WO2024019171A1 - Composition for improving ocular blood flow - Google Patents

Composition for improving ocular blood flow Download PDF

Info

Publication number
WO2024019171A1
WO2024019171A1 PCT/JP2023/026874 JP2023026874W WO2024019171A1 WO 2024019171 A1 WO2024019171 A1 WO 2024019171A1 JP 2023026874 W JP2023026874 W JP 2023026874W WO 2024019171 A1 WO2024019171 A1 WO 2024019171A1
Authority
WO
WIPO (PCT)
Prior art keywords
ginger
blood flow
extract
ocular
composition
Prior art date
Application number
PCT/JP2023/026874
Other languages
French (fr)
Japanese (ja)
Inventor
徹 中澤
孝太 佐藤
美和子 蔀
寿枝 上田
恒星 塚本
Original Assignee
ロート製薬株式会社
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by ロート製薬株式会社 filed Critical ロート製薬株式会社
Publication of WO2024019171A1 publication Critical patent/WO2024019171A1/en

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L2/00—Non-alcoholic beverages; Dry compositions or concentrates therefor; Their preparation
    • A23L2/52—Adding ingredients
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/906—Zingiberaceae (Ginger family)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A61P27/06—Antiglaucoma agents or miotics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Definitions

  • the present invention relates to a composition for improving ocular blood flow.
  • compositions for improving and/or maintaining ocular blood flow compositions for maintaining the health of vascular tissue in the eye, anti-aging compositions for the eye, health of the eye, visual field narrowing, visual field defects. , or compositions for improving and/or maintaining the appearance or expansion of scotoma, and compositions for treating and/or preventing ocular circulation disorders.
  • Ginger contains gingerol as a main component, and also contains shogaol, dehydrogingerdione, etc. Ginger is known to have various effects due to these components, and its use has been proposed for improving indigestion, motion sickness, diabetes treatment, analgesic, etc. (Patent Document 1).
  • the present invention aims to evaluate the effect on ocular blood flow when ginger is used in the eye region, and to provide a composition that improves conditions related to ocular blood flow.
  • the present inventors conducted intensive studies and found that ginger and/or its extracts, which are safely used in the food and pharmaceutical fields, are effective in improving and/or maintaining ocular blood flow.
  • the present inventors have discovered that the compound has activity, etc., and have completed the present invention.
  • the present invention provides the following compositions.
  • a composition for improving and/or maintaining ocular blood flow containing ginger and/or an extract thereof.
  • a composition for maintaining the health of vascular tissue in the eye containing ginger and/or an extract thereof.
  • a composition for treating and/or preventing ocular circulation disorders containing ginger and/or an extract thereof.
  • the ocular circulation disorder is glaucoma, retinal vein occlusion, retinal artery occlusion, ocular ischemic syndrome, internal carotid artery occlusion, renal retinopathy, transient amaurosis, or age-related macular degeneration [5 The composition described in ].
  • composition according to [8] which is an orally disintegrating tablet, a chewable tablet, a candy, a granule, a powder, or a liquid.
  • Ginger and/or its extract is red ginger and/or its extract, The composition according to any one of [1] to [8].
  • composition according to [1] wherein the ocular blood flow is retinal and/or choroidal blood flow.
  • FIG. 1 is a graph showing the measurement results of blood flow in ocular blood vessels due to ginger administration in Test Example 2.
  • FIG. 2 is a photograph of the posterior segment of the eye showing the results of an examination of the ocular blood flow reduction type model in Test Example 3.
  • FIG. 3 is a graph showing the study results of the ocular blood flow reduction type model in Test Example 3.
  • FIG. 4 is a photograph of the posterior segment of the eye 10 minutes after endothelin-1 administration in Test Example 3, in which the influence of ginger administration was evaluated.
  • FIG. 5 is a graph showing the measurement results of blood flow in ocular blood vessels due to ginger administration 10 minutes after endothelin-1 administration in Test Example 3.
  • FIG. 1 is a graph showing the measurement results of blood flow in ocular blood vessels due to ginger administration in Test Example 2.
  • FIG. 2 is a photograph of the posterior segment of the eye showing the results of an examination of the ocular blood flow reduction type model in Test Example 3.
  • FIG. 3 is a graph showing the study results of the o
  • FIG. 6 is a graph showing the measurement results of blood flow in ocular blood vessels due to ginger administration 10 minutes after endothelin-1 administration in Test Example 3.
  • FIG. 7 is a graph showing the measurement results of blood flow in ocular blood vessels due to ginger administration 10 minutes after endothelin-1 administration in Test Example 3.
  • FIG. 8 is a photograph of the posterior segment of the eye 20 minutes after endothelin-1 administration in Test Example 3, in which the influence of ginger administration was evaluated.
  • FIG. 9 is a graph showing the measurement results of blood flow in ocular blood vessels due to ginger administration 20 minutes after endothelin-1 administration in Test Example 3.
  • FIG. 10 is a graph showing the measurement results of blood flow in ocular blood vessels due to ginger administration 20 minutes after endothelin-1 administration in Test Example 3.
  • FIG. 10 is a graph showing the measurement results of blood flow in ocular blood vessels due to ginger administration 20 minutes after endothelin-1 administration in Test Example 3.
  • FIG. 11 is a graph showing the measurement results of blood flow in ocular blood vessels due to ginger administration 20 minutes after endothelin-1 administration in Test Example 3.
  • FIG. 12 is a graph showing the measurement results of the blood flow rate of the eye blood vessels due to ginger administration after cold loading in Test Example 4.
  • composition for improving and/or maintaining ocular blood flow of the present invention contains ginger and/or an extract thereof.
  • Zingiber officinale is a perennial herbaceous plant belonging to the Zingiberaceae family. Ginger is known for its warming effects on the body, and has been consumed in countries around the world since ancient times. Ginger contains gingerol as a main component, and trace amounts of shogaol, dehydrogingerdione, and the like. Furthermore, ginger also contains trace amounts of more than 50 kinds of volatile fragrance oil components and more than 200 kinds of pungent components, and these main components and trace components bring about various physiological activities and improve lipid metabolism and arteries. Research is underway in the fields of sclerosis, cancer, allergies, arthritis, etc.
  • the part of ginger is not particularly limited as long as it achieves the effects of the present invention, but examples include at least one part selected from the group consisting of roots, stems, leaves, and flowers; , at least one selected from the group consisting of leaves, more preferably at least one selected from the group consisting of roots and stems, and even more preferably rhizomes.
  • the effects can be achieved using ginger and/or its extract.
  • the extraction method is not limited as long as the effects of the present invention are achieved.
  • ginger extract refers to the whole plant or the necessary parts of the plant (flowers, flower heads, flower buds, buds, spikes, leaves, branches, foliage, rhizomes, rhizomes, roots, bark, fruits). , pericarp, legumes, seeds, etc., preferably rhizomes), it may be used as it is, it may be further purified, it may be concentrated, it may be obtained by synthesis. , commercially available products can also be used.
  • the method for obtaining the plant extract is not particularly limited, and conventional extraction methods, purification methods, concentration methods, synthesis methods, dry powderization methods, etc. are employed.
  • the ginger extract is an extract obtained by immersion extraction of ginger or its pulverized product with water and/or an organic solvent and filtering the residue, an extract obtained by removing the solvent from this extract, Alternatively, it refers to these fine powders, or those obtained by dissolving, dispersing, or diluting the above-mentioned extract or solvent-removed product using an appropriate solvent, and it is also possible to use commercially available products.
  • the ginger extract can also be extracted after processing the ginger rhizome, such as steaming it. Further, the periderm of the rhizome may be removed, or it may be used as it is without removing it.
  • the extraction solvent includes water (including hot water), methanol, ethanol, isopropanol, ethylene glycol, 1,3- Alcohols such as butylene glycol and glycerin, esters such as ethyl acetate, ketones such as acetone and methyl ethyl ketone, nitriles such as acetonitrile, ethers such as diethyl ether and tetrahydrofuran, saturated substances such as pentane, hexane, cyclopentane, and cyclohexane.
  • water including hot water
  • methanol ethanol
  • isopropanol ethylene glycol
  • 1,3- Alcohols such as butylene glycol and glycerin
  • esters such as ethyl acetate, ketones such as acetone and methyl ethyl ketone
  • nitriles such as acetonitrile
  • ethers such as diethyl ether and
  • Hydrocarbons aromatic hydrocarbons such as toluene, halogenated hydrocarbons such as dichloromethane and chloroform, and other organic solvents such as dimethylformamide and dimethyl sulfoxide (all of which may contain water) can be used as appropriate. , or a mixture of two of them may be used. Among these solvents, water, ethanol, 1,3-butylene glycol, or a mixed solution thereof is preferred.
  • the extracts described herein can be obtained from various raw material companies, and are typically sold in a form that includes, but is not limited to, excipients.
  • the amount of extract refers to the dry solid content.
  • the extraction solvent for the ginger extract is not limited as long as it achieves the effects of the present invention, but water, ethanol, or aqueous ethanol is preferable, and aqueous ethanol is more preferable.
  • ginger extract powder Matsuura Pharmaceutical Co., Ltd.
  • ginger extract NE Ikeda Tokako Co., Ltd.
  • red ginger extract P Oryza Yuka Co., Ltd.
  • Co., Ltd. and Kintoki Ginger Powder (Koei Kogyo Co., Ltd.), but are not limited to these.
  • Ginger is also used as a herbal medicine in Chinese herbal preparations, and raw ginger is called ginger, dried raw ginger is called dried ginger, and steamed and dried ginger is called dried ginger. It is distinguished from (kankyo). Ginger in crude drugs is defined in the 18th edition of the Japanese Pharmacopoeia, and when it is quantified, it is [6]-gingerol (C 17 H 26 O 4 :294. 39) in an amount of 0.3% or more. Herbal medicines that meet the standards set by the Japanese Pharmacopoeia are commercially available, and such herbal medicines may be used in the present invention.
  • Red ginger Zingiber officinale Rubra.
  • Red ginger has a stronger spiciness than common white ginger, and is used as a spice and traditional medicine.
  • red ginger or red ginger extracts include, for example, red ginger powder (Ryusendo), Hokka Hokka red ginger powder (M&K Laboratories), red ginger extract P, and red ginger extract-WSP. , Red Ginger Extract-PC, Red Ginger Extract-WSPC, Red Ginger Extract-LC (all manufactured by Oryza Yuka Co., Ltd.), but are not limited to these.
  • the red ginger extract preferably contains 3.0% by mass or more of [6]-gingerol and [6]-shogaol, and preferably contains 6.0% by mass or more. More preferred. Further, it is preferable that the tannin content is 0.5% by mass or more in terms of procyanidin B2, and more preferably 1.5% by mass or more. Further, although not limited to, the excipient preferably contains cyclodextrin in an amount of 10% to 90%, more preferably 30% to 70% by weight, even more preferably 33% to 67% by weight. .
  • the content is, for example, 0.01% by mass or more, 0.05% by mass or more, 0.1% by mass based on the total amount of the composition. % or more, 0.3% by mass or more, 0.5 mass% or more, 1 mass% or more, 3 mass% or more, 5 mass% or more, 10 mass% or more, 20 mass% or more, and 90 mass% Below, the content may be 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 ginger extract is preferably 0.01 to 95% by mass, more preferably 0.05 to 70% by mass, even more preferably 0.1 to 50% by mass, particularly preferably 0. .5 to 30% by mass.
  • the content of ginger when using ginger, its content 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 based on the total amount of the composition. % mass% or more, 5 mass% or more, 10 mass% or more, 30 mass% or more, 50 mass% or more, and 99 mass% or less, 95 mass% or less, 90 mass% or less, 80 mass% or less, 70 mass% or more It may be less than 60% by mass, or less than 60% by mass.
  • the content of ginger is preferably 0.1 to 99% by mass, more preferably 0.5 to 95% by mass, even more preferably 1 to 90% by mass, and particularly preferably 3 to 80% by mass. It is.
  • the ratio of the herbal medicine is not limited, but for example, 1 to 100:1, 10 to 80:1, more preferably 20 to 60:1, even more preferably 30 to 45:1 (for example, 30 to 45:1). 1 kg of extract can be produced from 45 kg of ginger rhizome).
  • composition for improving and/or maintaining ocular blood flow of the present invention is also suitably used for improving conditions, symptoms, and diseases related to ocular blood flow.
  • examples Tet Examples
  • ocular blood flow reduction model rats ocular blood flow increases.
  • the present invention can also be used to maintain and promote the health of the vascular tissue in the eye.
  • the ophthalmic artery enters the optic nerve at the optic disc, and the central retinal artery and posterior ciliary artery deliver blood that nourishes the retina.
  • the ophthalmic artery branches into the short posterior ciliary artery, which receives blood flow at the optic nerve head and reaches the choroidal artery, which delivers blood that nourishes the outer layer of the retina.
  • the present invention provides anti-aging and improved health of the entire eye, including the eye tissue without vascular invasion, by increasing blood flow in the vascular tissue of the eye. and/or can be maintained.
  • the present invention can be applied to the eye. By increasing the blood flow rate of the vascular tissue, it is possible to improve, suppress the appearance or expansion (suppress the progression) of these conditions.
  • the present invention makes it possible to actively deliver blood components, including to the eye tissue without blood vessel invasion.
  • the circulation of tissue fluid also improves (improvement of tissue blood flow).
  • tissue blood flow tissue blood flow
  • tissue blood flow tissue blood flow
  • major retinal arteries such as the central retinal artery radiating from the optic disc were observed. It has been confirmed that not only vascular blood flow is improved, but also the circulation of capillaries and tissue fluid (tissue blood flow), and that overall blood flow in the eye area is improved.
  • the present invention is capable of increasing ocular blood flow, ocular tissue blood flow, and total ocular blood flow, thereby treating and/or preventing ocular circulation disorders. It can be used for any purpose.
  • ocular circulation disorders examples include glaucoma, retinal vein occlusion, retinal artery occlusion, ocular ischemic syndrome, internal carotid artery occlusion, renal retinopathy, transient amaurosis, and age-related macular degeneration. It will be done. Although not limited to, glaucoma, age-related macular degeneration, or retinal vein occlusion are preferred as the ocular circulation disorder from the viewpoint of increasing ocular blood flow, ocular tissue blood flow, and overall blood flow in the eye. .
  • the present invention has been confirmed to increase blood flow in the vascular tissue of the eye.
  • Those who are concerned about the circulation of blood (blood) those who want to improve the function of the optic nerve and muscles around the eye by improving the circulation of blood (blood) in the eye area, those who are concerned about the function of the optic nerve and muscles around the eye.
  • People who want to deliver blood to their eyes by improving blood circulation in the eye area people who want to support eye health, people who are concerned about lack of visual field, people who are concerned about narrowing of their visual field. It can also be suitably used for people who have difficulty seeing.
  • the present invention can be enclosed in a package in which these conditions and uses are clearly stated or evoked through words, illustrations, etc., and can be transferred to a consumer.
  • the eye region is lined with microscopic blood vessels, and microcirculation (microcirculation) is responsible for nourishing each tissue. Therefore, in one embodiment, the present invention can be suitably used for those who want to improve the microcirculation of the eye and those who are concerned about the microcirculation of the eye.
  • prevention refers to preventing or delaying the occurrence of a specific condition or disease, or reducing the risk of the occurrence of a specific condition or disease.
  • improvement refers to alleviation or improvement of a specific condition or disease, prevention or delay of deterioration of an abnormal condition, or prevention, delay, or reversal of the progression of a specific condition or disease.
  • the composition of the present invention can be added to or mixed with foods, drinks, medicines, feeds, and pet foods. Alternatively, it can be used as is as a drink or food. Or, the functions include improving ocular blood flow, protecting the retina, anti-aging of the eye, maintaining the health of the eye, improving vision, maintaining homeostasis of vascular tissue, reducing or preventing the risk of ocular circulation disorders, etc. It can be used explicitly or implicitly as a food or drink, that is, a health food, a food with functional claims, a food for the sick, or a food for specified health uses. Further, even if the above-mentioned functionality is not explicitly stated or implied, it can be used as a so-called doctor's supplement provided by a doctor at a hospital and/or clinic.
  • health foods, foods with functional claims, foods for the sick, and foods for specified health uses include solid preparations (tablets, orally disintegrating tablets, granules, fine granules, powders, capsules, chewable tablets, and candies). It can be used in various formulations such as liquid preparations (syrups, suspensions), liquid foods, etc.
  • Foods in the form of formulations can be produced in the same manner as known pharmaceutical preparations, and are produced by mixing the active ingredient and a food-acceptable carrier, such as an appropriate excipient, using conventional means. be able to.
  • the formulation form is not limited, it is preferably an orally disintegrating tablet, a chewable tablet, a candy, a granule, a powder, or a liquid from the viewpoint of achieving the effects of the present invention.
  • tablets can be prepared by compression molding a mixture of a powdered active ingredient and a pharmaceutically acceptable carrier component (such as an excipient), and confectionery tablets such as candies can be prepared by molding. It may also be prepared by injection. Tablets may be coated with sugar to form sugar-coated tablets. Furthermore, the tablet may be a single-layer tablet or a laminated tablet such as a two-layer tablet.
  • a pharmaceutically acceptable carrier component such as an excipient
  • confectionery tablets such as candies can be prepared by molding. It may also be prepared by injection. Tablets may be coated with sugar to form sugar-coated tablets.
  • the tablet may be a single-layer tablet or a laminated tablet such as a two-layer tablet.
  • Powder granules such as granules can be produced using various granulation methods (extrusion granulation, pulverization granulation, dry compaction granulation, fluidized bed granulation, rolling granulation, high-speed agitation granulation, etc.) Tablets can be prepared by appropriately combining the above-mentioned granulation method, tableting method (wet tableting method, direct tableting method), etc.
  • Capsules can be prepared by filling powders (powders, granules, etc.) into capsules (soft or hard capsules) by a conventional method.
  • Liquid preparations can be prepared by dissolving or dispersing each component in an aqueous medium (purified water, ethanol-containing purified water, etc.) as a carrier component, filtering or sterilizing it if necessary, filling it into a designated container, and sterilizing it.
  • aqueous medium purified water, ethanol-containing purified water, etc.
  • a preferred dosage form of the solid preparation of the present invention is a capsule or a tablet, and more preferably a soft capsule.
  • Soft capsules have a smooth surface and are easy to swallow, making them preferred by users.
  • Examples of common methods for producing soft capsules include a flat plate method, a rotary method, and a seamless method.
  • a sheet-like capsule film sandwiches the flowing filling contents and forms a capsule shape along the holes of a rotating cylindrical mold.
  • the seamless method dropping method
  • the capsule coating composition and the contents are simultaneously discharged from multiple concentric nozzles, forming a seamless capsule shape.
  • the base material for the film of the soft capsule is not particularly limited, but starch, pullulan, cellulose, polyvinyl alcohol, gelatin, succinated gelatin, etc. can be used, and starch, gelatin, and succinated gelatin are preferred, and gelatin, succinated gelatin, etc. Further preferred is gelatin. These may be used alone or in combination of two or more.
  • the composition of the present invention can be produced as beverages, liquid drinks such as diet drinks, semi-solid foods such as puddings and yogurt, noodles, confectionery, spreads, and the like.
  • various food additives may be added.
  • food additives include antioxidants, pigments, fragrances, seasonings, sweeteners, acidulants, pH adjusters, quality stabilizers, preservatives, and the like.
  • composition of the present invention is prepared as a pharmaceutical composition
  • it is prepared as a preparation containing the active ingredient, ginger and/or an extract thereof, and preferably a pharmaceutically acceptable carrier.
  • a pharmaceutically acceptable carrier generally refers to an inert, non-toxic, solid or liquid filler, diluent, or encapsulating material that does not react with the active ingredient, such as water. , ethanol, polyols, appropriate mixtures thereof, solvents or dispersion media such as vegetable oils, and the like.
  • the pharmaceutical composition is administered orally, parenterally, for example, into the oral cavity, into the gastrointestinal tract, or into the nasal cavity.
  • Orally administered preparations include solid preparations (tablets, orally disintegrating tablets, granules, fine granules, powders, capsules, chewable tablets, lozenges, etc.) and liquid preparations (syrups, suspensions, inhalants), etc. can be mentioned.
  • parenteral preparations include eye drops, drops, nasal drops, and injections.
  • the formulation form is not limited, it is preferably an orally disintegrating tablet, a chewable tablet, a candy, a granule, a powder, or a liquid from the viewpoint of achieving the effects of the present invention.
  • the pharmaceutical composition may further contain additives commonly used in the pharmaceutical field.
  • additives include, for example, excipients, binders, disintegrants, lubricants, antioxidants, coloring agents, and flavoring agents, which can be used as appropriate.
  • excipients for example, excipients, binders, disintegrants, lubricants, antioxidants, coloring agents, and flavoring agents, which can be used as appropriate.
  • binders for example, excipients, binders, disintegrants, lubricants, antioxidants, coloring agents, and flavoring agents, which can be used as appropriate.
  • coloring agents include, for example, binders, disintegrants, lubricants, antioxidants, coloring agents, and flavoring agents, which can be used as appropriate.
  • coloring agents for example, a known ethanol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbitol, sorbito
  • the pharmaceutical composition can be applied in the form of an oral composition, an internal composition, or the like.
  • the pharmaceutical compositions may also be used therapeutically or non-therapeutically.
  • the daily oral intake or dosage of ginger and/or its extract for adults depends on the condition of the individual, body weight, sex, age, activity of the material, route of intake or administration, schedule of intake or administration, formulation form, and other factors. It can be determined as appropriate depending on the following factors.
  • the daily oral intake or dosage of ginger and/or its 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, and 0.01 mg/kg body weight/day or more, for example. More preferably .05 mg/kg body weight/day or more, particularly preferably 0.1 mg/kg body weight/day or more.
  • the daily oral intake or dosage of ginger and/or its 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, and 2 mg/kg body weight/day. More preferably, the amount is less than 1 mg/kg body weight/day, particularly preferably less than 1 mg/kg body weight/day.
  • the daily oral intake or dosage of ginger and/or its extract for adults is, for example, preferably 0.01 to 10 mg/kg body weight/day, more preferably 0.02 to 5 mg/kg body weight/day. , 0.05 to 2 mg/kg body weight/day is more preferred, and 0.1 to 1 mg/kg body weight/day is particularly preferred.
  • the content of ginger and/or its extract can be set to the above-mentioned intake or administration amount.
  • the daily oral intake or dosage of ginger extract for adults is, for example, preferably 0.5 mg/day or more, more preferably 1 mg/day or more, and 3 mg/day or more. More preferably, 5 mg/day or more is particularly preferred, and 10 mg/day or more is most preferred.
  • the daily oral intake or dosage of ginger extract for adults is, for example, preferably 500 mg/day or less, more preferably 200 mg/day or less, even more preferably 100 mg/day or less, particularly preferably 50 mg/day or less. .
  • the daily oral intake or dosage of ginger extract for adults is, for example, preferably 0.5 to 500 mg/day, more preferably 1 to 200 mg/day, even more preferably 3 to 100 mg/day. , 5 to 50 mg/day or less is particularly preferred.
  • the daily oral intake or dosage of ginger for adults is, for example, preferably 20 mg/day or more, more preferably 40 mg/day or more, even more preferably 120 mg/day or more, and 200 mg/day or more. /day or more is particularly preferred, and 400 mg/day or more is most preferred.
  • the daily oral intake or dosage of ginger for adults is, for example, preferably 5000 mg/day or less, more preferably 3000 mg/day or less, even more preferably 1000 mg/day or less, and particularly preferably 800 mg/day or less.
  • the oral intake or dosage of ginger is, for example, preferably 20 to 5000 mg/day or less, more preferably 40 to 3000 mg/day, even more preferably 120 to 1000 mg/day, particularly 200 to 800 mg/day. preferable.
  • the effective dose for animals is converted to the human dose as the dose per kg of body weight, and the dose is 1/60 or less.
  • This method can be used. That is, if the effective dose for animals is X mg/kg, the dose for humans (mg/day) can be calculated as follows: X (mg) x body weight (kg)/60-600.
  • the daily oral intake or dosage of ginger and/or its extract for adults is, 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, 10 mg/day or more, and 1000 mg/day or less, 900 mg/day or less, 800 mg/day or less, 700 mg/day or less, 600 mg/day or less, 500 mg/day or less, 400 mg/day or less, 300 mg/day or less, 200 mg/day or less, 150 mg/day or less, 100 mg/day or less, 75 mg/day or less, 50 mg/day or less, It can also be 30 mg/day or less, 20 mg/day or less, or 10 mg/day or less.
  • oral intake or dosage per day for adults is 1 to 6 capsules, 1 to 4 capsules, 1 to 3 capsules, or 1 to 2 capsules depending on the dosage form. May be taken separately.
  • composition of the present invention is divided into once to several times a day, usually taken or administered 1 to 6 times a day, 1 to 3 times a day, 1 to 2 times a day, or at any period and interval. However, once a day is preferred.
  • the present invention may also have the following aspects.
  • a composition for improving and/or maintaining ocular blood flow containing ginger and/or an extract thereof;
  • a composition for maintaining the health of vascular tissue in the eye containing ginger and/or an extract thereof;
  • An anti-aging composition for the eye region containing ginger and/or an extract thereof;
  • a composition for the treatment and/or prevention of ocular circulation disorders containing ginger and/or an extract thereof;
  • Compositions containing ginger and/or extracts thereof for use in improving and/or maintaining ocular blood flow A composition containing ginger and/or an extract thereof for use in maintaining the health of vascular tissue of the eye;
  • Compositions containing ginger and/or extracts thereof for use in anti-aging of the eye Compositions containing ginger and/or extracts thereof for use in improving and/or maintaining ocular
  • the above composition which is a pharmaceutical product or a food or drink product;
  • the above composition, use, or method, wherein the dosage form is an orally disintegrating tablet, a chewable tablet, a lozenge, a granule, a powder, or a liquid;
  • the above composition, use, or method, wherein the ginger is red ginger;
  • the above composition, use, or method, wherein the ginger and/or extract thereof is red ginger and/or an extract thereof;
  • the above composition, use, or method, wherein the ginger part comprises a rhizome;
  • the above composition, use, or method, wherein the extraction solvent in the ginger extract is aqueous ethanol;
  • the above 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 above composition, use, or method, wherein the total content of [6]-gingerol and [6]-shogaol in red ginger is
  • the present invention will be specifically explained with reference to Examples, but the present invention is not limited to the following Examples.
  • the amount of extract shown in the Examples is the amount calculated in terms of dry solid content and including excipients and the like.
  • red ginger extract powder red ginger extract-P, manufactured by Oryza Yuka Co., Ltd., indicated as "O-2" in the figure, the same hereinafter
  • O-2 red ginger extract powder
  • Figure 1 shows the measurement results of the baseline ocular blood flow and the ocular blood flow after ingestion of the test sample.
  • eight rats were used in each administration group, and statistical processing was performed using the Holm-Sidak test.
  • AveALL (V) in the figure indicates the blood flow rate (MBR average value, the same applies hereinafter) in the blood vessel region.
  • control group The same as the above oral administration group except that red ginger extract powder was not administered. Specifically, 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. 10 and 20 minutes after endothelin-1 administration, ocular blood flow was determined by laser speckle flowgraphy (AveALL (A): blood flow in the entire region, AveALL (V): blood flow in the vascular region, AveALL (T): tissue region blood flow rate), pulse rate, mean blood pressure, and intraocular pressure were measured.
  • A blood flow in the entire region
  • AveALL (V) blood flow in the vascular region
  • AveALL (T) tissue region blood flow rate
  • pulse rate mean blood pressure
  • intraocular pressure intraocular pressure
  • the posterior segment blood flow map 10 minutes after endothelin-1 administration is shown in FIG. 4, and the graphs after analysis are shown in FIGS. 5 to 7. Statistical processing was performed using the student-t test. Further, the posterior ocular blood flow map 20 minutes after endothelin-1 administration is shown in FIG. 8, and the graphs after analysis are shown in FIGS. 9 to 11. Statistical processing was performed using the student-t test.
  • E1 endothelin-1
  • endothelin-1 (ET1) models glaucoma, which reduces ocular blood flow. Therefore, it was suggested that, although not limited to, ingesting (administering) ginger is suitable for treating and/or preventing glaucoma among ocular circulation disorders.
  • Test Example 4 Ocular blood flow evaluation test after cold load in humans
  • heat radiation from skin blood vessels is suppressed, causing vasoconstriction and a decrease in blood flow.
  • blood flow recovers over time. These phenomena are said to occur with regard to ocular blood flow in humans who are highly sensitive to cold stress.
  • Test Examples 2 and 3 by using laser speckle flowgraphy, it becomes possible to quantitatively evaluate changes in ocular blood flow.
  • a substance that can shorten the blood flow recovery period after a cold load will contribute to improving and/or maintaining ocular blood flow, maintain the health of the vascular tissue in the eye, anti-aging the eye, visual field narrowing, and visual field loss.
  • red ginger extract-P manufactured by Oryza Yuka Co., Ltd.
  • Healthy subjects were brought into the test room and seated in a chair in the test room at a room temperature of 24 to 25°C, allowed to rest for 30 minutes and acclimatized to the test environment, and then allowed to ingest or not ingest the test food. The subjects were then seated in a chair in a test room at a room temperature of 24-25°C and allowed to rest for 30 minutes. Then, as in Test Examples 2 and 3, the ocular blood flow before loading was measured using laser speckle flowgraphy (LSFG-NAVI, manufactured by Softcare Co., Ltd.) and the attached analysis application (LSFG analyzer). Blood flow values (initial values) before cold loading were obtained.
  • LSFG-NAVI laser speckle flowgraphy
  • LSFG analyzer attached analysis application
  • the subjects were allowed to ingest the test food 30 minutes before the cold load or were not ingested, and were allowed to sit on a chair in a test room at a room temperature of 24 to 25°C and rest for 30 minutes.
  • the content of the red ginger extract itself (without excipients) in the test food was approximately 10 mg/day as a dry solid content.
  • a nitrile glove was put on the right hand, and the right wrist was immersed in warm water at 40°C for 2 minutes. Thereafter, the right wrist was immersed in cold water at 4° C. for 1 minute to perform a cold load. After the cold load, moisture was immediately wiped off with a paper towel or the like, and fundus blood flow was measured 4 and 6 minutes after the cold load. A similar test was conducted on the same subjects under crossover conditions with a sufficient washout period.
  • the fundus blood flow measurement in this test example measures the blood flow rate (MBR average value) in the tissue region of the optic nerve head.
  • MBR average value blood flow rate
  • subjects whose optic disc temperature decreased were evaluated as responders (nine subjects in this study).
  • the results are shown in FIG.
  • the upper line graph is the test food group, and the lower line graph is the non-ingestion group.
  • the vertical axis indicates the average value of the amount of change in MBR.
  • ginger red ginger extract
  • the ocular blood flow could be increased and the blood flow recovery period could be shortened after a cold load, compared to the control group. Therefore, ginger (red ginger extract) contributes to improving and/or maintaining ocular blood flow, maintains the health of the vascular tissue in the eye, anti-aging the eye, and prevents visual field narrowing, visual field defects, scotoma, etc. It is expected to be effective in the treatment and/or prevention of various ocular circulation disorders.
  • the red ginger extract (red ginger extract-P, manufactured by Oryza Yuka Co., Ltd.) used in the above examples was extracted from the rhizome with aqueous ethanol, and the total content of [6]-gingerol and [6]-shogaol was 6. .0% by mass or more, tannins in an amount of 1.5% by mass or more, and an equal amount of cyclodextrin mixed as an excipient.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Ophthalmology & Optometry (AREA)
  • Nutrition Science (AREA)
  • Botany (AREA)
  • Polymers & Plastics (AREA)
  • Food Science & Technology (AREA)
  • Mycology (AREA)
  • Epidemiology (AREA)
  • Vascular Medicine (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Urology & Nephrology (AREA)
  • Microbiology (AREA)
  • Medical Informatics (AREA)
  • Biotechnology (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Medicines Containing Plant Substances (AREA)

Abstract

The purpose of the present invention is to provide a composition that improves conditions related to ocular blood flow by evaluating effects on ocular blood flow. Provided is a composition for improving and/or maintaining ocular blood flow, said composition containing Zingiber officinale and/or an extract thereof. Also provided are a composition for maintaining the health of vascular tissues in the ocular region, a composition for anti-aging of the ocular region, a composition for improving and/or maintaining the health of the ocular region, visual field narrowing, visual field defects or the appearance or expansion of a dark spot, and a composition for treating and/or preventing ocular circulation disorders, each composition containing the aforesaid ingredient.

