RU2359662C2 - Microcapsules - Google Patents

Abstract

FIELD: medicine, pharmaceutics. ^ SUBSTANCE: microcapsules, in which water droplet or droplets including the dissolved active ingredient are incapsulated in the hardened hydrophobic cover-matrix, are described. Also the methods of obtaining of the specified microcapsules and their application are described. ^ EFFECT: development of microcapsules which possess the improved stability and provide the adjustable and-or prolonged release of an active ingredient. ^ 40 cl, 8 dwg, 4 tbl, 8 ex

Description

FIELD OF THE INVENTION

The present invention relates to microcapsules, and more particularly, to microcapsules in which an encapsulated water droplet or encapsulated water droplets comprising the active ingredient or active ingredients are further encapsulated in a hydrophobic matrix shell. The present invention also relates to new methods for producing microcapsules of the present invention, as well as the use of microcapsules of the present invention.

State of the art

US 5204029 discloses a method for producing edible microcapsules that contain many liquid cores. In this method, a water-in-oil emulsion in which the active ingredient is dissolved in the internal aqueous phase is spray-cooled, which leads to solidification of the fat phase and capture of the aqueous phase in the form of small droplets dispersed in a microcapsule. However, this method leads to very unstable microcapsules in which the aqueous phase is transferred from the inside of the microcapsule to the outside. It also leads to condensation of water on the container wall.

Kirk-Othmer Encyclopedia of Chemical Technology, 3rd ed., Vol. 15, pp. 473-474, describes a method in which liquids are encapsulated using a rotating extrusion head containing concentric nozzles. This method is only suitable for liquids and suspensions, and large balls are formed containing fusible coatings, such as fats or waxes. However, microcapsules containing a single drop of liquid as a nucleus are very prone to destruction.

In the article by Mofidi N. et al. "Mass preparation and characterization of alginate microspheres". Process Biochemistry, v. 35 (2000), pp. 855-888, described a method for large-scale production of microspheres in which a sterilized alginate solution is prepared and then the solution is added to a reactor containing a non-aqueous phase with stirring. An emulsion of microdroplets of alginate is formed, and an appropriate amount of a crosslinking reagent is added to it. The microspherical particles of the alginate gel sink to the bottom and are collected by filtration.

Similarly, Wong, T.W. et al., J. Microencapsulation, 2002, vol. 19, No. 4, pp. 511-522, described the characteristics of the isolation from pectin microspheres and the method for producing these microspheres. In this method, pectin microspheres are prepared using water-in-oil emulsions in which small pectin microspheres containing the active ingredient dispersed in a continuous liquid hydrophobic phase are solidified and collected by filtration.

A method of microencapsulation by fusion-phase separation is known from Joseph A. Bakan, Controlled Release Technologies, 1980, by Agis F. Kydonieus. The method includes a sequence of three stages carried out with continuous stirring: (1) the formation of three immiscible chemical phases; (2) coating deposition; and (3) coating curing.

Sanghvi, S.P. and Nairn J.G. investigated the effect of viscosity and interfacial surface tension on the particle size of microspheres of cellulose acetate trimellitate. The results are presented in a publication in J. Microencapsulation, 1992, vol. 9, No. 2, pp. 215-227.

In his article in Lebensm.-Wiss.u.-Technol., Vol. 33, pp. 80-88 (2000) Lee, S.J. and Rosenberg, M. described double emulsification and thermal gelation to produce whey protein microcapsules. The microcapsules obtained by the described method are whey protein-based microcapsules containing an apolar core.

In an article in Science, vol. 298, November 1, 2002, Dinsmore et al. Described selective permeability capsules consisting of colloidal particles. Capsules are formed by self-assembly of colloidal particles at the interface of the droplets of the emulsion. After the particles merge to form elastic shells, the droplets of the emulsion are transferred to a fresh, continuous liquid phase, which is the same as that inside the droplets.

The disadvantage of microcapsules and spheres obtained in accordance with the cited publications of Lee et al., Dinsmore et al., Mofidi et al. And Wong et al. Is that these microcapsules are separate microcapsules and, after receiving the microcapsules, the hydrophobic phase is discarded.

The difficulty with prior art microcapsules is that they are very prone to destruction. The shell material can be destroyed, for example, during storage and handling of microcapsules and this leads to the free flow of liquid of the internal phase. The result is a sticky mass and microcapsules are no longer loose powder.

This disruption difficulty can be partially overcome by preparing microcapsules that contain many liquid cores, as described in US 5204029. However, this method still leads to very unstable microcapsules, from the inside of which the aqueous phase migrates outward and then beyond capsules. This additionally leads to condensation of water on the walls of the container. Another microcapsule-related difficulty according to the aforementioned US 5204029 is that it is not possible to control the release of the active ingredient from the microcapsules.

In the present invention, these difficulties for the known microcapsules described above are overcome by microcapsules, which are very stable and provide controlled and / or prolonged release of the active ingredient.

Summary of the invention

The present invention relates to microcapsules comprising a hardened hydrophobic matrix shell, an encapsulated aqueous droplet or droplets that are further encapsulated in or using a hardened hydrophobic membrane shell, and an active ingredient or active ingredients dissolved in or included in an encapsulated aqueous droplet or droplets them, and to methods for their preparation, so as to overcome the above difficulties.

Accordingly, one embodiment of the present invention relates to a microcapsule, which comprises a hardened hydrophobic matrix shell, an encapsulated aqueous droplet or droplets encapsulated in or using a hardened hydrophobic membrane shell, and an active ingredient or active ingredients dissolved in an encapsulated aqueous droplet or droplets or included in them.

Another embodiment of the present invention relates to a method for producing microcapsules, which method comprises the steps of

a) obtaining an aqueous phase and an active ingredient or active ingredients dissolved in or included in the aqueous phase,

b) obtaining a hydrophobic phase in molten form,

C) the inclusion or dissolution of the encapsulated substance or a mixture of encapsulated substances in the aqueous phase or in the hydrophobic phase,

g) combining the aqueous phase with the hydrophobic phase and homogenizing or mixing the combined phases to obtain a water-in-oil emulsion,

e) encapsulating the aqueous phase in an emulsion and thereby converting the liquid aqueous phase into encapsulated water droplets, resulting in a dispersion comprising water droplets, and the active ingredient or active ingredients are dissolved in or included in the water droplets, and

f) processing the dispersion obtained in step e) to obtain microcapsules in which the encapsulated droplets of water are additionally encapsulated in a hardened hydrophobic matrix shell.

Another embodiment of the present invention relates to the use of the microcapsules of the present invention in the food / feed industry and for pharmaceutical or cosmetic purposes.

The present invention is based on the method of adding an encapsulated substance, for example a hydrocolloid or other suitable encapsulating substance or mixtures thereof, to the aqueous phase comprising the active ingredient (s), or to the hydrophobic phase in molten form to obtain an emulsion of the aqueous phase and the molten hydrophobic phase, followed by encapsulating the active ingredient (s) contained in an aqueous droplet or droplets in an emulsion. The encapsulation of the aqueous phase is carried out by gelation, crosslinking, fusion, agglomeration or by any other suitable means. This results in a dispersion in which the encapsulated water droplets are dispersed in a hydrophobic phase. The dispersion is cooled to a temperature below the melting or dropping point of the hydrophobic phase using a suitable method, which leads to the formation of microcapsules. Cooling can be carried out, for example, by spray cooling or fluidized bed cooling. Microcapsules include a number of encapsulated water droplets that further contain the active ingredient (s), and encapsulated water droplets are further encapsulated in, or using, a hardened hydrophobic matrix shell.

An advantage of the present invention is that the release of the active ingredient (s) from microcapsules can be controlled. The rate of release of a water-soluble active ingredient from a conventional microcapsule with a spray-cooled fat matrix is usually determined not by melting the fat matrix, but by the diffusion of water into the microcapsule and the subsequent movement of the active ingredient outside the capsule. The rate of release of the active ingredient from conventional spray-cooled, fat-matrix microcapsules is usually very high. Typically, the release rates of the active ingredients are such that, depending on the encapsulated active ingredient, about 80% is released within 15 minutes. The new microcapsules of the present invention have a much lower rate and / or prolonged release of active ingredients, since most of the active ingredients are released when the hardened hydrophobic matrix shell actually melts. The release of the active ingredients from the microcapsules of the present invention can be controlled and the release can be initiated in various ways, for example by heat treatment, for example by heating, such as in a microwave oven, or by freezing, by applying a load, or by any other suitable method. Isolation of the active ingredients from the microcapsules of the present invention may also be prolonged or may occur very slowly.

Another advantage of the microcapsules of the present invention is that the stability of the microcapsules is improved. Since the active ingredients are preferably dissolved in gelled or crosslinked encapsulated water droplets or included in droplets that are additionally encapsulated in or with the hardened hydrophobic matrix shell, the aqueous phase cannot move or vaporize into the matrix shell or outside the matrix shell .

The advantage of the microcapsules proposed in the present invention, compared with microcapsules of the prior art, for example microcapsules obtained in accordance with the cited publications of Lee and others, Dinsmore and others, Mofidi and others or Wong and others, is that for an additional encapsulation uses a hydrophobic phase, resulting in microcapsules in which the active ingredient (active ingredients) is first encapsulated inside water droplets and then further encapsulated in a hydrophobic phase.

These new improved characteristics of the microcapsules of the present invention allow the use of the microcapsules of the present invention in a wide variety of cases, for example, for various purposes in the food / feed industry and for pharmaceutical purposes.

Another advantage of the method proposed in the present invention is that it provides high performance at a fairly low cost.

In the present application, in one embodiment, the expression “encapsulated in a hardened hydrophobic matrix shell or with its help” can be considered to mean “encapsulated in a hardened hydrophobic matrix shell”. In another embodiment, the expression “encapsulated in, or using, a hardened hydrophobic matrix shell” can be considered meaning “encapsulated by a hardened hydrophobic matrix shell.”

For ease of reference, this and other embodiments of the present invention are discussed below in the sections with corresponding names. However, the data provided in each section is not necessarily limited to this particular section.

Brief Description of the Drawings

Below, the present invention will be described in more detail using preferred embodiments and examples.

The use of the designation "WOK" in the drawings and in the present description means an indication of the samples proposed in the present invention.

Figure 1 shows a graphical representation of the results of example 7. Comparison of the rates of release of calcium propionate, encapsulated and subjected to conventional spray cooling.

Figure 2 shows the image obtained by microscopy in transmitted light microcapsules proposed in the present invention.

Figure 3 shows the obtained using NSEM images of microcapsules proposed in the present invention.

Figure 4 shows a graph that compares the profiles of the allocation subjected to conventional spray cooling, proposed in the present invention and unencapsulated propionate Ca ²⁺ .

Figure 5 shows a graph that compares the allocation profiles of subjected to conventional spray cooling, proposed in the present invention and unencapsulated citric acid.

Figure 6 shows a graph that compares the allocation profiles for subjected to spray cooling and proposed in the present invention nisin at 30 ° C.

Figure 7 shows a graph in which the profiles of the selection of samples of betaine proposed in the present invention are compared.

Fig. 8 shows a microscopic image in transmitted light of the microcapsules of the present invention that have been frozen, which shows cracking of fat particles due to expansion of the internal aqueous phase during crystallization.

DETAILED DESCRIPTION OF THE INVENTION

The present invention relates to microcapsules that include a hardened hydrophobic matrix shell, an encapsulated aqueous droplet or droplets that are further encapsulated in or using a hardened hydrophobic membrane shell, and an active ingredient or active ingredients dissolved in or included in an encapsulated aqueous droplet or droplets in them.

