RU2294223C2 - Method for biotissue phototreatment at induction of selective apoptosis - Google Patents

Abstract

FIELD: phototreatment of alive biotissue.

SUBSTANCE: it is necessary to fulfill phototreatment of biotissue that contains certain part with chromophore performed due to light-induced cell apoptosis of this part of biotissue that leads to its atraumatic modification, to removal, as well. The innovation deals with irradiating biotissue with light radiation at wave length ranged 500-2500 nm at density of energy being insufficient for destruction, but sufficient for inducing cell apoptosis of chromophore-containing biotissue. The innovation enables to perform phototreatment for inhibiting the growth of unfavorable hair, removing vascular defects and cutaneous pigment spots, remodeling the skin, reducing sebaceous glands in case of acne, removing neoplasms, reducing and removing hypertrophic and keloid cicatrices at induction of light-induced cell apoptosis of these parts of biotissue. Moreover, the innovation enables to carry out modification, the removal of biotissue atraumatically, without any cosmetically unacceptable complications, as well.

EFFECT: higher efficiency of phototreatment.

22 cl, 3 dwg, 7 ex, 3 tbl

Description

Technical field

This invention relates to photoprocessing of living biological tissue, causing light-induced apoptosis, leading to atraumatic modification, including the removal of certain parts of living biological tissue.

State of the art

Light radiation from lamps, lasers, and light emitting diodes is widely used in modern medical and cosmetic practice for surgical photo-processing of living biological tissue containing chromophores - substances of natural or artificial origin that have a high absorption coefficient of light radiation. Photoprocessing leads to selective photodegradation or photothermolysis due to pulsed light radiation (Anderson, R.R. et al., "Selective Photothermolysis: Precise Microsurgery by Selective Absorption of Pulsed Radiation", Science 1983, 220: 524-527). Selective photothermolysis is used in cases where the biological tissue contains chromophore-containing parts that are subject to destructive modification or removal, for example, such as vascular defects, pigmented lesions, unwanted hair. For selective photothermolysis, the wavelength of light radiation is selected based on the spectral range of the maximum absorption of the chromophore, while the pulse duration does not exceed the thermal relaxation time of the chromophore-containing part of the biological tissue, and the power density is selected sufficient for heating and coagulation. In this case, the destruction of this part of the biological tissue is achieved without light damage to the rest of the chromophore-free biological tissue.

Being clinically effective in solving problems of modifying or removing certain parts of a biological tissue, selective photo-processing has several disadvantages. Cell death due to the action of external damaging factors takes place according to the necrotic scenario, which, as you know, means a violation of the integrity of the cell membranes and the removal of intracellular contents into the intercellular space. This, of course, is accompanied by the formation of a local inflammatory process. In the area of the inflammatory reaction, nearby healthy parts of the biological tissue may also be involved, which is more likely to lead to side effects and complications. Clinically, these side effects and complications are manifested in the form of dyschromia, blisters, purpura, scarring, general discomfort due to pain. These side effects and complications are especially undesirable in cases where the requirements for a cosmetic result are increased, for example, when treating the skin in dermatology and cosmetology (CA Nanni, TS Alster, "Complications of Cutaneous Laser Surgery", Dermatologic Surgery, 1998; 24: 209- 219, B. Greve, C. Raulin, "Professional Errors Caused by Laser and Intense Pulsed Light Technology in Dermatology and Aesthetic Medicine: Preventive Strategies and Case Stadies", Dermatologic Surgery 2002; 28: 156-161). Side effects and complications associated with thermonecrosis of cells and tissues cause not only moral, but also material harm to patients, since they increase the total cost of treatment and lead to the loss of working time by socially active patients.

Thus, there is a need for an atraumatic and less costly method of clinically effective selective photo-processing of living biological tissue for the purpose of its modification, including removal, especially in cases associated with increased requirements for a cosmetic result.

SUMMARY OF THE INVENTION

The aim of the present invention is to provide such a method of photo-processing, in which it is possible to obtain a radical clinical result atraumatic and less expensive compared to selective photothermolysis.

The present invention is based on the discovery that, under certain conditions, apoptosis of vitally important cells of this biological tissue can be induced in a living chromophore-containing biological tissue when it is irradiated with light, a form of “soft” physiologically natural cell death in which cells are actively involved in their destruction. The process of apoptotic cell death, in contrast to necrosis during tissue destruction, takes place without inflammation. Thus, such a photoprocessing of living biological tissue becomes possible in which modification, including the removal of certain parts of it, can occur atraumatically.

In accordance with the method disclosed in the present invention, a biological tissue containing a specific part with a chromophore is irradiated with light radiation with a wavelength of 500 nm to 2500 nm, with an energy density insufficient for destruction, but sufficient to induce cell apoptosis of this part of the biological tissue. The ratio of apoptosis-inducing power density of light radiation to destructive includes a range from 45% to 90%. The ratio of apoptosis-inducing pulse duration to destructive one includes a range from 10% to 90%, depending on the time of thermal relaxation of the biological tissue.

In accordance with other methods disclosed in the present invention, biological tissue is irradiated for the purpose of inhibiting unwanted hair growth, removing vascular defects and age spots, skin remodeling, reduction of sebaceous glands in acne, removal of neoplasms, reduction, including removal of hypertrophic and keloid scars with an energy density insufficient for destruction, but sufficient to induce apoptosis of cells of these parts of the biological tissue.

Since there are no signs of inflammation with light-induced apoptosis, the photoprocessing methods disclosed in the present invention allow modification, including biological tissue removal is non-invasive, without cosmetically unacceptable complications.

Brief Description of the Figures

Figure 1 - dependence of the temperature T of apoptosis and destruction on the duration of isothermal exposure t _e . The shaded area indicated by the arrow corresponds to the degree of thermal damage Ω = 0.05-0.1 (apoptosis); the dashed line indicated by the arrow corresponds to the degree of thermal damage Ω = 1 (destruction).

Figure 2 - dependence of the ratio P _a / P _{d of the} apoptosis-inducing power density P _a to the destructive power density P _d on the pulse duration of light radiation t _p . The shaded area indicated by the arrow corresponds to the degree of thermal damage during apoptosis Ω _a = 0.05-0.1.

Figure 3 - dependence of the ratio t _pa / t _{pd of the} apoptosis-inducing pulse duration t _pa to the destructive pulse duration t _pd from the thermal relaxation time t _r . The areas indicated by arrows correspond to the degree of thermal damage during apoptosis Ω _a = 0.05-0.1: the shaded area in the upper part of the graph for “short” pulses t _pd / t _r <10 ^-1 , the shaded area in the lower part of the graph for “long” pulses t _pd / t _r > 10, the region between the upper and lower shaded areas for pulses, the duration of the order of the thermal relaxation time 10 ^-1 <t _pd / t _r <10.

