts of Poria cocos, 1-120 parts of Atractylodes macrocephala, 1-100 parts of Gypsum, 1-100 parts of scorched Crataegus pinnatifida, 1-100 parts of scorched Liu Shenqu, 1-100 parts of scorched malt, 1-100 parts of Pheretima, 1-100 parts of Cynanchum wilfordii, 1-100 parts of Cynomorium fortunei, and 1-100 parts of Lepidium chinense. The application may be any form that is beneficial to improving the corresponding symptoms of the patient, including treatment or prevention.

[0006] Furthermore, the Chinese medicine composition includes: 10-80 parts of Magnolia officinalis, 10-80 parts of scorched betel nut, 10-80 parts of stewed tsaoko, 10-60 parts of ephedra, 10-60 parts of bitter almond, 10-80 parts of Notopterygium wilfordii, 10-60 parts of ginger, 10-80 parts of patchouli, 10-60 parts of Cyperus rotundus, 10-80 parts of Atractylodes macrocephala, 10-160 parts of Poria cocos, 10-120 parts of Atractylodes macrocephala, 10-80 parts of gypsum, 10-50 parts of scorched hawthorn, 10-80 parts of scorched Liu Shenqu, 10-60 parts of scorched malt, 10-80 parts of earthworms, 10-80 parts of Cynanchum chinense, 10-60 parts of Cynomorium fortunei, and 10-80 parts of Lemongrass seeds.

[0007] Optionally, the Chinese medicine composition includes: 30-50 parts of Magnolia officinalis, 20-30 parts of scorched Areca catechu, 30-50 parts of stewed Tsaoko fruit, 20-30 parts of Ephedra sinica, 20-30 parts of Bitter Apricot, 30-50 parts of Notopterygium wilfordii, 30-50 parts of Ginger, 30-50 parts of Patchouli, 20-30 parts of Cyperus rotundus, 30-50 parts of Atractylodes macrocephala, 120-150 parts of Poria cocos, 80-100 parts of Atractylodes macrocephala, 30-50 parts of Gypsum, 20-30 parts of scorched Crataegus pinnatifida, 30-50 parts of scorched Liu Shenqu, 20-30 parts of scorched malt, 30-50 parts of Pheretima, 30-50 parts of Cynanchum cyrtonema, 20-30 parts of Cyperus rotundus, and 30-50 parts of Lepidium glutamate.

[0008] Specifically, the Chinese medicine composition can also be: 50 parts of Magnolia officinalis, 30 parts of scorched betel nut, 30 parts of stewed tsaoko, 20 parts of ephedra, 30 parts of bitter almond, 50 parts of Notopterygium wilfordii, 50 parts of ginger, 50 parts of patchouli, 30 parts of Cyperus rotundus, 50 parts of Atractylodes macrocephala, 150 parts of Poria cocos, 100 parts of Atractylodes macrocephala, 50 parts of gypsum, 30 parts of scorched hawthorn, 30 parts of scorched Liu Shenqu, 30 parts of scorched malt, 50 parts of earthworm, 50 parts of Cynomorium wilfordii, 30 parts of Cynomorium fortunei, and 50 parts of Lemongrass seeds.

[0009] The above-mentioned composition can be directly ground into powder by raw materials, or can be an extract or other forms prepared by any conventional means.

[0010] Specifically, the aforementioned drugs for treating systemic lupus erythematosus include oral dosage forms, injectable dosage forms or external dosage forms.

[0011] After weighing the raw materials in proportion according to the dosage form of the drug, pharmaceutically acceptable excipients such as fillers, disintegrants, lubricants, suspending agents, adhesives, sweeteners, flavoring agents, preservatives, bases, etc. are added during the preparation, and the drug is prepared according to conventional production methods in the pharmaceutical field to prepare conventional dosage forms acceptable to pharmacy, including but not limited to decoctions, granules, capsules, tablets, oral liquids, pills, tinctures, syrups, suppositories, gels, sprays, and injections.

