[go: up one dir, main page]

CN100404512C - 盐酸伊伐布雷定的βd-晶形、其制备方法和含有它的药物组合物 - Google Patents

盐酸伊伐布雷定的βd-晶形、其制备方法和含有它的药物组合物 Download PDF

Info

Publication number
CN100404512C
CN100404512C CNB2006100580746A CN200610058074A CN100404512C CN 100404512 C CN100404512 C CN 100404512C CN B2006100580746 A CNB2006100580746 A CN B2006100580746A CN 200610058074 A CN200610058074 A CN 200610058074A CN 100404512 C CN100404512 C CN 100404512C
Authority
CN
China
Prior art keywords
hydrochloric acid
crystalline form
acid ivabradine
ivabradine
spectral line
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.)
Active
Application number
CNB2006100580746A
Other languages
English (en)
Other versions
CN1827599A (zh
Inventor
S·霍瓦特
M-N·奥古斯特
G·达米安
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.)
Laboratoires Servier SAS
Original Assignee
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
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=34954878&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=CN100404512(C) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Laboratoires Servier SAS filed Critical Laboratoires Servier SAS
Publication of CN1827599A publication Critical patent/CN1827599A/zh
Application granted granted Critical
Publication of CN100404512C publication Critical patent/CN100404512C/zh
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
    • C07D223/14—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
    • C07D223/16—Benzazepines; Hydrogenated benzazepines
    • 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
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • 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
    • A61P9/06—Antiarrhythmics
    • 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
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J23/00—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00
    • B01J23/38—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00 of noble metals
    • B01J23/48—Silver or gold
    • B01J23/50—Silver
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J23/00—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00
    • B01J23/38—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00 of noble metals
    • B01J23/54—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00 of noble metals combined with metals, oxides or hydroxides provided for in groups B01J23/02 - B01J23/36
    • B01J23/56—Platinum group metals
    • B01J23/62—Platinum group metals with gallium, indium, thallium, germanium, tin or lead
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J23/00—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00
    • B01J23/38—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00 of noble metals
    • B01J23/54—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00 of noble metals combined with metals, oxides or hydroxides provided for in groups B01J23/02 - B01J23/36
    • B01J23/56—Platinum group metals
    • B01J23/62—Platinum group metals with gallium, indium, thallium, germanium, tin or lead
    • B01J23/622—Platinum group metals with gallium, indium, thallium, germanium, tin or lead with germanium, tin or lead
    • B01J23/626—Platinum group metals with gallium, indium, thallium, germanium, tin or lead with germanium, tin or lead with tin
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J23/00—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00
    • B01J23/70—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00 of the iron group metals or copper
    • B01J23/89—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00 of the iron group metals or copper combined with noble metals
    • B01J23/892—Nickel and noble metals
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J35/00—Catalysts, in general, characterised by their form or physical properties
    • B01J35/20—Catalysts, in general, characterised by their form or physical properties characterised by their non-solid state
    • B01J35/23—Catalysts, in general, characterised by their form or physical properties characterised by their non-solid state in a colloidal state
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J37/00—Processes, in general, for preparing catalysts; Processes, in general, for activation of catalysts
    • B01J37/02—Impregnation, coating or precipitation
    • B01J37/0201—Impregnation
    • B01J37/0211—Impregnation using a colloidal suspension
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J37/00—Processes, in general, for preparing catalysts; Processes, in general, for activation of catalysts
    • B01J37/02—Impregnation, coating or precipitation
    • B01J37/0201—Impregnation
    • B01J37/0213—Preparation of the impregnating solution
    • C—CHEMISTRY; METALLURGY
    • C10—PETROLEUM, GAS OR COKE INDUSTRIES; TECHNICAL GASES CONTAINING CARBON MONOXIDE; FUELS; LUBRICANTS; PEAT
    • C10G—CRACKING HYDROCARBON OILS; PRODUCTION OF LIQUID HYDROCARBON MIXTURES, e.g. BY DESTRUCTIVE HYDROGENATION, OLIGOMERISATION, POLYMERISATION; RECOVERY OF HYDROCARBON OILS FROM OIL-SHALE, OIL-SAND, OR GASES; REFINING MIXTURES MAINLY CONSISTING OF HYDROCARBONS; REFORMING OF NAPHTHA; MINERAL WAXES
    • C10G45/00—Refining of hydrocarbon oils using hydrogen or hydrogen-generating compounds
    • C10G45/32—Selective hydrogenation of the diolefin or acetylene compounds
    • C10G45/34—Selective hydrogenation of the diolefin or acetylene compounds characterised by the catalyst used
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J21/00—Catalysts comprising the elements, oxides, or hydroxides of magnesium, boron, aluminium, carbon, silicon, titanium, zirconium, or hafnium
    • B01J21/02—Boron or aluminium; Oxides or hydroxides thereof
    • B01J21/04—Alumina
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J23/00—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00
    • B01J23/38—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00 of noble metals
    • B01J23/54—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00 of noble metals combined with metals, oxides or hydroxides provided for in groups B01J23/02 - B01J23/36
    • B01J23/56—Platinum group metals
    • B01J23/62—Platinum group metals with gallium, indium, thallium, germanium, tin or lead
    • B01J23/622—Platinum group metals with gallium, indium, thallium, germanium, tin or lead with germanium, tin or lead
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J23/00—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00
    • B01J23/70—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00 of the iron group metals or copper
    • B01J23/89—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00 of the iron group metals or copper combined with noble metals
    • B01J23/8926—Copper and noble metals
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J35/00—Catalysts, in general, characterised by their form or physical properties
    • B01J35/30—Catalysts, in general, characterised by their form or physical properties characterised by their physical properties
    • B01J35/391—Physical properties of the active metal ingredient
    • B01J35/393—Metal or metal oxide crystallite size
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J35/00—Catalysts, in general, characterised by their form or physical properties
    • B01J35/30—Catalysts, in general, characterised by their form or physical properties characterised by their physical properties
    • B01J35/396—Distribution of the active metal ingredient
    • B01J35/397—Egg shell like
    • 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
    • C07B2200/13—Crystalline forms, e.g. polymorphs

