Suppository Formulations Research Articles

Effect of Selected Surfactants on Kinetics of Meloxicam Release from Rectal Suppositories

The use of surfactants in suppository formulations has been suggested to improve the bioavailability of poorly soluble drugs. In the present study, different kinds of surfactants were investigated to understand their influence on meloxicam release from suppositories formulated with a lipophilic base. Tween 80, Span 80, soy lecithin and sodium lauryl sulfate were the surfactants used in this study. The suppositories were prepared in a recipe mixer using Witepsol H15 and cacao oleum as a base. The suppositories with and without the addition of surfactants were examined using physicochemical tests according to the Polish Pharmacopeia, the uniformity of mass of single-dose preparation test, the content uniformity test, the softening time determination of lipophilic suppositories test, the disintegration test of suppositories, and the dissolution test. All the prepared formulations complied with the pharmacopeia requirements. The prepared suppositories were evaluated for in vitro drug release immediately after preparation and after storage. The results revealed that the bioavailability of meloxicam was to 36 % from suppositories formulated with Witepsol H15 and 23.4 % those formulated with cacao oleum. Addition of surfactants to the suppository base significantly influenced both the amount and rate of meloxicam released into the phosphate buffer. The highest release rate of meloxicam was observed with the formulation prepared on a Witepsol H15 base with Tween 80. Present results have confirmed the possibility of using surfactants in suppository formulations, in order to improve the dissolution rate of meloxicam in vitro. As a consequence, a faster onset of pharmacodynamic action and better therapeutic effects of the medication can be obtained.

Formulation and evaluation of acetylsalicylic acid suppositories using capra hircus (goat) fat and its binary blends

Formulation and evaluation of acetylsalicylic acid suppositories using capra hircus (goat) fat and its binary blends

Povidon-iodine (betadine) in modern obstetric-gynecological practice

The article describes the pharmacocodynamics of povidone-iodine, the release form under the brand name Betadine, pharmacological benefits, as well as evidence of its effectiveness in preventing infection in the field of surgical intervention. Povidone-iodine is indicated to be a depot of iodine, constantly releasing elemental iodine, which has strong oxidizing properties, and therefore most microorganisms are destroyed in vitro in less than a minute, and the main destructive effect of the drug occurs in the first 15–30 seconds. Povidone-iodine has a wide spectrum of antimicrobial and antiviral action. The data on medications of povidone-iodine in the form of vaginal suppositories, antiseptic solution and ointment under the trade name Betadine are presented. Own data on the effective use of vaginal suppositories in symptomatic vaginal dysbiosis caused by mixed opportunistic bacterial flora (facultative and obligate anaerobes) with the presence of Atopobium vaginae in diagnostically significant amounts are presented. In the presented comparative studies, the advantages of Betadine compared with other antiseptics in the spectrum of microbiological effects, resistance of microorganisms, effects on wound healing, dependence of the effect on the physico-chemical parameters of the environment, side effects, the purpose of application – prevention and/or treatment are shown. The results of recent comparative studies on the treatment of the surgical area with chlohexidine-alcohol and povidone-iodine, according to which povidone-iodine should still be considered acceptable for the preoperative treatment of the caesarean section, are highlighted. It is indicated that the irrigation of the wound cavity with an aqueous solution of povidone-iodine during surgery and before suturing the surgical wound is one of the WHO recommendations for the prevention of infection in the field of surgical intervention. The authors conclude that povidone-iodine, including Betadine, has a broad spectrum of antimicrobial and antiviral activity; high activity in the presence of organic compounds (blood, pus); ability to penetrate through biofilms, necrotic tissue, eschar; low incidence of antiseptic resistance; positive dynamics of wound healing by preventing the spread of inflammation and increasing the ability to heal; well tolerated by patients; low cost; ease of use.

