Rifampicin-based medication with prolonged action for treatment of resistent forms of tuberculosis
SUBSTANCE: invention relates to field of pharmacology and medicine and represents rifampicin-based medication of prolonged action for treatment of resistant tuberculosis forms, which is different because it represents stable nanoparticles and contains rifampicic, biodegradable polymer of lactic acid or copolymer of lactic and glycolic acid, as well as surface active substance, cryoprotector, components in medication being in specified ratio in wt %.
EFFECT: invention ensures reduction of risk of toxic effects, prolonged action and reduction of intake factor in treatment.
6 cl, 3 ex, 1 tbl, 1 dwg
The invention relates to the field of pharmacology and medicine, specifically to a new generation of antimicrobial and anti-TB drugs are regulated actions on the basis of 3-[[(4-methyl-1-piperazinil)imino]-methyl]rifamycin or 5,6,9,17,19,21-hexahydroxy-23-methoxy-2,4,12,16,18,20,22-heptamethyl-8-[N-(4-methyl-1-piperazinil)-formimidoyl]-2,7-epoxyphenolic[1,11,13]trientine)oil-[2,1-b]furan-1,11(2H)-dione-21-acetate (rifampicin).
According to the who in 2006 was 9.2 million new cases of tuberculosis (139 per 100,000). It is 100 thousand more than in 2005, In 2006, died of tuberculosis 1.7 million people. In Russia in 2007, the number of patients with multidrug resistance among new cases was 4149 people (9.8% of the total number of newly diagnosed). Just consists on the account at the end of 2007 - 24445 people per 100 thousand population.
A similar pattern is observed with the incidence of gastrointestinal tract, upper and lower respiratory tract, etc. caused by various microorganisms, resistant to most contemporary antibiotics.
One of the modern antibiotic with a broad antibacterial and germicidal action spectrum is a semisynthetic drug rifampicin. Rifampicin is active against M. tuberculosis and therefore widely uses the I for the treatment of tuberculosis in combination with other drugs. The antibiotic is also used for infections of skin, soft tissue, the treatment of pneumonia, lung abscesses, cholecystitis, etc.
The resistance of mycobacteria to rifampicin is developing rapidly, which is a big drawback of antibiotics in this series.
Another negative property of rifampicin is its poor absorption when administered, consequently, it is necessary to apply parenteral.
Rifampin and other antibacterial and bactericidal drugs, has low selectivity of action and with the introduction of the antibiotic patients only a small dose gets into the target cell. A large part of biotransformation and excreted from the body, not having therapeutic effect. In this regard, during treatment with rifampicin, especially its long-term use, recorded numerous adverse effects: allergic reactions (skin rash, eosinophilia), nausea, vomiting, increased liver transaminases in the blood, headache, arthralgia, tubular necrosis, impaired vision, the development of thrombophlebitis and other Rifampin is contraindicated in patients with impaired liver and kidney, pregnant women and during lactation .
To solve the problems associated with the toxicity of drugs, contraindications, resistance and so on, it is necessary to solve for the ACI to improve the effectiveness of drugs and therefore, reducing therapeutic dose and toxic effects. The most significant of the possible ways of achieving this goal is the development of drugs or dosage forms which are focused on delivering and localization of drugs in target cells in effective therapy doses. While it is desirable that this property combined with a long gradual release of substances (prolongation of action)that allows you to create a more comfortable environment for patients, displaced regularly and long-term use of drugs.
A new technical result is achieved by the totality of all existing signs created medicines on the basis of rifampicin to achieve positive pharmacodynamic activity of the drug at lower doses and thereby reduce the risk and the degree of occurrence of toxic effects, while achieving the effect of prolongation of the action, reducing the multiplicity of admission for treatment.
The technical result of the invention is achieved through the inclusion of a new drug on the basis of rifampicin, commercially available biodegradable polymers approved for medical use, for nanoparticles. As such used: polylactic acid (PLA), copolymers of glycol is eve and lactic acid (PLGA) and a copolymer of glycolic and lactic acid with a free carboxyl end group (PLGA-COOH).
