Dairy product and process

Abstract

To provide heat-treated shelf-stable liquid nutritional compositions containing whey protein and non-whey protein, and a method for producing and using the compositions.SOLUTION: These compositions contain a pH of about 6.0 to about 8.0 and a total protein content of at least about 6 grams per 100 mL of the compositions. Whey protein contains or is provided by ingredients containing heat-denaturable protein of which at least about 55% is present in a denatured state, and non-whey protein contains or consists of casein, or one or more non-dairy proteins, or casein and one or more non-dairy proteins.SELECTED DRAWING: Figure 1

Description

Technical Field

[0001] The present invention relates to high-protein liquid nutritional compositions, and methods for preparing and using them.

Background Art

[0002] For the elderly, or convalescents, or other patients who cannot obtain the necessary nutrients by eating normal food, or who cannot eat by themselves, or who need assistance during meals, there are various special foods (meal replacements, nutritional supplements, and / or dietary supplements). Common terms used to classify these foods include "medical foods", "enteral foods", "enteral nutrition", "medical liquids", "oral nutritional supplements", etc., and are used generically to refer to foods consumed under the supervision of medical professionals. In some jurisdictions, there are legal definitions for medical foods / enteral nutrition. In the United States, the term "medical food" as defined in section 5(b) of the Orphan Drug Act (21 U.S.C. 360ee(b)(3)) is "a food which is formulated to be consumed or administered enterally under the supervision of a physician and which is intended for the specific dietary management of a disease or condition for which distinctive nutritional requirements, based on recognized scientific principles, have been established by medical evaluation". In some jurisdictions, such foods are only available to the general public with a prescription, while in other jurisdictions, these can be obtained directly over the counter (OTC).

[0003] Enteral formulations are taken both orally and via a tube. Oral intake is useful when nutritional supplements are needed and both the digestive tract and the patient are able to take them. Patients who need nutritional agents but are unable to take nutrition orally require tube feeding.

[0004] All of these foods have very strict requirements. These include sterility and long shelf-life stability, high calorie density, i.e., they require a high degree of heat treatment to provide a high concentration dose of nutrients, but at the same time also require a low viscosity so that they can be easily administered to patients and consumed easily.

[0005] Liquid nutritional foods are also used as meal replacements by healthy subjects or when quickly consumable foods are needed. Liquid nutritional foods are generally suitable for use by children, the elderly, or athletes, and for these consumers, product sensory characteristics such as, for example, viscosity, mouthfeel, odor, and color are very important.

[0006] Liquid nutritional foods often have a high calorie density in that they contain nutrients such as fat, protein, carbohydrates, etc. at levels and in combinations that achieve a calorific value of at least 0.5 kcal / g or kcal / mL. In the group of medical foods or enteral foods, calorie densities of up to 3 kcal / g or more are known. Achieving such a high calorie density is difficult with a low viscosity and sufficient protein. Hydrolyzed proteins can be used to achieve a low viscosity. However, hydrolyzed proteins significantly reduce taste acceptability, thus reducing the voluntary intake of nutritional compositions by patient groups.

[0007] Existing high-protein, high-energy liquid nutritional compositions containing more than 10 grams of protein per 100 mL of composition are mainly due to casein as the main source of protein. High-protein liquid nutritional compositions containing casein are known to cause coagulation in the upper digestive tract, resulting in delayed gastric emptying, discomfort, and a reduced food intake.

[0008] Generally, the coagulation of milk proteins refers to gel formation, where casein micelles are destabilized by acids and / or enzymes, the micelles aggregate to form a network, thereby partially immobilizing water and capturing fat globules in the newly formed matrix. Ye reported that milk proteins, more specifically micellar or non-micellar casein or caseinate, form clots in the acidic gastric environment, thus being retained longer in the stomach and delaying the delivery of amino acids to the upper intestinal lumen (Ye et al., 2016. Food Hydrocolloids, 52:478 - 486). Therefore, nutritional compositions containing micellar and / or non-micellar casein and / or caseinate and / or milk proteins or mixtures thereof as the main protein source may cause a delay in gastric emptying, thereby potentially causing discomfort in the upper gastrointestinal tract.

[0009] Whey protein is recognized not only as a suitable protein source for treating people suffering from diseases or illnesses, or as a result of the treatment of diseases or illnesses such as cachexia and sarcopenia, but also as a valuable nutritional source for healthy people such as athletes and active elderly individuals. Whey protein maintains solubility and quickly passes through the stomach, thus accelerating the delivery of amino acids to the circulatory system. However, the high heat treatment (i.e., retort treatment or UHT) applied to liquid nutritional compositions to ensure product safety and extended shelf life results in unacceptable gelation and aggregation of compositions containing a high whey protein content. Such gelation poses a risk of widespread fouling and blocking in production plants, particularly UHT heating devices.

[0010] In the art, there is a need for heat-treated, storage-stable, high-protein liquid nutritional compositions with neutral pH and low viscosity that do not readily coagulate in the upper digestive tract.

[0011] The object of the present invention is to provide an improved or alternative liquid nutritional composition that is capable of fulfilling this need and / or overcoming the aforementioned difficulties to some extent, or at least to provide a useful option for the general population. Summary of the Invention

[0012] In one aspect, the present invention is a heat - treated storage - stable liquid nutritional composition having a pH of from about 6.0 to about 8.0, comprising a total protein content of at least about 6 g per 100 mL of the composition, the total protein content being a) whey protein, comprising or provided by a raw material containing a heat - denaturable protein with at least about 55% present in a denatured state, or b) non - whey protein, comprising or consisting of casein, or one or more non - milk proteins, or casein and one or more non - milk proteins,

[0013] In another aspect, the present invention is a heat - treated storage - stable liquid nutritional composition having a pH of from about 6.0 to about 8.0, comprising a total protein content of at least about 6 g per 100 mL of the composition, the total protein content being a) whey protein, comprising or provided by a raw material containing a heat - denaturable protein with at least about 55% present in a denatured state, or b) non - whey protein, comprising or consisting of casein, or one or more non - milk proteins, or casein and one or more non - milk proteins, wherein the whey protein has a degree of hydrolysis of less than about 4%, and the whey protein and non - whey protein are present in a weight ratio of at least about 35:65, preferably from about 35:65 to about 80:20.

[0014] In another aspect, the present invention is a heat - treated storage - stable liquid nutritional composition having a pH of from about 6.0 to about 8.0, containing at least about 6 g of total protein per 100 mL of the composition, wherein the total protein content a) comprises or is provided by a source containing a heat-denaturable protein with at least about 55% present in a denatured state, whey protein, and b) a non-whey protein comprising, consisting of, or containing casein, or one or more non-milk proteins, or casein and one or more non-milk proteins, relates to a liquid nutritional composition containing at least about 4 g of whey protein per 100 mL of the composition.

[0015] In a further aspect, the invention is a heat-treated storage-stable liquid nutritional composition having a pH of from about 6.0 to about 8.0, containing at least about 6 g of total protein per 100 mL of the composition, wherein the total protein content a) comprises or is provided by a source containing a heat-denaturable protein with at least about 55% present in a denatured state, whey protein, and b) a non-whey protein comprising, consisting of, or containing casein, or one or more non-milk proteins, or casein and one or more non-milk proteins, wherein the whey protein accounts for at least about 40% by weight of the total protein in the composition, relates to a liquid nutritional composition.

[0016] In another aspect, the invention is a heat-treated storage-stable liquid nutritional composition having a pH of from about 6.0 to about 8.0, containing at least about 6 g of total protein per 100 mL of the composition, wherein the total protein content a) comprises or is provided by a source containing a heat-denaturable protein with at least about 55% present in a denatured state, whey protein, and b) casein, relates to a liquid nutritional composition.

[0017] In another aspect, the present invention is a heat - treated storage - stable liquid nutritional composition having a pH of from about 6.0 to about 8.0, containing at least about 6 g of total protein per 100 mL of the composition, the total protein content being a) containing or provided by a raw material containing a heat - denaturable protein with at least about 55% present in a denatured state, whey protein, and b) casein, and relates to a liquid nutritional composition, wherein the whey protein and casein are present in a weight ratio of at least about 35:65, preferably from about 35:65 to about 80:20.

[0018] In one aspect, the present invention is a method for preparing a liquid nutritional composition, comprising a) providing a liquid composition having a pH of about 6.0 and 8.0, the composition containing at least about 6 g of total protein per 100 mL of the composition, the total protein content being i. containing or provided by a raw material containing a heat - denaturable protein with at least about 55% present in a denatured state, whey protein, and ii. a non - whey protein containing casein, or one or more non - milk proteins, or containing or consisting of casein and one or more non - milk proteins, b) subjecting the liquid composition to a heat treatment with an F0 value of at least 3 to prepare a heat - treated liquid nutritional composition.

[0019] In another aspect, the present invention is a method for preparing a heat - treated storage - stable liquid nutritional composition, comprising a) providing a liquid composition having a pH of from about 6.0 to about 8.0, the composition containing at least about 6 g of total protein per 100 mL of the composition, the total protein content being i. A whey protein comprising or provided by a raw material containing a heat-denaturable protein at least about 55% of which is in a denatured state, the denatured whey protein containing fine particles having a volume-weighted average diameter D[4,3] of less than about 10 μm, ii. A non-whey protein comprising, consisting of, or containing casein, or one or more non-milk proteins, or casein and one or more non-milk proteins, comprising, wherein the whey protein has a degree of hydrolysis of less than about 4%, and the whey protein and the non-whey protein are present in a weight ratio of at least about 35:65, preferably from about 35:65 to about 80:20; b) subjecting the liquid composition to a heat treatment with an F0 value of at least 3 to prepare a heat-treated liquid nutritional composition.

[0020] In one aspect, the present invention provides a heat-treated liquid nutritional composition prepared by the method described herein.

[0021] In one aspect, the present invention provides a method of maintaining or increasing muscle protein synthesis, maintaining or increasing muscle mass, preventing or reducing loss of muscle mass, maintaining or increasing growth, preventing or reducing muscle catabolism, preventing or treating cachexia, preventing or treating sarcopenia, increasing glycogen resynthesis rate, regulating blood glucose level, increasing insulin response to elevated blood glucose concentration, reducing satiety, reducing boredom, reducing food intake, reducing calorie intake, improving glucose metabolism, increasing postoperative recovery rate, increasing preoperative rehabilitation effect before surgery or chemotherapy, increasing recovery rate after injury, increasing recovery rate after exercise, increasing sports performance, and / or providing nutrients to a subject in need thereof, the method comprising administering the liquid nutritional composition described herein to the subject.

[0022] In another aspect, the present invention provides for the use of the liquid nutritional composition described herein in the preparation of a composition, preferably a nutritional agent or a medicament, for maintaining or increasing muscle protein synthesis, maintaining or increasing muscle mass, preventing or reducing loss of muscle mass, maintaining or increasing growth, preventing or reducing muscle catabolism, preventing or treating cachexia, preventing or treating sarcopenia, increasing the rate of glycogen resynthesis, regulating blood glucose levels, increasing the insulin response to an increase in blood glucose concentration, reducing satiety, reducing boredom, reducing food intake, reducing calorie intake, improving glucose metabolism, increasing the rate of recovery after surgery, increasing the prehabilitation effect before surgery or chemotherapy, increasing the rate of recovery after injury, increasing the rate of recovery after exercise, increasing sports performance, and / or providing nutrients to a subject in need thereof.

[0023] In a further aspect, the present invention provides the liquid nutritional composition described herein for maintaining or increasing muscle protein synthesis, maintaining or increasing muscle mass, preventing or reducing loss of muscle mass, maintaining or increasing growth, preventing or reducing muscle catabolism, preventing or treating cachexia, preventing or treating sarcopenia, increasing the rate of glycogen resynthesis, regulating blood glucose levels, increasing the insulin response to an increase in blood glucose concentration, reducing satiety, reducing boredom, reducing food intake, reducing calorie intake, improving glucose metabolism, increasing the rate of recovery after surgery, increasing the prehabilitation effect before surgery or chemotherapy, increasing the rate of recovery after injury, increasing the rate of recovery after exercise, increasing sports performance, and / or providing nutrients to a subject in need thereof.

[0024] Any of the embodiments or preferred forms described herein may be related to any of the aspects herein, alone or in combination with any one or more of the embodiments or preferred forms described herein, unless otherwise stated or shown.

[0025] In various embodiments, the liquid nutritional composition has a pH of about 6, 6.1, 6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8, 6.9, 7.0, 7.1, 7.2, 7.3, 7.4, 7.5, 7.6, 7.7, 7.8, 7.9, or about 8.0, and various ranges can be selected from between these values, for example, about 6.0 to about 8.0, about 6.0 to about 7.5, about 6.0 to about 7.2, about 6.0 to about 7.0, about 6.2 to about 8.0, about 6.2 to about 7.5, about 6.2 to about 7.2, about 6.2 to about 7.0, about 6.4 to about 8.0, about 6.4 to about 7.5, about 6.4 to about 7.2, about 6.4 to about 7.0, or about 6.5 to about 8.0, about 6.5 to about 7.5, about 6.5 to about 7.2, or about 6.5 to about 7.0.

