Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
  • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
• • A—HUMAN NECESSITIES
  • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
  • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
  • A23L27/00—Spices; Flavouring agents or condiments; Artificial sweetening agents; Table salts; Dietetic salt substitutes; Preparation or treatment thereof
  • A23L27/70—Fixation, conservation, or encapsulation of flavouring agents
  • A23L27/72—Encapsulation
• • A—HUMAN NECESSITIES
  • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
  • A23P—SHAPING OR WORKING OF FOODSTUFFS, NOT FULLY COVERED BY A SINGLE OTHER SUBCLASS
  • A23P10/00—Shaping or working of foodstuffs characterised by the products
  • A23P10/30—Encapsulation of particles, e.g. foodstuff additives

Definitions

• This application relates to a modified functional ingredient which is microencapsulated by an enteric matrix and methods for making the same. More particularly, the modified functional ingredient is microencapsulated in an aqueous environment which is substantially free of organic solvents.
• Enteric delivery systems are commonly utilized when the functional materials or medicaments are known to be sensitive to certain conditions such that they become less effective or if the functional materials cause problems for the user, such as stomach problems with aspirin.
• enteric delivery as most common in pharmaceutical practice, is accomplished using coated tablets and gel capsules. However, those particular delivery methods are not well suited for food applications. In particular, neither tablets nor capsules are sized to be integrated into most existing food products.
• microencapsulation An alternative process for enteric delivery is microencapsulation.
• Microencapsulation is generally performed using specialized equipment or in an environment including organic solvents. These methods require additional capital expenditures and the use of additional materials, such as the organic solvents, which may or may not be usable in subsequent microencapsulation cycles. As a result, the process of microencapsulation requires investments in both equipment and organic solvent procurement and disposal.
• microencapsulation efficiency of the process. Generally, a certain significant percentage of the material to be microencapsulated is not captured. The uncaptured material may be recovered for reuse, recycled, or a percentage of the uncaptured material remains adhered to the outer surface of the microencapsulated particulates.
• the product tends to have a taste profile associated with the uncaptured material, which is often undesirable.
• the uncaptured material includes oxidizable triglycerides such as unsaturated and polyunsaturated lipids, oxidizable flavors and essential oils, or other organic compounds that may naturally have undesirable taste and/ or flavor.
• composition includes a functional ingredient microencapsulated in an enteric matrix, such as described in U.S. Patent Application Serial No. 12/479,454, which is
• the enteric matrix includes one or more food grade polymer (s), and the functional ingredient includes a modified functional ingredient
• the functional ingredient is homogeneously dispersed throughout the enteric matrix material.
• the functional ingredient includes at least about 30 percent modified compounds.
• the modified compound includes at least one of a salt, glycoside, complex or ester of an essential oil, such as linalool and thymol.
• a method of microencapsulating a modified active or functional ingredient includes agitating or mixing water, an enteric matrix material, and an emulsif ier to form a combination at a pH that maintains complete dissolution of the enteric matrix material being utilized, hi one approach, the combination is substantially free of organic solvents.
• a functional ingredient including a modified portion is added to the combination and homogenized to create a fine, stable emulsion.
• the emulsion is then treated with an acid and/or other cross-linking or precipitating agents, depending on the enteric matrix material being used, such as calcium, under controlled mixing conditions and in an amount and at a rate effective to form a particulate precipitate.
• the functional ingredient is homogeneously dispersed throughout the precipitate and with an improved
• FIG. 1 illustrates a method for microencapsulating a functional ingredient
• FIG. 2 is a chart comparing the microencapsulation efficiency between two experiments, with one experiment including a functional ingredient that does not contain at least 30 percent esters, the second experiment including a functional ingredient that includes at least 30 percent esters of linalool and thymol;
• FIG.3 is a table showing the known empirical formula, solubility in water, vapor pressure, partition coefficient and a ratio comparing the affinity for oil to water ratio of various esters;
• FIG.4 is a graph illustrating the percentage release of the various components of a functional ingredient which does not include esters with an enteric matrix comprised of 95 percent shellac and 5 percent zein;
• FIG.5 is a graph illustrating the percentage release of the various components of a functional ingredient including esters with an enteric matrix comprised of 95 percent shellac and 5 percent zein;
• FIG. 6 is a graph illustrating the percentage release of the various components of a functional ingredient comprising linalyl acetate within an alginate/ shellac enteric matrix in a digestion model simulating stomach and small intestine conditions;
• FIG. 7 is a graph illustrating the percentage release of the various components of a functional ingredient comprising linalyl butyrate within an alginate/ shellac enteric matrix in a digestion model simulating stomach and small intestine conditions.
