RU2107910C1 - Method for treating cardiac ischemia disease - Google Patents

Abstract

FIELD: medicine. SUBSTANCE: method involves additionally administering aspirin and Aevit in addition to combined helium-neon laser therapy and medical drug treatment, daily during the whole treatment course. Antithrombin III value (AT III) and the level of general antioxidation activity in blood are controlled (before and after helium-neon laser therapy). The value of AT III being lowered with respect to norm, helium-neon laser therapy is applied each second-third day and every day in other cases. Maximum values of antioxidation activity being stabilized, intravenous injections are finished and skin procedures are started. The procedures are applied every day or every second day during 30-45 s on each stimulation zone. EFFECT: enhanced effectiveness of treatment.

Description

 The invention relates to medicine, in particular to cardiology, and can be used to treat various clinical variants of coronary heart disease.

 A known method of treating a patient with coronary heart disease (CHD) by combined laser therapy using a daily course of exposure to a low-intensity helium-neon laser (GNL) is first intravenous and then cutaneous in three cardiac zones of Zakharyin-Ged in combination with medications (ed. St. USSR of the USSR N 147356 AN 5/06. 1988).

The disadvantages of this method are as follows:
- in 30-35% of patients with coronary artery disease, the daily regime of GNL exposure to 40-45 min exposure at a radiation power of 1.5 mW at the end of the fiber leads to the development of a "secondary" exacerbation of the clinical manifestations of the disease;
- 20-25% of patients with coronary artery disease undergoing this treatment due to the presence of a number of pathobiological features in 4-5 sessions of GNL therapy of this regimen have hypercoagulation prethrombotic syndrome and / or a sharp increase against the initial level of deficiency of antioxidant reserves, which individually and more together, fraught with the most serious consequences;
- the first two positions, on the one hand, negatively affect the effectiveness of GNL therapy for patients with coronary artery disease, extend its course, and on the other, lead to a decrease in the use of the method (in particular, the restriction of the use in patients of the IV functional class (FC) , in severe continuous course of the disease, in persons older than 65-70 years of age, etc.)
An advantage of the invention is that the proposed complex of innovations makes it possible: to carry out GNL therapy for patients with coronary artery disease of any clinical forms, functional classes and types of course (stable, unstable, first-time, progressive, variant Prinzmetal, with exacerbation immediately after acute myocardial infarction); any age group, as well as with the above pathobiological features (presence of tendency to hypercoagulation, chronic DIC, antioxidant deficiency). In addition, the advantage consists in individualizing the duration of the course treatment, in reducing the duration, the total power of the laser exposure for each laser therapy session and, in general, on its course while maintaining high clinical and biological effectiveness and practically completely eliminating the "secondary" exacerbations and complications (clinical and biochemical), which ultimately expands the scope of application.

 The essence of the invention lies in the fact that, when combined with helium-neon laser therapy in combination with drugs, an IHD patient, in contrast to the prototype, is additionally injected with aspirin and devit during the entire course of treatment, and the number of intravenous, cutaneous GNL effects and their regimen moments (exposure procedures, the power or power density of the laser beam) is determined by the results of blood tests of the initial individual indicators of antithrombin-III (AT-III) and the dynamics of indicators of total antioxidant activity (AOA). In this case, intravenous exposure is carried out depending on the degree of decrease relative to the norm in the blood of AT-III after 1 or 2 days, in other cases - daily, but in all - with less exposure and laser exposure; and when stabilization of the maximum values of AOA for the patient is completed, the course of intravenous exposure is completed and transferred to the skin for 30-45 s per each exposure zone daily or every other day in accordance with the nature of the primary indicators of AT-III. The course of combined laser therapy is completed upon reaching the maximum clinical and biological effect for a particular patient.

 The treatment method is as follows.

 In a patient with coronary artery disease receiving traditional treatment with medications (nitrates, including prolonged, beta-blockers, calcium antagonists, etc.) for a disease that has arisen or worsened, the AT indicator is analyzed in the blood before starting a course of combined laser therapy in blood -III and when it decreases to a level of less than 50% relative to normal, intravenous GNL exposure sessions are carried out in two days, when reduced to values of more than 50% relative to normal, in one day, and in other cases, daily, for 10- 20 min at a radiation power at the end of the fiber of 1.0-1.5 mW. In addition, the AT-III indicator also serves as a determinant for doses of aspirin (in the range of 0.15-0.5 g / day) and Aevita (2-4 capsules of the official drug) additionally administered to the patient daily for the entire course of laser therapy.

