WO2010089768A2 - Pharmaceutical composition - Google Patents
Pharmaceutical composition Download PDFInfo
- Publication number
- WO2010089768A2 WO2010089768A2 PCT/IN2010/000015 IN2010000015W WO2010089768A2 WO 2010089768 A2 WO2010089768 A2 WO 2010089768A2 IN 2010000015 W IN2010000015 W IN 2010000015W WO 2010089768 A2 WO2010089768 A2 WO 2010089768A2
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- composition
- solution
- pharmaceutical composition
- tromethamine
- bortezomib
- Prior art date
Links
- HCSFPFDGDYVJDD-ABLWVSNPSA-N CC(C)C[C@@H](B(O)O)NC(C(Cc1ccccc1)N)=O Chemical compound CC(C)C[C@@H](B(O)O)NC(C(Cc1ccccc1)N)=O HCSFPFDGDYVJDD-ABLWVSNPSA-N 0.000 description 1
Classifications
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- 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
- A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
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- 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
- A61K31/13—Amines
- A61K31/133—Amines having hydroxy groups, e.g. sphingosine
-
- 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
- A61K31/69—Boron compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/05—Dipeptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Definitions
- the present invention relates to a novel parenteral pharmaceutical composition
- a novel parenteral pharmaceutical composition comprising N-(2-pyrazine) carbonyl-L-phenylalanine-L-leucine boronic acid and tromethamine.
- Such composition in lyophilized dry form is stable at room temperature and upon reconstitution forms aqueous solutions that are stable for at least 12 hours.
- Bortezomib is N-(2-pyrazine) carbonyl-L-phenylalanine-L-leucine boronic acid.
- Solid bortezomib is not soluble at a concentration of lmg/ml in 0.9 % w/v of sodium chloride. It is commercially available under the trade name of Velcade for injection. It is given intravenously only and contains mannitol ester of bortezomib. It is available in a lyophilized form which when reconstituted forms a solution consisting of the mannitol ester in equilibrium with bortezomib. Velcade ® is reconstituted with 0.9 % sodium chloride to a final concentration of 1 mg/ml of bortezomib. The use of mannitol provides the desired solubility.
- United States patent US 6,713,446 describes that bortezomib is known to be stable for more than 2 years when stored at -2 0 C to - 20 0 C, as determined by HPLC analysis (purity > 97 %). But when stored at 2 0 C - 8 0 C, the product is not stable for longer than 3-6 months.
- United States Patent US 6,713,446 (hereinafter referred to '446) provides a stable, pharmaceutically acceptable composition comprising bortezomib.
- the claims of the patent encompass the commercially available Velcade ® for injection.
- patent '3117 discloses a method for reducing the rate of degradation of proteins in an animal comprising contacting cells of the animal with certain boronic ester and acid compounds. Also disclosed are novel boronic ester and acid compounds, their synthesis and uses.
- novel boronic ester and acid compounds can be converted to their basic salts by mixing a solution of a boronic acid (Z ' and Z 2 are both OH) of the invention with a solution of a pharmaceutically acceptable non-toxic base, such as, sodium hydroxide, potassium hydroxide, sodium bicarbonate, sodium carbonate, or an amino compound, such as choline hydroxide, Tris, bis-Tris, N-methylglucamine or arginine. Water-soluble salts are preferable.
- alkaline metal salts sodium, potassium etc.
- alkaline earth metal salts magnesium, calcium etc.
- ammonium salts and salts of pharmaceutically acceptable amines tetramethylammonium, triethylamine, methylamine, dimethylamine, cyclopentylamine, benzylamine, phenethylamine, piperidine monoethanolamine, diethanolamine, tris(hydroxymethyl)amine, lysine, arginine and N-methyl-D-glucamine).
- the inventors also identified that the problems of instability of the pharmaceutical composition in dry form as well as in a reconstituted form was connected to the impurity levels present in the bulk of the bortezomib. For instance, when bortezomib' bulk with total impurity levels of about 3 %, was used for preparing the injectable composition, the pH when adjusted to 7.6-8.4, the composition remained stable for desired period whereas when the bulk of bortezomib having total impurity levels less than 0.51 % was utilized, the pH of the composition when adjusted to a pH of about 6.8 - 8.2, the composition remained stable for desired period.
- the present invention provides a parenteral pharmaceutical composition comprising therapeutically effective amount of N-(2-pyrazine) carbonyl-L-phenylalanine-L-leucine boronic acid or its salts or its derivative and tromethamine wherein the composition is stable.
