An expanded foam for delivering a functional ingredient

Abstract

The present disclosure provides a delivery system for functional ingredients (e.g., pharmaceuticals, nutritional supplements, botanical therapeutics, and vitamins) comprising an ingestible matrix within which the functional substance is substantially uniformly and completely dispersed. The matrix comprises a foam derived from physically shearing egg white to achieve an expanded available dose and improved release characteristics of the functional ingredient onto skin and mucosal surfaces for health care purposes. The present disclosure also provides methods of making and using the delivery system.

Description

[0001] Field of the Disclosure

[0002] The present disclosure relates to the field of health components or functional ingredients, including pharmaceutical and nutraceutical, and systems for delivering such health components or functional ingredients.

[0003] Background of the Disclosure

[0004] Functional ingredients, including pharmaceutical products designed to treat or prevent infectious diseases, such as antibiotics, antiseptics and topical disinfectants, and nutraceuticals designed to promote the health and well-being of humans and animals, including vitamins, amino acids and essential fatty acids, have seen a popular increase, evidenced by the tremendous growth of the industries involved in their manufacture, production and distribution.

[0005] Among the different types of functional ingredients, many are water soluble, some are oil soluble only, and a few are amphiphilic ingredients that exhibit partial solubility in both oil and water in a manner analogous to surfactants.

[0006] The solubility of any functional ingredient significantly influences the appropriate manner of its delivery to the human or animal body, particularly in oral applications, where the functional ingredient is intended to affect a response on or in the gastrointestinal tract, and topical and mucosal applications, where the functional ingredient is intended to affect a response on or in the skin or mucosa, and by extension to the structures emanating from these surfaces, such as hair, nails and teeth.

[0007] Formulations of poorly soluble functional ingredients typically include excipients designed to promote solubility, absorption and / or residence time on the intended surface. The available dose of any functional ingredient in such formulations is also limited by the amount of formulation that can be applied to the intended surface, and the migration or release of the functional ingredient from the formulation onto or into the intended surface.

[0008] Several different delivery systems have been developed in an attempt to improve the method of delivering various supplements or functional ingredients. For example, a number of encapsulation formulations have been developed that encapsulate or retain the functional ingredient in various glassy, sintered or chewy confectionery type matrices. Typically, a confectionery is used as a solid continuous matrix for the active ingredient or supplement. The active ingredient is delivered according to the dissolution rate of the confectionery matrix, which imparts a solid taste in the mouth. Crushing the confectionery is a consumer's solution to accelerate the release of the active ingredient, which can not be desirable as tooth problems can arise and / or the release rate of the active ingredient incorporated therein is no longer optimal. Depending on the method of manufacturing the confectionery matrix, the active ingredient can suffer from deterioration or damage due to heating and / or mechanical stress during the manufacturing process. Typically, the high rate of deterioration caused by the intensive processing conditions is compensated by an excess of the active ingredient in the confectionery matrix, however, this is an expensive method that results in a waste of a large amount of the active ingredient. The "solid" taste that a compressed tablet or glassy matrix can provide in the mouth can also be seen as not very appealing in the context of delivering an active ingredient, especially if the taste is unpalatable.

[0009] Accordingly, there is a need to provide a system for the effective delivery of functional ingredients with improved solubility and release characteristics, in particular for amphiphilic and oil-soluble functional ingredients.

[0010] SUMMARY

[0011] According to an aspect of the present disclosure, there is provided a delivery system for one or more functional ingredients, wherein the delivery system represents an expanded foam matrix, wherein the one or more functional ingredients are substantially homogenously dispersed, the matrix comprising:

[0012] i) a protein component comprising a protein concentration of 1-50%;

[0013] ii) one or more heat resistant and / or heat sensitive gelling agents;

[0014] iii) a pH adjuster;

[0015] iv) one or more plasticizers and / or humectants; and

[0016] v) one or more water sources,

[0017] wherein the delivery system is solid at room temperature.

[0018] In another aspect of the present disclosure, there is provided the use of a delivery system for one or more functional ingredients for oral administration to an animal in need thereof.

[0019] In embodiments, the present disclosure provides a method for improving oral health in a companion animal.

[0020] In one embodiment, the present disclosure provides a method of maintaining or improving oral health in a subject in need thereof, the method comprising administering to the subject an effective amount of an oral antimicrobial composition, wherein the oral antimicrobial composition comprises: (a) one or more saturated or unsaturated free fatty acids or pharmaceutically acceptable salts thereof; and (b) one or more delipidated membrane lipids as an emulsifier for the free fatty acids or salts thereof.

[0021] In embodiments, the present disclosure provides methods for oral delivery of a health-related composition to a companion animal, the health-related composition comprising one or more health components for oral health, joint health and mobility, cardiovascular health, bone health, skin health, gut health, anti-stress / calming or other behavioral conditions, anti-parasite agents such as anti-flea or anti-tick agents, or vaccines.

[0022] Further variations and advantages of the present disclosure will become apparent from a detailed description of the disclosure in conjunction with the accompanying examples.

[0023] DETAILED DESCRIPTION

[0024] It should be noted that in the present disclosure and particularly in the claims, terms such as "comprising," "including," containing," and "having" shall be understood as allowing for "including," "comprising," "including" to be comprised of zero "only," and terms such as "consisting essentially of and "consisting of shall allow for the explicit recitation of such elements, but exclude elements found in the prior art or affecting the basic or novel characteristic of the present disclosure.

[0025] Unless otherwise indicated, technical terms, including scientific and medical terms, have the meanings that are commonly understood by one of ordinary skill in the art to which this disclosure belongs. Definitions of common terms in molecular biology can be found in Benjamin Lewin, Genes V., published by Oxford University Press (1994); Kendrew et al. (eds.), The Encyclopedia of Molecular Biology, published by Blackwell Science Ltd. (1994); and Robert A. Meyers (ed.), Molecular Biology and Biotechnology: A Comprehensive Desk Reference, published by VCH Publishers, Inc. (1995).

[0026] As used above, and throughout the specification herein, unless otherwise specified, the following terms have the below meanings: The singular terms "a," "an," and "the" include plural referents unless the context clearly indicates otherwise. Similarly, the word "or" is intended to mean any one member of a particular list or any combination of members of the list.

[0027] It should also be understood that, although the terms first, second, etc. can be used herein to describe various elements, these elements should not be limited by these terms. These terms are only used to distinguish one element from another. For example, a first item can be termed a second item, and, similarly, a second item can be termed a first item, without departing from the scope of the present disclosure. Unless otherwise specified herein, all methods or processes described herein can be performed in any suitable order.

[0028] The term "about," as used in the present application, means approximately, in the range of, roughly, or around. When the term "about" is used in conjunction with a numerical range, it modifies that range by extending the boundaries to include numbers that are outside the numerical bounds and that are near the specified range that could reasonably affect the end result expected by one of ordinary skill in the art. In general, the term "about" is used herein to modify a numerical value up to 10% above and below the stated value. In one aspect, the term "about" means plus or minus 10% of the numerical value of the number with which it is being used. Thus, about 50% means in a range of 45% to 55%.

[0029] Numerical ranges as used herein are inclusive of the numbers and fractions within the range (e.g., 1 to 5 includes 1, 1.5, 2, 2.75, 3, 3.90, 4, and 5). It should further be understood that all numbers and fractions are assumed to be modified by the term "about" even if the term "about" is not expressly stated.

[0030] The terms "subject," "patient," "user," and "individual" are used interchangeably herein to refer to a human or an animal.

[0031] The terms "animal" and "companion animal" are used herein to include all mammals, avians, and fish. Animals used herein can be selected from the group consisting of: equines (e.g., horses), canids (e.g., dogs, wolves, foxes, coyotes, big cats), felines (e.g., lions, tigers, domestic cats, wild cats, other big cats, and other felines including cheetahs and lynx), bovines (e.g., cattle), swine (e.g., pigs), ovines (e.g., sheep, goats, alpacas, bison), avians (e.g., chickens, ducks, geese, turkeys, quail, pheasants, parrots, finches, hawks, crows, ostriches, cassowaries, and rheas), primates (e.g., prosimians, tarsiers, monkeys, gibbons, apes), humans, and fish.

[0032] The use of any and all examples, or exemplary language (e.g., "such as") provided herein, only intends to better illuminate the disclosure and does not pose a limitation on the scope of the disclosure unless otherwise claimed. No language in the specification should be construed as indicating any non-claimed element as essential to the practice of the disclosure.

[0033] The term "carrier" refers to a diluent, adjuvant, excipient, or vehicle, with which the active / functional ingredient is administered. Such a pharmaceutical carrier can be a sterile liquid, such as water and oils, including those of animal, vegetable or synthetic origin, such as peanut oil, soybean oil, palm oil, mineral oil, sesame oil and the like. Water or aqueous saline solutions and aqueous dextrose and glycerol solutions are preferred as carriers, particularly for injectable solutions. Alternatively, the carrier can be a solid dosage form carrier including, but not limited to, one or more of binders (for compressed tablets), glidants or lubricants, 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); Liberman et al., Eds., Pharmaceutical Dosage Forms, Marcel Decker, New York, N.Y.; and Kibbe et al., Eds., Handbook of Pharmaceutical Excipients, American Pharmaceutical Association, Washington.

[0034] The term "effective amount" or "effective dose" as used herein refers to an amount of a health component known in the art to confer a health benefit; wherein the effective amount in the composition is high enough to provide the desired effect or benefit to the subject, but low enough to avoid adverse effects, such as toxicity, irritation, or allergic response, commensurate with a reasonable benefit / risk ratio when used in the manner of this disclosure. Such an effective amount is readily determined by one of ordinary skill in the art, and will vary with e.g. the particular health component used, the particular condition being treated, the age and general health condition of the subject, the duration of the treatment, the nature of any accompanying therapy (if any), the particular dosage form used, the carrier employed, the solubility of the dosage form, and the particular dosing regimen chosen.

