JPH0443074B2 - - Google Patents

Description

[Detailed description of the invention]

(Objective of the invention) Industrial application field This invention relates to a freeze-dried powder of fosmidomycin or its salts and a method for producing the same, and provides a technology useful for the chemical industry such as pharmaceuticals and agricultural chemicals. . Conventional technology Fosmidomycin has the general formula [3-(N-formyl-N-hydroxyamino)
Propylphosphonic acid] is a known substance with excellent antibacterial activity, and its salts include, for example, sodium salt,
Salts with inorganic or organic bases such as potassium salts, calcium salts, aluminum salts, ammonium salts, magnesium salts, triethylamine salts, ethanolamine salts, dicyclohexylamine salts, ethylene diane salts, N,N'-dibenzylethylene diamine salts, Salts with basic amino acids such as arginine salts are known. (For example, JP-A-53-
(Refer to Publication No. 40720) Problems to be Solved by the Invention Incidentally, when producing freeze-dried powder for intradermal preparations, for example, even if one tries to obtain freeze-dried powder from an aqueous solution of fosmidomycin or its salts, If the amount of fosmidomycin or its salts is small, a water-containing film will form on the wall of the vial, and even if the amount is relatively large, only a foamed solid will be obtained, resulting in a freeze-dried powder. I couldn't get it. Therefore, the inventors first aimed to obtain a freeze-dried powder of fosmidomycin or its salts, and further aimed to obtain a stable freeze-dried powder of fosmidomycin or its salts. purpose. (Structure of the Invention) Means for Solving the Problems In order to solve the above-mentioned problems, the inventors have conducted various studies and found that when fosmidomycin or its salts are freeze-dried, fosmidomycin or its salts are They discovered that a good freeze-dried powder could be obtained by adding an alkali metal halide, and as a result of further intensive research, they completed this invention. Examples of the alkali metal halides used here include sodium chloride, potassium chloride,
Examples include, but are not limited to, potassium bromobromide. The amount of alkali metal halide added to fosmidomycin or its salt is usually preferably 1 part by weight or more per 1 part by weight of fosmidomycin or its salt. In order to obtain the freeze-dried powder of the present invention, first, a mixed aqueous solution of fosmidomycin or its salts and an alkali metal halide may be prepared, and this may be freeze-dried by a conventional method. That is, the desired lyophilized powder can be obtained by freezing the above aqueous solution using ampoule or vial lyophilization, tray lyophilization, spray lyophilization, etc., and dehydrating it by sublimating the water under high vacuum. Next, the present invention will be explained using examples. Example 1 Fosmidomycin monosodium salt 300 μg
and 9 mg of sodium chloride are dissolved in 0.25 ml of distilled water for injection and filled into a 1 ml ampoule. After the filled product is cooled to -40°C and frozen, water is sublimed under high vacuum to obtain an ampoule of lyophilized powder (intradermal preparation). Example 2 Fosmidomycin monosodium salt 300 μg
and 300 μg of sodium chloride and 0.25 ml of distilled water for injection.
Dissolve in and fill into 1 ml ampoules. After the filled product is cooled to -40°C and frozen, water is sublimed under high vacuum to obtain an ampoule of lyophilized powder (intradermal preparation). (Effects of the Invention) This invention provides a freeze-dried powder of fosmidomycin or its salts for the first time, and furthermore, the freeze-dried powder thus obtained has significantly superior stability. It also has the following characteristics. This fact will be explained more specifically in the following reference examples and comparative examples. The mannitol used in the comparative examples is widely used as an excipient (stabilizer) when producing freeze-dried preparations. Reference example Fosmidomycin monosodium salt 300μg
was dissolved in 0.25 ml of distilled water for injection, filled into a 1 ml ampoule, and freeze-dried in the same manner as in Example 1.
No freeze-dried powder was obtained. Also, fosmidomycin monosodium salt 10
Attempts were made to produce freeze-dried powders using % aqueous solutions and 20% aqueous solutions, but the cake matrix collapsed (foaming phenomenon) during the drying process, and freeze-dried powders could not be produced. Comparative Example In Example, an ampoule of lyophilized powder (intradermal preparation) was produced in the same manner as in Example 1, using 50 mg of mannitol instead of 9 mg of sodium chloride. The stability of this powder and the powder obtained in Example 1 was tested by keeping it at 50°C for one month. The results are shown in the table below.

[Table] As is clear from the above table, the freeze-dried powder of the present invention exhibits extremely superior stability compared to the control.

Claims (1)

[Scope of Claims] 1. A freeze-dried powder of fosmidomycin or its salts containing fosmidomycin or its salts and an alkali metal halide. 2. The lyophilized powder of fosmidomycin or its salts according to claim 1, wherein the alkali metal halide is sodium chloride. 3. The lyophilized powder of fosmidomycin or a salt thereof according to claim 2, wherein the salt of fosmidomycin is a sodium salt. 4. A method for producing a freeze-dried powder of fosmidomycin or its salts, which comprises adding an alkali metal halide to fosmidomycin or its salts when freeze-drying the fosmidomycin or its salts.