[0026] In various embodiments, the liquid nutritional composition contains a total protein content of at least about 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 27, or at least about 30 g per 100 mL of the composition, and various ranges can be selected from between these values, for example, about 6 to about 30 g, about 7 to about 30, about 8 to about 30, about 9 to about 30, about 10 to about 30, 6 to about 25 g, about 7 to about 25, about 8 to about 25, about 9 to about 25, about 10 to about 25, about 11 to 25, about 12 to 25, about 13 to about 25, about 14 to about 25, about 15 to about 25, about 6 to about 20 g, about 7 to about 20, about 8 to about 20, about 9 to about 20, about 10 to about 20, or about 10 to about 15 g of total protein per 100 mL of the composition. In various embodiments, the liquid nutritional composition contains a total protein content of at least about 9 g of protein per 100 mL of the composition, or at least about 10 g of protein per 100 mL of the composition, or at least about 12 g of protein per 100 mL of the composition.

[0027] In various embodiments, whey protein and non-whey protein, whey protein and casein, or whey protein and one or more non-milk proteins are present in the composition in a weight ratio of at least about 20:80, 25:75, 30:70, 35:65, 40:60, 45:55, 50:50, 55:45, 60:40, 65:35, 70:30, 75:25, 80:20, 85:15, 90:10, 95:5, or at least about 99:1, and various ranges can be selected from between these values, for example, about 30:70 to about 80:20, about 35:65 to about 80:20, about 40:60 to about 80:20, about 45:55 to about 80:20, about 50:50 to about 80:20, about 30:70 to about 75:25, about 35:65 to about 75:25, about 40:60 to about 75:25, about 45:55 to about 75:25, about 50:50 to about 75:25, about 30:70 to about 70:30, about 35:65 to about 70:30, about 40:60 to about 70:30, about 45:55 to about 70:30, or about 50:50 to about 70:30, about 30:70 to about 65:35, about 35:65 to about 65:35, about 40:60 to about 65:35, about 45:55 to about 65:35, about 50:50 to about 65:35, about 30:70 to about 60:40, about 35:65 to about 60:40, about 40:60 to about 60:40, about 45:55 to about 60:40, or about 50:50 to about 60:40. In one preferred embodiment, the ratio can be at least about 35:65, more preferably about 35:65 to about 80:20.

[0028] In various embodiments, the composition contains at least about 0.01, 0.1, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or at least about 20 g of non-whey protein per 100 mL of the composition, and various ranges can be selected from between any of these values, for example, about 0.01 to about 2, 1 to about 20, 2 to about 20, 3 to about 20, 4 to about 20, 5 to about 20, 0.01 to about 15, 1 to about 15, 2 to about 15, 3 to about 15, 4 to about 15, 5 to about 15, 0.01 to about 10, 1 to about 10, 2 to about 10, 3 to about 10, 4 to about 10, or about 5 to about 10 g of non-whey protein per 100 mL of the composition.

[0029] In various embodiments, the non-whey protein comprises at least about 1, 2, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, or at least about 95 weight percent of the total protein in the composition, and various ranges can be selected between any of these values, for example, from about 1 weight percent to about 99 weight percent, 10 weight percent to about 95 weight percent, about 10 weight to about 80 weight percent, about 10 weight percent to about 70 weight percent, about 10 weight percent to about 65 weight percent, about 10 weight percent to about 60 weight percent, about 15 weight percent to about 95 weight percent, about 15 weight percent to about 80 weight percent, about 15 weight percent to about 70 weight percent, about 15 weight percent to about 65 weight percent, about 15 weight percent to about 60 weight percent, about 20 weight percent to about 80 weight percent, about 20 weight percent to about 70 weight percent, about 20 weight percent to about 65 weight percent, or about 20 weight percent to about 60 weight percent of the total protein in the composition.

[0030] In one embodiment, the non-whey protein is at least partially hydrolyzed. In another embodiment, the non-whey protein is not hydrolyzed. In various embodiments, the non-whey protein has a degree of hydrolysis of about 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, 95, or less than at least about 99%, and various ranges can be selected between any of these values, for example, from about 0 to about 99, 1 to about 99%, about 5 to about 99%, about 10 to about 99%, about 20 to about 99%, about 50 to about 99%, about 0 to about 95, about 1 to about 95%, about 5 to about 95%, about 10 to about 95%, about 20 to about 95%, about 50 to about 95%, about 0 to about 90, about 1 to about 90%, about 5 to about 90%, about 10 to about 90%, about 20 to about 90%, about 50 to about 90%, about 0% to about 50%, about 1% to about 50%, about 0% to about 25%, about 1% to about 25%, about 0% to about 20%, about 1% to about 20%, about 0% to about 10%, about 1% to about 10%, about 0% to about 5%, or about 1% to about 5%.

[0031] In various embodiments, the whey protein comprises, consists essentially of, or consists of a starting material that comprises, consists essentially of, or consists of a heat-denaturable protein in which at least about 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or at least about 95% is in a denatured state, or is provided thereby.

[0032] In various embodiments, the denatured whey protein can include microparticles having a volume-weighted mean diameter D[4,3] of less than about 10, 9.5, 9, 8.5, 8, 7.5, 7, 6.5, 6, 5.5, 5, 4.5, 4, 3.5, 3, 2.5, or 2 μm. In various preferred embodiments, the volume-weighted mean diameter D[4,3] can be less than about 5 μm, or less than about 3 μm, or less than about 2 μm. Preferably, the volume-weighted mean diameter D[4,3] is less than about 10 μm, or less than about 5 μm, or less than about 3 μm, or less than about 2 μm.

[0033] In various embodiments, the whey protein may not be hydrolyzed. In various embodiments, the whey protein can have a degree of hydrolysis of less than about 5%, 4.75%, 4.5%, 4.25%, 4%, 3.75%, 3.5%, 3.25%, 3%, 2.75%, 2.5%, 2.25%, 2%, 1.75%, 1.5%, 1.25%, 1%, 0.75%, or about 0.5%. In various preferred embodiments, the whey protein can have a degree of hydrolysis of less than about 4%.

[0034] In certain embodiments, the whey protein is provided by a blend of whey protein sources including whey protein concentrate (WPC), whey protein isolate (WPI), or a blend of WPC and / or WPI. In some embodiments, the whey protein is provided by a raw material including WPC, WPI, or a blend thereof, and a whey protein and a non-whey protein (e.g., casein). In one embodiment, the raw material including a whey protein and a non-whey protein is selected from the group consisting of milk protein concentrate (MPC); total milk protein (TMP); milk co-precipitate; micellar casein concentrate (MCC); milk protein isolate (MPI); protein of sweetened condensed milk; skim milk; skim milk powder; sweetened skim milk; whole milk; whole milk powder; or any combination of two or more thereof.

[0035] In one embodiment, the whey protein is provided by a raw material having a protein content of 35 wt% to 95 wt% of the dry matter raw material.

[0036] In certain embodiments, the whey protein raw material contains at least about 35 wt%, 50 wt%, 65 wt%, 70 wt%, 75 wt%, or at least about 80 wt% protein. In certain embodiments, a composition with a higher protein content is utilized. For example, the whey protein raw material contains at least about 85 wt%, 90 wt%, or at least about 95 wt% protein.

[0037] In various embodiments, the composition includes a whey protein raw material that has been treated to reduce its lactose concentration, e.g., WPC or WPI. In various embodiments, the whey protein raw material contains less than about 10, 9, 8, 7, 6, 5, 4, 3, 2, 1, 0.5%, or less than about 0.1% lactose.

[0038] In various embodiments, the composition contains at least about 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or at least about 20 g of whey protein per 100 mL of the composition, and various ranges can be selected from among any of these values. For example, the composition contains about 2 to about 20, 4 to about 20, about 5 to about 20, about 6 to about 20, about 7 to about 20, about 2 to about 15, about 4 to about 15, about 5 to about 15, about 6 to about 15, or about 7 to about 15 g of whey protein per 100 mL of the composition.

[0039] In various embodiments, the whey protein accounts for at least about 1, 2, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, or at least about 95 wt% of the total protein in the composition, and various ranges can be selected from among any of these values. For example, the whey protein accounts for about 1 wt% to about 99 wt%, 10 wt% to about 95 wt%, about 20 wt% to about 80 wt%, about 35 wt% to about 80 wt%, about 40 wt% to about 95 wt%, or about 40 wt% to about 80 wt% of the total protein in the composition.

[0040] In one embodiment, the casein contains or is provided by a raw material containing soluble casein. In various embodiments, the casein is micellar casein, non-micellar casein, or micellar and non-micellar casein.

[0041] In various embodiments, the casein comprises, or is provided by, a raw material comprising casein, such as milk protein isolate (MPI); milk protein concentrate (MPC); micellar casein isolate (MCI); micellar casein concentrate (MCC); protein of sweetened condensed milk; skim milk; skim milk powder; sweetened skim milk; whole milk; whole milk powder; casein salt; total milk protein (TMP); milk co-precipitate; MPC or MPI modified to dissociate casein micelles; calcium chelated casein micelles; charge modified casein; a casein raw material such as MPC or MPI in which at least a part of calcium or phosphate or both calcium and phosphate are replaced with sodium, potassium, zinc, magnesium, or a combination of two or more thereof; glycosylated casein; or a combination of two or more thereof.

[0042] In various embodiments, the casein comprises, or is provided by, a casein raw material such as MPC or MPI in which at least a part of calcium or phosphate or both calcium and phosphate are replaced with sodium, potassium, zinc, magnesium, or a combination of two or more thereof.

[0043] In various embodiments, the casein salt comprises sodium caseinate, calcium caseinate, magnesium caseinate, potassium caseinate, or a combination of two or more thereof.

[0044] In various embodiments, the composition comprises a casein raw material, such as MPC or MPI, that has been treated to reduce the lactose concentration. In various embodiments, the casein raw material comprises less than about 10, 9, 8, 7, 6, 5, 4, 3, 2, 1, 0.5%, or less than about 0.1% lactose.

[0045] In various embodiments, casein comprises at least about 1 wt%, 5 wt%, 10 wt%, 15 wt%, 20 wt%, 25 wt%, 30 wt%, 35 wt%, 40 wt%, 45 wt%, 50 wt%, 55 wt%, 60 wt%, 65 wt%, 70 wt%, or at least about 75 wt% of the total protein in the composition, and various ranges can be selected from between these values, for example, from about 1 wt% to about 75 wt%, from about 5 wt% to about 75 wt%, from about 1 wt% to about 65 wt%, 5 wt% to about 65 wt%, from about 10 wt% to about 65 wt%, from about 20 wt% to about 65 wt%, from about 30 wt% to about 65 wt%, or from about 40 wt% to about 65 wt%.

[0046] In various embodiments, the composition comprises at least about 0, 0.01, 0.1, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or at least about 20 g of casein per 100 mL of the composition, and various ranges can be selected from between any of these values, for example, from about 0 to about 20, from about 0.01 to about 20, 4 to about 20, from about 5 to about 20, from about 6 to about 20, from about 7 to about 20, from about 0 to about 15, from about 0.01 to about 15, from about 4 to about 15, from about 5 to about 15, from about 6 to about 15, or from about 7 to about 15 g of casein per 100 mL of the composition.

[0047] In one embodiment, the casein is not hydrolyzed. In another embodiment, the casein is at least partially hydrolyzed.

[0048] In one embodiment, the composition comprises one or more non-milk proteins. In various embodiments, the non-milk proteins include algal proteins, hydrolyzed algal proteins, plant proteins, hydrolyzed plant proteins, animal proteins, or hydrolyzed animal proteins, or any combination of two or more thereof.

[0049] In various embodiments, the plant protein includes canola, legume, cereal, nut, or seed protein, or any combination of two or more thereof, and optionally, any one or more of the plant proteins is a hydrolyzed plant protein. In various embodiments, the legume protein includes pea, chickpea, bean, mung bean, lentil, or soybean protein, or any combination of two or more thereof, and optionally, any one or more of the plant proteins is a hydrolyzed plant protein. In various embodiments, the cereal protein includes rice, wheat, sorghum, corn, maize, or barley protein, or any combination of two or more thereof, and optionally, any one or more of the plant proteins is a hydrolyzed plant protein. In various embodiments, the nut protein includes almond or cashew protein, or any combination thereof, and optionally, any one or more of the plant proteins is a hydrolyzed plant protein. In various embodiments, the seed protein includes chia, flax, or hemp protein, or any combination of two or more thereof, and optionally, any one or more of the plant proteins is a hydrolyzed plant protein.

[0050] In various embodiments, the animal protein can include collagen, hydrolyzed collagen, recombinant collagen, hydrolyzed recombinant collagen, or any combination of two or more thereof.

