Methods for preserving active compounds, formulations, and preservatives

Abstract

A method and preservative for storing an active compound are provided, the compound as a powder. The powder is dispersed in an oleogel to form a suspension. The suspension containing the powder in an oleogel network or matrix is ​​formed into microbodies, which are encapsulated by a hydrophilic polymer shell to form microbodies containing the active compound.

Description

Technical Field

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[0001] The present invention relates to a method for preserving active compounds, as well as preservatives and formulations.

[0002] Many active compounds tend to deteriorate when exposed to an oxidizing or humid environment such as ambient air. In particular, hygroscopic compounds can attract moisture and become sticky or even viscous gels or pastes. This can interfere with the handling of the compound and may even increase and / or accelerate its deterioration. Attempts have been made to protect active compounds from such deterioration. A common approach is to enclose the product in an airtight package that has been evacuated and / or flushed with an inert or protective gas. However, when such a package is opened, the product is again exposed to ambient air and thus its storage life is shortened.

[0003] A more sophisticated method for preserving active compounds is described in International Patent Application No. 2022 / 029623 by the applicant. This application describes a process of dissolving a reactive compound in a suitable hydrophilic solvent. The resulting solution is emulsified with a hydrophobic liquid to form microdroplets, and the microdroplets are encapsulated with a hydrophilic polymer shell to form microcapsules. Such preservation has been proven to significantly extend the lifespan of the active ingredient.

Summary of the Invention

[0004] The object of the present invention is to further improve the preservation of reactive compounds by providing alternative preservation processes and preservatives.

[0005] To that end, the present invention provides a method for preserving an active compound, wherein a powder of the active compound is provided, the powder is dispersed in a liquid hydrophobic material that is at least partially gellable or crystallable to form a suspension or dispersion containing the powder, the suspension or dispersion is formed into microbodies, the microbodies are encapsulated by a polymer shell to form microbodies containing one or more cores of the suspension or dispersion, and the microbodies containing the suspension or dispersion are solidified, in particular by gelling and / or crystallizing to form microbodies containing the active compound within at least substantially solidified hydrophobic networks.

[0006] Where used in this application, unless otherwise specified, the term “microbody” may also be interchangeably referred to as “microdroplet,” “microcapsule,” or “microparticle,” and it should be noted that the adjective “micro” refers to a size ranging from submicron, particularly nanoscale, to several millimeters. The descriptor “(partially or completely) solidified, particularly gelled and / or crystallized hydrophobic network” may also be referred to as “oleogel,” and vice versa. Sometimes called organogels, oleogels are gels having a continuous phase of oil. Oleogel networks are characterized by their ability to hold a considerable amount of oil. Oleogels are further characterized by their thermoreversibility, viscoelasticity, and substantial self-supporting properties (under certain conditions). Oleogels may be applied in combination with hydrogels, also called bigels.

[0007] Furthermore, unless otherwise specified, the adjective "micro" refers to dimensions of a few millimeters or less. Therefore, microbodies can have diameters or maximum dimensions ranging from a few micrometers (or microns), particularly tens of micrometers, and especially hundreds of micrometers, to a few millimeters. Due to the relatively small size of microbodies, active compounds can be more readily used as powdered or granular components in a variety of applications, formulations, and products. Powders containing active compounds are trapped inside these anhydrous microbodies, which protect the compounds from the external environment.

[0008] In a further aspect of the present invention, a preservative for an active compound according to the present invention comprises one or more preservative microbodies, each having at least one core surrounded by a shell formed by a polymer network, the core comprising at least a substantially solidified, particularly gelled, gellable or crystallizable liquid hydrophobic material, particularly an oleogel, and a solid powder dispersed throughout the core, the powder comprising the active compound.

[0009] In a further embodiment, the present invention provides formulations comprising an active compound preserved by such a preservative. Such formulations may be used in, or as, cosmetics, personal care or home care products, dermatological products, food or nutritional products, pesticide products, fragrance products, health or wellness products, pharmaceuticals, (bio)medical products, household goods, energy storage products, coating products, or adhesive products.

[0010] As a result, the active compound is dispersed and trapped within a substantially anhydrous, hydrophobic, and airtight environment provided by the oleogel surrounding the core. This appears to significantly improve the shelf life of the compound in question. The core also appears to substantially prevent both the release and dissolution of aqueous and / or hydrophilic solvents, formulations, or powders into the surroundings, which the microbodies may be mixed with. The polymer shell holds the core together, preventing deformation, merging, or damage to the oleogel core and individual microbodies.

[0011] Furthermore, the polymer shell can facilitate handling such as drying, mixing, and / or blending of hydrophobic oleogels, which are used in other formulations such as cosmetics, foods, and pharmaceuticals, including non-oily and hydrophilic formulations, such as aqueous formulations. The polymer shell may be designed to disintegrate or break under induced chemical or mechanical conditions, in which case the active compound, including the powder, is released from the microbody. The active compound remains encapsulated and substantially sealed within the microbody until released, in its previous state.

[0012] The active compound may be released via mechanical and chemical conditions or triggers. Such induced conditions or triggers include, for example, melting, hydrolysis, photodegradation, diffusion, combustion of the oleogel, for example, shear stress such as rubbing on skin or brushing with a paintbrush, for example, to promote acidic or enzymatic degradation or fermentation in the stomach, ileum, colon, or any other part of the digestive tract, for example, compression such as chewing, a combination of shear and compression, extrusion or injection via a small dispenser such as a needle or spray nozzle, for example, chelation, freeze-thaw cycle, or collapse of the core or shell by heating, or any other form of mechanical and / or chemical stress that results in the release of the active compound from the microbodies. The microbodies may be exposed to a solution containing citric acid, where the concentration of the citric acid is 0.01% to 100% by weight, particularly 0.1% to 10% by weight, particularly 0.5% to 5% by weight.

[0013] In certain embodiments, the methods, formulations, and preservatives according to the present invention are characterized in that the shell comprises a polymer network, particularly an interpenetrating network, a double network, and / or a complex of two or more intermolecular or intramolecular crosslinked polymers, more specifically, the polymer network comprises a hydrophilic polymer network, particularly agar, arginate, chitosan, dextran, poly(ethylene glycol), collagen, gelatin, hyaluronic acid, carrageenan, particularly lambda, kappa and Lota carrageenan, fibroin, fibronectin, poly Characterized by comprising one or more polymer electrolytes or polysaccharides selected from l-lysine (PLL), cellulose, graphene, poly(ethyleneimine) (PEI), poly(amidoamine) (PAA), dextran sulfate, silk, silk fibroin, pectin, locust bean gum, gellan gum, guar gum, tragacanth gum, xanthan gum, acacia gum, karaya gum, starch, and sodium carboxymethylcellulose (S-CMC), all of which are naturally derived materials and / or synthetic materials including recombinant proteins and / or derivatives thereof.

[0014] In further embodiments, the methods, formulations, and preservatives according to the present invention are characterized in that the shell comprises a biocompatible, biodegradable, and / or bioabsorbable polymer network, particularly a polymer network comprising methyl-methacrylate derivatives, caprolactone derivatives, lactic acid derivatives, glycolic acid derivatives, and / or copolymers of lactic acid and glycolic acid, and more specifically, the polymer network comprises poly(lactic acid-co-glycolic acid), poly(caprolactone), and / or poly(methyl methacrylate).

[0015] In this regard, particularly successful results have been obtained by further specific embodiments of the methods, formulations, and preservatives according to the present invention, in which the polymer network includes a crosslinked or interpenetrating arginate network, in particular a calcium crosslinked arginate network. The network can be further enhanced by incorporating nanoparticles or microparticles and / or polymer electrolytes.

[0016] In certain embodiments, the methods, formulations, and preservatives according to the present invention are characterized in that the polymer shell comprises an arginate network, particularly a sodium, calcium, and / or shellac-reinforced arginate network.

[0017] In further specific embodiments, the methods, formulations, and preservatives according to the present invention wherein the liquid hydrophobic material comprises at least one oil, particularly, - Vegetable oils, such as sunflower oil, corn oil, linseed oil, canola oil, castor oil, palm oil, coconut oil, avocado oil, sweet almond oil, calophyllum oil, sesame oil, olive oil, jojoba oil, soybean oil, cottonseed oil, rapeseed oil, peanut oil, linseed oil, borage oil, safflower oil, macroalgae oil and seaweed oil, - Essential oils, ether oils, macerated oils, triglycerides, - Animal oils, such as animal fat, lanolin and marine oils, such as fish oil, - Synthetic oils, and - Neutral oils such as medium-chain triglyceride oils and mixtures or derivatives thereof, more specifically non-toxic and easy-to-use oils, especially sunflower oil or safflower oil. It is characterized by containing one or more oils from the group including the following.