EFFECT OF POTENTIAL MEDICINAL PRODUCT ANTI-INFLAMMATORY AND ANTIMICROBIAL ACTIVITY ON THE FATTY-ACIDIC COMPOSITION OF THE VAGINE TISSUE AND BLOOD SERUM OF RATS WITH EXPERIMENTAL VAGINITIS

The purpose of the study was to investigate the effect of a potential combined drug with antimicrobial and antiinflammatory activity on the fatty acid composition of lipids in vaginal tissue and blood serum of rats with simulated vaginitis.
 Materials and methods. The study was conducted on 35 female rats of the Vistar line weighing 180-220 g. Animals were divided into 5 groups: 1 – intact animals, control; 2 –animals with simulated traumatic vaginitis (TV); 3 – TV + base for suppository; 4 – TV + study drug with antiinflammatory and antimicrobial activity in the form of vaginal suppository; 5 – TV + comparative product Neo-Penotran® (“Ekselstix Helske SL”, Spain) in the form of a vaginal suppository. The study drug contained ibuprofen, clotrimazole and metronidazole in the form of suppositories. Composition Neo-Penotran® contains miconazole and metronidazole. Basis of the both medicines was the same – Vitepsol. Determination of the fatty acid composition of lipids in the tissues of the vagina and serum was carried out using the gas chromatography method.
 The results revealed 9 of the most informative fatty acids: of them meristic C14:0, pentodecan C15:0, palmitinic C16:0, stearic C18:0 related to saturated fatty acids (SFAs), and oleinic C18:1, linoleic C18:2, linolenic C18:3, arachidonic C20:4, which is the sum of unsaturated fatty acids (UFAs). Linoleic C18:2, linolenic C18:3, arachidone C20:4 LC are part of polyunsaturated fatty acids (PUFAs) and are characterized as essential.
 Conclusions. The study results showed that there is a change in the total content of SFA, UFA and PUFA in the background of traumatic vaginitis: SFAs – 44.5%, UFA – 55.5% and PUFA – 31.9% versus 50.4%, 49.6% and 27.5% of lipids in the vaginal tissue in the control group. It was found that after administration of the study drug against the background of traumatic vaginitis, the normalization of the SFA ratio was 37.8%, the UFA 62.2%, and the PUFA – 44.4% compared to 43.3%, 56.7% and 35.4% serum lipids in the control pathology.

Clinico-laboratory efficacy of the drug Viferon® in viral lesions of the gastroin-testinal tract in children

In recent years, viral lesions of the gastrointestinal tract take the leading place in the etiological structure of acute intestinal infections. The study of the clinical course and treatment of viral diarrhea in children is an urgent task in modern conditions. We analyzed the disease of 2568 children aged 1 month to 17 years who were hospitalized in a Hospital No 3 in St. Petersburg in the period of 2016-2017. All patients underwent a standard laboratory examination. The etiological interpretation was carried out with the help of polymerase chain reaction, bacteriological and serological methods of investigation. Of the 2568 children in 1502 (58.5%) patients, the diagnosis was confirmed. The share of bacterial diarrhea was 31.8%, viral lesions of the gastrointestinal tract – 68.2%. Among the decoded viral lesions of the gastrointestinal tract, the share of rotavirus infection was 52.8%, norovirus infection – 24.8%, mixed infection – 19.6%. A high proportion of viral lesions of the gastrointestinal tract was established in children under 3 years of age (71.7%). The main reason for hospitalization of children under 5 years of age is rotavirus infection, from 5 to 12 years – norovirus infection. Almost always (87.6%), viral diarrhea proceeded in a moderate form. In infants, mixed viral infection was recorded in severe form. The use of Viferon® in the form of rectal suppositories to supplement the basic therapy of viral intestinal infections significantly reduces the duration of intoxication syndrome, fever, diarrhea, catarrhal syndrome, the duration elimination of viruses, and the length of stay in the hospital.

Physico-chemical and pharmaco-technological research at a substantiation of rational composition and technology of suppositories «indoxam»

