RU2634256C2 - Method for producing nanocapules of dry extract of topinambur - Google Patents

Abstract

FIELD: nanotechnology.

SUBSTANCE: dry topinambur extract is added to a suspension of agar-agar in ethanol containing 0.01 g of the E472c preparation as a surfactant, stirred at 1000 rpm, then hexane is added, the resulting nanocapsule suspension is filtered, washed with hexane and dried, while the weight ratio of agar-agar to the topinambur extract in nanocapsules is 1:1, 3 1, 5:1 or 1:5.

EFFECT: simplification and acceleration of nanocapsules preparation, reduction of losses during the nanocapsules production.

2 dwg, 5 ex

Description

The invention relates to the field of nanotechnology, in particular nanocapsulation of drugs by the example of dry tapinambur extract in agar-agar.

Previously known methods for producing microcapsules of drugs. So, in US Pat. RF 2092155 IPC A61K 047/02, A61K 009/16 published on 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. RF 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, including melting a pharmaceutically inactive carrier substance, dispersing a pharmaceutically active substance in a melt in an inert atmosphere, spraying the obtained 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. RF 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 disadvantages of the method are the use of a ball mill and the duration of the process.

In US Pat. RF 2076765, IPC B01D 9/02, published 04/10/1997, 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. RF 2101010, IPC A61K 9/52, A61K 9/50, A61K 9/22, A61K 9/20, A61K 31/19, published January 10, 1998 a chewing form of the drug with a taste masking having 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, as these polymer coatings can cause cancerous tumors; obtaining microcapsules by suspension polymerization; complexity of execution; the duration of the process.

In US Pat. RF 2139046, IPC A61K 9/50, A61K 49/00, A61K 51/00, 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 optionally a therapeutically active substance, and an aqueous solution containing a surfactant, optionally a part of the solvent is evaporated, a redispersing agent is added and the mixture is 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. RF 2159037, IPC A01N 25/28, A01N 25/30, published 11/20/2000, a method for producing microcapsules by the polymerization reaction at the interface, containing solid agrochemical material 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. RF 2173140, IPC A61K 009/50, A61K 009/127, 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 - 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. RF 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 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).

In US Pat. ES WO / 2010/076360, IPC B01J 13/00; A61K 9/14; A61K 9/10; AK61K 9/12, published on 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 to obtain solid micro- and nanoparticles with substantially spheroidal morphologists.

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 including 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 an 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, whey protein is denatured at a temperature of from 75 to 80 ° C., suitably 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 - filtering using many 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. US20110223314, IPC B05D 7/00 20060101 B05D 007/00, B05C 3/02 20060101 B05C 003/02; B05C 11/00 20060101 B05C 011/00; B05D 1/18 20060101 B05D 001/18; B05D 3/02 20060101 B05D 003/02; B05D 3/06 20060101 B05D 003/06 dated 03/10/2011 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; C11D3 / 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 ProCert, Belgium)).

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 ProCert, Belgium)).

In US Pat. GB WO / 2011/104526, IPC B01J 13/00; B01J 13/14; С09В 67/00; C09D 11/02, published September 1, 2011. A method for producing a dispersion of encapsulated solid particles in a liquid medium is proposed, including: a) grinding a composition comprising solid, liquid media and polyurethane dispersants with an acid number of from 0.55 to 3.5 mmol per 1 g dispersant, said composition comprises from 5 to 40 parts of a polyurethane dispersant per 100 parts of solid products by weight; and b) crosslinking the polyurethane dispersant in the presence of a solid and liquid medium, as for the encapsulation of solid particles, which polyurethane dispersant contains less than 10% by weight of repeating elements from polymer alcohols.

The disadvantages of the proposed method are the complexity and duration of the process for producing microcapsules, as well as the fact that the encapsulated particles of the proposed method are useful as dyes in ink, especially inkjet inks, for the pharmaceutical industry this technique is not applicable.

In US Pat. US WO / 2011/056935, IPC C11D 17/00; A61K 8/11; B01J 13/02; C11D 3/50, published May 12, 2011 describes a method for producing microcapsules with a size of 15 microns or more. Polymers of the group consisting of polyethylene, polyamides, polystyrenes, polyisoprenes, polycarbonates, polyesters, polyacrylates, polyureas, polyurethanes, polyolefins, polysaccharides, epoxies, vinyl polymers and mixtures thereof are proposed as a shell material. The proposed polymer shells are sufficiently impervious to the core material and materials in the environment in which the agent is encapsulated, the benefit will be used to provide the benefits that will be obtained. The core of encapsulated agents may include perfumes, silicone oils, waxes, hydrocarbons, higher fatty acids, essential oils, lipids, skin cooling fluids, vitamins, sunscreens, antioxidants, glycerin, catalysts, bleaching particles, particles of silicon dioxide, etc.