Description

眼血流改善用組成物Composition for improving ocular blood flow
　本発明は眼血流改善用組成物に関する。詳細には、眼血流の改善及び／又は維持用組成物、眼部の血管組織の健常性維持用組成物、眼部の抗老化用組成物、眼部の健常性、視野狭窄、視野欠損、若しくは暗点の出現又は拡大の改善及び／又は維持用の組成物、眼循環障害の治療及び／又は予防用の組成物に関する。 The present invention relates to a composition for improving ocular blood flow. In detail, compositions for improving and/or maintaining ocular blood flow, compositions for maintaining the health of vascular tissue in the eye, anti-aging compositions for the eye, health of the eye, visual field narrowing, visual field defects. , or compositions for improving and/or maintaining the appearance or expansion of scotoma, and compositions for treating and/or preventing ocular circulation disorders.
　ショウガ科植物（Zingiberaceae）は、１６００種ほどが知られており、ショウガ（Zingiber officinale）、ミョウガ（Zingiber mioga）、ウコン（Curcuma）等、香辛料や機能性素材で用いられている。 There are approximately 1,600 known species of plants in the Zingiberaceae family, and they are used in spices and functional materials such as Zingiber officinale, Zingiber mioga, and Curcuma.
　ショウガには、ジンゲロール（gingerol）が主成分として含まれ、ショウガオール（shogaol）やデヒドロジンジャージオン（dehydrogingerdione）等も含まれている。ショウガは、これらの成分から多種の効能が知られており、消化不良の改善、乗り物酔いの改善、糖尿病治療、鎮痛剤等への使用が提案されている（特許文献１）。 Ginger contains gingerol as a main component, and also contains shogaol, dehydrogingerdione, etc. Ginger is known to have various effects due to these components, and its use has been proposed for improving indigestion, motion sickness, diabetes treatment, analgesic, etc. (Patent Document 1).
特表２００５－５１１６４１号公報Special Publication No. 2005-511641
　しかしながら、ショウガの眼領域への利用については、まだ十分な報告がない状況である。 However, there are still not enough reports regarding the use of ginger for the eye area.
　そこで、本発明は、ショウガを眼領域に用いた場合の眼血流に対する作用を評価し、眼血流に関連する状態を改善する組成物を提供することを目的とする。 Therefore, the present invention aims to evaluate the effect on ocular blood flow when ginger is used in the eye region, and to provide a composition that improves conditions related to ocular blood flow.
　上記課題を解決するために、本発明者等が鋭意検討した結果、食品分野や医薬品分野において、安全に使用されているショウガ及び／又はその抽出物において、眼血流の改善及び／又は維持に対する活性等を有することを見出し、本発明を完成するに至った。 In order to solve the above-mentioned problems, the present inventors conducted intensive studies and found that ginger and/or its extracts, which are safely used in the food and pharmaceutical fields, are effective in improving and/or maintaining ocular blood flow. The present inventors have discovered that the compound has activity, etc., and have completed the present invention.
　すなわち、本発明は、下記に掲げる組成物を提供する。 That is, the present invention provides the following compositions.
　［１］ショウガ及び／又はその抽出物を含有する、眼血流の改善及び／又は維持用組成物。 [1] A composition for improving and/or maintaining ocular blood flow, containing ginger and/or an extract thereof.
　［２］ショウガ及び／又はその抽出物を含有する、眼部の血管組織の健常性維持用組成物。 [2] A composition for maintaining the health of vascular tissue in the eye, containing ginger and/or an extract thereof.
　［３］ショウガ及び／又はその抽出物を含有する、眼部の抗老化用組成物。 [3] An eye anti-aging composition containing ginger and/or an extract thereof.
　［４］ショウガ及び／又はその抽出物を含有する、眼部の健常性、視野狭窄、視野欠損、若しくは暗点の出現又は拡大の改善及び／又は維持用の組成物。 [4] A composition for improving and/or maintaining ocular health, visual field narrowing, visual field defect, or appearance or expansion of scotoma, containing ginger and/or its extract.
　［５］ショウガ及び／又はその抽出物を含有する、眼循環障害の治療及び／又は予防用の組成物。 [5] A composition for treating and/or preventing ocular circulation disorders, containing ginger and/or an extract thereof.
　［６］眼循環障害が、緑内障、網膜静脈閉塞症、網膜動脈閉塞症、眼虚血症候群、内頚動脈閉塞症、腎性網膜症、一過性黒内障、又は、加齢黄斑変性である［５］に記載の組成物。 [6] The ocular circulation disorder is glaucoma, retinal vein occlusion, retinal artery occlusion, ocular ischemic syndrome, internal carotid artery occlusion, renal retinopathy, transient amaurosis, or age-related macular degeneration [5 The composition described in ].
　［７］医薬品又は飲食品である、［１］～［６］のいずれか１に記載の組成物。 [7] The composition according to any one of [1] to [6], which is a pharmaceutical or a food or drink.
　［８］口腔内崩壊錠、チュアブル錠、飴剤、顆粒剤、散剤又は液剤である［７］に記載の組成物。 [8] The composition according to [7], which is an orally disintegrating tablet, a chewable tablet, a candy, a granule, a powder, or a liquid.
　［９］ショウガ及び／又はその抽出物が、アカショウガ及び／又はその抽出物である、
［１］～［８］のいずれか１に記載の組成物。 [9] Ginger and/or its extract is red ginger and/or its extract,
The composition according to any one of [1] to [8].
　［１０］眼血流が、網膜及び／又は脈絡膜の血流である、［１］に記載の組成物。 [10] The composition according to [1], wherein the ocular blood flow is retinal and/or choroidal blood flow.
　本発明によれば、食品分野や医薬品分野において、安全に使用されているショウガ及び／又はその抽出物により眼血流を改善させ、関連する眼の状態を効果的に改善することが可能となる。 According to the present invention, it is possible to improve ocular blood flow and effectively improve related ocular conditions using ginger and/or its extract, which is safely used in the food and pharmaceutical fields. .
図１は、試験例２における、ショウガ投与による眼部血管の血流量の測定結果を示すグラフである。FIG. 1 is a graph showing the measurement results of blood flow in ocular blood vessels due to ginger administration in Test Example 2. 図２は、試験例３における、眼血流低下型モデルの検討結果を示す後眼部写真である。FIG. 2 is a photograph of the posterior segment of the eye showing the results of an examination of the ocular blood flow reduction type model in Test Example 3. 図３は、試験例３における、眼血流低下型モデルの検討結果を示すグラフである。FIG. 3 is a graph showing the study results of the ocular blood flow reduction type model in Test Example 3. 図４は、試験例３における、エンドセリン－１投与から１０分後における、ショウガ投与による影響を評価した後眼部写真である。FIG. 4 is a photograph of the posterior segment of the eye 10 minutes after endothelin-1 administration in Test Example 3, in which the influence of ginger administration was evaluated. 図５は、試験例３における、エンドセリン－１投与から１０分後における、ショウガ投与による眼部血管の血流量の測定結果を示すグラフである。FIG. 5 is a graph showing the measurement results of blood flow in ocular blood vessels due to ginger administration 10 minutes after endothelin-1 administration in Test Example 3. 図６は、試験例３における、エンドセリン－１投与から１０分後における、ショウガ投与による眼部血管の血流量の測定結果を示すグラフである。FIG. 6 is a graph showing the measurement results of blood flow in ocular blood vessels due to ginger administration 10 minutes after endothelin-1 administration in Test Example 3. 図７は、試験例３における、エンドセリン－１投与から１０分後における、ショウガ投与による眼部血管の血流量の測定結果を示すグラフである。FIG. 7 is a graph showing the measurement results of blood flow in ocular blood vessels due to ginger administration 10 minutes after endothelin-1 administration in Test Example 3. 図８は、試験例３における、エンドセリン－１投与から２０分後における、ショウガ投与による影響を評価した後眼部写真である。FIG. 8 is a photograph of the posterior segment of the eye 20 minutes after endothelin-1 administration in Test Example 3, in which the influence of ginger administration was evaluated. 図９は、試験例３における、エンドセリン－１投与から２０分後における、ショウガ投与による眼部血管の血流量の測定結果を示すグラフである。FIG. 9 is a graph showing the measurement results of blood flow in ocular blood vessels due to ginger administration 20 minutes after endothelin-1 administration in Test Example 3. 図１０は、試験例３における、エンドセリン－１投与から２０分後における、ショウガ投与による眼部血管の血流量の測定結果を示すグラフである。FIG. 10 is a graph showing the measurement results of blood flow in ocular blood vessels due to ginger administration 20 minutes after endothelin-1 administration in Test Example 3. 図１１は、試験例３における、エンドセリン－１投与から２０分後における、ショウガ投与による眼部血管の血流量の測定結果を示すグラフである。FIG. 11 is a graph showing the measurement results of blood flow in ocular blood vessels due to ginger administration 20 minutes after endothelin-1 administration in Test Example 3. 図１２は、試験例４における、寒冷負荷後における、ショウガ投与による眼部血管の血流量の測定結果を示すグラフである。FIG. 12 is a graph showing the measurement results of the blood flow rate of the eye blood vessels due to ginger administration after cold loading in Test Example 4.
　［眼血流の改善及び／又は維持用組成物］
　一つの実施形態において、本発明の眼血流の改善及び／又は維持用組成物は、ショウガ及び／又はその抽出物を含有する。 [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 an extract thereof.
　（ショウガ及び／又はその抽出物）
　ショウガ（Zingiber officinale）は、ショウガ科に属する多年生草本植物である。ショウガは、身体を温める作用等が知られ、世界各国で古くから摂取されている。ショウガには、主成分としてジンゲロール（gingerol）を含有し、微量にショウガオール（shogaol）やデヒドロジンジャージオン（dehydrogingerdione）等を含有している。さらに、ショウガには、微量な５０種類以上の揮発性香油成分、２００種類以上の刺激性辛み成分も含まれており、これらの主成分や微量成分が様々な生理活性をもたらし、脂質代謝、動脈硬化、がん、アレルギー、関節炎等の分野において研究が進められている。 (Ginger and/or its extract)
Zingiber officinale is a perennial herbaceous plant belonging to the Zingiberaceae family. Ginger is known for its warming effects on the body, and has been consumed in countries around the world since ancient times. Ginger contains gingerol as a main component, and trace amounts of shogaol, dehydrogingerdione, and the like. Furthermore, ginger also contains trace amounts of more than 50 kinds of volatile fragrance oil components and more than 200 kinds of pungent components, and these main components and trace components bring about various physiological activities and improve lipid metabolism and arteries. Research is underway in the fields of sclerosis, cancer, allergies, arthritis, etc.
　ショウガの部位としては、本発明の効果を奏する限り、特に限定はされないが、例えば、根、茎、葉、及び、花からなる群より選択される少なくとも１種が挙げられ、根、茎、及び、葉からなる群より選択される少なくとも１種が好ましく、根、及び、茎からなる群より選択される少なくとも１種がより好ましく、根茎が更に好ましい。 The part of ginger is not particularly limited as long as it achieves the effects of the present invention, but examples include at least one part selected from the group consisting of roots, stems, leaves, and flowers; , at least one selected from the group consisting of leaves, more preferably at least one selected from the group consisting of roots and stems, and even more preferably rhizomes.
　本発明においては、ショウガ及び／又はその抽出物を用いて効果を奏することができる。一つの実施態様において、ショウガの抽出物（ショウガエキス）を用いる場合においては、本発明の効果を奏する限り、抽出方法は限定されない。 In the present invention, the effects can be achieved using ginger and/or its extract. In one embodiment, when using a ginger extract, the extraction method is not limited as long as the effects of the present invention are achieved.
　本明細書において、ショウガの抽出物（ショウガエキス）は、植物の全草あるいは必要部位（花、頭花、花芽、つぼみ、花穂、葉、枝、枝葉、根茎、根皮、根、樹皮、果実、果皮、豆果、種子などいずれでもよい、好ましくは根茎）から抽出した粗抽出物そのままでも、更にそれを精製処理したものでも良く、濃縮処理したものでも良く、合成によって得られたものでも良く、市販品を用いることもできる。植物のエキスを得る方法としては、特に限定されず、通常の抽出法、精製方法、濃縮方法、合成方法、乾燥粉末化方法等が採用される。 In this specification, ginger extract (ginger extract) refers to the whole plant or the necessary parts of the plant (flowers, flower heads, flower buds, buds, spikes, leaves, branches, foliage, rhizomes, rhizomes, roots, bark, fruits). , pericarp, legumes, seeds, etc., preferably rhizomes), it may be used as it is, it may be further purified, it may be concentrated, it may be obtained by synthesis. , commercially available products can also be used. The method for obtaining the plant extract is not particularly limited, and conventional extraction methods, purification methods, concentration methods, synthesis methods, dry powderization methods, etc. are employed.
　一例として、ショウガの抽出物は、ショウガ又はその粉砕物から、水及び／又は有機溶媒で浸漬抽出し、残査を濾別することにより得られる抽出液、この抽出液から溶媒を除去したもの、あるいはこれらの微粉末、又は、上記抽出液や溶媒除去物を適当な溶剤を用いるなどして溶解、分散、希釈したものなどをいい、市販品を用いることも可能である。他の抽出方法の例として、ショウガの抽出物は、ショウガの根茎を蒸す等の加工を施した後に抽出することも可能である。また、根茎の周皮は除いたものであってもよく、除かずにそのまま用いてもよい。 As an example, the ginger extract is an extract obtained by immersion extraction of ginger or its pulverized product with water and/or an organic solvent and filtering the residue, an extract obtained by removing the solvent from this extract, Alternatively, it refers to these fine powders, or those obtained by dissolving, dispersing, or diluting the above-mentioned extract or solvent-removed product using an appropriate solvent, and it is also possible to use commercially available products. As an example of another extraction method, the ginger extract can also be extracted after processing the ginger rhizome, such as steaming it. Further, the periderm of the rhizome may be removed, or it may be used as it is without removing it.
　本明細書において、植物の抽出物（植物のエキスともいう）を用いる場合、より詳細には、抽出溶媒として、水（熱水を含む）、メタノール、エタノール、イソプロパノール、エチレングリコール、１，３－ブチレングリコール、グリセリン等のアルコール類、酢酸エチル等のエステル類、アセトンやメチルエチルケトン等のケトン類、アセトニトリルなどのニトリル類、ジエチルエーテル、テトラヒドロフラン等のエーテル類、ペンタン、ヘキサン、シクロペンタン、シクロヘキサンなどの飽和炭化水素類、トルエンなどの芳香族炭化水素類、ジクロロメタン、クロロホルムなどのハロゲン化炭化水素類、その他ジメチルホルムアミド、ジメチルスルホキシドなどの有機溶媒（すべて含水であってもよい）などを適宜用いることができ、１種または２種の任意の混合液であってもよい。これらの溶媒のうち、水、エタノール、１，３－ブチレングリコールまたはこれらの混合溶液が好ましい。本明細書に記載の抽出物は、各種原料品会社から入手することができ、それらは通常、賦形剤を含めた形で販売されている場合が多いが限定はされない。以下、抽出物量とは、乾燥固形分含量をいう。 In this specification, when using a plant extract (also referred to as a plant extract), more specifically, the extraction solvent includes water (including hot water), methanol, ethanol, isopropanol, ethylene glycol, 1,3- Alcohols such as butylene glycol and glycerin, esters such as ethyl acetate, ketones such as acetone and methyl ethyl ketone, nitriles such as acetonitrile, ethers such as diethyl ether and tetrahydrofuran, saturated substances such as pentane, hexane, cyclopentane, and cyclohexane. Hydrocarbons, aromatic hydrocarbons such as toluene, halogenated hydrocarbons such as dichloromethane and chloroform, and other organic solvents such as dimethylformamide and dimethyl sulfoxide (all of which may contain water) can be used as appropriate. , or a mixture of two of them may be used. Among these solvents, water, ethanol, 1,3-butylene glycol, or a mixed solution thereof is preferred. The extracts described herein can be obtained from various raw material companies, and are typically sold in a form that includes, but is not limited to, excipients. Hereinafter, the amount of extract refers to the dry solid content.
　ショウガ抽出物の抽出溶媒は、本発明の効果を奏する限り、制限されないが、水、エタノール、または含水エタノールであることが好ましく、含水エタノールであることがより好ましい。 The extraction solvent for the ginger extract is not limited as long as it achieves the effects of the present invention, but water, ethanol, or aqueous ethanol is preferable, and aqueous ethanol is more preferable.
　ショウガを含有する食品素材、又は、ショウガ抽出物の市販品としては、例えば、ショウガエキス末（松浦薬業株式会社）、ジンジャーエキスＮＥ（池田糖化工株式会社）、赤ショウガエキスＰ（オリザ油化株式会社）、金時ショウガ末（香栄興業株式会社）などがあるが、これらに限定されない。 Commercially available food materials or ginger extracts containing ginger include, for example, ginger extract powder (Matsuura Pharmaceutical Co., Ltd.), ginger extract NE (Ikeda Tokako Co., Ltd.), and red ginger extract P (Oryza Yuka Co., Ltd.). Co., Ltd.) and Kintoki Ginger Powder (Koei Kogyo Co., Ltd.), but are not limited to these.
