Medicament with prolonged anti-calcium activity in the form of 1/10% intravenous solution
FIELD: pharmaceutical chemistry.
SUBSTANCE: invention, in particular, relates to prolonged therapeutical form of domestic slow calcium channel blocker, namely ankardin-retard-AZIn (active principle 7,7-ethylenedioxybenzopyran-2,2-dione) in the form of 0.1% solution administered in dose 1 ml in the form of complex with poly(ethylene oxide) 400. Pre-clinical investigations indicated that Ankardin-retard-AZIn was a sufficiently active calcium ion antagonist and, after clinical investigations, it could be applied in medical practice for prevention and treatment of cardiovascular diseases.
EFFECT: extended choice of drugs.
6 tbl, 4 ex
The invention relates to medicine and pharmacy, namely to pharmacotherapy of disorders of the cardiovascular system, and the development of new anti-ischemic tool ankerdine-retard AZIn in the form of a 0.1% solution for intravenous possessing prolonged anticalcium action.
In medical practice a number of anti-ischemic drugs with short and prolonged anticalcium activity: phenoptin, nifedipine, diltiazem, senzit, difril (Mashkovsky PPM Medicines. - 2000. 1. - s-415), as well as the newly developed drugs are short-range diamancel-forte (Abishev AS, Agayev AM, Borisenko O.V. Patent of Russia 2187303 C1) and ankerdine-retard AZT (Abishev AS, Agayev AM Patent of Russia 2219927 C1).
However, the above calcium antagonists have a high incidence of side effects, such as phenoptin to 10%, and nifedipine 30%, manifested in the form of swelling of the legs, hypotension, changes in heart rate, hyperglycemia, headache, dizziness, fatigue, flushing of the skin (Mashkovsky PPM Medicines. - 2000. 1. - s, 301, 185). In addition, in recent years, noted that the use of short acting dihydropyridines, especially nifedipine, may increase the risk of developing a malignant tumor is, myocardial infarction and death in patients with arterial hypertension (Kuleshov EV calcium Antagonists and their role in the treatment of diseases of the cardiovascular system. - 2002. - part 1 and 2; Furberg .D., Psaty B.M, Meyer J.V. Circulation. - 1995. - V.92. - R-1331; Psaty V. M., Heckbert S.R., T.D. Koepsell et al. JAMA. - 1995. - V.274. - P.620-625; Pahor m, Psaty B.M., M.H. Alderman et al. Lancet. - 2000. - Dec.9. - 356 (9246):1970-4). In animal experiments has also been established embryotoxicity of diltiazem and most of the calcium antagonists 1,4-dihydropyridine. When long-term therapy with diltiazem, nifedipine and felodipina in the early stages of pregnancy are documented cases of intrauterine fetal death and abnormalities of skeletal development in infants. Therefore, diltiazem and all of 1,4-dihydropyridine derivatives of the first and second generation contraindicated in any pregnancy (Svensson A. Clin. Exp. Hypertension. - 1993. - V.15. - R-1361; Lowe S.A., RubinP. C.J. Hypertension. - 1992. - V.10. - P.201-207).
As for new antagonists of calcium diamancel-forte and ankerdine-retard-AZT, although they are the most active, than their counterparts, and do not have the above-mentioned side effects, but the first is virtually insoluble in aqueous media and therefore slowly permeates through the membrane (within 2 hours) and circulates in the blood line not more than 8 hours, while the second exhibits a consistent prolonged action for 26 hours and the maximum concentration in PLA is IU the blood is only 1.5 hours.
In connection with the above, the development of a new calcium antagonist in the form of a solution for intravenous administration in emergency cases and with prolonged action is urgent because, despite the small number, the list of indications for their use is expanding: arterial hypertension, chronic coronary insufficiency, cardiac arrhythmias, neurological, psychiatric practice and other
The closest to the physico-chemical and pharmacological properties of the claimed product is of ankerdine-retard AZT (Abishev AS, Agayev AM Patent of Russia 2219927 C1).
