WO2019150497A1 - 認識機能向上剤 - Google Patents
認識機能向上剤 Download PDFInfo
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- WO2019150497A1 WO2019150497A1 PCT/JP2018/003245 JP2018003245W WO2019150497A1 WO 2019150497 A1 WO2019150497 A1 WO 2019150497A1 JP 2018003245 W JP2018003245 W JP 2018003245W WO 2019150497 A1 WO2019150497 A1 WO 2019150497A1
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Classifications
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Definitions
- the present invention relates to a cognitive function improver that improves brain function, particularly cognitive function.
- Examples of brain functions that improve learning ability include recognition function and information processing ability.
- the inventor has eagerly searched for a new cognitive function improver that enhances the cognitive function and the information processing ability in order to enhance the learning ability.
- One embodiment of the present disclosure is a cognitive function improver having 6-methylsulfinylhexyl isothiocyanate. Another aspect of the present disclosure is a cognitive function improving agent having a wasabi extract.
- the cognitive function improver according to an embodiment of the present disclosure has 6-methylsulfinylhexyl isothiocyanate (abbreviation: 6-MSITC).
- 6-MSITC used in the present disclosure can be obtained by a chemical synthesis method, but may be extracted and purified from a plant.
- the plant include, for example, Bataceae, Brassicaceae, Bretschneideraceae, Capparaceae, Caraceacee, Euceae family, and Euceae family. ), Limnanthaceae, Moringaceae, Pentadiplandracae, Phytolacaceae, Pittospoaceae, R A family (Tovariaceae), Nouzenharen family (Tropaeolaceae), mention may be made of the plant or the like.
- wasabi (Wasabija japonica) [aka: Wasabi], horseradish (Armorica rusticana) [aka: Wasabi], Batis maritima (Japanese name unknown), mustard (Brassica juncea), broccoli Bra oleracea var.italica), Arabidopsis thaliana, solouna (Capsella bursa-pastoris), watercress (Nasturium officinalis), Bretschneidera sinisis (upper cirque) ii (unknown Japanese name); Putranjiva roxburghii (unknown Japanese name), Tersonia brevipes (unknown Japanese name), Limnanthes douglasii (unknown Japanese name), Wasabikino (Moringa oleiferazent) americana), Bursaris spinosa var.
- 6-MSITC incana (Japanese name unknown), cynomolgus seizou (Reseda alba), Salvadora persica (Japanese name unknown), Tovaria pendula (Japanese name unknown), nasturtium (Tropaeolum majus) and the like.
- 6-MSITC that can be used in the present disclosure is not limited to those obtained from the above-mentioned plants, and all natural resources containing 6-MSITC can be used as raw materials.
- Examples of the method for extracting and purifying 6-MSITC include a method for extracting 6-MSITC from a cruciferous plant wasabi and horseradish. Details of the extraction method are disclosed in Japanese Patent No. 3919489.
- 6-MSITC may be extracted or synthesized from wasabi.
- the chemical synthesis method of 6-MSITC will be specifically described as follows. In principle, it follows the method of Kjaer et al. (Kjaer et al., Acta chem .. Scand., 11, 1298, 1957). 6-Chlorohexanol is used and refluxed with CH 3 -SNa to give 6-methylthiohexanol. This is reacted with thionyl chloride (SOCl 2 ) to obtain 6-chlorohexylmethyl sulfide.
- SOCl 2 thionyl chloride
- an amino group is introduced with phthalimide potassium salt to produce N- (6-methylthiohexyl) -phthalimide. Hydrazine hydrate is added thereto and refluxed to obtain 6-methylthiohexylamine, and then thiocarbonyl chloride is reacted to obtain 6-methylthiohexyl isothiocyanate.
- 6-methylthiohexyl isothiocyanate is oxidized with m-chloroperbenzoic acid to oxidize the methylthio group to obtain 6-methylsulfinylhexyl isothiocyanate (6-MSITC) (Morimitsu et. Al., J. Biol). Chem., 277, 3456, 2002).
- a wasabi extract may be used for the recognition function improving agent of the present disclosure.
- the wasabi extract may contain 6-MSITC.
- the dosage of the cognitive function-enhancing agent of the present disclosure is determined by taking into account the patient's age, sex, weight, usage, dosage and the like. Examples of usage include oral administration.
