Active folic acid substance and application of nutritional composition containing active folic acid substance

Abstract

The invention belongs to the field of food, and particularly relates to an active folic acid substance and application of a nutritional composition containing the active folic acid substance. Specifically, the invention provides a method. The invention provides an active folic acid substance. The invention relates to a nutritional composition containing active folic acid substances and N-acetylneuraminic acid and application of the nutritional composition containing the active folic acid substances and fucosyllactose to preparation of food which is beneficial to growth of offspring organisms and / or oxidation resistance of the offspring organisms after being ingested by mothers in the gestation period and / or the lactation period. The invention further discloses application of the nutritional composition containing the active folic acid substances and the N-acetylneuraminic acid and the nutritional composition containing the active folic acid substances and the fucosyllactose. It is found that the active folic acid substances supplemented in the gestation period or the combination of the active folic acid substances and N-acetylneuraminic acid or fucosyllactose can promote rapid growth and development of offspring organisms, especially can promote rapid growth and development of offspring muscles and bones, can also improve the oxidation resistance of the offspring organisms, and can improve the immunity of the offspring organisms. And the health of the brain and nervous system of the offspring can be maintained to a certain extent.

Description

Technical Field

[0001] The present invention belongs to the field of food, and specifically relates to the use of active folic acid substances and nutritional compositions containing active folic acid substances, and more specifically relates to the use of active folic acid substances and nutritional compositions containing active folic acid substances, which are ingested by mothers to help the growth of offspring and / or help the offspring's body resist oxidation. Background Art

[0002] Nutrition in the early stages of life plays an irreplaceable role in the health of the entire life process. Reasonable nutritional intake by the mother not only determines the quality of embryonic development, but also has a profound impact on the growth and development of the offspring. Nutrition in the early stages of life has an important impact on fertilized egg implantation, cell differentiation, embryonic development, pregnancy outcomes, child growth, intellectual development, learning ability, and disease resistance. Nutrition in the early stages of life directly determines the physical growth of children, and birth weight is often used as an indicator of intrauterine nutritional status. Malnutrition in infancy and childhood may lead to irreversible growth retardation, disease, and even death in children.

[0003] Folic acid is a B vitamin that the human body cannot synthesize on its own and must be obtained through additional intake. As an important cofactor in one-carbon unit metabolism, folic acid mediates the de novo synthesis of purine and thymidine in the body and regenerates homocysteine ​​(Hcy) into methionine, thereby supporting a wide range of methylation reactions in the body, including DNA, protein, neurotransmitters, etc. Folic acid deficiency can lead to impaired DNA synthesis and affect cell division and reproduction. Low folate levels during pregnancy are associated with multiple defects in offspring, such as neonatal respiratory distress syndrome (NRDS), congenital heart defects, growth retardation, and low birth weight. Folic acid and its metabolic-related B vitamins during pregnancy are very important for offspring brain development and function. Reference 1 discloses a nutritional supplement for pregnant women, comprising L-methylfolate or L-methylfolate, arginine and vitamin B12; wherein L-methylfolate avoids the problem of inability to absorb and convert folic acid due to genetic defects, and avoids the adverse reactions caused by folic acid accumulation in the body when pregnant women cannot absorb and convert folic acid; arginine can promote blood circulation and can effectively meet the needs of pregnant women for more semi-essential amino acids during pregnancy; avoid the occurrence of common diseases in pregnant women such as pregnancy-induced hypertension, eclampsia, and pregnancy-induced depression; and at the same time, the combination of L-methylfolate and arginine has good fusion.

[0004] N-acetylneuraminic acid, also known as sialic acid, is an acetylated derivative of acidic sugar neuraminic acid. Sialic acid is present in high levels in the brain, milk, blood and neural tissue mucin of mammals, with the highest content in the brain, and is an important structural and functional component of gangliosides. Studies have shown that due to the large difference in sialic acid content and structure between cow's milk and breast milk, breast-fed infants have higher overall scores in cognitive development than infants fed with infant formula, and N-acetylneuraminic acid in breast milk is of great significance for promoting the development of the nervous system of infants and enhancing immunity. Reference 2 discloses a method and composition for improving the health and development of fetuses and children by using, for example, sialic acid for nutritional supplementation, wherein sialic acid is provided to women before, during and / or after pregnancy in the form of N-acetylneuraminic acid, and the sialic acid provides developmental benefits to the nervous system and / or brain of the fetus or child of the woman.

[0005] Human milk oligosaccharides (HMO) are a group of oligosaccharides that infants cannot digest. They are the third largest nutrient in breast milk after lactose and lipids. HMO has the functions of promoting the growth of beneficial intestinal bacteria, reducing the adhesion of intestinal pathogens, promoting small intestinal maturation and surface glycosylation. According to the presence or absence of sialic acid residue modification, HMO can be divided into two categories: neutral human milk oligosaccharides and acidic human milk oligosaccharides. Among them, neutral human milk oligosaccharides can be divided into fucosylated human milk oligosaccharides and non-fucosylated human milk oligosaccharides according to whether there are fucose residues in the structure. The content of neutral human milk oligosaccharides in breast milk accounts for more than 70%, and the content of fucosylated human milk oligosaccharides in breast milk is 35% to 50%. The HMO concentration in breast milk shows dynamic changes during lactation, and fucosylated breast milk oligosaccharides show different change patterns during lactation. 2'-fucosyllactose is the main fucosylated breast milk oligosaccharide, and its concentration shows a gradual downward trend with the extension of the lactation period. Reference document 3 discloses a nutritional composition, which contains 20%-35% sialylated oligosaccharides and 50%-60% fucosylated neutral oligosaccharides by weight, of which 2'-fucosyllactose accounts for 25%-35%. The nutritional composition has the function of assisting in improving the intestinal microecology and learning and memory ability of infants fed by older mothers, and can be used to prepare infant formula milk powder or probiotic products.

