Composition for improving ocular blood flow

Abstract

The purpose of the present invention is to provide a composition for improving a state associated with ocular blood flow by evaluating the action on the ocular blood flow. Also provided is a composition for improving and / or maintaining ocular blood flow, which contains ginger and / or a ginger extract. Also provided are: a composition for maintaining the soundness of vascular tissue of an eye, which contains the aforementioned component; an anti-aging composition for the eyes; the present invention provides a composition for improving and / or maintaining the appearance or enlargement of eye soundness, visual field stenosis, visual field loss, or dark spots, and provides a composition for treating and / or preventing ocular circulatory disorders.

Description

Technical Field

[0001] The present invention relates to a composition for improving ocular blood flow. Specifically, the present invention relates to a composition for improving and / or maintaining ocular blood flow; a composition for maintaining the health of ocular vascular tissue; an anti-aging composition for the eye; a composition for improving and / or maintaining the health of the eye, narrow visual field, visual field defect, or the appearance or expansion of dark spots; and a composition for treating and / or preventing ocular circulation disorders. Background Art

[0002] There are about 1,600 known species of plants in the Zingiberaceae family, and ginger (Zingiber officinale), ginger (Zingiber mioga), turmeric (Curcuma), etc. are used as spices and functional materials.

[0003] Ginger contains gingerol as a main component, and also contains shogaol, dehydrogingerdione, etc. Ginger is known to have various effects from these components, for example, it has been proposed to be used for improving indigestion, improving motion sickness, treating diabetes, analgesics, etc. (Patent Document 1). Prior art literature Patent Literature

[0004] Patent Document 1: Japanese Patent Application Publication No. 2005-511641. Summary of the invention Problems to be solved by the invention

[0005] However, there are not enough reports on the use of ginger in the eye field.

[0006] Therefore, an object of the present invention is to evaluate the effect of ginger on ocular blood flow when used in the eye area, and to provide a composition for improving the state related to ocular blood flow. Technical solutions to the problem

[0007] The present inventors have conducted intensive research to solve the above problems and have found that ginger and / or ginger extracts that are safely used in the food and pharmaceutical fields have an activity of improving and / or maintaining ocular blood flow, thereby completing the present invention.

[0008] That is, the present invention provides the following compositions.

[0009] [1] A composition for improving and / or maintaining ocular blood flow, characterized in that it contains ginger and / or a ginger extract.

[0010] [2] A composition for maintaining the health of ocular vascular tissue, characterized in that it contains ginger and / or a ginger extract.

[0011] [3] An anti-aging composition for eyes, characterized by containing ginger and / or ginger extract.

[0012] [4] A composition for improving and / or maintaining eye health, narrow visual field, visual field loss, or the appearance or expansion of scotoma, characterized in that it contains ginger and / or ginger extract.

[0013] [5] A composition for treating and / or preventing ocular circulatory disorders, characterized in that it contains ginger and / or a ginger extract.

[0014] [6] The composition as described in [5], characterized in that the ocular circulatory disorder is glaucoma, retinal vein occlusion, retinal artery occlusion, ocular ischemic syndrome, internal carotid artery occlusion, renal retinopathy, amaurosis fugax, and age-related macular degeneration.

[0015] [7] The composition according to any one of [1] to [6], which is a medicine, a drink or a food.

[0016] [8] The composition according to [7], characterized in that it is an orally disintegrating tablet, a chewable tablet, a maltose tablet, a granule, a powder, or a liquid.

[0017] [9] The composition according to any one of [1] to [8], wherein the ginger and / or ginger extract is red ginger and / or red ginger extract.

[0018]

[10] The composition as described in [1], characterized in that the ocular blood flow is retinal and / or choroidal blood flow. Advantageous Effects of the Invention

[0019] According to the present invention, ginger and / or ginger extracts that are safely used in the food and pharmaceutical fields can improve ocular blood flow and effectively improve related eye conditions. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] [ Figure 1 ] Figure 1 This is a graph showing the measurement results of the blood flow rate of the ocular blood vessels passing through the ginger preparation in Test Example 2. [ Figure 2 ] Figure 2 This is a photograph of the eye showing the results of the study of the ocular blood flow reduction model in Test Example 3. [ Figure 3 ] Figure 3This is a graph showing the results of the study on the ocular blood flow reduction model in Test Example 3. [ Figure 4 ] Figure 4 This is a photograph showing the eye after evaluating the effect of ginger administration 10 minutes after administration of endothelin-1 in Test Example 3. [ Figure 5 ] Figure 5 This is a graph showing the measurement results of the blood flow rate in the ocular blood vessels caused by the administration of ginger 10 minutes after the administration of endothelin-1 in Test Example 3. [ Figure 6 ] Figure 6 This is a graph showing the measurement results of the blood flow rate in the ocular blood vessels caused by the administration of ginger 10 minutes after the administration of endothelin-1 in Test Example 3. [ Figure 7 ] Figure 7 This is a graph showing the measurement results of the blood flow rate in the ocular blood vessels caused by the administration of ginger 10 minutes after the administration of endothelin-1 in Test Example 3. [ Figure 8 ] Figure 8 This is a photograph showing the eye after evaluating the effect of ginger administration 20 minutes after administration of endothelin-1 in Test Example 3. [ Fig. 9 ] Fig. 9 This is a graph showing the measurement results of the blood flow rate in the ocular blood vessels caused by the administration of ginger 20 minutes after the administration of endothelin-1 in Test Example 3. [ Fig.10 ] Fig.10 This is a graph showing the measurement results of the blood flow rate in the ocular blood vessels caused by the administration of ginger 20 minutes after the administration of endothelin-1 in Test Example 3. [ Fig.11 ] Fig.11 This is a graph showing the measurement results of the blood flow rate in the ocular blood vessels caused by the administration of ginger 20 minutes after the administration of endothelin-1 in Test Example 3. [ Fig.12 ] Fig.12 This is a graph showing the measurement results of the blood flow rate of the ocular blood vessels caused by the use of ginger after cold stress in Test Example 4. DETAILED DESCRIPTION

[0021] [Composition for improving and / or maintaining ocular blood flow] In one embodiment, the composition for improving and / or maintaining ocular blood flow of the present invention contains ginger and / or a ginger extract.

