A traditional Chinese medicine composition for treating rheumatoid arthritis and its application

Abstract

This invention relates to the field of traditional Chinese medicine (TCM) technology, specifically to a TCM composition for treating rheumatoid arthritis and its application. The TCM composition comprises the following raw materials: mulberry twigs, Gentiana macrophylla, Phellodendron chinense, earthworm, stir-fried Arctium lappa, Achyranthes bidentata, stir-fried Bombyx mori, Lonicera japonica, and Spatholobus suberectus. This TCM composition can reduce arthritis scores and paw volume in rats with rheumatoid arthritis, reduce the spleen coefficient in rats with rheumatoid arthritis, significantly reduce TNF-α, IL-6, and IL-1β in rat serum, improve joint inflammation, and has no toxic side effects. This indicates that the TCM composition for treating rheumatoid arthritis in this application can alleviate symptoms in patients with rheumatoid arthritis, exert its anti-inflammatory and analgesic effects, and thus treat rheumatoid arthritis.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of traditional Chinese medicine, and particularly relates to a traditional Chinese medicine composition for treating rheumatoid arthritis and application thereof. BACKGROUND

[0002] Rheumatoid arthritis (RA) is an autoimmune disease with synovitis as the pathological basis and eventually leading to joint deformity. Its etiology is still in the exploratory stage, but studies have shown that it may be closely related to factors such as autoimmunity, heredity and microbial infection. The global prevalence rate is 0.2% to 1.0%, and in China, the prevalence rate is 0.28% to 0.41%, with a cumulative patient population of nearly 5 million. The male-to-female ratio of the disease is about 1:4, and most patients are female, with an onset age of 20 to 55 years. Rheumatoid arthritis is recurrent, with morning stiffness, joint swelling and other symptoms during the onset period, and there are abnormal conditions of erythrocyte sedimentation rate (ESR), rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (CCP). Due to the long course of RA, patients not only face long-term physical discomfort, but also cause psychological and life distress, making patients prone to negative emotions, reducing the quality of life, and even damaging joint function.

[0003] Currently, the western medicine treatment of rheumatoid arthritis is roughly divided into four categories: (1) Non-steroidal anti-inflammatory analgesics (NSAIDs) are the first choice for treating RA, and their main role is to alleviate symptoms and improve joint function, but they do not slow down the progression of the disease and cannot prevent joint damage. In addition, the incidence of gastric ulcers in long-term NSAIDs users is about 12% to 30%, so the use of this type of drug is limited in clinical practice. (2) Disease-modifying antirheumatic drugs (DMARDs) are drugs that can effectively prevent joint imaging damage in RA patients. DMARDs have a slow onset and need to be taken for several weeks or months to significantly control inflammation, prevent or slow down joint damage, and thus control or delay the progression of RA. (3) Glucocorticoids (GC) can inhibit cell-mediated immune responses and have a rapid onset, which can control acute phase lesions and delay RA early joint damage and improve joint function. GC is often used in combination with DMARDs drugs, although GC treatment of RA is effective, but it has many adverse reactions and will relapse after discontinuation. (4) Biological agents were introduced in 1996 and are a popular topic in recent years of domestic and foreign research. Studies have shown that biological therapy can effectively improve the pain, swelling and stiffness of RA patients and joint deformity. The remission rate of biological agents for RA disease activity is as high as 50%. In general, anti-tumor necrosis factor combined with DMARDs is recommended for joint use. However, biological therapy has greater side effects, long-term administration can damage liver and kidney function and the digestive system, and is also expensive, which most patients cannot afford.