[0051] In various embodiments, the non-dairy protein has a pI of about 3, 3.1, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, 4, 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9, 5, 5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, or about 6, and various ranges can be selected between these values, for example, about 3 to about 6, about 3.5 to about 6, about 4 to about 6, about 3 to about 5.5, about 3.5 to about 5.5, about 4 to about 5.5, about 3 to about 5, about 3.5 to about 5, or about 4 to about 5.

[0052] In various embodiments, the composition contains at least about 0, 0.01, 0.1, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, or at least about 30 g of non-dairy protein per 100 mL of the composition, and various ranges can be selected between these values, for example, per 100 mL of the composition, about 0 to about 30, about 0.01 to about 30, about 1 to about 30, about 0 to about 20, about 0.01 to about 20, about 0.1 to about 20, about 0.5 to about 20, about 0.1 to about 15, about 1 to about 20, about 2 to about 20, about 3 to about 20, about 5 to about 20, about 0 to about 10, about 0.01 to about 10, about 1 to about 10 g of non-dairy protein.

[0053] In various embodiments, the composition contains at least about 0.01, 0.1, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, or at least about 30 g of lipid per 100 mL of the composition, and various ranges can be selected between these values, for example, per 100 mL of the composition, about 0.01 to about 30, about 0.1 to about 30, about 1 to about 30, about 0.01 to about 25, about 0.1 to about 25, about 1 to about 25, about 0.01 to about 20, about 0.1 to about 20, about 0.5 to about 20, about 1 to about 20, about 2 to about 20, about 3 to about 20, about 5 to about 20 g, about 0.01 to about 15, about 0.1 to about 15, about 1 to about 15, about 2 to about 15, about 5 to about 15, about 0.01 to about 10, about 0.1 to about 10, about 1 to about 10, or about 2 to about 10 g of lipid.

[0054] In various embodiments, the composition contains at least about 0.01, 0.1, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, or at least about 45 g of carbohydrates per 100 mL of the composition, and various ranges can be selected from between these values. For example, per 100 mL of the composition, it is about 0.01 to about 4, about 0.01 to about 45, about 0.1 to about 45, about 1 to about 45, about 4 to about 45, about 5 to about 45, about 0.01 to about 40, about 0.1 to about 40, about 1 to about 40, about 4 to about 40, about 5 to about 40, about 0.01 to about 30, about 1 to about 30, about 1 to about 30, about 4 to about 30, about 5 to about 30, 0.01 to about 20, about 0.1 to about 20, about 0.5 to about 20, about 0.1 to about 15, about 1 to about 20, about 2 to about 20, about 3 to about 20, about 4 to about 20, or about 5 to about 20 g of carbohydrates.

[0055] In various embodiments, the carbohydrates include digestible carbohydrates, indigestible carbohydrates, or combinations thereof.

[0056] In various embodiments, the composition has an energy density of at least about 25, 50, 75, 100, 125, 150, 200, 250, 300, 350, or at least about 400 kcal per 100 mL, and various ranges can be selected from between these values. For example, per 100 mL of the composition, it is about 25 to about 400, 50 to about 400, about 100 to about 400, about 150 to about 400, about 175 to about 400, about 50 to about 350, about 50 to about 300, about 100 to about 300, about 25 to about 300, about 50 to about 300, about 100 to about 300, about 25 to about 250, about 50 to about 250, about 100 to about 250, about 25 to about 200, about 50 to about 200, or about 100 to about 200 kcal. In various preferred embodiments, the composition has an energy density of at least about 200 kcal per 100 mL of the composition.

[0057] In various embodiments, the composition comprises, consists essentially of, or consists of disaccharides, oligosaccharides, and / or polysaccharides containing one glucose unit or no glucose units, less than 0 g, or about 0.5, 1, 2, 3, 4, or 5 g per 100 mL of the composition. Various ranges can be selected between these values, for example, from about 0 to about 5, from about 0 to about 4, or from about 0.01 to about 4 g per 100 mL of the composition.

[0058] In various embodiments, the composition comprises at least about 0, 0.01, 0.025, 0.05, 0.075, 0.1, 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45, or 0.5 g of an emulsifier and / or surfactant per 100 mL of the composition. Various ranges can be selected between these values, for example, from about 0 to about 0.5, from about 0.01 to about 3, or from about 0.01 to about 0.2 g per 100 mL of the composition.

[0059] In various embodiments, the composition comprises at least about 0.001, 0.002, 0.003, 0.004, 0.005, 0.006, 0.007, 0.008, 0.009, 0.01, 0.015, 0.02, 0.025, 0.03, 0.035, 0.04, 0.045, 0.05, 0.055, 0.06, 0.065, 0.07, 0.075, 0.08, 0.085, 0.09, 0.095, or 0.1 g of an emulsifier per gram of lipid. Various ranges can be selected between these values, for example, from about 0.001 to about 0.1, from about 0.002 to about 0.08, or from about 0.003 to about 0.06 g per gram of lipid.

[0060] In various embodiments, the composition has a viscosity of less than about 500, 450, 400, 300, 200, 150, 100, 80, 60, 50, 40, 30 mPa·s, or less than about 20 mPa·s when measured at a temperature of 20 °C and a shear rate of 100 s -1 .

[0061] In one embodiment, the composition does not substantially exhibit gelation or aggregation.

[0062] In various embodiments, when classified by the surface weight average particle size parameter d[3,2] and / or the volume weight average diameter D[4,3], the composition has an average particle size of less than about 20, 18, 15, 12, 10, 9, 8, 7, 6, 5, 4, 3, 2.5, 2, 1.5, 1, 0.9, 0.8, 0.7, 0.6, 0.5, 0.4, 0.3, or 0.25 μm, and the useful range can be selected between any of these values, for example, from about 0.25 to about 20, from about 0.25 to about 15, from about 0.25 to about 10, from about 0.25 to about 8, from about 0.25 to about 6, or from about 0.25 to about 4 μm.

[0063] In various embodiments, the composition can contain, consist essentially of, or consist of a total amount of monovalent metal ions of at least about 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, or 50 mg per gram of protein, and the useful range can be selected between these values, for example, from about 8 to about 20, from about 8 to about 30, from about 8 to about 40, from about 8 to about 50, from about 10 to about 50, from about 15 to about 50, from about 20 to about 50, and from about 50 to about 50 mg per gram of protein. In various embodiments, the monovalent metal ions can include sodium ions, potassium ions, or both.

[0064] In various embodiments, the composition can contain, consist essentially of, or consist of an amount of monovalent metal ions of at least about 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 225, 250, 275, 300, 325, 350, 375, 400, 425, 450, 475, or 500 mg per 100 mL of the composition, and the useful range can be selected between any of these values, for example, from about 50 to about 500, from about 100 to about 400, from about 150 to about 350, or from about 100 to about 500 mg per 100 mL.

[0065] In various embodiments, the composition can contain, consist essentially of, or consist of calcium in an amount of at least about 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 225, 250, 275, 300, 325, 350, 375, 400, 425, 450, 475, or 500 mg per 100 mL of the composition, and a useful range can be selected between any of these values, for example, about 50 to about 500, about 100 to about 400, about 150 to about 350, or about 100 to about 500 mg of calcium per 100 mL.

[0066] In various embodiments, the protein in the composition remains soluble in the upper gastrointestinal tract, remains soluble in the upper gastrointestinal fluid, does not form a precipitate in the upper gastrointestinal tract, or does not form a precipitate in the upper gastrointestinal fluid.

[0067] In various embodiments, the protein in the composition remains soluble or does not form a precipitate at a pH of about 1, 2, 3, 4, or about 5. In one embodiment, the protein in the composition remains soluble or does not form a precipitate when simulated gastric fluid, for example, simulated gastric fluid prepared as described herein in the examples (containing hydrochloric acid, protease, and lipase, preferably containing hydrochloric acid, pepsin, and lipase A, more preferably containing 1 M hydrochloric acid, 16 mg / mL pepsin, and 2 mg / mL lipase A) is added to the composition. In various embodiments, the volume-weighted average diameter D[4,3] and / or surface-weighted average diameter D[3,2] of the protein microparticles in the composition is preferably less than about 10 μm, or less than about 5 μm, or less than about 3 μm, or less than about 2 μm over a period of 220 minutes at a pH of less than about 4, preferably in the presence of simulated gastric fluid.

[0068] In various embodiments, the composition is stored at a temperature of 20, 22, or 25 °C for at least 2 months, 3 months, 6 months, or at least 12 months, and then at a temperature of 20 °C and a shear rate of 100 s -1 and has a viscosity of less than about 500, 450, 400, 300, 200, 150, 100, 80, 60, 50, 40, 30 mPa·s, or less than about 20 mPa·s when measured.

[0069] In various embodiments, the viscosity of the composition is stored at a temperature of 20, 22, or 25 °C for at least 2 months, 3 months, 6 months, or 12 months, and then at a temperature of 20 °C and a shear rate of 100 s -1 and increases by less than about 10, 20, 30, 40, 50, 60, 70, 80, 90%, or less than about 100% when measured.

[0070] In various embodiments, the composition does not exhibit observable gelation, observable aggregation, observable sedimentation, or any combination of two or more thereof, when stored at a temperature of 20, 22, or 25 °C for at least 2 months, 3 months, 6 months, or at least 12 months.

[0071] In various embodiments, the composition can be subjected to a heat treatment with an F0 value of at least 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, or 40 (and increases in half-units thereof, e.g., 19.5), and a useful range can be selected between these values, e.g., 3 - 20, 3 - 30, 3 - 40, 10 - 20, 10 - 30, or 10 - 40.

[0072] In various embodiments, when subjected to a heat treatment with an F0 value of at least 3, e.g., 121.1 °C for 3 minutes, 130 °C for 25 seconds, 135 °C for 7.5 seconds, 140 °C for 2.5 seconds, 145 °C for 0.75 seconds, or 150 °C for 0.25 seconds, the composition a) does not substantially exhibit gelation, aggregation, or sedimentation, or b) When measured at a temperature of 20 °C and a shear rate of 100 s -1 it has a viscosity of less than about 500 mPa·s, or c) When classified by volume weighted average diameter D[4,3] and / or surface weighted average particle size parameter d[3,2], it has an average particle size of less than about 20, 18, 15, 12, 10, 9, 8, 7, 6, 5, 4, 3, 2.5, 2, 1.5, 1, 0.9, 0.8, 0.7, 0.6, 0.5, 0.4, 0.3, or 0.25 μm, or d) Exhibits any combination of two or more of the above a) - c).

[0073] In one embodiment, the heat - treated liquid nutritional composition a) When measured at 20 °C and a shear rate of 100 s -1 it has a viscosity of less than about 500 mPa·s, or b) When classified by volume weighted average diameter D[4,3] and / or surface weighted average particle size parameter d[3,2], it has an average particle size of less than about 20 μm, or c) Does not substantially exhibit observable gelation or aggregation or sedimentation, or d) Exhibits any combination of two or more of the above (a) - (c).

[0074] In one embodiment, the heat treatment has an F0 value of at least 3. In various embodiments, the heat treatment has an F0 value corresponding to at least 121.1 °C for 3 minutes, 130 °C for 25 seconds, 140 °C for 2.5 seconds, or 150 °C for 0.25 seconds. In one embodiment, the heat treatment is sufficient to provide a product with storage stability.

[0075] In various embodiments, the method includes heat-treating a liquid composition at a temperature of at least about 121, 125, 130, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, or at least about 150 °C for a period of at least about 0.1, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 15, 20, 30, 40, 50, 60 seconds, or at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, or at least about 10 minutes. Various ranges can be selected from between any of these values. For example, in various embodiments, the method includes heat-treating a liquid composition at a temperature of at least about 121 to about 150, 125 to about 150, 130 to about 150, 135 to about 150, 138 to about 150, 121 to about 145, 125 to about 145, 130 to about 145, 135 to about 145, or about 138 to about 145 °C for a period of at least about 0.1 seconds to about 10 minutes, about 0.1 seconds to about 1 minute, about 0.1 seconds to about 30 seconds, about 0.5 seconds to about 30 seconds, about 1 second to about 30 seconds, about 3 seconds to about 30 seconds, about 0.1 seconds to about 20 seconds, about 0.5 to about 20 seconds, about 1 to about 20 seconds, about 3 to about 20 seconds, about 0.1 to about 10 seconds, about 1 to about 10 seconds, about 3 to about 10 seconds, about 0.1 to about 7 seconds, about 1 to about 7 seconds, about 3 to about 7 seconds, about 0.1 to about 5 seconds, about 1 to about 5 seconds, or about 3 seconds to about 5 seconds.

[0076] In one embodiment, the heat treatment is an indirect heat treatment. In another embodiment, the heat treatment is a direct heat treatment.

[0077] In one embodiment, the liquid composition has a pH greater than 6.0, 6.5, 7.0, or 7.5 when heat-treated.

[0078] In one embodiment, the method further includes drying the heat-treated liquid composition.

[0079] In one exemplary embodiment, the heat-treated liquid composition is not subjected to further heat treatment before packaging or consumption. In one exemplary embodiment, the heat-treated liquid composition is not subjected to further sterilization before packaging or consumption. In one exemplary embodiment, no additional ingredients are added to the heat-treated liquid composition before packaging or consumption so that its composition does not change.

