JP6272766B2 - 認知の改善 - Google Patents
認知の改善 Download PDFInfo
- Publication number
- JP6272766B2 JP6272766B2 JP2014539897A JP2014539897A JP6272766B2 JP 6272766 B2 JP6272766 B2 JP 6272766B2 JP 2014539897 A JP2014539897 A JP 2014539897A JP 2014539897 A JP2014539897 A JP 2014539897A JP 6272766 B2 JP6272766 B2 JP 6272766B2
- Authority
- JP
- Japan
- Prior art keywords
- composition
- vitamin
- per
- subject
- uridine
- 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.)
- Expired - Fee Related
Links
- 230000007370 cognitive improvement Effects 0.000 title description 2
- 239000000203 mixture Substances 0.000 claims description 157
- DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 claims description 89
- MBMBGCFOFBJSGT-KUBAVDMBSA-N all-cis-docosa-4,7,10,13,16,19-hexaenoic acid Chemical compound CC\C=C/C\C=C/C\C=C/C\C=C/C\C=C/C\C=C/CCC(O)=O MBMBGCFOFBJSGT-KUBAVDMBSA-N 0.000 claims description 66
- 238000012360 testing method Methods 0.000 claims description 51
- 235000020669 docosahexaenoic acid Nutrition 0.000 claims description 42
- JAZBEHYOTPTENJ-JLNKQSITSA-N all-cis-5,8,11,14,17-icosapentaenoic acid Chemical compound CC\C=C/C\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O JAZBEHYOTPTENJ-JLNKQSITSA-N 0.000 claims description 41
- 229960005135 eicosapentaenoic acid Drugs 0.000 claims description 41
- JAZBEHYOTPTENJ-UHFFFAOYSA-N eicosapentaenoic acid Natural products CCC=CCC=CCC=CCC=CCC=CCCCC(O)=O JAZBEHYOTPTENJ-UHFFFAOYSA-N 0.000 claims description 41
- 235000020673 eicosapentaenoic acid Nutrition 0.000 claims description 41
- DRTQHJPVMGBUCF-PSQAKQOGSA-N beta-L-uridine Natural products O[C@H]1[C@@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-PSQAKQOGSA-N 0.000 claims description 40
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 claims description 40
- DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 claims description 40
- 229940045145 uridine Drugs 0.000 claims description 40
- DJJCXFVJDGTHFX-UHFFFAOYSA-N Uridinemonophosphate Natural products OC1C(O)C(COP(O)(O)=O)OC1N1C(=O)NC(=O)C=C1 DJJCXFVJDGTHFX-UHFFFAOYSA-N 0.000 claims description 39
- DJJCXFVJDGTHFX-XVFCMESISA-N uridine 5'-monophosphate Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(O)=O)O[C@H]1N1C(=O)NC(=O)C=C1 DJJCXFVJDGTHFX-XVFCMESISA-N 0.000 claims description 39
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 claims description 36
- 229940090949 docosahexaenoic acid Drugs 0.000 claims description 33
- LXNHXLLTXMVWPM-UHFFFAOYSA-N pyridoxine Chemical compound CC1=NC=C(CO)C(CO)=C1O LXNHXLLTXMVWPM-UHFFFAOYSA-N 0.000 claims description 32
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 31
- 208000010877 cognitive disease Diseases 0.000 claims description 24
- 229960001231 choline Drugs 0.000 claims description 23
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 claims description 23
- 230000019771 cognition Effects 0.000 claims description 23
- YUFFSWGQGVEMMI-JLNKQSITSA-N (7Z,10Z,13Z,16Z,19Z)-docosapentaenoic acid Chemical compound CC\C=C/C\C=C/C\C=C/C\C=C/C\C=C/CCCCCC(O)=O YUFFSWGQGVEMMI-JLNKQSITSA-N 0.000 claims description 22
- 235000021294 Docosapentaenoic acid Nutrition 0.000 claims description 22
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 claims description 22
- 208000024827 Alzheimer disease Diseases 0.000 claims description 21
- 229930003779 Vitamin B12 Natural products 0.000 claims description 21
- AGVAZMGAQJOSFJ-WZHZPDAFSA-M cobalt(2+);[(2r,3s,4r,5s)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2r)-1-[3-[(1r,2r,3r,4z,7s,9z,12s,13s,14z,17s,18s,19r)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2 Chemical compound [Co+2].N#[C-].[N-]([C@@H]1[C@H](CC(N)=O)[C@@]2(C)CCC(=O)NC[C@@H](C)OP(O)(=O)O[C@H]3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)\C2=C(C)/C([C@H](C\2(C)C)CCC(N)=O)=N/C/2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O AGVAZMGAQJOSFJ-WZHZPDAFSA-M 0.000 claims description 21
- 235000019152 folic acid Nutrition 0.000 claims description 21
- 239000011724 folic acid Substances 0.000 claims description 21
- 235000019163 vitamin B12 Nutrition 0.000 claims description 21
- 239000011715 vitamin B12 Substances 0.000 claims description 21
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 claims description 19
- 229960000304 folic acid Drugs 0.000 claims description 19
- 150000003904 phospholipids Chemical class 0.000 claims description 19
- 229930003427 Vitamin E Natural products 0.000 claims description 18
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 claims description 18
- 235000019165 vitamin E Nutrition 0.000 claims description 18
- 239000011709 vitamin E Substances 0.000 claims description 18
- 229940046009 vitamin E Drugs 0.000 claims description 18
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 claims description 16
- 229930003268 Vitamin C Natural products 0.000 claims description 16
