Application of traditional Chinese medicine composition in preparation of medicine for rheumatoid arthritis

Abstract

The invention relates to an application of a traditional Chinese medicine composition in preparation of a medicine for rheumatoid arthritis, which is characterized in that the traditional Chinese medicine composition is prepared from astragalus membranaceus, dried ginger, salted morinda officinalis, cortex dictamni, calcined oyster shell, schisandra chinensis and divaricate saposhnikovia root. The composition can significantly reduce the arthritis index score of rheumatoid arthritis model rats and mice, significantly reduce the spleen and thymus indexes of the model rats and the content of TNF-alpha and IL-6 in serum, and significantly reduce the foot swelling of the model mice, and has a good treatment effect on rheumatoid arthritis.

Description

Technical Field

[0001] The present invention belongs to the technical field of traditional Chinese medicines, relates to a new use of a traditional Chinese medicine composition, and particularly relates to the use of the traditional Chinese medicine composition in preparing a medicine for rheumatoid arthritis. Background Art

[0002] Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease characterized by erosive, symmetrical arthritis. RA can occur at any age, with 80% developing between the ages of 35 and 50, and a male-to-female prevalence ratio of approximately 1:4. Its etiology and pathogenesis are complex. Under the combined influence of multiple factors, including genetics, infection, and the environment, autoimmune responses drive immune damage and repair, fundamental to the development and progression of RA. The clinical manifestations of RA vary greatly from person to person. Most cases present with a chronic onset, characterized by symmetrical swelling and pain in multiple joints, including the hands, wrists, and feet. These symptoms are often accompanied by morning stiffness, fatigue, low-grade fever, muscle aches, and weight loss, among other systemic symptoms. In some cases, the onset is acute, with typical joint symptoms appearing within a few days. As the disease progresses, articular cartilage and bone destruction gradually occur, ultimately leading to joint deformity and loss of function. This disease is prevalent worldwide, not only impairing physical function and quality of life for patients but also placing a significant economic burden on their families and society, making it a leading cause of disability and work-related loss. In view of the above problems, the field of traditional Chinese medicine should actively participate in the prevention and treatment of rheumatoid arthritis and develop appropriate prescriptions. Summary of the Invention

[0003] The technical problem to be solved by the present invention is to provide an oral medicine for treating rheumatoid arthritis, which has a significant effect in treating rheumatoid arthritis.

[0004] The technical solutions of the present invention for solving the above problems are as follows:

[0005] A Chinese medicine composition for use in preparing a remedy for rheumatoid arthritis, wherein the use can be any form beneficial for improving the patient's corresponding symptoms, including treatment or prevention. The Chinese medicine composition is made from the following components: 5-15 parts of dried ginger, 15-25 parts of astragalus root, 5-15 parts of salt-cured Morinda officinalis root, 5-15 parts of Dictamni root bark, 25-35 parts of calcined oyster shell, 5-10 parts of Schisandra chinensis fruit, and 5-15 parts of Saposhnikovia divaricata. The composition of the present invention can be directly ground into a powder or can be an extract prepared by conventional means in the art. The Chinese medicines used in the composition of the present invention can also be used in the form of directly ground into a powder, an extract, or other processed forms.

[0006] The present invention also provides an application of a traditional Chinese medicine composition in the preparation of an anti-inflammatory drug, wherein the inflammation may be inflammation caused by rheumatoid arthritis.

[0007] Furthermore, the Chinese medicine composition is made of the following components: 9-11 parts of dried ginger, 19-23 parts of astragalus, 9-11 parts of salt Morinda officinalis, 9-11 parts of Dictamni cortex, 28-34 parts of calcined oyster shell, 6-7 parts of Schisandra chinensis, and 9-11 parts of Saposhnikovia divaricata.

[0008] Furthermore, the Chinese medicine composition is prepared from the following components: 10 parts of dried ginger, 20 parts of astragalus root, 10 parts of salt Morinda officinalis root, 10 parts of white peony root, 30 parts of calcined oyster shell, 6 parts of Schisandra chinensis, and 10 parts of siler. Furthermore, the preparation method of the aforementioned Chinese medicine composition includes:

[0009] Take dried ginger, salt Morinda officinalis, Astragalus membranaceus, Dictamni cortex, calcined oyster shell, Schisandra chinensis and Saposhnikovia divaricata, add 10 times the amount of water, decoct twice, each time for 1 hour, filter, combine the filtrate, concentrate to a clear paste with a relative density of 1.07-1.15 (60℃), spray dry, and obtain dry paste powder.

[0010] Specifically, the drug includes pharmaceutically acceptable excipients or additives.