- the present invention also provides a method for formulating a therapeutically effective amount of N-(2- pyrazine) carbonyl-L-phenylalanine-L-leucine boronic acid or its salts or its derivatives, said the method comprising steps of:
- the present invention particularly, provides a pharmaceutical composition
- a pharmaceutical composition comprising therapeutically effective amounts of bortezomib or its salt or its derivatives and tromethamine wherein the pH of the said composition is in the range of 6.8 to 8.4, preferably 7.0 to 8.2.
- the present invention still further provides a lyophilized pharmaceutical composition comprising therapeutically effective amounts of bortezomib and tromethamine wherein the pH of the said composition is in the range of 6.8 to 8.4, preferably 7.0 to 8.2.
- lyophilized composition refers to any solid material obtained by lyophilization or freeze drying of an aqueous mixture. It may be also referred to as freeze dried mass.
- stable composition any composition having sufficient stability to have utility as a pharmaceutical agent.
- the formulation has sufficient stability to allow storage at a convenient temperature, preferably between O 0 C and 4O 0 C, for a reasonable period of time, preferably longer than one month, more preferably longer than three months, even more preferably longer than six months, and most preferably longer than one year.
- the term 'stable composition' as used herein means that the pharmaceutical composition when in the form of a lyophilized cake or powder that is the composition is not reconstituted, remains unaltered in terms of physical and chemical parameters for a prolonged period of time when packed in container which are either protected or unprotected against light, under various storage conditions.
- the pharmaceutical composition of the present invention remains stable for 6 months.
- the pharmaceutical composition when reconstituted with a suitable reconstitution medium such as water for injection the reconstituted solution is said to be stable when there is no significant chemical degradation for at least 12 hours, preferably 24 hours and there are no signs of precipitation or appearance of particles in the clear solution on storage at room temperature for the said time.
- the parenteral pharmaceutical composition upon reconstitution remains stable for at least 12 hours, preferably 24 hours and the total impurities in the clear solution are found to be less than 0.68 at 1 month when stored at 40° C and 75 % relative humidity.
- the pharmaceutical composition of the present invention is free of any added preservatives. It was surprisingly found that the composition in either dry form or after reconstitution, in- spite of being preservative free, the composition remained stable for longer period of time i.e if in the dry form, the composition remained stable for 6 months at ambient temperature or if reconstituted with a suitable reconstitution media, for at least 24 hours, preferably 12 hours. It is very important that the reconstituted composition remains physically and chemically stable during the period of administration. Usually, this reconstituted composition may be administered to the patients along with other active ingredients either intravenously or by oral administration. Generally, the reconstituted composition of the present invention is administered as a bolus intravenous injection.
- the present invention provides a stable pharmaceutical composition comprising therapeutically effective amounts of N-(2-pyrazine) carbonyl-L-phenylalanine-L-leucine boronic acid or its salts or its derivatives and tromethamine wherein the pH of the said composition is in the range of 6.8 to 8.4, preferably 7.0 to 8.2.
- the present invention provides a lyophilized pharmaceutical composition
- a lyophilized pharmaceutical composition comprising therapeutically effective amount of N-(2-pyrazine) carbonyl-L-phenylalanine-L-leucine boronic acid or its salts or its derivatives and tromethamine wherein the pH of the said composition is in the range of 6.8 to 8.4, preferably 7.0 to 8.2.
- the present invention also provides a pharmaceutical composition
- a pharmaceutical composition comprising therapeutically effective amounts of N-(2-pyrazine) carbonyl-L-phenylalanine-L-leucine boronic acid or its salts or its derivatives and tromethamine wherein the pH of the composition is in the range of 7.6 to 8.4, preferably 7.9 to 8.1.
- the present invention provides a lyophilized pharmaceutical composition
- a lyophilized pharmaceutical composition comprising therapeutically effective amounts of N-(2-pyrazine) carbonyl-L-phenylalanine-L-leucine boronic acid or its salts or its derivatives and tromethamine wherein the pH of the composition is in the range of 7.6 to 8.4, preferably 7.9 to 8.1.
- the inventors further identified that the stability problems and the solution to this problem is associated with the source of the bortezomib that is employed in the preparation of the parenteral pharmaceutical composition of the present invention.
