Benzoic acid, benzoic acid derivatives and heteroaryl carboxylic acid conjugates of hydromorphone, prodrugs, methods for producing and using them

FIELD: medicine.

SUBSTANCE: invention refers to a prodrug composition for treating diseases, disorders or conditions mediated by opioid binding to opioid receptors, containing a conjugate representing 3,6-diaspirin-hydromorphone in a pharmaceutically effective amount, and a biologically acceptable carrier. The invention also refers to a method of treating a patient suffering a disease, disorder or condition mediated by opioid binding to opioid receptors.

EFFECT: composition manifests improved bioavailability, lesser variability in an oral pharmacokinetic profile, lower peak plasma concentration and a lower probability of overdosage as compared to unconjugated hydromorphone.

12 cl, 21 dwg, 2 tbl, 7 ex

 



 

Same patents:

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to therapeutic or preventive means in case of disease(s) of biliary tracts, which are caused or are aggravated by sphincter of Oddi contraction. As effective component, claimed means contains compound, presented by general formula

.

In formula (I) double line, which contains from dotted line and solid line, represents double bond or single bond, R1 represents C4-C7-cycloalkylalkyl, R2 represents linear or branched C1-C5-alkyl, and B represents - CH=CH-.

EFFECT: invention also relates to compound of formula (I) and to method of treatment or prevention in case of disease(s) of biliary tracts, which are caused or intensified by sphincter of Oddi contraction.

6 cl, 1 dwg, 1 ex

FIELD: biotechnologies.

SUBSTANCE: conjugate represents benzoate-hydrocodone that has the following structure: benzoate-hydrocodone (Bz-HC). Invention also pertains to the application of pharmaceutical compound for obtaining the drug for curing the patient with illness, disease or condition mediated by opioid binding to the opioid receptors of the patient.

EFFECT: improvement of medical treatment efficiency or prevention of drug abuse, drug withdrawal symptoms or pain relief.

10 cl, 11 ex, 4 tbl, 20 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention declares a compound of structural formula (I) or its pharmaceutically acceptable salt, solvate or hydrate wherein: X is phenol opiate wherein a hydrogen atom of a hydroxyl phenol group of substituted by a covalent bond with -C(O)-Y-(C(R1)(R2))n-N-C(R3)(R4);Y is -NR5-, R5 is (C1-6)alkyl; n is equal to 2 or 3, each of R1 and R2 is independently hydrogen, alkyl or substituted alkyl; R3 is hydrogen or methyl; R4 is a residue of L-amino acid or a residue of their N-acyl derivatives, as well as Hydromorphone 3-(N-methyl-N-(2-N'-acetylarginine amino)ethyl carbamate, or their pharmaceutically acceptable salt. What is also specified is a method for preparing the compound of formula (I) or its pharmaceutically acceptable salt.

EFFECT: what is declared is a pharmaceutical composition controlling phenol opiate release and a method of pain management in a patient in need thereof involving the introduction of an effective amount of the composition.

19 cl, 20 ex, 12 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to chemical-pharmaceutical industry, particularly a method for making the oxymorphone derivative naltrexone being an opiate antagonist by naltrexone processing by diazomethane in the presence of palladium acetate.

EFFECT: method eliminates using hardly accessible and expensive parent compounds, and it is characterised by ease of implementation.

3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of general formula in which R1 represents C1-C10-alkyl with a straight or branched chain, optionally substituted by an aromatic ring, or -(CH2)nX(CH2)n- in which each n is equal to an integer from 0 to 2, X represents O, S, NH and where R2 represents H or C1-C6-alkyl with the straight or branched chain. Also, the invention refers to application of buprenophine derivative esters on a hydroxyl group of phenol for treating opiate dependences and/or moderate to strong pain, and to application as an agent releasing a therapeutic amount of buprenophine into a human body.

EFFECT: preparation of new buprenophine derivatives a hydroxyl group of phenol for treating opiate dependences and/or moderate to strong pain.

20 cl, 7 dwg, 1 tbl, 11 ex

FIELD: chemistry.

SUBSTANCE: disclosed method of determining opium alkaloids involves extraction sample preparation carried out using a water-acetonitrile mixture with ratio of water to acetonitrile ranging from 38:12 to 42:8, as well as analysis of the obtained extract through high-performance liquid chromatography, carried out at wavelength 210 and 220 nm. The rate of extraction of alkaloids can be increased by adding mineral acid, for example orthophosphoric acid, to the extracting water-acetonitrile mixture.