[0011] Specifically, the pharmaceutically acceptable excipients or additives include fillers, disintegrants, lubricants, suspending agents, binders, sweeteners, flavoring agents, preservatives, and bases.

[0012] Specifically, the pharmaceutical dosage forms of the drug provided by the present invention include oral dosage forms, injection dosage forms or external dosage forms.

[0013] The dosage forms of the drugs of the present invention are prepared by weighing the raw materials in proportion, adding pharmaceutically acceptable excipients or additives, such as fillers, disintegrants, lubricants, suspending agents, binders, sweeteners, flavoring agents, preservatives, bases, etc., and preparing according to conventional production methods in the pharmaceutical field to prepare conventional pharmaceutically acceptable dosage forms, including but not limited to decoctions, granules, capsules, tablets, oral liquids, pills, soft capsules, dripping pills, tinctures, syrups, suppositories, gels, sprays, and injections.

[0014] The medicine of the present invention can be prepared by the following method:

[0015] Take 10kg of dried ginger, 10kg of salt Morinda officinalis, 20kg of Astragalus membranaceus, 10kg of Dictamnus cortex, 30kg of calcined oyster shell, 6kg of Schisandra chinensis and 10kg of Saposhnikovia divaricata, add 10 times the amount of water, decoct twice, each time for 1 hour, filter, combine the filtrate, concentrate to a clear paste with a relative density of 1.07-1.15 (60°C), spray dry to obtain a Chinese medicine composition intermediate, add dextrin, mix well, granulate with 90% ethanol, dry, and granulate to obtain the product.

[0016] The medicine of the present invention is a conventional granule, tablet or capsule.

[0017] The composition of the present invention can significantly reduce the arthritis index scores of rheumatoid arthritis model rats and mice, significantly reduce the spleen and thymus indexes of model rats and the TNF-α and IL-6 levels in serum, and significantly reduce foot swelling in model mice, and has a good therapeutic effect on rheumatoid arthritis. DETAILED DESCRIPTION

[0018] As mentioned above, the present invention aims to provide a use of a Chinese medicine composition in the preparation of a medicament for rheumatoid arthritis, which will be described in detail below in conjunction with specific experimental content.

[0019] Unless otherwise specified, the following experiments were conducted under conventional conditions or those recommended by the manufacturer. All APIs, excipients, reagents, and instruments used, unless the manufacturer is specified, are commercially available. Unless otherwise specified, all percentages, ratios, proportions, and parts are by weight.

[0020] Unless otherwise defined, all professional and scientific terms used herein have the same meaning as those familiar to those skilled in the art. In addition, any methods and materials similar or equivalent to those described herein can be applied to the present invention.

[0021] Example 1 Preparation of granules of the composition of the present invention

[0022] Take 10kg of dried ginger, 10kg of salt Morinda officinalis, 20kg of Astragalus membranaceus, 10kg of Dictamnus cortex, 30kg of calcined oyster shell, 6kg of Schisandra chinensis and 10kg of Saposhnikovia divaricata, add 10 times the amount of water, decoct twice, each time for 1 hour, filter, combine the filtrate, concentrate to a clear paste with a relative density of 1.07-1.15 (60°C), spray dry to obtain a Chinese medicine composition intermediate, add dextrin, mix well, granulate with 90% ethanol, dry, and granulate to obtain the product.

[0023] Example 2 Therapeutic Effect of Chinese Medicine Composition on Rheumatoid Arthritis Model Rats

[0024] 1. Experimental Materials

[0025] 1.1 Animals

[0026] 60 Wistar rats, SPF grade, male, 150-180 g.

[0027] Breeding environment: room temperature 20-26℃, relative humidity controlled at 40-70%, 5 birds per cage.

[0028] 1.2 Medication

[0029] Chinese medicine composition, intermediate prepared according to the method of Example 1, Jiangsu Kangyuan Pharmaceutical Co., Ltd.; dexamethasone acetate tablets, Chenxin Pharmaceutical Co., Ltd., batch number: 2204070213.

[0030] 1.3 Reagents

[0031] Chicken type II collagen, Chondrex, USA, batch number: 20012; complete Freund's adjuvant, Chondrex, USA, batch number: 7001; rat TNF-α ELISA kit, Xinbosheng Biotechnology Co., Ltd., batch number: R220617-102b; rat IL-6 ELISA kit, Xinbosheng Biotechnology Co., Ltd., batch number: R220617-003b.

[0032] 1.4 Instruments

[0033] Electronic balance, Mettler-Toledo, Switzerland, model: ME104E; multi-mode micropore detection system, MD Company, USA, model: Flex Station 3.

