Composition based on aluminum oxide and polydimethylsiloxane matrix for enhancing drug targeting

Methodological approaches developed at Research Institute of Clinical and Experimental Lymphology for a number of years allow formulating the importance of embedding active pharmaceutical ingredients (API) in the structure of porous carriers (sorbents). The composition of the carrier and API is an enteral system for prolonged dosing of pharmacological agents, which allows providing a specific pharmacological effect and safety of use. The pores of the media (sorbents) act as containers for API. This is especially important for rapidly absorbed drugs, which include, for example, lithium preparations that are used in narrow concentration limits due to their side effects. At the moment, an innovative technology for creating new medicines with an improved combination of efficiency and safety (pharmacological upgrade) has been developed and implemented. The essence of the technology is to create a composition of aluminum oxide and polydimethylsiloxane (matrix) and an active pharmacological ingredient (API). A study of two drugs based on matrix / lithium citrate and matrix / melatonin showed continued specific pharmacological activity of API, better pharmacokinetics, and better safety parameters. The matrix of aluminum oxide and polydimethylsiloxane provides an upgrade of the pharmacological properties of drugs for the dosed and safe delivery of API to the zone of their therapeutic effect

Silver containing sorbents: Physicochemical and biological properties

New silver containing sorbents, based on mineral carriers, such as alumina and silica systems with a meso- and macro- porous structure, have a higher mechanical resistance and, hydrophilic and hydrophobic chemical composition of the surface. These sorbents are easy to find and relatively inexpensive, compared to their known equivalents. They are furthermore characterised by high specific surface and simple preparation, whilst the addition of silver considerably increases their antiseptic activity. The results of research of the physical, chemical and biological properties of the developed substances, as well as bio-comparability of sorbents with biological tissues, are presented in this paper. The modified material acts simultaneously as the carrier for active substances to the area of therapeutic application and as a sorbent used to remove toxic agents from such areas. This approach led us to modify the sorbent, and prolong the delivery of substances such as silver, as an effective antibacterial and antimycotic agent

Estimation of acute toxicity of a drug based on the complex of lithium citrate, polymethylsiloxane, aluminum oxide

Research Institute of Clinical and Experimental Lymphology has developed an innovative drug based on a complex of lithium citrate, polymethylsiloxane and aluminum oxide (LOAP). Lithium-based drugs are effective in treating bipolar disorders. However, the toxic effects of lithium cause a “narrow therapeutic window”, which limits its clinical use. The creation of the drug LOAP was aimed at creating a prolonged form with a slow release of lithium to reduce toxic properties and use lithium citrate as an active pharmacological agent. At the moment, the lithium complex has no analogues. The purpose of the study was to study the parameters of acute toxicity of the LOAP. Material and methods. When studying acute toxicity, drugs were administered once intragastrically to mice and rats at doses of 12000, 10000, and 5000 mg/kg. Results. A single administration of drugs intragastrically through a probe in the maximum possible doses to mice and rats did not cause the death of animals and did not cause a locally irritating effect on the gastric mucosa. LOAP can be assigned to hazard class 4 (GOST 12.1.007-76)

STUDYING THE POSSIBLE MUTAGENIC PROPERTIES OF NEW MEDICINE ON THE BASIS OF COMPLEX LITHIUM CITRATE, ALUMINUM OXIDE AND POLYMETHILSILOXANE

Aim of the study was to investigate the possible mutagenic properties of a new drug based on a lithium-containing substance – a complex of lithium citrate, polymethylsiloxane and aluminum oxide. Material and methods. Methods for testing mutagenicity using chromosomal aberrations in the bone marrow cells of CBA mice and somatic recombination in Drosophila melanogaster were used. Results. It was shown that a single intragastric administration of drug at a dose of 5000 mg/kg and a fivefold course of administration at a dose of 400 mg/kg to CBA mice did not increase the level of cytogenetic disorders in bone marrow cells. The study of the lithium complex drug in a somatic mosaicism test revealed that the preparation at a dose of 2000 mg/kg does not increase the frequency of mutations in Drosophila melanogaster. Conclusion. A single intragastric administration of the studied drug at a dose of 5000 mg/kg and its course administration (400 mg/kg × 5) do not increase the level of cytogenetic disorders in the bone marrow cells of CBA mice. In the somatic recombination (mosaicism) test system on D. melanogaster, no increase in the appearance of mutant setae and spots on the body and head was observed when using yellow and singed markers. The results of the study indicate that the studied drug does not have mutagenic properties

