Method for production of coated tablets having cerebroprotective, antioxydant, and noothropic action
SUBSTANCE: claimed method includes blending of active base and auxiliary ingredients to form tablet corn, representing composition of sugar powder, monocrystalline cellulose, vinylpyrrolidone and calcium stearate; humidifying of obtained mixture; drying of obtained granules; dry granulation through granulator with standardized holes; pelletization of standardized granules to produce tablet corn; and coating. Mixture is humidified with 5-7 % starch mucilage in starch mucilage/humidifying mixture mass ratio of 1:25-30, wherein mixture is blending with starch mucilage for homogeneous distribution wet in whole mass.
EFFECT: tablets with increased hardness and enhanced pharmacological activity.
2 cl, 2 ex
The invention relates to medicine, in particular to pharmacotherapy, namely cerebroprotective, antioxidant, neuroprotective drugs with combined active base in coated tablets, and their manufacturing techniques.
Known nootropic drug tablets "piracetam", registration No. 95/174/6/82/624/24 from 29.09.95, (drugs of Ukraine, 1999-2000, 2, str-306).
Piracetam has a positive effect on metabolism, blood flow and bioenergetic processes.
The disadvantages of the known medicines are not has an antioxidant effect, slow pharmacological effect, manifested only in an hour, a limited range of pharmacological activity, the possibility of acute coronary insufficiency and the occurrence of dyspeptic symptoms.
In addition, the technology of manufacturing of tablets piracetam provided by mixing an active basis with auxiliary ingredients, moisturizing mixture, wet granulation, drying of granules, dry granulating calibrated granulator and pressing tablets-cores.
This increases costs and reduces the productivity of the manufacture of tablets.
Known cerebroprotective, antioxidant and nootropic drug in tab is edah coated on declarative patent of Ukraine # 55983 And, class a 61 K 31/40, a 61 K 31/41.
Known drug as an active Foundation contains a mixture of piracetam with thiotriazoline, as well as other ingredients to form the tablet core and shell powdered sugar, microcrystalline cellulose, polivinilpirolidon, oximeter cellulose, stearic acid or calcium stearate, and polyethylene oxide.
Pharmacological advantages of well-known medicinal product is due to vzaimopodderzhivayuschimi action thiotriazoline, which possesses antioxidant and cerebroprotective action, and piracetam, which owns nootropic action, along with metabolic regulatory mechanism of blood circulation contributes to the nervous mechanism of its regulation, increases the speed and force of impact of medicines on improvement of blood supply.
When this drug is not only preserves, but also expands the range of pharmacological effects, inherent thiotriazoline, and eliminates the aggravation of coronary insufficiency and dyspeptic phenomena, possible when using piracetam.
A disadvantage of the known means is, as in the above analogy, the need for surgery wet granulation in the manufacture of tablets.
A method of obtaining antiaggregative tools, improving the surrounding cerebral circulation, according to the patent of Russian Federation №2157209, class a 61 K 31/522.
The known method involves mixing the active base with auxiliary ingredients to form tablet cores, representing the composition of powdered sugar, microcrystalline cellulose, polyvinylpyrolidone; wetting the mixture with distilled water or starch paste when the mass ratio of the humidifier to irrigated mass 1:1,8-3,0; implementation of wet granulation, drying, dry granuliruta; the introduction of a salt of stearic acid and talc and the subsequent formation of granules into tablets-core; applying them to the shell.
This method is taken as a prototype of the proposed method to obtain drugs in the form of film coated tablets.
The disadvantages of this method are the wetlands of the mixture, excluding the arbitrary formation of various size granules in the process of moisture directly into the mixer, the increase in time duration of drying the wet granules; lack of firmness on the crushing ready tablets and a limited range of pharmacological actions.
The basis of the invention tasked to develop a method of manufacturing a coated tablets, providing technological advantages and improving the quality of the finished product in comparison with the analogues and the prototype.
