Nutritional composition for improving blood sugar and blood fat and application thereof

Abstract

The invention provides a nutritional composition for improving blood sugar and blood fat and application of the nutritional composition. A nutritional composition helpful for maintaining blood fat and / or blood sugar health levels comprises the following essential components: a colostrum component and a casein hydrolytic peptide component; optionally, in the nutritional composition, the mass ratio of the colostrum component to the casein hydrolyzed peptide component is (500-0.1): (0.1-100). All the components in the nutritional composition provided by the invention have a synergistic effect, and the nutritional composition can be suitable for various foods for maintaining the health level of blood fat and / or blood sugar.

Description

Technical Field

[0001] The invention belongs to the field of food and relates to a nutritional composition, and more specifically, to a nutritional composition for improving blood sugar and lowering blood lipids and an application thereof. Background Art

[0002] There is an urgent need for people who do not suffer from hyperlipidemia (such as healthy people) or for other non-therapeutic purposes to maintain healthy levels of blood lipids (cholesterol / triglycerides). And hyperlipidemia is also a common disease that plagues middle-aged and elderly people. With age, endocrine function declines, and blood lipid levels rise accordingly. The risk of hyperlipidemia in middle-aged and elderly people is much higher than that in young people. It is worth noting that diseases such as diabetes, kidney disease, cholelithiasis, and some drugs (such as hypoglycemic drugs, diuretics, oral contraceptives, etc.) may also cause lipid metabolism disorders and lead to secondary hyperlipidemia. Traditional treatments mostly control blood lipids through oral lipid-lowering drugs and restricted diets, which also limits the diversity of patients' nutritional intake.

[0003] Maintaining healthy blood sugar levels for people who do not have diabetes (such as healthy people) or other non-therapeutic purposes has received increasing attention. In addition, the current situation of diabetes is severe. It is worth noting that the incidence of diabetes rises with age, and 98% of patients are middle-aged and elderly. Diabetes and its complications not only cause a double blow to the patient's body and mind, but also bring a heavy burden to the family, seriously threatening life and health. Therefore, the prevention and control of diabetes has become an urgent problem that society needs to solve. Traditional treatments mostly use diet control, oral hypoglycemic drugs and insulin injections. Although they can control blood sugar, they limit the richness of the patient's food intake and bring many inconveniences and pains.

[0004] Bovine colostrum contains precious active immunoglobulins (IgG, IgA, IgM, IgE, IgD) and rich milk calcium, protein, various trace elements and other nutrients. Studies have found that bovine colostrum is rich in immunoglobulins, which can directly improve the body's immune ability, supplement the deficiencies of the immune system, reduce the chances of respiratory and gastrointestinal infections, and promote the development of children's brains, bones, and teeth, so that children can thrive and grow up healthily.

[0005] Casein hydrolyzed peptides contain a variety of essential amino acids for the human body. They can supplement protein and provide adequate nutritional support for the body. Not only that, they can also actively promote the healthy development of bones, enhance the body's immunity, and significantly improve the absorption rate of calcium.

[0006] However, the prior art and products do not mention the effect of the combined formulation of bovine colostrum and casein hydrolyzed peptide composition on blood sugar and blood lipids, especially the combined formula does not involve the ratio. Summary of the invention

[0007] Problem that the invention aims to solve

[0008] Since the prior art and products do not mention the effect of using bovine colostrum and casein hydrolyzed peptide combination on hypoglycemia, especially the ratio is not mentioned in the combination formula. After a large number of experiments, the present invention optimizes the formula combination and ratio, and prepares a nutritional composition that maintains healthy blood sugar and / or blood lipid levels (e.g., lowers blood sugar and blood lipids) for the characteristics of the middle-aged and elderly, meeting the market demand for its functional composition.

[0009] To solve the above problems, the present invention evaluates the effect of colostrum and casein hydrolyzed peptide composition on lowering blood sugar and blood lipids through experiments. By scientifically matching colostrum and casein hydrolyzed peptide components to prepare a nutritional composition, it is possible to improve abnormal blood sugar and blood lipids.

[0010] Solutions for solving problems

[0011] [1] A nutritional composition that helps maintain healthy levels of blood lipids and / or blood glucose, wherein the nutritional composition comprises the following essential components: a colostrum component and a casein hydrolyzed peptide component; optionally, in the nutritional composition, the mass ratio of the colostrum component to the casein hydrolyzed peptide component is (500-0.1):(0.1-100).

[0012] [2] The nutritional composition according to [1], wherein the mass ratio of the colostrum component to the casein hydrolyzed peptide component in the nutritional composition is (200-0.5):(0.5-100).

[0013] [3] The nutritional composition according to [1] or [2], wherein the colostrum component includes colostrum and / or colostrum powder, and optionally, the colostrum is derived from at least one of cattle, sheep, horses and camels; and the casein hydrolyzed peptide component includes casein hydrolyzed peptides.

[0014] [4] The nutritional composition according to [3], wherein the protein component in the casein hydrolyzed peptide has the following molecular weight distribution:

[0015] (i) the content of peptide protein components with a relative molecular weight of less than 10,000 Da is 10% by mass or more;

[0016] The content is the content of the protein component in condition (i) based on dry weight relative to the total protein component in the casein hydrolyzed peptides.

[0017] [5] Use of a composition containing two essential ingredients, colostrum and casein hydrolyzed peptides, in the preparation of a nutritional composition that helps maintain healthy blood lipid and / or blood glucose levels.

[0018] [6] The use according to [5], wherein the nutritional composition inhibits the activity of α-glucosidase, alleviates insulin resistance, improves insulin sensitivity, restores glucose consumption capacity, increases the expression of gene PI3K and / or increases the expression of gene AKT; and / or the nutritional composition reduces lipid deposition in hepatocytes and / or increases the activity of lipoprotein lipase.

[0019] [7] A food comprising or using the nutritional composition according to any one of [1] to [4].

[0020] [8] The food according to [7], wherein the food is a nutritional food, a functional food or a health product, and optionally, the food includes pasta, a beverage, a reconstituted food, a baked pastry, a sauce or a functional nutritional supplement.

[0021] [9] Use of a composition containing two essential ingredients, colostrum and casein hydrolyzed peptide, in the preparation of food that helps maintain healthy blood lipid and / or blood glucose levels.

[0022]

[10] The use according to [9], wherein the food inhibits the activity of α-glucosidase, relieves insulin resistance, improves insulin sensitivity, restores glucose consumption capacity, and increases the expression of gene PI3K and / or gene AKT; and / or the food reduces lipid deposition in hepatocytes, increases lipoprotein lipase activity and / or increases PPAR-α gene expression.

[0023] Effects of the Invention

[0024] The present inventors unexpectedly found in experiments that the composition of specific composition provided in the present application can be used to improve abnormal blood sugar and blood lipid conditions.

[0025] After a large number of experiments, the present invention optimizes the formula combination and proportion to prepare a nutritional composition for improving insulin resistance, lowering blood sugar and blood lipids. Compared with general compositions, the combination of the two can synergistically improve and exert the greatest effect. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Figure 1 Schematic diagram of the MTT toxicity results of two nutrients on HepG2. DETAILED DESCRIPTION

[0027] Various exemplary embodiments, features and aspects of the present invention will be described in detail below. The word "exemplary" used here means "used as an example, embodiment or illustrative". Any embodiment described here as "exemplary" is not necessarily interpreted as being superior or better than other embodiments.

[0028] In addition, in order to better illustrate the present invention, numerous specific details are provided in the following specific embodiments. It should be understood by those skilled in the art that the present invention can be implemented without certain specific details. In other examples, methods, means, equipment and steps well known to those skilled in the art are not described in detail in order to highlight the subject matter of the present invention.

[0029] Unless otherwise stated, the units used in this specification are all international standard units, and the numerical values ​​and numerical ranges appearing in the present invention should be understood to include the inevitable systematic errors in industrial production.

[0030] In this specification, the word "may" means both performing a certain process and not performing a certain process.

[0031] In this specification, the references to "some specific / preferred embodiments", "other specific / preferred embodiments", "embodiments", etc., mean that the specific elements (e.g., features, structures, properties and / or characteristics) described in connection with the embodiments are included in at least one embodiment described herein, and may or may not exist in other embodiments. In addition, it should be understood that the elements may be combined in various embodiments in any suitable manner.

