Use of a nutritional composition for enhancing immunity

Abstract

This invention provides an application of a nutritional composition for enhancing immunity. The nutritional composition of this invention comprises medium- and long-chain triglycerides (MLCT) and milk fat globule membrane (MFGM) in a mass ratio of 0.3:1 to 120:1. This nutritional composition can increase the proliferation of immune cells, and is used as a method for improving immunity.

Description

Technical Field

[0001] This invention relates to the field of food or pharmaceutical technology. Specifically, this invention relates to nutritional compositions, products comprising the same, and their use in the preparation of products for improving immunity. Background Technology

[0002] The immune system, as a key protective system of the body, plays a vital role in safeguarding life and health. It effectively identifies and eliminates pathogens that invade the body, while maintaining tolerance to its own tissues and preserving homeostasis. In recent years, influenced by factors such as dietary structure, environmental changes, lifestyle habits, mental stress, and medication use, immunodeficiency has gradually become a common adverse health condition. When the body is in a state of immunodeficiency, the immune system's function weakens, thereby increasing the risk of pathogen infection. Furthermore, immunodeficiency can also affect other functions of the immune system, such as clearing necrotic cells and monitoring malignant tumor cells. Impairment of these functions can lead to a series of health problems, such as upper respiratory tract infections, gastrointestinal infections, lethargy, fatigue, and may even increase the risk of developing tumors. Therefore, actively improving immunodeficiency is of great significance for maintaining public health (Parkin J, Cohen B. An overview of the immune system. Lancet. 2001 Jun 2;357(9270):1777-89.).

[0003] Most importantly, because infants' and young children's immune systems are not yet fully developed, their resistance and immunity are relatively weak, making them susceptible to infections from pathogens and viruses. The most direct manifestation of physiological immunodeficiency in infants and young children is their susceptibility to illness, such as various acute and chronic diseases like colds, fevers, coughs, asthma, vomiting, diarrhea, or constipation. Furthermore, physiological immunodeficiency in infants and young children often manifests as prolonged recovery times after illness, with prolonged illness courses and recurring episodes. Over time, this not only hinders the development and maturation of various organs in infants and young children but also has varying degrees of negative impact on their intellectual development and cognitive levels.

[0004] Medium- and long-chain triacylglycerols (MLCTs) have attracted widespread attention as a promising new type of structured lipid. The main structural feature of MLCTs is the simultaneous binding of medium-chain and long-chain fatty acids to a glycerol backbone. The fatty acid composition of MLCTs is closer to that of breast milk, which is beneficial for fat digestion and absorption, improves the absorption of lipid nutrients, inhibits the accumulation of body fat, and provides rapid and stable energy (Medium- and Long-Chain Triacylglycerol: Preparation, Health Benefits, and Food Utilization; Research Progress on Medium- and Long-Chain Triacylglycerols in Breast Milk). Furthermore, MLCTs possess different metabolic characteristics and physiological functions compared to physically mixed long-chain and medium-chain triacylglycerols.

[0005] Even with the same overall fatty acid composition in breast milk, medium- and long-chain triglycerides (MLCTs) exhibit different biological functions compared to physically mixed long-chain triglycerides (LCTs) / medium-chain triglycerides (MCTs). For example, mouse studies have shown that feeding mice with a formula lipid diet containing breast milk structural MLCTs (MLCTs) regulates thermogenesis, inhibits visceral fat accumulation, alters gut microbiota, and regulates lipid metabolism, compared to feeding mice with a formula lipid diet containing a physically mixed vegetable oil diet of LCT / MCTs with the same fatty acid composition (Novel Human Milk Fat Substitutes Based on Medium- and Long-Chain Triacylglycerol Regulate Thermogenesis, Lipid Metabolism, and Gut Microbiota Diversity in C57BL / 6J Mice). Currently, whether MLCTs, alone or synergistically with milk fat globule membranes, improve immunity requires further investigation.

[0006] Chinese patent application CN116019149B discloses a fat component for a special medical purpose formulation food and its preparation method. This fat component has a triglyceride structure with a specific MLCT composition, exhibiting higher digestibility and absorption, and improving the bioavailability of EPA and DHA. It helps improve the nutritional status of liver cancer patients during chemotherapy, provides immediate energy for postoperative liver cancer patients, reduces inflammatory responses, and enhances immunity.

[0007] Patent ZA202206364B discloses a yak milk formula milk powder with immune-regulating function. The formula milk powder with added milk fat globule membrane protein in a specific ratio is suitable for the physical and bone development of children aged 3-6 years. It is easy to digest and absorb. As a supplementary food for children's growth and development, it has excellent antiviral and antibacterial effects, reduces the incidence of intestinal diseases, and improves children's physical fitness.

[0008] Furthermore, the "Scientific Consensus on Milk Fat Globule Membrane and Its Ingredients" published by the Chinese Institute of Food Science and Technology indicates that when the intake of milk fat globule membrane protein is 0.42~4.2g / d, infant formula can improve infant immunity and reduce the incidence of inflammation and the number of times patients need to visit a doctor.

