WO2023158844A1

WO2023158844A1 - Heat-treated powdered nutritional compositions and processes for maintaining (2s)-hesperidin

Info

Publication number: WO2023158844A1
Application number: PCT/US2023/013403
Authority: WO
Inventors: Ai Mey Chuah; Ding Yi; Sarah STEINBRUNNER; Rockendra GUPTA; Quang Son PHAM; Suzette Pereira; Ricardo Rueda Cabrera
Original assignee: Abbott Laboratories
Priority date: 2022-02-21
Filing date: 2023-02-20
Publication date: 2023-08-24

Abstract

A heat-treated, powdered nutritional composition comprises protein, fat, carbohydrate, and about 0.001 to about 5 wt % hesperidin, based on the weight of the powdered nutritional composition, wherein the weight ratio of (2S)-hesperidin to (2R)-hesperidin in the powdered nutritional composition is at least about 4:1. A process for manufacturing a heat-treated, powdered nutritional composition comprising hesperidin comprises providing an emulsified liquid nutritional composition comprising protein, fat, carbohydrate, and hesperidin, heat treating the emulsified liquid nutritional composition at a temperature of at least about 70ºC and not greater than about 105ºC for about 1 to about 30 seconds, and spray-drying the heat-treated liquid nutritional composition to form the powdered nutritional composition.

Description

HEAT-TREATED POWDERED NUTRITIONAL COMPOSITIONS AND PROCESSES FOR MAINTAINING (2S)-HESPERIDIN

FIELD OF THE INVENTION

[0001] The present invention is directed to heat-treated, powdered nutritional compositions comprising protein, fat, carbohydrate, and hesperidin, and having a high weight ratio of (2S)- hesperidin to (2R)-hesperidin. The present invention is also directed to processes for preparing nutritional compositions wherein the (2S) form of hesperidin is substantially maintained and significant conversion to the (2R) form of hesperidin is avoided.

BACKGROUND OF THE INVENTION

[0002] Hesperidin (IUPAC name, (2S)-3',5-Dihydroxy-4'-methoxy-7-[a-L-rhamnopyranosyl- (1— >6)-[3-D-glucopyranosyloxy]flavan-4-one; also known as hesperetin-7-O-rutinoside) is the major flavonoid present in sweet oranges (Citrus sinensis) and orange juice, but is also found in lower levels in other citrus fruits including lemon, lime, grapefruit, mandarin, other oranges, and some herbs. Various studies have demonstrated therapeutic effects of hesperidin and its metabolites, including anti-inflammatory properties, antioxidant properties, inhibition of fat accumulation, improvements in homeostasis and insulin sensitivity, improvements in muscle energy production and/or muscle strength, and reducing muscle loss.

[0003] Within the family of flavonoids, hesperidin and other flavanones present a unique structural feature known as chirality, which distinguishes them from other classes of flavonoids. The flavanones have a chemical structure based on a C6-C3-C6 configuration consisting of two aromatic rings joined by a three-carbon link. Almost all flavanones have one chiral carbon atom in position C2 that can generate diastereomers. Hesperidin therefore exists in 2S and 2R configurations. (2S)-Hesperidin is naturally predominant in citrus fruits, and in fresh sweet orange juice is present in an S:R ratio (both molar and weight as the diastereomers have the same molecular weight) of at least about 92:8. Thus, (2S)-hesperidin is considered the ‘natural’ form of hesperidin, which then gets converted to the aglycone form, S(-)-hesperetin, upon metabolism by gut microbiota. There appear to be some differences in the metabolism, transport and bioactivity of the hesperetin enantiomers, and therefore it is desirable to maintain as much of the natural (2S)-hesperidin in processed nutritional product formulations as possible. [0004] It is known that excessive processing can cause transformation of (2S)-hesperidin to (2R)-hesperidin. Although the exact factors leading to the conversion of (2S)-hesperidin to (2R)- hesperidin are not well established, minimizing processing of the products containing (2S)- hesperidin is one of the key steps in preserving (2S)-hesperidin. For example, it is known that levels of (2S)-hesperidin are higher in fresh squeezed orange juice and organic orange juice as compared with conventionally processed orange juice. However, to prepare a long-term (at least several month) shelf-stable nutritional product, the product needs to go through numerous processing steps, including high heat treatments which result in loss of (2S)-hesperidin by conversion to (2R)-hesperidin. Conversion of (2S)-hesperidin to (2R)-hesperidin has also been reported to occur due to spray drying, for example, when forming a powdered product. Accordingly, improvements are desired in methods of processing citrus flavonoid-containing nutritional formulations to preserve the (2S)-hesperidin content when forming shelf stable, heat- treated nutritional compositions.

