New composition for treating metabolic syndrome

FIELD: medicine, pharmaceutics.

SUBSTANCE: present group of inventions refers to medicine, namely therapy and endocrinology, and concerns treating metabolic syndrome and diabetes. That is ensured by administering an effective amount of a composition comprising an activator of adenosine-5'-monophosphate-activated protein kinase (AMPK), and an anti-inflammatory agent having serotonergic activity.

EFFECT: administering the given composition provides the effective treatment of metabolic syndrome and diabetes by improving lipid metabolism due to inducing the enhanced oxidation of fatty acids by the ingredients of the composition.

29 cl, 4 ex

 

CROSS-REFERENCE TO RELATED APPLICATIONS

For this application priority is claimed in accordance with the provisional application U.S. 60/885212, filed January 16, 2007, the contents of which are incorporated in this description by reference.

The LEVEL of TECHNOLOGY

Metabolic syndrome is a group of metabolic risk factors including abdominal obesity, atherogenic dyslipidemia (for example, high levels of triglycerides, low levels of cholesterol in high density lipoprotein (HDL, HDL) and high levels of cholesterol low-density lipoprotein (LDL, LDL), hypertension, insulin resistance, prothrombotic state (for example, high levels of inhibitor-1 activator, fibrinogen or plasminogen), and proinflammatory state (e.g., elevated levels of C-reactive protein). Metabolic syndrome is becoming more common in the United States. It is estimated that over 50 million Americans have this disorder. Thus, there is a need to develop new drugs for effective treatment of this disorder.

The INVENTION

This invention is based on the unexpected discovery that the combination of certain known drugs found synergistic effects in the treatment of metabolic syndrome and different is cnyh other diseases.

In one aspect, the invention relates to a composition that includes a first agent can be an inhibitor of oxidative phosphorylation, ionophor, or activator, activated adenosine-5'-monophosphate protein kinase (AMPK), a second agent that possesses anti-inflammatory activity, and a third agent that possesses serotonin activity or supports it. The term "inhibitor of oxidative phosphorylation" refers to any suitable agents that inhibit oxidative phosphorylation, such as uncouplers of oxidative phosphorylation. Ionophor is lipitorhistory molecule capable of ion transfer across the lipid bilayer of cell membranes; and the AMPK activator is an agent that activates AMPK in the direction of the phosphorylation of its substrates, for example, acetyl-CoA carboxylase and malonyl-CoA decarboxylase. Examples of the first agent include Metformin (for example, chloride Metformin), phenformin, buformin, ephedrine, thyroxine, salicylanilide and salicylic acid. The second agent can be any suitable anti-inflammatory compounds (e.g., nonsteroidal anti-inflammatory compounds). Examples include aspirin, diclofenac (e.g., diclofenac potassium or diclofenac sodium, ibuprofen (e.g. the measures dexibuprofen or dexibuprofen), indomethacin, acetaminophen, nimesulide and COX-2 inhibitors (for example, the COX-2 inhibitor on the basis of nitric oxide). The third agent may be a compound which has or supports at least one of the activities of serotonin and, if used in combination with the first and second agents that effectively cures one or more target diseases according to this invention. Examples include serotonin (e.g., sulfate serotonin, complex serotonin-createsurface, or hydrochloride serotonin) and inhibitor of serotonin reuptake. The preferred composition contains hydrochloride Metformin, aspirin and complex serotonin-createsurface. Three agents mentioned above can heal target disease on the biological mechanisms that differ from those described here. For example, Metformin can heal the target disease (such as diabetes) by a different mechanism other than inhibition of oxidative phosphorylation or activation of AMPK.

In another aspect, the invention includes a composition consisting essentially of a first agent can be an inhibitor of oxidative phosphorylation, ionophor or activator of AMPK, the second agent that possesses anti-inflammatory activity, and a third agent that possesses ser is connoway activity. Used here, the term "consisting essentially of" limits the composition of three specific agents and those that essentially do not affect its basic and new features, that is described here is effective in treating the target disease. An example of such a composition contains the above-mentioned three agent and a pharmaceutically acceptable carrier.

The compositions described above may contain 5-5000 mg (for example, 5-3000 mg, 5-1500 mg or 5-1000 mg) of the first agent, 1-5000 mg (for example, 1-3000 mg, 1-1000 mg, 1-500 mg, or 1-100 mg) of the second agent, and 0.1-1000 mg (for example, 0.1 to 100 mg, 0.1 to 50 mg, or 0.1-30 mg) of the third agent, or in quantities of the same ratio as the ratio, calculated on the basis of these quantities.

In the following aspect, the invention includes a method of treating metabolic syndrome, Parkinson's disease or polycystic ovary syndrome. The method includes the administration to an individual having such a need, an effective amount of one or more of the above-described compositions. Diseases mentioned above, also include associated disorders. For example, disorders associated with metabolic syndrome include atherosclerosis, heart failure, stroke, obesity, diabetes, atherogenic dyslipidemia (for example, high levels of triglycerides, low levels of lipoprotein cholesterol you the Oka-density (HDL) and high levels of cholesterol low-density lipoprotein (LDL), hypertension, insulin resistance, prothrombinase state (for example, high levels of inhibitor-1 activator, fibrinogen or plasminogen), and proinflammatory state (e.g., elevated levels of C-reactive protein).

Applied here, the term "treatment" or "treating" refers to the introduction of one or more of the above compositions to the individual, which has the above-described disease, a symptom of such a disease or susceptibility to such a disease, with the goal of providing a therapeutic effect, for example, cure, relieve, alter, influence, improvement or prevention of a disease, symptom, disease, or predisposition to disease.

The above composition may be in dry form (e.g., powder or tablet) or in aqueous form (for example, drink or syrup). It can be a Supplement to the diet or pharmaceutical composition containing a pharmaceutically acceptable carrier). The composition can also be a drink or food. Examples include tea (for example, tea in the form of a drink, and the contents of the tea bag), soft drinks, juice (for example, the extract of the fruit and drinking the juice), milk, coffee, muffins, Breakfast cereals, chocolate and chocolate bars with filling.

