Compositions and methods for respiratory depression and related side effects of mu-opioid compounds
(57) Abstract:The invention relates to medicine, namely the method of reducing, treating or preventing mediated drug respiratory depression, muscle rigidity or nausea/vomiting in an animal related to the introduction of specified animal mixed Delta/mu opioid agonist or drugs, mediating respiratory depression, in which the animal receiving the specified medication, administered an effective amount of the compound-agonist Delta-receptor formula I. the Method allows you to more effectively reduce the specified respiratory depression, muscle rigidity or nausea/vomiting. 2 C. and 17 C.p. f-crystals, 2 ill., 1 PL.Description text in facsimile form (see drawings). Those 1. Method of reducing, treating or preventing mediated drug respiratory depression, muscle rigidity or nausea/vomiting in an animal related to the introduction of specified animal drugs, mediating respiratory depression, in which the animal receiving the specified medication, mediating respiratory depression, introducing an effective amount of the compound - agonist Delta-receptor formula
< / BR>6. The method according to p. 1, in which analgesia is mediated drug mediating respiratory depression, with a therapeutic index is the ratio of the ED50for respiratory depression to the ED50for analgesia, significantly exceeding therapeutic index of fentanyl, in which the animal is administered an amount of (+)-3-((R)--((2S, 5R)-4-allyl-2,5-dimethyl-1-piperazinil)-3-hydroxybenzyl)-N-(3-forfinal)-N-methylbenzamide, which is effective is own by p. 6, in which the specified therapeutic index substantially greater than 4.5.8. Pharmaceutical composition comprising: (1) an effective amount of bioactive compounds mediating respiratory depression, muscle rigidity and/or nausea/vomiting as its adverse effect; and (2) connection - agonist Delta-receptor formula
< / BR>where R1represents a C1-C6alkyl;
R represents a C1-C6alkyl or 6-membered aromatic ring, optionally having halogen Deputy,
or its pharmaceutically acceptable ester or salt.9. The pharmaceutical composition according to p. 8 also containing pharmaceutically acceptable carrier.10. The pharmaceutical composition under item 8, in which the connection agonist Delta-receptor represents a (-)-4-((R)--((2R, 5R)-4-allyl-2,5-dimethyl-1-piperazinil)-3-hydroxybenzyl)-N, N-diethylbenzamide or its pharmaceutically acceptable salt.11. The pharmaceutical composition under item 8, in which the bioactive compound contains opiate connection.12. The pharmaceutical composition under item 8, in which the bioactive compound contains opiate analgesic compounds connection.14. The pharmaceutical composition according to p. 13, in which the mu-opioid compound and agonist Delta-receptor are administered together.15. The pharmaceutical composition according to p. 14, in which the specified Delta agonist-receptor contains (+)-3-(R)--((2S, 5R)-4-allyl-2,5-dimethyl-1-piperazinil)-3-hydroxybenzyl)-N-(3-forfinal)-N-methylbenzamide.16. The pharmaceutical composition according to p. 14, in which the specified agonist at mu receptor selected from the anesthetic compounds and analgesic compounds.17. The pharmaceutical composition according to p. 14, in which the specified agonist at mu receptor selected from the group consisting of Alfentanil, fentanyl, morphine and its analogs.18. The pharmaceutical composition under item 8, in which the connection agonist Delta-receptor is a
< / BR>19. The pharmaceutical composition under item 8, in which the connection agonist Delta-receptor is a (+)-3-((R)--((2S, 5R)-4-allyl-2,5-dimethyl-1-piperazinil)-3-hydroxybenzyl)-N-(3-forfinal)-N-methylbenzamide.
< / BR>where G1- CH2; G2- C(O); m = 2 or 3, n is 0 or 1; R1is 1-3 substituent, independently selected from H, G, C1-C6alkoxy; R2is 1-3 substituent, independently selected from H, C1-C6alkoxy; R3means N or
< / BR>< / BR>< / BR>R4- H; Ar1means
< / BR>< / BR>R8means 1-3 substituent, independently selected from H, G; R9means N;
< / BR>< / BR>< / BR>where p = 1, 2, 3, or 4; X is-O-, -CH2-; R10-H, C1-C6alkyl or
< / BR>">< / BR>< / BR>< / BR>where q = 2 or 3; R5- C1-C4alkyl, (CH2)2HE; R6- C1-C4alkyl, -(CH2)2HE, (CH2)2N(CH3)2; R5', R6' - C1-C4alkyl; R7- C1-C6alkyl, and the stereoisomers and pharmaceutically acceptable salts
FIELD: organic chemistry, biochemistry, medicine, pharmacy.
