Use of a composition for the manufacture of a product for improving cognitive impairment associated with aging

Abstract

The application relates to the field of biotechnology, and particularly discloses application of a composition in preparation of a product for improving senile cognitive impairment. The application research finds that after a composition formed by combining Lactobacillus plantarum HEAL9, oat green extract and sialic acid in a specific ratio is applied, senile cognitive impairment can be significantly improved, so that the application of the composition in preparation of the product for improving senile cognitive impairment is provided, the composition comprises Lactobacillus plantarum HEAL9, oat green extract and sialic acid in a mass ratio of 1: (0.7-15): (0.5-10). The application provides a new method for improving senile cognitive impairment, and is expected to improve the life quality of the related middle-aged and old population.

Description

Technical Field

[0001] This invention relates to the field of biotechnology, and more specifically, to the use of a composition in the preparation of products for improving age-related cognitive impairment. Background Technology

[0002] Cognitive impairment among middle-aged and elderly people is receiving increasing attention, closely related to factors such as accelerated aging and cognitive decline induced by modern lifestyles like sleep deprivation. As people age, some gradually experience decreased attention, memory loss, and impaired executive function, which can even develop into cognitive impairment in severe cases. This not only significantly reduces quality of life but also places a heavy burden on families and society. Therefore, developing safe, long-term edible products that can effectively delay or improve aging and cognitive impairment is of great significance.

[0003] Oat green extract is an extract from the young, tender plants of oats in their early growth stage, specifically from immature, still green oats (Latin name: Oat 'green oat'). Avena sativa L. This product, derived from the whole plant (aerial parts – stems and leaves) of the oat family (Poaceae), is processed using 30% ethanol extraction, concentration, drying, and grinding to extract its active ingredients. It is rich in dietary fiber, beta-glucan, polyphenolic compounds, and various vitamins and minerals. Studies show it helps improve attention, working memory, and executive function, and also has a certain mood-regulating effect.

[0004] Sialic acid (SA) is a nonose monosaccharide and a component of gangliosides and glycoproteins, participating in synapse formation and neurotransmission. Breast milk is rich in sialic acid, and its mechanism of action is well-defined. It is crucial during the rapid brain development period of infants and young children, indirectly supporting neural development by influencing the expression of genes related to learning and memory. Current research largely focuses on infant brain development.

[0005] HEAL9 is a strain of *Lactobacillus plantarum* that not only improves gut microbiota balance by regulating gut microbiota structure, but also influences cognitive performance through the gut-brain axis pathway. Previous studies have shown that this strain can reduce central inflammatory responses and help improve sleep quality and mood.

[0006] However, despite existing research on the aforementioned raw materials in areas such as brain development, current technologies still have significant shortcomings: First, most studies and products target infants and adolescents, with limited systematic research on middle-aged and elderly individuals exhibiting cognitive decline. Second, past research and commercially available brain health nutritional products often use common raw materials such as phosphatidylserine, theanine, and nervonic acid, typically as single-ingredient supplements or empirically combined formulations. Third, existing multi-component formulations lack clear definitions regarding the dosage and proportion of each functional component, and their efficacy evaluations are often limited to single cognitive behaviors or single aging-related indicators. They lack a systematic design that comprehensively assesses both aging levels and cognitive function status using models that combine behavioral indicators (such as blue proportions) and biochemical indicators (such as telomerase activity and β-galactosidase activity). Therefore, for populations characterized primarily by aging and cognitive impairment, it remains necessary to provide a formulation with clearly defined composition and proportions, validated by the aforementioned multi-dimensional indicators, capable of simultaneously improving both aging and cognitive impairment, to further enhance the improvement effect on aging-related cognitive impairment. Summary of the Invention

[0007] One of the objectives of this invention is to provide a new method that can effectively improve cognitive impairment associated with aging.

[0008] The present invention provides an application of a composition in the preparation of a product for improving age-related cognitive impairment, wherein the composition comprises *Lactobacillus plantarum* HEAL9, oat extract and sialic acid in a mass ratio of 1:(0.7-15):(0.5-10), preferably in a mass ratio of 1:(0.7-14.7):(0.5-10).

