JP7367956B2 - Composition for improving dynamic vision - Google Patents

Description

The present invention relates to a composition for improving dynamic visual acuity.

Among human senses, vision is said to be responsible for over 80% of external information, making it the most important sense. Maintaining good vision is an extremely important issue in a super-aging society. Particularly recently, the rapidly increasing number of traffic accidents caused by elderly drivers has become a major social problem. Generally, resting visual acuity is measured in visual acuity tests, but when you are driving a car, playing sports, playing games, etc., your visual ability to instantly track and see moving objects is important as well as your resting visual acuity. This is called dynamic visual acuity (dynamic visual function). Dynamic visual acuity in humans is important for things such as driving and sports ability, but it has rarely been studied until now because a decline in its function or abnormality does not cause disease. In the process of conducting retinal vision research, the present inventors improved the dynamic visual function analysis method used in monkeys and other animals, and objectively and quantitatively analyzed the dynamic visual acuity (spatial discrimination ability, temporal discrimination ability, contrast ability) of mice. We have developed a technology that can measure visual acuity (discrimination ability) (Non-Patent Document 1), and are searching for substances that enhance human dynamic visual acuity.

Among the foods and drinks that are familiar to us, matcha contains many physiologically active substances. Among them, catechins, which are abundantly contained in green tea, have been reported to have neuroprotective effects. There is also a report that the more people drink green tea, the less damage their retinas receive from ultraviolet rays (Non-Patent Document 2). The effects of green tea on glaucoma and other eye diseases have also been reported. For example, since green tea has a protective effect on the retina in rats (Non-Patent Document 3), green tea is also expected to prevent eye diseases. These reports suggest that ingesting catechins, which are abundant in matcha, may maintain good vision, but there have been no reports on how catechins affect visual function.

Sugita Y, Miura K, Araki F, Furukawa T, Kawano K. Contributions of retinal direction-selective ganglion cells to optokinetic responses in mice. Eur J Neurosci. 2013, 38(6): 2823-31. Xu JY, Zheng XQ, Lu JL, Wu MY, Liang YR. Green tea polyphenols attenuating ultraviolet B-induced damage to human retinal pigment epithelial cells in vitro. Invest Ophthalmol Vis Sci 2010; 51: 6665-70. Chu KO, Chan KP, Wang CC, Chu CY, Li WY, Choy KW, Roger MS, Pang CP. Green tea catechins and their oxidative protection in the rat eye. J Agric Food Chem 2010; 58: 1523-34.

An object of the present invention is to provide a novel composition for improving dynamic visual acuity and a novel drug for improving dynamic visual acuity.

The present invention includes the following inventions to solve the above problems.
[1] A composition for improving dynamic visual acuity containing tea leaves or tea leaf extract as an active ingredient.
[2] The composition according to [1] above, wherein the tea leaf extract contains epigallocatechin gallate.
[3] The composition according to [1] or [2] above, wherein the improvement in dynamic object visual acuity is an improvement in the ability to discriminate the speed of a moving object.
[4] The composition according to any one of [1] to [3] above, which is a food or drink.
[5] A drug for improving dynamic visual acuity containing epigallocatechin gallate as an active ingredient.
[6] The composition according to [5] above, wherein the improvement in dynamic body visual acuity is an improvement in the ability to discriminate the speed of a moving body.

According to the present invention, a novel composition for improving dynamic visual acuity and a novel drug for improving dynamic visual acuity can be provided. The composition and medicament of the present invention can particularly improve the ability to discriminate moving body speed.

