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C.
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Editorial
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1
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Contents
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2-5
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MOLECULAR
DYNAMICS STUDY OF QUERCETIN AND SOME OF ITS SUCCINYL DERIVATIVES IN
AQUEOUS
SOLUTION
Lisnyak Yu. V., Martynov A.
V.
Introduction. Numerous and diverse biological
activity of flavonoid quercetin motivates interest to the peculiarities
of its
structure as a prerequisite for understanding its structure-function
properties
which are not fully understood today and remain an object of
physico-chemical,
biological and structural studies. In
the solid
state, quercetin is known to exist in two crystal forms, quercetin
monohydrate
and quercetin dihydrate. But there are only scare data on its structure in the
aqueous solution.
High-throughput screening studies indicated that quercetin belongs to promiscuous
inhibitors and is hypothesized to form aggregates comprising of many
individual
molecules. To investigate the peculiarities of structure and
intermolecular
interactions of quercetin as well as some of its succinyl derivatives
in liqiud
phase we carried out molecular dynamics simulation of their behavior in
the
aqueous solution. Methods . Molecular dynamics simulations and the data analysis
were performed by molecular modeling program YASARA Structure. Molecules of quercetin or its succinyl derivatives were
randomly placed
within a dodecahedral simulation cell. Simulation cell was filled with
TIP3P
water molecules to reach 10 % concentration of quercetin or its
succinyl
derivatives. Na+ and Cl¯ counterions were added to neutralize the
system and to
reach ion mass fraction 0.9% NaCl. The molecular system was
energy-minimized
using AMBER14 force field with 8 Ǻ force cutoff for dispersion
interactions. To treat long-range electrostatic interactions the
Particle Mesh Ewald algorithm was used. After a short steepest descent
minimization, the procedure continued by simulated annealing
minimization. The
molecular dynamics simulations were run in NPT ensemble at 300 K and pH
7.4
using a multiple timestep of 2.5 fs for intra-molecular and 5 fs for
inter-molecular forces. For each molecular system, trajectories were
computed
for 100 ns. Results and discussion.
From the first nanoseconds of simulations, molecules of quercetin as
well as
succinyl-quiercetins approached one another and began to self-organize
into a
compact aggregate that remained stable during further simulation time.
Driving
forces of
the aggregate formation were the hydrophobic stacking interactions
between
aromatic systems of neighbor molecules. Due to a bulky succinyl
substituent the
aromatic systems of neighbor succinyl-quercetin molecules could not
overlap
optimally to ensure efficient stacking interactions that resulted in
the higher
mobility of the molecules in the aggregate and the possibility to form
easily
intermolecular H-bonds. Behavior of
completely succinylated quercetin, 3,4´,5,5´,7-succinyl quercetin, in
aqueous
solution was essentially different. In this case, molecules remained
free the
majority of time and sometimes formed short-lived complexes between two
or
three molecules. The driving
forces of the complex formation are hydrophobic and ionic
intermolecular
interactions. Hydrophobic interactions occurred between aliphatic
residues,
between aliphatic residues and aromatic systems, and also between
aromatic
systems. The later took place in T-shape ring
arrangement. Ionic interactions
between molecules of completely succinylated quercetin are mediated by
their
interactions with one or two Na+ ions. Conclusions. Results of our molecular dynamics simulations of the behavior of quercetin and some of its succinyl
derivatives in aqueous solution are in line with the hypothesis of the
self-organized aggregate formation by molecules of promiscuous
inhibitor
quercetin and reveal the peculiarities of the structure and
intermolecular
interactions within the aggregates in case of quercetin and the
combinatorial
mixture of its succinyl derivatives. These data may be useful for the
search of
new drugs based on quercetin as a lead compound.
Keywords: quercetin,
succinylated
quercetin, supramolecular aggregates, molecular dynamics.
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6-15
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EPIDEMIOLOGICAL FEATURES OF THE MEASLES
IN KIROVOGRAD REGION
in 2004 – 2015
Operchuk N.I.
