Methods, devices and compositions for preserving human milk

Abstract

Described herein are compositions and methods for preserving human milk, preventing rancidity in human milk, extending the shelf life of human milk, and maintaining the nutritional properties of human milk. Specifically, the disclosure includes storage devices for preserved human milk, and methods and compositions for preserving the same.

Description

[Technical Field]

[0001] (Reference to Related Application) This application claims priority to U.S. Provisional Application No. 63 / 445,776, filed February 15, 2023, and U.S. Provisional Application No. 63 / 507,325, filed June 9, 2023, the entire contents of each of which are incorporated herein by reference.

[0002] Described herein are compositions and methods for preserving human milk, preventing oxidation of human milk, extending the shelf life of human milk, and maintaining the nutritional properties of human milk. Specifically, the disclosure includes, but is not limited to, storage devices for preserved human milk, and methods and compositions for preserving the same. [Background technology]

[0003] The following description of the background of the present technology is provided merely as a reference for understanding the present technology and does not constitute prior art of the present technology.

[0004] Established guidelines for infant feeding recommend that infants be fed nothing but human milk during the first six months of life; that is, no other foods or water should be given to infants during that time. This makes human milk the only recommended source of calories for the critical period of life. If necessary, human milk can be supplemented or replaced with infant formula.

[0005] For practical reasons, nursing parents express, store, and freeze excess human milk. This milk is then thawed and used. However, human milk often becomes rancid after storage, resulting in an unpleasant taste and odor for infants. Furthermore, frozen and thawed human milk is vulnerable to deterioration and rancidity. This occurs because freezers are unable to preserve the complex emulsified structure of human milk, causing the breakdown of fats and the production of rancid substances. Rancid human milk has an unpleasant odor and taste, which can cause newborns and infants to refuse to consume it and discontinue breastfeeding.

[0006] This issue is of significant concern to parents and healthcare professionals because it forces inappropriate or undesirable feeding practices (i.e., relying on commercially available formula, which is a nutritionally inferior substitute for human milk). Lipid oxidation leads to the formation of free fatty acids in expressed human milk, which increase during storage. This leads to rancidity, shortened shelf life, and ultimately to malnutrition in infants. Oxidants and lipolytic proteins (lipases) are substances that break down the lipids in human milk and convert them into free fatty acids. Because the exact chemical composition of human milk, particularly the amount and activity of oxidants and lipases, varies between individuals and over time within the same individual, it is difficult to predict when human milk stored in a home environment will become rancid. Furthermore, there is currently no method to reverse rancidity after human milk has become rancid, nor is there a reliable solution to prevent spoilage without requiring sophisticated equipment and expertise (ultra-high-temperature pasteurization). Summary of the Invention [Problem to be solved by the invention]

[0007] The disclosed approach offers parents / donors a solution to the above problems using a safe, effective, and universally applicable formulation that is exposed to human milk during or after expression and eliminates or inhibits the processes that cause rancidity, thereby extending shelf life and preserving the nutritional value of human milk during storage. Additionally, the formulations and methods disclosed herein maintain the structural integrity of human milk upon freezing and thawing, preventing fat breakdown and rancidity.

[0008] Examples of the disclosed approach are disclosed below. One example process involves adding existing food-safe ingredients to expressed human milk that provide antioxidant protection, extend shelf life, and maintain the nutritional properties of the exposed human milk during storage. An example composition of matter is a mixture of ingredients that is exposed to the expressed human milk. An example device is a breathable device that acts as an embedding material, filter, or capsule and includes an antioxidant that contacts the expressed human milk during collection and / or in a storage container.

[0009] In particular, the disclosed approach can be used to extend the shelf life, flavor, and nutritional value of expressed human milk without the need for ultra-high temperature pasteurization.

[0010] More specifically, approximately 50% of infants in the United States are exclusively breastfed until 3 months of age, and half of these (25% of the total) continue to be exclusively breastfed until 6 months of age (in accordance with WHO and UNICEF recommendations). Human milk is the only source of nutrition for many infants for several months, and ensuring adequate access to nutritious human milk is essential for their ability to achieve the most critical developmental milestones in early life. Human milk oligosaccharides (HMOs) are essential nutrients found only in expressed human milk, which cannot be obtained or synthesized by other mammals. Human milk is the gold standard for infant nutrition. In today's work-life balance, nursing mothers return to work when their infants require human milk. Therefore, nursing mothers use breast pumps to express milk and store it in disposable frozen storage bags for later thawing. Currently, freezers available in ordinary households (which can cool to -20°C) cannot adequately preserve the complex emulsion structure of human milk, and thawed human milk often develops a rancid odor, causing some infants to reject it. Currently, the only way to prevent expressed human milk from going rancid is to use ultra-high temperature sterilization, which changes its nutritional content and functionality, but this is not practical to perform at home.

[0011] Therefore, there is an urgent and widespread need to prevent / slow / inhibit oxidation of expressed human milk while maintaining its safety and nutritional value. The disclosed approach solves this problem by providing a method to slow or stop oxidation, extend shelf life, and preserve the nutritional properties of human milk. This method can be performed without the need for pasteurization.

[0012] The oxidation prevention method is described in "Lipase Inhibitors for Preventing Oxidation of Expressed Human Milk During Storage (U.S. Published Patent Application No. 2020 / 0323225 A1, published October 15, 2020)" and "Method for Preventing Oxidation, Extending Shelf Life, and Preserving Nutritional Value of Expressed Human Milk During Storage (U.S. Provisional Patent Application No. 63 / 445,776, filed February 15, 2023)," both of which are incorporated by reference herein in their entireties and are considered fully set forth herein. [Means for solving the problem]

[0013] In one aspect of the present invention, the present disclosure provides a composition comprising at least one active ingredient selected from at least one emulsifier, at least one antioxidant, at least one ice-structure-forming protein, at least one lipoprotein lipase (LPL) inhibitor protein, at least one small molecule lipase inhibitor, at least one milk-stabilizing protein, at least one glycosaminoglycan, at least one flavonoid, or a combination thereof.

[0014] In either embodiment, the emulsifier is a surfactant, a protein, and / or a nanoparticle that functions as an emulsifier.

[0015] In either embodiment, the surfactant is a polysorbate, a citrate ester of mono- and diglycerides, and / or a naturally occurring emulsifier.

[0016] In either embodiment, the naturally occurring emulsifier is lecithin and / or saponin-rich quillaja extract.

[0017] In either embodiment, the lecithin is derived from sunflower or soybean.

[0018] In either embodiment, the emulsifier is pectin.

[0019] In either embodiment, the pectin is poly-D-galacturonic acid methyl ester.

[0020] In any embodiment, the pectin is apple pectin, citrus pectin, beet pectin, okra pectin, or kiwifruit pectin.

[0021] In either embodiment, the pectin is apple pectin.

[0022] In either embodiment, the pectin is a low methoxy pectin or a high methoxy pectin.

[0023] In either embodiment, the pectin is a pectin subunit selected from galacturonic acid, digalacturonic acid, or trigalacturonic acid.

[0024] In any embodiment, the pectin is selected from GENU® Pectin Beta, GENU® Pectin LM-106 AS-YA, GENU® Pectin YM-100-L, Pacific RSND Pectin, Pacific LM-104 Pectin, or Pacific LM-12 Pectin.

[0025] In both embodiments, the pectin is Pacific LM-12 pectin.

[0026] In either embodiment, the amount of pectin ranges from about 0.03 mg / ml to about 20 mg / ml.

[0027] In any embodiment, the amount of pectin is in the range of about 0.034 mg to about 9000 mg.

[0028] In either embodiment, the surfactant is a non-ionic surfactant.

[0029] In any embodiment, the antioxidant is selected from vitamin C or a derivative thereof, vitamin E or a derivative thereof, a vitamin C-vitamin E mixture, ethylenediaminetetraacetic acid (EDTA) or a derivative thereof, phospholipids, egg yolk, or lambda-carrageenan.

[0030] In any embodiment, the at least one antioxidant is vitamin C, vitamin E, or vitamin A.

[0031] In all embodiments, the amount of vitamin C ranges from about 20.6 mg / ml to about 350 mg / ml.

[0032] In all embodiments, the amount of vitamin C is in the range of about 0.6 μg to about 101 mg.

[0033] In all embodiments, the amount of vitamin E ranges from about 0.01 mg / ml to about 150 mg / ml.

[0034] In either embodiment, the vitamin E is synthetic vitamin E in the range of about 0.01 μg to about 1.8 mg or natural vitamin E in the range of about 0.01 μg to about 2.682 mg.

[0035] In either embodiment, the lipoprotein lipase (LPL) inhibitor protein is angiopoietin-like protein (ANGPTL) 3, 4, and / or 8.

[0036] In either embodiment, the milk stabilizing protein is lactoperoxidase.

[0037] In any embodiment, the glycosaminoglycan is selected from glucosamine sulfate, chondroitin sulfate, hyaluronic acid, heparan sulfate, or fucoidan.

[0038] In any embodiment, the flavonoid is selected from ginkgetin, isoginkgetin, myricetin, luteolin, or epigallocatechin gallate.

[0039] In any embodiment, at least one active ingredient is not an antibody or protein that binds to lipoprotein lipase (LPL).

[0040] In any embodiment, at least one active ingredient is not a lipase inhibitor selected from GSK264220A, orlistat, RHC 80267, and Xen445.

[0041] In either embodiment, one or more of the active ingredients is not naturally found in human milk.

[0042] In either embodiment, the composition preserves human milk.

[0043] In another aspect, the present disclosure provides a composition for preserving human milk, the composition comprising: (a) pectin; (b) vitamin C; and (c) vitamin E.

[0044] In any embodiment, the composition of the present disclosure further comprises (a) from about 0.003% (w / v) to about 0.9% (w / v) pectin, (b) from about 0.034 mg to about 9 mg pectin, (c) from about 5 mg to about 1333 mg pectin, or (d) from about 34 mg to about 9000 mg pectin.

[0045] In any embodiment, the pectin is selected from beta pectin, GENU® Pectin Beta, GENU® Pectin LM-106 AS-YA, GENU® Pectin YM-100-L, Pacific RSND pectin, Pacific LM-104 pectin, or Pacific LM-12 pectin.

[0046] In either embodiment, the pectin is Pacific LM-12 pectin.

[0047] In any embodiment, the compositions disclosed herein further comprise (a) about 0.676 μg to about 101 μg of vitamin C, (b) about 0.1 mg to about 15 mg of vitamin C, or (c) about 0.676 mg to about 101 mg of vitamin C.

[0048] In any embodiment, the compositions disclosed herein further comprise (a) about 0.0122 μg to about 1.8 μg of vitamin E, (b) about 1.8 μg to about 270 μg of vitamin E, or (c) about 0.01 mg to about 1.8 mg of vitamin E, wherein the vitamin E is synthetic vitamin E.

[0049] In any embodiment, the compositions disclosed herein further comprise: (a) from about 0.0000271 IU to about 0.004 IU of vitamin E; (b) from about 0.004 IU to about 0.27 IU of vitamin E; or (c) from about 0.01 IU to about 2.68 IU of vitamin E.

[0050] In any embodiment, the compositions disclosed herein further contain lecithin.

[0051] In any embodiment, the compositions disclosed herein further comprise one or more of a disintegrant, an adsorbent, a colorant, a flavoring agent, a sweetener, or a dispersing agent.

[0052] In any embodiment, the compositions disclosed herein further comprise a binder.

[0053] In any embodiment, the compositions disclosed herein are prepared in the form of either a liquid concentrate, a tablet, a powder, or a single-use sachet.

[0054] In either embodiment, the compositions disclosed herein reduce lipase activity and preserve the antioxidant capacity of human milk.

[0055] In either embodiment, the compositions disclosed herein are used to prevent rancidity, extend shelf life, and / or maintain the nutritional properties of human milk during storage.

[0056] In another aspect, the present disclosure provides a method of preserving human milk, the method comprising contacting human milk with a composition described herein and storing the human milk.

[0057] In any embodiment, the methods of the disclosure include (a) contacting human milk with a composition comprising: (i) from about 0.034 mg / ml to about 9 mg / ml of pectin, (ii) from about 0.676 μg / ml to about 101 μg / ml of vitamin C, and (iii) from about 0.0182 μg / ml to about 2.68 μg / ml of natural vitamin E or from about 0.0122 μg / ml to about 1.8 μg / ml of synthetic vitamin E; and (b) storing the human milk.

[0058] In either embodiment, storing comprises freezing the human milk at about -20°C.

[0059] In either embodiment, storage is at about 4°C.

[0060] In any embodiment, storage is carried out for about 1 day to about 5 years.

[0061] In any embodiment, the human milk is about 1 ml to about 1000 ml.

[0062] In either embodiment, the human milk is about 1 ml.

[0063] In either embodiment, the human milk is about 5 ounces.

[0064] In either embodiment, the human milk is about 150 ml.

[0065] In either embodiment, the human milk is about 1000 ml.

[0066] In either embodiment, the human milk is expressed human milk or synthetic human milk.

[0067] In one embodiment, the present disclosure provides a device comprising a housing defining an interior volume of a space, the housing having at least one opening configured to allow a substance within the interior volume of the space to exit the housing and contact human milk or to contact human milk within the interior volume of the space, wherein the substance within the interior volume of the space comprises a composition disclosed herein.

[0068] In either embodiment, the device is configured to be placed within a human milk collection or storage container.

[0069] In either embodiment, the human milk collection or storage container is a bag.

[0070] In either embodiment, the device is configured to have an inlet and an outlet, and when the device is configured to be placed between the breast pump and the human milk storage container, this ensures that all human milk passes through the inlet and outlet before entering the human milk storage container.

[0071] In another aspect, the present disclosure provides a milk storage container having a composition disclosed herein immobilized on the interior surface of the container.

[0072] In either embodiment, the container is made of plastic.

[0073] In either embodiment, the pouch is configured to be stored at a temperature range of about -80°C to about 4°C or room temperature.

[0074] In either embodiment, the bag is configured for storage for between about 1 day and about 5 years.

[0075] In one aspect, the invention provides kits comprising the compositions disclosed herein and, optionally, instructions for use.

[0076] In either embodiment, the kit further comprises a device disclosed herein or a human milk storage container disclosed herein. [Brief explanation of the drawings]

[0077] Features, aspects, and advantages of the present disclosure will become apparent from the following description and from the non-limiting examples shown in the drawings.

[0078] Figure 1 shows the accumulation of glycerol, a by-product of lipolysis, in human milk samples stored at -20°C for different periods. Glycerol was detected by a glycerol-dependent luminescence reaction that measures the bioluminescence of each sample (lux; Y-axis). Samples were tested at different time points after storage, indicated on the X-axis, and compared to three control groups.

[0079] Figure 2 shows the results of lipase inhibition in human milk samples stored at -20°C for 1 week, based on screening of approximately 2,700 compounds from three different compound libraries (biologue phenotype microarray, food additive library, and food-derived compound library). Lipase was detected by a quenched BODIPY-fatty acid conjugate. RFU < 400 (dotted line) indicates lipase inhibition.

[0080] Figures 3A and 3B show lipase inhibition in human milk samples detected with quenched BODIPY-fatty acid conjugates from single compounds or combinations indicated on the x-axis. For all compounds except vitamin C and vitamin E, the rightmost bar in each compound series is 10 mg / ml (1% w / v), a two-fold dilution from each preceding bar. For vitamin C, the rightmost bar in each series is 350 μg / ml, a two-fold dilution from each preceding bar. For vitamin E, the rightmost bar in each series is 150 μg / ml, a two-fold dilution from each preceding bar (Figure 3A). Antioxidant capacity, shown as quantified absorbance over time (as indicated on the x-axis), was measured for fresh human milk, untreated stored milk, pectin-treated stored milk, and stored milk treated with a combination of sunflower lecithin, low-methoxy pectin, vitamin C, and vitamin E (Figure 3B). Figure 3B shows, at time 0, from highest to lowest vertical axis values: positive control, fresh human milk, stored milk treated with sunflower lecithin and pectin (low methoxy) and vitamins C / E, stored milk treated with pectin, untreated milk, and the negative control (absorbance 0).