Preferably, the aqueous droplet contains an encapsulating substance, such as a hydrocolloid, or other suitable encapsulating substance or a mixture thereof in a concentration suitable for it to be capable of gelation, crosslinking, fusion or agglomeration. Preferably, the encapsulated aqueous droplet is a gelled or crosslinked hydrocolloid droplet.

According to one embodiment of the present invention, the active ingredient or active ingredients are encapsulated twice in microcapsules. First, the active ingredient is dissolved in the aqueous phase containing the encapsulating substance, or included in the aqueous phase, such as a hydrocolloid or other suitable encapsulating substance or a mixture thereof, and the aqueous phase is encapsulated, for example, by gelation, crosslinking, fusion, agglomeration or any other suitable agents, and the resulting encapsulated aqueous droplet or droplets are further encapsulated in a hardened hydrophobic matrix shell.

Hydrophobic shell

The hydrophobic shell-matrix is selected based on the necessary properties of the microcapsule, for example, on the basis of the purpose of the microcapsules, storage temperature, etc. The preferred hydrophobic matrix shell should have a melting point in excess of 45 ° C so that it can be stored at room temperature, any hydrophobic substance can usually be used if the microcapsules are stored at a temperature lower than the melting temperature of the hydrophobic substance.

In this application, the molten form means that the hydrophobic phase is at the lowest temperature at which the hydrophobic phase is sufficiently fluid to drip in the form of droplets when tested using ASTM D 566 or D 265.

The hydrophobic matrix shell or hydrophobic phase may be selected from the group consisting of fats, oils, waxes, resins, emulsifiers, and mixtures thereof, which are preferably food grade. A preferred hydrophobic matrix shell or hydrophobic phase is selected from the group consisting of animal oils and fats, fully hydrogenated vegetable and animal oils, partially hydrogenated vegetable and animal oils, unsaturated, partially hydrogenated or fully hydrogenated fatty acids, unsaturated partially hydrogenated or fully hydrogenated monoglycerides and fatty acid diglycerides, unsaturated partially hydrogenated or fully hydrogenated monoglycerides and esterified diglycerides molecular weight acids, unsaturated partially hydrogenated or completely hydrogenated free fatty acids, other emulsifiers, animal waxes, vegetable waxes, mineral waxes, synthetic waxes, natural and synthetic resins, and mixtures thereof.

Animal oils and fats are, but are not limited to, beef tallow, mutton fat, sheep fat, lard or lard, spermaceti oil. Vegetable oils and preferably partially hydrogenated or fully hydrogenated vegetable oils are, but are not limited to, canola oil, cottonseed oil, peanut oil, corn oil, olive oil, soybean oil, sunflower oil, safflower oil, coconut oil, palm oil, linseed oil, tung oil and castor oil. Free fatty acids are, but are not limited to, stearic acid, palmitic acid and oleic acid. Other emulsifiers include, but are not limited to, polyglycerol esters, sorbitan fatty acid esters. Animal waxes are, but are not limited to, beeswax, lanolin, husk wax or Chinese waxworm wax. Vegetable waxes are, but are not limited to, carnauba, candelilla wax, wax wax or sugarcane wax. Mineral waxes are, but are not limited to, paraffin, microcrystalline petroleum wax, ozokerite, ceresin or mountain wax. Synthetic waxes are, but are not limited to, a low molecular weight polyolefin, polyol ethers, and synthetic waxes made using the Fischer-Tropsch technology. Natural resins are rosin, gum, shellac and zein.

Encapsulating substance

The encapsulated droplets of water in the microcapsules of the present invention contain an encapsulating substance, such as a hydrocolloid, which is any edible hydrocolloid or any other suitable encapsulating substance and which is capable of encapsulation by gelation (gelation), crosslinking, fusion, agglomeration or with using any other suitable means.

The encapsulating substance may be selected from the group consisting of hydrocolloids, shellac, zein, any synthetic or natural water-soluble polymers, any water-insoluble microparticles, such as silicon dioxide, titanium dioxide, granules of synthetic or natural food polymers and any water-insoluble solid particles whose particle size is substantially smaller than the size of water droplets in the aqueous phase and which are capable of agglomeration, and mixtures thereof.

Preferably, the hydrocolloid is selected from the group consisting of sodium alginate, gum arabic, gellan gum, starch, modified starch, guar gum, agar gum, pectin, amidated pectin, carrageenan, gelatin, chitosan, mesquite gum, cellulose, hyal cellulose acetate phthalate, hydroxypropyl methyl cellulose (HPMC), methyl cellulose, ethyl cellulose and carboxymethyl cellulose (CMC), methyl acrylic copolymers such as Eudragit®, plantain gum, tamarind gum, xanthan gum, ro gum gnar and a mixture of xanthan gum with carob gum, wheat protein, soy protein, sodium caseinate and any food protein and mixtures thereof.

In other embodiments, the encapsulating substance may be selected from any mixtures of oppositely charged hydrocolloids, such as gelatin / gum arabic, gelatin / CMC, any proteins / ionogenic hydrocolloids, any combination of hydrocolloids with solubility-reducing substances, such as salts, sugars, acids or bases, or sucrose acetate-isobutyrate (AIBS), damar gum, wood rosin glyceryl esters and mixtures thereof. In the case where fats, waxes or emulsifiers are used, they may differ from the hydrophobic matrix. Such mixtures are particularly preferred as encapsulating material for fusion.

The droplets of water in the microcapsules of the present invention are encapsulated. In this application, encapsulation means gelation, crosslinking, fusion, agglomeration or encapsulation using any other encapsulation means. Preferably, if the water droplets in the microcapsules of the present invention contain a hydrocolloid, and preferably if the water droplets form a gel or are crosslinked.

In a preferred embodiment of the present invention, the microcapsule includes a hardened hydrophobic matrix shell, transformed into a gel or a crosslinked droplet or droplets of an aqueous hydrocolloid encapsulated in a hardened hydrophobic matrix shell, and an active ingredient or active ingredients dissolved in a gelled or crosslinked droplet or drops hydrocolloid or included therein.

The gelled hydrocolloids typically have a gelation temperature in excess of room temperature. Examples of gelled hydrocolloids include carrageenan, gelatin, guar gum, agar gum, starch, modified starch and a mixture of xanthan gum with locust bean gum, a mixture of carrageenan with locust bean gum, a mixture of any gelling hydrocolloids with other non-gelling hydrocolloids.

The crosslinking of hydrocolloids is carried out using crosslinking agents or using various techniques. If the hydrocolloid is a protein or polysaccharide containing amino groups such as chitosan, acacia gum, gum arabic or mesquite gum, it can be crosslinked with dialdehydes such as glutaraldehyde. If the hydrocolloid is a polysaccharide, such as sodium alginate, gellan gum or pectin, it can be crosslinked using multivalent ions, such as calcium or magnesium ions. Crosslinking can also be done by other means, such as heating, pH adjustment, pressure application or enzymatic crosslinking. Proteins, for example, can be crosslinked by applying a high pressure to the protein, preferably from 2 to 200 bar or from 5 to 200 bar, and / or by heating the protein to a temperature higher than the protein denaturation temperature. The heating temperature depends on the hydrocolloid to be crosslinked. Enzymatic crosslinking of proteins can be performed, for example, using transglutamidase. Depending on the hydrocolloid used, one skilled in the art may decide which gelling or crosslinking method to use.

The droplets of water in the microcapsules of the present invention can be encapsulated by fusion. The fusion of an encapsulating substance, such as a hydrocolloid, is carried out using any suitable fusion method. The merger can be performed, for example, by adding salt (s), sugar (sugars) or other additives that lead to phase separation of the encapsulating substance, such as hydrocolloid (s). The fusion can also be performed by heating, cooling, changing the pH by adding an acid or base, which lead to phase separation of the encapsulating substance (s), such as hydrocolloid (s). The precipitation of the merged phase around the aqueous phase and at the interface between the hydrophobic matrix and the aqueous phase is spontaneous and is caused by surface tension forces. The merged layer can then be crosslinked or cured by any suitable means known to those skilled in the art of fusion.

Encapsulating substances suitable for fusion are selected from the group consisting of shellac, zein, any synthetic or natural hydrophobic polymers, fats, emulsifiers, waxes, any mixtures of oppositely charged hydrocolloids, such as gelatin / gum arabic, gelatin / CMC, any proteins / ionogenic hydrocolloids , combinations of hydrocolloids with solubility-reducing substances, such as salts, sugars, acids or bases, or sucrose acetate-isobutyrate (AIBS), damar gum, wood rosin glyceryl esters, and mixtures thereof.

Agglomeration in this application means that the microparticles coalesce with each other to form a porous or non-porous film. Agglomeration of the encapsulating substance is carried out by adding an appropriate amount of solid insoluble microparticles, the particle size of which is significantly smaller than the size of water droplets in the aqueous phase. Microparticles are, for example, silicon dioxide, titanium dioxide, granules of synthetic or natural food polymers, or any water-insoluble solid particles whose particle size is substantially smaller than the size of water droplets in the aqueous phase. The microparticles are then allowed to spontaneously precipitate around the aqueous phase by heating the microparticles to a temperature above their agglomeration temperature or glass transition temperature, and thereby a continuous film of microparticles is formed.

Active ingredient

The active ingredient or a mixture of active ingredients (which can be dissolved in water droplets or included in gelled, cross-linked, fused or agglomerated water droplets) can be any ingredient, preferably a hydrophilic food or pharmaceutical ingredient, and selected according to the purpose of the microcapsules . The active ingredient may be, for example, an inorganic or organic salt or acid, such as calcium propionate, propionic acid, sorbic acid, calcium sorbate, ascorbic acid, sodium chloride, fumaric acid, potassium sorbate, citric acid or sodium bicarbonate. The active ingredient may also be a flavoring agent, such as a pizza flavoring or coffee flavoring, or the active ingredient may be a bactericidal agent or preservative, such as a bacteriocin (e.g. nisin or pediocin), natamycin, a nutrient, or a vitamin, such as vitamin C or betaine. A mixture of any of the above ingredients can also be used in microcapsules.

Preferably, the active ingredient is selected from the group of flavors, flavoring agents, nutrients, vitamins, preservatives, disintegrants, microorganisms, acidifiers, antioxidants, colorants, enzymes, gases, thickeners and any other pharmaceutical ingredients. Suitable pharmaceutically active ingredients include antibiotics, antimicrobials, anti-inflammatory drugs, analgesics, sedatives, hypnotics, anxiolytics, antihistamines, antiarrhythmic drugs, antihypertensive drugs, drugs for treating parkinsonism, hormones.

The microcapsules of the present invention may include from about 1 to 100 water droplets encapsulated in a hydrophobic matrix shell, preferably from 5 to 50 water droplets. The size of the microcapsule is from about 40 to 800 microns, preferably from 100 to 150 microns. The size of the water droplet may be from about 0.1 to 20 microns, preferably from 1 to 5 microns. The number and size of water droplets encapsulated in the hardened hydrophobic shell-matrix of the microcapsule may vary depending on the purpose of the microcapsules. The size of the microcapsules proposed in the present invention may also vary depending on the purpose.

