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WO2007059685A1 - Calycosine d'astragalus a fonction de resistance contre le coxackievirus - Google Patents

Calycosine d'astragalus a fonction de resistance contre le coxackievirus Download PDF

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Publication number
WO2007059685A1
WO2007059685A1 PCT/CN2006/002910 CN2006002910W WO2007059685A1 WO 2007059685 A1 WO2007059685 A1 WO 2007059685A1 CN 2006002910 W CN2006002910 W CN 2006002910W WO 2007059685 A1 WO2007059685 A1 WO 2007059685A1
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WO
WIPO (PCT)
Prior art keywords
drug
virus
present
viral myocarditis
mice
Prior art date
Application number
PCT/CN2006/002910
Other languages
English (en)
Chinese (zh)
Inventor
Chenggang Huang
Yuanyuan Zhang
Haiyan Zhu
Chunhui Ma
Guan Ye
Mingsong Fan
Yihong Tang
Zhixiong Li
Zhaolin Sun
Original Assignee
Shanghai Institute Of Materia Medica, Chinese Academy Of Sciences
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 Shanghai Institute Of Materia Medica, Chinese Academy Of Sciences filed Critical Shanghai Institute Of Materia Medica, Chinese Academy Of Sciences
Publication of WO2007059685A1 publication Critical patent/WO2007059685A1/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
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
    • 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
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system

