Medicine for treating hyperuricemia and gout

Abstract

The invention relates to a medicine for treating hyperuricemia and gout, which is prepared from fried rhizoma atractylodis, giant knotweed rhizome, winged euonymus twig, salted golden cypress, coix seed, glabrous greenbrier rhizome, turmeric root-tuber, red-rooted salvia root, pawpaw, clematis root, twotooth achyranthes root, dried orange peel and fried white paeony root, has good effects of clearing heat, promoting diuresis, dispersing blood stasis and dredging collaterals, and is simple in composition, reasonable in compatibility, appropriate in cold and warm, free of toxic and side effects and free of toxic and side effects. The traditional Chinese medicine composition has the effects of eliminating dampness, excreting dampness and dissipating dampness, protecting spleen and stomach and regulating qi and blood, and has definite curative effect and high safety when being used for clinically treating the damp-heat stasis type gout.

Description

Technical Field

[0001] The invention belongs to the technical field of Chinese medicine preparation, and relates to a drug for treating hyperuricemia and gout-like diseases, and in particular to a drug for treating hyperuricemia and gout based on Chinese medicine. Background Art

[0002] Uric acid is the final metabolite of purine compounds in humans. Hyperuricemia refers to a pathological state in which uric acid accumulates in the blood due to disordered purine metabolism, excessive uric acid secretion or reduced uric acid excretion. Hyperuricemia is the pathological basis for gout. Gout is a crystal-related arthritis caused by long-term hyperuricemia, in which tiny crystals of monohydrated sodium urate in an oversaturated state in the body precipitate and deposit in joints, around joints, under the skin, and in the kidneys.

[0003] As people's living standards improve, their eating habits and lifestyles change, the incidence of hyperuricemia has gradually increased. It has become the second largest metabolic disease after diabetes, and is showing a trend of younger people. The incidence in coastal and plateau areas is higher than in inland areas. The occurrence of gout and hyperuricemia is closely related to metabolic syndrome, including hypertension, insulin resistance, type 2 diabetes, hyperlipidemia, central obesity and other diseases; at the same time, gout and hyperuricemia are also independent risk factors for diabetes, cardiovascular and cerebrovascular diseases, chronic kidney disease, erectile dysfunction, obstructive sleep apnea syndrome and other diseases.

[0004] The overall treatment principle and goal of modern medicine for hyperuricemia and gout is to maintain the blood uric acid level to meet the target, reduce gout attacks, and reduce the occurrence of complications. Uric acid-lowering drugs are mainly divided into two categories: drugs that inhibit uric acid production and drugs that promote uric acid excretion.

[0005] Among drugs that inhibit uric acid production, allopurinol is prone to allergic reactions and is not recommended for patients with positive HLA-B*5801 genes. Febuxostat is suitable for long-term treatment of hyperuricemia in gout patients, but is not recommended for hyperuricemia without clinical symptoms. The most common adverse reaction of febuxostat is abnormal liver function, and liver function needs to be tested regularly during use. Compared with allopurinol, febuxostat increases the risk of death from cardiovascular events in gout patients. Among drugs that promote uric acid excretion, benzbromarone should not be taken during an acute attack of gout.

[0006] In addition, nonsteroidal anti-inflammatory drugs such as colchicine are the first-line drugs for acute gout attacks, but they should be used with caution in the elderly, patients with renal insufficiency, and patients with a history of peptic ulcers, bleeding, and perforation. Oral or injectable glucocorticoids are recommended for patients who are intolerant to nonsteroidal anti-inflammatory drugs or whose condition is difficult to control, but the course of treatment generally does not exceed 10 days.

[0007] Although modern medicine can relieve some symptoms of gout, long-term use can cause adverse reactions and there are many contraindications, and the clinical treatment effect is not ideal. Therefore, finding a drug with significant efficacy, few adverse reactions and a wide range of use has become an urgent problem to be solved.

[0008] The name of the disease "gout" in Chinese medicine was first seen in "Gezhi Yu Lun·Gout Theory", which said: "Gout is mostly caused by the blood boiling due to heat, and then wading in cold water, standing in wet places, fanning yourself to cool down, or lying in the wind. The coldness outside the body makes the hot blood cold, and the blood becomes dirty and astringent, so it hurts." Records of gout-related symptoms can also be found in related discussions of "arthralgia", "foot itch", "Baihu Lijiefeng" and other related discussions in Chinese medicine. The ancients believed that the occurrence of gout was mostly related to the invasion of external evils, and the deficiency of the body's body defense, which led to the blockage of meridians and the loss of nourishment to the limbs. Although external evils are the cause of the disease, the root cause is the body's weakness and inability to withstand the invasion of evils.