[0035] The terms "health component", "functional component", "health ingredient" and "functional ingredient" as used in the present application are used interchangeably in the present application and refer to components or ingredients that promote health and well-being, prevent disease or enhance well-being, including pharmaceutical products such as antibiotics designed to treat or prevent infectious diseases, antiseptics and topical disinfectants, antioxidants, phytochemicals, hormones, vitamins such as vitamins A, Bl, B2, B6, B 12, C, D, E, K, pantothenic acid, folic acid, provitamins, minerals such as calcium, selenium, magnesium salts, available iron and iron salts, microorganisms such as bacteria, e.g. live lactobacilli, fungi and yeasts, 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 amylases, proteases, lipases, pectinases, cellulases, hemicellulases, pentosanases, xylanases and phytases, pigments, oligopeptides, dipeptides and amino acids, and mixtures thereof.

[0036] The term "prebiotic" as used in the present application means "non-digestible food ingredients that beneficially affect the host by selectively stimulating the growth and / or activity of one or a limited number of bacteria in the colon, which can improve the host's health", for example, 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 can be naturally occurring, synthetic or developed through genetic manipulation of organisms and / or plants, whether such new sources are now known or later developed. Prebiotics useful in the present disclosure can include oligosaccharides, polysaccharides and other prebiotics containing fructose, xylose, soy, galactose, glucose and mannose, for example, in Ramirez-Farias et al., Br J Nutr (2008) 4: 1-10; Pool-Zobel and Sauer, J Nutr (2007), 137: 2580S-2584S. More specifically, prebiotics useful in the present disclosure can include lactulose, oligosaccharide sucrose, raffinose, glucose oligodextrin, inulin, polydextrose, polydextrose powder, fructooligosaccharide, isomalto-oligosaccharide, soy oligosaccharide, lactosucrose, xylooligosaccharide, chitooligosaccharide, oligomannan or mannose oligosaccharide (MOS), arabino-oligosaccharide, sialyl-oligosaccharide, fucosyl-oligosaccharide, galacto-oligosaccharide and gentio-oligosaccharide. In addition, prebiotics useful in the present disclosure include molecules such as beta-methyl-d-galactoside and N-acetyl-d-mannosamine, for example, in Slomka et al., J Clin Periodontol. (2017), 44(4):344-352. In one embodiment, the daily dose of prebiotics is from about 0.00001 g to about 1 g, more preferably from about 0.0001 g to about 0.5 g, even more preferably from about 0.0005 g to about 0.1 g of prebiotics.

[0037] The term "probiotic" as used in the present application refers to live, dead and inactivated microorganisms that confer a health or wellness benefit to the host when administered in sufficient amounts. Examples of such probiotics include substantially pure bacteria (i.e., single isolates) or mixtures of desired bacteria. Health benefits can include those related to cardiovascular health, bone health, gut health, oral health, skin or dermal health, anti-stress or behavioral health, and immune health. For the purposes of the present disclosure, "probiotic" is further intended to include active metabolites produced by the microorganisms of the present invention if they are not shown separately. Such cellular metabolites can be obtained by using lysates or fermentation supernatants of the probiotics. Metabolites can include organic and inorganic molecules, alcohols, aldehydes, amino acids, carbohydrates and components thereof, peptides, proteins and components thereof, extracellular enzymes, cell wall-bound enzymes, membrane-bound or intracellular enzymes, electron transport molecules and components thereof, or other cell wall, membrane or cytoplasmic components and molecules, hormones or hormone-like substances, lipids, oils, fats or fatty acids and components thereof, organic acids, nucleic acids or ribonucleic acids and components thereof, carbon compounds, nitrogen compounds, phosphorus compounds, pigments and vitamins, as well as mixtures of any of the above components and molecules, e.g., in Fernandez-Gutierrez et al. (2017) Scientific Reports | 7: 11100 | DOI: 10.1038 / s41598-017-11446-z, and e.g., in MacKenzie et al., Microbiology (2010), 156, 3368-3378. For the purposes of the present disclosure, "probiotic" is further intended to include inactivated or dead probiotics and yeasts, such as those used for co-aggregation of specific microorganisms or other prokaryotic or eukaryotic cells and components thereof.

[0038] Examples of microorganisms recognized as probiotics are Acetobacterium, Acetitomaculum, Bacillus, Bergeyella, Bacteroides, Blautia, Bifidobacterium, 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, and mixtures thereof.More specifically, 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 or Streptococcus thermophilus.

[0039] Enzymes and proteins can also be used as health ingredients, such as amyloglucosidase, glucose oxidase or glucosidase, lactoperoxidase, mutanase, dextranase, lipase, laccase, peptidase or protease, xylanase, other polysaccharide-degrading enzymes and other hydrolytic enzymes; proteins such as colostrum (lactoferrin, sIgA), bacteriocins, lytic phage or components thereof, proteins or other inhibitors of cell density sensing in target bacteria and other microorganisms. Lipids and their derivatives such as polyunsaturated fatty acids or omega-3 fatty acids, monounsaturated fatty acids such as 1-tetradecanol complex (e.g. Hasturk et al., 2007, J Periodontology, vol. 78: 924-932) and fatty acid derivatives such as those described in WO 2011 / 061237 can be dispensed to the oral cavity of companion animals. These publications and / or patent applications in the present specification are incorporated by reference and relied upon in their entirety.

[0040] The term "pharmaceutically acceptable" or "veterinarily acceptable" as used in the present application refers to molecular entities and compositions that do not produce an adverse, allergic or other untoward reaction when administered to an animal. Moreover, for animal administration, it will be appreciated that preparations should meet sterility, pyrogenicity, general safety and purity standards as required by the FDA, USDA or European Drug

[0041] The term "palatability agent," "palatability enhancer," "flavoring agent," "flavor," or "flavor enhancer" means any material or substance that enhances the palatability of a food composition to an animal. The palatability agent or palatability enhancer can be a single material or a mixture of materials, and can be a natural (unprocessed or processed), synthetic, or partially natural and partially synthetic material. The palatability agent can be added to the composition as an additive, which includes the palatability agent or includes the palatability agent and one or more other functional or nonfunctional substances. The palatability enhancer can be made in whole or in part from meat or poultry broth concentrates or spray dried powders, hydrolyzed proteins, yeast and / or yeast extract, liver, flavoring spices, herbs, sweeteners, or any combination of such components.

[0042] The terms "treating," "treatment," or "to treat" as used in the present application means reversing, alleviating, or inhibiting the progress of a disease, disorder, or condition; or reducing or eliminating the likelihood or incidence of a disease or disorder in a subject as compared to an untreated control population, or as compared to the same subject prior to treatment; or delaying or preventing symptoms associated with a disease, disorder, or condition. As used in the present application, "treatment" can also mean preventing the recurrence of a disease, disorder, or condition or one or more symptoms associated with such a disease, disorder, or condition.

[0043] Delivery system

[0044] The delivery system according to the present disclosure comprises an ingestible matrix, one or more functional ingredients substantially uniformly and completely dispersed in the ingestible matrix, and wherein the use of a whipped egg white foam as a delivery vehicle greatly facilitates solubility and release characteristics in the delivery of any functional ingredient.

[0045] Egg white is a transparent viscous dispersion of biologically active proteins in the aqueous medium surrounding the yolk of an avian egg. The egg white of a domestic chicken egg is about 10% mixed proteins, including ovalbumin, ovotransferrin, immunoglobulin, lysozyme, and avidin, among others. Egg white can be separated from the yolk by mechanical means and is commonly used in foods as a source of protein and as an adhesive and thickener in processed meats. By whipping and beating in a manner that induces molecular shear, the egg white can be transformed into a foam, which forces normally coiled protein molecules into a linear conformation, creating a tenacious interface with entrapped air bubbles. In other food applications, egg white foam is used to make various confections, including marshmallows and nougat, in which boiling sugar syrup is blended with whipped egg white, baked to solidify and set, and entrapped air bubbles, creating a light, multi-foamed material upon cooling.

[0046] The process of whipping (or beating) egg white proceeds through several stages of firmness, commonly described as "soft," "firm," and "stiff" peaks, after which the foam will collapse if whipping is continued. The volume of whipped egg white is typically about 4 times greater than the original liquid egg white, and the entrapped air bubbles are typically microscopically dispersed, with occasional large visible air bubbles. Soft and firm peak foams can be easily blended with other solutions or solid dispersions in aqueous media, and when so done, they serve to disperse the entrapped air throughout the combined mass. Stiff peak foams are less easily dispersed, tending to break up into uneven clumps, but they can be baked solidified by gentle heating, after which they form light and airy honeycombed clumps, meringue frosting being a good example thereof.

[0047] While egg white foams are popular and commonly used for baked solidification purposes, their use in delivering biofunctional ingredients, such as nutrients and drugs, is novel, and as disclosed in this application, egg white foams contribute to the constructs of the present invention that provide great utility to specific classes of functional ingredients designed for therapeutic and nutritional applications.

[0048] As disclosed in this application, it is possible to formulate functional ingredients using whipped egg white foams in a manner that concentrates the functional ingredients at the foam-air interface, i.e., on the surface within individual air bubbles. Egg white foams with surface concentrated functional ingredients provide greater available dose load, which can be released much more rapidly than conventional topical formulations.

[0049] Among the different classes of functional ingredients, many are water soluble, some are only soluble in oil, while a few are amphiphilic, exhibiting partial solubility in both oil and water in a surfactant-like manner. The solubility of any functional ingredient greatly influences the appropriate manner of its delivery to the human or animal body, particularly in oral applications, where the functional ingredient is envisioned to affect reactions on or in the gastrointestinal tract, and topical and mucosal applications, where the functional ingredient is envisioned to affect reactions on or in the skin or mucosa, and by extension, structures emanating from these surfaces, such as hair, nails, and teeth.

[0050] Generally, functional ingredients, including drugs and nutrients, that are freely soluble in water present little impediment to incorporation into any formulation. However, achieving sufficient release from the formulation is not always easy, as water-soluble ingredients will be freely dispersed throughout the administered dose, making absorption or assimilation of the entire carrier essential to access the functional ingredient. The use of whipped egg white foams can be used to facilitate the separation and free concentration of water-soluble ingredients to enhance delivery, where the water-soluble ingredients are dispersed and immobilized at the foam interface with a significantly enlarged surface area, which provides an amplified available dose when the foam itself is dispersed in other carriers.