Therefore, the aim of the present invention is to develop a new drug is an antagonist of calcium ions (ankerdine-retard-AZIn) in the form of a 0.1% solution for intravenous administration in emergency cases, in which the active ingredient is the same 7,7’-ethylenediaminetetra-2,2’-dione.
This goal is achieved by the synthesis of a new combined connection ankerdine-retard-AZIn, representing a complex of 7,7’-ethylenediaminetetra-2,2’-dione with polyethylene oxide with average molecular weight of 400 (REO-400), widely used in pharmaceutical practice, to obtain water-soluble hydrophobic drugs.
To astasia time to declare connection technology for producing the dosage form in the form of a 0.1% solution of 1 ml (ankerdine-retard-AZIn), in which, as described above, as the active component contains 0.001 g substance diamancel. For the specified dosage forms studied technological and pharmacological parameters.
The invention is illustrated by the following specific examples of pre-clinical and technological research:
Example 1. The technology of obtaining injectable form ankerdine-retard-AZIn.
In a glass reactor with a capacity of 3 l is placed a portion pulverized powder substance diamancel and the required number of REO-400. The mixture with constant stirring warm for 3 hours at a temperature of 100°C. Then, with constant stirring, add the required amount of injection water with a temperature close to 100°C. Then, the solution cooled to room temperature under aseptic conditions and filtered through a paper filter.
The resulting solution was poured into ampoules of 1 ml, sealed, check on their tightness, sterilized for 1 hour at a temperature of 105°With control on the mechanical inclusion, labeled and Packed into containers.
For this technology is received and tested 5 batches of product that meets the requirements of the global Fund XI publications (see table 1).
Example 2. The trial of antiarrhythmic activity of various dosage forms of diamancel on chloralkali model arrhythmia.
the La setting antiarrhythmic actions of various forms of diamancel study preventive activity on the model of ventricular fibrillation, caused by the method Malinow et al. (Malinow, M., F. Battle, Malamud Century Nervous mechanisms in ventricular arrhythmias by calcium chloride in rats. Circulat. Res., 1953. - Vol.I. - N-6. - p.554-559).
For this group of laboratory animals (rats 8 individuals) administered study drugs (diamancel-forte, ankerdine-retard-AZT and ankerdine-retard-AZIn of 0.1% at 1 ml) in a dose of 1 mg/kg For testing tablets two groups of rats (8 animals each) enter suspension of diamancel-forte and ankerdine-retard-AZT prepared in 0.9% sodium chloride solution with the addition of Tween-80), as well as ankerdine-retard-AZIn in the same dose. Rats control series injected solvent, animal group comparison - suspension substance diamancel prepared in 0.9% sodium chloride solution with the addition of Tween-80, at the same dose. After exposure (see. table 2) all animals injected intravenously 10% solution of calcium chloride at a dose of 300 mg/kg and spend the ECG recording in the second standard lead. See the development of ventricular fibrillation. Take into account the frequency of implementation of arrhythmias, the frequency of sinus rhythm, the duration of the arrhythmia, the frequency of death. Parameters duration of arrhythmias assessed by student's criterion, the frequency of implementation of arrhythmia, sinus rhythm, and death by Chi - square. The results of the experiments are shown in table 2.
As follows from table 2, diamancel significantly reduces the frequency of death alive is different from adults, in this case, the implementation of arrhythmia reliably manifests the property of the drug to restore sinus rhythm. The differences between the different dosage forms domuncula and substance of all of the parameters are statistically insignificant, however, significantly (p<0,05) different from the control series at exposure of 2.5 hours between the introduction, in particular diamancel-forte, ankerdine-retard (AZT and AZIn) and aritmogeni (frequency vosstanavlivaya normal rhythm and the ability to prevent the death of animals). This shows comparable activity of these dosage forms domuncula and its substance. If you increase the exposure up to 26 hours of the dosage forms listed only ankerdine-retard (AZT and AZIn) retains its effect to the same extent, whereas substance and diamancel-fbrte not active. Therefore, ankerdine-retard (AZT and AZIn) comparable activity with the substance and dimensiom-forte, but significantly exceeds their duration of action, the latter of ankerdine-retard-AZIn comes almost immediately after the introduction (within 5-10 min), which is also evident from the data on comparative pharmacokinetic studies of various dosage forms of nifedipine and domuncula (see tables 3 and 4). Thus, it can be noted that the objective has been achieved.