Way

The present invention also relates to a new method for producing the microcapsules of the present invention, which method comprises the steps of

a) obtaining an aqueous phase comprising the active ingredient or active ingredients dissolved in or included in the aqueous phase,

b) obtaining a hydrophobic phase in molten form,

C) the inclusion or dissolution of the encapsulated substance or a mixture of encapsulated substances in the aqueous phase or in the hydrophobic phase,

g) combining the aqueous phase with the hydrophobic phase and homogenizing or mixing the combined phases to obtain a water-in-oil emulsion,

e) encapsulating the aqueous phase in an emulsion and thereby converting the liquid aqueous phase into encapsulated water droplets, resulting in a dispersion comprising water droplets, and the active ingredient or active ingredients are dissolved in or included in the water droplets, and

f) processing the dispersion obtained in step e) to obtain microcapsules, in which the encapsulated droplets of water are additionally encapsulated in a hardened hydrophobic matrix shell or with it.

As used herein, the aqueous phase means water or a mixture of water with any other water miscible solvent, such as ethanol, ethylene glycol or glycerin. The aqueous phase may also include additives, such as carbohydrates, such as monosaccharides or oligosaccharides, designed to change the properties of the hydrocolloid gel, inorganic salts, designed to change the properties of protein gels, preservatives, designed to prevent decomposition of microcapsules by bacteria and fungi, or emulsifiers as technological additives, sorbitan tristearate or other emulsifiers as crystalline modifiers, hydrophobic natural or synthetic polymers intended To change the mechanical properties of the matrix, plasticizers, preservatives, intended to avoid the destruction of microcapsules.

The combination of the aqueous phase with the hydrophobic phase is preferably carried out by stirring.

The homogenization in step d) is preferably carried out by mixing with high shear or mixing on a production line.

An encapsulating substance is a hydrocolloid, a mixture of hydrocolloids, or any other encapsulating substance or a mixture thereof.

The encapsulation in step e) can be carried out by gelation, crosslinking, fusion, agglomeration, or any other suitable encapsulation means which result in encapsulation of the aqueous phase comprising the active ingredient or active ingredients.

Encapsulation using gelation (gelation) in step e) can be carried out by cooling the emulsion. Encapsulating agents suitable for use as gelling encapsulating substances may be selected from the group consisting of carrageenan, gelatin, starch, modified starch, agar gum, guar gum, a mixture of xanthan gum with locust bean gum and a mixture of any gelling hydrocolloids.

Encapsulation using crosslinking in step e) is carried out using crosslinking agents or in various ways, such as heating, applying pressure, by enzymatic crosslinking. Crosslinking can be carried out by heating the emulsion to a temperature of 60 to 120 ° C. Crosslinking can also be carried out by exposing the emulsion to a medium having such a pH value that leads to the denaturation of the hydrocolloids. The pH value is usually from 2 to 12. Crosslinking can also be carried out by applying a pressure of 2 to 200 bar to the emulsion. The crosslinking agent may be selected from the group consisting of dialdehydes such as glutaraldehyde, divalent ions such as calcium or magnesium ions, enzymes and other crosslinking compounds such as irridoids.

Encapsulation by gelation or crosslinking leads to the formation of microcapsules in which the active ingredient is encapsulated in jelly-like droplets formed from a hydrocolloid network, and they are then further encapsulated in a hydrophobic matrix shell.

Encapsulation by fusion in step e) can be carried out by reducing the solubility of an encapsulating substance, such as a hydrocolloid, so that a fusion phase forms and this fusion phase then itself precipitates around the aqueous phase. The aqueous phase in the emulsion is encapsulated to form a dispersion containing encapsulated solid drops of water.

The merger can be carried out either using a hydrophilic encapsulating substance, or using a hydrophobic encapsulating substance. If a hydrophilic encapsulating substance is used, then the hydrophilic encapsulating substance is first dissolved in the aqueous phase and a solubility reduction technique such as changing the temperature or pH or the use of additives is usually used to remove the hydrophilic encapsulating substance from the aqueous phase, and then said encapsulating substance is deposited at the interface between the hydrophilic phase in molten form and the aqueous phase. The encapsulating substance is then optionally cured by changing the temperature or pH or adding additives. If a hydrophobic encapsulating substance is used, the hydrophobic encapsulating substance is first dissolved in the hydrophobic phase in molten form, and a solubility reduction technique such as a temperature change or the addition of additives can be used to remove the hydrophobic encapsulating substance from the hydrophobic phase. After this, it is possible to carry out the deposition of the specified encapsulating substance at the interface between the hydrophobic phase and the aqueous phase.

Encapsulation by agglomeration in step e) can be carried out by adding an appropriate amount of solid insoluble microparticles, such as silicon dioxide, titanium dioxide, granules of synthetic or natural food polymers, or any water-insoluble solid particles whose particle size is substantially smaller than the size of aqueous droplets in aqueous phase, which microparticles are capable of agglomeration in the emulsion. Then the microparticles are allowed to spontaneously precipitate around the aqueous phase at the interface between the hydrophobic phase and the aqueous phase, and the microparticles are heated to a temperature exceeding their agglomeration temperature or their glass transition temperature. The microparticles coalesce with each other to form a continuous film. Thus, a dispersion of water droplets encapsulated with a thin film of agglomerated microparticles in a hydrophobic matrix shell is obtained.

Encapsulating substances suitable for encapsulation by agglomeration of substances can be selected from the group comprising any water-insoluble microparticles, such as silicon dioxide, titanium dioxide, granules of synthetic or natural food polymers and any water-insoluble solid particles, the particle size of which is significantly smaller the size of aqueous droplets in the aqueous phase in a hydrophobic matrix.

Encapsulation by fusion or agglomeration results in microcapsules in which a thin coating of the encapsulating substance is deposited around water droplets comprising the active ingredient (s) and the droplet or droplets are further encapsulated in or using the hardened hydrophobic matrix shell.

The dispersion of the combined solution in step e) is carried out by any suitable method or means that reduce the solubility of the dissolved encapsulating material, which leads to the precipitation of the encapsulating substance around the aqueous phase. It is preferable to carry out stage d) by changing the temperature, lowering or raising the temperature, or by adding additives.

The treatment in step e) is carried out in any suitable manner that leads to the solidification of the hydrophobic phase to form a hydrophobic matrix shell and to form a microcapsule. The treatment is preferably carried out by spray cooling or fluidized bed cooling. The treatment is more preferably carried out by spray cooling.

The hydrophobic phase is selected based on the necessary properties of the microcapsule, for example, based on the purpose of the microcapsule, storage temperature, and the like. The preferred hydrophobic matrix shell should have a melting point in excess of 45 ° C so that it can be stored at room temperature.

The present invention preferably relates to a method, which includes stages

a) obtaining an aqueous phase comprising a hydrocolloid or a mixture of a hydrocolloid and an active ingredient or active ingredients,

b) obtaining a hydrophobic phase in molten form,

C) combining the aqueous phase obtained in stage a) with a hydrophobic matrix obtained in stage b), and homogenizing the combined solution to obtain an emulsion,

d) gelation or crosslinking of the hydrocolloids in an emulsion, resulting in a dispersion comprising gelled or crosslinked droplets of the hydrocolloid, and the active ingredient or active ingredients are dissolved in or incorporated into the gelled or crosslinked droplets of the hydrocolloid, and

d) cooling the dispersion obtained in step d) by spray cooling or fluidized bed cooling to form microcapsules in which gelled or crosslinked hydrocolloid droplets are encapsulated in a hardened hydrophobic matrix shell.

The combination of the aqueous phase obtained in stage a) with the hydrophobic phase obtained in stage b) is preferably carried out by stirring.

The homogenization in step c) is preferably carried out by mixing with high shear or mixing on the production line.

The hydrocolloid for use in the present invention may be any edible hydrocolloid, preferably is water soluble and capable of gelation and / or crosslinking.

The hydrocolloid contained in the emulsion is preferably gel or crosslinked. The hydrocolloid (s) to be gelled have a gelation temperature in excess of the storage temperature. Examples of gelling hydrocolloids include carrageenan, gelatin, starch, modified starch, agar gum, guar gum and a mixture of xanthan gum with locust bean gum or a mixture of any gelling hydrocolloids with any other non-gelling hydrocolloids. The gelation of the hydrocolloids in the emulsion can be carried out by cooling the emulsion before or during the cooling step. If gelling of the hydrocolloid is carried out during cooling, the emulsion is cooled after its formation. If gelation of the hydrocolloid is carried out before spray cooling, a dispersion is formed which includes gel droplets of the hydrocolloid, and then this dispersion is cooled to form microcapsules.

The crosslinking agent may be selected from the group consisting of dialdehydes such as glutaraldehyde, divalent ions such as calcium or magnesium ions, and other crosslinking compounds such as irridoids.

The dispersion is preferably cooled by spray cooling in a spray tower, or by cooling in a fluidized bed in a fluidized bed apparatus. During spray cooling, the hydrophobic matrix, which in the dispersion is in molten form, cools so that it solidifies in the form of small particles encapsulating droplets of the hydrocolloid. The spray tower may use gas at room temperature or chilled gas. Preferably, the gas or cooling gas is air. The temperature of the cooling gas may be from −270 to 50 ° C., preferably from −50 to 40 ° C., and more preferably from −20 to 20 ° C.

The characteristics of the microcapsules can be changed by changing the technological parameters of the above methods. For example, plasticizers can be added to the hydrophobic matrix to increase elasticity and change the mechanical characteristics of the outer shell, and lipase enzymes can be added to the aqueous phase to change the rate of excretion.

One microcapsule obtained by the method proposed in the present invention may include from about 1 to 100 water droplets included in a hydrophobic membrane shell, preferably from 5 to 50 water droplets. The size of the microcapsule is from about 40 to 800 microns, preferably from 100 to 150 microns. The size of the water droplet may be from about 0.1 to 20 microns, preferably from 1 to 5 microns.

The present invention also relates to the use of the microcapsules of the present invention. The microcapsules described above can be used in a variety of cases in the food industry and for pharmaceutical purposes.

The microcapsules of the present invention can be used in a wide variety of cases, depending on the properties of the microcapsules, the active ingredient or a mixture thereof, the hydrocolloid, the hydrophobic matrix and the size of the microcapsules. The present invention provides controlled release of the active ingredients from microcapsules. The release of the active ingredients from the microcapsules can be controlled by initiating the release in various ways, for example by heating, by heating in a microwave oven or by any other suitable method. Isolation of the active ingredients from the microcapsules of the present invention can also occur very slowly. Isolation of the active ingredient also occurs when microcapsules are frozen. Freezing leads to the expansion of the aqueous phase, which causes cracking of the outer hydrophobic matrix. After thawing, the active ingredient is rapidly released from the microcapsule.

For example, when baking using the microcapsules of the present invention, it is possible to provide a delayed release of an anti-molding agent. This is important to prevent inhibition of the necessary activity of baker's yeast. If nisin or natamycin are used as active ingredients, then the increased thermal stability of pasteurized and heat-treated food products is ensured. Slowed release of sodium chloride is also very important, for example, for cheeses to avoid harmful interactions with starter cultures. Using the microcapsules proposed in the present invention, it is possible to ensure thermal stability of vitamin C during baking / manufacturing of confectionery products.

Betaine is used in feeds to supplement the nutritional value of fish and shrimp feeds. However, since it is very hygroscopic and highly soluble in water, it is pipe-like to ensure a constant release for fish over a long period of time, since betaine is leached from the feed pellets before the animals eat them.

Encapsulation in accordance with the present invention can prevent premature dissolution, which ensures the effective provision of betaine to fish. Spray cooling cannot lead to the formation of microcapsules that retain their contents in the aquatic environment for more than 10-15 minutes, which is not long enough for use in fish feed. These difficulties are overcome with betaine encapsulated in accordance with the present invention.

