CN112870305A - Pharmaceutical composition and preparation for treating gout, and preparation method and application thereof - Google Patents

Abstract

The invention discloses a pharmaceutical composition for treating gout, a preparation method and an application thereof, wherein the pharmaceutical composition comprises the following components in parts by weight: 15 parts of rhizoma polygonati, 12 parts of Chinese holly leaf, 15 parts of lily, 15 parts of coix seed, 15 parts of corn stigma, 8 parts of mustard seed, 10 parts of kudzu root and 10 parts of lophatherum gracile, and the Chinese medicinal composition is prepared by the steps of pretreatment, alcohol extraction, water extraction and post-treatment. The pharmaceutical composition and the preparation formula of the invention are scientific and reasonable, and the medicine for treating gout prepared by the invention has the effects of invigorating spleen and kidney, clearing heat and promoting diuresis, and the like, and can obviously improve the symptoms of hyperuricemia accompanied by soreness of waist and knees, arthralgia such as stubborn, local joint deformation, light day and heavy night, gait difficulty and the like, and has better treatment effect. All the Chinese medicinal materials are taken from the 'food and drug homology' variety, and are safe and reliable. The medicine for treating gout, which is prepared from the medicine composition and the preparation, has the advantages of unique curative effect, small side effect and no toxic or side effect, and can prevent, relieve and treat gout.

Description

Pharmaceutical composition and preparation for treating gout, and preparation method and application thereof

Technical Field

The invention belongs to the technical field of medicines, and particularly relates to a pharmaceutical composition and a preparation for treating gout, and a preparation method and application thereof.

Background

Gout is a kind of crystalline arthritis caused by long-term deposition of mono-natriuretic urate in vivo, is directly related to hyperuricemia caused by hypouricemia and/or purine metabolic disorder, and belongs to the scope of metabolic rheumatism. Hyperuricemia is an essential biochemical basis for the development of gout. Gout is mainly characterized by red, swollen and painful joints, light day and heavy night and limited activity. The Chinese of "Jingyue quan Shu" is that: the syndrome of wind arthralgia refers to gout, which is also known as gout in our country. "sui" the syndrome of various sources of disease records: the pattern of wind over the joints is marked by shortness of breath, spontaneous sweating, and pain over the joints is intolerable … …. Also, it is caused by wind pathogen due to blood and qi deficiency. "Song, xu Hui" is recorded in "general affairs' prescription: "Zhi Bai Hu Tu Jie … … -shaped fly-bite, daytime-night drama".

Summarizing the clinical experience of doctors in different generations, most doctors believe that gout is caused by phlegm stagnation and meridian obstruction due to innate deficiency, thick taste of acquired ointment, stasis and obstruction of exogenous pathogenic factors, dysfunction of spleen in transport and unsmooth circulation of qi and blood. The main pathological factors of gout are: wind, dampness, cold, heat, phlegm and blood stasis. The Yuan Dynasty Zhu Danxi emphasizes internal causes of disease, and is recorded in the theory of Greek remainder theory and gout theory: the patients with gout feel pain because they boil themselves due to blood heat and then they feel pain in cold water, in wet land, in cool wind by fan, or in lying wind … …. "shou shi baoyuan" indicates: gout patients suffer from the symptoms of qi deficiency, dysfunction of conditioning, wind-cold, summer-heat and dampness. "Gong Yangxian in the book of Wan Bing Hui Chun" (Wan Bing Chun of disease): gout is also … … pain caused by blood-qi and rheumatism … …. Or the exertion, the struggle between cold and water; or people who are drunken and lie … … with gout are mostly wind; in the following, it is mostly damp. The basic pathogenesis of gout is the disease caused by spleen dysfunction and dampness-heat accumulation in joints due to the addiction of fat and sweet. And the pathological characteristics of 'originating in middle energizer, flowing and stagnating in lower energizer, and being diseased in lower limbs' and 'originating in spleen and stomach and finally in liver and kidney' are provided.

The traditional Chinese medicine considers that the disease is caused by spleen and kidney deficiency, qi transformation failure (qi transformation disorder), retention of damp turbidity in the interior, qi obstruction and turbid pathogen diffusion in the triple energizer; dampness retention can block qi movement, which can lead to dysfunction of the spleen in transportation and retention of food and body fluids as pathogens; dampness obstructing collaterals, kidney qi failing to control, kidney steaming failing to control, clear and turbid pathogens failing to control, and discharge failing to control, the dampness and turbid will be more abundant, the internal organs will be dry, the limbs will be blocked, the spleen and kidney will be damaged, and the deficiency of spleen and kidney will occur. Based on the ancient and modern literature, the professor of Renshen Renwei is based on long-term clinical practice that kidney tonifying and spleen invigorating can store essence in kidney, the generation and generation of kidney qi are active, the kidney qi is sufficient, qi activities of various viscera rise and fall smoothly, the kidney is opened and closed to ensure that the essence stored in kidney is retained and turbid pathogenic factors metabolized by kidney can be discharged along with urine; spleen invigorating can lead to the abundance of spleen qi, spleen qi can lead to the transformation of spleen, so that essence of water and food can circulate in the channels and are distributed in four regions, so that damp-turbidity is difficult to grow, the channels and collaterals are smooth, the meridian qi is unobstructed, and damp-turbidity is transformed without being retained. Therefore, gout caused by weakness of spleen and stomach and spleen deficiency and dampness accumulation is mainly treated by the principles of tonifying spleen and kidney, clearing heat and promoting diuresis, regulating vital energy and regulating blood.

Disclosure of Invention

The first purpose of the invention is to provide a pharmaceutical composition for treating gout; the second purpose is to provide a preparation method of the pharmaceutical composition for treating gout; the third purpose is to provide the preparation of the pharmaceutical composition for treating gout; the fourth purpose is to provide the application of the pharmaceutical composition for treating gout.

The first purpose of the invention is realized by that the pharmaceutical composition comprises, by weight, 0.1-99 parts of rhizoma polygonati, 0.1-99 parts of Chinese holly leaf, 0.1-99 parts of lily, 0.1-99 parts of coix seed, 0.1-99 parts of corn stigma, 0.1-99 parts of yellow mustard seed, 0.1-99 parts of kudzu root and 0.1-99 parts of lophatherum gracile, and is prepared by the steps of pretreatment, extraction and post-treatment.

The second purpose of the invention is realized by the steps of pretreatment, extraction and refining post-treatment, which specifically comprises the following steps:

A. pretreatment: weighing the raw materials according to the composition ratio, and crushing the raw materials and sieving the crushed raw materials by a sieve of 20-100 meshes for later use;

B. alcohol extraction: mixing the processed raw material medicines of Chinese holly leaf, kudzu root and yellow mustard seed, soaking the mixture for 2 to 4 hours by using 60 to 90 percent ethanol, adding 70 percent ethanol which is 15 to 18 times of the total weight of the raw materials for the first time, extracting the mixture for 80 minutes by using an ultrasonic method, adding 8 to 10 times of 70 percent ethanol for the second time, performing ultrasonic treatment for 40 minutes, combining filtrates, filtering, concentrating under reduced pressure until the relative density is between 1.05 and 1.18, adding 0.02 to 0.08 percent chitosan for clarification, standing for more than 24 hours, filtering to obtain a supernatant, concentrating under reduced pressure until the relative density is more than 1.30, and drying the supernatant to obtain a dry extract;

C. water extraction: mixing the pretreated rhizoma polygonati, lily, coix seed, corn stigma and lophatherum gracile, soaking the mixture for 24 hours by using 15 times of water, supplementing the water absorption amount, decocting for 2 hours for the first time, adding 10 times of water for each decocting for 1 hour for the second time and the third time, combining the decoctions for three times, filtering, concentrating under reduced pressure until the relative density is 1.15-1.20, adding 0.03-0.06% of ZTC for clarification, standing for more than 12 hours, centrifuging, taking supernatant, concentrating under reduced pressure until the relative density is more than 1.30, and drying to obtain dry extract;

D. and (3) post-treatment: mixing the two dry extracts, pulverizing, sieving with 80-100 mesh fine powder, adding sieved maltose and lactose, mixing, making tea, drying, and packaging to obtain the final product.

The pharmaceutical composition is added with pharmaceutically acceptable auxiliary materials to prepare granules, tablets, syrups, capsules, soft capsules and dropping pills

The pharmaceutical composition disclosed by the invention is applied to preparation of medicines for preventing and treating gout caused by high uric acid.

The invention provides a medicinal composition formula for treating gout, which has unique curative effect and small side effect, and a preparation process and application thereof, and has better curative effect and no toxic or side effect on the diseases.

