Biopharmaceutical Trials of a Dosage Form, which Contain Methionine and Turmeric Extract (Curcuma longa L.)

Introduction. The presence of biologically active substances in the extract from the roots of turmeric extract (Curcuma longa L.) makes it reasonable and makes it possible to predict their effectiveness in pathological conditions caused by oxidative stress and immune disorders arising against its background. Based on data obtained, a pattern was revealed in improving the solubility of the combination of methionine and turmeric extract, which includes auxiliary substances. Dosage form – granules with methionine and liquid turmeric extract, with enteric coat can be used to eliminate the consequences of oxidative and immune disorders, treatment and prevention of systemic diseases caused by oxidative stress.Aim. Biopharmaceutical and in-process tests of the pharmaceutical composition of granules with methionine and liquid turmeric extract.Materials and methods. The object of the trials was the multicomponent drug containing methionine and a liquid turmeric extract of the roots. The proposed composition of plant compositions is original, had no analogues and protected by a patent for an invention (RU 268 4111). To assess the pharmaceutical properties, biopharmaceutical trials carried out by the UV-spectrophotometric method using biorelevant medium. The research results statistically processed using Statistica for Windows, version 10.Results and discussion. Based on the data obtained, a pattern revealed in improving the solubility of the combination of methionine and turmeric extract, in contrast to the multicomponent composition containing only turmeric extract.Conclusion. The developed multicomponent pharmaceutical composition will expand the register of herbal medicines of domestic production for the prevention and treatment of diseases caused by oxidative stress.

Bispecific anti-OX40/5T4 antibodies for cancer treatment

OX40 and 5T4 are molecules that play a role in T-cell expansion and cytoskeleton’s disruption in cancer, respectively. US2019161555 patent describes a bispecific antibody that targets OX40/5T4 with the potential application of cancer treatment. The method of analysis of the US201916155 patent consisted of claim’s analysis, as well as the chemical/biological information’s analysis of the bispecific antibody. The patent includes independent claims related to bispecific antibodies that bind to OX40/5T4, DNA encoding the antibodies, a vector that harbors the DNA, a host cell that contains the vector, a pharmaceutical composition containing a pharmaceutically effective amount of the antibodies, medical use of the antibodies, use of the antibodies in the treatment or prevention of neoplastic disorders and a method of treating neoplastic disorders. Bispecific antibodies that target OX40/5T4 can activate IL-2 secretion in CD4+ T cells.

Possibilities of in silico estimations for the development of pharmaceutical composition phytoladaptogene cytotoxic for bladder cancer cells

Based on the prediction of biological activity spectra for several secondary metabolites of medicinal plants using the PASS computer program and validation in vitro of the predictions results the priority direction of the pharmaceutical composition Phytoladaptogene (PLA) development was determined. PLA is a complex of structurally diverse small organic compounds including biologically active substances of phytoadaptogenes (ginsenosides from Panax ginseng, rhodionin from Rhodiola rosea and others) compiled considering previously developed pharmaceutical compositions. Two variants of the pharmaceutical composition were studied: — the major and minor variants included 22 and 13 compounds, respectively. The probability of activity exceeds the probability of inactivity for 1400 out of 1945 pharmacological effects and mechanisms predicted by PASS for the major variant of PLA. The wide range of predicted activities is mainly due to the low structural similarity of constituent compounds. An in silico prediction indicates the possibilities of antitumor properties against bladder, stomach, colon, ovarian and cervical cancers both for minor and major PLA compositions. It was found that the highest probability values of activity were predicted for three mechanisms: apoptosis agonist, caspase-3 stimulant, and transcription factor NF-κB inhibitor. According to the PharmaExpert program they are associated with the antitumor effect against bladder cancer. Experimental validation was using the human bladder cancer cell line RT-112. The results of the MTT test have shown that the cytotoxicity of the major PLA variant is higher than that of the minor PLA variant. In vitro experiments performed using two methods (double staining with annexin V and propidium iodide and detection of active caspase-3 in cells) confirmed that the death of bladder cancer cells occurred via the apoptotic mechanism. The data obtained correspond to the results of the prediction and indicate advantages of the major PLA composition. Thus, PLA can become the basis for the development of a drug with the antitumor activity against bladder cancer. The antitumor activity predicted by PASS for other cancers may be the subject of further studies.

