A traditional Chinese medicine composition for treating gout and its preparation method and application

Abstract

The invention provides a traditional Chinese medicine composition for treating gout. The composition consists of the following components in parts by weight: 8-12 parts of smilax glabra, 5-9 parts of giant knotweed, 5-9 parts of plantain seeds, 5-9 parts of stir-fried atractylodes with bran, 5-9 parts of phellodendron amurense, 1-4 parts of cyathula, 1-4 parts of coix seed, 1-4 parts of scutellaria baicalensis, 1-4 parts of rhubarb, 1-4 parts of qinpi, 1-4 parts of oldenlandia diffusa, 1-4 parts of cooked rhubarb, 1-4 parts of camara striata, 1-4 parts of saffron vine, 1-4 parts of trachelospermum jasminoides, 1-4 parts of honeysuckle vine, 1-4 parts of safflower, 1-4 parts of boiled peach kernel, 1-4 parts of lithospermum erythrorhizon, 1-4 parts of salvia miltiorrhiza, 1-4 parts of tetrandra stephania tetrandra, and 18-12 parts of roasted astragalus. The Chinese medicinal composition of the present invention has an obvious therapeutic effect on hyperuricemia, can be used to treat gout, and has high safety, no toxic side effects, and good efficacy.

Description

Technical Field

[0001] The present invention relates to the field of traditional Chinese medicine, and in particular to a traditional Chinese medicine composition for treating gout, and a preparation method and application thereof. Background Art

[0002] Gout is a crystalline arthritis caused by purine metabolism disorders and / or decreased uric acid (UA) excretion. It is characterized by the formation of monosodium urate crystals (MSUC) in the synovial fluid and other tissues and often shows significant clinical heterogeneity. Hyperuricemia is the biochemical basis for the onset of gout. Gout is divided into acute gout and chronic gout based on clinical symptoms. Acute gout attacks suddenly and can be induced by trauma, surgery, excessive alcohol consumption, etc., and is characterized by gouty arthritis as the clinical manifestation. Joint redness, swelling, fever, significant tenderness, and limited joint movement seriously affect normal life. Currently, gout is mainly treated with long-term comprehensive treatment of uric acid-lowering and anti-inflammatory analgesic drugs combined with dietary control.

[0003] Currently, colchicine is the primary drug of choice for the treatment of acute gout attacks. However, colchicine is highly toxic and has many adverse reactions, including nausea, vomiting, and diarrhea. Other nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen and diclofenac diethylamide, are used to relieve inflammation in acute gout attacks. After the acute symptoms are relieved, uric acid-lowering drugs are used as adjuncts. However, NSAIDs can also cause numerous complications and adverse reactions, causing significant pain to patients.

[0004] Gout is characterized by recurrent attacks, a long course, and a persistent, difficult-to-cure clinical course. Traditional Chinese medicine (TCM), with its proven efficacy, long-lasting effects, and minimal side effects, is highly effective in treating gout. It demonstrates unique advantages in rapidly improving clinical symptoms, relieving pain, eliminating joint swelling, and relieving localized heat sensations. It also effectively reduces levels of inflammatory markers such as BUA, CRP, and ESR, eliminates tophi, and reduces recurrence rates. Furthermore, TCM, with its vast knowledge base and diverse range of treatments, offers diverse options and synergistic approaches to gout treatment.

[0005] In recent years, the treatment of gout with traditional Chinese medicine has become a research hotspot. Many institutions have been engaged in research on the treatment of gout with traditional Chinese medicine, such as:

[0006] CN111759922B discloses a traditional Chinese medicine composition for treating gout, its preparation method, and use. The composition comprises the following components by weight: 6-12 parts of Chinese Angelica sinensis, 3-10 parts of Chuanxiong rhizome, 15-30 parts of Viola yedoensis, 15-30 parts of Taraxacum mongolicum, 3-9 parts of Summer Melon, 5-12 parts of Achyranthes bidentata, 10-15 parts of Lysimachia chinensis, 3-10 parts of Notopterygium wilfordii, 3-10 parts of Terminalia chebula, and 1-3 parts of Catechu. The composition can relieve the redness, swelling, heat, and pain of acute gout attacks, lower blood uric acid levels, effectively control gout recurrences, and reduce the probability of other complications.

[0007] CN103585561B discloses a traditional Chinese medicine composition for treating gout. The composition is made, by weight, from 5-10 parts of Sophora flavescens, 10-15 parts of Epimedium, 5-10 parts of Aconite, 4-8 parts of Chuanxiong, 8-12 parts of Pyrola, 6-9 parts of Papaya, and 3-6 parts of Amomum villosum. This traditional Chinese medicine composition for treating gout has minimal side effects and exhibits excellent efficacy, with a total clinical efficacy of 96.7%.

[0008] The applicant's patent CN114796392A discloses a Chinese medicine composition for treating gout. The specific formula is: 15-25 parts of mulberry, 15-25 parts of sophora japonica flower, 5-15 parts of polygonatum, 5-15 parts of papaya, 5-15 parts of white hyacinth bean, 5-15 parts of wolfberry, 5-15 parts of yam, 5-15 parts of poria, 10-20 parts of edible herb, 10-20 parts of wormwood stem, 5-15 parts of peach kernel, and 5-15 parts of gardenia. The Chinese medicine composition of the present invention can effectively treat gout, has good efficacy, a short treatment course, and requires a small dosage.

[0009] Although various formulas have been disclosed in the prior art, it is still of great significance to further develop new Chinese medicine compositions that can treat gout. Summary of the Invention

[0010] The purpose of the present invention is to provide a traditional Chinese medicine composition for treating gout, and its preparation method and application. The traditional Chinese medicine composition of the present invention has obvious therapeutic effect on hyperuricemia, can be used for treating gout, and has high safety, no toxic side effects, and good efficacy.

[0011] The technical solution of the present invention is:

[0012] A Chinese medicine composition for treating gout, comprising the following components in parts by weight:

[0013] 8-12 parts of Smilax glabra, 5-9 parts of Polygonum cuspidatum, 5-9 parts of Plantago seed with salt, 5-9 parts of stir-fried Atractylodes lancea with bran, 5-9 parts of Phellodendron amurense, 1-4 parts of Cyathula root, 1-4 parts of Coix seed, 1-4 parts of Herba Cyperi, 1-4 parts of Rhizoma Clerodendrum Smilacis Glabrae, 1-4 parts of Cortex Fragrantis, 1-4 parts of Hedyotis diffusa, 1-4 parts of Rhubarb, 1-4 parts of Caulis Scutellariae, 1-4 parts of Caulis Trachelospermi, 1-4 parts of Caulis Lonicerae, 1-4 parts of Carthamus tinctorius, 1-4 parts of Stewed Peach Kernel, 1-4 parts of Lithospermum erythrorhizon, 1-4 parts of Salvia miltiorrhiza, 1-4 parts of Stephania tetrandra, and 18-12 parts of roasted Astragalus.

[0014] A preferred formula in the embodiment of the present invention is: 10 parts of Smilax glabra, 7 parts of Polygonum cuspidatum, 7 parts of Salt Plantago seed, 7 parts of stir-fried Atractylodes lancea with bran, 7 parts of Phellodendron chinense, 3 parts of Cyathula root, 3 parts of Coix seed, 3 parts of Herba Cyperi coicis, 3 parts of Rhizoma Clerodendrum Smilacis Glabrae, 3 parts of Fraxinus officinalis, 3 parts of Hedyotis diffusa, 7 parts of cooked Rhubarb, 3 parts of Caulis Achyranthis Bidentatae, 3 parts of Caulis Sargentodoxae, 3 parts of Caulis Trachelospermi, 3 parts of Caulis Loniceraes, 3 parts of Carthamus tinctorius, 3 parts of boiled peach kernel, 3 parts of Lithospermum erythrorhizon, 3 parts of Salvia miltiorrhiza, 3 parts of Stephania tetrandra, and 10 parts of roasted Astragalus.

[0015] Another preferred formula in the embodiment of the present invention is: 8 parts of Smilax glabra, 6 parts of Polygonum cuspidatum, 6 parts of Salt Plantago seed, 6 parts of stir-fried Atractylodes lancea with bran, 6 parts of Phellodendron chinense, 2 parts of Cyathula capitata, 2 parts of Coix seed, 2 parts of Coix lacryma-jobi, 2 parts of Rhizoma Cyperi, 2 parts of Scutellaria baicalensis, 2 parts of Fructus Lycopodii, 2 parts of Scutellaria baicalensis, 6 parts of Rhubarb, 2 parts of Caulis Schizonepetae, 2 parts of Caulis Trachelospermi, 2 parts of Caulis Lonicerae, 2 parts of Carthamus tinctorius, 2 parts of Stewed Peach Kernel, 2 parts of Lithospermum erythrorhizon, 2 parts of Salvia miltiorrhiza, 2 parts of Stephania tetrandra, and 9 parts of roasted Astragalus.

