Method of treating tuberculosis with multiple drug resistance

FIELD: medicine.

SUBSTANCE: invention refers to a method of treating tuberculosis with multiple drug resistance characterised by prescribing a combination of six anti-tuberculosis preparations in the intensive phase of chemotherapy and five preparations - in the phase of the 20-month therapy continuation, wherein the intensive phase duration makes at least 8 months until obtaining four negative culture results every month in tuberculosis with multiple drug resistance and until obtaining two negative culture results in all other cases of tuberculosis with multiple drug resistance, the phase of the therapy continuation makes 12 months.

EFFECT: higher clinical effectiveness.

1 tbl, 9 ex

 

The invention relates to the field of medicine and relates to a method of treatment of multidrug resistant TB (MDR TB). The Russian Federation is among the countries with high burden of tuberculosis, despite the stabilization of the main epidemiological indicators in the first years of the new century. The incidence of tuberculosis in 2010 amounted to 77.4 per 100 thousand population and death rate of 15.4 per 100 thousand population. However, the efficiency of treatment of TB patients is not high enough.

The reason for this is the huge reservoir of tuberculosis infection multi-drug resistance (MDR TB). In 2009, worldwide there were about 30,000 cases of MDR-TB.

Drug resistance of Mycobacterium tuberculosis (DR office) is one of the major factors limiting the effectiveness of chemotherapy (XT) tuberculosis and is inherently the property of the office to adapt to different environmental conditions, including to develop resistance to anti-TB drugs [Ore N. M. Drug resistance of Mycobacterium tuberculosis. - M., 1969. - 287 p.].

The concept of drug resistance of Mycobacterium tuberculosis occurred soon after the opening of the first anti-TB drugs. Therapy one, effective in early stages chemotherapy drug n�minueto led to the development of resistance of mycobacteria to him. The problem was solved by assigning patients to two or more drugs simultaneously. The first chemotherapy regimens appeared in the 50s, following the opening of the first of streptomycin, and later the PAS and isoniazid, but were soon discovered the MBT strains that are resistant to these drugs. Combined treatment prevented the development of resistance and resulted in increased cure rates. After the discovery of rifampicin in 1966, the British medical research Council and other organizations conducted a series of clinical trials assessing the efficacy of various combinations of anti-TB drugs (SLD) of the main series. Studies have shown 97% effectiveness of chemotherapy regimens including isoniazid and rifampicin, with their short-term use over 6 months [Bastian I., Portal F. multidrug resistant. - M.: Medicine and life, 2003. - 368 p.]. Therapy with multiple, 4-6 drugs at the same time, became a fundamental principle for the treatment of tuberculosis [Yerokhin, V. V. Diagnosis and treatment of multidrug resistant pathogen. - M., 2012].

However, persons already identified with MDR-TB cannot be treated with standard short-course chemotherapy [Farmer P, Kim JY. / Community-based approaches to the control of multidrug - resistant tuberculosis: introducing DOTS-PLUS. Br Med J 1998; 31: 671-674]. A cure rate of MDR-TB patients, who was treated by chemotherapy regimens for patients who have been previously treated for TB (3 months - isoniazid, rifampicin, ethambutol, pyrazinamide, streptomycin, 1 month of isoniazid, rifampicin, ethambutol, pyrazinamide and 5 months of isoniazid, rifampicin, ethambutol), in various TB programs was 0-36% [Lan NTN, lademarco MF, Binkin NJ, Tung LB, Quy HT, Cj NV. / A case series: initial outcome of persons with multidrug-resistant tuberculosis after treatment with the WHO standard re-treatment regimen in Ho Chi Minh City, Vietnam. Int J Tuberc Lung Dis: 2001; 5:575-8].

Currently, the treatment of MDR TB requires a large amount of time, up to 24 months. It runs using 5 second-line drugs, greatly inferior in its activity drugs the main series and exceeding their toxicity [Khomenko A. G. Tuberculosis. CH.9. The treatment of tuberculosis, Moscow, Medicine, 1996; guidelines for the treatment of multidrug resistance. Partners in the name of health, 2003].

Clofazimine was previously registered for use for the treatment of leprosy, however, also been shown that this drug possesses anti-TB activity, including against some strains of multidrug resistant [guidelines for the programmatic management of drug-resistant tube�of tuberculosis. Who, Geneva, 2007, 217 p.].

Clofazimine - riminophenazine derived. Clofazimine inhibits replication and growth, selective binding with guanine in DNA of mycobacteria. In vitro clofazimine has bactericidal activity against M. tuberculosis and only bacteriostatic against other mycobacteria. IPC clofazimine lies in the range from 0.06 to 2.0 µg/ml in the study on N on WASTES.

The situation is greatly complicated by the emergence of the most dangerous varieties of MDR-TB - TB extensively drug-resistant (XDR-TB) at which resistance to isoniazid and rifampicin joins the resistance of mycobacteria to fluoroquinolones and to one of the aminoglycoside or polypeptide. In 2009, nearly 60 countries have noted the emergence of XDR-TB, including the Russian Federation.

Known methods of treatment of multidrug resistance using a combination of different anti-TB drugs with clofazimine. The most effective method of treatment requires a minimum of 9 months of treatment with Gatifloxacin, clofazimine, ethambutol and pyrazinamide during the entire treatment period, with the addition of protionamide, kanamycin, and high-dose isoniazid in the intensive phase for at least 4 months [Am J Respir Crit Care Med, 2010 Sep 1; 182(5):684-92. Epub 2010 May 4. "Short, highly effective and inexpensive standardized treatment of multidrugresistant tuberculosis. Van Deun A, Maug AK, Salim MA, Das PK, Sarker MR, Dam P, Rieder HL]. In General, due to the low efficiency of backup combinations of medicines and high risk of recurrence caused by Mycobacterium tuberculosis with multiple drug resistance, drug therapy is not less than 18 to 22 months [Khomenko A. G. Tuberculosis. CH.9. The treatment of tuberculosis. - M., Medicine, 1996; guidelines for the treatment of multidrug resistance. Partners in the name of health, 2003].

Thus, as we have seen above, the problem of expanding Arsenal of means for treatment of multidrug resistance remains a crucial one.

