CS248954B1 - A mixture of IgG, IgA, IgM and transferrin immunoglobulins for intravenous and intraperitoneal use - Google Patents

Abstract

The mixture of immunoglobulins IgG, IgA, IgM and transferrin intended for intravenous administration and intraperitoneal administration consists of a concentrated mixture of immunoglobulins IgG, IgA, IgM in an amount of 0.4 to 0.7 g of transferrin in an amount of 0.1 to 0.4 g, soluble in 100 ml of an aqueous solution of albumin with a concentration of 4.5 to 5.5% by weight, which is prepared by ethanol fractionation, subsequent lyophilization and dissolution in a solution of 0.02 mol of acetyl-d,l-tryptophan and 0.02 mol of sodium caprylate. The solution thus obtained is pasteurized at 60 °C, the pH is adjusted to a value of 6.4 to 7.4 with a 0.5M sodium hydroxide solution.

Description

The invention relates to a mixture of immunoglobulins of the IgG, IgA, IgM type intended for intravenous administration, wherein human albumin is added to the mixture of immunoglobulins in order to reduce anti-complementary activity and transferrin to increase bacteriostatic effect at a concentration such that is in human plasma.

At the present time, administration of immunoglobulins by the intravenous route encounters the problem of the nativeity of the immunoglobulin molecule and the associated anti-complementarity issue. Despite the considerable efforts made in the last period, there is no formulation available at the time to allow, in concentrated form, the intravenous administration of IgA and IgM ia immunoglobulins containing transferrin to enhance the bacteriostatic effect of the administered immunoglobulin preparation and transferrin. In particular, the administration of said preparation is particularly in emergency situations in severe bacterial infections, mainly caused by Gram-negative bacteria, in cases where antibiotic and chomotherapeutic therapy often fails.

The proposed formulation of a mixture of immunoglobulins and transferrin solves this problem by providing the desired therapeutic effect by similar composition of the individual components as in human plasma.

The works of foreign authors show that the only preparation containing a higher concentration of immunoglobulins of the IgM type is a canned serum protein with a concentration of 5% - Duswald Κ. H., Miiller K., Seifert J., Ring J., Munch. Med. Wschr. 122, 22, 832-836, 1980.

The prominent bacteriostatic effect of transferrin and its place in defending against gram-negative bacteria is described by Bauer et al. 1980, Gofferje and Maintz, 1980 and Kult et al. 1975 [Bauer HW, Mellin Η. E., Grabs

GH: Infusion Therapy 6, 301-304, (6), 1980, Gofferje H., Maintz E .: Infusion Therapy 5, 268-272, 1978, Kult J., Treutlain E., Dragoun GP, Heiland: Infusion Therapy 2, 313- 318, 1975].

Technological management of reduction of anticomplementary activity in protein solutions of macromolecular nature is very difficult and not always successfully solved. The methods used so far in this field have been directed to gel filtration using different carriers, or flow dialysis, but the high cost of imported materials, labor intensity and energy intensity of flow dialysis led us to another solution.

The mixture of immunoglobulins IgG, IgA, IgM and transferrin for intravenous and intraperitoneal administration consists according to the invention of a concentrated mixture of immunoglobulins IgG, IgA, IgM in an amount of 0.4 to 0.7 grams and transferrin in an amount of 0.1 to 0.4 grams in 100 ml of a 4.5 to 5.5% by weight aqueous solution of human albumin prepared by ethanol fractionation, followed by lyophilization and dissolution in a solution of 0.02 mol of acetyl-d, 1-tryptophan and 0.02 mol of sodium caprylate. The solution thus obtained is pasteurized at 60 ° C for 10 hours, adjusted to pH 6.4 to 7.4 with 0.5M sodium hydroxide solution.

The protein solution obtained is sterilized by filtration and filled in increments of 20, 50 and 100 ml. Execution example

0.6 g of lyophilized mixture of IgG, IgA, IgM and 0.4 g of transferrin is dissolved in 100 ml of 5% w / w aqueous 1'-human albumin, homogenized after adjusting the pH to 6.5 + 0.1. , filter through sterilizing pads and fill in 20, 50 and 100 milliliters.

Claims (2)

SUBJECT A mixture of IgG, IgA, IgM and transferrin immunoglobulins for intravenous and intraperitoneal use, characterized in that it consists of 0.4 to 0.7 g of a concentrated mixture of IgG, IgA and IgM immunoglobulins and 0.1 to 0.4 g transferrin in 100 ml of an aqueous solution of human albumin at a concentration of 4.5-5.5% by weight, the albumin solution being stabilized by the addition of 0.02 mol of acetyl-d, 1-tryptophan and 0.02 mol of sodium caprylate and pasteurized at 60 ° C . 2. The composition of claim 1 comprising 0.26-0.52 g IgG, 0.1-0.2 grams IgA, 0.025-0.05 g IgM, 0.1-0. 4 g transferrin and 0.45 to 0.55 g albumin per 100 ml solution.