Introduction.The
incidence of measles in Ukraine remains an actual problem. Measle is
related to vaccine - controled infections. However, low levels of
imunization
of the child population by planned measles vaccine, insufficient
provision of
immunobiological drugs (vaccines) in recent years, anti-vaccine
companies
contribute to the increase of the measles morbidity in
Ukraine.Prominent
scientist L.V. Gromashevsky spoke about measles, which is a "disease of
unique distribution". In the
implementation
of the Program for the elimination of measles, an important role is
assigned to
laboratory diagnostics as an integral part of epidemiological
surveillance,
which assures laboratory confirmation of all cases of measles disease. The purpose of the study:
to analyze the peculiarities of the epidemic situation
of measles in the Kirovograd region, the state of laboratory diagnosis
of
measles. Materials and methods: Data from the official statistical
reporting of
the state institution "Kirovograd Regional Laboratory Center of the
Ministry of Health of Ukraine" (forms №1, № 2, № 40), demographic
annual
indicators of the State Statistics Service of Ukraine and the Main
Department
of Statistics in Kirovograd region.
Results and discussion: The epidemiological analysis
of measles incidence in the Kirovograd region in the period 2004-2015
and the
results of laboratory diagnosis of cases in measles in this period of
observation have been carried out.The peculiarities of manifestation of
the
epidemic process of measles in the Kirovograd region require a detailed
study
also because Kirovograd region is the only region in Ukraine with rich
natural
reserves of uranium ore. The presence of uranium raw materials on the
territory
of the region in turn increases the natural radiation background.The
technological process of which enhances natural ionizing radiation
technogenously. The effect of technogenic contamination by natural
radionuclide
of the environment and the increased natural radiation background on
the human
immune state, as well as the manifestations of the epidemic process of
the
measles, the influence on the properties of viruses is not excluded.
From 2004
to 2015, the incidence of measles in Ukraine ranged from 0.06 (2009) to
90.7
per 100 thousand population (2006). During this period, there were
twopeaks of
the measles in Ukraine: in 2006 - 90.7 per 100 thousand and in 2012 -
27.9 per
100 thousand populations.During 2007-2010, the incidence of measles in
Ukraine
gradually decreased (2.15, 0.11, 0.06, and 0.08 per 100 thousand
populations,
respectively). The dynamics of measles morbidity in the Kirovograd
region for
the period 2004-2015 is characterized by unstable levels. The trend of
the
morbidity of the population of the region repeats the course of measles
morbidity in Ukraine with a slight decrease or excess. In this period,
the
incidence rates of the Kirovograd region were lower than the Republican
figures
in 2005 (by 49%); 2007 (by 67%); 2008 (by 9.0%); 2011 (by 76%); 2013
(by 67%)
according to similar indicators in Ukraine. In 2010 and 2015, the
incidence of
measles in the Kirovograd region was not recorded. In all other years
of the
observation period, the incidence rates of measles in the Kirovograd
region
were higher than in Ukraine as a whole. In the region, one peak of the
incidence of growth was observed in 2006, when the incidence rate in
the
Kirovograd region (147.9 per 100 thousand populations) exceeded the
similar
indicator in Ukraine (90.7 per 100 thousand populations) in 1, 63
times. During
this time, 1,741 inhabitants of the region suffered from measles,
including -
472 (21, 1%) children and 1269 (78,9%) adults. If the share of
children's
population in the overall incidence of measles in the Kirovograd oblast
amounted to 85.7% in 2007; in 2013 - 62.5%; in 2005 - 53,6%; then in
2006 -
25.2%; in 2011 - 28.6%; in 2014 - 36.8%.
