Biological Evaluation of Medical Devices in the Form of Suppositories for Rectal and Vaginal Use

Abstract

Background. Programs of preclinical safety studies of the health care products depend on the regulatory status of the investigated products. The classification of such products, in particular suppositories for rectal and vaginal use, is a critical step of developing tactics for their biological evaluation. Adaptation of biological evaluation methods for the medical devices based on the combination of biologically active substances, as well as evaluation of the results of such studies is urgent task of biomedicine. Objective. To substantiate the regulatory status and to carry out a biological evaluation of medical devices in the form of vaginal suppositories based on octenidine dihydrochloride ("Prodexyn") and in the form of rectal suppositories based on Saw palmetto, Levisticum officinale and Calendula officinalis extracts ("Pravenor"). Methods. Biological evaluation was conducted according to the requirements of ISO 10993 standards using in vitro and in vivo biological test systems (cytotoxicity in cell culture and the MTT test, sensitizing and irritating effect in guinea pigs). Results. The cytotoxicity (СС50) of the medical device "Prodexyn" extract in Vero cell culture was 8.35 μg/ml calculated as octenidine dihydrochloride and 416.65 μg/ml calculated as dexpanthenol. "Pravenor" medical device was found to be non-toxic in Vero cell culture. According to the results of MMT assay CC50 for octenidine dihydrochloride was 1.67 μg/ml, and 83.33 μg/ml – for dexpanthenol. CC50 indicators calculated for the different active ingredients of the medical device "Pravenor" were the following: 50 mg/ml for the dwarf palm berries extract (Saw palmetto), 16.67 mg/ml for the lovage roots extract (Levisticum officinale), and 16.67 mg/ml for the calendula flowers extract (Calendula officinalis). No sensitizing or skin irritating effects were observed in guinea pigs. Conclusions. Biological evaluation of medical devices in the form of rectal suppositories "Pravenor" and vaginal suppositories "Prodexyn" performed using in vitro and in vivo biological systems. It was demonstrated an acceptable level of safety of the products. The MTT test was 5 times more sensitive than the Vero cell culture method in determination of cytotoxicity.