Biotest Pharma Gmbh

Detlef Piechaczek

Dieter Rudnick

Wolfgang Moller

Norbert Kothe

Wolfgang Stephan

Ronald Kotitschke

Hans Schleussner

Herbert Dichtelmuller

Wolfgang Moeller

Michael Kloft

Detlef Rohm

Herwald Klein

Hebert Dichtelmuller

Intravenously administered chemically unmodified immunoglobulin preparation containing more than 5% of its total immunoglobulin by weight consisting of IgM and/or more than 10% of its total immunoglobulin of IgA and with a low anticomplementary activity, and method of preparing it by anion-exchange chromatography.

Unmodified intravenously administered immunoglobulin preparations

An intravenously administrable polyclonal immunoglobulin preparation for the treatment and prophylaxis of bacterial infections containing at least 50% by weight of IgM in terms of the total content of immunoglobulin, exhibiting a low anticomplementary activity, being stable in aqueous solution, and being free of viruses. It can also consist of or also contain a mixture of several monoclonal IgM antibodies. The source material for its manufacture is an immunoglobulin-containing fraction of human, animal, or bacterial provenance. The fraction is treated with an anion exchanger that is eluted with a saline or pH gradient and the eluate is optionally subjected to gel filtration, treated before or after the chromatography with .beta.-propiolactone and PEG 4000, and optionally heated. Treatment with .beta.-propiolactone and ultraviolet light, treatment with solvents and detergents, or pasteurization can also be conducted. Proteins, sugars, or mixtures of amino acids are optionally added to the preparation.

Intravenously administerable polyclonal immunoglobulin preparation

Method of manufacturing an intravenously tolerable immunoglobulin-G preparation that is free of aggregates, vasoactive substances and proteolytic enzymes and accordingly appropriate for all types of patients, especially immunosuppressed patients, from a starting material that contains immunoglobulin G but from which the coagulation factors have been removed. The starting material is treated with 0.4 to 1.5% by volume of octanoic acid and then chromatographed, especially on an ion or cation exchanger or hydrophobic matrix.

Manufacturing intravenous tolerable immunoglobulin-G preparation

Process for the preparation of an immunoglobulin solution suitable for intravenous administration from a human blood protein fraction containing immunoglobulins IgG, IgA and IgM in partially concentrated from, with the process steps: addition of acetate buffer to the protein fraction, where appropriate removal of insoluble constituents by filtration, treatment with calcium phosphate and octanoic acid, centrifugation, removal of the supernatant and treatment thereof with an adsorbent, removal of the adsorbent and sterilization by filtration.

Process for the preparation of a pharmaceutical which contains IgG, IgA

A method of producing a virus-safe, storage-stable, and intravenously tolerable immunoglobulin-G preparation. The object is to make the method appropriate for industrial-scale production and economical by means of the enrichment and multistage purification of a plasma that has had the coagulation factors removed from it or of a plasma fraction or serum fraction that contains immunoglobulin G accompanied by treatment with ion exchangers and by ultrafiltration. The precipitant is eliminated, by means of diafiltration or gelfiltration, either from the plasma that has had the coagulation factors removed from it or from the plasma fraction that contains the immunoglobulin G, and the desired ion composition is established. The resulting protein solution is subjected to fractionation over an ion exchanger to separate the immunoglobulin G. The proteolytic enzymes in the resulting immunoglobulin-G solution are removed by means of affinity chromatography over a dye linked sorbent and/or are ihibited by the addition of antithrombin III. The accordingly stabilized immunoglobulin-G solution is treated, at a protein concentration of 20 to 60 g/l and a pH 6.0 to 8.0, with 0.03 to 0.07% of .beta.-propiolactone, diluted to a protein concentration of 5 to 20 g/l and subjected to ultraviolet radiation. The accordingly sterilized dilute immunoglobulin-G solution is again diafiltered or gelfiltered to remove lower molecular-weight substances. The accordingly stabilized and sterilized solution is adjusted to the desired protein content of 2 to 16% and filtered sterile.

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Munster, Germany

Detlef Piechaczek