Method of preventing cerebral form of radiation sickness

FIELD: medicine.

SUBSTANCE: invention relates to medical radiology and can be used for prevention of cerebral form of acute radiation sickness. Claimed is application of officinal drug pyrazinamide as medication for prevention of cerebral form of acute radiation sickness. Pyrazinamide has been used for treating tuberculosis.

EFFECT: preventing in 100% of cases development of early temporary incapacity in case of irradiation in dose 200 Gy, improvement of indices of behavioral and research activities in irradiated animals, in reduction of frequency of motor disorders, reduction of frequency and expression of convulsive-hyperkinetic syndrome and 9,5 fold increase of average life expectancy of irradiated animals Pyrazinamide is not inferior to drug - nicotinamide prototype in efficiency of radioprotective action.

4 tbl, 4 ex

 

The invention relates to the field of medicine and veterinary medicine, namely, medical radiology, and can be used for the prevention of cerebral form of acute radiation sickness (ARS).

The widespread introduction of nuclear technologies in all spheres of human activity (industrial production, energy, science, medicine and others) leads to an increase in the total number of radiation-hazardous facilities and the steady improvement of the probability of occurrence of radiation accidents. In this regard, a reliable radiation protection, including pharmacological, is a necessary condition to ensure the work of many professionals, especially those in risk groups (cosmonauts, plant personnel, polygons, institutes of nuclear physics, nuclear power and research facilities, personnel, emergency services, military, etc), emergency and other extreme situations. In addition, there are good reasons to believe that one of the real threats in the modern world is the ability to use weapons, the main damaging factor which are ionizing radiation (AI) at high energies.

Given the variety of possible options for the effects of radiation on humans, it should be noted that the number of persons professionally exposed to the risk of exposure to AI in excess of the high doses (of the order of tens and hundreds of gray), will continue to grow, and the problem of protecting them from radiation injuries for many decades will remain relevant.

The risk of human exposure to radiation at high doses is associated with the fact that during or immediately after exposure, development is observed distinct disorders of the Central nervous system (CNS), leading to a rapid loss of capacity. Such violations are associated with the development of complex characteristic syndromes, such as convulsive agents, neurological, cardiovascular, behavioral disorders and other, United in the so-called cerebral radiation syndrome (SSC) [1, 2]. For SSC phase is characterized by a period when, following a period of excitation should deep weakness, against which possible spells hyperkinesia and convulsions lasting for several hours before the onset of terminal (comatose) status.

In this regard, the finding of drugs for the prevention of disorders of the Central nervous system in terms of impact on human AI in excessive doses, is one of the topical problems of modern medical radiology. Pharmacological correction of abnormalities in SSC is a necessary condition for the normal functioning of persons professionally associated with the risk of exposure of organisms is in emergency and other extreme situations [3].

For the prevention of disorders of the Central nervous system, resulting from the impact of AI in excessive doses, use of pharmacological means - "cerebral" radioprotectors, which provide temporary preservation of the health of the organism in such situations. From a number of known means, manifesting in experiments on animals properties "cerebral" radioprotectors, some interest: pentobarbital [4], benzamide [5] and some of its derivatives, for example 3, N, butylimidazole [6, 7] and nicotinamide [8-10].

However, these drugs cannot be considered fully meet the basic requirements of the "cerebral" radioprotectors. So, pentobarbital refers to the soporific means that preclude their use as a means of preserving the health of a person in extreme situations, associated with its exposure. From the available information benzamide and its derivatives is known that they exhibit properties "cerebral" radioprotectors. But these tools are at the stage of laboratory tests and still are not officinal drugs. Thus, at present, they cannot be considered available as a "cerebral" radioprotectors.

Nicotinamide is among officinal the different drugs from the group of vitamins. However, it comes in dosage forms in which the active ingredient contained in doses of not more than 50 mg It is not enough to ensure prevention of SSC [8] because it is known that the estimated one-time radioprotective dose of nicotinamide for a man is not less than 1.0 g, which is achieved in the case of taking 20 tablets of 0.05 g [10]. This fact severely limits the possibilities of practical use of nicotinamide as a "cerebral" radioprotector. Belonging to the number of pharmaceutical drugs and the achieved effect of nicotinamide closest to the proposed facility and adopted as a tool prototype.

Thus, considered the drugs currently one reason or another are unable to find application as a widely available means of preventing cerebral form ARS.

