CN103919775A - Application of 9-demethylberberine in preparation of hpyerglycemic drug - Google Patents
Application of 9-demethylberberine in preparation of hpyerglycemic drug Download PDFInfo
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- CN103919775A CN103919775A CN201310717235.8A CN201310717235A CN103919775A CN 103919775 A CN103919775 A CN 103919775A CN 201310717235 A CN201310717235 A CN 201310717235A CN 103919775 A CN103919775 A CN 103919775A
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Abstract
The invention provides a hypoglycemic compound 9-demethylberberine. The 9-demethylberberine is derived from a main in-vivo metabolite of natural medicine berberine, and is also named as berberrubine. The researches on animal models with hyperglycemia find that the 9-demethylberberine has good hpyerglycemic effect and has no obvious side effects for 6 weeks of continuous medication. The discovery can lead to discovery of a new hypoglycemic drug, and provides another alternative medicine for clinic treatment of diabetes and related diseases.
Description
Technical field
The present invention relates to there is the 9-demethyl berberine of blood sugar lowering pharmacology effect and potential clinical practice thereof, be specifically related to 9-demethyl berberine and demonstrate good hypoglycemic activity on the sugared animal pattern of height, being expected to becomes a class original new drug by further research and development, for clinical reduction blood glucose and treating diabetes.
Background technology
Diabetes are the main hazard factors that cause cardiovascular and cerebrovascular disease, and relatively a part of diabetics can develop into diabetic nephropathy, causes larger harm.9-demethyl berberine in the present invention derives from natural drug Rhizoma Coptidis, has hypoglycemic activity, has again the very berberine of high security, for main metabolites in berberine body, research finds that 9-demethyl berberine has the hypoglycemic activity stronger than berberine, be expected to by further research and development, become a class original new drug, for clinical blood sugar lowering and treating diabetes.
Summary of the invention
Inventor, by berberine interior metabolism product is studied, finds that in berberine body, one of main metabolites 9-demethyl berberine has good hypoglycemic activity.Be expected to through research for clinical blood sugar lowering and treating diabetes.
Beneficial effect of the present invention
The invention provides 9-demethyl berberine in the application of preparing in hypoglycemic drug, experimental results show that 9-demethyl berberine has good hypoglycemic activity, provides more choices for preparing hypoglycemic drug.
Brief description of the drawings
Accompanying drawing 1 is the affect figure of 9-demethyl berberine on model mice blood sugar level and body weight.Wherein, C is normal feedstuff matched group; H is model group (giving CMC-Na solution); BBR is that berberine gavage group (120mg/Kgd), M1 (i.g.) are 9-demethyl berberine gavage group (40mg/Kgd); M1 (i.p.) is 9-demethyl berberine lumbar injection group (20mg/Kgd).* P<0.05, * * P<0.01vs hyperlipidemia model group.
Detailed description of the invention
The present invention carries out detailed explanation by the following examples, but and does not mean that the present invention only limits to this.
9-demethyl berberine hypoglycemic activity experimentation
Example 9-demethyl berberine hypoglycemic activity
Employing C57BL/6 mice (30, purchased from Military Medical Science Institute, body weight 18 ± 2g) test.With AIN93 standard feed (by calorific value calculation, fatty 10%, carbohydrate 75.9%, protein 14.1%, 3601 kcal/kg) and feeding standard environment under (free diet and drinking-water, day alternates with night, each 12 hours), adaptability is raised one week.Subsequently, be divided at random 5 groups by body weight, one group is continued to give normal feedstuff, other four groups all give high calorie energy feed (by calorific value calculation, fatty 60%, carbohydrate 25.9%, protein 14.1%, heat is 5018 kcal/kg) (Nantong Te Luofei feed technology company limited), all rats all can freely drink water.Above-mentioned 5 treated animal the same terms are raised, and during to 3 weeks, get blood, and separation of serum is measured blood glucose according to test kit explanation (the safe clinical reagent of Beijing Northization company limited), confirm hyperglycemia model success.