In accordance with the invention describes a method for the treatment of tuberculosis with multiple drug resistance with chemotherapy, characterized by the fact that the prescribed combination of six anti-TB drugs during the intensive phase of chemotherapy and five anti-TB drugs in the continuation phase of treatment for 20 months, where the duration of the intensive phase is at least 8 months before receiving four negative sowings at intervals of one month in tuberculosis with extensive drug resistance and to obtain two negative crops in other cases of multidrug-generic�'s internal resistance and the duration of the continuation phase of treatment is 12 months, in this case in the intensive phase of treatment prescribed amikacin or capreomycin depending on the sensitivity of Mycobacterium tuberculosis in an amount of 1.0 g daily 1 time per day intramuscularly, when the resistance of Mycobacterium tuberculosis to kanamycin/amikacin prescribe capreomycin 1.0 g/day, when the resistance of Mycobacterium tuberculosis to capreomycin, but maintaining the sensitivity of Mycobacterium tuberculosis to kanamycin or amikacin prescribe kanamycin 1.0 g/day or amikacin 1.0 g/day, when the resistance of Mycobacterium tuberculosis to capreomycin and amikacin/kanamycin administered capreomycin 1.0 g/day, with sensitivity to amikacin prescribe kanamycin 1.0 g/day;

levofloxacin 0.75 g while maintaining the sensitivity of Mycobacterium tuberculosis to ofloxacin, levofloxacin 1.0 g or moxifloxacin 0.4 g in resistance of Mycobacterium tuberculosis to ofloxacin oral daily 1 time per day, with sensitivity to levofloxacin 0.75 g/day administered ofloxacin 0.8 g/day, with sensitivity to levofloxacin 1.0 g/day administered moxifloxacin 0.4 g/day, with intolerance moxifloxacin 0.4 g/day administered levofloxacin 1.0 g/day;

clofazimine 0.3 g orally daily 1 time per day during the first 4-6 weeks with gradual reduction of the dose to 0.2 g/day;

pyrazinamide 1.5-2.0 g/day oral e�dnevno 1 time per day;

terizidone 0.5-0.75 g/day oral daily 2 times a day or cycloserine 0.75 g/day oral daily 2-3 times a day when poor tolerability of terizidone, with intolerance of cycloserine and terizidone prescribe protionamid 0.75 g/day oral daily 2-3 times a day when saving to him of drug susceptibility of Mycobacterium tuberculosis; and

ethambutol is 1.2-1.6 g/day oral daily 1 time per day or paraaminosalicylic acid of 8.0-12.0 g/day or protionamid 0.75 g/day, while maintaining sensitivity to him of Mycobacterium tuberculosis daily 2-3 times per day, while maintaining the sensitivity of Mycobacterium tuberculosis to ethambutol prescribe ethambutol resistance in Mycobacterium tuberculosis to ethambutol or intolerance prescribed paraaminosalicylic acid of 8.0-12.0 g/day, with intolerance paraaminosalicylic acid and maintaining the drug sensitivity of Mycobacterium tuberculosis to protionamide prescribe protionamid 0.75 g/day oral daily 2-3 times a day,

and in the continuation phase of treatment prescribed:

levofloxacin 0.75 g/day while maintaining the sensitivity of Mycobacterium tuberculosis to ofloxacin, levofloxacin 1.0 g/day or moxifloxacin 0.4 g/day in resistance of Mycobacterium tuberculosis to ofloxacin per os daily 1 time per day, PR� intolerance levofloxacin 0.75 g/day administered ofloxacin 0.8 g/day, in rejecting levofloxacin 1.0 g/day administered moxifloxacin 0.4 g/day, with intolerance moxifloxacin 0.4 g/day administered levofloxacin 1.0 g/day;

clofazimine 0.2 g/day oral daily 1 time per day;

pyrazinamide 1.5-2.0 g/day oral daily 1 time per day;

terizidone 0.5-0.75 g/day oral daily 2 times a day or cycloserine 0.75 g/day oral daily 2-3 times a day when poor tolerability of terizidone, with intolerance of cycloserine and terizidone prescribe protionamid 0.75 g/day oral daily 2-3 times a day when saving to him of drug susceptibility of Mycobacterium tuberculosis; and

ethambutol is 1.2-1.6 g/day oral daily 1 time per day or paraaminosalicylic acid of 8.0-12.0 g/day or protionamid 0.75 g/day, while maintaining sensitivity to him of Mycobacterium tuberculosis daily 2-3 times per day, while maintaining the sensitivity of Mycobacterium tuberculosis to ethambutol prescribe ethambutol resistance in Mycobacterium tuberculosis to ethambutol or intolerance prescribed paraaminosalicylic acid of 8.0-12.0 g/day, with intolerance paraaminosalicylic acid and maintaining the drug sensitivity of Mycobacterium tuberculosis to protionamide prescribe protionamid 0.75 g/day oral daily 2-3 times a day.

In the intensive phase of treatment prescribed:

1. Amikacin or capreomycin depending on the sensitivity of the Ofce of 1.0 g daily 1 time per day intramuscularly. When resistance to kanamycin/amikacin is assigned capreomycin 1.0 g/day. When resistance to capreomycin, but keeping MBT sensitivity to kanamycin or amikacin, assigned kanamycin 1.0 g/day or amikacin 1.0 g/day. When resistance to capreomycin and amikacin/kanamycin is assigned capreomycin 1.0 g/day. In the untreated amikacin assigned kanamycin 1.0 g/day.

2. Levofloxacin 0.75 g when the saved MBT sensitivity to ofloxacin, levofloxacin 1.0 g or moxifloxacin 0.4 g with resistance to ofloxacin oral daily 1 time per day. In rejecting levofloxacin 0.75 g/day is assigned ofloxacin 0.8 g/day. In rejecting levofloxacin 1.0 g/day is assigned moxifloxacin 0.4 g/day. In case of intolerance moxifloxacin 0.4 g/day is assigned levofloxacin 1.0 g/day.

3. Clofazimine 0.3 g orally daily 1 time per day during the first 4-6 weeks with gradual reduction of the dose to 0.2 g/day.

4. Pyrazinamide 1.5-2.0 g/day oral daily 1 time per day.

5. Terizidone 0.5-0.75 g/day oral daily 2 times a day. Terizidone can be replaced by cycloserine 0.75 g/day oral daily 2-3 times a day when bad� tolerability of the drug to patients. In rejecting cycloserine and terizidone assigned protionamid 0.75 g/day oral daily 2-3 times a day when saving to him the office of drug sensitivity.

