Wound-healing effect of polyguanidine-based hydrogel

This article present the evaluation of polyhexamethyleneguanidine hydrochloride hydrogel influence on the course of wound healing processes. Synthesis of hydrogel is based on the interaction of amino-end groups of the polymer with carbonyl compounds. The presence of significant biocidal properties of the gel-forming polymer is allowed to consider the hydrogel as a wound healing agent. Since most wound healing agents for external use are made in the form of gels, ointments, polymer-based, it was decided to use the wound healing agent "Levomekol", a gel which consists of poly (ethylene oxide) as a comparison drug. So, in terms of linear skin-muscle wound we established the pronounced wound-healing effect of a polyhexamethyleneguanidine hydrochloride hydrogel. The results of pathomorphological studies revealed that in animals of the experimental "hydrogel" group on the eighth day of the experiment, the wound was undergoing a process of rejection of the scab, the presence of mature granulation tissue and no exudate was also observed. In the comparison group, the healing process was more slow, on the eighth day of the experiment in the animal group we observed the presence of fluid under the eschar, and lower amount of mature granulation tissue. Tensiometry of the scar has shown that the strength of scar rupture in the "hydrogel" group requires 65 % more force compared to the control group, while in the group of comparison this parameter made only 48 %

Acute Toxicity of Hydrogel Polyhexamethylene Guanidine Hydrochloride

Background. Previously, we have shown that the polyhexamethylene guanidine hydrochloride hydrogel exhibits a pronounced wound healing. At the same time, no studies of the toxic effect of the hydrogel on animals have been conducted. Aim of the research. In the framework of this work, the acute toxicity of the hydrogel polyhexamethylene guanidine hydrochloride was studied in laboratory animals with intragastric administration. Materials and methods. The polyhexamethylene guanidine hydrochloride hydrogel was obtained by crosslinking the amino end groups with formaldehyde. An acute toxicity study was carried out (P 1.2.3156-13, GOST 32644-2014 and the Guidelines for conducting preclinical studies of drugs) in an experiment on outbred mice with a single addition of the test substance in different doses (1000, 3000, 5000, 8000 mg/kg) with fixing indicators (appearance, behavior, condition of the body hair coat, water and food consumption, excretion, body weight and its growth) during 14 days. After the animals were withdrawn from the experiment, autopsy, macroscopic evaluation and weighing of the internal organs were performed. The results showed that with the introduction of the test substance into the animal organism, death during the observation period (14 days) did not occur. It was not possible to determine the semi-lethal dose for the test compound. Conclusion. The conducted studies allow us to conclude that this substance is practically non-toxic and can be classified as hazard class V. Further research will be directed to the formation of hydrogel compositions with medicinal substances

WOUND HEALING EFFECT OF POLYHEXAMETHYLENE GUANIDINE HYDROCHLORIDE HYDROGELAT BURNS

This article considers the wound-healing effect of a hydrogel based on polyhexamethyleneguanidine hydrochloride under conditions of thermal shock modeling. The presence of gelling properties in combination with the high biocidal activity of polyguanidins opens the prospect of obtaining an effective single-component external agent, which is very important for antimicrobial chemotherapy of wounds and burns, as in their treatment there is a high probability of infecting the wound with microorganisms causing various infectious diseases. Previously, we developed a method for the preparation of a hydrogel based on polyhexamethyleneguanidine hydrochloride, which involves the cross-linking of the amino-end groups of the branched polymer with formaldehyde, resulting in a cross-linked polymer, which is a lump-like mass. The mechanical treatment of the hydrogel makes it possible to give the material an ointment form that is convenient for application to the skin. An experiment on the evaluation of the wound healing action of hydrogel was carried out under the conditions of modeling a thermal burn. The comparative preparation was multicomponent gel "Levomekol", in which polyethylene oxide was used as the basis. It was established that the hydrogel activates the growth of antioxidants and leukocytes in the blood of animals in dynamics on the 10th, 17th and 24th day of the experiment, amounting to 56.4 %, 33.8 % and 20.9 %, and of leukocytes - 27.7 %, 19.6 %; 6,2 % in relation to the norm. The method of contrast radiography of penetrating wounds showed that the daily reduction in the wound area is most pronounced in the hydrogel group, which indicates a pronounced reparative effect

