The aim of the work is analysis of the current state and trends in the metformin-based drug development with the subsequent formation of the logistics system of scientific research. Materials and methods. Studies were conducted using databases on the Internet (2015-2022): PubMed; U.S. Food and Drug Administration, European Medicines Agency, the State Expert Center of the Ministry of Health of Ukraine, scientific and metric databases - Scopus, Cochrane Database, US Patent Office. It has used retrospective, logical, graphic research methods, content analysis, modelling. Results. The model of the logistic system of metformin scientific research has developed. It represents the set of elements that are interconnected through information communication, its composition and features, which are associated with the pharmacological action of metformin, are determined. Logistic system of metformin scientific research allows: to demonstrate the uniqueness of the drug, to reveal its potential and new opportunities for medical use, prospects for the development of new types of dosage forms and new combined drugs; to identify the threat of patent infringement, to identify opportunities for establishing partnerships; to present scientific products in the form of a drug on the pharmaceutical market, optimizing the research time, reducing the development stages due to the available information and documentation, ensuring the synchronization of innovative information flows; to optimize the total costs of scientific research and receive at the expense of the specified profit. Logistic system of metformin scientific research is recommended for implementation in scientific organizations and pharmaceutical companies that perform R&D to achieve concentration of information search in solving logistics problems in the field of creating medicines based on metformin. Conclusions. Thus, the management of scientific research in pharmacy using the logistic approach ensures the time reduction of the medicine to entry into the market, reduces the cost of its creation, prevents duplication of research, and promotes optimization of solutions. The analysis revealed that the creation of medicines based on metformin should be aimed at the search and development of combined sugar-reducing drugs with mutually complementary mechanisms of action

The purpose of the study was to examine the levels of transforming growth factor-β1 in the serum of patients with coronary heart disease in combination with type 2 diabetes and without it. Material and methods. We conducted a survey of 65 patients (25 men, 40 women) aged from 36 to 69 years (mean age was (59±3.5) years). All patients were diagnosed with coronary heart disease in the form of stable angina pectoris I-II functional classes. The group of examined patients included 33 patients with concomitant type 2 diabetes mellitus (mild form was in 15 people; moderate was in 18 people) and 32 patients without diabetes mellitus. The scope of the survey covered the generally accepted methods of clinical, laboratory and instrumental examination. The group of patients with coronary heart disease with type 2 diabetes had 14 (43%) men and 19 (57%) women (mean age was (62±2.6) years. Heart failure of stage I-II A (I-II functional classes) was diagnosed in 22 (68%) patients. The duration of coronary heart disease was from 3 to 15 years, the duration of type 2 diabetes lasted from 3 to 14. We detected hypertension in 19 (57%) patients, it was within 1-2 degrees (according to the criteria of the Ukrainian Association of Cardiologists, 2008). In the group of patients with coronary heart disease without diabetes there were 11 men (34%), 21 women (66%) (mean age was (57.0±2.4) years). Hypertension within 1-2 degrees was detected in 15 (46%) patients. Heart failure of I-II A stages (I-II functional classes) was diagnosed in 15 (46%) patients. The control group consisted of 15 practically healthy individuals who were representative by sex and age of patients from the study group and who did not have diseases of the cardiovascular system and endocrinopathies. The level of transforming growth factor-β1 in the blood serum was determined using sets of standard test systems "TGF-β1 ELISA" produced by company "DRG Instruments" (Germany). The level of native transforming growth factor-β1 in the serum was determined by solid-phase enzyme-linked immunosorbent assay. Results and discussion. Groups of patients with coronary heart disease with type 2 diabetes and without it could be compared by age, sex, duration and severity of coronary heart disease, the frequency of concomitant hypertension. At the same time, among patients with coronary heart disease with type 2 diabetes there was a higher frequency of heart failure. The results showed that probable increase in serum transforming growth factor-β1 levels in patients with coronary heart disease was more pronounced when combining coronary heart disease with type 2 diabetes. There was a significant increase in serum of transforming growth factor -β1 levels in patients with coronary heart disease both with type 2 diabetes and without it with a longer course of coronary heart disease and were severer, in patients with coronary heart disease with type 2 diabetes was with a longer course of diabetes. Analysis of the nature of changes in the levels of transforming growth factor-β1 in the serum of the examined patients with coronary heart disease with type 2 diabetes and without it, depending on gender, did not reveal any significant differences. The results of the study also indicated that in patients with coronary heart disease with type 2 diabetes and without it for all duration of coronary heart disease, the levels of this indicator in the serum were probably (p <0.05) higher than those in the control group. However, in patients with a significant duration of coronary heart disease (5-10 years and over 10 years) serum levels of transforming growth factor-β1 were probably (p <0.05) higher than in patients with a duration of coronary heart disease less than 5 years, and in the presence of and in the absence of type 2 diabetes. At the same time, for all periods of coronary heart disease, the levels of transforming growth factor-β1 in patients with type 2 diabetes were probably higher than in patients without diabetes. Conclusion. A probable increase in the levels of transforming growth factor -β1 in the serum of patients with coronary heart disease, which was more pronounced when combining coronary heart disease with type 2 diabetes. There was a significant increase in the levels of transforming growth factor-β1 in the serum of patients with coronary heart disease both with type 2 diabetes and without it with a longer course of coronary heart disease and its severe degree, in patients with coronary heart disease with type 2 diabetes especially with a longer course of diabetes. In order to increase the informativeness of assessing the risk of cardiovascular complications and the nature of coronary heart disease in patients with type 2 diabetes, the survey should include determination of serum levels of potent profibrogenic factor like transforming growth factor-β1