　また、ショウガは生薬として漢方製剤に用いられており、生のショウガを生姜（ショウキョウ）、生のショウガをそのまま乾燥させたものを乾生姜（カンショウキョウ）、蒸して乾燥させたものを乾姜（カンキョウ）と区別されている。生薬における生姜（ショウキョウ）は、第十八改正日本薬局方に定義されたとおり、定量するとき、換算した生薬の乾燥物に対して［６］‐ギンゲロール（Ｃ１７Ｈ２６Ｏ４：２９４．３９）を０．３％以上含むものである。日本薬局方に定められた規格の生薬が市販されており、本発明においてこのような各生薬を用いてもよい。 Ginger is also used as a herbal medicine in Chinese herbal preparations, and raw ginger is called ginger, dried raw ginger is called dried ginger, and steamed and dried ginger is called dried ginger. It is distinguished from (kankyo). Ginger in crude drugs is defined in the 18th edition of the Japanese Pharmacopoeia, and when it is quantified, it is [6]-gingerol (C 17 H 26 O 4 :294. 39) in an amount of 0.3% or more. Herbal medicines that meet the standards set by the Japanese Pharmacopoeia are commercially available, and such herbal medicines may be used in the present invention.
　限定はされないが、ショウガとしては、アカショウガ（Zingiber officinale Rubra.）を用いることも可能である。アカショウガは、一般的なシロショウガと比較して辛みが強く、スパイスや伝統医薬品等としても用いられている。 Although not limited, it is also possible to use red ginger (Zingiber officinale Rubra.) as the ginger. Red ginger has a stronger spiciness than common white ginger, and is used as a spice and traditional medicine.
　アカショウガを含有する食品素材、又は、アカショウガ抽出物の市販品としては、例えば、赤香ショウガ粉末（龍泉堂）、ほっかほっか赤ショウガ粉末（Ｍ＆Ｋ　ラボラトリーズ）、赤ショウガエキスＰ、赤ショウガエキス-ＷＳＰ、赤ショウガエキス-ＰＣ、赤ショウガエキス-ＷＳＰＣ、赤ショウガエキス-ＬＣ（以上、オリザ油化株式会社）、などがあるが、これらに限定されない。 Commercially available food materials containing red ginger or red ginger extracts include, for example, red ginger powder (Ryusendo), Hokka Hokka red ginger powder (M&K Laboratories), red ginger extract P, and red ginger extract-WSP. , Red Ginger Extract-PC, Red Ginger Extract-WSPC, Red Ginger Extract-LC (all manufactured by Oryza Yuka Co., Ltd.), but are not limited to these.
　限定はされないが、アカショウガの抽出物としては、［６］－ｇｉｎｇｅｒｏｌおよび［６］－ｓｈｏｇａｏｌの含有量が３．０質量％以上であるものが好ましく、６．０質量％以上含有するものがより好ましい。また、タンニンの含有量がプロシアニジンＢ２換算で０．５質量％以上であるものが好ましく、１．５質量％以上含有するものがより好ましい。また、限定はされないが、賦形剤として、シクロデキストリンを好ましくは１０％～９０％、より好ましくは３０質量％～７０質量％、さらにより好ましくは３３質量％～６７質量％含量するものがよい。 Although not limited, the red ginger extract preferably contains 3.0% by mass or more of [6]-gingerol and [6]-shogaol, and preferably contains 6.0% by mass or more. More preferred. Further, it is preferable that the tannin content is 0.5% by mass or more in terms of procyanidin B2, and more preferably 1.5% by mass or more. Further, although not limited to, the excipient preferably contains cyclodextrin in an amount of 10% to 90%, more preferably 30% to 70% by weight, even more preferably 33% to 67% by weight. .
　本発明の効果を顕著に奏する観点から、ショウガ抽出物を用いる場合、その含有量は、例えば、組成物全量に対して、０．０１質量％以上、０．０５質量％以上、０．１質量％以上、０．３％質量％以上、０．５質量％以上、１質量％以上、３質量％以上、５質量％以上、１０質量％以上、２０質量％以上であってよく、９０質量％以下、５０質量％以下、２５質量％以下、１０質量％以下、５質量％以下、３質量％以下、１質量％以下であってもよい。ショウガ抽出物の含有量は、好ましくは０．０１～９５質量％であり、より好ましくは０．０５～７０質量％であり、更に好ましくは０．１～５０質量％であり、特に好ましくは０．５～３０質量％である。 From the viewpoint of significantly achieving the effects of the present invention, when using ginger extract, the content is, for example, 0.01% by mass or more, 0.05% by mass or more, 0.1% by mass based on the total amount of the composition. % or more, 0.3% by mass or more, 0.5 mass% or more, 1 mass% or more, 3 mass% or more, 5 mass% or more, 10 mass% or more, 20 mass% or more, and 90 mass% Below, the content may be 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 ginger extract is preferably 0.01 to 95% by mass, more preferably 0.05 to 70% by mass, even more preferably 0.1 to 50% by mass, particularly preferably 0. .5 to 30% by mass.
　本発明の効果を顕著に奏する観点から、ショウガを用いる場合、その含有量は、例えば、組成物全量に対して、０．１質量％以上、０．５質量％以上、１質量％以上、３％質量％以上、５質量％以上、１０質量％以上、３０質量％以上、５０質量％以上であってよく、９９質量％以下、９５質量％以下、９０質量％以下、８０質量％以下、７０質量％以下、６０質量％以下であってもよい。ショウガの含有量は、好ましくは０．１～９９質量％であり、より好ましくは０．５～９５質量％であり、更に好ましくは１～９０質量％であり、特に好ましくは３～８０質量％である。 From the viewpoint of significantly achieving the effects of the present invention, when using ginger, its content 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 based on the total amount of the composition. % mass% or more, 5 mass% or more, 10 mass% or more, 30 mass% or more, 50 mass% or more, and 99 mass% or less, 95 mass% or less, 90 mass% or less, 80 mass% or less, 70 mass% or more It may be less than 60% by mass, or less than 60% by mass. The content of ginger is preferably 0.1 to 99% by mass, more preferably 0.5 to 95% by mass, even more preferably 1 to 90% by mass, and particularly preferably 3 to 80% by mass. It is.
　ショウガ抽出物の場合、原生薬比率は限定されないが、例えば、１～１００：１、１０～８０：１、より好ましくは２０～６０：１、さらに好ましくは３０～４５：１（例えば、３０ｋｇ～４５ｋｇのショウガ根茎から１ｋｇのエキスができる）等が挙げられる。 In the case of ginger extract, the ratio of the herbal medicine is not limited, but for example, 1 to 100:1, 10 to 80:1, more preferably 20 to 60:1, even more preferably 30 to 45:1 (for example, 30 to 45:1). 1 kg of extract can be produced from 45 kg of ginger rhizome).
　［用途］
　本発明の眼血流の改善及び／又は維持用組成物は、眼血流と関連のある状態、症状、疾患の改善にも好適に用いられる。後述の実施例（試験例）において、本発明の組成物を、健常ラット、及び、眼血流低下モデルラットに経口により摂取させた場合、眼血流が増加することが確認されている。また、当該試験例において、ラットの他の全身状態や眼状態（脈拍、平均血圧、眼圧等）へは影響を与えなかったことが確認されている。 [Application]
The composition for improving and/or maintaining ocular blood flow of the present invention is also suitably used for improving conditions, symptoms, and diseases related to ocular blood flow. In the Examples (Test Examples) described below, it has been confirmed that when the composition of the present invention is orally ingested by healthy rats and ocular blood flow reduction model rats, ocular blood flow increases. Furthermore, in this test example, it was confirmed that there was no effect on other general conditions or eye conditions (pulse, average blood pressure, intraocular pressure, etc.) of the rats.
　本発明の組成物を用いることにより、眼血流を増加させ、眼血流が低下することを抑制し、又は、眼血流を維持することが可能となる。このように、眼部の血流を増加させることができるため、一つの実施形態において、本発明は、眼部の血管組織の健常性を維持、増進するために用いることも可能である。眼部の血管組織では、視神経乳頭部において、眼動脈が視神経内に入り、網膜中心動脈や後毛様体動脈として、網膜を栄養する血液が送達されている。また、眼球の後方において、眼動脈から短後毛様体動脈へ分岐し、視神経乳頭部で血流を受け、脈絡膜動脈へ至り、網膜の外層を栄養する血液が送達されている。 By using the composition of the present invention, it is possible to increase ocular blood flow, suppress a decrease in ocular blood flow, or maintain ocular blood flow. Since blood flow in the eye can thus be increased, in one embodiment, the present invention can also be used to maintain and promote the health of the vascular tissue in the eye. In the vascular tissue of the eye, the ophthalmic artery enters the optic nerve at the optic disc, and the central retinal artery and posterior ciliary artery deliver blood that nourishes the retina. In addition, at the back of the eyeball, the ophthalmic artery branches into the short posterior ciliary artery, which receives blood flow at the optic nerve head and reaches the choroidal artery, which delivers blood that nourishes the outer layer of the retina.
　眼部においては、上記の血管網が豊富に張り巡らされた部分と、視野の確保の必要上、血管の侵入がない部分とがある。例えば、中心窩を形成する黄斑では、血管の侵入がないため、周囲の網膜血管から栄養成分が浸潤してくる。よって、一つの実施形態において、本発明は、眼部の血管組織の血流量を増加させることにより、血管の侵入のない眼部組織を含め、眼部全体の抗老化に繋がり、健常性を改善及び／又は維持することが可能となる。また、一つの実施形態において、血液の虚血が生じている部分、眼部の血管組織の不調等により、視野狭窄、視野欠損、暗点が生じている場合において、本発明は、眼部の血管組織の血流量を増加させることにより、これらの状態の改善、出現又は拡大を抑制（進行抑制）することが可能となる。 In the eye, there are parts where the above-mentioned vascular network is abundantly spread, and parts where blood vessels do not invade because it is necessary to secure the visual field. For example, in the macula that forms the fovea, there are no blood vessels intruding, so nutritional components infiltrate from the surrounding retinal blood vessels. Accordingly, in one embodiment, the present invention provides anti-aging and improved health of the entire eye, including the eye tissue without vascular invasion, by increasing blood flow in the vascular tissue of the eye. and/or can be maintained. Further, in one embodiment, when visual field narrowing, visual field defect, or scotoma occurs due to blood ischemia, malfunction of the vascular tissue of the eye, etc., the present invention can be applied to the eye. By increasing the blood flow rate of the vascular tissue, it is possible to improve, suppress the appearance or expansion (suppress the progression) of these conditions.
　本発明は、眼部の血管組織の血流量を増加させることにより、血管の侵入のない眼部組織を含め、血液成分を積極的に送達することが可能となる。血管からの血液成分の浸潤が増加すると、組織液の循環も改善することとなる（組織血流の改善）。近年では、眼血流の改善だけでなく、組織液の循環（組織血流）をも改善することの重要性が指摘されており、本明細書において、このような考え方を眼部の全体血流の改善と呼ぶ。後述の実施例（試験例）において、本発明の組成物を、健常ラット、及び、眼血流低下モデルラットに経口により摂取させた場合、視神経乳頭部から放射状に見える網膜中心動脈等の主な血管血流の改善だけでなく、毛細血管や組織液の循環（組織血流）まで改善されており、眼部の全体血流の改善が確認されている。 By increasing the blood flow in the vascular tissue of the eye, the present invention makes it possible to actively deliver blood components, including to the eye tissue without blood vessel invasion. When the infiltration of blood components from blood vessels increases, the circulation of tissue fluid also improves (improvement of tissue blood flow). In recent years, it has been pointed out that it is important to improve not only ocular blood flow but also tissue fluid circulation (tissue blood flow). It is called improvement. In the Examples (Test Examples) described below, when the composition of the present invention was orally ingested by healthy rats and ocular hypoperfusion model rats, major retinal arteries such as the central retinal artery radiating from the optic disc were observed. It has been confirmed that not only vascular blood flow is improved, but also the circulation of capillaries and tissue fluid (tissue blood flow), and that overall blood flow in the eye area is improved.
　近年の眼領域の研究においては、緑内障が眼血管の血流だけでなく、眼組織血流を含めた、眼部の全体血流と関連があることが報告されている。具体的には、緑内障患者においては、眼血流、眼組織血流、及び、眼部の全体血流の全てが、健常者と比較して低下していたことが報告されている（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）。このように、一つの実施形態において、本発明は、眼血流、眼組織血流、及び、眼部の全体血流を増加させることが可能であるため、眼循環障害の治療及び／又は予防用として用いることが可能である。 Recent research in the eye field has reported that glaucoma is related not only to the blood flow in the ocular blood vessels but also to the overall blood flow in the eye, including the eye tissue blood flow. Specifically, it has been reported that in glaucoma patients, ocular blood flow, ocular tissue blood flow, and overall eye blood flow were all reduced compared to healthy subjects (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, the present invention is capable of increasing ocular blood flow, ocular tissue blood flow, and total ocular blood flow, thereby treating and/or preventing ocular circulation disorders. It can be used for any purpose.
　このような眼循環障害としては、緑内障、網膜静脈閉塞症、網膜動脈閉塞症、眼虚血症候群、内頚動脈閉塞症、腎性網膜症、一過性黒内障、又は、加齢黄斑変性等が挙げられる。限定はされないが、眼血流、眼組織血流、及び、眼部の全体血流を増加させる観点から、眼循環障害としては、緑内障、加齢黄斑変性又は、網膜静脈閉塞症が好適である。 Examples of such ocular circulation disorders include glaucoma, retinal vein occlusion, retinal artery occlusion, ocular ischemic syndrome, internal carotid artery occlusion, renal retinopathy, transient amaurosis, and age-related macular degeneration. It will be done. Although not limited to, glaucoma, age-related macular degeneration, or retinal vein occlusion are preferred as the ocular circulation disorder from the viewpoint of increasing ocular blood flow, ocular tissue blood flow, and overall blood flow in the eye. .
　１つの実施態様において、本発明は、眼部の血管組織の血流量を増加させることが確認されているため、例えば、眼部の血液（血）のめぐりを改善したい方や、眼部の血液（血）のめぐりが気になる方、眼部の血液（血）のめぐりを改善することにより、視神経や眼周囲の筋肉の働きを改善したい方、視神経や眼周囲の筋肉の働きが気になる方、眼部の血液（血）のめぐりを改善することにより、眼に血液を届けたい方、眼の健康を支えたい方、視野の欠けが気になる方、視野の狭まりが気になる方、見えにくい方、へも好適に用いることが可能となる。また、１つの実施態様において、本発明は、これらの状態や用途が文言やイラスト等で明記又は想起されるパッケージに封入して、消費者に譲渡することが可能である。 In one embodiment, the present invention has been confirmed to increase blood flow in the vascular tissue of the eye. Those who are concerned about the circulation of blood (blood), those who want to improve the function of the optic nerve and muscles around the eye by improving the circulation of blood (blood) in the eye area, those who are concerned about the function of the optic nerve and muscles around the eye. People who want to deliver blood to their eyes by improving blood circulation in the eye area, people who want to support eye health, people who are concerned about lack of visual field, people who are concerned about narrowing of their visual field. It can also be suitably used for people who have difficulty seeing. Moreover, in one embodiment, the present invention can be enclosed in a package in which these conditions and uses are clearly stated or evoked through words, illustrations, etc., and can be transferred to a consumer.
　上述の通り、眼部では、微細な血管が張り巡らされており、微小な循環（微小循環）が各組織の栄養を担っている。よって、１つの実施態様において、本発明は、眼部の微小循環を改善したい方や、眼部の微小循環が気になる方へも好適に用いることが可能となる。 As mentioned above, the eye region is lined with microscopic blood vessels, and microcirculation (microcirculation) is responsible for nourishing each tissue. Therefore, in one embodiment, the present invention can be suitably used for those who want to improve the microcirculation of the eye and those who are concerned about the microcirculation of the eye.
　本明細書において、予防とは、特定の状態や疾患の発生の防止若しくは遅延、又は、特定の状態や疾患の発生のリスクを低減させることをいう。 As used herein, prevention refers to preventing or delaying the occurrence of a specific condition or disease, or reducing the risk of the occurrence of a specific condition or disease.
　本明細書において、改善とは、特定の状態や疾患の緩和若しくは好転、異常がある状態の悪化の防止若しくは遅延、又は、特定の状態や疾患の進行の防止、遅延、若しくは逆転をいう。 As used herein, improvement refers to alleviation or improvement of a specific condition or disease, prevention or delay of deterioration of an abnormal condition, or prevention, delay, or reversal of the progression of a specific condition or disease.
