WO2004032924A1 - Emploi de berberine en tant que sensibilisant insulinique - Google Patents

Emploi de berberine en tant que sensibilisant insulinique Download PDF

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Publication number
WO2004032924A1
WO2004032924A1 PCT/CN2002/000715 CN0200715W WO2004032924A1 WO 2004032924 A1 WO2004032924 A1 WO 2004032924A1 CN 0200715 W CN0200715 W CN 0200715W WO 2004032924 A1 WO2004032924 A1 WO 2004032924A1
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WO
WIPO (PCT)
Prior art keywords
insulin
diabetes
type
berberine
receptor
Prior art date
Application number
PCT/CN2002/000715
Other languages
English (en)
Chinese (zh)
Inventor
Jiandong Jiang
Jing Wei
Zizheng Wang
Huaining Pan
Original Assignee
Jiandong Jiang
Jing Wei
Zizheng Wang
Huaining Pan
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Jiandong Jiang, Jing Wei, Zizheng Wang, Huaining Pan filed Critical Jiandong Jiang
Priority to AU2002335304A priority Critical patent/AU2002335304A1/en
Priority to PCT/CN2002/000715 priority patent/WO2004032924A1/fr
Publication of WO2004032924A1 publication Critical patent/WO2004032924A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/4375—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics

