JP7367978B2 - 組成物 - Google Patents
組成物 Download PDFInfo
- Publication number
- JP7367978B2 JP7367978B2 JP2019570931A JP2019570931A JP7367978B2 JP 7367978 B2 JP7367978 B2 JP 7367978B2 JP 2019570931 A JP2019570931 A JP 2019570931A JP 2019570931 A JP2019570931 A JP 2019570931A JP 7367978 B2 JP7367978 B2 JP 7367978B2
- Authority
- JP
- Japan
- Prior art keywords
- composition
- succinate
- nicotinamide
- choline
- brain
- Prior art date
- Legal status (The legal status 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 status listed.)
- Active
Links
- 239000000203 mixture Substances 0.000 title claims description 150
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 claims description 182
- 229960003966 nicotinamide Drugs 0.000 claims description 89
- 235000005152 nicotinamide Nutrition 0.000 claims description 89
- 239000011570 nicotinamide Substances 0.000 claims description 89
- 210000004556 brain Anatomy 0.000 claims description 69
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 claims description 55
- YOEWQQVKRJEPAE-UHFFFAOYSA-L succinylcholine chloride (anhydrous) Chemical compound [Cl-].[Cl-].C[N+](C)(C)CCOC(=O)CCC(=O)OCC[N+](C)(C)C YOEWQQVKRJEPAE-UHFFFAOYSA-L 0.000 claims description 55
- ZKHQWZAMYRWXGA-KQYNXXCUSA-J ATP(4-) Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O)[C@@H](O)[C@H]1O ZKHQWZAMYRWXGA-KQYNXXCUSA-J 0.000 claims description 54
- ZKHQWZAMYRWXGA-UHFFFAOYSA-N Adenosine triphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)C(O)C1O ZKHQWZAMYRWXGA-UHFFFAOYSA-N 0.000 claims description 54
- 229940120904 succinylcholine chloride Drugs 0.000 claims description 54
- -1 succinate anion Chemical class 0.000 claims description 50
- 230000037149 energy metabolism Effects 0.000 claims description 41
- 235000013361 beverage Nutrition 0.000 claims description 39
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 claims description 36
- DRBBFCLWYRJSJZ-UHFFFAOYSA-N N-phosphocreatine Chemical compound OC(=O)CN(C)C(=N)NP(O)(O)=O DRBBFCLWYRJSJZ-UHFFFAOYSA-N 0.000 claims description 30
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- 239000002243 precursor Substances 0.000 claims description 4
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- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 claims description 3
- JLEBZPBDRKPWTD-TURQNECASA-O N-ribosylnicotinamide Chemical group NC(=O)C1=CC=C[N+]([C@H]2[C@@H]([C@H](O)[C@@H](CO)O2)O)=C1 JLEBZPBDRKPWTD-TURQNECASA-O 0.000 claims description 3
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- BAWFJGJZGIEFAR-NNYOXOHSSA-N NAD zwitterion Chemical compound NC(=O)C1=CC=C[N+]([C@H]2[C@@H]([C@H](O)[C@@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 BAWFJGJZGIEFAR-NNYOXOHSSA-N 0.000 claims description 2
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- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 claims 1