Whole organisms or pure compounds? entourage effect versus drug specificity

As the therapeutic use of sacred plants and fungi becomes increasingly accepted by Western medicine, a tug of war has been taking place between those who advocate the traditional consumption of whole organisms and those who defend exclusively the utilization of purified compounds. The attempt to reduce organisms to single active principles is challenged by the sheer complexity of traditional medicine. Ayahuasca, for example, is a concoction of at least two plant species containing multiple psychoactive substances with complex interactions. Similarly, cannabis contains dozens of psychoactive substances whose specific combinations in different strains correspond to different types of therapeutic and cognitive effects. The “entourage effect” refers to the synergistic effects of the multiple compounds present in whole organisms, which may potentiate clinical efficacy while attenuating side effects. In opposition to this view, mainstream pharmacology is adamant about the need to use purified substances, presumably more specific and safe. In this chapter, I will review the evidence on both sides to discuss the scientific, economic, and political implications of this controversy. The evidence indicates that it is time to embrace the therapeutic complexity of psychedelics.2019-07-3

EFFECTS OF THE LITHIUM – CONTAINING SORBENT ON TERMS OF BEHAVIORAL REACTIONS UNDER CHRONIC ALCOHOL INTOXICATION MODEL

Lithium preparations are widely used for stabilize mood in case of bipolar affective disorder. Currently neuroprotective and neuroregenerative effects of lithium are of interest as in case of acute brain injury, also in chronic neurodegenerative diseases such as dementia, alcoholism, Alzheimer disease, etc. [1–5]. In clinical practice use of lithium preparations is limited due to difficult adjustment of drug dosage, necessity of monitoring its concentration in blood, side effects development as a result of accumulation of lithium in a body. For the purpose of improvement of pharmacologic properties lithium is combined with other agents (for example modifying sorbent) thus it can produce longer-term and more harmless (less side reactions) effect in the long view. Lithium immobilization on sorption basis will allow to use sorbent as detoxicant and carrying agent of drugs to body. The purpose of the work is studying the effect of the lithium – containing sorbent on terms of behavioral reactions under chronic alcohol intoxication model.Materials and methods. During the work we used nonlinear mice – males, which weight 25–30 g (180 animals). Chronic alcohol intoxication was precipitated via 40% proof spirit injections (oral supplementation in quantity of 3 g/kg during 2 weeks), additionally mice drunk 5% proof spirit from drinking bowl. Each experimental group consisted of 10 animals. Study drugs were inserted inside while ethanol injecting. Control animals were inserted 0,9% salin solution. Emotional state of animals was assessed through forced swim test, short – term memory assessment was performed through conditioned passive avoidance reflex. Effect of chronic alcohol intoxication on the parameters of conditioned reflex activity was measured every 7 days.Results. It was found that the investigated lithium-containing sorbent increases: the number of mice are trained passive avoidance reflex, remembering percent of electric shock animals compared to the negative control , and – the duration of the latent time of immobility in comparison with the negative control.Conclusion. The proposed formulation of lithium (immobilized on a sorbent ) has a complex neurotropic action, showing antitoxic properties against a background of long-term administration of ethanol

CHARACTERISTICS OF CLINICAL PICTURE AND BIOLOGIC FEATURES OF RARE BREAST CANCER FORMS

Low incidence and difficulties of histological type identification of rare breast cancer forms preoperatively renders paramount importance to the detailed study of all cases revealed. Within the bounds of the research which is under the way in our center, we carried out an analy- sis of patients’ records treated in the N.N. Blokhin Russian Cancer Research Center from 1985 to 2005. Overall, 1053 cases of rare breast cancer forms were diagnosed including 364 patients with tubular, 231 — mucous, 190 — medullar, 126 — papillary and 142 — metaplas- tic carcinomas. The article discusses the issues of clinical course, presentation, treatment and prognosis of rare forms of breast cancer

Capabilities of percutaneous biopsy methods to preoperatively verify breast microcalcinates

Information on the morphological type of a tumor is of crucial importance for successfully planning the treatment of patients with breast cancer (BC). Technological progress in the past decade has led to quality improvement in the diagnosis of particularly nonpalpable BC, one of whose manifestations is microcalcinates. Adequate use of mini-invasive procedures for obtaining materials for morphological analysis is favorable for extending the capabilities of accurate preoperative diagnosis verification to effectively plan a patient treatment and rehabilitation program