Suppositories Research Articles

Local management strategies for inflammatory vaginitis in dermatologic conditions: Suppositories, dilators, and estrogen replacement

Prevalence of vaginal involvement in erosive lichen planus and pemphigus vulgaris has been reported in over 58% and up to 44% of patients, respectively.1Khurana A. Tandon S. Marfatia Y.S. Madnani N. Genital lichen planus: an underrecognized entity.Indian J Sex Transm Dis AIDS. 2019; 40: 105-112Crossref PubMed Google Scholar,2Kavala M. Topaloğlu Demir F. Zindanci I. et al.Genital involvement in pemphigus vulgaris (Pv): correlation with clinical and cervicovaginal Pap smear findings.J Am Acad Dermatol. 2015; 73: 655-659Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar While most dermatologists are comfortable utilizing ultrapotent steroids on the vulva, less are comfortable with managing vaginal inflammation. Here, we highlight 3 local strategies to target inflammatory vaginal dermatoses and prevent scarring (Fig 1). We recommend starting with 25-mg hydrocortisone acetate suppositories, available as rectal suppositories. Patients should be counseled to use vaginally instead of rectally. Suppositories are initiated nightly for 2 to 4 weeks and decreased to every other night, or 2 to 3 times per week depending on disease control. Patients should be evaluated monthly, and suppositories should be tapered to the lowest dose/frequency that maintains disease remission.2Kavala M. Topaloğlu Demir F. Zindanci I. et al.Genital involvement in pemphigus vulgaris (Pv): correlation with clinical and cervicovaginal Pap smear findings.J Am Acad Dermatol. 2015; 73: 655-659Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar If more potent suppositories are required, hydrocortisone can be compounded at doses of 100 to 200 mg. When prescribing suppositories, we recommend candidal prophylaxis, with topical antifungals 2 to 3 times per week or oral fluconazole 150 to 200 mg weekly. Insertion of dilators 3 times, weekly, to prevent adhesions. Dilators can be ordered online and come in sets of varying sizes. Patients should use the largest dilator comfortable, and vaginal moisturizers and lubricants can be utilized. Estrogen deficiency should be considered in postmenopausal patients as this can contribute to vaginal inflammation. Local estrogen therapy includes a ring, tablet, or cream. Generally, vaginal cream tends to have the least pain with insertion and is used nightly for 2 weeks with decrease to maintenance 1 to 3 times per week. None disclosed.

Smart Self-Nourishing and Self-Healing Artificial Skin Composite Using Bionic Microvascular Containing Liquid Agent.

Artificial skin composites have attracted great interest in functional composite materials. The aim of this study was to prepare and characterize a smart artificial skin composite comprising a bionic microvascular with both self-nourishing and self-healing functions. A poly(vinyl alcohol)–glycerol–gelatin double network organic hydrogel was used as the artificial skin matrix. The hydrogel had high mechanical strength because of the strong hydrogen bond formed between the PVA and glycerol (GL). The gelatin (GEL) increased the toughness and elasticity of the hydrogel to ensure the strength of the artificial skin and fit of the interface with the body. The bionic polyvinylidene fluoride (PVDF) microvascular had excellent thermal stability and mechanical property in artificial skin. Results indicated that self-nourishing was successfully realized by liquid release through the pore structures of the bionic microvascular. The bionic microvascular healed microcracks in the artificial skin when damage occurred, based on a self-healing test.

Enhancement the eff ec- tiveness of therapy of the new COVID-19 coronavirus infection using interferon alpha-2b in adults

In order to assess the clinical eff ectiveness of COVID-19 complex therapy in adults, 140 patients with a confi rmed diagnosis of a new coronavirus infection, clinical symptoms and lung damage from 25 to 75 % (mild and moderate form) hospitalized in budgetary healthcare institutions of the Omsk region were included in an open prospective observational study. Patients were evenly divided into two groups: 1 — received standard therapy in accordance with the Temporary Guidelines "Prevention, diagnosis and treatment of new coronavirus infection (COVID-19)" approved by the Ministry of Health of the Russian Federation and interferon alpha-2b preparations (Viferon ® rectal suppositories 3,000,000 IU and Viferon ® gel for external and topical use of 36,000 IU/g); 2 — received only standard therapy. In group 1 patients, elimination of the SARS-CoV-2 antigen from the nasopharyngeal mucosa occurred 2 days earlier than in group 2 patients. Also, patients receiving standard therapy and interferon alpha-2b preparations improved on average 4.5 days earlier, most of the main symptoms of the disease were stopped by the 6th day of therapy. It was noted that in patients receiving complex standard therapy with adding of interferon alpha-2b preparations, a more pronounced regression of lung tissue damage was observed, especially in patients with a high degree of their lesion according to CT data before hospitalization. By the end of treatment in group 1, the proportion of patients with lung tissue lesions of grade CT-3 signifi cantly decreased by 17%, while in group 2, the proportion of patients with CT-3 increased by 13 %. Analysis of the dynamics of laboratory parameters and the main markers of infl ammation in the therapy groups also confi rms the positive eff ect of the inclusion of interferon alpha-2b drugs in the standard therapy. No adverse events associated with the use of interferon alpha-2b preparations were registered. Thus, in patients receiving standard therapy and interferon alpha-2b preparations, recovery occurred in a shorter time. In the end, this contributed to a faster discharge from the hospital and a reduction in the burden on the bed fund and medical staff . The results obtained give grounds to recommend the inclusion of interferon alpha-2b preparations (Viferon ® rectal suppositories 3,000,000 IU and Viferon ® gel for external and topical use 36,000 IU/g) in standard COVID-19 therapy regimens in adult patients with mild and moderate forms of the disease.