[0018] In particular, the method, preservative, or formulation according to the present invention may be characterized in that the liquid hydrophobic material contains sunflower oil or safflower oil. More specifically, the method, preservative, or formulation according to the present invention may be characterized in that the liquid hydrophobic material is an oleogel containing oil, particularly sunflower oil or safflower oil.

[0019] In further specific embodiments, the method, preservative or formulation according to the present invention is characterized in that the liquid hydrophobic material is an oleogel containing an oil, more specifically an oil having an oleic acid content of more than 10%, more specifically more than 25%, more specifically more than 50%, and more specifically more than 70%, and more specifically a high-oleic sunflower oil characterized by an oleic acid content of more than 70%.

[0020] The oleogel may contain an oil gelling agent in a concentration of at least 1% by weight (relative to the weight percentage of the oleogel), particularly at least 2% by weight, particularly at least 3% by weight, particularly at least 4% by weight, particularly at least 5% by weight, particularly 1% to 10% by weight, and particularly 4% to 6% by weight.

[0021] In particular, the method, preservative or formulation according to the present invention is characterized in that the oleogel retains a considerable amount of the oil, and more specifically, the oleogel may be characterized in that it has the ability to bind or retain more than 90%, particularly more than 95%, of the oil in the oleogel for at least four weeks at room temperature, particularly 40°C.

[0022] The ability of the oleogel to bind the oil is also called the "oil-binding capacity," and is, for example, equal to the weight of the bound oil, measured after centrifuging the oil / oleogel mixture, divided by the weight of the solid fat, measured, for example, by pulsed nuclear magnetic resonance (NMR). Alternatively, the stability of the oil-binding capacity can be determined by separating the unbound oil phase from the oleogel over time and determining the weight and / or volume ratio of the unbound oil to the oleogel.

[0023] In various markets, ether oils, macerated oils, and / or essential oils or waxes further add desirable soothing sensory properties or therapeutic benefits to products. Examples of suitable organic lipophilic compounds include, for example, immortelle, lavender, German chamomile, neroli, peppermint oil, rosemary, rose oil, tea tree oil, pine needle oil, juniper berry, roasted chestnut extract, birch leaf extract, hay seed extract, ethyl acetate, camphor, menthol, rosemary extract, eucalyptus oil, and cranberry oil.

[0024] In further specific embodiments, the methods, formulations, and preservatives according to the present invention are characterized in that the liquid hydrophobic material comprises at least one hydrophobic gelling agent, specifically a fatty acid, wax, or sterol, which is provided in liquid form and is gelled, crystallized, or solidified to form the microbodies. Thus, the liquid material is processed in a liquid state and solidified at a temperature below the gelling temperature of the hydrophobic gelling agent to form crystals incorporated into a hydrophobic network, also known as an oleogel. The suspended powder is trapped in such a stable solidified oleogel matrix, preventing migration and / or phase separation of the suspension.

[0025] In this regard, the liquid hydrophobic material may particularly include one or more fatty acids and / or waxes from the group comprising paraffin wax, rice bran wax, sunflower wax, carnauba wax, candelilla wax, beeswax, microcrystalline wax, coconut wax, ozocerite wax, beta-sitosterol, gamma-oryzanol, stearic acid, palmitic acid, behenic acid, myristic acid, lauric acid, capric acid, and fatty acid derivatives, such as isopropyl myristate, isopropyl palmitate, isopropyl stearate, and dibutyl adipate, which are fatty acid esters having short-chain alcohols, and carnauba wax in particular.

[0026] The gelling, gelation, melting or crystallization temperatures of an oleogel and / or a hydrogel, all together and also separately, are also collectively called the solidification temperature, and typically may not be a single point, but may occur over a temperature range characterized by onset and offset temperatures, or specifically, melting onset and melting offset temperatures, gelation onset and gelation offset temperatures, or crystallization onset and crystallization offset temperatures. Note that "onset" refers to the start of each process and "offset" refers to the completion of each process. Also note that the solidification temperature of a liquid material may be lower than the melting / crystallization temperature, in other words, the crystallization offset temperature may be lower than the crystallization onset temperature. It should also be noted that the expressions "gelation" and "solidification", as well as similar derivatives such as "gelated", "gelating" and "solidified", can be used interchangeably.

[0027] In a further specific embodiment, the method, formulation and preservative according to the invention are characterized in that the oleogel comprises one or more gelling agents selected from the group consisting of hydrophilic gelling agents, particularly polysaccharides, (modified) starch, proteins, natural gums, hydrocolloids, steroids, hydrophilic phytosterol derivatives, or phospholipids, particularly cellulose, maltodextrin, dextran, hyaluronic acid, gelatin, whey protein, gum arabic, tragacanth gum, xanthan gum, carrageenan, agar, lecithin, propylene glycol, silica (nanoparticles), and more specifically ethylcellulose. The hydrophilic gelling agent helps to further stabilize the suspension of the powder and the oleogel.

[0028] Generally, fats, waxes, and oleogels are solid or creamy (malleable) at room temperature. This natural property of fats, waxes, and oleogels can be utilized to further immobilize active compounds within capsules. Thus, a further specific embodiment of the method according to the invention is characterized in that the liquid hydrophobic material is processed in the liquid state and at least partially solidifies or has solidified at a temperature lower than its solidification temperature. In a further specific embodiment, the method according to the invention is characterized in that the liquid hydrophobic material is cooled at a cooling rate faster than 0.1 K / min, particularly faster than 1 K / min, more specifically faster than 10 K / min, and even more specifically faster than 100 K / min to a temperature lower than its solidification temperature.

[0029] The solidification temperature of the liquid material can be adjusted by varying its composition, particularly the type and concentration of the oil, wax, and other components in the oleogel. Oleogels containing these waxes or fats can be processed in liquid form to produce microbodies or capsules using the method of a co-pending European patent application by the same applicant as the applicant who published as European Patent No. 3,436,188 (A1), the subject matter of which is incorporated herein by reference.

[0030] Subsequently, the product may be stored at a temperature lower than the gelation temperature of the oleogel, which can be, for example, 40 °C, room temperature, or 4 °C depending on the oleogel composition. The oleogel contained in the capsule, while in a solid state, hinders both the movement of the active compound out of the capsule and the movement of environmental compounds into the capsule. Storing the microbodies at a temperature lower than the solidification temperature of the oleogel can also result in a denser oleogel network and further strengthening of the oleogel network over time.

[0031] The oleogel composition according to the present invention may have an oleogel solidification temperature of 0°C to 100°C, particularly 4°C to 90°C, particularly 4°C to 40°C, particularly 20°C to 40°C, particularly 20°C to 90°C, particularly 40°C to 90°C, particularly 40°C to 50°C, particularly 50°C to 60°C, particularly 60°C to 70°C, particularly 80°C to 90°C, and preferably a temperature above room temperature.

[0032] Preferably, the liquid state is achieved without adversely affecting the integrity of the active compound. For this purpose, further embodiments of the methods, formulations, and preservatives according to the present invention are characterized in that the oleogel has a solidification offset temperature of less than about 60°C. This suppresses heat-induced degradation of the active compound. Suitable candidates for formulation of the oleogel are waxes selected from the group consisting of, for example, montan wax, carnauba wax, glycol montanate, paraffin wax, rice bran wax, sunflower wax, candelilla wax, beeswax, microcrystalline wax, coconut wax, ozocerite wax, and mixtures thereof.

[0033] In further specific embodiments, the methods, formulations, and preservatives according to the present invention are characterized in that the oleogel comprises an emulsifier or plasticizer, such as fatty acids, glycolipids, monoglycerides, diglycerides, triglycerides, or phospholipids, or mixtures thereof, particularly soy lecithin or polyglycerol polyricinoleate (PGPR).

[0034] In further specific embodiments, the methods, formulations, and preservatives according to the present invention are characterized in that the oleogel contains an oil-soluble antioxidant, such as tocopherol (known as vitamin E), particularly alpha-tocopherol, particularly 0.01 to 10% by weight of alpha-tocopherol in the oleogel, and particularly 0.1 to 1% of alpha-tocopherol in the oleogel.

[0035] In further specific embodiments, the methods, formulations, and preservatives according to the present invention are characterized in that the powder is provided as a dry, substantially water-free powder. Removing initial water or water vapor extends the lifespan of the powdered component.