The laboratories confirmation of a clinical diagnosis in
the early
stages of the development of the outbreak improving the effectiveness
of
epidemiological surveillance of the measles promotes. 214 samples of
blood
serums from patients with suspected measles and a clinical diagnosis of
"Measles" were received to the virusological laboratory of the
Kirovograd Regional Laboratory, accounting for 12.3% of all reported
cases of
measles in 2004-2015.214 samples (100%) were investigated for the
detection of
antibodies to the IgM class of the virus of the measles.In the study of
blood
serum antibodies of the class IgM found in 42.5% (91 people). Thelevels
ofimmunizationagainst the measles population in the Kirovograd region
since
2009 were insufficient and below 95%. The plan for vaccination against
measles
in children in 1 year is fulfilled: on 75,9% (2009), 52,8 (2010); 62.3%
(2011);
89, 8% (2012); 80.7% (2013); 86.5% (2014); to 39.6% (2015). The plan of
the
revaccination plan for children 6 years of age is secured by 71.6%
(2009); 31,
5% (2010); 31.0% (2011); 89.2% (2012); 77.9% (2013); 73.0% (2014);
27.4%
(2015). Conclusions. Despite
the fact that the intensity of the
epidemic process of measles in the Kirovograd region during the last
epidemic
peak was significantly lower than in Ukraine in general, the marked
tendency to
increase the incidence among children and insufficient coverage of
children by
vaccination and revaccination is an unfavorable prognostic sign. This
refers to
the risk of further growth of the intensity of the epidemic process at
the
expense of those age groups of the population who must be protected in
accordance with the vaccination calendar, and the loss of the measles
infection
as a "managed" status. The current situation requires immediate
action to restore immunization in the country in full.
Keywords:
measles,
epidemiology, Ukraine, Kirovograd, year 2004-2015
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16-20
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ANTISEPTIC SPRAY BASED ON STABILIZED SILVER PARTICLES: AN
ANALYSIS OF ANTISEPTIC PROPERTIES AND COMPREHENSIVE COMPARISON
Manuilov A.M., Martynov A.V.
Introduction. It's known that some antiseptic sprays based on alcohols
can provoke the
formation of multi-resistant strains of pathogenic microorganisms. In
addition,
alcoholic antiseptics has a number of restrictions to use, for example,
they
can't to be used in even the presence of micro-trauma on the skin,
their
ingression into the body and mucous membranes is unacceptable.
Alternative can
be natural antiseptics based on colloidal silver or silver
nanoparticles, as
well as silver in ionic form. However, such antiseptics has low
efficacy
against the most dangerous strains. Company Modern Biochem Technologies
Ltd.
announced the development of a portable device that generates a natural
and
safe antiseptic Dew, based on stabilized silver particles. Antiseptic
Dew
surpasses the vast majority of antiseptics based on silver, and is not
inferior
in effectiveness to antiseptics based on alcohols. This work is devoted
to
testing the declared characteristics of Dew and its comparison with
antiseptics
based on colloidal silver, silver nanoparticles and isopropyl alcohol. Materials and methods. To test the
antiseptic effect of these agents, we used four test strains from the
American
Type Culture Collection: E. Coli ATCC 25922, Staphylococcus Aureus ATCC
25923,
Candida Albicans ATCC 885-653 and Proteus Vulgaris ATCC 4636 with
billion
concentration of colony forming units in 1 ml (108 – 109
CFU/mL, ln CFU/mL = 19.57 ... 20.72). Sowing and screening of cultures
were
performed on sterile Petri dishes according to the standard procedure.
Antiseptic Dew was prepared by prototype provided by Modern Biochem
Technologies. The antiseptics of comparison were purchased in Kharkiv,
Ukraine.
The treatment of contaminated surfaces was performed using mechanical
pump
sprayers. In accordance with the internal protocol, 1 ml of antiseptic
was
sprayed from the distance of 10 cm onto the infected surface. To
determine the
silver content in the Dew, we were used atomic-absorption spectrometer
MGA-925MD. Samples for analysis were prepared in accordance with the
standard
protocol for operation on MGA-925MD. Results
& Discussion. For the research we conducted more than 200
microbiological
tests. Based on the results of these tests, we can conclude that Dew is
indeed
superior to other silver-based antiseptics. Also, we can note that in
one case,
Dew surpassed the effectiveness of the antiseptic based on isopropyl
alcohol,
but in the second case was slightly less effective. Dew is effective
against
all four test strains, and the decrease in microbial load after
treatment is
very substantially - from 109 CFU/mL to 0-101
CFU/mL. The
concentration of silver in Dew does not exceed 1.45 ppm and is on
average 20
times lower than that of the other tested antiseptics based on silver. Conclusion.
