Anti-hyperuricemia traditional Chinese medicine composition, preparation method of extract of anti-hyperuricemia traditional Chinese medicine composition, pharmaceutical composition and application

Abstract

The invention discloses a traditional Chinese medicine composition containing medicinal and edible medicinal materials such as chicory leaves, astragalus membranaceus, pawpaw and mango leaves, a pharmaceutical composition as well as a preparation method and application of the traditional Chinese medicine composition. The traditional Chinese medicine composition achieves the effect of reducing uric acid through the effects of inhibiting uric acid reabsorption and promoting uric acid excretion, and has an exact treatment effect on hyperuricemia. The medicinal material base source is stable, the medicine is safe and effective, clinical application is flexible, and different dosage forms can be prepared according to needs. The preparation process is stable and controllable and is easy to amplify.

Description

Technical Field

[0001] The present invention relates to a Chinese medicine composition for resisting hyperuricemia and a preparation method of an extract thereof, a pharmaceutical composition and an application thereof, and in particular to a Chinese medicine composition for resisting hyperuricemia which is both a medicine and a food, a preparation method of an extract thereof, a pharmaceutical composition and an application thereof. Background Art

[0002] Hyperuricemia (HUA) refers to an adult with a fasting blood uric acid level of more than 420 μmol / L twice on different days under a normal purine diet. In addition to idiopathic hyperuricemia, factors such as blood system tumors, chronic renal insufficiency, congenital metabolic abnormalities, poisoning, and drugs can also cause elevated blood uric acid levels. Elevated blood uric acid levels can cause gout, leading to the occurrence and development of kidney, endocrine metabolism, cardiovascular and cerebrovascular system diseases, and the treatment cycle is long, the control is complex, the disease is prone to recurrence, and the prognosis is poor, which has a serious impact on people's physical health and peace of life, especially hyperuricemia nephropathy, hyperuricemia cardiovascular disease, hyperuricemia diabetes, etc., which have directly endangered life.

[0003] When chemical drugs are used to treat hyperuricemia, whether it is to inhibit uric acid production, increase uric acid excretion, or assist in the treatment of both with alkalinized urine preparations, they all have certain toxic side effects and damage liver and kidney function. In particular, the medication cycle of these drugs is relatively long, and their toxic side effects and damage to liver and kidney function accumulate, which is harmful to human health. When biological agents are used to treat gouty arthritis, they are administered by subcutaneous injection or intravenous administration, which may cause adverse events such as local itching or infusion reactions, and may also cause abnormalities such as increased transaminase, decreased white blood cells, and positive antinuclear antibodies. When Chinese medicine is used to treat hyperuricemia, since hyperuricemia is a metabolic disease, the dialectical treatment of Chinese medicine is one prescription for one person, and the medication, ratio, and dosage vary from person to person. Even if there is a basic prescription, it must be added or subtracted according to the person when it is used; and the disadvantages of traditional Chinese medicine decoctions also bring a lot of inconvenience to patients. Summary of the invention

[0004] Purpose of the invention: The first purpose of the present invention is to provide a Chinese medicine composition for treating hyperuricemia, the second purpose is to provide a method for preparing an extract of the Chinese medicine composition, the third purpose is to provide a pharmaceutical composition containing the extract of the Chinese medicine composition, and the fourth purpose is to provide a pharmaceutical application of the Chinese medicine composition, its extract, and the pharmaceutical composition.

[0005] Technical solution: The anti-hyperuricemia Chinese medicine composition described in the present invention comprises, by weight, 10-40 parts of chicory leaves, 10-40 parts of astragalus, 4-20 parts of papaya, 4-20 parts of mango leaves, 2-10 parts of eucommia, 2-10 parts of daidai hua, 2-10 parts of galangal, 2-10 parts of gastrodia, 2-10 parts of toona sinensis leaves, 2-10 parts of emblica, 2-10 parts of coix seeds, 2-10 parts of yam, 2-10 parts of corn silk, 1-5 parts of poria, 1-5 parts of kaempferia and 1-4 parts of zanthoxylum bungeanum.

[0006] Preferably, the anti-hyperuricemia Chinese medicine composition of the present invention comprises, by weight, 15-30 parts of chicory leaves, 15-30 parts of astragalus, 6-10 parts of papaya, 6-10 parts of mango leaves, 3-7 parts of eucommia, 3-7 parts of daikon jasmine, 3-7 parts of galangal, 3-7 parts of gastrodia, 3-7 parts of toona sinensis leaves, 3-7 parts of emblica, 3-7 parts of coix seeds, 3-7 parts of yam, 3-7 parts of corn silk, 2-4 parts of poria, 2-4 parts of kaempferia galanga and 2-3 parts of zanthoxylum bungeanum.

[0007] Preferably, in parts by weight, the anti-hyperuricemia Chinese medicine composition of the present invention comprises 20 parts of chicory leaves, 20 parts of astragalus, 8 parts of papaya, 8 parts of mango leaves, 4 parts of eucommia, 4 parts of daidai hua, 4 parts of galangal, 4 parts of gastrodia, 4 parts of toona sinensis leaves, 4 parts of emblica, 4 parts of coix seeds, 4 parts of yam, 4 parts of corn silk, 3 parts of poria, 3 parts of kaempferia and 2 parts of Zanthoxylum bungeanum.

[0008] Traditional Chinese medicine believes that high uric acid is a series of diseases caused by heavy dampness, also known as pain and arthralgia or gout, which belongs to the category of arthralgia. Patients with high uric acid may not have obvious symptoms in the early stage. As uric acid increases and the disease progresses, patients will develop gout, and may also develop kidney stones, rheumatic nephropathy, etc. In the acute stage of gouty arthritis, the core syndrome is damp-heat accumulation syndrome, which is treated by clearing heat and removing dampness, reducing swelling and relieving pain. If the swelling and pain are prolonged and repeated, joint deformities, or accompanied by tophi and even ulceration, it is the chronic stage of gouty arthritis, and common syndromes include phlegm and blood stasis arthralgia syndrome, spleen deficiency and damp-heat syndrome, and spleen and kidney deficiency syndrome. Phlegm and blood stasis arthralgia syndrome is treated by resolving phlegm and removing blood stasis, removing arthralgia and unblocking collaterals; spleen deficiency and damp-heat syndrome is treated by invigorating qi and strengthening the spleen, clearing heat and removing dampness; spleen and kidney deficiency syndrome is treated by strengthening the spleen and benefiting the kidney. Different syndromes have different treatment methods and different prescriptions and medications. Although traditional Chinese medicine attributes hyperuricemia to arthritis, hyperuricemia is not necessarily gout, and the causes and pathologies of the two cannot be completely equated.

[0009] Traditional Chinese medicine also believes that the occurrence of gout is related to the invasion of exogenous evil, weak spleen and stomach, and irregular diet. For example, the influence of damp-heat or cold-damp evil turning into heat, blocking the meridians and joints and causing disease; weak spleen and stomach, abnormal transportation and transformation function of the human body leads to internal generation of dampness, which turns into heat over time and flows into the meridians and can also cause disease; liking to eat rich and greasy food damages the spleen and stomach, spleen deficiency generates dampness and heat, and dampness and heat block the meridians and cause disease.

[0010] The above theories all emphasize the function of spleen and stomach and spleen and kidney deficiency, but the present invention believes that there are also pathogenesis of liver depression and qi stagnation, liver depression and spleen deficiency, liver and kidney deficiency, and in the relationship between liver and spleen and liver and kidney, liver occupies a dominant position. The Chinese medicine composition of the present invention treats from the perspective of liver, adopts the treatment method of soothing liver and strengthening spleen and tonifying liver and kidney, which is the key to the treatment of hyperuricemia. The liver is a "hard organ" among the five internal organs. One of its main functions is to regulate qi and blood, and it has the functions of dredging, unblocking, and venting. The first is to regulate qi and blood and ensure the normal activities of various organs. If the liver qi is depressed and the qi is not smooth, qi stagnation and blood stasis will occur, which will affect the dysfunction of spleen and kidney. The second is to relieve emotions. If the liver qi is normal, the qi and blood will be peaceful and the functions will be coordinated. On the contrary, if it is excited or angry, the liver qi will be stagnant and the qi will be unregulated. The third is to strengthen the spleen and stomach and promote digestion. If the liver fails to regulate qi, there will be disharmony between the liver and stomach, and disharmony between the liver and spleen. "Seeing the liver disease, know that the liver transmits to the spleen"; the fourth is to clear the triple energizer and dredge the waterway. If the liver fails to regulate qi, the qi will be unblocked and blood stasis and yin stagnation will occur. It can be seen from this that if the liver is not good, it will affect the spleen and kidney; if the liver is stagnant (acid), toxins in the body cannot be excreted, which will inevitably lead to the inability of kidney water to be transported, the waterway is blocked, urine is abnormal, and uric acid accumulates.