The development of new highly effective drugs in the form of rectal suppositories for the treatment of diseases of the prostate gland does not lose its relevance today, since the number of patients with these pathologies is increasing every year. These diseases adversely affect the physical, psychological health and quality of life of men in general. An important issue in the substantiation of the composition and development of the technology for the production of suppositories is the study of their physico-chemical and pharmaco-technological properties that directly affect their consumer qualities and the mode of the technological process. Aim of the work was the study of the physico-chemical and pharmaco-technological properties of the combined rectal suppositories Indoxam to select rational conditions of the technological process. Materials and methods . In order to substantiate the composition and technology of the combined rectal suppositories “Indoxam”, modern physicochemical (thermal analysis, rotational viscometry method) and pharmaco-technological (disintegration suppositories, resistance to degradation) studies were used according to the requirements of SPHU. Results. To select the optimal ratio of polyethylene oxides in the suppository base, the resistance of suppositories to destruction and the disintegration time of samples made with different amounts of PEO-1500 and PEO-400 were studied. To determine the optimal technology for the preparation of the drug, a study was made of the decomposition temperature of the API, which makes it possible to determine the temperature regimes for the preparation of suppositories and the introduction of active substances into the base without the risk of destroying the structure of substances and changing their pharmacological actions. Since, under the influence of mechanical, thermal, and other actions, several types of destruction undergo suppositories, their rheological characteristics are also investigated. Conclusions . The results of pharmaco-technological research allowed to substantiate the optimal ratio of polyethylene oxides in suppository basis. The conducted thermogravimetric analysis of API and suppositories «Indoxam» established the thermal stability of substances and the absence of chemical interaction between the components in the composition of rectal drug. According to the rheological characteristics, the system identified the thixotropy and the optimal pouring temperature of the suppository mass

Обоснование назначения и эффективность препарата Лонгидаза у больных хроническим простатитом

Chronic inflammation of the prostate leads to the formation of excess fibrous connective tissue, which hinders patients recovery and aggravates the symptoms. This study aimed to confirm the correlation between inflammation and prostatic fibrosis and the abnormalities of urodynamic and microcirculation in the prostate gland in humans, and the possibility of increasing the effectiveness of treatment of patients with chronic nonbacterial prostatitis using antisclerotic therapy. The study was carried out in two stages. At the first stage, pathomorphological findings, uroflowmetry data and degree of microcirculation disturbance were studied in 18 patients with chronic prostatitis who underwent prostate biopsy. At the second stage, an open prospective randomized comparative study was conducted. Two groups of patients with chronic nonbacterial prostatitis with signs of inflammation were formed. A control group (n=29) received standard treatment, rectal 0.5 methyluracil suppositories three times per week, 20 suppositories per course. In addition to the standard treatment, the patients of the study group (n=31) were administered Longidaza 3000 IU rectal suppositories also three times a week, 20 suppositories per course. Prostatic fibrosis worsens microcirculation by one and half times and statistically significantly negatively affects urodynamic. Using Longidaza resulted in neutralizing the negative consequences of the formation of excess fibrous connective tissue. Overall, an excellent and good effect was achieved in 21 (67.7%) and 9 (29.1%) patients of the study group, respectively; only in one case (3.2%) there was no effect. In the control group, an excellent and good effect was achieved in 14 (48.3%) and 11 (37.9%) patients, respectively; in 4 patients (13.8%) the treatment was considered of low effectiveness. Prevention of the fibrous connective tissue formation and regression of the fibrosis are pathogenetically valid. Anti-sclerotic enzyme therapy with Longidaza in the form of rectal suppositories results in a significant improvement in the symptoms of prostatitis, an increase in the maximum urinary flow rate and an improvement in the microcirculation of the prostate.

Influence of the estrus cycle of the mouse on the disposition of SHetA2 after vaginal administration

SHetA2 is a novel compound with the potential to treat cervical dysplasia, but has poor water solubility. A vaginal suppository formulation was able to achieve therapeutic concentrations in the cervix of mice, but these concentrations were variable. Histological analysis indicated that mice in the same group were in different stages of their estrous cycle, which is known to induce anatomical changes in their gynecological tissues. We investigated the effects of these changes on the pharmacokinetics and pharmacodynamics of SHetA2 when administered vaginally. Mice were synchronized to be either in estrous or diestrus stage for administration of the SHetA2 suppository. Pharmacokinetic parameters were calculated from the SHetA2 concentrations vs. time data. The reduction in the expression of cyclin D1 protein in the cervix was used as pharmacodynamic endpoint. Mice dosed during diestrus had a larger AUCcervix (335 μg mL h−1), higher Cmax (121.8 ± 38.7 µg/g) and longer t1/2-cervix (30.3 h) compared to mice dosed during estrus (120 μg mL h−1, 44.6 ± 29.5 µg/g and 3.6 h respectively). Therapeutic concentrations of SHetA2 were maintained for 48 h in the cervix of mice dosed during diestrus and for only 12 h in the estrus group. The treatment reduced the expression of cyclin D1 protein in the cervix of mice in the estrus to a larger extent. These results indicate that the estrous cycle of mice influences significantly the disposition of SHetA2 after vaginal administration and may also influence its efficacy.