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Materials Engineering (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Epidemiology (AREA)
  • Urology & Nephrology (AREA)
  • Hospice & Palliative Care (AREA)
  • Vascular Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Other In-Based Heterocyclic Compounds (AREA)
  • Saccharide Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Hydrogenated Pyridines (AREA)
  • Medicinal Preparation (AREA)
  • Steroid Compounds (AREA)

Abstract

通式(I)的盐酸伊伐布雷定的βd-晶形：其特征在于其粉末X射线衍射图。药物。

Description

盐酸伊伐布雷定的βd-晶形、其制备方法和含有它的药物组合物
本发明涉及通式(I)的盐酸伊伐布雷定(ivabradine hydrochloride)的新βd-晶形、其制备方法和含有它的药物组合物：
Figure C20061005807400041
伊伐布雷定及其与药学上可接受的酸形成的加成盐、更具体为其盐酸盐具有极为有价值的药理和治疗特性，尤其是减慢心律(bradycardic)特性，从而使得这些化合物可用于治疗或预防心肌缺血的各种临床情况如心绞痛、心肌梗死和相关节律失常，以及涉及节律失常的各种病理情况、尤其是室上性节律失常，和心力衰竭。
欧洲专利说明书EP 0534 859中已经描述了伊伐布雷定及其与药学上可接受的酸形成的加成盐、更尤其是其盐酸盐的制备和治疗用途。
鉴于该化合物的药物价值，所以最重要的是获得具有极佳纯度的该化合物。另外重要的是能够通过一种易于转化成工业化规模的方法合成它，尤其是允许快速过滤和干燥的形式。最终，该晶形必须完全可再现、易于配制且足够稳定以便其长期贮存，而对温度、光或氧的水平没有特定的要求。
专利说明书EP 0534 859中描述了用于合成伊伐布雷定及其盐酸盐的方法。然而，该对比文献中未特别详述用于以可再现方式获得表现出那些特征的伊伐布雷定形式的条件。
本申请人目前已经发现，可以获得伊伐布雷定的特定盐即盐酸盐的一种晶体形式，该晶形得到充分定义并且表现出有价值的稳定性和加工性能的特征。
更具体而言，本发明涉及盐酸伊伐布雷定的βd-晶形，其特征在于如下粉末X射线衍射图，所述衍射图使用PANalytical X’Pert Pro衍射仪与X’Celerator检测器测定，并根据谱线(ray)位置(布拉格角2θ，以度表示)、谱线高度(以计数表示)、谱线面积(以计数×度表示)、半高处的谱线宽度(“FWHM”，以度表示)和晶面间距d(以表示)表示：
Figure C20061005807400052
本发明还涉及制备盐酸伊伐布雷定的βd-晶形的方法，该方法的特征在于将盐酸伊伐布雷定和水的混合物或盐酸伊伐布雷定、异丙醇和水的混合物加热，直至溶解完全，然后逐步冷却，直至结晶完全，并且收集由此形成的晶体并脱水。
·在本发明的结晶方法中，能够使用通过任意方法获得的盐酸伊伐布雷定，例如通过专利说明书EP 0534 859中所述的制备方法获得的盐酸伊伐布雷定。
·可以在冷却步骤中有利地将该溶液种晶。
本发明还涉及药物组合物，包含作为活性成分的盐酸伊伐布雷定的βd-晶形以及一种或多种适宜的惰性无毒性赋形剂。在本发明的药物组合物中，更尤其可以提及的是适合于口服、胃肠外(静脉内或皮下)或鼻部给药的那些片剂或糖衣丸、舌下片、明胶胶囊、锭剂、栓剂、霜剂、软膏剂、皮肤凝胶、可注射制剂、可饮用的混悬液。
有用的剂量可以根据疾病的性质和严重程度、给药途径和患者的年龄和体重而改变。该剂量在1-500mg/天之间改变，分一次或多次给药。
下列实施例解释本发明。
在下列实验条件下测定X射线粉末衍射光谱：
-PANalytical X’Pert Pro衍射仪、X’Celerator检测器、温控室；
-电压45kV，电流40mA；
-上机(mounting)θ-θ；
-镍(Kβ)滤波器；
-入射线和衍射线索勒缝隙：0.04拉德；
-发散狭缝的固定角：1/8°；
-障板(mask)：10mm；
-防散射狭缝：1/4°；
-测定方式：从3°连续至30°，按0.017°递增；
-测定时间/步骤：19.7s；
-总时间：4min 32s
-测定速度：0.108°/s；
-测定温度：环境。
实施例1：盐酸伊伐布雷定的βd-晶形
将720ml纯化水预加热至50℃，然后分批加入按照专利说明书EP 0534859中所述方法获得的250g盐酸伊伐布雷定，同时搅拌，并且将该混合物在74℃加热，直至溶解完全。将所得澄清溶液在74℃再加热2小时，然后逐步冷却，首先冷却至40℃，然后冷却至环境温度。随后将该溶液在环境温度下贮存2天，然后使固体混悬液在结晶板上以薄层展开。在适度氮气流中驱散过量的水。
通过以5℃/分钟的速率逐步加热至达80℃的温度，使由此获得的产物脱水。
X射线粉末衍射图：
通过下表中整理的重要谱线，给出了盐酸伊伐布雷定βd-晶形的X射线粉末衍射图谱(衍射角)：
Figure C20061005807400081
实施例2：药物组合物
制备1000片各自含有5mg伊伐布雷定碱的片剂的配方：
实施例1的化合物                5.39g
玉米淀粉                       20g
无水胶体二氧化硅               0.2g
甘露糖醇                       63.91g
PVP                            10g
硬脂酸镁                       0.5g

Claims (8)