SUMMARY OF THE INVENTION

[0005] It is therefore an object of the invention to provide heat-treated nutritional compositions having a high weight ratio of (2S)-hesperidin to (2R)-hesperidin and processes for preparing such nutritional compositions wherein the (2S) form of hesperidin is substantially maintained and significant conversion to the (2R) form of hesperidin is avoided.

[0006] In one embodiment, the invention is directed to a heat-treated, powdered nutritional composition which comprises protein, fat, carbohydrate, and about 0.001 to about 5 wt % hesperidin, based on the weight of the powdered nutritional composition. The weight ratio of (2S)-hesperidin to (2R)-hesperidin in the powdered nutritional composition is at least about 4:1. [0007] In another embodiment, the invention is directed to a process for manufacturing a heat-treated, powdered nutritional composition comprising hesperidin. The process comprises providing an emulsified liquid nutritional composition comprising protein, fat, carbohydrate, and hesperidin, heat treating the emulsified liquid nutritional composition at a temperature of at least about 70°C and not greater than about 105°C for about 1 to about 30 seconds, and spray-drying the heat-treated liquid nutritional composition to form the powdered nutritional composition. The weight ratio of (2S)-hesperidin to (2R)-hesperidin in the powdered nutritional composition is at least about 4:1.

[0008] The compositions and processes of the invention are advantageous in providing shelf stable nutritional compositions in powdered form having a relatively high content of (2S)- hesperidin relative to (2R)-hesperidin content.

DETAILED DESCRIPTION

[0009] While the general inventive concepts are susceptible of embodiment in many different forms, described herein in detail are specific embodiments of the invention, with the understanding that the present disclosure is to be considered as an exemplification of the principles of the general inventive concepts. Accordingly, the general inventive concepts are not intended to be limited to the specific embodiments illustrated and described herein.

[00010] All percentages, parts and ratios as used herein, are by weight of the total composition, unless otherwise specified. All such weights as they pertain to listed ingredients are based on the active level and, therefore, do not include solvents or byproducts that may be included in commercially available materials, unless otherwise specified.

[00011] The terminology as set forth herein is for description of the embodiments only and should not be construed as limiting the disclosure as a whole. Unless otherwise specified, “a,” “an,” “the,” and “at least one” are used interchangeably. Furthermore, as used in the description and the appended claims, the singular forms “a,” “an,” and “the” are inclusive of their plural forms, unless the context clearly indicates otherwise.

[00012] Throughout this specification, when a range of values is defined with respect to a particular characteristic of the present invention, the present invention relates to and explicitly incorporates every specific subrange therein. Additionally, throughout this specification, when a group of substances is defined with respect to a particular characteristic of the present invention, the present invention relates to and explicitly incorporates every specific subgroup therein. Any specified range or group is to be understood as a shorthand way of referring to every member of a range or group individually as well as every possible subrange or subgroup encompassed therein.

[00013] The methods and nutritional compositions described herein may comprise, consist of, or consist essentially of the essential steps and elements, respectively, as described herein, as well as any additional or optional steps and elements, respectively, described herein. Any combination of method or process steps as used herein may be performed in any order, unless otherwise specified or clearly implied to the contrary by the context in which the referenced combination is made.