[0012] The present application also provides a method for preparing any of the aforementioned Chinese medicine compositions, the preparation method comprising: weighing Magnolia officinalis, scorched areca nut, stewed tsaoko, ephedra, bitter almond, Notopterygium wilfordii, ginger, patchouli, Cymbidium orchioides, Atractylodes lancea, Poria cocos, Atractylodes macrocephala, gypsum, scorched hawthorn, scorched Liushenqu, scorched malt, earthworm, Cynanchum chinense, Cynomorium fortunei, and Semen Lepidium chinense respectively according to the formula, extracting twice with water, adding 6 times the amount of water for the first time and extracting for 1.5 hours, adding 4 times the amount of water for the second time and extracting for 1.0 hour, combining the extracts, filtering, concentrating the filtrate to a relative density of 1.10 to 1.15, centrifuging and filtering, vacuum drying the filtrate, spray drying and pulverizing to obtain the product.

[0013] Furthermore, the preparation method of the above-mentioned Chinese medicine composition granules comprises the following steps:

[0014] According to the formula, 50 parts of Magnolia officinalis, 30 parts of charred Areca nut, 30 parts of stewed Tsaoko fruit, 20 parts of Ephedra, 30 parts of Bitter Apricot, 50 parts of Notopterygium, 50 parts of Ginger, 50 parts of Patchouli, 30 parts of Perilla frutescens, 50 parts of Atractylodes, 150 parts of Poria, 100 parts of Atractylodes, 50 parts of Gypsum, 30 parts of charred Crataegus, 30 parts of charred Liu Shenqu, 30 parts of charred Malt, 50 parts of Pheretima, 50 parts of Cynanchum wilfordii, 30 parts of Cynomorium fortunei, and 50 parts of Semen Lepidii were respectively taken, and water was added for reflux extraction twice, 6 times of water was added for the first time, and the extraction was carried out for 1.5 hours, and 4 times of water was added for the second time, and the extraction was carried out for 1.0 hour. The extracts were combined, filtered, and the filtrate was concentrated to a relative density of 1.10-1.15, centrifuged and filtered, and the filtrate was vacuum dried and spray dried to obtain an intermediate composition, and sucralose and dextrin were added, mixed, and granules were obtained.

[0015] Advantageous Effects of the Invention

[0016] The Chinese medicine composition provided in the present application can significantly reduce the urine protein content in the systemic lupus erythematosus mouse model induced by pristane, and alleviate the degree of kidney involvement in mice; significantly reduce the levels of anti-ds-DNA (anti-double-stranded DNA antibodies) and ANA (anti-nuclear antibodies), and has a significant protective effect on the systemic lupus erythematosus mouse model induced by pristane, indicating that the Chinese medicine composition has a certain therapeutic effect on systemic lupus erythematosus. DETAILED DESCRIPTION

[0017] The present application aims to provide an application of a Chinese medicine composition in the preparation of a drug for treating or preventing systemic lupus erythematosus. In order to enable those skilled in the art to more clearly understand the technical solution of the present application, the technical solution of the present application will be described in detail below in conjunction with specific embodiments. The following experiments, if no specific conditions are specified, are carried out according to conventional conditions or conditions recommended by the manufacturer, and the raw materials or excipients used, as well as the reagents or instruments used, if the manufacturer is not specified, are all conventional products that can be obtained commercially. The experimental methods for which the detailed conditions are not specified are carried out in accordance with conventional test methods or in accordance with the operating instructions recommended by the supplier.

[0018] It should be noted that the following detailed description is illustrative and is intended to provide further explanation of the present application. Unless otherwise specified, all technical and scientific terms used herein have the same meanings as those generally understood by those of ordinary skill in the art to which the present application belongs. The following examples are only intended to further illustrate the technical solution of the present application, rather than to limit the scope of protection of the present application.

