Composition for preventing or improving focal adjustment function decline

Abstract

To provide a composition for preventing and / or improving deterioration of focal point adjusting function caused by asthenopia.SOLUTION: A composition for preventing and / or improving focal adjustment hypofunction due to asthenopia, comprising lactic acid bacteria WB2000, trans-resveratrol, and a crocetin-containing gardenia extract.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] The present invention relates to a composition for preventing and / or ameliorating impaired accommodative function. [Background technology]

[0002] In recent years, with the rapid development of IT, computers and smartphones have become necessities not only in the workplace but also in school education and private life, and their daily use is becoming commonplace. According to the Ministry of Internal Affairs and Communications' "Survey on Telecommunications Usage Trends," the internet usage rate (individuals) in Japan reached 89.4% in 2019, and is expected to remain stable at 83-85% until 2022. The types of internet usage devices (individuals) with the highest percentages are smartphones at 71.2%, followed by PCs at 48.5%, followed by televisions, tablet devices, and home game consoles.

[0003] VDT stands for Visual Display Terminals. Specifically, it refers to a computer output device (e.g., a computer screen or other image display device) consisting of a display and keyboard, which displays text, figures, graphics, and video. VDT work involves tasks such as data entry, search, and collation, the creation, editing, and modification of text and images, programming, and monitoring. Survey results indicate that approximately 80% of VDT workers who use computers in the workplace report symptoms of physical fatigue. These symptoms include: (a) eye symptoms (eye strain, dry eyes, etc.); (b) musculoskeletal symptoms (stiffness, lower back pain, cervicobrachial syndrome, carpal tunnel syndrome, etc.); and (c) mental symptoms (irritability, insomnia, etc.). To address health problems caused by long, continuous work hours and unfavorable work environments (workspace, machine layout, etc.), the Ministry of Health, Labor, and Welfare established the "Guidelines for Occupational Health Management of VDT Workers" (Notification No. 0405001, dated April 5, 2002). The above guidelines also stipulate health management for VDT workers.

[0004] With internet penetration rates exceeding half of countries worldwide, it is said that approximately 50% to 90% of VDT users show signs of digital eye strain. According to the American Optometric Association, the most common symptoms associated with digital eye strain are eye strain, headache, blurred vision, dry eyes, and neck and shoulder pain. The mechanisms of digital eye strain can be broadly divided into internal mechanisms caused by accommodation and external mechanisms caused by dry eyes. Headache, blurred vision, and neck and shoulder pain are symptoms caused by accommodation, while symptoms such as burning sensation, dryness, fatigue, light sensitivity, and discomfort are symptoms caused by dry eyes. It has been reported that eye strain accounts for the highest proportion of physical symptoms (VDT syndrome) among VDT workers in Japan. Even younger generations with sufficient accommodative power are experiencing IT ophthalmopathy, technostress ophthalmopathy, or eye strain due to the use of digital devices. It has also been suggested that uncorrected or undercorrected presbyopia may worsen eye strain in middle-aged and older people. Furthermore, lifestyle changes due to the COVID-19 global pandemic have been suggested to be accelerating the onset of presbyopia, and the number of patients suffering from eye strain due to the use of digital devices is predicted to increase in the future.

[0005] As part of maintaining and improving health, it can be taken in moderate amounts from health foods, functional foods, foods with nutrient claims or foods for specified health uses to supplement ingredients that are lacking in the daily diet or that are attracting attention. In functional food products, bilberry-derived anthocyanins have been reported to regulate eye condition by alleviating eye fatigue, dryness, and decreased focus adjustment, while astaxanthin has been reported to reduce strain on the shoulders and lower back caused by eye use.

[0006] Crocetin, a type of carotenoid, has been reported to improve blood flow to the eyes, brain, and lungs and to suppress cancer inflammation, and has been suggested to relieve ciliary muscle tension associated with VDT work (Non-patent document 1). Resveratrol has been reported to have an effect on cardiovascular disease and to extend lifespan. It has also been reported to maintain memory, which is part of cognitive function that declines with age in middle-aged and elderly people, and to play an important role in age-related eye diseases (Non-patent document 2).

