JPS60239414A - Method for suppressing discoloration of etoposide solution - Google Patents

Abstract

PURPOSE:To suppress the discoloration of an etoposide solution, by dispersing an insoluble reducing agent in the etoposide solution, agitating the mixture, and removing the insoluble reducing agent by filtration. CONSTITUTION:An etoposide solution (e.g. solution of etoposide in ethanol, polyalkylene glycol, etc.) is added with 0.01-10wt%, preferably 0.05-0.5% insoluble reducing agent (e.g. sodium sulfite, sodium pyrosulfite, L-ascorbic acid, thiourea, etc.), and the additive is suspended in the solution by agitating at room temperature for >=10min. The obtained suspension is filtered to remove the insoluble reducing agent and obtain the etoposide solution having suppressed discoloration. In the case of using said solution for injection, the discoloration-suppressing effect can be further improved by sealing the solution together with an inert gas (e.g. N2, He, Ne, Ar, etc.) in an air-tight container such as ampule.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Application Field] Ethopone solution is used as an anticancer injection.

[Prior art]

Conventionally, there is no known method for suppressing discoloration of etoposide solutions.

[Problems to be solved by the present invention]

Injectable solutions of etoposide may change color over time due to differences in the manufacturing method, purification method, etc. of the raw material of etoposide. The present invention suppresses discoloration over time in such cases.

[Failure to solve the problem]

The present invention relates to a method for suppressing discoloration of an etoposide solution, which comprises suspending and stirring an insoluble reducing agent in an etoposide solution, and then filtering the suspension to remove the insoluble reducing agent.

The etoposide solution to be treated in the method of the present invention is not particularly limited and includes, for example, an ethanol polyalkylene glycol solution of etoposide. In the case of this injection solution, an organic acid such as citric acid, co-I-phosphoric acid, tartaric acid, or malic acid, which can be used for pharmaceutical purposes, is added to 1 part (part by weight, the same applies hereinafter) of etoposide.

It is more preferable to contain about 0.3 to 2 parts.

The insoluble reducing agent to be used is not particularly limited as long as it is insoluble in the etoposide solution. Examples include sodium sulfite, sodium pyrosulfate, sodium bisulfate, sodium thiosulfate% L-ascorbic acid, cysteine hydrochloride, and Rongalit.

and thiourea, and these reducing agents are preferably used in powder form.

The amount of the reducing agent added cannot be determined unconditionally as it varies depending on the etoposide concentration of the etoposide solution, but it is 0.01 to 10% (the same weight and below), preferably 0.02 to 1%, relative to the etoposide solution to be normally treated. , more preferably 0.0
It is about 5 to 0.5 inches.

Processing time varies depending on processing amount, processing temperature, etc., but at room temperature 1
A time of 0 minutes or more, for example, about 10 to 60 minutes is sufficient.

When the ethopone solution treated by the method of the present invention is used as an injection solution, an inert gas such as nitrogen, helium,
If it is sealed in a sealed container such as an ampoule together with neon, argon or carbon dioxide gas, the effect of inhibiting discoloration can be further enhanced.

[Effects of the present invention]

When the treatment of the present invention is performed, the discoloration rate can be suppressed to less than half that of the case without treatment. Amp 1 with gas. Fill 5 cups, 1 cup, 4. It can prevent discoloration and □.

Example 1 Etoposide 20■, polyethylene glycol 40060
To an etoposide solution consisting of 0Wq% polynorbate 80 8011v, anhydrous citric acid 2W, benzyl alcohol 10mg, and anhydrous r-tanol 688 cape, 1g of saliva hydrogen sulfate powder was added, and after stirring at room temperature for about 30 minutes, it was filtered. The sodium hydrogen sulfate powder is separated in a furnace using a glass filter. The r solution was filtered through a sterilization filter with an opening of 0.22 μm, and then filled into ampoules to obtain an injection.

In this example, when filling the ampoule, the ampoule was filled with carbon dioxide gas, and an injection was obtained in the same manner.

Example 2 An injection can be obtained in the same manner as in Example 1 using Rongalit and sodium thiosulfate as reducing agents.

Test Examples Each etoposide injection obtained in the example was stored at 50°C for 30 days. The color of the etoposide solution immediately after production and the color of the etoposide solution after storage were observed with the naked eye, and the wavelength 4
The transmittance at 60 nm was measured, and the rate of color change was determined using the following formula. The results are shown in the table below.

Discoloration rate (%) = ((Transmittance immediately after manufacture) - (Transmittance after storage)) ÷ (Transmittance immediately after manufacture) X100 Table 1 Patent applicant Nippon Kayaku Co., Ltd.

Claims (1)

[Claims] 1. A method for suppressing discoloration of an etoposide solution, which comprises suspending and stirring an insoluble reducing agent in an etoposide solution, and then filtering to remove the insoluble reducing agent.