FR2522268A1 - Stabilised live mumps vaccine - contg. as stabiliser albumin and/or gelatin, has anticancer activity - Google Patents

Abstract

COMPOSITION OF A STABILIZED URBAN VACCINE, CHARACTERIZED BY INCLUDING A LIVE URBAN VACCINE AND A STABILIZING AMOUNT OF AT LEAST ONE STABILIZER CHOSEN FROM ALBUMIN AND GELATIN. THE PROCESS FOR STABILIZING AN ANTI-URBAL VACCINE IS CHARACTERIZED BY CONTACTING AN ANTI-HURLI VACCINE WITH ALBUMIN, GELATIN OR THEIR MIXTURE AS A STABILIZER.

Description

 The present invention relates to a preparation of live mumps vaccine, and more particularly to a mumps vaccine preparation, characterized in that an amount effective to stabilize a formulation of live mumps vaccine is added. albumin and / or gelatin to the preparation of live mumps vaccine.

 The mumps vaccine is prepared by inactivating the mumps virus or reducing its toxicity.

The mumps virus is known as a virus that causes epidemic parotitis. After the discovery of this virus by Johnson et al. in 1934, its cultivation became possible on chicken egg, vitelline membrane, amniotic ca vity, etc ..., and an inactivated mumps vaccine and a live mumps vaccine (hereinafter referred to as "LMV") were been prepared from it.

There is now a low-titre, high-titre XLMV, so that the inactivated mumps vaccine has almost lost all practical interest, although the "LMV" was initially The value of "LMV" as a drug is now being used as a vaccine to control the mumps virus, and is currently of increasing interest because its anticarcinogenic action has been clinically demonstrated later in addition to its original role.

 In order to improve the stability of the preparation of "LMV" which has acquired such utility the Applicant has carried out in-depth studies on the stabilization of this product, which has hitherto been provided in the form of a liquid product, and on the stabilization of this product at the time of the lyophilization treatment, and the stabilization of a dry sample over time. These studies have led to this finding that "LMV" becomes remarkably stable in the presence of albumin, gelatin or their mixtures, not only in an aqueous medium, but also in the form of dry solids. The present invention is based on this discovery.

 In accordance with the present invention, there is thus provided an "LMV" composition comprising "LMV" and a stabilizing amount of at least one stabilizer selected from albumin and gelatin.

 The "L9J" composition of the invention may be an aqueous suspension of "LMV" or a powdery solid. It may contain adjuvants, preferably usable for administration to humans. In the preparation of a solid composition from this aqueous suspension, the decrease of the "LMV" activity can be avoided by the use of the hyophilization technique.

 As albumin for use in the invention, human albumin is preferred because of its antigenicity. However, the albumin used is not limited to human albumin, and a wide variety of commercially available albumins which can be administered to humans for medical treatment can be used without reserve. As gelatin, any gelatin may be used without reserve in so far as it is suitable for medical treatment. It is preferred that this gelatin is a uniform composition.

The "W" of the present invention is not critical, it can be between any "LMV" since its toxicity is impaired by the well-known method for the preparation of "LMV", and where it is purified to a degree permitting its use in medical treatment. In this memo, mention will be made of the "LMV" from a strain of Urabe offered by
Biseibutus Kenkyujo, Osaka Daigaku (Reserach Institute of Micro-organisms, University of Osaka).

The higher the amount of stabilizer such as albumin, gelatin, etc., the stronger the stabilizing effect, although this effect also depends on the amount of "LMV" in the preparation. When the stabilizer is added to an aqueous medium, the final concentration of stabilizer should be 1 to 10
P / V. When added to a powder, its final concentration should be 5 to 20% w / w. When albumin and gelatin are used in combination in an aqueous medium, their final individual concentration should be 0.1 to 5% w / v and their total final concentration should be 1 to 10% W / V. When used in combination in a powder, their final individual concentration should be 1 to 10% w / w and their total final concentration should be 5 to 20% w / w.

The invention will be explained below in more detail with reference to the experimental examples and examples. Pfu ("LMV" title lysis plate forming unit), used in the experimental examples, were determined according to the description of "Virrus Jikkengaku (Experimental Virology)", referred to by Gakuyukai of Kokuritsu Yobo Eisei Kenkyujo (The
National Institute of Health, Japan) and published by Xaruzen (1967).