Nutritional supplement for indigenous intestinal microflora: manufacturing, quality and effectiveness evaluation

The pharmaceutical composition of a nutritional supplement, which has a profound effect on the maintenance and development of the indigenous intestinal microflora, has been scientifically proven. The nutritional supplement is obtained by combining the encapsulation technology with the pellet technology to ensure that the pharmaceutical composition remains intact and the product appeals to consumers. The combination of encapsulation and pellet technology is highly beneficial to the manufacturing process as the delivery of the ingredients, which are very different in absorption and penetration rates, is improved, controlled and becomes very site-specific, while at the same time offering even distribution. The quality of the nutritional supplement has been proven and the product complies with the compulsory sanitary-hygienic and sanitarytoxicological regulations for dietary supplements. Clinical trials for the new nutritional supplement were performed to ensure the safety and the effectiveness of the product. Sixty volunteers aged from 33 to 72 were involved in the clinical trials. All of the volunteers were diagnosed with different intestinal microbiota disorders, among them a decreased number of microbial symbionts (bifidobacteria, lactobacilli, Escherichia coli (Lac +), the presence of Klebsiella pnenmoniae and opportunistic pathogens like Candida alticans. Patients with intestinal microbiota disorders were prescribed to take 1 capsule of the nutritional supplement twice a day for a period of 30 days together with other medicine prescribed to improve the biocenosis. Having taken part in the clinical trials, nearly 90% of patients, who had previously experienced such symptoms as bloating, gas, different abdominal pains, cramping, diarrhoea and constipation, demonstrated microbiota restoration, along with the overall health improvement. Considering the findings of the clinical trials, it should be noted that the use of ‘Panbiom’ nutritional supplement can play an important role in keeping the immune system healthy, with short chain fatty acids becoming the main focus of attention. Short chain fatty acids are the key to stimulating the immune response, as they support the regulatory T cells, prevent pathological changes and lessen the symptoms. The nutritional supplement composition and the manufacturing process were developed and tested at the scientific research-to-production facilities of Art-Life Scientific Production Association in Tomsk. All the mandatory documentation was obtained and fully complies with the requirements for nutritional supplements.

EXPERIMENTAL MODELS OF FETOPLACEENTAL INSUFFICIENCY IN ANIMALS (LITERATURE REVIEW AND OWN OBSERVATIONS)

This literature review is devoted to experimental models of placental disorders in animals. Today, our knowledge of the structure and function of the placenta during pregnancy is remaining limited. The use of new technologies and imaging methods in animals that can provide safe monitoring of the growth and function of the placenta in vivo requires preclinical studies and trials in appropriately developed animal models that can be easily translated into a clinical setting. All this, of course, requires the use of test animals for modelling placental pathologies. The review considers the positive and negative aspects of various animals and methods of modelling the pathological conditions during pregnancy. In the experiment, models of fetoplacental insufficiency are very often used, arising from oxidative stress and activation of free radical oxidation. To simulate the experimental fetoplacental insufficiency caused by histotoxic hypoxia, the xenobiotic tetrachloromethane is used. Women of very young and mature reproductive age have a high risk of fetoplacental insufficiency. It is not known exactly how placental insufficiency in mothers will affect the sexual development of pubertal offspring. That is why we conducted a comprehensive experimental study on this issue at the base of V. Danilevsky Institute of Endocrine Pathology Problems, NAMS of Ukraine. To solve this problem, our institute has developed and proposed a new pharmaceutical composition that should not only contribute to the correction of placental insufficiency, but also has a certain prophylactic value for maintaining reproductive potential in adulthood. The study was carried out on Wistar rats of two age groups. We modelled experimental fetoplacental insufficiency and then corrected it with this pharmaceutical composition. Our study made it possible to establish that fetoplacental insufficiency has a different effect on the formation of the reproductive system in male and female rats in puberty. Prophylactic adding of the composition to the food for pregnant female rats with modelled placental insufficiency leads to the decrease in reproductive diseases of their offspring in puberty. Research on animal models provides important insight into the molecular and functional mechanisms underlying fetoplacental insufficiency and intrauterine growth retardation, as it enables to carry out studies, which are not possible in pregnant women.