The solution of this problem provides a method of manufacturing a coated tablets with cerebroprotective, antioxidant and neuroprotective effect, comprising mixing an active Foundation - piracetam and thiotriazoline and other ingredients to form the tablet core, which is the composition of powdered sugar, microcristalina cellulose, polyvinylpyrolidone and calcium stearate, moistening the mixture, drying, dry granuliruta calibrated through a pelleting, tableting granules into tablets-engine and transmission to the step of applying the membrane, and the moisture of the mixture to produce 5-7% starch paste at a mass ratio of paste to the humidified mixture of 1:25-30, stirring the mixture with a paste to the uniform distribution moisture throughout the mixture.
For the use of starch paste, with an initial moisture content of 1.8 to 2.2%.
In the solution for deposition of a coating on the tablet core using oxytropidoceras, titanium dioxide, tween-80, polivinilpirolidon and tartrazine.
Pharmacological and technological advantages of the method according to the invention:
a) reduction of production costs by combining the steps of wetting, wet granulation and reduce drying time;
in) strength (not less than 40 Newtons);
d) wynikamitest, namely, high solubility in water (more than 75% in 45 minutes);
d) the homogeneity of the mass.
The essence of the invention can be illustrated by the following examples of technological processes.
Example 1. Composition and production technology tablets-cores
The number of active substances and excipients, taken for the production of tablets-cores in kg:
|Calcium stearate or acid|
Refined sugar is ground in the mill. Piracetam, thiotriazoline, powdered sugar, calcium stearate, MCC and PVP is stirred for at least 3 minutes. The resulting mixture is humidified 6% starch paste (0.9 kg) and continue to mix for at least 5 minutes. The mass is dried at a temperature of 40°±2°With up to a residual moisture 2-3%. The dried granules are passed through a granulator to the diameter of the holes in the grid of 1.5-2 mm Table which aims to spend on a tablet machine RTM-41.
The average weight of the tablets is in the range of 0.333-0,368 g; solubility more than 75% in 45 minutes and strength of 40 Newton.
Example 2. The composition and coating technology tablets-cores
Ingredients for coating 25 kg of tablet cores shell:
|Oksipropilmetiltselljulozy (OPMC-606)||397,71 g|
|Titanium dioxide||with 46.6 g|
|Polyvinylpyrolidone (PVP)||150,86 g|
|Purified water||11,8 kg|
Preparation system for coating tablets-cores: 397,71 g OPMC-606 fill of 5 kg of boiling purified water, 3-4 hours after complete swelling OPMC the mixture was diluted with 2.8 kg of purified cold water. In parallel, prepare a solution of PVP 150,86 g PVP and 3 kg of purified water when heated. Pound in a mortar 46,6g titanium dioxide with 87,77 g of tween-80 and wash 0.7 kg purified water, 2,74 g tartrazine dissolved in 0.3 kg purified water. Prepared solutions OPMC, PVP and tartrazine mix, add a mixture of titanium dioxide with a twin-80, which wash 0.7 kg of purified water. The resulting mixture was filtered through gauze.
Coating of tablets is carried out in the apparatus pseudotype the layer at a temperature of 90-95° (Coverage). The feed rate of film-forming mixture of 400 ml per minute. After the filing of the whole mixture for coating tablets is maintained at the same temperature for drying.
The finished tablets unload and after cooling packaged. The obtained tablets are yellow in color.
Average weight is within 0,338-0,374, the solubility of not less than 75% in 45 minutes and strength of 40 Newton.
1. A method of manufacturing a coated tablets with cerebroprotective, antioxidant and neuroprotective effect, comprising mixing an active Foundation - piracetam and thiotriazoline and auxiliary ingredients to form the tablet core, which is the composition of powdered sugar, microcrystalline cellulose, polyvinylpyrolidone and calcium stearate, moistening the mixture, drying, dry granuliruta calibrated through a pelleting, tableting granules into tablets-engine and transmission to the step of applying the membrane, and the moisture of the mixture to produce 5-7% starch paste at a mass ratio of paste to the humidified mixture of 1:25-30, stirring the mixture with a paste to the uniform distribution of moisture throughout the mixture.
2. The method according to claim 1, characterized in that for the preparation of paste used potato starch with an initial moisture content of 1.8 to 2.2%.
