Agent for suppressing reduction of palpebral fissure width

Abstract

To provide an excellent eyelid aperture width lowering inhibitor capable of suppressing an eyelid aperture width lowering in order to improve impression made on others and beauty.SOLUTION: Because a combination of amla and neem shows excellent eyelid aperture width lowering inhibitory action, this combination is usable for food product, quasi drug, and medicine having the eyelid aperture width lowering inhibitory action. Further, because a combination of amla, neem, and bilberry shows extremely excellent eyelid aperture width lowering inhibitory action, this combination is usable for food product, quasi drug, and medicine having the eyelid aperture width lowering inhibitory action.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to an agent for inhibiting a decrease in palpebral fissure width, which is characterized by containing amla and neem. More specifically, the present invention relates to an agent for inhibiting a decrease in palpebral fissure width, which is characterized by containing amla, neem, and bilberry. [Background technology]

[0002] As the old saying goes, "The eyes speak louder than words," and the eyes easily reflect one's health and mood, playing an important role in the impression one makes on others. In particular, palpebral fissure width (the distance from the edge of the upper eyelid to the edge of the lower eyelid, i.e., the maximum vertical width of the eye when open) (Non-Patent Document 1) significantly influences the impression one makes on others. However, it is easily affected by eye fatigue, poor vision, dry eyes, fatigue, drowsiness, and other factors, and palpebral fissure width tends to decrease, especially in the evening. This can make a person appear tired or gloomy, negatively impacting the impression one makes. Furthermore, as numerous makeup techniques have been proposed to make eyes appear larger, many people consider large, open eyes to be one of the elements of beauty (Non-Patent Document 2). Therefore, preventing a decrease in palpebral fissure width is desirable to improve the impression one makes on others and one's beauty.

[0003] Amla, scientifically known as Phyllanthus emblica, is also known as amalaki, emblica, malacca, or emblica. It grows on mountain slopes at altitudes of 1,500 meters or more in India, Southeast Asia, Taiwan, and southern China. It is one of the three major fruits in Indian Ayurvedic medicine, and in India, not only the fruit but also the seeds, leaves, trunk, and roots are all used as medicine. It is known to be effective against peptic ulcers and indigestion, as well as for its lipid-lowering and anti-arteriosclerotic effects (Non-Patent Document 3).

[0004] Neem, whose scientific name is Melia azadirachta, is also known as neem. It grows wild from Southeast Asia to the Middle East and has been revered since ancient times as a mystical tree. It is considered an essential mystical medicine in Indian Ayurveda. Pests dislike the bitter components contained throughout the tree, so it is used as an insect repellent. It is also known to exhibit nerve growth factor inhibitory activity (Patent Document 1), cyclooxygenase activity inhibitory activity (Patent Document 2), anti-inflammatory activity, and anti-itching activity (Patent Document 3).

[0005] The scientific name for bilberry is Vaccinium myrtillus, a wild blueberry species that grows in Northern Europe. Standardized bilberry extract, which has specifications for 15 types of anthocyanins, is included in the European Pharmacopoeia, and has long been used in Europe as a medicine for ophthalmological disorders, vascular disorders, and dermatitis. Its virus-inactivating effects (Patent Document 4), blood flow improvement effects, capillary protection effects, antitumor effects, and antiulcer effects (Non-Patent Document 4) have been revealed.

[0006] However, an agent for inhibiting a decrease in palpebral fissure width that is characterized by containing amla and neem, an agent for inhibiting a decrease in palpebral fissure width that is characterized by containing amla, neem, and bilberry, and a food composition containing them are completely unknown. [Prior art documents] [Patent documents]

[0007] [Patent Document 1] Japanese Patent Application Laid-Open No. 2016-190823 [Patent Document 2] Japanese Patent Application Laid-Open No. 2006-076910 [Patent Document 3] Japanese Patent Application Publication No. 6-199675 [Patent Document 4] Japanese Patent Application Publication No. 2018-197205 [Non-patent literature]

[0008] [Non-Patent Document 1] Cosmetology Research Report Vol.27 185-188(2019) [Non-patent document 2] Saitama Women's Junior College Research Bulletin Vol.20 71-91(2009) [Non-patent document 3] Pharmacia Vol.45 No.10 1015-1016(2009) [Non-patent document 4] Gifu Pharmaceutical University Bulletin Vol.65 20-27(2016) Summary of the Invention [Problem to be solved by the invention]

[0009] In view of the above-mentioned circumstances, an object of the present invention is to provide an excellent agent for inhibiting a decrease in palpebral fissure width. [Means for solving the problem]

[0010] As a result of intensive research aimed at solving the above-mentioned problems, the present inventors have found that a combination of amla and neem has an excellent effect of inhibiting the decrease in the width of the palpebral fissure.Furthermore, they have found that a combination of amla, neem, and bilberry has an extremely excellent effect of inhibiting the decrease in the width of the palpebral fissure.