[0009] There is still a need in this field for nutritional compositions that improve immunity. Summary of the Invention

[0010] The purpose of this invention is to provide a nutritional composition for improving immunity, comprising medium-long chain triglycerides (MLCT) and milk fat globule membranes (MFGM), which have the effect of improving immunity. This invention also discovers that MLCT and MFGM have a synergistic effect in enhancing immunity, particularly in improving the reduction of T cell count, macrophage count, and neutrophil count in individuals with low immunity.

[0011] In a first aspect, a nutritional composition is provided for use for non-therapeutic purposes to enhance immunity, wherein the nutritional composition comprises medium- and long-chain triglycerides (MLCT) and milk fat globule membranes (MFGM). In one embodiment, the mass ratio of MLCT to MFGM is from 0.3:1 to 120:1. In a preferred embodiment, the mass ratio of MLCT to MFGM is from 0.3:1 to 28:1. In a preferred embodiment, the mass ratio of MLCT to MFGM is from 20:1 to 28:1. In a preferred embodiment, the mass ratio of MLCT to MFGM is from 0.3:1 to 24:1.

[0012] In one embodiment, the enhanced immunity includes enhancing systemic immunity. In another embodiment, the enhanced immunity includes restoring reduced T cell numbers and / or reduced macrophage numbers and / or reduced neutrophil numbers in subjects with low immunity.

[0013] In one implementation, the subject with low immunity is either a subject with primary immunodeficiency or a subject with secondary immunodeficiency.

[0014] In a second aspect, the use of a nutritional composition in the preparation of a product for enhancing immunity is provided, wherein the nutritional composition comprises medium- and long-chain triglycerides (MLCT) and milk fat globule membranes (MFGM). In one embodiment, the mass ratio of MLCT to MFGM is from 0.3:1 to 120:1. In a preferred embodiment, the mass ratio of MLCT to MFGM is from 0.3:1 to 28:1. In a preferred embodiment, the mass ratio of MLCT to MFGM is from 20:1 to 28:1. In a preferred embodiment, the mass ratio of MLCT to MFGM is from 0.3:1 to 24:1.

[0015] In one embodiment, the enhanced immunity includes enhancing systemic immunity. In another embodiment, the enhanced immunity includes restoring reduced T cell numbers and / or reduced macrophage numbers and / or reduced neutrophil numbers in subjects with low immunity.

[0016] In one implementation, the subject with low immunity is either a subject with primary immunodeficiency or a subject with secondary immunodeficiency.

[0017] In one embodiment, the product is a pharmaceutical or food product.

[0018] In one embodiment, the food includes ordinary food, health food, special medical food, or infant formula.

[0019] In one embodiment, the food includes dairy products, health foods, fermented foods, beverages, bread, biscuits, and confectionery.

[0020] In one embodiment, the food is infant formula, children's formula, adolescent formula, formula for pregnant women, or formula for the middle-aged and elderly.

[0021] In the third aspect, methods for enhancing the immunity of subjects are provided, which include administering the nutritional compositions or products described herein to the subjects.

[0022] In one implementation, the subject is either a healthy subject or a subject with low immunity.

[0023] In one implementation, enhancing immunity includes restoring reduced T cell numbers and / or reduced macrophage numbers and / or reduced neutrophil numbers in subjects with low immunity, for example, restoring T cell numbers and / or macrophage numbers and / or neutrophil numbers to those in normal subjects.

[0024] In one embodiment, the subject with low immunity is either a subject with primary immunodeficiency or a subject with secondary immunodeficiency. In another embodiment, the subject is a human being.

[0025] In a fourth aspect, the use of a nutritional composition in the preparation of a medicament for treating or preventing immunodeficiency is provided, wherein the nutritional composition comprises medium- and long-chain fatty acid triglycerides (MLCT) and milk fat globule membranes (MFGM). In one embodiment, the mass ratio of MLCT to MFGM is from 0.3:1 to 120:1. In a preferred embodiment, the mass ratio of MLCT to MFGM is from 0.3:1 to 28:1. In a preferred embodiment, the mass ratio of MLCT to MFGM is from 20:1 to 28:1. In a preferred embodiment, the mass ratio of MLCT to MFGM is from 0.3:1 to 24:1.

[0026] In one embodiment, the weakened immunity is caused by primary or secondary immunodeficiency.

[0027] In a sixth aspect, methods for treating or preventing immunodeficiency in subjects are provided, comprising administering the nutritional composition described herein to the subjects.

[0028] In one embodiment, the weakened immunity is caused by primary or secondary immunodeficiency.

[0029] The beneficial effects of this invention include: when MLCT and MFGM are used in combination at a mass ratio of 0.3:1 to 120:1, preferably 0.3:1 to 24:1, there is a synergistic effect between the two in restoring reduced T cell and / or reduced macrophage and / or reduced neutrophil numbers in subjects with low immunity. Compositions containing MLCT and MFGM at a mass ratio of 0.3:1 to 120:1 can be used to prepare immune-enhancing foods or pharmaceuticals. Attached Figure Description

[0030] Figure 1 Typical fluorescence intensity of zebrafish T cells after sample treatment.

