RU2750975C1 - Method of photodynamic therapy with intradermal photosensitization - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to dermatology, gynecology, oncology, and can be used for photodynamic therapy with intradermal photosensitization of skin lesions and photoaging skin. For this, non-ablative photothermolysis of the affected area is carried out by scanning laser radiation in the range of 970-2000 nm with an average power of no more than 4 W in a pulsed mode with a frequency of 50 Hz, a pulse duration of 10 ms and a pulse energy of 0.0 6-0.1 J. Then, for no more than 3 hours, a photosensitizer, which is a derivative of chlorin E6, is applied to the skin, after which the excess of the photosensitizer is removed and the photosensitized area is irradiated with scanning laser radiation with a wavelength of 662 nm with an average power of 1-2 W in a pulse-periodic mode with a frequency of 5 Hz and pulse duration 100 ms. The course of treatment includes one or more procedures, depending on the degree of skin damage by the pathological process.

EFFECT: method allows to increase the efficiency of photodynamic therapy of age-related skin changes, benign, malignant, infectious-inflammatory, degenerative-dystrophic diseases of the skin due to the increased depth of intradermal transport of the photosensitizer through microthermal zones with a sparing nature of the photodynamic reactions induced in tissues and a reduction in the duration of the photosensitization process and the number of FF sessions.

5 cl, 1 tbl, 1 ex

Description

The invention relates to medicine, namely to methods for non-invasive treatment of skin diseases (malignant, dysplastic, dystrophic, infectious), as well as other diseases with a superficial manifestation. The invention can be used in oncology, gynecology, dermatology, cosmetology, as well as in aesthetic medicine for the purpose of skin rejuvenation.

In order to increase the efficiency and safety of aging skin correction, methods of laser rejuvenation and treatment of various skin defects have been developed, based on the absorption of laser radiation energy by skin chromophores.

Depending on the degree of laser thermal tissue damage, an ablative effect (invasive technique with mechanical tissue removal) and non-ablative laser irradiation (non-invasive technique without mechanical tissue destruction) are distinguished.

Ablative lasers (CO ₂ laser and Er: YAG laser) remain the gold standard for skin rejuvenation procedures, providing significant clinical improvement with a minimum of laser treatments. Ablative rejuvenation is accompanied by an increase in skin turgor, a decrease in superficial and deep wrinkles, and a decrease in dyschromia. However, due to significant trauma to the epidermis and dermis during ablation, the subsequent restoration of the skin is prolonged in time and is associated with the risk of complications. In addition, even superficial laser ablation of the skin carries the risk of subsequent hypopigmentation and post-burn scarring of the dermis.

Non-ablative fractional laser photothermolysis with the generation of short powerful pulses of laser radiation energy affecting the skin surface, breaking its protective barrier and creating a multitude of microscopic vertical coagulated channels of irradiated tissue with a depth of 0.1-0.2 mm, forming microthermal areas surrounded by an area of non-coagulated tissues.

For non-ablative skin remodeling procedures, lasers in the 970-2000 nm range are used. The radiation energy of such lasers has a greater penetration depth than ablative Er: YAG and CO ₂ lasers. Non-ablative lasers minimize the risk of complications by delivering laser light directly to the dermis and leaving the epidermis intact. In response to fractional laser photothermolysis, collagenogenesis is activated, resulting in skin rejuvenation. However, the absence of epidermal damage reduces the effectiveness of the procedure, which requires the implementation of a significant number of repeated exposures to achieve sustained clinical improvement [Rinaldi F. Laser: a review. ClinDermatol 2008 Nov-Dec; 26 (6): 590-601].

The disadvantages of this method are side effects, which are represented by transient erythema and peeling of the skin within 1 week, reversible edema, as well as episodes of exacerbation of herpes infection, requiring prophylactic antiviral therapy.

