Stakhorska M. Pharmacological study of the combined cream for the treatment of proctologic diseases

In the thesis theoretical and experimental basis for the composition of the cream for the treatment of proctologic pathology, as well as the results of an experimental study of its therapeutic efficiency and the main indicators of safety profile are presented. Four samples of the rectal combined cream (RCC) which are offered for the treatment of proctologic pathology including anal fissures (AF) were studied. All samples were developed by a team of researchers under the guidance of the doctor of pharmaceutical sciences, professor N. O. Lyapunov. In screening research the most pronounced therapeutic effect among the studied samples of the RCC was found in a sample №4 (RCC-4). It was found that this sample significantly restricted the development of inflammation, purulent and necrotic complications. It also stimulated reparative processes, which was manifested by the reduction of all major symptoms of the pathological process and the acceleration of the complete healing of AF. Among animals treated with the RCC-4, complete epithelization of the defect of the mucous membrane of the anal canal was first observed at 7th day of the experiment, while the first case of epithelization in animals treated with drug comparison “Proctozan” was registered at 10th day. Thus, the indicated investigated sample showed a significant advantage over the drug comparison "Proctozan" in terms of expressive therapeutic effect. On the model of chronic anal fissure (ChAT), it was shown that the use of RСС-4 contributed to a decrease in the severity of inflammation (a 31% decrease in blood leukocyte shift index (p <0.05) compared with animals of the control pathology group), purulent-necrotic complications, and mortality among experimental animals and a decrease in the phenomena of endogenous intoxication at the peak of pathology (35% reduction in Krebs index (p <0.05) compared with animals of the control pathology group). It was morphologically established that under the influence of RCC-4, signs of hypertonicity of the internal anal sphincter were not detected at all, or were slightly expressed in some animals. Comparison drug ointment "Proctosan" was inferior in effectiveness to RCC-4, which to a greater extent limits the development of key mechanisms of chronicity of AT and promotes its healing. The study of anesthetic/analgesic action of RCC-4 on models of spontaneous and induced pain response in rats showed that the investigated drug has a pronounced fast-acting anesthetic effect (latent period of 3 to 5 minutes) and lasts more than five hours. The strength, duration and rate of development of the local anesthetic effect of the RCC-4 is not different from the reference drug – a monocomponent rectal ointment with lidocaine. Thus, the obtained results allow us to conclude that the administration of diltiazem and methyluracil in the study cream did not reduce the manifestations of local anesthetic activity of lidocaine. Safety profile data for RCC-4, including acute toxicity studies in mice, rats and rabbits; subchronic toxicity in rabbits and rats; locally irritating and sensitizing effect on guinea pigs, indicate the absence of toxic and irritant properties. The obtained data allow us to offer the RCC-4 as a potential drug for the treatment of anal fissures and can be used as an experimental justification for the effectiveness of the study drug in proctology.