First, second and third agents, you described the e, include active compounds, and their salts, prodrugs and solvate, if they apply. Salt, for example, may be formed anion and a positively charged group (e.g., amino group) in the connection. Suitable anions include chloride, bromide, iodide, sulfate, nitrate, phosphate, citrate, methanesulfonate, triptorelin, acetate, chlorophenoxyacetate, malate, tosylate, tartrate, fumarate, glutamate, glucuronate, lactate, glutarate, benzoate, embonate, glycolate, pamoate, aspartate, parachlorphenilalanine, formate, succinate, cyclohexanecarboxylate, hexanoate, octanoate, decanoate, hexadecanoate, octadecanoate, bansilalpet, trimethoxybenzoate, paratoluenesulfonyl, adamantanecarboxylic, glycoxylate, pyrrolidonecarboxylic, naphthalenesulfonate, 1-glucosephosphate, sulfite, ditional and maleate. Likewise, a salt can also be formed by a cation and a negatively charged group (e.g., carboxylate group) in the connection. Suitable cations include sodium ion, potassium ion, magnesium ion, calcium ion, and ammonium cation, such as ion Tetramethylammonium. Agents also include salts containing Quaternary nitrogen atoms. Examples of prodrugs include esters and other pharmaceutically acceptable derivatives, which, when administered to an individual, capable of providing an active connection. the Ermin "MES" refers to the complex, formed between the active compound and a pharmaceutically acceptable solvent. Examples of pharmaceutically acceptable solvents include water, ethanol, isopropanol, ethyl acetate, acetic acid and ethanolamine.

Also within the scope of this invention are one or more of the compositions described above for use in the treatment of the above diseases, and the use of such compositions in the manufacture of a medicine for the above treatment.

The details of one or more embodiments of the invention described in the detailed description below. Other characteristics, objectives and advantages of the invention will be apparent from the description and from the claims.

A DETAILED DESCRIPTION of the PREFERRED embodiments

The composition according to this invention may include three agents.

The first agent can represent, in addition to those described above, 4,6-dinitro-o-cresol, uncoupling proteins (e.g., UCP1, UCP2 or UCP3), carbonylcyanide pair(triptoreline)phenylhydrazone, carbonylcyanide meta-chlorophenylhydrazone, products C5 gene, dinitrophenol (for example, 2,4-dinitrophenol), eproperty (A23871), guanethidine, chlorpromazine, amytal, secobarbital, rotenon, progesterone, antimycin a, naphthoquinone, 8-hydroxyquinoline, carbon monoxide, cyanides, azides (e.g., NaN3 ), dikumarina, bilirubin, a bile pigment, ephedrine, hydrogen sulfide, tetraiodothyronine, quercetin, 2,4-bis(p-chloroanilino)pyrimidine, dehydrogenase glyceraldehyde-3-phosphate, oligomycin, the presence of TBT chloride, europarty, rutamycin, Venturelli, mercury compounds, dicyclohexylcarbodiimide, Dio-9, metaxalone meta-chlorophenylhydrazone, ionomycin, calcium ionophores (e.g., A23187, NMDA, CA 1001 or annealin B), compounds that increase the concentration of Ca+2in mitochondria (for example, attractionid, bangkruay acid, thapsigargin, amino acid neurotransmitters, glutamate, N-methyl-D-aspartic acid, carbachol, ionophores, inductors potassium depolarization), apoptogenic (i.e., compounds that promotirovat apoptosis), valinomycin, gramicidin, nonactin, nigericin, lasalocid and monensin. The first agent can be an activator of AMPK (for example, Metformin or phenformin, buformin, AICAR, thienopyridine, resveratrol, nootkatone, thiazole or adiponectin).

The second agent may be a steroid anti-inflammatory drugs and non-steroidal anti-inflammatory drugs. Examples of steroidal anti-inflammatory drugs include glucocorticoids, hydrocortisone, cortisone, beclomethasone, dipropionate, betamethasone, dexamethasone, prednisone, methylprednisolone, triamcinolone, acetonide fluotsinolon is, fludrocortisone and beclomethasone propionate. Examples of non-steroidal anti-inflammatory drugs (NSAIDs) include A183827, ABT963, aceclofenac, acemetacin, acetylsalicylic acid, AHR10037, alclofenac, alminoprofen, ampiroxicam, amtolmetin guacil, Amazon, methyl ether of flipron, AU8001, benoxaprofen, flufenamic benzydamine, bioprotein, baseperiod, BF388, BF389, BIRL790, BMS347070, bromfenac, bulokovu acid, butibufen, BW755C, C53, C73, C85, carprofen, CBS1108, celecoxib, CHF2003, chlorobiphenyl, trisalicylate choline-magnesium, CHX108, cimicoxib, tenoxicam, clidanac, CLX1205, COX-2 inhibitors, CP331, CS502, CS706, D1367, darbufelone, deracoxib, dexketoprofen, DFP, DFU, diflunisal, DP155, DRF4367, E5110, E6087, eltenac, ER34122, esflurbiprofen, etoricoxib, F025, etelvina, fenbufen, fenclofenac, enclosure acid, enclosin, fenoprofen, fentiazac, feprazone, frenadol, fabutan, florigene, flosulide, methanesulfonate flunixin, flufenamic acid, fluprofen, flurbiprofen, FPL62064, FR122047, FR123826, FR140423, FR188582, FS205397, furofenac, GR253035, GW406381, HAI105, HAI106, HCT2035, HCT6015, HGP12, HN3392, HP977, HX0835, HYAL AT2101, ibufenac, ibuproxam-beta-cyclodextrin, codelines, IDEA070, iguratimod, irreconcil, indoprofen, IP751, isoxepac, isoxicam, KC764, Ketoprofen, L652343, L745337, L748731, L752860, L761066, L768277, L776967, L783003, L784520, L791456, L804600, L818571, LAS33815, LAS34475, licofelone, LM 4108, lbuprofen, lornoxicam, lumiracoxib, ubuprofen, meclofenamic acid, maclife the Amat sodium, mefenamico acid, meloxicam, mercaptoethylamine, mesoporphyrin, methoxybutanol, miroprofen, mofebutazone, movetalk, MX1094, nabumetone, naproxen sodium, naproxen sodium/metoclopramide, NCX1101, NCX284, NCX285, NCX4016, NCX4215, NCX530, niflumova acid, NSAIDs based on nitric oxide (NitroMed, Lexington, MA), nitrofen, nitroprussiate, nitrosoproline, NS398, oil of Basil noble, ONO3144, herpanacine, oxaprozin, oxidant, exping, oxycodone/ibuprofen, oxyphenbutazone, P10294, P54, P8892, amicore, parcetamol, parecoxib, PD138387, PD145246, PD164387, pluripotent, pemetaan, phenylbutazone, pyrazole, piroxicam, piroxicam beta-cyclodextrin, piroxicam, pivalate, pirprofen, pranoprofen, resveratrol, R-Ketoprofen, R-Ketorolac, rofecoksib, RP66364, RU43526, RU54808, RWJ63556, S19812, S2474, S33516, salicylsalicylic acid, satyres, SC236, SC57666, SC58125, SC58451, SFPP, SKF105809, SKF86002, sodium salicylate, sudoxicam, sulfasalazin, sulindac, suprofen, SVT2016, T3788, TA60, tolmetin, talniflumate, tsopelas, tebufelone, tenidap, tenoxicam, tepoxalin, tiaprofenic acid, tilmicosin, timeproven of Arbatel, tinoridine, tiopinac, tioxaprofen, tolfenamic acid, tolmetin, triflusal, tropein, TY10222, TY10246, TY10474, UR8962, orthologue acid, valdecoxib, WAY120739, WY28342, WY41770, xenoprof, YS134, zaltoprofen, zidometacin, zomepirac.

