EP1414796A1 - Kristalline formen vi und vii des kalzium atorvastatins - Google Patents
Kristalline formen vi und vii des kalzium atorvastatinsInfo
- Publication number
- EP1414796A1 EP1414796A1 EP02724877A EP02724877A EP1414796A1 EP 1414796 A1 EP1414796 A1 EP 1414796A1 EP 02724877 A EP02724877 A EP 02724877A EP 02724877 A EP02724877 A EP 02724877A EP 1414796 A1 EP1414796 A1 EP 1414796A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- mixture
- water
- atorvastatin calcium
- crystalline form
- hours
- 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.)
- Withdrawn
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/34—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
-
- 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
- A61P3/06—Antihyperlipidemics
Definitions
- the present invention relates to novel crystalline forms of Atorvastatin calcium and to the methods of their production and isolation.
- the present invention relates to novel Forms VI and VII of R-(R * , R * )]-2(4-fluorophenyl)- ⁇ , ⁇ -dihydroxy-5-(l-methylethyl)-3- phenyl-4-[(phenylamino)carbonyl]-l-H-pyrrole-l-heptanoic acid calcium salt and hydrates thereof and to methods of their preparation.
- Atorvastatin is R-(R ⁇ R * )]-2-(4-fluorophenyl)- ⁇ , ⁇ -dihydroxy-5-(l-methylethyl)-3-phenyl-4[(phenylamino)carbonyl]-lH-pyrrole- 1-heptanoic acid.
- Atorvastatin is marketed as the hemi calcium salt trihydrate under the name LIPITOR by Warner Lambert Co and may be represented by Formula 1.
- Atorvastatin is a member of the class of drugs called statins.
- Statin drugs are currently the most therapeutically effective drugs available for reducing low density lipoprotein (LDL) particle concentration in the blood stream of patients at risk for cardiovascular disease.
- LDL low density lipoprotein
- a high level of LDL in to bloodstream has been linked to the formation of coronary lesions, which obstruct the flow of blood and can rupture and promote thrombosis; Goodman Gilman, The Pharmacological Basis of Therapeutics 879 (9 th ed. 1996).
- Reducing plasma LDL levels has been shown to reduce the risk of clinical events in patients with cardiovascular disease and patients who are free of cardiovascular disease but who have hypercholesterolemia; Scandinavian Simvastatin Survival Study Group, 1994; Lipid Research Clinics Program, 1984a, 1984b.
- U.S. Patent 5,929,156 to Warner-Lambert Company discloses crystalline Form I Atorvastatin hydrate, crystalline Form II Atorvastatin and hydrates thereof and crystalline Form IV Atorvastatin and hydrates thereof, which are useful as inhibitors of enzyme 3-hydroxy-3methylglutaryl-coenzyrne A reductase (HMG-CoA reductase) and are hence useful hypolipidemic and hypocholesterolemic agents.
- HMG-CoA reductase 3-hydroxy-3methylglutaryl-coenzyrne A reductase
- U.S. Patent 6,121,461 also to Warner-Lambert Company, discloses crystalline Form III Atorvastatin hydrate, which is also a useful hypolipidemic and hypocholesterolemic agent.
- WO 01/36384 Al to Teva Pharmaceutical Industries Ltd discloses Form V Atorvastatin calcium and hydrates thereof; its preparation and a pharmaceutical composition thereof.
- Atorvastatin is disclosed in U.S. Patent 6,087,511 also to Warner-Lambert Company.
- WO 01/28999 Al to Egis Gyogyszergyarrt discloses a process for the preparation of amorphous Atorvastatin calcium. It is also noteworthy to point out that U.S. Patent No. 5,969,156 designates the Atorvastatin formed by prior art process (viz United States Patents 5,003,080; 5,097,045; 5,103,024; 5,124,482; 5,149,837; 5,155,251 ; 5,216,174; , .