- BOPGDPNILDQYTO-NNYOXOHSSA-N nicotinamide-adenine dinucleotide Chemical compound C1=CCC(C(=O)N)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]2[C@H]([C@@H](O)[C@@H](O2)N2C3=NC=NC(N)=C3N=C2)O)O1 BOPGDPNILDQYTO-NNYOXOHSSA-N 0.000 description 34
- 229960001231 choline Drugs 0.000 description 32
- 230000000694 effects Effects 0.000 description 32
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 24
- 238000000034 method Methods 0.000 description 21
- 150000001875 compounds Chemical class 0.000 description 20
- 150000003839 salts Chemical class 0.000 description 20
- ZDQYSKICYIVCPN-UHFFFAOYSA-L sodium succinate (anhydrous) Chemical compound [Na+].[Na+].[O-]C(=O)CCC([O-])=O ZDQYSKICYIVCPN-UHFFFAOYSA-L 0.000 description 20
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 16
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- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 16
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- QWJSAWXRUVVRLH-UHFFFAOYSA-M choline bitartrate Chemical compound C[N+](C)(C)CCO.OC(=O)C(O)C(O)C([O-])=O QWJSAWXRUVVRLH-UHFFFAOYSA-M 0.000 description 10
- 229960004874 choline bitartrate Drugs 0.000 description 10
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- ZKMDOYRDBAGOAD-UHFFFAOYSA-L butanedioate;2-hydroxyethyl(trimethyl)azanium Chemical compound C[N+](C)(C)CCO.C[N+](C)(C)CCO.[O-]C(=O)CCC([O-])=O ZKMDOYRDBAGOAD-UHFFFAOYSA-L 0.000 description 6
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- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 4
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- 239000001789 thuja occidentalis l. leaf oil Substances 0.000 description 1
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- 235000010215 titanium dioxide Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
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- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- 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 or pantothenic acid
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Description
前記ヒトにおいて、
- 脳エネルギー代謝を回復、維持及び/又は増強するため;
- 精神的及び身体的耐久性を回復、維持及び/又は増強するため;
- 認知機能を維持及び/又は増強するため;
- 不均衡、損傷又は減少した脳エネルギー代謝に関連する状態又は症状を処置するため又はその発生又は再発のリスクを減少させるため;
- 不均衡、損傷又は減少した脳エネルギー代謝に関連する認知障害を処置するため又はその発症のリスクを減少させるため。
前記ヒトにおいて、
- 脳エネルギー代謝を回復、維持及び/又は増強するため;
- 精神的及び身体的耐久性を回復、維持及び/又は増強するため;
- 認知機能を維持及び/又は増強するため;
- 不均衡な、損傷した、又は減少した脳エネルギー代謝に関連する状態又は症状の発生又は再発を治療又はそのリスクを減少させるため;
- 前記ヒトにおける不均衡な、損傷した、又は減少した脳エネルギー代謝に関連する認知障害を治療又はそのリスクを減少させるため;
ここで、この組み合わせが、広範囲の他の化合物(例えば、以下に記載されるような)を含む組成物の一部であるか、又はコリンカチオンを提供するコリンの塩、コハク酸(2-)アニオンを提供するコハク酸の塩、及び本明細書に記載されるようなニコチンアミン又はニコチンアミド誘導体を本質的に含む単独の組成物としてであるかにかかわらず、有益かつ安全である。
- DISUとNAMからなる組成物での処理は、対照と比較して228%の細胞内ATPレベルの有意な相乗的増加をもたらす(p<0.05)。組成物の影響(ΔATP=228%)は、個々の成分、DISU及びNAMの影響(ΔATP=142+14=156%)の合計よりもそれぞれ1.5倍大きかった。組成物の効果(ΔATP=228%)とDISU単独の効果(ΔATP=142%)の間には有意差がある(p<0.05)。したがって、本発明の組成物は、脳細胞におけるATP産生の改善に相乗的に有効である。
