WO2009106825A1 - Polymorphes de sorafénib et leurs sels - Google Patents

Polymorphes de sorafénib et leurs sels Download PDF

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Publication number
WO2009106825A1
WO2009106825A1 PCT/GB2009/000530 GB2009000530W WO2009106825A1 WO 2009106825 A1 WO2009106825 A1 WO 2009106825A1 GB 2009000530 W GB2009000530 W GB 2009000530W WO 2009106825 A1 WO2009106825 A1 WO 2009106825A1
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WO
WIPO (PCT)
Prior art keywords
sorafenib
pharmaceutically acceptable
acceptable salt
amorphous
organic solvent
Prior art date
Application number
PCT/GB2009/000530
Other languages
English (en)
Inventor
Dharmaraj Ramachandra Rao
Rajendra Narayanrao Kankan
Maruti Ghagare
Sandip Chikhalikar
Original Assignee
Cipla Limited
Curtis, Philip Anthony
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 Cipla Limited, Curtis, Philip Anthony filed Critical Cipla Limited
Publication of WO2009106825A1 publication Critical patent/WO2009106825A1/fr

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/81—Amides; Imides

Definitions

  • the present invention relates to an amorphous form of 4-(4- ⁇ 3-[4-chloro-3- (trifluoromethylJpheny ⁇ ureidoJphenoxyJ- ⁇ -methylpyridine ⁇ -carboxamide or its pharmaceutically acceptable salt, processes for the preparation of the amorphous form and compositions comprising it.
  • Sorafenib is commonly known as sorafenib (I). Sorafenib is generally prepared as its tosylate salt.
  • Sorafenib and pharmaceutically acceptable salts thereof are disclosed in WO0042012. Sorafenib is also disclosed in WO0041698. Both these patents also disclose processes for the preparation of sorafenib.
  • WO2006034796 discloses a process for the preparation of sorafenib and its tosylate salt.
  • WO2006034797 also describes various polymorphs of sorafenib tosylate.
  • WO2006034796 acknowledges that sorafenib tosylate prepared by the general method disclosed in WO0042012 gives polymorphic Form Il which is metastable.
  • WO2006034796 itself describes Form I, Form III, an ethanol solvate and a methanol solvate of sorafenib tosylate which are characterized by melting point, Differential Scanning Calorimetry (DSC) and thermogravimetry, X-ray diffraction, IR spectrum, Raman spectrum, NIR spectrum and FIR spectrum.
  • DSC Differential Scanning Calorimetry
  • WO2006034796 also describes various methods for the preparation of Form I, Form III, the methanol solvate and the ethanol solvate.
  • WO2006034796 discloses processes for the preparation of Form I from Form II.
  • the polymorphic form I is claimed in WO2006034797 which involves tedious reaction processes such as long reaction hours, cooling the reaction mixture to very low temperatures such as -25 0 C.
  • the process for preparation of Form I requires critical conditions like cooling at a controlled rate to get Form I.
  • Polymorphism in general means that the drug exists in different physical forms which may be crystalline or non-crystalline. Different polymorphs will have different free energies and therefore different physical properties like solubility, chemical stability, melting point, density, flow characteristics which affects the ease with which the material is handled during processing into pharmaceutical product. Another important property is rate of dissolution i.e. the rate at which drug gets dissolved in patient's stomach.
  • amorphous solids do not possess a distinguishable crystal lattice. In general, amorphous solids are more stable and hence, they are preferred in formulating pharmaceutical compositions. Further, amorphous solids usually have better bioavailability.
  • WO2008008733 discloses compositions comprising a nanoparticulate sorafenib, or a salt, such as a sorafenib tosylate, or derivative thereof. According to the description, the particles can be in crystalline phase, semi-crystalline phase, amorphous phase, semi- amorphous phase, or a combination thereof. However, there is no disclosure of how the various forms are prepared. Objects of the Invention
  • Another aspect of the present invention is to provide a process for the conversion of an amo ⁇ hous form of a pharmaceutically acceptable salt of compound of formula (I) to Form I thereof.