Rhizoma polygonati: polygonatum sibiricum Delar. ex Redoute [ P.chinensis Kunth ] is the rhizome of Polygonatum sibiricum, Polygonatum cyrtonema and Polygonatum kingianum of Liliaceae. Rhizoma polygonati is also named: tuotu kombuci et al (Ben Cao of Ouian wildernia), JITOQI, WUYA QI, and HUANGJICAI (Chinese materia Medica). Sweet in flavor and neutral in nature. It enters spleen, lung and kidney meridians. Article Hui Jing Yao (essence of article): "sweet taste, mild nature". Thin qi, yin in yang, and smelly. "(materia Medica): sweet and slightly pungent in flavor and warm in nature. "the materia Medica: it is specialized in spleen, lung and kidney. "(renewal of materia Medica): enter heart, spleen, lung and kidney meridians. "Tianbao Bencao": bitter and sweet taste, slightly warm. [ function and indication ] nourishing yin and moistening lung, invigorating spleen and replenishing qi, nourishing kidney and replenishing essence. Mainly treats cough caused by yin deficiency and lung dryness; spleen deficiency, asthenia, poor appetite, dry mouth, diabetes; kidney deficiency, soreness and weakness of waist and knees, impotence, spermatorrhea, tinnitus, dim eyesight, premature graying of hair, asthenia, emaciation and wind scab. The bibliography: to strengthen the middle-jiao and replenish qi, dispel wind-damp and calm the five internal organs. Can be taken for a long time to reduce weight and prolong life without hunger. "Rihuazi": tonifying five strains and seven injuries, helping bones and muscles, allaying hunger, resisting cold and summer heat, tonifying spleen and stomach, and moistening heart and lung. Jiu steam Jiu storm is taken singly, and the skin is kept after eating Jiu storm. "compendium" (compendium): to tonify deficiency, stop cold and heat, and fill essence and marrow. "the materia Medica: to tonify spleen yin. "modern practical Chinese medicine": "is a tonic medicine, and is effective in treating asthenia after illness. It is also an antipyretic for intermittent fever, gout, periostitis, etc. "Sichuan Chinese materia medica Zhi (1960 edition): to tonify kidney and nourish yin. It is indicated for spleen deficiency and yellowish complexion, cough due to lung deficiency, soreness and weakness of tendons and bones, and qi and blood deficiency after delivery. Huang Jing is indicated for spleen deficiency manifested as yellow, lassitude, poor appetite, or fluid deficiency manifested as dry mouth, poor appetite, red tongue with little coating. Huang Jing can nourish spleen and stomach qi and nourish spleen and stomach yin. Rhizoma Polygonati can be used for quenching thirst, and has effects in invigorating qi, nourishing yin, invigorating spleen, moistening lung, and invigorating kidney. Can be used for treating weakness of spleen and stomach, asthenia, xerostomia, dry cough due to lung deficiency, insufficiency of essence and blood, and diabetes due to internal heat. Modern researches show that rhizome of polygonatum contains mucus, starch and sugar, and rhizome of polygonatum cyrtonema contains Azetidine-2-carboxylic acid (Azetidine-2-carboxylic acid), aspartic acid (aspartic acid), Homoserine (Homoserine), diaminobutyric acid (diaminobutyric acid), digitoside (digitaciloside) and various anthraquinone compounds. Rhizoma Polygonati has effects of resisting anoxia, relieving fatigue, and resisting aging; can enhance immunity and metabolism; has effects in lowering blood sugar and tonifying heart. According to the record of modern Chinese herbal medicine, folk sealwort has the function of treating gout.

Chinese holly leaf: ilex cornuta Lindl. ex Paxt. is dry leaf of Ilex cornuta Lindl. of Aquifoliaceae. Alias: chinese holly leaf "Ben Cao Shi Yi", Fei Er Ci "gang mu", Gou Gu Ci Ji Shen Cai Hui Yan, eight-square tea "Ben Cao Shi Xin", mouse Ci, Shi Mahonia leaf "gang mu Shi Yi", Tiger Ci Jie in Jiangsu province, and Yangjian Ci in Hunan province, etc. The Chinese holly leaf has the following properties: bitter; and (6) cooling. Meridian tropism: the liver meridian; the kidney channel. Compendium (compendium): slightly bitter, cool and nontoxic. "(Ben Cao Jing Shu): herbs that have both negative smell and enter liver and kidney. "(the materia Medica is New): "bitter and neutral smell. "the materia Medica is required: sweet, bland, slightly bitter and cold. "[ function and indication ] function: clearing deficiency heat; benefiting liver and kidney; dispel wind-damp. The main treatment is as follows: yin deficiency with internal heat; cough with hemoptysis; light headedness; soreness and weakness of waist and knees; rheumatic arthralgia; vitiligo. The original menstrual period was: for internal injury, blood loss and fistula, it can nourish blood and qi. "(the materia Medica is New): "produce saliva to quench thirst, dispel wind". "the nature of the drug is surely used": to enter liver and kidney to benefit yin and expel wind. "the materia medica departs from the new" to produce saliva and slake thirst, so the leaf is very wonderful to replace tea and dispel wind. 'Ben Cao Jing Shu' is that the Chinese holly leaves no odor, but the cloud of the appearance container is bitter, cold and nontoxic. Herbs that have both negative smell and enter liver and kidney. But it enters liver, so it is mainly indicated for leucoderma, while liver covering is the location of Fengmu, it stores blood, blood deficiency gives rise to heat, even heat gives rise to wind, bitter and cold can cool blood and clear heat. It can tonify waist and knees, the waist is house of kidney, and kidney deficiency can cause dampness-heat, while waist and knees are unfavorable; the kidney is the strong organ, while deficiency causes heat and softness, so it is hard to libido, and bitter in taste and hard in nature. The herb is bitter in flavor and enters kidney to strengthen the sexual ear; when kidney qi is excessive, it can remove damp-heat, while the waist and knees are healthy . The secret recipe takes the juice of the secret recipe and is used for treating the phlegm-fire. The phlegm fire does not burn the lung and boil the phlegm liquid caused by yin deficiency fire. The medicine directly enters the foot-shaoyin channel, and nourishes yin qi, so that phlegm fire is self-eliminated, which is also the intention of drawing firewood from the bottom of the kettle. It can also dispel wind-toxin and malignant sores. The red bayberry with the symptom of toxin-deposition has been taken for thirty years, and the sore is healed and the color is changed little, so the heat-clearing and blood-cooling effects of the red bayberry are taken. The Chinese holly leaf has the following effects: the theory of traditional Chinese medicine holds that Chinese holly leaf has the efficacies of clearing heat and nourishing yin, calming liver and tonifying kidney, dispelling wind and dredging collaterals and the like [3], and is used for treating diseases such as tuberculosis hemoptysis, bone steaming and tidal fever, dizziness, hypertension and the like.

Modern phytochemistry research shows that triterpenes and glycosides thereof are main components in Chinese holly leaves, and in addition, a large amount of flavonoids are contained. Folium Ilicis Cornutae has effects in resisting fertility, dilating coronary artery, resisting bacteria, and inhibiting excessive activation and proliferation of immunocyte. The Chinese holly leaf also has the functions of reducing blood fat and blood sugar and resisting inflammation, and has certain curative effect on gout patients.