　本発明の組成物は、食品、飲料、医薬品、飼料、ペットフードに添加又はこれらと混合して使用することができる。または、そのままで飲料又は食品として使用することができる。または眼血流改善、網膜保護、眼部の抗老化、眼部の健常性維持、見え方の改善、血管組織の恒常性維持、眼循環障害のリスク低減又は予防等を機能性としてその旨を明示又は暗示した飲食品、すなわち、健康食品、機能性表示食品、病者用食品及び特定保健用食品として使用することができる。また、上記機能性を明示又は暗示していなくとも、病院及び／又は医院にて、医師から提供されるいわゆるドクターズサプリメントとして使用することができる。 The composition of the present invention can be added to or mixed with foods, drinks, medicines, feeds, and pet foods. Alternatively, it can be used as is as a drink or food. Or, the functions include improving ocular blood flow, protecting the retina, anti-aging of the eye, maintaining the health of the eye, improving vision, maintaining homeostasis of vascular tissue, reducing or preventing the risk of ocular circulation disorders, etc. It can be used explicitly or implicitly as a food or drink, that is, a health food, a food with functional claims, a food for the sick, or a food for specified health uses. Further, even if the above-mentioned functionality is not explicitly stated or implied, it can be used as a so-called doctor's supplement provided by a doctor at a hospital and/or clinic.
　健康食品、機能性表示食品、病者用食品及び特定保健用食品は、具体的には、固形製剤（錠剤、口腔内崩壊錠、顆粒剤、細粒剤、散剤、カプセル剤、チュアブル錠、飴剤など）や液剤（シロップ剤、懸濁剤）、流動食等の各種製剤形態として使用することができる。製剤形態の食品は、公知の医薬製剤と同様に製造することができ、有効成分と、食品として許容できる担体、例えば適当な賦形剤等とを混合した後、慣用の手段を用いて製造することができる。製剤形態としては、限定はされないが、本発明の効果を顕著に奏する観点から、口腔内崩壊錠、チュアブル錠、飴剤、顆粒剤、散剤又は液剤であることが好ましい。 Specifically, health foods, foods with functional claims, foods for the sick, and foods for specified health uses include solid preparations (tablets, orally disintegrating tablets, granules, fine granules, powders, capsules, chewable tablets, and candies). It can be used in various formulations such as liquid preparations (syrups, suspensions), liquid foods, etc. Foods in the form of formulations can be produced in the same manner as known pharmaceutical preparations, and are produced by mixing the active ingredient and a food-acceptable carrier, such as an appropriate excipient, using conventional means. be able to. Although the formulation form is not limited, it is preferably an orally disintegrating tablet, a chewable tablet, a candy, a granule, a powder, or a liquid from the viewpoint of achieving the effects of the present invention.
　例えば、錠剤であれば、粉末状の活性成分と製薬上許容される担体成分（賦形剤など）とを混合して圧縮成形することにより調製でき、キャンディー（飴）などの製菓錠剤は型に注入する方法で調製してもよい。錠剤には、糖衣コーティングを施し、糖衣錠としてもよい。さらに、錠剤は単層錠であってもよく、二層錠などの積層錠であってもよい。 For example, tablets can be prepared by compression molding a mixture of a powdered active ingredient and a pharmaceutically acceptable carrier component (such as an excipient), and confectionery tablets such as candies can be prepared by molding. It may also be prepared by injection. Tablets may be coated with sugar to form sugar-coated tablets. Furthermore, the tablet may be a single-layer tablet or a laminated tablet such as a two-layer tablet.
　顆粒剤などの粉粒剤は、種々の造粒法（押出造粒法、粉砕造粒法、乾式圧密造粒法、流動層造粒法、転動造粒法、高速攪拌造粒法など）により調製してもよく、錠剤は、上記造粒法、打錠法（湿式打錠法、直接打錠法）などを適当に組み合わせて調製できる。 Powder granules such as granules can be produced using various granulation methods (extrusion granulation, pulverization granulation, dry compaction granulation, fluidized bed granulation, rolling granulation, high-speed agitation granulation, etc.) Tablets can be prepared by appropriately combining the above-mentioned granulation method, tableting method (wet tableting method, direct tableting method), etc.
　カプセル剤は、慣用の方法により、カプセル（軟質又は硬質カプセル）内に粉粒剤（粉剤、顆粒剤など）を充填することにより調製できる。 Capsules can be prepared by filling powders (powders, granules, etc.) into capsules (soft or hard capsules) by a conventional method.
　液剤は、各成分を担体成分である水性媒体（精製水、エタノール含有精製水など）に溶解又は分散させ、必要により濾過又は滅菌処理し、所定の容器に充填し、滅菌処理することにより調製できる。本発明の固形製剤の好ましい剤形は、カプセル剤又は錠剤であり、軟質カプセル（軟カプセル剤、ソフトカプセル）であることがより好ましい。 Liquid preparations can be prepared by dissolving or dispersing each component in an aqueous medium (purified water, ethanol-containing purified water, etc.) as a carrier component, filtering or sterilizing it if necessary, filling it into a designated container, and sterilizing it. . A preferred dosage form of the solid preparation of the present invention is a capsule or a tablet, and more preferably a soft capsule.
　軟カプセル剤は表面が滑らかで飲み込みやすく、使用者に好まれる。一般的な軟カプセル剤の製造方法として、平板式、ロータリー方式、シームレス方式が例示される。 Soft capsules have a smooth surface and are easy to swallow, making them preferred by users. Examples of common methods for producing soft capsules include a flat plate method, a rotary method, and a seamless method.
　ロータリー方式（打ち抜き法）の製造は、シート状カプセル皮膜が、流動する充填内容物を挟み込み、回転する円筒型の金型の穴に沿ってカプセル形状に形成する。一方で、シームレス方式（滴下法）の製造は、同心円の多重ノズルからカプセル皮膜組成物と内容物が同時に吐出され、継ぎ目の無いカプセル形状に形成される。 In manufacturing using the rotary method (punching method), a sheet-like capsule film sandwiches the flowing filling contents and forms a capsule shape along the holes of a rotating cylindrical mold. On the other hand, in the seamless method (dropping method), the capsule coating composition and the contents are simultaneously discharged from multiple concentric nozzles, forming a seamless capsule shape.
　軟カプセル剤の皮膜の基剤は、特に限定はされないが、デンプン、プルラン、セルロース、ポリビニルアルコール、ゼラチン、コハク化ゼラチン等を用いることができ、デンプン、ゼラチン、コハク化ゼラチンが好ましく、ゼラチン、コハク化ゼラチンが更に好ましい。これらは単独で又は二種以上組み合わせて使用してもよい。 The base material for the film of the soft capsule is not particularly limited, but starch, pullulan, cellulose, polyvinyl alcohol, gelatin, succinated gelatin, etc. can be used, and starch, gelatin, and succinated gelatin are preferred, and gelatin, succinated gelatin, etc. Further preferred is gelatin. These may be used alone or in combination of two or more.
　また、スープ類、ジュース類、果汁飲料、牛乳、乳飲料、乳清飲料、乳酸菌飲料、茶飲料、アルコール飲料、コーヒー飲料、炭酸飲料、清涼飲料水、水飲料、ココア飲料、ゼリー状飲料、スポーツ飲料、ダイエット飲料等の液状飲料、プリン、ヨーグルトなどの半固形食品、麺類、菓子類、スプレッド類等として、本発明の組成物を製造することができる。 Also, soups, juices, fruit juice drinks, milk, milk drinks, whey drinks, lactic acid bacteria drinks, tea drinks, alcoholic drinks, coffee drinks, carbonated drinks, soft drinks, water drinks, cocoa drinks, jelly drinks, sports drinks. The composition of the present invention can be produced as beverages, liquid drinks such as diet drinks, semi-solid foods such as puddings and yogurt, noodles, confectionery, spreads, and the like.
　本発明の組成物を食品組成物として調製する場合は、種々の食品添加物を配合してもよい。食品添加物としては、例えば、酸化防止剤、色素、香料、調味料、甘味料、酸味料、pH調整剤、品質安定剤、保存剤等が挙げられる。 When preparing the composition of the present invention as a food composition, various food additives may be added. Examples of food additives include antioxidants, pigments, fragrances, seasonings, sweeteners, acidulants, pH adjusters, quality stabilizers, preservatives, and the like.
　本発明の組成物を医薬組成物として調製する場合は、有効成分である、ショウガ及び／又はその抽出物と、好ましくは薬学的に許容される担体を含む製剤として調製する。薬学的に許容される担体とは、一般的に、前記有効成分とは反応しない、不活性の、無毒の、固体若しくは液体の、増量剤、希釈剤又はカプセル化材料等をいい、例えば、水、エタノール、ポリオール類、適切なそれらの混合物、植物性油等の溶媒又は分散媒体等が挙げられる。 When the composition of the present invention is prepared as a pharmaceutical composition, it is prepared as a preparation containing the active ingredient, ginger and/or an extract thereof, and preferably a pharmaceutically acceptable carrier. A pharmaceutically acceptable carrier generally refers to an inert, non-toxic, solid or liquid filler, diluent, or encapsulating material that does not react with the active ingredient, such as water. , ethanol, polyols, appropriate mixtures thereof, solvents or dispersion media such as vegetable oils, and the like.
　医薬組成物は、経口により、非経口により、例えば、口腔内に、消化管内に、又は鼻腔内に投与される。経口投与製剤としては、固形製剤（錠剤、口腔内崩壊錠、顆粒剤、細粒剤、散剤、カプセル剤、チュアブル錠、飴剤など）や、液剤（シロップ剤、懸濁剤、吸入剤）等が挙げられる。非経口投与製剤としては、点眼剤、点滴剤、点鼻剤及び注射剤等が挙げられる。製剤形態としては、限定はされないが、本発明の効果を顕著に奏する観点から、口腔内崩壊錠、チュアブル錠、飴剤、顆粒剤、散剤又は液剤であることが好ましい。 The pharmaceutical composition is administered orally, parenterally, for example, into the oral cavity, into the gastrointestinal tract, or into the nasal cavity. Orally administered preparations include solid preparations (tablets, orally disintegrating tablets, granules, fine granules, powders, capsules, chewable tablets, lozenges, etc.) and liquid preparations (syrups, suspensions, inhalants), etc. can be mentioned. Examples of parenteral preparations include eye drops, drops, nasal drops, and injections. Although the formulation form is not limited, it is preferably an orally disintegrating tablet, a chewable tablet, a candy, a granule, a powder, or a liquid from the viewpoint of achieving the effects of the present invention.
　医薬組成物は、さらに医薬分野において慣用されている添加剤を含んでいてもよい。そのような添加剤には、例えば、賦形剤、結合剤、崩壊剤、滑沢剤、抗酸化剤、着色剤、矯味剤等があり、必要に応じて適宜使用できる。長時間作用できるように徐放化するため、既知の遅延剤等でコーティングすることもできる。医薬組成物は、さらに必要に応じてその他の添加剤や薬剤、例えば制酸剤、胃粘膜保護剤を加えてもよい。 The pharmaceutical composition may further contain additives commonly used in the pharmaceutical field. Such additives include, for example, excipients, binders, disintegrants, lubricants, antioxidants, coloring agents, and flavoring agents, which can be used as appropriate. In order to achieve sustained release so that it can act over a long period of time, it can also be coated with a known retardant. The pharmaceutical composition may further contain other additives and drugs, such as antacids and gastric mucosal protectants, if necessary.
　医薬組成物は、口腔用組成物、内服組成物などの形態で適用することができる。また医薬組成物を治療的に使用してもよいし、非治療的に使用してもよい。 The pharmaceutical composition can be applied in the form of an oral composition, an internal composition, or the like. The pharmaceutical compositions may also be used therapeutically or non-therapeutically.
　ショウガ及び／又はその抽出物の成人１日あたりの経口による摂取量又は投与量は、個体の状態、体重、性別、年齢、素材の活性、摂取又は投与経路、摂取又は投与スケジュール、製剤形態又はその他の要因により適宜決定することができる。ショウガ及び／又はその抽出物の成人１日あたりの経口による摂取量又は投与量は、例えば、０．０１ｍｇ／ｋｇ体重／日以上が好ましく、０．０２ｍｇ／ｋｇ体重／日以上がより好ましく、０．０５ｍｇ／ｋｇ体重／日以上が更に好ましく、０．１ｍｇ／ｋｇ体重／日以上が特に好ましい。ショウガ及び／又はその抽出物の成人１日あたりの経口による摂取量又は投与量は、例えば、１０ｍｇ／ｋｇ体重／日以下が好ましく、５ｍｇ／ｋｇ体重／日以下がより好ましく、２ｍｇ／ｋｇ体重／日以下が更に好ましく、１ｍｇ／ｋｇ体重／日以下が特に好ましい。ショウガ及び／又はその抽出物の成人１日あたりの経口による摂取量又は投与量は、例えば、０．０１～１０ｍｇ／ｋｇ体重／日が好ましく、０．０２～５ｍｇ／ｋｇ体重／日がより好ましく、０．０５～２ｍｇ／ｋｇ体重／日が更に好ましく、０．１～１ｍｇ／ｋｇ体重／日が特に好ましい。ショウガ及び／又はその抽出物の含有量は、上記の摂取量又は投与量となる量とすることができる。 The daily oral intake or dosage of ginger and/or its extract for adults depends on the condition of the individual, body weight, sex, age, activity of the material, route of intake or administration, schedule of intake or administration, formulation form, and other factors. It can be determined as appropriate depending on the following factors. The daily oral intake or dosage of ginger and/or its 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, and 0.01 mg/kg body weight/day or more, for example. More preferably .05 mg/kg body weight/day or more, particularly preferably 0.1 mg/kg body weight/day or more. The daily oral intake or dosage of ginger and/or its 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, and 2 mg/kg body weight/day. More preferably, the amount is less than 1 mg/kg body weight/day, particularly preferably less than 1 mg/kg body weight/day. The daily oral intake or dosage of ginger and/or its extract for adults is, for example, preferably 0.01 to 10 mg/kg body weight/day, more preferably 0.02 to 5 mg/kg body weight/day. , 0.05 to 2 mg/kg body weight/day is more preferred, and 0.1 to 1 mg/kg body weight/day is particularly preferred. The content of ginger and/or its extract can be set to the above-mentioned intake or administration amount.
　また、一つの実施態様において、ショウガ抽出物の成人１日あたりの経口による摂取量又は投与量は、例えば、０．５ｍｇ／日以上が好ましく、１ｍｇ／日以上がより好ましく、３ｍｇ／日以上が更に好ましく、５ｍｇ／日以上が特に好ましく、１０ｍｇ／日以上が最も好ましい。ショウガ抽出物の成人１日あたりの経口による摂取量又は投与量は、例えば、５００ｍｇ／日以下が好ましく、２００ｍｇ／日以下がより好ましく、１００ｍｇ／日以下が更に好ましく、５０ｍｇ／日以下が特に好ましい。ショウガ抽出物の成人１日あたりの経口による摂取量又は投与量は、例えば、０．５～５００ｍｇ／日以下が好ましく、１～２００ｍｇ／日以下がより好ましく、３～１００ｍｇ／日以下が更に好ましく、５～５０ｍｇ／日以下が特に好ましい。 In one embodiment, the daily oral intake or dosage of ginger extract for adults is, for example, preferably 0.5 mg/day or more, more preferably 1 mg/day or more, and 3 mg/day or more. More preferably, 5 mg/day or more is particularly preferred, and 10 mg/day or more is most preferred. The daily oral intake or dosage of ginger extract for adults is, for example, preferably 500 mg/day or less, more preferably 200 mg/day or less, even more preferably 100 mg/day or less, particularly preferably 50 mg/day or less. . The daily oral intake or dosage of ginger extract for adults is, for example, preferably 0.5 to 500 mg/day, more preferably 1 to 200 mg/day, even more preferably 3 to 100 mg/day. , 5 to 50 mg/day or less is particularly preferred.
　また、一つの実施態様において、ショウガの成人１日あたりの経口による摂取量又は投与量は、例えば、２０ｍｇ／日以上が好ましく、４０ｍｇ／日以上がより好ましく、１２０ｍｇ／日以上が更に好ましく、２００ｍｇ／日以上が特に好ましく、４００ｍｇ／日以上が最も好ましい。ショウガの成人１日あたりの経口による摂取量又は投与量は、例えば、５０００ｍｇ／日以下が好ましく、３０００ｍｇ／日以下がより好ましく、１０００ｍｇ／日以下が更に好ましく、８００ｍｇ／日以下が特に好ましい。ショウガの経口による摂取量又は投与量は、例えば、２０～５０００ｍｇ／日以下が好ましく、４０～３０００ｍｇ／日以下がより好ましく、１２０～１０００ｍｇ／日以下が更に好ましく、２００～８００ｍｇ／日以下が特に好ましい。 In one embodiment, the daily oral intake or dosage of ginger for adults is, for example, preferably 20 mg/day or more, more preferably 40 mg/day or more, even more preferably 120 mg/day or more, and 200 mg/day or more. /day or more is particularly preferred, and 400 mg/day or more is most preferred. The daily oral intake or dosage of ginger for adults is, for example, preferably 5000 mg/day or less, more preferably 3000 mg/day or less, even more preferably 1000 mg/day or less, and particularly preferably 800 mg/day or less. The oral intake or dosage of ginger is, for example, preferably 20 to 5000 mg/day or less, more preferably 40 to 3000 mg/day, even more preferably 120 to 1000 mg/day, particularly 200 to 800 mg/day. preferable.
　動物への投与量を人の投与量に換算する場合、限定はされないが、例えば、動物での有効量を体重ｋｇ当たりの投与量としてヒト投与量に換算し、その１／６０以下とする、という方法を用いることができる。すなわち、動物での有効量がＸｍｇ／ｋｇであれば、ヒトでの投与量（ｍｇ／日）は、Ｘ（ｍｇ）×体重（ｋｇ）／６０～６００などといった形で計算することができる。一つの実施態様において、ショウガ及び／又はその抽出物の成人１日あたりの経口による摂取量又は投与量は、例えば、１ｍｇ／日以上、２ｍｇ／日以上、３ｍｇ／日以上、４ｍｇ／日以上、５ｍｇ／日以上、６ｍｇ／日以上、７ｍｇ／日以上、８ｍｇ／日以上、９ｍｇ／日以上、１０ｍｇ／日以上とすることができ、１０００ｍｇ／日以下、９００ｍｇ／日以下、８００ｍｇ／日以下、７００ｍｇ／日以下、６００ｍｇ／日以下、５００ｍｇ／日以下、４００ｍｇ／日以下、３００ｍｇ／日以下、２００ｍｇ／日以下、１５０ｍｇ／日以下、１００ｍｇ／日以下、７５ｍｇ／日以下、５０ｍｇ／日以下、３０ｍｇ／日以下、２０ｍｇ／日以下、１０ｍｇ／日以下とすることもできる。 When converting the dose for animals to the dose for humans, there are no limitations, but for example, the effective dose for animals is converted to the human dose as the dose per kg of body weight, and the dose is 1/60 or less. This method can be used. That is, if the effective dose for animals is X mg/kg, the dose for humans (mg/day) can be calculated as follows: X (mg) x body weight (kg)/60-600. In one embodiment, the daily oral intake or dosage of ginger and/or its extract for adults is, 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, 10 mg/day or more, and 1000 mg/day or less, 900 mg/day or less, 800 mg/day or less, 700 mg/day or less, 600 mg/day or less, 500 mg/day or less, 400 mg/day or less, 300 mg/day or less, 200 mg/day or less, 150 mg/day or less, 100 mg/day or less, 75 mg/day or less, 50 mg/day or less, It can also be 30 mg/day or less, 20 mg/day or less, or 10 mg/day or less.
