Drug for the treatment of atherosclerosis and its complications
(57) Abstract:The invention relates to medicine, namely to the production of medicines on the basis of [N-methyl-N-(D-glyukopiranozil)ammonium-2(acridin-9-one-10-yl)acetate]cycloferon, and can be used for the treatment of atherosclerosis and its complications. The objective of the invention is the provision of quality and effective low-toxicity universal tool for the treatment of atherosclerosis and its complications. The problem is solved in that the medicinal product containing the active substance and the solvent, as the active substances included the compound N-methyl-N-(a, D-glyukopiranozil)ammonium-2-(acridin-9-one-10-yl)acetate, and the solvent is water in the following ratio, wt.%: active substance 18,0-22,5; water - the rest. 3 table. The invention relates to medicine, namely to the production of medicines on the basis of [N-methyl-N-(D-glyukopiranozil)ammonium-2(acridin-9-one-10-yl)acetate] cycloferon (application trademark N 93006831/50 from 24.03.93), and can be used for the treatment of atherosclerosis and its complications.Known parenteral form of the medicinal product based on the chemical analogue of cycloferon salmenniemi composition:
as active substances substituted acridine sodium salt of 10-carboxymethyl-8-acridine structural formula
< / BR>surfactant;
water is the solvent.The tool was not used for the treatment of atherosclerosis.Known means at the specified prototype has the following disadvantages:
expressed irritating and painful action, due to the high pH value (9,0);
the risk of necrosis and gemokoagulyatsii;
insufficient concentration of the active substance (50 mg/ml 5%), which requires an increase in the volume of injectate for the manifestation of therapeutic effect (up to 10 ml or more).In order to reduce pain effect with the drug we were trying stabilization specified in the prototype dosage forms allowed in the Pharmacopoeia by means of, for example, buffer solutions and complexing agents. During the experiment, we tried to reduce the pH of the dosage form below to 8.0, but this did not lead to any positive result. At pH below 8.0 a gradual precipitation of acridan-acetic acid, which testifies to the impossibility of creating a qualitatively is documentatie means, eliminating or reducing risk factors, and medications, such as various hypolipidemic (cholestyramine, polysporin, linecol, heparin, chondroitin sulfate, etc.) (Mashkovsky M. D. Medicines, including 1 and 2. M. Medicine, 1987, T. 2, S. 89, 92, 73, 156).None of the existing lipid is not universal, and almost all have side effects. The search for new anti-sclerotic funds are among the various classes of chemical compounds:
derivatives of urea and thiourea (U.S. patent N 4397868, 4387105, 4623662);
derivatives of aminobenzoic acid (EPO application 0170361, CBL. application Japan 59-24135, 63-26729);
benzothiazine (EPO, 0174458);
derivatives of indole (UK application N 2190587);
derivatives hexahydronaphthalen (U.S. patent N 4444784).The most common medication used for the treatment of atherosclerosis, is clofibrate (mickleton, lipomed, atromid) isobutyrate (Mashkovsky M. D. Medicines, including 1 and 2. M. Medicine 1987, H. 2, S. 90) prototype treatment. It reduces blood levels of lipoproteins that are rich in cholesterol and triglycerides. It is used for atherosclerosis with increased blood levels of these substances., syvaet some side effects. It can cause intrahepatic cholestasis, accompanied by the formation of stones in the gall bladder and biliary tract.The task of the invention is the provision of quality and effective low-toxicity universal tool for the treatment of atherosclerosis and its complications.The problem is solved in that the medicinal product containing the active substance and the solvent, as the active substances included the compound N-methyl-N - (D-glyukopiranozil)ammonium-2-(acridin-9-one-10-yl)acetate formula