For nanoparticles used polymers with a molecular mass of from 10 to 300 kDa and a molar ratio of the residues of lactic and glycolic acids from 25:75% to 50:50%. To obtain a stable dosage forms, representing the nanoparticles size of 200-500 nm and having a slow release of antibiotic, are also used surfactants include Polysorbate 80, polyvinyl alcohol (PVA), poloxamer 188, serum albumin and cryoprotectants: mannitol, lactose, glucose and other sugars. The proposed tool get known method simple (single) emulsification (water/oil) . Sorption of rifampicin nanoparticles inside the polymer occurs when the removal of organic solvent from the resulting emulsion, and in the process of formation of the suspension.
It should be noted that earlier similar studies were conducted with Indian, Japanese and Iranian researchers [3-7]. In the works of Indian scientists [3, 4] described getting nanopreparations on the basis of PLGA enabled in the polymer matrix rifampicin, isoniazid, protionamide and ethambutol by ultrasonic emulsification. Preparations showed in vivo high antituberculosis activity within 10 days, while in our case the high activity was maintained and 21 days after the beginning of the experiment. In [3, 4] the absence of Tvout data on the toxic properties of drugs and therefore it is difficult to judge the prospects of their further use.
In the article the Iranian authors  provides data to obtain nanoparticle preparations (209÷260 nm) on the basis of PLGA with rifampicin and the study of their physico-chemical properties. Brief description of the data for the study of in vitro antibacterial activity in cell cultures. The in vivo experiments, not shown.
In  described experiments for obtaining particulate matter (less than 3 µm) on the basis of PLGA and antituberculosis drugs (isoniazid, rifampicin and pyrazinamide) by the method of double emulsification. The studied LV distribution in various organs of experimental animals after administration of these drugs over time. It is shown that the concentration of rifampicin and its activity was decreased after 9 days after injection. Information about the long-term effects of the drugs is not given. Similar information is presented in the work of Barrow E.L.W. and others , which describes a method of obtaining microspheres (7,5÷15 μm) of polymers of PLGA different composition adsorbed rifampicin. Data on the presence of activity on Mycobacterium tuberculosis for 6 days .
Thus, the aggregate of all existing signs created medicines: the presence of prolonging effect, the presence of high specific activity in vivo in animal experiments, infected with drug-resistant forms of TB, even after 3 weeks, yienna toxicity, achieved a new technical result.
The invention is illustrated by the following examples.
Example 1. Obtaining polymeric nanoparticles incorporating rifampicin method simple emulsions
A mixture consisting of a solution of 5÷60% polymer (PLA, PLGA or PLGA-COOH) and 1÷10% of rifampicin in an organic solvent (chloroform, methylene chloride), and 0.5÷2% aqueous solution of polymeric stabilizer emulsion in a volume ratio to the organic solvent of 5:1 homogenized at about 24 thousand./min on the homogenizer Ultra-Turrax T-25 (IKA®(Germany) 3 times for 1 min with intervals for 1 min Emulsion is stirred for 1 h at 40°C (if used chloroform) or 1.5 h at room temperature (if using methylene chloride) to complete removal of the organic solvent. This operation should be done when working exhaust ventilation. The resulting suspension is filtered through a coarse glass filter (pore. 40÷110 μm), added to the filtrate 1÷3% (vol.) cryoprotectant (D-mannitol), frozen and lyophilizers. The average particle size, determined by the method of autocorrelation spectroscopy on submicron laser spectrometer Coulter N4MD (USA), ranges from 250 to 500 nm, which facilitates the efficient absorption in the gastrointestinal tract . The size of the particles depends on the type of polymer is, stabilizer emulsion, their concentration, and homogenization. The degree of inclusion of rifampicin in the polymer particles is from 15 to 75%.
|Composition 1 (example 1)||wt.%|
|Polyvinyl alcohol :||15,2|
|Particle size||378±84 nm|
|Part 2 (of example 1)||wt.%|
|PLGA 50: 50||58,3|
|Polyvinyl alcohol :||16,6|
|Particle size||281±73 nm|
|Part 3 (example 1)||wt.%|
|Particle size||324±57 nm|
The optimal dilution means in the water corresponds to the ratio of from 1:20 to 1:10 that may be used to adjust the dosing of the drug depending on the individual patient.
The medicinal product is obtained according to claim 1, may be made in the form of tablets, capsules, granules, powder or other oral forms on the basis of known technologies [9, 10].
