WO2007142286A1 - 疲労軽減剤 - Google Patents
疲労軽減剤 Download PDFInfo
- Publication number
- WO2007142286A1 WO2007142286A1 PCT/JP2007/061522 JP2007061522W WO2007142286A1 WO 2007142286 A1 WO2007142286 A1 WO 2007142286A1 JP 2007061522 W JP2007061522 W JP 2007061522W WO 2007142286 A1 WO2007142286 A1 WO 2007142286A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- fatigue
- salt
- dartathione
- ortin
- reducing agent
- Prior art date
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- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 230000036544 posture Effects 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 235000013324 preserved food Nutrition 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 235000013772 propylene glycol Nutrition 0.000 description 1
- 230000000384 rearing effect Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000000284 resting effect Effects 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 229920002545 silicone oil Polymers 0.000 description 1
- 238000002791 soaking Methods 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 235000013599 spices Nutrition 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000000551 statistical hypothesis test Methods 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000012353 t test Methods 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical compound C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
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
- 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
- A23L33/17—Amino acids, peptides or proteins
- A23L33/175—Amino acids
-
- 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
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid, pantothenic acid
- A61K31/198—Alpha-aminoacids, e.g. alanine, edetic acids [EDTA]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/06—Tripeptides
- A61K38/063—Glutathione
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/02—Nutrients, e.g. vitamins, minerals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
Definitions
- the present invention relates to a fatigue-reducing agent containing ortine or a salt thereof and dartathione or a salt thereof as active ingredients.
- Orthine secretes growth hormone and enhances muscle synthesis, and is used as a food material to prevent obesity by increasing basal metabolism, mainly in the United States and Japan.
- Orthine is also used in Europe in the form of L-ortin L-asnoraginate as a medicine to improve liver damage.
- Non-patent Document 2 In morbid fatigue associated with an increase in blood ammonia level, administration of ortin or its salts is known to reduce blood ammonia level and recover from morbid fatigue (Patent Literature). 1-3, non-patent literature 1). It is also known that in healthy individuals, the subjective symptoms of fatigue are reduced by ingestion of ortin (Non-patent Document 2).
- Patent Document 1 Japanese Patent Publication No.42-7767
- Patent Document 2 Japanese Patent Publication No. 46-3194
- Patent Document 3 Japanese Patent Publication No. 41-8592
- Non-Patent Document 1 “Arzneim.- Forsch. (Drug Res.)”, 1970, No. 8, pl064- 1067
- Non-Patent Document 2 “Food and Development”, 2005, No. 40, No. 11, p62-64
- an object of the present invention is to provide a fatigue reducing agent. Means for solving the problem
- the present invention relates to the following (1) to (3).
- a fatigue reducing agent comprising ortine or a salt thereof and dartathione or a salt thereof as active ingredients.
- a method for reducing fatigue comprising administering an effective amount of ortin or a salt thereof and dartathione or a salt thereof to a subject in need thereof.
- a safe and effective fatigue reducing agent containing ortine or a salt thereof and dartathione or a salt thereof as an active ingredient can be provided.
- FIG. 1 is a graph showing the swimming time of rats depending on the breeding conditions. +, 1 indicates whether or not the rearmost column rearing condition is met. * Indicates that there is a significant difference at a risk rate of less than 5%.
- a force L-ortin which includes L-orthotine or D-ortin, is preferable.
- Oltin used in the present invention may be obtained by any production method.
- a chemical synthesis method [Coll.Czechoslov.Chem.
- L-orthine and D-orthine can be purchased from Sigma-Aldrich.
- salts of ortin include acid addition salts, metal salts, ammonium salts, organic amine addition salts, amino acid addition salts, and the like.
- Acid addition salts include inorganic salts such as hydrochloride, sulfate, nitrate, phosphate, acetate, Examples include organic acid salts such as oleate, fumarate, kenate, malate, lactate, a-ketoglutarate, darconate, and power prillate.
- Examples of the metal salt include alkali metal salts such as sodium salt and potassium salt, alkaline earth metal salts such as magnesium salt and strong salt, aluminum salt, zinc salt and the like.
- Ammonium salts include salts such as ammonia and tetramethyl ammonium.
- organic amine addition salt examples include salts of morpholine, piperidine and the like.