Development of technical regulations for the capsulated probiotic manufacture

The aim of this work was to develop a technological regulation for the production of probiotic based on lacto- and bifidobacteria in the form of intestinal-soluble capsules for farm animals. Three experimental series of probiotic drug were made in the form of enteric capsules based on lactic acid bacteria. It has been established that the Bifidobacterium adolectentis No 17-316 strain and the Lactobacillus plantarum No 7-317 strain are the most adapted for the bacterial consortium. These strains have high biological activity and correspond to certain authentic characteristics. The pharmaceutical composition is proposed in the form of capsules with following ingredients: 50% of dry biomass of Lactobacillus plantarum No 7-317 and Bifidobacterium adolectentis No 17-316 strains, 5% of glucose, 5% of lactose, 9% of aerosil and 31% of starch. The content of lyophilized bacteria in one capsule is not less than 1 × 107 CFU of bifidobacteria/cm3 and 1 × 107 CFU of lactobacilli/cm3. A scheme of the manufacturing process of the drug in form of capsules includes the following stages: production of nutrient media and working solutions; growing cultures of lacto- and bifidobacteria, freeze drying of cultures of lacto- and bifidobacteria, obtaining a dry mass of lactic acid bacteria for encapsulation, encapsulation of the drug, control of the manufactured product before release, marking, packaging of capsules, transportation, storage of a drug.

Biochemical Confirmation of the Anti-Inflammatory Effect of Coxibs and their Compositions with N-Acetylgulcosaminil 1-4-N-Acetylmuramoil-L-alanyl-D- Isoglagamin

The current work is focused on the biochemical confirmation of the anti-inflammatory effect of coxibs and their compositions with licopid as an adjuvant for NSAIDs in the treatment of inflammation. The current investigation aimed to compare the anti-inflammatory effect of rofecoxib, celecoxib, licopid, and pharmaceutical compositions consisting of rofecoxib and licopid, celecoxib, and licopid. Sodium diclofenac was chosen as the reference drug. The anti-inflammatory effect of the test substances was studied using an experimental model of formalin-induced paw edema. The level of SA was determined using SialoTest (SPC Eco-Service). A biochemical study of the anti-inflammatory effect of rofecoxib, celecoxib, licopid, and their composition on the content of inflammation marker (SA) showed that almost all studied drugs reduced the content of SA in rat’s blood serum compared to the negative control. The results of the biochemical study showed that rofecoxib has a pronounced anti-inflammatory effect. It acts almost 1.2 times better than celecoxib, and the leader in our biochemical studies is a two-component pharmaceutical composition of celecoxib + licopid at the level of SA in blood serum under formalin-induced edema.

Morphofunctional changes in testes of rats born to mothers with simulated fetoplacental insufficiency and its correction

Nowadays, it is almost unknown how fetoplacental insufficiency of mothers affects the formation of the reproductive system in male offspring during puberty. Therefore, the aim of this work was to study the histological structure of the testes of male offspring born to mothers of different ages with fetoplacental insufficiency and to evaluate the effectiveness of a new pharmaceutical composition for the correction of pathological conditions of pregnancy. The experiment involved healthy mature female Wistar rats in young (3–4 months) and mature (8–10 months) reproductive age. Eight groups with 7 pregnant females in each one were formed: groups 1 and 2 — intact animals of young and mature reproductive age, respectively; groups 3 and 4 — females with experimental fetoplacental insufficiency of young and mature reproductive age; groups 5 and 6 — young and mature animals with experimental fetoplacental insufficiency and addition to food depending on the weight of animals from 11 to 19 days of pregnancy pharmaceutical composition. Groups 7 and 8 — young and mature animals with experimental fetoplacental insufficiency with addition a comparison drug Dipyridamole to the food. Modeling of fetoplacental insufficiency was performed by daily subcutaneous injection to females from the 12th to the 18th day of pregnancy 50% oil solution of carbon tetrachloride at a dose of 2 ml/kg body weight. Offspring were decontaminated on the 50th day of life (puberty) by rapid decapitation. Samples of male testicles were fixed in 10% formalin solution, performed on alcohols of increasing strength, poured into paraffin. Sections were made from the blocks, which were stained with hematoxylin and eosin. Qualitative assessment of histostructure was performed on sections of the body in rats. Summing up the results of histological analysis and morphometric parameters characterizing the condition of the testicles of rats, we can draw the following conclusions. In the offspring born to reproductively young females with fetoplacental insufficiency, inhibition of the rate of germ cell differentiation was found, while in the offspring born to reproductively mature females with fetoplacental insufficiency, the negative effects of this effect were leveled and the rate of spermatogenesis increased. When the pharmaceutical composition was administered to both young and mature pregnant females on the background of fetoplacental insufficiency, it activated the processes of proliferation and differentiation of spermatogenic epithelium in their offspring, which was reflected in the appearance of mature sperm in the seminal tubules. The comparison drug Dipyridamole, administered according to the same regimen to both young and mature pregnant females with fetoplacental insufficiency, also helped the 50-day-old offspring of these females to restore the rate of spermatogenesis at the level of the pharmaceutical composition.