Improve Solubility of Acetamidophenol from PEG and Witepsol Suppositories via Formation of Inclusion Complex by β-Cyclodextrin with a Controlled Release Profile

Acetamidophenol (ACP) is used to treat mild to moderate pain and reduce fever, but low water solubility and poorly dissolution of this compound restricted its bioavailability. To overcome these problems and enhance the solubility of ACP, inclusion complex between ACP and β-cyclodextrin (β-CD) is formed with various mass ratios of β-CD:ACP (1:1, 1:2, 1:4, 1:8), and the effect of complex formation on solubility and release of ACP from PEG and Witepsol-based suppositories through rectal route of administration is investigated. Inclusion complexes formed with various ratios of β-CD:ACP and loaded in the formulation of suppositories by fusion method utilizing different suppository bases, i.e., Witepsol H15 and polyethylene glycol (4000, 400). FTIR, SEM, and XRD results indicate formation of inclusion complex between β-CD and ACP. Physical characteristics and in vitro drug release of the obtained suppositories are determined by several tests such as weight variation, melting point, hardness, and release rate. Results indicate that PEG-based suppositories containing β-CD:ACP 1:1 mass ratio show the best in vitro drug release characteristic which released 19.3% of ACP after 8 h.

Pharmacokinetics and Tolerability of Δ9-THC-Hemisuccinate in a Suppository Formulation as an Alternative to Capsules for the Systemic Delivery of Δ9-THC

The objectives of this study were: (1) to assess the safety, tolerability, and pharmacokinetics of ascending doses of Δ⁹-tetrahydrocannabinol-hemisuccinate (THC-HS) after rectal administration as suppositories in male volunteers; and (2) to compare the pharmacokinetics of oral administration of Δ⁹-tetrahydrocannabinol (Δ⁹-THC) with an equivalent amount of Δ⁹-THC delivered as THC-HS via the suppository formulation. In support of the pharmacokinetic evaluations, an analytical method was developed and validated for the determination of Δ⁹-THC and for its major circulating metabolites 11-hydroxy-Δ⁹-tetrahydrocannabinol (11-OH-THC) and 11-nor-Δ⁹-tetrahydrocannabinol-9-carboxylic acid (THC-COOH) in human plasma. Δ⁹-THC, 11-OH-THC, and THC-COOH were extracted from plasma using solid phase extraction and analyzed by liquid chromatography-tandem mass spectrometry. The limits of detection and quantitation for all 3 analytes were 0.25 and 0.5 ng/mL, respectively. The method was validated over the range of 0.5–25 ng/mL. This method was used to quantify Δ⁹-THC and any THC-HS as Δ⁹-THC due to the inclusion of a hydrolysis step as part of the extraction procedure. Therefore, Δ⁹-THC measured was the total THC (free Δ⁹-THC plus Δ⁹-THC derived from THC-HS). The assay was reproducible for the measurement of all 3 analytes, with a variability of 7.2, 13.7, and 8.3%, respectively, at the 1 ng/mL level. The method was then used to assess the pharmacokinetics of Δ⁹-THC and metabolites from the suppository dosage form in doses equivalent to 1.25, 2.5, 5, 10, and 20 mg Δ⁹-THC per suppository as THC-HS. Systemic exposure to Δ⁹-THC, administered as THC-HS suppository, increased broadly dose proportionally. Systemic exposure and C_{max (obs)} estimates for 11-OH-THC and THC-COOH generally increased subproportionally. The pharmacokinetic profiles of Δ⁹-THC and metabolites were also compared after oral administration of 10 mg Δ⁹-THC (as dronabinol capsules) and after administration of 10 mg equivalents of Δ⁹-THC as THC-HS in suppository form. Total systemic exposure to Δ⁹-THC was considerably higher following rectal administration of THC-HS than after oral administration. The Δ⁹-THC area under the plasma concentration versus time curve (AUC_(0–_∞₎) for THC-HS was 2.44-fold higher (90% confidence interval: 1.78, 3.35) than for the capsule administration.

