CS226451B1

CS226451B1 - Method of preparing gamma-globulin solutions with defined histamine contents

Info

Publication number: CS226451B1
Application number: CS739082A
Authority: CS
Inventors: Jozef Ing Csc Bulik; Stanislav Fekete; Milan Ing Pozemka
Original assignee: Bulik Jozef; Stanislav Fekete; Milan Ing Pozemka
Priority date: 1982-10-19
Filing date: 1982-10-19
Publication date: 1984-03-19

Description

The present invention relates to a process for the preparation of a histamine-defined gamaglobulin (contiguous histaglobulin) in which, after dissolution, the finished product is improved by reducing the sodium chloride concentration during freeze-drying of the injectable solution.

Recently prepared Histaglobulin is a lyophilized gamma globulin fraction of human plasma with histamine admixture. The product is made up of a 16% solution of Human Gamaglobulin Injection and is intended to combat discomfort before starting your own Specific Allergic Treatment or as a long-term therapy in cases where it fails! to identify the cause of the disease such as: bronchial asthma, migraine, allergic rhinitis, urticaria and others. (ČAP J. Refrate at the VIIIth National Congress of the General Section of JEP Ružomberok / 1961), JAROŠ F .: Pharmaco-therapeutic reports, 3/1975 /, HODEK B .: Asthma, bronchile, Avicenum (1975)).

Histaglobulin carved in Czechoslovakia after lyophilization and careful dissolution in appearance is inhomogeneous and very often appears opalescence. This suggests that the gamma globulin contained in the product during the process of the process varies somewhat.

For this reason, foreign producers of gamaglobulin for the preparation of Histaglobulin are stabilized with sodium thiosulphate. Settlement after primeneniju suehoho Histaglobulin, Ministry of Health of the USSR, Settlement for Use Chistafelobulin, Medical Academy BÍR; Instructions de utilizare Histaminoglobulina, Ministry of Health (HIR).

In Czechoslovakia, human albumin was used to stabilize the gamaglobulin used for the preparation of Histaglobulin (Czechoslovak AO No. 221 172 Stabilization of Human Gamaglobulin Solution with Low Protein Concentrations).

At the present time, the technology for the preparation of Histaglobullin consists in turning the 16% gamaglobullin solution from 0.45-0.50% sodium chloride solution to 3% protein and adjusting the pH to 5.75-5 with 5% citric acid, 80th Then 2% bentonite was added to the gamma globulin solution with stirring, and the mixture was allowed to stand for 1 hour. The gel formed is centrifuged and the supernatant is filtered through a sieve pad. The pH is adjusted to 6.8 to 6.9, followed by filtration through sterilizing pads and the gamma globulin obtained is diluted with isotonic sodium chloride solution to a 0.5 to 0.7% bleach solution. The gamma globulin solution thus prepared is mixed with a sterile isotonic saline solution containing histamine so that the final histamine concentration is 0.05-0.10 µg / ml. After complete homogenization, the formulation is filled, frozen and lyophilized.

The essence of the novel process for the preparation of Histaglobullin is that the 14.5-17.5% solution of Human Gamaglobullin is diluted with pyrogen-free water to 0.2-5.5% by weight of protein, the pH of the gamaglobullin solution is adjusted to a pH of 6.4 to 17.5%. 7.4 and add an atherile solution of histamine so that the final histamine concentration in the product is 0.05-0.10 µg / ml. The solution obtained is frozen and then lyophilized at a concentration of 0.01 to 0.05% by weight of sodium chloride. The lyophilized product is dissolved in a 0.7 to 0.9% sodium chloride solution prior to the epcolate.

The advantage of the above method of preparation of Histaglobullin over the prior art is that it substantially improves the appearance of the product after dissolution, its homogeneity and the yield.

Below are two examples of the preparation of Histaglobulln in a new way:

For 1,00 ml of a 16 ° h solution of Human Gamaglobullin Injection Solution, dilute to 0.53% protein by adding 2,900 ml pyrogen-free water. The pH of the diluted gamma globulin solution is adjusted to 6.9 and mixed with a sterile solution of histamine so that the final histamine concentration in the product is 0.08 µg / ml. The Histaglobullin solution thus prepared is dispensed into 2 ml penicillin flasks, frozen and lyophilized. the lyophilized product is dissolved in 2 ml of 0.85% sodium chloride solution.

Example 2

100 ml of a 15% injectable solution of Human gamma globulin and diluted with 2,900 ml of pyrogen-free water to 0.50% protein. The pH of the diluted gamma globulin solution is adjusted to 6.8 and mixed with sterile histamine solution so that the final histamine concentration in the product is 0.09 µg / ml. The Histaglobullin solution thus prepared is dispensed into 2 ml penicillin bottles, frozen and lyophilized. The lyophilized product is dissolved in 2 ml of 0.85% sodium chloride solution.

Appearance rating:

Table 8.1 shows the relative turbidity values in% transmittance versus distilled water measured with a Pulfrich photometer (fliter S. 3, sensitivity 2) and the scattering of the relative turbidity values of the product prepared by the building and proposed thermologist.

Table no. 1

Second Product Average relative turbidity values in% Value scatter

Claims

OBJECT OF THE INVENTION

Process for preparing a gamma globulin solution having a defined histamine content, characterized in that a 14.5 to 17.5% solution of ruddy gamaglobulin is diluted with pyrogen-free water to 0.2 to 5.5% by weight of proteins, the pH of the gamaglobulin solution is adjusted to 6.4 to 7.4, a sterile histamine solution is added such that the final histamine concentration in the product is 0.05-0.10 µg / ml, and the obtained injection solution is frozen, then lyophilized at a sodium chloride concentration of 0.01-0.05% by weight. .