CN103989677A - Use of demethyleneberberine in preparation of blood sugar-reduction drug - Google Patents
Use of demethyleneberberine in preparation of blood sugar-reduction drug Download PDFInfo
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- CN103989677A CN103989677A CN201310717232.4A CN201310717232A CN103989677A CN 103989677 A CN103989677 A CN 103989677A CN 201310717232 A CN201310717232 A CN 201310717232A CN 103989677 A CN103989677 A CN 103989677A
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Abstract
The invention provides a compound having a blood sugar-reduction effect, and the compound is demethyleneberberine. Demethyleneberberine is extracted from an in-vivo metabolite of natural drug berberine. A hyperglycemia model animal research shows that demethyleneberberine has good blood sugar-reduction effects, and after continuous administration for six weeks, obvious toxic or side effect is not produced. Through discovery of the use, a novel blood sugar-reduction drug can be produced and provides an optional drug for clinical treatment on diabetes and related diseases.
Description
Technical field
What the present invention relates to have the effect of blood sugar lowering pharmacology goes methylene berberine and potential clinical practice thereof, be specifically related to methylene 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.Going methylene berberine to derive from natural drug Rhizoma Coptidis, there is hypoglycemic activity, have again the very berberine of high security in the present invention, for main metabolites in berberine body, research is found to go methylene berberine to have stronger hypoglycemic activity, there is no obvious toxic and side effects.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 goes methylene berberine to have 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 the application of methylene berberine in preparing hypoglycemic drug, experimental results show that methylene berberine has good hypoglycemic activity, for preparing hypoglycemic drug, provide more choices.
Accompanying drawing explanation
Accompanying drawing 1 is for removing the affect figure of methylene berberine on model mice blood sugar level and body weight.C is normal feedstuff matched group; H is model group (giving CMC-Na solution); BBR is that berberine gavage group (120mg/Kgd), M2 (i.g.) are for going methylene berberine gavage group (120mg/Kgd); M2 (i.p.) is for going methylene berberine lumbar injection group (20mg/Kgd).* 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.
Go methylene berberine hypoglycemic activity experimentation
Example removes methylene 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 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 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), go methylene berberine gavage group (120mg/Kgd), go methylene 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 carry 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 pattern blood glucose obviously raises, and modeling success is described.And berberine gavage, go methylene berberine gavage and lumbar injection all significantly to reduce Mouse Weight and blood glucose parameter.Showing goes methylene berberine to have good hypoglycemic activity.
After table 1 goes the administration of methylene 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. suc as formula the methylene berberine that goes shown in I, be used for the treatment of diabetes and relevant disease.
Molecular formula: [C
19h
18nO
4]+; Molecular weight: 324.35
Formula I.
2. except removing methylene 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 hypoglycemic drug, by shown in formula I go described in methylene berberine or claim 2 salt 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 |
|---|---|---|---|
| CN201310717232.4A CN103989677A (en) | 2013-12-20 | 2013-12-20 | Use of demethyleneberberine in preparation of blood sugar-reduction drug |
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| CN201310717232.4A CN103989677A (en) | 2013-12-20 | 2013-12-20 | Use of demethyleneberberine in preparation of blood sugar-reduction drug |
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Cited By (8)
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| CN104860940A (en) * | 2015-05-22 | 2015-08-26 | 湖南省中医药研究院中药研究所 | Valproate and protoberberine compounds, preparation method and application |
| WO2016015634A1 (en) | 2014-07-29 | 2016-02-04 | Shenzhen Hightide Biopharmaceutical, Ltd. | Berberine salts, ursodeoxycholic salts and combinations, methods of preparation and application thereof |
| WO2016161921A1 (en) * | 2015-04-06 | 2016-10-13 | Shenzhen Hightide Biopharmaceutical, Ltd. | Conjugate compounds of ursodeoxycholic, berberine or l-carnitine, and compositions and methods thereof |
| EP3456328A4 (en) * | 2016-05-10 | 2020-02-26 | Shenzhen Hightide Biopharmaceutical., Ltd. | Composition, and application and pharmaceutical preparation thereof |
| 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 |
| 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 |
| 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 |
-
2013
- 2013-12-20 CN CN201310717232.4A patent/CN103989677A/en active Pending
Cited By (15)
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| US10988471B2 (en) | 2014-07-29 | 2021-04-27 | Shenzhen Hightide Biopharmaceutical, Ltd. | Pharmaceutical composition comprising berberine ursodeoxycholic acid salt for the treatment of various diseases or disorders |
| WO2016015634A1 (en) | 2014-07-29 | 2016-02-04 | Shenzhen Hightide Biopharmaceutical, Ltd. | Berberine salts, ursodeoxycholic salts and combinations, methods of preparation and application thereof |
| US11685735B2 (en) | 2014-07-29 | 2023-06-27 | Shenzhen Hightide Biopharmaceutical, Ltd. | Pharmaceutical composition comprising berberine salts for the treatment of various diseases or disorders |
| US10301303B2 (en) | 2014-07-29 | 2019-05-28 | Shenzhen Hightide Biopharmaceutical, Ltd. | Berberine salts, ursodeoxycholic salts and combinations, methods of preparation and application thereof |
| EA032971B1 (en) * | 2014-07-29 | 2019-08-30 | Шэньчжэнь Хайтайд Биофармасьютикал, Лтд. | Berberine and ursodeoxycholic acid salt and application thereof |
| WO2016161921A1 (en) * | 2015-04-06 | 2016-10-13 | Shenzhen Hightide Biopharmaceutical, Ltd. | Conjugate compounds of ursodeoxycholic, berberine or l-carnitine, and compositions and methods thereof |
| CN108137575A (en) * | 2015-04-06 | 2018-06-08 | 深圳君圣泰生物技术有限公司 | Ursodesoxycholic acid and jamaicin or the conjugated compound and its composition and its method of l-cn |
| CN104860940B (en) * | 2015-05-22 | 2017-05-10 | 湖南省中医药研究院中药研究所 | Valproate and protoberberine compounds, preparation method and application |
| CN104860940A (en) * | 2015-05-22 | 2015-08-26 | 湖南省中医药研究院中药研究所 | Valproate and protoberberine compounds, preparation method and application |
| EP3456328A4 (en) * | 2016-05-10 | 2020-02-26 | Shenzhen Hightide Biopharmaceutical., Ltd. | Composition, and application and pharmaceutical preparation thereof |
| 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 |
| 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 |
| 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 |
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Application publication date: 20140820 |