Agent inhibition of platelet aggregation
(57) Abstract:2-Semicarbazone 1,2-naphthoquinone is used as an agent for inhibiting platelet aggregation. The drug after administration of 10 mg/kg/day to rats significantly inhibits platelet aggregation caused by ADP or thrombin. table 1. This invention relates to new uses of derivatives of beta-naphthoquinone, and their salts.Special patent medicine 954 M describes the use of medicines derived beta-naphthoquinone. In this patent, these derivatives are described as having hemostatic properties and vitamin properties.It is known that platelets interact with coagulation factors and components of the walls of blood vessels and play a major role, on the one hand, favorable to maintain the integrity of blood vessels in hemostasis and, on the other hand, adverse, causing thrombosis and the development of atherosclerose.Continuing the study of the above-mentioned derivatives of beta-naphthoquinone, quite unexpectedly, the applicant has found that these latter possess significant inhibitory activity against platelet aggregation.Thus, this application concerns a new note is NH-CO-CH3or hydroxyl, and their additive salts of pharmaceutically acceptable mineral or organic acids, for receiving the medicines, allowing to inhibit platelet aggregation.Additive salts with pharmaceutically acceptable mineral or organic acids can be, for example, salts formed with hydrochloric acid, hydrogen bromide, idestam hydrogen, nitric, sulfuric, phosphoric, propionic, formic, benzoic, maleic, fumaric, succinic, tartaric, citric, oxalic, glyoxalase, aspartic acids, alkanesulfonyl, such as ethane-sulfonic acids and arylsulfonate, such as benzosulfimide.Among the derivatives of beta-naphthoquinone General formula (1) include, in particular:
the compound of formula (1), where R is the group-NH-CO-NH2and its additive salts with pharmaceutically acceptable mineral or organic acids;
the compound of formula (1), where R is the group-NH-CO-CH3and its additive salts with pharmaceutically acceptable mineral or organic acids;
the compound of formula (1), where R is oxygraph and its additive salts with pharmaceutically acceptable mineral or org to obtain drugs, allowing to inhibit platelet aggregation, can be distinguished, in particular, 2-semicarbazone 1,2-naphthoquinone, better known under the international name of naftazone. In the experimental part of this product is marked with the international abbreviation DCI.High inhibiting platelet aggregation activity, illustrated below in the experimental part, derived beta-naphthoquinone of formula (1) described above, as well as their additive salts with pharmaceutically acceptable mineral or organic acids can be used, for example, in the treatment or prevention of arterial thrombolytic complications (cerebrovascular disorders, myocardial infarction) or diseases of the veins (phlebitis) and all cardiovascular diseases associated with atherosclerosis (particularly the brain), in the treatment and prevention of ischemic complications in the treatment of trombotsitnoy disorders.The usual dose, changing depending on the product, treat the patient and the disease may be, for example, a dose of from 1 mg to 100 mg per day, introduced through the mouth or injected. At least one of these compounds can be in pharmaceutical compositions as an active start.E is Oh, commonly used in medicine, as, for example, tablets, coated tablets, gelatin pills, capsules, granules, suppositories, drugs or injections; they are obtained in the usual way. One or more active principles can be put into the excipients usually used in pharmaceutical compositions, such as talc, gum Arabic, lactose, starch, magnesium stearate, cocoa butter, aqueous or non-aqueous media, animal or vegetable fats, various wetting, dispersing agents, emulsifiers, preservatives.Methods of obtaining derivatives of beta-naphthoquinone of formula (1) and their salts are described in the technical literature. In particular, we can cite the methods described in the special patent on a medicine 924 M or in the French patent 2103504.The following are non-limiting examples of the nature of pharmaceutical compositions that may be used in carrying out the invention.Example 1. Received the tablets of the following composition:
Naftazone 10 mg
Excipient in sufficient quantity for one of the finished tablets 150 mg
(Example excipient: lactose, starch, talc, magnesium stearate).Example 2. Was received injection of the following composition:
Naftazone is Casona in 200 ml of acetic anhydride. After heating for 10 h at 140oC, and then cooling, filtration, extraction of the precipitate with chloroform, evaporation to dryness, the absorption of ethanol, treatment with activated carbon, filtration and slow crystallization gain of 5.1 g of product corresponding to the formula (1), where R = -NH-CO-CH3(microcrystalline powder, ochre-yellow, so pl. = 137 - 138oC).Pharmacological studies.1 - Inhibition of platelet aggregation. Currently, many compounds can inhibit platelet function, but only two aspirin and ticlopidine have recognized activity: inhibition of platelet aggregation outside of a living organism (ex vivo).Therefore, naftazone emanated compared with ticlopidine and aspirin out of the living organism on the rat and, in another case, in vitro on platelet rats and humans.In the test tube. Platelet aggregation in humans and rats, tanned from their plasma induced by adenosine diphosphate (ADP) or thrombin, in the presence of different concentrations of naftazone (10-4M to 10-8M) significantly and statically decreased significantly. The reduction was 70 - 20% for concentrations of naftazone respectively from 10-4M to 10-6M.the following sequential injection of 10 mg/kg/day of naftazone, the inhibition of platelet aggregation caused by ADP or thrombin, was substantial and statistically significant (table).The results of the aggregation induced by thrombin or ADP, expressed in percent optical transmittance (average C. O.). The number of one and the same column bearing the same letters differ statistically significantly (at least p < 0,05) according to the method of aggregation Newman-Keuls.Thus, the results show that in these experimental conditions naftazone inhibits platelet aggregation caused by ADP or thrombin. This inhibition demonstrated in vitro in human platelets and platelets of rats, confirmed outside of a living organism in rats. In addition, this effect is equivalent to the action of ticlopidine and aspirin at the same conditions.S. O. = Standard otklonenie Application 2-semicarbazone 1,2-naphthoquinone as an agent that allows you to inhibit platelet aggregation.
