WO2007023182A1 - Delta and epsilon crystal forms of imatinib mesylate - Google Patents
Delta and epsilon crystal forms of imatinib mesylate Download PDFInfo
- Publication number
- WO2007023182A1 WO2007023182A1 PCT/EP2006/065662 EP2006065662W WO2007023182A1 WO 2007023182 A1 WO2007023182 A1 WO 2007023182A1 EP 2006065662 W EP2006065662 W EP 2006065662W WO 2007023182 A1 WO2007023182 A1 WO 2007023182A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- crystalline form
- compound
- formula
- acid addition
- addition salt
- Prior art date
Links
- KTUFNOKKBVMGRW-UHFFFAOYSA-N Cc(c(Nc1nc(-c2cnccc2)ccn1)c1)ccc1NC(c1ccc(CN2CCN(C)CC2)cc1)=O Chemical compound Cc(c(Nc1nc(-c2cnccc2)ccn1)c1)ccc1NC(c1ccc(CN2CCN(C)CC2)cc1)=O KTUFNOKKBVMGRW-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- 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
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
Definitions
- the invention relates to particular crystal forms of the methanesulfonic acid addition salt of 4- (4-methylpiperazin-1-ylmethyl)-N-[4-methyl-3-(4-(pyridin-3-yl)pyrimidin-2-ylamino)phenyl]- benzamide (the compound of formula I, see below), certain processes for their preparation, pharmaceutical compositions containing these crystal forms, and their use in diagnostic methods or, preferably, for the therapeutic treatment of warm-blooded animals, especially humans, and their use as an intermediate or for the preparation of pharmaceutical preparations for use in diagnostic methods or, preferably, for the therapeutic treatment of warm-blooded animals, especially humans.
- lmatinib mesylate also known as lmatinib mesylate or STI571 , the alpha and the beta crystal form thereof, as well as its pharmaceutical use are described in US 6,894,051.
- lmatinib mesylate is the active ingredient of the drug Gleevec® (Glivec®) which is an approved medicament for the treatment of Chronic Myeloid Leukemia (CML) and gastrointestinal stromal tumors (GIST).
- Glivec® is an approved medicament for the treatment of Chronic Myeloid Leukemia (CML) and gastrointestinal stromal tumors (GIST).
- Glivec® is an approved medicament for the treatment of Chronic Myeloid Leukemia (CML) and gastrointestinal stromal tumors (GIST).
- Glivec® is an approved medicament for the treatment of Chronic Myeloid Leukemia (CML) and gastrointestinal stromal tumors (GIST).
- Glivec® is an approved medicament for the treatment of Chronic Myeloid Leukemia (CML)
- the invention relates especially to essentially pure crystal forms, preferably those which are referred to hereinafter as the ⁇ -crystal and the ⁇ -crystal form form, of the methanesulfonic acid addition salt of lmatinib of formula I,
- Fig. 1 shows the X-ray diffraction diagram of the ⁇ -crystal form of the methanesulfonic acid addition salt of a compound of formula I.
- the angle of refraction 2theta is plotted on the horizontal axis (x-axis) and the relative line intensity (background-corrected peak intensity) on the vertical (y-axis).
- the strongest line in the X-ray diffraction diagram is observed at an angle of refraction 2theta of 19.8° having a relative line intensity of 100 %. More broadly, the ⁇ -crystal form is characterized by refractions at angles of refraction 2theta of 19.2° (70), 19.4° (51 ), 19.8° (100), 20.3° (60), 20.7° (52), 20.9° (65) and 21.1 ° (69).
- the ⁇ -crystal form of the methanesulfonic acid addition salt of a compound of formula I is also characterized by lines in the X-ray diffraction diagram observed at an angle of refraction 2theta of 7.8, 8.3 and 9.0.
- Fig. 2 shows the X-ray diffraction diagram of the ⁇ -crystal form of the methanesulfonic acid addition salt of a compound of formula I.
- the angle of refraction 2theta is plotted on the horizontal axis (x-axis) and the relative line intensity (background-corrected peak intensity) on the vertical (y-axis).
- the strongest line in the X-ray diffraction diagram is observed at an angle of refraction 2theta of 20.7° having a relative line intensity of 100 %.
- the ⁇ -crystal form is characterized by refractions at angles of refraction 2theta of (a) 17.0°, said peak having a relative line intensity of 99, (b) 18.5°, said peak having a relative line intensity of 80, (c) 19.6°, said peak having a relative line intensity of 78 and (d) 20.7°, said peak having a relative line intensity of 100.
- the ⁇ -crystal form is characterized by refractions at angles of refraction 2theta of 13.9° (58), 17.0° (99), 17.9° (59), 18.5° (80), 19.6° (78), 20.7° (100) and 24.1 ° (62).
