Use of active folate substance and nutritional composition containing active f folate substance

Abstract

The use of an active folate substance, a nutritional composition containing the active folate substance and N-acetylneuraminic acid, and a nutritional composition containing the active folate substance and fucosyllactose in the preparation of a food product that, when ingested by a mother during gestation and / or lactation, contributes to the growth of an offspring body and / or contributes to the antioxidant capacity of the offspring body.

Description

Uses of active folic acid substances and nutritional compositions containing active folic acid substances Technical Field

[0001] This invention belongs to the food field, specifically relating to the use of active folic acid substances and nutritional compositions containing active folic acid substances, and more specifically relating to the use of active folic acid substances and nutritional compositions containing active folic acid substances, when ingested by the mother, to help offspring grow and / or help offspring resist oxidation. Background Technology

[0002] Early life nutrition plays an irreplaceable role in overall health throughout life. A mother's adequate nutritional intake not only determines the quality of embryonic development but also profoundly impacts the growth and development of her offspring. Early life nutrition significantly influences implantation of the fertilized egg, cell differentiation, embryonic development, pregnancy outcome, child growth, intellectual development, learning ability, and disease resistance. Early life nutrition directly determines a child's physical growth, with birth weight often serving as an indicator of intrauterine nutritional status. Malnutrition in infancy and early childhood can lead to irreversible growth retardation, illness, and even death.

[0003] Folic acid is a B vitamin that the human body cannot synthesize and must be obtained through additional intake. As an important cofactor in one-carbon unit metabolism, folic acid mediates the de novo synthesis of purines and thymosin and regenerates homocysteine ​​(Hcy) into methionine, thus supporting a wide range of methylation reactions in the body, including DNA, proteins, and neurotransmitters. Folic acid deficiency can lead to impaired DNA synthesis, affecting cell division and reproduction. Low folic acid levels during pregnancy are associated with various birth defects in offspring, including neonatal respiratory distress syndrome (NRDS), congenital heart defects, growth retardation, and low birth weight. Folic acid and its metabolically related B vitamins are crucial for brain development and function in offspring during pregnancy. Reference 1 discloses a prenatal nutritional supplement containing L-methylfolate or L-methylfolate, arginine, and vitamin B12. L-methylfolate avoids the problem of folic acid absorption and conversion due to genetic defects, and also avoids adverse reactions caused by folic acid accumulation in the body when pregnant women cannot absorb and convert it. Arginine can promote blood circulation and effectively meet the needs of pregnant women for more semi-essential amino acids during pregnancy, preventing common pregnancy-related diseases such as gestational hypertension, eclampsia, and pregnancy depression. Furthermore, the combination of L-methylfolate and arginine has good compatibility.

[0004] N-acetylneuraminic acid, also known as sialic acid, is an acetylated derivative of acidic glyconeuraminic acid. Sialic acid is abundant in the brain, milk, blood, and nerve tissue mucoproteins of mammals, with the highest concentration in the brain. It is an important structural and functional component of gangliosides. Studies have shown that due to significant differences in the content and structure of sialic acid between cow's milk and breast milk, breastfed infants score higher overall in cognitive development than formula-fed infants. N-acetylneuraminic acid in breast milk plays a crucial role in promoting the development of the nervous system and enhancing immunity in infants and young children. Reference 2 discloses methods and compositions for improving fetal and child health and development through nutritional supplementation using, for example, sialic acid. Sialic acid, in the form of N-acetylneuraminic acid, is supplied to women before, during, and / or after pregnancy, providing developmental benefits to the nervous system and / or brain of the fetus or child of the woman.

[0005] Human milk oligosaccharides (HMOs) are a group of oligosaccharides that infants cannot digest, and are the third most abundant nutrient in breast milk after lactose and lipids. HMOs promote the growth of beneficial intestinal bacteria, reduce the adhesion of pathogenic bacteria, promote small intestinal maturation, and promote surface glycosylation. Based on the presence or absence of sialic acid residue modification, HMOs can be divided into two main categories: neutral HMOs and acidic HMOs. Neutral HMOs can be further classified according to the presence or absence of fucose residues in their structure into fucosylated HMOs and non-fucosylated HMOs. Neutral HMOs account for more than 70% of the content in breast milk, while fucosylated HMOs account for 35%–50%. The concentration of HMOs in breast milk exhibits dynamic changes during lactation, and fucosylated human milk oligosaccharides show different patterns of change during lactation. 2'-Fucosyllactose is the main fucosylated human milk oligosaccharide, and its concentration gradually decreases with the extension of lactation. Reference 3 discloses a nutritional composition comprising 20%-35% sialylated oligosaccharides and 50%-60% fucosylated neutral oligosaccharides by weight, of which 2'-fucosylated lactose accounts for 25%-35%. This nutritional composition has the effect of helping to improve the gut microbiota and learning and memory abilities of infants fed by older mothers, and can be used to prepare infant formula or probiotic products.

[0006] References:

[0007] Reference 1: CN105106217B;

[0008] Reference 2: CN102946728B;

[0009] Reference 3: CN112841317B. Summary of the Invention

[0010] The problem the invention aims to solve

[0011] Currently, nutritional supplementation during pregnancy, such as folic acid supplementation, is mostly aimed at preventing adverse pregnancy outcomes and abnormal fetal development. For promoting infant growth and development or improving infant physiological characteristics, the usual approach is to directly supplement infant nutrition, such as by consuming fortified formula milk powder.

