Ashraf A Q, Liau M C, Mohabbat M O, Burzynski S R
Drugs Exp Clin Res. 1986;12 Suppl 1:37-45.
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.
抗瘤氨酸A10（3-苯乙酰氨基-2,6-哌啶二酮）在水中的溶解度较差。为了使其在制备抗瘤氨酸A10注射液时更易溶解，该化合物必须转化为其钠盐。研究发现，在中和过程中，A10会发生碱性水解，生成两种成分，即IIa和IIb。然而，研究发现A10在室温下对酸性水解具有相当的抗性。在较高温度（110摄氏度）下，反应很容易进行，60分钟后该化合物完全水解。在多次实验中，碱性水解产物的比例为4:1，保持非常恒定。随后它们被鉴定为苯乙酰谷氨酰胺和苯乙酰异谷氨酰胺。在模拟胰液中对A10进行部分水解时，也发现了这两种化合物的类似比例，这表明A10的至少一些抗癌作用可能归因于这两种降解产物的作用。因此，决定制备一种抗瘤氨酸A10注射液制剂，其浓度为100mg/ml，是苯乙酰谷氨酰胺和苯乙酰异谷氨酰胺钠盐的4:1混合物。在一组160只HA/1CR瑞士小白鼠中进行的慢性毒性研究中，该制剂在测试一年时未显示出任何显著的毒性作用。
