Composition for improving barrier function and application thereof

Abstract

The invention provides a composition for improving a barrier function and application thereof, and relates to the technical field of cell injury nursing. Gamma-aminobutyric acid (GABA) and cordyceps militaris fermentation filtrate (FCM) are used for treating barrier damage for the first time. Specifically, the combination of the gamma-aminobutyric acid and the cordyceps militaris fermentation filtrate can significantly improve damage of an epithelial mechanical barrier and an immune barrier caused by external stimulation, so that the epithelial barrier function can be prevented and improved from multiple dimensions.

Description

Technical Field

[0001] This application relates to the field of cell damage care technology, and more particularly to a composition for improving barrier function and its application. Background Technology

[0002] In daily life, people are affected by potential hazards in the external environment. The epithelial barrier, formed by epithelial tissue, plays a physical, chemical, biological, and immune defensive role between the body's internal and external environments. It is the body's first line of defense against harmful external substances (such as pathogens, toxins, and allergens) and prevents the loss of water and nutrients. Compared with the skin, the epithelial barrier of the inner surfaces of body cavities that communicate with the outside world (respiratory tract, digestive tract, urinary and reproductive tracts) has histological differences such as the lack of a granular layer and stratum corneum, incomplete keratinization, and weaker intercellular junctions. This makes it easier for microorganisms to damage tissues and even enter the body's fluid system, inducing health problems.

[0003] Improving the function of the human epithelial barrier, especially the function of the coelomic epithelial barrier, is of vital importance to human health. Summary of the Invention

[0004] After in-depth research, the inventors of this application discovered that the use of γ-aminobutyric acid and Cordyceps militaris fermentation filtrate at a mass ratio of 1:(0.01-8) can produce a synergistic effect in preventing and / or improving epithelial mechanical barrier function and epithelial immune barrier function, thus proving that the combination can be used to improve barrier function.

[0005] On the one hand, this application provides a composition for improving barrier function, the composition comprising γ-aminobutyric acid and Cordyceps militaris fermentation filtrate in a physiologically acceptable medium, wherein the mass ratio of γ-aminobutyric acid to Cordyceps militaris fermentation filtrate is 1:(0.01-8).

[0006] The mass ratio of γ-aminobutyric acid to Cordyceps militaris fermentation broth can be any value or range of 1:0.01, 1:0.02, 1:0.03, 1:0.04, 1:0.05, 1:0.06, 1:0.07, 1:0.08, 1:0.09, 1:0.1, 1:0.2, 1:0.3, 1:0.4, 1:0.5, 1:0.6, 1:0.7, 1:0.8, 1:0.9, 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, or 1:8.

[0007] Those skilled in the art can adjust the specific concentrations of γ-aminobutyric acid and Cordyceps militaris fermentation liquid in the product according to the actual situation, and this application does not make specific limitations on this.

[0008] In a preferred embodiment, the concentration of γ-aminobutyric acid in the product, by mass percentage, can be 0.001%-5%, for example, it can be any value or range of 0.001%, 0.002%, 0.003%, 0.004%, 0.005%, 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%.

[0009] In a preferred embodiment, the concentration of Cordyceps militaris fermentation liquid in the product, by mass percentage, can be 0.01%-10%, for example, any value or range of 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 5.5%, 6%, 6.5%, 7%, 7.5%, 8%, 8.5%, 9%, 9.5%, 10%.

[0010] The Cordyceps militaris fermentation filtrate contains high levels of cordycepin and cordycepic acid.

[0011] Furthermore, the cordycepin content in the Cordyceps militaris fermentation filtrate is above 40 mg / L, preferably 40-200 mg / L, and more preferably 80-200 mg / L.

[0012] Furthermore, the cordycepic acid content in the Cordyceps militaris fermentation filtrate is above 5 g / L, preferably 5-30 g / L.

[0013] In some specific embodiments, the Cordyceps militaris fermentation filtrate is obtained by fermenting Cordyceps militaris with lactic acid bacteria.

[0014] Furthermore, the Cordyceps militaris fermentation filtrate can be prepared using the method described in Chinese Patent CN111808901A.

[0015] In a preferred embodiment, the method for preparing the Cordyceps militaris fermentation filtrate includes: fermenting lactic acid bacteria in a fermentation medium with Cordyceps militaris as the nitrogen source to obtain Cordyceps militaris fermentation extract.

