Use of a composition for improving eczema

Abstract

This invention provides the use of compositions for improving eczema. The compositions of this invention comprise medium- and long-chain fatty acid triglycerides (MLCT) and milk fat globule membranes (MFGM) in a mass ratio of 0.4:1 to 40:1. The eczema includes atopic eczema. The compositions have a synergistic effect in improving eczema, such as atopic eczema.

Description

Technical Field

[0001] This application relates to the use of the composition, and in particular to the use of the composition in the preparation of products for eczema (e.g., allergic eczema). Background Technology

[0002] Eczema is an inflammation of the epidermis and superficial dermis caused by a variety of internal and external factors. Clinically, the skin lesions in the acute phase are mainly papules and vesicles with a tendency to ooze, while the chronic phase is mainly lichenification and is prone to recurrence. The incidence of eczema is on the rise globally, affecting 2.0% of adults and 4.0% of children. The pathogenesis of eczema is related to the interaction between genetic and environmental factors, skin barrier dysfunction, microbial imbalance, immune dysregulation and skin inflammation (Zhang Aili, Xu Na, Wang Juan, et al. Peripheral serum levels of 25-hydroxyvitamin D, IL-4, IL-10 and IL-17 in adult eczema and their clinical significance [J]. Guizhou Medical Journal, 2026, 50(03):467-473).

[0003] Medium- and long-chain triglycerides (MLCTs) have one or two medium-chain fatty acids attached to their glycerol backbone, while the others are long-chain fatty acids. Administration of MLCTs can cause gastrointestinal discomfort, and long-term use of MCTs carries the risk of ketoacidosis or ketoacidosis, while long-chain triglycerides (LCTs) are poorly absorbed. Compared to LCTs or MCTs, natural or synthetic MLCTs have unique composition, structure, and metabolic characteristics, and are therefore closely related to beneficial physiological functions. Early studies have shown that 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 (Yuan Tinglan, Wei Wei, Ye Xingwang, et al. Research progress on medium- and long-chain triglycerides in breast milk [J]. Journal of Food and Biotechnology, 2022, 41(6):10). Furthermore, even with the same overall fatty acid composition, different triglyceride structures result in significant differences in their biological functions. For example, mouse studies have shown that, compared to feeding mice with a formulated lipid diet containing a physically mixed vegetable oil of LCT / MCT with the same fatty acid composition, feeding them a formulated diet containing MLCT structured esters has the functions of regulating thermogenesis, inhibiting visceral fat accumulation, altering gut microbiota, and regulating lipid metabolism (Yuan T, Cheng X, Shen L, Liu Z, Ye X, Yan Z, Wei W, Wang X. Novel Human Milk Fat Substitutes Based on Medium- and Long-Chain Triacylglycerol Regulate Thermogenesis, Lipid Metabolism, and Gut Microbiota Diversity in C57BL / 6JMice. J Agric Food Chem. 2024 Mar 27;72(12):6213-6225.). However, there are no reports on its association with allergies and eczema.

[0004] The milk fat globule membrane is a three-layered membrane structure surrounding milk fat droplets. Natural milk fat globule membranes gradually form during the release of fat from mammary endothelial cells. The triglyceride droplets within are initially encased by a single-layer phospholipid membrane from the endoplasmic reticulum and migrate towards the apical membrane of the cell. They are then encased by a double-layered phospholipid cytoplasmic membrane at the apex of the mammary cell, forming a unique three-layered membrane structure: a single-layered phospholipid membrane on the inner side and a double-layered biological membrane on the outer side. The milk fat globule membrane is mainly composed of lipids such as phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, phosphatidylserine, sphingomyelin, glycolipids, gangliosides, and cholesterol, as well as membrane-specific proteins and mucopolysaccharides. It can promote infant cognitive development and enhance infant immunity (Chinese Institute of Food Science and Technology; Scientific Consensus on Milk Fat Globule Membrane and its Ingredients [J]; Chinese Journal of Food Science; 2022, Issue 04). Currently, there is no clear research indicating a relationship between milk fat globule membrane and eczema improvement.

[0005] The purpose of this invention is to explore the efficacy of a combination of medium- and long-chain triglycerides (MLCT) and milk fat globule membranes (MFGM) in improving eczema. Summary of the Invention

[0006] This application is made in view of the aforementioned problems existing in the prior art.

[0007] In a first aspect, this application relates to a composition comprising a medium- and long-chain triacylcerol (MLCT) and a milk fat globule membrane (MFGM), wherein the mass ratio of the MLCT to the MFGM is from 0.4:1 to 40:1.

[0008] In some embodiments, the mass ratio of the MLCT to the MFGM is from 1:1 to 40:1.

[0009] In some implementations, the mass ratio of the MLCT to the MFGM is 1:1 to 5:1.

[0010] In a second aspect, this application also relates to a product comprising the composition described in the first aspect of this application.

[0011] In a third aspect, this application also relates to the use of the composition according to the first aspect of this application in the preparation of a product for improving eczema.