[00014] The various embodiments of the nutritional compositions of the invention may also be substantially free of any optional or selected ingredient or feature described herein, provided that the remaining nutritional composition still contains all of the required ingredients or features as described herein. In this context, and unless otherwise specified, the term “substantially free” means that the selected nutritional composition contains less than a functional amount of the optional ingredient, typically less than 1%, including less than 0.5%, including less than 0.1%, and also including zero percent, by weight, of such optional or selected essential ingredient.

[00015] Unless otherwise indicated herein, all exemplary embodiments, sub-embodiments, specific embodiments and optional embodiments are respective exemplary embodiments, sub-embodiments, specific embodiments and optional embodiments to all embodiments described herein.

[00016] As noted above, hesperidin exists as two different enantiomers, the (2S) enantiomer and the (2R) enantiomer:

[00017] The heat-treated nutritional compositions of the invention are in powder form and contain a weight ratio of the (2S) enantiomer to the (2R) enantiomer of at least 4:1. In a more specific embodiment of the powdered nutritional compositions, the weight ratio of the (2S)- hesperidin enantiomer to the (2R) enantiomer is at least 5:1. In yet more specific embodiments of the powdered nutritional compositions, the weight ratio of the (2S)-hesperidin enantiomer to the (2R)-hesperidin enantiomer is at least 6:1. As discussed in detail below, the relatively high ratio of the (2S)-hesperidin enantiomer to the (2R)-hesperidin enantiomer is maintained by carefully controlling the heat treatment which provides shelf stability in the defined nutritional compositions.

[00018] More specifically, the powdered nutritional compositions comprise protein, fat, carbohydrate, and about 0.001 to about 5 wt % hesperidin, based on the weight of the powdered nutritional composition. In more specific embodiments, the compositions comprise from about 0.01 to about 5 wt %, from about 0.01 to about 3 wt %, or from about 0.01 to about 1 wt % hesperidin, based on the weight of the powdered nutritional composition. The hesperidin may be included in the form of an extract, a purified natural component, or a synthetically- produced ingredient.

[00019] The protein which is contained in the nutritional composition may be any one or more proteins known for use in nutritional compositions. A wide variety of sources and types of protein can be used in the nutritional compositions. For example, the source of protein may include, but is not limited to, intact, hydrolyzed, and partially hydrolyzed protein, which may be derived from any suitable source such as milk (e.g., casein, whey), animal (e.g., meat, fish), cereal (e.g., rice, brown rice, oat, barley, etc.), vegetable (e.g., soy, corn, pea, yellow pea, fava bean, chickpea, canola, potato, mung, ancient grains such as quinoa, amaranth, chia, hemp, flax seed, etc.), nuts (e.g., almond and cashew), and combinations of two or more thereof. The protein may also include one or a mixture of naturally occurring or synthetic amino acids (often described as free amino acids) and/or their metabolites, known for use in nutritional products, alone or in combination with the intact, hydrolyzed, and/or partially hydrolyzed proteins described herein.

[00020] More specific examples of sources of protein which are suitable for use in the exemplary nutritional compositions described herein include, but are not limited to, whole egg powder, egg yolk powder, egg white powder, whey protein (including, but not limited to, whey protein components such as a-lactalbumin and p-lactoglobulin), whey protein concentrates, whey protein isolates, whey protein hydrolysates, acid caseins, casein protein isolates, sodium caseinates, calcium caseinates, potassium caseinates, casein hydrolysates, milk protein concentrates, milk protein isolates, milk protein hydrolysates, nonfat dry milk, condensed skim milk, whole cow’s milk, partially or completely defatted milk, coconut milk, soy protein concentrates, soy protein isolates, soy protein hydrolysates, pea protein concentrates, pea protein isolates, pea protein hydrolysates, rice protein concentrate, rice protein isolate, rice protein hydrolysate, barley rice protein, fava bean protein concentrate, fava bean protein isolate, fava bean protein hydrolysate, collagen proteins, collagen protein isolates, meat proteins such as beef protein isolate and/or chicken protein isolate, potato proteins, chickpea proteins, canola proteins, mung proteins, quinoa proteins, amaranth proteins, chia proteins, hemp proteins, flax seed proteins, almond proteins, cashew proteins, earthworm proteins, insect proteins, and combinations of two or more thereof. The nutritional compositions can include any individual source of protein or a combination of any two or more sources of protein. In specific embodiments, the nutritional compositions comprise at least one milk protein, or at least one plant protein, or both at least one milk protein and at least one plant protein.

