Claims for Patent: 9,949,982

Summary for Patent: 9,949,982

Title:	Preparation containing cephalosporin having a catechol moiety
Abstract:	The present invention relates to a stable pharmaceutical composition comprising a compound represented by formula (I), its pharmaceutically acceptable salt or a solvate thereof. ##STR00001## The stable pharmaceutical composition can be prepared by comprising 1) a compound represented by formula (I), its pharmaceutically acceptable salt, or a solvate thereof, 2) one or more selected from the group consisting of alkali metal chlorides, alkaline earth metal chlorides, transition metal chlorides and magnesium chloride; and 3) sugar and/or a sugar alcohol.
Inventor(s):	Kawasaki; Hidenori (Osaka, JP), Kojima; Natsuko (Osaka, JP), Fujihira; Atsushi (Osaka, JP), Takahashi; Kanako (Osaka, JP), Matsubara; Fumihiko (Osaka, JP), Matsuoka; Nao (Osaka, JP)
Assignee:	Shionogi & Co., Ltd. (Osaka, JP)
Application Number:	15/508,406
Patent Claims:	1. A pharmaceutical composition comprising: 1) a compound of formula (I): ##STR00017## or pharmaceutically acceptable salt or solvate thereof; 2) one or more selected from the group consisting of alkali metal chloride, alkali earth metal chloride, transition metal chloride and magnesium chloride; and 3) a sugar and/or a sugar alcohol. 2. The pharmaceutical composition according to claim 1, wherein said component 1) is a sodium salt represented by formula (II): ##STR00018## 3. The pharmaceutical composition according to claim 1, wherein said component 1) is amorphous. 4. The pharmaceutical composition according to claim 1, which further comprises alkali metal salt, alkali earth metal salt, transition metal chloride or magnesium chloride of an organic acid or inorganic acid, or its hydrate. 5. The pharmaceutical composition according to claim 4, wherein said acid is one or more selected from the group consisting of p-toluenesulfonic acid, benzenesulfonic acid, sulfuric acid, hydrochloric acid and hydrobromic acid. 6. The pharmaceutical composition according to claim 4, wherein said acid is p-toluenesulfonic acid and/or sulfuric acid. 7. The pharmaceutical composition according to claim 4, wherein said salt is sodium salt. 8. The pharmaceutical composition according to claim 7, which comprises alkali metal chloride, wherein said alkali metal chloride is sodium chloride or potassium chloride. 9. The pharmaceutical composition according to claim 8, which comprises alkali metal chloride, wherein said alkali metal chloride is sodium chloride. 10. The pharmaceutical composition according to claim 1, which comprises alkali earth metal chloride, wherein said alkali earth metal chloride is calcium chloride. 11. The pharmaceutical composition according to claim 1, which comprises transition metal chloride, wherein said transition metal chloride is zinc chloride. 12. The pharmaceutical composition according to claim 1, wherein said sugar or sugar alcohol is one or more selected from the group consisting of monosaccharide, disaccharide and polysaccharide. 13. The pharmaceutical composition according to claim 12, wherein sugar or sugar alcohol is one or more selected from the group consisting of glucose, fructose, sucrose, mannitol and trehalose. 14. The pharmaceutical composition according to claim 12, which comprises sugar or sugar alcohol, wherein said sugar or sugar alcohol is sucrose. 15. The pharmaceutical composition according to claim 1, which comprises alkali metal chloride, and sugar or sugar alcohol, wherein said alkali metal chloride is sodium chloride, and said sugar or sugar alcohol is sucrose. 16. The pharmaceutical composition according to claim 15, which comprises sodium chloride of 0.7 to 5.0 mole equivalent as alkali metal chloride, and sucrose of 0.3 to 4.0 mole equivalent as sugar or sugar alcohol, to said component 1). 17. The pharmaceutical composition according to claim 16, which further comprises alkali metal salt of p-toluenesulfonic acid of 0.25 to 2.5 mole equivalent, and alkali metal salt of sulfuric acid of 0.05 to 2.0 mole equivalent, to said component 1). 18. The pharmaceutical composition according to claim 15, which comprises sodium chloride of 0.7 to 5.0 mole equivalent as alkali metal chloride, and sucrose of 0.3 to 4.0 mole equivalent as sugar or sugar alcohol, to the sodium salt of said component 1). 19. The pharmaceutical composition according to claim 18, which further comprises sodium p-toluenesulfonate of 0.25 to 2.5 mole equivalent, and of sodium sulfate of 0.05 to 2.0 mole equivalent, to the sodium salt of said component 1). 