[0081] Figure 4 shows the results of lipase inhibition in human milk samples detected with quenched BODIPY-fatty acid conjugates from single compounds or combinations indicated on the X-axis. For each series of compounds indicated on the X-axis, for all compounds except vitamin C and vitamin E, the rightmost bar in each series is 10 mg / ml (1% w / v) and is a two-fold dilution from each preceding bar. For vitamin C, the rightmost bar in each series is 350 μg / ml and is a two-fold dilution from each preceding bar. For vitamin E, the rightmost bar in each series is 150 μg / ml and is a two-fold dilution from each preceding bar.

[0082] Figure 5 shows the lipase inhibitory effects of BODIPY-fatty acid conjugates in human milk samples from 14 different donors stored with apple pectin (TUOTAI) plus vitamin C and vitamin E. Samples were treated with no formulation, followed by pectin at 0.06%, 0.13%, 0.25%, and 1%. Vitamin C was added at concentrations of 22 μg / ml, 44 μg / ml, 88 μg / ml, 176 μg / ml, and 352 μg / ml, and vitamin E was added at concentrations of 11 μg / ml, 22 μg / ml, 44 μg / ml, 88 μg / ml, and 176 μg / ml, respectively, from left to right.

[0083] Figures 6A, 6B, and 6C show lipase concentrations detected by BODIPY-fatty acid conjugates (Figure 6A), glycerol concentrations (displayed as bioluminescence) measured by a glycerol-dependent photoluminescence reaction (Figure 6B), and antioxidant capacity (Figure 6C) in archived human milk samples treated with locust bean gum, guar gum, purified guar gum, gum arabic, GENU® Pectin Beta, GENU® Pectin LM-106 AS-YA, GENU® Pectin YM-100-L, Pacific RSND pectin, Pacific LM-104 pectin, or Pacific LM-12 pectin.

[0084] Figures 7A, 7B, 7C, 7D, 7E, and 7F show the lipase concentrations detected by BODIPY-fatty acid conjugates (Figures 7A-7C) and the glycerol concentrations measured by a glycerol-dependent luminescence reaction (bioluminescence as an indicator) (Figures 7D-7F) in human milk samples after storage. Lipase production was measured in samples untreated (Figure 7A) or treated with 5 mg of Pacific LM-12 pectin + 0.1014 mg of vitamin C + 2.7 μg of vitamin E per ml of human milk after raw (RAW) or batch sterilization (BP), high-temperature short-time sterilization (HTST), ultra-high-temperature sterilization (UHT), or ultra-pasteurization (UP) (Figure 7B). The fold reduction in lipase activity between the treated and untreated groups was measured (Figure 7C). Glycerol concentrations in human milk samples were measured in samples that were unpasteurized (RAW) or sterilized by batch sterilization (BP), high-temperature short-time sterilization (HTST), ultra-high-temperature sterilization (UHT), or ultra-pasteurization (UP) and were either untreated (Figure 7D) or treated with 5 mg of Pacific LM-12 pectin + 0.1014 mg of vitamin C + 2.7 μg of vitamin E per ml of human milk (Figure 7E). The fold reduction in glycerol between treated and untreated samples was measured as shown in Figure 7F.

[0085] Figures 8A, 8B, 8C, 8D, 8E, and 8F show the lipase concentrations detected by BODIPY-fatty acid conjugates (Figures 8A-8C) and the glycerol concentrations detected by a glycerol-dependent photoluminescence reaction (displayed as bioluminescence) (Figures 8D-8F) in unpasteurized and unpasteurized human milk samples after storage. Lipase production was measured in unpasteurized and unpasteurized human milk samples left untreated (Figure 8A) or after treatment with 5 mg Pacific LM-12 pectin + 0.1014 mg vitamin C + 2.7 μg vitamin E per ml of milk (Figure 8B). The fold reduction in lipase activity between treated and untreated samples was also calculated (Figure 8C). Glycerol concentrations were measured in unpasteurized and unpasteurized human milk samples that were left untreated (Figure 8D) or after treatment with 5 mg Pacific LM-12 pectin + 0.1014 mg vitamin C + 2.7 μg vitamin E per ml of milk (Figure 8E). Glycerol concentrations were also calculated for treated and untreated samples (Figure 8F).

[0086] Figure 9 shows the antioxidant capacity (left) and lipase concentration (right) results for human milk samples collected from three different subjects. Samples were untreated or treated with 0.5% w / v (0.735 g) Pacific LM-12 pectin, 15 mg vitamin C + 0.6 IU (0.402 mg) vitamin E, or 0.5% w / v (0.735 g) Pacific LM-12 pectin + 15 mg vitamin C + 0.6 IU (0.402 mg) vitamin E per 5 oz of human milk, then frozen. Antioxidant capacity was measured by measuring the absorbance of each sample and reported as the average for each treatment group. Fresh milk from each subject was measured for antioxidant capacity without treatment. Lipase concentration was measured using a BODIPY-fatty acid complex and reported as the average for each treatment group.

[0087] Figure 10 shows the results of headspace analysis of 13 different human milk samples after storage, either left untreated or treated with 5 mg Pacific LM-12 pectin + 0.1014 mg vitamin C + 2.7 μg vitamin E per ml of human milk. Results are shown for rancidity volatiles (pivalic acid, pelargonic acid, capric acid, lauric acid) as Log(2) fold change between treated and untreated groups, as shown on the left y-axis.

[0088] Figure 11 shows the formulations compressed on an LFA VICE manual tablet press with 0.5% w / v (0.735 g) Pacific LM-12 pectin, 15 mg vitamin C, and 0.6 IU (0.402 mg) vitamin E per 5 oz of human milk. 1 indicates a 6 mm diameter and 1 mm thickness; 2 indicates a 6 mm diameter and 1.3 mm thickness; 3 indicates a 7.5 mm diameter and 0.5 mm thickness; and 4 indicates a 7.5 mm diameter and 1.3 mm thickness.

[0089] Figures 12A and 12B show illustrations of a vented capsule (Figure 12A) and a filter unit (Figure 12B). DETAILED DESCRIPTION OF THE INVENTION

[0090] (Detailed Description of the Invention) (definition) Embodiments of the present disclosure are described in more detail below. However, aspects of the present disclosure may be embodied in different forms and are not limited to the embodiments disclosed herein. Rather, these embodiments are provided for completeness purposes so that those skilled in the art can fully appreciate the scope of the invention. The terms used herein are for the purpose of describing particular examples and are not intended to be limiting.

[0091] Unless otherwise defined, all terms (including technical and scientific terms) used herein have the meanings commonly understood by those skilled in the art to which this specification pertains. Furthermore, it should be further understood that terms defined in common dictionaries should be interpreted in a manner consistent with the meaning in the context of this application and the related technical field, and should not be interpreted in an idealized or overly formal sense unless explicitly defined as such.

[0092] The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety.

[0093] The practice of the present technology will employ, unless otherwise indicated, conventional techniques in the fields of molecular biology, microbiology, chemical engineering, and cell biology, which are within the level of skill of one of ordinary skill in the art.

[0094] Unless the context dictates otherwise, it is specifically intended that the various features of the disclosure described herein can be used in any combination. Furthermore, the present disclosure also contemplates that, in some embodiments, any of the features disclosed herein or combinations thereof may be excluded or omitted. For example, for purposes of illustration, if the specification describes a composite as consisting of components A, B, and C (or A, B, and / or C), it is specifically intended that any or any combination of A, B, or C, singly or in any combination, be omitted or discarded.

[0095] Ranges involving numerical designations, e.g., pH, temperature, time, concentration, molecular weight, etc., are approximations that vary (+) or (-) by increments of 1.0 or 0.1, as appropriate, or alternatively include a range of variation of ±15%, or 10%, or 5%, or 2%. Unless expressly stated, all numerical designations are preceded by the term "about," which will be understood by those of ordinary skill in the art and will vary within certain ranges depending on the context, and in some contexts, the term will be interpreted to include any of the aforementioned variations. It should also be understood that, unless expressly stated, reagents described herein are merely exemplary, and that equivalents of such reagents are within the skill of those of ordinary skill in the art.

[0096] In this specification and the appended claims, the singular forms "a," "an," and "the" are to be construed as including the plural forms as well, unless the context clearly dictates otherwise.

[0097] Also, as used herein, "and / or" is intended to include all possible combinations involving one or more of the associated listed items, as well as the absence of a combination ("or") when interpreted alternatively.

[0098] As used herein, the term "about" is intended to vary to a certain extent depending on the context of use within the range understood by those skilled in the art. When it is not clearly understood by those skilled in the art from the context of use, "about" means within ±10% of the term in question.

[0099] As used herein, the terms "appropriate," "effective," or "sufficient" refer to the selection of any ingredient, range, dosage form, etc. disclosed herein, meaning that the ingredient, range, dosage form, etc. is suitable for the disclosed purpose.

[0100] As used herein, "emulsifying agent" or "emulsifier" refers to a chemical compound that makes two or more immiscible liquids mixable. Furthermore, emulsifiers maintain the stability of a mixture (i.e., a mixture of at least two components) and prevent the individual components from separating.

[0101] As used herein, "antioxidant" refers to a chemical compound that inhibits oxidative effects (i.e., chemical reactions that can generate free radicals), such as oxidation. In some embodiments, antioxidant activity may only be observed in vitro. In some embodiments, antioxidants are used as food-safe preservatives or antimicrobial agents.

[0102] As used herein, "ice-structuring proteins" or "ice-binding proteins" refer to a class of polypeptides produced by animals, plants, fungi, and bacteria. Ice-structuring proteins function as food preservatives. Non-limiting examples include antifreeze proteins and ice-nucleating proteins, which interact with ice and affect the size and structure of ice crystals. Generally, ice-structuring proteins preserve the structure of milk.

[0103] As used herein, "lipase inhibitor" refers to a molecule that specifically binds to and inhibits the activity of lipase. As used herein, "lipolysis" refers to the process of breaking down fats and hydrolyzing other lipids to release fatty acids.

[0104] As used herein, "synthetic human milk," "artificial milk," or "engineered laboratory milk" refers to milk produced by fermentation or from human cell lines.

[0105] As used herein, "preservation" refers to maintaining an original or existing state.

[0106] As used herein, the terms "ANGPTL3" and "angiopoietin-like 3" refer to ANGPTL3 proteins, peptides, or polypeptides. Non-limiting examples include, for example, GenBank Accession No. NM_014495.4, which is incorporated by reference in its entirety. Furthermore, the term "ANGPTL3" may also refer to nucleic acid sequences encoding ANGPTL3 proteins, peptides, or polypeptides. Examples of ANGPTL3 transcripts include, for example, GenBank Accession No. NM_014495.4, which is incorporated by reference in its entirety. The term "ANGPTL3" may also include other sequences encoding ANGPTL3, such as ANGPTL3 isoforms, mutant ANGPTL3 genes, splice variants of the ANGPTL3 gene, and polymorphisms of the ANGPTL3 gene. The term "ANGPTL3" may also refer to polypeptide gene products encoded by ANGPTL3 genes / transcripts, such as nucleic acid sequences encoding the ANGPTL3 proteins, peptides, or polypeptides disclosed herein.

[0107] As used herein, the terms "ANGPTL8," "angiopoietin-like 8," and "lipasin" refer to ANGPTL8 proteins, peptides, or polypeptides. Non-limiting examples include GenBank Accession No. NM_018687.7, which is incorporated by reference in its entirety. Furthermore, the term "ANGPTL8" may also refer to nucleic acid sequences encoding ANGPTL8 proteins, peptides, or polypeptides. Examples of ANGPTL8 transcripts include GenBank Accession No. NM_018687.7, which is incorporated by reference in its entirety. The term "ANGPTL8" may also include other sequences encoding ANGPTL8, such as ANGPTL8 isoforms, mutant ANGPTL8 genes, splice variants of the ANGPTL8 gene, and polymorphisms of the ANGPTL8 gene. The term "ANGPTL8" may also refer to nucleic acid sequences encoding the polypeptide gene products of the ANGPTL8 genes / transcripts disclosed herein. For example, ANGPTL8 proteins, peptides, or polypeptides.

[0108] As used herein, the term "ANGPTL4" or "angiopoietin-like 4" refers to an ANGPTL4 protein, peptide, or polypeptide. Non-limiting examples include, for example, GenBank accession number NM_139314.3, which is incorporated by reference in its entirety. Furthermore, the term "ANGPTL4" may also refer to a nucleic acid sequence encoding an ANGPTL4 protein, peptide, or polypeptide. An example of an ANGPTL4 transcript is GenBank accession number NM_139314.3, which is incorporated by reference in its entirety. The term "ANGPTL4" may also include other sequences encoding ANGPTL4, such as ANGPTL4 isoforms, mutant ANGPTL4 genes, splice variants of the ANGPTL4 gene, and polymorphisms of the ANGPTL4 gene. The term "ANGPTL4" may also refer to a nucleic acid sequence encoding a polypeptide gene product (e.g., an ANGPTL8 protein, peptide, or polypeptide disclosed herein) encoded by an ANGPTL4 gene / transcript.

[0109] As used herein, the terms "milk storage container," "milk collection container," or "storage container" refer to any suitable container for storing human milk. Non-limiting examples include plastic cups, plastic human milk storage bags, or plastic biological collection containers suitable for collecting biological samples or biological fluids.

[0110] (Composition for preserving human milk) In one embodiment, the disclosed method includes a composition / process that a user adds to human milk after expressing it and before storing it to protect it from lipid degradation and oxidation that occur during storage. The active ingredients of the preparation can include a single substance or a mixture of substances (e.g., surfactants, proteins, and / or nanoparticles that function as emulsifiers). Representative surfactants generally recognized as safe include polysorbates and citric acid esters of mono- and diglycerides. Ingredients can also include naturally derived emulsifiers such as saponin-rich kili extract. In addition to emulsifying properties, the preparation(s) can include antioxidants and food-safe preservatives (e.g., ascorbic acid-tocopherol mixtures, EDTA, phospholipids, egg yolk, lambda-carrageenan, and / or antimicrobial agents). The former group prevents rancidity due to oxidation, while the latter prevents microbial fermentation. The preparation can further utilize ice-structure-forming proteins (antifreeze proteins) to maintain the emulsion structure of the milk during storage and repeated freeze / thaw cycles. The formulations may further include known lipoprotein lipase (LPL) inhibitor proteins, including angiopoietin-like proteins (ANGPTL 3, 4, and 8), small molecule lipase inhibitors, and / or milk stabilizing proteins (e.g., lactoperoxidase). Notably, the above examples may be used alone or in combination.

[0111] The present disclosure provides compositions for preserving expressed and stored human milk. Generally, the disclosed compositions include at least one active ingredient that prevents rancidity, extends shelf life, and maintains the nutritional properties of human milk after one or more days of storage.

[0112] In some embodiments, the compositions disclosed herein comprise at least one active ingredient selected from at least one emulsifier, at least one antioxidant, at least one ice-structure-forming protein, at least one lipoprotein lipase (LPL) inhibitor protein, at least one small molecule lipase inhibitor, at least one milk-stabilizing protein, at least one glycosaminoglycan, at least one flavonoid, or a combination thereof. In some embodiments, the one or more active ingredients are selected from an emulsifier, an antioxidant, an ice-structure-forming protein, a lipoprotein lipase (LPL) inhibitor protein, a small molecule lipase inhibitor, a milk-stabilizing protein, a glycosaminoglycan, a flavonoid, or a combination thereof. In some embodiments, the compositions comprise one or more emulsifiers. In some embodiments, the compositions comprise one or more antioxidants. In some embodiments, the compositions comprise one or more ice-structure-forming proteins. In some embodiments, the compositions comprise one or more lipoprotein lipase (LPL) inhibitor proteins. In some embodiments, the compositions comprise one or more small molecule lipase inhibitors. In some embodiments, the compositions comprise one or more milk-stabilizing proteins. In some embodiments, the composition comprises one or more glycosaminoglycans. In some embodiments, the composition comprises one or more flavonoids. In some embodiments, the composition comprises one or more, two or more, three or more, four or more, five or more, six or more, seven or more, or eight or more active ingredients. In some embodiments, the composition comprises one or more active ingredients disclosed in Tables 1-12. In some embodiments, the composition comprises at least one active ingredient. In some embodiments, the composition comprises one or more active ingredients. In some embodiments, the composition comprises one or more, two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, or ten or more active ingredients.