[0080] In one embodiment, the method further includes aseptic processing, bottling, and / or packaging the heat-treated liquid composition.

[0081] In various embodiments, the person in need of nutrition may be suffering from or be prone to a disease or illness, or may have undergone or be undergoing treatment for a disease or illness, and may be an elderly person, a person recovering from a disease or illness, or a malnourished person. In other embodiments, this person may also be a healthy person, such as an athlete or an active elderly person, including those with specific nutritional requirements.

[0082] The present invention also broadly speaking can be said to consist of the parts, elements and features individually or collectively mentioned or shown in the specification of this patent application, and any or all combinations of any two or more of said parts, elements or features, and where specific integers having known equivalents in the technical field to which the present invention relates are described herein, such known equivalents are considered to be incorporated herein as if individually described.

[0083] References to numerical ranges (e.g., 1 to 10) disclosed herein are also intended to include references to all rational numbers within that range (e.g., 1, 1.1, 2, 3, 3.9, 4, 5, 6, 6.5, 7, 8, 9, and 10) and references to any range of rational numbers within that range (e.g., 2 to 8, 1.5 to 5.5, and 3.1 to 4.7). Accordingly, all sub-ranges of all ranges explicitly disclosed herein are also explicitly disclosed herein. These are merely examples of what is specifically intended, and all possible combinations of numerical values between the recited minimum and maximum values are likewise considered to be explicitly stated herein.

[0084] When referring in this specification to external information sources including patent specifications and other documents, this is generally for the purpose of providing background to describe the features of the invention. Unless otherwise specified, reference to such information sources should not be construed in any jurisdiction as an admission that such information sources are prior art or form part of the common general knowledge in the art.

Brief Description of the Drawings

[0085] Here, the present invention will be described with reference to the following drawings by way of mere example.

Figure 1

Figure 2

Figure 3

Embodiments for Carrying Out the Invention

[0086] The present invention provides a heat - treated, storage - stable, neutral pH, high - protein liquid nutritional composition comprising both whey protein and non - whey protein. Surprisingly, the inventors have found that by combining whey protein with a second protein source comprising casein and / or one or more non - milk proteins, a neutral pH, high - protein (especially high - whey - protein) liquid nutritional composition that is stable to the high - temperature heat treatment necessary to achieve storage stability and microbial control is produced. In various embodiments, the liquid nutritional composition remains soluble at low pH such that post - consumption digestive coagulation is controlled and coagulum formation in the upper gastrointestinal tract is reduced or eliminated. Advantageously, in various embodiments, the high - protein liquid nutritional composition described herein has a lower viscosity compared to an equivalent high - protein liquid composition containing hydrolyzed casein as the main or sole protein source. A low viscosity of the liquid nutritional composition is desirable to facilitate administration and consumption.

[0087] 1. Definitions The phrase “calcium - reduced” as used herein refers to a casein composition, such as a milk protein concentrate (MPC), in which the concentration of calcium bound to casein is decreased and is lower than the concentration of calcium bound to casein in the corresponding non - reduced composition. Such a composition may also have a lower concentration of divalent cations, such as magnesium, bound to casein than the corresponding non - reduced composition, since other divalent cations may also be reduced. Similarly, reference to calcium in a casein protein is a reference to bound calcium, i.e., calcium bound by the casein protein.

[0088] As used herein, the term "comprising" means "consisting at least in part of". When interpreting a reference in this specification that includes that term, or a feature starting with that term in each reference, all of the components recited must be present, but other components can also be present. Related terms such as "comprise" and "comprised" should be interpreted in the same manner.

[0089] "Effective amount" means the amount necessary to provide a therapeutic effect. The interrelationship of dosages for animals and humans (based on milligrams per square meter of body surface) has been described by Freireich et al., 1966 (see Freireich EJ, Gehan EA, Rall DP, Schmidt LH, Skipper HE (1966) Quantitative comparison of toxicity to anticancer agents in mouse, rat, hamster, dog, monkey and man. Cancer Chemother Rep 50:219 - 244). Body surface area can be approximately determined from the height and weight of the subject. See, for example, Scientific Tables, Geigy Pharmaceuticals, Ardley, New York, 1970, 537. As recognized by those skilled in the art, the effective dosage can vary depending on the route of administration, the use of carriers, etc.

[0090] The term "liquid nutritional composition" refers to an aqueous composition that should preferably be administered to the patient's stomach orally or by other means, generally by enteral nutrition. Such other means include nasogastric nutrition and gastrostomy nutrition. Examples of liquid nutritional compositions include "medical foods", "enteral nutrition", "foods for special medical purposes", liquid meal replacements, and nutritional supplements. The liquid nutritional compositions of the present invention provide a significant amount of protein and carbohydrates, and usually also lipids. They may also contain vitamins and minerals. In an exemplary embodiment, they provide a balanced diet.

[0091] The term "milk protein concentrate" (or MPC) refers to a milk protein product in which more than 55%, preferably more than 75% of the dry matter is milk protein, and the ratio of casein to whey protein is approximately that of milk. Such concentrates are known in the art.

[0092] The phrase "maintaining or increasing muscle mass", and its grammatical equivalents and derivatives, refers to increasing muscle protein synthesis and / or reducing muscle protein breakdown to increase or maintain muscle mass.

[0093] As used herein, "non-milk protein" includes any protein that is not a milk protein, i.e., any protein not derived from mammalian milk. Non-milk proteins include plant-derived proteins and algal proteins.

[0094] As used herein, in the context of a protein-containing composition, "non-whey protein" includes any protein that is not a whey protein. Non-whey proteins useful in the compositions described herein include casein, and proteins derived from one or more non-milk sources.

[0095] The phrase "preventing or reducing loss of muscle mass", and its grammatical equivalents and derivatives, refers to preventing or reducing muscle protein breakdown to result in maintenance of muscle mass or a decrease in the rate of muscle loss.

[0096] As used herein in connection with a liquid nutritional composition, the term "storage stability" means that the composition remains in a liquid state with substantially no sedimentation, gelling, or aggregation observed, and with negligible bacterial growth upon aseptic packaging after long-term storage at a temperature of about 20 °C, 22 °C, or about 25 °C for at least about 2 months, 3 months, about 6 months, or at least about 12 months.

[0097] "Subject" refers to vertebrates that are mammals, such as humans. Mammals include, but are not limited to, humans, livestock, sports animals, pets, primates, mice, and rats.

[0098] Unless otherwise specified, the whey proteins and non-whey proteins used in this specification are substantially non-hydrolyzed.

[0099] As used herein, the term "substantially non-hydrolyzed" includes non-hydrolyzed (as-is) proteins and proteins having a degree of hydrolysis of less than about 4%, 3.75%, 3.5%, 3.25%, 3%, 2.75%, 2.5%, 2.25%, 2%, 1.75%, 1.5%, 1.25%, 1%, 0.75%, or less than about 0.5%.

[0100] As used herein, the term "whey protein concentrate (WPC)" refers to a whey fraction in which lactose has been at least partially removed to increase the protein content to at least 20% by weight. In certain embodiments, the WPC has at least 35% by weight, at least 40% by weight, at least 55% by weight, at least 65% by weight, and in certain embodiments at least 80% by weight of the total solids (TS) as whey protein. In some examples, the ratio of whey protein is substantially unchanged relative to the ratio of the whey from which the WPC is derived. In one embodiment, the WPC is a whey protein holding solution with water removed. For the purposes of this specification, the term "WPC" includes whey protein isolate (WPI) if appropriate in the context.

[0101] As used herein, the term "whey protein isolate" refers to a composition consisting primarily of whey protein having a negligible lipid and lactose content. Thus, the preparation of WPI typically requires a more rigorous separation process, such as a combination of microfiltration and ultrafiltration or ion exchange chromatography. Generally, WPI is recognized to refer to a composition in which at least 90% by weight of the solids is whey protein.

[0102] Particularly contemplated whey protein sources include WPI and WPC having at least 90% TS as the whey protein.

[0103] 2. Liquid nutritional composition The liquid nutritional composition may also include a variety of vitamins and minerals required to nutritionally support a patient over a long period of time, as well as minor components such as antioxidants, flavorings, and colorants. The amounts of vitamins and minerals used in certain embodiments are typical of meal replacement products known to those skilled in the art. The micronutrient requirements of various subgroups of the population are also known. The recommended daily requirements of vitamins and minerals can be specified for various population subgroups. See, for example, the Dietary Reference Intakes: RDA and AI for vitamins and elements, United States National Academy of Sciences, Institute of Medicine, Food and Nutrition Board (2010) tables for recommended intakes for infants from 0 to 6 months, 6 to 12 months, children from 1 to 3 years and 4 to 8 years, adult males (6 age classes), females (6 age classes), pregnant women (3 age classes), and lactating women (3 age classes). The concentration of essential nutrients in the liquid nutritional composition can be adjusted to match the exemplary specified dosages for a particular subgroup or medical condition or use so as to simultaneously meet the requirements of the nutrients and ease of delivery.

[0104] For example, the levels of minerals added can be selected based on the European Commission guidelines for foods for special medical purposes (FSMP) directives. For specific nutritional reasons, it is possible to choose to add higher levels. Examples of the compositions of the present invention having very good thermal stability at a pH of about 6-8 in the presence of various amounts of minerals.

[0105] In one embodiment, the composition contains at least about 10, 20, 25, 30, 40, 50, 60, 70, 75, 80, 90, or 100% of the recommended daily intake (RDI) of vitamins and minerals set by European (FSMP) or USDRA regulations in a 100 mL, 250 mL, 500 mL, or 1 L portion.

[0106] The lipids used can be vegetable lipids or animal lipids including milk fat and fish oil. Vegetable oils are often cited as examples because they are easy to formulate and have a low saturated fatty acid content. Exemplary vegetable oils include canola oil, corn oil, sunflower oil, olive oil, or soybean oil.

[0107] In various embodiments, the composition contains a stabilizer or an emulsifier. Emulsifiers useful for stabilizing fat droplets include lecithin, monoglycerides and diglycerides, polyglycerol esters, milk phospholipids, citrate esters (citrem), and dativem. These emulsifiers can be added in an amount of about 0.003 g to about 0.06 g per gram of lipid. Useful stabilizers include carrageenan, gellan gum, pectin, guar gum, locust bean gum, carboxymethyl cellulose, and microcrystalline cellulose, and combinations thereof. Those skilled in the art will recognize that in addition to those listed above, many different gum forms are suitable for use in the compositions disclosed herein.

[0108] The carbohydrates used generally contain digestible carbohydrates in an amount of 75 to 100% of the carbohydrates. Carbohydrates can include monosaccharides, disaccharides, oligosaccharides, and polysaccharides, as well as mixtures thereof. Generally, oligosaccharides of glucose are used. Many of these are commercially available as maltodextrin (3 to 20 DE), or in the case of short-chain carbohydrates, as corn syrup (>20 DE). Indigestible carbohydrates, such as fructooligosaccharides, inulin, and galactooligosaccharides may also be included. These are generally present in an amount of 0.2 to 5%, preferably 0.2 to 4% of the composition. Fibers including insoluble fibers may also be included.

[0109] In one embodiment, the composition may further comprise a source of amino acids, amino acid precursors, or amino acid metabolites, or any combination of two or more thereof, preferably free amino acids, amino acid precursors, or amino acid metabolites.

[0110] In various embodiments, the protein source is provided in liquid or dry (powder) form, or a blend thereof.

[0111] The total protein in the composition is the sum of all proteins contributed by all protein-containing ingredients in the composition. The amount of whey protein in the composition is the sum of all whey proteins contributed by all whey protein-containing ingredients in the composition. For example, in an embodiment where the composition includes ingredients (such as MPC) containing both WPC or WPI (such as heat-denatured WPC or WPI) and whey and casein, the total whey protein in the composition is the sum of the total whey proteins present in WPC and / or WPI and MPC.

[0112] One or more of the protein raw materials, such as WPC, WPI or casein raw materials, or a liquid nutritional composition can be processed to reduce the lactose content. In various embodiments, the protein raw material or liquid nutritional composition is treated with an enzyme such as β-galactosidase or subjected to filtration to remove lactose. Suitable enzyme treatments and filtration procedures for reducing the lactose content will be apparent to those skilled in the art.

[0113] In various embodiments, the composition contains less than about 10, 9, 8, 7, 6, 5, 4, 3, 2, 1, 0.5%, or less than about 0.1% lactose.

[0114] Whey Exemplary whey proteins for use in the present invention include whey protein concentrate and whey protein isolate. Whey protein is recognized as a complete protein known for its excellent amino acid profile that provides all essential amino acids and has a high content of cysteine and leucine. Whey protein is also known for its ease of digestion.

[0115] WPC is rich in whey protein but also contains other components such as lipids, lactose, and in the case of cheese whey-based WPC, glycomacropeptide (GMP), i.e., a non-globular protein related to casein that cannot be denatured. Membrane filtration is generally used in the production of whey protein concentrate, and alternative production methods of WPC particularly suitable for application in the present invention are described herein.

