CN111202728A - Application of calycosin in preparing medicine for preventing, relieving and/or treating hyperuricemia - Google Patents
Application of calycosin in preparing medicine for preventing, relieving and/or treating hyperuricemia Download PDFInfo
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- CN111202728A CN111202728A CN202010098889.7A CN202010098889A CN111202728A CN 111202728 A CN111202728 A CN 111202728A CN 202010098889 A CN202010098889 A CN 202010098889A CN 111202728 A CN111202728 A CN 111202728A
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric agents
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Abstract
The invention belongs to the field of medicines, researches an active compound for treating hyperuricemia, and finds that calycosin has a certain treatment effect on the hyperuricemia through experimental research. The drug effect component of the invention is a monomeric compound, and animal experiments show that the compound has stronger effect of reducing the content of Uric Acid (UA), urea nitrogen (BUN), creatinine (SCr) and Xanthine Oxidase (XOD) in a mouse body. The invention utilizes hyperuricemia animal models to prove that calycosin has obvious treatment effect on hyperuricemia.
Description
Technical Field
The invention relates to the technical field of medicines, in particular to application of calycosin, and particularly relates to application of calycosin in treating hyperuricemia.
Background
Hyperuricemia is a metabolic disease in which uric acid production is increased and excretion is decreased due to purine metabolic disorder. The disease is easy to separate out and deposit urate crystals in vivo, which causes gout and induces a plurality of serious diseases such as myocardial infarction, coronary heart disease, diabetes, hyperlipidemia, metabolic syndrome, chronic kidney disease and the like.
The economy of China is rapidly developed, meanwhile, the dietary habits of people are greatly changed, and the number of patients with hyperuricemia caused by poor dietary habits is increased year by year. It is reported that about 1.2 hundred million patients with hyperuricemia in China account for about 10% of the total number of people in China. This condition has become an important disease threatening human health. Therefore, the development of a highly effective drug for treating hyperuricemia is imminent.
The current effective means for treating hyperuricemia by using drugs include inhibiting uric acid production, promoting uric acid excretion and the like. Although drugs for inhibiting uric acid production (allopurinol, febuxostat and the like) and drugs for promoting uric acid excretion (probenecid, benzbromarone and the like) have good treatment effects, certain potential safety hazards exist, and the health of organs of patients is threatened. If a natural medicine which can be used for treating hyperuricemia can be found, the generation of toxic and side effects can be reduced to the maximum extent.
The tetrandra and astragalus decoction has a good curative effect on hyperuricemia, but the effective components of the tetrandra and astragalus decoction are not clear, the micro analysis on drug effect substances is lacked, and related reports that the effective components are used for treating the hyperuricemia are not available. The treatment effect of the fangji Huangqi decoction on hyperuricemia is limited, and certain individual differences exist. The separation and extraction of the effective components of the traditional Chinese medicine can improve the treatment effect, is a hotspot and trend of the international development of the traditional Chinese medicine research, and has important significance for developing new medicines with less components, controllable quality and definite mechanism.
Disclosure of Invention
In view of the above-described situation, an object of the present invention is to provide an active substance effective for the treatment of hyperuricemia from the viewpoint of the conventional art.
The technical scheme of the invention is as follows:
the first object of the present invention is to provide the use of calycosin or a pharmaceutically acceptable salt thereof for the preparation of a medicament for the prevention, alleviation and/or treatment of hyperuricemia.
Further, the active ingredient of the medicament is calycosin or pharmaceutically acceptable salts thereof.
Furthermore, the medicine also comprises pharmaceutically acceptable auxiliary materials or auxiliary components.
Furthermore, the dosage form of the medicine is oral preparation or other dosage forms, such as injection and the like.
Further, the oral preparation is powder, tablets, granules, capsules, dripping pills, paste or powder.
Further, the drug for preventing, alleviating and/or treating hyperuricemia is capable of alleviating a condition of weight loss of a patient caused by hyperuricemia.
Further, the drug for preventing, alleviating and/or treating hyperuricemia is capable of alleviating liver atrophy caused by hyperuricemia.
