Dynamic visual acuity-enhancing composition

Abstract

To provide a dynamic visual acuity-enhancing composition.SOLUTION: Provided is a dynamic visual acuity-enhancing composition containing cassis anthocyanin as an active ingredient and improving dynamic visual acuity, particularly dynamic contrast discriminability.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a composition for improving dynamic visual acuity. [Background technology]

[0002] Human vision is said to be responsible for over 80% of external information and is the most important of all senses. Maintaining good vision is an extremely important issue in a super-aging society. In particular, the recent sharp increase in traffic accidents caused by elderly drivers has become a major social issue. Generally, visual acuity tests measure static visual acuity, but when driving a car, playing sports, or playing games, in addition to static visual acuity, the visual function of instantly tracking and seeing moving objects is also required; this is called dynamic visual acuity (dynamic visual function). Human dynamic visual acuity is important for driving and sports ability, but because its decline or abnormality does not cause illness, it has received little research to date.

[0003] In the course of their retinal vision research, the present inventors have improved the dynamic visual function analysis method previously used in monkeys and other animals, developed a technique that can objectively and quantitatively measure the dynamic visual acuity (spatial discrimination ability, speed discrimination ability, and contrast discrimination ability) of mice (Non-Patent Document 1), and are searching for substances that enhance human dynamic visual acuity. The present inventors have previously found that administering tea leaf extract containing epigallocatechin gallate to mice improves dynamic visual acuity (Patent Document 1). The present inventors have also found that administering eugenol, which is abundant in essential oils such as clove, to mice improves their ability to discriminate between moving objects' speeds, and have filed a patent application for this finding (Patent Document 2). [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Patent Publication No. 2021-011449 [Patent Document 2] International Publication WO2022 / 255282A1 [Non-patent literature]

[0005] [Non-Patent Document 1] 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): 2823-2831. Summary of the Invention [Problem to be solved by the invention]

[0006] An object of the present invention is to provide a composition for improving dynamic visual acuity. [Means for solving the problem]

[0007] The present invention includes the following inventions to solve the above problems. [1] A composition for improving dynamic visual acuity containing blackcurrant anthocyanin as an active ingredient. [2] The composition described in [1] above, wherein the blackcurrant anthocyanin is at least one selected from the group consisting of delphinidin-3-O-rutinoside and cyanidin-3-O-rutinoside. [3] The composition according to [1] or [2], wherein the improvement in dynamic visual acuity is an improvement in dynamic contrast discrimination ability. [4] The composition described in [1] or [2] above, which is a food or drink. [Effects of the Invention]

[0008] The present invention provides a novel composition for improving dynamic visual acuity, which is particularly effective in improving contrast discrimination ability for moving objects. [Brief explanation of the drawings]