[0009] The clinical symptoms of hyperuricemia before gout attack are usually not obvious, which is considered as "not sick" or "hidden evil" in traditional Chinese medicine. From the perspective of traditional Chinese medicine, elevated blood uric acid is caused by fullness in the middle of the body, poor circulation of qi and blood, accumulation of turbidity, or further flow into the meridians, which belongs to the category of "turbid uric acid". Abnormal blood uric acid is caused by eating too much fatty and sweet food, damp heat, and if it further flows into the joints, gout will occur. Therefore, it is based on internal damp heat, which hurts the inside without external invasion.

[0010] Modern research has confirmed that the occurrence of gout is closely related to the levels of inflammatory factors such as IL-6, IL-1β, IL-8, and TNF-α. Dai Tingting et al. (Research progress on the treatment of gout with single Chinese medicine based on NLRP3 inflammasome and NF-B signaling pathway [J]. Hubei Journal of Traditional Chinese Medicine, 2022, 44(4): 51-54.) believed through pharmacological research that the key mechanism of Chinese medicine in treating gout lies in inhibiting inflammatory factors. At present, through various mining methods, it has been found that Chinese medicine has the advantages of multiple targets and few adverse reactions. The use of Chinese medicine to treat gout has been recognized by more and more people in the industry.

[0011] Simiao Powder comes from the book Cheng Fang Fang Du written by Zhang Bingcheng. It is composed of Atractylodes, Phellodendron, Achyranthes bidentata, and Coix seed. It is good at clearing heat and removing dampness, and has a good effect in the clinical treatment of damp-heat arthralgia. In the prescription, Phellodendron is good at clearing dampness and heat in the lower jiao, and is the main medicine; Atractylodes lancea strengthens the spleen and helps to treat the root of dampness, and dries dampness to remove the symptoms of dampness and obstruction, and is the minister medicine; Coix seed removes dampness and heat and benefits the meridians; Achyranthes bidentata guides the medicine downward into the lower jiao, and is the meridian-guiding medicine, which treats swelling and pain in the feet and knees caused by dampness and heat. Therefore, Simiao Powder is often used as a basic prescription in clinical practice to treat damp-heat arthralgia such as hyperuricemia and gout.

[0012] Liu Yamei et al. (Therapeutic effect of Simiao Pills on gouty arthritis and its impact on laboratory indicators [J]. World Chinese Medicine, 2018, 13(6): 1428-1431.) and Zeng Liying et al. (Exploration of the mechanism of action of Simiao Pills in the treatment of hyperuricemia based on network pharmacology and molecular docking [J]. Journal of Southern Medical University, 2021, 41(4): 579-587.) have shown that berberine, one of the main ingredients of Simiao Pills, can inhibit the PI3K / AKT signaling pathway to reduce the levels of IL-6, IL-1β, IL-8, and TNF-α.

[0013] Lin X et al. (Simiao Decoction Alleviates Gouty Arthritis by Modulating Proinflammatory Cytokines and the Gut Ecosystem [J]. Frontiers in Pharmacology, 2020, 11: 955.) believe that Simiao Pills can reduce intestinal cell apoptosis and restore the intestinal ecosystem by regulating the expression of TNF-α to achieve the effect of treating gout.

[0014] However, Si Miao San still has shortcomings in the following aspects:

[0015] 1. Limited applicable syndromes: In clinical practice, the syndromes of gout patients are relatively complex, involving multiple factors such as spleen deficiency, liver depression, and kidney deficiency. Simiao San is mainly suitable for gout of damp-heat type, and may not be effective for gout with damp-heat and other syndromes. Its clinical applicability is not high when used alone.

[0016] 2. Relatively simple composition: The drug composition of Simiao Powder is relatively small. For the concurrent symptoms such as blood stasis, qi stagnation, phlegm and dampness that may occur in gout patients, the effect of Simiao Powder is relatively limited.

[0017] 3. Insufficient protection for the spleen and stomach: The bitter and cold nature of Phellodendron chinense in Simiao Powder may damage the spleen and stomach if used for a long time. Gout patients often need to take medication for a long time, and impaired spleen and stomach function may affect the absorption and efficacy of the drug, and even cause adverse reactions such as nausea, vomiting, and diarrhea.

[0018] 4. Relatively limited efficacy: Although studies have shown that Simiao Powder is effective in treating gout and can reduce blood uric acid levels and the incidence of adverse reactions, the symptoms of joint redness, swelling, heat and pain are obvious during the acute attack of gout. In addition to damp-heat pathogens, there are also pathological products such as turbidity, blood stasis and heat toxins (Discussion on the understanding of gout from the perspective of "turbidity and blood stasis" [J]. Liaoning Journal of Traditional Chinese Medicine, 2019, 46(06):1179-1181.). Simiao Powder is a relatively mild drug for treating damp-heat syndrome. It is not enough to quickly relieve symptoms, and lacks the power to clear away heat and toxic substances, and to remove blood stasis and dredge the meridians. Therefore, it still needs to be used in combination with other Chinese medicines. Summary of the invention

[0019] The purpose of the present invention is to provide a medicine for treating hyperuricemia and gout, which can strengthen the effect of removing blood stasis and unblocking collaterals on the basis of clearing away heat and removing dampness, so as to adapt to the complex condition of hyperuricemia and gout of damp-heat and blood stasis type and effectively alleviate clinical symptoms.