[0006] References:

[0007] Reference 1: CN105106217B;

[0008] Reference 2: CN102946728B;

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

[0010] Problem that the invention aims to solve

[0011] At present, nutritional supplements during pregnancy, such as supplementing folic acid, are mostly used to avoid adverse pregnancy and abnormal fetal development. In terms of promoting the growth and development of infants or improving their physiological characteristics, the current common choice is to directly supplement infants with nutrients, such as feeding infants with formula milk with added nutrients.

[0012] However, research on nutrients that can be ingested by the mother, especially from the beginning of pregnancy, to promote infant growth or improve the physiological characteristics of infants is still insufficient. Moreover, even if nutrients are considered to be directly given to infants to exert specific health benefits, it does not mean that they can play the same role on offspring through the mother-to-child transmission pathway when ingested by the mother.

[0013] In this regard, the present invention has found that active folic acid substances and nutritional compositions containing active folic acid substances can contribute to the growth of offspring through mother-to-child transmission and help improve the antioxidant capacity of offspring. Therefore, the purpose of the present invention is to provide non-therapeutic uses of active folic acid substances and nutritional compositions containing active folic acid substances that contribute to the growth of offspring and / or the antioxidant capacity of offspring through mothers' ingestion.

[0014] Solutions for solving problems

[0015] In order to solve the above technical problems, the present invention provides the following technical solutions:

[0016] [1] Use of active folic acid in the preparation of food that is ingested by mothers during pregnancy and / or lactation to help the growth of offspring and / or to help the offspring's body resist oxidation.

[0017] [2] Use of a nutritional composition containing active folic acid substances and N-acetylneuraminic acid in the preparation of a food that is ingested by mothers during pregnancy and / or lactation and that helps the offspring's body growth and / or helps the offspring's body anti-oxidation.

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

[0019] [4] Use of a nutritional composition containing active folic acid and fucosyllactose in the preparation of a food that is ingested by mothers during pregnancy and / or lactation and that helps the growth of offspring and / or helps the offspring's body resist oxidation.

[0020] [5]. The use according to [4], wherein in the nutritional composition, the mass ratio of the active folic acid substance to the fucosyllactose is (0.0001-0.0015):(0.5-5).

[0021] [6]. The use according to [4] or [5], wherein the fucosyllactose includes 2'-fucosyllactose.

[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, 6S-5-methyltetrahydrofolate calcium and 6S-5-methyltetrahydrofolate glucosamine salt.

[0023] [8]. The use according to any one of [1] to [7], wherein the helping the offspring's body growth includes at least one of helping the offspring to increase weight, helping the offspring to increase body length, helping the offspring to increase grip strength, and helping the offspring to increase endurance.

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

[0025]

[10] . The use according to any one of [1] to [9], wherein the food helps maintain the brain health of the offspring by helping the offspring's body resist oxidation and inhibiting the offspring's body's oxidative stress.

[0026]

[11] . The use according to any one of [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 woman food and postpartum woman food.

[0027] Effects of the Invention

[0028] Through the implementation of the above technical solution, the present invention achieves the following technical effects:

[0029] The present invention has found through a large number of studies that supplementing active folic acid substances during pregnancy can promote the rapid growth and development of the offspring body, especially the rapid growth and development of the offspring's muscles and bones, and can also improve the antioxidant capacity of the offspring body, and is beneficial to the brain and nervous system health of the offspring to a certain extent. Further, the present invention unexpectedly found that the combination of supplementing active folic acid substances and N-acetylneuraminic acid during pregnancy, or the combination of supplementing active folic acid substances and fucosyllactose, can promote the rapid growth and development of the offspring body, and improve the antioxidant capacity of the offspring body, and provide benefits to the brain health of the offspring. In addition, when active folic acid substances are combined with N-acetylneuraminic acid or fucosyllactose in a certain proportion, the above effect is better. DETAILED DESCRIPTION

[0030] The following describes the embodiments of the present invention, but the present invention is not limited thereto. Various changes can be made within the scope of the present invention, and the 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. Definition of Terms

[0032] In the present invention, a numerical range expressed using “a value A to a value B”, “a value A - a value B”, “above a value A” or below a value A means a range including the endpoints A and B.

[0033] In the present invention, the word "may" includes both performing a certain process and not performing a certain process.

[0034] In the present invention, "optional" or "optionally" means that the subsequently described event or circumstance may or may not occur, and the description includes instances where the event occurs and instances where it does not occur.

