RU2411049C1 - Method of treating patients with psoriasis - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention is referred to medicine, dermatology, and can be used for treating patients with psoriasis. That is ensured by a complex pathogenetic therapy followed by a photodynamic therapy. As a photosensitiser, the preparation photosense in ointment form is used. Photosense is applied on psoriatic skin rashes at concentration of an active substance 0.001-0.01 g/cm². Duration of an application is 1-12 hours. It is followed with local light radiation of pathological nidi at wave length 675 nm and power density 40 mWt/cm².

EFFECT: method allows to provide effective, low-toxic psoriasis treatment with prolonged remission, ensured complete clinical remission with minimum by-effects.

3 cl, 6 ex

Description

The invention relates to medicine, to the section of dermatology, and in particular to methods of treating patients with psoriasis.

Psoriasis is one of the most common pathologies in dermatological practice. This disease is genetically determined, and the provoking factors most often become a viral bacterial or mycotic infection, insolation, hypothermia, diseases of the internal organs, endocrinopathy, etc. Psoriasis is a systemic disease. A thorough examination of the patient using instrumental examination methods reveals, in addition to pathological changes in the skin, pathological changes in the parenchyma of the liver, kidneys, heart, pancreas, joints. Psoriasis is often accompanied by changes in blood serum, including: hypercholesterolemia, a decrease in total protein, hypergammaglobulinemia, an increase in direct and total bilirubin, ACT, ALT, creatinine, and lipids, which, in turn, can lead to a combination of various biochemical reactions to an increase in pathological symptoms, and secondarily signal the development of a systemic process.

In the treatment of this disease, various drugs (drugs) are used (detoxification, hormonal, cytostatics, etc.), physiotherapeutic techniques, and some alternative medicine methods.

Most drugs used have a number of side effects, which are often harder than the disease itself - all this forces dermatologists around the world to develop new methods of treatment. In recent years, photodynamic therapy (the use of photosensitizers and laser or diode radiation) has become increasingly popular.

A known method of treating psoriasis (A.Z. Kameneva "Selective phototherapy in the treatment of patients with psoriasis" is a dissertation abstract for the degree of candidate of medical sciences, Stavropol, 1998), including the influence of ultraviolet radiation with a wavelength of 311 nm, power density 200 mW / cm ² , the course of treatment included 10-43 procedures.

The disadvantages of the method include the high likelihood of burns and dermatitis, hyperpigmentation, a high dose of radiation to achieve a clinical effect, decreased efficiency during repeated courses of treatment, and the risk of potentiation of skin cancer. According to long-term results of the study, after repeated courses of treatment, the period of remission of this disease is reduced, which is an extremely unfavorable complication of this treatment method.

As the closest analogue (prototype), a method of treating patients with psoriasis (patent RU No. 2336917 A61N 5/06, 10/27/2008), which includes complex pathogenetic therapy with the use of hyposensitizing, antihistamines, detoxifying agents, hepatoprotectors, vitamin preparations, keratolytic and regenerating, has been adopted ointments, followed by photodynamic therapy with the drug "Photostim" related to chlorine photosensitizers and containing the active substance radachlorin E-6. The drug is administered orally in the form of a syrup. The introduction begins on the 3rd day from the beginning of treatment on an empty stomach in a dose of 5 ml daily for 30 days. Exposure to light radiation with a wavelength of 650 nm and a radiation power density of 50 mW / cm ^{2 is} carried out from the 7th day until the end of the Photostim reception.

However, the known method has several disadvantages. Chlorine photosensitizers are distinguished by poorly controlled distribution in the human body, which leads to the predominant accumulation of the drug in organs and tissues characterized by rapid cell division (psoriatic plaques, liver, kidneys, spleen, bone marrow). Accumulating these organs and tissues in the vessels of the microvasculature, Photostim, upon activation of the photodynamic reaction and the release of reactive oxygen species, can disrupt the integrity of the vascular walls, leading to disruption of microcirculation not only in pathological foci, but also in the liver, kidneys, spleen, bone marrow and some other organs and tissues, which further exacerbates the course of the psoriatic process. When analyzing the long-term results of treating patients with PDT with the Photostim preparation, an increase in liver enzyme levels, episodes of nephrotoxicity, allergic and phototoxic reactions were noted, which are unfavorable complications in multi-course treatment with a frequency of 2 or more times a year. Photostim can be taken no more than 30 days, and immunological restructuring in the human body is completed 2 months after the drug is discontinued, which in most cases does not allow for complete clinical remission, to predict the duration of the remission period, and to provoke various autoimmune reactions.