Simultaneously with the analysis of AT-III in the blood, the AOA index is studied, the dynamics of which from the initially decreased values characteristic of patients with coronary heart disease to the maximum values for this patient with their subsequent stabilization and serves as an additional paraclinical individual criterion for completing the stage of intravenous exposure to GNL. At its end, they proceed to the stage of laser irradiation of the Zakharyin-Ged cardiac zones, which are carried out for 30-45 s for each exposure zone (the apex of the heart, the middle of the sternum, the left subscapular region) daily or every other day, depending on the initial indicators of AT-III ( beam power density 0.5 mW / cm ² ).

 Finish the course of laser therapy after individually achieving the maximum clinical and biochemical effect.

 The above boundary values of the modes of the proposed method of GNL therapy were established in a series of representative dynamic inpatient and outpatient, follow-up tests, including analysis of syndromological and clinical, biochemical parallels (including follow-up) in 274 patients with coronary artery disease (men and women in ages 34 to 76 years) of various functional classes (II-IV FC), various clinical forms (stable - 47, unstable - 192, progressive, first occurring, variant Prince-metal - 35) , with an exacerbation of the disease in the shortest possible time after acute myocardial infarction, over the age of 70 years, usually in the group of contraindications to GNL effects, as well as patients who are persistent for several years resistant to traditional drug treatment. Comparison was made with the known data of control studies of patients treated traditionally, as well as those who received undifferentiated laser therapy.

 The tests showed that the optimal exposure for intravenous GNL therapy procedures is an interval of 10-20 minutes, and the radiation power at the end of the fiber is 1.0-1.5 mW. At the same time, both the exposure time and the magnitude of its power are inversely dependent on the severity of the clinical manifestations of the disease, the severity of hypercoagulation shifts (degree of decrease in AT-III) and antioxidant deficiency (decrease in AOA) in the blood, as well as with an age over 65-70 years .

 A similar dependence, as it has been established, also submits to the operational positions of the subsequent stage of cutaneous GNL actions. At the same time, the regularity was revealed that the heavier the course of the disease and the severity of the complex of biochemical shifts, as well as the greater the age when the patient (65-70 years) received laser therapy, the lower the exposure (30 s per session) and the multiplicity (every other day) is necessary irradiate him with cardiac zones of Zakharyin-Ged. In other cases, this mode is 45 s daily.

, где Дж и Дп - соответственно оптическая плотность контроля и опыта (среднего по пробам контроля 1-4), V - объем плазмы β выражается в мл^-1. Уровень АОА у здоровых людей составил 0,66±0,13 мл^-1 (с колебаниями от 0,52 до 0,79).The choice of control biochemical parameters as reliable paraclinical criteria was also not accidental, because among the indicators characterizing the activity of the anticoagulant system (antithrombin factors), it is antithrombin III (which, when combined with heparin or alone, quickly or continuously deactivates thrombin) ; and the general state of antioxidant protection and its reserves reliably reflects such an integrative feature as the level of general antioxidant activity of the blood / 3 /. Antithrombin III was determined by the conventional enzymatic method (coagulological) of Ouchterloni, based on the ability (in terms of action) of the test blood plasma in comparison with the control to inactivate thrombin (the main coagulation factor) / 6 /); total antioxidant activity - according to the method based on the calculation of the degree of inhibition of lipid peroxidation in the suspension system of chicken egg yolk lipoproteins with the addition of different volumes of tested blood plasma samples, which is determined by the number of TBA-dependent products according to the formula; total AOA of blood (plasma) can be represented as a coefficient β equal to:

, where J and Dp are, respectively, the optical density of the control and experiment (the average for control samples 1-4), V is the plasma volume β expressed in ml ^-1 . The level of AOA in healthy people was 0.66 ± 0.13 ml ^-1 (with fluctuations from 0.52 to 0.79).