　なお、成人１日あたりの経口による摂取量又は投与量は、剤形に合わせて、例えばカプセル剤であれば、１～６カプセル、１～４カプセル、１～３カプセル、又は１～２カプセルに分けて服用してもよい。 In addition, the oral intake or dosage per day for adults is 1 to 6 capsules, 1 to 4 capsules, 1 to 3 capsules, or 1 to 2 capsules depending on the dosage form. May be taken separately.
　本発明の組成物は、１日１回～数回に分け、通常、１日１～６回、１日１～３回、１日１～２回又は任意の期間及び間隔で摂取若しくは投与され得るが、１日１回が好ましい。 The composition of the present invention is divided into once to several times a day, usually taken or administered 1 to 6 times a day, 1 to 3 times a day, 1 to 2 times a day, or at any period and interval. However, once a day is preferred.
　本発明は、以下の態様でもあり得る。
　ショウガ及び／又はその抽出物を含有する、眼血流の改善及び／又は維持用組成物；
　ショウガ及び／又はその抽出物を含有する、眼部の血管組織の健常性維持用組成物；
　ショウガ及び／又はその抽出物を含有する、眼部の抗老化用組成物；
　ショウガ及び／又はその抽出物を含有する、眼部の健常性、視野狭窄、視野欠損、若しくは暗点の出現又は拡大の改善及び／又は維持用の組成物；
　ショウガ及び／又はその抽出物を含有する、眼循環障害の治療及び／又は予防用の組成物；
　眼血流の改善及び／又は維持における使用のための、ショウガ及び／又はその抽出物を含有する組成物；
　眼部の血管組織の健常性維持における使用のための、ショウガ及び／又はその抽出物を含有する組成物；
　眼部の抗老化における使用のための、ショウガ及び／又はその抽出物を含有する組成物；
　眼部の健常性、視野狭窄、視野欠損、若しくは暗点の出現又は拡大の改善及び／又は維持における使用のための、ショウガ及び／又はその抽出物を含有する組成物；
　眼循環障害の治療及び／又は予防における使用のための、ショウガ及び／又はその抽出物を含有する組成物；
　ショウガ及び／又はその抽出物の、眼血流の改善及び／又は維持剤の製造のための使用；
　ショウガ及び／又はその抽出物の、眼部の血管組織の健常性維持剤の製造のための使用；
　ショウガ及び／又はその抽出物の、眼部の抗老化剤の製造のための使用；
　ショウガ及び／又はその抽出物の、眼部の健常性、視野狭窄、視野欠損、若しくは暗点の出現又は拡大の改善及び／又は維持剤の製造のための使用；
　ショウガ及び／又はその抽出物の、眼循環障害の治療及び／又は予防剤の製造のための使用；
　ショウガ及び／又はその抽出物を含有する組成物を、人に摂取させることを含む、眼血流の改善及び／又は維持方法；
　ショウガ及び／又はその抽出物を含有する組成物を、人に摂取させることを含む、眼部の血管組織の健常性維持方法；
　ショウガ及び／又はその抽出物を含有する組成物を、人に摂取させることを含む、眼部の抗老化方法；
　ショウガ及び／又はその抽出物を含有する組成物を、人に摂取させることを含む、眼部の健常性、視野狭窄、視野欠損、若しくは暗点の出現又は拡大の改善及び／又は維持方法；
　ショウガ及び／又はその抽出物を含有する組成物を、人に摂取させることを含む、眼循環障害の治療及び／又は予防方法；
　前記眼循環障害が、緑内障、網膜静脈閉塞症、網膜動脈閉塞症、眼虚血症候群、内頚動脈閉塞症、腎性網膜症、一過性黒内障、加齢黄斑変性である、上記組成物、使用、又は方法；
　医薬品又は飲食品である、上記組成物；
　剤形が、口腔内崩壊錠、チュアブル錠、飴剤、顆粒剤、散剤又は液剤である、上記組成物、使用、又は方法；
　前記ショウガが、アカショウガである、上記組成物、使用、又は方法；
　前記ショウガ及び／又はその抽出物が、アカショウガ及び／又はその抽出物である、上記組成物、使用、又は方法；
　前記ショウガの部位が、根茎を含む、上記組成物、使用、又は方法；
　前記ショウガ抽出物における抽出溶媒が、含水エタノールである、上記組成物、使用、又は方法；
　アカショウガにおける［６］－ｇｉｎｇｅｒｏｌおよび［６］－ｓｈｏｇａｏｌの総含有量が、３．０質量％以上である、上記組成物、使用、又は方法；
　アカショウガにおける［６］－ｇｉｎｇｅｒｏｌおよび［６］－ｓｈｏｇａｏｌの総含有量が、６．０質量％以上である、上記組成物、使用、又は方法；
　アカショウガにおけるタンニンの含有量が、プロシアニジンＢ２換算で０．５質量％以上である、上記組成物、使用、又は方法；
　アカショウガにおけるタンニンの含有量が、プロシアニジンＢ２換算で１．５質量％以上である、上記組成物、使用、又は方法；
　ショウガ抽出物の含有量が、０．０１～９５質量％である、上記組成物、使用、又は方法；
　ショウガ抽出物の含有量が、０．０５～７０質量％である、上記組成物、使用、又は方法；
　ショウガ抽出物の含有量が、０．１～５０質量％である、上記組成物、使用、又は方法；
　ショウガ抽出物の含有量が、０．５～３０質量％である、上記組成物、使用、又は方法；
　ショウガの含有量が、０．１～９９質量％である、上記組成物、使用、又は方法；
　ショウガの含有量が、０．５～９５質量％である、上記組成物、使用、又は方法；
　ショウガの含有量が、１～９０質量％である、上記組成物、使用、又は方法；
　ショウガの含有量が、３～８０質量％である、上記組成物、使用、又は方法；
　ショウガ及び／又はその抽出物の１日あたりの経口による摂取量が、０．５～５００ｍｇである、上記組成物、使用、又は方法；
　ショウガ及び／又はその抽出物の１日あたりの経口による摂取量が、１～２００ｍｇである、上記組成物、使用、又は方法；
　ショウガ及び／又はその抽出物の１日あたりの経口による摂取量が、３～１００ｍｇである、上記組成物、使用、又は方法；
　ショウガ及び／又はその抽出物の１日あたりの経口による摂取量が、５～５０ｍｇである、上記組成物、使用、又は方法；
　ショウガの１日あたりの経口による摂取量が、２０～５０００ｍｇである、上記組成物、使用、又は方法；
　ショウガの１日あたりの経口による摂取量が、４０～３０００ｍｇである、上記組成物、使用、又は方法；
　ショウガの１日あたりの経口による摂取量が、１２０～１０００ｍｇである、上記組成物、使用、又は方法；
　ショウガの１日あたりの経口による摂取量が、２００～８００ｍｇである、上記組成物、使用、又は方法；
　眼血流が、網膜及び／又は脈絡膜の血流である、上記組成物、使用、又は方法；
　眼血流が、眼組織血流を含む、上記組成物、使用、又は方法； The present invention may also have the following aspects.
A composition for improving and/or maintaining ocular blood flow, containing ginger and/or an extract thereof;
A composition for maintaining the health of vascular tissue in the eye, containing ginger and/or an extract thereof;
An anti-aging composition for the eye region containing ginger and/or an extract thereof;
A composition for improving and/or maintaining ocular health, visual field constriction, visual field defect, or the appearance or expansion of a scotoma, containing ginger and/or an extract thereof;
A composition for the treatment and/or prevention of ocular circulation disorders, containing ginger and/or an extract thereof;
Compositions containing ginger and/or extracts thereof for use in improving and/or maintaining ocular blood flow;
A composition containing ginger and/or an extract thereof for use in maintaining the health of vascular tissue of the eye;
Compositions containing ginger and/or extracts thereof for use in anti-aging of the eye;
Compositions containing ginger and/or extracts thereof for use in improving and/or maintaining ocular health, visual field constriction, visual field defects, or the appearance or enlargement of scotoma;
Compositions containing ginger and/or extracts thereof for use in the treatment and/or prevention of ocular circulation disorders;
Use of ginger and/or its extract for the production of an agent for improving and/or maintaining ocular blood flow;
Use of ginger and/or its extract for the production of an agent for maintaining the health of vascular tissue in the eye;
Use of ginger and/or its extract for the manufacture of an anti-aging agent for the eye;
Use of ginger and/or its extract for the production of an agent for improving and/or maintaining ocular health, visual field constriction, visual field defect, or appearance or expansion of scotoma;
Use of ginger and/or its extract for the production of a therapeutic and/or preventive agent for ocular circulation disorders;
A method for improving and/or maintaining ocular blood flow, which comprises causing a person to ingest a composition containing ginger and/or an extract thereof;
A method for maintaining the health of vascular tissue in the eye region, which comprises causing a person to ingest a composition containing ginger and/or an extract thereof;
An anti-aging method for the eye region, the method comprising causing a person to ingest a composition containing ginger and/or an extract thereof;
A method for improving and/or maintaining ocular health, visual field narrowing, visual field defect, or the appearance or expansion of a scotoma, the method comprising causing a person to ingest a composition containing ginger and/or an extract thereof;
A method for treating and/or preventing ocular circulation disorders, the method comprising causing a person to ingest a composition containing ginger and/or an extract thereof;
The above composition and use, wherein the ocular circulation disorder is glaucoma, retinal vein occlusion, retinal artery occlusion, ocular ischemia syndrome, internal carotid artery occlusion, renal retinopathy, transient amaurosis, age-related macular degeneration. , or method;
The above composition, which is a pharmaceutical product or a food or drink product;
The above composition, use, or method, wherein the dosage form is an orally disintegrating tablet, a chewable tablet, a lozenge, a granule, a powder, or a liquid;
The above composition, use, or method, wherein the ginger is red ginger;
The above composition, use, or method, wherein the ginger and/or extract thereof is red ginger and/or an extract thereof;
The above composition, use, or method, wherein the ginger part comprises a rhizome;
The above composition, use, or method, wherein the extraction solvent in the ginger extract is aqueous ethanol;
The above 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 above composition, use, or method, wherein the total content of [6]-gingerol and [6]-shogaol in red ginger is 6.0% by mass or more;
The above composition, use, or method, wherein the tannin content in red ginger is 0.5% by mass or more in terms of procyanidin B2;
The above composition, use, or method, wherein the tannin content in red ginger is 1.5% by mass or more in terms of procyanidin B2;
The above composition, use, or method, wherein the content of ginger extract is 0.01 to 95% by mass;
The above composition, use, or method, wherein the content of ginger extract is 0.05 to 70% by mass;
The above composition, use, or method, wherein the content of ginger extract is 0.1 to 50% by mass;
The above composition, use, or method, wherein the content of ginger extract is 0.5 to 30% by mass;
The above composition, use, or method, wherein the content of ginger is 0.1 to 99% by mass;
The above composition, use, or method, wherein the content of ginger is 0.5 to 95% by mass;
The above composition, use, or method, wherein the content of ginger is 1 to 90% by mass;
The above composition, use, or method, wherein the content of ginger is 3 to 80% by mass;
The above composition, use, or method, wherein the daily oral intake of ginger and/or its extract is 0.5 to 500 mg;
The above composition, use, or method, wherein the daily oral intake of ginger and/or its extract is 1 to 200 mg;
The above composition, use, or method, wherein the daily oral intake of ginger and/or its extract is 3 to 100 mg;
The above composition, use, or method, wherein the daily oral intake of ginger and/or its extract is 5 to 50 mg;
The above composition, use, or method, wherein the daily oral intake of ginger is 20 to 5000 mg;
The above composition, use, or method, wherein the daily oral intake of ginger is 40 to 3000 mg;
The above composition, use, or method, wherein the daily oral intake of ginger is 120 to 1000 mg;
The above composition, use, or method, wherein the daily oral intake of ginger is 200 to 800 mg;
The above composition, use, or method, wherein the ocular blood flow is retinal and/or choroidal blood flow;
The above compositions, uses, or methods, wherein the ocular blood flow comprises ocular tissue blood flow;
　次に、実施例により本発明を具体的に説明するが、本発明は以下の実施例に限定されるものではない。また、実施例において示すエキスの量は、特に明示がない限り、乾燥固形分換算と賦形剤等を含んだ量を示す。 Next, the present invention will be specifically explained with reference to Examples, but the present invention is not limited to the following Examples. In addition, unless otherwise specified, the amount of extract shown in the Examples is the amount calculated in terms of dry solid content and including excipients and the like.
　［試験例１．ヒト網膜毛細血管内皮細胞における眼血流評価試験］
　ヒト網膜毛細血管内皮細胞にショウガを添加した時の、血管を拡張させる一酸化窒素（ＮＯ）の合成酵素の活性化作用を評価した。
　ＨＲＭＥＣ（ヒト網膜毛細血管内皮細胞）を６ｗｅｌｌプレートにそれぞれ３×１０５個／ｍＬで播種し、０．５％ジメチルスルホキシド（ＤＭＳＯ）で希釈したアカショウガエキス（赤ショウガエキス－Ｐ、オリザ油化株式会社製、図中では「Ｏ－２」と表記、以下同じ）０．００１％を添加して３７℃で３０分培養した。７．５％アクリルアミドゲルを用いたＳＤＳ－ＰＡＧＥにより細胞由来タンパク液２５μｇ／ｌａｎｅを分離し、Ｔｗ－ＰＢＳで調整した１％スキムミルクにてブロッキングした後、１０００倍希釈抗Ｐ－ｅＮＯＳ抗体（Ｓｅｒ１１７７、Ｃｅｌｌ　Ｓｉｇｎａｌｉｎｇ　Ｔｅｃｈｎｏｌｏｇｙ，Ｉｎｃ．＃９７１５）、５０００倍希釈抗ｅＮＯＳ抗体（ｔｏｔａｌ、Ｃｅｌｌ　Ｓｉｇｎａｌｉｎｇ　Ｔｅｃｈｎｏｌｏｇｙ，Ｉｎｃ．＃３２０３７）を加え、室温で１時間インキュベートした後、５０００倍希釈ヤギ抗ウサギＩｇＧ－ＨＲＰ（Ｓｉｇｍａ，＃Ａ０５４５）で室温で１時間インキュベートした。その後、ＥＣＬ　ｐｒｉｍｅで発光させＧｅｌ　ｄｏｇ(Ｂｉｏ－Ｒａｄ　Ｌａｂｏｒａｔｏｒｉｅｓ，Ｉｎｃ．)でシグナルを検出した。Ｐ－ｅＮＯＳ／ｅ－ＮＯＳを求め、赤ショウガエキスを加えないときを１として比較した。 [Test Example 1. Ocular blood flow evaluation test in human retinal capillary endothelial cells]
When ginger was added to human retinal capillary endothelial cells, the activation effect of nitric oxide (NO) synthase, which dilates blood vessels, was evaluated.
HRMEC (human retinal capillary endothelial cells) were seeded in 6-well plates at 3 x 10 5 cells/mL, and red ginger extract (red ginger extract-P, Oryza oil-based) diluted with 0.5% dimethyl sulfoxide (DMSO). Co., Ltd., indicated as "O-2" in the figure, the same applies hereinafter) was added at 0.001% and cultured at 37°C for 30 minutes. 25 μg/lane of cell-derived protein solution was separated by SDS-PAGE using 7.5% acrylamide gel, blocked with 1% skim milk adjusted with Tw-PBS, and then treated with 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 after incubation for 1 hour at room temperature, 5000-fold diluted goat anti-rabbit IgG-HRP (S igma , #A0545) for 1 hour at room temperature. Thereafter, light was emitted using ECL prime, and the signal was detected using Gel dog (Bio-Rad Laboratories, Inc.). P-eNOS/e-NOS was determined and compared with the value when no red ginger extract was added as 1.
Figure JPOXMLDOC01-appb-T000001
Figure JPOXMLDOC01-appb-T000001
　結果を表１に示す。ヒト網膜毛細血管内皮細胞に、ショウガエキスを添加することにより、血管を拡張させる一酸化窒素（ＮＯ）の合成酵素の活性化（Ｐ－ｅＮＯＳ／ｅ－ＮＯＳ値の増加）が確認された。このことから、ショウガが後眼部の血流改善に有効であることが示唆された。 The results are shown in Table 1. By adding ginger extract to human retinal capillary endothelial cells, activation of nitric oxide (NO) synthase, which dilates blood vessels (increase in P-eNOS/e-NOS values), was confirmed. This suggests that ginger is effective in improving blood flow in the posterior segment of the eye.
　［試験例２：正常ラットにおける眼血流評価試験］
　経口（舌下）投与による眼血流への影響を評価するため、健常ラットを用いて眼の視神経乳頭周囲の血流量の変化を測定した。
　健常ラット（Brown Norway、雄、８-１２週齢、SLC社製、体重約２００ｇ、以下同じ）におけるベースラインとなる眼血流量をレーザースペックルフローグラフィー（ＬＳＦＧ－ＮＡＶＩ、ソフトケア有限会社製）及び付属の解析アプリケーション（ＬＳＦＧ　ａｎａｌｙｚｅｒ）を用いて測定した。当該測定法によると、散瞳剤や造影剤を使わずに非侵襲、又は低侵襲にて眼血流量をリアルタイムに測定、解析することが可能である。 [Test Example 2: Ocular blood flow evaluation test in normal rats]
To evaluate the effect of oral (sublingual) administration on ocular blood flow, changes in blood flow around the optic disc of the eye were measured using healthy rats.
Baseline ocular blood flow in healthy rats (Brown Norway, male, 8-12 weeks old, manufactured by SLC, weight approximately 200 g, same hereinafter) was measured using laser speckle flowgraphy (LSFG-NAVI, manufactured by Softcare Co., Ltd.) and was measured using the attached analysis application (LSFG analyzer). According to this measurement method, it is possible to measure and analyze ocular blood flow in real time in a non-invasive or minimally invasive manner without using mydriatic agents or contrast agents.
