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WO2008156331A2 - Nouvelle utilisation de composés de lignane - Google Patents

Nouvelle utilisation de composés de lignane Download PDF

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Publication number
WO2008156331A2
WO2008156331A2 PCT/KR2008/003525 KR2008003525W WO2008156331A2 WO 2008156331 A2 WO2008156331 A2 WO 2008156331A2 KR 2008003525 W KR2008003525 W KR 2008003525W WO 2008156331 A2 WO2008156331 A2 WO 2008156331A2
Authority
WO
WIPO (PCT)
Prior art keywords
formula
compound represented
diabetes
preventing
treating
Prior art date
Legal status (The legal status 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 status listed.)
Ceased
Application number
PCT/KR2008/003525
Other languages
English (en)
Other versions
WO2008156331A3 (fr
Inventor
Jae-Kwan Hwang
Jae Young Lee
Jeong Hwan Kim
Jae-Seok Shim
Hae Ji Lee
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Biocare Co Ltd
Original Assignee
Biocare Co Ltd
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
Priority claimed from KR1020080019147A external-priority patent/KR100959557B1/ko
Application filed by Biocare Co Ltd filed Critical Biocare Co Ltd
Publication of WO2008156331A2 publication Critical patent/WO2008156331A2/fr
Publication of WO2008156331A3 publication Critical patent/WO2008156331A3/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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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
    • A61K31/075—Ethers or acetals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • 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
    • A61P3/04—Anorexiants; Antiobesity agents

Definitions

  • the present invention relates to novel use of lignan compounds, and more particularly, the present invention relates to novel use of an extract of the aril of nutmeg, 2- (4-allyl-2 , 6-dimethoxyphenoxy) -1- (4-hydroxy-
  • PPAR peroxisome proliferator activated receptor
  • peroxisome proliferator activated receptor is nuclear receptor which bind with the compound increasing number of peroxisome, named as peroxisome proliferator as a ligand, and PPAR ⁇ , PPAR ⁇ , isoform of PPARyhas been known (J. Steroid Biochem. Molec. Biol., 51, 157, 1994; Gene Expression, 4, 281, 1995; Biochem. Biophys. Res. Commun . , 224, 431, 1996).
  • PPAR mainly regulates expression of genes which are related to lipid metabolism or differentiation of adipocyte (J “ . Invest. Dermatol. Ill, 1116-1121, 1998; J “ . Med. Chem. , 43, 527-550, 2000), and PPAR ⁇ which is an isoform of PPAR mainly expressed in liver, retina, adipose tissue, and related to oxidation of fatty acid or neutralization of toxic materials, and inflammation.
  • PPAR ⁇ is not expressed in the manner of tissue-specific, rather it is expressed broadly and its function is not identified. (Endocrinology., 137, 354, 1996).
  • the diabetes may be classified into type 1 and type 2.
  • the type 1 diabetes is autoimmune disease which pancreas induce immunological reaction by genetic susceptibility and viral infaction, and ⁇ -cells are selectively destroyed.
  • the type 2 diabetes is the type which insulin resistance is priory occurred and reported that caused by complicated factors such as obesity, reduction of insulin receptor, reduction of tyrosine kinase activity, reduction of muscle/adipose tissue type transporter in muscle and fat tissues, deficiency of insulin receptor substrate-1 (IRS-I) in the cells.
  • the type 2 diabetes is mainly occurred in adult and it occupies 90% of diabetes (Drugs, 65: 433-445, 2005).
  • the present invention provides method comprising administering an effective amount of C1-C6 organic solvent extract of the aril of nutmeg to a subject in need thereof.
  • the present invention provides a method comprising administering an effective amount of one which is selected from the group consisting of a compound represented by Formula 1, a compound represented by Formula 2, and a compound represented by Formula 3, or their pharmaceutically acceptable salts for preventing or treating diabetes.
  • the present invention provides a method comprising administering an effective amount of one which is selected from the group consisting of a compound represented by Formula 1, a compound represented by Formula 2 , and a compound represented by Formula 3 , or their pharmaceutically acceptable salts for preventing or treating PPARY mediated diseases.
  • various solvents including purified water, methanol, ethanol , propanol , isopropanol, butanol, acetone, ether, benzene, chloroform, ethyl acetate, methylene chloride, hexane, cyclohexane, petroleum ether and the like, may be used alone or in a mixture thereof.
  • the extract obtained as described above is subjected to silica gel column chromatography to obtain fractions according to polarity, and the separated specific fraction is subjected to reverse phase column chromatography and high-performance liquid chromatography (HPLC), thus separating 2- (4-allyl-2 , 6-dimethoxyphenoxy) - 1- (4-hydroxy-3-methoxyphenyl) -propane, austrobailignan-7 and licarin E from the fraction.
  • HPLC high-performance liquid chromatography
  • the method for extracting and separating the active ingredients is not necessarily limited to the above-described method.
  • a known method for finding a ligand, which activates a gene having a PPAR response element (PPRE) , by binding to PPAR ⁇ was used to confirm that the inventive 2- (4-allyl- 2, 6-dimethoxyphenoxy) -1- (4-hydroxy-3-methoxyphenyl) - propane, austrobailignan-7 and licarin E bind to PPAR, particularly PPAR ⁇ , to activate PPAR (FIGS. 12 and 20) .
  • mice continually ingest excessive food because their appetite is not regulated due to the deletion of a leptin gene. As a result, fat is excessively accumulated in the body, and at about 3 months after birth, the mice maintain a weight of about
  • mice become type 2 diabetic models having a blood glucose level higher than that of wild-type mice
  • this invention provides a use of C1-C6 organic solvent extracts of the aril of nutmug for preparing diabetes treating reagent.
  • the method of extraction and isolation for preparing extracts of the aril of nut is well described above, and it may be used to those skilled in the art according method which is well known in the art for preparing diabetes treating reagent .
  • 2- (4-allyl-2 , 6- dimethoxyphenoxy) -1- (4-hydroxy-3 -methoxyphenyl) -propane and austrobailignan-7 increased PPARy activity in a concentration-dependent manner and showed a significant difference (**, p ⁇ 0.01) from the control group at all the treatment concentrations.
  • RNA of the cells was isolated using TRIZOL (Invitrogen, USA) .
  • the isolated total RNA was quantified, and then the RNA in the same amount for each sample was synthesized into cDNA at 42 ° C for 20 minutes using reverse transcriptase.