[0032] In the present invention, "Da" is used to represent the unit of molecular weight "Dalton", that is, "Dalton".

[0033] In this specification, the numerical range expressed using "a numerical value A to a numerical value B" means a range including the endpoints numerical values ​​A and B.

[0034] In the present invention, the term "about" is used to define the numerical range and parameters of the present invention are approximate values, and the specific relevant values ​​are presented as accurately as possible. Unless otherwise expressly stated, it should be understood that all ranges, quantities, values ​​and percentages used in the present invention are modified by "about". Here, "about" usually means that the actual value is within ±3%, ±2%, ±1% or ±0.5% of a particular value or range.

[0035] In the present specification, a numerical range expressed using "above" or "below" means a numerical range including the number.

[0036] In this specification, the word "may" means both performing a certain process and not performing a certain process.

[0037] In this specification, the use of "optional" or "optional" indicates that certain substances, components, execution steps, application conditions and other factors are used or not used.

[0038] In the present invention, "infant" is used to refer to a human group of 0 to 6 months old.

[0039] In the present invention, "older infants" are used to refer to a human group of 6 to 12 months of age.

[0040] In the present invention, the term "infant" is used to refer to a human group of 12 to 36 months old.

[0041] In the present invention, "infants" are used to refer to a human group under the age of 3.

[0042] In the present invention, the term "children" used herein refers to a human living group that is older than 3 years old and younger than 12 years old and is in the growth and development stage.

[0043] In this specification, the term "adult" refers to a person over the age of 18 years.

[0044] In this specification, the term "youth" refers to people aged 7-40 years old.

[0045] In this specification, the term "middle-aged people" refers to people aged 41-65 years old.

[0046] In this specification, the term "elderly" or "elderly person" refers to a person over the age of 65 years.

[0047] <Nutritional Composition>

[0048] In a first aspect of the present invention, a nutritional composition for improving blood sugar and blood lipids is provided, wherein the nutritional composition comprises the following essential components: a colostrum component and a casein hydrolyzed peptide component. The nutritional composition exhibits a significant synergistic effect, significantly controls and effectively maintains healthy blood sugar and / or blood lipid levels, such as reducing the blood sugar level and blood lipid content of the human body.

[0049] Compared with colostrum and casein hydrolyzed peptides alone, the nutritional composition provided by the present invention can synergistically maintain healthy levels of blood sugar and / or blood lipids, such as reducing blood sugar levels and blood lipid content in the human body. In some embodiments, the mass ratio of the colostrum component to the casein hydrolyzed peptide component is (500-0.1): (0.1-100). For colostrum and casein hydrolyzed peptides, when the content ratio of the two is within the above range, the relevant effect is particularly prominent.

[0050] The technical solution of the present invention is mainly obtained based on the following insights:

[0051] The present invention first verifies the safe dosage range of colostrum and casein hydrolyzed peptides from a (cell) biological perspective, and within this range, studies the biological performance of the two separately and in different dosage combinations. As a result, it is unexpectedly discovered that under a specific ratio, colostrum and casein hydrolyzed peptides can produce an obvious synergistic effect in lowering blood sugar and blood lipids in the human body.

[0052] (Casein hydrolyzed peptide fraction)

[0053] In the present invention, the casein hydrolyzed peptide component includes casein hydrolyzed peptides.

[0054] In this specification, casein is a calcium-phosphorus-containing binding protein that is acid-sensitive and precipitates at low pH. Casein is the main protein in the milk of mammals including cows, sheep and humans, and is also known as casein, casein and lactocasein.

[0055] There is no particular limitation on the source of the casein peptides of the present invention, and for example, the casein peptides may be hydrolyzates derived from various animal milks. Examples of such animal milks include cow's milk, goat's milk, horse's milk, camel's milk, and the like. In this specification, casein hydrolyzed peptides (also referred to as casein peptides in the present invention) refer to hydrolyzates obtained from casein and / or milk protein (optionally separated and purified) by biotechnological means such as enzymatic hydrolysis. Similarly, the casein peptides of the present invention may be self-made or commercially available.

[0056] In some embodiments, the protein components in the casein hydrolyzed peptides have the following molecular weight distribution:

[0057] (i) the content of peptide protein components with a relative molecular weight of less than 10,000 Da is 10% by mass or more;

[0058] The content is the content of the protein component in condition (i) based on dry weight relative to the total protein component in the casein hydrolyzed peptides.

[0059] In some specific embodiments, the protein components in the casein hydrolyzed peptides have the following molecular weight distribution:

[0060] (i) the content of peptide protein components with a relative molecular weight of less than 10,000 Da is 10% by mass or more, preferably 20% or more, more preferably 30% or more, for example 28% by mass, 29% by mass, 30% by mass, 31% by mass, 32% by mass, 33% by mass, 34% by mass, 35% by mass, 40% by mass, 45% by mass, etc.;

[0061] The content is the content of the protein component in condition (i) based on dry weight relative to the total protein component in the casein hydrolyzed peptides.

[0062] With this composition (degree of hydrolysis), casein hydrolyzed peptides can better synergize with colostrum in lowering blood sugar and blood lipids.

[0063] In some exemplary embodiments, the content of the peptide protein component with a relative molecular weight of less than 10,000 Da from casein hydrolyzed peptides is greater than 30% by mass.

[0064] (Colostrum components)

[0065] In the present invention, the colostrum component includes colostrum and / or colostrum powder.

[0066] In the present invention, the colostrum refers to the milk secreted within 72 hours after the birth of a healthy animal or prepared into a powder. There is no particular limitation on the source of the colostrum of the present invention in principle. In some embodiments, the colostrum can be bovine colostrum, sheep colostrum, camel colostrum, horse colostrum, etc.

[0067] In some embodiments, the colostrum may preferably be bovine colostrum.

[0068] In some embodiments, the bovine colostrum is milk from a cow within about 3 days after calving, or a raw material made from milk by low-temperature spray drying or freeze drying. When bovine colostrum is used in combination with casein hydrolyzed peptides, the nutritional composition achieves a better synergistic effect of maintaining healthy blood sugar and / or blood lipid levels, such as reducing blood sugar and blood lipids in the human body.

[0069] (Proportion)

[0070] In order to obtain better synergistic effects in maintaining healthy blood sugar and / or blood lipid levels, such as lowering the blood sugar level and blood lipid content of the human body, in some embodiments, in the nutritional composition, the mass ratio of the colostrum component to the casein hydrolyzed peptide component is (500-0.1):(0.1-100).

[0071] In some preferred embodiments, in the nutritional composition, the mass ratio of the colostrum component to the casein hydrolyzed peptide component is (200-0.5):(0.5-100).

[0072] In order to obtain further better synergistic effects in maintaining healthy blood sugar and / or blood lipid levels, such as lowering blood sugar and blood lipids, in some more preferred embodiments, in the nutritional composition, the mass ratio of the colostrum component to the casein hydrolyzed peptide component is (150-0.5):(0.5-100) or (100-0.5):(0.5-50). In some further preferred embodiments, in the nutritional composition, the mass ratio of the colostrum component to the casein hydrolyzed peptide component is (100-1):(0.5-20), and more preferably the mass ratio is (100-1):(1-10), (100-1):(1-7), (100-1):(1-5), (100-1):(1-3), (99-1):(1-10), (98-1):(1-10), (95-1):(1-10), (90-1):(1-10), (60-1):(1-10), (50-1):(1-10), (40-1):(1-10), (30-1):(1-10), (20-1):(1-10), (10-1):(1-10) or (5-1):(1-10).

[0073] In some exemplary embodiments, in the nutritional composition, the mass ratio of the colostrum component to the casein hydrolyzed peptide component is 100:1; 99:1; 98:2; 95:5; 50:1; 10:1; 9:1; 5:1; 4:1; 1:1; 1:2 or 1:10, and in some preferred embodiments, in the nutritional composition, the mass ratio of the colostrum component to the casein hydrolyzed peptide component is 100:1; 99:1; 98:2; 95:5; 50:1; 10:1; 9:1; 5:1; 4:1; 1:1; 1:2 or 1:10.

