A nutritional composition and its use for assisting in the improvement of memory impairment

Abstract

The present application belongs to the technical field of nutrient research, and particularly relates to a kind of nutrient composition and the use of auxiliary improvement of memory impairment thereof.The nutrient composition provided by the present application comprises the following two necessary components: i) lysophosphatidyl ethanolamine;ii) phosphoester serine;And, in the nutrient composition, the mass ratio of the lysophosphatidyl ethanolamine to the phosphoester serine is 1:(0.1-2000).After lysophosphatidyl ethanolamine and phosphoester serine are combined, memory impairment can be synergistically assisted to improve, repair the damage of cholinergic system in the body, and also effectively improve the decline of behavioral ability and cognitive ability accompanied by memory impairment.

Description

Technical Field

[0001] This invention belongs to the field of nutrient research technology, and relates to a nutritional composition and its use in assisting to improve memory impairment, and more specifically to a nutritional composition and its use in assisting to improve memory impairment and / or memory impairment accompanied by a decline in abilities. Background Technology

[0002] Impaired memory is a common cognitive dysfunction, referring to a decline in the ability to acquire, store, retrieve, or recall memories. It is mainly manifested as forgetfulness, weak memory, difficulty in information retrieval, and short-term memory decline. In severe cases, it can affect daily life, work, and learning efficiency. The causes of impaired memory are complex and diverse, including physiological factors such as the natural decline in brain function due to aging, insufficient sleep, excessive fatigue, and excessive mental stress, as well as pathological factors such as mild cognitive impairment, brain injury, early stages of neurodegenerative diseases, cerebrovascular diseases, and nutritional deficiencies. Among these, nutritional imbalance is one of the important controllable factors leading to impaired memory.

[0003] With the accelerating pace of modern life, increasingly prominent issues such as unbalanced diets and irregular work and rest schedules, memory impairment is showing a trend of affecting younger and more widespread individuals. Not only are middle-aged and elderly people significantly affected, but teenagers and working professionals also frequently experience varying degrees of memory decline due to factors such as prolonged late nights, mental stress, and insufficient nutrient intake, which adversely impacts their personal quality of life and social productivity.

[0004] Currently, interventions for memory impairment mainly include behavioral interventions, pharmacological interventions, and nutritional interventions. Among these, pharmacological interventions often have side effects and can only provide symptomatic relief, failing to fundamentally improve brain memory function. For example, Donanemab, a monoclonal antibody drug recently approved by the FDA for the clearance of Aβ plaques, had an adverse reaction rate of ≥5% in treated subjects, which was ≥2% higher than in the placebo group. The most prominent side effects included edema and bleeding. Behavioral interventions (such as memory training) are slow to take effect and require long-term adherence, resulting in poor compliance.

[0005] In recent years, nutritional intervention has become a research hotspot for improving impaired memory due to its advantages such as safety, convenience, lack of obvious adverse reactions, and long-term implementation. Studies have confirmed that the normal physiological functions of the brain and the processes of memory formation and storage depend on the synergistic support of various nutrients. Among them, milk-derived nutrients, rich in various active nutrients and easily absorbed and utilized by the human body, have become a core nutritional source for improving impaired memory. Components such as whey protein, casein, milk fat globule membrane, lactoferrin, milk-derived polypeptides, lactose, milk-derived vitamins, and minerals can improve memory levels and delay memory decline or decay by improving cerebral blood circulation, promoting neuronal development, repairing synaptic damage, inhibiting oxidative stress, and regulating neurotransmitter secretion. For example, reference 1 uses milk fat globule membrane rich in phospholipids to prepare formula milk powder to promote brain development, improve learning ability, and alleviate cognitive decline; reference 2 uses lactoferrin to prevent impaired learning ability, mental and behavioral impairment, memory impairment, or reduced attention span.

[0006] The normal maintenance of memory function is closely related to brain energy metabolism, neurotransmitter balance, oxidative stress levels, and gut microbiota homeostasis. Milk-derived nutrients can participate in the regulation of these processes through multiple pathways. As a high-energy-consuming organ, the brain requires a continuous energy supply to maintain memory-related physiological activities. Lactose in milk can be broken down into glucose for direct use by the brain, while milk fat can be metabolized to produce ketone bodies, providing additional energy support for the brain. The synthesis and release of neurotransmitters (such as acetylcholine and dopamine) directly affect memory formation and retrieval. Amino acids such as tryptophan and tyrosine contained in whey protein and casein are important precursors for neurotransmitter synthesis, promoting neurotransmitter secretion and maintaining their balance. Oxidative stress can damage neurons and synaptic structures, leading to a decline in memory function. Lactoferrin, whey protein hydrolysates, and milk-derived vitamins (such as vitamin E and vitamin C) have significant antioxidant activity, which can protect brain memory-related tissues by scavenging free radicals and reducing oxidative damage. Furthermore, the bidirectional regulatory effect of the brain-gut axis also participates in the regulation of memory function. Components such as dairy probiotics and whey protein can regulate the composition of gut microbiota and promote gut health, thereby indirectly improving memory through the brain-gut axis. At the same time, dairy nutrients can also enhance the body's immunity and reduce the damage to brain memory function caused by inflammatory responses, further enhancing memory improvement.

[0007] Milk-derived nutrients, as a natural and high-quality source of nutrition, are rich in various bioactive nutrients and have advantages such as easy absorption, high safety, wide availability, and easy accessibility. Furthermore, some of its nutrients can work synergistically to improve memory impairment through multiple pathways, making it suitable as a core nutritional intervention ingredient for improving memory impairment. Based on this, developing a nutritional composition with milk-derived nutrients as the core, combined with other functional nutrients, for the multi-pathway and synergistic improvement of memory impairment, meets market demand and has significant practical value and promising prospects for promotion.

[0008] Phospholipids are key bioactive components of breast milk lipids, playing a crucial role in the development of the nervous system and metabolic regulation in infants and young children. Phospholipids can be divided into glycerophospholipids (PL) and sphingomyelin (SM), with PL further subdivided into lysophospholipids (LPL) and phosphatallipids. Lysophospholipids are produced through the hydrolysis of one fatty acid in the PL molecule, and the main components in breast milk are lysophosphatidylcholine (LPC) and lysophosphatidylethanolamine (LPE).