[0011] Modern medicine believes that abnormal liver function can affect uric acid levels. This is because liver cell damage, cholestasis, uric acid metabolism disorders in the liver, drugs affecting liver function, and alcoholic liver disease may change the liver's ability to metabolize and excrete uric acid. First, when liver cells are damaged, their detoxification and secretion functions decline, resulting in a decrease in the liver's ability to process uric acid, which in turn leads to increased uric acid levels in the serum, and then causes diseases such as hyperuricemia or gout; second, when cholestasis occurs, bile excretion is blocked, which reversibly stimulates liver cells to synthesize more uric acid. At this time, not only will symptoms such as jaundice and itching appear, but also an increase in serum uric acid concentrations; third, when uric acid metabolism is impaired in the liver, it will cause the body's uric acid to be unable to be excreted normally, causing an increase in uric acid levels. This condition may increase the risk of gout, manifested as swollen joints. , pain and other symptoms; Fourth, some drugs (including drugs for the treatment of gout) may affect the metabolism of uric acid by interfering with the function of liver cells, such as phenobarbital tablets, lamivudine tablets, colchicine, allopurinol, etc. These drugs will increase the burden on liver function, cause liver cell damage, and further affect the metabolism of uric acid. Patients may experience nausea, vomiting, loss of appetite and other discomfort symptoms, and in severe cases may even cause liver failure; Fifth, the liver cells of patients with alcoholic liver disease are affected by long-term drinking and undergo pathological changes such as inflammation and necrosis, resulting in damaged liver function, including the metabolic function of uric acid. Patients may experience typical symptoms such as fatigue, fullness in the right upper abdomen, and loss of appetite. If not treated in time, the disease continues to develop and cirrhosis may occur.

[0012] In addition, the liver and kidneys affect each other. The liver is the main detoxification and metabolic organ of the human body, while the kidneys are the main excretion organs of the end products of metabolism. If the liver function is insufficient, there will be too many toxic substances in the metabolites, which will not only increase the burden on the kidneys, but also may cause direct damage to kidney function. Therefore, poor liver function may directly lead to the occurrence of kidney disease.

[0013] The Chinese medicine composition of the present invention treats hyperuricemia by treating the liver, kidney and spleen simultaneously, and attaches importance to the treatment principle of the liver.

[0014] The whole prescription targets the pathogenesis and symptoms of uric acid production and excretion, with chicory leaves and astragalus as the main drugs, papaya, mango leaves, eucommia, daidaihua, gastrodia, toona sinensis leaves, and emblica as the secondary drugs, galangal, coix seeds, yam, corn silk, and poria as the adjuvant drugs, and galangal and prickly ash as the guiding drugs. It has both offensive and defensive functions, both purgation and tonification, and both cold and heat are adjusted. It has the functions of soothing the liver and regulating qi, strengthening the spleen and removing dampness, and tonifying the kidney and promoting urination.

[0015] The main herb, chicory leaf, is cool in nature, slightly bitter and salty in taste, and enters the spleen, liver, and bladder meridians. It has the effects of clearing the liver and promoting bile secretion, and diuresis and swelling. Astragalus is sweet in taste and slightly warm in nature, and enters the spleen and lung meridians. It has the effects of strengthening the spleen and replenishing the middle, raising yang, and diuresis. The two main herbal medicines treat the liver to reduce acid, and strengthen the spleen to replenish the kidney. They have clear goals, support each other, and overcome acid numbness together. The two medicines are complementary, one attacking and one defending, one draining and one replenishing, complementing each other, jointly inhibiting uric acid production and promoting uric acid excretion. Moreover, chicory leaf is too bitter and cold, while Astragalus is warm and sweet. The two medicines merge with each other to resolve the bias and offset each other's deficiencies.

[0016] The ministerial drug papaya is sour and warm in nature. It belongs to the liver and spleen meridians. It is effective in removing dampness and relaxing muscles. It treats dampness, stiffness, soreness and pain in the waist and knee joints, and cramps. Here, the treatment of cramps is not to benefit the muscles, but to regulate the spleen and cut the liver. It is only because the earth disease causes the decline of metal and the prosperity of wood, so the sour and warm are used to collect the dissipation of the spleen and stomach, and to use it to move the muscles to calm the liver evil. Eucommia ulmoides is warm in nature, sweet and slightly spicy, and belongs to the liver and kidney meridians. It is effective in nourishing the liver and kidney and strengthening the muscles and bones. Mango leaves are mild in nature and slightly sour in taste. They belong to the spleen, lung, and stomach meridians, and their functions are to eliminate stagnation. Daidaihua is mild in nature, sweet in taste, slightly bitter, and belongs to the liver and stomach meridians. It has the effect of soothing the liver and regulating qi, harmonizing the stomach and relieving pain. Gastrodia elata is mild in nature and sweet in taste. It belongs to the liver meridian. It can not only remove external wind, but also dredge the meridians and relieve pain. In clinical practice, it is often used in combination with dispersing wind and cold drugs, tonic drugs, anti-rheumatic drugs, blood circulation and blood stasis drugs, and warming drugs to adjust its bias, enhance efficacy or reduce toxic reactions. Chinese yam is warm in nature and sweet in taste. It enters the lung, spleen, and kidney meridians and the blood of the hand and foot Taiyin meridians. It nourishes the spleen and stomach, promotes the production of body fluids, and nourishes the kidneys. Corn silk is flat in nature and sweet and light in taste. It enters the bladder, liver, and gallbladder meridians. It has the function of diuresis and swelling, and assists in clearing the liver and promoting bile secretion. The seven ministers focus on assisting in clearing the liver and soothing the liver, strengthening the spleen and nourishing the kidneys, and filling the omissions and stamina of the monarch medicine.

[0017] The adjuvant drug Alpinia officinalis is hot and pungent in taste, and it enters the spleen and stomach meridians. It has the effects of warming the stomach and stopping vomiting, dispelling cold and relieving pain. It is intended to assist in strengthening the spleen and kidney and eliminating the bias of cold and cool drugs. Toona sinensis leaves are neutral in nature, sweet, bitter and pungent in taste, and enter the heart, spleen and large intestine meridians, strengthen the stomach and reduce inflammation. Phyllanthus emblica is cool in nature, sweet, sour and astringent in taste, and enters the lung and stomach meridians, clears heat and cools blood, and helps digestion and strengthens the stomach. Coix seed is cool in nature, sweet and light in taste, and enters the spleen, stomach and lung meridians. It is effective in strengthening the spleen and eliminating dampness and removing numbness. Poria cocos is neutral in nature, sweet and light in taste, and enters the heart, lung, spleen and kidney meridians. It has the effects of diuresis and dampness, strengthening the spleen, and calming the mind to relieve the discomfort of the disease. The above five flavors jointly assist the monarch and ministerial drugs, or make up for the omissions, or strengthen the weaknesses, so as to ensure that the efficacy of the monarch and ministerial drugs is fully exerted.

[0018] The herb Kaempferia galanga is warm in nature, pungent in taste, and belongs to the stomach meridian. It has the effects of promoting qi and dispersing cold, relieving pain, and uses its volatility to guide the medicinal properties of various drugs into the blood and qi to reach the joint cavity and cartilage tissue of the affected area. Zanthoxylum bungeanum is warm in nature and pungent in taste, and belongs to the spleen, stomach, and kidney meridians. It warms the middle and relieves pain. It warms the interior to enter the spleen and kidney, disperses to reach the limbs, and leads the medicine directly to the lesion, removes dampness and numbness, and removes blood stasis and treats acid. In particular, Zanthoxylum bungeanum can greatly enhance the effect of Alpinia officinalis here. Although the dosage of both accounts for a small proportion in the prescription, due to the combined use, the human body absorption of curcumin in Alpinia officinalis is enhanced by 20 times, thereby reaching the prescription compatibility treatment dosage.

[0019] Further from the perspective of plant components, the single medicinal materials selected in the present invention all contain active ingredients that can inhibit uric acid production, promote uric acid excretion, protect the liver, kidney and spleen, and assist in the treatment of hyperuricemia.

[0020] Among them, chicory mainly contains chemical components such as polysaccharides, terpenes, flavonoids and phenolic acids. Its biological activities and pharmacological effects mainly include: antiviral effect; anti-inflammatory effect, which can improve ankle swelling, inflammation and lesions in rats, and is a potential drug for anti-gout; antioxidant effect, which plays a protective and antioxidant role in liver cell oxidative damage; immunomodulatory effect, which has the potential to treat autoimmune diseases; regulating sugar metabolism, increasing insulin release and sensitivity, improving glucose uptake, regulating enzyme activity, improving diabetes and its complications; liver and kidney organ protection. The components of chicory such as chlorogenic acid, aesculin, aesculin, scopoletin, polysaccharides, and chicoric acid are closely related to the treatment of hyperuricemia by chicory, and have good safety, which may be related to the inhibition of xanthine oxidase (XOD) and adenosine deaminase (ADA) activity. Chicory water extract can significantly reduce the uric acid concentration in mice with acute hyperuricemia (P<0.05). Under the same conditions, the 70% alcohol extract of chicory has a better uric acid-lowering effect than the water extract of chicory. Since the various biological activities of chicory can act synergistically on hyperuricemia, the present invention selects chicory as the first monarch drug.

[0021] Astragalus mainly contains flavonoids, polysaccharides, saponins, amino acids, trace elements, etc. Its pharmacological effects and therapeutic applications are mainly in improving immunity, protecting the brain and heart, lowering blood lipids, anti-tumor, lowering blood sugar, neuroprotection, anti-aging, anti-ulcer, and protecting the liver and kidneys. Further special research found that astragalus extract can significantly reduce the blood uric acid and XOD activity values ​​of hyperuricemia mice, improve the kidney damage of mice to a certain extent, and promote the protein expression of intestinal uric acid transporter ABCG2. Astragalus extract can also promote the excretion of uric acid by regulating uric acid transporters, and has a dual uric acid-lowering effect of inhibiting uric acid generation and promoting uric acid excretion, and the uric acid-lowering effect is significant, so the present invention uses it as the second monarch drug.

