SUBSTANCE: invention refers to medicine, particularly pharmaceutical preparations, namely: plasters for transdermal application. Substance of invention consists in the fact that a transdermal plaster representing a matrix system and comprising a lining layer, a matrix layer and a lightproof protective coating in the following proportions is produced: 6.72 wt % of hypoxene substance, 15.11 wt % of sodium metabisulphite in propylene glycol with 0.067% of sodium metabisulphite, as well as 56.0 wt % of 95% ethanol and 22.17 wt % of PVP K30. The plaster aims at the transdermal introduction of hypoxene. A plaster area is 25 cm2.
EFFECT: offered plaster used for treating and preventing chronic diseases allows avoiding the problems related to oral administration, improves patient compliance, enables prolonged maintenance of the hypoxene concentration; it is suitable for purposes of combination therapy.
6 dwg, 1 tbl
The invention relates to medicine, in particular to pharmacological agents, namely the TRANS-dermal patches.
Known application of drugs, representing a transdermal (skin) of therapeutic system (TTS)that allows you to adjust the speed and the quantity of injected through the skin into the overall flow of drugs. The transdermal route of administration of drugs (LV) allows to minimize the variability of therapeutic effect of stably maintaining a constant concentration of active substance in blood plasma, close to the minimum therapeutic concentration. Decreases the effect of presystemic metabolism in the liver, to apply the LP with a narrow therapeutic index and a short half-life, and also to eliminate the possibility of overdose in the initial period. There is the possibility of immediate termination of treatment TTC in case of any side effects of the drug [Andreeva I.N., Sysouev B.B., Glazkova T.U. Percutaneous delivery system of drugs in the body: the creation of medicines, the development of technology, development prospects, 2003, Mizin p. g Transcutaneous drug delivery: a Training manual. - Samara. 2004. - 124 S.; Mizin p. g, Bykov V.A., Nastin SCI, Fomenko E.A. Introduction of drug is marketed substances through the skin - achievements and prospects (review) // Herald of the Voronezh state University. Series: Chemistry. Biology. Pharmacy. No. 1, 2004. - S-183]. TTC is used for long-term treatment of chronic diseases, when the injection route of administration is not sufficiently gentle.
Usually transdermal patch includes a protective layer, the matrix layer underlying the backing layer and the matrix layer contains a mixture of existing drug substances and adhesive bounding when pressed and selected for entry into the diffusional communication with the skin (patent RF №2177311, 2379029). Backing layer can be a breathable or airtight material containing fabric, polyvinyl acetate, grades, polyethylene, polyurethane, a copolymer of ethylene and vinyl acetate, polyethylene terephthalate, polybutylene terephthalate, aluminum foil, and combinations thereof. Backing layer may be monolithic or multilayer thickness from 0.012 mm to about 0,125 mm
The matrix layer is obtained from adhesives, effective under pressure. This may be polyvinylpyrrolidone (PVP) weight K30 [Vasiliev A., Krasnik I.I., Ravikumar S. Maksymenko OO Transdermal therapeutic system with indomethacin // Chem.-Pharm. W. - 2001. - T. 35, No. 10. - P.51-52]. PVP is a polymer of N-vinylpyrrolidone. It is obtained by polymerization of a monomer - vinyl is irreligion. The patch also contains an easily removable protective layer, which is produced from polymeric materials that can be metalize, but not necessarily. Examples of polymeric materials include polyurethane, polyvinyl acetate, grades, polypropylene, polycarbonate, polystyrene, polyethylene, polyethylene terephthalate [RF patent №2379029]. Currently, the nomenclature of drugs in the form of TTC presents drugs of different pharmacological groups: angioprotectors, anticoagulants, correctors of microcirculation, narcotic analgesics, NSAIDs, hormonal drugs. TTC with antihypoxants and antioxidants are not registered. The search for drugs that protect biomacromolecule from the damaging effects of free radicals and oxidized products of lipid peroxidation (LPO)is one of the urgent problems of modern pharmacology.
Lipoxen belongs to the group of antioxidants and antihypoxants, effective for all types of hypoxia exerts anticoagulant and hypolipidemic action, has vasodilating and anti-ischemic effects, increases the body's resistance to the action of unfavorable factors used in complex treatment of diseases in the form of capsules, tablets and 7% solution in ampoules. With long-term complex treatment of chronic C the problems is rational transdermal introduction, as the injection method is traumatic in relation to the skin, and oral long way of introducing the possible manifestation of complications from gastro-intestinal tract, allergic reactions, individual intolerance [radar "encyclopedia of drugs," No. 15, 2007]. Transdermal introduction of lipoxen not previously registered.