- amino acid addition salts include salts of glycine, ferrolanine, lysine, aspartic acid, dartamic acid, and the like.
- salts of ortin hydrochloride, citrate, malate, a-ketoglutarate, and aspartate are preferably used.
- Examples of the dartathione used in the present invention include reduced type dartathione and acid type dartathione.
- Reduced dartathione represents a tripeptide having a structure of ⁇ -L-Glu-L-Cys-Gly, and acid-dartathione represents a dartathione dipeptide in which two molecules of reduced dartathione are bound by an SS bond.
- the reduced type dartathione and the acid type dartathione used in the present invention may be obtained by any production method.
- Methods for producing reduced dartathione include extraction from microorganisms such as yeast [Methods in Enzymology, 3, 603 (1957)], chemical synthesis [Bull. Chem. Soc. Jpn., 53, 2529 (1980) ], Method such as Enzyme Method (JP-A 61-74595), etc.
- Examples of the method for producing 1S oxidized glutathione include [Acta Biochim. Pol., 17, 175 (1970)].
- the reduced type dartathion and the acid type dartathione can also be purchased from Sigma-Aldrich.
- the fatigue-reducing agent of the present invention may contain either the reduced type dartathione or the acid type dartathione alone, or may contain the reduced type dartathione and the acid type dartathione at the same time. Good.
- reduced dartathione and oxidized dartathion contained in the fatigue reducing agent of the present invention ONs may be present in the agent as their salts.
- the salt of reduced type dartathion and acid salt type dartathione include the same salts as the above-mentioned salts of ortin.
- a substance that is metabolized to reduced dartathione in vivo such as N-acetylcystein, can also be used in place of dartathione.
- composition ratio of ortin or a salt thereof and dartathione or a salt thereof in the fatigue relieving agent of the present invention is 1: 100 to 100: 1, preferably 1:50 to 50: 1, particularly preferably, by weight. 10: 1 ⁇ 1: 10.
- the fatigue reducing agent of the present invention may be prepared so that ortin or a salt thereof and dartathione or a salt thereof are contained in the same agent. It may be used as a kit or set form agent (hereinafter simply referred to as a kit).
- each agent contained in the kit or the like may be present in any state as long as it exists in a separate form.
- each agent may be packaged separately or mixed in the same container.
- each agent contained in a kit or the like is administered or ingested separately, it is desirable to administer it within the time when the active ingredient in each agent has high efficacy in the body. For example, for each administration or ingestion, all agents are administered or ingested within 8 hours, preferably within 2 hours.
- Fatigue can be reduced by administering or ingesting the fatigue reducing agent of the present invention.
- Fatigue includes physiological fatigue and pathological fatigue.
- Physiological fatigue means a defensive response to maintain human health. More specifically, it means fatigue that appears in daily activities such as work, housework, and leisure sports, and includes mental fatigue that is not just physical fatigue.
- pathological fatigue means heart disease, bronchial asthma, hepatitis, anemia, metabolic disease, muscle disease, various infectious diseases, fatigue that appears as symptoms associated with basic diseases such as cancer, and chronic fatigue symptoms group, mental It means fatigue in depression due to common causes and overtraining syndrome due to sports.
- the fatigue reducing agent of the present invention can be used for reducing any of the above fatigues.
- As the fatigue relieving agent of the present invention it is desirable to provide orthine or a salt thereof and dartathione or a salt thereof as usual in various formulations.
- the preparation contains ortin or a salt thereof and dartathione or a salt thereof as active ingredients, but may further contain any active ingredient.
- These preparations are produced by any method well known in the technical field of pharmaceutics by mixing the active ingredient with one or more pharmacologically acceptable carriers.
- the dosage form of the preparation is the most effective in reducing fatigue, and it is possible to increase oral administration or parenteral administration such as intravenous, intraperitoneal or subcutaneous administration. Oral administration is preferred.
- dosage forms to be administered include tablets, powders, granules, pills, suspensions, emulsions, soaking agents, decoction, capsules, syrups, solutions, elixirs, extracts, tinctures, fluid extracts, etc. Any of these oral preparations, injections, drops, creams, suppositories and the like can be used, but they are preferably used as oral preparations.