[0007] It has been reported that a composition containing one or more components selected from the group consisting of lutein, fish oil, lactoferrin, vitamins, aminobutyric acid, and zinc, and lactic acid bacteria (e.g., Enterococcus faecium WB2000, hereinafter also referred to as Lactobacillus WB2000), increases tear secretion and improves dry eye (Patent Document 1). The results of Nagashima et al.'s simultaneous administration of highly purified resveratrol and lactic acid bacteria WB2000 to rats suggested that the decrease in elasticity of the lens caused by aging was improved (Non-Patent Document 3). With the increase in VDT ​​users, it is hoped that appropriate intervention will be possible before symptoms of not only presbyopia in the elderly but also VDT syndrome and decreased focusing function due to eye strain appear in adults. [Prior art documents] [Non-patent literature]

[0008] [Non-Patent Document 1] Vision Science, Vol. 28, No. 2, pp. 77-84, 2007 [Non-patent document 2] The American Journal Of Pathology,Oct2024,Vol.177,Issue 4,1725-1731 [Non-patent document 3] Scientific Reports, (2021)11:2174, 2021 [Patent Document 1] WO2016 / 032000 Summary of the Invention [Problem to be solved by the invention]

[0009] As described above, crocetin, when taken alone, alleviates the decline in focusing ability caused by eye fatigue due to computer work, etc., and has the function of regulating eye condition. Simultaneous administration of lactic acid bacteria and resveratrol improves the decline in lens elasticity caused by aging. However, it is expected that the function of lactic acid bacteria can be enhanced by taking other ingredients at the same time as lactic acid bacteria. Methods of combining lactic acid bacteria with other ingredients have not been fully studied. Furthermore, the effect of lactic acid bacteria in alleviating or improving the decline in focusing ability has not been fully studied. The problem to be solved by the present invention is to provide a composition for preventing and / or improving symptoms of impaired focusing function, such as impaired focusing function due to VDT syndrome, IT ophthalmopathy, presbyopia and / or eye strain. [Means for solving the problem]

[0010] In a randomized, placebo-controlled, double-blind crossover study, the inventors administered the compound orally and evaluated objective focusing function and subjective symptoms using a diary questionnaire. As a result, they found that the compound has an excellent effect of improving decreased focusing function and also has the effect of improving eye fatigue and redness of the eyes. That is, the present invention provides the following composition. The present inventors have discovered that a composition containing the lactic acid bacterium Enterococcus faecium WB2000, trans-resveratrol, and a gardenia extract containing crocetin prevents and / or improves impaired accommodative function, and have completed the present invention.

[0011] That is, the present invention relates to a composition for preventing and / or improving impaired focusing function due to eye strain, which comprises lactic acid bacteria as well as resveratrol and crocetin. [1] An oral composition for preventing or improving impaired focusing ability, comprising at least one component selected from the group consisting of resveratrol and crocetin, and the lactic acid bacterium Enterococcus faecium. [2] An oral pharmaceutical composition for preventing or improving impaired focusing function, comprising at least one component selected from the group consisting of resveratrol and crocetin, and the lactic acid bacterium Enterococcus faecium. [3] A food composition for preventing or improving impaired focusing ability, comprising at least one component selected from the group consisting of resveratrol and crocetin, and the lactic acid bacterium Enterococcus faecium. [4] An oral composition for preventing or improving decreased focusing function due to VDT syndrome, presbyopia, or eye strain, comprising at least one component selected from the group consisting of resveratrol and crocetin, and the lactic acid bacterium Enterococcus faecium. [5] An oral composition for improving eye fatigue or eye redness, comprising at least one component selected from the group consisting of resveratrol and crocetin, and lactic acid bacteria Enterococcus faecium. [Effects of the Invention]

[0012] The composition of the present invention for preventing or improving impaired focusing ability makes it possible to effectively prevent or improve impaired focusing ability due to presbyopia, VDT syndrome or eye strain. [Brief explanation of the drawings]

[0013] [Figure 1] Time schedule for each period (screening 2, week 0, week 4) [Figure 2] Flow from subject enrollment to analysis [Figure 3] Change in HFC-1 before and after rest (dominant eye) [Figure 4] Diary questionnaire items with significant differences DETAILED DESCRIPTION OF THE INVENTION

[0014] The present invention relates to a composition comprising lactic acid bacteria and resveratrol and crocetin. As for the lactic acid bacteria Enterococcus faecium, if the effects of the present invention can be obtained, There are no particular limitations, but a specific example is Enterococcus Faecium WB2000 (International Deposit No. NITE BP-1913).