[0031] Figure 2 Typical fluorescence intensity of zebrafish macrophages after sample processing. Note: The red dashed line indicates the analysis area.

[0032] Figure 3 Typical neutrophil count in zebrafish after sample processing. Note: The yellow dashed line represents the analysis area. Detailed Implementation

[0033] The following definitions are provided to enable those skilled in the art to understand the invention. Unless otherwise defined, all 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 pertains. Preferred materials and methods are described herein, but any methods and materials similar to or equivalent to those described herein may be used in the practice of testing the invention. It should also be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting.

[0034] Terminology Definition

[0035] Unless otherwise indicated or defined, all terms used have their ordinary meaning in the art as would be understood by those skilled in the art. Furthermore, unless otherwise stated, all methods, steps, techniques, and operations not specifically detailed herein can and have been performed in a manner known per se as would be understood by those skilled in the art.

[0036] As used herein, “immunity” or “immunity” may refer interchangeably to systemic immunity. Systemic immunity refers to the continuous generation of immune cells by the body through central immune organs (bone marrow, thymus) and their release into the systemic bloodstream and lymphatic system, thereby forming a unified defense network covering all tissues and organs of the body. In some embodiments, the compositions described herein can enhance systemic immunity.

[0037] As used in this article, the main structural feature of medium- and long-chain triacylglycerols (MLCTs) is that a glycerol backbone is simultaneously bound to both medium-chain and long-chain fatty acids. The fatty acid composition of MLCTs is closer to that of breast milk, which is beneficial for fat digestion and absorption, improves the absorption of lipid nutrients, inhibits the accumulation of body fat, and provides rapid and stable energy (Medium- and Long-Chain Triacylglycerol: Preparation, HealthBenefits, and Food Utilization; Research Progress on Medium- and Long-Chain Triacylglycerols in Breast Milk). Furthermore, MLCTs possess different metabolic characteristics and physiological functions compared to physically mixed long-chain and medium-chain triacylglycerols.

[0038] As used herein, the term "milk fat globule membrane" or "MFGM" is a complex biomembrane structure found in breast milk. The milk fat globule membrane is a complex three-layered phospholipid protein membrane encapsulating the surface of milk fat droplets, composed of polar lipids, cholesterol, and proteins. The source of the milk fat globule membrane for this invention is not particularly limited in principle and can generally be obtained by extraction from animal milk or its products. In some preferred embodiments, such animal milk or its products can be cow's milk, sheep's milk, camel's milk, horse's milk, or dairy products based on them (e.g., cheese), etc. More preferably, it can be extracted from cow's milk, including bovine colostrum or regular bovine milk. The method for extracting MFGM from the above-mentioned animal milk or its products is not particularly limited in this invention. For example, it can be carried out using an acidification precipitation-centrifugation-isoelectric point enrichment-drying method, or it can be separated using existing membrane filtration methods. Additionally, MFGM can also be obtained from commercially available products, including milk fat globule membrane whey protein powder and milk fat globule membrane milk protein powder. Milk fat globule membrane whey protein powder refers to a powdered product containing milk fat globule membranes, made from raw milk or whey through processes such as separation, concentration, and drying. Milk fat globule membrane whey protein powder refers to a powdered product containing milk fat globule membranes, made from raw milk or cream through processes such as separation, concentration, and drying. Commercial sources of MFGM used in this invention include Lacprodan® MFGM-10, Lacprodan® PL-20, Cor-Power® SM2, lipid-rich MFGM fraction, or buttermilk powder concentrates such as BPC50, BPC60, G600, PC700, Hilmar Cor-Power® WPC7500MEGM ENRICHED WPC, etc.

[0039] As used herein, the term "enhancing immunity" refers to regulating and improving the body's immune function. In this context, enhancing immunity can refer to enhancing the activity of immune cells, such as increasing the phagocytic or killing capacity of macrophages, neutrophils, natural killer cells (NK cells), and T lymphocytes. T cells, macrophages, and neutrophils are the core forces of the immune system; their adequate numbers and normal function are crucial for maintaining strong immunity. The nutritional compositions or products described herein may be adjuncts to enhancing immunity or contribute to enhancing immunity. In some embodiments, enhancing immunity may involve restoring reduced T cell and / or reduced macrophage and / or reduced neutrophil numbers in subjects with low immunity, for example, restoring T cell and / or macrophage and / or neutrophil numbers to those in normal subjects.

[0040] As used herein, the term "non-therapeutic purpose" has its conventional meaning in the art, including, for example, nutritional and / or health purposes, such as for the preparation of food products like general foods, functional foods, or health foods.