- the daily dose of 6-MSITC in the cognitive function-improving agent is preferably 0.01 mg / day to 10 mg / day, more preferably 0.05 mg / day to 5.0 mg / day. 1 mg / day to 1 mg / day is desirable.
- wasabi extract When wasabi extract is used as a cognitive function improver, the wasabi extract is ingested so that the daily dose of 6-MSTIC in the wasabi extract is 0.01 mg / day to 10 mg / day. Good.
- the cognitive function improver of the present disclosure may be contained in foods, cosmetics, quasi drugs, or functional indication foods / specific health foods.
- the food of the present disclosure may contain a recognition function improving agent.
- the cosmetic of the present disclosure may include a recognition function improving agent.
- the quasi-drug of the present disclosure may contain a recognition function improving agent.
- the form of the food containing the recognition function improving agent of the present disclosure is arbitrary and not limited.
- Specific food forms include, for example, general foods, general drinks, supplements, health foods, functional indication foods, foods for specified health use and foods for specific uses, soft drinks, tea drinks, drinks And alcoholic beverages such as wine, confectionery, cooked rice, breads, noodles, side dishes, and seasonings.
- cosmetics and quasi-drugs containing the recognition function improver of the present disclosure are arbitrary and are not limited.
- Specific cosmetics and quasi drugs include, for example, internal / external preparations, lotions, emulsions, creams, ointments, packs, skin cleansers, shampoos, rinses, bath preparations, and the like.
- dosage forms of cosmetics and quasi-drugs containing the recognition function improving agent of the present disclosure are not limited.
- Specific dosage forms of cosmetics and quasi drugs include, for example, capsules, tablets, powders, granules, liquids, emulsions, creams, gels, ointments, sheets, mousses and the like.
- the cognitive function improver of the present disclosure includes various optional components generally used in foods, cosmetics, and quasi-drugs as subcomponents in addition to 6-MISTC, which is the main component, as long as the effects of the present disclosure are not impaired. You may mix
- test substances were prepared, and the effects on brain function when administered to humans were investigated.
- the test substances are Sample 1 and Reference Sample 1.
- Sample 1 consists of wasabi extract with 6-MSITC, cyclodextrin, gelatin, and caramel pigment.
- the content of 6-MSITC in Sample 1 is 0.5 mg.
- Reference sample 1 is the same as sample 1 except that it does not contain wasabi extract.
- the form of the sample 1 and the reference sample 1 is powder.
- test substance was ingested by subjects who did not exercise, and the effect on brain function was investigated.
- subjects who do not have exercise habits subjects who did not exercise regularly more than twice a week and once for 30 minutes or more were included in the survey.
- the test subjects were ingested as follows and the test subjects were investigated.
- the test subjects are men and women aged 45 to 69 who have no exercise habits. All subjects are aware of forgetfulness but are healthy.
- the intake period was 8 weeks.
- Antioxidant action, blood flow improving action, anti-inflammatory action, and skin condition improving effect have been reported in human tests in which 0.2-1.0 mg of 6-MSTIC is ingested by humans. . Therefore, the content of 6-MSITC in Sample 1 was set to 0.5 mg.
- the STROP test is a test for evaluating the ability to identify and process two different pieces of information (language information and color vision information) that enter the brain simultaneously.
- the test was performed according to the test procedure of the new Stroop test (Yuji Hakoda, Megumi Watanabe; New Stroop Test II, Toyo Physical Co., Ltd.).
- This test consists of sub-tests of four steps (“step 1”, “2”, “3”, “4”), and the difficulty increases as the steps progress.
- the test involves multiple questions. The subject solves the problem within a predetermined time. For each step, the number of achievements, the number of correct answers, the number of incorrect answers (number of errors), the reverse Stroop interference rate, and the Stroop interference rate were evaluated.
- the number of achievements means the processing speed to solve the problem.
- the number of correct answers is a numerical value corresponding to the number of correctly answered questions.
- the number of wrong answers is a numerical value corresponding to the number of wrong questions.
- the reverse Stroop interference rate and the Stroop interference rate were obtained by the following calculation formulas.
- Step 1 Check the ink color that the word represents
- Step 2 The color that the word represents does not correspond to the ink color.
- Step 3 Select the words that correspond to the ink colors and check them.
- Step 4 The color represented by the words does not correspond to the color of the ink. Select and check the word that corresponds to the color of the ink on which the word is written.
- the number of achievements is shown in Table 1
- the number of correct answers is shown in Table 2
- the number of incorrect answers is shown in Table 3
- the interference rate is shown in Table 4.