FIELD: medicine, anesthesiology, resuscitation.
SUBSTANCE: one should perform puncturing of epidural space at Th12-L1 level. Through the lumen of puncture needle one should introduce catheter to move it cranially at the depth of 3 cm. After that one should inject 10 ml 05%-marcaine solution to perform repeated injections per 5.0 ml every 4 h during 1-8 d. The effect is achieved due to unloading minor cycle of circulation.
EFFECT: higher efficiency of therapy.
FIELD: medicine, pharmacy.
SUBSTANCE: invention proposes new tablets with size less 3 mm with sustained-releasing the opioid analgesic drug for 30 min in the amount above 75%. Invention provides opioid for oral intake with taking into account individual necessity of patient due to selection of required amount of mictotablets by dispenser.
EFFECT: valuable properties of tablet, expanded assortment of medicinal formulations of opioid analgesics.
19 cl, 4 tbl, 4 ex
FIELD: medicine, endocrinology.
SUBSTANCE: the present innovation deals with preventing diabetes mellitus and its aftereffects. It is suggested to apply sibutramin and its analogs to decrease non-susceptibility to insulin in diabetes-free patients, prevent decreased tolerance to glucose and decrease the quantity of introduced insulin in diabetes-suffering patients and normalize body weight, as well.
EFFECT: higher efficiency of application.
28 cl, 3 dwg, 1 tbl
FIELD: organic chemistry, medicine, pharmacy.
SUBSTANCE: invention relates to new derivatives of benzene of the formula (I): wherein A represents a group taking among the following groups: -C≡C-, -CH=CH-, -CH2-CH2; n = 1 or 2; X represents hydrogen, chlorine or fluorine atom or methyl or methoxy-group; Y represents hydrogen, chlorine or fluorine atom; R1 represents cyclohexyl group monosubstituted, disubstituted, trisubstituted or tetrasubstituted with methyl group, phenyl group monosubstituted or disubstituted with fluorine or chlorine atom or methoxy-group, cycloheptyl, tert.-butyl, dicyclopropylmethyl, 4-tetrahydropyranyl or 1- or 2-adamantyl, or adamantine-2-ol group; or R1 represents phenyl group and in this case X and Y both represents chlorine atom; R2 represents hydrogen atom or (C1-C4)-alkyl group; R3 represents (C5-C7)-cycloalkyl, and salts of these compounds formed by addition of pharmaceutically acceptable acids, and their solvates and hydrates also. Also, invention relates to methods for preparing compounds of the formula (I) and to pharmaceutical composition able to interact with receptors sigma-2 based on these compounds. Invention provides preparing new compounds and medicinal agents based on thereof for treatment of autoimmune states, disturbance on heart contraction frequency and control against proliferation of tumor cells.
EFFECT: improved preparing methods, valuable medicinal properties of compositions.