FORMULATION OF MESALAMINE-LOADED RECTAL MUCOADHESIVE PELLETS FOR THE TREATMENT OF INFLAMMATORY BOWEL DISEASE USING 32FULL FACTORIAL DESIGN

Objective: The objective of the present work was to optimize a rectal suppository containing mucoadhesive pellets of Mesalamine to achieve local yet sustained release of Mesalamine for once-a-day administration for the therapy of Inflammatory Bowel Disease. Methods: Thus, the present work involves forming mucoadhesive pellets of mesalamine by extrusion spheronization, which were then loaded into a suppository to be administered rectally. The pellets were evaluated for mucoadhesion strength, swelling potential, morphology, particle size, drug release, drug loading and retention time. Results: The optimized batch of pellets using Eudragit RLPO as the release retardant, carrageenan as a mucoadhesive polymer and other excipients had a mucoadhesion strength of 0.143 N, a swelling index of 50.50 %, and 44 % and 75 % drug was released from them at the end of 6 and 15 h respectively. The pellets-loaded cocoa butter suppositories had a melting range of 35–37 °C, disintegrated within 8–9 min and had a hardness of 4–5 kg/cm3. A comparison of the in vitro drug release profile from the mucoadhesive pellets and the mucoadhesive pellets-loaded suppositories showed a closeness in the % cumulative drug release indicating that cocoa butter did not interfere in the release of the drug from the pellets. Conclusion: Mucoadhesive Pellets were successfully developed by extrusion spheronizer technique and incorporated into suppositories. In vitro study revealed a release profile that warranted a once-a-day regimen leading to a reduction in the requirement of the drug and hence the side effects.

Extrapyramidal syndrome in a breastfed child, relevance of toxicological analysis

The passage of drugs in breast milk may be responsible for toxicity in breastfed children. We report here a case of passage of metoclopramide, an antiemetic neuroleptic, in breast milk, causing an extrapyramidal syndrome in the child, revealed in blood and hair. Case: a 21-week-old child was brought by his parents to the pediatric neurology department for consultation following two episodes of unexplained extrapyramidal syndrome. The little G., fed by mixed breastfeeding, presented a first episode of unexplained acute dystonia (generalized hypertonia with legs in extension and arms flexed against the chest, ceiling gaze, opisthonos) and two weeks later, a new episode of acute extrapyramidal syndrome, which resolved in a few hours. Both events required emergency hospitalization. During the second episode, diazepam 0.5 mg/kg IV was initiated, unsuccessfully. The anamnesis revealed that the mother had taken a rectal suppository of metoclopramide (10 mg) 48 hours before the first episode. An MRI was performed on arrival at the emergency room. Blood toxicology analysis was performed two days after the first episode. A 3-cm strand of brown hair was collected one month after the second episode. The entire sample (13 mg) was analyzed without segmentation. It should also be noted that the father had retractile capsulitis, treated with codeine paracetamol, and that the child had received paracetamol for teething. The child had no further episodes of dystonia since the second event. The MRI was normal. The child's blood toxicology analysis revealed the presence of metoclopramide at a concentration of 8 ng/mL. Hair analysis revealed metoclopramide at a relatively high concentration (1058 pg/mg), as well as paracetamol (31 ng/mg), lidocaine (34 pg/mg), diazepam (3 pg/mg) and its metabolite nordazepam (5 pg/mg), and codeine (16 pg/mg) in the analyzed hair of child G. The presence of diazepam and its metabolite can be explained by medical care. The low concentration of codeine without its metabolite morphine, may suggest an external contamination by the environment, contact with people who had consumed this molecule (bedding, caressing, etc.), especially the child's father. The presence of metoclopramide in the blood and hair is compatible with a passage of breast milk to the child. According to the literature, less than 5% of the maternal dose is found in the child. Adverse effects such as intestinal disorders, drowsiness, agitation, hypertonia have already been described in breastfed children (EMA. Metoclopramide Assessment report, 2013). This case illustrates the passage into breast milk of rectally administered metoclopramide in the mother and the toxic effects of this molecule in the child. The interpretation of hair analysis in infants remains nevertheless delicate to discriminate consumption from environmental contamination.