Репаративное действие гидрогеля полигексаметиленгуанидин гидрохлорида

Polyguanidines are characterized by pronounced antimicrobial activity and are widely used as the main active substance of disinfectants. Polymers of this class possess the property of gel formation, which, together with biological activity, opens the prospect of obtaining an effective single-component agent or basis for an external preparation for the therapy of skin lesions. Earlier, we developed a method for the production of a hydrogel based on polyhexamethyleneguanidine hydrochloride, which involves the cross-linking of the terminal amino groups of the branched polymer with formaldehyde.The purpose of the study was to observe the effect of hydrogel polyhexamethyleneguanidine hydrochloride on the progression of wound healing.Materials and methods. An experiment on the evaluation of the wound healing action of hydrogel was carried out under conditions simulating a linear cutaneous wound, a muscular wound, and a thermal burn. The comparative drug was the pharmacopoeian drug Levomecol.Results. It has been established that hydrogel has a pronounced wound healing effect, as evidenced by the results of ruminant thoracic anatomy and pathomorphology of the sections, which shows accelerated ripening of granulation tissue and scar formation. By the method of vulnografiya it was shown that the daily decrease in wound area is most pronounced in the hydrogel group, which also indicates a pronounced reparative effect. It was determined that the hydrogel activates the growth of antioxidatic activity and leukocytes in the blood of animals in dynamics on the 10th, 17th and 24th day of the experiment, amounting to 56, 34 and 21%, and of leukocytes – 32, 30, 10% in relation to the intact animals.Conclusion. Thus, on the model of a linear cutaneous wound, a muscular wound, and a thermal burn, the healing effect of the hydrogel PGMGh/f is established, as evidenced by the results of the early exercise, vulnografiya and pathomorphological studies. It is noted that the hydrogel PGMG h/f has an effect on the content of antioxidants and leukocytes in the blood, contributing to the normalization of their quantity.Полигуанидины характеризуются выраженной антимикробной активностью и находят широкое применение в качестве основного действующего вещества в составе дезинфицирующих средств. Полимеры этого класса обладают свойством гелеобразования, что в совокупности с биологической активностью открывает перспективу получения эффективного однокомпонентного средства или основы препарата наружного применения для терапии повреждений кожных покровов. Ранее нами был разработан способ получения гидрогеля на основе полигексаметиленгуанидин гидрохлорида, заключающийся в сшивании концевых аминогрупп разветвленного полимера формальдегидом.Целью работы явилось изучение влияния гидрогеля полигексаметиленгуанидин гидрохлорида на течение раневого процесса.Материалы и методы. Эксперимент по оценке ранозаживляющего действия гидрогеля проводился в условиях моделирования линейной кожно-мышечной раны и термического ожога. В качестве сравнения использовался фармакопейный препарат «Левомеколь».Результаты. Установлено, что гидрогель обладал выраженным ранозаживляющим действием на модели линейной раны, о чем свидетельствовали результаты ранотензометрии рубца и патоморфологии срезов, показавшие ускоренное созревание грануляционной ткани и формирование рубца. Методом вульнографии на модели термического ожога показано, что суточное уменьшение площади раны в наибольшей степени эксплицировано у опытной группы 1 (гидрогель), что также свидетельствовало о его выраженном репаративном действии. Определено, что при ожоге наблюдались резкое уменьшение суммарной антиоксидантной активности сыворотки крови и нарастание количества лейкоцитов. В динамике на 10-, 17- и 24-е сут эксперимента уменьшение первого показателя составило 56, 34 и 21%, а увеличение второго показателя – соответственно на 32, 30 и 10% по отношению к интактным животным. Применение гидрогеля более эффективно, чем препарата сравнения, способствовало нормализации данных показателей.Заключение. Таким образом, на моделях линейной кожно-мышечной раны и термического ожога установлено выраженное ранозаживляющее действие гидрогеля, о чем свидетельствовали результаты ранотензометрии, вульнографии патоморфологических исследований. Более высокий ранозаживляющий эффект гидрогеля, по-видимому, связан с увеличением суммарной антиоксидантной активности и более выраженным восстановлением количества лейкоцитов в крови

Charge separation relative to the reaction plane in Pb-Pb collisions at sNN=2.76\sqrt{s_{\rm NN}}= 2.76 TeV

Measurements of charge dependent azimuthal correlations with the ALICE detector at the LHC are reported for Pb-Pb collisions at $\sqrt{s_{\rm NN}} = 2.76$ TeV. Two- and three-particle charge-dependent azimuthal correlations in the pseudo-rapidity range $|\eta| < 0.8$ are presented as a function of the collision centrality, particle separation in pseudo-rapidity, and transverse momentum. A clear signal compatible with a charge-dependent separation relative to the reaction plane is observed, which shows little or no collision energy dependence when compared to measurements at RHIC energies. This provides a new insight for understanding the nature of the charge dependent azimuthal correlations observed at RHIC and LHC energies.Comment: 12 pages, 3 captioned figures, authors from page 2 to 6, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/286

