WO2007141898A1 - Agent améliorant la tension oculaire - Google Patents

Agent améliorant la tension oculaire Download PDF

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Publication number
WO2007141898A1
WO2007141898A1 PCT/JP2006/326290 JP2006326290W WO2007141898A1 WO 2007141898 A1 WO2007141898 A1 WO 2007141898A1 JP 2006326290 W JP2006326290 W JP 2006326290W WO 2007141898 A1 WO2007141898 A1 WO 2007141898A1
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WO
WIPO (PCT)
Prior art keywords
crocetin
eye strain
food
eye
acid
Prior art date
Application number
PCT/JP2006/326290
Other languages
English (en)
Japanese (ja)
Inventor
Takashi Kahara
Naofumi Umigai
Katsura Funayama
Mariko Abe
Masahiro Takahashi
Original Assignee
Riken Vitamin Co., Ltd.
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
Priority claimed from JP2006154520A external-priority patent/JP2007031426A/ja
Application filed by Riken Vitamin Co., Ltd. filed Critical Riken Vitamin Co., Ltd.
Publication of WO2007141898A1 publication Critical patent/WO2007141898A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
    • A61K31/202—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids having three or more double bonds, e.g. linolenic
    • 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
    • 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
    • A61P27/10—Ophthalmic agents for accommodation disorders, e.g. myopia

