RU2799798C1 - Method of obtaining sel-plex nanocapsules in corn starch - Google Patents

Abstract

FIELD: nanotechnology; veterinary medicine.

SUBSTANCE: method of obtaining Sel-Plex nanocapsules in corn starch is proposed. Corn starch is used as the shell, and Sel-Plex is used as the core, with a core:shell mass ratio of 1:3, or 1:1, or 1:2. At the same time, Sel-Plex is added to a suspension of corn starch in petroleum ether in the presence of E472c as a surfactant with stirring at 800 rpm. Next, acetonitrile is added, the resulting suspension is filtered off and dried at a room temperature.

EFFECT: invention is aimed at simplifying and accelerating the process of obtaining nanocapsules, reducing losses when obtaining nanocapsules of a certain size.

1 cl, 3 tbl, 4 ex

Description

The invention relates to the field of nanotechnology and veterinary medicine, in particular the production of Sel-Plex nanocapsules.

Sel-Plex contains selenium mainly in the amino acids selenomethionine and selenocystin. It increases the antioxidant status of the body and the viability of young animals, maintains and increases the mobility and fertilizing ability of sperm, improves productivity in the presence of mycotoxins in feed, improves the condition of plumage. It is 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 obtaining microcapsules of drugs. So, in Pat. 2092155, IPC A61K 047/02, A61K 009/16, Russian Federation, publ. On 10/10/1997, a method for microencapsulation of medicines based on the use of ultraviolet irradiation was proposed.

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

In Pat. 2091071, IPC A61K 35/10, Russian Federation, publ. 09/27/1997, a method for obtaining the drug by dispersing in a ball mill to obtain microcapsules was proposed.

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

In Pat. 2101010, IPC A61K 9/52, A61K 9/50, A61K 9/22, A61K 9/20, A61K 31/19, Russian Federation, publ. 01/10/1998, a chewable form of a drug with taste masking, which has the properties of a controlled release of a drug, contains microcapsules 100-800 microns in diameter and consists of a pharmaceutical core with crystalline ibuprofen and a polymer coating, including a plasticizer, elastic enough to resist chewing. The polymer coating is a copolymer based on methacrylic acid.

Disadvantages of the invention: the use of a copolymer based on methacrylic acid is capable of causing cancerous tumors, and there is also a great complexity of execution and duration of the process.

In Pat. 2173140, IPC A61K 009/50, A61K 009/127, Russian Federation, publ. 09/10/2001, a method for obtaining silicon organolipid microcapsules using a rotary cavitation installation with high shear forces and powerful hydroacoustic phenomena of the sound and ultrasonic range for dispersion is proposed.

The disadvantage of this method is the use of special equipment - a rotary cavitation installation, which has an ultrasonic effect, which affects the formation of microcapsules and at the same time can cause side reactions due to the fact that ultrasound has a destructive effect on polymers of a protein nature, therefore, the proposed method is applicable when working with polymers of synthetic origin.

In Pat. 2359662, IPC A61K 009/56, A61J 003/07, B01J 013/02, A23L 001/00, Russian Federation, publ. On June 27, 2009, a method for producing microcapsules using spray cooling in a Niro spray cooling tower was proposed under the following conditions: inlet air temperature 10°C, outlet air temperature 28°C, spray drum rotation speed 10,000 rpm. The microcapsules of the invention have improved stability and provide controlled and/or sustained 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 (inlet air temperature 10°C, outlet air temperature 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, Russian Federation, publ. August 27, 1999 (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 leads to a simplification of the microencapsulation method.

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

The technical problem is the simplification and acceleration of the process of obtaining nanocapsules, reducing losses in the production of microcapsules (increasing the yield by weight).

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

A distinctive feature of the proposed method is the use of corn starch as a shell of Sel-Plex nanocapsules - as their core, as well as the use of a precipitant - acetonitrile.

EXAMPLE #1. Preparation of Sel-Plex nanocapsules in corn starch, core:shell ratio 1:3

100 mg of Sel-Plex are suspended in a suspension of 300 mg of corn starch in petroleum ether, in the presence of 0.01 g of E472c (an ester of glycerol with one or two molecules of edible fatty acids and one or two molecules of citric acid, and citric acid, as tribasic, can be esterified with other glycerides and as oxo acid with other fatty acids. Free acid groups can be neutralized with sodium) with stirring at 800 rpm. Then add 4 ml of acetonitrile. The resulting suspension is filtered and dried at room temperature.

