Agent for bacterial infections treatment
SUBSTANCE: agent contains Rifabutin sorbated in polymeric nanoparticles matrix, potassium cholesterylphosphate, or sodium glycocholate, or hexadecyl dihydrogen phosphate, or a-tocopheryl succinate, water-soluble polymeric stabiliser and bulking agents. Polymeric nanoparticles sized 100-800 nm include lactic acid polymer/polymers and/or lactic and glycolic acid copolymer/copolymers at glycolic acid content in specified copolymers up to 50 mole %. Molecular weight of specified polymers and copolymers is 5 to 300 kDa. Molecular weight of water-soluble polymeric stabiliser is no more than 70 kDa and is selected from the group including polyvinyl alcohol, polyvinylpyrrolidone, polysorbate and seralbumin.
EFFECT: new agent provides durable action of Rifabutin; higher bioavailability of Rifabutin and efficiency of bacterial infection treatment.
3 dwg, 1 tbl, 7 ex
The invention relates to the field of medicine and pharmacology, specifically to medicines for treatment of bacterial infections, especially tuberculosis and diseases of the gastrointestinal tract.
In recent years there has been a significant increase in the incidence of tuberculosis in all countries of the world, which is associated with emergence of resistant strains and the spread of diseases of the immune system, including AIDS. According to who estimates, in the period up to 2020 the number of people newly infected with TB will reach 1 billion, 200 million people will get sick, and 35 million will die from TB if not will be found new, more effective treatments.
Low efficiency used to date anti-TB drugs due to the fact that the growing number of patients with multidrug resistance caused by the emergence of drug-resistant strains of microorganisms that require the use of new drugs with a broad antimicrobial spectrum.
In the context of a sharp deterioration of the epidemiological situation on tuberculosis, one of the priorities of tuberculosis is increasing the efficiency of chemotherapy of tuberculosis. The main objectives and tasks of chemotherapy are, first, the recovery of the patient with dimensionality his usual lifestyles by preventing fatal and spread of TB to other members of society, and secondly, in preventing the development of drug-resistant strains of Mycobacterium tuberculosis, which significantly complicates the subsequent treatment.
Difficulties in the treatment of severe forms of TB, as well as characteristics of the causative agent of the disease require long-term use of several anti-TB drugs in different doses and with different frequency. The complexity of compliance with such a regimen is obvious, at the same time, irregular drug intake is associated with a high risk of resistance development.
The situation is similar with chronic diseases of the gastrointestinal tract caused by bacteria Helicobacter species, especially Helicobacter pylori (peptic ulcer disease, gastritis, colitis, proctitis, etc). According to who estimates, approximately 50% of the population are infected with these bacteria. The difficulties of therapy of this infection is also caused by the development of resistance.
The most significant of the possible ways to improve the efficiency of antibacterial drugs is the development of drugs for the long gradual selection of antibiotic that will reduce the applied dose and/or to simplify the treatment regimen.
Known drugs of directed action, in which the medicinal substance is chemically linked to the macromolecular nose is Telem. An example of this approach is a covalent conjugate of isoniazid and dextran (RF Patent No. 2143900 "Way to get isoniazid prolonged action", CL AC 31/455, publ. 10.01.2000). The disadvantage of these drugs is low capacity (ratio: drug - carrier), as well as the complexity of the technology of their creation.
Closest to the proposed invention is an antibacterial agent for the treatment of pulmonary infections by RF patent No. 2185818, CL AC 9/08, publ. 27.07.2002, which is the composition of medicinal substances adsorbed on the particles polyalkylacrylate (C2-C10or their mixtures, the size of 200-700 nm, containing the dextran with a molecular mass of 20-70 kDa and fillers in the following ratio, wt.%:
|Polyalkylacrylate (or their mixture)||20-40|
|The medicinal substance||1-10|
The composition may further contain a solvent in an amount of not more than 98 wt.% the total weight of the colloidal system, and can optionally contain surface-active substances (surfactants) (poloxamer, poloxamine, Polysorbate and others) to whom icesto not more than 20 wt.% of the total weight of the aqueous colloidal systems.
Known antibacterial intravenously provides intracellular localization of drugs in alveolar macrophages in effective therapy for the quantities, but it has some significant drawbacks. Firstly, the main advantage of a known drug - delivery of drugs to macrophages using nanoparticles is realized only when intravenous nanoparticle dosage forms. At the same time in the treatment of both tuberculosis and diseases of the gastrointestinal tract, Helicobacter pylori, it is the oral route of administration of drugs is a priority. However, polyalkylacrylate, which is the basis of the polymer matrix of known medicines, differ very high rate of decomposition in a living organism, which does not allow to achieve long-term excretion of the drug from the polymer matrix, especially when administered orally. Secondly, some bacterial infections, including Mycobacterium tuberculosis and Helicobacter pylori, are characterized by significant extracellular populations of pathogens. This applies in particular to the bacteria Helicobacter pylori, which have the ability to inhibit phagocytosis. It is clear that a well-known tool, the main advantage of which is due to the ability of nanoparticles to deliver drugs prophetic is tion in macrophages, in this case, it may be ineffective and will not provide the maximum manifestation of the inherent medicinal substance positive characteristics. Thirdly, polyalkylacrylate must be synthesized from the corresponding monomers, and obtaining particles of a certain size (less than one micron) in the course of the synthesis is a complex technological problem, resulting in a lack of stability characteristics of the resulting nanoparticles, which have an adverse effect on the sorption properties of the polymer carrier.