6. Ethambutol is 1.2-1.6 g/day oral daily 1 time per day or PASK 8,0-12,0 g/day, or protionamid 0.75 g/day, while maintaining sensitivity to him the office every day 2-3 times a day. While maintaining the sensitivity of the office assigned to ethambutol and ethambutol. With resistance to ethambutol or intolerances assigned PASK 8,0-12,0 g/day. In rejecting PASK and conservation of medicinal MBT sensitivity to protionamide assigned protionamid 0.75 g/day oral daily 2-3 times a day.

And in the continuation phase of treatment prescribed:

1. Levofloxacin 0.75 g/day when stored MBT sensitivity to ofloxacin, levofloxacin 1.0 g/day or moxifloxacin 0.4 g/day with resistance to ofloxacin per os daily 1 time per day. In rejecting levofloxacin 0.75 g/day is assigned ofloxacin 0.8 g/day. In rejecting levofloxacin 1.0 g/day is assigned moxifloxacin 0.4 g/day. In case of intolerance moxifloxacin 0.4 g/day is assigned levofloxacin 1.0 g/day.

2. Clofazimine 0,2 oral daily 1 time per day.

3. Pyrazinamide 1.5-2.0 g/day oral daily 1 time per day.

4. Terizidone 0.5-0.75 g/day oral daily 2 p�for a day. Terizidone can be replaced by cycloserine 0.75 g/day oral daily 2-3 times a day when poor tolerability of the drug in patients. In rejecting cycloserine and terizidone assigned protionamid 0.75 g/day oral daily 2-3 times a day when saving to him the office of drug sensitivity.

5. Ethambutol is 1.2-1.6 g/day oral daily 1 time per day or paraaminosalicylic acid (PAS) 8,0-12,0 g/day or protionamid 0.75 g/day, while maintaining sensitivity to him the office every day 2-3 times a day. While maintaining the sensitivity of the office assigned to ethambutol and ethambutol. With resistance to ethambutol or intolerances assigned PASK 8,0-12,0 g/day. In rejecting PASK and conservation of medicinal MBT sensitivity to protionamide assigned protionamid 0.75 g/day oral daily 2-3 times a day.

The use of this regimen in these ratios significantly increases the effectiveness of treatment by increasing the antimicrobial activity against the drug-sensitive Mycobacterium tuberculosis.

Biological studies in vivo were conducted in order to examine the specific activity against M. tuberculosis H37Rv (ILO) announced a new dosing regimen (combination of drugs), showed that the claimed combination of drugs they�em high antituberculosis activity.

The justification of the scheme and an explanation of the choice of drugs

In accordance with international guidelines for management of Dr-TB in 2011 [Guidelines for the programmatic management of drug-resistant tuberculosis - 2011 update], [Guidelines for the programmatic management of drug-resistant tuberculosis - 2008 update] in the mode of treatment of MDR-TB must be included aminoglycosides (amikacin/kanamycin) or polypeptide (capreomycin), fluoroquinolone (levofloxacin), pyrazinamide, cycloserine and ethionamide/protionamide. If it is impossible to assign cycloserine assigned PASK. Based on this scheme, but given the high prevalence LOU office in Russia to thioamides (ethionamide/protionamide), the scheme is slightly modified and included in the scheme PASK.

The rationale for each drug schemes

The aminoglycoside and polypeptide have bactericidal activity against MBT, there are many data supporting the need for their use. Drugs in this group are a key component of the treatment regimen of MDR-TB. Injectable drugs administered in a hierarchical order, based on their effectiveness, side effects and cost. In the case of MBT sensitivity to kanamycin choose kanamycin. If the selected patient ILO resistant to kanamycin should be used capreomycin. If the selected patient ILO resistant to Km, Cm, you should explore Leka�governmental sensitivity to Am. In patients with renal insufficiency, hearing loss should be borne in mind the possibility of using capreomycin. Although the side effects of capreomycin similar to side effects of aminoglycosides, they develop, according to available data, much less.

Fluoroquinolones are the only oral second-line drugs with bactericidal action. They should be incorporated in the treatment of patients with MDR-TB whenever possible. Drugs fluoroquinolone demonstrate high antibacterial activity against Mycobacterium in in vitro and in vivo. High bioavailability in oral administration, good overall tolerability and relatively low cost make fluoroquinolones indispensable second-line drug for the treatment of drug-resistant tuberculosis. Levofloxacin is more active than ofloxacin against sensitive to ofloxacin MBT strains, and is also effective against 50% of strains resistant to ofloxacin. Moxifloxacin has the highest bactericidal activity and lowest MICK [Migliori GB, Lange C, Girardi E, et al. Fluoroquinolones: are they essential to treat multidrug-resistant tuberculosis// Eur Respir J. - 2008. - No. 31. - R. 904-10].

Pyrazinamide is a drug primary series with a unique property - activity in an acidic environment, according to the who guidelines, it is recommended to include in the mode hamiota�Apia MDR-TB always [Y. Zhang, Mitchison D. The curious characteristics of pyrazinamide: a review// hit J Tuberc Lung Dis. - 2003. - №7(1). - P. 6-21].

Ethambutol is a first - line therapy, should be used always, when it saved the drug sensitivity because it is more effective and better tolerated by patients than bakteriostaticheskie drugs drugs second (backup) of a number.

Thioamide, cycloserine and PAS are used in the treatment of patients with MDR-TB, however, are primarily bacteriostatic. Tolerability of these drugs is not as good as the first-line drugs and fluoroquinolones. The inclusion of these drugs in the treatment regimens for MDR-TB must be based on data on the spectrum of available drug resistance and tolerability.

Ethionamide (protionamid) is the most widely available drugs in this group, but due to long and continuous use of it in Russia in the treatment of patients with drug-resistant tuberculosis drug resistance to thioamides is the highest of this group of drugs.

Cycloserine - TB drug whose efficacy has been; however, it causes neuropsychiatric side effects, which, although treatable, however, require careful observation. It is therefore advisable to replace terizidone. Terizidone contains in its SOS�Ave two molecules of cycloserine, has the same efficacy but better tolerability and can be used instead.

Paraaminosalicylic acid (PAS) is an effective bacteriostatic antituberculosis agent. After its discovery and use in the composition of the regimen: isoniazid, streptomycin, PAS, in the 60 years, the drug has shown its effectiveness. In the past 30 years, since the discovery of rifampicin, it has not been used in the treatment of tuberculosis in the Russian Federation, and according to microbiologists, to him did not develop drug resistance.