The present invention relates to the use of microcapsules as flavorings, bactericidal agents, preservatives and agents for slow, controlled and / or prolonged release of the active ingredient (s). The microcapsules of the present invention can be used for a wide variety of pharmaceutical purposes when slow, controlled and / or prolonged release of a pharmaceutically active ingredient is required. Such uses include, for example, depot tablets and transdermal administration systems.

The controlled release of flavorings in food products such as pastries, pizza, instant coffee, tea bags is provided by the microcapsules of the present invention containing flavorings as an active ingredient. Encapsulated flavors are held in the product until they are exposed to heat and / or load to isolate the flavors. Heating can be performed, for example, using a microwave oven, a conventional oven or hot water. The load can be created, for example, using processing conditions or chewing.

Using the microcapsules of the present invention, a slow release of bacteriocin is provided, for example, in processed meat products or drinks, such as orange juice. If a preservative is used as the active ingredient in water droplets in the microcapsules of the present invention, the preservative is slowly released in the product as it naturally decomposes. This effectively prevents the growth of fungi and other unwanted microorganisms for a longer period of time than when using an unencapsulated preservative, which ensures a longer shelf life of the food product. The coating can also provide thermal stability of bacteriocin and preservatives, so that they can withstand heat treatment and harsh processing conditions, but maintain activity during storage of the processed product.

The microcapsules proposed in the present invention provide a delayed release of salt in the manufacture of cheese, which allows a 1-stage process instead of a 2-stage process. Slow release of salt ensures the proper functioning of the starter culture at the beginning, since it does not experience the harmful effects of salt. After fermentation is complete, salt is released. In a typical process, salt is added after fermentation is completed by immersing the cheese in brine for a long time.

Using the microcapsules of the present invention, the delayed release of antimicrobial agents during baking is provided. Preservatives are widely used to extend the shelf life of bread and other bakery products, but due to the harmful effects on the effectiveness of the yeast. Slow release allows for more efficient use of yeast, as well as preservation after isolation of the active ingredient during baking. As an added benefit, propionic acid, which is more active than its calcium salt, but which is more difficult to use due to its high acidity and liquid form, can be converted into a stable powder that is easy to use.

The pharmaceutically active ingredients encapsulated in accordance with the present invention provide a slow, controlled and / or prolonged release of the active ingredient over time, for example, in depot tablets, in a cheaper way than is currently done (using a coating applied in fluidized bed). Encapsulation in accordance with the present invention also ensures the stability of the pharmaceutically active ingredients in the gastrointestinal tract (at low pH), which ensures their subsequent isolation in the intestinal tract, where most pharmaceutically active ingredients are actually absorbed. Examples of suitable pharmaceutically active ingredients include antibiotics, antimicrobials, anti-inflammatory drugs, analgesics, sedatives, hypnotics, anxiolytics, antihistamines, antiarrhythmic drugs, antihypertensive drugs, drugs for treating parkinsonism and hormones.

Other ingredients and possible uses are as follows:

Betaine - feed substances

Nisin - Bakery

Natamycin - Bakery

Ascorbic acid - bakery, rolled dough

Sorbic Acid - Bakery

Flavors - frozen pizza, drinks, cereal dishes

Propionic Acid - Bakery

Nisin - shell for sausages, vinaigrette

Citric, Fumaric Acid - Bakery, Tortillas

Water - cooking low-calorie fat for spreading on bread, baking

Sodium chloride is used as a flavoring agent in cheese and is usually added at the end of ripening by immersing the entire cheese head in brine. It takes a long time and is expensive. Preliminary studies have shown that encapsulated sodium chloride can be added to milk at the beginning of fermentation and slow release reduces the harmful effects of salt on the culture of the starter culture, but provides adequate taste at the end of ripening.

Ascorbic acid is used in puff pastry to strengthen the gluten net during oxidative protein crosslinking. Crosslinking and densification of the dough matrix should occur after the kneading / lamination step of the dough so as not to degrade the structure of the finished product. Premature stitching and compaction results in a test that is harder to process and that is unattractive in appearance. The slow release of ascorbic acid due to encapsulation provides easier processing of the dough before compaction. Compared to spray cooling, encapsulation has the advantage that it more effectively delays the release and the flow of already dissolved ascorbic acid provides a quick distribution of the acid after its release.

Encapsulating water may also be beneficial. According to the present invention, it is possible to firmly encapsulate water. Using encapsulated water, you can prepare Ciabatta bread with large and uneven pores: during baking, droplets of water are released, during the evaporation of which large pores are formed. A non-spatter, low-fat spreading paste can be obtained if the water used in the emulsion is encapsulated and it is less likely to evaporate when heated.

Additional components

An encapsulated antimicrobial agent, in addition to the core of the active ingredient and the capsule of the encapsulating material, may contain one or more components. These one or more of the components can be encapsulated or not encapsulated in the shell or using the shell together with the active ingredient. In other words, additional components can be encapsulated in the shell or using the shell together with the active ingredient, or they can be located outside the shell. When one or more additional components are used, the above combination is formed (one component may be inside the shell and the other outside the shell).

Typically, an encapsulated antimicrobial agent is not incorporated into the food product by itself. So, in one embodiment, the encapsulated antimicrobial agent is introduced into the food product in a carrier. Preferably, the carrier is or includes water.

The density of the encapsulated antimicrobial agent should be close to the density of the carrier (such as brine) in order to prevent the encapsulated antimicrobial agent from separating or precipitating and thereby prevent the uneven distribution of the encapsulated antimicrobial agent during application or kneading. Thus, in a preferred embodiment, the carrier and the encapsulated antimicrobial agent have substantially the same density.

The closeness of the densities of the carrier and the encapsulated antimicrobial agent can be ensured by careful selection of the carrier and the encapsulated antimicrobial agent. Alternatively, it can be provided by modifying the encapsulated antimicrobial agent so that it has a density very close to that of the carrier, or by modifying the carrier such that it has a density very close to the density of the encapsulated antimicrobial agent. The encapsulated antimicrobial agent can be modified by mixing the encapsulated antimicrobial agent with an oil, such as brominated oil. The carrier can be modified by the inclusion of additional components, such as xanthan gum.

The carrier may contain one or more additional components. However, in some embodiments, the carrier does not contain additional components or does not contain additional components that significantly affect the properties of the composition.

In one preferred embodiment, the carrier further comprises an emulsifier. Preferably, the emulsifier is selected from the group consisting of polyoxyethylene sorbitan esters (E432-E436), also known as polysorbates (e.g., Tween 80, Tween 20), monoglycerides, diglycerides, acetic acid esters of mono-dihydricerides, tartaric acid esters of monoglycerides citric acid mono-digdicerides.

The encapsulated antimicrobial agent may contain one or more additional components. However, in some embodiments, the encapsulated antimicrobial agent does not contain additional components or does not contain additional components that significantly affect the properties of the composition.

In one preferred embodiment, the encapsulated antimicrobial agent further comprises an extract obtained or obtained from a plant of the Labiatae family. Optional in this embodiment, and preferably, if the antimicrobial agent contains nisin, the composition comprises carvacrol in an amount of less than 0.075 wt.% In terms of the composition, and carvon in an amount of less than 15 wt.% In terms of the composition. Compositions comprising an antimicrobial agent and an extract obtained or obtained from a plant of the Labiatae family are discussed in our UK patent application No. 0323335.0. All provisions of GB 0323335.0 are applicable to the system proposed in the present invention.

In this embodiment, it is preferable that the extract obtained or obtained from a plant of the Labiatae family not be encapsulated in the shell or with it together with an antimicrobial agent.

In one preferred embodiment, the extract contains carvacrol in an amount of less than 0.075 wt.% In terms of the composition, preferably in an amount of less than 0.04 wt.% In terms of the composition, more preferably in an amount of less than 0.02 wt. .% in terms of composition.

In one preferred embodiment, the extract contains carvone in an amount of less than 0.075 wt.% In terms of the composition, preferably in an amount of less than 0.04 wt.% In terms of the composition, more preferably in an amount of less than 0.02 wt. .% in terms of composition.

In one preferred embodiment, the extract contains thymol in an amount of less than 0.1 wt.% In terms of the composition, preferably in an amount of less than 0.075 wt.% In terms of the composition, more preferably in an amount of less than 0.0 wt. .% in terms of composition.

In one embodiment, the applicable extract is obtained from a plant of the Labiatae family.

One of ordinary skill in the art should understand that the term "extract" or "extracts" means any component of a plant that can be isolated from a whole plant.

In one embodiment, the extract used in the present invention is obtained from a plant of the Labiatae family. One skilled in the art should understand that an extract obtained from a plant can be obtained from a plant or can be isolated from a plant, identified and then obtained from an alternative source, for example, by chemical synthesis or enzymatic production. For example, the extract can be obtained using eukaryotic or pro-eukaryotic fermentation, using genetic exposure. The authors of this application have found that the products contained in plants of the Labiatae family can synergistically increase the activity of an antimicrobial agent, preferably bacteriocin. These products can be obtained from any source and are included in the scope of the present invention.

The present invention includes the use of a combination of a bacteriocin, such as nisin, and a plant of the Labiatae family, such as rosemary (Rosmarinus officinalis) or sage (Salvia officinalis), which together provide improved destruction of gram-positive bacteria in the food system. The synergistic extracts of the present invention preferably relate to extracts of plants of the Labiatae family that are subjected to selective extraction (“deodorized extracts”) to increase the content of phenolic diterpene (such as carnosol and carnosic acid), the content of phenolic triterpene (such as ursolic acid, betulinic acid and oleanolic acid) or rosmarinic acid content. These deodorized extracts may have a high phenolic diterpen content (for example, more than 3.5 wt.%) And a low content (less than 1 wt.%) Of flavoring compounds from the number of vegetable essential oils and oleosol, which are used as fragrances or perfumes. Essential oils are usually extracted by conventional steam distillation of the plant material.

In one preferred embodiment, the extract is a deodorized extract. Preferably, the (deodorized) extract contains from 1.0 to 70 wt.% Phenolic diterpenes, preferably from 3.5 to 70 wt.% Phenolic diterpenes and less than 1 wt.% Essential oil.

In one preferred embodiment, the extract is selected from the group consisting of phenolic diterpenes, phenolic triterpenes and rosmarinic acid.

In one preferred embodiment, the extract is or includes phenolic diterpene. Preferably, the phenolic diterpene is selected from the group consisting of carnosic acid, carnosol, methyl carnosic acid, and mixtures thereof. Preferably, the phenolic diterpene is selected from the group consisting of carnosic acid and carnosol.

In one preferred embodiment, the extract contains phenolic diterpenes in an amount greater than 1.0 wt.%, Calculated on the composition, preferably in an amount greater than 2.0 wt.%, Calculated on the composition, more preferably in an amount greater than 3, 0 wt.%, In terms of the composition, even more preferably in an amount exceeding 3.5 wt.%, In terms of the composition.

In one particularly preferred embodiment, the extract contains one or more phenolic triterpenes. Preferably, the phenolic triterpenes are selected from the group consisting of betulinic acid, oleanolic acid and ursolic acid.

In one preferred embodiment, the extract is or includes phenolic triterpene. Preferably, the phenolic triterpene is selected from the group consisting of betulinic acid, oleanolic acid and ursolic acid.

In one preferred embodiment, the extract is or includes rosmarinic acid.

