RU2641190C1 - Method for producing nanocapsules of dry extract of topinambur - Google Patents

Abstract

FIELD: nanotechnology.SUBSTANCE: method for obtaining nanocapsules of a dry extract of Jerusalem artichoke in a shell of pectin is described. As a nanocapsule, a low-esterified and highly esterified apple and citrus pectin is used, as a core - a dry extract of Jerusalem artichoke. Nanocapsules are prepared by mixing a mixture of pectin in toluene with 0.01 g of E472c as a surfactant, then adding a dry extract of Jerusalem artichoke into the mixture, precipitating with diethyl ether, followed by filtering out the resulting suspension and drying the nanocapsules. Mass ratio in nanocapsules core: shell is 1:3 or 5:1. The process of obtaining nanocapsules is carried out at 25°C for 15 minutes.EFFECT: simplification and acceleration of the nanocapsules production process and increase in yield by weight.4 dwg, 9 ex

Description

The invention relates to the field of nanotechnology of the food industry.

Previously known methods for producing microcapsules of drugs. So, in US 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 special equipment using 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. 2095055, IPC A61K 9/52, A61K 9/16, A61K 9/10, Russian Federation, published 10.11.1997, a method for producing solid non-porous microspheres includes melting a pharmaceutically inactive carrier substance, dispersing the pharmaceutically active substance in a melt in an inert atmosphere, spraying the resulting dispersion in the form of fog in a 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. A suspension intended for administration by parenteral injection contains an effective amount of said microspheres distributed in a pharmaceutically acceptable liquid vector, the pharmaceutically active substance of the microsphere being insoluble in said liquid medium.

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

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 disadvantages of the method are the use of a ball mill and the duration of the process.

In US Pat. 2076765, IPC B01D 9/02, Russian Federation, published April 10, 1997. A method for producing dispersed particles of soluble compounds in microcapsules by crystallization from a solution is proposed, characterized in that the solution is dispersed in an inert matrix, cooled, and dispersed particles are obtained by changing the temperature.

The disadvantage of this method is the difficulty of execution: obtaining microcapsules by dispersion with subsequent change in temperature, which slows down 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; obtaining microcapsules by suspension polymerization; complexity of execution; the duration of the process.

In US Pat. 2139046, IPC A61K 9/50, A61K 49/00, A61K 51/00, Russian Federation, published 10.10.1999, a method for producing microcapsules as follows. An oil-in-water emulsion is prepared from an organic solution containing dissolved mono-, di-, triglyceride, preferably tripalmitin or tristearin, and possibly a therapeutically active substance, and an aqueous solution containing a surfactant, possibly a portion of the solvent is evaporated, a redispersing agent is added the agent and the mixture are freeze dried. The freeze-dried mixture is then redispersed in an aqueous carrier to separate the microcapsules from organic residues, and the hemispherical or spherical microcapsules are dried.

The disadvantages of the proposed method are the complexity and duration of the process, the use of freeze-drying, which takes a lot of time and slows down the process of obtaining microcapsules.

In US Pat. 2159037, IPC A01N 25/28, A01N 25/30, Russian Federation, published November 20, 2000. A method for producing microcapsules by a polymerization reaction at the phase boundary containing a solid agrochemical material of 0.1-55 wt. % suspended in a water-miscible organic liquid, 0.01-10 wt. % non-ionic dispersant active at the phase boundary and not acting as an emulsifier.

The disadvantages of the proposed method: complexity, duration, the use of high shear mixer.

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. ES WO / 2010/076360, IPC B01J 13/00; A61K 9/14; A61K 9/10; A61K 9/12, published July 8, 2010. A new method is proposed for producing solid micro- and nanoparticles with a homogeneous structure with a particle size of less than 10 μm, where the treated solid compounds have a natural crystalline, amorphous, polymorphic and other states associated with the starting compound. The method allows one to obtain solid micro- and nanoparticles with substantially spheroidal morphology.

The disadvantage of the proposed method is the complexity of the process, which leads to capsules with a floating output.

