Method of prophylaxis of post-traumotomic pain syndrome in oncosurgery

FIELD: medicine.

SUBSTANCE: for the prevention of post-thoracotomy pain syndrome (hereinafter - PTPS) in oncosurgery a day before the surgery, anticonvulsant pregabalin is administered orally 75 mg 2 times/day and 75 mg 2 hours before the operation. Then, an epidural catheter is performed on the operating table, through which a three-component mixture is infused throughout the operation: ropivacaine 3 mg/ml+fentanyl 4 mcg/ml+epinephrine 2 mcg/ml at a rate of 5-15 ml/h. Induction of anesthesia is intravenously: fentanyl 0.00004±0.00002 mg/kg, ketamine 0.29±0.13 mg, propofol 0.56±0.31 mg/kg, rocuronium bromide 0.68±0.14 mg/kg. Maintenance of anesthesia: sevoflurane inhalation 0.6-1 MAK in an oxygen-air mixture (FiO2 0.3-0.8), fentanyl 0.00004±0.00002 mg/kg/h, ketamine 0.0013±0.0002 mg/kg/hour. 40 minutes before the end of the operation, nefopam is administered with 20 mg IM. In the postoperative period, infusion is performed in the epidural space: ropivacaine 2 mg/ml+fentanyl 4 mcg/ml+epinephrine 2 mcg/ml, injection rate 4-6 ml/h for 2 days. Then, the mixture reduces the concentration of ropivacaine to 0.2% and continues infusion to 5-7 days, at a rate of 4-6 ml/h. At occurrence of the first complaints on painful sensations prescribe nefopam of 20 mg im/m and continue its appointment in a dose of 20 mg 2 times a day for 5 days and lornoxicam 8 mg intravenously - 2 times/day and pregabalin 75 mg orally - 2 times/day for 5 days. In case of ineffectiveness of this therapy, morphine is prescribed 10 mg IM.

EFFECT: invention allows to reduce the frequency of development of acute PTPS, its intensity, to reduce the postoperative need for opioid analgesics and to reduce the frequency of development of chronic PTPS.

2 ex



Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to a novel chemical substance - 4,10-bis((±)-5-benzoyl-2,3-dihydro-1H-pyrrolo[1,2-a]pyrrole-1-carbonyl)-2,6,8,12-tetraacetyl-2,4,6,8,10,12-hexaazatetracyclo[5,5,0,03,11,05,9]dodecane The invention also relates to a method of its obtaining, which consists in the acylation of 2,6,8,12-tetraacetyl-2,4,6,8,10,12- hexaazatetracyclo [5,5,0,03,11,05,9]dodecane by chloranhydride 5-benzoyl-2,3-dihydro-1H-pyrrolo[1,2-a]pyrrole-1-carboxylic acid.

EFFECT: novel compound, which has analgetic activity, is obtained.

2 cl, 1 tbl, 2 ex

FIELD: chemistry.