[0051] Formulations of poorly soluble functional ingredients typically contain excipients designed to promote solubility, absorption, and / or residence time on the intended surface. The available dose of any functional ingredient in such formulations is also limited by the amount of formulation that can be applied to the intended surface and the migration or release of the functional ingredient from the formulation onto or into the intended surface. Solubility and release characteristics are key parameters for the delivery of any functional ingredient, and as disclosed in this application, the use of whipped egg white foam as a delivery vehicle can significantly facilitate both.

[0052] Oils and oil-soluble ingredients, as well as many amphiphilic substances, present more challenging problems in formulation. It is well known in the field of bakery solidification that any trace of oil or fat will prevent the whipping of egg white, and likewise, once egg white is whipped and foamed, the addition of trace amounts of fat or oil or oil-soluble ingredients will cause the foam to collapse. Egg white foam is generally incompatible with any lipophilic (fat-soluble) ingredients, and this presents a technical challenge in the use of such foams to enhance the delivery of oil-soluble or amphiphilic functional ingredients.

[0053] The use of emulsification techniques to disperse fine droplets of oil-based ingredients, particularly if such droplets are stabilized by amphiphilic excipients, facilitates more flexible incorporation and release characteristics from whipped egg white foam.

[0054] Emulsions are dispersions of oil droplets in aqueous media (oil-in-water type) in which an emulsifier is used to prevent coalescence of the oil droplets. An example of a functional emulsion is provided by Folan in U.S. Patent Application Serial No. 15 / 384,372, based on WO 2011 061237, which is incorporated in its entirety into this application. In that application, water-insoluble free fatty acids (oil) are emulsified in membrane lipids of natural origin, the free fatty acid is preferably caprylic acid, and the emulsifier is preferably delipidated lecithin.

[0055] Surface area is a key parameter influencing the release characteristics and delivery of any functional ingredient. The example of a cream on the skin is used to illustrate the critical nature of surface area. The contact surface of the cream on the skin is the delivery interface, and the available dose of the functional ingredient is the amount of functional ingredient at the contact surface. The addition of further layers of cream does not immediately increase the available dose, as the functional ingredient must first migrate through the additional layers before it is available at the skin interface. The use of egg white foam as a delivery vehicle greatly expands the available surface, with the result that the release characteristics are improved.

[0056] In the case of delivering functional ingredients, it should be recognized that the total surface area of an individual foam will vary depending on the degree of whipping and the actual protein concentration of the starting solution. For the purposes of this disclosure, it is sufficient to know that a whipped egg white foam with approximately four times the volume will provide approximately several hundred times more surface area than the original protein solution or any equivalent volume of non-foamed formulation.

[0057] As disclosed herein, the functional ingredient can be formulated in a manner that uses whipped egg white foam to concentrate the functional ingredient at the foam-air interface (i.e., on the surface within the individual bubbles). Egg white foam with surface concentrated functional ingredient provides a greater available dose load than conventional topical formulations, which can be released much more quickly.

[0058] Delivery systems according to the present disclosure are suitable for administration to both humans and non-human animals. Those skilled in the art will appreciate that each delivery system can be formulated differently depending on the type of animal to which it is administered. For example, for administration to animals such as cats or dogs, meat or fish based flavors and odorants can be added. For administration to humans, the delivery system can be formulated as a confectionery, for example, using fruit based or other flavors. Delivery systems are particularly suitable for oral administration due to their palatability. Additionally, due to the highly portable form, delivery system administration and consumption is simple and convenient for both humans and other animals.

[0059] Delivery systems of the present disclosure can be tailored for specific purposes; thus, the delivery system can be formulated with a specific combination of functional ingredients to produce a particular physiological effect. For example, a pharmaceutical delivery system can be formulated to contain certain combinations of pharmaceutical or diagnostic agents. Other delivery systems can be formulated with combinations of functional ingredients, for example, to promote endurance, promote cardiovascular health, control fat and / or cholesterol, promote healthy joints, maintain or improve bone density, enhance cellular antioxidant capacity, or control appetite.

[0060] Delivery systems of the present disclosure comprise one or more functional ingredients substantially uniformly dispersed within a matrix, generally the matrix comprises 1) egg white at a protein concentration that forms a foamed matrix upon whipping; 2) one or more heat resistant and / or heat sensitive gelling agents; 3) a pH adjusting agent; 4) one or more plasticizers and / or humectants; 5) one or more sources of water. The inclusion of one or more gelling agents facilitates the water content within the matrix and controls the physical properties of the residual moisture. Additives such as natural or artificial flavorings, colorings, acidulants, buffers, and sweeteners can be included in the matrix in conventional amounts.

[0061] The delivery system of the present disclosure can be formulated such that the final pH of the matrix is in the range of about 2.5 to about 8.5. In one embodiment, the final pH of the matrix is about 3.0 to about 8.5. It is known in the art that acidic pH promotes the degradation of certain functional ingredients. Thus, for the formulation of a delivery system that delivers a functional ingredient that is sensitive to or reacts at acidic pH, the final pH of the matrix is neutral to slightly basic. Neutral to slightly basic pH means that the final pH is about 6.0 to about 8.5. For those functional ingredients that are more stable in acidic form, such as trimethylglycine, or that can react with other ingredients at neutral pH, such as glucosamine hydrochloride, the pH of the matrix of the delivery system can have a final pH that is less than neutral.

[0062] In one embodiment of the present disclosure, the delivery system is formulated such that the matrix has a final pH of about 5, thus being suitable for the delivery of functional ingredients that are stable and / or unreactive at acidic pH.

[0063] As described in the examples below, formulations containing foam egg white typically include other water-soluble ingredients, such as gels, polymers, and organic acids, which, when baked solidified with the egg white proteins, constitute the solid skeletal structure of the foam into which the gas bubbles are infused. When oil-based ingredients or oil-in-water emulsions are added to the solid matrix, there is a phase repulsion between the aqueous medium and the oil droplets, resulting in the migration of these droplets to the location where the resistance is the least, which is the water-air interface within the trapped gas bubbles.

[0064] Due to the vastly expanded surface area and the concentration of oil droplets at the surface of the foam gas bubbles, a formulation incorporating emulsified oil will have a much greater available dose load and a much faster release profile compared to a non-foamed formulation of similar mass.

[0065] The texture, physical properties, form, and shape of the matrix, as described below, can be altered by varying the proportions of the ingredients within a given range using the methods described in this application or by methods well known to those skilled in the art. Furthermore, the specific selection of possible ingredients provided below must be safe for consumption by animals and / or humans and meet regulatory standards, such as those of the Codex Alimentarius.

[0066] Egg white foam formulations that deliver functionally active emulsions are envisioned to have great utility in topical skin and mucosal healthcare, where rapid release of the available dose load is desirable due to, for example, short transit times over the oral mucosa. Exemplary emulsions include (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 delipidated membrane lipids as emulsifiers for the free fatty acid or salt thereof.

[0067] The same type of improved formulation can be used to protect emulsion droplets using whipped egg white as a protein coating to delay gastric digestion and achieve enhanced intestinal availability and absorption of functional ingredients carried in emulsified oil. Protein digestion in the mammalian stomach is primarily due to pepsin activity at low pH. Some individual proteins in egg white, particularly ovalbumin and ovomucoid, are particularly resistant to pepsin digestion, the addition of lecithin to egg white increases resistance to pepsin, and whipping prior to baking solidification aids in intact gastric transit. Once in the duodenum, trypsin proteolysis can affect the rapid release of encapsulated oil emulsions and their availability for absorption at the intestinal cells.

[0068] Emulsions of the above type are not limited to the use of free fatty acids. Emulsification technology can be used to deliver oil-soluble ingredients themselves or their solutions in other oils, such as neutral triglycerides, of which Miglyol 812N from IOI Oleo, Hamburg, Germany is one example. The same oil-water phase repulsion will be applied to concentrate the oil droplets at the water-air interface inside the bubble, regardless of the type of oil in the emulsion droplet and regardless of any oil-soluble ingredients in the oil. Examples of other oil-soluble functional ingredients that would benefit from enhanced delivery in emulsions dispersed in whipped egg white foam include, but are not limited to, antibiotics, such as mupirocin, antifungals, such as clotrimazole, antiseptics, such as chlorhexidine, anti-inflammatories, such as ketoprofen, and nutraceuticals, such as oil-soluble vitamins A, D, E, and K.

[0069] Whipped egg white foam is particularly useful for incorporating and delivering functional ingredients that exhibit amphiphilic properties, including local anesthetics, such as lidocaine, biocides, such as benzalkonium chloride, antimicrobials, such as delmopinol, and anti-inflammatories, such as curcumin. When dispersed in egg white before or after foaming, the hydrophilic aspect of the amphiphilic molecule will tend to bind with the water-based protein matrix, while the lipophilic aspect (also known as hydrophobic) will naturally orient at the water-air interface and / or with the lipophilic aspect of adjacent molecules, facilitating the establishment of micelles and lamellar structures, all of which can be used to design improved release characteristics.

[0070] In embodiments, lecithin is used in combination with whipped egg white foam. Lecithin is an amphiphilic molecule that can be extracted from plant sources, such as soybean and egg yolk, where it is intimately bound with egg white, but distinctly separate. As demonstrated in this application, lecithin can be combined with egg white prior to whipping, where despite its amphiphilic nature, it has little effect on the foaming properties of the egg white, but from there it greatly facilitates the inclusion and release of other amphiphilic and lipophilic substances as described previously, including but not limited to delmopinol, curcumin, lidocaine, and benzalkonium chloride.

[0071] In other embodiments, lecithin is used in combination with whipped egg white to facilitate the in situ construction of a free fatty acid emulsion as part of the formulation process. While foamed egg white is incompatible with oil and will collapse even if trace amounts are added, a method has been developed to combine specific oils, such as free fatty acids in the form of water soluble sodium or potassium salts, with egg white prior to whipping without significantly affecting the foaming properties, by adding an appropriate amount of emulsifier such as de- fatting lecithin to the egg white. After the foam has been incorporated into the finished formulation, the salt of the free fatty acid can be converted back to its protonated oil form by acidification without affecting the foaming properties.