- Atorvastatin is prepared as its calcium salt, which is desirable since it enables Atorvastatin to be conveniently formulated for oral administration. There is hence a need to produce Atorvastatin calcium in a pure and crystalline form to enable formulations to meet exacting pharmaceutical requirements and specifications.
- the process by which the crystalline form of Atorvastatin calcium is produced needs to be one, which is amenable to large-scale production. Additionally, it is desirable that the product should be in a form that is readily filterable and easily dried. Finally, it is economically desirable that the product be stable for extended periods of time without the need for specialized storage conditions.
- the main aspect of the present invention is to provide novel crystalline forms of Atorvastatin calcium and hydrates thereof, and to a method for their preparation.
- Another aspect of the present invention is that, the novel crystalline forms of Atorvastatin calcium and hydrates thereof are obtained in high purity.
- the generally preferred HPLC purity of crystalline Form VI and VII of Atorvastatin calcium and hydrates thereof, of the present invention is greater than 99.0% more preferably greater than 99.5%.
- Most pharmaceutical formulation processes are facilitated by use of the active materials that are free flowing high melting solids.
- the novel crystalline forms of Atorvastatin calcium of the present invention are high melting solids, very suited for formulation.
- the residual solvents associated with the novel forms, Form VI and Form VII are also very well within permissible limits and that again renders the novel crystalline forms suited for formulations.
- the present invention is directed to novel crystalline forms of Atorvastatin calcium and hydrates thereof. These crystalline forms of Atorvastatin calcium are designated as Form VI and Form VII for convenience.
- the present invention further provides a process for the preparation of novel crystalline Form VI and Form VII of Atorvastatin calcium and hydrates thereof, which is a commercially viable process well suited for industrial scale up.
- Fig 1 is a characteristic X ray powder diffractogram of novel crystalline Atorvastatin calcium Form VI.
- Vertical axis Intensity (CPS); Horizontal axis: Two Theta (degrees). The significant d values (A°) obtained are 22.52, 19.44, 11.84, 1 1.23, 9.58, and 4.69.
- Fig 2 is a characteristic is an X ray powder diffractogram of novel crystalline Atorvastatin calcium Form VII.
- Vertical axis Intensity (CPS); Horizontal axis: Two Theta (degrees).
- the significant d values (A°) obtained are 19.36, 11.80 9.60, 4.75, 4.69 and 4.39.
- the crystalline Form VI and Form VII of the present invention may be characterized by their X Ray powder diffraction.
- the X-Ray diffraction patterns of Form VI and VII of Atorvastatin calcium and their hydrates were measured on a Rigaku D/Max 2200 Powder Diffractometer with Cu Radiation source.
- Crystalline Form VI has X-ray powder diffraction pattern essentially as shown in the Table 1. The X-ray powder diffraction pattern is expressed in terms of the 2 ⁇ , d-spacings, and relative intensities > 15 %.
- Table 2 lists the 2 ⁇ , d-spacings, and relative intensities > 15 % for crystalline Form VII of Atorvastatin calcium.
- the present invention is also directed to processes for preparation of novel crystalline forms of Atorvastatin calcium and hydrates thereof.
- the present invention hence, provides a process for the preparation of crystalline Form VI of Atorvastatin calcium, which comprises: a. heating a mixture of [R-(R ⁇ R * )]-2-(4-fluorophenyl)- ⁇ , ⁇ -dihydroxy -5- 1 -methyl ethyl-3-phenyl-4-[(phenyl amino)-carbonyl]-lH-pyrrole- 1-heptanoic acid, tertiary butyl ester (hereinafter referred to as "ester” or "active ingredient” for convenience), acetonitrile and sodium hydroxide flakes to about 25-60°C; b.
- step a) maintaining the reaction mixture of step a) at 25 -60°C for about 3-9 hours preferably 6 hours; c. adding to the above reaction mixture an aqueous solution of calcium acetate hemihydrate; d. further stirring the reaction mixture at 30-50°C for about 30 minutes to 2 hours, preferably 45 minutes; e. filtering the reaction solution obtained in step d) through hyflow bed; f. distilling the solvent from reaction solution of step e) to yield a residue; g.