[0012] However, research on nutrients that can be ingested by the mother, especially from the beginning of pregnancy, to promote infant growth and development or improve infant physiological characteristics remains insufficient. Furthermore, even if a nutrient is considered to provide specific health benefits directly to infants, this does not necessarily mean that it will have the same effect on offspring through mother-to-child transmission when ingested by the mother.

[0013] In this regard, the present invention has discovered that active folic acid substances and nutritional compositions containing active folic acid substances can contribute to the growth of offspring and enhance their antioxidant capacity through maternal-infant transmission. Therefore, the object of the present invention is to provide the non-therapeutic use of active folic acid substances and nutritional compositions containing active folic acid substances, through maternal ingestion, to contribute to the growth of offspring and / or enhance their antioxidant capacity.

[0014] Solution for solving the problem

[0015] To solve the above-mentioned technical problems, the present invention provides the following technical solution:

[0016] [1]. Use of active folic acid compounds in the preparation of foods that, when ingested by the mother during pregnancy and / or lactation, contribute to the growth of offspring and / or to the antioxidant capacity of offspring.

[0017] [2]. Use of a nutritional composition containing active folic acid and N-acetylneuraminic acid in the preparation of foods which, when ingested by the mother during pregnancy and / or lactation, contribute to the growth of offspring and / or to the antioxidant capacity of offspring.

[0018] [3]. According to the use described in [2], wherein in the nutritional composition, the mass ratio of the active folic acid to the N-acetylneuraminic acid is (0.0005 to 0.007):(1 to 5).

[0019] [4]. Use of a nutritional composition containing active folic acid and fucoidan in the preparation of foods which, when ingested by the mother during pregnancy and / or lactation, contribute to the growth of offspring and / or to the antioxidant capacity of offspring.

[0020] [5]. According to the use described in [4], wherein in the nutritional composition, the mass ratio of the active folic acid to the fucoidan is (0.0001 to 0.0015):(0.5 to 5).

[0021] [6]. According to the use described in [4] or [5], wherein the fucoidyl lactose comprises 2'-fucosylation lactose.

[0022] [7]. The use according to any one of [1] to [6], wherein the active folic acid substance comprises at least one of 6S-5-methyltetrahydrofolate, calcium 6S-5-methyltetrahydrofolate and glucosamine 6S-5-methyltetrahydrofolate.

[0023] [8]. The use according to any one of [1] to [7], wherein the contribution to offspring growth includes at least one of the following: contribution to offspring weight gain, contribution to offspring body length gain, contribution to offspring grip strength gain, and contribution to offspring endurance gain.

[0024] [9]. The use according to any one of [1] to [8], wherein the antioxidant effect on offspring includes increasing the SOD content in offspring.

[0025]

[0010] . The use according to any one of [1] to [9], wherein the food helps maintain the brain health of the offspring by inhibiting the radical oxidation of the offspring's body through its antioxidant capacity.

[0026]

[0011] . The use according to any one of [1] to

[0010] is characterized in that the food is infant food, children's food, adolescent food or adult food; the adult food includes at least one of pregnant women's food and postpartum women's food.

[0027] The effects of the invention

[0028] By implementing the above technical solution, the present invention achieves the following technical effects:

[0029] This invention, through extensive research, has discovered that supplementing with active folic acid during pregnancy can promote rapid growth and development in offspring, particularly in muscles and bones. It also enhances the offspring's antioxidant capacity and, to some extent, benefits the offspring's brain and nervous system health. Furthermore, this invention unexpectedly found that supplementing with a combination of active folic acid and N-acetylneuraminic acid, or a combination of active folic acid and fucoidan during pregnancy, can further promote rapid growth and development in offspring, enhance their antioxidant capacity, and benefit their brain health. Moreover, the effects are even more pronounced when active folic acid is combined with N-acetylneuraminic acid or fucoidan in a specific ratio. Detailed Implementation

[0030] The following describes embodiments of the present invention, but the present invention is not limited thereto. Various modifications can be made within the scope of protection claimed in the present invention, and embodiments and examples obtained by appropriately combining the technical means disclosed in different embodiments and examples are also included in the technical scope of the present invention.

[0031] I. Terminology Definition

[0032] In this invention, the range of values ​​represented by “value A to value B”, “value A to value B”, “value A or above” or “value A or below” refers to the range that includes the endpoint values ​​A and B.

[0033] In this invention, the word "may" has two meanings: to perform a certain process and not to perform a certain process.

[0034] In this invention, "optional" or "optionally" means that the event or situation described below may or may not occur, and the description includes both cases in which the event occurs and cases in which the event does not occur.

[0035] In this invention, the terms "a", "an", or "the" may refer to "one", "one or more", "at least one", or "one or more".

[0036] In this invention, the terms "comprising," "having," "including," or "containing" can mean included or open-ended, and do not exclude additional, uncited elements or method steps. At the same time, "comprising," "having," "including," or "containing" can also mean closed-ended, excluding additional, uncited elements or method steps.

[0037] In this invention, the term "about" is used to define that the numerical ranges and parameters of this invention are approximate values, while specific related values ​​have been presented as precisely as possible. Unless otherwise explicitly stated, it should be understood that all ranges, quantities, values, and percentages used in this invention are modified by "about". Here, "about" generally means that the actual value is within ±5%, ±3%, ±1%, or ±0.5% of a specific value or range.

[0038] In this invention, "normal temperature" refers to an indoor ambient temperature of 23±2℃.

[0039] In this invention, "gestation period" and "pregnancy period" can be used interchangeably, referring to the period from fertilization to delivery.

[0040] In this invention, "breastfeeding period" refers to the period from when a mother begins breastfeeding after childbirth until she stops breastfeeding.