[0016] Preferably, the preparation method comprises the following steps: adding water to the above 22 Chinese medicinal materials and decocting them 2-3 times, adding 10-12 times of water each time, and decocting for 1-2 hours; combining the filtrates, concentrating the filtrates under reduced pressure (60-70°C, -0.06-0.08MPa) to a clear paste with a relative density of 1.05-1.10 (60°C), centrifuging, and further concentrating the centrifuge under reduced pressure (60-70°C, -0.06-0.08MPa) to a clear paste with a relative density of 1.20-1.30 (60°C), and vacuum drying (60-70°C, -0.06-0.08MPa) to obtain the Chinese medicine composition.

[0017] More preferably, the Chinese medicine composition is prepared into any one of tablets, granules, capsules, pills, mixtures, decoctions or powders.

[0018] The present invention also provides application of the traditional Chinese medicine composition in preparing medicine for treating gout.

[0019] Prescription of the present invention is explained:

[0020] This disease is often caused by congenital deficiency, dietary imbalances, or pathogenic factors such as wind, cold, dampness, and heat, which lead to the accumulation of dampness in the body, internal accumulation of turbid toxins, which flow into the joints and block the tendons and veins. Damp-heat, phlegm and blood stasis, and turbid toxins are the basic pathologies. Damp-heat stasis, excessive heat and toxins, internal accumulation of phlegm and dampness, and the combination of stasis and heat are the basic pathogenesis. Traditional Chinese Medicine treatment should be based on the principle of "treating the symptoms in an emergency and the root cause in a slow manner," using both attacking and supplementing methods. Treatment focuses on clearing heat and detoxifying, promoting dampness and turbidity, and removing blood stasis and unblocking the meridians, supplemented by invigorating Qi and strengthening the spleen. Main drug: Long-term dietary irregularities, when exposed to factors such as wind, cold, dampness, and heat, can lead to spleen dysfunction, accumulation of dampness and turbid toxins, and internal accumulation of turbid toxins. The Chinese smilax glabra in this recipe is sweet, light, and neutral in nature. It enters the liver and stomach meridians; it removes dampness and toxins, and unclogs the joints. As an important medicine for treating dampness and toxins, "Compendium of Materia Medica" says that Smilax glabra "eliminates dampness and heat, can enter the meridians, and remove the toxins of dampness and heat". Smilax glabra is an important medicine for treating dampness and toxins. "Compendium of Materia Medica" says that "it removes dampness and heat, and benefits the tendons and bones". "The Internal Classic" says that "the so-called dampness harms the skin, flesh, tendons and bones". Moreover, Smilax glabra "eliminates toxins and eliminates evil without hurting the vital energy" ("Bencao Milu"). "Compendium of Materia Medica for Famine Relief" says that it can replace food and has no obvious toxic and side effects when taken in moderation. Therefore, Smilax glabra is used as the main medicine. Astragalus membranaceus replenishes qi and strengthens the exterior, strengthens the body, helps the positive energy to drive out evil, and can promote water circulation and reduce swelling. The two are both main medicines to ensure that the positive energy is not hurt while clearing away dampness and heat toxins.

[0021] Assistant herbs: Polygonum cuspidatum is bitter and cold in nature. It enters the liver, gallbladder, and lung meridians. It dispels wind and dampness, disperses blood stasis, and relieves pain. "Compendium of Materia Medica" states: "It treats wind in the joints and blood stasis." Plantago seed is sweet and slightly cold in nature. It enters the liver, kidney, lung, and small intestine meridians. It clears heat and promotes urination, dissipates dampness, and relieves stranguria. "Medical Compendium" states: "Plantago seed has similar functions to Alisma orientalis, but whereas it specifically removes dampness from the kidneys, it also removes dampness from the spleen." Atractylodes lancea dries dampness and strengthens the spleen, strengthening spleen and stomach function and promoting the excretion of dampness. Phellodendron chinense clears heat and dampness, and when used with Atractylodes lancea, it enhances the effect of clearing damp-heat in the lower jiao. Rhubarb enhances bowel-clearing and heat-relieving, directly eliminating internal heat and toxicity, and promoting the downward movement of damp-heat. These five herbs are assistant herbs, clearing heat, dispersing dampness, and relieving pain, complementing the main herbs.

[0022] Adjuvants: Improper diet impairs the spleen's function, allowing dampness and turbidity to stagnate within the body. Over time, this can transform into heat and stagnate the meridians. Phlegm and dampness block the blood vessels, interacting with the blood to form turbid blood stasis. This stagnation in the meridians or stagnation can transform into heat, leading to internal toxicity. Coix seed enhances the effects of dispelling dampness and heat, and strengthening the tendons and collaterals, effectively treating tendon and bone problems caused by dampness and heat. Cyathula dispels wind and dampness, unblocking the joints. These two herbs work synergistically to enhance dampness removal and collateral unblocking. Herba Corydalis dispels turbidity and toxins, unblocking the joints and effectively treating back pain and rheumatic pain. Rhizoma Smilacis Glabrae dispels wind and activates the collaterals, promoting diuresis and dredging the menstrual cycle. Cortex Fraxini and Herba Hedyotis Dichroae clear heat, detoxify, and dry out dampness. Cortex Fraxini can also gather scattered vital energy, while Herba Hedyotis Dichroae can also invigorate blood circulation, promote urination, and relieve inflammation and pain. These herbs complement each other in treating damp-heat stagnation and excessive heat and toxicity. The Compendium of Materia Medica states, "All vines can open the meridians and collaterals." Vine herbs can penetrate deep into the meridians and channels, searching for and dislodging trapped external or internal wind pathogens. Once the wind pathogens are dispelled, the meridians are unblocked, allowing for smooth flow of qi and blood. Stem vines are thick and heavy in texture, excelling at dispelling blood stasis in deep meridian channels. Their shape resembles tendons, making them particularly effective in treating tendon disorders. Their combined strength and flexibility allow them to bend and stretch, softening and relaxing tendons. Therefore, adjuvant herbs such as Caulis Aconiti Lateralis Preparata, Caulis Trachelospermi Caulis, and Caulis Lonicera Japonica are used to dispel wind and dampness, activate blood circulation, and unclog the meridians. Vine herbs can also guide the treatment to the affected area. Dampness accumulates into phlegm, and accumulation of phlegm and dampness can lead to qi stagnation and blood stasis. If gout persists for years, "long-term illness leads to blood stasis." Therefore, safflower, peach kernel, lithospermum officinale, and salvia miltiorrhiza are used to activate blood circulation, dispel blood stasis, and relieve pain. Stephania tetrandra dispels wind and promotes diuresis, enhancing the treatment of rheumatic pain. These herbs are all adjuvant herbs.

[0023] The above herbs are combined to simultaneously tonify and purge, lift and descend, and warm and clear. This approach tonifies Qi without stoking internal heat, eliminates pathogenic factors without damaging body fluids, supports the body's health without clinging to them, and detoxifies without harming the body's health. It effectively clears away heat and toxins, dissipates dampness and turbidity, resolves blood stasis and dredges the meridians, and invigorates Qi and strengthens the spleen. The entire formula demonstrates rigorous composition and appropriate compatibility, and its clinical efficacy is undeniable.

[0024] The effects of each Chinese medicine are as follows:

[0025] Smilax glabra: Sweet, mild, and neutral. It enters the Liver and Stomach meridians. It detoxifies, removes dampness, and promotes joint function. It is used to treat syphilis, mercury poisoning, fire-induced carbuncles, stranguria caused by heat, and painful, red, and astringent urination.

[0026] Polygonum cuspidatum: Bitter and cold. It enters the liver, gallbladder, and lung meridians. It clears heat and detoxifies, promotes dampness and reduces jaundice, and promotes blood circulation and relieves pain. It is used to treat damp-heat jaundice, carbuncles, sores, injuries from falls, and blood stasis and amenorrhea.

[0027] Salt Plantago Seed: Sweet, salty, and cold. It enters the kidney, bladder, and lung meridians. It has diuretic and stranguria-relieving properties, clears heat and dampness, and improves eyesight. It is used to treat dysuria, stranguria, red and swollen eyes, and cough with sputum.

[0028] Stir-fried Atractylodes lancea with bran: Pungent, bitter, and warm. It enters the spleen and stomach meridians. It clears dampness and strengthens the spleen, induces sweating and relieves exterior symptoms, and improves eyesight. It is used to treat dampness in the middle jiao, abdominal distension, rheumatic pain, and night blindness.

[0029] Phellodendron chinense: Bitter and cold. Enters the kidney, bladder, and large intestine meridians. Clears heat and dampness, purges fire and detoxifies. Used for damp-heat syndrome, jaundice, hemorrhoids, and sore throat.

[0030] Rhizoma Cynanchifolia: Sweet, slightly bitter, neutral. Enters the Liver and Kidney meridians. Benefits: activating blood circulation, tonifying the liver and kidneys, strengthening tendons and bones, and promoting urination and relieving stranguria. Used for amenorrhea, dysmenorrhea, soreness of the waist and knees, traumatic injuries, and stranguria.

[0031] Coix seed: Sweet, light, and slightly cold. It enters the spleen, lung, and kidney meridians. It strengthens the spleen, dispels dampness, relieves numbness and stops diarrhea, and clears heat and discharges pus. It is used to treat spleen deficiency, dampness, edema, beriberi, and lung abscesses.

[0032] Herba Dioscoreae: Bitter, neutral. Enters the kidney and bladder meridians. Effective for dispelling dampness, removing turbidity, and dispelling wind and dampness. Used for stranguria, leucorrhea, and rheumatic pain.