[0012] In a fourth aspect, this application also relates to the use of the composition according to the first aspect of this application in the preparation of a medicament for improving eczema.

[0013] In some embodiments, the eczema is allergic eczema.

[0014] In some implementations, improving eczema includes preventing eczema or relieving one or more symptoms of eczema.

[0015] In some embodiments, the improvement of eczema includes one or more of relieving itching and reducing trypsin levels.

[0016] In some embodiments, the product is used in such a quantity that the intake of medium- and long-chain fatty acid triglycerides is 2.25 g to 30.0 g per day.

[0017] The beneficial effects of this application include: when MLCT and MFGM are used in combination at a specific mass ratio, they exhibit a synergistic effect in improving eczema (e.g., allergic eczema), particularly in relieving itching and reducing trypsin levels. The combined effect is superior to the effect of using the same amount of MLCT alone or the same amount of MFGM alone, and also superior to the sum of the effects of using the same amount of MLCT alone and the same amount of MFGM alone. For example, when MLCT and MFGM are used at a mass ratio of 0.4:1 to 40:1, the composition can synergistically relieve itching and / or reduce trypsin levels, thereby improving eczema. Preferably, when MLCT and MFGM are used at a mass ratio of 1:1 to 40:1, or at a mass ratio of 1:1 to 5:1, the composition can synergistically relieve itching and / or reduce trypsin levels, thereby improving eczema. Attached Figure Description

[0018] To more clearly illustrate the technical solutions of this application, the accompanying drawings required for describing the embodiments will be briefly described below. It should be understood that these drawings are only for the purpose of facilitating a better understanding of this application by those skilled in the art, and are not intended to limit the scope of this application.

[0019] Figure 1 Typical total movement distance of zebrafish after sample treatment. Note: Black line represents slow movement distance, green line represents medium movement distance, and red line represents fast movement distance. Detailed Implementation

[0020] 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.

[0021] Terminology Definition

[0022] 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.

[0023] In this application, unless otherwise specified, the temperature is room temperature (e.g., 25°C), the atmosphere is air, and the pressure is normal pressure (e.g., 1 atmosphere).

[0024] In this application, the term "medium-chain fatty acid" refers to fatty acids with 6 to 12 carbon atoms in their carbon chain, such as hexanoic acid, heptanoic acid, octanoic acid, nonanoic acid, decanoic acid, undecanoic acid, and dodecanoic acid. The term "long-chain fatty acid" refers to fatty acids with 14 or more carbon atoms in their carbon chain, generally 14 to 30 carbon atoms, such as myristic acid, palmitic acid, oleic acid, linoleic acid, stearic acid, linolenic acid, arachidonic acid, eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid. The terms "medium-chain fatty acid triglyceride" (MCT) and "long-chain fatty acid triglyceride" (LCT) refer to the esterification products of medium-chain fatty acids and long-chain fatty acids with glycerol, respectively. The term "medium- and long-chain fatty acid triglycerides" refers to triglycerides that contain both medium-chain fatty acid residues and long-chain fatty acid residues in their molecular structure.

[0025] 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 improve eczema.

[0026] This application relates to compositions comprising MLCT and MFGM, products comprising the above compositions, the use of the above compositions in the preparation of products for improving eczema (e.g., allergic eczema), and the use of the above compositions or products for improving eczema (e.g., allergic eczema). The application will be described in detail below.

[0027] Composition

[0028] A first aspect of this application provides a composition comprising medium- and long-chain fatty acid triglycerides (MLCT) and milk fat globule membranes (MFGM), wherein the mass ratio of MLCT to MFGM is from 0.4:1 to 40:1.

[0029] As used in this article, "medium- and long-chain triglycerides" (MLCT) refers to triglycerides with one or two medium-chain fatty acids linked to the glycerol backbone, and the remainder being long-chain fatty acids. High doses of medium-chain triglycerides (MCT) can easily induce gastrointestinal discomfort, and long-term use carries the risk of ketoacidosis or ketoacidosis; while long-chain triglycerides (LCT) have lower absorption efficiency. Compared with LCT or MCT, natural or synthetic MLCT has unique composition, structure, and metabolic characteristics, and is therefore closely related to a variety of beneficial physiological functions. Early studies have shown that the fatty acid composition of MLCT is closer to that of breast milk, which helps in the digestion and absorption of fat, improves the utilization efficiency of fat-soluble nutrients, inhibits the accumulation of body fat, and can provide energy quickly and stably (Yuan Tinglan, Wei Wei, Ye Xingwang, et al. Research progress on medium- and long-chain triglycerides in breast milk [J]. Journal of Food and Biotechnology, 2022, 41(6):10.). In addition, under the same total fatty acid composition, the differences in the molecular structure of triglycerides can significantly affect their biological functions. For example, mouse experiments have shown that, compared with mice fed a diet containing a physical mixture of LCT / MCT vegetable oils with the same fatty acid composition, mice fed a diet containing MLCT structured esters exhibited effects such as thermoregulation, inhibition of visceral fat accumulation, alteration of gut microbiota, and regulation of lipid metabolism (Yuan T, Cheng X, Shen L, Liu Z, Ye X, Yan Z, Wei W, Wang X. Novel Human Milk Fat Substitutes Based on Medium- and Long-Chain Triacylglycerol Regulate Thermogenesis, Lipid Metabolism, and Gut Microbiota Diversity in C57BL / 6J Mice. J Agric Food Chem. 2024 Mar 27;72(12):6213-6225.). However, there are currently no reports on the correlation between MLCT and allergies or eczema.