[0016] Furthermore, the fermentation medium using Cordyceps militaris as a nitrogen source comprises the following components: 5-10 g / L Cordyceps militaris powder, 5 g / L glucose, 15-20 g / L fructose, 3-8 g / L sodium acetate, 1-3 g / L magnesium sulfate, and water as the remainder.

[0017] Furthermore, in addition to the fermentation step, it may also include a step of further processing the fermentation broth, including but not limited to one or more of the following operations: pH adjustment, filtration, sterilization, protein removal, concentration, and drying.

[0018] Furthermore, the above preparation method specifically includes the following steps:

[0019] (1) Culture lactic acid bacteria in seed culture to obtain seed solution;

[0020] (2) Inoculate the seed liquid into a fermentation medium with Cordyceps militaris as the nitrogen source, aerate and stir, and ferment until there is no residual sugar to end the fermentation and obtain the fermentation liquid;

[0021] (3) The fermentation liquid was processed to obtain Cordyceps militaris fermentation extract.

[0022] Furthermore, the Cordyceps militaris powder refers to the powder made from the natural fruiting bodies of Cordyceps militaris after drying and pulverizing. There are no special requirements for the particle size of the powder, which is generally 40 mesh or less.

[0023] Furthermore, among the various lactic acid bacteria varieties disclosed in the prior art, such as Lactobacillus, Leuconostoc mesenteroides, and Bifidobacterium, Lactobacillus is preferred.

[0024] Furthermore, in step (1), the lactic acid bacteria can select suitable seed culture medium and seed culture conditions from the publicly available prior art to obtain the seed liquid required for fermentation culture. The seed culture conditions, such as temperature and pH, can be selected to be the most suitable conditions for each strain.

[0025] Further, in step (2), the seed liquid is inoculated into the fermentation medium with Cordyceps militaris as the nitrogen source at an inoculation rate of 5-10% for fermentation. The pH value is not controlled during fermentation, and fermentation is terminated when the residual sugar is exhausted. The fermentation temperature and pH are the optimal temperature and pH for each strain. For example, the fermentation temperature of lactic acid bacteria is maintained at about 37℃ and the pH is maintained at about 6.2-6.6. Aeration and stirring are carried out during the culture process, and the aeration rate is 0.3-0.6 vvm.

[0026] Furthermore, in step (3), after fermentation, the fermentation liquid is subjected to heating sterilization, pH adjustment and filtration in sequence to obtain Cordyceps militaris fermentation extract.

[0027] In some specific embodiments, the Cordyceps militaris fermentation filtrate is obtained by fermenting Cordyceps militaris with Leuconostocsp.

[0028] The Cordyceps militaris fermentation filtrate was obtained by fermenting Cordyceps militaris with Leuconostoc sp. HX-236.

[0029] Furthermore, the preservation number of the Leuconostoc sp. HX-236 is CCTCCNO: M20221389.

[0030] The Cordyceps militaris fermentation filtrate can be prepared using the method described in Chinese Patent CN 116496926 A.

[0031] In a preferred embodiment, the method for preparing the Cordyceps militaris fermentation filtrate includes:

[0032] The step of fermenting Cordyceps militaris with Leuconostoc sp. HX-236, the product of which is Cordyceps militaris fermentation product, the preservation number of Leuconostoc sp. HX-236 is CCTCC NO: M20221389.

[0033] Furthermore, in addition to the fermentation step, it may also include a step of further processing the fermentation broth, including but not limited to one or more of the following operations: pH adjustment, filtration, sterilization, protein removal, concentration, and drying.

[0034] Furthermore, in the above preparation method, the culture medium used for fermentation is composed of carbon source, nitrogen source, inorganic salt, water and other components. The carbon source can be sugars such as glucose and fructose, the nitrogen source can be Cordyceps militaris powder, and the inorganic salt can be sodium acetate, magnesium sulfate and other components.

[0035] Furthermore, in the above preparation method, Cordyceps militaris is selected as the nitrogen source for the fermentation culture medium.

[0036] In a specific embodiment of the present invention, the fermentation medium formula adopts the medium formula disclosed in CN111808901A.

[0037] Furthermore, the fermentation medium using Cordyceps militaris as a nitrogen source comprises the following components: Cordyceps militaris powder 5-10 g / L, glucose 5 g / L, fructose 15-20 g / L, sodium acetate 3-8 g / L, magnesium sulfate 1-3 g / L, and water as the remainder.

[0038] Furthermore, in the above preparation method, the optimal culture temperature for Leuconostoc mesenteroides HX-236 is 35-38℃.