[0113] In some embodiments, the compositions disclosed herein preserve human milk containing pectin, vitamin C, and vitamin E. Vitamin C is referred to as ascorbic acid, and vitamin E is referred to as tocopherol. In some embodiments, the vitamin is synthetic vitamin E or natural vitamin E. In some embodiments, vitamin E is synthetic vitamin E. In some embodiments, the vitamin is natural vitamin E. In some embodiments, the compositions disclosed herein can include a combination of synthetic vitamin E and natural vitamin E. In some embodiments, the ascorbic acid is an ascorbic acid derivative. In some embodiments, the tocopherol is a tocopherol derivative. In some embodiments, vitamin C and vitamin E are a vitamin C-vitamin E mixture. In some embodiments, pectin alone reduces or inhibits lipase activity but does not maintain antioxidant activity. In some embodiments, vitamin C alone does not reduce or inhibit lipase activity but maintains antioxidant activity. In some embodiments, vitamin E alone does not reduce or inhibit lipase activity but maintains antioxidant activity. In some embodiments, the combination of vitamin C and vitamin E does not reduce or inhibit lipase activity but maintains antioxidant activity. In some embodiments, pectin, vitamin C, and vitamins act synergistically to reduce or inhibit lipase activity and maintain antioxidant activity. In some embodiments, the composition further comprises lecithin.

[0114] In some embodiments, the composition includes at least one emulsifier selected from surfactants, proteins, and / or nanoparticles that function as emulsifiers. Surfactants are typically detergents. Nonionic surfactants are used as excipients in infant medicines. In some embodiments, the composition includes at least one surfactant. In some embodiments, the at least one surfactant is a polysorbate, a citric acid ester of a monoglyceride or diglyceride, and / or a naturally occurring emulsifier. In some embodiments, the at least one surfactant is a nonionic surfactant. In some embodiments, the at least one nonionic surfactant is selected from Tween™ 20, Tween™ 40, Tween™ 60, or Tween™ 80. In some embodiments, the nonionic surfactant is Tween™ 20. In some embodiments, the nonionic surfactant is Tween™ 40. In some embodiments, the nonionic surfactant is Tween™ 60. In some embodiments, the non-ionic surfactant is Tween™ 80.

[0115] In some embodiments, the composition comprises at least one naturally occurring emulsifier. In some embodiments, the at least one naturally occurring emulsifier is lecithin and / or saponin-rich kilia extract. In some embodiments, the lecithin is derived from sunflower or soybean.

[0116] In some embodiments, the emulsifier is pectin. In some embodiments, the composition comprises at least one pectin. In some embodiments, the composition comprises one or more pectins. Generally, pectins interact with the emulsifying substrate and inhibit lipase adsorption to the surface of the substrate emulsion. In some embodiments, the pectin is poly-D-galacturonic acid methyl ester. In some embodiments, the pectin is apple pectin, citrus pectin, beet pectin, okra pectin, or kiwifruit pectin. In some embodiments, the pectin is selected from the group consisting of apple pectin, citrus pectin, beet pectin, okra pectin, and kiwifruit pectin. In some embodiments, the pectin is apple pectin. In some embodiments, the pectin is citrus pectin. In some embodiments, the pectin is beet pectin. In some embodiments, the pectin is okra pectin. In some embodiments, the pectin is kiwifruit pectin. In some embodiments, the pectin is low methoxy pectin, low methoxy amidated pectin, or high methoxy pectin. In some embodiments, the pectin is a low methoxy pectin. In some embodiments, the pectin is a low methoxy amidated pectin. In some embodiments, the pectin is a high methoxy pectin. In some embodiments, the pectin is a pectin subunit. In some embodiments, the pectin subunit is selected from galacturonic acid, digalacturonic acid, or trigalacturonic acid. In some embodiments, the pectin subunit is selected from the group consisting of galacturonic acid, digalacturonic acid, and trigalacturonic acid. In some embodiments, the pectin is selected from GENU® Pectin Beta, GENU® Pectin LM-106 AS-YA, GENU® Pectin YM-100-L, Pacific RSND pectin, Pacific LM-104 pectin, or Pacific LM-12 pectin. In some embodiments, the pectin is Pacific LM-12 pectin.In some embodiments, the Pacific LM-12 pectin is a citrus pectin.

[0117] In some embodiments, the amount of pectin in the composition may range from about 0.03 mg / ml to about 20 mg / ml.In some embodiments, the amount of pectin in the composition is from about 0.03 mg / ml to about 1 mg / ml, from about 0.03 mg / ml to about 2 mg / ml, from about 0.03 mg / ml to about 3 mg / ml, from about 1 mg / ml to about 2 mg / ml, from about 1 mg / ml to about 3 mg / ml, from about 2 mg / ml to about 3 mg / ml, from about 2 mg / ml to about 4 mg / ml, from about 2 mg / ml to about 5 mg / ml, from about 3 mg / ml to about 4 mg / ml, from about 3 mg / ml to about 5 mg / ml, from about 3 mg / ml to about 6 mg / ml, 4 mg / ml to about 5 mg / ml, 4 mg / ml to about 6 mg / ml, or from about 4 mg / ml to about 6 mg / ml. Approximately 7 mg / ml, approximately 5 mg / ml to approximately 6 mg / ml, approximately 5 mg / ml to approximately 7 mg / ml, approximately 5 mg / ml to approximately 8 mg / ml, 6 mg / ml to approximately 7 mg / ml, approximately 6 mg / ml to approximately 8 mg / ml, approximately 6 mg / ml to approximately 9 mg / ml, approximately 7 mg / ml to approximately 8 mg / ml, approximately 7 mg / ml ml~9mg / ml, 7mg / ml~10mg / ml, 8mg / ml~9mg / ml, 8mg / ml~10mg / ml, 8mg / ml~11mg / ml, 9mg / ml~10mg / ml, 9mg / ml~11mg / ml, 9mg / ml~12mg / ml, about 10mg / ml to about 11mg / ml, about 10mg / ml to about 12mg / ml, about 10mg / ml to about 13mg / ml, about 11mg / ml to about 12mg / ml, about 11mg / ml to about 13mg / ml, about 11mg / ml to about 14mg / ml, about 12mg / ml to about 13 mg / ml, approximately 12 mg / ml to approximately 14 mg / ml, approximately 12 mg / ml to approximately 15 mg / ml, approximately 13 mg / ml to approximately 14 mg / ml, approximately 13 mg / ml to approximately 15 mg / ml, approximately 13 mg / ml to approximately 16 mg / ml, approximately 14 mg / ml to approximately 15 mg / ml, approximately 14 mg / ml to approximately 1 The concentration may be 6 mg / ml, about 14 mg / ml to about 17 mg / ml, about 15 mg / ml to about 16 mg / ml, about 15 mg / ml to about 17 mg / ml, about 15 mg / ml to about 18 mg / ml, 16 mg / ml to about 17 mg / ml, about 16 mg / ml to about 18 mg / ml, 16 mg / ml to about 19 mg / ml, about 17 mg / ml to about 18 mg / ml, about 17 mg / ml to about 19 mg / ml, about 17 mg / ml to about 20 mg / ml, about 18 mg / ml to about 19 mg / ml, about 18 mg / ml to about 20 mg / ml, or about 19 mg / ml to about 20 mg / ml.In some embodiments, the amount of pectin in the composition may range from about 0.034 mg / ml to about 9 mg / ml.

[0118] In some embodiments, the amount of pectin in the composition may be at least 0.03 mg / ml, at least 1 mg / ml, at least 2 mg / ml, at least 3 mg / ml, at least 4 mg / ml, at least 5 mg / ml, at least 6 mg / ml, at least 7 mg / ml, at least 8 mg / ml, at least 9 mg / ml, at least 10 mg / ml, at least 11 mg / ml, at least 12 mg / ml, at least 13 mg / ml, at least 14 mg / ml, at least 15 mg / ml, at least 16 mg / ml, at least 17 mg / ml, at least 18 mg / ml, at least 19 mg / ml, or at least 20 mg / ml. In some embodiments, the amount of pectin in the composition may be about 0.03 mg / ml, about 1 mg / ml, about 2 mg / ml, about 3 mg / ml, about 4 mg / ml, about 5 mg / ml, about 6 mg / ml, about 7 mg / ml, about 8 mg / ml, about 9 mg / ml, about 10 mg / ml, about 11 mg / ml, about 12 mg / ml, about 13 mg / ml, about 14 mg / ml, about 15 mg / ml, about 16 mg / ml, about 17 mg / ml, about 18 mg / ml, about 19 mg / ml, or about 20 mg / ml.

[0119] In some embodiments, the amount of pectin is 20 mg / ml. In some embodiments, the amount of pectin is 0.034 mg / ml. In some embodiments, the amount of pectin is 5 mg / ml. In some embodiments, the amount of pectin is 9 mg / ml.

[0120] In some embodiments, the amount of pectin in the composition may be in the range of about 0.034 mg to about 9 mg, or about 0.03 mg to about 0.1 mg, about 0.03 mg to about 0.3 mg, about 0.03 mg to about 0.9 mg, about 0.1 mg to about 0.3 mg, about 0.1 mg to about 0.9 mg, about 0.1 mg to about 2.7 mg, about 0.3 mg to about 0.9 mg, about 0.3 mg to about 2.7 mg, about 0.9 mg to about 9 mg, or about 2.7 mg to about 9 mg.

[0121] In some embodiments, the amount of pectin in the composition may be in the range of about 5 mg to about 75 mg. In some embodiments, the amount of pectin in the composition may be about 5 mg to about 10 mg, about 5 mg to about 20 mg, about 5 mg to about 30 mg, about 10 mg to about 20 mg, about 10 mg to about 30 mg, about 10 mg to about 40 mg, about 20 mg to about 30 mg, about 20 mg to about 40 mg, about 20 mg to about 50 mg, about 30 mg to about 40 mg, about 30 mg to about 50 mg, about 30 mg to about 60 mg, about 40 mg to about 50 mg, about 40 mg to about 60 mg, about 40 mg to about 70 mg, about 50 mg to about 60 mg, about 50 mg to about 70 mg, about 50 mg to about 75 mg, about 60 mg to about 70 mg, or about 60 mg to about 75 mg.

[0122] In some embodiments, the amount of pectin in the composition may range from about 5 mg to about 1332 mg. In some embodiments, the amount of pectin in the composition is from about 5 mg to about 100 mg, from about 5 mg to about 200 mg, from about 5 mg to about 3000 mg, from about 100 mg to about 200 mg, from about 100 mg to about 300 mg, from about 100 mg to about 400 mg, from about 200 mg to about 300 mg, from about 200 mg to about 400 mg, from about 200 mg to about 500 mg, from about 300 mg to about 400 mg, from about 300 mg to about 500 mg, from about 300 mg to about 600 mg, from about 400 mg to about 500 mg, from about 400 mg to about 600 mg, from about 400 mg to about 700 mg, from about 500 mg to about 600 mg, from about 500 mg to about 700 mg, from about 500 mg to about 800 mg, from about 600 mg to about 700 mg g, about 600 mg to about 800 mg, about 600 mg to about 900 mg, about 700 mg to about 800 mg, about 700 mg to about 900 mg, about 700 mg to about 1000 mg, about 800 mg to about 900 mg, about 800 mg to about 1000 mg, about 800 mg to about 1100 mg, about 900 mg to about 1000 mg, about 900 mg to about 1100 mg, about 900 mg to about 1200 mg, about 1000 mg to about 1100 mg, about 1000 mg to about 1200 mg, about 1000 mg to about 1300 mg, about 1100 mg to about 1200 mg, about 1100 mg to about 1200 mg, about 1100 mg to about 1300 mg, about 1200 mg to about 1300 mg, or about 1200 mg to about 1332 mg.

[0123] In some embodiments, the amount of pectin in the composition may be in the range of about 34 mg to about 9000 mg, about 34 mg to about 100 mg, about 34 mg to about 300 mg, about 34 mg to about 900 mg, about 100 mg to about 300 mg, about 100 mg to about 900 mg, about 100 mg to about 2750 mg, about 300 mg to about 900 mg, about 300 mg to about 2750 mg, about 300 mg to about 8200 mg, about 900 mg to about 2750 mg, about 900 mg to about 8200 mg, about 900 mg to about 9000 mg, about 2750 mg to about 8200 mg, about 2750 mg to about 9000 mg, or about 8200 mg to about 9000 mg.

[0124] In some embodiments, the amount of pectin is about 5 mg. In some embodiments, the amount of pectin is 75 mg. In some embodiments, the amount of pectin is 735 mg. In some embodiments, the amount of pectin is about 1332 mg. In some embodiments, the amount of pectin is 9000 mg.

[0125] In some embodiments, the amount of pectin is about 0.003% w / v, about 0.03% w / v, about 0.1% w / v, about 0.2% w / v, about 0.3% w / v, about 0.4% w / v, about 0.5% w / v, about 0.6% w / v, about 0.7% w / v, about 0.8% w / v, 0.9% w / v, or about 1% w / v or more.

[0126] In some embodiments, the composition comprises at least one antioxidant. In some embodiments, the at least one antioxidant is selected from a food-safe preservative or antimicrobial. In some embodiments, the composition comprises one or more antioxidants. In some embodiments, the composition comprises at least two antioxidants. In some embodiments, the antioxidant is selected from vitamin C or a derivative thereof, vitamin E or a derivative thereof, a vitamin C-vitamin E mixture, ethylenediaminetetraacetic acid (EDTA) or a derivative thereof, phospholipids, egg yolk, or lambda-carrageenan. In some embodiments, the composition comprises vitamin C and vitamin E.