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  • Health & Medical Sciences (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Botany (AREA)
  • Mycology (AREA)
  • Microbiology (AREA)
  • Medical Informatics (AREA)
  • Biotechnology (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Hematology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Diabetes (AREA)
  • Child & Adolescent Psychology (AREA)
  • Obesity (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

Cette invention concerne une nouvelle utilisation de composés de lignane, plus particulièrement, une nouvelle utilisation d'un extrait d'arille de muscade, 2- (4-allyl-2, 6-dimethoxyphenoxy) -1- (4-hydroxy- 3 -methoxyphenyl) -propane, l'austrobailignane 7 ou la licarine E, pour prévenir ou traiter le diabète ou des maladies induites par PPARγ. Le composé susmentionné et l'extrait d'arille de muscade agissent en tant que ligands pour PPARγ, et ils peuvent être utilisés pour prévenir ou traiter des maladies induites par PPARγ parmi lesquelles, entre autres, le diabète et une complication diabétique. Ainsi, 2- (4-allyl-2, 6- dimethoxyphenoxy) -1- (4 -hydroxy-3 -methoxyphenyl) -propane, l'austrobailignane 7 ou la licarine E et l'extrait d'arille de muscade peuvent être utiles en tant qu'agent prophylactique ou thérapeutique pour des maladies induites par PPARγ, parmi lesquelles, entre autres, le diabète et une complication diabétique.
PCT/KR2008/003525 2007-06-20 2008-06-20 Nouvelle utilisation de composés de lignane Ceased WO2008156331A2 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
KR20070060176 2007-06-20
KR10-2007-0060176 2007-06-20
KR10-2008-0019147 2008-02-29
KR1020080019147A KR100959557B1 (ko) 2007-06-20 2008-02-29 육두구 가종피 추출 화합물을 유효성분으로 포함하는당뇨병 또는 피피에이알-감마 매개 질환 예방 및 치료용약학적 조성물

Publications (2)

Publication Number Publication Date
WO2008156331A2 true WO2008156331A2 (fr) 2008-12-24
WO2008156331A3 WO2008156331A3 (fr) 2009-02-26

Family

ID=40156812

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/KR2008/003525 Ceased WO2008156331A2 (fr) 2007-06-20 2008-06-20 Nouvelle utilisation de composés de lignane

Country Status (1)

Country Link
WO (1) WO2008156331A2 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2438923A4 (fr) * 2009-06-01 2012-11-28 Univ Chosun Iacf Composition, pour la prévention ou le traitement d'affections liées à l'obésité et médiées par l'activation d'ampk, et dont les principes actifs dont des lignanes de 2,5-bis-aryl-3,4-diméthyltétrahydrofurane
CN113440517A (zh) * 2021-06-07 2021-09-28 江南大学 利卡灵b在制备预防或/和治疗非酒精性脂肪肝病药物中的应用

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2006273788A (ja) * 2005-03-30 2006-10-12 Kaneka Corp Ｐｐａｒリガンド活性を有する植物由来の組成物
KR100830192B1 (ko) * 2005-09-22 2008-05-19 (주)바이오케어 메이스리그난 또는 이의 약제학적으로 허용 가능한 염을유효성분으로 함유하는 ＰＰＡＲα에 의해 매개되는 질환의예방 또는 치료용 조성물

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2438923A4 (fr) * 2009-06-01 2012-11-28 Univ Chosun Iacf Composition, pour la prévention ou le traitement d'affections liées à l'obésité et médiées par l'activation d'ampk, et dont les principes actifs dont des lignanes de 2,5-bis-aryl-3,4-diméthyltétrahydrofurane
CN103936698A (zh) * 2009-06-01 2014-07-23 朝鲜大学校产学协力团 用于预防或治疗肥胖或代谢综合征的组合物
CN113440517A (zh) * 2021-06-07 2021-09-28 江南大学 利卡灵b在制备预防或/和治疗非酒精性脂肪肝病药物中的应用

Also Published As

Publication number Publication date
WO2008156331A3 (fr) 2009-02-26

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