3. The method according to claims 1 and 2, characterized in that when s is gotowka solution for deposition of a coating on the tablet core oksipropilmetiltselljuloza pour boiling water in the ratio 1:12-13, maintain 3-4 h until complete swelling oksipropilmetiltselljulozy, diluted with cold water in the ratio of dry mass oksipropilmetiltselljulozy to cold water 1:7-8, fray carefully tween-80 and titanium dioxide in a ratio of 1:1,8-2, transfer the mixture into a solution of oksipropilmetiltselljulozy, separately poured cold water polivinilpirolidon in the ratio of 1:19-20, heated to complete dissolution of polyvinylpyrolidone, cooled, poured into a solution of oksipropilmetiltselljulozy, dissolve tartrazine in warm water at a ratio of 1:109-110, making the solution in the solution oksipropilmetiltselljulozy, carefully mix the resulting solution is filtered through two layers of cheesecloth and transfer to the stage applying a coating on the tablet core.
FIELD: experimental medicine.
SUBSTANCE: in rabbits one should induce hepatic ischemia due to occlusion of hepato-duodenal ligament for 30 min. Moreover, reamberin should be introduced at the dosage of 35 ml/kg during the whole period of occlusion, and at the dosage of 5 ml/kg for 10 min after removing the above-mentioned occlusion. The method provides preventing the death of experimental animals in case of ischemic exposure being harmful for this type of animals.
EFFECT: higher efficiency of protection.
SUBSTANCE: method involves applying traditional treatment and additionally administering 2 ml of 1% emoxipin solution electrophoresis to epigastric zone at acute stage end daily during 10 days.
EFFECT: accelerated inflammation relief and uterine mucous membrane recovery.
FIELD: medicine, veterinary science.
SUBSTANCE: it is suggested to apply indometophen known previously as a radioprotector. It has been established that application of indometophen at different terms within the first 4 d after irradiation helps to increase survival rate and affect positively the flow of reparative processes in the body at no side effects.
EFFECT: higher efficiency of therapy.
SUBSTANCE: the present innovation deals with obtaining biologically active substances of protein nature out of cereals, moreover it is necessary to isolate a stress separating protein 310 and/or protein being immunochemically similar to that as coarse and/or finely purified extract of the target product. For this purpose one should destruct cellular walls of 3-7-d-aged sprouts due to homogenization to isolate cell-free extract due to centrifuging which should be supplemented with a reagent-precipitator at the first stage under certain conditions to obtain residue followed by isolating a liquid phase which should be subjected to the second of impact with reagent-precipitator under certain conditions, then residue should be separated against a liquid phase due to centrifuging, and an obtained coarsely purified extract of target product should be separated against reagent-precipitator due to dialysis due to the impact of fine purification by gel filtration, if necessary. Moreover, one should conduct this procedure at certain temperature mode, and , if necessary, the extract of target product should be freeze dried. The suggested biologically active substance provides efficient regulation of body energy balance.
EFFECT: higher efficiency.
8 cl, 3 ex
SUBSTANCE: invention proposes use of polysorb as drug with membrane-stabilizing efficacy supplementing early known antioxidant and sorption properties of this substance.
EFFECT: enabled use of polysorb for monotherapy to treat a large number of diseases.
FIELD: organic chemistry, medicine, pharmacy.
SUBSTANCE: invention relates to biologically active compounds. Agent represents 3,6-dioxocyclohexa-1,4-diene-1,2,4,5-tetrasulfonate sodium. The new agent elicits antioxidant properties and therefore it can be used in food industry, in pharmaceutical compositions and cosmetic products. Also, the new agent elicits antiviral activity owing to it can be used as both the independent medicinal agent and in compositions with other preparations used for treatment of viral infections.
EFFECT: expanded assortment of medicinal agents and antioxidants, realization of indicated prescription.
1 tbl, 8 dwg
FIELD: organic chemistry, medicine, chemical-pharmaceutical industry, pharmacy.
SUBSTANCE: invention relates to a new agent with expressed selective activity with respect to central muscarinic acetylcholine receptors belonging to subtype M1. Agent represents 1-phenyl-1-(1'-methylcyclopentyl)-4-piperidino-2-butyne-1-ol hydrochloride of the formula (1) known early as low toxic cholinolytic. Agent expands a set of ligands used in research of mechanisms of the central nervous system function. Agent shows high capacity for penetration through blood-brain barrier, low toxicity and high effectiveness.
EFFECT: valuable medicinal properties of agent.