The aim of the invention was expanding Arsenal of pharmacological prophylaxis SSC, resulting in exposure of ionizing radiation in high doses, due to the use of drugs having similar compared to vehicle-prototype, efficiency, also which is the officinal drug, but it is much more affordable for mass application

This goal is achieved by CA is in the drug pyrazinamide, who is a domestic officinal drug intended for the treatment of tuberculosis. Single dose of pyrazinamide for adults is 1.0-2.0 g that corresponds to an estimated radioprotective dose of "cerebral" radioprotectors. In the pharmacy network comes in the form of tablets weighing 0.25 g 0.50 g [11]. In the case of pyrazinamide for a new purpose radioprotective dose of the drug can be achieved by the intake of 2 tablets of 0.5 g Information about the use of pyrazinamide as "cerebral" radioprotector in the available literature is not found.

The possibility of achieving the goal of the invention the following examples.

Example 1. Determination of the optimal dose of the inventive means to influence the severity of disorders of the Central nervous system in irradiated rats.

The experiments were carried out on outbred rats-males weighing 180-200 g Of the experimental animals were formed 3 groups: a control and two experimental. In the experiment, the animals were subjected to General relatively uniform gamma irradiation at a dose of 200 Gy.

Animals of the control group for 15-30 min before irradiation were injected intraperitoneally with 0.9% sodium chloride solution in a volume of 0.5 ml per rat. Tool-prototype (nicotinamide) was administered to the animals of the first experimental group that did in the optimal time, i.e. for 15-30 minutes before the Lucania, intraperitoneally in an optimal dose, 100 mg/kg Animal the second experimental group for 15-30 min before irradiation was administered the inventive tool (pyrazinamide) intraperitoneally at various doses (50, 100 and 150 mg/kg).

During the observation of irradiated animals for 6 h were recorded in each experimental group the number of animals with signs of early transient incapacitation (RPN), as well as its duration and severity. Statistical processing of monitored parameters was carried out using the U-test, Mann-Whitney. The differences were considered significant at p≤0,05.

The experimental results showed that the impact of AI in a dose of 200 Gy leads to the development of RPN in 100% of animals in the control group. The duration of disability was 64±28 min (table 1).

Prophylactic administration tools the prototype at the optimal time and the optimal dose in 100% of cases completely prevented the development of disorders of the Central nervous system in experimental irradiated animals.

In the case of using the proposed tools are installed, that preventive his introduction in a dose of 50 mg/kg, prevented the development of RPN in 42% of the test animals. However, the duration of the incapacity of the remaining 58% of the rats was 33±13 minutes but the Introduction of the proposed drug in doses of 100 mg/kg and 150 mg/kg completely before is rotated development of RPN in irradiated animals.

Experimentally it was found that the lowest dose of the claimed means of preventing the development of disorders of the Central nervous system, is 100 mg/kg, this dose of the inventive tool was used in further studies.

Thus, the prophylactic use of the proposed drug in a dose of 100 mg/kg prevents the development of RPN in 100% of animals irradiated at a dose of 200 Gy.

Example 2. The study of the influence of the means of the prototype and the proposed drug on the level of orienting-exploratory activity of irradiated rats in the open-field test.

The experiments were carried out on outbred rats-males weighing 180-200 g Of the experimental animals were formed 4 groups: intact control and two experimental. In the experiment, the animals of the control and experimental groups were introduced by various means, as described in example 1 and then exposed them to a common relatively uniform gamma irradiation at a dose of 200 Gy.

Intact and irradiated rats (immediately after exposure) was tested for 3 min using the method of "open field". Assessed locomotor activity in experimental animals (number of crossed squares and the time of immobility), and research activity (the number of vertical columns and mink reactions) [12]. Statistical processing of experimental data wire, and using U-test, Mann-Whitney. The differences were considered significant at p≤0,05.

The experimental results showed that irradiation leads to a pronounced inhibition of behavioral activity in experimental animals. General locomotor activity of irradiated rats of the control group, measured in the open-field test, decreased by 3.6 times, and research - 4.5 times compared to the level of this indicator in the intact group. The data in table 2 show that irradiated at a dose of 200 G. the animals were crossed 20±6 squares, and they fixed the seat was 150±18 C. indicators of research activity, namely the number of vertical columns and mink reactions was 5±3 and 3±2, respectively.