There is a method of photodynamic skin therapy (PDT), which provides for the healing and health effects of laser energy of a certain wavelength on the skin in the presence of photosensitizers [T.E. Sukhova, Yu.S. Romanko, O.V. Matveeva. Photodynamic therapy of basal cell skin cancer with local application of Radachlorin. Russian Journal of Skin and Venereal Diseases. - 2008. - No. 4. - С41-45].

The key factor is the ability of the photosensitizer to selectively accumulate in tumors and infectious agents, which makes it possible to use the photodynamic response to achieve healing effects.

Photodynamic therapy in cosmetology and dermatology is based on the initiation of controlled processes of photodestruction in the stratum corneum and epidermis, where the photosensitizer applied to the skin is absorbed by defective (hyperproliferative, malignant, inflamed) cells. The action of the photosensitizer is based on the formation of singlet oxygen in the presence of light energy, resulting in apoptosis and necrosis of photosensitized cells.

Photodynamic therapy is a non-invasive technique that eliminates thermal damage and post-procedural hyperpigmentation, but lacks the potential for deep dermal remodeling, which is characteristic of fractional laser photothermolysis.

The photodynamic method has disadvantages. In particular, the absorption coefficient of optical radiation by biological tissue in the red region is 10 ² cm ^-1 , therefore, it is possible to realize photodynamic effects in the depth of the dermis only with an increase in the power of the laser radiation energy, which will be accompanied by excessive photochemical burns and necrosis of the epidermis with tissue edema and pain syndrome. Another disadvantage of the PDT method is the repetitiveness of procedures at intervals of 2 weeks, adverse inflammatory effects in the form of erythema, exudation, and sometimes urticaria and other rare side effects such as scars, changes in hair growth and pigmentation, and allergic reactions.

The objective of our invention was to eliminate the above disadvantages by carrying out non-ablative fractional laser photothermolysis, supplemented by photodynamic therapy with cutaneous (surface) photosensitization.

Unlike traditional PDT methods with cutaneous photosensitization, we propose PDT after non-ablative laser photothermolysis and subsequent local surface photosensitization with preparations containing chlorin E6 (Radagel, Photoditazin-gel, "REVIXAN-DERMA"), which has not been previously used in this combination. With this procedure of laser skin treatment, many microthermal zones are formed in the stratum corneum, which creates conditions for the penetration of medicinal photosensitizers into the deeper layers of the skin. The use of repetitively pulsed non-ablative laser radiation minimizes the risk of complications, leaving the epidermis intact even without additional cooling of the skin surface.

The technical result of the proposed invention is to increase the efficiency of photodynamic therapy of age-related skin changes, benign, malignant, infectious-inflammatory, degenerative-dystrophic skin diseases due to the increased depth of intradermal transport of the photosensitizer through microthermal zones, as well as more effective irradiation of photosensitized skin structures with focused pulsed laser radiation with a high energy density (up to 200 J / cm ² ), and the gentle nature of the photodynamic reactions induced in tissues is provided due to the time of laser energy supply, which is shortened to 100 milliseconds.

Advantages of the method: the delivery of the photosensitizer to the affected areas of the skin is performed by a non-invasive application method; non-invasive fractional laser photothermolysis provides deep intradermal transport of the photosensitizer and significantly reduces the time of its penetration into the skin structure; photodynamic therapy with scanning pulsed laser radiation with an average power of 1-2 W, focused on the skin surface, does not require anesthesia, since the irradiation process is carried out in a pulse-periodic mode with a frequency of 5 Hz with a pulse duration of 100 ms.

Thus, the invention is a non-ablative fractional laser photothermolysis in combination with targeted application photosensitization of the epidermis and sub-epidermal layers of the skin and photodynamic therapy. Thanks to the new method, it becomes possible to increase the efficiency of the procedure, reduce post-procedural complications, reduce the duration of the photosensitization process and the number of PDT sessions.

The method is carried out as follows.