EFFECT: shorter analysis time and fewer operations while preserving the degree of extraction of alkaloids.

3 cl, 9 dwg, 1 ex

The invention relates to a method for producing derivatives of morphinan, which are intermediate compounds for obtaining derivatives of 14-hydroxymorphinone, which, in turn, are used to obtain opiate antagonists derived Oxymorphone

The invention relates to organic chemistry, specifically to a method for producing esters of N-substituted 14-hydroxymorphinone that are important narcotic analgesic and/or antagonistic means - opiate receptor blockers prolonged action

The invention relates to organic chemistry, particularly to esters of N-substituted 14-hydroxymorphinone that are important narcotic analgesic and/or antagonistic means - opiate receptor blockers prolonged action and to methods for their preparation

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula

,

possessing properties of binding with delta opioid receptors. In formula I R1 is selected from the group, consisting of phenyl, pyridinyl and thiazolyl, with R1 being optionally substituted with one or two substituents, independently selected from the group, consisting of C1-4alkoxy, fluorine atom, chlorine atom, bromine atom and cyanogroup; in addition, R1 is optionally substituted with di(C1-4alkyl)aminocarbonyl; Y represents O, S, H3, vinyl, ethinyl or S(O); R2 represents a substituent, selected from the group, consisting of hydrogen, C1-4alkyl, C1-4alkoxy, C1-4alkylthio, fluorine atom, chlorine atom, bromine atom and hydroxy; Ra represents hydrogen or methyl; R3 is selected from the group, consisting of pyrrolidin-2-ylmethyl; pyrrolidin-3-ylmethyl; piperidin-2-ylmethyl, piperidin-3-ylmethyl, piperidin-4-ylmethyl, piperidin-2-ylethyl, piperidin-3-ylethyl, piperidin-4-ylethyl, pyridine-4-yl-(C1-2)alkyl, azetidin-3-ylmethyl; morpholin-2-ylmethyl, morpholin-3-ylmethyl, imidazolylmethyl, thiazolylmethyl, (amino)-C3-6cycloalkyl, 3-hydroxy-2-aminopropyl, 8-azabicyclo[3.2.1]octanyl, 1-azabicyclo[2.2.2]octanyl, guanidinylethyl, 4-(imidazol-1-yl)phenylmethyl, 2-(methylamino)ethyl, 2-diethylaminoethyl, 4-diethylaminobut-2-yl, piperidin-3-yl, piperidin-4-yl and pyrrolidin-3-yl; with piperidin-3-yl being optionally substituted on a carbon atom with phenyl; with pyrrolidin-2-yl in pyrrolidin-2-yl-methyl, pyrrolidin-3-yl, piperidin-3-yl and piperidin-4-yl being optionally substituted on a nitrogen atom with methyl, phenylmethyl, phenethyl or methylcarbonyl.

EFFECT: compounds can be used in the treatment of pain, induced by diseases or conditions, such as osteoarthritis, rheumatoid arthritis, migraine, burn, fibromyalgia, cystitis, rhinitis, neuropathic pain, idiopathic neuralgia, toothache, etc.

24 cl, 3 tbl, 19 ex

Transdermal plaster // 2553350

FIELD: medicine.

SUBSTANCE: group of inventions relates to medicine. Described is matrix layer, suitable for application in plaster for transdermal delivery, aimed at introduction of biologically active compounds, which includes phosphate compound of tocopherol and polymer carrier. Also described is transdermal plaster and method of its production.

EFFECT: plaster makes it possible to efficiency introduce biologically active compounds.

48 cl, 15 tbl, 13 dwg, 12 ex

FIELD: medicine.

SUBSTANCE: suppositories, containing uniformly distributed in one suppository recombinant human interferon-alpha-2b in an amount of 400000-600000 IU and immunoglobulins IgA, IgM and IgG in an amount of 0.1-0.3 g, are additionally rectally introduced as the second medication to an adult patient in case of the long-term introduction of an opioid-containing medication. The dose constitutes 2-3 suppositories 2-3 times per day with the reduction of the daily dose by 1-3 suppositories in case of the reduction of pain sensation to 2-3 points by a ten-point scale and expressed sedation. If pain sensation increases to 6-8 points by the ten-point visual analogue scale, the daily dose is increased by 1-3 suppositories.