[0004] Rheumatoid arthritis is a chronic inflammatory disease requiring long-term treatment. Therefore, finding a long-term effective therapy with minimal side effects is crucial, making traditional Chinese medicine a key area of ​​research. For example, invention patent CN117427140A discloses a traditional Chinese medicine composition for treating rheumatoid arthritis pain and its application. This composition comprises the following raw materials in parts by weight: 10-25 parts cinnamon twig, 10-25 parts white peony root, 5-25 parts licorice root, 10-30 parts fresh ginger, 15-30 parts jujube, 10-30 parts ginseng, 10-30 parts angelica root, 10-30 parts morinda root, and 10-30 parts ophiopogon root. This traditional Chinese medicine composition can effectively improve the pain level, alleviate joint pain, and reduce joint mobility in patients with rheumatoid arthritis. Chinese patent CN114558075B discloses a traditional Chinese medicine composition for treating rheumatoid arthritis, its preparation method, and its application. The composition uses Achyranthes bidentata and Dioscorea nipponica as the principal herbs, and is complemented by Sinomenium acutum, Piper kadsura, Cinnamomum cassia, Eucommia ulmoides, Acanthopanax senticosus, Acer rubrum, and Homalomena occulta. This traditional Chinese medicine composition can effectively reduce the secretion of inflammatory factors, interleukin-6 (IL-6), and interleukin-1β (IL-1β) in the supernatant of synovial fibroblasts (MH7A) cells induced by tumor necrosis factor-α (TNF-α). Simultaneously, it can effectively upregulate the expression of pro-apoptotic protein (Bax) / anti-apoptotic protein (Bcl-2), thereby promoting MH7A cell apoptosis and exhibiting a good therapeutic effect on rheumatoid arthritis.

[0005] The inventor's research group has long been committed to the research of traditional Chinese medicine treatment for rheumatoid arthritis. In view of the current situation that rheumatoid arthritis patients need to take medication for a long time, they unexpectedly obtained a traditional Chinese medicine composition for the treatment of rheumatoid arthritis. The traditional Chinese medicine composition can reduce the arthritis score and paw volume of rheumatoid arthritis rats, reduce the spleen coefficient of rheumatoid arthritis rats, significantly reduce TNF-α, IL-6 and IL-1β in rat serum, improve the inflammatory response of joints, and has no toxic side effects. Summary of the Invention

[0006] The primary objective of this invention is to provide a traditional Chinese medicine composition for treating rheumatoid arthritis, the composition comprising the following raw materials: mulberry twigs, Gentiana macrophylla, Phellodendron chinense, earthworm, stir-fried Arctium lappa, Achyranthes bidentata, stir-fried Bombyx mori, Lonicera japonica, and Spatholobus suberectus.

[0007] Preferably, the traditional Chinese medicine composition comprises the following raw materials in parts by weight: 12 parts of mulberry twig, 12 parts of gentian root, 12 parts of phellodendron bark, 12 parts of earthworm, 12 parts of stir-fried burdock fruit, 12 parts of achyranthes root, 12 parts of stir-fried silkworm pupae, 20 parts of honeysuckle vine, and 20 parts of chicken blood vine.

[0008] Preferably, the traditional Chinese medicine composition is composed of the following raw medicinal materials in parts by weight: 12 parts of mulberry branches, 12 parts of gentian macrophyllas, 12 parts of phellodendron amurense, 12 parts of earthworms, 12 parts of stir-fried arctium lappa, 12 parts of achyranthes bidentata, 12 parts of stir-fried bombyx batryticatus with bran, 20 parts of honeysuckle vines, and 20 parts of suberect spatholobus.

[0009] Preferably, pharmaceutically acceptable excipients are added to prepare an oral preparation or an injection preparation.

[0010] Preferably, the oral preparation includes tablets, capsules, granules, pills, syrup, oral solutions, oral suspensions or oral emulsions.

[0011] Preferably, the injection preparation includes injection solutions or powder injections.

[0012] The second object of the present invention is to provide a drug including the traditional Chinese medicine composition.

[0013] The third object of the present invention is to provide the use of the traditional Chinese medicine composition in the preparation of drugs for preventing and treating rheumatoid arthritis.

