Source: https://russianpatents.com/patent/255/2554219.html
Timestamp: 2019-04-19 01:23:45+00:00

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SUBSTANCE: group of inventions relates to medicine, namely to dermatology and mycology, and can be applied in the treatment of skin and its appendages. A pharmaceutical composition for external application contains nanoparticles for the laser thermotherapy of infectious affections of the skin and its appendages. The nanoparticles are characterised by, at least, one localised surface Plasmon resonance in the range of a wavelength from 400 to 1100 nm. The nanoparticles are dispersed in a physiologically acceptable carrier, which is characterised by the absence of the absorption or weak absorption and/or weak dispersion of light radiation in the said range of wavelengths and possessing biocidal properties. The pharmaceutical composition is applied on an affected area and irradiated by laser radiation with a wavelength close to the wavelength of the localised surface Plasmon resonance of the nanoparticles, contained in the composition, or equal to it. The irradiation is continued until the desirable temperature of heating of the said area is achieved.
EFFECT: group of inventions ensures an increased treatment efficiency, reduction of a risk of development of side effects, reduction of the number of recurrences due to the application of the pharmaceutical composition, capable of absorbing energy of the light radiation and transforming it into heat energy with the achievement of the specified temperature with laser irradiation at the specified wavelength with the lower intensity of laser radiation and possessing biocidal properties.
The invention relates to medicine, namely to dermatology and Mycology, in particular to methods of treatment of the skin and its appendages, including hair and nails with fungal lesions, viral or bacterial origin, including fungal infections and other infectious diseases, using laser thermotherapy and to means for the implementation of their treatment.
Infectious lesions of the skin and its appendages, including onychomycosis and dermatomycoses are among the most unpleasant diseases, difficult to treat and can lead to serious violations of both the physical and psychological state of the person. The occurrence of these diseases is very high, especially among persons of middle and older age. According to statistics, onychomycosis suffer 2.6% of the population under the age of 18 years, 36% aged 25-60 years, and for people over 75 years of age, this figure rises to 90%.
A traditional method of treatment of infectious lesions of the skin and its appendages, in particular of onychomycosis is the medical approach. It is based on the use of pharmaceutical drugs for systemic or local action. In the case of onychomycosis to improve the efficiency of medical treatment may be necessary prior complete or partial removal of the nail plate and surgical�and chemical means. This procedure is quite painful and can lead to loss of the nail plate, the change in shape and/or ingrown nail.
It is known that nanoparticles of gold, silver and copper have a high toxicity against bacteria, viruses and other pathogenic organisms (Zhou Y., Kong Y., Kundu S., Cirillo, J. D., Liang H. "Antibacterial activities of gold and silver nanoparticles against Escherichia coli and bacillus Calmette-Guérin". J. nanobiotechnology is, 2012, V. 10, p. 19; Ramyadevi J., Jeyasubramanian K., Marikani A., Rajakumar g, Rahuman, A. A. "Synthesis and antimicrobial activity of copper nanoparticles". Mater. Lett., 2012, V. 71, P. 114). Mostly it is a property inherent to nanoparticles of silver and copper.
From the point of view of creation of drugs with high biocidal activity, the use of silver nanoparticles is preferred because they are more stable to oxidation by atmospheric oxygen compared with nanoparticles of copper.
For example, a method of treating skin diseases (US, 2003/0194444, A1) by treating skin ointment or gel products containing nanoparticles of silver or its compounds, such as oxides or halides.
Known agent in the form of ointments for the treatment and prevention of fungal diseases of the skin (RU, 2428184, C1), containing as antifungal agents, 0.9-1.1 wt.% bifonazole, 6-10 wt.% Zola silver nanoparticles and 6-10 wt.% Zola nanoparticles of copper, and as the basis - a mixture of �of polietilenoksidov different molecular weights (400, 1500, 2000 and 4000) and water. The presence of nanoparticles of silver and copper leads to an increase in the fungicidal activity of the specified means and reduce side effects.
However, medical methods of treatment of infectious lesions of the skin and its appendages are characterized by long duration and high cost, high probability of relapse, and high toxicity of the drugs used and serious side effects associated with liver damage and kidney of a patient after oral administration of drugs.
Therefore, the development of alternative methods of treatment, devoid of the above disadvantages, is a very important task of dermatology.
It is known that the treatment of the affected area by the laser radiation at certain wavelengths can lead to cell death of pathogenic organism by thermal or photochemical mechanism. The main condition for the application of laser therapy is the presence in the cells of the pathogenic organism of endogenous or exogenous (added) substances capable of absorbing optical radiation with a wavelength in a certain range and to transform it into another form of energy, e.g. thermal energy. This leads to local heating of the cell above physiological temperatures and of her death. Hereinafter, the substances capable p�to glomate radiation and transform it into thermal energy, will be called thermoinsulation. To ensure the most efficient heat necessary to carry out the irradiation of the affected area radiation with a wavelength coinciding with the absorption maximum of thermogenerator.
A method of treating fungal infections and other infectious lesions of nails and skin (US 6090788, A1), based on the presence in a cell of a pathogenic organism of endogenous molecules or exogenous thermogenerator. The affected area is irradiated with light at least one wavelength coincides with the absorption maximum of thermogenerator. Such exposure leads to heating and cell death of pathogenic organism. As exogenous thermogenerator use acceptable for introduction into the cells of the pathogen compounds that contribute locally or administered through the circulatory system of a patient, such as pigments and dyes specifically binding to a pathogenic cell. However, the absorption cross-sections used connections is very small. Therefore, to ensure the necessary heating of the affected area must be used when irradiated by high power lasers that can burn healthy tissue.
The purpose of creating the present invention was to develop tools for local laser thermotherapy, including in GUI mode�starmie, areas of the skin and its appendages, including hair and nails, having an infection of a fungal, viral and bacterial origin, including fungal infections and other diseases, and development of methods of laser thermotherapy, providing increase of efficiency of treatment of these infectious diseases, reduction of terms of treatment, reducing the risk of side effects, decrease the number of recurrences.
When creating the present invention was tasked with developing a method local laser thermotherapy, which provides heating of the affected area to a certain desired temperature, in particular in conditions of hyperthermia is to a temperature that ensures the destruction of the source of infection, by use of funds external use, eliminating the need for their introduction into the circulatory system of the body, and the use of laser radiation, harmless to human body mode.
For the task was the analysis of known means, which under the action of laser radiation is provided by the increase of temperature. This analysis showed that the nanoparticles of gold, silver, copper and composite structure on the basis of these metals are able to absorb radiation with a certain wavelength due to the presence of the effect of localized surface PL�Smolnogo resonance (LPR or LSPR - Localized Surface Plasmon Resonance). Thus, in comparison with any dyes, these particles have 4-5 orders of magnitude larger values absorption cross-sections (Jain R. K., Lee K. S., El-Sayed I. H., El-Sayed M. A., "Calculated Absorption and Scattering Properties of Gold Nanoparticles of Different Size, Shape, and Composition: Applications in Biological Imaging and Biomedicine". J. Phys. Chem. V., 2006, V. 110, No. 14, P. 7238). As a result of local heating of the nanoparticles under the action of laser radiation can reach several hundred degrees.
Thus, the use of metal nanoparticles will allow for heating of the affected area of the skin or its appendages to the temperature required for the cell death of pathogenic organism, at a much lower laser intensity, which should reduce the likelihood of damage to healthy tissue of the patient.
The position of the maximum LPR metallic nanoparticles depends on the nature of the metal of which they consist, and from their size and shape.
For example, for spherical gold particles with increase in their size from 10 nm to 100 nm max LPR is shifted from the wavelength of 500 nm at a wavelength of 540 nm, while for spherical silver particles with a wavelength of 400 nm at a wavelength of 430 nm (Dykman L. A., Bogatyrev V. A., Shchyogolev S. Yu., Crispbread N. G. "Gold nanoparticles: synthesis, properties for biomedical application". M.: Nauka, 2008, p. 319; Suzdalev I. P. "Nanotechnology: physical chemistry of nanoclusters, nanostructures and nanom�materials". M: Komkniga, 2005, p. 592).
