CN1393264A - Application of herberine as sensibilizer of insulin - Google Patents
Application of herberine as sensibilizer of insulin Download PDFInfo
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- CN1393264A CN1393264A CN 01121906 CN01121906A CN1393264A CN 1393264 A CN1393264 A CN 1393264A CN 01121906 CN01121906 CN 01121906 CN 01121906 A CN01121906 A CN 01121906A CN 1393264 A CN1393264 A CN 1393264A
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- insulin
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Abstract
A novel application of berberine as the sensibility enhancer of insulin receptor or its related receptor and the composite medicine containing berberine and insulin or others for treating type-II diabetes are disclosed.
Description
This invention relates to the new purposes of the monomer composition berberine of Chinese medicine Rhizoma Coptidis as euglycemic agent, more specifically say and the present invention relates to the euglycemic agent purposes of berberine as type ii diabetes, the pharmaceutical composition that contains berberine and insulin, and the euglycemic agent of berberine and insulin or other type ii diabetes is united the method that is used for blood sugar lowering or treatment diabetes.。
Diabetes are major diseases of harm humans health, and along with The development in society and economy is in rising trend.Diabetes are divided into two kinds: I type and II type.Type i diabetes accounts for 5% of diabetes number, obvious genetic is arranged and early send out tendency, and patient is mainly caused a disease because of the insulin dyspoiesis; Type ii diabetes accounts for 95% of diabetes general patients, for distributing type, sickness rate was directly proportional with the age, the insulin that normal level is arranged in the patient body, the function that β-islet cells generates insulin is also normal usually, the reason of morbidity mainly is that Insulin receptor INSR or the function of receptors relevant with insulin action are low, causes the insulin resistant state.Patient for type ii diabetes, improve the expression of Insulin receptor INSR and associated receptor, to help insulin (endogenous and external source) to play a role, thereby produce the effect that reduces patient's blood glucose, therefore also be the important target spot that people seek treatment type ii diabetes medicine.
Berberine is a kind of known antibacterials commonly used, and its maximum characteristics are that side effect is extremely rare, is mainly used in treatment bacillary dysentery and enteritis clinically.The berberine molecular weight is 408, and molecular formula is C
20H
16ClNO
42H
2O, its molecular structure is formula as follows.Berberine is a yellow crystalline powder on physicochemical character, and nothing is smelt, and flavor is extremely bitter.
The objective of the invention is to seek the medicine of new Insulin receptor INSR sensitizer and treatment diabetes.
The inventor has now found that after deliberation berberine can and significantly improve insulin receptor gene and peroxisome multiplicaiton factor activated receptor (PPARr) expression of gene with the Insulin receptor INSR interaction, thereby can be the euglycemic agent of type ii diabetes, and can be separately or unite with insulin or other type ii diabetes therapeutic agent and to be used for the treatment of type ii diabetes, the present invention is based on above-mentioned discovery and now finish.
Therefore, first aspect present invention relates to the purposes of berberine as the Insulin receptor INSR sensitizer of type ii diabetes.
The present invention relates to berberine on the other hand and is preparing as the purposes in the Insulin receptor INSR sensitizer of type ii diabetes.
Further aspect of the present invention relates to the pharmaceutical composition that is used for the treatment of type ii diabetes, and it comprises berberine, the medicine of insulin or known treatment type ii diabetes, and/or pharmaceutical carrier or excipient.
Further aspect of the present invention relates to the medicine box that is used for the treatment of type ii diabetes, the other medicines that it comprises berberine and insulin or becomes known for treating type ii diabetes.
The drug combination that further aspect of the present invention relates to berberine and insulin or known treatment type ii diabetes is used for preparing the medicine purposes that is used for the treatment of type ii diabetes.
Further aspect of the present invention relates to the method for the treatment of type ii diabetes, and it comprises that drug administration with berberine and insulin or known treatment type ii diabetes is in the type ii diabetes patient.
According to the present invention, used term " insulin " refers to natural insulin among the present invention, the insulin that chemosynthesis or genetic engineering obtain.Insulin among the present invention is to use as forms such as oral formulations with injection or other possible dosage form.