[0009] This invention reveals that existing research largely focuses on the efficacy of single components in improving age-related cognitive impairment, and their effectiveness and safety still require further improvement. To explore safe and effective nutritional intervention strategies, this invention, through extensive research, found that when *Lactobacillus plantarum* HEAL9, oat extract, and sialic acid are combined in a specific ratio in a zebrafish model of age-related cognitive impairment induced by D-galactose combined with sleep deprivation, compared to a single component, it significantly increases the proportion of movement in the blue area of ​​the cross maze, increases telomerase activity, and decreases β-galactosidase staining intensity, indicating that it can effectively improve age-related cognitive impairment.

[0010] If other cognitively supportive components (such as theanine, nervonic acid, or phosphatidylserine) known in the art are used instead of the composition of this invention, the desired results may not be obtained.

[0011] In this invention, oat extract and sialic acid are food ingredients, and *Lactobacillus plantarum* HEAL9 is a clinically proven safe probiotic. Therefore, the composition of this invention also has the characteristics of being natural and safe.

[0012] Preferably, in the application of the present invention, the composition comprises *Lactobacillus plantarum* HEAL9, oat extract, and sialic acid in a mass ratio of 1:(7-15):(0.5-1); more preferably, the composition comprises *Lactobacillus plantarum* HEAL9, oat extract, and sialic acid in a mass ratio of 1:(7-14.7):(0.5-1); or preferably, the composition comprises *Lactobacillus plantarum* HEAL9, oat extract, and sialic acid in a mass ratio of 1:(0.7-2.1):(8-10).

[0013] In one specific embodiment of the present invention, the composition comprises *Lactobacillus plantarum* HEAL9, oat extract, and sialic acid in a mass ratio of 1:14.7:0.5, 1:0.7:10, 1:7:1, 1:0.7:8, or 1:2.1:10.

[0014] Preferably, the composition comprises *Lactobacillus plantarum* HEAL9, oat extract, and sialic acid in a mass ratio of 1:14.7:0.5 or 1:0.7:10.

[0015] When the preferred composition ratio of the substances in this invention is used, even better results can be obtained. Overall, a mass ratio of 1:0.7:10 is optimal for improving age-related cognitive impairment.

[0016] The present invention also provides a composition as described above.

[0017] The composition of the present invention showed superior effects compared to any single component in the composition in the detection of behavioral indicators (blue percentage) and two aging-related biochemical indicators (telomerase activity and β-galactosidase staining), indicating that the composition of the present invention can achieve synergistic effects in improving cognitive function, enhancing anti-aging ability and inhibiting aging, thereby achieving overall improvement in aging-related cognitive impairment.

[0018] The present invention also provides a method for preparing the above composition, which includes the step of mixing Lactobacillus plantarum HEAL9, oat extract and sialic acid.

[0019] Those skilled in the art can use methods known in the art to mix the substances in the above composition, and the present invention does not impose any special limitations on this.

[0020] The present invention also provides a pharmaceutical product comprising the above-described composition.

[0021] The drug can be used to improve age-related cognitive impairment.

[0022] Preferably, the medicine further includes pharmaceutically acceptable excipients.

[0023] The pharmaceutical products of the present invention may include pharmaceutically acceptable excipients known in the art; the dosage form may be tablets, capsules, granules, powders, pills, oral solutions, syrups, emulsions, suspensions, drop pills, enteric-coated preparations, and other pharmaceutical dosage forms known in the art.

[0024] The active ingredient in the pharmaceutical product of the present invention may be only the composition described above, or may also include other active ingredients with the same or different functions.

[0025] The beneficial effects of this invention are at least as follows:

[0026] This invention utilizes a specific ratio of *Lactobacillus plantarum* HEAL9, oat extract, and sialic acid to significantly improve age-related cognitive impairment, providing a new and effective method for improving the brain health and quality of life of the relevant middle-aged and elderly populations. Detailed Implementation

[0027] To make the objectives, technical solutions, and advantages of this invention clearer, the technical solutions of this invention will be clearly and completely described below in conjunction with the embodiments of this invention. Obviously, the described embodiments are only some embodiments of this invention, not all embodiments. Based on the embodiments of this invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of this invention.

[0028] Unless otherwise specified, the experimental methods used in the following examples are conventional methods. Unless otherwise specified, the materials and reagents used in the following examples are commercially available or prepared according to conventional methods in the art.