20. The pharmaceutical composition according to claim 16, wherein an increased amount of a compound represented by formula (III): ##STR00019## in said pharmaceutical composition is less than 0.4% from starting of storage at 40.degree. C. for two weeks. 21. The pharmaceutical composition according to claim 16, wherein the increased amount of the compound represented by formula (III) in said pharmaceutical composition is less than 0.05% from starting of storage at 25.degree. C. for two weeks. 22. The pharmaceutical composition according to claim 16, wherein an increased amount of a compound represented by formula (IV): ##STR00020## in said pharmaceutical composition is less than 0.05% from starting of storage at 25.degree. C. for two weeks. 23. The pharmaceutical composition according to claim 21, wherein an increased amount of a compound represented by formula (IV) ##STR00021## in said pharmaceutical composition is less than 0.05% from starting of storage at 25.degree. C. for two weeks. 24. The pharmaceutical composition according to claim 1, which further comprises sodium gluconate. 25. A pharmaceutical composition comprising: component 1) a compound of formula (I): ##STR00022## and its pharmaceutically acceptable salt or solvate thereof, wherein an increased amount of a compound represented by formula (III): ##STR00023## in said pharmaceutical composition is less than 0.4% from starting of storage at 40.degree. C. for two weeks. 26. A pharmaceutical composition comprising: component 1) a compound of formula (I): ##STR00024## or pharmaceutically acceptable salt or solvate thereof, wherein the increased amount of the compound represented by formula (III): ##STR00025## in said pharmaceutical composition is less than 0.05% from starting of storage at 25.degree. C. for two weeks. 27. A pharmaceutical composition comprising: component 1) a compound of formula (I): ##STR00026## or pharmaceutically acceptable salt or solvate thereof, wherein the increased amount of the compound represented by formula (IV): ##STR00027## in said pharmaceutical composition is less than 0.05% from starting of storage at 25.degree. C. for two weeks. 28. A pharmaceutical composition comprising: component 1) a compound of formula (I): ##STR00028## or pharmaceutically acceptable salt or solvate thereof, wherein the increased amount of the compound represented by formula (III): ##STR00029## in said pharmaceutical composition is less than 0.05%, and the increased amount of the compound represented by formula (IV): ##STR00030## in said pharmaceutical composition is less than 0.05% from starting of storage at 25.degree. C. for two weeks. 29. The pharmaceutical composition according to claim 1, which is a lyophilized product. 30. The pharmaceutical composition according to claim 1, which is an injectable composition. 31. A method of manufacturing a pharmaceutical preparation, comprising: a) a step of adjusting a pH of a liquid comprising a compound represented by formula (I): ##STR00031## or pharmaceutically acceptable salt or a solvate thereof to pH 5 to 6 with alkali materials; b) a step of mixing the liquid prepared by said step a) with: one or more selected from a group consisting of alkali metal chloride, alkali earth metal chloride, transition metal chloride and magnesium chloride; and a sugar and/or a sugar alcohol; and c) a step of lyophilizing the mixture prepared by said step b). 32. The method of manufacturing the pharmaceutical preparation according to claim 31, wherein said alkali material is sodium hydroxide. 33. A pharmaceutical composition prepared by the method of manufacturing the pharmaceutical preparation according to claim 31. 34. A method of manufacturing a pharmaceutical preparation, comprising: a) a step of adjusting a pH of a suspension comprising a compound represented by formula (I): ##STR00032## or pharmaceutically acceptable salt or a solvate thereof to pH 5 to 6 with alkali materials; b) a step of mixing the suspension prepared by said step a) with: one or more selected from a group consisting of alkali metal chloride, alkali earth metal chloride, transition metal chloride and magnesium chloride; and a sugar and/or a sugar alcohol; and c) a step of lyophilizing the mixture prepared by said step b). 35. The method of manufacturing the pharmaceutical preparation according to claim 34, wherein said alkali material is sodium hydroxide. 36. A pharmaceutical composition prepared by the method of manufacturing the pharmaceutical preparation according to claim 34.