- 230000001149 cognitive effect Effects 0.000 claims description 16
- 229940067631 phospholipid Drugs 0.000 claims description 16
- RADKZDMFGJYCBB-UHFFFAOYSA-N pyridoxal hydrochloride Natural products CC1=NC=C(CO)C(C=O)=C1O RADKZDMFGJYCBB-UHFFFAOYSA-N 0.000 claims description 16
- 235000019158 vitamin B6 Nutrition 0.000 claims description 16
- 239000011726 vitamin B6 Substances 0.000 claims description 16
- 235000019154 vitamin C Nutrition 0.000 claims description 16
- 239000011718 vitamin C Substances 0.000 claims description 16
- 229940011671 vitamin b6 Drugs 0.000 claims description 16
- 235000020660 omega-3 fatty acid Nutrition 0.000 claims description 13
- 201000011240 Frontotemporal dementia Diseases 0.000 claims description 12
- BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical compound [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 claims description 12
- UHDGCWIWMRVCDJ-ZAKLUEHWSA-N cytidine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-ZAKLUEHWSA-N 0.000 claims description 12
- 239000011669 selenium Substances 0.000 claims description 12
- 229910052711 selenium Inorganic materials 0.000 claims description 12
- 235000011649 selenium Nutrition 0.000 claims description 12
- UHDGCWIWMRVCDJ-UHFFFAOYSA-N 1-beta-D-Xylofuranosyl-NH-Cytosine Natural products O=C1N=C(N)C=CN1C1C(O)C(O)C(CO)O1 UHDGCWIWMRVCDJ-UHFFFAOYSA-N 0.000 claims description 11
- UHDGCWIWMRVCDJ-PSQAKQOGSA-N Cytidine Natural products O=C1N=C(N)C=CN1[C@@H]1[C@@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-PSQAKQOGSA-N 0.000 claims description 11
- 208000027061 mild cognitive impairment Diseases 0.000 claims description 11
- 229940012843 omega-3 fatty acid Drugs 0.000 claims description 11
- 229940035893 uracil Drugs 0.000 claims description 11
- MXHRCPNRJAMMIM-SHYZEUOFSA-N 2'-deoxyuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 MXHRCPNRJAMMIM-SHYZEUOFSA-N 0.000 claims description 10
- MXHRCPNRJAMMIM-UHFFFAOYSA-N desoxyuridine Natural products C1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 MXHRCPNRJAMMIM-UHFFFAOYSA-N 0.000 claims description 10
- 206010027175 memory impairment Diseases 0.000 claims description 10
- DVSZKTAMJJTWFG-SKCDLICFSA-N (2e,4e,6e,8e,10e,12e)-docosa-2,4,6,8,10,12-hexaenoic acid Chemical compound CCCCCCCCC\C=C\C=C\C=C\C=C\C=C\C=C\C(O)=O DVSZKTAMJJTWFG-SKCDLICFSA-N 0.000 claims description 9
- GZJLLYHBALOKEX-UHFFFAOYSA-N 6-Ketone, O18-Me-Ussuriedine Natural products CC=CCC=CCC=CCC=CCC=CCC=CCCCC(O)=O GZJLLYHBALOKEX-UHFFFAOYSA-N 0.000 claims description 9
- KAUVQQXNCKESLC-UHFFFAOYSA-N docosahexaenoic acid (DHA) Natural products COC(=O)C(C)NOCC1=CC=CC=C1 KAUVQQXNCKESLC-UHFFFAOYSA-N 0.000 claims description 9
- 239000006014 omega-3 oil Substances 0.000 claims description 9
- 206010012289 Dementia Diseases 0.000 claims description 8
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 claims description 8
- 201000002832 Lewy body dementia Diseases 0.000 claims description 7
- 201000004810 Vascular dementia Diseases 0.000 claims description 7
- 150000001720 carbohydrates Chemical class 0.000 claims description 7
- 235000014633 carbohydrates Nutrition 0.000 claims description 7
- 150000002632 lipids Chemical class 0.000 claims description 7
- 201000006417 multiple sclerosis Diseases 0.000 claims description 7
- 208000028698 Cognitive impairment Diseases 0.000 claims description 6
- 208000009829 Lewy Body Disease Diseases 0.000 claims description 6
- 208000018642 Semantic dementia Diseases 0.000 claims description 6
- 229940087168 alpha tocopherol Drugs 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 230000006996 mental state Effects 0.000 claims description 4
- 208000024891 symptom Diseases 0.000 claims description 4
- 229960000984 tocofersolan Drugs 0.000 claims description 4
- 235000004835 α-tocopherol Nutrition 0.000 claims description 4
- 239000002076 α-tocopherol Substances 0.000 claims description 4
- 150000002148 esters Chemical class 0.000 claims description 3
- 238000010984 neurological examination Methods 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 3
- 238000007689 inspection Methods 0.000 claims 2
- 230000008447 perception Effects 0.000 claims 2
- 230000003796 beauty Effects 0.000 claims 1
- 239000000470 constituent Substances 0.000 claims 1
- 238000000034 method Methods 0.000 description 22
- 230000000694 effects Effects 0.000 description 15
- 229940079593 drug Drugs 0.000 description 13
- 239000003814 drug Substances 0.000 description 13
- 239000000047 product Substances 0.000 description 12
- 230000003111 delayed effect Effects 0.000 description 11
- 235000014113 dietary fatty acids Nutrition 0.000 description 10
- 229930195729 fatty acid Natural products 0.000 description 10
- 239000000194 fatty acid Substances 0.000 description 10
- 150000004665 fatty acids Chemical class 0.000 description 10
- 235000018102 proteins Nutrition 0.000 description 9