Lily: lilium brownise f.e.brown var. viridulum Baker [ l.brownnii f.e.brown Miellez var. colchester (Van Houtt.). wils.ex Elwes ] is a dried fleshy bulb of liliaceae plants, lily, Lilium crispum, massicot, Lilium scholarii, etc. Also named: nostoc nocturna's herbal former, Baihua Baihe's empirical Collection, Lily bulb's compendium of Xinhua materia Medica, Lilium tenuifolium, Lotus flower, Cleistocalyx operculatus, and Lotus flower's dictionary of Chinese medicine. [ property of medicine ] is sweet, slightly bitter and slightly cold in taste. It enters heart and lung meridians. The book Jing: "sweet and mild". "Addite records": is nontoxic. "treatise on drug Property: "has little toxicity. "Rihuazi": "Red lily: cool and non-toxic. "the materia Medica of saving wasteland: "gan xin, ping. "(Pin Hui Jing Yao": "sweet taste, mild nature". The thin qi indicates yin in yang. Smelling the fish. "(Ben Cao Jing Shu): sweet and slightly cold in flavor. "(the summary of the present materia Medica): "enter the taiyang meridians of hand and foot, hand and foot jueyin, hand and foot yangming meridians. [ function and indications ] nourish yin and moisten lung, clear heart and induce tranquilization. It can be used for treating chronic cough due to yin deficiency, blood-stained sputum, late stage of febrile disease, and asthenia, vexation, pavor, insomnia, dreaminess, absentmindedness, carbuncle, swelling, and eczema due to emotional disorder. The book Jing: "dominating pathogenic qi, abdominal distension and heart pain". Relieve constipation, strengthen the middle-jiao and replenish qi. "Addite records": "remove edema, distention and fullness, cold and heat, relieve pain, difficult lactation, throat impediment, stop nasal discharge and lacrimation". "treatise on drug Property: main evil and ghost charm, nasal discharge and even discharge, remove urgency, fullness and pain in the lower heart, treat beriberi and hot cough. "Rihuazi": to calm heart, secure gallbladder, nourish mind and nourish five zang organs. For epilepsy, crying, mania, palpitation, poison qi, mammary abscess, back and sores and swelling, it is indicated for hematogenous and mania in postpartum. "(the summary of the present materia Medica): nourish lung qi, moisten dryness of spleen. It is indicated for cough due to lung heat, bone-steaming, cold-heat, dryness of spleen fire, and dry and astringent large intestine. The more this method in Wai Tai Mi Yao means that lily is a disease which is accompanied by lingering mind and bitter name because there is no heat left after typhoid, so that lily can clear heat in lung and stomach, regulate water passage and induce stagnated heat. For instance, swelling and edema should be considered as heat-resisting qi stagnation, and all prescriptions are contraindicated for cold-dampness stagnation and spleen-kidney yang deficiency. The right of discrimination means that it is suitable for treating beriberi and treating urgent heart fullness with heat. The rule of choice is also mainly heat cough, so ancient times means cough relieving, and the syndrome of extreme lung heat with burning of qi and fire is legal; cough due to wind-cold affecting the exterior, especially prohibited, caused by lung qi failing to disperse. According to the ancient prescription, lily and coltsfoot flower are decocted together to form an ointment, namely Baihua ointment, which is used for treating the disease of long-term cough with phlegm and blood, and also for treating fire excess from yin deficiency and dryness-heat on the upper part, so that the traditional Chinese medicine is prepared by moistening lily to reduce fire, and combined with the mild temperature of coltsfoot to release heat, so that qi and fire are diffused, and lung deficiency is nourished and benefited, thereby being a treatment. While the generation is common or lily is used to treat cough due to exogenous pathogens, it is not free from the inhibition of cold descending and stopping, and prevents the lung from being obstructed in the air chamber, so that exogenous pathogens cannot be released .

Modern research shows that: the lily bulb contains various alkaloids such as colchicine, starch, protein, fat, etc. Modern pharmacological actions: 1. has remarkable effect of eliminating phlegm. 2. After the mice with sedation stop eating for 8 hours, respectively using iglily 20g/kg, using wild jujube seed as positive control, using physiological saline as blank, administering ip pentobarbital sodium 40mg/kg for 30 minutes, and using the time from disappearance of righting reflex to recovery as the index of sleep. The effect on the subthreshold dose sleep rate of sodium pentobarbital was also observed. All have the functions of obviously increasing the sleep time of the sodium pentobarbital and the sleep rate of the subthreshold dose, and indicate that the medicament has obvious sedative effect. 3. Nourishing yin and moistening lung. 4. Has tonic effect. 5. The colchicine contained in the product can inhibit synthesis of uric acid.

Coix seed: coix lacryma-jobi L.var. mayuen (Roman.) Stapf is dried mature seed of Coicis semen of Gramineae. The effective ingredients are recorded in the chapter records of the legend, the Thomas oryzae recorded in the chapter records of Qianjin food therapy, the pearl of Job's tears recorded in the picture of the materia Medica, the ancient materia Medica of Job's tears recorded in the picture of the Secondary plain, the ancient materia Medica of Job's tears recorded in the picture of the Chinese materia medica, the ancient materia Medica of the Ling Zi recorded in the picture of the clinical evidence, the Chinese medicinal form experience identification of six cereals recorded in the Chinese medicinal form, the ancient materia medica of Guizhou, the ancient materia Medica recorded in the Chinese medicinal materials of the corn, the water corn, the hooked rice recorded in the northeast China medicinal plant record, and the. Sweet and bland in flavor, slightly cold in nature. It enters spleen, stomach and lung meridians. The book Jing: sweet and slightly cold in flavor. "diet therapy materia Medica: "good sex. "(Pin Hui Jing Yao": the thin qi indicates the yin in yang. Smelling and fragrant. "compendium": yangming meridian herbs also. "Lei Gong processing the drug property: it enters five meridians of lung, spleen, liver, stomach and large intestine. "(Ben Cao Jing Shu): "sweet, light and slightly cold". Yang is middle-yin and descending is also descending. "New compilation of materia Medica: it enters spleen and kidney meridians and also enters lung. "[ function and indications ] efficacy: promoting diuresis, invigorating spleen, relieving rigidity of muscles, relieving arthralgia, clearing away heat and toxic materials, benefiting lung, expelling pus, nourishing spleen and stomach, and strengthening tendons and bones. The main treatment is as follows: edema, beriberi, dribbling urination, damp-heat disease, diarrhea, leukorrhagia, rheumatic arthralgia, muscular spasm, pulmonary abscess, intestinal abscess, and verruca plana. The book Jing: the spasm of the main tendons, failure to bend and stretch, and arthralgia due to wind-dampness go on. Long-term taking can lighten the body and tonify qi. "Addite records": it can remove the pathogenic factors of muscles and bones, promote the function of intestines and stomach, and eliminate edema. "treatise on drug Property: it can cure hot wind and spasm of muscles and vessels, and can be eaten by people. Lung fistula is mainly associated with lung qi, profuse blood vomiting, cough, nasal discharge and qi ascending. Swelling due to toxin of radix seu herba Schisandrae Sphenantherae. "(materia Medica Shi Yi): "no hunger, warm qi and light weight". "boiling juice and drinking mainly quench thirst". "compendium" (compendium): to invigorate the spleen and nourish the stomach, tonify the lung and clear heat, remove wind and remove dampness. For cold air, it is eaten after being drunk. Decocted for decoction, it can induce diuresis and heat stranguria. "(renewal of materia Medica): tonifying spleen earth, purging spleen fire, clearing lung heat, benefiting lung qi, dispelling wind and removing dampness, and relieving epigastric distention. The Benjing Shu Zheng (the sparse meridians): the theory is to tonify qi, remove dampness, harmonize the middle energizer and invigorate the spleen, while Job's tears are similar to the operation, but not the difference of millicentics and the spurious phenomenon of thousands of miles are known. When the physician is covered with the mask, the physician is warm and the Job's tears are slightly cold, and when the physician is cloudy and tasteless, the physician is sweet and pungent and the Job's tears are sweet and light. Moreover, the odor of the Job's tears is thick and the odor of the Job's tears is thin, which is not consistent with equal. It is recorded in the book of Jinkui Yao, spasm and dampness scorpion, which is marked as dampness disturbing pain in the home, and should be used with Ma Huang plus Shu Tang to generate sweat at home, it should be used with cautions to avoid fire attack. It is called as the pain of the patient, and the fever is severe in the late afternoon, and the disease is caused by sweating and wind or chronic injury and cold, and can be combined with Ma Huang xing ren Yi gan Cao Tang. Patients with restlessness and pain, dampness and cold; the pain of one body is accompanied by dampness and wind. Cold changes from yin to yang and wind changes from yang to yang. So it is a sun with restlessness and pain; the patient with fever in the afternoon belongs to yangming. It is suitable for treating sweating due to the sun, and for treating yang-deficiency syndrome, it is suitable for clearing heat due to sweating, and for relieving yang-deficiency syndrome due to heat-clearing, it is suitable for treating sweating due to the use of Zhu Gui, and it is suitable for treating heat-clearing due to the use of Yi ren. Coicis semen can be used for treating retention of damp-heat in the interior, and for scanty and brownish urine, it can be used with pulvis Talci and medulla Tetrapanacis; for damp-warm disease with pathogenic dampness in qi system and predominant dampness, it is combined with xing ren, Dou kou ren, Zhu Ye and mu Tong, etc. It is also indicated for edema due to spleen deficiency, swelling and pain of beriberi, and combined with Fu Ling, Bai Jing, mu Gua and Wu Zhu Yu, etc.

Modern research shows that: coix seed contains Coix seed ester (Coixololide); and a fatty oil containing myristic acid (myristic acid), campesterol (campesterol), palmitic acid, 8-octadecenoic acid, stigmasterol, etc., and further containing amino acids, proteins, and saccharides. Coix seed also has a certain effect of reducing blood uric acid.