 The reliability of the selection of biochemical criteria is confirmed by a series of tests. Thus, it was shown that non-compliance with the “intermittent” (after 1 or 2 days) regimen of intravenous influences, depending on the degree of decrease in the blood level of the initial level of AT-III in a patient with coronary artery disease, is accompanied by a complicated “secondary” aggravation of the course of the disease and a complication of the treatment process due to the deepening hypercoagulable syndrome (repeated) with its clinical manifestations. In addition, it was found that failure to achieve stabilization in the blood of patients with AOA levels at the maximum values for a given patient (in fluctuations of ± 5-8%) is almost always accompanied by a “secondary” exacerbation during GNLT due to a “return” of the expressed AOA deficiency.

 Clinical trials with a dynamic analysis of these biochemical parameters have also established that the introduction of a patient with coronary artery disease receiving combined laser therapy with the protective purpose of one, albeit composite in composition antioxidant drug Aevit (vinamines A + E in the complex) does not always prevent the occurrence of a more or less pronounced , but always an undesirable exacerbation of the clinical manifestations of the disease (the phenomenon of "secondary" exacerbation). It is possible that this is due to the fact that this complex structural antioxidant, which is structurally physiological in nature, under the conditions of the previously established significant increase in the activity of lipid peroxidation (LPO) processes of biomembranes under the influence of GNL effects, cannot fully neutralize free and biologically aggressive "radicals during the overproduction of FLOOR Metabolites, which determine the" triggering "of the mechanisms of" secondary "exacerbation.

 In addition, it was found / 5 / that therapeutic doses of vitamin E, which is part of Leviticum, in some cases can inhibit the synthesis of prostaglandins that control platelet activity and vascular wall tone, which contributes to the development of hypercoagulation and spasmodic syndromes. The latter, along with hyperactivity of lipid peroxidation, are one of the important pathogenetic factors of exacerbation of coronary heart disease / 4 /.

 In this regard, it can be assumed that under these conditions, the combined use of pharmacologically therapeutic doses of Levite (2-4 official capsules of 1 ml of active substance) and relatively small doses of aspirin (0.15-0.5 g / day) will be more effective daily to correct the consequences of LPO hyperactivity on the background of GNL and to prevent a "secondary" exacerbation of coronary heart disease during combined laser therapy.

 A similar premise was made because, according to our data, the administration of only aspirin to the patient, known for its low-dose inhibiting properties on the aggregation activity of blood cells and the synthesis of prostaglandins of the named effect / 1, 2 /, does not prevent a “secondary” exacerbation of coronary heart disease during GNL treatments. Hence the idea of a high probability of a good cumulative protective effect of a combination of both drugs in the GNL therapy of patients with coronary artery disease. One cannot but point out that the postulate of the above assumption was the mutually potentiating action of the Levitic components (retinol and tocopherol). The same potentiation was expected from the composition - aspirin + Leviticus.

This assumption has been fully confirmed in clinical trials. At the same time, it was found that the doses of these drugs are closely correlated with the severity of the course of the disease and with the initial indicators of AT-III. So, with a decrease in AT-III to values less than 50% relative to the norm and in patients with IV-FC they are maximum in the indicated range (0.5 ⁺ 4 capsules / day, respectively) daily for the entire course of treatment; with a less significant decrease in AT-III, II-III-FC - minimal (0.15 + 2).