[0041] In this invention, "exclusively breastfed" means that the offspring consumes the vast majority (at least 90%, preferably at least 95%, more preferably at least 98%) of its nutrients and / or energy from breast milk.

[0042] In this invention, the term "primarily breastfed" means that the nutrients and / or energy ingested by the offspring are primarily (at least 50%, preferably at least 65%, more preferably at least 75%) derived from breast milk.

[0043] In this invention, "infants and toddlers" refers to the human group under 36 months of age.

[0044] In this invention, "infant" refers to the human group under 12 months of age.

[0045] In this invention, "infant" refers to the human group aged 13 to 36 months.

[0046] In this invention, "children" refers to a group of humans who are older than 3 years and younger than 12 years and are in the growth and development stage.

[0047] In this invention, "adolescent" refers to the group of humans aged 12 years or older and under 18 years old.

[0048] In this invention, "adult" refers to the group of humans aged 18 years or older.

[0049] Unless otherwise defined, other technical and scientific terms used in this invention have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains.

[0050] II. Active folic acid substances

[0051] The active folic acid substances mentioned in this invention refer to 6S-5-methyltetrahydrofolate and its salts.

[0052] The present invention does not particularly limit the source of active folic acid substances. Typically, they can be synthesized by common chemical synthesis methods in the art, such as using folic acid as a raw material, through steps such as reduction, methylation, chiral resolution and optional salt formation.

[0053] In some specific embodiments, the active folic acid substances of the present invention include at least one of 6S-5-methyltetrahydrofolate, calcium 6S-5-methyltetrahydrofolate, and glucosamine 6S-5-methyltetrahydrofolate.

[0054] In some specific embodiments, the active folic acid substance of the present invention is 6S-5-methyltetrahydrofolate, calcium 6S-5-methyltetrahydrofolate, or glucosamine 6S-5-methyltetrahydrofolate.

[0055] In some preferred embodiments, the active folic acid substance of the present invention is calcium 6S-5-methyltetrahydrofolate.

[0056] III. Nutritional compositions containing active folic acid and N-acetylneuraminic acid

[0057] In the nutritional composition containing active folic acid and N-acetylneuraminic acid described in this invention, the active folic acid and N-acetylneuraminic acid are the main active ingredients in the nutritional composition, meaning that the nutritional composition mainly relies on the active folic acid and N-acetylneuraminic acid it contains to exert specific physiological functions. The active folic acid is as described in Part II above.

[0058] The present invention does not specifically limit the source of the N-acetylneuraminic acid. Typically, it can be extracted from natural resources containing sialic acid, such as bird's nest, eggs, and milk; or it can be synthesized by chemical and enzymatic methods, such as condensing N-acetylglucosamine with the potassium salt of di-tert-butyloxosuccinic acid and decarboxylating it under alkaline catalysis to generate N-acetylneuraminic acid, or producing N-acetylmannosamine by catalyzing N-acetylneuraminic acid aldolase; or it can be obtained by fermentation with suitable microorganisms such as Escherichia coli and Bacillus subtilis; or it can be obtained by whole-cell synthesis.

[0059] To achieve better results from maternal intake during pregnancy and / or lactation, which contribute to offspring growth and / or antioxidant activity, in some embodiments, the mass ratio of the active folic acid to the N-acetylneuraminic acid in the nutritional composition containing active folic acid and N-acetylneuraminic acid described in this invention is (0.0005–0.007):(1–5).

[0060] In some preferred embodiments, in the nutritional composition containing active folic acid and N-acetylneuraminic acid described in this invention, the mass ratio of the active folic acid to the N-acetylneuraminic acid is (0.0005–0.007):1, for example, 0.0005:1, 0.0007:1, 0.0009:1, 0.0011:1, 0.0013:1, 0.0015:1, 0.0017:1, 0.0019:1, 0.0021:1, 0.0023:1, 0.0025:1, 0.0027:1, 0.0029:1, 0.0031:1, 0.0033:1, 0.00 35:1, 0.0037:1, 0.0039:1, 0.0041:1, 0.0043:1, 0.0045:1, 0.0047:1, 0.0049:1, 0.0051:1, 0.0053:1, 0.0055:1, 0.0057:1, 0.0059:1, 0.0061:1, 0.0063:1, 0.0065:1, 0.0067:1, or 0.0069:1, etc.; preferably, it can be (0.001~0.007):1; more preferably, it can be (0.003~0.007):1; even more preferably, it can be (0.005~0.007):1.

[0061] In some embodiments, the nutritional composition containing active folic acid and N-acetylneuraminic acid of the present invention is composed of active folic acid and N-acetylneuraminic acid; and in the nutritional composition, the mass ratio of the active folic acid to the N-acetylneuraminic acid is (0.0005-0.007):(1-5).

[0062] The nutritional composition containing active folic acid and N-acetylneuraminic acid described in this invention is usually a synthetic or compounded composition, that is, not a natural composition.

[0063] IV. Nutritional composition containing active folic acid and fucoidan.

[0064] In the nutritional composition containing active folic acid and fucoidan as described in this invention, the active folic acid and fucoidan are the main active ingredients in the nutritional composition, meaning that the nutritional composition mainly relies on the active folic acid and fucoidan it contains to exert specific physiological functions. The active folic acid is as described in Part II above.

[0065] In some embodiments, the fucoidosyllactose of the present invention comprises 2'-fucosyllactose.

[0066] In some specific embodiments, the fucoidosyllactose described in this invention is 2'-fucosyllactose.