Hyperglycemia treated animal is divided into four groups, be divided into blank gavage group (giving CMC-Na blank solution), berberine gavage group (BBR, 120mg/Kgd), 9-demethyl berberine gavage group (40mg/Kgd), 9-demethyl berberine lumbar injection group (20mg/Kgd), within every 3 days, weigh once.Get blood respectively at after administration 6 weeks, separation of serum, measures blood glucose, and carries out statistical analysis (Student ' s t test, table 1, Fig. 1).
Measurement result shows, 3 weeks high calorie energy feeds of model group process feeding, and animal blood glucose obviously raises, and modeling success is described.And berberine gavage, 9-demethyl berberine gavage and lumbar injection have all significantly reduced Mouse Weight and blood glucose parameter.Show that 9-demethyl berberine has good hypoglycemic activity.
After the administration of table 19-demethyl berberine, mice index of correlation changes (n=6)
* P<0.05, the high sugared model group of * * P<0.01vs
#p<0.05,
##p<0.01vs matched group.
Claims (8)
1. be used for the treatment of diabetes and relevant disease suc as formula the 9-demethyl berberine shown in I.
Molecular formula: [C
19h
16nO
4]+; Molecular weight: 322.33
Formula I
2. except the 9-demethyl berberine in claim 1, can also be in conjunction with the salt forming with acceptable acid pharmaceutically.Pharmaceutically acceptable acid can be organic acid, mineral acid, aminoacid.The kind of acid is as all kinds of organic and mineral acids such as citric acid, maleic acid, succinic acid, fumaric acid, malic acid, hydrobromic acid, nitric acid, tartaric acid, oxalic acid, tannic acid, methanesulfonic acid, pantothenic acid, hydrochloric acid, sulphuric acid, sulfurous acid, pyrosulfurous acid, hydrosulphuric acid, phosphoric acid, dihydrogen phosphoric acid, sulfurous acid, acetone acid, nicotinic acid, lactic acid, orotic acid, ascorbic acid, folic acid, formic acid, acetic acid, propanoic acid, butanoic acid, valeric acid, glyceric acid, glycolics.And aminoacid, as taurine, glycine, arginine, glutamic acid, lysine etc.
3. a compositions for hypoglycemic drug, by salt described in the 9-demethyl berberine shown in formula I or claim 2 and one or more pharmaceutically acceptable carrier make.
4. according to the pharmaceutical composition described in salt in claim 2 and 3, it is characterized in that: also contain one or more other blood-sugar decreasing actives.
5. pharmaceutical composition according to claim 4, is characterized in that: in pharmaceutical composition, the purity of formula I compound is greater than 95%.
6. according to the pharmaceutical composition described in any one in claim 5, it is characterized in that: compositions is made into acceptable dosage form clinically, comprise the various dosage forms of oral and parenteral form.For example tablet, capsule, oral liquid, syrup, granule, drop pill, oral cavity disintegration tablet, slow releasing tablet, patch, micropill, microcapsule, liposome, microsphere, sustained-release preparation; Controlled release preparation; All kinds of solids, semisolid, liquid, Emulsion or the mixed suspension preparations such as liquid drugs injection, freeze-dried powder, aseptic powder injection, transfusion.
7. pharmaceutical composition according to claim 6, is characterized in that: described pharmaceutically acceptable carrier is selected from filler, binding agent, lubricant, disintegrating agent, cosolvent, absorption carrier; Solvent, antioxidant, adsorbent, osmotic pressure regulator, pH adjusting agent.
