Drug treatments for multiple sclerosis
(57) Abstract:The invention relates to medicine, namely to the production of medicines on the basis of [N-methyl-N -/ D-glyukopiranozil/ammonium-9-one-10-Il/acetate] -cycloferon, and can be used for the treatment of multiple sclerosis. The objective of the invention is to create high quality, effective, low-toxic, versatile tools for the treatment of multiple sclerosis. The problem is solved in that the medicinal product containing the active substance and the solvent, as the active substances used, the compound N-methyl-N/a, Dr. glyukopiranozil/ammonium-2-acridin-9-one-10-Il/acetate, and the solvent is water in the following ratio, wt.%:
active substance - 18,0-22,5
water - the rest
5 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-Il/acetate] -cycloferon (application trademark N 93006831/50 from 24.03.93), and can be used for the treatment of multiple sclerosis.Known parenteral form of the medicinal product based on the chemical analogue of cycloferon replaced acridinone composition:
as active substances substituted acridine sodium salt of 10-carboxymethyl-9-acridone structural formula
the water solvent.The tool has not been used for the treatment of multiple sclerosis.Known means at the specified prototype has the following disadvantages: strong irritating and painful action, due to the high pH (9); the risk of necrosis and gemokoagulyatsii; insufficient concentration of the active substance (55 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 extended in the Pharmacopoeia by means of, for example, buffers, complexing agents.During the experiment, we tried to reduce the pH of the dosage form below 8, but this has not led to a positive result.At pH below 8 there was a gradual precipitation of greenexpo acid, which testifies to the impossibility of soy just used glucocorticosteroid hormones (prednisolone, triamcinolone, dexamethasone) (1,2). In order to reduce the side effects of hormonal therapy at the same time appoint etemity.In remission for patients with signs of immunodeficiency appoint Immunostimulants gamma globulin, levamisole, fractional blood transfusion and blood substitutes, preparations of thymus: fluorouracil (timesin), thymalin, taktivin and symptomatic treatment (1,2).The objective of the invention to create high quality, effective, low-toxic, versatile tools for the treatment of multiple sclerosis.The problem is solved in that the medicinal product containing the active substance and the solvent, as the active substances used, the compound N-methyl-N -/ D-glyukopiranozil/ammonium-2-/acridin-9-one-10-Il/acetate structural formula
< / BR>and as a solvent water in the following ratio, wt.active substance 18,0-22,5
water the rest
Currently, biomedical experiments have shown 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 by the applicant was provideservices for vials with a volume of 1.2 and 5 ml, applied to produce the dosage form.To obtain a parenteral dosage form, the applicant used a specified number of greenexpo acid and water for injections and different amounts allowed in the Pharmacopoeia of the N-methylglucamine.Dosage form was obtained by 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 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 again the type of 18.0-22.5 wt.The results of the surveys are large for a single injection. When using vials in 1 ml with a concentration of active substance 45% dosage form low-tech due to the high viscosity and gives infiltrates with parenteral administration of the drug.In 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 (pH of blood 7,3);
in 5-20 times higher concentration of active substance in the solution, allowing to obtain a pronounced therapeutic effect with minimal amounts of administered drug;
the lack of biological impurities (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 the key bring the volume of the solution to 2 l with water for injection, filtered through Millipore and poured into ampoules and vials. The sealed ampoules and autoclave. Vials sealed with rubber stoppers, practicing aluminum caps and autoclave.The results of biomedical research has been proved to be highly effective drugs in the treatment of multiple sclerosis.Here is an example confirming therapeutic activity of the drug.Patient K., 35 years. Diagnosis: multiple sclerosis (multiple sclerosis), spinal form. Sick since January 1987 (November 1986 flu). Disability group II the basic disease. Repeatedly examined and treated in the clinics of nervous diseases of the postgraduate Institute, military medical Academy. Kirov, Sbbmi them. Acad. Pavlov, surveyed all the specialists and all the usual and most modern methods (including NMR-tomography). Underwent a complete examination (at a famous clinic). Treated with hormones, answered, chimes, drugs thymus had no lasting effect. With 20.04. C., after thorough examination held exchange treatment drug cycloferon scheme:
first course: 1 injection of 8 ml of 22.5% solution, 3 days 4 ml 2But intramuscularly 20 ampoules of 2 ml of 22.5% solution of each.On the background of the treatment was a clear improvement in clinical data as subjective improvement in mood, appearance of faith in the healing and objective change for the better the view, the reduction of the nystagmus, the appearance of previously absent abdominal reflexes, a significant reduction of muscle hypertonicity of the lower extremities, gait improvement, writing, speech). Clinical improvement was accompanied by a clear normalization of indices of laboratory examination of the patient (see table. 4, 5). When computed tomography (24.06) noted positive dynamics in comparison with a similar study from 13.03.93.Thus, this example demonstrates positive therapeutic effect of the drug in multiple sclerosis and no side effects.In addition, the drug significantly different (for the better) on the effect and mechanism of action of all the currently used tools. Drug treatments for multiple sclerosis, 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>the,5
FIELD: medicine, phthisiology.
