Method for preparing pharmaceutical microcapsules of cephalosporins
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to pharmaceutical microcapsulation of cephalosporins related to β-lactam antibiotics. As a microcapsule shell, the method of pharmaceutical microcapsulation of cephalosporins uses konjac gum; the microcapsules are prepared by physical-chemical technology implying the precipitation in a non-solvent using two precipitants - carbinol and diethyl ester in ratio 1:3; the method is conducted at 25°C with no special equipment.
EFFECT: invention provides simplified and accelerated preparation of the water-soluble pharmaceutical microcapsules of cephalosporins in konjac gum, loss reduction in preparing the microcapsules (higher yield-mass).
The invention relates to the field of microencapsulation of drugs of cephalosporin group related to β-lactam antibiotics, in Konakovo gum physico-chemical method for the deposition aristotelem.
Previously known methods for producing microcapsules of drugs. Thus, in U.S. Pat. 2092155 IPC A61K 047/02, A61K 009/16 published 10.10.1997 Russian Federation proposed a method for microencapsulation of drugs, based on the use of special equipment use of irradiation with ultraviolet rays.
The disadvantages of this method are the duration of the process and the use of ultraviolet radiation, which can influence the formation of microcapsules.
In Pat. 2101010 IPC A61K 9/52, A61K 9/50, A61K 9/22, A61K 9/20, A61K 31/19 Russian Federation published 10.01.1998 proposed chewable form of the drug with taste masking, having the properties of a controlled release drug product that contains microcapsules with a size of 100-800 microns in diameter and consists of pharmaceutical kernel crystalline ibuprofen and polymeric coating comprising a plasticizer, elastic enough to resist chewing. The polymer coating is a copolymer based on methacrylic acid.
The drawbacks of the invention: the use of a copolymer based on methacrylic acid, as these polymer coatings can cause cancer; complexity; the duration of the process.
In the article "Razrabotka microencapsulated and gel products and materials for various industries", Russian chemical journal, 2001, .XLV, No. 5-6, s-135 is described a method of producing microcapsules of drugs by the method of gas-phase polymerization, since the authors considered unsuitable method of chemical koatservatsii from aqueous media for microencapsulation of drugs due to the fact that most of them are water-soluble. The process of microencapsulation by the method of gas-phase polymerization using n-xylylene includes the following basic stages: evaporation dimer n-xylylene (170°C), thermal decomposition of it into the pyrolysis furnace (650°C at a residual pressure of 0.5 mm Hg), the transfer of the reaction products in the "cold" chamber of polymerization (20°C, the residual pressure of 0.1 mm Hg), deposition and polymerization on the surface of the protected object. Luggage polymerization is performed in the form of a rotating drum, the optimal speed for powder coating 30 rpm, the Thickness of the shell is governed by the time of coating. This method is suitable for the encapsulation of any solids (except prone to intense sublimation). Produces the text of poly-n-xylylene vysokokritichnyh polymer, with high orientation and dense packing, provides a conformal coating.
Disadvantages of the proposed method are the complexity and duration of the process, using the method of gas-phase polymerization, which makes the method inapplicable to obtain microcapsules of drugs in polymers protein nature due to the denaturation of proteins at high temperatures.
In Pat. WO/2011/127030 US IPC A61K 8/11; B01J 2/00; B01J 13/06; C11D 3/37; C11D 3/39; C11D 17/00 published on 13.10.2011 proposed several methods for producing microcapsules: interfacial polymerization, thermoanaerobium separation of the phases, spray drying, evaporation of the solvent and other
The disadvantages of the proposed methods is the complexity, duration processes, as well as the use of special equipment (filter (Albet, Dassel, Germany), spray dryer for collecting particles (Spray-4M8 Dryer from ProCepT, Belgium)).