Based on the data obtained, we conclude that Dew is a
promising
antiseptic. Note that the prototype generated the antiseptic with
stable
characteristics throughout the study. Antiseptics of comparison were
shown
their effectiveness against test strains, however in one case Dew was
surpassed
them all in efficiency. In conclusion, we note that we recommend
conducting
in-depth tests, primarily aimed at determining the effect of Dew in
vivo. We
also recommend testing Dew on hospital-strains or other resistant
strains.
Keywords: spray, antiseptic, silver, antimicrobial
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21-27
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CORRECTION OF LARGE INTESTINE DYSBIOSIS IN PATIENTS WITH
ACUTE HEPATITIS
B
Sklyar А.I., Kalinichenko S.V., Melent’yeva K.V.,
Torianyk I.I., Popova
N.G.
Introduction.
Viral hepatitis is one of the global challenges for
modern medicine. Among them, hepatitis B (GB) remains one of the most
widespread viral diseases of the present day. According to the WHO
estimates,
more than 1/3 of the world's population (2 billion people) has
serological
evidence of current or transmitted HBV infection, of which 350 million
are
chronically infected. Separate studies have identified the state of the
colon
biocenosis in patients with acute hepatitis and found that dysbiotic
lesions of
varying degrees are found in patients with viral hepatitis in 73.3% -
96% of
cases [6-8]. Disturbances of the quantitative and qualitative
composition of
the microflora reduce the detoxification function of the intestine and
increase
the toxic load on the liver, which, in turn, negatively affects the
development
of the basic pathological process. The
aim of the work was to determine the degree of dysbiotic changes in
the
microflora of the large intestine and to evaluate the effectiveness of
their
correction with a symbiotic drug in patients with acute hepatitis B. Materials and methods. To perform the
task, 108 patients with acute hepatitis B, aged 18-69 being on hospital
treatment
at Kharkiv Regional Clinical Hospital of Infectious Diseases, have been
examined. The diagnosis has been set on the basis of clinical
anamnestic,
epidemiological, laboratory and instrumental data. The etiological
verification
of the diagnosis has been performed by detecting specific serological
markers
of hepatitis B (HBsAg, HBeAg, anti-HBc IgM, by the ELISA method). The
diagnosis
of GHB and its clinical and pathogenetic variants of the course, form
and
degree of severity have been determined according to the International
Statistical Classification of Diseases and Related Security Problems
Health
(ICD-10, version 2006). According to the purpose of study the patients
have
been divided into groups as follows:
group A - the main one, where patients have additionally
been taking
symbiotic besides who the basic treatment; group
B - patients to whom basic therapy has
been applied. Thus, 2 groups of 54
patients have been formed. The control group, which did not differ from
the
groups of patients by age and gender, has been made up of 17 clinically
healthy
persons. For patients of group A
patients we have been using symbiotic — Bifilact Extra, TM "Ariadna",
Ukraine, certificate of registration No. 05.08.07 / 4089 of 02.10.2000
containing Lactobacillus acidophilus
and Bifidobacterium bifidum. Determination
of the qualitative and
quantitative composition of
microbiocenosis of the large intestine has been carried
out in
accordance with current normative documents as per generally accepted
methods.
The degree of dysbiotic disturbances was determined by V.M. Bondarenko
in 2007.
Microbiological studies of the material have been conducted in dynamics
before
the treatment and 7 days after the end of the course of treatment with
the
symbiotic.
Statistical
processing of the data was carried out using the Statistics-10 software
package, Microsoft Office Excel 2003. Results.
