Csl Behring Ag

Zlb Behring Ag

Rotkreuzstiftung Zentrallaboratorium Blutspendedienst

Rotkreuzstiftung Zentrallaboratorium

Red Cross Foundation Central Laboratory Blood Transfusion Service Src

Gerhard Hodler

Reinhard Franz Bolli

Peter Lerch

Regula Styger

Martin Stucki

Vreni Fortsch

Bernard Wuest

Katharina Gennari

Rene Bruegger

The present invention relates to a protein preparation having increased stability, comprising a stabilizer selected from the group consisting of non-polar and basic amino acids and having a pH of 4.0 to 5.2. The invention further relates to a pharmaceutical composition and a method of stabilizing protein preparations.

Immunoglobulin preparations having increased stability

The present invention relates to a protein preparation having increased stability, comprising a stabiliser selected from the group consisting of non-polar and basic amino acids and having a pH of 4.0 to 5.2. The invention further relates to a pharmaceutical composition and a method of stabilising protein preparations.

Immunoglobulin preparations, particularly liquid preparations of immunogllin G for intravenous infusion, are stabilized against dimer formation by the addition of one or more amphiphilic stabilizers. Preferred amphiphilic stabilizers are nicotinic acid derivatives, particularly nicotinamide, and naturally-occurring .alpha.-amino acids having a lipophilic side chain, for example phenylalanine, proline, leucine and isoleucine.

Liquid immunoglobulin formulations

Reconstituted high density lipoproteins (rHDL) are produced from apolipoproteins and lipids in that an aqueous apolipoprotein solution with a concentration of 1-40 g protein/l is mixed with an aqueous lipid-detergent solution without mandatory addition of organic solvents, the molar ratio of lipid to detergent being 1:0.5 to 1:4 and the weight ratio of lipid to detergent being 1:1.5 to 1:5, the resultant apolipoprotein-lipid-detergent mixture then being incubated at a temperature in the range of the phase change temperature of the lipid in water .+-.10.degree. C., and the detergent being at least partially removed. The rHDL are useful for various prophylactic and therapeutic treatments of diseases that have a connection with lipids and lipidoidal substances. This method is especially suitable for technical and industrial production.

Method of producing reconstituted lipoproteins

An anti-D immunoglobulin G-preparation is produced in high-yield from human plasma containing anti-D IgG, or a plasma fraction containing an anti-D IgG, in which (A) the plasma, or the plasma fraction, with a pH in the range of pH 3.5 to 6.5 and a conductivity value in the range of 2 to 4 mS/cm, is subjected to ion exchange chromatography with an adsorbent which has carboxymethyl groups as functional groups, the anti-D IgG being bound to the adsorbent, (B) the adsorbent with the bound anti-D IgG is first rinsed with a wash solution at a pH in the range of 5 to 8 and a conductivity value in the range of 2 to 4 mS/cm, and the anti-D IgG is subsequently eluted, and further (C) the eluted anti-D IgG at a pH in the range of 6 to 8 and a conductivity value in the range of 2 to 4 mS/cm is treated with an alkaline adsorbent with ion-exchange characteristics in order to bind undesired components, and finally, the anti-D IgG is concentrated. The non-infectious anti-D concentrate thus obtained possesses a high specific activity of more than 1% anti-D IgG per gram of total IgG.

Growing community of inventors

Worb, Switzerland

Gerhard Hodler