In addition, for particles of nonspherical shape - sterjnevye, elliptical, prismatic and other forms, there are usually several peaks LPR (O. V. Dement'eva, V. M. Rudoy "Colloid-chemical synthesis of new nanostructures based on silver with a given position of the localized surface plasmon resonance". The colloid. Phys., 2011, vol. 73, No. 6, p. 726). For example, for sterzhnevykh particles is characterized by two peaks corresponding to the transverse and longitudinal LPR. The peak longitudinal LPR is shifted to the long wavelength region, and this shift is greater, the greater the ratio of the length of the particles to their diameter.
For hollow nanoparticles of alloys of gold, silver, copper or composite nanoparticles (hereinafter ELF, composite nanoparticles - CNP) with the structure of "core-shell", in which the shell consists of the above metals or their alloys, and the core are made of hard metal, for example a dielectric or semiconductor, it is possible to vary the position LPR in the visible and near IR region due to the advances in the manufacture of corresponding size and/or shape of the nucleus and the thickness of the shell (S. J. Oldenburg, R. D. Averitt, S. L. Westcott, Halas N. J. "Nanoengeneering of optical resonances". Chem. Phys. Lett., 1998, V. 288. P. 243).
For anisotropic ELF with spheroidal nucleus, for example, oxide or (HYDR)oxide of iron, is characterized by the presence of two absorption bands in the visible and near IR about�'asti corresponding to transverse and longitudinal LPR respectively (Wang N., D. W. Brandl, F. Le, P. Nordlander, N. J. Halas "Nanorice: A Hybrid Plasmonic Nanostructure". Nano Lett., 2006, V. 6. P. 827). Their position depends on the thickness of the shell, the kernel size and the degree of ellipticity (the ratio of large radius to a small kernel). Ceteris paribus decrease in the thickness of the metallic shell leads to a shift of both peaks LPR in the long wavelength region.
Therefore, by varying the size and/or shape of the core and the shell thickness of the composite nanoparticles can customize LPR nanoparticles at a predetermined wavelength in the visible or near infrared range of the spectrum. For example, "setting" LPR can be done by providing in the composite nanoparticles of the ratio of core diameter to the shell thickness corresponding to the desired position LPR in absorption spectrum, or by using as the nuclei of the particles of the same size and varying only the thickness of the shell composite nanoparticles. It is possible to synthesize a set of ELF, on absorbing characteristic for each type of nanoparticles wavelength in a wide spectral range. Exposure to such nanoparticles laser radiation at a wavelength corresponding to a characteristic wavelength LPR and selected in the range of maximum transparency of biological tissue, can be ensured maximum absorbed�e light energy nanoparticles leading to heating of the nanoparticles. These particles when placed in a physiologically acceptable medium can be delivered to the area of the skin or its appendages, with lesions that require laser thermotherapy, including the effect of hyperthermia, necessary for the destruction of pathogenic cells.
One of the objects of the present invention is a pharmaceutical composition for external use laser thermotherapy of the skin and its appendages with infectious lesions containing nanoparticles, characterized by at least one of the localized surface plasmon resonance in the wavelength range from 400 to 1100 nm, dispersed in a physiologically acceptable carrier, characterized by the absence of absorption or poor absorption and/or weak scattering of light radiation in a specified wavelength range, and with biocidal properties.
It is preferable that the pharmaceutical composition contained nanoparticles, characterized by at least one of the localized surface plasmon resonance in the wavelength range from 600 to 1100 nm.
Thus, according to the invention, it is possible that these nanoparticles consisted of spherical nanoparticles consisting of metals selected from the group comprising gold, silver, copper and alloys of these IU�allow.
In addition, according to the invention, it is possible that these nanoparticles presented an anisotropic nanoparticles consisting of metals selected from the group comprising gold, silver, copper and alloys of these metals. In addition, according to the invention, it is possible that these nanoparticles was a hollow nanoparticles composed of metals selected from the group comprising gold, silver, copper and alloys of these metals. In addition, according to the invention, it is possible that these nanoparticles consisted of composite nanoparticles with the structure of the core-shell in which the core is made of a dielectric or semiconductor material, and the shell is made of metal selected from the group comprising gold, silver, copper and their alloys.
Thus, according to the invention, these composite nanoparticles can be spherical in form.
Thus, according to the invention, it is possible that the core of these composite nanoparticles were made of solid silicon dioxide.
Thus, according to the invention, it is possible that the core of these composite nanoparticles were made of a material with a porous structure.
Thus, according to the invention, it is possible that the core of these composite nanoparticles were made of mesoporous silica.
Furthermore, according invented�Yu, it is possible that these composite nanoparticles had an anisotropic shape.
The core of these composite nanoparticles can be made of oxide or (HYDR)oxide of iron.
Thus, according to the invention, it is possible that the pharmaceutical composition according to the invention contain nanoparticles in a concentration of from 0.0001 to 5.0 wt.% based on the content of metal or metal alloy, preferably in a concentration of from 0.005 to 0.10 wt.% based on the content of the metal or alloy of metals.
In addition, according to the invention, it is possible that this pharmaceutical composition was made in the form of a spray is water-based.
In addition, according to the invention, it is possible that this pharmaceutical composition was made in the form of an ointment or a gel based on hydrophilic physiologically acceptable carrier.
In addition, according to the invention, it is possible that the specified hydrophilic physiologically acceptable carrier contained hydrophilic biocompatible polymer.
In addition, according to the invention, it is possible that the specified hydrophilic biocompatible polymer was preferably selected from the group consisting of: starch, gelatin, collagen, cellulose ethers, carbopols, polyvinylpyrrolidone, polyvinyl alcohol, polyethylene oxide.
In addition, according to the invention may h�Oba in the specified pharmaceutical composition of nanoparticles were introduced in the form of colloidal solution.
In addition, according to the invention, it is possible that in the specified pharmaceutical composition of nanoparticles were introduced in powder form. Thus, according to the invention, the powder can be obtained by freeze drying of colloidal solution containing the nanoparticles.
In addition, according to the invention, it is possible that this pharmaceutical composition was adapted for use in the laser thermotherapy of the skin and its appendages, with the defeat of fungal, viral or bacterial origin, and thus also contain a means of having, respectively, antifungal, antiviral and antibacterial action.
Thus, according to the invention, it is possible that this pharmaceutical composition was adapted for use in the laser thermotherapy of the skin and its appendages, with the defeat of a fungal nature, and thus contained a remedy antifungal activity selected from the group of antifungal drugs local action, consisting of clotrimazole, acteria, lamizila, loteria and other drugs of similar effect.
Thus, according to the invention, it is possible that this pharmaceutical composition contains additionally a means keratolytic action. Wherein the means keratolytic action �can be selected from the group consisting of urea and salicylic acid.
Thus, according to the invention, it is possible that this pharmaceutical composition was adapted for use in the laser thermotherapy of the skin and its appendages, with the defeat of viral nature, and it contains the antiviral agent of the action selected from the group of antiviral drugs, consisting of imidazole derivatives, triazole and allilamina and other drugs of similar effect.
Thus, according to the invention, it is possible that this pharmaceutical composition was adapted for use in the laser thermotherapy of the skin and its appendages, with the defeat of bacterial origin, and contain a means of antibacterial action selected from the group of antibacterial drugs operation, consisting of imidazole derivatives, triazole and allilamina and other drugs of similar effect.
Thus, according to the invention, it is possible that in the specified pharmaceutical composition tools above antifungal, antiviral or antibacterial action, or mixtures thereof were placed in a mesoporous core composite nanoparticles having a structure of core - shell, and the core was made of a dielectric or semiconductor mesoporous material and�hidden by a shell of metal, selected from the group including gold, silver, copper and their alloys.
In addition, according to the invention, it is possible that these funds antifungal, antiviral, antibacterial, keratolytic action, or mixtures thereof were placed in a specified hydrophilic physiologically acceptable medium.
Another object of the present invention is a method of laser thermotherapy of the skin and its appendages, with the defeat of infectious nature, in which the area of the skin or its appendages, with the lesion, causing a pharmaceutical composition according to the invention, in the above-described embodiments containing nanoparticles, characterized by at least one of the localized surface plasmon resonance in the wavelength range from 400 to 1100 nm, dispersed in a physiologically acceptable carrier, characterized by the absence of absorption or poor absorption and/or weak scattering of light radiation in a specified wavelength range, and thus having biocidal properties, and then the area of the skin or its appendages, processed the specified pharmaceutical composition is subjected to laser irradiation, at least one wavelength close to the wavelength of the localized surface plasmon resonance of the nanoparticles or equal to DOS�izheniya the desired temperature of heating of the region specified.