[0041] As used herein, the terms “low immunity” or “immunodeficiency” are used interchangeably and can refer to an absolute count of key immune cells (such as T cells, macrophages, and neutrophils) in peripheral blood that is below the lower limit of the normal reference range. Subjects with “low immunity” or “immunodeficiency” can be either those with primary immunodeficiency or secondary immunodeficiency. Primary immunodeficiency is an incomplete immune system function caused by genetic factors or congenital developmental abnormalities, and is usually detected in childhood. Secondary immunodeficiency is an impairment of the immune system due to acquired diseases, medications, or physiological conditions. Examples of secondary immunodeficiency include impaired immune system function caused by chemotherapy / radiotherapy, immunosuppressants, or treatment of autoimmune diseases; disease-related impaired immune system function (e.g., in patients with HIV / AIDS, hematologic malignancies, advanced kidney disease, cirrhosis, or uncontrolled diabetes); or impaired immune system function due to malnutrition; and naturally impaired immune function in the elderly.

[0042] As used herein, the term "vinorelbine" refers to a semi-synthetic vinca alkaloid with broad-spectrum antitumor activity and low toxicity. It exerts its cytotoxic effect by interfering with the aggregation of microtubules during cell mitosis. Vinorelbine has a strong myelosuppressive effect and can reduce the body's immunity. Vinorelbine causes relatively severe hypoimmunity or immunodeficiency. Those skilled in the art should understand that components that can improve hypoimmunity caused by vinorelbine can also improve hypoimmunity caused by other reasons.

[0043] As used herein, the terms "individual" or "subject" refer to any animal, such as a mammal, preferably a human. In some embodiments, the subject is an immunocompromised subject. In some embodiments, the subject is an immunocompetent subject or a healthy subject. In some embodiments, the subject is a subject who needs to enhance their immunity.

[0044] Nutritional composition

[0045] This invention discovers that when medium- and long-chain triglycerides (MLCT) and milk fat globule membranes (MFGM) are used in combination at a defined mass ratio, there is a synergistic effect between the two, which can be used to prepare foods or medicines that enhance immunity.

[0046] The first aspect of this invention provides a nutritional composition comprising MLCT and MFGM. The mass ratio of MLCT to MFGM is from 0.3:1 to 120:1, for example 0.3:1, 0.6:1, 0.9:1, 1.2:1, 1.5:1, 1.8:1, 2.1:1, 2.4:1, 2.7:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1, 12:1, 14:1, 16:1, 18:1, 2... The mass ratio of MLCT to MFGM is 0:1, 22:1, 24:1, 26:1, 28:1, 30:1, 35:1, 40:1, 45:1, 50:1, 55:1, 60:1, 65:1, 70:1, 75:1, 80:1, 85:1, 90:1, 95:1, 100:1, 105:1, 110:1, 115:1, or 120:1, or any range therebetween. Preferably, the mass ratio of MLCT to MFGM is from 0.3:1 to 28:1. Preferably, the mass ratio of MLCT to MFGM is from 0.3:1 to 24:1. Preferably, the mass ratio of MLCT to MFGM is from 20:1 to 28:1. Most preferably, the mass ratio of MLCT to MFGM is 0.3:1, 6:1, 24:1, or 120:1.

[0047] product

[0048] A second aspect of this invention relates to products comprising the nutritional compositions described herein. The products may be, for example, food or pharmaceuticals. Foods may be, for example, functional foods, health foods, or health supplements. Those skilled in the art will readily understand that, in addition to the nutritional compositions of this invention, the food may also include one or more other product components, such as one or more selected from: raw milk, demineralized whey powder, whey protein concentrate, lactose, blended vegetable oils, fructooligosaccharides, galactooligosaccharides, nucleotides, choline, vitamins, minerals, DHA, and taurine. When used as a pharmaceutical product in the nutritional compositions described herein, the product may also contain pharmaceutically acceptable carriers, diluents, or excipients. The product may also contain various food- or pharmaceutically acceptable excipients (e.g., flavorings or colorings). The product may be in any suitable form, such as liquid, solid, powder, gel, etc., as long as it is suitable for use by the subject. When the product is a pharmaceutical product, it may be any dosage form, such as a solid dosage form (powder, tablet, etc.) or a liquid dosage form.

[0049] In some embodiments, the nutritional composition or products thereof are intended for oral human use.

[0050] In some embodiments, the dosage of MLCT can be calculated based on the ratio of MLCT to MFGM in the nutritional composition described herein.

[0051] In some embodiments, the dosage of MFGM can be calculated based on the ratio of MLCT to MFGM as described herein for the nutritional composition.

[0052] Methods and uses

[0053] A third aspect of the invention relates to the use of the nutritional compositions described herein in the preparation of products for enhancing immunity.

[0054] In this article, boosting immunity can be for non-therapeutic or therapeutic purposes.

[0055] When boosting immunity is not for therapeutic purposes, the nutritional composition can be used to prepare foods such as regular foods, functional foods, or health foods. When boosting immunity is for therapeutic purposes, the nutritional composition can be formulated into a pharmaceutical product.

[0056] In one implementation, enhancing immunity includes, for example, enhancing systemic immunity in healthy subjects, or improving or restoring reduced T cell numbers and / or reduced macrophage numbers and / or reduced neutrophil numbers in subjects with low immunity.