On the previously cleansed skin, non-ablative photothermolysis is performed with pulsed infrared laser radiation in the wavelength range of 970-2000 nm, with an average power of no more than 4 W. The pulse repetition rate is 50 Hz, the pulse duration is 10 ms. Irradiation is performed in scanning mode through a light guide with a focusing device, which forms a spot with a diameter of 0.5 mm on the tissue surface. When a pulse of laser energy of 0.06-0.1 J is applied through the focusing device to the tissue, microthermal zones are formed in the epidermis for intradermal penetration of the photosensitizer drug. The density of such zones should be at least 25 per 1 cm ² . Then a photosensitizer with chlorin E6 is applied to the skin, for example, Radagel 0.5% (from 0.5 to 1.0 g), and after 20-30 minutes the unabsorbed residue of the drug is removed from the skin surface. After that, the skin is irradiated in a scanning mode through an optical fiber with a focusing lens, creating a grid on the skin surface of points of light exposure with a density of not more than 100 points per 1 cm ² . Irradiation is carried out with the light energy of a semiconductor laser Lakhta-Milon, Latus, or Alod-01, generating repetitively pulsed radiation at a wavelength of 662 nm (in the spectral range of the maximum absorption of the photosensitizer) with an average power of 1-2 W. The pulse repetition rate is 5 Hz with a pulse duration of 100 ms.

The course includes one or several procedures, depending on the degree of skin lesion by the pathological process and in accordance with the clinical plan of treatment.

As evidence of the advantages of the developed technology, we present the result of a comparative experimental study on three groups of outbred mice aged from 3 to 5 months.

The experiment was carried out on the basis of the laboratory "Vivarium of conventional animals" ICG SB RAS. All 30 animals had their hair removed from the chest and abdominal walls.

The first, conditionally control group (n = 10) underwent the procedure of intravital non-invasive fractional laser photothermolysis of the skin with a semiconductor laser "Lakhta-Milon" (λ = 970 nm) with an average power of 4 W in a scanning pulse-periodic mode with a pulse duration of 10 ms at a frequency of 50 Hz (t = 10 ms, f = 50 Hz) through a quartz-polymer fiber with a focusing device for the formation of microthermal zones (MTZ) in the skin with a density of 30 MTZ / cm ² without subsequent photosensitization. Immediately after exposure to the skin, half of the individuals (n = 5) were withdrawn from the experiment to study the fluorescence of the skin layers by confocal microscopy.

The second study group (n = 10) underwent cutaneous application of the photosensitizer Radagel 0.5% -0.1 g for 20 min, after which non-absorbed drug residues were removed and half of the group (n = 5) was withdrawn from the experiment to study the fluorescence of skin layers using confocal microscopy. The remaining 5 individuals underwent intravital laser PDT of photosensitized skin with light energy of a wavelength of 662 nm and a power of 2 W in a scanning pulse-periodic mode with a laser pulse duration of 100 ms at a frequency of 5 Hz (t = 100 ms, f = 5 Hz) through an optical a fiber with a lens focusing on the skin a light spot with an area of 0.002 cm ² , providing a laser energy density on the tissue surface of 40 J / cm ² .

The third study group (n = 10) underwent non-invasive fractional photothermolysis of the skin with a semiconductor laser "Lakhta Milon" (λ = 970 nm) with an average power of 4 W in a scanning pulse-periodic mode (t = 10 ms, f = 50 Hz) through quartz polymer light guide with a focusing device for the formation of microthermal zones in the skin with a density of 30 MTZ / cm ² . Then the photosensitizer Radagel 0.5% - 0.1 g was applied to the skin, and after 20 minutes the rest of the preparation was removed from the skin surface. After that, five individuals (n = 5) were withdrawn from the experiment to assess the fluorescence of the skin layers by confocal microscopy. The remaining five animals underwent photodynamic therapy, in which the skin was irradiated with pulsed laser radiation with a wavelength of 662 nm and a pulse duration of 100 ms, operating at a frequency of 5 Hz (t = 100 ms, f = 5 Hz). Radiation at an average laser power of 2 W was applied in a scanning mode through an optical fiber with a lens forming a light spot on the skin with an area of 0.002 cm ² , which provided an energy supply of 0.4 J to one point per pulse at an average energy density created on the skin surface of 40 J / cm ² .

