ES2478302T3 - Polimorfo A de Ibandronato - Google Patents
Polimorfo A de Ibandronato Download PDFInfo
- Publication number
- ES2478302T3 ES2478302T3 ES06706375.0T ES06706375T ES2478302T3 ES 2478302 T3 ES2478302 T3 ES 2478302T3 ES 06706375 T ES06706375 T ES 06706375T ES 2478302 T3 ES2478302 T3 ES 2478302T3
- Authority
- ES
- Spain
- Prior art keywords
- pentyl
- methyl
- hydroxypropan
- amino
- water
- 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.)
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Links
- MPBVHIBUJCELCL-UHFFFAOYSA-N Ibandronate Chemical compound CCCCCN(C)CCC(O)(P(O)(O)=O)P(O)(O)=O MPBVHIBUJCELCL-UHFFFAOYSA-N 0.000 title abstract description 9
- 229940015872 ibandronate Drugs 0.000 title abstract description 9
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical class [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 abstract description 4
- 238000000034 method Methods 0.000 abstract description 3
- 239000000203 mixture Substances 0.000 abstract description 3
- 238000002360 preparation method Methods 0.000 abstract description 3
- 239000000843 powder Substances 0.000 abstract description 2
- 238000002441 X-ray diffraction Methods 0.000 abstract 1
- 239000002253 acid Substances 0.000 abstract 1
- 150000004682 monohydrates Chemical class 0.000 abstract 1
- 229910000096 monohydride Inorganic materials 0.000 abstract 1
- 238000005496 tempering Methods 0.000 abstract 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 239000000243 solution Substances 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- OIFBSDVPJOWBCH-UHFFFAOYSA-N Diethyl carbonate Chemical compound CCOC(=O)OCC OIFBSDVPJOWBCH-UHFFFAOYSA-N 0.000 description 2
- 238000005079 FT-Raman Methods 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 239000007853 buffer solution Substances 0.000 description 2
- 238000002329 infrared spectrum Methods 0.000 description 2
- 230000005855 radiation Effects 0.000 description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 description 1
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 1
- 229910001218 Gallium arsenide Inorganic materials 0.000 description 1
- 238000003841 Raman measurement Methods 0.000 description 1
- 238000001237 Raman spectrum Methods 0.000 description 1
- 238000010533 azeotropic distillation Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000003926 complexometric titration Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 235000010299 hexamethylene tetramine Nutrition 0.000 description 1
- VKYKSIONXSXAKP-UHFFFAOYSA-N hexamethylenetetramine Chemical compound C1N(C2)CN3CN1CN2C3 VKYKSIONXSXAKP-UHFFFAOYSA-N 0.000 description 1
- 238000000691 measurement method Methods 0.000 description 1
- 229960004011 methenamine Drugs 0.000 description 1
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 1
- 238000000634 powder X-ray diffraction Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 239000013557 residual solvent Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- ISIJQEHRDSCQIU-UHFFFAOYSA-N tert-butyl 2,7-diazaspiro[4.5]decane-7-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCCC11CNCC1 ISIJQEHRDSCQIU-UHFFFAOYSA-N 0.000 description 1
- 238000002834 transmittance Methods 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 125000002256 xylenyl group Chemical class C1(C(C=CC=C1)C)(C)* 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/3804—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)] not used, see subgroups
- C07F9/3839—Polyphosphonic acids
- C07F9/3873—Polyphosphonic acids containing nitrogen substituent, e.g. N.....H or N-hydrocarbon group which can be substituted by halogen or nitro(so), N.....O, N.....S, N.....C(=X)- (X =O, S), N.....N, N...C(=X)...N (X =O, S)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- 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
- A61P3/12—Drugs for disorders of the metabolism for electrolyte homeostasis
- A61P3/14—Drugs for disorders of the metabolism for electrolyte homeostasis for calcium homeostasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Physical Education & Sports Medicine (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Rheumatology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Endocrinology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Un procedimiento para la preparación de polimorfo cristalino del monohidrAto de la sal monosódic del ácido 3-(Nmetil- N-pentil) amino-1-hidroxipropan-1-difosfónico, (Ibandronato) que se caracteriza por un patrón de difracción de rayos x de polvos que tiene picos característicos expresados en el ángulo 2-theta a aproximadamente Ángulo 2-theta**Fórmula** que comprende templar una sal monosódica del ácido 3-(N-metil-N-pentil)amino-1-hidroxipropan-1,1-difosfónico o un monohidrato, una forma polimorfa o una mezcla polimorfa respectiva a una temperatura de 30ºC a 90ºC.