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

From the data in Table 1 it can be seen that their average size is 156.8 nm, of which D10 is 29.9; D50 - 49.6; D90 - 301.3, in 1 ml, with a total concentration of 17.10 × 10 to the twelfth degree. Polydispersity coefficient - 5.47.

Table 1. Statistical characteristics of distributions in a sample of Sel-Plex nanocapsules in corn starch (core:shell ratio 1:3) Parameter Meaning Average size, nm 156.8 D10, nm 29.9 D50, nm 49.6 D90, nm 301.3 Polydispersity coefficient, (D90-D10)/D50 5.47 Total concentration of particles, ×10 ⁸ particles/ml 17.10

EXAMPLE #2. Preparation of Sel-Plex nanocapsules in corn starch, core:shell ratio 1:2

100 mg of Sel-Plex are added to a solution of 200 mg of corn starch in petroleum ether in the presence of 0.01 g of E472c with stirring at 800 rpm. Then add 4 ml of acetonitrile. The resulting suspension is filtered and dried at room temperature.

Received 0.3 g of white with a yellowish tint of powder. The yield was 99%.

From the data in Table 2 it can be seen that their average size is 83.8 nm, of which D10 is 18.5; D50 - 25; D90 - 152.5, in 1 ml, with a total concentration of 10.80 × 10 to the twelfth degree. Polydispersity coefficient - 5.36.

Table 2. Statistical characteristics of distributions in a sample of Sel-Plex nanocapsules in corn starch (core:shell ratio 1:2) Parameter Meaning Average size, nm 83.5 D10, nm 18.5 D50, nm 25 D90, nm 152.5 Polydispersity coefficient, (D90-D10)/D50 5.36 Total concentration of particles, ×10 ⁸ particles/ml 10.80

EXAMPLE #3. Preparation of Sel-Plex nanocapsules in corn starch, core:shell ratio 1:1

100 mg of Sel-Plex are dispersed in a solution of 100 mg of corn starch in petroleum ether in the presence of 0.01 g of E472c with stirring at 800 rpm. Then add 4 ml of acetonitrile. The resulting suspension is filtered and dried at room temperature.

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

From the data in Table 3 it can be seen that their average size is 187.8 nm, of which D10 is 29.9; D50 - 49.6; D90 - 301.3, in 1 ml, with a total concentration of 29.70 × 10 to the twelfth degree. Polydispersity coefficient - 5.47.

Table 3. Statistical characteristics of distributions in a sample of Sel-Plex nanocapsules in corn starch (core:shell ratio 1:1) Parameter Meaning Average size, nm 187.8 D10, nm 29.9 D50, nm 49.6 D90, nm 301.3 Polydispersity coefficient, (D90-D10)/D50 5.47 Total concentration of particles, ×10 ⁸ particles/ml 29.70

EXAMPLE #4. Determination of the sizes of nanocapsules by the NTA method

The measurements were carried out on a Nanosight LM0 multiparametric nanoparticle analyzer manufactured by Nanosight Ltd (Great Britain) in the HS-BF configuration (high-sensitivity Andor Luca video camera, semiconductor laser with a wavelength of 405 nm and a power of 45 mW). The instrument is based on the Nanoparticle Tracking Analysis (NTA) method described in ASTM E2834.

The optimal dilution for breeding was chosen 1:100. The following instrument parameters were selected for measurement: Camera Level = 16, Detection Threshold = 10 (multi), Min Track Length: Auto, Min Expected Size: Auto, single measurement duration 215 s, use of a syringe pump.

Claims (1)

A method for producing Sel-Plex nanocapsules in corn starch, characterized in that corn starch is used as the shell, and Sel-Plex is used as the core, at a core:shell mass ratio of 1:3, or 1:1, or 1:2, while Sel-Plex is added to a suspension of corn starch in petroleum ether in the presence of E472c as a surfactant with stirring at 800 rpm, then acetone is added ytrile, the resulting suspension is filtered and dried at room temperature.