- Liquid preparations suitable for oral administration include water, sucrose, sorbitol, sugars such as fructose, Daricols such as polyethylene glycol, propylene glycol, sesame oil, olive oil, soybean oil, etc. Oils, p-hydroxybenzoates and other preservatives, para-benzoic acid derivatives such as methyl para-benzoate, preservatives such as sodium benzoate, and flavors such as strawberry flavor and peppermint. It can be formulated.
- tablets, powders and granules suitable for oral administration include sugars such as lactose, sucrose, bud sugar, sucrose, mannitol and sorbitol, starch such as potato, wheat and corn, carbonic acid Minerals such as calcium, calcium sulfate, sodium hydrogen carbonate, sodium chloride salt, plant powder such as crystalline cellulose, licorice powder, gentian powder, starch, agar, gelatin powder, crystalline cellulose, carmellose sodium, carme Disintegrants such as roast calcium, calcium carbonate, sodium bicarbonate, sodium alginate, etc., lubricants such as magnesium stearate, talc, hydrogenated vegetable oil, macrogol, silicone oil, polyvinylenorenoreconole, hydroxypropinoresenore Loin, Methino Resenolose, Ethino Resenore It can be formulated by adding a binder such as loin, carmellose, gelatin, starch paste, a surfact
- preparations suitable for oral administration include additives generally used in foods and drinks, such as sweeteners, colorants, preservatives, thickening stabilizers, antioxidants, color formers, bleaching agents, antibacterial agents. Molds, gum bases, bitters, enzymes, brighteners, acidulants, seasonings, emulsifiers, fortifiers, manufacturing agents, flavors, spice extracts, etc. may be added.
- Formulations suitable for oral administration are for reducing fatigue as they are or in the form of powdered foods, sheet foods, bottled foods, canned foods, retort foods, capsule foods, tablet foods, liquid foods, drinks, etc. It may also be used as food and drink such as health foods, functional foods, dietary supplements, and special health foods.
- Suitable for parenteral administration are also sterile aqueous solutions containing, for example, ortin or a salt thereof that is isotonic with the blood of the recipient, and dartathione or a salt thereof.
- a solution for injection is prepared using a carrier comprising a salt solution, a glucose solution, or a mixture of a salt solution and a glucose solution.
- parenteral agents one kind selected from preservatives, preservatives, excipients, disintegrating agents, lubricants, binders, surfactants, plasticizers and the like exemplified in the oral preparations. Or more auxiliary components can be added.
- the concentration of ortin or a salt thereof and dartathione or a salt thereof in the fatigue relieving agent of the present invention is appropriately selected according to the type of preparation, the effect expected by administration of the preparation, and the like.
- Orthine or a salt thereof and dartathione or a salt thereof are usually 0.1 to: LOO% by weight, preferably 0.5 to 70% by weight, particularly preferably 1 to 50% by weight.
- the dosage and number of administrations when administering the fatigue relieving agent of the present invention to humans vary depending on the administration form, the age, weight, etc. of the recipient, but per adult day, ortin or a salt thereof, and glutathione or the
- the salt is usually administered once to several times a day so as to be 50 mg to 30 g, preferably 100 mg to 10 g, particularly preferably 200 mg to 3 g.
- the administration period is not particularly limited, but is usually 1 day to 1 year, preferably 1 week to 3 months.
- the preparation of the present invention can be used for non-human animals (hereinafter abbreviated as non-human animals) other than humans.
- Non-human animals can include non-human animals such as mammals, birds, reptiles, amphibians and fish.
- the dose When administered to a non-human animal, the dose varies depending on the age, type, nature or severity of the animal body weight lkgl per day, ortin or its salt and dartathione or its salt, The dose is usually 1 mg to 600 mg, preferably 2 mg to 200 mg, more preferably 4 mg to 60 mg once a day!
- the administration period is not particularly limited, but is usually 1 day to 1 year, preferably 1 week to 3 months.
- Submerged breeding refers to breeding with water 1.5 cm deep in a plastic cage. Under this environment, it is impossible for rats that avoid water to take sufficient sleep and resting postures, and it is impossible to rest mentally and physically at all times. It is known that some animals die if they are kept under water for more than 7 days. Rats that have been in water for 5 days are said to be an animal model that leads to exhaustion due to fatigue. .