The use of the inventive regimen increases the efficiency of treatment of patients with MDR/XDR-TB.

Biological studies in vivo showed that the proposed scheme has high anti-TB activity and provides the most complete recovery of structural and functional features of the lungs and other parenchymal organs.

When conducting experimental studies to determine this activity identified the following indicators:

- the average life span after infection with a lethal dose of Mycobacterium in different experimental groups;

- assessment of microbiological assay of bactericidal and bacteriostatic activity of the test combinations.

Cultural method of the study to determine anti-TB activity of� in the system in vivo carried out on mice of the line C57BL/6. In the experience were included mice that have passed the quarantine. The mice weight 22-25 g. Infection was performed by a two-week culture of M. tuberculosis H37 RV by intravenous injection in the lateral tail vein at a dose of 5×106CFU/mouse. For the preparation of suspensions of M. tuberculosis aliquot of the biological material was diluted in phosphate buffer solution to a concentration of 5×106CFU/mouse.

All experimental animals were divided into groups of 45 animals in each treatment group. Treatment of animals was started 14 days after infection, in the lungs when we detected multiple foci of tuberculosis infection.

Chemotherapy was performed daily, the drugs were administered orally according to the proposed treatment schemes, in the form of solutions pre-ground powders of 0.5 ml/mouse.

According to the program of studies were conducted in the intensive phase and part of the continuation phase of treatment. Evaluation of the results of the proposed schemes was carried out in several stages: evaluated the effectiveness of therapy, the intensive phase of treatment and the efficacy of therapy during the continuation phase of treatment. In turn, the efficiency and the intensive phase and the continuation phase of treatment were assessed at certain intervals. Intensive phase: point 1 - 14 days after infection, point 2 - after 2 months on�Ala treatment point 3 - 4 months after the start of treatment, period 4 - 5 months after the start of treatment, period 5 - 6 months after the start of treatment, period of 6 - 7 months after the start of treatment, period 7 - 8 months after the start of treatment. The continuation phase of treatment: point 1 - 2 months after the start of treatment in this phase, period 2 - 5 months after the start of treatment in this phase. At each valuation period was used in 5 animals of each experimental group. To determine the effectiveness of therapy is a necessary part of the experimental animals were withdrawn from the experiment by cervical dislocation to determine the number of colony forming units (CFU) of M. tuberculosis in the lungs of mice, and histological examination of the tissues of the lung, liver and spleen.

To determine the number of bacteria (CFU MBT) in the lungs of infected mice analyzed material was treated with 10% solution of sodium phosphate, homogenized in 2 ml of saline, then prepared a series of 10-fold dilutions of the initial suspension in physiological solution and 50 µl of each dilution was placed on a Petri dish with löwenstein-Jensen medium. Petri dishes were incubated at 37°C for 42 days. The original suspension was stored at 4°C. the Crops reviewed every 7 days. At the end of the time of cultivation ol�plagued counting microcolony. The concentration of bacteria in suspension is expressed by the number of colony forming units per milliliter (CFU/ml). Grading of assessment was carried out in accordance with "guidance on the use of standardized microbiological methods of research in tuberculosis".

The animals were divided into following groups:

Group 1. Infected mice without treatment (control)

Group 2. Infected mice receiving a standard treatment regimen as recommended for the standard of care (no clofazimine)

Intensive phase:

Amikacin intramuscularly 1 time per day in the dose of 10 mg/kg daily (3 months)

Levofloxacin orally 1 time a day at a dose of 12.5 mg/kg daily (6 months)

Pyrazinamide orally 1 time a day at a dose of 25 mg/kg daily (6 months)

Protionamid orally 2 times a day in a dose of 15 mg/kg daily (6 months)

Cycloserine oral 2 times a day in a dose of 10 mg/kg daily

Ethambutol orally 1 time a day at a dose of 25 mg/kg daily

The continuation phase of treatment:

Levofloxacin orally 1 time a day at a dose of 12.5 mg/kg daily (6 months)

Pyrazinamide orally 1 time a day at a dose of 25 mg/kg daily (6 months)

Protionamid orally 2 times a day in a dose of 15 mg/kg daily (6 months)

Cycloserine oral 2 times a day in a dose of 10 mg/kg daily

Ethambutol orally 1 time a day at a dose of 25 mg/kg daily

�Rupp 3. Infected mice receiving the investigational treatment regimen with clofazimine

Intensive phase:

Amikacin intramuscularly 1 time a day at a dose of 16 mg/kg daily

Levofloxacin orally 1 time a day at a dose of 12.5 mg/kg daily

Clofazimine orally 1 time a day at a dose of 5 mg/kg during the first 4 weeks with gradual reduction of the dose to 3.3 mg/kg.

Pyrazinamide orally 1 time a day at a dose of 28 mg/kg daily

Terizidone orally 2 times a day in a dose of 10 mg/kg daily

Ethambutol orally 1 time a day at a dose of 25 mg/kg daily

The continuation phase of treatment:

Levofloxacin orally 1 time a day at a dose of 12.5 mg/kg daily

Clofazimine orally 1 time a day at a dose of 3.3 mg/kg

Pyrazinamide orally 1 time a day at a dose of 28 mg/kg daily

Terizidone orally 2 times a day in a dose of 10 mg/kg daily

Ethambutol orally 1 time a day at a dose of 25 mg/kg daily

Group 4. Infected mice receiving the investigational treatment regimen with clofazimine

Intensive phase:

Capreomycin given intramuscularly 1 time a day at a dose of 16 mg/kg daily

Levofloxacin orally 1 time a day at a dose of 12.5 mg/kg daily

Clofazimine orally 1 time a day at a dose of 5 mg/kg during the first 4 weeks with gradual reduction of the dose to 3.3 mg/kg.

Pyrazinamide orally 1 time a day at a dose of 28 mg/kg daily

Terizidone of peror�flax 2 times a day in a dose of 10 mg/kg daily

Ethambutol orally 1 time a day at a dose of 25 mg/kg daily

The continuation phase of treatment:

Levofloxacin orally 1 time a day at a dose of 12.5 mg/kg daily

Clofazimine orally 1 time a day at a dose of 3.3 mg/kg

Pyrazinamide orally 1 time a day at a dose of 28 mg/kg daily

Terizidone orally 2 times a day in a dose of 10 mg/kg daily

Ethambutol orally 1 time a day at a dose of 25 mg/kg daily

Group 5. Infected mice receiving the investigational treatment regimen with clofazimine

Intensive phase:

Amikacin intramuscularly 1 time a day at a dose of 16 mg/kg daily

Levofloxacin orally 1 time a day at a dose of 12.5 mg/kg daily

Clofazimine orally 1 time a day at a dose of 5 mg/kg during the first 4 weeks with gradual reduction of the dose to 3.3 mg/kg.