Detailed Disclosure of Invention

The energy of light radiation absorbed in the chromophore gives rise to a number of stress factors for cells. Plastic deformation of the cells by an elastic acoustic wave propagating from the chromophore to the cells during the photomechanical conversion of absorbed energy is possible. Photochemical conversion can lead to the appearance of free radicals or, for example, to the breaking of bonds in DNA upon UV irradiation. From the point of view of the present invention, of particular interest is the thermal stress factor, which dominates at a wavelength of light radiation exceeding 500 nm, and is due to heat transfer from the chromophore to cells during photothermal conversion of the energy absorbed in the chromophore. In the sublethal region, i.e. potentially, but not necessarily destructive, temperatures, there is a certain range of temperatures at which apoptotic death prevails over coagulation (NP Matylevitch et al., "Apoptosis and Accidental Cell Death in Cultured Human Keratinocytes After Thermal Injury", American Journal of Pathology 1998, 153 : 567-577, H.-KB Dihn et al., "Gene expression profiling of the response to thermal injury in human cells", Physiol Genomics 2001, 7: 3-13), in the presence of appropriate physiological regulatory factors in the biological tissue itself.

The idea underlying the present invention is that light radiation, with certain optical characteristics, can serve as an inducer of apoptosis, since the apoptosis-inducing sublethal temperature can be due to the heat released during the photothermal conversion of the energy of light radiation absorbed in the chromophores of this biological tissue.

The temperature values at which thermocoagulation predominantly occurs are from about 50 ° C at temperature exposures of about 100 ° C and above 100 ° C with a decrease in exposure to the microsecond range (D. Simanovski et al., "Cellular tolerance to pulsed heating", SPIE Proc, BIOS 2005, v. 5695, pp. 1-6). From the point of view of the present invention, complete thermonecrosis and apoptosis should be separated by a sufficiently wide temperature range, in the presence of appropriate physiological mechanisms in the cells. In this case, it is possible to realize preferential apoptosis without significant thermocoagulation, i.e. the degree of thermocoagulation for apoptosis-inducing temperatures should not exceed 10%. For example, isothermal exposure of keratinocytes lasting 1 s at a temperature of about 64 ° C leads to their thermocoagulation. Apoptosis is induced primarily upon reaching a temperature of 56-58 ° C at the same exposure. Based on experimental data approximated by solutions of the Arrhenius equation:

Where:

E ₀ - coagulation activation energy (JM ^-1 );

R is the universal gas constant (JM ^-1 K ^-1 );

A is the frequency factor (s ^-1 );

t _e is the duration of the temperature exposure (s);

T (t) is the temperature of the biological tissue (K);

 Ω is the degree of thermal damage (fraction);

in the isothermal approximation and shown in FIG. 1 and Table 1, there corresponds a region (indicated by an arrow, shaded in FIG. 1) with insignificant thermocoagulation within the range of values from 5 · 10 ^-2 to 10 ^-1 , in which the concentration of coagulated cells is from 5% to 10%, respectively. Apoptosis-inducing temperatures include a range from 43 ° C to 145 ° C at appropriate times of temperature exposure t _e , providing a sublethal character of stress. The approximation of “isothermality,” in this case, means that during exposure, the temperature (ie, the effect of heat on keratinocytes) can be considered constant.

Table 1
Values of temperatures T leading to the degree of thermal damage Ω = 0.05-0.1 (apoptosis) and Ω = 1 (destruction) depending on the duration of the isothermal exposure t _e t _e , s  Ω, share 1,0 0.1 0.09 0.08 0,07 0.06 0.05 ^10-10 145.5 135.6 135.2 134.7 134.2 133.5 132.8 10 ^-9 135.6 126.2 125.8 125.3 124.8 124.2 123,4 10 ^-8 126.2 117.2 116.8 116.3 115.8 115,2 114.5 10 ^-7 117.2 108.6 108,2 107.7 107.3 106.7 106.0 10 ^-6 108.6 100.3 99.9 99.5 99.1 98.5 97.9 10 ^-5 100.3 92.4 92.1 91.7 91.2 90.7 90.1 10 ^-4 92.4 84.8 84.5 84.1 83.7 83,2 82.6 10 ^-3 84.8 77.6 77,2 76.9 76.5 76.0 75,4 10 ^-2 77.6 70.6 70.3 69.9 69.5 69.1 68.5 10 ^-1 70.6 63.9 63.6 63.3 62.9 62,4 61.9 one 63.9 57.4 57.2 56.8 56.5 56.0 55.6 10 57.4 51,2 51.0 50.6 50.3 49.9 49.4 10 ² 51,2 45.3 45.0 44.7 44,4 44.0 43.5

At a lower degree of thermocoagulation, the increased activity of heat shock proteins — chaperone molecules — whose concentration in cells subject to moderate heat stress is about 5-10%, dominates. Due to the activity of chaperones, cell activity is restored in the event of moderate heat stress (J.T. Beckham et al., "Assessment of Cellular Response to Thermal Laser Injury Through Bioluminescence Imaging of Heat Shock Protein 70", Photochemistry and Photobiology 2004, 79: 76-85). It is also possible cell aging with arrest (C. Soti et al., "Apoptosis, necrosis and cellular senescence: chaperone occupancy as a potential switch", Aging Cell 2003, 2: 39-45), but not its apoptosis.

The temperature of the biological tissue, and hence the degree of thermocoagulation of the biological tissue during photothermal conversion, depends on the values of power density (W / cm ² ) and pulse duration (s) of light radiation. From the point of view of the present invention, of particular interest is the comparison of apoptosis-inducing and destructive power densities and pulses of light radiation. In the general case, the value of the power density can change during the pulse due to changes in power characteristic of a particular type of light source due to the characteristics of generation. In this case, we should talk about instantaneous power, i.e. power at a given time. For example, the value of instantaneous power can linearly increase from zero at the beginning to the maximum towards the end of the pulse, forming sawtooth pulses. Another case is when the instantaneous power is maximum at the beginning of the pulse and drops to zero towards the end, as in the case of the glow of flash lamps powered by capacitors. Nevertheless, in practice, any pulse shape is approximated rectangular, with some effective or averaged power value, constant during the pulse, if we are not talking about special problems concerning the features of the photothermal conversion of light radiation having one or another given pulse shape. In the case of rectangular pulses, the power density and pulse duration determine the energy density of light radiation by the following expression:

Where:

E is the energy density of light radiation (J / cm ² );

P is the power density of light radiation (W / cm ² );

t _p - pulse duration of light radiation (s).