In one preferred embodiment, a plant of the Labiatae family is selected from the group consisting of rosemary, sage, oregano, marjoram, mint, lemon balm, savory and thyme. In one preferred embodiment, a plant of the Labiatae family is selected from the group consisting of rosemary, sage, oregano, marjoram, mint, lemon balm and savory. It should be understood that these names include all types and varieties of plants known under the indicated names.

In one preferred embodiment, a plant of the Labiatae family is selected from the group consisting of rosemary (Rosmarinus officinalis L.), sage (Salvia officinalis L.) oregano (Origanum vulgare L.), marjoram (Origanum marjorana L.), mint (Mentha spp.) , melissa (Melissa officinalis L.), savory (Satureia hortensis), thyme (Thymus vulgaris L.).

In one preferred embodiment, a plant of the Labiatae family is selected from the group consisting of rosemary (Rosmarinus officinalis L.), sage (Salvia officinalis L.) oregano (Origanum vulgare L.), marjoram (Origanum marjorana L.), mint (Mentha spp.) , lemon balm (Melissa officinalis L.) and savory (Satureia hortensis).

In one preferred embodiment, the plant of the Labiatae family is rosemary.

In one preferred embodiment, the extract contains flavoring agents and / or essential oils in an amount of less than 1% by weight, based on the extract. In one preferred embodiment, the extract contains flavoring agents and / or essential oils in an amount of less than 1% by weight, based on the composition.

Typically, flavoring agents and / or essential oils are camphor, verbenone, borneol, and alpha terpineol.

In one preferred embodiment, the total amount of camphor contained in the extract is less than 1 wt.% (Preferably less than 0.2 wt.%, More preferably less than 0.15 wt.%, More preferably less than 0.1 wt.%) in terms of extract.

In one preferred embodiment, the total amount of verbenone contained in the extract is less than 1 wt.% (Preferably less than 0.2 wt.%, More preferably less than 0.15 wt.%, More preferably less than 0.1 wt.%) in terms of extract.

In one preferred embodiment, the total amount of borneol contained in the extract is less than 1 wt.% (Preferably less than 0.2 wt.%, More preferably less than 0.15 wt.%, More preferably less than 0.1 wt.%) in terms of extract.

In one preferred embodiment, the total amount of alpha terpineol contained in the extract is less than 1 wt.% (Preferably less than 0.2 wt.%, More preferably less than 0.15 wt.%, More preferably less than 0.1 wt.% ) in terms of extract.

In one preferred embodiment, the total amount of camphor, verbenone, borneol and alpha-terpineol contained in the extract is less than 1 wt.% (Preferably less than 0.2 wt.%, More preferably less than 0.15 wt.%, Even more preferably less than 0.1 wt.%) in terms of extract.

In one preferred embodiment, the encapsulated antimicrobial agent further comprises a chelating agent. Preferably, the chelating agent is selected from the group consisting of EDTA (ethylenediaminetetraacetic acid), citric acid, monophosphates, diphosphates, tri- and polyphosphates.

Other suitable chelating agents are described in US 5,573,801 and include carboxylic acids, polybasic carboxylic acids, amino acids and phosphates. In particular, the following compounds and their salts may be applicable:

acetic acid, adenine, adipic acid, ADP (adenosine diphosphate), alanine, B-alanine, albumin, arginine, ascorbic acid, asparagine, aspartic acid, ATP (adenosine triphosphate), benzoic acid, n-butyric acid, casein, citraconic acid, acid, cysteine, dehydroacetic acid, desferri-ferrihrizine, desferri-ferrihrom, desferri-ferrioxamine E, 3,4-dihydroxybenzoic acid, diethylenetriaminepentaacetic acid (DTTA), dimethylglyoxime, O, O-dimethylpurpuyupuraya acid, fumurpuraya acid, O-dimethylpurfuyuruypuruyaluypuruypuruyaluypuruyuruyaluypuruyuruyaluypuruyuruyaluypuruyuruyaluypuruyuruyaluypuruypurinaya acid; Uline, gluconic acid, glutamic acid, glutaric acid, glycine, glycolic acid, glycylglycine, glycyl sarcosine, guanosine, histamine, histidine, 3-hydroxyflavone, inosine, inosine triphosphate, iron-free ferrihrom, isovaleric acid, lactic acid, itaconic acid, itaconic acid, itaconic acid , leucine, lysine, maleic acid, malic acid, methionine, methyl salicylate, nitrilotriacetic acid (NTK), ornithine, orthophosphate, oxalic acid, oxystearin, B-phenylalanine, phosphoric acid, phytate, pimelic acid, trimeth luksusnaya acid, polyphosphate, proline, propionic acid, purine, pyrophosphate, pyruvic acid, riboflavin, salicylaldehyde, sarcosine, serine, sorbitol, succinic acid, tartaric acid, tetrametafosfat thiosulfate, threonine, trimetaphosphate, triphosphate, tryptophan, uridine diphosphate, uridine triphosphate, n-valerianic acid, valine and xanthosine.

Many of the above complexing agents are useful in treating foods in the form of salts, which are usually alkali metal and alkaline earth metal salts such as sodium, potassium or calcium salts or quaternary ammonium salts. Multivalent complexing agents can be successfully used to control pH or to selectively introduce or remove metal ions, for example, in food coatings. Further information on chelating agents is given in T.E. Furia (eds.), CRC Handbook of Food Additives, 2nd ed., Pp. 271-294 (1972, Chemical Rubber Co.) and MSPeterson and A.M. .Johnson (eds.). Encyclopaedia of Food Science, cc.694-699 (1978, AVI Publishing Company, Inc.), and both of these publications are incorporated herein by reference.

The term “chelating agent” is defined as organic or inorganic compounds capable of forming coordination complexes with metals. In addition, when used in the present invention, the term "chelating agent" includes compounds that form molecular inclusion compounds, such as cyclodextrin. The chelating agent may be inorganic or organic, but organic is preferred.

A preferred chelating agent is non-toxic to mammals and includes aminopolycarboxylic acids and their salts, such as ethylenediaminetetraacetic acid (EDTA) and its salts (preferably its di- and trisodium salts), and hydroxycarboxylic acids and their salts, such as citric acid. However, a chelating agent other than citric acid and citrate, such as acetic acid, lactic acid, tartaric acid, and salts thereof, is believed to be useful in the present invention.

As noted above, the term “chelating agent” is defined and used in the present invention as a synonym for a complexing agent and is defined as including and forming compounds comprising molecular inclusion compounds such as cyclodextrin. Cyclodextrins are cyclic carbohydrate molecules containing 6, 7 or 8 monomeric glucose units arranged in the form of a toroidal ring and are called alpha, beta and gamma cyclodextrins, respectively. When used in the present invention, cyclodextrin means unmodified and modified cyclodextrin monomers and polymers. Cyclodextrins incorporating molecular compounds sold by American Maize-Products of Hammond, Ind. Cyclodextrins are also described in Chapter 11, entitled "Industrial Applications of Cyclodextrin," written by J. Szejtli, cc. 313-390, in Inclusion Compounds , vol. III (Academic Press, 1984), and this chapter is incorporated into the present invention by reference.

Preferably, the chelating agent enhances the bactericidal activity and / or the bactericidal spectrum of the bactericidal effect. More preferably, the chelating agent enhances the bactericidal activity and / or spectrum of bactericidal action of bacteriocin in relation to gram-negative bacteria and other microorganisms.

According to the invention, we have found that the use of a chelating agent is particularly effective in terms of enhancing the bactericidal activity and / or the bactericidal spectrum of the bacteriocin used. This enhancement is possible regardless of the method of isolation of the encapsulated antimicrobial agent and the nature of the shell of the encapsulated antimicrobial agent.

Examples

Example 1. Encapsulation of flavoring with pizza flavor.

First, a solution of 1.5 g of κ-carrageenan in 110 ml of water at 85 ° C is prepared. To it are added 110 ml of pre-warmed (80 ° C) liquid water-soluble pizza flavor. The resulting mixture was thoroughly mixed. Then a mixture of 200 g of plant triglyceride (GRINDSTED® PS 101, mp 58 ° C) and 11 g of acetylated emulsifier (Acetem 50 00) is melted at 85 ° C in a water bath. The molten fat mixture is maintained in a homogenized state (Silverson mixer, 8000 rpm) and the aqueous mixture is slowly added. Homogenization is continued for 5 minutes after the addition of the entire aqueous mixture, and then, with continuous stirring, a solution of 0.45 g of polysorbate 80 in 15 ml of water is added. Immediately after this, the low-viscosity water-in-oil emulsion is spray-cooled in a Niro spray tower under the following conditions: inlet air temperature 10 ° C, outlet air temperature 28 ° C, spray drum rotation speed of 10,000 rpm. A pizza flavor bulk powder is obtained.

A 6-inch diameter frozen pizza sample is sprinkled with 1.5 g of flavoring powder and baked in the microwave for 2 minutes at medium and high radiation intensities. After being extracted from the microwave, flavored pizza samples clearly have a more intense pizza flavor than control pizza samples.

Example 2. Encapsulation of a coffee flavor.

First, a solution of 1.5 g of κ-carrageenan in 110 ml of water at 85 ° C is prepared. To it are added 110 ml of preheated (80 ° C) water-soluble coffee flavor. The resulting mixture was thoroughly mixed. Then a mixture of 200 g of plant triglyceride (GRINDSTED® PS 101, mp 58 ° C) and 11 g of acetylated emulsifier (Acetem 50 00) is melted at 85 ° C in a water bath. The molten fat mixture is maintained in a homogenized state (Silverson mixer, 8000 rpm) and the aqueous mixture is slowly added. Homogenization is continued for 5 minutes after the addition of the entire aqueous mixture, and then, with continuous stirring, a solution of 0.45 g of polysorbate 80 in 15 ml of water is added. Immediately after this, the low-viscosity water-in-oil emulsion is spray-cooled in a Niro spray tower under the following conditions: inlet air temperature 10 ° C, outlet air temperature 28 ° C, spray drum rotation speed of 10,000 rpm. Get a loose powder with the aroma of coffee.

The flavoring powder is added to hot water (90 ° C), an intense aroma of coffee arises in 1 min.

Example 3. Encapsulation of nisin.

First, a solution of 15 g of k-carrageenan in 1000 ml of phthalate buffer is prepared at pH 3.5; it is prepared at 85 ° C. To this was added 300 g of a commercially available nisin extract (Nisaplin®, Danisco). The resulting mixture was thoroughly mixed. At the same time, a mixture of 1333 g of plant triglyceride (GRINDSTED® PS 101, mp 58 ° C) and 73 g of acetylated emulsifier (Acetem 50 00) is melted at 85 ° C in a water bath. The molten fat mixture is maintained in a homogenized state (Silverson mixer, 8000 rpm) and the aqueous mixture is slowly added. Homogenization is continued for 5 minutes after the addition of the entire aqueous mixture, and then a solution of 3 g of polysorbate 80 in 40 ml of water is added with continuous stirring. Immediately after this, the low-viscosity water-in-oil emulsion is spray-cooled in a Niro spray tower under the following conditions: inlet air temperature 10 ° C, outlet air temperature 28 ° C, spray drum rotation speed of 10,000 rpm. Get a loose powder. The inclusion of encapsulated nisin in a suspension medium for subsequent spraying onto food products, such as sausages, sausage casings, meat products or any other food products that require bactericides, results in a much more stable nisin-containing composition than when in suspension The media use unencapsulated or conventionally spray-cooled nisin, which dramatically increases the shelf life of nisin prior to pasteurization of the food product. For example, spray-cooled nisin is released into suspension media and therefore undergoes rapid decomposition by 57% after being in suspension media for 3 days. The encapsulated nisin used in the present example is released by only 7% in 3 days.