[0057] A fourth aspect of the invention relates to a method for enhancing the immunity of a subject, comprising administering to the subject the nutritional composition or product described herein. In one embodiment, the nutritional composition or product described herein is administered orally to the subject.

[0058] In one embodiment of the foregoing aspects, the product is a pharmaceutical product or a food product. Preferably, the food product is a health supplement. Preferably, the food product is selected from dairy products, confectionery, beverages, bread, and biscuits. Preferably, the food product is milk powder or fermented food. Preferably, the milk powder is infant formula. In one embodiment of the foregoing aspects, the dosage form of the pharmaceutical product is selected from powders, tablets, and liquids. In one embodiment, enhancing immunity includes improving or restoring the reduced number of macrophages and / or the reduced number of T cells and / or the reduced number of neutrophils in subjects with low immunity.

[0059] The nutritional compositions or products described herein can be applied to healthy individuals or subjects, or to subjects with low or weakened immunity. Preferably, the nutritional compositions or products described herein are applied to subjects with low or weakened immunity (particularly human subjects). In one embodiment, the subject with low immunity is a subject with primary immunodeficiency or secondary immunodeficiency.

[0060] A fifth aspect of the invention relates to the use of the nutritional composition described herein in the preparation of a medicament for treating or preventing immunodeficiency. A sixth aspect of the invention relates to a method for treating or preventing immunodeficiency in a subject, comprising administering the nutritional composition described herein to the subject.

[0061] In one embodiment, enhancing immunity includes, for example, improving or restoring a reduced number of T cells and / or a reduced number of macrophages and / or a reduced number of neutrophils in immunocompromised subjects. In one embodiment, the immunocompromise is caused by primary or secondary immunodeficiency. In one embodiment, the immunocompromise is post-chemotherapy immunocompromise. In one embodiment, the chemotherapy is vinorelbine treatment. In one embodiment, the nutritional composition may be administered before, after, or concurrently with chemotherapy.

[0062] The invention will be more readily understood by referring to the following examples, which are only used to illustrate certain aspects and embodiments of the invention and are not intended to limit the invention.

[0063] Example

[0064] Unless otherwise specified, all raw materials used in this invention are commercially available or commonly used in the field. Unless otherwise specified, the methods in the following embodiments are conventional methods in the field.

[0065] Unless otherwise stated, all reagents used in this embodiment are commercially available or conventional materials. The medium- and long-chain fatty acid triglycerides in all the following embodiments are derived from medium- and long-chain fatty acid edible oils with a purity of 69±10%, produced by Qingdao Haizhiyuan Life Science Technology Co., Ltd., batch number Y1505-22120101; MFGM, purchased from Arla, product name Lacprodan® MFGM-10, batch number P510216, contains 8±2% phospholipids, 71.5±5% protein by weight, and 25±10g sphingomyelin / 100g phospholipids.

[0066] Example 1: Determination of Maximum Tolerated Concentration (MTC) for a Single Sample

[0067] Three-day-old (3 dpf) transgenic T-cell red fluorescent zebrafish were randomly selected and placed in 6-well plates, with 30 zebrafish treated in each well (experimental group). Samples were administered in water (concentrations shown in Table 1). 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 experimental groups received intravenous injection of vinorelbine tartrate injection to establish a zebrafish immunodeficiency model. After treatment at 28℃ for 48 h, the MTC of the samples in the model zebrafish was measured.

[0068] Table 1. Results of the experiment to determine the maximum detectable concentration of a single sample to enhance immunity (n = 30)

[0069]

[0070] As shown in Table 1, the MTC of medium- and long-chain fatty acid triglycerides was 2000 μg / mL; the MTC of milk fat globule membrane (MFGM) was 175 μg / mL. Subsequent dosing experiments were designed based on the above MTC values.

[0071] Example 2: Evaluation Experiment of Enhanced Immune Function (Effect of Increasing T Cell Fluorescence Intensity)

[0072] Three-day-old (3 dpf) transgenic T-cell fluorescent zebrafish were randomly selected and placed in 6-well plates, with 30 zebrafish treated in each well (experimental group). Water-soluble samples (concentrations shown in Table 2) were administered, along with a positive control of 15.0 μg / mL of Bailin capsules. A normal control and a model control group were also included, with a volume of 3 mL per well. Except for the normal control group, all other experimental groups received intravenous injection of vinorelbine tartrate injection to establish a zebrafish immunodeficiency model. After treatment at 28℃ for 48 h, 10 zebrafish from each experimental group were randomly selected and photographed under a fluorescence microscope. Data were collected using NIS-Elements D 3.20 advanced image processing software, and the fluorescence intensity of zebrafish T cells was analyzed. Statistical analysis of this index was used to evaluate the immune-enhancing efficacy (increased T-cell fluorescence intensity efficacy). Statistical results are expressed as mean ± SE. Statistical analysis was performed using SPSS software; P < 0.05 indicated statistical significance. The synergistic increase refers to the sum of the recovery amount of the formulation group and the recovery amount of the corresponding concentration of individual samples. The synergistic coefficient is calculated as follows: recovery amount of the formulation group / sum of the recovery amounts of the corresponding concentration of individual samples, where the recovery amount of the formulation group is the fluorescence intensity of the formulation treatment group minus the fluorescence intensity of the model control group, and the recovery amount of an individual sample is the fluorescence intensity of the individual sample treatment group minus the fluorescence intensity of the model control group. The contribution rate of the synergistic coefficient per unit dose is calculated as follows: contribution rate of the synergistic coefficient per unit dose = synergistic coefficient / total dose.