In US Pat. EP WO / 2010/119041, IPC A23L 1/00, published October 21, 2010, a method for producing beads containing an active component encapsulated in a gel matrix of a whey protein comprising denatured protein, serum and active components is proposed. The invention relates to a method for producing beads that contain components such as probiotic bacteria. A method for producing microspheres includes the stage of production of microspheres in accordance with the method of the invention and subsequent curing of the microspheres in a solution of anionic polysaccharide with a pH of 4.6 or lower for at least 10, 30, 60, 90, 120, 180 minutes. Examples of suitable anionic polysaccharides: pectins, alginates, carrageenans. Ideally, whey protein is heat denaturing, although other denaturation methods are also applicable, for example, pressure-induced denaturation. In a preferred embodiment, the whey protein is denatured at a temperature of from 75 ° C to 80 ° C, appropriately for 30 minutes to 50 minutes. As a rule, whey protein is mixed with heat denaturation. Accordingly, the concentration of whey protein is from 5 to 15%, preferably from 7 to 12%, and ideally from 9 to 11% (weight / volume). Typically, the process is carried out by filtration through multiple filters with a gradual reduction in pore size. Ideally, a fine filter has submicron pore sizes, for example from 0.1 to 0.9 microns.

The preferred method for producing beads is a method using vibratory encapsulators (Inotech, Switzerland) and machines manufactured by Nisco Engineering AG. As a rule, nozzles have openings of 100 and 600 microns, and ideally about 150 microns.

The disadvantage of this method is the use of special equipment (vibration encapsulators (Inotech, Switzerland)), the production of microcapsules by protein denaturation, the difficulty of isolating the microcapsules obtained by this method is filtration using multiple filters, which makes the process long.

In US Pat. EP WO / 2011/003805, IPC B01J 13/18; B65D 83/14; C08G 18/00 describes a method for producing microcapsules that are suitable for use in formulations of sealants, foams, coatings or adhesives.

The disadvantage of the proposed method is the use of centrifugation to separate from the process fluid, the duration of the process, as well as the use of this method not in the pharmaceutical industry.

In US Pat. 20110223314, IPC B05D 7/00 20060101 B05D 007/00, B05C 3/02 20060101 B05C 003/02; B05C 11/0020060101 B05C 011/00; B05D 1/18 20060101 B05D 001/18; B05D 3/0220060101 B05D 003/02; B05D 3/06 20060101 B05D 003/06 dated 03/10/2011, US describes a method for producing microcapsules by suspension polymerization, which belongs to the group of chemical methods using a 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 US Pat. US WO / 2011/150138, IPC C11D 3/37; B01J 13/08; C11D 17/00, published December 1, 2011 describes a method for producing microcapsules of solid water-soluble agents by polymerization.

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

In US Pat. US WO / 2011/127030, IPC A61K 8/11; B01J 2/00; B01J 13/06; C11D 3/37; C11D 3/39; C11D 17/00, published October 13, 2011. Several methods for producing microcapsules are proposed: interfacial polymerization, thermo-induced phase separation, spray drying, evaporation of the solvent, etc. The disadvantages of the proposed methods are the complexity, duration of the processes, and the use of special equipment (filter (Albet, Dassel , Germany), a spray dryer for collecting particles (Spray-4M8 Dryer from ProCepT, Belgium)).

The disadvantages of the proposed methods are the complexity, duration of the processes, as well as the use of special equipment (filter (Albet, Dassel, Germany), a spray dryer for collecting particles (Spray-4M8 Dryer from ProCepT, Belgium)).

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 of dry Jerusalem artichoke extract in pectin, reduce losses in obtaining nanocapsules (increase in yield by mass).

The solution to the technical problem is achieved by the method of producing nanocapsules of Jerusalem artichoke dry extract, characterized in that pectins are used as the nanocapsule shell, as well as by the production of nanocapsules by the physicochemical precipitation method with a non-solvent using a precipitant - diethyl ether, the production process is carried out without special equipment.

A distinctive feature of the proposed method is the use of a Jerusalem artichoke dry extract and pectins as a shell of nanocapsules, as well as the preparation of nanocapsules by the physicochemical method of precipitation with a non-solvent using a precipitator - diethyl ether.

The result of the proposed method is to obtain nanocapsules of dry Jerusalem artichoke extract in pectins at 25 ° C for 15 minutes. The yield of nanocapsules is 100%.

EXAMPLE 1. Obtaining nanocapsules of dry Jerusalem artichoke extract in apple low esterified pectin, ratio 1: 3

To 3 g of a suspension of low esterified apple pectin in toluene, 0.01 g of the preparation E472c, 1 g of dry Jerusalem artichoke extract is added as a surfactant. Then add 5 ml of diethyl ether. The resulting suspension of nanocapsules is filtered and dried.

Received 4 g of cream powder. The yield was 100%.