The task of the claimed invention is to provide means prolonged action for the treatment of bacterial infections on the basis of biodegradable and biocompatible polymers, which will provide the maximum manifestation of the inherent medicinal substance positive characteristics and will increase the effectiveness of the treatment.
The solution of this problem is achieved by the proposed tool is based on rifabutin, adsorbed nanoparticles inside the polymer carrier, which are used as nanoparticles the size of 100-800 nm polymer/polymers of lactic acid and/or copolymer/copolymer of lactic and glycolic acids content of glycolic acid in said copolymer of 50 mole%, the molecular weight of these polymers, the copolymer is from 5 to 300 kDa. The tool may further comprise cholesterylester potassium, or glycocholate sodium, or hexadecyl dihydrophosphate, or α-tocopherylacetate as a hydrophobic counterion for amino rifabutin, water-soluble natural or synthetic polymer stabilizer with a molecular mass of 70 kDa selected from the group comprising polyvinyl alcohol, polyvinylpyrrolidone, Polysorbate or serum albumin, and fillers, in the following ratio, wt.%:
|The specified polymeric media||10-50|
or glycocholate sodium, or hexadecyl
|dihydrophosphate, or α-tocopherylacetate||0,01-10|
|The specified polymer stabilizer||5-40|
As fillers in the proposed tool can be used sugar with cryoprotective properties (for example, glucose, lactose, mannitol, trehalose), and salts (e.g. sodium chloride, sodium citrate).
When choosing a drug beginning to offer tools, be aware that most is in TB patients have multi-drug resistance, therefore the most common in practice, the treatment of tuberculosis antibiotics will not be able to provide high efficiency of treatment.
Rifabutin is a semisynthetic broad-spectrum antibiotic, effective against intracellular and extracellular located microorganisms. The indications for the use of rifabutin are chronic multidrug-resistant tuberculosis caused by rifampicin-resistant strains of Mycobacterium tuberculosis (in combination therapy), as well as infections caused by Mycobacterium tuberculosis, Mycobacterium avium, Mycobacterium xenopi, and other atypical mycobacteria (eg, patients with immunodeficiency). Rifabutin is also effective against strains of Helicobacter pylori resistant to the main drug prescribed for the treatment of this infection: amoxicillin, clarithromycin, metronidazole and tetracycline.
The choice of the polymer carrier was determined by the chemical properties of rifabutin and the task. The best sorption properties showed homopolymers of lactic acid and copolymers of lactic and glycolic acids, including additional content of terminal carboxyl groups, which increases the effectiveness of the inclusion of rifabutin in the polymer matrix of the nanoparticles.
In addition, the relative content of rifabutin in finished dosage form), the public is improved by reducing the content of the polymer carrier and auxiliary substances; the useful properties of the nanoparticles (high sorption rifabutin, size, aggregation stability) are stored.
Due to sorption of the antibiotic inside the nanoparticles from biodegradable polymer increases its bioavailability.
The proposed tool was prepared as follows.
The known method of manufacture of a simple emulsion water/oil by single or multiple homogenization of the organic and aqueous phase, containing the components of the funds, with subsequent evaporation of the organic solvent receive nanoparticles from homopolymers of lactic acid, or copolymers of lactic and glycolic acids by size of 100-800 nm. Sorption of rifabutin nanoparticles inside polymer is carried out in the process of formation of a suspension of the nanoparticles in the removal of organic solvent from the emulsion. To increase the content of active ingredient (rifabutin) in the finished dosage form is introduced an additional step consisting in concentrating nanosuspension method of centrifugation or ultrafiltration and allowing to reduce the content of auxiliary substances (stabilizer).
The invention is illustrated by the following examples.