Example 1. Patient Peninsula N.I., 48 years old, was admitted to the cardiology department for angina attacks that began for the first time two days ago during the night's sleep (about 3 and 5 o’clock in the morning). The first and second time in emergency medical treatment the attacks were stopped with nitroglycerin, but the last time the effect was insufficient even after 10 tablets taken consecutively. He was hospitalized with suspicion of a first-occurring variant angina pectoris. The clinic noted a combination of vasospastic angina syndromes and typical exertional angina. Daily ECG monitoring revealed changes characteristic of Prinzmetal variant angina pectoris: signs of coronary artery spasm in the form of an ST segment elevation above the isoline, transmural changes and concomitant ventricular cardiac arrhythmias (transient extrasystole as bigeminia). In the coagulogram: increased fibrinogen - up to 532 mg%; a sharp decrease in AT-III - up to 43%; plasminogen - 3.9 KE / ml; fibrinogen B - (+); fibrin degradation products 12 μg / ml, i.e. there are biochemical phenomena of hypercoagulable prethrombotic syndrome. The level of AOA was, like AT-III, significantly reduced (0.31 ml ^-1 ). Along with the traditional use of cardiotropic and other medications, the patient began a course of combined helium-neon laser therapy (GNTL). Using the abovementioned clinical and biochemical criteria, the regimes of the stage of intravenous exposure were determined (according to the level of AT-III reduction - multiplicity after two days; the exposure of each procedure was 20 minutes, the radiation power at the end of the fiber was 1.0 mW), as well as the required doses of aspirin and Aevita for the entire course of treatment (respectively, daily 0.5 + 4 capsules of the official drug, 1 ml each). After the 3rd procedure of intravenous GNTL, the level of AOA in the blood increased to a normal value (0.69 ml ^-1 ), and then remained at approximately the same maximum values for the patient after the 4th procedure and on the 5th day of treatment (fluctuations ± 6 - 7%, i.e. within the error). In this regard, intravenous procedures after 4 sessions were discontinued. A significant improvement in the patient's condition, increased activity and general tone, and the disappearance of feelings of fear were noted. On the 5th day, the attacks of nocturnal angina and signs of spasm of the coronary vessels stopped during daily monitoring of the ECG; although residual signs of transmural changes in the myocardium continued to be detected (in Y ₄ - Y ₆ ); noted, but a single gastric extrasystole. Significantly (almost twice) the need for coronary-active drugs decreased. No clinical or biochemical signs of "secondary" exacerbation were observed. By this time, AOA remained at a stable level (0.72 ml ^-1 ); in a coagulogram - fibrinogen - 300 mg%; AT-III - 105%; plasminogen - 4.99 KE / ml; fibrinogen B - (-), which reflected the elimination of antioxidant deficiency and hypercoagulation syndrome. The GNTL course, in accordance with this, was continued by a stage of cutaneous laser irradiation on three known Zakharyin-Ged cardiac zones every other day for 30 s each (by a defocused beam with a power density in the irradiation region of 0.5 mW / cm ² ). 5 such procedures were performed. Attacks of angina pectoris completely stopped, pathology was not detected even during ECG monitoring. Ceased to need nitrates. No adverse effects of GNTL were detected. Three days after the control clinical and biochemical studies (AOA at a stable level - 0.67 ml ^-1 ; AT-III - 112%), the administration of aspirin was completed, and Aevita and the patient were discharged under outpatient supervision by a cardiologist. Follow-up after 6 - 9 - 12 months - lasting effect. The example demonstrates, firstly, the full compliance of the good therapeutic effect of the course combined laser therapy (clinical and biochemical) with the treatment regimen used; secondly, a fairly short total duration of therapy required to achieve this effect (with traditional treatment - at least 4 - 5 weeks.); thirdly, the absence of any GNL complicating moments (observed with this pathology under the GNTL prototype modes).

Example 2. Patient I. I, AM, 56 years old, was admitted to hospital for another exacerbation of coronary heart disease (unstable progressive angina pectoris, IV-FC, aortic atherosclerosis, atherosclerotic cardiosclerosis), which proceeds against the background of persistent resistance to traditional drug therapy. The duration of the disease is 8 years. It was found that at first cardiotropic drugs had a certain positive effect with achieving clinical (first two years), then only therapeutic (3-5 years) remission, and in subsequent years a therapeutically continuous course with frequent exacerbations requiring a hospital regimen was noted, and very short "bright" intervals (partial pharmacological remission with a fairly high need with an antianginal agent). A year ago, he suffered an acute transmural antero-lateral myocardial infarction. Currently, the introduction of even very significant doses of cardiotropic drugs of all three classes (nitroglycerin - up to 50 tablets per day against the background of sustac - 3 to 6 tablets, beta-blockers and calcium antagonists of various types) is unsuccessful (up to 20 - 30 or more attacks per day even at rest). Hospitalized purposefully for a course of laser therapy. The examination revealed occlusion of two coronary vessels (the left anterolateral part of the ventricle of the heart), as well as other data confirming the diagnosis and the need for combined GNTL. In blood tests, the phenomena of hypercoagulable syndrome were detected (with an average degree of AT-III reduction of up to 74%) and a sharp decrease in antioxidant protection (AOA was 0.35 ml ^-1 ). In accordance with the clinical and biochemical status (IV-FC), the following laser therapy regimes were determined: at the first stage, the multiplicity of intravenous procedures was every other day, the exposure of the session was 10 minutes with a beam power at the end of the fiber of 1.0 mW; at the same time, the introduction of aspirin and Aevit in a daily dose of 0.5 + 4 capsules of the official drug, respectively, over the entire course of treatment, was started. Dynamic analysis of AOA showed that its level increased (to 0.59 ml ^-1 ) and remained at a stable maximum level after 5 intravenous GNL treatment procedures (0.61; 0.66). Therefore, treatment taking into account a significant improvement in the patient’s general condition of a steady and significant reduction in angina attacks (up to 2–4 per day), as well as a decrease in the need for cardiotropic drugs (up to 5–8 tablets of nitroglycerin), a noticeable positive effect, also noted by the results of the study The ECG, the absence of any complications during the course of the disease, was continued by the stage of cutaneous exposure, to which (0.5 mW / cm ² ) the Zakharyin-Geda zones were tucked daily for 30 s each. After 7 such sessions, the attacks of the sternum were stopped (for the first time in many years), the patient's tolerance to physical activity increased, became quite active, the psychological status, tone and stability increased; ECG showed a significant improvement in coronary circulation in the previously ischemic myocardial region. The course of laser therapy in combination with the introduction of aspirin and Aevit is discontinued. Discharged under the supervision of a cardiologist at the minimum maintenance doses of coronary active agents. Follow-up after 6 and 9 months. - the therapeutic effect lasts, attacks did not resume, the dose of drugs did not increase. However, in accordance with the terms of therapeutic remission and anti-relapse GNTL, in spite of the quality of remission, it is recommended to conduct a shortened therapeutic and preventive course of laser therapy. The example demonstrates well on the "internal" control, which is the patient himself, the high result of the treatment according to the proposed regimes, the absence of consequences undesirable against the background of GNTL, the stability of the effect, the short duration of the course of laser therapy.

