RU2549956C2 - Method of encapsulating vetom 1,1, possessing supramolecular properties - Google Patents

Abstract

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to field of encapsulation, in particular to method of obtaining microcapsules of medication Vetom 1.1 in carrageenan envelope. According to invention method Vetom 1,1 is dissolved in dimethylsulphoxide, or dimethylformamide, or butanol, obtained mixture is dispersed into solution of carrageenan in butanol in presence of medication E472c with mixing 1000 rev/sec. Vetom 1.1 and carrageenan are taken in weight ratio from 1:1 to 1:5. Then ethanol and distillated water, taken in ratio 5:1 vol/vol, are added. Obtained suspension of microcapsules is filtered and dried. Process of obtaining micro capsules is realised at 25°C for 20 min.

EFFECT: invention ensures simplification and acceleration of process of obtaining microcapsules, reduction of loss in the process of their obtaining (increase of output by weight).

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Description

The invention relates to the field of encapsulation, in particular the production of Vetom 1.1 microcapsules.

Previously known methods for producing microcapsules of drugs. So, in US Pat. RU 2092155? IPC A61K 047/02, A61K 009/16 published on 10/10/1997, a method of microencapsulation of drugs based on the use of ultraviolet radiation is proposed.

The disadvantages of this method are the duration of the process and the use of ultraviolet radiation, which can affect the process of formation of microcapsules.

In US Pat. RU 2091071, IPC A61K 35/10, published 09/27/1997, a method for producing the preparation by dispersion in a ball mill to obtain microcapsules is proposed.

The disadvantage of this method is the use of a ball mill and the duration of the process.

In US Pat. RU 2101010, IPC A61K 9/52, A61K 9/50, A61K 9/22, A61K 9/20, A61K 31/19, published January 10, 1998, there is proposed a chewing form of the drug with a taste mask that has the properties of a controlled release of the drug contains microcapsules with a size of 100-800 microns in diameter and consists of a pharmaceutical core with crystalline ibuprofen and a polymer coating, including a plasticizer, flexible enough to withstand chewing. The polymer coating is a methacrylic acid based copolymer.

The disadvantages of the invention: the use of a copolymer based on methacrylic acid, since these polymer coatings are capable of causing cancerous tumors; complexity of execution; the duration of the process.

In US Pat. RU 2173140, IPC A61K 009/50, A61K 009/127, published September 10, 2001. A method for producing silicon organolipid microcapsules using a rotary-cavitation installation with high shear forces and powerful sonar acoustic and ultrasonic dispersion ranges is proposed.

The disadvantage of this method is the use of special equipment - a rotary cavitation unit, which has an ultrasonic effect, which affects the formation of microcapsules and can cause adverse reactions due to the fact that ultrasound destructively affects polymers of a protein nature, therefore, the proposed method is applicable when work with polymers of synthetic origin.

In US Pat. RU 2359662, IPC A61K 009/56, A61J 003/07, B01J 013/02, A23L 001/00, published June 27, 2009. A method for producing microcapsules using spray cooling in a Niro spray cooling tower is proposed under the following conditions: inlet air temperature 10 ° C, outlet air temperature 28 ° C, rotation speed of the spray drum 10,000 rpm. The microcapsules of the invention have improved stability and provide controlled and / or prolonged release of the active ingredient.

The disadvantages of the proposed method are the duration of the process and the use of special equipment, a set of certain conditions (air temperature at the inlet 10 ° C, air temperature at the outlet 28 ° C, rotation speed of the spray drum 10,000 rpm).

The closest method is the method proposed in US Pat. RU 2134967, IPC A01N 53/00, A01N 25/28, published 08/27/1999, a solution of a mixture of natural lipids and pyrethroid insecticide in a weight ratio of 2-4: 1 in an organic solvent is dispersed in water, which simplifies the microencapsulation method.

The disadvantage of this method is dispersion in an aqueous medium, which makes the proposed method inapplicable for producing microcapsules of water-soluble preparations in water-soluble polymers.

The technical task is to simplify and accelerate the process of obtaining microcapsules, reducing losses when receiving microcapsules (increase in yield by mass).

The solution of the technical problem is achieved by the method of encapsulation of Vetom 1.1, characterized in that carrageenan is used as a shell of microcapsules when they are obtained by the physicochemical method of precipitation with a non-solvent using ethanol as a precipitant, the production process is carried out without special equipment.

A distinctive feature of the proposed method is the use of carrageenan as a shell of Vetom 1.1 microcapsules as their core, as well as the use of ethanol as a precipitant.

The result of the proposed method is to obtain Vetom 1.1 microcapsules in carrageenan at 25 ° C for 20 minutes. The output of microcapsules is more than 90%.

The patent is illustrated by drawings:

FIG. 1. Confocal image of the self-organization of Vetom 1.1 capsules in carrageenan in a ratio of 1: 1, the concentration of 0.5% - a) with an increase of 1770 times, b) with an increase of 2830 times.

FIG. 2. Confocal image of the self-organization of Vetom 1.1 capsules in carrageenan in a ratio of 1: 2, the concentration of 0.5% - a) with an increase of 1770 times, b) with an increase of 2830 times.