Definitions

  • the present invention relates to an eye strain improving agent, food and drink, and a method for preventing or improving eye strain, comprising crocetin or a pharmacologically acceptable salt thereof as an active ingredient.
  • Eye strain refers to a state in which various subjective symptoms such as eye fatigue, eyes hurt, things are difficult to see, dizziness, and head ache are not resolved by rest.
  • causes of eye strain include power of eye overuse and mental tension caused by reading, gazing work, observation work, etc.
  • eye strain caused by VDT (Visual Display Terminal) work has been extremely high. Yes.
  • Force Eye strain is mostly regulated eye strain caused by abnormal regulation. It has been pointed out that accommodative eye strain occurs because ciliary muscles are in an excessively tensioned state due to long-term gaze work and the like, resulting in a decrease in the eye regulation function.
  • crocetin increases the blood flow in the retina of the rabbit and helps to restore the function of the retina (see Non-Patent Document 1) and the inflammation of the eye of the rabbit that is induced by PGE2. It has been reported to suppress the concentration dependently (see Non-Patent Document 2). However, the effect of crocetin on improving eye strain was unclear!
  • Patent Document 1 Japanese Patent Laid-Open No. 2001-178408, Claim 3 Patent Document 2: JP-A-11 246455, Claims 7 and 9
  • Patent Document 3 International Publication No.01Z001798 Specification
  • Patent Document 4 Specification of International Publication No.02Z094253
  • Non-patent literature l Xuan B, 4 others, “Effects of crocin analogs on ocular bio od flow and retinal functionj, Journal of Ocular Phamacology and Therapeutics, 1999, vol. 15, p. 143—152
  • Non-Patent Document 2 Nagaki Y, 5 others, ⁇ Effects of oral administration of Gard eniae Fructus extract and intravenous injection of Crocetin on lip ⁇ polysaccharide and prostaglandin E2— induced elevation of aqueou s flare in pigmented rabbitsj, The American Journal of Chinese M edicine, 2003, vol. 31, p. 729— 738
  • the present invention relates to an eye fatigue improving agent containing a compound having an eye fatigue improving effect as an active ingredient, a food or drink used for the prevention or recovery of eye fatigue, and the prevention or The purpose is to provide an improvement method.
  • crocetin which is a kind of carotenoid pigment, has an effect of improving eye strain, and based on this finding.
  • the present invention was completed in a short time.
  • the present invention provides:
  • Crocetin or a pharmacologically acceptable salt thereof is administered to a person who may cause eye strain or a person who has eye strain, or How to improve, It is made from.
  • the eye strain improving agent and food and drink of the present invention have various symptoms of eye strain (for example, 1) eyes are tired, 2) eyes are painful, 3) eyes are hazy, 4) shoulders are stiff 5) Excellent effect in reducing head pain etc.
  • eye strain improving agent or food or drink of the present invention By taking the eye strain improving agent or food or drink of the present invention before, during or after work causing eye strain, eye strain can be prevented or recovered. .
  • Crocetin used in the present invention is Crocetin used in the present invention.
  • This crocetin is usually obtained by hydrolyzing crocin (a digentiobiose ester of crocetin), which is a carotenoid yellow pigment. Crocin is the power of gardenia augusta MERRIL var. It is used well.
  • the method for extracting the above-mentioned plant basic force crocin for example, dried fruit strength of ground gardenia water or alcohol (eg, methanol, ethanol, etc.), or A known method such as extraction using a mixed solution thereof is used.
  • the extraction condition at this time is about 30 to 40 ° C, which is about 1 to 18 hours at room temperature (about 0 to 30 ° C) to 50 ° C. ⁇ 4 hours is more preferred.
  • the extraction operation is usually repeated several times.
  • Crocin obtained Next, a solution obtained by dissolving an extract containing lysate, a concentrated solution of the extract or a concentrated dried product in an appropriate solvent (for example, water or ethanol) is then subjected to a hydrolysis step.
  • Hydrolysis of crocin may be carried out according to a conventional method, and is usually carried out in the presence of acid, alkali or a suitable hydrolase.
  • the acid include hydrochloric acid, sulfuric acid, and phosphoric acid
  • examples of the alkali include sodium hydroxide, potassium hydroxide, sodium carbonate, and potassium carbonate.
  • hydrolases include ⁇ -darcosidase.
  • the acid, alkali or enzyme is preferably added to a solution containing crocin after being dissolved or dispersed in a suitable solvent (eg, water or ethanol).
  • crocin is preferably hydrolyzed in the presence of an alkali.
  • the hydrolysis conditions are not particularly limited, but with stirring, preferably at about 20 to 70 ° C for about 1 to 24 hours, particularly preferably at about 40 to 60 ° C for about 3 to 5 hours. It is.
  • the hydrolysis of crocin is hydrolysis with an alkali
  • an appropriate amount of an aqueous solution of an inorganic acid such as hydrochloric acid, sulfuric acid or phosphoric acid, or an organic acid such as cuenic acid is added to the reaction solution.
  • the solution is adjusted to pH 4 or less, preferably about pH 1 to 3, or the reaction solution is added to an aqueous solution of an inorganic acid such as hydrochloric acid, sulfuric acid or phosphoric acid, or an organic acid such as citrate.
  • the crocetin can be precipitated by adjusting the pH to about 4 or less, preferably about pH 1 to 3. Thereafter, the crocetin can be recovered as a pasty solid by centrifuging the mixture or filtering through a filter paper or filter cloth.
  • crocetin When crocin is hydrolyzed with acid, the produced crocetin precipitates in a free form insoluble in water, and thus the reaction solution is obtained as a suspension. After completion of the reaction, crocetin can be recovered as a pasty solid by centrifuging the obtained suspension or filtering through a filter paper or filter cloth.
  • Crocetin (paste-like solid) obtained as described above usually has acid, neutralized salt, and impurities derived from raw materials attached to the surface of the solid, so that the impurities are removed.
  • a cleaning process is performed for the purpose.
  • the treatment may be performed using a known method, for example, washing the pasty solid with a sufficient amount of water.
  • shelf type The solid material washed with water, for example, is dried at a temperature not exceeding about 50 ° C. in an atmosphere of nitrogen gas, for example, by using an air dryer or a vacuum dryer, and the water remaining on the solid material is removed. preferable.
  • the crocetin thus obtained is produced by hydrolysis of substances other than crocetin, such as lipids and their degradation products, polyphenols such as chlorogenic acid, and washing. It is preferable to further purify the crocetin since it may contain saccharides such as glucose and gentiobiose that are not completely removed.