[0035] In the present invention, the term "a" or "an" or "the" may mean "one", and may also mean "one or more", "at least one" and "one or more than one".

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

[0037] 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 ±5%, ±3%, ±1% or ±0.5% of a particular value or range.

[0038] In the present invention, "normal temperature" refers to an indoor ambient temperature of 23±2°C.

[0039] In the present invention, "gestation period" and "pregnancy period" are used interchangeably and refer to the period from fertilization to birth.

[0040] In the present invention, the "breastfeeding period" refers to the period from the start of breastfeeding to the cessation of breastfeeding after a mother gives birth.

[0041] In the present invention, "exclusively breastfed" means that most (at least 90%, preferably at least 95%, more preferably at least 98%) of the nutrients and / or energy consumed by the offspring comes from breast milk.

[0042] In the present invention, the term "primarily fed with breast milk" means that the nutrients and / or energy intake of the offspring mainly (at least 50%, preferably at least 65%, more preferably at least 75%) comes from breast milk.

[0043] In the present invention, "infants" refers to a human group under 36 months of age.

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

[0045] In the present invention, "infants" refers to a human group of 13 to 36 months old.

[0046] In the present invention, "children" refers to a human group that is older than 3 years old and younger than 12 years old and is in the growth and development stage.

[0047] In the present invention, "teenagers" refers to a human group aged 12 years or older and younger than 18 years old.

[0048] In the present invention, "adult" refers to a human group of people aged 18 years or older.

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

[0050] II. Active folic acid substances

[0051] The active folic acid substance described in the present invention refers to 6S-5-methyltetrahydrofolate and its salt.

[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 reduction, methylation, chiral resolution and optional salt formation steps.

[0053] In some specific embodiments, the active folic acid substance described in the present invention includes at least one of 6S-5-methyltetrahydrofolate, 6S-5-methyltetrahydrofolate calcium and 6S-5-methyltetrahydrofolate glucosamine salt.

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

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

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

[0057] In the nutritional composition containing active folic acid and N-acetylneuraminic acid of the present invention, the active folic acid and N-acetylneuraminic acid are the main effective ingredients in the nutritional composition, that is, the nutritional composition mainly relies on the active folic acid and N-acetylneuraminic acid contained therein to exert specific physiologically active functions. The active folic acid is as described in the above-mentioned Part II.

[0058] The present invention does not particularly limit the source of the N-acetylneuraminic acid. Typically, it can be extracted from natural resources containing sialic acid, such as bird's nests, eggs, milk, etc.; or, it can be synthesized by chemical and enzymatic methods, such as condensing N-acetylglucosamine with potassium salt of di-tert-butyloxysuccinic acid, and decarboxylating it under the catalysis of alkali 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] In order to obtain better intake by mothers during pregnancy and / or lactation to help the growth of offspring and / or the antioxidant effect of offspring, in some embodiments, in the nutritional composition containing active folic acid substances and N-acetylneuraminic acid described in the present invention, the mass ratio of the active folic acid substances to the N-acetylneuraminic acid is (0.0005~0.007):(1~5).

[0060] In some preferred embodiments, in the nutritional composition containing active folic acid substances and N-acetylneuraminic acid of the present invention, the mass ratio of the active folic acid substances to the N-acetylneuraminic acid is (0.0005-0.007):1, for example, it can be 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 substances and N-acetylneuraminic acid described in the present invention consists of active folic acid substances and N-acetylneuraminic acid; and in the nutritional composition, the mass ratio of the active folic acid substances to the N-acetylneuraminic acid is (0.0005~0.007):(1~5).

[0062] The nutritional composition containing active folic acid substances and N-acetylneuraminic acid described in the present invention is usually an artificially synthesized or compounded composition, that is, it is not a natural composition.

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

[0064] In the nutritional composition containing active folic acid substances and fucosyllactose of the present invention, the active folic acid substances and the fucosyllactose are the main effective ingredients in the nutritional composition, that is, the nutritional composition mainly relies on the active folic acid substances and fucosyllactose contained therein to exert specific physiologically active functions. The active folic acid substances are as described in the above-mentioned Part II.

[0065] In some embodiments, the fucosyllactose described herein comprises 2'-fucosyllactose.

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

[0067] The present invention does not particularly limit the source of the specific fucosyllactose. Typically, it can be synthesized by common chemical synthesis methods in the art, such as by glycosylation reaction between a lactose acceptor and a fucosyl donor. It can also be obtained by microbial fermentation methods, such as using exogenously added lactose as a substrate and 5'-diphosphate guanosine-fucose disodium salt formed by the microorganism's own metabolic pathway as a precursor to synthesize 2'-fucosyllactose under the action of fucosyltransferase.

[0068] In order to obtain better intake by mothers during pregnancy and / or lactation to help the growth of offspring and / or the antioxidant effect of offspring, in some embodiments, in the nutritional composition containing active folic acid substances and fucosyllactose described in the present invention, the mass ratio of the active folic acid substances to the fucosyllactose is (0.0001~0.0015):(0.5~5).