[0039] In a specific embodiment of the present invention, the fermentation process includes: inoculating Leuconostoc mesenteroides HX-236 seed culture into a fermentation medium, culturing with aeration and stirring at 35-38°C, without controlling the pH value during the fermentation process, and ending the fermentation when there is no residual sugar to obtain the fermentation broth.

[0040] Furthermore, the seed culture of Leuconostoc mesenteroides HX-236 can be obtained by culturing Leuconostoc mesenteroides HX-236 in liquid MRS medium at a temperature of 35-38℃ and a pH of 6.2-6.6.

[0041] In a preferred embodiment, the Cordyceps militaris fermentation filtrate is obtained by fermenting Cordyceps militaris with Leuconostocsp.

[0042] Those skilled in the art can prepare or purchase the above-mentioned Cordyceps militaris fermentation filtrate according to actual conditions.

[0043] Furthermore, the physiologically acceptable medium includes one or more of solvents, pH adjusters, preservatives, and thickeners.

[0044] This application may also include other functional ingredients that do not negatively affect the barrier function, such as hyaluronic acid.

[0045] This application may also add physiologically acceptable excipients, which may be suitable propellants, solubilizers, cosolvents, emulsifiers, colorants, binders, disintegrants, fillers, lubricants, wetting agents, osmotic pressure regulators, stabilizers, flow aids, flavoring agents, suspending agents, coating materials, fragrances, anti-adhesion agents, binding agents, penetration enhancers, buffers, plasticizers, surfactants, foaming agents, defoamers, encapsulating agents, humectants, absorbents, diluents, flocculants and anti-flocculation agents, filter aids, release inhibitors, etc.

[0046] The compositions of this application can be prepared by common methods.

[0047] In a preferred embodiment, the method includes dissolving γ-aminobutyric acid and Cordyceps militaris fermentation filtrate in a solvent and mixing them thoroughly.

[0048] One aspect of this application relates to compositions, which are any compositions capable of achieving the effects described in this application. The compositions include, but are not limited to, the simultaneous or sequential use of the components. "Simultaneous use" includes using them together in the same formulation or separately in different formulations. "Sequential use" includes using them sequentially in different formulations, with no restriction on the order of sequential use.

[0049] On the other hand, this application also provides the use of the described composition in the preparation of products for preventing and / or improving epithelial barrier function impairment.

[0050] Furthermore, the epithelial barrier includes a coelomic epithelial barrier.

[0051] Preferably, the epithelial barrier includes the reproductive tract epithelial barrier, the oral cavity epithelial barrier, the esophageal epithelial barrier, and / or the gastrointestinal tract epithelial barrier.

[0052] Preferably, the epithelial barrier is a reproductive tract epithelial barrier.

[0053] Furthermore, the epithelial barrier function includes the epithelial mechanical barrier function and / or the epithelial immune barrier function.

[0054] Preferably, the epithelial mechanical barrier function includes mitigating increased cell permeability and / or repairing cell barrier damage.

[0055] The relative permeability of the vaginal epithelial cell layer can be less than 126%; preferably 100%-125.1%.

[0056] Preferably, the epithelial immune barrier function includes preventing and / or alleviating inflammatory responses, reducing inflammatory factor levels, and inhibiting inflammatory factor secretion; more preferably, the inflammatory factor is IL6.

[0057] On the other hand, this application also provides the use of Cordyceps militaris fermentation filtrate in the preparation of products for preventing and / or improving epithelial barrier function damage.

[0058] The epithelial barrier is described as above.

[0059] On the other hand, this application also provides a barrier care product, which includes at least the above-described composition.

[0060] Furthermore, the product is in liquid, gel, or solid form.

[0061] Furthermore, the product may be for internal and / or external use.

[0062] More preferably, it can be administered orally and / or topically.

[0063] The present invention has the following beneficial effects:

[0064] This application is the first to discover that Cordyceps militaris fermentation filtrate can improve epithelial mechanical barrier function and epithelial immune barrier function.

[0065] Furthermore, the combination of γ-aminobutyric acid and Cordyceps militaris fermentation filtrate achieves effects comparable to or even better than single components in improving epithelial mechanical and immune barrier damage caused by external stimuli, playing a synergistic role and thus preventing and improving epithelial barrier function damage from multiple dimensions. Detailed Implementation

[0066] To more clearly illustrate the overall concept of this application, a detailed description is provided below by way of embodiments. Numerous specific details are set forth in the following description to provide a more thorough understanding of the invention. However, it will be apparent to those skilled in the art that the invention can be practiced without one or more of these details. In other instances, certain technical features well-known in the art have not been described to avoid confusion with the invention.