[0034] 2. Dosage design

[0035] Based on the clinical adult (60 kg) dose of 96 g of crude drug per day, the equivalent rat dose, calculated using the body surface area method, is 9.0 g / kg. Using a 1 / 4:1 / 2:1 dosing regimen, the low dose of the Chinese medicine composition is 4.5 mg / kg, and the medium dose is 2.25 g / kg.

[0036] Dexamethasone acetate tablets, 0.75 mg / tablet, the clinical dose for adults (60 kg) is 4.5 mg / day. The equivalent dose for rats calculated according to the body surface area method is 0.42 mg / kg.

[0037] 3. Experimental Methods

[0038] Wistar rats were adapted to feeding for one week with free access to feed and water. All rats, except for the normal control group, were anesthetized with gas, and after alcohol disinfection of the right hind paw, 0.1 mL of the modeling agent (bovine type II collagen solution (V): complete Freund's adjuvant (V) = 1:1) was intradermally injected. The normal control group was injected with an equal volume of normal saline. On day 14 of modeling, successful modeling was determined based on an arthritis index score (sum of scores across all four limbs) ≥ 4. The established model rats were then divided evenly into five groups: a model control group, a dexamethasone acetate group, and low-, medium-, and high-dose groups of the traditional Chinese medicine composition, with 10 rats in each group. Each group received the corresponding drug by oral gavage at a volume of 10 mL / kg once daily for 28 consecutive days. The normal and model control groups were given distilled water under the same conditions.

[0039] After successful modeling, the arthritis index was observed every 7 days, and the rats were scored for the arthritis index (AI) using a five-level scoring method. The scoring criteria are shown in Table 1.

[0040] Table 1: Arthritis Index (AI) scoring criteria

[0041]

[0042] After the last day of administration, the rats were weighed and anesthetized. Blood was collected from the abdominal aorta, and then the spleen and thymus were removed. The surrounding fat was removed, the blood stains on the surface were blotted dry, and the rats were weighed. The spleen and thymus indexes were calculated using the following formula:

[0043] Spleen index (%) = spleen weight (g) / body weight (g) * 100%;

[0044] Thymus index (%) = thymus weight (g) / body weight (g) * 100%.

[0045] The blood was placed at room temperature for 1 hour and then centrifuged for 10 minutes (3000 rpm). The supernatant was then carefully aspirated. The TNF-α and IL-6 levels in rat serum were determined according to the ELISA kit instructions. The TNF-α and IL-6 concentrations in the serum samples of each group of rats were calculated.

[0046] 4. Statistical methods

[0047] The results were statistically analyzed using t-test.

[0048] 5. Experimental Results

[0049] 5.1 Effect on the Arthritis Index Score of Rheumatoid Arthritis Model Rats

[0050] After the rats were injected with the modeling agent, the arthritis index scores of the rats were significantly increased compared with the normal control group, with a statistically significant difference (P<0.01); the arthritis index scores of the rats in the model control group gradually decreased with time; the drug was administered starting from the 14th day of modeling, once a day, for 28 consecutive days. Compared with the model control group at each time point, the arthritis index scores of the low, medium and high dose groups of the Chinese medicine composition were significantly reduced (P<0.01), as shown in Table 2 for details.

[0051] Table 2: Therapeutic effects on arthritis index scores in rheumatoid arthritis model rats

[0052]

[0053] Note: Compared with the normal control group, ## P<0.001; compared with the model control group, *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001.

[0054] 5.2 Effects on spleen and thymus index in rheumatoid arthritis model rats

[0055] After the rats were injected with the modeling agent, the arthritis index, spleen and thymus index of the rats were significantly increased compared with the normal control group, with statistically significant differences (P<0.01); after 28 days of continuous administration, the spleen index and thymus index of the low, medium and high dose groups of the Chinese medicine composition were significantly decreased compared with the model control group (P<0.01), as shown in Table 3 for details.

[0056] Table 3: Effects on spleen and thymus index in rheumatoid arthritis model rats

[0057]

[0058] Note: Compared with the normal control group, ## P<0.001; compared with the model control group, **P<0.01.

[0059] 5.3 Effects on serum TNF-α and IL-6 levels in rheumatoid arthritis model rats

[0060] After the rats were injected with the modeling agent, the serum levels of TNF-α and IL-6 were significantly increased compared with the normal control group, with statistical differences (P<0.01); after 28 days of continuous administration, the low, medium and high doses of the Chinese medicine composition significantly reduced the levels of TNF-α and IL-6 compared with the model control group, with statistical differences (P<0.01), as shown in Table 4 for details.