  • the method for purifying the crocetin is not limited, and known methods such as column chromatography and recrystallization are used.
  • the crocetin used in the present invention is crocetin having a purity of about 70% by mass or more, preferably crocetin having a purity of about 90% by mass or more, more preferably having a purity of about 95% by mass or more. Most preferably.
  • the purity of crocetin is calculated based on the color value of pure crocetin.
  • the color value is a value measured by the [color value measuring method] described in Examples below.
  • pharmacologically acceptable salts of crocetin include, for example, alkali metal salts such as sodium and potassium, alkaline earth metal salts such as magnesium and calcium, pyridine, dimethylamine, jetylamine, ethanol And pharmaceutically acceptable salts of organic amino compounds such as min.
  • crocetin which is effective in the present invention, has an effect of improving eye strain, it is used as an eye fatigue improving agent containing the crocetin or a pharmacologically acceptable salt thereof as an active ingredient, or for preventing eye fatigue. Or it is useful as a food or drink for the purpose of recovery.
  • the eye fatigue-improving agent of the present invention and the food and drink used for preventing or recovering eye fatigue are used as such or pharmaceutically acceptable for the crocetin or a pharmacologically acceptable salt thereof.
  • a crocetin-containing composition such as an oil or fat composition mainly composed of crocetin or a pharmacologically acceptable salt thereof, an oZw type emulsion, a wZo type emulsion or a soluble salt solution.
  • the food or drink of the present invention may be produced by producing a product according to a conventional method and adding this crocetin-containing composition to food or drink.
  • the food and drink can take any food form such as a solid food, a cream-like or jam-like semi-solid food, a gel food, and a beverage.
  • food and drink include soft drinks, drops, candy, chewing gum, chocolate, gummi, yogurt, ice cream, pudding, jelly confectionery, cookies, margarine, shortening, mayonnaise and dressing.
  • the foods and beverages mentioned above prevent specific health foods with the indication that they are used for the prevention or recovery of eye strain, or the accumulation of eye strain and various symptoms associated therewith. It is also useful as a health food intended to recover.
  • Additives, food materials, food ingredients and food additives used in the preparation of the above-mentioned preparations and foods and drinks include, for example, excipients (lactose, dextrin, corn starch, crystal cell mouth etc.), lubricants, etc.
  • Agents magnesium stearate, sucrose fatty acid ester, glycerin fatty acid ester, etc.
  • disintegrating agents carboxymethylcellulose calcium, anhydrous calcium phosphate, calcium carbonate, etc.
  • binders starch glue, hydroxypropyl cellulose) , Gum arabic liquid, etc.
  • solubilizers gum arabic, polysorbate 80, etc.
  • sweeteners sucgar, fructose, glucose liquid sugar, honey, aspartame, etc.
  • coloring agents () Riboflavin), preservatives (such as sorbic acid, methyl parabenzoate, sodium sulfite) ), Thickeners (sodium alginate, sodium carboxymethylcellulose, sodium polyacrylate, etc.), anti-oxidants (dibutylhydroxytoluene (BHT), butylhydroxy-sol (BHA), ascorbic acid, Tocopherols, etc.), flavors (such as heart force, strawberry flavors), sour seasonings
  • crocetin or a pharmacologically acceptable salt thereof varies depending on the symptoms of eye strain, its purpose, use, etc., but is not uniform.
  • crocetin purity 100 mass 0/0, usually about 0.0001 to 50 weight 0/0, good Mashiku about 0.001 to 20 wt%, more preferably about 0.01 to 10 % By mass.
  • the content of crocetin or a pharmacologically acceptable salt thereof is usually about 0 in terms of crocetin having a purity of 100% by mass with respect to the total mass of the food or drink. . 00003-10 weight 0/0, preferably from about 0.01 to 5 weight 0/0, more preferably from about 1 to 5 mass%.
  • the adult dose of crocetin or a pharmacologically acceptable salt thereof (about 60 kg)
  • the daily dose should be converted to crocetin with a purity of 100% by mass. In general, it is in the range of about 0.1 to 500 mg, preferably about 1 to 200 mg, more preferably about 2 to 50 mg. This dose may be taken in one or several divided doses. However, the actual dose should be determined in consideration of the purpose and intake situation (degree of eye strain, gender, age, health status, etc.).
  • crocetin or its pharmacologically acceptable Desirable salt should be set to a dosage of about 0.1 Olg to: LOOmg, preferably about 0.1 to 50 mg, more preferably about 0.1 to 15 mg.
  • the eye strain improving agent of the present invention can be used in combination with other drugs or supplements for the purpose of recovery from eye strain.
  • drugs and supplements include vitamins (for example, vitamin A, vitamin B, vitamin B, vitamin B, vitamin B, vitamin C, vitamin B).
  • Tamine E nicotinamide, pantothenic acid, etc.
  • amino acids eg, taurine, aspartic acid or its salts
  • anthocyanins eg, strawberry concentrate, cranberry juice, black chokeberry juice, blueberry juice
  • Plum concentrated juice etc.
  • the method for preventing or ameliorating eye strain causes crocetin or a pharmacologically acceptable salt thereof to occur in a person, particularly a person who may cause eye strain or eye strain. It is a method to administer to a person. Examples of the person who may cause eye strain include a person who looks at a display such as a computer or a TV for a long time in daily life.
  • crocetin or a pharmacologically acceptable salt thereof are as described above.
  • Methanol-water mixture (1: 1) (V / V) (600 mL) was added to 300 g of dried dried fruit of gardenia and stirred at room temperature for 3 hours, followed by suction filtration. After filtration, add 600 mL of methanol / water mixture (1: 1) (VZV) to the extraction residue, stir at room temperature for 30 minutes, and repeat suction filtration twice to obtain a total of about 1800 mL of extract as filtrate. Obtained.
  • Crocetin purity (%) X I 0 0
  • the color value ( ⁇ ) is “Food Additives other than Chemical Synthetic Products Voluntary Standard (Second Edition)”, day lcm
  • liquid layer length lcm is at the maximum absorption part around 420 nm.
  • Lactose 1 Lactose 1 ) 2 3 1 .6 2 4 0 .0
  • subject's subjective symptoms associated with eye strain were as follows: 1) eyes are tired, 2) eyes are painful, 3) eyes are hazy, 4) For the five items of stiff shoulders and 5) head pain, use the visual analog scale method to fill in a line on a 10cm line segment from 0 (not felt) to 10 (extremely felt). It was.
  • Group A was the test drug administration group and group B was the control drug administration group.
  • group B was the control drug administration group.
  • HFC appearance frequency
  • Test drug administration group (before ingestion) vs Test drug administration group (after ingestion): Risk factor 5%
  • Test drug administration group (after ingestion) vs. control drug administration group (after ingestion): Risk 1%