Example 1 (control). Obtaining nanoparticles by the method of simple emulsions
System consisting of 2-20% solution of the polymer/polymers mo is full of acid and/or copolymer/copolymer of lactic and glycolic acids, and 0.5-6% solution of rifabutin in an organic solvent (usually methylene chloride, chloroform or ethyl acetate) and 0.5-5% aqueous polymeric emulsion stabilizer (volume ratio of organic and aqueous phase 1:5), homogenized to obtain the emulsion. Organic solvent from the resulting emulsion is removed by evaporation at normal pressure and room temperature (stirring for 3 hours) or under reduced pressure using a rotary evaporator. The resulting nanosuspension filter add 0-10% filler-cryoprotectant (e.g., glucose, lactose, mannitol, trehalose) and lyophilizers. The average particle size is 100-800 nm depending on conditions of homogenization and used stabilizer for emulsions and surfactants. The degree of inclusion of rifabutin is 60-80%. The average particle size is 100-800 nm (depending on the conditions of homogenization and used stabilizer emulsion).
Example 2. Obtaining nanoparticles by the method of simple emulsions (initial concentration)
System consisting of 2-20% solution of the polymer/polymers of lactic acid and/or copolymer/copolymer of lactic and glycolic acids, and 0.5-5% solution of rifabutin in an organic solvent (usually methylene chloride, chloroform or ethyl acetate) and 0.5-5% aqueous polymeric emulsion stabilizer (volume ratio of organic and aqueous phase 1:5), homogenized to receive the Oia emulsion. Organic solvent from the resulting emulsion is removed by evaporation at normal pressure and room temperature (stirring for 3 hours) or under reduced pressure using a rotary evaporator. Then, the resulting nanosuspension filtered and centrifuged within 30 to 90 minutes at 4000 rpm to remove Supernatant, the precipitate redispersion in water, add 0-10% filler-cryoprotectant (e.g., glucose, lactose, mannitol, trehalose) and lyophilizers. The average particle size is 100-800 nm depending on conditions of homogenization and used stabilizer emulsion (surfactant). The degree of inclusion of rifabutin is 60-80%. The average particle size is 100-800 nm (depending on the conditions of homogenization and used stabilizer emulsion).
Example 3. Obtaining nanoparticles by the method of simple emulsions with hydrophobic counterion)
System consisting of 2-20% solution of the polymer/polymers of lactic acid and/or copolymer/copolymer of lactic and glycolic acid, 0.5-5% solution of rifabutin and 0.005-1% cholesterylester potassium, or glycocholate sodium, or hexadecyltrichlorosilane, or α-tocopherylacetate in an organic solvent (usually methylene chloride or chloroform) and 0.5-5% aqueous polymeric emulsion stabilizer (volume ratio of organic and aqueous phase :5), homogenize to obtain the emulsion. Organic solvent from the resulting emulsion is removed by evaporation under reduced pressure using a rotary evaporator. Then, the resulting nanosuspension filtered and centrifuged within 30 to 90 minutes at 4000 rpm to remove Supernatant, the precipitate redispersion in water, add 0-10% filler-cryoprotectant (e.g., glucose, lactose, mannitol, trehalose) and lyophilizers. The average particle size is 100-800 nm depending on conditions of homogenization and used stabilizer emulsion (surfactant). The degree of inclusion of rifabutin is 70-98%. The average particle size is 100-800 nm (depending on the conditions of homogenization and used stabilizer emulsion).
Obtained in accordance with examples 1, 2, 3 advanced powder is mixed with auxiliary substances, ensuring the manufacturability of the process of capsule filling, and filled in hard gelatin capsules, including gastro-resistant hard capsules.
As a further auxiliary substances the following substances (per 100 weight. parts of medicinal substance, adsorbed nanoparticles inside the polymer carrier comprising additives target):
|Microcrystalline cellulose is||0-30|
|Colloidal silicon dioxide||0-20|
|Sodium lauryl sulfate||0-15|
Before filling hard gelatin capsules composition can be formed into pellets, coated with a polymer shell, contributing to prolonged selection of medicinal substance and consisting, for example, of polymers Eudragit E-100 (methacrylic acid copolymer) and Kollicoat SR 30 D (30% aqueous dispersion based on polyvinyl acetate) with appropriate additives (for example, triethylcitrate, talc, simeticone emulsion).
The compositions of the claimed antibacterial agents obtained in examples 2 or 3, in wt.%:
Composition 1 (example 2)
|PLA, MM 300 kDa, the average particle size of 600 nm||10|
Composition 2 (example 2)
|PLGA-COOH, MM 18 kDa, average particle size 200 nm||28,5|
|Polyvinyl alcohol, MM 30-70 kDa||14,3|
|PLGA (50:50), MM 2500 kDa, Sredni a particle size of 300 nm||25|
|Serum albumin, MM 6-10 kDa||25,4|
Part 4 (example 3)
|PLGA, MM 20 kDa, the average particle size of 220 nm||40,0|
|Polyvinyl alcohol, M.M. 30-70 kDa||4,5|
Example 4. The study of the kinetics of excretion of rifabutin from nanoparticles
The experiment was carried out in an environment simulating gastric juice (water, pH of 1.2, 37° (C)used the received structure 2. Nanoparticle rifabutin, obtained from 1 ml of the reaction mixture, resuspendable in 1 ml PBS buffer solution (pH 7.4) and quantitatively transferred into plastic tubes containing 24 ml of an aqueous solution of hydrochloric acid (pH of 1.2), containing 0.1% ascorbic acid. The tubes were incubated in a thermostatted shaker (37°C, 230 rpm). Sample volume of 500 ál were collected at specified time intervals (immediately after dilution, 30 min, 1, 2, 4 and 6 h), the nanoparticles were separated by ultrafiltration using a membrane microfilters (Microcon 30 kDa (Millipore, USA). The concentration of free (not bound to the nanoparticles) rifabutin was determined spectrophotometrically.