[0029] In this invention, *Lactobacillus plantarum* HEAL9 (hereinafter referred to as "HEAL9") was purchased from Probi®, traded under the name Sensia, with a viable count of 6 × 10⁻⁶. 11 cfu / g. The oat green extract described in the specific embodiments section of this invention was purchased from IFF HealthSciences, under the trade name Neuravena® Oat Green Extract (trade name in China: Oat Green Extract Solid Beverage), wherein the content of the active ingredient oat green extract is 70%. Sialic acid was purchased from JABYTE Biotechnology (Wuhan) Co., Ltd., under the trade name N-acetylneuraminic acid.

[0030] Nervonic acid was purchased from Heze Zhonghe Jianyuan Biotechnology Co., Ltd. It is cis-15-tetracosenoic acid produced from rapeseed oil through saponification, acidification, extraction, separation, crystallization, and drying processes. Phosphatidylserine (PS) was purchased from Beijing Yifan International Trade Co., Ltd., produced by IFF, and marketed under the trade name Sharp PS®60P-FP CNPCN. It is a powdered phosphatidylserine product, with soybean lecithin as its main raw material and a PS content of 60%. Theanine was purchased from Huisong Pharmaceutical, marketed under the trade name Tea Theanine. It is a yellow-brown amorphous powder extracted from tea leaves.

[0031] Example 1

[0032] This embodiment provides a composition comprising *Lactobacillus plantarum* HEAL9, oat extract, and sialic acid, wherein the mass ratio of *Lactobacillus plantarum* HEAL9, oat extract, and sialic acid is 1:21:0.5.

[0033] Example 2

[0034] This embodiment provides a composition comprising *Lactobacillus plantarum* HEAL9, oat extract, and sialic acid, wherein the mass ratio of *Lactobacillus plantarum* HEAL9, oat extract, and sialic acid is 1:1:10.

[0035] Example 3

[0036] This embodiment provides a composition comprising *Lactobacillus plantarum* HEAL9, oat extract, and sialic acid, wherein the mass ratio of *Lactobacillus plantarum* HEAL9, oat extract, and sialic acid is 1:10:1.

[0037] Example 4

[0038] This embodiment provides a composition comprising *Lactobacillus plantarum* HEAL9, oat extract, and sialic acid, wherein the mass ratio of *Lactobacillus plantarum* HEAL9, oat extract, and sialic acid is 1:1:8.

[0039] Example 5

[0040] This embodiment provides a composition comprising *Lactobacillus plantarum* HEAL9, oat extract, and sialic acid, wherein the mass ratio of *Lactobacillus plantarum* HEAL9, oat extract, and sialic acid is 1:3:10.

[0041] Comparative Example 1

[0042] This comparative example provides a composition comprising *Lactobacillus plantarum* HEAL9, oat extract, and sialic acid, wherein the mass ratio of *Lactobacillus plantarum* HEAL9, oat extract, and sialic acid is 98:1:1.

[0043] Comparative Example 2

[0044] This comparative example provides a composition comprising *Lactobacillus plantarum* HEAL9, oat extract, and sialic acid, wherein the mass ratio of *Lactobacillus plantarum* HEAL9, oat extract, and sialic acid is 10:1:1.

[0045] Comparative Example 3

[0046] This comparative example provides a composition comprising *Lactobacillus plantarum* HEAL9, oat extract, and sialic acid, wherein the mass ratio of *Lactobacillus plantarum* HEAL9, oat extract, and sialic acid is 1:1:98.

[0047] Comparative Example 4

[0048] This comparative example provides a composition comprising *Lactobacillus plantarum* HEAL9, oat extract, and sialic acid, wherein the mass ratio of *Lactobacillus plantarum* HEAL9, oat extract, and sialic acid is 1:98:1.

[0049] Comparative Example 5

[0050] This comparative example provides a composition comprising *Lactobacillus plantarum* HEAL9, oat extract, and nervonic acid, wherein the mass ratio of *Lactobacillus plantarum* HEAL9, oat extract, and nervonic acid is 1:1:10.

[0051] Comparative Example 6

[0052] This comparative example provides a composition comprising PS, oat extract and sialic acid, wherein the mass ratio of PS, oat extract and sialic acid is 1:1:10.

[0053] Comparative Example 7

[0054] This comparative example provides a composition comprising *Lactobacillus plantarum* HEAL9, theanine, and sialic acid, wherein the mass ratio of *Lactobacillus plantarum* HEAL9, theanine, and sialic acid is 1:1:10.