[0011] The amla used in the present invention may be amla (Phyllanthus emblica), a plant of the Phyllanthaceae family. The part of amla used in the present invention is not particularly limited, but may include the fruit, seeds, wood, roots, leaves, etc., and it is preferable to use the fruit.

[0012] The neem used in the present invention may be neem (Melia azadirachta), a plant of the Meliaceae family. The part of the neem used in the present invention is not particularly limited, but examples include leaves, fruits, seeds, and bark, and it is preferable to use leaves.

[0013] The bilberry used in the present invention may be Vaccinium myrtillus, a plant of the Ericaceae family. The part of the bilberry used in the present invention is not particularly limited, but may include the fruit and leaves, and it is preferable to use the fruit.

[0014] The amla, neem, and bilberry used in the present invention can be used as is, or can be dried, crushed, shredded, or otherwise treated as necessary. Furthermore, amla, neem, and bilberry can be used as is, or can be used as an enzyme-treated product obtained by enzymatically treating amla, neem, or bilberry after the above treatment. Examples of enzymes used in the enzyme treatment include pectinase, xylase, protease, cellulase, and hemicellulase. These enzymes may be used alone or in combination. The amla used in the present invention is preferably treated with an enzyme, with pectinase treatment being particularly preferred.

[0015] The amla, neem, and bilberry used in the present invention can be extracted either directly or after drying, crushing, shredding, or other processing. Examples of solvents used for extraction include water, lower alcohols (methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, etc.), liquid polyhydric alcohols (1,3-butylene glycol, propylene glycol, glycerin, etc.), ketones (acetone, methyl ethyl ketone, etc.), acetonitrile, esters (ethyl acetate, butyl acetate, etc.), hydrocarbons (hexane, heptane, petroleum ether, etc.), and ethers (ethyl ether, tetrahydrofuran, propyl ether, etc.). These solvents may be used alone or in combination. Neem used in the present invention is preferably extracted with a polar solvent such as water or a lower alcohol, with water extraction being particularly preferred. Bilberry used in the present invention is preferably extracted with a polar solvent such as water or a lower alcohol, with hydroethanol extraction being particularly preferred.

[0016] The enzyme-treated product or extract may be used as is, or may be used after treatment such as concentration, dilution, filtration, decolorization with activated carbon or the like, deodorization, ethanol precipitation, etc. Furthermore, the extracted solution may be subjected to treatment such as concentration to dryness, spray drying, or freeze drying, and used as a dried product.

[0017] The intake amounts of amla, neem, and bilberry used in the present invention can be adjusted appropriately depending on the dosage form, purpose of use, age, body weight, etc. The daily intake amount of amla for adults is 0.01 to 500 mg, preferably 0.1 to 100 mg, of an enzyme-treated amla fruit product, which can be orally taken once to several times per day. The daily intake amount of neem for adults is 0.01 to 500 mg, preferably 0.1 to 100 mg, of a hot water extract of neem leaves, which can be orally taken once to several times per day. The daily intake amount of bilberry for adults is 0.1 to 1000 mg, preferably 10 to 500 mg, of a hydroethanolic extract of bilberry fruit, which can be orally taken once to several times per day. Amounts less than the above intake range may be sufficient, while amounts exceeding the range may be necessary. Furthermore, the method of adding the active ingredients in the formulation may be selected appropriately based on workability, either by adding them in advance or during production.

[0018] The agent for inhibiting a decrease in palpebral fissure width of the present invention can be used as a food, quasi-drug, or pharmaceutical. As a food, it can be used in the form of soft capsules, hard capsules, granules, tablets, gummies, beverages, jellies, etc. As a quasi-drug or pharmaceutical, it can be used in the form of oral capsules, powders, granules, tablets, sugar-coated tablets, syrups, pills, suspensions, liquids, emulsions, etc., or parenteral eye drops, injections, suppositories, topical skin preparations, etc. To achieve the objectives of the present invention, oral intake of a food or oral preparation is preferred.