Interferons alpha and gamma, pidotimod, and tilorone in the treatment of acute respiratory infections in patients with allergic rhinitis: a prospective, cohort clinical and immunological study

Aim. To compare the clinical efficacy and influence on interferon (IFN) production / sensing of drugs with immunemediated antiviral effects, which potentiate type 1 (T1) immune responses, in the treatment of acute respiratory infections (ARI) in patients with allergic rhinitis.Materials and methods.146 ARI patients with remission of seasonal allergic rhinitis were divided into 4 cohorts. In addition to symptomatic therapy, patients received either 2,000 IU of IFNγ in each nasal passage 5 times a day; or rectal suppositories containing 106 IU of IFN-α2b and antioxidants (AO) twice a day, and a gel with IFN-α2b and AO intranasally 3 times a day; or 400 mg of pidotimod per os twice a day; or 125 mg of tilorone per os on days 1, 2, 4, and 6. The severity of ARI was determined daily as the sum of 10-point scores for 15 symptoms. Serum concentrations of IFNα and IFNγ and the ability of blood cells to produce these cytokines ex vivo spontaneously and upon stimulation with Newcastle disease virus or phytohemagglutinin were studied using enzyme-linked immunosorbent assay (ELISA). The proportions of circulating lymphocytes expressing type I IFN receptor subunit 2 (CD118) or IFNγ receptor α-chain (CD119) were determined by flow cytometry.Results. ARI symptoms in all cohorts generally regressed in a similar way. However, from day 5 of the treatment, pidotimod relieved symptoms more effectively than other drugs. In patients treated with tilorone, the regression of ARI manifestations was delayed in the first two to three days, followed by rapid symptom reduction. An initial decrease in the induced production of IFNγ was found in patients treated with pidotimod, and a tendency to a decrease in this parameter was noted in other cohorts. The induced production of IFNγ after the treatment in all groups did not differ from that in healthy donors. No significant changes and differences in the proportions of CD118+ and CD119+ lymphocytes were found between the cohorts, except for a decrease in the number of CD118+ cells after the treatment with tilorone. In patients treated with IFN-α2b + AO, the proportions of CD119+ and CD118+ lymphocytes tended to increase slightly.Conclusion. Drugs that promote the development of T1 over T2 immune responses are a useful option for treating ARI in patients with allergic rhinitis.

Formulation Design and Evaluation of Hydrocortisone Gel for Topical Use

Hydrocortisone is a corticosteroid drug used for topical atopic dermatitis treatment available in the form of a spray, rectal cream, powder for preparation and injection, ointment in concentrations: 0.5, 1, 2.5%, ear solution 1%, topical solution in concentrations: 0.1, 2.5%, rectal suppositories, suspension solution plus tablets. Hydrocortisone gel was manufactured and evaluated in-vitro model by examining the physical and chemical properties, as well as evaluating the rheological properties with a texture analyzer, also evaluated. The stability of accelerated hydrocortisone gel, thermal, chemical and acid stability of the components were also evaluated. The feasibility study was also completed. All of these evaluations were compared relative to the commercial formulas and statistical analyzes were conducted. The results of hydrocortisone gel compared to the commercial formula showed optimum physicochemical properties, good rheological properties, and good stability. From the general results, we can conclude that hydrocortisone gel is a practical, more effective, safe and stable formulation when compared to its counterparts.

Agreement of telemetric temperature capsules ingested 48 hours apart

Telemetric temperature capsules are frequently utilized to measure deep body temperature. Whereas most methods to measure temperature are conducted at a single site (e.g., rectal temperature), the location of ingested telemetry capsules varies. If distinct regions of the gastrointestinal tract have different temperatures, the measurements obtained using telemetry capsules will vary accordingly. This study examined the agreement of two telemetric temperature capsules in fifty-seven Army Ranger School students ingested 64 and 16 h before a cool weather waterborne movement. Twenty-one subjects (37%) (age: 25 ± 4, weight: 81±7 kg) retained both capsules. Subjects completed activities that could increase (e.g. exercise) and decrease (e.g. cold water immersion) body temperature. Agreement between the two capsules was assessed through concordance and Bland Altman analysis using a linear mixed model. Bias between the two capsules was low (0.01 °C, SE = 0.03, before a neck-deep immersion river crossing and −0.09 °C, SE = 0.08, after the river crossing), but there were large differences in the variance components (0.044 vs 0.155 total variance for the pre-crossing vs the post-crossing data). The 95% Limits of Agreement indicate that discordance between the two capsules was lower before the river crossing (−0.40 to +0.42 °C) than after (−0.86 to +0.68 °C). In summary, this study examined telemetry capsule agreement with more time between capsule ingestion (48 h) in a larger sample size than most previous studies on the topic, and found notable (95% LoA>0.4 °C) variability between the two capsules which was exacerbated after crossing a cold river. Differences in gastrointestinal location of telemetry capsules can introduce variability into the measurement of deep body temperature due to regional temperature differences. This variability may be acceptable for some study designs, but unacceptable when small changes in temperature are important to detect. If the convenience of telemetric temperature capsules is desired, an alternative is to use the capsule as a rectal suppository.