[0067] This invention does not specifically limit the source of fucoidosyl lactose. Typically, it can be synthesized by common chemical synthesis methods in the art, such as through glycosylation reactions between lactose acceptors and fucoidosyl donors. It can also be obtained by microbial fermentation, for example, using exogenously added lactose as a substrate and 5'-guanine diphosphate nucleoside-fucose disodium salt formed through the microbial metabolic pathway as a precursor, to synthesize 2'-fucosyl lactose under the action of fucoidosyltransferase.

[0068] In order to obtain better effects of maternal intake during pregnancy and / or lactation on offspring growth and / or antioxidant activity, in some embodiments, in the nutritional composition of the present invention containing active folic acid and fucoidan, the mass ratio of the active folic acid to the fucoidan is (0.0001 to 0.0015):(0.5 to 5).

[0069] In some preferred embodiments, in the nutritional composition containing active folic acid and fucoidan of the present invention, the mass ratio of the active folic acid to the fucoidan is (0.0001–0.0015):1, for example, 0.0001:1, 0.0002:1, 0.0003:1, 0.0004:1, 0.0005:1, 0.0006:1, 0.0 007:1, 0.0008:1, 0.0009:1, 0.0010:1, 0.0011:1, 0.0012:1, 0.0013:1, 0.0014:1, 0.0015:1, etc.; preferably (0.0001~0.0010):1; more preferably (0.0002~0.0009):1; even more preferably (0.0002~0.0005):1.

[0070] In some embodiments, the nutritional composition containing active folic acid and fucoidan of the present invention is composed of active folic acid and fucoidan; and in the nutritional composition, the mass ratio of the active folic acid to the fucoidan is (0.0001 to 0.0015):(0.5 to 5).

[0071] The nutritional composition containing active folic acid and fucoidan described in this invention is usually a synthetic or compounded composition, that is, not a natural composition.

[0072] V. Uses that contribute to offspring growth and / or to offspring's antioxidant capacity.

[0073] This invention proposes that the intake of active folic acid, a combination of active folic acid and N-acetylneuraminic acid, or a combination of active folic acid and fucoidan by pregnant and / or lactating mothers can help their offspring grow and / or enhance their antioxidant capacity. Furthermore, the above effects are even better when active folic acid is combined with N-acetylneuraminic acid or fucoidan in a certain proportion.

[0074] The methods described in this invention that promote offspring growth and antioxidant activity are not intended to treat or prevent diseases.

[0075] Furthermore, this invention provides the use of active folic acid compounds, nutritional compositions containing active folic acid compounds and N-acetylneuraminic acid, and nutritional compositions containing active folic acid compounds and fucoidyl lactose in the preparation of foods that promote the growth of offspring and / or enhance their antioxidant capacity. These foods exert their effects through ingestion by the mother during pregnancy and / or lactation, targeting not only the fetus in the womb and breastfed infants but also extending into childhood and exerting a sustained effect on the offspring. Therefore, the offspring referred to in this invention include fetal offspring and / or infant offspring, and optionally, children.

[0076] The infants described in this invention can be breastfed. In some embodiments, the infants described in this invention are exclusively or primarily breastfed. Furthermore, the active folic acid substances, nutritional compositions containing active folic acid substances and N-acetylneuraminic acid, nutritional compositions containing active folic acid substances and fucoidyl lactose, and foods containing active folic acid substances or their nutritional compositions, through maternal-infant transmission, exert their effects on promoting offspring growth and / or enhancing the offspring's antioxidant capacity via the mother-to-child transmission route.

[0077] In some embodiments, the contribution to offspring growth includes at least one of contributing to offspring weight gain, contributing to offspring body length gain, contributing to offspring grip strength gain, and contributing to offspring endurance gain.

[0078] In some implementations, the contribution to offspring growth includes contributing to increased offspring weight, increased offspring body length, increased offspring grip strength, and increased offspring endurance.

[0079] In some implementations, the contribution to offspring growth is to contribute to increased offspring weight, increased offspring body length, increased offspring grip strength, or increased offspring endurance.

[0080] In some implementations, the benefit of the offspring's antioxidant capacity includes increasing the SOD content in the offspring.

[0081] In some implementations, the benefit of the offspring's antioxidant capacity includes increasing the SOD content in the offspring's serum.

[0082] Oxidative stress is known to result from an imbalance in the ratio of pro-oxidants to antioxidants within cells. Free radicals, non-free radical reactive oxygen species (ROS), and reactive nitrogen species (RNS) are collectively referred to as oxidants, which readily lead to free radical chain reactions. Antioxidants, including, for example, superoxide dismutase (SOD), catalase, vitamin C, vitamin E, and carotenoids, can neutralize excess free radicals and protect cells from the harmful effects of oxidants (Panfoli I, Candiano G, Malova M, De Angelis L, Cardiello V, Buonocore G, Ramenghi LA. Oxidative Stress as a Primary Risk Factor for Brain Damage in Preterm Newborns. Front Pediatr. 2018 Nov 29; 6:369.). Studies have shown that oxidative stress is considered a major factor in the pathogenesis of many cardiovascular and neurological diseases, malignant tumors, diabetes, aging, and inflammation (Rahal A, Kumar A, Singh V, Yadav B, Tiwari R, Chakraborty S, Dhama K. Oxidative stress, prooxidants, and antioxidants: the interplay. Biomed Res Int. 2014; 2014:761264.. Lugrin J, Rosenblatt-Velin N, Parapanov R, Liaudet L. The role of oxidative stress during inflammatory processes. Biol Chem. 2014 Feb; 395(2):203-30.). Meanwhile, studies have shown that oxidative stress is involved in the pathogenesis of early developmental brain injury caused by hyperoxia, hypoxia-ischemia, drugs, and mechanical damage. Oxidative stress is one of the factors that cause brain damage during brain development and neurodevelopment (Ikonomidou C, Kaindl AM. Neuronal death and oxidative stress in the developing brain. Antioxid Redox Signal. 2011 Apr 15; 14(8):1535-50.).