The disadvantages of the proposed method are the complexity, duration of the process, the use as shells of microcapsules of polymers of synthetic origin and their mixtures.

The closest method is the method proposed in US Pat. RF 2134967, IPC A01N 53/00, A01N 25/28, 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 technical task is to simplify and accelerate the process of obtaining nanocapsules of dry tapinambur extract in agar-agar, reducing losses in obtaining nanocapsules (increase in yield by mass).

The solution of the technical problem is achieved by the method of producing nanocapsules of dry tapinambur extract, characterized in that agar-agar is used as the shell of the nanocapsules, as well as the preparation of nanocapsules by the physicochemical method of precipitation with a non-solvent using a precipitator - hexane.

A distinctive feature of the proposed method is the use of a dry extract of tapinambur, agar-agar as a shell of nanocapsules, as well as the preparation of nanocapsules by the physicochemical method of precipitation with a non-solvent using hexane precipitant.

The result of the proposed method is the preparation of nanocapsules of dry tapinambur extract in agar-agar at 25 ° C for 15 min. The yield of nanocapsules is 100%.

Example 1. Obtaining nanocapsules of dry Jerusalem artichoke extract, the ratio of core: shell 1: 3

To 3 g of a suspension of agar-agar in ethanol, add 0.01 g of the preparation E472c as a surfactant. The resulting mixture is placed on a magnetic stirrer and include stirring. 1 g of dry extract of tapinambur is slowly added in portions to a suspension of agar-agar in ethanol and stirred at 1000 rpm. Then add 5 ml of hexane. The resulting suspension of nanocapsules is filtered off on a filter, washed with hexane, and dried.

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

Example 2. Obtaining nanocapsules of dry extract of tapinambur, the ratio of core: shell 1: 1

To 1 g of a suspension of agar-agar in ethanol, add 0.01 g of the preparation E472c as a surfactant. The resulting mixture is placed on a magnetic stirrer and include stirring. 1 g of dry extract of tapinambur is transferred to a suspension of agar-agar in ethanol and stirred at 1000 rpm. Then add 5 ml of hexane. The resulting suspension of nanocapsules is filtered off on a filter, washed with hexane, and dried.

Received 2 g of powder with a cream tint. The yield was 100%.

Example 3. Obtaining nanocapsules of dry extract of tapinambur, the ratio of the core: shell 1: 5

To 5 g of a suspension of agar-agar in ethanol, add 0.01 g of the preparation E472c as a surfactant. The resulting mixture is placed on a magnetic stirrer and include stirring. 1 g of dry extract of tapinambur is transferred to a suspension of agar-agar in ethanol and stirred at 1000 rpm. Then add 10 ml of hexane. The resulting suspension of nanocapsules is filtered off on a filter, washed with hexane, and dried.

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

Example 4 Preparation of Nanocapsules of Tapinambur Dry Extract, Core: Shell Ratio 5: 1

To 1 g of a suspension of agar-agar in ethanol, add 0.01 g of the preparation E472c as a surfactant. The resulting mixture is placed on a magnetic stirrer and include stirring. 5 g of dry extract of tapinambur is transferred to a suspension of agar-agar in ethanol and stirred at 1000 rpm. Then add 10 ml of hexane. The resulting suspension of microcapsules is filtered off on a filter, washed with hexane, and dried.

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

E472c is a glycerol ester with one or two molecules of edible fatty acids and one or two molecules of citric acid, moreover, citric acid, as tribasic, can be esterified with other glycerides and, like oxoacid, with other fatty acids. Free acid groups can be neutralized with sodium.

The proposed technique is suitable for the cosmetic and pharmaceutical industries due to minimal losses, speed, ease of preparation and isolation of nanocapsules of dry tapinambur extract in agar-agar.

Claims (1)

A method of producing nanocapsules of dry Jerusalem artichoke extract in agar-agar, characterized in that the Jerusalem artichoke dry extract is added to a suspension of agar-agar in ethanol containing 0.01 g of the preparation E472c as a surfactant, stirred at 1000 rpm, then added hexane, the resulting suspension of nanocapsules is filtered off, washed with hexane and dried, while the mass ratio of agar-agar to Jerusalem artichoke extract in nanocapsules is 1: 1, 3: 1, 5: 1 or 1: 5.

Images