Intrarectal diazepam following pelvic reconstructive surgery: a double-blind, randomized placebo-controlled trial

Patients undergoing vaginal hysterectomy with native tissue pelvic reconstruction typically have low pain levels overall in the postoperative period. Notwithstanding, pain control immediately after surgery may be more challenging and a barrier to same-day discharge. Intrarectal diazepam has been used for acute and chronic pelvic pain and has a pharmacokinetic profile ideal for intermittent use. However, its use has not been investigated after the surgical intervention. This study aimed to evaluate the effect of diazepam rectal suppositories on early postoperative pain after hysterectomy and vaginal reconstruction for pelvic organ prolapse. This was a double-blind, randomized, placebo-controlled trial comparing postoperative pain scores after vaginal hysterectomy with native tissue prolapse repairs. Patients were randomized to receive either an intrarectal 10-mg diazepam suppository or an identical placebo. Moreover, the participants completed the questionnaires at baseline, the morning of postoperative day 1, and 2 weeks after the operation. Surveys included visual analog scales for pain, a validated Surgical Satisfaction Questionnaire, and queries regarding medication side effects and postoperative recovery. The primary outcome was pain scores based on a visual analog scale approximately 3 hours after surgery. The secondary outcomes included total morphine equivalents after surgery, patient satisfaction with pain control, same-day discharge outcome, and overall satisfaction. The chi-square, Fisher exact, and Mann-Whitney tests were used. Based on a 10-mm difference in postoperative vaginal pain using the visual analog scale, sample size was calculated to be 55 patients in each arm to achieve 80% power with an alpha of.05. From February 2020 to August 2021, 130 participants were randomized. Of those participants, 7 withdrew, and 123 were analyzed: 60 in the diazepam group and 63 in the placebo group. The median age was 65 years (interquartile range, 27-80), the median body mass index was 27.9 kg/m2 (interquartile range, 18.70-45.90), and 119 of 123 participants (96.7%) were White. There was no difference in the baseline characteristics, prolapse stage, or types of procedures performed between groups. Most participants had concurrent uterosacral ligament suspension with anterior and posterior repairs. Of note, 50 of 123 participants (41%) had midurethral slings. Moreover, 61 of 123 participants (50%) were discharged on the day of surgery. There was no difference in the primary outcome of vaginal pain 3.5 to 6.0 hours postoperatively (25 vs 21 mm; P=.285). In addition, the amount of rescue narcotics used in the immediate postoperative period (19.0 vs 17.0 MME; P=.202) did not differ between groups. At 2-weeks postoperatively, patients in the placebo group reported higher satisfaction with pain control in the hospital (31 vs 43 mm; P=.006) and pain control at home (31 vs 42 mm; P=.022). No difference was noted between same-day discharges and those who were admitted overnight. The placement of a 10-mg diazepam rectal suppository immediately after pelvic reconstructive surgery did not improve pain or narcotic usage in the early postoperative period. Although the placebo group reported slightly higher satisfaction with pain control 2 weeks after surgery, overall pain levels were low. Therefore, we do not believe that the addition of diazepam to the postoperative regimen is warranted.

Development and validation of HPLC-DAD and LC-(ESI)/MS methods for the determination of sulfasalazine, mesalazine and hydrocortisone 21-acetate in tablets and rectal suppositories: In vitro and ex vivo permeability studies

Controlled-release tablets and rectal suppositories of sulfasalazine (SLF) and hydrocortisone 21-acetate (HA) were prepared as recommended dosage forms for the treatment of acute episodes of ulcerative colitis, in patients who do not respond to monotherapy.A High-Performance Liquid Chromatography (HPLC) Diode-array method with a gradient elution mobile phase was developed to evaluate the production quality of both formulations (assay and dissolution profiles in gastric and intestinal fluids). Method's validation was carried out providing good linearity (r ≥ 0.9995), precision (RSD < 1.53%), recovery (96.9% − 103.7%) and limits of detection (LODSLF = 12 ng/mL, LODHA = 15 ng/mL). Experimental design and Plackett-Burman methodology was constructed to study the robustness of the analysis. In all composite substrates, a freezing lipid precipitation approach was used as purification step. The method was optimized by applying Central Composite design mode.The in-vitro/ex-vivo permeability studies of both formulations were evaluated by a Liquid Chromatography-Electron Spray Ionization Mass Spectrometry (LC-ESI/MS) +/- mode. The analysis of sulfamethazine (internal standard, SLM, m/z 279), HA (m/z 449, [M + HCOO]-), SLF (m/z 399) and its active metabolite mesalazine (MSL, m/z 154) was performed using a C18 column and gradient elution. The validation of the method met the requirements of the International Council for Harmonization (ICH) (r ≥ 0.9997, RSD ≤ 4.62%, Recovery > 95%, LODSLF = 1.28 ng/mL, LODHA = 1.07 ng/mL, LODMSL = 3.16 ng/mL). Based on the results, important conclusions were drawn concerning the role of excipients and SLF metabolism.