[0055] Experimental Example 1

[0056] This experimental example demonstrates the effects of the compositions from the above embodiments and comparative examples on improving aging and associated cognitive impairment. Specifically, the blue area motion percentage method in a cross-maze was used.

[0057] In behavioral tests, zebrafish exhibit an innate color preference, clearly favoring the blue arms in a colored cross maze, with the order of time spent on the blue arm being blue > red > green > yellow. Therefore, using the "percentage of movement in the blue area" as a cognitive indicator, with higher values ​​indicating better memory performance, is a commonly used behavioral indicator for assessing cognitive improvement.

[0058] At higher doses, D-galactose (D-gal) is metabolized by galactose oxidase into aldose and hydrogen peroxide, producing reactive oxygen species such as superoxide anions and inducing lipid peroxidation. This damages the cellular defense system and central nervous system, leading to aging characteristics such as cognitive impairment and oxidative stress. Sleep deprivation, as another stressor, causes decreased attention, reduced reaction time, and significantly impaired learning and memory performance in zebrafish. This experiment, using a combination of oxidative and physical stimulation, indirectly accelerates the aging process.

[0059] Experimental methods:

[0060] An experiment was conducted using a zebrafish aging and cognitive impairment model induced by D-galactose combined with sleep deprivation.

[0061] Wild-type AB strain zebrafish were randomly selected 3 days after fertilization (3 dpf) and placed in beakers, with 30 zebrafish treated in each beaker (experimental group). The following groups were established: normal control group ①, model control group ①, groups treated with *Lactobacillus plantarum* HEAL9 alone, oat extract, or sialic acid alone, as well as Examples 1-3 and Comparative Examples 1-4.

[0062] Except for the normal control group and the model control group, each group was given samples in water solution. The groups that were given Lactobacillus plantarum HEAL9, oat extract or sialic acid alone, as well as the example groups and comparative groups, were given samples at a total concentration of 30 μg / mL, with each beaker having a capacity of 20 mL.

[0063] Except for the normal control group, all other experimental groups were given D-galactose 12.8 mg / mL in water combined with physical stimulation (water rotation at 1500 rpm) to induce a zebrafish aging-related cognitive impairment model. After treatment at 28℃ for 2 days, zebrafish were randomly selected from each experimental group and placed in a cross maze. The maze was divided into four areas: yellow, blue, red, and green. Six mazes were placed in each group, with five zebrafish in each maze. Data were collected using a behavior analyzer, and the percentage (%) of the total distance the zebrafish moved in the blue area within 10 minutes relative to the total distance moved in the entire area was analyzed. This yielded six parallel experimental data points for each group (each data point was the sum of the test results of five fish in a single maze). The statistical analysis results of this index were used to evaluate the efficacy of the sample in improving aging-related cognitive impairment (cross maze). Statistical results are expressed as mean ± SE. Statistical analysis was performed using SPSS software, and p < 0.05 indicated statistical significance. The experimental results are shown in Table 1.

[0064] The improvement rate is calculated as follows: % = 100% × (mean of experimental group - mean of model group) / mean of model group.

[0065] Table 1

[0066]

[0067] In the table (if any), compare with the model control group ①, p<0.05, p<0.01, p<0.001;

[0068] Compared with the HEAL9 group, #p<0.05, ##p<0.01;

[0069] Compared with the oat green extract group, p<0.05, p<0.01, p<0.001;

[0070] Compared with the sialic acid group, %p<0.05, %%p<0.01.

[0071] This experiment further validated the effects of Examples 4-5 and Comparative Examples 5-7 on improving aging and associated cognitive impairment using the method described above (proportion of movement in the blue area of ​​the cross maze). Specifically, a normal control group ②, a model control group ②, and groups for Examples 4-5 and Comparative Examples 5-7 were set up. The experimental results are shown in Table 2.

[0072] Table 2

[0073]

[0074] In the table (if applicable), compare with the model control group ②. p<0.05, p<0.01, p<0.001;

[0075] Compared with the HEAL9 & oat extract & nervonic acid group, ^p<0.05, ^^p<0.01;

[0076] Compared with the HEAL9, theanine, and sialic acid group, ep < 0.05 and eep < 0.01;

[0077] Compared with the PS & oat extract & sialic acid group, ap<0.05, aap<0.01.