Pyrazinamide orally 1 time a day at a dose of 28 mg/kg daily

Protionamid orally 2 times a day in a dose of 15 mg/kg daily

Ethambutol orally 1 time a day at a dose of 25 mg/kg daily

The continuation phase of treatment:

Levofloxacin orally 1 time a day at a dose of 12.5 mg/kg daily

Clofazimine orally 1 time a day at a dose of 3.3 mg/kg

Pyrazinamide orally 1 time a day at a dose of 28 mg/kg daily

Protionamid orally 2 times a day in a dose of 15 mg/kg daily

Ethambutol orally 1 time a day at a dose of 25 mg/kg daily

Group 6. Infected �ISI, receiving the investigational treatment regimen with clofazimine

Intensive phase:

Amikacin intramuscularly 1 time a day at a dose of 16 mg/kg daily

Levofloxacin orally 1 time a day at a dose of 12.5 mg/kg daily

Clofazimine orally 1 time a day at a dose of 5 mg/kg during the first 4 weeks with gradual reduction of the dose to 3.3 mg/kg.

Pyrazinamide orally 1 time a day at a dose of 28 mg/kg daily

Terizidone orally 2 times a day in a dose of 10 mg/kg daily

PASK orally 1 time a day at a dose of 150 mg/kg daily

The continuation phase of treatment:

Levofloxacin orally 1 time a day at a dose of 12.5 mg/kg daily

Clofazimine orally 1 time a day at a dose of 3.3 mg/kg

Pyrazinamide orally 1 time a day at a dose of 28 mg/kg daily

Terizidone orally 2 times a day in a dose of 10 mg/kg daily

PASK orally 1 time a day at a dose of 150 mg/kg daily

Group 7. Infected mice receiving the investigational treatment regimen with clofazimine

Intensive phase:

Amikacin intramuscularly 1 time a day at a dose of 16 mg/kg daily

Levofloxacin orally 1 time a day at a dose of 12.5 mg/kg daily

Clofazimine orally 1 time a day at a dose of 5 mg/kg during the first 4 weeks with gradual reduction of the dose to 3.3 mg/kg.

Pyrazinamide orally 1 time a day at a dose of 28 mg/kg daily

Terizidone orally 2 times a day in a dose of 10 mg/�g daily

Protionamid orally 1 time a day at a dose of 15 mg/kg daily

The continuation phase of treatment:

Levofloxacin orally 1 time a day at a dose of 12.5 mg/kg daily

Clofazimine orally 1 time a day at a dose of 3.3 mg/kg

Pyrazinamide orally 1 time a day at a dose of 28 mg/kg daily

Terizidone orally 2 times a day in a dose of 10 mg/kg daily

Protionamid orally 1 time a day at a dose of 15 mg/kg daily

Group 8. Infected mice receiving the investigational treatment regimen with clofazimine

Intensive phase:

Capreomycin given intramuscularly 1 time a day at a dose of 16 mg/kg daily

Levofloxacin orally 1 time a day at a dose of 12.5 mg/kg daily

Clofazimine orally 1 time a day at a dose of 5 mg/kg during the first 4 weeks with gradual reduction of the dose to 3.3 mg/kg

Pyrazinamide orally 1 time a day at a dose of 28 mg/kg daily

Protionamid orally 1 time a day at a dose of 15 mg/kg daily

PASK orally 1 time a day at a dose of 150 mg/kg daily

The continuation phase of treatment:

Levofloxacin orally 1 time a day at a dose of 12.5 mg/kg daily

Clofazimine orally 1 time a day at a dose of 3.3 mg/kg

Pyrazinamide orally 1 time a day at a dose of 28 mg/kg daily

Protionamid orally 1 time a day at a dose of 15 mg/kg daily

PASK orally 1 time a day at a dose of 150 mg/kg daily

Group 9. Infected mice, �holocause investigational treatment regimen with clofazimine

Intensive phase:

Capreomycin given intramuscularly 1 time a day at a dose of 16 mg/kg daily

Levofloxacin orally 1 time a day at a dose of 12.5 mg/kg daily

Clofazimine orally 1 time a day at a dose of 5 mg/kg during the first 4 weeks with gradual reduction of the dose to 3.3 mg/kg.

Pyrazinamide orally 1 time a day at a dose of 28 mg/kg daily

Terizidone orally 2 times a day in a dose of 10 mg/kg daily

PASK orally 1 time a day at a dose of 150 mg/kg daily

The continuation phase of treatment:

Levofloxacin orally 1 time a day at a dose of 12.5 mg/kg daily

Clofazimine orally 1 time a day at a dose of 3.3 mg/kg

Pyrazinamide orally 1 time a day at a dose of 28 mg/kg daily

Terizidone orally 2 times a day in a dose of 10 mg/kg daily

PASK orally 1 time a day at a dose of 150 mg/kg daily

Key indicators of resistance of the animal to tuberculosis are term survival after infection, the ability to control the multiplication of bacilli in the organs (the number of bacteria measured as CFU).

In mice of group 1 (control) average lifespan after infection was 33.9±0.6 day. Mouse groups of subjects (groups 2-9) receiving different treatment regimens, throughout the experiment and at the time of slaughter remained alive. The number of CFU of the office, sown from the lungs of mice of group 2 (hundred�standard treatment regimen), was higher by 1.5-2 times higher than in mice groups of 3-9. In turn, the number of CFU of the office, sown from the lungs of mice treated with different variants of the claimed treatment was about the same, statistically significant difference was not established.

Table 1 presents data on the assessment of CFU (number of AFB) to the infected organ mice in two stages - intensive phase (phase 1) and continuation phase of treatment (phase 2).

Table 1
Experimental groupThe valuation period (period)
Stage 1Stage 2
123456712
1+++--------
2+++++++++-----
3++++++------
4++++++------
5++++++------
6++++++-- ----
7++++++------
8++++++------
9++++++------
-- - there are no results
- - no of smear -
+ - meager smear-positive
++ - moderate smear-positive
+++ - abundant bacter�vydelenie

The macroscopic examination of internal organs of mice, not treated with chemotherapy (group 1), were found distinct signs of tuberculous inflammation (large foci of infection in the lungs).