Description
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E06706375
07-07-2014
dores y se expusieron a radiación CuKα. La radiación difractada a los niveles entramados se convierte en señales electrónicas mediante un contador de destellos y se procesa mediante el soporte informático “Diffrac plus”. Los patrones de difracción de rayos X de polvos de los polimorfos A y B individuales de Ibandronato cristalino se muestran en la Figura 1 y 4.
Método de medición de IR Los espectros IR de los polimorfos A y B individuales de Ibandronato cristalino se registraron como una película de la suspensión Nujol que consiste en aprox. 15mg de muestra en aprox. 15mg de Nujol entre dos placas de cloruro de sodio. Las mediciones se llevaron a cabo con un espectrofotómetro FT-IR (IFS55 (Bruker) o el instrumento equivalente) en el modo de transmitancia (resolución 4 cm-1, detector: DTGS). Los espectros IR de los polimorfos A y B individuales de Ibandronato cristalino se muestran en las Figuras 2 y 5.
Método de medición Raman Los espectros Raman de los polimorfos A y B individuales de Ibandronato cristalino se registraron como muestras de alrededor de 20mg del polvo y se rellenaron en un tubo de cristal (tubo acortado de RMN). Las muestras se miden con el FT-Raman de Nicolet acoplado a un Magna 860 (Nicolet) a 90° de la situación de la dispersión, detector: In-GaAs. Resolución de los parámetros de medición 8cm-1; potencia láser 0,95W, Nº de exploración 300. Los espectros FT-Raman de los polimorfos A y B individuales de Ibandronato cristalino se mostraron en las Figuras 3 y 6.
Medición de la solubilidad La solubilidad de los polimorfos A y B individuales de Ibandronato cristalino se midió para varias soluciones. Aproximadamente 10g de los correspondientes polimorfos A y B se suspendieron en tres soluciones tampón diferentes a pH2, pH4 (tampón Titrisol, citrato/HCl), a pH7 (tampón metenamina, HCl) o en agua. La suspensión se agitó durante 24 horas a 25°C y se mantuvo 24 horas adicionales sin agitar a la misma temperatura. La solubilidad se calculó mediante tritación de acuerdo con el método siguiente.
El residuo se filtró, se cogió 2ml del filtrado, se añadieron 5ml de solución Titriplex III y se diluyó con agua hasta 100 ml. Se añadió 2ml de esta solución a aproximadamente 0,1ml de indicador naranja de xilenol y el pH se ajustó hasta 6,5 añadiendo porciones pequeñas de solución tampón de metamina o ácido clorhídrico 0,1M. La solución se tritó inmediatamente con complejo naranja de Th-DCTA-xilenol hasta que el color cambia de amarillo a violeta rojizo. El criterio de evaluación se determina fotométricamente.