[0074] When the forearm component and the casein hydrolyzed peptide component are within the above range, the composition further obtains a better synergistic effect of maintaining healthy blood sugar and blood lipid levels, such as reducing the blood sugar level and blood lipid content of the human body. It can produce a significant synergistic effect in reducing blood sugar and blood lipids in the human body. In some specific embodiments, the blood sugar and blood lipid regulation is a non-therapeutic purpose.

[0075] In the present invention, the colostrum component and the casein hydrolyzed peptide component are used in combination, and unexpectedly, a synergistic effect can be found in maintaining healthy levels of blood sugar and blood lipids. In addition, it is also found that under the same conditions and proportions, the synergistic effect can also achieve the effect of regulating blood sugar and blood lipids when using relatively low concentrations of colostrum components and casein hydrolyzed peptide components.

[0076] (Form of composition and other components)

[0077] The nutritional composition of the present invention comprises at least the colostrum component and the casein hydrolyzed peptide component described above. There is no particular limitation on the method of forming the composition, which can be prepared by mixing the above-mentioned components in a solvent or by mixing two high-purity extracts.

[0078] In addition, there are no particular limitations on other components that may be used in the composition of the present invention. Without impairing the effects of the present invention, other edible ingredients, food additives or solvent components commonly used in the art may be used.

[0079] The nutritional composition of the present invention may be in a liquid form, or may be in a semi-solid form or a solid form.

[0080] When the nutritional composition of the present invention is in liquid form, in some preferred embodiments, the concentration of colostrum in the nutritional composition is 0-5 mg / mL. In some preferred embodiments, the concentration of casein hydrolyzed peptide in the nutritional composition is 0-5 mg / mL.

[0081] Colostrum and casein hydrolyzed peptides will not have negative effects on cells at this concentration. The two can synergistically enhance and significantly reduce the body's blood sugar level and blood lipid content.

[0082] In some more preferred embodiments, in the nutritional composition, the concentration of the colostrum is 0-2 mg / mL. In some further preferred embodiments, in the nutritional composition, the concentration of the colostrum is 0-1.5 mg / mL, more preferably the concentration of the colostrum is 10-1000 μg / mL, for example: the concentration of the colostrum is 10 μg / mL; 100 μg / mL; 500 μg / mL; 900 μg / mL; 950 μg / mL; 980 μg / mL; 990 μg / mL; 1000 μg / mL.

[0083] In some more preferred embodiments, in the nutritional composition, the concentration of the casein hydrolyzed peptides is 0-2 mg / mL. In some further preferred embodiments, in the nutritional composition, the concentration of the casein hydrolyzed peptides is 0-1.5 mg / mL, more preferably the concentration of the casein hydrolyzed peptides is 10-1000 μg / mL, for example: the concentration of the casein hydrolyzed peptides is 10 μg / mL; 20 μg / mL; 50 μg / mL; 100 μg / mL; 200 μg / mL; 500 μg / mL; 1000 μg / mL.

[0084] <Food>

[0085] The above composition of the present invention has been verified by experiments to improve the effects of PA-induced insulin resistance and OA-induced lipid deposition, indicating that the composition can reduce PA-induced insulin resistance and OA-induced lipid deposition, and thus can have a more obvious effect of regulating blood sugar and blood lipids, and therefore can be used as a food, functional health product or functional health supplement. Therefore, in the second aspect of the present invention, a food is provided, which contains or uses the nutritional composition described in the first aspect.

[0086] The food of the present invention can be a food suitable for maintaining healthy blood sugar levels (e.g., controlling blood sugar) and / or maintaining healthy blood lipid levels (e.g., lowering blood lipids) for healthy people, diabetics and / or patients with dyslipidemia such as hyperlipidemia.

[0087] In some specific embodiments, the food can be obtained by processing the nutritional composition described according to the first aspect above.

[0088] There is no particular limitation on the food of the present invention, and the food may generally be pasta, beverages, reconstituted food, baked goods, sauces or functional nutritional supplements.

[0089] Wheaten food may include staple foods processed or made from flour-based raw materials, coarse grain staple foods, etc., such as steamed bread, cakes, noodles, stuffed staple foods, etc.

[0090] For baked pastries, it can be baked cakes or biscuits mainly based on cream, eggs and baking powder.

[0091] There are no particular restrictions on beverages, which may be fruit drinks, vegetable drinks, milk tea drinks, tea drinks, milk, yogurt, vitamin drinks, etc. For fruit or vegetable drinks, in addition to the two functional components of the present invention, they may also include fruit or vegetable juice, or their solid components, etc. For vitamin drinks, in addition to the two components of the present invention, they mainly contain various functional vitamins and other functional ingredients, such as white sugar, sodium cyclamate, acesulfame potassium, taurine, potassium sorbate, lysine, inositol, vitamin pp, vitamin B6, vitamin B12, citric acid, etc.

[0092] Reconstituted foods may typically be reconstituted milk powder products, such as adult milk powder, middle-aged and elderly milk powder, and the like.

[0093] In addition, there are no special restrictions on functional nutritional supplement foods, which can be used as nutritional supplements or meal replacements. Such foods, in addition to the two functional components of the present invention, may also include one or more of the following components: plant product ingredients, animal dairy product ingredients, animal meat product ingredients, protein ingredients, vitamin supplements, mineral supplements, nucleotide supplements, polyunsaturated fatty acid supplements and any food-acceptable excipients.

[0094] Plants or plant extracts, including fruits such as figs, pomegranates, kiwis, tangerines, oranges, pineapples, strawberries, apples, rubber, grapes, pears, cherries, blueberries, blackberries, blackcurrants, cranberries, raspberries, melons, emblica chinensis and bilberry or their extracts; fruit and vegetable substances such as onions, cucumbers, tomatoes, cauliflower, carrots, spinach, kale, Brussels sprouts, garlic, basil, oregano or their extracts; grains such as rice (indica rice, japonica rice, glutinous rice), wheat (wheat, barley, oats, rye), corn, sorghum, millet, sorghum, yellow rice, buckwheat, soybeans, broad beans, peas, mung beans, red beans, kidney beans or their extracts; nuts such as walnuts, pistachios, cashews, hazelnuts, almonds, apricots, pine nuts, peanuts, melon seeds, chestnuts, macadamia nuts, ginkgo nuts or their extracts; coffee or its extracts.

[0095] Animal ingredients include meat products from beef, lamb, fish or poultry.

[0096] The fat component may include at least one of saturated fatty acids, polyunsaturated fatty acids, monounsaturated fatty acids, OPO structured lipids, DHA, EPA, ARA, and phospholipids. More specifically, the fat includes safflower seed oil, walnut oil, peanut oil, corn oil, soybean oil, argan oil, olive oil, tea oil, sacha inchi oil, olive oil, coconut oil, perilla oil, deep-sea fish oil, cocoa butter, palm oil, butter, cream, lard, medium-chain triglycerides or lecithin, etc.

[0097] Functional added components include vitamins (one or more of vitamin A, β-carotene, vitamin D3, vitamin E, vitamin K1, vitamin B1, vitamin B2, vitamin B6, vitamin B12, vitamin C, pantothenic acid, folic acid, niacin, choline, inositol, biotin), starch, modified starch, amino acids (L-lysine-L-glutamic acid, L-glutamic acid, L-arginine, L-tryptophan, L-glutamine, taurine, L-valine, L-isoleucine or L-leucine, etc.), traditional Chinese medicine or traditional Chinese medicine extracts, dietary fiber (inulin, konjac flour, galacto-oligosaccharides, fructo-oligosaccharides, isomalto-oligosaccharides, soybean polysaccharides, cyclodextrin, resistant dextrin or soybean fiber, etc.).

[0098] Trace element supplements may include metal ion salts of organic acids, such as one or more of calcium citrate, L-calcium lactate, calcium hydrogen phosphate, potassium gluconate, sodium citrate, ferrous gluconate, potassium iodide, zinc gluconate, sodium selenite, copper gluconate, chromium sulfate, manganese gluconate and magnesium gluconate.