Object of the invention is the expansion of the range TTC by creating a transdermal patch with antihypoxant and antioxidant substances for the integrated treatment of chronic diseases.
The essence of the invention lies in the fact that the proposed transdermal patch with a total area of 25 cm2representing the matrix system and includes a substrate, a matrix layer and an opaque protective coating and the matrix layer contains as a medicinal substance mixture lipoxen from 2 mg/cm2up to 4 mg/cm2and auxiliary substances, giving the band-aid adhesive properties, in the following ratio of components in the manufacture of: 6,72 wt.% substance of lipoxen, 15,11 wt.% solution of sodium metabisulfite in propylene glycol 1,2, of which 0,067 wt.% falls on sodium metabisulfite, and 56,0% by weight 95% ethyl alcohol and 22,17 wt.% PVP K30. The proposed area of the patch due to the need to provide is of not only the optimum thickness of the matrix, which according to literature data should be 210±20 μm, but the optimal breakout forces, which according to experimental data is of 1.56 N/a see
The content of lipoxen in the matrix layer from 2 mg/cm2up to 4 mg/cm2due to the fact that the direct proportional dependence of the rate of transdermal feed from the content of lipoxen in the matrix layer is maintained to achieve its contents in the matrix 100 mg or 4 mg/cm2and then ceases to depend on him. [Krivosheyev S.A., IGOR Devyatkin, Demina NB Application pharmaceutical form: Patches / Under obscured Waikawa. - M.: MAKS Press, 2005]. The protective coating should protect the drug from light and moisture, so as lipoxen - the substance is hygroscopic and reactive. Polyphenolic derivative 4-thiosulfonate easily enter into redox reactions, and the light can initiate these reactions. The proposed qualitative and quantitative composition of the matrix is optimal and provides a high degree and the constancy of the speed of releasing the drug from the patch.
The invention is illustrated by figures. Figure 1 shows the schematic illustration of the transdermal patch in the context, where 1 is the backing layer, 2 - matrix layer, 3 - layer protection.
Figure 2 - schematic of the images transdermal patch according to the invention (top and bottom view).
Figure 3 is a kinetic curve transdermal supply lipoxen from the matrix.
Figure 4 - UV spectra breeding of experienced tank through 5,22 and 25 hours of observation (highs 276,6 nm) in the study of the permeability of the skin: the countdown UV spectra from the x-axis.
Figure 5 - UV spectra of dialysate of control and experimental tanks after 2 hours of observation in the study of the permeability of the skin: on the x - axis is wavelength, on the y - axis and absorbance value.
Figure 6 - UV spectra breeding dialysate of control and experimental tanks after 24 hours of observation in the study of the permeability of the skin: 4 - range of dialysate control sample, 5 - range of dialysate prototype.
The composition of the adhesive matrix containing lipoxin: 1,2 propylene glycol, sodium metabisulfite, polyvinylpyrrolidone molecular K 30 (PVP K30 (Biochemica), ethanol 95%. The matrix layer is obtained from adhesives, effective under pressure. This may be polyvinylpyrrolidone (PVP) weight K30. PVP is a polymer of N-vinylpyrrolidone. It is obtained by polymerization of a monomer - vinylpyrrolidone.
Impervious to BAS the film-substrate (backing layer) metallized polyethylene terephthalate with a thickness of 20 μm. The protective layer in the form of siliconized paper thickness of 180-200 microns. Set the ü patch 25 cm 2.
The composition of the transdermal patch introduced excipients that performs the functions of a foaming agent, prolongator and adhesive (PVP K30), power amplifier permeability of the skin, plasticizer and solvent (propylene glycol 1,2), antioxidant (sodium metabisulfite), preservatives (ethyl alcohol 95%).
Backing layer can be a breathable or airtight material containing fabric, polyvinyl acetate, grades, polyethylene, polyurethane, a copolymer of ethylene and vinyl acetate, polyethylene terephthalate, polybutylene terephthalate, aluminum foil, and combinations thereof. Backing layer may be monolithic or multilayer thickness from 0.012 mm to about 0.125 mm [Krivosheev S.A., IGOR Devyatkin, Demina NB Application pharmaceutical form: Patches / Under obscured Waikawa. - M.: MAKS Press, 2005].
In preferred embodiments the embodiment of the adhesive matrix with the medicinal substance may contain from 2 mg/cm2up to 4 mg/cm2lipoxen. The medicinal substance is soluble in a hydrophilic matrix.