[0009] [Figure 1]This is an explanatory diagram of the visual stimuli used in measuring optokinetic responses. (A) is an explanatory diagram of the spatial frequency (width of the stripes) and temporal frequency (speed of the stripes) of the vertical sinusoidal stripes used to measure spatiotemporal frequency sensitivity. (B) is an explanatory diagram of the visual stimuli used to measure contrast sensitivity. (C) is an explanatory diagram of the process from the start to the end of a single trial. [Figure 2] FIG. 1 is a diagram of the apparatus used in optokinetic response measurements. [Figure 3] This figure shows the results of fitting the magnitude of the average speed of the optokinetic response with a Gaussian function for each group in Example 1. (A) is the control group, (B) is the black currant extract group, (C) is the black currant powder group, and (D) is a plot of the optimal spatiotemporal frequency for each mouse. The vertical axis represents the temporal frequency (Hz), and the horizontal axis represents the spatial frequency (cycles / deg). [Figure 4] 1 shows the results of the spatiotemporal frequency characteristic measurement in Example 1. (A) shows the optimal spatial frequency [cycle / deg], (B) shows the optimal temporal frequency [Hz], (C) shows the strength of the response [deg / s] (how much movement there is per second), (D) shows the optimal speed [deg / s], and (E) shows the gain. [Figure 5] 1 shows the results of contrast sensitivity measurement in Example 1. (A) shows the control group, (B) shows the black currant extract group, (C) shows the black currant powder group, and (D) shows the average of each mouse group. The vertical axis shows eye velocity (deg / s), and the horizontal axis shows contrast (%). [Figure 6] This figure shows the results of fitting the magnitude of the average velocity of the optokinetic response of each group in Example 2 with a Gaussian function. (A) is the control group, (B) is the D3R group, (C) is the C3R group, and (D) is a plot of the optimal spatiotemporal frequency for each mouse. The vertical axis represents the temporal frequency (Hz), and the horizontal axis represents the spatial frequency (cycles / deg). [Figure 7] 1 shows the results of the spatiotemporal frequency characteristic measurement in Example 2. (A) shows the optimal spatial frequency [cycle / deg], (B) shows the optimal temporal frequency [Hz], (C) shows the strength of the response [deg / s] (how much movement there is per second), (D) shows the optimal speed [deg / s], and (E) shows the gain. [Figure 8]1 shows the results of contrast sensitivity measurement in Example 2. (A) shows the control group, (B) shows the D3R group, (C) shows the C3R group, and (D) shows the average of each mouse group. The vertical axis shows eye velocity (deg / s), and the horizontal axis shows contrast (%). [Figure 9] 1 is a diagram showing the results of contrast sensitivity shown in Examples 1 and 2. The vertical axis represents eye velocity (deg / s) and the horizontal axis represents contrast (%). DETAILED DESCRIPTION OF THE INVENTION

[0010] The present invention provides a composition for improving dynamic visual acuity, containing blackcurrant anthocyanin as an active ingredient. Anthocyanin is a type of polyphenol, a water-soluble pigment that is responsible for the reddish-purple and bluish-purple colors found in vegetables, fruits, and flowers. Anthocyanins are found in large quantities in berries such as blackcurrant, eggplant, and purple sweet potato. Blackcurrant, also known as gooseberry or blackcurrant, is a deciduous shrub of the Ribes genus in the Saxifragaceae family and is a type of berry that bears deep purple fruits approximately 1 cm in diameter. In the present invention, "blackcurrant anthocyanin" may be any anthocyanin contained in blackcurrant. Preferably, it is an anthocyanin contained in blackcurrant fruit. Blackcurrant is known to contain four types of anthocyanins: delphinidin-3-rutinoside (D3R), delphinidin-3-glucoside (D3G), cyanidin-3-rutinoside (C3R), and cyanidin-3-glucoside (C3G). Of these, the rutinosides D3R and C3R are compounds not found in other berries.

[0011] When the composition of the present invention contains blackcurrant anthocyanin as an active ingredient, the method for producing the blackcurrant anthocyanin is not particularly limited. In the present invention, the blackcurrant anthocyanin may be a blackcurrant extract (blackcurrant extract) or a dried product thereof (dried extract), or may be delphinidin-3-rutinoside (D3R), delphinidin-3-glucoside (D3G), cyanidin-3-rutinoside (C3R), cyanidin-3-glucoside (C3G), or any combination thereof. Blackcurrant extract or at least one selected from the group consisting of D3R and C3R is preferred. At least one selected from the group consisting of D3R and C3R is more preferred. D3R is even more preferred. In the present invention, the blackcurrant extract is preferably an extract of blackcurrant fruit. Blackcurrant extract can be obtained by extracting blackcurrant fruit juice using, for example, a column or solvent, and conventionally known methods can be used. When the composition of the present invention contains black currant extract as an active ingredient, the black currant extract preferably contains at least one selected from the group consisting of D3R and C3R. The present inventors have confirmed that administering D3R or C3R alone to mice improves dynamic visual acuity.