18 cl, 14 tbl, 78 ex
SUBSTANCE: method involves administering typical tricyclic antidepressants combined with selective reverse serotonin capture inhibitors. Anxious version of subpsychotic level depressive syndrome of endogenous genesis being treated, intravenous drop-by-drop infusion of 2.-4.0 ml of 1% amitriptiline solution per 200 ml of physiologic saline is applied in 12-14 procedures combined with selective reverse serotonin capture inhibitor given per os, Zoloft is per os administered as the inhibitor at a dose of 50-100 mg. Then, supporting Zoloft therapy is applied at a dose of 100 mg during 3 months. Atypic version of depressive syndrome of subpsychotic level and endogenous genesis is treated with intravenous drop-by-drop infusion of 1.25% Melipramine solution at a dose of 2.0-4.0 ml per 200 ml of power supply source in 12-14 infusions combined with a reverse serotonin capture inhibitor. Paxyl is taken at a peroral dose of 40-60 mg as the inhibitor. Then, supporting Paxyl therapy is applied at a dose of 40-60 mg during 3 months.
EFFECT: enhanced effectiveness of treatment; reduced risk of complications; accelerated depressive syndrome relief.
SUBSTANCE: the suggested transdermal therapeutic system (TTS) is indicated for percutaneous injection of tolterodin for several days. It is, also, described the method for its manufacturing. The suggested TTS is being a self-gluing lamellar matrix structure that contains methacrylate copolymer including ammonium groups, at least, one plastifier and up to 25 weight% tolterodin. TTS is of good tolerance by skin and is of good physical and chemical stability at prolonged storage and application, it, also, has got good adhesive properties and can provide the penetration of maximal quantity of active substance through skin.
EFFECT: higher efficiency of application.
8 cl, 2 dwg, 3 ex, 3 tbl
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
SUBSTANCE: method involves applying fractal introduction of 0.2 mg/kg MT calypsol and 0.4 mcg/kg MT fentanyl every 10 min during operation. Additional local spinal cord root irrigation with 2% lidocaine solution at maximum traumatic operation moment.
EFFECT: enhanced effectiveness of treatment; preserved spontaneous patient respiration.
FIELD: organic chemistry, medicine.
SUBSTANCE: invention reports about preparing new substituted derivatives of 2-dialkylaminoalkylbiphenyl of the general formula (I):
wherein n = 1 or 2; R1 means cyano-group (CN), nitro-group (NO2), SO2CH3, SO2CF3, NR6aR7a, acetyl or acetamidyl; R2 means hydrogen atom (H), fluorine atom (F), chlorine atom (Cl), bromine atom (Br), cyano-group (CN), nitro-group (NO2), CHO, SO2CH3, SO2CF3, OR6, NR6R7, (C1-C6)-alkyl, acetyl or acetamidyl being alkyl can comprise one or more similar or different substitutes taken among halogen atom or hydroxy-group; or R1 and R mean in common group -OCH2O, -OCH2CH2O, CH=CHO, CH=C(CH3)O or CH=CHNH; R3 means H, F, Cl, Br, CN, NO2, CHO, SO2CH3, SO2CF3, OR6, NR6R7, (C1-C6)-alkyl, acetyl or acetamidyl being alkyl can comprise one or more similar or different substitutes taken among halogen atom or hydroxy-group; R4 and R5 have similar or different values and mean hydrogen atom (H) or unsubstituted (C1-C6)-alkyl; R6 and R7 have similar or different values and mean hydrogen atom (H) or unsubstituted (C1-C6)-alkyl; R6a means hydrogen atom (H) or unsubstituted (C1-C6)-alkyl; R7a means unsubstituted (C1-C6)-alkyl as their bases and/or salts of physiologically acceptable acids, with exception of compound representing 4-chloro-2'-dimethylaminomethylbiphenyl-2-carbonitrile and to a method for their preparing. Derivatives of 2-dialkylaminoalkylbiphenyl can be used in medicine for treatment or prophylaxis of pains, inflammatory and allergic responses, depressions, narcomania, alcoholism, gastritis, diarrhea, enuresis, cardiovascular diseases, respiratory ways diseases, cough, psychiatry disorders and/or epilepsy.
EFFECT: valuable medicinal properties of compounds.
13 cl, 2 tbl, 43 ex
FIELD: obstetrics and gynecology.
SUBSTANCE: over a 2-5 day period, 2.0 ml of Ginipral is administered once a day intravenously in a drop-by-drop manner followed by intravenously drop-by-drop administered 30-40 min later 2.0 ml of Instenone and, in the evening, 1 dragee Instenone orally. Afterwards, Instenone and Ginipral are administered orally: the former in dose of 1 dragee thrice a day with meal and the latter in dose of 1 pellet four times a day after meal until symptoms of the risk of prevention of pregnancy disappear.
EFFECT: prolonged pregnancy and prevented premature birth, which favors reduced irritation, normalized tonus, contractive activity of uterus, and improved psychic and emotional state of women.