- step f suspending the residue of step f) in a mixture of aliphatic nitrile solvent selected from acetonitrile and propionitrile; and water, in a ratio of 1 :0.1-2, such that the volume of the mixture of solvent- water is 18-40 times the weight of ester in step a); (The ratio of active ingredient to the mixture of solvent and water is 1 : 18-40 (wt/vol)).
- step g refluxing the reaction mixture obtained in step g) for 10-18 hours preferably 12-14 hours; and i. isolating the crystalline Form VI of Atorvastatin calcium, obtained in step h) by filtration or other conventional methods known in the art.
- step a) of the process an ester with an alkyl group of 1-10 carbon atoms, allyl or benzyl group can be used in place of the tertiary butyl ester and another nitrile such as propionitrile can be used in place of acetonitrile.
- the ratio of solvent to active ingredient in step a) is 16 times the active ingredient (w volume) (gm:ml).
- step a) the molar ratio of active ingredient to base is 1 : 1-1.5 preferably 1 :1.15.
- step a) other alkali hydroxides can be used in place of sodium hydroxide.
- the alkali hydroxides including the sodium hydroxide may be in any form and the form is not limited to flakes.
- Organic salts such as carboxylates and sulphonates.
- the carboxylates may be selected from acetate, propionate, butyrate, tartarate; aryl carboxylates like benzoate and phthlate as well as higher carboxylates like Stearate or dodecanoate. Also included are succinate and ascorborate.
- Sulphonates may be selected from lower alkyl and aryl sulfonates like calcium methane sulfonates, calcium benzene sulfonates and calcium para toluenesulfonates.
- Inorganic salts of calcium may be selected from calcium chloride, fluoride, bromide, iodide and calcium borate and tetra fluoro borate, calcium carbonate, mono, di and tri basic calcium phosphate, calcium sulfate and calcium hydroxide and hydrates thereof.
- the molar ratio of active ingredient to calcium acetate hemihydrate or calcium salt is 1 :0.5-0.7 preferably 1 :0.6.
- the present invention also provides a process for the preparation of crystalline Form VII of Atorvastatin calcium, which comprises: a. suspending residue (prepared as per steps a-f for crystalline form VI) in a mixture of water and organic solvent such as an amide solvent such as dimethyl formamide or an aliphatic nitrile solvent selected from acetonitrile or propionitrile; in a ratio of organic solvent to water 1 :0.1-5 (vol/vol) such that the volume of the mixture of solvent- water is 5 to less than 10 times, the weight of initial ester used in the preparation of crystalline form VI (vol:wt) (ml/gm); b. refluxing the reaction mixture obtained in step a) for 10 minutes to 1 hour preferably 30 minutes; c.
- organic solvent such as an amide solvent such as dimethyl formamide or an aliphatic nitrile solvent selected from acetonitrile or propionitrile
- the organic solvents used in steps c) and d) for the preparation of crystalline Form VII of Atorvastatin calcium include amide solvents such as dimethyl formamide or aliphatic nitrile solvent selected from acetonitrile and propionitrile.
- amide solvents such as dimethyl formamide or aliphatic nitrile solvent selected from acetonitrile and propionitrile.
- the same solvent used in step a) is used in steps c) and d).
- the present invention hence provides novel crystalline forms of Atorvastatin calcium and hydrates thereof, and to a method for their preparation, which is amenable to large-scale production.
- novel crystalline forms of Atorvastatin calcium of the present invention are readily filterable and easily dried. Moreover, the HPLC purity of novel crystalline Form VI and VII of
- Atorvastatin calcium and hydrates thereof, of the present invention is greater than 99.0% more preferably greater than 99.5%.
- the crystalline forms of Atorvastatin calcium of the present invention are also high melting solids with residual solvents within permissible limits and are very well suited for formulation.
- Atorvastatin calcium hydrate may contain 1 to 4 moles of water, preferably 3 moles of water.