[0009] Phosphatidylserine (PS) is a naturally occurring phospholipid compound belonging to the glycerophospholipid class, widely found in animals, plants, and microorganisms. It is a core component of the cell membranes of cerebral cortex nerve cells, accounting for approximately 10%-15% of the total phospholipids in the brain, and plays a role in improving memory and neuroprotection. Specifically, phosphatidylserine can repair nerve cell membranes, maintain the integrity of nerve cell structure; promote the growth and plasticity of neural synapses; regulate the secretion of neurotransmitters; inhibit oxidative stress and neuroinflammatory responses; and assist in regulating the brain's energy metabolism. For example:

[0010] Reference 3 discloses a solid beverage containing phosphatidylserine and ω-3 fatty acids and its preparation method. When phosphatidylserine and ω-3 fatty acids are taken together, they can improve the brain function of the consumer. ω-3 fatty acids can promote the absorption of phosphatidylserine by the brain and enhance brain function. The solid beverage has a pleasant taste, a long shelf life, and is suitable for all ages.

[0011] Reference 4 discloses a composition for improving memory, made from phosphatidylserine, wolfberry, polygonatum, ginkgo, and poria. Phosphatidylserine has excellent memory-improving properties and is inexpensive and readily available. The four herbs in this combination are all traditional Chinese medicines that are both food and medicine, making them safe and effective. Combined with phosphatidylserine, they can enhance brain function, repair brain damage, and improve memory.

[0012] References:

[0013] Reference 1: CN113455551B

[0014] Reference 2: CN105435214B

[0015] Reference 3: CN110692893A

[0016] Reference 4: CN102885977B Summary of the Invention

[0017] The problem the invention aims to solve

[0018] In the past, memory impairment primarily affected middle-aged and elderly people, often accompanied by mild cognitive impairment, neurodegenerative diseases (such as Alzheimer's disease and Parkinson's disease), and memory decline caused by some cerebrovascular diseases. Currently, treatments for these diseases are not only expensive and have limited efficacy, but some also have significant side effects.

[0019] It is worth noting that memory impairment is showing a trend of affecting younger people. Influenced by factors such as work stress, irregular lifestyles, and changes in dietary habits, many young and middle-aged adults are beginning to experience memory impairment. However, these problems may not yet meet the criteria for clinical treatment, and this group often does not pay enough attention to them, rarely taking proactive measures even when they notice a slight decline in memory function. As they age, the risk of developing memory-related diseases such as Alzheimer's or Parkinson's further increases in this population.

[0020] Given that existing drugs have limited efficacy and side effects in treating memory impairment-related diseases in the elderly, and that young and middle-aged people tend to overlook early memory decline, exploring nutritional interventions to improve or delay memory loss is of great significance for promoting human health and improving quality of life.

[0021] In response, this invention provides a phospholipid nutritional composition derived from natural milk sources, mainly comprising lysophosphatidylethanolamine and phosphatidylserine. The two work synergistically to improve impaired memory without any side effects and can be consumed long-term as a nutritional supplement.

[0022] Solution for solving the problem

[0023] To address the aforementioned technical problems, the present invention provides the following technical solution:

[0024] [1]. A nutritional composition comprising the following two essential components:

[0025] i) Lysophosphatidylethanolamine;

[0026] ii) Phosphatidylserine;

[0027] Furthermore, in the nutritional composition, the mass ratio of the lysophosphatidylethanolamine to the phosphatidylserine is 1:(0.1-2000).

[0028] [2]. According to the nutritional composition described in [1], wherein the fatty acid chain of the lysophosphatidylethanolamine contains between 12 and 22 carbon atoms.

[0029] [3]. The nutritional composition according to [1] or [2], wherein the fatty acid chain in the lysophosphatidylethanolamine is located at the sn-1 position.

[0030] [4]. The nutritional composition according to any one of [1]-[3], wherein the fatty acid chain in the lysophosphatidylethanolamine is unsaturated.

[0031] [5]. The nutritional composition according to any one of [1]-[4], wherein the lysophosphatidylethanolamine is provided in the form of dairy products containing it and / or enzymatically hydrolyzed soybean lecithin.

[0032] [6]. Use of the nutritional composition according to any one of [1]-[5] in the preparation of products that help improve memory impairment and / or memory impairment accompanied by decreased abilities.

[0033] [7]. According to the use described in [6], wherein the memory impairment accompanied by a decline in ability includes one or both of a decline in behavioral ability and a decline in cognitive ability.

[0034] [8]. Use of the nutritional composition according to any one of [1]-[5] in the preparation of products having the effect of improving the function of the cholinergic system.

[0035] [9]. According to the use described in [8], wherein the improvement of cholinergic system function includes reducing the level of neurotransmitter degrading enzymes.

[0036]

[10] . Use according to any one of [6]-[9], wherein the product contains any one or more of the following ingredients: plant-based ingredients, animal dairy ingredients, animal meat ingredients, functional additives and any acceptable excipients.

[0037] The effects of the invention

[0038] This invention proposes for the first time that the combination of lysophosphatidylethanolamine and phosphatidylserine can synergistically improve memory impairment, repair damage to the cholinergic system in the body, and effectively improve the decline in behavioral and cognitive abilities that accompany memory impairment.

[0039] Meanwhile, the nutrients mentioned in this invention, lysophosphatidylethanolamine and phosphatidylserine, are both natural nutrients found in breast milk or cow's milk, suitable for long-term use, and readily accepted by people throughout their entire life cycle. The nutritional composition can be added to various types of products, including food, nutritional products, nutritional supplements, health foods, and pharmaceuticals. Detailed Implementation

[0040] The following describes embodiments of the present invention, but the present invention is not limited thereto. The present invention is not limited to the various configurations described below, and various modifications can be made within the scope of the claims. Embodiments and examples obtained by appropriately combining the technical means disclosed in different embodiments are also included in the technical scope of the present invention.

[0041] <Terminology Definition>

[0042] In this invention, "comprising," "having," "including," or "containing" can mean included or open-ended, and does 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.

[0043] In this invention, the meaning of "may" includes both performing a certain process and not performing a certain process.

[0044] In this invention, "optional" or "optionally" means that certain substances, components, execution steps, application conditions, etc., are used or not used.

[0045] In this invention, the numerical ranges represented by "value A ~ value B", "value A - value B", and "value A above / below" refer to the ranges including the endpoint values ​​A and B.

[0046] In this invention, the term "about" is used to define that the numerical ranges and parameters of this invention are approximate values, and the relevant values ​​in the specific embodiments 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 the term "about". Here, "about" generally means that the actual value is within ±5%, ±3%, ±1%, or ±0.5% of a specific value or range. Furthermore, the values ​​and ranges appearing in this invention should be understood to include systematic errors that are unavoidable in industrial production.

[0047] In this invention, terms such as "some specific / preferred embodiments," "other specific / preferred embodiments," and "implementation" refer to specific elements (e.g., features, structures, properties, and / or characteristics) related to a particular embodiment that are included in at least one of the embodiments described herein, and may or may not be present in other embodiments. Furthermore, it should be understood that these elements may be combined in any suitable manner in various embodiments.