Research on the composition development of suppositories with echinacea and study of their stability

The purpose of the work was to experimentally substantiate the composition and study the stability of extemporal suppositories with Echinacea, intended for use in complex therapy and prevention of genitourinary diseases.&#x0D; Materials and methods. The object of the study was samples of suppositories made by pouring using liquid Echinacea extract as an active pharmaceutical ingredient. Cocoa butter, Witepsol H15 and Witepsol W35 were used as suppository bases. The study was carried out using modern physicochemical, pharmaco-technological and microbiological methods.&#x0D; Results. On the basis of the carried out physicochemical and pharmaco-technological studies, it was found that in the manufacture of suppositories using liquid Echinacea extract, Cocoa butter or Witepsol can be used as a suppository bases. The main indicators of the quality of suppository samples were also studied: organoleptic characteristics, average weight, melting point, time of complete deformation, microbiological purity, meeting the requirements of the State Pharmacopoeia.&#x0D; Conclusions. As a result of the carried out physicochemical, pharmaco-technological and microbiological studies, a suppository base was selected for the creation of extemporal suppositories for the treatment and prevention of genitourinary diseases, the main quality indicators were established that meet the requirements of the State Pharmacopoeia of Ukraine, and the shelf life of the suppositories is 10 days.

Rectal diclofenac; an effective modality for pain relief after vaginal birth

&lt;p&gt;&lt;strong&gt;Background and Objective:&lt;/strong&gt; Vaginal delivery (VD) is the safest delivery option for the mother and is associated with quick recovery and minimal maternal morbidity and mortality. However, one of the commonest fears among women about VD is pain. This study aims to assess the effectiveness of diclofenac suppositories (per rectum) compared to the intramuscular diclofenac for the pain relief in females after VD.&lt;br /&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This prospective comparative was study conducted at the Emergency Section (labor room) of Obstetrics &amp;amp; Gynecology Department in one of the tertiary care teaching hospitals of Lahore, Pakistan. A total of 182 female patients undergoing VD were selected and further divided into group A and group B. Group A was administered rectal analgesia in the form of rectal suppositories (100 mg) immediately after perineal tear (first and second degree only) repair and repeated after 6 hours. While group B received one injection of intramuscular diclofenac, immediately after perineal tear repair. The pain score was measured on a graphical score using Graphic Rating Scale, immediately at rest, during movement, and during urination. The pain score was reassessed after 6 hours with the same parameters and compared between both groups.&lt;br /&gt;&lt;strong&gt;Results:&lt;/strong&gt; The overall pain score was significantly lower immediately (p = 0.004) and 6 hours (p = 0.002) after VD in group A at rest, during movement, and during urination as compared to group B.&lt;br /&gt;&lt;strong&gt;Conclusion:&lt;/strong&gt; The use of rectal diclofenac suppositories is a simpler and more effective and acceptable method of reducing the pain experienced by the women following perineal trauma after vaginal childbirth.&lt;/p&gt;

Effectiveness of Experimental Colitis Therapy with Original Vitamin D3 Rectal Suppositories