Los resultados se encuentran en la siguiente tabla
- Solubilidad del Polimorfo A en [g/l]
- Solubilidad del Polimorfo B en [g/l]*
- pH 2
- 280 274
- pH 4
- 276 278
- pH 7
- 292 299
- agua
- 278 279
*al menos bajo la conversión parcial a polimorfo A
Ejemplo de referencia 1
Preparación de la sal monosódica del ácido 3-(N-metil-N-pentil) amino-1-hidroxipropan-1,1-difosfónico 250g (1,19mol) de clorhidrato de N-metil-N-pentil-�-alanina, 233g (2,84mol) de ácido fosforoso, 151ml (1,65mol) oxicloruro fosforoso y 900ml de carbonato de dietilo se calentaron por pasos hasta 80°C. Después de 2 horas de tiempo de reacción bajo calentamiento continuo, la mezcla se enfrió hasta 60°C y se añadieron 1733ml de agua desmineralizada, seguido de destilación azeotrópica de carbonato de dietilo/agua a 90 hasta 101°C. Se añadieron 358ml de agua desmineralizada, la mezcla se llevó a reflujo y se eliminó el agua por destilación. Se añadieron 316ml de agua desmineralizada y se eliminó el agua destilando dos veces. Finalmente se añadieron 2040ml de agua desmineralizada y el residuo se enfrió hasta 24°C. El pH se ajustó a 23°C con solución de hidróxido de sodio (50%) hasta 4,4. en consecuencia, se añadieron 1100ml de etanol para empezar la cristalización. La suspensión se agitó durante 8 horas a 21 hasta 22°C. Se separó el sólido, se lavó con 344ml de etanol frío/agua desmineralizada (7/5 V/V), a continuación con 344ml de acetona/agua desmineralizada (5/2 V/V) y se secó a 60°C. Se obtuvieron 315,6g (73,7 %) del producto del título en forma de cristales incoloros.
Ensayo (titración complejométrica): 100,6% (calculado sobre bases anhidras y libres de solvente)
Solventes residuales: 2,3% etanol (GC) 3,9% agua (KF)
Ejemplo de referencia 2
Preparación del polimorfo B de Ibandronato cristalino 55g de la sal monosódica del ácido 3-(N-metil-N-pentil) amino-1-hidroxipropan-1,1-difosfónico (obtenida de acuerdo
6
Claims (1)
-
imagen1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP05100686 | 2005-02-01 | ||
| EP05100686 | 2005-02-01 | ||
| PCT/EP2006/000580 WO2006081963A1 (en) | 2005-02-01 | 2006-01-24 | Ibandronate polymorph a |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2478302T3 true ES2478302T3 (es) | 2014-07-21 |
Family
ID=36090730
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES06706375.0T Active ES2478302T3 (es) | 2005-02-01 | 2006-01-24 | Polimorfo A de Ibandronato |
| ES13161008T Active ES2712644T3 (es) | 2005-02-01 | 2006-01-24 | Uso médico del polimorfo A de Ibandronato |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES13161008T Active ES2712644T3 (es) | 2005-02-01 | 2006-01-24 | Uso médico del polimorfo A de Ibandronato |
Country Status (25)
| Country | Link |
|---|---|
| US (1) | US7714158B2 (es) |
| EP (2) | EP2662380B1 (es) |
| JP (2) | JP5828608B2 (es) |
| KR (1) | KR100908529B1 (es) |
| CN (1) | CN101111504B (es) |
| AR (1) | AR053012A1 (es) |
| AU (1) | AU2006210009B2 (es) |
| BR (1) | BRPI0607092A2 (es) |
| CA (1) | CA2594802C (es) |
| CY (1) | CY1121703T1 (es) |
| DK (1) | DK2662380T3 (es) |
| ES (2) | ES2478302T3 (es) |
| HU (1) | HUE042316T2 (es) |