[0020] To achieve the above-mentioned purpose of the invention, the present invention takes Simiao Powder, a commonly used traditional Chinese medicine for treating damp-heat obstruction type arthralgia, as the basic prescription, adds other clinical experience medicines on the basis, and takes fried Atractylodes lancea, Polygonum cuspidatum, Phellodendron chinense, Salt-cured Phellodendron chinense, Coix seeds, Smilax glabra, Curcuma aromatica, Salvia miltiorrhiza, Papaya, Clematidis, Achyranthes bidentata, Tangerine peel and fried White Peony Root as raw materials to prepare a medicine for treating hyperuricemia and gout, which has unique therapeutic effect in clinical treatment of hyperuricemia and gout.

[0021] Furthermore, the medicine for treating hyperuricemia and gout of the present invention is prepared from the following raw materials in parts by weight: 10-20 parts of stir-fried atractylodes, 10-20 parts of polygonum cuspidatum, 10-30 parts of euphorbia pulex, 10-20 parts of salt phellodendron, 20-50 parts of coix seed, 20-50 parts of smilax glabra, 10-20 parts of turmeric, 10-20 parts of salvia miltiorrhiza, 10-20 parts of papaya, 10-20 parts of clematis, 10-20 parts of achyranthes bidentata, 20-50 parts of tangerine peel, and 10-30 parts of stir-fried white peony root.

[0022] Furthermore, in the medicine for treating hyperuricemia and gout, the weight proportions of each raw material are: stir-fried Atractylodes lancea 12-18, Polygonum cuspidatum 12-18, Phellodendron chinense 15-25, Phellodendron chinense 12-18, Coix lachryma-jobi 25-40, Smilax glabra 25-40, Curcuma aromatica 12-18, Salvia miltiorrhiza 12-18, Papaya 12-18, Clematidis 12-18, Achyranthes bidentata 12-18, Tangerine peel 25-40, and stir-fried White Peony Root 15-25.

[0023] More specifically, in the medicine for treating hyperuricemia and gout, the weight proportions of each raw material are preferably 15 of stir-fried atractylodes, 15 of polygonum cuspidatum, 20 of euphorbia pulex, 15 of salt phellodendron, 30 of coix seed, 30 of smilax glabra, 15 of curcuma, 15 of salvia miltiorrhiza, 15 of papaya, 15 of clematis, 15 of achyranthes bidentata, 30 of tangerine peel, and 20 of stir-fried white peony root.

[0024] The selection and dosage of the above various raw materials are obtained by the inventor after a lot of exploration and summary. Practice has proved that various raw materials have good therapeutic effects within the above weight ranges.

[0025] The main causes of gout are congenital deficiency, deficiency of vital energy, and malnutrition of meridians; or being affected by external evil, which blocks the meridians and causes poor circulation of qi and blood, leading to pain and swelling in the joints, tendons, bones, and muscles; improper diet, overeating of fatty and greasy foods, which damage the spleen and stomach, cause phlegm heat, and phlegm and blood stasis, leading to stagnation of meridians, poor circulation of qi and blood, and the onset of arthritis.

[0026] The main pathogenesis of gout is generally: wind, cold, dampness, heat, phlegm, stasis, and deficiency. Under certain conditions, they influence each other and transform each other, causing meridian obstruction and poor circulation of qi and blood. The pathogenesis of gout is common in the period between deficiency and excess. The pathogenic nature of wind, cold, dampness and heat is different, or there is a partial excess, and its clinical manifestations are also different. Among them, dampness and stasis are the core, running through the pathogenesis from beginning to end, with deficiency and excess mixed, spleen and kidney deficiency as the root, dampness and heat obstruction, phlegm and blood stasis as the sign. In addition, it is also related to factors such as heredity, constitution, diet, exogenous infection, environment, emotions, fatigue, etc. The disease is located in the meridians on the surface of the muscles, and then deep to the tendons and bones, and the spleen, liver and kidney are injured over time.

[0027] The treatment of hyperuricemia requires overall diagnosis and treatment, grasping the method of clearing the bowels and purging turbidity, distinguishing the deficiency and excess, and adding or subtracting medication according to the urgency and slowness. In excess, clear the bowels and remove stagnation, and in deficiency, strengthen metabolism. In an emergency, clear dampness and heat, and eliminate evil, and in a slow manner, regulate the spleen and stomach, and attack and supplement at the same time. With the main line of purging turbidity, promoting dampness, removing blood stasis and detoxification, regulating the spleen and kidney, and correcting the root and clearing the source, it runs through the whole process.

