The role of topic vaginal products in posthysterectomy vaginal atrophy

Vaginal atrophy represents a frequently encountered condition which is significantly correlated with decreased amounts of circulating oestrogen levels. It is usually characterized by the presence of burning, itching, irritation and dyspareunia. In such cases attention was focused on identifying a topic product which might alleviate these symptoms and stop the deterioration process of the vaginal lining. One product which seems to have an effective role in order to stop this process and to offer a good local control of the disease should contain anti-inflammatory, healing and antiseptic principles. The aim of the current paper is to study the possible benefits of Cerviron a topic product with intravaginal administration which contains seven active principles in order to offer the above mentioned effects.

Optimization of the Tactics of Examination and Treatment of Women of Reproductive Age with Cervical Pathology in Chronic Cervicitis and Vaginitis

The article is a description of the effectiveness of treatment of patients of reproductive age with chronic nonspecific exo-, endocervicitis and vaginitis in the presence of benign and precancerous diseases of the cervix of the uterus of mild degree. Comparative characteristics of the use of the combined preparation for intravaginal administration Elzhina and intravaginal administration of metronidazole with oral fluconazole were carried out. The advantages of using the drug Elzhina in terms of preoperative preparation over the use of radio wave excisional and surgical methods of treatment are noted. The efficacy, tolerability, and safety of the therapy were also evaluated in both treatment options. It is noted that the drug containing ornidazole 500 mg, prednisolone 3 mg, econazole 150 mg, neomycin 65 000 IU, will reduce the severity of inflammatory processes, which has a beneficial effect on the results of radio wave and surgical methods for the treatment of benign and precancerous diseases of the cervix. Against the background of chronic, long-term nonspecific exo-, endocervicitis and vaginitis

Effective, safe and rational pharmacotherapy of endogenic progesterone deficiency

Today, the most frequent complication of pharmacotherapy is an allergic reaction, the so-called drug or drug allergy. An allergic reaction can be caused both by the active ingredients and by the excipients included in the composition of the drug to provide a certain dosage form and its physicochemical properties. Vaginal progesterone preparations are characterized by a large variety of dosage forms: gels, tablets and gelatin capsules for intravaginal administration. It is known that the safety and efficacy of pharmacotherapy depend on the active substance, the dosage form, and the base of the intravaginal preparation, as well as the indices of adherence to medication therapy. At the same time, the base - excipients can cause the development of adverse reactions.The authors of the article, based on an analytical review of domestic and foreign literature, analyzed effective, safe and rational pharmacotherapy of endogenous progesterone deficiency.It is shown that micronization is currently used to improve the bioavailability of natural progesterone – a method of increasing solubility by reducing the particle size of the drug substance. Due to the high solubility of the substance, the risk of possible side effects is reduced, which allows increasing the safety of the drug.The peculiarity of the dosage form for vaginal administration is described. On the basis of the analysis of various forms of progesterone, the clinical efficacy of natural progesterone for vaginal administration has been substantiated.The authors found that the use of progesterone in sublingual and vaginal forms is the most rational in terms of convenience, efficacy and safety.

Development of intravaginal rod insert bearing liposomal raloxifene hydrochloride and Leuprolide acetate as a potential carrier for uterine targeting

Objectives This project aimed at the formulation of dual drug entrapped liposomes held as freeze-dried intravaginal rod insert (IVR), to be administered by vaginal route for uterine targeting. Methods Liposomes were formulated by dehydration–rehydration method using 3 : 1 molar ratio of1,2-distearoyl-sn-glycero-3-phosphocholine : Cholesterol. Characterization was done for vesicle size, zeta potential, entrapment efficiency, surface morphology and % loading. Key findings Spherical and discrete vesicles of size 354 nm were observed in transmission electron microscopy (TEM) image. The entrapment efficiency of 90.91% and 74.3% w/w was obtained for Raloxifene Hydrochloride (RLX) and Leuprolide acetate (LA) respectively. Drug release was sustained for 6 days. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay results showed that dual drug entrapped liposomal formulation show significant cytotoxicity, as also confirmed by higher apoptosis in cell cycle analysis and apoptosis studies (FACS) analysis. Pharmacodynamic studies in New Zealand white female rabbits revealed that intravaginal administration of RLX-LA entrapped liposomal formulation shows considerable fibroid regression. Conclusions Uterine targeting of liposomal RLX-LA suggests its potential to solve the limitations of the presently available therapeutic options.

Modeling of bacterial lipopolysaccharide-induced endometritis in rats and the possibility of its therapy using plasma enriched with soluble platelet factors

We presents results of a study on endometritis modeling in rats with double intravaginal administration of bacterial lipopolysaccharide (LPS). The established endometrial inflammatory process was accompanied by a decrease in the weight of animals, an increase in the weight of the uterus, neutrophilic infiltration, edema, and overexpression of cyclooxygenase in endometrium on 30-45 days after the start of endometritis induction. Local intravaginal use of plasma enriched with soluble platelet factors/platelet-rich plasma (PORFT/PRP) caused a decrease in the intensity of the inflammatory process and the rate of neutrophil infiltration of the endometrium, a decrease in the intensity of cyclooxygenase, interleukin-6 and transforming growth factor-β expression, and an increase in the body weight of animals. The conclusion was made on the possibility of creating model of endometritis in rats by double administration of LPS and the ability of local administration of PORFT/PRP to have a therapeutic effect on the inflammatory process in the endometrium.