[0014] The beneficial effects of the present invention are as follows: The present invention provides a traditional Chinese medicine composition for treating rheumatoid arthritis. The traditional Chinese medicine composition can reduce the arthritis score and toe volume of rats with rheumatoid arthritis, reduce the spleen coefficient of rats with rheumatoid arthritis, significantly reduce TNF-α, IL-6, and IL-1β in the serum of rats, improve the joint inflammatory reaction of the body, and has no toxic and side effects.

[0015] Guided by the traditional Chinese medicine theory of "clearing heat and removing dampness, dredging collaterals and relieving pain", the mulberry branches in the formula are of neutral nature, dispelling wind-dampness and being good at reaching the meridians of the limbs, dredging and facilitating joints; the honeysuckle vines clear heat, dispel wind and dredge collaterals to relieve pain; the gentian macrophyllas are of cold nature, dispelling wind-dampness, clearing damp-heat and dredging collaterals to relieve pain. The three herbs are combined as the monarch drugs to dispel wind-dampness and dredge collaterals to relieve pain. The earthworms are used as the minister drugs to clear heat and dredge collaterals to relieve pain, and the phellodendron amurense clears heat and dries dampness. The monarch and minister herbs are combined to enhance the effects of dispelling wind-dampness and dredging collaterals to relieve pain. The suberect spatholobus is used as the assistant drug to activate blood circulation and enrich blood, and relax tendons and activate collaterals; the arctium lappa clears heat and detoxifies, reduces swelling and relieves pain, so as to dispel wind-dampness without consuming yin and blood, nourish yin and blood without hindering pathogens, meaning tonifying while dispersing and dispersing while tonifying. The achyranthes bidentata tonifies the liver and kidney and promotes blood circulation to remove stasis, and the stir-fried bombyx batryticatus with bran activates blood circulation to remove stasis, dredges collaterals to relieve pain and also serves as the guiding drug to lead the other drugs downward. The whole formula is based on the pathogenesis and clinical characteristics of "damp-heat accumulation and meridian obstruction", and together achieves the effects of "clearing heat and removing dampness, dredging collaterals and relieving pain". The monarch and minister herbs of the traditional Chinese medicine composition of Qingre Tongbi Pills are appropriate, and the proportion is reasonable, which can significantly improve the arthritis symptoms of rats, significantly reduce the serum inflammatory factors, and significantly improve the joint swelling degree. Applying the traditional Chinese medicine composition to clinical patients, the traditional Chinese medicine clinical symptoms of the patients are significantly improved, and the quality of life scores are significantly higher than those before treatment. The traditional Chinese medicine composition of the present invention has broad application prospects. Detailed implementation manners

[0016] The technical solution of the present invention will be clearly and completely described below with reference to the embodiments. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0017] Unless otherwise specified, all drugs or reagents used in the following examples are commercially available.

[0018] The experimental methods used in the following examples are all conventional methods.

[0019] Example 1: Treatment of Rheumatoid Arthritis with a Traditional Chinese Medicine Composition