[0036] In further specific embodiments, the methods, formulations, and preservatives according to the present invention are characterized in that the powder comprises one or more antioxidants and / or nutrients, particularly catalase, polyphenols, curcumin, quercetin, catechin, lignan, resveratrol, citric acid, and L-ascorbic acid. In particular, the powder comprises L-ascorbic acid. The encapsulation according to the present invention protects the compound from oxidizing and / or promoting oxidation conditions such as moisture and oxygen from the ambient air, or from the mixed liquid formulation, thereby retaining at least a substantial portion of its original nutrients and / or antioxidant capacity compared to antioxidants and / or nutrients that are not encapsulated.

[0037] In further specific embodiments, the methods, formulations, and preservatives according to the present invention are characterized in that the active compound is a wettable powder, particularly hyaluronic acid, arginate, gelatin, or collagen. The encapsulation according to the present invention substantially shields the compound from ambient air and / or water, thereby preventing the decomposition of the wettable powder by hydrolysis, for example, and thereby preserving its original structure and hydration capacity.

[0038] Furthermore, microbodies containing a water-impermeable oleogel advantageously allow for the encapsulation of relatively high concentrations of hygroscopic compounds, such as hydrophilic polymers like dry hyaluronic acid powder. In such an environment, the hygroscopic compound remains a dry, non-wet powder, which may be blended within the molten oleogel during the encapsulation process, enabling simpler handling and easier encapsulation of higher polymer concentrations compared to handling hygroscopic compounds that are not mixed with the oleogel.

[0039] Specifically, hydrophilic polymers, particularly those with relatively high molecular weights (>100 kDa, >1000 kDa) and / or high water-binding molecules such as high molecular weight hyaluronic acid, can become known to be sticky and viscous when interacting with water or moisture. Sticky powders or highly viscous solutions are difficult to process and particularly difficult to encapsulate. However, in further specific embodiments, the methods, formulations, and preservatives of the present invention are characterized in that the powder comprises a hydrophilic polymer having a molecular weight greater than 10 kDa, particularly greater than 100 kDa, and particularly greater than 1000 kDa, especially polysaccharides, especially hyaluronic acid. The present invention makes it possible to encapsulate such relatively high concentrations of hygroscopic compounds by dispersing them in the form of a dry powder within an oleogel and substantially protecting them from contact with water or other aqueous solvents.

[0040] In further specific embodiments, the methods, formulations, and preservatives according to the present invention are characterized in that the powder comprises hygroscopic compounds, particularly natural compounds, particularly natural compounds from the group consisting of hydrophilic polymers, polysaccharides, proteins, nucleic acids, and water-soluble salts.

[0041] In another specific embodiment, the method, formulation and preservative according to the present invention is characterized in that the powder comprises one from the group consisting of hygroscopic salts, particularly salts of quaternary ammonium cations, more specifically choline salts, particularly choline chloride, choline tartrate, choline borate, choline dihydrogen citrate, choline bicarbonate and choline carbamate, and even more specifically choline chloride.

[0042] Choline salts are used in nutrition, for example, as supplements in animal and poultry feed. In such cases, the hygroscopic nature of commonly available choline salts makes uniform mixing difficult, resulting in unsatisfactory preparations. Furthermore, due to the hygroscopic nature found in most choline salts, the salts tend to liquefy, which poses a problem during processing and also causes undesirable odors in the material. By mixing dried choline salts into a liquefied oleogel and subsequently encapsulating them in preservation microbodies according to the present invention, choline is protected from hygroscopicity, clumping, and degradation.

[0043] In another specific embodiment, the method, formulation and preservative according to the present invention comprises a dried, spray-dried or freeze-dried composition comprising a drying excipient for the active ingredient (hygroscopic), particularly a drying excipient comprising at least one polycarbohydrate, monosaccharide, disaccharide or polysaccharide compound, more specifically a drying excipient that is a sugar, more specifically a drying excipient selected from the group consisting of dextran, dextrin, maltodextrin, trehalose, lactose, glucose, dextrose, sucrose, fructose, maltose, isomaltose, sorbitol, mannitol, lactitol, xylitol and / or erythritol.

[0044] In further specific embodiments, the methods, formulations, and preservatives according to the present invention are characterized in that the powder comprises a biological compound, in particular an organism, a protein, an enzyme, a peptide, a nucleotide, or a mixture thereof.

[0045] In further specific embodiments, the methods, formulations, and preservatives according to the present invention are characterized in that the powder comprises viable compounds, in particular living cells, more specifically bacteria or microbiota.

[0046] In further specific embodiments, the methods, formulations, and preservatives according to the present invention are characterized in that the powder comprises one or more susceptible bacteria selected from the group consisting of anaerobic bacteria, non-spore-forming bacteria, and other bacteria sensitive to moisture, acid, heat, and / or oxygen.

[0047] In a further aspect of the present invention, the preservation microbodies at least partially protect the susceptible bacteria, thereby increasing the viability of the bacteria during and / or after the manufacturing process and / or extending the shelf life of the product. In other words, when the active compound, in particular the susceptible bacteria, is encapsulated within the preservation microbodies, the active compound, in particular the susceptible bacteria, is more stable and has a higher viability during and after the manufacturing of the product compared to the active compound, in particular the susceptible bacteria, not encapsulated within the preservation microbodies.

[0048] In further specific embodiments, the methods, formulations, and preservatives according to the present invention include a powder containing one or more bacteria from the group consisting of Bacteroides, Bifidobacterium, Fusobacterium, Bacillus, Lactobacillus, Saccharomyces, Streptococcus, Enterococcus Porphyromonas, Prevotella, Actinomyces, Propionibacterium, and Clostridium, particularly Bifidobacterium bifidum and Bifidobacterium lactis. Lactobacillus lactis), Bifidobacterium adolescentis, Bifidobacterium breve, Bifidobacterium infantis, Bifidobacterium longum, Lactobacillus acidophilus, Lactobacillus rhamnosus, Saccharomyces boulardii, Lactobacillus plantarum, Streptococcus thermophilus, Lactobacillus casei, Lactobacillus paracasei Lactobacillus paracasei, Lactobacillus reuteri, Lactobacillus fermentum, Bacillus coagulansIt is characterized by containing one or more bacteria from the group consisting of Bacillus coagulans, Bacillus subtilis, and Enterococcus faecium.

[0049] In further specific embodiments, the methods, formulations, and preservatives according to the present invention include a powder containing one or more anaerobic bacteria from the group consisting of Bacteroides, Bifidobacterium, Fusobacterium, Porphyromonas, Prevotella, Actinomyces, Propionibacterium, and Clostridium, particularly Bifidobacterium bifidum, Bifidobacterium lactis, Bifidobacterium adolescentis, and Bifidobacterium breve. It is characterized by containing one or more anaerobic bacteria from the group consisting of Bifidobacterium breve, Bifidobacterium infantis, and Bifidobacterium longum.

[0050] In further specific embodiments, the methods, formulations, and preservatives according to the present invention are characterized in that the powder comprises one or a so-called “next-generation probiotic,” more specifically, the powder comprising Akkermansia muciniphila, Faecalibacterium prausnitzii, Bacteroides thetaiotaomicron, Bacteroides fragilis, Roseburia spp., Prevotella spp., Aristipes spp., Christensenella minuta, Blautia spp., and Eubacterium halley. It is characterized by containing one or more next-generation probiotics from the group consisting of hallii and Methanobrevibacter smithii.

[0051] In further specific embodiments, the methods, formulations, and preservatives according to the present invention are characterized in that the powder comprises one or more prebiotics, particularly one or more prebiotics from the group consisting of oligosaccharides, fructans, galactans, starches, pectin, and beta-glucans. Prebiotics are also called dietary fiber.

[0052] In a further specific embodiment, the method according to the present invention is characterized in that the liquid hydrophobic material is solidified by combining a phase having a temperature lower than the solidification temperature of the liquid hydrophobic material, in particular a temperature lower than room temperature, and more specifically a temperature of less than 10°C, in particular a liquid phase and microbodies.

[0053] In further specific embodiments, the method according to the present invention is characterized in that the phase comprises a liquid phase containing a crosslinking compound for crosslinking the shell polymer. These microbodies can be encapsulated by combining a liquid flow containing the crosslinking compound with a flow of the microbodies, by using a method of a concurrently pending European patent application, the subject matter of which is incorporated herein by reference, published in particular as European Patent No. 3,436,188(A1) by the applicant.

[0054] In a further specific embodiment, the method according to the present invention is characterized in that the liquid phase has a temperature that induces at least one thermal or physical crosslinking of the shell polymer.

[0055] The microbodies can be stored in the carrier solution at a temperature higher than the freezing temperature of the carrier solution and lower than the oleogel solidification temperature, particularly below room temperature, especially below 10°C, and especially around 4°C.