- swimming was performed with a weight equivalent to 8% of the body weight, and the time until the tip of the nose was submerged for 10 seconds or more was measured.
- a mixture obtained by mixing and stirring 20 kg of the mixture prepared in Example 1 and 0.2 kg of silicon dioxide was charged into a capsule filling machine, and filled into 20000 gelatin capsules made of gelatin to obtain hard capsules.
- the surface of the obtained node capsule is coated with a twein solution to produce 20000 enteric capsules.
- the surface of the tablet prepared in Example 1 is coated with shellac solution to produce an enteric tablet.
Abstract
Description
Claims
Priority Applications (5)
Application Number | Priority Date | Filing Date | Title |
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CN2007800210370A CN101460159B (zh) | 2006-06-07 | 2007-06-07 | 疲劳缓解剂 |
JP2008520613A JP5085541B2 (ja) | 2006-06-07 | 2007-06-07 | 疲労軽減剤 |
EP07744852A EP2050444B1 (en) | 2006-06-07 | 2007-06-07 | Fatigue-reducing agent |
AT07744852T ATE508740T1 (de) | 2006-06-07 | 2007-06-07 | Mittel zur verringerung von müdigkeit |
US12/303,613 US20100137226A1 (en) | 2006-06-07 | 2007-06-07 | Fatigue-reducing agent |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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JP2006158156 | 2006-06-07 | ||
JP2006-158156 | 2006-06-07 |
Publications (1)
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WO2007142286A1 true WO2007142286A1 (ja) | 2007-12-13 |
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PCT/JP2007/061522 WO2007142286A1 (ja) | 2006-06-07 | 2007-06-07 | 疲労軽減剤 |
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US (1) | US20100137226A1 (ja) |
EP (1) | EP2050444B1 (ja) |
JP (1) | JP5085541B2 (ja) |
CN (1) | CN101460159B (ja) |
AT (1) | ATE508740T1 (ja) |
WO (1) | WO2007142286A1 (ja) |
Cited By (8)
Publication number | Priority date | Publication date | Assignee | Title |
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WO2009107660A1 (ja) * | 2008-02-25 | 2009-09-03 | 味の素株式会社 | 糖尿病又は肥満病の予防又は治療剤 |
JP2013040142A (ja) * | 2011-08-18 | 2013-02-28 | Kyowa Hakko Bio Co Ltd | オルニチン含有組成物 |
JP2014159381A (ja) * | 2013-02-19 | 2014-09-04 | Kyowa Hakko Bio Co Ltd | オルニチン含有体組成改善用組成物 |
JP2015531341A (ja) * | 2012-09-28 | 2015-11-02 | 協和発酵バイオ株式会社 | グルタチオンを含有する免疫増強剤 |
JP2017008002A (ja) * | 2015-06-25 | 2017-01-12 | 株式会社東洋新薬 | 抗疲労剤 |
WO2018225482A1 (ja) * | 2017-06-07 | 2018-12-13 | 花王株式会社 | アンモニア代謝促進剤 |
JP2019194246A (ja) * | 2019-07-11 | 2019-11-07 | 株式会社東洋新薬 | 抗疲労剤 |
JP2021020881A (ja) * | 2019-07-30 | 2021-02-18 | 三菱商事ライフサイエンス株式会社 | 疲労回復剤 |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
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CN102552457A (zh) * | 2010-12-24 | 2012-07-11 | 漆又毛 | 一种氨基酸和提取物组合物的药物用途 |
CN102526750A (zh) * | 2012-01-06 | 2012-07-04 | 安徽黄山胶囊股份有限公司 | 一种植物结肠溶空心胶囊 |
WO2017004396A1 (en) * | 2015-06-30 | 2017-01-05 | Nucorplabs, Inc. | Chewable composition to deliver gsh |
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Also Published As
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JP5085541B2 (ja) | 2012-11-28 |
EP2050444A4 (en) | 2009-06-03 |
EP2050444A1 (en) | 2009-04-22 |
CN101460159B (zh) | 2011-11-23 |
US20100137226A1 (en) | 2010-06-03 |
CN101460159A (zh) | 2009-06-17 |
EP2050444B1 (en) | 2011-05-11 |
ATE508740T1 (de) | 2011-05-15 |
JPWO2007142286A1 (ja) | 2009-10-29 |
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