Prophylactic administration tools the prototype contributed to the fact that after exposure to AI at a dose of 200 Gy behavioral activity in experimental animals compared with the control group is significantly higher, as evidenced by the increase in the number of crossed squares in 2.4 times and decrease during the stationary seat rats 5.6 times. This research activity in experimental animals is also higher than in the control group. The number of vertical columns and mink reactions have increased 2.6 times and 2.7 times.

In the case of prevention of the introduction of the proposed drug also observed and improvement in behavioral and research activities in irradiated animals compared with the control group. This is evidenced by the increase in the number of crossed squares in 2,3 times and decrease during the stationary seat rats 6.0 times. The number of vertical columns and mink reactions have increased 2.2 times and 2.3 times.

Thus, it is found experimentally that the proposed remedy for the efficacy of preventive effects on locomotor and exploratory activity in experimental irradiated animals is not inferior to the tool prototype.

Example 3. The study of the influence of the means of the prototype and the proposed drug on the ability of irradiated rats to perform memorized the tests in the test Beam-walking.

The experiments were carried out on outbred rats-males weighing 180-200 g Of the experimental animals were formed 4 groups: intact control and two experimental.

To test the "Beam-walking rats of all experimental groups pre-trained for 3 days to cross the beam width of 2.5 cm and a length of 122 cm, located at a height of 100 cm from the floor [13]. Upon completion of training in experimental animals of the control and experimental groups were introduced by various means, as described in example 1 and then exposed them to a common relatively uniform gamma irradiation at a dose of 200 Gy.

Experimental intact and irradiated animals (immediately after exposure) were tested on the bar. The assessment is rabotosposobnosti was performed according to the total time spent by the rat in the intersection of the crossbar and severity of musculoskeletal disorders. Statistical processing of results of research conducted by U-test, Mann-Whitney. The differences were considered significant at p≤0,05.

Testing of rats on the crossbar has allowed to establish that the irradiation leads to a significant increase in the time of intersection of the crossbar of animals in the control group. As can be seen from the data presented in table 3, rats irradiated at a dose of 200 Gy, crossed the crossbar for the 104.3±27,2 C. With 75% of the animals observed significant violations in the nature of physical activity. Some of them was not even able to stay on the crossbar (2 of 12 rats).

A different picture was observed in the case of prophylactic insertion of the prototype. Average time crossing beams irradiated rats 1 experimental group was 22.6±4,8, and the frequency of musculoskeletal disorders is 25%. In comparison with the indices of the control group the average time of intersection of the crossbar decreased 4.6 times, and the frequency of musculoskeletal disorders - 3.0 times.

A similar pattern was observed in the case of prophylactic use of the proposed drug. The introduction of the proposed drug has reduced the crossing time of the crossbar to 17.3±3,3 with motor impairment was observed in 3% of the test animals. In comparison with the indices of the control group the average time of intersection of the crossbar and the frequency of musculoskeletal disorders decreased, respectively, 6.0 times and 2.3 times.

Thus, the experimentally using test Beam-walking" established that the claimed means of influence on the indicators of behavioral activity of rats irradiated at a dose of 200 Gy, is not inferior to the tool prototype.

Example 4. The study of the influence of the means of the prototype and the proposed drug development frantically-hyperkinetic syndrome.

The experiments were performed on Guinea pigs weighing 300-350 g Of the experimental animals was formed 3 groups: a control and two experimental. In the experiment, animals were injected with various means, as described in example 1 and then exposed them to a common relatively uniform gamma irradiation at a dose of 200 Gy.

The criteria for the effectiveness of preventive action for the tested tools were the incidence and intensity of shivering-hyperkinetic syndrome, occurred in experimental animals as a result of their exposure. Aggregation of controllable parameters in the experimental groups was performed using U-test, Mann-Whitney. The differences were considered significant at p≤0,05.

The results of these studies are presented in table 4, indicate that irradiation alive who were in the control group led to the development of seizures in 100% of cases. When seizures occurred spontaneously or was provoked through 20-40 min after irradiation and gradually became more frequent. After 2-5 h on the background of epileptic status developed decerebration realnosti. The life span of irradiated animals did not exceed 24 hours

The use of the prototype was characterized by the absence of generalized seizures in irradiated animals throughout the observation time (36 h after irradiation). It should be noted that in 30% of cases there was a tremor the muzzle and front legs. The life span of irradiated animals was 6.2±1,3 d, that is, in comparison with the specified index of the control group increased in 10 times.