[0019] Example 1 Preparation of Composition Granules

[0020] According to the formula, the following raw materials were weighed respectively: 50 parts of Magnolia officinalis, 30 parts of scorched areca nut, 30 parts of stewed tsaoko fruit, 20 parts of ephedra, 30 parts of bitter almond, 50 parts of Notopterygium wilfordii, 50 parts of ginger, 50 parts of patchouli, 30 parts of eupatorium, 50 parts of atractylodes, 150 parts of Poria, 100 parts of Atractylodes macrocephala, 50 parts of gypsum, 30 parts of scorched hawthorn, 30 parts of scorched six Shenqu, 30 parts of scorched malt, 50 parts of earthworm, 50 parts of Cynanchum chinense, 30 parts of Cynomorium mongolicum, and 50 parts of Lemongrass seeds. Add water to the above-weighed medicinal materials and reflux extract twice. For the first time, add 6 times of water and extract for 1.5 hours. For the second time, add 4 times of water and extract for 1.0 hour. Combine the extracts, filter, concentrate the filtrate to a relative density of 1.10-1.15, centrifuge and filter, vacuum dry the filtrate, spray dry and pulverize to obtain an intermediate, add sucralose and dextrin, mix well, and obtain granules.

[0021] Experimental Example 1 Effect on Urinary Protein in Systemic Lupus Erythematosus Mouse Model

[0022] Establishment of animal model: After 36 SPF-grade BALB / c female mice aged 6 to 8 weeks and weighing 18 to 22 g were adaptively raised in an SPF environment for 7 days, 6 mice were randomly selected as the control group using a random number table method and fed with normal feed and drinking water. The remaining 30 mice were used for modeling and given a one-time intraperitoneal injection of 0.5 mL of pristane (Shanghai Yuanye Biotechnology Co., Ltd., 100 mL, Product No. S44062) for modeling, and the control group was given a one-time intraperitoneal injection of 0.5 mL of normal saline.

[0023] 24 hours after modeling, the mice were randomly divided into model group, high, medium and low dose groups of the composition (the composition was prepared in Example 1), and prednisone acetate group (Zhejiang Xianjun Pharmaceutical Co., Ltd., specification: 5mg*100 tablets / box, product batch number: LA22243), with 6 mice in each group. According to the clinical usage and dosage of prednisone tablets for adults: 5-10 mg (1-2 tablets) orally once, 10-60 mg (2-12 tablets) a day. The adult body weight is calculated as 60 kg, so the daily dosage for adults is 60 mg / 60 kg=1 mg / kg. The equivalent amount for mice is 1 mg / kg×9.1=9.1 mg / kg. According to the calculated dosage, mice in each administration group were gavaged once a day, 5 times a week, and the overall test period was 6 months. The dosage of mice was 0.1 mL / 10 g gavage each time according to the weight of the animal. The control group and the model group were both gavaged with the same volume of distilled water every day, once a day, 5 times a week, and the overall test period was 6 months.

[0024] After mice were injected with pristane or saline, urine protein was measured once a month using urine protein test strips (Guilin Ulite Medical Electronics Co., Ltd., batch number 20152400047). The urine protein content range (g / L) was determined by comparing the color development of the reaction area of ​​the test strip with the standard color plate of the test strip: (-): 0; (±): 0.15-0.30; (+): 0.30-1.00; (++): 1.00-3.00; (+++): 3.00-5.00; (++++): ≥5.00.

[0025] The experimental results showed that the amount of urine protein in the control group was ≤±, and did not increase over time. The model group began to have proteinuria one month after the injection of pristane, and most of them were ++ or +++, indicating that the model was successfully established. The combination of medium and high dose groups showed significant improvement compared with the model group, and most of them were ± or +, as shown in Table 1.

[0026] Table 1 Mouse urine protein tracking monitoring data

[0027]

[0028]

[0029] Note: The occurrence rate refers to the ratio of the number of mice judged as (-), (±), (+), (++), (+++), (++++) according to the color development degree of the test paper reaction area after judging the urine protein content to the total number of mice in the group.