- “measured value” indicates an actually measured value
- “change amount” is a value obtained by subtracting a value before intake from a value at 4th or 8th week.
- Step 1 Number of Achievements Step 1 was the amount of change at the 8th week, and the A group (6-MSITC intake group) increased significantly compared with the P group (6-MSITC non-taker group). Also in step 4, the A group significantly increased compared to the P group with the amount of change at the 8th week. In steps 2 and 3, there was no significant difference between groups in the amount of change at the time of examination.
- the P group is in the 8th week in Step 1
- the A group is in the 4th and 8th weeks
- the P group is in Step 2.
- the A group increased significantly at 8th week, in Step 3
- both groups increased in the 8th week, and in Step 4, only the A group increased in the 8th week.
- Step 1 Number of correct answers
- Step 4 the A group significantly increased compared to the P group at the change amount at the 8th week.
- steps 2 and 3 there was no significant difference between groups in the amount of change at all examination points.
- the P group is in the 8th week in Step 1
- the A group is in the 4th and 8th weeks
- the P group is in Step 2.
- the A group increased significantly at 8th week, in Step 3
- both groups increased in the 8th week, and in Step 4, only the A group increased in the 8th week.
- Step 1 Number of wrong answers
- the change amount at the 4th week is 0.2 ⁇ 0.4 for the P group
- the A group ⁇ 0.2 ⁇ 0.4
- the change amount at the 8th week is 0.1% for the P group They were ⁇ 0.2 and Group A-0.2 ⁇ 0.4.
- steps 2, 3, and 4 there was no significant difference between groups in the amount of change at all examination points.
- Burdue Pegboard Inspection is an inspection to evaluate the skill of manual work such as assembly and packaging (Purdue research Foundation (no date). Puerdue Peg-board Tes. Lafayette, lafayette Instrument Co.) ). In this inspection, a Bardue pegboard (A929-1, manufactured by Sakai Medical Co., Ltd.) was used according to the procedure manual, and the reverse Stroop interference rate and the Stroop interference rate were calculated. The test was performed once for each of the right hand, left hand, and both hands. Table 5 shows the transition of measured values and the amount of change from before intake for the dominant hand, non-dominant hand, and both hands. An increase in the measured value indicates an improvement.
- the dominant hand is 8 weeks in both groups
- the non-dominant hand is the 8th week only in the A group
- both hands are the 8th week in the P group
- the 4th week in the A group Increased significantly in the eyes.
- RAVLT Ray Auditory Language Learning Test
- RAVLT Zaak M. D., Rezac Neuropsychological Examination Collection 2005, Creation Publishing
- 15 words (list A) that are semantically irrelevant are presented audibly, and immediately after that, the words are reproduced.
- the same trial is performed five times (from the first trial to the fifth trial).
- 15 words (list B) different from list A were answered in the same way, and then words still remembered from list A were verbally answered (sixth trial: memory after interference task) ).
- the following tests (2) to (5) were performed as interference tasks, and after 20 minutes, the words still remembered in the list A were verbally answered (seventh trial: delayed reproduction).
- short-term memory was evaluated from the number of achievements STM (Short Term Memory) of the first trial.
- the total immediate memory was evaluated by the total number TIM (Total Immediate memory) of the number of achievements from the first trial to the fifth trial.
- the language learning ability was evaluated by a value VLA (Verbal Learning Ability) obtained by subtracting the achievement number of the first trial from the achievement number of the fifth trial.
- the value of RI (Retroactive Interference Effect) obtained by subtracting the number of achievements of the sixth trial from the number of achievements of the fifth trial divided by the number of achievements of the fifth trial. It was evaluated whether or not the memory was lost or the recall was hindered.
- Tables 6 and 7 show the changes in measured values and the amount of change from before intake for the differences between trials 1 to 7, list B, STM, TIM, VLA, RI, trial 7 and trial 6. Indicated.
- Step 3 the A group was significantly improved as compared with the P group. Although there was no significant difference between the groups at the 8th week, the number of wrong answers in the A group was lower than that in the P group.
- the Stroop test is thought to be able to measure both attention function and information processing speed, and the improvement in the “number of achievements” and “number of correct answers” in Steps 1 and 4 of the Stroop test is not a routine exercise habit and forgetfulness. This suggests that ingestion of 6-MSITC-containing foods to middle-aged and elderly men and women who are aware of this situation may improve the discrimination / processing ability (attention function), which is part of cognitive function.