[0015] Lactic acid bacteria WB2000 can be publicly used in the form of, for example, live cells, wet cells, dried cells, killed cells, culture supernatant, culture containing medium components, freeze-dried cells or their multiplication products.

[0016] Resveratrol is a white natural substance belonging to the polyphenol stilbenoid group, and is preferably contained in grape skin, grape buds, grape stems, peanut skins, and red wine. There are no particular limitations on the resveratrol as long as it can provide the effects of the present invention, but examples include trans-resveratrol, cis-resveratrol, resveratrol glycoside, and resveratrol dimer, with trans-resveratrol being preferred.

[0017] There are no particular limitations on the crocetin used as long as it achieves the effects of the present invention, but pharmaceutically acceptable salts of crocetin, crocetin-containing gardenia extracts, gardenia pigments, and saffron extracts are more preferred, with crocetin-containing gardenia extracts and pharmaceutically acceptable salts of crocetin being even more preferred.

[0018] The content of the lactic acid bacteria Enterococcus faecium may be any amount, but is typically 0.001 to 90% by weight, preferably 0.001 to 20% by mass, and more preferably 0.01 to 10% by mass. The content of the lactic acid bacteria Enterococcus faecium per daily dose or intake of the composition of the present invention is preferably 1 million to 100 billion lactic acid bacteria, more preferably 10 million to 100 billion lactic acid bacteria, and even more preferably 100 million to 100 billion lactic acid bacteria.

[0019] The composition is not particularly limited as long as it is ingestible by humans or animals, and may be, for example, a pharmaceutical composition or a food composition.

[0020] Examples of dosage forms of the composition include soft capsules, capsules, powders, fine granules, granules, tablets, lozenges, syrups, jellies, liquids, etc. These dosage forms allow the composition to be safely administered or ingested.

[0021] The composition may contain additives such as excipients, binders, disintegrants, coating agents, lubricants, dispersants, stabilizers, etc. Adding additives that can be commonly used in the technical field of manufacturing pharmaceutical compositions or food compositions, It can be produced according to the following.

[0022] Examples of excipients include sugars such as sucrose, lactose, mannitol, and glucose; and starches such as corn starch, potato starch, rice starch, and partially pregelatinized starch.

[0023] Examples of binders include polysaccharides such as chitosan, dextrin, sodium alginate, carrageenan, guar gum, gum arabic, and agar; natural polymers such as tragacanth, gelatin, and gluten; cellulose derivatives such as hydroxypropyl cellulose, methyl cellulose, hydroxypropyl methyl cellulose, ethyl cellulose, hydroxypropyl ethyl cellulose, and sodium carboxymethyl cellulose; and synthetic polymers such as polyvinylpyrrolidone, polyvinyl alcohol, polyvinyl acetate, polyethylene glycol, polyacrylic acid, polymethacrylic acid, and vinyl acetate resin.

[0024] Examples of disintegrants include cellulose derivatives such as carboxymethyl cellulose, carboxymethyl cellulose calcium, and low-substituted hydroxypropyl cellulose; and starches such as carboxymethyl starch sodium, hydroxypropyl starch, corn starch, potato starch, rice starch, and partially pregelatinized starch.

[0025] Examples of coating agents include water-insoluble polymers such as dimethylaminoethyl methacrylate-methacrylic acid copolymer, polyvinyl acetal diethylaminoacetate, ethyl acrylate-methacrylic acid copolymer, ethyl acrylate-methyl methacrylate-trimethylammonium ethyl methacrylate chloride copolymer, and ethyl cellulose; enteric polymers such as methacrylic acid-ethyl acrylate copolymer, hydroxypropyl methylcellulose phthalate, and hydroxypropyl methylcellulose acetate succinate; and water-soluble polymers such as methylcellulose, hydroxypropyl methylcellulose, polyvinylpyrrolidone, and polyethylene glycol.