[0028] The present invention is based on the theory of traditional Chinese medicine and clinical experience summary, with Si Miao San as the basis, and is modified according to the symptoms. In the prescription, Phellodendron chinense, Atractylodes macrocephala, Coix seeds, and Achyranthes bidentata are the original prescription of Si Miao San, and Polygonum cuspidatum, Chaenomeles sinensis, Clemati radix, and Smilax glabra are added to clear away heat and dampness, relax muscles and activate collaterals, and Radix Angelicae Pubescentis, Salvia miltiorrhiza, and Radix Curcumae promote blood circulation and remove blood stasis, promote joints, and Radix Paeoniae Alba nourishes yin and relieves pain, restricts the pungent and strong nature of the prescription, and Tangerine peel is used to strengthen the transportation of the middle jiao, restores the normal transportation and distribution of body fluids, and makes dampness and turbidity have no way to survive. The medicine is cold and warm, and is used to dry dampness, penetrate dampness, and disperse dampness, protect the spleen and stomach, and harmonize qi and blood, and attaches importance to the application of blood circulation and stasis removal method; dampness is eliminated to relieve turbidity and toxicity, and blood stasis is eliminated to dredge blood vessels, so that dampness is removed and turbidity is difficult to form, and stasis is resolved and heat disappears by itself, which is more comprehensive than the basic prescription and has a wider application.

[0029] The present invention can adopt conventional preparation methods of Chinese medicine preparations to prepare the above-mentioned raw materials of the present invention into any conventional oral dosage form in pharmacy, but these dosage forms cannot be used to limit the protection scope of the present invention. It should be emphasized that before preparing any dosage form, the active components of the Chinese medicine of the present invention need to be prepared first.

[0030] The specific preparation method of making the above-mentioned raw materials into the active components of the medicine of the present invention is: decocting the raw materials with water, filtering to obtain an extract, concentrating and drying to obtain the active components of the medicine.

[0031] Among them, further, it is preferred that the raw material drug is decocted with water twice, the decoctions are combined, filtered, concentrated and dried to obtain the active pharmaceutical ingredient.

[0032] Furthermore, when adding water to decoct the medicine, it is preferred that the amount of water used each time is 8 to 12 times the weight of the raw material medicine, and each decoction is performed for 1 to 2 hours.

[0033] Generally, the present invention is to concentrate the extract under reduced pressure into a pharmaceutically active component having a relative density of 1.10 to 1.30 at room temperature.

[0034] The present invention can further prepare the obtained active pharmaceutical ingredients into any conventional oral dosage form, such as tablets, capsules, granules, pills, mixtures, powders, syrups or decoctions, by conventional Chinese medicine preparation methods and adding pharmaceutically acceptable excipients or carriers.

[0035] In the medicine of the present invention, Atractylodes lancea is bitter and pungent in nature, can dry and strengthen the spleen, can purge dampness in the upper burner, and soothe the stomach without making it too much; Polygonum cuspidatum is bitter and cold, can clear away heat and resolve phlegm, promote dampness and detoxify, disperse blood stasis and relieve pain, and can treat phlegm, dampness, blood stasis and heat; Glechoma longituba is bitter and cold, has a special blood-breaking nature, and can treat rheumatoid arthritis and various arthritis. The three medicines are the main medicines, which can clear away heat and dry dampness, resolve blood stasis and dredge the meridians.

[0036] Phellodendron chinense is bitter and cold in nature, can relieve hyperactive yang, remove dampness and heat to strengthen kidney yin; Coix seed is sweet and mild, white in color and enters the lungs, sweet in taste and enters the spleen, can relax muscles and remove dampness, detoxify and disperse knots; Smilax glabra is sweet and mild in nature, can detoxify and remove dampness, and open up the joints; Salvia miltiorrhiza and Curcuma aromatica are bitter and cold, can both activate blood circulation and cool blood, clear the heart and relieve depression, break up blood and lower qi, remove blood stasis and relieve pain; Papaya is sour and warm in nature, can soothe the liver and relax muscles, harmonize the stomach and eliminate dampness; Clematidis is pungent in taste, has a strong power to move around, can search out dampness in the meridians, and relieve depressed heat; it is warm in nature, can warm and dredge the meridians, warm the yang and eliminate dampness, help the efficacy of the medicine, and can prevent excessive cold from damaging the yang, and avoid lingering diseases that are difficult to cure; they are all ministers, helping the monarch to dispel wind, remove dampness, dredge the meridians, clear away heat, detoxify and resolve blood stasis.

[0037] Tangerine peel, Achyranthes bidentata, and white peony root are used as adjuvants. Tangerine peel is bitter and warm in nature, which can regulate qi and resolve phlegm, wake up the spleen and help digestion, strengthen the central region, protect the spleen and stomach qi, and eliminate the source of phlegm; Achyranthes bidentata can nourish the liver and kidneys, promote blood circulation and dredge the menstruation, strengthen the body and eliminate evil at the same time, and guide the medicine downward, so it is suitable for patients with gout in the tendons and bones; white peony root is sweet in taste and cold in nature, which can clear the deficiency fire and nourish the yin fluid. It is compatible with papaya to prevent a large amount of diuretic drugs from damaging the yin.