• the functional ingredients can have undesirable taste or flavor profiles.
• modifying the functional ingredient can mask or change the undesirable tastes and/ or flavors while retaining the proper ratios of the functional ingredients ensuring bioavailability and efficacy.
• the functioned ingredient to be microencapsulated can include modified forms of essential oils, such as thymol and linalool. Modifications to the functional ingredient may include a variety of forms that modify the perceived taste and/ or organoleptic properties of the functional ingredient.
• the modification may cause a change to the flavor and/ or taste threshold of the functional ingredient.
• the modification causes a change to the volatility and/ or vapor pressure of the modified functional ingredient with respect to the non-modified, parent form of the functional ingredient.
• the organoleptic properties of the modified form may include a higher taste threshold.
• a modified functional ingredient on the surface of the enteric matrix may produce a less undesirable flavor profile than the presence of unmodified functional ingredients.
• modifications may include salt, glycoside, complex and/or esterification of the functional ingredient.
• the modified form of the functional ingredient When ingested and released in the intestinal tract, the modified form of the functional ingredient reverts back, at least in part, into the parent form and provides the same functional benefits as if the parent functional ingredient was microencapsulated and consumed.
• the modified functional ingredient hydrolyzes from the modified form back into the parent, non-modified form of the functional ingredient during digestion. Further, the modified forms of the functional ingredient can provide additional benefits as will be discussed further below.
• the modified form may make up varying percents of the overall functional ingredient composition.
• the modified form comprises at least 10% of the functional ingredient composition.
• the modified form comprises at least 30% of the functional ingredient composition.
• the modified form comprises at least 50% of the functional ingredient composition.
• esters are generally known to produce less undesirable flavors, and therefore any flavors produced would not result in a wholly undesirable organoleptic flavor profile. Further, due to the low water solubility and/ or increased hydrophobicity of the modified functional ingredients including an ester, particularly in reference to the parent non-esterified functional ingredients, the below described method can result in a higher microencapsulation efficiency, as can be shown by a higher payload and retention rate, than has been recognized in the absence of esterified functional ingredients.
• Examples of the use of the product created by the methods described herein are aimed at delivery in a powdered soft drink (PSD) beverage.
• Other exemplary uses of the product include other food products, such as biscuits, bars, ice cream, snacks, instant meals and the like.
• FIG. 1 A method for microencapsulating a functional ingredient is generally described in FIG. 1.
• Enteric delivery within a food matrix is achieved by the formation of matrix particles with the dispersed portion being that of the functional ingredient such as an essential oil blend with diluent triglycerides, and the matrix portion is that of food grade enteric polymers, such as shellac, zein, calcium alginate, denatured whey protein, caseinate and any and all food-grade enteric polymers.
• the functional ingredient such as an essential oil blend with diluent triglycerides
• the matrix portion is that of food grade enteric polymers, such as shellac, zein, calcium alginate, denatured whey protein, caseinate and any and all food-grade enteric polymers.
• water, an enteric matrix material and an emulsifier are mixed or agitated until the enteric matrix material and emulsifier are fully dispersed in the water 100.
• the emulsifier and enteric matrix material can be added to the water together or separately, with either being added first
• the pH is maintained at a level sufficient that allows for complete solubilization of the enteric material.
• the pH of the dispersion is generally between about 7.2 and 9.0.
• a basic material such as sodium, potassium or ammonium hydroxide
• a basic material can be added to the dispersion to raise the pH, such as within a range from about 7.2 to about 12.0, preferably 8.0 to 11.3, to guarantee and maintain complete dissolution of the enteric polymers without the use of organic solvents.
• agitation refers to the use of a top entering mixer with impeller or a rotor/ stator mixing device operating at a speed of less than 10,000 RPM.
• substantially free of organic solvent refers to an amount of added organic solvent, such as isopropanol or ethanol or any other organic solvent less than the amount required to enable solubility of the enteric material under the processing conditions.