- 108090000623 proteins and genes Proteins 0.000 description 9
- 102000004169 proteins and genes Human genes 0.000 description 9
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 8
- 230000006870 function Effects 0.000 description 8
- 239000012263 liquid product Substances 0.000 description 8
- 230000008449 language Effects 0.000 description 7
- 239000007788 liquid Substances 0.000 description 7
- 210000004556 brain Anatomy 0.000 description 6
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 6
- 230000003920 cognitive function Effects 0.000 description 6
- 230000006872 improvement Effects 0.000 description 6
- 238000003860 storage Methods 0.000 description 6
- 230000008859 change Effects 0.000 description 5
- -1 lipid lipid Chemical class 0.000 description 5
- 238000005259 measurement Methods 0.000 description 5
- 230000003557 neuropsychological effect Effects 0.000 description 5
- 238000011282 treatment Methods 0.000 description 5
- 206010003694 Atrophy Diseases 0.000 description 4
- 235000021342 arachidonic acid Nutrition 0.000 description 4
- 229940114079 arachidonic acid Drugs 0.000 description 4
- 230000037444 atrophy Effects 0.000 description 4
- 230000004153 glucose metabolism Effects 0.000 description 4
- 230000000007 visual effect Effects 0.000 description 4
- GHOKWGTUZJEAQD-ZETCQYMHSA-N (D)-(+)-Pantothenic acid Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-ZETCQYMHSA-N 0.000 description 3
- 108010064539 amyloid beta-protein (1-42) Proteins 0.000 description 3
- 230000003930 cognitive ability Effects 0.000 description 3
- XEEYBQQBJWHFJM-UHFFFAOYSA-N iron Substances [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 3
- 238000002595 magnetic resonance imaging Methods 0.000 description 3
- 230000006386 memory function Effects 0.000 description 3
- 235000021281 monounsaturated fatty acids Nutrition 0.000 description 3
- 230000002265 prevention Effects 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 239000010902 straw Substances 0.000 description 3
- 230000002123 temporal effect Effects 0.000 description 3
- 210000003478 temporal lobe Anatomy 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 229940088594 vitamin Drugs 0.000 description 3
- 229930003231 vitamin Natural products 0.000 description 3
- 235000013343 vitamin Nutrition 0.000 description 3
- 239000011782 vitamin Substances 0.000 description 3
- 230000001755 vocal effect Effects 0.000 description 3
- 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 2
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerol Natural products OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- HOKKHZGPKSLGJE-GSVOUGTGSA-N N-Methyl-D-aspartic acid Chemical compound CN[C@@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-GSVOUGTGSA-N 0.000 description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 2
- XCCTYIAWTASOJW-XVFCMESISA-N Uridine-5'-Diphosphate Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(=O)OP(O)(O)=O)O[C@H]1N1C(=O)NC(=O)C=C1 XCCTYIAWTASOJW-XVFCMESISA-N 0.000 description 2
- 229930003270 Vitamin B Natural products 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000032683 aging Effects 0.000 description 2
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 2
- 238000012093 association test Methods 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 235000013361 beverage Nutrition 0.000 description 2
- 239000000090 biomarker Substances 0.000 description 2
- 230000017531 blood circulation Effects 0.000 description 2
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- CYQFCXCEBYINGO-IAGOWNOFSA-N delta1-THC Chemical compound C1=C(C)CC[C@H]2C(C)(C)OC3=CC(CCCCC)=CC(O)=C3[C@@H]21 CYQFCXCEBYINGO-IAGOWNOFSA-N 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- 235000015872 dietary supplement Nutrition 0.000 description 2
- ADEBPBSSDYVVLD-UHFFFAOYSA-N donepezil Chemical compound O=C1C=2C=C(OC)C(OC)=CC=2CC1CC(CC1)CCN1CC1=CC=CC=C1 ADEBPBSSDYVVLD-UHFFFAOYSA-N 0.000 description 2
- 235000006694 eating habits Nutrition 0.000 description 2
- 235000019197 fats Nutrition 0.000 description 2
- 235000021323 fish oil Nutrition 0.000 description 2
- 229940014144 folate Drugs 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- ASUTZQLVASHGKV-JDFRZJQESA-N galanthamine Chemical compound O1C(=C23)C(OC)=CC=C2CN(C)CC[C@]23[C@@H]1C[C@@H](O)C=C2 ASUTZQLVASHGKV-JDFRZJQESA-N 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 210000004326 gyrus cinguli Anatomy 0.000 description 2
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 2
- 229910052742 iron Inorganic materials 0.000 description 2
- 150000002535 isoprostanes Chemical class 0.000 description 2
- 239000000787 lecithin Substances 0.000 description 2
- 229940067606 lecithin Drugs 0.000 description 2
- 235000010445 lecithin Nutrition 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- 235000020665 omega-6 fatty acid Nutrition 0.000 description 2
