JP2019043932A - Composition for improving asthenopia or improving lowering of eye focus adjustment power - Google Patents

Abstract

To provide a composition and an agent useful for improving asthenopia or improving lowering of eye focus adjustment power.SOLUTION: The present invention provides a composition containing a quercetin glycoside as an active ingredient. In the composition, the quercetin glycoside is α-glucosyl rutin, preferably, α-mono glucosyl rutin.SELECTED DRAWING: Figure 1

Description

  The present invention relates to a composition for improving eyestrain or for reducing eye focus adjustment power, an agent for improving eye fatigue, and an agent for reducing eye focus adjustment power.

  In recent years, in addition to the effects of daily sun light such as ultraviolet rays or oxygen etc., eyes are also caused by lifestyle changes such as driving a car, increasing VDT (Visual Display Terminals) work, using TVs and smartphones, and decreasing sleeping time. Eye-related problems such as mental fatigue are increasing.

  As a symptom of eye strain, there is a failure in focusing the eyes. The eye's focus adjustment plays an important role in seeing things normally with the eyes and is regulated by the ciliary muscle. Overtension such as cramps and tension in the ciliary muscle leads to a reduction in eye focus adjustment and eye fatigue, and if the eye focus adjustment does not work properly, it causes myopia and hyperopia, and QOL (Quality of life) is reduced. In addition, it is important to improve the decrease in eye focus adjustment power due to hypertonia of the ciliary muscle and to reduce the fatigue of the eyes in regulating biological functions.

  Therefore, it is effective in the improvement of eye strain and the improvement of the eye focus adjustment power reduction, and the goods by which improvement of QOL, such as food and medicine, is expected is desired.

  As an attempt to improve eye fatigue through daily food etc., Patent Document 1 discloses that fruits such as blueberries containing a large amount of anthocyanin are processed into a form such as easy-to-ingest jam etc. ing. Patent Document 2 discloses a composition for treating eyestrain, which contains a blueberry leaf-derived substance.

  In addition, as a composition to be taken in the form of medicines and foods, Patent Document 3 discloses a composition for improving ocular regulatory dysfunction comprising xanthophyll and a peptide. Further, Patent Document 4 discloses an eye fatigue improving agent containing crocetin or a pharmacologically acceptable salt thereof as an active ingredient.

JP 2001-224320 A JP, 2015-196673, A JP 2008-297222 A Japanese Patent Application Publication No. 2007-31426

  However, in the method described in Patent Document 1, it is difficult to increase the absolute amount of the active ingredient, and it is difficult to obtain an effect on symptoms such as eye strain. Moreover, the composition described in Patent Document 2 needs to be taken for a certain period of time before the effect is exhibited, and it is difficult to obtain the effect in a short time. Furthermore, the compositions or agents described in Patent Documents 3 and 4 have a problem that the effect in a short time is hardly obtained and the flavor is bad.

  Therefore, an object of the present invention is to provide a composition and an agent effective for the improvement of eyestrain and the improvement of the reduction in eye focus adjustment power.

  The present inventors have found that quercetin glycosides have an effect of improving eye fatigue and an effect of reducing eye focus adjustment power, and completed the present invention.

That is, the present invention provides the following inventions.
[1] A composition for improving eyestrain or for reducing eye focus adjustment power, which comprises quercetin glycoside as an active ingredient.
[2] The composition for improving eyestrain or for reducing eye focus adjustment power according to [1], wherein the quercetin glycoside is α-glucosylrutin.
[3] The composition for improving eyestrain, or for reducing eye focus adjustment power according to [2], wherein the α-glucosylrutin is α-monoglucosylrutin.
[4] An eyestrain improving agent containing quercetin glycoside as an active ingredient.
[5] An agent for improving eye focus adjustment ability which contains quercetin glycoside as an active ingredient.
[6] The eye strain improving agent according to [4], wherein the quercetin glycoside is α-glucosylrutin.
[7] The agent for improving eye focus adjustment ability according to [5], wherein the quercetin glycoside is α-glucosylrutin.
[8] The eye strain improving agent according to [6], wherein the α-glucosylrutin is α-monoglucosylrutin.
[9] The agent for improving eye focus adjustment power as described in [7], wherein the α-glucosylrutin is α-monoglucosylrutin.

  The composition or agent for improving conventional eye fatigue and eye focus adjustment reduction needs to be taken for a certain period of time before the effect is developed, but the composition and agent of the present invention can be administered in single doses and It can be effective in a short time. The composition and agent of the present invention have the effect of relaxing the ciliary muscle to promote the alleviation and alleviation of symptoms associated with ciliary muscle hypertonia, and have eye fatigue and eye focus adjustment ability The drop can be effectively improved.