The objective of the invention was the creation of a more effective, low-toxic method of treating patients with psoriasis, to achieve complete clinical remission with a minimum of side effects.

The essence of the invention lies in the fact that the method of treating patients with psoriasis includes complex pathogenetic therapy with the use of hypersensitizing, antihistamines, detoxification drugs, hepatoprotectors, vitamin preparations and the subsequent PDT with photosensitizer "Photosens" in the form of an ointment for application that is applied to the affected areas of the skin cover upon reaching the stationary stage daily 5 times a week at a dose of 0.001-0.01 g / cm ² , the concentration of "Photosense" in the ointment is 0.1-1%, the duration of the application is 1-12 hours, followed by light exposure with a wavelength of 675 nm and a power density of 40 mW / cm ² . The dose of "Photosens" 0.001 g / cm ² is the minimum effective dose, and with a dose of more than 0.01 g / cm ² there is no clinically significant increase in the effectiveness of treatment, but the likelihood of phototoxic reactions increases; 1 h - the minimum exposure time of the ointment necessary to obtain a result; at an exposure of more than 12 hours, the photosensation oxidation will increase; the maximum absorption of light energy by Photosens occurs at a wavelength of 675 nm; 40 mW / cm ² is the generally accepted maximum power density value used to treat chronic dermatological diseases.

Using the invention allows to obtain the following technical result.

The method is effective for patients with a PASI index of up to 25, which is expressed in the rapid regression of rashes (up to 40 days on average), a long period of remission (up to 1 year on average).

Application application of the drug eliminates phototoxic damage to eye tissues and almost completely eliminates phototoxic skin reactions and the systemic toxic effect of Photosens on the liver and kidneys.

The method allows to achieve a complete regression of rashes within 40 days, reduce itching after the first exposure to light and stop it within 10 days from the start of treatment, significantly reduce infiltration, edema and erythema in patients with psoriasis after the first procedure of photodynamic therapy.

It helps to improve the quality of life of patients with psoriasis as a result of the rapid disappearance of itching, rapid and complete regression of rashes.

The method is low toxic. No allergic or toxic reactions were noted with the use of the drug.

The technical result is achieved due to the fact that "Fotosens" is a representative of the class of photosensitizers of the phthalocyanine series and represents the sodium salts of di-, tri- and tetrasulfosubstituted phthalocyanines of hydroxyaluminium (Russian Chemical Journal, 42 (5) p. 9-16, 1998) .

When applied to the affected areas of the human skin, this substance accumulates in several upper layers of the plaque and during the application period of 1-12 hours does not penetrate into the vascular bed, which causes its exceptional local effect. The mechanism of development of the psoriatic process is dominated by a violation of keratinization in certain areas of the skin, which leads to the formation of plaques consisting of keratinocytes in which apoptosis mechanisms do not work, in particular, the half-life of the P53 protein is reduced. Without light exposure, this substance is intact, but it absorbs visible light with a wavelength of 675 nm. When exposed to the specified light wavelength, the substance undergoes transformation with the formation of singlet oxygen, which damages the cell membrane, thereby leading to its death. In addition to the direct damaging effect on the cell, "Photosens" has an immunocorrective effect, which is proved in laboratory studies. After exposure to the drug, the level of TNF-alpha, IL-6 decreases, the half-life of the P53 protein increases, and the amount of Tx-1 decreases. These changes are stored for a long time. In all patients who do not abuse alcohol, remission after treatment persisted for more than a year.

Thus, the mechanism of action of the drug provides high treatment efficiency, low toxicity, lengthening the period of remission and activation of apoptosis mechanisms locally in altered cells, achieved by local light exposure, which leads to a clinical effect without damaging healthy cells.

The method is as follows.