　ベースラインとなる眼血流量の測定１週間後に、被験試料としてアカショウガエキス粉末（赤ショウガエキス－Ｐ、オリザ油化株式会社製、図中では「Ｏ－２」と表記、以下同じ）を２５ｍｇ、又は５０ｍｇにて舌下投与し、１０分後に麻酔を施し、その３０分後に、再度レーザースペックルフローグラフィーにより眼血流量の指標であるＭＢＲ値を測定した。ベースラインとなる眼血流量と、被験試料摂取後の眼血流量の測定結果を図１に示す。なお、各投与群でラットを８匹ずつ用い、Ｈｏｌｍ－Ｓｉｄａｋ検定により統計処理を行った。また、図中のＡｖｅＡＬＬ（Ｖ）は、血管領域の血流量（ＭＢＲ平均値、以下同じ）を示す。 One week after measuring the baseline ocular blood flow, 25 mg of red ginger extract powder (red ginger extract-P, manufactured by Oryza Yuka Co., Ltd., indicated as "O-2" in the figure, the same hereinafter) was administered as a test sample. Or 50 mg was administered sublingually, anesthesia was administered 10 minutes later, and 30 minutes later, the MBR value, which is an index of ocular blood flow, was measured again by laser speckle flowgraphy. Figure 1 shows the measurement results of the baseline ocular blood flow and the ocular blood flow after ingestion of the test sample. In addition, eight rats were used in each administration group, and statistical processing was performed using the Holm-Sidak test. Further, AveALL (V) in the figure indicates the blood flow rate (MBR average value, the same applies hereinafter) in the blood vessel region.
　図１に示す通り、ショウガ（アカショウガエキス）を投与した場合、健常のラットにおいて、眼血流量の増加が認められた。この眼血流量の増加作用は、ショウガの摂取量に依存して高まることが確認された。 As shown in Figure 1, when ginger (red ginger extract) was administered, an increase in ocular blood flow was observed in healthy rats. It was confirmed that this effect of increasing ocular blood flow increased depending on the amount of ginger ingested.
　［試験例３：眼血流低下型ラットにおける眼血流評価試験］
　（３－１．眼血流低下型モデルの検討）
　健常ラット（Brown Norway、雄、８-１２週齢、SLC社製）に麻酔を施し、１０分後にエンドセリン－１（図中では「ＥＴ１」と表記、以下同じ）を、投与無し（コントロール群）、１．２５ｐｍｏｌ、２．５ｐｍｏｌ、又は５．０ｐｍｏｌにて硝子体内注射し、２０分後に、レーザースペックルフローグラフィーにより眼血流量（ＡｖｅＡＬＬ（Ａ）：全領域の血流量）を測定した。それぞれの測定結果における後眼部血流マップを図２、及び、解析後のグラフを図３に示す。Ｔｕｒｋｅｙ－Ｋｒａｍｅｒ検定により統計処理を行った。 [Test Example 3: Ocular blood flow evaluation test in rats with reduced ocular blood flow]
(3-1. Examination of ocular blood flow reduction type model)
Healthy rats (Brown Norway, male, 8-12 weeks old, manufactured by SLC) were anesthetized, and 10 minutes later, endothelin-1 (indicated as "ET1" in the figure, the same hereinafter) was administered without administration (control group). , 1.25 pmol, 2.5 pmol, or 5.0 pmol was injected intravitreally, and 20 minutes later, the ocular blood flow (AveALL (A): blood flow in the entire area) was measured by laser speckle flowgraphy. The posterior segment blood flow map for each measurement result is shown in FIG. 2, and the graph after analysis is shown in FIG. 3. Statistical processing was performed using the Turkey-Kramer test.
　図２及び図３に示す通り、エンドセリン－１（ＥＴ－１）の投与により、眼血流量（全領域の血流量）が低下することが認められた。エンドセリン－１を２．５ｐｍｏｌで硝子体内投与した群では、コントロール群に対して有意に眼血流量が低下することが確認された。よって、以下の試験例では、眼血流低下型モデルとして、エンドセリン－１を２．５ｐｍｏｌで硝子体内投与することによる眼血流低下型モデルを用いた。 As shown in FIGS. 2 and 3, it was observed that the ocular blood flow (blood flow in all regions) was reduced by administration of endothelin-1 (ET-1). In the group in which 2.5 pmol of endothelin-1 was administered intravitreally, it was confirmed that the ocular blood flow was significantly lower than in the control group. Therefore, in the following test examples, an ocular blood flow reduction model was used in which 2.5 pmol of endothelin-1 was administered intravitreally.
　（３－２．眼血流低下型ラットにおける眼血流評価試験）
　（被験試料の内服群）
　健常ラット（Brown Norway、雄、８-１２週齢、SLC社製）に、アカショウガエキス粉末を５０ｍｇにて舌下投与し、その１０分後に麻酔を施し、その１０分後に、エンドセリン－１を２．５ｐｍｏｌで硝子体内投与した。エンドセリン－１投与から１０分後と２０分後にレーザースペックルフローグラフィーにより眼血流量（ＡｖｅＡＬＬ（Ａ）：全領域の血流量、ＡｖｅＡＬＬ（Ｖ）：血管領域の血流量、ＡｖｅＡＬＬ（Ｔ）：組織領域の血流量）、脈拍、平均血圧、及び、眼圧を測定した。 (3-2. Ocular blood flow evaluation test in rats with reduced ocular blood flow)
(Test sample oral administration group)
Healthy rats (Brown Norway, male, 8-12 weeks old, manufactured by SLC) were sublingually administered red ginger extract powder at 50 mg, anesthetized 10 minutes later, and endothelin-1 administered 10 minutes later. It was administered intravitreally at 2.5 pmol. 10 and 20 minutes after endothelin-1 administration, ocular blood flow was measured by laser speckle flowgraphy (AveALL (A): blood flow in the entire region, AveALL (V): blood flow in the vascular region, AveALL (T): tissue Regional blood flow), pulse, mean blood pressure, and intraocular pressure were measured.
　（コントロール群）
　アカショウガエキス粉末を投与しない点を除き、上記内服群と同様である。すなわち、健常ラット（Brown Norway、雄、８-１２週齢、SLC社製）に麻酔を施し、その１０分後に、エンドセリン－１を２．５ｐｍｏｌで硝子体内投与した。エンドセリン－１投与から１０分後と２０分後にレーザースペックルフローグラフィーにより眼血流量（ＡｖｅＡＬＬ（Ａ）：全領域の血流量、ＡｖｅＡＬＬ（Ｖ）：血管領域血流量、ＡｖｅＡＬＬ（Ｔ）：組織領域の血流量）、脈拍、平均血圧、及び、眼圧を測定した。 (control group)
The same as the above oral administration group except that red ginger extract powder was not administered. Specifically, 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. 10 and 20 minutes after endothelin-1 administration, ocular blood flow was determined by laser speckle flowgraphy (AveALL (A): blood flow in the entire region, AveALL (V): blood flow in the vascular region, AveALL (T): tissue region blood flow rate), pulse rate, mean blood pressure, and intraocular pressure were measured.
　エンドセリン－１投与から１０分後における後眼部血流マップを図４、及び、解析後のグラフを図５～７に示す。ｓｔｕｄｅｎｔ－ｔ検定により統計処理を行った。
　また、エンドセリン－１投与から２０分後における後眼部血流マップを図８、及び、解析後のグラフを図９～１１に示す。ｓｔｕｄｅｎｔ－ｔ検定により統計処理を行った。 The posterior segment blood flow map 10 minutes after endothelin-1 administration is shown in FIG. 4, and the graphs after analysis are shown in FIGS. 5 to 7. Statistical processing was performed using the student-t test.
Further, the posterior ocular blood flow map 20 minutes after endothelin-1 administration is shown in FIG. 8, and the graphs after analysis are shown in FIGS. 9 to 11. Statistical processing was performed using the student-t test.
　図４～１１に示す通り、ショウガ（アカショウガエキス粉末）の内服群では、コントロール群と比較して、眼血流低下型モデルラットにおいても、眼血流量の増加が認められた。この眼血流量の増加作用は、血管領域の血流量（ＡｖｅＡＬＬ（Ｖ））だけでなく、組織領域の血流量（ＡｖｅＡＬＬ（Ｔ））及び全領域の血流量（ＡｖｅＡＬＬ（Ａ））において、有意に高値であることが認められた。 As shown in Figures 4 to 11, an increase in ocular blood flow was observed in the oral ginger (red ginger extract powder) group compared to the control group, even in the ocular hypoperfusion model rats. This effect of increasing the ocular blood flow is significant not only in the blood flow in the blood vessel region (AveALL (V)), but also in the blood flow in the tissue region (AveALL (T)) and the blood flow in the entire region (AveALL (A)). It was recognized that the value was high.
　結果は示していないが、エンドセリン－１投与から１０分後と２０分後における脈拍、平均血圧、及び、眼圧については、両群間で有意差は認められなかった。よって、ショウガ（アカショウガエキス）の用途によっては、他の全身状態や眼状態に影響なく、安全に摂取（投与）することができる成分であることが確認された。 Although results are not shown, no significant differences were observed between the two groups in pulse rate, mean blood pressure, and intraocular pressure 10 and 20 minutes after endothelin-1 administration. 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 the intended use.
　エンドセリン－１（ＥＴ１）の投与は、眼血流量（全領域の血流量）が低下するため（図２及び図３）、眼部の血管組織の健常性が失われている状態、眼部が老化している状態、眼循環障害が生じている状態をモデル化している。よって、ショウガを摂取（投与）することにより、眼血流の改善及び／又は維持、眼部の血管組織の健常性維持、眼部の抗老化、視野狭窄、視野欠損、若しくは暗点等の状態、各種の眼循環障害の治療及び／又は予防に効果的であることが示唆された。また、限定はされないが、エンドセリン－１（ＥＴ１）の投与は、眼血流量が低下する緑内障をモデル化している。よって、限定はされないが、ショウガを摂取（投与）することにより、眼循環障害のうち、緑内障の治療及び／又は予防に好適であることが示唆された。 Administration of endothelin-1 (ET1) reduces the ocular blood flow (blood flow in all regions) (Figures 2 and 3), leading to a state in which the health of the vascular tissue in the eye is lost and the eye It models the state of aging and the state of ocular circulation disorder. Therefore, by ingesting (administering) ginger, it can improve and/or maintain ocular blood flow, maintain the health of vascular tissue in the eye, prevent aging of the eye, and improve conditions such as visual field narrowing, visual field defects, and scotoma. It was suggested that this drug is effective in treating and/or preventing various ocular circulation disorders. Also, but not limited to, administration of endothelin-1 (ET1) models glaucoma, which reduces ocular blood flow. Therefore, it was suggested that, although not limited to, ingesting (administering) ginger is suitable for treating and/or preventing glaucoma among ocular circulation disorders.
　［試験例４：ヒトにおける寒冷負荷後の眼血流評価試験］
　生体に寒冷負荷を与えると、皮膚血管からの放熱を抑制するため、血管収縮が起こり、血流が低下する。寒冷負荷後は、時間経過と共に血流が回復する。これらの現象は、寒冷負荷に対して感受性の高いヒトでは、眼血流に対しても同様の現象が起こるとされている。試験例２及び試験例３のように、レーザースペックルフローグラフィーを用いることにより、眼血流量の変化を定量的に評価することが可能となる。寒冷負荷後の血流回復期を短縮できる物質であれば、眼血流の改善及び／又は維持に寄与し、眼部の血管組織の健常性維持、眼部の抗老化、視野狭窄、視野欠損、若しくは暗点等の状態、各種の眼循環障害の治療及び／又は予防に効果的であることが予測される。以下では、クロスオーバー比較試験により、アカショウガエキスの寒冷負荷後の眼血流に対する影響を評価した。 [Test Example 4: Ocular blood flow evaluation test after cold load in humans]
When a living body is subjected to a cold load, heat radiation from skin blood vessels is suppressed, causing vasoconstriction and a decrease in blood flow. After cold stress, blood flow recovers over time. These phenomena are said to occur with regard to ocular blood flow in humans who are highly sensitive to cold stress. As in Test Examples 2 and 3, by using laser speckle flowgraphy, it becomes possible to quantitatively evaluate changes in ocular blood flow. A substance that can shorten the blood flow recovery period after a cold load will contribute to improving and/or maintaining ocular blood flow, maintain the health of the vascular tissue in the eye, anti-aging the eye, visual field narrowing, and visual field loss. It is expected to be effective in treating and/or preventing conditions such as scotoma, scotoma, and various ocular circulation disorders. Below, the effect of red ginger extract on ocular blood flow after cold loading was evaluated using a cross-over comparative test.
　アカショウガエキス（赤ショウガエキス－Ｐ、オリザ油化株式会社製）を含有するサプリメントを被験食品とした。 A supplement containing red ginger extract (red ginger extract-P, manufactured by Oryza Yuka Co., Ltd.) was used as the test food.
　健常な被験者を、試験室に入室させ、室温２４～２５℃の試験室の椅子に座らせることで、３０分間安静待機させ試験環境に馴化させた後、被験食品を摂取させ又は非摂取の状態で、室温２４～２５℃の試験室の椅子に座り、３０分間安静待機させた。その後、試験例２及び試験例３と同様にレーザースペックルフローグラフィー（ＬＳＦＧ－ＮＡＶＩ、ソフトケア有限会社製）及び付属の解析アプリケーション（ＬＳＦＧ　ａｎａｌｙｚｅｒ）を用いて、負荷前の眼血流量を測定し寒冷負荷前の血流値（初期値）を得た。 Healthy subjects were brought into the test room and seated in a chair in the test room at a room temperature of 24 to 25°C, allowed to rest for 30 minutes and acclimatized to the test environment, and then allowed to ingest or not ingest the test food. The subjects were then seated in a chair in a test room at a room temperature of 24-25°C and allowed to rest for 30 minutes. Then, as in Test Examples 2 and 3, the ocular blood flow before loading was measured using laser speckle flowgraphy (LSFG-NAVI, manufactured by Softcare Co., Ltd.) and the attached analysis application (LSFG analyzer). Blood flow values (initial values) before cold loading were obtained.
　その後、寒冷負荷３０分前に被験食品を摂取させ又は非摂取の状態で、室温２４～２５℃の試験室の椅子に座り、３０分間安静待機させた。被験食品のアカショウガ抽出物自体（賦形剤を含まない）の含有量は、乾燥固形分含量として、約１０ｍｇ／日である。 Thereafter, the subjects were allowed to ingest the test food 30 minutes before the cold load or were not ingested, and were allowed to sit on a chair in a test room at a room temperature of 24 to 25°C and rest for 30 minutes. The content of the red ginger extract itself (without excipients) in the test food was approximately 10 mg/day as a dry solid content.
　初期値の測定終了後、右手にニトリル手袋を装着し、４０℃の温水に右手首まで２分間浸漬させた。その後、４℃の冷水に右手首まで１分間浸漬させ寒冷負荷を行った。寒冷負荷後、速やかにペーパータオル等で水分を拭き取り、眼底血流の測定を寒冷負荷４分後および６分後に実施した。十分なウォッシュアウト期間を設け、同一被験者らに対して、クロスオーバー条件下にて、同様の試験を実施した。 After completing the measurement of the initial values, a nitrile glove was put on the right hand, and the right wrist was immersed in warm water at 40°C for 2 minutes. Thereafter, the right wrist was immersed in cold water at 4° C. for 1 minute to perform a cold load. After the cold load, moisture was immediately wiped off with a paper towel or the like, and fundus blood flow was measured 4 and 6 minutes after the cold load. A similar test was conducted on the same subjects under crossover conditions with a sufficient washout period.
　本試験例における眼底血流測定は、視神経乳頭部の組織領域の血流量（ＭＢＲ平均値）を測定している。また、対象食品を摂取した後、寒冷負荷４分後の眼底血流の測定において、視神経乳頭部の温度が下がった被験者を、レスポンダー（本試験において９名）として評価した。結果を図１２に示す。上側の折れ線グラフが被験食品群であり、下側の折れ線グラフが非摂取群である。図１２において、縦軸は、ＭＢＲの変化量の平均値を示す。 The fundus blood flow measurement in this test example measures the blood flow rate (MBR average value) in the tissue region of the optic nerve head. In addition, in the measurement of fundus blood flow 4 minutes after cold exposure after ingesting the target food, subjects whose optic disc temperature decreased were evaluated as responders (nine subjects in this study). The results are shown in FIG. The upper line graph is the test food group, and the lower line graph is the non-ingestion group. In FIG. 12, the vertical axis indicates the average value of the amount of change in MBR.
　図１２に示す通り、ショウガ（アカショウガエキス）の摂取群では、コントロール群と比較して、寒冷負荷後に眼血流量を増加させ、血流回復期を短縮できることが認められた。よって、ショウガ（アカショウガエキス）は、眼血流の改善及び／又は維持に寄与し、眼部の血管組織の健常性維持、眼部の抗老化、視野狭窄、視野欠損、若しくは暗点等の状態、各種の眼循環障害の治療及び／又は予防に効果的であることが予測される。 As shown in FIG. 12, in the ginger (red ginger extract) intake group, it was observed that the ocular blood flow could be increased and the blood flow recovery period could be shortened after a cold load, compared to the control group. Therefore, ginger (red ginger extract) contributes to improving and/or maintaining ocular blood flow, maintains the health of the vascular tissue in the eye, anti-aging the eye, and prevents visual field narrowing, visual field defects, scotoma, etc. It is expected to be effective in the treatment and/or prevention of various ocular circulation disorders.
　上記実施例において用いたアカショウガエキス（赤ショウガエキス－Ｐ、オリザ油化株式会社製）は、根茎から含水エタノールで抽出され、［６］－ｇｉｎｇｅｒｏｌおよび［６］－ｓｈｏｇａｏｌの総含有量が６．０質量％以上であり、タンニンを１．５質量％以上含み、賦形剤としてシクロデキストリンが等量で混合されている製剤である。
  The red ginger extract (red ginger extract-P, manufactured by Oryza Yuka Co., Ltd.) used in the above examples was extracted from the rhizome with aqueous ethanol, and the total content of [6]-gingerol and [6]-shogaol was 6. .0% by mass or more, tannins in an amount of 1.5% by mass or more, and an equal amount of cyclodextrin mixed as an excipient.