[0038] The above medicines are used together to clear away heat and dampness, dissipate blood stasis and dredge meridians, and expel evil without hurting the body. The prescription composition is concise, the compatibility is reasonable, the cold and warm are appropriate, and the dampness is dried, penetrated and dispersed at the same time, protecting the spleen and stomach, harmonizing qi and blood, and emphasizing the application of blood circulation and stasis removal. The medicine in the prescription does not contain toxic herbs, and there are no incompatibility taboos such as the 18 anti-reactions and 19 fears. The drugs have legal standards, are widely distributed, have abundant resources, and are low in price.

[0039] The medicine of the present invention is used for patients with gout, hyperuricemia and other diseases which are caused by damp-heat and blood stasis, with symptoms such as fatigue, drowsiness, heaviness of limbs, pain in tendons and bones, dark tongue, greasy tongue coating and the like. It has good effects of clearing away heat and dampness, removing blood stasis and dredging collaterals. Compared with commonly used Western medicines in clinical practice, it has significantly reduced side effects, significantly improved symptoms, and no obvious adverse reactions. Clinical practice has shown that it has good safety and significant clinical efficacy.

[0040] Compared with Simiao Powder, the drug of the present invention has obvious advantages in improving syndrome scores, and its efficacy in correcting some abnormal indicators is better, which is specifically reflected in the following advantages:

[0041] 1. Wide range of applicable syndromes: The drug of the present invention is aimed at hyperuricemia and gout of damp-heat and blood stasis type. On the basis of clearing away heat and removing dampness, it strengthens the effect of removing blood stasis and unblocking collaterals. It can better adapt to complex clinical conditions and can also exert a good therapeutic effect on patients with concurrent symptoms such as blood stasis, qi stagnation, phlegm and dampness.

[0042] 2. Rich composition and reasonable compatibility: on the basis of Simiao Powder, the medicine of the present invention is added with Rhizoma Smilacis Glabrae and Polygonum Cuspidatum for detoxification and dampness removal, and joints are smooth. Polygonum Cuspidatum can further disperse blood stasis and relieve pain, and has a laxative effect, and treats phlegm-dampness, blood stasis and heat, so that dampness and turbidity toxic evil can be eliminated from the two excrements; Salvia Miltiorrhiza tastes bitter and red in color and walks in the blood, and blood circulation and blood stasis can produce new blood, and it is good at cooling blood and relieving swelling; Feather of Astragalus and Curcuma Radix for removing blood stasis and dredging collaterals can make the meridians smooth, and the qi and blood circulate, and blood stasis is self-resolving, and dampness evil disappears therewith; Clematidis warms and dredges the meridians, warms the yang and dispels dampness, and can relieve depression and heat, and anti-cold drugs hurt yang; Tangerine peel regulates qi and invigorates the spleen, protects the spleen and stomach, white peony root reaches the liver qi, tonifies yin and protects yin, papaya relaxes the muscles and activates the collaterals, and tonifies the stomach and produces body fluid, preventing the person who is warm and dry from infiltrating and damaging yin fluid. All medicines are used together, and the cold and warm are appropriate, and both attack and supplement are used, and the effects of clearing away heat and dampness, removing blood stasis and dredging collaterals can be fully exerted.

[0043] 3. Protect the spleen and stomach with high safety: The medicine of the present invention pays attention to protecting the spleen and stomach in the prescription, and uses drugs such as dried tangerine peel, atractylodes, papaya, coix seed, white peony root to dry dampness and eliminate dampness to relieve spleen distress, regulate qi and soothe the liver to help spleen function, and uses warm drugs such as atractylodes, clematis, papaya to balance the cold and heat ratio in the prescription to avoid excessive cold and damage to spleen yang, which can reduce the stimulation of drugs to the spleen and stomach and improve patients' tolerance and compliance. At the same time, the medicine of the present invention has high safety, few adverse reactions, and is suitable for long-term use.

[0044] 4. Exact therapeutic effect: Clinically verified, the drug of the present invention has an exact therapeutic effect on gout of damp-heat and blood stasis type, can effectively relieve clinical symptoms, reduce VAS scores, improve UA, ESR, CRP and inflammatory factor levels, and improve the quality of life of patients. Implementation

[0045] The specific implementation of the present invention is further described in detail below in conjunction with the examples. The following examples are only used to more clearly illustrate the technical solution of the present invention so that those skilled in the art can well understand and utilize the present invention, but not to limit the protection scope of the present invention.

[0046] The production processes, experimental methods or detection methods involved in the embodiments of the present invention, unless otherwise specified, are all conventional methods in the prior art, and their names and / or abbreviations are all conventional names in the field, and are very clear and unambiguous in the relevant application fields. Technical personnel in the field can understand the conventional process steps based on the names and apply the corresponding equipment, and implement them according to conventional conditions or the conditions recommended by the manufacturer.