[0116] Whey protein can be derived from any mammalian species such as, for example, cows, sheep, goats, horses, buffalos, and camels. Preferably, the whey protein is of bovine origin.

[0117] Exemplary methods for preparing WPC suitable for use in the present invention are described in PCT International Application No. PCT / NZ2007 / 000059 (published as WO2007 / 108709), PCT International Application No. PCT / NZ2010 / 000072 (published as WO2010 / 120199), and PCT International Application No. PCT / IB2012 / 056103 (published as WO2013 / 065014), each of which is incorporated herein by reference in its entirety.

[0118] In various embodiments, the whey protein can be prepared by a method comprising: a) providing an aqueous solution of WPC or WPI having a protein concentration of about 15 - 50% (w / v) at a pH of about 4.7 - 8.5; and b) subjecting the solution to heat treatment by heating the solution to above about 50 °C for a time sufficient to allow protein denaturation to occur, for example, under turbulent flow conditions having a Reynolds number of at least about 500.

[0119] Heat treatment is applied to the preparation of proteins such as WPC to impart the required denaturation and ensure that it is suspendable. Whey protein contains high levels of globular proteins that are sensitive to aggregation in the denatured state. The denaturation temperature of β - lactoglobulin is pH - dependent, and at pH 6.7, irreversible denaturation occurs when the protein is heated above 65 °C. This denaturation is thought to expose free thiol groups, which then initiate the formation of protein - protein disulfide bonds, leading to polymerization and the formation of aggregates. Other disulfide bridges and cysteine residues are thought to play a role in the polymerization reaction. α - lactalbumin also has a denaturation temperature of about 65 °C.

[0120] One exemplary method for producing substantially denatured whey protein is called microparticulation. Microparticulation is generally achieved by heat aggregation or acid precipitation and is often combined with high shear and high pressure conditions (Havea, Baldwin, & Carr, 2009). Microparticulated whey protein can be considered a combination of native protein and size-controlled soluble and insoluble protein aggregates. Aggregated particles have restricted interactions with each other because free thiol groups decrease during microparticulation. Thus, one important parameter related to the functional properties of microparticulated whey protein is the degree of protein denaturation in the product.

[0121] The size, shape, and density of protein aggregates are affected by many environmental and processing parameters, including temperature, heating rate, pressure, shear, pH, and ionic strength. Depending on the combination of these parameters, aggregates can form dense microparticles with a volume-weighted mean diameter D[4,3] and / or a surface-weighted mean diameter D[3,2] of less than about 10 μm. For example, microparticulated whey can be formed under specific ionic strength and shear conditions. These particles have a dense structure, low intrinsic viscosity, and low specific volume. Furthermore, for microparticulated whey produced under shear conditions, a relationship is known to exist between aggregate size and heating temperature.

[0122] Whey protein can be prepared from a mixture of WPC or from a mixture of proteins. In various embodiments, the protein is or includes whey protein concentrate (WPC) or whey protein isolate (WPI).

[0123] In some embodiments, the whey protein in the composition is provided by blending WPC and / or WPI with one or more ingredients including whey protein and non-whey protein. For example, in one embodiment, the whey protein is provided by WPC and / or WPI and MPC.

[0124] In certain embodiments, the whey protein raw material is produced by the processes specified by US6,767,575 (Huss & Spiegel), US2006 / 0204643 (Merrill et al.), US4,734,827 (Singer et al.), US5,494,696 (Holst et al.), PCT / NZ2010 / 000072 (published as WO2010 / 120199), EP0412590 and EP0347237 (Unilever). Since each method of making the whey protein raw material imparts different properties, those using the present invention should select the protein raw material to best suit those processes.

[0125] In certain embodiments, the whey protein raw material is heat-treated, substantially denatured whey protein, such as WPC or WPI, dried, and then rehydrated in the composition or its aqueous components. In certain embodiments, the heat-treated, substantially denatured WPC has at least 35%, at least 55%, such as at least 70% protein (on a moisture and fat-free basis), and in certain embodiments at least 80% protein.

[0126] The heat-treated, substantially denatured liquid WPC (without drying) can also be used with the same protein concentration characteristics as defined for the dried raw material.

[0127] In certain embodiments, the heat-treated, substantially denatured whey protein, such as WPC or WPI, is dried to less than 5% water content, or to a water activity level that facilitates storage of the dried raw material over several months without excessive degradation.

[0128] In certain exemplary embodiments, the whey protein source is available as a powder, preferably as WPC or WPI powder.

[0129] In certain embodiments, the heat-treated or denatured protein, e.g., WPC, contains less than 90% by weight protein. For example, the heat-treated or denatured protein contains at least 51% by weight protein, at least 70% in certain embodiments, at least 80% in certain embodiments, and at least 55% of all denaturable proteins are present in the denatured state.

[0130] In certain embodiments, the heat-treated or denatured protein, e.g., WPC, has a volume-weighted mean diameter D[4,3] and / or a surface-weighted mean diameter D[3,2] of less than about 10 μm. In various embodiments, the whey protein in the denatured state can include particles having a volume-weighted mean diameter D[4,3] and / or a surface-weighted mean diameter D[3,2] of less than about 10, 9.5, 9, 8.5, 8, 7.5, 7, 6.5, 6, 5.5, 5, 4.5, 4, 3.5, 3, 2.5, or 2 μm. In various preferred embodiments, the volume-weighted mean diameter D[4,3] and / or the surface-weighted mean diameter D[3,2] can be less than about 5 μm, or less than about 3 μm, or less than about 2 μm.

[0131] In various embodiments, the composition includes a whey protein ingredient, e.g., WPC or WPI, that has been treated to reduce the lactose concentration. For example, enzymatic treatment of the protein ingredient breaks down lactose into its monosaccharides galactose and glucose, providing advantages such as an increase in sweetness, thereby allowing the sugar content of the nutritional composition to be reduced. The use of low-lactose whey ingredients can also provide improved mouthfeel properties such as increased creaminess or mouse coating. Casein

[0132] As the casein for use in any of the compositions described herein, soluble casein in the form of non-micellar casein, micellar casein, non-micellar casein salts, α-casein, β-casein, κ-casein, casein fractions, α-casein fractions, β-casein fractions, κ-casein fractions, casein treated by ultra-high pressure (UHP), translucent casein, or any arbitrary combination of two or more thereof may be mentioned.

[0133] In various embodiments, the casein is micellar casein, non-micellar casein, or micellar and non-micellar casein.

[0134] Non-micellar casein results from the dissociation of casein micelles and yields smaller fractions or soluble casein. Raw materials containing non-micellar casein are well known in the art.

[0135] In various embodiments, the casein comprises or is provided by a raw material comprising milk protein isolate (MPI), milk protein concentrate (MPC), micellar casein isolate (MCI), micellar casein concentrate (MCC), the protein of sweetened condensed milk, skim milk, sweetened skim milk, non-fat dry milk, whole milk, whole milk powder, casein salts, total milk protein (TMP), milk co-precipitate, MPC or MPI modified to dissociate casein micelles, calcium chelated casein micelles, charge-modified casein, at least a part of calcium or phosphate or both calcium and phosphate replaced with sodium, potassium, zinc, magnesium, etc., or any combination of two or more thereof, such as casein raw materials like MPC or MPI, glycosylated casein, or any combination of two or more thereof.

[0136] In one embodiment, the casein comprises casein particles having a diameter of about 40, 50, 60, 70, 50, 90, 100, 110, 120, 130, 140, 150, 160, or 165 nm, and a useful range can be selected between any of these values (e.g., about 50 to about 165, about 50 to about 100, or about 50 to about 70 nm).

[0137] Total milk protein (TMP) and its milk co-precipitates contain whey protein and casein and can be prepared using any method known in the art such as the method described in US4376072. For example, TMP suitable for use in the present invention can be treated with an alkali using methods known in the art to solubilize the protein. Co-precipitates suitable for use in the present invention can be produced using methods known in the art as described by Hayes et al., 1969 (Australian Journal of Dairy Technology, June 1969). Since TMP and co-precipitates contain whey protein in a partially or fully denatured state, they can provide both casein and denatured whey protein present in the nutritional compositions described herein.

[0138] MPC is often described as a milk protein in terms of % dry matter (added to "MPC"). For example, MPC70 is MPC having 70% dry matter as a milk protein. Generally, MPC is prepared by a process of performing ultrafiltration to prepare either a casein-rich stream or a whey protein-rich stream. These streams can be blended to achieve the desired ratio of casein to whey protein. In another embodiment, the milk protein concentrate can be prepared by blending a skim milk stream with a whey protein concentrate stream prepared by ultrafiltration and treating either the skim milk stream or the combined stream by cation exchange and optionally concentrating or drying. MPC suitable for use herein can be prepared from a mixture of MPCs.

[0139] In one embodiment, the casein comprises or is provided by a calcium-reduced casein composition. Examples of calcium-reduced casein compositions suitable for use herein include those prepared by the methods described in International PCT Publication No. WO2001 / 041578 and International PCT Publication No. WO2004 / 057971, which are hereby incorporated by reference in their entirety.

[0140] Calcium-reduced MPC is MPC having a calcium content lower than that of the corresponding non-reduced MPC. These products generally have a lower content of other divalent cations, such as magnesium, than the corresponding non-reduced products. Preferably, the calcium-reduced MPC is dried to a water content of less than 5% or to a water activity level that facilitates the storage of the dry raw material over several months without excessive degradation. Preferred MPCs for use in the present invention have calcium that has been manipulated by a cation exchange process. The manufacture and use of these calcium-reduced MPCs have been previously disclosed in U.S. Patent No. 7,157,108, Published PCT Application No. WO2008 / 026940, and U.S. Patent Application Publication No. 2010 / 0021595. These documents are hereby incorporated by reference in their entirety into this specification.

[0141] Ultra-high pressure (UHP)-treated translucent casein is produced by subjecting a casein-containing composition to high-pressure treatment as described in International Patent Application No. WO2004 / 091309, which is hereby incorporated by reference in its entirety. Translucent casein can also be produced by cation exchange of skim milk, milk protein concentrate, or milk protein isolate using the methods described and exemplified in International Patent Application No. WO2001 / 041579, which is hereby incorporated by reference in its entirety.

[0142] The term "casein salt" refers to a chemical compound of casein and metal ions produced by acid precipitation of casein and subsequent resolubilization with alkali metals containing metal ions. Hydroxide solutions containing sodium ions, potassium ions, and magnesium ions are used to produce sodium caseinate, potassium caseinate, or magnesium caseinate. Descriptions of suitable casein salts and methods for manufacturing casein salts for use herein are described in Fox&McSweeney, 2003 and the Dairy Processing Handbook, 2003.

[0143] Non-milk proteins In various embodiments, the composition comprises one or more, two or more, or three or more non-milk proteins selected from the group consisting of algae, plant proteins, and animal proteins, and their hydrolyzed forms.

[0144] Suitable non-milk proteins for use in the compositions described herein include proteins that are soluble at a pH of about 6 to about 8 or proteins provided in a form that can be suspended in a solution. Suitable non-milk proteins include proteins that are soluble and do not form aggregates under acidic conditions such as those present in the upper gastrointestinal tract.

[0145] In one embodiment, the non-milk protein is at least partially hydrolyzed. In another embodiment, the non-milk protein is not hydrolyzed. In one embodiment, the composition comprises a blend of two or more non-milk proteins, at least one non-milk protein is at least partially hydrolyzed, and at least one non-milk protein is not hydrolyzed.

[0146] In one embodiment, the composition comprises soybean protein, rice protein, or pea protein. In another embodiment, the composition comprises soybean protein and pea protein.

[0147] 3. Characteristics of the composition For the purposes of this specification, viscosity is measured at 20 °C using a rheometer such as an Anton Paar device that uses a cup and bob assembly at a shear rate of 100 s -1 unless otherwise specified. Other methods for measuring or estimating viscosity are well known in the art and may be used as appropriate.

[0148] For the purposes of this specification, energy density is measured by calculating using the standard calorific value of the food component. Again, other methods for measuring or estimating energy density such as calorimetry are well known in the art and may be used as appropriate.

[0149] For the purposes of this specification, the mean particle size (characterized by D[4,3] or D[3,2] or both) is measured using a Malvern Mastersizer 2000 (Malvern Instruments Ltd, Worcs, UK) with a particle refractive index of 1.46 for emulsion-based beverages, 1.52 for powders in suspension, and 1.33 for solvents.

[0150] Methods for assessing protein concentration are well known in the art, for example, as the measurement of protein nitrogen by the Kjeldahl method. This method is based on nitrogen measurement, and the protein concentration is calculated by multiplying the total nitrogen result by the conversion factor of 6.38 for milk protein.

