CN1859902A - 抗动脉粥样血栓形成剂与抗血小板凝集剂的新组合产品 - Google Patents

抗动脉粥样血栓形成剂与抗血小板凝集剂的新组合产品 Download PDF

Info

Publication number
CN1859902A
CN1859902A CNA2004800283560A CN200480028356A CN1859902A CN 1859902 A CN1859902 A CN 1859902A CN A2004800283560 A CNA2004800283560 A CN A2004800283560A CN 200480028356 A CN200480028356 A CN 200480028356A CN 1859902 A CN1859902 A CN 1859902A
Authority
CN
China
Prior art keywords
pharmaceutical composition
clopidogrel
chemical compound
combination product
pharmaceutically
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.)
Granted
Application number
CNA2004800283560A
Other languages
English (en)
Other versions
CN100453075C (zh
Inventor
L·克洛阿雷克-布兰查德
S·科达
L·勒龙
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.)
Les Laboratoires Servier SAS
Original Assignee
Les Laboratoires Servier SAS
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 Les Laboratoires Servier SAS filed Critical Les Laboratoires Servier SAS
Publication of CN1859902A publication Critical patent/CN1859902A/zh
Application granted granted Critical
Publication of CN100453075C publication Critical patent/CN100453075C/zh
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

Links

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
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/18—Sulfonamides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
    • C07C311/15—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings
    • C07C311/20—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to a carbon atom of a ring other than a six-membered aromatic ring
    • 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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • 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
    • A61K31/4353—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 ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/4365—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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system having sulfur as a ring hetero atom, e.g. ticlopidine
    • 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
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/4743—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having sulfur as a ring hetero atom
    • 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
    • A61K31/63—Compounds containing para-N-benzenesulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonyl hydrazide
    • 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
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • 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
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • 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
    • A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
    • 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
    • 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
    • A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
    • 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
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • 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
    • A61P9/12—Antihypertensives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
    • C07C311/15—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings
    • C07C311/21—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
    • C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D495/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2602/00—Systems containing two condensed rings
    • C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
    • C07C2602/04—One of the condensed rings being a six-membered aromatic ring
    • C07C2602/10—One of the condensed rings being a six-membered aromatic ring the other ring being six-membered, e.g. tetraline

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Organic Chemistry (AREA)
  • Epidemiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Cardiology (AREA)
  • Diabetes (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Hematology (AREA)
  • Urology & Nephrology (AREA)
  • Vascular Medicine (AREA)
  • Physiology (AREA)
  • Nutrition Science (AREA)
  • Hospice & Palliative Care (AREA)
  • Emergency Medicine (AREA)
  • Endocrinology (AREA)
  • Obesity (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Investigating Or Analysing Biological Materials (AREA)

