WO2021249237A1 - Triépoxyhexahydrochromone a, composition pharmaceutique et utilisation associée - Google Patents

Triépoxyhexahydrochromone a, composition pharmaceutique et utilisation associée Download PDF

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Publication number
WO2021249237A1
WO2021249237A1 PCT/CN2021/097616 CN2021097616W WO2021249237A1 WO 2021249237 A1 WO2021249237 A1 WO 2021249237A1 CN 2021097616 W CN2021097616 W CN 2021097616W WO 2021249237 A1 WO2021249237 A1 WO 2021249237A1
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WO
WIPO (PCT)
Prior art keywords
pharmaceutical composition
silica gel
preparation
ethyl acetate
triepoxyhexahydrochromone
Prior art date
Application number
PCT/CN2021/097616
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English (en)
Chinese (zh)
Inventor
王跃虎
罗吉凤
何倩
张璐
夏梦媛
Original Assignee
中国科学院昆明植物研究所
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Publication of WO2021249237A1 publication Critical patent/WO2021249237A1/fr

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
    • C07D493/22—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains four or more hetero rings
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16—Anti-Parkinson drugs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/07—Optical isomers

Definitions

  • the invention belongs to the technical field of medicine, and particularly relates to a triepoxyhexahydrochromone A compound and its pharmaceutical composition and its application in the preparation of drugs for preventing and treating Parkinson's disease.
  • the PC12 cell injury model induced by 1-methyl-4-phenyl pyridinium ion (MPP + ) is currently recognized as a screening model for the treatment of Parkinson’s disease [a.Delavar MR, Baghi M,Safaeinejad Z,Kiani-Esfahani A,Ghaedi K,Nasr-Esfahani MH.Differential expression of miR-34a,miR-141,and miR-9 in MPP + -treated differentiated PC12 cells as a model of Parkinson's disease.Gene ,2018,662:54-65; b.Lin KH,Li CY,Hsu YM,Tsai CH,Tsai FJ,Tang CH,Yang JS,Wang ZH,Yin MC.Oridonin,a natural diterpenoid,protected NGF-differentiated PC12 cells against MPP + -and kainic acid-induced injury. Food and
  • the purpose of the present invention is to provide a new compound triepoxyhexahydrochromone A (PFC-34) and its pharmaceutical composition and its application in the preparation of prevention and treatment of neurodegenerative diseases and/or Parkinson's disease.
  • the present invention provides the following technical solutions:
  • the pharmaceutical composition consists of triepoxyhexahydrochromone A and a pharmaceutically acceptable carrier.
  • the pharmaceutical composition for preventing and treating neurodegenerative diseases and/or Parkinson's disease is composed of triepoxyhexahydrochromone A and a pharmaceutically acceptable carrier.
  • the dietary supplement composition is composed of triepoxyhexahydrochromone A and food supplements.
  • triepoxyhexahydrochromone A in the preparation of drugs for preventing and/or treating neurodegenerative diseases.
  • triepoxyhexahydrochromone A in the preparation of drugs for preventing and/or treating Parkinson's disease.
  • the preparation method of triepoxyhexahydrochromone A includes the following steps: pulverize dried agarwood, 90% ethanol at 60°C ultrasonic extraction for 30 minutes, finally obtain a concentrated crude extract extract, and then suspend the extract in water, Extract with equal volumes of petroleum ether, ethyl acetate and n-butanol in sequence, and recover the solvent to obtain petroleum ether extract, ethyl acetate extract, and n-butanol extract; use the same amount of 80-100 for the ethyl acetate extraction part Mix the sample with the mesh silica gel and divide it by normal phase silica gel column chromatography.
  • the eluent is petroleum ether-ethyl acetate system (50:1, 30:1, 20:1, 10:1, 5:1, 3:1) , 2:1, 1:1, 0:1, v/v) for gradient elution, followed by ethyl acetate-methanol system for elution (5:1, 3:1, 2:1, 1:1, 0:1, v/v), the same components were combined by TLC detection to obtain 5 parts Fr.Y-1 ⁇ Fr.Y-5; Fr.Y-4 was subjected to medium pressure RP-18 reversed-phase silica gel column chromatography (Methanol-water, 10% ⁇ 100%), the same fractions were combined by TLC detection to obtain 4 parts Fr.Y-4-1 ⁇ Fr.Y-4-4; Fr.Y-4-3 was tested by Sephadex LH- 20 gel column chromatography (methanol), normal phase silica gel column chromatography (300-400 mesh silica gel; petroleum ether-ethyl acetate, 50:1 ⁇ 1:1, v/v), to obtain