Example 3. Test protivojishemical the activity of various medicinal forms of diamancel on the model of occlusion of a coronary artery.
To establish anti-ischemic effect of different dosage forms domuncula studied preventive activity in a model of acute coronary occlusion caused by ligation of the anterior branch of the left coronary artery in the middle third method Nversatio (Marrucina NV On the experimental reproduction in rabbits myocardial infarction and arrhythmias (Cardiology. - 1972. No. 12. - S-111).
For this group of laboratory animals (rats 8 individuals) administered the test drugs (diamancel-forte, ankerdine-retard-AZT and ankerdine-retard-AZIn 0.1% solution 1 ml) in a dose of 1 mg/kg For testing tablets two groups of rats (8 animals each) enter suspension of diamancel-forte and ankerdine-retard-AZT prepared in 0.9% sodium chloride solution with the addition of Tween-80, and ankerdine-retard-AZIn in the same dose. Rats control series injected solvent, animal group comparison - suspension substance diamancel prepared in 0.9% sodium chloride solution with the addition of Tween-80, at the same dose. After exposure (see table 5) in all animals cause occlusion of the coronary artery and spend the ECG recording in the second standard lead. See the development of signs of myocardial ischemia: decreased R-wave voltage, expressed recovery interval ST (cat's hump”). Take into account the severity of signs of ischemia in % (R-wave - to the original level, the interval ST - UB is Nude). The parameters of the severity of ischemia assessed by student's criterion. The results of the experiments are given in table 5.
As follows from table 5, when the exposure 2.5 h all legform diamancel, and after 20 h only ankerdine-retard (AZT and AZIn) significantly (p<0,05) compared to the control prevents the decrease of the voltage of the R-wave (11-16%) and the rise of the ST segment (16-22%), indicating that the anti-ischemic effect of the study drug. Differences between sectorname diamancel at exposure of 2.5 h, and between the effects ankerdine-retard (AZT and AZIn) when both exposures are statistically insignificant, this allows to conclude about the comparable activity of all legform diamancel at exposure of 2.5 h, and ankerdine-retard (AZT and AZIn) (2.5 and 20 h). With increasing exposure to 20 h the severity of ischemia on the background of substance and diamancel-forte becomes indistinguishable from that in the control series, whereas ankerdine-retard (AZT and AZIn) exerts anti-ischemic properties in the same way as and when the exposure of 2.5 hours This indicates significantly longer compared to the rest of sectorname diamancel anti-ischemic effect ankerdine-retard (AZT and AZIn). Therefore, ankerdine-retard (AZT and AZIn) and diamancel-forte comparable activity with the substance of diamancel, however ankerdine-retard (AZT and AZIn) significantly exceeds that of other dosage forms and the substantive is in duration of action.
Example 4. Test deprimating activity of various dosage forms of diamancel in the test potentiation subthreshold dose of sodium thiopental.
To establish the duration of action of various dosage forms of diamancel study potentiation of drug action subthreshold dose (12 mg/kg, I/V) sodium thiopental (Rajewski HP Pharmacology of neuroleptics. - M, - 1976., 271 (C).
For this group of laboratory animals (rats 8 individuals) to introduce the study drug (diamancel-forte, ankerdine-retard-AZT and ankerdine-retard-AZIn 0.1% solution 1 ml) in a dose of 1 mg/kg For testing tablets two groups of rats (8 animals each) enter suspension of diamancel-forte and ankerdine-retard AZT, prepared in 0.9% sodium chloride solution with the addition of Tween-80), as well as ankerdine-retard-AZIn in the same dose. Rats control series injected solvent, animal group comparison - suspension substance diamancel prepared in 0.9% sodium chloride solution with the addition of Tween-80, at the same dose. After exposure (see table. 6) all animals in the/type in a freshly prepared solution of sodium thiopental (12 mg/kg). See the development of the lateral position of the animal. The frequency of occurrence of lateral position estimate by Chi-square. The results of the experiments are shown in table 6.
