Foam for delivering functional components

Abstract

The present disclosure provides a delivery system for functional ingredients, such as drugs, nutritional supplements, botanicals, and vitamins. The delivery system includes an ingestible matrix, and the functional ingredient is substantially uniformly and completely dispersed within the ingestible matrix. The matrix includes a foam obtained by physical shearing of egg white, achieving an increased available dosage and improved release characteristics of the functional ingredient on skin and mucosal surfaces for health care purposes. The disclosure also provides methods for preparing and using the delivery system.

Description

Technical Field

[0001] The present disclosure relates to the field of health or functional components including pharmaceuticals and nutrients, and systems for delivering such health or functional components.

Background Art

[0002] Functional components including pharmaceuticals such as antibiotics, antiseptics, topical disinfectants, etc., designed to treat or prevent infectious diseases, and nutritionals including vitamins, amino acids and essential fatty acids, designed to enhance human and animal health and well-being, are gaining popularity, as is evident from the very large growth of the industries involved in their manufacture, production, and distribution. Among the various classes of functional components, many are water-soluble, some are soluble only in oil, while some are amphiphilic, showing partial solubility in both oil and water, like surfactants. The solubility of any functional component has a great influence on the appropriate delivery method of the functional component to the human or animal body, especially in the case of oral application where the functional component is intended to affect reactions on or within the gastrointestinal tract, and in the case of topical or mucosal application where the functional component is intended to affect reactions on or within the skin or mucosa, and thus on structures originating from such surfaces (e.g., hair, nails and teeth). Formulations of poorly soluble functional components usually contain excipients designed to promote solubility, absorption and / or residence time at the target surface. The available dosage of any functional component in such a formulation is also limited by the amount of formulation applicable to the target surface, and by the transfer or release of the functional component from the formulation onto or into the target surface.

[0003] Several different delivery systems have been developed in an attempt to improve the delivery of various supplements or functional ingredients. For example, several capsules have been developed that encapsulate or hold functional ingredients within various glassy, sintered, or chewy confectionery-type matrices. Generally, confectionery serves as a solid continuous matrix for active ingredients or active supplements. The active ingredients are delivered according to the dissolution rate of the confectionery matrix, giving a firm taste in the mouth. Crushing the confectionery is a solution for the consumer to speed up the release of the active ingredient, but this solution may cause dental problems and / or the release rate of the active ingredient incorporated in the confectionery may no longer be optimal, so it may not be desirable. Depending on the method of manufacturing the confectionery matrix, the active ingredients may be subject to degradation or damage due to heat and / or mechanical stress during the manufacturing process. Often, the high degradation rate due to strong manufacturing conditions is compensated for by over-dosing the active ingredients in the confectionery matrix, which is an expensive method that results in a significant waste of many active ingredients. The "firm" taste that a pressed tablet or glassy matrix can give in the mouth may also not be very attractive from the perspective of active ingredient delivery, especially if the taste is not to the consumer's liking. Therefore, it is desirable to provide a system for efficiently delivering functional ingredients having improved solubility and release characteristics, particularly for amphiphilic and lipophilic functional ingredients.

Summary of the Invention

[0004] According to an aspect of the present disclosure, there is provided a delivery system for one or more functional ingredients, the delivery system representing a matrix of a foamed foam, the one or more functional ingredients being substantially uniformly dispersed, and the matrix comprising i) an egg white component containing a protein concentration of 1 to 50%; ii) one or more heat-resistant and / or heat-sensitive gelling agents; iii) a pH adjuster; iv) one or more plasticizers and / or wetting agents; and v) in one or more aqueous media comprising and being solid at room temperature, provides the delivery system. In another aspect of the present disclosure, there is provided the use of a delivery system for oral administration of one or more functional components to an animal in need thereof.

[0005] In embodiments, the present disclosure provides a method for improving the oral health of a companion animal. In certain embodiments, the present disclosure provides a method for maintaining or improving the oral health of a subject in need thereof, the method comprising administering to the subject an available dosage of an oral antimicrobial composition, the oral antimicrobial composition comprising: (a) one or more saturated or unsaturated free fatty acids or pharmaceutically acceptable salts thereof; and (b) one or more delipidised membrane lipids as emulsifiers for the free fatty acids or pharmaceutically acceptable salts thereof. In embodiments, the present disclosure provides a method for oral delivery of a health-related composition comprising one or more health components, the health-related composition being used for oral health, joint health and mobility, cardiovascular health, bone health, skin health, gastrointestinal health, anti-stress / relaxation or other behavioral states, anti-parasiticides such as anti-flea and anti-tick, or vaccines for companion animals. Additional variations and advantages of the present disclosure will become apparent from the detailed description of the present disclosure in conjunction with the accompanying examples.

DETAILED DESCRIPTION OF THE INVENTION

[0006] In the present disclosure, and particularly in the claims, it should be noted that terms such as "comprises", "comprised", "comprising", etc. can mean "includes", "included", "including", etc., and terms such as "consisting essentially of" and "consists essentially of" allow elements not specified, except for elements found in the prior art or elements that affect the basic or novel characteristics of the present disclosure. Unless otherwise indicated, technical terms are used according to their conventional usage. Definitions of common terms in molecular biology can be found in Benjamin Lewin, Genes V. 1994 (ISBN 0-19-854287-9) published by Oxford University Press in 1994; Kendrew et al. (editors), The Encyclopedia of Molecular Biology (ISBN 0-632-02182-9) published by Blackwell Science Ltd. in 1994; and Robert A. Meyers (editor), Molecular Biology and Biotechnology: A Comprehensive Desk Reference (ISBN 1-56081-569-8) published by VCH Publishers, Inc. in 1995.

[0007] As used above and throughout the description of the present disclosure, the following terms should be understood to have the following meanings, unless otherwise indicated. The singular terms "a", "an", and "the" include the plural referents unless the context clearly indicates otherwise. Similarly, the word "or" is intended to include "and" unless the context clearly indicates otherwise. The word "or" means any member of a particular list and includes any combination of members of that list. Also, terms such as first, second, etc. can be used in this specification to describe various elements, but it should be understood that these elements should not be limited by such terms. Such terms are only used to distinguish one element from another. For example, without departing from the scope of the present disclosure, the first gesture may be referred to as the second gesture, and similarly, the second gesture may be referred to as the first gesture. All methods and processes described in this specification can be performed in any suitable order unless otherwise indicated herein or clearly contradicted by the context.

[0008] The term "about" as used in this specification means approximately, in the region of, roughly, or around. When the term "about" is used in conjunction with a numerical range, it modifies that range by extending the boundaries above and below the recited numerical values. Generally, the term "about" is used in this specification to vary the numerical values above and below the recited value by a variation of 10%. In one aspect, the term "about" means plus or minus 10% of the numerical value being used. Thus, about 50% means the range of 45% to 55%. Numerical ranges recited by endpoints in this specification include all numbers and fractions subsumed within that range (e.g., 1 to 5 includes 1, 1.5, 2, 2.75, 3, 3.90, 4, and 5). It should be understood that all numbers and their fractions are also presumed to be modified by the term "about".

[0009] The terms "subject", "patient", "user", and "individual" are used interchangeably in this specification to refer to a human or an animal. The terms "animal" and "companion animal" are used herein to include all mammals, birds, and fish. The animals used herein can be selected from the group consisting of equine animals (e.g., horses), canid animals (e.g., dogs, wolves, foxes, coyotes, jackals), feline animals (e.g., lions, tigers, house cats, wild cats, other large cats, and other feline animals including cheetahs and lynxes), bovine animals (e.g., cows), swine (e.g., pigs), ovine animals (e.g., sheep, goats, llamas, bison), birds (e.g., chickens, ducks, geese, turkeys, quails, pheasants, parrots, finches, eagles, crows, ostriches, emus, and cassowaries), primates (e.g., prosimians, tarsiers, monkeys, gibbons, apes), humans, and fish.

[0010] Any examples provided herein or all examples, or the use of exemplary language (e.g., "such as") are merely intended to make the disclosure clearer and do not limit the scope of the disclosure unless otherwise indicated. No language in this specification should be construed as indicating an essential element for the practice of the disclosure unless explicitly stated. The term "carrier" refers to a diluent, adjuvant, excipient, or vehicle administered together with an active / functional ingredient. Such pharmaceutical carriers may be sterile liquids such as water and oils, including sterile liquids of animal, plant, or synthetic origin (e.g., peanut oil, soybean oil, palm oil, mineral oil, sesame oil, etc.). As carriers, particularly for injectables, water or aqueous solutions, physiological saline, aqueous dextrose, and glycerin solutions are preferred. Alternatively, the carrier may be a carrier for solid dosage forms and includes, but is not limited to, one or more binders (for compressed pills), lubricants or lubricating agents, encapsulating agents, flavoring agents, and coloring agents. Suitable pharmaceutical carriers are described in "Remington's Pharmaceutical Sciences" by E. W. Martin (Mack Publishing Co., Easton, Pa.); Gennaro, A. R., Remington: The Science and Practice of Pharmacy, (Lippincott, Williams and Wilkins); Pharmaceutical Dosage Forms, edited by Liberman et al., Marcel Decker, New York, N.Y.; and Handbook of Pharmaceutical Excipient, edited by Kibbe et al., American Pharmaceutical Association, Washington.

[0011] As used herein, the terms "effective amount" or "effective dosage" refer to an amount of a health component that is known in the art to confer a health benefit. The effective amount in a composition, when used as disclosed herein, is an amount that is high enough to provide the desired effect or benefit relative to a reasonable benefit / risk ratio, but is also low enough to avoid adverse effects such as toxicity, irritation, or allergic reactions. Such effective amounts can be readily determined by one of ordinary skill in the art and will vary depending on factors such as the specific health component used, the particular condition being treated, the age and general health of the subject, the duration of treatment, the nature of any combination therapies (if any), the specific dosage form used, the carrier used, the solubility of the dosage form, and the specific dosing schedule.