Background: Pathogenesis of inflammatory bowel disease (IBD) is insufficiently explored, while most of the therapeutic agents used for IBD cases have undesirable side effects, which restrict their administration.The aim of this research was to study the influence of vitamin D3 formulated into original rectal suppositories on the parameters of clinical score, morphology, and oxidative lipid and protein destruction in the colonic lesion in the cases of experimental colitis (EC). Methods and Results: The experiment was performed on 98 Wistar male rats weighing 210-230 g. EC condition was induced by two-phase administration (dermal application and per rectum) of 3% alcohol solution of oxazolone. Originator polyethylene glycol-based suppositories, which contained 1500 МЕ of vitamin D3, were administered per rectum every 12 hours. Clinical score was defined according to the Disease Activity Index (DAI) scale. Morphometry was run using the software program “ImageScope M” (Russia). Damage of the colonic tissue was estimated on Tissue Damage Index (TDI). The following parameters were determined in the colonic lesion: neutrophil count (NC), lymphocyte count (LC), eosinophil count (EC), histiocyte count (HC), plasma cell count (PC), fibroblast count (FC), the diameter of the ulcerous defect, TDI, MPO expression, and TNF-α expression. The following parameters were determined in the damaged tissue homogenate: lipid peroxidation product count (LPP) and protein oxidative modification (POM) count. In cases of oxazolone-induced EC, on Days 2, 4, and 6, we registered clinical and laboratory signs, an ulcerous defect in the damaged area of the colon, all of which are typical for IBD conditions. There was an increase in DAI (peak on Day 6) and TDI (peak on Day 2). We also found an increase in NC (peak on Day 2), LC (peak on Day 6), EC (peak on Day 2), PC (peak on Day 2), HC (peak on Day 2), and FC (peak on Day 2). There was an increase in MPO expression (peak on Day 2) and TNF-α expression (peak on Days 2 and 4). We observed increases in the primary, secondary, and end LPP counts and the early-phase and late-phase POM counts in spontaneous and induced modes. An administration of 1500ME vitamin D3 rectal suppositories every 12 hours for 6 days decreased the severity of clinical manifestations and DAI. It reduced the area of the ulcerous defect and decreased the TDI on Days 4 and 6 of the experiment. On the background of using vitamin D3 rectal suppositories, we found a decrease in NC, EC, LC, and PC in the damaged area and an increase in HC and FC on Days 2, 4, and 6 from the start of the experiment. Administration of D3 rectal suppositories decreased МРО expression and TNF-α expression on Days 4 and 6 of EC. In the damaged area of the colon, we observed a decrease in the counts of the primary, secondary, and end LPP on Days 4 and 6 of the experiment. We also documented a decrease in the POM count in spontaneous mode on Day 2 and on Day 6 in induced mode. Conclusion: Vitamin D3 as a constituent of originator rectal suppositories in total dose 18,000 МЕ in the pre-clinical phase of EC decreases the intensity of EC clinical manifestations. It reduces the count of the cells that take part in tissue destruction in the colonic wall, of TNF-α and MPO expression levels, and LPP- and POM product count. It increases the count of the cells, which promotes tissue reparation. The obtained results are essential for carrying out further research aimed at elaboration of the mechanism of the D3 effect in cases of IBD and at its possible clinical use.

Comprehensive study for the development of rectal suppositories with diosmin and hesperidin

The aim. To conduct a comprehensive study of biphasic-type suppositories that contain diosmin and hesperidin.&#x0D; Materials and methods. Samples of biphasic-type suppositories with a mass of 4.0 were objects of the study. Pharmacological, technological and analytical research methods were used to directly or indirectly analyze the strength and completeness of the drug activity. Thus, in this work we combined the study of the specificity of the pharmacological action of the drug, experimental verification of the quantitative content of API, analysis of the structural properties of suppositories and study of the profile of the release of active pharmaceutical ingredients.&#x0D; Results. Therefore, based on the obtained data, the most effective dose was 75 mg / kg (in terms of a human dose of 300 mg per suppository). The drug in the selected dose showed a significant therapeutic effect, which significantly exceeded that of the test sample at a lower dose and the reference agent. According to the results of technological studies, it was determined that all samples of suppositories had satisfactory structural and mechanical properties. Studies of the histological structure of the mucous membrane of rats proved that there is a positive effect of treatment with suppositories with diosmin and hesperidin due to the improvement of the normal condition of the mucous membrane, the absence of edema and ulcerative defect. Research of the release profile of active pharmaceutical ingredients showed that the best percentage of release is characteristic of sample 2 (99.8 %)&#x0D; Conclusions. Therefore, suppositories with diosmin and hesperidin in therapeutically dose of 75 mg/kg of animal weight can be used for further research and will be of interest in the treatment of hemorrhoids of both acute and chronic forms

Development and optimization of quantitative composition of rectal suppositories with diosmin and hesperidin by the method of mathematical planning of the experiment

In the development of suppositories biphasic media are rarely used. It is due to the occurrence of possible instabilities within the system «dispersed phase and a dispersing medium». To solve such problems, it is rational to use the methods of mathematical planning of the experiment. The method of mathematical planning of the experiment feature is the diversity of approaches to model construction. This means that these methods are theoretically predict the results of a future experiment, analyze the data obtained, prevent the repetition of experiments and optimize the technology of medicine.&#x0D; The aim of the present research was to develop and optimize of quantitative composition of rectal suppositories with diosmin and hesperidin by the method of mathematical planning of experiment.&#x0D; Objects of the study were samples of suppositories of the biphasic type with diosmin and hesperidin. The dispersing medium of these samples consisted of hydrophobic (Witepsol W35 and emulsifiers) and hydrophilic parts (sodium alginate gel with the addition of Ca2+ as a complexing cation). Preliminary results of determining the percentage limits of the hydrophobic part of the dispersed medium were carried out by studying the indicators of the release of active substances from the dosage form and the laser diffraction method. As responses of experiments was used such indicator as: disintegration time, hardness and mucoadhesion.&#x0D; As a result of the studies, the functional dependence of the indicators on the amount of components of the suppository dispersed medium was established. It was found that acceptable values of the responses should conform to the following conditions: hardness and mucoadhesion should be close to the maximum, and the disintegration time – to the minimum.&#x0D; According to the results of the study it was found that the optimal content of the mixture of emulsifiers – 6.29%, solid fat – 39.51%, the hydrophilic part of the biphasic medium – 29.58%. Responses that will provide the system with the necessary structural-mechanical and pharmaco-technological properties are within: y1 (2.713); y2 (22.639); y3 (439.283). The obtained data will be used in further studies to optimize the composition and technology of rectal suppositories with diosmin and hesperidin.

