Pharmaceutical composition for treating gouty arthritis, preparation method and application thereof

Abstract

The present invention relates to the technical field of Chinese medicine and preparation method for treating gouty arthritis, a pharmaceutical composition for treating gouty arthritis and its preparation method and application, the pharmaceutical composition, the medicinal materials include aconite, fenugreek, cassia twig, Poria, Rhizoma Smilacis Glabrae, Caulis Trachelospermi and Codonopsis Pilosula of specific compatibility, and the pharmaceutical composition is prepared by reflux decoction. The pharmaceutical composition of the present invention has a precise compatibility of each medicinal flavor, and plays a synergistic effect together, has the effects of warming yang and removing dampness, promoting qi, unblocking channels, reducing swelling, dispersing knots and relieving pain, and for gout cold-damp syndrome, can treat cold-damp accumulation, qi stagnation and blood stasis syndromes, tendon and bone pain, hand and foot paralysis and pain, foot and knee swelling and pain, qi stagnation and blood stasis, nodule swelling and pain, nodule immobility, etc., has a good therapeutic effect on cold-dampness arthritis, and the recurrence rate is low. At the same time, the pharmaceutical composition of the present invention has few raw materials, is easy to prepare, convenient to use, has a definite efficacy, stable medicinal properties, and good patient compliance, and has a good application prospect.

Description

Technical Field

[0001] The invention relates to the technical field of traditional Chinese medicine for treating gouty arthritis and preparation method thereof, and is a pharmaceutical composition for treating gouty arthritis and a preparation method thereof, as well as application of the pharmaceutical composition in preparing a medicine for treating gouty arthritis. Background Art

[0002] Gout arthritis generally refers to gouty arthritis, which is a metabolic disease mainly caused by joint inflammation caused by urate crystals due to long-term accumulation of uric acid, and is characterized by joint pain, swelling and limited movement. In recent years, with the improvement of living standards and changes in dietary structure, the prevalence of hyperuricemia and gout has increased year by year, with a clear trend of younger age. The cold climate, long winter and large temperature difference between day and night in Xinjiang may cause the first onset of gout patients to be more complex. Studies have shown that the average age of onset of gout patients in Xinjiang is 42.95 years old, which is lower than the national level of 44.8 years old. This may be closely related to the living and eating habits of young people in Xinjiang and climatic factors. Gout patients are often accompanied by one or more complications, common complications include hypertension, hyperlipidemia, diabetes, obesity, arteriosclerosis, coronary heart disease, cerebrovascular disease, etc. As the metabolic disorder in patients with gouty arthritis intensifies, the risk of cardiovascular disease and ischemic stroke may be increased. Therefore, the diagnosis and treatment of gouty arthritis has received more and more attention.

[0003] At present, the three types of drugs commonly used internationally for lowering uric acid are: allopurinol or febuxostat that inhibit uric acid synthesis, benzbromarone or probenecid that promote uric acid excretion, and recombinant urate oxidase that decomposes uric acid. From the perspective of clinical application, these three types of drugs have their own advantages and disadvantages in clinical application.

[0004] Allopurinol is a xanthine oxidase inhibitor that can reduce the synthesis of uric acid from hypoxanthine and xanthine by inhibiting the activity of xanthine oxidase, thereby reducing blood uric acid levels. It has been used for a long time in clinical practice, but it has many side effects, often with impaired liver and kidney function and decreased leukocytes, especially causing severe hypersensitivity reactions in patients with positive HLA-B*5801 alleles. Febuxostat is also a xanthine oxidase inhibitor that can effectively reduce the synthesis of uric acid. However, since 2018, studies have reported that febuxostat can cause adverse cardiovascular events in elderly patients. Therefore, the "2020 American ACR Gout Management Guidelines" propose that for gout patients with a history of cardiovascular disease or new cardiovascular events, it is recommended to selectively change febuxostat to other alternative uric acid-lowering drugs.

[0005] Benzbromarone is a derivative of benzofuran, which has a strong deuricating effect. Studies have found that it can also effectively inhibit the production of uric acid, and has a dual effect on reducing the concentration of uric acid in the blood. At present, benzbromarone is recognized in my country, but because of its hepatotoxicity, especially in patients with kidney stones and / or renal insufficiency, its application is restricted, and its application in Europe and the United States is significantly restricted. Probenecid, also a drug that accelerates uric acid excretion, has been used clinically as early as 1950, but due to too many drug interactions and strong hepatotoxicity and renal toxicity, it has now been eliminated.