| IL (1) | IL184562A (es) |
| LT (1) | LT2662380T (es) |
| MX (1) | MX2007009107A (es) |
| NO (1) | NO20073723L (es) |
| PL (1) | PL2662380T3 (es) |
| PT (1) | PT2662380T (es) |
| RU (1) | RU2368617C2 (es) |
| SI (1) | SI2662380T1 (es) |
| TR (1) | TR201902609T4 (es) |
| TW (1) | TWI374889B (es) |
| WO (1) | WO2006081963A1 (es) |
| ZA (1) | ZA200706168B (es) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE602005025977D1 (de) | 2004-08-23 | 2011-03-03 | Teva Pharma | Kristalline form des ibandronat-natriums und herstellungsverfahren dafür |
| EP2363401A1 (en) * | 2005-02-01 | 2011-09-07 | F. Hoffmann-La Roche AG | Ibandronate polymorph B |
| WO2007074475A2 (en) * | 2005-12-27 | 2007-07-05 | Natco Pharma Limited | Novel polymorphic forms of ibandronate |
| EP2041148A1 (en) * | 2006-07-03 | 2009-04-01 | Generics Ýuk¨Limited | Novel process for the preparation of bisphosphonic acids |
| US20090012047A1 (en) * | 2006-11-16 | 2009-01-08 | Eran Turgeman | Crystalline forms of ibandronate sodium |
| CA2570949A1 (en) * | 2006-12-12 | 2008-06-12 | Apotex Pharmachem Inc. | Ibandronate sodium propylene glycol solvate and processes for the preparation thereof |
| EP2144919B1 (en) * | 2007-04-11 | 2015-12-02 | F. Hoffmann-La Roche AG | Multi step synthesis of ibandronate |
| EP2316840A1 (en) | 2007-04-19 | 2011-05-04 | Dr. Reddy's Laboratories Limited | Ibandronate Sodium Polymorphs |
| US20090042839A1 (en) * | 2007-08-09 | 2009-02-12 | Sharon Avhar-Maydan | Crystalline forms of ibandronate sodium |
| EP2128166A1 (en) | 2008-05-20 | 2009-12-02 | Chemo Ibérica, S.A. | Polymorphic forms of Ibandronate sodium and processes for preparation thereof |
| EP2180003A1 (en) | 2008-10-21 | 2010-04-28 | Zentiva, k.s. | Preparation of ibandronate trisodium |
| EP2609101B1 (en) | 2010-07-14 | 2015-01-28 | Pharmathen S.A. | Process for the preparation of 3-(n-methyl-n-pentyl)amino-1-hydroxypropane-1,1-diphosphonic acid salt or derivatives thereof |
| TR201200588A2 (tr) | 2012-01-18 | 2012-07-23 | Koçak Farma İlaç Ve Ki̇mya Sanayi̇ Anoni̇m Şi̇rketi̇ | Sodyum ibandronat monohidrat polimorflarini ve polimorflu karışımlarını hazırlamak için prosesler. |
| KR20200085441A (ko) | 2019-01-07 | 2020-07-15 | 엠에프씨 주식회사 | 이반드로네이트의 신규한 결정형 및 이의 제조방법 |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3623397A1 (de) * | 1986-07-11 | 1988-01-14 | Boehringer Mannheim Gmbh | Neue diphosphonsaeurederivate, verfahren zu deren herstellung und diese verbindungen enthaltende arzneimittel |
| TW198039B (es) * | 1988-11-28 | 1993-01-11 | Ciba Geigy Ag | |
| IT1303672B1 (it) * | 1998-07-28 | 2001-02-23 | Nicox Sa | Sali nitrati di farmaci attivi nei disordini ossei |
| EP0998932A1 (de) | 1998-10-09 | 2000-05-10 | Boehringer Mannheim Gmbh | Feste pharmazeutische Darreichungsform enthaltend Diphosphonsäure oder deren Salze und Verfahren zu ihrer Herstellung |
| HUP0104206A3 (en) | 1998-10-16 | 2002-06-28 | Akzo Nobel Nv | High purity composition comprising (7alpha,17alpha)- 17-hydroxy- 7-methyl- 19nor-17-pregn-5(10)-en-20-yn-3-one and process for its preparation |
