RU2621875C1 - Method of treating patients suffering pulmonary tuberculosis - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: antibacterial therapy is conducted in accordance to standard conditions. From the first day of treatment, also inject Wobenzym daily 1 tablet 30 minutes before meals 2 times a day for 60 days. Additionally, 10 intravenous drip infusions of the drug Reamberin are included in the course of treatment from the first day. Infusions are performed once a day every other day at a dose of 400 ml per infusion.

EFFECT: reduction of the periods of resorption of infiltration, closure of cavities of decay, abacillation, reduction in the frequency of formation of adverse hepatotoxic reactions.

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Description

The invention relates to medicine, namely to phthisiology, and can be used in the complex treatment of patients with pulmonary tuberculosis.

The use of pathogenetic agents is one of the most important stages in the treatment of patients, which allows to accelerate the reverse development of inflammation, stimulate reparative processes in the body, and also prevent the occurrence of toxic toxic reactions to antibacterial drugs. Intoxication, the presence of concomitant diseases, hypoxia contribute to the excessive activation of lipid peroxidation and the suppression of antioxidant defense systems. An increase in the concentration of oxygen free radicals damaging the cells is clinically manifested by the rapid progression of the process, the appearance of destruction in the lung tissue, and also lead to a deep impairment of liver function, which creates the background for the occurrence of hepatotoxic reactions (M. Guryleva, Tuberculosis and liver diseases // Phthisiology (national leadership) - M .: GEOTAR-Media, 2007. - S. 349-351). Strengthening the processes of free radical oxidation contributes to intensive collagen formation and the formation of fibrotic changes in the lung tissue, which enhances hypoxia, reduces the bioavailability of antibacterial drugs and leads to a chronic tuberculosis process (Menshchikova EB et al. Oxidative stress: Pathological conditions and diseases. - Novosibirsk : ARTA, 2008 .-- S. 122-129).

The main method of treatment for patients with pulmonary tuberculosis is a course of antibacterial therapy according to standard modes, which is regulated by order of the Ministry of Health of the Russian Federation No. 951 dated December 29, 2014 "On approval of methodological recommendations for improving the diagnosis and treatment of respiratory tuberculosis."

The disadvantages of the course of antibacterial therapy according to standard modes are: lack of effectiveness in relation to resorption of infiltration, closure of cavities and abacillation, the frequent formation of adverse hepatotoxic reactions.

This makes it necessary to develop new highly effective methods of treating patients with pulmonary tuberculosis, with the help of which it would be possible to avoid the above disadvantages and increase the effectiveness of treatment.

A search for scientific, medical and patent literature found various methods of treating patients with pulmonary tuberculosis.

So, Ivanov A.K., Sologub T.V. et al. (Tuberculosis: peculiarities of the course, possibilities of pharmacotherapy // Textbook for doctors. - St. Petersburg, 2009 - pp. 71-77) a method for the treatment of tuberculosis patients is proposed, in which, in addition to the course of antibiotic therapy, according to standard modes, is prescribed Cycloferon preparation according to the scheme - 0.6 g once peros in 1, 2, 4, 6, 8, 11, 14, 17, 20, 23rd days from the start of treatment.

In the work of Arshinova S.S. and Pinegin B.V. “Immunomodulators in the treatment of patients with active pulmonary tuberculosis” (The Physician, 2002, No. 10, pp. 36-37) describes a method for the treatment of pulmonary tuberculosis patients, which includes the inclusion of antibiotic therapy according to the standard regimen of the drug Polyoxidonium, which is prescribed 6 mg IM twice a week, 10 injections per course.

RF patent No. 2088231 (published on 08.27.1997) protected the "Method for the treatment of pulmonary tuberculosis", which provides for the appointment of a patient in addition to the course of antibacterial therapy according to the standard regimen of Xymedon inside, at a dose of 2 g four times a day for two months.

RF patent No. 2323739 (published May 10, 2008) protects the “Method for the treatment of patients with pulmonary tuberculosis”, which provides for the appointment of 1 tablet 3 times a day 30 minutes before meals, in addition to the course of antibiotic therapy according to standard modes, from the first day of Wobenzym, daily for the entire period of treatment and daily DENS therapy - percutaneous electroneurostimulation in the direct projection of the lungs over the area of the pathological focus and in the central universal zone - along the midline, right and left paravertebral lines, in comfortable energy mode with a frequency of 77 Hz, a total duration of exposure of 30-35 minutes and a course of treatment of 20 sessions.