  • a further object of the present invention is to provide a complex of polyvinyl pyrrolidone (PVP) with a compound of formula (I) or a pharmaceutically acceptable salt thereof.
  • PVP polyvinyl pyrrolidone
  • Another object of the present invention is to provide a process for the preparation of a complex of polyvinyl pyrrolidone (PVP) with a compound of formula (I) or a pharmaceutically acceptable salt thereof.
  • PVP polyvinyl pyrrolidone
  • a pharmaceutical composition comprising a compound of formula (I) or pharmaceutically acceptable salt thereof in an amorphous form or a PVP complex with compound of formula (I) or a pharmaceutically acceptable salt thereof with one or more pharmaceutically acceptable carriers and/or excipients.
  • sorafenib or a pharmaceutically acceptable salt thereof in an amorphous form there is provided sorafenib or a pharmaceutically acceptable salt thereof in an amorphous form.
  • amorphous sorafenib free base there is provided.
  • the amorphous sorafenib free may be characterised by having the XRPD pattern as shown in Figure 1.
  • amorphous sorafenib tosylate in another embodiment, there is provided amorphous sorafenib tosylate.
  • the amorphous sorafenib tosylate may characterised by having the XRPD pattern as shown in Figure 2.
  • a process for the preparation of sorafenib or a pharmaceutically acceptable salt thereof in an amorphous form comprising dissolving sorafenib or a pharmaceutically acceptable salt thereof in an organic solvent and recovering the amorphous material by spray drying or freeze drying.
  • the sorafenib or salt thereof produced by the process may be as described above.
  • the starting material in the process, i.e. the sorafenib or pharmaceutically acceptable salt thereof which is dissolved in the organic solvent may be in any crystalline or other form.
  • the organic solvent may be selected from the group consisting of a ketone, an ether, an amide, an alcohol, a hydrocarbon which may or may not be substituted, a halogenated hydrocarbon and a mixture thereof.
  • the solvent is selected from the group consisting of acetone, methyl isobutyl ketone, tetrahydrofuran, N,N-dimethyl formamide, methanol, ethanol, isopropanol, isobutanol, n-butanol, dimethyl sulfoxide, N-methyl pyrrolidone, toluene, methylene dichloride and a mixture thereof.
  • a process for preparing sorafenib tosylate Form I comprising: a) suspending amorphous sorafenib tosylate in an organic solvent whereby a crystalline solid precipitates; and b) isolating the crystalline solid.
  • Isolation may be by any conventional technique well known to the skilled person.
  • the isolation may be by filtration or solvent distillation, then drying in a vacuum.
  • the organic solvent may be selected from the group consisting of an alcohol, an ester, an ether, a ketone, an amide, a hydrocarbon which may or may not be substituted, a halogenated hydrocarbon, and a mixture thereof.
  • the solvent is selected from the group consisting of methanol, ethanol, isopropanol, n-butanol, isobutanol, ethyl acetate, diisopropyl ether, acetone, methyl isobutyl ketone, ethyl methyl ketone, N, N- dimethyl formamide, dimethyl sulfoxide, toluene, hexane, methylene dichloride, ethylene dichloride and a mixture thereof.
  • the temperature during step a) ranges from around 25 0 C to around 4O 0 C. More preferably from around 25°C to around 35°C.
  • the reaction mass in step a) is stirred for a period of time ranging from around 5 hours to around 24 hours, preferably for a period of time ranging from around 12 hours to around 14 hours.
  • PVP polyvinyl pyrrolidone
  • the sorafenib or salt thereof is in amorphous form, which form is as described above.
  • the sorafenib or salt thereof is not in amorphous form, i.e. the sorafenib or salt thereof is in crystalline form.
  • the complex may comprise crystalline Form I sorafenib tosylate and PVP.
  • the complex comprises sorafenib free base and PVP, suitably amorphous sorafenib free base and PVP.
  • the complex comprises a salt of sorafenib, suitably in amorphous form, and PVP.
  • the complex comprises sorafenib tosylate, suitably amorphous sorafenib tosylate, and PVP.
