RU2592203C1 - Method of producing nanocapsules of sulphur - Google Patents

Abstract

FIELD: nanotechnology.

SUBSTANCE: invention relates to encapsulation. Described is a method of producing nanocapsules of sulphur. According to method disclosed herein, sulphur is added to sodium alginate suspension in butanol in presence of E472c preparation while mixing. Precipitator - sulphuric ether - is added. Obtained suspension of nanocapsules is filtered and dried. Process of nanoencapsulation is performed at 25 °C for 20 minutes.

EFFECT: invention provides implementation of purposes.

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Description

The invention relates to the field of nanotechnology and can be used in veterinary medicine.

Previously known methods for producing microcapsules of drugs. So, in RF patent No. 2092155 (IPC A61K047 / 02, A61K009 / 16, published 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 the patent of the Russian Federation No. 2091071 (IPC A61K35 / 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 the patent of the Russian Federation No. 2101010 (IPC A61K9 / 52, A61K9 / 50, A61K9 / 22, A61K9 / 20, A61K31 / 19, published January 10, 1998) a chewing form of the drug with a taste masking that has the properties of a controlled release of the drug contains microcapsules 100 to 800 microns in diameter and consists of a pharmaceutical core with crystalline ibuprofen and a polymer coating that includes a plasticizer that is 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, as these polymer coatings can cause cancerous tumors; complexity of execution, duration of the process.

In the patent of the Russian Federation No. 2173140 (IPC A61K009 / 50, A61K009 / 127, published September 10, 2001), a method for producing silicon organolipid microcapsules using a rotary-cavitation unit 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 - 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 RF patent No. 2359662 (IPC A61K009 / 56, A61J003 / 07, B01J013 / 02, A23L001 / 00, published June 27, 2009) a method for producing microcapsules using spray cooling in a Niro spray cooling tower under the following conditions: inlet air temperature 10 ° C, outlet air temperature 28 ° C, the 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 known method proposed in the patent of the Russian Federation No. 21394967 (IPC A01N53 / 00, A01N25 / 28, published on 08.27.1999). A solution of a mixture of natural lipids and a 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 closest is a method of encapsulating creatine with supramolecular properties according to the patent of the Russian Federation No. 2538695 (IPCA61K9 / 50, A61K35 / 12, A61K9 / 52, B01J13 / 06, published January 10, 2015), in which to create capsules creatine is dispersed in a suspension of sodium alginate in butanol in the presence of the preparation E472c (glycerol ester with one or two molecules and food fatty acids and one or two molecules of citric acid, moreover, citric acid as a tribasic acid can be esterified with other glycerides and as an acid with other fatty acids; Water transportation acid groups may be neutralized with sodium) while stirring 1000 rpm / s. Chloroform is used as precipitant. The resulting precipitate was filtered off and dried at room temperature.

The technical task is to develop a method for producing sulfur nanocapsules.

The technical result is the implementation of the purpose of the technical task.

The solution of the technical problem is achieved by the proposed method for producing sulfur nanocapsules, in which sulfur is dispersed in a suspension of sodium alginate in butanol in the presence of the preparation E472c (glycerol ester with one or two molecules and food fatty acids and one or two molecules of citric acid, with citric acid as a tribasic can be esterified with other glycerides and, as an acid, with other fatty acids; free acid groups can be neutralized with sodium) with stirring at 1000 rpm. Sulfur ether is used as precipitant. The resulting precipitate was filtered off and dried at room temperature.

A distinctive feature of the proposed method is the use of sodium alginate as a shell of nanocapsules, sulfur - as their core, as well as the use of a precipitant - sulfur ether.

Sulfur ether, as a rule, is used as a solvent for cellulose nitrates (including in the manufacture of smokeless powder), animal and vegetable fats, natural and synthetic resins, alkaloids, etc .; as well as an extractant, for example, for the separation of Pu and its fission products in the preparation and processing of nuclear fuel, in the separation of U from ores; as an anesthetic in medicine.