[0073] Table 2. Results of the experiment evaluating the efficacy of the samples in improving immunity (T cell fluorescence intensity) (n = 30)

[0074]

[0075] Note: Compared with the model control group, *P<0.05, **P<0.01, ***P<0.001.

[0076] From Table 2, Figure 1The results showed that intravenous injection of vinorelbine tartrate injection into transgenic T-cell red fluorescent zebrafish 3 days post-fertilization (3 dpf) significantly reduced T-cell fluorescence intensity, indicating the successful establishment of a zebrafish immunodeficiency model. Compared with the model control group, the positive control drug (Bailing capsules), monomeric MLCT (1500 µg / mL), and monomeric MFGM (50.0 µg / mL, 200 µg / mL) all significantly improved immunity, specifically by a significant increase in T-cell fluorescence intensity compared to the model control (P < 0.05). Furthermore, compared with the model control, the combined use of MLCT and MFGM (1-4) significantly improved immunity, specifically by a significant enhancement of T-cell fluorescence intensity (P < 0.05), and a synergistic effect was observed between the two. For example, in Table 2, compared to the model control group, the T cell fluorescence intensity (pixels) of Formula 1, Comparative Example 1, and Comparative Example 6 increased by 40,730 pixels, 1,271 pixels, and 33,960 pixels, respectively. The increase in T cell fluorescence intensity in Formula 1 (40,730 pixels) was greater than the sum of the increases in Comparative Example 1 and Comparative Example 4 (35,231 pixels). Similarly, Formulas 2-4 also showed a synergistic effect, meaning that MLCT and MFGM had a synergistic effect in improving immune efficacy when the ratio was 0.3-120.

[0077] On the other hand, regarding the synergistic coefficient, the synergistic coefficient of Formula 1 is the ratio of the increase in T cell fluorescence intensity of Formula 1 to the sum of the increases in T cell fluorescence intensity of Comparative Examples 1 and 6, i.e., synergistic coefficient 1.156 > 1, indicating a synergistic effect between MLCT and MFGM, which can synergistically increase the fluorescence intensity of T cells in individuals with low immunity. Similarly, for Formulas 2-4, a synergistic effect between MLCT and MFGM can also be concluded, which can synergistically increase the fluorescence intensity of T cells in individuals with low immunity. That is, Formulas 1-4 with an MLCT:MFGM mass ratio of 0.3-120:1 have a synergistic effect in improving the fluorescence intensity of T cells in individuals with low immunity (synergistic coefficients are all greater than 1).

[0078] Specifically, the synergistic coefficients of formulations 1-4 per unit dose are ranked as follows: formulation 2 > formulation 1 = formulation 3 > formulation 4. Therefore, when the mass ratio of MLCT to MFGM is 0.3:1 to 120:1, preferably 0.3:1 to 24:1, a satisfactory synergistic coefficient per unit dose is observed in improving the fluorescence intensity of T cells in individuals with low immunity.

[0079] Example 3: Evaluation Experiment of Enhanced Immune Function (Effect of Increasing Macrophage Fluorescence Intensity)

[0080] 30 zebrafish with 3 dpf transgenic macrophages and green fluorescent fluorescence were randomly selected and placed in 6-well plates, with each well (experimental group) containing 30 zebrafish. Water-soluble samples (concentrations shown in Table 3) were administered, along with a positive control of 15.0 μg / mL of Bailin capsules. 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 experimental groups received intravenous injection of vinorelbine tartrate injection to establish a zebrafish immunodeficiency model. After treatment at 28℃ for 48 h, 10 zebrafish from each experimental group were randomly selected and photographed under a fluorescence microscope. Data were collected using NIS-Elements D 3.20 advanced image processing software, and the fluorescence intensity of zebrafish macrophages was analyzed. The statistical analysis results of this index were used to evaluate the immune-enhancing efficacy (efficacy of increasing macrophage fluorescence intensity). Statistical results are expressed as mean ± SE. Statistical analysis was performed using SPSS software; p < 0.05 indicated statistical significance. The synergistic increase refers to the sum of the recovery amount of the formulation group and the recovery amount of the corresponding concentration of individual samples. The synergistic coefficient is calculated as follows: recovery amount of the formulation group / sum of the recovery amounts of the corresponding concentration of individual samples, where the recovery amount of the formulation group is the fluorescence intensity of the formulation treatment group minus the fluorescence intensity of the model control group, and the recovery amount of an individual sample is the fluorescence intensity of the individual sample treatment group minus the fluorescence intensity of the model control group. The contribution rate of the synergistic coefficient per unit dose is calculated as follows: contribution rate of the synergistic coefficient per unit dose = synergistic coefficient / total dose.