SUBSTANCE: invention relates to organic chemistry and specifically to novel heterocyclic compounds of general formula (I) or enantiomers, diastereomers or pharmaceutically acceptable salts thereof, where Y is: phenyl or a heteroaryl selected from thiazolyl, pyridyl, pyrimidinyl, 1,3,5-triazinyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl and 1,3,4-thiadiazolyl; wherein the phenyl or heteroaryl is optionally substituted with one substitute selected from fluorine, chlorine, bromine, iodine, C1-4alkyl, trifluoromethyl, C1-4alkoxy, C1-4alkylthio, nitro and cyano; r=1-2; R2 is absent or is an oxo-group; Z is: (a) phenyl substituted with NRaRb; where Ra is: H or C1-4alkyl; where Rb is: C1-4alkyl, cycloalkyl, phenyl, furanylmethyl, or phenyl(C1-2alkyl); and wherein the phenyl or the furanyl are optionally substituted with iodine; alternatively, Ra and Rb are taken together with the nitrogen atom to which they are bonded to form a 5-8 member heterocyclyl, which is optionally condensed to a benzene ring; (b) biphenyl-3-yl or biphenyl-4-yl; where the interior phenyl ring, attached to the carbonyl in formula (I) is optionally substituted with a fluorine atom; and where the terminal phenyl ring is optionally substituted with a substitute selected from trifluoromethyl, C1-4alkoxy, chlorine, dichloro, fluorine, and iodine; (c) phenyl substituted with a substitute selected from C5-8cycloalkyl, -NHC(=O)cyclohexyl, phenyloxy, phenylcarbonyl, phenyl(C1-3)alkyl, phenyl(C1-3)alkoxy, pyrrolyl, pyrazolyl, imidazolyl, isoindol-2-yl-l,3-dione, 2,3-dihydro-isoindol-2-yl; l-(tert- butoxycarbonyl)piperidin-4-yloxy, and 1-(tert-butoxycarbonyl)piperidin-4-yl; (d) phenyl substituted with 1-2 substitutes independently selected from: C1-6alkyl, C1-4alkoxy, iodine, chlorine and nitro; (e) phenyl(C1-2)alkyl; where the phenyl is optionally substituted with 1 or 2 substitutes independently selected from iodine, fluorine, C1-6alkyl, phenyl and NRcRd; where Rc: H or C1-4alkyl; where Rd is: C1-4alkyl or C1-6cycloalkyl(C1-4)alkyl; and where the C1-2alkyl of phenyl(C1-2)alkyl is optionally substituted with phenyl; (f) phenyl(C2-4)alkenyl; where the phenyl is optionally substituted with a substitute selected from C1-4alkyl, C1-4alkoxy, trifluoromethyl, trifluoromethylthio and phenyl; (g) naphthyl; where the naphthyl is optionally substituted with one C1-4alkoxy substitute; (h) fluorenyl or xanthenyl; where the fluorenyl or xanthenyl is optionally substituted with an oxo group; (i) C5-8cycloalkyl; where the C5-8cycloalkyl is optionally substituted with one C1-6alkyl substitute; (j) benzene ring-condensed C5-8cycloalkyl or benzene ring-condensed C5-8cycloalkyl(C1-4)alkyl; where said C5-8cycloalkyl fragment is optionally substituted with 1-4 methyl groups; (k) bicyclo[2.2.2]octyl-1-yl; where the bicyclo[2.2.2]octyl-l-yl is optionally substituted with C1-6alkyl; (1) a heteroaryl or benzene ring-condensed heteroaryl selected from benzooxazolyl, quinolinyl, benzimidazolyl, pyridinyl, indolyl, thienyl, furanyl, pyrazolyl, oxazolyl, benzothienyl and benzofuranyl; where the heteroaryl or benzene ring-condensed heteroaryl is optionally substituted with 1 or 2 substitutes independently selected from C1-4alkyl, trifluoromethyl, C5-8cycloalkyl, phenyl, phenyl(C1-2)alkoxy, phenyl(C2-4)alkynyl and dichlorophenoxy; and where the phenyl substitute in the heteroaryl is further optionally substituted with C1-4alkyl, C1-4alkoxy or trifluoromethyl; (m) l,5-diphenyl-lH-pyrazol-3-yl; where the pyrazol-3-yl is optionally substituted with a methyl group; and where each of the phenyl groups of the 1,5-diphenyl substitutes is also optionally substituted with substitutes selected from chlorine, dichloro or aminosulphonyl; (n) 1,2,3,4-tetrahydroquinolin-6-yl; where the 1,2,3,4-tetrahydroquinolin-6-yl is optionally substituted with phenyl or trifluoromethyl-substituted phenyl; and (o) benzene ring-condensed heterocyclyl(C2-4)alkenyl; where the benzene ring-condensed heterocyclyl is attached to the C2-4alkenyl via the benzene ring; and where benzene ring-condensed heterocyclyl is further optionally substituted with C5-6cycloalkyl; taking into account constraining conditions indicated in claim 1. The invention also relates to a pharmaceutical composition based on the compound of formula (I), a method of producing said pharmaceutical composition, a method of treating said pathological conditions and use of the compound of formula (I).

EFFECT: obtaining novel heterocyclic compounds having MGL inhibiting activity.

21 cl, 5 tbl, 11 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutical industry and represents a pharmaceutical composition for control of pain accompanying individual's joint diseases containing hyaluronic acid, which is cross-linked by cycling a double bond in a group of cinnamic acid in partially amidated hyaluronic acid presented by formula (1) to form a cyclobutane cycle, wherein in the above formula, Ar represents a phenyl group, n is equal to an integer 2 or 3; HA represents a carboxy residue of hyaluronic acid, and m represents a relation of amidation of hyaluronic acid to all the carboxyl groups and is equal to 3-50% in relation to all the carboxyl groups, and a pharmaceutically acceptable carrier, wherein the pharmaceutical composition represents a product for injection, wherein the pharmaceutical composition represents the product for injection, wherein the amount of the cross-linked hyaluronic acid makes 1 wt % at the total amount of the product for injection, wherein a single dose of the product for injection makes 2-3 ml, wherein the pharmaceutical composition represents a single-use preparation, which is administered every 13 weeks and more.