[0030] Experimental Example 2 Effects on Anti-ds-DNA and ANA in Serum of Systemic Lupus Erythematosus Mouse Model

[0031] The establishment of the mouse model and the administration method were the same as those in Example 1. At 1, 2, 3, 4, 5, and 6 months after the mice were intraperitoneally injected with pristane or saline, peripheral blood was collected from the orbital venous plexus of the mice, and centrifuged (3500r / min) for 12min (refrigerated centrifuge, eppendorf, 5804R) after standing for 2 hours at 4°C. The serum was transferred to EP tubes respectively, and the anti-double-stranded DNA antibody (ds-DNA) ELISA kit (Shanghai Yanjin Biotechnology Co., Ltd., item number: F02112) and the anti-nuclear antibody (ANA) ELISA detection kit (Shanghai ELISA Biotechnology, item number: ml002245) were used according to the instructions of each kit. The anti-ds-DNA and ANA concentrations were measured once a month, and the values ​​were read using an ELISA reader (Molecular Devices), and a total of 6 measurements were made. GraphPadprism 7 statistical software was used for data processing, and all data were expressed as mean ± standard deviation. One-way ANOVA combined with Dunnett's multiple comparison test was used for statistical analysis of the data, and P < 0.05 indicated that the data were statistically significant.

[0032] The experimental results showed that compared with the normal control group, the anti-ds-DNA concentration of mice in the model group was significantly higher than that in the control group (P < 0.001). Compared with the model group, the medium and high dose groups of the composition can significantly reduce the anti-ds-DNA concentration of mice (P < 0.05, P < 0.01, P < 0.001). For ANA, compared with the normal control group, the ANA concentration of mice in the model group was significantly higher than that in the control group (P < 0.001). Compared with the model group, the medium and high dose groups of the Chinese medicine composition can significantly reduce the ANA concentration of mice (P < 0.05, P < 0.001). The results are shown in Tables 2 and 3.

[0033] Table 2 Anti-ds-DNA concentration

[0034]

[0035] Note: Compared with the blank control group, ### P<0.001; compared with the model group, ** P<0.01, *** P<0.001.

[0036] Table 3 ANA concentration

[0037]

[0038] Note: Compared with the blank control group, ### P<0.001; compared with the model group, * P<0.05, ** P<0.01, *** P<0.001.

[0039] The Chinese medicine composition proposed in the present application can significantly reduce the urine protein content of model animals and reduce the levels of anti-ds-DNA and ANA.

[0040] The above embodiments of the present application are only for the purpose of clearly illustrating the examples made by the present application, and are not intended to limit the implementation methods of the present application. For those of ordinary skill in the art, other different forms of changes or modifications can also be made on the basis of the above description. It is not necessary and impossible to list all the implementation methods here. Any modifications, equivalent substitutions and improvements made within the spirit and principles of the present application should be included in the protection scope of the claims of the present application.

Claims

1. Use of a Chinese medicine composition in the preparation of a medicament for treating or preventing systemic lupus erythematosus, characterized in that: The Chinese medicine composition comprises: 1-100 parts of Magnolia officinalis, 1-100 parts of charred Areca catechu, 1-100 parts of stewed Tsaoko fruit, 1-100 parts of Ephedra, 1-100 parts of bitter almond, 1-100 parts of Notopterygium wilfordii, 1-100 parts of ginger, 1-100 parts of Patchouli, 1-100 parts of Cyperus rotundus, 1-100 parts of Atractylodes macrocephala, 1-160 parts of Poria cocos, 1-120 parts of Atractylodes macrocephala, 1-100 parts of Gypsum, 1-100 parts of charred Crataegus pinnatifida, 1-100 parts of charred Liu Shenqu, 1-100 parts of charred malt, 1-100 parts of Pheretima, 1-100 parts of Cynanchum cyrtonema, 1-100 parts of Lepidium chinense.