and as a solvent water in the following ratio, wt. active substance 18,0-22,5; water the rest.Currently, medical-biological tests have proved that the effective daily therapeutic dose of cycloferon is 360-450 mg per person in a single dose. In accordance with the proposed therapeutic dose of the applicant has been a lot of work to create effective and high-quality pharmaceutical form. The development of the dosage form was carried out for vials with a volume of 1.2 and 5 ml applied to obtain a standard dosage forms.To receive parenteral Lek who ranks number allowed in the Pharmacopoeia of the N-methylglucamine.Dosage form obtained according to the method described below.The results of the studies are given in table. 1.From table. 1 shows that when using N-methylglucamine less of 96.5 g dosage form is not stable: formed turbidity or precipitation during storage. When using N-methylglucamine more of 96.5 g of the solution has a pH above 9.0 and has a strong local irritant effect. Thus, the optimal ratio of components is of 96.5 g of N-methylglucamine 125 g greenexpo acid in aqueous solution.Taking into account the optimal ratio of components of the dosage form, the optimal therapeutic daily dose of 360-450 mg per person, single administration, as well as manufactured standard vials (1, 2 and 5 ml) was obtained the optimal concentration of active substance in the dosage form - 18,0-22.5 wt.The results of the studies are given in table. 2.As follows from the table. 2, when use vials with a volume of 5 ml with a concentration of active substance of 7.2-9.0% of the volume of solution is too large for a single injection. When using vials in 1 ml with a concentration of active substance 45,0% dosage form is not techno table. 3 shows the comparative characteristics of qualitative indicators of the claimed dosage forms and prototype structural entity.As follows from the table. 3, the claimed medicinal product has the following advantages:
the complete absence of irritating and painful steps in injecting drug due to close to physiological pH (blood pH 7,3);
in 5-20 times higher concentration of the active substance in solution, allowing to obtain a pronounced therapeutic effect with minimal amounts of administered drug;
the absence of biogenic particles (chelating agents, components, buffer);
upon receipt of the dosage form does not require special equipment for sealing ampoules under inert gas.A formulation was prepared as follows. In chemical beaker with a capacity of 2 litres pour 1 liter of water for injection, load 193 g N methylglucamine, stir until dissolved and add 250 g greenexpo acid and again stirred until dissolution. Control of pH potentiometric, bring the solution volume to 2 l with water for injection, filtered through Millipore and poured into ampoules and vials. The ampoule is carlavirus.As a result of biomedical research has been proved to be highly effective drugs in the treatment of atherosclerosis and its complications.Example 1. Patient B. 54 years, locksmith, was admitted to the Department 2.08.91, with complaints about squeezing pain in the heart and behind the sternum, in the left hand, periodic bouts of increased frequency of breathing with episodes of transient loss of consciousness. Delivered by ambulance after 6 hours from the onset of the disease. A serious condition. The pulse rate of 108 beats in 1 min, arrhythmic. AD - 130/100, BH 18 minutes ECG acute phase of focal lesions in the posterior wall of the left ventricle. Ventricular extrasystoles. AV block II degree (2: 1). D-C: IHD. Acute transmural myocardial infarction posterior wall of the left ventricle from 01.08.91, Ventricular extrasystoles. Introduced fibrinolitiki, lidocaine.At 9 o'clock 2.08 started a course of treatment of the claimed medicinal preparation. Just made 3 injections of the drug (2, 4, 6.08.91,) intramuscularly with 2 ml of 22.5% solution.The condition and the patient's health improved immediately after injection and remained satisfactory during the whole observation time, rhythm and conductivity normalizada is 156 g/l and erythrocyte from 4.5 to 5,21012l, and white blood cells (lymphocytes increased in 4 times), the repeated clinical, biochemical and instrumental investigations (ECG, EchoCG) showed a clear positive trend (in particular, 10.08 have no data for the transmural nature of the lesion of the myocardium). Discharged 1.09 in satisfactory condition.Thus, this example demonstrates the positive effect of the drug in complicated transmural myocardial infarction caused by severe atherosclerosis of the coronary arteries in a patient with middle age.Example 2. Patient F. 70 years, was admitted to the Department 7.08.91 with complaints of pain in the heart area and pressing nature, interruption of cardiac