• the amount of added organic solvent is less than about 0.1 percent by weight of the combination of water, emulsifier and enteric material.
• the water is deionized water.
• the enteric matrix material used herein is any food grade enteric polymer, or a combination of two or more food grade enteric polymers.
• the enteric matrix material is shellac, zein, calcium alginate, caseinate or combinations thereof.
• Other food grade enteric polymers include denatured whey protein.
• the prepared enteric matrix material does not contain any organic solvents.
• the emulsifier described herein may be any food grade emulsifier.
• the emulsifier is polysorbate, polyglycerol ester, sucrose stearate, sucrose esters, proteins, lecithins or combinations thereof. More particularly, the emulsifier is preferably a sucrose ester due to the creation of the smaller and most uniformly dispersed oil droplets within the later created emulsion.
• water comprises about 50 percent to about 95 percent of the dispersion by weight and preferably from about 70 to about 95 percent, and more preferably from about 80 to about 90 percent.
• the emulsifier generally comprises less than about 5 percent of the dispersion by weight, preferably from about 0.01 to about 1 percent by weight, and more preferably about 0.01 to about 0.1 percent by weight of the dispersion.
• the enteric matrix material ranges from about 1 percent to about 10 percent by weight, in other approaches from about 4 to about 7 percent, and yet in other approaches from about 5 percent to 6 percent by weight of the dispersion.
• a functional ingredient having at least a portion thereof modified, and a non-active carrier is added 200 and agitated 300 to provide a coarse emulsion having a droplet size of more than about 10 micrometers.
• the coarse emulsion is homogenized 300 to create a fine, stable emulsion.
• the fine, stable emulsion has a droplet size of less than about 10 micrometers.
• the functional ingredient and non-active carrier are homogeneously dispersed in the form of fine droplets throughout
• the combination of the functional ingredient and non-active carrier is added in amount ranging from about 2 to about 7 percent of the emulsion by weight.
• the combination of the functional ingredient and non-active carrier is added in an amount ranging from about 3 to about 6 percent of the emulsion by weight.
• the emulsion includes from about 60 to about 95 percent water.
• homogenization or ''homogenized'' refers to mixing at a speed greater than about 10,000 RPM, such as the use of a rotor/stator mixing device or at a lower mixing speed of an elevated pressure, such as a valve homogenizer operating at a pressure of about 500 psi to about 10,000 psi.
• the functional ingredient may include chemically modified compounds of essential oils.
• the functional ingredient includes chemically modified compounds of thymol and linalool.
• chemically modified compounds of thymol and linalool For example, glycosides, salts and/ or complexes of thymol and/ or linalool may be used.
• thymyl and linalyl acetate may be used.
• other fatty acid esters may be used, such as octanoate.
• Other acceptable chemically modified compounds can be used, such as butyrates, lactates, cinnamates and pyruvates.
• the functional ingredient includes alpha-pinene, para-cymene, thymyl esters or salts and linalyl esters or salts.
• one exemplary blend includes, by weight, about 18 percent canola oil, about 8 percent alpha-pinene, about 39 percent para-cymene, about 5 percent linalool acetate and about 27 percent thymyl acetate.
• the modified functional ingredient portion can comprise from about 1 to about 99 percent of the functional ingredient by weight. In some approaches, the modified functional ingredient can include from at least about 10 percent of the functional ingredient by weight and, in other approaches, about 30 percent by weight. In another embodiment, the modified functional ingredient can include from about 25 to about 65 percent of the functional ingredient by weight.
• the blend of non-active carrier and functional ingredient can include, by weight, about 15 to about 30 percent canola oil, about 1 to about 10 percent alpha-pinene, about 5 to about 25 percent para-cymene, about 5 to about 20 percent linalyl ester and about 20 to about 60 percent thymyl ester.
• the blend of non-active carrier and functional ingredient can include, by weight, about 20 to about 25 percent canola oil, about 2 to about 7 percent alpha-pinene, about 10 to about 20 percent para-cymene, about 7 to about 15 percent linalyl ester and about 35 to about 50 percent thymyl ester.
• an esterified form of a functional ingredient such as thymol and linalool
• a functional ingredient such as thymol and linalool
• any ester formed between the hydroxyl group(s) of a terpene and an organic or inorganic oxoacid (containing single or multiple oxoacid groups) may be used as the functional ingredient.