Corn silk: zea mays L. is stigma and stigma of Zea mays L. Also named Yumaixu (Yunnan materia Medica), Wushu millet pistil (modern practical Chinese medicine), and bang Mao (Hebei medicinal materials). The original plant corn is named as corn sorghum ' compendium ', Mussah wheat, Imperial wheat ' stay green Rizhao ' rice silk, Xifan wheat ' study nursery miscellaneous Shu ', corn, Yumai, corn Shushu ' agriculture political complete book ', Jongqun ' fang spectral ', red silk wheat ' Monghua Huozhi's will, Job's tears ' book, corn, Lu Gu, corn ' Qimin four shu's, Xitian wheat ' Pingxiang county Bing Zhi ', Yushu's grove's book ', Piri's book of famous curiosity's, Setarian's diet book of living things, pearl rice ' Erya Gu's exam, millet and corn ' Ling nan's book of collecting drugs ' and's bud ' Chinese medicinal plant's material '. Sweet in flavor and neutral in nature. It enters stomach and large intestine meridians. The description of the Dian nan materia Medica: sweet, neutral and nontoxic. "(Med et Med. Property): "enter hand and foot yangming meridians. 'the function and the indication' regulate the middle energizer and stimulate the appetite, induce diuresis and reduce edema. It can be used for treating anorexia, dysuresia, edema, and lithangiuria. The description of the Dian nan materia Medica: regulating stomach and regulating middle warmer, eliminating dampness, dispelling pathogenic fire and clearing heat. "(Med et Med. Property): "Yifei Ning Xin". "(materia Medica tuichen): "is a stomachic. It also has the action of inducing diuresis when decocted. "

Modern research shows that: the corn stigma has the following effects: 1. the corn stigma decoction has the effect of reducing blood fat for patients with hyperlipidemia, thereby protecting heart and reducing incidence of ischemic cardiovascular diseases (including coronary heart disease and ischemic stroke). 2. The diuretic effect is that the corn stigma and corn stigma water decoction is 5g/kg and 10g/kg for intragastric administration, the bear obviously increases the urine volume of the conscious rabbit in 1 and 2 hours after administration, and the high-dose group has strong effect which is weaker than that of furosemide but has lasting effect. 3. Blood pressure lowering effect, and the corn stigma water extract, ethanol extract and decoction can be administered topically to anesthetized dogs, cats and rabbits. 4. The corn stigma has the functions of promoting bile secretion and promoting bile excretion, and can reduce organic matters and residues in bile, and reduce viscosity, specific gravity and bilirubin content. 5. The corn stigma fermented preparation has the function of reducing blood sugar, and the fermented preparation of the corn stigma has obvious blood sugar reducing effect on rabbits; the water decoction is 7, 5, 15 and 30g/kg, and is perfused for 7 days continuously, which has obvious treatment effect on mouse diabetes caused by alloxan and also has obvious blood sugar reducing effect on mouse hyperglycemia caused by glucose and epinephrine. 6. Other effects, the corn stigma water releasing agent is 15g/kg, 30g/kg, and the gavage is carried out for 7d, so that the serum cholesterol content of the hypercholesteremia mice can be obviously reduced. The effect of the corn stigma flavone extract on a rat gouty arthritis model caused by sodium urate. Research shows that the manic joints of the rats in the model control group have obvious swelling, the levels of inflammatory factors (IL-la, IL-6 and TNF-a, cell adhesion factor ICAM-1 and matrix metalloproteinase MMP-1) in blood plasma are obviously higher than those of the control group in the blank group, which shows that the preparation of the gouty arthritis model is successful, after the rats in the gouty arthritis model are infused with high and medium doses of corn silk flavone extract, the swelling degree of the manic joints of the rats is obviously reduced, simultaneously, the plasma IL-1a, IL-6, TNF-a, ICAM-1 and MMP-1 level is also obviously reduced, and can improve the pathological and histological change of the manic joint, which shows that the corn stigma flavone extract has better effect of resisting the gouty arthritis, the action mechanism of the drug is probably to play a role in relieving inflammation of a model rat by inhibiting the generation and the release of inflammatory mediator factors.

Yellow mustard seed: brassica juncea (L.) Czern. et Coss. is a dry, mature seed of Brassica juncea, and can be used as a medicine. And (3) synonymy: mustard seed, Sun Tianren Ji Xiao Fang, green vegetables, Classification of herbaceous Properties. Medicine property: pungent flavor, warm nature and slight toxicity. It enters stomach and lung meridians. Qianjin dietetic therapy: pungent and toxic. "baoqing materia Medica compromise": pungent, spicy, warm and nontoxic. "compendium" (compendium): "pungent and hot". "(De-Cang Ben Cao): "enter the hand and pass through the yin channel. [ function and indications ] warming the middle-jiao to dispel cold, eliminating phlegm to induce resuscitation, dredging collaterals and relieving swelling. Can be used for treating emesis due to stomach cold, pain in heart and abdomen, cough, asthma, excessive phlegm, deafness, pharyngitis, rheumatalgia, numbness of limbs, amenorrhea, and carbuncle. The bibliography: ' the main shooting and the grumpy are not constant, and the pill is taken; or pounding into powder, and mixing with vinegar. "Rihuazi": for wind-toxin swelling and paralysis, it is ground with vinegar and applied; removing blood stasis, relieving lumbago and kidney cold, and mixing with rhizoma Zingiberis recens, grinding, and applying; heart pain is caused by drinking wine and vinegar. "compendium" (compendium): warming the middle energizer to dispel cold, eliminating phlegm and benefiting orifices. For cough due to lung cold, wind-cold and pain in the stomach, vomiting of food, vomiting of lung cold, trismus and tight lips, abscess and swelling and blood stasis. "Classification of herb Properties": to induce sweating and dispel cold, warm the middle-jiao and stimulate the appetite, promote qi and eliminate phlegm, alleviate pain and reduce swelling. The composition is used together with semen Brassicae Junceae as semen Brassicae Junceae medicine. Semen Sinapis Albae is pungent and warm in flavor, enters lung and stomach channels, has effects of activating qi-flowing and eliminating phlegm, warming spleen and stomach for dispelling cold, dredging collaterals and relieving pain, and can be used for treating phlegm retention cough and asthma, fullness and pain in chest and hypochondrium, regurgitation emesis, apoplexy, numbness of limbs, loempe, dorsal furuncle, toxic swelling, and traumatic injury with swelling and pain.

Modern research shows that: the main components of the white mustard seed: sinapine (Sinalbin) about 2.5%, and contains fatty oil 20-26%, myrosinase (Myrosin), Sinapine (Sinapine), etc. The sinapine is enzymolyzed to generate p-hydroxybenzyl isothiocyanate (i.e. white mustard oil), acidic sinapine and glucose; the acidic sinapine sulfate is subjected to alkaline hydrolysis to generate sinapinic acid (Sinapic acid) and choline. The main components of the yellow mustard seed: sinapine (Sinigrin) is about 4%, and contains small amount of myrosinase, sinapic acid, sinapine and 30-37% of fatty oil, protein and mucus. The fatty oil is mainly Erucic acid (Erucic acid), 20-carbene-11 acid (eicosenoic acid), oleic acid, linoleic acid, arachidic acid and linoleic acid, palmitic acid, stearic acid, glyceryl ester of Behenic acid (Behenic acid), etc. The mustard oil contains methyl ester, isopropyl ester, allyl ester, butyl ester, sec-butyl ester, butene-3-ester, pentene-4-ester, phenyl ester, phenethyl ester and 3-methylthio propyl ester of isothiocyanate. The pre-test shows that the sample has the reaction of amino acid, protein, sugar, polysaccharide or glycoside, flavonoid glycoside, alkaloid, phytosterol, volatile oil, fatty oil and isothiocyanate glycoside. The research on the pharmacological action of the white mustard seed mainly focuses on 4 aspects of inhibiting the hyperplasia of prostate, resisting inflammation and easing pain, relieving cough, eliminating phlegm and relieving asthma and promoting transdermal absorption; in clinic, the white mustard seed can treat myopia by external pressure, pneumonia and bronchial asthma by external application, and can treat various inflammations and relieve various pains by oral administration. Semen Sinapis Albae has effects of relieving gout inflammation and relieving pain.