[0056] In further specific embodiments, the methods, formulations, and preservatives according to the present invention are provided in which the powder is a catalyst, particularly - In particular, compounds that catalyze amino crosslinking, including p-TSA (para-toluenesulfonic acid), DNNDSA (dinonylnaphthalene disulfonic acid), DDBSA (dodecylbenzenesulfonic acid), DNNSA (dinonylnaphthalene monosulfonic acid), phosphoric acid, and carboxylic acids, or - Compounds that catalyze urethane crosslinking, particularly DBTL (dibutyltin laurate), DOTL (dioctyl laurate), DBTO (dibutyltin oxide), bismuth-based catalysts, zirconium-based catalysts, and amine-based catalysts. It is characterized by containing one or more compounds from the group consisting of the following.

[0057] In a further specific embodiment, the method according to the present invention is characterized in that the one or more microbodies contain the hydrophobic compound by immersing the one or more microbodies in a solution, particularly a concentrate, of the hydrophobic compound, thereby allowing the hydrophobic compound to diffuse through the shell into the one or more cores of the one or more microbodies.

[0058] In a further specific embodiment, the method according to the present invention provides one or more microbodies having one or more cores in a molten state, then immerses the one or more microbodies in a solution, particularly a concentrate, of the hydrophobic compound, allowing the hydrophobic compound to diffuse into the one or more cores of the one or more microbodies in a molten state, and subsequently solidifies the one or more cores at least substantially, thereby incorporating the hydrophobic compound into the one or more microbodies. The cores may, for example, contain molten oil or wax. After such cores are solidified again, for example by re-gelling, the hydrophobic compound is trapped within the microbodies.

[0059] In more specific embodiments, the method according to the present invention is characterized in that the shell comprises a calcium arginate network, which is weakened or completely removed before or during final application, particularly by scavenging calcium ions and at least partially destroying the calcium arginate network of the shell, more specifically by introducing a chelating agent such as citrate or ethylenediaminetetraacetic acid (EDTA).

[0060] In a further specific embodiment, the method according to the present invention is characterized in that the microbodies are dried by a drying method selected from the group including evaporation, blowing of a drying gas, vacuum drying, fluidized bed drying, freeze-drying, microwave drying, and chemical drying. Such a method removes water from the microbodies, particularly from the hydrophilic shell. In a further specific embodiment, the dried or dehydrated microbodies are formed in at least a portion of the fluidized powder.

[0061] In further specific embodiments, the methods, formulations, and preservatives according to the present invention are characterized in that the active ingredient has a functional property that is masked by the at least one core within the microbody. The functional property may relate to either taste or smell. In specific embodiments, the active ingredient is a fragrance, a scent, or a mixture of odor-producing compounds.

[0062] In another specific embodiment, the active ingredient is a mixture of flavor or taste compounds. In yet another specific embodiment, the active ingredient is a tasteless and / or odorous compound, the taste and / or odor of which is at least partially masked by the method, formulation and / or preservative according to the present invention.

[0063] In further embodiments, formulations containing an active compound preserved by a preservative according to the present invention are characterized by being products or intermediate products for cosmetic, dermatological, food, nutritional, supplementary, pesticide, fragrance, pharmaceutical, (bio)medical, household, energy storage, coating, or adhesive / glue applications. More specifically, the formulation or (intermediate) product is detrimental to the initial (i.e., unpreserved) active compound, and more specifically, the formulation or (intermediate) product contains a substantial amount of water, more specifically >30% by weight of water, and more specifically >50% by weight of water. More specifically, the formulation or (intermediate) product is detrimental to the initial (i.e., unpreserved) active compound, and more specifically, the formulation or (intermediate) product has an acidic pH < 7, more specifically pH < 4. More specifically, the product is selected from the group consisting of creams, lotions, serums, gels, shampoos, beverages, drinks, carbonated drinks, gummies, bars, tablets, capsules, pills, dairy products, and injections.

[0064] In further embodiments, a formulation containing an active compound preserved by a preservative according to the present invention is a product or intermediate product produced by a process that damages or harms the active compound (especially when the active compound is not in the preserved state), more specifically, the process comprises one or more process steps carried out at room temperature or above, more specifically 40°C or above, more specifically 60°C or above, more specifically 80°C or above, more specifically, one or more process steps relating to spray drying, hot melt, extrusion, injection molding, more specifically, the process comprises one or more steps involving shear forces (e.g., mixing, blending, injection, extrusion, or centrifugation), more specifically, the process relates to the production of (edible) gummies, also known as gummy candy.

[0065] The present invention further relates to cosmetics, personal care products or home care products, dermatological products, food or nutritional products, pesticide products, fragrance products, health or wellness products, pharmaceuticals, (bio)medical products, household goods, energy storage products, coating products, and adhesive products, and includes formulations having the above-mentioned active compounds in a preserved form. Some of these will be described in more detail with reference to several embodiments. The present invention will be described in further detail below with reference to specific embodiments and accompanying drawings. In the figures, the following applies: [Brief explanation of the drawing]

[0066] [Figure 1] Figure 1 shows exemplary images of phase separation in LAA-containing oleogels with different wax fractions. [Figure 2] Figure 2 shows the quantification of the phase separation shown in Figure 1. [Figure 3] Figure 3 shows a visual view of multiple capsules mixed with an aqueous base liquid. [Figure 4] Figure 4 shows a schematic diagram of microdroplets encapsulated by a polymer shell according to the present invention. [Figure 5] Figure 5 is a graph showing the viable and proliferating probiotic cells expressed in colony-forming units (CFUs) per gram of the original excipient material at 1, 5, and 13 weeks, respectively, in a stability test comparing unencapsulated probiotics in water at 25°C with unencapsulated probiotics exposed to ambient air (ND indicates undetectable). [Figure 6]Figure 6 shows a graph comparing the time-dependent stability of the encapsulated probiotic Lactobacillus rhamnosus during accelerated stability testing for the following core formulations: PB Beads 1: Probiotic powder directly dispersed in oleogel with 5% carnauba oleogel in safflower oil at 45°C; PB Beads 2: Probiotic powder mixed in a 1:1 ratio in oleogel with 5% carnauba oleogel in safflower oil at 50°C; PB Beads 3: Probiotic powder directly dispersed in oleogel with 5% candelilla oleogel in safflower oil at 45°C. Surviving and proliferating probiotic cells are expressed as colony-forming units (CFU) per gram of the original excipient material after 13 weeks of stability testing. The encapsulated probiotics were incubated in water at 25°C and extracted from the capsules at specified time points. [Figure 7] Figure 7 is a graph showing the relative antioxidant activity of encapsulated active LAA versus unencapsulated active LAA over time under different stability test conditions.

[0067] Please note that the drawings are merely illustrative and not necessarily to scale. In particular, certain dimensions may be more or less exaggerated to help to clarify any particular feature. Similar parts are generally indicated by the same reference number throughout the drawings. [Modes for carrying out the invention]

[0068] Figure 4 shows a schematic diagram of a preservative according to the present invention. The preservative comprises one or more microbodies shown in the figure, encapsulated by a polymer shell according to the present invention. The microbodies comprise cores 10, 20 surrounded by a shell 30. The shell 30 is formed by a polymer network. The cores 10, 20 comprise at least a substantially solidified, particularly gelled, gellable or crystallizable liquid hydrophobic material 20, particularly an oleogel. The solid powder 10 is dispersed throughout the oleogel 20 and comprises the active compound.

[0069] In principle, the microbodies or microdroplets according to the present invention can be realized in a wide range of dimensions, from submicron-like nanoscales to several millimeters. The application of active compounds has been found to be particularly preferred when provided in the form of such micro or nanomicrobodies having sizes ranging from submicron to millimeters. Thus, the shell layer 30 can enclose volumes ranging from about 1 femtoliter to about 1 to several milliliters. Similarly, the microdroplets 10, 20, and 30 have diameters of approximately 0.5 microns to 1 centimeter, particularly 5 microns to 5 millimeters, particularly 100 to 500 microns, and more specifically 150 to 350 microns, 500 to 5000 microns, 1 to 5 millimeters, or 2 to 4 millimeters.

[0070] Microbodies may be substantially spherical and have a sphericity greater than 0.8, particularly greater than 0.9, and more specifically greater than 0.95. However, microbodies or microdroplets do not have to be perfectly spherical, and their diameter is represented by their average Ferret diameter, determined, for example, using microscopic or macroscopic imaging combined with dynamic or static image analysis. Alternatively, the diameter may be determined using laser diffraction, dynamic ultrasonic extinction, or dynamic light scattering.

[0071] When measured using non-3D microscopy techniques, for example, using standard bright-field or phase-contrast microscopy, the sphericity of a microbody can be described as roundness. In this case, the microbody may be substantially circular and have a roundness greater than 0.8, especially greater than 0.9, and more specifically greater than 0.95.