- the crystalline Form VI of Atorvastatin calcium hydrate may contain 1 to 5 moles of water, preferably 3 moles of water.
- Example 1 Preparation of crystalline Form VI of Atorvastatin Calcium
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Obesity (AREA)
- Diabetes (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Hematology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pyrrole Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP10010845A EP2292600A1 (de) | 2001-07-30 | 2002-01-07 | Kristalline Formen VI und VII von Atorvastatin Calcium |
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IN620MA2001 | 2001-07-30 | ||
INMA00000620 | 2001-07-30 | ||
PCT/US2002/000431 WO2003011826A1 (en) | 2001-07-30 | 2002-01-07 | Crystalline forms vi and vii of atorvastatin calcium |
Publications (1)
Publication Number | Publication Date |
---|---|
EP1414796A1 true EP1414796A1 (de) | 2004-05-06 |
Family
ID=35160889
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP02724877A Withdrawn EP1414796A1 (de) | 2001-07-30 | 2002-01-07 | Kristalline formen vi und vii des kalzium atorvastatins |
EP10010845A Withdrawn EP2292600A1 (de) | 2001-07-30 | 2002-01-07 | Kristalline Formen VI und VII von Atorvastatin Calcium |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP10010845A Withdrawn EP2292600A1 (de) | 2001-07-30 | 2002-01-07 | Kristalline Formen VI und VII von Atorvastatin Calcium |
Country Status (19)
Country | Link |
---|---|
EP (2) | EP1414796A1 (de) |
JP (1) | JP2005500351A (de) |
KR (1) | KR20040019043A (de) |
CN (1) | CN100471836C (de) |
AU (1) | AU2002255479B2 (de) |
BG (1) | BG108518A (de) |
BR (1) | BR0211488A (de) |
CA (1) | CA2454500C (de) |
CZ (1) | CZ2004126A3 (de) |
EE (1) | EE200400048A (de) |
HR (1) | HRP20040077A2 (de) |
IL (2) | IL159626A0 (de) |
MX (1) | MXPA04000889A (de) |
NO (1) | NO20040390L (de) |
NZ (1) | NZ530785A (de) |
PL (1) | PL368647A1 (de) |
RU (1) | RU2304139C2 (de) |
WO (1) | WO2003011826A1 (de) |
ZA (1) | ZA200400573B (de) |
Families Citing this family (23)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7411075B1 (en) | 2000-11-16 | 2008-08-12 | Teva Pharmaceutical Industries Ltd. | Polymorphic form of atorvastatin calcium |
WO2002041834A2 (en) * | 2000-11-03 | 2002-05-30 | Teva Pharmaceutical Industries, Ltd. | Atorvastatin hemi-calcium form vii |
IL156055A0 (en) | 2000-11-30 | 2003-12-23 | Teva Pharma | Novel crystal forms of atorvastatin hemi calcium and processes for their preparation as well as novel processes for preparing other forms |
US7501450B2 (en) | 2000-11-30 | 2009-03-10 | Teva Pharaceutical Industries Ltd. | Crystal forms of atorvastatin hemi-calcium and processes for their preparation as well as novel processes for preparing other forms |
CA2623600A1 (en) * | 2000-12-27 | 2002-07-04 | Paul Adrian Van Der Schaaf | Crystalline forms of atorvastatin |
AU2003217653A1 (en) * | 2002-02-15 | 2003-09-09 | Teva Pharmaceutical Industries Ltd. | Novel crystal forms of atorvastatin hemi-calcium and processes for their preparation, as well as novel processes for preparing atorvastatin hemi-calcium forms i, viii and ix |