[0083] However, this invention has found that when pregnant and / or lactating mothers consume active folic acid substances, combinations of active folic acid substances and N-acetylneuraminic acid, or combinations of active folic acid substances and fucose-based lactose, the levels of the antioxidant SOD in their offspring can be increased, further enhancing the body's antioxidant capacity. Therefore, this invention suggests that when pregnant and / or lactating mothers consume active folic acid substances, combinations of active folic acid substances and N-acetylneuraminic acid, combinations of active folic acid substances and fucose-based lactose, or foods containing the above substances or combinations, it can, to a certain extent, benefit the maintenance of the brain and nervous system health of their offspring, and may even alleviate or address brain damage caused by oxidative stress. The methods described in this invention for maintaining the health of the offspring's brain and nervous system are not intended to treat or prevent disease.

[0084] In some implementations, the food described in this invention is infant food, children's food, adolescent food, or adult food.

[0085] In some preferred embodiments, the food of the present invention is a food for pregnant women or a food for postpartum women. The food for pregnant women is suitable for consumption by pregnant women, and the food for postpartum women is suitable for consumption by postpartum women, especially breastfeeding women.

[0086] In some embodiments, the food is candy, beverage, or dairy product; the candy includes jelly candy, compressed candy, etc.; the beverage includes tea beverages, coffee beverages, fruit-flavored beverages, etc.; the dairy product includes milk powder, cheese, yogurt, liquid milk, etc.

[0087] In some implementations, the food is a health food, such as various types of oral preparations; for example, the oral preparations may be tablets, pills, granules, powders, capsules, and oral liquids, etc.

[0088] This invention does not impose any specific absolute limits on the content of the active folic acid substances, N-acetylneuraminic acid, and fucose-based lactose in food, as long as they meet the requirements of local food-related laws and regulations.

[0089] Depending on the type of food and the end needs of the target audience, in some embodiments, the food may also contain one or more of the following ingredients: plant-based ingredients, animal dairy ingredients, animal meat ingredients, functional additives, and any acceptable excipients.

[0090] Examples of plant-based ingredients include fruits such as figs, pomegranates, kiwis, oranges, tangerines, pineapples, strawberries, apples, bananas, grapes, pears, cherries, blueberries, blackberries, blackcurrants, cranberries, raspberries, melons, amla, and bilberries, or their extracts; fruits and vegetables such as onions, cucumbers, tomatoes, cauliflower, carrots, spinach, kale, Brussels sprouts, garlic, basil, and oregano, or their extracts; grains such as rice (indica, japonica, glutinous rice), cereals (wheat, barley, oats, rye), corn, sorghum, millet, sorghum, yellow millet, buckwheat, soybeans, broad beans, peas, mung beans, red beans, and kidney beans, or their extracts; nuts such as walnuts, pistachios, cashews, hazelnuts, almonds, apricot kernels, pine nuts, peanuts, sunflower seeds, chestnuts, macadamia nuts, and ginkgo nuts, or their extracts; coffee or its extracts; and some medicinal and edible herbal medicines or their extracts.

[0091] Animal dairy product ingredients can include fresh milk from cows and sheep, as well as reprocessed dairy products such as whole milk powder, skim milk powder, whey protein concentrate, desalted whey powder, whey protein powder, hydrolyzed whey protein powder, and casein powder.

[0092] Examples of animal meat product ingredients include pork, beef, mutton, seafood, and poultry.

[0093] Examples of functional additives include vitamin supplements, mineral supplements, nucleotide supplements, dietary fiber, and functional polyunsaturated fatty acid supplements.

[0094] Any acceptable excipients may include solvents, antioxidants, antibacterial agents, thickeners, diluents, cosolvents, stabilizers, emulsifiers, fillers, disintegrants, lubricants, coating materials, anti-caking agents, flavoring agents, sweeteners, food flavorings, and food colorings.

[0095] Example

[0096] The embodiments of the present invention will be described in detail below with reference to examples. However, those skilled in the art will understand that the following examples are for illustrative purposes only and should not be considered as limiting the scope of the invention. Unless otherwise specified, specific conditions in the examples are performed under conventional conditions or conditions recommended by the manufacturer. Unless otherwise specified, all materials and instruments used are conventional products that can be commercially available.

[0097] 1. Testing materials

[0098] 1.1. Laboratory animals and grouping

[0099] Select 120 8-week-old sexually mature SPF female rats and 120 SPF male rats; purchased from Hangzhou Medical College, with the animal certificate number 20240318Aazz0100000836 and the production license number: SCXK(Zhe)2024-002. Feeding conditions: The animals are raised in a barrier environment, with the indoor temperature at 25±1°C and the humidity at 45±5%. The animals have free access to drinking water, and are raised in a 12h light-dark alternating environment daily. This experiment has passed the animal experiment ethics review of Southeast University; ethics number: 20240316003.