In Pat. WO/2011/104526 GB IPC B01J 13/00; B01J 13/14; C09B 67/00; C09D 11/02 published on 01.09.2011 method for obtaining a dispersion of encapsulated solid particles in a liquid medium, comprising: a) grinding compositions, including solid, liquid medium and a polyurethane dispersant with an acid number of from 0.55 to 3.5 mmol per gram of dispersant, the composition comprises from 5 to 40 parts of the polyurethane dispersant to 100 parts of the solid products in the su; and b) crosslinking the polyurethane dispersant in the presence of solid and liquid medium, so as to encapsulate the solid particles, which polyurethane dispersant contains less than 10% by weight of the recurring elements of polymeric alcohols.
Disadvantages of the proposed method are the complexity and duration of the process of production of microcapsules, and that the encapsulated particles of the proposed method are useful as colorants in inks, especially ink jet printing for the pharmaceutical industry this technique is not applicable.
The closest method is the method proposed in U.S. Pat. 2134967 IPC A01N 53/00, A01N 25/28 published 27.08.1999 Russian Federation (1999). Water is dispersed solution of a mixture of natural lipids and a PYRETHROID insecticide in the weight ratio of 2-4:1 in an organic solvent, which leads to simplification of the method of microencapsulation.
The disadvantage of this method is the dispersion in the aquatic environment, which makes the proposed method applicable to the production of microcapsules of water-soluble drugs in water-soluble polymers.
The technical objective is the simplification and acceleration of the process of obtaining the microcapsules vodorastvorimyh drugs group of cephalosporins in Konakovo gums, reducing losses upon receipt of the microcapsules (increase in mass).
Re the giving of the technical problem is achieved by a method of producing microcapsules drugs group of cephalosporins, related to β-lactam antibiotics, characterized in that as the shell of the microcapsules is Konakova gum, obtaining microcapsules is carried out by physical and chemical deposition method by nerastvorim using two precipitators - carbinol and diethyl ether, the retrieval process is carried out without special equipment.
A distinctive feature of the proposed method is the use as the shell of the microcapsules drug group cephalosporins related to β-lactam antibiotics, Konakovo gums, and obtaining microcapsules physico-chemical deposition method by nerastvorim using two precipitators - carbinol and diethyl ether.
The result of the proposed method are obtaining microcapsules drug group cephalosporins related to β-lactam antibiotics in Konakovo gum at 25°C for 15 minutes. The output of the microcapsules is over 90%.
Required for microencapsulation of Konakova gum was industrial production under the trade name konjac cercon and konjac gum 3600.
EXAMPLE 1. Obtaining microcapsules Ceftriaxone in the konjak cerocon using carbinol and diethyl ether as the precipitating, the ratio of 1:3
To 6 g of 5% solution of konjac cerocon in diethyl who Fira add 0.01 g of the drug Is (ester of glycerol with one or two molecules of citric acid, and citric acid, as Tihonova may be etherification other glycerides and as hydroxy acid other fatty acids. Free acid groups can be neutralized with sodium as surfactants. The resulting mixture was put on a magnetic stirrer and include mixing. 0.1 g of Ceftriaxone powder dissolved in 0.5 ml of water and transferred into a solution of konjac cerocon in diethyl ether. After the formation of the Ceftriaxone independent solid phase very slowly added dropwise 5 ml of carbinol and 1 ml of distilled water. The resulting suspension of microcapsules is filtered by the filter SCHOTT 16 class then washed with acetone, dried in a desiccator over calcium chloride.
Obtained 0.35 g of a white powder. The yield was 88%.
EXAMPLE 2. Obtaining microcapsules Cefotaxime in konjak cerocon using carbinol and diethyl ether as the precipitating, the ratio of 1:3
To 6 g of 5% solution of konjac cerocon in diethyl ether is added 0.01 g of the drug Is as surfactants. The resulting mixture was put on a magnetic stirrer and include mixing. 0.1 g of the powder Cefotaxime dissolved in 0.5 ml of water and transferred into a solution of konjac cerocon in diethyl ether. After the formation of the Cefotaxime independent solid phase very slowly added dropwise 5 ml of CT is inola and 1 ml of distilled water. The resulting suspension of microcapsules is filtered by the filter SCHOTT 16 class then washed with acetone, dried in a desiccator over calcium chloride.