- the ⁇ -crystal form of the methanesulfonic acid addition salt of a compound of formula I is also characterized by a line in the X-ray diffraction diagram observed at an angle of refraction 2theta of 9.4.
- essentially pure is understood in the context of the present invention to mean especially that at least 90, preferably at least 95, and most preferably at least 99 per cent by weight of the crystals of an acid addition salt of formula I are present in the specified crystal form according to the invention, especially the ⁇ -crystal form or the ⁇ -crystal form.
- the term "essentially” means that at least the major lines of the diagram depicted in Fig. 1 , i.e. those having a relative line intensity of more than 20%, especially more than 30 %, as compared to the most intense line in the diagram, have to be present.
- the term "essentially” means that at least the major lines of the diagram depicted in Fig. 2, i.e. those having a relative line intensity of more than 20%, especially more than 30 %, as compared to the most intense line in the diagram, have to be present.
- the invention expressly relates also to those forms of the methanesulfonic acid addition salt of a compound of formula I in which crystals of the ⁇ -crystal form and/or the ⁇ -crystal form according to the invention are present in essentially pure form along with other crystal forms, in particular the ⁇ -crystal form, the ⁇ -crystal form, the H1-crystal form and/or the amorphous form of the lmatinib mesylate.
- the essentially pure methanesulfonic acid addition salt of a compound of formula I in the ⁇ -crystal form shows the X-ray diffraction diagram indicated in Fig. 1.
- the ⁇ -crystal form of the methanesulfonic acid addition salt of a compound of formula I which shows an X-ray diffraction diagram of the type shown in Fig. 1 , in which the relative peak intensities of each peak do not deviate by more than 10% from the relative peak intensities in the diagram shown in Fig. 1 , especially an X-ray diffraction diagram identical to that shown in Fig. 1.
- the essentially pure methanesulfonic acid addition salt of a compound of formula I in the ⁇ -crystal form shows the X-ray diffraction diagram indicated in Fig. 2.
- One utility of the ⁇ -crystal form and the ⁇ -crystal form of the methanesulfonic acid addition salt of a compound of formula I is the use as an intermediate for the preparation of a distinct crystal form of the methanesulfonic acid addition salt of a compound of formula I, especially the ⁇ -crystal form.
- the (preferably essentially pure) ⁇ -crystal form is obtainable by a) digesting the ⁇ -crystal form of the methanesulfonic acid addition salt of a compound of formula I with a suitable polar solvent, especially an alcohol, most especially methanol, or also a ketone (especially in a mixture with water, for example water/acetone), typically acetone, a N,N-di-lower alkyl-lower alkanecarboxamide, typically N,N-dimethylformamide or - acetamide, or a hydrophilic ether, typically dioxane, preferably in the presence of some water, or mixtures thereof, in suspension at a suitable temperature, preferably a temperature between 20 and 50 0 C, for example at about 25°C, or b) dissolving the ⁇ -crystal form of the methanesulfonic acid addition salt of a compound of formula I with a suitable polar solvent, such as especially an alcohol, typically methanol or ethanol,
- distinct crystal forms are prone to incorporate distinct impurities upon crystallization, i.e. an impurity incorporated in crystal form ⁇ is not necessarily also incorporated in the crystal form ⁇ op in the crystal form ⁇ .
- distinct crystal forms display different physical properties such as melting points, hygroscopicities, solubilities, flow properties or thermodynamic stabilities, and, hence, distinct crystal forms allow the choice of the most suitable form for a certain use or aspect, e.g. the use as an intermediate in the process of drug manufacture or in distinct administration forms like tablets, capsules, ointments or solutions.
- the ⁇ -crystal form and the ⁇ -crystal form of the methanesulfonic acid addition salt of a compound of formula I possesses valuable pharmacological properties and may, for example, be used as an anti-tumour agent or as an agent to treat restenosis.
- the present invention relates especially to the ⁇ -crystal form of the methanesulfonic acid addition salt of a compound of formula I in the treatment of one of the said diseases mentioned herein or in the preparation of a pharmacological agent for the treatment thereof.
- the present invention relates especially to the ⁇ -crystal form of the methanesulfonic acid addition salt of a compound of formula I in the treatment of one of the said diseases mentioned herein or in the preparation of a pharmacological agent for the treatment thereof.
- the antiproliferative, especially anti-tumour, activity of the methanesulfonic acid addition salt of a compound of formula I in vivo is, for example, described for the treatment of abl- dependent tumours in Nature Med. 2, 561-6 (1996).
- the invention relates also to a method for the treatment of warm-blooded animals suffering from said diseases, especially leukemia, wherein a quantity of the ⁇ -crystal form or of the ⁇ - crystal form of the methanesulfonic acid addition salt of a compound of formula I which is effective against the disease concerned, especially a quantity with antiproliferative efficacy, is administered to warm-blooded animals in need of such treatment.