[0006] Recombinant uricase is an exogenously supplemented uricase oxidase that can rapidly oxidize uric acid, thereby accelerating the process of lowering uric acid and accelerating the dissolution of tophi, thereby effectively controlling gout attacks. With the development of biotechnology, uricase has been approved for marketing as a biological agent for decomposing uric acid, such as Prekysit. However, clinical studies have found that this treatment regimen causes fever, allergies, and high rejection, and is prone to induce systemic urticaria-like allergic reactions. In addition, the drug is expensive, which to a certain extent limits the widespread clinical application of Prekysit. Therefore, there is an urgent need to develop a drug that can effectively relieve gouty arthritis.

[0007] In traditional Chinese medicine theory, gouty arthritis belongs to the category of "arthralgia", "limb arthralgia" and "limb arthralgia". It is a combination of deficiency and excess, but it is often a mixture of deficiency and excess. The attack is mainly manifested in the joints and the pain of the soft tissues around the joints. The attack has both bone pain and muscle pain. Traditional Chinese medicine treatment can adopt personalized treatment according to the overall condition of the patient, which has obvious advantages over the symptomatic treatment of Western medicine. In clinical treatment of gout, traditional Chinese medicine can not only reduce the adverse reactions caused by Western medicine through methods such as dialectical treatment and staged treatment, but also has a significant effect in reducing the recurrence rate. Patent CN103239654B discloses a drug for treating acute gouty arthritis, but the drug is complex, involving more than 30 raw materials, which is not easy to prepare. Therefore, it is urgent to study a drug combination for treating gouty arthritis with simple raw materials, easy preparation and use, excellent efficacy, definite efficacy, stable drug properties and low adverse reaction rate. Summary of the invention

[0008] The present invention provides a pharmaceutical composition for treating gouty arthritis, a preparation method and application thereof, which overcomes the deficiencies of the above-mentioned prior art and can effectively solve the problem that the existing drugs for treating gouty arthritis have complex formulations and are inconvenient to prepare.

[0009] One of the technical solutions of the present invention is achieved through the following measures: a pharmaceutical composition for treating gouty arthritis, comprising 9 to 20 parts of aconite, 10 to 40 parts of fenugreek, 10 to 40 parts of cassia twig, 10 to 40 parts of poria, 10 to 40 parts of smilax glabra, 10 to 40 parts of trachelospermum officinale, and 5 to 20 parts of codonopsis pilosula, in terms of weight proportions.

[0010] The following is a further optimization and / or improvement of one of the above-mentioned technical solutions:

[0011] Preferably, the pharmaceutical composition for treating gouty arthritis comprises, by weight, 9 parts of aconite root, 40 parts of fenugreek, 40 parts of cinnamon twig, 12 parts of poria, 40 parts of smilax glabra, 40 parts of trachelospermum officinale, and 5 parts of codonopsis pilosula.

[0012] Preferably, the pharmaceutical composition for treating gouty arthritis comprises, by weight, 12 parts of aconite root, 25 parts of fenugreek, 32 parts of cinnamon twig, 32 parts of poria, 25 parts of smilax glabra, 30 parts of trachelospermum officinale, and 10 parts of codonopsis pilosula.

[0013] Preferably, the pharmaceutical composition for treating gouty arthritis comprises, by weight, 20 parts of aconite root, 12 parts of fenugreek, 12 parts of cinnamon twig, 40 parts of Poria cocos, 10 parts of Smilax glabra, 10 parts of Trachelospermum officinale, and 15 parts of Codonopsis pilosula.

[0014] The above-mentioned pharmaceutical composition for treating gouty arthritis is prepared according to the following method:

[0015] The medicinal materials are prepared in required amounts, and water whose volume is 5 to 8 times that of the medicinal materials is added to the medicinal materials to obtain the medicine to be decocted; the medicine to be decocted is then decocted, and after the decocting is completed, the medicinal liquid is cooled and filtered to obtain a filtered soup; the filtered soup is concentrated to obtain a concentrated soup; the concentrated soup is dried to obtain a freeze-dried Chinese medicine powder, that is, a pharmaceutical composition for treating gouty arthritis.

[0016] The prepared medicinal materials are first added with water having a volume multiple of 2.5 to 4 times that of the medicinal materials for soaking for 3 to 4 hours, and the soaked medicinal materials are added with a required amount of water to obtain the decocted medicine.

[0017] The above decoction method adopts the reflux decoction method, and the decoction time is 2 hours to 2.5 hours; the volume multiple of the concentrated soup is one fifteenth to one tenth of the medicine to be decocted.

[0018] The mass ratio of the above-mentioned Chinese medicine freeze-dried powder to the medicinal materials is 0.1 to 0.2:1.

[0019] The freeze-drying temperature is -40°C and the freezing time is 20h to 24h.