Definitions

  • the invention relates to extracting active ingredients from traditional Chinese medicines, and is proved to be effective for treating viral myocarditis by pharmacological tests, more specifically, extracting and isolating an isoflavone active ingredient from the radix astragali or other traditional Chinese medicines - verapamil isotope - 7 - oxygen - D - Calycosin 7-0- ⁇ -D- glucoside, which can be used in the preparation of a drug against Coxsackie virus and a disease caused by Coxsackie virus.
  • Background technique
  • Coxsackievirus can cause a variety of diseases, such as viral myocarditis, epidemic chest pain, aseptic encephalitis, meningitis, Keshan disease and viral epilepsy, which seriously endanger human health.
  • Coxsackie virus diseases such as viral myocarditis
  • the main method for clinical treatment of Coxsackie virus diseases such as viral myocarditis is to use common antiviral drugs, immunosuppressants, interferons and cardiomyocyte nutrients, but the curative effect is not satisfactory.
  • Patent CN01126608. 2 discloses that isoflavones and glycoside have good anti-ischemic effect; Patent CN00119451. 8 discloses the use of astragaloside IV in the treatment of viral myocarditis; patent CN01126609. 0 discloses that astragaloside has anti-myocardial fibrosis. No reports of vermiculone isoflavone-7-oxo- ⁇ -D-glucopyranoside against Coxsackie Virus and treatment of viral myocarditis. Summary of the invention
  • the object of the present invention is to overcome the shortcomings of the conventional multi-flavored decoction, and to chemically separate the isoflavone active ingredient - the isoflavone - 7-oxo- ⁇ -D-glucopyranoside, from the astragalus or other traditional Chinese medicine.
  • Pharmacological tests are applied to the preparation of anti-coxsackie virus and drugs for the treatment of viral myocarditis.
  • the medicament of the present invention can be prepared by the following method: After pulverization of astragalus or other Chinese medicinal materials, three times (2 hours, one hour, one hour) of refluxing with 70% ethanol, filtering, combining the filtrates, recovering the solvent under reduced pressure, and concentrating to an alcohol-free taste. , obtained xanthine extract I.
  • the extract I was mixed with water and filtered, and the filtrate was adsorbed with a macroporous resin, and the impurities were eluted with water, and then eluted with 70% ethanol, and the eluate was concentrated under reduced pressure to obtain an extract II.
  • the extract II was separated by silica gel column chromatography, eluting with a gradient of chloroform-methanol, and the same fractions were combined, evaporated to dryness, and the solvent was evaporated to dryness, and the mixture was allowed to stand, and the white powder was precipitated and filtered to obtain white powdery crystals. That is, the compound of the present invention, carophyllin 7-O- ⁇ -D-glucoside, is obtained.
  • the structure is as follows:
  • the molecular formula is 22 ⁇ .
  • the molecular weight is 446, and the chemical name is 3'-hydroxy-4'-methoxyisoflavone-7-oxo- ⁇ -D-glucopyranoside.
  • the isoflavone-7-oxo- ⁇ -D-glucopyranoside obtained by the above method is first tested for efficacy.
  • results of the in vitro antiviral test performed on primary cultured cardiomyocytes indicate the TC 5 of the drug of the present invention.
  • the therapeutic index (TI) was 10.00, indicating that the drug of the present invention has a significant inhibitory effect on CVB 3 virus in vitro.
  • a model of viral myocarditis was established by intraperitoneal vaccination with Coxsackie B3 virus in Balb/c mice.
  • the drug-administered 40 mg/kg and 20 mg/kg were administered intragastrically in the high- and low-dose groups.
  • the model control group and the normal control group were administered.
  • the rats were given the same amount of normal saline for 12 days. On the 15th day, the mice were observed for color, eating, and death. The results showed that the two dose groups were significantly reduced by the Coxsackie B 3 virus.
  • the mortality of mice caused by viral myocarditis significantly reduced the heart index of mice with viral myocarditis, and effectively decreased the serum levels of LDH and GOT in mice with viral myocarditis caused by Coxsackie B3 virus.
  • test method refers to "Modern Pharmacological Experimental Methods" (Volume 2, P 1425 , edited by Zhang Juntian, Beijing Medical University, China Union Medical University, United Press, 1998 edition). ' detailed description
  • Example 1 Preparation of the medicament of the present invention Take the Astragalus membranaceus, pulverize, extract three times with 70% ethanol reflux (2 hours, 1 hour, 1 hour), filter, combine the filtrate, recover the solvent under reduced pressure, and concentrate to a non-alcoholic taste to obtain a xanthine extract I.
  • the extract I was mixed with water and filtered, and the filtrate was adsorbed with a macroporous resin (AB-8 type), and the impurities were eluted with water, and then eluted with 70% ethanol, and the eluate was concentrated under reduced pressure to obtain an extract II.
  • a macroporous resin AB-8 type
  • Extract II was chromatographed on a 200-300 mesh silica gel column, eluting with chloroform-methanol gradient, TLC detection, 10% sulfuric acid-ethanol color development, combining the same fractions, evaporated to dryness, methanol hot solution, standing, white floc The precipitated material was filtered off with suction to give a white powdery crystal.
  • Example 2 Effect of the drug of the present invention on coxsackievirus (CV)-infected cardiomyocytes (in vitro)
  • Normal control group Add culture medium per well 1. 0ml;
  • Dosing group A gradient dilution of the drug solution of the present invention was added. OmL/well, four replicate wells per dilution.
  • the cell survival was observed under an inverted phase contrast microscope, and the TC 5 of the primary cultured cardiomyocytes of the drug of the present invention was calculated according to the Reed-Mench method. .
  • Normal control group adding culture solution per well l.
  • the administration group 0.2 ml of CVB 3 virus solution (TCID ⁇ IO" 4 - 56 , 10 -5 dilution) was added to each well, and the mixture was incubated for 1 hour, the supernatant was discarded, and washed three times with PBS solution, and the gradient dilution was added to the present invention.
  • Drug solution l. OraL/well, four replicate wells per dilution.
  • Cardiomyocytes will slowly die in culture, pseudopods break, cells shrink, round, and the refractive index increases. The cell death was significantly increased after being infected by the virus, and a large area of necrosis was observed. If the drug is effective after administration, the mortality of the virus-infected cells can be reduced.
  • the IC 5 of the drug of the present invention against primary cultured cardiomyocytes was calculated according to the Reed- Muench method. . ⁇
  • TC 5 of the medicament of the invention It is 177. 84 ug/ml, and 1 for CVB 3 virus.
  • the therapeutic index (TI) was 10.00, which was 17.78 ug/ml, indicating that the drug of the present invention has a significant inhibitory effect on CVB 3 virus in vitro.
  • Example 3 Effect of the drug of the present invention on mortality of mice with viral myocarditis (in vivo)
  • the drug of the present invention was divided into two dose groups, and Balb/c mice were randomly divided into 4 groups:
  • Normal control group intraperitoneal inoculation 0. 1ml normal saline, daily, equal amount of normal saline;
  • the drug group I of the present invention has a high dose: the same method as the above method of inoculation of CVB 3 virus solution, the same day, the drug solution of the invention 40mg / kg • d, continuous administration for 12 days;
  • the pharmaceutical group II of the present invention has a low dose: the same as the third group method, the drug solution of the present invention is administered at a dose of 20 mg/kg*d, and is continuously administered for 12 times;
  • mice After observing for 15 days, various conditions such as mouse color and eating were observed, and the mortality of each group of mice was counted.
  • Virus control group 15 40% (6) 'The drug group of the invention I 15 26. 7% (4) *
  • Example 4 Effect of the drug of the present invention on heart index of mice with viral myocarditis (in vivo)
  • mice were grouped and dosed as in Example 2. After 12 days of continuous administration, on the 15th day, all the mice were dissected. The body weight of the mouse was weighed before dissection, and then the heart weight was weighed.
  • Heart index heart weight / weight
  • the heart index can be used to measure the degree of heart disease. The greater the heart index, the more severe the heart disease becomes.
  • Virus control group 5. 60 ⁇ 0. 73
  • the drug group of the invention I 5. 05 ⁇ 0. 63*
  • the medicament of the invention II 5. 14 ⁇ 0. 58*
  • the drug-administered group is compared with the virus group: * p ⁇ 0. 05, ** p ⁇ 0. 01
  • Example 5 Effect of the drug of the present invention on serum LDH and GOT contents in mice with viral myocarditis (in vivo) Balb/c mice were grouped and administered at the same dose as in Example 2. After 12 days of continuous administration, on the 15th day, blood was taken from the eyeball, and serum was centrifuged to measure the contents of lactate dehydrogenase (LDH) and aspartate aminotransferase (GOT) in the serum.
  • LDH lactate dehydrogenase
  • GOT aspartate aminotransferase
  • Aspartate aminotransferase and lactate dehydrogenase are biochemical markers of myocardial damage. In the acute phase of viral myocarditis, both release are elevated and can be maintained for a considerable period of time. Therefore, if the drug can effectively reduce the myocardial enzyme spectrum, it means that the drug effectively reduces the degree of heart disease.
  • the drug group of the present invention I 459.18 ⁇ 51.31* 21.65 ⁇ 5.00*
  • the drug group of the present invention I 459.18 ⁇ 51.31* 21.65 ⁇ 5.00*