[0033] Rhizoma Lulutong: Bitter, neutral. Enters the Liver and Stomach meridians. Benefits: activating blood circulation, promoting lactation, and promoting diuresis and reducing swelling. Used for postpartum milk retention, rheumatic pain, and edema.

[0034] Qinpi: Bitter and cold. Enters the Liver, Gallbladder, and Large Intestine meridians. Clears heat and dampness, cools blood and stops bleeding, and improves eyesight. Used for damp-heat diarrhea, red and swollen eyes, and bloody diarrhea.

[0035] Hedyotis diffusa: Bitter, sweet, and cold. It enters the Heart, Liver, and Stomach meridians. It clears heat and detoxifies, promotes dampness and relieves stranguria. It is used to treat sores, damp-heat jaundice, and painful and dribbling urination.

[0036] Cooked Rhubarb: Bitter and cold. It enters the spleen, stomach, large intestine, liver, and heart meridians. It clears heat and promotes bowel movements, cools the blood and detoxifies, and removes blood stasis and promotes menstruation. It is used for constipation caused by excess heat, bleeding caused by blood heat, and amenorrhea.

[0037] Cistanche deserticola: Bitter and slightly cold. It enters the liver, spleen, and kidney meridians. It strengthens the spleen and aids digestion, clears heat and detoxifies, and relieves pain. It is used to treat abdominal distension caused by food accumulation, malnutrition in children, and abdominal pain caused by diarrhea.

[0038] Sargentodoxae: Bitter, neutral. Enters the Liver and Large Intestine meridians. Benefits: activating blood circulation, clearing away heat and detoxifying, and relieving swelling and pain. Used for traumatic injuries, dysmenorrhea, and rheumatic pain.

[0039] Trachelospermum officinale: Bitter and slightly cold. Enters the Liver and Kidney meridians. It dispels wind, dredges the meridians, cools blood, and reduces swelling. It is used for rheumatic fever, joint swelling, heat, and pain, and sore throat.

[0040] Honeysuckle Vine: Sweet, cold. Enters the Lung, Heart, and Stomach meridians. Clears heat and detoxifies, dispels wind and unclogs the meridians. Used for wind-heat colds, fevers caused by febrile diseases, sores, boils, and swellings.

[0041] Safflower: Pungent and warm. It enters the Heart and Liver meridians. It promotes blood circulation, promotes menstruation, dissipates blood stasis, and relieves pain. It is used for treating blood stasis, amenorrhea, postpartum lochia retention, and chest pain.

[0042] Stewed peach kernel: Bitter, sweet, neutral. Entries the Heart, Liver, and Large Intestine meridians. Benefits: Activates blood circulation, removes blood stasis, moistens the intestines, and promotes bowel movements. Used for symptoms of blood stasis, dry bowels, and constipation.

[0043] Lithospermum officinale: Bitter, sweet, and cold. It enters the Heart and Liver meridians. It cools the blood, invigorates blood circulation, detoxifies, and clears rashes. It is used to treat purple-black macules, measles that haven't cleared up, and sores and swelling.

[0044] Salvia miltiorrhiza: Bitter, slightly cold. Enters the Heart and Liver meridians. Benefits: activating blood circulation, removing blood stasis, relieving menstrual pain, clearing the heart and relieving restlessness, cooling blood and eliminating carbuncle. Used for chest pain, irregular menstruation, and sores, swelling, and pain.

[0045] Stephania tetrandra: Bitter, pungent, and cold. It enters the bladder, kidney, and spleen meridians. It promotes diuresis and reduces swelling, dispels wind and relieves pain, and clears heat and detoxifies. It is used for edema, rheumatic pain, eczema, and sores.

[0046] Roasted Astragalus: Sweet, slightly warm. Enters the Lung and Spleen meridians. Benefits: tonifying Qi and raising Yang, strengthening the exterior and stopping sweating, promoting diuresis and reducing swelling, promoting fluid production and nourishing blood. It is used for Qi deficiency, fatigue, poor appetite, loose stools, spontaneous sweating due to exterior deficiency, and fatigue caused by internal injuries.

[0047] Compared with the prior art, the advantages of the present invention are:

[0048] 1. Pharmacodynamic study data show that by replicating a hyperuricemia rat model, the Chinese medicine composition of the present invention has a significant therapeutic effect on hyperuricemia, can significantly reduce the levels of CREA and UREA in rats, reduce the urine uric acid level and the kidney organ coefficient, and have a significant repair effect on pathological changes in the kidneys; by replicating a gout model rat, the Chinese medicine composition of the present invention has the effect of reducing the joint swelling of acute gout model rats.

[0049] 2. The repeated administration toxicity test and single administration toxicity test of the Chinese medicine composition of the present invention in rats by oral gavage for 3 months showed that the Chinese medicine composition of the present invention is highly safe and has no toxic side effects.

[0050] 3. The preparation method of the Chinese medicine composition of the present invention is simple, the clinical experimental effect is high, and there is no adverse reaction and high safety.

[0051] 4. Compared with the formula of the comparative example, the synergistic effect between the drugs in the Chinese medicine composition of the present invention is stronger and has better therapeutic effect.

[0052] The detailed structure of the present invention is further described below in conjunction with the accompanying drawings and specific embodiments. BRIEF DESCRIPTION OF THE DRAWINGS

[0053] Figure 1 The diagram is a macroscopic observation diagram of rat kidney tissue; Note: A: blank control group, B: model control group, C: comparative example 1, D: comparative example 2, E: example 1, F: allopurinol tablet group.

[0054] Figure 2 This is a histopathological image of rat kidneys (HE, ×200); Note: A blank control group, B model control group, C comparative example 1, D comparative example 2, E example 1, F allopurinol tablets group. In the blank control group, the renal cortex and medulla structure were clear, the morphology and structure of the renal units were normal, and no inflammatory cell infiltration was observed in the interstitium; in the model control group, the basophilia of the renal tubular epithelium was enhanced and flattened, the lumen was dilated, the renal tubular epithelial cells were necrotic and accompanied by granulomatous lesions, fibrous connective tissue proliferation in the interstitium, and inflammatory cell infiltration was observed in the renal tubular lumen and interstitium; in the comparative example 1 group, the basophilia of the renal tubular epithelium was enhanced and flattened, the lumen was dilated, the renal tubular epithelial cells were necrotic and accompanied by Granuloma-like lesions, with a small amount of inflammatory cell infiltration in the interstitium; in the comparative example 2 kidney, multifocal renal tubular epithelial basophilia was enhanced and flattened, the tubular lumen was dilated, the tubular epithelial cells were necrotic and accompanied by granuloma-like lesions, and fibrous connective tissue proliferation in the interstitium; in the example 1 kidney, multifocal renal tubular epithelial basophilia was enhanced and flattened, the tubular lumen was dilated, and a small amount of inflammatory cell infiltration was visible in the tubular lumen; in the allopurinol tablets group, multifocal renal tubular epithelial basophilia was enhanced, the tubular lumen was dilated, and the tubular epithelial cells were necrotic.

[0055] Figure 3 Figure 2 is a histopathological image of rat liver (HE, ×200); Note: A: blank control group, B: model control group, C: comparative example 1, D: comparative example 2, E: example 1, F: allopurinol tablet group. Hepatocyte cords in each group were orderly arranged, with no degeneration or necrosis of hepatocytes, and no congestion of the hepatic sinusoids.

[0056] Figure 4 It is the histopathological picture of rat synovium (HE, ×200), note: A blank control group, B model control group, C comparative example 1, D comparative example 2, E example 1, F Tongfengding capsule group. In the blank control group, no pathological changes such as proliferation and hypertrophy of lining cells, hyperplasia of fibrous connective tissue, and hyperplasia of granulation tissue, vascular tissue growth, and inflammatory cell infiltration were observed in the subsynovial tissue; in the model control group, hyperplasia and hypertrophy of lining cells of synovial tissue, hyperplasia of fibrous tissue, hyperplasia of granulation tissue of subsynovial tissue, vascular tissue growth, a large number of inflammatory cells infiltrated, and a large amount of necrotic tissue were observed; in comparative example 1, hyperplasia and hypertrophy of lining cells of synovial tissue, hyperplasia of fibrous tissue, hyperplasia of granulation tissue of subsynovial tissue, vascular tissue growth, and a large number of inflammatory cells infiltrated were observed; in comparative example 2, hyperplasia and hypertrophy of lining cells of synovial tissue, hyperplasia of fibrous tissue, hyperplasia of granulation tissue of subsynovial tissue, vascular tissue growth, and a large number of inflammatory cells infiltrated were observed; in example 1, hypertrophy of lining cells of synovial tissue, hyperplasia of fibrous tissue, and a small amount of inflammatory cell infiltration of subsynovial tissue were observed; in the Tongfengding capsule group, hypertrophy of lining cells of synovial tissue, hyperplasia of fibrous tissue, and a small amount of inflammatory cell infiltration of subsynovial tissue were observed. DETAILED DESCRIPTION

[0057] Example 1

[0058] A traditional Chinese medicine composition for treating gout is composed of the following components by weight: 10 parts of Smilax glabra, 7 parts of Polygonum cuspidatum, 7 parts of Plantago seed, 7 parts of stir-fried Atractylodes lancea with bran, 7 parts of Phellodendron amurense, 3 parts of Cyathula root, 3 parts of Coix seed, 3 parts of Herba Dichroae, 3 parts of Fructus Smilacis Glabrae, 3 parts of Cortex Fraxini, 3 parts of Hedyotis diffusa, 7 parts of Rhubarb, 3 parts of Caulis Scutellariae, 3 parts of Sargentodoxae, 3 parts of Trachelospermi Caulis, 3 parts of Caulis Loniceraes, 3 parts of Carthamus tinctorius, 3 parts of boiled peach kernel, 3 parts of Lithospermum erythrorhizon, 3 parts of Salvia miltiorrhiza, 3 parts of Stephania tetrandra, and 10 parts of roasted Astragalus.