Animals of all groups, both withdrawn early from the experiment to study the fluorescence of skin layers by confocal microscopy, and left until the 7th day of observation, were euthanized by dislocation of the cervical vertebrae and the skin exposed to laser exposure was excised for subsequent pathohistological examination.

From the obtained skin samples, cryosections were prepared for examination on a laser scanning confocal microscope LSM 780 NLO AxioObserver Z1 (Zeiss, Germany) on the basis of the ICG SB RAS. The authors are grateful to the Center for Shared Use of Microscopic Analysis of Biological Objects SB RAS (http://www.bionet.nsc.ru/microscopy/) for the equipment provided. Microscopy was performed at optimal wavelengths for the study: excitation of fluorescence at 458 nm, registration of fluorescence at 675 nm. Image processing was performed using ZEN 2010 software. As a result of image analysis, graphs of the intensity of Radagel fluorescence in various layers of the skin were obtained, expressed in arbitrary units (a.u.), and based on the obtained values, conclusions were made about the degree of intradermal distribution of the photosensitizer.

Table 1 shows the obtained data of measurements of the intensity of Radagel fluorescence in the layers of the skin of the studied groups. From the data in the table, it follows that in individuals of the first (control) group subjected to non-invasive fractional photothermolysis and did not have a photosensitizer application, there is practically no fluorescence in the skin layers. In the second group of individuals, with cutaneous photosensitization by Radagel, its intense fluorescence was recorded exclusively in the epidermis and papillary layer, while in the third group, cutaneous photosensitization by Radagel, performed immediately after the procedure of non-ablative fractional laser photothermolysis, was accompanied by rapid and deep intra- and transdermal transport. photosensitizer, increasing the intensity of its fluorescence 5.5 times in the epidermis and papillary layer, 6.2 times in the reticular layer, and 1.6 times in the hypodermis.

The obtained results of experimental studies on animals in vivo convincingly prove the superiority of the proposed method of non-invasive fractional laser photothermolysis, which creates conditions for intradermal transport of a photosensitizer from the skin surface with the aim of the subsequent successful implementation of the therapeutic and photo-rejuvenating effects of PDT in deep layers of the skin previously inaccessible for treatment.

Confirmation of this position was obtained as a result of a comparative pathohistological study of skin samples, which established that in the second group on the 7th day after PDT, performed after application of photosensitization by Radagel, there is a significant thickening of the stratum corneum against the background of thinning of the prickly, granular and basal layers of the epidermis with depletion of cellular elements due to photodestruction. Thus, PDT is unable to rid the skin of excess keratinized epithelium, and a significant thickening of the papillary and reticular layers with impaired differentiation and a decrease in the volume of interstitial spaces indicates the consequences of photochemical burns with thinning of the epidermis.

In individuals of the third group, subjected to fractional photothermolysis of the skin with subsequent application of photosensitization of the skin and PDT procedure, on the 7th day after exposure, complete preservation of the cellular composition and differentiation of the epidermis, loosening of the papillary and pronounced structure of the compacted reticular layers of the dermis in the absence of traces of damage were recorded. The most significant criterion for successful photorejuvenation of the skin was also histologically confirmed, which manifested itself in an increase in staining of skin layers due to a significant increase in collagen production by activated fibroblasts.

As evidence of the advantages of the proposed PDT method, we present the following clinical example.