  • the PVP is present in an amount of around 5% to around 50% by weight of sorafenib or its pharmaceutically acceptable salt, preferably in an amount of around 10% to around 40% by weight of sorafenib or its pharmaceutically acceptable salt, more preferably around 20% to around 30% by weight of sorafenib or its pharmaceutically acceptable salt, most preferably in an amount of around 25% by weight of sorafenib or its pharmaceutically acceptable salt.
  • Isolation may be by any conventional technique well known to the skilled person. For example, the isolation may be by filtration or concentration and then drying.
  • the solution or suspension in step a) is heated.
  • the first organic solvent is selected from the group consisting of a ketone, an ether, an alcohol, an amide, or a hydrocarbon which may or may not be substituted and a mixture thereof.
  • the first organic solvent is selected from the group consisting of acetone, tetrahydrofuran, dioxane, a Ci-C 4 alcohol, N,N-dimethyl formamide, dimethyl sulfoxide and mixtures thereof.
  • the C1-C4 alcohol may be, for example, methanol, ethanol, isopropanol, isobutanol or n-butanol.
  • the second organic solvent is selected from the group consisting of an alcohol, an ether and a mixture thereof.
  • the second organic solvent is selected from the group consisting of a CrC 4 alcohol, tetrahydrofuran and a mixture thereof.
  • the Ci-C 4 alcohol may be, for example, methanol, ethanol, isopropanol, isobutanol or n- butanol.
  • compositions contain an effective amount of the amorphous form of sorafenib or its pharmaceutically acceptable salt.
  • the "effective amount” means an amount of a compound of the present invention which is effective for prevention or treatment of the various cancers.
  • the pharmaceutical composition may be in a form suitable for administration orally, parenterally, transdermal ⁇ or nasally.
  • the composition is in the form of a tablet, a hard or soft gelatin capsule, a sub-lingual tablet, a dry syrup, a suspension, a sachet, an aqueous or non-aqueous solution or emulsion, a spray, a patch or an aerosol delivery system.
  • the sorafenib or salt thereof may be in micronized form.
  • a method of treating cancer in a subject comprising administering to the subject an effective amount of sorafenib or a pharmaceutically acceptable salt thereof as described above, or a complex as described above or a pharmaceutical composition as described above.
  • the invention provides compound of formula (I), i.e. sorafenib, or a pharmaceutically acceptable salt thereof in an amorphous form.
  • the invention provides a process for the preparation of sorafenib or a pharmaceutically acceptable salt thereof in an amorphous form.
  • the process involves dissolving sorafenib or a pharmaceutically acceptable salt thereof in a suitable solvent and recovering the amorphous material by suitable means.
  • the suitable means which may be used to recover the amorphous form of sorafenib or its pharmaceutically acceptable salt include spray drying, freeze drying, preferably spray drying.
  • the sorafenib or pharmaceutically acceptable salt thereof which is dissolved to form a clear solution may be in any crystalline or other form, including the form of a solvate or hydrate.
  • the solvent may be selected according to the technique and conditions used.
  • the solvent may be any organic solvent or mixture thereof and may be selected from a ketone, an ether, an amide, an alcohol, a hydrocarbon which may or may not be substituted, and a halogenated hydrocarbon.
  • the solvent may be selected from but not limited to acetone, methyl isobutyl ketone, tetrahydrofuran, N,N-dimethyl formamide, methanol, ethanol, isopropanol, isobutanol, n- butanol, dimethyl sulfoxide, N-methyl pyrrolidone, toluene, methylene dichloride.
  • the amorphous form of sorafenib or a pharmaceutically acceptable salt thereof may be micronized and used in a suitable pharmaceutical formulation.
  • amorphous sorafenib tosylate may be converted to sorafenib tosylate Form I.
  • the process for conversion of amorphous sorafenib tosylate to Form I of sorafenib tosylate comprises the following steps:
  • amorphous sorafenib tosylate is suspended in a suitable solvent and at a suitable temperature and the suspension is then stirred to obtain a crystalline solid; b) the crystalline solid is isolated for example by filtration or by solvent distillation and drying in a vacuum.