In all patients, there was an acute cyclic course of HBV
infection with
clinically expressed jaundice in the background of cytolysis syndrome. By results of researches of the species
composition of the microflora of the colon in jaundice period of AHB, a
violation of the microecology of this biotope of different degrees was
found in
96.3% of patients. It turned out that the degree of dysbiotic shifts
did not
depend on the severity of hepatitis. About half of patients had
dysbiosis of
grade III. Analyzing the species composition and population level of
the
microflora of the colon in patients with acute hepatitis B in the
jaundice
period, there was elimination or severe deficiency of bifidobacteria
and
lactobacilli and the vegetation of opportunistic bacteria. But the most
common
cause of local microecology was Candida spp, it was determined in 30,8
% of the
total number of identified pathogenic microorganisms. In addition, the
proportion of Candida spp in violation of the microecology of the large
intestine increased in the dynamics of the disease to 42.3%, which was
evidenced in the period of reconvalescence. The appointment of a
symbiotic
resulted in a reduction in the clinical manifestations of dysbiosis in
63,0 %
of patients compared to patients receiving baseline therapy. The appointment of a symbiotic resulted in a
reduction the length of stay of patients of mild severity and patients of average severity in the hospital
compared to patients receiving baseline therapy, p ˂ 0,05. Conclusions. By results of researches of the species composition of
the microflora of the colon in jaundice period of AHB, a violation of
the
microecology of this biotope of different degrees was found in 96.3% of
patients. About half of patients had dysbiosis of grade III. The
appointment of
a symbiotic resulted in a reduction in the clinical manifestations of
dysbiosis in 63,0 % of patients compared to patients receiving baseline
therapy. The appointment of a
symbiotic
resulted in a reduction the length of stay of patients of mild severity
and patients of average severity in the
hospital compared to patients receiving baseline therapy.
Keywords: acute hepatitis B, large intestine,
microbiocenosis, complex treatment, symbiotic.
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28-31
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THE ROLE OF EPSTEIN-BARR VIRUS AND HUMAN ENDOGENOUS
RETROVIRUSES IN THE
PATHOGENESIS OF MULTIPLE SCLEROSIS
Zelenska A. D., Tupotilov O. V., Kolyada T. I.
Multiple sclerosis (MS) is an autoimmune demyelinating
disease of the central
nervous system (CNS), the development of which is associated with the
action of
a large number of pathogenetic factors which role can vary
significantly at
different stages of the disease. Although the etiology of MS still
remains
unclear, in recent years the hypothesis of the pathogenetic role of
Epstein-Barr virus (EBV) and human endogenous retroviruses, such as
MSRV /
HERV-W, is actively considered. EBV has a unique ability to infect,
activate,
and latently persist within B lymphocytes during human life. Immune
control of
EBV infection in healthy organisms is realized through humoral and
cellular
mechanisms – EBV virions are destroyed by neutralizing antibodies, and
proliferating and lytically active EBV-infected B cells are the targets
of
specific CD8+ T cells. At the same time, EBV remains latent for most of
the
life of the infected individual, expressing a single gene (EBNA1)
within memory
B cells. EBNA1 protein is not well recognized by CD8+ T cells, allowing
infected memory B cells to avoid detection. In addition to
epidemiological
data, association of EBV with MS is indicated by a significant increase
in IgG
titres to EBV antigens, mainly to EBNA1, in serum of patients a few
years
before the onset of clinical manifestations of the disease. Although
the data
on the presence of EBV in the CNS remain controversial due to a number
of
methodological difficulties, a number of studies have shown the
presence of
EBV-infected B cells in the CNS, as well as effector CD8+ T cells
specific for
them in meningeal inflammatory infiltrates and white matter lesions in
brain
samples of MS patients. At the same time, the EBV bystander damage
hypothesis
which considers CNS damage in multiple sclerosis as a result of
EBV-targeted
cytotoxic reactions of CD8+ T cells, does not explain the autoimmune
nature of
MS, although secondary autoimmune responses could develop as a result
of
sensitization to CNS antigens released after a cytotoxic response
directed to
EBV elimination causing bystander neuronal damage. It also does not
explain why
the EBV-targeted T cell immune response sufficient to cause bystander
CNS
damage does not eliminate EBV-infected B cells from the CNS. It was
found that
subpopulations of EBV-specific CD8+ T cells in MS patients show signs
of
depletion, increasing with the duration of the disease, which
apparently allows
EBV-infected B cells to accumulate in the CNS and leads to the
formation of a
vicious circle, in which the initially defective T cell response is
aggravated
by depletion of T cells as a result of a constant high viral load in
CNS. M.
