An analog of somatostatin with hormonal and antitumor activity was synthesized. An optimum synthesis method was developed, yielding standard pharmaceutical somatostatin analog substance for preclinical and clinical studies. A quality control method was developed for inclusion in the draft manufacturer’s pharmacopeia monograph for pharmacological somatostatin analog substance.

Синтезирован аналог соматостатина, обладающий гормональной и противоопухолевой активностью. Разработан оптимальный метод синтеза, позволяющий получать стандартную фармацевтическую субстанцию аналога соматостатина для доклинических и клинических исследований. Разработаны методики контроля качества, которые будут включены в проект ФСП на фармацевтическую субстанцию аналога соматостатина.

As part of pre-clinical pharmacokinetic study of the dosage form of the hypothalamic hormone somatostatin analogue has been developed a method for 3 H-AGG by synthesis of 3 H-tetrapeptide obtained by the bombardment of molecules thermally active substances with gaseous tritium, and cysteine. Pharmacokinetic studies AGG in 15 tissues and organs of mice when administered in the dosage form of the drug showed good accessibility to all organs and tissues, including Sa755, and a high affinity to the stomach and bone marrow. Withdrawal from the study of the animal organism in the urine and feces showed that the cumulative excretion of respectively 16 % and 78 %, and mostly ends in 24h surveillance.

As part of pre-clinical pharmacokinetic study of the dosage form of the hypothalamic hormone somatostatin analogue has been developed a method for 3H-AGG by synthesis of 3H-tetrapeptide obtained by the bombardment of molecules thermally active substances with gaseous tritium, and cysteine. Pharmacokinetic studies AGG in 15 tissues and organs of mice when administered in the dosage form of the drug showed good accessibility to all organs and tissues, including Sa755, and a high affinity to the stomach and bone marrow. Withdrawal from the study of the animal organism in the urine and feces showed that the cumulative excretion of respectively 16 % and 78 %, and mostly ends in 24h surveillance.

The photodynamic activity and pharmacokinetics of a new liposomal formulation (LF) of the sensitizer Photosense have been studied in comparison to those of the standard form (SF) representing an 0.2% aqueous solution of the parent drug. An effective therapeutic doze of the LF of Photosense in mice bearing Ehrlich tumor was 1 mg/kg, which is four times as small as the effective dose of the SF. The selectivity of accumulation in the tumor tissue 24 h after administration for the LF of Photosense was 1.5 times higher than for the SF. The drug accumulation in skin (determined by the fluorescence intensity) on the 7th days of experiment for the LF of Photosense was 1.6 times lower than for the SF. The pharmacokinetics of the LF of Photosense in mice without tumors significantly differs from that of the SF.

The photodynamic activity and pharmacokinetics of a new liposomal form (LF) of the sensitizer Photosense based on aluminum sulfophthalocyanine salts have been studied in comparison to those of the standard form (SF) representing a 0.2% aqueous solution of the parent substance. The effective therapeutic doze of the LF of Photosense in mice bearing Ehrlich's tumor was 1 mg/kg, which is four times as small as the effective dose of the SF. The selectivity of accumulation in the tumor tissue 24 h after administration for the LF of Photosense was 1.5 times higher than for the SF. The drug accumulation in skin (determined by the fluorescence intensity) on the 7th days of experiment for the LF of Photosense was 1.6 times lower than for the SF. The pharmacokinetics of the LF of Photosense in mice without tumors significantly differs from the behavior of the SF.

A synthesized analog of myelopeptide HP-2-->M[symbol: see text]-2 (Leu-Val-Val-Tyr-Pro-Trp) caused a significant (60-80%) and prolonged inhibition of s.c. grafted tumors P388, Ca-755, B-16 and sarcoma 180 in isogenic mice but did not affect the growth of tumor B-16 in nude mice. Nor did it influence proliferative activity or viability of cultured human tumor cells. The best results were obtained with s.c. injections of 0.5-2 mg/kg HP-2-->M[symbol: see text]-2, twice or trice a day, at 96 hr intervals. No symptoms of severe poisoning were registered at doses of HP-2-->M[symbol: see text]-2 100 times the therapeutic one. A pharmacokinetic study in mice revealed prolonged circulation of HP-2-->M[symbol: see text]-2 in blood and a high affinity for the bone marrow (t 1/2 (130.1 hr and 431.6 hr, respectively). HP-2-->M[symbol: see text]-2 restored in vitro the ascites P388-suppressed cytotoxicity of murine T-lymphocytes. HP-2-->M[symbol: see text]-2 is regarded as a candidate for clinical studies of its potential of immunocorrection in cancer patients suffering T-lymphocyte immunity disturbances.

Phase-I clinical studies of teraphtal and a "teraphtal + ascorbic acid" catalytic system have been completed. The dose-limiting toxicity and maximum tolerable dose were not reached even at the end of maximal dose trials. No side-effects characteristic of antitumor cytostatic drugs were registered. The gravest side-effect ever recorded was a collapse which could not be linked to teraphtal dosage and was probably caused by hypersensitivity to the drug. The drug was recommended for phase II trials.