[0048] In this invention, all unit names used are international standard unit names, and unless otherwise stated, the "%" used refers to weight or mass percentage content.

[0049] In this invention, "teenagers" refers to the human group aged 7-18.

[0050] In this invention, "young adult" refers to the human group aged 19-40.

[0051] In this invention, "middle-aged and elderly" refers to the human group aged 41 and above, including middle-aged people aged 41-65 and elderly people aged 65 and above.

[0052] In this invention, "animal milk" refers to the fluid obtained from the mammary glands of mammals during lactation. In this invention, "lysophosphatidyl ethanolamine (LysoPE, LPE)" is a glycerophospholipid composed of a glycerol backbone, a fatty acid chain, a phosphate group, and an ethanolamine head group. Compared to phosphatidyl ethanolamine, it lacks a fatty acid chain at the sn-1 or sn-2 position of its glycerol backbone.

[0053] In this invention, for ease of description of glycerophospholipids, the following characters are used to refer to different types of fatty acids: straight-chain fatty acids with a chain length of 18 carbon atoms and no carbon-carbon double bonds (18:0), such as stearic acid; straight-chain fatty acids with a chain length of 18 carbon atoms and one carbon-carbon double bond (18:1), such as oleic acid; straight-chain fatty acids with a chain length of 18 carbon atoms and two carbon-carbon double bonds (18:2), such as linoleic acid; and other fatty acid chain lengths are treated similarly. In this invention, for specific lysophosphatidylethanolamines, the format "LPE + the above characters" is used to indicate the type of lysophosphatidylethanolamine with different fatty acid chains, such as LPE18:0, LPE18:1, LPE18:2, etc.

[0054] In this invention, "LPE(18:2(9Z,12Z) / 0:0)" refers to a lysophosphatidylethanolamine molecule characterized by the following structural features: linoleic acid (18:2(9Z,12Z)) is attached to the sn-1 position of glycerol, while a hydroxyl group (-OH) is present at the sn-2 position, indicating that this position does not contain a fatty acid chain (represented as 0:0). Here, 18:2(9Z,12Z) represents a fatty acid chain consisting of 18 carbon atoms and containing two cis double bonds (located at the 9th and 12th carbon atoms, respectively), i.e., linoleic acid; 0:0 indicates that the corresponding position lacks a fatty acid chain and is replaced by a hydroxyl group.

[0055] 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.

[0056] (Nutritional composition)

[0057] The nutritional composition provided by this invention comprises the following two essential components: i) lysophosphatidylethanolamine and ii) phosphatidylserine;

[0058] Furthermore, in the nutritional composition, the mass ratio of the lysophosphatidylethanolamine to the phosphatidylserine is 1:(0.1-2000).

[0059] This invention does not impose any special requirements on the source of lysophosphatidylethanolamine, as long as its source or form of use meets the requirements of local laws and regulations.

[0060] For example, it can be prepared through physical separation and extraction, chemical synthesis, enzymatic hydrolysis, and biosynthesis. It can be isolated and extracted from phospholipid-rich milk sources, or its natural phosphatidylethanolamine or natural phospholipids containing phosphatidylethanolamine can be enzymatically hydrolyzed using phospholipases. For example, deacetylation using phospholipase A2 can yield sn-1-acyl-LPE. Furthermore, lysophosphatidylethanolamine with a specific acyl group composition can be obtained using a combination of methods, such as the chemical-enzyme hybridization method.

[0061] In some embodiments, the lysophosphatidylethanolamine of the present invention can be separated and extracted from a phospholipid-rich milk source, wherein the phospholipid-rich milk source can be a milk fat globule membrane, and the separation and extraction method can be membrane separation.

[0062] In some embodiments, the lysophosphatidylethanolamine of the present invention is provided in the form of dairy products containing it (e.g., buttermilk products, phospholipid-containing milk proteins, milk phospholipid products, whole milk, whole milk powder, and / or phospholipid-containing cream products, etc.) and / or enzymatically hydrolyzed soybean lecithin. The content of lysophosphatidylethanolamine varies in each source form. For example: in the buttermilk products, the content of lysophosphatidylethanolamine, on a dry weight basis, can be 1-3000 mg / 100g, preferably 1-1000 mg / 100g; wherein the content of LPE (18:2(9Z,12Z) / 0:0) can be 1-1000 mg / 100g, preferably 10-500 mg / 100g; in the phospholipid-containing milk proteins, the content of lysophosphatidylethanolamine, on a dry weight basis, can be 0.1-1000 mg / 100g, preferably 0.5-500 mg / 100g. 0g; wherein the content of LPE (18:2(9Z,12Z) / 0:0) can be 0.1-300mg / 100g, preferably 0.5-200mg / 100g; in the phospholipid-containing cream product, on a dry weight basis, the content of lysophosphatidylethanolamine can be 0.0001-100mg / 100g liquid, preferably 0.001-50mg / 100g liquid; wherein the content of LPE (18:2(9Z,12Z) / 0:0) can be 0.0001-1mg / 100g liquid, preferably 0.0005-0.5mg / 100g liquid.

[0063] In other embodiments, the lysophosphatidylethanolamine of the present invention is provided in pure form (commercially available product) with a purity of 99% or higher.

[0064] The phosphatidylserine described in this invention, also known as serine phospholipid, abbreviated as PS, mainly consists of three parts: a glycerol backbone as the head, and two relatively long hydrocarbon chain groups as the tail. The head is formed by the combination of serine residues and phosphate residues, followed by a glycerol hydroxyl group at the C-3 position. The tail is composed of two glycerol hydroxyl groups and a relatively long hydrocarbon chain formed by the combination of fatty acids to form an ester. The C-2 carbon chain on the glycerol is longer than the C-1 carbon chain and has more unsaturated bonds. PS is amphiphilic: the negatively charged head is hydrophilic, while the tail, composed of fatty acids, is lipophilic. Phosphatidylserine refers to a group of compounds, not a single component, because the acyl residues in products extracted from raw materials from different sources vary considerably.

[0065] PS is widely found in the biofilms of animals, plants, and microorganisms. Therefore, this invention does not specifically limit the source of phosphatidylserine. For example, it can be derived from animals (e.g., livestock and poultry meat, livestock and poultry offal such as liver and brain, fish, etc.), plants (e.g., soybeans, leeks, etc.), and microorganisms (e.g., Escherichia coli, yeast, etc.). Simultaneously, this invention does not specifically limit the extraction process of phosphatidylserine. For example, crude phospholipids can be extracted first using methods such as chloroform-methanol-water extraction, hexane-isopropanol extraction, ethyl acetate-ethanol extraction, or tert-butyl methyl ether extraction. Subsequently, phosphatidylserine can be purified using methods such as thin-layer chromatography, silica gel column chromatography, or high-performance liquid chromatography. Furthermore, phosphatidylserine can also be synthesized using enzymatic conversion methods (e.g., phosphatidylcholine undergoes a displacement reaction between choline and serine via the action of phospholipase D). For example, the PS content in each source form can typically be 1-99% by mass.