[0072] The sphericity of a particle can be calculated by (π^1 / 3(6Vp)^2 / 3) / Ap [where Vp is the volume of the particle and Ap is the surface area of ​​the particle, and a perfect sphere is evaluated with a sphericity of exactly 1]. The circularity of a particle can be calculated by 4π(area / perimeter^2), where a perfect circle is evaluated with a circularity of 1.

[0073] Preferably, the microbodies have substantially the same size within a size distribution (degree of variance) that exhibits a relative size distribution characterized by a coefficient of variation (i.e., standard deviation divided by mean) of less than 10%, particularly less than 7.5%, and more specifically less than 5%. A relative size distribution of less than 10% is called a "simple variance".

[0074] The suspension 20 may contain the powder 10 at concentrations of more than 0.01% by weight / weight (wt%), particularly more than 1% by weight, particularly more than 10% by weight, particularly 0.01 to 65%, particularly 0.1 to 50% by weight, particularly 0.5 to 5% by weight, particularly 5 to 40% by weight, particularly 5 to 15% by weight, and particularly about 10% by weight. The water content of the suspension may be less than 40%, particularly less than 30%, particularly less than 20%, and particularly less than 10%.

[0075] The water content of the suspension may be less than 40%, particularly less than 30%, particularly less than 20%, and particularly less than 10%. The water activity (aw) of the oleogel may be less than 0.7, particularly less than 0.6, particularly less than 0.5, particularly less than 0.4, particularly less than 0.3, particularly less than 0.2, and particularly less than 0.1. Water activity (aw) is calculated by dividing the partial pressure of water vapor in the solution by the partial pressure of water vapor at standard conditions. The water activity (aw) of the oleogel may be less than 0.7, particularly less than 0.6, particularly less than 0.5, particularly less than 0.4, particularly less than 0.3, particularly less than 0.2, and particularly less than 0.1.

[0076] Example 1: To prepare the oleogel, sunflower oil was heated to 100°C and carnauba wax flakes were added while stirring. Once the wax flakes were completely dissolved, the molten wax / oil mixture was left at 100°C for 10 minutes, and then cooled to 40°C. Ultrafine L-ascorbic acid (LAA) powder was added (partially) to the liquid wax / oil mixture while stirring to prepare a suspension. The suspension was placed in an ultrasonic bath maintained at 40°C for 45 minutes in sweep mode to further promote the uniform dispersion of the LAA powder. The homogenized LAA / wax / oil suspension was then gelled, and the suspension was incubated at 4°C for at least 1 hour to form an LAA-containing oleogel.

[0077] The stability of the LAA-containing oleogel systems was determined by measuring the relative amount of phase separation after incubation at 40°C and humidity >80% for 28 days. For comparison, the carnauba wax concentrations were 2.5 wt% (A), 3.5 wt% (B), 4.5 wt% (C and D), and 5.5 wt% (E) in sunflower oil. The LAA concentration varied from 10 wt% to 40 wt% in the oleogel. Figure 1 (representative image) and Figure 2 (quantification of phase separation) clearly show that suspensions B-E containing more than 3 wt% wax were significantly more stable than suspension A containing less than 3 wt% wax after 28 days at 40°C and humidity >80%.

[0078] Example 2: To prepare the oleogel, 340g of sunflower oil was heated to 100-110°C, and then 20g of candelilla wax was added. The mixture was stirred until the wax melted, and then maintained at 100-110°C for 10-15 minutes. The mixture was cooled to 60°C while stirring. Then, 40g of LAA was slowly added to the wax / oil mixture while stirring at 2500 rpm using an overhead stirrer.

[0079] After adding the LAA, the mixture was stirred at 2500 rpm for at least 5 minutes, followed by 2000 rpm for 15 minutes, while maintaining the temperature at 50°C–60°C. Then, to prevent the temperature from rising above 60°C, the LAA / wax / oil mixture was further homogenized using a rotor-stator mixer (ultra-turrax) at 16000 rpm for 5 minutes with 1–2 minute mixer intervals. During the homogenization intervals, the mixture was continuously mixed by gentle stirring to maintain a uniform suspension. The LAA / wax / oil suspension was kept at 50–60°C at all times, and until further use (i.e., encapsulation). Capsules were manufactured using a dispensing device with two syringe pumps and a coaxial nozzle containing an inner channel surrounded by a coaxially mounted annular outer channel.

[0080] A syringe preheated to at least 50°C was filled with an LAA / wax / oil suspension and connected to the core ring of a coaxial nozzle via a heat trace pipe (set to at least 50°C). Another syringe (similarly preheated to at least 50°C) was filled with an aqueous solution containing 0.75 wt% sodium alginate (SA), 0.5 wt% agar, and 0.5 wt% carboxymethylcellulose (CMC) and connected to the outer ring of a coaxial nozzle via a heat trace pipe (set to at least 50°C).

[0081] The syringe was emptied using a syringe pump to create a steady flow of a mixture exiting a coaxial nozzle and pinching off into compound core-shell micro-cobodies containing a core of LAA / wax / oil suspension and a shell of SA / agar / CMC solution. The micro-cobodies, falling (by gravity), were collected in an ice-cooled, continuously stirred bath containing a crosslinking agent solution with 0.2 M calcium chloride and 20 v / v% ethanol. After incubation for at least 15 minutes, the crosslinked capsules were transferred to a crosslinking agent solution (without ethanol) containing calcium chloride and stored overnight at 4°C, thereby further gelling the oleogel core.

[0082] Example 3: Alternative capsule manufacturing methods were investigated using similar core and shell liquids (i.e., 20% LAA / 5.0% carnauba wax in a sunflower oil suspension as the core liquid, and 0.75% SA / 0.5% agar solution as the shell liquid). Specifically, capsules were manufactured using the "airborne microfluidic technique" described in International Publication No. 2017 / 167798, which uses a heat-traced coaxial first nozzle and a simple (single-opening) second nozzle set to at least 50°C. The core and shell liquids were injected from the heated coaxial nozzle while a crosslinking agent solution containing 0.2M calcium chloride + 20 v / v% ethanol was injected from the second nozzle.

[0083] By vibrating a coaxial nozzle using an external actuator device driven by a waveform generator that, in combination with a signal amplifier, produces a sine wave with a frequency of 100 Hz, the liquid core / shell composite jet (having an active ingredient / oil / wax dispersion in the core and a hydrophilic polymer solution in the shell) was divided into substantially identical micro-clobodies. Such monodisperse composite droplet trains or jets can typically be composed of substantially equal-sized micro-clobodies, each having a coefficient of variation in size or diameter of typically less than 10%, i.e., the standard deviation divided by the mean.

[0084] A compound core-shell micro-clobody flow (at approximately 50°C to 60°C) was combined with a liquid jet containing a crosslinking agent maintained at approximately 4°C. This caused (partial) solidification of the shell by crosslinking the polymer in the shell (physically or chemically), thereby forming SA / agar / CMC capsules with a core containing dried LAA powder suspended in a gelling oil / wax mixture. The combined micro-clobody and jet were recovered in a bath containing an ice-cold crosslinking agent solution with 20% ethanol and 0.2M calcium chloride. Some capsules were post-treated with 1% by weight citric acid, which not only crosslinks the CMC but also acts as a plasticizer for the calcium-arginate polymer network, increasing the overall mechanical stability and yield strength of the capsules. The resulting capsules were mixed with another aqueous phase, and the stability of the product was analyzed by evaluating the appearance and color of the samples at several points during accelerated stability tests at 40°C and 60°C and humidity >80%.

[0085] Figure 3 shows visual aspects of several capsules mixed with an aqueous base solution after a 28-day accelerated stability test (40°C and humidity >80%). The sample on the left (Figures 3A and 3B) contains a capsule having a shell containing calcium-crosslinked sodium alginate and a core containing 10% by weight of dry LAA powder dispersed in an oleogel consisting of 5% by weight of carnauba wax in sunflower oil. The sample on the right (Figures 3C and 3D) contains a capsule having a shell containing calcium-crosslinked sodium alginate similar to the capsule in the sample on the left, and a core containing a carnauba wax-stabilized W / O emulsion containing 10% LAA dissolved in the aqueous phase. These capsules (Figures 3C and 3D) were prepared according to the method and design described in International Patent Application No. 2022 / 029623 by the present applicant.

[0086] From the images, it can be clearly observed that both the capsule and the aqueous buffer surrounding the capsule in the left sample (Figures 3A and 3B), prepared according to the present invention, are significantly less discolored than the capsule and the aqueous buffer surrounding the capsule in the right sample (Figures 3C and 3D). Since LAA degradation leads to discoloration, these data indicate that the method and storage microbodies according to the present invention result in better preservation of the active ingredient compared to the method and storage microcapsules described in International Publication No. 2022 / 029623.

