Клиническое исследование эффективности и безопасности препарата Визомитин®, глазные капли, у пациентов с возрастной катарактой

PURPOSE: The assessment of possibility to add a new indication for the registered pharmaceutical. Evaluation of safety and efficacy of Visomitin® compared to placebo in patients with age-related cataracts. METHODS: A randomized, double-blind, placebo-controlled clinical study of Visomitin® eye drops in patients with age-related cataracts was conducted in accordance with Good Clinical Practice guidance, the Declaration of Helsinki and the Russian regulatory requirements. The study included 80 patients (23 men and 57 women) aged 45 to 75 years with diagnosed age-related cataract. All subjects were randomized into two groups of 40 patients each. In the treatment group patients received Visomitin® eye drops and in the control group, patients were given placebo (vehicle, i.e. eye drops with the same composition as Visomitin® except for the active substance SkQ1) in the form of instillations of one drop per each eye three times daily for six months. The study comprised 7 monthly visits. The following standard ophthalmological examinations were used to evaluate the effectiveness of the therapy: visual acuity measurement, refractometry, biomicroscopy of the eye, ophthalmoscopy, tonometry, computer perimetry, densitometry. At certain visits lacrimal fluid was taken for evaluation of its antioxidant activity. Blood pressure and heart rate were measured as a part of safety evaluation which also included documentation of complaints and adverse events. Concomitant therapies were also documented. RESULTS: Analysis of safety parameters showed Visomitin® to be safe and well tolerated for patients with age-related cataract. Practically no adverse effects were documented during the study. In both groups a decrease of the number of patients with subjective complaints was observed. These complaints included: visual deterioration, dryness, grittiness, burning eyes, eye fatigue. The decrease of the number of complaints in the Visomitin® group was more pronounced than in the placebo group. During the first months of treatment an improvement of visual acuity was observed in both groups. This result can be explained by a protective effect of hypromellose contained in both Visomitin® and placebo. However, between the 4th and the 6th months, the improvement in visual acuity significantly slowed down in the placebo group, while positive dynamics remained the same in the Visomitin® group. At the end of the treatment visual acuity increased by more than 50% in Visomitin® group and remained at the level of 10-15% in the placebo group (statistically significant difference between placebo and Visomitin® groups,

Synthesis, Characterization, and Preclinical Evaluation of a Small-Molecule Prostate-Specific Membrane Antigen-Targeted Monomethyl Auristatin e Conjugate

Prostate cancer is the second most common type of cancer among men. Its main method of treatment is chemotherapy, which has a wide range of side effects. One of the solutions to this challenge is targeted delivery to prostate cancer cells. Here we synthesized a novel small-molecule PSMA-targeted conjugate based on the monomethyl auristatin E. Its structure and conformational properties were investigated by NMR spectroscopy. Cytotoxicity, intracellular reactive oxygen species induction, and stability under liver microsomes and P450-cytochrome species were investigated for this conjugate. The conjugate demonstrated 77-85% tumor growth inhibition levels on 22Rv1 (PSMA (+)) xenografts, compared with a 37% inhibition level on PC-3 (PSMA (-)) xenografts, in a single dose of 0.3 mg/kg and a sufficiently high therapeutic index of 21. Acute, chronic, and subchronic toxicities and pharmacokinetics have shown that the synthesized conjugate is a promising potential agent for the chemotherapy of prostate cancer. © 2021 American Chemical Society