Example 4. Encapsulation of nisin.

First, a solution of 15 g of sodium alginate in 1000 ml of phthalate buffer is prepared at pH 3.5 and at 85 ° C. To this was added 300 g of a commercially available nisin extract (Nisaplin®, Danisco). The resulting mixture was thoroughly mixed. At the same time, a mixture of 1333 g of plant triglyceride (GRINDSTED® PS 101, mp 58 ° C) and 73 g of acetylated emulsifier (Acetem 50 00) is melted at 85 ° C in a water bath. The molten fat mixture is maintained in a homogenized state (Silverson mixer, 8000 rpm) and the aqueous mixture is slowly added. After turning on the aqueous mixture, a solution of 7 g of calcium chloride in 70 ml of water is added dropwise. Homogenization is continued for another 5 minutes and then a solution of 3 g of polysorbate 80 in 40 ml of water is added with continuous stirring. Immediately after this, the low-viscosity water-in-oil emulsion is spray-cooled in a Niro spray tower under the following conditions: inlet air temperature 10 ° C, outlet air temperature 28 ° C, spray drum rotation speed of 10,000 rpm. Get a loose powder. As noted above, the encapsulated nisin used in the present example is more stable in an aqueous medium than a sample subjected to conventional spray cooling. For example, spray-cooled nisin is released into suspension media and therefore undergoes rapid decomposition by 57% after being in suspension media for 3 days. The encapsulated nisin used in this example for 3 days is allocated only 0.1%.

Example 5. Encapsulation of sodium chloride.

First, a solution of 15 g of κ-carrageenan in 1000 ml of water at 85 ° C is prepared. 585 g of sodium chloride are added to it. The resulting mixture was thoroughly mixed. At the same time, a mixture of 1333 g of plant triglyceride (GRINDSTED® PS 101, mp 58 ° C) and 73 g of acetylated emulsifier (Acetem 50 00) is melted at 85 ° C in a water bath. The molten fat mixture is maintained in a homogenized state (Silverson mixer, 8000 rpm) and the aqueous mixture is slowly added. Homogenization is continued for 5 minutes after the addition of the entire aqueous mixture, and then a solution of 3 g of polysorbate 80 and 40 ml of water is added with continuous stirring. Immediately after this, the low-viscosity water-in-oil emulsion is spray-cooled in a Niro spray tower under the following conditions: inlet air temperature 10 ° C, outlet air temperature 28 ° C, spray drum rotation speed of 10,000 rpm. Get a loose powder.

Example 6. Encapsulation of sorbic acid.

First, a solution of 15 g of κ-carrageenan in 1000 ml of water at 85 ° C is prepared. 300 g of sorbic acid are added to it. The resulting mixture was thoroughly mixed. At the same time, a mixture of 1333 g of plant triglyceride (GRINDSTED® PS 101, mp 58 ° C) and 73 g of acetylated emulsifier (Acetem 50 00) was melted at 85 ° C in a water bath. The molten fat mixture is maintained in a homogenized state (Silverson mixer, 8000 rpm) and the aqueous mixture is slowly added. Homogenization is continued for 5 minutes after the addition of the entire aqueous mixture, and then a solution of 3 g of polysorbate 80 in 40 ml of water is added with continuous stirring. Immediately after this, the low-viscosity water-in-oil emulsion is spray-cooled in a Niro spray tower under the following conditions: inlet air temperature 10 ° C, outlet air temperature 28 ° C, spray drum rotation speed of 10,000 rpm. Get a loose powder.

Example 7. Encapsulation of calcium propionate.

First, a solution of 15 g of κ-carrageenan in 1000 ml of water at 85 ° C is prepared. 300 g of calcium propionate are added to it. The resulting mixture was thoroughly mixed. At the same time, a mixture of 1333 g of plant triglyceride (GRINDSTED® PS 101, mp 58 ° C) and 73 g of acetylated emulsifier (Acetem 50 00) is melted at 85 ° C in a water bath. The molten fat mixture is maintained in a homogenized state (Silverson mixer, 8000 rpm) and the aqueous mixture is slowly added. Homogenization is continued for 5 minutes after the addition of the entire aqueous mixture, and then a solution of 3 g of polysorbate 80 in 40 ml of water is added with continuous stirring. Immediately after this, the low-viscosity water-in-oil emulsion is spray-cooled in a Niro spray tower under the following conditions: inlet air temperature 10 ° C, outlet air temperature 28 ° C, spray drum rotation speed of 10,000 rpm.

Get a loose powder. The rate of release of calcium propionate is determined by the method using a grid. The graph is shown in figure 1.

Example 8. Encapsulation of propionic acid.

First, a solution of 40 g of low ester amidated pectin (Danisco Pectin 2580) in 750 ml of water at 85 ° C. is prepared. 250 g of propionic acid are added to it. The resulting mixture was thoroughly mixed. At the same time, a mixture of 1333 g of plant triglyceride (GRINDSTED® PS 101, mp 58 ° C) and 73 g of acetylated emulsifier (Acetem 50 00) is melted at 85 ° C in a water bath. The molten fat mixture is maintained in a homogenized state (Silverson mixer, 8000 rpm) and the aqueous mixture is slowly added. After turning on the aqueous mixture, a solution of 5 g of calcium chloride in 30 ml of water is added dropwise. Homogenization is continued for another 5 minutes and then a solution of 3 g of polysorbate 80 in 40 ml of water is added with continuous stirring. Immediately after this, the low-viscosity water-in-oil emulsion is spray-cooled in a Niro spray tower under the following conditions: inlet air temperature 10 ° C, outlet air temperature 28 ° C, spray drum rotation speed of 10,000 rpm. Get a loose powder.

Example 8

Substances and equipment

Below is described in detail all the raw materials used in the processing of samples in accordance with the present invention. A phosphoric acid-based buffer solution was prepared by dissolving 22 mmol of phosphoric acid in approximately 1.8 L of tap water, adjusting the pH to 3 by adding 1 M NaOH and adjusting the volume to exactly 2 L.

Substance Appointment Note PS101 Sheath material Triglyceride, mp Carrageenan 100 Pure κ isomer Alginate FD175 Gelatin Isoelectric point: 8.5 Pectin 1400 High ester Pectin 2580 Amidated Agar NQS 200 Xanthan KRD 246 CAP Phosphoric acid Buffer Acecem 50 Stabilization of the water-in-oil emulsion HLB 1.5 Polysorbate 80 HLB 15.4 HLB is an indicator of hydrophilic-lipophilic balance.

The mixing / emulsification step was carried out using a Silverson L4R-T mixer (Waterside-Chestam-Bucks, England) at 6000 rpm using an emulsifying head with a round hole. The final stage of spray cooling in all experiments in accordance with the present invention was carried out using an experimental Niro spray tower (Niro, Denmark) equipped with a rotating spray drum. The air temperature at the inlet and outlet was usually 10 and 30 ° C, respectively. The rotation speed of the spray drum was 8000 rpm. The feed rate to the tower was manually adjusted to set the desired outlet air temperature. NMR studies were performed using a pulsed gradient spin echo technique using a GU200 instrument (Bruker, Germany).

Methodology for the study of allocation

The isolation study was based on a standard dissolution study (USP 27, Method 711, Instrument 1), used in the pharmaceutical industry to measure the rate at which active ingredients in a pharmaceutical dosage form (e.g., tablet, capsule) dissolve. In the isolation study, a small amount of the encapsulated ingredient is placed in a wire mesh, which is then immersed in water and rotated. As the mesh rotates, the encapsulated ingredient is released and, accordingly, the amount of active ingredient in the solvent medium increases. Depending on the nature of the encapsulated ingredient, the dissolution rate can be measured by changing the pH, ion concentration (specific or complete) or by sampling and subsequent analysis by HPLC (high performance liquid chromatography). The amount of active ingredient in dissolving media is measured at certain time intervals during the study period of 60 minutes and is given in the form of a "normalized concentration" (concentration proportional to theoretical concentration in terms of the loaded amount of encapsulated product). Based on these data, it is possible to construct a selection graph representing the dependence of the increase in the normalized concentration on time (for an example, see Fig. 4).

Example 8.1. Gelled hydrocolloids.

First, 15 g of gelled hydrocolloid (s) are added to 1000 ml of water and then the solution is heated to 85 ° C. The preheated (40-60 ° C) ingredients to be encapsulated are added to the hydrocolloid solution with continuous stirring. At the same time, a mixture of 1333 g of plant triglyceride (GRINSTED® PS 101, mp 58 ° C) and 73 g of acetylated emulsifier (Acetem 50 00) is melted at 85 ° C in a water bath. The molten fat mixture is mixed with a high shear mixer (Silverson mixer, 8000 rpm) and the aqueous mixture is slowly added. Homogenization is continued for 5 minutes after the addition of the entire aqueous mixture, and then a solution of 3 g of polysorbate 80 in 40 ml of water is added, also with continuous stirring. Immediately after this, the low-viscosity water-in-oil emulsion is spray-cooled, usually in a Niro spray tower under the following conditions: inlet air temperature 0-10 ° C, outlet air temperature 25-35 ° C, spray drum rotation speed 10,000 rpm min

Example 8.2. Crosslinked hydrocolloids.

A solution of a crosslinkable hydrocolloid (hydrocolloids) in 1000 ml of water is prepared at 85 ° C. The preheated (40-60 ° C) ingredients to be encapsulated are added to it. The resulting mixture was thoroughly mixed. At the same time, a mixture of 1333 g of plant triglyceride (GRINSTED® PS 101, mp 58 ° C) and 73 g of acetylated emulsifier (Acetem 50 00) is melted at 85 ° C in a water bath. The molten fat mixture is maintained in a homogenized state (Silverson mixer, 8000 rpm) and the aqueous mixture is slowly added. After adding the aqueous mixture, a solution of 7 g of calcium chloride in 70 ml of water is added dropwise. Homogenization is continued for another 5 minutes and then a solution of 3 g of polysorbate 80 in 40 ml of water is added with continuous stirring. Immediately after this, a low-viscosity water-in-oil emulsion is spray-cooled in a Niro spray tower under the following conditions: inlet air temperature 0-10 ° C, outlet air temperature 25-35 ° C, spray drum rotational speed 10,000 rpm .

Samples

The active ingredients, coating materials, and encapsulation mixtures described above are combined to form various encapsulated food ingredients. The table below shows the compositions of the obtained and investigated samples.

Active ingredient Download, wt./wt.% Water phase Hydrocolloids Structure Pizza Flavoring 31 Water carrageenan Example 8.1 Lowlands 13 Phosphoric Acid Buffer (pH 3.5) carrageenan Example 8.1 13 alginate Example 8.2 Betaine 29th Water carrageenan Example 8.1 alginate Example 8.2 gelatin Example 8.1 pectin 1400 Example 8.1 pectin 2580 Example 8.2 agar Example 8.1 KRD / Xanthan Example 8.1 KRD / carrageenan Example 8.1 Propionate Ca ²⁺ eleven Water pH 8.5 carrageenan Example 8.1 Lemon acid 24 Water pH 3.0 pectin 2580 Example 8.2 Fumaric acid 24 Water, pH 2.8 pectin 2580 Example 8.2 KRD - locust bean gum.

The specific advantages of the encapsulated ingredients described above are discussed and compared with the prior art below.