- the source of the bortezomib that is employed in the preparation of the parenteral pharmaceutical composition of the present invention.
- the pH of the composition was adjusted to a pH of about 6.8-8.2, the composition remained stable for desired period. Therefore, not only the active pharmaceutical ingredient, but the type and amount of the impurities present in it, seemed to play a role in the achieving the stability of the dry as well as reconstituted composition.
- the bortezomib bulk (API) used in the present invention can be synthesized by various synthetic ways.
- the inventors found that when the bortezomib having a specific optical rotation of about - 53.4°, residual solvent content of less than 100 ppm and total impurities less than 0.51% and known identified impurity such as impurity B were less than about 0.1 % and impurity H were is less than about 0.04 % and any single maximum unknown impurity was less than 0.11 %, an injectable composition comprising such a source of bortezomib could be prepared by adjusting the pH of the solution in the range of about 7.0 to about 7.5. However, when bortezomib of any other grade which does not satisfy these limits of impurities was employed, it was found that a stable injectable composition could be prepared by adjusting the pH in the range of about 7.9 to about 8.4.
- Impurity A chiral isomer: [ (lR)-3-methyl-l- [[ (2S) -l-oxo-3-phenyl-2- [ (pyrazinylcarbonyl) amino] propyl ]amino]butyl] boronic acid
- Impurity H 3-phenyl-2-[(pyrazine-2-carbomy) amino]-propionionainide
- Impurity B L-phenylalanine-L-leucine boronic acid
- Impurity I 3-phenyl-2-[ (pyrazine-2-carbomyl)amino]-propionic acid
- the pharmaceutical composition comprises therapeutically effective amounts of N-(2-pyrazine) carbonyl- L-phenylalanine-L-leucine boronic acid or its salts or its derivatives.
- the amount of bortezomib in the pharmaceutical composition of the present invention ranges from about O.lmg/ml to about 5 mg/ml, preferably about 0.5 mg/ml to about 2 mg/ml and most preferably, about 1 mg/ml.
- the pharmaceutical composition comprises tromethamine which is chemically known as 2-amino-2- (hydroxymethyl) propane-1, 3-diol. Particularly, a parenteral grade or a USP complying grade of tromethamine is suitable for the pharmaceutical composition.
- the amount of tromethamine in the pharmaceutical composition of the present invention ranges from about 0.1 mg/ ml to about 5 mg/ml, preferably about 0.5 mg/m] to about 2 mg/ml and most preferably, about 1 mg/ml. It was observed that for one mole of bortezomib about 3 moles of tromethamine gave satisfactory solubility to bortezomib.
- the solution may additionally comprise of acid, such as for example, hydrochloric acid to adjust to pH of the composition to a desirable range. It is critical that the pH of the solution is adjusted in the range of 7.6 to 8.4. It was found that when the pH of the composition was adjusted beyond the specified range, there was presence of particles indicating precipitation of bortezomib and/or there was difficulty on the reconstitution of the lyophilized cake. Quick and complete reconstitution of the lyophilized cake was found when the pH of the composition was adjusted in the range of 6.8 to 8.2, preferably in the range of 7.0 to 8.1.
- acid such as for example, hydrochloric acid
- the IR spectrum of the lyophilized composition according to Example 1 and Example 2 of the present invention were recorded and is given in Figure 1 and Figure 2.
- the IR spectroscopy of the composition shows a strong B-N bond indicating formation of tromethamine salt of bortezomib. It may be said without wishing to be bound by any theory, that the completion of salt formation may be important in the quicker reconstitution of the lyophilized cake.
- the preferred pharmaceutical composition may be readily reconstituted in about 30 seconds. By the term readily means without the application of any external energy such as sonication. Simple swirling or movement of the container in which the composition is stored for reconstituting the cake or powdery mass is also meant to be readily reconstituted.
- the composition may include, tonicity adjusting agents, bulking agents and the like and mixtures thereof.
- tonicity adjusting agents include, but are not limited to, sodium chloride, mannitol, lactose, sucrose, maltose, trehalose and the like and mixtures thereof.
- sodium chloride is used as a tonicity adjusting agent and/or bulking agent.
- the amount of sodium chloride that may be used in the pharmaceutical composition of the present invention includes, but is not limited to, 0 mg to about 100 mg per ml of the solution, preferably about 15 mg to 45 mg of the solution. Any other suitable tonicity agent such as sugar, sugar alcohols may also be employed.
