WO2008023807A1 - Composition pharmaceutique stabilisée - Google Patents
Composition pharmaceutique stabilisée Download PDFInfo
- Publication number
- WO2008023807A1 WO2008023807A1 PCT/JP2007/066495 JP2007066495W WO2008023807A1 WO 2008023807 A1 WO2008023807 A1 WO 2008023807A1 JP 2007066495 W JP2007066495 W JP 2007066495W WO 2008023807 A1 WO2008023807 A1 WO 2008023807A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- pharmaceutical composition
- vitamin
- compound
- sodium
- composition according
- Prior art date
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Classifications
-
- 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
-
- 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
- A61K31/4965—Non-condensed pyrazines
- A61K31/497—Non-condensed pyrazines containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/20—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
-
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Definitions
- the present invention relates to sodium carbazochrome sulfonate and derivatives thereof, vitamin C, peptide hydroxyanisole, vitamin E, vitamin P, gallic acid, propyl gallate, alpha-glycerin, and cysteine hydrochloride.
- 1_ (2-methoxyethyl) -2-methyl-4,9-dioxo-3- (pyrazine-2-ylmethyl) -4, characterized by containing one or more selected from the group consisting of , 9-dihydro-1H-naphtho [2,3-d] imidazol-3-ium (hereinafter abbreviated as Compound A) or a pharmaceutically acceptable salt thereof, and lyophilized product thereof Product and stabilization method.
- the chloride of Compound A is hygroscopic and unstable with respect to humidity, such as increased degradation during long-term storage, but the bromide of Compound A is not hygroscopic and has storage stability. Since it is good, it is also reported that it is useful as a drug manufacturing base (see Patent Document 2).
- Patent Document 1 International Publication No. 01/60803 Pamphlet
- Patent Document 2 International Publication No. 04/92160 Pamphlet
- antitumor agents trade name: dacarbazine Note; Kyowa Hakko Kogyo
- vitamin preparations trade name: K2
- Eisa is the product name Vitaject; Terumo), and is currently shielded from light by physical methods during storage and administration.
- nitroprusside is sitafloxacin
- light-stabilized injections see, for example, JP-A 7-126017 and WO01080858.
- taercetin, ascorbic acid, gallic acid, sodium carbazochrome sulfonate, butylhydroxyanisole, 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid are more stable.
- the photostabilization effect of taercetin, ascorbic acid, gallic acid, butylhydroxyanisole, 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid The possibility of a correlation with radical scavenging ability was suggested.
- composition according to claim 1 comprising one or more selected from the group consisting of sodium carbazochrome sulfonate and derivatives thereof, vitamin Cs, and butylhydroxyanisole,
- composition according to claim 1 characterized in that it contains sodium carbazochrome sulfonate and its derivatives,
- a pharmaceutical composition obtainable by lyophilizing the pharmaceutical composition according to claims 1 to 6,
- composition of the present invention is described in detail below.
- the pharmaceutically acceptable salt of Compound A in the present invention is not particularly limited, but it does not have hygroscopicity as a manufacturing base and is stored for a long period of time. Bromide with stability is preferred.
- the liquid pharmaceutical composition of the present invention is not particularly limited as long as it is a liquid pharmaceutical composition. More specifically, it can be used not only for systemic administration such as injectable pharmaceutical compositions including infusions and liquid pharmaceutical compositions for oral use, but also for topical administration such as sprays.
- Strength A preferred form of the pharmaceutical composition of the present invention is an injectable pharmaceutical composition, more specifically, an injectable pharmaceutical composition for intramuscular or intravenous administration.
- the pharmaceutical composition of the present invention also includes a lyophilized product that is appropriately dissolved in a physiological saline solution before administration and prepared so as to have an appropriate concentration described later.