The third agent includes serotonin and its functional equivalents. Funk is optional equivalents include serotonin transport inhibitors serotonin (for example, paroxetine, fluoxetine, fenfluramine, fluvoxamine, sertraline, imipramine, and those that were first described in WO 03/00663), modulators of the serotonin receptor 2c (for example, BVT933, DPCA37215, IK264, PNU22394, WAY161503, R-1065, YM348, and those that were first described in U.S. patent No. 3914250, WO 01/66548, WO 02/10169, WO 02/36596, WO 02/40456 and WO 02/40457, WO 02/44152, WO 02/48124, WO 02/51844, and WO 03/033479), inhibitors of serotonin reuptake (e.g., arylpyrimidine connection phenylpiperazine connection benzylpiperidine connection piperidine compounds, tricyclic gamma karbolinovye DULOXETINE connection pyrazinecarboxamide connection peridontology connection piperidinol connection, milnacipran, citalopram, sertralineliy metabolite of desmethylsertraline, noruoxetine, citalopramsee metabolite of demethylcitalopram, ESCITALOPRAM, d,l-fenfluramine, femoxetine, ifoxetine, cyanidation, litoxetine, priligy generic, nefazodone, cericlamine, trazodone, mirtazapine, fluoxetine, fluvoxamine, indalpine, indeloxazine, milnacipran, paroxetine, sertraline, sibutramine, zimeldine, trazodone hydrochloride, dexfenfluramin and those described in U.S. patent No. 6365633, WO 01/27060 and WO 01/162341), reuptake inhibitors of serotonin and noradrenaline (e.g., venlafaxine, venlafaxine metabolite O-desmethylvenlafaxine, clomipramine and clomipramine metabolite desmethylclomipramine), Academy of Sciences of the agonists serotonin 1A receptor (for example, arylpiperazine connection azaheterocycle derivatives of heterocycle-condensed benzodioxane, or buspirone), antagonists of serotonin 2A receptor (for example, MDL100907 and fananserin), antagonists of the serotonin 2B or 2C-receptor (e.g., pyrazino(Aza)indole compounds or serotoninergicheskie connection), antagonists of serotonin 6 receptor (for example, 5-halogen-simplest linkages of tryptamine compounds), antagonists of serotonin 7 receptor (for example, 5-halogen-simplest linkages of tryptamine compounds or quinoline compounds), antagonists of serotonin and dopamine (e.g., olanzapine and ziprasidone), inhibitors of reuptake of monoamines (for example, amides), inhibitors of pyridazine-aldoses reductase (for example, pyridazinone connection), serotoninergicheskie agents, stimulant of serotonin receptors (e.g., mesilate of ergoloid or mesilate of pergolid), a stimulant of serotonin synthesis (for example, vitamin Bl, vitamin B3, vitamin B6, Biotin, S-adenosylmethionine, folic acid, ascorbic acid, magnesium, coenzyme Q10 or piracetam), or serotonin agonists (e.g., fenfluramine).

All connections mentioned above are known medications and easily accessible. Some of them can be purchased from chemical companies such as Sigma-Aldrich, St. Louis, MO. Modes of introduction of these pharmaceutical preparations the Arat well-known and if you want, can be easily re-installed. Effective doses will vary, as established by experts in this field, depending on the type or extent of a disease that can be cured; size, weight, age and sex of the individual; route of administration; the applied filler; possible joint use of another therapeutic treatment. Daily dose of the above-described compositions can range 5-5000 mg (for example, 10-2500 or 10-3000 mg) of the first agent, 1-5000 mg (for example, 2-1000 or 2-3000 mg) of the second agent, and 0.1-1000 mg (e.g., 1-50 mg) of the third agent.

One aspect of this invention relates to a method of introducing an effective amount of one or more of the above compositions to the individual to treat the above diseases. Such an individual may be identified by health workers on the basis of the results of any suitable diagnostic method. The term "effective amount" refers to the amount of one or more of the compositions described above, which is required to achieve a therapeutic effect in treatment of the individual.

For the practical implementation of the method according to the present invention, one or more of the above compositions can be introduced parenteral, oral, nasal, rectal, topical, or transbuccal. Used here, the term "parenteral" refers to the technique of subcutaneous, percutaneous, intravenous, intramuscular, intraarticular, intraarterial, intrasynovial, in the epigastric fossa, intrathecal, intracranial wound or injection, as well as any suitable infusion.

Sterile injectable composition can be a solution or suspension in a nontoxic acceptable for injecting the diluent or solvent such as a solution in 1,3-butanediol. Acceptable carriers and solvents that can be used are mannitol, water, ringer's solution and isotonic sodium chloride solution. In addition, non-volatile oils are typically used as a solvent or suspendida environment (for example, synthetic mono - or diglycerides). Fatty acid such as oleic acid and its glyceride derivatives, can be applied to obtain an injectable drug, as well as natural pharmaceutically-acceptable oils, such as olive oil or castor oil, especially in their polymethoxyflavones options. These oil solutions or suspensions may also contain long-chain alcohol diluent or dispersing agent, carboxymethyl cellulose or similar dispersing agents. Other commonly used surface-Akti the substances, such as twins (Tweens®or spiny (Spans®), or other similar emulsifiers agents or enhance the bioavailability of the agents that are usually used in the manufacture of pharmaceutically acceptable solid, liquid, or other dosage forms can also be used for purposes retseptoriani.

Composition for oral administration can be any orally acceptable dosage form including capsules, tablets, emulsions and aqueous suspensions, dispersions and solutions. In the case of tablets commonly used carriers include lactose and corn starch. Also typically added lubricant such as magnesium stearate. For oral administration in capsule form diluents which can be used include lactose and dried corn starch. If water suspension or emulsion is introduced orally, the active ingredient may be suspended or dissolved in the oil phase, or United with emulsification, or suspendresume agents. If desirable, may be added certain sweetening, flavoring or coloring agents.