- 229940033080 omega-6 fatty acid Drugs 0.000 description 2
- 230000001936 parietal effect Effects 0.000 description 2
- 239000011574 phosphorus Substances 0.000 description 2
- 229910052698 phosphorus Inorganic materials 0.000 description 2
- 238000002600 positron emission tomography Methods 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 235000003441 saturated fatty acids Nutrition 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 230000001953 sensory effect Effects 0.000 description 2
- 238000002603 single-photon emission computed tomography Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- KYMBYSLLVAOCFI-UHFFFAOYSA-N thiamine Chemical compound CC1=C(CCO)SCN1CC1=CN=C(C)N=C1N KYMBYSLLVAOCFI-UHFFFAOYSA-N 0.000 description 2
- 235000019156 vitamin B Nutrition 0.000 description 2
- 239000011720 vitamin B Substances 0.000 description 2
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- PZNPLUBHRSSFHT-RRHRGVEJSA-N 1-hexadecanoyl-2-octadecanoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[C@@H](COP([O-])(=O)OCC[N+](C)(C)C)COC(=O)CCCCCCCCCCCCCCC PZNPLUBHRSSFHT-RRHRGVEJSA-N 0.000 description 1
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 description 1
- TWJNQYPJQDRXPH-UHFFFAOYSA-N 2-cyanobenzohydrazide Chemical compound NNC(=O)C1=CC=CC=C1C#N TWJNQYPJQDRXPH-UHFFFAOYSA-N 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- CKTSBUTUHBMZGZ-ULQXZJNLSA-N 4-amino-1-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-tritiopyrimidin-2-one Chemical compound O=C1N=C(N)C([3H])=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 CKTSBUTUHBMZGZ-ULQXZJNLSA-N 0.000 description 1
- AUNGANRZJHBGPY-MBNYWOFBSA-N 7,8-dimethyl-10-[(2R,3R,4S)-2,3,4,5-tetrahydroxypentyl]benzo[g]pteridine-2,4-dione Chemical compound OC[C@H](O)[C@H](O)[C@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-MBNYWOFBSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- RZCPXIZGLPAGEV-DCOIXEBESA-N 8,12-iso-ipf2alpha-vi Chemical compound CCCCC/C=C\C[C@H]([C@@H](C[C@@H]1O)O)[C@H]1/C=C/C(CCCC(O)=O)O RZCPXIZGLPAGEV-DCOIXEBESA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- GHOKWGTUZJEAQD-UHFFFAOYSA-N Chick antidermatitis factor Natural products OCC(C)(C)C(O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 229940122041 Cholinesterase inhibitor Drugs 0.000 description 1
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 208000031124 Dementia Alzheimer type Diseases 0.000 description 1
- 206010067889 Dementia with Lewy bodies Diseases 0.000 description 1
- 235000011201 Ginkgo Nutrition 0.000 description 1
- 241000218628 Ginkgo Species 0.000 description 1
- 235000008100 Ginkgo biloba Nutrition 0.000 description 1
- 229930186217 Glycolipid Natural products 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- FFFHZYDWPBMWHY-VKHMYHEASA-N L-homocysteine Chemical compound OC(=O)[C@@H](N)CCS FFFHZYDWPBMWHY-VKHMYHEASA-N 0.000 description 1
- 102000004895 Lipoproteins Human genes 0.000 description 1
- 108090001030 Lipoproteins Proteins 0.000 description 1
- PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 description 1
- ZOKXTWBITQBERF-UHFFFAOYSA-N Molybdenum Chemical compound [Mo] ZOKXTWBITQBERF-UHFFFAOYSA-N 0.000 description 1
- 235000021360 Myristic acid Nutrition 0.000 description 1
- TUNFSRHWOTWDNC-UHFFFAOYSA-N Myristic acid Natural products CCCCCCCCCCCCCC(O)=O TUNFSRHWOTWDNC-UHFFFAOYSA-N 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 235000021314 Palmitic acid Nutrition 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- XSVMFMHYUFZWBK-NSHDSACASA-N Rivastigmine Chemical compound CCN(C)C(=O)OC1=CC=CC([C@H](C)N(C)C)=C1 XSVMFMHYUFZWBK-NSHDSACASA-N 0.000 description 1
- JZRWCGZRTZMZEH-UHFFFAOYSA-N Thiamine Natural products CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N JZRWCGZRTZMZEH-UHFFFAOYSA-N 0.000 description 1
- FPIPGXGPPPQFEQ-BOOMUCAASA-N Vitamin A Natural products OC/C=C(/C)\C=C\C=C(\C)/C=C/C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-BOOMUCAASA-N 0.000 description 1
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 description 1
- 229930003448 Vitamin K Natural products 0.000 description 1
- 239000005862 Whey Substances 0.000 description 1
- 102000007544 Whey Proteins Human genes 0.000 description 1
- 108010046377 Whey Proteins Proteins 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- ZLRVWFDVJWKAIL-LXMACRGBSA-M [2,2-dimethyl-3-[(2r,3e)-3-oxidoiminobutan-2-yl]azanidylpropyl]-[(2r,3e)-3-hydroxyiminobutan-2-yl]azanide;oxotechnetium-99(3+) Chemical compound [99Tc+3]=O.O/N=C(\C)[C@@H](C)[N-]CC(C)(C)C[N-][C@H](C)C(\C)=N\[O-] ZLRVWFDVJWKAIL-LXMACRGBSA-M 0.000 description 1
- PGAVKCOVUIYSFO-UHFFFAOYSA-N [[5-(2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate Chemical compound OC1C(O)C(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)OC1N1C(=O)NC(=O)C=C1 PGAVKCOVUIYSFO-UHFFFAOYSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 230000004308 accommodation Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 description 1