FIELD: organic chemistry, medicine, pharmacy.
SUBSTANCE: invention relates to new derivatives of 3-hydroxypiperidine of the general formula (I): wherein R means (a): -C(O)(CH2)nC(O)OH; (b): wherein R1 means -N(R2)(R3); each R2 and R3 means hydrogen atom, lower alkyl or cyclic tertiary amine; (c): -P(O)(OH)2 or (d): -C(O)(CH2)n and -NHC(O)(CH2)nN(R2)(R3) wherein n means a whole number 1-4. Indicated compounds can be used as prodrugs in preparing medicinal agents used in treatment of diseases associated with blocking agents for receptors of subtype NMDA.
EFFECT: valuable medicinal properties of compounds and composition.
10 cl, 1 tbl, 20 ex
FIELD: medicine, pediatrics, psycho-neurology.
SUBSTANCE: the present innovation deals with applying preparation that normalize energy exchange. For this purpose it is necessary to introduce L-carnitine at the dosage of 20-30 mg/kg/d in three stages, coenzyme Q10 at the dosage of 30-60 mg/d once and limontar at the dosage of 10 mg/kg/d once during the first half of the day for 2 mo twice annually. The present innovation provides improved values for nervous-psychic development due to correcting mitochondrial alterations.
EFFECT: higher efficiency of therapy.
FIELD: organic chemistry of heterocyclic compounds, biology, medicine, pharmacy.
SUBSTANCE: invention relates to new substituted pyrido[4',3':5,6]pyrano[2,3-d]pyrimidines of the general formula (1): or (2): or their pharmaceutically acceptable salts, N-oxides or hydrate possessing physiologically active properties, in particular, eliciting ability to induce apoptosis in tumor cells causing their death. In the general formula (1) or (2) X represents sulfur or oxygen atom; Y represents sulfur atom, group -SO, group -SO2, group -NH or group -NR6; R1 represents aryl, substituted aryl, heteroaryl; R2 and R5 represent hydrogen atom, alkyl, allyl, substituted benzyl, group -CH2-C(O)R3, group -CH2-C(O)NR3R4 wherein R3, R4 and R6 represent inert substitute. Also, invention relates to new combinatory libraries for search compound-leaders and candidates for medicinal compounds preparing by screening the combinatory libraries.
EFFECT: valuable medicinal properties of compounds.
9 cl, 1 tbl, 9 ex
FIELD: organic chemistry, biochemistry, medicine, pharmacy.
SUBSTANCE: invention relates to new derivatives of pyridopyrimidines of the formula (I): or (II): wherein Z means nitrogen atom (N) or -CH; W means -NR2; X1 means oxygen atom (O), -NR4 (wherein R4 means hydrogen atom or alkyl), sulfur atom (S) or -CR5R6 (wherein R5 and R6 mean hydrogen atom); X2 means oxygen atom (O); Ar1 means unsubstituted or substituted phenyl; R2 means hydrogen atom, alkyl or acyl; R1 means hydrogen atom, alkyl, halide alkyl and others; R3 means alkyl; cycloalkyl and others; R8 and R9 mean hydrogen atom, alkylsulfonyl and others, and to their pharmaceutically acceptable salts, and to intermediate compounds that are used for preparing compounds of the formula (I) and (II). Indicated compounds show inhibitory activity with respect to activity of p38 kinase and can be used in preparing a medicine agent for treatment of p38-mediated disturbances.
EFFECT: improved preparing methods, valuable medicinal properties of compounds and composition.
38 cl, 3 tbl, 116 ex
FIELD: medicine, psychiatry, neurology.
SUBSTANCE: the present innovation deals with treating affected amnestic functions in women after uterine and adnexal extirpation. For this purpose, after a 7-d-long introduction of estradiol as suppositories at curative dosage of 8-20 mcg/kg body weight patients should be additionally injected with galanthamine intramuscularly once daily for 7-10 d at the dosage 5 mg, moreover, decreasing the number of estradiol injections up to once/3 d. The innovation suggested provides high antiamnestic effect at decreased dosage of preparations due to their agonistic action.
EFFECT: higher efficiency of therapy.
FIELD: medicine, gerontology.