Definitions

  • This invention relates to the new use of berberine, a monomer component of the Chinese medicine Coptis chinensis, as an insulin sensitizer. More specifically, this invention relates to the use of berberine as an insulin sensitizer for type II diabetes. In combination with berberine and insulin or other insulin sensitizers for type II diabetes, a method for lowering blood sugar or treating diabetes.
  • Type I diabetes accounts for 5% of the diabetic population, with obvious heredity and early onset. Patients are mainly caused by impaired insulin production; Type II diabetes accounts for 95% of total diabetes patients, which is sporadic and the incidence is directly proportional to age Patients have normal levels of insulin, and the function of ⁇ -islet cells to produce insulin is also normal. The main cause of the disease is the low function of insulin receptors or insulin-related receptors, which leads to insulin resistance.
  • insulin receptors and related receptors will help insulin (endogenous and exogenous) to function, which will have the effect of lowering blood sugar in patients, so people are looking for treatment of type II An important rake point for diabetes drugs.
  • Berberine is a commonly known antibacterial drug. Its biggest feature is that side effects are extremely rare. It is mainly used in clinical treatment of bacterial dysentery and enteritis. Berberin has a molecular weight of 408 and a molecular formula of C 2 () H 16 C1N0 4 ⁇ 2 ⁇ 2 0. Its molecular structure is shown in the following formula. In physical and chemical properties, berberine is a yellow crystalline powder, odorless and extremely bitter.
  • the object of the present invention is to find new insulin receptor sensitizers and drugs for treating diabetes.
  • the inventors have discovered through research that berberine can interact with the insulin receptor and significantly increase the expression of the insulin receptor gene and the peroxisome proliferator-activated receptor (PPARr) gene, so that it can be an insulin increase for type II diabetes Sensitizer, and can be used alone or in combination with insulin or other type II diabetes treatment agents to treat type II diabetes, the present invention has been completed based on the above findings.
  • PPARr peroxisome proliferator-activated receptor
  • the first aspect of the present invention relates to the use of berberine as an insulin receptor sensitizer for type II diabetes.
  • Another aspect of the invention relates to the use of berberine in the preparation of an insulin receptor sensitizer for type II diabetes.
  • a further aspect of the invention relates to a pharmaceutical composition for treating type II diabetes, which comprises berberine, insulin or a drug known to treat type II diabetes, and / or a pharmaceutically acceptable carrier or excipient.
  • Yet another aspect of the invention relates to a kit for treating type II diabetes mellitus, which comprises berberin and insulin or other drugs known for treating type II diabetes.
  • a further aspect of the invention relates to the use of berberine in combination with insulin or a drug known to treat type II diabetes for the manufacture of a medicament for treating type II diabetes.
  • Yet another aspect of the present invention relates to a method of treating type II diabetes, which comprises administering berberine and insulin or a drug known to treat type II diabetes to a patient with type II diabetes.
  • a method of treating type II diabetes which comprises administering berberine and insulin or a drug known to treat type II diabetes to a patient with type II diabetes.
  • insulin refers to natural insulin, chemically synthesized or genetically engineered insulin.
  • the insulin in the present invention is used in the form of an injection or possibly other dosage forms such as an oral preparation.
  • the term "medicine known to treat type II diabetes” as used in the present invention refers to a commercially available drug for treating type II diabetes, such as sulfonylureas or thiazole (Such as pioglitazone, rosiglitazone, etc.) as active ingredients in the treatment of type II diabetes.
  • a commercially available drug for treating type II diabetes such as sulfonylureas or thiazole (Such as pioglitazone, rosiglitazone, etc.) as active ingredients in the treatment of type II diabetes.
  • berberine when berberine is used in combination with insulin or a known drug for the treatment of type II diabetes, it shows an excellent synergistic effect, so that the dosage of insulin or a known drug for the treatment of type II diabetes is significantly reduced, toxic side effects or administration Discomfort was significantly reduced.
  • berberine is preferably used in combination with insulin for the treatment of type II diabetes.
  • the order of co-administration of berberine and insulin can be simultaneous, or insulin preceded by berberine, or berberine preceded by insulin.
  • Insulin receptor 5 5-CCGAAGATTTCCGAGACCTCAG-3,
  • RNA was transcribed into cDNA at 60 ° C for 30 minutes due to the action of reverse transcriptase.
  • the insulin receptor gene cDNA was amplified and examined by 2% agar electrophoresis.
  • the product was hybridized with a molecular probe labeled with an isotope ( 32 P) to the cDNA band transferred to the membrane after electrophoresis, and the sequence of the molecular probe was as follows:
  • berberine can significantly increase the expression of insulin receptor genes in human lymphocyte culture, and can simultaneously increase the peroxisome proliferator-activated receptor (PPARr ) Gene expression.
  • PPARr peroxisome proliferator-activated receptor
  • the insulin receptor exists on the cell surface, and insulin can activate the intracellular signaling pathway only after binding to its receptor;
  • PPARr is an orphan receptor in the nucleus, which is a known insulin sensitizer rosiglitazone binding Point.
  • Twenty-two volunteers with type II diabetes were divided into two groups. One group was 13 volunteers with type II diabetes. Each person was given insulin twice daily at a dose of 28u / day. The other group was 9 Volunteers with type II diabetes were orally administered berberine three times a day, 0.5 g / time, while insulin was given only once a day, at a dose of 6u / day. The pre-meal and pre-meal blood glucose values of the above subjects were measured, and the results are shown in Table 2. Table 2. Synergistic effect of berberine combined with insulin. Dosage plan. Number of patients before meals. Blood glucose concentration before meals (mmol / L). Insulin 28u / day after dosing before administration. . 7 soil 1. 5 insulin 6u / day, once a day 9 12. 1 ⁇ 1. 9 6. 1 ⁇ 1 Berberine (oral, three times a day, 0.5 grams once)

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  • Health & Medical Sciences (AREA)
  • Diabetes (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Obesity (AREA)
  • Hematology (AREA)
  • Engineering & Computer Science (AREA)
  • Endocrinology (AREA)
  • Emergency Medicine (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne une composition contenant de la berbérine avec de l'insuline ou d'autres médicaments connus pouvant être utilisée dans le cas du diabète DNID, ainsi que l'emploi de berbérine en tant que récepteur insulinique ou sensibilisant insulinique.
PCT/CN2002/000715 2002-10-10 2002-10-10 Emploi de berberine en tant que sensibilisant insulinique WO2004032924A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
AU2002335304A AU2002335304A1 (en) 2002-10-10 2002-10-10 The use of berberine as insulin sensitizer
PCT/CN2002/000715 WO2004032924A1 (fr) 2002-10-10 2002-10-10 Emploi de berberine en tant que sensibilisant insulinique