Thus, according to the invention, as the source of laser radiation can be used in continuous or pulsed laser, the wavelength of the generation which is in the range of wavelengths from 400 to 1100 nm, preferably, in the wavelength range from 600 to 1100 nm.
Thus, according to the invention, it is possible to use way laser thermotherapy in the mode of local hyperthermia of the skin and its appendages, with the defeat of fungal, viral or bacterial nature, with the use of the pharmaceutical composition according to any embodiment described above according to the invention by heating the affected area to temperatures exceeding physiologically acceptable to the pathogenic cells, under the influence of laser radiation at a wavelength close to the wavelength of the localized surface plasmon resonance of the nanoparticles or equal to it.
Fig.3 - absorption spectrum of the pharmaceutical compositions according to the invention, made in the form of a colloidal solution (Hydrosol) containing anisotropic composite nanoparticles having a core with a length of 200 nm and diameter D=50 nm from the (HYDR)oxide iron (FeOOH) and the shell thickness H=5 nm of silver, presented in the form of the dependence of optical density of the composition of the wavelength of irradiation (curve 3).
While these examples are not exhaustive, does not limit the possibilities of implementing and using the invention, without departing from the scope of the claims.
Method laser thermotherapy of the skin and its appendages, with the defeat of fungal, viral or bacterial nature, including the holding of local hyperthermia is carried out using a pharmaceutical composition according to the invention.
Pharmaceutical composition external use, according to the invention comprises nanoparticles, characterized by at least one of the localized surface plasmon resonance in the wavelength range from 400 to 1100 nm, preferred�thainee, in the wavelength range from 600 to 1100 nm, dispersed in a physiologically acceptable carrier, characterized by the absence of absorption or poor absorption and/or weak scattering of light radiation in a specified wavelength range. The presence in the pharmaceutical compositions according to the invention the nanoparticles are able to effectively absorb radiation with a predetermined wavelength corresponding to the wavelength of their localized surface plasmon resonance, and to transform it into thermal energy, which provides heating of the nanoparticles and a physiologically acceptable carrier in which they are located, and areas of the skin and its appendages in contact with the pharmaceutical composition, for example, providing heating the affected area above physiological temperatures and cell death of pathogenic organism. Due to the fact that, according to the invention, the nanoparticles or their outer shells are composed of metals selected from the group comprising gold, silver, copper and alloys of these metals, pharmaceutical composition according to the invention also have biocidal properties, which provides biocidal treatment of the entire area exposed.
According to the invention, these nanoparticles can be solid, spherical, anisotropic solid, or hollow, or may be a composite� nanoparticles with the structure of core-shell, in which the core is made of a dielectric or semiconductor material, and the shell is made of metal selected from the group comprising gold, silver, copper and their alloys. This composite nanoparticles can be spherical with a core of solid silicon dioxide or a core of a material with a porous structure, such as mesoporous silica, or may have an anisotropic shape with the nucleus, for example, oxide or (HYDR)oxide of iron. The selection of the type, shape and size of the nanoparticles, the ratio of the dimensions of core and shell composite nanoparticles provides a localized surface plasmon resonance of the nanoparticles at a given wavelength of radiation, the choice of the concentration of nanoparticles in the pharmaceutical composition according to the invention and the parameters of laser irradiation provides heating of the specified song to the specified temperature. When the desired type, shape and size of nanoparticles, and the size ratio of core and shell composite nanoparticles can be achieved in the manufacturing process by using known technologies.
As described above, the nanoparticles may be prepared by colloidal chemical synthesis, e.g. in the form of colloidal solutions - hydrosols and can be administered in pharmaceutical compositions in the form of colloidal solution (Hydrosol) or in �IDA powder, for example, obtained by freeze drying of colloidal solution containing the nanoparticles.
To create pharmaceutical compositions according to the invention can be used in different ways. For example, a colloidal solution containing nanoparticles one of the above types, can be mixed with pre-cooked pharmaceutically acceptable carrier in a certain mass (volume) ratio. Or components pharmaceutically acceptable carrier, such as ointment bases, can be entered directly in the colloidal solution of nanoparticles. Or lyophilized nanoparticles in powder form can be added to a pharmaceutically acceptable carrier, e.g. in an ointment base, including immediately prior to use of the pharmaceutical composition.
In the way that laser thermotherapy according to the invention it is expedient to use the pharmaceutical composition according to the invention with a content of nanoparticles in a concentration of from 0.0001 to 5.0 wt.% based on the content of metal or metal alloy, preferably in a concentration of from 0.005 to 0.10 wt.% based on the content of the metal or alloy of metals. The specified concentration of the nanoparticles provides the required degree of absorption of light energy by the nanoparticles.
According to the invention, the pharmaceutical�die composition may be in the form of a spray water-based (Hydrosol), in the form of an ointment or a gel based on hydrophilic physiologically acceptable media, such as biocompatible hydrophilic polymer, preferably selected from the group consisting of: starch, gelatin, collagen, cellulose ethers, carbopols, polyvinylpyrrolidone, polyvinyl alcohol, polyethylene oxide. Applied ointment or gel compositions is preferred.
To create pharmaceutical compositions can be used in ointment and gel forms used, in particular, in laser medicine and cosmetology. The main requirement to the ointment base is the absence of any significant absorption and/or scattering of electromagnetic radiation in the wavelength of the generation of the laser used and, accordingly, the maximum LPR nanoparticles. In addition, pharmaceutical compositions can be created on the basis of existing local drug action in ointment or gel form that meets a specified requirement.
For use in laser thermotherapy of the skin and its appendages, with the defeat of fungal, viral or bacterial origin, the pharmaceutical composition according to the invention may further comprise a means (substance, a drug) having, respectively, antifungal, antiviral and antibacterial action. In this CL�tea provides therapeutic effect of the composition by thermoinsulating and toxic effects of nanoparticles, and also due to the biocidal effect of the active ingredients of these drugs.
For example, for use in laser thermotherapy of the skin and its appendages, with the defeat of a fungal nature, the composition may also contain a means of antifungal activity, for example, selected from the group of antifungal drugs local action, consisting of clotrimazole, acteria, lamizila, loteria and other drugs of similar effect, and further contain a compound having a keratolytic effect, such as urea or salicylic acid.
For use in laser thermotherapy of the skin and its appendages, with the defeat of viral nature, the composition may also contain a means of antiviral action, for example, selected from the group of antiviral drugs, consisting of imidazole derivatives, triazole and allilamina and other drugs of similar effect.
For use in laser thermotherapy of the skin and its appendages, with the defeat of bacterial origin, the composition may also contain a means of antibacterial action, for example, selected from the group of antibacterial drugs operation, consisting of imidazole derivatives, triazole and allilamina and other drugs of similar effect.
Thus, according to the invention, �draw ELF, made of a dielectric or semiconductor mesoporous material such as mesoporous silica, can be a container to accommodate the above additional funds or their mixtures. The release of funds from the nucleus will occur as a result of partial or complete destruction of the metallic shell ELF under the action of laser radiation.
The above additional funds or mixtures thereof can be placed in used to create a composition of a hydrophilic physiologically acceptable medium.
Method laser thermotherapy of the skin and its appendages, with the defeat of infectious nature, is as follows in two stages.
At the 1st step of the way laser thermotherapy according to the invention is carried out, the choice of the pharmaceutical composition and its application to the subsequent irradiation region, on the 2nd stage is carried out laser irradiation region on which the pharmaceutical composition.
The choice of pharmaceutical compositions according to the invention is carried out from among the pharmaceutical compositions in embodiments described above and containing nanoparticles of a desired type, shape and size, made of solid or hollow metal selected from the group comprising gold, silver, copper and alloys of these metals, or in videocomposite nanoparticles with a given ratio of the sizes of the nucleus and the outer shell of these metals or their alloys, and, accordingly, characterized by a well-known position LPR in the wavelength range from 400 to 1100 nm, preferably in the wavelength range from 600 to 1100 nm, and dispersed in a physiologically acceptable carrier, characterized by the absence of absorption or poor absorption and/or weak scattering of light radiation in a specified wavelength range.
