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
- diabetes
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- berberine
- treatment
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- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 title claims abstract description 82
- 102000004877 Insulin Human genes 0.000 title claims abstract description 41
- 108090001061 Insulin Proteins 0.000 title claims abstract description 41
- 229940125396 insulin Drugs 0.000 title claims abstract description 41
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims abstract description 43
- YBHILYKTIRIUTE-UHFFFAOYSA-N berberine Chemical compound C1=C2CC[N+]3=CC4=C(OC)C(OC)=CC=C4C=C3C2=CC2=C1OCO2 YBHILYKTIRIUTE-UHFFFAOYSA-N 0.000 claims abstract description 37
- 229940093265 berberine Drugs 0.000 claims abstract description 37
- QISXPYZVZJBNDM-UHFFFAOYSA-N berberine Natural products COc1ccc2C=C3N(Cc2c1OC)C=Cc4cc5OCOc5cc34 QISXPYZVZJBNDM-UHFFFAOYSA-N 0.000 claims abstract description 37
- 239000003814 drug Substances 0.000 claims abstract description 18
- 101000852815 Homo sapiens Insulin receptor Proteins 0.000 claims description 11
- 102100036721 Insulin receptor Human genes 0.000 claims description 11
- 229940079593 drug Drugs 0.000 claims description 3
- 239000000890 drug combination Substances 0.000 claims description 3
- 238000000034 method Methods 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 238000001647 drug administration Methods 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 102000005962 receptors Human genes 0.000 abstract description 7
- 108020003175 receptors Proteins 0.000 abstract description 7
- 108010001127 Insulin Receptor Proteins 0.000 abstract description 6
- 102000003746 Insulin Receptor Human genes 0.000 abstract 1
- 239000002131 composite material Substances 0.000 abstract 1
- 239000003623 enhancer Substances 0.000 abstract 1
- 230000014509 gene expression Effects 0.000 description 7
- 239000003795 chemical substances by application Substances 0.000 description 6
- 206010012601 diabetes mellitus Diseases 0.000 description 6
- 230000001610 euglycemic effect Effects 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 5
- YASAKCUCGLMORW-UHFFFAOYSA-N Rosiglitazone Chemical compound C=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O YASAKCUCGLMORW-UHFFFAOYSA-N 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 230000008878 coupling Effects 0.000 description 4
- 238000010168 coupling process Methods 0.000 description 4
- 238000005859 coupling reaction Methods 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 150000003836 berberines Chemical group 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 239000002299 complementary DNA Substances 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- 230000004087 circulation Effects 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 238000001962 electrophoresis Methods 0.000 description 2
- 230000003203 everyday effect Effects 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 210000004698 lymphocyte Anatomy 0.000 description 2
- 235000012054 meals Nutrition 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000003068 molecular probe Substances 0.000 description 2
- 210000002824 peroxisome Anatomy 0.000 description 2
- HYAFETHFCAUJAY-UHFFFAOYSA-N pioglitazone Chemical compound N1=CC(CC)=CC=C1CCOC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 HYAFETHFCAUJAY-UHFFFAOYSA-N 0.000 description 2
- 229960004586 rosiglitazone Drugs 0.000 description 2
- OGYGFUAIIOPWQD-UHFFFAOYSA-N 1,3-thiazolidine Chemical compound C1CSCN1 OGYGFUAIIOPWQD-UHFFFAOYSA-N 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 208000004429 Bacillary Dysentery Diseases 0.000 description 1
- 208000004232 Enteritis Diseases 0.000 description 1
- 206010017915 Gastroenteritis shigella Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 102000016978 Orphan receptors Human genes 0.000 description 1
- 108070000031 Orphan receptors Proteins 0.000 description 1
- 108010076181 Proinsulin Proteins 0.000 description 1
- 241001062472 Stokellia anisodon Species 0.000 description 1
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 238000000376 autoradiography Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 238000009396 hybridization Methods 0.000 description 1
- 230000002218 hypoglycaemic effect Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 206010025482 malaise Diseases 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 229960005095 pioglitazone Drugs 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 238000010839 reverse transcription Methods 0.000 description 1
- 238000003757 reverse transcription PCR Methods 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 201000005113 shigellosis Diseases 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
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 |
Publications (1)
| 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 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1393264A (en) |
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 |
| CN101874831A (en) * | 2009-04-30 | 2010-11-03 | 成都中医药大学 | New application of processed products of Ginger and Coptis chinensis |
| CN101874833A (en) * | 2009-04-30 | 2010-11-03 | 成都中医药大学 | The New Application of the Processed Products of Coptidis Coptidis Rooted in Wine |
| CN101874830A (en) * | 2009-04-30 | 2010-11-03 | 成都中医药大学 | New Application of Processed Coptidis Rhizome of Cornus officinalis |
| EP2217067A4 (en) * | 2007-11-07 | 2011-01-19 | Burnham Inst Medical Research | METHOD AND COMPOUNDS FOR REGULATING 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 REGULATING INSULIN PRODUCTION |
| US8168391B2 (en) | 2007-11-07 | 2012-05-01 | Burnham Institute For Medical Research | Method for modulating insulin production |
| CN101874831A (en) * | 2009-04-30 | 2010-11-03 | 成都中医药大学 | New application of processed products of Ginger and Coptis chinensis |
| CN101874834A (en) * | 2009-04-30 | 2010-11-03 | 成都中医药大学 | New application of processed products of Coptis chinensis broiled in vinegar |
| CN101874833A (en) * | 2009-04-30 | 2010-11-03 | 成都中医药大学 | The New Application of the Processed Products of Coptidis Coptidis Rooted in Wine |
| CN101874830A (en) * | 2009-04-30 | 2010-11-03 | 成都中医药大学 | New Application of Processed Coptidis Rhizome of Cornus officinalis |
| 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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