- 210000004727 amygdala Anatomy 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 238000011952 auditory verbal learning test Methods 0.000 description 1
- OGBUMNBNEWYMNJ-UHFFFAOYSA-N batilol Chemical class CCCCCCCCCCCCCCCCCCOCC(O)CO OGBUMNBNEWYMNJ-UHFFFAOYSA-N 0.000 description 1
- 231100000871 behavioral problem Toxicity 0.000 description 1
- 230000002146 bilateral effect Effects 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 230000003925 brain function Effects 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000005018 casein Substances 0.000 description 1
- BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 description 1
- 235000021240 caseins Nutrition 0.000 description 1
- 229940106189 ceramide Drugs 0.000 description 1
- 150000001783 ceramides Chemical class 0.000 description 1
- 230000001055 chewing effect Effects 0.000 description 1
- 239000000544 cholinesterase inhibitor Substances 0.000 description 1
- 229910052804 chromium Inorganic materials 0.000 description 1
- 239000011651 chromium Substances 0.000 description 1
- 230000003931 cognitive performance Effects 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- IERHLVCPSMICTF-XVFCMESISA-N cytidine 5'-monophosphate Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(O)=O)O1 IERHLVCPSMICTF-XVFCMESISA-N 0.000 description 1
- 229940104302 cytosine Drugs 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000000378 dietary effect Effects 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 229960003530 donepezil Drugs 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 238000000537 electroencephalography Methods 0.000 description 1
- 210000001353 entorhinal cortex Anatomy 0.000 description 1
- 230000001667 episodic effect Effects 0.000 description 1
- 210000003617 erythrocyte membrane Anatomy 0.000 description 1
- 235000012041 food component Nutrition 0.000 description 1
- 235000021588 free fatty acids Nutrition 0.000 description 1
- 229960003980 galantamine Drugs 0.000 description 1
- ASUTZQLVASHGKV-UHFFFAOYSA-N galanthamine hydrochloride Natural products O1C(=C23)C(OC)=CC=C2CN(C)CCC23C1CC(O)C=C2 ASUTZQLVASHGKV-UHFFFAOYSA-N 0.000 description 1
- ZXQYGBMAQZUVMI-GCMPRSNUSA-N gamma-cyhalothrin Chemical compound CC1(C)[C@@H](\C=C(/Cl)C(F)(F)F)[C@H]1C(=O)O[C@H](C#N)C1=CC=CC(OC=2C=CC=CC=2)=C1 ZXQYGBMAQZUVMI-GCMPRSNUSA-N 0.000 description 1
- 230000000971 hippocampal effect Effects 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- FYYHWMGAXLPEAU-OUBTZVSYSA-N magnesium-25 atom Chemical compound [25Mg] FYYHWMGAXLPEAU-OUBTZVSYSA-N 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 229910052748 manganese Inorganic materials 0.000 description 1
- 239000011572 manganese Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- BUGYDGFZZOZRHP-UHFFFAOYSA-N memantine Chemical compound C1C(C2)CC3(C)CC1(C)CC2(N)C3 BUGYDGFZZOZRHP-UHFFFAOYSA-N 0.000 description 1
- 229960004640 memantine Drugs 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 229910052750 molybdenum Inorganic materials 0.000 description 1
- 239000011733 molybdenum Substances 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 1
- 238000010855 neuropsychological testing Methods 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 238000011903 nutritional therapy Methods 0.000 description 1
- 230000000050 nutritive effect Effects 0.000 description 1
- 235000021032 oily fish Nutrition 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 230000036542 oxidative stress Effects 0.000 description 1
- 229940055726 pantothenic acid Drugs 0.000 description 1
- 235000019161 pantothenic acid Nutrition 0.000 description 1
- 239000011713 pantothenic acid Substances 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 1
- SHUZOJHMOBOZST-UHFFFAOYSA-N phylloquinone Natural products CC(C)CCCCC(C)CCC(C)CCCC(=CCC1=C(C)C(=O)c2ccccc2C1=O)C SHUZOJHMOBOZST-UHFFFAOYSA-N 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 230000008433 psychological processes and functions Effects 0.000 description 1
- 229960004136 rivastigmine Drugs 0.000 description 1
- 150000004671 saturated fatty acids Chemical class 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000008347 soybean phospholipid Substances 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 230000009747 swallowing Effects 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 235000019157 thiamine Nutrition 0.000 description 1
- 229960003495 thiamine Drugs 0.000 description 1
- 239000011721 thiamine Substances 0.000 description 1
- 239000011573 trace mineral Substances 0.000 description 1
- 235000013619 trace mineral Nutrition 0.000 description 1
- 238000012034 trail making test Methods 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- 125000005457 triglyceride group Chemical group 0.000 description 1
