Method for local reinforcement of molecular oxygen in skin derma

FIELD: medicine.

SUBSTANCE: method refers to medicine, and may be used for treating pathologies of the near-surface skin, and particularly for low-intensity laser and photodynamic therapy. A depth of the pathological derma is determined. If the depth is less than 0.22 mm, the region is exposed to light beam at wave length 418±5 nm. At the depth within the range of 0.22 mm to 0.9 mm, the region is exposed at wave length 575±5 nm. The depth within the range of 0.9 mm to 2.5 mm enables the exposure at wave length 585±5 nm. The depth within the range of 0.9 mm to 2.5 mm requires the region to be exposed at wave length 600±5 nm.

EFFECT: method enables increasing a number of the formed oxygen molecules formed in the skin derma at the different depths in the derma due to blood oxyhaemoglobin dissociation under the influence of light of a certain spectral composition.

2 dwg

 

The invention relates to non-invasive local generation of oxygen at the specified depth in the dermis due to photodissociation of oxyhemoglobin in the blood under the action of light of a certain spectral composition. It can be used in the treatment of pathologies of the surface of the skin, in particular when low-intensity laser and photodynamic therapy.

It is known [1]that irradiation of skin tissue is illuminated with light of frequency ν (or wavelength λ=c/ν, where c is the speed of light in the medium) is photodissociate oxyhemoglobin HbO2that is degraded to deoxyhemoglobin Hb and molecular oxygen O2:

.

This mechanism is used to raise the level O2in skin tissues with the aim of eliminating hypoxia (lack of oxygen), stimulating aerobic (associated with the consumption of oxygen) metabolism in cells and achieve appropriate therapeutic effects. It is important to provide the ability to generate oxygen at the desired depth in the tissue, where, for example, is pathological or tumor site with a photosensitizer with light - or photo dynamic therapy [2].

A known method of generating oxygen (oxygenation) in the tissue, which consists in the fact that at the same time spend hyperbaric oxygenation (HBO) and discontinue the laser irradiation at a wavelength of from 600 to 1000 nm, and thus non-invasive influence through the skin on the entire thickness of the dermis, in which it is necessary to increase the concentration of oxygen [3].

The disadvantage of this method is the complexity due to the need to combine HBO and radiation, as well as the inability to locally increase the concentration of oxygen at the desired depth in the tissue, since the process includes HBO oxygenation of the whole organism. For implementing the method of HBOT requires bulky stationary equipment. In addition, it causes a high risk of oxygen toxemia (blood poisoning toxins bacteria) as a result of prolonged exposure to O2on the body at high pressure.

Closest to the proposed method is a method [4] increasing the concentration of molecular oxygen in the thickness of the skin tissue, which consists in irradiating the skin surface with light at a wavelength of λ=632.8 nm and a concomitant increase in local temperature exposure of tissue to about 42°C. the Disadvantage of this method is the small number of generated molecules O2due to the use of light with λ=632.8 nm. Furthermore, the method does not provide the ability to selectively increase the level of oxygenation of the tissue at the desired depth, where it can be subject to treatment of a pathological area.

The present invention is to increase the number formed by the oxygen molecules in the dermis of skin tissue, as well as providing the opportunity for the barb to selectively maximize the generation of O 2at different depths in the dermis.

The solution of this problem is achieved by the fact that the way local increase of the concentration of molecular oxygen in the dermis of skin tissue, based on photodissociation of oxyhemoglobin blood upon irradiation of the skin surface by a light beam, the wavelength of the radiation is chosen equal to 418±5 nm at a depth of generation of oxygen is less than 0.22 mm, the wavelength of the radiation is equal to 575±5 nm at a depth of generating oxygen from 0.22 mm to 0.9 mm, the wavelength of the radiation is equal to 585±5 nm at a depth of generation of oxygen 0.9 mm to 2.5 mm, and the wavelength of irradiation of 600±5 nm at a depth of generation of oxygen over 2.5 mm

The essence of the invention is illustrated by drawings, where: figure 1 shows the dependencies of the differential efficiencies of photodissociation (DEF), W/cm3(C) the depth z in the dermis by the irradiation of the surface of the skin at wavelengths 418 (curves 1), 575 (2), 585 (3) 600 (4) and 632.8 nm (5).