As follows from table 6, all forms of diamancel demonstrate the ability in order to potentiate narcotic effect of sodium thiopental at exposure of 2 hours between administration of the drug and the test agent. The drug entered all lekforma, shows comparable activity, a statistically significant relative to control, but not distinguished between the different dosage forms of the drug. When exposure 18 h between the introduction of diamancel and sodium thiopental activity diamancel-forte, ankerdine-retard and substance did not differ from control. However ankerdine-retard-AZT retained its activity at the level of the other forms on exposure 2 hours.
Thus, diamancel-forte, ankerdine-retard-AZT and substance of diamancel comparable in activity, however, ankerdine-retard-AZT compared to other sectorname and substance has a greater duration. However, if you consider that the content of the active component in ankerdine-retard-AZIn significantly less (20 times)than in ankerdine-retard-AZT and on all tests of its validity is almost at the level of the latter, the prospects of applying ankerdine-retard-AZIn in emergency cases, the treatment of arterial hypertension and ischemic heart disease as antianginal means more preferable. In addition, as can be seen from the pharmacokinetic data presented in tables 3 and 4, the maximum concentration ankerdine-retard-AZT in plasma is reached in 1.5 hours after taking the drug, whereas a similar concentration at ankerdine-retard-AZIn is istihaada almost immediately after the introduction within 5-10 minutes
As a result of preclinical pharmacodynamic (see tables 2, 5 and 6) and pharmacokinetic (see tables 3 and 4) studies have shown that ankerdine-retard (AZT and AZIn) has prolonged high activity and good bioavailability.
Comparative activity of different dosage forms of diamancel influence on model chloralkali arrhythmia.
|№ p/p||Substance||Exposure time, h||Frequency implementation arrhythmia %||The frequency of sinus rhythm, %||The duration of the arrhythmia||The frequency of mortality, %|
|6||The substance of diamancel||26||100,0||0,0||42,2±4,3||100,0|
|* p< 0.05 compared with the control series|
The main pharmacokinetic characteristics retarding forms of nifedipine (“C”) and Dimanche (“AZT”).
|Drugs||Cmaxng/ml||Tmaxhour||AUC ng/ml * h||X/And %|
|X/A is the relative bioavailability compared to the drug “S”|
The parameters characterizing the prolonged action retarding dosage forms of nifedipine (“b” and “C”) and Dimanche (“AZT” and “AZIn”).
|Drugs||MRT, h||HV, ng/ml||HVD, h|
The data presented in tables 3 and 4, which were obtained by graphical and mathematical modeling. The maximum concentration of the drugmaxthe relative time of occurrence of Tmaxand the area under the curve of concentration-time (AUC), as in the case of nifedipine (U.S. Patent 4,880,623) were calculated for the FCP is full of curves
Comparative activity of different dosage forms of diamancel influence on the model of coronary occlusion.
|№ p/p||Substance||Exposure time, h||The voltage of the R-wave (% of initial level)||The degree of ST elevation (% to control)|
|6.||The substance of diamancel||2,5||57,0*||82,2*|
|7.||The substance of diamancel||20||45,9||99,0|
|* p<0.05 compared with the control series|
Comparative activity of different dosage forms of diamancel influence on narcotic effect of sodium thiopental.
|№ p/p||Substance||Exposure time, h||The frequency of occurrence of lateral position, %|
|7.||The substance of diamancel||2||62,5*|
|8.||The substance of diamancel||18||12,5|
|* p<0.05 compared with the control series|
The tool prolonged anticarcinoma steps, characterized in that a represents a 0.1% solution of 1 ml for intravenous administration containing as an active ingredient 0.001 g of 7,7-ethylenediaminetetra-2,2-dione in the form of a complex with polyethylene oxide of molecular weight 400.
FIELD: medicine, cardiology.
SUBSTANCE: the present innovation deals with decreasing side effects of medicinal preparation of cardiotoxic component. For this purpose it is suggested to apply cariporide to decrease unfavorable impact of macrolide antibiotic, rulide, in particular. The innovation suggested provides the chance to remove side effects of macrolide antibiotic regarding patient's heart under conditions of ischemia and reperfusion.