SUBSTANCE: one should lymphotropically introduce the mixture of 5.0 ml 0.25%-novocaine solution and 2.0 ml 1%-dioxidine solution or the mixture of 5.0 ml 0.25%-novocaine solution and 0.5 g cefazoline subcutaneously into jugular cavity and deeply behind xiphoid process, successively 1 point once daily, 5-7 injections/course. After injection the site of injection should be treated either with heparin ointment or ultrasound (1-3 MHz, PPM 0.2 W/sq. cm, for 2 min, through Vaseline oil) followed by evaluating roentgenological dynamics of the process 10-14 d later.
EFFECT: higher efficiency of differential diagnostics.
FIELD: organic chemistry, medicine, pharmacy.
SUBSTANCE: invention describes benzamidine derivatives of the general formula (I): wherein R1 means hydrogen atom, halogen atom, (C1-C6)-alkyl or hydroxyl; R2 means hydrogen atom or halogen atom; R3 means (C1-C6)-alkyl possibly substituted with hydroxy-group, alkoxycarbonyl-(C3-C13)-alkylsulfonyl, carboxy-(C2-C7)-alkylsulfonyl; each among R4 and R5 means hydrogen atom, halogen atom, (C1-C6)-alkyl possibly substituted with halogen atom, (C1-C6)-alkoxy-group, carboxy-group, (C2-C7)-alkoxycarbonyl, carbamoyl, mono-(C2-C7)-alkylcarbamoyl, di-(C3-C13)-alkylcarbamoyl; R6 means heterocycle or similar group; each among R7 and R8 means hydrogen atom, (C1-C6)-alkyl or similar group; n = 0, 1 or 2, or their pharmacologically acceptable salts, esters or amides. Compounds elicit the excellent inhibitory activity with respect to activated factor X in blood coagulation and useful for prophylaxis or treatment of diseases associated with blood coagulation.
EFFECT: improved method for prophylaxis and treatment, valuable medicinal properties of compound.
26 cl, 2 tbl, 253 ex
FIELD: organic chemistry, medicine, pharmacy.
SUBSTANCE: invention describes diazepane derivative of the general formula (I)
or its pharmaceutically acceptable salt wherein ring B means phenyl; ring A means pyridyl substituted with halogen atom optionally, or phenyl substituted optionally with lower alkyl, lower alkoxy-group or halogen atom; X1 represents -C(=O)-NR2- or -NR2-C(=O)- wherein R2 means hydrogen atom; X2 represents -C(=O)-NR3- or NR3-C(=O)- wherein R3 means hydrogen atom; R represents hydrogen atom or halogen atom; R1 means lower alkyl. Also, invention relates to a pharmaceutical composition and inhibitor of blood coagulation activated factor X that can be used for prophylaxis and treatment of patients suffering with thrombosis or embolism.
EFFECT: valuable medicinal properties of compound.
5 cl, 5 tbl, 6 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: organic chemistry, cardiology, pharmacy.
SUBSTANCE: invention describes compounds of the formula (I)
wherein R1, R2, R3 and Ra-Rh have values given in the description. Proposed compounds are useful in prophylaxis and treatment of arrhythmia, in particular, atrial and ventricular arrhythmia, Also, the invention relates to methods for preparing compounds of the formula (I) and intermediate compounds.
EFFECT: valuable medicinal properties of compounds.
41 cl, 1 tbl, 8 ex
SUBSTANCE: the present innovation deals with preventing hemodynamic complications at restoring circulation in a prolongly ischemized limb, or due to premeditated tourniquet application during operative interference. For this purpose, 5-12 min before the onset of circulatory restoration it is necessary to start intravenous injection of antihistamine and glucocorticosteroid preparations, followed by drop-by-drop infusion of inhibitors of proteolytic enzymes which should be continued after tourniquet removal, as well. The method provides tourniquet shock and tourniquet shock-associated complications along with developing the chance for increasing the duration period of operation.
EFFECT: higher efficiency of prophylaxis.
FIELD: organic chemistry, chemical technology, medicine, pharmacy.
SUBSTANCE: invention describes bicyclic N-acylated imidazo-3-amines or imidazo-5-amines salts of the general formula (I): wherein R1 means tert.-butyl, 1,1,3,3-tetramethylbutyl, (C4-C8)-cycloalkyl, phenyl disubstituted with (C1-C4)-alkyl, -CH2Ra wherein Ra means the group -CO(OR') wherein R' means (C1-C8)-alkyl; R2 means hydrogen atom, the group -CORb wherein Rb means (C1-C8)-alkyl or (C3-C8)-cycloalkyl; R3 means (C1-C8)-alkyl, (C3-C8)-cycloalkyl, phenyl, pyridyl, furfuryl or thiophenyl; A means tri-linked fragment of ring of the formula: wherein R6 and R7 mean hydrogen atom or tetra-linked fragment of ring of the following formulae: wherein R4' means hydrogen atom or benzyloxy-group; R5' means hydrogen atom; R6' means hydrogen atom, (C1-C8)-alkyl or nitro- (NO2)-group; R7' means hydrogen atom, (C1-C8)-alkyl, or R6' and R7' mean in common the following fragment of ring: -CRi=CRj-CH=CH- wherein Ri and Rj mean hydrogen atom; R5'' means hydrogen, chlorine atom or (C1-C8)-alkyl; R6'' means hydrogen atom; R7''n means hydrogen atom, amino- (NH2)-group or (C1-C8)-alkyl; R4''', R6''' and R7''' mean hydrogen atom; R8 means (C1-C8)-alkyl or (C3-C8)-cycloalkyl; X means anion of inorganic or organic acid, or their acid-additive compounds. Also, invention relates to a method for their preparing and a pharmaceutical composition based on thereof. These new compounds show affinity to opiate μ-receptor and can be used, in particular, as analgesic agents.