EFFECT: application of the claimed method makes it possible to ensure the prevention of the opioid dose increase and an increase of the level of antibodies to interferon-alpha in the patients' blood serum in case of the long-term application of opioids.

5 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a therapeutic agent for treating or preventing neuropathic pain containing active ingredients in the form of a cyclohexane derivative presented by the following formula, or its pharmaceutically acceptable salt, and a calcium channel α2δ ligand which represents pregabalin or gabapentin.

EFFECT: therapeutic agent possesses the synergistically increased analgesic action in a dose which prevents any side effects of the calcium channel α2δ ligand, and which prevents any side effects of the agent on the central nervous system .

3 cl, 5 dwg, 5 tbl, 4 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to organic chemistry, namely to pyrazine derivatives of formula I, as well as to their enanthiomers, diastereomers and pharmaceutically acceptable salts, wherein R1 is specified in a group consisting of ii) pyridinyl optionally having one substitute specified in a group consisting of C1-4alkoxy and cyano; and iii) pyrimidin-5-yl; or R1 optionally represents methoxymethyl, when Y represents ethinyl; Y represents ethinyl or a bond; R2 represents phenyl, benzofuranyl, 2,3-dihydrobenzofuranyl, benzo[1,3]dioxol-5-yl, indolyl or pyridinyl substituted by methyl, phenyl has one to two substitutes independently specified in a group consisting of C1-4alkyl, C1-4alkoxy, fluorine, chlorine, cyano, cyanomethyl, difluoromethyl, trifluoromethyl and hydroxy; or R2 represents phenyl having one C1-4alkylcarbonylamino or 1H-imidazol-1-yl substitute; X represents O or CH2; L is absent, and R3 represents 4-aminocyclohexyl, or L represents methylene, while R3 is specified in a group consisting of i) pyrrolidin-2-yl; ii) 1-aminoeth-1-yl; and iii) 1-aminocyclopent-1-yl; or R3 is combined into one cycle with L nitrogen atom to which L is attached to form piperazinyl. Besides, the invention refers to specific compounds, a pharmaceutical compound based on a compound of formula I, a method of treating pain and some neurodegenerative diseases.

EFFECT: there are produced new pyrazine derivative effective in treating pain and some neurodegenerative diseases.

21 cl, 3 tbl, 13 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to organic chemistry, namely to a compound of formula (I) and its isomers, using them for treating a condition associated with P2X3 activity, to a pharmaceutical composition based on the compound of formula (I) or its isomers, and to a method of treating.

EFFECT: what is prepared is the new heterocyclic compound possessing the effective biological properties.

16 cl, 1 tbl, 6 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to pharmaceutics, namely to pharmaceutical drug forms, containing poly-ε-caprolactone, and methods of obtaining them, an application and methods of treatment with their application.

EFFECT: application of a poly-ε-caprolactone matrix makes it possible to provide properties, constraining from abuse (such as resistance to crushing or grinding).

32 cl, 14 dwg, 14 ex, 14 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: in formula R1 is H or (1-6C alkyl); R2 represents NRbRc, (1-4C)alkyl, (1-4C)fluoroalkyl, CF3, (1-4C)hydroxyalkyl, -(1-4Calkyl)hetAr1, -(1-4Calkyl)NH2, -(1-4C alkyl)NH(1-4Calkyl), -(1-4Calkyl)N(1-4Calkyl)2, hetAr2, hetCyc1, hetCyc2, phenyl substituted where applicable by NHSO2(1-4Calkyl) or (3-6C)cycloalkyl, substituted where applicable by (1-4C alkyl), CN, OH, OMe, NH2, NHMe, N(CH3)2, F, CF3, CO2(1-4C alkyl), CO2H; C(=O)NReRf or C(=O)ORg; Rb is H or (1-6C alkyl); Rc represents H, (1-4C)alkyl, (1-4C)hydroxyalkyl, hetAr3 or phenyl, wherein the above phenyl is substituted where applicable by one or more substitutes independently from halogen, CN, CF3 and -O(1-4C alkyl); Re represents H or (1-4C)alkyl; Rf represents H, (1-4C)alkyl or (3-6C)cycloalkyl; Rg represents H or (1-6C)alkyl; X is absent or represents -CH2-, -CH2CH2-, -CH2O- or -CH2NRd; Rd represents H or (1-4C alkyl); R3 represents H or (1-4C alkyl); and n is equal to 0-6. The radical values NRbRc, Y, hetAr1, hetAr2, hetAr3, hetCyc1, hetCyc2, NReRf, R4 are specified in the patent claim. The invention also refers to a pharmaceutical composition containing the above compounds, to a method of treating Trk kinase mediated diseases and conditions, such as pain, cancer, inflammation, neurodegenerative disease, Typanosoma cruzi infection, osteolytic disease, and to a method of preparing the above compounds.