 Experimental Example 1: Stabilizing effect on an aqueous medium containing "LMV".

 Various stabilizers are added to 6.5 x 10 5 pfu / ml (0.9% aqueous sodium chloride solution) of each of the LMV suspensions. On the mixtures thus obtained, the stability is determined by allowing them to remain in a thermostatically controlled water bath maintained at 200C. The results are given in Table 1.

TABLE 1

<tb><SEP> Concentration <SEP> Residual <SEP> Title
<tb><SEP> Final <SEP> Stabilizer <SEP> at the <SEP> end <SEP> of a
<tb><SEP> t <SEP> (P / U) <SEP> months <SEP> to <SEP> 200C <SEP> (%)
<tb><SEP> Albumin <SEP> 1 <SEP> 40
<tb><SEP> 9 <SEP> 50
<tb><SEP> Gelatin <SEP> 2 <SEP> 43
<tb><SEP> n <SEP> 8 <SEP> 59
<tb><SEP> Albumin <SEP> +
<tb><SEP> Present <SEP> Gelatin <SEP> 0.1 <SEP> + <SEP> 2 <SEP> 49
<tb> invention <SEP> n <SEP> 0.5 <SEP> + <SEP> 1 <SEP> 42
<tb><SEP>"<SEP> 1.0 <SEP> + <SEP> 1 <SEP> 46
<tb><SEP> 2.0 <SEP> + <SEP> 0.1 <SEP> 52
<tb><SEP>"<SEP> 5.0 <SEP> + <SEP> 0.1 <SEP> 62
<tb> Witness <SEP> None <SEP><1
<Tb>
Experimental 2: stabilizing effect on a lyophilized "LMV".

 Various stabilizers are mixed with a lyophilized "LMV" having a total activity of 1.8 x 105 m.p.

The mixtures are subjected to a stability test by leaving at -100C for one month. The results are given in Table 2.

TABLE 2

<tb><SEP> Concentration
<tb><SEP> Stabilizer <SEP> in <SEP> the <SEP> pro- <SEP> Title
<tb><SEP> residual <SEP> sec <SEP>% <SEP> residual
<tb><SEP> (P / P),
<tb><SEP> Albumin <SEP> .5
<tb><SEP> 84
<tb><SEP> Gelatin <SEP> 5 <SEP> 83
<tb><SEP> n <SEP> 10 <SEP> 96
<tb><SEP> Albumin <SEP> +
<tb> Present <SEP> Gelatin <SEP> 1 <SEP> + <SEP> 1 <SEP> 84
<tb> invention <SEP> n <SEP> I <SEP><SEP> + <SEP> 10 <SEP> 96
<tb><SEP> n <SEP> 1+ <SEP> 15 <SEP> 97
<tb><SEP> 10 <SEP> + <SEP> 1 <SEP> 96
<tb><SEP> 5 <SEP> + <SEP> 10 <SEP> 95
<tb><SEP> n <SEP> e + <SEP> 8 <SEP> 97
<tb> Witness <SEP> None <SEP><10<SEP>
<Tb>
Example 1
5
The "LMN" is diluted to a titer of 2 × 10 5 pfu / ml with a saline solution of sodium chloride (100 ml) to which is added 5% w / v of albumin and 0.5% w / v of gelatin . The resulting mixture is sterilized and filtered. Pour the filter by portion and lyophilize it. The freeze-dried "LMV" thus obtained has a titer of 6.9 × 10 5 pfu / mg. It retains an activity of 6.8 x 108 pfu / mg even after being stored at -100C for 1 month.

Example 2
A lyophilized "LMV" is prepared by repeating the procedure of Example 1 except that the 5% w / v albumin and the 0.5% w / v gelatin used in Example 1 are replaced by 8. % W / v albumin.

Claims (1)

 CLAIM  Composition of freeze-dried mumps vaccine, characterized in that it comprises a live mumps vaccine and 5 to 20 P / P of at least one stabilizer chosen from albumin and gelatin.