EFFECT: invention provides the extremely long analgesic action after the single administration, earlier onset of the analgesic action.

15 cl, 1 dwg, 5 tbl, 1 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutical industry, namely to a method for preparing a medicinal product possessing choleretic activity. The medicinal product possessing choleretic activity and prepared by extracting an elevated part of Lomatogonium carinthiacum in 96% ethanol twice at room temperature, them in 40% ethanol with an extractant added in an amount equal to a discharged one, twice; the filtered aqueous-alcoholic extracts are combined; the extraction cake is extracted in purified water; the aqueous extract is filtered; the aqueous residues of the aqueous-alcoholic extracts are combined with the aqueous extract, concentrated, dried in a vacuum drying cabinet to produce the dry extract in the certain environment.

EFFECT: medicinal product prepared as described above possesses the evident choleretic activity.

11 tbl, 3 ex

FIELD: medicine.

SUBSTANCE: using a polyphenolic complex produced by extracting milled ash berry in 40% ethanol, condensing the alcohol-water extract, adding 95% ethanol, centrifuging the residue, filtering and condensing the supernatant in the certain environment, as an agent possessing anti-inflammatory action.

EFFECT: polyphenolic complex possesses pronounced anti-inflammatory action.

1 dwg, 9 tbl, 7 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to pharmaceutical composition, containing compound of formula or for prevention or treatment of diseases, associated with oxidative stress, selected from group, consisting of MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke episodes), MERRF syndrome (myoclonic epilepsy with ragged red fibres) or Kearns-Sayre syndrome, arrhythmia, cardioplegia or myocardium infarction. in formula (1) na stands for 1 or 2, Aa represents 5-membered heteroaryl or heterocycle, each of which has 2 heteroatoms, selected from N, O and S, Rla represents R5a-Xa-Ba-X′a-, Ba represents direct bond, Xa and X′a independently on each other represent direct bond or -OC(O)-, R5a represents hydrogen or 6-9-membered monocyclic or condensed cyclic heterocycle or heteroaryl, each of which has from 1 to 3 heteroatoms, selected from N, O and S, and is optionally substituted with oxo or C1-C6-alkyl, R2a represents -(CR8aR9a)pa-Ya-R7a, pa stands for number from 0 or 1, Ya represents direct bond or -O-, R7a represents hydrogen or phenyl, R3a, R8a, R9a, R10a represent hydrogen, R4a represents -(CH2)pa-Da-R10a-, Da represents C5-cycloalkyl or 6-membered heterocycle, which has 1 heteroatom, selected from N, S and O. Radical values for formula (2) are give in invention formula.

EFFECT: obtaining compositions for prevention or treatment of diseases, associated with oxidative stress.

19 dwg, 5 tbl, 3 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing 9-aryl-6,8,20-trioxa-13-azapentacyclo-[,10.02,7.014,19]heneicosa-9,14,16,18-tetraene-11,12,21-triones (IIa-d), which includes reacting 3-aroyl-1H-pyrrolo[2,1-c][1,4]benzoxazine-1,2,4-triones (Ia-d) with 3,4-dihydro-2H-pyran in a medium of an inert aprotic solvent, followed by separation of the end products. In general formula (I) Ar=Ph (a, d), C6H4Br-4 (b), C6H4OMe-4 (c), R=H (a-c), Cl (d).

EFFECT: obtaining 9-aryl-6,8,20-trioxa-13-azapentacyclo-[11,8,0,01,10,02,7,014,19]heneicosa-9,14,16,18-tetraene-11,12,21-triones.

2 cl, 1 tbl, 5 ex

FIELD: chemistry.

SUBSTANCE: invention refers to a new compound, namely to 2-[(2-methylphenyl)imino]-9-oxo-7-phenyl-8-(3-phenyl-2-quinoxalinyl)-1,6-dioxaspiro[4,4]none-3,7-diene-3,4-dicarboxylic acid dimethyl ester of formula possessing antinociceptive activity, and a method for producing it consisting in synthesis of 4-(3-phenylquinoxalin-2-yl)-5-phenylfurane-2,3-dione, acetylene dicarboxylic acid dimethyl ester and o-methylphenylisonitrile.

EFFECT: preparing the new compound.