Pregnancy loss. Treatment options

Objective. To justify the selection of the most effective gestagen with an optimal safety profile in the treatment of patients with pregnancy loss. Patients and methods. A retrospective study of 93 records of patients with recurrent pregnancy loss (RPL) who were prescribed gestagens was made. The first group included 49 patients taking dydrogesterone; the second – 44 patients who received micronized progesterone (19 – orally/subgroup 2a/ and 25 – intravaginally/subgroup 2b/). In order to assess the effectiveness of therapy, prolongation of pregnancy up to 22 weeks was the study’s primary endpoint. The secondary endpoint was prolongation of pregnancy up to 34 weeks of gestation and live birth. Results. A positive subjective evaluation was found in 94% of women taking dydrogesterone and in 79.5% of women taking micronized progesterone (68.4% – orally and 88% – intravaginally). The total number of observations with adverse effects when taking dydrogesterone was significantly lower than in case of micronized progesterone: in 7 (16%) and 31 (72%), respectively (p < 0.05). Dull lower abdominal pain was significantly more frequent in oral administration of micronized progesterone compared with dydrogesterone: in 15 (79%) and 11 (22%), respectively (p < 0.05). In dydrogesterone and intravaginal administration of micronized progesterone, pain syndrome occurred with the same frequency. Bloody vaginal discharge was 2.5 times more frequent in group 2: in 4 (8%) patients of group 1 and in 10 (23%) patients in group 2 (p < 0.05). Moreover, bloody discharge remained significantly more often in case of vaginal administration of micronized progesterone (p < 0.05). In oral micronized progesterone, the difference with dydrogesterone was not significant. According to ultrasound data, hematomas that were not accompanied by bloody discharge were registered in 6 (12%) patients taking micronized progesterone, equally for oral and intravaginal administration. Against the background of receiving dydrogesterone, no hematomas were revealed according to ultrasound data. Against the administration of dydrogesterone, both primary and secondary results were achieved in all women. With the use of micronized progesterone, the primary result was achieved in 39 (88.6%), the secondary – in 38 (86%) patients. Early pregnancy loss was in 6 (14%) women of group 2: 5 (11%) had a spontaneous miscarriage before 14 weeks of gestation (intravaginal drug administration), one had premature birth at 32 weeks (oral drug administration). Conclusion. Dydrogesterone has the highest efficacy and optimal safety profile in the treatment of RPL; therefore, it can be considered as the gestagen of choice in early pregnancy. If it is impossible to prescribe dydrogesterone, preference should be given to micronized progesterone – intravaginal route of administration. Key words: dydrogesterone, micronized progesterone, pregnancy loss, progesterone

Evaluation of the effect of excess and deficiency of serum hydrogen sulfide on the condition of the vaginal wall of intact rats

Various pathological conditions can be characterized not only by a decrease or increase in basal levels of hydrogen sulfide in the serum, but also the levels of hydrogen sulfide can modulate the course of the pathological process. The impact of serum hydrogen sulfide on the condition of the intact vaginal wall of rats was evaluated in this study. The aim of the study was to evaluate the effect of excess and deficiency of serum hydrogen sulfide on the condition of the vaginal wall of intact rats. The study was performed on 75 female Wistar rats under 1 year of age and weighing 160.0 to 200.0 grams. All animals were divided into 6 groups: control (intact rats); experimental 1 (H2S excess); experimental 2 (H2S deficiency); experimental 3 (intravaginal administration of suppositories with clindamycin); experimental 4 (H2S excess + suppositories with clindamycin); experimental 5 (H2S deficiency + suppositories with clindamycin). The levels of serum hydrogen sulfide were studied, as well as microscopic examination of the structure of the vaginal wall and determination of the levels of TNF-α and IL-1β in tissue homogenate were performed. In experimental groups 3, 4 and 5 all studies were performed in dynamics – 10 minutes, 4, 8 and 24 hours after a single intravaginal administration of clindamycin phosphate. The data were processed using the statistical software package SPSS 20.0 for Windows. Under conditions of both hydrogen sulfide deficiency and excess, no statistically significant changes in TNF-α and IL-1β levels in the vaginal wall of intact rats were observed. Also, no changes in the histological structure of the wall were found. Similar data were demonstrated in experimental groups 3, 4 and 5. This picture is explained by the fact that hydrogen sulfide affects various parts of the inflammatory process, while reducing the production of inflammatory mediators. In intact tissues, in the absence of an inflammatory process, there is no point of application of hydrogen sulfide, and therefore no significant changes are observed. Thus, both excess and deficiency of serum hydrogen sulfide do not affect the condition of the vaginal wall of intact rats.