We can compare the apoptotropic and destructive values of the power density and the duration of rectangular pulses by solving the Arrhenius equation for cases of complete thermal damage (at Ω = 1) and for the apoptotinducing region (Ω = 5 · 10 ^-2 -10 ^-1 ). The dependence of the temperature of the biological tissue on the power and duration of a rectangular pulse of light radiation during photothermal energy conversion is known from the solutions of the equations of light propagation and heat transfer and can be represented in the following generalized form:

Where

t _p, P are defined above;

t _r is the thermal relaxation time of the biological tissue (s) defined by the expression t _r ≅d ² / kα, in which d is the characteristic size of the chromophore-containing part of the biological tissue (cm), α is the thermal diffusion coefficient of the biological tissue (cm ² s ^-1 ), k is geometric factor; light emission pulses are considered “long” at t _p ≫t _r and “short” at t _p ≪t _r ;

зависящий от оптических и геометрических параметров биоткани;K - coefficient

depending on the optical and geometric parameters of biological tissue;

T ₀ - physiologically normal temperature of the biological tissue

Thus, the ratio of apoptosis-inducing and destructive power densities at a given pulse duration will be determined by the following expression:

Where:

P _a is the apoptosis-inducing power density (W / cm ² );

P _d - destructive power density (W / cm ² );

Ω _a - the degree of thermal damage during apoptosis (fraction);

Ω _d - the degree of thermal damage during destruction (fraction),

usually taken Ω _d = 1;

E ₀ , R, A, t _p , E ₀ are defined above.

In Fig.2 and in Table 2, the values of the ratio of power densities P _a / P _d for Ω _a = 5 · 10 ^-2 -10 ^-1 (the shaded area indicated by the arrow in Fig. 2) are shown depending on the specified pulse durations, from which it can be seen that the ratio of apoptosis-inducing and destructive powers decreases from 90% to 45% with increasing pulse duration. In this approximation, the ratio P _a / P _d is independent of the ratio of the pulse duration and the thermal relaxation time of the biological tissue. Thus, the apoptosis-inducing and destructive power densities are separated by rather wide, from the point of view of practical applications, intervals of values.

table 2
The values of the ratios P _a / P _{d of the} apoptosis-inducing power density P _a to the destructive power density P _d depending on the pulse durations t _p for different values of the degree of thermal damage during apoptosis Ω _a t _p, s Ω _a , share 0.1 0.09 0.08 0,07 0.06 0.05 ^10-10 0,909 0,905 0,900 0.895 0.889 0.882 10 ^-9 0.904 0,900 0.895 0.890 0.884 0.876 10 ^-8 0.899 0.894 0.889 0.884 0.877 0.870 10 ^-7 0.892 0.888 0.882 0.876 0.869 0.861 10 ^-6 0.885 0.880 0.874 0.867 0.860 0.851 10 ^-5 0.875 0.870 0.863 0.856 0.848 0.839 10 ^-4 0.863 0.857 0.850 0.843 0.834 0.823 10 ^-3 0.848 0.841 0.834 0.825 0.815 0.804 10 ^-2 0.828 0.820 0.812 0.802 0.791 0.778 10 ^-1 0,800 0.791 0.781 0.777 0.757 0.742 one 0.760 0.750 0.737 0.724 0.708 0.690 10 0.696 0.683 0.668 0.650 0.631 0,607 10 ² 0.580 0.561 0.540 0.516 0.489 0.457

The ratio of apoptosis-inducing and destructive pulse durations for a given power density of light radiation will be determined by the following expressions:

in the case of "long" pulses:

и

and

in the case of "short" pulses:

Where:

t _pa - pulse duration during apoptosis (s);

t _pd is the pulse duration at complete destruction (s);

E ₀ , R, T ₀ , A, Ω _a , Ω _d are defined above.

In most practical applications, the pulse durations are correlated with the thermal relaxation time, therefore, Fig. 3 and Table 3 show the values of the ratio of the pulse durations t _pa / t _pd depending on the thermal relaxation time t _r at Ω _a = 5 · 10 ^-2 -10 ^-1 for "short" (t _pd / t _r <10 ^-1 , the shaded area indicated by the arrow in the upper part of the graph of Figure 3) and "long" (t _pd / t _r > 10, the shaded area indicated by the arrow in the bottom of the graph Figure 3) pulses. As can be seen from Figure 3 and Table 3, the ratio t _pa / t _pd strongly depends on the ratio of the pulse duration t _pd and the thermal relaxation time t _r . Apoptosis-inducing pulse durations are from 5-10% to 75-90% of the destructive power of light radiation at a given density in the region of "long" and "short" pulses, respectively. Thus, apoptosis-inducing and destructive pulse durations are also separated by rather wide, from the point of view of practical applications, intervals of values.

In the region of "short" pulses, apoptosis is induced with a decrease in pulse duration at a constant power density in approximately the same proportion as when a decrease in power at a constant pulse duration (see Figure 2 and Table 2) by 10-30%. In the region of “long” pulses, the sensitivity to a change in power compared to a change in the pulse duration is much higher. Physically, this is due to the fact that with “long” pulses a quasi-stationary from the point of view of time thermal balance is established between the heat released during the absorption of light in the chromophore-containing part of the biological tissue and the heat dissipated into the surrounding biological tissue. In this case, the steady-state temperature depends mainly on the power, and not on the pulse duration, in contrast to “short” pulses, in which there is no heat dissipation into the surrounding biological tissue and the temperature depends equally on the power and on the pulse duration.

"Long" pulses may be applicable in cases where thermal diffusion into the surrounding tissue is acceptable in accordance with the objectives of photo processing. For example, when irradiating a cell culture having an estimated thermal relaxation time of a few milliseconds with light pulses lasting from the second range, to provide an isothermal condition. However, in most cases of photoprocessing, pulse durations of no more than an order of magnitude more than the thermal relaxation time are of particular interest (the values t _pa / t _pd indicated by the arrows falling between the shaded areas of the graph in FIG. 3).

Table 3
The ranges of ratios t _pa / t _{pd of} apoptosis-inducing pulse durations t _pa and destructive pulse durations t _pd , corresponding to the degree of thermal damage during apoptosis Ω _a = 0.05-0.1, depending on the thermal relaxation time t _r at different ratios of the destructive pulse duration t _pd with thermal relaxation time t _r t _pd / t _r t _r , s 10 ^-5 10 ^-4 10 ^-3 10 ^-2 10 ^-1 one 10 one hundred <10 ^-1 0.91-0.86 0.9-0.85 0.89-0.84 0.88-0.82 0.87-0.8 0.86-0.77 0.85-0.73 0.84-0.68 10 ^-1 -10 0.86-0.1 0.85-0.1 0.84-0.1 0.82-0.1 0.8-0.1 0.77-0.1 0.73-0.1 0.68-0.1 > 10 0.05-0.1

Thus, taking into account that the product of the power density and pulse duration determines the energy density of light radiation, we can conclude that the apoptosis-inducing energy density of light radiation during photo processing can be from 10% to 90% of the energy density that causes tissue destruction due to thermonecrosis.

In the clinical practice of photoprocessing, which is largely related to the individual characteristics of pathologies, it is impossible to theoretically predict the required parameters of light radiation with the necessary accuracy. Therefore, as a rule, the estimated ranges of parameters are followed, and then, after point test exposures, the parameters of light radiation are set for the selected type of processing and final goals. From the point of view of practical implementation of the present invention, known clinical signs characteristic of the response of living biological tissue to lethal damage, for example, edema, erythema, can be used as a criterion for choosing the required power density. To obtain light-induced apoptosis in accordance with the present invention, an energy density, i.e. power density and / or pulse duration should be reduced until these signs disappear. Then you must additionally either reduce the power density, within 10-55%, with a constant pulse duration in accordance with Figure 2 and Table 2, or reduce the pulse duration by 10-95% with a constant power density in accordance with Figure 3 and Table 3.

