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    • 专利摘要:
    HYBRID COACERVATE CAPSULES. The invention relates to a process for the preparation of a hybrid coacervate capsule via .da. mixing a first polymer with particles to form particle I polymer complexes; interaction of a second polymer with the polymer particle complexes, to form a mixture comprising hybrid complex coacervates containing particle inclusions; and adding a core material to the mixture, so that the hybrid complex coacervates deposit as a coating layer around the core material. The capsules form another embodiment of the invention.
    公开号:BR112014028735B1
    申请号:R112014028735-0
    申请日:2013-05-23
    公开日:2020-10-20
    发明作者:Gregory Dardelle；Pascal Beaussoubre；Philipp Erni
    申请人:Firmenich Sa；
    IPC主号:
    专利说明:

    FIELD OF THE INVENTION
    001 The invention relates to a method of preparing a delivery system, such as a flavor or fragrance delivery system, and the use of the delivery system to encapsulate a liquid, a solid, an emulsion or a dispersion that contains a flavor or fragrance. BACKGROUND OF THE INVENTION
    002 Coacervation is a liquid / liquid phase separation that occurs in polyelectrolyte mixtures, resulting in the formation of two liquid phases: one, so-called coacervate phase rich in polyelectrolyte, and a continuous diluted phase, mainly devoid of polyelectrolyte. There are two types of coacervation, namely, classic coacervation and complex coacervation, depending on whether the coacervate phase consists of a single polymer or an ionic complex of two oppositely charged polymers. In the classic complex coacervation process, used for the encapsulation of active ingredients, phase separation is induced so that the coacervate phase readily lines the drops or particles of the active ingredient. For encapsulation purposes, at least one of the polymers used must also be able to form a gel upon cooling. The process is conducted above the gelation temperature, and the temperature is reduced after coating the active ingredient (the core material) with a complex coacervate phase, leading to temperature-induced gelation. Optionally, this procedure is followed by a hardening step, during which the coacervate coating of the capsule is still cross-linked, to provide a mechanically stable barrier coating. The classic coacervation process is described in a variety of publications, including WO 96/32017 (Tastemaker), FR 1,165,805 (The National Cash Register Company), MX 9,704,934 (Tastemaker Corporation), US 6,325,951 ( Givaudan), EP 0455598 (Warner-Lambert), EP 2150334 (Firmenich) and WO 2004/022221 (Firmenich).
    003 Capsules with coating or matrices not exclusively made of polymers have also been disclosed. US 4,394,287 describes, for example, the use of water-insoluble additives, such as nacreous materials, metallized flakes, optical brighteners and UV absorbers embedded in a polymer and coated on the surface of the microcapsule. This forms types of double layer capsules with limited stability and also presents a risk of delamination under certain stress conditions. US 4,115,315 describes the use of nacreous particles embedded in the capsule wall. The aim is to provide only a visual effect and the document is silent on any other functionality of the capsule. In terms of process, the particles are firstly added to the oil phase (internal phase material). The resulting dispersion is then added to an aqueous encapsulation medium, during which the particles are washed in the aqueous coacervate before grinding and, finally, hardening. However, with this process, the migration of particles in the gel phase is limited. Therefore, the particles are preferably concentrated at the oil / gel interface and not evenly distributed within the capsule wall. On the other hand, publication WO 2004/022220 A1 (Southwest Research Institute) refers generally to the preparation of core / coating microcapsules which comprises a membrane that is made of a material of a single polymer and a structuring agent dispersed within it to protect core materials with at least one oxygen sensitive ingredient. The disclosure mentions, in very generic terms, different possible methods of microencapsulation, in particular, atomization, coacervation and coextrusion. Although complex coacervation is cited as an option, only classical coacervation is obviously considered, unless the structuring agent is added to the surface of the capsules. According to this teaching, the structuring agent can be added either after the formation of the emulsion and / or by addition to the oil phase. Examples are presented to demonstrate the oxygen barrier properties and to describe the use of clay particles (kaolin), combined with a single polymer (gelatin) (classic coacervation), to obtain a membrane with improved barrier properties.
    004 WO 2005/072228 A2 (E Ink) refers to the preparation of capsules, especially capsules intended for use in the formation of electrophoretic media, through a coacervation process to better control the size distribution of the core-coating capsules , or by emulsifying a water-immiscible phase in a preformed protein coacervate (which, in essence, is a classic coacervation process) or using a limited coalescence process, with colloidal alumina as the surface active particulate material, or that is, forming a stabilized solid emulsion as an essential step in the process.
    005 WO 2009/147119 (Symrise) refers to a capsule with an organic / inorganic hybrid wall. This publication describes synthetic polymer core / shell capsules, where the term "hybrid" refers to the presence of Si atoms in the synthesized silicon polymers. It does not reveal capsules containing inorganic (or other) particles included in the wall, and does not refer to coacervation methods.
    006 WO 2010/125094 refers to the encapsulation of liquid or pasty active materials, by extrusion through a nozzle, where the encapsulation material is described as a crosslinkable inorganic-organic hybrid material, at least partially condensed, organically polymerizable, such as organopolysiloxanes. The term "hybrid" refers to the inorganic nature of Si atoms present in organosilicon polymers used for a matrix encapsulation process.