EP1465901A4 (de) | 2002-02-19 | 2006-02-01 | Teva Pharma | Verfahren zur desolvatation von atorvastatin hemi-kalzium solvaten und von im wesentlichen lösungsmittelfreiem atorvastatin hemi-kalzium |
EP1572643A2 (de) * | 2002-11-28 | 2005-09-14 | Teva Pharmaceutical Industries Ltd. | Kristalline form f von atorvastatin hemi calcium salz |
EP1424324A1 (de) * | 2002-11-28 | 2004-06-02 | Teva Pharmaceutical Industries Limited | Kristalline Form F von Atorvastatin |
US20050271717A1 (en) | 2003-06-12 | 2005-12-08 | Alfred Berchielli | Pharmaceutical compositions of atorvastatin |
US7655692B2 (en) | 2003-06-12 | 2010-02-02 | Pfizer Inc. | Process for forming amorphous atorvastatin |
AU2005223491A1 (en) * | 2004-03-17 | 2005-09-29 | Ranbaxy Laboratories Limited | Crystalline form of atorvastatin hemi calcium |
WO2005092852A1 (en) | 2004-03-17 | 2005-10-06 | Ranbaxy Laboratories Limited | Process for the production of atorvastatin calcium in amorphous form |
CA2573969C (en) * | 2004-07-16 | 2014-02-04 | Lek Pharmaceuticals D.D. | Oxidative degradation products of atorvastatin calcium |
CA2701710C (en) | 2004-07-20 | 2013-08-27 | Warner-Lambert Company Llc | Novel forms of [r-(r*,r*)]-2-(4-fluorophenyl)-.beta.,.delta.-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1h-pyrrole-1-heptanoic acid calcium salt (2:1) |
WO2006037125A1 (en) | 2004-09-28 | 2006-04-06 | Teva Pharmaceutical Industries Ltd. | Process for preparing forms of atorvastatin calcium substantially free of impurities |
KR20070067175A (ko) | 2004-10-28 | 2007-06-27 | 워너-램버트 캄파니 엘엘씨 | 무정형 아토르바스타틴 형성 방법 |
WO2006048894A1 (en) * | 2004-11-05 | 2006-05-11 | Morepen Laboratories Limited | Novel crystalline forms of atorvastatin calcium and processes for preparing them. |
CN101370774A (zh) | 2005-12-13 | 2009-02-18 | 特瓦制药工业有限公司 | 阿托伐他汀半钙的晶形及其制备方法 |
US20100260851A1 (en) * | 2007-07-11 | 2010-10-14 | Actavis Group Ptc Ehf | Novel Polymorph of Atorvastatin Calcium and Use Thereof for the Preparation of Amorphous Atorvastatin Calcium |
KR20120011249A (ko) | 2010-07-28 | 2012-02-07 | 주식회사 경보제약 | 아토바스타틴 헤미칼슘염의 신규한 결정형, 이의 수화물, 및 그의 제조방법 |
CN104983702A (zh) * | 2015-07-23 | 2015-10-21 | 青岛蓝盛洋医药生物科技有限责任公司 | 一种治疗高胆固醇血症的药物阿托伐他汀钙组合物片剂 |
CN108157405B (zh) * | 2018-02-06 | 2020-10-02 | 上海应用技术大学 | 一种灭蟑螂饵剂及其制备方法和应用 |
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US5124482A (en) | 1988-02-22 | 1992-06-23 | Warner-Lambert Company | Process for trans-6-(2-substituted-pyrrol-1-yl)alkyl)pyran-2-one inhibitors of cholesterol synthesis |
US5097045A (en) | 1989-02-01 | 1992-03-17 | Warner-Lambert Company | Process for trans-6-[2-(substituted-pyrrol-1-yl)alkyl]pyran-2-one inhibitors of cholesterol synthesis |
US5245047A (en) | 1988-02-22 | 1993-09-14 | Warner-Lambert Company | Process for trans-6-[2-(substituted-pyrrol-1-yl)alkyl]pyran-2-one inhibitors of cholesterol synthesis |