EFFECT: higher efficiency of application.
FIELD: organic chemistry, pharmaceutical compositions.
SUBSTANCE: invention relates to substituted 3-oxo-1,2,3,4-tetrahydroxinoxalines of general formula 1 , wherein R1 represents substituted sulfanyl or substituted sulfonyl group, containing as substituent optionally substituted C1-C4-alkyl, optionally substituted C3-C8-cycloalkyl, aryl-(C1-C4)alkyl optionally substituted in aril or alkyl group, heterocyclyl-(C1-C4)alkyl optionally substituted in heterocycle or alkyl group; R2 and R3 independently represent hydrogen, halogen, CN, NO2, optionally substituted hydroxyl, optionally substituted amino group, optionally substituted carboxylic group, optionally substituted carbamoyl group, optionally substituted arylcarbonyl group or optionally substituted heterocyclylcarbonyl group; R4 and R5 independently represent hydrogen or inert substituent. Claimed compounds are high effective kaspase-3 inhibitors and are useful in production of pharmaceutical compositions for treatment of diseases associated with excess apoptosis activation, as well as for experimental investigations of apoptosis in vivo and in vitro. Also disclosed are pharmaceutical composition in form of tablets, capsules or injections in pharmaceutically acceptable package, as well as method for production thereof and therapy method.
EFFECT: pharmaceutical composition for apoptosis treatment and investigation.
6 cl, 3 dwg, 8 ex, 1 tbl
SUBSTANCE: method involves using mononuclear autologic marrow fraction containing 6-9x104 mesenchyma cells per 1 ml or autologic mesenchyma trunk cells. The cells are separated from brain bioptate in the amount of 106 cells/kg of patient body mass. The preparations are intracoronarily introduced in fractions at a rate of 3-5 ml/min into the right coronary artery. The introduction is also carried out in intra-arterial mode in jets or in drops.
EFFECT: higher survival rate and life quality of cardiologic patients.
FIELD: new 2,4,6-trimethyl-3-oxypyridine nitrosuccinate and method for production thereof.
SUBSTANCE: claimed compound is useful in medicine as future antiishemic agent with vasodilatation effect and has potent protective action in barotraumatic damages and ballistic wounds due to inhibition of secondary necrosis creation and progress. Compound of present invention is obtained by nitration of malic acid with mixture of sulfuric and nitric acids, separation of nitrohydroxymalic acid and treatment thereof with 2,4,6-trimethyl-3-oxypyridine in alcohol media with subsequent isolation of target product.
EFFECT: new antiishemic agent.
2 cl, 1 ex
SUBSTANCE: the present innovation deals with phospholipid complexes of proanthocyanidine A2 and pharmaceutical compositions upon their basis as antiatherosclerotic agents, those for preventing and treating myocardial and cerebral infarction. Phospholipids of the above-mentioned complex should be preferably chosen out of lecithins, phosphatidyl choline, phosphatidyl ethanolamine, phosphatidyl serine. The innovation provides the preparation to treat the above-mentioned diseases due to decreasing the quantity and burden of atheromatous plaque, decreased obstruction of carotid arteries and decreased thickness of vascular walls.
EFFECT: higher efficiency of prophylaxis and therapy.
9 cl, 11 dwg, 6 ex, 2 tbl
FIELD: organic chemistry, biochemistry, medicine, pharmacy.