2 cl, 1 tbl, 4 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to compound, represented by the following formula


or its pharmaceutically acceptable salt. In claimed formula each symbol has values, determined in formula of invention. Versions of formula [I] compound and particular compounds are also objects of invention. In addition, invention relates to pharmaceutical composition, ITK inhibitor and means for treatment or prevention of inflammatory diseases, allergic diseases, autoimmune diseases, transplant rejection and other diseases and methods of treating said diseases.

EFFECT: claimed compounds inhibit induced T-cellular kinase (ITK).

32 cl, 86 tbl, 387 ex

FIELD: medicine.

SUBSTANCE: application of a compound of the general formula 1 or its spatial isomers as analgesic means is claimed.

EFFECT: compounds have high efficiency, low toxicity, can be applied in medicine.

4 tbl 8 ex

FIELD: medicine.

SUBSTANCE: anaesthetising patients with chronic pain syndrome undergoing a cyclophotocoagulation surgery involves the intravenous administration of the hormonal preparation dexamethasone in a dose of no more than 8 mg followed by the anxiolytic droperidol in a dose of no more than 2.5 mg 5 minutes prior to the operation before the peribulbar anaesthesia. A peripheral block in the form of the peribulbar anaesthesia involving administration of no more than 6 ml of a local anaesthetic follows. At the moment the surgical procedure starts, benzodiazepin, e.g. diazepam, is administered in a dose of no more than 5 mg.

EFFECT: achieving adequate anaesthesia in the given category of patients by blocking all the links of a pathological pain chain.

1 ex

FIELD: medicine.

SUBSTANCE: dexamethasone 8 mg and ketoprofen 100 mg is administered intravenously once prior to the operation. A lumbar plexus is blocked in a combination with a parasacral block and inserting perineural catheters to administer weak 0.2% Ropivacaine, local anaesthetic 20 ml. Paracetamol 1,000 mg is administered intravenously 30 minute before the operation is completed. After the operation is completed, the perineural catheter of the lumbar plexus is used to infuse 0.2% Ropivacaine 300 ml at 6-8 ml/hour for 4-5 days. Ketoprofen 100 mg is administered intramuscularly twice a day for 3 days. Through the perineural catheter of the parasacral plexus, 0.2% Ropivacaine 10 ml is administered twice every 12 hours.

EFFECT: method provides the adequate anaesthesia in the given category of patients by having an effect on primary pain components, as well as ensures the continuous and prolonged anaesthesia both intra-, and postoperatively, prevents the stable and chronic pain syndrome and the motor block of the extremities, reduces a rate of toxic complications.

1 ex

FIELD: medicine.

SUBSTANCE: preanaesthetic medication preceding gynaecological surgeries under general anaesthesia is ensured by prescribing diazepam 10mg, nefopam 10mg and ketoprofen 100mg intramuscularly 30-40 min before the surgery.

EFFECT: method enables reaching the sedative and analgesic effect of the preanaesthetic medication by the complementary action of preparations with no undesired side effects, requiring no time consumption and expensive equipment.

3 tbl, 2 ex

FIELD: chemistry.

SUBSTANCE: as active component pharmaceutical composition contains dihydrochloride of 9-(2-morpholine ethyl)-2-(4-fluorophenyl)imidazo[1,2-α]benzimidasol, and as additional substances - fillers, binding, sliding and film coatings, in quantities, given in the invention formula. Composition can be made in form of solid medication form, mainly in form of tablets and capsules.

EFFECT: obtained solid medication forms satisfy the requirements of the State Pharmacopoeia.

7 cl, 2 dwg, 3 tbl, 14 ex

FIELD: medicine.

SUBSTANCE: at the initial stage of the intraoperative period, immediately before the local anaesthesia and the femoral artery puncture, ketorolac tromethamine is administered intravenously as an analgesic, and propofol as a sedative agent. Ketorolac tromethamine is administered in a dose of 15-75 mg, while propofol is administered in a dose of 50-250 mg.

EFFECT: method prevents developing pain and psychoemotional responses caused by the given interventions, including postoperatively by the fast development of the adequate analgesic effect accompanied by the controlled sedation level.

1 tbl, 10 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to organic chemistry, namely to benzimidazole derivatives of general formula (I) and to their pharmaceutically acceptable salts, mixed stereoisomers and enantiomers, wherein R1 is L1C(O)OL2C(O)OT; R2 is unsubstituted C1-C10alkyl; L1 is a bond; L2 is unsubstituted C2-C10alkylene; T is C1-C10alkyl. Also, the invention refers to a pharmaceutical composition of the compound of formula (I) and a method of anaesthetising on the basis of using the compound of formula (I).