Patients diagnosed with psoriasis are given complex therapy, including detoxification, hypersensitizing, antihistamines, vitamin preparations, hepatoprotectors, keratolytic and regenerating ointments, and upon reaching the stationary stage, they will undergo a course of photodynamic therapy with the Photosens drug in the form of an ointment. The procedures are carried out daily for 5 days followed by a 2-day break. The ointment includes a 0.2% Photosens solution and an ointment base (for example, a micellar-regenerating complex). The concentration of "Photosense" in the ointment is 0.1-1%, the dose of the active substance is 0.001-0.01 g / cm ² , and the required amount of ointment base is determined from the calculation of 0.5-1 g / cm ² . The duration of application of the ointment is 1-12 hours. After application, local light exposure is carried out. Use a red spectrum LED lamp. The wavelength is 675 nm, and the radiation power density is 40 mW / cm ² . The coverage area of the lamp is 5 cm ² , the effective exposure time to 5 cm ^{2 the} area of the pathological focus is 5-15 minutes. The number of procedures per course of treatment is 5-47.

Example 1. Patient S., 42 years old, suffers from a common form of psoriasis for 12 years. Rashes are localized on the skin of the elbows and the front surface of the legs. They are represented by coarse-grained elements with silver scales on the surface, peeling does not go beyond the pathological focus. The psoriatic triad is positive. Over the past 11 years, he repeatedly received treatment in a hospital, but clinical remission was not achieved. The last rashes appeared on June 13, 2008. The patient was given detoxification (sodium thiosulfate 10.0 10% No. 10 i / m every other day), hypersensitizing (calcium gluconate 10.0 30% No. 10 i / v every other day), antihistamine (suprastin i / m 1, 0 at night No. 10, erius 1 tablet per day No. 10), vitamin therapy (B1 and B6 1.0 v / m every other day No. 10) therapy, hepatoprotectors were prescribed (Karsil 1 tablet per day No. 30), local treatment was carried out with Advantan cream , upon reaching the stationary stage, the patient used a keratolytic cream with 10% BATRIUM urea at night.

Upon reaching the stationary stage (the absence of new rashes, a decrease in the level of erythema (redness) of the skin, a decrease in the intensity of peeling on the surface of the plaques), a photodynamic therapy was carried out with the Photosens drug in the form of an ointment that included a 0.2% solution of the Photosens drug and a micellar-regenerating complex.

The procedures were carried out five days daily, followed by a two-day break. The dose of the active substance was 0.005 g / cm ² , the concentration of the active substance in the ointment was 0.25%, the power density of the LED light source was 40 mW / cm ² , the duration of the exposure to 5 cm ² was 5 minutes.

Five photodynamic treatment procedures were performed. The patient was discharged with residual effects of infiltration, which regressed 14 days after discontinuation of treatment. During aftercare, keratolytic, moisturizing and regenerating ointments were used. During the course of photodynamic therapy procedures, no side effects or allergic reactions were noted. No remission was observed before the course of the photodynamic therapy procedures; after the PDT course, the remission was 6 months.

Example 2. Patient Z., 80 years old, was hospitalized with a newly diagnosed exacerbation of psoriasis. The identified form is common and exudative. Rashes are localized on the skin of the abdomen, lower back, front surface of the legs. They are represented by coarse-grained elements and a small-papular rash with silver scales on the surface, peeling does not go beyond the boundaries of the pathological focus. The psoriatic triad is positive. Detoxification therapy was carried out (sodium thiosulfate 10.0 10% I / O every other day, hemodesis 400.0 I / O drip No. 3), hypersensitizing (calcium gluconate 10.0 30% No. 10 I / O every other day), antihistamine (suprastin 1.0 I / m at night No. 10 daily, diazolin 1 tablet per day in the morning No. 10) therapy, vitamin therapy (B1, B6 1.0 v / m every other day No. 10), hepatoprotectors (Essentiale Fort 1 tablet 3 times a day No. 30 were prescribed) ), ATP at 1.0 v / m once a day No. 10, ointment therapy consisted in the use of Dexamethasone cream 2 times a day, upon reaching the stationary herds and used the BATRIUM keratolytic cream for the night. Upon reaching the stationary stage, photodynamic therapy was carried out with the Photosens preparation in the form of an ointment containing a 0.2% solution of the Photosens preparation and a micellar-regenerating complex.

The dose of the substance was 0.001 g / cm ² , the concentration of the substance in the ointment was 0.2%, the radiation power density was 40 mW / cm ² , the duration of the exposure to 5 cm ² was 5 minutes. Concomitant ointment therapy included a urea cream and a moisturizer. The course of treatment was 15 procedures. The patient was discharged in a state of clinical remission. Residual effects of infiltration and hyperpigmentation persisted. Exfoliating, moisturizing and regenerating agents were used. Rashes completely regressed. No adverse or allergic reactions were noted during treatment. The remission period was 1 year.