[0099] Any food-acceptable excipients, including but not limited to solvents, antioxidants, antibacterial agents, thickeners, diluents, cosolvents, stabilizers, emulsifiers, fillers, disintegrants, lubricants, coating materials, anti-caking agents, flavoring agents, sweeteners, edible flavors, edible colorings, etc.

[0100] The specific form of the nutritional / health food of the present invention is not particularly limited, and may be solid (powder or block, etc.), semi-solid (soft, paste or thick, etc.) or liquid.

[0101] The present invention does not specifically limit the food that can be prepared using the above nutritional composition and has the effect of maintaining healthy blood sugar and / or blood lipid levels, such as reducing human blood sugar levels and blood lipid content. In some embodiments, the food is a solid dairy product or a liquid dairy product; for example, milk powder, cheese, yogurt, liquid milk, etc.

[0102] In some specific embodiments, the nutritional or health food can be a powdered reconstituted food (solid beverages, milk powder, instant coffee, cereal powder, nut powder or lotus root powder, etc.), a liquid beverage (carbonated beverages, fruit and vegetable juice beverages, functional beverages, tea beverages, milk beverages or alcoholic beverages, etc.).

[0103] Typically, the above-mentioned foods include: milk powder for pregnant women, milk powder for middle-aged and elderly people, or nutritional or dietary supplements, etc.

[0104] <Purpose>

[0105] The present invention also provides the use of a composition containing two essential ingredients, colostrum and casein hydrolyzed peptides, in preparing a nutritional composition that helps maintain healthy blood lipid and / or blood sugar levels. The present invention also provides the use of a composition containing two essential ingredients, colostrum and casein hydrolyzed peptides, in preparing a food that helps maintain healthy blood lipid and / or blood sugar levels.

[0106] In some embodiments, the nutritional composition or food product is effective in maintaining healthy blood glucose and / or blood lipid levels, such as lowering blood glucose levels and / or lowering blood lipid levels.

[0107] In some embodiments, maintaining healthy blood lipid and / or blood glucose levels is a non-therapeutic purpose of maintaining healthy blood lipid and / or blood glucose levels, that is, the composition containing the two essential components of colostrum and casein hydrolyzed peptides is not used for abnormal blood lipid or blood glucose caused by diseases (such as diabetes, hyperlipidemia, etc.).

[0108] In some specific embodiments, maintaining healthy blood sugar levels, for example, lowering blood sugar levels includes inhibiting the activity of α-glucosidase, alleviating insulin resistance, improving insulin sensitivity, restoring glucose consumption capacity, increasing the expression of gene PI3K and / or increasing the expression of gene AKT.

[0109] In some specific embodiments, maintaining healthy blood lipid levels, for example, lowering blood lipid levels includes reducing lipid deposition in hepatocytes, increasing lipoprotein lipase activity, and / or increasing PPAR-α gene expression.

[0110] In some embodiments, the specific selection and ratio of the colostrum and casein hydrolyzed peptides are as described above in <Nutritional Composition>.

[0111] Example

[0112] The embodiments of the present invention will be described in detail below in conjunction with the examples, but those skilled in the art will appreciate that the following examples are only used to illustrate the present invention and should not be considered to limit the scope of the present invention. If no specific conditions are specified in the examples, they are carried out according to normal conditions or the conditions recommended by the manufacturer. If the manufacturer is not specified for the reagents or instruments used, they are all conventional products that can be obtained commercially.

[0113] In the following Examples section, unless otherwise stated, the starting materials used were as follows.

[0114] Bovine colostrum: INGREDTA, U22425;

[0115] Casein hydrolyzed peptide: produced by Feihe.

[0116] The protein components in the casein hydrolyzed peptides have the following molecular weight distribution:

[0117] (i) the content of peptide protein components with a relative molecular weight of less than 10,000 Da is 30% by mass or more;

[0118] The content is the content of the protein component in condition (i) based on dry weight relative to the total protein component in the casein hydrolyzed peptides.

[0119] In the following sections, unless otherwise specified, when referring to the parts by mass and ratios of ingredients in the nutritional composition, the ratios refer to the mass ratios of bovine colostrum and casein hydrolyzed peptides.

[0120] Experimental procedures

[0121] 1. Experimental Materials

[0122] The experimental materials are shown in Table 1.

[0123] Table 1: Main reagents for the experiment

[0124]

[0125]

[0126]

[0127] 2. Experimental Equipment

[0128] The experimental equipment is shown in Table 2.

[0129] Table 2: Main instruments and equipment for the experiment

[0130]

[0131] 3. Cell Experiment

[0132] 1. HepG2 cell culture

[0133] HepG2 cells were maintained in DMEM complete medium containing 10% FBS at 37°C and 5% CO 2 Culture in a saturated humidity cell culture incubator, and change the medium every other day. When the confluence is greater than 85% during the logarithmic growth phase, the cells can be subcultured, washed twice with PBS, digested with 0.25% trypsin for 2 minutes, and then added with complete medium to terminate digestion, blow the cells until they are detached from the bottle wall, transfer them to a centrifuge tube, centrifuge at 1500rpm for 5 minutes, remove the supernatant and subculture at a ratio of 1:2. Take cells in the logarithmic growth phase for the experiment.

[0134] 2. Construction of HepG2 cell model

[0135] (1) Construction of HepG2 cell hyperlipidemia model

[0136] HepG2 cells were cultured in 24-well plates in low-glucose DMEM complete medium containing 10% FBS at 37°C and 5% CO 2 After the cells are cultured in a saturated humidity cell culture incubator until the number reaches 90% and they become adherent cells, they are replaced with high-glucose DMEM complete medium containing 10% FBS for culture. The test substance is intervened in the cells for 4 hours in advance, and then 0.3mM sodium oleate (OA) is added for treatment for 16 hours. After 16 hours, the high-lipid modeling of the cells is completed, and the cells can be collected for testing of different indicators.

[0137] (2) Construction of HepG2 cell insulin resistance model

[0138] HepG2 cells were placed in a 24-well culture plate and low-glucose DMEM complete medium containing 10% FBS, and cultured in a 37°C, 5% CO2 saturated humidity cell culture incubator until the number reached 90%. After becoming adherent cells, they were replaced with serum-free high-glucose DMEM medium for starvation operation for 12 hours, and the supernatant was discarded again. After replacing with new serum-free high-glucose DMEM medium, the test substance was intervened in the cells for 4 hours in advance, and then 0.3mM palmitate (PA) was added for treatment for 24 hours. After 24 hours, the high-glucose modeling of the cells was completed, and the cells could be collected for testing of different indicators.

[0139] 3. MTT cell activity assay

[0140] HepG2 cells were digested with trypsin to prepare single-cell suspension, and 200 μL / well of the cell suspension was inoculated into 96-well flat-bottom culture plates (3×10 4 cells / well), 37°C, 5% CO 2 After the cells were completely attached to the wall, the culture medium was discarded, and the cells were washed with PBS buffer 1-2 times. 20 μL / well of culture medium containing different concentrations of bovine colostrum (0-4.0 mg / mL) and / or casein hydrolyzed peptide (0-4.0 mg / mL) of the samples to be tested were added. Each group had 3 wells. A blank control group (normal HepG2 cell culture without the samples to be tested) was set up at 37°C and 5% CO. 2 After 12 hours of incubation in the incubator, the original culture medium was discarded, and 20 μL / well of 5 g / L MTT solution was added in a dark place. After 4 hours of incubation, the MTT solution was discarded, and 150 μL DMSO was added. The plate was fully shaken for 10 minutes on an ELISA analyzer, and the absorbance was measured at 490 nm after the purple precipitate was dissolved to monitor cell activity and screen the optimal safe concentration of the monomer test substance.

[0141] The cell survival rate (C) was calculated according to formula (1): C = X 1 / X 0 ×100%

[0142] (1) Where: X 1 Indicates the optical density (OD) value of the sample group; X 0 It represents the OD value of the blank control group.

[0143] 4. Cell Viability Detection

[0144] Prepare a single cell suspension of HepG2 hepatocytes by placing approximately 1×10 4Cells were inoculated in a 96-well plate and cultured until the cells occupied about 85% of the wells. The sample to be tested was intervened (performed according to the nutrient combination and dosage determined by 2. MTT cell activity assay in experimental step 3). After 12 hours of intervention with the sample to be tested, 10 μL of CCK8 solution was added to each well of the plate using a pipette. After incubation in a 37°C constant temperature incubator for 4 hours, the absorbance at 450 nm was measured using a microplate reader.