Example 2. Comparative pharmacological efficacy of the original drug prolonged action on the basis of rifampicin
Impact studies developed medicines on the basis of rifampicin on the survival and inoculation .tuberculosis in the lungs was conducted on a model of acute tuberculosis by injecting a lethal dose (.tuberculosis strain H37Rv at a dose of 5·106/mouse). Introduction drug prolonged action on the basis of rifampicin (PH), obtained in example 1, was started one day after playing TB. The drug was administered for 3 days. As a comparison, the por is performed experiments under similar conditions, where instead of a new drug rifampicin used or saline () or substance rifampicin (R). After completion of the experiment, animals were subjected to euthanasia by action geksenala, were removed and homogenized lungs were sowing to determine the number of viable .Tuberculosis. The data obtained are presented in table 1 and in the drawing.
|Comparative pharmacological efficacy of a drug action prolonged action on the basis of rifampicin|
|Medication||Stated value||Dose||Inoculation .tuberculosis in the lungs, the number of bacilli, CFU*/mouse|
|7 days||14 days||21 days|
|Control (physiologic solution)||To||1.0 ml||(3,7±1,22)×105||(1,6±0,06)×107||(2,6±0,68)×109|
|Rifampicin substance||P||20 mg/mouse||(7,3±0,06)×103||(1,7±0,17)×105||(4,6±0,56)×107|
|Medicinal product on the basis of rifampicin||PH||20 mg/mouse||(1,2±0,2)×103||(7,9±0,9)×103||(2,03±0,08)×105|
|Rifampicin substance||P||10 mg/mouse||(2,3±0,08)×104||(1,3±0,16)×106||(1,8±0,65)×109|
|Medicinal product on the basis of rifampicin||PH||10 mg/mouse||(6,3±0,07)×103||(5,3±0,16)×104||(1,06±0,06)×106|
|Note. the controls were injected with saline in a volume, equal to the volume of the injected drug; *CFU - colony forming unit.|
From table 1 and the drawing data shows that obtained in example 1 preparation on the basis of rifampicin with prolonging effect, also has superior activity of the parent substance - rifampicin. This is particularly evident through the 14th and 21st day after the start of the experiment, and when the drug concentration of 10 mg/mouse, when rifampicin (substance) almost ceases to act on the 21st day. This may allow to reduce therapeutic dose of rifampicin and thereby reduce the level of toxic side effects. Treatment of acute experimental tuberculosis in mice given the drug by the developed scheme allows to reduce the content of mycobacteria in the lung tissue is more than 100 times in comparison with the free rifampicin, reduce dosing frequency to 3 introductions by prolongirovannomu actions developed drug.
Example 3. Toxicological characteristics of the original drug prolonged action on the basis of rifampicin
A comparative study of the acute toxicity of the substance of rifampicin and developed polymeric drug based on it (the composition of example 1) were performed on mice male Balb weight 19÷21 GK the moment of testing. Mice were kept in standard cages No. 4, under conditions of unlimited access to water and food when natural changes in illumination. To test the toxic effect of the drugs was launched after a two-week quarantine of animals. The drugs were injected in a saline solution to warm-blooded animals orally into the stomach using an atraumatic tip. Monitor the effects of drugs had been produced for 14 days from the moment of introduction. As a control, were injected corresponding to the mass of the polymer compositions obtained without active substance, in equiano number of physiological solution.
Determination of the value of median lethal dose LD50(when n=7 for each of the tested doses, calculations were made according to the method of Litchfield and Wilcoxon signed ) showed that the value LD50for developed based drug rifampicin prolonged action of example 1 was 700 mg/kg, and for substance rifampicin 500 mg/kg Therefore, the average toxic dose for a new drug form of rifampicin was significantly higher (40%), and toxicity, respectively, lower than the original rifampicin.
Thus, the obtained nanoparticles means on the basis of rifampicin with prolonged action, exhibits high specific Akti the activity against Mycobacterium Tuberculosis with reduced toxicity compared to the original drug substance. This result allows us to conclude about the growth of therapeutic latitude and increasing therapeutic index when the reduction ratio of taking the drug due to prolongirovannomu his actions.