[0081] Table 3. Results of the experiment evaluating the efficacy of the samples in improving immunity (macrophage fluorescence intensity) (n = 30)

[0082]

[0083] Note: Compared with the model control group, *P<0.05, **P<0.01, ***P<0.001.

[0084] From Table 3, Figure 2The results showed that, compared with the model control group, the positive control drug (Bailing capsules), monomeric MLCT (1500 µg / mL), and monomeric MFGM (12.5 µg / mL, 50 µg / mL, 200 µg / mL) all significantly improved immunity, specifically by a significant increase in macrophage fluorescence intensity compared with the model control (P < 0.05). Furthermore, compared with the model control, the combined use of MLCT and MFGM (1-4) significantly improved immunity, specifically by a significant increase in macrophage fluorescence intensity (P < 0.05), and there was a synergistic effect between the two. For example, compared with the model control group, the macrophage fluorescence intensity (pixels) of formulations 1, 1, and 6 in Table 3 increased by 21159 pixels, 1130 pixels, and 19074 pixels, respectively. The increase in macrophage fluorescence intensity in formulation 1 (21159 pixels) was greater than the sum of the increases in 1 and 4 (20204 pixels). Similarly, formulations 2-4 also concluded that they have a synergistic effect, that is, MLCT and MFGM have a synergistic effect in improving immune efficacy when the ratio is 0.3-120.

[0085] On the other hand, regarding the synergy coefficient, the synergy coefficient of Formula 1 is the ratio of the increase in macrophage fluorescence intensity of Formula 1 to the sum of the increases in macrophage fluorescence intensity of Comparative Examples 1 and 6, i.e., synergy coefficient 1.047 > 1, indicating a synergistic effect between MLCT and MFGM, which can synergistically increase the fluorescence intensity of macrophages in individuals with low immunity. Similarly, for Formulas 2-4, the conclusion that there is a synergistic effect between MLCT and MFGM, which can synergistically increase the fluorescence intensity of macrophages in individuals with low immunity can also be drawn. That is, Formulas 1-4 with an MLCT:MFGM mass ratio of 0.3-120:1 have a synergistic effect in improving the fluorescence intensity of macrophages in individuals with low immunity (synergy coefficients are all greater than 1).

[0086] Specifically, the synergistic coefficients of formulations 1-4 per unit dose are ranked as follows: formulation 1 > formulation 2 = formulation 3 > formulation 4. Therefore, when the mass ratio of MLCT to MFGM is 0.3:1 to 120:1, preferably 0.3:1 to 24:1, a satisfactory synergistic coefficient per unit dose is observed in improving the fluorescence intensity of macrophages in individuals with low immunity.

[0087] Example 4: Evaluation Experiment of Enhanced Immune Function (Effect of Increasing Neutrophil Fluorescence Intensity)

[0088] 3-day-first-flush (dpf) transgenic green fluorescent zebrafish with neutrophils were randomly selected and placed in 6-well plates, with 30 zebrafish treated in each well (experimental group). Water-soluble samples (concentrations shown in Table 4) were administered, along with a positive control of 15.0 μg / mL of Bailin capsules. 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 experimental groups received intravenous injection of vinorelbine tartrate injection to establish a zebrafish immunodeficiency model. After treatment at 28℃ for 48 h, 10 zebrafish from each experimental group were randomly selected and photographed under a fluorescence microscope. Data were collected using NIS-Elements D 3.20 advanced image processing software, and the number of neutrophils in the zebrafish was analyzed. The statistical analysis results of this indicator were used to evaluate the immune-enhancing efficacy (efficacy in increasing neutrophil count). Statistical results are expressed as mean ± SE. Statistical analysis was performed using SPSS software; p < 0.05 indicated statistical significance. The contribution rate of the synergistic coefficient per unit dose was calculated as follows: Contribution rate of synergistic coefficient per unit dose = Synergistic coefficient / Total dose.

[0089] Table 4. Results of the experiment evaluating the efficacy of the samples in improving immunity (neutrophil count) (n = 30)

[0090]

[0091] Note: Compared with the model control group, *P<0.05, **P<0.01, ***P<0.001.

[0092] From Table 4, Figure 3 The results showed that, compared with the model control group, the positive control drug (Bailing capsules), monomeric MLCT (300 µg / mL, 1500 µg / mL), and monomeric MFGM (50 µg / mL, 200 µg / mL) all significantly improved immunity, specifically by a significant increase in neutrophil fluorescence intensity compared with the model control (P < 0.05). Furthermore, compared with the model control, the combined use of MLCT and MFGM (1-4) significantly improved immunity, specifically by a significant enhancement in neutrophil fluorescence intensity (P < 0.05), and there was a synergistic effect between the two. For example, in Table 4, compared with the model control group, formulations 1, 1, and 6 showed increases in neutrophil fluorescence intensity (pixels) of 10.3 pixels, 1.9 pixels, and 7.6 pixels, respectively. The increase in neutrophil fluorescence intensity in formulation 1 (10.3 pixels) was greater than the sum of the increases in 1 and 4 (9.5 pixels). Similarly, formulations 2-4 also concluded that they have a synergistic effect, that is, MLCT and MFGM have a synergistic effect in improving immune efficacy when the ratio is 0.3-120.