- Cognitive functions include various functions such as memory function, language, action, visual and visuospatial recognition, attention, executive function, decision making, facial expression and emotional reaction, although a clear definition has not yet been established.
- Toshio Yamauchi et al. Handbook for Evaluation of Mental and Psychological Functions, Nakayama Shoten, 2015.
- attention is not a single function, but it closely supports the activities of learning, memory, performance, and working memory, so it is an important part of the evaluation of cognitive function (Kazuhiro Shinozaki, Motomi Satomi, Mental illness and cognitive function, Emerging Medical Publishers, 2009: 55-61).
- 6-MSITC has been reported to have antioxidant and anti-inflammatory effects by inhibiting the production of active oxygen, and has also been reported to improve anti-platelet aggregation, blood circulation such as blood flow and blood vessels (Naoki Kinae, Furugun Michiyo, Kojima Osamu, Wasabi All, Academic Publishing Center, 2006). It is considered that these actions by 6-MSITC may contribute to improving the function of the central nervous system by suppressing cell damage.
- the anti-platelet aggregation action was examined using human platelets, and it has been reported that 6-MSITC contained in the wasabi extract exhibits an aggregation inhibitory activity about 20 times stronger than aspirin.
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Abstract
Description
発明者は、学習能力を高めるために、認識機能及び情報処理能力を高める新たな認識機能向上剤を鋭意探求した。
本開示の別の一態様は、わさび抽出物を有する認識機能向上剤である。
原理的にはKjaer等の方法に従う(Kjaer等, Acta chem.. Scand., 11, 1298, 1957)。6-クロロヘキサノールを用い、CH3-SNaと還流して6-メチルチオヘキサノールを得る。これに塩化チオニル(SOCl2)を作用させて、6-クロロヘキシルメチルサルファイドを得る。次にガブリエル法を用いて、フタルイミドカリウム塩により、アミノ基を導入し、N-(6-メチルチオヘキシル)-フタルイミドを生成する。これにヒドラジン水和物を加えて還流し、6-メチルチオヘキシルアミンを得た後、チオカルボニルクロライドを作用させて、6-メチルチオヘキシルイソチオシアネートを得る。
本開示の認識機能向上剤の投与量は、患者の年齢、性別、体重、用法、用量などを考慮することにより決定される。用法としては、経口投与などが挙げられる。経口投与の場合、認識機能向上剤における6-MSITCの1日あたりの投与量は0.01mg/日~10mg/日がよく、更に0.05mg/日~5.0mg/日が好ましく、0.1mg/日~1mg/日が望ましい。
本開示の食品は、認識機能向上剤を含んでいてもよい。本開示の化粧品は、認識機能向上剤を含んでいてもよい。本開示の医薬部外品は、認識機能向上剤を含んでいてもよい。
(1)被験物質の調製
被験物質は、試料1及び参考試料1である。試料1は、6-MSITCを有するわさび抽出物、シクロデキストリン、ゼラチン、及びカラメル色素からなる。試料1における6-MSITCの含有量は0.5mgである。参考試料1は、わさび抽出物を含んでいない点を除いて、試料1と同様である。試料1及び参考試料1の形態は、パウダーである。
一般に運動などの身体活動により認知機能の改善及び低下の抑制が認められることは知られている(安永明智,木村憲,高齢者の認知機能と運動・身体活動の関係,第25回健康医科学研究助成論文集,2010:129-13611)Yanagisawa H.et.al.,Acute moderate exercise elicits increased dorsolateral prefrontal activation and improves cognitive performance with Stroop test.,Neuroimage.,2010,50(4):1702-1710)。本実施例でも、運動習慣の有無が各種神経心理学的検査に影響を与えることが予想された。