Kudzu root (yun gen-seng): pueraria edulis Pamp. The product is dried root of edible Pueraria lobata Ohwi of Leguminosae. The edible kudzu root (Pueraria edulis) contains allantoin, tetracosanoic acid-alpha-glyceride, beta-sitosterol, daidzein, genistin, daidzin, puerarin, daidzein-8-C-apiose (1 → 6) and glucoside in the literature report. Nature and taste: sweet in flavor and slightly cold in nature. Meridian tropism: enter yangming meridians. The functional indications are as follows: treating deficiency of flavor, diabetes, cold, summer-heat, typhoid, exterior pathogen, alternating cold and heat, damp malaria, and heat toxin in middle-jiao. The primary herb for the initial outbreak of infantile pox rash; relieving muscles and fever, promoting fluid production, promoting eruption, invigorating yang and relieving diarrhea; can be used for treating epidemic febrile disease, fever, headache, stiff neck, polydipsia, diarrhea, dysentery, measles without adequate eruption

Herba lophatheri: lophatherum gracile Brongn. The product is the whole herb of Lophatherum gracile of Gramineae, with stem and leaf similar to bamboo, and has light taste. Nature and taste: sweet, bland and cold. Meridian tropism: enter the heart, stomach, kidney and small intestine meridians. The functional indications are as follows: clearing away heart-fire, relieving restlessness, clearing away heat and toxic material, inducing diuresis for treating stranguria, and clearing away heat-phlegm. Compendium of materia Medica: lophatherum gracile, which is wild everywhere, high in size of spring seedlings, has thin stem and green leaves, and is like the basal leaves of thin bamboo grown on the ground of bamboo rice, which are rooted in a nest with tens of fibrous roots, but hard and mild in shape, like Mai Dong. Eighty and september stem, small and long spike, root seedling picked by human, pounded juice and rice as distiller's yeast, which is very fragrant. ' relieve dysphoria with smothery sensation, promote urination and clear away the heart-fire. Raw herb property for use: to clear phlegm and quench thirst, remove upper-jiao fire, improve eyesight, promote urination, treat whitish and turbid urine, defervesce and dispel hemorrhoid and sore toxicity. "

Modern research shows that: the main components of the lophatherum gracile are as follows: stem and leaf contain triterpene compounds: arundo donax, imperatorin, taraxacin, friedelin. The pharmacological action is as follows: 1. the antipyretic effect is as follows: animal experiment shows that the product has antipyretic effect on artificially febrile white rat through taking 1-20 g/kg Lophatherum gracile, and the components are dissolved in water and dilute acid and insoluble in alcohol and ether. 2. The diuretic effect is: clinical observation shows that the diuresis of Lophatherum gracile is weaker than that of Polyporus umbellatus. But promotes the chloride discharge in urine to be stronger than that of the polyporus umbellatus.

Rhizoma polygonati has the effects of strengthening spleen and tonifying kidney, can treat deficiency of both spleen and stomach, and is a monarch drug; the Chinese holly leaf can nourish liver and stomach, can treat liver and kidney yin deficiency, and is a ministerial drug; the lily has the effects of tonifying middle-jiao and Qi, clearing away heat and toxic materials, and clearing damp-heat in spleen and stomach and damp-heat in lower energizer as ministerial drugs; the corn stigma has the effects of promoting urination and reducing swelling as a ministerial drug; the kudzuvine root has the effects of relieving muscles and skin, relieving restlessness, quenching thirst and clearing away heat and toxic materials as ministerial drugs; lophatherum gracile has the effects of clearing away heart-fire and relieving restlessness, clearing away heat and toxic materials, inducing diuresis for treating stranguria, and clearing and resolving heat-phlegm as ministerial drugs. The warm and spicy nature of the yellow mustard seed can eliminate phlegm, dissipate stagnation, dredge collaterals and relieve pain, and is taken as an adjuvant drug. The truffle has the effects of supporting yang, regulating endocrine, enhancing immunity, resisting aging, resisting fatigue and the like; in the records of modern practical traditional Chinese medicines, rhizoma polygonati is used for intermittent fever, gout and periostitis; lily reduces the deposition of uric acid crystals and the inflammatory reaction by reducing the activity and phagocytosis of leucocytes and reducing the formation of lactic acid; puerarin can inhibit the generation of uric acid by inhibiting xanthine oxidase activity, increase the solubility of uric acid in urine, and maintain a certain excretion amount, thereby inhibiting the rise of blood uric acid level of organism, and is beneficial to improving the health condition of hyperuricemia patients; the corn stigma flavone relieves the acute inflammatory reaction of acute gouty arthritis and reduces the uric acid level by inhibiting the generation and release of inflammatory mediator factors; the coix seeds can inhibit reabsorption of uric acid by renal tubules and increase excretion of uric acid; sinigrin can inhibit capillary permeability and inflammatory exudation, and has antiinflammatory effect. The compatibility of the medicines has the effects of strengthening spleen and kidney, clearing heat and promoting diuresis.

Drawings

FIG. 1 is a schematic process flow diagram of a method of preparing a pharmaceutical composition of the present invention;

fig. 2 is a process flow diagram of the preparation method of the present invention.

Detailed Description

The present invention is further illustrated by the following examples, which are not intended to be limiting in any way, and any modifications or alterations based on the teachings of the present invention are intended to fall within the scope of the present invention.

The pharmaceutical composition comprises, by weight, 0.1-99 parts of rhizoma polygonati, 0.1-99 parts of Chinese holly leaf, 0.1-99 parts of lily, 0.1-99 parts of coix seed, 0.1-99 parts of corn stigma, 0.1-99 parts of kudzu root, 0.1-99 parts of lophatherum gracile and 0.1-99 parts of mustard seed, and is prepared by the steps of pretreatment, extraction, post-treatment, subpackage and the like.

The pharmaceutical composition comprises, by weight, 5-30 parts of rhizoma polygonati, 2-22 parts of Chinese holly leaf, 5-30 parts of lily, 5-30 parts of coix seed, 5-30 parts of corn stigma, 2-20 parts of semen brassicae, 2-20 parts of radix puerariae and 2-20 parts of lophatherum gracile, and is prepared by the steps of pretreatment, extraction, post-treatment, split charging and the like.

The preparation method of the pharmaceutical composition comprises the steps of pretreatment, extraction, post-treatment and subpackage, and specifically comprises the following steps:

A. pretreatment: weighing the raw materials according to the composition ratio, and crushing the raw materials and sieving the crushed raw materials by a sieve of 20-100 meshes for later use;

B. extraction: mixing the processed raw material medicines of Chinese holly leaf, kudzu root and yellow mustard seed, soaking the mixture for 2 to 4 hours by using 60 to 90 percent ethanol, adding 70 percent ethanol which is 15 to 18 times of the total weight of the raw materials for the first time, extracting the mixture for 80 minutes by using an ultrasonic method, adding 8 to 10 times of 70 percent ethanol for the second time, performing ultrasonic treatment for 40 minutes, combining filtrates, filtering, concentrating under reduced pressure until the relative density is between 1.05 and 1.18, adding 0.02 to 0.08 percent chitosan for clarification, standing for more than 24 hours, filtering to obtain a supernatant, concentrating under reduced pressure until the relative density is more than 1.30, and drying the supernatant to obtain a dry extract;

C. extraction: mixing the pretreated rhizoma polygonati, lily, lophatherum gracile, coix seed and corn stigma, soaking the mixture for 24 hours by using 15 times of water, supplementing the water absorption amount, decocting for 2 hours for the first time, adding 10 times of water for each decocting for 1 hour for the second time and the third time, combining the decoctions for three times, filtering, concentrating under reduced pressure until the relative density is 1.15-1.20, adding 0.03-0.06% of ZTC for clarification, standing for more than 12 hours, centrifuging, taking supernatant, concentrating under reduced pressure until the relative density is more than 1.30, and drying to obtain dry extract;

D. preparation: mixing the two dry extracts, pulverizing, sieving with 80-100 mesh fine powder, adding sieved maltose and lactose, mixing, making tea, drying, and packaging to obtain the final product.

B. And C, the water content of the dry extract of the dried medicinal composition in the step C is 5-7%.

The extraction is percolation extraction, reflux extraction, decoction extraction, ultrasonic extraction or microwave extraction.

Preparation method of dry extract of alcohol extract part of pharmaceutical composition for treating gout

Percolating for extraction

Pulverizing folium Ilicis Cornutae, radix Puerariae and semen Brassicae Junceae into coarse powder, mixing, soaking with 60-90% ethanol for 2-4 hr, adding 70% ethanol 15-18 times of the total weight of the raw materials, collecting percolate at 1-3ml/kg speed, and extracting effective components; collecting percolate and concentrating until the material-liquid ratio is 1: 6, adding 0.02-0.08% of chitosan for clarification, standing for more than 24h, filtering to obtain supernatant, concentrating under reduced pressure until the relative density is more than 1.30, and drying to obtain dry extract;

reflux extraction

Pulverizing folium Ilicis Cornutae, radix Puerariae and semen Brassicae Junceae into coarse powder, mixing, soaking with 60-90% ethanol for 2-4h, adding 8-12 times of 30-70% ethanol, soaking for 2-4h, supplementing water according to water absorption rate before refluxing, refluxing for 1-2h for the first time, adding 8 times of ethanol for refluxing for 0.5-1h for the second and third times, filtering, mixing filtrates, and concentrating until the ratio of material to liquid is 1: clarifying with 0.03-0.06 ‰ clarifier ZTC, keeping the temperature at 40-60 deg.C for 20-60min, standing at below 10 deg.C overnight, filtering to obtain supernatant, concentrating under reduced pressure to relative density of above 1.30, and drying to obtain dry extract;

micro-extraction method

Pulverizing folium Ilicis Cornutae, radix Puerariae and semen Brassicae Junceae into coarse powder, mixing, soaking in 3-5 times of 30-90% ethanol for 2-4h, supplementing ethanol before extraction according to water absorption rate, performing microwave extraction for 10-40min for the first time, performing microwave extraction for 10-30min for the second time with 3-5 times of ethanol, filtering, recovering ethanol under reduced pressure, and concentrating until the ratio of materials to liquids is 1: 5, clarifying with 0.3-0.6% of diatomite, preserving heat at 40-60 ℃ for 20-60min, standing overnight at the temperature of below 10 ℃, filtering to obtain supernatant, concentrating under reduced pressure until the relative density is above 1.30, and drying to obtain dry extract;

ultrasonic extraction

Pulverizing Chinese holly leaf, kudzu vine root and yellow mustard seed into coarse powder, mixing, infiltrating with 60-90% ethanol for 2-4h, adding 70% ethanol 15-18 times of the total weight of the raw materials for the first time, extracting for 80min by an ultrasonic method, adding 70% ethanol 8-10 times of the total weight of the raw materials for the second time, performing ultrasonic treatment for 40min, combining filtrates, filtering, concentrating under reduced pressure to a relative density of 1.05-1.18, adding chitosan 0.02-0.08%, clarifying, standing for more than 24h, filtering to obtain a supernatant, concentrating under reduced pressure to a relative density of more than 1.30, and drying to obtain a dry extract;

second, preparation method of dry extract of water extract part of pharmaceutical composition for treating gout