Developed a drug proposed for release in the form of enteric-soluble tablets or capsules.
Sources of information
1. Radar - encyclopedia of medicine / CH. edit Ufraw, 8th ed. M: "radar-2001", 2000. S-767.
2. Fang D., Singh M, O Hagan D., Hora M. Composition of microparticles and methods for their production // Patent RF №2257198 C2. - Publ. 27.07.2004,
3 Pandey R., Khuller G.. Oral nanoparticle-based antituberculosis drug delivery to the brain in an experimental model // Journal of Antimicrobial Chemotherapy 2006, V.57 (6). P.1146-1152.
4. Pandey, R., Sharma, A., Zahoor A. et al. Poly (DL-lactide-co-glycolide) nanoparticle-based inhalable sustained drug delivery system for experimental tuberculosis // Journal of Antimicrobial Chemotherapy 2003. V.52 (6). P.981-986.
5. Esmarili F., be started-Nasr M, Rad-Malekshahi M. et al. Preparation and antibacterial activity evaluation of rifampicin-loaded poly lactide-co-glycolide nanoparticles // Nanomedicine: Nanotechnology, Biology and Medicine 2007, V.3 (2).P. 161-167.
6. Ul-Ain Q., Sharma s, Khuller G.K. Chemotherapeutic Potential of Orally Administered Poly(Lactide-Co-Glycolide) Microparticles Containing Isoniazid, Rifampin and Pyrazinamide against Experimental Tuberculosis // Antimicrobial Agents and Chemotherapy 2003. V.47 (9). P.3005-3007.
7. Barrow E.L.W., Winchester G.A., Staas J.K. et al. Use of microsphere was Technology for Targeted Delivery of Rifampin to Mycobacterium tuberculosis-Infected Macrophages // Antimicrobial Agents and Chemotherapy 1998. V.42 (10). P.2682-2689.
8. Vranckx A., Demote M, Delaer M Headlight is aseptically composition, containing nanocapsules, and method thereof // Patent RF № 2145498 C1. - Publ. 20.02.2000,
9. Pharmaceutical technology: the technology of medicinal forms: Textbook for high schools / Under the editorship Cry and Gvieaway. Ed. 3-E. Rev. and ext. M.: Publishing house "Academy", 592 S.
10. Microencapsulation: Methods and Industrial Applications / Ed. S. Benita. 2nd ed. Taylor & Francis Group. 2006. 747 p.
11. Belenky, M. elements of a quantitative evaluation of the pharmacological effect / 2nd ed. revised and enlarged additional HP: Medgiz, 1963. S-106.
1. The drug prolonged action for the treatment of drug-resistant tuberculosis on the basis of rifampicin, characterized in that it is a stable nanoparticles and contains rifampicin, a biodegradable polylactic acid or a copolymer of lactic and glycolic acids, and surfactant, cryoprotector in the following ratio of components, wt.%:
|a biodegradable polylactic acid|
|or a copolymer of lactic and glycolic acids||20-60|
|surfactant and cryoprotector||rest|
2. Les is arctonoe tool according to claim 1, characterized in that the biodegradable polymer contains a polymer of lactic acid or a copolymer of lactic acid and glycolic acid or a copolymer of lactic and glycolic acid with a free carboxyl group.
3. The drug according to claim 1, characterized in that as a cryoprotectant contains D-mannitol or lactose, or glucose.
4. The drug according to claim 1, characterized in that as the surfactant contains polyvinyl alcohol or Polysorbate 80, or poloxamer 188, or serum albumin.
5. The drug according to claim 1, characterized in that represents the nanoparticles ranging in size from 250 to 500 nm.
6. The drug according to claim 1, characterized in that it is made in the form of tablets or capsules, or granules, or powder, or other oral forms.
SUBSTANCE: method of controlling light sensitivity of a laser radiation detector in the infrared range by exposing the detector to external fields, for a detector made from quantum wire based on InSb, doped with a donor-type impurity, with quantum wire diametre approximately equal to the value of the effective Bohr radius for an electron in the material of the quantum wire. The external effect is magnetic field with induction between 2 and 5 T.
EFFECT: broader light sensitivity of the laser radiation detector in the submillimetre wavelength range.