[0030] As is known in the art, medium- and long-chain fatty acid triglycerides are produced by using edible vegetable oils and MCTs as raw materials, through transesterification by lipases, followed by processes such as distillation, decolorization, and deodorization.

[0031] This application does not have any particular requirements regarding the medium- and long-chain triglycerides used; medium- and long-chain triglycerides commonly used in the art can be used. Medium- and long-chain triglycerides can be used in pure form or in a non-pure form rich in medium- and long-chain triglycerides. For example, the medium- and long-chain triglycerides used in the compositions of this application can be medium- and long-chain triglycerides with a single composition (i.e., each molecular chain has the same long-chain fatty acid residues and the same medium-chain fatty acid residues), or a mixture of multiple medium- and long-chain triglycerides with two or more different compositions (i.e., each molecular chain has different long-chain fatty acid residues and / or different medium-chain fatty acid residues).

[0032] In some embodiments, the medium- and long-chain fatty acid triglycerides used in this application may comprise C6-C12 (e.g., the range defined by C6, C7, C8, C9, C10, C11, C12, or any two thereof) fatty acid residues and C14-C30 (e.g., the range defined by C14, C15, C16, C17, C18, C19, C20, C21, C22, C23, C24, C25, C26, C27, C28, C29, C30, or any two thereof) fatty acid residues. In some examples, the C6-C12 fatty acid residues may be derived from one or more of the following: hexanoic acid, heptanoic acid, octanoic acid, nonanoic acid, decanoic acid, undecanoic acid, and lauric acid, etc. C14–C30 fatty acid residues may be derived from one or more of the following: myristic acid, palmitic acid, heptadecanic acid, oleic acid, linoleic acid, stearic acid, nonadecanic acid, eicosapentaenoic acid, docosapentaenoic acid, docosahexaenoic acid, tricarboxylic acid, docosapentaenoic acid, docosahexaenoic acid, arachidonic acid, etc. In some examples, C6–C12 fatty acid residues may be derived from one or more of the following: hexanoic acid, octanoic acid, capric acid, and lauric acid. In some examples, C14–C30 fatty acid residues may be derived from one or more of the following: myristic acid, palmitic acid, oleic acid, linoleic acid, stearic acid, linolenic acid, arachidonic acid, eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid.

[0033] In some embodiments, the weight ratio of C6-C12 fatty acid residues to C14-C30 fatty acid residues in the medium- and long-chain fatty acid triglycerides used in this application may be from 0.124 to 2.000. For example, in the medium- and long-chain fatty acid triglycerides used in this application, the unit weight ratio of C6-C12 fatty acid residues to C14-C30 fatty acid residues may be 0.124, 0.125, 0.130, 0.140, 0.150, 0.160, 0.170, 0.180, 0.190, 0.200, 0.300, 0.400, 0.500, 0.600, 0.700, 0.800, 0.900, 1.000, 1.100, 1.200, 1.300, 1.400, 1.500, 1.600, 1.700, 1.800, 1.900, 2.000, or any two of these ranges.

[0034] As used herein, the term "milk fat globule membrane" or "MFGM" (Milk Fat Globule Membrane) 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 of 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. CN119999771A mentions that the simulated breast milk phospholipids it provides have a high milk fat globule membrane and phospholipid formation rate, and high quality and safety; it can be used in the preparation of infant formula to reduce the occurrence of inflammation and allergic reactions in infants and improve fat utilization. However, there is currently no clear research showing a relationship between milk fat globule membrane and eczema improvement.

[0035] The present invention does not particularly limit the method for extracting MFGM from the aforementioned animal milk or its products. 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. Furthermore, 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 separation, concentration, and drying processes. Milk fat globule membrane milk protein powder refers to a powdered product containing milk fat globule membranes, made from raw milk or cream through separation, concentration, and drying processes.

[0036] Commercial sources of the 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.