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/CN2002/000715 WO2004032924A1 (fr) 2002-10-10 2002-10-10 Emploi de berberine en tant que sensibilisant insulinique

Publications (1)

Publication Number Publication Date
WO2004032924A1 true WO2004032924A1 (fr) 2004-04-22

Family

ID=32075156

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2002/000715 WO2004032924A1 (fr) 2002-10-10 2002-10-10 Emploi de berberine en tant que sensibilisant insulinique

Country Status (2)

Country Link
AU (1) AU2002335304A1 (fr)
WO (1) WO2004032924A1 (fr)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101816653A (zh) * 2010-04-29 2010-09-01 苏州基莫夫药物开发有限公司 黄连素作为制备肿瘤放射治疗增敏药物中的应用
EP2217067A4 (fr) * 2007-11-07 2011-01-19 Burnham Inst Medical Research Procédé et composés pour la régulation de la production d'insuline
US20110165273A1 (en) * 2008-09-05 2011-07-07 Jiao Guo A composition of extracts from plants and the use thereof in prophylaxis or treatment of metabolism disorder of blood lipid
EP2405755A1 (fr) * 2009-03-11 2012-01-18 Xintria Pharmaceutical Corporation, Inc. Méthodes et compositions utilisées pour le traitement de maladies métaboliques et cardiovasculaires
US20140364363A1 (en) * 2011-12-30 2014-12-11 Joslin Diabetes Center, Inc. Glypican-4 based compositions and methods for treating and diagnosing insulin resistance

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108245551A (zh) * 2017-11-07 2018-07-06 南方医科大学 一种防治胰岛素抵抗相关疾病的药物组合物及其制备方法

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
CHEN HAIFEI ET AL.: "44 cases of clinic observing for using berberine to treat senile NIDDM", JIANG XI ZHONG YI YAO, vol. 30, no. 1, 1999 *
YUAN YUHONG: "clinic observing for using berbering to treat NIDDM", XIAN DAI ZHONG XI YI JIE HA ZA ZHI, vol. 8, no. 11, 1999, pages 1777 *

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2217067A4 (fr) * 2007-11-07 2011-01-19 Burnham Inst Medical Research Procédé et composés pour la régulation de la production d'insuline
US8168391B2 (en) 2007-11-07 2012-05-01 Burnham Institute For Medical Research Method for modulating insulin production
US20110165273A1 (en) * 2008-09-05 2011-07-07 Jiao Guo A composition of extracts from plants and the use thereof in prophylaxis or treatment of metabolism disorder of blood lipid
US8394431B2 (en) * 2008-09-05 2013-03-12 Jiao Guo Composition of extracts from plants and the use thereof in prophylaxis or treatment of metabolism disorder of blood lipid
EP2405755A1 (fr) * 2009-03-11 2012-01-18 Xintria Pharmaceutical Corporation, Inc. Méthodes et compositions utilisées pour le traitement de maladies métaboliques et cardiovasculaires
EP2405755A4 (fr) * 2009-03-11 2012-11-28 Xintria Pharmaceutical Corp Inc Méthodes et compositions utilisées pour le traitement de maladies métaboliques et cardiovasculaires
CN101816653A (zh) * 2010-04-29 2010-09-01 苏州基莫夫药物开发有限公司 黄连素作为制备肿瘤放射治疗增敏药物中的应用
US20140364363A1 (en) * 2011-12-30 2014-12-11 Joslin Diabetes Center, Inc. Glypican-4 based compositions and methods for treating and diagnosing insulin resistance
US9446096B2 (en) * 2011-12-30 2016-09-20 Joslin Diabetes Center, Inc. Glypican-4 based compositions and methods for treating and diagnosing insulin resistance

Also Published As

Publication number Publication date
AU2002335304A1 (en) 2004-05-04

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