[0072] De-fatted lecithin is amphiphilic and exhibits superior emulsification properties due to one face being oil soluble and the opposite face of the same molecule being water soluble. De-fatted lecithin can be added to an egg white solution and, if allowed to hydrate for an appropriate time, it disperses uniformly throughout the solution.

[0073] In embodiments, a water soluble salt of octanoic acid such as sodium octanoate (sodium octanoate) can also be added in appropriate proportions with the de-fatted lecithin. The egg white / de-fatted lecithin / sodium octanoate mixture can be whipped and the texture of the blended foam is more viscous due to the added ingredients, but the degree of air incorporation is about the same. Typically, the blended egg white foam is added to a gel formulation and baked solid in the gel formulation, after which an amount of organic acid such as citric acid or ascorbic acid is added to the formulation in molar equivalent amounts relative to the amount of sodium octanoate. The effect of acidification is to lower the pH below the dissociation constant (pKa) of sodium octanoate, at which point the salt converts to its water insoluble free fatty acid oil. The sodium octanoate is intimately dispersed in the egg white with the de-fatted lecithin prior to whipping and remains intimately dispersed during and after whipping and during foam incorporation and bake solidification in the gel formulation. When the formulation is acidified to below an appropriate pH, the intimately dispersed sodium octanoate converts to its free acid oil and binds with the lipophilic face of the co-dispersed lecithin by attraction, in a form similar to an emulsified oil droplet, at or at least very near the air interface of the whipped egg white foam.

[0074] It will be appreciated that any functional ingredient that does not interfere with the whipping and foaming of egg white can be incorporated directly into the whipping process. And further, incorporation at the foam air interface will enhance the delivery of any compatible ingredient due to the amplified available dose and improved release properties at the expanded surface area of the foam.

[0075] The foam egg white matrix can optionally comprise other additives that do not interfere with the whipping and foaming of the egg white, such as sweeteners, chelating agents, flavoring agents, coloring agents, modified plant gums or celluloses, or combinations thereof. It will be very apparent that the additives included in the matrix should be selected so that they do not affect the properties of the matrix, do not exhibit substantial reactivity with the functional ingredients in the matrix, and are stable during the preparation of the matrix.

[0076] Sweeteners can be selected from a wide variety of suitable materials known in the art. Representative, but non-limiting examples of sweeteners include sugars, including but not limited to sucrose, fructose, lactose, sorbose, and glucose, and alcohol derivatives of sugars, including but not limited to glycerol, xylitol, sorbitol, larchitol, and erythritol, as plasticizers, further imparting utility in the construction of whipped egg white formulations, with or without additional gelling agents. The ratio of egg white to selected sugar and / or sugar derivative can range from 1.0:0.1 to 2.0:10.0 or 1.0:5.0 to 1:1.

[0077] Metal salts and free metal ions such as magnesium, calcium, zinc, and iron are generally problematic and can inhibit reactive functional ingredients, 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 whipping and or to other ingredients in the gel matrix. Suitable chelating agents include, but are not limited to, orthophosphates and polyphosphates, such as disodium orthophosphate or dipotassium orthophosphate, uridine diphosphate disodium, sodium myo-inositol hexaphosphate, and sodium hexametaphosphate. Non-phosphate based chelating agents include trisodium citrate and ethylenediaminetetraacetic acid. Chelating agents can be incorporated at 0.1% W / V to 5.0% W / V.

[0078] Some chelating agents inhibit microbial growth by sequestering essential mineral metabolites, particularly in environments where these metabolites are available at very low concentrations. Generally, microbial growth is restored when the mineral supply is supplemented, although, as exemplified in this application, it was surprisingly found that, in certain embodiments, emulsions comprising other functional ingredients such as free fatty acids will synergize with chelating agents to inhibit microbial growth in the presence of excess mineral supplementation.

[0079] It will be understood by those skilled in the art that certain physiological environments have characteristically higher mineral concentrations, these include blood, serum, mucus, and / or saliva, where divalent metal ions are essential. In the treatment of, for example, wounds, it can be desirable to reduce the concentration of divalent ions such as calcium to inhibit clotting, and where a microbiocidal effect is also desired, the combination of a chelating agent such as hexametaphosphate with a functional emulsion of free fatty acids can impart great utility.

[0080] It is also well known that saliva is supersaturated with respect to calcium ions, and in addition, the non-selective deposition of calcium in dental plaque leads to the stubborn accumulation of calculus, which greatly exacerbates the risk of gum disease. In formulations intended to promote oral health and / or treat or prevent oral disease, the use of a calcium sequestering agent to reduce calculus can be advantageous. If an antimicrobial effect is desired to limit plaque formation, the synergistic combination of hexametaphosphate and a functional emulsion of free fatty acids achieves significantly enhanced health benefits.

[0081] Sequestering agents such as polyphosphates are commonly used in skin care formulations to stabilize and prevent degradation reactions that are typically catalyzed by divalent metal ions. In medicated cosmetic applications, for example, where an additional antimicrobial effect is desired, the synergistic combination of polyphosphate and a functional emulsion of free fatty acids is particularly beneficial. One example of such a medicated cosmetic is a skin cream for acne, another example is a shampoo designed to improve infected dandruff.

[0082] Suitable flavoring agents that can be added to the delivery system include synthetic flavor oils and flavoring agents derived from various sources, such as fruits, leaves, herbs, flowers, fruits, nuts, etc. Representative flavoring oils include spearmint oil, peppermint oil, cinnamon oil, and oil of wintergreen (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, and fruit essences including apple, strawberry, cherry, pineapple, banana, raspberry, and combinations thereof.

[0083] The amount of flavoring agent used is generally dictated by the concentration / dilution of the flavor stock, the flavor type, the substrate type, and the desired intensity. Generally, amounts of about 0.01% to about 5.0% by weight of the final product are useful.

[0084] In one embodiment of the present disclosure, vanillin is included as a flavoring agent in the substrate in an amount of about 1.5%. In another embodiment, the flavoring agent is added in an amount of about 0.03% to about 1.5%.

[0085] Colorants suitable for use in food products can optionally be included in the substrate to increase aesthetic appeal. Various suitable food colorants are commercially available from, for example, Warner Jenkins, St. Louis, Mo. If synthetic colorants are used in the substrate, they are included in an amount of about 0.01% to about 2% by weight.

[0086] In one embodiment of the present disclosure, a synthetic colorant is added to the substrate in an amount of about 0.03% to about 1% by weight.

[0087] Because the functional ingredient is substantially uniformly and completely dispersed within the matrix, the delivery system is suitable for division into subunits. For example, if a single unit of the delivery system of the present disclosure is divided into three subunits, each subunit contains one-third of the original unit dose. This splitting is not possible for other delivery systems in which the functional ingredient is not uniformly dispersed.

[0088] In embodiments, the foamed egg white matrix is used as part of a dual action chew for dogs. This dual action chew works like a toothbrush and toothpaste to keep the dog's oral cavity clean and prevent harmful bacteria. The chew comprises two components; a flexible matrix and a filler. The flexible matrix is shaped and designed to reduce plaque and calculus through mechanical action (scouring, abrasion) during mastication. In addition, the chew matrix is characterized by a "depot" / cavity for a filler, which comprises a functional ingredient. The filler comprises a foamed egg white matrix and at least one functional ingredient, and wherein the filler and the functional ingredient are distributed in the oral cavity during mastication, which provides a mechanical barrier that prevents bacteria from adhering to surfaces in the oral cavity (teeth, tongue, and gums).

[0089] In embodiments, the chew matrix is bone-like and has ridges and nodules on at least a portion of the exposed surface area to enhance mechanical cleaning.

[0090] In embodiments, the functional ingredient in the filler comprises an 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 delipidated membrane lipids as an emulsifying agent for the free fatty acid or salt thereof.

[0091] Materials and methods

[0092] The construction of the whipped egg white foam, with or without incorporation of a functional ingredient such as a free fatty acid salt and / or lecithin, is based on an aqueous dispersion of ovalbumin.

[0093] The use of fresh egg white is not particularly suitable for an industrial scale process, and commercially available powdered egg white provides greater convenience as well as the opportunity to vary the protein concentration in the foam. Egg white powder is available from a number of sources, including Canadian Inovatech, Abbotsford, BC, Canada.

[0094] Egg white powder is rehydrated in water that has been purified by reverse osmosis. A 10% W / W dispersion of ovalbumin is 10 grams of powdered egg white in 90 grams of water. Depending on the type of foam desired and the amount of other ingredients incorporated, dispersions of up to 40% protein can be rehydrated. Higher protein concentrations do not yield the same volume during whipping, but they are suitable for other foaming methods, including the use of hydrogen peroxide and catalase.

[0095] Whipping and foam formation of egg white comprises a protein skeleton that traps a large amount of air, which needs to be immobilized by heating to about 80°C to denature the skeleton and make it insoluble. The water content facilitates heat transfer to the protein skeleton and the physical properties that control residual moisture are facilitated by including other gelling agents (hydrocolloids). Hydrocolloids are hydrophilic polymers of vegetable, animal, microbial or synthetic origin, which are naturally present or added to aqueous food products for various reasons due to their unique textural, structural and functional properties. Typically, they are used because of their thickening, gelling properties and / or heat resistance and their water binding and sensory properties. Hydrocolloids can also be used to improve and / or stabilize the texture of a food product while inhibiting crystallization. Examples of hydrocolloids include, but are not limited to, starch, gum tragacanth, gluten, fumed silica, polyethylene glycol, cellulose and cellulose derivatives, gelatin, collagen, mucin, pectin, gum arabic, guar gum, gum arabic, karaya gum, locust bean gum, xanthan gum, carrageenan, agar, gellan gum and / or sodium alginate and combinations of these.

[0096] The choice of hydrocolloid used in the matrix will depend on the pH of the matrix and the texture and consistency required of the final product. The type of hydrocolloid used also affects the setting temperature of the matrix. For example, the use of a gelatin / gellan gum mixture or a gelatin / pectin mixture provides a setting temperature of about 35°C, while the use of carrageenan or locust bean gum results in a setting temperature closer to 60°C, and the use of agar will result in a setting temperature closer to 45°C. Thus, the choice of hydrocolloid for use in the matrix also depends on the nature of the functional ingredient to be incorporated into the delivery system. Functional ingredients that are not stable at higher temperatures require the selection of a hydrocolloid or mixture of hydrocolloids with a low setting temperature, while more stable functional ingredients can be used with hydrocolloids with higher setting temperatures.