[0078] Based on the experimental results of each experimental subject in the two batches of experiments, the changes in the blue proportion (%) of the six parallel experimental data points (each experimental data point is the sum of the blue area movement proportions of the five fish in a single module) in each experimental group in each batch of experiments were statistically analyzed relative to the mean blue proportion (%) of the model control group. This change was denoted as Δblue proportion (Δblue proportion_i = blue proportion of the i-th experimental data point in the experimental group - mean blue proportion of the model control group, i = 1 to 6, representing the number of the parallel experimental data points in the same experimental group). Then, the data of the six Δblue proportions in the same experimental group were analyzed, and the results are shown in Table 3.

[0079] As shown in Table 3, after processing with the above-mentioned Δblue percentage, the Δblue percentage results (22.99% and 22.82%) obtained by the normal control group ① and normal control group ② in the two batches of experiments are very close. This indicates that the method of calculating the change value with the respective model control group as the baseline can effectively eliminate the differences between different experimental batches and make the results of the two batches of experiments comparable.

[0080] Table 3

[0081]

[0082] In the table (if available), compared with the HEAL9 group, #p<0.05, ##p<0.01;

[0083] Compared with the oat green extract group, p<0.05, p<0.01, p<0.001;

[0084] Compared with the sialic acid group, %p<0.05, %%p<0.01;

[0085] Compared with the HEAL9 & oat extract & nervonic acid group, ^p<0.05, ^^p<0.01;

[0086] Compared with the HEAL9 & theanine & sialic acid group, ep<0.05, eep<0.01, eeep<0.001;

[0087] Compared with the PS & oat extract & sialic acid group, ap<0.05, aap<0.01, aaap<0.001.

[0088] Experimental Example 2

[0089] Telomerase replenishes nucleotides at the ends of mitochondria after cell division and, under oxidative stress, transports its catalytic subunit TERT to mitochondria, enhancing antioxidant capacity. Insufficient telomerase function can lead to rapid telomere shortening and premature aging phenotypes. Measuring telomerase activity can reflect the potential of a formulation to delay aging.

[0090] Experimental methods: Wild-type AB strain zebrafish with a 3 dpf growth rate were randomly selected and placed in beakers. Each beaker (experimental group) contained 30 zebrafish. Groups were set up including a normal control group, a model control group, a positive control group, groups treated with *Lactobacillus plantarum* HEAL9 alone, oat extract, or sialic acid alone, as well as Examples 1-3 and Comparative Examples 1-4.

[0091] Except for the normal control group and the model control group, each group was given samples in water solution. The groups that were given Bacillus plantarum HEAL9, oat extract or sialic acid alone, as well as the example groups and comparative groups, were given samples at a total concentration of 30 μg / mL. The positive control was ginseng stem and leaf total saponin tablets, with an application concentration of 100 μg / mL. Each beaker had a capacity of 50 mL.

[0092] Except for the normal control group, all other experimental groups were given D-(+)-galactose 12.8 mg / mL in aqueous solution combined with physical stimulation (water rotation at 1500 rpm) to induce a zebrafish aging-associated cognitive impairment model. Three parallel experiments were conducted. After treatment at 28℃ for 2 days, the zebrafish from each group were cryopreserved in liquid nitrogen. Telomerase activity was detected using the Zebra Fish TE ELISA KIT kit (batch number H25Y08, ​​Shanghai Hengyuan Biotechnology Co., Ltd., China). Statistical analysis of this indicator was used to evaluate the efficacy of the samples in improving aging-associated cognitive impairment (telomerase activity). Statistical results are expressed as mean ± SE. Statistical analysis was performed using SPSS software; p < 0.05 indicated statistical significance.

[0093] The results are shown in Table 4.

[0094] Table 4

[0095]

[0096] In the table (if applicable), compare with the model control group. p<0.05, p<0.01, p<0.001;

[0097] Compared with the HEAL9 group, #p<0.05, ##p<0.01, ###p<0.001;

[0098] Compared with the oat green extract group, p<0.05, p<0.01, p<0.001;

[0099] Compared with the sialic acid group, %p<0.05, %%p<0.01, and %%%p<0.001.

[0100] The telomerase activity test results of Comparative Example 2 were comparable to those of Example 1, but relying solely on telomerase activity as a single indicator could not prove that Comparative Example 2 had the effect of improving aging and associated cognitive impairment.