  • the solvent used in the conversion process may be any organic solvent or mixture thereof which may be selected from an alcohol, an ester, an ether, a ketone, an amide, a hydrocarbon which may or may not be substituted, and a halogenated hydrocarbon.
  • the solvents may be selected from but not limited to methanol, ethanol, isopropanol, n- butanol, isobutanol, ethyl acetate, diisopropyl ether, acetone, methyl isobutyl ketone, ethyl methyl ketone, N,N-dimethyl formamide, dimethyl sulfoxide, toluene, hexane, methylene dichloride, ethylene dichloride.
  • the temperature at which amorphous sorafenib tosylate is suspended may be range from around 25°C to around 40 0 C, more preferably from around 25°C to around 35°C.
  • the suspension may be stirred for a period of time ranging from around 5 hours to around 24 hours, preferably for a period of time ranging from around 12 hours to around 14 hours.
  • a complex of sorafenib or its pharmaceutically acceptable salt with polyvinyl pyrrolidone provides a process for preparing a complex of sorafenib or a pharmaceutically acceptable salt thereof with polyvinyl pyrrolidone (PVP) which process comprises the following steps: a) sorafenib or a pharmaceutically acceptable salt thereof is dissolved or suspended in a first suitable solvent; b) PVP is dissolved in a second suitable solvent; c) the solution of PVP is added to the solution or suspension prepared in step a) and the mixture is stirred and isolated, for example by either filtration or concentration and then drying.
  • the solution or suspension in step a) may be heated.
  • the first solvent used to dissolve sorafenib or its pharmaceutically acceptable salt may be any organic solvent for example selected from a ketone, an ether, an alcohol, an amide, or a hydrocarbon which may or may not be substituted.
  • the solvent may be used either alone or as a mixture with another solvent.
  • the first solvent may be selected from but not limited to acetone, tetrahydrofuran, dioxane, C r C 4 alcohols like methanol, ethanol, isopropanol, isobutanol, n-butanol, N,N-dimethyl formamide, dimethyl sulfoxide.
  • the second solvent used to dissolve PVP may be selected from any organic solvent selected for example selected from an alcohols or an ether.
  • the solvent may be used either alone or as a mixture with another solvent.
  • the second solvent may be selected from but not limited to a Ci-C 4 alcohol such as methanol, ethanol, isopropanol, isobutanol or n-butanol, or tetrahydrofuran.
  • the percentage of PVP may be range from around 5% to around 50% by weight of sorafenib or its pharmaceutically acceptable salt. The preferred percentage is 25%.
  • the present invention provides pharmaceutical compositions which contain an effective amount of the amorphous form of sorafenib or its pharmaceutically acceptable salt together with one or more pharmaceutically acceptable carriers.
  • the "effective amount” means an amount of a compound of the present invention which is effective for prevention or treatment of the various cancers.
  • compositions may be prepared as medicaments to be administered orally, parenterally, transdermal ⁇ or nasally.
  • Suitable forms of oral administration include tablets, hard or soft gelatin capsules, sublingual tablets, dry syrups, suspensions, sachets.
  • Suitable forms of parenteral administration include an aqueous or non-aqueous solution or emulsion while transdermal administration includes spray, patches and other known forms.
  • Nasal administration includes suitable aerosol delivery systems known in the art.
  • excipients and the amounts to use may be readily determined by the formulation scientist based upon experience and standard procedures available or known.
  • Figure Il is an X-ray powder diffractogram (XRD) of tosylate salt of compound of formula (I) in an amorphous form.
  • Figure III is an X-ray powder diffractogram (XRD) of Form I of tosylate salt of compound of formula (I).
  • Sorafenib base (50 g) was dissolved in acetone (2.5 lit, 50 vol) at 25 -30 0 C under stirring for 1 hour. It was then fed to spray dryer unit via peristaltic pump and spray dried at 45 - 50 0 C. The spray dried material thus obtained was collected from the spray dryer chamber 5 and dried in vacuum oven at 45 - 50 0 C for 12 - 14 hours under vacuum to obtain amorphous sorafenib (45 g).