Reflux extraction

Mixing the pretreated rhizoma Polygonati, Bulbus Lilii, Coicis semen, folium Bambusae and stigma Maydis, soaking in 10-15 times of water for 12-24 hr, supplementing water absorption, refluxing for 1-2 hr for the first time, refluxing for 0.5-1 hr for the second and third times respectively with 8-10 times of water, filtering, mixing the filtrates, concentrating to relative density of 1.01-1.07, filtering, adding 0.03-0.06 ‰ chitosan, and stirring. Standing for more than 24 hr, collecting supernatant, filtering, concentrating the filtrate under reduced pressure to obtain fluid extract, and further concentrating to obtain dry extract.

Extracting by decocting

Mixing the pretreated rhizoma polygonati, lily, coix seed, lophatherum gracile and corn stigma, soaking the mixture for 12-24 hours by using 10-15 times of water, supplementing water absorption, decocting for 2 hours for the first time, adding 10-12 times of water for each decocting for 1 hour for the second time and the third time, combining the decoctions for three times, filtering, concentrating under reduced pressure until the relative density is 1.15-1.20, adding 0.03-0.06% of ZTC for clarification, standing for more than 12 hours, centrifuging to obtain a supernatant, concentrating under reduced pressure until the relative density is more than 1.30, and drying to obtain a dry extract;

ultrasonic extraction

Mixing the pretreated rhizoma polygonati, lily, coix seed, lophatherum gracile and corn stigma, soaking the mixture in 10-15 times of water for 12-24 hours, supplementing the water absorption amount, adding 15-18 times of water of the total weight of the raw materials, extracting the mixture for 80 minutes by an ultrasonic method, adding 8-10 times of water for ultrasonic treatment for 40 minutes for the second time, combining the filtrates, filtering, concentrating under reduced pressure until the relative density is 1.05-1.18, adding 0.02-0.08% of chitosan for clarification, standing for more than 24 hours, filtering to obtain a supernatant, concentrating under reduced pressure until the relative density is more than 1.30, and drying to obtain a dry extract;

microwave extraction

Mixing the pretreated rhizoma polygonati, lily, coix seed, lophatherum gracile and corn stigma, soaking the mixture for 12-24 hours by using 10-15 times of water, supplementing water according to the water absorption rate before extraction, performing microwave extraction for 10-40min for the first time, performing microwave extraction for 10-30min by adding 8-10 times of water for the second time, filtering, and concentrating until the material-liquid ratio is 1: 5, clarifying with 0.3-0.6% of diatomite, preserving heat at 40-60 ℃ for 20-60min, standing overnight at the temperature of below 10 ℃, filtering to obtain supernatant, concentrating under reduced pressure until the relative density is above 1.30, and drying to obtain dry extract;

the pharmaceutical composition for treating gout of the invention can be added with the following auxiliary materials: medicinal clarifying agent, excipient, solvent, antiseptic, and pH regulator.

A clarifying agent: chitosan, production unit: qingdao latent bioengineering, Inc.; diatomite: filter aid factory, tengcong county, Yunnan province; preservative: eucalyptus oil;

excipient: gelatin, glycerol, dextrin, starch, silicon dioxide, magnesium stearate, microcrystalline cellulose, sodium carboxymethyl cellulose, ethyl cellulose, hydroxypropyl cellulose, polyethylene glycol, polyvinylpyrrolidone and tween-80.

Solvent: vegetable oil (eucalyptus oil, peanut oil, rapeseed oil, walnut oil), glycerol, propylene glycol, liquid paraffin, and Cera flava; and (5) purifying the water.

Preservative: salicylic acid, benzoic acid and its sodium salt, methyl, ethyl, propyl, butyl (parabens), eucalyptus oil.

pH regulator: hydrochloric acid, acetic acid, citric acid, disodium hydrogen phosphate and sodium dihydrogen phosphate.

The amount of the added clarifying agent, excipient, solvent, preservative and pH regulator is carried out according to the requirement of medicinal standard.

The preparation of the pharmaceutical composition is prepared by adding pharmaceutically acceptable auxiliary materials into the pharmaceutical composition to prepare granules, tablets, capsules, soft capsules, dripping pills and the like.

The preparation method of the granules for treating gout comprises the following steps: pulverizing the dry extract, sieving with 80-100 mesh sieve, mixing with adjuvants such as starch, dextrin, silica gel micropowder, carboxymethyl cellulose-Na, magnesium stearate, etc., granulating, drying, grading, and packaging.

The preparation method of the tablet for treating gout comprises the following steps: pulverizing the dry extract, sieving with 80-100 mesh sieve, weighing adjuvants such as glidant, binder, and filler, mixing, granulating, drying, and tabletting.

The preparation method of the capsule agent for treating gout comprises the following steps: pulverizing the dry extract, sieving with 80-100 mesh sieve, mixing with silicon dioxide, magnesium stearate, microcrystalline cellulose, and ethyl cellulose, granulating, grading, and filling into hard capsule or enteric capsule. The preparation method comprises pulverizing the dry extract, sieving with 200 mesh sieve, granulating with hydroxypropyl cellulose, drying, grading, placing the capsule in a coating machine, adding ethanol solution of polyethylene glycol and ethyl cellulose to make into microcapsule, and filling into hard capsule or making into tablet.

The preparation method of the soft capsule for treating gout comprises the following steps: pulverizing the dry extract, sieving with 200 mesh sieve, mixing with adjuvants such as polyethylene glycol, gelatin, glycerol, and water, and making into soft capsule;

the preparation method of the dripping pill for treating gout comprises the following steps: pulverizing the dry extract, sieving with 200 mesh sieve, mixing with adjuvants such as polyethylene glycol and glycerol, and making into dripping pill.

The medicinal composition formula for treating gout has the advantages of unique curative effect, small side effect and no toxic or side effect, can prevent and treat gout caused by high uric acid, and has better curative effect.

The invention is further illustrated below with reference to specific embodiments:

the following specific embodiment scheme is shown in figure 1;

example 1

Soaking 18 parts of Chinese holly leaf, 20 parts of kudzu root and 15 parts of yellow mustard seed in 75% ethanol for 2-4 hours, adding 18 times of ethanol of the total weight of the raw materials for the first time, extracting for 80 minutes by an ultrasonic method, adding 10 times of 75% ethanol for the second time, carrying out ultrasonic treatment for 40 minutes, combining filtrates, filtering, concentrating under reduced pressure until the relative density is 1.13, adding 0.05% chitosan for clarifying, standing for 24 hours, filtering to obtain a supernatant, concentrating under reduced pressure, and drying to obtain a dry extract; mixing with 32 parts of rhizoma Polygonati, 18 parts of Bulbus Lilii, 25 parts of Coicis semen, and 30 parts of stigma Maydis water extract, making into granule, and packaging.

Example 2

Soaking 18 parts of Chinese holly leaf, 15 parts of kudzu root and 20 parts of yellow mustard seed in 80% ethanol for 6-8 hours, adding 20 times of ethanol in total weight of raw materials for the first time, extracting for 2 hours by a reflux method, adding 15 times of 80% ethanol for the second time, refluxing for 1 hour, combining filtrates, filtering, concentrating under reduced pressure until the relative density is 1.20, adding 0.08% chitosan, clarifying, standing for 24 hours, filtering to obtain a supernatant, concentrating under reduced pressure, and drying to obtain a dry extract; mixing with 32 parts of rhizoma Polygonati, 18 parts of Bulbus Lilii, 25 parts of Coicis semen, and 30 parts of stigma Maydis water extract, making into granule, and packaging.