The ratios of apoptosis-inducing and destructive temperatures, power densities, and pulse durations for different types of biological tissue and cells may differ. These differences are due to the nature of temperature sensitivity, which is reflected including and on the values of the frequency factor A and the activation energy of coagulation E ₀ , which can take values in the ranges 10 ⁵ -10 ⁶ JM ^-1 and 10 ⁴⁰ -10 ¹⁰⁵ s ^-1 , respectively (J. Pearce, S. Thomsen, "Rate process analysis of thermal damage ", Optical-Thermal Response of Laser Irradiated Tissue, AJ Welsh and MJC van Gemert, eds., Plenum, New York, 1995, pp. 561-606), depending on the type of biological tissue. However, the pattern will remain the same and serves as a criterion for assessing the difference that exists in the values of the power and duration of light radiation pulses that provide photothermolysis and light-induced apoptosis.

Since temperature is only one of the physical factors leading to the induction of apoptosis, and there are other potentially apoptotic inducing factors, chemical or mechanical, which are manifested in the photochemical or photomechanical interaction of light radiation with biological tissue, the method of light inducing apoptosis disclosed in the present invention can be expanded accordingly considering these factors. Light-induced apoptosis is possible in the entire spectral range used for selective photoprocessing of living biological tissue.

From the point of view of changes in biological tissue immediately after irradiation, apoptosis, in contrast to necrosis, in most cases is not fixed by known methods, i.e. the tissue remains the same as before irradiation. The process of apoptotic cell death occurs hours after irradiation and can last for weeks.

High-resolution 40-100 MHz high-resolution ultrasound scanning (G. Czarnota et al., "Ultrasound Imaging of Apoptosis", Methods in Molecular Biology, v.203, 2002, pp. 257-277, G) can be used for operational non-invasive monitoring of apoptosis. . Czarnota et al., "Ultrasound imaging of apoptosis: high-resolution non-invasive monitoring of programmed cell death in vitro, in situ and in vivo", Br J Cancer. 1999 Oct; 81 (3): 520-527). Apoptosis is characterized by a series of specific morphological changes in the cell, other than necrosis, and several times increasing the ultrasound scattering intensity and echogenicity, both in comparison with normal biological tissue and in comparison with necrotic tissue. Consequently, the appearance on the ultrasound image of the biological tissue of areas with increasing diffuse brightness with a decrease in the energy parameters of light radiation from lethal to sublethal means, with the highest degree of probability, initiation of apoptosis, if any other changes in biological tissue are not expected, usually leading to an increase in intensity Ultrasound scattering. The depth of such an ultrasound scan is usually limited to 3-5 mm, but often this is quite enough, for example, for dermatological and cosmetic applications.

Biotissue irradiation can be carried out not only in single-pulse, but also in multi-pulse modes used to prevent unwanted heating of parts of the biological tissue with competing chromophores that are not subject to exposure, but fall into the irradiation field.

The spectral range of light radiation considered in the present invention has an upper limit with a wavelength of 2500 nm due to the strong absorption of interstitial water above this value, which accordingly limits the selectivity of the effect. Nevertheless, the emergence of tasks requiring photoprocessing, which induces apoptosis to a depth estimated by one or more cell layers, for example, with surface treatment of cell cultures with erbium (2900 nm) or CO ₂ (10600 nm) lasers, is not ruled out. There are no fundamental reasons why the present invention could not be applied in these cases.

Biological tissue can be irradiated both interstitially and transversely. Interstitial, including intravascular, irradiation is advisable for the deep localization of the exposed cells, for example, adipocytes of adipose tissue, osteoblasts of bone tissue or blood cells. Interstitial irradiation can be carried out using thin optical fibers, including in a reinforcing metal sheath, introduced into the biological tissue using injectors, similar to the introduction of needles. If the biological tissue to be affected is localized not deeply, such as the basal layer of the skin or limited to the optically transparent part of the biological tissue, such as the vitreous body of the eye, then it is advisable (in cases when it is technically possible) to perform transverse irradiation. The concept of transverse irradiation of the present invention also includes irradiation through the surface of internal cavities, for example, during endoscopic interventions using appropriate technical means.

For transverse irradiation, it may be necessary to remove heat from the surface through which the irradiation is performed, for example, when the absorption of chromophores is not strong enough. The heat can be removed in various ways, for example, by blowing with cold air, applying a rapidly evaporating coolant to the surface of the biological tissue, including in the form of an aerosol, by contacting a thin optically transparent plate from a material with relatively high thermal conductivity, for example sapphire, if necessary forcibly cooled, for example, thermoelectric element, coolants or by blowing a stream of gas. This plate is applied to the skin surface and light radiation is passed through it into the biological tissue during irradiation. To improve the optical and thermal contact between the surface of the biological tissue and the plate, the surface of the biological tissue or plate can be moistened with an optically transparent liquid or gel. This plate, in cases, for example, when hemoglobin turns out to be a competing chromophore, can be applied with some pressure to the biological tissue to achieve a compression effect in which blood is forced out of the vessels located in the irradiation zone. This plate, with refractive index and scattering coefficients agreed with the biological tissue, can also serve to remove backscattered radiation from the biological tissue. Being selected sufficiently thin, the same plate, if necessary, can serve to introduce part of the reflected radiation back into the biological tissue due to total internal reflection on the inner face.

In many cases, especially during photoprocessing of biological tissue containing cyclically developing cells or cellular structures, it may be necessary to conduct multiple irradiation sessions of the same part of the biological tissue. In this case, when choosing a long-term treatment regimen, it is necessary to take into account the duration of the development cycle of these cells or structures. It is also necessary to take into account the duration of the apoptotic death process, which can range from days to weeks.

Chromophores of the present invention may include both natural and artificial. Examples of natural chromophores naturally produced in this part of the biological tissue are melanin, hemoglobin, water, lipids, protein, DNA, and cytochromes. Artificial chromophores are introduced into the tissue from the outside. Artificial chromophores can be, for example, solutions of dyes, suspensions of pigments, nanoparticles. These chromophores can be localized both inside and outside the cells to be exposed in accordance with the objectives of photo processing.