Further, the drug for preventing, alleviating and/or treating hyperuricemia can alleviate splenomegaly caused by hyperuricemia.
Further, the medicament for preventing, alleviating and/or treating hyperuricemia can reduce the content of uric acid, urea nitrogen and xanthine oxidase in a hyperuricemia patient, and/or reduce the content of creatinine in the hyperuricemia patient.
The second object of the present invention is to provide a drug for preventing, alleviating and/or treating hyperuricemia, the active ingredient of the drug being calycosin or a pharmaceutically acceptable salt thereof.
Furthermore, the medicine also comprises pharmaceutically acceptable auxiliary materials or auxiliary components.
Furthermore, the dosage form of the medicine is oral preparation or other dosage forms, such as injection and the like.
Further, the oral preparation is powder, tablets, granules, capsules, dripping pills, paste or powder.
Further, the drug for preventing, alleviating and/or treating hyperuricemia is capable of alleviating a condition of weight loss of a patient caused by hyperuricemia.
Further, the drug for preventing, alleviating and/or treating hyperuricemia is capable of alleviating liver atrophy caused by hyperuricemia.
Further, the drug for preventing, alleviating and/or treating hyperuricemia can alleviate splenomegaly caused by hyperuricemia.
Further, the medicament for preventing, alleviating and/or treating hyperuricemia can reduce the content of uric acid, urea nitrogen and xanthine oxidase in a hyperuricemia patient, and/or reduce the content of creatinine in the hyperuricemia patient.
Calycosin has the following structural formula and molecular formula:
structural formula (xvi):
the molecular formula is as follows: c16H12O5
Naming: 7-hydroxy-3- (3-hydroxy-4-methoxyphenyl) chromen-4-one
English name: calycosin
Molecular weight: 284.26348
CAS number: 20575-57-9
Introduction of calycosin: is stable under normal temperature and environment, is white crystal, has the functions of protecting heart and cerebral vessels, liver, kidney and lung, protecting brain cells, improving memory, relaxing vascular smooth muscle, resisting bacteria, inhibiting virus, reducing blood fat and blood sugar, reducing diabetic complication and the like. The product can be isolated from Astragalus membranaceus, and is also found in Mongolian red clover and clover (red clover).
The technical scheme of the invention has the following beneficial effects:
the invention discovers that the effective component of calycosin in the tetrandra and astragalus decoction has better effect on treating hyperuricemia when the tetrandra and astragalus decoction is used for treating the hyperuricemia.
Through experimental research, calycosin can be used for treating hyperuricemia and also has an improvement effect on gout caused by excessive uric acid content in vivo, and has a good development prospect. The calycosin oral preparation is developed by taking the core overall view of the theory of traditional Chinese medicine as guidance, taking human overall factors as the basis and adopting the innovative ideas of tonifying qi, dispelling wind, strengthening spleen and promoting diuresis.
The present inventors found that calycosin has an excellent effect of reducing the contents of Uric Acid (UA), urea nitrogen (BUN), creatinine (SCR) and Xanthine Oxidase (XOD) in vivo, and is useful as a drug for treating all diseases caused by an excess of uric acid in vivo, thereby completing the present invention.
The research of the invention finds that calycosin has obvious curative effect in relieving the liver atrophy, splenomegaly and weight loss caused by hyperuricemia.
The invention has the advantage of providing the calycosin which is a compound originated from the traditional Chinese medicine and can be used for treating hyperuricemia. Provides a new idea and method for treating hyperuricemia.
Detailed Description
The following examples are presented to enable those skilled in the art to more fully understand the present invention and are not intended to limit the invention in any way. The examples, in which specific conditions are not specified, were conducted under conventional conditions or conditions recommended by the manufacturer. The reagents or instruments used are not indicated by the manufacturer, and are all conventional products available commercially.
Experimental animals: kunming mice, SPF grade 20. + -.2 g, male.
Experimental drugs: potassium oxamate (brand: aladin, product number: P137112), allopurinol (brand: aladin, product number: A105386), calycosin (Shanghai Shifeng biological products, Inc.), Stephania tetrandra, Astragalus membranaceus, Glycyrrhiza uralensis, and Atractylodes macrocephala.