• the volatility and vapor pressure of the modified functional ingredient can impact the perception of the ingredient.
• the size of the ester group may be modified to provide a desired volatility.
• the ester linakage is at least an ethyl ester. It should be noted that larger ester groups may also be used.
• the selected esterified form may have increased functionality due to an increased rate of hydrolysis over the parent form after ingestion and release from the enteric matrix in an intestinal tract.
• Esters may be obtained from natural sources or synthesized using any suitable chemical or biochemical reactions between functional ingredients, such as thymol and linalool, and organic or inorganic oxoacids that yield esters.
• Suitable oxoacids may include carboxylic acid, amino acids, phosphoric acid, sulfuric acid, and nitric acid.
• the hydroxyl group can be derived from a homogenous source (e.g. thymol) or mixed source (thymol and linalool).
• Exemplary monocar boxy lie acids include, but are not limited to, acetic, propionic, butyric, pentanoic, hexanoic, decanoic, stearic, lactic, cinnarnic, pyruvic, benzoic, and gluconic acids.
• Exemplary dicarboxylic acids include, but are not limited to, oxalic, malonic, maleic, fumaric, tartaric, succinic, glutaric, glucaric, adipic, pimelic, suberic, azelak, and sebacic acids.
• Exemplary tricarboxylic acids include, but are not limited to, citric and isocitric acids.
• Other exemplary esters that may be formed by reactions of terpenes with oxoacids include dithymol succinate, dithymol adipate, and dithymol sebacate.
• the modified functional ingredient can include an ester formed, regardless of chemical or biochemical reaction approach for its preparation, between terpene esters and other esters.
• the functional group can be formed using
• the functional group can include an ester formed by reacting thymol acetate with methyl octanoate or tripalmitdn.
• the functional ingredient can include other modified compounds.
• the modified functional group can include any glycoside formed by chemical or biochemical reaction between the hydroxyl group(s) of a terpene and a single sugar group (monosaccharide) or several sugar groups (oligosaccharide).
• thymol and/ or linalool glycosides can be the modified functional ingredient
• the sugar group can include any glycoside with the glycone portion composed of mono-, di- tri- compassion and/ or polysaccharides of any kind and the aglycone portion being any hydroxy-terpene (e.g. thymol, linalool).
• the sugar group can also include reducing sugars and/ or non-reducing sugars.
• Exemplary sugars include, but are not limited to, glucose, fructose, galactose, ribose, sucrose, mannose, maltose, lactose, and cellobiose.
• the functional group can include any ionic or nonionic salt or complex formed involving a hydroxy-terpene and another chemical species.
• thymol and linalool salts or complexes can be the modified functional ingredient.
• One example may be sodium and/ or potassium chloride.
• the modified functional ingredient may include thymol salts that do not have fixed stoichiome tries.
• thymol salts may be prepared as partial or mixed salts having different ratios of cations and thymol comprising one or more specific cations (Na+, +, Mg++, etc.) to prepare solid complexes.
• the solidified complexes may or may not be obtained in crystalline form.
• the salt or complex may be formed by any suitable method, but in some cases is ormed by a chemical reaction or association between one or more hydroxy-terpene and one or more alkaline reagent.
• exemplary alkaline reagents may include, but are not limited to, alkaline hydroxide, oxide, or carbonate.
• the salt or complex can include any alkali metal, alkaline earth metal, or transition metal element, or combination thereof.
• Suitable salts or complex for use in foods may include sodium, potassium, lithium, calcium, magnesium, iron, manganese, zinc, and aluminum
• Other exemplary salts include any mono-, di-, or bivalent salt of thymol, including sodium thymolate (e.g. sodium thymoxide) and any mono-, di-, or bivalent salt of phenol, including calcium phenoxide.
• the functional ingredient may include various forms of modification that are combined.
• a portion of the modified functional ingredient composition may include one or more of salts, glycosides, complexes and esterified forms of one or more essential oils.
• the functional ingredient may include a mixture of any essential oils as described herein. Further, the functional ingredient can be selected to include materials which are desired to be released enterically. As an example, the functional ingredient can include compositions described in U.S. Patent Publication No.2008/0145462 to Enan. For example, the functional ingredient includes about 25 to about 35 percent by weight
• para-cymene about 1 to about 10 percent by weight linalool, about 1 to about 10 percent by weight alpha-pinene, about 35 to about 45 percent by weight thymol, and about 20 to about 30 percent by weight soybean oil.