Clinical example

Patient D., 66 years old. I contacted Professor Pasman's Clinic LLC for the first time on 05/20/2017 with complaints of debilitating itching of the vulva. History: complaints of itching since 2014. When examined by a gynecologist, whitish plaques around the clitoris were revealed. According to the histological examination of the biopsy material of the skin of the vulva, vulvar leukoplakia was verified, which was removed by laser coagulation. After the healing of the coagulated surfaces, treatment with Ovestin was prescribed, however, the suffering did not alleviate, and the changes on the vulva persisted. Photodynamic therapy is recommended by the attending physician. The patient arrived for treatment on 05/20/2017. During a gynecological examination, typical changes in the vulvar integument, characteristic of leukoplakia, were recorded. Indications for PDT of leukoplakia with local photosensitization of the vulva and perineum were confirmed. 3 hours after application photosensitization with Radagel, the excess of the drug was removed from the skin with a damp cloth and the first PDT procedure was undertaken with monopositional radiation of a Latus Mask LED matrix emitter in the wavelength range of 650-675 nm at a luminous flux energy density of 70 J / cm ² . The duration of the procedure is 35 minutes. After treatment, the complaints disappeared completely within a few days, and a full night's sleep was restored. However, after three months, complaints began to recur, and during a gynecological examination, human papillomaviruses of 16 and 45 types were detected in the analysis of the scraping of the vulva by the PCR method. Against the background of continued treatment with Ovestin in combination with antiviral therapy, the elimination of viruses did not take place, and in the cytological study of the vulvar integument, the cytogram corresponded to hyperkeratosis.

04/27/2018 undertaken non-invasive photodynamic fractional photothermolysis of the vulva in accordance with the claimed method. 3 hours after the application of photosensitization of the vulva with Radagel 0.5% -1 g, its excess was removed with a damp cloth and photodynamic therapy was performed in a scanning pulse-periodic mode with a focused laser radiation of the Latus generator at a wavelength of 662 nm at a radiation power of 2 W, pulse duration of 100 ms at a frequency of 5 Hz. There were no complications. After the procedure, the patient's health improved and complaints of itching disappeared from 2 days. A control gynecological examination 1 year 6 months after the procedure (02.11.2019) revealed that all surfaces of the vulva regained an even pink tint and normal elasticity. The previously existing marginal lichen sclerotic on the outer edge of the left labia minora has completely disappeared, and in the areas of the former leukoplakia there is a healthy epidermis with a pinkish tint. There was a uniform brown pigmentation of the previously depigmented vulvar integument. On the basis of the absence of complaints and pathological manifestations of leukoplakia, a distinct local therapeutic and health-improving effect of treatment was recognized with the disappearance of all complaints. On the basis of the negative data of the PNR of human papillomaviruses of 16 and 45 types in the scrapings of the vulva, the antiviral effect of the performed procedure was proved.

In the presented example, the insufficient clinical efficacy of laser thermal destruction of vulvar leukoplakia and the standard single PDT procedure with application photosensitization by Radagel is obvious. The temporary relief achieved with the help of PDT turned out to be insufficient for the elimination of human papillomaviruses, which play a significant role in the pathogenesis of leukoplakia and other degenerative diseases of the vulva. After 11 months, a single procedure of photodynamic therapy of the vulva with the application of a photosensitizer at the same dose, but performed after non-invasive fractional photothermolysis, ensured the elimination of papillomavirus infection and the replacement of the pathologically altered vulvar covers with healthy epithelium with restored pigmentation.

ATTACHMENT 1

Examples of using the "Method of photodynamic therapy with intradermal photosensitization"

Example 1

Patient: A., 7 years old.

The girl is presented for examination by her mother.

Complaints: relapses of viral warts on the fingers of the left hand

Anamnesis: Over the past year, the parents have repeatedly introduced the girl to dermatologists about warts that have grown on the fingers of the left hand. For 4 months, the girl underwent six very painful cryodestruction procedures for viral warts of the left hand for therapeutic purposes. The treatment turned out to be so ineffective that all the warts recurred in the same places, and new elements have affected all the nail folds.

Status localis: On the dorsum of 2-3-4 fingers of the left hand in all phalanges there are multiple verrucous exophytic and flat elements with diameters from 2 to 3 mm.