[0069] In some preferred embodiments, in the nutritional composition containing active folic acid substances and fucosyllactose according to the present invention, the mass ratio of the active folic acid substances to the fucosyllactose is (0.0001-0.0015):1, for example, it can be 0.0001:1, 0.0002:1, 0.0003:1, 0.0004:1, 0.0005:1, 0.0006:1, 0.0 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 substances and fucosyllactose described in the present invention consists of active folic acid substances and fucosyllactose; and in the nutritional composition, the mass ratio of the active folic acid substances to the fucosyllactose is (0.0001~0.0015):(0.5~5).

[0071] The nutritional composition containing active folic acid substances and fucosyllactose described in the present invention is usually an artificially synthesized or compounded composition, that is, it is not a natural composition.

[0072] V. Uses of helping offspring grow and / or helping offspring resist oxidation

[0073] The present invention proposes that pregnant and / or lactating mothers take active folic acid substances, a combination of active folic acid substances and N-acetylneuraminic acid, or a combination of active folic acid substances and fucosyllactose, which is helpful for the growth of their offspring and / or helps to improve the antioxidant capacity of their offspring. Moreover, when active folic acid substances are combined with N-acetylneuraminic acid or fucosyllactose in a certain ratio, the above effects are better.

[0074] The helping of offspring growth and helping offspring anti-oxidation described in the present invention are not intended to treat or prevent diseases.

[0075] Furthermore, the present invention provides the use of active folic acid substances, nutritional compositions containing active folic acid substances and N-acetylneuraminic acid, and nutritional compositions containing active folic acid substances and fucosyllactose in the preparation of foods that help the growth of offspring and / or help the offspring's body resist oxidation, wherein the foods are taken by the mother during the pregnancy and / or lactation period of the offspring to exert their effects, and such effects are not only directed at the fetus in the mother's body and the infant who consumes breast milk, but can also continue to the childhood of the offspring and exert a lasting effect on the offspring. Therefore, the offspring described in the present invention include offspring in the fetal period and / or offspring in the infant period and optional offspring in the childhood period.

[0076] The infant offspring of the present invention can be fed with breast milk. In some embodiments, the infant offspring of the present invention is completely fed with breast milk or mainly fed with breast milk. Furthermore, the active folic acid substance, the nutritional composition containing active folic acid substance and N-acetylneuraminic acid, the nutritional composition containing active folic acid substance and fucosyllactose, and the food containing active folic acid substance or its nutritional composition are ingested by the mother and play its role in helping the growth of the offspring body and / or helping the offspring body to resist oxidation through the mother-to-child transmission pathway.

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

[0078] In some embodiments, the helping the offspring's body growth includes helping the offspring gain weight, helping the offspring gain body length, helping the offspring gain grip strength, and helping the offspring gain endurance.

[0079] In some embodiments, the helping the offspring's body growth is helping the offspring gain weight, helping the offspring gain body length, helping the offspring gain grip strength, or helping the offspring gain endurance.

[0080] In some embodiments, helping the offspring to resist oxidation includes increasing the SOD content in the offspring.

[0081] In some embodiments, helping the offspring to resist oxidation includes increasing the SOD content in the offspring's serum.

[0082] Known oxidative stress is the result of an imbalance in the ratio of pro-oxidants and antioxidants in cells. Free radicals, non-radical reactive oxygen species (ROS) and reactive nitrogen species (RNS) are collectively referred to as oxidants, which easily lead to free radical chain reactions. Antioxidants, including, for example, superoxide dismutase (SOD), catalase, vitamin C, microorganism E, carotenoids, etc., can neutralize excess free radicals and protect cells from the harmful effects of oxidants (Panfoli I, Candiano G, Malova M, DeAngelis 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 to be a major factor in the pathogenesis of many cardiovascular and nervous system diseases, malignant tumors, diabetes, aging, inflammation, etc. (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.). At the same time, studies have shown that oxidative stress is involved in the pathogenesis of early developmental brain damage caused by hyperoxia, hypoxia-ischemia, drugs, and mechanical damage. Oxidative stress is one of the factors that cause brain damage during brain development and neural development (Ikonomidou C, Kaindl AM. Neuronal death and oxidative stress in the developing brain. Antioxid Redox Signal. 2011 Apr15; 14(8): 1535-50.).

[0083] However, the present invention finds that when the mother in pregnancy and / or lactation period takes active folic acid substances, the combination of active folic acid substances and N-acetylneuraminic acid, or the combination of active folic acid substances and fucosyllactose, the content of the antioxidant SOD in the body of the offspring can be increased, and the antioxidant capacity of the body can be further increased. Therefore, the present invention believes that when the mother in pregnancy and / or lactation period takes active folic acid substances, the combination of active folic acid substances and N-acetylneuraminic acid, the combination of active folic acid substances and fucosyllactose, or the food containing the above substances or substance combinations, it can be beneficial to maintain the health of the brain and nervous system of the offspring to a certain extent, and can even alleviate or respond to brain damage caused by oxidative stress. The invention is not intended to treat or prevent diseases.

[0084] In some embodiments, the food of the present invention is infant food, children's food, adolescent food or adult food.

[0085] In some preferred embodiments, the food of the present invention is food for pregnant women or 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 by 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 beverage, coffee beverage, fruit beverage, etc.; the dairy product includes milk powder, cheese, yogurt, liquid milk, etc.