- the invention relates moreover to the use of the ⁇ -crystal form or of the ⁇ -crystal form of the methanesulfonic acid addition salt of a compound of formula I for the preparation of pharmaceutical compositions for use in treating the human or animal body, especially for the treatment of tumours, such as gliomas or prostate tumours.
- the present invention relates to the use in of the ⁇ -crystal form or of the ⁇ -crystal form of the methanesulfonic acid addition salt of a compound of formula I in the treatment of one of the disorders listed below: 1. metastatic, inoperable GIST, 2. advanced chronic myeloid leukemia,
- ALL Philadelphia chromosome-positive acute lymphocytic leukemia
- glioblastoma multiforme preferably in combination with hydroxyurea
- DFSP dermatofibrosarcoma protuberans
- HES hypereosinophilic Sindrome
- CMML chronic myelomonocytic leucemia
- effective doses for example daily doses of about 50-2500 mg, preferably 100-1000 mg, especially 250-800 mg, of lmatinib mesylate having the ⁇ -crystal form or the ⁇ -crystal form are administered to warm-blooded animals of about 70 kg bodyweight.
- daily dosages of 400 mg or 600 mg are administered orally once daily, preferably together with a meal and a large glass of water (about 200 mL).
- 800 mg daily dosages are preferably administered in the form of 400 mg dosages twice daily together with food.
- the ⁇ -crystal form and the ⁇ -crystal form described herein can be utilized to prepare stable pharmaceutical dosage forms.
- the invention relates also to pharmaceutical preparations which contain an amount, especially an effective amount for prevention or treatment of one of the diseases mentioned herein, of the methanesulfonic acid addition salt of a compound of formula I in the ⁇ -crystal form or the ⁇ -crystal form, together with pharmaceutically acceptable carriers which are suitable for topical, enteral, for example oral or rectal, or parenteral administration and may be inorganic or organic and solid or liquid.
- diluents for example lactose, dextrose, sucrose, mannitol, sorbitol, cellulose, and/or glycerin
- lubricants for example silica, talc, stearic acid, or salts thereof, typically magnesium or calcium stearate, and/or polyethylene glycol, are used for oral administration.
- Tablets may likewise contain binders, for example magnesium aluminium silicate, starches, typically corn, wheat or rice starch, gelatin, methylcellulose, sodium carboxymethylcellulose and/or polyvinylpyrrolidone, and, if so desired, disintegrants, for example starches, agar, alginic acid, or a salt thereof, typically sodium alginate, and/or effervescent mixtures, or adsorbents, colouring agents, flavours, and sweetening agents.
- binders for example magnesium aluminium silicate, starches, typically corn, wheat or rice starch, gelatin, methylcellulose, sodium carboxymethylcellulose and/or polyvinylpyrrolidone, and, if so desired, disintegrants, for example starches, agar, alginic acid, or a salt thereof, typically sodium alginate, and/or effervescent mixtures, or adsorbents, colouring agents, flavours, and sweetening agents.
- Such solutions are preferably isotonic aqueous solutions or suspensions, these possibly being prepared before use, for example in the case of lyophilised preparations containing the active substance either alone or together with a carrier, for example mannitol.
- the pharmaceutical substances may be sterilised and/or may contain excipients, for example preservatives, stabilisers, wetting agents and/or emulsifiers, solubilisers, salts for the regulation of osmotic pressure, and/or buffers.
- the present pharmaceutical preparations which, if so desired, may contain further pharmacologically active substances, are prepared in a manner known per se, for example by means of conventional mixing, granulating, coating, dissolving or lyophilising processes, and contain from about 1 % to 100%, especially from about 1 % to about 20%, of the active substance or substances.
- the tablet or capsule contains 50 mg 100 mg of the of the methanesulfonic acid addition salt of a compound of formula I in the ⁇ -crystal form, optionally together with pharmaceutically acceptable carriers.
- the capsule is a hard gelatine capsule containing a dry powder blend.
- the capsule shell preferably contains gelatine and titanium dioxide as well as red iron oxide.
- the ratio of weight of capsule fill to capsule shell is preferably between about 100:25 and 100:50, more preferably between 100:30 and 100:40.
- a film coated tablet comprising 100 mg, 400 mg or 800 mg drug substance together with inactive excepients selected from colloidal anhydrous silica, polyvinylpyrrolidone, magnesium stearate and microcrystalline cellulose.
- Example 1 Preparation of crystalline form delta of lmatinib mesylate using acetone and methanol
- lmatinib mesylate About 500mg of lmatinib mesylate is first dissolved in about 100ml of water. A micro reactor is charged with about 50 ⁇ l of this aqueous solution of lmatinib mesylate. The solution is flushed with nitrogen at room temperature to dry the solution. The dry precipitate is re- suspended with about 125 ⁇ l amounts of each, acetone and methanol. The suspension is aged at about 45-55°C for about 2hrs. The solution is then allowed to evaporate at 45°C to 55°C under a stream of nitrogen.