[0022] The study on the uric acid-lowering effect of the combined use of chicory and astragalus found that the effect of equal-amount combined use is better than the use of the two herbs alone, and has a dose-effect significance: the effect of equal-amount combined use is significantly better than the effect of using the two herbs alone, and there is also a great improvement in the effectiveness index.

[0023] Papaya mainly contains organic acids, triterpenes, saponins, sugars, tannins, flavonoids and peroxidase, and has anti-inflammatory, analgesic, liver-protecting, anti-tumor, anti-rheumatic, anti-aging and antibacterial effects. Modern pharmacological studies have shown that papaya ethanol extract has good effects of lowering enzymes, protecting the liver, and improving liver function, among which oleanolic acid and ursolic acid are the main active ingredients; papaya glycosides have anti-inflammatory and immunomodulatory functions and anti-rheumatic and rheumatoid effects. Papaya extracts contain papaya polysaccharides, papaya polyphenols, papaya flavonoids, and papaya organic acids, which have antioxidant, anti-fatigue, and lipid-lowering effects. Therefore, papaya as an auxiliary medicine has a definite and significant effect on liver protection, antioxidant, and anti-rheumatic.

[0024] Eucommia ulmoides mainly contains abundant active ingredients and relatively extensive pharmacological effects such as lignans, iridoids, flavonoids, phenylpropanoids, terpenes, polysaccharides, etc., and the present invention mainly selects its pharmacological effects of liver protection, kidney protection, anti-inflammatory, antioxidant and sedative relaxation, and selects a method that is conducive to the extraction of corresponding active ingredients such as lignans, iridoids, flavonoids, phenylpropanoids, etc., and enriches these active ingredients as much as possible at the crude extraction level to achieve the purpose of assisting the main drug.

[0025] Mango leaves mainly contain flavonoids, benzophenones, phenolic acids, lignans, triterpenes, volatile components, etc., and also contain inorganic elements and other chemical substances. Among them, flavonoids, benzophenones and phenolic acids are its main active ingredients. Mango leaves have pharmacological effects such as anti-inflammatory, antioxidant, anti-diabetic, anti-tumor, liver protection, analgesia, and hypolipidemic, and many of its pharmacological effects are mainly attributed to chemical substances such as mangiferin, phenolic acids, and benzophenones. The present invention focuses on the extraction and application of flavonoids such as mangiferin, while taking into account phenolic acids and benzophenones. In order to achieve the effects of liver protection, lung protection, anti-inflammatory, and anti-oxidation auxiliary medicine.

[0026] Daidaihua mainly contains flavonoids, alkaloids and volatile oils. Daidaihua is rich in flavonoid compounds, mainly including hesperidin, neohesperidin and limonene. Flavonoids have pharmacological activities such as antioxidant, antiviral, anti-inflammatory and liver protection. Daidaihua alkaloids have antioxidant, weight loss, lipid-lowering, anti-cancer and antiviral pharmacological activities. The volatile oil composition is complex, among which terpenes are the most common. Daidaihua volatile oil has sedative, anti-anxiety, anti-depressant and antibacterial effects. The present invention uses active ingredients with anti-inflammatory, antioxidant, liver protection and sedative effects as the target extract to achieve the purpose of assisting the main medicine to exert its efficacy.

[0027] Gastrodia elata has the effects of regulating lipid metabolism disorder, anti-oxidative damage, anti-inflammatory damage and protecting endothelial cell damage, anti-oxidative, anti-inflammatory, analgesic, improving cardiovascular and cerebrovascular diseases, and anti-diabetes, which is closely related to its rich functional ingredients such as phenols, flavonoids, polysaccharides, sterols, organic acids, terpenes, trace elements, volatile oils, etc. Among them, gastrodia elata phenols and their glycoside components such as gastrodin, p-hydroxybenzyl alcohol and barisin glycoside compounds are all its main sources of pharmacological activity. The present invention mainly uses the characteristics of regulating lipid metabolism disorder, anti-oxidative damage, anti-inflammatory damage and protecting endothelial cell damage of Gastrodia elata, and uses the active substances gastrodin and polyphenols with this effect as the key extraction targets.

[0028] Chinese yam mainly contains active substances such as dioscin, dopamine, allantoin, polyphenol oxidase, and yam hydrochloride, which have the pharmacological effects of protecting liver, anti-inflammatory, tonifying kidney and astringing essence, and lowering blood sugar. The liver-protecting effect of Chinese yam is related to the antioxidant activity of Chinese yam polysaccharides. In addition, Chinese yam saponin extract has a significant effect of reducing uric acid in mouse serum. The present invention focuses on the pharmacological effects of Chinese yam in anti-oxidation, protecting liver and tonifying kidney, and promoting uric acid excretion.

[0029] Corn silk mainly contains active ingredients such as flavonoids, saponins, polysaccharides sitosterol and stigmasterol, alkaloids, volatile oils, tartaric acid, etc. The active ingredients of corn silk can be antioxidant, anti-fatigue, lower blood lipids, and act as a diuretic, thereby increasing uric acid excretion.

[0030] The water extract and alcohol extract of Alpinia officinalis are rich in uric acid-lowering active ingredients. Further studies have shown that flavonoids such as galangin, kaempferol, quercetin, apigenin, and phenylpropanoids, volatile oils, glycosides, organic acids, and terpenoids all show significant activity in inhibiting uric acid conversion (inhibiting xanthine oxidase) or promoting uric acid excretion. Among them, the alcohol extract and total flavonoids of Alpinia officinalis can effectively reduce the uric acid value and urea nitrogen value in mouse serum; the water extract can reduce the creatinine value and urea nitrogen value; the polysaccharide group can also reduce the creatinine value. Although the dosage is relatively low in the present invention, because of the use of modern extraction technology, its content purity is relatively high, and because of the synergistic effect of pepper, the human body utilization is increased by more than 20 times, so it can assist the two main medicines to share the task of reducing blood uric acid.

[0031] Toona sinensis leaves are rich in terpenoids, flavonoids and flavonol glycosides, phenolic compounds, and phenylpropanoid compounds, which have physiological effects such as liver protection, antiviral, antibacterial, anti-inflammatory, and anti-tumor. The 70% ethanol extract of Toona sinensis leaves has a strong inhibitory effect on xanthine oxidase and cyclooxygenase-2, which is the key to gout and hyperuricemia; the total flavonoid extract of Toona sinensis leaves can significantly reduce the serum uric acid level of hyperuricemia mice (P < 0.001) and restore it to the level of normal mice (P > 0.5).

[0032] Emblica officinalis mainly contains polyphenols, tannins, flavonoids, polysaccharides and triterpenes, and has antioxidant, antibacterial, anti-inflammatory, anti-tumor, liver-protecting and uric acid-lowering pharmacological effects.

[0033] Coix seeds mainly contain starch, fatty acids and esters, polysaccharides, proteins, phenolic acids, sterols, flavonoids, lactams, triterpenes, alkaloids, adenosine, etc., which have analgesic and anti-inflammatory activities, regulate glucose and lipid metabolism, enhance immunity, lower blood pressure, anti-oxidation, and anti-aging activities. The total polyphenols in coix seeds include bound and free types, which have the functions of scavenging free radicals, anti-cancer, enhancing immunity, lowering blood pressure and blood sugar, and anti-inflammatory and analgesic functions. Bound polyphenols are more related to intestinal health, usually released after fermentation by bacteria in the colon, and play a role in uric acid excreted through the intestines.

[0034] Poria cocos mainly contains triterpenes, polysaccharides, sterols, volatile oils, proteins, amino acids and trace elements, among which triterpenes and polysaccharides are the main active ingredients of Poria cocos. Polysaccharides account for about 70% to 90% of the dry weight of its sclerotium, and have important functions such as anti-tumor, anti-inflammatory and immunomodulatory. Poria cocosin is a multi-component tetracyclic triterpenoid compound that can bind to the aldosterone receptors on the rat renal plasma membrane in vitro, antagonize aldosterone activity in vivo, and inhibit the renal tubular response to Na + reabsorption and K +The excretion of urine is beneficial; the ethanol extract of Poria peel has a significant diuretic effect; Pachycolic acid relieves intestinal microcirculation disorders, prevents platelet aggregation, and avoids microthrombosis, thereby achieving the effect of treating edema. The present invention utilizes the biological activity of Poria polysaccharide and triterpenoid compounds to promote diuresis and detumescence, regulate immunity, resist oxidation, lower blood sugar, resist inflammation and relieve pain, and regulate the nervous system, thereby assisting the main drug in exerting its efficacy.

[0035] Kaempferol mainly contains volatile oil, kaempferol, kaempferol, protein, starch, and mucus, and has strong antioxidant pharmacological effects. Kaempferol active substances can inhibit inflammatory responses through various pathways. The flavonoid compound kaempferol has antibacterial, anti-inflammatory, antioxidant and anti-tumor pharmacological effects, and can also significantly reduce the content of uric acid in the serum of hyperuricemia mice.