An experimental model: mouse hyperuricemia model.
The experimental method comprises the following steps: the Kunming mice were randomly grouped and numbered, and 7 mice in each group were a normal group, a model group, a positive group, a calycosin low-dose group, and a calycosin high-dose group, respectively. All mice were gavaged for two weeks, once a day. One hour after the last administration, the eyeball was picked up and blood was taken out and serum was separated, and immediately after the blood was taken, cervical dislocation was sacrificed and relevant organs were separated. And (6) carrying out relevant data determination and analysis.
The experimental steps are as follows:
1. kunming mice are self-adaptively raised for one week, and divided into a normal group, a model group, a positive group, a calycosin low-dose group and a calycosin high-dose group during the period, and are marked and weighed.
2. Preparing the medicine: uniformly dispersing potassium oxonate (300mg/kg) with the purity of more than or equal to 98 percent in physiological saline; positive drugs: uniformly dispersing allopurinol (10mg/kg) with the purity of more than or equal to 98 percent in physiological saline; uniformly dispersing calycosin (15mg/kg, 40mg/kg) with purity of more than or equal to 98% in physiological saline; decoction of radix Stephaniae Tetrandrae and radix astragali: weighing 12g of radix stephaniae tetrandrae, 15g of astragalus membranaceus, 9g of bighead atractylodes rhizome and 6g of liquorice, placing the mixture in a 1L round-bottom flask, soaking for one hour, filtering, then refluxing and concentrating to 60ml, cooling, and placing the mixture in a refrigerator for later use.
3. The model group, the positive group, the decoction group and each medicine group are respectively modeled according to weight gavage potassium oxonate (300mg/kg), and the normal group is gavage with equal amount of normal saline. Thirty minutes after molding, the model group was perfused with gastric physiological saline, the positive group was perfused with gastric allopurinol (10mg/kg), the decoction group was perfused with gastric tetrandra and astragalus decoction (10ml/kg), and two groups of the drugs were separately perfused with two groups of the test compounds (low dose of calycosin 15mg/kg and high dose of 40mg/kg) at different doses. Weigh daily and record data.
4. The administration was continued for two weeks, one hour after the last administration.
5. The mice were bled from the eyes to obtain about 1ml of blood. Centrifuging at 2500r/min for 10min at 4 deg.C, collecting supernatant, and freezing in refrigerator at-20 deg.C in 200 μ L/tube for detecting corresponding biochemical indexes including Uric Acid (UA), urea nitrogen (BUN), and creatinine (SCR).
6. After blood sampling, cervical dislocation was immediately sacrificed and heart, liver, spleen, lung, kidney, brain were dissected and separated on an ice bench and weighed for recording. A suitable amount of liver tissue was taken to prepare a homogenate and the content of Xanthine Oxidase (XOD) in the liver was measured.
7. The experimental results are as follows:
table one: effect of Calycosin on body weight
Watch 1
Data result use
Is represented by the formula, n is 7
In comparison with the normal group,#P<0.05，##P<0.01，###P<0.001
in comparison with the set of models,*P<0.05，**P<0.01，***P<0.001
the data in table one are mean ± standard deviation of the body weight of 7 mice per group, tested for variance (P) with LSD. As can be seen from the table: the tendency of mice to lose weight with high doses of test compound was reduced, indicating that high doses of calycosin can alleviate the condition of weight loss in hyperuricemia patients.
Table two: the ratio of visceral to brain coefficients of four groups of mice was compared
Watch two
Data result use
Is represented by the formula, n is 7
In comparison with the normal group,#P<0.05，##P<0.01，###P<0.001
comparison with model group，*P<0.05，**P<0.01，***P<0.001
The data in table two are comparisons of the brain coefficients of 7 mice per group, tested for variance (P) with LSD. As can be seen from the table: hyperuricemia causes significant difference between the liver, spleen and brain of the diseased mouse compared with the normal group and the model group; the calycosin can remarkably relieve the conditions of liver atrophy and splenomegaly caused by hyperuricemia at high and low doses. The difference between the calycosin high-dose group and the model group is larger than that between the decoction group and the model group, and the data show that the single-drug calycosin has better curative effect on visceral problems caused by hyperuricemia than the traditional tetrandra and astragalus decoction.
