WO1998042350A1 - Composition pharmaceutique abaissant le taux de cholesterol - Google Patents

Composition pharmaceutique abaissant le taux de cholesterol Download PDF

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Publication number
WO1998042350A1
WO1998042350A1 PCT/KR1997/000127 KR9700127W WO9842350A1 WO 1998042350 A1 WO1998042350 A1 WO 1998042350A1 KR 9700127 W KR9700127 W KR 9700127W WO 9842350 A1 WO9842350 A1 WO 9842350A1
Authority
WO
WIPO (PCT)
Prior art keywords
cholesterol
compound
pharmaceutical composition
pentagalloylglucose
solution
Prior art date
Application number
PCT/KR1997/000127
Other languages
English (en)
Inventor
Jong Koo Park
Hong Suk Kye
Hi Jae Cho
Chul Hoon Lee
Young Hoon Kim
Jae Kyu Shin
Original Assignee
Cheil Jedang Corporation
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 Cheil Jedang Corporation filed Critical Cheil Jedang Corporation
Priority to AU31923/97A priority Critical patent/AU3192397A/en
Publication of WO1998042350A1 publication Critical patent/WO1998042350A1/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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7024—Esters of saccharides
    • 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)
    • A61K36/65—Paeoniaceae (Peony family), e.g. Chinese peony

Definitions

  • the present invention relates to a novel pharmaceutical composition useful in preventing or treating hypercholesterolemia or atherosclerosis or promoting lipid metabolism in mamr ⁇ als.
  • Cholesterol is a component of animal cell membrane and an important lipid as precusors of bile acid, steroid hormone, vitamin D, etc.
  • Cholesterol level in body is defined as the combination of exogenous cholesterol taken in from outside, endogenous cholesterol biosynthesized in the body, and bile acids discharged into the stool and urine.
  • the ratio of exogenous holesterol to endogenous cholesterol is about 3: 1. That is, the quantity of cholesterol synthesized in the body is even greater than that of cholesterol taken in from outside and much of such endogenous cholesterol is biosynthesized in the liver.
  • the drug for the treatment of hypercholesterolemia or atherosclerosis includes internal uptake inhibitor (Cholestyramin), lipid metabolism promotor (Heparin) and cholesterol biosynthesis inhibitor (Lovastatin).
  • internal uptake inhibitor Choestyramin
  • Heparin lipid metabolism promotor
  • Lovastatin cholesterol biosynthesis inhibitor
  • the 1,2,3,4,6-O-pentagalloylglucose compound of the present invention is isolated from Paeonia m ⁇ irfan SIM., Paeoniaceae.
  • This medicinal plant is known to exhibit pharmacological actions such as antiinflammation, thrombocyte agglutinati, anti hemorrhage, analgesia, antiparalysis, gastric secretion, antibacterial action, etc, but there are no reports suggesting cholesterol lowering action thereof.
  • the present pentagalloylglucose compound can be orally administered, injected or infused in single or, preferably, in combination with conventional pharmaceutically acceptable carriers, adjuvants or additives.
  • the present compound may be formulated into tablet, solution, capsule, granule, particle, powder, injection, etc.
  • the carrier for oral formulation includes, for example, starch, mannitol, crystalline cellulose, CMC Na, water, ethanol, etc.
  • the carrier for injection includes water, physiological saline solution, glucose solution, and other conventionally used solutions.
  • the dry powder of Paeonia woulan SIM. was extracted in 80% methanol solution at the temperature of 70 °C for 3 hours.
  • the methanol was removed from the resulting extracts under reduced pressure and the further extraction was carried out using n-butanol.
  • the resulting extracts was chromatographed on silica gel, eluting with n-hexane and ethanol to yield active fraction which was then run on high performance liquid chromatography column to isolate the 1,2,3,4,6-O-pentagalloylglucose compound (C ) H 32 O 26 , MW 940.70).
  • test compound was added to 0.1 mM potassium phosphate buffer, pH 7.4, comprising rat liver microsome fraction (containing 0.1 mg of proteins), rat liver cytosol fraction (containing 0.1 mg of proteins), 1 mM
  • a control was also prepared and measured with the same manner as described above but not using any test compounds.
  • test compound was added to 0 1 M potassium phosphate buffer, pH 7.4, comprising rat liver microsome fraction (containing 0.05 mg of proteins), 5 mM potassium chloride, 10 mM potassium fluoride, 1 mM
  • NADPH 30 mM nicotinamide, 001 mM tolnaftate and 0.01 mM [1-1H] ammonium farnesylpyrophosphate to prepare 100 ⁇ l of reaction mixture.
  • the reaction mixture was incubated at 37 °C for 2 hours, the reaction was stopped by the addition of 400 ⁇ l of 20% sodium hydroxide (95% ethanol solution).
  • the reaction mixture was saponified at 75 °C for 30 minutes and 200 ⁇ l of distilled water and 500 ⁇ l of petroleum ether were then added to extract the squalene.
  • the extracted squalene was concentrated and dried to obtain a residue.
  • a control was also prepared and measured in the same manner as described above but not using any test compounds.
  • group A was supplied with conventional solid rat feeds for ten days and was orally administered with 0.2% aqueous methylcellulose solution once each day.
  • Group B was supplied with high cholesterol level solid feeds and was orally administered with 0.2% aqueous methylcellulose solution once each day
  • group C was supplied with high cholesterol level solid feeds and orally administered with a solution of pentagalloylglucose compound (100 mg/kg of rat weight/5ml) in 0.2% methylcellulose
  • group D was supplied with high cholesterol level solid feeds and orally administered with a solution of pentagalloylglucose compound (300 mg kg of rat weight/5ml) in 0.2% methylcellulose.
  • day 1 the feeding was stopped and the rats were killed. After bloods were collected from the dead rats and serum was separated, levels of triglyceride (TG), cholesterol (TC) and high density lipoprotein cholesterol (HDL-C) were measured using Blood
  • LDL-C low density lipoprotein cholesterol
  • LDL-C Total TC - (TG/5 + HDL-C)
  • groups A, B and C were supplied with conventional solid rat feeds for ten days. Once each day during that period, group A was orally administered with 0.2% aqueous methylcellulose solution, group B was orally administered with a solution of pentagalloyl glucose compound (30 mg/kg of rat weight 5ml) in 0.2% methylcellulose, and group C was orally administered with a solution of lobastatin (30 mg/kg of rat weight/5ml) in 0.2% methylcellulose. On day 1 1 the feeding was stopped and the rats were killed. After bloods were collected from the dead rats and serum was separated, levels of triglyceride (TG), cholesterol (TC) and high density lipoprotein cholesterol (HDL-C) were measured using
  • LDL-C Total TC - (TG/5 + HDL-C)