The use of sulfuric ether as a precipitant of sulfur nanocapsules is not known from the prior art, therefore, the claimed technical solution meets the conditions of novelty and inventive step.

The present invention meets the industrial applicability condition, because the method is characterized by simplicity, does not require special hardware design, while the mixing speed is lower than that of the prototype, and equal to 1000 rpm, and the duration of the process is not more than 20 minutes.

To confirm that nanocapsules were obtained during the implementation of the method, capsule sizes were determined by the NTA method on a Nanosight LM0 multi-parameter nanoparticle analyzer manufactured by Nanosight Ltd (Great Britain) in the HS-BF configuration (Andor Luca high-sensitivity video camera, 405 nm semiconductor laser and power 45 mW). The device is based on the Nanoparticle Tracking Analysis (NTA) method described in ASTM E2834. The optimal dilution of 1: 100 and the instrument parameters were selected for measurement: Camera Level = 16, Detection Threshold = 10 (multi), Min Track Length: Auto, Min Expected Size: Auto, duration of a single measurement of 215s, use of a syringe pump.

The measurement results are presented in the following graphic images.

Figure 1. Particle size distribution in a sample of sulfur nanocapsules in sodium alginate (core: shell ratio 1: 3)

Figure 2. A table that shows the statistical characteristics of the particle size distributions in the sample of sulfur nanocapsules in a shell of sodium alginate with a core: shell ratio of 1: 3.

The result of the proposed method is to obtain sulfur nanocapsules in sodium alginate at 25 ° C for 20 minutes. The yield of nanocapsules is more than 90%.

Examples of carrying out the invention

EXAMPLE 1. Obtaining sulfur nanocapsules, the ratio of core / polymer 1: 3

100 mg of sulfur is dispersed in a suspension of sodium alginate in butanol containing the indicated 300 mg of polymer in the presence of 0.01 g of the preparation E472c (glycerol ester with one or two molecules of food fatty acids and one or two molecules of citric acid, with citric acid as a tribasic , can be esterified with other glycerides and as an acid with other fatty acids. Free acid groups can be neutralized with sodium) with stirring at 1000 rpm. Next, 5 ml of sulfuric ether are added. The resulting suspension is filtered and dried at room temperature.

Received 0.4 g of a white with a yellowish tinge of powder. The yield was 100%.

EXAMPLE 2. Obtaining sulfur nanocapsules, the ratio of core / polymer 3: 1

300 mg of sulfur is dispersed in a suspension of sodium alginate in butanol containing the indicated 100 mg of polymer in the presence of 0.01 g of the preparation E472c with stirring at 1000 rpm. Next, 5 ml of sulfuric ether are added. The resulting suspension is filtered and dried at room temperature.

Received 0.4 g of a white with a yellowish tinge of powder. The yield was 100%.

EXAMPLE 3. Obtaining sulfur nanocapsules, the ratio of core / polymer 1: 1

100 mg of sulfur is dispersed in a suspension of sodium alginate in butanol containing the indicated 100 mg of polymer in the presence of 0.01 g of the preparation E472c with stirring at 1000 rpm. Next, 5 ml of sulfuric ether are added. The resulting suspension is filtered and dried at room temperature.

Received 0.2 g of a white with a yellowish tinge of powder. The yield was 100%.

These examples do not limit the application of the invention to only these ratios.

The proposed method can be implemented in industry due to minimal losses, speed and ease of obtaining sulfur nanocapsules, which can be in demand in veterinary medicine.

Claims (1)

A method for producing sulfur nanocapsules, including dispersing sulfur into a suspension of sodium alginate in butanol in the presence of E472c with stirring, adding a precipitant and drying the filtered precipitate at room temperature, characterized in that sulfuric ether is used as a precipitant, and the stirring speed is 1000 rpm.

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