[0151] As used herein, the degree of hydrolysis of a protein refers to the percentage of peptide bonds in the protein that are cleaved. The degree of hydrolysis can be determined using methods including, but not limited to, reagent-based methods such as HPLC, SDS PAGE, and the o-phthalaldehyde (OPA) method. In the OPA method, OPA, a thiol reagent such as ethanediol or dithiothreitol, or a derivative thereof, is reacted with casein, and the thiol reagent binds to specific amino acids within the hydrolyzed protein. The amino acid to which the thiol is bound fluoresces strongly at 450 nm, and the fluorescence level is used as a quantitative measure of the degree of hydrolysis.

[0152] Methods for determining the degree of protein denaturation are well known in the art. One exemplary method used herein relies on HPLC (Elgar et al. (2000) J Chromatography A, 878, 183 - 196), and other suitable methods for use include utilizing the Agilent 2100 Bioanalyzer (Agilent Technologies, Inc. 2000, 2001 - 2007, Waldbronn, Germany) and microfluidic chips, as well as Agilent 2100 Expert software (e.g., Anema, (2009) International Dairy J, 19, 198 - 204), and methods that rely on polyacrylamide gel electrophoresis (e.g., Patel et al., (2007) Le Lait, 87, 251 - 268).

[0153] The powder can be characterized by measuring the remaining denaturable protein as a percentage of the total protein (TN × 6.38) according to the following formula:

[0154]

Number

[0155] The denaturable whey protein is measured as Σ (bovine serum albumin + α-lactalbumin + β-lactoglobulin + lactoferrin + immunoglobulin).

[0156] In the case of carefully manufactured cheese WPC80, the sum of the above components is generally 60 - 63% of TN, so the proportion of denatured denaturable protein can be estimated according to the following formula:

[0157]

Equation

[0158] The thermal stability or storage stability of the liquid composition includes having no gelation, sedimentation, or aggregation either immediately after heat treatment or after long-term storage at a temperature of about 25 °C for, for example, at least 2 months, 3 months, or preferably at least 6 months or 12 months.

[0159] Gelation of the liquid nutritional composition is considered to be a state change from liquid to soft to hard solid. Gelation can be evaluated visually and by touch. If the solution does not flow after heating, this is considered to be gelation.

[0160] To achieve the required sterility while maintaining fluidity, the protein needs to be stable under heat treatment conditions. The nutritional composition was found to be surprisingly stable to the required heat treatment in the pH range of 6 - 8.

[0161] Exemplary methods for evaluating the heat stability of milk are well known in the art. The heat coagulation time (HCT) method involves sealing a milk sample (1 - 2 mL) in a glass tube, which is clipped to a platform and placed in a silicon oil bath thermostatically controlled at 140°C at a defined rocking speed. The length of time elapsed from placing the container in the oil bath until visible aggregates form is defined as the HCT (Singh H & Creamer LK (1992), Determination of heat stability, In: Advanced Dairy Chemistry e.d. Fox PF Elsevier). Applicants, without wishing to be bound by any theory and based on their experience including that described herein, believe that liquid nutritional compositions having a heat coagulation time of less than 65 seconds have a high risk of extensive fouling and blocking in UHT heating devices, while liquid compositions having an HCT of 65 - 80 seconds have a potential risk of fouling. As described herein, liquid nutritional compositions having a heat coagulation time of greater than 80 seconds are stable to UHT heat treatment at 140°C for 5 seconds. Alternatively or additionally, samples that show coagulation 3 minutes after heating to 121°C in an oil bath have a high risk of gelling and aggregating in a retort can.

[0162] Liquid nutritional compositions either have a reduced degree of coagulation or no coagulation at all in the upper gastrointestinal tract or under gastric conditions. Digestion in the stomach begins by the release of low pH gastric juice. Introduction of proteins into the acidic environment of the stomach forms curds, which can slow down the digestive process and delay gastric emptying.

[0163] Exemplary methods for evaluating physical properties such as the setting of the composition under these conditions are the in vitro acidification method described in the examples herein and in Schnell, 2005 (Nicholas Schnell (2005) Gastric emptying and plasma glucose response in men following ingestion of milk from different species. Massey University, Palmerston North, New Zealand. Available online: “https: / / mro.massey.ac.nz / xmlui / bitstream / handle / 10179 / 12658 / 01_front.pdf?sequence=1&isAllowed=y”). In this method, simulated gastric fluid (SGF) is prepared and added to the liquid nutritional composition. Gelation of the composition indicates setting under upper gastrointestinal tract conditions.

[0164] 4. Manufacturing method An exemplary method for manufacturing the liquid nutritional composition of the present invention is described below and shown in FIG. 1. Suitable modifications to the method for achieving the liquid nutritional composition described herein will be apparent to those skilled in the art.

[0165] In one embodiment, the dried fat-free raw material (a dry blend of protein and carbohydrate) is dispersed in water and hydrated. In one embodiment, the raw material is hydrated for about 60 minutes. In one embodiment, the water is heated to a temperature of about 50° C. to assist in the hydration of the dry raw material. Optionally, an antifoaming agent is added. In one embodiment, a stabilizer blend is added. In one embodiment, the stabilizer is added to the water at 80° C. before being mixed.

[0166] The hydrated mixture is then vigorously mixed or emulsified with a lipid raw material, for example, one or more oils or an oil-surfactant blend. In one embodiment, the lipid raw material is combined with an emulsifier and / or a stabilizer.

[0167] In one embodiment, sugars (carbohydrates) and proteins are mixed to assist in the dispersion and solubilization of the proteins. The mixing of proteins and sugars (carbohydrates) is an exemplary method of dispersion and solubilization, but the mixing of proteins and lipids can also be used to improve dispersion and solubilization.

[0168] In one embodiment, one or more minerals, trace elements, and vitamins are added. A suitable premix of minerals, trace elements, and vitamins known in the art may be used.

[0169] The components of the composition of the present invention are generally homogenized to reduce the size of the fat droplets / oil droplets and form an oil-in-water emulsion, and then heat-treated.

[0170] The homogenization step used to form the stabilized food composition involves the application of shear force to reduce the droplet or particle size. In some embodiments, for example, high-shear agitation in a homogenizer or high-shear rotor-stator disperser can be used. In certain embodiments, the base of the recombined liquid nutritional composition has an average particle size of less than 20 μm, such as less than 10 μm, more particularly less than 2 μm, or in certain embodiments less than 1 μm, as classified by the surface-weighted mean particle size parameter D[3,2] and / or the volume-weighted mean diameter D[4,3].

[0171] In one embodiment, the homogenization of the nutritional composition is carried out before the final heat treatment or can be carried out as part of the heat treatment, including, for example, during an initial, partial, pre-heating, or post-heating step. In one exemplary embodiment, the composition is homogenized at 60 °C, 150 / 50 bar. In certain embodiments of the liquid nutritional composition, for example, the composition has an average surface-weighted particle size D[3,2] and / or volume-weighted mean diameter D[4,3] of about 0.3 μm to about 2 μm or about 0.5 μm to about 1.5 μm after heating and optionally after blending or homogenization. For example, the composition has an average particle size of about 1, 0.5, 0.4, or about 0.3 μm.

[0172] The pH of the composition is adjusted to a pH of about 6 to about 8 before heat treatment. In one embodiment, the pH is adjusted to a pH of about pH 6 to about pH 8 before homogenization. In another embodiment, the pH is adjusted to a pH of about pH 6 to about pH 8 after homogenization.

[0173] In various exemplary embodiments, the liquid composition, when heated, for example, when heat treated with an F0 value equivalent to at least 121 °C for 3 minutes, for example, when heated above 140 °C for 5 seconds or 6 seconds, has an average particle size that does not substantially increase. For example, the composition has an average particle size that does not increase by more than 4 times when heated above 140 °C for 5 seconds, and in certain examples, does not increase by more than 3 times, more than 2 times when heat treated with an F0 value equivalent to at least 121 °C for 3 minutes.

[0174] In an exemplary embodiment, the liquid composition has an average particle size that does not increase when heated at a temperature of about 135 °C to about 150 °C for about 0.1 to about 10 seconds, or at a temperature of about 121 °C to about 135 °C for about 7.5 seconds to about 3 minutes.

[0175] The liquid nutritional composition is subjected to heat treatment after being preferably prepared to achieve a composition with storage stability, and more preferably to achieve commercial sterilization. Commercial sterilization means the conditions achieved by applying sufficient heat, alone or in combination with other appropriate treatments, so that the product does not contain microorganisms that can grow under normal non-refrigerated conditions where the product is likely to be held during distribution and storage.

[0176] As will be understood by those skilled in the art, the lethal effect of high temperature on microorganisms depends on both temperature and holding time, and it is well known that as the temperature increases, the time required to kill the same number of microorganisms decreases. The time required to reduce the initial number of microorganisms by a specific amount at a specific temperature is generally referred to as the "F value". As described in Mullan, W.M.A. (2007) (Mullan, W.M.A., Calculator for determining the F value of a thermal process. [Online]. www.dairyscience.info / calculators-models / 134-f-value-thermal-process.html) and the references therein, the F value of a thermal process can be calculated by plotting the lethal rate against the process time, and the lethal rate can be calculated using the following equation (Stobo, 1973): Lethal rate = 10 (T-Tr) / z where T is the temperature at which the lethal rate is calculated, Tr is the reference temperature to which the equivalent lethal effect is compared, and z is the reciprocal of the slope of the thermal death curve for the target microorganism or spore (all values are in degrees Celsius).

[0177] Therefore, the F value can be used to represent the amount of heat introduced into a specific process. F0 is a measure of the lethal heat generated from a specified thermal process (usually measured at the point in the container where the lethal rate is lowest). This value is the lethal effect corresponding to the number of minutes at 121.1°C assuming instantaneous heating and cooling, and the z value is 10°C (https: / / www.foodsafety.govt.nz / elibrary / industry / further-processing-code / part-3.pdf). As described herein, the liquid nutrient composition of the present invention is generally subjected to a heat treatment step having an F0 value corresponding to at least 121°C for 3 minutes, most preferably an F0 value corresponding to at least 140°C for 5 seconds, but exhibits useful heat stability such as not forming a gel.

[0178] Various heat treatments of the liquid nutrient composition can be used. Ultra-high temperature (UHT) treatment is an example. Typical UHT conditions are 135 - 150 °C for 2 - 18 seconds, but longer periods, for example, 10 seconds, 15 seconds, 20 seconds or more are also possible. Another process used to ensure sterility is retort heat treatment, which is often 120 - 130 °C for 10 - 20 minutes. Examples of such heat treatments can have an F0 value far exceeding the minimum threshold. Other combinations of equivalent heat treatments are known and are applicable to the present invention provided that the requirements for microbial stability and sterility are properly observed. Non-thermal processes of other known techniques can be used in combination with heat treatment to inhibit the microbiological activity in the liquid nutrient composition, for example, microfiltration.

[0179] In one exemplary embodiment, the composition is UHT sterilized at 144 °C for about 6 seconds. In one embodiment, the composition is further homogenized at 150 / 50 bar after heat treatment.

[0180] In one exemplary embodiment, the composition is subjected to heat treatment (retort sterilization) at 121 °C for about 10 minutes.

[0181] In various embodiments, the heat treatment can include a heat treatment of 3 F0, for example, 121 °C for 185 seconds, 130 °C for 23 seconds, 135 °C for 7.4 seconds, 140 °C for 2.3 seconds, 145 °C for 0.73 seconds, or 150 °C for 0.23 seconds, a heat treatment of 6 F0, for example, 121 °C for 370 seconds, 130 °C for 46 seconds, 135 °C for 14.7 seconds, 140 °C for 4.6 seconds, 145 °C for 1.46 seconds, or 150 °C for 0.46 seconds, or a heat treatment of 19.5 F0, for example, 121 °C for 1200 seconds, 130 °C for 151 seconds, 135 °C for 47.6 seconds, 140 °C for 15.1 seconds, 145 °C for 4.76 seconds, or 150 °C for 1.51 seconds.

[0182] In one embodiment, the heat-treated liquid nutritional composition is filled and packaged.

[0183] In one embodiment, the heat-treated liquid composition is dried. In one embodiment, the heat-treated liquid composition is dried to produce a powder. Methods for drying such compositions are known to those skilled in the art, and suitable methods for use herein will be apparent to those skilled in the art. The low viscosity of the heat-treated liquid composition means that the composition can be evaporated to a higher solids content prior to spray drying without fouling, resulting in better energy efficiency and higher throughput.

[0184] 5. Use of the Liquid Nutritional Composition The liquid nutritional composition described herein has a high whey protein content. Whey protein has an excellent Protein Digestibility-Corrected Amino Acid Score (PDCAAS). It is not only naturally rich in essential amino acids and branched-chain amino acids, but also contains a disproportionately high amount of leucine, an amino acid thought to be important for stimulating muscle protein synthesis. This high level of leucine, along with its unique rapid digestion profile, allows whey protein to significantly stimulate muscle protein synthesis more than casein and / or soy protein in young adults or the elderly.