[0087] Example 4: The capsules were prepared in the same manner as in Example 3, but with different core and shell solutions. Instead, the core composition contained 1% by weight of probiotics (spray-dried powder containing a mixed strain) suspended in a mixture of 4% by weight of candelilla wax in sunflower oil, rather than LAA in a carnauba wax / sunflower oil mixture.

[0088] Example 5: Capsules were prepared in the same manner as in Example 3, but with different core and shell solutions. The core composition contained 2% by weight of non-spore-forming probiotics (lyophilized Lactobacillus rhamnosus) suspended in a mixture of 5% by weight of carnauba wax in safflower oil, instead of LAA in a carnauba wax / sunflower oil mixture, and the shell contained 1.5% by weight of SA instead of SA / agar mixture.

[0089] After manufacturing, capsules containing probiotics were subjected to stability testing, during which time they were incubated in a calcium-containing aqueous medium at 25°C. At predetermined time points (1, 5, and 13 weeks later), probiotics were extracted from the capsules using shear homogenization, seeded onto agar plates, and incubated at 37°C for 48 hours. The number of viable and probiotic cells was assessed by counting colony-forming units (CFUs).

[0090] Samples were prepared in pairs and seeded using technical replicates. Each control contained, respectively, unencapsulated probiotic powder incubated in a calcium-containing aqueous medium and unencapsulated probiotic powder incubated in ambient air with a relative humidity of approximately 40–50%. Survival analysis (i.e., CFU count) showed that encapsulation of probiotics in capsules according to the present invention significantly improved the survival rate of probiotics compared to the unencapsulated counterpart under time-dependent stability test conditions (Figure 5).

[0091] After 5 weeks of incubation, the probiotics in water were observed to be unviable (i.e., no detectable CFU), and by week 13, all probiotics exposed to air had died, while the encapsulated probiotics remained viable. These findings suggest that the encapsulated formulation according to the present invention provides protective properties against water, moisture, and uncooled (i.e., heat) conditions, which are important factors known to impair the viability of probiotics.

[0092] Example 6: Bygel capsules were prepared in the same manner as in Example 3, but with different core and shell solutions. The core composition contained 2% by weight of non-spore-forming probiotics (lyophilized Lactobacillus rhamnosus) suspended in a mixture of 5% by weight of carnauba wax in safflower oil, instead of LAA in a carnauba wax / sunflower oil mixture, and the shell contained 1.5% by weight of SA instead of SA / agar mixture.

[0093] After manufacturing, the capsules were successfully dried in a fluidized bed dryer set to an air inlet temperature (i.e., a temperature lower than the melting point of the oleogel) of 35°C in the presence of 2% by weight of aluminum silicate (used as an anticoagulant) until a fluid powder was obtained. Survival rate analysis of the extracted probiotics, combined with CFU counting, revealed that approximately 90% of the probiotics survived the drying process.

[0094] Example 7: Capsules were prepared in the same manner as in Example 3, but with different core and shell solutions. The core composition contained 2% by weight of probiotics (lyophilized Lactobacillus rhamnosus) suspended in a 5% by weight mixture of carnauba wax in safflower oil instead of LAA in a carnauba wax / sunflower oil mixture, and the shell contained 1.5% by weight of SA instead of SA / agar mixture (shown as "PB Beads 1" in Figure 6).

[0095] In this example, the wax / oil mixture was first heated to 90-100°C to form a clear, homogeneous liquid, then cooled to 45°C, after which the probiotic-containing powder was added and mixed. Furthermore, capsules having the same composition as PB Beads 1 were prepared using a different core liquid preparation method that resulted in a more heterogeneous wax distribution throughout the oleogel core (shown as "PB Beads 2" in Figure 6).

[0096] Specifically, in the case of PB Beads 2, a 10% carnauba wax / safflower oil mixture without probiotics was heated to 90-100°C, then cooled to 50°C, and then a probiotic-containing oil at room temperature (i.e., approximately 20-25°C) was added in a 1:1 ratio to reach a final carnauba concentration of 5%. Blending a warmer wax / oil mixture with a colder probiotic-containing oil would presumably result in substantial wax crystallization and oleogel formation before the encapsulation process using microfluidic technology in the air, ultimately leading to reduced uniformity and protection of the oleogel network surrounding the probiotics.

[0097] Furthermore, another batch of probiotic-containing capsules was prepared in a similar manner to PB Beads 1, but the core composition subsequently contained probiotics in a mixture of 4% by weight of candelilla wax in safflower oil (shown as "PB Beads 3" in Figure 6).

[0098] Analysis of probiotic survival rates after stability testing of capsules in an aqueous base at 25°C revealed that the probiotic survival rate in PB Bead 1 was significantly higher than that in PB Bead 2 and PB Bead 3. This indicates that both formulation and encapsulation process parameters play a crucial role in the final degree of protection and prevention against probiotic mortality, as well as in extending shelf life, particularly in applications under wet or humid conditions.

[0099] Example 8: Microcapsules were prepared in the same manner as in Example 3, but using different core and shell liquids. Instead, the core composition contained 10% by weight of LAA and 5% by weight of carnauba wax in high-oleic sunflower oil, and the shell composition contained (gelling) SA / agar / CMC. The capsules were supplied as a 50-60% slurry in an aqueous medium in a wide-mouthed, high-density polyethylene container, followed by transport testing in accordance with ASTM D4169-16, which passed, and then stability testing.

[0100] For stability testing, capsules were removed from their containers, separated from aqueous transport media by sieving, blended in various aqueous liquids and gels, and subjected to different storage conditions at 4, 21, 30, 40, and 60±2°C for a minimum of 3 months. LAA was extracted from the capsules using sonication in ethanol, and the antioxidant activity of the extracted LAA was measured using a 2,2-diphenyl-1-picrylhydrazyl assay combined with spectrophotometric analysis.

[0101] Encapsulated active LAAs exhibit significantly higher antioxidant activity, a more slowed decline in antioxidant activity, and a longer antioxidant half-life compared to unencapsulated active LAAs (i.e., controls) (Figure 7).

[0102] Although the present invention has been described in more detail above based on only a limited number of examples and embodiments, it should be clear that the invention is by no means limited thereto. Rather, many modifications and embodiments are still possible within the scope of the invention for those ordinary people skilled in the art.

[0103] As an example, the methods, formulations, and preservatives according to the present invention may be used in embodiments in which the active compound comprises at least one vitamin, particularly a vitamin selected from the group comprising thiamine, riboflavin, nicotinic acid, pantothenic acid, pyridoxine, biotin, folic acid, cyanocobalamin, lipoic acid, ascorbic acid, lecithin, glycyrrhizic acid, retinol, retinyl palmitate, tocopherol, tocopherol acetate, salicylic acid, benzoyl peroxide, azelaic acid and / or derivatives, and more specifically, ascorbic acid and / or derivatives.

[0104] Furthermore, the methods, formulations, and preservatives according to the present invention may be used in embodiments in which the active compound comprises at least one antioxidant, particularly an antioxidant selected from the group comprising polyphenols, thiol compounds, sulfites, and their derivatives.

[0105] The active compound can be used, for example, as a dietary supplement or for pharmaceutical treatment, in which case it is likely to be administered orally. The shell layer can be formulated to withstand the acidic environment of the human stomach so that it is digested in the downstream part of the user's digestive tract to release the contents. In particular, the shell layer may contain digestible or fermentable polymers, and more specifically, the shell layer may contain pectin compounds. Specifically, probiotics and prebiotics can be administered particularly effectively in this manner. In particular, the shell layer may carry a coating, preferably an edible coating, in particular a hydrophobic coating containing nanoparticles or waxes such as carnauba wax.

Claims

1. A method for preserving an active compound, comprising: a powder containing the active compound; the powder being dispersed in a liquid hydrophobic material that is at least partially gellable or crystallable to form a suspension or dispersion containing the powder; the suspension or dispersion being formed into microbodies; the microbodies being encapsulated by a polymer shell to form microbodies containing the suspension or dispersion, each containing one or more cores of the suspension or dispersion; and the microbodies containing the suspension or dispersion being at least partially solidified, particularly gelled and / or crystallized, to form microbodies containing the active compound within a hydrophobic network that is at least substantially solidified.

2. The method according to claim 1, characterized in that the liquid hydrophobic material is treated in a liquid state and at least partially solidifies or solidifies at a temperature lower than its solidification temperature.