Nasal spray or composition for inhalation can be prepared according to techniques well known in the art of pharmaceutical formulations. For example, such a composition can be obtained in the form of a solution in physiological solution, using benzyl alcohol or other suitable preservatives, absorption promoters to enhance bioavailability, fluorocarbons, and/or other increase the solubility or dispersing agents known in the art.

Composition for local injection can be prepared in the form of an ointment, gel, plaster, emulsion, lotion, foam, cream with sexandfunny or amphiphilic emulsion system (mixed phase oil-in-water, water-in-oil), liposomal form, transpersonal form, in the form of a paste or powder.

Any of the compositions described above can also be entered in the form of suppositories for rectal administration. They can also be made so that the composition is released in the intestinal tract. For example, the composition is placed in a solid segment or compartment of the capsule, which has respectively a matrix or a wall, or partition containing enteric polymer which is dissolved or dispersed at a pH of thin or large intestine to release the medicinal compounds in the gut. Such suitable polymers have been described above, for example, with reference to U.S. patent No. 5705189.

The carrier in the pharmaceutical composition must be "acceptable" in the sense that it must be compatible with the active ingredient of the composition (and preferably, capable of stabilizing the act is wny component) and not be harmful under treatment to the individual. One or more increase the solubility of agents can be used as pharmaceutical excipients for delivery of active thiophene compounds. Examples of other carriers include colloidal silicon dioxide, magnesium stearate, cellulose, sodium lauryl sulphate, and the product is Yellow D&C #10.

The compositions described above can be preliminarily investigated for their efficacy in treating above-described diseases in the study in vitro and then confirmed in experiments on animals (see Examples 1-4 below) and clinical trials. Other methods will be obvious to specialists in this field.

The specific examples given below should be interpreted only as illustrative and not limiting in any way the scope of invention. It is assumed that without any additional modification, the person skilled in the art can, based on the above description, to apply the present invention in its entirety. All publications cited here, are included in this description by reference in their entirety.

Example 1: in vivo Studies of the effectiveness against obesity.

Each of the 120 of eight female rats, Sprague-Dawly, SD and 100 eight-week SD male rats were given an unlimited amount of feed for 14 days. The amount of food eaten and change masakado rats was measured daily. Then calculate the rate of food digestion for each rat using the following equation:

R=100×ΔW/F1%

In this equation, R represents the rate of food digestion, ΔW is the change in mass, F1represents the daily amount of food eaten. Then took 88 females and 77 males rats and divided in 11 groups, where each group consisted of 8 female rats and 7 male rats. Each of the following 10 test compositions was dissolved in 10% aqueous glucose solution was administered subcutaneously to a group of rats for 28 days daily: (1) 15 mg/kg chloride Metformin (hereinafter referred to as Metformin), (2) 0.25 mg/kg of the complex serotonin and creationinterface (hereinafter referred to as serotonin), (3) 4 mg/kg of aspirin, (4) 0.25 mg/kg serotonin + 4 mg/kg aspirin (5) 15 mg/kg Metformin + 4 mg/kg aspirin (6) 15 mg/kg Metformin + 0.25 mg/kg of serotonin, (7) 5 mg/kg Metformin + 4 mg/kg aspirin + 0.25 mg/kg of serotonin, (8) 15 mg/kg Metformin + 4 mg/kg aspirin + 0.25 mg/kg of serotonin, (9) 45 mg/kg Metformin + 4 mg/kg aspirin + 0.25 mg/kg of serotonin, and (10), 2 mg/kg sibutramine. Rats in the 11th group did not receive any medication and was used as a control group. The results showed that rats treated with the combination of Metformin, aspirin and less serotonin, increasing their weight than rats receiving each of the th component separately or any combination of the two components. Further, the average weight gain of rats decreased with increasing daily dose of Metformin.

The total number of the received feed for 28 days were measured for all groups. The result shows that the total number of accepted food groups (1)to(10) were essentially the same as the control group (11). In other words, the test composition was not significantly influenced by the appetite of rats.

Indicators of food digestion was calculated for all groups. The results showed that rats treated with the combination of Metformin, aspirin and serotonin, may have a much lower rate of food digestion than rats treated with each component separately or any combination of the two components.

Example 2: Issledovaniia antihypertensive effects in vivo.

60 male rats Sprague-Dawly (90-110 g) were given medical laboratory animal center Guang Dong (FuoShan, Guang Dong, China). After anestesiologia each rat U-shaped silver clip with an internal diameter of 0.2-0.25 mm was used for narrowing of the renal artery. Two weeks after surgery were selected 40 rats with good recovery and were divided into 5 groups, where each group consisted of 8 rats. Each of the following 4 test compositions was dissolved in 10% aqueous glucose solution was administered to rats daily for 9 weeks: (1) 45 mg/kg metfor the ina + 4 mg/kg aspirin + 0.25 mg/kg of serotonin, (2) 15 mg/kg Metformin + 4 mg/kg aspirin + 0.25 mg/kg of serotonin, (3) 5 mg/kg Metformin + 4 mg/kg aspirin + 0.25 mg/kg of serotonin and (4) 2 mg/kg nifedipine. Rats in the 5th group was injected only 10% aqueous glucose solution, and they were used as a control group. The test composition was injected subcutaneously, except nifedipine, which was administered by gastric perfusion. Tail blood pressure of each rat was measured at the end of 5 weeks and 9 weeks.

The results show that the blood pressure of rats in group (1) at the end of the 5th and 9th weeks were significantly lower than the pressure in rats in the control group (i.e., group (5)) and the group, in which rats received nifedipine (i.e., group (4)).

Example 3: in vivo Studies on acute antihypertensive effects.

Renovaskulyarnoy hypertensive rats were received as follows: male rats Sprague-Dawly (90-110 g) was anestesiologi pentobarbital sodium (45 mg/kg). U-shaped silver clip with an internal diameter of 0.2-0.25 mm was used for narrowing of the renal artery. Blood pressure of rats was significantly increased after 3-6 weeks and stabilized after approximately 8 weeks. Rats, who had a systolic pressure in the range of 180-240 mm Hg used in the following stages.