[0012] In the present invention, blackcurrant anthocyanin may be produced by, for example, extraction from blackcurrant fruit and purification, or commercially available blackcurrant anthocyanin may be used. For example, commercially available blackcurrant anthocyanin may be obtained and processed and used, such as "Blackcurrant Extract MJ" (trade name) from Morishita Jintan Co., Ltd., "Meiji Blackcurrant Polyphenol (AC10)" (trade name) from Meiji Food Material Co., Ltd., "Blackcurrant Extract Powder" (trade name) from Matsuura Pharmaceutical Co., Ltd., "Blackcurrant Extract-35" (trade name) and "Casinol (registered trademark)" (trade name) from Tama Biochemical Co., Ltd., "Blackcurrant Extract" (trade name) from Just the Berries Co., Ltd., "Blackcurrant Extract" (trade name) from Best Grand Co., Ltd., and "Blackcurrant Extract" (trade name) from Keien Japan Co., Ltd.

[0013] The composition of the present invention can be used to improve dynamic visual acuity. Dynamic visual acuity is the ability to continuously distinguish a moving object without averting one's line of sight, and includes the ability to distinguish the speed of a moving object (time discrimination ability), the ability to distinguish the fineness of a moving object (spatial discrimination ability), and the ability to distinguish the contrast of a moving object (contrast discrimination ability). The present inventors have confirmed that the composition of the present invention improves dynamic visual acuity, particularly dynamic contrast discrimination ability.

[0014] The subject to which the composition of the present invention is applied is not particularly limited, and can be, for example, mammals such as humans, monkeys, mice, rats, rabbits, dogs, cats, horses, cows, and pigs. Humans are preferred. The subject to which the composition of the present invention is applied may be in childhood, youth, middle age, or old age. When the subject is a human, the subject may be under 20 years old, 20 years old or older, 30 years old or older, 40 years old or older, 50 years old or older, 60 years old or older, 70 years old or older, or 80 years old or older. It is known that dynamic visual acuity develops as we grow, peaking at age 20 in humans and then declining thereafter. Therefore, the composition of the present invention can be used to improve age-related decline in dynamic visual acuity.

[0015] The composition of the present invention can be suitably embodied as a food or beverage. Examples of such food or beverage include health foods, functional foods, foods for specified health uses, foods for the sick, nutritionally fortified foods, and supplements. The form of the food or beverage is not particularly limited. Examples include tablets, granules, powders, and energy drinks; beverages such as tea drinks, soft drinks, carbonated drinks, nutritional drinks, fruit drinks, and lactic acid drinks; sweets and breads such as candy, candy, gum, chocolate, snacks, biscuits, jellies, jams, cream, baked goods, and bread; processed seafood and livestock foods such as kamaboko (fish cake), ham, and sausage; dairy products such as processed milk and fermented milk; oils and fats and processed oil foods such as salad oil, tempura oil, margarine, mayonnaise, shortening, whipped cream, and dressing; condiments such as sauces and dressings; retort pouch foods such as curry, stew, rice bowls, porridge, and rice porridge; and frozen desserts such as ice cream, sherbet, and shaved ice.

[0016] The content of blackcurrant anthocyanins 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).

[0017] The composition of the present invention can be suitably used as a pharmaceutical. The pharmaceutical of the present invention can be formulated by appropriately blending cassis anthocyanins, the active ingredient, with pharmaceutically acceptable carriers or additives. Specifically, the pharmaceutical can be formulated as oral preparations such as tablets, coated tablets, pills, powders, granules, capsules, liquids, suspensions, and emulsions; or parenteral preparations such as injections, infusions, suppositories, ointments, patches, and enteral nutrients. The blending ratio of the carrier or additive may be appropriately determined based on the range commonly used in the pharmaceutical field. The carrier or additive that can be blended is not particularly limited, and examples thereof include various carriers such as water, physiological saline, other aqueous solvents, and aqueous or oily bases; and various additives such as excipients, binders, pH adjusters, disintegrants, absorption enhancers, lubricants, colorants, flavorings, and fragrances.

