CN103919773A - Application of 9-demethylberberine in preparation of hypolipidemic drug - Google Patents
Application of 9-demethylberberine in preparation of hypolipidemic drug Download PDFInfo
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- CN103919773A CN103919773A CN201310717233.9A CN201310717233A CN103919773A CN 103919773 A CN103919773 A CN 103919773A CN 201310717233 A CN201310717233 A CN 201310717233A CN 103919773 A CN103919773 A CN 103919773A
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Abstract
The invention provides a hypolipidemic 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 model animals with hyperlipidemia find that the 9-demethylberberine has good drug effects of reducing cholesterol, triglyceride, low density lipoprotein (LDL) and the like, and has no obvious side effects for 6 weeks of continuous medication. The discovery can lead to discovery of a new hypolipidemic drug, and provides another alternative medicine for clinic treatment of hyperlipidemia, lipid metabolism disorder and high fat and obese patients and related people wanting to lose weight.
Description
Technical field
The present invention relates to there is the 9-demethyl berberine of blood fat reducing pharmacological action and potential clinical practice thereof, be specifically related to 9-demethyl berberine and on hyperlipidemia model animal, demonstrate good effect for reducing fat, being expected to becomes a class original new drug by further research and development, for clinical blood fat reducing, regulate lipid metabolism abnormal and lose weight for obese people.
Background technology
Hyperlipidemia is the main hazard factor that causes cardiovascular and cerebrovascular disease, is a key factor of harm humans health.Although the medicine such as Statins has good effect for reducing fat clinically, may there is the toxic and side effects such as hepatotoxicity, rhabdomyolysis in life-time service, and liver Chinese medicine metabolic enzyme is had to considerable influence.And the expression of liver Chinese medicine metabolic enzyme may exert an influence to pharmacokinetics in the body of combination with medication with active variation, cause drug interaction and cause drug effect to reduce or occur toxic and side effects.9-demethyl berberine in the present invention derives from natural drug Rhizoma Coptidis, has effect for reducing fat, has again the very berberine of high security, for main metabolites in berberine body, research finds that 9-demethyl berberine has the effect for reducing fat stronger than berberine, be expected to by further research and development, become a class original new drug, for clinical blood fat reducing, regulate lipid metabolism abnormal and and lose weight for obese people.
Summary of the invention
Inventor, by berberine interior metabolism product is studied, finds that one of berberine interior metabolism product 9-demethyl berberine has good effect for reducing blood fat.Be expected to through research for clinical reduction blood fat, fat-reducing etc.
Beneficial effect of the present invention
The invention provides the application of 9-demethyl berberine in preparing blood lipid-lowering medicine, experimental results show that 9-demethyl berberine has good effect for reducing fat, provides more choices for preparing fat-reducing medicament.
Accompanying drawing explanation
Accompanying drawing 1 is that 9-demethyl berberine is to high blood lipid model mice effect for reducing fat figure.Wherein, C is normal feedstuff matched group; H is high lipid food 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) .TG: total triglyceride in serum; TC: T-CHOL; HDL-C: low-density lipoprotein cholesterol LDL-C: low-density lipoprotein cholesterol.* P<0.05, * * P<0.01vs hyperlipidemia model group.
The specific embodiment
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 effect for reducing fat experimentation
Example 9-demethyl berberine effect for reducing fat
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 under feeding standard environment (free diet and drinking-water, day alternates with night, each 12 hours), adaptability is raised one week.Subsequently, by body weight, be divided at random 5 groups, one group is continued to give normal feedstuff, other four groups all give high lipid food (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, during to 3 weeks, get blood, separation of serum slurry, according to test kit explanation (the safe clinical reagent of Beijing Northization company limited), measure total triglyceride (TG), T-CHOL (TC), HDL-C (HDL) and low-density lipoprotein cholesterol (LDL) in serum, confirm hyperlipidemia model success.
High fat 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.Respectively within after administration 6 weeks, getting blood, separation of serum, with said method, measure total triglyceride (TG), T-CHOL (TC), HDL-C (HDL) and low-density lipoprotein cholesterol (LDL) in serum, and carry out statistical analysis (Student ' sttest, table 1, Fig. 1).
Measurement result shows, 3 weeks high lipid foods of model group process feeding, and animal lipid obviously raises, and modeling success is described.And berberine gavage, 9-demethyl berberine gavage and lumbar injection have all significantly reduced Mouse Weight and lipid parameter, as total triglyceride (TG), T-CHOL (TC), low-density lipoprotein cholesterol (LDL) in serum.Show that 9-demethyl berberine has good effect for reducing fat.
After the administration of table 1 9-demethyl berberine, mice index of correlation changes (n=6)
* P<0.05, * * P<0.01vs hyperlipidemia model group
#p<0.05vs matched group.
Claims (8)
1. suc as formula the 9-demethyl berberine shown in I, be used for the treatment of hyperlipidemia and relevant disease.
Molecular formula: [C
19h
16nO
4]+; Molecular weight: 322.33
Formula I
2. except the 9-demethyl berberine in claim 1, can also be to be combined formed salt 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 blood lipid-lowering medicine, 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 hypolipidemic activity compositions.
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 can be used for hyperlipidemia patient, can also cause blood fat, disorders of lipid metabolism patient for diseases such as obesity, diabetes, and other crowds that need fat-reducing, blood fat reducing.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310717233.9A CN103919773A (en) | 2013-12-20 | 2013-12-20 | Application of 9-demethylberberine in preparation of hypolipidemic drug |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201310717233.9A CN103919773A (en) | 2013-12-20 | 2013-12-20 | Application of 9-demethylberberine in preparation of hypolipidemic drug |
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| CN103919773A true CN103919773A (en) | 2014-07-16 |
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| CN201310717233.9A Pending CN103919773A (en) | 2013-12-20 | 2013-12-20 | Application of 9-demethylberberine in preparation of hypolipidemic drug |
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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 |
| CN111493080A (en) * | 2017-11-20 | 2020-08-07 | 华南农业大学 | Application of berberine compounds as herbicide |
| CN112641780A (en) * | 2021-01-19 | 2021-04-13 | 山东省中医药研究院 | Application of berberberrubine in preparing anti-insomnia medicine |
| 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 |
-
2013
- 2013-12-20 CN CN201310717233.9A patent/CN103919773A/en active Pending
Non-Patent Citations (2)
| Title |
|---|
| SHIJIE CAO ET AL.: ""Berberine metabolites exhibit triglyceride-lowering effects via activation of AMP-activated protein kinase in Hep G2 cells"", 《JOURNAL OF ETHNOPHARMACOLOGY》 * |
| SHIJIE CAO ET AL.: ""Berberine metabolites exhibit triglyceride-lowering effects via activation of AMP-activated protein kinase in Hep G2 cells"", 《JOURNAL OF ETHNOPHARMACOLOGY》, vol. 149, 27 July 2013 (2013-07-27), pages 576 - 582, XP028698009, DOI: doi:10.1016/j.jep.2013.07.025 * |
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 |
| CN111493080A (en) * | 2017-11-20 | 2020-08-07 | 华南农业大学 | Application of berberine compounds as herbicide |
| CN111493080B (en) * | 2017-11-20 | 2021-07-09 | 华南农业大学 | Application of berberine compounds as herbicide |
| CN112641780A (en) * | 2021-01-19 | 2021-04-13 | 山东省中医药研究院 | Application of berberberrubine in preparing anti-insomnia medicine |
| 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 |
| 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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Application publication date: 20140716 |