[0087] In some embodiments, the food is a health food, such as various types of oral preparations; illustratively, the oral preparations can be tablets, pills, granules, powders, capsules, oral liquids, and the like.

[0088] The present invention does not particularly limit the specific absolute content of the active folic acid substance, the N-acetylneuraminic acid, and the fucosyllactose in the food, as long as the requirements of local food-related laws and regulations are met.

[0089] Depending on the type of food and the final needs of the applicable object, in some embodiments, the food also contains any one or more of the following ingredients: plant product ingredients, animal dairy product ingredients, animal meat product ingredients, functional added ingredients and any acceptable excipients.

[0090] As for the ingredients of plant products, examples include fruits such as figs, pomegranates, kiwis, tangerines, oranges, pineapples, strawberries, apples, bananas, grapes, pears, cherries, blueberries, blackberries, black currants, 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; and some botanical Chinese medicinal materials or their extracts that are both medicine and food.

[0091] As for animal dairy ingredients, examples include fresh milk from cows, sheep, etc., as well as reprocessed dairy products such as whole milk powder, skim milk powder, concentrated whey protein powder, desalted whey powder, whey protein powder, hydrolyzed whey protein powder, and casein powder.

[0092] Examples of animal meat ingredients include meat ingredients from pigs, cattle, sheep, aquatic animals or poultry.

[0093] Functional added ingredients include vitamin supplements, mineral supplements, nucleotide supplements, dietary fiber, functional polyunsaturated fatty acid supplements, and the like.

[0094] As for any acceptable excipients, examples include 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.

[0095] Example

[0096] The embodiments of the present invention will be described in detail below in conjunction with 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 under conventional conditions or conditions recommended by the manufacturer. Unless otherwise specified, the materials or instruments used are all conventional products that can be obtained commercially.

[0097] 1. Test materials

[0098] 1.1. Experimental animals and groups

[0099] 120 8-week-old sexually mature SPF female rats and 120 SPF male rats were selected; purchased from Hangzhou Medical College, animal certificate number 20240318Aazz0100000836, production license number: SCXK (Zhejiang) 2024-002. Feeding conditions: Animals were raised in a barrier environment, with an indoor temperature of 25±1℃, humidity of 45±5%, free access to drinking water, and a 12h light-dark alternation environment. This experiment passed the animal experiment ethics review of Southeast University; ethics number: 20240316003.

[0100] After 3 days of adaptive feeding, female and male rats were placed in the same cage at a ratio of 1:1. The intervention started when the mother rat showed vaginal plugs, and the mother rats were continuously gavaged until the offspring rats were weaned. The experimental group was divided into groups and given the corresponding doses of sample aqueous solution, and the control group was given the corresponding dose of normal saline, gavaged once a day for 6 consecutive weeks, and each dose group was given maintenance feed. 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. The weight of the mother rats, the height and weight of the offspring rats were monitored weekly during the gavage process.

[0101] Table 1 Oral doses for experimental animals

[0102]

[0103] 1.2. Instruments, consumables and reagents

[0104] The consumables, reagents and experimental instruments used in the experiment are shown in Tables 2 and 3.

[0105] Table 2 Main experimental consumables and reagents

[0106] name company SOD Detection Kit Nanjing Jiancheng Biotechnology Co., Ltd. 6S-5-Methyltetrahydrofolate calcium Wuxi Taxus Pharmaceutical Co., Ltd. N-acetylneuraminic acid CABIU Biotech (Wuhan) Co., Ltd. 2'-fucosyllactose DSM SPF growth and breeding feed for rats and mice Pizhou Xiaohe Technology Development Co., Ltd.

[0107] Table 3 Main experimental instruments

[0108] Instrument Name company Automatic Microplate Reader MK3 THERMO Electronic balance PTX-FA110S Huazhi (Fujian) Electronic Technology Co., Ltd. Desktop high speed refrigerated centrifuge Xiangyi XR-6C Rotarod Fatigue Tester for Rats and Mice Shanghai Xinruan Technology Co., Ltd. Mouse Grip Strength Meter-XR501 Shanghai Xinruan Technology Co., Ltd.

[0109] 2. Detection Methods

[0110] 2.1. Monitoring and recording of weight and height of mother mice and offspring

[0111] (1) Maternal weight records: The weight changes of maternal mice were recorded at enrollment (week 0), 1 week and 2 weeks of intervention, 0 week, 1 week, 2 weeks, and 3 weeks after delivery.

[0112] (2) Weight record of offspring: record the weight changes of offspring at 0, 1, 2, and 3 weeks after birth.

[0113] (3) Record of body length of offspring: Record the changes in body length of offspring at 0, 1, 2, and 3 weeks after birth.

[0114] 2.2. Roller test (rotating rod fatigue test)

[0115] The rat rotarod fatigue experiment is divided into a learning period and a test period, which is used to evaluate the effect of the sample on the coordination ability and fatigue tolerance of the rats. After weaning, the rats are placed on the rotarod fatigue instrument every day for learning for 1-4 days, and tested on the 5th day. During the learning period, the rotarod speed is set to 20r / min and the time is 10min. After the learning period of the rats, the test experiment is carried out, and the test speed is set to 40r / min. The time when the rats fall, that is, the rats' roller latency (s), is recorded. The test experiment is repeated 3 times and the average value is calculated.

