RU2480206C1 - Method of immunocorrection of main course of treatment of destructive forms of pulmonary tuberculosis - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to phthisiology and can be used with the purpose to increase efficiency of treatment of patients with destructive forms of pulmonary tuberculosis. For this purpose after relief of intoxication manifestations and absence of side effects thymaline in dose 40 mg is introduced to patient in paravasal way 5 days running. After that, 6 days after finishing its introduction, 3% solution of drug glutoxime is introduced in dose 2.0 ml for 10 days. Then, introduced is cycloferon in dose 0.25 g, two times per week until intensive stage of main course is over.

EFFECT: invention makes it possible to reduce terms of elimination of destructive changes in lungs and achieve cessation of mycobacteria release in patients with expressed secondary immunodeficiency.

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Description

The invention relates to medicine, namely to TB, and can be used to treat patients with destructive forms of pulmonary tuberculosis.

It is known that the acute and progressive course of tuberculosis, which is difficult to treat with anti-TB drugs, is largely due to dysfunctions of the immune system. It is generally accepted that in case of impaired immunity, by acting on its individual link with immunocorrectors, it is ultimately possible to change the functional activity of the entire immune system (Petrov R.V., Khaitov P.M.). However, in diseases, unlike healthy people, due to violation of cooperation, the interconnection of different parts of the immune system is violated, therefore, correction of one part of the immune system can not always lead to the restoration of the sanogenetic orientation on the part of others. This may explain the ineffectiveness of immune-correcting therapy in septic conditions, when they affect mainly the monocytic-macrophage immunity. If at the same time you do not act on the infectious agent, clinical cure is unlikely.

In patients with destructive forms of pulmonary tuberculosis in the presence of numerous antigens and populations of mycobacterium tuberculosis in the body, the insufficiency of the cellular immune response is manifested by a decrease in the relative number of CD3-, CD4-, CD8-lymphocytes, CD4 / CD8 index, as well as monocytes expressing histocompatibility class II antigens. Along with cellular immunodeficiency, there is almost always an increase in the humoral immunity in the form of an increase in the number of B-lymphocytes and an increase in the synthesis of anti-tuberculosis antibodies and immunoglobulins of classes A, G, M, which is due to the strong antigenic properties of mycobacterium tuberculosis.

For the purpose of immunostimulation and immunocorrection in the treatment of tuberculosis, as well as other infectious diseases, various immunostimulants are used in various combinations (ionizing radiation, thymalin and others). So, in the experiment, tuberculosis was treated in animals infected with M. tuberculosis that are resistant to isoniazid, rifampicin or ethambutol (Vinogradova T.I., Zabolotnykh N.V., Vitovskaya M.L., Vasilieva S.N., Ariel B.M. Experimental multidrug-resistant tuberculosis: optimal treatment regimens. // Tuberculosis in Russia, year 2007. Materials of the 7th Russian Congress of TB Specialists. Moscow. 2007 - p. 95-96) with various combinations of 4 antibacterial drugs, mainly of the reserve series, and at the same time other drugs were administered to animals VA glutoxim, bestim, islacet and especially perchlozan. Cycloferon was used to moderate activation of stress-implementing systems in case of tuberculosis (T. Filipova. Pathogenetically directed correction of adaptive reactions of the body in the treatment of patients with secondary forms of pulmonary tuberculosis. // Abstract of dissertation for the degree of Doctor of Medical Sciences, M., 2009 )

The closest prototype is a method of immunostimulation and immunocorrection in tuberculosis using an immunostimulant (Maslennikov A.A., Pogorov V.N., Kolomiyets V.M. Method of immunological correction for progressive forms of pulmonary tuberculosis. // Problems of tuberculosis, - 2007, - № 9. - P.30-33), when one immunostimulator is used, administered lymphotropically, followed by stimulation of the monocytic-macrophage system with the metabolic immunomodulator glutoxim. However, with the proposed method, immunocorrectors do not potentiate the effect of each other, the course of treatment is short, while etiotropic therapy in the intensive phase lasts at least two months.

The technical result is to increase the effectiveness of treatment of patients with destructive forms of pulmonary tuberculosis while reducing the time to eliminate destructive changes and bacterial excretion.

The technical result is achieved by the fact that after withdrawal of the manifestations of intoxication and in the absence of adverse reactions to anti-TB drugs, thymalin is administered paravasally to the patient at a dose of 40 mg for 5 consecutive days, then 6 days after the end of its administration, a 3% glutoxim solution is administered in a dose of 2.0 ml, for 10 days, and then cycloferon in a dose of 0.25 g twice a week until the end of the intensive phase of the main course of treatment.

The method is as follows. Before starting the main course of treatment with standard modes of antituberculosis drugs, the initial immune status is determined during clinical and immunological examination. After the removal of symptoms of intoxication, the absence of adverse reactions to anti-TB drugs and a positive prognosis in the restoration of immunological status, paravasal lymphotropic immunocorrection is carried out in stages, taking into account the principle of hierarchical immune system. The goal of the first stage is to restore the T-system of immunity, in the second stage they act on the monocytic-macrophage immunity. At the first stage, thymomimetic, a hormone of the central organ of the immune system, thymalin is used. Given the presence in the body of substances capable of inhibiting thymus hormones, thymalin is administered in large doses, at least 40 mg per day, once. After 3-6 days, depending on the clinical situation in the patient, the monocytic-macrophage system is stimulated by the metabolic immunomodulator in the second stage. For this purpose, glutoxim 3% solution of 2 ml is introduced, for 10 days a representative of a new class of drugs - thiopoietins, which have a modulating effect on intracellular processes (thiol metabolism) and which have the effects of systemic cytoprotectors. Immunotropic drugs were dissolved in 5 ml of 0.25% novocaine and injected into the first intercarpal or intertarsal gap of both limbs to a depth of 1.5-2.0 cm (in the direction from their center to the rear).