When administered intravenously, the office develops in mice exudative-necrotic inflammatory process that attacks various parenchymatous organs. Untreated animals die within 1-2 months. By the time of his death in the lungs, liver, spleen observed hyperemia, sludge of red blood cells, in the large and medium blood vessels are detected form of polymorphonuclear leukocytes (LLP local). Around blood vessels are formed cellular infiltrates consisting of mono - and polynuclear. In the terminal period of the process of cellular infiltrates occupy up to 70% histological slice; their composition is determined by the large accumulation of foamy cells (PC), here we concentrate LLP local forming zone of necrosis. In the liver of untreated mice, in addition to exudative reaction, the formation of perivascular infiltrates, established the development of degenerative changes of hepatocytes, particularly those expressed during the terminal stage of inflammation. Cells of the hepatic beams have enlightened vacuolization cytoplasm, often with signs of dextrally. In areas of necrosis are defined LLP local.

The spleen of control group mice depleted if�pocitame, observed proliferation of stromal elements, the formation of a diffuse mononuclear infiltrates, which are defined LLP local.

In all groups of mice treated according to the regimens, has been received well pronounced therapeutic effect. Almost all animals were observed almost complete recovery of structural and functional features of the lungs, liver, spleen. However, in all parenchymatous organs remained plethora, signs of increased permeability of the microvasculature.

The closest to the normal histological structure of parenchymatous organs was observed in animals of groups 3 to 9.

The study of seed in the groups receiving treatment, revealed a significant positive effect of chemotherapy. Moreover, this effect when using the new scheme of treatment was slightly higher than when using standard. The results of microbiological studies parenchymatous organs showed a progressive sterilization of material examined from Mycobacterium tuberculosis.

From the data obtained it can be concluded that the proposed scheme of treatment of MDR/XDR-TB is effective and has a more pronounced therapeutic effect than standard treatment regimen.

A method for the treatment of multidrug - �karstenii resistance with chemotherapy, characterized by the fact that the prescribed combination of six anti-TB drugs during the intensive phase of chemotherapy and five anti-TB drugs in the continuation phase of treatment for 20 months, where the duration of the intensive phase is at least 8 months to receive four negative sowings at intervals of one month in tuberculosis with extensive drug resistance and to obtain two negative crops in other cases of multidrug resistance and the duration of the continuation phase of treatment is 12 months,
in this case in the intensive phase of treatment prescribed amikacin or capreomycin depending on the sensitivity of Mycobacterium tuberculosis in an amount of 1.0 g daily 1 time per day intramuscularly, when the resistance of Mycobacterium tuberculosis to kanamycin/amikacin prescribe capreomycin 1.0 g/day, when the resistance of Mycobacterium tuberculosis to capreomycin, but maintaining the sensitivity of Mycobacterium tuberculosis to kanamycin or amikacin prescribe kanamycin 1.0 g/day or amikacin 1.0 g/day, when the resistance of Mycobacterium tuberculosis to capreomycin and amikacin/kanamycin administered capreomycin 1.0 g/day, with sensitivity to amikacin prescribe kanamycin 1.0 g/day; levofloxacin 0.75 g with preserved sensitivity m�of karakteri tuberculosis to ofloxacin, levofloxacin is 1.0 g or moxifloxacin 0.4 g in resistance of Mycobacterium tuberculosis to ofloxacin oral daily 1 time per day, with sensitivity to levofloxacin 0.75 g/day administered ofloxacin 0.8 g/day, with sensitivity to levofloxacin 1.0 g/day administered moxifloxacin 0.4 g/day, with intolerance moxifloxacin 0.4 g/day administered levofloxacin 1.0 g/day;
clofazimine 0.3 g orally daily 1 time per day during the first 4-6 weeks with gradual reduction of the dose to 0.2 g/day;
pyrazinamide 1.5-2.0 g/day oral daily 1 time per day;
terizidone 0.5-0.75 g/day oral daily 2 times a day or cycloserine 0.75 g/day oral daily 2-3 times a day when poor tolerability of terizidone, with intolerance of cycloserine and terizidone prescribe protionamid 0.75 g/day oral daily 2-3 times a day when saving to him of drug susceptibility of Mycobacterium tuberculosis; and
ethambutol is 1.2-1.6 g/day oral daily 1 time per day or paraaminosalicylic acid of 8.0-12.0 g/day or protionamid 0.75 g/day, while maintaining sensitivity to him of Mycobacterium tuberculosis daily 2-3 times per day, while maintaining the sensitivity of Mycobacterium tuberculosis to ethambutol prescribe ethambutol resistance in Mycobacterium tuberculosis to ethambutol or naperekos�on prescribed paraaminosalicylic acid of 8.0-12.0 g/day, in rejecting paraaminosalicylic acid and maintaining the drug sensitivity of Mycobacterium tuberculosis to protionamide prescribe protionamid 0.75 g/day oral daily 2-3 times a day,
and in the continuation phase of treatment prescribed:
levofloxacin 0.75 g/day while maintaining the sensitivity of Mycobacterium tuberculosis to ofloxacin, levofloxacin 1.0 g/day or moxifloxacin 0.4 g/day in resistance of Mycobacterium tuberculosis to ofloxacin per os daily 1 time per day, with sensitivity to levofloxacin 0.75 g/day administered ofloxacin 0.8 g/day, with sensitivity to levofloxacin 1.0 g/day administered moxifloxacin 0.4 g/day, with intolerance moxifloxacin 0.4 g/day administered levofloxacin 1.0 g/day;
clofazimine 0,2 oral daily 1 time per day;
pyrazinamide 1.5-2.0 g/day oral daily 1 time per day;
terizidone 0.5-0.75 g/day oral daily 2 times a day or cycloserine 0.75 g/day oral daily 2-3 times a day when poor tolerability of terizidone, with intolerance of cycloserine and terizidone prescribe protionamid 0.75 g/day oral daily 2-3 times a day when saving to him of drug susceptibility of Mycobacterium tuberculosis; and
ethambutol is 1.2-1.6 g/day oral daily 1 time per day or paraaminosalicylic acid of 8.0-12.0 g/cuccioli protionamid 0.75 g/day, while maintaining sensitivity to him of Mycobacterium tuberculosis daily 2-3 times a day while maintaining the sensitivity of Mycobacterium tuberculosis to ethambutol prescribe ethambutol resistance in Mycobacterium tuberculosis to ethambutol or intolerance prescribed paraaminosalicylic acid of 8.0-12.0 g/day, with intolerance paraaminosalicylic acid and maintaining the drug sensitivity of Mycobacterium tuberculosis to protionamide prescribe protionamid 0.75 g/day oral daily 2-3 times a day.