[0097] In one embodiment of the disclosure, the matrix comprises gelatin. The term "gelatin" refers to an inhomogeneous mixture of high average molecular weight, water-soluble proteins derived from collagen-containing portions of animals (e.g., skin, bone, and bone collagen) by hydrolysis, usually acid or alkali hydrolysis. Different types of gelatin can be prepared by varying the process parameters. Gelatin is often defined using the "Bloom value," which represents the strength of a gel formed using the gelatin under certain conditions. In the preparation of confections, when a harder gel is desired, gelatin with a higher Bloom value is used. Conversely, when a more flowable final product is required, gelatin with a lower Bloom value is used. The water capacity of gelatin alone is lower than the water capacity of a combination of gelatin with another hydrocolloid (e.g., gellan gum or pectin), and can necessitate the use of a higher amount of gelatin to achieve the desired gelation / texture of the matrix. When the hydrocolloid in the matrix of the disclosure comprises gelatin, the Bloom value (BL) is typically about 100 to 300 BL.

[0098] In one embodiment, the Bloom value is about 260 BL. In another embodiment, a mixture of gelatins with different Bloom values is used.

[0099] As shown above, gelatin can be combined with one or more other hydrocolloids to impart slightly different properties to the matrix. For example, gelatin with agar, gelatin with pectin, or a combination of gelatin with agar and pectin provide good texture to the matrix. Other combinations of hydrocolloids are also contemplated, such as, but not limited to, agar with pectin. When a combination of gelatin and agar is used in the preparation of the matrix, the gelatin:agar ratio is typically in the range of about 1 : 1 to about 10: 1. These relative amounts provide a cohesive structure to the delivery system.

[0100] In one embodiment of the disclosure, a combination of gelatin and agar is used to prepare the matrix at a gelatin:agar ratio of about 1 : 1 to about 3: 1.

[0101] In embodiments, the total amount of hydrocolloid incorporated into the matrix is typically about 0.1% to about 7.0% by weight. In one embodiment, the total amount of hydrocolloid in the matrix is about 0.5% to about 6.8% by weight. In another embodiment, the total amount is between about 1.0% and about 6.0%. In other embodiments, it is about 2.0% to about 6.0%, about 4.0% to about 6.0%, about 5.0% to about 6.0%, and about 6.0% to about 7.0%.

[0102] In embodiments, the ratio of whipped egg white to selected gelling agent can be in the range of 2: 1 to 0.2: 10 or 0.1 : 1 to 1 : 1.

[0103] In other embodiments, the ratio of egg white to gelling agent can be in the range of 0.01 : 10 to 1.0: 10 or 1.0: 10 to 10: 1.

[0104] Gelatin suitable grade is 260 bloom 40 mesh purchased from PB Leiner, Belgium and food grade agar and other gelling agents are available from many sources including Special Ingredients Ltd, Chesterfield, UK.

[0105] The effect of the gelling agent on the release characteristics and physical stability of the finished formulation in actual use must be considered.

[0106] In embodiments, other ingredients used in the formulation incorporated into the whipped egg white matrix include caprylic acid or sodium caprylate, which are available from Merck Chemicals.

[0107] In embodiments, the ratio of caprylic acid to egg white can be in the range of 0.01 : 10.0 to 1.0: 10 or 0.1 : 1.0 to 1.0: 1.0.

[0108] In embodiments, other ingredients used in the formulation incorporated into the whipped egg white matrix include lecithin.

[0109] Suitable grade of purified lecithin is available from Lipoid AG, Zurich, Switzerland. In embodiments, the ratio of lecithin to egg white can be in the range of 0.01 : 10.0 to 1.0: 10 or 0.1 : 1.0 to 1.0: 1.0.

[0110] Determination of functional efficacy

[0111] It will be appreciated that the disclosure herein relates to the delivery of a wide range of functional ingredients that provide enhanced utility in human and animal health care, including but not limited to therapeutic agents, prophylactic agents and nutraceuticals.

[0112] To illustrate the use of a whipped egg white based formulation, the following example utilizes the antimicrobial emulsion disclosed in Folan U.S. Patent Application 15 / 384,372. This functional ingredient exerts a dual antimicrobial effect by limiting the adhesion of microbial species and reducing their viability through a secondary microbicidal / sub microbial action. For comparative purposes, an assay for microbicidal / sub microbial action is used here and is described as follows.

[0113] This 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 weight of test material, blank or control. After a set time period, a neutralizing solution is added to terminate the antimicrobial action and the residual viable microbial population is enumerated by serial dilution and plating. The enumeration method is a standard and fundamental microbiological method for counting viable microorganisms and is well known to those skilled in the art.

[0114] In its general form, the method requires 1 gram or 1 ml of test sample to be inoculated with 0.1 ml of 18 hour (late log phase) bacterial culture, followed by vigorous agitation to mix. After the predetermined exposure time has elapsed, 9.0 ml of neutralisation buffer is added and mixed. This has the effect of terminating the microbicidal action, which allows the percentage kill achieved by the test sample over the time period between inoculation and neutralisation to be reliably estimated. Typically, the exposure time period will be in the range 30 seconds to 30 minutes, and can progress to several hours if that time period is required to measure the effect. To count the surviving viable cells and hence calculate the percentage kill, the number of viable cells in the inoculum is determined by serial dilution and plating. Appropriate blanks and controls are used to ensure the effectiveness of the neutralisation process and to allow for any interference from other components in the test sample.

[0115] In the assays described in this application, the test organism is the standard indicator bacterium, Staphylococcus aureus NCTC 8325-4 (National Collection of Type Cultures, Public Health England, Porton Down, Salisbury, UK), known for its tenacious biofilm-forming ability. Bacterial stocks are typically stored at -80°C on beads in 50% glycerol. When viability / microbicidal assays are required, small aliquots from these stocks are streaked onto appropriate nutrient agar, grown and subcultured to ensure purity. Where broth cultures are required, 250 ml conical flasks containing 100 ml broth are inoculated with a transfer loop from a pure agar culture and incubated at 37°C in a constant agitation incubator.

[0116] The indicator bacteria are routinely cultured using Brain Heart Infusion (BHI) broth and agar or Tryptone Soya Broth or Agar (TSB), both of which are commercially available from Oxoid, UK. The dilution and neutralisation buffer used in this method is Phosphate Buffered Saline (PBS), containing 137 mM sodium chloride, 2.7 mM potassium chloride and 10 mM phosphate, to which is added 3% polysorbate Tween 80 (an anionic surfactant), 0.3% lecithin and 0.5% histidine as neutralising agents. These “neutralising” agents are those specified under the ISO accredited EU guidelines for microbicidal efficacy, and are validated to neutralise free fatty acids at the concentrations used in this application.

[0117] Test samples prepared in the following examples were assayed by first dissolving or dispersing a measured amount of sample in a measured amount of sterile water. Typically, 1 gram of sample was macerated with 1 gram of water, representing a 50% dilution of the sample and its effective dose load. The macerated sample was inoculated with 1 ml of an 18 hour (late log phase) indicator organism culture, agitated and incubated for a fixed period of time at 37°C, after which 9 ml of neutralization buffer was added and mixed by inversion. The number of viable cells in the test sample after incubation and neutralization was measured by serial dilution and plating, and compared to the number of viable cells in a 1.0 mL control inoculum treated in exactly the same manner as the test sample or with a blank test sample containing no functional ingredient.

[0118] Typically, overnight cultures of the indicator organisms contain more than 8 log of viable cells per milliliter (1.0 X 10 8 Or 100,000,000) per ml. Typically, a 2% W / W dose load of the free fatty acid emulsion used in the following examples will achieve greater than 90% viability or a 1 log reduction within 30 seconds of exposure, and it is not uncommon to observe greater than 6 log (99.9999%) reduction within 5 minutes. Example

[0119] These delivery systems and methods of making the delivery systems are exemplary only, other formulations and methods will be apparent to those of ordinary skill in the art, and such other formulations and methods are contemplated to be within the scope of the present invention.

[0120] Example 1 - Egg white / gelatin / sorbitol formulation using an oil-in-water emulsion as the functional ingredient

[0121] Table 1: Foam egg white base formulation of Example 1

[0122]

[0123]

[0124] A foam egg white base containing a functional emulsion was prepared according to the following method;

[0125] (a) At room temperature, combine ingredients 1 (purified water), 2 (citric acid), 3 (egg white) and 4 (gelatin) from Table 1 in the amounts indicated in a suitable container and allow approximately 30 minutes for the gelatin to fully hydrate,

[0126] (b) Using a suitable grade of equipment with a whipping attachment, whip / beat the mass carefully for approximately 5 minutes to obtain a foam mass that holds its shape - a firm peak when pulled upward,

[0127] (c) The material is heated (using a water bath or Bain Marie) while constantly stirring and using a suitable thermocouple in the foam and bringing the material to about 80°C,

[0128] (d) Ingredient 5 (sorbitol) is added in the amounts shown in Table 1 and stirred. The foam material cools to about 60°C due to the endothermic dissolution of the sorbitol,

[0129] (e) The temperature is set / kept at 60°C (using for example a water bath / Bain Marie) and the foam material is maintained at this temperature,

[0130] (f) Ingredient 6 (flavor) is added in the amounts shown in Table 1 and stirred, and

[0131] (g) Ingredient 7 (functional emulsion) is added in the amounts shown in Table 1 and stirred.

[0132] The foam material can be kept at 60°C for a time period of up to 5 hours without significant deterioration. The foam material can be dispensed into a mold and allowed to cool, where it forms a solid flexible material.

[0133] Determination of antimicrobial effect:

[0134] The total weight of the formulation in Example 1 was 279.5 grams, containing 4 grams of functional emulsion (1.4%). The functional emulsion contained 10% free caprylic acid in the oil phase, so the concentration of free caprylic acid in the formulation of Example 1 was 0.14%.