[0020] In the present invention, Fenugreek (Latin name: Trigonella foenum-graecum L.), is the common name of the plant Fenugreek of the genus Fenugreek of the Leguminosae family, also known as fenugreek, which is a Xinjiang authentic medicinal material. The dried mature seeds of fenugreek are included in the "Pharmacopoeia of the People's Republic of China" as a commonly used Chinese medicine, and belong to the variety of medicine and food. Fenugreek is warm in nature, good at replenishing kidney yang, dispersing cold and dampness, promoting qi, and stopping diarrhea. It can treat lung diseases, cold pain in the waist and knees, cold pain in the lower abdomen, kidney deficiency spermatorrhea and impotence. Modern research has found that fenugreek can help digestion, treat bronchitis, lower blood sugar and blood lipids, protect against cerebral ischemia, improve learning and memory disorders, treat skin diseases and treat and hyposexuality. However, there is no report on the research of Chinese medicine prescriptions featuring fenugreek in the treatment of gouty arthritis. The feature of the present invention is that fenugreek and aconite are both monarch drugs, which can effectively relieve gouty arthritis.

[0021] This prescription is used to treat cold-dampness arthritis, warm the meridians and dispel cold, dispel wind and relieve pain as the main treatment principle. In the prescription, aconite and fenugreek are the main ingredients, which can support yang, dispel cold and remove dampness; cinnamon twig is used as the auxiliary ingredient to warm the meridians, dispel cold and relieve the symptoms; tuckahoe, smilax glabra and clematis are used as the auxiliary ingredients to dispel wind and dredge the meridians, and unblock the joints; and codonopsis is used to promote qi circulation and assist in removing blood stasis and unblocking the joints.

[0022] The second technical solution of the present invention is achieved by the following measures: The preparation method of the pharmaceutical composition for treating gouty arthritis described in one of the technical solutions is carried out as follows:

[0023] The medicinal materials are prepared in required amounts, and water whose volume is 5 to 8 times that of the medicinal materials is added to the medicinal materials to obtain the medicine to be decocted; the medicine to be decocted is then decocted, and after the decocting is completed, the medicinal liquid is cooled and filtered to obtain a filtered soup; the filtered soup is concentrated to obtain a concentrated soup; the concentrated soup is dried to obtain a freeze-dried Chinese medicine powder, that is, a pharmaceutical composition for treating gouty arthritis.

[0024] The following is a further optimization and / or improvement of the second technical solution of the above invention:

[0025] The prepared medicinal materials are first added with water having a volume multiple of 2.5 to 4 times that of the medicinal materials for soaking for 3 to 4 hours, and the soaked medicinal materials are added with a required amount of water to obtain the decocted medicine.

[0026] The above decoction method adopts the reflux decoction method, and the decoction time is 2 hours to 2.5 hours; the volume multiple of the concentrated soup is one fifteenth to one tenth of the medicine to be decocted.

[0027] The mass ratio of the above-mentioned Chinese medicine freeze-dried powder to the medicinal material is 0.1 to 0.2:1 (for example, 0.1:1, 0.2:1, etc.).

[0028] The freeze-drying temperature is -40°C and the freezing time is 20h to 24h.

[0029] The third technical solution of the present invention is achieved by the following measures: use of the pharmaceutical composition for treating gouty arthritis described in one of the technical solutions in the preparation of a drug for treating gouty arthritis.

[0030] The medicinal composition of the present invention is well matched with each other, and the synergistic effect is exerted together, and the effects of warming yang and removing dampness, promoting qi, unblocking collaterals, reducing swelling, dispersing nodules and relieving pain are achieved. For gout cold-damp syndrome, the cold-damp accumulation, various syndromes of qi stagnation and blood stasis, muscle and bone pain, hand and foot paralysis and pain, foot and knee swelling and pain, qi stagnation and blood stasis, nodule swelling and pain, nodule immobility, etc. can be treated, and the cold-dampness arthritis type gouty arthritis has a good therapeutic effect, and the recurrence rate is low. At the same time, the pharmaceutical composition of the present invention has few raw materials, is easy to prepare, convenient to use, has a definite curative effect, stable medicinal properties, good patient compliance, and has a good application prospect. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] Attached Figure 1 The results are for the serum uric acid content of rats in each group.

[0032] Attached Figure 2 The results of serum creatinine content of rats in each group.

[0033] Attached Figure 3 The results of serum urea nitrogen content of rats in each group.

[0034] Attached Figure 4 The results are for serum triglyceride content of rats in each group.

[0035] Attached Figure 5 The results are for the serum total cholesterol content of rats in each group.

[0036] Attached Figure 6 The results are for serum high density lipoprotein levels of rats in each group.

[0037] Attached Figure 7 The results of serum low-density lipoprotein levels in rats of each group.

