Means for warning of the consequences and complications of induced ischemia of the heart
(57) Abstract:The invention relates to medicine, particularly cardiology, and can be used for the treatment and prevention of the consequences and complications of ischemia and reperfusion injury of the heart. To achieve this goal apply timogen dose to 3.58-to 1.79 mg/kg intravenously before-induced ischemia. The drug significantly reduced the likelihood of consequences and complications due to ischemia and reperfusion of the heart, contributed to the recovery of cardiac function. 6 Il. The invention relates to medicine, primarily to cardiology, and can be used to prevent ischemic and postischemic heart damage in humans. It is known that cardiovascular diseases are on the first place among the causes of mortality, with the principal cause of mortality in cardiac patients with coronary heart disease (CHD) and its complications.Known drug timogen used in the clinic as an immunomodulator. It does not affect the immune system of healthy individuals does not cause toxic reactions in a dose of 10,000 times therapeutic, has no chronic toxicity. When it is oricheskogo Committee of the USSR Ministry of health to medical application dated January 13, 1989/. L. 1989, C. 10). The authors examined the antiischemic properties of the drug, allowing you to use it for a new purpose.Currently there are many different drugs used for the prevention and treatment of coronary heart disease.However, they all have significant side effects.The purpose of the invention is the prevention of complications and consequences of ischemia and repartie heart without side effects.To achieve this goal was to use the drug timogen dose 7,15 µg/kg, This dose was the most effective in the treatment of cardiac arrhythmias, and, as you know, the arrhythmia is one of the most dangerous complications of ischemic heart disease.The invention is illustrated in Fig. 1-6.Example 1. A control series of 8 animals.The rat was scored under light ether anesthesia. Perfusion of the heart was carried out through the aorta using Langendorf solution of the following composition: 150 mM NaCl, 5 mM KCl, 2 mM NaHCO3, 1 mM MgCl2, 2.5 mM CaCl2, 2 mM Tris-HCl (pH 7,4), 11 mM glucose. The solution was saturated with oxygen and heated to 37oC. To simulate ischemia and reperfusion on 20 min off the original solution and then perfesional heart normal solution Hears D. Y et al. Protection of the ischemic myocardium; cardioplegia.-N. Y, Raien Press. -1 is eskay contracture (for this purpose, registered diastolic pressure in the left ventricle), during reperfusion development reperfusion contracture, reconstruction of the amplitude of contractions (including that of the amplitude of at least 50% from baseline), the output of myoglobin, actinolite (adenosine+inosine+hypoxanthine), pyridine nucleotide (NADH+NADPH).In the control reperfusion arrhythmias was observed in 100% of cases, including ventricular fibrillation in 37.5% of the amplitude of the heartbeat was restored 12.5% (Fig. 1). The overall picture of the dynamics of the amplitude of the contractions shown in Fig. 2.Example 2. Series with timagenes 8 animals.Conditions experience was different in that for 5 minutes before doing ischemia heart was perfesional solution containing timogen at a concentration of 0.3 μm, which corresponds to the dose of the drug 7,15 ág/kgOn the model of ischemia and reperfusion, the drug significantly reduced the number of reperfusion arrhythmias (from 100% to 16.6%), completely prevented the development of ventricular fibrillation (Fig. 1); contributed to the restoration force of myocardial contractions (control of 12.5% in the experience of 100% (Fig. 1, 2), prevented the development of ischemic contracture (Fig. 3). During reperfusion, the drug prevented the increase in diastolic pressure in the left ventricle (Fig. 3), reduced the release into the flowing perf.Example 3. Series with verapamil 8 animals.Conditions of experience differed from the control by the fact that for 5 minutes before playing ischemia heart was perfesional solution containing verapamil at a concentration of 0.2 μm (Hears D. Y. et al. Protection of ischemic myocardium: cardioplegia. N. Y. 1981, P. 73-79).Reperfusion arrhythmias was observed in 87.5% of cases, in the remaining 12.5% of the heart is not restored contractile activity. Fibrillation verapamil prevented completely. From developed arrhythmias 12.5% over asistoliei, i.e., the total number of hearts with zero amplitude of contractions was 25% (Fig. 1). The amplitude of contractions was not restored to the initial level (Fig. 2).Verapamil reduced the degree of ischemic contracture, but had little impact on reperfusion (Fig. 3).The drug reduced the release of pyridine nucleotides (Fig. 5), but increased the output Danilovich (Fig. 4) and significantly increased the release of myoglobin (Fig. 6) compared with the control, i.e., he increased the depth of cytolysis.Thus, timogen limited the severity of the complications and consequences of induced ischemia and reperfusion of the heart, making it more effective than verapamil.Using this method, you can prevent arrhythmia b induced in the experiment ischemia of the heart.