[0066] Phosphatidylserine can be obtained commercially, such as from International Flavors & Fragrances (IFF).

[0067] In some embodiments, the necessary component shown in i) comprises at least lysophosphatidylethanolamine with a fatty acid chain length of 12-22 carbon atoms, such as LPE14:1, LPE16:0, LPE17:1, LPE17:2, LPE18:0, LPE18:1, LPE18:2, LPE22:1, LPE22:2 and / or LPE22:6, which are present in milk sources; preferably, the necessary component shown in i) comprises at least lysophosphatidylethanolamine with a fatty acid chain length of 18 carbon atoms; preferably, the fatty acid chain in the lysophosphatidylethanolamine is unsaturated.

[0068] In some preferred embodiments, the fatty acid chain in the lysophosphatidylethanolamine with a fatty acid chain length of 12-22 carbon atoms is located at the sn-1 position.

[0069] In some preferred embodiments, the necessary component shown in i) includes at least LPE (18:2(9Z,12Z) / 0:0). This invention has found that the combination of LPE (18:2(9Z,12Z) / 0:0) and phosphatidylserine can exert a synergistic effect in assisting the improvement of memory impairment and / or the decline in abilities associated with memory impairment.

[0070] In some embodiments, lysophosphatidylethanolamine and phosphatidylserine, with fatty acid chains of 12-22 carbon atoms in length, are the main active ingredients of the nutritional composition. That is, the nutritional composition of the present invention mainly relies on the lysophosphatidylethanolamine and phosphatidylserine, which contain fatty acid chains of 12-22 carbon atoms in length, to exert specific physiological activities, such as assisting in improving memory impairment and / or the decline in abilities associated with memory impairment. In other words, in some embodiments, the active ingredient of the nutritional composition (the ingredient that exerts specific physiological activities, i.e., the ingredient that assists in improving memory impairment and / or the decline in abilities associated with memory impairment) is composed of lysophosphatidylethanolamine and phosphatidylserine, with fatty acid chains of 12-22 carbon atoms in length.

[0071] In some specific embodiments, the active ingredients of the nutritional composition include, or consist of, lysophosphatidylethanolamine and phosphatidylserine, a fatty acid chain of 18 carbon atoms linked at the sn-1 position.

[0072] In some preferred embodiments, the active ingredient of the nutritional composition comprises, or is composed of, lysophosphatidylethanolamine and phosphatidylserine, an unsaturated fatty acid chain of 18 carbon atoms linked at the sn-1 position.

[0073] In some preferred embodiments, the active ingredient of the nutritional composition (the ingredient that performs a specific physiological function, i.e., the ingredient that helps improve memory impairment and / or memory impairment-related decline in ability) comprises LPE (18:2(9Z,12Z) / 0:0) and phosphatidylserine, or is composed of the same.

[0074] In some embodiments, the nutritional composition comprises an active ingredient (a component that performs a specific physiological function, i.e., a component that helps improve memory impairment and / or the decline in abilities associated with memory impairment) and an inactive ingredient (a substance that does not help improve memory impairment and / or the decline in abilities associated with memory impairment, or at least does not exhibit synergistic effects with LPE (18:2(9Z,12Z) / 0:0) or phosphatidylserine). Exemplarily, the inactive ingredient may be other nutrients, any food-acceptable excipient, and / or substances that are generated during the production or acquisition of the active ingredient and cannot be effectively separated from the active ingredient or do not require separation. In some embodiments, the nutritional composition consists of the active ingredient and the inactive ingredient.

[0075] In some embodiments, in the nutritional composition, the mass ratio of the essential component shown in i) to the essential component shown in ii) is 1:(0.1-2000), for example, it can be 1:0.1, 1:0.5, 1:1, 1:2, 1:3, 1:3.5, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:11, 1:12, 1:13, 1:14, 1:15, 1:16, 1:17, 1:18, 1:19, 1:20, 1:21, 1:22, 1:23, 1:24, 1:2 4.5, 1:25, 1:26, 1:27, 1:28, 1:29, 1:30, 1:31, 1:32, 1:33, 1:34, 1:35, 1:36, 1:37, 1:38, 1:39, 1:40, 1:41, 1:42, 1:43, 1:44, 1:45, 1:46, 1:47, 1:48, 1:49, 1:50, 1:55, 1:60, 1:65, 1:70, 1:75, 1:80, 1:85, 1:90, 1:95, 1:100, 1:110, 1:1 20, 1:130, 1:140, 1:150, 1:160, 1:170, 1:180, 1:190, 1:196, 1:200, 1:210, 1:220, 1:224, 1:230, 1:240, 1:250, 1:260, 1:270, 1:280, 1:290, 1:300, 1:400, 1:500, 1:600, 1:700, 1:800, 1:900, 1:1000, 1:1100, 1:1200, 1:1300, 1:1400 The ratios are 1:1500, 1:1550, 1:1570, 1:1600, 1:1700, 1:1800, 1:1900, 1:2000, etc.; preferably, the mass ratio of the two is 1:(0.5-1600); more preferably, the mass ratio of the two is 1:(0.5-300); even more preferably, the mass ratio of the two is 1:(2-200); further preferably, the mass ratio of the two is 1:(20-30); preferably, the above ratio is the mass ratio of LPE (18:2(9Z,12Z) / 0:0) to phosphatidylserine.

[0076] The present invention does not impose any particular limitation on the form of the nutritional composition; typically, it can be a liquid or a solid. From the perspective of ease of production, transportation, storage, and use, the nutritional composition of the present invention is preferably a powdered solid.

[0077] (Uses of the nutritional composition)

[0078] This invention provides the use of the above-mentioned nutritional composition to assist in improving memory impairment and / or memory impairment accompanied by decreased abilities. In some embodiments, the assistance in improving memory impairment and / or memory impairment accompanied by decreased abilities is not for the purpose of preventing or treating disease, and the memory impairment and memory impairment accompanied by decreased abilities do not reach the level of disease; rather, the memory impairment is closer to a decline or reduction in memory function. Therefore, this invention provides the non-therapeutic use of the above-mentioned nutritional composition to assist in improving memory impairment and / or memory impairment accompanied by decreased abilities. Based on this, this invention also provides the use of the above-mentioned nutritional composition in the preparation of products that assist in improving memory impairment and / or memory impairment accompanied by decreased abilities.