activity, shortness of breath, weakness. Delivered by ambulance. A serious condition. Pale skin, cyanosis of the lips. The apical thrust is spilled, heart expanded to the left, rough systolic murmur at all points. I tone weakened, the accent of II tone on the pulmonary artery. Congestive rales in the lungs. Liver +2,5 see ECG deterioration of coronary circulation in the area of the scar, the rise of T2-U5.D-C: IHD. Re myocardial infarction from 07.08. The paroxysm of atrial fibrillation.Amid the usual treatment of conduct).In the treatment of arrhythmia stopped and never resumed, the health and condition has improved significantly. Positive changes from red and white blood cells, similar to that shown in example 1, ECG normalization of the ST segment on the 2nd day after receipt, the positive dynamics of clinical, ECG, echocardiography and biochemical parameters. Discharged 6.09 in satisfactory condition. This example demonstrates the positive effect of the drug on the course of recurrent myocardial infarction in a patient of advanced age caused by atherosclerosis of the coronary vessels.Example 3. Patient S. 70 years, was admitted to the Department 12.08.91 with complaints dramatically increased shortness of breath, arrhythmia. A serious condition. Swelling in the legs, ascites, and right-sided hydrothorax. ECG from 12.08. atrial fibrillation. The modified form of the ventricular complex in left chest leads. Amid the usual treatment is a course of injections of the drug 13, 15 and 17.08.91, similar to those described in examples 1 and 2.D-C: IHD. Acute re-myocardial infarction from 12.08. Postinfarction cardiosclerosis. Atrial fibrillation tachysystolic form NC II B III Art.On treatment immediately stopped shortness of breath, became gradually the part to go. Positive developments in instrumental (ECG, echocardiography, clinical and biochemical studies (in particular, from the red and white blood cells) is similar to the above.This example demonstrates the positive effect of the drug in the patient with severe heart failure on the background of recurrent myocardial infarction caused by atherosclerosis.This drug belongs to a new class of drugs that have immunomodulatory effects and showed a definite positive effect in the treatment of atherosclerosis and its complications such as myocardial infarction. Drug for the treatment of atherosclerosis and its complications, containing the active substance and a solvent, characterized in that the active substance it contains the compound N-methyl-N (D-glyukopiranozil)ammonium-2-(acridin-9-one-10-yl)acetate formula
< / BR>and as a solvent water in the following ratio, wt.Active substance 18,0 -22,5
FIELD: organic chemistry, natural compounds, medicine, oncology.
SUBSTANCE: invention represents new saponin mixtures used for inhibition of initiation and activation of mammalian epithelial cell in pre-malignant or malignant state, for stimulation of apoptosis of mammalian malignant cell, prophylaxis of anomalous proliferation of mammalian epithelial cell, for treatment of inflammatory and regulation of angiogenesis in mammal. These mixtures are isolated form plants of species Acacia victoriae. Also, invention relates to methods for their applying. These compounds can comprise triterpene component, such as acacic or oleanolic acid to which oligosaccharides and monoterpenoid components are joined. Mixtures and compounds elicit properties associated with regulation of apoptosis and cytotoxicity of cells and strong anti-tumor effect with respect to different tumor cells.
EFFECT: valuable medicinal properties of compositions.
43 cl, 53 tbl, 50 dwg, 44 ex
FIELD: organic chemistry, chemical technology, medicine, oncology, pharmacy.
SUBSTANCE: invention relates to new derivative of taxane of the formula (I):
that elicits strong antitumor effect. Also, invention relates to intermediates substances, a method for preparing compound of the formula (I), a method for preparing 1,14-β-hydroxy-1,14-carbonate-baccatin III-derivatives substituted with isoserine residue at position 3 and to pharmaceutical composition based on compounds of the formula (I). Invention provides preparing new derivative of taxane that elicits higher activity and reduced toxicity as compared with paclitaxel.
EFFECT: improved preparing method, enhanced and valuable medicinal properties of compound.
