RU2450820C2 - Method of treating destructive pulmonary tuberculosis - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely therapy of pulmonary tuberculosis. A method of treating pulmonary tuberculosis consists in introducing Bestim with underlying anti-tuberculosis preparations, and Bestim is introduced intratracheally in dose 1.0 mg 3 times a week; total therapeutic course makes 6 introductions. The preparation escaping a liver gets in the beginning to lungs and stays there for some time due to an ability of interstitial pulmonary tissue to keep medical substances quickly absorbed in pulmonary tissue. The efficacy of the integrated anti-tuberculosis treatment involving the intratracheal introduction of Bestim is increased: within the time limits to 2 months during an intensive phase of chemotherapy bacterioexcretion is terminated in 90.9 % vs. 50.1 % of control group (p<0.01) and the cavities are closed 50.0 % of patients vs. 27.0 % of control group. The main group shows 100% recovery of nonspecific endobronchitis. A cytokine imbalance is restored due to decreasing levels of proinflammatory cytokines (α -TNF (p <0.05) and γ-interferon), tends to increasing a level of anti-inflammatory cytokine IL-4.

EFFECT: method provides fast absorption of the preparation Bestim and delivery first of all into the lymphatic pulmonary system, then into the lesser circulation and only then into the greater circulation.

Description

The invention relates to medicine, namely pulmonology, phthisiology, can be used to treat destructive pulmonary tuberculosis.

Known methods of treating pulmonary tuberculosis with endobronchial administration of drugs.

The advantages of endobronchial administration of drugs for pulmonary tuberculosis were described as early as the 70s. So, A.E. Rabukhin noted that with such a delivery of the drug, the direct effect of the drugs on the mucous membrane of the respiratory tract, the walls of the alveoli, the pyogenic membrane of the cavity, and therefore on the vegetative pathogenic microbes with an increase in the concentration of the drug in the lungs and blood and regression of inflammation, is achieved in the walls of the bronchi and in the lung tissue. In particular, endobronchial administration of drugs is indicated for destructive tuberculosis with concomitant non-specific endobronchitis.

The easiest way is inhalation, however, a significant amount of the inhaled medicinal substance is lost - up to 70% (Krasnova T.K., Kim A.Ch., Nevekina V.A., 1982).

Another way is a doctor-bronchologist conducting treatment and rehabilitation fibrobronchoscopy with the introduction of drugs directly into the corresponding bronchus, but this method is technically more time-consuming.

There is a method of using a synthetic immunomodulator Bestim for the treatment of pulmonary tuberculosis - "A method for the treatment of pulmonary tuberculosis" (RF patent No. 2229892 from 06/08/2004). In this case, bestim is administered at a dose of 0.1 mg intramuscularly, the course of treatment is 5 injections. However, there is no data on the cure of a concomitant disease - nonspecific endobronchitis.

With the above method of administering bestim - v / m - in pharmaceutically permitted doses, the drug enters the tissues of the mucous membrane of the respiratory tract, passing through the large and small circles of blood circulation. Also, these routes of administration do not take into account the good absorption of the mucous membrane of the respiratory tract, which is associated with the thinness of the epithelium in the bronchi and trachea, a large number of blood and lymph vessels in the tracheobronchial tree, as indicated in 1907 by A. Galebsky. (Shesterina M.V., 1958).

We propose the intratracheal administration of a bestim synthetic immunomodulator. The medicine, administered intratracheally, quickly absorbed, enters, first of all, in the lymphatic system of the lungs, then in the pulmonary circulation and only after that in the big circle. Thus, the drug, bypassing the liver, first enters the lungs and stays there for some time due to the ability of the interstitial tissue of the lung to retain medicinal substances (Shesterina M.V., 1958).

The aim of the invention is to increase the effectiveness of etiotropic anti-tuberculosis therapy of destructive pulmonary tuberculosis, complicated by non-specific endobronchitis.

This goal is achieved by the introduction of the bestim immunomodulator in a dose of 1.0 mg, diluted with 2.0 ml of a 0.9% NaCl solution, intratracheally 3 times a week after 1 day for 2 days into the anti-TB chemotherapy regimen taking into account the drug resistance of Mycobacterium tuberculosis (MBT) weeks, general course - 6 introductions.

Treatment is carried out according to the following scheme: intratracheal administration of bestim at a dose of 1.0 mg per 2.0 ml of a 0.9% NaCl solution 3 times a week every other day is connected to the intensive phase of the corresponding drug sensitivity of the MBT chemotherapy regimen, for a total of 6 administrations.

Comprehensive treatment with anti-tuberculosis chemotherapy and a bestim immunomodulator was prescribed to 27 patients with newly diagnosed destructive pulmonary tuberculosis aged 19 to 59 years (they constituted the main group). Patients in the control group (20) were comparable in form of the disease with the main group and received anti-tuberculosis chemotherapy without a bestim immunomodulator. The therapeutic effectiveness of the method was evaluated based on the main indicators of the effectiveness of anti-tuberculosis therapy (abacillation, closure of decay cavities) and immunological data (T-lymphocytes, anti-inflammatory and pro-inflammatory cytokines - IL-4, γ-interferon, α-TNF).