- the compounding amount of Compound A in the liquid pharmaceutical composition of the present invention is not particularly limited, but considering the therapeutic method as an anticancer agent in the clinical trials so far, for example, 0.01 mg / ml or more
- the power of being an aqueous solution of Compound A 0.01 mg / ml to lOOmg / ml is preferred, O.Olmg / ml to 5 mg / ml is more preferred 0.05 mg / ml to lmg / ml is particularly preferred 0.05
- Most preferred is an aqueous solution of Compound A at a concentration of mg / ml to 0.5 mg / ml.
- the administration method of the liquid pharmaceutical composition of the present invention is not particularly limited, but continuous intravenous administration for 7 days by infusion or the like is considered. Such long-term administration is not preferable in view of the stability of Compound A after opening the liquid pharmaceutical composition or after preparing the lyophilized product to be dissolved. In view of prevention, it is preferable to avoid changing the chemical solution for as long as possible. Therefore, more specifically, the pharmaceutical composition of the present invention can be administered intravenously by infusion or the like over 4 hours or more, preferably 10 hours or more, more preferably 15 hours or more. Particularly preferably, it is administered intravenously by infusion or the like over 24 hours.
- the pharmaceutical composition of the present invention is a liquid pharmaceutical composition after being opened or freeze-dried. It can be said that it is preferable that the composition is stable over the above-mentioned time after the preparation of dissolution.
- the light stabilizer of compound A contained in the liquid pharmaceutical composition of the present invention includes vitamins C, butylhydroxyanisole, vitamins E, vitamins P, gallic acid and gallic acid pills, Examples include alpha thioglycerin and cysteine hydrochloride, and derivatives thereof.
- Preferred are vitamin C, butylhydroxyanisole, vitamin E, vitamin P, gallic acid, propyl gallate and derivatives thereof, more preferably vitamin C, butylhydroxyanisole and derivatives thereof. It is.
- One or more of these light stabilizers can be used in combination as appropriate.
- vitamin C examples include ascorbyl palmitate, ascorbate stearate, and erythorbic acid.
- vitamin E 6-hydroxy-2,5,7,8-tetramethylchroman ⁇ 2-Carboxylic acid (trade name Trolox), ⁇ - ⁇ -tocopherol, d- ⁇ -tocopherol, tocoinole, and tocotrienol.
- Vitamins ⁇ include taercetin, rutin and Flavonoids are mentioned.
- the compounding amount of the light stabilizer with respect to the above-mentioned compound ⁇ is dissolved in water or water to which a solubilizing agent such as ethanol is added, and exhibits the stabilizing effect of compound A.
- the weight ratio of the stabilizer to compound A is 1.3 to 13 parts by weight for alphathioglycerin, 1 to 10 parts by weight for cystine hydrochloride, and vitamin C.
- 0.02 to 20 parts by weight preferably 0.2 to 20 parts by weight for vitamin E, 0.25 to 2.5 parts by weight for vitamins E, 0.000 to 0.4 to 0.4 parts by weight for vitamins, preferably 0.04 to 0.4 parts by weight, 0.04 to 4 parts by weight for butylhydroxylazole, preferably 0.4 to 4 parts by weight, 0.005 to 5 parts by weight for gallic acid or propyl gallate, preferably 0.05 to 5 parts by weight.
- examples of the light stabilizer of compound ⁇ ⁇ contained in the liquid pharmaceutical composition of the present invention include sodium carbazochrome sulfonate and derivatives thereof.
- examples of the derivative of sodium carbazochrome sulfonate include carbazochrome and adrenochrome monoaminoguanidine methanesulfonate.
- Sodium carbazochrome sulfonate is particularly stable under long-term storage conditions because it has low reactivity with compound A itself and there is no change in formulation, and is most preferred as the stabilizer of the present invention.