- the present invention provides a lyophilized pharmaceutical composition
- a lyophilized pharmaceutical composition comprising therapeutically effective amounts of bortezomib wherein the source of bortezomib used has total impurities of about 2.5 % and tromethamine, wherein the pH of the composition is in the range of 7.6 to 8.4, preferably 7.9 to 8.1.
- the present invention provides lyophilized pharmaceutical composition
- lyophilized pharmaceutical composition comprising therapeutically effective amounts of bortezomib wherein the bortezomib source used has total impurities of about 0.5 % and tromethamine, wherein the pH of the composition is in the range of 6.8 to 8.4, preferably 7.0 to 8.1.
- a bulking agent may be added in the composition.
- the term "bulking agent” is intended to mean a compound used to add bulk to the lyophilized product and/or assist in the control of the properties of the formulation during lyophilization.
- bulking agents examples include, but are not limited to, dextran, trehalose, sucrose, polyvinylpyrrolidone, sodium chloride, lactose, inositol, sorbitol, albumin, calcium lactobionate and others known to those of ordinary skill in the art.
- the composition may include apart from tonicity adjusting agents, bulking agent, cryoprotectants.
- cryoprotectants include, but are not limited to, carbohydrates such as monosaccharides, disaccharides and sugar alcohols.
- carbohydrates such as monosaccharides, disaccharides and sugar alcohols.
- the carbohydrates include, but are not limited to, mannitol, sucrose and others known to those of ordinary skill in the art.
- the pharmaceutical composition of the present invention may be prepared by simply mixing the required amounts of N-(2-pyrazine) carbonyl-L-phenylalanine-L-leucine boronic acid and tromethamine and adding water for injection with continuous stirring.
- the solution may be warmed at 45 0 C to 50 0 C to form a clear solution.
- the solution may then be filtered through 0.2 to 0.8 micron syringe filter, preferably 0.45 micron filter and then the pH is determined.
- the pH of the clear solution is further adjusted with hydrochloric acid in the range of 7.6 to 8.4, preferably in the range of 7.9 to 8.1.
- the pH adjusted clear solution may be subjected to lyophilization or freeze drying.
- the lyophilization involves two steps namely, thermal treatment step wherein no vacuum is applied and the actual primary drying step wherein vacuum is applied.
- the solution subjected to lyophilization is filled into vials with specialized stoppers.
- the vials filled with the solution to be dried are placed in the lyophilizer.
- temperature of shelf of lyophilizer where the vials of solution filled is stored, is gradually decreased from 20 0 C to - 40 0 C.
- the frozen solution is subjected to drying step.
- the temperature is set from - 40 ° C to - 15 ° C for the time cycle of about 5 to 6 hours at a vacuum of about 100 to 200 mTorr.
- the ice is dried. Then the temperature of the material is raised to + 10 ° C to about + 25 ° C at a vacuum of about 50 mTorr in which the residual solvent if any is removed.
- the lyophilized composition or commonly referred to as lyophilized cake in the vials may then be subjected to reconstitution at the time of administration.
- the reconstitution of the lyophilized cake of the pharmaceutical composition of the present invention takes less than 90 seconds without any need of bath-sonication. Also, the reconstituted solution was found to be stable in terms of particle formation for at least 12 hours i.e no particulates were observed and also was chemically stable.
- Bortezomib (3.5 mg) having total impurity of about 2.75 % was used in this composition.
- the bulk of bortezomib was accurately weighed and taken in a 5 ml vial.
- Tromethamine (3.31 mg) was weighed and mixed in the vial.
- Water for injection (quantity sufficient to make 1 ml) was added with continuous stirring.
- the solution was warmed at 45 0 C to 50 0 C to form a clear solution.
- the solution was cooled and 30 mg of sodium chloride was added to the cooled solution.
- the solution was filtered through 0.45 micron syringe filter and the pH was determined.
- the pH of the clear solution was 8.63 which was adjusted with 1 % hydrochloric acid to 7.28.
- the clear solution was lyophilized.
- the reconstitution of the lyophilized cake took more than 120 seconds. After reconstitution, the solution was found to be unstable in terms of particle formation for 24 hours i.e particulates were observed
- the pH of the clear solution was 8.68 which was adjusted with 5 % hydrochloric acid to 8.01.
- the clear solution was lyophilized.