FIG. 1 is a view showing that quercetin glycosides have the effect of improving eyestrain. FIG. 2 is a diagram showing that quercetin glycosides have the effect of improving the reduction in eye focus control. FIG. 3 is a view showing that quercetin glycosides have the effect of improving eyestrain. FIG. 4 is a diagram showing that quercetin glycosides have the effect of improving the reduction of eye focus control.

  The composition for improving eyestrain of the present invention or the composition for reducing eye focus adjustment power (hereinafter also abbreviated as the composition of the present invention) and the agent for improving eye fatigue and eye focus adjustment power of the invention (Hereafter also abbreviated as the agent of the present invention) contains quercetin glycoside as an active ingredient.

  In the present invention, "quercetin glycoside" refers to a glycoside of quercetin which is a kind of polyphenol, and is represented by the following formula (I).

  In formula (I), (X) n represents a sugar chain, and n is an integer of 1 or more.

  Here, as the sugar constituting the sugar chain represented by X which is bonded to quercetin by glycosidic bond, for example, glucose, rhamnose, galactose, glucuronic acid and the like can be mentioned, and glucose and rhamnose are particularly preferable. Further, n is not particularly limited as long as it is 1 or more, but is preferably 1 to 16, and more preferably 1 to 8. When n is 2 or more, the X moiety may be composed of one type of sugar chain, or may be composed of a plurality of sugar chains.

  The quercetin glycosides include those obtained by treating existing quercetin glycosides with an enzyme or the like and transglycosylating. Specific examples of quercetin glycosides include rutin, glucosylrutin, quercitrin and isoquercitrin.

  In one aspect of the present invention, one compound included in quercetin glycoside may be used alone, or a plurality of compounds may be mixed and used. The origin of quercetin glycosides is not particularly limited. For example, as a plant containing a large amount of quercetin or quercetin glycosides, buckwheat, enju, queper, apple, tea, onion, grape, broccoli, moth berry, raspberry, cowberry, cranberry , Opuntia, leafy vegetables, citrus fruits and the like.

  In addition, quercetin glycosides are extracts obtained by increasing the concentration of quercetin glycosides by concentration and operation of purified sugar, for example, using a concentrate or purified product of quercetin glycoside-containing extracts be able to. A conventionally known method can be used as the concentration method or purification method.

  In one aspect of the present invention, it is preferable to use α-glucosylrutin as a quercetin glycoside. α-glucosylrutin is a compound contained as a main component in a product known as “enzyme-treated rutin” (sometimes referred to as “glycotransfer rutin”) and is represented by the following formula (II) The compound having the following structure, that is, a compound in which one or more (about 2 to 20) glucoses are bound to a glucose residue in a rutinose residue possessed by rutin by α1 → 4 bond.

  In the present specification, among α-glucosylrutin, one in which only one glucose is bound is referred to as “α-monoglucosylrutin”, and one in which two or more glucose are bound is referred to as “α-polyglucosylrutin”.

  That is, in the following formula (II), α-glucosylrutin is generally a compound in which n is 1 to 20, α-monoglucosylrutin is a compound in which n is 1 and α-polyglucosylrutin is generally n is a compound of 2 to 20;

  Even in the case of α-monoglucosylrutin, the action and effect of the composition or agent of the present invention and the general action and effect on α-glucosylrutin are exhibited without problems, and the molecular weight of α-monoglucosylrutin is α-polyglucosyl Since the molecular weight of rutin is smaller than that of rutin, the number of molecules per unit mass is larger for α-monoglucosylrutin, which is considered to be advantageous in terms of effects. Therefore, it is preferable that a part or all of α-glucosylrutin be α-monoglucosylrutin.

  Enzymatically-treated rutin is a rutin in the presence of an α-glucosyl sugar compound (cyclodextrin, partially degraded starch, etc.), a rutin glycosyltransferase (cyclodextrin glucanotransferase (CGTase, EC2.4.1.19), etc.) Is a product (hereinafter also referred to as first enzyme-treated rutin) obtained by reacting an enzyme having the function of adding glucose to

  The first enzyme-treated rutin contains various α-glucosylrutins different in the number of bound glucose, ie, an aggregate consisting of α-monoglucosylrutin and other α-glucosylrutin, and rutin which is an unreacted substance Composition. If necessary, the first enzyme-treated rutin is purified using, for example, a porous synthetic adsorbent and a suitable eluate to remove sugar donors and other impurities and to further reduce the content of rutin, The first enzyme-treated rutin (a purified product of α-glucosylrutin) having an increased purity of α-glucosylrutin is obtained.