  • Sorafenib tosylate 50 g was dissolved in N,N-Dimethyl formamide (100 ml, 2 vol.) at 25 - 10 30 0 C under stirring for 10 minutes. It was then fed carefully to spray dryer unit via peristaltic pump and spray dried at 195 - 200 0 C. The spray dried material thus obtained was collected from the spray dryer chamber and dried in vacuum oven at 80 - 90 0 C for 3 - 4 days under high capacity vacuum to get sorafenib tosylate (35 g) which is amorphous in nature. 15
  • Sorafenib tosylate 100 g was dissolved in N-methyl pyrrolidone (300 ml, 3 vol.) at 25 - 30 0 C under stirring for 30 minutes. It was then fed carefully to spray dryer unit via peristaltic pump and spray dried at 220 - 230°C. The spray dried material thus obtained 20 was collected from the spray dryer chamber and dried in vacuum oven at 70 - 80°C for 5 - 6 days under high capacity vacuum to get sorafenib tosylate (70 g) which is amorphous in nature.
  • Example 4 5 Amorphous sorafenib tosylate (5 g) was suspended in di-isopropyl ether (50 ml) at 25 - 30 0 C. The suspension was then stirred at ambient temperature for 12 - 14 hours where in the yellowish pale solid turned white crystalline in nature. The obtained white solid was then filtered and vacuum dried for 12 - 14 hours at 50 - 60°C. The obtained white crystalline product (4.5 g) is Form I of sorafenib tosylate.
  • Sorafenib base (25 g) was stirred with acetone (1300 ml) at room temperature and atmospheric pressure. The obtained clear solution was then freeze dried under high vacuum using lypholiser. The obtained solid was then dried in vacuum oven at 40 - 50 0 C to remove solvent traces. The material obtained is amorphous sorafenib (20 g).
  • Sorafenib tosylate (13 g) was stirred with N,N-Dimethyl Formamide (30 ml) at room temperature and atmospheric pressure. The obtained clear solution was then freeze dried under high vacuum using lypholiser. The obtained solid was then dried in vacuum oven at 80 - 9O 0 C to remove solvent traces which further yields amorphous form of the sorafenib tosylate (9.8 g).
  • Example 7 Sorafenib tosylate (5 g) was stirred with (1 :1 ) mixture of N,N-Dimethyl formamide and Methanol (50 ml) at room temperature and atmospheric pressure. The obtained clear solution was then freeze dried under high vacuum using lypholiser. The obtained solid was then dried in vacuum oven at 80 - 90 0 C to remove solvent traces to give amorphous sorafenib tosylate (3.8 g).
  • Sorafenib (2 g) was dissolved in tetrahydrofuran (20 ml) in a round bottom flask at 50°C to get clear solution.
  • PVP 0.1 g
  • methanol 2 ml
  • Sorafenib tosylate (2 g) was suspended in ethanol (50 ml) in a round bottom flask at 25- 30 0 C.
  • PVP 0.1 g
  • ethanol 2 ml
  • solution of PVP was added and the mixture was stirred for 16 - 20 hours.
  • the product obtained was filtered and then dried in an oven at 60 0 C for 12 hours to get complex of sorafenib tosylate with PVP (0.7 g).
  • Sorafenib (2 g) was dissolved in tetrahydrofuran (20 ml) in a round bottom flask at 50°C to get clear solution.
  • PVP 0.5 g
  • methanol 4 ml
  • Sorafenib tosylate (2 g) was suspended in ethanol (50 ml) in a round bottom flask at 25- 30 0 C.
  • PVP 0.5 g
  • tetrahydrofuran 4 ml
  • solution of PVP was added and the mixture was stirred for 16 - 20 hours.
  • the product obtained was filtered and then dried in an oven at 60 0 C for 12 hours to get complex of sorafenib tosylate with PVP (1.8 g)-
  • Example 12 Tablets containing amorphous form of sorafenib or its pharmaceutically acceptable salt (active ingredient).