- the reconstitution of the lyophilized cake took less than 30 seconds . without any need of bath sonication. After reconstitution, the solution was found to be stable in terms of particle formation for 24 hours i.e no particulates were observed.
- the IR spectrum of the lyophilized composition was recorded. The IR spectrum is given in Figure 1.
- the IR spectroscopy of the formula indicates formation of tromethamine salt having a strong B-N bond.
- the reconstitution of the lyophilized cake took less than 30 seconds without any need of bath sonication. After reconstitution, the solution was found to be stable in terms of particle formation for 24 hours i.e no particulates were observed.
- the IR spectrum of the lyophilized composition was recorded. The IR spectrum is given in Figure 2. The IR spectroscopy of the formula indicates formation of tromethamine salt having a strong B-N bond.
- the volume was made up and then the solution was filtered through 0.2-0.8 micron syringe filter.
- the clear solution was lyophilized in the vials.
- the lyophilized cake was stored in vials at various stability conditions and was subjected to the chemical and physical stability. The results of the stability are tabulated below.
- Table 3 a Physical stability of the reconstituted solution of the lyoph ⁇ ized cake of example IV
- the volume was made up and then the solution was filtered through 0.2-0.8 micron syringe filter.
- the clear solution was lyophilized in the vials.
- the lyophilized cake was stored in vials at various stability conditions and was subjected to the chemical and physical stability. The results of the stability are tabulated below.
- the lyophilized cake in the vials was reconstituted with 3.5 ml of water for injection. The reconstitution was quick and took less than 90 seconds. The final reconstituted solution was clear. This reconstituted solution was stored at 2 0 C to 8 0 C for a period of 48 hours. The reconstituted solution was also subjected to storage temperatures of 20 0 C to 25 0 C. The stored solution was analyzed for related substances i.e unknown impurities and total impurities and the bortezomib content.
- the assay and the impurities were determined by HPLC. The solutions were found to be stable over a period of 48 hours.
- Table 5b Chemical stability of the reconstituted solution of the lyophilized cake of example IV filled in vials (V) and syringe (S)
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- Animal Behavior & Ethology (AREA)
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- Veterinary Medicine (AREA)
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- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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- Gastroenterology & Hepatology (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Description
Claims
Priority Applications (8)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
MX2011007192A MX2011007192A (en) | 2009-01-09 | 2010-01-08 | Bortezumib containing pharmaceutical composition. |
EA201170921A EA201170921A1 (en) | 2009-01-09 | 2010-01-08 | PHARMACEUTICAL COMPOSITION |
CA2748921A CA2748921A1 (en) | 2009-01-09 | 2010-01-08 | Bortezumib containing pharmaceutical composition |
JP2011544969A JP5689816B2 (en) | 2009-01-09 | 2010-01-08 | Parenteral pharmaceutical composition and method for producing the parenteral pharmaceutical composition |
AU2010211981A AU2010211981A1 (en) | 2009-01-09 | 2010-01-08 | Bortezumib containing pharmaceutical composition |
CN2010800041181A CN102292086B (en) | 2009-01-09 | 2010-01-08 | Pharmaceutical composition |
US13/143,808 US9095514B2 (en) | 2009-01-09 | 2010-01-08 | Pharmaceutical composition |
EP10738286.3A EP2379077A4 (en) | 2009-01-09 | 2010-01-08 | Pharmaceutical composition |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IN58MU2009 | 2009-01-09 | ||
IN58/MUM/2009 | 2009-01-09 |