In the case of the proposed treatment of nails affected by onychomycosis, it is advisable to use a pharmaceutical composition, further comprising a means keratolytic action, such as urea, which will ensure the penetration of the nanoparticles into the nail plate to the main localization of the fungus and to avoid the complete or partial removal prior to processing by laser radiation.
The use in the pharmaceutical compositions according to the invention, the nanoparticles having a maximum LPR in the preferred wavelength range from 600 to 1100 nm, due to the fact that the specified range corresponds to the minimum absorption of electromagnetic radiation with biological tissues.
As a result, laser radiation with wavelengths in this range are able to penetrate the tissue to a greater depth, up to several centimeters. This poses�enables you to, in particular, treatment of onychomycosis without preliminary grinding or removal of the nail plate.
As nanoparticles having a maximum LPR in the preferred wavelength range from 600 to 1100 nm, using nanoparticles, representing the nanorods, hollow nanoparticles, composite nanoparticles with the structure "dielectric core-metallic shell.
Preferred is the use of composite nanoparticles with the structure of core-shell, because in their manufacture using known techniques of colloidal chemistry can be obtained by a set of particles having absorption in a wide spectral range due to the use of nanoparticles in the nuclei of the same size and varying only the thickness of the shell.
Fig.1 presents the dependence of the position of the localized surface plasmon resonance (wavelength λ) of the spherical composite nanoparticles having a core of silicon dioxide (SiO2) and a gold shell of different thickness, the ratio D/H of the core diameter D to the thickness H of the shell (curve 1), from which it follows that the increase of the ratio D/H from 2 to 50 leads to a shift position LPPR with a wavelength of 500 nm at a wavelength of 2000 nm (S. J. Oldenburg, R. D. Averitt, S. L. Westcott, N. J. Halas "Nanoengeneering of optical resonances". Chem. Phys. Lett., 1998, V. 288. P. 243). The use of this dependence allows for the creation of �farmacevticheskoi composition to produce a spherical composite nanoparticles having the geometrical parameters necessary to ensure compliance with wavelength LPR nanoparticles wavelength of the used laser radiation. Using a similar dependency situation LPR nanoparticle sizes and parameters of the structure and shape may be provided by the establishment of appropriate pharmaceutical compositions containing other nanoparticles with preset position LPR.
Selected pharmaceutical composition according to the invention, for example, in the form of a gel, ointment, spray applied to the area of the skin or its appendages, with the defeat of infectious nature. It does not require penetration of the nanoparticles into the cells of a pathogenic organism.
At the 2nd step of the way laser thermotherapy according to the invention the area of the skin or its appendages containing the specified pharmaceutical composition over a period of time after application of the composition, sufficient for penetration of the pharmaceutical compositions according to the invention in a biological tissue to the desired depth, is exposed to laser radiation at least at one wavelength, similar to that of the given wavelength LPR nanoparticles or equal to it, for a time at least sufficient to achieve the desired temperature.
According to the invention, when carrying out laser t�motherpie mode local hyperthermia carry the specified irradiation of the affected area, contains pre-printed specified pharmaceutical composition of laser radiation at the wavelength corresponding to the maximum of the localized surface plasmon resonance of the nanoparticles for a time sufficient to achieve a predetermined temperature exceeding the temperature is physiologically acceptable to the pathogenic cells.
At the same time as the laser source using a continuous or pulsed laser, the wavelength of the generation which is in the range of wavelengths from 400 to 1100 nm, preferably, in the wavelength range from 600 to 1100 nm.
When conducting laser therapy using the pharmaceutical composition according to the invention containing nanoparticles consisting of gold, silver, copper or their alloys, or composite nanoparticles with shells of these metals, therapeutic effect will be achieved through the combination thermoinsulating and toxic effects of nanoparticles. Preferred is the use of silver, as this metal is characterized by the highest biocidal activity.
The parameters and duration of laser irradiation are selected so that, firstly, to provide heating of the affected area to a temperature sufficient to kill pathogenic cells of the body,and secondly, to minimize the risk of injury to healthy tissue of the patient.
In the case of using the method of laser thermotherapy pharmaceutical compositions containing composite nanoparticles with a core of mesoporous material used as a container for additional funds for specific activities, such as these funds (medicines) fungicidal, antiviral, or other action, the release of funds from the nucleus will occur as a result of partial or complete destruction of the metallic shell ELF under the action of laser radiation. In this case, therapeutic effect of the composition is provided by thermoinsulating and toxic effects of metal nanoparticles, as well as due to the biocidal effect of the drug contained in the core composite nanoparticles or in the media.
The duration and number of sessions of laser thermotherapy and time intervals between them are determined according to the type of disease and stage of its development. In connection with that absorbing light radiation nanoparticles penetrated into the tissue to a predetermined depth, are immobilized in the tissue can be implemented and fractional radiation treatment of the affected area containing nanoparticles, with repeated temperature, previews� physiologically acceptable to the pathogenic cells, and subsequent cooling of the affected area, which will lead to improved efficiency of the method. The following are examples of preparation of different variants of the pharmaceutical compositions according to the invention, the implementation of laser thermotherapy according to the invention and of the method of treatment according to the invention.
Colloid-chemical method (Yong, K. - T., Y. Sahoo, M. T. Swihart, P. N. Prasad "Synthesis and plasmonic properties of silver and gold nanoshells on polystyrene cores of different size and of gold-silver core-shell nanostructures". Colloids Surf., A, 2006, V. 290, p. 89) was synthesized colloidal solution (Hydrosol) containing spherical ELF with a core diameter of 120 nm from a solid silicon dioxide and a shell thickness of 10 nm of silver. We measured the spectrum of colloidal solution (Hydrosol), shown in Fig.2 in the form of the dependence of optical density of the composition from the wavelength of the incident radiation (λ) (curve 2), thus the maximum LPPR of such particles was located at a wavelength of 800 nm and a molar extinction coefficient at this wavelength was ~7.5×1010M-1cm-1.
Based on the obtained Hydrosol and hydrophilic physiologically acceptable carrier gel of HPMC (Medigel, Helitec, Russia) were prepared pharmaceutical compositions in the form of ointments, ACC�SSS to the invention, comprising said nanoparticles having a maximum LPR at a wavelength of 800 nm at different concentrations from 1×109up to 2×1010nanoparticles in 1 ml of a composition that matched the silver content in the composition is from 0.001 to 0.01 wt.%, respectively. It was established that the absorption spectra of these pharmaceutical compositions, representing the dependence of optical density of the compositions of the wavelength of incident radiation X, which is quite different from the absorption spectrum of the above initial colloid solution (Hydrosol) ELF shown in Fig.2 in the form of the dependence of optical density of the composition from the wavelength of the incident radiation (λ) (curve 2), indicating that the HPMC gel is optically transparent in the wavelength range from 400 nm to 1100 nm and has no effect on the absorption of radiation by the nanoparticles.
In created and described above in example 1 pharmaceutical composition additionally added the keratolytic agent is urea at a concentration of from 10 to 30 wt.%.
It was established that the absorption spectra of these pharmaceutical compositions, representing the dependence of optical density of the compositions of the wavelength of incident light λ, which is quite different from the absorption spectrum of the above original colloidal solution (Hydrosol) ELF, performance�tion in Fig.2 in the form of the dependence of optical density of the composition from the wavelength of the incident radiation (λ) (curve 2), and did not differ in shape from the absorption spectra obtained, as indicated above, pharmaceutical compositions in the form of ointments, which suggests that the presence in the pharmaceutical composition of urea has no effect on the absorption of radiation of composite nanoparticles.
Colloid-chemical method (Kartseva M. E., O. V. Dement'eva, M. A. Filippenko, V. M. Rudoy "Anisotropic particles with different morphology of silver membranes: synthesis and optical properties". The colloid. Phys., 2011, vol. 73, p. 334) synthesized colloidal solution (Hydrosol) containing anisotropic composite nanoparticles with a core length of 200 nm and a diameter of 50 nm from the (HYDR)oxide iron (FeOOH) and a shell thickness of 5 nm of silver. We measured absorption spectrum of colloidal solution (Hydrosol), shown in Fig.3 in the form of the dependence of optical density of the composition of the wavelength of incident radiation X (curve 3), thus the maximum LPPR such nanoparticles was located at a wavelength of approximately 1050 nm and the molar extinction coefficient at this wavelength was ~4.5×1010M-1cm-1.