US5216174A (en) | 1988-02-22 | 1993-06-01 | Warner-Lambert Co. | Process for trans-6-[12-(substituted-pyrrol-1-yl)alkyl]pyran-2-one inhibitors of cholesterol synthesis |
US5003080A (en) | 1988-02-22 | 1991-03-26 | Warner-Lambert Company | Process for trans-6-(2-(substituted-pyrrol-1-yl)alkyl)pryan-2-one inhibitors of cholesterol synthesis |
US5149837A (en) | 1988-02-22 | 1992-09-22 | Warner-Lambert Company | Process for trans-6-[2-(substituted-pyrrol-1-yl)alkyl]pyran-2-one inhibitors of cholesterol synthesis |
US5248793A (en) | 1990-10-17 | 1993-09-28 | Warner-Lambert Company | Process for the synthesis of (4R-cis)-1,1-dimethylethyl 6-iodomethyl or 6-(phenyl-substituted)sulfonyloxymethyl-2,2-dimethyl-1,3-dioxane-4-acetate |
US5103024A (en) | 1990-10-17 | 1992-04-07 | Warner-Lambert Company | Process for the synthesis of (4r-cis)-1,1-dimethylethyl 6-cyanomethyl-2,2-dimethyl-1,3-dioxane-4-acetate |
US5155251A (en) | 1991-10-11 | 1992-10-13 | Warner-Lambert Company | Process for the synthesis of (5R)-1,1-dimethylethyl-6-cyano-5-hydroxy-3-oxo-hexanoate |
US5298627A (en) | 1993-03-03 | 1994-03-29 | Warner-Lambert Company | Process for trans-6-[2-(substituted-pyrrol-1-yl)alkyl]pyran-2-one inhibitors of cholesterol synthesis |
HRP960313B1 (en) * | 1995-07-17 | 2002-08-31 | Warner Lambert Co | Form iii crystalline (r- (r*, r*)-2- (4-fluorophenyl) -beta-delta-hydroxy-5-(1-methylethyl) -3-phenyl-4- ((phenylamino) carbonyl -1h-pyrrole-1-heptanoic acid calcium salt (2:1) |
CZ294740B6 (cs) * | 1995-07-17 | 2005-03-16 | Warner-Lambert Company | Krystalická forma IV atorvastatinu nebo jeho hydrátu, farmaceutický přípravek obsahující tuto krystalickou formu IV atorvastatinu a její použití v lékařství |
US6087511A (en) | 1996-07-16 | 2000-07-11 | Warner-Lambert Company | Process for the production of amorphous [R-(R*,R*)]-2-(4-fluorophenyl)-β,δ-dihydroxy-5-(1-methylethyl )-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrole-1-heptanoic acid) calcium salt (2:1) |
US5929156A (en) | 1997-05-02 | 1999-07-27 | J.M. Huber Corporation | Silica product for use in elastomers |
HU226640B1 (en) | 1999-10-18 | 2009-05-28 | Egis Gyogyszergyar Nyilvanosan | Process for producing amorphous atorvastatin calcium salt |
DE60044884D1 (de) * | 1999-11-17 | 2010-10-07 | Teva Pharma | Verfahren zur Herstellung einer polymorphen Form von Atorvastatin calcium |
WO2002041834A2 (en) * | 2000-11-03 | 2002-05-30 | Teva Pharmaceutical Industries, Ltd. | Atorvastatin hemi-calcium form vii |
IL155890A0 (en) * | 2000-11-16 | 2003-12-23 | Teva Pharma | HYDROLYSIS OF [R(R*,R*)]-2-(4-FLUOROPHENYL)-beta,delta-DIHYDROXY-5-(1-METHYLETHYL)-3-PHENYL-4-[(PHENYLAMINO)CARBONYL]-1H-PYRROLE-1-HEPTANOIC ACID ESTERS WITH CALCIUM HYDROXIDE |
IL156055A0 (en) * | 2000-11-30 | 2003-12-23 | Teva Pharma | Novel crystal forms of atorvastatin hemi calcium and processes for their preparation as well as novel processes for preparing other forms |
CA2623600A1 (en) * | 2000-12-27 | 2002-07-04 | Paul Adrian Van Der Schaaf | Crystalline forms of atorvastatin |