Figure 2 presents the values of the ratio r DEF the irradiation of the surface of the skin at wavelengths λ1=575 nm and λ=418 nm (curves 1), λ1=575 nm and λ=585 nm (2), λ1=575 nm and λ=600 nm (3) depending on the depth in the dermis.

We introduce the concept of differential effectiveness photodissociation DEF, which is defined as the number of oxygen molecules n(z, λ)generated per unit time per unit volume at depth z, the fall of a single the primary power density of the monochromatic light to the surface:

Here

z - depth in the dermis, measured from the surface of the skin;

µa(λ) is the spectral dependence of the absorption of oxyhemoglobin (1/cm);

H is the hematocrit (the volume concentration of erythrocytes in the blood);

f is the volume fraction of hemoglobin in erythrocytes;

Cv- volumetric concentration of the blood capillaries (the share of a unit volume of tissue occupied by capillaries);

S - the degree of oxygenation of the blood (the ratio of oxyhemoglobin to total hemoglobin);

q is the quantum yield for photodissociation (when illuminated with light in the visible range of the spectrum (λ≅300-650 nm) is approximately constant and is 3-5%, depending on temperature and other factors [5]);

E(z, λ) is the radiation density in the tissue,(W/m2), where I(λ, z, Ω) is the light intensity as a function of the angular coordinates ϑ and ϕ, dΩ=sin(ϑ)dϑdφ - elementary solid angle;

h=6.63·10-34J·s is Planck's constant;

c=3·1010cm/s is the speed of light.

In the formula (1) take into account that in the General case, the volume concentration of capillaries Cvmay depend on the depth z [6]. For concreteness below we assume typical values for the following parameters: N=0.4, f=0.25 according to the model [6].

We introduce the relation

shows how many times the DEF at a given depth z when the irradiation surface is expected at the wavelength of λ 1more (or less) of the corresponding value when irradiated at wavelength λ.

Relations (1) and (2) correspond to monochromatic light skin surface at wavelength λ1or λ. If for generation of oxygen used a light beam in the spectral range Δλ, then the formula (2) takes the form

Below will be proved that we have found wavelengths λ1(or ranges of wavelengths λ1±Δλ1), independent of z, which are the maximum values of DEF at specified depths in the thickness of the dermis, or, in other words, when the fixed z are r(z, λ1, λ)>1 and r*(z, λ1, λ)>1 for λ1≠λ.

Values defined by the formulas (1)to(3), depend, through the irradiance E(z, λ), from the structural, biophysical and optical characteristics of all layers of the skin - horn, epidermis and dermis. Further calculations using the model of the skin [7].

Figure 1 illustrates the underlying structure DEF at multiple wavelengths - 418 (curves 1), 575 (2), 585 (3), 600 (4) and 632 nm (5). These data are shown if the concentration of melanin in the epidermis fm=0.04, the thickness of the stratum corneum ds=20 μm and epidermis de=100 μm, Cv=0.04 and S=0.75. The power density of the irradiation surface E0=1 W/cm2. As can be seen from the graphs, when different Velich is nah z the most effective different wavelengths. In the upper layers of the dermis maximum photodissociation HbO2causes blue light with λ=418 nm. With increasing z the most effective wavelengths are sequentially shifted into the red area of the spectrum: in the range of 0.22 mm≤z≤0.9 mm is - λ=575 nm, 0.9 mm≤z≤2.5 mm λ=585 nm, at z≥2.5 mm-λ=600 nm. The boundary values of these depths is depicted in figure 1 vertical dashed straight. Our calculations (figures not shown) with other structural and biophysical parameters fabrics, typical of human skin [7], changing in the range of 15 μm≤ds≤25 microns, 0.02≤fm≤0.08, 60 μm≤de≤120 μm, 0.02≤Cv≤0.06, 0.5≤S≤0.97, and when Δλ=±5 nm relative to the wavelength λ, showed that the position of the boundaries, where the most effective one or the other wavelength, resistant to change dsfmdeCvand S. Thus, the coordinates of the depth can vary in a very narrow range - 0.22±0.02, 0.9±0.05 2.5±0.1 mm, This allows the use of these wavelengths 418, 575, 585 and 600 nm for the generation of molecular oxygen in the respective intervals of depths in the dermis. From the data of figure 1, it follows that the irradiation at a wavelength of 632.8 nm (prototype) is less effective at any depth from the point of view of raising the level of O2in the dermis compared to 418, 575, 585 and 600 nm. In other words, the irradiation of the surface of the skin at a wavelength of 418 nm in the dermis is formed of a CR is about 5-50 times lower molecular oxygen compared with radiation at these wavelengths 418, 575, 585 and 600 nm in the respective depth intervals z.