[00021] The amount of the protein in the nutritional compositions can vary considerably depending upon, for example, the specific dietary needs of the intended user. In specific embodiments, the powdered nutritional compositions comprise from about 5 wt % to about 30 wt %, about 5 wt % to about 25 wt %, about 5 wt % to about 20 wt %, about 10 wt % to about 30 wt %, about 10 wt % to about 25 wt %, or about 10 wt % to about 20 wt % of protein.

[00022] The inventive nutritional compositions also include fat. The term “fat” as used herein, unless otherwise specified, refers to lipids, fats, oils, and combinations of two or more thereof. Sources of fat suitable for use in the nutritional composition include, but are not limited to, algal oil, canola oil, flaxseed oil, borage oil, safflower oil, high oleic safflower oil, high gamma-linolenic acid (GLA) safflower oil, corn oil, soy oil, sunflower oil, high oleic sunflower oil, cottonseed oil, coconut oil, fractionated coconut oil, medium chain triglycerides (MCT) oil, palm oil, palm kernel oil, palm olein, lecithin, and long chain polyunsaturated fatty acids such as docosahexanoic acid (DHA), arachidonic acid (ARA), docosapentaenoic acid (DPA), eicosapentaenoic acid (EPA), and combinations of two or more thereof. The nutritional compositions can include any individual source of fat or a combination of two or more sources of fat. In specific embodiments, the fat source comprises corn oil, canola oil, sunflower oil, high oleic sunflower oil, or a combination of two or more thereof.

[00023] In specific embodiments, the nutritional compositions comprise about 5 wt % to about

25 wt % of fat. In more specific embodiments, the compositions comprise about 5 wt % to about 20 wt %, about 5 wt % to about 15 wt %, about 10 wt % to about 25 wt %, about 10 wt % to about 20 wt %, or about 10 wt % to about 15 wt %, of fat.

[00024] Sources of carbohydrates suitable for use in the nutritional compositions may be simple or complex, or variations, or combinations thereof. Various sources of carbohydrate may be used so long as the source is suitable for use in a nutritional composition and is otherwise compatible with any other selected ingredients or features present in the nutritional composition. Non-limiting examples of sources of carbohydrates suitable for use in the nutritional compositions include maltodextrin, hydrolyzed or modified starch, hydrolyzed or modified cornstarch, glucose polymers such as polydextrose and dextrins, corn syrup, corn syrup solids, rice-derived carbohydrates such as rice maltodextrin, brown rice mild powder and brown rice syrup, sucrose, glucose, fructose, lactose, high fructose corn syrup, honey, sugar alcohols (e.g., maltitol, erythritol, sorbitol), isomaltulose, sucromalt, pullulan, potato starch, corn starch, fructooligosaccharides, galactooligosaccharides, oat fiber, soy fiber, gum arabic, sodium carboxymethylcellulose, methylcellulose, guar gum, gellan gum, locust bean gum, konjac flour, hydroxypropyl methylcellulose, tragacanth gum, karaya gum, gum acacia, chitosan, arabinoglactins, glucomannan, xanthan gum, alginate, pectin, low methoxy pectin, high methoxy pectin, cereal beta-glucans, carrageenan, psyllium, FibersolTM, fruit puree, vegetable puree, isomalto-oligosaccharides, monosaccharides, disaccharides, human milk oligosaccharides (HMDs), tapioca-derived carbohydrates, inulin, other digestion-resistant starches, and artificial sweeteners, and combinations of two or more thereof. The nutritional compositions may include any individual source of carbohydrate or a combination of two or more sources of carbohydrate. In specific embodiments, the carbohydrate comprises corn syrup, corn syrup solids, corn maltodextrin, fructooligosaccharide, sucrose, or a combination of two or more thereof.