Pender has proposed a hypothesis of the pathogenesis of MS according to
which
MS is caused by the accumulation in the CNS of autoreactive
EBV-infected B
cells that are capable of self-sustaining proliferation, production of
pathogenic antibodies in the CNS, and providing costimulatory and
survival-promoting signals to autoreactive CD4+ T cells. But it remains
unclear
what type of CD8+ T cells is dominant in CNS lesions in patients with
MS -
specific to EBV, specific to myelin proteins, or both types of cells.
However,
the delay between seroconversion in the EBV-positive status in late EBV
infection and the development of MS may indicate the presence of
additional
factors in the development of the disease. In recent years, a number of
studies
indicate a possible pathogenetic role of endogenous human retroviruses
(HERV)
in MS. In infectious mononucleosis, the increased expression of
MSRV/HERV-W in
peripheral blood mononuclear cells has been observed, moreover, a
direct
correlation has been found between levels of IgG to EBNA-1 and levels
of
MSRV-specific mRNA expression. Binding of the EBV caused activation of
MSRV /
HERV-W in peripheral blood mononuclear cells and in astrocytes.
Activation of
MSRV/HERV-W was also revealed in inflammatory context and in
neuropathogenic
processes in MS. In the peripheral blood mononuclear cells culture of
MSRV-positive individuals, expression of MSRV was activated by the
action of
pro-inflammatory cytokines such as TNF-α, IL-6, and IFN-γ, and
significantly
decreased by IFN-β. At the brain level, HERV-Wenv activates Toll-like
receptors
(TLR4) of oligodendroglial precursor cells, which results in the
production of
pro-inflammatory cytokines as well as inducible nitric oxide synthase
(iNOS),
and a decrease in myelin protein expression. Within chronic brain
lesions in
MS, HERV-Wenv was detected in microglia / macrophages near
TLR4-positive
oligodendroglial precursor cells. Immunohistochemical detection of
HERV-Wenv
protein in postmortem brain samples of MS patients showed its elevated
levels
only in active lesions in astrocytes and microglia, and the intensity
of
staining correlated with the degree of active demyelination and
inflammation.
Thus, EBV infection and activation of retroviruses are considered as
important
elements in the pathogenesis of MS. Within the framework of the "viral
hypothesis", the most important tasks are the verification of data
indicating the possible etiological role of EBV, the study of the
pathogenetic
mechanisms associated with MSRV/HERV-W at different stages of MS
development,
as well as the identification of immunological and genetic factors
associated
with the defective control of EBV-infected B cells and, as a result,
their
migration and accumulation in the CNS. Thus, EBV infection and
activation of
retroviruses are considered as important factors in the pathogenesis of
MS.
Late EBV infection may be the initiating trigger of the pathological
process
leading to the development of MS years later, and HERV-W / MSRV affect
as
active cofactors of the neuropathogenesis of the MS accompanying the
course of
the disease. The aim of the review
was to consider the
latest evidence of possible mechanisms of the involvement of EBV and
human
endogenous retroviruses in the pathogenesis of multiple sclerosis.
Keywords: multiple
sclerosis, Epstein-Barr virus, human endogenous retroviruses,
immunopathogenesis.
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32-37
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STUDY OF
the influence of a gel former (thickener) type ON THE SORBTION Kinetic
OF
LONG-livING RADIONUCLIDES AND HEAVY METALS BY NATURAL ZELOLITE PASTE
FROM AN
AQUEOUS SOLUTION IN VITRO
Rybachuk V.D.,
Krasnopyorova A.P., Yuhno G.D.
Introduction. The
deterioration of the population health, due to the chemicalization of
many
aspects of life, requires the development and introduction of new
healing
technologies. One of the modern areas of efferent therapy is the oral
administration of sorbents. An alternative to solid dosage forms, in
some acute
cases, is using enterosorbents in the form of paste, but in the
Ukrainian pharmaceutical
market, the range of such medicines has only several positions. The
promising
sources for the creation of such medicines is the natural zeolite. The aim of our study was to investigate the
influence of a gel former (thickener) type on the sorption kinetics of
long-living 90Sr and 137Cs radionuclides and Pb2+
and Hg2+ heavy metals by natural zeolite paste from an
aqueous
solution in vitro. Materials
and methods. As objects for the study we used
experimental pastes containing 25% natural zeolite each and different
gel
formers: 7% silicon dioxide, 3% apple pectin and 0.5% sodium alginate.