[0026] Examples of lubricants include talc, stearic acid, calcium stearate, magnesium stearate, colloidal silica, hydrous silicon dioxide, waxes, and hardened oils.

[0027] Examples of dispersants include emulsifiers such as lecithin, glycerin fatty acid esters, and polyglycerin fatty acid esters, and thickening polysaccharides such as guar gum.

[0028] Examples of stabilizers include beeswax, glycerin fatty acid esters, and hardened oils.

[0029] The composition may be administered in a single dose or in several divided doses as required.

[0030] When the composition of the present invention is used as a food composition, it may be added to food in advance or at the time of ingestion. Examples of foods include yogurt, jelly, and modified milk. It may also be ingested alone as a nutritional supplement or a food with functional claims.

[0031] The composition of the present invention contains the lactic acid bacteria Enterococcus faecium and one or more components selected from the group consisting of resveratrol and crocetin, thereby enhancing the function of the lactic acid bacteria. The functions of the composition of the present invention include preventing or improving a decline in focus accommodation function, preventing or improving a decline in focus accommodation function due to VDT syndrome, presbyopia, or eye strain, alleviating eye strain, improving eye redness or eye fatigue, and reducing stress caused by VDT use.

[0032] Decreased focusing ability can be caused by VDT syndrome, IT ophthalmopathy, presbyopia, eye strain, or prolonged use of VDTs. Eye strain and a lifestyle that overuses the eyes can lead to a decrease in blinking, leading to symptoms of focusing (headaches, blurred vision, neck and shoulder pain) and dry eye symptoms (dry eyes, burning sensation, sensitivity to light, and discomfort). Oral administration or ingestion of the composition of the present invention can prevent or improve the decline in focusing ability and relieve or alleviate redness and eye fatigue. Conventionally, methods used to treat VDT syndrome or IT ophthalmopathy and to relieve eye strain include administering vitamins or synthetic compounds as eye drops, and ensuring an appropriate working environment and comfortable posture for VDT use. The composition of the present invention can prevent or improve a decline in focusing function by oral administration or ingestion, and can reduce the burden on patients when administered. [Example]

[0033] The present invention will be explained in more detail below with reference to examples, but the present invention is not limited to these examples.

[0034] (Example 1) Composition containing lactic acid bacteria Enterococcus faecium TIFF2026020077000002.tif3366 (Comparative Example 1) TIFF2026020077000003.tif3765

[0035] (Test example) Improvement study of impaired focus accommodation I. Subjects and Methods 1. Subjects 1) Recruitment of subjects Eligible subjects were those who met the inclusion criteria below, voluntarily wished to participate in the study, and provided written consent. 2) Inclusion and Exclusion Criteria Japanese men and women who met the inclusion criteria and did not meet the exclusion criteria were enrolled in the screening test. The inclusion criteria were the following nine items: <1> Age: 25 years old or older, under 40 years old, <2> Gender: Japanese men and women, <3> Healthy individuals who have subjective symptoms of eye strain (meaning "eye fatigue") and who the investigator has determined to be suitable for participation in this study. <4> Those who work VDT for an average of 4 hours or more per day per week, <5> (Neither naked nor corrected) eyesight 0.7 or higher, <6> Those who do not have any eye diseases other than refractive errors (nearsightedness, farsightedness, astigmatism), <7> Those who do not regularly use blue-blocking glasses or screens, <8> Those who can enter electronic journal entries using a smartphone or PC, <9> Those who have received a thorough explanation of the purpose and content of the study, fully understood it, volunteered to participate, and provided written consent to participate in the study. The following 18 exclusion criteria apply:[1] Subjects currently receiving outpatient treatment for any illness or receiving medication or herbal medicine, [2] Subjects who have previously undergone LASIK surgery, [3] Subjects undergoing dietary therapy or exercise therapy under the supervision of a doctor, [4] Subjects with a current or past history of serious illness or organic eye disease, [5] Subjects with entropion or trichiasis, [6] Subjects with measured astigmatism of 1.25D or more, [7] Subjects wearing eyelash extensions, [8] Subjects who are not getting enough sleep, [9] Subjects at risk of developing allergic conjunctivitis (seasonal or perennial) during the study period,