An explanatory diagram of the visual stimulus used in the optokinetic response measurement. The upper row is an explanatory diagram of the spatial frequency and temporal frequency of the vertical sinusoidal stripes used, and the lower row is an illustration of the period from stimulus start to stimulus end in one trial. It is an explanatory diagram. FIG. 2 is a diagram of the apparatus used in optokinetic response measurement. FIG. 2 is a diagram showing the results of fitting the average speed of the optokinetic response of each group in Example 1 using a Gaussian function, in which (A) is the control group, (B) is the matcha group, and (C) is the sencha group. , (D) is a plot of the optimal spatiotemporal frequency for each mouse. FIG. 3 is a diagram showing the results of optokinetic response measurement in Example 1, in which (A) is the optimal spatial frequency [cycle/deg], (B) is the optimal temporal frequency [Hz], and (C) is the response strength [ deg/s] (how much it moves in one second), (D) is the optimal speed [deg/s], and (E) is the result of the gain. FIG. 2 is a diagram showing the results of fitting the average velocity of the optokinetic response before and after administration of epigallocatechin gallate in Example 2 with a Gaussian function, (A) before administration of epigallocatechin gallate, (B) ) is a plot of the optimal spatiotemporal frequency of each mouse after epigallocatechin gallate administration, and (C) is a plot of the optimal spatiotemporal frequency of each mouse. FIG. 3 is a diagram showing the results of optokinetic response measurement in Example 2, in which (A) is the optimal spatial frequency [cycle/deg], (B) is the optimal temporal frequency [Hz], and (C) is the response strength [ deg/s] (how much it moves in one second), (D) is the optimal speed [deg/s], and (E) is the result of the gain.

The present invention provides a composition for improving dynamic visual acuity containing tea leaves or a tea leaf extract as an active ingredient. Tea leaves refer to the leaves of Camellia sinensis, an evergreen tree belonging to the Camellia family, and may include buds and stems. The tea leaves may be raw tea leaves or may be processed for drinking. Treatment of tea leaves includes unfermented, semi-fermented, and highly fermented, and any of these treatments may be used. Unfermented teas include green tea (sencha, gyokuro, kabusecha, bancha, tamaryokucha, matcha, hojicha, kamairicha, tencha, etc.); semi-fermented teas include oolong tea and pouchongcha; fermented teas include black tea and pu-erh. One example is tea. The tea leaves may be used after being cut into pieces, or may be used after being made into powder. The tea leaves or tea leaf extracts that are the active ingredients of the composition of the present invention are preferably green tea leaves or green tea leaf extracts.

When the composition of the present invention contains a tea leaf extract as an active ingredient, the tea leaf extract preferably contains epigallocatechin gallate. The present inventors have confirmed that dynamic visual acuity is improved even when epigallocatechin gallate is administered alone to mice.

The tea leaf extract can be obtained by extracting tea leaves with a solvent, and a conventionally known method can be used. Tea leaves may be pulverized before extraction. Extraction solvents include water, hydrophilic solvents, or mixtures thereof. Examples of the hydrophilic solvent include lower alcohols such as methanol, ethanol, propyl alcohol, and isopropyl alcohol, lower aliphatic ketones such as acetone and methyl ethyl ketone, and polyhydric alcohols such as 1,3-butylene glycol, propylene glycol, and glycerin. be able to. The extraction solvent may be water or an aqueous ethanol solution, or may be water. The concentration of ethanol in the ethanol aqueous solution is not particularly limited, but may be 70% by weight or less. When extracting with water, the extraction temperature may be 60-100°C, 65-95°C, or 70-80°C. The extraction time may be 5 to 60 minutes. Regarding the weight ratio of water to tea leaves, water may be used in an amount of 10 times or more the dry weight of tea leaves, or 10 to 100 times the dry weight of tea leaves. After the extraction process, the tea leaf extract may be subjected to a process such as filtration or centrifugation to remove solid content. Furthermore, treatments such as concentration and drying may be performed.

The composition of the present invention can be used to improve dynamic visual acuity. Dynamic visual acuity is visual acuity that allows you to continuously identify moving objects without taking your line of sight. ), contrast discrimination ability of a moving object (contrast discrimination ability), etc. The composition of the present invention improves the ability to discriminate the speed of a moving object in terms of visual acuity, and further improves the speed of the eye tracking a moving object (strength of reaction), the speed of the moving object that is easiest to identify (optimal speed), and the ability of the eye to identify moving objects. The inventors of the present invention have confirmed that the ratio (gain) that can be followed is improved.

The composition of the present invention can be suitably used as a food or drink. Food and beverages include health foods, foods with functional claims, foods for specified health uses, foods for the sick, nutritionally fortified foods, supplements, etc. The form of the food and drink is not particularly limited. For example, in the form of tablets, granules, powders, drinks, etc.; beverages such as tea drinks, soft drinks, carbonated drinks, nutritional drinks, fruit drinks, lactic acid drinks; candies, candies, gums, chocolates, snacks, biscuits, jellies, etc. Sweets and breads such as jams, creams, baked goods, and bread; Processed seafood and livestock foods such as kamaboko, ham, and sausage; Dairy products such as processed milk and fermented milk; Salad oil, tempura oil, margarine, mayonnaise, shortening, and whipped cream. Fats and oil-processed foods such as creams and dressings; seasonings such as sauces and sauces; retort pouch foods such as curry, stew, rice bowls, porridge, and porridge; frozen desserts such as ice cream, sherbet, and shaved ice. .