[0145] IV. Blood sugar lowering cell experiment

[0146] (I) In vitro α-glucosidase inhibitory activity test

[0147] Thoroughly mix 20 μL of the test solution (the concentration of each test substance determined by the CCK8 experiment in step 3. Cell viability detection in experimental step 3) with 20 μL of α-glucosidase solution (0.3 U / mL) and 140 μL of PBS buffer (0.2 M). After reacting at 37°C for 20 min, add 20 μL of 3 mmol / L pNPG solution. After reacting at 37°C for 15 min, add 80 μL of Na 2 CO 3 The reaction was terminated with a solution (0.5 mol / L), and acarbose was used as a positive control. The method used for the positive control was consistent with the method for the test substance, and the test substance solution was replaced with a 10 μg / mL acarbose solution. The α-glucosidase inhibition rate was calculated according to the following formula:

[0148] α-Glucosidase inhibition rate = [1–(B1–B2) / (B3–B4)] × 100%

[0149] Where: B1 is the absorbance of the sample group;

[0150] B2 is the absorbance of the sample background group;

[0151] B3 is the absorbance of the blank group;

[0152] B4 is the absorbance of the blank background group.

[0153] (II) Preparation of long-chain fatty acid esters

[0154] Sodium palmitate was dissolved in 6 mL of high-glucose DMEM and heated in a 75°C water bath until completely dissolved. When the solution temperature dropped to about 50°C, an equal volume of 10% (w / v) BSA was added for conjugation dissolution. After ultrasonication for 10 min, oscillation and mixing were performed for 10 min to allow the fatty acid to completely combine with BSA to form fatty acid-BSA (prepared concentration: 10 mmol / L). The fatty acid ester was filtered and sterilized using a 0.22 μm filter membrane for later use.

[0155] (III) Cellular glucose consumption detection

[0156] HepG2 cells were cultured in 24-well plates in low-glucose DMEM complete medium containing 10% FBS at 37°C and 5% CO 2 After culturing in a saturated humidity cell culture incubator until the number reaches 90% and the cells become adherent cells, the medium is replaced with serum-free high-glucose DMEM medium for starvation operation for 12 hours, the supernatant is discarded again, and the new serum-free high-glucose DMEM medium is replaced. The sample to be tested is intervened in the cells for 4 hours in advance, and then 0.3mM palmitate is added for treatment for 24 hours. The supernatant of the culture fluid is aspirated, and the glucose content of the supernatant of the culture fluid is measured to reflect the glucose consumption. The measurement is performed according to the instructions of the kit, and the glucose consumption is used to feedback the degree of insulin resistance of the cells. The lower the glucose consumption, the more aggravated the insulin resistance, and the higher the glucose consumption, the less insulin resistance.

[0157] (IV) Real-time quantitative polymerase chain reaction (qRT-PCR)

[0158] After analyzing and treating insulin-resistant HepG2 cells, RNA was extracted using a total RNA extraction kit and reverse transcribed into cDNA. Primers were synthesized for PI3K and AKT. Fluorescence was detected by qRT-PCR using a kit, and mRNA levels were normalized to GAPDH expression.

[0159] 1. RNA Extraction

[0160] (1) After the cells were taken out from -80°C, 350 μL of lysis buffer RLA and 10 μL of proteinase K were added.

[0161] (Proteinase K), vortex to mix until cells are loose, and let stand at room temperature for 5 minutes. The sample becomes viscous, indicating that lysis is complete.

[0162] (2) Transfer the cell lysate to the gDNA removal column and centrifuge at 12,000 g for 5 minutes until all the liquid flows out into the collection tube below. If a small amount of liquid remains, centrifuge again.

[0163] (3) Add an equal volume of 70% ethanol to the collection tube from the previous step, mix well, transfer to the RNA adsorption column, centrifuge at 12,000 g for 1 minute, and discard the effluent.

[0164] (4) Add 700 μL of deproteinized solution RW3 to the RNA adsorption column, centrifuge at 12,000 g for 1 min, and discard the effluent; add 500 μL of rinse solution RW to the RNA adsorption column, centrifuge at 12,000 g for 1 min, and discard the effluent; add 500 μL of RW to the RNA adsorption column again, centrifuge at 12,000 g for 1 min, and discard the effluent; put the RNA adsorption column back into the centrifuge, centrifuge at 12,000 g for 2 minutes, and open the lid to dry.

[0165] (5) Add 70 μL of RNase-free water to the RNA adsorption column and transfer it to a new EP tube. After standing at room temperature for 1 minute, centrifuge at 12,000 g for 1 minute and collect the eluate, which is the RNA solution.

[0166] (6) Add 99 μL ddHO to the 96-well plate. 2 O, 1 μL RNA solution, and the absorbance was measured at 260 nm by a microplate reader.

[0167] 2.RT Reverse Transcription

[0168] (1) gDNA removal

[0169] The system configuration is as follows:

[0170]

[0171] The PCR instrument program is as follows:

[0172]

[0173] (2) Reverse transcription

[0174] The system configuration is as follows:

[0175]

[0176] The PCR instrument program is as follows:

[0177]

[0178]

[0179] (3) cDNA storage

[0180] Place the product from the previous step on ice temporarily. For long-term storage, store it at -20℃ or -80℃.

[0181] 3. qPCR Quantification

[0182] (1) Primer sequence

[0183]

[0184] (2) Prepare the following qPCR reaction system using cDNA as template:

[0185]

[0186] After preparation, mix well, centrifuge, add to the 96-well Roche fluorescent quantitative PCR plate, and then put it into the fluorescent quantitative PCR instrument for reaction;

[0187] (3) qPCR reaction procedure:

[0188] Two-step method

[0189]

[0190]

[0191] Melting curve program:

[0192] (4) Three replicate wells were prepared for each sample, and the relative expression level of the corresponding sample was calculated using the 2^(-△△CT) method.

[0193] 5. Lipid-lowering Cell Experiment

[0194] (I) Preparation of long-chain fatty acid esters

[0195] Sodium oleate was dissolved in 6 mL of high-glucose DMEM and heated in a 75°C water bath until completely dissolved. When the solution temperature dropped to about 50°C, an equal volume of 10% (w / v) BSA was added for conjugation dissolution. After ultrasonication for 10 min, oscillation and mixing were performed for 10 min to allow the fatty acid to completely combine with BSA to form fatty acid-BSA (preparation concentration: 10 mmol / L). The fatty acid ester was filtered and sterilized using a 0.22 μm filter membrane for later use.

[0196] (II) Determination of triglyceride content

[0197] HepG2 cells were cultured in 24-well plates in low-glucose DMEM complete medium containing 10% FBS at 37°C and 5% CO 2 After the cells were cultured in a saturated humidity cell culture incubator until the number reached 90% and they became adherent cells, they were replaced with high-glucose DMEM complete medium containing 10% FBS for culture. The samples to be tested were intervened in the cells for 4 h in advance, and then 0.3 mM sodium oleate was added for treatment for 16 h. After the intervention, the culture medium was discarded, the cells were washed twice with PBS solution, and the PBS was discarded. Triglyceride lysis solution was added to break the cells, and the triglyceride content was measured according to the instructions.

[0198] (III) Lipoprotein lipase (LPL) activity detection

[0199] HepG2 cells were cultured in 24-well plates in low-glucose DMEM complete medium containing 10% FBS at 37°C and 5% CO 2 The cells were cultured in a saturated humidity cell culture incubator until the number reached 90% and they became adherent cells. Then, the cells were cultured with high-glucose DMEM complete medium containing 10% FBS. The samples to be tested were intervened in the cells for 4 h in advance, and then 0.3 mM sodium oleate was added for treatment for 16 h. After the intervention, the culture medium was discarded, the cells were washed twice with PBS solution, and the PBS was discarded. Then, the LPL kit was used for detection according to the instructions.