As shown by the results of the experiment (figure 1), the proposed composition of the nanoparticles provide a slow release of rifabutin in an environment simulating the gastric juice.
Example 5. The biodistribution of the proposed antibacterial agents when administered orally to rabbits.
Rabbits were injected oral nanoparticle form rifabutin (composition 3). As control was used a standard substance rifabutin. The drugs were injected in the form of gelatin capsules. The animals took blood samples after 5 min, 1, 3, 5, 15 and 24 h and determined the concentration of rifabutin by HPLC method.
As can be seen from figure 2, the use of nanoparticles allows to significantly increase the concentration of rifabutin plasma and the integral value (area under the curve of plasma concentration - time), which amounted to 276 mg/ml×h for substance rifabutin and 507 μg/ml×h for its nanoparticle form. Thus, nanoparticle form oral introduction provides increased bioavailability of rifabutin almost in 2 times.
Example 6. Increased effectiveness of the proposed dosage form of rifabutin in the treatment of EC the pilot tuberculosis in mice
Research chemotherapeutic activity of rifabutin associated with polymeric nanoparticles, was conducted in mice with experimental tuberculosis. Female mice of BALB/c (age 7-8 weeks) were infected by the intravenous injection of Mycobacterium tuberculosis H37Rv at a dose of 5×106-107colony forming units (CFU) per mouse. Infected mice were divided into three groups (n=10) and introduced them to standard oral drug rifabutin (RB) and nanoparticle rifabutin (RB/PLGA) (part 3) on the fourth, fifth and sixth day after infection. The drugs were injected at the same dose of 20 mg/kg as a control was used animals not receiving treatment (Control).
A day after completing the course the 3-day therapy of infected animals were subjected to euthanasia, in aseptic conditions were isolated and homogenized lung (right), then spent the seeding of the Cup with the environment N. The count of live mycobacteria in units of CFU was performed 3-4 weeks. The results are shown in figure 3.
As can be seen from figure 3, in experimental tuberculosis in mice nanoparticle drug (RB/PLGA) has higher antibacterial effect compared to the standard substance (RB), that is, improves the efficiency of treatment.
Example 7. Increased effectiveness of the proposed dosage form of rifabutin in the treatment expertise is mental Helicobacter pylori infection in mice
Research chemotherapeutic activity of rifabutin associated with polymeric nanoparticles were performed on mice with experimental Helicobacter pylori infection.
To infect the female mice of BALB/c (age 7-8 weeks) were injected through a tube into the stomach 100 μl of a suspension of bacteria N. pylori (strain SS1) in the dose of 5×106-107colony forming units (CFU) per mouse. One week after infection, infected mice were divided into three groups (n=10) and introduced them to standard oral drug rifabutin (RB) and nanoparticle rifabutin (RB/PLGA) at a dose of 20 mg/kg / day for 7 days. As control was used animals not receiving treatment (Control).
A day after completing the course the 7-day treatment, animals were subjected to euthanasia, in aseptic conditions were isolated and homogenized stomach, then spent plating on plates with agar. The count of live mycobacteria in units of CFU was performed after 10 days. The results are shown in table 1.
As can be seen from table 1, in experimental tuberculosis in mice nanoparticle drug (RB/PLG) has higher antibacterial effect compared to the standard substance (RB), that is, improves the efficiency of treatment.
Thus, the results show that due to the nanoparticle nature and affinity floor the dimensional matrix of the nanoparticles to the gastric mucosa offer antibacterial provides increased bioavailability of rifabutin, resulting in increased efficiency of treatment of infections, in particular Mycobacterium tuberculosis, and Helicobacter pylori. The increased bioavailability reduces the dose of the antibiotic and, therefore, reduces toxic side effects.
