Experimental Approval of the Efficacy of the Combined Composition Rectal Cream New Test-samples in the Conditions of Acute Complicated Anal Fissure in Rats

Anal fissure (AF) is one of the most common anorectal problems. The severity of the disease, the chronicity of the pathological process and frequent complications lead to a sharp deterioration in the quality of life of patients. An important place in the treatment of anal fissure is occupied by drugs that affect its key mechanism of pathogenesis, namely, reduce the muscle tone of the internal anal sphincter and have anti-inflammatory, analgesic, and reparative properties.Aim: conducting of screening studies of the effectiveness of new test samples of rectal cream of the combined composition (RCCC) on the model of acute complicated anal fissure in rats and determining the optimal composition of the potential drug.Materials and methods. The research was conducted on the basis of the Central Scientific Research Laboratory of the National Pharmaceutical University (CSRL NUPH) in the spring (April) season of 2015 on the female rats.A study of test specimens of the rectal cream of the combined composition was performed on a modified model of acute anal fissure. The effectiveness of the treatment was evaluated in terms of (0 to 2) severity of edema, hyperaemia, local bleeding, purulent necrotic processes, scapular formation, anatomical defect, and a general indicator of the severity of the pathological process (by the sum of the points for all the criteria that were analyzed). The level of proinflammatory PGE2 in serum was determined by the immune enzyme method.Results. The RCCC sample No. 4 showed the most expressive therapeutic effect among the four samples under study, and had credible benefits to the inhibitory effect on purulent-necrotic processes, as expressed by the differences in the overall rate of the pathological process (6 days: 5.83±0.47 points against 7.00±0.37; 7.83±0.31 under the influence of RCCC No. 2, No. 3, respectively, and for 11 days 5.00±1.03 versus 6.83±1.28 points (p=0.08 ) under the influence of RCCC No. 1). The ability of RCCCs No.1 and No.4 to reduce the level of pro-inflammatory PGE2 in blood serum of rats compared with CP in 1.8 and 2.0 times, respectively, contributed to accelerating epithelization and scar formation. The advantages of RCCC No. 4 on the comparison of the ointment "Proctozan" with the reduction of the period of epithelization of the defect of the mucous membrane of the anal canal for 3 days (for 7 days – RCCC No. 4, for 10 days - ointment "Proctozan").Conclusions. The rectal cream of the combined composition No. 4 showed the greatest efficacy, had advantages over the comparison ointment "Proctozan", and is promising for the creation on its basis a new drug for the treatment of anal fissures

Experimental Study of Antimicrobial Properties and Acute Toxicity of the Peo-based Combined Suppositories

Aim. The research of antimicrobial and toxicological parameters of a promising pharmaceutical composition with indole-3-carbinol and meloxicam in the form of rectal suppositories.Materials and methods. The research of antimicrobial activity was carried out in vitro by diffusion in nutrient agar in the modification of "holes" on the reference strains of common pathogens Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Bacillus subtilis, Candida albicans.Adult rats were used for the study of acute toxicity. Suppository mass were administrated in the largest possible volume rectally or orally. The animals were periodically monitored according to the experimental plan – the assessment of physiological parameters before administration and after 6, 12, 18, 24 hours, at 3, 7 and 14 days. The animals were removed from experiment and necropsy provided after 1, 3, 7, and 14 days.Results. The sizes of zones of inhibition of the microorganisms growth were most significant (from 19.27±0.61 mm of E. coli to 40.80±0.42 mm of S. aureus) near sample of the combined composition suppository compared with other combination of active substances and excipients.During the observation of animals for 14 days and the study of internal organs after autopsy, deviations in physiological (weight, temperature, activity, respiratory rate) and macroscopic morphological indicators of animals from reference values were not detected.Conclusion. According to the results of microbiological studies, a moderate antimicrobial effect of suppositories of combined composition in relation to all the studied pathogens was revealed. The absence of manifestations of acute toxicity allows us to conclude that the pharmaceutical composition can be classified as practically non-toxic substances.The obtained results allow us to recommend a pharmaceutical composition with indole-3-carbinol and meloxicam on a polyethylene oxide basis in the form of suppositories for further preclinical studies of specific pharmacological effects as a prostate protective agent