    007 WO 2011/124706 (BASF) relates to microcapsules having an encapsulated core material within a microcapsular coating useful for encapsulating flavor, perfume or fragrance, wherein the coating comprises at least one inorganic / hybrid material. It describes a process for preparing microcapsules in which a sun / gel precursor is mixed with a fragrance, perfume or flavor, to form the liquid of the oily core, followed by emulsification of that oil to form an oil-in-water emulsion and, subsequently go through a sol / gel process, resulting in capsules with a metal oxide or an inorganic / organic hybrid coating. This document discloses coating materials where polymeric or organic materials have been added to the coating or capsule.
    Despite these disclosures, there is a need for improved methods of producing core-coating capsules having coatings with desired mechanical properties, improved barrier properties of encapsulated materials and other desired functional properties. Such methods are now provided by the present invention. SUMMARY OF THE INVENTION
    One embodiment of the present invention relates to a process for preparing a hybrid coacervate capsule. This process comprises mixing a solution of a first polymer with a dispersion of at least one type of solid particles, at a temperature that is above the gelation temperature of the first polymer, where the first polymer adsorbes on at least one type solid particles, to produce a dispersion of particle / polymer complexes; adding a solution of a second polymer to the dispersion, where the second polymer interacts with the particle / polymer complexes, to form hybrid complex coacervates containing particle inclusions; the addition of a core material to the hybrid complex coacervates, in which the hybrid complex coacervates deposit as a coating layer around the active core material / solution interface, to form core / coating capsules, each containing the core material. core encapsulated by a hybrid coacervate coating; and reducing the temperature of the core / coating capsules to a temperature that is less than the gelation temperature of the first polymer. Optionally, but preferably, the process includes the crosslinking of hybrid capsule coacervate coatings.
    0010 The solution of the first polymer is usually mixed with the dispersion of at least one type of solid particles, under conditions sufficient for the first polymer to readily adsorb on the at least one type of solid particles, the pH value and ionic strength of the solution being of the first polymer optimized for the formation of particle / polymer complexes. In addition, the hybrid coacervate has an adequate viscosity which allows the hybrid coacervate to deposit on the core material to form the capsule lining. Generally, the viscosity of the hybrid coacervate is between 100 mPas and 2,500,000 mPas, at a temperature between 30 ° C and 70 ° C, and with shear rates between 0.01 / s and 100 / s, and the hybrid coacervate contains at least one, and more preferably two or more types of solid particles.
    Another embodiment relates to a core / coating capsule produced according to the processes described herein. The capsule shell contains at least one, and, more preferably, two or more different types of solid particles that are generally selected from the group consisting of silicon oxides and other metal oxides, silicates, silver, magnesium nanoparticles and silicates aluminum (clays), phyllosilicates (mica), diatomite, perlite, vermiculite, fat crystals, fatty acids or fatty alcohols, and mixtures thereof. In a preferred form, the capsule is transparent and has the appearance of glass spheres, in which the core is lighter than water, but the capsule settles under gravity or in centrifugal fields. In addition, the core may include a solid active ingredient and / or a liquid active ingredient, the latter usually being an oil.
    The capsule thus comprises a core and a coating, wherein the coating is a hybrid coacervate material composed of two coacervate polymers and at least one type of solid particles; and the core comprises a solid active ingredient and / or a liquid active ingredient in an oil. BRIEF DESCRIPTION OF THE DRAWINGS
    0013 Figure 1 shows a schematic drawing of the hybrid coacervation process of the invention.
    0014 Figure 2A shows a comparison between opaque hybrid coacervate capsules with a gelatin / gum arabic / kaolin coating (upper part of the figure) and classic transparent gelatin / arabic coacervate capsules (bottom of the figure).
    0015 Figure 2B shows drops of non-encapsulated (free) oil next to gelled hybrid coacervate granules, resulting from the use of a hybrid coacervate material made from (gelatin / arabic / kaolin) in the mass ratio (1 , 5/1/4), which does not deposit properly on the core material and does not form a coating.
    0016 Figure 3 shows microscope images of classic coacervate capsules (Conventional) compared to hybrid coacervate capsules with two different gelatin / arabic / kaolin coating compositions (Hybrid 1 and Hybrid 2). The figure also shows the effect of the Hybrid 1 and Hybrid 2 coating composition on the relative density of all capsules in a slurry: Hybrid 1 coated capsules rise to the top of the sample bottle, while Hybrid 2 coated capsules settle. at the bottom of the bottle.
    0017 Figure 4 shows the relative headspace concentration of an active ingredient (limonene) in relation to the flow rate of dynamic headspace measurements on classic coacervate capsules that do not contain particles (without particles) and hybrid coacervate capsules that contain particles ( with particles).
    0018 Figures 5A and 5B show an iridescent visual effect of hybrid coacervate capsules with coating containing gelatin / gum arabic / mica, little (A) and very (B) enlarged. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
    The invention provides a new method of producing core / coating capsules with coatings with a significant amount of particle inclusions. Such coating compositions provide unexpected benefits for the core / coating capsules of the invention, such as desired mechanical properties; adjusted capsule coating density; improved processability and easy drying of the capsule; better barrier properties of the encapsulated material; reduced water content in the coating and desired functional properties, including, but not limited to optical properties such as color, opacity and iridescence; protection of active ingredients (for example, radiation absorbers to protect from UV radiation); release (for example, secondary encapsulation of an active or “coactive” solid ingredient in the coating); release and protection of the secondary active ingredient in the coating; masking (for example, the coating contains smelly capture particles and the core contains a fragrance); and nutritional / health benefit (eg, iron).