[0022] (Ginger and / or ginger extract) Ginger (Zingiber officinale) is a perennial herb belonging to the Zingiberaceae family. Ginger is known to have a warming effect on the body and has been consumed in countries around the world since ancient times. Ginger contains gingerol as a main component, and contains trace amounts of shogaol, dehydrogingerdione, etc. Furthermore, ginger further contains trace amounts of more than 50 volatile essential oil components and more than 200 irritating spicy components. These main components and trace components bring about various physiological activities and are being studied in the fields of lipid metabolism, arteriosclerosis, cancer, allergies, arthritis, etc.

[0023] The part of ginger is not particularly limited as long as the effects of the present invention are exhibited, but examples thereof include at least one selected from the group consisting of roots, stems, leaves, and flowers, preferably at least one selected from the group consisting of roots, stems, and leaves, more preferably at least one selected from the group consisting of roots and stems, and more preferably rhizomes.

[0024] In the present invention, the effects can be exerted by using ginger and / or ginger extracts. In one embodiment, when ginger extracts (ginger extracts) are used, the extraction method is not limited as long as the effects of the present invention are exerted.

[0025] In the present specification, the extract of ginger (ginger extract) can be a crude extract extracted from the whole plant or essential parts (flowers, flower heads, flower buds, flower buds, inflorescences, leaves, branches, branches and leaves, rhizomes, root barks, roots, barks, fruits, pericarps, beans, seeds, etc., preferably rhizomes) itself, or a product that has been further refined, concentrated, or obtained by synthesis, or a commercial product can be used. The method for obtaining the plant extract is not particularly limited, and a conventional extraction method, purification method, concentration method, synthesis method, drying and powdering method, etc. can be used.

[0026] As an example, the ginger extract is an extract obtained by extracting ginger or its crushed product by immersion extraction with water and / or an organic solvent and filtering the residue, and removing the solvent from the extract; or these fine powders; or the extract or the product obtained by dissolving, dispersing, or diluting the extract or the product removed from the solvent using an appropriate solvent, etc.; commercial products can also be used. As an example of other extraction methods, the ginger extract can also be extracted after processing such as steaming the rhizome of ginger. In addition, the periderm of the rhizome may be removed or used directly without removal.

[0027] In this specification, when using plant extracts (also called plant extracts), in more detail, water (including hot water), methanol, ethanol, isopropanol, ethylene glycol, 1,3-butanediol, glycerol and other alcohols, esters such as ethyl acetate; ketones such as acetone, methyl ethyl ketone, nitriles such as acetonitrile; ethers such as diethyl ether and tetrahydrofuran; pentane, hexane, cyclopentane, cyclohexane saturated hydrocarbons; aromatic hydrocarbons such as toluene; halogenated hydrocarbons such as dichloromethane and chloroform; other organic solvents such as dimethylformamide and dimethyl sulfoxide (all of which can be water-containing) are used as extraction solvents, and can also be one or two arbitrary mixed solutions. Among these solvents, water, ethanol, 1,3-butanediol, or these mixed solutions are preferred. The extracts recorded in this specification can be obtained from various raw material companies, and these extracts are usually sold in the form of excipients in most cases, but there is no limitation. In the following, the amount of extract refers to the dry solid content.

[0028] The extraction solvent of the ginger extract is not limited as long as the effects of the present invention are exhibited, but water, ethanol, or hydrous ethanol is preferred, and hydrous ethanol is more preferred.

[0029] Commercially available food materials containing ginger or ginger extracts include, for example, ginger extract powder (Matsuura Pharmaceutical Co., Ltd.), ginger extract NE (Ikeda Sugar Chemical Co., Ltd.), red ginger extract P (ORYZA Oil Chemical Co., Ltd.), Kintoki ginger powder (Xiangrong Industrial Co., Ltd.), etc., but are not limited to these commercially available products.

[0030] In addition, ginger is used as a raw drug for traditional Chinese medicine preparations and is classified as follows: raw ginger is fresh ginger, raw ginger dried directly is dried ginger, and dried ginger steamed and dried is dried ginger. The raw ginger in the raw drug is defined as the 18th revision of the Japanese Pharmacopoeia, and contains 0.3% or more of [6]-gingerol (C 17 H 26 O4: 294.39). Crude drugs with specifications stipulated in the Japanese Pharmacopoeia are commercially available, and such various crude drugs can also be used in the present invention.

[0031] Although not limited, red ginger (Zingiber officinale Rubra.) can be used as ginger. Red ginger has a stronger spiciness than common white ginger and is also used as a spice, traditional medicine, and the like.

[0032] Examples of food ingredients containing red ginger or commercially available products of red ginger extracts include red fragrant ginger powder (Ryusendo), Hokka Hokka red ginger powder (MK Laboratories), red ginger extract P, red ginger extract-WSP, red ginger extract-PC, red ginger extract-WSPC, red ginger extract-LC (all from ORYZA Petrochemical Co., Ltd.), but are not limited to these commercially available products.

[0033] Although not limited, as a red ginger extract, the content of [6]-gingerol and [6]-shogaol is preferably 3.0% by mass or more, and more preferably 6.0% by mass or more. In addition, the content of tannin is preferably 0.5% by mass or more, and more preferably 1.5% by mass or more, in terms of proanthocyanidin B2. In addition, although not limited, as an excipient, the content of cyclodextrin is preferably 10% to 90%, more preferably 30% to 70% by mass, and further preferably 33% to 67% by mass.