RF patent No. 2456006 (published July 20, 2012) protected the “Method of treating patients with pulmonary tuberculosis”, which provides for the appointment of a patient in addition to the course of antibiotic therapy according to the standard regimen of probiotic dietary supplement SimBiovital 9.0 g once, every other day, during administration food for two months, as well as the Hepel preparation, 1 tablet 1 time per day sublingually, daily for four months.

The disadvantage of all the above methods of treating patients with pulmonary tuberculosis is the lack of effectiveness with respect to the timing of resorption of infiltration, closure of decay cavities and abacillation, and the frequent formation of adverse hepatotoxic reactions.

The closest in essence and taken as a prototype is the "Method for the treatment of patients with pulmonary tuberculosis", protected by RF patent No. 2318515 (published on March 10, 2008), which provides for antibiotic therapy according to standard modes with the introduction of Wobenzym orally from the first day of treatment daily 1 tablet 30 minutes before meals. The drug Wobenzym is administered to the patient 3 times a day for 4 months. Additionally, homeopathic medicines are administered to the patient - apis mellifika 6, quin officinalis 6, helidonium mayus 6, stannum 6, sanguinarium canadensis 6, potassium bichromicum 6, carbo vegetabilis 6 5 grains 3 times a day, regardless of food intake daily for the entire treatment period.

The disadvantage of the prototype is the limitation of the contingent of patients who agree to the use of homeopathic medicines, its lack of effectiveness with respect to the timing of resorption of infiltration, closure of decay cavities, abacillation, as well as the possible formation of adverse hepatotoxic reactions. We identified these shortcomings as a result of a retrospective analysis of 20 case histories of patients with pulmonary tuberculosis, the treatment of which was carried out according to the prototype in the pulmonary department of the State Budgetary Institution of the Rostov Region "Tuberculosis Clinical Dispensary" (GBU RO PTKD).

The objective of the invention is to develop a highly effective method for the treatment of patients with pulmonary tuberculosis.

The technical result is to increase the effectiveness of treatment, namely: reducing the time of resorption of infiltration, closing decay cavities, abacillation, as well as reducing the frequency of adverse hepatotoxic reactions.

The technical result is achieved by assigning a patient a course of antibacterial therapy according to standard modes. From the first day of treatment, the patient is orally administered Wobenzym for 60 days daily, 1 tablet 2 times a day 30 minutes before meals. In addition, from the first day, 10 infusions of Reamberin are included in the course of treatment, which are administered to the patient once a day every other day intravenously in a dose of 400 ml per infusion. After 60 days from the start of treatment, Wobenzym is canceled, and the course of antibiotic therapy according to standard modes is continued.

Reamberin (registration number P No. 001048/01). Dosage form - solution for infusion of 1.5% in bottles of 100, 200 and 400 ml or in plastic containers of 250 or 500 ml. One liter contains: meglumine sodium succinate - 15.0 g, obtained according to the following prescription: N-methylglucamine (meglumine) - 8.725 g, succinic acid - 5.280 g; excipients: sodium chloride - 6.0 g, potassium chloride - 0.30 g, magnesium chloride (in terms of anhydrous) - 0.12 g, sodium hydroxide - 1.788 g, water for injection up to 1.0 l. Reamberin has an antihypoxic and antioxidant effect, having a positive effect on aerobic processes in the cell, reducing the production of free radicals and restoring the energy potential of cells. The drug activates the enzymatic processes of the Krebs cycle and promotes the utilization of fatty acids and glucose by cells, normalizes the acid-base balance and the gas composition of the blood.

Wobenzym (registration number P No. 011530/01) is a combination of natural highly active enzymes of plant and animal origin. Dosage form - enteric coated tablets. One tablet contains active substances: pancreatin 345 prot. IU EF, papain 90 IU (FIP), rutosidate trihydrate 50 mg, bromelain 225 IU (FIP), trypsin 360 IU (FIP), lipase 34 IU (FIP), amylase 50 IU (FIP), chymotrypsin 300 IU (FI). Wobenzym has an immunomodulatory, anti-inflammatory, fibrinolytic, decongestant, antiaggregant and secondary analgesic effect. It has a positive effect on the course of the inflammatory process, limits the pathological manifestations of autoimmune and immunocomplex processes, positively affects the immunological reactivity of the body. It stimulates and regulates the functional activity of macrophage monocytes, natural killer cells, stimulates antitumor immunity, cytotoxic T-lymphocytes, and phagocytic cell activity. Under the influence of Wobenzym, the number of circulating immune complexes decreases and membrane deposits of immune complexes are eliminated from the tissues. Wobenzym reduces interstitial plasma cell infiltration. It increases the elimination of protein detritus and fibrin deposits in the inflammation zone, accelerates the lysis of toxic metabolic products and dying tissues, improves resorption of hematomas and edema, and normalizes the permeability of blood vessels. Wobenzym increases the effectiveness of antibiotic therapy by increasing the concentration of antibiotics in the blood plasma and the focus of inflammation, and also reduces the side effects of antibiotics, such as dysbiosis. Regulates the mechanisms of nonspecific protection, the production of interferons, thereby exhibiting antiviral and antimicrobial effects.