[0079] In some embodiments, the present invention provides the use of the above-described nutritional composition in the preparation of products that help improve memory impairment and memory impairment-related decline in abilities.

[0080] In some implementations, the memory impairment accompanied by a decline in abilities includes one or both of behavioral and cognitive decline.

[0081] In some specific implementations, the decline in behavioral abilities associated with memory impairment includes a decline in motor abilities associated with memory impairment.

[0082] Based on this, the present invention also provides the use of the above-mentioned nutritional composition in the preparation of products that have the effect of improving the function of the cholinergic system.

[0083] In some embodiments, the improvement of cholinergic system function includes reducing the level of neurotransmitter-degrading enzymes; preferably, the neurotransmitter-degrading enzymes include acetylcholinesterase.

[0084] In some specific implementations, the improvement of cholinergic system function includes inhibiting acetylcholinesterase activity.

[0085] The present invention does not specifically limit the products containing the above-mentioned nutritional composition or products that can be prepared using the above-mentioned nutritional composition; for example, they can be food products.

[0086] In some implementation schemes, the food is designated as food for teenagers, young adults, or middle-aged and elderly people.

[0087] In some embodiments, the food product of this invention is a confectionery, such as hard candy, gel candy, shortbread candy, compressed candy, and aerated candy. In some embodiments, the food product of this invention is a beverage, such as carbonated beverages, tea beverages, coffee beverages, fruit and vegetable juice beverages, and lactic acid bacteria beverages. In some embodiments, the food product of this invention is a dairy product, such as milk powder, cheese, fermented milk, and liquid milk. In some embodiments, the food product of this invention is a baked product, such as bread, cakes, and biscuits. In some embodiments, the food product of this invention is a dietary supplement, such as hard capsules, soft capsules, tablets, oral liquids, pills, granules, and powders.

[0088] In some embodiments, the food described in this invention is in the form of a liquid or a solid under normal temperature conditions.

[0089] In some embodiments, in the food described in this invention, the mass ratio of the necessary component shown in i) to the necessary component shown in ii) can be 1:(0.1-2000); preferably, the mass ratio can be 1:(0.5-1600); more preferably, the mass ratio can be 1:(0.5-300); even more preferably, the mass ratio can be 1:(2-200); further preferably, the mass ratio can be 1:(20-30); preferably, the above ratio is the mass ratio of LPE (18:2(9Z,12Z) / 0:0) to phosphatidylserine.

[0090] This invention does not impose any specific absolute limits on the content of lysophosphatidylethanolamine, LPE (18:2(9Z,12Z) / 0:0) and phosphatidylserine in food, as long as the requirements of local food-related laws and regulations are met.

[0091] In some embodiments, the content of LPE (18:2(9Z,12Z) / 0:0) in the food, based on the total dry matter content of the food, can be 0.1-1000 mg / 100g, preferably 0.5-500 mg / 100g, more preferably 1-100 mg / 100g; the content of phosphatidylserine can be 10-1200 mg / 100g, preferably 30-900 mg / 100g, more preferably 50-600 mg / 100g.

[0092] In addition to the components described above in the nutritional composition, the food may also contain other ingredients, such as common food ingredients like proteins / amino acids, carbohydrates, fats, vitamins, and minerals.

[0093] In addition, 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.

[0094] 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; 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.

[0095] Animal dairy product ingredients can include fresh milk from mammals such as cows, sheep, and camels, 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.

[0096] Examples of animal meat product ingredients include pork, beef, mutton, seafood, and poultry.

[0097] Examples of functional additives include vitamin supplements (such as vitamin A, beta-carotene, vitamin D3, vitamin E, vitamin K1, vitamin B1, vitamin B2, vitamin B6, and vitamin B1). 12 Supplements include: Vitamin C, pantothenic acid, folic acid, niacin, biotin, etc.; mineral supplements (e.g., calcium, iron, copper, manganese, zinc, magnesium, fluorine, sodium, potassium, selenium, iodine, etc.); nucleotide supplements (e.g., disodium 5'-cytidine, disodium 5'-uridine, adenosine monophosphate, disodium 5'-guanylate, disodium 5'-inosine, etc.); dietary fiber (e.g., inulin, konjac flour, galactooligosaccharides, fructooligosaccharides, isomaltooligosaccharides, soybean polysaccharides, cyclodextrin, resistant dextrin, soybean fiber, etc.); and polyunsaturated fatty acid supplements (e.g., docosahexaenoic acid, eicosapentaenoic acid, eicosapentaenoic acid, etc.).

[0098] 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.

[0099] Example

[0100] 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 in the examples, conventional conditions or conditions recommended by the manufacturer are followed. Reagents or instruments whose manufacturers are not specified are all commercially available conventional products.

[0101] The experimental equipment used in the experimental examples of this invention includes: a dissecting microscope (SZX7, OLYMPUS, Japan), a CCD camera (VertA1, Shanghai Tusen Vision Technology Co., Ltd.), a motorized focusing continuous zoom fluorescence microscope (AZ100, Nikon, Japan), a precision electronic balance (CP214, OHAUS, USA), a behavior analyzer (Zebra Lab 3.22.3.31, ViewPoint, France), a multi-functional microplate reader (SPARK, TECAN, Austria), a high-speed refrigerated centrifuge (Heraeus Fresco 17, Thermo Fisher, Germany), a UV-Vis spectrophotometer (Nanodrop 2000, Thermo, Austria), a microplate mini centrifuge (BE-6100, Haimen Qilinbei Instrument Manufacturing Co., Ltd.), a fully automated sample grinder (JXFSTPRP-24L, Shanghai Jingxin Experimental Equipment Technology Department), 6-well plates (Belamber Biotechnology Co., Ltd.), and 96-well plates (Nest). Biotech) and black 96 microplate (batch number 34519060, Costa, USA).

[0102] The experimental materials and reagents used in the experimental examples of this invention include: LPE18:2 (LPE(18:2(9Z,12Z) / 0:0)) provided by Heilongjiang Feihe Dairy Co., Ltd.; phosphatidylserine (PS) provided by International Flavors & Fragrances (IFF); positive control: donepezil hydrochloride; dimethyl sulfoxide (DMSO, batch number I2229063, Shanghai Aladdin Biochemical Technology Co., Ltd.); aluminum chloride hexahydrate (batch number C1628001, Shanghai Aladdin Biochemical Technology Co., Ltd.); BCA protein concentration assay kit (batch number AR1189, Boster Biological Engineering Co., Ltd.); acetylcholinesterase assay kit (batch number 3040802, AAT Bioquest, USA).

[0103] The experimental animals used in the experimental examples of this invention are wild-type AB strain zebrafish.