As
sorption medium, we used solutions 7.25 mg/l Hg(NO3)2·H2O
and 6.74 mg/l Pb(NO3)2 and radionuclide solutions
90Sr
(1.8 × 107 Bq/dm3) and 137Cs (3.2 × 107 Bq/dm3).
The sorption capacity for heavy metals was investigated by a limited
volume
method at pH = 2 and pH = 6. The concentration of lead was determined
by atomic
absorption spectroscopy (atomic absorption spectrophotometer C-115 PCS)
in a
flame of acetylene-air (λ = 283.3 nm). The concentration of mercury was
determined by the flame atomization method using mercury device PR-115
(λ =
253.7 nm). The sorption capacity of the samples against radionuclides
was
studied by the static sorption method at pH values 2.0, 5.5 and 8.0.
The
radioactivity were measured by a α-β-automaton NRR-610 "Tesla"
radiometer. Concentration of ions and radioactivity of solutions were
controlled after 0.5, 1, 2, 3, 4 and 5
hours of experiment. The equilibrium capacity of sorbents coefficient (Aeq.,
mg/g), the coefficient of sorption (Ks,%) and the
coefficient of
distribution of (Kd, l/g) were calculated for evaluation the
process. Results and
discussion. The process of sorption includes two main stages – fast
and slow. The
first stage is responsible for the process of saturation of
microcrystals by
ions on the surface of the sorbent. The second stage, which indicates
the
complete saturation of sorbent surface by the ions with the subsequent
slow
diffusion ions inside the sorbent. For most of the investigated
objects, the
achievement of the adsorption equilibrium in the heterophasic system
took place
within first 30-60 minutes of the experiment. The sorption activity of
samples
against heavy metals and radionuclides varied widely and depended on a
number
of factors, such as the type of gel formers, pH of the solution, nature
and
physico-chemical properties of the ions (hydration energies, charge and
radius
of the ions). Significant influence on the sorption gave the pH value
of the
solutions. The complex nature of this dependence we explain by the
influence of
the acidity of the solution on the physico-chemical properties and the
structure of the sorbents, as well as on their sorption-active centres.
In
this connection, it can be assumed that
under other equal conditions, the exchange capacity of the studied
sorbents in
the stomach environment will be minimal, and will grow
in the moderately alkaline
environment of different parts of the intestine.
The Kd value of studied
samples against heavy metals allowed us to compare the sorption and
selective
properties of samples and arrange the metal ions in order of decreasing
their
relative affinity to sorbents as Hg2+>Pb2+.
This
difference in selectivity can be explained by the difference in an
electronic
configuration, as well as by a radius and a value of hydration energy
of ions. The
obtained Kd and Ks
of
radionuclides showed
that samples better absorb 137Cs
radionuclide at all pH values. The
sorption characteristics of 90Sr
are much lower, but they increase
sharply with increasing pH values. The highest affinity with respect
to 137Cs
and 90Sr radionuclides
was demonstrated by samples with
silicon dioxide as a gel former.
The greatest activity against all
metals also showed the composition of the paste containing silicon
dioxide as a
gel former. Its sorption coefficient for lead and mercury ions were
93.2-99%
and 95.8% respectively, and for 90Sr and 137Cs
radionuclides were 19-65% and 64-91% respectively.
Conclusions. The influence
of the type of gel formers (thickeners) on the sorption kinetics of
long-living
radionuclides and heavy metals by natural zeolite paste
(clinoptilolite) from
an aqueous solution in vitro was studied. The best results samples with
silicon
dioxide have demonstrated. The obtained results will be taken into
account in
the further development of medicines with natural zeolite
(clinoptilolite) in
the paste form.