[0185] In various embodiments, the liquid nutritional composition is administered to a subject to maintain or increase muscle protein synthesis, maintain or increase muscle mass, prevent or reduce loss of muscle mass, maintain or increase growth, prevent or reduce muscle catabolism, prevent or treat cachexia, prevent or treat sarcopenia, increase glycogen resynthesis rate, regulate blood glucose level, increase insulin response to elevated blood glucose concentration, reduce satiety, reduce boredom, increase food intake, increase calorie intake, improve glucose metabolism, increase postoperative recovery rate, increase preoperative rehabilitation effect before surgery or chemotherapy, increase recovery rate after injury, increase recovery rate after exercise, increase sports performance, and / or provide nutrients.

Example

[0186] Example 1 This example describes the preparation and properties of the liquid nutritional composition of the present invention.

[0187] 1. Preparation of liquid nutritional composition A high-protein liquid nutritional composition was prepared as follows. Water was heated to 50 °C and an antifoaming agent was added. The protein and carbohydrate raw materials were dry-blended, added to water, and hydrated for at least 60 minutes. A blend of oil and emulsifier was added. A premix of minerals, trace elements, and vitamins was added and dissolved. The pH was adjusted to 6.8 using a potassium hydroxide solution, and the premix solution was homogenized at 60 °C, 150 / 50 bar. The homogenized mixture was UHT sterilized at 140 °C for 6 seconds. The composition of each formulation is shown in Table 1 below. All formulations were nutritionally complete with respect to vitamins and minerals. The milk protein concentrate 4882 was a calcium-reduced milk protein concentrate produced using the method described in PCT / NZ2011 / 000134 published as WO2012 / 008858. The whey protein concentrate 550 was a heat-denatured whey protein concentrate produced using the method described in PCT / NZ2010 / 00072 published as WO2010 / 120199. The whey protein concentrate 80 was a natural whey protein obtained by ultrafiltration of cheese whey. The milk protein concentrate and whey protein concentrate were available from Fonterra Co-operative Group Limited.

[0188]

Table 1

[0189] The nutritional composition of formulations A, B, and C, and formulation D, a commercially available formulation with a similar protein content, is set out in Table 2.

[0190]

Table 2

[0191] 2. Analysis of formulations No protein aggregation or gelation was observed in formulations A and B after UHT sterilization. Both sterilized formulations had a smooth mouthfeel.

[0192] Formulation C aggregated during UHT sterilization and extensively gelled. No further analysis was performed on formulation C.

[0193] Using a rotational viscometer, the viscosity of the formulations was measured at a shear rate of 100 s -1 at 20 °C.

[0194] The mean particle size (characterized by d[3,2]) was determined for formulations A and B by static light scattering using a Malvern particle size analyzer (Mastersizer 2000, Malvern Instruments Ltd, Malvern, United Kingdom).

[0195] To evaluate the properties of the formulations under conditions mimicking those of the upper gastrointestinal tract, the in vitro acidification method was used as described by Schnell (2005). Simulated gastric fluid (SGF) with enzymes was prepared by adding 150 mM NaCl to 1 M hydrochloric acid and adding 3 g of pepsin (porcine gastric mucosa, Sigma P7000) to this solution and stirring for 30 minutes before use. Samples (100 mL) of each liquid nutritional composition were added to 150 mL beakers and warmed to 37 °C in a water bath. SGF was added to the compositions with continuous stirring until the pH decreased to pH 3. The appearance of the mixtures was observed. The results are shown in Table 3.

[0196] The above analysis was performed after storing formulations A, B, and D at 25 °C for at least 4 months. The results are shown in Table 4. After storage, no creaming, sedimentation, or taste changes were observed or detected.

[0197]

Table 3

[0198]

Table 4

[0199] Example 2 This example describes the preparation and properties of a liquid nutritional composition. Exemplary nutritional formulations (Table 6) were prepared using either modified WPC powder (WPC550) or native whey powder (WPC392) as detailed in Table 5 and a liquid milk protein concentrate with 20% total solids and 18% protein.

[0200] A high-protein liquid nutritional composition was prepared as follows. Water was heated to 55 °C and an antifoaming agent was added. The liquid milk protein concentrate was added to the water. Whey protein concentrate powder was slowly added with stirring and hydrated for at least 60 minutes. After hydration, the solution was homogenized at 60 °C, 150 / 50 bar. The time for visual aggregation of each formulation at 121 °C was determined. The homogenized mixture was then retort sterilized at 121 °C for 3 minutes.

[0201] For formulations A1, A2, A3, A4, A5 after retort sterilization, no protein aggregation or gelation was observed. All sterilized formulations had a smooth mouthfeel. Using a rotational viscometer, the viscosity of the retort formulations at a shear rate of 100 s -1 at 20 °C was measured (Table 7). The average particle size of the formulations (characterized by d[3,2] and d[4,3]) before and after retort sterilization was determined by static light scattering using a Malvern particle size analyzer (Mastersizer 2000, Malvern Instruments Ltd, Malvern, United Kingdom) (Table 7).

[0202] The particle sizes of the liquid nutritional compositions prepared using native whey (formulations B1 - 6), modified whey (formulations A1 - 5), and the liquid nutritional composition prepared after retort treatment of A5 are shown in Figure 2.

[0203]

Table 5

[0204]

Table 6

[0205]

Table 7

[0206] Results As shown in Table 7, the formulations containing modified WPC (WPC550) showed excellent thermal stability compared to native WPC (392). These results indicate that liquid nutritional formulations containing very high levels of protein (A1 - 5, even 20% protein) are thermally stable after heat treatment at a F0 value of 3 (121 °C for 3 minutes), while all formulations containing the same amount of unmodified native whey (WPC392) formed gels after retort processing at the same heat treatment of F0 value of 3 (121 °C for 3 minutes). Figure 2 shows that the liquid nutritional compositions containing modified whey proteins (A1 - 5) had an average particle size of approximately 3 μm characterized by d[4,3] before heat treatment and the average particle size did not change even after retort processing with a total protein content of 20%. In contrast, the liquid nutritional compositions containing native whey proteins (B1 - 6) had an average particle size of approximately 0.2 μm characterized by d[4,3] before heat treatment and these formed gels even after retort processing with a total protein content of 10%.

[0207] Example 3 Following the method of Figure 1, as shown in Table 8, 1.5 kcal / mL liquid nutritional formulations containing 6% total protein were prepared. Whey protein and non - whey protein (casein) were present in all liquid nutritional compositions at a weight ratio of 60:40. The whey protein was provided by raw materials either with modified WPC (WPC550) or native WPC (WPC392). The pH of all formulations was adjusted to pH 6.8.

[0208] The levels of minerals (sodium, potassium, calcium, magnesium) in the final compositions were identical at the same concentrations for Formulations A and B, and a higher magnesium level was applied for Formulation C (Table 9). These levels were selected according to the European Commission guidelines for the Food for Special Medical Purposes (FSMP) Directive.

[0209] A high-protein liquid nutritional composition was prepared as follows. Water was heated to 50 °C and an antifoaming agent was added. The protein and carbohydrate raw materials were dry-blended, added to the water, and hydrated for at least 60 minutes. A blend of oil and emulsifier was added. A premix of minerals, trace elements, and vitamins was added and dissolved. The pH was adjusted to 6.8 using a potassium hydroxide solution, and the premix solution was homogenized at 60 °C, 150 / 50 bar. Each homogenized mixture was then heat-sterilized using the retort process described in Table 8 below. The milk protein concentrate 4882 was a calcium-reduced milk protein concentrate manufactured using the method described in PCT / NZ2011 / 000134 published as WO2012 / 008858. The whey protein concentrate 550 was a heat-denatured whey protein concentrate manufactured using the method described in PCT / NZ2010 / 00072 published as WO2010 / 120199. The milk protein concentrate and the whey protein concentrate were available from Fonterra Co-operative Group Limited.

[0210] [Table 8]

[0211] [Table 9]

[0212] Results These results indicate that the liquid nutritional formulation containing native WPC (Formulation A) is not heat-stable at 6% total protein (ratio of whey to casein 60:40) after heat treatment with an F0 value of 3 (Table 10). Formulations containing modified WPC (Formulations B and C) showed excellent heat stability even after heat treatment with an F0 value of 6.

[0213] It is well known in the art that soluble divalent ions promote the aggregation of whey proteins and cause gelation by forming cross-linking reactions between whey protein molecules. The formulation containing twice the amount of soluble magnesium (provided by magnesium chloride) in the final formulation (Formulation C) remained stable after heat treatment with an F0 value of 6.

[0214] [Table 10]

[0215] Example 4 A high-protein liquid nutritional composition was prepared as follows. Water was heated to 50°C and an antifoaming agent was added. The protein and carbohydrate raw materials were dry-blended, added to water, and hydrated for at least 60 minutes. A blend of oil and emulsifier was added. A premix of minerals, trace elements, and vitamins was added and dissolved. The pH was adjusted to 6.8 using a potassium hydroxide solution, and the premix solution was homogenized at 60°C, 150 / 50 bar.

[0216] The compositions of the respective complexes are shown in Table 11 below. The milk protein concentrate 4882 was a calcium-reduced milk protein concentrate produced using the method described in PCT / NZ2011 / 000134, published as WO2012 / 008858. The milk protein concentrate 4861 was a calcium-reduced milk protein concentrate produced using the method described in PCT / NZ2011 / 000134, published as WO2012 / 008858. The whey protein concentrate 550 was a heat-denatured whey protein concentrate produced using the method described in PCT / NZ2010 / 00072, published as WO2010 / 120199. The milk protein concentrate and the whey protein concentrate were available from Fonterra Co-operative Group Limited.

[0217] Each homogenized mixture was heat-sterilized as described in Table 8.

[0218]

Table 11-1

[0219]

Table 11-2

[0220] The nutritional compositions and types of heat treatment of Complexes A, B, C, D, E, F, G, H are described in Table 12.

[0221]

Table 12

[0222] No protein aggregation or gelation was observed in Complexes A, B, C, D, E, F, G, H after heat sterilization. All of the sterilized complexes had a smooth mouthfeel.

[0223] Using a rotational viscometer, at 20 °C for 100 s -1The viscosity of the formulation at the shear rate was measured (Table 13). The average particle size (characterized by d[3,2] and d[4,3]) was determined for Formulations A and B by static light scattering using a Malvern particle size analyzer (Mastersizer 2000, Malvern Instruments Ltd, Malvern, United Kingdom) (Table 13).

[0224] The above analysis was carried out after storage at 25 °C for at least 6 months. After storage, no creaming, sedimentation, or change in taste was observed.

[0225]

Table 13

[0226] Example 5 To evaluate the properties of the formulation under conditions mimicking those of the upper gastrointestinal tract, the in vitro acidification method was used as described by Schnell (2005).

[0227] For comparison, three liquid nutritional compositions (A, B, E) described in Example 3 and three commercially available liquid nutritional compositions (Com1, Com2, Com3) described in Table 14 were selected.

[0228] Simulated gastric fluid (SGF) containing enzymes was prepared by adding 150 mM of NaCl to 1 M hydrochloric acid and adding 3 g of pepsin (porcine gastric mucosa, Sigma P7000) to this solution and stirring for 30 minutes before use. A sample (100 mL) of each liquid nutritional composition was added to a 150 mL beaker and warmed to 37 °C in a water bath. SGF was added to the composition with continuous stirring until the pH decreased to pH < 3. The appearance of the mixture was observed. The results are shown in Table 14.

[0229]

Table 14

[0230] Method of in vitro digestion test: The Human Gastric Simulator (HGS) developed by Kong and Singh (2010) was used as the in vitro digestion model. 150 mL of liquid nutrient compositions (A, B, E, Com1, Com2, Com3) were mixed with 19.2 mL of simulated gastric fluid (SGF) and 4.8 mL of enzyme solution (16 mg / mL of pepsin and 2 mg / mL of amamo lipase A) before being sent to the HGS. After warming to 37 °C, the nutrient compositions began to be digested by the enzymes, and the SGF was pumped at flow rates of 0.6 and 2.4 mL per minute, respectively. To accurately control gastric content excretion, digestive samples (60 mL) were taken out from the HGS every 20 minutes and adjusted to a gastric content excretion rate of 3.0 mL / min. The contraction frequency was 3 times / min, simulating the actual contractions of the stomach. The temperature of the HGS was maintained at 37 °C by a heater and a thermostat. The maximum digestion time was 220 minutes.

[0231] At each time interval, samples were taken out from the HGS for further analysis, then filtered through a mesh with a pore diameter of 1 mm, discharging only solid masses with a size less than 1 mm. Further, an experiment was conducted as a control without adding pepsin (only SGF) to observe the effect of only mechanical treatment on digestion. The pH and weight measurements for clot observation were carried out immediately before pepsin inactivation. pH measurement

[0232] The initial pH in the HGS was defined as the pH of the nutrient composition. Due to SGF intake (2.4 mL / min) and gastric content excretion (3 mL / min), the pH in the HGS at different times was assumed to be the pH of the excreted digestive samples collected every 20 minutes. Weight of clot

[0233] After digestion times of 20, 60, 120, and 220 minutes, the curd (if present) was collected, passed through a filter with a pore size of 1 mm to separate the clot and the aqueous phase. The clot was then rinsed with SGF to remove pepsin from the surface and immediately weighed (Table 15). It was then heated to 90 °C for 3 minutes to inactivate the pepsin. Images of the curd were obtained from 150 mL of a commercially available liquid nutritional composition after 20, 60, 120, and 220 minutes of digestion in the human gastric simulator (not shown). No curd was formed for any of the liquid nutritional compositions of the present invention at any point during digestion.