SUBSTANCE: in high-voltage electronic device containing high-voltage electrodes arranged in dielectric cover, on inner surface of cover in areas with high field intensity there is coating from composite material and polycrystalline material with volume conductivity of particles of 10-9 to 10-13 Ohm-1 cm-1 is used as its base; each of particles includes on its surface a nanolayer of binding nonorganic material; high-voltage electrodes are arranged in vacuum cover and fixed on insulators. Surface of dielectric cover, which is in vacuum, is covered with layer of material consisting of chrome, boron or zirconium oxides in the form of polycrystalline porous mass with particle sizes of 30 nm - 30 mcm, which are bound to each other with nonorganic material, for example silicon oxide (SiO2) with layer thickness of not more than 100 nm. Coating has thickness which is not less than 0.2 of length of free path of electrons in coating material at maximum value of working voltage of the device. Coefficient of secondary electron emission of the main coating material has value of not more than 1.5. High-voltage electrodes have modified surface having extra-fine crystalline or amorphous structure up to 30 mcm deep, for example by means of their processing with heavy-current pulse electron or ion beam. Device is placed into tight vessel filled with the medium with electric strength which is higher than air at atmospheric pressure, for example with transformer oil subject to cleaning and pumping in vacuum, or with sulphur hexafluoride (SF6). Vessel is filled with the above media under pressure higher than atmospheric.
EFFECT: increasing electric strength of devices, reducing their overall dimensions and weight.
7 cl, 3 dwg
SUBSTANCE: invention relates to medicine, namely, to experimental research in oncology and can be used in investigation of impact of metal nanoparticles on tumour growth in vivo. For this purpose, 0.2 ml of each: suspension of nanoparticles of metals of copper, zinc or alloy Cu+Zn+Fe in concentration 10 mcg/ml are introduced to tumour-carrying mice with sarcoma 180 three weeks after transplantation. Introduction is carried out 2 times per week during 5 weeks, after that introduction of metal nanoparticles is stopped.
EFFECT: method makes it possible to ensure increase of general and event-free duration of life of tumour-carrying mice with transplanted sarcoma 180 due to high ability of metal nanoparticles to penetrate into cells and imbed into various metabolic chains.
FIELD: process engineering.
SUBSTANCE: invention relates to polymer nanocomposites. Method of producing polymer composite with oriented mass of carbon nanotubes consisting of polymer matrix reinforced by oriented mass of carbon nanotubes comprises diluting polymer in solvent, forming nanocomposites layer on substrate by centrifuging it from polymer solution and thermally processing at temperature not exceeding polymer matrix destruction temperature. Filler represents vertically-oriented mass of carbon nanotubes grown on substrate. In forming nanocomposite layer on substrate by centrifuging, substrate is arranged perpendicular to centrifuge rotation plane.
EFFECT: producing polymer composite with oriented mass of carbon nanotubes with improved characteristics, simplified process.
SUBSTANCE: proposed nano radiator comprises 4-6 nm-dia nucleus of noble metal surrounded by two concentric envelopments. Envelopment nearest to nucleus represents an optically neutral organic layer with thickness of about 1 nm. Second 1-3 nm-thick envelopment is made up of J-aggregates of cyanine dyes. During electron excitation of metal nucleus plasmons, the latter actively interact with J-aggregate envelopment to excite cyanine dyes (Frenkel's excitons) and radiate light in visible range. Metal nucleus electrons may be excited by both photons and electrons.
EFFECT: high quantum output of luminescence and controlled spectrum of radiation in visible range.
3 cl, 1 dwg, 1 tbl
FIELD: process engineering.
SUBSTANCE: invention relates to hardening ad recovering machine parts by electric spark and may be used for part coating with magnetically conducting materials. Proposed electrode from alloying material is made up of nanocrystalline alloy 2-4 mm-wide 10-20 mm-long plates (80-100 pcs) screwed in hollow mandrel so that said plates extend beyond one end of the mandrel for 0.1-0.8 mm and, on the other end of mandrel, said plates jointed to washer and screw for connection with electric spark unit vibrator.
EFFECT: possibility to produce wear resistant reduced-brittleness coats that boast hardness of 10-15 GPa.