[0034] From the viewpoint of significantly exerting the effects of the present invention, when the ginger extract is used, its content relative to the total amount of the composition may be, for example, 0.01% by mass or more, 0.05% by mass or more, 0.1% by mass or more, 0.3% by mass or more, 0.5% by mass or more, 1% by mass or more, 3% by mass or more, 5% by mass or more, 10% by mass or more, 20% by mass or more, or 90% by mass or less, 50% by mass or less, 25% by mass or less, 10% by mass or less, 5% by mass or less, 3% by mass or less, or 1% by mass or less. The content of the ginger extract is preferably 0.01% by mass to 95% by mass, more preferably 0.05% by mass to 70% by mass, further preferably 0.1% by mass to 50% by mass, and particularly preferably 0.5% by mass to 30% by mass.

[0035] From the viewpoint of significantly exerting the effect of the present invention, when ginger is used, its content relative to the total amount of the composition may be, for example, 0.1% by mass or more, 0.5% by mass or more, 1% by mass or more, 3% by mass or more, 5% by mass or more, 10% by mass or more, 30% by mass or more, 50% by mass or more, or 99% by mass or less, 95% by mass or less, 90% by mass or less, 80% by mass or less, 70% by mass or less, or 60% by mass or less. The content of ginger is preferably 0.1% by mass to 99% by mass, more preferably 0.5% by mass to 95% by mass, further preferably 1% by mass to 90% by mass, and particularly preferably 3% by mass to 80% by mass.

[0036] When ginger extract is used, the raw drug ratio is not limited, but examples thereof include 1 to 100:1, 10 to 80:1, preferably 20 to 60:1, and more preferably 30 to 45:1 (for example, 1 kg of extract can be extracted from 30 kg to 45 kg of ginger rhizomes).

[0037] [use] The composition for improving and / or maintaining ocular blood flow of the present invention is also suitably used to improve conditions, symptoms, and diseases related to ocular blood flow. In the examples (test examples) described later, it was confirmed that when healthy rats and ocular blood flow reduction model rats were orally ingested with the composition of the present invention, ocular blood flow increased. In addition, in the test examples, it was confirmed that other systemic conditions and ocular conditions (pulse, mean blood pressure, intraocular pressure, etc.) of the rats were not affected.

[0038] By using the composition of the present invention, the blood flow of the eye can be increased, and the blood flow of the eye can be suppressed from decreasing or maintained. Thus, since the blood flow of the eye can be increased, in one embodiment, the present invention can also be used to maintain and enhance the soundness of the vascular tissue of the eye. In the vascular tissue of the eye, in the optic nerve head, the ophthalmic artery enters the optic nerve and is used as the central retinal artery or the posterior ciliary artery to deliver the blood that provides nutrition to the retina. In addition, at the back of the eyeball, the ophthalmic artery branches into a short posterior ciliary artery and arrives at the choroidal artery after receiving the blood flow in the optic nerve head, delivering the blood that provides nutrition to the outer layer of the retina.

[0039] In the eye, there are parts richly covered with the vascular network, and parts without vascular invasion necessary to ensure the visual field. For example, since the macula with the fovea is formed without vascular invasion, it is infiltrated with nutrients from the surrounding retinal blood vessels. Therefore, in one embodiment, the present invention contributes to the anti-aging of the entire eye including the eye tissue without vascular invasion by increasing the blood flow to the vascular tissue of the eye, and can improve and / or maintain the soundness. In addition, in one embodiment, in the case of narrow visual field, visual field defect, and scotoma caused by ischemic part of the blood, abnormal function of vascular tissue of the eye, etc., the present invention can improve these conditions by increasing the blood flow to the vascular tissue of the eye, and can inhibit the occurrence or expansion of these symptoms (inhibit the progress).

[0040] The present invention is to increase the blood flow of the vascular tissue of the eye, and can actively deliver blood components to each eye tissue including the eye tissue without vascular invasion. If the blood component infiltration from the blood vessel is increased, the circulation of tissue fluid is also improved (improvement of tissue blood flow). In recent years, in addition to the importance of improving eye blood flow, the importance of improving the circulation of tissue fluid (tissue blood flow) has also been pointed out. In this specification, this idea is referred to as the improvement of the overall blood flow of the eye. In the embodiments described later (test examples), it is confirmed that when the composition of the present invention is taken orally by healthy rats and eye blood flow reduction model rats, in addition to improving the blood flow of major blood vessels such as the central retinal artery that looks radial from the optic nerve papilla, the circulation of capillaries and tissue fluid (tissue blood flow) is also improved, and the improvement of the overall blood flow of the eye is confirmed.

[0041] In recent years, in the field of eye research, there are reports that glaucoma is not only related to the blood flow of ocular blood vessels, but also to the overall blood flow of the eye, including the blood flow of ocular tissues. Specifically, it is reported that in glaucoma patients, all items of ocular blood flow, ocular tissue blood flow, and overall ocular blood flow are lower than those of healthy people (Chao Gu. Ailing Li. Ling Yu, Diagnostic performance of laser speckle flowgraphy in glaucoma: a systematic review and meta-analysis, Int Ophthalmol (2021) 41: 3877-3888). Thus, in one embodiment, since the present invention can increase ocular blood flow, ocular tissue blood flow, and overall ocular blood flow, it can be used for the treatment and / or prevention of ocular circulatory disorders.

[0042] Examples of such ocular circulatory disorders include glaucoma, retinal vein occlusion, retinal artery occlusion, ocular ischemic syndrome, internal carotid artery occlusion, renal retinopathy, amaurosis fugax, or age-related macular degeneration. Although not limited, from the perspective of increasing ocular blood flow, ocular tissue blood flow, and overall ocular blood flow, more suitable ocular circulatory disorders are glaucoma, age-related macular degeneration, or retinal vein occlusion.

[0043] In one embodiment, since it has been confirmed that the present invention increases the blood flow of the vascular tissue of the eye, it can also be suitably used, for example, for: people who want to improve the blood circulation of the eye; people who are concerned about the blood circulation of the eye; people who want to improve the function of the optic nerve or the muscles around the eye by improving the blood circulation of the eye; people who are concerned about the function of the optic nerve or the muscles around the eye; people who want to send blood to the eye by improving the blood circulation of the eye; people who want to support the health of the eye; people who are concerned about the visual field defect; people who are concerned about the narrowing of the visual field; people who have difficulty seeing clearly. In addition, in one embodiment, the present invention can also be enclosed in a package that makes these states and uses clear or associated in the form of words, sentences, and illustrations before being distributed to consumers.