In addition, the present invention is a dosage form for oral administration, and also avoids the technologically complex and time-consuming process of synthesis of the polymer matrix of strings.
|Therapeutic effectiveness of dosage forms of rifabutin in the treatment of experimental infection with N. pylori in mice|
|Group||Log10 CFU N. pylori/I 00 mg tissue/mouse ±SD|
|Negative control (intact animals)||0|
|Positive control (infected animals without treatment)||4.09 to±0,26|
The treatment for bacterial infections on the basis of rifabutin, adsorbed in the matrix polymer nanoparticles, including fillers, characterized in that the polymer carrier contains nanoparticles of the size of 100-800 nm polymer/polymer is in lactic acid and/or copolymer/copolymer of lactic and glycolic acids content of glycolic acid in said copolymer of 50 mol.%, molecular weight of these polymers and copolymers ranges from 5 to 300 kDa, and the tool further comprises cholesterylester potassium, or glycocholate sodium, or hexadecyl dihydrophosphate, or α-tocopherylacetate, and water-soluble natural or synthetic polymer stabilizer with a molecular mass of 70 kDa selected from the group comprising polyvinyl alcohol, polyvinylpyrrolidone, Polysorbate and serum albumin in the following ratio, wt.%:
|The specified polymeric media||10-50|
|Cholesterylester potassium, or glycocholate|
|sodium, or hexadecyl dihydrophosphate,|
|The specified polymer stabilizer||5-40|
FIELD: medicine; pharmacology.
SUBSTANCE: composition displays tuberculostatic activity in respect of isoniazid-resistant M. Tuberculosis and amplifies specific pharmacological effect of isoniazid and ethambuthol hydrochloride due to its synergism. The composition is made in the form of granules with the components in the following quantities, g: isoniazid - 0.3000, ethambuthol hydrochloride - 0.3000, pectin - 0.3000.
EFFECT: high tuberculostatic activity; low toxicity and reduced side effects of the components.
2 cl, 4 tbl
SUBSTANCE: invention refers to medicine, specifically to phthisiology, and can be used for pulmonary tuberculosis treatment. For this purpose antibacterial treatment according is applied according to standard modes. In addition 5% unithiol solution in amount 5 ml per 200 ml of 0.9% sodium chloride solution is introduced intravenously. Unithiol introduction is alternated to contrical in amount 10 th.unit per 200 ml of 0.9% sodium chloride solution is introduced intravenously for the next day. Treatment course is 10 injections of each preparation. Invention widens range of pulmonary tuberculosis treatment, improving treatment efficiency due to reduction of abacillation time and degradation cavity closure, prevention of by-effects reactions of antitubercular preparations, removal of tubercular intoxication symptoms.
EFFECT: development of effective method of pulmonary tuberculosis treatment.
3 tbl, 2 ex
SUBSTANCE: invention refers to medicine, phthisiology. Antibacterial therapy is carried out under standard conditions. From first day of treatment transcoetaneous analgesic electric stimulator of nerves is applied at frequency 77 Hz. Points 4 GI, 5 TR, 6 MC, 14 VG and also pulmonary frontal projection are exposed by posterior midline, right and left paravertebral lines. Total exposure is 30-35 minutes. Treatment course is 20 sessions. Method reduces abacillation time and destruction cavity closure time.
EFFECT: reduced abacillation time and destruction cavity closure time.
2 ex, 2 tbl
FIELD: medicine; pharmacology.
SUBSTANCE: invention refers to medicinal agents containing combined inhibitor of dipeptidylpeptidase IV (DPPIV) and biguanide agent. Offered application of pharmaceutical agent implies production of preventive and therapeutic agent and method of intensified effects of active circulating GLP-1 and/or active circulating GLP-2. Besides, invention concerns method of prevention or treatment of disease connected with active circulating GLP-1 and/or active circulating GLP-2, specifically diabetes, obesity, hyperlipidemia, gastrointestinal diseases. Combined inhibitor DPPIV of formula (I) and biguanide agent, specifically phenformine, methformin or buformine stimulates action of active circulating glucagon-like peptide-1 (GLP-1) and/or active circulating glucagon-like peptide -2 (GLP-2) and, therefore inhibits destruction of GLP-1 and GLP-2, with their levels raised up with biguanide agent.
EFFECT: agent has improved efficiency.
17 cl, 12 tbl, 425 ex
FIELD: medicine; pharmacology.
SUBSTANCE: to produce composition of common agent, substance or combination of substances, copolymer of lactic and glycolic acid, polysorbate 80 and dimethyl sulfoxide taken in specified ratio are heated at 50÷60°C and mixed to produce homogeneous transparent liquid, which is cooled to room temperature and watered. Produced suspension containing nanoparticles sized 200-400 nm is used according to its intended purpose.
EFFECT: provided technologically available production method of medicinal agents of new generation based on common high-performance and almost non-toxic substances.
4 cl, 4 ex, 5 tbl, 1 dwg
SUBSTANCE: antibacterial therapy is conducted in accordance to standard conditions. 1 tablet vobenzim TID 30 minutes before a meal, is included into the complex treatment of pulmonary tuberculosis starting from the first day. Also, the daily transcutaneous electroneurostimulation (TENS) is performed in direct pulmonary plane above the area of pathologic focus and in the central universal zone - along the median line, right and left paravertebral lines, at comfort energetic mode with frequency 77 Hz, total exposure time 30-35 min and 20 sessions of treatment course.