Claims (10)

  1. 　ショウガ及び／又はその抽出物を含有する、眼血流の改善及び／又は維持用組成物。 A composition for improving and/or maintaining ocular blood flow containing ginger and/or its extract.
  2. 　ショウガ及び／又はその抽出物を含有する、眼部の血管組織の健常性維持用組成物。 A composition for maintaining the health of vascular tissue in the eye, containing ginger and/or an extract thereof.
  3. 　ショウガ及び／又はその抽出物を含有する、眼部の抗老化用組成物。 An anti-aging composition for the eye area containing ginger and/or its extract.
  4. 　ショウガ及び／又はその抽出物を含有する、眼部の健常性、視野狭窄、視野欠損、若しくは暗点の出現又は拡大の改善及び／又は維持用の組成物。 A composition for improving and/or maintaining ocular health, visual field narrowing, visual field defects, or the appearance or expansion of scotoma, containing ginger and/or its extract.
  5. 　ショウガ及び／又はその抽出物を含有する、眼循環障害の治療及び／又は予防用の組成物。 A composition for the treatment and/or prevention of ocular circulation disorders containing ginger and/or its extract.
  6. 　眼循環障害が、緑内障、網膜静脈閉塞症、網膜動脈閉塞症、眼虚血症候群、内頚動脈閉塞症、腎性網膜症、一過性黒内障、加齢黄斑変性である請求項５に記載の組成物。 The composition according to claim 5, wherein the ocular circulation disorder is glaucoma, retinal vein occlusion, retinal artery occlusion, ocular ischemia syndrome, internal carotid artery occlusion, renal retinopathy, transient amaurosis, or age-related macular degeneration. thing.
  7. 　医薬品又は飲食品である、請求項１に記載の組成物。 The composition according to claim 1, which is a pharmaceutical product or a food or drink product.
  8. 　口腔内崩壊錠、チュアブル錠、飴剤、顆粒剤、散剤又は液剤である請求項７に記載の組成物。 The composition according to claim 7, which is an orally disintegrating tablet, a chewable tablet, a candy, a granule, a powder, or a liquid.
  9. 　ショウガ及び／又はその抽出物が、アカショウガ及び／又はその抽出物である、請求項１に記載の組成物。 The composition according to claim 1, wherein the ginger and/or its extract is red ginger and/or its extract.
  10. 　眼血流が、網膜及び／又は脈絡膜の血流である、請求項１に記載の組成物。
          The composition according to claim 1, wherein the ocular blood flow is retinal and/or choroidal blood flow.
PCT/JP2023/026874 2022-07-22 2023-07-21 Composition for improving ocular blood flow WO2024019171A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2022-117229 2022-07-22
JP2022117229 2022-07-22