[0036] Zanthoxylum bungeanum is rich in volatile oil, alkaloid, flavonoid, phenylpropanoid and other compounds, and has anti-inflammatory, analgesic, local anesthesia, anti-tumor, anti-oxidation, cardiovascular protection, bactericidal and antipruritic pharmacological activities. Among them, amide substances are represented by sanshool, which has significant analgesic, anti-inflammatory and local anesthesia, liver protection, anti-ulcer and anti-diarrhea pharmacological properties. The application focus of the present invention to Zanthoxylum bungeanum is sanshool.

[0037] The pharmaceutical composition of the present invention comprises the extract of the anti-hyperuricemia Chinese medicine composition of the present invention and a pharmaceutically acceptable carrier.

[0038] Preferably, the pharmaceutical composition of the present invention is in the form of granules, tablets, capsules, pastes, and oral solutions.

[0039] The method for preparing the extract of the Chinese medicine composition of the present invention is selected from any of the following methods:

[0040] Method 1:

[0041] Add 1.5 to 3 times the total weight of the medicinal materials in water, soak, extract, and obtain a first extract; add the remaining medicinal residues in water equal to the first extraction, soak, extract, and obtain a second extract; add the remaining medicinal residues in water half the first extraction, soak, and obtain a third extract; combine the three extracts to obtain the extract of the traditional Chinese medicine composition;

[0042] Method 2:

[0043] Prepare the extract of each medicinal material, concentrate, and dry to obtain the extract of each medicinal material; or add a pharmaceutically acceptable carrier after concentration to obtain the extract of each medicinal material; mix the extracts of each medicinal material to obtain the extract of the traditional Chinese medicine composition.

[0044] Preferably, in method 2, each of the obtained extracts is concentrated to an extract having a relative density of 1.30 to 1.40.

[0045] Preferably, in method 2, dry powder of Chinese herbal extract is prepared: according to different medicinal materials, 8% to 15% dextrin is added to calibrate the required proportion, and each medicinal material concentrate and extract is respectively made into 80-120 mesh powder with a moisture content of less than 7% by spray drying.

[0046] Specifically, each Chinese herbal medicine extract is pumped into a concentration pot according to the calculated weight, vacuum concentrated into an extract with a predetermined thermal density, the concentrate is filtered while hot, and then pumped into the concentrate for batching. The concentration of the feed liquid required for spray drying is further calibrated, and a certain proportion of dextrin, micro-powder silica gel, sodium stearyl fumarate, etc. (to improve the viscosity of the medicinal material extract and the fluidity of the powder) is added, and spray dried into powder.

[0047] The specific preparation methods of the extracts and extract powders in method 2 are as follows:

[0048] 1. Water extraction

[0049] With water as the extraction solvent, after the medicinal material slices are crushed, water is added at a solid-liquid ratio of 1:13 (g / mL), heated under reflux for leaching, and the solid-liquid separation is performed to obtain an extract, which is concentrated to a temperature of 80°C and a specific gravity of 1.35. After solid-liquid separation, the amount of dextrin is calculated according to the ratio of the extract to the medicinal material of 1:30, and 1% of the total amount of dry extract powder and 0.5% of sodium stearyl fumarate are added at the same time, and spray drying is performed to obtain the extract powder.

[0050] 2. Ethanol extraction

[0051] Using ethanol of different concentrations as the extraction solvent, the Chinese herbal medicine pieces are crushed and extracted 2-3 times, the solid-liquid ratio (g / mL) is 1:(5-13), the ethanol concentration (volume fraction) is 50%-85% for three times, heating reflux extraction, solid-liquid separation after each extraction, and the extract is combined. Concentrate to 50-60°C with a relative density of 1.3-1.4, separate the solid and liquid, calculate the corresponding amount of dextrin according to the extract ratio of 30:1, add 1% micro powder silica gel and 0.5% sodium stearyl fumarate to the total amount of dry extract, spray dry, and obtain the extract powder.

[0052] 3. Ethanol / water or water / ethanol extraction

[0053] The Chinese herbal medicine slices are crushed, firstly alcohol extracted, ethanol is added at a solid-liquid ratio (g / mL) of 1: (8-15), the ethanol concentration (volume fraction) is 70%-80%, soaked under stirring, extracted at 50-70°C under stirring, the extract is cooled, and the solid-liquid is separated. Water extraction is performed at a solid-liquid ratio (g / min) of 1: (8-20), water is added, soaked under stirring, extracted at 70-80°C under stirring, the extract is cooled, and the solid-liquid is separated. The alcohol extract is pumped into a concentration pot, heated under vacuum to recover ethanol, and when the sample is smelled without alcohol, the water extract is added, concentrated to a relative density of 1.3-1.4 at 60-70°C, and the corresponding amount of dextrin is calculated according to the ratio of extract content of 10:1-30:1 (mass ratio of herbal medicine slices to extract powder), and 1% micro powder silica gel and 0.5% sodium stearyl fumarate are added to the total amount of dry extract, spray dried, and the extract powder is obtained.

[0054] Or the Chinese herbal medicine slices are crushed, firstly extracted with water according to the material-liquid ratio of 1:(10-20), soaked, refluxed and extracted, and separated the solid and liquid. The material-liquid ratio of alcohol extraction is 1:(12-15) (g / mL), 50%-70% ethanol is extracted at 50-70°C, and the solid and liquid are separated. The alcohol extract recovers ethanol, mixes with the water extract, and concentrates to a temperature of 60-65°C with a relative density of 1.3-1.4, separates the solid and liquid, and calculates the corresponding amount of dextrin according to the extract content of 30:1, and adds 1% micro powder silica gel and 0.5% sodium stearyl fumarate to the total amount of dry extract, spray-drying, and the extract powder is obtained.

[0055] 4. Ultrasonic assisted ethanol extraction

[0056] The Chinese herbal medicine slices are crushed, and ethanol is added according to a solid-liquid ratio of 1: (15-25), and the ethanol concentration (volume fraction) is 60%-80%, and the mixture is stirred and soaked. Ultrasonic extraction is performed at room temperature to 70°C, and the extract is cooled and solid-liquid separation is performed. The extract is concentrated to a temperature of 50-70°C and a relative density of 1.3-1.4. After solid-liquid separation, a corresponding amount of dextrin is added according to the extract ratio content of 30:1, and 1% micro-powder silica gel and 0.5% sodium stearyl fumarate are added to the total amount of dry extract, and spray drying is performed to obtain extract powder.

[0057] 5. Water extraction and alcohol precipitation / water extraction and alcohol dissolution

[0058] The Chinese herbal medicine pieces are crushed into 60-80 mesh coarse powder, and water is added at a solid-liquid ratio of 1: (6-15). The extract is stirred at 80-90°C, and the extract is cooled, the solid-liquid separation is performed, and the supernatant is collected. The extract is concentrated to an extract with a relative density of 1.35-1.40 at 60-65°C. The extract is cooled and precipitated with alcohol, and the solid-liquid separation is performed, and the supernatant is collected. The water-extracted alcohol-precipitated solid and the water-extracted alcohol-soluble extract are obtained respectively.

[0059] The obtained water-extracted alcohol-soluble extract is subjected to vacuum to recover ethanol, and concentrated into an extract having a specific gravity of 1.35-1.40 at 65°C, and mixed with the alcohol-precipitated solids, and the total amount of dry extract is converted according to the mass ratio of the extract to the amount of Chinese herbal medicine pieces of 1:10 (minus the water difference between the extract and the extract). 7-10% of β-dextrin and 3-5% of micro-powdered silica gel are added to the total amount of dry extract under stirring at room temperature, stirred evenly, dried with hot air at 80°C, crushed and sieved, and the middle sieve of 80 mesh to 120 mesh is taken to obtain the water-extracted alcohol-precipitated extract powder.

[0060] 6. Microwave intermittent assisted ethanol extraction

[0061] The Chinese herbal medicine slices are crushed into 40 mesh coarse powder, and 70% (volume fraction) ethanol is added according to a material-liquid ratio of 1:25, and the microwave power is 600W. The microwave irradiation is turned on for 1 minute every 4 minutes, and the switch is turned on and off 4 times, and the total extraction time is 20 minutes; vacuum filtration is performed for solid-liquid separation, and the extract is put into a concentration pot, and the ethanol is recovered under vacuum, and the concentration is concentrated to a specific gravity of 1.30-1.40 at a temperature of 50°C, and the solid-liquid separation is performed. The total amount of dry extract is converted according to the mass ratio of the extract to the Chinese herbal medicine slice feed amount of 1:30 (minus the water difference between the extract and the extract). 1% micro-powder silica gel and 0.5% sodium stearyl fumarate are added to the total amount of dry extract, and pure water is calibrated to a specific gravity of 1.20, and a spray drying tower is used to spray dry the extract powder under the conditions of an inlet temperature of 122°C, an outlet temperature of 110°C, a feed liquid temperature of 85°C, and a nozzle pressure of 0.4MPa.

[0062] Preferably, when the pharmaceutical composition of the present invention is an oral solution, each concentrated solution in method 2 is weighed according to the prescription ratio to prepare a solution, and pharmaceutically acceptable excipients for oral solution are added and quantitatively filled to obtain the solution.