- Example 2 Tablets with lmatinib mesylate, ⁇ -crvstal form
- Tablets containing 100 mg of the active substance named in the title are usually prepared in the following composition:
- the active substance is mixed with carrier materials and compressed on a tableting machine (Korsch EKO, punch diameter 10 mm).
- Avicel is microcrystalline cellulose (FMC, Philadelphia, USA).
- PVPPXL is polyvinylpyrrolidone, cross-linked (BASF, Germany). Aerosil is silicon dioxide (Degussa, Germany).
- Example 3 Capsules with lmatinib mesylate, ⁇ -crvstal form
- Capsules containing 100 mg of the compound named in the title as active substance are usually prepared in the following composition:
- the capsules are prepared by mixing the components and filling the mixture into hard gelatin capsules, size 1.
- Example 4 Preparation of crystalline form epsilon of lmatinib mesylate using ethyl acetate and ethanol
- lmatinib mesylate drug substance is first dissolved in about 100ml of water.
- a micro reactor is charged with about 50 ⁇ l of this aqueous solution of lmatinib mesylate.
- the solution is flushed with nitrogen at room temperature to dry the solution.
- the dry precipitate is resuspended with about 125 ⁇ l amounts of each, ethyl acetate and 95% ethanol.
- the suspension is aged at about 45-55°C for about 2hrs.
- the solution is then allowed to evaporate at 45°C to 55°C under a stream of nitrogen.
- Example 5 Tablets with lmatinib mesylate, ⁇ -crvstal form
- Tablets containing 100 mg of the active substance named in the title are usually prepared in the following composition:
- the active substance is mixed with carrier materials and compressed on a tableting machine (Korsch EKO, punch diameter 10 mm).
- Avicel is microcrystalline cellulose (FMC, Philadelphia, USA).
- PVPPXL is polyvinylpolypyrrolidone, cross-linked (BASF, Germany). Aerosil is silicon dioxide (Degussa, Germany).
- Example 6 Capsules with lmatinib mesylate, ⁇ -crvstal form
- Capsules containing 100 mg of the compound named in the title as active substance are usually prepared in the following composition:
- the capsules are prepared by mixing the components and filling the mixture into hard gelatin capsules, size 1.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Oncology (AREA)
- Hematology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicinal Preparation (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
Claims
Priority Applications (10)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN200680030515XA CN101243066B (en) | 2005-08-26 | 2006-08-24 | Delta and epsilon crystal forms of imatinib mesylate |
CA002620835A CA2620835A1 (en) | 2005-08-26 | 2006-08-24 | Delta and epsilon crystal forms of imatinib mesylate |
BRPI0615383-6A BRPI0615383A2 (en) | 2005-08-26 | 2006-08-24 | delta and epsilon crystal forms of imatinib mesylate |
JP2008527470A JP2009506014A (en) | 2005-08-26 | 2006-08-24 | Delta and epsilon crystal forms of imatinib mesylate |
EP06792999A EP1922314A1 (en) | 2005-08-26 | 2006-08-24 | Delta and epsilon crystal forms of imatinib mesylate |
MX2008002541A MX2008002541A (en) | 2005-08-26 | 2006-08-24 | Delta and epsilon crystal forms of imatinib mesylate. |
AU2006283842A AU2006283842B2 (en) | 2005-08-26 | 2006-08-24 | Delta and epsilon crystal forms of imatinib mesylate |
US12/064,637 US7879860B2 (en) | 2005-08-26 | 2006-08-24 | Delta and epsilon crystal forms of Imatinib mesylate |
IL189353A IL189353A (en) | 2005-08-26 | 2008-02-07 | Delta and epsilon crystal forms of imatinib mesylate, pharmaceutical compositions comprising them and use thereof in the preparation of medicaments for therapy |
NO20081482A NO20081482L (en) | 2005-08-26 | 2008-03-26 | Delta and epsilon crystal forms for imatinib mesylate |
Applications Claiming Priority (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US71173805P | 2005-08-26 | 2005-08-26 | |
US71173705P | 2005-08-26 | 2005-08-26 | |
US60/711,737 | 2005-08-26 | ||
US60/711,738 | 2005-08-26 | ||
US71220605P | 2005-08-29 | 2005-08-29 | |
