• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
  • 引用文献
  • 法律状态
  • 优先权
    • 专利摘要:
    A vision performance enhancing composition and method to enhance vision performance using alanylglutamine or a salt of alanylglutamine as an active ingredient.
    公开号:AU2013226772A1
    申请号:U2013226772
    申请日:2013-02-28
    公开日:2014-09-25
    发明作者:Takeshi Ikeda；Koji Morishita；Ryusuke Nakagiri；Mami Nebashi
    申请人:Kyowa Hakko Bio Co Ltd；
    IPC主号:A61K38-00
    专利说明:
    WO 2013/129700 PCT/JP2013/056204 DESCRIPTION METHODS AND COMPOSITIONS FOR ENHANCEMENT OF VISION PERFORMANCE TECHNICAL FIELD OF THE INVENTION 5 [0001] The present invention relates to compositions containing alanylglutamine or a salt thereof as an active ingredient for the enhancement of vision performance. 20 BACKGROUND OF THE INVENTION [0002] The ability to see objects and respond to visual stimuli declines during periods of moderate to severe physical exertion. In particular, the ability to see and respond to stimuli 15 presented in the periphery of the visual field declines compared to the ability to respond to visual stimuli presented in the central portion of the visual field (Ando et al., Int J Sports Med, Dec 2008; 29(12): 994-8. Epub 2008 Jul 3.). [0003] 20 Alanylglutamine is a dipeptide containing two amino acids, alanine and glutamine, and is immediately degraded into alanine and glutamine in the body (refer to "Clinical Science", 1988, Vol. 75, No. 5, p. 463-8). The action of glutamine is known to have many effects on physiological functions, such as the 25 regulation of skeletal muscle protein metabolism, repair of small intestine mucosa, and improvement of immunofunction, and it has been reported that the effects of'alanine on physiological functions include an action to suppress blood sugar levels in diabetes patients (refer to "L-Alanyl-L 30 Glutamine", Kyowa Hakko Co., Ltd., 2006, p. 1). [0004] Alanylglutamine is superior in heat stability and solubility in aqueous solutions compared to glutamine, which has low-solubility and poor stability (refer to "L-Alanyl-L 35 Glutamine", Kyowa Hakko Co., Ltd., 2006, p. 3), and is used in 1 WO 2013/129700 PCT/JP2013/056204 parenteral nutritional agents as a glutamine supply source. [0005] Nonetheless, alanylglutamine is not known to have an action to enhance vision performance. 5 SUMMARY OF THE INVENTION [0006) There is a demand for pharmaceutical products and nutritional foods, etc., that improve symptoms and create lo fulfilling lives for people having subjective symptoms of decreased vision performance attributed to exercise, including decreased peripheral vision and decreased visual reaction time. Specifically, an object of the present invention is to offer a composition which enhances vision performance. 15 [0007] One aspect of the present invention is a vision performance enhancing composition containing alanylglutamine or a salt thereof as an active ingredient. [0008] 20 Another aspect of the present invention is a method of enhancing vision performance by administering an effective amount of alanylglutamine or a salt thereof to a subject in need. [0009] Yet another aspect of the present invention is a use of 25 alanylglutamine or a salt thereof for producing a vision performance enhancing composition. BRIEF DESCRIPTION OF THE DRAWINGS [0010] 30 Figure 1 shows a subject participating in a trial. [0011] Figure 2 is a graph depicting visual reaction time in subjects after administration of a vision performance enhancing composition of the invention. 35 [0012] 2 WO 2013/129700 PCT/JP2013/056204 Figure 3 is a graph depicting motor response time in subjects after administration of a vision performance enhancing composition of the invention. 5 DETAILED DESCRIPTION OF THE INVENTION [0013] In the composition of the present invention, alanine and glutamine are the amino acids that constitute alanylglutamine. Each may be L- or D-forms respectively, and the L-forms are 10 preferred. [0014] Salts of alanylglutamine include acid addition salts, metal salts, ammonium salts, organic amine addition salts, amino acid addition salts, and the like. 15 [0015] The acid addition salts include inorganic acid salts such as hydrochloride, hydrosulfate, nitrate and phosphate; and organic acid salts such as acetate, maleate, fumarate, citrate, malate, lactate, a-ketoglutarate, gluconate and caprylate. 20 [0016] The metal salts include alkali metal salts such as sodium salt and potassium salt; alkaline earth metal salts such as calcium salt; magnesium salt; aluminum salt; zinc salt, and the like. 25 [0017] Ammonium salts include salts of ammonium, tetramethylammonium, and the like. [0018] Organic amine addition salts include salts of morpholine, 30 piperidine, and the like. [0019] Amino acid addition salts include salts of glycine, phenylalanine, lysine, aspartic acid, glutamic acid, and the like. 35 [0020] 3 WO 2013/129700 PCT/JP2013/056204 Alanylglutamine may be produced according to any method such as synthetic method, enzymatic method, or fermentation method. [0021] 5 Methods for producing alanylglutamine include, for example, those cited in Bulletin of the Chemical Society of Japan, 34, 739 (1961), 35, 1966 (1962), 37, 200 (1964), European Patent No. 311057, German Patent No. 3206784, Japanese Unexamined Patent Publication No. H6-234715, and W02004/058960. 