EFFECT: method improves a microcirculation in body organs and tissues, provides the anti-inflammatory and analgesic effect, increases the immune response and resistance to infectious agents, normalizes the balance and enhances the production of endorphins, cortisone, dopamine, provides the spasmolytic and anti-edema action.
2 tbl, 2 ex
FIELD: medicine; pharmacology.
SUBSTANCE: medicine for treatment of tuberculosis, contains the 30% alcoholic tincture of medicinal plants: knotgrass (Polygonum aviculare) herb, garden violet (Viola tricolor) herb, aspen (populus tremula) rind, agrimony (Agrimonia) herb, agrimony (Agrimonia) roots, rough-fruited cinquefoil (Potentilla recta) herb, golden thoroughwax (Bupleurum) herb, medic hop (Medicago lupulina) cone, Adonis vernalis herb, late red bartsia (Odontites vulgaris) herb, Betula leaf, bird cherry (Prunus padus) tree rind, common peony (Paeonia officinalis) root, common burdock (Arctium lappa) roots, foxtail clover (Trifolium rubens) bloom, cowberry (Comarum palustre) roots, Inula root, wheat grass (Agropyron) root, garden angelica (Angelica officinalis) root, coltsfoot herb, snowdrop anemone (Anemone sylvestris) herb, snowdrop anemone (Anemone sylvestris) root, locoweed semilunar (Astragalus) herb, arborescent aloe (Arborescence aloe) succus, swallowwort (Chelidonium majus) herb, black current (Ribes nigrum) leaf, garlic (Allium sativum) bulb, greater burnet (Sanguisorba officinalis) root, lady's finger (Lathyrus pratensis) herb, dandelion (Taraxacum officinale) root, stringing nettle (Urtica dioica) herb, common origanum (Origanum vulgare) herb, ginger plant (Tanacetum vulgare) herb, bottle brush (Equisetum arvense) herb, common wormwood (Artemisia absinthium) herb, crystal tea ledum (Ledum palustre) herb, common juniper (Juniperus communis) needle, parnassia herb, mother-of-thyme herb, flat-leaved snakeroot (Eryngium) herb, shinleaf (Ramischia secunda) herb, willow herb root and field pennycress (Thlaspi arvense) herb taken in specific proportion and added by 3 volume percent of 10% propolis tincture.
EFFECT: tincture shows efficiency in treating tuberculosis.
FIELD: medicine, phthisiology.
SUBSTANCE: it is necessary to introduce ipratropium bromide per 2 dosages at 6 a.m., 5 p.m. and 11 p.m. The innovation enables to change the mode of introducing chinolytics at taking into account the onset of the greatest bronchial obstruction during 24 h.
EFFECT: higher efficiency of therapy.
SUBSTANCE: method involves carrying out antibacterial therapy in standard mode. Wobenzyme and homeopathic drugs are additionally introduced into treatment course. Wobenzyme is given at a dose of 1 pill thrice a day 30 min before taking meals. Homeopathic drugs like Apis mellifika 6 China officinalis 6, Chelidonium mayus 6, Stannum 6, Sanguinaria Canadensis 6, Callium bronchicum 6, Carbo vegetabilis 6 are given at a dose of 5 grains thrice a day irrespective of food intake daily during the whole treatment course.
EFFECT: enhanced effectiveness of treatment; reduced risk of adverse side effects.
FIELD: medicine, pharmacology, pharmaceutical technology, pharmacy.
SUBSTANCE: invention relates to a new generation of antibacterial preparations based on D-cycloserine that comprises nanoparticles and possessing the regulated effect. Method for preparing this preparation involves heating an agent containing a mixture consisting of D-cycloserine, PLGA 50/50, D-mannitol, polysorbate-80 and dimethylsulfoxide taken in the definite ratio at temperature 50-60oC to obtain uniform clear liquid followed by its cooling to room temperature, dilution with water, and formed suspension containing nanoparticles of size 3.0 ± 0.5 nM (˜20% of the total amount of particles) and ˜200 nM (˜80% of the total amount of particles) are used by designation. Invention provides preparing the preparation possessing high antibacterial activity, prolonged effect, relative harmless and low toxicity.
EFFECT: improved preparing method, improved and valuable medicinal properties of agent.
3 cl, 4 tbl, 5 ex
FIELD: medicine; veterinary science.
SUBSTANCE: preparation consists of viral-bacterial polyvalent blood serum for diarrhea with antibody titre 1:300-1:600 and sodium hypochlorite solution concentrated 300-350 mg/l at ratio of serum: sodium hypochlorite 7:3. Additionally contains serum maral blood preparation in ratio 2:1, where 2 portions are serum maral blood preparation. Method implies that preparation is injected in dosage 4 ml preventively. Therapeutically preparation is injected intramuscularly in dose 4-5 ml per 10 kg 2 or 3 times every 48 or 48, 72 hours respectively.