[0012] The terms "health component" and "functional component" are used interchangeably herein and refer to components or ingredients that enhance health and well-being, prevent disease, or improve well-being, including pharmaceuticals such as antibiotics, disinfectants, topical antiseptics, etc. designed to treat or prevent infections, antioxidants, phytochemicals, hormones, vitamins such as vitamin A, B1, B2, B6, B12, C, D, E, K, pantothenate, folic acid, provitamins, minerals such as calcium salts, selenium salts, magnesium salts, available iron, and iron salts, microorganisms such as bacteria (e.g., live lactic acid bacteria), fungi, and yeast, prebiotics, probiotics, trace elements, essential and / or highly unsaturated fatty acids such as omega-3 fatty acids and medium-chain triglycerides, nutritional supplements, enzymes such as amylase, protease, lipase, pectinase, cellulase, hemicellulase, pentosanase, xylanase, and phytase, pigments, oligopeptides, dipeptides, and amino acids, and mixtures thereof.

[0013] As used herein, the term "prebiotics" refers to "non-digestible food ingredients that provide beneficial effects to the host by selectively stimulating the growth and / or activity of one or a limited number of bacteria in the colon that can improve the health of the host", for example, those in Gibson, G. R. & Roberfroid, M. B., Dietary Modulation of the Human Colonic Microbiota-Introducing the Concept of Probiotics, J. Nutr. 125:1401-1412 (1995). Such prebiotics may be natural products, synthetic products, or those developed by genetic manipulation of organisms and / or plants, and their new sources may be those currently known or those developed later. Prebiotics useful in the present disclosure may be oligosaccharides, polysaccharides, and other prebiotics including fructose, xylose, soya, galactose, glucose, and mannose, for example, those in Ramirez-Farias et al., Br J Nutr (2008) 4:1-10; Pool-Zobel and Sauer, J Nutr (2007), 137:2580 S-2584S. More specifically, prebiotics useful in the present disclosure may be lactulose, lactosucrose, raffinose, glucooligosaccharides, inulin, polydextrose, polydextrose powder, fructooligosaccharides, isomaltooligosaccharides, soy oligosaccharides, lactosucrose, xylooligosaccharides, chito-oligosaccharides, mannan oligosaccharides or manno-oligosaccharides (MOS), arabino-oligosaccharides, sialyl oligosaccharides, fucooligosaccharides, galactooligosaccharides, and gentiobiooligosaccharides. Furthermore, prebiotics useful in the present disclosure include molecules such as β-methyl-d-galactoside and N-acetyl-d-mannosamine, for example, those in Slomka et al., J Clin Periodontol. (2017), 44(4):344-352.In one embodiment, the daily dose of the prebiotics is from about 0.00001 g to about 1 g, more preferably from about 0.0001 g to about 0.5 g, and even more preferably from about 0.0005 g to about 0.1 g.

[0014] As used herein, the term “probiotics” refers to live microorganisms, dead microorganisms, and inactivated microorganisms that, when administered in appropriate dosages, confer a beneficial effect on the health or well-being of a host. Examples of such probiotics can include substantially pure bacteria (i.e., single isolates) or mixtures of desired bacteria. Health benefits may include those related to cardiovascular health, bone health, gastrointestinal health, oral health, skin or dermal health, anti-stress or behavioral health, and immune health. For the purposes of the present disclosure, “probiotics” further intends to include, unless otherwise indicated, active metabolites produced by the microorganisms of the present disclosure. Such cell metabolites can be obtained by using lysates or fermentation supernatants of probiotic bacteria. Metabolites can include organic and inorganic molecules, alcohols, aldehydes, amino acids, carbohydrates and their components, peptides, proteins and their components, extracellular enzymes, cell wall-bound enzymes, membrane-bound enzymes or intracellular enzymes, electron transfer molecules and their components, or other cell wall, membrane or cytoplasmic components and molecules, hormones or hormone-like substances, lipids, oils, fats or fatty acids and their components, organic acids, nucleic acids or ribonucleic acids and their components, carbon compounds, nitrogen compounds, phosphate compounds, pigments, and vitamins, as well as mixtures of any of the foregoing components and molecules, such as those in Fernandez-Gutierrez et al., (2017) Scientific Reports | 7: 11100 | DOI:10.1038 / s41598-017-11446-z, and such as those in MacKenzie et al., Microbiology (2010), 156, 3368-3378. For the purposes of the present disclosure, “probiotics” further intends to include inactivated or dead probiotic bacteria and yeasts, such as specific microorganisms, or other prokaryotic or eukaryotic cells, and those used for coaggregating these components.

[0015] Examples of microorganisms generally recognized as probiotics include Acetobacterium, Acetitomaculum, Bacillus, Bacteroides, Bergeyella, Bifidobacterium, Blautia, Capnocytophaga, Clostridium, Corynebacterium, Enterococcus, Eubacterium, Holophaga, Lactobacillus, Lautropia, Leuconostoc, Moraxella, Moorella, Neisseria, Pasteurellaceae, Prevotella, Ruminococcus, Saccharomyces, Sporomusa, Staphylococcus, Stenotrophononas, Streptococcus, Treponema, Weissella, Wolinella, and Xenophilus, as well as mixtures thereof.More specifically, it is Bifidobacterium animalis, Bifidobacterium lactis, Bifidobacterium longum, Lactobacillus brevis, Lactobacillus helveticus, Lactobacillus johnsonii, Lactobacillus paracasei, Lactobacillus plantarum, Lactobacillus reuteri, Lactobacillus rhamnosus, Lactococcus cremoris or Lactococcus lactis, Saccharomyces cerevisiae or Saccharomyces boulardii, Streptococcus salivarius, Streptococcus thermophilus.

[0016] Enzymes and proteins may also be used as health components, for example, amyloglucosidase, glucose oxidase or glucosidase, lactoperoxidase, mutanase, dextranase, lipase, laccase, peptidase or proteinase, xylanase, other polysaccharide-degrading enzymes, and other hydrolases; proteins, for example, colostrum (lactoferrin, secretory IgA), bacteriocin, lytic phage or their components, quorum sensing proteins or other inhibitors in target bacteria and other microorganisms. Lipids and their derivatives that can be administered orally to companion animals include, for example, polyunsaturated fatty acids or omega-3 fatty acids, monounsaturated fatty acids such as 1-tetradecanol complexes (e.g., Hasturk et al., 2007, J Periodontology, Vol 78:924-932), and derivatives of fatty acids described in WO2011 / 061237 and the like. The entire content of such publications and / or patent applications is hereby incorporated by reference and relied upon in its entirety. As used herein, the term "pharmaceutically acceptable" or "veterinarily acceptable" refers to molecular entities and compositions that, when administered to an animal, generally do not produce adverse effects, allergic reactions or other harmful reactions. It will also be understood that for animal administration, the formulation should meet the sterility, pyrogenicity, general safety, and purity standards required by the FDA, USDA, or the European Medicines Agency.

[0017] The terms "palatant", "palatability enhancer", or "flavoring agents, flavoring, flavorants" mean any material or substance that enhances the palatability of a food composition for animals. A palatant or palatability enhancer may be a single material or a mixture of materials, and may be natural (raw or processed), synthetic, or partly natural and partly synthetic. The palatant can be added to the composition as an additive containing the palatant or as an additive containing one or more other functional or non-functional materials together with the palatant. The palatability enhancer can be produced wholly or partly from meat or poultry broth concentrate or spray-dried powder, protein hydrolysate, yeast and / or yeast extract, liver, spices, herbs, sweeteners, or any combination of such ingredients. As used herein, the terms "treating", "treatment", or "to treat" refer to reversing, reducing, or suppressing the progression of a disease, disorder, or condition; or reducing the likelihood or incidence of the occurrence of a disease or condition in a subject as compared to an untreated control group or as compared to the same subject prior to treatment; or delaying or preventing the symptoms associated with the disease, disorder, or condition. As used herein, "treating" may also refer to preventing the recurrence of a disease, disorder, or condition, or the symptoms associated with such a disease, disorder, or condition.

[0018] Delivery system The delivery system of the present disclosure includes an ingestible matrix, in which one or more functional components are substantially uniformly and completely dispersed, and the solubility and release characteristics of the delivery of any functional component in the ingestible matrix are significantly promoted by using foamed egg white foam as a delivery vehicle. Egg white is a transparent, viscous dispersion of biologically active proteins in an aqueous medium that surrounds the egg yolk of a bird egg. Approximately 10% of the egg white of a chicken egg is a mixed protein containing ovalbumin, ovotransferrin, immunoglobulins, lysozyme, avidin, and the like. Egg white can be separated from the egg yolk by mechanical means and is generally used as a protein source in food and as a binder and thickener in meat products. Egg white can be turned into foam by whisking and beating methods, which usually cause the coiled protein molecules to be forcibly deformed into a linear three-dimensional structure, causing molecular shear that creates a sticky interface with the trapped air bubbles. Among other food uses, egg white foam is used in the production of various confections (such as marshmallows and nougats) that trap air bubbles to create a light, foamy dough by mixing a boiled sugar syrup into the whisked egg white, baking and fixing it, and then cooling it.

[0019] The process of whisking (or beating) egg white generally proceeds through several stages of stiffness, generally referred to as "soft" peaks, "firm" peaks, and "stiff" peaks, after which, if whisking continues, the foam collapses. The volume of whisked egg white is usually about four times larger than the original liquid egg white, and the trapped air bubbles are usually microscopically dispersed along with the occasional large, visible bubbles. Soft-peak and firm-peak foams can be easily mixed with other solutions or solid dispersions in an aqueous medium. This makes soft-peak and firm-peak foams useful for dispersing the trapped air throughout the combined mass. Stiff-peak foams tend to become difficult to disperse and form non-uniform clumps, but can be baked over low heat, forming a crispy honeycomb-like mass, a good example being the meringue of a confection.