[0127] In some embodiments, the amount of vitamin C in the composition as disclosed herein may be in the range of about 0.6 μg / ml to about 350 μg / ml. In some embodiments, the amount of vitamin C is in the range of about 0.6 μg / ml to about 10 μg / ml, about 0.6 μg / ml to about 20 μg / ml, about 0.6 μg / ml to about 30 μg / ml, about 10 μg / ml to about 20 μg / ml, about 10 μg / ml to about 30 μg / ml, about 10 μg / ml to about 40 μg / ml, about 10 μg / ml to about 50 μg / ml, about 20 μg / ml to about 30 μg / ml, about 20 μg / ml to about 40 μg / ml, about 20 μg / ml to about 50 μg / ml, about 30 μg / ml to about 40 μg / ml, about 30 μg / ml to about 5 0μg / ml, approximately 30μg / ml to approximately 60μg / ml, approximately 40μg / ml to approximately 50μg / ml, approximately 40μg / ml to approximately 60μg / ml, approximately 40μg / ml to approximately 70μg / ml, approximately 50μg / ml to approximately 60μg / ml, approximately 50μg / ml to approximately 70μg / ml, approximately 50μg / ml~about 80μg / ml, about 60μg / ml~about 70μg / ml, about 60μg / ml~about 80μg / ml, about 60μg / ml~about 90μg / ml, about 70μg / ml~about 80μg / ml, about 70μg / ml~about 90μg / ml, about 80μg / ml~ Approximately 90μg / ml, approximately 80μg / ml to approximately 100μg / ml, approximately 80μg / ml to approximately 110μg / ml, approximately 90μg / ml to approximately 100μg / ml, approximately 90μg / ml to approximately 110μg / ml, approximately 90μg / ml to approximately 120μg / ml, approximately 100μg / ml to approximately 1 10μg / ml, about 100μg / ml to about 120μg / ml, about 100μg / ml to about 130μg / ml, about 110μg / ml to about 120μg / ml, about 110μg / ml to about 130μg / ml, about 110μg / ml to about 140μg / ml, about 120μg / m l ~ about 130 μg / ml, about 120 μg / ml to about 140 μg / ml, about 120 μg / ml to about 150 μg / ml, about 130 μg / ml to about 140 μg / ml, about 130 μg / ml to about 150 μg / ml, about 130 μg / ml to about 160 μg / ml, about 140 μg / ml~about 150μg / ml, about 140μg / ml~about 160μg / ml, about 140μg / ml~about 170μg / ml, about 150μg / ml~about 160μg / ml, about 150μg / ml~about 170μg / ml, about 150μg / ml~about 180μg / ml,Approximately 160 μg / ml to approximately 170 μg / ml, approximately 160 μg / ml to approximately 180 μg / ml, approximately 160 μg / ml to approximately 190 μg / ml, approximately 170 μg / ml to approximately 180 μg / ml, approximately 170 μg / ml to approximately 190 μg / ml, approximately 180 μg / ml to approximately 190 μg / ml, approximately 180 μg / ml to approximately 200 μg / ml, approximately 180 μg / ml to approximately 210 μg / ml, approximately 190 μg / ml to approximately 210 μg / ml, approximately 190 μg / ml to approximately 220 μg / ml, approximately 200 μg / ml to approximately 210 μg / ml, approximately 200 μg / ml ~approx. 220 μg / ml, approx. 200 μg / ml~approx. 230 μg / ml, approx. 210 μg / ml~approx. 220 μg / ml, approx. 210 μg / ml~approx. 230 μg / ml, approx. 210 μg / ml~approx. 240 μg / ml, approx. 220 μg / ml~approx. 230 μg / ml~approx. 240 μg / ml, approx. 220 μg / ml~approx. 250 μg / ml, approx. 230 μg / ml~approx. 240 μg / ml~approx. 250 μg / ml, approx. 230 μg / ml~approx. 260 μg / ml, approx. 240 μg / ml~approx. 250 μg / ml, approx. 240 μg / ml~approx. 260 μg / ml l, approximately 240 μg / ml to approximately 270 μg / ml, approximately 250 μg / ml to approximately 260 μg / ml, approximately 250 μg / ml to approximately 270 μg / ml, approximately 2250 μg / ml to approximately 80 μg / ml, approximately 260 μg / ml to approximately 270 μg / ml, approximately 260 μg / ml to approximately 280 μg / ml, approximately 260 μg / ml to approximately 290 μg / ml, approximately 270 μg / ml to approximately 280 μg / ml, approximately 270 μg / ml to approximately 290 μg / ml, approximately 270 μg / ml to approximately 300 μg / ml, approximately 280 μg / ml to approximately 290 μg / ml, approximately 280 μg / ml to approximately 300 μg / ml ~approx. 310 μg / ml, approx. 290 μg / ml ~ approx. 300 μg / ml, approx. 290 μg / ml ~ approx. 310 μg / ml, 290 μg / ml ~ approx. 320 μg / ml, approx. 300 μg / ml ~ approx. 310 μg / ml ~ approx. 320 μg / ml, approx. 310 μg / ml ~ approx. 330 μg / ml, approx. 310 μg / ml ~ approx. 340 μg / ml, approx. 320 μg / ml ~ approx. 330 μg / ml, approx. 320 μg / ml ~ approx. 340 μg / mlThe amount of vitamin C in the composition may be from about 330 μg / ml to about 340 μg / ml, from about 330 μg / ml to about 350 μg / ml, or from about 340 μg / ml to about 350 μg / ml. In some embodiments, the amount of vitamin C in the composition may be in the range of from about 676 μg / ml to about 101 μg / ml.

[0128] In some embodiments, the amount of vitamin C in the composition is at least 0.034 μg / ml, at least 2.5 μg / ml, at least 10 μg / ml, at least 20 μg / ml, at least 30 μg / ml, at least 40 μg / ml, at least 50 μg / ml, at least 60 μg / ml, at least 70 μg / ml, at least 80 μg / ml, at least 90 μg / ml, at least 100 μg / ml, at least 110 μg / ml, at least 120 μg / ml, at least 130 μg / ml, at least 140 μg / ml, at least 150 μg / ml, at least 160 μg / ml, at least It may be at least 170 μg / ml, at least 180 μg / ml, at least 190 μg / ml, at least 200 μg / ml, at least 210 μg / ml, at least 220 μg / ml, at least 230 μg / ml, at least 240 μg / ml, at least 250 μg / ml, at least 260 μg / ml, at least 270 μg / ml, at least 280 μg / ml, at least 290 μg / ml, at least 300 μg / ml, at least 310 μg / ml, at least 320 μg / ml, at least 330 μg / ml, at least 340 μg / ml, or at least 350 μg / ml. In some embodiments, the amount of vitamin C in the composition is about 2.5 μg / ml, about 10 μg / ml, about 20 μg / ml, about 30 μg / ml, about 40 μg / ml, about 50 μg / ml, about 60 μg / ml, about 70 μg / ml, about 80 μg / ml, about 90 μg / ml, about 100 μg / ml, about 110 μg / ml, about 120 μg / ml, about 130 μg / ml, about 140 μg / ml, about 150 μg / ml, about 160 μg / ml, about 170 μg / ml, about 180 μg / ml, about 190 μg / ml, about 200 μg / ml, about 210 μg / ml, about 220 μg / ml, about 230 μg / ml, about 240 μg / ml, about 250 μg / ml, about 260 μg / ml, about 270 μg / ml, about 280 μg / ml, about 290 μg / ml, about 300 μg / ml, about 310 μg / ml, about 320 μg / ml, about 330 μg / ml, about 340 μg / ml, about 350 μg / ml, about 360 μg / ml, about 370 μg / ml, about 380 μg / ml, about 390 μg / ml, about 400 μg / ml, about 410 μg / ml, about 420 μg / ml, about 430 μg / ml, about 440 μg / ml, about 450 μg / ml, about 460 μg / ml, about 470 μg / ml, about 480 μg / ml, about 490 μg / ml, about 500 μg / ml, about 180 μg / ml, about 190 μg / ml, about 200 μg / ml, about 210 μg / ml, about 220 μg / ml, about 230 μg / ml, about 240 μg / ml, about 250 μg / ml, about 260 μg / ml, about 270 μg / ml, about 280 μg / ml, about 290 μg / ml, about 300 μg / ml, about 310 μg / ml, about 320 μg / ml, about 330 μg / ml, about 340 μg / ml, or about 350 μg / ml.

[0129] In some embodiments, the amount of vitamin C in the composition may be in the range of about 0.676 μg to about 101 μg. In some embodiments, the amount of vitamin C in the composition may be in the range of about 0.6 μg to about 2.7 μg, about 0.6 μg to about 10.8 μg, about 0.6 μg to about 43.2 μg, about 2.7 μg to about 10.8 μg, about 2.7 μg to about 43.2 μg, about 2.7 μg to about 101 μg, about 10.8 μg to about 43.2 μg, about 10.8 μg to about 101 μg, or about 43.2 μg to about 101 μg.

[0130] In some embodiments, the amount of vitamin C in the composition may be in the range of about 0.1 mg to about 15 mg. In some embodiments, the amount of vitamin C in the composition may be in the range of about 0.1 mg to about 1 mg, about 0.1 mg to about 2 mg, about 0.1 mg to about 3 mg, about 1 mg to about 2 mg, about 1 mg to about 3 mg, about 1 mg to about 4 mg, about 2 mg to about 3 mg, about 2 mg to about 4 mg, about 2 mg to about 5 mg, about 3 mg to about 4 mg, about 3 mg to about 5 mg, about 3 mg to about 6 mg, about 4 mg to about 5 mg, about 4 mg to about 6 mg, 4 mg to about 7 mg, about 5 mg to about 6 mg, about 5 mg to about 7 mg, about 5 mg to about 8 mg, about 6 mg to about 7 mg, about 6 mg to about 8 mg, about 6 mg to about 9 mg, about 7 mg about 8 mg, about 7 mg to about 9 mg, about 7 mg to about 10 mg, about 8 mg to about 9 mg, about 8 mg to about 10 mg, about 8 mg to about 11 mg, about 9 mg to about 10 mg, about 9 mg to about 11 mg, about 9 mg to about 12 mg, about 10 mg to about 11 mg, about 10 mg to about 12 mg, about 10 mg to about 13 mg, about 11 mg to about 12 mg, about 11 mg to about 13 mg, about 11 mg to about 14 mg, about 12 mg to about 13 mg, about 12 mg to about 14 mg, about 12 mg to about 15 mg, about 13 mg to about 14 mg, about 13 mg to about 15 mg, or about 14 mg to about 15 mg.

[0131] In some embodiments, the amount of vitamin C in the composition may range from about 0.676 mg to about 101 mg. In some embodiments, the amount of vitamin C in the composition may be from about 0.6 mg to about 2.7 mg, from about 0.6 mg to about 10.8 mg, from about 0.6 mg to about 43.2 mg, from about 2.7 mg to about 10.8 mg, from about 2.7 mg to about 43.2 mg, from about 2.7 mg to about 101 mg, from about 10.8 mg to about 43.2 mg, from about 10.8 mg to about 101 mg, or from about 43.2 mg to about 101 mg.

[0132] In some embodiments, the amount of vitamin C in the composition is 0.1 mg. In some embodiments, the amount of vitamin C is 0.1014 mg. In some embodiments, the amount of vitamin C in the composition is 15 mg. In some embodiments, the amount of vitamin C in the composition is 101.4 mg.

[0133] In some embodiments, the amount of vitamin E in the composition as disclosed herein may range from about 0.01 mg / ml to about 150 mg / ml. In some embodiments, the amount of vitamin E ranges from about 0.01 mg / ml to about 10 mg / ml, from about 0.01 mg / ml to about 20 mg / ml, from about 0.01 mg / ml to about 30 mg / ml, from about 10 mg / ml to about 20 μg / ml, from about 10 mg / ml to about 30 mg / ml, from about 10 mg / ml to about 40 mg / ml, from about 20 mg / ml to about 30 μg / ml, from about 20 μg / ml to about 40 μg / ml, from about 20 μg / ml to about 50 μg / ml, or from about 30 μg / ml to about 40 μg / ml. μg / ml, approximately 30μg / ml to approximately 50μg / ml, approximately 30μg / ml to approximately 60μg / ml, approximately 40μg / ml to approximately 50μg / ml, approximately 40μg / ml to approximately 60μg / ml, approximately 40μg / ml to approximately 70μg / ml, approximately 50μ g / ml~about 60μg / ml, about 50μg / ml~about 70μg / ml, about 50μg / ml~about 80μg / ml, about 60μg / ml~about 70μg / ml, about 60μg / ml~about 80μg / ml, about 60μg / ml~about 90μg / ml ml, about 70μg / ml to about 80μg / ml, about 70μg / ml to about 90μg / ml, about 80μg / ml to about 90μg / ml, about 80μg / ml to about 100μg / ml, about 80μg / ml to about 110μg / ml, about 90μg / ml~about 100μg / ml, about 90μg / ml~about 110μg / ml, about 90μg / ml~about 120μg / ml, about 100μg / ml~about 110μg / ml, about 100μg / ml~about 120μg / ml, about 100μg / ml to about 130 μg / ml, about 110 μg / ml to about 120 μg / ml, about 110 μg / ml to about 130 μg / ml, about 110 μg / ml to about 140 μg / ml, about 120 μg / ml to about 130 μg / ml, about 120 μg / ml to about 140 μg / ml, about 120 μg / ml to about 150 μg / ml, about 130 μg / ml to about 140 μg / ml, about 130 μg / ml to about 150 μg / ml, or about 140 μg / ml to about 150 μg / ml.

[0134] In some embodiments, the amount of vitamin E in the composition may be at least 0.01 μg / ml, at least 1.15 μg / ml, at least 10 μg / ml, at least 20 μg / ml, at least 30 μg / ml, at least 40 μg / ml, at least 50 μg / ml, at least 60 μg / ml, at least 70 μg / ml, at least 80 μg / ml, at least 90 μg / ml, at least 100 μg / ml, at least 110 μg / ml, at least 120 μg / ml, at least 130 μg / ml, at least 140 μg / ml, or at least 150 μg / ml. In some embodiments, the amount of vitamin E in the composition may be about 1.15 μg / ml, about 10 μg / ml, about 20 μg / ml, about 30 μg / ml, about 40 μg / ml, about 50 μg / ml, about 60 μg / ml, about 70 μg / ml, about 80 μg / ml, about 90 μg / ml, about 100 μg / ml, about 110 μg / ml, about 120 μg / ml, about 130 μg / ml, about 140 μg / ml, or about 150 μg / ml.

[0135] In some embodiments, the amount of vitamin E in the composition may range from about 0.0000271 IU to about 0.004 IU. In some embodiments, the amount of vitamin E in the composition may be from about 0.0000271 IU to about 0.0001 IU, from about 0.0000271 IU to about 0.0001 IU, from about 0.0000271 IU to about 0.0001 IU, from about 0.0001 IU to about 0.0004 IU, from about 0.0001 IU to about 0.001 IU, from about 0.0001 IU to about 0.004 IU, from about 0.0004 IU to about 0.001 IU, from about 0.0004 IU to about 0.004 IU, or from about 0.001 IU to about 0.004 IU.

[0136] In some embodiments, the amount of vitamin E in the composition may range from about 0.004 IU to about 0.6 IU. In some embodiments, the amount of vitamin E in the composition may be about 0.004 IU to about 0.1 IU, about 0.004 IU to about 0.2 IU, about 0.004 IU to about 0.3 IU, about 0.1 IU to about 0.2 IU, about 0.1 IU to about 0.3 IU, about 0.1 IU to about 0.4 IU, about 0.2 IU to about 0.3 IU, about 0.2 IU to about 0.4 IU, about 0.2 IU to about 0.5 IU, about 0.3 IU to about 0.4 IU, about 0.3 IU to about 0.5 IU, about 0.3 IU to about 0.6 IU, about 0.4 IU to about 0.5 IU, about 0.4 IU to about 0.6 IU, or about 0.5 IU to about 0.6 IU.

[0137] In some embodiments, the amount of vitamin E in the composition may range from about 0.0271 IU to about 4 IU. In some embodiments, the amount of vitamin E in the composition may be from about 0.0271 IU to about 0.1 IU, from about 0.0271 IU to about 0.4 IU, from about 0.0271 IU to about 1.7 IU, from about 0.1 IU to about 0.4 IU, from about 0.1 IU to about 1.7 IU, from about 0.1 IU to about 4 IU, from about 0.4 IU to about 1.7 IU, from about 0.4 IU to about 4 IU, or from about 1.7 IU to about 4 IU.

[0138] In some embodiments, the amount of vitamin E in the composition is about 0.004 IU. In some embodiments, the amount of vitamin E is about 0.00406 IU. In some embodiments, the amount of vitamin E is about 0.6 IU. In some embodiments, the amount of vitamin E is about 4 IU.

[0139] In some embodiments, the amount of natural vitamin E in the composition may be in the range of about 0.01 μg to about 2.68 μg, or about 0.01 μg to about 0.04 μg, about 0.01 μg to about 0.16 μg, about 0.01 μg to about 0.64 μg, about 0.04 μg to about 0.16 μg, about 0.04 μg to about 0.64 μg, about 0.04 μg to about 2.68 μg, about 0.16 μg to about 0.64 μg, about 0.16 μg to about 2.68 μg, or about 0.64 μg to about 2.68 μg.

[0140] In some embodiments, the amount of natural vitamin E in the composition may be in the range of about 0.00268 mg to about 0.402 mg. In some embodiments, the amount of vitamin E in the composition may be about 0.002 mg or more, about 0.006 mg or more, about 0.018 mg or more, about 0.054 mg or more, about 0.162 mg or more, or about 0.4 mg or more, or more. In some embodiments, the amount of natural vitamin E is about 0.00268 mg. In some embodiments, the amount of natural vitamin E is about 0.402 mg.

[0141] In some embodiments, the amount of natural vitamin E in the composition may be in the range of about 0.01 mg to about 2.68 mg. In some embodiments, the amount of natural vitamin E in the composition may be about 0.01 mg to about 0.04 mg, about 0.01 mg to about 0.16 mg, about 0.01 mg to about 0.64 mg, about 0.04 mg to about 0.16 mg, about 0.04 mg to about 0.64 mg, about 0.04 mg to about 2.68 mg, about 0.16 mg to about 0.64 mg, about 0.16 mg to about 2.68 mg, or about 0.64 mg to about 2.68 mg.