[0104] In the experimental examples of this invention, data processing was performed using SPSS 26.0 software for statistical analysis. Data were described by mean ± standard error (mean ± SE), and p < 0.05 was used as the significance level.

[0105] Experimental Example 1: Determination of the Maximum Tolerable Concentration of Nutrients

[0106] This experiment tested the maximum tolerable concentration (MTC) of two nutrients in zebrafish. The specific steps are as follows:

[0107] Zebrafish strain: Wild-type AB strain zebrafish, 30 fish in each experimental group, were incubated in an incubator at 28℃.

[0108] Experimental groups: Two samples were set up (LPE18:2 and PS), with 8 detection concentrations for LPE18:2 and 5 detection concentrations for PS; at the same time, one normal control group (normal zebrafish without any treatment or intervention) and one model control group (treated with 38.6 μg / mL aluminum chloride) were set up.

[0109] Experimental Methods: Wild-type AB strain zebrafish, 4 days post-fertilization (4 dpf), were randomly selected and placed in 6-well plates, with 30 zebrafish treated per well (each experimental group). Water-soluble samples were administered, and a normal control group was also included. The volume per well was 3 mL. After treatment at 28℃ for 1 day, the MTC of each sample on zebrafish was measured.

[0110] Experimental Results: As shown in Table 1, when the concentration of LPE18:2 was gradually increased from 0.156 μg / mL to 10 μg / mL, the zebrafish condition was similar to that of the model control group; when the concentration was further increased to 20 μg / mL, the zebrafish began to die; therefore, the MTC of LPE18:2 in the subsequent experiment on improving memory impairment was 10 μg / mL. For PS, when the concentration was increased from 125 μg / mL to 500 μg / mL, the zebrafish condition was similar to that of the model control group; when the concentration was further increased to 1000 μg / mL, the zebrafish condition was significantly worse than that of the model control group; therefore, the MTC of PS in the subsequent experiment on improving memory impairment was 500 μg / mL.

[0111] Table 1. Results of the concentration exploration experiment on the efficacy of the sample in improving memory impairment (n=30)

[0112]

[0113] Experiment Example 2: Dose-response assessment of the effect of nutrient intervention on the improvement of behavioral abilities in zebrafish

[0114] Excessive intake of aluminum chloride can lead to abnormal animal behavior, damage cholinergic nerve function, and increase the production of amyloid protein, ultimately inducing memory loss and decreased learning ability. Therefore, this study used an aluminum chloride-induced zebrafish memory impairment model, and used the zebrafish's behavioral ability (i.e., total movement distance) as an indicator to evaluate whether the two nutrients have an effect on improving memory.

[0115] Zebrafish strain: Wild-type AB strain zebrafish, 30 fish in each experimental group, were incubated in an incubator at 28℃.

[0116] Experimental groups: LPE18:2 and PS each had 5 concentrations (MTC group, 1 / 2MTC, 1 / 4MTC, 1 / 8MTC, 1 / 16MTC); in addition, there was 1 normal control group, 1 model control group and 1 positive control group (donepezil hydrochloride), for a total of 13 groups.

[0117] Experimental Methods: Wild-type AB strain zebrafish (4 dpf) were randomly selected and placed in 6-well plates, with 30 fish per well (each experimental group). Samples were administered via water-soluble solution. The positive control group received 3.33 μg / mL donepezil hydrochloride. A normal control group and a model control group were also included, with a volume of 3 mL per well. Except for the normal control group, all other groups received water-soluble aluminum chloride hexahydrate to establish a zebrafish memory impairment model. After treatment at 28℃ for one day, 10 zebrafish were randomly selected from each experimental group, and their total movement distance within 1 hour was measured using a behavior analyzer. Statistical analysis of this indicator was used to evaluate the improvement effect of the samples on behavioral abilities.

[0118] Experimental Results: As shown in Table 2, the average total movement distance of zebrafish in the normal control group was 5512.83 mm; after treatment with aluminum chloride, the total movement distance of the model control group significantly decreased to 2141.08 mm. After donepezil intervention, the total movement distance of the positive control group increased to 3532.42 mm. Statistical analysis showed that the positive control group's movement distance was significantly higher than that of the model control group, indicating that donepezil intervention can effectively restore the behavioral abilities of zebrafish.

[0119] At a maximum concentration of 10 μg / mL and five concentrations that were subsequently halved, LPE18:2 increased the total movement distance of zebrafish to varying degrees, exhibiting a dose-dependent effect. Significant difference analysis showed that the total movement distance at all five concentrations was significantly higher than that at the model control group.

[0120] At the maximum concentration of 250 μg / mL and five concentrations that were subsequently halved, PS increased the total movement distance of zebrafish to varying degrees, showing a dose-dependent effect, but the overall increase was slightly lower than that of LPE18:2. Significance analysis showed that PS at the two lowest concentrations was not significantly different from the model control group, but when the concentration reached 62.5 μg / mL and above, the total movement distance was significantly higher than that of the model control group.

[0121] The results indicate that LPE18:2 can significantly enhance the total motility of zebrafish induced by aluminum chloride in the concentration range of 0.625-10 μg / mL; PS can also significantly enhance the total motility of zebrafish induced by aluminum chloride in the concentration range of 62.5-250 μg / mL.

[0122] Table 2. Effects of different doses of the two nutrients on the total distance traveled by zebrafish

[0123]

[0124] Experiment Example 3: Effects of two nutrients, alone or in combination, on the total distance traveled by zebrafish

[0125] Wild-type AB strain zebrafish (4 dpf) were randomly selected and placed in 6-well plates, 30 fish per well. A normal control group, a model control group, a positive control group, and sample treatment groups (including Comparative Examples 1-6 and Examples 1-9) were set up. The zebrafish in the normal control group were cultured routinely without any treatment or intervention; all other groups were treated with 38.6 μg / mL aluminum chloride. Specifically, the model control group received no intervention after aluminum chloride treatment; the positive control group received aluminum chloride treatment followed by donepezil hydrochloride intervention at 3.33 μg / mL; Comparative Examples 1-3 received aluminum chloride treatment followed by LPE18:2 intervention at 0.156 μg / mL, 1.25 μg / mL, and 10 μg / mL, respectively; Comparative Examples 4-6 received aluminum chloride treatment followed by PS intervention at 5 μg / mL, 35 μg / mL, and 245 μg / mL, respectively; and Examples 1-9 received aluminum chloride treatment followed by combinations of LPE18:2 and PS in different ratios (1:0.5 to 1:1570). The specific experimental group settings are shown in Table 3.

[0126] Table 3. Experimental Intervention Design

[0127]

[0128] To verify the synergistic effect of LPE18:2 and PS in improving the behavioral abilities of zebrafish, this study set up different combinations of the two to analyze the effects of individual and combined nutrient interventions on the total movement distance. The experimental results are shown in Table 4, and the significance analysis of differences between groups is shown in Table 5.