[0067] Before further describing specific embodiments of the present invention, it should be understood that the scope of protection of the present invention is not limited to the specific embodiments described below; it should also be understood that the terminology used in the embodiments of the present invention is for describing specific embodiments and not for limiting the scope of protection of the present invention. Test methods in the following embodiments that do not specify specific conditions are generally performed under conventional conditions or as recommended by the respective manufacturers.

[0068] It should be noted that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to limit the exemplary embodiments according to this application. As used herein, the singular form is intended to include the plural form as well, unless the context clearly indicates otherwise. Furthermore, it should be understood that when the terms "comprising" and / or "including" are used in this specification, they indicate the presence of features, steps, operations, devices, components, and / or combinations thereof.

[0069] When numerical ranges are given in the embodiments, it should be understood that, unless otherwise stated in the present invention, both endpoints of each numerical range and any value between the two endpoints may be selected. Unless otherwise defined, all technical and scientific terms used in this invention have the same meaning as commonly understood by one of ordinary skill in the art. In addition to the specific methods, apparatus, and materials used in the embodiments, based on the knowledge of the prior art possessed by one of ordinary skill in the art and the description of this invention, any prior art methods, apparatus, and materials similar to or equivalent to those described, apparatus, and materials in the embodiments of this invention may be used to implement the present invention.

[0070] Unless otherwise specified, in the following embodiments, reagents or instruments whose manufacturers are not indicated are all conventional products that can be purchased commercially.

[0071] Unless otherwise stated, the experimental methods, detection methods, and preparation methods disclosed in this invention all employ conventional techniques in the fields of microbiology, biochemistry, analytical chemistry, cell culture, and related areas.

[0072] In addition, the "water" mentioned in this invention includes any feasible water that can be used in the art, such as deionized water, distilled water, ion-exchanged water, double-distilled water, high-purity water, and purified water.

[0073] In the following examples, unless otherwise specified, % means wt%, i.e., weight percentage.

[0074] Among them, LPS lipopolysaccharide (PAO1-LPS) was purchased from FUJIFILM, catalog number: 129-05961; γ-aminobutyric acid was purchased from Bloomage Biotechnology Co., Ltd., CAS number: 56-12-2, hereinafter referred to as GABA; Cordyceps militaris fermentation broth was purchased from Bloomage Biotechnology Co., Ltd., trade name: Bioyouth TM FCM, catalog number LOT: 1091031, hereinafter referred to as FCM; Cordyceps militaris extract was purchased from Shanghai Siyan Biotechnology Co., Ltd., hereinafter referred to as CM; Hyaluronic acid (HA) was purchased from Bloomage Biotechnology Co., Ltd., trade name: Hybloom TM Micro True TM Catalog number LOT: 20201012-1, molecular weight: 800-1000 Da; DMEM medium was purchased from Gibco, catalog number: 10569010; IL6 ELISA kit was purchased from Linko Biotech, catalog number EK106; human vaginal epithelial cells VK2 / E6E7 were purchased from ATCC#CRL2616.

[0075] Experimental Example 1

[0076] This study investigated the effects of GABA, FCM, CM, HA, and their combinations on vaginal epithelial barrier function under LPS stimulation. Cell permeability between cells was reflected by indicators such as FD4 (fluorescein isothiocyanate dextran, FITC-labeled dextran) molecular transport, thereby reflecting the mechanical barrier function.

[0077] 1. Sample preparation

[0078] (1) The blank group sample was VK2 / E6E7 cell complete culture medium (DMEM containing 10% fetal bovine serum (FBS) and 1% penicillin and streptomycin);

[0079] (2) The control group sample was VK2 / E6E7 cell complete culture medium containing PAO1-LPS (10 μg / mL);

[0080] (3) Samples for Examples and Comparative Examples: Each raw material (γ-aminobutyric acid (GABA), Cordyceps militaris fermentation broth (FCM), Cordyceps militaris extract (CM), and hyaluronic acid (HA)) was weighed and dissolved in culture medium to obtain a mother liquor. The mother liquor was diluted 20 times and mixed according to the composition concentration ratio for subsequent experiments. The specific composition and concentration are shown in Table 1. The culture medium was a complete VK2 / E6E7 cell culture medium containing PAO1-LPS (10 μg / mL).