Received 0.39 g of white powder. The yield was 98%.
EXAMPLE 3. Obtaining microcapsules is anticipated in the konjak cerocon using carbinol and diethyl ether as the precipitating, the ratio of 1:3
To 6 g of 5% solution of konjac cerocon in diethyl ether is added 0.01 g of the drug Is as surfactants. The resulting mixture was put on a magnetic stirrer and include mixing. 0.1 g of Cefazolin powder dissolved in 0.5 ml of water and transferred into a solution of konjac cerocon in diethyl ether. After the formation of the anticipated independent solid phase very slowly added dropwise 5 ml of carbinol and 1 ml of distilled water. The resulting suspension of microcapsules is filtered by the filter SCHOTT 16 class then washed with acetone, dried in a desiccator over calcium chloride.
Obtained 0.34 g of a white powder. The yield was 89%.
The obtained microcapsules drug group cephalosporins related to β-lactam antibiotics, in Konakovo gum physico-chemical method for the deposition nerastvorim using carbinol and diethyl ether as precipitators. The process is simple to perform and lasts for 15 minutes, does not require special the real hardware.
Konakova gum is widely used in the pharmaceutical industry drugs for weight loss and regulation chair, as a binder in tablets. In the Russian Federation is permitted in food products according to TI in an amount up to 10 g/kg of product (p SanPiN 22.214.171.1243-03). Technological function: thickener, geleobrazovanie, stabilizer, means for tableting. Composition: neutral polysaccharide glucomannan consists of D-glucose and D-mannose in a ratio of from 1:4 to 2:3. Receive: a three-year, weighing more than a kilogram of root tubers of Amorphophallus plants are cut, dried, milled and sieved flour is subjected to swelling in water, treated with lime milk and filtered. Glucomannan is precipitated from the filtrate with alcohol and dried.
The proposed method is suitable for the pharmaceutical industry due to the minimal loss of speed, ease of acquisition and allocation of microcapsules cephalosporins related to β-lactam antibiotics, in Konakovo gums.
The method of producing microcapsules drugs group of cephalosporins in Konakovo gum in diethyl ether, characterized in that as the shell of the microcapsules is Konakova gum, obtaining microcapsules is carried out by physical and chemical deposition method by nerastvorim using two precipitator is - carbinol and diethyl ether, taken in the ratio 1:3, the retrieval process is carried out at 25°C without special equipment.
SUBSTANCE: claimed invention relates to medicine and describes method of obtaining delivering particles of fragrance, containing core material and envelope, said envelope at least partially surrounds said core material and at least 75% of said delivering particles of fragrance are characterised by tensile strength from approximately 0.2 MPa to approximately 10 MPa, with particle size from approximately 1 micron to approximately 80 micron and thickness of particle walls from approximately 60 nm to approximately 250 nm; and said delivering particles of fragrance are characterised by release of fragrance from 0% to approximately 30%. In addition to creation of possibility to reduce number of agent which produces favourable impact, such particles make it possible to extend spectrum of applied agents which produce favourable impact.
EFFECT: in cases of application in compositions, for instance, detergents, or compositions for fabric care, such particles increase efficiency of delivery of agent which produces favourable impact, making it possible to use reduced amounts of agents which produce favourable impact.
11 cl, 9 tbl, 13 ex
SUBSTANCE: invention relates to a powder coating composition obtained from aqueous dispersion containing polymer-encapsulated particles, said particles including particles encapsulated in a brittle polymer which can easily break up under ambient conditions. The invention also discloses a method of preparing an aqueous dispersion of particles encapsulated in a brittle polymer, a base which is at least partially coated with a coating deposited from said composition, a multilayer composite coating, a method of preparing a powder coating composition, a method of preparing an aqueous dispersion of particles encapsulated in a brittle polymer and a powder coating composition formed from said dispersion prepared using said method, as well as a reflecting surface which is at least partially coated with a layer which gives the colour of an uncovered coating deposited from disclosed powder coating compositions.
