JPS59181223A - Stabilization method for interferon - Google Patents

Abstract

PURPOSE:Interferon is stabilized by adding glucose to inteferon aqueous solutions. CONSTITUTION:Interferon is stabilized by adding glucose to an interferon aqueous solution, or mixing an interferon aqueous solution with a glucose aqueous solution or dissolving freeze-dried interferon in a glucose aqueous solution such as a glucose injection solution. Further, in addition to the glucose, isotonicity, pH-controller, soothing agent, antiseptic and other additives may be added. Thimerosal is an excellent antiseptic for interferon aqueous preparations. The combination of glucose and thimerosal gives antiseptic and stabilized interferon preparations.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for stabilizing interferon. More specifically, it is a method for stabilizing interferon characterized by adding glucose to an aqueous interferon solution.

Interferon is a type of glycoprotein produced by animal cells, including humans, when stimulated by viruses or other substances, and is a very useful substance that has viral growth-inhibiting and antitumor effects.

There are various types of interferon, which are broadly classified into α, β, and γ, and each type is expected to have slightly different effects in terms of medicinal efficacy, etc.

However, all types of interferon have poor stability in a solution state, making it difficult to make them into aqueous injections, and even in the case of freeze-dried injections, there are concerns about stability after redissolution. In addition, especially when administering drugs over a long period of time, such as by intravenous drip injection, a drop in titer during that period is unavoidable, which is a big problem.

Therefore, in order to improve the stability in the solution state, studies are underway using various liquids commonly used for injections, but satisfactory results have not yet been obtained.

The present inventors have also continued research regarding the above points for many years. As a result, it was completely unexpectedly discovered that the addition of glucose to an aqueous interferon solution specifically and significantly stabilizes its activity.

That is, the present invention was completed based on the successful stabilization of interferon activity through coexistence with glucose.

The medical merits obtained by the present invention are extremely large, and the present invention is considered to be very significant in the sense that it has made it possible to supply a safe and reliable interferon preparation.

Note that the concentration of glucose is not particularly limited, but it is preferably added so that the final concentration is 0.5 to 10 W/V%.

Further, as a method for adding glucose, glucose may be added to an aqueous interferon solution, an aqueous interferon solution and an aqueous glucose solution, such as a glucose injection solution, may be mixed, or a lyophilized product of interferon may be added to an aqueous solution of glucose, such as a glucose injection solution. It may be dissolved in an injection solution.

The present inventors have separately discovered that a stable lyophilized interferon preparation can be obtained by adding amino acids or amino acids and human serum albumin to an interferon aqueous solution and lyophilizing the mixture. can be used as the above-mentioned lyophilized product of interferon.

Furthermore, in addition to glucose, an isotonic agent, a pH adjuster, a soothing agent, a preservative, etc. may be added to the interferon aqueous solution.

Furthermore, the present inventors have discovered that thimerosal is an excellent preservative for aqueous interferon preparations, and by using it in combination with the method of the present invention, it is possible to obtain interferon preparations that are stable and have a preservative effect. I can do it.

The invention will be explained more clearly in the following experimental examples.

Example interferon solution (8.16 x 106 in 0.5 companies)
(including interferon alpha in international units) 0.5 mA,
Glucose injection (concentration of glucose is 5 W/V%)
The stability of a mixture of 250ml, 250mt of physiological saline, or 250rrLt of comprehensive amino acid injection solution was compared.

The titer of interferon was measured by a dye uptake method using a microassay method according to the National Institutes of Health.

The results are shown in Table 1, and while the titer decreased significantly when mixed with physiological saline and comprehensive amino acid injection, there was almost no decrease in titer when mixed with glucose injection. , a stabilizing effect on interferon α was observed.

Table 1 (Note) The titer is expressed as a relative content percentage when the titer at time 0 is taken as 100.

Next, examples of the present invention will be shown, but these examples are not intended to limit the invention.

Example 1 Interferon solution (8,16 x 1 in 0,5 ynt)
Contains 0613iI units of interferon alpha) 0
．． Add 5 ml of glucose injection solution (the concentration of glucose is 5
W/V%) to 250 ml to obtain a stable infusion solution.

Example 2 Interferon solution (8.16 x 1 in 0.5 rnt)
0.5 mt (contains 06 international units of interferon alpha)
Glucose injection solution (glucose concentration is 5W/V%) 25
0 tnL to obtain a stable interferon α solution.

Example 8 Interferon solution 8.16 x 1 in 10.5 ynt
0.5rn (contains 06 international units of interferon alpha)
A stable interferon α solution was obtained by adding glucose to the solution at a final concentration of 5 W/V%.

Claims (1)

[Claims] A method for stabilizing interferon characterized by adding glucose to an aqueous interferon solution.