10 cl, 7 tbl, 6 ex
FIELD: organic chemistry, medicine, pharmacy.
SUBSTANCE: invention relates to new derivatives of borrelidin of the general formula (I)
wherein R represents the group of the general formulae -COOR1, -CONR2R3, -CONR4CONR2R5 or -CH2OR6 wherein R1 represents (C2-C6)-alkyl group, (C1-C6)-alkyl group substituted with hydroxyl group or 5-8-membered saturated nitrogen-containing heterocyclic group (it can comprise oxygen atom in addition to nitrogen atom) or 5-6-membered nitrogen-containing aromatic heterocyclic group or (C3-C6)-cycloalkyl group; R2 and R3 are similar or different and represent independently hydrogen atom or (C1-C6)-alkyl group that can be substituted optionally with hydroxyl, (C2-C5)-alkoxycarbonyl or 5-8-membered saturated nitrogen-containing heterocyclic group (it can comprises oxygen atom in addition to nitrogen atom) or 5-6-membered aromatic homocyclic group or aromatic heterocyclic group comprising oxygen and/or nitrogen atom, 5-6-membered cycloalkyl or heteroaryl group; R4 and R5 are similar or different and represent independently hydrogen atom or (C3-C6)-cycloalkyl group; R6 represents hydrogen atom; also, invention relates to tautomers, solvates of these compounds, their mixtures and acid-additive salts. Also, invention relates to pharmaceutical compositions comprising compounds of the general formula (I) as an active component. Angiogenesis inhibitors of the present invention inhibit formation of new vessels in tissues of live organisms and can be used for prophylaxis and inhibition of the angiogenesis process arising in the tumor proliferation, and for prophylaxis of formation of tumor metastasis. Invention provides preparing new derivatives of borrelidin eliciting the value physiological effect.
EFFECT: valuable medicinal properties of compounds.
8 cl, 15 ex
FIELD: medicine, hepatology.
SUBSTANCE: at achieving alkaline phosphatase of 580 U and more one should introduce ursodesoxycholic acid at the dosage of 15-20 mg/kg and orlistate at the dosage of 90-100 mg twice or thrice daily for patients with steatohepatitis. According to normalization of clinical and biochemical values of blood analyses it is possible to conclude upon successfulness of therapy performed. The method provides clinic-laboratory remission of the disease.
EFFECT: higher efficiency of therapy.
FIELD: medicine, pharmacy.
SUBSTANCE: invention relates to new acid-additive nitrate salts of compounds taken among salbutamol, cetirizine, loratidine, terfenadine, emedastine, ketotifen, nedocromil, ambroxol, dextrometorphan, dextrorphan, isoniazide, erythromycin and pyrazinamide. Indicated salts can be used for treatment of pathology of respiratory system and elicit an anti-allergic, anti-asthmatic effect and can be used in ophthalmology also. Indicated salts have less adverse effect on cardiovascular and/or gastroenteric systems as compared with their non-salt analogues. Also, invention proposes pharmaceutical compositions for preparing medicinal agents for treatment of pathology of respiratory system and comprising above indicated salts or nitrate salts of metronidazol or aciclovir.
EFFECT: improved and valuable properties of compounds.
6 cl, 5 tbl, 19 ex
FIELD: organic chemistry, medicine, oncology, pharmacy.
SUBSTANCE: invention relates to a new pentacyclic compound derivative of taxane represented by the formula:
wherein R1 represents dimethylaminomethyl group or morpholinomethyl group; R2 represents halogen atom or alkoxy-group comprising from 1 to 6 carbon atoms, or its salt eliciting an antitumor effect, and to a medicine agent based on its. Invention provides preparing new derivatives of taxane eliciting the valuable biological effect.
EFFECT: valuable medicinal properties of compound.
13 cl, 1 dwg, 4 tbl, 16 ex
FIELD: woodworking industry.