[0093] On the other hand, regarding the synergistic coefficient, the synergistic coefficient of Formula 1 is the ratio of the increase in neutrophil fluorescence intensity of Formula 1 to the sum of the increases in neutrophil fluorescence intensity of Comparative Examples 1 and 6, i.e., synergistic coefficient 1.084 > 1, indicating a synergistic effect between MLCT and MFGM, which can synergistically increase the fluorescence intensity of neutrophils in individuals with low immunity. Similarly, for Formulas 2-4, the conclusion that there is a synergistic effect between MLCT and MFGM, which can synergistically increase the fluorescence intensity of neutrophils in individuals with low immunity can also be drawn. That is, Formulas 1-4 with an MLCT:MFGM mass ratio of 0.3-120:1 have a synergistic effect in improving the fluorescence intensity of neutrophils in individuals with low immunity (synergistic coefficients are all greater than 1).

[0094] Specifically, the synergistic coefficients of formulations 1-4 per unit dose are ranked as follows: formulation 2 > formulation 1 > formulation 3 > formulation 4. Therefore, when the mass ratio of MLCT to MFGM is 0.3:1 to 120:1, preferably 0.3:1 to 24:1, a satisfactory synergistic coefficient per unit dose is observed in improving neutrophil count in individuals with low immunity.

[0095] The above embodiments are only used to illustrate the technical solutions of the present invention, and are not intended to limit it. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. Use of a nutritional composition for non-therapeutic purposes for the enhancement of immunity, characterized in that, The nutritional composition comprises medium- and long-chain fatty acid triglycerides (MLCT) and milk fat globule membranes (MFGM) in a mass ratio of 0.3:1 to 120:

1.

2. Use according to claim 1, characterized in that, The mass ratio of MLCT to MFGM ranges from 0.3:1 to 28:

1.

3. Use according to claim 2, characterized in that, The mass ratio of MLCT to MFGM is 20:1 to 28:

1.

4. Use according to any one of claims 1 to 3, characterized in that, The enhancement of immunity includes enhancing systemic immunity, or restoring the reduced number of T cells and / or the reduced number of macrophages and / or the reduced number of neutrophils in subjects with low immunity.

5. Use according to claim 4, characterized in that, The subjects with low immunity are either those with primary immunodeficiency or those with secondary immunodeficiency.

6. Use of a nutritional composition for the manufacture of a product for enhancing immunity, characterized in that, The nutritional composition comprises medium- and long-chain fatty acid triglycerides (MLCT) and milk fat globule membranes (MFGM) in a mass ratio of 0.3:1 to 120:

1.

7. The use according to claim 6, characterized in that, The mass ratio of MLCT to MFGM ranges from 0.3:1 to 28:

1.

8. The use according to claim 7, characterized in that, The mass ratio of MLCT to MFGM is 20:1 to 28:

1.

9. The use according to any one of claims 6-8, characterized in that, The product in question is either a pharmaceutical or a food product.

10. The use according to claim 9, characterized in that, The food products mentioned include ordinary food, health food, special medical food, or infant formula.

11. The use according to claim 9, characterized in that, The food products include fermented foods.

12. The use according to claim 9, characterized in that, The food products mentioned include dairy products.

13. The use according to claim 9, characterized in that, The food items include beverages, bread, biscuits, and candy.

14. The use according to claim 9, characterized in that, The food products mentioned are children's formula milk powder, teenager's milk powder, formula milk powder for pregnant women, or milk powder for middle-aged and elderly people.

15. The use according to claim 6, characterized in that, The enhanced immunity includes enhancing systemic immunity, restoring reduced T cell counts and / or reduced macrophage counts and / or reduced neutrophil counts in subjects with low immunity.

16. The use according to claim 15, characterized in that, The low immunity mentioned refers to low immunity caused by primary or secondary immunodeficiency.

17. The use of a nutritional composition in the preparation of a medicament for treating or preventing immunodeficiency, characterized in that, The nutritional composition comprises medium- and long-chain fatty acid triglycerides (MLCT) and milk fat globule membranes (MFGM) in a mass ratio of 0.3:1 to 120:

1.

18. The use according to claim 17, characterized in that, The mass ratio of MLCT to MFGM ranges from 0.3:1 to 28:

1.

19. The use according to claim 17, characterized in that, The mass ratio of MLCT to MFGM is 20:1 to 28:

1.

20. The use according to any one of claims 17-19, characterized in that, The aforementioned low immunity refers to low immunity caused by primary or secondary immunodeficiency.

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