Based on the obtained Hydrosol and hydrophilic physiologically acceptable carrier gel of HPMC (Medigel, GE�tech, Russia) were prepared pharmaceutical compositions in the form of ointments according to the invention comprising these anisotropic nanoparticles having a maximum LPR at the wavelength of 1050 nm at various concentrations from 1×109up to 2×1010nanoparticles in 1 ml of a composition that matched the silver content in the composition is from 0.0007 to 0.007 wt.%, respectively.
It was established that the absorption spectra of these pharmaceutical compositions, representing the dependence of optical density of the compositions of the wavelength of incident radiation X, which is quite different from the absorption spectrum of the above original colloidal solution (Hydrosol) of anisotropic nanoparticles is shown in Fig.3 in the form of the dependence of optical density of the composition of the wavelength of incident radiation X (curve 3), indicating that the HPMC gel is optically transparent in the wavelength range from 400 nm to 1100 nm and has no effect on the absorption of radiation by the nanoparticles.
To investigate the efficacy of using the pharmaceutical compositions according to the invention in the method of laser thermotherapy were prepared pharmaceutical compositions according to the invention, as described�th in Example 1 contains: gel HPMC as hydrophilic physiologically acceptable carrier ointment bases, 15 wt.% urea and ELF spherical, having a core diameter of 120 nm from a solid silicon dioxide and a shell thickness of 10 nm made of silver and is characterized LPPR with the maximum at a wavelength of 800 nm at concentrations ELF in 1 ml of the composition is from 1×109up to 2×1010that matched the silver content in the composition is from 0.001 to 0.01 wt.%, respectively.
The obtained pharmaceutical compositions with a volume of 1 ml were placed in a quartz cuvette and exposed to laser radiation with a wavelength of 808 nm, which is close to the wavelength of maximum LPPR these nanoparticles. At the same time as the radiation source used laser power of 0.5 W, operating in the continuous mode. For comparison, laser radiation at a specified wavelength in the above conditions was subjected to and the HPMC gel volume of 1 ml, used as a hydrophilic physiologically acceptable ointment base specified pharmaceutical compositions. The maximum irradiation time of HPMC gel and the indicated pharmaceutical compositions was 20 min. temperatures of HPMC gel and the indicated pharmaceutical compositions reached at the end of their laser treatment, are shown in the table. Heating of the gel carbap�La and pharmaceutical compositions to a specified final temperature was 5-7 min.
The table shows that the exposure time (20 minutes) the temperature rise of the HPMC gel was low (4°C) compared with the increase of temperature Pharma�quarter of the compositions according to the invention (10-19°C depending on the concentration of spherical nanoparticles in the composition), moreover, with increasing concentration of these nanoparticles was increased and the final temperature of the pharmaceutical composition. This indicates that heating of the pharmaceutical compositions according to the invention has occurred is due to the absorption of nanoparticles laser radiation and its transformation into heat energy. Moreover, as follows from the table that has been heating the pharmaceutical composition according to the invention to temperatures (43-45°C), physiologically unacceptable to pathogenic cells, the application of the above compositions in laser thermotherapy will lead to the destruction of pathogenic cells. The data in the table indicate the dependence of the magnitude of attainable temperature from the content of the ELF in the composition, allowing for the laser thermotherapy to choose a pharmaceutical composition of a particular composition in accordance with the desired maximum temperature in the irradiated region, for example, depending on the condition of the affected area.
A method for the treatment of skin and its appendages with infectious lesions, was performed on the example of the treatment of nails affected by fungal disease, with research EF�aktivnosti use of the technique of laser thermotherapy in conditions of hyperthermia and the use of pharmaceutical compositions according to the invention.
The nail plate is affected, presumably, onychomycosis, was cut and divided into two parts. For diagnosis one part of the plates processed according to the instructions of the company to diagnostic Remel set BactiDrop Calcofluor white: a specified surface of the nail were consistently applied drops of 10% KOH solution and BactiDrop Calcofluor white, then the preparation was covered with a cover glass and examined in the fluorescence microscope. Discovered the fungus. Additional planting has allowed to establish that this is Trichophyton rubrum, which indicates the defeat of the nail onychomycosis.
On the second part of the nail plate was applied 200 μl of the pharmaceutical composition according to the invention containing HPMC gel, 15 wt.% urea and ELF spherical, having a core diameter of D=120 nm from a solid silicon dioxide and a shell of thickness H=10 nm of silver, in numerical concentration of 2×1010ml-1and characterized by the position of the maximum LPR near the wavelength of 800 nm. After 30 min said second portion of the nail plate was subjected to laser radiation with a wavelength of 808 nm. We used a laser power of 0.5 W, operating in the continuous mode. The temperature control of the surface of the nail is coated with the specified pharmaceutical composition was performed using a thermal imager testo 875-1. Time region�tion was 1 min, thus for the specified time, the temperature of the surface of the nail has reached 47°C. To establish the viability of the cells of the fungus after this treatment used method of staining with neutral red.
Microscopic analysis of the stained sample did not reveal living cells Trichophyton rubrum (painted with vacuoles), indicating that the session of laser therapy in the mode of local hyperthermia in these conditions led to the complete destruction of the fungus.
- the presence in the compositions of metal nanoparticles with biocidal properties, provides additional antibacterial treatment the affected area in the process of laser thermotherapy, and after it.
Application of the method of laser thermotherapy according from�bretania with the use of pharmaceutical compositions according to the invention enables selection of a composition in accordance with the selected modes of exposure while in the area of infectious lesions of the guarantee to achieve the selected temperature mode during the selected time leading to a given therapeutic effect when used to secure the body to the mode of laser radiation.
Application of the method of treatment of the skin and its appendages, with the defeat of fungal, viral or bacterial origin, using the laser thermotherapy according to the invention provides high efficiency laser radiation exposure and a given outcome.
Specialists in the field of medicine, it must be clear that the pharmaceutical composition according to the invention, in a method of laser thermotherapy according to the invention and in the method of treatment of the skin and its appendages, with the defeat of fungal, viral or bacterial origin, may be made enhancements and modifications not beyond the scope of the claims.
As described above, obtaining pharmaceutical compositions according to the invention and implementation of the method of laser thermotherapy according to the invention and of the method of treatment of the skin and its appendages, with the defeat of fungal, viral or bacterial origin, may be implemented using known technologies and known equipment that provides the opportunity and� wide application in medicine.
1. Pharmaceutical composition for external use laser thermotherapy of the skin and its appendages with infectious lesions containing nanoparticles, characterized by light irradiation, at least one of the localized surface plasmon resonance in the wavelength range from 400 to 1100 nm, dispersed in a physiologically acceptable carrier, characterized by the absence of absorption or poor absorption and/or weak scattering of light radiation in a specified wavelength range, and with biocidal properties.
2. A composition according to claim 1, characterized in that the nanoparticles are spherical nanoparticles consisting of metals selected from the group comprising gold, silver, copper and alloys of these metals.
3. A composition according to claim 1, characterized in that said nanoparticles are anisotropic nanoparticles consisting of metals selected from the group comprising gold, silver, copper and alloys of these metals.
4. A composition according to claim 1, characterized in that said nanoparticles are hollow nanoparticles composed of metals selected from the group comprising gold, silver, copper and alloys of these metals.
5. A composition according to claim 1, characterized in that the nanoparticles are composite nanoparticles with structure�Oh core-shell, in which the core is made of a dielectric or semiconductor material and surrounded by a shell of metal selected from the group including gold, silver, copper and their alloys.
6. A composition according to claim 5, characterized in that the composite nanoparticles have a spherical shape.
7. A composition according to claim 5, characterized in that the core of these composite nanoparticles are made of solid silicon dioxide.
8. A composition according to claim 5, characterized in that the core of these composite nanoparticles made of a material with a porous structure.
9. A composition according to claim 8, characterized in that as a material with a porous structure using mesoporous silica.
10. A composition according to claim 5, characterized in that the composite nanoparticles are anisotropic in shape.
11. A composition according to claim 5, characterized in that the core of these composite nanoparticles made of oxide or hydroxide of iron.
12. A composition according to claim 1, characterized in that contains the nanoparticles in a concentration of from 0.0001 to 5.0 wt.% based on the content of the metal or alloy of metals.