SUBSTANCE: invention relates to new sulfur-containing compounds of the formula (I):
their pharmaceutically acceptable salts or solvates, or salt solvates wherein R1 represents (C1-C6)-alkyl, cycloalkyl, aryl, aliphatic or aromatic heterocyclyl substituted with one more basic group, such as amino-, amidino- and/or guanidine-group; R2 represents hydrogen atom (H), alkyl, alkylthio-, alkoxy- or cycloalkyl group; R3 represents COOR5, SO(OR5), SOR5 and others; R4 represents hydrogen atom (H) or (C1-C6)-alkyl; R6 represents hydrogen atom (H); X represents C(Z)2 or NR6CO; Y represents C(Z)2; Z represents hydrogen atom (H), (C1-C6)-alkyl, aryl or cycloalkyl. Indicated compounds inhibit activity of carboxypeptidase U and can be used for prophylaxis and treatment of diseases associated with carboxypeptidase U.
EFFECT: improved preparing method, valuable biochemical and medicinal properties of compounds.
14 cl, 36 ex
FIELD: medicine, oncohematology.
SUBSTANCE: the present innovation deals with treating elderly patients with chronic lympholeukosis accompanied with cardiovascular failure. The method deals with applying chemopreparations and cytoprotector. Moreover, 1 wk before the onset of chemotherapeutic therapy one should prescribe preductal at the dosage of 105 mg daily. At this background one should sample blood out of elbow vein at the volume of 200 ml into a vial with glugicir to centrifuge it, isolate plasma, divide into two portions, add into the 1st vial - cyclophosphan 600-800 mg/sq. m, vincristin 1.4 mg/sq. m, into the 2nd vial - adriamycin 50 mg/sq. m to be incubated for 30 min at 37 C and intravenously injected by drops for patients. Simultaneously, the intake of prednisolone should be prescribed at the dosage of 60 mg/sq. m since the 1st d and during the next 5 d and preductal at the dosage of 105 mg daily during a week, and then 2 wk more at the dosage of 60 mg daily. All the procedures should be repeated in above-mentioned sequence 4-6 times. The method enables to decrease toxic manifestations of chemotherapy while applying adequate dosages of cytostatics, anthracycline antibiotics, among them, at no great manifestations of their toxicity due to preductal's cardioprotective action.
EFFECT: higher efficiency of therapy.
1 ex, 5 tbl
FIELD: medicine, cardiology.
SUBSTANCE: it is suggested to apply cortisol antagonists in addition to clonidine while manufacturing preparation to treat heart failure. Moreover, one should introduce cortisol antagonist or a product that includes cortisol antagonist along with the second medicinal preparation being a combined preparation to be applied either simultaneously, separately or successively. The present innovation provides decreased symptoms of heart failure at decreasing cardiac muscle's fibrosis and heart sizes due to preferable impact upon glucocorticoid receptors in patient's heart and/or kidneys.
EFFECT: higher efficiency of application.
12 cl, 2 ex
SUBSTANCE: the present innovation deals with medicinal preparations designed as solution and indicated for therapeutic needs. Eye drops contain ciprofloxacin hydrochloride monohydrate being equivalent to 0.3% free foundation, a buffer system that keeps pH within 3.5-5.5 interval, as a conserving agent - benzalconium chloride and a s a stabilizer - the salt of disodium ethylenediamine tetraacetic acid, moreover, their range of osmolality values correspond to 150-450 mM/kg H2O. Eye drops should be obtained by preparing buffer system in which mannitol should be dissolved followed by the salt of disodium ethylenediamine tetraacetic acid, benzalconium chloride, ciprofloxacin hydrochloride. Then one should perform the control for the quality of obtained solution to be then filtered by applying sterilizing elements and packed. This innovation provides treatment of eyes at creating the pressure in an eye and at certain desired osmolality.
EFFECT: higher efficiency of therapy.
4 cl, 1 ex
SUBSTANCE: invention relates to endoparasitic agent containing cyclic depsipeptide of general formula 1 and piperazine of formula 2 .
EFFECT: endoparasitic agent with synergetic agent.
6 cl, 7 ex, 7 tbl
FIELD: medicine, oncology.
SUBSTANCE: the present innovation deals with treating oncological diseases. It is suggested to apply bisdioxopiperazine (previously known as cardioprotector) to either treat or prevent tissue lesions caused due to sporadic transudation of cytotoxic poison for topoisomerase II (represented by anthracyclines, etoposide, teniposide, mitoxantrone daunorubicin, doxorubicin, etc.), medicinal remedies and pharmaceutical set of the same indication. It is, also, suggested to apply the method to treat or prevent tissue lesions caused by sporadic transudation of topoisomerase II poison. BisdioxopiperazineICRF-187 has impact due to catalytic inhibiting topo II. Signs for possible transudation of topoisomerase II poison (of local toxicity) usually include the availability of acute pain, erythema, development of ulcerations in area of transudation; due to the action of ICRF-187 the quantity of wounds is reduced, or the development of side effects is not observed.
EFFECT: higher efficiency of therapy.
59 cl, 12 dwg, 13 ex, 10 tbl
FIELD: organic chemistry, medicine, pharmacy.