[0116] 2.3. Grip strength test of rats

[0117] Before the test, the offspring was brought into the test laboratory and placed for 1.5 hours to adapt to the environment. The offspring was gently taken out of the cage, and the tail was gently grasped. The offspring was allowed to grasp the digital dynamometer, and the tail was gently pulled away in parallel. When the maximum force was applied to the offspring, the grip dynamometer reading was recorded, and the measurement was repeated three times to calculate the peak grip force (N), peak time (s) and grip duration (s) to evaluate the muscle development of the offspring.

[0118] 2.4. Serum collection and index detection of mother and offspring mice

[0119] After the experiment, the mother mice were anesthetized by intraperitoneal injection of 5% sodium pentobarbital solution, and blood was collected from the abdominal aorta, centrifuged at 3000r / min for 5min, and the serum was separated and stored at -80°C. After weaning, one offspring was selected from each mother mouse, anesthetized by intraperitoneal injection of 5% sodium pentobarbital solution, and two blood samples were collected from the abdominal aorta, one of which was placed in an anticoagulant tube (sent for inspection on the same day) and the other in a procoagulant tube, centrifuged at 3000r / min for 5min, and the serum was separated and stored at -80°C.

[0120] (1) Detection of maternal serum blood glucose (Glu): After the maternal serum was collected, the maternal serum blood glucose level was detected using a fully automatic biochemical analyzer using the glucose oxidase method.

[0121] (2) Detection of glycosylated albumin (GA) in maternal rat serum: The GA content in maternal rat serum was detected using an automatic microplate reader and GA enzyme-linked immunosorbent assay (ELISA).

[0122] (3) Detection of FA in maternal rat serum: The FA content in maternal rat serum was detected using a fully automatic microplate reader and reference FA enzyme-linked immunosorbent assay (ELISA).

[0123] (4) Detection of FA in serum of offspring mice: The FA content in serum of offspring mice was detected using a fully automatic microplate reader and reference FA enzyme-linked immunosorbent assay (ELISA).

[0124] (5) Superoxide dismutase (SOD) detection in the blood of offspring mice: The SOD content in the serum of offspring mice was detected using a fully automatic microplate reader with reference to the SOD enzyme-linked immunosorbent assay (ELISA) method.

[0125] 3. Test results

[0126] 3.1. Weight growth index of mother mice and offspring

[0127] Table 4. Body weight of female mice (g)

[0128]

[0129] Before intervention with different samples, there was no significant difference in the weight of the maternal mice, and the results are shown in Table 4. Compared with the control group, there was no significant difference in the weight changes of the maternal mice in Examples 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, and 11 during pregnancy and 2 weeks after delivery; 3 weeks after delivery, the weight of the maternal mice in Example 1 was significantly lower than that in the control group, indicating that the low-dose active folic acid group has a certain promoting effect on the recovery of the weight of the maternal mice after delivery.

[0130] Table 5: Weight of offspring (g)

[0131]

[0132] The weight index during infancy is an important indicator for measuring their healthy growth and development. The results in Table 5 show that after continuous intervention, there was no significant difference in the birth weight of the offspring of most examples compared with the control group, and the birth weight of the offspring of Example 7 was significantly higher than that of the control group. With the progress of breastfeeding, one week after birth, the weight of the offspring of Examples 2, 5, 6, 7, 10, and 11 was significantly higher than that of the control group; two weeks after birth, the weight of the offspring of Examples 2, 4, 6, 7, 8, 9, 10, and 11 was significantly higher than that of the control group; three weeks after birth, the weight of the offspring of Examples 4, 6, 7, 8, 10, and 11 was significantly higher than that of the control group.

[0133] 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 weight of the offspring mice after birth; the high-dose N-acetylneuraminic acid group showed a significant trend of promoting weight gain from 2 weeks after birth; the high-dose 2'-fucosyllactose can promote the rapid growth of the weight of the offspring mice after birth.

[0134] In addition, the present invention unexpectedly discovered that: after intervention with a mixture of a high dose of active folic acid plus a low dose of N-acetylneuraminic acid, a significant trend of promoting weight gain in offspring mice was shown starting from 2 weeks after birth, and the effect was better than the effect of a single substance, showing a synergistic trend; after intervention with a high dose of active folic acid plus a low- and high-dose combination of 2'-fucosyllactose, the rapid growth of weight of offspring mice after birth was significantly promoted, and the 2'-fucosyllactose dosage group showed a dose-dependent trend.

[0135] Table 6 Results of the body length of offspring (cm)

[0136]

[0137] The height index of infants and young children is an important index to measure their healthy growth and development. The results in Table 6 show that after continuous intervention, the height of offspring mice of different embodiments at birth showed different differences compared with the control group, among which the height of offspring mice of embodiments 5, 7, 10, and 11 was significantly higher than that of the control group, and there was no significant difference between the other embodiments and the control group; 1 week after birth, the height of offspring mice of embodiments 4, 5, 6, 7, 10, and 11 was significantly higher than that of the control group; 2 weeks after birth, the height of offspring mice of embodiments 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, and 11 was significantly higher than that of the control group; 3 weeks after birth, the height of offspring mice of embodiments 2, 3, 4, 5, 6, 8, 9, and 11 was significantly higher than that of the control group.