Example 3

Weighing 28 parts of rhizoma polygonati, 15 parts of lily, 20 parts of semen coicis, 15 parts of lophatherum gracile and 28 parts of corn stigma, soaking for 12 hours by using 15 times of water, supplementing water absorption, decocting for 2 hours for the first time, adding 8 times of water for each decocting for 1 hour for the second time and the third time, combining the decoctions for three times, filtering, concentrating under reduced pressure until the relative density is 1.17, adding 0.04% of ZTC for clarification, standing for more than 12 hours, centrifuging to obtain a supernatant, concentrating under reduced pressure until the relative density is more than 1.32, and drying to obtain a dry extract; mixing with 20 parts of folium Ilicis Cornutae and 18 parts of semen Brassicae Junceae, extracting with 70% ethanol, making into hard capsule, and packaging.

Example 4

Weighing 28 parts of rhizoma polygonati, 15 parts of lily, 15 parts of lophatherum gracile, 20 parts of semen coicis and 28 parts of corn stigma, soaking for 15 hours by using 20 times of water, supplementing water absorption, decocting for 4 hours for the first time, decocting for 2 hours by adding 12 times of water for the second time and the third time respectively, combining the decoctions for three times, filtering, concentrating under reduced pressure until the relative density is 1.20, adding 0.08% ZTC for clarification, standing for more than 24 hours, centrifuging to obtain a supernatant, concentrating under reduced pressure until the relative density is more than 1.20, and drying to obtain a dry extract; mixing with 20 parts of folium Ilicis Cornutae and 18 parts of semen Brassicae Junceae, extracting with 70% ethanol, making into hard capsule, and packaging.

Example 5 embodiments of gout control granules

Example 6 hard capsule for the prevention and treatment of gout

Example 7 embodiments of enteric capsules for the prevention and treatment of gout

Example 8 implementation scheme of gout prevention and treatment drop pills

Example 9 embodiments of gout control tablets

Example 10 embodiments of Soft capsules for the prevention and treatment of gout

Example 11 embodiments for the prevention and treatment of gout (decoction)

Example 12 embodiments of gout control film coated tablets

The first experimental example: the pharmaceutical composition for preventing and treating gout, disclosed by the invention, is applied to clinical trial research on preparation of medicines for preventing and treating gout caused by weakness of spleen and stomach

First, research object

1. Source of case

The patients are diagnosed in XX clinics from 1 month to 12 months in 2018 to 2019, and are clinically diagnosed as the spleen-kidney deficiency syndrome of chronic uric acid nephropathy.

2. Diagnostic criteria

(1) Standard of Western diagnosis

Refer to Wang Hai Yan's third edition "Shen Bing Bian Xuan (nephrology), 2011" clinical diagnosis and treatment guide-Kidney Bing Bian "(partial book for nephrology); 2008 Chinese medical science institute of nephropathy division "diagnosis, syndrome differentiation, typing and efficacy assessment of uric acid nephropathy".

(2) Chinese medicine syndrome diagnosis standard and integral standard

According to the diagnosis, syndrome differentiation and type classification and curative effect evaluation of uric acid nephropathy of the nephrosis division of Zoos Chinese traditional medicine society; the grading and quantification standard of common symptoms is based on the nephropathy division of the Chinese medical science society of 2008 "diagnosis, syndrome differentiation, typing and treatment effect assessment of uric acid nephropathy".

3. Inclusion criteria

(1) Age 20-75 years;

(2) meets the diagnosis standard of chronic uric acid nephropathy and spleen-kidney qi deficiency syndrome.

4. Exclusion criteria

(1) Pregnant, lactating or planned to become pregnant, under the age of 20 or over the age of 75, with traditional Chinese medicines and people with a particular "chacha" allergy;

(2) removing urinary nephropathy caused by lypocoma, myeloma, hematopathy, malignant tumor radiotherapy and chemotherapy, severe psoriasis, Snake worm diuretic, cytotoxic drug, hypothyroidism, lead poisoning, etc., and uric acid nephropathy caused by lack of hereditary hypoxanthine phosphoribosyl transferase; the uric acid reducing medicine is taken before the patients are put into the group;

(3) acute kidney disease, nephrotic syndrome, dialysis or kidney transplantation, acute liver injury, chronic liver injury (ALT and AST greater than twice the upper limit of the reference range), diabetes;

(4) estrogen replacement therapy;

(5) if the patient does not meet the inclusion standard and is not administered according to the prescription, the patient can not judge the curative effect or the data is incomplete and the like to influence the judgment of the curative effect;

(6) for those with factors causing transient reversible decline of renal function, such as uncontrolled hypertension, excessive intake of protein, severe infection, wound, application of medicine for kidney damage, urinary tract obstruction, and blood volume deficiency;

(7) other drugs that affect kidney function were taken during the observation period.

5. Rejection and shedding criteria

(1) Cases where subjects self-exited;

(2) poor subject compliance, non-compliant;

(3) cases in which severe adverse events, complications and specific physiological changes occur and are not suitable for further study;

6. abort criterion

If the blood uric acid of men exceeds 773.5umol/L (13mg/dl) and the blood uric acid of women exceeds 595umo1/L (10mg/dl) for 2 months, the administration is stopped from the clinical test, and febuxostat is administered according to the liver and kidney functions of the patients to reduce the blood uric acid.

Second, research method

1. Case collection

60 patients with chronic uric acid renal disease who meet the inclusion standard are collected.

2. Random blind method design

The random double-blind design gives the patients a natural number from 1 to 60 in the sequence of treatment, and the corresponding numbers generated by excel are randomly divided into 2 groups, namely a traditional Chinese medicine group and a western medicine group, wherein each group contains 30 bits.

Third, treatment course

1. The treatment period is 3 months;

2. criteria for therapeutic effect

The standard for judging the curative effect of clinical diseases refers to the guidance principle of clinical research on new Chinese medicines in 2002;

3. criteria for determining the therapeutic effects of clinical syndromes

Refer to 2002 "clinical research guidelines for new drugs of Chinese medicine";

4. method of administration

(1) Treatment groups: allopurinol is orally taken, 100mg per tablet, 100mg each time and three times per day;

(2) experimental groups: prepared as in example 5, orally administered 10g each time three times a day.

Fourth, experiment detection method

1. Reagent and apparatus

Uric acid kit (batch: 20160102), Shenzhen Merrill biomedical electronics, Inc.; chloral hydrate 10% (batch: 20160512), Qingdao-Ixong algae Co. LD4 model low speed centrifuge, beijing medical centrifuge factory; AU640 full-automatic biochemical analyzer, Olympus, Japan.

2. Preparation of specimens all subjects collected cubital venous blood on an empty stomach at 7:00-7:30 am, wherein blood was drawn 1 time each on the day of treatment initiation and the morning of the 1 st, 2 nd and 3 rd months after initiation of treatment in the treatment group and the experimental group.

3. Statistical treatment

Performing data analysis and statistical processing by using SPSS 13.0 software; the metrology data is expressed in terms of "mean squared error" (X S). The comparison between the measurement data groups adopts independent sample t test, and the comparison between the groups before and after treatment adopts paired sample t test. Ridit analysis is adopted for grade data; the difference was significant with P < 0.05.

5. Main indexes

(1) Determining the uric acid level at the end of each month, as compared to pre-dose;

(2) number of joint pain, number of joint swelling;

(3) pain lOcm level visual contrast scale (VAS) test.

6. Secondary index

(1) Traditional Chinese medicine syndrome score (see tables 1 and 2);

(2) comparing the clinical effects before and after treatment;

(3) number of relapses of acute gouty arthritis.

TABLE 1

TABLE 2

Fifth, improvement analysis of therapeutic index

1. Uric acid improvement

Table 3: comparison of uric acid improvement before and after treatment

Unit: umol/L

Group of	Number of examples	Before treatment	After taking for 1 month	2 months after administration	After 3 months of administration
						Treatment group	30	498.45±71.01	436.46±89.63	355.60±90.88	277.23±53.38
Experimental group	30	535.90±108.90	482.00±129.12	398.34±63.03	256.44±42.32

And (3) analyzing an experimental result: (1) group control: p is less than 0.01 in the first month, the second month and the third month before and after treatment in the treatment group, which indicates that the groups have very significant difference; in the experimental group, P is less than 0.01 in the first month, the second month and the third month before and after treatment, which indicates that the groups have significant difference. (2) Control between groups: the experimental group and the control group before treatment have P >0.05, which indicates that the two groups have significant difference, and the P <0.05 after 1 month of treatment indicates that the two groups have significant difference; after two and three months of treatment, P <0.01, indicating a very significant difference between the two groups.