[0061] Table 4: Effects on serum TNF-α and IL-6 levels in rheumatoid arthritis model rats

[0062]

[0063] Note: Compared with the normal control group, ## P<0.001; compared with the model control group, **P<0.01, ***P<0.001.

[0064] 6. Experimental Conclusion

[0065] The Chinese medicine composition at doses of 2.25, 4.5 and 9.0 g crude drug / kg can significantly inhibit the arthritis index score of rheumatoid arthritis model rats, and significantly reduce the spleen and thymus indexes of the model rats and the TNF-α and IL-6 levels in the serum, suggesting that the Chinese medicine composition has a certain therapeutic effect on rheumatoid arthritis and related inflammation.

[0066] Example 3 Protective effect of Chinese medicine composition on collagen-induced arthritis mice

[0067] 1. Experimental Materials

[0068] 1.1 Animals

[0069] 60 C57BL / 6 mice, SPF grade, male, 8 weeks old.

[0070] Breeding environment: room temperature 20-26℃, relative humidity controlled at 40-70%, 5 birds per cage.

[0071] 1.2 Medication

[0072] Chinese medicine composition, intermediate prepared according to the method of Example 1, Jiangsu Kangyuan Pharmaceutical Co., Ltd.; Tripterygium wilfordii polyglycosides tablets, Shanghai Fudan Fuhua Pharmaceutical Co., Ltd., batch number: 211002.

[0073] 1.3 Reagents

[0074] Chicken type II collagen, Chondrex, USA, batch number: 20012; complete Freund's adjuvant, Chondrex, USA, batch number: 7001.

[0075] 1.4 Instruments

[0076] Electronic balance, Mettler-Toledo, Switzerland, model: ME104E; toe volume measuring instrument, Anhui Zhenghua Biological Instrument Equipment Co., Ltd., model: ZH-LUO-G7.

[0077] 2. Dosage design

[0078] Based on the adult clinical dose of 96g of crude drug per day, the equivalent dose for mice, calculated using the body surface area method, is 18.0g / kg. Using a 1 / 4:1 / 2:1 dosing regimen, the low dose of the Chinese medicine composition is 4.5mg / kg, and the medium dose is 9.0g / kg.

[0079] The clinical daily dose of Tripterygium wilfordii glycosides tablets for humans is 1-1.5 mg / kg. Calculated based on 1.5 mg / kg, the equivalent dose for mice converted according to the body surface area method is 16.5 mg / kg.

[0080] 3. Experimental Methods

[0081] C57BL / 6 mice were adapted for one week with free access to feed and water. Ten mice in the normal control group were subcutaneously injected with 0.1 mL of normal saline at the base of their tails, while the remaining mice were subcutaneously injected with 0.1 mL of the modeling agent (bovine type II collagen solution (V): complete Freund's adjuvant (V) = 1:1) at the base of their tails. This injection constituted the first immunization. One week later, the second immunization was performed according to the initial immunization protocol. Successful modeling was determined by a joint index score (the sum of the scores for all four limbs) > ​​2. Successful modeling animals were randomly divided into a model control group, a tripterygium wilfordii polyglycosides group, and low-, medium-, and high-dose groups of the traditional Chinese medicine composition, with 10 mice in each group. Each group was administered the corresponding drug by oral gavage at a volume of 10 mL / kg once daily for 21 consecutive days. The normal and model control groups were also administered distilled water under the same conditions.

[0082] Before establishing the arthritis mouse model, the swelling thickness of the right hind paw was measured using a toe volume meter and the arthritis index score was performed. The scoring criteria are shown in Table 1. The paw swelling value and arthritis index score were measured every 7 days after administration.

[0083] 4. Statistical methods

[0084] The results were statistically analyzed using t-test.

[0085] 5. Experimental Results

[0086] 5.1 Effect on the Arthritis Index Score of Rheumatoid Arthritis Model Mice

[0087] After the modeling agent was injected into the tail vein of mice, the arthritis index score of the mice was significantly increased compared with the normal control group, with statistically significant differences (P<0.01); after 21 days of continuous administration, the arthritis index scores of the low, medium and high dose groups of the Chinese medicine composition were significantly reduced compared with the model control group at each time point (P<0.01), as shown in Table 5 for details.

[0088] Table 5: Effects on arthritis index scores in rheumatoid arthritis model mice

[0089]

[0090] Note: Compared with the normal control group, ## P<0.01; compared with the model control group, **P<0.01.