[0037] In some embodiments, the mass ratio of MLCT to MFGM in the compositions of this application is from 0.4:1 to 40:1. When MLCT and MFGM are used in combination at mass ratios within the above range, the compositions of this application exhibit a significant synergistic effect in improving eczema (e.g., atopic eczema), particularly in relieving itching and / or reducing trypsin levels. As examples, the mass ratio of MLCT to MFGM can be 0.4:1, 0.5:1, 0.6:1, 0.7:1, 0.8:1, 0.9:1, 1:1, 1.2:1, 1.4:1, 1.5:1, 1.6:1, 1.8:1, 2.0:1, 2.2:1, 2.4:1, 2.6:1, 2.8:1, 3.0:1, 3.2:1, 3.4:1, 3.6:1, 3.8:1, 4.0:1, 4.2:1, 4.4:1, 4.5:1, 4.8:1 5.0:1, 5.5:1, 6.0:1, 6.5:1, 7.0:1, 7.5:1, 8.0:1, 8.5:1, 9.0:1, 9.5:1, 10:1, 11:1, 12:1, 13:1, 13.5:1, 14:1, 15:1, 16:1, 17:1, 18:1, 19:1, 20:1, 22:1, 24:1, 28:1, 32:1, 34:1, 36:1, 38:1 or 40:1, or within the range defined by any two of the above. More specifically, the mass ratio of MLCT to MFGM can be 0.493:1, 1.48:1, 4.44:1, 4.45:1, 13.33:1, 13.34:1 or 40:1, or within any two of the above ranges.

[0038] Preferably, the mass ratio of MLCT to MFGM is from 1:1 to 40:1. Alternatively, preferably, the mass ratio of MLCT to MFGM is from 1:1 to 5:1. When MLCT and MFGM are used in combination at mass ratios within the above ranges, the synergistic effect of the composition of this application in improving eczema (e.g., allergic eczema), particularly in relieving itching and / or reducing trypsin levels, is more pronounced.

[0039] In some embodiments, the composition of this application may consist of MLCT and MFGM, for example, MLCT and MFGM in any mass ratio or mass ratio range as described above.

[0040] product

[0041] A second aspect of this application provides a product comprising the composition described in the first aspect of this application.

[0042] All descriptions of the composition above apply here and will not be repeated here.

[0043] In some embodiments, the composition according to the first aspect of this application may be added to a product as a beneficial ingredient.

[0044] The product can be prepared by methods commonly used in the art, which will not be described in detail here.

[0045] In some embodiments, the product includes a pharmaceutical product. The present invention does not place particular requirements on the dosage form of the pharmaceutical product, and commonly used pharmaceutical dosage forms in the art can be used. As examples, the pharmaceutical product of the present invention can be a solid dosage form, such as powder, granules, tablets, capsules, drop pills, pills, etc.; a semi-solid dosage form, such as ointment, cream, eye ointment, gel, etc.; or a liquid dosage form, such as oral liquid dosage forms, such as syrups, mixtures, suspensions, emulsions, etc. Those skilled in the art will readily understand that, depending on the dosage form and application scenario, the pharmaceutical product may also include various pharmaceutically permissible excipients. Furthermore, the pharmaceutical product of the present invention can be prepared by methods commonly used in the art, which will not be elaborated here.

[0046] In some embodiments, the MLCT content can be from 0.1% to 30.0% based on the dry basis weight of the product. As an example, the MLCT content can be 0.1%, 0.15%, 0.2%, 0.25%, 0.3%, 0.35%, 0.4%, 0.45%, 0.5%, 0.55%, 0.6%, 0.65%, 0.7%, 0.75%, 0.8%, 0.85%, 0.9%, 0.95%, 1.0%, 1.5%, 2.0%, 2.5%, 3.0%, 3.5%, 4.0%, 4.5%, 5.0%, 5.5%, 6.0%, 6.5%, 7.0%, 7.5%, 8.0%, 8.5%, 9.0%, 9.5%, 10.0%, 10.5%, 11.0%, 11.5%, 12.0%, 1% based on the weight of the product. 2.5, 13.0, 13.5, 14.0, 14.5, 15.0, 15.5, 16.0, 16.5, 17.0, 17.5, 18.0, 18.5, 19.0, 19.5, 20.0, 20.5, 21.0, 21.5, 22.0, 22.5, 23.0, 23.5, 24.0, 24.5, 25.0, 25.5, 26.0, 26.5, 27.0, 27.5, 28.0, 28.5, 29.0, 29.5, 30.0% (dry basis mass), or within the range defined by any two of the above. Furthermore, in a further embodiment, the MFGM content is calculated proportionally.

[0047] In other embodiments, the MFGM content may be from 0.1% to 30.0% based on the dry basis weight of the product. As an example, the MFGM content may be 0.1%, 0.15%, 0.2%, 0.25%, 0.3%, 0.35%, 0.4%, 0.45%, 0.5%, 0.55%, 0.6%, 0.65%, 0.7%, 0.75%, 0.8%, 0.85%, 0.9%, 0.95%, 1.0%, 1.5%, 2.0%, 2.5%, 3.0%, 3.5%, 4.0%, 4.5%, 5.0%, 5.5%, 6.0%, 6.5%, 7.0%, 7.5%, 8.0%, 8.5%, 9.0%, 9.5%, 10.0%, 10.5%, 11.0%, 11.5%, 12.0% based on the weight of the product. 12.5, 13.0, 13.5, 14.0, 14.5, 15.0, 15.5, 16.0, 16.5, 17.0, 17.5, 18.0, 18.5, 19.0, 19.5, 20.0, 20.5, 21.0, 21.5, 22.0, 22.5, 23.0, 23.5, 24.0, 24.5, 25.0, 25.5, 26.0, 26.5, 27.0, 27.5, 28.0, 28.5, 29.0, 29.5, 30.0% by dry weight, or within the range defined by any two of the above.