[0038] Attached Figure 8 The left ankle joint swelling results of rats in each group.

[0039] Attached Fig. 9 The right ankle joint swelling results of rats in each group.

[0040] Attached Fig.10 Shown are the growth rates of the anterior-posterior diameter of the left ankle joint of rats in each group.

[0041] Attached Fig.11 The results of the growth rate of the anterior-posterior diameter of the right ankle joint of rats in each group.

[0042] Attached Fig.12 Shown are the growth rates of left paw thickness of rats in each group.

[0043] Attached Fig.13 Shown are the growth rates of right paw thickness of rats in each group.

[0044] Attached Fig.14 is the maximum climbing angle of rats in each group.

[0045] Attached Fig.15 The results of ankle joint morphological changes in rats in each group.

[0046] Fig.16 The results are for serum interleukin IL-1β content of rats in each group.

[0047] Figure 1-Figure 7 Compared with the control group: # P <0.05, ## P <0.01, ### P <0.001. Compared with the model group: * P <0.05; ** P <0.01; *** P <0.001.

[0048] Figure 8-Figure 9 Compared with the control group: # P <0.05, ## P <0.01, ### P <0.001. Compared with the model group: * P <0.05; ** P <0.01; *** P <0.001.

[0049] Figure 10-13 There was no statistical difference compared with the control group: ns. # P <0.05, ## P <0.01, ### P <0.001. Compared with the model group: * P <0.05; ** P <0.01; *** P <0.001.

[0050] Fig.14 Compared with the control group: # P <0.05, ## P <0.01, ### P <0.001. Compared with the model group: * P <0.05; ** P <0.01; *** P <0.001.

[0051] Fig.16 Compared with the control group: # P <0.05, ## P <0.01, ### P <0.001. Compared with the model group: * P <0.05; ** P <0.01; *** P <0.001. DETAILED DESCRIPTION

[0052] The present invention is not limited by the following embodiments, and specific implementation methods can be determined based on the technical solution of the present invention and actual conditions.

[0053] In the present invention, the Chinese medicine compound refers to a pharmaceutical composition for treating gouty arthritis.

[0054] The present invention will be further described below in conjunction with embodiments:

[0055] Embodiment 1: The Chinese medicine compound comprises 9g of aconite root, 40g of fenugreek, 40g of cinnamon twig, 12g of Poria cocos, 40g of Smilax glabra, 40g of Trachelospermum officinale, and 5g of Codonopsis pilosula.

[0056] Embodiment 2: The Chinese medicine compound comprises 12g of aconite root, 25g of fenugreek, 32g of cinnamon twig, 32g of Poria cocos, 25g of Smilax glabra, 30g of Trachelospermum officinale, and 10g of Codonopsis pilosula.

[0057] Example 3: The Chinese medicine compound comprises 20g of aconite root, 12g of fenugreek, 12g of cinnamon twig, 40g of Poria cocos, 10g of Smilax glabra, 10g of Trachelospermum officinale, and 15g of Codonopsis pilosula.

[0058] Example 4: The above-mentioned pharmaceutical composition for treating gouty arthritis can be prepared according to the following method:

[0059] The medicinal materials are prepared in required amounts, and water whose volume is 5 to 8 times that of the medicinal materials is added to the medicinal materials to obtain the medicine to be decocted; the medicine to be decocted is then decocted, and after the decocting is completed, the medicinal liquid is cooled and filtered to obtain a filtered soup; the filtered soup is concentrated to obtain a concentrated soup; the concentrated soup is dried to obtain a freeze-dried Chinese medicine powder, that is, a pharmaceutical composition for treating gouty arthritis.

[0060] Example 5: As an optimization of Example 4, the prepared medicinal materials are first added with water having a volume multiple of 2.5 to 4 times that of the medicinal materials for soaking for 3 to 4 hours, and the required amount of water is added to the soaked medicinal materials to obtain the decocted medicine.

[0061] Example 6: As an optimization of Example 4, the decoction method adopts the reflux decoction method, and the decoction time is 2 hours to 2.5 hours; the volume multiple of the concentrated soup is one fifteenth to one tenth of the medicine to be decocted.

[0062] Example 7: As an optimization of Example 4, the mass ratio of Chinese herbal lyophilized powder to medicinal materials is 0.1 to 0.2:1.

[0063] Example 8: As an optimization of Example 4, the freeze-drying temperature is -40°C and the freezing time is 20 to 24 hours.

[0064] Example 9: Use of the pharmaceutical composition for treating gouty arthritis in the preparation of a drug for treating gouty arthritis.