SUBSTANCE: invention relates to new aminobenzophenones of the formula (I):
or their pharmaceutically acceptable salts. These compounds elicit properties of inhibitors of cytokines secretion, in particular, 1β-interleukin (IL-1β) and tumor necrosis α-factor (TNF-α) and to secretion of polymorphonuclear superoxide that are useful for treatment of inflammatory diseases, for example, skin diseases, such as psoriasis, atopic dermatitis. In the formula (I) R1 is taken among the group consisting of halogen atom, hydroxy-, mercapto-group, trifluoromethyl, amino-group, (C1-C3)-alkyl, (C2-C3)-olefinic group, (C1-C3)-alkoxy-, (C1-C3)-alkylthio-, (C1-C6)-alkylamino-group, (C1-C3)-alkoxycarbonyl, cyano-group, carbamoyl, phenyl or nitro-group under condition that when R1 means a single substitute then it at ortho-position, and when R1 means more one substitute then at least one substitute of R1 is at ortho-position; R2 means one substitute at ortho-position being indicated substitute is taken among the group consisting of (C1-C3)-alkyl, (C1-C3)-alkoxy-group; R3 means hydrogen, halogen atom, hydroxy-, mercapto-group, trifluoromethyl, amino-group, (C1-C3)-alkyl, (C2-C3)-olefinic group, (C1-C3)-alkoxy-, (C1-C3)-alkylthio-, (C1-C6)-alkylamino-group, (C1-C3)-alkoxycarbonyl, phenyl, cyano-, carboxy-group or carbamoyl; R4 means hydrogen atom or (C1-C3)-alkyl; Q means a bond or -SO2-; Y means (C1-C15)-alkyl, (C3-C10)-carbocyclic group or phenyl being each of them can be substituted optionally with one or some similar or different substitutes designated by the formula R5; R5 means halogen atom, (C1-C4)-alkyl, amino-, (C1-C3)-alkoxy-group, (C1-C3)-alkoxycarbonyl or -COOH; X means oxygen or sulfur atom. Also, invention relates to a pharmaceutical composition and to a method for treatment and/or prophylaxis of inflammatory diseases.
EFFECT: valuable medicinal properties of compounds and composition.
9 cl, 2 sch, 2 tbl, 29 ex
FIELD: organic chemistry, medicine, pharmacy.
SUBSTANCE: invention relates to new 1-(p-thienylbenzyl)-imidazoles of the formula (I): , wherein indicated residues represent the following values: R(1) means halogen atom, (C1-C4)-alkoxyl, (C1-C8)-alkoxyl wherein one carbon atom can be replaced with heteroatom oxygen atom (O); R(2) means CHO; R(3) means aryl; R(4) means hydrogen halogen atom; X means oxygen atom; Y means oxygen atom or -NH-; R(5) means (C1-C6)-alkyl; R(6) means (C1-C5)-alkyl in their any stereoisomeric forms and their mixtures taken in any ratios, and their physiologically acceptable salts. Compounds are strong agonists of angiotensin-(1-7) receptors and therefore they can be used as a drug for treatment and prophylaxis of arterial hypertension, heart hypertrophy, cardiac insufficiency, coronary diseases such as stenocardia, heart infarction, vascular restenosis after angioplasty, cardiomyopathy, endothelial dysfunction or endothelial injures, for example, as result of atherosclerosis processes, or in diabetes mellitus, and arterial and venous thrombosis also. Invention describes a pharmaceutical composition based on above said compounds and a method for their applying also.
EFFECT: valuable medicinal properties of compounds and composition.
10 cl, 19 ex
FIELD: medicine, pharmacology, pharmacy, medicinal biochemistry.
SUBSTANCE: invention proposes a pharmaceutical composition that comprises, in particular, N-(1-octyl-5-carboxymethyl-dimethylindolin-7-yl)-2,2-dimethylpropaneamid or its pharmacologically acceptable salts as inhibitor of enzyme ACAT and inhibitor of HMG-CoA-reductase that represents pravastatin, lovastatin, simvaststin, fluvastatin, rivastatin, atorvastatin, rosuvastatin or pitavastatin used as active component of the composition. The combination of active substances shows the expressed synergistic effect. Invention provides enhancing activity of the composition in clinical applying.
EFFECT: valuable medicinal properties of composition.
71 cl, 2 tbl, 3 ex
FIELD: organic chemistry, medicine, pharmacy.