[0047] The various instruments, equipment, raw materials or reagents used in the embodiments of the present invention are not particularly limited in terms of their sources, and are all conventional products that can be purchased through regular commercial channels, or can be prepared according to conventional methods well known to those skilled in the art. Example

[0048] Example 1

[0049] Take 15g of the selected stir-fried Atractylodes lancea, 15g of Polygonum cuspidatum, 20g of Radix Phellodendri, 15g of Phellodendron chinense, 30g of Coix seeds, 30g of Smilax glabra, 15g of Curcuma, 15g of Salvia miltiorrhiza, 15g of Papaya, 15g of Clematidis, 15g of Achyranthes bidentata, 30g of Tangerine peel, and 20g of stir-fried White Peony Root, add water and decoct twice, each time with 2500mL of water, and decoct for 1.5h. Combine the two decoctions, filter, and concentrate under reduced pressure to a relative density of 1.2 to 1.3 (room temperature), spray dry, add an appropriate amount of dextrin or powdered sugar, and mix well to prepare granules.

[0050] Example 2

[0051] Take the screened stir-fried Atractylodes 18g, Polygonum cuspidatum 18g, Radix Phellodendri 25g, Phellodendron chinense 12g, Semen Coix 40g, Rhizoma Smilacis Glabrae 25g, Radix Curcumae 18g, Radix Salviae Miltiorrhizae 18g, Fructus Chaenomelis 12g, Radix Clematidis 12g, Radix Achyranthis Bidentatae 12g, Pericarpium Citri Reticulatae 30g, Radix Paeoniae Alba 15g, add water and decoct 2 times, each time with 2500mL of water, decoct 1.5h. Combine two decoctions, filter, and be concentrated under reduced pressure to a dry paste to obtain active pharmaceutical ingredients. Add appropriate amount of sucrose, starch, dextrin and magnesium stearate to the active pharmaceutical ingredients, mix to form granules, and tablets are made into tablets.

[0052] Example 3

[0053] Take 12g of the selected stir-fried Atractylodes lancea, 12g of Polygonum cuspidatum, 15g of Radix Phellodendri, 18g of Phellodendron chinense, 25g of Coix seeds, 40g of Smilax glabra, 12g of Curcuma, 12g of Salvia miltiorrhiza, 18g of Papaya, 18g of Clematidis, 18g of Achyranthes bidentata, 25g of Tangerine peel, and 25g of stir-fried Paeonia lactiflora, add water and reflux to extract twice, each time with 2500mL of water, and extract for 1.5h. Combine the two extracts, filter, and concentrate under reduced pressure to a dry paste to obtain the active ingredient of the drug, add the auxiliary materials calcium carbonate and starch to mix, dry and grind into fine powder, sieve, and put into capsules to make capsules.

[0054] Example 4

[0055] Patients with gout, hyperuricemia and other symptoms of damp-heat and blood stasis were taken as research subjects, and the clinical efficacy of the medicine prepared by the present invention was observed.

[0056] 1. Research subjects

[0057] A total of 100 patients with gout of damp-heat and blood stasis type who were admitted to the Department of Endocrinology of Shanxi Provincial Hospital of Traditional Chinese Medicine from January 2022 to June 2023 were included and randomly divided into a control group and an experimental group, with 50 cases in each group. One patient in the control group dropped out due to unexplained loss of follow-up, and 49 cases were finally included in the statistical analysis. One patient in the experimental group voluntarily withdrew from the study, and 49 cases were finally included in the statistical analysis. There was no statistically significant difference in the general information of the two groups of patients ( P >0.05), which are comparable, as shown in Table 1.

[0058]

[0059] 2 Diagnostic criteria

[0060] Western medicine diagnosis refers to the "Guidelines for Primary Diagnosis and Treatment of Gout and Hyperuricemia (2019)"; Traditional Chinese medicine diagnosis refers to the diagnostic criteria for gout damp-heat and blood stasis type formulated in the "Standards for Diagnosis and Efficacy of Traditional Chinese Medicine Diseases and Syndromes".

[0061] Main symptoms: redness, swelling, heat and pain in the small joints of the lower limbs, tenderness and refusal to press, and movement disorders; Secondary symptoms: milder during the day and worse at night, restlessness, thirst but no desire to drink, relief from coolness, fatigue, bitter and greasy taste in the mouth, sticky stools, yellow and red urine; Tongue and pulse: dark tongue, or with petechiae and ecchymosis, yellow and greasy, slippery and rapid pulse.

[0062] The syndrome can be clearly differentiated if the main symptom and three secondary symptoms are present.

[0063] 3. Treatment

[0064] Both groups were given routine health guidance in accordance with the "Guidelines for the Diagnosis and Treatment of Gout and Hyperuricemia in Primary Care (2019)", and were advised to eat a low-purine diet, drink plenty of water (more than 2000 ml per day), get enough rest, quit smoking and drinking, avoid fatigue, keep warm, and relax.

[0065] The control group was given oral Simiao Pills (National Medicine Standard No. Z22024960), 6 g / time, twice / day, after meals.