[0020] Egg white foams are well-known and commonly used for culinary purposes, but their use in delivering biologically functional components such as nutrients and pharmaceuticals is novel. Also, as disclosed herein, egg white foams facilitate the creation of unique structures that provide great utility with specific classes of functional components designed for therapeutic and nutritional applications. As disclosed herein, a method of using a foamed egg white foam is provided that enables the preparation of a functional component such that the functional component is concentrated at the foam-air interface (i.e., on the inner surface of individual bubbles). An egg white foam having a functional component concentrated on its surface provides a much greater available dosage load compared to conventional topical formulations and can release more rapidly.

[0021] Among various classes of functional components, many are water-soluble, some are soluble only in oil, while some are amphiphilic, showing partial solubility in both oil and water, like surfactants. The solubility of any functional component has a great impact on the appropriate delivery method of the functional component to the human or animal body, particularly in the case of oral application where the functional component is intended to affect reactions in or on the gastrointestinal tract, and in the case of topical or mucosal application where the functional component is intended to affect reactions on or in the skin or mucosa, and thus on structures originating from such surfaces (e.g., hair, nails, and teeth). Generally, functional components including pharmaceuticals and nutrients that are highly soluble in water pose little obstacle to incorporation into any formulation. However, since water-soluble components are freely dispersed throughout the dosage and require the absorption and assimilation of the entire carrier to access the functional component, achieving sufficient release from the formulation is not always easy. Isolating and concentrating freely water-soluble components to enhance delivery can be facilitated using a foamed egg white foam. The water-soluble components are dispersed and immobilized at the foam interface, which has a greatly expanded surface area, increasing the available dosage when the foam itself is dispersed in another carrier.

[0022] Formulations of poorly soluble functional components usually contain excipients designed to promote solubility, absorption and / or residence time at the target surface. The available dosage of any functional component in such a formulation is also limited by the amount of formulation that can be applied to the target surface and the transfer or release of the functional component from the formulation onto or into the target surface. Solubility and release characteristics are important parameters in the delivery of any functional component, and as disclosed herein, both can be significantly enhanced by using foamed egg white foam as a delivery vehicle. Oils and oil-soluble components, as well as many amphipaths, present more difficult problems in formulation. It is well known in the culinary arts that any trace of oil or fat inhibits the foaming of egg white, and similarly, once the egg white has been foamed, the addition of a trace amount of fat, or oil or oil-soluble component causes the foamed foam to collapse. Egg white foam is usually incompatible with any lipophilic (liposoluble) component, which presents a technical challenge in using such foam to enhance the delivery of oil-soluble or amphiphilic functional components.

[0023] The use of emulsification techniques to disperse fine droplets of an oily component, particularly when such droplets are stabilized by an amphiphilic excipient, promotes more flexible uptake and release characteristics from the foamed egg white foam. An emulsion is one in which oil droplets are dispersed in an aqueous medium (oil-in-water type), and an emulsifier is used to prevent the coalescence of the oil droplets. Folan in US Patent Application No. 15 / 384,372 (incorporated herein in its entirety) based on WO2011061237 provides an example of a functional emulsion. In that application, the water-insoluble free fatty acid (oil) is emulsified in a natural-derived membrane lipid, the free fatty acid is preferably caprylic acid, and the emulsifier is preferably defatted lecithin. Surface area is an important parameter that affects the release characteristics and delivery of any functional ingredient. The example of an ointment for the skin serves to illustrate the important properties of surface area. The contact surface of the ointment on the skin is the delivery interface, and the available dose of the functional ingredient is the amount of the functional ingredient at that contact surface. The available dose does not immediately increase upon addition of an additional layer of the ointment because the functional ingredient must first move through the additional layer of the ointment before becoming available at the skin interface. By using egg white foam as the delivery vehicle, the available surface area is significantly increased, and as a result, the release characteristics are also improved.

[0024] In the context of delivering a functional ingredient, it should be recognized that the total surface area of the individual bubbles varies depending on the degree of foaming and the actual protein concentration of the starting solution. For the purposes of this disclosure, it is sufficient to know that the foamed egg white foam, which has approximately quadrupled in volume, exhibits a surface area that is approximately several hundred times larger than the original protein solution or any unfoamed formulation of equivalent volume. As disclosed herein, it is possible to formulate a functional ingredient such that it is concentrated at the foam-air interface (i.e., the inner surface of the individual bubbles) using the foamed egg white foam. The egg white foam having the functional ingredient concentrated on the surface provides a much larger available dose loading and can release more rapidly compared to conventional topical formulations.

[0025] The delivery systems of the present disclosure are suitable for administration to both human and non-human animals. Those skilled in the art will understand that each delivery system can be formulated differently depending on the type of animal to be administered. For example, for administration to animals such as cats or dogs, meat or fish-based seasonings and flavorings can be added. For human administration, the delivery system can be formulated, for example, as a confectionery using fruit-based or other seasonings. The delivery system is particularly suitable for oral administration due to its palatability. In addition, due to its excellent portability, the delivery system can be easily and conveniently administered and ingested by both humans and other animals. The delivery system of the present disclosure can be tailored to specific purposes. Thus, the delivery system can be prepared with a specific combination of functional components to achieve specific physiological effects. Other delivery systems can be prepared, for example, to incorporate certain combinations of drugs or diagnostic agents into the drug delivery system. For example, it can be prepared with a combination of functional components for promoting durability, promoting cardiovascular health, regulating lipids and / or cholesterol, promoting joint health, maintaining or improving bone density, enhancing intracellular antioxidant capacity, or controlling appetite.

[0026] The delivery system of the present disclosure includes one or more functional components substantially uniformly dispersed within a matrix, which generally consists of: 1) egg white with a protein concentration that forms a foamed matrix when foamed; 2) one or more heat-resistant and / or heat-sensitive gelling agents; 3) a pH regulator; 4) one or more plasticizers and / or wetting agents; 5) one or more water sources. By including one or more gelling agents, it facilitates the regulation of the water content and the physical properties of the residual moisture within the matrix. Additives, such as natural or artificial flavorings, colorants, acidulants, buffers, and sweeteners, can be included in the matrix in conventional amounts. The delivery system of the present disclosure can be prepared such that the matrix has a final pH in the range of about 2.5 to about 8.5. In certain embodiments, the matrix has a final pH of about 3.0 to about 8.5. In the art, an acidic pH is known to promote the degradation of certain functional components. For delivery systems prepared to deliver functional components that are sensitive to acidic pH or that react at acidic pH, the final pH of the matrix is thus neutral to weakly basic. Neutral to weakly basic pH means that the final pH is about 6.0 to about 8.5. For functional components that are more stable in acidic form, such as trimethylglycine, or that can react with other components at neutral pH, such as glucosamine hydrochloride, the pH of the matrix of the delivery system can have a final pH below neutral. In certain embodiments of the present disclosure, the delivery system is prepared such that the matrix has a final pH of about 5 and is thus suitable for the delivery of functional components that are stable at acidic pH and / or functional components that do not react at acidic pH.

[0027] As described in the following examples, formulations containing whipped egg white typically include other water-soluble constituents such as gels, polymers, and organic acids, which, when cooked together with the egg white proteins, form a solid scaffold structure of a foam infused with air bubbles. When an oily component or an oil-in-water emulsion is added to the solid matrix, a phase repulsion occurs between the aqueous medium and the oil droplets, moving such droplets to the position of minimum resistance, namely, the water-air interface inside the entrapped bubbles. Due to the greatly enlarged surface area and the concentration of oil droplets on the surface of the foam bubbles, the formulation incorporating emulsified oil will have much more available dosage loading and much faster release characteristics compared to a non-foamed formulation of the same mass. As described below, the texture, physical attributes, morphology, and shape of the matrix can be varied within a predetermined range by using the methods described herein or by varying the ratio of the components by methods well known to those skilled in the art. In addition, the specific selection of the possible components provided below must be safe for animal and / or human ingestion and must meet regulatory standards, such as those of the Codex Alimentarius.

[0028] Egg white foam formulations intended to deliver functionally active emulsions are of great utility in topical skin and mucosal healthcare, for example, when rapid release of the available dosage loading is desirable due to the short transit time on the oral mucosa. Exemplary emulsions include (a) one or more saturated or unsaturated free fatty acids having 4 to 22 carbon atoms or pharmaceutically acceptable salts thereof, and (b) one or more defatted membrane lipids as emulsifiers for the free fatty acids or pharmaceutically acceptable salts thereof. In order to delay digestion in the stomach and enhance the intestinal availability and absorption of functional components contained in the emulsified oil, the same type of modified formulation can be used to protect emulsion droplets by using whipped egg white as a protein coat. Protein digestion in the mammalian stomach is mainly due to the activity of pepsin at low pH. Some of the individual proteins in egg white, particularly ovalbumin and ovomucoid, are particularly resistant to pepsin digestion. The addition of lecithin to the egg white adds resistance to pepsin, and whipping before heating facilitates intact gastric transfer. Upon entering the duodenum, proteolysis by trypsin affects the rapid release of the encapsulated oil-in-water emulsion and its availability for absorption by intestinal cells.