8. according to the purposes in claim 1, except diabetic, can also be the hyperglycemia causing because of a variety of causes, the patient of carbohydrate metabolism disturbance.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310717235.8A CN103919775A (en) | 2013-12-20 | 2013-12-20 | Application of 9-demethylberberine in preparation of hpyerglycemic drug |
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| CN201310717235.8A CN103919775A (en) | 2013-12-20 | 2013-12-20 | Application of 9-demethylberberine in preparation of hpyerglycemic drug |
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| CN103919775A true CN103919775A (en) | 2014-07-16 |
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105497028A (en) * | 2015-12-15 | 2016-04-20 | 上海壹志医药科技有限公司 | Medicinal application of berberrubine |
| CN113616647A (en) * | 2020-05-09 | 2021-11-09 | 中国医学科学院药物研究所 | Use of berberine in treating glucocorticoid-induced metabolic disorder |
| CN115068473A (en) * | 2021-03-15 | 2022-09-20 | 中国医学科学院药物研究所 | Application of berberine type pyridine carboxylic acid quaternary ammonium salt compound in resisting virus infection diseases |
| CN115073447A (en) * | 2021-03-15 | 2022-09-20 | 中国医学科学院药物研究所 | Berberine type pyridine carboxylic acid quaternary ammonium salt compound and application thereof in preparing medicines |
| CN115073446A (en) * | 2021-03-15 | 2022-09-20 | 中国医学科学院药物研究所 | Berberine type alkaloid oxidized pyrazine formic acid quaternary ammonium salt and application thereof in preparing medicines |
| WO2022194136A1 (en) * | 2021-03-15 | 2022-09-22 | 中国医学科学院药物研究所 | Diphenyl alkane compound and preparation method therefor, and pharmaceutical composition and use thereof |
| CN116139134A (en) * | 2023-03-29 | 2023-05-23 | 首都医科大学附属北京同仁医院 | Application of berberine metabolite in preparation of medicine for stimulating GLP-1 secretion |
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| CN101327214A (en) * | 2008-07-18 | 2008-12-24 | 中国药科大学 | Medicine use of isoquinoline alkaloids as tissue factor inhibitor |
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2013
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101327214A (en) * | 2008-07-18 | 2008-12-24 | 中国药科大学 | Medicine use of isoquinoline alkaloids as tissue factor inhibitor |
Non-Patent Citations (3)
| Title |
|---|
| HONG-YING CHEN等: "Cytotoxicity and antihyperglycemic effect of minor constituents from Rhizoma Coptis in HepG2 cells", 《FITOTERAPIA》 * |
| 曹阳 等: "原小檗碱类化合物的药理作用研究进展", 《现代药物与临床》 * |
| 杨勇 等: "小檗红碱的化学与药理", 《现代生物医学进展》 * |
Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105497028A (en) * | 2015-12-15 | 2016-04-20 | 上海壹志医药科技有限公司 | Medicinal application of berberrubine |
| CN113616647A (en) * | 2020-05-09 | 2021-11-09 | 中国医学科学院药物研究所 | Use of berberine in treating glucocorticoid-induced metabolic disorder |
| CN115068473A (en) * | 2021-03-15 | 2022-09-20 | 中国医学科学院药物研究所 | Application of berberine type pyridine carboxylic acid quaternary ammonium salt compound in resisting virus infection diseases |
| CN115073447A (en) * | 2021-03-15 | 2022-09-20 | 中国医学科学院药物研究所 | Berberine type pyridine carboxylic acid quaternary ammonium salt compound and application thereof in preparing medicines |
| CN115073446A (en) * | 2021-03-15 | 2022-09-20 | 中国医学科学院药物研究所 | Berberine type alkaloid oxidized pyrazine formic acid quaternary ammonium salt and application thereof in preparing medicines |
| WO2022194136A1 (en) * | 2021-03-15 | 2022-09-22 | 中国医学科学院药物研究所 | Diphenyl alkane compound and preparation method therefor, and pharmaceutical composition and use thereof |
| CN115073447B (en) * | 2021-03-15 | 2024-06-21 | 中国医学科学院药物研究所 | Berberine type pyridine carboxylic acid quaternary ammonium salt compound and application thereof in preparation of medicines |
| CN115073446B (en) * | 2021-03-15 | 2024-06-21 | 中国医学科学院药物研究所 | Berberine type alkaloid oxidized pyrazinecarboxylic acid quaternary ammonium salt and application thereof in preparation of medicines |
| CN115068473B (en) * | 2021-03-15 | 2024-09-17 | 中国医学科学院药物研究所 | Application of berberine type alkaloid pyridine carboxylic acid quaternary ammonium salt compound in preparation of medicine for resisting virus infection |
| CN116139134A (en) * | 2023-03-29 | 2023-05-23 | 首都医科大学附属北京同仁医院 | Application of berberine metabolite in preparation of medicine for stimulating GLP-1 secretion |
| CN116139134B (en) * | 2023-03-29 | 2024-06-25 | 首都医科大学附属北京同仁医院 | Application of berberine metabolite in preparation of medicine for stimulating GLP-1 secretion |
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