[0200] (IV) Real-time quantitative polymerase chain reaction (qRT-PCR)

[0201] After the intervention of the test sample was completed, RNA was extracted and reverse transcribed into cDNA. Primers were synthesized for PPAR-α. qRT-PCR was performed using a kit to detect fluorescence, and mRNA levels were normalized to GAPDH expression.

[0202] 1. RNA Extraction

[0203] (1) After the cells are taken out from -80℃, add 350μL of lysis buffer RLA and 10μL of proteinase K, vortex and mix until the cells are loose, and let stand at room temperature for 5 minutes. The sample becomes viscous, indicating that the lysis is complete.

[0204] (2) Transfer the cell lysate to the gDNA removal column and centrifuge at 12,000 g for 5 minutes until all the liquid flows out into the collection tube below. If a small amount of liquid remains, centrifuge again.

[0205] (3) Add an equal volume of 70% ethanol to the collection tube from the previous step, mix well, transfer to the RNA adsorption column, centrifuge at 12,000 g for 1 minute, and discard the effluent.

[0206] (4) Add 700 μL of deproteinized solution RW3 to the RNA adsorption column, centrifuge at 12,000 g for 1 min, and discard the effluent; add 500 μL of rinse solution RW to the RNA adsorption column, centrifuge at 12,000 g for 1 min, and discard the effluent; add 500 μL of RW to the RNA adsorption column again, centrifuge at 12,000 g for 1 min, and discard the effluent; put the RNA adsorption column back into the centrifuge, centrifuge at 12,000 g for 2 minutes, and open the lid to dry.

[0207] (5) Add 70 μL RNase-free water to the RNA adsorption column and transfer it to a new EP tube.

[0208] After standing at room temperature for 1 minute, centrifuge at 12000g for 1 minute and collect the eluate, which is the RNA solution. (6) Add 99 μL ddHO to the 96-well plate. 2 O, 1 μL RNA solution, and the absorbance was measured at 260 nm by a microplate reader.

[0209] 2.RT Reverse Transcription

[0210] (1) gDNA removal

[0211] The system configuration is as follows:

[0212]

[0213] The PCR instrument program is as follows:

[0214]

[0215] (2) Reverse transcription

[0216] The system configuration is as follows:

[0217]

[0218] The PCR instrument program is as follows:

[0219]

[0220] (3) cDNA storage

[0221] Place the product from the previous step on ice temporarily. For long-term storage, store it at -20℃ or -80℃.

[0222] 3. qPCR reaction

[0223] (1) Primer sequence

[0224]

[0225] (2) Prepare the following qPCR reaction system using cDNA as template:

[0226]

[0227] After preparation, mix well, centrifuge, add to the 96-well Roche fluorescent quantitative PCR plate, and then put it into the fluorescent quantitative PCR instrument for reaction;

[0228] (3) qPCR reaction procedure:

[0229] Two-step method

[0230]

[0231] Melting curve program:

[0232]

[0233] (4) Three replicate wells were prepared for each sample, and the relative expression level of the corresponding sample was calculated using the 2^(-△△CT) method.

[0234] VI. Experimental dose

[0235] According to the experimental requirements, the cell experiment examples and comparative examples were determined, and the specific combinations and dosage arrangements are shown in Table 3 below:

[0236] Table 3: Cell experiment dosage

[0237]

[0238]

[0239] “—” means that it is not added or there is no proportional relationship.

[0240] The OA model is a HepG2 cell hyperlipidemia model induced by oleic acid to accumulate triglycerides;

[0241] The PA model is an insulin resistance model constructed by inducing HepG2 cells with palmitate.

[0242] In the present specification, the above-mentioned model is used to simulate abnormal blood sugar and blood lipids, and the abnormalities include abnormalities that do not reach the disease state.

[0243] 7. Statistical Analysis

[0244] The results are expressed as mean ± standard deviation (n = 3), and SPSS software was used for One-way ANOVA test. When p < 0.05, it was judged to be significantly different, when p < 0.01, it was judged to be extremely significantly different, and when p < 0.001, it was extremely significantly different. In addition, "*" is used to indicate P < 0.05, "**" is used to indicate P < 0.01, and "***" is used to indicate P < 0.001.

[0245] Test Case

[0246] Test Example 1: Screening of safe doses of each sample for HepG2 cells

[0247] This test case mainly investigated the MTT toxicity of two initial nutrients to HepG2, including bovine colostrum and casein hydrolyzed peptides. The experimental results are as follows Figure 1 As shown:

[0248] Depend on Figure 1 Based on the data in , and combined with specific experimental operations, we can see that:

[0249] (1) Bovine colostrum did not show obvious MTT toxicity within the range of investigation.

[0250] (2) Casein peptides cannot be completely dissolved in water, ethanol and DMSO systems. Adding sodium hydroxide can increase their solubility. Their cytotoxicity can be ignored within the concentration range studied.

[0251] Test Example 2: Effects of each sample on CCK8 cell viability

[0252] After determining each dose group, the CCK8 kit was used to first investigate their effects on the cell viability of HepG2 cells. The data on their effects on cell viability are shown in Table 4.

[0253] Table 4: Effects of various examples on HepG2 cell viability

[0254]

[0255] a The drug used in the OA positive control group was simvastatin (0.03 mM).

[0256] b The drug used in the PA positive control group was metformin (0.05 mM).

[0257] “—” means that it is not added or there is no proportional relationship.

[0258] According to the analysis of the experimental data results (Table 4), compared with the blank control group, the cell viability of the OA model control group, the PA model control group and the positive drug intervention group (OA positive control group, PA positive control group) did not show significant fluctuations, which shows that the constructed OA and PA models and their positive drugs have good biosafety. At the same time, the effects of each embodiment on the viability of HepG2 cells were investigated, and no significant adverse effects were found, and the cell viability was maintained above 90%.

[0259] Test Example 3: Effects of each sample on lowering blood sugar and results

[0260] 1. Inhibition rate of α-glucosidase by the nutritional composition

[0261] After confirming the biosafety of each group of examples, the insulin resistance model was constructed by inducing HepG2 cells with palmitate, and the inhibitory activity of the examples on α-glucosidase in vitro was first investigated. The inhibition data of bovine colostrum, casein hydrolyzed peptides and their nutritional compositions are shown in Table 5.

[0262] Table 5: Inhibition rate data of bovine colostrum, casein hydrolyzed peptides and their nutritional composition on α-glucosidase

[0263]

[0264] “—” means that it is not added or there is no proportional relationship.

[0265] The inhibition data of bovine colostrum, casein peptides and their nutritional compositions on α-glucosidase show (Table 5) that bovine colostrum alone has no obvious inhibitory effect on α-glucosidase, casein peptides have a certain inhibitory effect on α-glucosidase, and the inhibitory effect of high-concentration casein peptides is more obvious. In addition, bovine colostrum and casein peptides also have a synergistic effect on the inhibition of α-glucosidase activity, and the inhibition rate of the nutritional composition of the two on α-glucosidase is greater than the sum of the inhibition rates of the two.

[0266] 2. Determination of Glucose Consumption in Cell Model

[0267] The insulin resistance model was constructed by inducing HepG2 cells with palmitate. Compared with the blank control group, the formation of insulin resistance in the model group led to a decrease in the consumption of glucose in the supernatant by cells. In order to evaluate the alleviating effect of nutrients and their compositions on the insulin resistance model, this test case adopted a pretreatment method of early intervention to systematically examine the effects of these substances on improving insulin sensitivity and restoring glucose consumption capacity, and the metformin-treated group was used as a positive control group.

[0268] The glucose consumption in the supernatant of bovine colostrum, casein hydrolyzed peptide and the nutritional composition thereof is shown in Table 6.

[0269] Table 6: Glucose consumption data of the supernatant of bovine colostrum, casein hydrolyzed peptides and their nutritional compositions

[0270]

[0271]

[0272] Wherein, “—” indicates no addition or no proportional relationship, “*” indicates P < 0.05, “**” indicates P < 0.01, and “***” indicates P < 0.001.

[0273] Insulin resistance will cause the rate at which cells consume glucose to decrease. The degree of cellular insulin resistance can be reflected by detecting the amount of cellular glucose consumption. If the glucose consumption is low, the degree of cellular insulin resistance is high, and if the glucose consumption is high, the degree of insulin resistance is low.