    0020 For the purposes of the present invention, the term "hybrid coacervate capsule" means a core / coating capsule where the capsule coating layer is produced by means of complex three-component coacervation, which involves two polymers and at least one type of solid particles. In contrast, the term “classic coacervate capsule” refers to a core / coating capsule made by means of classic complex coacervation, a well-known and well-established encapsulation process that has been widely used for paints, flavorings, fragrances and others active ingredients.
    0021 Capsule core material
    0022 The core material of the hybrid coacervate capsule can be a liquid or solid hydrophobic material. Such hydrophobic materials are generally immiscible with water and form a separate phase when mixed with water.
    Preferably, the hydrophobic material is a hydrophobic liquid at room temperature, which is totally or partially immiscible with water, so that it can be dispersed in the form of discrete drops of emulsion within an aqueous phase, during the production of the capsules. This requirement usually implies that the interfacial tension of the liquid active ingredient against water is at least 0.0001 N / m, and preferably at least 0.001 N / m. In addition, the hydrophobic material preferably contains at least one component for which the value of the base ten logarithm of the partition coefficient between octanol and water (logP) is greater than 4. However, the hydrophobic material may also contain additional components with logP <4.
    0024 For the purpose of the present invention, the term "hydrophobic material" also includes materials that remain solid at the temperatures of the process described herein. Preferably, such solid hydrophobic materials also form a separate phase with water, when heated above its melting point.
    0025 Preferred hydrophobic materials for the capsule core include flavorings, fragrances, pigments, dyes, sweeteners, cooling agents or other ingredients with organoleptic activity, nutritional ingredients, food supplements, therapeutic agents, drugs or other bioactive agents.
    Flavors and fragrances are particularly preferred for the purpose of the present invention. For the purpose of the present invention, the terms "flavoring" and "fragrances" include a variety of flavoring materials and fragrances of natural or synthetic origin, including individual compounds and mixtures thereof.
    0027 Specific examples of these ingredients can be found in the current literature, for example, in the Fenaroli Flavor Ingredients Manual, 1975, CRC Press; Synthetic Food Adjuncts, 1947, by M.B. Jacobs, edited by Van Nostrand; or in Perfume and Flavor Chemicals, 1969, by S. Arctander, Montclair, NJ (USA). These substances are well known to the person skilled in the art of perfuming, flavoring and / or aromatizing consumer products, that is, to impart or modify the odor, flavor or taste of a traditionally perfumed consumer product, respectively flavored. More recent versions of such textbooks also describe several examples of suitable perfuming and / or flavoring ingredients and their mixtures.
    0028 The state of the art and, in particular, the patent literature in the field of flavor and fragrance is also rich in such citations.
    0029 Natural extracts can also be encapsulated in the system of the invention, including, for example, extracts of citrus fruits such as lemon, orange, lemon, grapefruit or tangerine oils, or coffee, tea, mint, cocoa, vanilla oils or essential oils of herbs or spices, among others.
    0030 Preferably, ingredients with organoleptic activity also include capsaicin, cooling agents and nutritional ingredients.
    According to a particular embodiment, the core further includes solid particles dispersed therein, such as those described below.
    0032 Capsule shell / membrane
    In preferred embodiments of the invention, the coating / membrane of the hybrid coacervate capsule of the invention comprises two coacervate polymers, a first polymer ("polymer 1") and a second polymer ("polymer 2") and at least one type of solid particles. Solid particles, of at least one type, provide the desired benefits, such as reducing the amount of water in the membrane and other functional properties, to the hybrid coacervate capsule. The first polymer, polymer 1, is selected based on its ability to interact with solid particles, to form a first polymer / particle complex that is positively or negatively charged. The second polymer, polymer 2, then interacts with the first polymer / particle complex, to induce phase separation. The hybrid coacervate set is specially designed to be able to deposit on the surface of the active ingredient, to encapsulate the latter. Such deposition results in a core / coating capsule comprising a coating that contains solid inclusions retained in a polymeric gel matrix.
    The polymers can be, for example, proteins, polysaccharides and polyacids which are generally known to be suitable for complex coacervation methods.
    In some preferred embodiments, the first polymer, polymer 1, is a protein or polypeptide capable of adsorbing on the surface of the particles to form a new complex that is positively or negatively charged. The proteins suitable for coacervation processes are gelatins and albumins or globulins of plant, animal or microbial sources. The typical molecular weights of proteins useful for the hybrid coacervation process are in the range of 40 KD to 500 KD, preferably 15 KD to 250 KD. In one embodiment, the protein is present as an aggregator or oligomer, so that the molecular weight is much greater. Suitable proteins include gelatins, whey proteins (such as lactoglobulin), pea proteins, potato proteins or egg albumins (for example, ovalbumin), caseins and caseinates.
    In a preferred embodiment, the first polymer, polymer 1, is a protein, the solution of which forms a gel upon cooling. For the purpose of the present invention, the gelation temperature of the first polymer, polymer 1, is considered to be the relevant gelation temperature for the hybrid coacervate system.