SUBSTANCE: invention relates to a group of new derivatives of 4,5-dihydro-1H-pyrazole of the general formula (I):
wherein R means phenyl, thienyl or pyridyl and these indicated groups can be substituted with (C1-C3)-alkoxy-group or halogen atom; R1 means phenyl that can be substituted with (C1-C3)-alkoxy-group or pyridyl group; R2 means hydrogen atom or hydroxy-group; Aa means one group among the following groups: (i) , (ii) , (iii) , (iv) or (v) ; R4 and R5 mean independently from one another hydrogen atom or (C1-C8)-branched or unbranched alkyl; or R4 means acetamido- or dimethylamino-group or 2,2,2-trifluoroethyl, or phenyl, or pyridyl under condition that R5 means hydrogen atom; R6 means hydrogen atom at (C1-C3)-unbranched alkyl; Bb means sulfonyl or carbonyl; R3 means benzyl, phenyl or pyridyl that can be substituted with 1, 2 or 3 substitutes Y that can be similar or different and taken among the group including (C1-C3)-alkyl or (C1-C3)-alkoxy-group, halogen atom, trifluoromethyl; or R3 means naphthyl, and its racemates, mixtures of diastereomers and individual stereoisomers and as well as E-isomers, Z-isomers and mixture of E/Z-compounds of the formula (I) wherein A has values (i) or (ii), and its salt. These compounds are power antagonists of Cannbis-1 (CB1) receptor and can be used for treatment of psychiatric and neurological diseases. Except for, invention relates to a pharmaceutical composition used for treatment of some diseases mediated by CB1-receptor, to a method for preparing this composition, a method for preparing representatives of compounds of the formula (I) wherein Aa means group of the formulae (i) or (ii), intermediate compounds used for preparing compounds of the formula (I) and to a method for treatment of some diseases mediated by CB1-receptor.
EFFECT: valuable medicinal properties of compounds.
16 cl, 9 ex
SUBSTANCE: method involves administering Noliprelum in postoperative period for reducing left ventricle hypertrophy.
EFFECT: enhanced effectiveness of treatment in early postoperative period.
FIELD: medicine, pharmacy.
SUBSTANCE: treatment involves using the injection solution based on water-soluble prednisolon formulation containing sodium salt and accessory additive. Prednisolon sodium phosphate is used as prednisolon water-soluble formulation, and anhydrous sodium hydrogen phosphate and sodium dihydrogen phosphate dihydrate taken in the ratio = (1.375-1.5):1, respectively, are used as sodium salt, and propylene glycol is used as an additional additive in the following ratio of components, wt.-%: prednisolon sodium phosphate (as measured for prednisolon), 2.5-3.5; anhydrous sodium hydrogen phosphate, 0.045-0.055; sodium dihydrogen phosphate dihydrate, 0.03-0.04; propylene glycol, 12-17, and injection water, the balance, up to 100%. Invention can be used in producing hormonal preparation prednisolon in injection formulation for treatment of rheumatism, infectious nonspecific polyarthritis, bronchial asthma, leukemia and other diseases. Invention provides enhancing stability of prednisolon-containing solution and prolonged storage time.
EFFECT: improved and valuable properties of solution.
3 tbl, 2 ex
FIELD: medicine, pharmacology, pharmacy.
SUBSTANCE: invention relates to the injection solution based on nalbuphine hydrochloride eliciting the expressed analgesic effect, and to a method for its preparing. The injection solution comprises the following components, wt.-%: nalbuphine hydrochloride, 0.8-2.2; buffer mixture, 0.5-3.5; stabilizing agent, 0.15-0.25; Trilon B (chelating component), 0.001-0.2, and water, the balance. Invention provides preparing the domestic preparation with analgesic effect and stability for above 2.5 years.
EFFECT: improved and valuable medicinal properties of solution.
11 cl, 1 tbl, 5 ex
FIELD: pharmaceutical industry.
SUBSTANCE: composition contains cellulose derivatives, glycosaminoglycanes, oligosaccharides, novocain or mercain (both as local anestetics), non-steroidal anti-inflammatory agent, adrenalin, glycerol, and purified water at specified proportions of components.
EFFECT: achieved protection of cornea against mechanical damage due to prevented access of air bubbles and blood under lens, best visualization of fundus of eye, and reduced operation time.
FIELD: pharmaceutical industry.