13. A composition according to claim 12, characterized in that includes the nanoparticles, preferably in a concentration of from 0.005 to 0.10 wt.% based on the content of the metal or alloy of metals.
14. A composition according to claim 1, characterized in that � spray water-based.
15. A composition according to claim 1, characterized in that is made in the form of an ointment or a gel based on hydrophilic physiologically acceptable carrier.
16. A composition according to claim 15, characterized in that the hydrophilic physiologically acceptable carrier contains a hydrophilic biocompatible polymer.
17. A composition according to claim 16, characterized in that the biocompatible hydrophilic polymer, preferably selected from the group consisting of: starch, gelatin, collagen, cellulose ethers, carbopols, polyvinylpyrrolidone, polyvinyl alcohol, polyethylene oxide.
18. A composition according to claim 1, characterized in that the nanoparticles entered in the specified pharmaceutical composition in the form of colloidal solution.
19. A composition according to claim 1, characterized in that the nanoparticles entered in the specified pharmaceutical composition in powder form.
20. A composition according to claim 19, characterized in that the powder obtained by freeze drying of colloidal solution containing the nanoparticles.
21. A composition according to claim 1, characterized in that is adapted for use in laser thermotherapy of the skin and its appendages, with the defeat of fungal, viral or bacterial origin, and further comprises a means of having, respectively, antifungal, antiviral and antibacterial action.
22. The compositing�tion according to claim 21, characterized in that is adapted for use in laser thermotherapy of the skin and its appendages, with the defeat of a fungal nature, and thus contains the specified remedy antifungal activity selected from the group of antifungal drugs local action, consisting of clotrimazole, acteria, lamizila, loteria and other drugs of similar effect.
23. A composition according to claim 21, characterized in that it further comprises a means of having a keratolytic effect.
24. A composition according to claim 23, characterized in that the means keratolytic action selected from the group consisting of urea and salicylic acid.
25. A composition according to claim 21, characterized in that is adapted for use in laser thermotherapy of the skin and its appendages, with the defeat of viral nature, and it contains the antiviral agent of the action selected from the group of antiviral drugs, consisting of imidazole derivatives, triazole and allilamina and other drugs of similar effect.
26. A composition according to claim 21, characterized in that is adapted for use in laser thermotherapy of the skin and its appendages, with the defeat of bacterial origin, and thus provides a means of antibacterial action selected from the group of antibacterial drugs operation, comprising�her from imidazole derivatives, triazole and allilamina and other drugs of similar effect.
27. A composition according to claim 21, characterized in that said means or mixtures thereof are placed in the core of composite nanoparticles having a structure of core - shell, and wherein the core is made of a dielectric or semiconductor mesoporous material and surrounded by a shell of metal selected from the group including gold, silver, copper and their alloys.
28. A composition according to claim 21, characterized in that the funds or their mixture is placed in a hydrophilic physiologically acceptable medium.
29. A composition according to claim 1, characterized in that preferably comprises nanoparticles, characterized by at least one of the localized surface plasmon resonance in the wavelength range from 600 to 1100 nm.
30. Method laser thermotherapy of the skin and its appendages, with the defeat of infectious nature, in which an area having a specified lesion, causing a pharmaceutical composition containing the nanoparticles, characterized by at least one of the localized surface plasmon resonance in the wavelength range from 400 to 1100 nm, dispersed in a physiologically acceptable carrier, characterized by the absence of absorption or poor absorption and/or weak scattering of light radiation in the specified range length� waves and thus having biocidal properties; then the region containing the specified pharmaceutical composition is subjected to laser irradiation, at least one wavelength from the range of wavelengths close to the wavelength of the localized surface plasmon resonance of the nanoparticles contained in the composition, or equal, to achieve the desired temperature of heating of the region specified.
31. A method according to claim 30, in which the use of a pharmaceutical composition containing spherical nanoparticles consisting of metals selected from the group comprising gold, silver, copper and alloys of these metals.
32. A method according to claim 30, in which the use of a pharmaceutical composition containing anisotropic nanoparticles consisting of metals selected from the group comprising gold, silver, copper and alloys of these metals.
33. A method according to claim 30, in which the use of a pharmaceutical composition containing a hollow nanoparticles composed of metals selected from the group comprising gold, silver, copper and alloys of these metals.
34. A method according to claim 30, in which the use of a pharmaceutical composition containing composite nanoparticles with the structure of the core-shell in which the core is made of a dielectric or semiconductor material and surrounded by a shell of metal selected from the group, including�ment gold, silver, copper and their alloys.
35. A method according to claim 34, in which the use of a pharmaceutical composition containing composite nanoparticles having a spherical shape.
36. A method according to claim 34, in which the use of a pharmaceutical composition containing composite nanoparticles having a spherical shape with the nucleus from a solid silicon dioxide.
37. A method according to claim 34, in which the use of a pharmaceutical composition containing composite nanoparticles having a spherical shape with a core of a material with a porous structure.
38. A method according to claim 37, in which the use of a pharmaceutical composition containing composite nanoparticles having a spherical shape with the nucleus of mesoporous silica.
39. A method according to claim 34, in which the use of a pharmaceutical composition containing composite nanoparticles with anisotropic shape.
40. A method according to claim 39, in which the use of a pharmaceutical composition containing composite nanoparticles with a core of an oxide or (HYDR)oxide of iron.
41. A method according to claim 30, in which the use of a pharmaceutical composition comprising said nanoparticles in a concentration of from 0.0001 to 5.0 wt.% based on the content of the metal or alloy of metals.
42. A method according to claim 41, in which the use of a pharmaceutical composition containing nanoparticles, preferably in a concentration of from 0.005 to 0.10 wt.% based on the content of the metal or alloy of metals.
43. A method according to claim 30, in which the use of the pharmaceutical composition is in the form of spray is water-based.
44. A method according to claim 30, in which the use of the pharmaceutical composition, in the form of ointment or gel based on hydrophilic physiologically acceptable carrier.
45. A method according to claim 44, in which the use of a pharmaceutical composition containing as the hydrophilic physiologically acceptable carrier is a hydrophilic biocompatible polymer.
46. A method according to claim 45, in which the biocompatible hydrophilic polymer is preferably selected from the group consisting of: starch, gelatin, collagen, cellulose ethers, carbopols, polyvinylpyrrolidone, polyvinyl alcohol, polyethylene oxide and mixtures thereof.
47. A method according to claim 30, in which the use of a pharmaceutical composition containing the nanoparticles entered in the specified pharmaceutical composition in the form of colloidal solution.
48. A method according to claim 30, in which the use of a pharmaceutical composition containing the nanoparticles entered in the specified pharmaceutical composition in powder form.
49. A method according to claim 48, in which the use of a pharmaceutical composition containing the nanoparticles entered in the specified pharmaceutical composition in the form of a powder obtained by freeze drying of colloidal solution containing the nanoparticles.
50 a Method according to claim 30, in which the pharmaceutical composition further comprises a means of having, respectively, antifungal, antiviral and antibacterial action.
51. A method according to claim 50, in which the means of having antifungal activity selected from the group of antifungal drugs local action, consisting of clotrimazole, acteria, lamizila, loteria and other drugs of similar effect.
52. A method according to claim 50, in which the pharmaceutical composition further comprises a means of having a keratolytic effect.
53. A method according to claim 52, in which the means of having a keratolytic effect selected from the group consisting of urea and salicylic acid.
54. A method according to claim 50, which means the antiviral action selected from the group of antiviral drugs, consisting of imidazole derivatives, triazole and allilamina and other drugs of similar effect.
55. A method according to claim 50, in which the means of antibacterial action selected from the group of antibacterial drugs operation, consisting of imidazole derivatives, triazole and allilamina and other drugs of similar effect.
56. A method according to claim 50, in which the use of a pharmaceutical composition containing the funds or their mixture disposed in the composite core of nanoca�TCI having the structure of core-shell, and wherein the core is made of a dielectric or semiconductor mesoporous material and surrounded by a shell of metal selected from the group including gold, silver, copper and their alloys.
57. A method according to claim 50, in which the use of a pharmaceutical composition containing the funds or their mixture, placed in a hydrophilic physiologically acceptable medium.
58. A method according to claim 30, wherein the source of the specified light radiation using a laser, the wavelength of the generation which is in the range of wavelengths from 400 to 1100 nm.