2. The use according to claim 1, characterized in that: The Chinese medicine composition comprises: 10-80 parts of Magnolia officinalis, 10-80 parts of scorched Areca catechu, 10-80 parts of stewed Tsaoko fruit, 10-60 parts of Ephedra sinica, 10-60 parts of Bitter Apricot, 10-80 parts of Notopterygium wilfordii, 10-60 parts of Ginger, 10-80 parts of Patchouli, 10-60 parts of Cyperus rotundus, 10-80 parts of Atractylodes macrocephala, 10-160 parts of Poria cocos, 10-120 parts of Atractylodes macrocephala, 10-80 parts of Gypsum, 10-50 parts of scorched Crataegus pinnatifida, 10-80 parts of scorched Liu Shenqu, 10-60 parts of scorched malt, 10-80 parts of Pheretima, 10-80 parts of Cynanchum cyrtonema, 10-60 parts of Lepidium chinense, and 10-80 parts of Semen Lepidii.

3. The use according to claim 2, characterized in that: The Chinese medicine composition comprises: 30-50 parts of Magnolia officinalis, 20-30 parts of scorched Areca catechu, 30-50 parts of stewed Tsaoko fruit, 20-30 parts of Ephedra sinica, 20-30 parts of Bitter Apricot, 30-50 parts of Notopterygium wilfordii, 30-50 parts of Ginger, 30-50 parts of Patchouli, 20-30 parts of Cyperus rotundus, 30-50 parts of Atractylodes macrocephala, 120-150 parts of Poria cocos, 80-100 parts of Atractylodes macrocephala, 30-50 parts of Gypsum, 20-30 parts of scorched Crataegus pinnatifida, 30-50 parts of scorched Liu Shenqu, 20-30 parts of scorched malt, 30-50 parts of Pheretima, 30-50 parts of Cynanchum cyrtonema, 20-30 parts of Cynomorium wilfordii, and 30-50 parts of Lepidium chinense.

4. The use according to any one of claims 1 to 3, characterized in that: The dosage form of the systemic lupus erythematosus drug includes an oral dosage form, an injection dosage form or an external administration preparation.

5. The use according to claim 4, characterized in that: The dosage forms of the systemic lupus erythematosus drug include decoction, granules, capsules, tablets, oral liquid, pills, tincture, syrup, gel, spray and injection.

6. The use according to any one of claims 1 to 3, characterized in that: The preparation method of the traditional Chinese medicine composition comprises: weighing Magnolia officinalis, charred Areca nut, stewed tsaoko, ephedra, bitter almond, Notopterygium wilfordii, ginger, patchouli, Perilla frutescens, Atractylodes lancea, Poria cocos, Atractylodes macrocephala, gypsum, charred hawthorn, charred Liushenqu, charred malt, earthworm, Cynanchum chinense, Cynomorium fortunei, and Semen tiliaceum according to the formula, adding water for reflux extraction twice, combining the extracts, filtering, concentrating the filtrate, filtering, drying, and crushing to obtain the composition.

7. The use according to claim 6, characterized in that: The preparation method of the traditional Chinese medicine composition comprises: adding 6 times of water in the first reflux extraction and extracting for 1.5 hours, adding 4 times of water in the second reflux extraction and extracting for 1.0 hour; combining the two extracts and filtering them, concentrating them to a relative density of 1.10-1.15, centrifugally filtering, vacuum drying the filtrate, spray drying and crushing to obtain the composition.

8. The use according to any one of claims 1 to 3, characterized in that: The preparation method of the Chinese medicine composition granules comprises: according to the formula, respectively weighing Magnolia officinalis, charred Areca nut, stewed tsaoko, ephedra, bitter almond, Notopterygium wilfordii, ginger, patchouli, Perilla frutescens, Atractylodes lancea, Poria cocos, Atractylodes macrocephala, gypsum, charred hawthorn, charred Liushenqu, charred malt, earthworm, Cynanchum chinense, Cynomorium mianmai, and Semen tiliaceum, adding water and refluxing to extract twice, adding 6 times of water for the first time and extracting for 1.5 hours, adding 4 times of water for the second time and extracting for 1.0 hour, combining the extracts, filtering, concentrating the filtrate to a relative density of 1.10-1.15, centrifuging, vacuum drying the filtrate, spray drying and pulverizing to obtain an intermediate composition, adding sucralose and dextrin, mixing evenly, and obtaining granules.

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