[0063] Preferably, the mass ratios of the decoction pieces of chicory leaves, astragalus, papaya, mango leaves, eucommia, daidaihua, galangal, gastrodia, toona sinensis leaves, emblica, coix seeds, yam, corn silk, poria, galangal and zanthoxylum bungeanum to the extract in the second method are 30:1, 30:1, 30:1, 30:1, 30:1, 30:1, 30:1, 30:1, 30:1, 30:1, 20:1, 10:1, 30:1, 10:1, 30:1, 30:1, 30:1, 30:1, respectively.

[0064] Preferably, the mixing mass ratio of the medicinal material extracts of chicory leaves, astragalus, papaya, mango leaves, eucommia, daidai hua, galangal, gastrodia, toona sinensis leaves, emblica, coix seeds, yam, corn silk, poria, galangal and zanthoxylum bungeanum in method 2 is (15-30):(15-30):(6-10):(6-10):(3-7):(3-7):(3-7):(3-7):(3-7):(3-7):(3-7):(3-7):(3-7):(3-7):(3-7):(3-7):(2-4):(2-4):(2-3).

[0065] Further preferably, the mixing mass ratio of the medicinal material extracts of chicory leaves, astragalus, papaya, mango leaves, eucommia, daidaihua, galangal, gastrodia, toona sinensis leaves, emblica, coix seeds, yam, corn silk, poria, kaempferia galanga, and zanthoxylum bungeanum in method 2 is 20:20:8:8:4:4:4:4:4:4:4:4:4:4:3:3:2.

[0066] The anti-hyperuricemia Chinese medicine composition and the pharmaceutical composition thereof of the present invention are used in the preparation of drugs for reducing uric acid.

[0067] Preferably, the drug is a drug that inhibits uric acid reabsorption and promotes uric acid excretion, which is specifically manifested in the ability to reduce the levels of uric acid, creatinine, and urea nitrogen in serum and urine, down-regulate the expression levels of renal uric acid transporter URAT1 and glucose transporter GLUT9, and up-regulate the expression levels of uric acid secretion proteins OAT1 and OAT3.

[0068] Beneficial effects: Compared with the prior art, the present invention has the following significant advantages:

[0069] The Chinese medicine composition designed by the present invention adopts medicinal materials with the same origin as medicine and food, treats the disease from the perspective of the liver, adopts the treatment methods of soothing the liver and strengthening the spleen and tonifying the liver and kidney, achieves the effect of reducing uric acid by inhibiting uric acid reabsorption and promoting uric acid excretion, and has a definite therapeutic effect on hyperuricemia. The medicinal material source is stable, and the dosage of the medicine is reduced through synergistic effects between the medicinal materials. The medicine is safe and effective, and the clinical application is flexible, and it can be prepared into different dosage forms according to needs. The preparation process is stable and controllable, and it is easy to scale up. BRIEF DESCRIPTION OF THE DRAWINGS

[0070] Figure 1 The results are as follows: The effect of the Chinese medicine composition on the levels of serum uric acid (SUA) and urine uric acid (UUA) in hyperuricemia mice (mean ± standard deviation, compared with the model group: **P<0.01, *P<0.05);

[0071] Figure 2 The results are as follows: The effect of the Chinese medicine composition on the serum creatinine (SCR) and urine creatinine (UCR) levels of hyperuricemia mice (mean ± standard deviation, compared with the model group: **P<0.01, *P<0.05);

[0072] Figure 3 The results show the effect of the Chinese medicine composition on the levels of serum urea nitrogen (SBUN) and urine urea nitrogen (UBUN) in hyperuricemia mice (mean ± standard deviation, compared with the model group: **P<0.01, *P<0.05);

[0073] Figure 4The results are as follows: The effect of the Chinese medicine combination on the gene expression level of uric acid transporter URAT1 in the kidneys of hyperuricemia mice (mean ± standard deviation, compared with the model group: **P<0.01);

[0074] Figure 5 The results are as follows: the effect of the Chinese medicine composition on the gene expression level of glucose transporter GLUT9 in the kidney of hyperuricemia mice (mean ± standard deviation, compared with the model group: **P<0.01, *P<0.05);

[0075] Figure 6 The results are as follows: The effect of the Chinese medicine combination on the gene expression level of uric acid secretion protein OAT1 in the kidneys of hyperuricemia mice (mean ± standard deviation, compared with the model group: **P<0.01, *P<0.05);

[0076] Figure 7 The results are as follows: The effect of the Chinese medicine combination on the gene expression level of uric acid secretion protein OAT3 in the kidneys of hyperuricemia mice (mean ± standard deviation, compared with the model group: **P<0.01, *P<0.05);

[0077] Figure 8 These are the results of the effect of the Chinese medicine composition on the expression level of uric acid-related transporter proteins in the kidneys of hyperuricemia mice. DETAILED DESCRIPTION

[0078] The technical solution of the present invention is further described below in conjunction with embodiments.

[0079] Example 1: Preparation and application of Chinese medicine decoction

[0080] 1. Ratio and weighing of Chinese herbal medicines

[0081] Calculated by weight, the proportions of the Chinese herbal medicines are: 20 parts of chicory leaves, 20 parts of astragalus, 8 parts of papaya, 8 parts of mango leaves, 4 parts of eucommia, 4 parts of daidai hua, 4 parts of galangal, 4 parts of gastrodia, 4 parts of toona sinensis leaves, 4 parts of emblica, 4 parts of coix seeds, 4 parts of yam, 4 parts of corn silk, 3 parts of poria, 3 parts of galangal and 2 parts of Zanthoxylum bungeanum.

[0082] Based on the weight of 300g per dose, convert the weight of each portion to 3g, accurately weigh each Chinese herbal medicine slice and put it into a non-iron container.

[0083] 2. Preparation and application of Chinese herbal medicine decoction

[0084] Adopt the three-decoction method, add drinking water (about 900ml) 3 times the weight of the medicinal materials for the first time, soak for 120 minutes, boil over high heat, simmer over low heat for 60 minutes, pour out the first decoction (about 300ml); continue to add drinking water of the same weight as the first time (about 900ml) into the medicine pot, soak for 60 minutes, boil over high heat, simmer over low heat for 40 minutes, pour out the second decoction (about 400ml); continue to add drinking water (about 450ml) 1.5 times the weight of the original medicinal materials into the medicine pot, soak for 30 minutes, boil over high heat, simmer over low heat for 20 minutes, pour out the third decoction (about 200ml), combine the three decoctions, and store at low temperature.

[0085] Take three times a day, 300 ml each time. One course of treatment is 30 days. Take 3-5 courses of treatment depending on the condition. During the medication period, test blood uric acid once every two weeks. Depending on the rate of decrease of blood uric acid value, increase or decrease the dosage as appropriate. It can also be used as a long-term treatment and health care medicine for patients with hyperuricemia, and the dosage is reduced to 2 times a day or once a day, two doses in three days or one dose every two days.

[0086] Example 2: Preparation of extracts of Chinese herbal medicines

[0087] (1) Chicory: The target extraction components are flavonoids, phenylpropanoids, phenolic acids and other compounds such as chicoric acid, chlorogenic acid, scopolamine, scopolamine, etc., using two ultrasonic-assisted alcohol extractions and one ultrasonic-assisted water extraction.

[0088] Specific operation method: a. Alcohol extraction: the slices are crushed into 80 meshes, and 70% (volume fraction) ethanol is added according to the material-liquid ratio of 1:12 (medicinal slices: extraction solvent, mass volume ratio, the same below), the ultrasonic power is 300w, the extraction temperature is 50℃, the extraction time is 45min, the second extraction method is the same as the first, solid-liquid separation, and the two alcohol extracts are combined; b. Water extraction: the solid residue after alcohol extraction is dried, and pure water is added according to the material-liquid ratio of 1:8, the extraction temperature is 80℃, the ultrasonic power is 300w, the solid-liquid separation is carried out, and the extract powder is cooled to room temperature. c. Mix the two extracts, and calculate the corresponding amount of dextrin (about 10% to 15%) according to the extract content of 30:1 (the mass ratio of medicinal slices to extract powder, the same below), and add 1% micro-powder silica gel and 0.5% sodium stearyl fumarate to the total amount of dry extract, and adjust the feed liquid with a specific gravity of 1.20 with pure water at room temperature, spray dry, and obtain the extract powder.

[0089] (2) Astragalus: The target components for extraction are flavonoids, phenylpropanoids, phenolic acids, alkaloids, terpenes, etc., using secondary alcohol extraction and primary water extraction.

[0090] Specific operation method: a. Cut the slices of Astragalus membranaceus into 2mm pieces, first add 75% (volume fraction) ethanol at a solid-liquid ratio of 1:12 (g / mL), extract at 70℃, extract twice, separate the solid and liquid, and combine the two extracts. b. Add pure water to the residue at a solid-liquid ratio of 1:10 (g / mL), extract at 100℃, and separate the solid and liquid. Combine the two extracts and concentrate to a relative density of 1.3 to 1.35 at 60℃. c. Solid-liquid separation, add the corresponding amount of dextrin according to the 30:1 ratio of the extract, and add 1% micro-powder silica gel and 0.5% sodium stearyl fumarate to the total amount of dry extract, adjust the feed liquid with a specific gravity of 1.20 with pure water at room temperature, spray dry, and obtain the extract powder.