The practical feasibility of the claimed method is illustrated by examples from clinical practice:

Example 1: patient A., 24 years old, was admitted for inpatient treatment at GBU RO PTKD for infiltrative tuberculosis S1-2 of the right lung MBT (+) IA, iv.

The condition of the patient upon admission is satisfactory, he does not actively complain, the skin is pale, the nutrition is low, the temperature is normal. Auscultatory: in the lungs against the background of vesicular breathing in the upper sections on the right, single, unstable dry rales. Respiratory rate (BH) - 19 in 1 minute, blood pressure (BP) - 120/85 mm Hg, pulse rate (PE) - 72 in 1 minute.

Survey data at admission:

Spiral computed tomography of the chest organs - on the right in S1-2 are multiple polymorphic foci of a confluent character, a heterogeneous structure due to small areas of destruction.

Blood test: hemoglobin - 145 g / l, red blood cells - 5.3 × 10 ¹² / l, white blood cells - 6.1 × 10 ⁹ / l, eosinophils - 1%, stab neutrophils - 6%, segmented neutrophils - 60%, lymphocytes - 25%, monocytes - 8%, ESR - 12 mm / hour.

Sputum smear analysis by direct bacterioscopy - acid-resistant mycobacteria (CMC) 1-2 in the field of view.

Sputum culture on Wednesday Levenshtein-Jensen - up to 10 CFU.

WASTES MGIT sputum test - a positive result on the office.

PCR is a positive result on the Office.

Mantoux test with 2 tuberculin units (TE) - 17 mm.

Test with Diaskintest - 12 mm.

Biochemical blood test: AlAT - 32.0 IU / ml, AsAT - 27.7 IU / ml, total bilirubin - 7.2 μmol / L.

Immunogram - CD4 + lymphocytes - 30.6%, CD8 + lymphocytes - 34.2%, CD20 + lymphocytes - 14.2%, CD16 + lymphocytes - 7.4%, CD25 + lymphocytes - 10.0%, immunoregulatory index - 0.89.

Indicators of free radical oxidation: plasma catalase - 52.24 μmol Н ₂ О ₂ / min × l, erythrocyte catalase - 68.63 μmol Н ₂ О ₂ / min × mgНв, superoxide dismutase in erythrocytes - 4.02 cu / mgNv, myeloperoxidase - 2.34 cu / mg / min, chemiluminescence of blood plasma - 4672.12 pulse / 6 sec.

On the basis of the examination data, patient A. was diagnosed with the diagnosis: infiltrative tuberculosis S1-2 of the right lung in the phase of infiltration and decay of the office (+) IA, iv.

Patient A. was treated according to the claimed method: a course of anti-tuberculosis therapy was prescribed and carried out in accordance with the standard I regimen: streptomycin 1 g / m, isoniazid - 0.6 g, rifampicin 0.6 g, pyrazinamide 1.5 g, Karsil 35 mg 3 times a day, vitamin B6 10 mg orally. From the first day of treatment, patient A. was orally administered Wobenzym for 60 days daily, 1 tablet 2 times a day 30 minutes before meals. Additionally, from the first day, 10 infusions of Reamberin were included in the course of treatment, which were administered to the patient once a day every other day intravenously in a dose of 400 ml per infusion. After 60 days from the start of treatment, Wobenzym was canceled, and patient A. underwent a control examination.

Control Examination Data:

Spiral computed tomography - in S1-2 of the right lung, significant resorption of focal-infiltrative changes, closure of destruction sites.

Blood test: hemoglobin - 150 g / l, red blood cells - 5.1 × 10 ¹² / l, white blood cells - 5.4 × 10 ⁹ / l, eosinophils - 1%, stab neutrophils - 3%, segmented neutrophils - 59%, lymphocytes - 29%, monocytes - 8%, ESR - 5 mm / hour.

The study of sputum smear by bacterioscopy - CMC not found.

The results of sputum culture on Wednesday Levenshtein-Jensen - growth of culture of the Office is not.

Sputum examination using the BACTECMGIT method is a negative result on the office.

PCR is a negative result on the Office.

Mantoux test with 2 TE - 8 mm.