Abstract

本发明涉及一种抗动脉粥样血栓形成剂与抗血小板凝集剂的新组合产品。

Description

抗动脉粥样血栓形成剂与抗血小板凝集剂的新组合产品
本新发明涉及一种抗动脉粥样血栓形成剂与抗血小板凝集剂的新组合产品，还涉及含有它们的药物组合物。
更具体地讲，本发明涉及一种特异性TP受体拮抗剂和氯吡格雷的组合产品。
血栓烷A2(TXA2)是一种不稳定的花生四烯酸的代谢物，与许多心血管病的发病机制有关。血栓烷A2是一种强的血小板活化剂，且还是一种具有细胞增生和前粘连(pro-adhesive)性质的强血管收缩剂。
TXA2和其它花生四烯酸代谢物，例如内过氧化物(PGG2-PGH2)、HETEs和异前列腺烷，都通过称之为TP受体(血栓烷-前列腺素-内过氧化物)的共同受体显示作用。
近来人们进行了大量的研究工作，目的在于防止在心血管和神经血管系统中与过量产生血栓烷A2相关的现象。在这样一些拮抗剂中，发现在专利EP 648 741说明书中描述的那些拮抗剂是TP受体的强而有选择性的拮抗剂，通过口服途径给药，它们具有活性并作用时间长。
更特别地讲，申请人已发现呈外消旋形式或光学纯异构体形式的下式(I)化合物(A)及其在药学上可接受盐是强的抗动脉粥样血栓形成剂：
Figure A20048002835600041
化合物(A)是一种特异性TP受体拮抗剂，更特别地讲，是一种血栓烷A2和前列腺素-内过氧化物(PGG2-PGH2)受体的特异性拮抗剂，因此使该化合物具有强的动脉粥样化血栓形成作用。
一般而言，在动脉粥样化斑块破裂后，由于循环血小板与暴露于血流的血管内皮基层的胶原蛋白的相互作用导致血栓形成。这种现象称为动脉粥样化血栓形成。
胶原蛋白存在于血管壁的基层，并且是人和动物体内动脉粥样化病变血栓形成的决定因子。
血小板通过胶原蛋白受体粘附在胶原蛋白纤维上，并且还与血小板粘附、活化和凝集有关。
血小板活化伴随着释放两种主要的激动剂，即ADP和血栓烷A2，它们与相邻血小板上的各自受体(P2Y、TP)结合，使粘附作用和血小板凝集增强。
ADP作为一种循环介质也存在于血液中，而血栓烷A2是一种强的次要介质，它是在活化的血小板中通过环加氧酶1由花生四烯酸生成的。
血栓烷A2不仅促进血栓形成，而且还诱发血管壁机能不良(血管收缩)，促进血管壁增生和炎性浸润。
在目前可采用的抗血小板治疗中，阿司匹林能抑制由血栓烷A2产生血小板，同时氯吡格雷抑制由ADP诱发的血小板凝集。
ADP和血栓烷A2在动脉血栓形成中起到重要的补充作用。
化合物A通过阻断由血栓烷A2和其它TP受体配位体诱发的血小板凝集而起作用，无论其怎样的来源、血小板和血小板外也都如此。
它还通过抑制由血栓烷A2诱发的血管收缩和通过对抗血管壁的内皮机能不良和增生以及炎性而起作用。
申请人现在发现，在人体中，化合物A与氯吡格雷的组合产品具有令人惊奇的抗血栓形成协同作用。
事实上，由于化合物A与氯吡格雷以完全不同的凝集途径作用于血小板，因此，为了获得一种新的治疗方法，将这两种化合物结合起来是特别有利的。
申请人令人惊奇地发现，化合物A与氯吡格雷的组合产品就活性而言具有显著的协同作用，这一点并不能从任何已有的文献中得到启示。这种组合产品对于抗血栓形成作用的改善可通过离体对由胶原蛋白诱发的血小板凝集的抑制进行评价。
该试验表明，在氯吡格雷存在下，化合物A的抗血栓形成活性得到加强，并且以极其显著和完全不可预知的方式增加。此外，该组合产品具有良好的可接受性。
在本发明的组合产品中，化合物A与氯吡格雷可以呈药学上可接受的盐的形式。
在化合物A的加成盐中，可以提到与药学上可接受碱的加成盐，例如钠盐、钾盐、叔丁胺盐和二乙胺盐等，但并不限于此。
优选的盐是钠盐。
在氯吡格雷的加成盐中，优选硫酸氢盐。
在本发明的组合产品中，化合物A优选地具有绝对构型(R)。
本发明还涉及含有化合物A与氯吡格雷或者它们的药学上可接受的盐的组合产品的药物组合物，需要时，该药物组合物还可以含有一种或多种适当的惰性无毒赋形剂。
在本发明的药物组合物中，更具体地可以提到适合于口服、肠胃道外或鼻用药的那些药物组合物，它们是片剂或锭剂、舌下片剂、明胶胶囊、栓剂、霜剂、软膏、皮肤用凝胶等。
采用的剂量可以根据病况的性质与严重程度、用药方式和患者的年龄和体重进行改变。
在本发明的组合物中，活性组分的量是1-300mg化合物A，10-600mg氯吡格雷。
因此，本发明的组合物可以用于治疗涉及TP受体活化的心血管疾病，也用于治疗所述疾病的后果。所述病状包括、但不限于急性冠状动脉综合征、稳定型或非稳定型心绞痛、内皮机能不良、与动脉粥样硬化相关的血管疾病、高血压、糖尿病和心力衰竭，还用于预防和治疗血管、心血管或神经血管系统疾病，特别是与动脉粥样硬化、心房纤颤相关的血栓栓塞疾病以及与心脏病学、神经病学、血管病理学和放射学中的侵入性外科手术(血管成形术、安装支架、分流术、导管等)相关的血栓栓塞疾病。
对胶原蛋白诱发的血小板凝集的抑制作用
使18位志愿者每天口服10mg化合物A与75mg氯吡格雷，连续三天，这些志愿者已用75mg氯吡格雷治疗7天。将化合物A和氯吡格雷组合产品治疗效果与分别服用化合物A与氯吡格雷的效果进行比较。
在试验过程中，使用血小板凝集测量仪测量血小板在富含柠檬酸血小板的血浆(PRPc)上的凝集，计算出离体胶原蛋白(5μg/ml)诱发血小板凝集的抑制百分数。
得到的结果如下：
-服用化合物A本身达到35％抑制，
-服用氯吡格雷本身达到11％抑制，
-服用化合物A与氯吡格雷的组合产品达到62％抑制。
这些结果非常清楚地表明，服用这两种化合物的组合产品对胶原蛋白诱发血小板凝集具有协同作用。由这种组合产品产生的抗聚集作用高于分别服用两种产品的效果之和。在已有文献中从未提及该种作用。
上述结果表明，这种组合产品可以有效治疗需要提高与血管作用相关的抗血栓形成作用的急性或慢性病况(神经血管或心血管疾病的急性治疗或二次预防)。