[0234] Determination of the average droplet diameter The average particle size and particle size distribution of samples obtained from the HGS were measured during digestion using a Malvern MasterSizer 2000 (Malvern Instruments Ltd., Malvern, Worcestershire, UK). The particle size of the digested samples was characterized using the surface mean diameter [d 3,2 (μm)] or the volume-surface mean diameter [d 4,3 (μm)].

[0235] Results of in vitro digestion: Digesta excreted from all liquid nutritional compositions with different protein contents (6, 9.6, and 14.4%) and compositions showed a similar rate of pH decrease from about 6.8 to below pH 3 over a 220-minute digestion period. Thus, the differences observed in the digestion behavior of the liquid nutritional compositions are not due to the rate of pH decrease but are related to the protein composition.

[0236] [Table 15]

[0237] For all commercially available liquid nutritional compositions containing casein as the main protein source (at least 80% w / w protein derived from casein), protein coagulation was evident within the first 20 minutes of digestion and remained distinct until the end of the digestion time. For any of the liquid nutritional compositions developed using the present invention, no curd formation was observed. Compositions A, B, and E remain in the liquid phase under adult gastric conditions. Since curds behave like solids in the stomach, the coagulated protein can delay gastric emptying. This example shows that the liquid nutritional compositions of the present invention can leave the stomach more quickly.

[0238] The change in the average particle size (d 3,2 ) of liquid nutritional composition samples under dynamic digestion in HGS is shown in Figure 3. The particle sizes of three commercially available liquid nutritional compositions containing casein as the main protein source (at least 80% w / w protein derived from casein) showed a significant increase in particle size during digestion. This increase in particle size indicates protein aggregation and oil droplet floc formation due to low pH and / or enzymatic action. In contrast, Compositions A, B, and E showed little change in particle size throughout the digestion time.

[0239] All documents referred to herein, including but not limited to patents, patent applications, journal articles, books, etc., are hereby incorporated by reference in their entirety. The section headings used herein are for organizational purposes only and should not be construed as limiting the subject matter being described.

[0240] Although the present invention has been described by way of example and with reference to specific embodiments, it is to be understood that modifications and / or improvements can be made without departing from the scope or spirit of the invention.

[0241] Industrial Applicability The liquid nutritional composition described in this specification is useful for providing nutrition to a subject in need thereof. Uses of the liquid nutritional composition include medical foods, enteral nutrition, foods for special medical purposes, liquid meal replacements, and nutritional supplements.

Claims

**Claim 1** A heat - treated storage - stable liquid nutritional composition having a pH of from about 6.0 to about 8.0, comprising at least about 6 g of total protein content per 100 mL of the composition, wherein the total protein content a) comprises or is provided by a raw material containing a heat - denaturable protein with at least about 55% present in a denatured state, and whey protein, b) comprises or consists of casein, or one or more non - milk proteins, or casein and one or more non - milk proteins, non - whey proteins, wherein the whey protein has a degree of hydrolysis of less than about 4%, and the whey protein and the non - whey proteins are present in a weight ratio of at least about 35:65, a liquid nutritional composition. **Claim 2** The liquid nutritional composition according to claim 1, wherein the total protein content of the composition comprises at least about 9 g of protein per 100 mL of the composition. **Claim 3** The liquid nutritional composition according to claim 1, wherein the total protein content of the composition comprises at least about 10 g of protein per 100 mL of the composition. **Claim 4** The liquid nutritional composition according to claim 1, wherein the total protein content of the composition comprises at least about 12 g of protein per 100 mL of the composition. **Claim 5** The liquid nutritional composition according to any one of claims 1 - 4, wherein the composition comprises an energy density of at least about 200 kcal per 100 mL of the composition. **Claim 6** The liquid nutritional composition according to any one of claims 1 - 5, wherein the composition comprises less than about 4 g per 100 mL of the composition of disaccharides, oligosaccharides, and / or polysaccharides containing or not containing one glucose unit. **Claim 7** The liquid nutritional composition according to any one of claims 1 - 6, wherein the denatured - state whey protein comprises microparticles having a volume - weighted average diameter D[4,3] of less than about 10 μm. **Claim 8** The liquid nutritional composition according to any one of claims 1 - 7, wherein the whey protein accounts for at least about 35 wt% of the total protein. **Claim 9** The liquid nutritional composition according to any one of claims 1 - 8, wherein the composition comprises at least about 5 g of whey protein per 100 mL of the composition. **Claim 10** The liquid nutritional composition according to any one of claims 1 - 9, wherein the whey protein is not hydrolyzed.

11. The liquid nutritional composition according to any one of claims 1 to 10, wherein the whey protein comprises a raw material containing a heat-denaturable protein at least about 65% of which is in a denatured state, or is provided thereby.

12. The liquid nutritional composition according to any one of claims 1 to 11, wherein the non-whey protein comprises or consists of casein.

13. The liquid nutritional composition according to any one of claims 1 to 12, wherein the casein comprises a raw material containing non-micellar casein, micellar casein, or a raw material containing non-micellar and micellar casein, or is provided thereby.

14. The casein is milk protein isolate (MPI), milk protein concentrate (MPC), micellar casein isolate (MCI), micellar casein concentrate (MCC), protein of sweetened condensed milk, skim milk, skim milk powder, sweetened skim milk, whole milk, whole milk powder, casein salt, total milk protein (TMP), milk coprecipitate, MPC or MPI modified to dissociate casein micelles, calcium chelated casein micelles, charge-modified casein, at least a part of calcium or phosphate or both calcium and phosphate replaced with sodium, potassium, zinc, magnesium, etc., or a combination of any two or more thereof, such as casein raw materials like MPC or MPI, glycosylated casein, or a combination of any two or more thereof, and the liquid nutritional composition according to any one of claims 1 to 13, wherein the composition comprises a raw material containing the same or is provided thereby.

15. The liquid nutritional composition according to claim 14, wherein the casein salt comprises sodium caseinate, calcium caseinate, magnesium caseinate, potassium caseinate, or a combination of any two or more thereof.

16. The liquid nutritional composition according to any one of claims 1 to 15, wherein the non-milk protein comprises a plant protein or a hydrolyzed plant protein.

17. The liquid nutritional composition according to claim 16, wherein the plant protein or hydrolyzed plant protein comprises the protein of canola, pea, chickpea, bean, mung bean, lentil, soybean, rice, wheat, sorghum, corn, maize, barley, almond, cashew, chia, flax, or hemp (cannabis), a hydrolyzed form thereof, or a combination of any two or more thereof.

18. The liquid nutritional composition according to any one of claims 1 to 17, wherein the composition comprises about 0.01 to about 10 g of non-milk protein per 100 mL of the composition.

19. The liquid nutritional composition according to any one of claims 1 to 18, wherein casein accounts for about 5 wt% to about 65 wt% of the total protein.

20. The liquid nutritional composition according to any one of claims 1 to 19, wherein the composition comprises about 0.01 to about 25 g of lipid per 100 mL of the composition.

21. The liquid nutritional composition according to any one of claims 1 to 20, wherein the composition comprises about 0.01 to about 45 g of carbohydrate per 100 mL of the composition.

22. The liquid nutritional composition according to any one of claims 1 to 21, wherein the composition has an energy density of about 50 to about 400 kcal per 100 mL of the composition.

23. The composition exhibits substantially no gelation or aggregation when subjected to heat treatment at a temperature of at least 3 F 0 The liquid nutritional composition according to any one of claims 1 to 22.

24. The composition has a viscosity of less than about 500 mPa·s when measured at a temperature of 20°C and a shear rate of 100 s -1 The liquid nutritional composition according to any one of claims 1 to 23.

25. The liquid nutritional composition according to any one of claims 1 to 24, wherein the composition has an average particle size of less than about 20 μm when classified by the surface weighted average particle size parameter d[3,2] and / or the volume weighted average diameter D[4,3].

26. The liquid nutritional composition according to any one of claims 1 to 25, wherein the protein in the composition remains soluble or does not form a coagulum at a pH of about 1 to about 5.

27. The viscosity of the composition increases by less than about 100% when measured at a temperature of 20°C and a shear rate of 100 s -1 after storage at a temperature of 25°C for at least three months, the liquid nutritional composition according to any one of claims 1 to 26.

28. The liquid nutritional composition according to any one of claims 1 to 27, wherein the composition does not exhibit observable gelation or observable aggregation or both after storage at a temperature of 25°C for at least 3 months.

29. The liquid nutritional composition according to any one of claims 1 to 28, wherein the composition has an average particle size of less than about 20 μm when classified by the surface weighted average particle size parameter d[3,2] and / or the volume weighted average diameter D[4,3] after storage at a temperature of 25°C for at least 3 months.

30. A method for preparing a heat - treated liquid nutritional composition, comprising: a) providing a liquid composition having a pH of 6.0 to 8.0, said composition comprising at least about 6 g of total protein content per 100 mL of said composition, said total protein content comprising i) whey protein, comprising or provided by a raw material containing at least about 55% of heat - denaturable protein present in a denatured state, and ii) non - whey protein, comprising or consisting of casein, or one or more non - milk proteins, or casein and one or more non - milk proteins, b) subjecting the liquid composition to a heat treatment at least 3 F 0 values to prepare a heat-treated liquid nutritional composition, and a method comprising:

31. wherein said heat - treated liquid nutritional composition a) having a viscosity of less than about 500 mPa·s when measured at 20 °C and a shear rate of 100 s -1 -1, or b) has an average particle size of less than about 20 μm when classified by surface - weighted mean particle size parameter d[3,2] and / or volume - weighted mean diameter D[4,3], c) does not substantially exhibit observable gelation or aggregation, or d) exhibits any combination of two or more of the above (a) - (c), the method according to claim 30.

32. The heat treatment has an F value equal to or greater than at least 3 0 The method according to claim 30 or 31

33. The method according to any one of claims 30 - 32, further comprising drying said heat - treated liquid nutritional composition.

34. The method according to any one of claims 30 - 33, wherein said liquid composition comprises the composition according to any one of claims 1 - 29.

35. A heat - treated liquid nutritional composition prepared by the method according to any one of claims 30 - 34.

36. A method for maintaining or increasing muscle protein synthesis, maintaining or increasing muscle mass, preventing or reducing loss of muscle mass, maintaining or increasing growth, preventing or reducing muscle catabolism, preventing or treating cachexia, preventing or treating sarcopenia, increasing glycogen resynthesis rate, regulating blood glucose level, increasing insulin response to an increase in blood glucose concentration, reducing satiety, reducing boredom, reducing food intake, reducing calorie intake, improving glucose metabolism, increasing the recovery rate after surgery, increasing the pre - rehabilitation effect before surgery or chemotherapy, increasing the recovery rate after injury, increasing the recovery rate after exercise, increasing sports performance, and / or providing nutrients to a subject in need thereof, comprising administering a liquid nutritional composition according to any one of claims 1 - 29 to the subject.

37. Use of the liquid nutritional composition according to any one of claims 1 to 29 in the preparation of a composition for maintaining or increasing muscle protein synthesis, maintaining or increasing muscle mass, preventing or reducing loss of muscle mass, maintaining or increasing growth, preventing or reducing muscle catabolism, preventing or treating cachexia, preventing or treating sarcopenia, increasing the rate of glycogen resynthesis, regulating blood glucose levels, increasing the insulin response to an increase in blood glucose concentration, reducing satiety, reducing boredom, reducing food intake, reducing calorie intake, improving glucose metabolism, increasing the rate of recovery after surgery, increasing the prehabilitation effect before surgery or chemotherapy, increasing the rate of recovery after injury, increasing the rate of recovery after exercise, increasing sports performance, and / or providing nutrients to a subject in need thereof.

38. A liquid nutritional composition according to any one of claims 1 to 29 for maintaining or increasing muscle protein synthesis, maintaining or increasing muscle mass, preventing or reducing loss of muscle mass, maintaining or increasing growth, preventing or reducing muscle catabolism, preventing or treating cachexia, preventing or treating sarcopenia, increasing the rate of glycogen resynthesis, regulating blood glucose levels, increasing the insulin response to an increase in blood glucose concentration, reducing satiety, reducing boredom, reducing food intake, reducing calorie intake, improving glucose metabolism, increasing the rate of recovery after surgery, increasing the prehabilitation effect before surgery or chemotherapy, increasing the rate of recovery after injury, increasing the rate of recovery after exercise, increasing sports performance, and / or providing nutrients to a subject in need thereof.

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