[0048] use

[0049] The third aspect of this application provides the use of the composition according to the first aspect of this application in the preparation of a product for improving eczema.

[0050] The fourth aspect of this application provides the use of the composition according to the first aspect of this application in the preparation of a medicament for improving eczema.

[0051] In some implementations, there are no particular limitations on the subjects (recipients) who are improving eczema, and may include, for example, infants, toddlers, children, adolescents, adults, young adults, middle-aged people, and / or the elderly. As used herein, the term “infant” refers to a person aged from birth to 12 months; the term “toddler” refers to a person aged 1 to 3 years; the term “child” refers to a person aged 3 to 7 years; the term “adolescent” refers to a person aged 7 to 17 years; the term “adult” refers to a person aged 18 years or older; the term “young adult” refers to a person aged 18 to 40 years; the term “middle-aged person” refers to a person aged 41 to 65 years; and the term “elderly person” or “senior person” refers to a person aged 65 years or older.

[0052] In some embodiments, the eczema is allergic eczema.

[0053] In some embodiments, the method of improving eczema includes preventing eczema or relieving one or more symptoms of eczema. For example, preventing eczema includes, for instance, preventing the occurrence or development of eczema; and relieving one or more symptoms of eczema includes, for instance, relieving or reducing itching, and / or reducing trypsin levels.

[0054] As described above, when MLCT and MFGM are used in combination at a specific mass ratio (e.g., any mass ratio or range of mass ratios described above), the product used according to the third aspect of this application exhibits a synergistic effect in improving eczema (e.g., allergic eczema), particularly in relieving itching and reducing trypsin levels.

[0055] In some embodiments, when the product used according to the third aspect of this application is used to improve eczema (e.g., allergic eczema), particularly to relieve itching and reduce trypsin levels, the dosage may be such that the intake of MLCT is 2.25 g to 30 g per day, for example, 2.25, 2.50, 2.75, 3.00, 3.25, 3.50, 3.75, 4.00, 4.25, 4.50, 4.75, 5.00, 5.25, 5.50, 5.75, 6.00, 6.25, 6.50, 6.75, 7.00, 7.25, 7.50, 7.75, 8.00, 8.25, 8.50, 8.75, 9.00, 9.25, 9.50, 9.75, 10.0, 10.5, 11.0, 11.5, 1 2.0, 12.5, 13.0, 13.5, 14.0, 14.5, 15.0, 15.5, 16.0, 16.5, 17.0, 17.5, 18.0, 18.5, 19.0, 19.5, 20.0, 20.5, 21.0, 21.5, 22.0, 22.5, 23.0, 23.5, 24.0, 24.5, 25.0, 25.5, 26.0, 26.5, 27.0, 27.5, 28.0, 28.5, 29.0, 29.5, 30.0 g, or within any two of the above ranges. Furthermore, in a further embodiment, the intake of the MFGM is proportionally converted.

[0056] In some embodiments, the eczema is allergic eczema. In some embodiments, improving the eczema may include relieving itching and / or reducing trypsin levels.

[0057] All descriptions above regarding the compositions described in the first aspect of this application and the products described in the second aspect of this application are applicable here and will not be repeated here.

[0058] Example

[0059] 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.

[0060] The technical solution of this application is explained in more detail through zebrafish animal experiments in the embodiments.

[0061] In all the examples below, the medium- and long-chain fatty acid triglycerides were derived from medium- and long-chain fatty acid edible oils with a purity of 61%, produced by Yihai Kerry Co., Ltd., with production batch number 20250804; MFGM was purchased from Arla, with the product name Lacprodan® MFGM-10 and batch number P510216. The phospholipid content of this raw material was 8±2%, the protein content was 71.5±5% by weight, and the sphingomyelin content was 25±10g / 100g.

[0062] Unless otherwise stated, all reagents used in this embodiment are commercially available or conventional materials.

[0063] Medium- and long-chain triglycerides (MLCT): Derived from medium- and long-chain fatty acid edible oils, with a purity of 61±10%, produced by Yihai Kerry Co., Ltd., with production batch number 20250804.

[0064] Milk fat globule membrane (MFGM): Purchased from Arla, product name Lacprodan® MFGM-10, batch number P510216. The phospholipid content of this raw material is 8±2%, the protein content is 71.5±5% by weight, and the sphingomyelin content is 25±10g per 100g of phospholipid.

[0065] Loratadine tablets, batch number 241203, manufactured by Peking University Medicine Co., Ltd., solvent is DMSO.