    In a preferred embodiment, the first polymer, polymer 1, is a gelatin. Suitable gelatines can be derived from a variety of sources, such as sources of pork, beef, poultry or fish. The gelation temperatures of such gelatines are usually in the range of 29 ° C to 36 ° C. For a specific gelatin, the gelation temperature must be measured by oscillatory rheometry, using defined laboratory methods. For the gelatines used here, the gelation temperature is determined in gelatine solutions using a Physíca MCR300 rheometer (Anton Paar GmbH, Germany), equipped with parallel measuring plate geometry (disc diameter 50 mm, clearance 0.75 mm), programmed to perform a temperature sweep test from a temperature of 60 ° C to a temperature of 15 ° C, with a temperature ramp of -1 ° C / min, at a controlled strain range of 2 % and an oscillation frequency of 1 rad / s.
    In a preferred embodiment of the invention, the first polymer, polymer 1, is positively charged to pH <8, resulting in low viscosity solutions in water at a temperature greater than the melting point of the polymeric gel considered, and more preferably, at T> 30 ° C, and highly viscous solutions in water at room temperature. In a preferred embodiment, the first polymer, polymer 1, is gelatin.
    In some preferred embodiments, the second polymer, polymer 2, is a non-protein polymer charged opposite the protein of the first polymer, polymer 1, in the range of pH values that are known to be of interest for coacervation. These non-protein polymers include gum arabic (also known as acacia gum or acacia gum) and similar plant gums, tragacanth gum, CARBOPOL® poly (acrylic acid), low methoxyl group pectin, xanthan gum, carboxymethyl de sodium from guar gum, guar gum, pectin with a high content of methoxy groups, carboxymethylcellulose (CMC), alginates, carrageenans (including kappa-carrageenan, iota-carrageenan, lambda-carrageenan, and mixtures thereof), dextran sulfate, polyphosphates (for example, sodium hexametaphosphates) or bacterial exopolysaccharides. Details on the characteristics of suitable polymers can be found in the scientific literature on coacervation and in polyelectrolyte complexes (for example, in de Kruif CG, Weinbreck F., de Vries R., Current Opinion in Colloid & Interface Science 9: 340- 349, 2004).
    0040 Preferably, the second polymer, polymer 2, is chosen from the group of weakly anionic polyelectrolytes including gum arabic and similar plant gums, carboxymethylcellulose, low methoxy pectin, carbopol, guar gum sodium carboxymethyl and alginates.
    More preferably, the second polymer, polymer 2, is negatively charged when the pH is greater than 2. In a preferred embodiment, the second polymer, polymer 2, is gum arabic.
    0042 The solid particles included in the hybrid coacervate coating represent a new feature of the invention. These particles provide benefits including, but not limited to an improvement in the barrier properties of the coating, a change in the density of the capsule, a reduction in the amount of water in the coating and other benefits relevant to a specific functionality of the capsule, such as the nutritional value of the capsules. solid particles, desirable visual properties, radiation protection and responsiveness to a magnetic field to move or separate the capsules.
    0043 Solid particles include, but are not limited to, groups of inorganic particles, such as clays; organic particles, such as latex, starches, microcrystalline cellulose, cyclodextrin, and mixtures thereof; composite of nano or microparticles, such as porous particles containing a secondary active ingredient; particles that carry immobilized enzymes; nano / macro fiber; and nano / macro tube. In particular, the solid particles can be silicon oxides, such as silica (for example, colloidal silica, such as that sold under the trademark of KLEBOSOL® by AZ Electronic Materials, or sublimated silica, available, for example, under the brand name AEROSIL® trademark) by Evonik) or silicates (eg synthetic silicate, such as the one sold under the LAPONITE® trademark by Rockwood Additives) ', other metal oxides, such as iron oxide, aluminum oxide, aluminum oxide titanium; metallic salts and their derivatives; hydroxides, salts of inorganic or organic acids, and mixtures thereof (for example, TiO2, FeO, Fe (OH) 2, FeCOa, MgO, Mg (OH) 2, MgCOa, Mg3 (PO4) 2, CaCOa, CaSO4, Cas ( PO4) to (OH), Caa (C6H5O ) 2); silver nanoparticles; magnesium and aluminum silicates (clay); phyllosilicates (mica); diatomite; perlite; vermiculite; polymer latex; dietary fibers, such as microcrystalline cellulose; lignin and chitin; cells (for example, yeast cells) or fragments thereof; organic acids; enteric polymers (eg EUDRAGIT® FS 30 D and EUDRAGIT® L 100-55 from Evonik) ', fat crystals, fatty acids or fatty alcohols, and mixtures thereof.
    0044 In a preferred embodiment, types of solid particles include oxides of silicon and other metal oxides, silicates, silver nanoparticles, magnesium and aluminum silicates (clay), phyllosilicates (mica), diatomite, perlite, vermiculite, fat crystals, fatty acids or fatty alcohols, and mixtures thereof.
    In a preferred embodiment of the invention, solid particles are negatively charged when the pH is greater than 2.
    In one embodiment of the invention, the first polymer, polymer 1, adsorb on the surface of the solid particles to form a new positively charged polymer / particle complex (a) at pH> 2. The particle coverage by the first polymer, polymer 1, is preferably at least 0.1 molecules of polymer 1 per nm2 of particle surface.
    In one embodiment of the invention, the particles are less than 10 micrometers in at least one dimension.
    In any embodiment of the invention, it is preferable that the dry matter composition of the hybrid coacervate coating is such that the ratio of the total mass of solid particles to the total mass of polymers 1 and 2 is between 0.01 and 1, 85.