Effect of a Nanodispersion Silica Composite with Polyhexamethylene Guanidine Hydrochloride on Immunological Indicators and Indicators of Oxidation and Antioxidant Homeostasis in Rats with Thermal Burn

Worldwide, nearly 6 million people annually seek medical attention for burn wounds. Today, the main method of local treatment of wounds and burns, including infected ones, is the use of medicines containing antiseptics, antibiotics, sorbents, as well as their combinations.Purpose. To determine the effect of a nanosized silica composite with polyhexamethylene guanidine hydrochloride on the immunological parameters and oxidative-antioxidant homeostasis in the blood and in the lesion of rats with an uninfected thermal burn.Materials and methods. The study was conducted on 72 rats, which were modeled by a thermal burn of the II degree. The animals were divided into 4 groups: intact, control, treated with chlorhexidine, treated with a composite of nanosized silica with polyhexamethylene guanidine hydrochloride. On the 7th, 14th, 21st and 28th day, the animals were removed from the experiment and the immunological parameters and the parameters of oxidative-antioxidant homeostasis in the blood and skin in the lesion were determined.Results. Thermal injury is directly related to biochemical changes in the body. We compared the levels of anti- and pro-inflammatory cytokines, markers of free radical oxidation - diene conjugate (DC), the active products of thiobarbituric acid (TBA-AP), the activity of catalase (Cat) and superoxide dismutase (SOD). It was proved that the NDK + PHMG-GC composite showed significantly more pronounced compared with chlorhexidine, a pharmacological effect in reducing the level of pro-inflammatory cytokines IL-1β and TNF-α and an increase in the content of IL-10 in the blood and the focus of thermal burn during the entire observation period . Also, the composite effectively affects oxidation-antioxidant homeostasis, which is manifested in the normalization of the content of DC and TBA-AP on the 14th day, restoration of Cat activity on the 14th day, SOD - already on the 7th day compared with chlorhexidine.Conclusions. The study indicates that the NDS + PHMG composite has pronounced anti-inflammatory and wound healing properties, which allows it to be used as a combined preparation for the treatment of thermal burn

Influence of Extract of Peach Ordinary (Persica Vulgaris) Leaves on the State of Thymic-lymphatic Element of the Immune System of Rats in Conditions of Chronic Immobilization Stress

The aim – study of the influence of thick extract of peach ordinary (Persica vulgaris) leaves (TEPL) on the state of thymic-lymphatic element of the immune system of rats in conditions of chronic immobilization stress.Materials and methods. The model of chronic immobilization stress was reproduced for 18 days by daily four hour immobilization of rats in tight box. Investigated TEPL, which was obtained at the Department of Chemistry of Natural Compounds of National University of Pharmacy from peach leaves of the Salve variety harvested in Tajikistan was administered intragastrically in a conditionally effective dose of 100 mg/kg. Reference drug the syrup «Immuno-Ton» was used in a dose of 3 ml/kg. The state of thymic-lymphatic element of the immune system in conditions of chronic immobilization stress was determined after the euthanasia of animals under mild inhalation anesthesia by the results of the study of the coefficients of thymus and spleen mass and histological studies on micropreparations, which were prepared according to the generally accepted method. To assess the nature of the effect of the TEPL on the condition of the organs of the rat thymic-lymphatic system under chronic immobilization stress conditions, a comparison was made with intact control and control pathology.Results. It was determined that chronic immobilization stress had suppressive effect on the thymic-lymphatic element of the immune system. An increase in the width of the marginal zone of lymphoid follicles and muft and the number of perivascular lymphatic clusters 1.2 times (p <0.05) compared with control pathology, reduction of signs of stressful hypoxia - the number of structures of white pulp with spasm of the central arteries was noted in the spleen. Reducing the degree of change from the third to fourth phase to the first phase of the accident transformation is set in the thymus, which is confirmed by an increase in the mass of the thymus mass by 2.7% in comparison with the control pathology.Conclusions. The ability of TEPL to restore impaired activity of organs of thymic-lymphatic element of the immune system has been proved. It is likely, that polyphenolic compounds of TEPL exhibit antioxidant properties, enhancing the activity of the antioxidant system, and polysaccharides exhibit immunostimulative properties, the result of which is a stressprotective action. The effectiveness of TEPL was not inferior to the reference drug «Immuno-Ton