59. A method according to claim 30, wherein, preferably, use of the pharmaceutical composition containing the nanoparticles, characterized by at least one of the localized surface plasmon resonance in the wavelength range from 600 to 1100 nm, and as the source of the specified light radiation using a laser, the wavelength of the generation which is, preferably, in the wavelength range from 600 to 1100 nm.
60. A method according to claim 30, in which the specified source of light radiation using a laser having a continuous or pulsed mode of generation of radiation.
61. A method according to claim 30 in which the laser thermotherapy in local mode hyperthermia carry the specified irradiation affected �area, containing specified previously applied pharmaceutical composition, light radiation at the wavelength corresponding to the maximum of the localized surface plasmon resonance of these nanoparticles for a time sufficient to achieve a predetermined temperature exceeding the temperature is physiologically acceptable to the pathogenic cells.
62. A method for the treatment of skin and its appendages with the infectious nature lesions using laser thermotherapy, which use the method of laser thermotherapy according to PP.30-61, using the pharmaceutical composition according PP.1-29.
63. A method according to claim 62, in which for the treatment of skin and its appendages, with the defeat of fungal, viral or bacterial nature, using laser thermotherapy in local hyperthermia using the method of laser therapy with the use of a pharmaceutical composition, characterized by the maximum temperature of its heat up under the action of irradiation, the above physiological temperature of the cells of the pathogen.
SUBSTANCE: at a core (1) made of a steel wire layers of current-conducting wires of two types are wound - aluminium wire (2) and nanocomposite wire (3). The layers of wire (3) are alternated with the layers of wire (2). The layer of wire (3) is wound to the core (1). The wire (3) is formed of a wire stock (wire rod) produced of a nanocomposite material based on aluminium with a nanoparticle filler made as multilayer carbon nanotubes and reinforced in the process of multiple cold drawing of the wire stock up to the preset diameter.
EFFECT: increased capacity, mechanical strength and resistivity to sagging without an increase in its weight.
SUBSTANCE: invention relates to a microbubble generator and to a device for microbubble generation. One of the aspects of the claimed invention is represented by the microbubble generator, containing a vortex chamber, an opening for the supply of a fluid medium, connected to the vortex chamber, with the opening for the fluid medium supply being intended for the supply of the fluid medium along the line, which is tangent to the internal surface of the vortex chamber, and an output pipe, intended for directing the fluid medium in the direction, in fact, perpendicular to the direction of the fluid medium introduction. The output pipe passes through the surface of the vortex chamber wall and projects into the internal space of the vortex chamber. In accordance with the said configuration, it is possible to reduce the loss of kinetic energy of the vortex flow of the fluid medium by the isolation of the introduced fluid medium trajectory.
EFFECT: invention provides obtaining the microbubble generator, in which the size of the formed microbubbles can be reduced, that provides effective formation of the bubbles with a nanometric range size.
SUBSTANCE: light-emitting diode (LED) comprises a base, a light-emitting structure, a first electrode and a second electrode. An U-shaped electroconductive suspension for the light-emitting structure, which is transparent for the emitted light, is made on the base. The suspension lies on the base with one arm and is rigidly connected to the base. There is a series of elements rigidly connected to the arms between the arms in the direction from the base. The elements comprise an insulating layer, a first electrode, a layer which acts a mirror and a heatsink and a light-emitting structure. The LED is made as follows. A multilayer film element is formed on the base. The materials used are such that the layer geometry and intrinsic mechanical stress thereof enable to obtain a light-emitting structure and U-shaped suspension which is electroconductive and transparent for the emitted light. The step of forming the film element includes successively making a set of layers with intrinsic mechanical stress and a set of layers of the light-emitting structure. For the latter, two areas are formed, which are arranged with a gap with a depth to the last set of layers with intrinsic mechanical stress. Areas of the film element are obtained - an area which corresponds to the arm lying on the base, an area which corresponds to the arm connected to the light-emitting structure and an area corresponding to a loop. An insulating layer, on which the first electrode is made, is formed on the area of the film element which corresponds to the arm lying on the base. A layer which acts the mirror and heatsink is formed on the area of the film element which corresponds to the arm connected to the light-emitting structure. The film element is then partially separated from the base, leaving it connected on the area which corresponds to the arm lying on the base. The set of layers with intrinsic mechanical stress is transformed under the action of the intrinsic mechanical stress into U-shaped suspension with a loop and the obtained light-emitting structure between the arms. During separation, the set of layers of the light-emitting structure with the layer which acts as a mirror and a heatsink is turned over and the latter is brought into contact with the first electrode to form a rigid connection.
EFFECT: high efficiency of converting electrical energy into light energy and heat removal, reducing the dimensions of LEDs and integration with other optoelectronic devices on a single base.
SUBSTANCE: invention relates to powder metallurgy, in particular to powder production for application of wear- and corrosion-resistant coatings with high adhesive and cohesive strength by method of cold gas-dynamic spattering. The composite nanostructured powder for coatings application by the method of cold gas-dynamic spattering comprises particles containing metal core out of Hadfield steel, clad layer with thickness 4-8 mcm out of aluminium powder, diffusion layer out of intermetallic compounds with thickness 0.6-1.2 mcm created at border of the core and clad layer during annealing, and reinforced surface layer created during interaction of the clad layer and oxide reinforcing agent comprising nanoparticles 10-100 nm, at that the volume share of the oxide reinforcing agent in the clad layer is 30-40%.
EFFECT: coatings made from the suggested composite nanostructured powder have high adhesive and cohesive strength, uniform hardness distribution through the coating cross-section.
SUBSTANCE: invention relates to the field of selective catalytic reduction of nitrogen oxides, namely to a material of a carrier for the catalyst, used in the said process. The claimed carrier material represents particles of anatase titanium dioxide, including ≥85% by dry weight of TiO2 and ≤10% by dry weight of SiO2, with (i) SiO2 being mainly in the form, selected from the group, consisting of forms with the low molecular weight, nanoparticles and their combinations; and (ii) at least 50% of silicon atoms being in states Q3, Q2, Q1 and Q0 of the coordination environment. The invention also relates to a catalytic device for the neutralisation of Diesel exhaust, including such particles, a system for Diesel exhaust regulation, including the said catalytic device, a method in which the conversion of nitrogen oxides is catalysed in the presence of the claimed particles of anatase titanium dioxide, as well as to methods of obtaining the said particles.
EFFECT: claimed particles make it possible to increase the thermal stability of the final catalyst with the preservation or increase of the catalytic activity for the selective catalytic reduction of nitrogen oxides from mobile devices, operating on lean mixtures.
SUBSTANCE: electrode coating contains the following components, wt %: ferrochrome - 58.0-60.0, ferroboron - 14.0-16.0, marble - 5.0-7.0, ferrosilicon - 3.5-4.5, fluorspar - 3.5-4.5, ferromanganese - 1.5-3.5, graphite - 5.5-6.5, potash - 0.5-1.5 and nanopowder of titanium carbonitride - 1.5-3.0. The electrode coating can be applied to metal rods from steel grade Sv-08A.
EFFECT: composition of the coating allows obtaining electrode paste with high plasticity, and electrodes with such coating provide for obtainment of deposited metal with hardness of up to 66 HRC, increased wear resistance and continued operating stability of reworked parts.
SUBSTANCE: invention relates to military robotics and can be used for proportional increase in force of combatant and at cargo handling. This exoskeleton comprises carcass system, drives, electronic control system and power supply battery. Said carcass system consists of black-reinforced plastic panel following the trunk rear shape and articulated leverage of reinforced-black tubes. Note here that carcass leverage drives are made of solid aerogel composed of carbon nanotubes with admixture of rubber shaped to 40-120 mm diameter cylinders with conical sharpening on ends. Said drives are attached to the levers by clamping of conical ends with the help of synthetic fabric bands impregnated with epoxy resin and tied by steel rivets.
EFFECT: electric power saving, increase in force and self-contained operation time, maximised combat efficiency.
SUBSTANCE: uniform, continuous and dense layer of pyrolytic carbon has width of carbon coating, close to monolayer coating, equal 0.4-0.5 nm, density of precipitated carbon coating, equal ρC = 2.0-2.1 g/cm3, specific surface SBET = 90-200 m2/g, cumulative volume of pores ΣVpore≤0.4 cm3/g, average size of pores DBET≤10 nm, most probable size of pores DBJH = 5-7 nm with absence of micro pores. Invention also relates to method of production of such mesoporous composite material.
