Method for preparing cephalosporin microcapsules in interferon

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a method for preparing interferon-coated cephalosporin microcapsules. The declared method is characterized by mixing 1% aqueous solution of human leukocyte α- or β-interferon, cephalosporin powder and preparation E472c as a surfactant. The prepared mixture is stirred until the reaction components are fully dissolved, and after a transparent solution is generated, methanol 1 ml as a first non-solvent and then isopropyl alcohol 5 ml as a second non-solvent are slowly added drop-by-drop, then filtered, washed in acetone and dried.

EFFECT: invention provides preparing the high-yield cephalosporin microcapsules and ensuring the loss reduction.

8 ex

 

The invention relates to the field of microencapsulation of drugs of cephalosporin group related to β-lactam antibiotics, α - and β-forms of human leukocyte interferon.

Previously known methods for producing microcapsules of drugs. Thus, in U.S. Pat. 2092155 IPC A61K 047/02, AK 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. 2095055 IPC AC 9/52, AK 9/16, AC 9/10 of the Russian Federation published 10.11.1997 method for obtaining a solid non-porous microspheres includes melting pharmaceutically inactive substance carrier, the dispersion of a pharmaceutically active substance in the melt in an inert atmosphere, spraying the resulting dispersion in the form of a mist in the freezing chamber under pressure in an inert atmosphere at a temperature of from -15 to -50°C, and the separation of the obtained microspheres into fractions by size. The suspension is intended for administration by parenteral injection, contains an effective amount specified is trosper, distributed in a pharmaceutically acceptable liquid vector, and the pharmaceutically active substance is insoluble microspheres in a specified liquid medium.

Disadvantages of the proposed method: the complexity and duration of the process, the use of special equipment.

In Pat. 2091071 IPC AC 35/10 Russian Federation published 27.09.1997 method for obtaining the drug by dispersion in a ball mill to obtain microcapsules.

The disadvantage of this method is the use of a ball mill, which can lead to the destruction of part of microcapsules and eventually to a decrease in the yield of the final product.

In Pat. 2076765 IPC B01D 9/02 Russian Federation published 10.04.1997 method for obtaining dispersed particles of soluble compounds in the microcapsules by crystallization from a solution, wherein the solution is dispersed in an inert matrix, cooled and, by changing the temperature, get dispersed particles.

The disadvantage of this method is the difficulty of execution: obtaining microcapsules by dispersion with subsequent change of temperatures, which slows down the process.

In Pat. 2101010 IPC AC 9/52, AK 9/50, AK 9/22, AK 9/20, AK 31/19 Russian Federation published 10.01.1998 proposed chewable form of the drug with taste masking with properties controlled what about the release of a medicinal product, contains micro-capsules of the 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: use of a copolymer based on methacrylic acid, as these polymer coatings can cause cancer; obtaining microcapsules by the method of suspension polymerization; complexity; the duration of the process.

In Pat. 2139046 IPC AC 9/50, AK 49/00, AK 51/00 Russian Federation published 10.10.1999 method for obtaining microcapsules as follows. Emulsion oil-in-water prepared from organic solution containing dissolved mono-, di-, triglyceride, preferably of tripalmitin or tristearin, and possibly therapeutically active substance, and an aqueous solution containing a surfactant, it is possible to evaporate part of the solvent, add redispersible agent and the mixture is subjected to drying by freezing. After freezing the mixture is then dispersed in an aqueous medium to separate the particles from organic substances and a hemispherical or spherical microcapsules dried.

Nedostatkami proposed the military method are the complexity and duration of the process, the use of drying by freezing, which takes time and slows down the process of production of microcapsules.

In Pat. 2159037 IPC A01N 25/28, A01N 25/30 Russian Federation published 20.11.2000 method for obtaining microcapsules polymerization reaction at the phase boundary, containing solid agrochemical material 0.1 to 55 wt.%, suspended in peremestivsheesya water organic liquid, from 0.01 to 10 wt. % non-ionic dispersant, active on the phase boundary and is not acting as an emulsifier.

Disadvantages of the proposed method: the complexity, duration, using wysokosciowe mixer, obtaining microcapsules by chemical polymerization, technological complexity.