[0081] Table 1

[0082]

[0083] 2. Cytological testing

[0084] VK2 / E6E7 cells were cultured in DMEM medium in a Transwell system for 4 days to simulate the vaginal epithelial cell layer. Test samples (blank, control, example, and comparative samples) prepared above were added and cultured for 24 h. Then, FD4 molecules (FITC-labeled dextran, final surface concentration 1 mg / mL, Sigma, catalog number 60842-46-8) were added and cultured further. After another 2 h of culture, the culture medium was recovered, and 100 μL / well was inoculated into 96-well plates, with 3 replicates per group. An additional 100 μL of culture medium was used as a background fluorescence control; the fluorometer reading was recorded as F0. The fluorescence intensity value F1 was obtained by measuring FITC (excitation, 492 nm; emission, 520 nm) in the fluorometer, with the blank group as the cutoff control and its fluorescence value recorded as C. FD4 molecule transport was measured to assess barrier function; three measurements were performed as biological replicates, and the overall data were averaged for calculation. The barrier function is strongly negatively correlated with FD4 permeability. The FD4 permeability is calculated by measuring the fluorescence intensity in the receiving chamber with a fluorescence spectrophotometer and then calculating the permeability.

[0085] FD4 permeability = (recovered fluorescence intensity F1 - background fluorescence intensity F0) / (blank group fluorescence intensity C - background fluorescence intensity F0) × 100%. (References: Oami T, Coopersmith CM. Measurement of Intestinal Permeability During Sepsis. Methods Mol Biol. 2021, 2321:169-175. Jiang Y, Song J, Xu Y, et al. Piezo1 regulates intestinal epithelial function by affecting the tight junction protein claudin-1 via the ROCK pathway. Life Sci. 2021, 275:119254.)

[0086] The molecular transport permeability data of FD4 were statistically analyzed using a two-tailed paired T-test. The results are shown in Table 2. In Table 2, * indicates p<0.05, ** indicates p<0.01, and *** indicates p<0.001.

[0087] Table 2 Effect of the composition on the permeability of VK2 / E6E7 cells

[0088]

[0089] As shown in Table 2, the permeability of the control group was significantly increased compared with that of the blank group (P<0.001), with a relative permeability of 176.1%. The higher the permeability, the deeper the barrier damage, proving that the treatment of cells with PAO1-LPS can simulate barrier damage.

[0090] The results of the examples were significantly different from those of the control group, indicating that the samples of the examples all had the effect of alleviating the increase in cell permeability and improving barrier function.

[0091] The statistical difference between Example 1 and Example 8 indicates that the combination of γ-aminobutyric acid (GABA) and Cordyceps militaris fermentation broth (FCM) in Example 1 can still achieve the same effect as when the amount of GABA is high, even with a reduced amount of GABA. This demonstrates that γ-aminobutyric acid (GABA) and Cordyceps militaris fermentation broth (FCM) have a synergistic effect in repairing cell barrier damage.

[0092] Examples 2-5 showed statistically significant differences compared to Examples 7 and 8, indicating that the combination of γ-aminobutyric acid (GABA) and Cordyceps militaris fermentation broth (FCM) was more effective in improving barrier function than adding either GABA or FCM alone. This demonstrates that GABA and FCM have a synergistic effect in repairing damaged cell barriers.

[0093] Compared with Examples 7 and 8 or Comparative Example 1, Comparative Examples 2, 3, and 5 not only did not produce a better effect on improving barrier function, but even weakened its effect, indicating that not every combination of substances that can improve barrier function can bring about a synergistic effect on improving barrier function.

[0094] Example 8 also showed a statistically significant difference compared to Comparative Example 1, indicating that Cordyceps militaris ferment broth (FCM) is more effective in improving barrier function than Cordyceps militaris extract (CM). In summary, this demonstrates that Cordyceps militaris ferment broth (FCM) has stronger biological efficacy compared to Cordyceps militaris extract (CM).

[0095] Based on the data from Examples 4 and 6 above, the addition of conventional active ingredients does not affect the synergistic effect of the composition.

[0096] Experimental Example 2

[0097] Following the experimental results in Example 1, which showed that the composition of Example 3 exhibited the best barrier repair effect, this experiment further investigated the effects of γ-aminobutyric acid (GABA) and Cordyceps militaris ferment broth (FCM) on the secretion of inflammatory factors stimulated by PAO1-LPS, thereby reflecting the function of the epithelial immune barrier.