[0066] 1-Chloro-2,4-Dinitrobenzene, batch number F2518064, Shanghai Aladdin Biochemical Technology Co., Ltd., China.

[0067] Wild-type AB strain zebrafish: bred and provided by the fish breeding center of Hangzhou Huante Biotechnology Co., Ltd.

[0068] Example 1: Determination of Maximum Tolerated Concentration (MTC) for a Single Sample

[0069] Wild-type AB strain zebrafish, 4 days post-fertilization (4 dpf), were randomly selected and placed in 6-well plates, with 30 zebrafish treated in each well (experimental group). Water-soluble samples were administered (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, each experimental group received water-soluble DNCB to establish a zebrafish eczema model. After treatment at 28℃ for 21 h, except for the normal control group, each experimental group received a high concentration of water-soluble DNCB and continued treatment at 28℃ for another 3 h. The MTC of the samples on the model zebrafish was then measured.

[0070] Table 1. Experimental results for the maximum detectable concentration (n = 30)

[0071]

[0072] Based on the results in Table 1, medium- and long-chain fatty acid triglyceride concentrations below 2000 μg / mL and MFGM concentrations below 500 μg / mL were selected for further study.

[0073] Example 2: Evaluation of the efficacy of the sample in improving eczema - behavioral (pruritus) efficacy.

[0074] Wild-type AB strain zebrafish (4 dpf) 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 loratadine at a concentration of 187.5 ng / mL. A normal control group and a model control group were also included, with a volume of 3 mL per well. Simultaneously with the administration of samples or loratadine, except for the normal control group, each experimental group received water-soluble DNCB to establish a zebrafish eczema model. After treatment at 28℃ for 21 h, except for the normal control group, each experimental group received a second water-soluble high-concentration DNCB treatment at 28℃ for 3 h. Ten zebrafish from each experimental group were then randomly selected and placed in a 96-well plate (1 zebrafish / well, 200 μL / well). Behavioral data were collected for 20 min using a behavior analyzer (Zebra Lab 3.22.3.31, Viewpoint, France). The total movement distance of the zebrafish was analyzed, and the statistical analysis results were used to evaluate the efficacy of the samples in improving eczema. Statistical results are expressed as mean ± SE. Statistical analysis using SPSS software showed that P < 0.05 was statistically significant.

[0075] Following the above method, zebrafish were administered medium- and long-chain fatty acid triglycerides and milk fat globule membranes at different doses to evaluate their effects on behavioral (pruritus) efficacy. The dosages and results are shown in Table 2.

[0076] In Table 2, the parameters are as follows:

[0077] Total movement distance = The total distance the zebrafish moves in 20 minutes, in millimeters (mm);

[0078] Recovery amount = Total movement distance of zebrafish in the model control group – Total movement distance of zebrafish in the formulation group or single-sample comparative group, in mm;

[0079] Synergistic recovery amount = Recovery amount of formulation group – Sum of recovery amounts of single-sample comparative proportions at corresponding concentrations, in mm;

[0080] Synergy coefficient = Recovery amount of formulation group / Sum of recovery amounts of single-sample comparative proportions at corresponding concentrations;

[0081] Unit dose synergy coefficient = synergy coefficient / sum of MLCT and milk fat globule membrane dose.

[0082] Table 2. Results of the experiment evaluating the efficacy of the samples in improving eczema (behavioral (pruritus)).

[0083]

[0084] Note: *P<0.05, **P<0.01, ***P<0.01

[0085] From Table 2 and Figure 1 The results showed that the total movement distance of the model control group was significantly increased compared with that of the normal control group, indicating that the zebrafish eczema model was successfully established by administering DNCB in water.

[0086] Compared with the model control group, the positive control drug (loratadine) and higher concentrations of single-sample milk fat globule membrane (150 μg / mL and 450 μg / mL) both showed efficacy in improving eczema. Specifically, compared with the model control group, the total movement distance (mm) of zebrafish decreased, while single-sample medium- and long-chain fatty acid triglycerides did not show efficacy in improving eczema.

[0087] Compared with the model control group, the total movement distance of the positive control group given loratadine was significantly reduced (recovered), indicating that the pruritus symptoms of the zebrafish model were improved, and thus the eczema condition was improved.

[0088] Compared with the model control group, the control group treated with higher concentrations of milk fat globule membrane (150 μg / mL and 450 μg / mL) showed varying degrees of reduction in total motor distance. However, the single-sample comparison group treated with MLCT alone and with a lower concentration of milk fat globule membrane (50.0 μg / mL) did not show a significant reduction in total motor distance, indicating that treatment with milk fat globule membrane alone, rather than MLCT alone, has the effect of improving eczema. When the dosage of MLCT or milk fat globule membrane was low, the reduction in total motor distance was not significant, indicating that the effect of treating eczema with MLCT alone or milk fat globule membrane alone was relatively weak.