Test with Diaskintest - 5 mm.

Biochemical blood test: AlAT - 34.5 IU / ml, AsAT - 24.2 IU / ml, total bilirubin - 5.8 μmol / L.

Immunogram - CD4 + lymphocytes - 49.7%, CD8 + lymphocytes - 24.2%, CD20 + lymphocytes - 11.4%, CD16 + lymphocytes - 9.7%, CD25 + lymphocytes - 16.0%, immunoregulatory index - 2.05.

Indicators of free radical oxidation: plasma catalase - 34.56 μmol H ₂ O ₂ / min × l, erythrocyte catalase - 112.44 μmol H ₂ O ₂ / min × mgHv, superoxide dismutase in red blood cells - 11.27 cu / mgNv, myeloperoxidase - 1.76 cu / mg / min, chemiluminescence of blood plasma - 3612.78 pulse / 6 sec.

Thus, positive dynamics were achieved. Patient A.’s condition improved, infiltrative changes partially resolved, destruction sites were closed, abacillation was achieved, indicators of immune status returned to normal, indicators of free-radical oxidation and antioxidant defense improved.

Further treatment was carried out in accordance with the standard I regimen: isoniazid - 0.6 g, ethambutol - 1.2 g, rifampicin 0.6 g, pyrazinamide 1.5 g, carlsil 35 mg 3 times a day, vitamin B6 10 mg orally .

After 3 months from the start of treatment, patient A. with positive clinical and radiological dynamics was discharged to continue treatment on an outpatient basis. During treatment, there were no adverse hepatotoxic reactions to anti-TB drugs.

Example 2: patient Y., 31 years old, was admitted for inpatient treatment at the State Public Institution “PTKD” for infiltrative tuberculosis of the upper lobe of the left lung in the phase of infiltration, decay, and seeding of the office (+) IA, iv.

The patient's condition at admission is moderate, complaints of periodic dry cough, pale skin, nutrition is low, the temperature is raised to 37.2 ° C. Auscultatory: in the lungs one can hear respiration vesicular with a hard tinge, intermittent dry rales in the upper lobe of the left lung. Respiratory rate (BH) - 21 in 1 minute, blood pressure (BP) - 100/70 mm Hg, pulse rate (PE) - 74 in 1 minute.

Survey data at admission:

Spiral computed tomography - in the upper lobe of the left lung there are multiple polymorphic foci of drainage character, with small areas of destruction, in S6 on the left - single foci of screening.

Blood test: hemoglobin - 135 g / l, red blood cells - 4.1 × 10 ¹² / l, white blood cells - 7.1 × 10 ⁹ / l, eosinophils - 1%, stab neutrophils - 8%, segmented neutrophils - 64%, lymphocytes - 23%, monocytes - 4%, ESR - 19 mm / hour.

Sputum smear analysis by direct bacterioscopy - KUM 1-2 in the field of view.

Sputum culture on Wednesday Levenshtein-Jensen gave growth of 2 CFU.

WASTES MGIT sputum test - a positive result on the office.

PCR is a positive result on the Office.

Mantoux test with 2 TE - 17 mm.

Test with Diaskintest - 12 mm.

Biochemical blood test: AlAT - 38.4 IU / ml, AsAT - 29.2 IU / ml, total bilirubin - 13.3 μmol / L.

Immunogram - CD4 + lymphocytes - 32.8%, CD8 + lymphocytes - 35.9%, CD20 + lymphocytes - 18.4%, CD16 + lymphocytes - 8.0%, CD25 + lymphocytes - 12.2%, immunoregulatory index - 0.91.

Indicators of free radical oxidation: plasma catalase - 51.90 μmol H ₂ O ₂ / min × l, erythrocyte catalase - 62.29 μmol H ₂ O ₂ / min × mgHv, superoxide dismutase in red blood cells - 3.86 cu / mgNv, myeloperoxidase - 2.65 cu / mg / min, chemiluminescence of blood plasma - 4859.30 pulses / 6 sec.

Based on the examination data, patient Y was confirmed with a preliminary diagnosis: infiltrative tuberculosis of the upper lobe of the left lung in the phase of infiltration, decay, and seeding of the office (+) IA, iv.

Patient Yu was treated according to the claimed method: a course of anti-tuberculosis therapy was prescribed and carried out in accordance with the standard I regimen: streptomycin 1 g / m, isoniazid - 0.6 g, rifampicin 0.6 g, pyrazinamide 1.5 g, Karsil 35 mg 3 times a day, vitamin B6 10 mg orally. From the first day of treatment, patient Yu was orally administered Wobenzym for 60 days daily, 1 tablet 2 times a day 30 minutes before meals. Additionally, from the first day, 10 infusions of Reamberin were included in the course of treatment, which were administered to the patient once a day every other day intravenously in a dose of 400 ml per infusion. After 60 days from the start of treatment, Wobenzym was canceled, and a control examination was conducted for patient Yu.