Prophylactic injection in the same conditions of the proposed drug generalized seizures were not observed, the tremor was found in 25% of cases. The average life expectancy of irradiated Guinea pigs was 5.7±2,2 day, that is compared with the specified index of the control group increased by 9.5 times.

Thus, it is found experimentally that the proposed remedy for the impact on the frequency and severity of frantically-hyperkinetic syndrome in Guinea pigs is not inferior to the tool prototype.

The obtained experimental data indicate the goal of the invention is the expansion of the Arsenal FA is metologicheskikh prophylaxis of cerebral radiation syndrome due to use as a "cerebral" radioprotector registered officinal drugs pyrazinamide, not inferior in efficacy officinal drug nicotinamide (tool prototype).

The proposed remedy meets the criterion of "novelty", as for the first time to prevent the development of cerebral radiation syndrome in terms of the effects of ionizing radiation in high doses it is proposed to use officinal drug pyrazinamide, which helps prevent the development of disorders of the Central nervous system.

The proposed remedy meets the criterion of "inventive step", since on the basis of available information, the feasibility of using pyrazinamide as "cerebral" radioprotector and the possibility of effective prevention of the manifestations of cerebral form of acute radiation sickness does not seem obvious.

The compliance of the claimed invention, the criterion of "fitness for use" is confirmed by the results of this study showed high efficacy of the drug pyrazinamide for prevention of development of cerebral radiation syndrome in terms of the effects of ionizing radiation in high doses. The drug is an officinal drug and is available for practical use for a new purpose in the dosage form in which it arrives in the pharmacy network.

Sources of information

p> 1. Legeza Century. And. To the question of patanasepatanase mechanisms early reaction to radiation at high doses / Century And. Legeza, Y. S. Turlakov // Radiobiological Congress. Pushchino. 1983. Kiev 20-25.09.1993. - S. 584-585.

2. Malakhovsky Century. N. Acute radiation cerebral disorders as the effect of DNA damage neurons / C. N. Malakhovsky // Radiobiology. - 1993. - T. 33, vol.3. - S. 392-397.

3. Maalouf M. Biological Effects of Space Radiation on Human Cells: History, Advances and Outcomes / M. Maalouf, M. Durante, N. Foray // J. Radiat. Res. - 2011. - Vol.52. - P. 126-146.

4. Andrews, H. L. Medication of early radiation death in guinea pigs / H. L. Andrews, K. C. Brace // Am. J. Physiol. - 1956. - Vol. 187, No. 2. - P. 378-380.

5. Ilyin, L. A. Pharmacological prophylaxis of cerebral form of acute radiation sickness / L. A. Ilyin, K. S. Martirosov, centuries Zorin // VI Congress on radiation research (radiobiology, radioecology, radiation safety). The abstracts. So 1. Moscow, 25-28 October 2010 - M.: PFUR, 2010. - S. 193.

6. EN 2229882 C2, 10.06.2004.

7. Krasil'nikov, I. I. Benzamide as the structural basis of new drugs with a broad spectrum of biological activity / I. I. Krasilnikov, O. F. Alferov, A. C. Stepanov, G. C., Tsikarishvili // Chem. Pharm. Journe. - 1995. No. 8. - S. 19-22.

8. Mashkovsky M. D. Drug / M. D. Mashkovsky. - Ed. 13-E. - Kharkov: Torsing, 1997. - T. 2. - S. 93.

9. Tikhomirov P. C. the Effect of inhibitors of poly-ADP-ribosylate on the state of GABAergic receptors in irradiated and in high doses / P. C. Tikhomirov, A. Y. Kondakov // Russian conference "urgent problems of development of radioprotective funds: conservatism or modernization." The abstracts. Moscow, 13-14 November 2012 - M.: PFUR, 2012. - S. 60.

10. Legeza Century. And. Medical devices radiation protection: a Handbook for clinicians / edited by C. I. of Legaz and A. N. Grebenyuk. - SPb.: Publishing house "LAN", 2001. - 95 S.

11. Mashkovsky M. D. Drug / M. D. Mashkovsky. - Ed. 14-E. - M.: New wave, 2002. - T. 2. - S. 310-311.

12. Bureš J. Techniques and basic experiments for the study of brain and behavior / J. bureš, O., Buresova, J. Houston. M. - 1991. - 399 S.