[0044] As described above, the eye is covered with fine blood vessels, and the microcirculation (microcirculation) is responsible for the nutrition of each tissue. Therefore, in one embodiment, the present invention can also be suitably used for people who want to improve the microcirculation of the eye or people who are concerned about the microcirculation of the eye.

[0045] In this specification, the term "prevention" means preventing or delaying the occurrence of a specific condition or disease, or reducing the risk of the occurrence of a specific condition or disease.

[0046] In the present specification, improvement means to alleviate or improve a specific condition or disease; to prevent or delay the deterioration of an abnormal condition; or to prevent, delay, or reverse a specific condition or disease.

[0047] The composition of the present invention can also be used by adding to food, beverages, pharmaceuticals, feed, pet food or mixing with these. Alternatively, it can be used directly as a beverage or food. Alternatively, it can be used as a beverage or food that explicitly or implicitly indicates the functional properties of improving ocular blood flow, protecting the retina, anti-aging of the eye, maintaining the integrity of the eye, improving the pattern of vision, maintaining the homeostasis of vascular tissue, reducing or preventing the risk of ocular circulatory disorders, that is, it can be used as a health food, a functional labeled food, a food for patients, and a food for specific health care. In addition, even if the functionality is not explicitly or implicitly indicated, it can be used as a so-called doctor's supplement provided by a doctor in a hospital and / or clinic.

[0048] Health foods, functional labeled foods, foods for patients, and foods for specific health care, specifically, can be used as various preparations such as solid preparations (tablets, orally disintegrating tablets, granules, fine granules, powders, capsules, chewable tablets, maltose, etc.), liquids (syrups, suspensions), and liquid foods. Foods in preparation form can be manufactured in the same manner as known pharmaceutical preparations, by mixing active ingredients and carriers that are acceptable as foods (for example, appropriate excipients, etc.), and then using conventional means to manufacture. Although there is no limitation to the preparation form, orally disintegrating tablets, chewable tablets, maltose, granules, powders, or liquids are preferred from the viewpoint of significantly exerting the effects of the present invention.

[0049] For example, tablets can be prepared by mixing powdered active ingredients and pharmaceutically acceptable carrier components (excipients, etc.) and compressing them, and confectionery tablets such as candies (malt sugar) can be prepared by injecting them into a mold. Tablets can also be coated with sugar to make them into sugar-coated tablets. Tablets can be single-layer tablets or layered tablets such as double-layer tablets.

[0050] Powdered granules such as granules can also be prepared by various granulation methods (extrusion granulation, pulverization granulation, dry compression granulation, fluidized bed granulation, tumbling granulation, high-speed stirring granulation, etc.), and tablets can be prepared by appropriately combining the above granulation methods, tableting methods (wet tableting, direct tableting), etc.

[0051] Capsules can be prepared by filling powders and granules (powders, granules, etc.) into capsules (soft or hard capsules) by conventional methods.

[0052] Liquid preparations can be prepared by dissolving or dispersing each component in an aqueous medium (purified water, purified water containing ethanol, etc.) as a carrier component, filtering or sterilizing as necessary, and filling in a predetermined container and sterilizing. The preferred dosage form of the solid preparation of the present invention is a capsule or a tablet, and a soft capsule (soft capsule, soft capsule) is more preferred.

[0053] Soft capsules have a smooth surface and are easy to take, so they are popular with users. As general methods for producing soft capsules, there are: a flat plate method, a rotary method, and a seamless method.

[0054] In the rotary method (punching method), the sheet-like capsule film is sandwiched with the flowing filling content and is formed into a capsule shape along the holes of a rotating cylindrical die. On the other hand, in the seamless method (dripping method), the capsule film composition and the content are synchronously ejected from multiple concentric nozzles to form a seamless capsule shape.

[0055] The base of the film of the soft capsule is not particularly limited, but can be starch, pullulan, cellulose, polyvinyl alcohol, gelatin, succinic gelatin, etc., preferably starch, gelatin, succinic gelatin, more preferably gelatin, succinic gelatin. These bases can be used alone or in combination of two or more.

[0056] In addition, the composition of the present invention can be manufactured as: liquid beverages such as soups, juices, fruit juice drinks, milk, milk drinks, whey drinks, lactic acid bacteria drinks, tea drinks, alcoholic beverages, coffee drinks, carbonated beverages, refreshing drinks, water drinks, cocoa drinks, jelly drinks, sports drinks, and diet drinks; semi-solid foods such as puddings and yogurts; noodles, desserts, spreads, etc.

[0057] When preparing the composition of the present invention as a food composition, various food additives may also be formulated. Examples of food additives include antioxidants, pigments, spices, seasonings, sweeteners, acidulants, pH adjusters, quality stabilizers, preservatives, and the like.

[0058] When the composition of the present invention is prepared as a pharmaceutical composition, it is prepared as a preparation containing ginger and / or ginger extract as an active ingredient and preferably a pharmaceutically acceptable carrier. A pharmaceutically acceptable carrier generally refers to an inert, non-toxic, solid or liquid bulking agent, diluent or encapsulation material that does not react with the active ingredient, for example, water, ethanol, polyols, appropriate mixtures thereof, solvents such as vegetable oils, or dispersion media, etc.

[0059] The pharmaceutical composition is administered orally or non-orally, for example, into the oral cavity, the digestive tract, or the nasal cavity. Examples of oral preparations include: solid preparations (tablets, orally disintegrating tablets, granules, fine granules, powders, capsules, chewable tablets, maltose, etc.); liquid preparations (syrups, suspensions, inhalants), etc. Examples of non-oral preparations include: eye drops, drops, nasal drops, and injections, etc. Although there is no limitation on the form of the preparation, orally disintegrating tablets, chewable tablets, maltose, granules, powders, or liquid preparations are preferred from the viewpoint of significantly exerting the effects of the present invention.