[0274] The results shown in Table 6 show that different dosages of the exemplary bovine colostrum / casein hydrolyzed peptide nutritional composition have all-improving effects on insulin resistance patterns.

[0275] In terms of the components and dosages used, Example 6 is equivalent to the combination of cell experiment comparative examples 3 and 5. Compared with the model control group, comparative examples 3 and 5 increased glucose consumption by 0.05 and 1.98, while cell experiment Example 6 increased glucose consumption by 2.57, which is greater than the sum of the first two, 2.03.

[0276] In terms of the components and dosages used, the experimental dosages of Comparative Examples 4 (bovine colostrum alone) and 7 (casein hydrolyzed peptide alone) are 1000 μg / mL, and Examples 9-14 are bovine colostrum + casein hydrolyzed peptide combined dosages of 1000 μg / mL. It can be found that the increments of glucose consumption in Examples 9-14 are all greater than the increment of 1.41 in Comparative Example 4 (bovine colostrum alone) and the increment of 0.71 in Comparative Example 7 (casein hydrolyzed peptide alone). This shows that the combination of the two has a significant effect compared to the addition of a single substance.

[0277] Test case 4: Genetic analysis

[0278] PI3K (phosphatidylinositol-3-kinase) and AKT (protein kinase B) are key components of the insulin signaling pathway, which play a vital role in insulin sensitization and metabolic homeostasis regulation. In the insulin resistance (IR) HepG2 cell model, decreased activity or impaired function of the PI3K and AKT signaling pathways are often observed. This test aims to explore the mechanism of action of a specific nutritional composition in maintaining healthy blood sugar levels in the IR-HepG2 cell model through in-depth analysis at the genetic level.

[0279] 1. Relative expression of PI3K gene

[0280] The relative expression levels of PI3K gene in bovine colostrum, casein hydrolyzed peptide and nutritional composition thereof are shown in Table 7.

[0281] Table 7: Relative expression of PI3K gene in bovine colostrum, casein hydrolyzed peptides and nutritional compositions thereof

[0282]

[0283] Wherein, “—” indicates no addition or no proportional relationship, “*” indicates P < 0.05, “**” indicates P < 0.01, and “***” indicates P < 0.001.

[0284] As shown in Table 7, compared with the model control group, the nutritional composition can restore the normal function of the PI3K signaling pathway, improve the signal transmission efficiency of insulin in HepG2 cells, and increase the uptake and utilization of glucose, and is expected to be used to reverse insulin resistance and restore the normal metabolic function of cells. In addition, the inventors surprisingly found that when bovine colostrum and casein hydrolyzed peptides are used in combination, they have a synergistic effect on restoring the normal PI3K signaling pathway. In particular, according to cell experiment examples 1, 3, 4, and 7, it can be seen that:

[0285] In terms of the components and dosages used, Example 1 is equivalent to the combination of cell experiment comparative examples 2 and 5. Compared with the model control group, comparative examples 2 and 5 increased the relative expression of PI3K gene by 0.52 and 0.02, respectively, while cell experiment example 1 increased the relative expression of PI3K gene by 0.64, which is greater than the sum of the first two, 0.54.

[0286] Example 3 is equivalent to the combination of cell experiment comparative examples 4 and 7. Compared with the model control group, comparative examples 4 and 7 increased the relative expression of PI3K gene by 0.19 and 0.11 respectively, while cell experiment example 3 increased the relative expression of PI3K gene by 0.66, which is greater than the sum of the first two 0.3.

[0287] This conclusion can also be drawn from Examples 4 and 7.

[0288] In terms of the components and dosages used, the experimental dosages of Comparative Examples 4 (bovine colostrum alone) and 7 (casein hydrolyzed peptide alone) are 1000 μg / mL, and Examples 9-14 are bovine colostrum + casein hydrolyzed peptide combined dosages of 1000 μg / mL. It can be found that the increments of the relative expression of the PI3K gene in Examples 9-14 are all greater than the increment of 0.19 in Comparative Example 4 (bovine colostrum alone) and the increment of 0.11 in Comparative Example 7 (casein hydrolyzed peptide alone). This shows that the combination of the two is more effective than the addition of a single substance.

[0289] 2. Relative expression of AKT gene

[0290] The relative expression levels of AKT gene in bovine colostrum, casein hydrolyzed peptide and nutritional composition thereof are shown in Table 8.

[0291] Table 8: Relative expression of AKT gene in bovine colostrum, casein hydrolyzed peptides and nutritional compositions thereof

[0292]

[0293] Wherein, “—” indicates no addition or no proportional relationship, “*” indicates P < 0.05, and “***” indicates P < 0.001.

[0294] As shown in Table 8, compared with the model control group, the nutritional composition can restore the normal function of the AKT signaling pathway, improve the signal transmission efficiency of insulin in HepG2 cells, and increase the uptake and utilization of glucose, and is expected to be used to reverse insulin resistance and restore the normal metabolic function of cells. In addition, the inventors surprisingly found that when bovine colostrum and casein hydrolyzed peptides are used in combination, they have a synergistic effect on restoring the normal AKT signaling pathway. In particular, according to cell experiment examples 6 and 7, it can be seen that:

[0295] In terms of the components and dosages used, Example 6 is equivalent to the combination of cell experiment comparative examples 3 and 5. Compared with the model control group, comparative examples 3 and 5 increased the relative expression of the AKT gene by 1.17 and 0.15, respectively, while cell experiment Example 6 increased the relative expression of the AKT gene by 1.4, which is greater than the sum of the first two, 1.32.

[0296] Example 7 is equivalent to the combination of cell experiment comparative examples 4 and 5. Compared with the model control group, comparative examples 4 and 5 increased the relative expression of AKT gene by 0.39 and 0.15 respectively, while cell experiment example 7 increased the relative expression of AKT gene by 0.6, which is greater than the sum of the first two 0.54.

[0297] In terms of the components and dosages used, the experimental dosage of Comparative Examples 4 (bovine colostrum alone) and 7 (casein hydrolyzed peptide alone) is 1000 μg / mL, and the exemplary Examples 9 and 13 are bovine colostrum + casein hydrolyzed peptides with a combined dosage of 1000 μg / mL. It can be found that the increments of the relative expression of the AKT gene in Examples 9 and 13 are both greater than the increment of 0.39 in Comparative Example 4 (bovine colostrum alone) and the increment of 0.49 in Comparative Example 7 (casein hydrolyzed peptide alone). This shows that the combination of the two is more effective than the addition of a single substance.

[0298] Test Example 5: Results of the lipid-lowering experiment

[0299] 1. Determination of triglyceride content in cell models

[0300] A HepG2 cell hyperlipidemia model with triglyceride accumulation was constructed by inducing oleic acid, and simvastatin was used as a positive control drug. This test example will investigate whether the early intervention treatment of the nutritional composition can effectively improve the accumulation of triglycerides, thereby alleviating hyperlipidemia. The triglyceride accumulation of cells treated with bovine colostrum, casein hydrolyzed peptides and their nutritional compositions is shown in Table 9.

[0301] Table 9: Triglyceride accumulation in cells treated with bovine colostrum, casein hydrolyzed peptides and their nutritional composition

[0302]

[0303] Wherein, “—” indicates no addition or no proportional relationship, “**” indicates P < 0.01, and “***” indicates P < 0.001.

[0304] Triglycerides are formed by the esterification of glycerol and fatty acids and are the main component of blood lipids. Increased triglyceride accumulation in tissues and cells is closely related to obesity and fatty liver. The triglyceride detection kit can accurately measure the triglyceride content in tissue cells. The detection is corrected by protein. The higher the measured value, the higher the triglyceride level, and the lower the measured value, the lower the triglyceride content.

[0305] As shown in Table 9, the sample treatment results show that compared with the model control group, the combination of casein hydrolyzed peptides and bovine colostrum can significantly reduce OA-induced lipid deposition in HepG2 hepatocytes. This indicates that both components are helpful in improving blood lipids.