[0142] In some embodiments, the amount of natural vitamin E in the composition is about 0.00406 mg or about 0.402 mg. In some embodiments, the amount of natural vitamin E in the composition is about 2.68 mg.

[0143] In some embodiments, the amount of synthetic vitamin E in the composition may be in the range of about 0.0122 μg to about 1.8 μg, or about 0.0122 μg to about 0.04 μg, about 0.0122 μg to about 0.16 μg, about 0.0122 μg to about 0.64 μg, about 0.04 μg to about 0.16 μg, about 0.04 μg to about 0.64 μg, about 0.04 μg to about 1.8 μg, about 0.16 μg to about 0.64 μg, about 0.16 μg to about 1.8 μg, or about 0.64 μg to about 1.8 μg.

[0144] In some embodiments, the amount of synthetic vitamin E in the composition may be in the range of about 0.0122 mg to about 1.8 mg. In some embodiments, the amount of synthetic vitamin E in the composition may be about 0.0122 mg to about 0.04 mg, about 0.0122 mg to about 0.16 mg, about 0.0122 mg to about 0.64 mg, about 0.04 mg to about 0.16 mg, about 0.04 mg to about 0.64 mg, about 0.04 mg to about 1.8 mg, about 0.16 mg to about 0.64 mg, about 0.16 mg to about 1.8 mg, or about 0.64 mg to about 1.8 mg.

[0145] In some embodiments, the amount of synthetic vitamin E in the composition may be in the range of about 0.0018 mg to about 0.27 mg. In some embodiments, the amount of vitamin E in the composition is about 0.001 mg or more, about 0.003 mg or more, about 0.009 mg or more, about 0.027 mg or more, about 0.081 mg or more, or 0.2 mg or more. In some embodiments, the amount of natural vitamin E is about 0.0018 mg. In some embodiments, the amount of synthetic vitamin E is about 0.27 mg.

[0146] In some embodiments, the composition comprises at least one ice-structure-forming protein (i.e., ice-binding protein). In some embodiments, the composition comprises at least one cryopreservative. In some embodiments, the cryopreservative is trehalose.

[0147] Generally, lipolysis is the process by which lipids or fats are broken down into free fatty acids by lipases. Excessive lipase activity can lead to the production of excess fatty acids, which can promote rancidity of milk during storage. At least two types of lipases are present in human milk: bile acid-dependent lipase and lipoprotein lipase (LPL). Lipase inhibitors can inhibit the function of lipases. In some embodiments, the composition comprises at least one lipase inhibitor. In some embodiments, the composition comprises at least one lipoprotein lipase (LPL) inhibitor protein. In some embodiments, the composition comprises one or more LPL inhibitor proteins. In some embodiments, the LPL inhibitor protein is ANGPTL3, ANGPTL4, and / or ANGPTL8. In some embodiments, the LPL inhibitor protein is selected from ANGPTL3, ANGPTL4, or ANGPTL8. In some embodiments, the LPL inhibitor protein is selected from ANGPTL3, ANGPTL4, and ANGPTL8. In some embodiments, the LPL inhibitor protein is ANGPTL3. In some embodiments, the LPL inhibitory protein is ANGPTL4. In some embodiments, the LPL inhibitory protein is ANGPTL8. In some embodiments, the composition may comprise one LPL inhibitory protein. In some embodiments, the one LPL inhibitory protein is ANGPTL3, ANGPTL4, or ANGPTL8. In some embodiments, the composition may comprise two LPL inhibitory proteins. In some embodiments, the two LPL inhibitory proteins are selected from ANGPTL3, ANGPTL4, or ANGPTL8. In some embodiments, the composition may comprise three LPL inhibitory proteins. In some embodiments, the three LPL inhibitory proteins are ANGPTL3, ANGPTL4, and ANGPTL8. In some embodiments, the composition comprises a small molecule lipase inhibitor. In some embodiments, the lipase inhibitor is a lipase-specific antibody. In some embodiments, the lipase inhibitor is synthetic.

[0148] In some embodiments, the composition does not contain one or more active ingredients that bind to lipase. In some embodiments, the composition does not contain one or more active ingredients that are antibodies or proteins that bind to lipase or directly interact with lipase. In some embodiments, the composition does not contain one or more active ingredients that are antibodies or proteins that bind to LPL. In some embodiments, the one or more active ingredients are not lipase inhibitors selected from GSK264220A, Orlistat, RHC 80267, and Xen 445.

[0149] In some embodiments, the composition includes at least one dairy stabilizer. Non-limiting examples include, but are not limited to, gums, fibers, polysaccharides including starch, or proteins including whey and gelatin. In some embodiments, the dairy stabilizer can have thickening or gelling properties. Generally, dairy stabilizers bind water and reduce the interfacial tension between the oil (fat droplets) and aqueous phases, thereby keeping dairy products and dairy compositions in solution and preventing an unpleasant appearance or mouthfeel. In some embodiments, the dairy stabilizer may be an antibacterial agent. In some embodiments, the composition includes a dairy stabilizing protein. In some embodiments, the dairy stabilizing protein is lactoperoxidase.

[0150] In some embodiments, the composition comprises at least one glycosaminoglycan (GAG). GAGs generally play a role in cell signaling processes and are used in human supplements. Non-limiting examples include cell growth regulation, proliferation, promotion of cell adhesion, anticoagulation, and wound repair. In some embodiments, the at least one glycosaminoglycan is selected from glucosamine sulfate, chondroitin sulfate, hyaluronic acid, heparan sulfate, or fucoidan. In some embodiments, the glycosaminoglycan is chondroitin sulfate. In some embodiments, the glycosaminoglycan is fucoidan.

[0151] In some embodiments, the composition comprises at least one flavonoid.Flavonoids (also known as vitamin P) generally come from plants with diverse phenolic structures.In some embodiments, the at least one flavonoid is selected from ginkgo, isoginkgo, myricetin, luteolin, or epigallocatechin gallate.

[0152] In some embodiments, the composition comprises one or more active ingredients that are not naturally occurring in mammalian milk. In some embodiments, the composition comprises one or more active ingredients that are not naturally occurring in human milk. In some embodiments, one active ingredient does not naturally occur in human milk.

[0153] In some embodiments, the compositions disclosed herein include one or more of disintegrants, adsorbents, colorants, flavorings, sweeteners, or dispersants. Non-limiting examples of disintegrants include starch, agar, methylcellulose, bentonite, xanthan gum, alginic acid or its sodium salt, or effervescent mixtures. Non-limiting examples of dispersants include Labrasol, HPMC, DOSS, Caproyl 909, Labrafac, Labraphil, Peceol, Transcutol, Capmul MCM, Capmul PG-12, Captex 355, or Gelucire.

[0154] In some embodiments, the compositions disclosed herein comprise a binder, non-limiting examples of which include magnesium aluminum silicate, starch paste, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose, magnesium carbonate, natural sugars such as glucose or beta-lactose, corn syrup, natural and synthetic gums such as acacia, tragacanth, or sodium alginate, waxes, and polyvinylpyrrolidone.

[0155] In some embodiments, the compositions disclosed herein include an agent that enhances the absorption of one or more active ingredients. Non-limiting examples include cyclodextrin, hydroxypropyl cyclodextrin, PEG400, and PEG200.

[0156] In some embodiments, the compositions disclosed herein are prepared in the form of a concentrated liquid, a tablet, a powder, or a single-use sachet. In some embodiments, the compositions are prepared in the form of a tablet. In some embodiments, the tablet disintegrates in a solution. In some embodiments, the prepared powder is encapsulated.

[0157] Tablets are generally formed by, for example, powdered compounds with or without being moistened with an inert liquid component, using a suitable tablet machine. Tablets can be optionally coated or scored to prepare them for sustained or controlled release. Tablets can also be optionally coated with a coating such as a thin film or sugar coating. Tablet and capsule manufacturing processes, equipment, and contract manufacturers are well known to those skilled in the art.

[0158] In some embodiments, the composition comprises a pharmaceutically acceptable carrier, excipient, and / or diluent. Examples of suitable carriers, excipients, and diluents include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, microcrystalline phosphocellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, minerals, and the like. In some embodiments, the composition or active ingredient is present in water or other pharmaceutically acceptable water-soluble carrier in which the complex has good solubility, with or without other pharmaceutically acceptable excipients or preservatives as needed.

[0159] In some embodiments, the compositions disclosed herein reduce lipase activity and maintain antioxidant capacity in human milk. In some embodiments, the compositions prevent rancidity in human milk. In some embodiments, the compositions extend the shelf life of human milk. In some embodiments, the compositions maintain the nutritional properties of human milk. In some embodiments, the compositions maintain the nutritional properties of human milk during storage. In some embodiments, the compositions prevent rancidity, extend the shelf life, maintain the nutritional properties, and / or maintain the nutritional properties during storage of human milk. In some embodiments, the compositions disclosed herein are provided for use in preventing rancidity, extending the shelf life, and / or maintaining the nutritional properties during storage of human milk.

[0160] The compositions disclosed herein can be used to preserve mammalian milk. In some embodiments, the mammal is a human.

[0161] (How to store human milk) The present disclosure provides a method of preserving human milk, the method comprising contacting human milk with a composition disclosed herein.

[0162] The present disclosure provides a method for preserving human milk, the method comprising contacting human milk with a composition described herein and storing the human milk. The present disclosure further provides a method for preventing rancidity in human milk, extending the shelf life of human milk, and / or maintaining the nutritional properties of human milk during storage. In some embodiments, the method comprises contacting human milk with a composition described herein. In some embodiments, the method is intended to prevent rancidity in human milk. In some embodiments, the method is intended to extend the shelf life of human milk. In some embodiments, the method is intended to maintain the nutritional properties of human milk. In some embodiments, the method is intended to maintain the nutritional properties of human milk during storage. In some embodiments, the composition comprises at least one active ingredient selected from at least one emulsifier, at least one antioxidant, at least one ice-structure-forming protein, at least one lipoprotein lipase (LPL) inhibitor protein, at least one small molecule lipase inhibitor, at least one milk-stabilizing protein, at least one glycosaminoglycan, at least one flavonoid, or a combination thereof. In some embodiments, the composition comprises pectin, vitamin C, and vitamin E, as disclosed herein. In some embodiments, the composition is formulated as a tablet. In some embodiments, the composition comprises a binder.

[0163] In some embodiments, methods disclosed herein for preserving human milk include: (a) contacting the human milk with a composition comprising: (i) from about 0.034 mg / ml to about 9 mg / ml of pectin; (ii) from about 0.676 μg / ml to about 101 μg / ml of vitamin C; and (iii) from about 0.0182 μg / ml to about 2.68 μg / ml of natural vitamin E or from about 0.0122 μg / ml to about 1.8 μg / ml of synthetic vitamin E; and (b) storing the human milk.

[0164] In some embodiments, the methods disclosed herein reduce lipase activity in human milk and preserve antioxidant capacity.

[0165] In some embodiments, storing comprises freezing the human milk at about -20°C. In some embodiments, storing occurs at about -20°C. In some embodiments, storing comprises freezing the human milk at a temperature of about 0°C, about -2°C, about -4°C, about -8°C, about -10°C, about -12°C, about -14°C, about -16°C, about -18°C, or about -20°C or below. In some embodiments, storing comprises freezing the human milk at a temperature of at least about 0°C, at least about -2°C, at least about -4°C, at least about -8°C, at least about -10°C, at least about -12°C, at least about -14°C, at least about -16°C, at least about -18°C, or at least about -20°C or below. In some embodiments, storing comprises freezing the human milk below about -20°C. In some embodiments, storing comprises freezing the human milk at a temperature of at least about -30°C, at least about -40°C, at least about -50°C, at least about -60°C, at least about -70°C, or at least about -80°C. In some embodiments, storing comprises freezing the human milk at a temperature below about -80°C. In some embodiments, freezing comprises deep freezing. In some embodiments, storing comprises freezing in liquid nitrogen.

[0166] In some embodiments, storage occurs at about 4° C. In some embodiments, storage occurs at about 2° C., about 4° C., about 6° C., about 8° C., about 10° C., about 12° C., about 14° C., or about 16° C. or below. In some embodiments, storage occurs at a temperature of at least about 2° C., at least about 4° C., at least about 6° C., at least about 8° C., at least about 10° C., at least about 12° C., at least about 14° C., or at least about 16° C. or below.

[0167] In some embodiments, storage occurs at room temperature.

[0168] In some embodiments, the storage period is within the range of about 1 day to about 5 years. In some embodiments, the storage period is within the range of about 1 day to about 2 days, about 1 day to about 3 days, about 1 day to about 4 days, about 2 days to about 3 days, about 2 days to about 4 days, about 2 days to about 5 days, about 3 days to about 4 days, about 3 days to about 5 days, about 3 days to about 6 days, about 4 days to about 5 days, about 4 days to about 6 days, about 4 days to about 7 days, about 5 days to about 6 days, about 5 days to about 7 days, about 6 days to about 7 days, about 1 week to about 2 weeks, about 1 week to about 2 weeks, about 1 week to about 3 weeks, about 2 weeks to about 3 weeks, about 2 weeks to 4 weeks, about 3 weeks to 4 weeks, about 1 month to 1.5 months, about 1 month to 2 months, about 1.5 months to 2 months, 2 months to 4 months, about 2 months to 6 months, about 2 months to 8 months, about 4 months to 6 months, about 4 months to 8 months, 4 months to 10 months, about 6 months to 8 months, about 6 months to 10 months, about 6 months to 12 months, about 8 months to 10 months, about 8 months to 12 months, about 8 months to 14 months, about 1 0 months to approximately 12 months, approximately 10 months to approximately 14 months, approximately 10 months to approximately 16 months, approximately 12 months to approximately 14 months, approximately 12 months to approximately 16 months, approximately 12 months to approximately 18 months, approximately 14 months to approximately 16 months, approximately 14 months to approximately 18 months, approximately 14 months to approximately 20 months, approximately 16 months to approximately 18 months, approximately 16 months to approximately 20 months, approximately 16 months to approximately 22 months, approximately 18 months to approximately 20 months, approximately 18 months to approximately 22 months, approximately 18 months to approximately 24 months, approximately 20 months to about 22 months, about 20 months to about 24 months, about 22 months to about 24 months, about 2 years to about 2.5 years, about 2 years to 3 years, about 2 years to 3.5 years, about 2.5 years to about 3 years, about 2.5 years to 3.5 years, about 2.5 years to 4 years, about 3 years to about 3.5 years, about 3 years to about 4 years, 3 to about 4.5 years, 3.5 years to about 4 years, 3.5 years to about 4.5 years, 3.5 years to about 5 years, 4 to about 4.5 years, 4 to about 5 years, or 4.5 years to about 5 years or more.

[0169] In some embodiments, as disclosed herein, the amount of human milk is in the range of about 1 ml to about 150 ml. In some embodiments, the amount of human milk is in the range of about 1 ml to about 10 ml, about 1 ml to about 20 ml, about 1 ml to about 30 ml, about 10 ml to about 20 ml, about 10 ml to about 30 ml, about 10 ml to about 40 ml, about 20 ml to about 30 ml, about 20 ml to about 40 ml, about 20 ml to about 50 ml, about 30 ml to about 40 ml, about 30 ml to about 50 ml, about 30 ml to about 60 ml, about 40 ml to about 50 ml, about 40 ml to about 60 ml, about 40 ml to about 70 ml, about 50 ml to about 60 ml, about 50 ml to about 70 ml, about 50 ml to about 80 ml, about 60 ml to about 70 ml, about 60 ml to about 80 ml, about 60 ml to about 90 ml, about 70 ml ml ~ about 80ml, about 70ml - about 90ml, about 80ml - about 90ml, about 80ml - about 100ml, about 80ml - about 110ml, about 90ml - about 100ml, about 90ml - about 110ml, about 90ml - about 120ml, about 100ml - about 110ml, about 100ml - about 120ml, about 100ml - about 13 0ml, about 110ml to about 120ml, about 110ml to about 130ml, about 110ml to about 140ml, about 120ml to about 130ml, about 120ml to about 140ml, about 120ml to about 150ml, about 130ml to about 140ml, about 130ml to about 150ml, or about 140ml to about 150ml.