EFFECT: obtaining aqueous dispersion of particles encapsulated in a brittle polymer in which repeated agglomeration of particles is minimised and which enables to obtain a powder coating composition which contains multiple polymer-encapsulated particles having maximum turbidity so that the coating has absorption or reflection in the visible spectrum which is close to that of the given coating.
22 cl, 14 ex, 1 tbl
FIELD: process engineering.
SUBSTANCE: invention relates to production of minor spherical particles of active agent in sole liquid phase solution. Sole liquid phase comprises active agent, agent facilitating phase separation and first thinner. Phase separation is induced at controller rate in solution to cause separation active agent into "fluid-solid" and to form liquid and solid phases. Note here that inducing comprises solution cooling. Solid phase contains minor spherical particles of active agent. Liquid phase comprises agent facilitating phase separation and thinner. Minor spherical particles feature particle size varying from 0.01 mcm to about 200 mcm.
EFFECT: minor spherical particles of active agent in sole liquid phase solution.
77 cl, 49 dwg, 4 tbl, 36 ex
FIELD: process engineering.
SUBSTANCE: invention maybe used for efficient fire extinguishing, fast cooling of overheated structures and production of lower-flammability compounds. Microcapsules have a micro-sphere-like core containing water or water solution in gel state, main shell around said core to provide for core stable shape and composition and rule out water evaporation therefrom the core, and, additionally, comprises outer shell with lyophilic properties. Versions of proposed methods comprises producing aforesaid core via interaction of appropriate initial water solutions to be placed in microsphere and containing appropriate components of the shell with components of solutions to be precipitated and used for producing and cross-linking of gel, and producing additional lyophilic shell via interaction of components of initial solutions with appropriate components in organic medium.
EFFECT: high efficiency in fire extinguishing or fast cooling of overheated structures.
21 cl, 1 tbl, 10 ex
SUBSTANCE: invention relates to use of polymer material, and specificaly to use of particulate polymer material as an active agent carrier. The polymer material is a polymer obtained from copolymerisation of pyrrole with quadratic or croconic acid or its derivative.
EFFECT: use in accordance with the invention enables to use polymer material as a composition in form of particles as an absorbent or prolonged release agent.
16 cl, 8 dwg, 1 tbl, 10 ex
SUBSTANCE: invention relates to a solid re-dispersible emulsion which is a direct emulsion of fabric softener encapsulated in a polysaccharide shell which is stabilised by ions of polyvalent metals selected from Ca2+, Sr2+, Ba2+, Al3+, Cu2+, Zn2+, where the shell is initially insoluble in water but becomes soluble in water through ion donation. The polysaccharide is biodegradable and is selected from a group comprising alginates and carrageenans. Similar solid re-dispersible emulsions are primarily used in agents for washing or taking care of clothes. Powdered fabric softeners are easy to store, apportion and, if necessary, combine with powdered detergents during production.
EFFECT: invention enables production of fabric softeners previously produced as liquid compositions in solid powdered form.
14 cl, 2 ex
SUBSTANCE: invention relates to capsular additives for rubber, obtained in form of microcapsules with a polymer wall and a nucleus, which contains at least one additive for rubber. The capsule wall is formed by at least one component from a reactive resin and at least one component from a polyelectrolyte or ionomer component. The reactive resin is melamine formaldehyde resin and/or polyurea resin. The invention also relates to a method of preparing such microcapsules. The proposed microcapsules are used for vulcanising natural and synthetic rubber. The microcapsules are thermally and mechanically stable in conditions for preparing and processing rubber compositions in kneading machines, manglers or twin-screw extruders at temperatures ranging from 120°C to 140°C.
EFFECT: microcapsular additives are uniformly distributed in rubber mixture and prevent formation of a heterogeneous rubber/additive system.
30 cl, 12 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: microcapsules, in which water droplet or droplets including the dissolved active ingredient are incapsulated in the hardened hydrophobic cover-matrix, are described. Also the methods of obtaining of the specified microcapsules and their application are described.
EFFECT: development of microcapsules which possess the improved stability and provide the adjustable and-or prolonged release of an active ingredient.