1.通式(I)的盐酸伊伐布雷定的βd-晶形：
Figure C2006100580740002C1
其特征在于如下粉末X射线衍射图，所述衍射图使用PANalytical X’PertPro衍射仪与X’Celerator检测器测定，并根据谱线位置、谱线高度、谱线面积、半高处的谱线宽度和晶面间距d表示：
Figure C2006100580740002C2
其中所述的谱线位置以布拉格角2θ表示，单位为度，所述的谱线高度以计数表示，所述的谱线面积以计数×度表示，所述的半高处的谱线宽度以度表示，所述的晶面间距d以表示。
2.制备根据权利要求1的盐酸伊伐布雷定的βd-晶形的方法，其特征在于将盐酸伊伐布雷定和水的混合物或盐酸伊伐布雷定、异丙醇和水的混合物加热，直至溶解完全，然后逐步冷却，直至结晶完全，并且收集由此形成的晶体，然后脱水。
3.根据权利要求2的方法，其特征在于在冷却步骤中将盐酸伊伐布雷定的溶液种晶。
4.药物组合物，包含作为活性成分的根据权利要求1的盐酸伊伐布雷定的βd-晶形以及一种或多种药学上可接受的惰性无毒性载体。
5.根据权利要求1的盐酸伊伐布雷定的βd-晶形在制备可用作减慢心率药的药物中的用途。
6.根据权利要求1的盐酸伊伐布雷定的βd-晶形在制备药物中的用途，所述药物可用于治疗或预防心肌缺血的各种临床情况以及涉及节律失常的各种病理情况和心力衰竭。
7.根据权利要求6的用途，其中所述的心肌缺血的临床情况是心绞痛、心肌梗死或相关节律失常。
8.根据权利要求6的用途，其中所述的涉及节律失常的病理情况是室上性节律失常。
CNB2006100580746A 2005-02-28 2006-02-28 盐酸伊伐布雷定的βd-晶形、其制备方法和含有它的药物组合物 Active CN100404512C (zh)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
FR0501987 2005-02-28
FR0501987A FR2882554B1 (fr) 2005-02-28 2005-02-28 Forme critalline beta d du chlorhydrate de l'ivabradine, son procede de preparation, et les compositions pharmaceutiques qui la contiennent

Publications (2)

Publication Number Publication Date
CN1827599A CN1827599A (zh) 2006-09-06
CN100404512C true CN100404512C (zh) 2008-07-23

Family

ID=34954878

Family Applications (1)

Application Number Title Priority Date Filing Date
CNB2006100580746A Active CN100404512C (zh) 2005-02-28 2006-02-28 盐酸伊伐布雷定的βd-晶形、其制备方法和含有它的药物组合物

Country Status (41)

Country Link
US (3) US7361652B2 (zh)
EP (1) EP1695710B1 (zh)
JP (1) JP4628973B2 (zh)
KR (1) KR100835446B1 (zh)
CN (1) CN100404512C (zh)
AP (1) AP2190A (zh)
AR (1) AR052925A1 (zh)
AT (1) ATE397449T1 (zh)
BR (1) BRPI0600795B8 (zh)
CA (1) CA2537420C (zh)
CO (1) CO5770098A1 (zh)
CR (1) CR8247A (zh)
CY (1) CY1109011T1 (zh)
DE (1) DE602006001365D1 (zh)
DK (1) DK1695710T3 (zh)
EA (1) EA008466B1 (zh)
EC (1) ECSP066374A (zh)
ES (1) ES2308690T3 (zh)
FR (1) FR2882554B1 (zh)
GE (1) GEP20084466B (zh)
GT (1) GT200600085A (zh)
HK (1) HK1096388A1 (zh)
HR (1) HRP20080418T5 (zh)
IL (1) IL173958A0 (zh)
JO (1) JO2516B1 (zh)
MA (1) MA28133A1 (zh)
MY (1) MY158127A (zh)
NO (1) NO338369B1 (zh)
NZ (1) NZ545577A (zh)
PE (1) PE20061091A1 (zh)
PL (1) PL1695710T3 (zh)
PT (1) PT1695710E (zh)
RS (1) RS50599B (zh)
SA (1) SA06270039B1 (zh)
SG (1) SG125230A1 (zh)
SI (1) SI1695710T1 (zh)
TW (1) TWI315306B (zh)
UA (1) UA80903C2 (zh)
UY (1) UY29404A1 (zh)
WO (1) WO2006092491A1 (zh)
ZA (1) ZA200601761B (zh)