  Alternatively, the first enzyme-treated rutin is treated with an enzyme having a glucoamylase activity, such as glucoamylase (EC 3.2.1.3), which cleaves an alpha-1,4-glucosidic bond at a glucose unit, and a plurality of glucose are In the added α-glucosylrutin, the α-glucosyl rutin itself is α- by leaving only one glucose residue directly attached to the glucose residue (in the rutinose residue) and leaving the other glucose residue. An enzyme-treated rutin containing a large amount of monoglucosylrutin (hereinafter also abbreviated as a second enzyme-treated rutin) can be obtained. This enzyme treatment does not cleave the glucose residue in the rutinose residue directly linked to the quercetin backbone from the quercetin backbone.

  α-glucosylrutin is contained as a main component in, for example, trade name “αG rutin PS”, trade name “αG rutin P”, trade name “αG rutin H”, and the like manufactured by Toyo Seika Sho Co., Ltd. These goods are compositions containing 10 to 90% by weight of α-monoglucosylrutin.

  The composition comprises (i) preparing the above-described first enzyme-treated rutin, (ii) treating the first enzyme-treated rutin with an enzyme having glucoamylase activity, and almost all α-glucosylrutin as α-monoglucosyl It can be manufactured by the procedure of converting it into rutin.

  The content of quercetin glycoside which is an active ingredient in the composition or agent of the present invention is preferably 0.001% by mass or more, more preferably 0.02% by mass or more. The upper limit is not particularly limited, but usually 90% by mass or less is preferable.

  In addition, components, such as (alpha)-glucosyl rutin contained in the composition or agent of this invention can be confirmed by the chromatogram of HPLC, The content of each component or the purity of a specific component is the peak area of a chromatogram It can be calculated from

  In the case of oral intake (oral administration), the effective amount of quercetin glycoside which is an active ingredient in the composition or agent of the present invention depends on the condition and age of the subject, for example, 10 mg per day per adult. The above is preferable, more preferably 50 mg or more, further preferably 100 mg or more, particularly preferably 300 mg or more, and 2500 mg or less is preferable, more preferably 1000 mg or less, still more preferably 800 mg or less, particularly preferably 500 mg or less .

  Specifically, for example, when the active ingredient is α-monoglucosylrutin, the effective amount in the composition or agent of the present invention is preferably 7.5 mg or more per adult, more preferably 37.5 mg per adult. The amount is more preferably 75 mg or more, particularly preferably 225 mg or more, and preferably 1875 mg or less, more preferably 750 mg or less, still more preferably 600 mg or less, particularly preferably 375 mg or less.

  The amount described above may be taken (administered) once a day, or may be taken (administered) divided into multiple times a day. As used herein, "effective amount" means an amount that is significant to improve eye fatigue of a subject or to improve the reduction in eye focus adjustment. The said significant amount can be suitably set by those skilled in the art in consideration of the description of the example of this specification, etc.

  The agent of the present invention may be taken (administered) as it is as a supplement or the like, or at least one of an action to improve eye fatigue and an action to improve eye focus adjustment ability to be provided to a composition such as food and drink It may be used as an additive of In the composition of the present invention, quercetin glycoside which is an active ingredient can be blended as it is or in the form of an agent containing quercetin glycoside.

  A composition which can be formulated as an additive for adding the agent of the present invention to at least one of eye fatigue improvement action and eye focus adjustment reduction action and the composition of the present invention are particularly limited. For example, food and drink, and a pharmaceutical composition can be mentioned.

  In the present invention, food and drink are classified into cosmetic food / health food, functional indication food, food for specified health use, dietary supplement, food with indication for reduction of disease risk, food for sick people, etc. Is included. The disease risk reduction indication includes, for example, an indication that it is for improving, treating, alleviating and / or suppressing eye strain, improving, treating, alleviating and / or suppressing decrease in eye focus adjustment. The indication that it is a thing of

  Specific examples of the food and drink include, for example, supplements; carbohydrate-containing food and drink such as rice, fish, noodles, bread and pasta; Western confections such as cookies and cakes; , Gums, and various confectionery products such as frozen or frozen desserts such as jelly, yogurt and pudding; juices, soft drinks, milk drinks, tea drinks, jelly drinks, powder drinks, functional drinks, nutritional supplement drinks and non-alcohol beer Various beverages such as beer; alcoholic beverages such as beer and low-malt beer; liquid food and drink such as soup, miso soup and soup; processed products using eggs; processed products of seafood or livestock meat;

  Moreover, the food-drinks in this invention can contain other components, such as a nutritional supplement component other than the said active ingredient. Such components include, for example, vitamins, minerals, various plants and their extracts, purified products and fractions, microorganisms and their growth factors and microbial products, dietary fibers and their enzymatic degradation products, animals and their substances Extracts, purified products, degradation products and products, various oligosaccharides, lipids, various proteins and protein degradation products can be mentioned.