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
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  • Pharmacology & Pharmacy (AREA)
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  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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Abstract

La présente invention concerne un agent améliorant la tension oculaire, qui contient en tant que principe actif un composé ayant la capacité d'améliorer ladite tension oculaire, ainsi qu'un aliment, ou un breuvage, destiné à être utilisé pour prévenir l'apparition d'une tension oculaire ou en permettre la disparition. L'agent améliorant et l'aliment, ou le breuvage, permettant d'améliorer la tension oculaire sont caractérisés par le fait qu'ils contiennent de la crocétine en tant que principe actif, ce composé étant représenté par la formule, [formule chimique 1] ou un sel pharmacologiquement acceptable du composé.
PCT/JP2006/326290 2006-06-02 2006-12-28 Agent améliorant la tension oculaire WO2007141898A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2006154520A JP2007031426A (ja) 2005-06-20 2006-06-02 眼精疲労改善剤
JP2006-154520 2006-06-02

Publications (1)

Publication Number Publication Date
WO2007141898A1 true WO2007141898A1 (fr) 2007-12-13

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114939142A (zh) * 2022-05-10 2022-08-26 仙乐健康科技股份有限公司 一种用于抗蓝光的组合物

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999018970A1 (fr) * 1997-10-14 1999-04-22 Senju Pharmaceutical Co., Ltd. Medicaments a action preventive et remedes contre les troubles circulatoires ophtalmiques
WO2001085183A2 (fr) * 2000-05-08 2001-11-15 N.V. Nutricia Preparation pour la prevention et le traitement de troubles oculaires
WO2002094253A1 (fr) * 2001-05-24 2002-11-28 Fuji Chemical Industry Co., Ltd. Agents attenuant une erreur de fonction de controle de l'oeil
JP2005225842A (ja) * 2004-02-16 2005-08-25 Riken Vitamin Co Ltd 脳機能改善剤
WO2006112283A1 (fr) * 2005-04-13 2006-10-26 Riken Vitamin Co., Ltd. Agent anti-fatigue

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999018970A1 (fr) * 1997-10-14 1999-04-22 Senju Pharmaceutical Co., Ltd. Medicaments a action preventive et remedes contre les troubles circulatoires ophtalmiques
WO2001085183A2 (fr) * 2000-05-08 2001-11-15 N.V. Nutricia Preparation pour la prevention et le traitement de troubles oculaires
WO2002094253A1 (fr) * 2001-05-24 2002-11-28 Fuji Chemical Industry Co., Ltd. Agents attenuant une erreur de fonction de controle de l'oeil
JP2005225842A (ja) * 2004-02-16 2005-08-25 Riken Vitamin Co Ltd 脳機能改善剤
WO2006112283A1 (fr) * 2005-04-13 2006-10-26 Riken Vitamin Co., Ltd. Agent anti-fatigue

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
BO XUAN ET AL.: "Effects of crocin analogs on ocular blood flow and retinal function", JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS, vol. 15, no. 2, 1999, pages 143 - 152, XP008043342 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114939142A (zh) * 2022-05-10 2022-08-26 仙乐健康科技股份有限公司 一种用于抗蓝光的组合物
CN114939142B (zh) * 2022-05-10 2023-12-26 仙乐健康科技股份有限公司 一种用于抗蓝光的组合物

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