Families Citing this family (35)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR100870174B1 (ko) * 2003-12-04 2008-11-24 바이엘 크롭사이언스 아게 살충 및 살비성을 가지는 활성 물질 배합물
FR2868777B1 (fr) * 2004-04-13 2006-05-26 Servier Lab Nouveau procede de synthese de l'ivabradine et de ses sels d'addition a un acide pharmaceutiquement acceptable
FR2882555B1 (fr) * 2005-02-28 2007-05-04 Servier Lab Forme cristalline gamma du chlorhydrate de l'ivabradine, son procede de preparation, et les compositions pharmaceutiques qui la contiennent
FR2882553B1 (fr) * 2005-02-28 2007-05-04 Servier Lab Forme cristalline beta du chlorhydrate de l'ivabradine, son procede de preparation, et les compositions pharmaceutiques qui la contiennent
FR2882556B1 (fr) * 2005-02-28 2007-05-04 Servier Lab Forme cristalline gamma d du chlorhydrate de l'ivabradine, son procede de preparation, et les compositions pharmaceutiques qui la contiennent
FR2882554B1 (fr) * 2005-02-28 2007-05-04 Servier Lab Forme critalline beta d du chlorhydrate de l'ivabradine, son procede de preparation, et les compositions pharmaceutiques qui la contiennent
FR2891826B1 (fr) * 2005-10-11 2007-12-28 Servier Lab Forme cristalline 6 du chlorhydrate de l'ivabradine, son procede de preparation et les compositions pharmaceutiques qui la contiennent
FR2891827B1 (fr) * 2005-10-11 2007-12-28 Servier Lab Forme cristalline deltad du chlorhydrate de l'ivabradine, son procede de preparation, et les compositions pharmaceutiques qui la contiennent
FR2894825B1 (fr) * 2005-12-21 2010-12-03 Servier Lab Nouvelle association d'un inhibiteur du courant if sinusal et d'un inhibiteur de l'enzyme de conversion et les compositions pharmaceutiques qui la contiennent
WO2008065681A2 (en) 2006-11-30 2008-06-05 Cadila Healthcare Limited Process for preparation of ivabradine hydrochloride
CN101353325B (zh) * 2007-07-27 2011-11-09 上海优拓医药科技有限公司 稳定型盐酸伊伐布雷定结晶及其制备方法
ES2528026T3 (es) 2007-05-30 2015-02-03 Ind-Swift Laboratories Limited Sales de oxalato de ivabridina cristalino y polimorfos de los mismos
FR2920773B1 (fr) * 2007-09-11 2009-10-23 Servier Lab Derives de 1,2,4,5-tetrahydro-3h-benzazepines, leur procede de preparation et les compositions pharmaceutiques qui les contiennent
EP2367782B1 (en) 2008-12-22 2013-02-13 KRKA, D.D., Novo Mesto Process for preparation of ivabradine