Diagnosis: Vulgar viral warts 2-3-4 fingers of the left hand.

Progressive current. Condition after multiple cryodestruction of warts.

Conclusion: A 7-year-old child was diagnosed with a recurrent and progressive disease of the skin of the left hand with a total defeat of viral warts on the dorsal surfaces of all phalanges of 2-3-4 fingers.

The ineffectiveness of multiple cryodestruction of multiple viral warts requires a change in treatment tactics towards minimally invasive painless effective antiviral treatment in the volume of multi-course laser PDT.

05.10.2018. Manipulations: Non-ablative laser fractional photothermolysis of the affected surfaces of 2-3-4 fingers of the left hand, followed by application photosensitization with Radagel 0.5% - 0.5 g. After 3 hours, the excess photosensitizer was removed from the skin with a damp cloth.

Surface irradiation of the photosensitized skin of the fingers was performed in a scanning mode of pulsed laser radiation with a wavelength of 662 nm and a power of 2 W with a pulse frequency of 5 Hz. Laser energy was applied to the affected skin using a focusing light guide. There were no complications.

According to the treatment plan, the child underwent three painless
PDT procedures at two-week intervals.

3 months after the final PDT procedure, a control examination was performed to assess the achieved therapeutic effects. The fact of the absence of previously existing viral warts on the back surfaces of all phalanges of 2-3-4 fingers of the left hand was registered. A cure is diagnosed.

Example 2

Patient U., 46 years old. Throughout 2019, she repeatedly turned to cosmetologists and dermatologists with complaints of burning and discomfort from the integument of the lower lip and the growth of white dense plaque on the red border. Leukoplakia of the lower lip was pathohistologically verified. The patient was recommended photodynamic therapy. For this treatment, the patient was hospitalized in one of the medical institutions in Novosibirsk, where on December 24, 2019, she received an intravenous injection of the photosensitizer Radachlorin 0.35% - 20 ml, and after 3 hours PDT of leukoplakia of the red border of the lower lip was performed. The procedure caused a severe photochemical burn of the lower lip, swelling of the face, and prolonged suffering from pain caused by the burn of the lip. However, a month after the treatment, the patient noted a further deterioration in the condition of the lower lip, which was covered with a continuous dense coating of white color.

Realizing the fact of recurrence of the disease and the ineffectiveness of the treatment, the patient turned to us.

When examining the patient's lower lip, there is a total defeat of the entire area of the red border of the lower lip with a white dry dense bloom of leukoplakia, covered with rough scales. In the clinic, the patient was prescribed a multi-course treatment consisting of non-ablative fractional photothermolysis of the affected integument of the lower lip, application photosensitization with Radagel 0.5% and laser PDT in a pulsed mode through a light guide with a focusing device.

The first procedure was performed on March 21, 2020.The treatment protocol provided for non-ablative fractional photothermolysis of the red border of the lower lip using the radiation of a semiconductor laser Lakhta Milon at a wavelength of 970 nm with a power of 4 W in a pulsed mode of 50 Hz and with the supply of laser energy through a fiber with a focusing device, followed by an application photosensitization of the red border of the lower lip by Radagel 0.5% - 0.5 g with an exposure of 2 hours. Photodynamic therapy was performed in a scanning mode with a focused pulse energy of a Latus laser at a wavelength of 662 nm at a power of 1 W and a frequency of 5 Hz with a pulse duration of 0.1 sec supplied through a fiber with a focusing device. The effects of photodynamic therapy were felt by the patient as a slight tingling in the area of light exposure.

During the medical examination on 06/05/2020, when assessing the local status, it was noted that the pink border of the lower lip lost its pathological whitish striation and roughness, acquired a natural color. In the corners of the mouth there are barely noticeable residual whitish filamentous strips of leukoplakia 2 and 3 mm long. In the dynamics, an undoubted improvement is recorded under the influence of treatment. The patient received the second PDT procedure and, taking into account the therapeutic and health-improving effect, she was prescribed the third procedure for the complete cure of leukoplakia.