[0306] In terms of the components and dosages used, Example 4 is equivalent to the combination of cell experiment comparative examples 1 and 6. Compared with the model control group, comparative examples 1 and 6 reduced the intracellular triglyceride content by 12.03 and 16.27, respectively, while Example 4 reduced the intracellular triglyceride content by 29.02, which is greater than the sum of the first two, 28.3.

[0307] In terms of the components and dosages used, Example 6 is equivalent to the combination of cell experiment comparative examples 3 and 5. Compared with the model control group, comparative examples 3 and 5 reduced the intracellular triglyceride content by 7.75 and 20.17, respectively, while Example 6 reduced the intracellular triglyceride content by 31.67, which is greater than the sum of the first two, 27.92.

[0308] 2. Lipoprotein lipase (LPL) activity detection

[0309] In order to further evaluate the effects of nutrients and their compositions on the hyperlipidemia cell model, this test example measured the LPL enzyme activity of cells after different treatments. The LPL enzyme activity of cells treated with bovine colostrum, casein hydrolyzed peptides and their nutrient compositions is shown in Table 10.

[0310] Table 10: LPL activity data of cells treated with bovine colostrum, casein hydrolyzed peptides and their nutritional composition

[0311]

[0312] Wherein, “—” indicates no addition or no proportional relationship, “**” indicates P < 0.01, and “***” indicates P < 0.001.

[0313] The experimental results show (Table 10) that low doses of bovine colostrum, high doses of casein hydrolyzed peptides and certain specific nutritional compositions can significantly restore the LPL activity of cells. In terms of the components and dosages used, Example 1 is equivalent to the combination of cell experimental comparative examples 2 and 5. Relative to the model control group, comparative examples 2 and 5 increased the LPL activity of cells by -0.001 and 0.011, while Example 1 increased the LPL activity of cells by 0.015, which is greater than the sum of the first two by 0.01.

[0314] Example 2 is equivalent to the combination of cell experiment comparative examples 2 and 6. Compared with the model control group, comparative examples 2 and 6 increased the LPL activity of cells by -0.001 and 0.002, while example 2 increased the LPL activity of cells by 0.019, which is greater than the sum of the first two by 0.001.

[0315] 3. Analysis of PPAR-α gene expression

[0316] PPAR-α (peroxisome proliferator-activated receptor-α) is a gene that plays a key role in lipid metabolism. Oleic acid, as an unsaturated fatty acid, can induce a hyperlipidemic phenotype in HepG2 cells and activate lipid metabolism pathways. In oleic acid-induced hyperlipidemic HepG2 cells, the expression of PPAR-α is crucial. The activation of PPAR-α promotes lipid degradation. By studying the expression of PPAR-α in oleic acid-induced hyperlipidemic HepG2 cells intervened by nutritional compositions, we can better analyze its mechanism for alleviating hyperlipidemic symptoms.

[0317] The relative expression levels of PPAR-α gene in bovine colostrum, casein peptide and nutritional composition thereof are shown in Table 11.

[0318] Table 11: PPAR-α gene relative expression data of bovine colostrum, casein peptide and nutritional composition thereof

[0319]

[0320] Wherein, “—” indicates no addition or no proportional relationship, “*” indicates P < 0.05, “**” indicates P < 0.01, and “***” indicates P < 0.001.

[0321] As shown in Table 11, the results show that compared with the model control group, the exemplary nutritional composition can restore the normal function of the PPAR-α signaling pathway, improve lipid metabolism, and maintain the homeostasis of intracellular lipids. In addition, the inventors surprisingly found that when bovine colostrum and casein peptides are used in combination, they have a synergistic effect on restoring the normal function of the PPAR-α signaling pathway. In particular, according to cell experiment examples 3, 4, 5, 7, and 8, it can be seen that:

[0322] In terms of the components and dosages used, Example 3 is equivalent to the combination of cell experiment comparative examples 4 and 7. Compared with the model control group, comparative examples 4 and 7 increased the relative expression of PPAR-α gene by 0.19 and 0.04, respectively, while cell experiment Example 3 increased the relative expression of PPAR-α gene by 0.28, which is greater than the sum of the first two by 0.23 and greater than each of the first two.

[0323] In terms of the components and dosages used, Example 5 is equivalent to the combination of cell experiment comparative examples 3 and 7. Compared with the model control group, comparative examples 3 and 7 increased the relative expression of PPAR-α gene by 0.18 and 0.04, respectively, while cell experiment Example 5 increased the relative expression of PPAR-α gene by 1.08, which is greater than the sum of the first two by 0.22 and greater than each of the first two.

[0324] The same conclusion can be drawn from Examples 4, 7 and 8.

[0325] It can be seen that the present invention provides the effects of bovine colostrum and casein hydrolyzed peptide composition on lowering blood sugar and blood lipids, especially on improving PA-induced insulin resistance and OA-induced lipid deposition, which provides new ideas for the development of functional foods in the future. Bovine colostrum and casein hydrolyzed peptides have broad prospects in improving blood sugar and blood lipids in the body. The research of the present invention shows that in an in vitro model, HepG2 cells treated with a combination of casein hydrolyzed peptides and bovine colostrum have significantly improved insulin resistance and lipid deposition, and there is a good synergistic effect between the components.

[0326] It should be noted that, although the technical solution of the present invention is introduced with specific examples, those skilled in the art will appreciate that the present invention should not be limited thereto.

[0327] The embodiments of the present invention have been described above, and the above description is exemplary, not exhaustive, and is not limited to the disclosed embodiments. Many modifications and variations will be apparent to those of ordinary skill in the art without departing from the scope and spirit of the described embodiments. The selection of terms used herein is intended to best explain the principles of the embodiments, practical applications, or technical improvements in the market, or to enable other persons of ordinary skill in the art to understand the embodiments disclosed herein.

Claims

1. A nutritional composition that helps maintain healthy levels of blood lipids and / or blood sugar, characterized in that: The nutritional composition comprises the following essential components: a colostrum component and a casein hydrolyzed peptide component; Optionally, in the nutritional composition, the mass ratio of the colostrum component to the casein hydrolyzed peptide component is (500-0.1):(0.1-100).

2. The nutritional composition according to claim 1, characterized in that In the nutritional composition, the mass ratio of the colostrum component to the casein hydrolyzed peptide component is (200-0.5):(0.5-100).

3. The nutritional composition according to claim 1 or 2, characterized in that The colostrum component includes colostrum and / or colostrum powder, and optionally, the colostrum is derived from at least one of cattle, sheep, horses and camels; The casein hydrolyzed peptide component includes casein hydrolyzed peptides.

4. The nutritional composition according to claim 3, characterized in that The protein components in the casein hydrolyzed peptides have the following molecular weight distribution: (i) the content of peptide protein components with a relative molecular weight of less than 10,000 Da is 10% by mass or more; The content is the content of the protein component in condition (i) based on dry weight relative to the total protein component in the casein hydrolyzed peptides.

5. Use of a composition containing two essential ingredients, colostrum and casein hydrolyzed peptide, in preparing a nutritional composition that helps maintain healthy blood lipid and / or blood sugar levels.

6. The use according to claim 5, characterized in that: The nutritional composition inhibits the activity of α-glucosidase, alleviates insulin resistance, improves insulin sensitivity, restores glucose consumption capacity, increases the expression of gene PI3K and / or increases the expression of gene AKT; and / or The nutritional composition reduces lipid deposition in liver cells and / or increases lipoprotein lipase activity.

7. A food, characterized in that The food contains or uses the nutritional composition according to any one of claims 1 to 4.

8. The food according to claim 7, characterized in that The food is a nutritional food, a functional food or a health product; Optionally, the food includes pasta, beverages, reconstituted food, baked goods, sauces or functional nutritional supplements.

9. Use of a composition containing two essential ingredients, colostrum and casein hydrolyzed peptide, in preparing food that helps maintain healthy levels of blood lipids and / or blood sugar.

10. The use according to claim 9, characterized in that: The food inhibits the activity of α-glucosidase, alleviates insulin resistance, improves insulin sensitivity, restores glucose consumption capacity, increases the expression of gene PI3K and / or increases the expression of gene AKT; and / or The food reduces lipid deposition in liver cells, increases lipoprotein lipase activity and / or enhances PPAR-α gene expression.

Images