[0129] Table 4 shows that after LPE18:2 intervention at low, medium, and high doses (Comparative Examples 1-3), the total movement distance of zebrafish was increased to varying degrees compared with the model control group. Significant difference analysis showed that the total movement distance after intervention at low dose in Comparative Example 1 was not significantly different from the model control group (p>0.05), while the total movement distance after intervention at medium and high doses was significantly higher than the model control group (p<0.0001). Comparative Examples 4-6 show the changes in total movement distance after intervention with PS alone. Although there was also some improvement compared with the model control group, significant difference analysis showed that only the total movement distance after intervention at high dose in Comparative Example 6 was significantly higher than the model control group (p<0.0001), while the total movement distance after intervention at low dose in Comparative Example 4 and medium dose in Comparative Example 5 was not significantly different from the model control group (p>0.05). These results indicate that intervention with either nutrient alone can improve the behavioral ability of zebrafish to some extent, with LPE18:2 showing a better effect than PS.

[0130] Examples 1-9 demonstrate the effect of combining LPE18:2 and PS in different proportions to form compositions on the total movement distance of zebrafish. The results showed that the total movement distance after composition intervention was superior to that of either nutrient alone, with longer total movement distances. Significant difference analysis indicated that the total movement distance in all nine examples was significantly higher than that in the model control group (p<0.0001), and also significantly higher than that in the six comparative examples (p values ​​are detailed in Table 5). This indicates that the combined use of the two nutrients has a synergistic effect on improving the total movement ability of zebrafish.

[0131] Further analysis revealed that the total movement distance in all nine examples was greater than the sum of the effects of the two nutrients alone at the same concentration, confirming that the combination of LPE18:2 and PS has a synergistic effect on increasing the total movement distance of zebrafish.

[0132] Table 4. Effects of nutrient monomer and combination interventions on the total distance traveled by zebrafish

[0133]

[0134] Table 5. Significance analysis of intergroup differences in the effects of different nutrient interventions on the total distance traveled by zebrafish.

[0135]

[0136]

[0137] Experiment Example 4: The effects of using two nutrients alone or in combination on improving cognitive abilities in zebrafish

[0138] Zebrafish strain: Wild-type AB strain zebrafish, 30 fish in each experimental group, were incubated in an incubator at 28℃.

[0139] Experimental groups: 15 groups were set up for intervention with LPE18:2 and PS monomer and their different ratios. At the same time, there was 1 normal control group, 1 model control group and 1 positive control group (donepezil hydrochloride).

[0140] Experimental Methods: Wild-type AB strain zebrafish, 5 days post-fertilization (5 dpf), were randomly selected and placed in beakers, with 30 fish per beaker (each experimental group). The samples were administered in water-soluble form. The positive control group received 3.33 μg / mL donepezil hydrochloride, and a normal control group was also included. Each beaker had a volume of 20 mL. After treatment at 28℃ for 1 day, 5 zebrafish were randomly selected from each experimental group and placed in a cross-shaped module. This module was divided into four regions: yellow, blue, red, and green, with 6 modules per group. Data were collected using a behavior analyzer, and the percentage (%) of the total movement distance of the zebrafish within the blue region relative to the total movement distance of the entire region within 10 minutes was analyzed. The statistical analysis results of this indicator were used to evaluate the efficacy of the sample in improving cognitive abilities.

[0141] Memory is the foundation of cognition and a component of cognition. Direct detection of the proportion of the total movement distance in the blue area to the total movement distance in the entire area reflects the zebrafish's own color cognition ability, which includes the scope of memory. Moreover, existing literature shows that the color-enhanced conditional position preference (CPP) test is a new type of learning and memory test, which is based on the zebrafish's natural preference for specific colors. This preference may lead to changes in visual discrimination learning, memory and decision-making abilities (Li X, Li X, Li YX, Zhang Y, Chen D, Sun MZ, Zhao X, Chen DY, Feng XZ. The Difference between Anxiolytic and Anxiogenic Effects Induced by Acute and Chronic Alcohol Exposure and Changes in Associative Learning and Memory Based on Color Preference and the Cause of Parkinson-Like Behaviors in Zebrafish. PLoS One. 2015 Nov 11;10(11):e0141134.).

[0142] The experimental results are shown in Table 6, and the significance analysis of differences between groups is shown in Table 7.

[0143] Table 6 shows that the average distance traveled by zebrafish in the blue area of ​​the cross maze in the normal control group was approximately 56.96%. However, after treatment with aluminum chloride, the proportion of this distance traveled by the model control group in this area significantly decreased to 25.66%, indicating that aluminum chloride treatment caused severe cognitive impairment in the zebrafish. In the positive control group, after intervention with donepezil hydrochloride, the proportion of the distance traveled in the blue area rebounded to 53.07%, suggesting that the cognitive function of the zebrafish improved.

[0144] Comparative Examples 1-3 illustrate the percentage of movement distance in the blue area of ​​the cross maze induced by low, medium, and high doses of LPE18:2 with aluminum chloride. The results showed that all three doses increased the distance movement distance compared to the model control group to varying degrees. However, significance analysis indicated that the percentage of movement distance in the blue area after low-dose intervention (Comparative Example 1) was not significantly different from the model control group (p>0.05), while the percentages after medium and high-dose interventions were significantly higher than those after the model control group (p values ​​are shown in Table 7).

[0145] Comparative Examples 4-6 illustrate the percentage of movement distance in the blue area of ​​the cross maze induced by low, medium, and high doses of PS intervention with aluminum chloride. The results showed that although all interventions improved to varying degrees compared to the model control group, significance analysis indicated that the percentage of movement distance in the blue area was not significantly different between the low-dose intervention (Comparative Example 4) and the model control group, while the medium and high-dose interventions (Comparative Examples 5 and 6) significantly improved the percentage of movement distance compared to the model control group (p-values ​​are shown in Table 7). These results suggest that interventions with either nutrient at certain doses can also enhance the cognitive abilities of zebrafish.

[0146] Examples 1-9 demonstrate the effect of combining LPE18:2 and PS in different proportions to form compositions on the proportion of movement distance in the blue region of zebrafish. The results showed that the combined intervention of the two nutrients resulted in a higher proportion of movement distance in the blue region compared to either nutrient alone. Significant difference analysis showed that the proportion of movement distance in the blue region in all nine examples was significantly higher than that in the model control group (p<0.0001), and also significantly higher than that in the six comparative examples (p values ​​are shown in Table 7). This indicates that the combined use of the two nutrients has a synergistic effect on improving the cognitive ability of zebrafish.