Claims (11)

1、任选呈光学异构体形式的下式(I)化合物(A)或其一种药学上可接受盐与氯吡格雷或其一种药学上可接受盐的组合产品：
Figure A2004800283560002C1
2、根据权利要求1所述的组合产品，其特征在于化合物(A)呈(R)构型的光学异构体形式。
3、根据权利要求1或2所述的组合产品，其特征在于化合物(A)呈钠盐形式。
4、根据权利要求1、2和3中任一项权利要求所述的组合产品，其特征在于氯吡格雷呈硫酸氢盐形式。
5、药物组合物，该药物组合物含有任选呈光学异构体形式的化合物(A)或其一种药学上可接受盐与氯吡格雷或其一种药学上可接受盐的组合产品作为活性组分，并且还含有一种或多种药学上可接受的惰性赋形剂或载体。
6、根据权利要求5所述的药物组合物，其特征在于化合物(A)呈(R)构型光学异构体形式。
7、根据权利要求5或6所述的药物组合物，其特征在于化合物(A)呈钠盐形式。
8、根据权利要求5、6和7中任一项权利要求所述的药物组合物，其特征在于氯吡格雷呈硫酸氢盐形式。
9、根据权利要求5-8中任一项权利要求所述的药物组合物，其特征在于活性组分的量分别是1-300mg化合物A，10-600mg氯吡格雷。
10、根据权利要求5-9中任一项权利要求所述的药物组合物，该药物组合物用于治疗涉及TP受体活化的心血管疾病，也用于治疗所述疾病的后果。
11、根据权利要求10所述的药物组合物，该药物组合物用于治疗急性冠状动脉综合征、稳定型或非稳定型心绞痛、内皮机能不良、与动脉粥样硬化相关的血管疾病、高血压、糖尿病和心力衰竭，还用于预防和治疗血管、心血管或神经血管系统疾病，特别是与动脉粥样硬化、心房纤颤相关的血栓栓塞疾病以及与心脏病学、神经病学、血管病理学和放射学中的侵入性外科手术相关的血栓栓塞疾病。
CNB2004800283560A 2003-10-03 2004-10-01 抗动脉粥样血栓形成剂与抗血小板凝集剂的新组合产品 Expired - Fee Related CN100453075C (zh)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
FR0311595 2003-10-03
FR0311595A FR2860436B1 (fr) 2003-10-03 2003-10-03 Nouvelle association d'un anti-atherothrombotique et d'un antiagregant plaquettaire