SUBSTANCE: invention relates to methods for recovering and purifying native bioflavonoids: dihydroquercitine and dihydrokaempferol from larch wood extracts. Method of recovering bioflavonoids from larch wood extracts is characterized by that freeze-dried extract is dissolved in ethylacetone/water mixture composed in specified proportion, specified amount of resulting solution is introduced into column filled with urea (sorbent) preliminarily equilibrated with ethylacetate, and column is then eluted with an ester and/or ketone having boiling point below 120°C, or with ethylacetate/acetone mixture at specified ratio. Eluate is collected and evaporated until crystallization is observed and then cooled. Separated crystals are rinsed and dried.
EFFECT: enabled single-step process for separating dihydroquercitine and dihydrokaempferol from resinous impurities and other polymeric compounds, reduced process expenses, and reduced environmental impact.
4 cl, 1 dwg
FIELD: organic chemistry, medicine, pharmacy.
SUBSTANCE: invention relates to new semi-synthetic taxanes of the formula (1):
wherein R and R1 can be similar or different and represent hydrogen atom (H), (C1-C18)-acyl group, benzoyl group; R2 and R3 represent hydrogen atom (H) or R2 and R3 in common form carbonate or thiocarbonate residue; R4 represents benzoyl group optionally substituted at meta-position; R' represents hydrogen atom (H) or (C1-C4)-alkyl; R'' represents (C1-C4)-alkyl or phenyl; R''' represents tert.-butoxy-group under condition that R and R1 both can't represent hydrogen atom (H). Also, invention relates to a pharmaceutical composition based on compounds of the formula (1) eliciting an anti-tumor, anti-angiogenic and anti-arthrosis effect. Invention provides preparing new compounds eliciting cytotoxicity comparable with cytotoxicity of other taxanes but showing reduced systemic toxicity that can be administrated by intravenous and oral routes.
EFFECT: valuable medicinal properties of compounds and pharmaceutical compositions.
6 cl, 1 tbl, 7 ex
FIELD: medicine, therapy, gastroenterology.
SUBSTANCE: method involves preliminary assay of the disorder type in gallbladder motor contraction and bile-excretion ways followed by prescribing thermal low-mineralized hydrocarbonate-sodium-sulfate-calcium-magnesium mineral water in the dose by 200-300 ml, 3 times per a day, 1 h before eating, tubages № 3 with mineral water, bathes and shower with mineral water every day for 10-14 days. In the hypotonic type of motor activity method involves mineral water at temperature 25-30°C, and in the hypertonic type - at temperature 38-40°C. Method provides accelerating in scars formation of ulcers and epithelization of erosions in gastroduodenal system, to prevent frequent exacerbations and to reduce activity of Chelicobacter-induced inflammation.
EFFECT: improved therapy method.
4 tbl, 2 ex
FIELD: organic chemistry, medicine, oncology, pharmacy.
SUBSTANCE: invention relates to new taxanes of the general formula (I)
wherein R2 means benzoyloxy-group; R7 means hydroxyl (OH); R9 means keto-group; R10 means R10aCOO-; R10 means (C2-C6)-alkyl, (C2-C6)-alkenyl, (C3-C6)-cycloalkyl or 5-6-membered heteroaromatic group wherein heteroatom represents oxygen atom (O), sulfur atom (S) or nitrogen atom (N); R14 means hydrogen atom (H); X3 means (C2-C6)-alkyl, (C2-C6)-alkenyl, (C3-C6)-cycloalkyl, phenyl substituted possibly with nitro-group (-NO2), 5-6-membered heteroaromatic group wherein heteroatom represents O, S or N; X5 means -COX10, -COOX10; X10 means (C2-C6)-alkyl, (C2-C6)-alkenyl, (C3-C6)-cycloalkyl, phenyl or 5-6-membered heteroaromatic group wherein heteroatom represents O, S, N; Ac means acetyl. Compounds of the formula (I) elicit antitumor activity.
EFFECT: valuable medicinal properties of compounds.
68 cl, 1 tbl, 6 ex