[00025] In specific embodiments, the powdered nutritional compositions comprise from about 40 wt % to about 75 wt % of carbohydrate. In more specific embodiments, carbohydrate is present in an amount from about 40 wt % to about 70 wt % of the powdered nutritional composition, including about 40 wt % to about 65 wt %, about 40 wt % to about 60 wt %, about 50 wt % to about 75 wt %, about 50 wt % to about 70 wt %, or about 50 wt % to about 65 wt %. [00026] The relative amounts of the protein, fat and carbohydrate in the nutritional compositions can vary considerably depending upon, for example, the specific dietary needs of the intended user. In a specific embodiment, the powdered nutritional compositions comprise about 5 wt % to about 30 wt % protein, about 5 wt % to about 25 wt % fat, and about 40 wt % to about 75 wt % carbohydrate. In a more specific embodiment, the powdered nutritional compositions comprise about 10 wt % to about 25 wt % protein, about 5 wt % to about 20 wt % fat, and about 50 wt % to about 75 wt % carbohydrate. In another specific embodiment, the powdered nutritional compositions comprise about 10 wt % to about 20 wt % protein, about 10 wt % to about 20 wt % fat, and about 50 wt % to about 70 wt % carbohydrate.

[00027] In specific embodiments, the powdered nutritional composition has a neutral pH, i.e., a pH of from about 6 to about 8 or, more specifically, from about 6 to about 7.5. In more specific embodiments, the nutritional composition has a pH of from about 6.5 to about 7.2 or, more specifically, from about 6.8 to about 7.2. The pH of the powdered nutritional composition is determined by reconstituting 55 g the powdered nutritional composition with 8 fluid ounces (237 ml) water.

[00028] The nutritional composition may further comprise one or more additional components that may modify the physical, chemical, aesthetic, or processing characteristics of the nutritional composition or serve as additional nutritional components. Non-limiting examples of additional components include preservatives, emulsifying agents (e.g., lecithin), buffers, sweeteners including artificial sweeteners (e.g., saccharine, aspartame, acesulfame K, sucralose), colorants, flavorants, thickening agents, stabilizers, and so forth.

[00029] Additionally, the nutritional composition may further include vitamins or related nutrients, non-limiting examples of which include vitamin A, vitamin B12, vitamin C, vitamin D, vitamin K, thiamine, riboflavin, pyridoxine, niacin, folic acid, pantothenic acid, biotin, choline, inositol, salts and derivatives thereof, and combinations of two or more thereof. Water soluble vitamins may be added in the form of a water-soluble vitamin (WSV) premix and/or oil-soluble vitamins may be added in one or more oil carriers as desired.

[00030] In additional embodiments, the nutritional composition further comprises p-hydroxy-p- methylbutyrate (HMB). Any suitable source of HMB may be employed, including the free acid, a salt, including hydrated or anhydrous salts, an ester, a lactone, or other product form that otherwise provides a bioavailable form of HMB when administered. Non-limiting examples of suitable salts of HMB for use herein include HMB salts, hydrated or anhydrous, of sodium, potassium, magnesium, chromium, calcium, or other non-toxic salt form. In a more specific embodiment, the HMB is in the form of calcium HMB, or, more specifically, calcium HMB monohydrate. In a specific embodiment, the powdered nutritional compositions comprise from about 0.1 wt % to about 3 wt % HMB.

[00031] In additional embodiments, the nutritional composition may further include one or more minerals, non-limiting examples of which include calcium, phosphorus, magnesium, zinc, manganese, sodium, potassium, molybdenum, chromium, chloride, and combinations of two or more thereof.