The effect of a vaginal suppository formulation of dill (Anethum graveolens) in comparison to clotrimazole vaginal tablet on the treatment of vulvovaginal candidiasis

The goal of this study was to compare the effect of Anethum graveolens (dill) vaginal suppositories and 100 mg clotrimazole vaginal tablets on vulvovaginal Candidiasis. This study was a single centre, single-blind, randomised, placebo-controlled trial, in which 60 women with microbiology-confirmed vulvovaginal candidiasis were randomly assigned to dill and clotrimazole groups. At the end of the study, the estimated prevalence of leucorrhoea, burning, and itching was 23%, 23% and 20% in dill users, respectively. This figure was 20%, 10% and 16.7% for the clotrimazole group, respectively. The difference between the two groups was not significant. 13% of suppository patients, compared with 10% of clotrimazole-treatment patients, had a positive culture, which was not significant (p = .68). According to findings, 2% dill vaginal suppositories were as effective as clotrimazole vaginal tablets in reducing both clinical and microbiological symptoms of Candidiasis. Studies with larger sample sizes are required to confirm current findings.Impact statementWhat is already known on the subject? Based on results from in vivo and in vitro animal studies, dill (Anethum graveolens) has anti-candida activity.What do the results of this study add? It appears that 2% dill vaginal suppositories were as effective as 100 mg clotrimazole vaginal tablets in reducing both the clinical and microbiological symptoms.What are the implications of these findings for clinical practice and further research? Obstetricians and gynaecologists can offer dill as a useful alternative to chemical drugs, especially in women who are often interested in herbal medicine, or in women who are resistant or are not allowed to use antifungal drugs.

Use of Lactobacillus spp. to prevent recurrent urinary tract infections in females

Urinary tract infections (UTIs) are the most common bacterial infections seen in the community, especially amongst females. The widespread use of antibiotics has led to the increased occurrence of E. coli resistant isolates worldwide. A promising non-antibiotic approach is the use of probiotic lactobacilli strains. This paper hypothesizes that Lactobacillus spp. containing products are able to prevent recurrent urinary tract infections in females. Using the keywords [lactobacillus OR lactobacilli OR probiotic] and [urinary tract infection OR UTI OR cystitis], a preliminary search on the PubMed, Ovid, Google Scholar and ClinicalTrials.gov database yielded 1,647 papers published in English between 1-Jan-1960 and 1-May-2017. 9 clinical trials with a total of 726 patients were reviewed. Different lactobacilli strains (in either oral or suppository formulation) were utilized and they demonstrated varying efficacy in the prevention of recurrent UTIs. Using a random-effects model, pooled risk ratio of at least one recurrent UTI episode during the entire study duration was 0.684 (95% CI 0.438 to 0.929, p < 0.001), per-protocol analysis. However, key limitations include significant inter-study variability and the limited duration of follow-up of most studies. Our hypothesis on the chemoprophylactic effects of probiotics for UTIs is plausible and supported by current data. Lactobacillus rhamnosus GR1 and Lactobacillus reuteri RC14 were the most commonly studied lactobacilli strains. Further and more robust randomized controlled trials with standardized lactobacilli strains and formulation are required for confirmation of effects.

Rectal Suppository of Mucoadhesive Microspheres of Alverine Citrate for İrritable Bowel Disease: In vitro Evaluation