CN101774969B (zh) 2009-01-13 2012-07-04 江苏恒瑞医药股份有限公司 硫酸伊伐布雷定及其i型结晶的制备方法
EA201290772A1 (ru) 2010-02-12 2013-02-28 КРКА, д.д., НОВО МЕСТО Новые формы ивабрадина гидрохлорида
HUP1000245A2 (en) 2010-05-07 2011-11-28 Richter Gedeon Nyrt Industrial process for the production ivabradin salts
EP2579860B1 (en) 2010-06-14 2014-04-23 Ratiopharm GmbH Ivabradine-containing pharmaceutical composition with modified release
WO2012025940A1 (en) 2010-08-25 2012-03-01 Cadila Healthcare Limited Polymorphic form of ivabradine hydrochloride and process for preparation thereof
EP2726462B1 (en) 2011-08-02 2017-03-22 Sandoz AG Acetone solvate of ivabradine hydrochloride
EP2589594A1 (en) 2011-11-04 2013-05-08 Urquima S.A. Ivabradine hydrochloride Form IV
WO2013064427A1 (en) 2011-11-04 2013-05-10 Synthon Bv A process for making crystalline delta-form of ivabradine hydrochloride
WO2013102919A1 (en) 2011-11-14 2013-07-11 Cadila Healthcare Limited Polymorphic forms of ivabradine hydrochloride
EP2948432B1 (en) 2013-01-24 2018-09-19 Synthon BV Process for making ivabradine
CZ305096B6 (cs) 2013-10-02 2015-04-29 Zentiva, K.S. Pevná forma Ivabradin hydrochloridu a (S)-mandlové kyseliny a její farmaceutická kompozice
MX363389B (es) 2013-12-12 2019-03-20 Synthon Bv Composicion farmaceutica que comprende ivabradina amorfa.
PT2774606T (pt) 2014-02-14 2019-05-06 Synthon Bv Composição farmacêutica compreendendo polimorfo de cloridrato de ivabradina iv
CZ305436B6 (cs) 2014-07-10 2015-09-16 Zentiva, K.S. Pevná forma Ivabradin hydrochloridu a (R)-mandlové kyseliny a její farmaceutická kompozice
CN107056706B (zh) * 2015-12-21 2020-05-05 江苏恒瑞医药股份有限公司 一种用于制备盐酸伊伐布雷定α晶型的方法
TR201703066A2 (tr) 2017-02-28 2018-09-21 Sanovel Ilac Sanayi Ve Ticaret Anonim Sirketi İvabradi̇ni̇n kati oral farmasöti̇k kompozi̇syonlari
EP3366282A1 (en) 2017-02-28 2018-08-29 Sanovel Ilac Sanayi ve Ticaret A.S. Solid oral pharmaceutical compositions of ivabradine
JP7132757B2 (ja) 2018-06-12 2022-09-07 プレス工業株式会社 スライド窓保持装置
IT202000025312A1 (it) 2020-10-26 2022-04-26 Cambrex Profarmaco Milano S R L Processi per la preparazione di polimorfi di ivabradina hcl
IT202100019967A1 (it) 2021-07-27 2023-01-27 Campagnolo Srl Dispositivo manuale di comando per bicicletta
IT202100019988A1 (it) 2021-07-27 2023-01-27 Campagnolo Srl Dispositivo manuale di comando per bicicletta