10 [0022] Commercial products (those manufactured by Kyowa Hakko, Co., Ltd., Kokusan Kagaku, Co., Ltd., and Bachem AG, etc.) may be used for alanylglutamine. [0023] 15 Vision performance can be improved by administering the compositions of the present invention to persons having decreased vision performance. [0024] In the present invention, sports vision means the ability 20 to see objects during sport activities, and includes peripheral vision during exercise and visual reaction time during exercise. [0025] Alanylglutamine or a salt thereof may be administered as it is as the vision performance enhancing agent of the present 25 invention, but preferably alanylglutamine is provided in any of a variety of pharmaceutical preparations. [0026] These pharmaceutical preparations contain alanylglutamine or a salt thereof as an active ingredient, but may also contain 3o any other therapeutic active ingredients. Further, these pharmaceutical preparations may be produced by any method well known in the technical field of pharmaceutics by mixing active ingredients with one or more pharmaceutically acceptable carriers. 35 [0027] 4 WO 2013/129700 PCT/JP2013/056204 It is desirable to use the pharmaceutical preparation through a dosing route that is the most effective for the therapy, and examples thereof include oral administration and parenteral administration such as intravenous administration, 5 intraperitoneal administration, or subcutaneous administration; but oral administration is preferred. [00281 The dosage form may be oral preparations, such as tablets, powders, granules, pills, suspensions, emulsions, 20 infusions/decoctions, capsules, syrups, liquid preparations, elixirs, extracts, tinctures and fluid extracts, or parenteral preparations, such as injections, IV drip, creams and suppositories; but oral preparations are preferable. [0029] 15 When preparing oral preparations, excipients may be used such as fillers, binders, disintegrators, lubricants, dispersing agents, suspension agents, emulsifiers, diluents, buffers, antioxidant agents, microbial inhibitors, and the like. [0030] 20 Liquid preparations suitable to oral administration, for example, syrups, can be formulated by adding: water; a saccharide such as sucrose, sorbitol, or fructose; a glycol such as polyethylene glycol, or propylene glycol; an oil such as sesame oil, olive oil, or soybean oil; an antiseptic such as a 25 p-hydroxybenzoate ester; a preservative such as a paraoxybenzoate derivative like methyl paraoxybenzoate or sodium benzoate; a flavor such as strawberry flavor or peppermint; or the like. [0031] 30 Further, for example, tablets, powders or granules, each of which is suitable for oral administration, can be formulated by adding: a saccharide such as lactose, sugar, glucose, sucrose, mannitol, or sorbitol; a starch such as that of potato, wheat, or corn; an inorganic substance such as calcium carbonate, 35 calcium sulfate, sodium hydrogen carbonate, or sodium chloride; 5 WO 2013/129700 PCT/JP2013/056204 a filler such as crystalline cellulose or plant powder like licorice root powder, gentian powder, or the like; a disintegrator such as starch, agar, gelatin powder, crystalline cellulose, carmellose sodium, carmellose calcium, calcium 5 carbonate, sodium hydrogen carbonate, or sodium alginate; a lubricant such as magnesium stearate, talc, hydrogenated plant oil, macrogol, or silicone oil; a binder such as polyvinyl alcohol, hydroxypropyl cellulose, methyl cellulose, ethyl cellulose, carmellose, gelatin, or starch paste; a surfactant lo such as a fatty acid ester; a plasticizer such as glycerol; or the like. [0032] Additives generally used in foods or drinks may be added to preparations suitable for oral administration, including: 15 sweeteners, colorants, preservatives, thickening stabilizers, antioxidant agents, coloring agents, bleaching agents, anti fungal agents, gum bases, bitter agents, enzymes, waxes, sour agents, seasonings, emulsifiers, reinforcing agents, manufacturing agents, flavors, spice extracts, or the like. 20 [0033] The preparation suitable for oral administration may be used as a food or drink for improving vision performance such as a health food, a functional food, a nutritional supplement food, or a food for specific health use; and these may be in an 25 unprocessed form or in such forms as a powdered food, a sheet shaped food, a bottled food, a canned food, a retort food, a capsule food, a tablet food, a liquid food, or a drinkable preparation. [00341 30 Suitable parenteral administration includes, for example, an injection that preferably contains a sterilized aqueous preparation containing alanylglutamine or a salt thereof, which is isotonic to the recipient's blood. In the case of an injection, for example, a solution for injection is prepared 35 using a carrier containing a salt solution, a glucose solution, 6 WO 2013/129700 PCT/JP2013/056204 or a mixture of a salt solution and a glucose solution, or the like. [0035] Further, also added to these parenteral preparations may 5 be one or more auxiliary components selected from the diluents, antiseptics, flavors, fillers, disintegrators, lubricants, binders, surfactants and plasticizers described