According to the present invention, used term among the present invention " medicine of known treatment type ii diabetes " refers to the medicine of available from the market treatment type ii diabetes, as with sulphanylureas or make the treatment type ii diabetes medicine of active component with Thiazolidine (as pioglitazone, rosiglitazone etc.).
According to the present invention, when berberine and insulin or the use of known treatment type ii diabetes drug combination, demonstrate good synergism, thereby insulin or known treatment type ii diabetes amount of drug are obviously reduced, toxic and side effects or administration are uncomfortable significantly to be reduced.
According to the present invention, preferably berberine and insulin combination are used for the treatment of type ii diabetes.Berberine and insulin combination order of administration can be simultaneously, or insulin pro-berberine after, or berberine proinsulin after.
Following experiment is implemented to be used for then the present invention is further elaborated or illustrates that it does not mean that the present invention only limits to this.One. the influence that berberine is expressed insulin receptor gene
With 24 hours human lymphocyte (5 * 10 of berberine (10 μ g/ml) processing
6/ ml), extract RNA with the Trizol medicine box, and remove the DNA that pollutes with dnase digestion.The used primer of RT-PCR is following sequence: Insulin receptor INSR 5 '-CCGAAGATTTCCGAGACCTCAG-3 '
5’-CAAACTGCCCGTTGATGACG-3’
RNA is under 30 minutes 60 ℃ of conditions, because the effect of reverse transcription is transcribed into cDNA, through 25 PCR circulations (circulation of PCR variations in temperature), amplifies insulin receptor gene cDNA again, checks its product with 2% agar electrophoresis.And with isotope (
32P) the cDNA band transferred on the film after to electrophoresis of Biao Zhi molecular probe carries out molecular hybridization, and the sequence of molecular probe is as follows:
32P-(5’-ACACGATGTTATTATCCTCCACG-3’)
Twice 42 ℃ 15 minutes wash film after, carry out autoradiography, determine tested expression of gene intensity with Kodak X-O mat.Above-mentioned experiment repeats 5 times, the results are shown in Table 1.
Table 1. berberine is in the external receptor experiment 1 relevant with insulin effector expression intensity * to the influence of insulin receptor gene and PPARr gene expression
Matched group (n=5) berberine group (n=5) Insulin receptor INSR 100 165 ± 10 PPAR-r 100 126 ± 7n=experiment number *: P＜0.01
Above-mentioned molecular biology experiment and table 1 data show that berberine can significantly increase the expression of insulin receptor gene in human lymphocyte is cultivated, and can increase peroxisome multiplicaiton factor activated receptor (PPARr) expression of gene simultaneously.Wherein, there is cell surface in Insulin receptor INSR, insulin have only with its receptors bind after in could active cell signal path and play a role; And PPARr is " orphan receptor " in the nucleus, is the bonded target spot of known euglycemic agent rosiglitazone.Two. the synergism of berberine and insulin coupling
22 volunteers that suffer from type ii diabetes are divided into two groups, and one group is 13 trouble type ii diabetes volunteers, gives insulin for each person every day at twice, dosage 28u/ days; Another group is 9 volunteers that suffer from type ii diabetes, and three berberines of orally give 0.5g/ time, only gave insulin one time, dosage 6u/ days in one day simultaneously for each person every day.Measure respectively above-mentioned experimenter before administration and administration after blood glucose value before the meal, the results are shown in Table 2.
The synergism of table 2. berberine and insulin coupling
Dosage regimen patient's number is blood sugar concentration (mmol/L) before the meal
After the preceding administration of administration
Insulin 28u/ days, twice-daily 13 11.8 ± 3.2 7.7 ± 1.5
Insulin 6u/ days, one day 9 12.1 ± 1.9 6.1 ± 1 berberines (oral, three times on the one, 0.5 gram is once)
Normal value (-) 7.0
Can see by data in the table 2, berberine is used for the treatment of type ii diabetes with insulin combination to be compared with independent insulinize type ii diabetes, and the coupling of berberine and insulin reduces the consumption of insulin to have shown simultaneously and the identical or better hypoglycemic effect of independent use insulin greatly.Therefore berberine and insulin coupling have synergism in the treatment type ii diabetes.