  • Active ingredient microcrystalline cellulose, crosscarmellose sodium, sodium lauryl sulphate & magnesium stearate are sifted separately through suitable sieves and then blended together. The lubricated granules are then compressed into tablets using suitable compression machine.
  • Active ingredient, microcrystalline cellulose, crosscarmellose sodium, sodium lauryl sulphate, hydroxypropyl methylcellulose & magnesium stearate are sifted separately through suitable sieve. Active ingredient, microcrystalline cellulose, crosscarmellose sodium, sodium lauryl sulphate are blended together.
  • the binder is prepared using hydroxypropyl methylcellulose in water. The dry mix is then sprayed with the binder and the blend is then sifted through suitable mesh and lubricated with magnesium stearate. The lubricated granules are then compressed into tablets using suitable compression machine.

Abstract

La présente invention concerne le sorafénib ou l'un de ses sels pharmaceutiquement acceptables sous forme amorphe. La présente invention concerne également un complexe de sorafénib ou d'un de ses sels pharmaceutiquement acceptables avec de la polyvinylpyrrolidone.
PCT/GB2009/000530 2008-02-27 2009-02-25 Polymorphes de sorafénib et leurs sels WO2009106825A1 (fr)

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IN402/MUM/2008 2008-02-27

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Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010142678A2 (fr) * 2009-06-12 2010-12-16 Ratiopharm Gmbh Polymorphes de 4-[4-[[4-chloro-3-(trifluorométhyl)phényl]carbamoylamino]phénoxy]-n-méthyl-pyridine-2-carboxamide
WO2011036648A1 (fr) 2009-09-24 2011-03-31 Ranbaxy Laboratories Limited Polymorphes de sels d'addition acide de sorafénib
WO2011036647A1 (fr) 2009-09-24 2011-03-31 Ranbaxy Laboratories Limited Procédé de préparation de tosylate de sorafénib
WO2011058522A1 (fr) 2009-11-12 2011-05-19 Ranbaxy Laboratories Limited Sel d'ethylsulfonate de sorafenib et son procede de preparation
WO2011092663A2 (fr) 2010-01-29 2011-08-04 Ranbaxy Laboratories Limited Solvate de diméthylsulfoxyde du 4-(4-{3-[4-chloro-3-(trifluorométhyl)phényl]uréido}phénoxy)-n2-méthylpyridine-2-carboxamide
WO2013135187A1 (fr) * 2012-03-15 2013-09-19 苏州泽璟生物制药有限公司 Dispersion solide manifestant une performance d'adsorption améliorée et sa préparation
WO2013175483A1 (fr) * 2012-05-23 2013-11-28 Shilpa Medicare Limited Procédé pour la préparation de tosylate de sorafénib cristallin
CN103896833A (zh) * 2012-12-27 2014-07-02 上海创诺制药有限公司 索拉非尼对甲苯磺酸盐溶剂化物多晶型物及其制法和用途
WO2015031604A1 (fr) 2013-08-28 2015-03-05 Crown Bioscience, Inc. Signatures d'expression génique permettant de prédire la réponse d'un sujet à un inhibiteur multikinase et leurs procédés d'utilisation
RU2568638C1 (ru) * 2015-02-26 2015-11-20 Индивидуальный предприниматель Михайлов Олег Ростиславович КРИСТАЛЛИЧЕСКАЯ β-МОДИФИКАЦИЯ 4-[4-({ [4-ХЛОРО-3-(ТРИФТОРОМЕТИЛ) ФЕНИЛ]КАРБАМОИЛ} АМИНО)ФЕНОКСИ]-N-МЕТИЛ-ПИРИДИН-2-КАРБОКСАМИДА п-ТОЛУОЛСУЛЬФОНАТА, СПОСОБ ЕЁ ПОЛУЧЕНИЯ И ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ НА ЕЁ ОСНОВЕ