[10] Subjects currently using over-the-counter medicines and quasi-drugs (including eye drops), specified health foods, functional foods, health foods, or supplements, and

[11] Subjects who regularly consume yogurt or lactic acid bacteria drinks for health promotion purposes. (However, those who are able to stop taking the drug during the study period after consent is obtained are eligible),

[12] those with current or past drug or food allergies,

[13] those who drink a lot of alcohol (equivalent to 60g or more of alcohol per day),

[14] those who smoke,

[15] those who have difficulty maintaining a certain lifestyle during the study period, such as those planning to make major changes to their lifestyle (e.g., diet, sleep, exercise), working night shifts or other shift work, or planning to travel abroad,

[16] those who are pregnant, breastfeeding, or wish to become pregnant during the study period,

[17] those who have participated in or are currently participating in other clinical trials within one month prior to consent, or those who plan to participate during the study period, and

[18] those who the principal investigator deems unsuitable to participate in this study.

[0036] A person in charge of the test food, who was not directly involved in the study, randomly divided the subjects into two groups, one that took the test food first, and one that took the placebo first, using gender, age, BMI, and changes in HFC1 in the dominant and non-dominant eyes (from before VDT load to after VDT load (Figure 1, between A and B), from before VDT load to after rest after VDT load (Figure 1, between A and C), and from after VDT load to after rest after VDT load (Figure 1, between B and C)) as stratification factors. As this study was evaluated in the dominant eye, the dominant eye was determined using the hole-in-card method at the time of screening prior to the study. 3) Setting the number of cases The target number of cases at the start of this study was 30.

[0037] 2. Ingredients of the test food The test food was Example 1. The placebo food was Comparative Example 1. The placebo food did not contain any functional ingredients and was designed with food coloring so that subjects could not distinguish between the two foods. The test food was provided by Wakamoto Pharmaceutical Co., Ltd. This was a double-blind study, and throughout the study period, subjects, the investigators, and staff at the medical institution involved in the study were unaware of the assigned group.

[0038] 3. Method and duration of test food intake Patients were asked to take two tablets once daily after breakfast for four weeks.

[0039] 4. Study Design This study was a randomized, placebo-controlled, double-blind, crossover study to verify the safety and effectiveness of the test food, a compound supplement, in suppressing the decline in focusing function caused by eye strain. 33 Japanese subjects who were eligible to participate in this study were asked to take either the test food or a placebo food for 4 weeks in each period. The test food was alternated between Periods I and II, with a 4-week washout period between Periods I and II. Subjects were evaluated when they visited the clinic. The study schedule is shown in Table 1, and the time schedule on the day of the examination is shown in Figure 1. Upon arrival at the clinic, subjects were weighed and interviewed, then rested with an eye mask on, and then completed a medical record questionnaire (Table 2, items <4> After measuring HFC in the right eye and then the left eye, the patient was subjected to a one-hour VDT load. The VDT load consisted of playing the handheld game "Tetris (registered trademark) (Tetris Holding, LLC)" with the patient's gaze held 45 cm away from the screen for one hour. After the HFC measurement, the patient completed a medical record questionnaire (Table 2, items <2> <3> ) and then had the patient rest for 20 minutes with an eye mask on. Finally, the HFC was measured in the right eye and then the left eye, and the patient was asked to fill out a medical record questionnaire (Table 2, items <4> ) and the survey was completed. The medical record questionnaire was administered at the second screening and at each visit. The diary questionnaire consisted of 12 items about subjective symptoms related to the eyes and the whole body for the three days before each visit, and the total score was calculated (Table 3). Patients were required to abstain from alcohol from the day before each test until the end of the test, and on the day of the blood test, they were required to finish eating at least six hours before the test and to abstain from eating and drinking anything other than water until the end of the test.

[0040] 5.Conflict of interest Wakamoto Pharmaceutical Co., Ltd. provided research support for the conduct of this study.