[0020] 1. Experimental Procedure

[0021] 1.1 Establishment and grouping of a rat model of rheumatoid arthritis

[0022] Eighty 8-week-old SD rats, half male and half female, were purchased from the Lanzhou Veterinary Research Institute of the Chinese Academy of Agricultural Sciences and housed there. After one week of acclimatization, ten SD rats were randomly selected as a blank control group (normal group N=10) using a random number table. The remaining 70 rats were used to establish a rat model of rheumatoid arthritis by injecting an emulsion of collagen II and Freund's incomplete adjuvant 2-3 cm from the base of the tail. After successful modeling, the rats were randomly divided according to body weight using a random number table method with Excel software: ① Model group (N=10); ② High-dose Qingre Tongbi Pill group (N=10); ③ Medium-dose Qingre Tongbi Pill group (N=10); ④ Low-dose Qingre Tongbi Pill group (N=10); ⑤ Control group 1 (N=10); ⑥ Control group 2 (N=10). The dosage of Qingre Tongbi Pills was calculated based on the body surface coefficient of humans and rats in "Methodology of Pharmacological Research of Traditional Chinese Medicine". The dosage for the low-dose group was 0.6075 g / kg, the dosage for the medium-dose group was 1.215 g / kg, and the dosage for the high-dose group was 2.43 g / kg. The blank control group and the model group rats were administered the same volume of distilled water by gavage. Control group 1: 12 parts of mulberry twig, 12 parts of gentian root, 12 parts of phellodendron bark, 12 parts of earthworm, 12 parts of achyranthes root, 12 parts of stir-fried silkworm, 20 parts of honeysuckle vine, and 20 parts of chicken blood vine, with a dosage of 1.85 g / kg. Control group 2: 0.39 g / kg of stir-fried burdock seed. The rats in each group were administered the pills by gavage for 4 weeks.

[0023] 1.2 Observation Indicators and Measurement Methods

[0024] (1) General observation of rats: The hair, diet, water intake, excretion and other conditions of rats in each group were observed and recorded every day, and the weight of rats was recorded every week during the experiment.

[0025] (2) The arthritis index was used to score the arthritis of each rat. The scoring criteria were as follows: no redness or swelling = 0 points, redness but no swelling in the toe joints = 1 point, mild redness and swelling in the toe joints = 2 points, moderate redness and swelling in the toe joints = 3 points, and severe redness and swelling in the toe joints with limited mobility = 4 points. The degree of swelling and mobility of the four paws of the rats were observed and the scores were recorded each time. A toe volume measuring instrument was also used to measure and record the volume of the two hind paws of the rats.

[0026] (3) Body weight and organ index analysis: After the drug intervention, the rats were weighed, and their livers and spleens were removed. The connective tissue around the organs was cleaned and weighed immediately. The organ index (%) was calculated using the following formula: Organ index (%) = Organ weight (mg) / Body weight (g) × 100%.

[0027] (4) Hematological index detection: After the drug intervention, blood was collected after anesthesia with sodium pentobarbital injection. After blood collection, the supernatant was collected after centrifugation at 3000 rpm for 10 min. The serum levels of tumor necrosis factor α (TNFalpha, TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) were detected by ELISA.

[0028] 2. Experimental Results

[0029] 2.1 Observation of the general condition of rats

[0030] As shown in Table 1, there was no statistically significant difference in the body weight of rats in each group before modeling.

[0031] Table 1. Body weight of rats in different groups

[0032]

[0033] 2.2 Arthritis score and paw volume in rats

[0034] As shown in Tables 2 and 3, compared with the blank control group, the arthritis score and toe volume of rats in the model group were significantly increased (P < 0.01); compared with the model group, the arthritis score and toe volume of rats in the medium and high dose groups of traditional Chinese medicine were significantly decreased, with the high dose group showing the most significant effect, and the difference was statistically significant (P < 0.01). Compared with the model group, there were differences in the low dose group of traditional Chinese medicine and control group 1 (P < 0.05). Compared with the model group, there was no statistically significant difference in control group 2 (P > 0.05).

[0035] Table 2. Changes in arthritis scores in rats of different groups.

[0036]

[0037]

[0038] Table 3. Changes in paw volume in rats of different groups

[0039]

[0040] 2.3 Liver and spleen indices in rats

[0041] As shown in Table 4, there was no liver organ coefficient, and there was no statistically significant difference among the groups (P>0.05).

[0042] Table 4 Liver index of rats in different groups

[0043]

[0044] As shown in Table 5, compared with the blank control group, the spleen coefficient of rats in the model group was significantly increased (P < 0.01); compared with the model group, the spleen coefficient of rats in the medium and high dose groups of traditional Chinese medicine was significantly decreased, with the high dose group showing the most significant effect, and the difference was statistically significant (P < 0.01). Compared with the model group, there were differences in the low dose group of traditional Chinese medicine and control group 1 (P < 0.05). Compared with the model group, there was no statistically significant difference in control group 2 (P > 0.05).