- the compounding amount of sodium carbazochrome sulfonate and its derivative in the pharmaceutical composition of the present invention is 0.01 parts by weight or more with respect to Compound A, and considering the stabilization effect after dilution to the clinical administration concentration. More preferably, it is 0.05 parts by weight or more, particularly preferably in the range of 0.1 to 1.0 part by weight, and most preferably in the range of 0.2 to 0.5 part by weight. In consideration of the pre-use examples, it is 20 parts by weight or less, preferably 0.5 parts by weight or less. In addition, the above-mentioned stabilizers can be used as appropriate by combining one or more kinds.
- Acid buffer or pH adjuster, isotonic agent, and light mentioned in the claims of the present invention Dissolve one or more stabilizers in water for injection so that the final concentration in the drug solution is the desired concentration, and then add an appropriate amount of an alkaline pH adjuster to adjust the pH to make an acidic buffer solution for drug solution preparation. Dissolve the raw material of Compound A in this solution, add an appropriate amount of water for injection, and adjust the total volume to a predetermined volume. After filling this drug solution in a sealed container, perform an appropriate sterilization method, or perform an appropriate aseptic operation and fill the sealed container to make a liquid pharmaceutical composition of Compound A.
- lactic acid, citrate, phosphoric acid, tartaric acid, dilute hydrochloric acid or the like can be used as an acidic buffer or acidic pH adjuster.
- an isotonizing agent sodium chloride, magnesium chloride, sodium bromide, fructose, lactose, glucose, D-sorbitol, nicotinamide, and the like can be used.
- the alkaline pH adjuster is not particularly limited as long as it is an alkaline substance used for a pH adjuster used as a pharmaceutical, such as sodium hydroxide, magnesium hydroxide, potassium hydroxide.
- the order of addition of the Compound A drug substance and the stabilizer of the present invention is not limited to this procedure.
- an appropriate solubilization method may be used when a necessary amount of the light stabilizer listed in the claims of the present invention is added.
- the solubilizer include ethanol, propylene glycol, concentrated glycerin, polyethylene glycol, dimethylacetamide, polysorbate, polyoxyethylene hydrogenated castor oil, and cyclodextrin.
- Additives such as soothing agents such as lucol, mepiva hydrochloride hydrochloride, xylocaine hydrochloride, lidocaine, preservatives such as benzyl alcohol, methyl parabenzoate, propyl parabenzoate, ethanolamide of gentisic acid, thimerosal, chlorobutanol can be added depending on the S.
- additives such as hydrophilic low molecules such as glucose, sodium chloride, glycine and mannitol can be added as necessary to alleviate local toxicity (see, for example, JP-A-11-193233).
- the liquid pharmaceutical composition of the present invention may be lyophilized by adding a physiologically acceptable excipient.
- the excipient is not particularly limited as long as it usually enhances the moldability of a lyophilized product.
- saccharides such as mannitol, inositol, maltose, sucrose, ratatose, cyclodextrin, dextran 40, glycine, Examples include amino acids such as alanine, norin and methionine.
- Such a lyophilized preparation is appropriately prepared by dissolving in physiological saline or the like before administration to a patient.
- the pharmaceutical composition of the present invention has excellent compoundability with electrolyte solutions such as physiological saline and glucose infusions, saccharide infusions, and other infusions, and can be used in combination with these infusions. It is.
- FIG. 1 shows the relationship between various stabilizers and radical scavenging ability.
- Taercetin was dissolved in ethanol. Further, 3 mL of the stabilizer solution was mixed with 3 mL of the composition of Comparative Example 1 (Compound A 10 mg / mL), added to a white glass container, and stoppered and tightened. 1 pharmaceutical composition was obtained.
- Ascorbic acid was dissolved in a 9 mg / mL lactic acid solution, and an appropriate amount of sodium hydroxide solution was added to adjust the pH to 3.6. Further, 3 mL of the stabilizer solution was mixed with 3 mL of the comparative pharmaceutical composition of Comparative Example 1 (Compound A 10 mg / mL), added to a white glass container, and stoppered and wound. The pharmaceutical composition of Example 2 was obtained.