[0059] Preparation method: The above 22 Chinese medicinal materials are decocted twice with water, the first time with 12 times the amount of water and decocted for 2 hours; the second time with 10 times the amount of water and decocted for 1 hour, the filtrates are combined, the filtrates are concentrated under reduced pressure (60-70°C, -0.06-0.08MPa) to a clear paste with a relative density of 1.05-1.10 (60°C), centrifuged, and the centrifugedate is further concentrated under reduced pressure (60-70°C, -0.06-0.08MPa) to a clear paste with a relative density of 1.20-1.30 (60°C), vacuum dried (60-70°C, -0.06-0.08MPa) to obtain a dry paste, and the Chinese medicine composition of the present invention is obtained.

[0060] Further, add appropriate amount of dextrin, crush into fine powder, mix evenly, granulate, dry, granulate, mix the whole, make into 1000g, and pack it inside to obtain the product.

[0061] Table 1 Detailed description of the particle preparation process

[0062]

[0063]

[0064] Comparative Example 1

[0065] A traditional Chinese medicine composition is composed of the following components by weight: 10 parts of Rhizoma Smilacis Glabrae, 7 parts of Polygonum Cuspidati, 7 parts of Rhizoma Atractylodis Macrocephalae with bran, 7 parts of Phellodendron amurense, 3 parts of Cyathula officinalis, 3 parts of Semen Coicis, 3 parts of Herba Dichroae, 3 parts of Hedyotis diffusa, and 3 parts of Caulis Loniceraes. The specific preparation process is the same as that in Example 1.

[0066] Comparative Example 2

[0067] A traditional Chinese medicine composition, comprising the following components by weight: 10 parts of rhizoma smilacis gracile, 7 parts of polygonum cuspidatum, 7 parts of plantain seeds, 7 parts of stir-fried atractylodes lancea with bran, 7 parts of phellodendron amurense, 3 parts of cyathula root, 3 parts of coix seed, 3 parts of scutellaria baicalensis, 3 parts of liquidambar formosana, 3 parts of qinpi bark, 3 parts of oldenlandia diffusa, 7 parts of cooked rhubarb, 3 parts of scutellaria baicalensis, 3 parts of safflower caulis, 3 parts of trachelospermum officinale, and 3 parts of honeysuckle caulis. The specific preparation process is the same as that in Example 1.

[0068] Example 2 Single-dose toxicity test of rats orally administered the Chinese medicine composition pills prepared in Example 1

[0069] Objective: In this study, SD rats were orally administered the Chinese medicine composition prepared in Example 1 twice within 24 hours and observed for 14 consecutive days. The results of the acute toxicity test on SD rats were used to understand the extent of toxic reactions and the organs involved, so as to provide a basis for the dose design and selection of toxicity reaction indicators for repeated administration toxicity tests.

[0070] Experimental method: 40 SPF-grade SD rats (half male and half female) weighing 180.5-205.2g were selected and raised in 475mm×350mm×200mm cages, 5 rats per cage. The rats were raised according to the international (GB14925-2010) SPF-grade laboratory animal environmental conditions. The experimental animals were quarantined and acclimated for 6 days. They were randomly divided into two groups according to their body weight: a blank control group and a Chinese medicine composition group prepared in Example 1 (143.6g crude drug / kg), with 20 rats in each group. Before the experiment, the rats were fasted for more than 12 hours but not water. Then, they were orally gavaged with pure water and the Chinese medicine composition prepared in Example 1 at 20mL / kg. The rats were administered twice on the day of administration. Within 0-4 hours after each administration, the poisoning symptoms and characteristics, the occurrence of toxic reactions and the recovery time, as well as the death of the experimental animals in each group were closely observed and recorded. The rats were then observed twice a day, once in the morning and once in the afternoon, for 14 consecutive days. The experimental animals were weighed before administration on the day of administration and on the 4th, 7th, 10th and 14th days after administration, and the weight changes of the experimental animals were recorded.

[0071] Experimental Results: 1) Effects on General Activity, Poisoning Symptoms, and Mortality in Experimental Animals: 1 hour 56 minutes to 3 hours 29 minutes after the first administration, 7 / 20 rats in the group receiving the Chinese herbal composition prepared in Example 1 developed loose stools. None of the rats that developed loose stools recovered during the 4-hour observation period. 30 minutes to 57 minutes after the second administration, an additional 1 / 4 of the rats in the group receiving the Chinese herbal composition prepared in Example 1 developed loose stools. 2 hours 18 minutes to 3 hours 30 minutes after the second administration, 13 / 20 rats in the group receiving the Chinese herbal composition prepared in Example 1 developed loose yellow-brown stools. 2F05 continued to experience loose stools the next morning, but recovered in the afternoon. The remaining rats that developed loose stools all recovered the next morning. No other toxic reactions or animal deaths were observed. Observation continued for 14 days after administration. No significant abnormalities in behavior, mental state, or diet were observed in the blank control group or the group receiving the Chinese herbal composition prepared in Example 1. No toxic reactions or animal deaths were observed.

[0072] 2) Effect on Body Weight: The experimental animals were weighed before dosing on the day of administration, and on days 4, 7, 10, and 14 after administration. Compared to the blank control group during the same period, no statistically significant difference in body weight was observed in the group receiving the Chinese medicine composition prepared in Example 1, and weight gain was within the normal range. These results indicate that under the experimental conditions, oral administration of the Chinese medicine composition prepared in Example 1 twice to rats had no significant effect on their body weight. See Appendix Tables 1, 2, and 3 for details.

[0073] 3) At the end of the experiment, gross anatomy of SD rats was observed with the naked eye: no obvious abnormalities were found on the surface and cross-section of any organ.

[0074] Result calculation and statistics

[0075] The data were rounded off to the nearest integer. SPSS 16.0 was used for statistical analysis, and the weights were expressed as mean ± standard deviation. The t-test was used for comparison between the two groups when the data met the requirements of normality and homogeneity of variance. The Mann-Whitney Test was used when the data did not meet the requirements of normality or homogeneity of variance. P < 0.05 indicated statistical significance, and P < 0.01 indicated that the difference was highly significant.

[0076] Conclusion: Under the experimental conditions, rats were orally administered the Chinese medicine composition prepared in Example 1 at a volume of 20 mL / kg, twice a day, with a cumulative dose of 143.6 g crude drug / kg, equivalent to 95 times the intended clinical dosage per kilogram of body weight for adults (the daily dose for adults is 1.514 g crude drug / kg). No obvious toxic reactions or deaths were observed in the experimental animals.

[0077] Table 2 Effect of the Chinese medicine composition prepared in Example 1 on the body weight of SD rats (n=20, )

[0078]

[0079] Table 3 Effects of the Chinese medicine composition prepared in Example 1 on the body weight of female SD rats (n=10, )

[0080]

[0081] Table 4 Effects of the Chinese medicine composition prepared in Example 1 on the body weight of male SD rats (n=10, )

[0082]

[0083] Example 3 Toxicity test of rats after oral administration of the Chinese medicine combination prepared in Example 1 for 3 months

[0084] Objective: This study was conducted in accordance with the national GLP standards to observe the repeated administration toxicity test of the Chinese medicine combination prepared in Example 1 in SD rats after oral administration of different doses, evaluate the toxicity of the Chinese medicine combination prepared in Example 1 after repeated administration to SD rats, and provide reference data for the clinical use of the Chinese medicine combination prepared in Example 1.

[0085] Methods: 120 SD rats that passed quarantine were selected, half male and half female, weighing 180.1-218.1 g, and measuring 475×350×200 mm. 3 The animals were kept in cages, with 5 rats per cage. The experimental animals were quarantined and acclimatized for 5 days. They were randomly divided into 4 groups according to sex and weight, namely the blank control group, the low-dose, medium-dose and high-dose groups of the Chinese medicine combination prepared in Example 1 (the daily cumulative doses were 27.0, 53.7 and 107.7 g crude drug / kg, respectively), 30 rats in each group, and administered orally twice a day at a volume of 15 mL / kg for 3 consecutive months (13 weeks). At the end of the administration period (the 13th week) and the end of the recovery period (the 17th week), 20 and 10 rats were dissected in each group, half male and half female, respectively, as planned. The examination items include: general clinical observation; body weight and food intake measurement; ophthalmological examination; urine examination; hematology, blood biochemistry, electrolytes, coagulation, organ coefficient measurement; histopathological examination.