3. The method according to claim 2, characterized in that the liquid hydrophobic material is cooled to a temperature lower than its solidification temperature at a cooling rate faster than 0.1 K / min, particularly faster than 1 K / min, more specifically faster than 10 K / min, and more specifically faster than 100 K / min.

4. The method according to claim 2 or 3, characterized in that the liquid hydrophobic material is solidified by combining a phase having a temperature lower than the solidification temperature of the liquid hydrophobic material, particularly a temperature lower than room temperature, and more specifically a temperature of less than 10°C, in particular a liquid phase and microbodies.

5. The method according to claim 4, characterized in that the phase includes a liquid phase containing a crosslinking compound that crosslinks the shell polymer.

6. The method according to claim 5, characterized in that the liquid phase has a temperature that induces at least one thermal or physical crosslinking of the shell polymer.

7. The method according to any one of the claims, characterized in that the one or more microbodies contain the hydrophobic compound by immersing the one or more microbodies in a solution, particularly a concentrated solution, of the hydrophobic compound, thereby allowing the hydrophobic compound to diffuse through the shell into the one or more cores of the one or more microbodies.

8. The method according to any one of the claims, characterized in that the microbodies contain the hydrophobic compound, comprising: providing one or more microbodies having one or more cores in a molten state; then immersing the one or more microbodies in a solution, particularly a concentrate, of a hydrophobic compound, thereby enabling the hydrophobic compound to diffuse into the one or more cores of the one or more microbodies in a molten state; and subsequently solidifying the one or more cores at least substantially.

9. The method according to any one of the claims, characterized in that the microbody is dried by a drying method selected from the group including evaporation, blowing in a drying gas, vacuum drying, fluidized bed drying, freeze-drying, microwave drying, and chemical drying.

10. A preservative for an active compound, comprising one or more preservative microbodies, each having at least one core surrounded by a shell formed by a polymer network, wherein the core comprises at least a substantially solidified, particularly gelled, gellable or crystallable liquid hydrophobic material, particularly an oleogel, and a solid powder, the powder dispersed throughout the core, and the powder comprising the active compound.

11. A formulation containing an active compound preserved by the preservative described in claim 10.

12. The formulation according to claim 11, which is used in, or applied to, cosmetics, personal care or home care products, dermatological products, food or nutritional products, pesticide products, fragrance products, health or wellness products, pharmaceuticals, (bio)medical products, household goods, energy storage products, coating products, or adhesive products.

13. A method, preservative, or formulation according to any one of the claims, characterized in that the shell comprises a calcium arginate network, the calcium arginate network is weakened or completely removed, more specifically by introducing a chelating agent such as citrate or ethylenediaminetetraacetic acid (EDTA), before or during final application, particularly by scavenging calcium ions and at least partially destroying the calcium arginate network of the shell.

14. The method, preservative or formulation according to any one of the claims, characterized in that the shell is designed to disintegrate or break down under induced chemical or mechanical conditions, thereby releasing the active compound, including the powder, from the microbody.

15. The shell is characterized by comprising a polymer network, particularly an interpenetrating network, a double network, and / or a complex of two or more intermolecular or intramolecular crosslinked polymers, more specifically, the polymer network comprising a hydrophilic polymer network, particularly agar, arginate, chitosan, dextran, poly(ethylene glycol), collagen, gelatin, hyaluronic acid, carrageenan, particularly lambda, kappa and lota carrageenan, fibroin, fibronectin, poly-l-lysine (PLL), cellulose, graphene, poly(ethylene glycol) A preservative or formulation according to any one of the claims, characterized by comprising one or more polymer electrolytes or polysaccharides selected from lenymine (PEI), poly(amidoamine) (PAA), dextran sulfate, silk, silk fibroin, pectin, locust bean gum, gellan gum, guar gum, tragacanth gum, xanthan gum, acacia gum, karaya gum, starch, and sodium carboxymethylcellulose (S-CMC), wherein all of these are naturally derived materials and / or synthetic materials including recombinant proteins and / or derivatives thereof.

16. The method, preservative or formulation according to any one of the claims, characterized in that the shell comprises a biocompatible, biodegradable and / or bioabsorbable polymer network, particularly a polymer network comprising a methyl-methacrylate derivative, a caprolactone derivative, a lactic acid derivative, a glycolic acid derivative, and / or a copolymer of lactic acid and glycolic acid, more specifically, the polymer network comprising poly(lactic acid-co-glycolic acid), poly(caprolactone), and / or poly(methyl methacrylate).

17. The method, preservative or formulation according to any one of the claims, characterized in that the polymer network comprises a crosslinked or interpenetrating arginate network, particularly a calcium crosslinked arginate network.

18. The method, preservative or formulation according to claim 17, characterized in that the network is enhanced by incorporating nanoparticles, microparticles and / or polymer electrolytes.

19. The method, preservative or formulation according to claim 18, characterized in that the polymer shell comprises an arginate network, particularly a sodium, calcium and / or shellac-reinforced arginate network.

20. The liquid hydrophobic material is at least one oil, particularly, - Vegetable oils, such as sunflower oil, corn oil, linseed oil, canola oil, castor oil, palm oil, coconut oil, avocado oil, sweet almond oil, calophyllum oil, sesame oil, olive oil, jojoba oil, soybean oil, cottonseed oil, rapeseed oil, peanut oil, linseed oil, borage oil, safflower oil, macroalgae oil and seaweed oil, - Essential oils, ether oils, macerated oils, triglycerides, - Animal oils, such as animal fat, lanolin and marine oils, such as fish oil, - Synthetic oils, and - Neutral oils such as medium-chain triglyceride oils and mixtures or derivatives thereof, more specifically non-toxic and easy-to-use oils, especially sunflower oil or safflower oil. The method, preservative or formulation according to any one of the claims, characterized by comprising one or more oils from the group including the above.

21. The method, preservative, or formulation according to any one of the claims, characterized in that the hydrophobic material is an oleogel containing oil, more specifically sunflower oil, which retains more than 90% of the oil, particularly more than 95%, of the oil at 40°C for at least four weeks.

22. The method, preservative or formulation according to any one of the claims, characterized in that the liquid hydrophobic material is provided in liquid form and is gelled or solidified to form the microbodies, comprising one or more fatty acids and / or waxes from the group comprising fatty acid esters having short-chain alcohols, particularly carnauba wax, including: paraffin wax, rice bran wax, sunflower wax, carnauba wax, candelilla wax, beeswax, microcrystalline wax, coconut wax, ozocerite wax, beta-sitosterol, gamma-oryzanol, stearic acid, palmitic acid, behenic acid, myristic acid, lauric acid, capric acid, and fatty acid derivatives, such as isopropyl myristate, isopropyl palmitate and isopropyl stearate, and dibutyl adipate.

23. The method, preservative, or formulation according to any one of the claims, characterized in that the liquid hydrophobic material comprises one or more gelling agents selected from the group consisting of hydrophilic gelling agents, particularly polysaccharides, (modified) starch, protein, natural gum, hydrocolloid, steroid, hydrophilic phytosterol derivative, or phospholipids, particularly cellulose, maltodextrin, dextran, hyaluronic acid, gelatin, whey protein, acacia gum, tragacanth gum, xanthan gum, carrageenan, agar, lecithin, propylene glycol, silica (nanoparticles), and more specifically, ethylcellulose.

24. The method according to any one of the claims, a preservative or a formulation, characterized in that the liquid hydrophobic material has a solidification temperature of 0°C to 100°C, particularly 4°C to 90°C, particularly 4°C to 40°C, particularly 20°C to 40°C, particularly 20°C to 90°C, particularly 40°C to 90°C, particularly 40°C to 50°C, particularly 50°C to 60°C, particularly 60°C to 70°C, particularly 80°C to 90°C, preferably a temperature above room temperature.

25. The method, preservative, or formulation according to any one of the claims, characterized in that the liquid hydrophobic material has a solidification offset temperature of less than about 60°C.

26. The method, preservative, or formulation according to any one of the claims, characterized in that the liquid hydrophobic material comprises an emulsifier or plasticizer, such as fatty acids, glycolipids, monoglycerides, diglycerides, triglycerides, or phospholipids, or mixtures thereof, particularly soy lecithin or polyglycerol polyricinoleate (PGPR).

27. The method, preservative, or formulation according to any one of the claims, characterized in that the liquid hydrophobic material contains an oil-soluble antioxidant, such as tocopherol (known as vitamin E), particularly alpha-tocopherol, particularly 0.01 to 10% by weight of alpha-tocopherol in the oleogel, particularly 0.1 to 1% of alpha-tocopherol in the oleogel.

28. The method, preservative or formulation according to any one of the claims, characterized in that the powder is provided as a dry, substantially water-free powder.