[00032] In additional embodiments, the nutritional composition may further include one or more probiotics. The term “probiotic” as used herein refers to a microorganism such as a bacteria or yeast that survives the digestive process to confer a health benefit to the subject. Examples of probiotics that can be included in the nutritional compositions, either alone or in combination, include, but are not limited to, Bifidobacterium (8.), such as B. breve, B. infantis, B. lactis, B. bifidum, B. longum, and 8. ani mails, Lactobacillus (L), such as L. rhamnosus, L. acidophilus, L fermentum, and L. reuteri, Streptococcus thermophilus, Akkermansia, Bacteroides, Enterococcus, Eubacterium, Fecalibacterium, Roseburia, and/or Saccharomyces. [00033] The nutritional compositions may be formed using any techniques known in the art for combining the ingredients. In one embodiment, emulsified liquid nutritional compositions may be formed by (a) preparing an aqueous solution comprising protein and carbohydrate and, optionally, other water-soluble and/or water-compatible components; (b) preparing an oil blend comprising fat and oil-soluble components; and (c) mixing the aqueous solution and the oil blend together to form an emulsified liquid nutritional composition. The hesperidin may be added at any time as desired in the process, for example, to the aqueous solution before or after protein addition, or to the emulsified blend prior to heat treatment. Homogenization may be conducted to form a homogeneous emulsified product before or after heat treatment. In a specific embodiment homogenization is conducted after heat treatment.

[00034] The resulting emulsified liquid nutritional compositions are subjected to a heat treatment which provides sterilization sufficient to maintain microbiological stability, /.e., shelf stability, of the compositions over a desired shelf-life, for example, at least 2 months, at least 3 months, at least 4 months, at least 5 months, or at least 6 months. Importantly, the emulsified liquid nutritional composition is heat treated at a temperature of at least about 70°C and not greater than about 105°C for about 1 to about 30 seconds. In more specific embodiments, the emulsified liquid nutritional composition is heat treated at a temperature of at least about 75°C, or at least about 80°C, and not greater than about 105°C for about 1 to about 30 seconds. In further specific embodiments, the described heat treatment is conducted for about 5 to about 30 seconds, about 10 to about 30 seconds, about 15 to about 30 seconds, about 5 to about 25 seconds, about 10 to about 25 seconds, or about 15 to about 25 seconds. Surprisingly, a heat treatment as described provides sufficient sterilization to maintain microbiological stability of the compositions over a desired shelf-life, while avoiding significant conversion of (2S)-hesperidin to (2R)-hesperidin. Higher temperature heat treatment substantially increases undesirable conversion of (2S)-hesperidin to (2R)-hesperidin. On the other hand, and further surprising, the thus heat-treated liquid nutritional compositions can be spray dried to form the desired powdered nutritional composition products without significant conversion of (2S)-hesperidin to

(2R)-hesperidin in the resulting spray-dried powder. Therefore, the inventive process further comprises spray drying the heat-treated liquid nutritional product to form a powdered nutritional composition. In specific embodiments, the spray-drying is conducted with inlet air at a temperature of from about 180°C to about 200°C, or, more specifically, with inlet air at a temperature of about 190°C.

[00035] The powdered nutritional composition may be administered to a subject in powder form, for example by sprinkling on a food product, for example, cereal, toast, etc., or in a beverage, for example, coffee, tea, etc. In an alternate, and preferred, embodiment, the powdered nutritional composition is reconstituted to liquid form by mixing with water. Suitably, from 50 to 60 grams of powdered nutritional product as described herein can be mixed with 8 fluid ounces (237 ml) water to form a reconstituted liquid. In additional embodiments, such reconstituted liquids comprise hesperidin in an amount of about 50 to about 1000 mg per 237 ml serving, about 50 to about 800 mg per 237 ml serving, about 50 to about 500 mg per 237 ml serving, about 50 to about 300 mg per 237 ml serving, about 100 to about 300 mg per 237 ml serving, or about 100 to about 500 mg per 237 ml serving.

[00036] Various aspects of the powdered nutritional compositions and processes of the invention are demonstrated in the following Example.