Calcium Propionate. Spray-cooled calcium propionate is commercially available (PRO45) and is used as a preservative in baking. Encapsulation prevents the harmful effects of propionate on yeast during the first 15-20 minutes of the mixing / soaking stage. Slow release of propionate leads to an acceptable shelf life and economy of yeast compared to unencapsulated calcium propionate. The use of the encapsulated product of the present invention as an alternative to PRO45 leads to the following advantages: 1) the release of already dissolved propionate, which can reduce the browning sometimes resulting from extreme pH values in some areas, and 2) a possibly lower release rate, which will result to additional yeast savings.

Citric acid is designed to lower the pH of baked goods, such as tortillas, and acts as a preservative when other organic acids such as fumaric acid are unacceptable.

Nisin is an effective antimicrobial agent, used in many cases to increase shelf life and prevent damage by microorganisms. However, it quickly decomposes in a neutral and alkaline environment and, as a protein, is characteristically unstable at high temperature. The encapsulated nisin of the present invention may have improved thermal stability and additional controlled release ability necessary to prevent excessive decomposition during food processing. Possible applications include the use in processed or pickled meat products, processed cheese, salad dressings, bakery products, and the like.

Betaine is used in feed to replenish the nutritional value of feed for fish and shrimp. However, since it is highly hygroscopic and readily soluble in water, it is difficult to ensure a constant release for fish over a long period of time, since betaine is leached from the feed pellets before the animals eat them. Encapsulation in accordance with the present invention can prevent premature dissolution, which ensures the effective provision of betaine to fish. Spray cooling cannot lead to the formation of microcapsules that retain their contents in the aquatic environment for more than 10-15 minutes, which is not long enough for use in fish feed. These difficulties are overcome with betaine encapsulated in accordance with the present invention.

8.3 Results

8.3.1 Microscopic analysis

Figure 2 presents a sample of microparticles proposed in the present invention, examined using microscopy in transmitted light (magnification 200 ×). Particles are predominantly spherical, although there are a number of particles of irregular shape due to spray cooling. The internal biphasic core of particles (i.e., a solid water-in-oil emulsion) looks like a single mass; in this (and similar) image it is impossible to distinguish the matrix nature of the particles.

Figure 3 presents the obtained using NSEM (low vacuum scanning electron microscope) image of similar microparticles proposed in the present invention, obtained in preliminary studies. The image on the left shows the grid structure, in which 2 small spheres are visible, located in a recess in the upper left part of the image. On the right side of the image, 3 small spheres are visible. It is assumed that these small spherical particles distributed inside the larger ones correspond to gelled water droplets that contain the active ingredients. The fact that such carrier particles are not fully incorporated into the volume of the larger particle explains the rapid initial release of the ingredients within the first few minutes.

8.4 Comparison of the present invention with spray cooling

As shown in the present description, the present invention provides advantages over conventional inexpensive, but high-performance spray cooling and a more expensive and less efficient method using a fluidized bed. As shown above, the substances proposed in the present invention lead to lower production costs and greater productivity compared with spray cooling. It is also shown below that the present invention can provide lower release rates typically obtained using a fluidized bed.

Calcium Propionate. The release characteristics for the spray-cooled calcium propionate and calcium propionate encapsulated in accordance with the present invention are determined by a grid method by measuring the increase in conductivity of the solution over 60 minutes. Figure 4 compares the release graphs for two encapsulated and control (non-encapsulated) samples of calcium propionate (the "release rate" for the control sample was actually the rate of dissolution of propionate in dissolving media). The release rate for the spray-cooled calcium propionate is consistent with the results of previous experiments: approximately 75% is released in 15 minutes. As can be seen, the release rate for calcium propionate in accordance with the present invention is much slower; in 15 minutes only 20% is released. Even after 1 h, only 40% of the total amount of available calcium propionate was released and the release rate decreased, indicating that the remaining 60% would require a much longer period of time or, perhaps, even the destruction of the microcapsule by heating, loading, or other means.

Lemon acid. The release characteristics for citric acid samples obtained by spray cooling and in accordance with the present invention are compared based on the analysis of a decrease in the pH of water as the acid is slowly released from the microcapsules. The concentration of citric acid in solvents did not change with pH, regardless of the polyprotonic nature of citric acid. As can be seen from figure 5, approximately 80% obtained by spray cooling of citric acid was released in 15 minutes, which is consistent with the data for typical samples obtained by spray cooling. From figure 5 it is clearly seen that the rate of release of citric acid from the microcapsules of the present invention is significantly lower than for particles obtained by spray cooling. Within 40 minutes, only a very small amount of citric acid was isolated from the microcapsules of the present invention. To bring the pH to the final value corresponding to unencapsulated and spray-cooled samples, boiling the samples for 20 minutes was required. This result demonstrates the increased strength of the microcapsules of the present invention compared to the spray-cooled sample; in order to isolate the bulk of the encapsulated citric acid, the fat coating and hydrocolloids had to melt completely.

Lowlands. The rate of release of nisin from the spray-cooled and encapsulated samples of the present invention was measured at 30 ° C. in aqueous solvent media representing 0.02 N. HCl solution. In aliquots taken on the first, second and tenth day, the content of nisin was determined by HPLC. In the analysis, the amount of nisin contained in the dissolving media was quantitatively determined, and in fact, the amount of nisin released from the microcapsules was reduced by the amount of nisin decomposed during this period of time in acidic solvent media. The low pH of solvent media minimizes the decomposition of nisin, but does not completely prevent it. The rate of release of nisin from spray-cooled particles is much lower (days, not minutes) than for typical water-soluble ingredients, due to the polymer nature of nisin; diffusion of nisin through the fat matrix is slower due to its high molecular weight (3353 g / mol). However, it is clearly seen in FIG. 6 that the release of nisin from the microcapsules is much slower than from the spray-cooled particles: a plateau at 20% recovery is reached after 2 days for the sample of the present invention, while for the spray-cooled sample, 50% recovery It is detected after 2 days and it additionally increases to 60% after 10 days.

8.5 Effect of hydrocolloids

Betaine was chosen as a model ingredient to study whether the release rate of the ingredients encapsulated in accordance with the present invention can be finely controlled by selecting the hydrocolloid used to gel the aqueous phase. A series of samples was prepared of betaine encapsulated in accordance with the present invention with various hydrocolloids, which were either gelled by cooling or crosslinked by reaction with divalent ions. The release rate was determined by the method using the grid by sampling for 60 min and analysis using HPLC (using a detector according to the refractive index). Figure 7 presents the graphs of the allocation for samples of betaine encapsulated in accordance with the present invention, which differed only in hydrocolloids and, therefore, by the gelation mechanism for the internal aqueous phase.

You can see that the data presented in Fig.7, are divided into 3 different groups from each other. There is a significant difference between the release characteristics of the sample with the fastest and slowest release: after 15 minutes, twice as much was released from the sample with the fastest release than from the sample with the slowest release. It is noteworthy that the samples with the highest release rates were the samples in which the aqueous phase turned into a gel after cooling (for example, carrageenan, pectin 1400, mixtures of CRD and carrageenan or xanthan were hydrocolloids), while the samples in which the lowest release rates were the aqueous phase turned into a gel by crosslinking hydrocolloids (alginate or pectin 2580). Agar is an exception; although it turned into a gel after cooling, the release schedule is closer to that for samples with slow release.

The effect of hydrocolloids on the strength of the microcapsules of the present invention was also investigated using pulsed weak-field NMR. The relative stability of the gelled and crosslinked water droplets was evaluated by measuring the relaxation time T2 of the water molecules in the interior of the microcapsules of the present invention. The table below shows the time constants that best approximate the decrease in the intensity of the NMR signal after applying a sequence of pulses. The relaxation time is usually directly proportional to the mobility of the molecule in its environment: a longer relaxation time corresponds to a harder medium in which the intra- and intermolecular translational and rotational movements are limited. The table below shows that the relaxation time of water molecules in gelled carrageenan droplets is shorter than in crosslinked alginate droplets. This result shows that the aqueous phase contained in the microcapsules of the present invention obtained with alginate is harder than that obtained with carrageenan. Summarizing, we can conclude that other components of the aqueous phase based on alginate are also more limited in their movements and therefore their diffusion from microcapsules is less likely or at least proceeds at a lower rate. This result is consistent with the release schedules shown in FIG. 7, which show that content from alginate-based microcapsules is released more slowly than from carrageenan-based microcapsules.

The relaxation time of water in the microcapsules of the present invention is given below.

Hydrocolloid T ₂ (ms) T ₂ (1) T ₂ (2) Carrageenan 71.09 ± 0.07 15.8 ± 0.2 Alginate 82.5 ± 0.1 20.3 ± 0.2

8.6 Isolation due to freezing

The microcapsules of the present invention can typically contain 30-40% water. We found that the water contained in the microcapsules can crystallize and expand when frozen, thereby destroying the fat layer and promoting the release of the encapsulated ingredient. Thus, a freezing based breeding method is created. On Fig shows the obtained using microscopy in transmitted light, the image of the frozen microcapsules proposed in the present invention. The image clearly shows that the fat layer is destroyed due to the expansion of the internal aqueous phase during freezing.

8.7 Application Studies

Thermal stability of encapsulated nisin in processed cheese Way Recovery after 10 min,% At 60 ° C At 80 ° C At 100 ° C (Unencapsulated) 74 68 59 Spray cooling 75 73 72 The present invention * 90 84 75 * Sample nisin / alginate from example 8.2

Nisin in processed cheese. The nisin encapsulated in accordance with the present invention was included in the composition of the processed cheese and subjected to heat treatment for 10 minutes. The table above shows that the unencapsulated nisin was significantly decomposed even at the lowest temperature: recovery was 74% and 59% at 60 ° C and 100 ° C, respectively. Encapsulation in accordance with the present invention and spray cooling are possible ways to reduce the degradation of nisin. It can be seen that spray cooling limits decomposition by a loss of about 25% at all temperatures, while encapsulation in accordance with the present invention provides greater protection at lower temperatures and similar protection to that observed at higher temperatures when using spray cooling. These studies confirm that encapsulation in accordance with the present invention is an effective means of protecting nisin from thermal decomposition. The present invention is a particularly effective method at intermediate temperatures.

Pizza Flavors. Samples of frozen pizza were prepared 1) without the addition of microencapsulated flavoring, 2) at a low content (1 wt./wt.%, Calculated on the weight of the pizza) and 3) at a high content (2 wt. / Wt.%, Calculated on the weight of the pizza) a pizza flavor encapsulated in accordance with the present invention. Then, pizza samples were heated for 3 minutes in a microwave oven at high radiation intensity and a group of researchers studied them according to a blind scheme. All representatives of the research group noted that if a small or large flavor was added to the pizza, the pizza flavor in the room after opening the microwave door was much more intense than for the control pizza. After tasting, 3 out of 4 representatives of a group of researchers rated the intensity of flavor of pizza with the addition as more intense than for a control pizza.

The results show that the release of the ingredients encapsulated in accordance with the present invention can be controlled by heating in a microwave. A possible mechanism is that water droplets located in the inner part of the microcapsules absorb the energy of microwave radiation, expand and break off the fatty layer of the barrier, which ensures rapid penetration of water.

Discussion

We have shown that the ingredients encapsulated in accordance with the present invention are characterized by a release that is significantly and permanently less than in the case of spray cooling. Typically, spray-cooled samples released 80% of their contents in 15 minutes, and the samples of the present invention released 20-40% of their contents over the same period of time. It took only 5 minutes to isolate half of its contents from the spray-cooled samples, while for the samples of the present invention, this limit was usually reached after 60 minutes. The present invention more effectively provides a delayed release of the encapsulated ingredient than spray cooling.