The adhesive matrix is obtained by mixing 6,72 wt.% lipoxen with 15,11 wt.% solution of sodium metabisulfite in propylene glycol 1,2, of which 0,067 wt.% falls on sodium metabisulfite, and with 56,0 wt.% 95% ethyl alcohol and 22,17 wt.% PVP K30 (based on 25 cm2/sup> ).
The patch also contains an easily removable protective layer with a thin dotted line that divides the patch into two halves with an S-shaped incision, which is produced from polymeric materials that can be metalize, but not necessarily. Examples of polymeric materials include polyvinyl acetate, grades, polypropylene, polycarbonate, polystyrene, polyethylene, polyethylene terephthalate.
Proposed transdermal patch was obtained as follows. Weighed crystalline lipoxen ground in a mechanical mortar to a particle size passing through a sieve with the hole diameter of 0.1 mm to Prepare a 0.5% solution of sodium metabisulfite in propylene glycol 1,2 by dissolving in a water bath at 60°C. In the mixer load the substance of lipoxen warmed 0.5% solution of sodium metabisulfite in 1,2 propylene glycol, ethyl alcohol 95% and PVP K30. The rotational speed of the blades 36,5:24,3 rpm is Stirred until complete dissolution of the polymer. As lipoxen not soluble in ethyl alcohol, and 1,2 propylene glycol is dissolved in the infusion for 4 hours, then the homogenization of the mixture and dissolution of the drug under the influence of the source of ultrasound (ultrasonic scalpel was URSC-7h) within 30 seconds (22-25 kHz). The obtained viscous adhesive mass with the help of the pump is pumped into the hopper m is bus sleeppromoting IVO 3220 e-01 (spreding machines). Adjust the rod to the desired thickness. Machine causes an even layer on the non-plated side metallized polyethylene terephthalate film substrate (thickness of the substrate is 20 μm). The film-substrate (backing layer) is passed through squeegee 2-3 times for more accurate and uniform application of the adhesive mass. Backing layer coated thereon an adhesive mass transfer in drying ovens, where the drying of the plaster at 20°C for 24 hours [Vasiliev A., Krasnik I.I., Ravikumar S. Maksymenko OO Transdermal therapeutic system with indomethacin // Chem.-Pharm. W. - 2001. - T.35, No. 10. - P.51-52]. Dried adhesive transdermal patch is laminated on the machine for laminating. The laminate is passed on automatic knife, cut the sheet into pieces of size 5×5 cm After drying changes the ratio of the components of the matrix, as the alcohol evaporates. In the standardization of dosage forms quantify only the content of lipoxen, which should be from 2 to 4 mg/cm2. Prepared transdermal patches are Packed in a contour buzyakova packaging according to OST 64-071-89 of paper with PVC coated or paper holodnojarivski on THE 9453-037-21032843-96, or in packages with a valve, put the instructions for use. On each box paste a label indicating the enterprises-manufacturer, its trademark, the name of the LP Latin and Russian languages, the PL composition, quantity, method of application, storage, registration number, batch number, expiry date. Bundle pack with shrink film.
Biopharmaceutical research was carried out by dialysis. On the adhesive layer of the patch (an area of 25 cm2), pasted a sample model of a biological membrane that replaces "experiencing" the skin of animals. The laminate patch containing lipoxin, the membrane was fixed in a holder and immersed in chemical beaker with 50 ml of 0.05% solution of sodium metabisulfite in phosphate buffer and thermostatically at a temperature of 37±0,5°C. the sampling dialysate (3.0 ml) was carried out after 30 minutes, 1, 2, 4, 6, 8, 12, 18, 24, 48, 72, 96, 120, 144, 168 hours with immediate return to dialysate taken of the volume of the solvent. A sample of dialysate analyzed spectrophotometrically at the wavelength range 200-380 nm. Starting with 24 hours of observation were prepared by dilution of the sample of dialysate. For this 3.0 ml of sample was placed in a flask 25.0 ml and made a solution of phosphate buffer with sodium metabisulfite to the mark. The optical density was measured on the spectrophotometer SF 2000-02 in the maximum absorption (305±2 nm). The layer thickness of 10 mm Parallel to the measured optical density of the control sample. As the reference solution used 0.05% solution of sodium metabasalt the same phosphate buffer. The content of lipoxen in dialysate expected considering breeding RNO. The results of biopharmaceutical studies presented in the table. In the first 8 hours was observed gradual decrease in velocity lipoxen. Further, the feed rate was changed pulse sequence with increasing or decreasing values. The constancy of the velocity of the release of the matrix was observed from 48 to 168 hours, the average speed of the feeder lipoxen in this period amounted to 1.48±0.5 μg/h·cm2the maximum degree of liberation of lipoxen reached 168 hour 23,69%. For calculation of the rate of transdermal supply lipoxen from the matrix through a model membrane curves according to the number of released drug substance (μg/cm2) time (h) (figure 3). The feed rate of lipoxen of the