EFFECT: invention refers to new derivatives of pyrazolo[1,5-a]pyrimidines possessing an inhibitory activity on tropomyosin-related kinases (Trk).

42 cl, 1 tbl, 105 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed are: a peroral pharmaceutical composition with an instant release for treating pain in patients or for titration of a dose for the patients, suffering from pain, which contains at least oxicodon or its pharmaceutically acceptable salt and naloxon or its pharmaceutically acceptable salt in an approximate weight ratio oxicodon or its pharmaceutically acceptable salt: naloxon or its pharmaceutically acceptable salt 2:1 (versions), its application for obtaining medication for titration of the dose for the patients, suffering from pain, its application for obtaining medication for treatment of breakthrough pain, a method of titration of the dose in the patient, suffering from pain, and a method of treating breakthrough pain.

EFFECT: achievement of the claimed results with absence of undesirable side effects of opioid is demonstrated, with levels of naloxon in the blood plasma being extremely low, bioavailability of oxicodon constituting 96.3 or 99.2%, and tablets being stable in storage.

30 cl, 9 dwg, 15 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to buprenorphine analogues of formula , where R1 is selected from -(C1-C10)alkyl, -(C2-C12)alkenyl, -(C3-C12)cycloalkyl, ((C3-C12)cycloalkyl)-(C1-C6)alkyl-; any of which is optionally substituted with 1 or 2 substitutes selected from OH and -(5-12-member)heterocycle, wherein at least one carbon atom is substituted with a nitrogen heteroatom; R2 and R8 each independently is hydrogen, -(C1-C10)alkyl, -(C2-C12)alkenyl, -(C2-C12)alkynyl, -(C3-C12)cycloalkyl, -(5-9-member)heteroaryl, where in the 5-9-member heteroaryl, at least one carbon atom is substituted with a nitrogen, oxygen or sulphur heteroatom, phenyl and naphthyl; any of which is optionally substituted with one or two substitutes selected from OH, halo, -C(halo)3, -(C1-C6)alkyl, phenyl, NH2, CN, OR4 and COOR7; at least one of R2 or R8 is not hydrogen; R3a and R3b are independently selected from hydrogen and -(C1-C6)alkyl; R4 is selected from -(C1-C6)alkyl, -C(halo)3 and phenyl; R7 is hydrogen; X is selected from (C1-C6)alkoxy or OH; Z is (CH2)m; Y is (CH2)n-CH or a direct bond, under the condition that when Y is a direct bond, R8 is absent; m equals 1 and n equals 0. The invention also relates to a pharmaceutical composition which modifies opioid receptor function and is intended to treat pain, which contains compounds of formula I, a method of preparing said composition, a method of modulating an opioid receptor and a method of treating pain.

EFFECT: compounds of formula I as opioid receptor function modulators.

37 cl, 11 dwg, 7 tbl, 6 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to thermoformed pharmaceutical dosage form having a minimum tensile strength of 300 N; the above dosage form contains an opioid, a free physiologically acceptable carboxylic acid in an amount from 0.1 to 5.0 wt %, at total weight of the pharmaceutical dosage form and polyalkylene oxide having a minimum average molecular weight Mm of 500,000 g/mole. Carboxylic acid is specified in a group consisting of maleic acid, fumaric acid, glutaric acid, malonic acid and citric acid. The opioid is specified in a group consisting of oxymorphone, oxycodone, hydromorphone and their physiologically acceptable salts. The pharmaceutical dosage form can be packaged.

EFFECT: pharmaceutical dosage for according to the invention is characterised by the improved storage stability.

14 cl, 11 tbl, 9 ex

Up!