[0086] Results: During the experiment, all experimental animals were euthanized as planned, and no experimental animals died abnormally during the experiment.

[0087] General clinical observation: During the dosing period and the recovery period, the appearance, physical signs, behavioral activities and general conditions of the experimental animals in each dosage group of the Chinese medicine combination prepared in Example 1 were compared with the blank control group during the same period, and no abnormalities related to drug toxicity were found.

[0088] Body weight: During the test period, the body weight of each dosage group of the Chinese medicine combination prepared in Example 1 was compared with that of the blank control group during the same period, and no toxicological changes were observed. The results showed that the Chinese medicine combination prepared in Example 1 had no significant effect on the body weight of rats.

[0089] Food intake: During the test period, the average food intake of each dosage group of the Chinese medicine combination prepared in Example 1 was compared with that of the blank control group during the same period, and no toxicological changes were observed. The results showed that the Chinese medicine combination prepared in Example 1 had no significant effect on the food intake of rats.

[0090] Hematological examination: When the hematological indices of each dosage group of the Chinese medicine combination prepared in Example 1 were compared with those of the blank control group during the same period, no toxicologically significant changes were observed. The results showed that the Chinese medicine combination prepared in Example 1 had no significant effect on the hematological indices of rats.

[0091] Blood biochemical examination: The blood biochemical indices of each dosage group of the Chinese medicine combination prepared in Example 1 were compared with those of the blank control group during the same period. No toxicologically significant changes were observed. The results showed that the Chinese medicine combination prepared in Example 1 had no significant effect on the blood biochemical indices of rats.

[0092] Coagulation test: The coagulation indexes of each dosage group of the Chinese medicine combination prepared in Example 1 were compared with those of the blank control group during the same period. No toxicologically significant changes were observed. The results showed that the Chinese medicine combination prepared in Example 1 had no significant effect on the coagulation indexes of rats.

[0093] Electrolyte examination: The electrolyte indices of each dosage group of the Chinese medicine combination prepared in Example 1 were compared with those of the blank control group during the same period, and no toxicologically significant changes were observed. The results showed that the Chinese medicine combination prepared in Example 1 had no significant effect on the electrolyte indices of rats.

[0094] Routine urine examination: When the urine indices of each dosage group of the Chinese medicine combination prepared in Example 1 were compared with those of the blank control group during the same period, no toxicologically significant changes were observed. The results showed that the Chinese medicine combination prepared in Example 1 had no significant effect on the urine indices of rats.

[0095] Ophthalmological examination: During the test period, no obvious abnormalities were found in the ophthalmological examinations of the various dosage groups of the Chinese medicine combination prepared in Example 1 and the blank control group.

[0096] Organ coefficients: Compared with the blank control group during the same period, no toxicologically significant changes were observed in the organ coefficients of the Chinese medicine combination prepared in Example 1 at each dose group. The results showed that the Chinese medicine combination prepared in Example 1 had no significant effect on the organ coefficients of rats.

[0097] Gross anatomy and pathological examination: Gross observation and microscopic observation showed no obvious pathological changes in the experimental animals dissected at the end of the drug administration period and the end of the recovery period.

[0098] Conclusion: Under the conditions of this experiment, SD rats were orally administered the Chinese medicine combination prepared in Example 1 for 3 months with no apparent drug-related toxicity (NOAEL) of 107.7 g crude drug / kg (equivalent to 71 times the intended clinical dose for a 70 kg adult and 11.3 times the equivalent dose).

[0099] Table 5 Effect of the Chinese herbal medicine combination prepared in Example 1 on the body weight of animals (g, )

[0100]

[0101]

[0102] Note: Compared with the blank control group, there was no statistical difference in each dosage group of the Chinese medicine combination prepared in Example 1.

[0103] Table 6 Effect of the Chinese herbal medicine combination prepared in Example 1 on the average food intake of animals (g / animal / day, )

[0104]

[0105] Note: Compared with the blank control group, there was no statistical difference in each dosage group of the Chinese medicine combination prepared in Example 1.

[0106] Table 7 Effect of the Chinese herbal combination prepared in Example 1 on animal hematology

[0107]

[0108]

[0109] Note: Compared with the blank control group, * P<0.05, ** P<0.01.

[0110] Table 8 Effect of the Chinese medicine combination prepared in Example 1 on animal blood biochemical indicators

[0111]

[0112]

[0113] Note: Compared with the blank control group, * P<0.05, ** P<0.01.

[0114] Table 9 Effect of the Chinese herbal combination prepared in Example 1 on animal coagulation

[0115]

[0116] Note: Compared with the blank control group, there was no statistical difference in each dosage group of the Chinese medicine combination prepared in Example 1.

[0117] Table 10 Effect of the Chinese medicine combination prepared in Example 1 on animal electrolytes

[0118]

[0119] Note: Compared with the blank control group, * P<0.05, ** P<0.01.

[0120] Table 11 Effects of the Chinese herbal combination prepared in Example 1 on animal urine indicators

[0121]

[0122]

[0123] Note: Compared with the blank control group, * P<0.05.

[0124] Table 12 Statistics of the effect of the Chinese medicine combination prepared in Example 1 on animal organ coefficients ( mg / g)

[0125]

[0126] Note: Compared with the blank control group, * P<0.05, ** P<0.01.

[0127] Example 4 Pharmacodynamic study data of the formula of Example 1

[0128] Experiment 1 Effect of the formula of Example 1 on hyperuricemia model rats

[0129] 1. Purpose of the study

[0130] This experiment replicated a hyperuricemia rat model to investigate the therapeutic effect of the formula of Example 1 on hyperuricemia, providing an experimental basis for the clinical application of the formula of Example 1.

[0131] 2.1 Test materials

[0132] Test substance (test sample): Chinese medicine composition of Example 1 and Comparative Example 1 and Comparative Example 2 (Guyitang (Hunan) Health Technology Co., Ltd.), 1g dry paste contains 8.545g crude drug, ointment, clinical dosage: 106g crude drug / day; clinical route: oral, clinical course of treatment: 1 month

[0133] Positive control drug: Name: Allopurinol tablets, Specification: 0.1g*100 tablets, Manufacturer: Hefei Jiulian Pharmaceutical Co., Ltd., Usage and Dosage: Oral. Adults: 0.5-1 tablet at a time, 1-2 times a day

[0134] Experimental animals: 60 SPF-grade SD male rats, weight range: 195.1-214.4 g; (Hunan Slake Jingda Experimental Animal Co., Ltd.)

[0135] 3. Test methods

[0136] 3.1 Model construction and drug administration

[0137] 60 male SD rats that have passed the quarantine test were randomly divided into a blank control group, a model control group, an embodiment 1 group, a comparative example 1 group, a comparative example 2 group, and an allopurinol tablets group according to body weight, with 10 rats in each group. The blank control group was gavaged with 0.1% CMC-Na solution. All the other groups of rats were gavaged with 10 mL / kg of potassium oxonate (400 mg / kg) and adenine (0.1 g / kg) suspension (potassium oxonate and adenine were dissolved in 0.1% CMC-Na and made into suspension), and the modeling drugs were gavaged every morning. Every afternoon, each drug group was gavaged with the corresponding dose of drugs at 15 mL / kg, and the blank control group and the model control group were gavaged with equal volumes of pure water, and the modeling and administration were continued for 3 weeks.

[0138] 3.2 Test and control article dosage design

[0139] The proposed clinical dosage of the Chinese herbal composition of Example 1 and Comparative Examples 1 and 2 is 106 g of crude drug per day. The rat equivalent dose, calculated based on body surface area, is: 106 g of crude drug per day × 0.018 ÷ 0.2 kg = 9.54 g of crude drug per kg. The dosage of the allopurinol tablet group was set at 0.02 g / kg based on the literature. A blank control group and a model control group were also established, as detailed in Table 13.

[0140] Table 13 Dosage design for each group

[0141]

[0142] Note: 1g dry paste powder is equivalent to 8.545g crude drug.

[0143] 3.3 Drug preparation:

[0144] The Chinese medicine composition of Example 1 and Comparative Examples 1 and 2: Weigh 4.44 g of the dry paste powder of the Chinese medicine composition of Example 1 and Comparative Examples 1 and 2, and add purified water to 60 mL (0.074 g dry paste powder / mL);

[0145] Allopurinol tablet group: grind one allopurinol tablet (0.1 g), add purified water to make up to 100 mL (0.001 g / mL);

[0146] The preparation volume was adjusted according to the weekly changes in rat body weight.

[0147] 3.4 Detection indicators

[0148] 1. General observation: After modeling and drug administration, closely observe and record the appearance, behavior, secretions, excretions, diet, etc. of each group of experimental animals. If the experimental animals are found dead or dying, they should be dissected and observed in time. Weigh the experimental animals weekly;

[0149] 2. One day before the last administration, 24-hour urine of rats in each group was collected using metabolic cages to measure the urine uric acid content;

[0150] 3. After the last administration, blood was collected from the abdominal aorta to determine the levels of uric acid, creatinine (CREA), urea nitrogen (BUN) and xanthine oxidase (XOD) in the rat serum;

[0151] 4. Remove the liver and kidneys of the rats, weigh their wet weight and calculate their organ index, organ index = organ wet weight (mg) / rat body weight (g);

[0152] 5. Histopathological examination: Histopathological examination was performed on the kidneys and livers of rats. The evaluation indexes and scoring criteria of kidney histopathology are shown in Table 14.