    0049 Crosslinking agents
    0050 After the formation of the hybrid coacervate coating, the coating is normally hardened using a crosslinking agent. Suitable cross-linking agents include, but are not limited to, formaldehyde, acetaldehyde, glutaraldehyde, glyoxal, chromium alum and transglutaminase. The transglutaminase enzyme, which is readily available commercially (for example, from Ajinomoto Corp., Japan) is preferably used from 10 to 100 units of activity per gram of the first polymer, for example, gelatin, and, more preferably, from 30 to 60 units of activity per gram of the first polymer.
    0051 Preparation method
    The invention provides a process for the preparation of hybrid coacervate capsules of the invention, the process of which comprises the steps of:
    0053 (1) mixing a solution of a first polymer (solution A) with a dispersion of at least one type of solid particles (dispersion C), at a temperature that is above the gelation temperature of the first polymer, thereby adsorbing the first polymer on the at least one type of solid particles, to form a dispersion of particle / polymer complexes;
    0054 (2) adding a solution of a second polymer (solution B) to the dispersion of particle / polymer complexes formed in step (1) to interact with the particle / polymer complexes, thereby forming complex hybrid coacervates containing inclusions of particles;
    0055 (3) addition of a core material (D) to the complex hybrid coacervates formed in step (2), which are deposited as a coating layer around the active core material / solution interface, to form core / coating capsules with a hybrid coacervate coating,
    0056 (4) temperature reduction of the core / coating capsules below the gelation temperature of the first polymer, and, optionally,
    0057 (5) hardening of the hybrid coacervate coating of the capsules by crosslinking the protein fraction of the hybrid coacervate coating.
    In a preferred embodiment of the invention, step (1) is carried out under conditions sufficient for the first polymer to readily adsorb onto the solid particles. Preferably, step (1) is carried out by adjusting the pH value and / or the ionic strength of solution A, to optimize the formation of particle / polymer complexes.
    The sequence of steps (1) to (5) is an essential feature of the present invention. Following the previously described processes of including particles in the coating of a capsule, in the case of capsule membranes formed by complex coacervation of two polymers and particles, it would not allow the same result. In particular, WO 2004/022220 A1 (Southwest Research Institute) teaches that particles can simply be added at any time during the process. This approach, which teaches to ignore steps (1) and (2) of the method of the present invention, results in failure of the encapsulation, since a complex hybrid coacervate containing particles can only be formed if an adequate dispersion of the polymer 1 / particle complexes.
    0060 Adjustment of the capsule lining density
    0061 The density of hybrid coacervate capsules is easily controlled by modifying the amount of particle inclusions in the coating / membrane. Unlike conventional capsules that are the same size and contain the same core material as the hybrid coacervate capsules of the invention, but made by classic coacervation that always floats, the hybrid coacervate capsules of the invention can be modified either to float or to sedimentary, including different amounts of particles (see Fig. 3).
    0062 Improved barrier properties of encapsulated material
    0063 The inclusion of solid particles in the coating / membrane of the hybrid capsules makes it possible to improve the barrier properties and reduce the permeation of the active ingredient through the coating. The preparation of capsules with a hybrid coacervate coating with solid particles according to the invention allows the formation of a more densely packed inorganic polymer / particle coating. This is especially pronounced after removing the water from the membrane, after drying the capsules.
    0064 Hybrid coacervate capsules with desired functional properties
    0065 By choosing solid particles with specific functional properties, hybrid capsules with desired functional properties can be prepared. For example, this can be achieved by choosing particles with desired optical properties (such as color; opacity; iridescence), desired protective properties (such as using radiation absorbers to protect the core of the active ingredient from ultraviolet radiation) and benefits nutritional / health (with particles such as iron oxide or minerals).
    0066 Hybrid coacervate capsules produced using the method of the invention have multiple uses. For example, they can be used in food and beverages where capsules made by coacervation are commonly used, including, but not limited to meat products, bakery products, cereal products, confectionery products, including chewing gums, preserves and pates, dairy products, such as yogurts and other fermented dairy products, dairy drinks and cheeses, frozen salty foods such as pizzas, meat preparations and sandwiches, frozen sweet products such as ice cream, sorbets and frozen yogurts, and oral care products , such as toothpastes, gels and mouthwashes.
    0067 The hybrid coacervate capsules of the invention can also be used in perfumery applications, where capsules made by means of coacervation can be used, including, but not limited to body wash products, such as shower gels and soaps, body hygiene, such as body creams and lotions, and air care products or fine perfumery. The hybrid coacervate capsules of the invention can also be used in products such as sunscreen lotions, deodorants and antiperspirants. EXAMPLES
    The following examples are provided as illustrations of preferred embodiments of the invention and are not intended to limit the scope of the invention. Example 1
    0069 Preparation of hybrid coacervate capsules with coating composed of gelatin, gum arabic and kaolin particles
    0070 Watery solutions of 10% by weight of pig gelatin (A), 10% by weight of gum arabic (B), an aqueous dispersion of 10% by weight of kaolin particles (C) and limonene oil (D) are prepared separately and kept at 50 ° C in a water bath. In a beaker, at 50 ° C, 15 g of solution (A) are added to 35 g of demineralized water under mechanical shear. The pH of the solution is adjusted to 8.5 using 1M NaOH, before adding 40 g of dispersion (C), and reducing the pH to 4.5 with HCl1M. Then, 10 g of solution (B) is added to the mixture, followed by the addition of 10 g of the oil (D). Mechanical shear is maintained while the solution is left to cool to room temperature. The result is a suspension of core-coating capsules that sediment at the bottom of the beaker, that is, with a density different from that of the capsules prepared without particles, and which exhibits an opaque appearance with a white color. Thermogravimetric analysis of the residual solvent showed that there is no polymer, and no particles remained in the solvent after this process.