 

Same patents:

FIELD: medicine.

SUBSTANCE: invention concerns a simplified capsular form of clofazimine, containing clofazimine, bee wax, soya bean lecithin, butylhydroxy toluene, soya bean oil, gelatine, glycerol, sorbitol, methylparabene, propylparabene, titanium dioxide, brown chocolate and purified water with preserving high efficacy.

EFFECT: simplifying the form.

4 tbl, 3 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to phthisiology, and can be used in treating pulmonary tuberculosis accompanied by tuberculosis intoxication. To this effect, administering anti-tuberculosis preparations is combined with the additional intravenous drop-by-drop administration of Reamberin, Heptral and antitoxic polyvalent antigangrenous serum (AGS) preceded by the administration of heparin 50 units/kg; Reamberin is administered in an amount of 400 ml on the first and second day for 2 hours; Heptral is introduced in an amount of 400 ml from the first to the fifth day; AGS is administered on the third day in an amount of 30 thousand International Units, on the fourth day in an amount of 60 thousand International Units, in case of a destructive process - in an amount of 60 thousand International Units on the fifth day; AGS is administered in normal saline NaCl 400 ml, and the first 1 ml of the solution is administered for 5 minutes, the rest amount - for 1.5-2 hours.

EFFECT: method enables increasing the clinical effectiveness of pulmonary tuberculosis as soon as possible by binding and neutralising microbial exo- and endotoxins by serum antibodies with no side effects and reduced financial expenses.

4 tbl, 3 ex

FIELD: medicine.

SUBSTANCE: means represents a dry extract of leaves and flowers of Gratiola officinalis, obtained by milling the leaves and flowers of Gratiola officinalis, extraction with 96% alcohol on a water bath to boiling and boiling, evaporation, dilution of the evaporated residue first with distilled water, then by the addition of chloroform, cooling to room temperature and centrifuging with the following separation of a water fraction and drying it under specified conditions.

EFFECT: means is non-toxic, has an expressed anti-tuberculosis action.

2 tbl, 2 ex

FIELD: medicine.

SUBSTANCE: agent is presented in the form of a tablet, contains isoniazid and a substance which reduces its toxicity; as the substance which reduces the isoniazid toxicity, it contains thiotriazolin. The isoniazid/thiotriazolin ratio makes 4:1.

EFFECT: combined antituberculous drug ensures reducing toxicity as compared to the known ones and increasing its pharmacological activity.

2 cl, 1 ex, 1 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a chemical compound of formula wherein R=benzyl and to an antituberculous therapeutic agent representing a composition of imidazo[1,2-b][1,2,4,5]tetrazine derivative of formula I, wherein R=benzyl, isopropyl or phenyl and the known antituberculous preparation pyrazinamide with the ingredients in mole ratio 1:1.

EFFECT: there are prepared new antituberculous therapeutic agents.

2 cl, 2 tbl, 6 ex

FIELD: chemistry.

SUBSTANCE: invention relates to organic chemistry and specifically to nitroimidazooxazine derivatives of general formula I, where n equals 1, V and W independently denote H or CH3, and one of X and Y is H and the other is one of the formulae and , where formula IIa includes a single ring labelled at position 3 and position 4 and containing R1 as a substitute, and formula IIb includes a first ring labelled at position 3 and position 4 and containing as substitutes both R2 and a terminal ring, labelled at position 4 and containing R1 as a substitute, where the single ring of formula IIa and the first ring and the terminal ring of formula IIb include C, CH, or N at each ring position, where the single ring of formula IIa and the first ring and the terminal ring of formula IIb independently contain no more than two nitrogen atoms; Z in formulae IIa and IIb is CH2 or a direct bond, R1 is independently any one or two of H, F, C1, CF3, OCF3 or OCH2Ph, and R2 is H. The invention also relates to a pharmaceutical composition based on the compound of formula I, a method of preventing and treating a microbial infection based on use of the compound of formula , and specific nitroimidazooxazine derivatives.

EFFECT: obtaining novel compounds with useful biological activity.

7 cl, 21 dwg, 3 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to field of genetic engineering, molecular biology and vaccinology. Claimed is polyepitopic anti-tuberculosis vaccine construction for formation of immune response, which provides induction of immune response of CD8+ T-lymphocytes, consisting of universal polyepitopic immunogen, containing CTL-epitopes, selected from immunodominant antigens of M. tuberculosis, fused from N-end with ubiquitin, and having amino acid sequence SEQ ID NO: 1.

EFFECT: vaccine construction provides achievement of effective therapeutic T-cell immune response not only due to antigenspecific cytotoxic CD8+ T-lymphocytes but also intensive response of CD4+ T-lymphocytes.

1 tbl, 11 dwg

FIELD: medicine.

SUBSTANCE: invention concerns Mycobacterium tuberculosis growth inhibitors representing (+) and (-)-enantiomers of derivatives of usnic acid containing a furilidene furanone fragment, namely (10R,4Z)-8,13-dihydroxy-7,10-dimethyl-4-(2-furanylmethylidene)-5,16-dioxatetracyclo[7.7.0.02.6.010.15]hexadeca-1,6,8,12,14-pentaen-3,11-dione 4a and (10S,4Z)-8,13-dihydroxy-7,10-dimethyl-4-(2-furanylmethylidene)-5,16-dioxatetracyclo[7.7.0.02.6.010.15]hexadeca-1,6,8,12,14-pentaen-3,11-dione 4b

EFFECT: inhibitors possess the high antimicrobial activity.

2 tbl, 7 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel derivatives of 1-(2-chloroquinolin-3-yl)-4-dimethylamino-2-(naphthalen-1-yl)-1-phenylbutan-2-ol of general formula I or their pharmaceutically acceptable salts with acids, where R1 denotes H, R2+R3 denotes -O-(CH2)n-O-, where n=1-2, which forms additional dioxane and 1,3-dioxolane rings. The invention also relates to a method of producing a compound of formula I and to use of the compound of formula I in treating infectious mycobacterial diseases.