Impact of intrarectal diazepam on early postoperative pain following pelvic reconstructive surgery: a double-blind, randomized placebo-controlled trial

To evaluate the effect of diazepam rectal suppositories on early postoperative pain following hysterectomy and vaginal reconstruction for pelvic organ prolapse. In this institutional review board approved, double-blind, randomized placebo-controlled trial, eligible patients were those scheduled to undergo a total vaginal hysterectomy with reconstructive surgery for prolapse. Consented patients were randomized to receive either a 10mg diazepam rectal suppository or an identical appearing placebo intraoperatively at the completion of surgery. Our primary outcome was vaginal pain 3.5-6 hours postoperatively utilizing the 100mm visual analog scale (VAS). Participants also completed surveys regarding pain at baseline, the morning of postoperative day (POD) one, and two-weeks postoperatively. Secondary outcomes included total morphine equivalents following surgery, patient satisfaction with pain control, and overall satisfaction. Chi-squared test, Fisher’s exact test, and Mann-Whitney test were utilized. Our sample size calculation demonstrated that 55 patients per arm were required to detect a difference in our primary outcome. From February 2020 to August 2021, 130 subjects were randomized. Seven patients withdrew, 113 have been analyzed to date; 57 in the diazepam group, 56 in placebo. The median age was 65 (IQR 27, 80), median BMI was 27.9 (IQR 18.70, 45.90), and 96.5% (n=109) of participants were white. There were no differences in baseline characteristics, prolapse stage, or types of procedures performed between groups. Ninety-nine percent (n=112) of participants had concurrent uterosacral ligament suspension, anterior and posterior repairs. Forty-one percent (n=46) had midurethral slings. Forty-five percent (n=51) had same-day discharge. There were no differences in the amount of intraoperative lidocaine injected (30.84 vs 30.16mL, p=0.679) or amount of rescue narcotics used in the immediate postoperative period (22.5 vs 16 morphine equivalents, p=0.286). There was also no difference in the primary outcome of VAS score for vaginal pain 3.5-6 hours postoperatively (24 vs 21mm, p=0.417). At their 2-week survey, patients in the placebo group reported higher satisfaction with pain control in the hospital (31 vs 41mm, p=0.012) and pain control at home (31 vs 40mm, p=0.043). No differences were noted among patients discharged on POD0 compared to those admitted overnight. In our population, placement of a 10mg Diazepam rectal suppository immediately following pelvic reconstructive surgery did not improve pain or narcotic usage in the early postoperative period. Although the placebo group reported slightly higher satisfaction with pain control two-weeks following surgery, overall pain levels were low. Therefore, we do not feel the addition of diazepam to the post-operative regimen is warranted.

Readiness of the Kenyan public health sector to provide pre-referral care for severe paediatric malaria.

ObjectiveTo assess readiness among primary public health facilities in Kenya to provide pre‐referral antimalarials for severe malaria.MethodsNine national surveys of randomly selected primary public health facilities undertaken bi‐annually between 2017 and 2021 were analysed. The outcomes included the availability of pre‐referral antimalarial drugs at the health facilities and health worker knowledge of recommended pre‐referral treatment for severe malaria.ResultsA total of 1540 health workers from 1355 health facilities were interviewed. Injectable artesunate was available at 46%, injectable quinine at 7%, and artemether at 3% of the health facilities. None of the facilities had rectal artesunate suppositories in stock. A total of 960 (62%) health workers were trained on the use of injectable artesunate. 73% of the health workers who had ever referred a child with severe malaria were aware that artesunate was the recommended treatment, 49% said that intramuscular injection was the preferred route of administration, and 60% stated the correct dose. The overall knowledge level of the treatment policy was low at 21% and only slightly higher among trained than untrained health workers (24% vs 14%; p < 0.001) and those with access to guidelines versus those without access (29% vs 17%; p < 0.001).ConclusionsThe readiness of primary health facilities and health workers to deliver appropriate pre‐referral care to children with complicated malaria in Kenya is inadequate. Further investments are required to ensure (a) availability of nationally recommended pre‐referral antimalarials; (b) appropriate training and supervision in their administration, and (c) monitoring of the entire referral process.

Study of the local irritating effect of suppositories with gabutamine

In the practice of anticonvulsant therapy, a significant arsenal of drugs is used. In recent years, it has been established that nitrogen-containing derivatives of trichloromethylpropanoic acid are mainly low-toxic compounds with pronounced anticonvulsant and anti-tremor effects. Among them, one can distinguish a new original biologically active substance habutamine - 1,3dichloro-2-chloromethylaminopropane hydrochloride, obtained at the Kazan Research Institute of Chemical Products. Based on the pharmacological effect of gabutamine, studied at the Department of Pharmacology of the KSMU, and the possibility of its use in all age groups, a rational dosage form was proposed - rectal suppositories.