EFFECT: claimed mesoporous composite material has high-quality thin carbon coating, which totally and uniformly covers external surface and walls of pores of said material.
SUBSTANCE: solar element includes cathode and anode, each having external and internal flexible layers, at that these cathode and anode are located such that their internal layers are opposite each other with clearance filled by the electrolyte, at that the external layer of the cathode is made out of transparent polymer material, and its internal layer is made out of carbon nanotubes, the external layer of the anode is made out of conducting material, and its internal layer is made out of nanoparticles of solid state material, dye-sensitised.
EFFECT: simplified process of solar elements manufacturing, reduced price, and increased flexibility.
SUBSTANCE: object is positioned on porous substrate, fixed to the substrate surface and scanned by probe microscopy method. Substrate with through pores of smaller size than the diameter of a study object is used, and an object is fixated by laminar flow of liquid or gas supplied to the substrate from the side of scanning, with clamping force exerted by the flow on an object within 10-12-10-3 N range.
EFFECT: possible study of structures and mechanical properties of organic and inorganic objects, enhanced information content of nano and micro object studies by probe microscopy.
SUBSTANCE: invention relates to the pharmaceutical industry and represents a pharmaceutical composition for the external application for the treatment of skin diseases in the form of a cream, which includes as an active substance methylprednisolone aceponate in a therapeutically effective amount and a lipophilic base, characterised by the fact that as the lipophilic base it contains petrolatum, liquid paraffin and oil of castor oil plant seeds and additionally white bee wax, with the components of the composition being in a specified ratio in g/100 g of the composition.
EFFECT: invention provides the creation of the stable composition, improved pharmacological properties and absence of an irritating effect.
SUBSTANCE: invention refers to pharmaceutical industry and represents an anti-allergic agent containing polysaccharide containing galactose, glucose and rhamnose as ingredients, wherein polysaccharide contains galactose, glucose and rhamnose in molar ratio 3-5:1-3:1, and polysaccharide has certain structure.
EFFECT: invention provides extending the range of antiallergic agents.
SUBSTANCE: pharmaceutical composition in the form of a tablet with an erodible matrix, which contains one or more fumaric acid ethers, as well as a rate-controlling agent, representing hydroxypropylcellulose and a binding agent, representing lactose, with the decomposition of the said degradable matrix providing the controlled release of the said fumaric acid ether (ethers).
EFFECT: provision of the controlled release of fumaric acid ether (ethers).
SUBSTANCE: invention relates to the beauty industry, representing a gel-like composition for topical application, containing salicylic acid with the concentration of ca. 17 wt %, elastic collodion in the amount of 5 to 10 wt % and ethyl lactate in the amount of 20 to 25 wt %, where the elastic collodion contains 65.8 wt % diethyl ether, 24.3 wt % ethanol, 2 wt % camphor, 3 wt % castor oil and 4.9 wt % nitro-cellulose.
EFFECT: invention provides excellent stability, even drying and the formation of a uniform film.
SUBSTANCE: melanin having water-solubility of at least 80% and an paramagnetic centre concentration of at least 8·1017 spin/g is administered orally into the animals having been exposed to the radiation in a dose high enough to cause a spinal radiation injury; melanin is administered after dissolved in distilled water in the effective concentration. Melanin water is used as drinking water for the mice having been exposed to single and fractionated acute radiation, which is able to cause acute radiation disease. Melanin water is taken from the 1st to 30th day following the single radiation, or from the 1st day of the fractionated radiation to the 30th day on completion of the radiation.
EFFECT: higher survival rate, faster recovered haemopoiesis, body weight and orientation and motion activity.
SUBSTANCE: invention refers to medicine, more specifically to clinical dentistry. The invention represents a composition for treating erosive ulcerative and exudative hyperaemic forms of oral lichen planus.
EFFECT: implementing the invention provides high oral adhesion of the preparation, increases the therapeutic concentration of the preparation in the area of involvement (inflammation), accelerates the length of treatment (reduces the size of erosion, the length of epithelisation of erosions).
SUBSTANCE: pharmaceutical composition possessing a therapeutic action on various skin pathologies contains triptantrin, chitosan and distilled water, a lanoline and Vaseline mixture and protein-nucleic hydrolyzate of the salmonid fishes milt in a certain mixture ratio.
EFFECT: composition enables increasing the clinical effectiveness in the skin pathologies of various origins and extending the range of pharmaceutical compositions having the therapeutic effect on the various skin pathologies.
SUBSTANCE: invention refers to pharmaceutical and cosmetic industries, namely to an elastase inhibitor. The elastase inhibitor containing active ingredients presented by raspberry (Rubus idaeus L.) extract and hydroxyproline in the dry state in a certain amount, wherein the raspberry extract is prepared by using an extraction solvent specified in a group consisting as follows: water, methanol, ethanol, hydroethanol, 1,3-butylene glycol, acetone and/or ethyl acetate. The composition for external skin application containing the elastase inhibitor.
EFFECT: agent is the effective elastase inhibitor.
SUBSTANCE: invention relates to pharmaceutical industry, namely to production of medications for treating dermatosis. Medication according to invention, made in form of cream, contains mometasone furoate, preservative, hydrophilic no-aqueous solvent, emulsifying agent of 1st kind, emulsifying agent of 2nd kind, emollient, disodium edetate (trilon B), pH-regulating agent, and purified water in quantities, given in invention formula.
EFFECT: invention can be applied for treating inflammatory diseases and itching in case of dermatosis, yielding to glycocorticosteroid therapy.
SUBSTANCE: invention relates to the field of organic chemistry, namely to novel derivatives of pyrazole pyridine of formula , as well as to its tautomers, geometrical isomers, enantiomers, diastereomers, racemates and pharmaceutically acceptable salts, where G1 represents H; G2 represents -CHR1R2; R1 and R2 independently on each other are selected from H; C1C6-alkoxy-C1C6-alkyl; C1-C6-alkyl; optionally substituted phenyl; optionally substituted phenyl-C1-C6-alkyl; optionally substituted morpholine-C1-C6-alkyl; or -CHR1R2 together form a ring, selected from an optionally substituted C3-C8-cycloalkyl and substituted piperidine; G3 is selected from an optionally substituted C1C6-alkoxy -C1-C6-alkyl; C1-C6-alkyl; substituted phenyl; substituted phenyl-C1C6-alkyl; G4 is selected from a substituted acyl-C1C6-alkyl, where acyl represents a group -CO-R and R stands for H or morpholine; optionally substituted C1-C6-alkyl; optionally substituted phenyl or indene; substituted phenyl-C1-C6-alkyl; optionally substituted pyridine- or furanyl-C1C6-alkyl; morpholine- or piperidine-C1-C6-alkyl; G5 represents H; where the term "substituted" stands for the groups, substituted with 1 to 5 substituents, selected from the group, which includes a "C1-C6-alkyl," "morpholine", "C1-C6-alkylphenyl", "di-C1-C6-alkylamino", "acylamino", which stands for the group NRCOR", where R represents H and R" represents a C1-C6-alkyl, "phenyl", "fluorine-substituted phenyl", "C1-C6-alkoxy", "C1-C6-alkoxycarbonyl", "halogen". The invention also relates to a pharmaceutical composition based on the formula (I) compound and particular compounds.
EFFECT: obtained are the novel derivatives of pyrasole pyridine, useful for the treatment and/or prevention of disorders or states, associated with NADPH-oxidase.
SUBSTANCE: nucleus of lens is fragmented completely by femtosecond laser light at power 7,000-8,500 nJ; that is followed by making a corneal flap incision, dilating the pupil mechanically, and separating the synechias. A continuous circular capsulorhexis is performed, and the fragmented crystalline substance is emulsified. If observing degree II nuclear density, the nucleus is fragmented on 8 segments, while degrees III and IV requires fragmenting the nucleus on 8 segments in a combination with the circular incision in the centre 3 mm in diameter.
EFFECT: method provides creating the optimum conditions for phakoemulsification of the crystalline lens in the narrow rigid pupil and iris-lens synechias for enabling the adequate fixation of the IOL in the capsular sac with reducing intraoperative injuries and preventing the complications.

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