- 230000016776 visual perception Effects 0.000 description 1
- 235000019155 vitamin A Nutrition 0.000 description 1
- 239000011719 vitamin A Substances 0.000 description 1
- QYSXJUFSXHHAJI-YRZJJWOYSA-N vitamin D3 Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C\C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-YRZJJWOYSA-N 0.000 description 1
- 235000005282 vitamin D3 Nutrition 0.000 description 1
- 239000011647 vitamin D3 Substances 0.000 description 1
- 235000019168 vitamin K Nutrition 0.000 description 1
- 239000011712 vitamin K Substances 0.000 description 1
- 150000003721 vitamin K derivatives Chemical class 0.000 description 1
- 229940045997 vitamin a Drugs 0.000 description 1
- 229940033158 vitamin b6 1 mg Drugs 0.000 description 1
- 229940021056 vitamin d3 Drugs 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 229940046010 vitamin k Drugs 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Images
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
- A23L33/115—Fatty acids or derivatives thereof; Fats or oils
- A23L33/12—Fatty acids or derivatives thereof
-
- 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
- A23L33/13—Nucleic acids or derivatives thereof
-
- 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
- A23L5/00—Preparation or treatment of foods or foodstuffs, in general; Food or foodstuffs obtained thereby; Materials therefor
-
- 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
- A61K31/13—Amines
- A61K31/14—Quaternary ammonium compounds, e.g. edrophonium, choline
-
- 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
-
- 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
-
- 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
-
- 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
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4415—Pyridoxine, i.e. Vitamin B6
-
- 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
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- 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
- A61K31/66—Phosphorus compounds
- A61K31/683—Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols
-
- 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
- A61K31/66—Phosphorus compounds
- A61K31/683—Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols
- A61K31/685—Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols one of the hydroxy compounds having nitrogen atoms, e.g. phosphatidylserine, lecithin
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
- A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
- A61K31/7068—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
- A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
- A61K31/7068—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
- A61K31/7072—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7135—Compounds containing heavy metals
- A61K31/714—Cobalamins, e.g. cyanocobalamin, i.e. vitamin B12
-
- 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
-
- 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
-
- 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
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
- A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Food Science & Technology (AREA)
- Nutrition Science (AREA)
- Polymers & Plastics (AREA)
- Mycology (AREA)
- Inorganic Chemistry (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Biochemistry (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Neurosurgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
a.ドコサヘキサエン酸(DHA)、エイコサペンタエン酸(EPA)、及びドコサペンタエン酸(DPA)からなる群より選択される1つ以上のオメガ3脂肪酸と;
b.ウリジン、デオキシウリジン、ウリジンリン酸、ウラシル、アシル化ウリジン、及びシチジンから選択されるウリジン源と;
を含む、対象の認知を改善するため、及び/又は認知機能障害の治療又は予防に使用するための組成物に関する。
100〜500mg、好ましくは200〜400mgのEPA、
1000〜1500mg、好ましくは1100〜1300mgのDHA、
50〜600mg、好ましくは60〜200mgのリン脂質、
200〜600mg、好ましくは300〜500mgのコリン、
400〜800mg、好ましくは500〜700mgのUMP(ウリジン一リン酸)、
20〜60mg、好ましくは30〜50mgのビタミンE(アルファTE)、
60〜100mg、好ましくは70〜90mgのビタミンC、
40〜80μg、好ましくは50〜70μgのセレン、
1〜5μg、好ましくは2〜4μgのビタミンB12、
0.5〜3mg、好ましくは0.5〜2mgのビタミンB6、及び
200〜600μg、好ましくは300〜500μgの葉酸
を含む。
a.ドコサヘキサエン酸(DHA)、エイコサペンタエン酸(EPA)、及びドコサペンタエン酸(DPA)からなる群より選択される1つ以上のオメガ3脂肪酸と;
b.ウリジン、デオキシウリジン、ウリジンリン酸、ウラシル、アシル化ウリジン、及びシチジンから選択されるウリジン源と
を含む組成物を投与することを含む方法にも関する。
− (a)ドコサヘキサエン酸(DHA)、エイコサペンタエン酸(EPA)、及びドコサペンタエン酸(DPA)からなる群より選択される1つ以上のオメガ3脂肪酸と;(b)ウリジン、デオキシウリジン、ウリジンリン酸、ウラシル、及びアシル化ウリジンから選択されるウリジン源とを含む組成物を投与することと、
− 以下の神経学的検査:
− RAVLT認知検査、
− RBANS認知検査、及び
− CVLT認知検査
のうちの1つ以上の検査により対象をモニタリング又は評価することと
を含む。
a.ドコサヘキサエン酸(DHA)、及び/又はエイコサペンタエン酸(EPA)、及び/又はドコサペンタエン酸(DPA)と;
b.ウリジン、デオキシウリジン、ウリジンリン酸、ウラシル、アシル化ウリジン、及びシチジンから選択されるウリジン源と
を含む、対象の認知の改善、及び/又は認知機能障害の治療又は予防に使用するための組成物に関する。
好ましくは、本発明において、対象は薬剤未投与の対象である。特に、対象は、本発明による組成物を投与する前に、記憶の改善のため及び/又はアルツハイマー病のためのいかなる薬剤も投与されていない。
− 脳脊髄液(CSF)1リットル当たりの総タウのレベルが350ngを超える;
− CSF中のアミロイドベータ42/リン酸化タウ181の重量比が6.5未満である;