[0060] The pharmaceutical composition may further include additives commonly used in the pharmaceutical field. Such additives include, for example, excipients, binders, disintegrants, lubricants, antioxidants, colorants, flavoring agents, etc., which may be used appropriately as necessary. In order to achieve a slow release based on the purpose of long-term action, it may also be coated with known retardants, etc. The pharmaceutical composition may further include other additives and medicaments (e.g., antacids, gastric mucosal protective agents) as necessary.

[0061] The pharmaceutical composition can be applied in the form of an oral composition, an internal composition, etc. In addition, the pharmaceutical composition can be used for therapeutic purposes or non-therapeutic purposes.

[0062] The daily oral intake or dosage of ginger and / or ginger extract for adults can be appropriately determined based on the individual's condition, body weight, sex, age, activity of the material, route of intake or administration, intake or administration schedule, formulation form or other factors. The daily oral intake or dosage of ginger and / or ginger extract for adults is, for example, preferably 0.01 mg / kg body weight / day or more, more preferably 0.02 mg / kg body weight / day or more, more preferably 0.05 mg / kg body weight / day or more, and particularly preferably 0.1 mg / kg body weight / day or more. The daily oral intake or dosage of ginger and / or ginger extract for adults is, for example, preferably 10 mg / kg body weight / day or less, more preferably 5 mg / kg body weight / day or less, more preferably 2 mg / kg body weight / day or less, and particularly preferably 1 mg / kg body weight / day or less. The daily oral intake or dosage of ginger and / or ginger extract for adults is, for example, preferably 0.01 mg / kg body weight / day to 10 mg / kg body weight / day, more preferably 0.02 mg / kg body weight / day to 5 mg / kg body weight / day, more preferably 0.05 mg / kg body weight / day to 2 mg / kg body weight / day, and particularly preferably 0.1 mg / kg body weight / day to 1 mg / kg body weight / day. The content of ginger and / or ginger extract can be set to an amount that becomes the intake or dosage.

[0063] In one embodiment, the daily oral intake or dosage of the ginger extract for an adult is, for example, preferably 0.5 mg / day or more, more preferably 1 mg / day or more, more preferably 3 mg / day or more, particularly preferably 5 mg / day or more, and most preferably 10 mg / day or more. The daily oral intake or dosage of the ginger extract for an adult is, for example, preferably 500 mg / day or less, more preferably 200 mg / day or less, more preferably 100 mg / day or less, and particularly preferably 50 mg / day or less. The daily oral intake or dosage of the ginger extract for an adult is, for example, preferably 0.5 to 500 mg / day or less, more preferably 1 to 200 mg / day or less, more preferably 3 to 100 mg / day or less, and particularly preferably 5 to 50 mg / day or less.

[0064] In addition, in one embodiment, the daily oral intake or dose of ginger for an adult is, for example, preferably 20 mg / day or more, more preferably 40 mg / day or more, more preferably 120 mg / day or more, particularly preferably 200 mg / day or more, and most preferably 400 mg / day or more. The daily oral intake or dose of ginger for an adult is, for example, preferably 5000 mg / day or less, more preferably 3000 mg / day or less, more preferably 1000 mg / day or less, and particularly preferably 800 mg / day or less. The oral intake or dose of ginger is, for example, preferably 20 to 5000 mg / day or less, more preferably 40 to 3000 mg / day or less, more preferably 120 to 1000 mg / day or less, and particularly preferably 200 to 800 mg / day or less.

[0065] When converting the dose for animals to the dose for humans, there is no limitation, but for example, the following method can be adopted: the effective dose for animals is converted into the dose for humans as the dose per kg of body weight, and the dose is set to 1 / 60 or less. That is, if the effective dose for animals is X mg / kg, the dose for humans (mg / day) can be calculated as X (mg) × body weight (kg) / 60 to 600, etc. In one embodiment, the daily oral intake or dosage of ginger and / or ginger extract for adults can be, for example, 1 mg / day or more, 2 mg / day or more, 3 mg / day or more, 4 mg / day or more, 5 mg / day or more, 6 mg / day or more, 7 mg / day or more, 8 mg / day or more, 9 mg / day or more, or 10 mg / day or less, or 1000 mg / day or less, or 900 mg / day or less, or 800 mg / day or less, or 700 mg / day or less, or 600 mg / day or less, or 500 mg / day or less, or 400 mg / day or less, or 300 mg / day or less, or 200 mg / day or less, or 150 mg / day or less, or 100 mg / day or less, or 75 mg / day or less, or 50 mg / day or less, or 30 mg / day or less, or 20 mg / day or less, or 10 mg / day or less.

[0066] In addition, the daily oral intake or dosage form for adults, for example, in the case of capsules, can be divided into 1 capsule to 6 capsules, 1 capsule to 4 capsules, 1 capsule to 3 capsules, or 1 capsule to 2 capsules for taking.

[0067] The composition of the present invention can be taken or administered once to several times a day, usually once to 6 times a day, once to 3 times a day, once to 2 times a day, or at any period and interval, but once a day is preferred.