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Cardiology (AREA)
  • Molecular Biology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Virology (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines Containing Plant Substances (AREA)

Abstract

L'invention concerne l'activité antivirale du calycosine 7-O-β-D-glucoside de l'Astragalus contre le Coxackievirus, et l'application du calycosine 7-O-β-D-glucoside dans le développement de la médecine pour le traitement de la myocardite virale par le Coxackievirus.
PCT/CN2006/002910 2005-11-23 2006-10-30 Calycosine d'astragalus a fonction de resistance contre le coxackievirus WO2007059685A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN2005101106413A CN1813711B (zh) 2005-11-23 2005-11-23 一种异黄酮类化合物的用途
CN200510110641.3 2005-11-23

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WO2007059685A1 true WO2007059685A1 (fr) 2007-05-31

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WO (1) WO2007059685A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112057628A (zh) * 2020-08-25 2020-12-11 湖北民族大学 一种抗肿瘤药物盒

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101143861B (zh) * 2006-09-15 2011-08-03 中国科学院上海药物研究所 一类b环4’-单取代黄酮化合物在制备抗柯萨奇b病毒感染的药物中的用途
CN101139378B (zh) * 2007-10-24 2010-12-15 中国农业大学 一种从黄芪中提取毛蕊异黄酮-7-O-β-D-葡萄糖苷的方法
CN101780069B (zh) * 2009-01-16 2012-08-22 广州康臣药物研究有限公司 一种防治糖尿病肾病的药物组合物及其制备方法
CN102133262A (zh) * 2011-03-13 2011-07-27 浙江大学 具心肌保护作用的黄芪有效组分制备方法与用途
CN102532221A (zh) * 2011-12-29 2012-07-04 广西壮族自治区药用植物园 黄芪中毛蕊异黄酮苷的提取与纯化方法

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1403452A (zh) * 2001-08-31 2003-03-19 上海中医药大学 具有抗心肌缺血作用的黄芪毛蕊异黄酮及其糖甙

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1403452A (zh) * 2001-08-31 2003-03-19 上海中医药大学 具有抗心肌缺血作用的黄芪毛蕊异黄酮及其糖甙

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
DING JIJUN ET AL.: "The effect of astragalus saponins on mice viral myocarditis caused by CVB 3", ACADEMIC JOURNAL OF SECOND MILITARY MEDICAL UNIVERSITY (CHINESE), vol. 20, no. 9, 1999, pages 666 - 668, XP003013908 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112057628A (zh) * 2020-08-25 2020-12-11 湖北民族大学 一种抗肿瘤药物盒
CN112057628B (zh) * 2020-08-25 2023-01-17 湖北民族大学 一种抗肿瘤药物盒

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CN1813711A (zh) 2006-08-09

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