[0066] The test group was orally administered with the granules of Example 1 of the present invention, which were dissolved in 400 ml of water and divided into two portions for oral administration, 200 ml / time, 2 times / day, after meals.

[0067] The treatment course for both groups was 2 weeks.

[0068] 4. Criteria for determining efficacy

[0069] The efficacy standards for the two groups of patients after treatment were established based on the "Guidelines for Clinical Research of New Chinese Medicines (Trial)".

[0070] Clinical recovery: TCM symptoms and signs disappear or basically disappear, major biochemical indicators are normal, and the symptom score reduction rate is ≥95%;

[0071] Markedly effective: TCM symptoms and signs are significantly improved, major biochemical indicators are basically normal, and the symptom score reduction rate is 70%≤<95%;

[0072] Effective: TCM symptoms and signs have improved, major biochemical indicators have improved, 30%≤symptom score reduction rate<70%;

[0073] Ineffective: TCM symptoms, signs, and biochemical indicators did not improve or even worsened, and the symptom score reduction rate was <30%.

[0074] Symptom score reduction rate (%) = [(pre-treatment score - post-treatment score) ÷ pre-treatment score] × 100%.

[0075] Total effective rate (%) = [(number of clinically cured cases + number of markedly effective cases + number of effective cases) ÷ total number of cases] × 100%.

[0076] 5. Observation indicators

[0077] 5.1 TCM Syndrome Scoring

[0078] With reference to the Guiding Principles for Clinical Research of New Chinese Medicines (Trial Implementation), quantitative scores were given for joint pain, tenderness, swelling, fever, limited joint movement and some secondary symptoms such as fatigue, bitter taste in the mouth, sticky stool and yellow and red urine of small joints of lower limbs of the two groups of patients before and after treatment. The severity was divided into 0, 2, 4 and 6 points (none = 0 point, mild = 2 points, moderate = 4 points, severe = 6 points). A TCM syndrome scoring scale was developed to compare the TCM syndrome scores of the two groups of patients before and after treatment.

[0079] 5.2 VAS score

[0080] The visual analogue scale (VAS) was used to evaluate the pain of the two groups of patients before and after treatment, with a score of 0 to 10, where 0 indicated no pain; 1 to 2 indicated mild pain, which was tolerable and allowed a normal life and sleep; 3 to 4 indicated moderate pain, which affected sleep slightly and required analgesics; 5 to 6 indicated severe pain, which affected sleep and required narcotic analgesics; 7 to 8 indicated severe pain, which affected sleep severely and was accompanied by other symptoms; 9 to 10 indicated unbearable pain, which seriously affected sleep and was accompanied by other symptoms or passive posture.

[0081] 5.3 Laboratory indicators

[0082] Fasting venous blood was drawn from the two groups of patients before treatment and in the morning on the 14th day after treatment. Serum was collected for detection of uric acid (UA) and C-reactive protein (CRP). Anticoagulated plasma was used to detect erythrocyte sedimentation rate (ESR). Flow cytometry was used to detect inflammatory factors such as interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α).

[0083] 6. Statistical methods

[0084] SPSS 22.0 statistical software was used for analysis. The measurement data were in accordance with normal distribution and expressed as mean ± standard deviation ( ), within-group comparisons were made using paired t Test, comparison between groups using independent samples t For test, two-sided test was selected for comparison; count data were expressed as rate (%), and chi-square test was used for comparison between groups ( x 2 test). P <0.05 indicated that the difference was statistically significant.

[0085] 7. Results

[0086] 7.1 Clinical efficacy

[0087] The clinical efficacy of the experimental group after treatment was better than that of the control group ( P <0.05), see Table 2 for the specific results.

[0088]

[0089] 7.2 TCM Syndrome Score

[0090] After treatment, the TCM syndrome scores of both groups of patients decreased compared with those before treatment, and the decrease in the experimental group was greater than that in the control group, with a statistically significant difference ( P <0.05), see Table 3 for details.

[0091]

[0092] Compared with the group before treatment, * P <0.05, ** P <0.01; compared with the control group after treatment, △ P <0.05.

[0093] 7.3 Laboratory indicators and VAS scores

[0094] Compared with the group before treatment, the UA, ESR, CRP and VAS scores of the two groups were significantly reduced after treatment ( P <0.01); compared with the control group, the UA, ESR, CRP and VAS scores of the experimental group were reduced, and the difference was statistically significant ( P <0.05), the results are shown in Table 4.

[0095]

[0096] Compared with the group before treatment, * P <0.01; compared with the control group after treatment, △ P <0.05.

[0097] 7.4 Inflammatory Factors

[0098] After treatment, the levels of inflammatory factors in both groups were significantly lower than those before treatment ( P <0.01, and the levels of inflammatory factors in the experimental group were lower than those in the control group ( P <0.05), see Table 5.

