WO2009143662A1 - Composition pharmaceutique comprenant un agent bloquant du canal de calcium et des vitamines de la famille b et utilisation de celle-ci - Google Patents

Composition pharmaceutique comprenant un agent bloquant du canal de calcium et des vitamines de la famille b et utilisation de celle-ci Download PDF

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Publication number
WO2009143662A1
WO2009143662A1 PCT/CN2008/001681 CN2008001681W WO2009143662A1 WO 2009143662 A1 WO2009143662 A1 WO 2009143662A1 CN 2008001681 W CN2008001681 W CN 2008001681W WO 2009143662 A1 WO2009143662 A1 WO 2009143662A1
Authority
WO
WIPO (PCT)
Prior art keywords
vitamin
daily dosage
calcium channel
channel blocker
folic acid
Prior art date
Application number
PCT/CN2008/001681
Other languages
English (en)
Chinese (zh)
Inventor
徐希平
秦献辉
陈光亮
王文艳
于多
王燕
Original Assignee
北京奥萨医药研究中心有限公司
深圳奥萨医药有限公司
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 CNA2008101142146A external-priority patent/CN101590235A/zh
Priority claimed from CNA2008101142165A external-priority patent/CN101590237A/zh
Application filed by 北京奥萨医药研究中心有限公司, 深圳奥萨医药有限公司 filed Critical 北京奥萨医药研究中心有限公司
Publication of WO2009143662A1 publication Critical patent/WO2009143662A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • 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
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4422—1,4-Dihydropyridines, e.g. nifedipine, nicardipine
    • 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
    • A61K31/7135—Compounds containing heavy metals
    • A61K31/714—Cobalamins, e.g. cyanocobalamin, i.e. vitamin B12
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods

Definitions

  • Hcy is closely related to ischemic heart disease, stroke, and deep vein thrombosis [Wald DS, et al. Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis. BMJ. 2002; 325: 1202-1206.] .
  • AD Alzheimer's disease
  • PD Parkinson's disease
  • Various diseases such as schizophrenia, death, neonatal defects, and habitual abortion are closely related.
  • Hcy levels are positively correlated with the damage caused.
  • the Hcy level of healthy people abroad is about 8-10 mol L.
  • the Hcy level is greater than or equal to 10 ⁇ /L, which is defined as high Hcyemia or elevated Hcy [Circulation, 2006; 113: e409-e449; Clin Chem Med. 2003; 41 : 1392-1403].
  • cinnarizine flunarizine, preferably schopenthalide, amlodipine, levamlodipine, nitrendipine, more preferably amlodipine, levoammonium chloride
  • Adipine and nifedipine are more preferred amlodipine.
  • Metabolites or salts of calcium channel blockers such as derivative, metabolite, precursor or calcium channel blocker active metabolites with calcium channel blockers as active ingredients, are also included in the scope of the present disclosure. .
  • the daily dosage of calcium channel blockers is: nifedipine 20 ⁇ 120mg, amlodipine 2.5 ⁇ 20mg, levamlodipine 2.5 ⁇ 10mg, nicardipine 30 ⁇ 240mg, lacidipine 2 ⁇ 8mg Nitrodipine 5 ⁇ 60mg, nitrendipine 10 ⁇ 60mg, felodipine 2.5 ⁇ 40mg, isradipine 2.5 ⁇ 20mg, diltiazem 30 ⁇ 240mg, verapamil 40 ⁇ 480mg, etc.
  • the content of the derivative, precursor, active metabolite or salt of the above substance can be obtained by equivalent conversion of the above substances.
  • the daily amount of the derivative, precursor, active metabolite or salt of the above substance can be determined by equivalent conversion of the above substance.
  • the preferred daily dosages of calcium channel blockers are: nifedipine 20 ⁇ 60mg, amlodipine 2.5 ⁇ 10mg, levamlodipine 2.5 ⁇ 5mg, nicardipine 60 ⁇ : L20mg, lacidipine 4 ⁇ 6mg, nisoldipine 10 ⁇ 60mg, nitrendipine 20 ⁇ 60mg, felodipine 2.5 ⁇ 20mg, yira Level 2.5 ⁇ 10mg, diltiazem 90 ⁇ 240mg, verapamil 80 ⁇ 360mg, etc.
  • the daily usage of the derivatives, precursors, active metabolites or salts of the above substances can be determined by equivalent conversion of the above substances.
  • the calcium channel blocker is levamlodipine, and the daily dosage is 25 mg; the B vitamin is folic acid or calcium leucovorin, and the daily dosage is 0.2 to 5 mg.
  • the calcium channel blocker is lacidipine, the daily use I is 4 ⁇ 6mg; the B vitamin is folic acid or calcium leucovorin, and the daily dosage is 0.2 -"5mgc
  • the drug The composition may be in the form of a pharmaceutical preparation, including but not limited to common tablets, bilayer tablets, multi-layer tablets, sustained release tablets, single-chamber controlled release tablets, dual-chamber controlled release tablets, micropores Controlled release tablets, sublingual tablets, orally disintegrating tablets, dispersible tablets, enteric coated tablets, granules, pills, enteric capsules, delayed release tablets, timed/release tablets, ordinary capsules, sustained release capsules, controlled Capsules, capsules containing pellets or tablets, pH-dependent capsules containing micropellets or tablets, oral liquids, films or patches. Special mention should be made of drugs containing calcium channel blockers and B vitamins. The composition is made into a tablet or capsule.
  • the calcium channel blocker is nifedipine, and the daily dosage is 20 to 60 parts by weight; the B group vitamin is folic acid or calcium tetrahydrofolate, and the daily amount is 0.2 to 5 parts by weight.
  • Oral administration was started from the 5th week of modeling, amlodipine low dose group, amlodipine high dose group, folic acid group and amlodipine + folic acid group were given amlodipine daily.
  • the SOD level in the model group was significantly reduced, and the MDA level was significantly increased, indicating that oxidative damage is one of the major damage pathways of high Hcy.
  • One of the most important markers of vascular endothelial injury and dysfunction is the decrease in NO levels.
  • the level of NO in the model group was significantly reduced, indicating that endothelial cell injury is also an important pathway for high Hcyemia leading to body damage.