Related Child Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US13/143,808 A-371-Of-International US9095514B2 (en) | 2009-01-09 | 2010-01-08 | Pharmaceutical composition |
US14/750,496 Continuation US20150290277A1 (en) | 2009-01-09 | 2015-06-25 | Pharmaceutical composition |
Publications (2)
Publication Number | Publication Date |
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WO2010089768A2 true WO2010089768A2 (en) | 2010-08-12 |
WO2010089768A3 WO2010089768A3 (en) | 2010-11-04 |
Family
ID=42542466
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/IN2010/000015 WO2010089768A2 (en) | 2009-01-09 | 2010-01-08 | Pharmaceutical composition |
Country Status (10)
Country | Link |
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US (1) | US9095514B2 (en) |
EP (1) | EP2379077A4 (en) |
JP (1) | JP5689816B2 (en) |
KR (1) | KR20110114562A (en) |
CN (1) | CN102292086B (en) |
AU (1) | AU2010211981A1 (en) |
CA (1) | CA2748921A1 (en) |
EA (1) | EA201170921A1 (en) |
MX (1) | MX2011007192A (en) |
WO (1) | WO2010089768A2 (en) |
Cited By (11)
Publication number | Priority date | Publication date | Assignee | Title |
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US8263578B2 (en) | 2010-03-18 | 2012-09-11 | Innopharma, Inc. | Stable bortezomib formulations |
CN103070835A (en) * | 2013-01-31 | 2013-05-01 | 江苏奥赛康药业股份有限公司 | Freeze-dried composition containing bortezomib and preparation method of freeze-dried composition |
JP2013522320A (en) * | 2010-03-18 | 2013-06-13 | イノファーマ,インコーポレイテッド | Stable bortezomib formulation |
EP2644189A1 (en) | 2012-03-27 | 2013-10-02 | Innopharma, Inc. | Stable bortezomib formulations |
CN103720666A (en) * | 2013-12-16 | 2014-04-16 | 亿腾药业(泰州)有限公司 | Preparation method for bortezomib freeze-dried preparation for injection |
US8962572B2 (en) | 2010-10-05 | 2015-02-24 | Fresenius Kabi Usa, Llc | Bortezomib formulations |
EA021179B1 (en) * | 2012-06-15 | 2015-04-30 | Ощество С Ограниченной Ответственностью "Тева" | Lyophilisate of a compound of boronic acid |
EP3031811A1 (en) | 2014-12-09 | 2016-06-15 | Teva Pharmaceuticals Ltd. | Malic acid esters of bortezomib |
WO2016110870A1 (en) | 2015-01-07 | 2016-07-14 | Emcure Pharmaceuticals Limited | Pharmaceutical composition of bortezomid |
EP3164137A4 (en) * | 2014-07-04 | 2018-01-10 | Dr. Reddy's Laboratories Ltd. | Stable liquid ready-to-use injectable formulation of bortezomib |
RU2659160C1 (en) * | 2017-07-10 | 2018-06-28 | Акционерное Общество "Фарм-Синтез" | Bortezomib lyophilizate production method and the bortezomib containing pharmaceutical composition in the form of stable lyophilizated product produced by said method |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2866135A1 (en) * | 2012-03-02 | 2014-09-06 | Dr. Reddy's Laboratories Limited | Pharmaceutical compositions comprising boronic acid compounds |
CN104586776B (en) * | 2013-10-30 | 2017-05-17 | 扬子江药业集团上海海尼药业有限公司 | Preparation taking bortezomib as active composition and preparation method thereof |
US10765665B2 (en) * | 2015-11-24 | 2020-09-08 | Melin Jeffrey | Composition comprising combination of rapamycin and an activator of AMP kinase and use thereof for treating diseases |
KR101807462B1 (en) | 2017-03-09 | 2017-12-08 | 씨제이헬스케어 주식회사 | Stable formulation comprising bortezomib, and its preparation method |
JP7423028B2 (en) * | 2017-11-01 | 2024-01-29 | 日医工岐阜工場株式会社 | Lyophilized pharmaceutical composition containing bortezomib |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6617317B1 (en) | 1994-10-28 | 2003-09-09 | Millennium Pharmaceuticals, Inc. | Boronic ester and acid compositions |
WO2006001965A2 (en) | 2004-05-24 | 2006-01-05 | Abgenix, Inc. | Reducing the risk of human anti-human antibodies through v gene manipulation |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2002059131A1 (en) * | 2001-01-25 | 2002-08-01 | Millennium Pharmaceuticals, Inc. | Formulation of boronic acid compounds |
US20060084592A1 (en) * | 2002-09-09 | 2006-04-20 | Trigen Limited | Peptide boronic acid inhibitors |