matrices was determined as the tangent of the angle of inclination of the stationary plot line. As experimental models for studying the permeability of the skin in vitro was used facing the skin of rats. For holding biopharmaceutical research from the surface of the back of rats (n=6) were carefully removed the coat. The flaps of skin were freed not only from subcutaneous fat, and a layer of the hypodermis, richly permeated by a network of capillaries. Checked the flap under a magnifying glass on the entire surface of the epidermis was placed between DV is sanitary napkins, well moistened with saline, and transferred into a Petri dish. The experiments were set immediately after the capture material. The test patch area of 2 cm2similarly inflicted on the skin of the animal, pre-moistened with water. The permeability of the isolated skin was determined using dialysator. In parallel had a control experience. Skin served as a membrane separating the patch with lipoxinol and environment for dialysis. As the dialysis environment used isotonic 0.9% sodium chloride solution volume of 50 ml Dialysis was performed in a thermostat at a temperature of 37±0,5°C. the sampling dialysate produced after 1 hour of observation. The volume of fluid selected for the sample (3 ml), return the same volume of isotonic sodium chloride solution. The liquid for this purpose was in thermostat together with dialysator to maintain the temperature of the experiment. After 24 hours of observation were prepared by dilution of dialysate to the selected samples (3.0 ml) was added to 7.0 ml of isotonic sodium chloride solution. Recorded UV spectra in the wavelength range 200-380 nm (shoulder 303-307 nm). Skin proteins have their own absorption in the region of 230-300 nm and interfere with the detection of lipoxen. Absorption maxima in the experimental and control tanks (276±2 nm) did not differ from each other and testified vysvobozhdenijah proteins of the hypodermis in experiments in vivo, as well as the in vitro experiments in the first 6 hours of observation (figure 4). The distinguishing features between the UV spectra of (position of extrema) breeding experimental and control tanks were not fixed. 6 hours surveillance significant differences of the values of optical density experienced (D.) and control samples (D.) have been identified (figure 5). After 6 hours from the start of the experiment, the observed differences in the values of optical density at 305±2 nm. With 24 hours has seen a sharp increase in values D., exceeding values D. 2.3 times (figure 6).
Further values D. was not significantly changed, while the values D. grew during the subsequent observation period. On the 2nd day of the experiment recorded blue-green coloration of dialysate prototype in contrast to the control.
To quantify the extent of the release and penetration of lipoxen imposed crafted plaster on cleansed from wool and gidratirovannuyu the skin of male rats (n=6) with an area of 5 cm2(the content of lipoxen 10 mg) for 2 days of the experiment. After a time the observations were made flush with the surface of the skin purified water. Put the solution in the flask of 250.0 ml, drove up to the mark given solvent, 5 ml of the dilution was placed in a flask 25.0 ml and brought to match is. Filtered dilution was analyzed spectrophotometrically at the wavelength range 200-380 nm as the reference solution used purified water. Taking into account technological losses when designing the patch on the skin surface after 48 hours of observation, it was found 92,50±2% of lipoxen.
Polyphenols belong to the rejuvenating agents. Lipoxen is a polyphenol - derived and their structure can contain up to 12 hydroxyl groups. In an alkaline environment while interacting with some reagents polyphenols have blue color.
A sharp increase in the values of D prototype with 24 hour surveillance is probably connected with the fact that released lipoxen as polyphenolic compound enters the polyphenol-protein interactions with the formation of a white precipitate, and dialysate in the experimental tank more turbid than in the control, as indicated, and the value of optical density. Further increase in the concentration of lipoxen in dialysate increases values D. through further education polyphenol-protein complex in the form of sediment. Blue-green coloration of dialysate experienced tank through a 3 day observation indicates a possible running reactions polyphenolic compounds in an alkaline environment.
Thus, the present invention can OS which may serve as a basis in many variations, a specialist in the art can deduce from the above description. All such variations and modifications are covered by the scope and essence of the present invention.
Transdermal patch for administering lipoxen has the following advantages:
In comparison with oral assignment allows you to provide a more rapid action of drugs.
- Makes it possible to avoid the problems associated with oral administration: inactivation or reduced activity of the drug in the first passage and gastric metabolism, as well as the related adverse reactions.