Example 3. Patient C., 25 years old, suffers from a localized form of psoriasis for more than 3 years. With exacerbation, he sought medical help. Rashes are represented by two large plaque elements on the anterior surface of the legs, covered with silver scales, peeling does not extend beyond the borders of the focus, the psoriatic triad is positive. Hyposensitizing (calcium gluconate, 1 tablet 3 times a day for 10 days), antihistamine (erius 1 tablet per day for 10 days, Xysal 1 tablet per day for 10 days), detoxification (hemodesis at 400.0 IV drip No. 3 through day) therapy, vitamin therapy (B1 to 1.0 every other day IM 10), hepatoprotectors (Essentiale Forte 1 tablet 3 times a day No. 30) were prescribed, Advantan cream was applied for local therapy, which was applied 2 times a day to plaques . Upon reaching the stationary stage, photodynamic therapy was carried out with the Photosens preparation in the form of an ointment containing a 0.2% solution of the Photosens preparation and a micellar-regenerating complex.

The dose of "Photosense" was 0.01 g / cm ² , the concentration of "Photosense" in the ointment was 1%, the power density was 40 mW / cm ² , the duration of light exposure to 5 cm ² was 15 minutes. Concomitant ointment therapy included a urea cream and a moisturizer. 47 procedures were performed. Rashes regressed, residual effects of infiltration and hyperpigmentation persisted. During aftercare, exfoliating, moisturizing and regenerating agents were used. 14 days after completion of the course of photodynamic therapy with the drug "Photosens" infiltration regressed, hyperpigmentation decreased. The remission period was 11 months, which is 1.5 months more than the average disease remission period for the entire period, starting from the first exacerbation. Adverse or allergic reactions are not marked.

Example 4. Patient L., 37 years old, suffers from psoriasis for more than 15 years. Rashes are located on the skin of the elbows, legs, scalp, back of the hands, represented by plaques of bluish-red color with silver scales on the surface, peeling does not extend beyond the borders of the focus, the psoriatic triad is positive. Detoxification therapy was carried out (sodium thiosulfate 10.0 10% No. 10 i / m every other day, hemodesis 400.0 i / v drip No. 5), hypersensitizing (calcium gluconate 10.0 30% No. 10 i / v every other day), antihistamine (suprastin 1.0 i / m at night No. 10 daily, erius 1 tablet per day in the morning No. 10) therapy, vitamin therapy (B6, 1.0 v / m every other day No. 10), hepatoprotectors were prescribed (Karsil 1 tablet per day No. 30), ATP 1.0 / m once a day No. 10, ointment therapy consisted in the use of Sinaflan cream 2 times a day on the affected areas of the skin, upon reaching the stats -stationary phase used keratolytic cream BATRIUM with urea at night. Upon reaching the stationary stage, photodynamic therapy was carried out with the Photosens preparation in the form of an ointment containing a 0.2% solution of the Photosens preparation and a micellar-regenerating complex.

The dose of the substance was 0.005 g / cm ² , the concentration of the substance in the ointment was 0.25%, the radiation power density was 40 mW / cm ² , the duration of the exposure to 5 cm ² was 5 minutes. Concomitant ointment therapy included a urea cream and a moisturizer. The course of treatment was 25 procedures. The patient was discharged in a state of clinical remission. Residual effects of infiltration and hyperpigmentation persisted. Exfoliating, moisturizing and regenerating agents were used. Rashes completely regressed. No adverse or allergic reactions were noted during treatment. The duration of the period of remission after treatment with PDT is 13 months. The median remission period before PDT treatment was 11 months.

Example 5. Patient D., suffers from a localized form of psoriasis for more than 12 years. With exacerbation, she sought medical help. Rashes were localized on the skin of the anterior surface of both legs, represented by plaques of bluish-red color with silver scales on the surface, peeling does not extend beyond the borders of the focus, the psoriatic triad is positive.

Detoxification therapy (sodium thiosulfate 10.0 10% No. 10 iv every other day), hyposensitization (calcium gluconate 10.0 30% No. 10 iv every other day), antihistamine (erius 1 tablet per day in the morning No. 10), vitamin therapy were performed. (B1 and B6, 1.0 v / m every other day No. 10), hepatoprotectors (Essential Forte 1 tablet 3 times a day No. 90) were prescribed, ointment therapy was carried out with Advantan cream twice a day to the affected areas of the skin. Upon reaching the stationary stage, photodynamic therapy is attached with the Photosens drug in the form of an ointment, including a 0.2% solution of the Photosens drug and a micellar-regenerating complex.