[0091] (3) Papaya: The target components for extraction are flavonoids, phenolic acids, alkaloids, polysaccharides, triterpenes and their glycosides, such as oleanolic acid and ursolic acid, using one water extraction and two alcohol extractions.

[0092] Specific operation method: a. Water extraction: Papaya slices are crushed into coarse particles below 2mm, water is added according to the material-liquid ratio of 1:20, soaked for 120min, ultrasonic power 450w treatment for 10min, and reflux extraction at 88℃ for 90min. Collect the extract while hot for solid-liquid separation. b. Alcohol extraction: material-liquid ratio 1:12 (g / mL), ultrasonic power 450w treatment for 5min, 50%~60% concentration of ethanol at 70℃ for 95min, solid-liquid separation, the second alcohol extraction method is the same as the first. Combine the two alcohol extracts and recover ethanol. c. The three extracts are mixed and concentrated to a temperature of 60℃ with a relative density of 1.3~1.4. According to the extract ratio of 30:1, the corresponding amount of dextrin is calculated, and 1% micro-powder silica gel and 0.5% sodium stearyl fumarate are added to the total amount of dry extract. At room temperature, pure water is used to adjust the feed liquid with a specific gravity of 1.20, and spray drying is performed to obtain the extract powder.

[0093] (4) Mango leaves: Mangiferin, phenolic acids and xylene ketone active substances were extracted by ethanol heating reflux.

[0094] Specific operation method: a. Crush the mango leaf slices, add 70% (volume fraction) ethanol and soak for 60 minutes according to the solid-liquid ratio of 1:10, heat to 100℃, reflux extraction for 120 minutes, and extract 3 times. Solid-liquid separation, combine the three extracts, recover ethanol, and concentrate to a temperature of 60℃ with a relative density of 1.35-1.40. b. According to the 30:1 ratio of the extract, calculate the corresponding amount of dextrin, add 1% micro-powder silica gel and 0.5% sodium stearyl fumarate to the total amount of dry extract, adjust the liquid with a specific gravity of 1.20 with pure water at room temperature, spray dry, and obtain the extract powder.

[0095] (5) Eucommia ulmoides: Eucommia ulmoides flavonoids, phenylpropanoids, terpenoids and other compounds were extracted by ethanol heating and reflux.

[0096] Specific operation method: a. Crush Eucommia ulmoides slices into 20 meshes, add 75% (volume fraction) ethanol and soak for 60 minutes according to the material-liquid ratio of 1:13, heat to 100℃, reflux extraction for 120 minutes, solid-liquid separation, the second extraction method is the same as the first. b. Combine the two extracts, recover ethanol, and concentrate to a relative density of 1.3-1.4 at 50℃. c. According to the 30:1 ratio of the extract, calculate the corresponding amount of dextrin, add 1% micro-powder silica gel and 0.5% sodium stearyl fumarate to the total amount of dry extract, adjust to a liquid with a specific gravity of 1.20 with pure water at room temperature, spray dry, and obtain the extract powder.

[0097] (6) Herba Lysimachiae: The target components for extraction are flavonoids, alkaloids, and volatile oils from Herba Lysimachiae, and ultrasound-assisted ethanol extraction is used.

[0098] Specific operation method: a. Break the Daidaihua slices into pieces, add 52% (volume fraction) ethanol according to the material-liquid ratio of 1:5, ultrasonic power 400w, extraction temperature 73℃, extraction time 52min, and repeat the extraction once. Solid-liquid separation, combine the two alcohol extracts, recover ethanol, and concentrate to a temperature of 50℃ with a relative density of 1.3-1.35. b. Add the corresponding amount of dextrin according to the 30:1 ratio content of the extract, and add 1% micro-powder silica gel and 0.5% sodium stearyl fumarate to the total amount of the concentrate, adjust the feed liquid with a specific gravity of 1.20 with pure water at room temperature, spray dry, and obtain the extract powder.

[0099] (7) Alpinia officinalis: Flavonoid compounds such as galangin were selected as the target components and extracted by ethanol heating and reflux.

[0100] Specific operation method: Slightly crush the galangal slices, add 85% (volume fraction) ethanol to soak for 60 minutes according to the material-liquid ratio of 1:8, heat to 100℃, reflux extraction for 120 minutes, solid-liquid separation, and repeat the extraction twice. Combine the three extracts and concentrate to a relative density of 1.3-1.4 at 50℃. b. Add the corresponding amount of dextrin according to the 30:1 ratio of the extract, and add 1% micro-powder silica gel and 0.5% sodium stearyl fumarate to the total amount of the concentrate, adjust the liquid to a specific gravity of 1.20 with pure water at room temperature, spray dry, and obtain the extract powder.

[0101] (8) Gastrodia elata: Gastrodia elata and other target components are extracted by water heating reflux.

[0102] Specific operation method: a. Grind the Gastrodia elata slices, add deionized water with a pH of 5.5 according to a solid-liquid ratio of 1:13 (g / mL), heat to 100°C, reflux extraction for 220 minutes, separate the solid and liquid to obtain the extract, and concentrate to a temperature of 80°C with a specific gravity of 1.35-1.40. b. Solid-liquid separation, calculate the amount of dextrin added according to the ratio of extract to medicinal material of 1:30, and add 1% micro-silica gel and 0.5% sodium stearyl fumarate of the total amount of the extract at the same time, adjust the feed liquid with a specific gravity of 1.20 with pure water at room temperature, spray dry, and obtain the extract powder.

[0103] (9) Toona sinensis leaves: Flavonoids and phenylpropanoid compounds were selected as the extraction components, and microwave intermittent ethanol extraction was used.

[0104] Specific operation method: Toona sinensis leaf slices are crushed into 40 mesh coarse powder, with a solid-liquid ratio of 1:25, and 70% (volume fraction) ethanol is added. The microwave power is 600W, and the microwave irradiation is turned on for 1 minute every 4 minutes. The switch is on and off 4 times, and the total extraction time is 20 minutes; vacuum filtration is used for solid-liquid separation, and ethanol is recovered. Vacuum concentration is performed at a concentration temperature of 50°C to a relative density of 1.30-1.40. The particulate suspended matter in the extract is separated by a high-speed tubular centrifuge, and the clear extract is put into a batching tank. The corresponding amount of dextrin is added according to the 30:1 ratio content of the extract, and 1% micro-powder silica gel and 0.5% sodium stearyl fumarate are added to the total amount of the dry extract. The liquid is calibrated to a relative density of 1.20 with pure water at room temperature, and the extract powder is spray-dried in a spray drying tower at an inlet temperature of 122°C, an outlet temperature of 110°C, a liquid temperature of 85°C, and a nozzle pressure of 0.4MPa.

[0105] (10) Phyllanthus emblica: The target components for extraction were flavonoids such as rutin, quercetin, myricetin and their glycosides, and some phenolic acids and terpenes, using ultrasonic-assisted ethanol extraction.

[0106] Specific method: a. Crush the emblica slices, add 60% (volume fraction) ethanol according to the liquid-to-solid ratio of 25:1 mL / g, 60°C, ultrasonic power of 300w, extraction time of 20min, solid-liquid separation, concentrate to 60°C relative density of 1.35-1.40. b. Solid-liquid separation, add the corresponding amount of dextrin according to the 30:1 ratio content of the extract, and add 1% micro-powder silica gel and 0.5% sodium stearyl fumarate to the total amount of the concentrate, calibrate with pure water at room temperature to a relative density of 1.20, spray dry, and obtain the extract powder.

[0107] (11) Coix seed: Polyphenols, alkaloids and polysaccharides are targeted as components, and secondary alcohol extraction is used, followed by secondary water extraction and alcohol precipitation.

[0108] Specific method: a. Alcohol extraction: crush coix seed, add it to the extraction tank, add 70% ethanol by volume at a solid-liquid ratio of 1:10 (g / mL), and stir and extract at 60°C. Solid-liquid separation, collect the filtrate. The filter residue is extracted again according to the above steps, and after combining the two filtrates, the ethanol is recovered and concentrated to a specific gravity of 1.3-1.4 at 60°C. b. Water extraction: add water to the filter residue after alcohol extraction at the same solid-liquid ratio, extract twice according to the above extraction conditions, combine the filtrates and concentrate under reduced pressure to a specific gravity of 1.3-1.4 at 60°C to obtain a water extract. The water extract extract is precipitated with alcohol, the solid-liquid separation is carried out, the precipitate is dried to obtain the coix seed water extract alcohol precipitate, and the supernatant is concentrated to obtain the coix seed water extract alcohol soluble. c. Combine the three extracts, add the corresponding amount of dextrin according to the 20:1 ratio of the extract content, and add 1% micro-powder silica gel and 0.5% sodium stearyl fumarate to the total amount of the extract, calibrate with pure water to a relative density of 1.20 at room temperature, spray dry, and obtain the extract powder.

[0109] (12) Chinese Yam: The total flavonoids and polysaccharides of Chinese Yam were extracted by ultrasonic-assisted heating with alcohol followed by water.