- Improves the compliance of patients (easy and noninvasive method of using the drug).
|0,5 (0-0,5 h)||1 h (0.5-1 h)||2 hours (1-2 hours)||4 hours (2-4 hours)||6 hours (4-6 h)||8 hours (6-8 hours)||12 hours (8-12 h)||18 h (12-18 h)|
|V µ g/h·cm2||32,82||28,16||7,38||7,12||6,21||0,98||5,24||14,08|
|24 hours (18-24 h)||48 hours (24-48 h)||72 hours (48-72 h)||96 h (72-96 h)||120 h (96-120 h)||144 h (120-144 h)||168 h (144-168 h)|
|V µ g/h·cm2||12,18||of 2.21||1,48||1,47||1,49||1,50||1,48|
|Note - Δ=±0,5|
Amount (mg/cm2), the degree of release (%) and speed transdermal supply lipoxen (µg/h·cm2from the patch with lipoxinol for 168 hours while conducting biopharmaceutical studies in vitro.
Transdermal patch representing a matrix system that includes a backing layer, the matrix layer comprising a mixture of existing drug substances and excipients, giving the band-aid adhesive properties, characterized in that it has an opaque protective coating, and the drug matrix layer is lipoxen in the amount of 2 m is/cm 2up to 4 mg/cm2in the following ratio of components in the manufacture of: 6,72 wt.% substance of lipoxen, 15,11 wt.% restore sodium metabisulfite in propylene glycol - 1,2, of which 0,067 wt.% falls on sodium metabisulfite, and 56,0% by weight ethanol 95%and 22,17 wt.% PVP K30, the total area of the patch is equal to 25 cm2.
SUBSTANCE: invention relates to novel crystalline forms of 3-[[3,5-dribromo-4-[4-hydroxy-3-(1-methylethyl)phenoxy]phenyl]amino]-3-oxopropanoic acid, characterised by X-ray powder diffraction pattern with principal peaks either at 2θ = 16.1 ± 0.2, 20.1 ± 0.2, 20.7 ± 0.2, and 24.2 ± 0.2, or at 2θ = 9.0 ± 0.2, 14.7 ± 0.2, 19.6 ± 0.2, 21.6 ± 0.2 and 24.3 ± 0.2. The invention also relates to methods of obtaining the disclosed crystalline forms, a pharmaceutical composition having thyroid beta-receptor agonist properties, a method for selective agonist action on thyroid beta-receptor, use of said forms to produce a medicinal agent and a method of treating mammals suffering from thyroid dysfunction associated conditions.
EFFECT: obtaining novel crystalline forms of 3-[[3,5-dribromo-4-[4-hydroxy-3-(1-methylethyl)phenoxy]phenyl]amino]-3-oxopropanoic acid, having thyroid beta-receptor agonist properties.
19 cl, 3 tbl, 7 ex
SUBSTANCE: invention refers to experimental medicine and can be used for developing molecular methods of treating coronary insufficiency. For this purpose, the simulated myocardial ischemia requires experimental myocardial injections of an endotheliocyte growth factor gene in the form of the phVEGF165 vector at 50-100 mcg/cm2 of an ischemic region at an area pitch of 5 mm. 2-dimethylaminoethanol is added to the vector preparation to provide more effective myocardiocyte transfection.
EFFECT: unlike peptide growth factors requiring the regular administration, the use of a gene construct with the endotheliocyte growth factor gene introduced in a single dose according to the developed method provides the intensified myocardial construct delivery and the activation of a greater number of cells involved in angiogenesis that promotes repaired perfusion in the ischemic myocardium region.
2 ex, 4 tbl
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to medicine, pharmacology and biology and concerns application of Trecresan as an agent to decrease cholesterol esterase activity.
EFFECT: invention allows extending the range of agents used to decrease cholesterol esterase activity.