[0135] The following results were obtained from the antimicrobial assay as described in the Materials and Methods section above:

[0136]

[0137] Example 2 - Egg white / gelatin / agar formulation using an oil-in-water emulsion as a functional ingredient

[0138] In this example, a combination of gelatin and agar was used to modulate the solubility and heat resistance of the whipped egg white formulation. Gelatin begins to melt at temperatures in the range of 35°C, and if the storage temperature exceeds the melting temperature of the gelatin (35°C), the stability of the finished formulation with only gelatin as a gelling agent can flow and deform. Agar is a polysaccharide gel that melts at 80°C and remains liquid at temperatures as low as 45°C. In combination with gelatin, the characteristic hysteresis of agar can be used to improve the thermal stability of the formulation without losing the low temperature solubility of the gelatin. Glycerol was added in this example to prevent excessive drying, the humectant effect of which preserves residual water.

[0139] Table 2: Foam egg white base formulation of Example 2

[0140] Ingredients Weight in grams 1 Pure water 300 2 Citric acid 1.0 3 Agar 7.6 4 Gelatin 260 bloom 20 5 Pure water 50 6 Glycerol 25 7 Egg white whipped to firm peak at 20% protein concentration 50 8 Spice powder 8 9 Functional emulsion based on US patent application 15 / 384,372 10 Total weight 471.6

[0141] A foam egg white matrix comprising a functional emulsion was prepared according to the following method;

[0142] (a) In a separate container - ingredients 5 (purified water) and 6 (glycerol) from Table 2 were combined in the appropriate container in the amounts shown,

[0143] (b) In a separate container - ingredients 5 (purified water) and 6 (glycerol) from Table 2 were combined in the appropriate container in the amounts shown,

[0144] (c) Using a suitable grade of equipment with a whipping attachment, ingredient 7 (20% egg white) from Table 2 in the amount shown was whipped / beaten in an appropriate container for approximately 5 minutes to obtain a foam material that held its shape - a firm peak when pulled upwards,

[0145] (d) When the mixture from step (a) reached 90°C and the agar had melted, the glycerol-water mixture from step (b) was added and mixed thoroughly. The temperature would drop to approximately 70°C and step (e) was immediately carried out,

[0146] (e) 50 grams of the mixture from step (c) was added to the mixture from step (d) and stirred vigorously and continuously while heating until the temperature exceeded 80°C at which point the heating was turned off and / or the mixture was removed from the heat,

[0147] (f) Ingredient 8 (flavour) from Table 2 was added in the amount shown and stirred, and

[0148] (g) Ingredient 9 (functional emulsion) from Table 2 was added in the amount shown and stirred.

[0149] The foam material could be held at 60°C for a period of up to 5 hours without significant deterioration. The foam material could be dispensed into a mould and allowed to cool where it formed a firm flexible material.

[0150] Determination of antimicrobial effect

[0151] The total weight of the materials in the formulation in Example 2 was 471.6 grams containing 10 grams of functional emulsion (2.12%). The concentration of caprylic acid in the functional emulsion was 10% so the concentration of free caprylic acid in the formulation was 0.17%.

[0152] The results of the antimicrobial assay as described in the Materials and Methods section above were as follows:

[0153]

[0154] Example 3 - Constructing a formulation with a functional emulsion precursor in egg white foam

[0155] In this example, a whipped egg white foam containing lecithin and sodium caprylate was constructed as a combination of a precursor to the functional emulsion disclosed in Folan U.S. Patent Application 15 / 384,372. After a bake-set stage, the inactive water-soluble sodium caprylate was converted to active oil-soluble caprylic acid using an organic acid, converting the precursor to the active form of the emulsion. In addition to the need to construct the functional emulsion separately for dispensing, constructing the precursor into the egg white foam prior to bake-setting it provides a much greater assurance that the functional ingredients are concentrated in the foam air interface upon cooling. The separate addition of the fully formed emulsion depends on migration driven by phase repulsion in order to concentrate the oil droplets at the surface of the foam bubbles.

[0156] Table 3: Foamed egg white matrix formulation of Example 3

[0157]

[0158] A foamed egg white matrix containing a precursor to a functional emulsion was prepared according to the following method;

[0159] (a) Combine ingredients 1 (purified water) and 2 (lecithin) from Table 3 in the amounts shown in a suitable container at room temperature and allow about 10 minutes to hydrate,

[0160] (b) Add ingredient 3 (sodium caprylate) from Table 3 in the amount shown and allow sufficient time to fully dissolve before proceeding,

[0161] (c) Add ingredient 4 (egg white powder) from Table 3 in the amount shown and wet out completely using a spatula and allow about 30 minutes to fully hydrate,

[0162] (d) In a separate suitable container, combine ingredients 5 (purified water), 6 (agar) and 7 (gelatin) from Table 3 in the amounts shown and allow about 30 minutes to fully hydrate, then heat the mixture to about 90°C using a thermocouple in the material to confirm the temperature,

[0163] (e) When the mixture from step (d) reaches temperature, whip / paddle the fully hydrated composition from step (c) using a suitable grade of equipment with a beater attachment for about 5 minutes to obtain a foam material that holds its shape - a firm peak when pulled upward, forming ingredient 10,

[0164] (f) When the mixture from step (d) reaches about 90°C and the agar has melted, combine ingredients 8 (purified water) and 9 (glycerol) from Table 3 in separate containers in the amounts shown and add to the mixture from step (d) with good agitation. The temperature will drop to about 70°C and step (g) will be performed immediately,

[0165] (g) Add 50 grams of the mixture from step (e) (ingredient 10) to the mixture from step (d) and stir vigorously while heating and continue to stir until the temperature exceeds 80°C at which time the heat is turned off and / or the mixture is removed from the heat,

[0166] (h) Add ingredient 11 (flavor) from Table 3 in the amount shown and stir to dissolve, and (i) Add ingredient 12 (citric acid powder) from Table 3 in the amount shown and stir well and allow sufficient time to dissolve and check the pH to ensure it is less than 5.0.

[0167] The foamed mass can be held at 60°C for a period of up to 5 hours without significant deterioration. The foamed mass can be dispensed into molds and allowed to cool where it forms a firm flexible material.

[0168] Determination of antimicrobial effect:

[0169] The total weight of the formulation in Example 3 was 454.2 grams containing 0.736 grams of sodium caprylate (0.16%) in 50 grams of whipped egg white. The molecular weight of sodium caprylate is 166.19 and the molecular weight of caprylic acid is 144.21 and the conversion factor is 1.15, so if all of the dose load of sodium caprylate is converted to free caprylic acid upon acidification, the concentration of free caprylic acid in the formulation is 0.14%.

[0170] The antimicrobial assay as described in the Materials and Methods section above gave the following results:

[0171]

[0172] Example 4 - Development of an alternative method for egg white foam

[0173] In some cases where suitable whipping equipment is not readily available, it is possible to generate sufficient protein foam using hydrogen peroxide and catalase. Much more concentrated egg white protein is required as well as gelatin that is fully hydrated at room temperature. Hydrogen peroxide is available as 8%, 16% and 32% solutions, the higher concentrations presenting a significant chemical burn hazard if accidentally splashed onto human skin. The optimal amount of hydrogen peroxide depends on the concentration in the solution and the ambient temperature. Catalase is commercially available and approved for food use. Very small amounts of the enzyme are required to activate the breakdown of peroxide, generating a relatively large amount of oxygen dispersed in the entire egg white gelatin mass. Continuous agitation is required to maintain the foam and heating should be initiated to bake the solidification when the peroxide reaction ceases.

[0174] Table 4: Foam egg white base formulation of Example 4

[0175]

[0176]

[0177] A foam egg white base containing a functional emulsion was prepared according to the following method;

[0178] (a) At room temperature, ingredients 1 (pure water) and 2 (gelatin) from Table 4 were combined in the amounts shown in a suitable container and allowed about 30 minutes for the gelatin to hydrate,

[0179] (b) Ingredient 3 was prepared by adding 40 grams of egg white to 60 grams of water, using a spatula to carefully wet the powder and allow it to fully hydrate over a period of about 30 minutes,

[0180] (c) The mixtures from steps (a) and (b) were combined and blended together,

[0181] (d) Ingredient 4 (hydrogen peroxide) from Table 4 was added to the mixture from step (c) in the amount shown and blended thoroughly, then ingredient 5 (catalase) from Table 4 was added in the amount shown and blended thoroughly, the foaming reaction began within a minute and continued for a period of about 5 minutes during which the foam mass was continuously stirred,

[0182] (e) Heating was initiated while constant stirring was maintained and a suitable thermocouple was used in the foam, and the foam mass was brought to 80°C,

[0183] (f) Ingredient 6 (sorbitol) from Table 4 was added in the amount shown and stirred. The foam mass cooled to about 60°C due to the endothermic dissolution of the sorbitol,

[0184] (g) The temperature of the foam mass was maintained (using a water bath or Bain Marie) at 60°C, and

[0185] (h) Add ingredient 7 (flavor) from Table 4 in the amount shown and stir.

[0186] The foam mass can be held at 60°C for a period of up to 5 hours without significant deterioration. The foam mass can be dispensed into a mold and allowed to cool where it forms a solid flexible material.

[0187] Determination of antimicrobial effect:

[0188] The total weight of the formulation in Example 4 was 263.7 grams containing 4 grams of functional emulsion (1.5%). The functional emulsion contained 10% free caprylic acid in the oil phase, therefore the concentration of free caprylic acid in the formulation of Example 4 was 0.15%.

[0189] The antimicrobial assay as described in the Materials and Methods section above gave the following results:

[0190]

[0191]

[0192] Example 5 Egg white / gelatin / agar / chelator formulation using an oil-in-water emulsion as the functional ingredient

[0193] Sodium hexametaphosphate is used as a chelator in combination with amplified citric acid to counteract its inherent alkalinity.

[0194] Table 5: Foam egg white base formulation of Example 5

[0195] Ingredients Weight in grams 1 Pure water 350 2 Citric acid monohydrate 2.0 3 Agar 7.6 4 Gelatin 260 bloom 40 5 Sorbitol 60 6 Egg white whipped to firm peak at 20% protein concentration 45 7 Spice powder 6 8 Sodium hexametaphosphate 4 9 Functional emulsion based on US patent application 15 / 384,372 10 Total weight 520.6

[0196] A foam egg white base containing a functional emulsion was prepared according to the following method;

[0197] (a) Combine ingredients 1 (purified water), 2 (citric acid monohydrate) and 3 (agar) from Table 5 in the amounts shown in a suitable vessel at room temperature and allow to hydrate for about 10 minutes, then heat to about 80°C, using a thermocouple in the mass to confirm temperature.