In 76% of cases, an infiltrative process was diagnosed, in the rest - a disseminated process, in 84% of cases mycobacterium tuberculosis (MBT) was found in sputum. Studies were conducted in two groups. Patients of group I against the background of standard anti-tuberculosis chemotherapy, taking into account the drug resistance of the office, received bestim inhaled 3 times a week (every other day) - 6 injections; group II patients were prescribed a similar treatment with standard chemotherapy regimens.

Statistical processing was performed to determine the reliability of student results.

The cessation of bacterial excretion by the end of 2 months was found in 90.9% of patients of group I, while in patients of group II only in 50.1% of cases. Closure of the decay cavities for this period of time was observed in half the cases among patients of group I and in 27% in patients of group II. In all cases, the treatment of nonspecific endobronchitis was diagnosed in patients of group I by the end of the first month of treatment, while in patients of group II, treatment of endobronchitis occurred at a later date - after 1.5-2 months.

In the study of cytokine imbalance, data were obtained. In patients of group I, at the end of the intensive phase of chemotherapy, a significant increase in the number of lymphocytes was detected (p <0.05) with an average value of 33.2 ± 3.7. There was no significant effect on the levels of IL-4 and γ-interferon, however, there was a tendency to normalize their levels. Moreover, against the background of the use of bestim in patients of group I, the level of the pro-inflammatory cytokine α-TNF significantly decreased (p <0.05).

Table 1 Dynamics of cessation of bacterial excretion and closure of decay cavities Observation group The termination of bacterial excretion by the end of 2 months Closure of decay cavities by the end of 2 months The cure of non-specific endobronchitis Main 90.9% * 50.0% 100% after 1 month Control 50.1% 27.0% 100% after 2 months Note: * - p <0.01.

Conclusion: the use of bestim against the background of standard chemotherapy can increase the effectiveness of treatment - in a short time (2 months) during the intensive phase of chemotherapy to achieve the cessation of bacterial excretion (90.9% of cases, p <0.01), closure of decay cavities (50.0% ), cure non-specific endobronchitis in 100% of cases, eliminate cytokine imbalance due to lower levels of pro-inflammatory cytokines (α-TNF (p <0.05) and γ-interferon), a tendency to increase the level of anti-inflammatory cytokine IL-4.

Clinical example.

Patient S., 27 years old, was hospitalized in the pulmonary tuberculosis department of the Scientific and Practical Center "Phthisiology", was identified by reversibility as FLH +.

Upon admission, a clinical diagnosis was made - infiltrative tuberculosis of the upper lobe of the right lung in the decay phase, MBT +, drug resistance to S 5γ, H5γ.

The condition at admission is satisfactory, complained of general weakness. In the OAK of 09/26/06: red blood cells 4.49, hemoglobin 144, white blood cells 5.7, s / I 66.0, lymphocytes 27.0, ESR 27 mm / h. In sputum smear microscopy 3 times revealed KUM - 2+. Sputum culture at the Office from 09/27/06 - 09/08/06 - 20-100 CFU. The resistance of MVT from 09.06 is to S 5γ. Conclusion FBS upon admission - catarrhal endobronchitis II degree of inflammation. On the Rg-mm of the chest organs from 10/05/06, inhomogeneous dimming is determined on the right in the upper lobe due to pronounced infiltration in S ₁ -S ₂ with the presence of a decay cavity of d-1.3 cm, in S ₃ - foci, S ₆ - infiltration site with a decay cavity of d-2.0 cm, the right root is widened (Fig. 1).

The patient was assigned the I chemotherapy regimen H, R, S, Z, and a month after the start of treatment, intratracheal administration of bestim was connected. After 2 months of treatment (intensive phase) with intratracheal administration of bestim at a dose of 1.0 mg three times a week, the course dose was 6 injections. X-ray positive dynamics is observed in the form of a noticeable resorption of infiltration in the upper lobe of the right lung, a significant reduction in the decay cavity in size, the cessation of bacterial excretion after 1.5 months (confirmed by seeding). According to FBS, 1.5 months after the start of treatment, a cure for catarrhal endobronchitis is noted. Radiological - 2 months after chest x-ray, complete resorption of infiltration and closure of the decay cavity is observed (Fig. 2). The patient was discharged for outpatient treatment.

As a result of the application of the method of treating destructive pulmonary tuberculosis by intratracheal administration of bestim, it became possible to increase the effectiveness of treating tuberculosis by reducing the termination of bacterial excretion and closing the decay cavities during the intensive phase of chemotherapy - 2 months, to cure catarrhal endobronchitis, and eliminate cytokine imbalance.

Claims (1)

A method of treating pulmonary tuberculosis by administering bestim against the background of anti-tuberculosis drugs, characterized in that bestim is administered intratracheally at a dose of 1.0 mg 3 times a week, the general course of treatment is 6 injections.

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