[0170] In some embodiments, as disclosed herein, the amount of human milk is in the range of about 1 ml to about 1000 ml. In some embodiments, the amount of human milk is in the range of about 1 ml to about 100 ml, about 1 ml to about 200 ml, about 1 ml to about 300 ml, about 100 ml to about 200 ml, about 100 ml to about 300 ml, about 100 ml to about 400 ml, about 200 ml to about 300 ml, about 200 ml to about 400 ml, about 2000 ml to about 50 ml, about 300 ml to about 400 ml, about 300 ml to about 500 ml, about 300 ml to about 600 ml, about 400 ml to about 500 ml. ml, about 400 ml to about 600 ml, about 400 ml to about 700 ml, about 500 ml to about 600 ml, about 500 ml to about 700 ml, about 500 ml to about 80 ml, about 600 ml to about 700 ml, about 600 ml to about 800 ml, about 600 ml to about 900 ml, about 700 ml to about 800 ml, about 700 ml to about 900 ml, about 800 ml to about 900 ml, about 800 ml to about 1000 ml, or about 900 ml to about 1000 ml.

[0171] In some embodiments, the amount of human milk is about 1 ml. In some embodiments, the amount of human milk is about 147.93 ml. In some embodiments, the amount of milk is about 5 ounces.

[0172] In some embodiments, the composition is contacted with human milk before storage. In some embodiments, the composition is contacted with human milk during storage. In some embodiments, the composition is contacted with human milk and the milk is immediately stored. In some embodiments, the human milk is contacted with a composition disclosed herein and then stored for at least 1 day, at least 2 days, at least 3 days, at least 4 days, at least 5 days, at least 6 days, or at least 7 days. In some embodiments, the human milk is contacted with a composition disclosed herein and then stored for about 1 day, about 2 days, about 3 days, about 4 days, about 5 days, about 6 days, or about 7 days or more.

[0173] In some embodiments, the human milk is contacted with a composition disclosed herein immediately after expression. In some embodiments, the human milk is contacted with a composition disclosed herein at least 1 day, at least 2 days, at least 3 days, at least 4 days, at least 5 days, at least 6 days, or at least 7 days after expression. In some embodiments, the human milk is contacted with a composition disclosed herein about 1 day, about 2 days, about 3 days, about 4 days, about 5 days, about 6 days, or about 7 days or more after expression.

[0174] In some embodiments, the human milk is contacted with the composition disclosed herein once. In some embodiments, the human milk is contacted with the composition about once per day during storage. In some embodiments, the human milk is contacted with the composition about once per week during storage. In some embodiments, the human milk is contacted with the composition about once per month during storage. In some embodiments, the human milk is contacted with the composition about once every two months during storage. In some embodiments, the human milk is contacted with the composition about once every six months during storage. In some embodiments, the human milk is contacted with the composition about once per year during storage.

[0175] In some embodiments, the human milk disclosed herein is expressed human milk or synthetic human milk. In some embodiments, the human milk is synthetic and provided as a formula.

[0176] In some embodiments, the human milk is colostrum, transitional milk, mature milk, or a combination thereof. In some embodiments, the human milk is colostrum. In some embodiments, the human milk is transitional milk. In some embodiments, the human milk is mature milk. In some embodiments, the milk is expressed between about 1 day and about 5 years after birth. In some embodiments, the human milk is expressed from about 1 day to about 2 days, about 1 day to about 3 days, about 1 day to about 4 days, about 2 days to about 3 days, about 2 days to about 4 days, about 2 days to about 5 days, about 3 days to about 4 days, about 3 days to about 5 days, about 3 days to about 6 days, about 4 days to about 5 days, about 4 days to about 6 days, about 4 days to about 7 days, about 5 days to about 6 days, about 5 days to about 7 days, about 6 days to about 7 days, about 1 week to about 2 weeks, about 1 week to about 2 weeks, about 1 week to about 3 weeks, about 2 weeks to about 3 weeks, about 2 weeks to about 3 weeks, about 2 weeks to about 7 days, about 3 days to about 6 ... Approximately 4 weeks, approximately 3 weeks to approximately 4 weeks, approximately 1 month to approximately 1.5 months, approximately 1 month to approximately 2 months, approximately 1.5 months to approximately 2 months, 2 months to approximately 4 months, approximately 2 months to approximately 6 months, approximately 2 months to approximately 8 months, approximately 4 months to approximately 6 months, approximately 4 months to approximately 8 months, 4 months to approximately 10 months, approximately 6 months to approximately 8 months, approximately 6 months to approximately 10 months, approximately 6 months to approximately 12 months, approximately 8 months to approximately 10 months, approximately 8 months to approximately 12 months, approximately 8 months to approximately 14 months, approximately 10 months to approximately 12 months , about 10 months to about 14 months, about 10 months to about 16 months, about 12 months to about 14 months, about 12 months to about 16 months, about 12 months to about 18 months, about 14 months to about 16 months, about 14 months to about 18 months, about 14 months to about 20 months, about 16 months to about 18 months, about 16 months to about 20 months, about 16 months to about 22 months, about 18 months to about 20 months, about 18 months to about 22 months, about 18 months to about 24 months, about 20 months to about 22 months, about 20 The milk has been extracted after a period of from about 22 months to about 24 months, from about 22 months to about 24 months, from about 2 years to about 2.5 years, from about 2 years to about 3 years, from about 2 years to about 3.5 years, from about 2.5 years to about 3 years, from about 2.5 years to 3.5 years, from about 2.5 years to 4 years, from about 3 years to about 3.5 years, from about 3 years to about 4 years, from 3 years to about 4.5 years, from 3.5 years to about 4 years, from 3.5 years to about 4.5 years, from 3.5 years to about 5 years, from 4 years to about 4.5 years, from 4 years to about 5 years, or from 4.5 years to about 5 years, or more.

[0177] (Devices for storing or preserving human milk and milk storage containers) Another embodiment includes a coating comprising one or more of the above-mentioned compounds embedded with immobilization chemistry into a milk storage container before pre-storage milk is added.

[0178] Yet another embodiment is a non-dissolving aerating device, such as a filter or capsule, containing one or more of the above-described formulations therein. In this case, the breathable device is added to a container of human milk prior to storage and captures or adsorbs lipolytic enzymes, oxidants, and rancidity-promoting factors. After the human milk is thawed, the unwanted enzymes, oxidants, and rancidity-promoting factors can be removed from the container. Optionally, the breathable device is reusable (FIG. 12A).

[0179] In yet another embodiment, a filter cartridge placed between the milk pump and the milk storage container filters, adsorbs, or detoxifies lipolytic enzymes, oxidants, and rancidity-promoting factors from the milk while the milk is being collected (FIG. 12B).

[0180] The present disclosure provides a device for storing human milk, the device comprising a housing defining an interior volume of a space, the housing having at least one opening configured to allow a substance within the interior volume of the space to exit the housing and contact the human milk or to contact the human milk within the interior volume of the space, the substance within the interior volume of the space comprising a composition disclosed herein. In some embodiments, the substance is a non-dissolving filter or mesh. In some embodiments, the composition disclosed herein coats the substance.

[0181] In some embodiments, the device is configured to be placed within a human milk collection or storage container.

[0182] In some embodiments, the device is configured to have an inlet and an outlet, and the device is configured to be positioned between the milk pump and the milk storage container so that all milk must pass through the inlet and outlet before entering the milk storage container.

[0183] The present disclosure provides a milk storage container comprising the composition disclosed herein. In some embodiments, the composition is fixed to the inner surface of the container. In some embodiments, the composition can be added to the storage container before human milk is added to the storage container. In some embodiments, the composition can be added to the storage container as a formulation in the form of a concentrated liquid, tablet, or powder.

[0184] In some embodiments, the milk storage container is made of plastic. In some embodiments, the milk storage container is a plastic bag. In some embodiments, the milk storage container is a human milk storage bag. In some embodiments, the human milk storage bag is configured to be stored for at least 5 years at a temperature range of about -80°C to about 4°C.

[0185] In some embodiments, the milk storage bag is configured to be stored for about 1 day to about 5 years. In some embodiments, the milk storage bag is configured to be stored for about 1 day to about 2 days, about 1 day to about 3 days, about 1 day to about 4 days, about 2 days to about 3 days, about 2 days to about 4 days, about 2 days to about 5 days, about 3 days to about 4 days, about 3 days to about 5 days, about 3 days to about 6 days, about 4 days to about 5 days, about 4 days to about 6 days, about 4 days to about 7 days, about 5 days to about 6 days, about 5 days to about 7 days, about 6 days to about 7 days, about 1 week to about 2 weeks, about 1 week to about 2 weeks, about 1 week to about 3 weeks, about 2 weeks to about 3 weeks. weeks, about 2 weeks to about 4 weeks, about 3 weeks to about 4 weeks, about 1 month to about 1.5 months, about 1 month to about 2 months, about 1.5 months to about 2 months, 2 months to about 4 months, about 2 months to about 6 months, about 2 months to about 8 months, about 4 months to about 6 months, about 4 months to about 8 months, 4 months to about 10 months, about 6 months to about 8 months, about 6 months to about 10 months, about 6 months to about 12 months, about 8 months to about 10 months, about 8 months to about 12 months, about 8 months to about 14 months, about 10 months to approximately 12 months, approximately 10 months to approximately 14 months, approximately 10 months to approximately 16 months, approximately 12 months to approximately 14 months, approximately 12 months to approximately 16 months, approximately 12 months to approximately 18 months, approximately 14 months to approximately 16 months, approximately 14 months to approximately 18 months, approximately 14 months to approximately 20 months, approximately 16 months to approximately 18 months, approximately 16 months to approximately 20 months, approximately 16 months to approximately 22 months, approximately 18 months to approximately 20 months, approximately 18 months to approximately 22 months, approximately 18 months to approximately 24 months, approximately 20 The storage period may be from about 2 months to about 22 months, from about 20 months to about 24 months, from about 22 months to about 24 months, from about 2 years to about 2.5 years, from about 2 years to about 3 years, from about 2 years to about 3.5 years, from about 2.5 years to about 3 years, from about 2.5 years to 3.5 years, from about 2.5 years to 4 years, from about 3 years to about 3.5 years, from about 3 years to about 4 years, from 3 to 4.5 years, from 3.5 to 4 years, from 3.5 to 4.5 years, from 3.5 to 5 years, from 4 to 4.5 years, from 4 to 5 years, or from 4.5 to 5 years or more.

[0186] In some embodiments, the milk storage bag is configured to be stored at a temperature of about 0°C, about −2°C, about −4°C, about −8°C, about −10°C, about −12°C, about −14°C, about −16°C, about −18°C, or about −20°C or lower. In some embodiments, the milk storage bag is configured to be stored at a temperature of at least 0°C, at least −2°C, at least −4°C, at least −8°C, at least −10°C, at least −12°C, at least −14°C, at least −16°C, at least −18°C, or at least −20°C or lower. In some embodiments, the milk storage bag is configured to be stored at a temperature below −20°C. In some embodiments, the milk storage bag is configured to be stored at a temperature of at least −30°C, at least −40°C, at least −50°C, at least −60°C, at least −70°C, or at least −80°C. In some embodiments, the milk storage bag is configured to be stored at a temperature below −80°C. In some embodiments, the milk storage bag is configured to be deep-frozen. In some embodiments, the milk storage bags are configured to be stored in liquid nitrogen.

[0187] In some embodiments, the milk storage bag is configured to be stored at a temperature of 4° C. In some embodiments, the milk storage bag is configured to be stored at a temperature of about 2° C., about 4° C., about 6° C., about 8° C., about 10° C., about 12° C., about 14° C., or at least about 16° C. or higher. In some embodiments, the milk storage bag is configured to be stored at a temperature of at least 2° C., at least 4° C., at least 6° C., at least 8° C., at least 10° C., at least 12° C., at least 14° C., or at least about 16° C. or higher.

[0188] In some embodiments, the milk storage bag is configured to be stored at room temperature.

[0189] (kit) Furthermore, this specification provides kits.In some embodiments, kits contain the compositions disclosed herein in suitable containers, and if necessary, also include instructions for use in the methods disclosed herein.In some embodiments, compositions are prepared as concentrated liquid, tablets, powder, or single-use sachets.In some embodiments, kits include measuring spoons.

[0190] In some embodiments, the kits include sterile devices capable of delivering pre-filled amounts of the compositions disclosed herein. Non-limiting examples include vials and syringes.

[0191] In some embodiments, the kit further comprises at least one device disclosed herein. In some embodiments, the kit further comprises at least one milk storage container disclosed herein. In some embodiments, the kit comprises at least one device disclosed herein and at least one milk storage container.

[0192] (Example) These examples are for illustrative purposes only and are not intended to limit the scope of the claims set forth herein.

[0193] Example 1: Glycerol accumulation in human milk Eight human milk samples were tested to determine whether glycerol, a by-product of lipolysis, accumulates after storage. Human milk samples were collected from the same donor between 1 and 7 months of age, frozen, and then thawed for testing. Samples were frozen on the same day as collection. Glycerol was measured at 1 day (fresh), 33 days, 107 days, 122 days, 148 days, 157 days, 177 days, or 196 days after storage at -20°C. The samples were thawed, and the presence of glycerol was measured by bioluminescence using the Glycerol-Glo™ Assay (Promega; Catalog Number: J3150), a glycerol-dependent photoluminescence reaction, according to the manufacturer's instructions. Buffer solutions containing 0 μM or 100 μM glycerol and organic whole milk (cow) were used as controls. Glycerol content (bioluminescence) was measured using a BioTek Synergy Neo2 Hybrid Multimode Reader (Agilent; catalog number: BTNE02).

[0194] Results: The glycerol content of fresh human milk was slightly higher than that of organic whole milk (cow's milk). The amount of glycerol in human milk began to increase significantly after 33 days of storage, reaching a maximum at 107 days of storage, similar to the value of the control sample containing 100 μM glycerol. Therefore, compared with pasteurized milk, which does not significantly accumulate glycerol under the same / all test conditions, human milk significantly accumulates glycerol, a by-product of lipolysis, under frozen storage conditions. Glycerol and the free fatty acids produced simultaneously with it are by-products of lipolysis and remain in human milk after thawing (Figure 1), affecting the freshness and nutritional value of the milk and causing rancidity.