[0029] Emulsions of the type described above are not limited to the use of free fatty acids. Emulsification techniques can be used to deliver oil-soluble components as such or dissolved in other oils such as medium-chain triglycerides (e.g., Miglyol 812N manufactured by IOI Oleo (Hamburg, Germany)). Regardless of the type of oil in the emulsified droplets and any oil-soluble components in the oil, the same oil-water repulsive forces are applied to concentrate the oil droplets at the water-air interface within the foam. Examples of other oil-soluble functional components that benefit from enhanced delivery in emulsions dispersed in whipped egg white foam include, but are not limited to, antibiotics such as mupirocin, antifungal agents such as clotrimazole, disinfectants such as chlorohexidine, anti-inflammatory agents such as ketoprofen, and nutrients such as the fat-soluble vitamins A, D, E, and K. The foamed egg white foam is particularly useful for the uptake and delivery of amphiphilic functional components. Examples of amphiphilic functional components include local anesthetics such as lidocaine, biocides such as benzalkonium chloride, antibacterial agents such as delmopinol, and anti-inflammatory agents such as curcumin. When dispersed in the egg white before and after foaming, the hydrophilic side of the amphiphilic molecule tends to associate with the aqueous proteinaceous matrix, while the lipophilic side (also hydrophobic) naturally aligns at the water-air interface and / or with the lipophilic sides of adjacent molecules, promoting the establishment of micellar and lamellar structures, and all such structures can be used to achieve improved release characteristics.

[0030] In an embodiment, lecithin is used together with the foamed egg white foam. Lecithin is an amphiphilic molecule that can be extracted from plant sources such as soybeans and from egg yolk, which is closely related to but clearly separated from the egg white. As shown herein, lecithin can be combined with the egg white before foaming and, despite its amphiphilicity, has little effect on the foaming properties of the egg white, but significantly promotes the uptake and release of other amphiphilic agents and lipophilic agents (including, but not limited to, delmopinol, curcumin, lidocaine, and benzalkonium chloride) as previously described in detail. In another embodiment, as part of the preparation process, lecithin is used together with the foamed egg white foam to facilitate the in situ construction of free fatty acid emulsions. The foamed egg white is incompatible with oil and will collapse upon the addition of even a trace amount. On the other hand, a method has been developed whereby specific oils such as free fatty acids in the form of water-soluble sodium or potassium salts can be combined with the egg white before foaming without significantly affecting the foaming properties by adding an appropriate amount of an emulsifier such as defatted lecithin to the egg white. After the foam is incorporated into the final formulation, the salt of the free fatty acid can be converted by acidification back to its protonated oil form without affecting the foaming properties.

[0031] Defatted lecithin is amphiphilic, with one side being lipophilic and the opposite side of the same molecule being hydrophilic, thereby exhibiting excellent emulsifying properties. Defatted lecithin can be added to a solution of egg white protein and, when left for a sufficient time to hydrate, it disperses uniformly throughout. In an embodiment, a water-soluble salt of caprylic acid such as sodium caprylate (sodium octanoate) may also be added together with defatted lecithin in an appropriate ratio. A mixture of egg white protein / defatted lecithin / sodium caprylate may be whipped. Due to the added components, the texture of the blended foam becomes more viscous, but the degree of air incorporation is approximately the same. Generally, after adding the blended egg white foam to a gel formulation and heating, an amount of an organic acid such as citric acid or ascorbic acid is added to the gel formulation in molar equivalents relative to the amount of sodium caprylate. The effect of acidification is to lower the pH below the dissociation constant (pKa) of sodium caprylate to a pH at which the salt is converted to its water-insoluble free fatty acid oil. Sodium caprylate is closely dispersed with the defatted lecithin in the egg white before whipping and remains closely dispersed during and after whipping, as well as during the incorporation of the foam into the gel formulation and during the heating of the foam. When the formulation is acidified to a pH below the appropriate pH value, the closely dispersed sodium caprylate is converted to its free acid oil and associates with the lipophilic side of the lecithin dispersed together by phase attraction. The form of the lecithin dispersed together is similar to that of oil droplets, located at or at least very close to the air interface of the bubbles of the whipped egg white.

[0032] It will be understood that any functional ingredient that does not interfere with the whipping and foaming of the egg white can be directly included during the whipping process. Furthermore, incorporation at the air interface of the foam will enhance the delivery of any compatible ingredient due to the increased available dosage and improved release characteristics at the expanded surface area of the foam. The foamed egg white matrix may contain other additives, such as sweeteners, chelating agents, flavoring agents, coloring agents, modified vegetable gums or cellulose, or combinations of such additives that do not interfere with the foaming and whipping of the egg white. It will be readily appreciated that the additives included in the matrix should be selected such that they do not affect the properties of the matrix, do not exhibit substantial reactivity with the functional components in the matrix, and are stable during the preparation of the matrix. Sweeteners can be selected from a wide variety of suitable materials known in the art. Representative and non-limiting examples of sweeteners include, but are not limited to, sucrose, fructose, lactose, sorbose and glucose, sugars such as these, and glycerol, xylitol, sorbitol, lactitol and erythritol, sugar alcohol derivatives such as these. The ratio of egg white to the sugar and / or sugar derivative selected can be in the range of 1.0:0.1 to 2.0:10.0 or in the range of 1.0:5.0 to 1:1.

[0033] Metal salts and free metal ions such as magnesium, calcium, zinc, and iron are often problematic and can inhibit active functional components such as free fatty acids. To counteract the effects of salts and free ions, chelating agents can be added to the egg white prior to foaming or to other components in the gel scaffold. Suitable chelating agents include, but are not limited to, orthophosphates and polyphosphates such as disodium orthophosphate or dipotassium orthophosphate, disodium uridine monophosphate, sodium phytate, and sodium hexametaphosphate. Non-phosphate-based chelating agents include trisodium citrate and ethylenediaminetetraacetic acid. The content of the chelating agent can be 0.1% W / V to 5.0% W / V. Some chelating agents inhibit the growth of microorganisms by sequestering essential mineral metabolites, especially in environments where the chelating agent is available at very low concentrations. Usually, when mineral supply is replenished, the growth of microorganisms returns to normal. However, as illustrated herein, in certain embodiments, by including other functional components such as emulsions of free fatty acids, it has been unexpectedly found that they act synergistically with the chelating agent to inhibit the growth of microorganisms in the presence of excessive mineral supplements.

[0034] One of ordinary skill in the art will understand that in certain physiological environments, mineral concentrations are characteristically higher, and such physiological environments include blood, serum, mucus, and saliva that require divalent metal ions. For example, in the treatment of wounds, it may be desirable to lower the concentration of divalent ions such as calcium to inhibit blood clotting, and when a bactericidal effect is also desired, a combination of a chelating agent such as hexametaphosphate and a functional emulsion of free fatty acids may be of great utility. Similarly, it is well known that saliva is supersaturated with respect to calcium ions, and it is also well known that the non-selective deposition of calcium in dental plaque causes the tenacious adhesion of tartar and greatly increases the risk of gum disease. In formulations intended to promote oral health and / or treat or prevent oral diseases, it may be advantageous to use a calcium chelating agent to reduce tartar. When it is desirable to limit the formation of dental plaque including an antibacterial effect, a synergistic combination of hexametaphosphate and a functional emulsion of free fatty acids achieves significantly enhanced health benefits. Chelating agents such as polyphosphates are commonly used in skin care formulations and generally stabilize and prevent decomposition reactions catalyzed by divalent metal ions. For example, in the use of medicated cosmetics where it is desirable to obtain an additional antibacterial effect, a synergistic combination of polyphosphate and a functional emulsion of free fatty acids is particularly beneficial. An example of such a medicated cosmetic is a facial cream for acne, and a further example is a shampoo designed to improve infectious dandruff.

[0035] Suitable flavoring agents that can be added to the delivery system include both synthetic flavor oils and oils derived from various sources such as plants, leaves, flowers, fruits, nuts, etc. Representative flavor oils include spearmint oil, peppermint oil, cinnamon oil, and wintergreen oil (methyl salicylate). Other useful oils include, for example, artificial, natural or synthetic fruit flavors such as citrus oils including lemon, orange, grape, lime, and grapefruit, artificial, natural, or synthetic fruit essences including apple, strawberry, cherry, pineapple, banana, raspberry, and combinations thereof. The amount of flavoring agent used is usually determined by preferences for factors such as the flavor stock, flavor type, base type, and concentration / dilution of the desired strength. Generally, an amount of about 0.01% to about 5.0% by weight of the final product is useful. In certain embodiments of the present disclosure, vanilla is included in the matrix in an amount of about 1.5% as a flavoring agent. In another embodiment, the flavoring agent is added in an amount of about 0.03% to about 1.5%.

[0036] To add visual appeal, a food coloring suitable for use in food products may be included in the matrix. A wide variety of suitable food colorings are commercially available, for example, those manufactured by Warner Jenkins, St. Louis, Mo. When using a synthetic coloring agent in the matrix, the amount is in the range of about 0.01% to about 2% by weight. In certain embodiments of the present disclosure, the synthetic coloring agent is added to the matrix in an amount of about 0.03% to about 1% by weight. Due to the substantially uniform and complete dispersion of the functional components within the matrix, the delivery system is suitable for being divided into subunits. For example, if a single unit of the delivery system of the present disclosure is divided into three subunits, each subunit will contain one-third of the dosage of the original unit. Such division would not be possible in other delivery systems where the functional components are not uniformly dispersed.

[0037] In an embodiment, a foamed egg white matrix is used as part of a dual-action dental chew for dogs. The dual-action chew functions like a toothbrush and toothpaste, keeping a dog's mouth clean and protecting the dog's mouth from harmful bacteria. The dental chew includes two components, a flexible substrate and a filling. The flexible substrate is formed and designed to reduce plaque and tartar by mechanical action (scrubbing, abrasion) during chewing. Additionally, the chew substrate features a "reservoir" / cavity for the filling that contains functional ingredients. The filling includes a foamed egg white matrix and at least one functional ingredient, and the filling and functional ingredient are distributed in the mouth during chewing, providing a mechanical barrier that prevents bacteria from adhering to the surfaces (teeth, tongue, and gums) in the oral cavity. In an embodiment, the dental chew substrate is bone-shaped and has ridges and nodules on at least a portion of the exposed surface area to enhance mechanical clinics. In an embodiment, the functional ingredient in the filling includes an emulsion containing (a) one or more saturated or unsaturated free fatty acids having 4 to 22 carbon atoms or a pharmaceutically acceptable salt thereof, and (b) one or more defatted membrane lipids as an emulsifier for the free fatty acid or a pharmaceutically acceptable salt thereof.