[0019] The agent for inhibiting decrease in palpebral fissure width of the present invention may contain, as needed, ingredients used in ordinary foods, quasi-drugs, or pharmaceuticals, such as excipients, stabilizers, preservatives, binders, disintegrants, hydrocarbons, fatty acids, alcohols, esters, pH adjusters, antiseptics, and flavorings, within limits that do not impair the effects. Furthermore, the agent may contain ingredients such as plant materials, polyphenols, vitamins, sugars, and proteins, and preferably contains marigold pigments (containing lutein and zeaxanthin), astaxanthin, DHA, and the like, in order to achieve the objects of the present invention. [Effects of the Invention]

[0020] The agent for inhibiting a decrease in palpebral fissure width, which is characterized by containing neem and amla, according to the present invention, has an excellent effect of inhibiting a decrease in palpebral fissure width.Furthermore, the agent for inhibiting a decrease in palpebral fissure width, which is characterized by containing amla, neem, and bilberry, has an extremely excellent effect of inhibiting a decrease in palpebral fissure width. DETAILED DESCRIPTION OF THE INVENTION

[0021] The following examples are given for illustrative purposes only, and the scope of the present invention is not limited to these examples. The percentages in the contents shown in the examples represent percentages by weight. [Example]

[0022] Production Example 1: Enzyme-treated amla fruit 40 g of pectinase was added to 100 g of amla fruit and treated with stirring at 50°C for 4 hours. The filtrate was then concentrated and spray-dried to obtain 10.2 g of enzyme-treated amla fruit.

[0023] Production Example 2 Amla fruit hot water extract 2 L of purified water was added to 100 g of amla fruit, and the mixture was extracted at 95-100°C for 2 hours. The filtrate was then concentrated and freeze-dried to obtain 8.4 g of amla fruit hot water extract.

[0024] Preparation Example 3: Amla fruit 30% ethanol extract 1.4 L of purified water and 0.6 L of ethanol were added to 100 g of amla fruit, and the mixture was extracted at room temperature for 5 days. The filtrate was then concentrated to dryness to obtain 4.8 g of a 30% ethanol extract of amla fruit.

[0025] Production Example 4 Neem leaf hot water extract 2 L of purified water was added to 100 g of neem leaves, and the mixture was extracted at 95-100°C for 2 hours. The filtrate was then concentrated and freeze-dried to obtain 8.5 g of a hot water extract of neem leaves.

[0026] Preparation Example 5 Neem leaf 30% ethanol extract 1.4 L of purified water and 0.6 L of ethanol were added to 100 g of neem leaves, and the mixture was extracted at room temperature for 5 days. The filtrate was then concentrated to dryness to obtain 2.6 g of a 30% ethanol extract of neem leaves.

[0027] Production Example 6 Bilberry fruit 30% ethanol extract 1.4 L of purified water and 0.6 L of ethanol were added to 100 g of bilberry fruit, and the mixture was extracted at room temperature for 5 days. The filtrate was then concentrated to dryness to obtain 3.0 g of a 30% ethanol extract of bilberry fruit.

[0028] Production Example 7 Bilberry fruit 50% ethanol extract 100 g of bilberry fruit was added with 1 L of purified water and 1 L of ethanol, and the mixture was extracted at room temperature for 5 days. The filtrate was then concentrated to dryness to obtain 2.1 g of a 50% ethanol extract of bilberry fruit.

[0029] Next, examples of formulations using amla, neem, and bilberry according to the present invention will be given, but the present invention is not limited to these. [Example]

[0030] Formulation example 1: Soft capsule <Prescription> Component Content (%) 1. Amla fruit enzyme-treated product (Production Example 1) 0.5 2. Neem leaf hot water extract (Production Example 4) 0.5 3. Add linseed oil so that the total amount becomes 100 4. Beeswax 5.0 5. Glycerin fatty acid ester 5.0 6. Vitamin E 3.0 <Manufacturing method> Components 1 to 6 were mixed, and 250 mg of the mixture was filled into a coating composed of starch, carrageenan, reduced starch syrup, and glycerin. After drying, soft capsules were obtained. <Usage> Take 3 tablets per day.

[0031] Prescription example 2: Soft capsules <Prescription> Component Content (%) 1. Amla fruit enzyme-treated product (Production Example 1) 0.5 2. Neem leaf hot water extract (Production Example 4) 0.5 3. Bilberry 30% ethanol extract (Production Example 6) 16.0 4. Add linseed oil so that the total amount becomes 100 5. Beeswax 5.0 6. Glycerin fatty acid ester 5.0 7. Vitamin E 3.0 <Manufacturing method> Components 1 to 7 were mixed, and 250 mg of the mixture was filled into a coating composed of starch, carrageenan, reduced starch syrup, and glycerin. After drying, soft capsules were obtained. <Usage> Take 3 tablets per day.