As sources of light radiation of the present invention, various types of coherent and incoherent emitters can be used: lasers, light emitting diodes, and visible and infrared lamps. The choice of this or that type of light source is determined by the length or range of wavelengths corresponding to the chromophores of the biological tissue, the duration of the pulses and the power necessary to achieve the results of photoprocessing due to apoptosis. Such lasers as, for example, argon (515 nm), potassium-titanium phosphate KTP (532 nm), dye (575-610 nm), ruby (694 nm), alexandrite (755 nm), diode (can be used) can be used. 810-1050 nm), neodymium (1064 nm), holmium (2100 nm) and other known types of lasers of continuous, free generation and Q-switched. Lamps, unlike lasers, are broadband light sources. The necessary wavelength range can be obtained by filtering the light radiation of xenon, mercury, halogen, and other known types of lamps, which after filtering can provide the necessary energy characteristics of light radiation. Single, point sources, as well as rulers and matrices from them, can be used.

Photoprocessing using induced apoptosis of cells of a part of a living biological tissue may be accompanied by stimulated biological activity of other components of this part of a biological tissue through apoptotic expression of cytokines, such as, for example, TGF-β, PDGF, FGF, IL-1β, TNF-α. The disclosed photoprocessing method with the induction of apoptosis can be used for various purposes, including hair removal and growth inhibition of unwanted hair, remodeling of the skin, blood vessels, bone and cartilage, removal of vascular defects, control of scarring, including inhibition of the growth of hypertrophic scars and keloids, removal of adipose tissue and sebaceous glands with acne, removal of skin neoplasms, including caused by an imbalance in apoptosis and cell proliferation, including due to apoptosis of the vascular cells of the blood vessels that feed these neoplasms. The present invention can be applied to the processing of tissues of plant origin and microorganisms, cell cultures of living biological tissues, including in scanning laser microscopy.

The difference of the method of the present invention from methods based on selective photodestruction consists in the possibility of achieving a clinically effective “soft” atraumatic modification, including the removal of a certain part of the biological tissue without the inflammatory reaction characteristic of previously known methods and the side effects and complications caused by this reaction. The absence of complications and side effects also reduces the total cost of treatment, including due to the saving of losses of working time by working patients. Since light induction of apoptosis requires 10-90% less light energy than with photodestruction, and therefore, the power of light sources and the cost of their production will be lower, the cost of equipment, the cost of its operation and, accordingly, the cost of treatment are reduced.

Examples of carrying out the invention

The following examples are not restrictive, but are intended to demonstrate the implementation of the invention.

Example 1. Inhibition of growth, including unwanted hair removal

Apoptosis is the central element that determines the cyclicality in the evolution of the follicle, since it is programmed to start at a certain time of growth, transferring the follicle from the growth phase to the resting stage. In accordance with the present invention, apoptosis of vital follicle cells including keratinocytes of the epithelium and vascular cells of the microvasculature supplying atrophy of the follicle or at least premature regression of the anagen follicle to the stage of catagen can be induced by non-damaging “soft” external light exposure. Premature from the point of view of the normal development of the follicle and controlled cyclic switching of the anagen follicle to the catagen stage allows one to inhibit the development of the follicle, which is consistent with the purpose of controlling the growth of unwanted hair. In contrast to the known methods of photoepilation due to destruction, in the present invention, the removal of vital cells and substructures occurs due to their physiologically natural atraumatic death.

A device layout was assembled, consisting of a head including a low-voltage 15 V / 10 A quartz halogen lamp (OSRAM) integrated into an ellipsoidal reflector coated with a reflective gold film and focusing light radiation through a thin quartz plate. Between this quartz plate and the lamp, filters were installed that cut off the short-wave and long-wave parts of the spectrum in such a way as to provide a spectral band from 500 nm to 1200 nm, in which the absorption of the main chromophore of the follicle - the hair shaft melanin is maximal. The lamp was controlled by a power source and a timer for setting the pulse duration from 0.5 to 3 s. Irradiation was carried out on the front of the leg with a skin type of II-III according to Fitzpatrick and a hair color from brown to ashen-brown with a hair density of 13 pcs / cm ² . A few minutes before irradiation, a 20 cm × 4.5 cm area was shaved so that the hair protruded 0.5-1 mm above the skin surface. A section of 16 cm × 4.5 cm was irradiated. The rest of the section (4 cm × 4.5 cm) was not subjected to photo processing and served as a control. The irradiated area, in turn, was divided into 4 quadrants 4 cm × 4.5 cm in size. A single irradiation was carried out on two adjacent quadrants, twice on the third, and three times on the fourth. The time interval between subsequent multiple exposures was 1 month. Immediately prior to irradiation, the skin was marked with a red marker and moistened with water. During irradiation, the head was tightly applied by a quartz plate to the skin surface with a slight pressure. To clarify the necessary parameters of light radiation, test irradiations were performed. An indicator of energy restriction was a sign of thermal damage to the follicle - perifollicular edema and loss of the hair shaft with the inner shell of the follicle with a light pull with tweezers immediately after irradiation.

On one of the quadrants intended for a single exposure, the energy density and exposure time were set so as to obtain a perifollicular edema, i.e. thermal damage to the follicle immediately after irradiation. For this type of hair and this skin area, the threshold power density at which perifollicular edema manifested was about 40 W / cm ² with a pulse duration of 1 s. In the remaining areas, irradiation was performed with a power density lower by 25% for the same pulse duration, i.e. 30 W / cm ² , in accordance with Figure 2 and Table 2. After setting the necessary parameters of light radiation, the entire skin area was exposed to a single exposure.

A few days later a weak prurigo was revealed in the irradiated area. Hair on the irradiated and control area began to appear simultaneously. However, after 1.5-2 weeks, mass hair loss began to be observed in the irradiated area and the difference between the control and irradiated areas became visually obvious. The falling hair was deprived of bulbs and their appearance on the surface was caused not so much by growth as by the displacement of hair “stumps” from shrinking follicles. After 4 weeks, up to 60% of hair grew in the control plot, while less than 20% of hair grew in the irradiated areas. Over time, this difference decreased, but by week 18 it stabilized at 100% and 80%, respectively. By week 28, i.e. after 6 months after photo-processing, no significant changes between the control and the treated area were observed. Considering that the cycle of hair growth on the lower leg is on average from 3 to 6 months, it can be concluded that 20% of the follicles died or, at least, their activity was stopped for a long time. If we further take into account that of all the hair on the lower leg at any time, about 20% is in the anagen, we can also conclude that these dead or stopped follicles were anagenic. The density of newly growing hair 5 months after double exposure decreased to 60%, 4 months after triple exposure - up to 50%, 3 months after four - up to 40%.

A diode laser with a wavelength of 810 nm, a power of up to 90 W, a pulse duration of 0.1 s to 1 s and a diameter of the light spot of 5 mm, providing a maximum power density of up to 450 W / cm ^{2 was also used} .

A few minutes before the irradiation, a 22 cm x 4 cm area with a hair density of 13 pcs / cm ^{2 was} shaved so that the hair protruded 0.5-1 mm above the skin surface. A section of 20 cm × 4 cm was irradiated. The rest of the section (2 cm × 4 cm) was not subjected to photo processing and served as a control. The irradiated area, in turn, was divided into 10 quadrants with a size of 4 cm × 2 cm. The average hair diameter was about 70 microns, with an estimated follicle thermal relaxation time of about 0.1 second. Irradiation was carried out through a precooled, precooled, optically transparent gel (usually used for ultrasound scanning) applied to the skin.