[0065] Study on the intervention of Guizhi Fuzi Decoction with different doses of aconite (i.e., a drug composition for treating gouty arthritis) on a rat model of cold-dampness gouty arthritis:

[0066] 1. Animal grouping and experimental procedure

[0067] 42 SD rats, male, weighing 190g to 210g, were purchased from the Animal Experiment Center of Xinjiang Medical University and kept in the SPF environment of the Animal Experiment Center of Xinjiang Medical University (London Approval Number: IACUC-20230321-10), with the room temperature maintained at 20±2°C and humidity at 50±2%. They were randomly divided into 6 groups, 7 in each group, namely the control group, model group, Example 1, Example 2, Example 3, and colchicine group. Each rat in the control group was fed 15g of conventional feed per day. For the model group, Example 1, Example 2, Example 3, and colchicine group, each rat in each group was fed 15g of high-fat and high-purine feed per day (purchased from Guangdong Medical Experiment Animal Center, processing number: 20230709). In addition, the ankle joints of each rat in the model group, Example 1, Example 2, Example 3 and colchicine group were immersed in an ice-water mixture for 15 minutes every day; each rat in Example 1, Example 2, Example 3 and colchicine group was given 2 mL of the corresponding drug for oral gavage treatment every day for 28 days. Starting from the 25th day, each rat in the control group was injected with 20 uL of sterile saline solution into the ankle joint; each rat in the model group, Example 1, Example 2, Example 3 and colchicine group was injected with 20 uL of sterile LPS solution into the ankle joint until the 28th day. Blood and tissue samples of animals were collected on the 28th day.

[0068] 2. Drug preparation and administration method

[0069] 2.1 Preparation and administration of the drugs of Example 1, Example 2 and Example 3:

[0070] All Chinese medicinal materials were purchased from Sichuan Guoqiang Chinese Medicine Pieces Co., Ltd., batch number: 220101. The dried drugs were configured in proportion and placed in a beaker, and 600 mL of distilled water was added to soak for 3 hours. After soaking, water was added to replenish the solution volume to 600 mL. The liquid and solid in the beaker were transferred to a round-bottom flask, heated to reflux for 2 hours, cooled, and filtered to obtain 600 mL of soup. The soup was concentrated to 100 mL under reduced pressure using a rotary evaporator (Gongyi Yuhua Instrument Co., Ltd. RE-2010), and freeze-dried using a freeze dryer (Thermo X16S-6564439-XS) to obtain 22.5 g of Chinese medicine freeze-dried powder. According to the dosage of clinical Chinese medicine compound, Example 1, Example 2, and Example 3, the method of converting the drug dosage by body surface area between humans and rats is as follows:

[0071] Rat dosage = adult dosage [g / (kg·d)] × 70kg × 0.018 / 0.2kg = 22.5g / 70kg × 70kg × 0.018 / 0.2 = 2.025 [g / (kg·d)]

[0072] 2.2 Preparation and administration of colchicine:

[0073] Colchicine was purchased from Xishuangbanna Pharmaceutical Co., Ltd. (Batch No.: 220708). According to the clinical colchicine dosage, adults take 1.5 mg per day. Colchicine tablets were ground into fine powder using a mortar and pestle and dissolved in 2 mL of distilled water. The method for converting the drug dosage of colchicine between humans and rats based on body surface area is as follows:

[0074] Rat dosage = adult dosage [mg / (kg·d)] × 60kg × 0.018 / 0.2kg = 1.5mg / 60kg × 60kg × 0.018 / 0.2 = 0.135 [mg / (kg·d)]

[0075] 2.3 Preparation and administration of LPS sterile solution:

[0076] LPS was purchased from Yuanye Biotechnology (Batch No.: JO7HS174755). 75ug LPS was weighed under sterile conditions and dissolved in 10mL sterile saline to prepare a 7.5ng / mL LPS sterile solution. 20uL of LPS solution was injected into the ankle joint of each rat every day.

[0077] 1. Effects of Chinese herbal compound on serum uric acid, creatinine, urea nitrogen, triglycerides, total cholesterol, high-density lipoprotein and low-density lipoprotein in rats with cold-dampness type gouty arthritis:

[0078] On the 28th day, after LPS was injected into the ankle joint, blood samples were collected from the abdominal aorta under anesthesia, and the blood supernatant was obtained by centrifugation at 3000 rpm / min for 15 min. The contents of uric acid, creatinine, urea nitrogen, triglycerides, total cholesterol, high-density lipoprotein and low-density lipoprotein in serum samples were detected by an automatic biochemical analyzer (BECKMAN COULTER AU2700).