Rats prepared as described above were divided into 4 groups. Each of the following 3-in-law who has been created compositions was dissolved in 10% aqueous glucose solution: (1) 45 mg/kg Metformin + 4 mg/kg aspirin + 0.25 mg/kg of serotonin, (2) 15 mg/kg Metformin + 4 mg/kg aspirin + 0.25 mg/kg of serotonin and (3) 5 mg/kg Metformin + 4 mg/kg aspirin + 0.25 mg/kg of serotonin. Rats in the 4th group was injected only 10% glucose solution, and they were used as a control group. Each rat was then anestesiologi pentobarbital sodium (45 mg/kg) and were attached to the stand. In the trachea tube was inserted to maintain breathing rats. Then another tube was inserted into the neck artery for measuring blood pressure. Blood pressure was measured using a system of collecting and processing biological signal BL-420E. When blood pressure in neck artery of the rat stabilized, introduced a test composition subcutaneously or 10% aqueous solution of glucose into the abdominal cavity. Blood pressure cervical artery was measured through 15, 30, 45, 60, 90, 120, 150, 180, 210 and 240 minutes after injection.

The results showed that blood pressure in neck artery of rats in groups (1) and (2) begins to decrease after 15 minutes and reaches the lowest levels through 120-150 minutes. Average blood pressure in neck artery reduced the maximum 29.7±5.2 mm Hg and 20.3±2.9 mm Hg, respectively, compared with the pressure measured prior to the introduction of the test composition. Blood pressure in neck artery of rats did not return to the level before the introduction of the test composition even after 4 hours. The results also coated the zali, that the test composition does not influence significantly on the heart rate of rats.

Example 4: analysis of the effects of reducing glucose levels in the blood in vivo.

The male rats Sprague-Dawly (SD) (180-210 g) was intraperitoneally injected with streptozocin (50 mg/kg) to induce type 2 diabetes. Rats with glucose levels in the blood is higher than 17 mmol/l after injection, distributed randomly in five groups, each group consisted of 10 rats. Rats in each of the five groups then worked three test compositions described in Example 3 above, that is, 45 mg/kg Metformin + 4 mg/kg aspirin + 0.2 mg/kg of serotonin (high dose), 15 mg/kg Metformin + 4 mg/kg aspirin + 0.2 mg/kg of serotonin (medium dose) and 5 mg/kg Metformin + 4 mg/kg aspirin + 0.2 mg/kg of serotonin (low dose); Metformin separately at the dosage is 0.135 g/kg (Metformin); and a control the group with medium (control). 10 normal male rats Sprague-Dawly used as the control group, were subjected to the same treatment.

The level of glucose in the blood of each of the treated rats was measured before treatment and after 3 hours, 6 hours, 3 days, 7 days, 14 days and 21 days after treatment. The results thus demonstrate that the three test compositions significantly reduce the levels of glucose in the blood of rats with diabetes of the 2nd type.

OTHER embodiments of the

All signs, first disclosed in this description may be combined in any combination. Every sign, first described in this document can be replaced by an alternative sign, serving the same, equivalent, or similar purpose. Thus, unless otherwise approved, each first described the characteristic represents the only example of a generic series of equivalent or similar features.

From the above description, the specialist in the art can easily set the essential characteristics of this invention and, without deviating from the essence and scope, can make various changes and modifications of the invention in order to adapt the invention to various uses and conditions. Thus, other ways of implementation are also within the scope of the following claims.

1. Composition for treatment of a condition selected from the group consisting of metabolic syndrome and diabetes, containing:
the first agent representing the activator of adenosine 5'-monophosphate-activated protein kinase (AMRS);
a second agent that possesses anti-inflammatory activity; and
a third agent that possesses serotonin activity or supports it, where a third agent selected from the group consisting of:
(1) Inga is itora transport of serotonin;
(2) modulator serotonin receptor 2C;
(3) the inhibitor of the reuptake of serotonin;
(4) the inhibitor of the reuptake of serotonin and norepinephrine;
(5) an antagonist of a serotonin 1A receptor;
(6) an antagonist of serotonin and dopamine;
(7) the inhibitor of the reuptake of monoamines;
(8) an inhibitor of pyridazine-aldoses reductase;
(9) serotoninergicheskogo agent;
(10) a stimulant of serotonin receptor and
(11) agonist serotonin.

2. The composition according to claim 1, in which the first agent is selected from the group consisting of Metformin, phenformin, buformin, AICAR, thienopyridines, resveratrol, nootkatone, thiazole and adiponectin.

3. The composition according to claim 1, in which the first agent is a hydrochloride Metformin or phenformin.

4. The composition according to claim 3, in which the first agent is Metformin hydrochloride.

5. The composition according to claim 1, in which the second agent is a nonsteroidal anti-inflammatory compound.

6. The composition according to claim 1, in which the second agent is an aspirin, diclofenac, ibuprofen, indomethacin, acetaminophen, nimesulide or inhibitor SOH-2.

7. The composition according to claim 6, in which the second agent is an aspirin or celecoxib.

8. The composition according to claim 1, in which the third agent is a serotonin or inhibitor of serotonin reuptake.

9. The composition according to claim 8, in which the third agent is a sulfate of serotonin, complex serotonin-creationinterface or hydrochloride serotonin.

10. The composition according to claim 1, where the composition comprises 5-5000 mg first agent, 1-5000 mg the second agent and 0.1-1000 mg of the third agent.

11. The composition of claim 10, where the composition comprises 5-1500 mg first agent, 1-1000 mg of the second agent, and 0.1-100 mg of the third agent.

12. The composition according to claim 11, where the composition comprises 5-1000 mg first agent, 1-500 mg of the second agent, and 0.1-50 mg of the third agent.

13. The composition according to claim 1, where the composition contains hydrochloride Metformin, aspirin and complex serotonin-creationinterface.

14. The composition according to item 13, where the composition comprises 5-5000 mg of Metformin hydrochloride, 1-5000 mg aspirin and 0.1-1000 mg complex serotonin-creationinterface.

15. The composition according to 14, where the composition comprises 5-1500 mg of Metformin hydrochloride, 1-1000 mg of aspirin and 0.1-100 mg of the complex serotonin-creationinterface.

16. The composition according to item 15, where the composition comprises 5-1000 mg of Metformin hydrochloride, 1-500 mg of aspirin and 0.1-50 mg of the complex serotonin-creationinterface.

17. The composition according to claim 1, where the composition further comprises a pharmaceutically acceptable carrier.

18. The composition according to claim 1, where the composition consists essentially of the first, second and third agents.

19. The composition according to p in which activate the AMRS selected from the group consisting of Metformin, phenformin, buformin, AICAR, thienopyridines, resveratrol, nootkatone, thiazole and adiponectin.

20. The composition according to p, in which the second agent is a nonsteroidal anti-inflammatory compound.

21. The composition according to claim 20, in which the second agent is an aspirin or inhibitor SOH-2.

22. The composition according to p, in which the third agent is a sulfate of serotonin, complex serotonin-creationinterface or hydrochloride serotonin.