US60/712,206 | 2005-08-29 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2007023182A1 true WO2007023182A1 (en) | 2007-03-01 |
Family
ID=37192362
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/EP2006/065662 WO2007023182A1 (en) | 2005-08-26 | 2006-08-24 | Delta and epsilon crystal forms of imatinib mesylate |
Country Status (16)
Country | Link |
---|---|
US (1) | US7879860B2 (en) |
EP (1) | EP1922314A1 (en) |
JP (1) | JP2009506014A (en) |
KR (1) | KR20080049766A (en) |
CN (2) | CN102002035B (en) |
AR (1) | AR055613A1 (en) |
AU (1) | AU2006283842B2 (en) |
BR (1) | BRPI0615383A2 (en) |
CA (1) | CA2620835A1 (en) |
EC (1) | ECSP088217A (en) |
IL (1) | IL189353A (en) |
MX (1) | MX2008002541A (en) |
MY (1) | MY148375A (en) |
NO (1) | NO20081482L (en) |
UY (1) | UY29766A1 (en) |
WO (1) | WO2007023182A1 (en) |
Cited By (24)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2007059963A1 (en) * | 2005-11-25 | 2007-05-31 | Novartis Ag | F,g,h,i and k crystal forms of imatinib mesylate |
EP1988089A1 (en) | 2006-10-26 | 2008-11-05 | Sicor, Inc. | Imatinib base, and imatinib mesylate and processes for preparation thereof |
WO2008150481A2 (en) * | 2007-05-29 | 2008-12-11 | Sicor Inc. | Processes for the preparation of crystalline form beta of imatinib mesylate |
US7550591B2 (en) | 2007-05-02 | 2009-06-23 | Chemagis Ltd. | Imatinib production process |
WO2010133976A2 (en) | 2009-05-22 | 2010-11-25 | Actavis Group Ptc Ehf | Substantially pure imatinib or a pharmaceutically acceptable salt thereof |
JP2010540465A (en) * | 2007-09-25 | 2010-12-24 | テバ ファーマシューティカル インダストリーズ リミティド | Stable imatinib composition |
WO2011023146A1 (en) | 2009-08-26 | 2011-03-03 | Zentiva, K.S. | Imatinib mesylate polymorphs generated by crystallization in aqueous inorganic salt solutions |
EP2311821A1 (en) | 2006-04-27 | 2011-04-20 | Sicor, Inc. | Polymorphic form of Imatinib mesylate and processes for its preparation |
WO2011049474A1 (en) | 2009-10-22 | 2011-04-28 | Tomasz Kozluk | Salts of imatinib with tartaric acids |
US7947699B2 (en) | 2008-01-10 | 2011-05-24 | Actavis Group Ptc Ehf | Anhydrous amorphous imatinib mesylate |
US7977348B2 (en) | 2006-04-27 | 2011-07-12 | Sicor Inc. | Polymorphic forms of imatinib mesylate and processes for preparation of novel crystalline forms as well as amorphous and form α |
WO2011095835A1 (en) | 2010-02-02 | 2011-08-11 | Actavis Group Ptc Ehf | Highly pure imatinib or a pharmaceutically acceptable salt thereof |
WO2011099039A1 (en) | 2010-02-15 | 2011-08-18 | Reliance Life Sciences Pvt. Ltd. | Process for the preparation of alpha form of imatinib mesylate |
WO2011108953A1 (en) | 2010-03-04 | 2011-09-09 | Tomasz Kozluk | PROCESS FOR PREPARATION OF POLYMORPHIC FORM α AND NEW POLYMORPHIC FORM OF IMATINIB MESYLATE ISOLATED IN THAT PROCESS |
US8067421B2 (en) | 2006-04-27 | 2011-11-29 | Sicor Inc. | Polymorphic forms of imatinib mesylate and processes for preparation of novel crystalline forms as well as amorphous and form α |
WO2011157450A1 (en) | 2010-06-18 | 2011-12-22 | Krka, D. D., Novo Mesto | New polymorphic form of imatinib base and preparation of salts thereof |
WO2012071980A1 (en) | 2010-11-30 | 2012-06-07 | 浙江九洲药业股份有限公司 | Preparation method of α-imatinib mesylate |
WO2012090221A1 (en) | 2010-12-29 | 2012-07-05 | Cadila Healthcare Limited | Novel salts of imatinib |
EP2497464A2 (en) | 2011-03-09 | 2012-09-12 | Adamed SP. Z O.O. | Pharmaceutical composition of imatinibe methanesulphonate and a process for its manufacture |
EP2604596A1 (en) * | 2011-12-16 | 2013-06-19 | Deva Holding Anonim Sirketi | Polymorphs of imatinib |
WO2013189910A1 (en) | 2012-06-22 | 2013-12-27 | Basf Se | Multicomponent crystals comprising imatinib mesilate and selected co-crystal formers |
EP2803352A1 (en) | 2013-05-14 | 2014-11-19 | Hetero Research Foundation | High dose imatinib tablets |
WO2017078647A1 (en) | 2015-11-05 | 2017-05-11 | Koçak Farma Ilaç Ve Kimya Sanayi Anonim Şirketi | Pharmaceutical compositions of imatinib |