[0079] Figure 1 It can be seen that compared with the control group, the blood uric acid concentration of the model group rats was significantly increased by feeding them with high-quality and high-purine feed ( P <0.01); compared with the model group, the blood uric acid concentration was significantly reduced after treatment with the drug combination Example 2 of the present invention ( P <0.01), indicating that the drug combination of the present invention has a good uric acid-lowering effect;

[0080] Figure 2 It can be seen that compared with the control group, the serum creatinine concentration of rats in the model group was significantly increased by feeding them with high-quality, high-purine feed ( P <0.001); compared with the model group, the serum creatinine concentration was significantly reduced after treatment with the drug combination Example 2 of the present invention ( P<0.001), indicating that the drug combination of the present invention has a good creatinine-lowering effect;

[0081] Figure 3 It can be seen that compared with the control group, the serum urea nitrogen concentration of the model group rats was significantly increased by feeding them with high-quality and high-purine feed ( P <0.001); Compared with the model group, the serum urea nitrogen concentration was significantly reduced after treatment with the drug combination Example 2 of the present invention ( P <0.001), indicating that the drug combination of the present invention has a good effect of reducing urea nitrogen;

[0082] Figure 4 It can be seen that compared with the control group, the serum triglyceride concentration of the model group rats was significantly increased by feeding them with high-quality and high-purine feed ( P <0.001); compared with the model group, the serum triglyceride concentration was significantly reduced after treatment with the drug combination Example 2 of the present invention ( P <0.01), indicating that the drug combination of the present invention has a good triglyceride-lowering effect;

[0083] Figure 5 It can be seen that compared with the control group, the serum total cholesterol concentration of the model group rats was significantly increased by feeding them with high-quality and high-purine feed ( P <0.001); compared with the model group, the serum cholesterol concentration was significantly reduced after treatment with the drug combination Example 2 of the present invention ( P <0.001), indicating that the drug combination of the present invention has a good cholesterol-lowering effect;

[0084] Figure 6 It can be seen that compared with the control group, the serum high-density lipoprotein concentration of the model group rats was significantly reduced by feeding them with high-quality, high-purine feed ( P <0.001); compared with the model group, the serum high-density lipoprotein concentration was significantly increased after treatment with the drug combination Example 2 of the present invention ( P <0.01), indicating that the drug combination of the present invention has a good effect of increasing high-density lipoprotein;

[0085] Figure 7 It can be seen that compared with the control group, the serum low-density lipoprotein concentration of the model group rats was significantly increased by feeding them with high-quality and high-purine feed ( P <0.001); Compared with the model group, the serum low-density lipoprotein concentration was significantly reduced after treatment with the drug combination Example 2 of the present invention ( P <0.001), indicating that the drug combination of the present invention has a good effect of reducing high density lipoprotein;

[0086] 2. Effects of Chinese herbal compound on ankle swelling, joint anterior-posterior diameter, and sole thickness in rats with cold-dampness gouty arthritis:

[0087] On the 25th day (i.e. before the injection of saline or LPS) and the 28th day (i.e. after the injection of saline or LPS), the volume, posterior diameter of the ankle joint and the thickness of the sole of the foot of all groups of rats were measured to calculate the swelling of the ankle joint of the rats. The specific calculation method is as follows:

[0088] Ankle swelling degree = (ankle volume after saline or LPS injection - ankle volume before saline or LPS injection) / ankle volume before saline or LPS injection) × 100%.

[0089] Figure 8 is the swelling rate of the left ankle joint of rats, Fig. 9 is the swelling rate of the right ankle joint of rats, Figure 8 , Fig. 9 It can be seen that compared with the control group, the tissue swelling rate of the rats in the model group was significantly increased by inducing cold-damp gouty arthritis in rats ( P <0.001); Compared with the model group, the swelling rate of the rat toes was significantly reduced after treatment with the drug combination Example 2 of the present invention ( P <0.001), indicating that the drug combination Example 2 of the present invention has a good anti-inflammatory and detumescent effect on cold-dampness type gouty arthritis.

[0090] During the experiment, the anteroposterior diameter of the ankle joint and the thickness of the sole of the foot of each group of rats were measured with a vernier caliper on the 1st, 7th, 14th, 21st and 28th day (i.e. before sampling) to calculate the growth rate of the anteroposterior diameter of the ankle joint and the growth rate of the sole thickness of the foot of the rats. The specific calculation method is as follows:

[0091] Ankle anteroposterior diameter growth rate = (the length of the anteroposterior diameter of the ankle of rats measured on the 7th / 14th / 21st / 28th day – the average of the anteroposterior diameter of the ankle of rats measured on the first day) / the average of the anteroposterior diameter of the ankle of rats measured on the first day × 100%;

[0092] The growth rate of sole thickness = (the thickness of rat soles measured every week - the average thickness of rat soles in the first week) / the average thickness of rat soles in the first week × 100%;