EFFECT: obtaining novel compounds with useful biological activity.

4 cl, 2 tbl, 3 ex

FIELD: medicine.

SUBSTANCE: for treatment of patients with pulmonary tuberculosis with accompanying non-specific bronchitis at the background of carrying out standard anti-tuberculosis therapy from the first day of treatment additionally daily for 3 months the preparation Wobenzym is introduced in a dose of 1 tablet 2 times per day, 30 minutes before meal, and inhalation with a solution of the preparation Hixozide in a dose of 350 mg in 10 ml of water for injections is performed 2 times per week, the course constitutes 24 procedures.

EFFECT: method makes it possible to increase treatment efficiency by indices of infiltration resorption, closing of the decay cavities and abacillation.

1 tbl, 2 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a cyclic compound containing the amino acid sequence GQRETPEGAEAKPWY in addition to one or two additive amino acids, and having no C-terminal carboxyl group and/or N-terminal amino group, where one of the amino acids is a synthetic amino acid, and wherein a ring is closed between a side chain of one amino acid and a C-terminal of the other amino acid, or the ring is closed by the synthetic amino acid; a method for preparing and using it to regulate vector ion channels for treating the diseases related to the pulmonary function, and for treating oedemas.

EFFECT: preparing the composition for treating the diseases related to the pulmonary function, and for treating oedemas.

16 cl, 16 dwg, 2 tbl, 9 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new bacitracin compounds with antibiotic activity

,

wherein at least one of R1, R2 and R3 represents -CH=CH2 and wherein R1, R2 and R3 independently represent -H, -CH3 or -CH=CH2.

EFFECT: preparing the new bacitracin compounds.

13 cl, 8 dwg, 7 tbl, 5 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new compounds of formula I and their pharmaceutically acceptable salts, method for preparing them by the fermentation of a microorganism of the species Streptomyces (PM0626271/MTCC 5447), and to their pharmaceutical compositions containing one or more compounds of formula I as an active ingredient.

EFFECT: compounds of formula I are used for treating and preventing the diseases caused by bacterial infections.

4 cl, 3 dwg, 6 tbl, 9 ex

FIELD: medicine.

SUBSTANCE: invention relates to biology and medicine and is aimed at the increase of efficiency of the tumour growth suppression with the application of recombinant human proteins, which bind with a receptor of cytokine TRAIL/Apo2L and trigger apoptotic death of tumour cells, without damaging normal cells. In particular the invention relates to a method of suppressing the tumour growth. The invention consists in the fact that the said recombinant proteins, binding with receptors of cytokine TRAIL/Apo2L, are applied in a combination with substances, which suppress resistance of the tumour cells to TRAIL proteins, and in addition to it cyclic peptide Cys-Arg-Gly-Asp-Lys-Gly-Pro-Asp-Cys is applied. It is supposed that the said peptide enhances the penetration of TRAIL from the vessels to the tumour cells.

EFFECT: application of a combination of recombinant TRAIL proteins and substances, which increase the sensitivity of the tumour cells to them, in a combination with the said peptide in accordance with the claimed invention, makes it possible to increase efficiency of the tumour growth suppression.

3 dwg, 3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to methods of preserving integrity of peptides in alimentary canal by application of chenodeoxycholic acid, ursodeoxycholic acid, glydeoxycholic acid, glycochenodeoxycholic acid or biguanide, which inhibit one or more serine proteases of intestine.

EFFECT: preservation of peptide integrity.

27 cl, 16 dwg, 13 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: group of inventions refers to medicine and concerns a method of treating meningioma in an individual in need thereof involving parenteral administration of a therapeutically effective amount of pasireotide or its pharmaceutically acceptable salt into the above individual; a compound for parenteral administration for treating meningioma containing pasireotide or its pharmaceutically acceptable salt together with one or more of their pharmaceutically acceptable solvents or carriers.

EFFECT: group of inventions provides better effectiveness and tolerance of pasireotide in patients with recurrent meningiomas than if applying the other treatment, eg with octreotide.

2 cl, 1 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to RGD-containing cyclic peptidomimetics, conjugates of the said peptidomimetics and a functional group, selected from fluorescent probes, photosensitisers, chelating agents or cytotoxic agents; and to pharmaceutical compositions, which contain the said conjugates.

EFFECT: conjugates by the invention are suitable both for diagnostic purposes and for treatment of different diseases, disorders and states.

26 cl, 9 dwg, 10 tbl, 13 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to pharmaceutical industry and represents medication, which has a nootropic action on an organism based on cyclic dipeptides, which contains a propyl-alanine sequence.

EFFECT: invention ensures extension of arsenal of medication with nootropic activity.

2 cl, 2 ex, 2 tbl

FIELD: medicine.

SUBSTANCE: invention refers to medicine. Treating nosocomial sinusitis in resuscitation and intensive care units is ensured by nasal cavity clearance and sinus irrigation according to the common technique using a Kulikovsky's needle. The solution of polymyxin E in the concentration of 133 mcg/ml is introduced for 10 minutes before sinus administration of a photosensitiser that is methylene blue 20 ml in the concentration of 15 mcg/ml. The contents are aspirated with a syringe. The sinus mucosa is exposed to laser light through a dissipative light guide introduced through the Kulikovsky's needle at wave legnth 660 nm, power 500 mWt, emission length 23.5 minutes.

EFFECT: method enables enhancing the photodynamic effect on the gram-negative microorganisms ensured by including polymyxin E relieving the photosensitiser adhesion on the surface of a gram-negative bacterial cell into the method of the photodynamic therapy.

2 tbl, 2 ex

Peptides // 2496789

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a conformationally restricted cyclic oligopeptide producing two stable and specific epitopes each of which is able to react with a target ligand, to a pharmaceutical composition comprising the above oligopeptide, and to a method for producing the oligopeptide.

EFFECT: producing the conformationally restricted cyclic oligopeptide.

19 cl, 8 tbl, 8 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to clinical microbiology and antimicrobial chemotherapy, and concerns developing and creating new combinations providing potentiating bactericidal action and effectively inhibiting the purulent infection caused by methicillin-resistant S. aureus by using two classes of compounds possessing the essentially different mechanism of antimicrobial action.

EFFECT: developing and creating the new combinations providing potentiating bactericidal action and effectively inhibiting the purulent infection.

2 dwg, 6 tbl

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