    0071 The density of the capsule in its entirety can be easily controlled by modifying the amount of particle inclusions in the membrane. The comparison of conventional capsules with coatings made by means of classical coacervation with hybrid coacervate capsules (both samples with the same sizes and containing the same core material) reveals that hybrid coacervate capsules can be manipulated or to float or to sedimentary, depending on the composition of the hybrid coacervate coating.
    0072 The compositions of conventional coating capsules and two different types of hybrid capsules are shown in the table below. As shown in Fig. 3, the density of the capsules that have hybrid coacervate coatings can be modified by changing the amount of inorganic kaolin particles included in the coating.
    Example 2
    0073 Preparation of hybrid coacervate capsules with coatings composed of gelatin, gum arabic and silica particles
    0074 Water solutions of 10% by weight of pig gelatin (A), 10% by weight of gum arabic (B), watery dispersions of 10% by weight of silica particles (KLEBOSOL®30V25, obtained from AZ Electronic Materials) (C) and limonene oil (D) are prepared separately and maintained at 50 ° C in a water bath. In a beaker at 50 ° C, 15 g of solution (A) are added to 70 g of hot demineralized water under mechanical shear. The pH is adjusted to 8.5 using 1 M NaOH before adding 5 g of solution (C), and reducing the pH to 4.5 with 1M HCI. Then, 10 g of solution (B) is added to the mixture, followed by the addition of 10 g of (D). Mechanical shear is maintained while the solution is left to cool to room temperature. The result is a suspension of core-coated capsules that is easier to dry compared to conventional capsules that do not contain particles, and that exhibit a different release of the encapsulated material when dried compared to conventional capsules:
    0075 Coating of conventional coacervate capsules: gelatin / gum arabic / silica mass ratio = 1.5 / 1/0.
    0076 Coating of hybrid coacervate capsules: gelatin / gum arabic / silica mass ratio = 1.5 / 1 / 0.5.
    0077 Release measurement after drying
    0078 In a small crystallization disk, a few drops of the capsule slurry were diluted with 1 ml of deionized water. From this suspension, individual medium-sized capsules were selected and transferred to a 13 mm diameter fiberglass disc (Whatman GF / B). Fifteen capsules were deposited on the disc. Water was required for the transfer, but care was taken to include only the smallest amount of water possible in the disc in order to maintain its permeability. To remove excess water, the disc was placed on several layers of filter paper. The disk containing the dried capsules was then introduced into the flow cell and the headspace analysis (Fig. 4) was carried out as follows: The surface of the liquid was subjected to four different nitrogen flow rates (13.3, 23, 1.45.8 and 90.3 mL / min), at a controlled temperature and saturated with water, with each flow rate applied for 10 minutes. A 1 ml aliquot of the gas in the cell was sampled at 1 minute intervals by an automatic CTC Analytics PAL sampler, and injected into a CG / EM system (Agilent 6890 / Agilent 5973) for analysis. The headspace measurement was performed at 32 ° C, and the peak area was normalized by the peak area obtained for pure limonene under static conditions, at the same temperature (Po). Following this protocol, each point plotted for P / Po is an average of about 10 different values. Measurements were performed in triplicate.
    The key result is that the diffusion of limonene across the hybrid capsule membrane is reduced by 50% to 56%, compared to conventional coacervate capsules. Although the mechanism underlying this phenomenon is unknown, it is possible that a more densely packed polymer / inorganic coating will be formed after water is removed during drying. Ultimately, this significant result suggests a less permeable structure for hybrid capsules, after removal of the aqueous phase in the membrane. Example 3
    0080 Example 3a: Alternative preparation of hybrid coacervate capsules with coating composed of gelatin, gum arabic and silica particles
    This comparative example demonstrates an unsuccessful attempt to obtain hybrid coacervate capsules when the process described in the present invention has not been followed. In particular, the inability to obtain complexes of polymer 1 and solid particles led to the subsequent failure of the formation of a hybrid coacervate coating, the result of which is classic coacervate capsules with freely suspended solid particles, which are not integrated into the capsule coating.
    As in Example 2, in a beaker at 50 ° C, 15 g of solution (A) and 10 g of solution (B) are mixed and added to 35 g of hot demineralized water, under mechanical shear. The pH is adjusted to 4.5 with HC11 M, before adding 40 g of dispersion (C) to the solution, and the pH is readjusted to 4.5, if necessary. Then, 10 g of solution (D) are added to the mixture, under mechanical shear, until the mixture reaches the desired droplet size. The solution is kept under stirring and cooled to room temperature. The result is a suspension of core-coating capsules exhibiting a translucent coating without particle inclusions. The particles are located and dispersed in the continuous aqueous medium. Unlike Examples 1 and 2, there is no formation of polymer 1 complexes and particles, and subsequently, particles were not included in the coacervate coating of the capsules.
    0083 Example 3b: Alternative preparation of hybrid coacervate capsules with coating composed of gelatin, gum arabic and kaolin particles
    0084 This comparative example shows that a hybrid coacervate phase was formed, but the essential step of depositing that hybrid coacervate on the core material was not successful, so that it was not possible to encapsulate the liquid from the oily core.