The dose of the substance was 0.001 g / cm ² , the concentration of the substance in the ointment was 0.2%, the radiation power density was 40 mW / cm ² , the duration of the exposure to 5 cm ² was 5 minutes. Concomitant ointment therapy included a urea cream and a moisturizer. The course of treatment amounted to 17 procedures. The patient was discharged in a state of clinical remission. Residual effects of infiltration and hyperpigmentation persisted. Exfoliating, moisturizing and regenerating agents were used. Rashes completely regressed. No adverse or allergic reactions were noted during treatment. The duration of the remission period was 11 months. The average period of remission before treatment with photodynamic therapy was 5.5 months.

Example 6. Patient I., suffers from a common form of psoriasis with exudative manifestations for more than 30 years. Six years ago, he suffered an ischemic stroke, paresis of the left half of the body was noted, in the process of rehabilitation, motor activity was partially restored. The patient is hospitalized. Rashes are located on the skin of the forearms and the front surface of both legs. They are represented by coarse plaque elements of bluish-red color with pronounced infiltration and exudation, the process is more pronounced on the left arm and leg.

Detoxification was carried out (sodium thiosulfate 10.0 10% No. 10 i / m every other day), hypersensitizing (calcium gluconate 10.0 30% No. 10 i / v every other day), antihistamine (suprastin i / m 1.0 at night No. 10 , Erius 1 tablet per day No. 10) therapy, vitamin therapy (B1 1.0 v / m every other day No. 10), hepatoprotectors were prescribed (Karsil 1 tablet per day No. 30), ATP 1 was prescribed to improve tissue nutrition, 0 v / m in a day No. 10, preparations for the correction of neurological and cardiological disorders, local treatment was carried out with Lorinden A cream (applied 2 times a day for 1 4 days).

The stationary stage was reached a month later. Photodynamic therapy was carried out with the Photosens drug in the form of an ointment, including a 0.2% solution of the Photosens drug and a micellar-regenerating complex, after agreement with the therapist, cardiologist and neuropathologist.

The dose of the substance was 0.005 g / cm ² , the concentration of the substance in the ointment was 0.25%, the radiation power density was 40 mW / cm ² , the duration of the exposure to 5 cm ² was 5 minutes. Concomitant ointment therapy included a urea cream and a moisturizer. The course of treatment was 30 procedures. The patient was discharged in a state of clinical remission.

Residual effects of infiltration and hyperpigmentation persisted. Exfoliating, moisturizing and regenerating creams are used. The average duration of the period of remission before treatment with PDT with the Photosens drug was 9 months; after treatment, remission was 11.5 months.

The proposed method for treating psoriasis patients with PDT using the Photosens drug as an ointment was tested on 85 patients (40 women and 45 men) (volunteers). The study included patients with local (70) and common (15) forms of psoriasis. The large plaque form prevailed. The study did not include patients with complicated forms of psoriasis - arthropathy and erythroderma. Complete remission was achieved in 72% (61) cases, partial remission in 17% (15), therapy was ineffective in 11% (9) patients, the lack of treatment effect in 9 patients, according to the authors, is associated with severe concomitant somatic pathologies , alcoholism and high activity of the enzyme superoxide dismutase. No allergic or toxic reactions have been observed. Remission in 95% of cases was more than 1 year; in 5%, exacerbation began after drinking.

Thus, an effective, low-toxic method of treating psoriasis has been proposed, which allows to lengthen the period of remission, to achieve complete clinical remission with a minimum of side effects.

Claims (3)

1. A method for the treatment of psoriasis patients, including complex pathogenetic therapy and subsequent photodynamic therapy, characterized in that the photosensitizer uses the drug "Photosense" in the form of an ointment, which is applied on psoriatic rashes with an active substance concentration of 0.001-0.01 g / cm ² , the application duration is 1-12 hours, then local light irradiation of pathological lesions with a wavelength of 675 nm and a power density of 40 mW / cm ^{2 is} carried out. 2. The method according to claim 1, characterized in that the concentration of "Photosense" in the ointment is 0.1-1 wt.%. 3. The method according to claim 1, characterized in that the course of treatment is from 5-47 photodynamic therapy procedures.