[0198] (b) In a separate vessel - combine ingredients 4 (gelatin) and 5 (sorbitol) from Table 5 with ingredient 3 (sodium caprylate) in the amounts shown and blend as a dry powder,

[0199] (c) Using a suitable grade of equipment with a whipping attachment, whip / beat the amount of ingredient 6 (20% egg white) from Table 5 in a suitable vessel for about 5 minutes to obtain a foam mass that holds its shape - a solid peak when pulled upward.

[0200] (d) When the mixture from step (a) reaches a temperature of about 80°C and the agar has melted, add the powder mixture from step (b) while constantly stirring. The temperature will drop to about 60°C and step (e) is immediately performed,

[0201] (e) Add 45 grams of the mixture from step (c) to the mixture from step (d) and stir vigorously and continue to stir while heating until the temperature exceeds 80°C at which point the heating is turned off and / or the mixture is removed from the heat,

[0202] (f) Add ingredient 7 (flavor) from Table 5 in the amount shown and stir, then add ingredient 8 (sodium hexametaphosphate) from Table 5 in the amount shown and stir, then add ingredient 9 (functional emulsion) from Table 5 in the amount shown and stir, and check the pH is below 5.0.

[0203] The foamed mass can be held at 60°C for a period of up to 5 hours without significant deterioration. The foamed mass can be dispensed into a mold and allowed to cool where it forms a solid flexible material.

[0204] In other embodiments, sorbitol can be replaced with an equivalent amount of erythritol or another polyol, if desired.

[0205] Determination of antimicrobial effect

[0206] The total weight of the formulation in Example 5 was 520.6 grams, containing 10 grams of functional emulsion (1.9%).

[0207] Using the antimicrobial assay as described in the Materials and Methods section above, the antimicrobial effect was similar to Example 2, with a 1.6 log reduction in viability after 1 minute of exposure.

[0208] Table 6: Summary of antimicrobial efficacy

[0209] Example 1 Example 2 Example 3 Example 4 Staphylococcus aureus inoculum 1.7 x 10 9 ]]> 2.8X10 9 ]]> 1.83X10 9 ]]> 2.66X10 8 ]]> Survival count at zero time in assay 1.35X10 6 ]]> 1.9 X 10 6 ]] 2.54 x 10 6 ]] 1.95X10 5 ]]> Survival count at one minute exposure 2.2 x 10 4 ]] 2.8X10 4 ]]> 1.97X10 3 ]]> 2.58X10 3 ]]> One minute log reduction -1.39 Log -1.33 Log -2.1 Log -1.3 Log Percent caprylic acid 0.14 0.17 0.14 0.15 Percent maximum effect 66 63 100 62

[0210] Except for Example 3, the percent difference in log reduction in Examples 1, 2, and 4 is roughly consistent with the caprylic acid content, allowing for experimental error. Notably, Example 3, which has the same concentration of caprylic acid as Example 1, exhibits a 34% greater effect. While not wishing to be bound by explanation, this suggests that the increased efficacy in Example 3 compared to Example 1 is due to improved release and available dose at the magnified surface of the whipped egg white, which is due to the more highly dispersed nature of the caprylic acid formed in situ compared to its droplet form when incorporated as an emulsion.

[0211] Example 6: Synergistic antimicrobial effect of polyphosphate when combined with functional emulsion of free fatty acid

[0212] An example of a polyphosphate comprising hexametaphosphate as a chelating agent is exemplified in Example 5, which includes sodium hexametaphosphate (“SHMP” or “HMP sodium”). When evaluating the antimicrobial effect of the formulation in Example 5, it was surprisingly discovered that the combination of the functional free fatty acid emulsion works synergistically with the hexametaphosphate.

[0213] All mineral chelators will affect the growth inhibition of bacteria, particularly if essential minerals such as calcium, magnesium, zinc, and iron are limited in the medium, which they do by chelating the essential minerals. The growth inhibition of the chelators can be easily overcome by supplementing the growth medium with the essential minerals.

[0214] As exemplified in Examples 1-5 of the present application, the functional emulsion of free fatty acids disclosed in U.S. Patent Application 15 / 384,372 exert an effective antimicrobial effect. It was surprisingly discovered that the functional emulsion amplifies the growth inhibition of polyphosphates and also in the presence of supplemental calcium, which would otherwise inhibit the effect of hexametaphosphate.

[0215] To illustrate the synergy of the combination of the functional emulsion and hexametaphosphate, it is necessary to construct formulations of both at and below their minimum inhibitory concentrations, and then to combine these in a manner to measure amplification greater than might be expected as additive.

[0216] In this example, a formulation of the functional emulsion was constructed using 8% W / W caprylic acid and 2% W / W mixed capric / caprylic acid triglyceride (Miglyol 812N from IOI Oleo, Germany) in the oil phase using 1.56% w / w lecithin and 0.15% Tween 80 as co-surfactants, using the method disclosed in U.S. Patent Application 15 / 384,372.

[0217] The test organism was Staphylococcus aureus NCTC 8325-4 as described in the Methods section, and the flask culture was 100 mL Luria-Bertani Broth (LB Broth) in a 250 mL Erlenmeyer flask. LB Broth was used in place of brain heart infusion broth because it is more defined and limited in mineral content.

[0218] The standard inoculum was grown as described in the Methods section and adjusted to 1 x 10 6 viable cell count by dilution in sterile saline, and 0.1 ml of this was used to aseptically inoculate a 100 ml volume of test medium - the inoculum in the test flask was 1 x 10 3 .

[0219] The minimum inhibitory concentration of the functional emulsion was determined using the agar dilution method, in which LB agar plates of progressively increasing dilutions of the functional emulsion were streaked with the test organism and visually assessed for growth after incubation at 37°C for 24 hours.

[0220] The results are shown in Table 7.

[0221] Some growth was still detected at 0.5%, so the minimum inhibitory concentration can be considered to be greater than 0.5%: a concentration of 0.375 had no inhibitory effect on growth and this concentration was selected for further study in combination with hexametaphosphate.

[0222] Table 7: Minimum inhibitory concentration of functional emulsion against Staphylococcus aureus NCTC 8325-4

[0223] Emulsion weight % Growth observation results 1.56 No growth 1.25 No growth 0.937 No growth 0.625 No growth 0.563 No growth 0.5 Trace needle-like colonies 0.438 Almost no needle-like colonies 0.375 Flower-like growth 0.313 Flower-like growth 0 Flower-like growth

[0224] To determine the minimum inhibitory effect of hexametaphosphate, a series of flasks with 100 ml of LB broth were each supplemented with hexametaphosphate at a concentration ranging from 0% W / W to 1% W / W, and each flask was inoculated with a standard inoculum so as to reach 1 X 10 3 viable bacteria, the flasks were incubated at 37°C in a rotary incubator for 24 hours and at this time the growth was visually assessed. As shown in the first row of Table 8, growth was evident only in the flasks with zero concentration of hexametaphosphate, and at all concentrations of 0.05% and above, growth was clearly inhibited.

[0225] After the visual assessment, 0.5% sterile calcium chloride was added to all the flasks and incubation was continued for a further 24 hours. Visual inspection 24 hours after the addition of calcium chloride showed complete growth in all flasks up to and including 0.27% hexametaphosphate. Hexametaphosphate concentrations including and above 0.5% hexametaphosphate remained inhibitory. From this data it can be seen that 0.27% hexametaphosphate will inhibit growth unless the medium is supplemented with at least 0.5% calcium chloride, in which case there is no inhibitory effect on growth.

[0226] Table 8: Effect of sodium hexametaphosphate on Staphylococcus aureus growth in liquid culture

[0227]

[0228] However, if the medium is further supplemented with 0.375% functional emulsion (a concentration that has no inhibitory effect on growth itself), then the complete growth inhibition will be restored.

[0229] When the functional emulsion, in this case an oil-in-water emulsion consisting of highly dispersed droplets of octanoic acid oil in water, stabilized with purified amphiphilic lecithin and optionally other ingredients such as a co-surfactant (hereinafter "ML:8") is supplemented, the synergy is exemplified in the data presented in Table 9 below.

[0230] Table 9: Synergy of ML:8 Hexametaphosphate

[0231] Flask 12h 24h 24H CFU / ml 1 Control + + >10 9 ]] 2 0.375% functional emulsion + + >10 8 ]] 3 0.5% calcium + + >10 9 <!-- 21 -->]]> 4 0.27% SHMP - - ~2x10 2 ]] 5 0.27% SHMP + 0.5% calcium + + >10 9 ]] 6 0.375% functional emulsion + 0.5% calcium chloride + + >10 8 ]] 7 0.27% SHMP + 0.5% calcium + 0.375% functional emulsion - - ~2x10 2 ]]>

[0232] Row 1 in Table 9 is a control flask containing Luria-Bertani (LB) broth and standard inoculum, the terminal plate count showing complete growth with greater than 10 9 live organisms per milliliter.

[0233] Row 2 in Table 9 is the same LB broth with the same inoculum supplemented with 0.375% functional emulsion, there is flower-like growth at 12 hours and 24 hours, and the terminal plate count shows only one log less viable cells than the control: a one log reduction.

[0234] Row 3 in Table 9 is a control of calcium chloride, showing that this supplement has no effect on growth, the terminal count is the same as the control.

[0235] Row 4 in Table 9 illustrates that 0.27% hexametaphosphate completely inhibits growth, the residual viability is 2 X 10 2 , which is essentially the inoculum that remains viable, although inhibited (the microbial inhibition is not a microbiocidal effect).

[0236] Row 5 in Table 9 is the same as row 4 supplemented with 0.5% calcium chloride, showing a complete reversal of the inhibitory effect of hexametaphosphate, the terminal viability is the same as the control in this row.