6-MSTICをヒトに0.2~1.0mg摂取させたときのヒト試験において、抗酸化作用、血流改善作用、抗炎症作用、肌状態改善効果が報告されている(金印株式会社)。そこで、試料1における6-MSITCの含有量は0.5mgとした。
(2-1)Stroop試験
Stroop試験は、脳へ同時に入ってくる2つの異なる情報(言語情報と色覚情報)の識別・処理能力を評価するテストである。新Stroop検査(箱田裕司、渡辺めぐみ;新ストループ検査II、株式会社トーヨーフィジカル)の検査実施手順に従って行った。このテストは、4つのステップ(「ステップ1」、「2」、「3」、「4」)のサブテストからなり、ステップが進むに従って難易度が増す。テストは複数の問題を含む。被験者は、所定時間内に問題を解く。それぞれのステップについて、達成数、正答数、誤答数(誤数)、逆ストループ干渉率、ストループ干渉率を評価した。
ストループ干渉率(%)=100×(ステップ3の正答数―ステップ4の正答数)÷ステップ3の正答数
達成数、正答数は測定値の増加が改善を示す。誤答数(誤数)、逆ストループ干渉率、ストループ干渉率は測定値の低下が改善を示す。
ステップ1:言葉が表すインクの色にチェックをつける
ステップ2:言葉の表す色とインクの色とが対応していない。言葉が表すインクの色にチェックをつける。
ステップ3:インクの色に当たる言葉を選んでチェックをつける。
ステップ4:言葉の表す色とインクの色とが対応していない。言葉が書かれているインクの色に当たる言葉を選んでチェックをつける。
ステップ1は、8週目の変化量で、A群(6-MSITC摂取者群)はP群(6-MSITC非摂取者群)と比べて有意に増加した。ステップ4においても、8週目の変化量で、A群はP群と比べて有意に増加した。ステップ2,3はすべて検査時点で変化量に有意な群間差はなかった。
ステップ1では、8週目の変化量で、A群がP群と比べて有意に増加した。ステップ4では、8週目の変化量で、A群がP群と比べて有意に増加した。ステップ2,3はすべての検査時点で変化量に有意な群間差はなかった。
ステップ1において、4週目の変化量はP群0.2±0.4、A群-0.2±0.4、8週目の変化量はP群0.1±0.2、A群-0.2±0.4であった。ステップ2,3,4はすべての検査時点で変化量に有意な群間差はなかった。
逆ストループ干渉率では、4週目の変化量で、P群がA群に比べて有意に数値が低かった。摂取前値において、P群と比べてA群が有意に低かったため、摂取前値を共変量として共分散分析を行った。その結果、P群とA群との間に有意な群間差は見られなかった。ストループ干渉率は4週目の変化量に有意な群間差はなかった。
バーデュー・ペグボード検査は、組立や梱包などの手作業に対する巧緻性を評価する検査(Purdue research Foundation (no date). Puerdue Peg-board Tes. Lafayette, lafayette Instrument Co.)である。本検査では、バーデュー・ペグボード(A929-1, 酒井医療社製)を用いて手順書に従って実施し、逆ストループ干渉率及びストループ干渉率を計算した。右手、左手、両手の順に、それぞれ1回ずつ実施した。利き手、非利き手、両手について、測定値の推移と、摂取前からの変化量とを表5に示した。測定値の増加が改善を示す。
RAVLT(Lezak M. D., レザック 神経心理学的検査集成 2005, 創造出版)は、即時的な記憶と短時間の記憶の容量並びにその保持・再生能力を評価するテストである。意味的に無関連な15語(リストA)について聴覚的に提示し、直後にその単語を再生させる。同様の試行を5回行う(第1試行から第5試行)。その後に、リストAとは異なる15語(リストB)を同様の方法で回答させ、さらにその後にリストAのうちまだ覚えている単語を口頭で回答させた(第6試行:干渉課題後の記憶)。更に干渉課題として以下の(2)~(5)の各検査を実施し、20分後にリストAのうちまだ覚えている単語を口頭で回答させた(第7試行:遅延再生)。
第2試行については、4週目の変化量(P群1.0土1.8個、A群2.2士1.6個)で、A群がP群と比べて有意に増加した。摂取前値において、P群と比べてA群が有意に低かったため、摂取前値を共変量として共分散分析を行った。その結果、P群とA群との間に有意な群間差は見られなかった。
Stroop試験では、ステップ1,4の「達成数」、「正答数」について、8週目の変化量で、A群(6-MSITC摂取者群)がP群(6-MSITC非摂取者群)に比べて有意な改善がみられた。
Stroop試験は、注意機能・情報処理速度の両面を測定できると考えられており、Stroop試験のステップ1、4の「達成数」、「正答数」の改善は、日常的な運動習慣がなく物忘れを自覚する中高齢男女に6-MSITC含有食品を摂取させると、認知機能の一部である識別・処理能力(注意機能)が向上する可能性を示唆する。明確な定義はいまだ定まってはいないものの、認知機能は、記憶機能をはじめ、言語、行為、視覚・視空間認知、注意、遂行機能、意思決定、表情・情動反応など、様々な機能を含むものとして知られている(山内俊雄ら,精神・心理機能評価ハンドブック,中山書店,2015)。特に注意は単一の機能ではなく、学習、記憶、遂行機能及び作業記憶の活動を密接に支えていることからも、認知機能評価の中で重要な位置づけにある(篠崎和弘,辻富基美,精神疾患と認知機能,新興医学出版社,2009:55-61)。これまでの研究から、加齢による認知機能の衰えは、注意を要する課題及び情報処理速度を要する課題で起こりやすいことが報告されている(Chodzko-Zajko W J.and Moore K.A.,Physical Fitness and Cognitive Functioning in Aging.,Exercise and Sport Sciences Reviews,1994,22(1):195-200、Hawkins H.L.,Kramer A.F. and Capaldi D.,Aging,exercise,and attention. Psychology and Aging,1992,7(4):643-653))。これら過去の研究から考えると、本実験において6-MSITC含有食品について注意機能向上効果が示唆されたのは、重要な知見と言える。