[0100] After 3 days of adaptive feeding of the animals, female and male rats were caged together at a ratio of 1:1. The starting point of gavage intervention was when the female mouse showed a vaginal plug. The female mouse was continuously gavaged until the offspring mice were weaned and then stopped; in the experimental group, the corresponding dose of the sample aqueous solution was given according to the animal grouping, and the control group was given the corresponding dose of normal saline. Gavage was performed once a day for 6 consecutive weeks, and maintenance feed was given to each dose group. The low and high doses of active folic acid were 5.3 and 10.1 (μg / d / rat), the low and high doses of N-acetylneuraminic acid were 1.5 and 7.5 (mg / d / rat), and the low and high doses of 2'-fucosyllactose were 12.6 and 37.8 (mg / d / rat). The specific doses of each group are shown in Table 1 below. During the gavage process, the body weight of the female mouse, the body length and body weight data of the offspring mice were monitored weekly.

[0101] Table 1 Gavage doses of experimental animals

[0102] 1.2. Instruments, consumables and reagents

[0103] The consumables, reagents and experimental instruments used in the experiment are shown in Tables 2 and 3.

[0104] Table 2 Main experimental consumables and reagents

[0105] Table 3 Main experimental instruments

[0106] 2. Detection methods

[0107] 2.1. Monitoring and recording of the body weight and body length of female and offspring mice

[0108] (1) Recording of the female mouse's body weight: Record the changes in the female mouse's body weight at the time of enrollment (0 week), 1 week, 2 weeks, 0 week after delivery, 1 week after delivery, 2 weeks after delivery, and 3 weeks after delivery respectively.

[0109] (2) Recording of the offspring mouse's body weight: Record the changes in the offspring mouse's body weight at 0 week, 1 week, 2 weeks, and 3 weeks after birth respectively.

[0110] (3) Recording of the offspring mouse's body length: Record the changes in the offspring mouse's body length at 0 week, 1 week, 2 weeks, and 3 weeks after birth respectively.

[0111] 2.2. Roller Test (Roller Fatigue Test)

[0112] The rotarod fatigue test for baby mice consisted of a learning period and a testing period to evaluate the effects of the sample on the coordination and fatigue endurance of the baby mice. Baby mice were placed on the rotarod fatigue apparatus daily for 1-4 days after weaning for learning, and tested on the 5th day. During the learning period, the rotarod speed was set to 20 r / min for 10 minutes. After the learning period, the testing experiment was conducted at a speed of 40 r / min. The time it took for the baby mice to fall, i.e., the roller latency (s), was recorded. The experiment was repeated three times, and the average value was calculated.

[0113] 2.3. Grip strength test of baby rats

[0114] Before testing, the offspring mice were placed in the testing laboratory for 1.5 hours to acclimatize. The offspring mice were then gently removed from their cages, their tails gently grasped, allowing them to grip the digital force gauge, while the tail was gently pulled away parallel to the ground. When maximum force was applied to the offspring mice, the force gauge readings were recorded. The measurements were repeated three times, and the peak grip force (N), peak time (s), and grip duration (s) were calculated to assess the offspring mice's muscle development.

[0115] 2.4. Serum collection and indicator detection of female and offspring mice

[0116] After the experiment, the mother mice were anesthetized by intraperitoneal injection of 5% sodium pentobarbital solution. Blood was collected from the abdominal aorta, centrifuged at 3000 rpm for 5 minutes, and the serum was separated and stored at -80℃. After weaning, one offspring from each mother was selected and anesthetized by intraperitoneal injection of 5% sodium pentobarbital solution. Two blood samples were collected from the abdominal aorta. One sample was placed in an anticoagulant tube (to be sent for testing on the same day), and the other was placed in a procoagulant tube. The samples were centrifuged at 3000 rpm for 5 minutes, the serum was separated, and stored at -80℃.

[0117] (1) Detection of serum glucose (Glu) in female mice: After collecting serum from female mice, the serum glucose level in female mice was detected by glucose oxidase method using a fully automated biochemical analyzer.

[0118] (2) Detection of glycosylated albumin (GA) in maternal mouse serum: The GA content in maternal mouse serum was detected using a fully automated microplate reader with reference to the GA enzyme-linked immunosorbent assay (ELISA) method.

[0119] (3) Detection of FA in maternal serum: The FA content in maternal serum was detected using a fully automated ELISA reader with reference to the FA enzyme-linked immunosorbent assay (ELISA) method.

[0120] (4) Detection of folic acid (FA) in the serum of offspring mice: The FA content in the serum of offspring mice was detected using a fully automated microplate reader with reference to the FA enzyme-linked immunosorbent assay (ELISA) method.

[0121] (5) Detection of superoxide dismutase (SOD) in the blood of offspring mice: The SOD content in the serum of offspring mice was detected using an automated microplate reader with reference to the SOD enzyme-linked immunosorbent assay (ELISA) method.

[0122] 3. Test Results

[0123] 3.1. Weight growth indicators of female and offspring mice

[0124] Table 4. Weight results of female mice (g)

[0125] Before intervention, there was no significant difference in the weight of the mother mice in different samples, as shown in Table 4. Compared with the control group, there was no significant difference in the weight changes of the mother mice in Examples 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, and 11 during pregnancy and 2 weeks postpartum; however, at 3 weeks postpartum, the weight of the mother mice in Example 1 was significantly lower than that in the control group, indicating that the low-dose active folic acid group had a certain promoting effect on the postpartum weight recovery of the mother mice.

[0126] Table 5. Weight results of offspring mice (g)

[0127] Weight is an important indicator of healthy growth and development in infants and young children. Table 5 shows that after continuous intervention, the birth weight of most offspring mice in Examples 2, 5, 6, 7, 10, and 11 was significantly higher than that of the control group. With continued breastfeeding, at 1 week after birth, the birth weight of offspring mice in Examples 2, 4, 6, 7, 8, 9, 10, and 11 was significantly higher than that of the control group; at 2 weeks after birth, the birth weight of offspring mice in Examples 2, 4, 6, 7, 8, 9, 10, and 11 was significantly higher than that of the control group; and at 3 weeks after birth, the birth weight of offspring mice in Examples 4, 6, 7, 8, 10, and 11 was significantly higher than that of the control group.