EXAMPLE

[00037] Emulsified liquid nutritional compositions were prepared by (a) preparing an aqueous solution comprising protein and carbohydrate; (b) preparing an oil blend comprising fat and oilsoluble components; and (c) mixing the aqueous solution and the oil blend together to form an emulsified liquid nutritional composition. Water soluble vitamins and flavors were added and the total solids were adjusted. The components were employed in amounts effective to provide a powdered nutritional composition as described in Table 1. The liquid compositions had a pH of from about 6.5 to about 7.2

[00038] Table 1 : Final Powdered Nutritional Composition

[00039] Heat treatment of individual samples of the emulsified liquid composition was conducted at temperatures as indicated in Table 2. After heat treatment, the heat-treated liquid samples were dried. In one embodiment, the heat-treated liquid was spray dried using air heated to an inlet temperature of 190°C to form powdered compositions. The amount of (2S)- hesperidin in the various heat-treated liquid samples and spray-dried powdered products was measured using high pressure liquid chromatography (HPLC) with the following sample preparation and HPLC parameters:

[00040] Sample preparation: combine 2 ml sample (0.2 g for finished powder and 0.5 g for heat-treated liquid sample) in total 10 ml MeOH : DMSO (1 :1); mix well; centrifuge 2 ml, 16000 x g for 20 min; combine 1 ml supernatant and 1 ml MeOH 0.5% acetic acid; mix well; centrifuge, 16000 x g for 30 min; and transfer supernatant to HPLC vial.

[00041] HPLC Column: Chiralpak® AD-H, 250 mm x 4.6 mm, Amylose tris-(3,5- di methyl phenylcarbamate), 5pm.

Conditions:

Temperature: room temperature

Mobile phase: n-Heptane/2-Propanol/Trifluoracetic acid (500:500:1) Flow: 1 mL/min Pressure limitation: < 300 bar Injection volume: 5 pL Detection: 284 nm

Run Time: 40 minutes

[00042] The amounts of (2S)-hesperidin in the various samples is indicated in Table 2 as a percentage of the original hesperidin content.

[00043] Table 2: (2S)-Hesperidin Content

*Typical conditions for retort sterilization. Total cook time including heating and cooling cycles to achieve the desired cumulative lethality for a commercially sterile product is 43 minutes.

**190°C is the temperature of the inlet spray drying air.

[00044] As is evident from Table 2, the heat treatments in a range of 80 to 105°C for between 1 and 30 seconds surprisingly maintained a high content of (2S)-hesperidin in both the heat- treated liquid, in the dried powder, and in the spray-dried powdered product. On the other hand, even a short, 5 second heat treatment at 140°C caused a 10% loss of the (2S)-hesperidin in the liquid product. Additionally, heat treatment at 127°C for 5 minutes, 15 seconds, caused a 45% loss of (2S)-hesperidin in the liquid product.

[00045] While the present application has been illustrated by the description of embodiments thereof, and while the embodiments have been described in considerable detail, such descriptions are not intended to restrict or in any way limit the scope of the appended claims to such detail. Additional advantages and modifications will readily appear to those skilled in the art. Therefore, the invention, in its broader aspects, is not limited to the specific details, the representative methods or compositions, or illustrative examples shown and described.

Accordingly, departures may be made from such details without departing from the spirit or scope of the general inventive concept.

Claims

Claims What is claimed is:

1. A heat-treated, powdered nutritional composition, comprising protein, fat, carbohydrate, and about 0.001 to about 5 wt % hesperidin, based on the weight of the powdered nutritional composition, wherein the weight ratio of (2S)-hesperidin to (2R)-hesperidin in the powdered nutritional composition is at least about 4:1 .

2. The heat-treated, powdered nutritional composition of claim 1 , comprising from about 0.01 to about 5 wt %, from about 0.01 to about 3 wt %, or from about 0.01 to about 1 wt % hesperidin, based on the weight of the powdered nutritional composition.

3. The heat-treated, powdered nutritional composition of claim 1 or 2, wherein a reconstituted liquid formed by mixing 55 g of the powdered nutritional composition with 8 fluid ounces of water has a pH of from about 6 to about 7.5, or from about 6.5 to about 7.2.

4. The heat-treated, powdered nutritional composition of any one of claims 1-3, wherein the weight ratio of (2S)-hesperidin to (2R)-hesperidin in the powdered nutritional composition is at least about 5:1.