[0091] 5.2 Effects on foot swelling in rheumatoid arthritis model mice

[0092] After the modeling agent was injected into the tail vein of mice, the paw swelling values ​​of the mice were significantly increased compared with the normal control group, with statistically significant differences (P<0.01); after 21 days of continuous administration, the paw swelling values ​​of the low, medium and high dose groups of the Chinese medicine composition were significantly reduced compared with the model control group at each time point (P<0.01), as shown in Table 6 for details.

[0093] Table 6: Effects on foot swelling in rheumatoid arthritis model mice

[0094]

[0095] Note: Compared with the normal control group, ## P<0.01; compared with the model control group, **P<0.01.

[0096] 6. Experimental Conclusion

[0097] The Chinese medicine composition at doses of 4.5, 9.0 and 18 g crude drug / kg can significantly inhibit the arthritis index score of rheumatoid arthritis model mice, and significantly reduce the foot swelling of the model mice, suggesting that the Chinese medicine composition has a certain therapeutic effect on rheumatoid arthritis.

[0098] The above embodiments of the present invention are merely examples for the purpose of clearly illustrating the present invention, and are not intended to limit the embodiments of the present invention. Those skilled in the art will appreciate that other variations or modifications may be made based on the above description. It is not necessary and impossible to enumerate all embodiments here. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present invention shall be included within the scope of protection of the claims of the present invention.

Claims

1. Use of a Chinese medicine composition in the preparation of a medicine for rheumatoid arthritis, characterized in that: The traditional Chinese medicine composition is prepared from the following components: 5-15 parts of dried ginger, 15-25 parts of astragalus root, 5-15 parts of salt Morinda officinalis, 5-15 parts of Dictamnus dahurica, 25-35 parts of calcined oyster shell, 5-10 parts of Schisandra chinensis, and 5-15 parts of Saposhnikovia divaricata.

2. The use according to claim 1, characterized in that The traditional Chinese medicine composition is prepared from the following components by weight: 9-11 parts of dried ginger, 19-23 parts of astragalus, 9-11 parts of salt Morinda officinalis, 9-11 parts of Dictamni cortex, 28-34 parts of calcined oyster shell, 6-7 parts of Schisandra chinensis, and 9-11 parts of Saposhnikovia divaricata.

3. The use according to claim 1, characterized in that The traditional Chinese medicine composition is prepared from the following components by weight: 10 parts of dried ginger, 20 parts of astragalus, 10 parts of salt Morinda officinalis, 10 parts of Dictamnus dasycarpus, 30 parts of calcined oyster shell, 6 parts of Schisandra chinensis, and 10 parts of Saposhnikovia divaricata.

4. The use according to any one of claims 1 to 3, characterized in that: The preparation method of the traditional Chinese medicine composition comprises the following steps: taking dried ginger, salt morinda root, astragalus root, white mulberry bark, calcined oyster shell, schisandra chinensis and saposhnikovia root, adding 10 times the amount of water, decocting twice, each time for 1 hour, filtering, combining the filtrate, concentrating to a clear paste with a relative density of 1.07-1.15 (60°C), spray drying, and obtaining a dry paste powder.

5. The use according to claims 1-3, characterized in that The drug includes pharmaceutically acceptable excipients or additives.

6. The use according to claim 5, characterized in that The pharmaceutically acceptable excipients or additives include fillers, disintegrants, lubricants, suspending agents, binders, sweeteners, flavoring agents, preservatives, and bases.

7. The use according to any one of claims 1 to 3, characterized in that: The dosage form of the medicine is granules, tablets or capsules.

8. The use according to any one of claims 1 to 3, characterized in that: The preparation method of the medicine comprises: Take 10kg of dried ginger, 10kg of salt Morinda officinalis, 20kg of Astragalus membranaceus, 10kg of Dictamnus cortex, 30kg of calcined oyster shell, 6kg of Schisandra chinensis and 10kg of Saposhnikovia divaricata, add 10 times the amount of water, decoct twice, each time for 1 hour, filter, combine the filtrate, concentrate to a clear paste with a relative density of 1.07-1.15 (60°C), spray dry to obtain a Chinese medicine composition intermediate, add dextrin, mix well, granulate with 90% ethanol, dry, and granulate to obtain the product.

9. Use of a Chinese medicine composition in the preparation of a medicament for treating or preventing inflammation caused by rheumatoid arthritis, characterized in that: The traditional Chinese medicine composition is prepared from the following components: 5-15 parts of dried ginger, 15-25 parts of astragalus root, 5-15 parts of salt Morinda officinalis, 5-15 parts of Dictamnus dahurica, 25-35 parts of calcined oyster shell, 5-10 parts of Schisandra chinensis, and 5-15 parts of Saposhnikovia divaricata.

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