Keywords: natural
zeolite, paste, sorbtion, radionuclides, heavy metals, gelling agents
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38-44
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INVESTIGATION OF THE PHARMACO-TECHNOLOGICAL PROPERTIES OF SOLID
DISPERSIONS OF THIOCTIC ACID, OBTAINED BY MICRONIZATION
Kovalevska I.V, Ruban O.A.
Introduction. Thioctic acid is used in the treatment of
diseases that are characterized by lack of mitochondrial activity, which is
responsible for the formation of free radicals. Widespread use of thioctic acid
is due to the chemical structure. The thioctic acid exhibits biological
activity in both hydrophilic and hydrophobic environments. Thioctic acid is an
enzyme cofactor and a powerful antioxidant, it regulates the transcription of
numerous genes, participates in regulation of glucose and lipid metabolism,
increases insulin sensitivity, and forms complexes with heavy metals. Thioctic
acid has a high pharmacological potential, which is confirmed by the evidence
base of clinical trials. An analysis of the literature on the oral use of
thioctic acid indicates that solid dosage forms can be used for long-term
therapy. This route of administration is limited by factors such as reduced
solubility in acidic environments and enzymatic degradation. For this reason,
the search for various compositions of auxiliary substances and methods of
obtaining drugs is an urgent task of pharmaceutical technology. Material & methods. Objects of
study were solid dispersions of thioctic acid (SDTA) on the basis of cellulose
derivatives: microcrystalline (MCC), HPMC (hydroxypropyl methylcellulose) and
polyvinylpyrrolidone (PVP) as compared to thioctic acid (TA). The samples were
made by solid phase method using micronization in a laboratory shredder at a
ratio of 1: 1. Pharmacological and technological parameters were determined
according to generally accepted methods. Results
& discussion. In appearance the resulting mixtures had lemon color,
without inclusions and the formation of conglomerates, with homogeneous sized
particles According to the pharmaco-technological studies, the samples do not
have a satisfactory flowability. The values of the Carr index and the ratio of
Hausner make it possible to conclude that there is a large force of cohesion
between the particles, a significant aeration of the material. As can be seen
from the data presented in the table, micronization in the medium of MCC, PVP
and HPMC has led to a change in the density of stacking, which is
characteristic of powders with an anisodiametric form of particles, but the
strength of the internal friction coefficient has practically not changed, as
evidenced by the indicators of the natural slope. The value of porosity
suggests a significant degree of the Van der Waals forces action between the
particles of the SD. All samples of solid dispersions can be attributed to
fragile materials: BW was 5.57 kgf / mm2. When stored in a static
state, there was a partial agglomeration. The results show that all samples of
solid dispersions are well moistened with purified water, as opposed to a
sample of tioctic acid. An analysis of the marginal wetting angle indicates
that the surfaces of samples of solid dispersions are hydrophilic. According to the microscopic analysis it was
established that the influence of external forces has changed the form of the
thioctic acid: from the plate with the factor of the form 0,85 to the uncertain
form. In samples with microcrystalline cellulose and hydroxypropyl
methylcellulose there is a mixture of crushed thioctic acid crystals and
carrier. The form factor has dropped to 0.45. The investigation of the
dissolution of the obtained solid dispersions showed that the addition of MCC
to thioctic acid even reduces the amount of matter passing into the solution,
as opposed to solid dispersions with PVP and HPMC (24% and 37% respectively).
The difference in the values of dissolution can be due to both the nature of
chemical bonds, and the nature of electrostatic attraction, due to the polarity
and the emergence of hydrogen bridges. The investigation of the dissolution of
the obtained solid dispersions showed that the addition of microcrystalline
cellulose to thioctic acid even reduces the amount of matter passing into the
solution, as opposed to solid dispersions with PVP and HPMC. The difference in
the values of dissolution can be due to both the nature of chemical bonds, and
the nature of electrostatic attraction, due to the polarity and the emergence
of hydrogen bridges. Conclusion.
Thus, the results indicate an increase in the dissolution of thioctic acid in
the solid dispersion with PVP in 2.6 times, with HPMC in 1.3 times, which may
be the basis for research on the development of solid dosage forms of thioctic
acid.
Keywords: Thioctic
acid, solid dispersions, pharmaceutical technology, micronization
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45-51
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