[0068] The present invention can also be implemented as follows. A composition for improving and / or maintaining ocular blood flow, comprising ginger and / or ginger extract; a composition for maintaining the health of ocular vascular tissue, comprising ginger and / or ginger extract; an anti-aging composition for the eye, comprising ginger and / or ginger extract; a composition for improving and / or maintaining the health of the eye, narrow visual field, visual field defect, or the appearance or expansion of dark spots, comprising ginger and / or ginger extract; a composition for treating and / or preventing ocular circulatory disorders, comprising ginger and / or ginger extract; a composition comprising ginger and / or ginger extract for improving and / or maintaining ocular blood flow; a composition comprising ginger and / or ginger extract A composition containing ginger and / or ginger extract for maintaining the health of the vascular tissue of the eye; a composition containing ginger and / or ginger extract for anti-aging of the eye; a composition containing ginger and / or ginger extract for improving and / or maintaining the health of the eye, narrow visual field, visual field defect, or the appearance or expansion of dark spots; a composition containing ginger and / or ginger extract for treating and / or preventing ocular circulatory disorders; a use of ginger and / or ginger extract for manufacturing an agent for improving and / or maintaining ocular blood flow; a use of ginger and / or ginger extract for manufacturing an agent for maintaining the health of the vascular tissue of the eye; a use of ginger and / or ginger extract for Preparation of an anti-aging agent for the eye; use of ginger and / or ginger extracts for preparing an agent for improving and / or maintaining the health of the eye, narrow visual field, visual field loss, or the appearance or expansion of dark spots; use of ginger and / or ginger extracts for preparing a therapeutic and / or preventive agent for ocular circulatory disorders; a method for improving and / or maintaining ocular blood flow, comprising allowing a person to ingest a composition containing ginger and / or ginger extracts; a method for maintaining the health of vascular tissue of the eye, comprising allowing a person to ingest a composition containing ginger and / or ginger extracts; an anti-aging method for the eye, comprising allowing a person to ingest a composition containing ginger and / or ginger extracts; a method for improving and / or maintaining the health of the eye A method for treating and / or preventing ocular circulatory disorders, comprising allowing a person to ingest a composition containing ginger and / or a ginger extract; a method for treating and / or preventing ocular circulatory disorders, comprising allowing a person to ingest a composition containing ginger and / or a ginger extract; a composition, use, or method as described, wherein the ocular circulatory disorder is glaucoma, retinal vein occlusion, retinal artery occlusion, ocular ischemic syndrome, internal carotid artery occlusion, renal retinopathy, amaurosis fugax, age-related macular degeneration; a composition as described, which is a pharmaceutical product or a drink or food; a composition, use, or method as described, wherein the dosage form is an orally disintegrating tablet, a chewable tablet, a maltose tablet, a granule, a powder, or a liquid;The composition, use, or method, wherein the ginger is red ginger; the composition, use, or method, wherein the ginger and / or ginger extract is red ginger and / or red ginger extract; the composition, use, or method, wherein the ginger part includes rhizomes; the composition, use, or method, wherein the extracting solvent in the ginger extract is aqueous ethanol; the composition, use, or method, wherein the total content of [6]-gingerol and [6]-shogaol in red ginger is 3.0% by mass or more; the composition, use, or method, wherein the total content of [6]-gingerol and [6]-shogaol in red ginger is 6.0% by mass or more. % or more; as described in the composition, use, or method, wherein the content of tannin in red ginger is 0.5% by mass or more calculated as proanthocyanidin B2; as described in the composition, use, or method, wherein the content of tannin in red ginger is 1.5% by mass or more calculated as proanthocyanidin B2; as described in the composition, use, or method, wherein the content of ginger extract is 0.01% by mass to 95% by mass; as described in the composition, use, or method, wherein the content of ginger extract is 0.05% by mass to 70% by mass; as described in the composition, use, or method, wherein the content of ginger extract is 0.1% by mass to 50% by mass; as described in the composition, use, or method, wherein the content of ginger extract is 0.5% by mass to 3 0 mass %; as described in the composition, use, or method, wherein the content of ginger is 0.1 mass % to 99 mass %; as described in the composition, use, or method, wherein the content of ginger is 0.5 mass % to 95 mass %; as described in the composition, use, or method, wherein the content of ginger is 1 mass % to 90 mass %; as described in the composition, use, or method, wherein the content of ginger is 3 mass % to 80 mass %; as described in the composition, use, or method, wherein the daily oral intake of ginger and / or ginger extract is 0.5 mg to 500 mg; as described in the composition, use, or method, wherein the daily oral intake of ginger and / or ginger extract is 1 mg to 20 0mg; as described in the composition, use, or method, wherein the daily oral intake of ginger and / or ginger extract is 3mg to 100mg; as described in the composition, use, or method, wherein the daily oral intake of ginger and / or ginger extract is 5mg to 50mg; as described in the composition, use, or method, wherein the daily oral intake of ginger is 20mg to 5000mg; as described in the composition, use, or method, wherein the daily oral intake of ginger is 40mg to 3000mg; as described in the composition, use, or method, wherein the daily oral intake of ginger is 120mg to 1000mg;As described in the composition, use, or method, wherein the daily oral intake of ginger is 200 mg to 800 mg; As described in the composition, use, or method, wherein the ocular blood flow is the blood flow of the retina and / or choroid; As described in the composition, use, or method, wherein the ocular blood flow includes the blood flow of ocular tissues. ; [Example]

[0069] Next, the present invention will be specifically described with reference to Examples, but the present invention is not limited to the following Examples. In addition, the amount of the extract shown in the Examples is shown as an amount including dry solid conversion and excipients, etc., unless otherwise specified.

[0070] [Test Example 1. Ocular blood flow evaluation test in human retinal capillary endothelial cells] The activation of nitric oxide (NO) synthase, which causes vasodilation, was evaluated when ginger was added to human retinal capillary endothelial cells. HRMEC (human retinal capillary endothelial cells) were cultured at 3×10 5 Cells were seeded at 1000 × 100 cells / mL on a 6-well plate, and 0.001% of red ginger extract (red ginger extract-P, manufactured by ORYZA Oil Chemical Co., Ltd., labeled as "O-2" in the figure, the same below) diluted with 0.5% dimethyl sulfoxide (DMSO) was added and incubated at 37°C for 30 minutes. 25 μg / lane of the protein solution derived from the cells was separated by SDS-PAGE using 7.5% acrylamide gel, and after blocking with 1% skim milk adjusted with Tw-PBS, 1000-fold diluted anti-P-eNOS antibody (Ser1177, Cell Signaling Technology, Inc. #9715) and 5000-fold diluted anti-eNOS antibody (total, Cell Signaling Technology, Inc. #32037) were added, and incubated at room temperature for one hour, and then incubated at room temperature for one hour with 5000-fold diluted goat anti-rabbit IgG-HRP (Sigma, #A0545). Then, the signal of Gel dog (Bio-Rad Laboratories, Inc.) was detected by luminescence with ECL prime. P-eNOS / e-NOS was calculated and compared with the case where no red ginger extract was added as 1.