SUBSTANCE: the present innovation deals with rehabilitation therapy of cerebrovascular diseases. One should introduce microcirculators and nootropic preparations to conduct training neuropsychological procedures. Moreover, microcirculatory and nootropic preparations should be introduced as intravenous infusions for 10 d, ten during 1 mo it is necessary to introduce tableted forms of the same preparations at simultaneous neuropsychological training directed to improving household skills valuable for a patient that deal with memorizing different names, important dates, names of medicinal preparations and location of domestic articles. On achieving a success the tasks should be complicated. Training should last for 30 min carried out thrice weekly: therapy course includes 12 trainings. The innovation widens the number of preparations for treating elderly and senile patients at discirculatory encephalopathy stage III and coarse cognitive deficiency.
EFFECT: higher efficiency of therapy.
3 ex, 1 tbl
FIELD: medicine, pharmacology.
SUBSTANCE: claimed agent represents N-isopropylamide-2-(1-phenylethyl)-aminoethanesulfonic acids and is useful in treatment of various brain and spinal cord lesions.
EFFECT: new neuroprotector having no toxic effect.
6 dwg, 7 tbl, 5 ex
FIELD: organic chemistry, medicine, pharmacology, pharmacy.
SUBSTANCE: invention relates to a new physiologically active composition effecting on nicotine receptors and prepared in the form of tablets, granules, capsules, suspensions, solutions and injections. As an active component the composition comprises pharmaceutically effective amount of substituted 1-oxo-1,2-dihydro[2,7]-naphthyridine of the general formula (1)
or its salt, N-oxide or hydrate wherein R1 represents hydrogen atom, inert substitute, optionally substituted (C1-C5)-alkyl, optionally substituted amino-group; R2 and R3 represent independently of one another hydrogen atom, nitrile group, formyl group, inert substitute, optionally substituted (C1-C5)-alkyl, carboxyl group, optionally substituted (C1-C6)-alkyloxycarbonyl group or optionally substituted carbamoyl group; R4 at carbon atoms of pyridine moiety represents: hydrogen atom, halogen atom, inert substitute, optionally substituted hydroxy-(C1-C5)-alkyl, optionally substituted amino-group, optionally substituted hydroxyl group, optionally substituted (C1-C6)-alkyloxycarbonyl group, optionally substituted carbamoyl group; R4 at nitrogen atom of pyridine moiety forms pyridinium salt with pharmacologically acceptable anion and represents inert substitute. Also, invention relates to new substituted 1-oxo-1,2-dihydro[2,7]naphthyridines of the general formula (1) or their salts, N-oxides or hydrates wherein R1 and R4 have value given in cl. 1, and R2 and R3 represent independently of one another carboxyl group, optionally substituted (C1-C6)-alkyloxycarbonyl group or optionally substituted carbamoyl group. Also, invention relates to a method for their preparing and to a method for modulating activity of nicotine receptor and using compounds of the general formula (1) by cl. 1 for preparing physiologically active composition, and as ligands of nicotine receptors for aims of experimental investigations of physiological processes as "pharmacological tools". Also, invention relates to a set for preparing the composition.
EFFECT: improved preparing method, valuable properties of compounds and compositions.
7 cl, 2 sch, 2 tbl, 5 ex
FIELD: organic chemistry, medicine, pharmacology.
SUBSTANCE: invention relates to an agent representing 2-allylthiobenzimidazole hydrochloride of the formula:
Proposed agent is used for stimulation of teaching process, recovery of memory and emotional status. Invention can be used in experimental pharmacology and medicine also. Invention provides preparing a new agent based on derivatives of benzimidazole representing the most perspective agent among potential stimulators of mental and physical working ability.
EFFECT: valuable properties of agent.
2 dwg, 16 tbl, 1 ex
FIELD: medicine, pharmacy.
SUBSTANCE: invention represents a pharmaceutical tablet comprising a core and bound envelope wherein (a) core comprises solid particles of water-soluble dye dispersed in matrix, and (b) envelope comprises hellanic gum. Due to the presence of water-soluble dye in the tablet core it shows spotted shape that provides easy recognition of the tablet. The tablet is useful for peroral and intraoral administration.
EFFECT: improved and valuable properties of tablet.
30 cl, 6 ex