40 cl, 8 dwg, 4 tbl, 8 ex
FIELD: medicine; pharmacology.
SUBSTANCE: carrying out of treatment of disease, in particular, diabetes, by implantation of the encapsulated devices containing a covering and cells, thus density of cells makes 100000 cells/ml, and the covering contains acrylate polyethylene alcohol (PEG) high density with molecular mass from 900 to 3000 Dalton, and also a sulfonated comonomer.
EFFECT: minimisation of the tissue response, augmentation of concentration of cells and augmentation of time of viability of cells in the specified devices.
83 cl, 33 dwg, 8 tbl, 20 ex
SUBSTANCE: composition is used for making hollow micro-spheres, which are used as a component of boring solutions when finding and producing oil, as low density filler in various composite materials, used in machine building, aviation and ship building, space technology, and when making heat insulation materials. The composition contains the following, in the given mass ratios: resol phenol-formaldehyde resin with relative viscosity of 5000-9000 cP - 100, porofor (5), polyether based on ethylene oxide copolymer and propylene oxide with molecular mass of 4000-6000 (2-3).
EFFECT: higher space factor of the boring solution micro-spheres, improved looseness of the micro-spheres, increased strength during hydrostatic compression.
1 tbl, 3 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: declared group of inventions refers to a pharmacological composition for intranasal introduction for cerebral delivery, and a method for preparing said composition. The declared composition comprises a container base formed by porous particles of calcium carbonate and titanium dioxide of particle size 100-5000 nm and a pharmacologically active component - loperamide. The container surface is modified by surfactants specified in polysorbates, or by polymers specified in a group containing glycosaminoglycanes and polypeptides, or their combination. A method for preparing the pharmacological composition consists in preparing the container base by porous particle synthesis, sorption of loperamide in its pore spaces and modification of the container surface by polymers and surfactants by container incubation in their solutions.
EFFECT: invention provides preparing the pharmacological composition which is applicable for cerebral loperamide delivery after the intranasal introduction.
5 cl, 5 dwg, 1 ex
SUBSTANCE: invention relates to composition for peroral introduction, which possesses properties of modified release. According to invention composition includes pharmaceutically acceptable excipients and complex medication-ion-exchanging resin with coating with modified release, which contains pharmaceutically active medication, combined with pharmaceutically acceptable ion-exchanging resin. Complex has solidified barrier coating with high rupture strength, water-permeable, water-insoluble, which contains polyvinyl acetate polymer, stabiliser and efficient amount of plastifier. Said coating is in fact non-sticky, when applied onto complex in absence of anti-adhesive preparation, if composition presents tablet, complex medication-ion-exchanging resin with coating additionally contains release-retarding substance in matrix together with complex medication-ion-exchanging resin. Invention also relates to product with modified release, including package which contains composition described above.
EFFECT: invention ensures regulated prolonged active agent release without breaking coating integrity, without application of water-soluble impregnating substances and without agglomeration of complex particles during application of coating.
27 cl, 22 ex
SUBSTANCE: there are described oral dosage forms of risedronate containing safe and effective amount of a pharmaceutical composition containing risedronate, a chelating agent and an agent for effective delayed release of risedronate and the chelating agent in small intestine. The pharmaceutical composition is directly released in a small intestine of a mammal with ensuring pharmaceutically effective absorption of bisphosphonate together with or without food or drinks. Present invention essentially reduces interaction between risedronate and food or drinks which leads to that the active component of bisphosphonate becomes inaccessible to absorption. Thus, the final oral dosage form can be taken with and without food. Further, present invention covers delivery of risedronate and the chelating agent in a small intestine, essentially reducing irritation of upper gastrointestinal tract associated with bisphosphonate therapy. These advantages simplify previous, complicated regimens and can lead to more complete observance of the bisphosphonate therapy regimen.
EFFECT: present invention essentially reduces interaction between risedronate and food or drinks which leads to that the active component of bisphosphonate becomes inaccessible to absorption.