In Pat. 2173140 IPC AC 009/50, AK 009/127 Russian Federation published 10.09.2001 method for obtaining kremnijorganicheskih microcapsules using a rotary cavitation plants with high shear effort and powerful acoustic phenomena of sound and ultrasound range for dispersion.

Disadvantages of the proposed method: the complexity, duration, using wysokosciowe mixer.

In Pat. 2359662 IPC AC 009/56, A61J 003/07, B01J 013/02, A23L 001/00 published 27.06.2009 Russian Federation proposed a method of producing microcapsules using spray cooling in races is ylitalo the tower Niro under the following conditions: air temperature 10°C, the air temperature at the outlet 28°C, the speed of rotation of the spray drum 10000 rpm/min Microcapsules according to the invention have improved stability and provide adjustable and/or prolonged release of the active ingredient.

Disadvantages of the proposed method are the duration of the process and the use of special equipment, a set of conditions (temperature of inlet air 10°C, the temperature at the outlet 28°C, the speed of rotation of the spray drum 10000 rpm).

In Pat. 20110223314 IPC B05D 7/00 20060101 B05D 007/00, VS 3/02 20060101 VS 003/02; VS 11/00 20060101 VS 011/00; B05D 1/18 20060101 B05D 001/18; B05D 3/02 20060101 B05D 003/02; B05D 3/06 20060101 B05D 003/06 from 10.03. 2011 U S describes a method of producing microcapsules by the method of suspension polymerization, belonging to the group of chemical methods with the use of the new device and ultraviolet radiation.

The disadvantage of this method is the complexity and duration of the process, the use of special equipment, the use of ultraviolet radiation.

In Pat. WO/2011/150138 US IPC C11D 3/37; B01J 13/08; C11D 17/00 published on 01.12.2011 describes a method for solid particles, water-soluble agents polymerization method.

The disadvantages of this method are the complexity and duration of the process.

In Pat. WO/2011/127030 US IPC AC 8/11; B01J 2/00; B01J 13/06; C11D 3/37; C11D 3/39; 11D 17/00 published on 13.10.2011 proposed several methods for producing microcapsules: interfacial polymerization, thermointelligence 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-M Dryer from ProCepT, Belgium)).

In Pat. WO/2011/104526 GB IPC B01J 13/00; B01J 13/14; SV 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 per 100 parts of solid product, by weight; 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 ink, paying ink jet printing for the pharmaceutical industry this technique is not applicable.

ITAT. WO/2011/056935 US IPC C11D 17/00; A61K 8/11; B01J 13/02; C11D 3/50 published on 12.05.2011 described a method of producing microcapsules with a size of 15 microns. As the shell material proposed polymers of the group consisting of polyethylene, polyamides, polystyrene, polyisoprenes, polycarbonates, polyesters, polyacrylates, polyureas, polyurethanes, polyolefins, polysaccharides, epoxy resins, vinyl polymers and mixtures thereof. The proposed polymer membranes are sufficiently impervious core material and materials in the environment in which the encapsulated benefit agent will be used to provide benefits that will be received. The core of the encapsulated agents may include perfume, silicone oils, waxes, hydrocarbons, higher fatty acids, essential oils, lipids, cooling the skin fluids, vitamins, sunscreens, antioxidants, glycerin, catalysts, bleach particles, particles of silicon dioxide and other

Disadvantages of the proposed method are the complexity, the length of the process, using as the shells of the microcapsules polymers of synthetic origin, and mixtures thereof.

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 Pietr odnogo 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 production of microcapsules of water-soluble drugs of cephalosporin group in α - and β-forms of human interferon leikocitarnom, reducing losses upon receipt of the microcapsules (increase in mass).

The solution of the technical problem is achieved by a method of producing microcapsules drug group cephalosporins related to β-lactam antibiotics (I-IV), characterized in that as the shell of the microcapsules is human leukocyte interferon in α - and β-forms upon receipt of the microcapsules physico-chemical deposition method by nerastvorim using two precipitators, methanol and isopropyl alcohol, 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 drugs group of cephalosporins, related to β-lactam antibiotics of human leukocyte interferon in α - and β-forms when they receive the research Institute of physico-chemical method for the deposition nerastvorim using isopropyl alcohol and methanol as precipitators.