[0195] Example 2. Compound screening for lipolysis inhibitors in archived human milk. Approximately 2,700 compounds (from biolog phenotype microarrays, food additive libraries, and food-derived compound libraries) were spiked into fresh human milk, and each sample was stored at -20°C for 1 week. Samples were thawed at room temperature, and lipolysis was measured using Lipase, EnzChek™ Lipase Substrate, Green Fluorescence, 505 / 515 (Thermo Fisher; catalog number: E33955) kit, and BODIPY-fatty acid conjugates using a plate reader according to the manufacturer's instructions. Compounds with RFUs <400 were defined as hits. Surprisingly, only 24 of the approximately 2,700 compounds significantly inhibited lipase activity and lipolysis (Figure 2). These compounds include Tween 80, isoginkgetin, itaconic acid, methyl pyruvate, butyric acid, myricetin, ginkgetin, 2'-deoxyinosine, N-acetyl-neuraminic acid, Tween 20, Tween 40, chondroitin sulfate C, L-diencholic acid, glycyl-L-proline, laminarin, Tween 40, pectin, tetramethylene sulfone, 2'-deoxyadenosine, sorbic acid, and d-aminovaleric acid. These compounds are related to pectin, surfactants, glycosaminoglycans, and flavonoids. All compounds tested are listed in Tables 1 through 6. [Table 1] TIFF2026507501000003.tif199140 [Table 2] TIFF2026507501000005.tif199140 [Table 3] TIFF2026507501000007.tif199140 [Table 4] TIFF2026507501000009.tif199140 [Table 5] TIFF2026507501000011.tif 199140 TIFF2026507501000012.tif 199140 TIFF2026507501000013.tif 199140 TIFF2026507501000014.tif 199140 TIFF2026507501000015.tif 199140 TIFF2026507501000016.tif 199140 TIFF2026507501000017.tif 199140

Table 6

[0196] Example 3: Determination of Lipase Inhibitory Activity, Glycerol Content, and Antioxidant Retention by Validation of Single Compounds from Screening and Known Compounds Candidate compounds were selected from the screening and tested against other sources of compounds (Table 7). The compounds in Table 7 were added to fresh human milk and stored at -20°C for one week. Samples were thawed at room temperature, and lipolysis was measured as described in Example 2. Selected compounds were also assayed for glycerol as described in Example 1. Additionally, total antioxidant capacity was measured for selected compounds using a Total Antioxidant Capacity: Total Antioxidant Capacity Assay Kit (Abcam; catalog number: ab65329) according to the manufacturer's instructions, and the results are presented as a relative ratio to fresh human milk. Table 7 shows the results of lipase, glycerol, and total antioxidant capacity assays for single compounds. Lipase was considered inhibited when RFU < 400, glycerol was considered inhibited when RLU < 150,000, and total antioxidant capacity was considered maintained when the ratio was > 0.75. The results shown in Table 7 are for vitamins C, E, and carbonate / bicarbonate at a concentration of 500 mg / ml. All other compounds were assayed at 20 mg / ml. Additionally, all compounds were tested for lipase and antioxidant activity at multiple dilutions. Vitamins C, E, and carbonate / bicarbonate were tested at concentrations of 20 mg / ml, 10 mg / ml, 5 mg / ml, 2.5 mg / ml, 1.25 mg / ml, 0.625 mg / ml, and 0.313 mg / ml. All other compounds were tested at concentrations of 500 μg / ml, 250 μg / ml, 125 μg / ml, 62.5 μg / ml, 31.25 μg / ml, 15.6 μg / ml, and 7.8 μg / ml. Representative results for lipase interactions are shown in Figure 3A for xanthan gum, SureGel (infant thickener), laminarin, fucoidan, chondroitin sulfate, sunflower lecithin, apple pectin, low-methoxylated pectin, vitamin C, and vitamin E alone. Representative results for antioxidant capacity are shown for stored pectin in Figure 3B. All compounds were tested at 10 mg / ml followed by repeated two-fold dilutions. Vitamin C was tested at 350 μg / ml followed by repeated two-fold dilutions, and vitamin E was tested at 15 μg / ml followed by repeated two-fold dilutions (Figure 3).

[0197] Results: Surprisingly and unexpectedly, various compounds known for their use in the preservation and quality improvement of dairy products, such as surfactants and emulsifiers, which reduce interfacial tension between the oil and water phases and inhibit lipase-fat contact, did not inhibit lipase or glycerol activity as expected. Carbonates and bicarbonates act as buffers to inhibit acidification, a process known to delay rancidity and frequently incorporated into home-delivery dairy products. Surprisingly, these compounds, when administered alone, had no effect on lipase or glycerol activity in human milk samples. GelMix Infant Thickener is an infant formula containing three ingredients: tapioca maltodextrin, carob gum, and calcium carbonate. This product thickens liquids and had no effect on lipolysis in the human milk samples tested. Ultrasperse M, a cold-water-expanded (CWS) modified food starch extracted from waxy corn, used for refrigerated storage of frozen foods and food stabilization, was also tested. This product did not stabilize (i.e., inhibit lipase) the human milk samples tested. Inulin, a plant-derived dietary fiber with emulsifying properties, did not inhibit or slow the lipolysis of human milk as expected. Finally, lecithin is a food-safe surfactant and emulsifier added to everyday dairy products and current infant formulas. Lecithin alone did not inhibit lipolysis. Surprisingly, pectin and several different sources of pectin subunits inhibited lipase and / or glycerol production but did not affect total antioxidant capacity. Furthermore, vitamin C and vitamin E had no effect on lipase inhibition but maintained the total antioxidant capacity of milk. Finally, the surfactants Tween 20™ and Tween 80™ reduced lipase and glycerol production (Table 7 and Figure 3). [Table 7] TIFF2026507501000053.tif199140TIFF2026507501000054.tif199140TIFF2026507501000055.tif199140

[0198] Example 4: Examination of synergistic effects of selected compounds Compounds that demonstrated activity against either lipase, glycerol, and / or antioxidant capacity were further tested to evaluate synergistic effects. The compounds tested are shown in Table 8 under the test conditions described in Example 3. Additionally, lysozyme activity was measured using the EnzChek™ Lysozyme Assay Kit (Thermo Fisher; Catalog No. E22013) and protease activity was measured using the EnzChek™ Protease Assay Kit (Thermo Fisher; Catalog No. E6638) according to the manufacturer's instructions. Lysozyme and protease activity results are presented relative to fresh human milk. Table 7 shows the results for lipase, glycerol, total antioxidant capacity, lysozyme activity, and protease activity at the time of testing. Lipase was considered inhibited when RFU < 400, glycerol production was considered inhibited when RLU < 150,000, total antioxidant capacity was considered maintained when the ratio was > 0.75, lysozyme activity was considered maintained when the ratio was > 0.75, and protease activity was considered maintained when the ratio was > 0.75. All compounds were tested at 500 μg / ml, 250 μg / ml, 125 μg / ml, 62.5 μg / ml, 31.25 μg / ml, 15.6 μg / ml, and 7.8 μg / ml, and vitamins C and E were tested at 20 mg / ml, 10 mg / ml, 5 mg / ml, 2.5 mg / ml, 1.25 mg / ml, 0.625 mg / ml, and 0.313 mg / ml, respectively. Additionally, combinations of vitamin C and vitamin E were tested: low-methoxy pectin + vitamin C + vitamin E, sunflower lecithin + vitamin C + vitamin E, and sunflower lecithin + vitamin C + vitamin E + low-methoxy pectin (Figure 3A). All compounds were tested at 10 mg / ml and then tested in two-fold dilutions. Vitamin C was tested at 350 mg / ml and then tested in two-fold dilutions, and vitamin E was tested at 15 mg / ml and then tested in two-fold dilutions (Figure 3A).

[0199] Results: Table 8 shows the results of the combination tests at 500 μg / ml for all test compounds except vitamin C and vitamin E, which are shown at 20 mg / ml. Surprisingly, previously known commercial compounds (e.g., lecithin, inulin, and Ultrasperse M) did not exhibit synergistic effects with any of the compounds in the combination tests, nor did these known compounds enhance the activity of the newly identified compounds. Furthermore, an unexpected finding was that pectin, vitamin C, and vitamin E unexpectedly exhibited synergistic effects. Specifically, vitamin C and vitamin E, alone or in combination, did not inhibit lipase but maintained antioxidant capacity (Tables 7 and 8). On the other hand, pectin alone (Table 7) inhibited lipase but had no effect on maintaining antioxidant capacity. The three compounds demonstrated a synergistic effect of inhibiting lipase and maintaining total antioxidant capacity (Table 8).

[0200] Furthermore, Figure 3A shows that the combination of pectin, vitamin C, and vitamin E exhibits a synergistic effect on lipase activity compared to vitamins C and E alone or combinations without pectin. Pectin improves the lipase inhibitory effect of the combination of sunflower lecithin, vitamin C, and vitamin E compared to sunflower lecithin, vitamin C, and vitamin E without pectin (Figure 3A).

[0201] Therefore, these results demonstrate that the compositions of the present invention are useful for storing human milk. [Table 8]

[0202] Example 5: Comparative study of different types of pectin and galacturonic acid and their derived compounds Following the method described in Example 2, the lipase inhibitory activity of different types and origins of pectin and galacturonic acid was tested. The compounds tested were apple pectin (Sigma), apple pectin (TUOTAI), citrus pectin, lemon juice powder, apple peel powder, pectin (low methoxy), galacturonic acid, digalacturonic acid, trigalacturonic acid, and apple pectin (TUOTAI) + vitamin C + vitamin E. These compounds were added to fresh human milk, and all samples were stored at -20°C for 1 week. All pectins and galacturonic acid were at a concentration of 10 mg / ml, followed by seven two-fold dilutions. Vitamin C was at 350 μg / ml, followed by seven two-fold dilutions. Vitamin E was at 150 μg / ml, followed by seven two-fold dilutions. The results showed that the most effective compound for inhibiting lipase activity was apple pectin (TUOTAI) + vitamin C + vitamin E, with the different pectins showing different activity (Figure 4).

[0203] Therefore, these results indicate that different pectin sources have different effects on the inhibition of lipase activity and storage of human milk.

[0204] Example 6: Verification of the efficacy of a combination of pectin, vitamin C, and vitamin E in multiple donors A blend of apple pectin (TUOTAI) + vitamin C + vitamin E was mixed with fresh human milk from 14 different donors and stored / frozen at -20°C. Samples were stored for 1 week, and lipolysis and lipase inhibition were measured as described in Example 2. Samples were treated without the blend and then with increasing concentrations of 0.06%, 0.13%, 0.25%, and 1% pectin, 22 μg / ml, 44 μg / ml, 88 μg / ml, 176 μg / ml, and 352 μg / ml of vitamin C, and 11 μg / ml, 22 μg / ml, 44 μg / ml, 88 μg / ml, and 176 μg / ml of vitamin E, respectively. Lipase activity decreased dose-dependently during storage in each sample from different donors (Figure 5).

[0205] Thus, these results demonstrate that the compositions of the present invention preserve the nutritional value, integrity, and overall structure of multiple human milk samples from different donors.

[0206] Example 7: Effect of pectin or gum on lipase activity, glycerol content, and antioxidant retention Candidate gums and pectins commonly used as thickeners in infant foods were selected (Table 9). The compounds in Table 9 were added to fresh human milk, and the samples were stored at -20°C for 1 week. The samples were thawed at room temperature, and lipolysis was measured as described in Example 2, glycerol as described in Example 1, and total antioxidant capacity as described in Example 3. Table 9 and Figure 6 show the effect of each compound on lipase, glycerol, and total antioxidant capacity in human milk. Lipase was inhibited when RFU < 400, glycerol was inhibited when RLU < 150,000, and total antioxidant capacity was maintained when the ratio was > 0.75. The results shown in Table 9 and Figures 6A-6C correspond to a dose of 0.5% w / v (5 mg) per ml of human milk.

[0207] Results: The tested gums are used to the same extent as pectin as thickeners in infant foods. Antioxidant activity did not vary between the tested gums and pectin (Table 9 and Figure 6C). Surprisingly, the tested pectin inhibited lipolysis and glycerol production, whereas the tested gums had no effect (Table 9 and Figures 6A-6B).

[0208] Thus, these results indicate that although pectin and gums are widely used as thickeners in infant foods (e.g., infant formula), pectin has unexpected properties compared to other common thickeners, such as inhibiting lipolysis and glycerol production in human milk. [Table 9]

[0209] Example 8: Evaluating the efficacy of a combination of pectin, vitamin C, and vitamin E in unpasteurized human milk compared to pasteurized human milk One milliliter of unpasteurized human milk (raw human milk control; "raw milk") and human milk sterilized by batch pasteurization ("BP"), high-temperature short-time pasteurization ("HTST"), ultra-high-pressure pasteurization ("UHT"), or ultra-pasteurization ("UP") were treated with a combination of 5 mg Pacific LM-104 pectin, 0.1014 mg vitamin C, and 0.00406 IU (2.7 μg) vitamin E, or left untreated. After treatment or untreatment, samples were stored and frozen at -20°C for one week.

[0210] Batch sterilization was performed in accordance with the FDA Grade "A" Pasteurized Milk Regulations (2011). Specifically, 1 ml of human raw milk was transferred to a microcentrifuge tube and heated to 63°C in a water bath for 30 minutes. The tube was then removed and immediately cooled in an ice bath. High-temperature, short-time sterilization was performed in accordance with the FDA Grade "A" Pasteurized Milk Standards (2011). 1 ml of human raw milk was transferred to a microcentrifuge tube and heated to 72°C in a water bath for 15 seconds. The tube was then removed and immediately cooled in an ice bath. Ultra-high-temperature sterilization was performed according to the method described by Lewis MJ et al. (2012). 1 ml of human raw milk was transferred to a microcentrifuge tube and heated to 138°C in a water bath for 2 seconds. The tube was then removed and immediately cooled in an ice bath. Ultra-low-temperature sterilization was performed in accordance with the FDA Grade "A" Pasteurized Milk Regulations (2011). One ml of human raw milk was transferred to a microcentrifuge tube and heated to 90°C in a water bath for 1 second, and the tube was removed and immediately cooled in an ice bath.

[0211] All samples were thawed and lipolysis was measured as described in Example 2, glycerol as described in Example 1, and total antioxidant capacity as described in Example 3. Table 10 and Figure 7 show the effect of lipase, glycerol, and total antioxidant capacity in pasteurized and untreated human milk, comparing untreated with formulation treatments. Lipase was considered inhibited at RFU < 400, glycerol was considered inhibited at RLU < 150,000, and total antioxidant capacity was considered maintained at a ratio > 0.75.

[0212] Results: Total antioxidant capacity did not change between treated and untreated groups (Table 10). Lipase and glycerol were significantly reduced in the untreated sterilized samples compared to the untreated unpasteurized raw milk samples (Figure 7A and Figure 7D). However, lipase and glycerol levels were similarly reduced in the unpasteurized raw milk and sterilized samples (Figure 7B and Figure 7E). The amount of lipase in the unpasteurized raw milk samples was 6-fold lower than in the untreated unpasteurized raw milk samples (Figure 7C), and the amount of glycerol was approximately 41-fold lower than in the untreated unpasteurized raw milk samples (Figure 7F).

[0213] Thus, these results indicate that the tested formulation is specifically effective on unpasteurized human milk compared to milk that has already been pasteurized, providing an option to extend the shelf life of human milk without pasteurization. [Table 10]

[0214] Example 9: Evaluating the efficacy of a pectin, vitamin C, and vitamin E blend in unpasteurized human milk and unpasteurized cow's milk One milliliter of unpasteurized human milk and one milliliter of unpasteurized fresh milk (Mom's Organic Market) were treated with or without a blend of 5 mg Pacific LM-12 pectin, 0.1014 mg vitamin C, and 0.00406 IU (2.7 μg) vitamin E. After treatment, samples were stored frozen at -20°C for one week.

[0215] All samples were assayed for lipolysis as described in Example 2, glycerol as described in Example 1, and total antioxidant capacity as described in Example 3. Table 11 and Figure 8 show the effect of lipase, glycerol, and total antioxidant capacity in raw human milk compared to raw milk treated with the formulations. Lipase was considered inhibited at RFU<400, glycerol was considered inhibited at RLU<150,000, and total antioxidant capacity was considered maintained at a ratio >0.75.

[0216] Results: Total antioxidant capacity did not change between treated and untreated samples (Table 11). Lipase (Figure 8A-8B) and glycerol (Figure 8D-8E) levels were significantly reduced in treated, unpasteurized human milk compared with untreated, unpasteurized human milk. Surprisingly and unexpectedly, lipase (Figure 8A-8B) and glycerol (Figure 8D-8E) levels did not change in unpasteurized milk, regardless of treatment. In unpasteurized human milk, lipase levels were approximately 12-fold lower in treated samples compared with untreated samples (Figure 8C), and glycerol levels were approximately 6-fold lower in treated samples compared with untreated samples (Figure 8F).

[0217] These surprising and unexpected results therefore demonstrate that pectin containing vitamins C and E has the ability to inhibit lipase and glycerol production in human milk, but not in other dairy products such as cow's milk. Therefore, this formulation offers an unexpected option to extend freshness, nutritional value, and shelf life by preserving the lipids and preventing lipolysis unique to human milk, unlike other dairy products that require storage like other dairy products. [Table 11]

[0218] Example 10: Additive Effects of Pectin, Vitamin C, and Vitamin E on Lipolysis and Antioxidant Capacity To evaluate additive effects between formulation compositions, 5 ounces of unpasteurized human milk from three different donors were treated with either 0.5% w / v (0.735 g) Pacific LM-12 pectin, 15 mg vitamin C + 0.6 IU (0.402 mg) vitamin E, or 0.5% w / v (0.735 g) Pacific LM-12 pectin + 15 mg vitamin C + 0.6 IU (0.402 mg) vitamin E. Samples from each treatment were stored frozen at -20°C for 1 week after treatment.

