RU2622752C1 - Method for spinage dry extract nanocapules production - Google Patents

Abstract

FIELD: pharmacology.

SUBSTANCE: 1 g of spinage dry extract is added to 1 g or 3 g of sodium alginate suspension in butanol containing 0.01 g of E472c preparation as a surfactant. Then, 5 ml of methylene chloride is added, the resulting nanocapsule suspension is filtered off, washed with methylene chloride and dried.

EFFECT: simplification and acceleration of spinage dry extract nanocapsules obtaining process, increasing their yield by mass.

1 dwg, 3 ex

Description

The invention relates to the field of nanotechnology, in particular nanocapsulation of drugs on the example of a dry extract of spinach in sodium carboxymethyl cellulose physico-chemical method.

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 November 10, 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 separating the resulting 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 01/10/1998, a chewing form of the drug with a taste masking having the properties of a controlled release of the drug The preparation 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. 2139046, IPC A61K 9/50, A61K 49/00, A61K 51/00, Russian Federation, published on 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, add the redispersing 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 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. 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 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 US Pat. 2359662, IPC A61K 009/56, A61J 003/07, B01J 013/02, A23L 001/00, published June 27, 2009, Russian Federation, a method for producing microcapsules using spray cooling in a Niro spray cooling tower under the following conditions: air temperature inlet 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. WO / 2010/076360 ES, IPC B01J 13/00; A61K 9/14; A61K 9/10; A61K 9/12, published July 8, 2010, proposes a new method 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. WO / 2010/119041 EP, IPC A23L 1/00, published October 21, 2010, a method for producing beads containing the 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 the 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, such as pressure-induced denaturation. In a preferred embodiment, the whey protein is denatured at a temperature of from 75 ° C to 80 ° C, appropriately for from 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. A 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. WO / 2011/003805 EP, IPC B01J 3/18; 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 11/00, 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 US, describes a method for producing microcapsules by suspension polymerization, belonging 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. WO / 2011/150138 US, IPC C11D 3/37; B01J 3/08; C11D 17/00, published 01.12.2011, 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. WO / 2011/127030 US, 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 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)).

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 spinach extract in sodium alginate, 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 dry spinach extract, characterized in that sodium alginate is used as the shell of the nanocapsules, as well as by the production of nanocapsules by the physicochemical precipitation method with a non-solvent using a precipitant - methylene chloride.

A distinctive feature of the proposed method is the use of dry spinach extract, sodium alginate as a shell of nanocapsules, as well as the preparation of nanocapsules by the physicochemical method of precipitation with a non-solvent using a precipitant - methylene chloride.

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

EXAMPLE 1. Obtaining nanocapsules of dry spinach extract, the ratio of core: shell 1: 3

To 3 g of a suspension of sodium alginate in butanol containing 0.01 g of the preparation E472c as a surfactant, put on a magnetic stirrer and include stirring. 1 g of dry extract of spinach is slowly added in portions to a suspension of sodium alginate in butanol. Then add 5 ml of methylene chloride. The resulting suspension of nanocapsules is filtered off on a filter, washed with methylene chloride, and dried.

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

EXAMPLE 2. Obtaining nanocapsules of dry spinach extract, the ratio of core: shell 1: 1

1 g of a suspension of sodium alginate in butanol containing 0.01 g of the preparation E472c as a surfactant, put on a magnetic stirrer and include stirring. 1 g of dry extract of spinach is transferred into a suspension of sodium alginate in butanol. Then add 5 ml of methylene chloride. The resulting suspension of nanocapsules is filtered off on a filter, washed with methylene chloride, and dried.

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

PRIMIER 3. Determination of the size of nanocapsules by the NTA method (see Fig. 1)

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, 405 nm semiconductor laser with a power of 45 mW). The device is based on the method of analysis of trajectories of nanoparticles (Nanoparticle Tracking Analysis, NTA) described by bASTM E2834.

The optimal dilution for dilution was 1: 100. For 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 215s, use of a syringe pump.

Nanocapsules of dry spinach extract in sodium alginate were obtained by the physicochemical method of non-solvent precipitation using methylene chloride as non-solvents. The process is simple to execute and lasts for 15 minutes.

Claims (1)

A method for producing nanocapsules of dry spinach extract in sodium alginate, characterized in that 1 g of dry spinach extract is added to 1 g or 3 g of a suspension of sodium alginate in butanol containing 0.01 g of the preparation E472c as a surfactant, then 5 ml of methylene chloride, the resulting suspension of nanocapsules is filtered off on a filter, washed with methylene chloride and dried.

Images