4 tbl, 2 ex
SUBSTANCE: invention relates to novel substituted methyl-amines of general formula 1, having serotonin 5-HT6 receptor antagonist properties. In formula 1 , W is naphthalene, indolysin or quinoline; R1 is hydrogen, fluorine, chlorine, methyl; R2 is hydrogen, fluorine, methyl, phenyl, thiophen-2-yl, furan-2-yl, pyridyl, piperazin-1-yl or 4-methylpiperazin-1-yl; R3 is methyl; or W is benzene, R3 assumes the value given above; R1 is 3-Cl, R2 is 3-piperazin-1-yl or 3-(4-methylpiperazin-1-yl); or R1 is hydrogen, R2 is phenyl or pyridyl; or R1 is hydrogen, fluorine, chlorine, methyl; R2 is 4-piperazin-1-yl or 4-(4-methylpiperazin-1-yl); or W is oxazole, R3 is optionally substituted methyl; R1 is chlorine or fluorine, R2 is methyl, or R1 is hydrogen, fluorine, chlorine, methyl; R2 is piperazin-1-yl, 4-methylpiperazin-1-yl, or R1 is chlorine, fluorine or methyl; R2 is furan-2-yl, or R1 is hydrogen, fluorine, chlorine, methyl; R2 is furan-2-yl, R3 is (tetrahydrofuran-2-yl)methyl, or R1 is hydrogen, fluorine, chlorine, methyl; R2 is thiophen-2-yl, R3 is 2-methoxyethyl, or R1 is chlorine or fluorine, R2 is thiophen-2-yl, R3 is methyl.
EFFECT: compounds can be used to treat central nervous system (CNS) diseases, such as psychiatric disorders, schizophrenia, anxiety disorders, as well as for improving mental capacity, for treating obesity or for studying the molecular mechanism of inhibiting serotonin 5-HT6 receptors.
15 cl, 27 dwg, 2 tbl, 25 ex
SUBSTANCE: compounds activate glucokinase and can be used to prepare medicine for treating of metabolic disorders, for lowering blood glucose level, for treating hyperglycemia, for treating IGT, for treating Syndrome X, for treating impaired fasting glucose (IFG), for treating type 2 diabetes, for treating type 1 diabetes, for delaying the progression of impaired glucose tolerance (IGT) to type 2 diabetes, for delaying the progression of non-insulin requiring type 2 diabetes to insulin requiring type 2 diabetes, for treating dyslipidemia, for treating hyperlipidemia, for treating hypertension, for lowering food intake, for appetite regulation, for for treating obesity, for regulating feeding behaviour, or for enhancing the secretion of enteroincretins. In compounds of formula , A denotes , R3 is selected from a group consisting of phenoxy and benzyloxy, each possibly substituted with one or more substitutes independently selected from R12; R12 is F, CI, Br, -CF3, -CN methyl, ethyl, isopropyl, tert-butyl, methoxy, methylthio, ethoxy, cyclopropyl-methoxy, -NHC(O)CH3 or -S(O)2-CH3; R30 is methyl, ethyl, propyl, isopropyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, methoxy, ethoxy, propoxy, butoxy, tert-butoxy, benzyloxy or cyclopropyl-methoxy, each possibly substituted with one or more substitutes independently selected from R12; R8 is methylthio, isopropylthio, ethylthio or 2-methylpropylthio, each substituted with one or more substitutes independently selected from R34; R34 is carboxy.
EFFECT: improved properties of the compound.
13 cl, 1 tbl, 242 ex
SUBSTANCE: invention is used for treatment venous malformations, administered by means of injections. The declared preparation contains ethanol with the degree of cleanliness from 70 to 99 % which is necessary for the effect causing sclerosis, a difficult ethyl ester of the iodated fat acid, and in addition contains ethyl cellulose or dextrin, providing viscosity of the solution from 10 to 700 cPz, for the preparation of gel with the emboli effect.
EFFECT: declared drug provides reliable application at all stages of course of the treatment and ability to formation of a selective steady sclerosis, also the invention provides biological compatibility, high ability to densifying, formation of biodegrading derivatives, an exception of local or system toxic effects.
6 cl, 1 tbl, 2 ex
SUBSTANCE: invention refers to new compounds of formula (I) where X is carboxylic acid, carboxylates, carboxylic anhydride, diglyceride, triglyceride, phospholipid, or carboxamides, or to any their pharmaceutically acceptable salt. The invention particularly refers to (4Z, 7Z, 10Z, 13Z, 16Z, 19Z)-ethyl 2-ethyldocosa-4,7,10,13,16,19-hexanoate. The invention also refers to a food lipid composition and to a composition for diabetes, for reducing insulin, blood glucose, plasma triglyceride, for dislipidemia, for reducing blood cholesterol, body weight and for peripheral insulin resistance, including such compounds. Besides, the invention refers to methods for treating and/or preventing diabetes, dislipidemia, peripheral insulin resistance, body weight reduction and/or weight gain prevention, insulin, blood cholesterol, blood glucose and/or plasma triglyceride reduction.
EFFECT: higher clinical effectiveness.