[0038] Materials and Methods The construction of a foamed egg white foam with or without functional ingredients such as salts of free fatty acids and / or lecithin is based on an aqueous dispersion of egg white protein. The use of fresh egg white is not particularly applicable to industrial-scale processes, and commercially available powdered egg white not only offers much greater convenience but also provides an opportunity to vary the protein concentration in the foam. Egg white powder is available from many suppliers, including Canadian Inovatech (Abbotsford, BC, Canada). The egg white powder is rehydrated in water purified by reverse osmosis. A 10% w / w dispersion of egg white protein is made by including 10 grams of powdered egg white in 90 grams of water. Depending on the type of foam required and the amount of other ingredients to be mixed, dispersions of up to 40% protein can be rehydrated. As the protein concentration increases, the volume does not increase during whipping, but it is useful for other foaming methods including the use of hydrogen peroxide and catalase enzyme.

[0039] Whipped egg white forms a protein scaffold containing a significant amount of trapped air and needs to be fixed by heating to about 80 °C to denature the scaffold into an insoluble state. The water content facilitates heat transfer to the protein scaffold, and including other gelling agents (hydrocolloids) facilitates control of the physical properties of the residual moisture. Hydrocolloids are hydrophilic polymers of plant, animal, microbial, or synthetic origin and are either naturally present or added to aqueous food products for various reasons due to the unique texture, structure, and functionality of the hydrocolloid. Generally, hydrocolloids are used not only for thickening, gelling, and / or heat resistance but also for water-binding and sensory acceptability. Hydrocolloids can also be used to inhibit crystallization while simultaneously improving and / or stabilizing the texture of the food. Examples of hydrocolloids include, but are not limited to, starch, tragacanth, gluten, fumed silica, polyethylene glycol, cellulose and cellulose derivatives, gelatin, collagen, mucin, pectin, gum arabic, guar gum, gum acacia, karaya gum, locust bean gum, xanthan gum, carrageenan, agar, gellan, and / or sodium alginate, and combinations thereof.

[0040] The selection of the hydrocolloid to be used in the matrix depends on the pH of the matrix and the texture and consistency required for the final product. The type of hydrocolloid used will also affect the setting temperature of the matrix. For example, the use of a gelatin / gellan mixture or a gelatin / pectin mixture provides a setting temperature of approximately 35°C, while the use of carrageenan or locust bean gum results in a setting temperature close to 60°C. The use of agar results in a setting temperature close to 45°C. Thus, the selection of the hydrocolloid for use in the matrix also depends on the nature of the functional components included in the delivery system. Functional components that are unstable at higher temperatures require the selection of a hydrocolloid or mixture thereof with a low setting temperature, while more stable functional components can be used with a hydrocolloid having a higher setting temperature.

[0041] In certain embodiments of the present disclosure, the matrix includes gelatin. The term "gelatin" refers to a heterogeneous mixture of water-soluble proteins of high average molecular weight derived from collagen-containing parts of animals such as skin, bone, and ossein by hydrolysis, usually acid hydrolysis or alkaline hydrolysis. Different types of gelatin can be prepared by changing the processing parameters. Gelatin is generally defined using the "bloom value," which indicates the strength of the gel formed under certain conditions in which gelatin is used. In confectionery production, if a hard gel is desired, gelatin with a higher bloom value is used. Conversely, if the final product needs to be more fluid, gelatin with a lower bloom value is used. The water retention capacity of gelatin alone is lower than that of a combination of gelatin with other hydrocolloids such as gellan or pectin, and in order to achieve the desired gelation / texture of the matrix, a larger amount of gelatin may be required. When the hydrocolloid in the matrix of the present disclosure includes gelatin, generally, the bloom value (BL) is about 100 to 300 BL.

[0042] In certain embodiments, the bloom value is about 260 BL. In other embodiments, a mixture of gelatin having different bloom values is used. As shown above, gelatin can be combined with one or more other hydrophilic colloids to impart slightly different properties to the matrix. For example, a combination of gelatin and agar, a combination of gelatin and pectin, or a combination of gelatin, agar and pectin provides a good texture to the matrix. Other combinations of hydrophilic colloids are also contemplated, for example, but not limited to, a combination of agar and pectin. When a combination of gelatin and agar is used in the preparation of the matrix, typically the gelatin:agar ratio ranges from about 1:1 to about 10:1. Such relative amounts provide a sticky structure to the delivery system. In certain embodiments of the present disclosure, a combination of gelatin and agar is used in the preparation of the matrix at a gelatin:agar ratio of about 1:1 to about 3:1.

[0043] In embodiments, the total amount of hydrophilic colloid contained in the matrix is generally from about 0.1 wt% to about 7.0 wt%. In certain embodiments, the total amount of hydrophilic colloid in the matrix is from about 0.5 wt% to about 6.8 wt%. In other embodiments, the total amount is from about 1.0% to about 6.0%. In other embodiments, the total amount is from about 2.0% to about 6.0%, from about 4.0% to about 6.0%, from about 5.0% to about 6.0%, and from about 6.0% to about 7.0%. In embodiments, the ratio of whipped egg white to the selected gelling agent can range from 2:1 to 0.2:10, or from 0.1:1 to 1:1. In other embodiments, the ratio of egg white to the gelling agent can range from 0.01:10 to 1.0:10, or from 1.0:10 to 10:1. A suitable grade of gelatin is 260 bloom, 40 mesh and is available from PB Leiner (Belgium), and food grade agar and other gelling agents are available from many suppliers including Special Ingredients Ltd. (Chesterfield, UK). The influence of the gelling agent on the physical stability and release characteristics of the final formulation in actual use must be considered.

[0044] In embodiments, other components used in formulations containing a foamed egg white matrix include capric acid or sodium caprate available from Merck Chemicals. In embodiments, the ratio of capric acid to egg white can range from 0.01:10.0 to 1.0:10, or from 0.1:1.0 to 1.0:1.0. In embodiments, other components used in formulations containing a foamed egg white matrix include lecithin. A suitable grade of purified lecithin is available from Lipoid AG (Zurich, Switzerland). In embodiments, the ratio of lecithin to egg white can range from 0.01:10.0 to 1.0:10 or from 0.1:1.0 to 1.0:1.0.

[0045] Assay of Functional Efficacy It should be understood that the present disclosure herein relates to the delivery of a variety of functional components that provide enhanced utility in human and animal healthcare, including but not limited to therapeutics, prophylactics, and nutraceuticals. To illustrate the utility of the foamed egg white-based formulations, the following examples use the antibacterial emulsion disclosed in Folan (U.S. Patent Application No. 15 / 384,372). This functional component exerts a dual antibacterial effect by restricting the attachment of microbial species and reducing the viability of the microbial species via a second bactericidal / microbistatic effect. For purposes of comparison, an assay of the bactericidal / microbistatic effect is used herein, and the method is described below. The assay is a standard microbial suspension test in which a known concentration of late-log-phase bacteria, yeast, or fungi is inoculated into a fixed volume or mass of test substance, blank, or control. After a set period, a neutralizing solution is added to stop the antibacterial effect, and the number of surviving microorganisms is counted by serial dilution and plate counting. The counting procedure is a standard and fundamental microbiological procedure for counting viable microorganisms and will be well known to those skilled in the art.

[0046] In a typical form of the assay, the method requires inoculating 0.1 mL of an 18-hour (late-log-phase) bacterial culture into 1 gram or 1 mL of the test sample, followed by vigorous stirring to mix. After the elapse of a predetermined exposure time, 9.0 mL of neutralizing buffer is added and mixed. This has the effect of stopping the bactericidal effect and enables a reliable estimate of the percentage of kill obtained by the test sample during the period between inoculation and neutralization. Typically, the exposure time ranges from 30 seconds to 30 minutes and may extend to several hours if time is required to measure the effect. To count the remaining viable cells and thereby calculate the percentage of kill, the number of viable cells in the inoculum is determined by serial dilution and plate counting. Appropriate blanks and controls are used to ensure the validity of the neutralization procedure and to allow for any interference from other constituents in the test sample.

[0047] In the assays described herein, the test organism is Staphylococcus aureus NCTC8325-4 (National Collection of Type Cultures, Public Health England, Porton Down, Salisbury, UK), a standard indicator bacterium known for its robust biofilm-forming ability. The stock solution of the bacterium is usually stored at -80 °C in beads in 50% glycerol. When a viability / bactericidal assay is required, a small aliquot from the stock solution is plated onto an appropriate nutrient agar, grown, and subcultured to ensure purity. When a broth culture is required, inoculate a 250 mL Erlenmeyer flask containing 100 mL of broth with a transfer loop from a pure agar culture and incubate the Erlenmeyer flask at 37 °C with constant agitation in a rotary incubator.