[0101] Experimental Example 3

[0102] High activity of β-galactosidase (SA-β-gal) at pH 6.0 is a key characteristic of senescent cells and a widely used biomarker of cellular senescence. SA-β-gal is a hydrolytic enzyme within lysosomes, and senescent cells are typically accompanied by an increase in the number and volume of lysosomes. SA-β-gal is believed to be primarily located in lysosomes, and lysosomal amplification directly leads to increased enzyme activity. The cellular senescence β-galactosidase staining kit uses X-gal as a substrate. In senescent cells, β-galactosidase catalyzes the production of a deep blue product; the deeper the color, the more β-galactosidase-positive cells (senescent cells) there are, and the more severe the senescence. In zebrafish exhibiting senescence accompanied by cognitive impairment, the average intensity of β-galactosidase staining increases.

[0103] Experimental methods: Wild-type AB strain zebrafish with a 3 dpf growth rate were randomly selected and placed in beakers. Each beaker (experimental group) contained 30 zebrafish. Groups were set up including a normal control group, a model control group, a positive control group, groups treated with *Lactobacillus plantarum* HEAL9 alone, oat extract, or sialic acid alone, as well as Examples 1-3 and Comparative Examples 1-4.

[0104] Except for the normal control group and the model control group, each group was given samples in water. Groups treated with *Lactobacillus plantarum* HEAL9, oat extract, or sialic acid alone, as well as the example groups and comparative groups, were given samples at a total concentration of 30 μg / mL. The positive control was ginseng stem and leaf total saponins tablets at a concentration of 100 μg / mL. Each beaker had a capacity of 50 mL. Except for the normal control group, all other experimental groups were given a zebrafish aging and cognitive impairment model induced by a combination of D-(+)-galactose 12.8 mg / mL in water and physical stimulation (water rotation at 1500 rpm). After treatment at 28℃ for 2 days, zebrafish from each experimental group were stained using a cellular senescence β-galactosidase staining kit (batch number 031924240704, Shanghai Beyotime Biotechnology Co., Ltd., China). After staining, 10 zebrafish from each experimental group were randomly selected and photographed under a dissecting microscope. Data were collected using NIS-Elements D 3.20 advanced image processing software, and the average β-galactosidase staining intensity in zebrafish was analyzed. The statistical analysis results of this index were used to evaluate the efficacy of the samples in improving aging-related cognitive impairment (β-galactosidase staining). Statistical results are expressed as mean ± SE. Statistical analysis was performed using SPSS software, and p < 0.05 indicated statistical significance. The results are shown in Table 5.

[0105] Table 5

[0106]

[0107] In the table (if applicable), compare with the model control group. p<0.05, p<0.01, p<0.001;

[0108] Compared with the HEAL9 group, #p<0.05;

[0109] Compared with the oat green extract group, p<0.05, p<0.001;

[0110] Compared with the sialic acid group, %p<0.05, %%p<0.01.

[0111] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them; 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; and these 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. The use of a composition in the preparation of a product for improving age-related cognitive impairment, characterized in that, The composition comprises *Lactobacillus plantarum* HEAL9, oat extract, and sialic acid in a mass ratio of 1:(0.7-15):(0.5-10); the oat extract is made from the stems and leaves of the immature oat plant, through extraction with 30% ethanol, concentration, drying, and grinding.

2. The application according to claim 1, characterized in that, The composition comprises *Lactobacillus plantarum* HEAL9, oat extract, and sialic acid in a mass ratio of 1:(7-15):(0.5-1).

3. The application according to claim 1, characterized in that, The composition comprises *Lactobacillus plantarum* HEAL9, oat extract, and sialic acid in a mass ratio of 1:(0.7-2.1):(8-10).

4. The application according to claim 1, characterized in that, The composition comprises *Lactobacillus plantarum* HEAL9, oat extract, and sialic acid in a mass ratio of 1:14.7:0.5, 1:0.7:10, 1:7:1, 1:0.7:8, or 1:2.1:

10.

5. The application according to claim 4, characterized in that, The composition comprises *Lactobacillus plantarum* HEAL9, oat extract, and sialic acid in a mass ratio of 1:14.7:0.5 or 1:0.7:

10.

6. A composition, characterized in that, As described in any one of claims 1-5.

7. A method for preparing the composition of claim 6, characterized in that, This includes the step of mixing Lactobacillus plantarum HEAL9, oat extract, and sialic acid.

8. A medicine, characterized in that, Includes the composition of claim 6.

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