• the functional ingredient described herein can include compounds which possess functional properties, such as anti-parasitic, anti-protozoan, and anti-fungal.
• the organic compounds further include alpha-pinene and para-cymene.
• organic compounds are blended with a non-active carrier such as a lipid, fatty acid, triglyceride or food grade oil, such as soybean oil or canola oil.
• a non-active carrier such as a lipid, fatty acid, triglyceride or food grade oil, such as soybean oil or canola oil.
• the process described herein includes the inclusion of a far less water soluble form of a functional ingredient, such as an esterified form or other modified form of the functional ingredient (e.g. esterified forms of thymol and linalool) as well as processes to remove unencapsulated material from the final ingredient.
• esters generally have a less negative impact on the taste/flavor of the food system than their respective parent compounds.
• complexes, glycosides and salts of essential oils have a less negative impact on the taste/flavor of the food system than their respective parent compounds.
• an ester may have higher microencapsulation efficiency, such as described above, than non-esterified parent compounds, such as thymol and linalool.
• the efficiency increases about 50 to about 200 percent over the efficiency observed when using non-esterified functional ingredients, more preferably about 100 to about 150 percent.
• esters have a higher olfactory perception threshold than the parent compounds, such that amount of esters necessary to be perceived is more than the amount of non-esterified thymol and linalool.
• the emulsion is then precipitated by titration with an acid or with a cross-linking or precipitating agent 400.
• the emulsion can be subjected to agitation.
• the emulsion is titrated with a solution of about 1 to about 5 percent calcium chloride and about 1 to about 5 percent citric acid.
• the emulsion is titrated with acid in an amount effective to decrease the pH down to the isoelectric point of the polymer present in the emulsion, such as a pH of about 7, causing phase separation and inducing precipitation of the enteric matrix out of solution with the functional ingredient being microencapsulated therein, thus creating a slurry of an aqueous solution and precipitate.
• the precipitated slurry has a particle size from about 1 to about 1000 micrometers, in some cases about 10 to about 500.0 micrometers, and more preferably from about 75 to about 250 micrometers.
• precipitation occurs at a pH ranging from about 3 to about 6, or further between a pH ranging from about 3.8 to about 4.6.
• the particles of enteric material such as shellac and zein
• the particles of enteric material may cross-link to like particles or to one another to form a matrix, the functional ingredient and non-active carrier being microencapsulated within the matrix.
• the functional ingredient is homogenously dispersed throughout the matrix.
• the matrix further provides a seal for the functional ingredient.
• the acid used can include any food grade acid.
• the acid is citric acid.
• composition of the enteric matrix material affects the dissolution rate and the protection provided by the enteric matrix.
• the slurry is filtered 500, washed 600 and dried 700. In one embodiment, the slurry is filtered, the resultant slurry cake is then washed and refiltered prior to drying.
• a surface oil remover is added to the slurry after filtering to aid in removing residual surface oil from the precipitate, as described in U.S. Patent Application Serial No. 12/479 ⁇ 33, which is incorporated by reference in its entirety herein. Further, the surface oil remover can also be added prior to the refiltering step.
• the precipitate is dried 700 to form a powder. Drying can be conducted such that the powder has a moisture content of less than about 10 percent, in other approaches to a moisture content of about 2 to about 6 percent, and in yet other approaches to about 3 to about 5 percent.
• the powder can be pulverized to reduce the particle size of the powder precipitate, and then further dried to a moisture content of less than about 5 percent, such as with a fluidized bed dryer.
• the resultant particles have a particle size ranging from about 1 to about 1000 micrometers, in some cases from about 10 to about 500 micrometers, and in other cases from about 75 to about 250 micrometers.
• the temperature should be maintained between about 25°C to about 70°C, and in some cases about 35°C to about 65°C. During other processing steps, it may be suitable to maintain the temperature between about 4°C to about 40°C, in other cases about 4°C to about 30°C, and in yet other cases from about 15°C to about 28°C
• modified functional ingredients such as thymyl and linalyl esters
• the payload refers to the weight percentage of the functional ingredients in relation to the final product. Therefore, an increase in payload corresponds to an increase in functional ingredient per a given amount of enteric matrix.
