JP5931337B2 - 認知機能を高める組成物及び方法 - Google Patents
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- 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
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- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
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- A23K20/10—Organic substances
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- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
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- A23K50/00—Feeding-stuffs specially adapted for particular animals
- A23K50/40—Feeding-stuffs specially adapted for particular animals for carnivorous animals, e.g. cats or dogs
- A23K50/48—Moist feed
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- 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]
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- A—HUMAN NECESSITIES
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- 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
- A61K31/201—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 one or two double bonds, e.g. oleic, linoleic acids
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- 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
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- 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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
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- 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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
- A61K31/23—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of acids having a carboxyl group bound to a chain of seven or more carbon atoms
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- 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
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
- A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
- A61K31/355—Tocopherols, e.g. vitamin E
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- 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
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
- A61K31/375—Ascorbic acid, i.e. vitamin C; Salts thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/04—Sulfur, selenium or tellurium; Compounds thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/56—Materials from animals other than mammals
- A61K35/60—Fish, e.g. seahorses; Fish eggs
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/26—Psychostimulants, e.g. nicotine, cocaine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
Description
本明細書では以下の略語を使用し得る:MCT、中鎖トリグリセリド;AA、アラキドン酸;ALA、αリノレン酸;ANOVA、分散分析;DHA、ドコサへキサエン酸;DPA、ドコサペンタエン酸;EPA、エイコサペンタエン酸;LA、リノール酸;LCPUFA、長鎖ポリ不飽和脂肪酸(本明細書で使用する場合、LCPUFAは、1つ以上のこのような脂肪酸を称する);NO、酸化窒素;NORC、酸化窒素放出化合物(複数可);及びL−Arg、L−アルギニン。
(式中、R'、R''及びR'''は、グリセロール骨格にエステル化された炭素骨格中に5〜12個の炭素を有する脂肪酸である)。
本発明の脂質は、当技術分野で公知の任意の方法、例えば、直接エステル化、転位、分留、エステル交換等により調製できる。例えば、脂質は、植物油、例えば、ココナツ油の転位により調製できる。鎖長の長さ及び分布は、元の油に応じて変化し得る。例えば、C6を1〜10%、C8を30〜60%、C10を30〜60%、C10を1〜10%含有するMCTは、パーム油及びココナツ油に一般に由来する。R'、R''及びR'''で、C8を約95%超含有するMCTは、オクタン酸のグリセリンへの半合成エステル化により作製できる。全C8を約50%及び/又は全C10を約50%有するMCTを含む混合物も本明細書で有用である。前記MCT組成物の商業的供給源が利用でき、当業者に知られている。このようなMCTは、同じように挙動し、本明細書で使用する場合、MCTという用語内に包含される。
発明
動物及び試験群
認知的経験のあるビーグル犬48頭(7.5から11.6歳までの雄23頭及び雌25頭)を試験した。犬の平均年齢は9.38歳であった。適正にするために、犬は、位置遅延非位置合わせ課題(DNMP)及び特異性課題で訓練されたことを含め、少なくとも6ヶ月の事前の認知試験の経験を有していなければならなかった。
犬には、壁掛け式自動給水システム及び/又は水入れから自由に水を摂取させた。動物には、タンパク質32%、脂肪20%及び繊維3%程度を有する5種類の成犬用メンテナンスフードの内、1種類を1日1回与えた。最初の個々の食物量は、次式「kcal所要量=110kcal/日×(BW×0.75)」(式中、BWは体重である)を用いて計算した。該式は、適切な身体状態で一定の体重を維持することが意図されていた。
認知試験バッテリー
ランドマーク弁別学習(7〜99日)。自己中心的学習及び逆転(100〜163日)
この課題では、犬は、外部ランドマークと彼らの近さに基づき、2つの目的物の1つに接近するように訓練された。該課題は、空間内で目的物の場所を特定するために外部ランドマークの利用を伴う、他者中心的空間能力を評価することが意図されていた。犬を、より難しいタイプの同じ一般問題で引き続き試験した。