[0045] Table 5 Spleen index of rats in different groups

[0046]

[0047] 2.4 Hematological parameters of rats

[0048] As shown in Tables 6-8, compared with the blank control group, the serum levels of tumor necrosis factor α (TNFalpha), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in the model group rats were significantly increased (P < 0.01). Compared with the model group, the serum levels of TNF-α, IL-6, and IL-1β in the medium- and high-dose groups of the traditional Chinese medicine were significantly decreased, with the high-dose group showing the most significant effect (P < 0.01). Compared with the model group, the low-dose group of the traditional Chinese medicine and control group 1 showed significant differences (P < 0.05). Compared with the model group, control group 2 showed no significant difference (P > 0.05).

[0049] Table 6. Changes in TNF-α in rats of different groups.

[0050]

[0051] Table 7. Changes in IL-6 levels in rats of different groups.

[0052]

[0053] Table 8. Changes in IL-β levels in rats of different groups based on body weight.

[0054]

[0055] In summary, this invention provides a traditional Chinese medicine composition for treating rheumatoid arthritis. This composition can treat rheumatoid arthritis in rats, reducing arthritis scores and paw volume, decreasing spleen coefficient, and significantly lowering serum TNF-α, IL-6, and IL-1β levels, thus improving the body's joint inflammation response without toxic side effects. This demonstrates that the traditional Chinese medicine composition for treating rheumatoid arthritis in this application can alleviate symptoms in patients with rheumatoid arthritis, exerting anti-inflammatory and analgesic effects, thereby treating rheumatoid arthritis.

Claims

1. A traditional Chinese medicine composition for treating rheumatoid arthritis, characterized in that, The traditional Chinese medicine composition is composed of the following raw materials by weight: mulberry branch 12 parts, gentiana 12 parts, Chinese goldthread root 12 parts, earthworm 12 parts, fried burdock seed 12 parts, chaff fried silkworm 12 parts, chaff fried silkworm 12 parts, chaff fried silkworm 12 parts, chaff fried silkworm 12 parts, chaff fried silkworm 12 parts, chaff fried silkworm 12 parts, chaff fried silkworm 12 parts, chaff fried silkworm 12 parts, chaff fried silkworm 12 parts, chaff fried silkworm 12 parts, chaff fried silkworm 12 parts, chaff fried silkworm 12 parts, chaff fried silkworm 12 parts, chaff fried silkworm 12 parts, chaff fried silkworm 12 parts, chaff fried silkworm 12 parts, chaff fried silkworm 12 parts, chaff fried silkworm 12 parts, chaff fried silkworm 12 parts, chaff fried silkworm 12 parts, chaff fried silkworm 12 parts, chaff fried silkworm 12 parts, chaff fried silkworm 12 parts, chaff fried silkworm 12 parts, chaff fried silkworm 12 parts, chaff fried silkworm 12 parts, chaff fried silkworm 12 parts, chaff fried silkworm 12 parts, chaff fried silkworm 12 parts, chaff fried silkworm 12 parts, chaff fried silkworm 12 parts, chaff fried silkworm 12 parts, chaff fried silkworm 12 parts, chaff fried silkworm 12 parts, chaff fried silkworm 12 parts, chaff fried silkworm 12 parts, chaff fried silkworm 12 parts, chaff fried silkworm 2. The traditional Chinese medicine composition of claim 1, wherein, ​ 3. The traditional Chinese medicine composition of claim 2, wherein, ​ 4. The traditional Chinese medicine composition of claim 2, wherein, ​ 5. A medicament for treating rheumatoid arthritis, characterized by comprising a compound of the formula (I) or a pharmaceutically acceptable salt thereof. ​ ​

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