Example 3. Patient S. N. N., 49 years old, sick with coronary artery disease (angina pectoris, II-FC) for 3 years. Recently, angina attacks have become more frequent and stopped with an increasing number of coronary active drugs. He turned on an outpatient basis to determine the feasibility and feasibility of laser therapy. The diagnosis was confirmed clinically and paraclinically (in particular, with the help of ECG studies and bicycle ergometry), the formation of a pharmacotherapeutic resistance syndrome was observed. A decision was made on direct indications for combined GNTL in the clinic. The blood test revealed a normal level of AT-III (101%) with moderately reduced AOA (0.47 ml ^-1 ). The patient started the administration of aspirin and Aevit (0.25 g + 3 officinal capsules of 1 ml of a composite preparation of antioxidant vitamins). At the same time, under the control of AOA dynamics, a stage of intravenous exposure to GNL was carried out until the level of antioxidant protection (0.74 - 0.7 ml ^-1 ) was stabilized in the daily routine for 20 min each with a beam power of 1.5 mW at the end of the fiber (3 sessions at stabilization of the maximum level of AOA). Then the treatment was continued with 5 cutaneous procedures daily for 45 s per exposure zone (for 45 s at a power density of 0.5 mW / cm ² ). Complications, "secondary" exacerbations at both stages of GNTL were not noted. In connection with the complete restoration of drug sensitivity, the elimination of an attack of angina pectoris and pathological changes on the ECG, the restoration of normal exercise tolerance and working capacity, the course of combined laser therapy is completed. Follow-up - 12 months - the therapeutic effect is stable, the "non-drug" period continues. At present, he does not need anti-relapse laser therapy. The example demonstrates not only good performance with the sufficiency of a relatively short course of GNTL, but also the duration of the therapeutic effect of the application of helium-neon laser therapy regimes previously developed in clinical trials in its combined form and in combination with aspirin and Aevit performed on an outpatient basis.