Control Examination Data:

Spiral computed tomography - in the upper lobe and S6 of the left lung, significant resorption of focal-infiltrative changes, a decrease in the number of foci, and closure of destruction sites.

Blood test: hemoglobin - 144 g / l, red blood cells - 4.9 × 10 ¹² / l, white blood cells - 6.2 × 10 ⁹ / l, eosinophils - 1%, stab neutrophils - 3%, segmented neutrophils - 56%, lymphocytes - 29%, monocytes - 11%, ESR - 4 mm / hour.

Sputum smear analysis by bacterioscopy - no CMC found.

Two sputum cultures on Wednesday Levenshtein-Jensen - there is no growth of culture of the Office.

WASTES MGIT sputum test - negative for MBT.

PCR is a negative result on the Office.

Mantoux test with 2 TE - 11 mm.

Test with Diaskintest - 10 mm.

Biochemical blood test: AlAT - 33.8 IU / ml, AcAT - 26.4 IU / ml, total bilirubin - 9.1 μmol / L.

Immunogram - CD4 + lymphocytes - 48.6%, CD8 + lymphocytes - 26.9%, CD20 + lymphocytes - 11.7%, CD16 + lymphocytes - 8.1%, CD25 + lymphocytes - 15.5%, immunoregulatory index - 1.8.

Indicators of free radical oxidation: plasma catalase - 37.67 μmol H ₂ O ₂ / min × l, erythrocyte catalase - 134.28 μmol H ₂ O ₂ / min × mgHv, superoxide dismutase in erythrocytes - 12.12 cu / mgNv, myeloperoxidase - 1.60 cu / mg / min, chemiluminescence of blood plasma - 4128.48 imp./6 sec.

Thus, positive dynamics were achieved. Patient Yu’s condition improved, infiltration resolved significantly, the number and size of foci decreased, destruction sites closed, abacillation was achieved, immune status indicators returned to normal, free radical oxidation and antioxidant defense improved.

Further treatment was carried out in accordance with the standard I regimen: isoniazid - 0.6 g, ethambutol - 1.2 g, rifampicin 0.6 g, pyrazinamide 1.5 g, carlsil 35 mg 3 times a day, vitamin B6 10 mg orally .

After 3 months from the start of treatment, patient Y. with positive clinical and radiological dynamics was discharged to continue treatment on an outpatient basis. During treatment, there were no adverse hepatotoxic reactions to anti-TB drugs.

Under our supervision were 20 patients with pulmonary tuberculosis who received treatment according to the claimed method. To compare the effectiveness of the proposed method for the treatment of patients with pulmonary tuberculosis, a retrospective analysis of 20 case histories of patients previously treated according to the prototype was performed. The groups formed were homogeneous by gender, age, prevalence of tuberculous changes in the lungs, the presence of decay, and bacterial excretion.

The dynamics of resorption of infiltration, closure of decay cavities, abacillation was evaluated after 60 days from the start of treatment (see table). In patients of the main group who took treatment according to the claimed method, the effectiveness of treatment was significantly higher than in patients of the comparison group who received treatment according to the prototype: in terms of resorption of infiltration - 1.36 times, closure of decay cavities - 1.5 times, abacillation - 2.0 times.

When assessing the incidence of adverse hepatotoxic reactions, a clear advantage of the proposed method of treatment was revealed. In patients of the main group who received treatment according to the claimed method, the occurrence of adverse hepatotoxic reactions to anti-TB drugs was not observed, while in the comparison group treated according to the prototype, 5 patients (25.0%) showed hepatoxic reactions.

Thus, the claimed method of treatment of patients with pulmonary tuberculosis can significantly increase the effectiveness of treatment: to reduce the time of resorption of infiltration, closing the cavity of decay and abacillation, to reduce the incidence of adverse hepatotoxic reactions.

Claims (1)

A method of treating patients with pulmonary tuberculosis, which provides for antibiotic therapy according to standard regimens with the introduction of Wobenzym orally daily 1 tablet 30 minutes before meals to the patient, characterized in that the course of treatment from the first day additionally includes 10 infusions of Reamberin, which are administered to the patient once a day every other day intravenously in a dose of 400 ml per infusion, and Wobenzym is administered to the patient 2 times a day for 60 days.