RU2556118C1 - Method for producing sel-plex nanocapsules possessing supramolecular properties - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention describes a method for producing Sel-Plex nanocapsules possessing the supramolecular properties by non-solvent addition, characterised by the fact that Sel-Plex is dissolved in dimethyl sulphoxide; the prepared mixture is dispersed in xanthum gum solution used as a nanocapsule shell, in butanol, in the presence of E472c preparation while stirring at 1000 cycles per second; the mixture is added with the precipitator benzol, filtered and dried at room temperature.

EFFECT: simplifying and accelerating the process of nanoencapsulation and ensuring higher weight yield.

4 ex, 12 dwg

Description

The invention relates to the field of nanotechnology and veterinary medicine, in particular the production of Sel-Plex nanocapsules with supramolecular properties. Sel-Plex contains selenium mainly in the amino acids selenomethionine and selenocystin. It increases the antioxidant status of the body and the vitality of young animals, maintains and increases the motility and fertilizing ability of sperm, improves productivity in the presence of mycotoxins in feed, and improves the state of plumage. They are used in the production of animal feed and premixes as a source of Se instead of sodium selenite and other inorganic compounds of this element for all animal species.

Previously known methods for producing microcapsules of drugs. So, in Pat. 2092155, IPC A61K 047/02, A61K 009/16, published 10.10.1997, the Russian Federation proposed a method of microencapsulation of drugs based on the use of ultraviolet radiation.

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. 2091071, IPC A61K 35/10, Russian Federation, 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. 2101010, IPC A61K 9/52, A61K 9/50, A61K 9/22, A61K 9/20, A61K 31/19, Russian Federation, published January 10, 1998. A chewing form of the drug with a taste masking having the properties of a controlled release of the drug is proposed contains microcapsules with a size of 100-800 microns in diameter and consists of a pharmaceutical core with crystalline ibuprofen and a polymer coating comprising 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, as these polymer coatings can cause cancerous tumors; complexity of execution; the duration of the process.

In US Pat. 2173140, IPC A61K 009/50, A61K 009/127, Russian Federation, 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 - a rotary-quittance installation, 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. 2359662, IPC A61K 009/56, A61J 003/07, B01J 013/02, A23L 001/00, published June 27, 2009. The Russian Federation proposes 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, spray drum rotation speed of 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. 2134967, IPC A01N 53/00, A01N 25/28, published on 08.27.1999, Russian Federation (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 technical task is to simplify and accelerate the process of obtaining nanocapsules, reducing losses in obtaining microcapsules (increase in yield by mass).

The solution to the technical problem is achieved by the Sel-Plex encapsulation method, characterized in that xanthan gum is used as the shell of the nanocapsules when they are obtained by the physicochemical method of precipitation with a non-solvent using a precipitant - benzene, the production process is carried out without special equipment.

A distinctive feature of the proposed method is the use of xanthan gum as a shell of Sel-Plex nanocapsules - as their core, as well as the use of a precipitant - benzene.

The result of the proposed method is to obtain Sel-Plex nanocapsules in xanthan gum for 20 minutes. The yield of nanocapsules is more than 90%.

Figure 1 presents a confocal image of a fractal composition from a solution of Sel-Plex nanocapsules in the shell of xanthan gum (shell: core ratio 3: 1) at a concentration of 0.25%: a) a 505-fold increase, b) a 620-fold increase, a) an increase of 930 times, d) an increase of 1200 times, e) an increase of 1770 times, e) an increase of 2830 times.

Figure 2 presents a confocal image of a fractal composition from a solution of Sel-Plex nanocapsules in the shell of xanthan gum (ratio of shell: core 3: 1) at a concentration of 0.125%: a) an increase of 505 times, b) an increase of 620 times, c) an increase 930 times, d) an increase of 1,200 times, e) an increase of 1,770 times, f) an increase of 2,830 times.

EXAMPLE 1. Obtaining Sel-Plex nanocapsules with dissolution of the drug in dimethyl sulfoxide (DMSO), the ratio of core / polymer 1: 3

100 mg of Sel-Plex is suspended in 1 ml of DMSO and the resulting mixture is dispersed in a solution of xanthan gum 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 food-grade fatty acids and one or two molecules of citric acid, moreover, citric acid as a tribasic acid can be esterified with other glycerides and an oxo acid with other fatty acids. Free acid groups can be neutralized with sodium) with stirring 1000 r / s. Then pour 4 ml of benzene and 1 ml of distilled water. The resulting suspension is filtered and dried at room temperature.

Received 0.396 g of a white powder. The yield was 99%.

EXAMPLE 2. Obtaining nanocapsules Sel-Plex with the dissolution of the drug in dimethyl sulfoxide (DMSO), the ratio of core / polymer 1: 2

100 mg of Sel-Plex was dissolved in 1 ml of DMSO and the resulting mixture was dispersed in a solution of xanthan gum in butanol containing the indicated 200 mg of polymer in the presence of 0.01 g of the preparation E472c with stirring at 1000 r / s. Then pour 3 ml of benzene and 1 ml of distilled water. The resulting suspension is filtered and dried at room temperature.

Received 0.297 g of a white with a yellowish tinge of powder. The yield was 99%.

EXAMPLE 3. Obtaining Sel-Plex nanocapsules with the dissolution of the drug in (DMSO), the ratio of core / polymer 1: 1

100 mg of Sel-Plex is dissolved in 1 ml of DMSO and the resulting mixture is dispersed in a solution of xanthan gum in butanol containing the indicated 100 mg of polymer in the presence of 0.01 g of the preparation E472c with stirring at 1000 r / s. Then pour 2 ml of benzene and 1 ml of distilled water. The resulting suspension is filtered and dried at room temperature.

Received 0.190 g of a white with a yellowish tinge of powder. The yield was 95%.

EXAMPLE 4. The study of the self-organization of nanocapsules from solutions

From the nanocapsule powder obtained by the procedure described in the examples, aqueous solutions were prepared with concentrations of 1%, 0.5%, 0.25%, 0.125%, etc. 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.

The formation of nanocapsules occurs spontaneously due to non-covalent interactions and this suggests that they are characterized by self-assembly. Presented in figure 1, 2, the structures are ordered, which means that they have self-organization. Therefore, the encapsulated Sel-Plex has supramolecular properties.

Sel-Plex nanocapsules were obtained by the physicochemical method of non-solvent deposition using a precipitant, benzene, which helps to increase the yield and accelerates the process of nanocapsulation. 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 preparation and isolation of nanocapsules.

Claims (1)

A method of producing Sel-Plex nanocapsules having supramolecular properties by a non-solvent precipitation method, characterized in that Sel-Plex is dissolved in dimethyl sulfoxide and the resulting mixture is dispersed in a xanthan gum solution used as a nanocapsule shell in butanol in the presence of stirring E472c with stirring 1000 r / s, then precipitant - benzene is added, filtered and dried at room temperature.

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