[0093] Fig.10 , Fig.11 is the growth rate of the anteroposterior diameter of the left and right ankle joints of rats, from Fig.10 It can be seen that compared with the control group, the anterior-posterior diameter of the left ankle joint of the rats in the model group increased significantly ( P <0.01); Compared with the model group, the anterior-posterior diameter of the left ankle joint of the rats treated with the drug combination of Example 2 of the present invention was significantly reduced ( P <0.01). Fig.11 It can be seen that compared with the control group, the anterior-posterior diameter of the right ankle joint of the rats in the model group was significantly increased ( P <0.001); Compared with the model group, the anterior-posterior diameter of the right ankle joint of the rats treated with the drug combination Example 2 of the present invention was significantly reduced ( P <0.001). This indicates that the drug combination Example 2 of the present invention has a good detumescent effect on cold-dampness type gouty arthritis.

[0094] Fig.12 , Fig.13 are the growth rates of the thickness of the left and right soles of rats, respectively. Fig.12 It can be seen that compared with the control group, the thickness of the left sole of the rats in the model group increased significantly ( P <0.01); Compared with the model group, the thickness of the left sole of the rats treated with the drug combination of the present invention Example 2 was significantly reduced ( P <0.01). Fig.13 It can be seen that compared with the control group, the thickness of the right sole of the rats in the model group increased significantly ( P <0.01); Compared with the model group, the thickness of the right sole of the rats treated with the drug combination of the present invention Example 2 was significantly reduced ( P <0.05). This indicates that the drug combination Example 2 of the present invention has a good detumescent effect on cold-dampness type gouty arthritis.

[0095] 3. Analgesic effect of Chinese herbal compound on rats with cold-dampness type gouty arthritis:

[0096] Inclined board test is an effective method for evaluating the motor function of rat hind limbs. In this patent application, this detection index can reflect the pain degree of arthritis in rats. First, the rat is placed on an inclined board padded with a rubber pad, so that the longitudinal axis of the rat body is placed parallel to the longitudinal axis of the inclined board, and the rat head is facing the elevated side of the inclined board. It is measured that the maximum angle of a normal rat climbing up the inclined board is 80 degrees and can be maintained for 5 seconds, so 80 degrees is set as the maximum climbing angle of a normal rat. With the establishment of the model and LPS induction, ankle pain is induced, and the ankle joint activity is reduced, resulting in a gradual decrease in the maximum climbing angle of the rat. The smaller the angle, the stronger the load-bearing capacity of the animal's hind limbs, which can reflect the aggravation of the pain degree.

[0097] Fig.14 It can be seen that compared with the control group, the maximum climbing angle of the model group rats was significantly reduced by inducing cold-damp gouty arthritis in rats ( P <0.001); Compared with the model group, the climbing angle of rats after treatment with the drug combination of the present invention Example 2 was significantly increased ( P <0.001), indicating that the drug combination Example 2 of the present invention has a good analgesic effect on cold-damp type gouty arthritis.

[0098] 4. Effects of Chinese herbal compound on joint morphology in rats with cold-dampness type gouty arthritis:

[0099] On the 28th day (before sampling), the morphological changes of the ankle joints of each group of rats were recorded.

[0100] Fig.15 It can be seen that compared with the control group, after induction of cold-dampness type gouty arthritis in rats, the ankle joints of the rats in the model group showed obvious swelling; compared with the model group, the swelling of the ankle joints of the rats was significantly alleviated after treatment with the drug combination Example 2 of the present invention, indicating that the drug combination Example 2 of the present invention has a good anti-inflammatory and detumescent effect on cold-dampness type gouty arthritis.

[0101] 5. Anti-inflammatory effect of Chinese herbal compound on rats with cold-dampness type gouty arthritis:

[0102] Interleukin IL-1β is the most critical cytokine during the onset of acute gouty arthritis, which leads to the generation and amplification of gout inflammation. By inhibiting the production of interleukin IL-1β, the cascade reaction of gout inflammatory response can be effectively alleviated and pain can be relieved. This experiment uses enzyme-linked immunosorbent assay (ELISA) to detect the content of interleukin IL-1β in rat serum inflammatory factor to evaluate the anti-inflammatory effect of the combined drug in this patent.

[0103] Fig.16 It can be seen that compared with the control group, the content of serum interleukin IL-1β in the model group rats increased significantly by inducing cold-damp type gouty arthritis in rats ( P <0.001); Compared with the model group, the content of serum interleukin IL-1β in rats treated with the drug combination of the present invention Example 2 was significantly reduced ( P <0.001), indicating that the drug combination Example 2 of the present invention has a good anti-inflammatory and analgesic effect on cold-dampness type gouty arthritis.