The result of the proposed method are obtaining microcapsules drug group cephalosporins related to β-lactam antibiotics in α - and β-Tomah of human leukocyte interferon at 25°C for 15 minutes. The output of the microcapsules is over 90%.

EXAMPLE 1. Obtaining microcapsules Cefotaxime in human leukocyte interferon (β-IFN)using methanol and isopropyl alcohol as a precipitating, the ratio of 3:1

To 2.5 g of 1% aqueous solution of human leukocyte interferon (β-IFN) add 0.075 g of powder Cefotaxime and 0.05 g of the drug A with as surfactants. The resulting mixture was put on a magnetic stirrer and include mixing. After the dissolution of the components of the reaction mixture until a clear solution is formed very slowly poured dropwise 1 ml of methanol as the first precipitator, and then 5 ml of isopropyl alcohol as the second. 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 0,095 g of white powder. The yield was 95%.

EXAMPLE 2. Obtaining microcapsules Cefotaxime in human leukocyte interferon (α-IFN) using methanol and isopropyl alcohol is as precipitators, the ratio of 3:1

To 2 g of 1% aqueous solution of human leukocyte interferon (α-IFN) add to 0.060 g of powder Cefotaxime and 0.05 g of the drug A with as surfactants. The resulting mixture was put on a magnetic stirrer and include mixing. After the dissolution of the components of the reaction mixture until a clear solution is formed very slowly poured dropwise 1 ml of methanol as the first precipitator, and then 5 ml of isopropyl alcohol as the second. 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 0.07 g of white powder. The yield was 86%.

EXAMPLE 3. Obtaining microcapsules Ceftriaxone in human leukocyte interferon (β-IFN) using methanol and isopropyl alcohol as a precipitating, the ratio of 3:1

To 2.5 g of 1% aqueous solution of human leukocyte interferon (β-IFN) add 0.075 g of Ceftriaxone powder and 0.05 g of the drug A with as surfactants. The resulting mixture was put on a magnetic stirrer and include mixing. After the dissolution of the components of the reaction mixture until a clear solution is formed very slowly poured dropwise 1 ml of methanol as the first sieges the body, and then 5 ml of isopropyl alcohol as the second. 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 0,097 g of white powder. The yield was 97%.

TAKE 4. Obtaining microcapsules Ceftriaxone in human leukocyte interferon (α-IFN) using methanol and isopropyl alcohol as a precipitating, the ratio of 3:1

To 2 g of 1% aqueous solution of human leukocyte interferon (α-IFN) add to 0.060 g of Ceftriaxone powder and 0.05 g of the drug A with as surfactants. The resulting mixture was put on a magnetic stirrer and include mixing. After the dissolution of the components of the reaction mixture until a clear solution is formed very slowly poured dropwise 1 ml of methanol as the first precipitator, and then 5 ml of isopropyl alcohol as the second. 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 0.07 g of white powder. The yield was 88%.

EXAMPLE 5. Obtaining microcapsules is anticipated in the human leukocyte interferon (β-IFN) using methanol and isopropyl alcohol as a precipitating, soo is wearing a 3:1

To 2.5 g of 1% aqueous solution of human leukocyte interferon (β-IFN) add 0.075 g of Cefazolin powder and 0.05 g of the drug A with as surfactants. The resulting mixture was put on a magnetic stirrer and include mixing. After the dissolution of the components of the reaction mixture until a clear solution is formed very slowly poured dropwise 1 ml metanoia as the first precipitator, and then 5 ml of isopropyl alcohol as the second. 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 0,089 g of white powder. The yield was 89%.

EXAMPLE 6. Obtaining microcapsules is anticipated in the human leukocyte interferon (α-IFN) using methanol and isopropyl alcohol as a precipitating, the ratio of 3:1

To 2 g of 1% aqueous solution of human leukocyte interferon (α-IFN) add to 0.060 g of Cefazolin powder and 0.05 g of the drug A with as surfactants. The resulting mixture was put on a magnetic stirrer and include mixing. After the dissolution of the components of the reaction mixture until a clear solution is formed very slowly poured dropwise 1 ml of methanol as the first precipitator, and then 5 ml of the propyl alcohol - as the second. 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 0.07 g of white powder. The yield was 85%.