| TR200101546T2 (tr) | 1998-12-04 | 2001-11-21 | Roche Diagnostics Gmbh | İç-protezlerde kemik entegrasyonunu iyileştirmek üzere ibandronat kullanılması. |
| US6677320B2 (en) | 2000-01-20 | 2004-01-13 | Hoffmann-La Roches Inc. | Parenteral bisphosphonate composition with improved local tolerance |
| CN1404836A (zh) * | 2001-09-14 | 2003-03-26 | 中生北方生物工程开发研究所 | 埃本膦酸钠作为预防和治疗骨质疏松症的药物的有效成分的应用 |
| WO2003095029A1 (en) | 2002-05-10 | 2003-11-20 | F. Hoffmann-La Roche Ag | Bisphosphonic acid for the treatment and prevention of osteoporosis |
| RU2315603C2 (ru) | 2002-12-20 | 2008-01-27 | Ф.Хоффманн-Ля Рош Аг | Композиция с высокой дозой ибандроната |
| MX2007000087A (es) * | 2004-06-23 | 2007-11-06 | Teva Pharma | Acido ibandronico solido y cristalino. |
| DE602005025977D1 (de) * | 2004-08-23 | 2011-03-03 | Teva Pharma | Kristalline form des ibandronat-natriums und herstellungsverfahren dafür |
-
2006
- 2006-01-24 HU HUE13161008A patent/HUE042316T2/hu unknown
- 2006-01-24 PT PT13161008T patent/PT2662380T/pt unknown
- 2006-01-24 DK DK13161008.1T patent/DK2662380T3/en active
- 2006-01-24 WO PCT/EP2006/000580 patent/WO2006081963A1/en active Application Filing
- 2006-01-24 EP EP13161008.1A patent/EP2662380B1/en active Active
- 2006-01-24 BR BRPI0607092-2A patent/BRPI0607092A2/pt active Search and Examination
- 2006-01-24 CN CN2006800036914A patent/CN101111504B/zh not_active Expired - Fee Related
- 2006-01-24 EP EP06706375.0A patent/EP1848728B1/en not_active Revoked
- 2006-01-24 KR KR1020077019795A patent/KR100908529B1/ko active IP Right Grant
- 2006-01-24 PL PL13161008T patent/PL2662380T3/pl unknown
- 2006-01-24 SI SI200632318T patent/SI2662380T1/sl unknown
- 2006-01-24 AU AU2006210009A patent/AU2006210009B2/en not_active Ceased
- 2006-01-24 RU RU2007132701/04A patent/RU2368617C2/ru not_active IP Right Cessation
- 2006-01-24 LT LTEP13161008.1T patent/LT2662380T/lt unknown
- 2006-01-24 US US11/338,468 patent/US7714158B2/en active Active
- 2006-01-24 TR TR2019/02609T patent/TR201902609T4/tr unknown
- 2006-01-24 CA CA2594802A patent/CA2594802C/en not_active Expired - Fee Related
- 2006-01-24 MX MX2007009107A patent/MX2007009107A/es active IP Right Grant
- 2006-01-24 ES ES06706375.0T patent/ES2478302T3/es active Active
- 2006-01-24 ES ES13161008T patent/ES2712644T3/es active Active
- 2006-01-24 JP JP2007553502A patent/JP5828608B2/ja active Active
- 2006-01-27 TW TW095103582A patent/TWI374889B/zh not_active IP Right Cessation
- 2006-01-30 AR ARP060100335A patent/AR053012A1/es not_active Application Discontinuation
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2007
- 2007-07-12 IL IL184562A patent/IL184562A/en not_active IP Right Cessation
- 2007-07-18 NO NO20073723A patent/NO20073723L/no not_active Application Discontinuation
- 2007-07-25 ZA ZA200706168A patent/ZA200706168B/xx unknown
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2015
- 2015-06-30 JP JP2015131571A patent/JP6039754B2/ja active Active
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2019
- 2019-02-21 CY CY20191100222T patent/CY1121703T1/el unknown
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