CN105439947A (zh) * 2014-12-01 2016-03-30 石药集团中奇制药技术（石家庄）有限公司 一种甲苯磺酸索拉非尼新晶型及其制备方法
RU2766288C2 (ru) * 2020-03-30 2022-03-11 Общество с ограниченной ответственностью "АКСЕЛЬФАРМ" Аморфная форма 4-{ 4-[({ [4-хлор-3-(трифторметил)фенил]амино} карбонил)-амино]фенокси} -n-метилпиридин-2-карбоксамида тозилата (варианты), способ её получения и применение для лечения онкологических заболеваний

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000042012A1 (fr) * 1999-01-13 2000-07-20 Bayer Corporation DIPHENYLUREES A SUBSTITUANTS φ-CARBOXYARYLES, INHIBITRICES DE KINASE RAF
WO2006026501A1 (fr) * 2004-08-27 2006-03-09 Bayer Pharmaceuticals Corporation Nouvelles compositions pharmaceutiques pour le traitement du cancer
WO2006034797A1 (fr) * 2004-09-29 2006-04-06 Bayer Healthcare Ag Forme thermodynamiquement stable de tosylate de bay 43-9006
WO2006094626A1 (fr) * 2005-03-07 2006-09-14 Bayer Healthcare Ag Composition pharmaceutique comprenant une diphénylurée substituée par un oméga-carboxyaryle pour le traitement du cancer
WO2007053573A2 (fr) * 2005-10-31 2007-05-10 Bayer Pharmaceuticals Corporation Traitement du cancer au moyen de sorafenib

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000042012A1 (fr) * 1999-01-13 2000-07-20 Bayer Corporation DIPHENYLUREES A SUBSTITUANTS φ-CARBOXYARYLES, INHIBITRICES DE KINASE RAF
WO2006026501A1 (fr) * 2004-08-27 2006-03-09 Bayer Pharmaceuticals Corporation Nouvelles compositions pharmaceutiques pour le traitement du cancer
WO2006034797A1 (fr) * 2004-09-29 2006-04-06 Bayer Healthcare Ag Forme thermodynamiquement stable de tosylate de bay 43-9006
WO2006094626A1 (fr) * 2005-03-07 2006-09-14 Bayer Healthcare Ag Composition pharmaceutique comprenant une diphénylurée substituée par un oméga-carboxyaryle pour le traitement du cancer
WO2007053573A2 (fr) * 2005-10-31 2007-05-10 Bayer Pharmaceuticals Corporation Traitement du cancer au moyen de sorafenib

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
BANKSTON D. ET AL.: "A Scaleable synthesis of BAY 43-9006: A Potent Raf Kinase Inhibitor for the Treatment of Cancer", ORGANIC PROCESS RESEARCH AND DEVELOPMENT, vol. 6, no. 6, 20 September 2002 (2002-09-20), pages 777 - 781, XP002524977 *
HILFIKER R. ET AL.: "Relevance of Solid-state Properties for Pharmaceutical products", 1 January 2006, POLYMORPHISM IN PHARMACEUTICAL SOLIDS, WILEY-VCH VERLAG, WEINHEIM, PAGE(S) 1-19, XP002525043 *
PETIT S ET AL: "The Amorphous State", 1 January 2006, POLYMORPHISM IN PHARMACEUTICAL SOLIDS, WILEY-VCH VERLAG, WEINHEIM, PAGE(S) 259 - 285, ISBN: 978-3-527-31146-0, XP002481458 *

Cited By (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010142678A3 (fr) * 2009-06-12 2011-03-24 Ratiopharm Gmbh Polymorphes de 4-[4-[[4-chloro-3-(trifluorométhyl)phényl]carbamoylamino]phénoxy]-n-méthyl-pyridine-2-carboxamide