61 cl, 4 tbl, 16 dwg, 5 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to compounds of general formula
where R1 represents CH3; R2 represents halogeno or CN; R3 represents H or CH3; R4 represents H or CH3; n represents 0, 1 or 2; and to their pharmaceutically acceptable salts. Also, the invention refers to a pharmaceutical composition and to application of the compounds of formula (I) in preparing a drug exhibiting antagonist activity in relation to CX3CR1 receptor.
EFFECT: provided the compounds of formula (I) as CX3CR1 receptor antagonists.
20 cl, 1 tbl, 3 dwg, 10 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: present inventions refers to a new crystalline form of tetomilast hydrate of the X-ray powder diffraction spectrum having characteristic peaks at the angle 20=10.6°, 12.9°, 21.1°, 22.3° and 25.0°, to a new crystalline form of anhydrous tetomilast type C of the X-ray powder diffraction spectrum having characteristic peaks at the angle 2θ=4.2°, 8.2°, 12.0°, 16.4°, 24.7° and 25.9°, to a new crystalline form of acetonitrile tetomilast solvate of the X-ray powder diffraction spectrum having characteristic peaks at the angle 2θ=3.6°, 7.1°, 10.6°, 14.2° and 24.8°, to based pharmaceutical compositions and to methods for preparing.
EFFECT: new crystalline forms shows useful processing characteristics with relation to preparing pharmaceutical drugs of them.
13 cl, 14 dwg, 8 ex
SUBSTANCE: present invention is related to new quinolone derivatives of general formula (I) where R1: C3-6cycloalkyl or lower alkylene C3-6cycloalkyl, R2: -H or halogen, R3: -H, halogen, -OR0 or -O-(lower alkylene)-phenyl, R0: are the same or different from each other, and each represents -H or lower alkyl, R4: lower alkyl, halogen(lower alkyl), lower alkyleneC3-6cycloalkyl, C3-7cycloalkyl or a heterocyclic group, where cycloalkyl and the heterocyclic group specified in R4 can be respectively substituted, R5: -NO2, -CN, -L-Ra, -C(O)R0, -O-Rb, -N(R6)2, lower alkylene-N(R6)(Rc), -N(R6)C(O)-Rd, lower alkylene-N(R6)C(O)-Rd, lower alkylene-N(R0)C(O)O-(lower alkyl), -N(R0)C(O)N(R0)-Re, lower alkylene-N(R0)C(O)N(R0)-Re, -N(R0)S(O)2N(R0)C(O)-Rd, -CH=NOH, C3-6cycloalkyl, (2,4-dioxo-1,3-thiazolidin-5-yliden)methyl or (4-oxo-2-tioxo-1,3-thiazolidin-5-yliden)methyl where cycloalkyl specified in R5 can be respectively substituted, R6: H, lower alkyl, lower alkylene-CO2R0 or lower alkylene-P(O)((OPp)2, where lower alkylene specified in R6 can be substituted, L: lower alkylene or lower alkenylene which can be respectively substituted, Ra: -OR0, -O-(lower alkylene)-phenyl, -O-(lower alkylene)-CO2R0, -CO2R0, -C(O)NHOH, -C(O)N(R6)2, -C(O)N(R0)-S(O)2-(lower alkyl), -C(O)N(R0)-S(O)2-phenyl, -C(O)N(R0)-S(O)2-(heterocyclic group), -NH2OH, -OC(O)R0, -OC(O)-(halogen(lower alkyl)), -P(O)(ORp)2, phenyl or the heterocyclic group where phenyl or the heterocyclic group specified in Ra can be substituted, Rp: R0, lower alkylene-OC(O)-(lower alkyl), lower alkylene-OC(O)-C3-6cycloalkyl, lower alkylene-OC(O)O-(lower alkyl), Rb: H, lower alkylene-Rba or lower alkenylene-Rba where lower alkylene or lower alkenylene specified in Rb can be substituted, Rba: -OR0, -CO2R0, -C(O)N(R0)2, -C(O)N(R0)-S(O)2-(lower alkyl), -C(O)N(R0)-S(O)2-[phenyl, -C(NH2)-NOH, -C(NH2)=NO-C(O)-(lower alkylene)-C(O)R0, -CO2-(lower alkylene)-phenyl, -P(O)(ORp)2, -C(O)R0, -C(O)-phenyl, C3-6cycloalkyl, phenyl or the heterocyclic group where phenyl and the heterocyclic group specified in Rba can be substituted, Rc: H, lower alkylene-OR0, lower alkylene-CO2R0, lower alkylene-P(O)((OPp)2, phenyl where lower alkylene and phenyl are specified in Rd can be substituted, Rd: C1-7-alkyl, lower alkenyl, halogen(lower alkyl), lower alkylene-Rda, lower alkylenylene-Rda, C3-6cycloalkyl, phenyl, naphthyl or the heterocyclic group, where lower alkylene, cycloalkyl, phenyl, naphthyl and the heterocyclic group specified in Rd can be