Publications (2)

Publication Number Publication Date
CN1859902A true CN1859902A (zh) 2006-11-08
CN100453075C CN100453075C (zh) 2009-01-21

Family

ID=34307392

Family Applications (1)

Application Number Title Priority Date Filing Date
CNB2004800283560A Expired - Fee Related CN100453075C (zh) 2003-10-03 2004-10-01 抗动脉粥样血栓形成剂与抗血小板凝集剂的新组合产品

Country Status (28)

Country Link
US (2) US20070054934A1 (zh)
EP (1) EP1677779B1 (zh)
JP (1) JP2007507475A (zh)
KR (1) KR100782246B1 (zh)
CN (1) CN100453075C (zh)
AR (1) AR046043A1 (zh)
AT (1) ATE409033T1 (zh)
AU (1) AU2004277734B2 (zh)
BR (1) BRPI0415043A (zh)
CA (1) CA2540062A1 (zh)
CY (1) CY1108388T1 (zh)
DE (1) DE602004016762D1 (zh)
DK (1) DK1677779T3 (zh)
EA (1) EA009418B1 (zh)
ES (1) ES2314457T3 (zh)
FR (1) FR2860436B1 (zh)
GE (1) GEP20084546B (zh)
HR (1) HRP20080546T3 (zh)
MA (1) MA28081A1 (zh)
MX (1) MXPA06003713A (zh)
MY (1) MY137953A (zh)
NO (1) NO20061944L (zh)
NZ (1) NZ545988A (zh)
PL (1) PL1677779T3 (zh)
PT (1) PT1677779E (zh)
SI (1) SI1677779T1 (zh)
UA (1) UA80220C2 (zh)
WO (1) WO2005032533A1 (zh)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
MXPA05014086A (es) * 2005-12-20 2007-06-20 Leopoldo De Jesus Espinosa Abdala Composiciones farmaceuticas que comprenden sustancias antiagregantes plaquetarios combinadas para su uso en el tratamiento y prevencion de eventos vasculares de origen isquemico.
FR2899473B1 (fr) * 2006-04-07 2008-06-13 Servier Lab Utilisation d'un compose anti-atherothrombotique pour l'obtention de medicaments destines au traitement des troubles vasculaires
EA020531B1 (ru) * 2007-04-13 2014-11-28 Милленниум Фармасьютикалз, Инк. КОМБИНИРОВАННАЯ ТЕРАПИЯ АНТИКОАГУЛИРУЮЩЕГО СРЕДСТВА С СОЕДИНЕНИЕМ, КОТОРОЕ ДЕЙСТВУЕТ КАК ИНГИБИТОР ФАКТОРА Ха
FR2920772B1 (fr) * 2007-09-11 2009-10-23 Servier Lab Association entre un anti-atherothrombotique et un inhibiteur de l'enzyme de conversion de l'angiotensine

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2711139B1 (fr) * 1993-10-15 1995-12-01 Adir Nouveaux dérivés de 1,2,3,4-tétrahydronaphtalène, leur procédé de préparation et les compositions pharmaceutiques qui les contiennent.
US6509348B1 (en) * 1998-11-03 2003-01-21 Bristol-Myers Squibb Company Combination of an ADP-receptor blocking antiplatelet drug and a thromboxane A2 receptor antagonist and a method for inhibiting thrombus formation employing such combination