[0048] For the culture of the indicator bacterium, it is common to use Brain Heart Infusion (BHI) broth and agar, or Tryptone Soya agar or broth (TSB), both of which are commercially available from Oxoid (UK). The dilution buffer and neutralization buffer used in this method are phosphate-buffered saline (PBS) containing 137 mM sodium chloride, 2.7 mM potassium chloride, and 10 mM phosphate. As a neutralizing agent, 0.5% histidine, 3% polysorbate Tween80 (an anionic surfactant), and 0.3% lecithin are added to the PBS. Such "neutralizing" agents are defined in the EU guidelines on ISO certification of bactericidal efficacy and have been verified to be suitable for neutralizing free fatty acids at the concentrations used herein. The test samples prepared in the following examples are assayed by first dissolving or dispersing a measured amount of the sample in a measured amount of sterile water. Typically, 1 gram of the sample is macerated in 1 gram of water. This represents a 50% dilution of the sample and a loading of the effective amount of the sample. The macerated sample is inoculated with 1 mL of an 18-hour (late log phase) culture of the indicator bacterium. After stirring and culturing at 37 °C for a certain period of time, 9 mL of neutralization buffer is added and the mixture is inverted and mixed. By serial dilution and plate counting, the number of viable cells in the test sample after culturing and neutralization is measured, and this viable cell count is compared, by the exact same method, with the number of viable cells in a 1.0 mL control inoculum treated with the test sample or a blank test sample containing no functional ingredient. Typically, by culturing the indicator microorganism overnight, a viable cell count of more than 8 logs per mL (1.0×10 8 or 100,000,000) per mL is included. Typically, with the 2% W / W dose loading free fatty acid emulsion used in the following examples, a reduction in viability of more than 90% or 1 log is achieved with a 30-second exposure, and it is not uncommon to see a reduction of more than 6 logs (99.9999%) in 5 minutes.

Example

[0049] The delivery system and the method of making such a delivery system are merely illustrative, and to those skilled in the art, other formulations and methods will be apparent, and such other formulations and methods are intended to be included within the scope of the present invention. Example 1 - Egg white / gelatin / sorbitol formulation using an oil-in-water emulsion as a functional ingredient Table 1: Foamed egg white matrix formulation of Example 1

Table 1

[0050] A foamed egg white matrix containing a functional emulsion was prepared according to the following process. (a) Component 1 (purified water), Component 2 (citric acid), Component 3 (egg white), and Component 4 (gelatin) from Table 1 were combined in the stated amounts in a suitable container at room temperature and left for about 30 minutes to fully hydrate the gelatin. (b) Using a suitable weighing device with a whisk, the mass was carefully beaten / whisked for approximately 5 minutes to obtain a foam mass that maintained its shape when pulled up (a firm, solid peak). (c) While continuing to stir the mass (using a water bath or double boiler), the mass was heated to about 80 °C using a suitable thermocouple in the foam. (d) Component 5 (sorbitol) was added in the stated amount in Table 1 and stirred. The endothermic solubilization of sorbitol cooled the foam mass to approximately 60 °C. (e) The temperature was set / maintained at 60 °C (e.g., using a water bath / double boiler), and the foam mass was kept at this temperature. (f) Component 6 (flavoring) was added in the stated amount in Table 1 and stirred. (g) Component 7 (functional emulsion) was added in the stated amount in Table 1 and stirred. The foam mass could be maintained at 60 °C for up to 5 hours without significant deterioration. The foam mass can also be cooled when dispensed into a mold to form a hard and elastic material.

[0051] Assay of antibacterial effect: The total mass of the formulation in Example 1 was 279.5 grams and contained 4 grams of the functional emulsion (1.4%). The functional emulsion contained 10% free caprylic acid in the oil phase, and thus the concentration of free caprylic acid in the formulation of Example 1 was 0.14%. The antibacterial assay described in the section on materials and methods above gave the following results. TIFF0007717075000002.tif31145

[0052] Example 2 - An egg white / gelatin / agar formulation using a water-in-oil emulsion as a functional ingredient In this example, a combination of gelatin and agar was used to adjust the solubility and heat resistance of the whipped egg white preparation. Gelatin begins to melt at temperatures within the range of 35°C, and the stability of the final preparation having only gelatin as a gelling agent is liable to flow and deform when the storage temperature exceeds the melting temperature of gelatin (35°C). Agar melts at 80°C and is a polysaccharide gel that remains liquid at temperatures up to 45°C. The unique hysteresis of agar can be used in combination with gelatin to improve the thermal stability of the preparation without losing the low-temperature solubilization property of gelatin. In this example, in order to prevent over-drying, glycerol was added to retain residual water by its wetting effect.

[0053] Table 2: Whipped egg white matrix preparation of Example 2 [Table 2]

[0054] A whipped egg white matrix containing a functional emulsion was prepared according to the following process. (a) Component 1 (purified water), Component 2 (citric acid), Component 3 (agar), and Component 4 (gelatin) from Table 2 were combined in the appropriate amounts in a suitable container, left for about 30 minutes to fully hydrate, and then the mixture was heated to about 90°C. The temperature was confirmed using a thermocouple in the mass. (b) In a separate container, Component 5 (purified water) and Component 6 (glycerol) from Table 2 were combined in the appropriate amounts in a suitable container. (c) Using a suitable weighing device with a whisk, the described amount of Component 7 (20% egg white) from Table 2 was carefully whisked / tapped in a suitable container for approximately 5 minutes to obtain a mass of foam that maintained its shape when pulled upwards (a firm, solid peak). (d) When the mixture from step (a) reached 90°C and the agar had melted, the glycerol-water mixture of step (b) was added and stirred well to mix. When the temperature dropped to approximately 70°C, step (e) was carried out immediately. (e) 50 grams of the mixture from step (c) was added to the mixture from step (d) and stirred vigorously. Then, stirring was continued while heating to a temperature exceeding 80°C, and when the temperature exceeded 80°C, heating was stopped and / or the mixture was removed from the heating. (f) Component 8 (flavoring agent) from Table 2 was added in the stated amount and stirred. (g) Component 9 (functional emulsion) from Table 2 was added in the stated amount and stirred. The foam mass could be maintained at 60°C for up to 5 hours without significant deterioration. The foam mass can also be cooled when dispensed into a mold to form a hard and elastic material.

[0055] Assay of antibacterial effect: The total mass of the formulation in Example 2 was 471.6 grams and contained 10 grams of the functional emulsion (2.12%). The concentration of caprylic acid in the functional emulsion was 10%, and thus the concentration of free caprylic acid in the formulation was 0.17%. The antibacterial assay described in the section on the above materials and methods gave the following results. TIFF0007717075000004.tif31145

[0056] Example 3 - Construction of a formulation containing a precursor of a functional emulsion in egg white foam In this example, a combination of foamed egg white containing lecithin and sodium caprylate as precursors of the functional emulsion disclosed in Folan (U.S. Patent Application No. 15 / 384,372) was constructed. After a heating step using an organic acid to convert inactive water-soluble sodium caprylate to active oil-soluble caprylic acid, the precursor was converted to the active form of the emulsion. Apart from the fact that it is not necessary to construct the functional emulsion separately, by incorporating the precursor into the egg white foam before heating the egg white foam, it is much more certain that the functional components will be concentrated at the foam-air interface after cooling. Adding the fully formed emulsion separately depends on the movement driven by the counter-repulsion that concentrates the oil droplets on the surface of the foam bubbles.

[0057] Table 3: Foamed Egg White Matrix Preparation of Example 3 [Table 3]

[0058] A foamed egg white matrix containing a precursor to a functional emulsion was prepared according to the following process. (a) Component 1 (water) and Component 2 (lecithin) from Table 3 were combined in the stated amounts in a suitable container at room temperature and left to hydrate for about 10 minutes. (b) Component 3 (sodium caprylate) from Table 3 was added in the stated amount and allowed sufficient time to completely solubilize before proceeding to the next step. (c) Component 4 (egg white powder) from Table 3 was added in the stated amount, wetted completely using a spatula, and left to hydrate completely for about 30 minutes. (d) In a separate container, Component 5 (purified water), Component 6 (agar), and Component 7 (gelatin) from Table 3 were combined in the stated amounts, left to hydrate completely for about 30 minutes, and subsequently the mixture was heated to about 90 °C. The temperature was confirmed using a thermocouple in the mass. (e) While raising the temperature of the mixture from step (d) using a suitable weighing device with a whisk, the completely hydrated composition from step (c) was whisked / whipped for approximately 5 minutes and pulled upwards to obtain a foam mass that retained its shape (a firm, solid peak forming Component 10). (f) When the mixture from step (d) reached 90 °C and the agar had melted, in a separate container, Component 8 (purified water) and Component 9 (glycerol) from Table 3 were combined in the stated amounts, added to the mixture from step (d), and stirred well. When the temperature dropped to approximately 70 °C, step (g) was carried out immediately. (g) While heating, 50 grams of the mixture from step (e) (Component 10) was added to the mixture from step (d) and stirred vigorously. Then, stirring was continued until a temperature above 80 °C was reached, and when above 80 °C, heating was stopped and / or the mixture was removed from the heat. (h) Component 11 (flavoring) from Table 3 was added in the stated amount and stirred to dissolve. (i) Add component 12 (citric acid powder) from Table 3 in the stated amount, stir well, leave for sufficient time to dissolve, check the pH, and confirm that the pH is less than 5.0. The foam mass could be maintained at 60 °C for up to 5 hours without significant deterioration. The foam mass can also be cooled when dispensed into a mold to form a firm and elastic material.

