Vol 2, No 1 (2020)

From the editor

From the editors

Narkevich I.A.


From the editors

Pharmacy Formulas. 2020;2(1):1-1
pages 1-1 views

Pharmaceutical Sciences

Approaches to the assessment of quantitative composition of drugs based on natural peptides containing glycosaminoglycan-peptide complex

Vengerovich N.G., Efimov N.V., Rogozhina N.I., Stepchenkov V.I.


The  preparations  isolated  from  the  biomaterial  of  farm  animals  and  fish  were  studied. These  preparations (rumalon,  alflutop)  cannot  be  obtained  in  equal  proportions  and  concentrations  during  their  production. An algorithm for quantitative determination of components of peptides of natural origin based on the study of model drugs containing a glycosaminoglycan-peptide complex has been developed. Using infrared spectroscopy and high performance liquid chromatography, the concentrations of chondroitin sodium sulfate, hyaluronic acid, glucosamine, protein, free amino acids and amino acids that make up the peptides (alflutop and rumalon) were established. In comparison with the majority of monocomponent drugs registered in the territory of the Russian Federation and containing chondroitin sodium sulfate at a concentration of 100 mg/ml, glucosamine drugs (200 mg/ml), hyaluronic acid drugs (10 mg/ml) it was found that the main active components of the studied drugs were more than 50, 100 and 7 times smaller. At the same time, the preparations under study contained a large percentage of free amino acids or short-chain peptides. It indirectly suggests their participation in the clinical efficacy of drugs based on natural peptides.

The developed algorithm for quantitative determination of components of peptide preparations of natural origin, including common and generally available methods sequence (identification of samples by infrared spectroscopy in comparison with standard samples, quantitative determination of chondroitin sodium sulfate, hyaluronic acid, glucosamine, protein and amino acids by infrared spectroscopy and highly efficient liquid chromatography) is advisable to use when determining minimum specific values of contents (concentrations) of active components and adjuvants of peptide origin in studies and registration of drugs based on them, as well as to justify ways in order to search and explain the mechanisms of action of such compounds.

Pharmacy Formulas. 2020;2(1):8-15
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Morpholine derivatives as potential agents for neurological manifestations of nervous system diseases

Prikhodko V.A., Sysoev Y.I., Okovityi S.V.


Diseases of the nervous system, especially those of vascular, traumatic, and neurodegenerative nature, are characterized by high prevalence, disability and mortality rates, and therefore have a particularly big medical and social impact. Currently, pharmacotherapy options for these diseases are limited to a relatively small number of clinically proven drugs, which is largely due to the difficulties associated with the translation of preclinical studies results. This explains the essential importance of discovering and developing new drugs, both effective and safe, that could be used to reduce clinical manifestations of neurological disorders. The present review is aimed to give a detailed account of several biologically active derivatives of morpholine, a six-membered heterocyclic compound. As demonstrated by a number of in vitro and in vivo studies using cell and animal models, morpholine derivatives should be considered viable drug candidates for a broad range of neurological diseases.

Pharmacy Formulas. 2020;2(1):16-35
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Modern polymers in prolonged release tablet technology

Kotsur J.M., Flisyuk E.V.


Currently, the delivery systems of second and third generation are of particular interest among pharmaceutical forms. Second generation pharmaceutical forms include systems with prolonged release of the active substance, third generation pharmaceutical forms include systems with controlled release. A slow continuous release of a medicinal substance may be achieved by using special excipients or by using special technologies.

For the production of tablets with prolonged release, the most common are special excipients, namely, polymers and their compositions.

The use of polymers as carriers of pharmaceutical substances used to program the kinetic frequency and location of the release is known since the middle of XX century [9]. To date, significant progress has been made in the use of polymers to prolong the release: the influence and interaction of polymers and drugs have been studied, the mechanisms of drug release have been studied, ways of programming release kinetics using various properties of polymers, etc.

In the article the modern state in the field of technology of tablets with prolonged release is considered. Advantages of prolonged release, mathematical models for description of drug forms with prolonged release are described. Technologies of tablets with prolonged release, types of delivery systems and mechanisms of release of an active pharmaceutical ingredient are considered.

The article presents modern polymers that are used in the technology of tablets with prolonged release. The classification of polymers in relation to water and to physiological liquids is presented.

Pharmacy Formulas. 2020;2(1):36-43
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Processing and evaluation of qualitative data of the pharmaceutical market using economic and statistical methods

Umarov S.Z.


In competitive conditions of the pharmaceutical market, a significant factor is the problem of identifying market trends; the need to identify competitors and threats, resources assessment. For this purpose, it is necessary to constantly collect and generate data on the basis of which an informed decision is developed by the heads of pharmacy organizations. However, a certain category of pharmaceutical management believes that business decision-making should be based solely on intuition and practical experience, which excludes the use of any quantitative information.

In the course of the data study from the retail sector of the pharmaceutical market, the possible formats of practical application are considered.

The totality of data characterizing the business processes in the pharmaceutical market was evaluated by the degree of structure. A classification method was used to characterize the sampling based on the primary data processing, methods of cross tabulation and frequency analysis were implemented.

The nature of the data is clearly illustrated, which makes it possible, if necessary, to obtain new quantitative indicators, such as, for example, “Total number of sales by visitor groups”, “Average number of sales”, etc., characterizing pharmaceutical business processes.