[0071] [Table 1] Ginger Extract Concentration 0% (0.5% DMSO) 0.001％ P-eNOS / e-NOS 1.00 1.63

[0072] The results are shown in Table 1. It was confirmed that the addition of ginger extract to human retinal capillary endothelial cells activated the nitric oxide (NO) synthesizing enzyme that dilates blood vessels (increase in P-eNOS / e-NOS value), suggesting that ginger is effective in improving blood flow in the posterior ocular region.

[0073] [Test Example 2: Ocular blood flow evaluation test in normal rats] In order to evaluate the effect of an oral (sublingual) agent on ocular blood flow, changes in blood flow around the optic nerve head of the eye were measured using healthy rats. The ocular blood flow as a baseline in healthy rats (Brown Norway, male, 8-12 weeks old, manufactured by SLC, weighing about 200 g, the same below) was measured using laser speckle blood flow imaging (LSFG-NAVI, manufactured by Sandian Technology Co., Ltd.) and the accompanying analysis application (LSFG analyzer). According to this measurement method, ocular blood flow can be measured and analyzed in real time in a non-invasive or low-invasive manner without using mydriatic agents or contrast agents.

[0074] One week after the baseline ocular blood flow was measured, 25 mg or 50 mg of red ginger extract powder (red ginger extract-P, manufactured by ORYZA Oil Chemical Co., Ltd., marked as "O-2" in the figure, the same below) as a test sample was sublingually administered, and anesthesia was administered 10 minutes later. 30 minutes later, the MBR value, which is an indicator of ocular blood flow, was measured again by laser speckle blood flow imaging. The measurement results of the ocular blood flow that became the baseline and the ocular blood flow after taking the test sample are shown in Figure 1 . In each dosage group, 8 rats were used and statistical processing was performed by Holm-Sidak test. In addition, AveALL(V) in the figure represents the blood flow rate in the vascular area (MBR average value, the same applies below).

[0075] like Figure 1 As shown, when ginger (red ginger extract) was administered, an increase in ocular blood flow was observed in healthy rats. It was also confirmed that the effect of increasing ocular blood flow increased depending on the amount of ginger intake.

[0076] [Test Example 3: Ocular blood flow evaluation test in rats with reduced ocular blood flow] (3-1. Review of the ocular blood flow reduction model) Healthy rats (Brown Norway, male, 8-12 weeks old, manufactured by SLC) were anesthetized and endothelin-1 (labeled as "ET1" in the figure, the same below) was injected intravitreally 10 minutes later at various doses of no dose (control group), 1.25 pmol, 2.5 pmol, or 5.0 pmol. After 20 minutes, the ocular blood flow (AveALL(A): blood flow in the entire area) was measured by laser speckle blood flow imaging. The blood flow map of the posterior ocular region in each measurement result is shown in Figure 1. Figure 2 , and the analyzed graph is represented in Figure 3 The data were statistically processed using the Turkey-Kramer test.

[0077] like Figure 2 and Figure 3 As shown, it was confirmed that the ocular blood flow (blood flow in the whole area) was reduced by the administration of endothelin-1 (ET-1). It was confirmed that the ocular blood flow was significantly reduced in the group in which 2.5 pmol of endothelin-1 was administered intravitreally compared with the control group. Therefore, in the following test example, as an ocular blood flow reduction model, an ocular blood flow reduction model was established by administering 2.5 pmol of endothelin-1 intravitreally.

[0078] (3-2. Ocular blood flow evaluation test in rats with reduced ocular blood flow) (Oral administration group of the test sample) Healthy rats (Brown Norway, male, 8-12 weeks old, manufactured by SLC) were sublingually administered 50 mg of red ginger extract powder, anesthetized 10 minutes later, and 2.5 pmol of endothelin-1 was administered intravitreally 10 minutes later. Ocular blood flow (AveALL (A): blood flow in the entire area, AveALL (V): blood flow in the vascular area, AveALL (T): blood flow in the tissue area), pulse, mean blood pressure, and intraocular pressure were measured by laser speckle blood flow imaging 10 minutes and 20 minutes after the administration of endothelin-1.

[0079] (Control Group) The same procedure as the oral administration group was performed except that the red ginger extract powder was not administered. That is, healthy rats (Brown Norway, male, 8-12 weeks old, manufactured by SLC) were anesthetized and 10 minutes later, 2.5 pmol of endothelin-1 was administered intravitreally. Ocular blood flow (AveALL(A): blood flow in the entire area, AveALL(V): blood flow in the vascular area, AveALL(T): blood flow in the tissue area), pulse, mean blood pressure, and intraocular pressure were measured by laser speckle blood flow imaging 10 minutes and 20 minutes after the administration of endothelin-1.

[0080] The ocular blood flow map after 10 minutes from the administration of endothelin-1 is shown in Figure 4 , and the analyzed graph is shown in Figures 5 to 7 The data were statistically processed using the student-t test. In addition, the ocular blood flow map after 20 minutes from the administration of endothelin-1 is shown in Figure 8 , and the analyzed graph is shown in Figures 9 to 11 The data were statistically processed using the student-t test.

[0081] like Figures 4 to 11 As shown, in the group taking ginger (red ginger extract powder), an increase in ocular blood flow was confirmed even in the ocular blood flow reduction model rats compared to the control group. The increase in ocular blood flow was confirmed not only in the blood flow in the vascular area (AveALL(V)), but also in the blood flow in the tissue area (AveALL(T)) and the blood flow in the entire area (AveALL(A)).

[0082] Although the results are not shown, no significant differences were found between the two groups regarding pulse, mean blood pressure, and intraocular pressure 10 minutes and 20 minutes after the administration of endothelin-1. Therefore, it was confirmed that ginger (red ginger extract) is a component that can be safely ingested (administered) without affecting other systemic conditions or eye conditions, depending on its use.