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5296482A (en) * 1991-09-27 1994-03-22 Adir Et Compagnie (Benzocycloalkyl) alkylamines

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3119874A1 (de) * 1981-05-19 1982-12-09 Dr. Karl Thomae Gmbh, 7950 Biberach "benzazepinderivate, ihre herstellung und ihre verwendung als arzneimittel"
DE3418270A1 (de) * 1984-05-17 1985-11-21 Dr. Karl Thomae Gmbh, 7950 Biberach Neue aminotetralinderivate, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung
FR2868777B1 (fr) * 2004-04-13 2006-05-26 Servier Lab Nouveau procede de synthese de l'ivabradine et de ses sels d'addition a un acide pharmaceutiquement acceptable
FR2882556B1 (fr) * 2005-02-28 2007-05-04 Servier Lab Forme cristalline gamma d du chlorhydrate de l'ivabradine, son procede de preparation, et les compositions pharmaceutiques qui la contiennent
FR2882554B1 (fr) * 2005-02-28 2007-05-04 Servier Lab Forme critalline beta d du chlorhydrate de l'ivabradine, son procede de preparation, et les compositions pharmaceutiques qui la contiennent
FR2882555B1 (fr) * 2005-02-28 2007-05-04 Servier Lab Forme cristalline gamma du chlorhydrate de l'ivabradine, son procede de preparation, et les compositions pharmaceutiques qui la contiennent
FR2882553B1 (fr) * 2005-02-28 2007-05-04 Servier Lab Forme cristalline beta du chlorhydrate de l'ivabradine, son procede de preparation, et les compositions pharmaceutiques qui la contiennent
FR2891827B1 (fr) * 2005-10-11 2007-12-28 Servier Lab Forme cristalline deltad du chlorhydrate de l'ivabradine, son procede de preparation, et les compositions pharmaceutiques qui la contiennent
FR2891826B1 (fr) * 2005-10-11 2007-12-28 Servier Lab Forme cristalline 6 du chlorhydrate de l'ivabradine, son procede de preparation et les compositions pharmaceutiques qui la contiennent