The aim of present investigation was to develop chitosan based mucoadhesive microspheres of alverine citrate (ALV) for rectal delivery. Mucoadhesive microspheres of alverine citrate were prepared by simple emulsification crosslinking technique and evaluated for surface morphology, particle size, equilibrium swelling degree, drug content, in vitro bioadhesion and in vitro drug release. The suppositories of optimized batch of microspheres (AM5) were prepared by fusion method using cocoa butter, polyethylene glycol (PEG) 2000, PEG 4000 alone or in combinations with different ratios and evaluated for weight variation, hardness, drug content uniformity, liquefaction time, micro-melting range, in vitrodissolution and compatibility study by Attenuated total reflectance- Fourier transform infrared spectroscopy (ATR-FTIR). Chitosan based mucoadhesive microspheres of all batches of ALV except AM3 and AM4 showed spherical shape and particle size in the range of 76.56 to 294.32µm. All the formulations showed drug encapsulation efficiency in the range of 43.91 to 98.36% and bioadhesion in the range of 58.25 to 82.65%. AM5 batch showed 94.65% drug release at the end of 10h. Formulations of solid suppositories showed all the physical parameters within prescribed pharmacopoeial standard limits. Drug content of all the batches of suppositories was found to be in the range of 70.94 to 91.65%. All the batches of suppositories retarded the release of drug at the end of 10h. Suppository batch E showed 86.33% drug release at the end of 10h. Developed rectal formulation of ALV could be able to relieve the symptoms of irritable bowel disease and may overcome the disadvantages of oral delivery.

Formulation and Evaluation of Chlortenoxicam Rectal Suppositories

Formulation and Evaluation of Chlortenoxicam Rectal Suppositories

Пути снижения диагностической и лечебной агрессии у пациенток с ВПЧ-инфекцией в репродуктивном возрасте

The problem of early diagnostics and prevention of cervical cancer is actual in Ukraine.The leading etiologic factor in the genesis of cervical neoplasia and a number of other organs is Human papillomavirus (HPV). The human papillomavirus is sexually transmitted and has high contagiosity. Cancer prevention consists in effective screening, early detection and treatment of pathological changes in the cervix. The aggressive treatment of diseases caused by (HPV) has been replaced by a tactic of a differentiated approach, taking into account to the age of the woman and her reproductive plans. The objective: was to study the efficacy and tolerability of the combined use of Proteflazid® systemically in drops form and locally in the form of suppositories for 3 months in patients with cervical intraepithelial neoplasia (CIN) of lung and moderate severity (CIN 1 and CIN 2) associated with the human papillomavirus (HPV); determination on the basis of the results of the need for further destructive treatment. Materials and methods. For the period from July 2016 to September 2017, we examined and treated 86 women with morphologically confirmed intraepithelial neoplasia of the cervix associated with HPV infection. Results. Based on the performed studies, it was found that 6 months after treatment with Proteplasid® systemically and locally for 3 months, regression of CIN was noted in 93% of patients. In all cases, a reduction in viral load of more than 2 Lg of HPV/105, which is a marker of the effectiveness of antiviral therapy, has been recorded. Six months after treatment in 84% of patients and 9 months in 88%, there was complete elimination of HPV or reduced viral load to clinically insignificant values – less than 3 Lg. Conclusion. The drug Proteflazid® suppositories and drops contributes to the elimination of human papillomavirus (HPV) and other viral-bacterial infections and reduces the risk of cervical neoplasia. Key words: cervical cancer, screening, cervical neoplasia, Human papillomavirus, viral-bacterial infections, Proteflazid®.

MICROBIOLOGICAL STUDIES OF ANTI-HISTAMINE SUPPOSITORIES "LORAVIT" FOR CHILDREN

Among the current problems of medicine and pharmacy, attracting the attention of researchers around the world, allergic diseases are on an important place; for example, bronchial asthma, allergic rhinitis, atopic dermatitis, and others. These pathologies affect their abundance not only among adults, but also among children [1]. According to statistics, almost every child had allergic reactions to drugs, food, clothing, hygiene products, etc. at least once [2]. In this regard, we have developed a new anti-allergic drug for children in the form of suppositories under the conditional name "Loravit". The purpose of this work was to conduct microbiological research of new anti-allergic drug "Loravit" for children in the rectal dosage form. During researches, the correlation of the growth properties of nutrients was analyzed and the microbiological purity of the drug "Loravit" was studied. A thioglyсol semi-liquid substratum, Saburo’s substratum, solid nutrient substrata: nutrient agar, Saburo’s substratum, Chistovich's substratum, nutrient agar based on blood agar, Endo’s substratum, and also test microorganisms - Staphylococcus aureus ATCC 6538, Esherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 9027, Bacillus subtilis ATCC 6633, Candida albicans ATCC 885/653 were used for carrying out these studies. In the study of microbiological purity, the method of direct seeding on liquid nutrient substrata and the method of deep sowing were applied. As a result of the conducted studies it was established that a new medicinal product for children in the form of suppositories for the treatment of allergic diseases meets the requirements of the State Pharmacopoeia of Ukraine and European Pharmacopeia for the indicator "Microbiological purity". The norms of microbiological purity of suppositories "Loravit" are also established. The test results were included in the draft quality control methods for the developed drug.