[0018] Examples of additives that can be incorporated into tablets, capsules, etc. include binders such as gelatin, corn starch, tragacanth, and gum arabic, excipients such as crystalline cellulose, leavening agents such as corn starch, gelatin, and alginic acid, lubricants such as magnesium stearate, sweeteners such as sucrose, lactose, or saccharin, and flavors such as peppermint, saffron oil, and cherry. When the dosage unit form is a capsule, a liquid carrier such as oil or fat may be further contained in addition to the above-mentioned materials. Sterile compositions for injection can be prepared according to conventional pharmaceutical procedures (for example, by dissolving or suspending the active ingredient in a solvent such as water for injection or natural vegetable oil). Examples of aqueous solutions for injection include physiological saline, isotonic solutions containing glucose or other adjuvants (e.g., D-sorbitol, D-mannitol, sodium chloride, etc.), and the like, which may be used in combination with appropriate solubilizers such as alcohols (e.g., ethanol), polyalcohols (e.g., propylene glycol, polyethylene glycol), and nonionic surfactants (e.g., Polysorbate 80™, HCO-50). Examples of oily solutions include sesame oil and soybean oil, which may be used in combination with solubilizers such as benzyl benzoate and benzyl alcohol. Furthermore, the injection may also contain buffers (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 (e.g., benzyl alcohol, phenol, etc.), antioxidants, etc.

[0019] When the pharmaceutical of the present invention is administered to humans, the dose of blackcurrant anthocyanins depends on the dosage form, the age of the patient, etc., but may be in the range of 1 mg to 1000 mg per day, 10 mg to 500 mg per day, or 10 mg to 100 mg per day. [Example]

[0020] The present invention will be described in detail below with reference to examples, but the present invention is not limited to these examples.

[0021] Example 1: Effect of black currant on visual function in mice 1. Materials and Methods (1) Experimental animals C57 / BL6J mice (21-month-old males, weighing 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-hour light-dark cycle. Regular diet was provided: Lab MR Stock (Nihon Nokogyo Co., Ltd.), a mouse breeding diet. Diet containing black currant extract or black currant powder was provided: Lab MR Stock (Nihon Nokogyo Co., Ltd.), containing black currant extract or black currant powder. Black currant extract and black currant powder were manufactured by Morishita Jintan Co., Ltd. Food and water were available ad libitum. Experiments were conducted in accordance with the Osaka University Animal Experimentation Regulations.

[0022] (2) Experimental group Control group (n=5): Normal feed was given for one month. Blackcurrant extract group (n=5): Rats were given a diet containing 2% blackcurrant extract for one month. Black currant powder group (n=5): Rats were given a diet containing 2% black currant powder for one month. After feeding the mice a diet containing black currant extract or black currant powder for one month, visual function was measured and analyzed qualitatively and quantitatively using precise OKR (optokinetic response).

[0023] (3) Measurement of spatiotemporal frequency sensitivity Visual stimuli were created using MATLAB / Psychtoolbox (Brainard DH. The Psychophysics Toolbox. Spatial Vision. 1997; 10: 433-36.) and presented on monitors placed around the mouse on three sides. Sinusoidal stripes were used as visual stimuli. The spatial and temporal frequency parameters of the sine wave stripe stimuli were varied to examine their spatiotemporal characteristics. Spatial frequency (SF) refers to the fineness of the stripes as they move, and temporal frequency (TF) refers to the speed at which the stripes move. The spatial frequency was varied over five levels: SF = 0.0313, 0.0625, 0.125, 0.25, and 0.5 cycles / degree, and the temporal frequency was varied over eight levels: TF = 0.1875, 0.375, 0.75, 1.5, 3, 6, 12, and 24 Hz. The stimulus conditions for each trial were randomly selected from 62 stimulus conditions (31 types × 2 directions) (see Figure 1(A)).

[0024] (4) Contrast sensitivity measurement Contrast sensitivity was examined by varying the contrast of the sinusoidal stripe stimuli. The contrast was varied over eight levels: 1, 2, 4, 8, 16, 32, 64, and 96%. The stimulus conditions for each trial were randomly selected from 16 stimulus conditions (8 types x 2 directions) (see Figure 1(B)).