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5296482A (en) * 1991-09-27 1994-03-22 Adir Et Compagnie (Benzocycloalkyl) alkylamines

Also Published As

Publication number Publication date
CY1109011T1 (el) 2014-07-02
PL1695710T3 (pl) 2008-09-30
UY29404A1 (es) 2006-07-31
US20060194965A1 (en) 2006-08-31
AU2006200854A1 (en) 2006-09-14
EA008466B1 (ru) 2007-06-29
US20090318416A1 (en) 2009-12-24
AP2190A (en) 2010-12-30
JO2516B1 (en) 2010-03-17
BRPI0600795A (pt) 2007-05-08
JP4628973B2 (ja) 2011-02-09
GEP20084466B (en) 2008-08-25
ATE397449T1 (de) 2008-06-15
US7867995B2 (en) 2011-01-11
SI1695710T1 (sl) 2008-10-31
FR2882554B1 (fr) 2007-05-04
CR8247A (es) 2008-10-06
US20080161286A1 (en) 2008-07-03
JP2006241155A (ja) 2006-09-14
HRP20080418T3 (en) 2008-09-30
SA06270039B1 (ar) 2010-03-30
ES2308690T3 (es) 2008-12-01
NO338369B1 (no) 2016-08-15
KR20060095500A (ko) 2006-08-31
US7361652B2 (en) 2008-04-22
MA28133A1 (fr) 2006-09-01
EA200600321A1 (ru) 2006-08-25
HRP20080418T5 (en) 2008-11-30
ECSP066374A (es) 2006-10-17
HK1096388A1 (en) 2007-06-01
CA2537420A1 (fr) 2006-08-28
NO20060947L (no) 2006-08-29
GT200600085A (es) 2006-10-24
DE602006001365D1 (de) 2008-07-17
EP1695710B1 (fr) 2008-06-04
CO5770098A1 (es) 2007-06-29
UA80903C2 (en) 2007-11-12
PE20061091A1 (es) 2006-11-18
IL173958A0 (en) 2006-07-05
MY158127A (en) 2016-08-30
RS50599B (sr) 2010-05-07
WO2006092491A1 (fr) 2006-09-08
BRPI0600795B1 (pt) 2019-02-05
SG125230A1 (en) 2006-09-29
KR100835446B1 (ko) 2008-06-09
TWI315306B (en) 2009-10-01
ZA200601761B (en) 2008-04-30
BRPI0600795B8 (pt) 2021-05-25
NZ545577A (en) 2007-01-26
CN1827599A (zh) 2006-09-06
EP1695710A1 (fr) 2006-08-30
PT1695710E (pt) 2008-07-21
AP2006003520A0 (en) 2006-02-28
CA2537420C (fr) 2010-03-30
AR052925A1 (es) 2007-04-11
FR2882554A1 (fr) 2006-09-01
TW200640874A (en) 2006-12-01
DK1695710T3 (da) 2008-09-22

Similar Documents

Publication Publication Date Title
CN100404512C (zh) 盐酸伊伐布雷定的βd-晶形、其制备方法和含有它的药物组合物
CN1827600B (zh) 盐酸伊伐布雷定的β-晶形、其制备方法和含有它的药物组合物
CN100432057C (zh) 盐酸伊伐布雷定的γd-晶形、其制备方法和含有它的药物组合物
CN100402502C (zh) 盐酸伊伐布雷定的γ-晶形、其制备方法和含有它的药物组合物
TWI377946B (en) Δ-crystalline form of ivabradine hydrochloride, a process for its preparation and pharmaceutical compositions containing it
JP2007112797A (ja) 塩酸イバブラジンのδｄ結晶形態、その製造法、およびそれを含有する医薬組成物
MXPA06002274A (en) Beta-crystalline form of ivabradine hydrochloride, a process for its preparation and pharmaceutical compositions containing it
MXPA06002276A (en) Gamma d-crystalline form of ivabradine hydrochloride, a process for its preparation and pharmaceutical compositions containing it
MXPA06002275A (en) Gamma-crystalline form of ivabradine hydrochloride, a process for its preparation and pharmaceutical compositions containing it

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: 1096388

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: 1096388

Country of ref document: HK