EFFECT: medical product and application method allow for lowered consumption of hyperimmune serum while preserving high medical preventive efficiency.
4 cl, 4 tbl, 1 ex
FIELD: medicine; dermatovenerology.
SUBSTANCE: daily before each injection of benzylpenicillin sodium salt a patient gets intravenously within 15 minutes osmotic diuretic mannitol in the dosage 2 g/kg of patient's body weight. In 30 minutes after its completion they administer intravenously 12 million units of benzylpenicillin sodium salt, the course of treatment is 10 days. At this penetration of benzylpenicillin to the arachnoid cavity increases in the conditions of temporary osmotic burst of the hematoencephalic barrier by means of mannitol effect, also sanitation of the nervous system is provided.
EFFECT: method allows to increase efficiency of the specific therapy of advanced neurosyphilis; to minimise side effects; is easy in production and is widely available in hospitals.
4 tbl, 2 ex
SUBSTANCE: invention concerns topica of antimicrobic action for infected dermhelminthiasis and blennosis treatment. The declared antimicrobial agent contains compounding of fluoroquinolones group, metronidazole, 0.05-0.2% solution of chlorhexidine bigluconate and organosilicone glycerohydrigel with the composition Si(C3H7O3)4·xC3H8O3·yH2O, where 3≤x≤10, 20≤y≤40 as the basis. As antibacterial agent of fluoroquinolones group, it contains pefloxacine or ofloxacine or cyprofloxacine or norfloxacine or lomefloxacine or levofloxacine or moxifloxacine orsparfloxacine or enoxacine. The agent has broad spectrum of application, strong therapeutic impact and doesn't have frank side effects. The agent is characterised by strength, convinient storage and administration.
EFFECT: creation of effective antimicrobial agent.
2 cl, 11 ex, 1 tbl, 2 dwg
SUBSTANCE: invention was targeted at obtaining crystals of acetonitrile solvate of 6-fluor-1-methyl-7-[4-(5-methyl-2-oxo-1,3-dioxolene-4-yl)methyl-1-piperazinyl]-4-oxo-4H-[1,3]thiazeto[3,2-a]quinoline-3-carboxylic acid (compound B), which is an intermediate compound in obtaining crystals of 6-fluor-1-methyl-7-[4-(5-methyl-2-oxo-1,3-dioxolene-4-yl)methyl-1-piperazinyl]-4-oxo-4H-[1,3]thiazeto[3,2-a]quinoline-3-carboxylic acid of III type (compound A). Compound B crystals are mostly precipitated by regulation of super-saturation during crystallisation involving acetonitrile as a solvent. Then compound A crystals of III type are obtained crystal desolvation.
EFFECT: increased efficiency of compounds.
6 cl, 4 dwg, 4 tbl, 4 ex
SUBSTANCE: group of inventions concerns medicine and can be applied in treatment of bacterial infections caused by gram-positive bacteria. The methods involve administration of dalbavancin for treatment of bacterial infections, particularly of gram-positive bacterial infections of skin and soft tissues. Dosage schemes include administration of dalbavancin once a week, which would sustain therapeutic drug level in plasma for at least 1 week. The claimed pharmaceutical compositions include single dalbavancin dose sufficient for sustaining therapeutically effective level of dalbavancin in plasma.
EFFECT: prolonged therapeutic effect against gram-positive bacterial infection.
86 cl, 13 dwg, 17 tbl, 10 ex
FIELD: medicine; urology.
SUBSTANCE: method includes making a diagnosis, allocating originators from the primary and secondary centres of patient's infection, and, after definition , using cultural method, of their sensitivity to the most effective etiotropic preparation, injecting it to a patient. After taking the blood from the patient, separating it into plasma, suspension erythrocytes and phagocytes by means of consecutive rotation with the rate of 2100 rpm for 10 minutes, cooling them preliminary to the temperature of +5°C, the method further includes deleting toxic blood plasma and replacing, in peer quantity, with Ringer solution and, with the suspension of erythrocytes entered into this solution, driply parenterally injecting in a vascular bed of a patient. The suspension of phagocytes, after being irradiated with emission of helium-neon laser of λ=0.63 mcm for 10-15 minutes power to 15 MW, is saturated with a solution of etiotropic ofloxacin preparation in a dose of 400 mg and, being sustained for 30 minutes, the solution obtained is injected parenterally intravenously to a patient. Nifuratel is injected perorally to a patient in a dose of 400 mg. A course comprises 12 procedures daily.
EFFECT: raised efficiency of treatment; reduced terms of treatment and decreased by-effects.