[0041] 6. Ethical Considerations This study complied with the "Declaration of Helsinki" (amended at the WMA General Assembly in Fortaleza, Brazil, October 2013) and the "Ethical Guidelines for Medical Research Involving Human Subjects (December 22, 2014 / partially revised February 28, 2017)." The ethical review committee of the Suda Clinic Institutional Review Board of the Hakusuikai Medical Corporation reviewed the ethical and appropriateness of the study plan and obtained approval (approval date: June 29, 2021) (UMIN registration number: UMIN000044917). All subsequent tests were performed at the National Sakura Hospital of the Kookai Medical Corporation. Subjects were fully informed of the study before participating, and written consent was obtained.

[0042] 7. Testing methods and evaluation items 1) Primary endpoint: Change in HFC The primary endpoint was the change in HFC-1. HFC is the average power spectrum obtained by frequency analysis of the waveform of the accommodative response obtained by moving the target from distance to near in 0.5D steps between +0.5 and -3.0D, based on the minimum refraction value. 19) The HFC-119) was the average HFC value obtained when the accommodative response was within -0.75D from the minimum refraction value. The HFC-1 value is the HFC value when little or no accommodative effort is being made and quantifies the basal ciliary muscle tone. HFC was measured using an autorefractometer, ARK-1s® (NIDEK), and accommodation function measurement software, AA-2® (NIDEK). The changes in HFC-1 in each eye were evaluated from before VDT stress to after VDT stress (Figure 1, change between A and B), from before VDT stress to after rest after VDT stress (Figure 1, change between A and C), and from after VDT stress to after rest after VDT stress (Figure 1, change between B and C: before and after rest).

[0043] 2) Secondary endpoints: Change in accommodative response, medical record questionnaire, diary questionnaire The accommodative response was the difference between the minimum and maximum refractive values, and was detected simultaneously with the HFC measurement using the AA-2 (registered trademark) accommodative function measurement software. The changes in the accommodative response of each eye were evaluated: the change from before VDT stress to after VDT stress (Figure 1, change between A and B), the change from before VDT stress to after VDT stress (Figure 1, change between A and C), and the change from after VDT stress to after VDT stress (Figure 1, change between B and C: before and after rest). The evaluation scores for each item in the medical record questionnaire, the evaluation scores for each item in the diary questionnaire, and the total value were evaluated.

[0044] 3) Safety evaluation items: blood tests, urine tests, physical examinations (weight, BMI, vital signs), incidence of side effects, other accompanying symptoms For safety evaluation, blood tests, urine tests, and physical examinations (weight, BMI, vital signs) were performed at the primary screening and at week 4 of each of periods I and II. Hematological test items included red blood cell count, white blood cell count, hemoglobin, hematocrit, platelet count, MCV, MCH, and MCHC, and blood biochemistry test items included total protein, triglycerides, total cholesterol, HDL-C, LDL-C, ALP, AST, ALT, γ-GTP, LDH, uric acid, urea nitrogen, total bilirubin, albumin, creatinine, CPK, FBS, HbA1c, CRP, Na, and K. A medical interview was conducted at each visit to confirm the occurrence of side effects and accompanying symptoms.

[0045] 8. Analysis method and subjects Statistical analysis for this study was performed by a CRO contracted by Wakamoto Pharmaceutical Co., Ltd., the sponsor of the study. The primary endpoint, change in HFC-1, and the secondary endpoints, adaptive response, medical record questionnaire scores, and diary questionnaire scores, were compared between groups before and after ingestion of the test food and placebo, as well as between groups for differences between week 0 and week 4 after ingestion of the test food and placebo. Analysis was performed using a linear mixed model with fixed effects of food intake, sequence, period, measurement point, and interaction between food intake and measurement point, covariate, and subject as a random effect. SPSS (Ver. 28) was used as the statistical software. A two-sided test with a significance level of 5% was used, and if a significant difference was observed, it was concluded that the null hypothesis was rejected. Carryover effects were determined based on the change in HFC-1, the primary endpoint, with a significance level of 10%. Of the 33 subjects who completed the study, 24 dominant eyes of 24 subjects were the primary subjects for analysis, excluding one subject who withdrew consent and eight subjects who did not comply with the protocol (Figure 2). Additionally, 48 eyes of 24 subjects were also analyzed for reference, including the bilateral mean values. The eight subjects who did not comply with the protocol included one subject who made a significant change to their lifestyle, resulting in a violation of the restrictions; four subjects for whom the measurement conditions for the objective examination were not consistent; and three subjects who, despite performing VDT work, experienced a decrease of 10% or more in HFC-1, i.e., significant improvements in indicators of focal function and eye strain, and for whom a doctor determined that they were not subjecting themselves to appropriate VDT load.