    0085 Two different samples of the hybrid coacervate phase were prepared at a mass ratio of 1.5 / 1/4 of gelatin / gum arabic / kaolin, and the pH was adjusted to 4 and 4.5, respectively. In both cases, complete phase separation was achieved, including polymers and solid particles, resulting in dense, irregularly shaped nodules containing both the polymers and the kaolin clay particles. After mixing the limonene oil, none of these hybrid particles were deposited on the oil droplets, as in the successful Examples 1 and 2 described above, and it was found that all fragments of hybrid coacervate gel remained suspended and pelleted on the bottom. of the mixing beaker, as shown in Fig. 2B.
    0086 Example 3c: Encapsulation process with adjusting the viscosity of the hybrid coacervate lining material, to allow its deposition on the core material
    In this example, an encapsulation process is carried out according to the procedure indicated in Examples 1, 2 and 3b. In addition, the viscosity of the hybrid coacervate coating is controlled by carrying out rheological tests in parallel to the encapsulation tests. The hybrid coacervates were made of gelatin (polymer 1), gum arabic (polymer 2) and kaolin particles, and different mass ratios (polymer 1: polymer 2: particles) were tested.
    0088 The rheometer is a Physica MCR 300 (Anton Paar, Ostfildern, Germany) and a parallel plate geometry (50 mm in diameter, measuring range of 1 mm was used; the measuring device in contact with the sample had corrugated surfaces for avoid the problem of sliding the wall during measurement). Dynamic viscosity is measured by carrying out a controlled shear speed ramp with increasing and decreasing shear speed, while controlling the temperature with the built-in temperature controller of the Peltier rheometer. Different phases of hybrid coacervate were prepared as described in Examples 1,2 and 3b, but, in parallel, a volume of 20 ml of each phase of hybrid coacervate was removed and used to measure viscosities (in SI units of mPa * s, that is, milliPascal * second). Viscosities are compared with shear rates of 100 / s, 1 / s and 0.01 / s, which are characteristic shear rates of the mixing and deposition steps of the encapsulation process, and measurements were made at temperatures ranging from 30 ° C and 55 ° C.
    The results show that, for the mass ratio (1.5 / 1/3) and pH 4.5, as in Example 1, the viscosity measured at a shear rate of 1 / s was 23,450 mPa * s, at 30 ° C, 940 mPa * s at 37.5 ° C and 390 mPa * s at 55 ° C. The lowest overall viscosity value was measured at a shear rate of 100 / s, at 55 ° C, and its value was 255 mPa * s. The highest apparent viscosity was measured at the slowest shear rate of 0.01 / s, at 30 ° C, and was 550,000 mPa * s. It was found that the hybrid coacervate material with these properties is easily deposited on the core material during the process.
    0090 On the other hand, with reason (1.5 / 1/4) and pH 4, the viscosity values were increased. In particular, at a shear rate of 1 / s, the viscosity was 49,320 mPa * s, at 30 ° C, 1,325 mPa * s at 37.5 ° C, and 405 mPa * s at 55 ° C. The lowest viscosity measured on the sample heated to 55 ° C and with a fast shear speed of 100 / s was 270 mPa * s, which is comparable, in magnitude, to the mass ratio described above. However, at the slow shear speed, the highest apparent viscosity was strongly increased with a very high viscosity value of 2,400,000 mPa * s, at 30 ° C. In this case, it was found that the hybrid coacervate material was too viscous to deposit on the core material during the process (Fig. 2B). Thus, instead of core / coating capsules, only gelled granules of hybrid coacervate and free drops of the core material were found in the resulting mixture.
    0091 These experiments, therefore, allow us to demarcate the viscosity limit values within which a hybrid coacervate material composed of two polymers and particles can be successfully formed, in such a way that it includes a high mass fraction of particles and yet be able to deposit easily on the core material. Example 4
    0092 Preparation of hybrid coacervate capsules with functional particles to provide desired optical properties or attractive visual appearance
    0093 This example describes the preparation of hybrid coacervate capsules coated with gelatin, gum arabic and particles, providing additional functionality to the capsule, including attractive optical appearance, such as opalescence, color and iridescence (shown in Figure 5).
    0094 Aqueous solutions 10% by weight of pig gelatin (A), 10% by weight of gum arabic (B), an aqueous dispersion 10% by weight of mica particles (C) and limonene oil (D) are prepared separately and kept at 50 ° C in a water bath. In a beaker at 50 ° C, 15 g of solution (A) are added to 70 g of hot demineralized water under mechanical shear. The pH is adjusted to 8.5 using 1 M NaOH before adding 10 g of solution (C), and reducing the pH to 4.5 with 1M HCI. Then, 10 g of solution (B) are added to the mixture, followed by the addition of 10 g of oil (D). Mechanical shear is maintained while the solution is left to cool to room temperature.