Publications (1)

Publication Number Publication Date
WO2024019171A1 true WO2024019171A1 (en) 2024-01-25

Family

ID=89617947

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2023/026874 WO2024019171A1 (en) 2022-07-22 2023-07-21 Composition for improving ocular blood flow

Country Status (2)

Country Link
TW (1) TW202408561A (en)
WO (1) WO2024019171A1 (en)

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH06183959A (en) * 1992-12-17 1994-07-05 Pola Chem Ind Inc Blood circulation promoter
JP2007051090A (en) * 2005-08-18 2007-03-01 Pharma Foods International Co Ltd Blood flow improving agent containing egg white peptide as active ingredient
JP2010100561A (en) * 2008-10-23 2010-05-06 Mitsukan Group Honsha:Kk Ciliary muscle relaxant
JP2018188438A (en) * 2017-05-10 2018-11-29 ロート製薬株式会社 Composition for prevention, improvement or treatment of posterior eye diseases
JP2019055917A (en) * 2017-09-20 2019-04-11 御木本製薬株式会社 Endothelin-1 inhibitor

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH06183959A (en) * 1992-12-17 1994-07-05 Pola Chem Ind Inc Blood circulation promoter
JP2007051090A (en) * 2005-08-18 2007-03-01 Pharma Foods International Co Ltd Blood flow improving agent containing egg white peptide as active ingredient
JP2010100561A (en) * 2008-10-23 2010-05-06 Mitsukan Group Honsha:Kk Ciliary muscle relaxant
JP2018188438A (en) * 2017-05-10 2018-11-29 ロート製薬株式会社 Composition for prevention, improvement or treatment of posterior eye diseases
JP2019055917A (en) * 2017-09-20 2019-04-11 御木本製薬株式会社 Endothelin-1 inhibitor

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
TSUDA, TAKANORI; OSAWA, TOSHIHIKO : "Anthocyanin", JOURNAL OF THE EYE, MEDICAL AOI PUBLICATION, JP, vol. 25, no. 10, 1 January 2008 (2008-01-01), JP , pages 1393 - 1395, XP009552733, ISSN: 0910-1810 *

Also Published As

Publication number Publication date
TW202408561A (en) 2024-03-01

Similar Documents

Publication Publication Date Title
JP6936932B2 (en) Flavonoid composition and usage
US20070036873A1 (en) Method of treatment or management of stress
US7932288B2 (en) Composition for relieving subjective symptoms of fatigue
US20180104299A1 (en) Use of saffron and/or safranal and/or crocin and/or picrocrocin and/or derivatives thereof as a satiation agent for the treatment of obesity
CN101903033A (en) The purposes of the extract of making by Folium Ginkgo
JP2008528483A (en) Mixed herbal medicine extract of 337 root, ripening yellow, and quince skin, and composition for preventing and treating arthritis comprising the same as an active ingredient
JP2011522844A (en) Composition for reducing blood glucose level and use thereof
JP4873904B2 (en) Ocular blood flow disorder improving agent
KR101987418B1 (en) A composition comprising herbal mixture extract for neuroprotection
WO2020179747A1 (en) Hif inhibitory composition
KR102348044B1 (en) Composition for preventing, improving or treating burn out syndrome
WO2024019171A1 (en) Composition for improving ocular blood flow
KR102009966B1 (en) Composition comprising the extract of platycarya strobilacea as and effective component for treatment, improvement or prevention of stroke
TWI437998B (en) Use of an extract of ilex latifoliain
KR101660834B1 (en) Anti-diabetic effects of Gypenoside 75
JP7435442B2 (en) Composition for improving vascular endothelial function or peripheral blood flow
KR102245027B1 (en) Composition for improving sleep disorder containing lettuce and Scutellariae extract as an active ingredient
WO2019168185A1 (en) Food composition for preventing and/or reducing risk of abnormalities in posterior segment of eye
JP4669077B1 (en) Autonomic nerve regulator containing asparagus pseudo-leaf as active ingredient
KR20040092232A (en) Composition of Korean Red Ginseng for Improving Sexual Function, Manufacturing Method the Same and Its Use
JP3345650B2 (en) Hypertension inhibitor
JP2020015679A (en) Compositions for improving lower urinary tract symptoms
WO2021117547A1 (en) Food for preventing or ameliorating lower urinary tract symptoms
KR20220076720A (en) Food composition for preventing or improving Mibyeong
JP2024017059A (en) Common cold symptom inhibitor

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 23843094

Country of ref document: EP

Kind code of ref document: A1