The threshold power density at which peripheral edema manifested was about 60 W / cm ² with a pulse duration of 1 s. For 5 out of 10 quadrants, a single exposure was performed with a power density of 60 W / cm ² , 50 W / cm ² , 45 W / cm ² , 40 W / cm ² and 35 W / cm ² with a fixed pulse duration of 1 s. In the remaining 5 quadrants, a single exposure was performed with a pulse duration of 1 s, 0.9 s, 0.7 s, 0.4 s, 0.1 s, with a fixed power density of 60 W / cm ² .

The decrease in power density below 40 J / cm ² and pulse durations below 0.4 s was clinically significant in terms of the density of newly growing hair, which was close to the control.

The desired effect in terms of the significance of differences from control was observed in the wavelength range from 500 nm to 1200 nm with power densities from 80% up to 70% and pulse durations from 80% up to 50% from destructive values of power density and pulse durations, respectively.

Example 2. Removal of vascular skin defects

Apoptosis of vascular cells, i.e. endothelial cells and vascular smooth muscle, is accompanied by an increase in pro-adhesive and coagulative properties, leading to the formation of a blood clot. In accordance with the present invention, apoptosis of vascular cells can be induced by non-damaging “soft” external light, leading to thrombosis and vascular atrophy of vascular pathologies, such as, for example, telangiectasias, angiomas, hemangiomas. Unlike the known photocoagulation methods, in the present invention, the removal of vascular defects is atraumatic.

In the model of the lighting device described in the above example, a filter was installed to provide a spectral band from 500 nm to 1200 nm, in which hemoglobins and water, the main chromophores in the blood of blood vessels, are absorbed quite strongly.

Irradiation was carried out on a face area with type II ÷ III skin according to Fitzpatrick measuring 5 cm × 10 cm with telangiectasia on the cheek in the form of vessels with a diameter of about 0.5 mm with an estimated thermal relaxation time of about 0.5-1 s. Immediately prior to irradiation, the skin was moisturized with water. The head of the light source during irradiation was applied by a quartz plate to the skin without pressure. A limitation of the power flow and exposure duration was the visual clarification of blood vessels, erythema and edema along the vessels immediately after the trial exposure. The pulse duration in this test irradiation was 1 s at a power density in the light spot of about 40 W / cm ² .

The power density and pulse duration were reduced to 40 W / cm ² at 0.6 s and 28 W / cm ² at 1 s. The first signs of visual clarification and the disappearance of blood vessels became noticeable 10 days after irradiation.

A diode laser was also used with a wavelength of 810 nm, a power density of 140 W / cm ² and 100 W / cm ² , with pulse durations of 0.3 s and 0.5 s, respectively.

The desired effect in terms of the significance of differences from the control was observed in the wavelength range from 500 nm to 1200 nm with power densities from 80% up to 70% and pulse durations from 80% up to 65% of destructive values of power density and pulse duration, respectively.

Example 3. Removal of age spots

Pigment spots are characterized by an excess of melanin in the form of melanosomes in keratinocytes and melanocytes, caused either by excessive production of melanin by melanocytes (e.g., solar lentigo, freckles, coffee macula), or by excessive proliferation of melanocytes (e.g., Ota nevi, Mongolian spots). In accordance with the present invention, apoptosis of excess melanosome-containing melanocytes and keratinocytes can be induced by non-damaging “soft” external light exposure, leading to lightening and reduction of pigmentation, up to the removal of the age spots. Unlike the known methods of photodegradation of age spots, in the present invention, their removal occurs atraumatically.

A neodymium laser with a Q-factor and frequency doubling with a pulse duration of 10 nanoseconds and a wavelength of 532 nm, on which melanin is highly absorbed, is the main source of light radiation, which is the main chromophore of pigment spots contained in melanosomes, the size and estimated thermal relaxation of which is about 1 microns and 0.5-1 microseconds, respectively. Irradiation was carried out on skin of type II-III according to Fitzpatrick with solar lentigo on the back. Edema and erythema in the area of the pigment spot immediately after the test irradiation served as a limiter to the power flux and exposure duration. The power flow during this test irradiation was 500 MW / cm ² with a pulse duration of 10 nanoseconds. The power density was reduced to 450 W / cm ² at the same pulse duration. Irradiation was carried out in successive sessions after 30 days each. The pigmentation index of the spot was measured with a Mexameter (Courage + Khazaka electronic, Germany). The first signs of lightening became noticeable 10 days after the second session.

In the above example, a pigment spot was considered as a set of thermally unrelated absorbing parts of biological tissue in the form of single melanosome-containing cells. With a permissible isotropic distribution of melanin and pulse durations exceeding the characteristic time of heat diffusion from one melanosome-containing cell to another, a pigment spot should be considered as a single part of the biological tissue with a certain thickness and the corresponding thermal relaxation time. In this case, the mechanism of apoptosis of other cells, including vascular cells localized between melanin-containing cells, can lead to remodeling of the tissue as a whole. This approach can, in principle, be generalized to other similar cases of the ratio of the pulse duration and the characteristic thermal diffusion time between the absorbing centers. From this point of view, a diode laser with a wavelength of 810 nm was used, at which melanin absorbs less than 532 nm, but strong enough for the photothermal effect to manifest. The thickness of the lentigo did not exceed 20 microns with an estimated thermal relaxation time of about 0.01 second. Results similar to those described above were obtained with thresholds for the destruction of power density of about 150 W / cm ² at a pulse duration of 0.02 s, then reduced to 150 W / cm ² at 0.015 s and 120 W / cm ² at 0.02 s.

The desired effect in terms of the significance of difference from control was observed in the wavelength range from 500 nm to 900 nm with power densities from 90% up to 70% and pulse durations from 90% up to 70% from destructive values of power density and pulse durations, respectively.

Example 4. Skin remodeling in premature aging

Premature aging of the skin due to exposure to ultraviolet radiation and other harmful factors and is characterized by a number of indicators, including premature wrinkles and loss of elasticity due to destruction of collagen fibers of the dermis, heterogeneity of pigmentation of the epidermis, and telangiectasia. In accordance with the present invention, apoptosis of epidermal keratinocytes and vascular cells of the papillary dermal vasculature of the dermis in the region of the basal layer can be induced by a non-damaging “soft” external light exposure. Apoptosis of keratinocytes and vascular cells is accompanied by the expression of cytokines that activate fibroblasts to collagenogenesis, matrix remodeling, neovascularization in the upper dermis and epidermal remodeling. Unlike the known methods of photodegradation of age spots, in the present invention, their removal occurs atraumatically.

A Fitzpatrick type II 50 mm × 50 mm face area was subjected to photoprocessing. Photo processing was carried out in several sessions with a time interval of 2 weeks.