[0089] Compared with the model control group, the total movement distance of the experimental groups using the combination of MLCT and milk fat globule membrane was significantly reduced (P<0.05). For example, the experimental groups given formulas 1 to 7 all showed a significant reduction in total movement distance, indicating that the combination of MLCT and milk fat globule membrane can significantly improve eczema.

[0090] Furthermore, compared to the single-sample control group, the combined use of MLCT and milk fat globule membrane showed a significant synergistic effect. For example, as shown in Table 2, the synergistic recovery amounts of formulation 1 (222 μg / mL MLCT + 50 μg / mL milk fat globule membrane), comparative example 1 (222 μg / mL MLCT), and comparative example 4 (50 μg / mL milk fat globule membrane) reduced the total movement distance by 424 mm, 100 mm, and 151 mm, respectively. The reduction in total movement distance caused by formulation 1 (424 mm) was greater than the sum of the reductions in movement distance caused by comparative examples 1 and 5 (251 mm), indicating a synergistic effect when MLCT and milk fat globule membrane are used in combination. Similarly, formulations 2 to 7 also showed a synergistic effect. Therefore, when MLCT and milk fat globule membrane are used in combination at a mass ratio ranging from 0.493 to 40:1, they show a synergistic effect in improving eczema.

[0091] On the other hand, synergistic effects can also be characterized by a synergistic coefficient, where a synergistic coefficient greater than 1 indicates a synergistic effect. Calculations show that the synergistic coefficient for formula 1 is 1.6892 > 1, indicating a synergistic effect between MLCT and milk fat globule membrane, which can synergistically reduce the total movement distance (mm), thus indicating that the combination of the two can synergistically improve eczema. Similarly, the synergistic coefficients for formulas 2 to 7 are also greater than 1, also indicating a synergistic effect between MLCT and milk fat globule membrane, which can synergistically reduce the total movement distance (mm) and thus synergistically improve eczema. In other words, formulas 1-7 with an MLCT:milk fat globule membrane mass ratio of 0.493-40:1 have a synergistic effect in improving eczema (synergistic coefficients are all greater than 1).

[0092] On the other hand, in terms of the unit dose synergistic coefficient, Formula 1 > Formula 2 > Formula 3 = Formula 4 > Formula 5 > Formula 6 > Formula 7. Preferably, when the preferred mass ratio of MLCT: milk fat globule membrane in improving eczema efficacy is 1.48-4.44:1 (unit dose synergistic coefficient greater than 0.0020), it has a better synergistic effect in improving eczema (itching).

[0093] Example 3: Efficacy of Samples in Improving Eczema - Evaluation of Trypsin Activity Level

[0094] Wild-type AB strain zebrafish with a 4-day pf growth rate 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 3) were administered, with loratadine at a positive control concentration of 187.5 ng / mL. A normal control group and a model control group were also included, with a volume of 3 mL per well. Three replicate experiments were conducted, with 90 zebrafish per replicate. While administering samples or loratadine, all experimental groups, except the normal control group, received water-soluble DNCB to establish a zebrafish eczema model. After treatment at 28℃ for 21 h, all experimental groups, except the normal control group, received a second water-soluble high-concentration DNCB treatment at 28℃ for 3 h. Zebrafish samples from each experimental group were collected according to the trypsin-like protein kit (catalog number ml286418V, Shanghai Enzyme-Link Biotechnology Co., Ltd., China). Data were collected using a multi-functional microplate reader (SPARK, TECAN, Austria) and the trypsin content in each zebrafish group was analyzed. The statistical analysis results of this index (trypsin content) were used to evaluate the efficacy of the samples in improving eczema. Statistical results are expressed as mean ± SE. Statistical analysis was performed using SPSS software; P < 0.05 indicated statistical significance.

[0095] Following the above method, zebrafish were administered medium- and long-chain fatty acid triglycerides and milk fat globule membrane at different dosages to evaluate the efficacy of the two single components in improving trypsin-like activity levels. The dosages and results are shown in Table 3.

[0096] In Table 3, the parameters are as follows:

[0097] Trypsin content = Trypsin content in zebrafish model, in ng / mg prot;

[0098] Recovery amount = Trypsin content in zebrafish of the model control group – Trypsin content in zebrafish of the formulation group or single-sample comparative group, in units of (ng / mg prot);

[0099] Synergistic recovery amount = recovery amount of formulation group – sum of recovery amounts of single-sample comparative proportions at corresponding concentrations, in units of (ng / mg prot);

[0100] Synergy coefficient = Recovery amount of formulation group / Sum of recovery amounts of single-sample comparative proportions at corresponding concentrations;

[0101] Unit dose synergy coefficient = synergy coefficient / sum of MLCT and milk fat globule membrane dose.

[0102] Table 3. Evaluation results of the samples' efficacy in improving eczema (trypsin activity level) (n = 10)

[0103]

[0104] Note: *P<0.05, **P<0.01, ***P<0.01

[0105] As shown in Table 3, compared with the normal control group, the trypsin content in the model control group was significantly increased, indicating that the zebrafish eczema model was successfully established by administering DNCB in water.