- Example 4 After gallic acid was dissolved in ethanol, an appropriate amount of a sodium hydroxide solution was added to a 9 mg / mL lactic acid solution in advance and dissolved in a lactic acid buffer adjusted to pH 3.6. Furthermore, 3 mL of the stabilizer solution was mixed with 3 mL of the comparative pharmaceutical composition (Compound A 10 mg / mL) of Comparative Example 1 above, added to a white glass container, and then plugged and tightened. The pharmaceutical composition of Example 3 was obtained.
- Example 4 Example 4
- Example 4 Except that ascorbic acid of Example 2 was replaced with sodium canolevasochrome sulfonate, The pharmaceutical composition of Example 4 was obtained in the same manner as Example 2.
- Example 5 A pharmaceutical composition of Example 5 was obtained in the same manner as in Example 1 except that taercetin in Example 1 was replaced with butylhydroxylazole.
- Example 6 The pharmaceutical composition of Example 6 in the same manner as in Example 1 except that taercetin in Example 1 was replaced with 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid. I got a thing.
- Example 7 A pharmaceutical composition of Example 7 was obtained in the same manner as in Example 2, except that ascorbic acid of Example 2 was replaced with cysteine hydrochloride.
- Example 8 A pharmaceutical composition of Example 8 was obtained in the same manner as in Example 2, except that ascorbic acid in Example 2 was replaced with alphathioglycerin.
- Table 1 shows the stabilizer used in Comparative Example 2 and Examples 1 to 8, the weight ratio (parts by weight) of the stabilizer relative to Compound A, and the amount of the photodegradation product.
- Compound A chemical solution (5mg / mL) was added with a predetermined amount of stabilizer, and after irradiation with D65 lamp / 1000 lux light for 24 hours, the amount of photodegradation was measured. Under the experimental conditions, 3.4% photodegradation product was produced.
- some compounds have no light stabilizing effect, and the combined power Taercetin, ascorbic acid, gallic acid, sodium carbazochrome sulfonate, and butylhydroxyl. When nisol and 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid were added, the formation of photodegradation products was suppressed and a photostabilization effect was observed.
- DPPH 1, 1-diphenyl-2-picrylhydrazyl
- Figure 1 shows the results plotted for each sample solution, with the vertical axis representing the stabilization rate during the photostability test and the horizontal axis representing the radical scavenging ability.
- ascorbic acid gallic acid
- butinorehydroxyanisole 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid The possibility was suggested.
- the stabilizers of the present invention having a high photostabilizing effect, it was considered to have excellent stability and particularly low reactivity with the compound A! /, (No change in formulation! /) Further studies were conducted on sodium carbazochrome sulfonate.
- Comparative Example 4 and Example 9 were stored upside-down for 168 hours at room temperature under white fluorescent lamp / 1000 lux conditions, and the residual ratio of Compound A was measured to evaluate the stability. Compound A in each solution was quantified using HPLC.
- Compound A remaining rate (%) (Compound A concentration 5 mg / mL diluted in physiological saline)
- Example 10 After diluting the pharmaceutical composition of Compound A of Comparative Example 1 to a final concentration of 0.1 mg / mL with physiological saline to which a predetermined amount of sodium carbazochrome sulfonate shown in Table 3 was added, In addition to the colored glass container, the stopper was wound and tightened to obtain the pharmaceutical composition of Example 10.
- Comparative Example 4 and Examples 10 to 12 were stored in an inverted state for 168 hours under the condition of white fluorescent light / 1000 lux at room temperature, and the residual ratio of Compound A was measured to evaluate the stability.
- the volume of each sample solution was determined using HPLC.
- Example 10 in which the weight ratio of sodium carbazochrome sulfonate to Compound A was 0.05, the residual rate was 95% at 15 hours, and the residual rate at 24 hours was 93%, both of which were not added. And improved light stability.