[0138] The above experimental results show that compared with the control group, the high-dose group of active folic acid can promote the rapid growth of the body length of the offspring mice, which is reflected in 2 weeks after birth; the low- and high-dose groups of N-acetylneuraminic acid show a significant trend of promoting the increase in the body length of the offspring mice from 1 to 2 weeks after birth; 2'-fucosyllactose can promote the rapid growth of the body length of the offspring mice after birth.

[0139] In addition, the present invention unexpectedly discovered that: after intervention with a mixture of a high-dose active folic acid plus a high-dose N-acetylneuraminic acid group, there was a significant trend of promoting the rapid growth of the body length of the offspring starting from 2 weeks after birth; after intervention with a high-dose active folic acid plus a low- and high-dose 2'-fucosyllactose combination, the rapid growth of the body length of the offspring after birth was significantly promoted.

[0140] 3.2. Roller test (rotating rod fatigue test)

[0141] Table 7 Roller latency of rats (s)

[0142]

[0143] The longer the roller latency of the offspring, the stronger the coordination and grasping ability of the offspring. The results in Table 7 show that compared with the control group, the roller latency of the offspring of Examples 3, 4, 5, 6, 7, 8, 9, 10, and 11 has different degrees of improvement, among which the roller latency of the offspring of Examples 6 and 7 has the highest increase. The results show that compared with the blank control group, the roller latency of the offspring of different doses of active folic acid alone was not significantly improved, and the roller latency of the offspring of different doses of N-acetylneuraminic acid alone and different doses of 2'-fucosyllactose alone was improved to different degrees. In addition, the present invention unexpectedly discovered that the combination of a low-dose group of N-acetylneuraminic acid plus a high-dose group of active folic acid performed better after intragastric administration than the single-dose group, and the effect was better than the effect of a high-dose group of N-acetylneuraminic acid plus a high-dose group of active folic acid. The roller latency of the offspring mice increased significantly after intragastric administration of the combination of a low-dose group of active folic acid and a low-dose group of 2'-fucosyllactose, indicating that it has a certain effect in promoting the coordinated grasping ability of the offspring mice.

[0144] Table 8 Results of the grip strength test of rats

[0145]

[0146] The higher the peak value of gripping force, the stronger the gripping ability of the rat is, and the stronger its muscle strength is; the longer the peak moment and the longer the gripping time are, the stronger the endurance of the rat is. The results in Table 8 show that compared with the control group, the peak value of gripping force of the rats in Examples 3, 4, 5, 6, and 9 is significantly improved; the peak moment of the rats in Examples 1, 5, 6, and 8 is significantly higher than that in the control group, and the gripping time of the rats in Examples 1, 3, 5, 6, and 9 is significantly higher than that in the control group. The results showed that intervention with the low-dose active folic acid group could significantly increase the peak grasping moment and grasping duration of the offspring mice, and had a certain promoting effect on the grip strength and endurance of the offspring mice; the low-dose N-acetylneuraminic acid group could significantly increase the peak grasping force and grasping duration of the offspring mice, and different doses of 2'-fucosyllactose could increase the peak grasping force, peak moment and grasping duration of the offspring mice, indicating that it had a positive promoting effect on the grip strength and endurance development of the offspring mice; in addition; intervention with the low-dose active folic acid group plus the low-dose 2'-fucosyllactose combination could significantly increase the peak grasping force and grasping duration of the offspring mice, and had a certain promoting effect on the grip strength and endurance of the offspring mice.

[0147] 3.3. Blood index results of maternal mice

[0148] Table 9 Maternal serum Gl u Test results (mmol / L)

[0149] Grouping Glu Blank control 12.00±3.43 Example 1 9.58±1.88 Example 2 10.54±2.05 Example 3 10.31±1.74 Example 4 10.21±1.86 Example 5 10.45±3.57 Example 6 10.53±1.62 Example 7 10.02±2.98 Example 8 10.20±0.79 Example 9 10.37±1.66 Example 10 10.15±1.16 Embodiment 11 10.17±1.63

[0150] Abnormal blood sugar levels during pregnancy have adverse effects on both the mother and the fetus. The results of the maternal blood glucose test after the intervention are shown in Table 9: Compared with the control group, the maternal blood glucose levels of Examples 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, and 11 all decreased to a certain extent, and there was no significant difference among the groups (P>0.05).

[0151] Table 10 GA test results of maternal rat serum (mmol / L)

[0152] Grouping GA GA% Blank control 45.97±6.03 29.72±2.87 Example 1 46.08±6.79 30.20±1.75 Example 2 51.63±8.14 30.11±1.72 Example 3 44.04±9.05 29.17±1.59 Example 4 44.89±11.25 29.67±1.79 Example 5 47.63±10.42 29.28±1.49 Example 6 49.62±10.56 29.42±1.71 Example 7 43.75±10.62 28.46±1.51 Example 8 52.18±11.29 30.27±1.81 Example 9 56.13±9.37 29.81±2.78 Example 10 47.18±10.39 28.94±1.04 Embodiment 11 49.89±9.35 28.99±1.62

[0153] Serum glycosylated albumin GA is an indicator of the average blood sugar in the past 2 to 3 weeks. The results of maternal GA detection are shown in Table 10. 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 show that during the intervention period, intervention with different doses of active folic acid, N-acetylneuraminic acid, 2'-fucosyllactose and their combination will not produce the risk of gestational hyperglycemia, and have no significant effect on the blood sugar level during pregnancy.

