WO2024019171A1 - Composition destinée à améliorer le débit sanguin oculaire - Google Patents

Composition destinée à améliorer le débit sanguin oculaire Download PDF

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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
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Prior art keywords
ginger
blood flow
extract
ocular
composition
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PCT/JP2023/026874
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English (en)
Japanese (ja)
Inventor
徹 中澤
孝太 佐藤
美和子 蔀
寿枝 上田
恒星 塚本
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ロート製薬株式会社
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Publication of WO2024019171A1 publication Critical patent/WO2024019171A1/fr

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    • 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.

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Abstract

Le but de la présente invention est de fournir une composition qui atténue les affections liées au débit sanguin oculaire, par évaluation des effets sur le débit sanguin oculaire. L'invention concerne une composition destinée à améliorer et/ou maintenir le débit sanguin oculaire, ladite composition contenant du Zingiber officinale et/ou un extrait de celui-ci. L'invention concerne également une composition destinée à préserver la santé des tissus vasculaires dans la région oculaire, une composition anti-vieillissement de la région oculaire, une composition destinée à améliorer et/ou préserver la santé de la région oculaire, à atténuer le rétrécissement du champ visuel, les défauts du champ visuel ou l'apparition ou l'extension d'une tache sombre, ainsi qu'une composition destinée à traiter et/ou prévenir des troubles de la circulation oculaire, chaque composition contenant l'ingrédient susmentionné.
PCT/JP2023/026874 2022-07-22 2023-07-21 Composition destinée à améliorer le débit sanguin oculaire WO2024019171A1 (fr)

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH06183959A (ja) * 1992-12-17 1994-07-05 Pola Chem Ind Inc 血行促進剤
JP2007051090A (ja) * 2005-08-18 2007-03-01 Pharma Foods International Co Ltd 卵白ペプチドを有効成分として含有する血流改善剤
JP2010100561A (ja) * 2008-10-23 2010-05-06 Mitsukan Group Honsha:Kk 毛様体筋緊張緩和剤
JP2018188438A (ja) * 2017-05-10 2018-11-29 ロート製薬株式会社 後眼部疾患の予防、改善、又は治療用組成物
JP2019055917A (ja) * 2017-09-20 2019-04-11 御木本製薬株式会社 エンドセリン−１抑制剤

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH06183959A (ja) * 1992-12-17 1994-07-05 Pola Chem Ind Inc 血行促進剤
JP2007051090A (ja) * 2005-08-18 2007-03-01 Pharma Foods International Co Ltd 卵白ペプチドを有効成分として含有する血流改善剤
JP2010100561A (ja) * 2008-10-23 2010-05-06 Mitsukan Group Honsha:Kk 毛様体筋緊張緩和剤
JP2018188438A (ja) * 2017-05-10 2018-11-29 ロート製薬株式会社 後眼部疾患の予防、改善、又は治療用組成物
JP2019055917A (ja) * 2017-09-20 2019-04-11 御木本製薬株式会社 エンドセリン−１抑制剤

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 *

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