EFFECT: improved preparing method, valuable medicinal properties of compounds and pharmaceutical compositions.
12 cl, 2 dwg, 32 ex
FIELD: organic chemistry, biochemistry, pharmacy.
SUBSTANCE: invention relates to new derivatives of β-carboline of the general formula (I)
showing properties of phosphodiesterase V inhibitor (PDE V). In the general formula (I) R1 means hydrogen atom; n = 0; X is taken among the group consisting of oxygen (O), sulfur (S) atoms and NRD; R2 is taken among the following group: phenyl (that can be optionally substituted with 1-3 RB), 6-membered nitrogen-containing heteroaryl and 5-6-membered heterocycloalkyl comprising 1-2 oxygen atoms and condensed with benzene ring (optionally substituted with 1-3 RB); R4 is taken among the group consisting of hydrogen atom, carboxy-group. (C1-C6)-alkylcarbonyl, di-[C1-C8)-alkyl]-aminoalkoxycarbonyl, di-[(C1-C8)-alkyl]-amino-(C1-C8)-alkylaminocarbonyl; a = a whole number from 0 to 1; Y is taken among the group consisting of -CH2, -C(O); Z is taken among the group consisting of -CH2, -CHOH, and -C(O) under condition that when Z represents -CHOH or -C(O) then X represents -NH; is taken among the group consisting of naphthyl, 5-6-membered heteroaryl comprising 1-3 heteroatoms taken among nitrogen, oxygen and/or sulfur atoms possibly condensed with benzene ring; m = a whole number from 0 to 2; R3 is taken independently among the group consisting of halogen atom, nitro-group, (C1-C8)-alkyl, (C1-C8)-alkoxy-group, trifluorophenyl, phenyl (optionally substituted with 1-3 RB), phenylsulfonyl, naphthyl, (C1-C8)-aralkyl, 5-6-membered heteroaryl comprising 1-3 nitrogen atoms in the ring (optionally substituted with 1-3 RB). Also, invention relates to a pharmaceutical composition, a method for its preparing and methods for inhibition of phosphodiesterase V activity (PDE V), and for increase of the cGMP concentration.
EFFECT: improved preparing method, valuable medicinal and biochemical properties of compounds and composition.
14 cl, 11 sch, 7 tbl, 13 ex
FIELD: organic chemistry, pharmacy.
SUBSTANCE: invention relates to new pharmaceutical compositions comprising bicyclic compound of the formula (I): wherein A means -COOH or their functional derivative; X1 and X2 mean hydrogen or halogen atom; V1 and V2 mean carbon atoms; W1 and W2 mean groups and wherein R4 and R mean hydrogen atom, hydroxy-group; Z means carbon, oxygen, sulfur or nitrogen atom; R1 means saturated or unsaturated bivalent (C1-C10)-aliphatic hydrocarbon residue; R2 means saturated or unsaturated (C1-C10)-aliphatic hydrocarbon residue; R3 means hydrogen atom and glyceride. Also, invention relates to a method for stabilizing compositions and novel bicyclic compounds. Invention provides enhancing stability of pharmaceutical composition based on its dissolving in glyceride.
EFFECT: improved and valuable properties of compositions, improved stabilization of compositions.
42 cl, 8 tbl, 8 ex
FIELD: medicine, neurology, virology.
SUBSTANCE: invention relates to treatment of neurological diseases caused by herpes virus, such as Bell's paralysis, Hunt's disease, herpetic encephalitis accompanying with damage of cerebral nerves. Invention involves using 1,4-dihydropyridine blockers of calcium channels, such as felodipine, nifedipine, nimodipine, nisodipine being taken preferably in combination with herpes virus antagonist. Invention provides repairing damaged cerebral nerves by topical expanding arteriols and recovery of local microcirculation based on specific competitive interaction of definite groups of calcium blockers of 1,4-dihydropyridine type with vasoconstrictor endothelin.
EFFECT: enhanced effectiveness of treatment.
47 cl, 2 dwg, 1 ex
FIELD: medicine, gastroenterology.
SUBSTANCE: invention relates to methods for treatment of chronic helicobacter pylori-associated gastritis. Method is carried out by monotherapy with the probiotic "Laminolakt" in the dose 3 dragees per 24 h for 1 month. Method provides elimination of Helicobacter pylori cells on the background of activation of the immune response in stomach mucosa by effect on microflora and the colon intestine immune system.
EFFECT: enhanced effectiveness of treatment.
2 tbl, 1 ex