2. Improvement of painful joint count

Table 4: improvement of painful joint counts before and after treatment

Group of	Number of examples	Before treatment	After 3 months of administration
				Treatment group	30	3.12±2.52	1.12±0.81
Experimental group	30	3.30±2.42	0.73±0.58

And (3) analyzing an experimental result: (1) group control: p is less than 0.01 in the treatment group before treatment and after the third month of treatment, which indicates that the groups have very significant difference; the P of the experimental group is less than 0.01 compared with the P of the experimental group after the third month of treatment, which indicates that the groups have significant difference. (2) Control between groups: the P is greater than 0.05 in the experimental group and the control group before treatment, which indicates that the two groups have significant difference; p <0.01, compared before treatment and after the third month of treatment, indicates that there is a very significant difference between the two groups.

3. Improvement in swollen joint count

Table 5: improvement of swollen joint number of patients before and after treatment

Group of	Number of examples	Before treatment	After 3 months of administration
				Treatment group	30	1.14±0.94	0.92±0.10
Experimental group	30	1.21±0.99	0.39±0.14

And (3) analyzing an experimental result: (1) group control: p is less than 0.01 in the treatment group before treatment and after the third month of treatment, which indicates that the groups have very significant difference; the P of the experimental group is less than 0.01 compared with the P of the experimental group after the third month of treatment, which indicates that the groups have significant difference. (2) Control between groups: the P is greater than 0.05 in the experimental group and the control group before treatment, which indicates that the two groups have significant difference; p <0.01, compared before treatment and after the third month of treatment, indicates that there is a very significant difference between the two groups.

4. Pain VAS score improvement before and after treatment

Table 6: pain VAS score improvement before and after treatment

Group of	Number of examples	Before treatment	After 3 months of administration
				Treatment group	30	2.84±1.67	0.58±0.24
Experimental group	30	2.94±1.75	0.61±0.35

And (3) analyzing an experimental result: (1) group control: p is less than 0.01 in the treatment group before treatment and after the third month of treatment, which indicates that the groups have very significant difference; the P of the experimental group is less than 0.01 compared with the P of the experimental group after the third month of treatment, which indicates that the groups have significant difference. (2) Control between groups: the P is greater than 0.05 in the experimental group and the control group before treatment, which indicates that the two groups have significant difference; p <0.01, compared before treatment and after the third month of treatment, indicates that there is a very significant difference between the two groups.

5. Improving condition of traditional Chinese medicine syndrome score before and after treatment

Table 7: improving condition of traditional Chinese medicine syndrome score before and after treatment

Group of	Number of examples	Before treatment	After 3 months of administration
				Treatment group	30	10.37±5.90	3.50±2.40
Experimental group	30	11.98±6.12	3.63±3.52

And (3) analyzing an experimental result: (1) group control: p is less than 0.01 in the treatment group before treatment and after the third month of treatment, which indicates that the groups have very significant difference; the P of the experimental group is less than 0.01 compared with the P of the experimental group after the third month of treatment, which indicates that the groups have significant difference. (2) Control between groups: the P is greater than 0.05 in the experimental group and the control group before treatment, which indicates that the two groups have significant difference; p <0.01, compared before treatment and after the third month of treatment, indicates that there is a very significant difference between the two groups.

6. Comparison of clinical efficacy before and after treatment

Table 8: comparison of clinical efficacy before and after treatment

And (3) analyzing an experimental result: ridit analysis shows that 95% of straight line intervals are (0.5029,0.8458) and P is less than 0.05, which indicates that the two groups have significant difference, and the R value of the experimental group is greater than that of the treatment group, thereby proving that the experimental group is superior to the treatment group.

7. Patient relapse rate and relapse factors during treatment:

(1) the recurrence rate is: the recurrence rate in the treatment group was between 25% and the recurrence rate in the experimental group was between 15%.

(2) Recurrence factors: the main factors are trauma, such as: cold, strain, sprain, etc.; second, fatigue, diet intolerance and other factors, such as: fatigue driving, sedentariness, irregular work and rest, and the like, and seafood, viscera, beer and the like are eaten.

Claims (8)

1. The pharmaceutical composition for treating gout is characterized by comprising, by weight, 5-30 parts of rhizoma polygonati, 2-22 parts of Chinese holly leaf, 5-30 parts of lily, 5-30 parts of semen coicis, 5-30 parts of corn stigma, 2-20 parts of semen brassicae, 2-20 parts of radix puerariae and 2-20 parts of lophatherum gracile, and is prepared by the steps of pretreatment, alcohol extraction, water extraction and post-treatment.

2. The pharmaceutical composition of claim 1, wherein:

the medicinal composition comprises 15 parts of rhizoma polygonati, 12 parts of Chinese holly leaves, 15 parts of lily, 15 parts of coix seeds, 15 parts of corn stigma, 8 parts of yellow mustard seeds, 10 parts of kudzu roots and 10 parts of lophatherum gracile according to the weight ratio of the raw materials;

the preparation method comprises the following steps of pretreatment, extraction and post-treatment:

A. the pretreatment: weighing and crushing the raw materials according to the composition ratio for later use;

B. and (3) alcohol extraction: mixing the pretreated Chinese holly leaf, kudzu root and yellow mustard seed, soaking the mixture for 2-4 hours by using 60-90% ethanol, adding 70% ethanol which is 15-18 times of the total weight of the raw materials for extraction for 80 minutes for the first time, adding 70% ethanol which is 8-10 times of the total weight of the raw materials for extraction for 40 minutes for the second time, combining filtrates, filtering, concentrating under reduced pressure until the relative density is 1.05-1.18, adding 0.02-0.08% chitosan for clarification, standing for more than 24 hours, filtering to obtain a supernatant, concentrating under reduced pressure until the relative density is more than 1.30, and drying to obtain a dry extract;

C. the water extraction: mixing the pretreated rhizoma polygonati, lily, coix seeds, corn stigma and lophatherum gracile, soaking the mixture for 24 hours by 15 times of water, supplementing the water absorption amount, decocting for 2 hours for the first time, adding 10 times of water for each decocting for 1 hour for the second time and the third time, combining the decoctions for three times, filtering, concentrating under reduced pressure until the relative density is 1.15-1.20, adding 0.03-0.06% of ZTC for clarification, standing for more than 12 hours, centrifuging, taking supernatant, concentrating under reduced pressure until the relative density is more than 1.30, and drying to obtain dry extract;

D. and (3) post-treatment: mixing the two dry extracts obtained by alcohol extraction and water extraction, crushing, sieving by 80-100 meshes of fine powder, adding screened maltose and lactose, uniformly mixing, preparing tea, drying and subpackaging to obtain the medicinal composition.

3. The pharmaceutical composition of claim 2, wherein the extraction method in the alcohol extraction is any one of percolation extraction, reflux extraction, decoction extraction, ultrasonic extraction and microwave extraction.

4. The pharmaceutical composition according to claim 1 or 2, further comprising an added pharmaceutical adjuvant, wherein the pharmaceutical adjuvant is: pharmaceutical clarifiers, excipients, solvents, preservatives, and/or PH modifiers.

5. A preparation of the pharmaceutical composition as claimed in any one of claims 1 to 4, wherein the pharmaceutical composition is added with pharmaceutically acceptable adjuvants to prepare granules, tablets, capsules, soft capsules or dripping pills.

6. The formulation of the pharmaceutical composition of claim 5, wherein:

the preparation method of the granules comprises the following steps: pulverizing the dry extract, sieving with 80-100 mesh sieve, mixing with adjuvants such as starch, dextrin, silica gel micropowder, carboxymethyl cellulose-Na, magnesium stearate, etc., granulating, drying, grading, and packaging;

the preparation method of the tablet comprises the following steps: pulverizing the dry extract, sieving with 80-100 mesh sieve, weighing adjuvants such as glidant, binder, and filler, mixing, granulating, drying, and tabletting;

the preparation method of the capsule comprises the following steps: pulverizing the dry extract, sieving with 80-100 mesh sieve, mixing with silicon dioxide, magnesium stearate, microcrystalline cellulose, and ethyl cellulose, granulating, grading, and filling into hard capsule or enteric capsule. The preparation method comprises pulverizing the dry extract, sieving with 200 mesh sieve, granulating with hydroxypropyl cellulose, drying, grading, placing the capsule in a coating machine, adding ethanol solution of polyethylene glycol and ethyl cellulose to make into microcapsule, and filling into hard capsule or tabletting;

the preparation method of the soft capsule comprises the following steps: pulverizing the dry extract, sieving with 200 mesh sieve, mixing with adjuvants such as polyethylene glycol, gelatin, glycerol, and water, and making into soft capsule;

the preparation method of the dripping pill comprises the following steps: pulverizing the dry extract, sieving with 200 mesh sieve, mixing with adjuvants such as polyethylene glycol and glycerol, and making into dripping pill.

7. The use of the pharmaceutical composition according to any one of claims 1 to 4, for preparing a medicament for preventing and treating gout caused by weakness of the spleen and stomach.

8. The use of the preparation of the pharmaceutical composition according to claim 5 or 6 for the preparation of a medicament for preventing and treating gout caused by weakness of the spleen and stomach.

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