• the payload of the functional ingredients ranges from about 5 to about 50 percent.
• the increased payload can be attributed, at least in part, to the decreased water solubility and/ or increased hydrophobicity of a functional ingredient including modified functional ingredients, such as esters, in comparison to a functional ingredient which is not modified. Further, in some cases, large volumes of water may be used in the disclosed process.
• a modified functional ingredient, such as esters of thymol and linalool would reduce leaching of the functional ingredient due to the decreased water solubility and/ or increased
• a modified functional ingredient such as thymyl acetate, which is a liquid at room temperature (about 20 to about 25°C) would allow for easier processing since a crystalline solid ingredient would no longer have to be solubilized in a liquid organic solvent, such as by dissolving thymol or other solid ingredient in triglyceride oil, ethanol, or other liquid, before preparation of the emulsion.
• Example 1 The Evaluation and Selection of Emulsifiers
• the emulsifiers evaluated were Glycosperse S-20 KFG (Lonza; Fairlawn, NJ), Polyaldo 10-1-O KFG (Lonza; Fairlawn, NJ), Aldosperse MS-20 KFG (Lonza; Fairlawn, NJ), Polyaldo 10-2-P KFG (Lonza; Fairlawn, NJ), Ryoto sugar ester (S-1570, Mitsubishi-Kagaku Food Corp.; Tokyo, Japan), Precept 8120 (Central Soya; Fort Wayne, IN) and sodium caseinate (Alanate-180, New Zealand Dairy Board; Wellington, New Zealand).
• sucrose ester (S-1570) was identified as a good emulsifier due to the creation of the smallest and most uniformly dispersed oil droplets within the emulsion.
• the emulsion created with the sucrose ester also showed good stability after 24 hours storage at room temperature (about 20 to about 25°C).
• Example 2 Microencapsulation of a Functional Ingredient Containing Some
• sucrose stearate, S-1570 Mitsubishi-Kagaku Food Corp.; Tokyo, Japan
• SiC3 ⁇ 4 AB-D PPG Industries; Pittsburg, PA
• SiC3 ⁇ 4 AB-D PPG Industries; Pittsburg, PA
• the mixture was filtered using a #200 mesh (75 micrometer) screen to produce a cake.
• a separate, clean 4000 ml plastic beaker about 2000 g of D.I.H 2 O and about 2.5 g of Si O 2 AB-D was mixed to create a solution.
• the cake was resuspended in this solution and mixed for about 3 to about 5 minutes.
• the mixture was filtered using a #200 mesh screen to produce a second cake.
• a separate/ clean 4000 ml plastic beaker about 2000 g of D.I.
• the dried filtrate particles were ground using a Magic Bullet MB1001 (Sino link International Trading Co.; Zhejiang, China). Particles between about 75 to about 250 micrometers were separated using #60 and #200 mesh sieves. The moisture content was measured using the OEM Smart System 5 (CEM Corp.; Matthews, NC). To reduce the moisture content to less than about 6 percent, the filtrate was dried in a Uni-Glatt fluid bed dryer (Glatt Air
• the final product had a moisture content of less than about 6 percent.
• the fraction was sifted by passing through a #60 mesh screen and collected on a #200 mesh screen, thereby producing particles having a size of less than about 250 micrometers and greater than about 75 micrometers.
• the composition, payload, and surface oil of the resultant product are illustrated in the table below.
• Example 3 Microencapsulation of a Functional Ingredient Contaixiing Some Esterified Components in an About 75% Shellac / About 25% Zein Matrix at a Pilot Plant Scale
• Example 4 Microencapsulation of a Functional Ingredient Containing Esterified Components with Increased Oil Loading in a Shellac / Zein Matrix Containing Whey Protein as an Emulsifier
• the mixture was homogenized for about 4 minutes at about 15,000 rpm and then at an increased speed of about 20,000 rpm for about 1 additional minute to create a stable emulsion.
• About 3% citric acid solution was titrated into the emulsion using Master Flex pump until the pH reached about 3.8, thereby creating a slurry.