Landscapes

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

Abstract

La présente invention concerne une composition pharmaceutique qui contient un agent bloquant du canal de calcium et des vitamines de la famille B et l’utilisation de la composition dans le traitement de l’hyperhomocystéinémie. La combinaison d’agent bloquant du canal de calcium et de vitamines de la famille B peut agir sur des voies et liens multiples de l’hyperhomocystéinémie, diminuer efficacement les dommages pour l’organisme et diminuer le taux d’homocystéine et est supérieure au médicament individuel, ce qui met en évidence l’effet significativement synergique d’un agent bloquant du canal de calcium et de vitamines de la famille B sur l’abaissement d’un taux élevé d’homocystéine et l’atténuation des dommages causés par un taux élevé d’homocystéine.
PCT/CN2008/001681 2008-05-30 2008-09-28 Composition pharmaceutique comprenant un agent bloquant du canal de calcium et des vitamines de la famille b et utilisation de celle-ci WO2009143662A1 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
CNA2008101142146A CN101590235A (zh) 2008-05-30 2008-05-30 含有钙拮抗剂和b族维生素的组合物及其用途
CN200810114214.6 2008-05-30
CNA2008101142165A CN101590237A (zh) 2008-05-30 2008-05-30 含有钙拮抗剂和叶酸的组合物的用途
CN200810114216.5 2008-05-30

Publications (1)

Publication Number Publication Date
WO2009143662A1 true WO2009143662A1 (fr) 2009-12-03

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2008/001681 WO2009143662A1 (fr) 2008-05-30 2008-09-28 Composition pharmaceutique comprenant un agent bloquant du canal de calcium et des vitamines de la famille b et utilisation de celle-ci

Country Status (1)

Country Link
WO (1) WO2009143662A1 (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102579451A (zh) * 2012-01-20 2012-07-18 孙飏 一种药物组合物及其用途和包装
CN103599537A (zh) * 2013-11-15 2014-02-26 深圳奥萨医药有限公司 钙通道阻滞剂/噻嗪类利尿剂/5-甲基四氢叶酸药物组合物
CN111481554A (zh) * 2019-01-29 2020-08-04 深圳奥萨医药有限公司 含氨氯地平和叶酸的片剂及其制备方法

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1186665A (zh) * 1996-12-27 1998-07-08 田玉琦 活脑心胶囊
CN1751689A (zh) * 2005-09-06 2006-03-29 北京思普润安医药科技有限公司 一种含有阿司匹林的药物组合物的制备方法
CN1824320A (zh) * 2005-01-13 2006-08-30 安徽省生物医学研究所 含有钙通道阻滞剂和b族维生素的药物组合物及其用途
CN1930961A (zh) * 2006-09-29 2007-03-21 中国人民解放军第三军医大学第一附属医院 常温亚常温离体心脏灌注保存液

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1186665A (zh) * 1996-12-27 1998-07-08 田玉琦 活脑心胶囊
CN1824320A (zh) * 2005-01-13 2006-08-30 安徽省生物医学研究所 含有钙通道阻滞剂和b族维生素的药物组合物及其用途
CN1751689A (zh) * 2005-09-06 2006-03-29 北京思普润安医药科技有限公司 一种含有阿司匹林的药物组合物的制备方法
CN1930961A (zh) * 2006-09-29 2007-03-21 中国人民解放军第三军医大学第一附属医院 常温亚常温离体心脏灌注保存液

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102579451A (zh) * 2012-01-20 2012-07-18 孙飏 一种药物组合物及其用途和包装
CN103599537A (zh) * 2013-11-15 2014-02-26 深圳奥萨医药有限公司 钙通道阻滞剂/噻嗪类利尿剂/5-甲基四氢叶酸药物组合物
CN111481554A (zh) * 2019-01-29 2020-08-04 深圳奥萨医药有限公司 含氨氯地平和叶酸的片剂及其制备方法
CN111481554B (zh) * 2019-01-29 2022-11-25 深圳奥萨医药有限公司 含氨氯地平和叶酸的片剂及其制备方法

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