Protein stabilisation using additives based on multiple electrostatic interactions.
A method of elevating the storage lifetime of purified proteins has been discovered which appears to confer stability to all proteins investigated and may therefore be classed as generic in action. The basic methodology involves the formation of multiple electrostatic complexes between the protein and selected soluble polyelectrolytes to give protein-polyelectrolyte (PP) complexes and then to add solutions of polyalcohols or other compounds containing multiple hydroxyl groups. Dehydration of the resulting solution by vacuum evaporation, freeze drying or forced air convection produces a dry film or powder of stabilised protein. The method has been used mainly in the preparation of active enzymes for analytical tests. It has also been found that the formation of PP complexes also enhances the stability of enzymes in solution and the technique may be applicable to the stabilisation of virus suspensions by polycations. Examples of stabilised enzymes prepared by these methods are given and the proposed mechanism of stabilisation and applicability of the method to shelf-stable vaccine products are discussed.
Gibson
T D
TD
Department of Biochemistry and Molecular Biology, University of Leeds, UK.
D000179:Acrylates / Q000494:pharmacology*; D000429:Alcohol Oxidoreductases / Q000737:chemistry / Q000187:drug effects; D003637:DEAE-Dextran / Q000494:pharmacology; D004355:Drug Stability; D004587:Electrophoresis, Agar Gel; D004798:Enzymes / Q000737:chemistry / Q000187:drug effects*; D005949:Glucose Oxidase / Q000737:chemistry / Q000187:drug effects; D006735:Horseradish Peroxidase / Q000737:chemistry / Q000187:drug effects; D006358:Hot Temperature; D011205:Povidone / Q000494:pharmacology*; D011310:Preservatives, Pharmaceutical / Q000494:pharmacology*; D011485:Protein Binding; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology*; D055672:Static Electricity
D000179:Acrylates; D004798:Enzymes; D011310:Preservatives, Pharmaceutical; D000644:Quaternary Ammonium Compounds; C103642:Gafquat HS 100; C103643:Gafquat 755N; D003637:DEAE-Dextran; D000429:Alcohol Oxidoreductases; C019643:alcohol oxidase; D005949:Glucose Oxidase; D006735:Horseradish Peroxidase; D011205:Povidone