SUBSTANCE: essence of the invention lies in a composition which, after introduction to an individual, is capable of inducing a humoral immune response at the given individual the humoral immune response performing bactericidal effect against two or three of supervirulent rows of generations A4, ET5 and a number of generations of the 3rd serogroup in N.meningitidis. of an external membrane. Five albuminous antigens are used, i.e. (1) protein "NadA"; (2) protein "741"; (3) protein "936"; (4) protein of "953" and (5) protein "287".
EFFECT: development of a vaccine against two or more rows of supervirulent meningococcus generations.
29 cl, 1 tbl
SUBSTANCE: invention is intended for preventive treatment of nosocomial peritonitis in patients with already developed peritonitis, after applying laparostomy. Stage-by-stage sanation of an abdominal cavity is performed introducing at each sanation, 400 ml of a preparation of bacteriophage active against a potential originator of nosocomial peritonitis. Daily, before putting off laparostomy, 2 times a day 200 ml of the same preparation of bacteriophage is introduced into a gastroenteric tract, at a colon lesion it is introduced through a probe, at a lesion of the top department of a gastroenteric tract through rectum. Additionally, kypherone rectally to all patients in the quantity of 1 suppository 2-3 times a day for 5-10 days.
EFFECT: effective preventive treatment of nosocomial peritonitis due to complex etipathogenic influences on development of infectious process.
1 tbl, 4 ex
SUBSTANCE: invention relates to production of bis(4-alkylaminopyridine-1) alkanes of formula I where R1 -s linear or branched alkyl, cycloalkyl or arylalkyl groups having from 4 to 18 carbons, preferably from 8 to 12 carbons, ideally - normal octyl, R2 - linear or branched alkylene groups having from 4 to 18 carbons, preferably from 8 to 14 carbons, ideally - 1,10 decandyl, X1, X2 - halogenanions (identical or diverse): fluoride-, chloride-, bromide-, iodideanions, ideally - chlorideanions through interreacting of 4-alkylaminopyridine of formula II with disubstituted alkylene of formula III X1-R2-X2 in a solvent at increased temperature with mole ratio of formula II compound to formula III compound equals 2:1, the process is carried out in anoxic environment, acetic acid or its mixture with water is used as a solvent, meanwhile the compound of formula II is treated with the compound of formula III in gradual and continuous way or portionwise, ensuring the reaction at temperature ranging from 90° to 130°C, ideally from 100 to 105°C.
EFFECT: preparation of bis(4-alkylaminopyridine-1) alkanes of high quality with higher yield at essential saving of expandable materials.
6 cl, 8 ex
FIELD: medicine; pharmacology.
SUBSTANCE: invention claims application of starches substituted by quarterly ammonium groups with substitution degree of 0.4 to 3.0 with the help of a linker, in infection diseases treatment. Suppression of 1 type herpes virus replication by the claimed starches is demonstrated, in comparison to zero antivirus effect of non-modified starches. Minimal inhibiting concentration for staphylococci and mycobacteria is 5-60 g/l.
EFFECT: efficient infection disease treatment by the claimed starches.
5 cl, 7 tbl
SUBSTANCE: invention concerns coordination complex of platinum (II) diaminocyclohexane with block copolymer containing structure of the general formula PEG-block-poly(carbo), where PEG is a poly(ethyleneglycol) segment, and carbo is a repeating chain containing carboxylic group in the side chain, and platinum (II) diaminocyclohexane is immobilised by block copolymer due to linkage between carboxylic carbo residue anion and platinum; as well as method of obtaining the complex and anticancer composition including effective anticancer quantity of coordination complex and pharmaceutically acceptable carrier. In addition, invention concerns coordination complex of platinum (II) diaminocyclohexane and block copolymer with structure of the general formula (1-a) or (2-a) , where R1 is a hydrogen atom or unsubstituted or substituted serial or furcated C1-C12 alkyl group, L1 and L2 are linkage group, R3 is a hydrogen atom, protective group of aminogroup, hydrophobic group or polymerisation-capable group, R4 is hydroxylic group or initiator residue, each of R5 radicals is independently a hydrogen atom, alkali metal ion or protective group of carboxylic group, m is an integer from 5 to 20000, n is an integer from 2 to 5000 if alkali metal ion comprises 50% or more of the number of R5 groups which is n, with platinum (II) diaminocyclohexane immobilised by the said block copolymer due to linkage between carboxylic carbo residue anion and platinum, and equivalent ratio of diaminocyclohexane platinum (Pt) to carboxylic groups of the said block copolymer (Pt/COO-) is 0.3-1. The invention also concerns the method of obtaining this coordination complex and method of tumour treatment involving introduction of effective quantity of combined coordination complex of platinum (II) diaminocyclohexane and coordination complex of cis-platinum to a patient.
EFFECT: increased composition efficiency.
20 cl, 2 ex, 1 tbl