The dermal subsapillary vasculature and epidermal basal keratinocytes were considered either as a set of thermally unrelated single absorbing keratinocytes and microvessels of about 10 micrometers in size with an estimated thermal relaxation time of about 1 ms, or as a single part of a biological tissue about 150-200 microns thick with an estimated thermal time relaxation of about 500-800 ms, significantly exceeding the characteristic time of thermal diffusion from one keratinocyte to another and from one microvessel to another. Accordingly, light sources were selected.

We used a KTP laser with a wavelength of 532 nm, which strongly absorbs hemoglobin and melanin - the main chromophores of vasculature and basal keratinocytes at this wavelength. Immediately prior to irradiation, the skin was moisturized with water. Edema and erythema of the skin immediately after trial exposure served as a limiter to the power flow and exposure duration. The power density in this test irradiation was about 4000 W / cm ² with a pulse duration of 2 ms. The power density and pulse duration were reduced to 3200 W / cm ² at 2 ms and 4000 W / cm ² at 1.5 ms. The skin elasticity and wrinkle profile were additionally controlled by Cutometer and Visioscan (Courage + Khazaka, Germany). The first signs in improving the texture and pigmentation of the skin became noticeable after the third radiation session. Similar results were observed when using as a source of light radiation the layout of the light device described in the above examples, in which a filter was installed to provide a spectral band from 500 nm to 2500 nm, in which it absorbs hemoglobin, melanin and water quite strongly. The duration of the pulses during the test irradiation was 1 s at a power density in the light spot of about 15 W / cm ² . The power density and pulse duration were reduced to 10 W / cm ² at 1 s and 15 W / cm ² at 0.7 s.

The desired effect in terms of the significance of difference from control was observed in the wavelength range from 500 nm to 2500 nm with values of power density from 80% up to 45% and pulse durations from 80% up to 10% of destructive values of power density and pulse duration, respectively.

Example 5. Reduction, including removal of sebaceous glands with acne

Sebaceous glands with acne are characterized by an increased size and increased secretion of sebum, leading to rupture of the hair follicle and inflammation. In accordance with the present invention, apoptosis of sebocytes and vascular cells of the sebaceous gland can be induced by non-damaging “soft” external light exposure, leading to a reduction in sebum secretion and remodeling of normal tissue. In contrast to the known methods of photocoagulation of the sebaceous glands with acne, in the present invention, the removal of vascular defects is atraumatic.

A diode laser with a wavelength of 920 nm was used as a source of light radiation, on which lipids — the main chromophores of the sebaceous glands of acne — absorb strongly enough.

Irradiation was performed on type II-III skin according to Fitzpatrick with acne on the back with a diameter of about 0.3 mm with an estimated thermal relaxation time of about 0.5 s. Immediately prior to irradiation, the skin was moisturized with water. Edema and erythema of the skin in the acne area immediately after the trial exposure served as a limiter to the power flow and pulse duration. The pulse duration in this test irradiation was 0.5 s with a power density in the light spot of about 80 W / cm ² .

The power density and pulse duration were reduced to 80 W / cm ² at 0.3 s and 60 W / cm ² at 1 s. The first signs of visual acne disappearance became noticeable 7 days after exposure.

Similar results were obtained using the layout of the lighting device described in the above examples, in which a filter was installed to provide a spectral band of 500-1800 nm absorption of hemoglobin / oxyhemoglobin and lipids. The power density and pulse duration were 30 W / cm ² , 20 W / cm ² and 1 s, 1.5 s, respectively.

The desired effect in terms of the significance of difference from control was observed in the wavelength range from 500 nm to 1800 nm with values of power density from 80% up to 45% and pulse durations from 80% up to 35% of destructive values of power density and pulse duration, respectively.

Example 6. Removal of neoplasms

The growth of neoplasms with sizes greater than 1-2 mm ^{3 is} accompanied by intense neovascularization along the periphery and within these neoplasms. The neoplasm vasculature provides its necessary nutrition and is mainly a chaotic interweaving of vessels with a density exceeding from several units to several tens of times the density of vessels in normal tissue. In accordance with the present invention, apoptosis of vascular cells of neoplasm vessels, such as warts, papillomas, carcinomas, psoriatic plaques, leading to thrombosis and atrophy of these vessels, followed by atrophy of the neoplasm itself and remodeling of normal tissue, can be induced by non-damaging “soft” external light exposure. In the case of pigmented neoplasms, absorption in melanin can be used. In contrast to the known methods of photodegradation, in the present invention, the removal of neoplasms occurs atraumatically.

Warts on the middle and index fingers of the right hand with type II skin according to Fitzpatrick were subjected to photoprocessing. Photo processing was carried out in several sessions with a time interval of 2-3 weeks.

The wart vasculature was considered either as a set of thermally unconnected single absorbing microvessels of the order of tens of microns in size with an estimated thermal relaxation time of about 1 ms, or as a single part of a biological tissue about 2-3 mm thick with an estimated thermal relaxation time of about 50-100 s. significantly exceeding the characteristic time of thermal diffusion from one vessel to another. In the latter case, the mechanism of apoptosis of neoplasm cells located between microvessels, leading to tissue remodeling as a whole, can be included. Accordingly, light sources were selected.

We used a KTP laser with a wavelength of 532 nm, which strongly absorbs blood hemoglobin - the main chromophore of the vascular system in this spectral range. Immediately prior to irradiation, the skin was moisturized with water. Edema and erythema of the skin immediately after trial exposure served as a limiter to the power flow and exposure duration. The power density in this test irradiation was about 2500 W / cm ² with a pulse duration of 2 ms.

The power density and pulse duration were reduced to 2000 W / cm ² at 2 ms and 2500 W / cm ² at 1.5 ms. The first signs of the visual disappearance of the warts became noticeable after the second radiation session.

Similar results were observed when using as a light source a prototype of the light device described in the above examples, in which a filter was installed to provide a spectral band from 500 nm to 1200 nm, in which it absorbs blood hemoglobin quite strongly. The duration of the pulses during the test irradiation was 20 s with a power density in the light spot of about 5 W / cm ² . The power density and pulse duration were reduced to 3 W / cm ² at 20 s and 5 W / cm ² at 12 s.

The desired effect in terms of the significance of difference from control was observed in the wavelength range from 500 nm to 1200 nm with values of power density from 80% up to 55% and pulse durations from 80% up to 65% of destructive values of power density and pulse duration, respectively.

Example 7. Reduction, including removal of hypertrophic and keloid scars

Developing hypertrophic and keloid scars are characterized by a red color, from pink to purple, due to nourishing capillary vasculature. In accordance with the present invention, through non-damaging “soft” external light exposure, apoptosis of vascular cell vessels of scar microvasculature can be induced, leading to thrombosis of these vessels with scar atrophy. In the case of hyperpigmented scars, absorption in melanin can be used. In contrast to the known photodegradation methods, in the present invention, the reduction of hypertrophic and keloid scars occurs atraumatically.