[0098] The blank group samples, control group samples, and test samples of Examples 3, 7, and 8, as well as Comparative Examples 1 and 2, were prepared using the method of Example 1.

[0099] Human vaginal epithelial cells (VK2 / E6E7) were cultured in 24-well plates for 24 hours until complete adhesion. Afterward, samples from each group were added and treated for another 24 hours. The cell culture supernatant was then collected. The absorbance at 430 nm and 570 nm was measured using enzyme-linked immunosorbent assay (ELISA), and the OD was calculated based on the measured absorbance values. 430 -OD 570 The difference was substituted into the IL6 test kit used (brand: Linko Biotechnology, catalog number: EK106) and passed through the standard curve (y = 0.0158x + 0.0252, where x is the IL6 secretion value and y is the OD value). 430 -OD 570 The concentration of the inflammatory factor IL-6 was calculated by fitting the difference (Reference: Cedrone E, Potter TM, Neun BW, et al. Multiplex Enzyme-Linked Immunosorbent Assay (ELISA) for Detection of Human Cytokines in Culture Supernatants: Version 1. In: National Cancer Institute's Nanotechnology Characterization Laboratory Assay Cascade Protocols. Bethesda (MD): National Cancer Institute (US); 2020.).

[0100] The results are shown in Table 3. Statistical analysis was performed on the data. In Table 3, * indicates p<0.05, ** indicates p<0.01, and *** indicates p<0.001.

[0101] Table 3

[0102]

[0103] The results are shown in Table 3. The IL-6 secretion in the control group was significantly increased compared with that in the blank group (P<0.0001), with a relative increase of 97.07%, proving that this method can simulate the occurrence of vaginal epithelial cell inflammation.

[0104] Examples 3, 7, and 8 all significantly reduced IL-6 secretion compared to the control group, indicating that the addition of γ-aminobutyric acid (GABA) and / or Cordyceps militaris ferment broth (FCM) can, to some extent, improve the vaginal epithelial cell inflammation state induced by PAO1-LPS. Furthermore, Example 3 also significantly reduced IL-6 secretion compared to Examples 7 and 8, demonstrating that the combination of γ-aminobutyric acid (GABA) and Cordyceps militaris ferment broth (FCM) can synergistically inhibit the secretion of inflammatory factors under external stimuli.

[0105] Compared with the control group, Comparative Examples 1 and 2 did not show any effect in inhibiting the secretion of inflammatory factors, indicating that not every combination of substances can inhibit the secretion of inflammatory factors. In summary, this demonstrates that Cordyceps militaris ferment broth (FCM) and Cordyceps militaris extract (CM) have stronger epithelial immune barrier efficacy.

[0106] The above description is merely an embodiment of this application and is not intended to limit the scope of this application. Various modifications and variations can be made to this application by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of this application should be included within the scope of the claims of this application.

Claims

1. A composition for enhancing barrier function, characterized in that, The composition comprises γ-aminobutyric acid and Cordyceps militaris fermentation filtrate in a physiologically acceptable medium, wherein the mass ratio of γ-aminobutyric acid to Cordyceps militaris fermentation filtrate is 1:(0.01-8).

2. The use of the composition of claim 1 in the preparation of products for preventing and / or improving epithelial barrier function impairment.

3. The application according to claim 2, characterized in that, The epithelial barrier includes the coelomic epithelial barrier.

4. The application according to claim 3, characterized in that, The epithelial barriers include the reproductive tract epithelial barrier, the oral cavity epithelial barrier, the esophageal epithelial barrier, and / or the gastrointestinal tract epithelial barrier.

5. The application according to any one of claims 2-4, characterized in that, The epithelial barrier function includes the epithelial mechanical barrier function and / or the epithelial immune barrier function.

6. Application of Cordyceps militaris fermentation filtrate in the preparation of products for preventing and / or improving epithelial barrier function damage.

7. The application according to claim 6, characterized in that, The epithelial barrier includes the coelomic epithelial barrier.

8. The application according to claim 7, characterized in that, The epithelial barriers include the reproductive tract epithelial barrier, the oral cavity epithelial barrier, the esophageal epithelial barrier, and / or the gastrointestinal tract epithelial barrier.

9. The application according to any one of claims 6-8, characterized in that, The epithelial barrier function includes the epithelial mechanical barrier function and / or the epithelial immune barrier function.

10. A barrier care product, characterized in that, The product comprises at least the composition of claim 1.

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