- Example 11 In the case of Example 11 in which the concentration was further increased and the weight ratio of sodium carbazochrome sulfonate to compound A was 0.5, the residual rate at 15 hours was 99%, and the residual rate at 24 hours was 98%.
- Example 12 in which the weight ratio of sodium carbazochrome sulfonate to compound A was 25 at a high concentration, there was almost no change in the residual rate at 15 hours and 24 hours.
- the technical feature of the present invention is that 1_ (2-methoxyethyl) -2-methyl-4,9-dioxo-3- (pyrazin-2-ylmethyl) -4,9-dihydro-1H-naphtho
- a liquid pharmaceutical composition of 2,3-d] imidazole-3-ium or a pharmaceutically acceptable salt thereof the composition itself is stabilized by combining with a specific compound. Since it has become possible to provide a liquid pharmaceutical composition that is stable over time, it has a significant industrial effect, particularly when it is continuously administered for a long period of time after the preparation is opened.
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Description
Claims
Priority Applications (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US12/377,461 US20100249413A1 (en) | 2006-08-25 | 2007-08-24 | Stabilized pharmaceutical composition |
CA002661618A CA2661618A1 (en) | 2006-08-25 | 2007-08-24 | Stabilized pharmaceutical composition |
JP2008530975A JPWO2008023807A1 (ja) | 2006-08-25 | 2007-08-24 | 安定化された医薬組成物 |
EP07806081A EP2055304A1 (en) | 2006-08-25 | 2007-08-24 | Stabilized pharmaceutical composition |
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2006-229203 | 2006-08-25 | ||
JP2006229203 | 2006-08-25 | ||
JP2007066340 | 2007-08-23 | ||
JPPCT/JP2007/066340 | 2007-08-23 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2008023807A1 true WO2008023807A1 (fr) | 2008-02-28 |
Family
ID=39106889
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/JP2007/066495 WO2008023807A1 (fr) | 2006-08-25 | 2007-08-24 | Composition pharmaceutique stabilisée |
Country Status (5)
Country | Link |
---|---|
US (1) | US20100249413A1 (ja) |
EP (1) | EP2055304A1 (ja) |
JP (1) | JPWO2008023807A1 (ja) |
CA (1) | CA2661618A1 (ja) |
WO (1) | WO2008023807A1 (ja) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US11753476B2 (en) | 2018-04-08 | 2023-09-12 | Cothera Bioscience, Inc. | Combination therapy for cancers with BRAF mutation |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN104800172B (zh) * | 2015-05-26 | 2017-08-29 | 成都天台山制药有限公司 | 注射用卡络磺钠粉针剂和制法 |
CN105434371A (zh) * | 2015-12-29 | 2016-03-30 | 江苏吴中医药集团有限公司 | 一种卡络磺钠冻干粉针剂及其制备方法 |
CN110680807B (zh) * | 2019-08-01 | 2021-07-13 | 广东健信制药股份有限公司 | 一种注射用棓丙酯的制备方法 |
CN110960493B (zh) * | 2019-12-30 | 2022-03-11 | 山东罗欣药业集团股份有限公司 | 一种帕瑞昔布钠冻干制剂及其制备方法 |
CN116158429A (zh) * | 2021-11-25 | 2023-05-26 | 沈阳中化农药化工研发有限公司 | 一种含有联苯类化合物稳定的液体制剂 |
Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH07126017A (ja) | 1993-10-26 | 1995-05-16 | Maruishi Seiyaku Kk | ニトロプルシドナトリウム水溶液の沈殿防止及び安定化方法 |