[0046] [Table 1] *1:VS: Vital signs *2: Leave at least 30 seconds between measurements of the right and left eyes. *3: A questionnaire survey will be conducted looking back over the three days prior to each visit. *4:0 Take one day's dose at night on the day of the week.

[0047] [Table 2]

[0048] [Table 3]

[0049] II results 1. Subject background Figure 2 shows the process from enrollment to analysis in this study. A screening test was conducted on 104 subjects to select them. Of these, 33 eligible subjects, aged 25 to 39 years, were selected for this study. Eligible subjects included 17 men and 16 women, with a mean age of 33.1 ± 3.97 years for men and 32.7 ± 4.95 years for women. One patient withdrew consent and eight patients who did not comply with the protocol were excluded. The 24 subjects included in the final analysis included 13 men and 11 women, with a mean age of 33.2 ± 4.11 years overall, 33.0 ± 3.94 years for men, and 33.4 ± 4.50 years for women (Table 4). The dominant eye was the right eye in 18 patients and the left eye in 6. The mean spherical equivalent of the dominant eye was -2.69±1.94D, the HFC-1 value was 55.02±4.23, and the accommodation response was 2.00±0.78 (Table 5).

[0050] 2.Accommodative function measurement test 1) Changes in HFC-1 (Table 6) No significant carryover effect was observed in the change in HFC-1. In the dominant eye, the change in HFC-1 from VDT stress before ingestion of the test food to rest after VDT stress (Figure 1, B-C interval: before and after rest) did not differ significantly between the test food groups (placebo group -0.40±4.05, test food group 0.49±2.71). After 4 weeks of test food ingestion, the change in HFC-1 in the dominant eye before and after rest was significantly lower in the test food group compared to the placebo group (placebo group 1.22±2.78, test food group -0.47±2.78, p<0.05). The change in HFC-1 in the dominant eye before and after rest is shown in Figure 3. There was no significant difference between the test food groups in the change in HFC-1 levels before and after resting for the left and right average before ingestion of the test food (placebo group -0.40±3.03, test food group 0.27±2.17).Furthermore, there was no significant difference in the change in HFC-1 levels before and after resting after 4 weeks of test food ingestion (placebo group 0.76±2.32, test food group 0.34±3.13, p=0.583).

[0051] 2) Change in regulatory response (Table 6) In the dominant eye, there was no significant difference between the test food groups in the change in accommodative response before and after VDT challenge (Figure 1, between A and B) or before and after rest (Figure 1, between B and C) before test food intake. Even after 4 weeks of test food intake, there was no significant difference between the test food groups in the change in accommodative response before and after VDT challenge or rest. However, in the test food intake group, there was a tendency for the change in accommodative response before and after rest to increase 4 weeks after intake (0.16 ± 0.52 D) compared to before intake (-0.10 ± 0.49 D). In the placebo group, there was a slight decrease 4 weeks after intake (-0.02 ± 0.37 D) compared to before intake (0.04 ± 0.49 D), and the increasing trend seen with the test food was not observed. There was no significant difference between the test food groups in the average change in accommodative response before and after VDT challenge and before and after rest before intake of the test food. Even after 4 weeks of test food intake, no significant differences were observed between the test food groups in the amount of change in accommodation response before and after VDT load or before and after rest.

[0052] 3) Changes in HFC-1 and accommodation response in the dominant eye before and after rest (number of eyes) (Table 7) The number of eyes with changes in HFC-1 in the dominant eye before and after rest is shown in Table 7. In the test food group, the number of eyes with an increase in HFC-1 before and after rest was 15 eyes before ingestion, but this decreased to 10 eyes after four weeks of ingestion. The number of eyes with a decrease in HFC-1 before ingestion was 9 eyes before ingestion, but increased to 14 eyes after four weeks of ingestion. In the placebo group, the number of eyes with an increase in HFC-1 before and after rest was 14 eyes before ingestion, but increased to 19 eyes after four weeks of ingestion. The number of eyes with a decrease in HFC-1 before ingestion was 10 eyes before ingestion, but decreased to 5 eyes after four weeks of ingestion.

