A kind of production technology of intravenous immunoglobulin

Abstract

The invention provides a production process for intravenous immunoglobulin, which comprises separating the components I+II+III / II+III from healthy human plasma; Through the following chromatography: anion chromatography A, anion chromatography B, affinity chromatography C; after chromatography, the washing solution is prepared by ultrafiltration, concentration or dilution, and then filtered through a nano-membrane, incubated at a low pH value, and incubated After release, the solution is mixed, prepared and sterilized to obtain immunoglobulin for intravenous injection. The production process provided by the present invention can obtain IgG products with high yield and purity, and more importantly, the anti-A, anti-B indexes and ACA indexes of the obtained products are all greatly reduced, which meets the requirements of "Chinese Pharmacopoeia" well , and the osmolarity of the sample also meets the requirements very well.

Description

technical field [0001] The invention relates to the field of biopharmaceuticals, in particular to a production process of intravenous immunoglobulin. Background technique [0002] Immunoglobulin (Ig) is an important part of the human immune system. It is a kind of animal protein with antibody activity. It plays an important role in the recognition of bacteria and viruses and the activation of complement in the human body. Immunoglobulins in human plasma can be divided into five classes: IgG, IgA, IgM, IgD, and IgE, of which IgG is the main one. The most notable feature of IgG is that it can specifically recognize antigens and combine with them to form complexes. After the complexes are phagocytized by phagocytes, the antigens lose their toxicity and pathogenicity. Since Cohn developed the ethanol precipitation method, immunoglobulin-enriched human plasma has been widely studied and used for the treatment of various infections or congenital defects. [0003] At present, imm...

AI Technical Summary

Problems solved by technology

Chinese patent CN 103554253B discloses a preparation method for intravenous injection of human immunoglobulin, which separates II + III precipitates through two-step pressure filtration, removes component III precipitates by low-temperature ethanol pressure filtration, and then obtains the product through two-step chromatography The biological activity, yield and purity are high, the product yield is not less than 6.5g per liter of plasma, and the product purity reaches more than 99%. However, this patent does not detect anti-A and anti-B. Anti-B gel, so the content of anti-A and anti-B antibodies in the obtained IgG products is relatively high, which is easy to exceed the provisions of the "Chinese Pharmacopoeia"

Chinese patent CN 103394084B provides an immunoglobulin G concentrate that removes anti-A, anti-B antibodies and polyreactive immunoglobulin IgG, and preferably removes anti-A and anti-B antibodies. In the obtained IgG concentrate Contains no more than 23ng / mg of anti-A antibody, especially between 19 and 23ng / mg; contains no more than 20ng / mg of anti-B antibody, especially between 12 and 20ng / mg, but it has no effect on product yield and Purity is inspected

The existing research results show that in order to obtain IgG products with higher yield and purity and to remove anti-A and anti-B antibodies well, there are higher requirements for the preparation process, and the existing processes have failed to achieve good results at the same time

[0006] In addition, the existing preparation process still has the following defects that cannot be solved: 1) When the flow-through liquid after two chromatography is filtered through the nano-membrane, the anti-A and anti-B indexes of the final product meet the requirements of "Chinese Pharmacopoeia" (2010) , the ACA content is high, and the ACA index is difficult to meet the standard after incubation; 2) after octanoic acid precipitation treatment and then two times of chromatography, it is prepared by ultrafiltration, and the osmolality is prone to natural crystallization, so that the sample cannot be measured. The pressure or osmotic pressure does not meet the standard, and it is easy to make the yield low, the washing peak tail is long, and it is difficult to clean the chromatography column

Images