WO2002057229A1 (en) * | 2001-01-19 | 2002-07-25 | Biocon India Limited | FORM V CRYSTALLINE [R-(R*,R*)]-2-(4-FLUOROPHENYL)-ß,$G(D)-DIHYDROXY-5-(1-METHYLETHYL)-3-PHENYL-4-[(PHENYLAMINO)CARBONYL]-1H-PYRROLE-1- HEPTANOIC ACID HEMI CALCIUM SALT. (ATORVASTATIN) |
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2002
- 2002-01-07 CN CNB028150708A patent/CN100471836C/zh not_active Expired - Fee Related
- 2002-01-07 MX MXPA04000889A patent/MXPA04000889A/es active IP Right Grant
- 2002-01-07 KR KR10-2004-7000093A patent/KR20040019043A/ko not_active Application Discontinuation
- 2002-01-07 PL PL02368647A patent/PL368647A1/xx unknown
- 2002-01-07 CZ CZ2004126A patent/CZ2004126A3/cs unknown
- 2002-01-07 EP EP02724877A patent/EP1414796A1/de not_active Withdrawn
- 2002-01-07 RU RU2004103470/04A patent/RU2304139C2/ru not_active IP Right Cessation
- 2002-01-07 IL IL15962602A patent/IL159626A0/xx unknown
- 2002-01-07 BR BR0211488-7A patent/BR0211488A/pt not_active Application Discontinuation
- 2002-01-07 JP JP2003517018A patent/JP2005500351A/ja active Pending
- 2002-01-07 NZ NZ530785A patent/NZ530785A/en not_active IP Right Cessation
- 2002-01-07 EP EP10010845A patent/EP2292600A1/de not_active Withdrawn
- 2002-01-07 AU AU2002255479A patent/AU2002255479B2/en not_active Ceased
- 2002-01-07 CA CA002454500A patent/CA2454500C/en not_active Expired - Fee Related
- 2002-01-07 EE EEP200400048A patent/EE200400048A/xx unknown
- 2002-01-07 WO PCT/US2002/000431 patent/WO2003011826A1/en active IP Right Grant
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2003
- 2003-12-29 IL IL159626A patent/IL159626A/en not_active IP Right Cessation
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2004
- 2004-01-09 BG BG108518A patent/BG108518A/xx unknown
- 2004-01-26 HR HR20040077A patent/HRP20040077A2/xx not_active Application Discontinuation
- 2004-01-26 ZA ZA200400573A patent/ZA200400573B/en unknown
- 2004-01-29 NO NO20040390A patent/NO20040390L/no not_active Application Discontinuation
Non-Patent Citations (2)
Title |
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None * |
See also references of WO03011826A1 * |
Also Published As
Publication number | Publication date |
---|---|
CN1537098A (zh) | 2004-10-13 |
BR0211488A (pt) | 2004-08-17 |
PL368647A1 (en) | 2005-04-04 |
CZ2004126A3 (cs) | 2004-12-15 |
JP2005500351A (ja) | 2005-01-06 |
ZA200400573B (en) | 2005-05-11 |
RU2304139C2 (ru) | 2007-08-10 |
KR20040019043A (ko) | 2004-03-04 |
IL159626A0 (en) | 2004-06-01 |
EE200400048A (et) | 2004-04-15 |
HRP20040077A2 (en) | 2004-06-30 |
CA2454500A1 (en) | 2003-02-13 |
WO2003011826A1 (en) | 2003-02-13 |
EP2292600A1 (de) | 2011-03-09 |
NO20040390L (no) | 2004-01-29 |
RU2004103470A (ru) | 2005-06-20 |
IL159626A (en) | 2013-04-30 |
AU2002255479B2 (en) | 2008-09-11 |
MXPA04000889A (es) | 2004-06-03 |
NZ530785A (en) | 2005-10-28 |
BG108518A (en) | 2004-08-31 |
CN100471836C (zh) | 2009-03-25 |
CA2454500C (en) | 2009-11-10 |
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