EFFECT: there are prepared new imidazole derivatives effective as an anaesthetising agent.

15 cl, 9 dwg, 15 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a new compound, namely to (S)-enantiomer of 1'-{[5-(trifluoromethyl)furan-2-yl]methyl}spiro[furo[2,3-f][1,3]benzodioxol-7,3'-indole]-2'(1'H)-one of formula (I), and a method for preparing it which is effective for treating diseases and conditions, such as pain, an intensity of which can be reduced or relieved by modulating potential-dependent sodium channel gatings.

EFFECT: invention refers to the pharmaceutical composition of the above compound, methods of treating and a method of relieving an ion flux through the potassium channel gating in a cell.

10 cl, 5 tbl, 6 dwg, 11 ex

FIELD: biotechnology.

SUBSTANCE: aqueous composition for anaesthesia is proposed, which comprises propofol as an active agent, the PEG-660-12-hydroxystearate as a solubiliser, benzyl alcohol, or chloroethanol or parabens as preservative, the tocopherol and arginine or glycine at a specific content of components wt %. The GABA agonists can be additionally added to the composition, e.g. aminophenyl-butyric acid, local anesthetics such as lidocaine, alpha-2-adrenoceptor agonists such as xylazine. The method is proposed for implementing anaesthesia comprising administering to a patient of an effective amount of the claimed composition.

EFFECT: invention provides low toxicity of dosage form and high efficiency.

5 cl, 3 tbl, 1 ex

FIELD: medicine.

SUBSTANCE: what is involved is infusion therapy with crystalloid solutions at 15 ml/kg of a patient's body weight. That is followed by puncturing and catheterising an epidural space at the level of ThVII-ThVIII according to the standard practice and introducing a test dose of 2% lidocaine 3 ml. If observing no signs of intrathecal introduction of local anaesthetics 10 minutes later, a basic dose containing 0.75-1% naropin 10 ml or 0.25-0.5% marcaine 10 ml and clofelin 3-5 mcg/kg is introduced. Total intravenous anaesthesia follows 20 minutes after pre-medication with atropine 0.01 mg/kg, 1% diphenylhydramine 1 ml and relanium 10 mg and urethral catheterisation. A narcosis is induced with propofol in a dose of 2 mg/kg. Anaesthesia is maintained with propofol 2-4 mg/kg·h. After that, within the first hour following the detoxification, naloxone 12 mg is introduced intravenously; a naloxone measurement rate is supposed to make 0.8 mg/h for 4-5 following hours of general anaesthesia. The repeated introduction of 0.75-1% naropin 6 ml or 0.25-0.5% marcaine 6 ml and clofelin 2-3 mcg/kg into the epidural space is performed 90 minutes later. After the procedure is terminated, and the patient recovers, prolonged epidural analgesia is conducted by introducing 0.2% naropin 10 ml and clofelin 1 mcg/kg into the epidural space every 4 hours for 24-48 hours.

EFFECT: method provides safety of ultrafast opioid detoxification and prolongs the remission in the given category of patients.

1 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to anaesthesiology and resuscitation, and may be used in epidural anaesthesia. That is ensured by administering slowly intravenously a basic dose of the local anaesthetic: 0.2-1% naropin or 0.2-0.5% marcaine, or 1-2% lidocaine; 1% Sol. Nicotini acidi 1% - 0.5-1 ml into the epidural space 10-20 minutes later. After 5-10 minutes, nicotine test results are visually evaluated by determining a clear interface of skin colour - hyperemic and normal - along an axillary line from both sides. The normal skin interface corresponds to the sympathetic block.

EFFECT: method provides higher accuracy and simplification of measuring the sympathetic block.

1 ex

FIELD: medicine.

SUBSTANCE: method involves providing an anaesthetic support with using the preparations: midazolam, fentanyl, propofol by bolus injections and infusions, artificial pulmonary ventilation by gas mixture O2:N2O=1:2 inhalations. Postoperative nausea and vomiting are prevented by intravenous administration of ondansetron 8 mg and dexamethasone 8 mg at the stage of induction, and by intravenous administration of clonidine 0.0016±0.0002 mg/kg/h in infusions or 0.02-0.025 mg in bolus doses up to 0.0016±0.0002 mg/kg after intubation of the trachea within the first hour of operation with having blood pressure and heart rate controlled.

EFFECT: method is safe and high-effective for preventing postoperative nausea and vomiting.

1 ex