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Chemical & Material Sciences (AREA)
  • Molecular Biology (AREA)
  • Engineering & Computer Science (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Biotechnology (AREA)
  • Botany (AREA)
  • Medical Informatics (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
  • Medicines Containing Plant Substances (AREA)
  • Steroid Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention a pour objet une nouvelle composition pharmaceutique servant à prévenir ou à traiter l'hypercholestérolémie ou l'athérosclérose, ou encore à favoriser le métabolisme des lipides chez les mammifères; elle comprend une quantité efficace de 1,2,3,4,5,6-O-pentagalloylglucose ayant la structure: (I).
PCT/KR1997/000127 1997-03-21 1997-06-27 Composition pharmaceutique abaissant le taux de cholesterol WO1998042350A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU31923/97A AU3192397A (en) 1997-03-21 1997-06-27 Cholesterol lowering pharmaceutical composition

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
KR1997/10651 1997-03-21
KR1019970010651A KR19980074710A (ko) 1997-03-21 1997-03-21 콜레스테롤 저하 약제 조성물

Publications (1)

Publication Number Publication Date
WO1998042350A1 true WO1998042350A1 (fr) 1998-10-01

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/KR1997/000127 WO1998042350A1 (fr) 1997-03-21 1997-06-27 Composition pharmaceutique abaissant le taux de cholesterol

Country Status (3)

Country Link
KR (1) KR19980074710A (fr)
AU (1) AU3192397A (fr)
WO (1) WO1998042350A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004009094A1 (fr) * 2002-07-24 2004-01-29 Ohio University Methodes et compositions permettant de traiter les diabetes sucres
WO2005070943A1 (fr) * 2004-01-23 2005-08-04 Ohio University Separation et purification de pgg

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20030075947A (ko) * 2002-03-19 2003-09-26 제네티카 주식회사 신 혈관형성을 억제하는 물질