EXAMPLE 7. Obtaining microcapsules of cefepime in human leukocyte interferon (β-IFN) using methanol and isopropyl alcohol as a precipitating, the ratio of 3:1

To 2.5 g of 1% aqueous solution of human leukocyte interferon (β-IFN) add 0.075 g of cefepime powder and 0.05 g of the drug A with as surfactants. The resulting mixture was put on a magnetic stirrer and include mixing. After the dissolution of the components of the reaction mixture until a clear solution is formed very slowly poured dropwise 1 ml of methanol as the first precipitator, and then 5 ml of isopropyl alcohol as the second. 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 0,099 g of white powder. The yield was 99%.

EXAMPLE 8. Obtaining microcapsules of cefepime in human leukocyte interferon (α-IFN) using methanol and isopropyl alcohol as a precipitating, the ratio of 3:1

To 2 g of 1% aqueous solution of inter is erona human leukocyte (α-interferon) add to 0.060 g of cefepime powder and 0.05 g of the drug A with as surfactants. The resulting mixture was put on a magnetic stirrer and include mixing. After the dissolution of the components of the reaction mixture until a clear solution is formed very slowly poured dropwise 1 ml of methanol as the first precipitator, and then 5 ml of isopropyl alcohol as the second. 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 0.08 g of white powder. The yield was 99%.

The obtained microcapsules drug group cephalosporins related to β-lactam antibiotics, α - and β-Tomah of human leukocyte interferon. The process is simple to perform and lasts for 15 minutes, requires no special equipment.

It should be noted that obtaining microcapsules of water-soluble drugs in water-soluble polymers is a particularly difficult task. To achieve this goal, the selection of the method of production of microcapsules. For microencapsulation was selected physico-chemical method due to expressnet and ease of execution.

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, α - and β-Tomah interferon is ilovecosmo leukocyte.

The method of producing microcapsules drugs group of cephalosporins in the shell of interferon, characterized by the fact that 2 g or 2.5 g 1%aqueous solution of human leukocyte interferon in the α - or β-form added 0.06 g or 0.075 g, respectively cephalosporin powder and 0.05 g of the drug Is as a surfactant, the resulting mixture is stirred until complete dissolution of the components of the reaction mixture after formation of a clear solution is slowly poured dropwise 1 ml of methanol as the first precipitator, and then 5 ml of isopropyl alcohol as the second precipitator, filtered off, washed with acetone and dried.



 

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3 ex

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21 cl, 4 tbl, 2 ex, 2 dwg

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4 ex, 3 tbl

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12 cl, 1 tbl, 13 dwg, 196 ex

FIELD: medicine.

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13 cl, 1 dwg, 1 ex

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7 cl, 9 ex, 3 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutical industry, particularly to a medicine for treating depression. The oral medicine for treating depression prepared from a jujuba extract containing jujube cyclic adenosine monophosphate (jujuba cAMP) and an additional ingredient taken from a group consisting of a pharmaceutically acceptable carrier, an additive, an adjuvant and combination thereof. A method for preparing jujube cyclic adenosine monophosphate (jujuba cAMP) taken as an ingredient of the medicine for treating depression, involving the stages: (a) jujube extraction in water and alcohol to produce a primary extract, (b) primary extract purification to produce a secondary extract wherein the jujuba cAMP concentration in the secondary extract is higher than that in the primary extract wherein the stage (b) is performed by jujuba cAMP chromatography of the primary extract with the use of macroporous resins bound with an aldehyde group.

EFFECT: medicine is effective for treating depression, has no side effects.

16 cl, 7 dwg, 2 tbl, 9 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutics and represents a method of preventing and treating oral inflammation following a dental surgery, comprising in applying a drug preparation on an incisional wound daily in a patient underwent the implantation procedure and characterised by the fact that the drug preparation used represents a preparation of the strain lactobacillus plantarum 8P-AZ and/or B.bifidum in a dose of at least 10 million live lactic acid bacilli and/or bifidus bacteria.

EFFECT: invention provides simplifying the method of preventing and treating the oral inflammation by making it unnecessary to prepare the drug used if antibiotics are avoided.

2 cl, 9 ex, 9 dwg

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