WO2010142678A2 (fr) * 2009-06-12 2010-12-16 Ratiopharm Gmbh Polymorphes de 4-[4-[[4-chloro-3-(trifluorométhyl)phényl]carbamoylamino]phénoxy]-n-méthyl-pyridine-2-carboxamide
WO2011036648A1 (fr) 2009-09-24 2011-03-31 Ranbaxy Laboratories Limited Polymorphes de sels d'addition acide de sorafénib
WO2011036647A1 (fr) 2009-09-24 2011-03-31 Ranbaxy Laboratories Limited Procédé de préparation de tosylate de sorafénib
US8609854B2 (en) 2009-09-24 2013-12-17 Ranbaxy Laboratories Limited Process for the preparation of sorafenib tosylate
US8604208B2 (en) 2009-09-24 2013-12-10 Ranbaxy Laboratories Limited Polymorphs of sorafenib acid addition salts
US8552197B2 (en) 2009-11-12 2013-10-08 Ranbaxy Laboratories Limited Sorafenib ethylsulfonate salt, process for preparation and use
WO2011058522A1 (fr) 2009-11-12 2011-05-19 Ranbaxy Laboratories Limited Sel d'ethylsulfonate de sorafenib et son procede de preparation
WO2011092663A2 (fr) 2010-01-29 2011-08-04 Ranbaxy Laboratories Limited Solvate de diméthylsulfoxyde du 4-(4-{3-[4-chloro-3-(trifluorométhyl)phényl]uréido}phénoxy)-n2-méthylpyridine-2-carboxamide
WO2011092663A3 (fr) * 2010-01-29 2011-12-29 Ranbaxy Laboratories Limited Solvate de diméthylsulfoxyde du 4-(4-{3-[4-chloro-3-(trifluorométhyl)phényl]uréido}phénoxy)-n2-méthylpyridine-2-carboxamide
US8618305B2 (en) 2010-01-29 2013-12-31 Ranbaxy Laboratories Limited Sorafenib dimethyl sulphoxide solvate
WO2013135187A1 (fr) * 2012-03-15 2013-09-19 苏州泽璟生物制药有限公司 Dispersion solide manifestant une performance d'adsorption améliorée et sa préparation
WO2013175483A1 (fr) * 2012-05-23 2013-11-28 Shilpa Medicare Limited Procédé pour la préparation de tosylate de sorafénib cristallin
AU2012380672B2 (en) * 2012-05-23 2015-05-14 Shilpa Medicare Limited Process for preparing crystalline Sorafenib tosylate
CN103896833A (zh) * 2012-12-27 2014-07-02 上海创诺制药有限公司 索拉非尼对甲苯磺酸盐溶剂化物多晶型物及其制法和用途
CN103896833B (zh) * 2012-12-27 2016-12-28 上海创诺制药有限公司 索拉非尼对甲苯磺酸盐溶剂化物多晶型物及其制法和用途
WO2015031604A1 (fr) 2013-08-28 2015-03-05 Crown Bioscience, Inc. Signatures d'expression génique permettant de prédire la réponse d'un sujet à un inhibiteur multikinase et leurs procédés d'utilisation
CN105439947A (zh) * 2014-12-01 2016-03-30 石药集团中奇制药技术（石家庄）有限公司 一种甲苯磺酸索拉非尼新晶型及其制备方法
CN110204483A (zh) * 2014-12-01 2019-09-06 石药集团中奇制药技术（石家庄）有限公司 一种甲苯磺酸索拉非尼新晶型及其制备方法
RU2568638C1 (ru) * 2015-02-26 2015-11-20 Индивидуальный предприниматель Михайлов Олег Ростиславович КРИСТАЛЛИЧЕСКАЯ β-МОДИФИКАЦИЯ 4-[4-({ [4-ХЛОРО-3-(ТРИФТОРОМЕТИЛ) ФЕНИЛ]КАРБАМОИЛ} АМИНО)ФЕНОКСИ]-N-МЕТИЛ-ПИРИДИН-2-КАРБОКСАМИДА п-ТОЛУОЛСУЛЬФОНАТА, СПОСОБ ЕЁ ПОЛУЧЕНИЯ И ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ НА ЕЁ ОСНОВЕ
RU2766288C2 (ru) * 2020-03-30 2022-03-11 Общество с ограниченной ответственностью "АКСЕЛЬФАРМ" Аморфная форма 4-{ 4-[({ [4-хлор-3-(трифторметил)фенил]амино} карбонил)-амино]фенокси} -n-метилпиридин-2-карбоксамида тозилата (варианты), способ её получения и применение для лечения онкологических заболеваний

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