[0083] Due to the use of endothelin-1 (ET1) the blood flow to the eye (blood flow to the whole area) is reduced. Figure 2 as well as Figure 3 ), so the state of loss of the soundness of the vascular tissue of the eye, the state of eye aging, and the state of ocular circulatory disorders are modeled. Therefore, it is suggested that the intake (dosage) of ginger is effective for improving and / or maintaining ocular blood flow, maintaining the soundness of the vascular tissue of the eye, anti-aging of the eye, narrow visual field, visual field defect, or dark spots, and the treatment and / or prevention of various ocular circulatory disorders. In addition, although not limited, the dosage of endothelin-1 (ET1) is used to model glaucoma with reduced ocular blood flow. Therefore, although not limited, it is suggested that the intake (dosage) of ginger is suitably used for the treatment and / or prevention of glaucoma in ocular circulatory disorders.

[0084] [Test Example 4: Ocular blood flow evaluation test after cold stress in human body] When a cold load is applied to a living body, vasoconstriction occurs to suppress heat dissipation from the skin blood vessels, thereby reducing blood flow. After the cold load, blood flow recovers over time. These phenomena are believed to occur in the same way as eye blood flow in a human body that is highly sensitive to cold loads. As in Test Examples 2 and 3, by using laser speckle blood flow imaging, changes in ocular blood flow can be quantitatively evaluated. If a substance can shorten the blood flow recovery period after a cold load, it can be expected to contribute to the improvement and / or maintenance of ocular blood flow, and be effective in maintaining the health of the vascular tissue of the eye, anti-aging of the eye, narrow visual field, visual field defect, or dark spots, and the treatment and / or prevention of various ocular circulatory disorders. Below, a cross-comparison test was used to evaluate the effect of red ginger extract on ocular blood flow after a cold load.

[0085] A nutritional supplement containing red ginger extract (red ginger extract-P, manufactured by ORYZA Oil Chemical Co., Ltd.) was used as a test food.

[0086] Healthy subjects were allowed to enter the test room and sit in a chair in the test room at a room temperature of 24°C to 25°C. After being allowed to stand still for 30 minutes and adapt to the test environment, they were allowed to sit in a chair in the test room at a room temperature of 24°C to 25°C for 30 minutes with or without taking the test food. Then, the ocular blood flow before the stress was measured using laser speckle blood flow imaging (LSFG-NAVI, manufactured by Sandian Technology Co., Ltd.) and the attached analysis application (LSFGanalyzer) in the same manner as in Test Examples 2 and 3 to obtain the blood flow value (initial value) before the cold stress.

[0087] Then, 30 minutes before the cold load, the subjects were asked to sit on a chair in a test room at 24°C to 25°C and wait quietly for 30 minutes, either taking or not taking the test food. The content of the red ginger extract itself (excluding excipients) in the test food was about 10 mg / day as a dry solid content.

[0088] After the initial value is measured, the nitrile glove is placed on the right hand, and the right hand below the neck is immersed in 40°C warm water for two minutes. Then, the right hand below the neck is immersed in 4°C cold water for one minute to perform cold stress. After the cold stress, the water is wiped off with a paper towel as soon as possible, and the fundus blood flow is measured 4 minutes and 6 minutes after the cold stress. The same test is performed on the same subject under crossover conditions, with a sufficient washout period.

[0089] The fundus blood flow measurement in this test example is to measure the blood flow (MBR average value) of the tissue area of ​​the optic nerve head. In addition, in the fundus blood flow measurement after consuming the target food and 4 minutes after the cold load, the subjects whose temperature of the optic nerve head decreased were evaluated as responders (9 in this test). The results are shown in Fig.12 The upper line graph is the test food group, and the lower line graph is the non-intake group. Fig.12 In FIG. 1 , the vertical axis represents the average value of the change in MBR.

[0090] like Fig.12 As shown, it was confirmed that the group taking ginger (red ginger extract) increased the blood flow to the eye after cold stress and shortened the blood flow recovery period compared to the control group. Therefore, it is expected that ginger (red ginger extract) contributes to the improvement and / or maintenance of blood flow to the eye, and is effective for maintaining the health of the vascular tissue of the eye, anti-aging of the eye, narrow visual field, visual field defect, or scotoma, and the treatment and / or prevention of various ocular circulatory disorders.

[0091] The red ginger extract used in the examples (red ginger extract-P, manufactured by ORYZA Oil Chemical Co., Ltd.) is a preparation extracted from rhizomes with aqueous ethanol, wherein the total content of [6]-gingerol and [6]-shogaol is 6.0% by mass or more, contains 1.5% by mass or more of tannin, and is mixed with an equal amount of cyclodextrin as an excipient.

Claims

1. A composition for improving and / or maintaining ocular blood flow, characterized in that: Contains ginger and / or ginger extract.

2. A composition for maintaining the health of ocular vascular tissue, characterized in that: Contains ginger and / or ginger extract.

3. An anti-aging composition for eyes, characterized in that: Contains ginger and / or ginger extract.

4. A composition for improving and / or maintaining the health of the eye, narrow visual field, visual field loss, or the appearance or expansion of scotoma, characterized in that: Contains ginger and / or ginger extract.

5. A composition for treating and / or preventing ocular circulatory disorders, characterized in that: Contains ginger and / or ginger extract.

6. The composition according to claim 5, characterized in that: Ocular circulatory disorders include glaucoma, retinal vein occlusion, retinal artery occlusion, ocular ischemic syndrome, internal carotid artery occlusion, renal retinopathy, amaurosis fugax, and age-related macular degeneration.

7. The composition according to claim 1, characterized in that: For medicines, drinks and food.

8. The composition according to claim 7, characterized in that: It is in the form of orally disintegrating tablets, chewable tablets, maltose, granules, powders or liquids.

9. The composition according to claim 1, characterized in that: The ginger and / or ginger extract is red ginger and / or red ginger extract.

10. The composition according to claim 1, characterized in that: Ocular blood flow refers to the blood flow of the retina and / or choroid.

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