  The pharmaceutical composition of the present invention can be formulated using a pharmaceutically acceptable carrier according to a method commonly practiced in the art.

  The composition or agent of the present invention is not particularly limited as long as the desired effects of the present invention can be obtained. For example, routes such as oral (eg, buccal, sublingual, etc.), parenteral (eg, eye drops, intravenous, intramuscular, subcutaneous, transdermal, transnasal, transpulmonary, etc.) can be mentioned. Among these, a less invasive route is preferable, and oral is more preferable.

  One embodiment of the composition or agent of the present invention in the case of oral ingestion (oral administration) is, for example, solid embodiments such as powder, fine granules, granules, capsules, tablets, sachets, tablets, boluses, lozenges, etc .; And liquid embodiments such as extracts, suspensions, syrups, elixirs, emulsions, dispersions, etc .; and semi-liquid, cream, paste and the like.

  The composition or agent of the present invention may be taken in the form of a pill (powder or concentrate in a capsule) or after being put in or dissolved in a liquid such as water or hot water (similar to drinking powdered tea) It may be taken (administered) in the form of powder or granules (including freeze-dried granules).

  One embodiment of the composition or agent of the present invention for parenteral administration is, for example, an eye drop or composition such as an aqueous solution, a suspension, an emulsion, a liquid such as a dispersion, etc .; semi-liquid, creamy, paste Ophthalmic solution or composition such as aqueous solution, suspension, emulsion, dispersion liquid etc. drop solution or composition; aqueous solution, suspension, emulsion, dispersion liquid etc. intravenous injection or Composition, intramuscular injection or composition or subcutaneous injection or composition; transdermal administration agent or composition such as liquid such as aqueous solution, suspension, emulsion, dispersion, etc .; aqueous solution, suspension, emulsion, dispersion Intranasal administration or composition or transpulmonary administration or composition such as body fluid etc. powder, fine granules etc. Suppository or composition such as rectal suppository or composition or vaginal suppository or composition etc. Aspect, and the like.

  The composition or agent of the present invention may be added to quercetin glycosides, and any conventional auxiliary ingredient used for producing solid dosage forms or liquid dosage forms, such as excipients, diluents, buffers. One or more of agents, flavoring agents, coloring agents, flavoring agents, binders, surfactants, thickeners, lubricants, suspending agents, preservatives, antioxidants, etc. may be contained.

  The timing at which the composition or agent of the present invention is ingested (administered) is not particularly limited. However, since the composition or agent of the present invention has an immediate effect, eye fatigue and / or eye focus adjustment It is preferable to take (administer) when you feel a decrease in power. In addition, eye fatigue and / or reduction in eye focus adjustment are likely to occur after heavy use of the eyes, so it can be taken during dry eye and eye fatigue periods (eg evening) or before and after VDT work etc. Administration) is preferable.

  Hereinafter, the present invention will be described in detail based on examples, but the embodiments of the present invention are not limited to the examples.

Example 1
Adults who feel eye fatigue using a placebo-controlled double-blind comparative crossover method to evaluate the improvement effects of VDT work on eye strain and the improvement effects on reduction in eye focus control, as shown below Subjective index (visual evaluation scale, hereinafter abbreviated as VAS) and objective index (frequency of appearance of high-frequency component of adjustment fines movement distance, High Frequency Component 1, abbreviated as HFC1 below) and objective index were evaluated for 18 men and women .

The experimental schedule was as follows.
9 am to 9:20: Take a break with an eye mask without looking at the PC and listen to music for the last 5 minutes of the break.
・ 9:20 am: Conducted the first VAS questionnaire.
-9: 20 am-9:30 am: 1st HFC 1 measurement.
9:30 am: Take the sample.
9:30 am to 10 am: VDT load.
・ 10 am: Conducted the second VAS questionnaire.
10:00 am to 10:10 am: The second HFC1 measurement.
10:10 am-10:30 am: Take a break with an eye mask without looking at the PC, and listen to music for the last 5 minutes of the break.
-10:30 am-10:40 am: The 3rd HFC1 measurement.

  In the VDT work, a personal computer monitor was installed at a distance of 30 cm from the eye, and alphabetic typing work was performed for 30 minutes. As samples, prepare test food (quercetin glucoside-blended hard capsule containing 187.5 mg of α-monoglucosyl rutin) and control food (quercetin glucoside-free hard capsule) and prepare each capsule at 9:30 Grain intake. The contents of the hard capsule of the test food and the control food are shown in Table 1.