[0154] Table 11 FA test results of maternal rat serum (μg / L)

[0155] Grouping FA Blank control 8.71±2.58 Example 1 8.41±2.51 Example 2 10.81±2.74 Example 3 10.32±2.50 Example 4 9.22±2.29 Example 5 11.73±3.13 Example 6 10.23±3.41 Example 7 9.33±2.91 Example 8 11.38±2.43 Example 9 10.12±3.74 Example 10 11.85±3.19 Embodiment 11 9.08±3.18

[0156] After the intervention, the results of the serum folate content of the maternal rats are shown in Table 11: Compared with the control group, the serum folate content of the maternal rats in Examples 2, 3, 4, 5, 6, 7, 8, 9, 10, and 11 all showed an increasing trend to varying degrees, but the difference was not statistically significant (P>0.05). The supplementation of folic acid and the composition did not lead to a significant increase in the serum folate of the maternal rats. The possible reason is that folic acid is absorbed and metabolized in the body and secreted through breast milk, thereby consuming the supplemented folic acid. There was no significant difference in the folic acid in the blood of the other groups compared with the control group, because the maternal rats obtained a part of the folic acid supplement through the basic feed.

[0157] 3.4. Blood index test results of offspring mice

[0158] Table 12 Results of serum FA test in offspring mice (μg / L)

[0159]

[0160] During the experiment, the offspring obtained folic acid mainly through breast milk. The results of the offspring serum folic acid test are shown in Table 12: Compared with the control group, the serum folic acid content of the offspring in Examples 1, 2, 7, and 11 was significantly increased (P < 0.05). The results showed that the intervention of different doses of active folic acid promoted the increase of serum folic acid in offspring and showed a certain dose-dependent effect; in addition, the serum folic acid level of offspring in the high-dose active folic acid plus low-dose N-acetylneuraminic acid group was significantly increased, and the serum folic acid level of offspring in the high-dose active folic acid plus high-dose 2'-fucosyllactose group was significantly increased and higher than the levels of the substance monomer intervention group.

[0161] Table 13 Results of serum SOD test in offspring mice (U / mL)

[0162]

[0163] The higher the superoxide dismutase SOD value, the higher the antioxidant capacity of the body. The results of the offspring mouse serum SOD test are shown in Table 13. Compared with the control group, the serum SOD values ​​of the offspring mice in Examples 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, and 11 were significantly improved; among them, the serum SOD values ​​of the offspring mice in Examples 8 and 11 were higher than those in Examples 2, 4, and 6.

[0164] The above experimental results show that: compared with the blank control group, the serum SOD values ​​of offspring mice were significantly improved by gavage of different doses of active folic acid alone, different doses of N-acetylneuraminic acid alone, and 2'-fucosyllactose alone, and all showed a trend of increasing effect with increasing dose. In addition, the present invention unexpectedly found that the serum SOD values ​​of offspring mice after gavage of the composition of active folic acid plus N-acetylneuraminic acid were higher than the effect of gavage alone, and the composition of the high-dose group of active folic acid and the high-dose group of N-acetylneuraminic acid can significantly improve the antioxidant capacity of offspring mice; the serum SOD values ​​of offspring mice after gavage of the composition of active folic acid plus 2'-fucosyllactose were higher than the effect of gavage alone, and the composition of the high-dose group of active folic acid and the high-dose group of 2'-fucosyllactose can significantly improve the antioxidant capacity of offspring mice.

Claims

1. Use of active folic acid substances in preparing foods that are ingested by mothers during pregnancy and / or lactation to help the growth of offspring and / or help the offspring's body resist oxidation.

2. Use of a nutritional composition containing active folic acid substances and N-acetylneuraminic acid in preparing a food that is ingested by mothers during pregnancy and / or lactation and that helps the growth of offspring and / or helps the offspring's body resist oxidation.

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

4. Use of a nutritional composition containing active folic acid and fucosyllactose in preparing a food that is ingested by a mother during pregnancy and / or lactation and that helps the offspring's body grow and / or helps the offspring's body resist oxidation.

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

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

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

8. The use according to any one of claims 1 to 7, characterized in that The helping the offspring's body growth includes at least one of helping the offspring to increase weight, helping the offspring to increase body length, helping the offspring to increase grip strength, and helping the offspring to increase endurance.

9. The use according to any one of claims 1 to 8, characterized in that The helping the offspring body to resist oxidation includes increasing the SOD content in the offspring body.

10. The use according to any one of claims 1 to 9, characterized in that The food helps maintain the brain health of the offspring by helping the offspring's body to resist oxidation and inhibit the offspring's body's oxidative stress.

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 woman food and postpartum woman food.

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