Also Published As

Publication number Publication date
KR100782246B1 (ko) 2007-12-05
KR20060061399A (ko) 2006-06-07
AR046043A1 (es) 2005-11-23
CA2540062A1 (fr) 2005-04-14
EP1677779B1 (fr) 2008-09-24
CN100453075C (zh) 2009-01-21
ES2314457T3 (es) 2009-03-16
GEP20084546B (en) 2008-11-25
BRPI0415043A (pt) 2006-12-12
US20100056564A1 (en) 2010-03-04
DE602004016762D1 (de) 2008-11-06
CY1108388T1 (el) 2014-02-12
MY137953A (en) 2009-04-30
NZ545988A (en) 2008-11-28
FR2860436B1 (fr) 2006-01-20
WO2005032533A1 (fr) 2005-04-14
EA200600657A1 (ru) 2006-08-25
UA80220C2 (en) 2007-08-27
AU2004277734B2 (en) 2007-05-24
EA009418B1 (ru) 2007-12-28
US20070054934A1 (en) 2007-03-08
HK1093900A1 (zh) 2007-03-16
JP2007507475A (ja) 2007-03-29
SI1677779T1 (sl) 2009-02-28
PT1677779E (pt) 2008-10-23
NO20061944L (no) 2006-05-02
AU2004277734A1 (en) 2005-04-14
EP1677779A1 (fr) 2006-07-12
MA28081A1 (fr) 2006-08-01
HRP20080546T3 (hr) 2009-01-31
AU2004277734B8 (en) 2005-04-14
PL1677779T3 (pl) 2009-02-27
DK1677779T3 (da) 2009-01-05
MXPA06003713A (es) 2006-06-14
FR2860436A1 (fr) 2005-04-08
ATE409033T1 (de) 2008-10-15

Similar Documents

Publication Publication Date Title
JP2009504737A (ja) 脈管疾患の治療又は予防のためのｐａｒ−１／ｐａｒ−４阻害剤の使用
HUP0203585A2 (hu) Gyógyszerkombinációk
BRPI0620641A2 (pt) usos de compostos antagonistas de receptor de trombina na profilaxia de complicações de cirurgia cardiopulmonar
CN100453075C (zh) 抗动脉粥样血栓形成剂与抗血小板凝集剂的新组合产品
US20060160793A1 (en) Use of meloxicam in combination with an antiplatelet agent for treatment of acute coronary syndrome and related conditions
JP6840197B2 (ja) 虚血性事象を処置し、その発生率を低減させ、かつ／または予防する方法
CN1297265C (zh) 抗血栓形成药与阿司匹林的新组合及其在制备用于治疗动脉粥样硬化血栓形成性疾病的药物中的用途
NZ525487A (en) Use of melagatran for manufacture of a medicament for the treatment of ischemic disorders
HK1093900B (zh) 抗动脉粥样血栓形成剂与抗血小板凝集剂的新组合产品
Nizankowska et al. Salicylate pre‐treatment attenuates intensity of bronchial and nasal symptoms precipitated by aspirin in aspirin‐intolerant patients
JP2005528376A5 (zh)
WO2016181135A1 (en) The use of acetazolamide and methazolamide for the control and monitoring of thrombosis and clotting
JP2004189711A (ja) 急性冠動脈症候群および関連病態の治療のための抗血小板薬と組合せたメロキシカムの使用
CN101693025A (zh) 抗动脉粥样硬化血栓形成的化合物在制备用于治疗血管障碍的药物中的用途
TW200409638A (en) Use of MELOXICAM in combination with an antiplatelet agent for treatment of acute coronary syndrome and related conditions
HK1114771A (zh) 抗动脉粥样化血栓形成的化合物在获得用於治疗血管疾病的药物中的用途

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
REG Reference to a national code

Ref country code: HK

Ref legal event code: DE

Ref document number: 1093900

Country of ref document: HK

C14 Grant of patent or utility model
GR01 Patent grant
REG Reference to a national code

Ref country code: HK

Ref legal event code: GR

Ref document number: 1093900

Country of ref document: HK

C17 Cessation of patent right
CF01 Termination of patent right due to non-payment of annual fee

Granted publication date: 20090121

Termination date: 20101001