[0110] Specific operation method: a. Ultrasonic alcohol extraction: crush the yam, add 75% ethanol by volume at a solid-liquid ratio of 1:15, and perform ultrasonic extraction at 70°C, separate the solid and liquid, and concentrate to a specific gravity of 1.3 at 70°C. After solid-liquid separation, obtain the yam alcohol extract. b. Ultrasonic water extraction: add water to the filter residue after alcohol extraction at a solid-liquid ratio of 1:20, perform ultrasonic extraction at 81°C, separate the solid and liquid to obtain the extract, and concentrate to a specific gravity of 1.35-1.40 at 75°C. Alcohol precipitation, concentrate the supernatant to a specific gravity of 1.35 at 70°C, and obtain the water-extracted alcohol-precipitated alcohol-soluble product. The precipitate is dried to obtain yam polysaccharide. c. Mix the alcohol extract, water-extracted alcohol-precipitated solids and alcohol-soluble extract, add the corresponding amount of dextrin according to the extract content of 10:1, and add 1% micro-powder silica gel and 0.5% sodium stearyl fumarate to the total amount of dry extract, calibrate with pure water at room temperature to a relative density of 1.20, spray dry, and obtain the extract powder.

[0111] (13) Corn silk: Total flavonoids, saponins, and alkaloid compounds were selected as the extraction target components, and ultrasonic-assisted alcohol extraction was used.

[0112] Specific operation method: a. Crush corn silk slices, add 60% ethanol by volume at a solid-liquid ratio of 1:20, 60℃, ultrasonic power 300w, extract for 120min, solid-liquid separation, repeat extraction once, combine two extracts, recover ethanol, concentrate at 60℃ with a relative density of 1.35-1.40. b. Add the corresponding amount of dextrin according to the extract content of 30:1, and add 1% micro-powder silica gel and 0.5% sodium stearyl fumarate to the total amount of dry extract, calibrate with pure water at room temperature to a relative density of 1.20, spray dry, and obtain extract powder.

[0113] (14) Poria cocos: Triterpenes and polysaccharides were selected as the target components for extraction, and heating reflux alcohol extraction and ultrasound-assisted water extraction were used.

[0114] Specific operation method: a. Slice the Poria cocos slices, add 70% ethanol by volume according to the material-liquid ratio of 1:8, heat and reflux to extract twice, separate the solid and liquid, combine the two extracts, recover the ethanol, concentrate to 60℃ with a specific gravity of 1.35-1.40, separate the solid and liquid, and obtain the alcohol-extracted clear extract. b. Crush the alcohol-extracted filter residue, perform ultrasonic-assisted water extraction again, add water at a material-liquid ratio of 1:20, ultrasonic power of 500w, extraction time of 100min, separate the solid and liquid, concentrate to 60℃ with a specific gravity of 1.30, and obtain the water-extracted clear extract. c. Combine the alcohol-extracted extract and the water-extracted extract, add the corresponding amount of dextrin according to the extract content of 10:1, and add 1% micro-powder silica gel and 0.5% sodium stearyl fumarate to the total amount of the extract, calibrate with pure water at room temperature to a relative density of 1.20, spray dry, and obtain the extract powder.

[0115] (15) Kaempferia galanga: Active substances such as ethyl p-methoxycinnamate, kaempferol, and quercetin were selected as the extraction target components, and ultrasound-assisted ethanol extraction was used.

[0116] Specific operation method: a. Sieve the Kaempferia galanga slices, add 80% ethanol by volume at a solid-liquid ratio of 1:20, soak for 120 minutes, ultrasonic power 650w at room temperature, auxiliary extraction for 220 minutes, solid-liquid separation, repeat extraction of the residue twice, combine the filtrate, concentrate to 60℃ with a specific gravity of 1.3, and obtain the Kaempferia galanga alcohol extract. b. Add the corresponding amount of dextrin according to the extract ratio of 30:1, and add 1% micro-powder silica gel and 0.5% sodium stearyl fumarate to the total amount of dry extract, calibrate with pure water at room temperature to a relative density of 1.20, spray dry, and obtain the extract powder.

[0117] (16) Zanthoxylum bungeanum: The target components were extracted from Zanthoxylum bungeanum alkaloids, amides, phenylpropanoids, flavonoids, lignin and other compounds by ultrasonic-assisted heating reflux ethanol extraction.

[0118] Specific operation method: a. Crush the peel of Zanthoxylum bungeanum, add 70% ethanol by volume to soak according to the solid-liquid ratio of 1:16, ultrasonic power of 450w, heat reflux extraction, solid-liquid separation, and repeat the extraction twice under the same conditions of the filter residue. Combine the three extracts, concentrate to a specific gravity of 1.35 at 70°C, and separate the solid and liquid to obtain an alcohol-extracted clear extract. b. Add the corresponding amount of dextrin according to the 30:1 ratio of the extract, and add 1% micro-powder silica gel and 0.5% sodium stearyl fumarate to the total amount of the concentrate, calibrate with pure water at room temperature to a relative density of 1.20, spray dry, and obtain the extract powder.

[0119] Example 3: Preparation and application of uric acid-lowering granules

[0120] 1. Preparation of medicinal material extract powder mixture

[0121] The medicinal material extract powder composition is calculated based on 100kg, and the ingredients list is: 20kg of chicory leaf extract powder, 20kg of astragalus extract powder, 8kg of papaya extract powder, 8kg of mango leaf extract powder, 4kg of eucommia extract powder, 4kg of daikon taro extract powder, 4kg of galangal extract powder, 4kg of gastrodia elata extract powder, 4kg of toona sinensis leaf extract powder, 4kg of emblica extract powder, 4kg of coix seed extract powder, 4kg of yam extract powder, 4kg of corn silk extract powder, 3kg of poria extract powder, 3kg of kaempferia galanga extract powder, and 2kg of Zanthoxylum bungeanum extract powder.

[0122] Ingredients: Accurately weigh various types of Chinese herbal extracts according to the above ingredient list and pour them into the ingredient tank.

[0123] Mixing: Open the batching tank and stir for 10 minutes, open the cage and send it into the mixer to mix for 20 minutes.

[0124] 2. Preparation of uric acid-lowering granules

[0125] The powder mixture of each medicinal material extract obtained in the above steps is prepared according to the above-designed formulation ratio, and a pharmaceutically acceptable carrier is added, and wet granulation is performed to prepare granules. The specific method is as follows:

[0126] Preparation of wetting agent: Through experiments, the Chinese herbal extract used in the present invention already contains about 10% of the binder, so it is only necessary to use the wetting agent and add an appropriate amount of cosolvent. Therefore, the feed liquid tank is vacuum-absorbed 0.3% sodium carboxymethyl cellulose, 0.7% Tween 80, and 14% medical ethanol (70% volume fraction) by weight of each material extract powder mixture, stirred to fully dissolve and set aside.

[0127] Wet granulation: Suck the mixed raw materials into the granulation bin, turn on the main stirring, increase the speed to 600rpm, continue to mix for 2 minutes, turn on the liquid pump, raise the pressure to 0.4MPa, open the nozzle, control the spray speed to spray at 1BV, and start granulation. After 5 minutes, turn off the nozzle, turn off the liquid pump, reduce the main stirring speed of the granulation bin, and the granulation is completed, and wet granules of 60-80 mesh are obtained. Open the granulation bin, clean it for 3 minutes, and prepare for the next granulation.

[0128] Boiling drying: send the wet particles into the boiling drying chamber, close the door, turn on the induced draft fan to make the wet particles slightly boil in the chamber, open the steam heating chamber valve, send dry hot air into the boiling drying chamber, control the air inlet temperature at 110℃, the upper air outlet temperature at 80℃, boil and dry for 18 minutes, and after drying, send the dried particles to the laboratory to measure the moisture content. It is qualified if it does not exceed 7%. If it exceeds the standard, the drying time will be extended.

[0129] The qualified granules are packaged by DCF-300-B automatic packaging machine, with 10g strip back seals per bag, and packed into outer packaging boxes to obtain the finished products.

[0130] Example 4: Preparation of uric acid-lowering chewable tablets

[0131] 1. Preparation of medicinal material extract powder mixture

[0132] Same as Example 3.

[0133] 2. Preparation of uric acid-lowering chewable tablets

[0134] Ingredients: The medicinal material extract powder is prepared according to the formula of Example 3. Based on the total weight of the chewable tablets, the formulation is a mixture of medicinal material extract powder: 60%, magnesium stearate: 1.3%, microcrystalline cellulose: 12.7%, xylitol: 1%, and lactose: 25%. Accurately weigh and pour into the ingredient tank.

[0135] Mixing: Open the batching tank and stir for 10 minutes, then open the cage and send it into the mixer for mixing for 30 minutes.

[0136] Preparation of wetting agent: same as Example 3.

[0137] Wet granulation: same as Example 3.

[0138] Tablet pressing: Use ZP420-19B tablet press machine for large tablets, press tablets at 8000-10000 tablets / h, each tablet is 1g.

[0139] Fluidized bed drying: Pour the compressed tablets into the fluidized bed dryer, adjust the induced draft fan damper to the point where the tablets are slightly lifted, start heating, adjust the inlet temperature to 120°C, and the outlet temperature to 90°C. Dry for 10 minutes and then discharge. Send to the factory for inspection, the moisture content should be less than 4%, if it exceeds the standard, the fluidized bed drying time should be extended.

[0140] The dry tablets are packaged by DPP-80 aluminum-plastic blister packaging machine, with 9 tablets per plate. The finished product is packaged and boxed.