substituted, Rda: -CN, -OR0, -O-(lower alkylene)-CO2R0, -O-naphthyl, -CO2R0, -CO2-(lower alkylene)-N(R0)2, -P(O)(ORp)2, -N(R6)2, -C(O)N(R0)-phenyl, -C(O)N(R0)-(lower alkylene which can be used by -CO2R0)-phenyl, -N(R0)C(O)-phenyl, -N(R0)C(O)-OR0, -N(R0)C(O)-O-(lower alkylene)-phenyl, -N(R0)S(O)2-phenyl, C3-6cycloalkyl, phenyl, naphthyl or the heterocyclic group, where phenyl, naphthyl and heterocyclic group specified in Ra can be substituted, Re: lower alkylene-CO2R0, phenyl, -S(O)2-phenyl or -S(O)2-(heterocyclic group), where phenyl and the heterocyclic group specified in Re can be substituted, X: CH, A: C(R7), R7: -H, or R4 and R7 together can form lower alkylene, where the substituted groups have the substituted specified in cl.1, and provided 7-(cyclohexylamino)-1-ethyl-6-fluor-4-oxo-1,4-dohydroquinoline-3-carbonitryl is excluded. Also, the invention refers to a pharmaceutical composition based on a compound of formula (I) and application of formula (I) for preparing a thrombocyte aggregation inhibitor or a P2Y12 inhibitor.
EFFECT: there are produced new quinol-4-one derivatives showing effective biological properties.
11 cl, 83 tbl, 71 ex
SUBSTANCE: invention refers to high-molecular compounds for medical purposes. Water-soluble polymeric complexes of antiviral agent arbidol of general formula: are described, where: Arb - arbidol: ethyl ester 6-bromo-4-dimethyl-aminometil-1-methyl-5-oxy-2-feniltiometilindolinil-3-carboxylic acid hydrochloride monohydrate; m1=100-(m2+m3) mol %; m2=(7.6-9.8) mol %; m3=(11.5-13.6) mol %; content of Arb=26.4-32.1 wt %.
EFFECT: obtained water-soluble polymeric complexes of arbidol may find application in pharmacology, as they can serve as basis for new effective and safe antiviral drugs and their dosage forms.
1 cl, 6 ex, 4 tbl, 2 dwg
SUBSTANCE: novel biomaterials consist of combination of sulphated hyaluronic acid and deacetylated hellane for application as highly efficient barrier for prevention of post-operation commissures in operation in abdominal, pelvic areas and, first of all, on spine.
EFFECT: increase of application efficiency.
16 cl, 1 dwg, 2 tbl, 6 ex
SUBSTANCE: method involves drying injured zone after having removed dental deposit and additional treating cement surface in inflammation zone with citric acid solution of 0.1 mMole/l concentration during 5 min, and then with 0.06% Chlorohexidine solution and Nikiforov mixture. Sulfacrylate is placed into periodontium pocket as glue periodontial bandage and the lesion focus is treated with ultrasound of 26.5 kHz during 3 s.
EFFECT: accelerated treatment course; activated reparative processes in periodontium; improved mechanical strength; accelerated polymerization in glue bandage.
FIELD: medicine, pharmaceutics.
SUBSTANCE: claimed invention relates to chemical-pharmaceutical industry and deals with medication, obtained by interaction of selenium-containing compound with alpha, alpha-dichlorcarboxylic acid, stabilised by nitric acid in amount not more than 5 wt %. As selenium-containing compound in interaction used is solution of selenious acid in amount not more than 20.0 wt %. Medication can additionally contain dimethylsulfoxide in amount 5-20%. Method of obtaining medication is realised by interaction of selenium-containing compound with alpha, alpha-dichlorcarboxylic acid, stabilised by nitric acid in amount not more than 5 wt %, and as selenium-containing compound in interaction used is solution of selenious acid in amount 0.5-20.0 wt % and interaction is realised at temperature not higher than 70°C. In application of medication for treatment of benign, viral, pre-malignant and malignant non-metastatic skin lesions, dysplastic lesions of visible mucous membranes and other skin lesions, it is applied on lesion nidus on the 1, 2-3, 7-9 and 22-24 days of treatment.
EFFECT: medication possesses higher stability and efficiency.
8 cl, 4 ex, 3 tbl