23. The composition according to p, where the composition contains hydrochloride Metformin, aspirin and complex serotonin-creationinterface.

24. The use of a composition according to claim 1 for obtaining a medicinal product for the treatment of metabolic syndrome.

25. The application of paragraph 24, where the composition consists essentially of the first, second and third agents.

26. The use of a composition according to claim 1 for obtaining a medicinal product for the treatment of obesity.

27. Use p, where the composition consists essentially of the first, second and third agents.

28. The use of a composition according to claim 1 for obtaining a medicinal product for the treatment of diabetes.

29. Use p, where the composition consists essentially of the first, second and third agents.



 

Same patents:

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to ophthalmology and can be used for treatment of diabetic diffuse macular edema. For this purpose 0.5 ml of 1% dexason solution and 0.5 ml of emoxipin are successively introduced in injection into parabulbar space and magnetic stimulation of optic analyser is performed. Magnetic stimulation is performed by pulse alternating magnetic field with growing strength within 6-12 mT with 50 Hz frequency and 10 min duration. Course of treatment constitutes 10 sessions.

EFFECT: method ensures efficient non-traumatic treatment of the last stage of proliferative diabetic retinopathy.

24 dwg, 4 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: described are new triazolopyrimidine derivatives of general formula (I): wherein R1 means hydrogen or alkyl; R2 means hydrogen; R3 means optionally substituted C3-8cycloalkyl, optionally substituted bridged monocyclic C6-cycloalkyl, optionally substituted phenyl, optionally substituted 6-member heterocyclyl containing one or two heteroatoms specified in O and N, etc., a pharmaceutical composition containing them, and using the compounds and composition for inhibiting the enzyme type 1 diacylglycerol-O-acyltransferase (DGAT) for treating type 2 diabetes mellitus, obesity, high plasma triglycerides, metabolic syndrome, etc.

EFFECT: there are presented new triazolopyrimidine derivatives.

11 cl, 73 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a selective thiazolidinedione analogue to be used in treating and preventing diabetes and dyslipidemia, representing 5-(4-(2-(3-methoxyphenyl)-2-oxoethoxy)benzyl)thiazolidine-2,4-dione or a pharmaceutically acceptable salt thereof. Also, the invention refers to a pharmaceutical composition for diabetes and dyslipidemia, containing an effective amount of 5-(4-(2-(3-methoxyphenyl)-2-oxoethoxy)benzyl)thiazolidine-2,4-dione or the pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. .

EFFECT: what is produced is the selective thiazolidinedione analogue decreasing binding and activating of the PPARγ nuclear transcription factor.

4 cl, 2 tbl, 10 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutical industry, namely a drug preparation for treating diabetes. A method for preparing the drug preparation for diabetes mellitus with the drug preparation containing extracts prepared of the following herbal raw materials: Radix Trichosanthis (trichosanthes root), Radix Bupleuri (thoroughwax root), Fructus Aurantii Immaturus (immature bitter orange fruit), Radix et Rhizoma Rhei (rhubarb root and rhizomes), Rhizoma Pinelliae (pinellia rhizomes), Radix Scutellariae (Baical skullcap root), Rhizoma Coptidis (coptis chinensis rhizomes), Radix Paeoniae Alba (white peony root) and Fructus Mume (wild plums) taken in certain proportions, and additionally may contain pharmaceutically acceptable adjuvants (versions). The drug preparation for diabetes mellitus.

EFFECT: drug preparation is effective for diabetes mellitus.

24 cl, 1 tbl, 36 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: there are presented: agent applicable for treating or preventing diseases involving the enzyme dipeptidyl peptidase-IV (DPP-IV) representing Limiglidol (the same 9-diethylaminoethyl-2,3-dihydroimidazo[1,2-a]benzimidazole dihydrochloride, the same diabenol), a pharmaceutical composition thereof for the same application, using Limiglidol for preparing the pharmaceutical composition for the same application and using Limiglidol for normalising blood incretins (e.g., GLP-1, GIP decomposed under action of DPP-IV). What is shown is a high selectivity of Limiglidol in relation of DPP-IV.

EFFECT: invention enables using Limiglidol for preventing, delaying progression and/or treating conditions the pathogenesis of which involves the enzyme DPP-IV, including sterility, polycystic ovary syndrome, growth disorder, asthenia, arthritis, allograft rejection, autoimmune diseases (sclerodermia and multiple sclerosis), a variety of immunomodulatory diseases (lupus erythematosus and psoriasis), AIDS, intestinal diseases (necrotic enteritis, microvilli involving diseases or abdominal diseases), intestinal inflammatory syndrome, atrophy, etc.

10 cl, 1 dwg, 2 tbl, 1 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compositions enriched with phytosterols. The method of producing porous microparticles containing phytosterols involves preparation of a homogeneous melt of a composition containing a phytosterol component and a component selected from at least one C10-C26 fatty acid, monoglyceride of a C10-C26 fatty acid and/or a metal salt and a C10-C26 fatty acid; hardening the obtained melt to form a solid amorphous substance; treating the obtained solid amorphous substance in a fine powder; mixing the obtained powder in an aqueous phase; separating the porous microparticles from the aqueous phase and drying the porous microparticles. The obtained porous microparticles are used to produce a pharmaceutical composition for reducing blood cholesterol level in mammals and for making a food product rich in phytosterols. The porous microparticles are also used in granulate form.

EFFECT: invention enables to obtain a composition of phytosterols with high bioavailability and long storage life.

25 cl, 2 dwg, 8 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a compound of formula (I) or to a salt thereof: The invention also refers to a method for preparing said compound, a pharmaceutical composition for treating the diseases caused by increased vascular contraction, proliferation or inflammation caused by endothelin on the basis of said compound.

EFFECT: what is prepared is the novel compound and the salts thereof to be used in medicine for treating hypertension, pulmonary hypertension, diabetic arteriopathy, cardiac failure, erectile dysfunction and angina pectoris.

14 cl, 4 tbl, 1 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: presented group of inventions refers to medicine. What is presented is a method for preventing and treating the diabetes mellitus complications associated with the developing degenerative processes of the nervous tissue, comprising administering a medicine containing a peptide of general formula Pro-Gly-Pro, or a pharmaceutically acceptable salt thereof in effective amounts. There are presented pharmaceutical composition comprising said peptide for the neuroprotective therapy of the complications of diabetes mellitus and the method for preparing it.