  • composition prepared by the compound of the present invention and its pharmaceutically acceptable carrier can be administered orally or without oral administration.
  • the dosage varies with different drugs. For adults, 1-100 mg per day is more appropriate. .
  • parenteral administration can be administered in the form of injections, infusions or suppositories.
  • conventional formulation techniques can be used.
  • the dried Chinese medicine Aquilaria sinensis [namely the heartwood of Aquilaria sinensis (Lour.) Spreng.; 2.9kg] was crushed, and ultrasonically extracted with 90% ethanol at 60°C for 30 minutes, and finally a concentrated crude extract extract (459.3g) was obtained. Then the extract was suspended in water, extracted with equal volumes of petroleum ether, ethyl acetate, and n-butanol in sequence, and the solvent was recovered to obtain 0.7 g of petroleum ether extract, 374.8 g of ethyl acetate extract, and 52.5 g of n-butanol extract. .
  • the ethyl acetate extract (374.8g) was mixed with an equal amount of 80-100 mesh silica gel and segmented by normal phase silica gel column chromatography.
  • the eluent was a petroleum ether-ethyl acetate system (50:1, 30:1). , 20:1, 10:1, 5:1, 3:1, 2:1, 1:1, 0:1, v/v) for gradient elution, followed by ethyl acetate-methanol system for elution ( 5:1, 3:1, 2:1, 1:1, 0:1, v/v), the same components were combined by TLC detection to obtain 5 parts (Fr.Y-1 ⁇ Fr.Y-5) .
  • Fr.Y-4 (35.9g) was subjected to medium pressure RP-18 reversed-phase silica gel column chromatography (methanol-water, 10% ⁇ 100%), and the same fractions were combined by TLC detection to obtain 4 fractions (Fr.Y-4 -1 ⁇ Fr.Y-4-4).
  • Fr.Y-4-3 (2.3g) was subjected to Sephadex LH-20 gel column chromatography (methanol), normal phase silica gel column chromatography (300-400 mesh silica gel; petroleum ether-ethyl acetate, 50:1 ⁇ 1: 1, v/v), 4 parts (Fr.Y-4-3-1 ⁇ Fr.Y-4-3-4) are obtained.
  • Blank group only medium
  • Compound group (group 1 to group 5): add compound PFC-34 at a final concentration of 5, 2, 1, 0.2, 0.1 ⁇ M to the medium, and then add MPP + at a final concentration of 750 ⁇ M.
  • the oral liquid is prepared according to the conventional oral liquid preparation method.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Psychology (AREA)
  • Hospice & Palliative Care (AREA)
  • Psychiatry (AREA)
  • Botany (AREA)
  • Mycology (AREA)
  • Nutrition Science (AREA)
  • Food Science & Technology (AREA)
  • Polymers & Plastics (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne un triépoxyhexahydrochromone A (PFC-34), et une composition pharmaceutique de celui-ci ainsi que son utilisation dans la préparation d'un médicament pour la prévention et le traitement de maladies neurodégénératives et de la maladie de Parkinson. Le triépoxyhexahydrochromone A (PFC-34) a un effet protecteur significatif sur les dommages PC12 induits par MPP +, et peut être utilisé dans la préparation d'une composition pharmaceutique ou d'une composition de complément alimentaire pour prévenir et traiter la maladie de Parkinson.
PCT/CN2021/097616 2020-06-08 2021-06-01 Triépoxyhexahydrochromone a, composition pharmaceutique et utilisation associée WO2021249237A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN202010512429.4 2020-06-08
CN202010512429.4A CN111647003B (zh) 2020-06-08 2020-06-08 三环氧六氢色酮a及其药物组合物和其应用

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WO2021249237A1 true WO2021249237A1 (fr) 2021-12-16

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Cited By (1)

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CN111647003A (zh) * 2020-06-08 2020-09-11 中国科学院昆明植物研究所 三环氧六氢色酮a及其药物组合物和其应用

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CN115177613A (zh) * 2022-07-27 2022-10-14 云南民族大学 含木脂素类化合物futoenone的药物组合物和其应用

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CN111647003A (zh) * 2020-06-08 2020-09-11 中国科学院昆明植物研究所 三环氧六氢色酮a及其药物组合物和其应用
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