WO2017129624A1 (en) | 2016-01-25 | 2017-08-03 | Krka, D.D., Novo Mesto | Fast dispersible pharmaceutical composition comprising tyrosine-kinase inhibitor |
Families Citing this family (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP5928159B2 (en) * | 2012-05-28 | 2016-06-01 | ニプロ株式会社 | Pharmaceutical composition |
CN105560246B (en) * | 2012-08-04 | 2019-07-26 | 正大天晴药业集团南京顺欣制药有限公司 | The preparation and its pharmaceutical composition of imatinib mesylate α crystallization |
EP3539138B1 (en) | 2016-11-11 | 2021-05-19 | Curium US LLC | Processes for generating germanium-68 with reduced volatiles |
CN112851640B (en) * | 2019-11-28 | 2023-09-01 | 广东东阳光药业股份有限公司 | Sulfate of pyrimidine benzamide compound and application thereof |
Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1999003854A1 (en) * | 1997-07-18 | 1999-01-28 | Novartis Ag | Crystal modification of a n-phenyl-2-pyrimidineamine derivative, processes for its manufacture and its use |
WO2004106326A1 (en) * | 2003-06-02 | 2004-12-09 | Hetero Drugs Limited | Novel polymorphs of imatinib mesylate |
WO2005077933A1 (en) * | 2004-02-11 | 2005-08-25 | Natco Pharma Limited | Novel polymorphic form of imatinib mesylate and a process for its preparation |
WO2005095379A2 (en) * | 2004-04-02 | 2005-10-13 | Instytut Farmaceutyczny | Crystalline methanesulfonic acid addition salts of imatinib |
WO2006024863A1 (en) * | 2004-09-02 | 2006-03-09 | Cipla Limited | Stable crystal form of imatinib mesylate and process for the preparation thereof |
WO2006048890A1 (en) * | 2004-11-04 | 2006-05-11 | Sun Pharmaceutical Industries Limited | Imatinib mesylate crystal form and process for preparation thereof |
WO2006054314A1 (en) * | 2004-11-17 | 2006-05-26 | Natco Pharma Limited | Polymorphic forms of imatinib mesylate |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5521184A (en) * | 1992-04-03 | 1996-05-28 | Ciba-Geigy Corporation | Pyrimidine derivatives and processes for the preparation thereof |
-
2006
- 2006-08-24 AU AU2006283842A patent/AU2006283842B2/en not_active Ceased
- 2006-08-24 CN CN2010105860805A patent/CN102002035B/en not_active Expired - Fee Related
- 2006-08-24 BR BRPI0615383-6A patent/BRPI0615383A2/en not_active IP Right Cessation
- 2006-08-24 CA CA002620835A patent/CA2620835A1/en not_active Abandoned
- 2006-08-24 US US12/064,637 patent/US7879860B2/en not_active Expired - Fee Related
- 2006-08-24 KR KR1020087007150A patent/KR20080049766A/en not_active Application Discontinuation
- 2006-08-24 MY MYPI20080249A patent/MY148375A/en unknown
- 2006-08-24 EP EP06792999A patent/EP1922314A1/en not_active Withdrawn
- 2006-08-24 CN CN200680030515XA patent/CN101243066B/en not_active Expired - Fee Related
- 2006-08-24 WO PCT/EP2006/065662 patent/WO2007023182A1/en active Application Filing
- 2006-08-24 MX MX2008002541A patent/MX2008002541A/en not_active Application Discontinuation
- 2006-08-24 UY UY29766A patent/UY29766A1/en not_active Application Discontinuation
- 2006-08-24 AR ARP060103680A patent/AR055613A1/en unknown
- 2006-08-24 JP JP2008527470A patent/JP2009506014A/en active Pending
-
2008
- 2008-02-07 IL IL189353A patent/IL189353A/en unknown
- 2008-02-25 EC EC2008008217A patent/ECSP088217A/en unknown
- 2008-03-26 NO NO20081482A patent/NO20081482L/en not_active Application Discontinuation
Patent Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1999003854A1 (en) * | 1997-07-18 | 1999-01-28 | Novartis Ag | Crystal modification of a n-phenyl-2-pyrimidineamine derivative, processes for its manufacture and its use |
WO2004106326A1 (en) * | 2003-06-02 | 2004-12-09 | Hetero Drugs Limited | Novel polymorphs of imatinib mesylate |
WO2005077933A1 (en) * | 2004-02-11 | 2005-08-25 | Natco Pharma Limited | Novel polymorphic form of imatinib mesylate and a process for its preparation |
WO2005095379A2 (en) * | 2004-04-02 | 2005-10-13 | Instytut Farmaceutyczny | Crystalline methanesulfonic acid addition salts of imatinib |
WO2006024863A1 (en) * | 2004-09-02 | 2006-03-09 | Cipla Limited | Stable crystal form of imatinib mesylate and process for the preparation thereof |