[0099]

[0100] Compared with the group before treatment, * P <0.01; compared with the control group after treatment, △ P <0.05.

[0101] Gout is a metabolic disease caused by excessive accumulation of uric acid levels in the joint capsule, synovium, cartilage, etc. It is often related to purine metabolism disorders, decreased uric acid excretion, and abnormally elevated blood uric acid. It has an acute onset, severe pain, and is difficult to heal. It can cause symptoms such as renal damage, tophi formation, and joint deformities, greatly reducing the patient's quality of life.

[0102] Modern research shows that there are activation and expression of multiple inflammatory factors in gout patients, so early use of symptomatic treatments such as colchicine, nonsteroidal anti-inflammatory drugs, and glucocorticoids can bring short-term benefits, but long-term use of the above drugs will cause obvious adverse reactions to the body, especially long-term use will lead to risks of liver and kidney damage, cardiovascular and cerebrovascular diseases, gastrointestinal bleeding, drug resistance, and recurrence after discontinuation of medication.

[0103] Traditional Chinese medicine has multiple targets for gout treatment, few adverse reactions, and good clinical efficacy. The drug of the present invention treats gout of damp-heat stasis type, and is superior to the control group in relieving clinical symptoms, reducing VAS scores, and improving UA, ESR, CRP and inflammatory factor levels, with good safety. The mechanism of action may be related to relieving inflammatory reactions, and has important clinical significance.

[0104] The above embodiments of the present invention do not describe all the details in detail, nor limit the present invention to the above embodiments. Various changes, modifications, substitutions and variations made by ordinary technicians in this field without departing from the principles and purpose of the present invention should be included in the protection scope of the present invention.

Claims

1. A medicine for treating hyperuricemia and gout, which is prepared based on Simiao San and using stir-fried Atractylodes macrocephala, Polygonum cuspidatum, Phellodendron chinense, Phellodendron chinense, Coix seeds, Smilax glabra, Curcuma aromatica, Salvia miltiorrhiza, Papaya, Clematidis, Achyranthes bidentata, Tangerine peel and stir-fried White Peony Root as raw materials.

2. The medicine for treating hyperuricemia and gout according to claim 1, wherein the weight portions of each raw material medicine are: stir-fried Atractylodes lancea 10-20, Polygonum cuspidatum 10-20, Psoralea corylifolia 10-30, Phellodendron chinense 10-20, Coix lachryma-jobi 20-50, Smilax glabra 20-50, Curcuma aromatica 10-20, Salvia miltiorrhiza 10-20, Chaenomeles sinensis 10-20, Clematidis 10-20, Achyranthes bidentata 10-20, Tangerine peel 20-50, and stir-fried White Peony Root 10-30.

3. The medicine for treating hyperuricemia and gout according to claim 1, wherein the weight portions of each raw material medicine are: stir-fried Atractylodes lancea 12-18, Polygonum cuspidatum 12-18, Psoralea corylifolia 15-25, Phellodendron chinense 12-18, Coix lachryma-jobi 25-40, Smilax glabra 25-40, Curcuma aromatica 12-18, Salvia miltiorrhiza 12-18, Papaya 12-18, Clematidis 12-18, Achyranthes bidentata 12-18, Tangerine peel 25-40, and stir-fried White Peony Root 15-25.

4. The medicine for treating hyperuricemia and gout according to claim 1, wherein the weight portions of the raw materials are: 15% stir-fried atractylodes, 15% knotweed, 20% euphorbia pulex, 15% salt phellodendron, 30% coix seeds, 30% smilax glabra, 15% turmeric, 15% salvia miltiorrhiza, 15% papaya, 15% clematis, 15% achyranthes bidentata, 30% tangerine peel, and 20% stir-fried white peony root.

5. A method for preparing the drug for treating hyperuricemia and gout according to claim 1, 2, 3 or 4, comprising decocting the raw drug with water, filtering to obtain an extract, and concentrating and drying to obtain the active pharmaceutical ingredient.

6. The method for preparing the drug for treating hyperuricemia and gout according to claim 5, characterized in that The raw material medicine is decocted with water twice, the decoctions are combined, filtered, concentrated and dried to obtain the active pharmaceutical ingredient.

7. The method for preparing the drug for treating hyperuricemia and gout according to claim 6, characterized in that The amount of water used each time is 8 to 12 times the weight of the raw material, and each decoction is 1 to 2 hours.

8. The method for preparing the drug for treating hyperuricemia and gout according to claim 5, characterized in that The extract is concentrated under reduced pressure to form a pharmaceutically active component having a relative density of 1.10 to 1.30 at room temperature.

9. The method for preparing a drug for treating hyperuricemia and gout according to claim 5, characterized in that the active ingredient of the drug is added with a pharmaceutically acceptable excipient or carrier to prepare any conventional oral dosage form.

10. The method for preparing the drug for treating hyperuricemia and gout according to claim 9, characterized in that The oral dosage form is tablet, capsule, granule, pill, mixture, powder, syrup or decoction.

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