[0059] Antibacterial effect assay: The total mass of the formulation in Example 3 was 454.2 grams and contained 0.736 grams of sodium caprylate (0.16%) in 50 grams of foamed egg white. The molecular weight of sodium caprylate is 166.19 and the molecular weight of caprylic acid is 144.21, with a conversion factor of 1.15. Thus, for acidification, when converting all of the sodium caprylate dose load to free caprylic acid, the concentration of free caprylic acid in the formulation was 0.14%. The antibacterial assay described in the Materials and Methods section above gave the following results. TIFF0007717075000006.tif31145

[0060] Example 4 - Alternative method for creating egg white foam In situations where a suitable whisk is not readily available, hydrogen peroxide and catalase enzyme can be used to create a sufficient protein foam. Gelatin fully hydrated at room temperature and a more concentrated egg white protein are required. Hydrogen peroxide is available as 8%, 16% and 32% solutions, but higher concentrations pose a risk of significant chemical burns if accidentally splashed on human skin. The optimal amount of hydrogen peroxide varies depending on the concentration in the solution and the ambient temperature. Catalase enzyme is commercially available and is also permitted for food use. A very small amount of the enzyme is required to activate the decomposition of peroxide, which produces a relatively large amount of oxygen dispersed throughout the mass of egg white gelatin. Stirring must continue to maintain the foam and heat cooking should be started as soon as the peroxide reaction has ceased.

[0061] Table 4: Foamed Egg White Matrix Formulation of Example 4 [Table 4]

[0062] A foamed egg white matrix containing a functional emulsion was prepared according to the following process. (a) Component 1 (purified water) and Component 2 (gelatin) from Table 4 were combined in the stated amounts in a suitable container at room temperature and left for about 30 minutes to fully hydrate the gelatin. (b) 40 grams of egg white was added to 60 grams of water, and the powder was carefully wetted using a spatula and left for about 30 minutes to fully hydrate the powder to prepare Component 3. (c) The mixtures from steps (a) and (b) were combined and blended together. (d) The stated amount of Component 4 (hydrogen peroxide) from Table 4 was added to the mixture from step (c) and blended well, followed by the addition of the stated amount of Component 5 (catalase) from Table 4 and blended well. The foaming reaction started within 1 minute and continued for approximately 5 minutes, during which the foam mass was continuously stirred. (e) Heating was started while stirring continuously, and a suitable thermocouple was used in the foam to raise the foam mass to 80°C. (f) The stated amount of Component 6 (sorbitol) from Table 4 was added and stirred. The endothermic solubilization of sorbitol cooled the foam mass to approximately 60°C. (g) The temperature of the foam mass was set / maintained at 60°C (using a water bath / water bath heater). (h) The stated amount of Component 7 (flavor) from Table 4 was added and stirred. The foam mass could be maintained at 60°C for up to 5 hours without significant deterioration. The foam mass can also be cooled when dispensed into a mold to form a hard and elastic material.

[0063] Assay for Antibacterial Effect: The total mass of the formulation in Example 4 was 263.7 grams and contained 4 grams of a functional emulsion (1.5%). The functional emulsion contained 10% free caprylic acid in the oil phase, and thus the concentration of free caprylic acid in the formulation of Example 4 was 0.15%. The antibacterial assay described in the Materials and Methods section above gave the following results. TIFF0007717075000008.tif31145

[0064] Example 5 Egg white / gelatin / agar / chelating agent formulation using a water-in-oil emulsion as a functional ingredient Sodium hexametaphosphate is incorporated as a chelating agent, together with increased citric acid, to illustrate counteracting the inherent alkalinity of the formulation. Table 5: Foamed egg white matrix formulation of Example 5

Table 5

[0065] A foamed egg white matrix containing precursors to the functional emulsion was prepared according to the following process. (a) Component 1 (purified water), Component 2 (citric acid monohydrate), and Component 3 (agar) from Table 5 were combined in the stated amounts in a suitable container at room temperature, left to hydrate for about 10 minutes, and then heated to 80 °C. The temperature was confirmed using a thermocouple in the mass. (b) In a separate container, Component 4 (gelatin), Component 5 (sorbitol), and Component 3 (sodium caprylate) from Table 5 were combined in the stated amounts and blended as a dry powder. (c) Using a suitable weighing device with a whisk, the stated amount of Component 6 (20% egg white) from Table 5 was whisked / whipped in a suitable container for approximately 5 minutes to obtain a mass of foam that retained its shape when pulled upwards (a firm, solid peak). (d) When the mixture from step (a) reached a temperature of approximately 80 °C and the agar had melted, the powder mixture from step (b) was added while stirring continuously. When the temperature dropped to approximately 60 °C, step (e) was carried out immediately. (e) 45 grams of the mixture from step (c) was added to the mixture from step (d) and stirred vigorously. Then, stirring was continued while heating to a temperature exceeding 80 °C, and when the temperature exceeded 80 °C, heating was stopped and / or the mixture was removed from the heating. (f) The described amount of component 7 (flavoring) from Table 5 was added and stirred, followed by adding the described amount of component 8 (sodium hexametaphosphate) from Table 5 and stirring, and then adding the described amount of component 9 (functional emulsion) from Table 5 and stirring. It was confirmed that the pH was less than 5.0. The mass of the foam mass could be maintained at 60 °C for up to 5 hours without significant deterioration. The foam mass can also be distributed into a mold and cooled when forming a hard and elastic material.

[0066] In other embodiments, if necessary, an equal amount of erythritol or another polyol can be used instead of sorbitol. Assay for antibacterial effect: The total mass of the formulation in Example 5 was 520.6 grams and contained 10 grams of the functional emulsion (1.9%). Using the antibacterial assay described in the section on the above materials and methods, the antibacterial effect, similar to Example 2, was a 1.6 logarithmic decrease in the survival rate after 1 minute of exposure. Table 6: Summary of antibacterial efficacy

Table 6

[0067] Except for Example 3, while allowing for experimental error, the differences in the percentage of logarithmic decrease in Examples 1, 2, and 4 were more or less consistent with the caprylic acid content. It should be noted that Example 3 had the same concentration of caprylic acid as Example 1 and showed an effect of more than 34%. Although it is not desirable to be restricted by an explanation, the increase in efficacy in Example 3 compared to Example 1 is suggested to be due to the improved availability and release of the dosage on the amplified surface of the whipped egg white due to the finer dispersibility of the in situ formation of caprylic acid compared to the droplet form of caprylic acid when incorporated as an emulsion.

[0068] Example 6: Synergistic antibacterial effect of polyphosphates when combined with functional emulsions of free fatty acids The inclusion of hexametaphosphate as an example of a polyphosphate used as a chelating agent is shown in Example 5, which includes sodium hexametaphosphate ("SHMP" or "sodium HMP"). When evaluating the antibacterial effect of the formulation in Example 5, it was unexpectedly found that the combination of the functional emulsion of free fatty acids acted synergistically with hexametaphosphate. All mineral chelating agents, especially when essential minerals such as calcium, magnesium, zinc, and iron in the medium are limited, exert a growth inhibitory effect on bacteria and achieve this effect by sequestering the essential minerals. This growth inhibitory effect by the chelating agent can be easily eliminated by supplementing the growth medium with essential minerals.

[0069] The functional emulsions of free fatty acids disclosed in U.S. Patent Application No. 15 / 384,372 will exhibit the strong antibacterial effects shown in Examples 1 to 5 of this application. It was unexpectedly found that the functional emulsions increase the growth inhibitory effect of polyphosphates and also increase the growth inhibitory effect even when calcium, which suppresses the effect of hexametaphosphate, is supplemented. To demonstrate the synergistic effect of the combination of the functional emulsion and hexametaphosphate, it is necessary to construct both formulations at their minimum inhibitory concentrations and formulations below their minimum inhibitory concentrations, and then combine the two formulations and measure an increase in effect greater than that expected to be additive. In this example, 2% W / W of a mixed capric / caprylic triglyceride (Miglyol 812N, manufactured by IOI Oleo, Germany) and 8% W / W of capric acid in the oil phase were used, and 1.56% W / W of lecithin and 0.15% Tween 80 were used as co-surfactants. The procedure disclosed in US Patent Application No. 15 / 384,372 was used to construct the formulation of the functional emulsion.

[0070] As described in the method, the test organism was Staphylococcus aureus NCTC 8325-4, and the flask culture was 100 mL of Luria-Bertani medium (LB broth) in a 250 mL Erlenmeyer flask. Since the mineral content in LB broth is clearer and more restricted, LB broth was used instead of brain heart infusion medium. A standard inoculum was grown as described in the method section and diluted with sterile saline to adjust the viable cell count to 1×10 6 . 0.1 mL of this dilution was used to aseptically inoculate 100 mL of the test medium (1×10 3 inoculum in the test flask). The minimum inhibitory concentration of the functional emulsion was determined using the agar dilution method, where the test organism was streaked on LB agar plates with gradually increasing dilutions of the functional emulsion and the growth was visually evaluated after incubation at 37°C for 24 hours. The results are shown in Table 7. Since some growth was detected even at 0.5%, the minimum growth inhibitory concentration can be considered to exceed 0.5%. The concentration of 0.375 had no inhibitory effect on growth, and this concentration was selected for further study in combination with hexametaphosphate.

[0071] Table 7: Minimum Growth Inhibitory Concentration of Functional Emulsion against Staphylococcus aureus NCTC8325-4 [Table 7]

[0072] To determine the minimum inhibitory effect of hexametaphosphate, each of a series of flasks containing 100 mL of LB broth was supplemented with hexametaphosphate in a concentration range of 0% W / W to 1% W / W, and each flask was inoculated with a standard inoculum to obtain a viable cell count of 1×10 3 . The flasks were cultured at 37 °C for 24 hours in a rotary incubator, and the growth at the end of 24 hours of culture was visually evaluated. As shown in the first row of Table 8 below, growth was apparent only in the flasks where the concentration of hexametaphosphate was zero, and growth was clearly inhibited at all concentrations of 0.05% and above. After visual evaluation, 0.5% sterile calcium chloride was added to all flasks and further culture was continued for 24 hours. Twenty-four hours after the addition of calcium chloride, sufficient growth was confirmed visually in all flasks with hexametaphosphate at a concentration of 0.27% or less. At hexametaphosphate concentrations of 0.5% and above, it remained inhibited. From this data, it can be understood that 0.27% hexametaphosphate inhibits growth unless at least 0.5% calcium chloride is supplemented to the medium (in this case, there is no inhibitory effect on growth).