The content of the active ingredient in the composition of the present invention is not particularly limited, and may be 0.01 to 99% (w/w), or 0.1 to 95% (w/w). .

The present invention provides a drug for improving dynamic visual acuity containing epigallocatechin gallate as an active ingredient. Epigallocatechin gallate can be produced, for example, by extracting and purifying green tea leaves (Japanese Unexamined Patent Publication No. 2001-97968, etc.). Alternatively, commercially available products such as Teavigo (registered trademark, Taiyo Kagaku Co., Ltd.) may be used.

The medicament of the present invention can be formulated by appropriately blending the active ingredient epigallocatechin gallate with a pharmaceutically acceptable carrier or additive. Specifically, oral preparations such as tablets, coated tablets, pills, powders, granules, capsules, solutions, suspensions, and emulsions; injections, infusions, suppositories, ointments, patches, enteral nutrition, etc. It can be used as a parenteral preparation. The blending ratio of carriers or additives may be appropriately set based on the range normally employed in the pharmaceutical field. The carriers or additives that can be incorporated are not particularly limited, but include various carriers such as water, physiological saline, other aqueous solvents, aqueous or oily bases; excipients, binders, pH adjusters, disintegrants, and absorbents. Examples include various additives such as accelerators, lubricants, colorants, flavoring agents, and fragrances.

Examples of additives that can be incorporated into tablets, capsules, etc. include gelatin, cornstarch, tragacanth, binders such as gum arabic, excipients such as crystalline cellulose, cornstarch, gelatin, alginic acid, etc. leavening agents such as magnesium stearate, lubricants such as magnesium stearate, sweetening agents such as sucrose, lactose or saccharin, flavoring agents such as peppermint, redwood oil or cherry, and the like. When the dosage unit form is a capsule, materials of the above type can additionally contain a liquid carrier such as an oil or fat. Sterile compositions for injection can be prepared according to conventional pharmaceutical procedures, such as dissolving or suspending the active ingredient in a solvent such as water for injection, natural vegetable oils, or the like. Examples of aqueous solutions for injection include physiological saline, isotonic solutions containing glucose and other adjuvants (e.g., D-sorbitol, D-mannitol, sodium chloride, etc.), and appropriate solubilizing agents. For example, it may be used in combination with alcohol (eg, ethanol), polyalcohol (eg, propylene glycol, polyethylene glycol), nonionic surfactant (eg, polysorbate 80TM, HCO-50), and the like. As the oily liquid, sesame oil, soybean oil, etc. are used, and may be used in combination with solubilizing agents such as benzyl benzoate and benzyl alcohol. Also, buffering agents (e.g., phosphate buffer, sodium acetate buffer), soothing agents (e.g., benzalkonium chloride, procaine hydrochloride, etc.), stabilizers (e.g., human serum albumin, polyethylene glycol, etc.), preservatives, etc. It may also be blended with agents (eg, benzyl alcohol, phenol, etc.), antioxidants, and the like.

When the pharmaceutical of the present invention is administered to humans, the dose of epigallocatechin gallate depends on the dosage form and the age of the patient, but may be in the range of 1 mg to 1,000 mg per day. It may be within the range of 10 mg to 500 mg.

The medicament of the present invention is useful as a medicament for improving dynamic visual acuity. The medicine of the present invention improves the ability to discriminate the speed of a moving object in terms of visual acuity, and also improves the speed of the eye to follow a moving object (strength of reaction) and the speed of the moving object that is easiest to identify (optimal speed). , has been confirmed by the present inventors.

EXAMPLES Hereinafter, the present invention will be explained in detail with reference to Examples, but the present invention is not limited thereto.