EFFECT: group of inventions enables the more effective prevention and treatment of the diabetes mellitus complications associated with the developing degenerative processes of the nervous tissue by the use of the peptide Pro-Gly-Pro, or a pharmaceutically acceptable salt thereof.

9 cl, 2 dwg, 4 tbl, 7 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel 5-halogen-substituted oxindole derivatives of formula I: , where: R1 denotes hydrogen, methoxy or ethoxy group; R2 denotes hydrogen or a methoxy group; R3 denotes hydrogen, methyl, ethyl, n-propyl or isopropyl; R4 denotes an ethoxy or isopropoxy group; R5 denotes H or methyl; R6 denotes Cl or F; X1 denotes O, NH or CH2; X2 and X3 denotes N or CH under the condition that X2 and X3 do not denote N at the same time; as well as pharmaceutically acceptable salts thereof. The invention also relates to pharmaceutical compositions for treating and/or preventing vasopressin-dependent diseases, which contain derivatives of formula I, and use thereof in treating vasopressin-dependent diseases.

EFFECT: high efficiency of using said compounds.

25 cl, 8 ex, 2 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to medicine, namely to pharmaceutical compositions for topical application containing insulin and liposomes. What is described is a pharmaceutical composition for topical application, containing insulin and liposomes in the form of a biofilm having rapid cutaneous penetration, and an ability to reduce blood glucose.

EFFECT: what is presented is the composition having rapid cutaneous penetration.

4 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: described are new triazolopyrimidine derivatives of general formula (I): wherein R1 means hydrogen or alkyl; R2 means hydrogen; R3 means optionally substituted C3-8cycloalkyl, optionally substituted bridged monocyclic C6-cycloalkyl, optionally substituted phenyl, optionally substituted 6-member heterocyclyl containing one or two heteroatoms specified in O and N, etc., a pharmaceutical composition containing them, and using the compounds and composition for inhibiting the enzyme type 1 diacylglycerol-O-acyltransferase (DGAT) for treating type 2 diabetes mellitus, obesity, high plasma triglycerides, metabolic syndrome, etc.

EFFECT: there are presented new triazolopyrimidine derivatives.

11 cl, 73 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to bupropion hydrobromide and formulations thereof, and applications thereof. The pharmaceutical composition contains an effective amount of bupropion hydrobromide, and at least one pharmaceutically acceptable adjuvant. The composition is applicable as a drug for preventing and/or decreasing a rate of convulsions and/or attacks associated with the administration of bupropion, in treating major depressive disorder, bipolar affective disorder, other affective disorders, anxiety disorder, general neurotic syndrome, panic disorder, posttraumatic stress disorder, nicotine addiction, obesity, attention deficit/hyperactivity disorder, restless legs syndrome (Ekbom syndrome), sexual dysfunctions and seasonal mood disorders.

EFFECT: invention provides reducing serious side-effects associated with the administration of bupropion.

9 cl, 54 dwg, 42 tbl, 8 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: modified release pharmaceutical composition of bupropion hydrobromide contains a core with a therapeutically effective amount of bupropion hydrobromide and a controlled release polymeric coating. The coating contains a water-insoluble polymer in an amount of 1 wt % to 12 wt % of tablet weight and a water-soluble polymer in an amount of 1.5 wt % to 10 wt % of weight tablet. The above coating surrounds the core at least partially. The composition releases bupropion hydrobromide in a dissolution medium containing 0.1N HCl and 5%-40 vol % of ethanol at a rate of approximately 1.1 or less than a release rate of bupropion hydrobromide from a modified-release similar pharmaceutical composition in a dissolution medium containing 0,1N HCl, measured over the range of time at least from 0 to 2 hours by means of type I USP apparatus at 75 rpm and at 37 ±5°C.

EFFECT: invention provides a reduction in the alcohol-caused dose fall (drop) of bupropion hydrobromide.

9 cl, 55 dwg, 46 tbl, 3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: compounds of the present invention are novel peptide analogues of oxyntomodulin (oxm) wherein one or more amino acid residue of the sequence oxm are replaced. The replacement of amino acid residues 15-24 of the peptide oxm either by amino acid residues 968-977 of the α-latroxin peptide (and versions thereof), or by amino acid residues 15-24 of extendin-4 (and versions thereof), or combining the amino acid residues of these sources, and/or the replacement of amino acid residues 27-33 of the peptide oxm by amino acid residues 27-33 of extendin-4, and/or adding the amino acid residues to an C-terminal of the peptide, enables producing a number of the analogues oxm presenting oxm-like activity to reduce food consumption, and according to some other aspects, more evident ability to reduce food consumption.

EFFECT: reduced food consumption.

32 cl, 779 dwg, 106 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutical industry, particularly to a composition for appetite suppression and body weight stimulation, as well as to a composition possessing antidepressant and antiasthenic activity. Use of the composition containing Griffonia simplicifolia extract as an L-tryptophan or 5-hydroxytryptophan source and Klamath algae extract for preparing a product for sublingual or nasal administration to suppress appetite and to stimulate weight loss in an individual. Use of the composition containing Griffonia simplicifolia extract as the L-tryptophan or 5-hydroxytryptophan source and Klamath algae extract for preparing the product for sublingual or nasal administration, possessing antidepressant and antiasthenic activity for improving attention, tone and mood in an individual. A composition for appetite suppression and weight loss stimulation. A composition for tone and mood improvement possessing natural antidepressant activity, and for attention and mental energy improvement ensured by an antiasthenic effect.

EFFECT: compositions are effective to suppress appetite, to stimulate weight loss, as well as to improve tone and mood, and to improve attention and mental energy.

12 cl

FIELD: medicine, pharmaceutics.

SUBSTANCE: there are offered: a pharmaceutical composition for preventing or treating atherosclerosis, metabolic syndrome, diabetes, obesity or their symptoms, or the combinations thereof, containing a pharmaceutically effective amount of D-tagatose or a salt, sugar alcohol, hydrate, solvate, ester or amide thereof, and a pharmaceutically effective amount of a second pharmaceutically active agent containing stilbene or a stilbenoid component or any salt, alcohol, hydrate, ester, amide, polymorph, isomer thereof, or a combination thereof, a related method of treating or preventing these diseases, the use of said composition for preparing a medicine or vaccine for the same application and a food stuff containing a pharmaceutically effective amount of D-tagatose or a salt, sugar alcohol, hydrate, solvate, ester or amide thereof, and a pharmaceutically effective amount of a second pharmaceutically active agent containing stilbene or a stilbenoid component or a salt, alcohol, hydrate, ester, amide, polymorph, isomer thereof, or a combination thereof.