[0147] Further analysis revealed that the effects of all nine examples were greater than the sum of the effects of the two nutrients alone at the same concentration, confirming that the combination of LPE18:2 and PS has a synergistic effect on increasing the proportion of zebrafish moving in the blue area.

[0148] Table 6. Effects of nutrient monomer and combination interventions on the proportion of movement in the blue area of ​​zebrafish in the cross maze.

[0149]

[0150] Table 7. Significant differences among zebrafish groups in the proportion of movement within the blue area of ​​the cross maze.

[0151]

[0152]

[0153] Experiment Example 5: Effects of two nutrients, alone or in combination, on the activity of acetylcholinesterase in zebrafish

[0154] The cholinergic system (centered on acetylcholine) is a key regulatory system for memory formation and consolidation. Damage to this system directly leads to difficulties in memory encoding, consolidation impairment, and decreased hippocampal plasticity, and is highly correlated with memory disorders such as Alzheimer's disease. Cholinergic damage is closely related to acetylcholinesterase (AChE) activity: when acetylcholinesterase activity is too high, it accelerates the degradation of acetylcholine, directly impairing cholinergic system function and thus triggering memory and cognitive decline. Therefore, this study assessed the degree of damage to the cholinergic system and the effects of nutritional interventions on acetylcholinesterase fluorescence values ​​in zebrafish after modeling and different nutrient interventions.

[0155] Zebrafish strain: Wild-type AB strain zebrafish, 30 fish in each experimental group, were incubated in an incubator at 28℃.

[0156] Experimental groups: 15 groups were set up for intervention with LPE18:2 and PS monomer and their different ratios. At the same time, there was 1 normal control group, 1 model control group and 1 positive control group (donepezil hydrochloride).

[0157] Experimental Methods: Wild-type AB strain zebrafish (4 dpf) were randomly selected and placed in 6-well plates, with 30 fish per well (each experimental group). Samples were administered via water-soluble solution. The positive control group received 3.33 μg / mL donepezil hydrochloride. A normal control group and a model control group were also included, with a volume of 3 mL per well. Except for the normal control group, all other groups received water-soluble aluminum chloride to establish a zebrafish memory impairment model. After treatment at 28℃ for 48 h, data were collected using an acetylcholinesterase assay kit and a multi-functional microplate reader. The fluorescence value of acetylcholinesterase in zebrafish was analyzed, and the statistical analysis results of this index were used to evaluate the inhibitory efficacy of the samples on acetylcholinesterase.

[0158] The experimental results are shown in Table 8, and the significance analysis of differences between groups is shown in Table 9.

[0159] As shown in Table 8, the average fluorescence value of acetylcholinesterase (AChE) in the normal control group of zebrafish was approximately 5002.00. After treatment with aluminum chloride, the AChE fluorescence value in the model control group significantly increased to 9194.90, indicating that aluminum chloride treatment caused severe damage to the cholinergic system in zebrafish. After intervention with donepezil hydrochloride, the AChE fluorescence value decreased to 5677.60, suggesting that the function of the cholinergic system was restored.

[0160] Comparative Examples 1-3 demonstrate the in vivo AChE fluorescence levels in zebrafish induced by aluminum chloride after intervention with LPE18:2 at low, medium, and high doses. The results showed that the AChE fluorescence values ​​under all three doses were lower than those under the model control group to varying degrees. Statistical analysis indicated that the values ​​in all three comparative examples were significantly lower than those under the model control group (p values ​​are shown in Table 9).

[0161] Comparative Examples 4-6 demonstrate the in vivo AChE fluorescence levels in zebrafish after intervention with low, medium, and high doses of PS at aluminum chloride induction. The results showed that the AChE fluorescence values ​​at all three intervention doses were significantly lower than those in the model control group (p values ​​are shown in Table 9). These results indicate that intervention with either of the two nutrients alone can also have a certain effect in repairing cholinergic damage.

[0162] Examples 1-9 demonstrate the effect of combining LPE18:2 and PS in different ratios on AChE fluorescence levels in zebrafish. The results showed that the AChE fluorescence values ​​after intervention with the combined nutrients were lower than those after intervention with either nutrient alone, exhibiting significantly lower fluorescence values. Significant difference analysis showed that the AChE fluorescence values ​​in all nine examples were significantly lower than those in the model control group (p<0.0001), and significantly lower than those in the six comparative examples (p values ​​are shown in Table 9). This indicates that the combined use of the two nutrients has a synergistic effect on repairing cholinergic damage in zebrafish.

[0163] Further analysis revealed that the effects of all nine examples were greater than the simple sum of the effects of the two nutrients alone at the same concentration, confirming that the combination of LPE18:2 and PS has a synergistic effect on reducing AchE fluorescence values ​​in zebrafish.

[0164] Table 8. Effects of nutrient monomers and combinations on acetylcholinesterase activity in zebrafish

[0165]

[0166] Table 9. Analysis of significant differences in acetylcholinesterase activity among different groups of zebrafish

[0167]

[0168]

Claims

1. A nutritional composition, characterized in that, The nutritional composition comprises the following two essential components: i) Lysophosphatidylethanolamine; ii) Phosphatidylserine; Furthermore, in the nutritional composition, the mass ratio of the lysophosphatidylethanolamine to the phosphatidylserine is 1:(0.1-2000).

2. The nutritional composition according to claim 1, characterized in that, The fatty acid chain in the lysophosphatidylethanolamine contains between 12 and 22 carbon atoms.

3. The nutritional composition according to claim 1 or 2, characterized in that, The fatty acid chain in the lysophosphatidylethanolamine is located at the sn-1 position.

4. The nutritional composition according to any one of claims 1-3, characterized in that, The fatty acid chains in the lysophosphatidylethanolamine are unsaturated.

5. The nutritional composition according to any one of claims 1-4, characterized in that, The lysophosphatidylethanolamine is provided in the form of dairy products containing it and / or enzymatically hydrolyzed soybean lecithin.

6. Use of the nutritional composition according to any one of claims 1-5 in the preparation of products that help improve memory impairment and / or memory impairment accompanied by decreased abilities.

7. The use according to claim 6, characterized in that, The memory impairment accompanied by a decline in abilities includes one or both of the following: a decline in behavioral abilities and a decline in cognitive abilities.

8. The use of the nutritional composition according to any one of claims 1-5 in the preparation of a product having the effect of improving the function of the cholinergic system.

9. The use according to claim 8, characterized in that, The improvement of cholinergic system function includes reducing the level of neurotransmitter-degrading enzymes.

10. The use according to any one of claims 6-9, characterized in that, The product contains any one or more of the following ingredients: plant-based ingredients, animal dairy ingredients, animal meat ingredients, functional additives, and any acceptable excipients.

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