The third procedure, performed on July 24, 2020 in accordance with the approved protocol, was also free of complications and was not accompanied by pain and burn reactions.

4 months after treatment, at a control examination on November 24, 20, a complete clinical effect was registered, expressed by the absence of pathology on the red border of the lower lip. The lip surface has a healthy pink tint, elastic smooth epithelium without signs of leukoplakia. The patient expresses complete satisfaction with the therapeutic effect,
achieved through painless procedures free of complications.

Example 3

Patient K., 86 years old.

I applied on 10.08.2019 with complaints of a non-healing sore on the skin of the nasal dorsum. The disease developed for 5 months, from the spring of 2019, when a flaky crust appeared on the back of the nose, under which a non-healing sore formed. During cytological examination of the scraping of the ulcer, the basal cell carcinoma was verified.

The patient refused the proposed surgical treatment of basal cell carcinoma due to possible cosmetic damage and high surgical and anesthetic risk due to several concomitant diseases: arterial hypertension of the 2nd stage, ischemic heart disease, bilateral gonarthritis, osteochondrosis of the spine in the acute stage. As an alternative treatment, the patient chose an outpatient photodynamic therapy that does not require anesthesia.

In the clinic on August 27, 19, the patient underwent the procedure of non-ablative laser fractional photothermolysis of the skin of the nose using the radiation of a semiconductor laser Lakhta Milon at a wavelength of 970 nm with a power of 4 W in a pulsed mode of 50 Hz and with the supply of laser energy through a fiber with a focusing device. Immediately after photothermolysis, application photosensitization with a gel penetrator Photoditazin 0.5% -0.5 ml was performed (Registration certificate: No. FSR 2012/13043 dated June 08, 2017). After 3 hours, the applied gel was removed with a damp cloth and photodynamic therapy was performed in a scanning pulse-periodic mode with focused laser radiation of the Lakhta Milon generator at a wavelength of 662 nm at a radiation power of 2 W, a pulse duration of 100 ms at a frequency of 5 Hz. There were no complications. In the next three days after the procedure, the treated ulcer defect was transformed into a dense black crust, and after 2 weeks, this photonecrotic scab was spontaneously rejected, and during a medical examination, complete epithelialization of the ulcer defect with full clinical effect was established. Clinical well-being is documented one year after cure.

Example 4

Patient B., 52 years old.

I applied on 05/15/2020 with complaints of itching and redness of the skin of the chin and cheeks, the appearance of small pustules on the chin, loss of elasticity of the facial skin with sagging cheeks, deepening of nasolabial folds and small wrinkles at the outer corners of the eyes, the appearance of bags under the eyes. Professional history. Works as a dermatologist. Medical history. The appearance of these complaints is associated with a change in working conditions during the COVID-19 pandemic and the need to comply with the social distance regime, the constant wearing of protective masks, the regular use of skin antiseptics, and frequent washing with soap. The resulting changes in the skin of the face did not lend themselves to correction with the applied moisturizing and nourishing creams. The use of medical cosmetics in the form of external agents with retinol and preparations based on hyaluronic acid also did not have a significant healing effect. Allergic anamnesis is not burdened.

According to an objective examination, the patient is of the correct physique, moderate nutrition. Phototype II. The skin is clean.

Status localis. The skin of the cheeks and chin is hyperemic, dry to the touch, with reduced turgor, elasticity and volume. The contours of the face are changed by the developing ptosis of the cheeks. The nasolabial folds are deepened. At the outer corners of the eyes, small wrinkles in the form of "crow's feet" are formed. On the chin there are small dry crusts from the existing pustular eruptions.

Diagnosis: (L 57) photoaging. (L 57.4) Chrono aging. Chronic contact dermatitis.