[0025] (5) Experimental tasks At the beginning of each trial, a static stripe stimulus pattern was presented on the monitor. After the static pattern was presented for 333 ms, the pattern was moved either leftward or rightward for 30 s. After the pattern was moved, a solid gray screen was presented to mark the end of the trial. The next trial began 2 s after the end (see Figure 1(C)).

[0026] (6) Eye movement measurement Eye movements of the right eye of a mouse were measured while a moving visual stimulus was presented. Under ketamine anesthesia, the mouse was attached to the skull with a head holder using dental cement. To minimize mouse movement during the experiment, the head was fixed by screwing the head holder onto a stainless steel rod, and the body was also fixed in a small case. An infrared light was shone onto the mouse's right eye, and a hot mirror was placed 60 degrees (60°) 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 using an infrared-sensitive camera (CCD camera) (sampling rate: 200 Hz). Because the hot mirror reflects infrared light but transmits visible light, the mouse was able to view the visual stimulus displayed on a monitor behind the hot mirror.

[0027] (7) Data analysis Eye position data were obtained by analyzing images of the mouse's eye using software (GetEye). The position of the pupil center was calculated from images of the mouse's eye taken at regular intervals. Eye position (gaze direction) was calculated based on the pupil center position. Eye position calibration was performed as follows: A mouse eye 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's eye during the experiment, and the position of the pupil center on the image was recorded when rotated 2 degrees to the left and 10 degrees to the right. Based on this data, the correspondence between the position of the pupil center on the image and the mouse's eye position (gaze direction) was determined, and the mouse's eye position was calculated. The eye position data were then differentiated to calculate eye velocity. The average eye velocity was measured for 30 seconds after the onset of the stimulus for each trial, and this was used as the magnitude of the evoked eye movement response. Data analysis was performed using MATLAB (registered trademark) (MathWorks, MA).

[0028] 2.Results 2-1 Spatiotemporal frequency characteristics Figure 3 shows the magnitude of the average speed of the optokinetic response for each group, fitted with a Gaussian function. (A) is the control group, (B) is the black currant extract group, and (C) is the black currant powder group. The vertical axis represents temporal frequency (Hz), and the horizontal axis represents spatial frequency (cycles / deg). (D) shows a plot of the optimal spatiotemporal frequency for each mouse. No differences were observed in the spatiotemporal frequency characteristics between the control group and the groups of mice given black currant extract or black currant powder.

[0029] Figure 4 shows the results for each group: (A) optimal spatial frequency [cycle / deg], (B) optimal temporal frequency [Hz], (C) response strength [deg / s] (how much movement per second), (D) optimal speed [deg / s], and (E) gain. (A) is the ability to distinguish the fineness of a moving object, (B) is the ability to distinguish the speed of a moving object, (C) is the speed at which the eyes can track a moving object, (D) is the speed at which a moving object is easiest to distinguish, and (E) is the rate at which the eyes can track a moving object. No changes were observed in any of the parameters in either the black currant extract group or the black currant powder group.

[0030] 2-2 Contrast Sensitivity Figure 5 shows the results of examining contrast sensitivity. (A) is the control group, (B) is the blackcurrant extract group, and (C) is the blackcurrant powder group. The vertical axis represents eye velocity (deg / s) and the horizontal axis represents contrast (%). (D) shows the average for each mouse group. Mice fed a diet containing blackcurrant extract showed an increase in eye velocity at high contrast, and a stronger OKR than the control group. However, no difference was observed when the diet contained blackcurrant powder. These results indicate that blackcurrant extract is more effective than blackcurrant powder in improving moving object contrast discrimination ability.

