Preclinical studies on antineoplaston A10 injections.
Antineoplaston A10 (3-phenylacetylamino-2, 6-piperidinedione) has poor solubility in water. In order to make it more soluble for the preparation of Antineoplaston A10 injections, the compound has to be converted into its sodium salt. It was found that during neutralization A10 undergoes basic hydrolysis with formation of two components, IIa and IIb. However, A10 was found to be fairly resistant to acid hydrolysis at room temperature. At a higher temperature (110 degrees C) the reaction proceeded easily and after 60 min the compound was completely hydrolysed. The ratio of 4:1 of products of basic hydrolysis remained very constant in a number of experiments. They were subsequently identified as phenylacetylglutamine and phenylacetylisoglutamine. A similar ratio of these two compounds was found during partial hydrolysis of A10 in simulated pancreatic juice, indicating a possibility that at least some of the anticancer effects of A10 are attributable to the action of these two degradation products. A decision was therefore made to produce a formulation of Antineoplaston A10 injections, 100 mg/ml as a 4 : 1 mixture of sodium salts of phenylacetylglutamine and phenylacetylisoglutamine. This formulation did not show any significant toxic effects when tested for one year in chronic toxicity studies in a group of 160 HA/1CR Swiss white mice.
D000818:Animals; D004353:Drug Evaluation, Preclinical; D004355:Drug Stability; D005973:Glutamine / Q000031:analogs & derivatives / Q000138:chemical synthesis; D006868:Hydrolysis; D007267:Injections; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010455:Peptides / Q000032:analysis / Q000138:chemical synthesis / Q000633:toxicity*
D010455:Peptides; D005973:Glutamine; C003089:phenylacetylglutamine