23 cl, 12 ex
SUBSTANCE: invention refers to a carrier for drugs, biologically active substances, biological objects used in medicine for diagnostics and treatment in pharmaceutical industry. The carrier represents a material sensitive to external magnetic or electric fields and consisting of magnetic or ferroelectric material filmed with biocompatible thermosensitive, biodegradable polymer and/or dispersed in thermosensitive medium properties of which change with varying temperature relative to that of human body within 15.9 to 42°C. The magnetic or ferroelectric materials are made of substance with great magnetocaloric or electrocaloric component effect 1 to 13 K, have temperature of magnetic or ferroelectric phase transition within temperature range 33 to 37°C, and are chosen from the group including rare-earth, transition and precious metals, their alloys and compounds.
EFFECT: invention also concerns methods of controlled drug delivery by means of such carrier with enabling release thereof (regulated desorption) in the preset point.
32 cl, 9 ex
FIELD: medicine; pharmacology.
SUBSTANCE: minitablets have a kernel and an external cover which makes 2-15% of gross weight of minitablets, the kernel of the specified minitablets, includes a venlafaxine hydrochloride, microcrystallic cellulose and a polyvinylpyrolidone, and the specified cover includes polymer, insoluble in water, and a polymer, soluble in water.
EFFECT: provision of levels of concentration in a blood plasma above the minimum therapeutic concentration during the long period of time.
10 cl, 1 dwg, 1 tbl, 5 ex
SUBSTANCE: invention discovers improved composition for profile control of active compound release through the digestive tract, including particles, especially granules, containing the active compounds. They are covered with coating material, solution of which depends on pH value, or polymethacrylate material, solution of which, for preference, depends on pH value, the definite thickness, desirable place and speed of the active compound release. In preferable compositions two or more particles, in which particles of each multitude are covered with the coating material, the solution which depends on pH value, or polymethacrylate material, of different thickness in comparison with the particles of each other multitude, are contained in capsules with enterosoluble coating and provide the active substance release in different desirable places of the digestive tract.
EFFECT: provision of active substance release in desirable places of digestive tract.
28 cl, 7 dwg, 9 ex
FIELD: medicine, pharmacy.
SUBSTANCE: invention relates to sustained-release medicinal formulation composition comprising venlafaxin hydrochloride as an active component. In this formulation venlafaxin hydrochloride in common with a binding agent is applied on inert core as lozenge form (nonpareil) followed applying with a cover-insulating polymeric layer for providing stability and additional cover with external polymeric layer providing the sustained-release of venlafaxin hydrochloride.
EFFECT: improved and valuable properties of composition.
18 cl, 1 tbl, 4 ex
SUBSTANCE: the [present innovation deals with manufacturing intestinally soluble capsular forms of medicinal preparations, particularly, to the technology for creating capsular membranes of improved protective properties. The innovation deals with the method for obtaining capsular membrane out of calcium alginate due to successive keeping capsular nuclei in solutions of sodium alginate and calcium chloride, in which sodium alginate solution at concentration of 1.5-2.0% (weight/volume) should be pre-treated with ultrasound for about 8-10 at the power of 400-450 W/sq. cm. Calcium chloride solution should be applied at concentration of 2.0-2.5%, moreover, the terms for keeping capsular nuclei in solutions of sodium alginate and calcium chloride corresponds to 5 min in every solution.
EFFECT: higher efficiency.
1 dwg, 3 ex, 1 tbl
FIELD: medicine, pharmaceutics.
SUBSTANCE: claimed invention relates to field of pharmacology and clinical medicine and describes pharmaceutical compositions of 2-amino-2-[2-(4-octylphenyl)ethyl]propan-1,3-diole in free form and/or in form of pharmaceutically acceptable salt, where as auxiliary substances they contain lactose, starch and/or starch derivatives, selected from acetylated starch, sodium salt of starch carboxymethyl ether, pregelatinised starch, sodium starch glycolate, gelatin, binding agent, and lubricant with specified ratio.
EFFECT: invention makes it possible to extend possibility for cheaper in industrial manufacturing preparation for treatment of disseminated sclerosis.
7 cl, 16 ex