[0053] 3. Medical record questionnaire In the medical record questionnaire, no significant differences were observed between the test food group and the placebo group in the differences before and after intake and between week 0 and week 4 after intake (Table 8).

[0054] 4. Diary survey Table 9 shows the analysis results of the diary questionnaire. In the questionnaire, a comparison between the test food group and the placebo group revealed significant improvement in symptoms in the test food group compared to the placebo group after four weeks of test food intake, including 1. eye fatigue (placebo group 2.46±0.83, test food group 2.79±0.88, p<0.05), 5. eye redness (placebo group 3.42±1.21, test food group 3.58±1.25, p<0.05), and the total questionnaire score (placebo group 38.83±9.41, test food group 40.38±8.85, p<0.05). Figure 4 shows the results of extracting diary questionnaire items that showed significant differences between the test food groups.

[0055] 5. Adverse Events No adverse events thought to be caused by the test food were observed during the study period, and no subjects experienced any significant lifestyle changes during the study period.

[0056] [Table 4]

[0057] [Table 5]

[0058] [Table 6]

[0059] [Table 7]

[0060] [Table 8]

[0061] [Table 9] TIFF2026020077000013.tif3655 Values ​​are mean ± SD Comparison between test food groups: *p<0.05

[0062] III Discussion The results of this study focused on focus accommodation and ciliary muscle tone due to VDT load, and examined the effectiveness and safety of a compound supplement containing lactic acid bacteria WB2000, resveratrol, and crocetin. HFC, which is an evaluation item for focus accommodation and an indicator of eye fatigue, was improved, and improvements in eye fatigue and overall eye symptoms were observed. This suggests that the test food is effective against eye fatigue both objectively and subjectively. One of the ingredients in this test food, lactic acid bacteria WB2000, is a strain of Enterococcus faecium isolated from healthy individuals. It has been reported that use of toothpaste containing WB2000 induces an oral environment less prone to dental caries and increases tear production, improving dry eye symptoms. WB2000's approach to dry eye, one of the two major causes of digital eye strain, may also have improved symptoms. The significant improvement in eye redness measured by the daily questionnaire after the test food treatment may have been due to increased tear production, in addition to eye strain. In subjects who are aware of eye strain (eye fatigue) on a daily basis and work at a VDT for 4 hours or more per day, HFC-1 levels increased even when the VDT work did not place a high level of accommodation strain on the subject at the time of their visit, and the intake of the test food product improved the change in HFC-1 levels before and after rest. Furthermore, in the diary questionnaire, in addition to the two points of eye fatigue and eye redness, the intake of the test food product also showed a significant improvement in the total score of the diary questionnaire. As described above, the effectiveness of the composition of the present invention in reducing the decrease in focusing function due to eye fatigue, both objectively and subjectively, suggests that the composition of the present invention may have had a synergistic effect not only with crocetin but also with lactic acid bacteria WB2000 and resveratrol. [Industrial Applicability]

[0063] A randomized, placebo-controlled, double-blind study evaluated the efficacy and safety of a test food containing lactic acid bacteria WB2000, resveratrol, and crocetin in VDT ​​users who regularly experience eye strain. The results suggested that the food may be effective in treating reduced focusing function caused by eye strain. It was also confirmed that there were no safety issues.

Claims

1. An oral composition for preventing or improving impaired focusing ability, comprising at least one component selected from the group consisting of resveratrol and crocetin, and the lactic acid bacterium Enterococcus faecium.

2. 10. The composition of claim 1, which is a pharmaceutical composition.

3. The composition according to any one of claims 1 to 2, which is a food composition.

4. The composition according to any one of claims 1 to 3, wherein the impaired focusing ability is impaired focusing ability due to VDT syndrome, presbyopia or eye strain.

5. An oral composition for improving eye fatigue or eye redness, comprising at least one component selected from the group consisting of resveratrol and crocetin, and lactic acid bacteria Enterococcus faecium.

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