WO2006001956A2 (en) * | 2004-05-20 | 2006-01-05 | The Board Of Trustees Of The University Of Illinois | Compositions for inhibiting cell growth and inducing apoptosis in cancer cells and methods of use thereof |
CN101795671A (en) | 2007-08-21 | 2010-08-04 | 阿尔扎公司 | Liposome compositions for in vivo administration of boronic acid compounds |
-
2010
- 2010-01-08 CA CA2748921A patent/CA2748921A1/en not_active Abandoned
- 2010-01-08 JP JP2011544969A patent/JP5689816B2/en not_active Expired - Fee Related
- 2010-01-08 US US13/143,808 patent/US9095514B2/en not_active Expired - Fee Related
- 2010-01-08 MX MX2011007192A patent/MX2011007192A/en not_active Application Discontinuation
- 2010-01-08 EA EA201170921A patent/EA201170921A1/en unknown
- 2010-01-08 CN CN2010800041181A patent/CN102292086B/en not_active Expired - Fee Related
- 2010-01-08 EP EP10738286.3A patent/EP2379077A4/en not_active Withdrawn
- 2010-01-08 AU AU2010211981A patent/AU2010211981A1/en not_active Abandoned
- 2010-01-08 KR KR1020117015778A patent/KR20110114562A/en not_active Application Discontinuation
- 2010-01-08 WO PCT/IN2010/000015 patent/WO2010089768A2/en active Application Filing
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6617317B1 (en) | 1994-10-28 | 2003-09-09 | Millennium Pharmaceuticals, Inc. | Boronic ester and acid compositions |
WO2006001965A2 (en) | 2004-05-24 | 2006-01-05 | Abgenix, Inc. | Reducing the risk of human anti-human antibodies through v gene manipulation |
Non-Patent Citations (2)
Title |
---|
SARA WU ET AL., J.PHARM. SCI, vol. 89, 2000, pages 758 - 765 |
See also references of EP2379077A4 |
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US9061037B2 (en) | 2010-03-18 | 2015-06-23 | Innopharma, Inc. | Stable bortezomib formulations |
US9180093B2 (en) | 2010-03-18 | 2015-11-10 | Innopharma, Inc. | Stable bortezomib formulations |
JP2013522320A (en) * | 2010-03-18 | 2013-06-13 | イノファーマ,インコーポレイテッド | Stable bortezomib formulation |
US8263578B2 (en) | 2010-03-18 | 2012-09-11 | Innopharma, Inc. | Stable bortezomib formulations |
US9107821B2 (en) | 2010-03-18 | 2015-08-18 | Innopharma, Inc. | Stable bortezomib formulations |
US8962572B2 (en) | 2010-10-05 | 2015-02-24 | Fresenius Kabi Usa, Llc | Bortezomib formulations |
EP2644189A1 (en) | 2012-03-27 | 2013-10-02 | Innopharma, Inc. | Stable bortezomib formulations |
EA021179B1 (en) * | 2012-06-15 | 2015-04-30 | Ощество С Ограниченной Ответственностью "Тева" | Lyophilisate of a compound of boronic acid |
CN103070835A (en) * | 2013-01-31 | 2013-05-01 | 江苏奥赛康药业股份有限公司 | Freeze-dried composition containing bortezomib and preparation method of freeze-dried composition |
CN103720666A (en) * | 2013-12-16 | 2014-04-16 | 亿腾药业(泰州)有限公司 | Preparation method for bortezomib freeze-dried preparation for injection |
EP3164137A4 (en) * | 2014-07-04 | 2018-01-10 | Dr. Reddy's Laboratories Ltd. | Stable liquid ready-to-use injectable formulation of bortezomib |
EP3031811A1 (en) | 2014-12-09 | 2016-06-15 | Teva Pharmaceuticals Ltd. | Malic acid esters of bortezomib |
WO2016110870A1 (en) | 2015-01-07 | 2016-07-14 | Emcure Pharmaceuticals Limited | Pharmaceutical composition of bortezomid |
RU2659160C1 (en) * | 2017-07-10 | 2018-06-28 | Акционерное Общество "Фарм-Синтез" | Bortezomib lyophilizate production method and the bortezomib containing pharmaceutical composition in the form of stable lyophilizated product produced by said method |
Also Published As
Publication number | Publication date |
---|---|
EP2379077A2 (en) | 2011-10-26 |
CA2748921A1 (en) | 2010-08-12 |
JP2012514633A (en) | 2012-06-28 |
EP2379077A4 (en) | 2013-09-11 |
CN102292086B (en) | 2013-05-08 |
JP5689816B2 (en) | 2015-03-25 |
US9095514B2 (en) | 2015-08-04 |
MX2011007192A (en) | 2011-10-04 |
US20110275597A1 (en) | 2011-11-10 |
CN102292086A (en) | 2011-12-21 |
KR20110114562A (en) | 2011-10-19 |
AU2010211981A1 (en) | 2011-08-18 |
EA201170921A1 (en) | 2012-01-30 |
WO2010089768A3 (en) | 2010-11-04 |
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