Injection preparation and method for producing same

An injection preparation comprising:

• an aqueous composition;
• and
• a container which encloses the aqueous composition,
• wherein the aqueous composition contains the following (i) to (iii), and
• wherein the ratio of the number of oxygen molecules with respect to the number of pemetrexed molecules in the injection preparation is less than or equal to 0.0025:
• (i) pemetrexed or a salt thereof;
• (ii) at least one antioxidant agent which is selected from the group consisting of ascorbic acid, an ascorbic acid derivative, and salts thereof, and the content of which is 0.0001 mass % to 0.5 mass % with respect to the total mass of the aqueous composition in terms of ascorbic acid;
• and
• (iii) an aqueous solvent of greater than or equal to 50 mass % with respect to the total mass of the aqueous composition.

A method for producing an injection preparation, comprising:

• producing an aqueous composition which contains:
• (i) pemetrexed or a salt thereof,
• (ii) at least one antioxidant agent which is selected from the group consisting of ascorbic acid, an ascorbic acid derivative, and salts thereof, and the content of which is 0.0001 mass % to 0.5 mass % with respect to the total mass of the aqueous composition in terms of ascorbic acid, and
• (iii) an aqueous solvent of greater than or equal to 50 mass % with respect to the total mass of the aqueous composition;
• and
• filling the container with the aqueous composition under an inert gas atmosphere or substituting gas within a container with inert gas after filling the container with the aqueous composition.

An injection preparation comprising:

• an aqueous composition containing the following (i) to (iv);
• and
• a container which encloses the aqueous composition,
• wherein the concentration of oxygen in gas within the container which encloses the aqueous composition is less than or equal to 1.5 volume %:
• (i) pemetrexed or a salt thereof;
• (ii) at least one antioxidant agent A which is selected from the group consisting of ascorbic acid, an ascorbic acid derivative, and salts thereof, and the content of which is 0.001 mass % to 1.0 mass % with respect to the total mass of the aqueous composition in terms of ascorbic acid;
• (iii) at least one antioxidant agent B which is selected from the group consisting of a compound having a thiol group or a salt thereof, and a compound having a sulfide bond or a salt thereof, and the content of which is 0.00050 mass % to 0.15 mass % with respect to the total mass of the aqueous composition;
• and
• (iv) an aqueous solvent of greater than or equal to 50 mass % with respect to the total mass of the aqueous composition.

An injection preparation comprising:

• an aqueous composition;
• and
• a container which encloses the aqueous composition,
• wherein the aqueous composition contains the following (i) to (iv), and
• wherein the ratio of the number of oxygen molecules with respect to the number of pemetrexed molecules in the injection preparation is less than or equal to 0.0120:
• (i) pemetrexed or a salt thereof;
• (ii) at least one antioxidant agent A which is selected from the group consisting of ascorbic acid, an ascorbic acid derivative, and salts thereof, and the content of which is 0.001 mass % to 1.0 mass % with respect to the total mass of the aqueous composition in terms of ascorbic acid;
• (iii) at least one antioxidant agent B which is selected from the group consisting of a compound having a thiol group or a salt thereof, and a compound having a sulfide bond or a salt thereof, and the content of which is 0.00050 mass % to 0.15 mass % with respect to the total mass of the aqueous composition;
• and
• (iv) an aqueous solvent of greater than or equal to 50 mass % with respect to the total mass of the aqueous composition.

A method for producing an injection preparation, comprising:

• producing an aqueous composition which contains:
• (i) pemetrexed or a salt thereof,
• (ii) at least one antioxidant agent A which is selected from the group consisting of ascorbic acid, an ascorbic acid derivative, and salts thereof, and the content of which is 0.001 mass % to 1.0 mass % with respect to the total mass of the aqueous composition in terms of ascorbic acid,
• (iii) at least one antioxidant agent B which is selected from the group consisting of a compound having a thiol group or a salt thereof, and a compound having a sulfide bond or a salt thereof, and the content of which is 0.00050 mass % to 0.15 mass % with respect to the total mass of the aqueous composition, and
• (iv) an aqueous solvent of greater than or equal to 50 mass % with respect to the total mass of the aqueous composition;
• and
• filling the container with the aqueous composition under an inert gas atmosphere or substituting gas within a container with inert gas after filling the container with the aqueous composition.