SUBSTANCE: invention relates to derivatives of adamantane of the general formula:
wherein m = 1 or 2; each R1 represents independently hydrogen atom; A represents C(O)NH or NHC(O); Ar represents the group:
wherein X represents a bond, oxygen atom or group CO, (CH2)1-6, CH=, O(CH2)1-6, O(CH2)2-6O, O(CH2)2-3O(CH2)1-3, CR'(OH), NR5, (CH2)1-6NR5, CONR5, S(O)n, S(O)nCH2, CH2S(O)n wherein n = 0, 1 or 2; R' represents hydrogen atom; one of R2 and R3 represents halogen atom, nitro-group, (C1-C6)-alkyl; and another is taken among R2 and R3 and represents hydrogen or halogen atom; either R4 represents 3-9-membered saturated or unsaturated aliphatic heterocyclic ring system comprising one or two nitrogen atoms and oxygen atom optionally being heterocyclic ring system is substituted optionally with one or more substitutes taken independently among hydroxyl atoms, (C1-C6)-alkyl, (C1-C6)-hydroxyalkyl, -NR6R7, -(CH2)rNR6R7; or R4 represents 3-8-membered saturated carbocyclic ring system substituted with one or more substitutes taken independently among -NR6R7, -(CH2)NR6R7 wherein r = 1; R5 represents hydrogen atom; R6 and R7 each represents independently hydrogen atom or (C1-C6)-alkyl, or (C2-C6)-hydroxyalkyl group eliciting antagonistic effect with respect to R2X7-receptors. Also, invention describes a method for their preparing, pharmaceutical composition comprising thereof, a method for preparing the pharmaceutical composition and their applying in therapy for treatment of rheumatic arthritis and obstructive diseases of respiratory ways.
EFFECT: improved method for preparing and treatment, valuable medicinal properties of compounds.
13 cl, 88 ex
SUBSTANCE: at performing curative endoscopy one should apply pneumoapplication of granulated sorbent - diovine at the quantity of 0.2 g, the pressure being 15 atm. at the distance of 1.5 cm against the defect onto the surface of bleeding rupture of gastric mucosa. Diovine's coarse-grained structure enables to keep the integrity of mucous-bicarbonate barrier due to providing normal vapor exchange and moisture medium in the defect. Moreover, diovine's antimicrobial action helps to suppress gram-positive and gram-negative microflora that enables to shorten terms for defects healing and decrease the frequency of repeated hemorrhages.
EFFECT: higher efficiency of therapy.
FIELD: medicine, pharmacy.
SUBSTANCE: invention proposes a medicinal formulation consisting of a core and the stomach-dissolving envelope. The core comprises trimetazidine dihydrochloride as an active component, and starch, mannitol, povidone, magnesium stearate, croscarmelose and microcrystalline cellulose as accessory substances. The envelope comprises hydroxypropylmethylcellulose, polyethylene glycol, titanium dioxide, magnesium stearate and acid red as a dye. Also, invention describes a method for making the trimetazidine medicinal formulation. Trimetazidine tablets show high mechanical strength in the low pressing strength (3.5-5 kH). The composition of the medicinal formulation provides releasing 80% of trimetazidine for 30 min.
EFFECT: improved and valuable properties of formulation.
3 cl, 1 tbl, 1 ex
FIELD: medicine, neurology, pharmacy.
SUBSTANCE: invention proposes using levetiracetam and the corresponding levetiracetam-base pharmaceutical composition used in treatment of bipolar disorders, mania and migraine. Also, invention relates to a pharmaceutical composition based on levetiracetam and at least one inhibitor of GABA type A neuronal receptors that is used in treatment of epilepsy, alcohol withdrawal syndrome, tremor, bipolar disorders, obsessive-compulsive disorder, panic state, depression, headache, pain, ischemia and head trauma, to corresponding methods for treatment, to a method for selective enhancing the therapeutic effect of inhibitors of GABA type A neuronal receptors, to a method for treatment of patient with inhibitor of GABA type A neuronal receptors involving the combined administration of indicated inhibitor of GABA type A neuronal receptors with levetiracetam. Invention shows the possibility for using levetiracetam for treatment of chronic and neuropathic pain in lower doses as compared with doses causing secondary effects, and shows its property to enhance activity of inhibitor of GABA type A neuronal receptors.
EFFECT: improved and valuable medicinal properties of agent.
18 cl, 18 tbl, 7 ex
FIELD: medicine, otorhinolaryngology.
SUBSTANCE: invention relates to substances causing fresh and relieving sense in mouth cavity, pharynx and respiratory ways, to compositions containing these compounds and to using these compounds. Compounds represent acyclic ethers. Using proposed compositions allows eliminating bitter taste of medicines, they are stable and their effect in using is more continuous.
EFFECT: improved and valuable properties of agent.
18 cl, 4 ex