Takeda Chemical Industries, Inc.

Takeda Pharmaceutical Company Limited

Masayoshi Kaneko

Shigeo Yabuno

Kenji Iwaoka

Hidetoshi Nishimura

Kenji c/o Takeda Pharmaceutical Company Limited Iwaoka

A method of producing an oxidized compound is disclosed. An electric potential is measured of an oxidation reaction solution for producing an oxidized compound by an oxidation reaction, and an end point is determined of the oxidation reaction on the basis of a predefined decrease of the electric potential. Preferably, after the electric potential of the oxidation reaction solution is reached to a highest electric potential, a point is determined where the amount of an electric potential dropped from the highest electric potential reaches the predefined amount of an electric potential as the end point of the oxidation reaction. The method also may introduce an oxidation reaction terminating agent to the oxidation reaction solution immediately after determining the end point of the oxidation reaction.

Method and apparatus for producing oxidized compound

The instant invention describes a method of producing a crystal of an imidazole compound or a salt thereof, which comprises suspending a solvate of the imidazole compound into a solution containing water, alcohol, and a basic substance.

Method of producing a crystal of an imidazole compound

A method of crystallizing (1R,5S,6S)-2-[(6,7-dihydro-5H-pyrazolo[1,2-a][1,2,4]triazolium-6-yl)]thio- 6-[(R)-1-hydroxyethyl]-1-methyl-carbapenem-3-carboxylate (hereinafter simply referred to as L-627), which is characterized by maintaining an aqueous solution of L-627 at temperatures ranging from the eutectic temperature of the solution to temperatures lower than 0.degree. C. The method provides some advantages that loss of L-627 accompanied by crystallization is less, number of steps in the preparation of vial formulations is less and maintenance of these steps under sterile and dust-free conditions can be performed easily, dispensation of the drug can be conducted with quantitative accuracy, and the crystals dissolve in a solvent promptly at the time of use.

Production of crystalline penem

A method of crystallizing (1R,5S,6S)-2-[(6,7-dihydro-5H-pyrazolo[1,2-a][1,2,4]triazolium-6-yl)]thio- 6[(R)-1-hydroxyethyl]-1-methyl-carbapenem-3-carboxylate (hereinafter simply referred to as L-627), which is characterized by maintaining an aqueous solution of L-627 at temperatures ranging from the eutectic temperature of the solution to temperatures lower than 0.degree. C. The method provides some advantages that loss of L-627 accompanied by crystallization is less, number of steps in the preparation of vial formulations is less and maintenance of these steps under sterile and dust-free conditions can be performed easily, dispensation of the drug can be conducted with quantitative accuracy, and the crystals dissolve in a solvent promptly at the time of use.

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Hyogo, Japan

Masayoshi Kaneko