Figure 2 illustrates the dependence of the ratio r from the depths, as λ1selected 575 nm. Here also the boundary values of the above mentioned depth shows a vertical dashed straight. Shown in figure 2 the results allow us to estimate how many times more effective wavelengths 418, 575, 585 and 600 nm for excitation, photodissociation of oxyhemoglobin and increase the level of molecular oxygen in the tissue at the corresponding depths in the dermis.

Sources of information

1. Q.H.Gibson, S.Ainsworth. Photosensitivity of heme compounds // Nature. 1957. V.180. No.4599. P.1416-1417.

2. IMO, Ramazanov, Mr Anatoly Rubinov. The method of photodynamic therapy of cancer. Patent UA 82211 C2. A61N 5/06. Publ. 25.03.2008. Offic. bull. "Industrial property". Book 1. 2008. No. 6.

3. IMO, Ramazanov, Mr Anatoly Rubinov. The way to increase the local concentration of oxygen in biological tissues of the patient. The patent BY No. 9855 C1. 30.10.2007.

4. IMO, Angiolini, Ananstacia. Kinetics of oxygenation of skin tissue under the influence of low-intensity laser radiation // Ukr. go active. spectrosc. 2007. T. No. 1. S-125.

5. Svitashev, Nowlow, B.m.dzhagarov. A study by laser kinetic spectroscopy of bimolecular reaction stages oxygenation of α - and β-subunits of human hemoglobin in the R-state is // Biochemistry. 2003. T. No. 5. S-685.

6. Evegeni. Simulation Monte Carlo reflectance spectra of random multi-layer multiple-scattering and light-absorbing media // Quantum electronics. 2001. T. No. 12. S-1107.

7. Bun, Apiano, Avivausa, V.s.ulaschik. Absorption spectra and the penetration depth of light in normal and pathological human skin // Journal of applied spectroscopy. 2007. T. No. 3. S-394.

The way local increase of the concentration of molecular oxygen in the dermis of skin tissue, based on photodissociation of oxyhemoglobin blood upon irradiation of the skin surface by a light beam, characterized in that to determine the depth of location of the pathological area of the dermis at a depth of less than 0.22 mm, the irradiation light beam is carried out at a wavelength of equal to 418±5 nm, at a depth of from 0.22 mm to 0.9 mm irradiation carried out at a wavelength of 575±5 nm, at a depth of 0.9 mm to 2.5 mm irradiation carried out at a wavelength of 585±5 nm, and at a depth of more than 2.5 mm, the irradiation is carried out at a wavelength of 600±5 nm.



 

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1 ex

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4 cl, 13 dwg

FIELD: medicine.