EFFECT: declared combination reduces blood plasma triglyceride, including in additional carbon diet.

30 cl, 3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to tetrahydroimidazo[1,5-a]pyrazine derivatives of formula I or to their pharmaceutically acceptable salts (I), wherein: Ar represents phenyl, wherein phenyl is additionally substituted by 1-3 substitutes independently specified in halogen; R1 represents trifluoromethyl; R2 is specified in a group consisting of hydrohyl, alkyl having 1 to 4 carbon atoms, alkoxyl having having 1 to 4 carbon atoms, cycloalkyl representing a 5-6-member monocyclic ring group consisting of carbon completely, and -NR4R5, wherein each alkoxyl is optionally substituted by one group specified in a group consisting of phenyl and -OC(O)OR8; R3 is specified in a group consisting of a hydrogen atom and alkyl having 1 to 4 carbon atoms; each of R4 and R5 is independently specified is a group consisting of a hydrogen atom, alkyl having 1 to 4 carbon atoms, cycloalkyl representing a 3-8-member monocyclic ring group consisting of carbon completely, phenyl and pyridinyl, wherein each alkyl or phenyl is optionally substituted by one or more group specified in a group consisting of halogen, a cyano group, -SO2R7, -NR4R5 and -C(=O)OCH3; or R4 and R5 together with an atom, whereto attached form a 5-6-member heterocycle wherein the 5-6-member heterocycle optionally contains one or more N, O or S atom, and each 5-6-member heterocycle is optionally substituted by one or more groups consisting of halogen, hydroxyl, an amino group, alkyl having 1 to 4 carbon atoms, hydroxyalkyl 1 to 4 carbon atoms, -SO2R7, -C(O)NR4R5, -C(O)R7, =O; R7 represents alkyl 1 to 4 carbon atoms; and R8 is specified in a group consisting of alkyl 1 to 4 carbon atoms, and cycloalkyl representing a 5-6-member monocyclic ring group consisting of carbon completely. The invention also refers to methods for preparing them, a pharmaceutical composition having dipeptidyl peptidase IV inhibitory activity and containing said derivatives.

EFFECT: there are produced new compounds and composition on their basis which can find application in medicine for treating type 2 diabetes mellitus or hyperglycemia.

17 cl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of formula I , wherein R2 means methyl, Y means carbon or nitrogen, and R1, R3 and R4 have the value specified in the patent claim. Also, the invention refers to a pharmaceutical composition for the use as a pharmaceutical drug having activity of a phosphatidylinositol-3-kinase inhibitor, to the use of the compounds of formula I for preparing the pharmaceutical drug for treating a disease mediated by phosphatidylinositol 3-kinase and to a method for preparing the compounds of formula I .

EFFECT: preparing the compounds of formula I possessing activity of the phosphatidylinositol-3-kinase inhibitor.

10 cl, 5 tbl, 51 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to novel pyridyloxy derivatives or its pharmaceutically acceptable ester or a pharmaceutically acceptable salt of the mentioned derivatice or ester of general formula (I), wherein R represents a pyridyl group substituted by 1-3 groups independently specified in a group of substitutes A; the group of substitutes A represents a group comprising halogen atom, C1-C6 alkyl group and C1-C6 alkoxy group, and Me represents a methyl group. Also, the invention refers to specific compounds of formula (I), to a pharmaceutical composition and a receptor-γ activator/modulator on the basis of a compound of formula (I), to a method of treating and/or preventing a disease.

EFFECT: there are prepared novel pyridyloxy derivatives effective in treating the disease mediated by peroxisome proliferator activated receptor-γ (PPAR) γ.

37 cl, 2 tbl, 21 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a phenylpyrazol derivative presented by formula (1) or to its pharmaceutically acceptable salt: wherein R1 and R2, which may be identical or different, each represents C1-C6 alkyl, or R1 and R2 are coupled together with an adjacent nitrogen atom to form a 5-6-merous saturated heterocylic ring (wherein the mentioned saturated heterocylic ring may be substituted by halogen or C1-C6 alkyl), n represents an integer 0 to 2, T represents a hydrogen atom, halogen or C1-C6 alkyl, and R has one of formulas (I)-(V), (VII) or (VIII):

(wherein Z1 and Z2, which may be identical or different, each represents -CH2-, -O- or -NR11-, p represents an integer 0 to 3, q represents an integer 0 to 1, r and s which may be identical or different, which represents an integer 0 to 2, R3 represents halogen, C1-C6 alkyl, or hydroxy, R4 and R5 which may be identical or different, each represents a hydrogen atom, C1-C6 alkyl (wherein said C1-C6 alkyl may be substituted by hydroxy, hydroxy- C1-C6 alkoxy, C2-C7 alkoxycarbonyl or carboxy), or formula -(CH2)m-Ar1 (wherein Ar1 represents wherein (wherein said phenyl is substituted by halogen or C1-C6 alkyl), and m represents an integer 0 to 1), R6 represents oxo, R7 represents a hydrogen atom or C1-C6 alkyl, R8 represents C1-C6 alkyl (wherein said C1-C6 alkyl may be substituted by halogen), C1-C6 alkoxy (wherein said C1-C6 alkoxy is substituted by halogen) or formula -(CH2)1-Ar2 (wherein Ar2 represents phenyl (wherein said phenyl is substituted by C1-C6 alkoxy, hydroxyl or cyano) or pyridinyl, and 1 represents an integer O to 1), G represents -CO- or -SO2-, R9 represents C1-C6 alkyl, C1-C6 alkoxy, phenyl (wherein said phenyl may be substituted by halogen or pyridinyl, and R11 represents C1-C6 alkyl)}.

EFFECT: there are produced new compounds and a preventive or therapeutic agent on the basis of said compounds which can find application in medicine for treating dementia, Alzheimer's disease, attention deficit/hyperactivity disorder, schizophrenia, epilepsy, convulsions of central genesis, eating behaviour disorders, obesity, diabetes, hyperlipidemia, sleep disturbances, narcolepsy, sleeping apnoea syndrome, circadian rhythm disorder, depression or allergic rhinitis.

12 cl, 3 tbl, 72 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a powdered preparation for soft tissue regeneration with an antibacterial effect. The preparation contains 0.07-0.09 wt % of copper nanoparticles sized 30-40 nm, 0.03-0.05 wt % of zinc nanoparticles sized 30-70 nm, and low-molecular chitosan.

EFFECT: invention improves the effectiveness of wound healing, including in septic and infected ones, while simplifying the processes of preparing and using the preparation, and also prolonging a shelf life thereof.

2 cl, 3 ex

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