[0073] Table 8: Effect of Sodium Hexametaphosphate on the Growth of Staphylococcus aureus in Liquid Culture [Table 8]

[0074] However, when the medium is further supplemented with 0.375% functional emulsion (a concentration at which the functional emulsion itself has no growth inhibitory effect), sufficient growth inhibition is restored. The synergistic effect when supplemented with a functional emulsion (an oil-in-water emulsion consisting of fine oil droplets of capric acid dispersed in water, stabilized with purified amphiphilic lecithin and any other components, e.g., co-surfactant, hereinafter referred to as "ML:8" in this specification) is exemplified by the data shown in Table 9 below.

[0075] Table 9: Synergistic action of ML:8 hexametaphosphate

Table 9

[0076] The first row in Table 9 is a control flask containing Luria-Bertani (LB) broth and a standard inoculum, and the final plate count shows sufficient growth with viable cell counts of more than 10 9 CFU / mL. The second row in Table 9 is the same LB broth containing the same inoculum supplemented with 0.375% functional emulsion, showing healthy growth at 12 hours and 24 hours, and the final plate count shows viable cell counts that are slightly 1 logarithm less compared to the control (a 1-log reduction). The third row in Table 9 is a control regarding calcium chloride, indicating that this supplementation has no effect on growth and the final plate count is the same as the control. The fourth row in Table 9 shows that 0.27% hexametaphosphate completely inhibits growth and the residual survival rate was 2×10 2 . This is essentially the inoculum of the bacteria in the inoculum that remains viable even when inhibited (a bacteriostatic effect, not a bactericidal effect). The fifth row in Table 9 is the same as the fourth row, supplemented with 0.5% calcium chloride. The inhibitory effect of hexametaphosphate is completely reversed, and it has the same final survival rate as the control in the row. The sixth row in Table 9 is the same as the second row, supplemented with 0.5% calcium chloride. The final survival rate decreased by one logarithm, the same as in the second row. The addition of calcium chloride increases or suppresses the effect of the functional emulsion at the concentration used in this example. The seventh row in Table 9 is a combination of the second row (no inhibition) and the fifth row (no inhibition), showing sufficient inhibition with a remaining survival rate of only 2×10 2 This indicates that through the test procedure, it is the bacteria in the inhibited inoculum that remain viable.

[0077] It can be concluded that sodium hexametaphosphate has no inhibitory effect on microbial growth under conditions of excessive calcium. Similarly, 0.375% functional emulsion has no inhibitory effect on microbial growth under the same conditions. The two components (functional emulsion and hexametaphosphate) act synergistically to completely inhibit microbial growth when combined under conditions of excessive calcium. A similar synergistic effect can be shown using other polyphosphates, including but not limited to disodium orthophosphate, uridine monophosphate, and sodium phytate. Using the procedures described to generate the data in Table 8, the critical values of disodium orthophosphate (0.75%) and sodium phytate (0.2%) when combined with 0.5% calcium chloride were determined. The fact that uridine monophosphate is not decisive at 1% suggests that its chelating property is not strong. Using a similar procedure, the critical values of non-phosphate chelating agents containing trisodium citrate and ethylenediaminetetraacetic acid when combined with 0.5% calcium chloride were 0.5% and 0.25%, respectively.

[0078] Note that the ionic bond of many chelating agents depends on pH, especially trisodium citrate, an organic acid salt that dissociates below pH 6.0. One of ordinary skill in the art will understand that the ratios of chelating agent / calcium chloride / functional emulsion provided in this example have been selected as the most appropriate for explaining the synergistic effect by comparative measurement. Although the measurement of the synergistic effect may be hindered by an excess of any of the components, the same synergistic effect is evident in all combinations of the same components.

[0079] Example 7 Another formulation containing a precursor of a functional emulsion in an egg white foam An exemplary formulation of the foamed egg white matrix has the composition disclosed in Table 10. Table 10: Exemplary foamed egg white matrix formulation of Example 7 [Table 10] In an embodiment, the sugar is saccharin. In an embodiment, the flavoring is vanilla. In an embodiment, the functional component is sodium HMP.

[0080] In certain embodiments, the delivery system comprises an egg white matrix formulation disclosed in Table 11. Table 11: Foamed egg white matrix formulation [Table 11]

[0081] In certain embodiments, the delivery system comprises an egg white matrix formulation disclosed in Table 12. Table 12: Foamed egg white matrix formulation [Table 12]

[0082] Example 8 Another alternative formulation containing a precursor of a functional emulsion in an egg white foam An exemplary formulation of a foamed egg white matrix has the composition disclosed in Table 13. Table 13: Exemplary foamed egg white matrix formulation of Example 8

Table 13

[0083] In an embodiment, the sugar is saccharin. In an embodiment, the flavoring agent is vanillin. In an embodiment, the functional component is sodium HMP. In other embodiments, no functional components other than the functional emulsion are added. In an embodiment, the functional emulsion consists of oil droplets of capric acid finely dispersed in water, and is an oil-in-water emulsion (hereinafter, referred to as "ML:8" in this specification) stabilized with purified amphiphilic lecithin and any other components, such as co-surfactants. In another embodiment, a functional emulsion is added as a mixture of precursors (hereinafter, referred to as "ML:8 precursor") containing sodium caprylate, lecithin, Lipoid S75, and water, and after a heating step of converting inactive water-soluble sodium caprylate to active oil-soluble capric acid using an organic acid, the functional emulsion is converted to the active form of the emulsion.

[0084] In certain embodiments, the delivery system comprises an egg white matrix formulation disclosed in Table 14. Table 14: Exemplary foamed egg white matrix formulation of Example 8

Table 14

[0085] In certain embodiments, the delivery system comprises an egg white matrix formulation disclosed in Table 15. Table 15: Exemplary foamed egg white matrix formulation of Example 8

Table 15

[0086] In certain embodiments, the delivery system comprises an egg white matrix formulation as disclosed in Table 16. Table 16: Exemplary Foamed Egg White Matrix Formulation of Example 8

Table 16

[0087] In certain embodiments, the delivery system comprises an egg white matrix formulation as disclosed in Table 17. Table 17: Exemplary Foamed Egg White Matrix Formulation of Example 8

Table 17

[0088] In certain embodiments, the delivery system comprises an egg white matrix formulation as disclosed in Table 18. Table 18: Exemplary Foamed Egg White Matrix Formulation of Example 8

Table 18

[0089] In certain embodiments, the delivery system comprises an egg white matrix formulation as disclosed in Table 19. Table 19: Exemplary Foamed Egg White Matrix Formulation of Example 8

Table 19

[0090] In certain embodiments, the delivery system comprises an egg white matrix formulation as disclosed in Table 20. Table 20: Exemplary Foamed Egg White Matrix Formulation of Example 8

Table 20

[0091] In one embodiment, the delivery system comprises an egg white matrix formulation disclosed in Table 21. Table 21: Exemplary Foamed Egg White Matrix Formulation of Example 8 [Table 21]

Claims

**Claim 1** A delivery system for a functional ingredient, comprising one or more functional ingredients substantially uniformly dispersed in a matrix, wherein the matrix comprises i) a foamed egg white foam containing 1 to 50% protein, ii) one or more heat-resistant and / or heat-sensitive gelling agents, iii) a pH adjuster, iv) one or more plasticizers and / or wetting agents, v) one or more waters, and a chelating agent, the delivery system as described above. **Claim 2** The delivery system according to claim 1, wherein the one or more gelling agents comprise agar. **Claim 3** The delivery system according to claim 1, wherein the one or more gelling agents comprise gelatin. **Claim 4** The delivery system according to claim 1, wherein the one or more gelling agents comprise pectin. **Claim 5** The delivery system according to claim 1, wherein the one or more gelling agents comprise at least two gelling agents selected from agar, gelatin, and pectin. **Claim 6** The delivery system according to claim 1, wherein the pH adjuster is citric acid. **Claim 7** The delivery system according to claim 1, wherein the one or more functional ingredients comprise a functional emulsion. **Claim 8** The delivery system according to claim 1, comprising two or more functional ingredients. **Claim 9** The delivery system according to claim 1, wherein the chelating agent is a polyphosphate. **Claim 10** The delivery system according to claim 9, wherein the polyphosphate is sodium hexametaphosphate. **Claim 11** The delivery system according to claim 1, wherein the one or more functional ingredients are selected from the group consisting of drugs, botanicals, nutritional supplements, vitamins, minerals, enzymes, hormones, proteins, polypeptides, and antigens. **Claim 12** The delivery system according to claim 1, further comprising a sweetener, a buffer, a natural or artificial flavor, a coloring agent, or a combination thereof. **Claim 13** A dual-action dental chew for dogs, wherein the dental chew comprises a flexible substrate and a filling, the filling comprising the delivery system according to claim 1. **Claim 14** The dual-action dental chew for dogs according to claim 13, wherein the flexible substrate is formed and designed to reduce dental plaque and tartar by mechanical action (scrubbing, abrasion) during chewing, and the chew substrate features a "reservoir" / cavity for the filling. **Claim 15** The delivery system comprises a functional ingredient including an emulsion, the emulsion comprising (a) one or more saturated or unsaturated free fatty acids having 4 to 22 carbon atoms or a pharmaceutically acceptable salt thereof, and (b) one or more defatted membrane lipids as an emulsifier for the free fatty acid or a pharmaceutically acceptable salt thereof, the dual-action dental chew for dogs according to claim 13.

16. A method of using the delivery system according to claim 1 for oral administration of a functional ingredient to a non-human animal in need of one or more functional ingredients, the method comprising the step of administering the delivery system to the non-human animal in need thereof.

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