[0141] Example 5: Evaluation of the inhibitory effect of the Chinese medicine composition on hyperuricemia induced by potassium oxonate and hypoxanthine in mice

[0142] 1. Experimental methods

[0143] 60 male Kunming mice, weighing 18-22g, 6 weeks old. After 1 week of adaptive feeding, they were randomly divided into 6 groups: (1) normal group, (2) model group, (3) positive control group: allopurinol 10mg / kg, (4) positive control group: benzbromarone 10mg / kg, (5) Chinese medicine decoction (Chinese medicine decoction in Example 1, the same below): 300mg / kg, (6) Chinese medicine extract (Chinese medicine extract and granules in Example 3, the same below): 300mg / kg. The mice in the normal group were intragastrically and intraperitoneally injected with 0.5% CMC-Na solution, and the mice in the other groups were intraperitoneally injected with 300mg / kg potassium oxonate and 300mg / kg hypoxanthine; 1 hour later, the mice in the normal group and model group were intragastrically administered with 0.5% CMC-Na solution, and the mice in the other groups were intragastrically administered with drugs for 7 consecutive days. One hour after administration on the 7th day, blood was collected from the eyeballs and urine was collected from the bladder. The levels of uric acid, creatinine and urea nitrogen in the serum and urine of the mice were determined according to the kit method.

[0144] 2. Experimental results

[0145] Table 1 Effects of Chinese medicine composition on serum biochemical markers in hyperuricemia mice (mean ± standard deviation)

[0146] Group Serum uric acid (μM) Serum creatinine (μM) Blood urea nitrogen (μM) Normal group 69.40±22.24** 20.70±12.87** 11.30±2.58* Model Group 529.00±92.73 134.00±43.47 39.70±9.42 Allopurinol 111.60±32.19** 128.00±23.94 27.00±8.37 Benzbromarone 349.00±131.80 75.40±16.93 17.00±10.61 Chinese herbal medicine decoction 413.00±68.38 45.60±15.54* 15.70±1.89* Chinese herbal medicine extract 428.60±97.17 40.70±14.94* 15.30±5.31*

[0147] Note: Compared with the model group, **P<0.01, *P<0.05.

[0148] Table 2 Effects of Chinese medicine combination on urine biochemical markers in hyperuricemia mice (mean ± standard deviation)

[0149] Group Urine uric acid (μM) Urine creatinine (μM) Urine urea nitrogen (μM) Normal group 25.00±7.96* 1066.00±154.9 178.40±67.97 Model Group 252.00±52.62 678.00±193.10 61.00±29.54 Allopurinol 79.30±9.97 776.40±121.20 149.60±41.55 Benzbromarone 490.30±90.46* 1856.00±398.40* 282.60±60.05** Chinese herbal medicine decoction 537.30±58.86** 2075.00±423.60* 467.00±51.43** Chinese herbal medicine extract 620.70±120.00** 2311.00±364.90** 519.70±30.74**

[0150] Note: Compared with the model group, **P<0.01, *P<0.05.

[0151] As can be seen above, the allopurinol (positive drug) group, the Chinese herbal decoction and the Chinese herbal extract group all significantly reduced the blood uric acid (SUA) concentration, blood creatinine (SCR) concentration and blood urea nitrogen (SBUN) level in the mice (Table 1, Figure 1 to Figure 3 ). The benzbromarone (positive drug) group, the Chinese herbal decoction prescription, and the Chinese herbal extract prescription group significantly promoted the excretion of uric acid through urine, increased the concentration of urinary uric acid (UUA), promoted the clearance of creatinine through the kidneys, promoted the excretion of urinary creatinine (UCR), and increased the level of urea nitrogen (UBUN) in urine (Table 2, Figure 1 to Figure 3 ).

[0152] Example 6: Evaluation of the effect of Chinese medicine composition on various transport proteins in the kidney of hyperuricemia mice

[0153] 1. Experimental methods

[0154] After the hyperuricemia mice were treated (the mice in the administration group of Example 5), kidney tissues were obtained and homogenized, and RNA and protein were extracted for qRT-PCR and Western blot detection.

[0155] 2. Experimental results

[0156] Compared with the normal group, the renal uric acid transporter URAT1 ( Figure 4 and Figure 8 ), glucose transporter GLUT9 ( Figure 5 and Figure 8 ) expression levels increased, while the expression levels of uric acid secretion proteins OAT1 and OAT3 decreased ( Figure 6 to Figure 8 ), indicating that hypoxanthine and potassium oxonate cause hyperuricemia in mice by increasing the reabsorption of uric acid and reducing uric acid excretion. Compared with the model group, the Chinese medicine decoction and Chinese medicine extract prepared by the present invention can significantly downregulate the levels of URAT1 and GLUT9 genes and proteins, and significantly upregulate the expression of OAT1 and OAT3 proteins ( Figures 4 to 8 ).

[0157] In summary, the Chinese herbal decoction and Chinese herbal extract prepared by the present invention can reduce the reabsorption of uric acid by the kidneys of hyperuricemia mice and promote the excretion of uric acid, thereby exerting the effects of lowering uric acid and resisting hyperuricemia.

Claims

1. A Chinese medicine composition for treating hyperuricemia, characterized in that: By weight, it includes 10-40 parts of chicory leaves, 10-40 parts of astragalus, 4-20 parts of papaya, 4-20 parts of mango leaves, 2-10 parts of eucommia, 2-10 parts of daidai hua, 2-10 parts of galangal, 2-10 parts of gastrodia, 2-10 parts of toona sinensis leaves, 2-10 parts of emblica, 2-10 parts of coix seeds, 2-10 parts of yam, 2-10 parts of corn silk, 1-5 parts of poria, 1-5 parts of galangal and 1-4 parts of zanthoxylum bungeanum.

2. The anti-hyperuricemia Chinese medicine composition according to claim 1, characterized in that: By weight, it includes 15-30 parts of chicory leaves, 15-30 parts of astragalus, 6-10 parts of papaya, 6-10 parts of mango leaves, 3-7 parts of eucommia, 3-7 parts of daidai hua, 3-7 parts of galangal, 3-7 parts of gastrodia, 3-7 parts of toona sinensis leaves, 3-7 parts of emblica, 3-7 parts of coix seeds, 3-7 parts of yam, 3-7 parts of corn silk, 2-4 parts of poria, 2-4 parts of galangal and 2-3 parts of zanthoxylum bungeanum.

3. The anti-hyperuricemia Chinese medicine composition according to claim 1, characterized in that: By weight, it includes 20 parts of chicory leaves, 20 parts of astragalus, 8 parts of papaya, 8 parts of mango leaves, 4 parts of eucommia, 4 parts of daidai hua, 4 parts of galangal, 4 parts of gastrodia, 4 parts of toona sinensis leaves, 4 parts of emblica, 4 parts of coix seeds, 4 parts of yam, 4 parts of corn silk, 3 parts of poria, 3 parts of galangal and 2 parts of Zanthoxylum bungeanum.

4. A method for preparing an extract of the Chinese medicine composition according to claim 1, characterized in that: Choose from any of the following methods: Method 1: Add 1.5 to 3 times the total weight of the medicinal materials in water, soak, extract, and obtain a first extract; add the remaining medicinal residues in water equal to the first extraction, soak, extract, and obtain a second extract; add the remaining medicinal residues in water half the first extraction, soak, and obtain a third extract; combine the three extracts to obtain the extract of the traditional Chinese medicine composition; Method 2: Prepare the extract of each medicinal material, concentrate, and dry to obtain the extract of each medicinal material; or add a pharmaceutically acceptable carrier after concentration to obtain the extract of each medicinal material; mix the extracts of each medicinal material to obtain the extract of the traditional Chinese medicine composition.

5. The preparation method according to claim 4, characterized in that: In the second method, the mass ratios of the medicinal materials slices and extracts of chicory leaves, astragalus, papaya, mango leaves, eucommia, daidai hua, galangal, gastrodia, toona sinensis leaves, emblica, coix seeds, yam, corn silk, poria, galangal, and zanthoxylum bungeanum are 30:1, 30:1, 30:1, 30:1, 30:1, 30:1, 30:1, 30:1, 30:1, 20:1, 10:1, 30:1, 10:1, 30:1, 30:1, and 30:1, respectively.

6. The preparation method according to claim 4, characterized in that: In the second method, the mixing mass ratio of the medicinal material extracts of chicory leaves, astragalus, papaya, mango leaves, eucommia, daikon jasmine, galangal, gastrodia elata, toona sinensis leaves, emblica fructus, coix seeds, yam, corn silk, poria, galangal, and zanthoxylum bungeanum is 20:20:8:8:4:4:4:4:4:4:4:4:4:4:3:3:

2.

7. A pharmaceutical composition, characterized in that An extract comprising the anti-hyperuricemia Chinese medicine composition according to claim 1 and a pharmaceutically acceptable carrier.

8. The pharmaceutical composition according to claim 7, characterized in that The dosage forms include granules, tablets, capsules, ointments, and oral solutions.

9. Use of the anti-hyperuricemia Chinese medicine composition or its extract according to claim 1, or the pharmaceutical composition according to claim 7 in the preparation of a uric acid-lowering drug.

10. The use according to claim 9, characterized in that: The drug is a drug that inhibits uric acid reabsorption and promotes uric acid excretion.

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