title: The influence of pH on heat denaturation of anti-haemophilic cryoprecipitate.
abstract: The influence of pH on heat denaturation of anti-haemophilic cryoprecipitate (CP) was studied by using phosphate and citrate buffers at three different pH levels for processing lyophilized, heat treated CP. The solubility and the content of FVIII:C and fibrinogen were determined following heating at 68 degrees C for 24 hours and compared to "ordinary", non-heated CP. Both the solubility and the biological activity were best preserved in the most acidic samples (pH 5.7-6.7), these batches equalled non-heated CP. At higher pH, heat treatment resulted in reduced solubility and a more pronounced loss of FVIII:C and fibrinogen. Amino acids (Syntamin 17) have previously been shown to stabilize CP during heat treatment. Some of the stabilizing effect seems to be due to a large buffering capacity, maintaining a low pH during lyophilization and heating. Raising the pH level in Syntamin-CP from 6.6 to 7.8 resulted in decreased solubility and FVIII:C content. The quality of heat treated, acidic Syntamin-CP was comparable to that of heated, acidic phosphate- and citrate-CP. We conclude that buffers used for processing heat treated CP should be of low pH, and that acidic buffers may replace Syntamin without lowering the quality of the heated product.
mesh_terms: D000596:Amino Acids / Q000494:pharmacology; D001793:Blood Preservation / Q000379:methods*; D002021:Buffers; D002951:Citrates / Q000494:pharmacology; D004573:Electrolytes; D005169:Factor VIII / Q000032:analysis* / Q000627:therapeutic use; D005612:Freeze Drying; D005615:Freezing; D005947:Glucose; D006358:Hot Temperature; D006801:Humans; D006863:Hydrogen-Ion Concentration; D057947:Parenteral Nutrition Solutions; D010710:Phosphates / Q000494:pharmacology; D011489:Protein Denaturation / Q000187:drug effects; D012995:Solubility; D012996:Solutions
chemical_list: D000596:Amino Acids; D002021:Buffers; D002951:Citrates; D004573:Electrolytes; D057947:Parenteral Nutrition Solutions; D010710:Phosphates; D012996:Solutions; C545824:amino-acid, glucose, and electrolyte solution; D005169:Factor VIII; D005947:Glucose