1 dwg, 1 tbl
SUBSTANCE: binder for preparing prepregs is a product of reacting polyamide acid and an epoxy-novolac oligomer with the following ratio of components in wt %: polyamide acid 1-20, epoxy-novolac oligomer - the rest. The invention also discloses a method of preparing the said binder and a prepreg from the said binder.
EFFECT: invention enables to obtain a product with homogeneous phase distribution of the polyimide component.
10 cl, 5 dwg, 2 tbl, 6 ex
SUBSTANCE: invention relates to chemistry and can be used to produce nanometric monodispersed and stable Mg(OH)2 and products obtained therefrom. The method involves mixing aqueous solution of a magnesium salt and aqueous solution of an alkali, stabilisation of the mixed product by adding a diluent, maturation of the stabilised product, cleaning the matured product to obtain magnesium hydroxide particles. The aqueous solution of the magnesium salt contains a surfactant which is ethoxylate, and an organic acid. The aqueous alkaline solution contains an alkali selected from a group comprising sodium hydroxide, potassium hydroxide and ammonium solutions, and a dispersing agent selected from polyacrylate acid type substances or salts thereof. The diluent which is used to stabilise the product of the mixture contains water and the same dispersing agent as the one used in the alkaline solution. The diluent is added with constant agitation during the stabilisation process. During the maturation step, the stabilised mixture of the product undergoes mechanical and chemical treatment using ultrasound which preferably lies between 20 and 45 kHz.
EFFECT: invention enables to obtain magnesium hydroxide nanoparticles in high concentrations and products therefrom.
15 cl, 5 dwg
SUBSTANCE: invention relates to agriculture, namely, to bee-keeping in part of combating bee diseases and their prevention. Proposed method to combat bee diseases using biocide properties of metal nanoparticles consists in giving stable bactericide and fungicide properties to beehives and their components, by using nanosize particles of metals in a composite material, from which the beehive is made.
EFFECT: invention provides for creation of medium inside a beehive that is destructive for wide spectrum of bee disease producing factors and remains stable for a long time, without negative impact at bees and humans.
2 cl, 1 ex
SUBSTANCE: in nanoelectronic semiconductor rectifying diode made of two contact areas produced from alloyed GaAs with concentration of Si 1×1018…1×1019 1/cm3, spacers made of GaAs, and heterostructure including three alternating areas: potential barriers made of AlyGa1-yAs, where y - molar share Al, with thickness from 1.70 to 8.48 nm with molar share Al from 0.4 and 1 and potential pit arranged between them with thickness of 7.91…12.44 nm, made of GaAs, ratio of thicknesses of layers of potential barriers is within the limits of 1.3…5 at appropriate ratio of molar shares Al, within the limits of 1.6…2.5.
EFFECT: development of a rectifying diode with shape BAX, making it possible to increase rectifier output voltage.
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to pharmaceutical field, and concerns a combined antituberculous pharmaceutical composition in a solid dosage form including a therapeutically effective amount of an active principle which is represented by a combination of sodium para-aminosalicylate and isoniazid, and pharmaceutically acceptable auxiliary substances, in the following proportions, wt % of total composition: sodium para-aminosalicylate - 36.8-90.41; isoniazid-1.08-3.38; auxiliary substances - the rest.
EFFECT: invention provides longer high blood serum concentration of active preparations, as well as prevents development of mycobacterium drug resistance to isoniazid.
4 cl, 8 tbl, 3 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to sulphonic 2-nitro-2-(3-aryl-1,2,4-oxadiazole-5-yl)ethane derivatives of formula I a-g la R=3-NO2C6H4, R1=NO2, R2=H; b R=3-NO2C6H4, R1=NO2, R2=CH3; c R=4-CH3OC6H4, R1=NO2, R2=H; d R=4-CH3OC6H4, R1=NO2, R2=CH3; e R=4-CH3OC6H4, R1=CO2Et, R2=H; f R=4-CH3OC6H4, R1=CO2Et, R2=CH3; g R=4-CH3C6H4, R1=CO2Et, R2=H.
EFFECT: preparation of the compound exhibiting antileprous and antituberculous activity.
1 cl, 1 tbl, 1 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to an antituberculous composition which can represent a solid dosage form containing a therapeutically effective amount of an active principle - a combination of sodium paraaminosalicylate (PAS) and zinc sulphate.