[0237] Row 6 in Table 9 is the same as row 2 supplemented with 0.5% calcium chloride, the terminal viability is the same as row 2, with a one log reduction - the addition of calcium chloride at the concentration used in this example does indeed magnify or inhibit the effect of the functional emulsion.

[0238] Row 7 in Table 9 is a combination of row 2 (no inhibition) and row 5 (no inhibition), which shows complete inhibition, the residual viability is only 2 X 10 2 , which is the inhibited inoculum that remains viable throughout the test procedure.

[0239] It can be concluded that sodium hexametaphosphate has no inhibitory effect on microbial growth in the presence of excess calcium. Similarly, 0.375% functional emulsion has no inhibitory effect on microbial growth under similar conditions. Taken together, both components (functional emulsion and sodium hexametaphosphate) act synergistically to completely inhibit microbial growth in the presence of excess calcium.

[0240] Similar synergistic effects can be demonstrated using other polyphosphates, including but not limited to, disodium orthophosphate, uridine monophosphate, and sodium inositol hexaphosphate. Using the methods described to generate the data in Table 8, the threshold limit for combinations of 0.75% disodium orthophosphate and 0.2% sodium inositol hexaphosphate with 0.5% calcium chloride was identified. No results were determined for uridine monophosphate at 1%, suggesting that its chelating properties are less robust.

[0241] Using similar methods, the threshold limit for combinations of non-phosphate chelators, including trisodium citrate and ethylenediaminetetraacetic acid with 0.5% calcium chloride were 0.5% and 0.25%, respectively.

[0242] It should be noted that the ionic binding properties of many chelators are pH dependent, particularly in the case of trisodium citrate, which is an organic acid salt that dissociates at pH below 6.0.

[0243] Those skilled in the art will appreciate that the ratios of chelator / calcium chloride / functional emulsion provided in this example have been selected as most suitable to measure the example synergistic effect by comparison. This same synergistic effect is exhibited in all combinations of the same ingredients, even though excess of any one ingredient can preclude its measurement.

[0244] Example 7 Alternative formulations using functional emulsion precursors in egg white foam

[0245] An exemplary formulation of a foamed egg white matrix has the composition disclosed in Table 10.

[0246] Table 10: Exemplary foamed egg white matrix formulation of Example 7

[0247]

[0248]

[0249] In embodiments, the sugar is saccharin.

[0250] In embodiments, the flavor is vanillin.

[0251] In embodiments, the functional ingredient is HMP sodium.

[0252] In one embodiment, the delivery system comprises an egg white matrix formulation as disclosed in Table 11.

[0253] Table 11: Foam egg white matrix formulations

[0254] Ingredients Weight in grams 1 Water 210 2 Glycerol 50 3 Lecithin S75 from Lipoid AG 1 4 Sodium caprylate 2.32 5 Agar 5 6 Sorbitol 40 7 Gelatin 10 8 Whipped egg white (20% W / W protein) 10 9 Sodium HMP 1 10 Saccharin 1 11 Vanillin 2 12 Citric acid 2 Total weight 334.32

[0255] In one embodiment, the delivery system comprises egg white matrix formulations as disclosed in Table 12.

[0256] Table 12: Foam egg white matrix formulations

[0257] Ingredients Weight in grams 1 Water 215 2 Glycerol 50 3 Lecithin S75 from Lipoid AG 0.5 4 Sodium caprylate 1.16 5 Agar 6.5 6 Sorbitol 30 7 Gelatin 20 8 Whipped egg white (10% W / W protein) 30 9 Sodium HMP 2 10 Saccharin 2 11 Vanillin 4 12 Citric acid 3 Total weight 364.16

[0258] Example 8 Alternative formulations using functional emulsion precursors in egg white foam

[0259] Exemplary formulations of foam egg white matrixes have the compositions disclosed in Table 13.

[0260] Table 13: Exemplary foam egg white matrix formulations of Example 8

[0261]

[0262]

[0263] In embodiments, the sugar is saccharin.

[0264] In embodiments, the flavor is vanillin.

[0265] In embodiments, the functional ingredient is HMP sodium. In other embodiments, no functional ingredient other than the functional emulsion is added.

[0266] In embodiments, the functional emulsion is an oil-in-water emulsion consisting of highly dispersed droplets of caprylic acid oil in water, stabilized with purified amphiphilic lecithin and optionally other ingredients such as a co-surfactant (hereafter "ML:8"). In other embodiments, the functional emulsion is added as a precursor mixture, comprising sodium caprylate, lecithin, Lipoid S75 and water (hereafter "ML:8 precursor"), which is converted into the active form of the emulsion after the baking solidification stage, using an organic acid to convert the inactive water-soluble sodium caprylate into the active oil-soluble caprylic acid.

[0267] In one embodiment, the delivery system comprises egg white matrix formulations as disclosed in Table 14.

[0268] Table 14: Exemplary foam egg white matrix formulations of Example 8

[0269]

[0270]

[0271] In an embodiment, the delivery system comprises an egg white matrix formulation as disclosed in Table 15.

[0272] Table 15: Exemplary foam egg white matrix formulations of Example 8

[0273] Ingredients Weight in grams 1 Water 170 2 Glycerol 50 3 Agar 6.5 4 Sorbitol 20 5 Gelatin 20 6 Whipped egg white (10% W / W protein) 30 7 Sodium HMP 2 8 Saccharin 2 9 Vanillin 4 10 Citric acid (20% W / W solution) 30 11 ML:8 precursor 18 Total weight 352.5

[0274] In an embodiment, the delivery system comprises an egg white matrix formulation as disclosed in Table 16.

[0275] Table 16: Exemplary foam egg white matrix formulations of Example 8

[0276]

[0277]

[0278] In an embodiment, the delivery system comprises an egg white matrix formulation as disclosed in Table 17.

[0279] Table 17: Exemplary foam egg white matrix formulations of Example 8

[0280] Ingredients Weight in grams 1 Water 170 2 Glycerol 50 3 Agar 6.5 4 Sorbitol 30 5 Gelatin 15 6 Whipped egg white (10% W / W protein) 30 7 Sodium HMP 2 8 Saccharin 2 9 Vanillin 4 10 Citric acid (20% W / W solution) 30 11 ML:8 precursor 18 Total weight 357.5

[0281] In an embodiment, the delivery system comprises an egg white matrix formulation as disclosed in Table 18.

[0282] Table 18: Exemplary foam egg white matrix formulations of Example 8

[0283] Ingredients Weight in grams 1 Water 170 2 Glycerol 50 3 Agar 6.5 4 Sorbitol 30 5 Gelatin 5 6 Whipped egg white (10% W / W protein) 30 7 Sodium HMP 2 8 Saccharin 2 9 Vanillin 4 10 Citric acid (20% W / W solution) 30 11 ML:8 precursor 18 Total weight 347.5

[0284] In an embodiment, the delivery system comprises an egg white matrix formulation as disclosed in Table 19.

[0285] Table 19: Exemplary foam egg white matrix formulations of Example 8

[0286]

[0287]

[0288] In an embodiment, the delivery system comprises an egg white matrix formulation as disclosed in Table 20.

[0289] Table 20: Exemplary foam egg white matrix formulations of Example 8

[0290] Ingredients Weight in grams 1 Water 170 2 Glycerol 50 3 Agar 6.5 4 Sorbitol 30 5 Gelatin 20 6 Whipped egg white (10% W / W protein) 30 8 Sodium HMP 2 9 Saccharin 4 10 Vanillin 15 11 Citric acid (20% W / W solution) 2.25 ML:8 precursor Total weight Ingredients Weight in grams Water Glycerol Agar Sorbitol Gelatin Whipped egg white (10% W / W protein) Saccharin Vanillin Citric acid (20% W / W solution) ML:8 precursor Total weight 329.75

[0291] In an embodiment, the delivery system comprises an egg white matrix formulation as disclosed in Table 21.

[0292] Table 21: Exemplary Foam Egg White Base Formulation of Example 8

[0293]

[0294]

Claims

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) Egg white components containing 1-50% protein; ii) At least two heat-resistant and / or heat-sensitive gelling agents, wherein the two gelling agents are gelatin and agar, wherein the ratio of gelatin to agar ranges from 1:1 to 10:1; iii) pH adjuster; iv) One or more plasticizers and / or humectants; and v) One or more water sources.

2. The delivery system of claim 1, wherein the at least two or more gelling agents further comprise pectin.

3. The delivery system of claim 1, wherein the pH adjuster is citric acid.

4. The delivery system of claim 1, wherein the one or more functional ingredients comprise a functional emulsion.

5. The delivery system of claim 1, comprising two or more functional components.

6. The delivery system of claim 4, further comprising a chelating agent.

7. The delivery system of claim 6, wherein the chelating agent is a polyphosphate.

8. The delivery system of claim 7, wherein the polyphosphate is sodium hexametaphosphate.

9. The delivery system of claim 1, wherein the one or more functional ingredients are selected from drugs, nutritional supplements, hormones, proteins, and antigens.

10. The delivery system of claim 1, wherein the one or more functional ingredients are selected from botanical therapeutics, vitamins, minerals, enzymes, and peptides.

11. The delivery system of claim 1, further comprising a buffer, a natural or artificial flavoring agent, a coloring agent, or a combination thereof.

12. The delivery system of claim 1, further comprising a sweetener.

13. A canine dual-action dental prosthesis, wherein the dental prosthesis comprises two components: a flexible matrix and a filling, and wherein the filling comprises a delivery system according to claim 1, wherein the flexible matrix is ​​shaped and designed to reduce plaque and tartar through mechanical action during chewing, and wherein the dental prosthesis matrix is ​​characterized by a reservoir / cavity for the filling.

14. The canine dual-action molar of claim 13, wherein the flexible matrix is ​​bony and has ridges and nodules on at least a portion of the exposed surface area.

15. The canine dual-action molar of claim 14, wherein the delivery system comprises a functional component comprising an emulsion comprising (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 salts thereof.

16. The canine dual-action dental molar of claim 15, wherein the emulsion comprises (a) sodium caprylate or sodium caprylate and (b) defatted lecithin.

17. Use of the delivery system according to any one of claims 1-10 in the preparation of a pharmaceutical product or nutritional product for oral administration of one or more functional ingredients to an animal in need.

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