− 内側側頭葉(MTL)萎縮症が存在し、目視採点を用いた定性的評価(標準年齢のはっきり特徴づけられる集団を基準とした)又は対象の領域の定量的な体積測定(標準年齢のはっきり特徴づけられる集団を基準とした)のいずれかにより磁気共鳴画像(MRI)において証明される、海馬、嗅内皮質、又は扁桃体の体積減少があること
− 定性的評価又は定量的な体積測定によりMRIにおいて証明される、前頭側頭葉(FTL)萎縮症が存在すること;
− CSF 1mL当たりのF2イソプロスタン(F2−IsoP、イソプロスタン8,12−イソ−iPF2アルファ−VI)のレベルが25pgを超える。
− 陽電子放射断層撮影(PET)により検出できる、脳の両側側頭頭頂領域でのグルコース代謝の低下;
− PETにより検出できる、後帯状皮質でのグルコース代謝の低下;
− 例えば放射性同位体99mTc−HMPAOを適用することにより、単一光子放射型コンピュータ断層撮影法(SPECT)を適用することにより測定できる、脳の血流の低下);
− SPECTを適用することにより測定できる、脳でのグルコース代謝の低下;
− MRIにより測定できる内側側頭葉若しくは下側頭葉の組織像の異常、又はグルコース利用率の異常;
− 側頭頭頂葉皮質又は後帯状皮質での、組織像又はグルコース利用の異常。
アルツハイマー病患者、特に薬剤未投与のアルツハイマー病患者において、認知機能の改善が特に見出された。
神経心理学的検査は、例えば実施例の項で説明されるような臨床検査において、特定の脳の構造又は経路と関連していることが知られている心理学的機能を測定するのに使用される、特別に考案された課題である。検査は、脳の機能の研究のため、また臨床状況では障害の診断のために使用される。それらは通常、公式な環境での明確に規定される手順の系統的な実施を含み、個人的、対人的、及び文脈的要素を伴って神経心理学的評価を行うプロセスの中心的な構成部分を形成する(出典:http://en.wikipedia.org/wiki/Neuropsychological_test)。
対連合学習検査は、対象が記憶の中で2つのものを結び付けることを要求する。このパラダイムを特色とするいくつかの課題は、対象が色を形と結び付ける、又は物体を空間的位置と結び付けることを要求する。
好ましくは、本発明に従って投与しようとする組成物は、ウリジン、デオキシウリジン、ウリジンリン酸、ウラシル、アシル化ウリジン、及びシチジンから選択されるウリジン源とを含む。
本発明の組成物は、好ましくは飽和及び/又はモノ不飽和脂肪酸を含む。飽和脂肪酸の量は、好ましくは全脂肪酸に対して6〜60重量%、好ましくは12〜40重量%、より好ましくは全脂肪酸に対して20〜40重量%である。特に、C14:0(ミリスチン酸)+C16:0(パルミチン酸)の量は、全脂肪酸に対して好ましくは5〜50重量%、好ましくは8〜36重量%、より好ましくは15〜30重量%である。オレイン酸及びパルミトオレイン酸などのモノ不飽和脂肪酸の総量は、好ましくは5〜40重量%、より好ましくは15〜30重量%である。これらの好ましい量を含む組成物は非常に有効であることが見出された。
好ましくは、本発明の組成物は、好ましくはリン脂質を含み、好ましくは脂質の全重量に対して0.1〜50重量%のリン脂質、より好ましくは0.5〜20重量%、より好ましくは1〜10%重量%、最も好ましくは脂質の全重量に対して1〜5重量%のリン脂質を含む。脂質の総量は、好ましくは乾燥物質については10〜30重量%であり、及び/又は液体組成物については100ml当たりの脂質が2〜10gである。組成物は、好ましくは100ml当たり0.01〜1グラムのレシチン、より好ましくは100ml当たり0.05〜0.5グラムのレシチンを含む。これらの好ましい量を含む組成物は非常に有効であることが見出された。
好ましくは、本発明の組成物はコリン及び/又はホスファチジルコリンを含有する。本発明の方法は、好ましくは1日当たり50mgを超えるコリン、好ましくは1日当たり80〜2000mgのコリン、より好ましくは1日当たり120〜1000mgのコリン、最も好ましくは1日当たり150〜600mgのコリンを投与することを含む。本発明の組成物は、好ましくは液体配合物100ml当たり50mg〜3グラムのコリン、好ましくは100ml当たり200mg〜1000mgのコリンを含む。
組成物は有利にはビタミンを含有していてもよく、好ましくはビタミンC、ビタミンE、及びビタミンB、より好ましくはビタミンC、ビタミンE、ビタミンB6、ビタミンB12、及び葉酸を含有していてもよい。有利には、ビタミンB12及び葉酸塩が含まれる。本発明の組成物は、好ましくは液体製品100ml当たり50〜1000μgの葉酸、より好ましくは150〜750μg、最も好ましくは200〜500μgの葉酸を含む。本発明の方法は、好ましくは1日当たり50〜1000μgの葉酸、より好ましくは150〜750μg、最も好ましくは1日当たり200〜500μgの葉酸を投与することを含む。本発明の組成物は、好ましくは液体製品100ml当たり0.5〜15μgのビタミンB12、より好ましくは1〜10μg、最も好ましくは1.5〜5μgのビタミンB12を含む。本発明の方法は、好ましくは1日当たり0.5〜15μgのビタミンB12、より好ましくは1〜10μg、最も好ましくは1日当たり1.5〜5μgのビタミンB12を投与することを含む。
好ましくは、本発明による組成物は、
− ドコサヘキサエン酸(DHA)、エイコサペンタエン酸(EPA)、及びドコサペンタエン酸(DPA)からなる群より選択される1つ以上のオメガ3脂肪酸と;
− ウリジン、デオキシウリジン、ウリジンリン酸、ウラシル、アシル化ウリジン、及びシチジンから選択されるウリジン源と
を含む。
− 100〜500mg、好ましくは200〜400mgのEPA、
− 900〜1500mg、好ましくは950〜1300mgのDHA、
− 50〜600mg、好ましくは60〜200mgのリン脂質、
− 200〜600mg、好ましくは300〜500mgのコリン、
− 400〜800mg、好ましくは500〜700mgのUMP(ウリジン一リン酸)、
− 20〜60mg、好ましくは30〜50mgのビタミンE(アルファ−TE)、
− 60〜100mg、好ましくは60〜90mgのビタミンC、
− 40〜80μg、好ましくは45〜65μgのセレン、
− 1〜5μg、好ましくは2〜4μgのビタミンB12、
− 0.5〜3mg、好ましくは0.5〜2mgのビタミンB6、及び
− 200〜600μg、好ましくは300〜500μg葉酸
を含む。
− 100〜500mg、好ましくは200〜400mgのEPA、
− 900〜1500mg、好ましくは950〜1300mgのDHA、
− 50〜600mg、好ましくは60〜200mgのリン脂質、
− 200〜600mg、好ましくは300〜500mgのコリン、
− 400〜800mg、好ましくは500〜700mgのUMP(ウリジン一リン酸)、
− 20〜60mg、好ましくは30〜50mgのビタミンE(アルファTE)、
− 60〜100mg、好ましくは60〜90mgのビタミンC、
− 40〜80μg、好ましくは45〜65μgのセレン、
− 1〜5μg、好ましくは2〜4μgのビタミンB12、
− 0.5〜3mg、好ましくは0.5〜2mgのビタミンB6、及び
− 200〜600μg、好ましくは300〜500μgの葉酸
を含む。
125ml当たり、以下を含む包装された組成物:
エネルギー 125kcal;タンパク質 3.9g;炭水化物 16.5g;脂肪 4.9g。
臨床研究。
本発明の研究は無作為比較二重盲検試験であり、欧州の6カ国(オランダ、ドイツ、フランス、ベルギー、イタリア、及びスペイン)の27の研究センターで行われた。軽度のAD(MMSE点数≧20)、及びNINCDS−ADRDA基準に従いADと推定される診断を有する、薬剤未投与の患者を、実施例1の組成物、又は等カロリーの対照製品に、ランダムに割り当てた(1:1)。介在期間は24週間であった。
全部で259人の薬剤未投与の対象を無作為抽出した(スクリーニング不適格2.6%)。調査対象母集団の全体において、調査グループ間でベースライン特性の違いは見られなかった。平均年齢は73.8(±7.7)歳、平均スクリーニングMMSEは25.0(±2.8)であり、51%が男性であった。計算される標本サイズが十分であるかどうか、また安全性の懸念が生じていないことをチェックするために、あらかじめ定められた盲検での中間解析を行い、独立データモニタリング委員会は修正を行わずに試験を継続することを勧告した。無作為抽出の259人の対象のうち、238人の対象(91.9%)が調査を完了した。5人の対象は(重篤)有害事象((S)AE)のために調査を完了しなかった;3人は組成物を摂取したグループであり、2人は対照のグループであり、(S)AEの発生において調査グループ間の違いは見られなかった。血液の安全性パラメーターにおいて、臨床的に関連する違いは見られなかった。24週間の平均コンプライアンスは97%で非常に高く、グループ間で違いは無かった。高いコンプライアンスは、コンプライアンスの(栄養的な)バイオマーカー、例えば赤血球膜中のドコサヘキサエン酸及び血漿ホモシステインの著しい重大な変化によって裏付けられた。
Claims (25)
- a.ドコサヘキサエン酸(DHA)、エイコサペンタエン酸(EPA)、及びドコサペンタエン酸(DPA)からなる群より選択される1つ以上のオメガ3脂肪酸と;
b.ウリジン、デオキシウリジン、ウリジンリン酸、ウラシル、アシル化ウリジン、及びシチジンから選択されるウリジン源と;
を含む、対象の認知を改善するため、及び/又は対象の認知機能障害の治療又は予防に使用するための組成物であって、
ここで、前記対象の認知を、以下の神経学的検査:RAVLT認知検査、RBANS認知検査、及びCVLT認知検査のうちの1つ以上の検査により評価する、組成物。 - 前記対象が、アルツハイマー病、軽度の認知機能障害、加齢に伴う記憶障害、多発性硬化症、血管性認知症、前頭側頭型認知症、意味性認知症、又はレビー小体型認知症のうちの1つ以上の症状を有する、請求項1に記載の組成物。
- 前記対象が、前駆期認知症及び/又は前駆期アルツハイマー患者である、請求項1又は2に記載の組成物。
- 前記組成物が、1日用量当たり又は組成物100ml当たり、少なくとも500mgのDHA及び少なくとも50mgのウリジンを含む、請求項1〜3のいずれか一項に記載の組成物。
- 前記組成物が、1日用量当たり又は組成物100ml当たり、少なくとも600mgのDHAを含む、請求項4に記載の組成物。
- 前記組成物が、1日用量当たり又は組成物100ml当たり、少なくとも100mgのウリジンを含む、請求項4又は5に記載の組成物。
- 前記組成物が、コリン、又はその塩、若しくはそのエステルをさらに含む、請求項1〜6のいずれか一項に記載の組成物。
- 前記組成物が、1日用量当たり又は組成物100ml当たり、200〜600mgのコリンを含む、請求項7に記載の組成物。
- 前記組成物が、1日用量当たり又は組成物100ml当たり、300〜400mgのコリンを含む、請求項8に記載の組成物。