5. The heat-treated, powdered nutritional composition of any one of claims 1-4, wherein the protein comprises milk protein, plant protein or a combination thereof, the fat comprises corn oil, canola oil, sunflower oil, high oleic sunflower oil, or a combination of two or more thereof, and the carbohydrate comprises corn syrup, corn syrup solids, corn maltodextrin, fructooligosaccharide, sucrose, or a combination of two or more thereof.

6. The heat-treated, powdered nutritional composition of any one of claims 1-5, comprising from about 5 wt % to about 30 wt % protein, from about 5 wt % to about 25 wt % fat, and from about 40 wt % to about 75 wt % carbohydrate, based on the weight of the nutritional composition.

7. The heat-treated, powdered nutritional composition of any one of claims 1-6, further comprising from about 0.1 wt % to about 3 wt % p-hydroxy-p-methylbutyrate.

8. The heat-treated, powdered nutritional composition of any one of claims 1-6, further comprising one or more of vitamin A, vitamin B12, vitamin C, vitamin D, vitamin K, thiamine, riboflavin, pyridoxine, niacin, folic acid, pantothenic acid, biotin, choline, and inositol.

9. A process for manufacturing a heat-treated, powdered nutritional composition comprising hesperidin, the process comprising: providing an emulsified liquid nutritional composition comprising protein, fat, carbohydrate, and hesperidin; heat treating the emulsified liquid nutritional composition at a temperature of at least about 70°C, at least about 75°C, or at least about 80°C, and not greater than about 105°C for about 1 to about 30 seconds; and spray-drying the heat-treated liquid nutritional composition to form the powdered nutritional composition, wherein the weight ratio of (2S)-hesperidin to (2R)-hesperidin in the powdered nutritional composition is at least about 4:1 .

10. The process of claim 9, wherein the emulsified liquid nutritional composition is heat- treated at a temperature of at least about 75°C and not greater than about 105°C for about 5 to about 25 seconds.

11. The process of claim 9 or 10, wherein the spray-drying is conducted with air at a temperature of from about 180°C to about 200°C.

12. The process of any one of claims 9-11 , wherein the weight ratio of (2S)-hesperidin to (2R)-hesperidin in the powdered nutritional composition is at least about 5:1.

13. The process of any one of claims 9-12, wherein the emulsified liquid nutritional composition comprises from about 0.001 to about 5 wt % hesperidin, based on the weight of the emulsified liquid nutritional composition.

14. The process of any one of claims 9-13, wherein the powdered nutritional composition comprises from about 0.01 to about 5 wt %, from about 0.01 to about 3 wt %, or from about 0.01 to about 1 wt % hesperidin, based on the weight of the powdered nutritional composition.

15. The process of any one of claims 9-14, wherein the emulsified liquid nutritional composition has a pH of from about 6 to about 7.5, or from about 6.5 to about 7.2.

16. The process of any one of claims 9-15, wherein the protein comprises milk protein, plant protein or a combination thereof, the fat comprises corn oil, canola oil, sunflower oil, high oleic sunflower oil, or a combination of two or more thereof, and the carbohydrate comprises corn syrup, corn syrup solids, corn maltodextrin, fructooligosaccharide, sucrose, or a combination of two or more thereof.

17. The process of any one of claims 9-16, wherein the powdered nutritional composition comprises from about 5 wt % to about 30 wt % protein, from about 5 wt % to about 25 wt % fat, and from about 40 wt % to about 75 wt % carbohydrate, based on the weight of the nutritional composition.

18. The process of any one of claims 9-17, wherein the powdered nutritional composition further comprises from about 0.1 to about 3 wt % p-hydroxy-p-methylbutyrate.

19. The process of any one of claims 9-18, wherein the powdered nutritional composition further comprises one or more of vitamin A, vitamin B12, vitamin C, vitamin D, vitamin K, thiamine, riboflavin, pyridoxine, niacin, folic acid, pantothenic acid, biotin, choline, and inositol.