WO2006048890A1 (en) * | 2004-11-04 | 2006-05-11 | Sun Pharmaceutical Industries Limited | Imatinib mesylate crystal form and process for preparation thereof |
WO2006054314A1 (en) * | 2004-11-17 | 2006-05-26 | Natco Pharma Limited | Polymorphic forms of imatinib mesylate |
Cited By (38)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2007059963A1 (en) * | 2005-11-25 | 2007-05-31 | Novartis Ag | F,g,h,i and k crystal forms of imatinib mesylate |
US8198289B2 (en) | 2005-11-25 | 2012-06-12 | Novartis Ag | Crystal form H imatinib mesylate for pharmaceutical use |
EP2578580A1 (en) * | 2005-11-25 | 2013-04-10 | Novartis AG | G, I and K crystal forms of imatinib mesylate |
US8507515B2 (en) | 2005-11-25 | 2013-08-13 | Novartis Ag | Crystalline form G of imatinib mesylate |
US8592440B2 (en) | 2005-11-25 | 2013-11-26 | Novartis Ag | Crystalline form I of imatinib mesylate |
US8633213B2 (en) | 2005-11-25 | 2014-01-21 | Novartis Ag | Crystalline form F of imatinib mesylate |
US8846706B2 (en) | 2005-11-25 | 2014-09-30 | Novartis Ag | Crystalline form K of imatinib mesylate |
EP2546248A1 (en) * | 2005-11-25 | 2013-01-16 | Novartis AG | Crystal form H of imatinib mesylate |
US7893076B2 (en) | 2005-11-25 | 2011-02-22 | Novartis Ag | Crystalline form F of Imatinib mesylate |
EP2311821A1 (en) | 2006-04-27 | 2011-04-20 | Sicor, Inc. | Polymorphic form of Imatinib mesylate and processes for its preparation |
EP2829538A1 (en) | 2006-04-27 | 2015-01-28 | Sicor, Inc. | Polymorphic form of imatinib mesylate and process for its preparation |
US7977348B2 (en) | 2006-04-27 | 2011-07-12 | Sicor Inc. | Polymorphic forms of imatinib mesylate and processes for preparation of novel crystalline forms as well as amorphous and form α |
US8067421B2 (en) | 2006-04-27 | 2011-11-29 | Sicor Inc. | Polymorphic forms of imatinib mesylate and processes for preparation of novel crystalline forms as well as amorphous and form α |
EP2009008A1 (en) | 2006-10-26 | 2008-12-31 | Sicor, Inc. | Imatinib base, and imatinib mesylate and processes for preparation thereof |
EP1988089A1 (en) | 2006-10-26 | 2008-11-05 | Sicor, Inc. | Imatinib base, and imatinib mesylate and processes for preparation thereof |
US7550591B2 (en) | 2007-05-02 | 2009-06-23 | Chemagis Ltd. | Imatinib production process |
WO2008150481A3 (en) * | 2007-05-29 | 2009-01-29 | Sicor Inc | Processes for the preparation of crystalline form beta of imatinib mesylate |
WO2008150481A2 (en) * | 2007-05-29 | 2008-12-11 | Sicor Inc. | Processes for the preparation of crystalline form beta of imatinib mesylate |
JP2010540465A (en) * | 2007-09-25 | 2010-12-24 | テバ ファーマシューティカル インダストリーズ リミティド | Stable imatinib composition |
US8414918B2 (en) | 2007-09-25 | 2013-04-09 | Teva Pharmaceutical Industries Ltd. | Stable imatinib compositions |
US7947699B2 (en) | 2008-01-10 | 2011-05-24 | Actavis Group Ptc Ehf | Anhydrous amorphous imatinib mesylate |
WO2010133976A2 (en) | 2009-05-22 | 2010-11-25 | Actavis Group Ptc Ehf | Substantially pure imatinib or a pharmaceutically acceptable salt thereof |
WO2011023146A1 (en) | 2009-08-26 | 2011-03-03 | Zentiva, K.S. | Imatinib mesylate polymorphs generated by crystallization in aqueous inorganic salt solutions |
WO2011049474A1 (en) | 2009-10-22 | 2011-04-28 | Tomasz Kozluk | Salts of imatinib with tartaric acids |
WO2011095835A1 (en) | 2010-02-02 | 2011-08-11 | Actavis Group Ptc Ehf | Highly pure imatinib or a pharmaceutically acceptable salt thereof |
WO2011099039A1 (en) | 2010-02-15 | 2011-08-18 | Reliance Life Sciences Pvt. Ltd. | Process for the preparation of alpha form of imatinib mesylate |
WO2011108953A1 (en) | 2010-03-04 | 2011-09-09 | Tomasz Kozluk | PROCESS FOR PREPARATION OF POLYMORPHIC FORM α AND NEW POLYMORPHIC FORM OF IMATINIB MESYLATE ISOLATED IN THAT PROCESS |
WO2011157450A1 (en) | 2010-06-18 | 2011-12-22 | Krka, D. D., Novo Mesto | New polymorphic form of imatinib base and preparation of salts thereof |
US8871930B2 (en) | 2010-11-30 | 2014-10-28 | Zhejiang Jiuzhou Pharma Science & Technology Co., Ltd. | Preparation method of alpha-imatinib mesylate |