SUBSTANCE: method involves building tunnel to posterior eyeball pole in inferoexterior and superexterior quadrants. The tunnel is used for implanting flexible polymer magnetolaser implant to the place, the subretinal neovascular membrane is localized. The implant has a permanent magnet shaped as a cut ring and is provided with drug delivery system and a short focus scattering lens of laser radiator connected to light guide. The permanent implant magnet is axially magnetized and produces permanent magnetic field of 5-7 mTesla units intensity. It is arranged with its north pole turned towards sclera at the place of the subretinal neovascular membrane projection with extrascleral arrangement of laser radiator lens membrane being provided in the subretinal neovascular membrane projection area. The other implant end is sutured to sclera 5-6 mm far from the limb via holes made in advance. The implant is covered with conjunctiva and retention sutures are placed thereon. Light guide and drug supply system lead is attached to temple with any known method applied. Drugs are supplied via the implant drug supply system in retrobulbary way in any order. Triombrast is given in the amount of 0,4-0,6 ml and dexamethasone or dexone in the amount of 0,4-0,6 ml during 3-4 days every 12 h. 0.1-1% aqueous solution of khlorin is intravenously introduced at the third-fourth day after setting the implant as photosensitizer, selected from group containing photolon, radachlorine or photoditazine, at a bolus dose of 0.8-1.1 mg/kg. Visual control of subretinal neovascular membrane cells fluorescence is carried out by applying fluorescent diagnosis methods. After saturating the subretinal neovascular membrane with the photosensitizer to maximum saturation level, intravitreous, transretinal laser radiation of 661-666 nm large wavelength is applied at general dose of 30-120 J/cm2. The flexible polymer magnetolaser implant is removed and sutures are placed on conjunctiva. Permanent magnet of the flexible polymer magnetolaser implant is manufactured from samarium-cobalt, samarium-iron-nitrogen or neodymium-iron-boron system material. The photosensitizer is repeatedly intravenously introduced at the same dose in 2-3 days after the first laser radiation treatment. Visual intraocular neoplasm cells fluorescence control is carried out using fluorescent diagnosis techniques. Maximum level of saturation with the photosensitizer being achieved in the subretinal neovascular membrane via laser light guide and implant lens, repeated laser irradiation of the subretinal neovascular membrane is carried out with radiation dose of 30-60 J/cm2.

EFFECT: accelerated subretinal edema and hemorrhages resorption; regression and obliteration of the subretinal neovascular membrane; prolonged vision function stabilization.

6 cl

FIELD: medicine.

SUBSTANCE: method involves filling vitreous cavity with perfluororganic compound. Two electrodes manufactured from platinum group metal are intravitreally, transretinally introduced into intraocular neoplasm. Electrochemical destruction is carried out with current intensity of 10-100 mA during 1-10 min in changing electrodes polarity and their position in the intraocular neoplasm space, and the electrodes are removed. 0.1-1% aqueous solution of khlorin as photosensitizer, selected from group containing photolon, radachlorine or photoditazine, is intravenously introduced at a dose of 0.8-1.1 mg/kg. Visual control of intraocular neoplasm cells fluorescence is carried out by applying fluorescent diagnosis methods. After saturating the intraocular neoplasm with the photosensitizer to maximum saturation level, intravitreous, transretinal laser radiation of 661-666 nm large wavelength is applied at a dose of 30-120 J/cm2 in perfluororganic compound medium. The transformed retina and tumor destruction products are intravitreally removed with perfluororganic compound volume being compensated with its additional introduction. Boundary-making endolasercoagulation of retinotomy area is carried out. The perfluororganic compound is substituted with silicon oil. The operation is ended in placing sutures over sclerotmy areas and over conjunctiva. Perfluormetylcyclohexylperidin, perfluortributylamine or perfluorpolyester or like are used as the perfluororganic compound for filling vitreous cavity. Platinum, iridium or rhodium are used as the platinum group metals.

EFFECT: complete destruction of neoplasm; reduced dissemination risk.

6 cl, 12 dwg

FIELD: medicine, applicable for stopping of pains of various nature.

SUBSTANCE: the device has a quantum-mechanical oscillator located in a casing, magnet, vessel for medicinal agent and a hollow cylinder. The magnet is installed between the oscillator and the vessel. Positioned in the vessel is a hollow cylinder having through holes on its surface.

EFFECT: quick and absolute anestesia.

2 ex, 1 dwg

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