EFFECT: invention provides a synergetic effect which consists in higher antimycobacterial activity and enabled therapy of drug resistant forms of tuberculosis complicated by pulmonary tissue destruction.
9 cl, 1 ex
SUBSTANCE: in capsule, in accordance with the invention, at least, one hollow space is surrounded by wall. At least, part of wall includes polymer mixture, which contains, at least, one adsorbent. Polymer mixture contains, at least, thermoplastic material, preferably polyolefin, more preferably, polyethylene or polypropylene. Adsorbent is selected from group, consisting of silica gels, zeolites, alumosilicates, molecular sieves, active coal, oxides of alkali-earth metals, calcium sulfate. Capsule is intended for packing compositions for inhalation.
EFFECT: invention allows to prolong stability of medication compositions.
28 cl, 8 dwg
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention relates to chemical-pharmaceutical industry and medicine, in particular to composition, which possesses bacteriostatic and bactericidal action and is intended for treatment of tuberculosis diseases. Pharmacological composition with anti-tuberculosis action contains active substances - anti-tuberculosis medications (ethambutol, isoniazid, rifampicin, pirazinamide) and as potentiating agent of synergetic action, enhancing impact of chemical preparations, stabilised nanoparticles of silver.
EFFECT: invention possesses properties allowing to inhibit medication-resistant strains of tuberculosis mycobacteria.
5 ex, 1 tbl
SUBSTANCE: invention refers to medicine, particularly to phthisiology, and can be used in treating tuberculosis by antituberculous preparations (ATP). That is ensured by chemotherapy supplemented with daily introduction of the preparation taurin for at least 2 months.
EFFECT: method provides good tolerance to dosages of primary and reserve ATP required for therapy in various clinical forms of tuberculosis, reducing or eliminating various adverse reactions of therapy.
4 cl, 5 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention relates to prophylactic agent for skin, having antituberculous effect, which includes the following active substances - 0.50-0.75 wt % of streptomycin and 7.0-10.0 wt % of stabilised sol of silver nanoparticles, and also polyethylene oxides (PEO) of brands 400 and 1500 as the base.
EFFECT: invention provides a synergetic effect, which shows in ability to suppress antibiotic-resistant strains of microorganisms, including mycobacteria of tuberculosis, and in improvement of bactericide properties of proposed agent.
1 tbl, 5 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention relates to chemical-pharmaceutical industry, namely to creation of antituberculous composite medication, which contains isoniaside and individual glycoside of plant Stevia rebaudiana - stevioside or steviolbioside or mixture of said plant glycosides, which represent sweetener.
EFFECT: medication reduces toxicity of antituberculous medication isoniaside.
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention relates to chemical-pharmaceutical industry and medicine and deals with composition for treatment of different forms and locations of tuberculosis. Claimed composition consists of sodium aminosalicylate and polyvinylpyrrolidone with molecular weight 8000-60000.
EFFECT: composition possesses high bioavailability and reduced local-irritate action of sodium aminosalicylate.
3 ex, 1 tbl
SUBSTANCE: invention refers to new derivatives of dihydro-pyrroloquinoline of formula I where values of R1, R2, R3a and R3c radicals are specified in cl. 1 of the patent claim. Also the invention refers to a method for making the compound of formula I, to its application, a composite product based on the compound of formula I and a general antimicrobial agent and a pharmaceutical composition based on the compound of formula I.
EFFECT: there are prepared new derivatives of dihydro-pyrroloquinoline exhibiting antibacterial activity.
26 cl, 4 dwg, 11 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention relates to field of medicine and deals with composition, which contains virus-like particle (VLP) and amyloid-beta peptide. Substance of invention includes application of construction, which consists of virus-like particle (VLP) structure, which is chemically stitched with fragment of Aβ-1-42 peptide and its pharmaceutically acceptable salt for preparation of pharmaceutical composition, intended for treatment of dementia in patient by introduction of construction in dose 5-1000 mcg subcutaneously, every 4-8 weeks. Invention also includes combination, which includes construction on item 1, and at least, one agent, selected from group of medications, traditionally applied for treatment of Alzheimer's disease.
EFFECT: reduction of side effects.
16 cl, 6 ex