in the examples of the oral preparations, and the like. [0036] lo In the compositions of the present invention, the concentration of alanylglutamine or a salt thereof is appropriately selected depending on the type of preparation, the effect expected by administration of the preparation, and the like, but, for example, the concentration in the case of an oral 15 preparation is usually 0.1 to 100% by weight as alanylglutamine or a salt thereof, preferably 0.5 to 70% by weight, and particularly preferably 1 to 50% by weight. [0037] The dose and the administration frequency of the 20 compositions of the present invention may vary depending on the dosing form, the age and body weight of the patient, and the nature or the severity of the symptoms to be treated, but in general, it is administered once to several times a day usually in an amount of 5 mg to 10,000 mg, preferably 50 mg to 5,000 mg, 25 more preferably 500 mg to 3,000 mg per day for an adult in terms of alanylglutamine or a salt thereof. The dosing period is not particularly limited, but is usually for 1 day to 1 year, preferably 2 weeks to 3 months. 30 EXAMPLES Example 1: Manufacturing of a Tablet Containing Alanylglutamine [0038] A mixture of 136.2 kg of alanylglutamine, 36.0 kg of microcrystalline cellulose, 6.6 kg of sucrose fatty acid ester, 35 1.2 kg of calcium phosphate, and 20.0 kg of [beta]-cyclodextrin 7 WO 2013/129700 PCT/JP2013/056204 are mixed using a conical blender (CB-1200 Blender, manufactured by Nihon Kansoki Co., Ltd.). The mixture obtained is compressed and molded to a tablet for of 250 mg with 8 mm of diameter under 10 kN of compression-molding pressure using a rotary compression 5 molding machine (VIRGO524SSlAY, manufactured by Kikusui Seisakusho Co., Ltd.). Example 2: Manufacturing of an Enteric Capsule Containing Alanylglutamine lo [0039] A mixture of 20 kg of the mixture produced in Example 1 and 0.2 kg of silicon dioxide are mixed and agitated. The mixture obtained is put into a capsule-filling machine to fill 20,000 tablets of gelatin Number 2 hard-capsules, and hard 15 capsules are obtained. The surfaces of the hard-capsules are coated with a zein solution using a High Coater HCT-48 (manufactured by Freund Corporation) to produce 20,000 enteric capsules. 20 Example 3: Manufacturing of an Enteric Tablet Containing Alanylglutamine [00401 The surfaces of the tablets produced in Example 1 are coated with a shellac solution using a High Coater HCT-48 25 (manufactured by Freund Corporation) to produce enteric tablets. Example 4: Manufacturing of a Beverage Containing Alanylglutamine [0041] 30 An amount of 1.28 kg of alanylglutamine, 3 kg of erythritol (manufactured by Nikken Kagaku Co., Ltd.), 0.05 kg of citric acid, 3 g of artificial sweetener, and 0.06 kg of flavor are stirred and dissolved in 50 L of water at a temperature of 70 0 C. After the pH of the solution is adjusted to 3.3 with 35 citric acid, the solution is sterilized using plate 8 WO 2013/129700 PCT/JP2013/056204 sterilization and filled into bottles. The bottles are sterilized using a pasteurizer, and thus a drink for enhancing vision performance is produced. 5 Example 5: Efficacy of L-alanyl-L-glutamine (AG) Ingestion on Vision Performance [00421 The purpose of this study was to examine the efficacy of L-alanyl-L-glutamine (AG) ingestion on sports vision, including 1o reaction time. Ten women (21.2±1.6 years; height: 177.8±8.7 cm; body mass: 73.5±8.0 kg), all basketball players, volunteered for this study. The study required subjects to first participate in a 40 minute basketball game. During one trial, subjects consumed only water (W), while during the other two trials subjects 15 consumed the AG supplement marketed as Sustamine mixed in water using either a low dose (1 g per 500 ml) (AG1) or high dose (2 g per 500 ml) (AG2) concentration. Other subjects where not allowed to consume water or AG (DHY). [0043] 20 Measurement of hand-eye reaction time was performed on the Dynavison D2 (Dynavision, Ontario Canada). Subjects were required to assume a comfortable athletic stance and stand at a distance from the board where they could easily reach all of the lights. The board height was adjusted so the LCD screen was 25 located just below eye level. Participants were told to fixate their gaze on the LCD screen in the middle of the board and to keep their focus there for the entirety of the experiment. During the assessment each subject pressed a light with their dominant side index finger on the board. When a second light 30 flashed (on the same line of the initial light, but on the non dominant side of her body), the subject removed her finger and pressed the new visual stimulus. The time necessary to recognize the new stimulus (new light lit until finger lifted from initial light) was recorded as visual reaction time, and the time it 35 took for the subject to move and press the newly lit light was 9 WO 2013/129700 PCT/JP2013/056204 recorded as the motor reaction time. The total time for both visual reaction and motor reaction was calculated as the physical reaction time. A total of eight attempts were performed. The average time for all eight attempts was recorded. 5 Results [0044] Visual reaction time (Figure 2) was significantly better following AG1 (p=0.