FIG. 3. Confocal image of the self-organization of Vetom 1.1 capsules in carrageenan in a ratio of 1: 3, the concentration of 0.5% - a) with an increase of 1770 times, b) with an increase of 2830 times.

EXAMPLE 1. Obtaining Vetom microcapsules 1.1 with the dissolution of the drug in butanol, the ratio of core / polymer 1: 1

100 mg of Vetom 11 is dissolved in 1 ml of butanol and the resulting mixture is dispersed in a solution of carrageenan in 5 ml of butanol containing 100 mg of the indicated polymer in the presence of 0.01 g of the preparation E472c (glycerol ester with one or two food-grade fatty acids and one or two molecules of citric acid, moreover, citric acid, as tribasic, can be esterified with other glycerides and oxoacid with other fatty acids. Free acid groups can be neutralized with sodium) with stirring 1000 r / s. Next, 5 ml of ethanol and 1 ml of distilled water are added. The resulting suspension is filtered and dried at room temperature.

Received 0.178 g of a white powder. The yield was 89%.

EXAMPLE 2. Obtaining Vetom microcapsules 1.1 with the dissolution of the drug in dimethyl sulfoxide (DMSO), the ratio of core / polymer 1: 2

100 mg of Vetom 1.1 is dissolved in 1 ml of DMSO and the resulting mixture is dispersed in a solution of carrageenan in 5 ml of butanol containing 200 mg of the indicated polymer in the presence of 0.01 g of the preparation Е472с with stirring at 1000 r / s. Next, 5 ml of ethanol and 1 ml of distilled water are added. The resulting suspension is filtered and dried at room temperature.

Received 0.267 g of a white powder. The yield was 89%.

EXAMPLE 3. Obtaining Vetom microcapsules 1.1 with the dissolution of the drug in dimethylformamide (DMF), the ratio of core / polymer 1: 3

100 mg of Vetom 1.1 are dissolved in 1 ml of DMF and the resulting mixture is dispersed in a solution of carrageenan in 5 ml of butanol containing 300 mg of the indicated polymer in the presence of 0.01 g of the preparation Е472с with stirring at 1000 r / s. Next, 5 ml of ethanol and 1 ml of distilled water are added. The resulting suspension is filtered and dried at room temperature.

Received 0.356 g of a white powder. The yield was 89%.

EXAMPLE 4. Obtaining Vetom microcapsules 1.1 with dissolution of the drug in dimethyl sulfoxide (DMSO), the ratio of core / polymer 1: 4

100 mg of Vetom 1.1 is dissolved in 1 ml of DMSO and the resulting mixture is dispersed in a solution of carrageenan in 5 ml of butanol containing 400 mg of the indicated polymer in the presence of 0.01 g of the preparation Е472с with 1000 rpm stirring. Next, 5 ml of ethanol and 1 ml of distilled water are added. The resulting suspension is filtered and dried at room temperature.

Received 0.475 g of a white powder. The yield was 95%.

EXAMPLE 5. Obtaining Vetom microcapsules 1.1 with dissolution of the drug in dimethyl sulfoxide (DMSO), the ratio of core / polymer 1: 5

100 mg of Vetom 1.1 is dissolved in 1 ml of DMF and the resulting mixture is dispersed in a solution of carrageenan in 5 ml of butanol containing 500 mg of the indicated polymer in the presence of 0.01 g of the preparation Е472с with 1000 rpm stirring. Next, 5 ml of ethanol and 1 ml of distilled water are added. The resulting suspension is filtered and dried at room temperature.

Received 0.576 g of a white powder. The yield was 96%.

EXAMPLE 6. The study of self-organization of microcapsules from solutions

Aqueous solutions of concentrations of 1%, 0.5%, 0.25%, 0.125%, etc., were prepared from the microcapsule powder obtained by the procedures described in examples 1.2. by diluting the solution in half. A drop of each of the prepared solutions was placed on a glass slide until completely dried, and confocal scanning microscopy was performed on the dried surface.

Vetom 1.1 microcapsules were obtained by the physicochemical non-solvent precipitation method using ethanol as a precipitant, which helps to increase the yield and accelerates the microencapsulation process. The process is simple to execute and lasts for 20 minutes, does not require special equipment.

The proposed technique is suitable for the veterinary industry due to minimal losses, speed, ease of obtaining and isolation of microcapsules.

Vetom 1.1 is a powder, 5 g of which contains:

- corn extract - 2000 mg;

- sucrose - 1000 mg;

- potato starch 1500 mg;

- Bacillus subtilis bacteria (producing interferon α-2-leukocyte human) - 100,000,000 CFU / g - 500 mg.

Claims (1)

The method of encapsulating Vetom 1.1 in a shell of carrageenan, which consists in the fact that the preparation of Vetom 1.1, is dissolved in dimethyl sulfoxide, or dimethylformamide, or butanol, disperses the mixture into a solution of carrageenan in butanol in the presence of E472c with stirring at a mass ratio of 1000 r / s, with a mass ratio core: the specified polymer from 1: 1 to 1: 5, then add ethanol and distilled water, taken in a ratio of 5: 1 vol./about. accordingly, the resulting suspension of microcapsules is filtered and dried, while the process of obtaining microcapsules is carried out at 25 ° C for 20 minutes

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