13. Goldstein L. B. Beam-walking in rats: studies towards developing an animal model of functional recovery after brain injury / L. B. Goldstein, J. N. Davis // J Neurosci Methods. - 1990. - Vol.31, No. 2. - P. 101-107.

Prophylaxis of cerebral form of acute radiation sickness

Table 1
The impact of the funds of the prototype and the proposed drug on the severity of an early transient incapacitation (RPN) rats irradiated at a dose of 200 Gy
The group of animalsThe number of irradiated animalsDose, mg/kgThe number of animals with impaired spontaneous motor activity The average duration of RPN, min
The control (treated with 0.9% sodium chloride solution)12-2464±28
1 experimental (treated with the vehicle-prototype)121000*0*
2 experimental (treated with the inventive tool)12505*33±13
121000*0*
121500*0*
Note. * - differences significant (p≤0.05) as compared with the control group

Table 2
The impact of the funds of the prototype and the proposed drug on indicators of behavioral activity of rats irradiated at a dose of 200 Gy, estimated using the method of "open field" (M is m, n=12 in each group)
The group of animalsIndices of locomotor activityIndicators of research activity
The number of crossed squaresThe time fixed seat,The number of vertical racksThe number of mink reactions
The intact44±526±510±29±3
The control (treated with 0.9 % sodium chloride solution)20±6150±185±33±2
1 experimental (treated with the vehicle-prototype)48±15*27±13*13±5*8±2*
2 experimental (treated with the inventive tool)45±13*25±8*11±4*7±4*
Note. * - the differences among Erny (p≤0.05) as compared with the control group

Table 3
The impact of the funds of the prototype and the proposed drug on indicators of behavioral activity of rats irradiated at a dose of 200 Gy, measured using test Beam-walking" (M±M, n=12 in each group)
The group of animalsIndicators of behavioral activity
The crossing of the beams, withThe number of animals with movement disorders, %
The intact5,2±2,90+8
The control (treated with 0.9% sodium chloride solution)the 104.3±27,275±13
1 experimental (treated with the vehicle-prototype)22,6±4,8*25±13*
2 experimental (treated with the inventive tool)17,3±3,3*33±14*
Note. * - differences significant (p≤0.05) as compared with the control group

Prophylaxis of the Church is Braley form of acute radiation sickness

Table 4
The impact of the funds of the prototype and the proposed drug on the incidence frantically-hyperkinetic syndrome in Guinea pigs irradiated at a dose of 100 Gy (n=12 in each group)
The group of animalsDevelopment indicators frantically-hyperkinetic syndrome
The number of animals with convulsive syndromeLife expectancy M±M, d
The control (treated with 0.9% sodium chloride solution)120,6±0,4
1 experimental (treated with the vehicle-prototype)0*6,2±1,3*
2 experimental (treated with the inventive tool)0*5,7±2,2*
Note. * - differences significant (p≤0.05) as compared with the control group

The use of pyrazinamide as a means of preventing cerebral form of acute radiation sickness.



 

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FIELD: medicine, pharmaceutics.

SUBSTANCE: compounds can find application for preventing or treating cancer, lung cancer, non-small cells lung cancer, small-cell lung cancer, EML4-ALK hybrid polynucleotide-positive cancer, EML4-ALK hybrid polynucleotide-positive lung cancer or EML4-ALK hybrid polynucleotide-positive non-small cells lung cancer. In formula (I) -X-: group of formula , A represents chlorine, ethyl or isopropyl; R1 represents phenyl wherein carbon in the 4th position is substituted by the group -W-Y-Z, and carbon in the 3rd position can be substituted by a group specified in a group consisting of halogen, R00 and -O-R00; R00: lower alkyl which can be substituted by one or more halogen atoms; -W-: a bond, piperidine-1,4-diyl or piperazine-1,4-diyl; -Y- represents a bond; Z represents a monovalent 3-10-membered monocyclic non-aromatic heterocyclic ring which contains 1 to 4 heteroatoms specified in a group consisting of nitrogen, oxygen and sulphur, which can be substituted by one or more substitutes R00; R2 represents (i) an optionally bridged saturated C3-10cycloalkyl which can be substituted by one or more groups specified in -N(lower alkyl)2, lower alkyl, -COO-lower alkyl, -OH, -COOH, -CONH-RZB and morpholinyl, or (ii) a monovalent 3-10-membered monocyclic non-aromatic heterocyclic ring which contains 1 to 4 heteroatoms specified in a group consisting of nitrogen, oxygen and sulphur, which can be substituted by one or more groups specified in a group consisting of lower alkyl, -CO-lower alkyl, oxo, -CO-RZB and benzene; and RZB: phenyl which can be substituted by a group consisting of halogen and -O-lower alkyl; R3 represents -H.