一般試験法:施行の開始時、犬に刺激トレーを差し出すために開き戸を開き、犬は、2つの同一の刺激物の内、1つを動かすことによって反応を示すために最大30秒が与えられた。犬が食物報酬を覆う刺激物を動かしたとき、正解反応としてカウントされた。犬が報酬なしの刺激物を動かしたとき、不正解としてカウントされた。動物は、63セッションにわたって、セッション毎に12回の試行を受けた。
ランドマーク試験結果
Claims (13)
- 動物の認知機能を高めるのに有効な量で、1つ以上の長鎖ポリ不飽和脂肪酸(LCPUFA)、1つ以上の中鎖トリグリセリド(MCT)及び1つ以上の酸化窒素放出化合物(NORC)を含む、老齢又は加齢動物の、加齢に伴い低下した認知機能を高める医薬組成物であって、
前記NORCがアルギニンであり、
認知機能を高めるのに有効な量で、1つ以上のビタミンB群及び1つ以上の抗酸化剤を含む、医薬組成物。 - 前記LCPUFAが、天然魚油、ALA、EPA、DPA、又はDHAの1つ若しくは複数を含む、請求項1に記載の医薬組成物。
- 0.1%〜50%のLCPUFAを含む、請求項1又は2に記載の医薬組成物。
- 1%〜30%のMCTを含む、請求項1〜4のいずれか一項に記載の医薬組成物。
- 0.1%〜20%のNORCを含む、請求項1〜5のいずれか一項に記載の医薬組成物。
- 推奨1日所要量の0.1〜40倍のビタミンB群を含む、請求項1に記載の医薬組成物。
- 推奨1日所要量の0.1〜25倍の抗酸化剤を含む、請求項1に記載の医薬組成物。
- 推奨1日所要量の0.1〜40倍のビタミンB群及び推奨1日所要量の0.1〜25倍の抗酸化剤を含む、請求項1に記載の医薬組成物。
- 認知機能を高めるのに有効な量で、1つ以上の認知に関する薬剤を更に含む、請求項1〜9のいずれか一項に記載の医薬組成物。
- ヒトを除く加齢又は老齢動物の、加齢に伴い低下した認知機能を高める方法であって、
前記動物の認知機能を高めるのに有効な量で、1つ以上の長鎖ポリ不飽和脂肪酸(LCPUFA)、1つ以上の中鎖トリグリセリド(MCT)及び1つ以上の酸化窒素放出化合物(NORC)を含む医薬組成物を前記動物に投与することを含み、
前記NORCがアルギニンであり、
前記医薬組成物が、認知機能を高めるのに有効な量で、1つ以上のビタミンB群及び1つ以上の抗酸化剤を含む、方法。 - 前記動物が加齢に伴う認知障害と関連する表現型を有し、
前記表現型が、前記表現型を有さない対照動物と比較したとき、想起力の低下、短期記憶喪失、学習速度の低下、学習能力の低下、問題解決能力の低下、注意持続時間の低下、運動能力の低下、意識障害の増加又は認知症、の1つ若しくは複数を含む、請求項11に記載の方法。 - 動物の認知機能を高めるのに有効な量で、1つ以上の長鎖ポリ不飽和脂肪酸(LCPUFA)、1つ以上の中鎖トリグリセリド(MCT)、1つ以上の酸化窒素放出化合物(NORC)、1つ以上のビタミンB群及び1つ以上の抗酸化剤を前記動物に投与することを含む、ヒトを除く加齢又は老齢動物の、加齢に伴い低下した認知機能を高めるための方法であって、
前記NORCがアルギニンである、方法。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US99766507P | 2007-10-04 | 2007-10-04 | |
US60/997,665 | 2007-10-04 | ||
PCT/US2008/011424 WO2009045481A1 (en) | 2007-10-04 | 2008-10-02 | Compositions and methods for enhancing cognitive function |
Publications (3)
Publication Number | Publication Date |
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JP2010540636A JP2010540636A (ja) | 2010-12-24 |
JP2010540636A5 JP2010540636A5 (ja) | 2011-11-17 |
JP5931337B2 true JP5931337B2 (ja) | 2016-06-08 |
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Application Number | Title | Priority Date | Filing Date |
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JP2010527993A Active JP5931337B2 (ja) | 2007-10-04 | 2008-10-02 | 認知機能を高める組成物及び方法 |
Country Status (16)
Country | Link |
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US (1) | US20100292330A1 (ja) |
EP (1) | EP2194781B2 (ja) |
JP (1) | JP5931337B2 (ja) |
CN (1) | CN101820754A (ja) |
AU (3) | AU2008307494B2 (ja) |
BR (1) | BRPI0818301B1 (ja) |
CA (1) | CA2701179C (ja) |
ES (1) | ES2664777T5 (ja) |
HU (1) | HUE037628T2 (ja) |
MX (1) | MX2010003568A (ja) |
NO (1) | NO2194781T3 (ja) |
PL (1) | PL2194781T5 (ja) |
RU (1) | RU2507742C2 (ja) |
TR (1) | TR201807131T4 (ja) |
WO (1) | WO2009045481A1 (ja) |
ZA (1) | ZA201003084B (ja) |
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CN101820754A (zh) | 2010-09-01 |
EP2194781A4 (en) | 2011-08-24 |
NO2194781T3 (ja) | 2018-07-21 |
AU2008307494A1 (en) | 2009-04-09 |
TR201807131T4 (tr) | 2018-06-21 |
EP2194781A1 (en) | 2010-06-16 |
ES2664777T3 (es) | 2018-04-23 |
US20100292330A1 (en) | 2010-11-18 |
EP2194781B2 (en) | 2021-03-24 |
BRPI0818301A2 (pt) | 2014-10-07 |
AU2016202685B2 (en) | 2017-09-21 |
WO2009045481A1 (en) | 2009-04-09 |
AU2008307494B2 (en) | 2013-09-05 |
MX2010003568A (es) | 2010-04-21 |
CA2701179A1 (en) | 2009-04-09 |
BRPI0818301B1 (pt) | 2022-02-15 |
CA2701179C (en) | 2021-03-16 |
PL2194781T5 (pl) | 2021-11-15 |
RU2010117221A (ru) | 2011-11-10 |
PL2194781T3 (pl) | 2018-07-31 |
AU2016202685A1 (en) | 2016-05-19 |
JP2010540636A (ja) | 2010-12-24 |
AU2013205916B2 (en) | 2016-05-19 |
EP2194781B1 (en) | 2018-02-21 |
AU2013205916A1 (en) | 2013-06-06 |
ES2664777T5 (es) | 2021-10-25 |
HUE037628T2 (hu) | 2018-09-28 |
RU2507742C2 (ru) | 2014-02-27 |
ZA201003084B (en) | 2011-10-26 |
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