[Example 1: Effects of matcha and sencha on visual function]
1. Materials and methods (1) Experimental animals
C57/BL6J mice (2 months old, male, weight 20-30 g) were used. Mice were housed in an animal room maintained at a room temperature of 20–26°C, humidity of 30–70%, and a 12-h dark/light cycle. For the normal feed, Labo MR Stock (Nippon Agricultural Industry Co., Ltd.), a feed for raising and breeding mice, was given, and for the feed containing matcha and sencha, Labo MR Stock (Nippon Agricultural Industry Co., Ltd.) was given. Matcha and sencha were provided by the Nestlé Matcha and Health Research Group. Feed and water were available ad libitum. The experiment was conducted in accordance with the Osaka University Animal Experiment Practice Regulations.

(2) Experimental group Control group (n=5): Regular feed was given for one month.
Matcha group (n=5): Feed containing 2% matcha was given for 1 month.
Sencha group (n=5): Feed containing 2% Sencha for 1 month.
The optomotor response was measured after feeding the matcha-containing diet and the matcha-containing diet for 1 month.

(3) Optokinetic response measurement Visual stimuli were created using MATLAB/Psychtoolbox (Brainard DH. The Psychophysics Toolbox. Spatial Vision. 1997; 10: 433-36.) and presented on monitors placed on three sides around the mouse. The visual stimulus used was a sine wave stripe. We investigated the spatiotemporal characteristics by changing the spatial and temporal frequencies of the parameters of the sinusoidal fringe stimulation. Spatial frequency (SF) is the fineness of the stripes when a visual stimulus moves, and temporal frequency (TF) is the speed at which the stripes move. The spatial frequency was varied in 5 types: SF=0.0313, 0.0625, 0.125, 0.25, 0.5 cycle/degree, and the temporal frequency was varied in 8 types: TF=0.1875, 0.375, 0.75, 1.5, 3, 6, 12, 24 Hz ( (see Figure 1).

A stationary stripe stimulus pattern was presented on the monitor at the beginning of each trial. A stationary pattern was presented for 333 ms, after which the pattern moved either to the left or to the right for 30 s. After the pattern moved, the screen changed to a solid gray screen and the trial ended. The next trial began 2 seconds later. Each trial stimulation condition was randomly selected from 62 types (31 types x 2 directions) of stimulation conditions (see Figure 1).

Eye movements of the mouse's right eye were measured while presenting moving visual stimuli. A head holder was attached to the mouse's skull with dental cement under ketamine anesthesia. During the experiment, to minimize mouse movement, the head was fixed by screwing the head holder to a stainless steel rod, and the body was also fixed in a small case. An infrared light was shined on the mouse's right eye, and a hot mirror was placed at a position 60 degrees from the mouse's body axis (see Figure 2). The image of the mouse's right eye reflected by the hot mirror was recorded every 5 milliseconds with an infrared sensing camera (CCD camera) (sampling rate: 200Hz). The hot mirror reflects infrared light but allows visible light to pass through, allowing the mouse to see visual stimuli on a monitor behind the hot mirror.

Eye position data was obtained by analyzing mouse eye images using software (GetEye). The position of the center of gravity of the pupil is calculated from momentary images of the mouse eye. The position of the eyes (direction of line of sight) was calculated based on the position of the center of gravity of the pupil. Calibration of the eyeball position was performed as follows. A mouse eyeball model (Remtulla S, Hallett PE. A schematic eye for the mouse, and comparisons with the rat. Vision Res 1985; 25: 21-31.) was placed in the same position as the mouse eyeball during the experiment, and the left and right The position of the pupil center of gravity on the image when rotated by 2 degrees in each direction up to 10 degrees was recorded. Based on this data, the correspondence between the position of the pupil center of gravity on the image and the position of the mouse's eye (direction of line of sight) was determined, and the position of the mouse's eye was calculated. Eye velocity was then calculated by differentiating the eye position data. For each trial, the average eye velocity for 30 seconds after the onset of the stimulus was measured, and this was taken as the magnitude of the evoked eye movement response. Data analysis was performed using MATLAB (MathWorks, MA).