EFFECT: invention refers to new compounds of formula or their pharmaceutically acceptable salts possessing the properties of a selective inhibitor of EML4-ALK hybrid protein kinase activity.

16 cl, 201 tbl, 582 ex

FIELD: chemistry.

SUBSTANCE: claimed is a cocrystalline form of fenbufen with pyrazinamide, where molar ratio of fenbufen with pyrazinamide constitutes 1:1, which has an endothermal peak from 148 to 152°C by the data of measurements by means of differential scanning calorimetry and peaks at 2θ(°) 7.38, 10.43, 11.04, 21.67 by the data of measurement of polycrystal X-ray radiation diffraction.

EFFECT: increased rate and level of solubility of the crystalline form of fenbufen and its suitability for application in the pharmaceutical industry.

2 ex, 7 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: there are presented: a product for treating pulmonary arterial hypertension containing macitentan or its pharmaceutically acceptable salt in a combination with a prostacyclin receptor (IP) agonist specified in iloprost, beraprost, 2-{4-[(5,6-diphenylpyrazin-2-yl)(isopropyl)amino]butoxy}-N-(methylsulphonyl)acetamide, {4-[(5,6-diphenylpyrazin-2-yl)(isopropyl)amino]butoxy}acetic acid or their pharmaceutically acceptable salt (versions), a pharmaceutical composition for the same application and formulation of the active agents. What is also presented is using macitentan or its salt in a combination with the above agonist for preparing the therapeutic agent for treating pulmonary arterial hypertension.

EFFECT: what is shown is synergic action (double effect) of the declared combinations

10 cl, 1 tbl, 1 ex

FIELD: chemistry.

SUBSTANCE: in formula 1 , X denotes a negative charge which is localised on a fullerene skeleton, a chlorine atom bonded to a carbon skeleton or a hydrogen atom; the NR1R2 moiety denotes an amine residue, where R1 and R2 are hydrogen atoms or linear or branched alkyl radicals (CmH2m+1; n=1-20) that are substituted with protonated (NH3+) or unprotonated (NH2) amine groups, or a piperazine residue of general formula 1c-1 , where R, R'1, R'2, R'3 and R'4 are hydrogen atoms or linear or branched alkyl (CmH2m+1; n=1-20) radicals, as well as residues of aliphatic alcohols -(CH2)nOH, ethers -(CH2)nOR'5, thiols -(CH2)nSH, acids -(CH2)nCOOH, esters thereof -(CH2)nCOOR'5 or amides -(CH2)nCONR'5R'6, for which n=0-20, R'5 and R'6 are hydrogen atoms or linear alkyl (CmH2m+1; n=1-20) radicals.

EFFECT: stronger or prolonged antibacterial action.

2 cl, 2 dwg, 2 tbl, 3 ex

Fibrosis inhibitor // 2497525

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutics and medicine and concerns a fibrosis inhibitor containing 2-{4-N-(5,6-diphenyl-pyrazin-2-yl)-N-isopropylamino]butyloxy}acetic aci or a pharmaceutically acceptable salt thereof or 2-{4-[N-(5,6-diphenyl-pyrazin-2-yl)-N-isopropylamino]butyloxy}-N-(methylsulphonyl)acetamide or a pharmaceutically acceptable salt thereof as an active ingredient for treating interstitial pneumonia, pulmonary fibrosis, scleroderma or hepatic cirrhosis.

EFFECT: inhibitor provides high efficacy.

6 cl, 0 dwg, 6 ex

FIELD: pharmaceutical industry.

SUBSTANCE: invention provides composite therapeutical agent exhibiting antituberculous effect and made in the form of solid dosage form containing as active principle combination of lomefloxacin, isoniazid, pyrazinamide, ethambutol hydrochloride, and pyridoxine hydrochloride plus auxiliaries.

EFFECT: increased assortment of antituberculous drugs.

4 cl, 1 tbl, 4 ex

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