SUBSTANCE: pharmaceutical form contains (i) peptides with aggregation tendency in the form of their salts: acetates, gluconates, glucuronates, lactates, citrates, benzoates, or phosphates, which are dissolved of dispersed, and (ii) acids corresponding to above-listed salts.
EFFECT: lowered aggregation tendency and improved release of active substance resulting in improved bioavailability of peptide active substances.
22 cl, 9 tbl, 3 ex
SUBSTANCE: after keeping during pharmaceutically acceptable period oxaliplatinum is placed in transparent, colorless and residue-free solution at concentration of, at least, 7 mg/ml, and a solvent contains sufficient quantity of, at least, one hydroxylated derivative chosen among of 1.2-propandiol, glycerol, maltite, saccharose and inositol. The innovation describes the way to obtain such a preparation. The preparation is stable during pharmaceutically acceptable period of time, that is it remains transparent, colorless and free of any residue within the range of 2-30 C that could be available during its transportation, storage and/or any handling.
EFFECT: higher efficiency of application.
14 cl, 6 ex, 4 tbl
SUBSTANCE: the suggested disinfectant contains glutaric aldehyde, didecyldimethylammonium chloride, ethoxylated alcohol, propylene glycol and water at certain ratios. The method to treat objects, those of medicinal indications, among them, deals with treating an object with the above-mentioned disinfectant followed by keeping disinfectant on the object during the time and at temperature to provide disinfection and/or sterilization of the object followed by washing disinfectant off. The present innovation provides hermetic nature of elements and connective elements of flexible and rigid endoscopes, soldered and glued sites in the course of disinfection.
EFFECT: higher efficiency of application.
10 cl, 3 ex
SUBSTANCE: the present innovation deals with cryoprotective preparations that contain recombinant interferon-α2. The suggested cryoprotective preparation contains recombinant interferon-α2, polyethylene glycol 3000-6000, polyglucin, buffered 0.02%-Trilon B solution at pH being 5.5-7.0 and glycerol at certain ratio of components per 1.0 g preparation. The suggested cryoprotective preparation can additionally contain glycine, 3,7-bis(dimethylamino)phenothiazonium chloride, dry immunoglobulin preparation or dry immunoglobulin preparation for enteral intake. The present innovation provides maximal keeping the activity of recombinant interferon-α2 in cryoprotective preparation at multiple alteration of positive and negative environmental temperature and during storing this cryoprotective preparation under these conditions.
EFFECT: higher efficiency of application.
4 cl, 8 ex
FIELD: veterinary science.
SUBSTANCE: the suggested preparation is being the solution of either avermectines or their derivatives in organic solvents or their mixtures at concentration of 1-35 g/100 ml; as organic solvents the preparation contains benzyl alcohol, ethanol, triethylene glycol, dimethylsulfoxide or their mixtures. This preparation provides in case of needle-free injection the development of "depot" of active substance. Moreover, the latter practically does not enter milk, so the preparation could be applied for treating lactating cows.
EFFECT: higher efficiency of needle-free injection technique.
1 cl, 2 dwg, 3 tbl
FIELD: chemico-pharmaceutical industry.
SUBSTANCE: the present innovation deals with new stabilized pharmaceutical composition in its lyophilized form including the compound of formula I
as an active ingredient and lactose disaccharide as a stabilizing agent. The present pharmaceutical compositions are of high stability at storage. As for active ingredient it is not destroyed in the course of time.
EFFECT: higher efficiency.
10 cl, 15 ex, 6 tbl
SUBSTANCE: preparation comprises echinocandine substance of formula I or its pharmaceutically permissible salt, pharmaceutically permissible micelle-forming surface-active agent and non-toxic aqueous solvent and stabilizing agent.
EFFECT: improved stability and bioaccessibility properties.
48 cl, 4 tbl
FIELD: pharmacology, fluorinated quinolone-based drug, in particular ofloxacine for injections.
SUBSTANCE: claimed composition contains therapeutically acceptable amount of ofloxacine and trilon-B, sodium chloride, water for injections as additives.
EFFECT: high therapeutic effectiveness; non-crystallized active agent for a long-time storage.