[0153] Table 14 Renal histopathology evaluation indicators and scoring criteria

[0154]

[0155]

[0156] 3.5 Result calculation and statistics

[0157] SPSS 16.0 software was used for data statistics, and the measurement data were expressed as mean ± standard deviation. For comparisons between multiple groups, normality and homogeneity of variance were first compared. When the variances were homogeneous and normal, one-way analysis of variance was used. When normality was not met, the non-parametric T test was used. When normality was met but the variances were not homogeneous, the Tamhane's T2 test was used. If normality was not met, the Kruskal-Wallis test was used, and pairwise comparisons were performed using the Mann-Whitney test. P < 0.05 indicated a statistically significant difference, and P < 0.01 indicated a statistically significant difference. Biological significance was considered in the evaluation.

[0158] 4. Experimental Results

[0159] 4.1 Effects on CREA and UREA Levels in Rats

[0160] Compared with the blank control group, the serum CREA and UREA levels of the rats in the model control group were significantly increased (P < 0.01), indicating that the model was successfully established; compared with the model control group, the serum CREA and UREA levels of each administration group were significantly or significantly reduced (P < 0.05 or P < 0.01), compared with comparative example 1, comparative example 2 had a downward trend, but no statistical difference was seen, compared with comparative example 1, the serum CREA and UREA levels of Example 1 were significantly reduced (P < 0.01), compared with comparative example 2, the serum CREA and UREA levels of Example 1 were significantly reduced (P < 0.05), compared with the allopurinol tablets group, there was a downward trend for Example 1, but no statistical difference was seen. CREA and UREA are both important indicators for clinical detection of renal function, and elevated levels suggest possible renal impairment. The results show that the granules of Example 1 have a significant therapeutic effect on hyperuricemia model rats. The results are shown in Table 15.

[0161] Table 15 Effects of each group on the levels of CREA and UREA in rats ( n=10)

[0162]

[0163] Note: Compared with the blank control group, "**" indicates P < 0.01, compared with the model control group, " Δ " indicates P < 0.05," ΔΔ ” indicates P < 0.01, “▲▲” indicates P < 0.01 compared with Comparative Example 1, and “#” indicates P < 0.05 compared with Comparative Example 2.

[0164] 4.2 Effects on serum uric acid and urine uric acid levels in rats

[0165] Compared with the blank control group, the serum uric acid level of the rats in the model control group was significantly increased (P < 0.01), and the urine uric acid level was significantly reduced (P < 0.01); compared with the serum UA of the model control group, the serum uric acid of the allopurinol tablets group was significantly reduced, and the serum uric acid of the remaining groups had a downward trend. Example 1 had a downward trend relative to Comparative Example 1 and Comparative Example 2, but no statistical difference was found. Compared with the model control group, the urine UA levels of Comparative Example 2, Example 1 and the allopurinol tablets group were significantly or significantly increased (P < 0.05 or P < 0.01), the urine UA level of Comparative Example 1 increased, but no statistical difference was found, the urine UA level of Comparative Example 2 increased compared with Comparative Example 1, but no statistical difference was found, the urine UA level of Example 1 was significantly increased compared with Comparative Example 1 (P < 0.05), the urine UA level of Example 1 increased compared with Comparative Example 2, but no statistical difference was found, and the urine UA level of Example 1 increased compared with the allopurinol tablets group, but no statistical difference was found. The results showed that the granules of Example 1 had a tendency to reduce the serum uric acid level in hyperuricemia model rats and promoted the excretion of uric acid in the model rats. The results are shown in Table 16.

[0166] Table 16 Effects of each group on UA ​​levels in rats ( n=10)

[0167]

[0168] Note: Compared with the blank control group, "**" indicates P < 0.01, compared with the model control group, " Δ " indicates P < 0.05; " ΔΔ ” indicates P < 0.01, and “▲” indicates P < 0.05 compared with Comparative Example 1.

[0169] 4.3 Effects on rat liver and kidney organ coefficients

[0170] Compared with the blank control group, the kidney organ coefficient of the model control group rats significantly increased (P < 0.01); Compared with the model control group, the kidney organ coefficient of each administration group was significantly or significantly reduced (P < 0.05 or P < 0.01), compared with comparative example 1, comparative example 2 had a downward trend, but no statistical difference was seen, compared with comparative example 1, embodiment 1 had a downward trend (P < 0.05), compared with comparative example 2, embodiment 1 had a downward trend (P < 0.05), compared with the allopurinol tablets group, embodiment 1 had a downward trend, but no statistical difference was seen. Each administration group had no significant effect on the liver organ coefficient. The results show that the granules of embodiment 1 can reduce the kidney coefficient of hyperuricemia model rats. The results are shown in Table 17.

[0171] Table 17 Effects of each group on the liver and kidney organ coefficients of rats ( n=10)

[0172]

[0173]

[0174] Note: Compared with the blank control group, "**" indicates P < 0.01, compared with the model control group, " Δ " indicates P < 0.05," ΔΔ ” indicates P < 0.01, “▲” indicates P < 0.05 compared with Comparative Example 1, and “#” indicates P < 0.05 compared with Comparative Example 2.

[0175] 4.4 Effects on xanthine oxidase activity in rat serum and liver

[0176] Compared with the blank control group, the serum XOD activity of rats in the model control group was significantly increased (P < 0.05); compared with the model control group, the serum XOD and liver XOD activities in the allopurinol tablet group were significantly decreased (P < 0.01), while the other treatment groups had no significant effect. The results showed that the granules in comparative example 1 had no significant effect on the serum XOD and liver XOD activities of rats with hyperuricemia model. The results are shown in Table 18.

[0177] Table 18 Effects of each group on rat serum and liver xanthine oxidase ( n=10)

[0178]

[0179] Note: Compared with the blank control group, "*" indicates P < 0.05, compared with the model control group, ΔΔ ” indicates P < 0.01.

[0180] 4.5 Macroscopic Observation of Kidneys and Histopathological Examination of Kidneys and Liver

[0181] like Figure 1It can be seen that the kidneys of the model control group were significantly swollen, increased in size, with white capsules, and white dot-like urate deposits on the surface, while the surfaces of the drug-treated groups only showed scattered urate deposits, which were red and white. Pathological sections showed that the cortex and medulla of the kidneys of the experimental animals in the blank control group had clear structures, the morphology and structure of the renal units were normal, there was no inflammatory cell infiltration in the interstitium, the liver hepatocyte cords were arranged in an orderly manner, the hepatocytes did not show degeneration or necrosis, and there was no congestion in the liver sinusoids; the kidneys of the experimental animals in the model control group had multifocal basophilia increased and flattened, the tubular lumen was dilated, scattered tubular epithelial cell necrosis was present, and some were accompanied by granuloma-like lesions, fibrous connective tissue proliferation in the interstitium, inflammatory cell infiltration was seen in the lumen and interstitium of some renal tubules, and the liver No obvious lesions were found in the kidneys; compared with the model control group, the degree of renal lesions in the experimental animals of each drug group was alleviated to a certain extent, the number of dilated renal tubules was reduced, the number of necrotic renal tubular epithelial cells and granulomatous lesions was reduced, and inflammatory cell infiltration was occasionally seen in the renal tubular lumen or interstitium of some experimental animals. The mean renal tissue pathology scores of the blank control group, model control group, comparative example 1, comparative example 2, embodiment 1, and allopurinol group were 0.0, 7.9, 6.5, 6.4, 6.0, and 6.1, respectively. The results of pathological scoring showed that: compared with the blank control group, the renal pathological score of the model control group was significantly increased (P < 0.01); compared with the model control group, the renal pathological scores of Comparative Example 1, Comparative Example 2, Example 1 and the allopurinol tablets group were significantly or significantly reduced (P < 0.05 or P < 0.01); compared with Comparative Example 1, the scores of Comparative Example 2 and Example 1 showed a downward trend, but no statistical difference was found; compared with Comparative Example 2, the score of Example 1 showed a downward trend, but no statistical difference was found; compared with Allopurinol tablets group 1, the score of Example 1 showed a downward trend, but no statistical difference was found. No obvious lesions were found in the liver of each medication group. The pathological results showed that Example 1 had a significant improvement effect on the renal pathological changes in hyperuricemia model rats. The results are shown in Tables 19 and Figure 2 、 3 .

[0182] Table 19 Effects of each group on the kidney pathological scores of hyperuricemia model rats ( n=10)

[0183]

[0184] Note: Compared with the blank control group, "**" indicates P < 0.01, compared with the model control group, " Δ " indicates P < 0.05," ΔΔ ” indicates P < 0.01.

[0185] 5. Conclusion

[0186] The test results showed that under the experimental conditions, the granules of Example 1 could significantly reduce the levels of CREA and UREA in rats, reduce the urine uric acid level and the kidney organ coefficient, and have a significant repair effect on kidney pathological changes. In addition, Example 1 was more effective than Comparative Examples 1 and 2. In summary, Example 1 has a significant therapeutic effect on rats with hyperuricemia model.