Citations (12)

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JPS61100517A (ja) * 1984-10-19 1986-05-19 Nissan Chem Ind Ltd 新規齲蝕用剤
JPS61106515A (ja) * 1984-10-29 1986-05-24 Osaka Chem Lab ホルモンバランス調整食品
JPS63104927A (ja) * 1986-10-21 1988-05-10 Tsumura & Co アルド−スリダクタ−ゼ阻害剤
WO1990004968A1 (fr) * 1988-10-31 1990-05-17 University Of North Carolina At Chapel Hill Inhibition de retrovirus humains
JPH045237A (ja) * 1990-04-24 1992-01-09 Nonogawa Shoji Kk スーパーオキシド消去剤
JPH0436238A (ja) * 1990-06-01 1992-02-06 Takasago Internatl Corp 尋常性▲ざ▼瘡用皮膚外用剤
JPH0495020A (ja) * 1990-08-10 1992-03-27 Earth Chem Corp Ltd 酵素阻害剤
JPH06107555A (ja) * 1992-04-17 1994-04-19 Chong-Kook Kim 牛黄清心マイクロカプセル及びその製造方法
JPH07238025A (ja) * 1994-02-25 1995-09-12 Pola Chem Ind Inc 動脈硬化抑制剤及びこれを含む食品又は医薬
EP0753305A1 (fr) * 1995-07-13 1997-01-15 Showa Shell Sekiyu Kabushiki Kaisha Composition anti-SIDA et procédé de traitement d'infections à VIH avec un agent anti-VIH contenant un médicament brut
JPH0971537A (ja) * 1995-09-05 1997-03-18 Pola Chem Ind Inc ３−ヒドロキシ−３−メチルグルタリルコエンザイムａリダクターゼ活性阻害剤

Patent Citations (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS59128329A (ja) * 1983-01-07 1984-07-24 Yasuo Tanaka 抗ウィルス剤
JPS61100517A (ja) * 1984-10-19 1986-05-19 Nissan Chem Ind Ltd 新規齲蝕用剤
JPS61106515A (ja) * 1984-10-29 1986-05-24 Osaka Chem Lab ホルモンバランス調整食品
JPS63104927A (ja) * 1986-10-21 1988-05-10 Tsumura & Co アルド−スリダクタ−ゼ阻害剤
WO1990004968A1 (fr) * 1988-10-31 1990-05-17 University Of North Carolina At Chapel Hill Inhibition de retrovirus humains
JPH045237A (ja) * 1990-04-24 1992-01-09 Nonogawa Shoji Kk スーパーオキシド消去剤
JPH0436238A (ja) * 1990-06-01 1992-02-06 Takasago Internatl Corp 尋常性▲ざ▼瘡用皮膚外用剤
JPH0495020A (ja) * 1990-08-10 1992-03-27 Earth Chem Corp Ltd 酵素阻害剤
JPH06107555A (ja) * 1992-04-17 1994-04-19 Chong-Kook Kim 牛黄清心マイクロカプセル及びその製造方法
JPH07238025A (ja) * 1994-02-25 1995-09-12 Pola Chem Ind Inc 動脈硬化抑制剤及びこれを含む食品又は医薬
EP0753305A1 (fr) * 1995-07-13 1997-01-15 Showa Shell Sekiyu Kabushiki Kaisha Composition anti-SIDA et procédé de traitement d'infections à VIH avec un agent anti-VIH contenant un médicament brut
JPH0971537A (ja) * 1995-09-05 1997-03-18 Pola Chem Ind Inc ３−ヒドロキシ−３−メチルグルタリルコエンザイムａリダクターゼ活性阻害剤

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004009094A1 (fr) * 2002-07-24 2004-01-29 Ohio University Methodes et compositions permettant de traiter les diabetes sucres
WO2005070943A1 (fr) * 2004-01-23 2005-08-04 Ohio University Separation et purification de pgg
CN1930178B (zh) * 2004-01-23 2010-06-23 俄亥俄州立大学 Pgg的分离和纯化
US8357796B2 (en) 2004-01-23 2013-01-22 Ohio University PGG separation and purification

Also Published As

Publication number Publication date
KR19980074710A (ko) 1998-11-05
AU3192397A (en) 1998-10-20

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