< / BR>the way they are received and to farbkomposition based on them
FIELD: organic chemistry, medicine.
SUBSTANCE: invention relates to applying compounds of the formula (I) for preparing an antibacterial composition and veterinary composition eliciting with the enhanced activity.
EFFECT: valuable properties of agents.
4 cl, 3 tbl, 78 ex
FIELD: organic chemistry, biochemistry, medicine, pharmacy.
SUBSTANCE: invention relates to macrocyclic peptides of the general formula (I): wherein W means nitrogen atom (N); R21 means hydrogen atom (H), (C1-C6)-alkoxy-, hydroxy-group or N-(C1-C6-alkyl)2; R22 means hydrogen atom (H), (C1-C6)-alkyl, CF3, (C1-C6)-alkoxy-group, (C2-C7)-alkoxyalkyl, C6-aryl or Het wherein het means five- or six-membered saturated or unsaturated heterocycle comprising two heteroatoms taken among nitrogen, oxygen or sulfur atom and wherein indicated Het is substituted with radical R24 wherein R23 means hydrogen atom (H), -NH-C(O)-R26, OR26, -NHC(O)-NH-R26, -NHC(O)-OR26 wherein R26 means hydrogen atom, (C1-C6)-alkyl; R3 means hydroxy-group or group of the formula -NH-R31 wherein R31 means -C(O)-R32, -C(O)-NHR32 or -C(O)-OR32 wherein R32 means (C1-C6)-alkyl or (C3-C6)-cycloalkyl; D means a saturated or unsaturated alkylene chain comprising of 5-10 carbon atoms and comprising optionally one-three heteroatoms taken independently of one another among oxygen (O), sulfur (S) atom, or N-R41 wherein R41 means hydrogen atom (H), -C(O)-R42 wherein R42 means (C1-C6)-alkyl, C6-aryl; R4 means hydrogen atom (H) or one-three substitutes at any carbon atom in chain D wherein substitutes are taken independently of one another from group comprising (C1-C6)-alkyl, hydroxyl; A means carboxylic acid or its alkyl esters or their derivatives. Invention relates to pharmaceutical compositions containing indicated compounds and eliciting activity with respect to hepatitis C virus and these peptides inhibit activity of NS3-protease specifically but don't elicit significant inhibitory activity with respect to other serine proteases.
EFFECT: valuable biochemical and medicinal properties of peptides.
106 cl, 9 tbl, 61 ex
FIELD: organic chemistry, medicine, pharmacy.