We also showed that a significant portion of the encapsulated ingredient is not released at all at room temperature in the aquatic environment. This differs sharply from the characteristics of spray-cooled samples, which ultimately release all their contents in a relatively short period of time without melting the shell material. It is generally accepted that spray-cooled ingredients are released only after the fat layer is melted. It was also found that the release of the ingredient can be controlled by freezing the aqueous phase located in the interior of the microcapsules.

The experiments also showed that the release characteristics for the encapsulated sample of the present invention can be finely controlled by selecting a suitable hydrocolloid for gelation / crosslinking of the aqueous phase.

All publications noted in the above application are incorporated herein by reference. Various modifications and changes to the described methods and systems of the present invention, carried out without deviating from the scope and essence of the present invention, should be apparent to those skilled in the art. Although the present invention has been described using specific preferred embodiments, it should be understood that the present invention should not be limited to such specific embodiments. On the contrary, it is understood that various modifications of the described modes of implementation of the present invention, which are obvious to experts in the field of chemistry or related fields of technology, are included in the scope of the attached claims.

Claims (40)

1. A microcapsule comprising a hardened hydrophobic matrix shell, an encapsulated aqueous droplet or droplets that are further encapsulated in or using a hardened hydrophobic matrix shell, and an active ingredient or active ingredients dissolved in or included in an encapsulated aqueous droplet or droplets. 2. The microcapsule according to claim 1, characterized in that the encapsulated aqueous droplet is a droplet of an aqueous hydrocolloid. 3. The microcapsule according to claim 1 or 2, characterized in that the encapsulated droplet of the hydrocolloid is gelled or cross-linked droplet of the hydrocolloid. 4. The microcapsule according to claim 1 or 2, characterized in that the encapsulated aqueous droplet is encapsulated by fusion using a suitable encapsulating substance. 5. The microcapsule according to claim 4, characterized in that the encapsulating substance used in the merger is selected from the group consisting of shellac, zein, any synthetic or natural hydrophobic polymers, fats, emulsifiers, waxes, any mixture of oppositely charged hydrocolloids, such as gelatin / gum arabic, gelatin / CMC, any proteins / ionic hydrocolloids, any combination of hydrocolloids with solubility-reducing substances, such as salts, sugars, acids or bases, or sucrose acetate-isobutyrate (AIBS), damar gum, glyceryl wood ester esters or mixtures thereof. 6. The microcapsule according to claim 1 or 2, characterized in that the encapsulated aqueous droplet is encapsulated by agglomeration using a suitable encapsulating substance. 7. The microcapsule according to claim 6, characterized in that the encapsulating substance used in the agglomeration is selected from the group comprising any water-insoluble microparticles, such as silicon dioxide, titanium dioxide, granules of synthetic or natural food polymers, or any insoluble in water solids. 8. The microcapsule according to claim 1, characterized in that the encapsulated aqueous droplet includes any edible hydrocolloid that has a gelation temperature in excess of the storage temperature. 9. The microcapsule according to claim 1, characterized in that the encapsulated aqueous droplet includes any food hydrocolloid that can be crosslinked. 10. A microcapsule according to any one of claims 8 or 9, characterized in that the hydrocolloid is selected from the group comprising sodium alginate, gum arabic, gellan gum, starch, modified starch, guar gum, pectin, amidated pectin, carrageenan, gelatin, chitosan, mesquite gum, agar gum, hyaluronic acid, whey protein, soy protein, sodium caseinate, a mixture of xanthan gum with locust bean gum, cellulose derivatives such as cellulose acetate phthalate, hydroxypropyl methyl cellulose (HPMC), methyl cellulose, ethyl cellulose and carboxymethyl cellulose (CMC), methyl acrylic copolymers such as Eudragit®, plantain gum, tamarind gum, xanthan gum, locust bean gum, shellac, zein, any synthetic and natural water-soluble polymers, any food protein and mixtures thereof. 11. The microcapsule according to claim 1, characterized in that the hydrophobic shell-matrix is selected from the group comprising animal oils and fats, fully hydrogenated vegetable and animal oils, partially hydrogenated vegetable and animal oils, unsaturated, hydrogenated or fully hydrogenated fatty acids, unsaturated partially hydrogenated or fully hydrogenated monoglycerides and diglycerides of fatty acids, unsaturated partially hydrogenated or fully hydrogenated monoglycerides and diglycerides of esterified fatty acids Lot unsaturated partially hydrogenated or completely hydrogenated free fatty acids, other emulsifiers, animal waxes, vegetable waxes, mineral waxes, synthetic waxes, natural and synthetic resins, and mixtures thereof. 12. The microcapsule according to claim 1, characterized in that the active ingredient is selected from the group comprising flavorings, flavoring agents, nutrients, vitamins, preservatives, disintegrants, microorganisms, acidifiers, antioxidants, dyes, enzymes, gases, thickeners and any other pharmaceutical ingredients such as antibiotics, antimicrobials, anti-inflammatory drugs, analgesics, sedatives, hypnotics, anxiolytics, antihistamines, antiarrhythmic drugs, hypotension nye, drugs for the treatment of Parkinson's disease and hormones. 13. The microcapsule according to claim 1, characterized in that one microcapsule comprises from about 1 to 100 water droplets included in the hydrophobic matrix shell, preferably from 5 to 50 water droplets. 14. A method of producing microcapsules, comprising the steps of:
a) obtaining an aqueous phase and an active ingredient or active ingredients dissolved in or included in the aqueous phase,
b) obtaining a hydrophobic phase in molten form,
C) the inclusion or dissolution of the encapsulating substance or a mixture of encapsulating substances in the aqueous phase or in the hydrophobic phase,
g) combining the aqueous phase with the hydrophobic phase and homogenizing or mixing the combined phases to obtain a water-in-oil emulsion,
d) encapsulating the aqueous phase in the emulsion, resulting in a dispersion comprising droplets of water, and the active ingredient or active ingredients are encapsulated in droplets, and
f) processing the dispersion obtained in step e) to obtain microcapsules, in which the encapsulated droplets of water are then encapsulated in the hardened hydrophobic matrix shell or with it. 15. The method according to 14, characterized in that the aqueous phase is selected from the group comprising water and a mixture of water with any other water-miscible solvent, such as ethanol, ethylene glycol, glycerin. 16. The method according to p. 14 or 15, characterized in that the encapsulating substance is selected from the group comprising hydrocolloids, sodium alginate, gum arabic, gellan gum, starch, modified starch, guar gum, agar gum, pectin, amidated pectin, carrageenan, xanthan , gelatin, chitosan, mesquite gum, hyaluronic acid, cellulose derivatives such as cellulose acetate phthalate, hydroxypropyl methyl cellulose (HPMC), methyl cellulose, ethyl cellulose and carboxymethyl cellulose (CMC), methyl acrylic copolymers, plantain gum, tamarind gum, xanthan gum, carob gum, whey protein, soy protein, sodium caseinate, any food protein, shellac, zein, any synthetic and natural water-soluble polymers, any water-insoluble microparticles, such as silicon dioxide titanium dioxide, granules of synthetic or natural food-grade polymers and any water-insoluble solid particles capable of agglomeration. 17. The method according to 14, characterized in that the hydrophobic phase is selected from the group comprising animal oils and fats, fully hydrogenated vegetable and animal oils, partially hydrogenated vegetable and animal oils, unsaturated, hydrogenated or fully hydrogenated fatty acids, unsaturated partially hydrogenated or fully hydrogenated monoglycerides and fatty acid diglycerides, unsaturated partially hydrogenated or fully hydrogenated fatty acid monoglycerides and diglycerides, unsaturated partially hydrogenated or completely hydrogenated free fatty acids, other emulsifiers, animal waxes, vegetable waxes, mineral waxes, synthetic waxes, natural and synthetic resins, and mixtures thereof. 18. The method according to 14, characterized in that the combination of the aqueous phase with the hydrophobic phase is carried out by mixing. 19. The method according to 14, characterized in that the homogenization in stage g) is carried out by mixing with high shear or mixing on the production line. 20. The method according to 14, characterized in that the encapsulation is carried out by gelation, crosslinking, fusion or agglomeration. 21. The method according to claim 20, wherein the fusion encapsulation is carried out using an encapsulating substance and reducing the solubility of the encapsulating substance. 22. The method according to item 21, wherein the solubility of the encapsulating substance is reduced by changing the temperature, changing the pH, adding additives, or by adding hydrocolloids or any suitable fusion agent. 23. The method according to item 21 or 22, characterized in that the encapsulating substance is selected from the group comprising shellac, zein, any synthetic or natural hydrophobic polymers, as well as fats, emulsifiers, waxes or a mixture thereof. 24. The method according to claim 20, characterized in that the encapsulation by agglomeration is carried out using solid microparticles as the encapsulating substance. 25. The method according to paragraph 24, wherein the microparticles are subjected to fusion into a continuous film around the aqueous phase by heating the microparticles to a temperature above the temperature of their agglomeration or glass transition. 26. The method according to paragraph 24 or 25, wherein the encapsulating substance is selected from the group comprising any water-insoluble microparticles, such as silicon dioxide, titanium dioxide, granules of synthetic or natural food polymers and any water-insoluble solid particles . 27. The method according to claim 20, characterized in that the encapsulation of the aqueous phase is carried out by gelation and the gelation of the aqueous phase in the emulsion is carried out by lowering the temperature of the emulsion to a value lower than the gelation temperature of the encapsulating substance. 28. The method according to item 27, wherein the encapsulating substance is selected from the group comprising gel-forming hydrocolloids, such as carrageenan, gelatin, starch, modified starch, agar gum, guar gum and a mixture of xanthan gum with carob gum or a mixture of any hydrocolloid gel. 29. The method according to claim 20, characterized in that the encapsulation of the aqueous phase is carried out by crosslinking using an encapsulating substance selected from the group including any food proteins, such as soy protein, whey proteins, gelatin caseinate or starch, modified starch, chitosan, cellulose derivatives such as cellulose acetate phthalate, hydroxypropylmethylcellulose (HPMC), methylcellulose, ethylcellulose and carboxymethylcellulose (CMC), methyl acrylic copolymers, such as Eudragit ^®, any synthetic or natural astvorimye in water polymers capable of crosslinking upon exposure to heat, change in pH or chemical treatment, and a mixture thereof. 30. The method according to clause 29, wherein the crosslinking is carried out by heating, applying pressure or enzymatic crosslinking. 31. The method according to 14, characterized in that the processing in stage e) is carried out by spray cooling. 32. The method according to 14, characterized in that the processing in stage e) is carried out by cooling in a fluidized bed. 33. The method according to 14, characterized in that the active ingredient is selected from the group comprising flavorings, flavoring agents, nutrients, vitamins, preservatives, disintegrants, microorganisms, acidifiers, antioxidants, dyes, enzymes, gases, thickeners and any other pharmaceutical ingredients. 34. The method according to 14, characterized in that one microcapsule includes from about 1 to 100 water droplets included in a hydrophobic shell matrix. 35. The method according to clause 34, wherein one microcapsule includes from 5 to 50 water droplets included in a hydrophobic matrix shell. 36. The microcapsule obtained or obtained by the method according to p. 14. 37. The use of microcapsules according to claim 1 or 36 as an additive in the food industry. 38. The use of the microcapsule according to claim 1 or 36 as a flavoring, preservative or bacteriocin. 39. The use of microcapsules according to claim 1 or 36 for pharmaceutical purposes. 40. The use of microcapsules according to clause 39 in tablets-depot or systems for percutaneous administration.

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