The article considers the issue of disorders of connective tissue metabolism in diabetes mellitus. Glycosylation of structural components of connective tissue and glucose toxicity have been found to determine the pathogenesis of late complications of diabetes mellitus. The most common concept of the pathogenesis of diabetes is metabolic, according to which all variants of diabetes mellitus, including blood vessels, their basement membrane, are associated with primary disorders of lipid, glycoprotein, protein and carbohydrate metabolism due to complete or partial insufficiency. It has been found that the formation of interstitial fibrosis in the kidneys of patients with diabetes begins in the preclinical stages of diabetic nephropathy. The leading cause of interstitial fibrogenesis is hyperglycemia; exacerbate proteinuria fibrosis, activation of the renin-angiotensin system, chronic inflammation and the formation of myofibroblasts in the interstitium. According to the results of the study of aspects of early diagnosis of kidney damage in type 1 diabetes mellitus, it was found that the development of diabetic nephrosclerosis is characterized by qualitative and quantitative changes in collagen composition in the glomeruli and interstitium, rebalance between collagen synthesis and breakdown, glycosaminoglycans, increased synthesis of fibrogenic growth factors and oxidative modification of proteins. The formation of diabetic nephropathy in patients with diabetes is also characterized by the accumulation of collagen types IV and VI, the appearance of interstitial collagen types III and I in the glomeruli, as well as the accumulation of collagen of all types in tubulointerstitium. Quantitative and qualitative characteristics of sulfated glycosaminoglycans of urine in human diabetes indicated different degrees of development of diabetic nephropathy. Glycosaminoglycans hyperexcretion was observed in patients with diabetes mellitus without proteinuria. In patients with microalbuminuria, glycosaminoglycans hyperexcretion was even more pronounced. It was also found that in diabetes, the total excretion of sulfated glycosaminoglycans in the urine doubles. Conclusion. Thus, in diabetes mellitus, an important pathogenetic link in the violation of the morpho-functional state of the kidneys is the degradation of collagen and proteoglycans of the basement membranes of the glomeruli, as well as interstitial fibrosis. This is reflected in changes in urinary glycosaminoglycans excretion, in particular heparansulfate and chondroitin sulfate, which may serve as a marker of proteoglycan metabolism disorders in the kidneys. Patients with diabetes also have an increase in the urine of hydroxyproline, which indicates an increase in the intensity of collagen metabolism in patients

The aim of the work was to study the relationship between levels of vitamin D, obesity and lipid profilein patients with polycystic ovary syndrome (PCOS).Materials and methods. The study involved 120 women: 60 patients with PCOS and 60 healthy women.All examined were divided into groups depending on body mass index (BMI): patients with PCOS — 30 withBMI ≤ 25 kg/m2and 30 with BMI ≥ 25 kg/m2; healthy women — 30 with BMI ≤ 25 kg/m2and 30 withBMI ≥ 25 kg/m2. Results. Patients with a BMI of ≥ 25 kg/m2had a lower average level of vitamin D (P < 0,001) than patientswith a BMI of ≤ 25 kg/m2; among of them there was a higher percentage of women with a pronounceddeficiency (23.3% versus 13.3%) and deficiency (60% versus 50%) of vitamin D; nobody had not adequate levelsof vitamin D. It was established a negative correlation between the level of vitamin D and BMI (r = – 0.275;P < 0.05), waist circumference (r = – 0.604; P < 0.001), the coefficient of waist circumference/ hips circumference(r = – 0.512; P < 0.001). Abdominal type of adipose tissue distribution, which was observed among patients withboth overweight and normal weight, may be one of the factors contributing to dysregulation of metabolism of vitaminD in conditions of PCOS.Women with PCOS had lipid metabolism disorders with increased atherogenic and decreased levels of antiatherogeniclipid fractions wich was intensif with increasing body weight. It was established a negative correlationbetween the level of vitamin D and triglycerides (r = – 0.437; P < 0.001), and positive association with highdensity lipoprotein cholesterol (r = 0.492; P < 0.001).In healthy women, only a negative correlation between the concentration of vitamin D and BMI (r = – 0.562;P < 0.001) was establish and there was no association with other anthropometric indicators and indicators of theblood lipid spectrum.Conclusion. Patients with PCOS have a higher prevalence and severity of deficiency of vitamin D.Disruption of regulation of vitamin D metabolism may be a consequence of existing obesity, and a decrease invitamin D levels is an additional factor that increase the dyslipidemia that exists in PCOS.

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