Transverse sphericity of primary charged particles in minimum bias proton-proton collisions at s=0.9\sqrt{s}=0.9, 2.76 and 7 TeV

Measurements of the sphericity of primary charged particles in minimum bias proton--proton collisions at $\sqrt{s}=0.9$, 2.76 and 7 TeV with the ALICE detector at the LHC are presented. The observable is linearized to be collinear safe and is measured in the plane perpendicular to the beam direction using primary charged tracks with $p_{\rm T}\geq0.5$ GeV/c in $|\eta|\leq0.8$. The mean sphericity as a function of the charged particle multiplicity at mid-rapidity ($N_{\rm ch}$) is reported for events with different $p_{\rm T}$ scales ("soft" and "hard") defined by the transverse momentum of the leading particle. In addition, the mean charged particle transverse momentum versus multiplicity is presented for the different event classes, and the sphericity distributions in bins of multiplicity are presented. The data are compared with calculations of standard Monte Carlo event generators. The transverse sphericity is found to grow with multiplicity at all collision energies, with a steeper rise at low $N_{\rm ch}$, whereas the event generators show the opposite tendency. The combined study of the sphericity and the mean $p_{\rm T}$ with multiplicity indicates that most of the tested event generators produce events with higher multiplicity by generating more back-to-back jets resulting in decreased sphericity (and isotropy). The PYTHIA6 generator with tune PERUGIA-2011 exhibits a noticeable improvement in describing the data, compared to the other tested generators.Comment: 21 pages, 9 captioned figures, 3 tables, authors from page 16, published version, figures from http://aliceinfo.cern.ch/ArtSubmission/node/308

Effective Rheology of Bubbles Moving in a Capillary Tube

We calculate the average volumetric flux versus pressure drop of bubbles moving in a single capillary tube with varying diameter, finding a square-root relation from mapping the flow equations onto that of a driven overdamped pendulum. The calculation is based on a derivation of the equation of motion of a bubble train from considering the capillary forces and the entropy production associated with the viscous flow. We also calculate the configurational probability of the positions of the bubbles.Comment: 4 pages, 1 figur

Centrality dependence of charged particle production at large transverse momentum in Pb-Pb collisions at sNN=2.76\sqrt{s_{\rm{NN}}} = 2.76 TeV

The inclusive transverse momentum ($p_{\rm T}$) distributions of primary charged particles are measured in the pseudo-rapidity range $|\eta|<0.8$ as a function of event centrality in Pb-Pb collisions at $\sqrt{s_{\rm{NN}}}=2.76$ TeV with ALICE at the LHC. The data are presented in the $p_{\rm T}$ range $0.15<p_{\rm T}<50$ GeV/$c$ for nine centrality intervals from 70-80% to 0-5%. The Pb-Pb spectra are presented in terms of the nuclear modification factor $R_{\rm{AA}}$ using a pp reference spectrum measured at the same collision energy. We observe that the suppression of high-$p_{\rm T}$ particles strongly depends on event centrality. In central collisions (0-5%) the yield is most suppressed with $R_{\rm{AA}}\approx0.13$ at $p_{\rm T}=6$-7 GeV/$c$. Above $p_{\rm T}=7$ GeV/$c$, there is a significant rise in the nuclear modification factor, which reaches $R_{\rm{AA}} \approx0.4$ for $p_{\rm T}>30$ GeV/$c$. In peripheral collisions (70-80%), the suppression is weaker with $R_{\rm{AA}} \approx 0.7$ almost independently of $p_{\rm T}$. The measured nuclear modification factors are compared to other measurements and model calculations.Comment: 17 pages, 4 captioned figures, 2 tables, authors from page 12, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/284

Elliptic flow of charged particles in Pb-Pb collisions at 2.76 TeV

We report the first measurement of charged particle elliptic flow in Pb-Pb collisions at 2.76 TeV with the ALICE detector at the CERN Large Hadron Collider. The measurement is performed in the central pseudorapidity region (|$\eta$|<0.8) and transverse momentum range 0.2< $p_{\rm T}$< 5.0 GeV/$c$. The elliptic flow signal v$_2$, measured using the 4-particle correlation method, averaged over transverse momentum and pseudorapidity is 0.087 $\pm$ 0.002 (stat) $\pm$ 0.004 (syst) in the 40-50% centrality class. The differential elliptic flow v$_2(p_{\rm T})$ reaches a maximum of 0.2 near $p_{\rm T}$ = 3 GeV/$c$. Compared to RHIC Au-Au collisions at 200 GeV, the elliptic flow increases by about 30%. Some hydrodynamic model predictions which include viscous corrections are in agreement with the observed increase.Comment: 10 pages, 4 captioned figures, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/389