Novel pharmaceutical composition containing hydroxamic acid derivative or salt thereof

2:

• The pharmaceutical composition according to claim 1, wherein the solubilizing agent is a cyclodextrin or a cyclodextrin derivative.

3:

• The pharmaceutical composition according to claim 1, wherein the hydroxamic acid derivative is (2S)-2-((4-((4-((1S)-1,2-dihydroxyethyl)phenyl)ethynyl)benzoyl)(methyl)amino)-N-hydroxy-N′,2-dimethylmalonamide.

4:

• The pharmaceutical composition according to claim 2, wherein the cyclodextrin or the cyclodextrin derivative is one or more selected from the group consisting of α-cyclodextrin, γ-cyclodextrin, hydroxypropyl-α-cyclodextrin, sulfobutylether-β-cyclodextrin, 2,3,6-tri-O-methyl-β-cyclodextrin, hydroxyethyl-β-cyclodextrin, hydroxypropyl-β-cyclodextrin, heptakis-2,6-di-O-methyl-β-cyclodextrin, 6-O-α-maltosyl-β-cyclodextrin, methyl-β-cyclodextrin and hydroxypropyl-γ-cyclodextrin.

5:

• The pharmaceutical composition according to claim 2, wherein the cyclodextrin or the cyclodextrin derivative is one or more selected from the group consisting of α-cyclodextrin, γ-cyclodextrin, hydroxypropyl-α-cyclodextrin, sulfobutylether-β-cyclodextrin, hydroxypropyl-β-cyclodextrin and hydroxypropyl-γ-cyclodextrin.

6:

• The pharmaceutical composition according to claim 1, wherein the pharmaceutical composition is a liquid formulation.

7:

• The pharmaceutical composition according to claim 6, wherein a pH of the liquid formulation is from 3 to 8.

8:

• The pharmaceutical composition according to claim 1, wherein the pharmaceutical composition is a frozen liquid formulation.

9:

• The pharmaceutical composition according to claim 8, wherein a pH of the frozen liquid formulation when thawed is from 3 to 8.

10:

• The pharmaceutical composition according to claim 1, wherein the pharmaceutical composition is a lyophilized formulation.

11:

• The pharmaceutical composition according to claim 10, wherein a pH of an aqueous solution of the lyophilized formulation is from 3 to 8.

12:

• The pharmaceutical composition according to claim 1, wherein the solubilizing agent is one or more selected from the group consisting of monoalcohols, polyhydric alcohols, amides, sulfoxides, amino acids, surfactants, acids and bases.

13:

• The pharmaceutical composition according to claim 12, wherein the hydroxamic acid derivative is (2S)-2-((4-((4-((1S)-1,2-dihydroxyethyl)phenyl)ethynyl)benzoyl)(methyl)amino)-N-hydroxy-N′,2-dimethylmalonamide.

14:

• The pharmaceutical composition according to claim 12, wherein the monoalcohol is an alcohol having 1 to 6 carbon atoms;
• the polyhydric alcohol is a diol;
• and the acid is an organic acid.

15:

• The pharmaceutical composition according to claim 12, wherein the solubilizing agent is one or more selected from the group consisting of alcohols having 1 to 6 carbon atoms, diols, amino acids and organic acids in combination with an amide.

16:

• The pharmaceutical composition according to claim 12, wherein the pharmaceutical composition is a liquid formulation.

17:

• A method of inhibiting LpxC, comprising administering the pharmaceutical composition according to claim 1 to a subject in need thereof.

18:

• A method of inhibiting Gram-negative bacteria, comprising administering the pharmaceutical composition according to claim 1 to a subject in need thereof.

19:

• A method for producing a liquid formulation comprising a hydroxamic acid derivative or a salt thereof and a solubilizing agent, the method comprising:
• dissolving the hydroxamic acid derivative selected from the group consisting of (2S)-2-((4-((4-((1S)-1,2-dihydroxyethyl)phenyl)ethynyl)benzoyl)(methyl)amino)-N-hydroxy-N′,2-dimethylmalonamide, (2S)-2-((4-((4-((1R)-1,2-dihydroxyethyl)phenyl)ethynyl)benzoyl)(methyl)amino)-N-hydroxy-N′,2-dimethylmalonamide and (2S)—N-hydroxy-2-((4-((4-((1S)-1-hydroxy-2-methoxyethyl)phenyl)ethynyl)benzoyl)(methyl)amino)-N′,2-dimethylmalonamide, or the salt thereof, and the solubilizing agent in water to obtain an aqueous solution of the hydroxamic acid derivative or the salt thereof,
• followed by adjusting a pH of the obtained aqueous solution to 3 to 8.

20:

• The production method according to claim 19, wherein the solubilizing agent is a cyclodextrin or a cyclodextrin derivative.

21:

• The production method according to claim 19, wherein the hydroxamic acid derivative is (2S)-2-((4-((4-((1S)-1,2-dihydroxyethyl)phenyl)ethynyl)benzoyl)(methyl)amino)-N-hydroxy-N′,2-dimethylmalonamide.

22:

• The production method according to claim 20, wherein the cyclodextrin or the cyclodextrin derivative is one or more selected from the group consisting of α-cyclodextrin, γ-cyclodextrin, hydroxypropyl-α-cyclodextrin, sulfobutylether-β-cyclodextrin, 2,3,6-tri-O-methyl-β-cyclodextrin, hydroxyethyl-β-cyclodextrin, hydroxypropyl-β-cyclodextrin, heptakis-2,6-di-O-methyl-β-cyclodextrin, 6-O-α-maltosyl-β-cyclodextrin, methyl-β-cyclodextrin and hydroxypropyl-γ-cyclodextrin.

23:

• The production method according to claim 20, wherein the cyclodextrin or the cyclodextrin derivative is one or more selected from the group consisting of α-cyclodextrin, γ-cyclodextrin, hydroxypropyl-α-cyclodextrin, sulfobutylether-β-cyclodextrin, hydroxypropyl-β-cyclodextrin and hydroxypropyl-γ-cyclodextrin.