The introduction of the claimed combination of drugs paravasally lymphotropically ensures their transport directly into the lymphatic flow, followed by entry into the system of peripheral organs of immunogenesis, presenting the possibility of exerting a regulatory effect on immunocompetent cells directly in the phase of the formation of functional activity. Further, under the control of adaptive immunity indicators, it continues to be corrected with cycloferon, which, as a low molecular weight inducer, induces high titers of interferon in organs and tissues containing lymphoid elements (spleen, liver, lungs), activates bone marrow stem cells and, stimulating the formation of granulocytes, natural killer and cells of the T-system, normalizes the balance between subpopulations of T-helpers and T-suppressors. Cycloferon is administered intramuscularly or orally at a dose of 0.25 g twice a week for two months until the end of the intensive phase of the main course of treatment, for a total of 4-5 g.

For an example of the effectiveness of the proposed method, it is possible to present a clinical example.

Patient A., was admitted to the therapeutic department of OGUZ “Tuberculosis dispensary” with a diagnosis of infiltrative tuberculosis of the left lung phase of MBT decay (+), resistance to rifampicin and streptomycin; relapse (early). Prior to this, she was treated in a number of other TB departments of the region and Central Research Institute of RAMS, Moscow. Despite adequate anti-tuberculosis therapy, intoxication persisted and there was no tendency to scarring of destructive changes. Received with complaints of weakness, shortness of breath, fever up to 38.2 ° C, cough with sputum. In the immunogram: against the background of a decrease in cellular immunity and the phagocytic index, there is an increase in the CEC and indicators of humoral immunity.

An X-ray examination: in S2 of the left lung, a cavity up to 4.5 cm in diameter is noted, the walls are infiltrated. In the remaining parts of the lung, against the background of dense foci, multiple focal and infiltrative changes. Hemogram: Er - 3.2; HB - 97.4p-0.8; 8.6; e - 3; P - 2; C - 70; lf - 15; m - 5; ESR - -43 mm / h.

The patient was prescribed thymus preparations thymalin as a pathogenetic therapy.

A drug from a number of glucocorticoids - dexamethasone

Lymphotropic drug - novocaine

The entered volume is 10 ml

The number of introductions - 7

The interval between administration is one day.

The injection site is intramuscularly in the lateral square of the gluteal region, which does not correspond to the claimed method at the injection site.

There is no clinical effect.

Symptoms of intoxication persisted.

At the next stage, the same patient continued treatment according to the proposed method with the implementation of paravasal lymphotropic administration according to the claimed method by injection into the first intercarpal space of both hands.

Into each carpal space was introduced:

Thymus preparation - thymalin 40 mg,

The drug from a number of glucocorticoids - dexamethasone - 4 mg

Lymphotropic drug - novocaine - 0.25% solution

The injected volume is 10 ml.

Depth of introduction 0.5-1.5 cm

The number of introductions - 5

Interval between administrations, days - 1

Positive clinical effect was not observed.

After 6 days, after completion of the administration of thymalin, glutoxim, soluble in novocaine, was injected in pairs by injection into the first intercarpal space at a dose of 2.0 ml - 3% solution - 10 days.

After the course of paravasal lymphotropic administration of glutoxim was completed, subsequent immunocorrection with cycloferon at a dose of 0.25 g twice a week was carried out until the end of the intensive phase of the main course of treatment. Received a positive clinical effect. Within two days after the first injection, the patient's condition improved, body temperature returned to normal, weakness disappeared, shortness of breath stopped, and the number of wheezing in the lungs sharply decreased. After 2 months, the cavity healed.

The study was performed on 74 patients with the first detected destructive forms of pulmonary tuberculosis (infiltrative, disseminated, caseous pneumonia). In the control group, 36 people took only anti-TB drugs according to standard regimens (group I), 38 took anti-TB drugs according to individual regimens along with paravasal immunocorrection (group 2). Before starting the main course of treatment, 85% of the observed had a decrease in the initial state of immunity.

During treatment, a significantly large number of treatment failures after the end of the intensive phase in the elimination of intoxication in 31.6%, scarring of the cavities in 65.8%, and sputum negativity in 47.4% of cases were noted in patients of the control group. In patients of the 2nd group, after the end of the intensive phase of chemotherapy, only in 5.2% of cases, destructive changes in the lungs persisted and only in 2.6% of cases sputum negation was not achieved.

Thus, the proposed method for immunocorrection of the main course of treatment of destructive forms of pulmonary tuberculosis allows to achieve significant clinical improvement in the intensive phase of treatment, thereby reducing the time of its inpatient phase, to achieve clinical cure with the elimination of destructive changes and stopping the release of mycobacteria in a timely manner in people with secondary expressed immunodeficiency. As a result, the epidemic danger is reduced and the risk of disease recurrence is reduced.

Claims (1)

The method of immunocorrection of the main course of treatment of destructive forms of pulmonary tuberculosis, characterized in that after removing the manifestations of intoxication and the absence of adverse reactions to anti-TB drugs, thymalin is administered paravasally to the patient at a dose of 40 mg, 5 days in a row, then 6% after the end of its administration, 3% are administered - a solution of glutoxim at a dose of 2.0 ml, for 10 days, and then cycloferon at a dose of 0.25 g, twice a week until the end of the intensive phase of the main course of treatment.