[0128] The above experimental results show that, compared with the control group, the high-dose group of active folic acid can promote rapid weight gain in offspring mice after birth; the high-dose group of N-acetylneuraminic acid showed a significant trend of promoting weight gain in offspring mice starting from 2 weeks after birth; and the high-dose group of 2'-fucosylated lactose can promote rapid weight gain in offspring mice after birth.

[0129] Furthermore, this invention unexpectedly discovered that intervention with a mixture of high-dose active folic acid and low-dose N-acetylneuraminic acid significantly promoted weight gain in offspring starting two weeks after birth, and this effect was superior to that of a single substance, showing a synergistic effect. Intervention with a high-dose active folic acid and a combination of low and high doses of 2'-fucosylated lactose significantly promoted rapid weight gain in offspring after birth, and the 2'-fucosylated lactose dose group showed a dose-dependent trend.

[0130] Table 6. Results of mouse body length (cm)

[0131] Height measurements during infancy are important indicators for assessing healthy growth and development. Table 6 shows that after continuous intervention, compared with the control group, the body length of offspring mice in different examples showed different differences at birth. Among them, the body length of offspring mice in examples 5, 7, 10, and 11 was significantly higher than that of the control group, while there was no significant difference between the other examples and the control group. One week after birth, the body length of offspring mice in examples 4, 5, 6, 7, 10, and 11 was significantly higher than that of the control group. Two weeks after birth, the body length of offspring mice in examples 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, and 11 was significantly higher than that of the control group. Three weeks after birth, the body length of offspring mice in examples 2, 3, 4, 5, 6, 8, 9, and 11 was significantly higher than that of the control group.

[0132] The above experimental results show that, compared with the control group, the high-dose active folic acid group can promote the rapid growth of the body length of the offspring after 2 weeks of age; the low- and high-dose N-acetylneuraminic acid groups show a significant trend of promoting the increase of the body length of the offspring from 1 to 2 weeks after birth; and 2'-fucosylated lactose can promote the rapid growth of the body length of the offspring after birth.

[0133] Furthermore, this invention unexpectedly discovered that intervention with a mixture of high-dose active folic acid and high-dose N-acetylneuraminic acid significantly promoted rapid growth in the length of offspring starting two weeks after birth; intervention with a combination of high-dose active folic acid and low-to-high-dose 2'-fucosylated lactose significantly promoted rapid growth in the length of offspring after birth.

[0134] 3.2. Roller Test (Roller Fatigue Test)

[0135] Table 7. Latency period (s) of baby mice rolling on a roller.

[0136] A longer rolling latency in offspring indicates stronger coordinated grasping ability. Table 7 shows that, compared with the control group, the rolling latency of offspring in Examples 3, 4, 5, 6, 7, 8, 9, 10, and 11 was increased to varying degrees, with Examples 6 and 7 showing the greatest increase. The results indicate that, compared with the blank control group, there was no significant increase in rolling latency in the groups receiving different doses of active folic acid alone, while the rolling latency of offspring receiving different doses of N-acetylneuraminic acid alone and different doses of 2'-fucosylated lactose alone were increased to varying degrees. Furthermore, this invention unexpectedly discovered that the combination of low-dose N-acetylneuraminic acid and high-dose active folic acid showed better performance after gavage than the gavage alone group, and the effect was better than that of high-dose N-acetylneuraminic acid plus high-dose active folic acid. The combination of low- and high-dose active folic acid plus low-dose 2'-fucosylated lactose increased the rolling latency of offspring mice significantly after gavage, indicating that it has a certain effect on promoting the coordinated grasping ability of offspring mice.

[0137] Table 8 Results of the grip strength test on rats

[0138] A higher peak grip strength indicates stronger grasping ability and muscle strength in the offspring mice; a longer peak time and grip duration indicate greater endurance. Table 8 shows that compared with the control group, the peak grip strength of offspring mice in Examples 3, 4, 5, 6, and 9 was significantly higher; the peak time of offspring mice in Examples 1, 5, 6, and 8 was significantly higher than that of the control group; and the grip duration of offspring mice in Examples 1, 3, 5, 6, and 9 was significantly higher than that of the control group. The results showed that low-dose active folic acid intervention significantly increased the peak grasping time and grasping duration in offspring, thus promoting grip strength and endurance. Low-dose N-acetylneuraminic acid significantly increased the peak grasping force and grasping duration in offspring. Different doses of 2'-fucosylated lactose all increased the peak grasping force, peak time, and grasping duration in offspring, indicating a positive promoting effect on grip strength and endurance development. Furthermore, intervention with a combination of low-dose active folic acid and low-dose 2'-fucosylated lactose significantly increased the peak grasping force and grasping duration in offspring, thus promoting grip strength and endurance.

[0139] 3.3. Results of blood parameters in female mice

[0140] Table 9. Serum Glu Detection Results (mmol / L) in Maternal Rats

[0141] Abnormal blood glucose levels during pregnancy have adverse effects on both the mother and the fetus. Table 9 shows the results of blood glucose testing in the mother mice after the intervention. The results indicate that, compared with the control group, the blood glucose levels in the mother mice in Examples 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, and 11 all decreased to some extent, with no significant difference among the groups (P > 0.05).