A hypertrophic postoperative scar 2 mm × 50 mm in size was placed on the arm with Fitzpatrick type II skin. Photoprocessing was carried out in several sessions with a time span of 4 weeks. A portion of the 5 mm long scar was used for test exposures.

Scar vasculature was considered either as a set of thermally unconnected single absorbing microvessels of the order of tens of microns in size with an estimated thermal relaxation time of about 1 ms, or as a single part of a biological tissue about 2 mm thick with an estimated thermal relaxation time of about 50-100 s, significantly exceeding characteristic time of thermal diffusion from one vessel to another. In the latter case, the mechanism of apoptosis of fibroblasts located between microvessels with subsequent remodeling of the tissue as a whole can also be included. Accordingly, light sources were selected.

We used a KTP laser with a wavelength of 532 nm, which strongly absorbs blood hemoglobin - the main chromophore of the vascular system in this spectral range. Immediately prior to irradiation, the skin was moisturized with water. Edema and erythema of the skin immediately after trial exposure served as a limiter to the power flow and exposure duration. The power density in this test irradiation was about 3000 W / cm ² with a pulse duration of 2 ms.

The power density and pulse duration were reduced to 2400 W / cm ² at 2 ms and 3000 W / cm ² at 1.5 ms. Scars, unlike the normal dermis, do not have increased echogenicity, apparently due to the disorder of collagen fibers. The first signs of visual scar reduction became noticeable after the third irradiation session.

Similar results were observed when using as a light source a prototype of the light device described in the above examples, in which a filter was installed to provide a spectral band from 500 nm to 1200 nm, in which it absorbs blood hemoglobin quite strongly. The duration of the pulses during the test irradiation was 20 s with a power density in the light spot of about 4 W / cm ² . The power density and pulse duration were reduced to 2.4 W / cm ² at 20 s and 4 W / cm ² at 12 s.

The desired effect in terms of the significance of differences from the control was observed in the wavelength range from 500 nm to 1200 nm with power densities from 85% up to 60% and pulse durations from 80% up to 70% of destructive values of power density and pulse durations, respectively.

It should be noted that during photo processing in areas irradiated with light radiation with an apoptotropic energy density, there were no cosmetically significant side effects and complications. At the same time, at an energy density destructive for chromophore-containing parts, in about 80% of irradiations, blisters and hyperpigmentation were observed due to competing absorption of part of the light radiation in the melanin-containing basal layer. This result indicates that the use of destructive values of the energy density inevitably leads to damage to the epidermis during percutaneous irradiation and in most cases requires special cooling systems.

Claims (22)

1. A method of photoprocessing a living biological tissue that causes apoptosis of cells of a portion of a biological tissue containing a chromophore that provides selective absorption of light radiation relative to the rest of the biological tissue, characterized in that this biological tissue is irradiated with light radiation with a wavelength of from 500 to 2500 nm with an energy density insufficient for destruction, but sufficient to induce apoptosis of cells of this part of the biological tissue. 2. The photo-processing method according to claim 1, wherein the biological tissue comprises skin and appendages. 3. The photo-processing method according to claim 1, wherein the instantaneous temperature of the chromophore-containing part of the biological tissue is from 43 to 135 ° C. 4. The photo-processing method according to claim 1, in which the energy density of light radiation is from 10 to 90% of the energy density that causes tissue destruction due to thermonecrosis. 5. The photo-processing method according to claim 1, in which this biological tissue is irradiated transversely. 6. The photo-processing method according to claim 5, wherein the instantaneous temperature of the surface of the biological tissue in the irradiation region is maintained close to physiologically normal due to heat removal during this irradiation. 7. The photoprocessing method according to claim 6, in which this biological tissue is irradiated through an optically transparent thin plate in optical contact with the surface of the biological tissue. 8. The photo-processing method according to claim 7, in which the plate is in thermal contact with the surface of the biological tissue and heat is removed through this plate to maintain the instantaneous temperature of this surface during irradiation close to physiologically normal. 9. The photo-processing method according to claim 1, in which the biological tissue is irradiated in a single-pulse exposure mode. 10. The photo-processing method according to claim 1, in which the biological tissue is irradiated in a multi-pulse exposure mode. 11. The photo-processing method according to claim 1, in which the biological tissue is irradiated repeatedly. 12. The photo-processing method according to claim 1, wherein the biological tissue is irradiated with coherent light radiation. 13. The photo-processing method according to claim 1, in which the biological tissue is irradiated with incoherent light radiation. 14. The photo-processing method according to claim 1, in which the biological tissue is irradiated with monochromatic light radiation. 15. The photo-processing method according to claim 1, in which the biological tissue is irradiated with broadband light radiation. 16. The method of skin photoprocessing, causing apoptosis of keratinocytes of the epithelium and vascular cells of the hair follicles, leading to growth inhibition, including removal of these follicles, characterized in that this skin is irradiated with light radiation with a wavelength of from 500 to 1200 nm with an energy density insufficient for destruction but sufficient to induce apoptosis of keratinocytes of the epithelium and vascular cells of these follicles. 17. The method of skin photoprocessing, causing apoptosis of vascular cells of vascular defects, leading to reduction, including removal of these defects, characterized in that this skin is irradiated with light radiation with a wavelength of from 500 to 1200 nm with an energy density insufficient for destruction, but sufficient to induce apoptosis of vascular cells of these defects. 18. The method of skin photoprocessing, causing apoptosis of keratinocytes and pigment spots melanocytes, leading to reduction, including the removal of these spots, characterized in that this skin is irradiated with light radiation with a wavelength of from 500 to 900 nm with an energy density insufficient for destruction, but sufficient to induce apoptosis of keratinocytes and melanocytes of these spots. 19. The method of skin photoprocessing, causing apoptosis of the epidermal basal keratinocytes and vascular cells of the upper dermis of the skin, leading to remodeling of this skin, characterized in that this skin is irradiated with light radiation with a wavelength of 500 to 2500 nm with an energy density insufficient for destruction, but sufficient to induce apoptosis of the basal keratinocytes of the epidermis and vascular cells of the upper dermis of this skin. 20. The method of skin photoprocessing, causing apoptosis of sebocytes and vascular cells of the sebaceous glands with acne, leading to the reduction of these glands, characterized in that this skin is irradiated with light radiation with a wavelength of 500 to 1800 nm with an energy density insufficient for destruction, but sufficient to induce apoptosis of sebocytes and vascular cells of these glands. 21. The method of skin photoprocessing, causing apoptosis of vascular cells of neoplasms, leading to the removal of these neoplasms, characterized in that this skin is irradiated with light radiation with a wavelength of 500 to 1200 nm with an energy density insufficient for destruction, but sufficient to induce apoptosis of vascular cells these neoplasms. 22. The method of skin photoprocessing, causing apoptosis of vascular cells of hypertrophic and keloid scars, leading to reduction, including removal of these scars, characterized in that this skin is irradiated with light radiation with a wavelength of from 500 to 1200 nm with an energy density insufficient for destruction, but sufficient to induce apoptosis of vascular cells of these scars.

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