  The VAS questionnaire measured the length from the left end of the 10 cm line segment to the hatched position for the item "eye fatigue" as the answer value. As for the answer value, 10 is the best, 0 is the worst, and higher values mean the improvement. That is, with regard to the item of “eye fatigue”, “very tired” is the worst state, and “not feeling tired at all” is the best state. The results of evaluation by VAS are shown in FIG.

  Moreover, about HFC1 measurement, the value of HFC1 using the autoref keratometer ARK-560 (made by Nidek) and eye control function analysis software AA-2 (made by Nidek) was evaluated for the tension state of the ciliary muscle. The results are shown in FIG.

  As shown in FIG. 1, in the evaluation of subjective symptoms of eye fatigue by the VAS scale, the group receiving the control food showed no significant change, whereas the group receiving the test food received the control food The VAS scale was significantly improved after loading and after rest as compared to the group. From the results, it was shown that intake of quercetin glycoside improves and reduces eye strain.

  In addition, as shown in FIG. 2, in the evaluation of the eye's focus control power by HFC1 measurement, the group receiving the test food compared to the group receiving the control food, compared to the group receiving the control food The value decreased significantly. The results indicate that intake of quercetin glucoside relaxes the ciliary muscle and relieves the tense state, thereby improving the decrease in eye's focusing ability.

Example 2
A placebo controlled double blind comparative crossover method was used to evaluate VAS and HFC1 for 27 adult men and women who felt eye strain. Test samples (hard capsules containing quercetin glucoside containing 90 mg of α-monoglucosyl rutin) and control food (hard capsules containing no quercetin glycosides) were prepared as samples, and the experiment was conducted except that 3 capsules were consumed. Same as Example 1. The contents of the hard capsule are shown in Table 2.

  The VAS questionnaire measured the length from the left end of the 10 cm line segment to the hatched position for the item "eye fatigue" as the answer value. The answer values are 0 for the best, 10 for the worst, and lower for the improvement. That is, with regard to the item of “eye fatigue”, “very tired” is the worst state, and “not feeling tired at all” is the best state. The result evaluated by VAS is shown in FIG. Moreover, the result of having evaluated the value of HFC1 is shown in FIG.

  As shown in FIG. 3, in the evaluation of subjective symptoms of eye fatigue by the VAS scale, the group receiving the control food showed no significant change, whereas the group receiving the test food received the control food VAS scale was significantly reduced after loading compared to group. From this result, even when 360 mg of enzyme-treated rutin (containing 270 mg of quercetin glycoside) was taken (Example 2, FIG. 3), 500 mg of enzyme-treated rutin was taken (containing 375 mg of quercetin glycoside) Similar to the case (Example 1, FIG. 1), it was shown that eyestrain improves and reduces.

  In addition, significant changes were observed particularly in Example 1 where 375 mg of quercetin glycoside was ingested after rest (FIG. 1), and significant changes were observed particularly in Example 2 in which 270 mg of quercetin glycoside was ingested. The results also suggest that adjusting the intake of quercetin glycosides may adjust the timing to improve and reduce eyestrain.

  As shown in FIG. 4, in the evaluation of the eye's focus control power by HFC1 measurement, the group receiving the test food has a higher value of HFC1 before and after taking a break than after the control compared to the group receiving the control food. It dropped significantly. From this result, even when the intake amount of quercetin glycoside is 270 mg (Example 2, FIG. 4), the intake amount of quercetin glycoside is 375 mg similarly to (Example 1, FIG. 2). It has been shown that, by relaxing the ciliary muscle and relieving the tense state, the reduction in eye's focusing ability is improved.

  The composition or agent of the present invention has the effect of alleviating ciliary muscle hypertonia, and has the effect of improving the eye strain and improving the reduction of the eye's focusing ability. From this feature, the composition or agent of the present invention is used as a novel food and drink, pharmaceutical composition, etc. for improving, treating, alleviating and / or suppressing eye strain and / or eye focus deterioration. Are expected to

Claims (3)

  A composition for improving eyestrain or for reducing eye focus adjustment power, which comprises quercetin glycoside as an active ingredient.   The composition for improving eyestrain or for reducing eye focus adjustment power according to claim 1, wherein the quercetin glycoside is α-glucosylrutin.   The composition for improving eyestrain or for reducing eye focus adjustment power according to claim 2, wherein the α-glucosylrutin is α-monoglucosylrutin.

Images