• sucrose stearate, S-1570 Mitsubishi-Kagaku Food Corp.; Tokyo, Japan
• S-1570 Mitsubishi-Kagaku Food Corp.; Tokyo, Japan
• the cake was resuspended in this solution and mixed for about 3 to about 5 minutes.
• the mixture was filtered using #200 mesh (75 micrometer) screen to produce a second filtrate cake.
• #200 mesh (75 micrometer) screen In a separate, clean 4000 ml plastic beaker, about 2000 g of D.I. H 2 O was mixed and pH adjusted to 3.8 +/- about 0.2 by adding about 3.0 percent citric acid solution.
• sucrose stearate was added and mixed until completely dissolved, followed by an addition of about 2.5 g of Si O 2 AB-D.
• the cake was resuspended in this solution and mixed for about 3 to about 5 minutes.
• the mixture was filtered again using #200 mesh (75 micrometer) screen to produce a third filtrate cake.
• the resulting filtrate was pressed using cheese cloth to reduce moisture content
• the filtrate was spread evenly on a large tray on top of a cookie sheet to dry overnight, uncovered and at room temperature (about 20 to about 25 C).
• the resultant particles were ground using a Magic Bullet MB1001 (Sino Link International Trading Co.; Zhejiang, China). The particles sized less than about 250
• micrometers were separated from the rest using a #60 mesh screen.
• the filtrate was dried in a Uni-Glatt fluid bed dryer (Glatt Air Techniques; Ramsey, NJ) at about 40C, checking approximately every 5 minutes.
• the filial product had a moisture content of less than about 6 percent.
• the composition, payload, and surface oil of the resultant product are illustrated in the table below.
• Example 5 Microencapsulation of a Functional Ingredient Containing Some
• the essential oil blend (about 17.4% canola oil, about 6.6% alpha-pinene, about 26.5% para-cymene, about 7.9% linalyl acetate, and about 41.4% thymyl acetate) was added and mixed until a homogenous emulsion was formed with target droplet size of about 4 to about
• Example 6 Non-Esterified Functional Ingredient Microencapsulated in an Alginate / Shellac Matrix
• the solution was atomized, creating moderately small spheres of about 25to about 300 micrometers, into an aqueous hardening bath containing about 2.5% CaCl 2 and about 2.5% citric acid.
• the particles were sieved on a 25 micrometer sieve and dried at about 40°C in the MiniGlatt fluid bed dryer (Glatt Air Techniques; Ramsey, NJ) until the target moisture (about 5 to about 6%) was reached. Particles were sized at less than about 212 micrometers.
• Example 7 Microencapsulation of an Essential Oil Blend Containing
• the essential oil blend (about 18.5% canola oil, about 5.4% alpha-pinene, about 32.3% para-cymene, about 11.2% butyric acid ester of linalool (linalyl butyrate) and about 323% acetic acid ester of thymol (thymyl acetate)) was added and mixed and homogenized until a fine, stable emulsion was formed with target droplet size of about 4 to about 7 micrometers, verified with the Horiba particle size analyzer (Horiba Industries; Irvine, CA). The solution was atomized, creating moderately small spheres between about 25 to about 300 micrometers, into an aqueous hardening bath containing about 2.5% CaCl 2 and about 2.5% citric acid.
• canola oil about 5.4% alpha-pinene, about 32.3% para-cymene, about 11.2% butyric acid ester of linalool (linalyl butyrate) and about 323% acetic acid ester of thymol (
• the particles were then sieved on a 25 micrometer screen to remove the bath solution and then dried at about 40C in the MiniGlatt fluidized bed dryer (Glatt Air Techniques; Ramsey, NJ) until the target moisture (about 5 to about 6%) was reached.
• the particles were sized to less than about 212 micrometers.
• Example 8 Comparison of Payload Retention with Non-Esterified and Esterified Functional Ingredients within an About 75% Alginate / About25% Shellac Matrix
• Example 9 Effect of an Esterified Functional Ingredient on Gastric Release
• This example compares the release of the non-esterified functional ingredient to the esterified functional ingredient during a simulated gastrointestinal study using an in vitro digestion model.
• FIG.3 shows the known properties of the compounds. As shown in the table of FIG.3, the solubility values for the ester compounds (linalyl acetate, linalyl butyrate and thymyl acetate) are significantly lower than the parent compounds (linalool and thymol). In addition, the partition coefficients for the ester compounds are greater than the parent compounds.