EXAMPLE 2. Obtaining nanocapsules of dry Jerusalem artichoke extract in apple highly esterified pectin, ratio 1: 3

To 3 g of a suspension of highly esterified julienne pectin in toluene, 0.01 g of the preparation E472c, 1 g of dry Jerusalem artichoke extract is added as a surfactant. Then add 5 ml of diethyl ether. The resulting suspension of nanocapsules is filtered and dried.

Received 4 g with a creamy tint of powder. The yield was 100%.

EXAMPLE 3. Obtaining nanocapsules of dry Jerusalem artichoke extract in citrus low esterified pectin, ratio 1: 3

To 3 g of a suspension of low etherification citrus pectin in toluene, 0.01 g of the preparation E472c, 1 g of dry Jerusalem artichoke extract is added as a surfactant. Then add 5 ml of diethyl ether. The resulting suspension of nanocapsules is filtered and dried.

Received 4 g of a white powder. The yield was 100%.

EXAMPLE 4. Obtaining nanocapsules of dry Jerusalem artichoke extract in citrus high-esterified pectin, ratio 1: 3

To 3 g of a suspension of highly esterified citrus pectin in toluene, 0.01 g of the preparation E472c, 1 g of dry Jerusalem artichoke extract is added as a surfactant. Then add 5 ml of diethyl ether. The resulting suspension of nanocapsules is filtered and dried.

Received 4 g of a white with cream tint powder. The yield was 96.25%.

EXAMPLE 5. Obtaining nanocapsules of dry Jerusalem artichoke extract in apple low esterified pectin, ratio 5: 1

To 1 g of a suspension of low esterified apple pectin in toluene, 0.01 g of the preparation E472c, 5 g of dry Jerusalem artichoke extract is added as a surfactant. Then add 6 ml of diethyl ether. The resulting suspension of nanocapsules is filtered and dried.

Received 6 g of cream powder. The yield was 100%.

EXAMPLE 6. Obtaining nanocapsules of dry Jerusalem artichoke extract in apple highly esterified pectin, ratio 5: 1

To 1 g of a suspension of highly esterified apple pectin in toluene, 0.01 g of the preparation E472c, 5 g of dry Jerusalem artichoke extract is added as a surfactant. Then add 6 ml of diethyl ether. The resulting suspension of nanocapsules is filtered and dried.

Received 6 g with a creamy powder tint. The yield was 100%.

EXAMPLE 7. Obtaining nanocapsules of dry Jerusalem artichoke extract in citrus low esterified pectin, ratio 5: 1

To 1 g of a suspension of low etherification citrus pectin in toluene, 0.01 g of the preparation E472c, 5 g of dry Jerusalem artichoke extract is added as a surfactant. Then add 6 ml of diethyl ether. The resulting suspension of nanocapsules is filtered and dried.

Received 6 g of a white powder. The yield was 100%.

EXAMPLE 8. Obtaining nanocapsules of dry Jerusalem artichoke extract in citrus high-esterified pectin, ratio 5: 1

To 1 g of a suspension of highly esterified citrus pectin in toluene, 0.01 g of the preparation E472c, 5 g of dry Jerusalem artichoke extract is added as a surfactant. Then add 6 ml of acetonitrile. The resulting suspension of nanocapsules is filtered and dried.

Received 6 g of a white with cream tint powder. The yield was 100%.

EXAMPLE 9. Sizing of nanocapsules by the NTA method (see Fig. 1-4).

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

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

Pectins (Е440) are widely used in the production of confectionery jelly and pastry products, for the stabilization of dairy products, in the manufacture of preserves, as well as in bakery and flour confectionery. There is evidence of the use of pectins as stabilizers for the consistency of creams, lotions, shampoos.

The proposed method is suitable for the cosmetic and pharmaceutical industries due to the minimal losses, speed, simplicity of obtaining and isolation of nanocapsules of dry Jerusalem artichoke extract in apple and citrus pectin.

Claims (1)

A method for producing nanocapsules of dry Jerusalem artichoke extract in pectin, characterized in that low esterified and highly esterified apple and citrus pectin are used as the nanocapsule shell, and Jerusalem artichoke dry extract is used as the core, while nanocapsules are prepared by mixing a mixture of pectin in toluene with 0.01 g of E4 as a surfactant, the subsequent addition of Jerusalem artichoke dry extract to the mixture, precipitation with diethyl ether, followed by filtering the resulting suspension and drying the nanocapsules, while the mass ratio in the core: shell nanocapsules is 1: 3 or 5: 1, the process of obtaining nanocapsules is carried out at 25 ° C for 15 minutes.

Images