Claims (8)
- 6-メチルスルフィニルヘキシルイソチオシアネートを有する認識機能向上剤。
- 1日当たりの6-メチルスルフィニルヘキシルイソチオシアネートの摂取量が0.05mg/日~5.0mg/日である請求項1に記載の認識機能向上剤。
- 上記6-メチルスルフィニルヘキシルイソチオシアネートがわさびから抽出または合成されたものである請求項1の認識向上剤。
- わさび抽出物を有する認識機能向上剤。
- 請求項1~4のいずれかに記載の認識機能向上剤を含む食品。
- 請求項1~4のいずれかに記載の認識機能向上剤を含む化粧品。
- 請求項1~4のいずれかに記載の認識機能向上剤を含む医薬部外品。
- 請求項1~4のいずれかに記載の認識機能向上剤を含む機能性表示食品又は特定保健用食品。
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JP2019568484A JP6671706B2 (ja) | 2018-01-31 | 2018-01-31 | 認識機能向上剤 |
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KR1020207025148A KR102406690B1 (ko) | 2018-01-31 | 2018-01-31 | 인식기능 향상제 |
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EP18903772.4A EP3747431A4 (en) | 2018-01-31 | 2018-01-31 | MEANS OF IMPROVING RECOGNITION |
US16/965,252 US20210069146A1 (en) | 2018-01-31 | 2018-01-31 | Recognition ability improving agent |
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JP7126300B1 (ja) | 2022-03-30 | 2022-08-26 | 金印株式会社 | 背外側前頭前野の血流増加剤、背外側前頭前野の活性化剤、背外側前頭前野の血流増加のための食品、及び背外側前頭前野を活性化させるための食品 |
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- 2018-01-31 EP EP18903772.4A patent/EP3747431A4/en active Pending
- 2018-01-31 US US16/965,252 patent/US20210069146A1/en active Pending
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- 2018-01-31 CN CN201880087397.9A patent/CN111629722A/zh active Pending
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Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
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JP7126300B1 (ja) | 2022-03-30 | 2022-08-26 | 金印株式会社 | 背外側前頭前野の血流増加剤、背外側前頭前野の活性化剤、背外側前頭前野の血流増加のための食品、及び背外側前頭前野を活性化させるための食品 |
WO2023190733A1 (ja) * | 2022-03-30 | 2023-10-05 | 金印株式会社 | 背外側前頭前野の血流増加剤、背外側前頭前野の活性化剤、背外側前頭前野の血流増加のための食品、及び背外側前頭前野を活性化させるための食品 |
JP2023148824A (ja) * | 2022-03-30 | 2023-10-13 | 金印株式会社 | 背外側前頭前野の血流増加剤、背外側前頭前野の活性化剤、背外側前頭前野の血流増加のための食品、及び背外側前頭前野を活性化させるための食品 |
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KR20200116483A (ko) | 2020-10-12 |
CN111629722A (zh) | 2020-09-04 |
JP6671706B2 (ja) | 2020-03-25 |
EP3747431A1 (en) | 2020-12-09 |
EP3747431A4 (en) | 2021-11-17 |
KR102406690B1 (ko) | 2022-06-07 |
JPWO2019150497A1 (ja) | 2020-04-02 |
US20210069146A1 (en) | 2021-03-11 |
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