Example 4. Patient R. Ya. F.S., 52 years old, was hospitalized for exacerbation of coronary heart disease (unstable angina, III-FC) with the presence of already formed pharmacoresistance to coronary active agents. When conducting intravenous laser therapy (20 min, 1.5 mW daily) already at the 3rd GNTL procedure with the simultaneous administration of aspirin and Aevit (0.15 + 2 officinal capsules), a good clinical effect was achieved in the form of reducing angina attacks and doses of cardiotropic drugs, a significant increase in the level of AOA was noted, initially significantly reduced (0.64 and 0.45 ml ^-1, respectively). Indicator AT-III was within normal limits. The procedures of intravenous exposure, it was decided to stop, considering the patient's antioxidant reserve sufficiently restored, and begin the stage of cutaneous procedures. However, on the second day after the first session of irradiation of the Zakharyin-Ged zones (in a regime of 45 s for each exposure zone daily at a power density of 0.5 mW / cm ² ), a “secondary” exacerbation occurred in the form of a newly increased increase in angina attacks with an increased need for coronary drugs. The control blood test again revealed a significant decrease in blood levels of AOA (0.33 ml ^-1 , which is even lower than the initial value); AT-III remained stable (98%). Percutaneous therapy was discontinued due to the well-founded opinion that the cause of this "exacerbation" was a sharp repeated decrease in antioxidant protection due to the lack of reduction of AOA to a stable maximum level for the patient (possibly with an insufficiently sufficient dose of aspirin and Aevit). A short break was made (3 days for dynamic monitoring and resolving the issue of further treatment tactics0. Then, the stage of intravenous exposure was again started, but, of course, with a change in the GNTL regimen. The exposure to the procedure was determined at 15 min at a power of 1.0 mW, and later 1, 5 mW, taking into account the possibility of repeated overdose, with the composition of aspirin + Aevit - 0.3 + 3 capsules.After 3 such sessions, the level of AOA again increased, but stabilized at a maximum value after another 3 sessions (AOA - 0.66; 0.7 ; 0.65 ml ^-1 ), when further intravenous exposure would However, AOA remained stable. Clinical improvement progressed at the usual pace for such patients. It was prescribed in good condition with minimal doses of drugs. Catamnesis - 3 months, does not take medications, angina attacks no, 8 months - the condition is stable. Monitoring continues. The example demonstrates, on the one hand, that failure to achieve stabilization of the maximum level of AOA for the patient at the intravenous stage th GNTL fraught with "secondary" aggravation that lengthens and complicates the treatment process; and, on the other hand, that even under these conditions, by using the correct regimen moments, it is possible to achieve the “restoration” of the proper therapeutic effect of GNTL; third, the need to comply with the proposed regimes and at the same time their fidelity.

Such “negative” examples had to be encountered when working out all the above regimen moments of the proposed GNTL method in its combined version (referring to the dosage of aspirin and Aenit, the duration of their administration, the duration, the power of GNL effects at various levels of AOA and AT-III, FC patients, etc.)
The general conclusion from the given clinical examples is the confirmation of the advantages that the proposed method has in relation to the prototype, i.e., uncontrolled laser therapy taking into account the dynamics of paraclinical parameters relative to the initial values in specific patients. In particular, in addition to individualizing the choice of regimen and the duration of GNLT stages, a general reduction in the duration of its course is provided with high therapeutic efficacy, proven history and in the almost complete absence of "secondary" complications.

The technical and economic efficiency of the proposed method is determined by two main positions:
- simplicity of execution, which does not require any special methodological techniques or modifications, involving the use of well-known serial laser equipment of domestic production and not only not costly, but giving an economic effect;
- the emergence of a basic in its essence and unified in terms of use method of treating patients with coronary artery disease, providing a long-term therapeutic effect in any clinical form and type of disease course.

 Follow-up analysis showed that, in general, the duration of therapeutic remission (which can often be achieved in a patient who is resistant to cardiopharmacological drugs for a long time) —a leading indicator of the therapeutic effect of any proposed method — even with a single course of such combined differentiated laser therapy with an individual selection of GNTL modes increases prototype approximately 1.5 - 1.7 times. Negative results (immediate and separated) were not noted.

Literature
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Claims (1)

 A method of treating coronary heart disease, including combined intravenous and cutaneous helium-neon laser therapy in combination with medications, characterized in that the patient is additionally injected with aspirin at a dose of 0.15-0.5 g, Aevit at a dose of 2-4 capsules daily for the entire course of treatment, in addition, the initial indicator of antithrombin-III and the level of total antioxidant activity before and during intravenous procedures and with a decrease in the level of antithrombin-III relative to normal intravenous Exposure is carried out after 1 - 2 days for 10 - 20 minutes with a radiation power at the end of the fiber of 1.0 - 1.5 mW, in other cases, sessions are carried out daily, and when the maximum values of the level of antioxidant activity are stabilized, intravenous exposure is completed and transferred to the skin procedures for 40 - 45 s per exposure zone daily or every other day.