A formulation of pancreatic pro-enzymes provides potent anti-tumour efficacy: a pilot study focused on pancreatic and ovarian cancer

Proteolytic enzymes have shown efficacy in cancer therapy. We present a combination of the two pro-enzymes Trypsinogen and Chymotrypsinogen A with potent in vitro and in vivo anti-tumour efficacy. A synergetic anti-tumour effect for Trypsinogen and Chymotrypsinogen A was determined at a ratio 1:6 (named PRP) using 24 human cancer cell lines. The antiangiogenic effect of PRP was analysed by matrigel-based tube formation and by fibrous capsule formation assays. Furthermore, cell invasion and wound healing assays together with qRT-PCR determination of epithelial-to-mesenchymal transition (EMT) markers were performed on human cancer cells treated with PRP. Additionally, in vivo pharmacokinetic studies were implemented and the PRP’s anti-tumour efficacy was explored against orthotopic pancreatic and ovarian cancer tumours. PRP formulation was proven to inhibit in vitro angiogenesis, tumour growth, cancer cell migration and invasiveness; and to be an effective and well tolerated in vivo anti-tumour treatment. Finally, the clinical efficacy of a suppository formulation containing both pancreatic pro-enzymes in the context of a UK Pharmaceuticals Special Scheme was evaluated in advanced cancer patients. Consequently, PRP could have relevant oncological clinical applications for the treatment of advanced or metastatic pancreatic adenocarcinoma and advanced epithelial ovarian cancer.

Optimization of a Vaginal Suppository Formulation to Deliver SHetA2 as a Novel Treatment for Cervical Dysplasia

Cervical dysplasia induced by the human papilloma virus unpredictably progresses to cervical cancer. Therapeutic options are invasive and affect the patient's quality of life. SHetA2 has demonstrated therapeutic efficacy against human and murine human papilloma virus–induced tumors, but its oral bioavailability is <1%. An optimized vaginal suppository formulation can deliver SHetA2 in sufficient doses to prevent cervical dysplasia. The quality by design approach was employed to optimize the suppository formulation consisting of cocoa butter as base with 5% Kolliphor and 40% SHetA2. The suppository had a content uniformity of 105.44 ± 0.42%, melted in <8 min, and had a complete release of SHetA2 in water. Administration of the suppository to mice-achieved cervix concentrations that were significantly higher than the SHetA2 therapeutic concentration, with the maximum concentration (Cmax-cervix = 336.78 μg/g) being more than 100-fold the therapeutic SHetA2 concentration. Furthermore, the levels of cyclin D1 protein decreased 9-fold indicating a correlation of drug concentrations with the pharmacodynamic endpoint. These proof-of-concept studies suggest that the SHetA2 optimized vaginal suppository formulation may have a potential use in the prevention of cervical dysplasia, but detailed efficacy studies are required to confirm this assumption.