• FIGS.4 and 5 show that the release between -0.5 and 0.0 hours, representative of the residence time in the simulated gastric fluid, is greatly reduced for the particles containing some esterified functional ingredient. The reduced rate is most evident when comparing linalool and thymol release from FIG.4 to linalyl acetate and thymyl acetate release from FIG.5.
• This improvement in stability within the model stomach implies increased stability in other low pH systems, such as acidic beverages, and further illustrates the importance of the esters for successful microencapsulation and enteric release of the functional ingredients.
• Example 10 Modulation of the Release from Microencapsulated Particles and the Hydrolysis of the Esterified Components
• Example 9 shows how the selection of various acids for esterifkation can affect the resulting rate of delivery of the parent compounds.
• Example 9 showed the effect on release rate from the particles within a gastric model, as a result of inclusion of some esterified compounds. As evident in FIGS.4 and 5, the gastric release rate was reduced, as well as the release rate from 0-24.5 h, representative of the residence time in the small intestine.
• FIGS.6 and 7 show the release rates of two esters of linalool, linalyl acetate in FIG.6 and linalyl butyrate in FIG. 7 within a digestion model simulating stomach and small intestine conditions and residence times. In addition, the levels of the parent compounds present in the digestion model over time were measured.
• the presence of the parent compound, linalool is a result of hydrolysis of the linalyl acetate.
• the initial release of linalool was about 5% and increases to about 20%, which correlates to about 33% hydrolysis of linalyl acetate to linalool.
• the initial release of linalool was about 2% and increases to about 4%, which correlated to about 5% hydrolysis of the linalyl butyrate to linalool. From those results, it can be seen that by formulating the functional ingredient with varying ratios of linalyl acetate to linalyl butyrate, the resulting level of linalool release through the gastric tract and small intestine can be modulated.
• Example 11 Comparison of Model Beverage Systems with Esterified
• model beverage containing particles comprised of some esterified functional ingredient had a significantly reduced undesirable taste and/ or flavor profile, leading to an improved overall sensory experience.
• a dithymol ester was produced by dissolving about 65 grams of thymol and about 50 milliliters of pyridine in about 400 milliliters of hexane. With the dissolved combination being stirred at room temperature(about 20 to about 25°C), about 50 grams of sebacoyl chloride was added one drop at a time over a period of about 30 to about 45 minutes. After the sebacoyl chloride was added, the mixture was allowed to react overnight at room temperature (about 20 to about 25°C). The next day, the mixture was filtered to remove solid pyridine chloride.
• the clarified filtrate containing dithymol sebacate and hexane was then subjected to further purification by contact with solutions of about IN sodium hydroxide, about IN hydrochloric acid, and then water to remove any unwanted byproducts, unreacted starting materials, and residual pyridine.
• the purified dithymol sebacate in hexane was then dried over anhydrous sodium sulfate overnight to remove traces of water. The sodium sulfate was removed by filtration and the hexane removed by distillation to yield about 80 grams
• Example 13 Preparation of Sodium Thymolate (Sodium Thymoxide)
• sodium thymolate was produced by making a first solution by dissolving about 8 grams of sodium hydroxide in about 25 milliliters of water followed by the addition of about 225 milliliters of absolute ethanol.
• a second solution was prepared by dissolving about 31 grams of thymol in about 100 milliliters of absolute ethanol. With the second solution being stirred at room temperature (about 20 to about 25°C), the first solution was added one drop at a time to the second solution. The combined solution was stirred overnight. The next day, the combined solution was filtered to remove traces of any undissolved reactants or byproducts.
• the absolute ethanol, water, and residual thymol were then removed by placing the filtered combined solution under a vacuum overnight at a temperature of about 40°C.
• the dried sodium thymolate was then removed from the flask to yield about 32 grams (approximately 93% yield) of product.
• the dried sodium thymolate could be further purified to remove traces of residual thymol by admixing the sodium thymolate with hexane (about 2 milliliters of hexane per 1 gram of sodium thymolate), filtering to remove the hexane, and drying the further purified sodium thymolate under vacuum.
• compositions and methods have been particularly described with specific reference to particular process and product embodiments, it will be appreciated that various alterations, modifications, and adaptations may be based on the present disclosure, and are intended to be within the spirit of this disclosure.

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