The processing of high-quality data of marketing information about the pharmaceutical market by the methods of frequency analysis and cross tabulation allows one to determine reasonably accurate the preferences of visitors of a particular category, which makes it possible to optimize the assortment policy and effectiveness of the pharmaceutical company as well.

Pharmacy Formulas. 2020;2(1):44-52
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Biomedical Sciences

Evaluation of the 223Ra-dichloride biodistribution models for the assessment of the doses from internal exposure

Vodovatov A.V., Chipiga L.A., Petrova A.E., Stanzhevsky A.A.


Prostate cancer is the most common men urogenital tumor. For most patients with the disseminated neoplastic process in the prostate after the hormonal therapy, the disease gradually progresses in the form of castration-resistant prostate cancer (mCRPC). The use of 223Ra agents is aimed at the treatment of the bone lesions as part of palliative therapy. The physical properties of 223Ra significantly complicate the require direct radiometry for patients with alpha emitters. Hence, the distribution of 223Ra in the body should be evaluated based on the dedicated biodistribution models. The aim of this study was to review and analyze the existing approaches to the evaluation of the biodistribution of 223Ra and its pharmaceutical forms (223Ra-dichloride) for the further assessment of absorbed doses in radiosensitive organs and tissues. The study includes the mathematical models for the estimation of the absorbed doses in various organs and tissues of the body. A review of three different 223Ra biodistribution models is presented: two ICRP models for occupational exposure and a model based on the results of an experimental assessment of 223Ra distribution in patients with mCRPC. It was indicated that the latter model is in good agreement with the results of direct radiometry of patients. A significant drawback of all models is the simulation of the red bone marrow and bone surface as single chambers. During the radionuclide therapy, 223Ra will specifically accumulate in bone metastases, instead of being evenly distributed in the skeleton. Hence, the use of any of the reviewed models will lead both to a significant overestimation of the absorbed dose in a healthy part of the bone surface and red bone marrow, and to an underestimation of the absorbed dose in bone metastases. Currently, this problem has not been solved. That requires the development of new improved models that consider the accumulation of 223Ra in the healthy part of the skeleton and in skeletal metastases.

Pharmacy Formulas. 2020;2(1):54-69
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Biological sciences

Pathogenic substantiation of application of erythropoietin modified forms and peptide analogues as cytotprotectors

Ivanov I.M., Nikiforov A.S., Vengerovich N.G., Perelygin V.V., Proshina Y.A.


Provides a review of the evidence from experimental and clinical studies on the blood-forming and non-blood-forming tissue protective effects of erythropoietin. Information on its side effects (stimulation of tumor growth, autoimmune reactions, arterial hypertension, etc.), limiting the clinical use as a cytoprotector, is summarized. Well-known modifications of the erythropoietin molecule with a tissue protective effect are considered, in particular, desialylated (asialoEPO), carboxylated (CEPO) and glutaraldehyde (GEPO) cytokine analogues.

The results of biomedical studies describing the tissue protective effects of these compounds, as well as possible mechanisms of their receptor action, are presented. The article discusses the main short-chain erythropoietin mimetics that reproduce individual active regions of cytokine amino acid sequence and contain from 11 to 25 amino acids: Helix B, ARA290, Eportis, Epopeptide-ab, MK-X, Epobis, NL100.

The biochemical mechanisms of cytoprotective action of erythropoietin and its derivatives are considered, including binding to the heterodimeric receptor of non-blood-forming tissues and activation of intracellular signaling molecules possessing properties of apopotosis inhibitors.

It was noted that the tissue protective effect of erythropoietin in vivo is observed in hemostimulating doses and is accompanied by side effects. At the same time, the use of modified forms of erythropoietin and its short-chain peptide analogues, which have a high affinity for the isoform of the erythropoietin receptor of non-blood-forming tissues and do not have hematopoietic properties, allows avoiding the development of side effects and reducing effective doses by 10-20 times.

Pharmacy Formulas. 2020;2(1):70-81
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Information and Prevention

Aspects of pesticide and agrochemical application in the field of beekeeping

Paramonov S.G.


The problem of uncontrolled use of pesticides and agrochemicals is now becoming widespread, and their use is called the second most important cause of death of all insect biomass around the globe.

Pharmacy Formulas. 2020;2(1):82-84
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Moses Efimovich Bergolts: first rector of the revived institute

Narkevich I.A., Stepanov S.V., Zvyagin Y.Y., Vorobeva S.A., Perelygin V.V., Dobrova D.O.


The St. Petersburg chemical and pharmaceutical Institute has passed several periods in its development. After the difficult but glorious formation of the Petrograd chemical and pharmaceutical Institute in 1919-1924, the time came for its existence as a faculty within the Leningrad University, and from 1925-the 1st Leningrad medical Institute

Pharmacy Formulas. 2020;2(1):92-97
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Valery Galynkin: "a Scientist should also be a practitioner»

Zvyagin Y.Y.


On January 11, 2020, friends and colleagues celebrated the eightieth anniversary of Valery Abramovich Galynkin, one of the leading specialists in the field of pharmaceutical and food biotechnology in Russia. About him our today's story

Pharmacy Formulas. 2020;2(1):98-103
pages 98-103 views

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