[0032] Formulation example 3: Soft capsules <Prescription> Component Content (%) 1. Amla fruit enzyme-treated product (Production Example 1) 10.0 2. Neem leaf hot water extract (Production Example 4) 10.0 3. Bilberry 30% ethanol extract (Production Example 6) 17.0 4. Marigold pigment (containing lutein and zeaxanthin) 7.0 5. Add linseed oil so that the total amount becomes 100 6. Beeswax 5.0 7. Glycerin fatty acid ester 5.0 8. Vitamin E 3.0 <Manufacturing method> Components 1 to 8 were mixed, and 250 mg of the mixture was filled into a coating composed of starch, carrageenan, reduced starch syrup, and glycerin. After drying, soft capsules were obtained. <Usage> Take 3 tablets per day.

[0033] Prescription Example 4: Tablets <Prescription> Component Content (%) 1. Amla fruit hot water extract (Production Example 2) 0.01 2. Neem leaf 30% ethanol extract (Production Example 5) 0.01 3. Bilberry fruit 50% ethanol extract (Production Example 7) 0.3 4. Erythritol 60.4 5. Add maltitol so that the total amount is 100 6. Citric Acid 5.0 7. Sucrose fatty acid ester 3.0 8.Fragrance 0.1 <Manufacturing method> Ingredients 1 to 6 were mixed, and 10% water was added as a binder, followed by fluidized bed granulation. Ingredients 7 and 8 were added to the formed granules, mixed, and compressed to obtain tablets weighing 2 g each. <Usage> Take 3 tablets per day.

[0034] Comparative Example 1: Conventional soft capsule containing bilberry In the soft capsule formulation of Formulation Example 2, the enzyme-treated amla (Production Example 1) and hot water extract of neem leaves (Production Example 4) were replaced with linseed oil to produce conventional soft capsule formulations containing bilberry.

[0035] Comparative Example 2: Conventional soft capsule Conventional soft capsules were prepared by replacing the enzyme-treated amla (Production Example 1) and hot water extract of neem leaves (Production Example 4) in the soft capsules of Formulation Example 1 with linseed oil. [Example]

[0036] Test Example 1: Inhibitory effect on the decrease in palpebral fissure width when taken by humans Forty men and women (aged 25-65) who experienced difficulty opening their eyes in the evening were divided into four groups of 10 each. Test Group 1 received soft capsules containing amla and neem (Formulation Example 1), Test Group 2 received soft capsules containing amla, neem, and bilberry (Formulation Example 2), Test Group 3 received conventional soft capsules containing bilberry (Comparative Example 1), and Test Group 4 received conventional soft capsules (Comparative Example 2). Each group received three soft capsules per day, and facial images were taken in the morning and evening before and after three months of ingestion. Image analysis of the facial images was performed to measure the maximum vertical distance (the point where the eyes were widest vertically) from the edge of the upper eyelid to the edge of the lower eyelid to determine the palpebral fissure width. Furthermore, the difference between the evening palpebral fissure width and the morning palpebral fissure width was calculated to calculate the change in palpebral fissure width between morning and evening.

[0037] The results of Test Example 1 are shown in Table 1. Test Groups 1, 2, and 3 showed an increase in the amount of change in palpebral fissure width after 3 months of ingestion compared to before ingestion. In particular, Test Group 2 showed a significant increase in the amount of change in palpebral fissure width after 3 months of ingestion. Therefore, amla and neem were found to have an excellent inhibitory effect on the decrease in palpebral fissure width. Furthermore, the combination of amla, neem, and bilberry was found to have an extremely excellent inhibitory effect on the decrease in palpebral fissure width.

[0038] [Table 1] [Industrial Applicability]

[0039] As described above, the present invention can be used as an agent for inhibiting a decrease in palpebral fissure width containing amla and neem, an agent for inhibiting a decrease in palpebral fissure width containing amla, neem, and bilberry, and can also be used in foods, quasi-drugs, and pharmaceuticals containing these.

Claims

1. An agent for inhibiting the decrease in palpebral fissure width, characterized by containing an enzyme-treated amla fruit product obtained by treating amla fruit with pectinase and a hot water extract of neem leaves.

2. 2. The agent for suppressing a decrease in palpebral fissure width according to claim 1, characterized in that it contains a hydroethanolic extract of bilberry fruit.

3. A food composition for inhibiting a decrease in palpebral fissure width, comprising the agent for inhibiting a decrease in palpebral fissure width according to claim 1 or 2.

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