[0104] In summary, the Chinese medicinal compound obtained by the present invention has good anti-inflammatory and analgesic effects, can significantly reduce the swelling rate of the ankle joints of rats, improve the threshold of the inclined board test of rats (i.e. relieve pain), and can significantly reduce the content of uric acid, creatinine, urea nitrogen, triglycerides, total cholesterol, high-density lipoprotein, and low-density lipoprotein in serum, significantly improve the symptoms of gouty arthritis in rats, and can be used to prepare anti-inflammatory and analgesic drugs for preventing and treating gouty arthritis. In addition, the present invention has the characteristics of low cost and no pollution, and is suitable for industrial production.

[0105] The above technical features constitute the embodiments of the present invention, which have strong adaptability and implementation effect. Non-essential technical features can be added or reduced according to actual needs to meet the requirements of different situations.

Claims

1. A pharmaceutical composition for treating gouty arthritis, characterized in that: The medicinal materials are calculated by weight and consist of 9 to 20 parts of aconite, 10 to 40 parts of fenugreek, 10 to 40 parts of cinnamon twig, 10 to 40 parts of poria, 10 to 40 parts of smilax glabra, 10 to 40 parts of trachelospermum officinale, and 5 to 20 parts of codonopsis pilosula.

2. The pharmaceutical composition for treating gouty arthritis according to claim 1, characterized in that: The medicinal materials are calculated by weight and consist of 9 parts of aconite, 40 parts of fenugreek, 40 parts of cinnamon twig, 12 parts of poria, 40 parts of smilax glabra, 40 parts of trachelospermum officinale, and 5 parts of codonopsis pilosula.

3. The pharmaceutical composition for treating gouty arthritis according to claim 1, characterized in that: The medicinal materials are calculated by weight and consist of 12 parts of aconite root, 25 parts of fenugreek, 32 parts of cinnamon twig, 32 parts of poria, 25 parts of smilax glabra, 30 parts of trachelospermum officinale, and 10 parts of codonopsis pilosula.

4. The pharmaceutical composition for treating gouty arthritis according to claim 1, characterized in that: The medicinal materials are calculated by weight and consist of 20 parts of aconite root, 12 parts of fenugreek, 12 parts of cinnamon twig, 40 parts of poria, 10 parts of smilax glabra, 10 parts of trachelospermum officinale, and 15 parts of codonopsis pilosula.

5. The pharmaceutical composition for treating gouty arthritis according to any one of claims 1 to 4, characterized in that: Prepared as follows: The medicinal materials are prepared in required amounts, and water whose volume is 5 to 8 times that of the medicinal materials is added to the medicinal materials to obtain the medicine to be decocted; the medicine to be decocted is then decocted, and after the decocting is completed, the medicinal liquid is cooled and filtered to obtain a filtered soup; the filtered soup is concentrated to obtain a concentrated soup; the concentrated soup is dried to obtain a freeze-dried Chinese medicine powder, that is, a pharmaceutical composition for treating gouty arthritis.

6. The pharmaceutical composition for treating gouty arthritis according to claim 5, characterized in that: The prepared medicinal materials are first added with water having a volume multiple of 2.5 to 4 times that of the medicinal materials for soaking for 3 to 4 hours. After the soaking, the required amount of water is added to the medicinal materials to obtain the decocted medicine.

7. The pharmaceutical composition for treating gouty arthritis according to claim 6, characterized in that: The decoction method adopts the reflux decoction method, and the decoction time is 2 hours to 2.5 hours; or / and, the volume multiple of the concentrated soup is one fifteenth to one tenth of the medicine to be decocted.

8. The pharmaceutical composition for treating gouty arthritis according to claim 7, characterized in that: The mass ratio of the Chinese medicine freeze-dried powder to the medicinal material is 0.1 to 0.2:1; or / and, the freeze-drying temperature is -40°C, and the freezing time is 20h to 24h.

9. A method for preparing a pharmaceutical composition for treating gouty arthritis according to claim 1 or 2 or 3 or 4 or 6 or 7 or 8, characterized in that: Proceed as follows: The medicinal materials are prepared in required amounts, and water whose volume is 5 to 8 times that of the medicinal materials is added to the medicinal materials to obtain the medicine to be decocted; the medicine to be decocted is then decocted, and after the decocting is completed, the medicinal liquid is cooled and filtered to obtain a filtered soup; the filtered soup is concentrated to obtain a concentrated soup; the concentrated soup is dried to obtain a freeze-dried Chinese medicine powder, that is, a pharmaceutical composition for treating gouty arthritis.

10. Use of the pharmaceutical composition for treating gouty arthritis according to any one of claims 1 to 8 in the preparation of a medicament for treating gouty arthritis.

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