[0187] Experiment 2 Effect of the formula of Example 1 on gout model rats

[0188] 1. Purpose of the study

[0189] This experiment replicates the gout model rats, and provides experimental basis for the therapeutic effect of the formula granules of Example 1 on gout and the clinical application of the formula granules of Example 1.

[0190] 2.1 Test materials

[0191] Test substance (test sample): Chinese medicine composition of Example 1 and Comparative Example 1 and Comparative Example 2 (Guyitang (Hunan) Health Technology Co., Ltd.), 1g dry paste contains 8.545g crude drug, ointment, clinical dosage: 106g crude drug / day; clinical route: oral, clinical course of treatment: 1 month

[0192] Positive control drug: Name: Tongfengding Capsules, Specification: 0.4g×60 capsules, Manufacturer: Sichuan Shenghe Pharmaceutical Co., Ltd., Usage and Dosage: Oral. 4 capsules at a time, 3 times a day

[0193] Experimental animals: 60 SPF-grade SD male rats, weight range: 189.1-224.1 g (Hunan Slake Jingda Experimental Animal Co., Ltd.)

[0194] 3. Test methods

[0195] 3.1 Model construction and drug administration

[0196] 60 qualified SD rats of selection quarantine were randomly divided into 6 groups by body weight, namely blank control group, model control group, comparative example 1 group, comparative example 2 group, embodiment 1 group, Tongfengding capsule group, 10 in every group. After grouping, each group of rats was gavaged with the medicine of corresponding dose of 10mL / kg respectively, and blank control group and model control group were gavaged with equal volume of pure water, 1 time / day, for 9 consecutive days. Except blank control group on the 7th day, all the other groups of rats all prepared acute gouty arthritis model: rat was anesthetized with isoflurane, fixed in supine position, and injection needle was inserted into the right hind limb ankle joint cavity with 45 ° of angles with tibia, and 0.1mL 25mg / mL sodium urate solution was injected to induce acute gouty arthritis. Blank control group was injected with equal amount of normal saline with the above steps, and continued to administer 2d after modeling and finished.

[0197] 3.2 Dosage setting and grouping

[0198] The clinical intended dosage of the Chinese medicine composition of Example 1 and Comparative Examples 1 and 2 is 106 g crude drug / day, which is converted into a rat equivalent dose based on body surface area: 106 g crude drug / day × 0.018 ÷ 0.2 kg = 9.54 g crude drug / kg; the clinical intended dosage of the Tongfengding capsule composition for humans is 4.8 g / day, which is converted into a rat equivalent dose of 0.43 g / kg, and 2 times the equivalent dose is used as the administration dosage. A blank control group and a model control group were also set up, as shown in Table 20.

[0199] Table 20 Dosage design for each group

[0200]

[0201] Note: 1g dry paste powder is equivalent to 8.545g crude drug.

[0202] 3.3 Drug preparation:

[0203] The Chinese medicine composition of Example 1 and Comparative Examples 1 and 2: Weigh 4.48 g of the dry paste powder of the Chinese medicine composition of Example 1 and Comparative Examples 1 and 2, and add purified water to prepare 60.5 mL (0.074 g dry paste powder / mL);

[0204] Tongfengding Capsule Group: Take 9 Tongfengding Capsules (3.6g), add purified water and stir evenly to 124mL (0.029g / mL); 3.4 Test Indicators

[0205] 1. General Observation: After drug administration and model establishment, closely observe and record the appearance, behavior, secretions, excretions, and diet of each group of experimental animals. If an experimental animal is found dead or dying, perform an autopsy on it promptly. Weigh the experimental animals weekly.

[0206] 2. Measure the diameter of the rat's right hind limb 1 mm below the ankle joint at 0, 2, 4, 8, 12, 24, and 48 hours after sodium urate solution injection. Measure three times and take the average value to calculate the degree of joint swelling. Joint swelling (%) = (ankle joint diameter after MSU crystal injection at each time point / initial ankle joint diameter - 1) × 100%.

[0207] 3. Histopathological Examination: The synovial tissue was isolated from the right hind ankle joint of the rats and fixed in 10% neutral formalin. After decalcification, dehydration, embedding, and routine tissue sectioning, hematoxylin and eosin staining, histopathological examination was performed. Details of the histopathological evaluation criteria and scoring criteria are shown in Table 21.

[0208] Table 21 Synovial tissue pathology evaluation indicators and scoring standards

[0209]

[0210] 4.5 Result calculation and statistics

[0211] SPSS 16.0 software was used for data statistics, and the measurement data were expressed as mean ± standard deviation. For comparisons between multiple groups, normality and homogeneity of variance were first compared. When the variances were homogeneous and normal, one-way analysis of variance was used. When normality was not met, the non-parametric T test was used. When normality was met but the variances were not homogeneous, the Tamhane's T2 test was used. If normality was not met, the Kruskal-Wallis test was used, and pairwise comparisons were performed using the Mann-Whitney test. P < 0.05 indicated a statistically significant difference, and P < 0.01 indicated a statistically significant difference. Biological significance was considered in the evaluation.

[0212] 5. Experimental Results

[0213] 5.1 Effect on rat joint swelling

[0214] Result is as shown in Table 22: compared with blank control group, the joint swelling degree of model control group rats 2, 4, 8, 12, 24, 48 hours is all obvious or significantly increased (P < 0.05 or P < 0.01), prompting modeling success; Compared with model control group, comparative example 2, embodiment 1 rats obviously reduce (P < 0.05) at 48 hours joint swelling degree, and all other time points each group joint swelling degree has reduction trend, but has no statistical difference, embodiment 1 and comparative example 1 and comparative example 2 have reduction trend, but have no statistical difference, comparative example 2 and comparative example 1 have reduction trend, but have no statistical difference, embodiment 1 and tongfengding capsule group have reduction trend, but have no statistical difference. The above results show that comparative example 2 and embodiment 1 have the effect of reducing the joint swelling degree of acute gout model rats.

[0215] Table 22 Effects on rat joint swelling ( n=10)

[0216]

[0217] Note: Compared with the blank control group, * " indicates P < 0.05; " ** " indicates P < 0.01, compared with the model control group," Δ ” indicates P < 0.05.

[0218] 5.2 Pathological observation results of rat synovial tissue

[0219] In the blank control group, no pathological changes such as lining cell hyperplasia, hypertrophy, fibrous connective hyperplasia, etc. were observed in the lining layer of the synovial tissue of the ankle joint of the rats, and no pathological changes such as granulation tissue hyperplasia, vascular tissue ingrowth, and inflammatory cell infiltration were observed in the subsynovial tissue; in the model control group, lining cell hyperplasia, hypertrophy, fibrous connective tissue hyperplasia, granulation tissue hyperplasia, vascular tissue ingrowth, and inflammatory cell infiltration were observed in the synovial tissue of the ankle joint of the rats. Compared with the model control group, the lesion types of the experimental animals in each drug group were similar to those of the model control group, but the degree of lesions was slightly alleviated, namely, blank control group, Example 1, Tongfengding Capsule group, Comparative Example 2, Comparative Example 1, model control group, and the mean scores were 0, 4.5, 4.6, 5.3, 5.6, and 5.8, respectively. The results of pathological scoring showed that compared with the blank control group, the score of the model control group was significantly reduced (P<0.01); compared with the model control group, the scores of Example 1 and Tongfengding Capsule group were significantly reduced (P<0.05), and there was no significant difference in the scores of the comparative example 1 group and the comparative example 2 group, but there was a downward trend; compared with comparative example 1, there was no significant difference in the score of comparative example 2, but there was a downward trend, and the score of Example 1 was significantly reduced (P<0.05); compared with comparative example 2, there was no significant difference in the score of Example 1, but there was a downward trend; compared with the Tongfengding Capsule group, there was no significant difference in the score of Example 1, but there was a downward trend. The results are shown in Table 23. Pathological pictures are shown. Figure 4 .

[0220] Table 23 Effects on pathological scores of synovial tissue in rats with acute gout model ( n=10)

[0221]

[0222]

[0223] Note: Compared with the blank control group, "**" indicates P < 0.01; compared with the model control group, " Δ ” indicates P < 0.05; compared with Comparative Example 1, “▲” indicates P < 0.05.

[0224] The test results showed that under the test conditions, the Example 1 group had the effect of reducing the joint swelling of the acute gout model rats, and compared with the Comparative Example 1, Comparative Example 2 and Tongfengding Capsule group, the effect was better.

[0225] Example 5 Clinical analysis data of the Chinese medicine composition of Example 1

[0226] 102 patients who met the criteria for gout diagnosis were selected for observation and randomly divided into Example 1 and a control group. Among them, there were 30 male patients and 21 female patients in Example 1, aged 31 to 63 years old, with an average age of (46.27 ± 4.29) years, a course of disease of 3 months to 10 years, and an average of (3.15 ± 1.06) years. In the control group, there were 29 male patients and 22 female patients, aged 30 to 64 years old, with an average age of (46.85 ± 4.51) years, a course of disease of 4 months to 10 years, and an average of (3.37 ± 1.14) years. There was no statistical difference in gender, age, and course of disease between the two groups (P>0.05).