[0106] Compared with the model control group, the trypsin content in the positive control group given loratadine was significantly reduced, indicating that the eczema condition in the zebrafish model was improved.

[0107] Compared with the model control group, the control group treated with higher concentrations of milk fat globule membrane (150 μg / mL and 450 μg / mL) showed varying degrees of decrease in trypsin levels (ng / mgprot). However, the single-sample comparison of treatment with MLCT alone and lower concentrations of milk fat globule membrane (50.0 μg / mL) did not show a significant decrease in trypsin levels, indicating that treatment with milk fat globule membrane alone, rather than MLCT alone, has the effect of improving eczema. When the dosage of MLCT or milk fat globule membrane was low, the decrease in trypsin levels was not significant, indicating that the effect of treatment with MLCT or milk fat globule membrane alone on improving eczema was relatively weak.

[0108] Compared with the model control group, the trypsin levels in the experimental groups using the combination of MLCT and milk fat globule membrane were significantly reduced (P<0.05). For example, the experimental groups given formulations 1 to 7 all showed a significant reduction in trypsin levels, indicating that the combination of MLCT and milk fat globule membrane can significantly improve eczema.

[0109] Furthermore, compared to the single-sample control group, the combined use of MLCT and milk fat globule membrane showed a significant synergistic effect. For example, as shown in Table 3, the synergistic recovery amounts of formulation 1 (222 μg / mL MLCT + 50 μg / mL milk fat globule membrane), comparative example 1 (222 μg / mL MLCT), and comparative example 4 (50 μg / mL milk fat globule membrane) reduced trypsin levels (ng / mgprot) by 0.35 ng / mgprot, 0.08 ng / mgprot, and 0.03 ng / mgprot, respectively. The reduction in trypsin levels caused by formulation 1 (0.35 ng / mgprot) was greater than the sum of the reductions in trypsin levels caused by comparative examples 1 and 5 (0.11 ng / mgprot), indicating a synergistic effect when MLCT and milk fat globule membrane are used in combination. Similarly, formulations 2 to 7 also showed a synergistic effect. Therefore, when MLCT is used in combination with milk fat globule membrane at a mass ratio in the range of 0.493-40:1, it shows a synergistic effect in improving eczema.

[0110] On the other hand, synergistic effects can also be characterized by a synergistic coefficient, where a synergistic coefficient greater than 1 indicates a synergistic effect. Calculations show that the synergistic coefficient for formula 1 is 3.1818 > 1, indicating a synergistic effect between MLCT and milk fat globule membrane, which can synergistically reduce trypsin levels (ng / mgprot), thus demonstrating that the combination of the two can synergistically improve eczema. Similarly, the synergistic coefficients for formulas 2 to 7 are also greater than 1, confirming a synergistic effect between MLCT and milk fat globule membrane, which can synergistically reduce trypsin levels (ng / mgprot) and thus synergistically improve eczema. In other words, formulas 1-7 with an MLCT:milk fat globule membrane mass ratio of 0.493-40:1 have a synergistic effect in improving eczema (synergistic coefficients are all greater than 1).

[0111] 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 the composition in the preparation of a product for improving eczema, characterized in that, The composition comprises medium- and long-chain fatty acid triglycerides (MLCT) and milk fat globule membranes (MFGM) in a mass ratio of 0.4:1 to 40:

1.

2. The use according to claim 1, characterized in that, The eczema described is allergic eczema.

3. The use according to claim 1 or 2, characterized in that, The mass ratio of MLCT to MFGM ranges from 1:1 to 40:

1.

4. The use according to claim 1 or 2, characterized in that, The mass ratio of MLCT to MFGM is 1:1 to 5:

1.

5. The use according to claim 1 or 2, characterized in that, Improving eczema includes preventing eczema or relieving one or more symptoms of eczema.

6. The use according to claim 1 or 2, characterized in that, The improvement of eczema includes relieving itching and reducing trypsin levels, or one or more of these.

7. The use according to claim 1 or 2, characterized in that, The product is used in such a dosage that the intake of medium- and long-chain fatty acid triglycerides is 2.25 g to 30.0 g per day.

8. The use of the composition in the preparation of a medicament for improving eczema, characterized in that, The composition comprises medium- and long-chain fatty acid triglycerides (MLCT) and milk fat globule membranes (MFGM) in a mass ratio of 0.4:1 to 40:

1.

9. The use according to claim 8, characterized in that, The eczema described is allergic eczema.

10. The use according to claim 8 or 9, characterized in that, The mass ratio of MLCT to MFGM ranges from 1:1 to 40:

1.

11. The use according to claim 8 or 9, characterized in that, The mass ratio of MLCT to MFGM is 1:1 to 5:

1.

12. The use according to claim 8 or 9, characterized in that, Improving eczema includes preventing eczema or relieving one or more symptoms of eczema.

13. The use according to claim 8 or 9, characterized in that, The improvement of eczema includes relieving itching and reducing trypsin levels, or one or more of these.

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