Claims (6)
1. berberine is as the purposes of the Insulin receptor INSR sensitizer of type ii diabetes.
2. berberine is preparing as the purposes in the Insulin receptor INSR sensitizer of type ii diabetes.
3. be used for the treatment of the pharmaceutical composition of type ii diabetes, it comprises berberine, the medicine of insulin or known treatment type ii diabetes, and/or pharmaceutical carrier or excipient.
4. the medicine box that is used for the treatment of type ii diabetes, it comprises the other medicines of berberine and insulin or known treatment type ii diabetes.
5. the drug combination of berberine and insulin or known treatment type ii diabetes is used for preparing the medicine purposes that is used for the treatment of type ii diabetes.
6. the method for treatment type ii diabetes, it comprises that drug administration with berberine and insulin or known treatment type ii diabetes is in the type ii diabetes patient.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 01121906 CN1393264A (en) | 2001-06-22 | 2001-06-22 | Application of herberine as sensibilizer of insulin |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 01121906 CN1393264A (en) | 2001-06-22 | 2001-06-22 | Application of herberine as sensibilizer of insulin |
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| Publication Number | Publication Date |
|---|---|
| CN1393264A true CN1393264A (en) | 2003-01-29 |
Family
ID=4664596
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 01121906 Pending CN1393264A (en) | 2001-06-22 | 2001-06-22 | Application of herberine as sensibilizer of insulin |
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008040192A1 (en) * | 2006-09-30 | 2008-04-10 | Shanghai Institute Of Materia Medica, Chinese Academy Of Sciences | 13,13a-DIHYDROBERBERINE DERIVATIVES, THEIR PHARMACEUTICAL COMPOSITION AND USE |
| CN101816653A (en) * | 2010-04-29 | 2010-09-01 | 苏州基莫夫药物开发有限公司 | Application of berberine in preparing tumor radio sensitization medicine |
| CN101874833A (en) * | 2009-04-30 | 2010-11-03 | 成都中医药大学 | Novel application of wine-roasted Chinese goldthread processed product |
| CN101874831A (en) * | 2009-04-30 | 2010-11-03 | 成都中医药大学 | New application of coptis product processed by ginger juice |
| CN101874830A (en) * | 2009-04-30 | 2010-11-03 | 成都中医药大学 | New application of golden thread processed product |
| EP2217067A4 (en) * | 2007-11-07 | 2011-01-19 | Burnham Inst Medical Research | Method and compounds for modulating insulin production |
-
2001
- 2001-06-22 CN CN 01121906 patent/CN1393264A/en active Pending
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008040192A1 (en) * | 2006-09-30 | 2008-04-10 | Shanghai Institute Of Materia Medica, Chinese Academy Of Sciences | 13,13a-DIHYDROBERBERINE DERIVATIVES, THEIR PHARMACEUTICAL COMPOSITION AND USE |
| EP2217067A4 (en) * | 2007-11-07 | 2011-01-19 | Burnham Inst Medical Research | Method and compounds for modulating insulin production |
| US8168391B2 (en) | 2007-11-07 | 2012-05-01 | Burnham Institute For Medical Research | Method for modulating insulin production |
| CN101874833A (en) * | 2009-04-30 | 2010-11-03 | 成都中医药大学 | Novel application of wine-roasted Chinese goldthread processed product |
| CN101874831A (en) * | 2009-04-30 | 2010-11-03 | 成都中医药大学 | New application of coptis product processed by ginger juice |
| CN101874834A (en) * | 2009-04-30 | 2010-11-03 | 成都中医药大学 | New application of processed products of Chinese goldthread stir-fried with rice vinegar |
| CN101874830A (en) * | 2009-04-30 | 2010-11-03 | 成都中医药大学 | New application of golden thread processed product |
| CN101874830B (en) * | 2009-04-30 | 2015-05-20 | 成都中医药大学 | New application of golden thread processed product |
| CN101816653A (en) * | 2010-04-29 | 2010-09-01 | 苏州基莫夫药物开发有限公司 | Application of berberine in preparing tumor radio sensitization medicine |
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| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
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