2. Results Figure 3 shows the magnitude of the average velocity of the optokinetic response of each group fitted with a Gaussian function. (A) is the control group, (B) is the matcha group, and (C) is the sencha group. The vertical axis shows temporal frequency, and the horizontal axis shows spatial frequency. A plot of the optimal spatiotemporal frequency for each mouse is shown in the upper right (D). In all experimental groups, the response was weak when the spatial and temporal frequencies were too low or too high. Compared to the control group, mice in the matcha and sencha groups were found to have a higher optimal temporal frequency. As a result of finding the best-fitting Gaussian function from the data of each of the five animals, in the control group, the largest eye movement response was observed when the spatial frequency was 0.157±0.03 [cycle/deg] and the temporal frequency was 1.03±0.15 [Hz]. It was done. In the matcha group, the optimal frequency was a spatial frequency of 0.161±0.01 [cycle/deg] and a temporal frequency of 1.40±0.35 [Hz]. In the Sencha group, the optimal frequency was a spatial frequency of 0.147±0.01 [cycle/deg] and a temporal frequency of 1.40±0.24[Hz]. These results suggested that there is an optimal spatiotemporal frequency for eliciting optomotor responses in each group.

Figure 4 shows (A) optimal spatial frequency [cycle/deg], (B) optimal temporal frequency [Hz], (C) reaction strength [deg/s] (how much movement per second) for each group. The results of (D) optimal speed [deg/s] and (E) gain are shown. (A) is the ability to discern the fineness of a moving object, (B) is the ability to discern the speed of a moving object, (C) is the speed of the eye following a moving object, and (D) is the easiest to identify. This is the speed of the moving object, and (E) is the rate at which the eyes can follow the moving object. It was shown that the temporal frequency was significantly higher in the matcha and sencha groups than in the control group. In addition, the response strength, optimal speed, and gain were significantly higher, and it became clear that the response to objects moving at fast speeds was greater.

[Example 2: Effect of epigallocatechin gallate (EGGC) on visual function]
1. material and method
Five C57/BL6J mice (2 months old, male, weight 20-30 g) were used. EGGC (Nacalai Tesque, manufacturer: Nagara Science Co., Ltd.) was dissolved in physiological saline at a concentration of 10 mg/ml, and EGCG was intraperitoneally administered at a dose of 50 mg/kg for 4 days. Before administration of EGGC and after administration of EGGC for 4 days, optomotor responses were measured in the same manner as in Example 1.

2. Results Figure 5 shows the magnitude of the average velocity of the optomotor response before and after EGCG administration, which was fitted with a Gaussian function. The vertical axis shows temporal frequency, and the horizontal axis shows spatial frequency. As in Example 1, both before and after EGCG administration, the response was weak whether the spatial frequency or temporal frequency was too low or too high. The optimal spatiotemporal frequency for each mouse is shown in the upper right. It was found that the optimal temporal frequency was higher in mice after EGCG administration than before EGCG administration. As a result of finding the best-fitting Gaussian function from the data of each 5 animals, we found that before EGCG administration, the largest eye movement response was at a spatial frequency of 0.16±0.01 [cycle/deg] and a temporal frequency of 1.06±0.04 [Hz]. Observed. After EGCG administration, the optimal frequencies were a spatial frequency of 0.16±0.02 [cycle/deg] and a temporal frequency of 1.29±0.11 [Hz].

Figure 6 shows (A) optimal spatial frequency [cycle/deg], (B) optimal temporal frequency [Hz], and (C) response strength [deg/s] (how much movement per second) before and after EGCG administration. , (D) optimal speed [deg/s], and (E) gain results. It was shown that the temporal frequency was significantly higher after EGCG administration than before EGCG administration. In addition, the strength of the reaction and the optimal speed were significantly higher, and it became clear that the reaction was greater for objects that moved at fast speeds.

It should be noted that the present invention is not limited to the embodiments and examples described above, and various changes can be made within the scope of the claims, and technical means disclosed in different embodiments can be combined as appropriate. The resulting embodiments also fall within the technical scope of the present invention. Additionally, all academic and patent documents mentioned herein are incorporated by reference herein.

Claims (3)

A composition for improving dynamic vision containing epigallocatechin gallate as an active ingredient (however, tea leaf extracts or tea leaves that have been subjected to enzyme treatment and/or acid hydrolysis treatment to convert kaempferol glycosides to kaempferol aglycones) (excluding those containing processed products) . The composition according to claim 1 , wherein the improvement in dynamic object visual acuity is an improvement in the ability to discriminate the speed of a moving object. The composition according to claim 1 or 2 , which is a food or drink.