[0227] 4. Inclusion criteria

[0228] 4.1 Diagnostic criteria Western medicine diagnostic criteria Western medicine diagnostic criteria refer to the diagnostic criteria for acute gouty arthritis published by the American Rheumatology Association in 1997, which are as follows: (1) Specific urate crystals are present in joint fluid; (2) Urate crystals are detected in tophi using polarized light microscopy or chemical methods; (3) Contains 6 or more of the following 12 items (clinical, X-ray manifestations and laboratory tests). ① More than one acute arthritis attack; ② The peak of inflammation is reached within 1 day; ③ Monoarthritis attack; ④ Redness can be seen in the joint lesion; ⑤ Swelling or pain is manifested in the first metatarsophalangeal joint; ⑥ Unilateral involvement of the first metatarsophalangeal joint; ⑦ Unilateral involvement of the tarsal joint; ⑧ Suspected tophi; ⑨ Hyperuricemia; ⑩ X-ray shows asymmetric intra-articular swelling; X-rays showed subcortical cysts but no bone erosion; Negative joint fluid culture during the onset of joint inflammation; diagnosis can be made if any of the above (1), (2), and (3) are met.

[0229] 4.2 Exclusion criteria Patients with severe complications such as sepsis, intracranial infection, blood system diseases and severe heart, liver and kidney failure; patients who do not meet the inclusion criteria and have diseases with joint inflammation; patients with complications affecting the joints, patients who do not take the medication as prescribed, or patients who are allergic to the trial drugs or cannot tolerate the trial drugs; patients whose efficacy cannot be judged, or whose data are incomplete and affect the judgment of efficacy or safety; patients who do not take high-purine diets or other uric acid-lowering or analgesic drugs as prescribed by the doctor; patients who cannot complete the treatment for any reason.

[0230] 5. Treatment methods

[0231] The control group was given oral diclofenac sodium sustained-release tablets (0.1 g x 12 tablets, Sichuan Huaxin Pharmaceutical Co., Ltd.), one tablet at a time, once a day; the traditional Chinese medicine group was given the traditional Chinese medicine composition of Example 1, one bag at a time, 6.5 g per bag (equivalent to 35.3 g of decoction pieces), three times a day; both groups of patients were treated continuously for 1 month.

[0232] 6. Observation of therapeutic effects

[0233] The efficacy was judged in accordance with the "Guiding Principles for Clinical Research of New Traditional Chinese Medicines". Clinical cure: complete disappearance of symptoms, normal return of joint function, and normalization of major physical and chemical examination indicators; marked effect: disappearance of major symptoms, normal return of joint function, and basic normalization of major physical and chemical examination indicators; effective: basic disappearance of major symptoms, and improvement in major joint function and physical and chemical indicators; ineffective: no improvement in all aspects compared with before treatment; effective rate = (cured + markedly effective + effective) ÷ total number of cases × 100%.

[0234] 7. Statistical methods

[0235] Statistical methods: SPSS 16.0 statistical software was used for data analysis and comparison. The t-test was used for comparison of quantitative data, and the chi-square test was used for comparison of enumeration data. P < 0.05 indicated statistical significance.

[0236] Table 24 Comparison of disease efficacy between the two groups of patients [cases (%), numbers outside brackets are numbers, percentages inside brackets]

[0237]

[0238] Table 25 Comparison of adverse reactions in the two groups of patients [cases (%)]

[0239]

[0240] Note: Compared with the control group, "*" indicates P < 0.05

[0241] The research results showed that both the control group and the Example 1 group had good therapeutic effects on gout. The therapeutic effect of the Example 1 group was better than that of the control group, but there was no statistical difference (P>0.05). Compared with the occurrence of adverse reactions, the Example 1 group had no adverse reactions, which was significantly different from the control group, with statistical differences (P<0.05), and high safety.

[0242] Example 6

[0243] A traditional Chinese medicine composition for treating acute gout is composed of the following components by weight: 8 parts of Rhizoma Smilacis Glabrae, 6 parts of Polygonum Cuspidati, 6 parts of Plantago Seed, 6 parts of Rhizoma Atractylodis Macrocephalae with bran, 6 parts of Phellodendron Amurense, 2 parts of Cyathulae, 2 parts of Coix Seed, 2 parts of Herba Dichroae, 2 parts of Fructus Liquidambar formosanae, 2 parts of Cortex Fraxini, 2 parts of Hedyotis Diffusa, 6 parts of Rheum Officinale, 2 parts of Caulis Schizonepetae, 2 parts of Caulis Trachelospermi, 2 parts of Caulis Lonicerae, 2 parts of Carthamus Tinctorius, 2 parts of Rhizoma Prunellae, 2 parts of Lithospermum Officinale, 2 parts of Salvia miltiorrhiza, 2 parts of Stephania tetrandra, and 9 parts of roasted Astragalus. The preparation method is the same as that of Example 1.

[0244] The product of Example 6 has also been verified to have no toxic side effects and its therapeutic effect is similar to that of Example 1, so it will not be repeated here.

[0245] The above is a specific embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any technician familiar with the technical field, within the technical scope disclosed by the present invention, who makes equivalent replacements or changes based on the technical solutions and concepts of the present invention, should be covered by the scope of protection of the claims of the present invention.

Claims

1. A Chinese medicine composition for treating gout, characterized in that: By weight, it is made from the following components: 8-12 parts of Smilax glabra, 5-9 parts of Polygonum cuspidatum, 5-9 parts of Plantago seed with salt, 5-9 parts of stir-fried Atractylodes lancea with bran, 5-9 parts of Phellodendron amurense, 1-4 parts of Cyathula root, 1-4 parts of Coix seed, 1-4 parts of Herba Cyperi, 1-4 parts of Rhizoma Clerodendrum Smilacis Glabrae, 1-4 parts of Cortex Fragrantis, 1-4 parts of Hedyotis diffusa, 1-4 parts of Rhubarb, 1-4 parts of Caulis Scutellariae, 1-4 parts of Caulis Trachelospermi, 1-4 parts of Caulis Loniceraes, 1-4 parts of Carthamus tinctorius, 1-4 parts of Stewed Peach Kernel, 1-4 parts of Lithospermum erythrorhizon, 1-4 parts of Salvia miltiorrhiza, 1-4 parts of Stephania tetrandra, and 12-18 parts of roasted Astragalus.

2. A Chinese medicine composition for treating gout, characterized in that: By weight, it is made from the following components: 10 parts of Rhizoma Smilacis Glabrae, 7 parts of Polygonum Cuspidati, 7 parts of Plantago seed with salt, 7 parts of stir-fried Atractylodes lancea with bran, 7 parts of Phellodendron amurense, 3 parts of Cyathula root, 3 parts of Coix seeds, 3 parts of Herba Dichroae, 3 parts of Fructus Liquidambardi, 3 parts of Cortex Fraxini, 3 parts of Hedyotis diffusa, 7 parts of Rheum officinale, 3 parts of Caulis Scutellariae, 3 parts of Caulis Sargentodoxae, 3 parts of Caulis Trachelospermi, 3 parts of Caulis Lonicerae, 3 parts of Carthamus tinctorius, 3 parts of boiled peach kernel, 3 parts of Lithospermum officinale, 3 parts of Salvia miltiorrhiza, 3 parts of Stephania tetrandra, and 10 parts of roasted Astragalus.

3. A Chinese medicine composition for treating gout, characterized in that: By weight, it is made from the following components: 8 parts of Rhizoma Smilacis Glabrae, 6 parts of Polygonum Cuspidati, 6 parts of Plantago seed with salt, 6 parts of stir-fried Atractylodes lancea with bran, 6 parts of Phellodendron amurense, 2 parts of Cyathula root, 2 parts of Coix seeds, 2 parts of Herba Dichroae, 2 parts of Fructus Liquidambardi, 2 parts of Cortex Fraxini, 2 parts of Hedyotis diffusa, 6 parts of Rheum officinale, 2 parts of Caulis Schizonepetae, 2 parts of Caulis Trachelospermi, 2 parts of Caulis Lonicerae, 2 parts of Carthamus tinctorius, 2 parts of Semen Persicae, 2 parts of Radix Lithospermi, 2 parts of Salvia miltiorrhiza, 2 parts of Stephania tetrandra, and 9 parts of roasted Astragalus.

4. A method for preparing the Chinese medicine composition for treating gout according to any one of claims 1 to 3, characterized in that: The following steps are involved: The above 22 Chinese medicinal materials are decocted with water for 2-3 times, with 10-12 times of water added each time, and decocted for 1-2 hours; the filtrates are combined, and the filtrates are concentrated under reduced pressure to a clear paste with a relative density of 1.05-1.10 at 60°C, centrifuged, and the centrifuge liquid is further concentrated under reduced pressure to a clear paste with a relative density of 1.20-1.30, and then vacuum dried to obtain the Chinese medicinal composition.

5. The method for preparing the Chinese medicine composition for treating gout according to claim 4, wherein: The traditional Chinese medicine composition is prepared into any one of tablets, granules, capsules, pills, mixtures, decoctions or powders.

6. Use of the Chinese medicine composition according to any one of claims 1 to 3 or the Chinese medicine composition prepared by the method of claim 4 or 5 in preparing a drug for treating gout.

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