- DISUとニコチン酸の組成物で処理すると、細胞内ATP量は対照と比較して152.0%増加し(p<0.05)、組成物の効果(ΔATP=152%)とDISU単独の効果(ΔATP=142%)の間に有意差はない(p>0.05)。DISUとニコチン酸の個々の効果(ΔATP =142+1=143%)の合計は、組成物の効果(ΔATP=152%)の値と類似している。したがって、本組成物の化合物がATPの産生に及ぼす複合効果は非相乗的である。NAMとニコチン酸(ナイアシン)は、一般に類似の生物学的能力を有するビタミンB3ファミリーのメンバーと考えられているにもかかわらず、提示されたデータは、それらがDISUと組み合わされたときの脳細胞におけるATPの産生に対する効果が異なることを明確に示している。
- コハク酸ナトリウムとNAMと重酒石酸コリンの組成物による処理は、対照と比較して細胞内ATPレベルの146%の有意な相乗的増加をもたらした(p<0.05)。組成物の影響(ΔATP=146%)は、その個々の成分であるコハク酸ナトリウム、NAM、及び重酒石酸コリンの影響の合計(ΔATP=23+14+40=77%)の約1.8倍であった。このように、コハク酸ナトリウム、NAM、及び重酒石酸コリンの組成も、脳細胞のATP産生の改善に相乗的に有効であった。コハク酸塩とNAMを含む組成物中のコリンアニオンの存在がミトコンドリアにおけるATPの相乗的生成に重要であることを、データは示している。組成物「コハク酸ナトリウムとNAMと重酒石酸コリン」(ΔATP=146%)の効果と組成物「コハク酸ナトリウムとNAM」(ΔATP=42%)の効果の間には有意差がある(p<0.05)。従って、本質的にコハク酸アニオン、コリンカチオン、及びNAMを含む本発明の組成物は、脳細胞におけるATPの産生に相乗的に有効である。
- コハク酸アニオンとコリンカチオンの組合せの選択は、本発明の組成物の相乗効果のスケールのために重要である。脳細胞のATP産生に及ぼす効果において、組成物「DISUとNAM」と「コハク酸ナトリウムとNAMと重酒石酸コリン塩」の間に有意差がある(p<0.05)。組成物「DISU及びNAM」は、組成物においてコリンカチオン、コハク酸アニオン、及びNAMのモル濃度は同じであったにもかかわらず、「コハク酸ナトリウムとNAMと重酒石酸コリン」よりも約1.6倍有効であった。DISUはコリンアニオンとコハク酸カチオンの組合せについて、優れた代表例であることを示した。
- コハク酸ナトリウム及びNAMによる個別処理、又はその組成物による処理は、対照と比較して、それぞれ、細胞内ATP量の23%、31%、又は42%の非有意な増加をもたらす(p>0.05)。コハク酸ナトリウムとNAMの個々の効果の合計(ΔATP =23+31=54%)は、組成物の効果(ΔATP=42%)の値と比較して、類似しており、わずかに大きい。したがって、コハク酸ナトリウム及びNAMの組成物は、コハク酸アニオン、NAM、及びコリンカチオンを含む本発明の組成物とは明確に対照的である、脳細胞におけるATP産生に対して相乗的に効果的ではない。
Claims (13)
- コリンカチオン、二価コハク酸アニオン、及びニコチンアミド又はニコチンアミド誘導体を含む組成物:
ここで、
前記ニコチンアミド誘導体はニコチンアミドリボシドであり、
前記組成物中の前記コリンカチオン、前記二価コハク酸塩アニオン、及び前記ニコチンアミド又は前記ニコチンアミド誘導体のモル比は、2:1:0.01~2:1:10であり、
前記組成物は哺乳動物の脳細胞におけるニコチンアミドアデニンジヌクレオチド、アデノシン三リン酸、及びホスホクレアチンのレベルを増加させるために相乗的に有効である。 - 前記コリンカチオン及び前記二価コハク酸アニオンがジコリンコハク酸塩の形態で存在する、請求項1に記載の組成物。
- 前記組成物が水溶液である、請求項1又は2に記載の組成物。
- 前記ニコチンアミド又は前記ニコチンアミド誘導体が10mg~4000mgの量で存在する、請求項1~3のいずれかに記載の組成物。
- 前記ジコリンコハク酸塩が10mg~1000mgの量で存在する、請求項2~4のいずれかに記載の組成物。
- 前記組成物が栄養組成物である、請求項1~5のいずれかに記載の組成物。
- クレアチン及びその前駆体をさらに含む、請求項1~6のいずれかに記載の組成物: ここで、クレアチンの前駆体はグリシン又はアルギニンである。
- ヒトにおける脳エネルギー代謝の回復用、維持用、又は増強用の、請求項1~7のいずれかに記載の組成物。
- 前記ヒトが、加齢したヒト個体及び/又は心理的ストレス、疲労、不眠症又は精神的うつ病を有するか又はその影響を受けやすいヒト個体である、請求項8に記載の組成物。
- 前記組成物が、飲料、食品、医療用飲料、又は医療用食品として製剤化される、請求項1~9のいずれかに記載の組成物。
- 不均衡な、損傷した、又は減少した脳エネルギー代謝に関連する1つ以上の症状又は状態を有するヒトの食事管理用の、請求項6~9のいずれかに記載の組成物:
ここで、前記1つ以上の症状又は状態は、精神集中の欠如、精神的強度及び耐久性の低下、頻繁な気分変動、精神的抑うつ、季節性感情障害(SAD)、不眠、疲労、低下した認知能力、学習、及び記憶から選択される。 - 前記ヒトが、加齢したヒト個体又は心理的ストレスを有するか又はその影響を受けやすいヒト個体である、請求項11に記載の組成物。
- 前記組成物が、飲料、食品、医療用飲料、又は医療用食品として製剤化される、請求項11又は12に記載の組成物。
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GBGB1715214.1A GB201715214D0 (en) | 2017-09-20 | 2017-09-20 | A dietary composition comprising choline succinate salt (2:1) and nicotinamide, and nicotinamide riboside/or nicotinamide derivative |
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