WO2012071980A1 (en) | 2010-11-30 | 2012-06-07 | 浙江九洲药业股份有限公司 | Preparation method of α-imatinib mesylate |
WO2012090221A1 (en) | 2010-12-29 | 2012-07-05 | Cadila Healthcare Limited | Novel salts of imatinib |
EP2497464A2 (en) | 2011-03-09 | 2012-09-12 | Adamed SP. Z O.O. | Pharmaceutical composition of imatinibe methanesulphonate and a process for its manufacture |
EP2604596A1 (en) * | 2011-12-16 | 2013-06-19 | Deva Holding Anonim Sirketi | Polymorphs of imatinib |
WO2013189910A1 (en) | 2012-06-22 | 2013-12-27 | Basf Se | Multicomponent crystals comprising imatinib mesilate and selected co-crystal formers |
US9221789B2 (en) | 2012-06-22 | 2015-12-29 | Basf Se | Multicomponent crystals comprising imatinib mesilate and selected co-crystal formers |
EP2803352A1 (en) | 2013-05-14 | 2014-11-19 | Hetero Research Foundation | High dose imatinib tablets |
WO2017078647A1 (en) | 2015-11-05 | 2017-05-11 | Koçak Farma Ilaç Ve Kimya Sanayi Anonim Şirketi | Pharmaceutical compositions of imatinib |
WO2017129624A1 (en) | 2016-01-25 | 2017-08-03 | Krka, D.D., Novo Mesto | Fast dispersible pharmaceutical composition comprising tyrosine-kinase inhibitor |
Also Published As
Publication number | Publication date |
---|---|
KR20080049766A (en) | 2008-06-04 |
AU2006283842A1 (en) | 2007-03-01 |
US20080254116A1 (en) | 2008-10-16 |
US7879860B2 (en) | 2011-02-01 |
MX2008002541A (en) | 2008-03-14 |
AR055613A1 (en) | 2007-08-29 |
ECSP088217A (en) | 2008-03-26 |
BRPI0615383A2 (en) | 2011-05-17 |
EP1922314A1 (en) | 2008-05-21 |
NO20081482L (en) | 2008-05-16 |
MY148375A (en) | 2013-04-15 |
CN102002035A (en) | 2011-04-06 |
UY29766A1 (en) | 2007-03-30 |
CN102002035B (en) | 2013-02-27 |
AU2006283842B2 (en) | 2011-03-17 |
IL189353A0 (en) | 2008-06-05 |
JP2009506014A (en) | 2009-02-12 |
CN101243066B (en) | 2012-11-14 |
CA2620835A1 (en) | 2007-03-01 |
IL189353A (en) | 2014-12-31 |
CN101243066A (en) | 2008-08-13 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US7879860B2 (en) | Delta and epsilon crystal forms of Imatinib mesylate | |
CA2628330C (en) | F,g,h,i and k crystal forms of imatinib mesylate | |
MX2008006696A (en) | F,g,h,i and k crystal forms of imatinib mesylate | |
CN101312960A (en) | F,G,H,I and K crystal forms of imatinib mesylate |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
WWE | Wipo information: entry into national phase |
Ref document number: 2006792999 Country of ref document: EP |
|
WWE | Wipo information: entry into national phase |
Ref document number: 189353 Country of ref document: IL |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2006283842 Country of ref document: AU |
|
WWE | Wipo information: entry into national phase |
Ref document number: 200680030515.X Country of ref document: CN Ref document number: 1518/DELNP/2008 Country of ref document: IN |
|
WWE | Wipo information: entry into national phase |
Ref document number: MX/a/2008/002541 Country of ref document: MX |
|
WWE | Wipo information: entry into national phase |
Ref document number: 12064637 Country of ref document: US Ref document number: 2008527470 Country of ref document: JP Ref document number: 2620835 Country of ref document: CA |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
ENP | Entry into the national phase |
Ref document number: 2006283842 Country of ref document: AU Date of ref document: 20060824 Kind code of ref document: A |
|
WWP | Wipo information: published in national office |
Ref document number: 2006283842 Country of ref document: AU |
|
WWE | Wipo information: entry into national phase |
Ref document number: 1020087007150 Country of ref document: KR |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2008111064 Country of ref document: RU |
|
WWP | Wipo information: published in national office |
Ref document number: 2006792999 Country of ref document: EP |
|
ENP | Entry into the national phase |
Ref document number: PI0615383 Country of ref document: BR Kind code of ref document: A2 Effective date: 20080227 |