&lt;i&gt;In vitro&lt;/i&gt; antiviral activity of VIFERON® rectal suppositories against SARS-CoV-2

In 2020–2021, the world was engulfed by the pandemic of a new coronavirus infection (COVID-19) caused by the SARS-CoV-2 virus. The low population coverage with vaccination against COVID-19 and the lack of herd immunity result in the need to find an effective and safe etiotropic treatment. Medicinal agents for treatment of COVID-19, approved while preparing this publication, have several limitations related to the conditions of their use and/or population category. In this situation, interferon-containing drugs widely used in Russia and the CIS for prevention and treatment of viral infectious diseases, i.e. ARVI and influenza, may hold promise. This study aims to confirm in vitro antiviral activity against SARS-CoV-2 for the preparation VIFERON® containing recombinant human interferon alpha-2b (IFNα-2b). Materials and methods. Vero CCL-81 cells were infected with hCoV-19/StPetersburg-RII3524VR4/2020 strain of SARS-CoV-2 at doses of 10 TCID50 or 100 TCID50 per well. The suppressive effect of IFN-2b, extracted from VIFERON® in dosage form of rectal suppositories, was evaluated by qRT-PCR at 24 h and 48 h after the infection of cells in two schemes, simulating preventive (24 h before infection) and therapeutic (2 h after infection) use of drugs. Results. IFNα-2b at concentrations of 800, 400, 200, 100 and 50 IU/ml, extracted from rectal suppositories of VIFERON®, showed high biological activity, displayed as inhibition of SARS-CoV-2 strain replication in both infectious doses evaluated either at 24 h or at 48 h after cell infection. The “preventive” vs. “therapeutic” scheme was found to be more effective. In the “preventive” scheme the virus titre decreased by more than 3 lg TCID50 at 24 hours post-infection and by 5–6 lg TCID50 at 48 hours post-infection after administration of 800 IU/ml IFNα-2b. Conclusion. The study results evidence that VIFERON® in dosage form of rectal suppositories may be promising for prevention and treatment of new coronavirus infection in clinical practice.

Efficacy of Diclofenac Transdermal Patch versus Diclofenac Rectal Suppository for Management of Postoperative Pain Following Open Cholecystectomy: A Randomised Clinical Trial

Introduction: Postoperative pain can have detrimental effects if proper analgesia is not provided. The most widely used medicines for the management of postoperative pain is Non Steroidal Anti-Inflammatory Drugs (NSAIDs), among the NSAIDs the most commonly used drug for postoperative pain is diclofenac sodium. Repeated intramuscular/intravenous (i.m/i.v.) injections of diclofenac are associated with pain and discomfort while oral use of diclofenac before and after surgery is limited and is also associated with increased risk of gastrointestinal complications like dyspepsia, peptic ulcer, etc. Diclofenac Transdermal Patch (TD) and Rectal Suppository (RS) are good methods of drug delivery as they avoid first pass metabolism, gastrointestinal complications and pain associated with i.m/i.v. route. Aim: To evaluate the efficacy of the transdermal diclofenac patch versus the diclofenac RS for management of postoperative pain. Materials and Methods: This hospital-based, randomised, prospective, interventional, open label comparative clinical trial was conducted in Department of General Surgery and Department of Pharmacology at FH Medical College and Hospital, Agra, Uttar Pradesh, India, from April 2021 to September 2021. A total of 64 patients were included in the trial and they were randomly divided into two groups using simple randomisation technique. Group A received 100mg diclofenac TD (n=32) and group B received 100 mg diclofenac RS (n=32) just before induction of anaesthesia and repeated 12 hourly for 48 hours. Pain was assessed postoperatively at 6, 12, 24 hours, respectively using the Visual Analogue Scale (VAS) and adverse effects like gastrointestinal complications were also noted in the both groups. The student's t-test was applied to compare the mean values of quantitative variables while qualitative variables were analysed using Chi-square test. p-value &lt;0.05 was considered statistically significant. Results: Both the groups were comparable with respect to age (p-value=0.1048) and gender distribution (p-value=0.3760). VAS score at 12 hours and 24 hours postsurgery in patients of both groups showed significant decrease (p-value &lt;0.001), when compared with VAS score values at 6 hours postsurgery of the same group. On comparison of VAS score between the two groups at 6 hour, 12 hour and 24 hour significant decrease (p-value &lt;0.05) in VAS score was observed with a higher decrement in group B patients i.e., those who received diclofenac rectal suppositories. In group A, seven patients needed rescue analgesia while in group B only three patients required rescue analgesia. Conclusion: Rectal diclofenac suppository had higher efficacy in comparison to transdermal diclofenac patch in management of postoperative pain.