    The example provided here can be easily modified, for example, to include particles that are radiation absorbent (for example, for UV protection). Example 5
    0096 Preparation of hybrid coacervate capsules with iron oxide inclusions in the coating
    0097 This example demonstrates the formation of hybrid coacervate capsules containing Fβ2θ3 particles in the coating.
    0098 Aqueous solutions 10% by weight of pig gelatin (A), 10% by weight of gum arabic (B), an aqueous dispersion 10% by weight of Fe2Ü3 (Fluka, code Fluka 44955 , composition> 98%) of particles (C) and limonene oil (D) are prepared separately and kept at 50 ° C, in a water bath. In a beaker, at 50 ° C, 15 g of solution (A) are added to 70 g of hot demineralized water, under mechanical shear. The pH is adjusted to 9.1 using 1M NaOH, before adding 5 g of solution (C) and reducing the pH to 4.5 with 1M HCI. Then, 10 g of solution (B) are added to the mixture, followed by the addition of 10 g of oil (D). Mechanical shear is maintained while the solution is left to cool to room temperature. Example 6
    0099 Preparation of hybrid coacervate capsules magnetically sensitive to FesCM inclusions in the coating
    The capsules were made as in Example 5, but with FesCH particles. The resulting capsules could be easily transferred into the bottle in a contact-free manner when a regular magnet purchased from a local supermarket was held and moved against the glass wall of the container.
    权利要求:
    Claims (12)
    [0001]
    1. Process for preparing a hybrid coacervate capsule comprising a) mixing a solution of a first polymer with a dispersion of at least one type of solid particles, at a temperature that is above the gelation temperature of the first polymer, in that the first polymer adsorbes on at least one type of solid particles, to produce a dispersion of particle / polymer complexes; b) adding a solution of a second polymer to the dispersion, in which the second polymer interacts with the particle / polymer complexes, to form hybrid complex coacervates containing particle inclusions; c) adding a core material to the hybrid complex coacervates, in which the hybrid complex coacervates deposit as a coating layer around the active core material / solution interface to form core / coating capsules, each containing the core material. core encapsulated by a hybrid coacervate coating; and d) reducing the temperature of the core / coating capsules to a temperature that is below the gelation temperature of the first polymer; e) optionally, crosslinking of the hybrid coacervate coatings of the capsules; characterized by the fact that the dry matter composition of the hybrid coacervate coating is such that the total mass ratio of solid particles to the total mass of polymers 1 and 2 is between 0.01 and 1.85.
    [0002]
    2. Process according to claim 1, characterized by the fact that the solution of the first polymer is mixed with the dispersion of at least one type of solid particles in conditions sufficient for the first polymer to be adsorbed quickly on at least one type of solid particles.
    [0003]
    3. Process, according to claim 1, characterized by the fact that the pH value and ionic strength of the solution of the first polymer are optimized for the formation of the particle / polymer complexes.
    [0004]
    4. Process according to claim 1, characterized by the fact that the hybrid coacervate has an adequate viscosity which allows the hybrid coacervate to deposit in the core material to form the capsule shell.
    [0005]
    5. Process, according to claim 4, characterized by the fact that the viscosity of the hybrid coacervate is between 100 mPa * s and 2,500,000 mPa * s at a temperature between 30oC and 70oC and at shear rates between 0.01 / se 100 / s.
    [0006]
    6. Process according to claim 1, characterized by the fact that the hybrid coacervate contains two or more types of solid particles.
    [0007]
    7. Core / coating capsule, produced according to the process of claim 1, characterized by the fact that the dry matter composition of the hybrid coacervate wrapper is such that the ratio between the total mass of solid particles and the total mass of the polymers 1 and 2 is between 0.01 and 1.85.
    [0008]
    8. Capsule according to claim 7, characterized by the fact that the casing contains two or more different types of solid particles selected from the group consisting of silicon oxides and other metal oxides, silicates, silver nanoparticles, magnesium silicates and aluminum (clays), leaf silicates (mica), diatomite, perlite, vermiculite, fat crystals, fatty acids or fatty alcohols and their mixtures.
    [0009]
    9. Capsule, according to claim 7, characterized by the fact that the capsule is opaque when hydrated and in which the core is lighter than water, but the capsule settles under gravity or in centrifugal fields.
    [0010]
    10. Capsule according to claim 7, characterized in that the core comprises a solid active ingredient and / or an active liquid ingredient of an oil.
    [0011]
    11. Capsule according to any one of claims 7 to 10, characterized in that the first polymer, polymer 1, is a protein or a polypeptide capable of adsorbing on the surface of the particles to form a new complex that is positively charged or negatively.
    [0012]
    12. Capsule according to any one of claims 7 to 10, characterized in that the second polymer, polymer 2, is a charged non-protein polymer opposite the protein of the first polymer, polymer 1, in the appropriate pH range for coacervation.
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    同族专利:
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    法律状态:
    2018-05-02| B06F| Objections, documents and/or translations needed after an examination request according art. 34 industrial property law|
    2019-07-09| B06T| Formal requirements before examination|
    2020-02-04| B06A| Notification to applicant to reply to the report for non-patentability or inadequacy of the application according art. 36 industrial patent law|
    2020-02-18| B15K| Others concerning applications: alteration of classification|Free format text: AS CLASSIFICACOES ANTERIORES ERAM: A23L 1/00 , A23L 1/22 , A23L 1/226 Ipc: A23L 2/56 (2006.01), A23L 27/00 (2016.01), A23L 27 |
    2020-05-19| B09A| Decision: intention to grant|
    2020-10-20| B16A| Patent or certificate of addition of invention granted|Free format text: PRAZO DE VALIDADE: 20 (VINTE) ANOS CONTADOS A PARTIR DE 23/05/2013, OBSERVADAS AS CONDICOES LEGAIS. |
    优先权:
    申请号 | 申请日 | 专利标题
    EP12169278|2012-05-24|
    EP12169278.4|2012-05-24|
    PCT/EP2013/060619|WO2013174921A1|2012-05-24|2013-05-23|Hybrid coacervate capsules|
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