[0142] Table 10. Serum GA detection results (mmol / L) in female mice

[0143] Serum glycated albumin (GA) is an indicator of average blood glucose levels over the past 2-3 weeks. Table 10 shows the GA test results in maternal mice. The results indicate that, compared with the control group, there were no significant differences in serum GA levels and GA% in Examples 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, and 11 (P > 0.05). The results suggest that, within the intervention period, different doses of active folic acid, N-acetylneuraminic acid, and 2'-fucosylated lactose, as well as their combinations, did not increase the risk of gestational hyperglycemia and had no significant effect on gestational blood glucose levels.

[0144] Table 11. Results of serum FA detection in female mice (μg / L)

[0145] After the intervention, the serum folic acid levels in the mother mice were shown in Table 11. Compared with the control group, the serum folic acid levels in mother mice in Examples 2, 3, 4, 5, 6, 7, 8, 9, 10, and 11 all showed varying degrees of increase, but the differences were not statistically significant (P > 0.05). The supplementation of folic acid and the combination did not lead to a significant increase in serum folic acid levels in the mother mice. This may be because folic acid is absorbed and metabolized in the body and secreted through breast milk, thus consuming the supplemented folic acid. The folic acid levels in the blood of the other groups were not significantly different from the control group, because the mother mice obtained some folic acid supplementation through their basal diet.

[0146] 3.4. Results of Blood Indicators Tests in Offspring Mice

[0147] Table 12. Serum FA detection results of offspring mice (μg / L)

[0148] During the experiment, the offspring mice mainly obtained folic acid through their milk. The serum folic acid levels in the offspring mice are shown in Table 12: Compared with the control group, the serum folic acid levels in offspring mice from Examples 1, 2, 7, and 11 were significantly increased (P < 0.05). The results indicate that intervention with different doses of active folic acid promoted an increase in serum folic acid levels in offspring mice, exhibiting a dose-dependent effect. Furthermore, the high-dose active folic acid plus low-dose N-acetylneuraminic acid group significantly increased serum folic acid levels in offspring mice, and the high-dose active folic acid plus high-dose 2'-fucosylated lactose group significantly increased serum folic acid levels, exceeding the levels in the respective monomeric intervention groups.

[0149] Table 13. SOD detection results in the serum of offspring mice (U / mL)

[0150] A higher superoxide dismutase (SOD) value indicates a higher antioxidant capacity of the body. Table 13 shows the SOD test results of mouse offspring serum. The results indicate that, compared with the control group, the SOD values ​​of offspring serum from Examples 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, and 11 were significantly increased; among them, the SOD values ​​of offspring serum from Examples 8 and 11 were higher than those from Examples 2, 4, and 6.

[0151] The above experimental results show that, compared with the blank control group, the different doses of active folic acid, different doses of N-acetylneuraminic acid, and 2'-fucosylated lactose administered by gavage all significantly increased the serum SOD value of offspring mice, and all showed an increasing trend in effect with increasing dosage. Furthermore, this invention unexpectedly discovered that the serum SOD value of offspring mice after gavage administration of the combination of active folic acid and N-acetylneuraminic acid was higher than that after gavage administration alone, and the combination of high-dose active folic acid and high-dose N-acetylneuraminic acid significantly improved the antioxidant capacity of offspring mice; the serum SOD value of offspring mice after gavage administration of the combination of active folic acid and 2'-fucosylated lactose was higher than that after gavage administration alone, and the combination of high-dose active folic acid and high-dose 2'-fucosylated lactose significantly improved the antioxidant capacity of offspring mice.

Claims

1. Use of active folic acid compounds in the preparation of foods that, when ingested by the mother during pregnancy and / or lactation, contribute to the growth of offspring and / or to the antioxidant capacity of offspring.

2. The use of a nutritional composition containing active folic acid and N-acetylneuraminic acid in the preparation of foods that, when ingested by the mother during pregnancy and / or lactation, contribute to the growth of offspring and / or to the antioxidant capacity of offspring.

3. The use according to claim 2, characterized in that, In the nutritional composition, the mass ratio of the active folic acid to the N-acetylneuraminic acid is (0.0005-0.007):(1-5).

4. The use of a nutritional composition containing active folic acid and fucoidan in the preparation of foods that, when ingested by the mother during pregnancy and / or lactation, contribute to the growth of offspring and / or to the antioxidant capacity of offspring.

5. The use according to claim 4, characterized in that, In the nutritional composition, the mass ratio of the active folic acid to the fucoidan is (0.0001–0.0015):(0.5–5).

6. The use according to claim 4 or 5, characterized in that, The fucoidyl lactose includes 2'-fucosylation lactose.

7. The use according to any one of claims 1 to 6, characterized in that, The active folic acid compounds include at least one of 6S-5-methyltetrahydrofolate, calcium 6S-5-methyltetrahydrofolate, and glucosamine 6S-5-methyltetrahydrofolate.

8. The use according to any one of claims 1 to 7, characterized in that, The benefits to offspring growth include at least one of the following: benefits to offspring weight gain, benefits to offspring body length gain, benefits to offspring grip strength gain, and benefits to offspring endurance gain.

9. The use according to any one of claims 1 to 8, characterized in that, The benefits to offspring's antioxidant capacity include increasing the SOD content in offspring.

10. The use according to any one of claims 1 to 9, characterized in that, The food helps maintain the brain health of offspring by inhibiting oxidative stress in offspring and thus helping to maintain the offspring's antioxidant capacity.

11. The use according to any one of claims 1 to 10, characterized in that, The food is infant food, children's food, adolescent food, or adult food; the adult food includes at least one of pregnant women's food and postpartum women's food.

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