Inspection report. Clinical manifestations of photo- and chrono-aging of the face in conditions of chronicity of contact "mask" dermatitis determine the choice of treatment tactics in favor of simultaneous correction of involutional skin changes and anti-inflammatory treatment using photodynamic therapy.

In accordance with the clinical design, the treatment protocol is composed of two procedures at two-week intervals. In the clinic on May 15, 2020, the patient underwent a procedure of non-ablative laser fractional photothermolysis of the skin of the face by radiation of a semiconductor laser IRE-Polyus at a wavelength of 1060 nm with a power of 4 W in a pulsed mode of 50 Hz and with the supply of laser energy to the skin through a fiber with a focusing device. After photothermolysis, application photosensitization was performed with the preparation Photoditazin 0.5% - 1 g in the form of a gel, after 30 minutes the excess of the gel was removed with a damp cloth. Photodynamic therapy was carried out in a scanning pulse-periodic mode with focused laser radiation of the Lakhta-Milon generator at a wavelength of 662 nm at a radiation power of 1 W, a pulse duration of 100 ms, and a pulse frequency of 5 Hz. There were no complications.

The second similar procedure was performed on 05/30/2020.

The assessment of therapeutic and health-improving effects and photorejuvenation was assessed once a week for 1 month after the first procedure.

During the first week after the 1st procedure, a number of favorable anti-inflammatory therapeutic effects were registered, represented by the disappearance of itching and hyperemia of the cheeks and chin, the resorption and disappearance of inflammatory elements on the chin, and the alignment of the complexion. Photorejuvenation was characterized by an increase in facial skin turgor, a decrease in the severity of fine wrinkles and a mesh at the corners of the eyes, smoothing of nasolabial folds and lightening of skin tone.

According to the GAIS (Global Aesthetic Improvement Scale), an objective assessment of the PDT effectiveness two weeks after the first procedure by the attending physician was 1 point (A noticeable improvement in appearance compared to the baseline), while the patient's subjective assessment was 2 points, which already corresponded to a moderately pronounced improvement.

A week after the second procedure, the skin looked practically healthy, and the effects of photorejuvenation were supplemented by the normalization of moisture and elasticity of the skin with further smoothing of nasolabial folds, reduction of ptosis of the skin of the lower eyelids and lifting of ptosis of the cheeks.

2 weeks after the second PDT procedure, due to the improvement of the face oval, the doctor's objective assessment and the patient's subjective assessment increased to 3 points, which corresponds to the criterion of significant improvement.

Claims (5)

1. A method of photodynamic therapy with intradermal photosensitization of lesions of the skin and photoaging skin, consisting in the fact that non-ablative photothermolysis of the affected area is carried out by scanning laser radiation, which creates microthermal zones on the skin surface, in the range 970-2000 nm with an average power of no more than 4 W in in a pulsed mode with a frequency of 50 Hz, a pulse duration of 10 ms and a pulse energy of 0.0 6-0.1 J, then a photosensitizer, which is a derivative of chlorin E6, is applied to the skin for no more than 3 hours, after which the excess photosensitizer is removed, then produced irradiation of a photosensitized area with scanning laser radiation with a wavelength of 662 nm with an average power of 1-2 W in a pulse-periodic mode with a frequency of 5 Hz and a pulse duration of 100 ms, the course of treatment includes one or more procedures depending on the degree of skin lesion by the pathological process. 2. The method according to claim 1, characterized in that the density of the created microthermal zones is at least 25 such zones per 1 cm ² . 3. The method according to claim 1, characterized in that Radagel 0.5% is used as a photosensitizer derived from chlorin E6. 4. The method according to claim 1, characterized in that the irradiation of the photosensitized skin area is performed with laser radiation in a scanning mode, creating a grid of light points on the skin surface with a density of not more than 100 points per 1 cm ² . 5. A method according to claim 4, characterized in that at the point of exposure to light, the area of the light spot is 0.002 cm ² at an energy density at the point of exposure of up to 200 J / cm ² .