JPH11193233A (ja) | 1997-10-16 | 1999-07-21 | Yamanouchi Pharmaceut Co Ltd | 注射剤 |
WO2001060803A1 (fr) * | 2000-02-15 | 2001-08-23 | Yamanouchi Pharmaceutical Co., Ltd. | Derives d'imidazolium fondus |
WO2001080858A1 (fr) | 2000-04-24 | 2001-11-01 | Daiichi Pharmaceutical Co., Ltd. | Preparation liquide stable |
JP2003128548A (ja) * | 2001-08-10 | 2003-05-08 | Yamanouchi Pharmaceut Co Ltd | 縮合イミダゾリウム誘導体を含む医薬組成物 |
WO2004092160A1 (ja) | 2003-04-15 | 2004-10-28 | Astellas Pharma Inc. | 臭化物及びその結晶 |
-
2007
- 2007-08-24 US US12/377,461 patent/US20100249413A1/en not_active Abandoned
- 2007-08-24 EP EP07806081A patent/EP2055304A1/en not_active Withdrawn
- 2007-08-24 JP JP2008530975A patent/JPWO2008023807A1/ja not_active Withdrawn
- 2007-08-24 CA CA002661618A patent/CA2661618A1/en not_active Abandoned
- 2007-08-24 WO PCT/JP2007/066495 patent/WO2008023807A1/ja active Application Filing
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH07126017A (ja) | 1993-10-26 | 1995-05-16 | Maruishi Seiyaku Kk | ニトロプルシドナトリウム水溶液の沈殿防止及び安定化方法 |
JPH11193233A (ja) | 1997-10-16 | 1999-07-21 | Yamanouchi Pharmaceut Co Ltd | 注射剤 |
WO2001060803A1 (fr) * | 2000-02-15 | 2001-08-23 | Yamanouchi Pharmaceutical Co., Ltd. | Derives d'imidazolium fondus |
WO2001080858A1 (fr) | 2000-04-24 | 2001-11-01 | Daiichi Pharmaceutical Co., Ltd. | Preparation liquide stable |
JP2003128548A (ja) * | 2001-08-10 | 2003-05-08 | Yamanouchi Pharmaceut Co Ltd | 縮合イミダゾリウム誘導体を含む医薬組成物 |
WO2004092160A1 (ja) | 2003-04-15 | 2004-10-28 | Astellas Pharma Inc. | 臭化物及びその結晶 |
Non-Patent Citations (6)
Title |
---|
BYOIN YAKUGAKU, vol. 9, no. 6, 1983, pages 498 - 504 * |
DATABASE CAPLUS [online] GOTO K.: "Characteristics changes of injection formulations. 4. Incompatibility of latamoxef sodium injection", XP003020288, Database accession no. (1984:428158) * |
KOSHIRO A.: "Cefotiam no Haigoekichu ni Okeru Anteisei", JOURNAL OF PHARMACEUTICAL SCIENCE AND TECHNOLOGY, JAPAN, vol. 42, no. 4, 1982, pages 370 - 376, XP003020286 * |
OKANO S.: "Shin. Yakuzaigaku Soron", vol. 3RD ED., 10 April 1987, HAKKO, NANKODO CO., LTD., pages: 359 - 361, XP003020285 * |
TAKEUCHI TOKUO ET AL.: "Studies on the DPPH Radical Scavenging ability of Miso", BULLETIN OF GIFU WOMEN'S COLLEGE, vol. 33, 2004, pages 115 - 122 |
YAMAJI A.: "Stability of ritodrine hydrochloride in infusion solution", JAPANESE JOURNAL OF PHARMACEUTICAL HEALTH AND CARE AND SCIENCES, vol. 13, no. 5, 1987, pages 298 - 303, XP003020287 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US11753476B2 (en) | 2018-04-08 | 2023-09-12 | Cothera Bioscience, Inc. | Combination therapy for cancers with BRAF mutation |
Also Published As
Publication number | Publication date |
---|---|
CA2661618A1 (en) | 2008-02-28 |
US20100249413A1 (en) | 2010-09-30 |
EP2055304A1 (en) | 2009-05-06 |
JPWO2008023807A1 (ja) | 2010-01-14 |
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