SUBSTANCE: invention relates to compounds of the formula (I):
wherein r = 1, 2 or 3; s = 0; t = 0; R1 is taken among group including R11-CO and R12-SO2- wherein R11 is taken among group including (C6-C14)-aryl, (C1-C8)-alkyloxy-group wherein all given group are unsubstituted or substituted with a single or some similar or different substitutes R40; R12 means (C6-C14)-aryl wherein indicated group is unsubstituted or substituted with a single or some similar or different substituted R40; R2 means R21(R22)CH-, R23-Het-(CH2)k-, R23(R24)N-(CH2)m-D-(CH2)n- or R25(R26)N-CO-(CH2)p-D-(CH2)q- wherein D means bivalent residue -C(R31)(R32)-, bivalent (C6-C14)-arylene residue or bivalent residue obtained from aromatic group Het comprising 5 or 6 atoms in cycle among them 1 or 2 are similar or different cyclic heteroatoms taken among group including nitrogen and sulfur atoms; numbers k, m, n, p and q = 0, 1, 2; R21 and R22 that are independent of one another can be similar or different and taken among group including hydrogen atom, (C1-C12)-alkyl, (C6-C14)-aryl and so on; R23 means hydrogen atom, R27-SO2- or R28-CO-; R24, R25 and R26 mean hydrogen atom; R27 is taken among group including (C1-C8)-alkyl, (C6-C14)-aryl and so on; R28 is taken among group including R27, (C1-C8)-alkyloxy-group; R31 and R32 mean hydrogen atom; R40 is taken among group including halogen atom, hydroxy-, (C1-C8)-alkyloxy-group, (C1-C8)-alkyl, (C6-C14)-aryl and so on; R91, R92, R93 and R96 means hydrogen atom; R95 means amidino-group; R97 means R99-(C1-C8)-alkyl; R99 is taken among group including hydroxycarbonyl- and (C1-C8)-alkyloxycarbonyl-; Het means saturated, partially unsaturated or aromatic monocyclic structure comprising from 3 to 6 atoms in cycle among them 1 or 2 are similar or different heteroatoms taken among group comprising nitrogen and sulfur atoms; in all its stereoisomeric forms and also their mixtures in any ratios, and its physiologically acceptable salts. Invention proposes a method for preparing compound of the formula (I). Also, invention proposes a pharmaceutical preparation eliciting inhibitory activity with respect to factor VIIA and containing at least one compound of the formula (I) and/or its physiologically acceptable salts and pharmaceutically acceptable carrier. Invention provides preparing compounds of the formula (I) eliciting power anti-thrombosis effect and useful for treatment and prophylaxis of thrombosis-embolic diseases.
EFFECT: valuable medicinal properties of compounds and composition.
10 cl, 70 ex
FIELD: organic chemistry and drugs.
SUBSTANCE: New class of compounds of general formula 1, where R has formula 2 or 3; other residues are as described in claim of invention is disclosed. Said compounds are interleikyn-1β converting enzyme (ICE) inhibitors and have specific structural and physicochemical properties. Invention also relates to pharmaceutical composition containing said compounds. Compounds and composition of present invention are particularly useful in ICE activity inhibition and thereby can be used as drug for treating of diseases mediated by IL-1, apoptosis, IGIF and IFN-γ, as well as inflammations, autoimmune diseases, bone-destructive disorder, infections, disorder associated with cell proliferation, degenerative and necrotic disorders. Uses of claimed compounds and compositions as well as methods for production of N-acylamino compounds also are disclosed.
EFFECT: effective interleikyn-1beta converting enzyme inhibitors.
64 cl, 35 ex, 35 tbl, 21 dwg
FIELD: medicine, gastroenterology.
SUBSTANCE: traditional eradication therapy should be supplemented with licopid at the dosage of 10 mg per os once daily before breakfast for 10 d. The present innovation prevents transfer of microorganisms into inactive form, accelerates restoration of mucosal epithelial layer in gastroduodenal area, provides complete eradication of microorganisms, that in its turn, favors to prevent disease exacerbation and restoration of gastroduodenal functions.
EFFECT: higher efficiency of therapy.
3 dwg, 2 ex
FIELD: biotechnology, biochemistry.