ОСОБЛИВОСТІ БІОЦЕНОЗУ ТА ФУНКЦІОНАЛЬНОЇ АКТИВНОСТІ ВАГІНАЛЬНОГО ЕПІТЕЛІЮ ПРИ МІСЦЕВОМУ ЛІКУВАННІ НЕСПЕЦИФІЧНОГО ВАГІНІТУ

Мета дослідження – оцінити клінічну та мікробіологічну ефективність і безпечність застосування препарату «Кломезол» у лікуванні неспецифічного вагініту.Матеріали та методи. Для вирішення поставленого завдання проведено обстеження і лікування 60 жінок репродуктивного віку з діагнозом аеробного вагініту. Проведено оцінку клінічної та мікробіологічної ефективності терапії у пацієнток з аеробним вагінітом. Вивчено терміни зникнення об’єктивних і суб’єктивних симптомів запального процесу, особливості функціональної активності епітелію піхви, вплив препарату на стан нормальної мікрофлори піхви. Дослідження проведено відповідно до міжнародних нормативів і правил GCP.Результати дослідження та їх обговорення. У результаті проведеного дослідження було встановлено, що комбінований препарат «Кломезол» у вигляді вагінальних свічок є ефективним по відношенню до умовно-патогенних мікроорганізмів – збудників аеробного вагініту і є препаратом вибору для лікування бактеріального вагінозу та аеробного вагініту. Кломезол не здійснює імуносупресивного впливу на епітелій піхви, завдяки цьому відновлення функціональної активності епітелію після лікування кломезолом відбувається швидше, ніж після лікування тержинаном. Відмічено покращення якості життя пацієнток після лікування.Висновки. Відмічена висока ефективність комбінованого препарату «Кломезол» по відношенню до широкого спектра мікрофлори, доведена висока терапевтична активність та безпечність у використанні у пацієнток з аеробними вагінітами. Кломезол добре переноситься та не викликає резистентності мікрофлори. Препарат може використовуватись у ІІ і ІІІ триместрах вагітності.

Важка дисплазія епітелію шийки матки та внутрішньоепітеліальна карцинома (ЦІН 3) з поширенням на склепіння та стінки піхви. Діагностика та лікування

The objective: to study and systematize the main clinical variants of CIN 3 with the spread of atypical epithelium to the vaults and walls of the vagina; to develop complex approaches to the treatment of patients with CIN 3 with the spread of atypical epithelium to the vaults and walls of the vagina with neoadjuvant therapy and surgical treatment; to study the therapeutic effectiveness of the use of a2b-interferon in the form of vaginal suppositories and Tyloron in the complex treatment of patients with CIN 3 with the spread of abnormal epithelium to the vaults and walls of the vagina during the first stage of complex drug treatment. Patients and methods. A survey of 62 patients with histologically verified CIN 3 with the spread of atypical epithelium to the vaults and walls of the vagina was carried out. At the stage of neoadjuvant etiotropic therapy, the patients were randomized into two groups. 31 patients were included in the main group (A), 31 patients were included in the control group (B). In group A, patients with neoadjuvant were given б2b-interferon at 500 000 IU in the form of vaginal suppositories twice a day for 14 days and a Tyloron 1 tablet 125 mg once a day in a day No.10. In group B, the standard therapy is intended for patients – an a2b-interferon of 500 000 IU in the form of vaginal suppositories twice a day for 14 days. The surgical stage of treatment was carried out in accordance with the clinical and histological diagnosis and the variant of the process spread to the walls of the vagina. Diathermoconization of the cervix and combined vaginal trachelectomy type A with resection of the upper third of the vagina were performed. Results. Three clinical variants of CIN 3 with spreading to the vaults and walls of the vagina were established. The first clinical variant – CIN 3 is localized to ectocervix, CIN 1–2 (IHC p16 negative) is localized on the vaults and walls of the vagina. The second clinical variant – CIN 3 is localized on ectocervix and extends to the vault and walls of the vagina. The third clinical variant – CIN 3 is localized on ectocervix and multicentric dissemination of CIN 3 – on vaults and walls of the vagina. The choice of an integrated treatment program with a surgical component depends on the clinical option. Conclusions. 1. Three clinical variants of CIN 3 with spreading to the vault and walls of the vagina have been established. Half the patients had the first clinical variant. 2. The main colposcopic signs of CIN 3 with spreading to the vaults and walls of the vagina: dense acetic-white epithelium, coarse mosaic, a sign of the internal border. 3. In 3 weeks after the course of treatment with neoadjuvant therapy in combination of Тyloron with a2b-interferon in the form of vaginal suppositories, it is possible to achieve from 85 to 100.0% positive dynamics, whereas in the traditional method of treatment, from 41 to 75%, which is statistically significant less (p&lt;0.01). 4. The study showed that there is a relatively strong statistically significant association of neoadjuvant therapy using a combination of Tyloron with interferon-a2b suppositories in the complex treatment of CIN3 with spreading to the vault and vaginal walls compared to conventional therapy (c21=10.64; j=0.41; p&lt;0.01). After three weeks, the positive dynamics in the main group (A) significantly increased (RR=1.6; 95% CI: 1.2–2.2; p&lt;0.01). Key words: CIN 3, vaginal vault, vagina, trachelectomy, treatment.