[0031] Example 2: Effect of blackcurrant anthocyanins on visual function 1. Materials and Methods C57 / BL6J mice (21-month-old males, weighing 20-30 g) were used. Cassis anthocyanins, delphinidin-3-O-rutinoside (D3R, delphinidin 3-O-rutinoside, Tokiwa Phytochemical Research Institute Co., Ltd.) or cyanidin-3-O-rutinoside (C3R, cyanidin 3-O-rutinoside, Tokiwa Phytochemical Research Institute Co., Ltd.), were dissolved in water at a concentration of 10 mg / ml and orally administered at 10 mg / kg every other day for one month. Water was used as a control for comparison. D3R and C3R are anthocyanins found only in cassis. After one month of oral administration of cassis anthocyanins, the optokinetic response was measured using the same method as in Example 1.

[0032] (1) Experimental group Control group (n=5): Normal water was given for one month. D3R group (n=5): D3R (10 mg / ml) was given at 10 mg / kg every other day for 1 month. C3R group (n=5): C3R (10 mg / ml) was given at 10 mg / kg every other day for 1 month. After one month of oral administration of D3R or C3R, visual function was measured and analyzed qualitatively and quantitatively using precise OKR (optokinetic response).

[0033] 2.Results 2-1 Spatiotemporal frequency characteristics Figure 6 shows the magnitude of the average velocity of the optokinetic response after administration of D3R or C3R, fitted with a Gaussian function. (A) is the control group, (B) is the D3R group, and (C) is the C3R group. The vertical axis represents temporal frequency (Hz), and the horizontal axis represents spatial frequency (cycles / deg). (D) shows the optimal spatiotemporal frequency for each mouse. No changes in spatiotemporal frequency characteristics were observed in either D3R or C3R.

[0034] Figure 7 shows the results after administration of D3R or C3R for (A) optimal spatial frequency [cycle / deg], (B) optimal temporal frequency [Hz], (C) response strength [deg / s] (how much movement per second), (D) optimal speed [deg / s], and (E) gain. No changes were observed in any of the parameters in either the D3R or C3R groups.

[0035] 2-2 Contrast Sensitivity Figure 8 shows the results of examining contrast sensitivity. (A) is the control group, (B) is the D3R group, and (C) is the C3R group. The vertical axis represents eye velocity (deg / s), and the horizontal axis represents contrast (%). (D) shows the average for each mouse group. In mice orally administered D3R or C3R, an increase in eye velocity was observed at high contrast, and a stronger OKR was observed than in the control group. In particular, a stronger OKR was observed in the D3R group than in the control group.

[0036] Figure 9 shows the results of the contrast sensitivity shown in Examples 1 and 2. The vertical axis represents eye velocity (deg / s) and the horizontal axis represents contrast (%). In particular, it was shown that the response to contrast changes increased when mice were fed a diet containing black currant extract and when D3R was orally administered to the mice.

[0037] The present invention has demonstrated that feeding black currant extract to mice inhibits a decrease in eye velocity at high contrast. Furthermore, the present invention has demonstrated that orally administering D3R, an anthocyanin unique to black currant, to mice inhibits a decrease in eye velocity at high contrast. In other words, the present invention has demonstrated that the composition of the present invention, which contains black currant extract or black currant anthocyanin as an active ingredient, is useful for improving the ability to discriminate contrast between moving objects.

[0038] The present invention is not limited to the above-described embodiments and examples, and various modifications are possible within the scope of the claims. The technical scope of the present invention also includes embodiments obtained by appropriately combining the technical means disclosed in different embodiments. Furthermore, all academic literature and patent documents described in this specification are incorporated herein by reference.

Claims

1. A composition for improving dynamic visual acuity, containing blackcurrant anthocyanin as an active ingredient.

2. 2. The composition according to claim 1, wherein the black currant anthocyanin is at least one selected from the group consisting of delphinidin-3-O-rutinoside and cyanidin-3-O-rutinoside.

3. The composition according to claim 1 or 2, wherein the improvement in dynamic visual acuity is an improvement in dynamic contrast discrimination ability.

4. The composition according to claim 1 or 2, which is a food or drink.

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