Table three: organ coefficient comparison of 4 groups of mice
Watch III
Data result use
Is represented by the formula, n is 7
In comparison with the normal group,#P<0.05，##P<0.01，###P<0.001
in comparison with the set of models,*P<0.05，**P<0.01，***P<0.001
the data in table three are comparisons of organ coefficients of 7 mice per group, and variance (P) tests were performed using LSD. From the third table, it can be seen that: the hyperuricemia causes the ratio of the liver, the spleen, the lung and the body weight of the sick mice to be obviously different from that of the normal group; the high dose of calycosin can obviously relieve the symptoms of splenomegaly of patients with hyperuricemia, and has better effect compared with the traditional tetrandra and astragalus decoction.
Table four: biochemical index comparison of 4 groups of mice
Table four:
data result use
Is represented by the formula, n is 7
In comparison with the normal group,#P<0.05，##P<0.01，###P<0.001
in comparison with the set of models,*P<0.05，**P<0.01，***P<0.001
the data in table four are comparisons of four biochemical indicators for uric acid, creatinine, xanthine oxidase and urea nitrogen in 7 mice per group, and variance (P) test using LSD. Hyperuricemia causes uric acid, creatinine and urea nitrogen in blood serum of sick mice, and the content of xanthine oxidase in livers is remarkably increased; the content of uric acid, urea nitrogen and xanthine oxidase of hyperuricemia patients can be obviously reduced by the high and low dosages of calycosin, and the creatinine content can be obviously reduced by the high dosage of calycosin. Compared with allopurinol as positive drug and conventional Fangji Huangqi decoction, calycosin has effect of reducing xanthine oxidase.
The results show that calycosin can be used for preparing medicines for reducing uric acid, creatinine and urea nitrogen or treating hyperuricemia.
The therapeutic effect is better with the increase of the dosage of the calycosin, which shows that the calycosin has dosage dependence, and the dosage can be properly changed to obtain better therapeutic effect.
The therapeutic effect of calycosin is superior to that of a positive control medicament in reducing uric acid, urea nitrogen and creatinine in vivo, and the calycosin has a good development prospect.
The above is only a preferred embodiment of the present invention, and it should be noted that the above preferred embodiment should not be considered as limiting the present invention, and the protection scope of the present invention should be subject to the scope defined by the claims. It will be apparent to those skilled in the art that various modifications and adaptations can be made without departing from the spirit and scope of the invention, and such modifications and adaptations are intended to be within the scope of the invention.
Claims (6)
1. Use of calycosin or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for the prevention, alleviation and/or treatment of hyperuricemia.
2. The use of claim 1, wherein the active ingredient of the medicament is calycosin or a pharmaceutically acceptable salt thereof.
3. The use of claim 1, wherein the medicament further comprises a pharmaceutically acceptable adjuvant or auxiliary ingredient.
4. The use of claim 1, wherein the medicament is in the form of an oral formulation or an injectable formulation.
5. The use of claim 4, wherein the oral formulation is a powder, tablet, granule, capsule, drop pill, paste or powder.
6. A medicament for preventing, alleviating and/or treating hyperuricemia, wherein the active ingredient of the medicament is calycosin or a pharmaceutically acceptable salt thereof.
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| Application Number | Priority Date | Filing Date | Title |
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| CN202010098889.7A CN111202728A (en) | 2020-02-18 | 2020-02-18 | Application of calycosin in preparing medicine for preventing, relieving and/or treating hyperuricemia |
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Non-Patent Citations (2)
| Title |
|---|
| DE-HONG YU等: "Protection of PC12 Cells against Superoxide-induced Damage by Isoflavonoids from Astragalus mongholicus", 《BIOMEDICAL AND ENVIRONMENTAL SCIENCES》 * |
| 吴开春等: "《内科学》", 30 June 2017, 北京：中国医药科技出版社 * |
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Application publication date: 20200529 |