[0219] All samples were thawed and lipolysis was measured as described in Example 2, and total antioxidant capacity was measured as described in Example 3. Fresh milk samples from each donor were also measured in the same way.

[0220] Results: Table 12 and Figure 9 show that pectin alone did not maintain antioxidant capacity, with levels similar to those observed in frozen, untreated samples. Pectin-treated samples required the addition of vitamins C and E to exhibit antioxidant capacity comparable to that of fresh human milk samples or samples treated with vitamins C and E alone. Vitamins C and E without pectin, on the other hand, maintained antioxidant activity but did not inhibit lipolytic activity. Treatment with pectin alone reduced lipase levels, and the addition of vitamins C and E had an additive effect, further inhibiting lipolysis compared to pectin alone (Table 12 and Figure 9).

[0221] Therefore, these results indicate that pectin requires the additive effects of vitamins C and E to maintain antioxidant capacity in human milk samples, while pectin alone is sufficient to inhibit lipolysis. [Table 12]

[0222] Example 11: Evaluation of Rancid Volatiles in Human Milk Treated with Pectin + Vitamin C + Vitamin E Headspace analysis was performed on 13 different human milk samples and one cow's milk sample, both untreated and treated with 0.5% w / v (0.735 g) Pacific LM-12 pectin, 15 mg vitamin C, and 0.6 IU (0.402 mg) vitamin E per 5 oz of milk sample. 100 μL of each sample was placed in a 20 ml headspace vial and 10 μL of 6 ppm phenyl-d5 acetate in water was added. Headspace collection was performed by solid-phase microextraction (SPME) using a DVB / carbon / PDMS arrowhead for 10 minutes at 40°C. Chromatographic analysis was performed using a Thermo Scientific ISQ Single Quadropole Gas Chromatograph-Mass Spectrometer equipped with a 30 m x 0.25 mm Stabilwax-DA capillary column. The analysis of the 28 samples was performed on three consecutive days (i.e., chromatographic runs), with approximately nine samples per run, to reduce sample processing time in the autosampler prior to analysis. In addition to the internal standard (fortified milk), each analysis included quality control samples, including empty vials (blanks). Chromatographic data were processed for peak alignment and determination of peak response for all observed volatiles (including the internal standard). Tentative peak identification was made for all reported volatiles based on match with the NIST mass spectral database.

[0223] Results: Table 13 and Figure 10 show that the combination of pectin, vitamin C, and vitamin E reduced the formation of volatile compounds in human milk samples compared to untreated samples. The reduction in volatile compounds such as pivalic acid, pelargonic acid, capric acid, and lauric acid translates to less rancidity, improved flavor, and improved odor in the treated human milk samples. [Table 13]

[0224] Example 12: Formulation 1: For preservation of human milk A formulation was prepared using the following materials: 0.5% w / v (5 mg) Pacific LM-12 pectin + 0.1014 mg vitamin C; and 0.00406 IU vitamin E (2.7 μg natural vitamin E or 1.8 μg synthetic vitamin E per ml of human milk). This formulation was added to 1 ml of human milk. Alternatively, a binder can be added to the formulation.

[0225] Example 13: Formulation 2: For preservation of human milk A formulation was prepared using the following materials: 5% w / v (0.735 g) Pacific LM-12 pectin, plus 15 mg of vitamin C, and 0.6 IU of vitamin E (0.402 mg natural vitamin E or 0.27 mg synthetic vitamin E) per 5 ounces (approximately 150 ml) of human milk. The formulation was added to 5 ounces (approximately 150 ml) of human milk. Alternatively, a binder (40 mg) can be added to the formulation.

[0226] Formulation 2 was molded into four different thicknesses using an LFA VICE handheld tablet press (Figure 11).

[0227] Example 14: Formulation 3: For preservation of human milk

[0228] A formulation was prepared using the following materials: 0.9% w / v (9 g) Pacific LM-12 pectin + 101.4 mg vitamin C and 4 IU vitamin E (2.68 mg natural vitamin E or 1.8 mg synthetic vitamin E) per 1000 ml of human milk. The formulation was added to 1000 ml of human milk. Alternatively, the formulation can include the addition of a binder (270.5 mg). ****

[0229] These examples are for illustrative purposes only and do not limit the scope of the claims provided herein.

[0230] While particular embodiments have been shown and described, it will be understood that changes and modifications may be made thereto in accordance with the level of skill of those skilled in the art without departing from the essential scope of the technology as defined in the following claims.

[0231] The embodiments illustratively described herein may suitably be practiced even in the absence of singular or plural elements, limitations, or restrictions not specifically disclosed herein. Thus, for example, terms such as "comprising," "including," and "containing" are to be interpreted broadly and without limitation. Furthermore, the terms and expressions used herein are used as descriptive terms and not as limiting. The use of these terms and expressions is not intended to exclude the disclosed features or equivalents thereof, but recognizes that various modifications are possible within the scope of the claimed technology. Furthermore, the phrase "consisting essentially of" is understood to include the elements explicitly recited and additional elements that do not materially alter the novel characteristics underlying the claims. The phrase "consisting of" excludes elements not explicitly recited.

[0232] The present disclosure is not limited to the specific examples described in this application. As will be apparent to those skilled in the art, many modifications and variations are possible without departing from the spirit and scope of the present disclosure. Functionally equivalent methods and compositions within the scope of the present disclosure include those recited herein, as well as those that would be apparent to those skilled in the art from the above description. Such modifications and variations are intended to be included within the scope of the appended claims. The present disclosure is limited only by the terms of the appended claims and the scope of equivalents to which such claims are entitled. It is to be understood that the present disclosure is not limited to different methods, compounds, or compositions, which may, of course, vary in many ways. Additionally, the terminology used herein is used only for the purpose of describing particular embodiments and is not intended to be limiting.

[0233] Furthermore, where features or aspects of the present disclosure are described using a Markush group, those skilled in the art will also understand that the present disclosure is also described in terms of individual elements or subgroups of elements of the Markush group.

[0234] As will be understood by those skilled in the art, for all purposes, particularly for purposes of providing a description herein, all ranges disclosed herein are intended to include all possible subranges and combinations of subranges, including the endpoints. Any range described can be readily recognized as fully describing and enabling the same range to be divided into at least equal halves, thirds, quarters, fifths, tenths, etc. As a non-limiting example, each range discussed herein can be readily divided into a lower third, middle third, upper third, etc. As will be understood by those skilled in the art, terms such as "up to," "at least," "greater than," "less than," etc., refer to ranges that are inclusive of the recited numerical values ​​and that can be divided into subranges as described above. Finally, as will be understood by those skilled in the art, a range includes each individual element.

[0235] All publications, patent applications, patents, and other documents referred to herein are deemed to be incorporated by reference in their entirety as if each were expressly incorporated individually. Definitions contained in the publications incorporated by reference are excluded to the extent they conflict with definitions herein.

[0236] Other embodiments are defined in the following claims.

Claims

1. at least one emulsifier, at least one antioxidant, at least one ice-structure-forming protein; at least one lipoprotein lipase (LPL) inhibitor protein; at least one small molecule lipase inhibitor; at least one milk stabilizing protein, at least one glycosaminoglycan, at least one flavonoid, or a combination thereof, A composition having at least one active ingredient selected from:

2. The composition of claim 1 , wherein the emulsifier is a surfactant, a protein, and / or a nanoparticle that functions as an emulsifier.

3. 10. The composition of claim 1, wherein the surfactant is a polysorbate, a citric acid ester of a monoglyceride or diglyceride, and / or a naturally occurring emulsifier.

4. 4. The composition of claim 3, wherein the naturally occurring emulsifier is lecithin and / or saponin-containing quillaja extract.

5. 5. The composition of claim 4, wherein the lecithin is derived from sunflower or soybean.

6. The composition of claim 1 , wherein the emulsifier is pectin.

7. The composition of claim 6, wherein the pectin is poly-D-galacturonic acid methyl ester.

8. 7. The composition of claim 6, wherein the pectin is apple pectin, citrus pectin, beet pectin, okra pectin, or kiwifruit pectin.

9. 9. The composition of claim 8, wherein the pectin is apple pectin.

10. The composition of claim 6, wherein the pectin is a low methoxy pectin or a high methoxy pectin.

11. 7. The composition of claim 6, wherein the pectin is a pectin subunit selected from galacturonic acid, digalacturonic acid, or trigalacturonic acid.

12. 7. The composition of claim 6, wherein the pectin is selected from GENU® Pectin Beta, GENU® Pectin LM-106 AS-YA, GENU® Pectin YM-100-L, Pacific RSND Pectin, Pacific LM-104 Pectin, or Pacific LM-12 Pectin.

13. 13. The composition of claim 12, wherein the pectin is Pacific LM-12 pectin.

14. The composition of any one of claims 6 to 13, wherein the amount of pectin is in the range of about 0.03 mg / ml to about 20 mg / ml.

15. The composition of any one of claims 6 to 13, wherein the amount of pectin is in the range of about 0.034 mg to about 9000 mg.

16. The composition of claim 2 , wherein the surfactant is a nonionic surfactant.

17. 2. The composition of claim 1, wherein the antioxidant is selected from vitamin C or a derivative thereof, vitamin E or a derivative thereof, a vitamin C-vitamin E mixture, ethylenediaminetetraacetate (EDTA) or a derivative thereof, phospholipids, egg yolk, or lambda-carrageenan.

18. 10. The composition of claim 1, wherein the at least one antioxidant is vitamin C, vitamin E, or vitamin A.

19. 19. The composition of claim 18, wherein the amount of vitamin C is in the range of about 0.6 μg / ml to about 350 μg / ml.

20. 19. The composition of claim 18, wherein the amount of vitamin C is in the range of about 0.6 μg to about 101 mg.

21. 19. The composition of claim 18, wherein the amount of vitamin E is in the range of about 0.01 μg / ml to about 150 μg / ml.

22. 19. The composition of claim 18, wherein the vitamin E is synthetic vitamin E in the range of 0.01 μg to about 1.8 mg, or natural vitamin E in the range of 0.01 μg to about 2.682 mg.

23. 2. The composition of claim 1, wherein the lipoprotein lipase (LPL) inhibitor protein is angiopoietin-like protein (ANGPTL) 3, 4, and / or 8.

24. 10. The composition of claim 1, wherein the milk stabilizing protein is lactoperoxidase.

25. 2. The composition of claim 1, wherein the glycosaminoglycan is selected from glucosamine sulfate, chondroitin sulfate, hyaluronic acid, heparan sulfate, or fucoidan.

26. 2. The composition of claim 1, wherein the flavonoid is selected from ginkgetin, isoginkgetin, myricetin, luteolin, or epigallocatechin gallate.

27. 10. The composition of claim 1, wherein the at least one active ingredient is not an antibody or a protein that binds to lipoprotein lipase (LPL).

28. 10. The composition of claim 1, wherein the at least one active ingredient is not a lipase inhibitor selected from GSK264220A, orlistat, RHC 80267, and Xen 445.

29. 29. The method of any one of claims 1 to 28, wherein the at least one active ingredient is not naturally present in human breast milk.

30. The composition according to any one of claims 1 to 29, wherein the composition preserves human milk.

31. (a) pectin, (b) Vitamin C, and (c) Vitamin E.

32. (a) pectin in the range of about 0.003% w / v to about 0.9% w / v; (b) pectin in the range of about 0.034 mg to about 9 mg; (c) pectin in the range of about 5 mg to about 1333 mg; or 32. The composition of claim 31, further comprising: (d) pectin in the range of about 34 mg to about 9000 mg.

33. 33. The composition of claim 32, wherein the pectin is selected from GENU® Pectin Beta, GENU® Pectin LM-106 AS-YA, GENU® Pectin YM-100-L, Pacific RSND Pectin, Pacific LM-104 Pectin, or Pacific LM-12 Pectin.

34. The pectin is Pacific LM-12 pectin.

35. (a) vitamin C in the range of about 0.676 μg to about 101 μg; (b) Vitamin C in the range of about 0.1 mg to about 15 mg; or 32. The composition of claim 31, further comprising: (c) vitamin C in the range of about 0.676 mg to about 101 mg.

36. (a) vitamin E in the range of about 0.0122 μg to about 1.8 μg; (b) Vitamin E in the range of about 1.8 μg to about 270 μg; or (c) Vitamin E in the range of about 0.01 mg to about 1.8 mg; 32. The composition of claim 31, wherein the vitamin E is synthetic vitamin E.

37. (a) vitamin E in the range of about 0.01 μg to about 2.68 μg; (b) Vitamin E in the range of about 2.68 μg to about 402 μg; or (c) Vitamin E in the range of about 0.01 mg to about 2.68 mg; 32. The composition of claim 31, wherein the vitamin E is natural vitamin E.

38. (a) Vitamin E in the range of about 0.0000271 IU to about 0.004 IU; (b) Vitamin E in the range of about 0.004 IU to about 0.27 IU; or 32. The composition of claim 31, further comprising: (c) Vitamin E in the range of about 0.01 IU to about 2.68 IU.

39. The composition of any one of claims 31 to 38, further comprising lecithin.

40. 40. The composition of any one of claims 31 to 39, further comprising one or more of a disintegrant, an adsorbent, a colorant, a flavoring agent, a sweetener, or a dispersing agent.

41. The composition of any one of claims 1 to 40, further comprising a binder.

42. The composition of any one of claims 1 to 41, wherein the composition is prepared in the form of a concentrate, a tablet, a powder, or a single-use sachet.

43. 43. The composition of any one of claims 1 to 42, wherein the composition reduces human milk lipase activity and maintains antioxidant capacity.

44. 44. The composition of any one of claims 1 to 43, for use in preventing rancidity, extending the storage life and / or maintaining the nutritional properties of human milk during storage.

45. 44. A method of preserving human milk comprising the steps of contacting human milk with the composition of any one of claims 1 to 43, and thereafter storing the human milk.

46. 46. ​​The method of claim 45, wherein the storing step comprises freezing the human milk at about -20°C.

47. 46. ​​The method of claim 45, wherein the storing step is performed at 4°C.

48. 48. The method of claim 46 or 47, wherein the storing step is carried out for about 1 day to about 5 years.

49. 49. The method of any one of claims 45 to 48, wherein the amount of human milk is in the range of about 1 ml to about 1000 ml.

50. 49. The method of any one of claims 45 to 48, wherein the amount of human milk is about 1 ml.

51. 49. The method of any one of claims 45 to 48, wherein the amount of human milk is about 5 ounces.

52. 49. The method of any one of claims 45 to 48, wherein the amount of human milk is about 150 ml.

53. The method according to any one of claims 30 to 44 and claims 45 to 52, wherein the human milk is expressed human milk or synthetic human milk.

54. 31. A device comprising a housing defining an interior volume of a space, said housing having at least one opening through which a substance within said interior volume of space can exit said housing and contact human milk or contact said human milk within said interior volume of space, said substance within said interior volume of space comprising a composition according to any one of claims 1 to 30.

55. 55. The apparatus of claim 54, wherein the apparatus is configured to be placed within a milk collection or storage container.

56. 55. The apparatus of claim 54, wherein the milk collection container or the storage container is a bag.

57. 55. The device of claim 54, wherein the device is configured to have an inlet and an outlet, and the device is configured to be positioned between a milk pump and a milk storage container such that all human milk must pass through the inlet and the outlet before entering the milk storage container.

58. A milk storage container having the composition according to any one of claims 1 to 44 fixed to the inner surface of the container.

59. 59. A milk storage container according to claim 58, wherein the container is made of plastic.

60. 59. The milk storage container of claim 58, wherein the bag is configured for storage at about -80°C to about 4°C, or at room temperature.

61. 59. The milk storage container of claim 58, wherein the bag is configured for storage for between about 1 day and about 5 years.

62. A kit comprising the composition of any one of claims 1 to 42, and optionally instructions for use.

63. 63. A kit according to claim 62, comprising the device according to any one of claims 54 to 57 or the milk storage container according to any one of claims 58 to 59.

64. 49. The method of any one of claims 45 to 48, wherein the amount of human milk is about 1000 ml.

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