SUBSTANCE: invention relates to producing the biologically active complex eliciting antioxidant and immunomodulating activity and used in medicine, cosmetics, veterinary science and food industry. The biologically active complex preparing by enzymatic hydrolysis of muscle tissue represents complex of biologically active compounds involving carnosine and anserine in the amount 85-97 wt.-% of the native content of these components in poultry muscle tissue, 1-7 weight parts of amino acids, 0.5-12 weight parts of oligopeptides of molecular mass 10 kDa, not above, and 0.1-15 weight parts of cyclic and polycyclic phenolic compounds as measured for 1 weight part of carnosine and anserine in the complex. This complex is prepared by enzymatic hydrolysis of milled and homogenized water muscle tissue in preferable dilution homogenate with water in the range 0.2-0.6 and with using proteolytic enzymes in the amount 2-5 wt.-% of the protein content and working at pH 4.5-8.5 and at enhanced temperature being preferably at 45-65°C. Product is isolated as extract or powder prepared in drying the extract. Invention provides enhancing effectiveness of the claimed complex.
EFFECT: improved method for preparing, valuable properties of complex.
7 cl, 6 tbl, 6 ex
FIELD: medicine, cardiology, gastroenterology.
SUBSTANCE: invention relates to a method for treatment of ulcer-erosion injures in gastroduodenal region in patients with arterial hypertension. Method involves detection of immune disturbances and carrying out the combined immunomodulating therapy and hypotensive therapy. Immunocorrecting complex consists of licopide, cortexinum, vetoronum TK in arterial hypertension of I-II degree and comprises superlymph additionally in arterial hypertension of III degree. Method provides attaining optimal results in treatment for relatively short time due to adequate immunocorrection in such patients.
EFFECT: improved method for treatment.
5 cl, 6 tbl, 2 ex
FIELD: organic chemistry, medicine, pharmacology.
SUBSTANCE: invention relates to new inhibitors of thrombin of the formula (I)
method for their preparing, intermediate compounds used for their preparing of the formula (II)
and a pharmaceutical composition comprising compounds of the formula (I). Invention provides enhancing effectiveness in inhibition of thrombin.
EFFECT: improved preparing method, valuable medicinal properties of compounds.
23 cl, 61 ex
FIELD: medicine, pharmacy.
SUBSTANCE: invention relates to a combined medicinal agent used in treatment of arterial hypertension. The proposed agent comprises the combination of enalapril maleate and hydrochlorothiazide as an active component, and also sodium hydrocarbonate, starch, lactose, iron oxide and stearate as accessory substances. The proposed agent is stable in storage and releases the active component easily.
EFFECT: improved and valuable properties of agent.
8 cl, 1 tbl, 5 ex
FIELD: veterinary science, pharmacy.
SUBSTANCE: invention proposes a composition for antioxidant protection of cells, tissues and a whole body against hyperproduction of free radicals in acute inflammation, chemical thermal and radiation damages. The composition comprises peroxyredoxin Prx VI and, additionally, lipoic acid and pharmaceutically acceptable additives. The composition comprises peroxyredoxin Prx VI and dihydrolipoic acid taken in the effective amount in the ratio peroxyredoxin Prx VI to dihydrolipoic acid in the range (w/w) from 1:1 to 50:1 wherein peroxyredoxin Prx VI can represents human recombinant peroxyredoxin Prx VI. Also, invention relates to a method for enhancing antioxidant protection of mammals involving delivery of indicated pharmaceutical composition is carried out into intercellular space of tissue, organ or a whole body of mammal. The delivery can be carried out by passive or active diffusion in application or spraying, by parenteral or endolumbal administration by injection, by parenteral administration, infusion, inhalation, drainage, by sublingual, vaginal or rectal administration, by nasal or ophthalmic drops. Except for, the delivery can be carried out with using other therapeutic agent, in particular, interferon simultaneously. Invention provides prophylaxis of secondary alternative damages, recovery of epithelial tissue, protection of biomacromolecules against effect of irradiation.
EFFECT: valuable medicinal properties of composition.
6 cl, 9 tbl, 11 dwg, 45 ex