    0 1 4 ) compared to DHY (No water and no AG lo consumed during trial), and a trend toward a similar response (p=0.018) was noted between AG2 and DHY. However no significant differences were noted in the motor response (see Figure 3). The change in the physical reaction time (combined visual and motor differences) was significantly greater for AG1 compared to DHY 15 (p=0.032) . [0045] Ingestion of AG1 also enhanced visual reaction time. The ability to enhance visual reaction time with AG1 does appear to have important implication for athletic performance. 20 [0046] According to the present invention, a sports vision improving agent containing alanylglutamine or a salt thereof as an active ingredient can be provided. [0047] 25 This application is based on US patent application No. 13/407,578, the contents of which are incorporated in full herein. 10
    权利要求:
    Claims (7)
    [1] 1. A vision performance enhancing composition comprising alanylglutamine or a salt thereof as an active ingredient. 5
    [2] 2. A method of improving vision performance, comprising the step of administering an effective amount of alanylglutamine or a salt thereof to a subject in need. 2o
    [3] 3. A use of alanylglutamine or a salt thereof for producing a composition for enhancement of vision performance.
    [4] 4. Alanylglutamine or a salt thereof for enhancement of vision performance. 15
    [5] 5. The method of claim 2, wherein the alanylglutamine or salt thereof is administered in an amount of 5 mg or more and 10,000 mg or less per day. 20
    [6] 6. The method of claim 2, wherein the alanylglutamine or salt thereof is administered in an amount of 50 mg or more and 5,000 mg or less per day.
    [7] 7. The method of claim 2, wherein the alanylglutamine or salt 25 thereof is administered in an amount of 500 mg or more and 3,000 mg or less per day. 11
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    同族专利:
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    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    DE3206784C2|1982-02-25|1985-05-09|Pfrimmer & Co Pharmazeutische Werke Erlangen Gmbh, 8520 Erlangen|Glutamine-containing preparations for oral or intravenous administration|
    JPH0832717B2|1987-10-07|1996-03-29|味の素株式会社|Method for producing glutamine derivative|
    JP3473976B2|1992-10-29|2003-12-08|協和醗酵工業株式会社|Method for producing alanylglutamine|
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    BRPI0418858A|2004-06-08|2007-11-20|Paola Ammannati|enzymatic treatment of retinitis pigmentosa and pharmaceutical composition relevant to it in the form of a kit|
    US20100234308A1|2006-03-23|2010-09-16|Kyowa Hakko Kogyo Co., Ltd.|Wake-up remedy|
    WO2007119502A1|2006-03-23|2007-10-25|Kyowa Hakko Kogyo Co., Ltd.|Bowel movement remedy|
    WO2007108530A1|2006-03-23|2007-09-27|Kyowa Hakko Kogyo Co., Ltd.|Muscle fatigue remedy|ES2733123T3|2014-05-23|2019-11-27|Kyowa Hakko Bio Co Ltd|Methods and compositions for enhancing the ability to concentrate|
    WO2018026703A1|2016-08-01|2018-02-08|Filament Biosolutions Inc.|Methods of treating and preventing cancer treatment side effects|
    CN112516080A|2018-01-23|2021-03-19|盛元医药广州有限公司|Medicinal composition for eyes and preparation method and application thereof|
    CN110124057A|2019-06-06|2019-08-16|天津医科大学总医院|A kind of anti-tumor drug or pharmaceutical carrier of the cyclodextrin comprising glutamine modification|
    法律状态:
    2016-09-22| FGA| Letters patent sealed or granted (standard patent)|
    优先权:
    申请号 | 申请日 | 专利标题
    US13/407,578||2012-02-28||
    US13/407,578|US20130225684A1|2012-02-28|2012-02-28|Methods and compositions for enhancement of vision performance|
    PCT/JP2013/056204|WO2013129700A1|2012-02-28|2013-02-28|Methods and compositions for enhancement of vision performance|
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