29. The method, preservative or formulation according to any one of the claims, wherein the powder comprises one or more antioxidants and / or nutrients, particularly catalase, polyphenols, curcumin, quercetin, catechin, lignan, resveratrol, citric acid and L-ascorbic acid, and in particular, the powder comprises L-ascorbic acid.

30. The method, preservative or formulation according to any one of the claims, characterized in that the active compound is a wettable powder, particularly hyaluronic acid, arginate, gelatin or collagen.

31. The method, preservative, or formulation according to any one of the claims, characterized in that the powder comprises a hydrophilic polymer having a molecular weight of more than 10 kDa, particularly more than 100 kDa, and particularly more than 1000 kDa, a polysaccharide, particularly hyaluronic acid.

32. The method, preservative or formulation according to any one of the claims, characterized in that the powder comprises a hygroscopic compound, particularly a natural compound, particularly a natural compound from the group consisting of hydrophilic polymers, polysaccharides, proteins, nucleic acids, and water-soluble salts.

33. The method, preservative, or formulation according to any one of the claims, characterized in that the powder contains one from the group consisting of hygroscopic salts, particularly salts of quaternary ammonium cations, more specifically choline salts, particularly choline chloride, choline tartrate, choline borate, choline dihydrogen citrate, choline bicarbonate, and choline carbamate, and even more specifically choline chloride.

34. The method according to any one of the claims, a preservative or a formulation, characterized in that the powder comprises a biological compound, particularly an organism, a protein, an enzyme, a peptide, a nucleotide, or a mixture thereof.

35. The method, preservative or formulation according to any one of the claims, characterized in that the powder contains viable compounds, particularly living cells, more specifically bacteria or a microbiome.

36. The aforementioned powder contains Bacteroides, Bifidobacterium, Fusobacterium, Bacillus, Lactobacillus, Saccharomyces, Streptococcus, and Enterococcus porphyromonas. One or more bacteria from the group consisting of Porphyromonas, Prevotella, Actinomyces, Propionibacterium, and Clostridia, particularly Bifidobacterium bifidum, Bifidobacterium lactis, Bifidobacterium adolescentis, and Bifidobacterium breve. Bifidobacterium infantis, Bifidobacterium longum, Lactobacillus acidophilus, Lactobacillus rhamnosus, Saccharomyces boulardii, Lactobacillus plantarum, Streptococcus thermophilus thermophilus, Lactobacillus casei, Lactobacillus paracasei, Lactobacillus reuteri, Lactobacillus fermentum, Bacillus coagulans, Bacillus subtilisThe method, preservative, or formulation according to any one of the claims, characterized by comprising one or more bacteria from the group consisting of *subtilis* and *Enterococcus faecium*.

37. The method according to any one of the claims, a preservative or a formulation, characterized in that the powder contains one or more prebiotics, particularly one or more prebiotics from the group consisting of oligosaccharides, fructans, galactans, starches, pectins and beta-glucans.

38. The aforementioned powder is a catalyst, in particular, - In particular, compounds that catalyze amino crosslinking, including p-TSA (para-toluenesulfonic acid), DNNDSA (dinonylnaphthalene disulfonic acid), DDBSA (dodecylbenzenesulfonic acid), DNNSA (dinonylnaphthalene monosulfonic acid), phosphoric acid, and carboxylic acids, or - Compounds that catalyze urethane crosslinking, particularly DBTL (dibutyltin laurate), DOTL (dioctyl laurate), DBTO (dibutyltin oxide), bismuth-based catalysts, zirconium-based catalysts, and amine-based catalysts. The method according to any one of the claims, a preservative, or a formulation, characterized by comprising one or more compounds from the group consisting of the above.

39. The method, preservative or formulation according to any one of the claims, characterized in that the liquid hydrophobic material contains oil, more specifically, oil having an oleic acid content of more than 10%, more specifically more than 25%, more specifically more than 50%, and more specifically more than 70%, and even more specifically, oleogel containing high-oleic sunflower oil characterized by an oleic acid content of more than 70%.

40. The method, preservative, or formulation according to claim 39, characterized in that the oleogel holds a considerable amount of the oil, and more specifically, the oleogel has the ability to bind or hold more than 90% of the oil in the oleogel, particularly more than 95% of the oil in the oleogel, for at least four weeks at room temperature or above, particularly 40°C.

41. The method, preservative, or formulation according to claim 39 or 40, characterized in that the oleogel contains at least 1% by weight (gelling agent relative to the weight percentage of the oleogel), particularly at least 2% by weight, particularly at least 3% by weight, particularly at least 4% by weight, particularly at least 5% by weight, particularly 1% to 10% by weight, and particularly 4% to 6% by weight of an oil gelling agent.

42. The method according to claim 39, 40, or 41, characterized in that the water activity (aw) of the oleogel is less than 0.7, particularly less than 0.6, particularly less than 0.5, particularly less than 0.4, particularly less than 0.3, particularly less than 0.2, and particularly less than 0.

1.

43. The method, preservative, or formulation according to any one of the claims, characterized in that the microbody comprises microdroplets or nanodroplets having a size ranging from submicrons to millimeters.

44. The method, preservative, or formulation according to any one of the claims, characterized in that the shell encloses a volume ranging from about 1 femtoliter to about 1 to several milliliters.

45. The method, preservative, or formulation according to any one of the claims, characterized in that the microbody has a diameter of approximately 0.5 microns to 1 centimeter, particularly 5 microns to 5 millimeters, particularly 100 to 500 microns, and more specifically 150 to 350 microns, 500 to 5000 microns, 1 to 5 millimeters, or 2 to 4 millimeters.

46. The method, preservative or formulation according to any one of the claims, characterized in that the microbody is substantially spherical and has a sphericity of greater than 0.8, particularly greater than 0.9, and more specifically greater than 0.

95.

47. The method, preservative, or formulation according to any one of the claims, characterized in that the microbodies have substantially the same size within a size distribution (degree of dispersion) exhibiting a relative size distribution characterized by a coefficient of variation of less than 10%, more particularly less than 7.5%, and more specifically less than 5%.

48. The method, preservative or formulation according to any one of the claims, characterized in that the suspension contains the powder at a concentration of more than 0.01% by weight / weight (wt%), particularly more than 1% by weight, particularly more than 10% by weight, particularly 0.01 to 65% by weight, particularly 0.1 to 50% by weight, particularly 0.5 to 5% by weight, particularly 5 to 40% by weight, particularly 5 to 15% by weight, and particularly about 10% by weight.

49. The method, preservative or formulation according to any one of the claims, characterized in that the water content of the suspension is less than 40%, particularly less than 30%, particularly less than 20%, and particularly less than 10%.

50. The method, preservative, or formulation according to any one of the claims, characterized in that the water activity (aw) of the suspension is less than 0.7, particularly less than 0.6, particularly less than 0.5, particularly less than 0.4, particularly less than 0.3, particularly less than 0.2, and particularly less than 0.

1.

51. The method, preservative, or formulation according to any one of the claims, characterized in that the powder comprises a dried, spray-dried, or freeze-dried composition comprising a drying excipient for the active ingredient (hygroscopic), particularly a drying excipient comprising at least one polycarbohydrate, monosaccharide, disaccharide, or polysaccharide compound, more specifically a drying excipient that is a sugar, more specifically a drying excipient selected from the group consisting of dextran, dextrin, maltodextrin, trehalose, lactose, glucose, dextrose, sucrose, fructose, maltose, isomaltose, sorbitol, mannitol, lactitol, xylitol, and / or erythritol.

52. The method, preservative or formulation according to any one of the claims, characterized in that the powder comprises one or more susceptible bacteria selected from the group consisting of anaerobic bacteria, non-spore-forming bacteria and other bacteria sensitive to moisture, acid, heat and / or oxygen.

53. The powder contains one or a so-called "next-generation probiotic," more specifically, the powder contains Akkermansia muciniphylla, Faecalibacterium prausnitzii, Bacteroides thetaiotaomicron, Bacteroides fragilis, Roseburia sp., Prevotella sp., Aristipes sp., Christensenella minuta The method according to any one of the claims, a preservative or formulation, characterized by comprising one or more next-generation probiotics from the group consisting of *Blautia minuta*, *Blautia sp.*, *Eubacterium hallii*, and *Methanobrevibacter smithii*.

54. The method, preservative or formulation according to any one of the claims, characterized in that the active ingredient has a functional property that is masked by the at least one core in the microbody.

55. The method, preservative, or formulation according to claim 54, characterized in that the active ingredient is a fragrance, a scent, or a mixture of compounds that produce an odor.

56. The method, preservative, or formulation according to claim 54, characterized in that the active ingredient is a flavor, or comprises a mixture of a flavor compound and an unpleasant-tasting compound.

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