- 前記組成物が、リン脂質、ビタミンE、ビタミンC、セレン、ビタミンB12、ビタミンB6、及び葉酸からなる群より選択される構成成分/成分のうちの1つ以上をさらに含む、請求項1〜9のいずれか一項に記載の組成物。
- 前記組成物が、1日用量当たり又は組成物100ml当たり、
− 50〜1000mgのリン脂質、
− 0.5〜3mgのビタミンB6、
− 50〜500μgの葉酸、
− 1〜30μgのビタミンB12
を含む、請求項10に記載の組成物。 - 前記組成物が、1日用量当たり又は組成物100ml当たり、20〜60mgのビタミンE、及び60〜100mgのビタミンCを含む、請求項10又は11に記載の組成物。
- 前記組成物が、アルファトコフェロールの形態のビタミンEを含む、請求項12に記載の組成物。
- 前記組成物が、1日用量当たり又は組成物100ml当たり、
− 100〜500mgのEPA、
− 1000〜1500mgのDHA、
− 50〜600mgのリン脂質、
− 200〜600mgのコリン、
− 400〜800mgのウリジン一リン酸、
− 20〜60mgのビタミンE、
− 60〜100mgのビタミンC、
− 40〜80μgのセレン、
− 1〜5μgのビタミンB12、
− 0.5〜3mgのビタミンB6、及び
− 200〜600μgの葉酸
を含む、請求項10〜13のいずれか一項に記載の組成物。 - 前記組成物が、1日用量当たり又は組成物100ml当たり、
− 200〜400mgのEPA、
− 1100〜1300mgのDHA、
− 60〜200mgのリン脂質、
− 300〜500mgのコリン、
− 500〜700mgのウリジン一リン酸、
− 30〜50mgのビタミンE、
− 70〜90mgのビタミンC、
− 50〜70μgのセレン、
− 2〜4μgのビタミンB12、
− 0.5〜2mgのビタミンB6、及び
− 300〜500μgの葉酸
を含む、請求項14に記載の組成物。 - 前記組成物が、アルファトコフェロールの形態のビタミンEを含む、請求項14又は15に記載の組成物。
- 前記組成物は、1日用量当たり又は組成物100ml当たり、エネルギー含量が50〜130kcal、タンパク質含量が1〜10g、脂質の脂質含量が1〜5g、可消化炭水化物の含量が4〜20gである、請求項1〜16のいずれか一項に記載の組成物。
- 前記対象は、ミニメンタルステート検査(MMSE)のスコアが20〜30である、請求項1〜17のいずれか一項に記載の組成物。
- 前記対象は、ミニメンタルステート検査(MMSE)のスコアが20〜26である、請求項18に記載の組成物。
- 前記対象は、ミニメンタルステート検査(MMSE)のスコアが24〜26である、請求項19に記載の組成物。
- 前記対象が薬剤未投与である、請求項1〜20のいずれか一項に記載の組成物。
- 前記組成物が、少なくとも12週の期間にわたって、1日に少なくとも1回、患者に経腸投与される、請求項1〜21のいずれか一項に記載の組成物。
- 前記組成物が、少なくとも13週の期間にわたって、1日に少なくとも1回、患者に経腸投与される、請求項22に記載の組成物。
- 前記組成物が、少なくとも14、15、16、17、18、19、20、21、22、23、又は24週の期間にわたって、1日に少なくとも1回、患者に経腸投与される、請求項23に記載の組成物。
- 対象の認知を改善するため、及び/又は対象の認知機能障害の治療又は予防に使用するための製品の製造のための組成物の使用であって、
ここで、前記対象の認知を、以下の神経学的検査:RAVLT認知検査、RBANS認知検査、及びCVLT認知検査のうちの1つ以上の検査により評価する請求項1、4〜17のいずれか一項に記載の組成物の使用。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
NLPCT/NL2011/050737 | 2011-10-31 | ||
PCT/NL2011/050737 WO2013066151A1 (en) | 2011-10-31 | 2011-10-31 | Improving recognition |
PCT/NL2012/050751 WO2013066165A1 (en) | 2011-10-31 | 2012-10-30 | Improving recognition |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2014534225A JP2014534225A (ja) | 2014-12-18 |
JP6272766B2 true JP6272766B2 (ja) | 2018-01-31 |
Family
ID=47144032
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2014539897A Expired - Fee Related JP6272766B2 (ja) | 2011-10-31 | 2012-10-30 | 認知の改善 |
Country Status (13)
Country | Link |
---|---|
US (1) | US9763971B2 (ja) |
EP (1) | EP2773338B1 (ja) |
JP (1) | JP6272766B2 (ja) |
CN (1) | CN104039318B (ja) |
AU (1) | AU2012331689B2 (ja) |
BR (1) | BR112014010162A8 (ja) |
CA (1) | CA2853971C (ja) |
ES (1) | ES2720660T3 (ja) |
HK (1) | HK1201742A1 (ja) |
PL (1) | PL2773338T3 (ja) |
PT (1) | PT2773338T (ja) |
RU (1) | RU2638809C2 (ja) |
WO (2) | WO2013066151A1 (ja) |
Families Citing this family (19)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2013066152A1 (en) * | 2011-10-31 | 2013-05-10 | N.V. Nutricia | Method for improving executive function |
BR112014020177A8 (pt) * | 2012-03-02 | 2021-10-19 | Nutricia Nv | Uso de uma composição para a fabricação de um produto para diminuir, prevenir ou reverter a conectividade cerebral funcional prejudicada e/ou organização da rede cerebral prejudicada |
WO2015115886A1 (en) * | 2014-01-31 | 2015-08-06 | N.V. Nutricia | Method for treating, stabilizing or slowing down brain glucose metabolism deficit |
WO2015115885A1 (en) | 2014-01-31 | 2015-08-06 | N.V. Nutricia | Method for reducing white matter lesions, white matter hyperintensities (wmh), leukoaraiosis or periventricular white matter disease in elderly |
WO2016148561A1 (en) * | 2015-03-16 | 2016-09-22 | N.V. Nutricia | Method for improving bladder function |
WO2017069613A1 (en) * | 2015-10-23 | 2017-04-27 | N.V. Nutricia | Method for improving recognition and/or working memory in hyperphenylalanimenia and phenylketonuria patients |
US11000496B2 (en) | 2015-12-04 | 2021-05-11 | Societe Des Produits Nestle S.A. | Medium chain triglyceride compositions |
AU2017224301B2 (en) * | 2016-02-22 | 2021-01-21 | Newtricious B.V. | Composition for the prevention or treatment of neurodegenerative diseases. |
WO2017155386A1 (en) * | 2016-03-08 | 2017-09-14 | N.V. Nutricia | Method for treating brain atrophy |
WO2017179644A1 (ja) * | 2016-04-15 | 2017-10-19 | 慶裕 広川 | 認知機能改善剤 |
WO2017213490A1 (en) | 2016-06-10 | 2017-12-14 | N.V. Nutricia | Method for controlling neuroinflammation |
CN108079008A (zh) | 2016-11-23 | 2018-05-29 | 上海泽生科技开发股份有限公司 | 促进胃肠系统动力的复合维生素组合物 |
CN108567792A (zh) * | 2017-03-07 | 2018-09-25 | 上海泽生科技开发股份有限公司 | 一种治疗阿尔茨海默病的复合维生素组合物 |
CN107889992A (zh) * | 2017-11-18 | 2018-04-10 | 杨越安 | 一种预防和治疗痴呆的功能保健饮料 |
CN108922292A (zh) * | 2018-07-27 | 2018-11-30 | 李明旭 | 用于延缓老年人认知能力衰退的训练方法及训练系统 |
JP7101087B2 (ja) * | 2018-09-05 | 2022-07-14 | 株式会社 伊藤園 | 軽度認知障害に対する緑茶成分の有効性評価方法 |
IT201900013707A1 (it) * | 2019-08-01 | 2021-02-01 | Cristalfarma S R L | Integratore alimentare, per uso come coadiuvante, per la prevenzione della demenza vascolare |
JPWO2022244727A1 (ja) * | 2021-05-17 | 2022-11-24 | ||
EP4401580A1 (en) | 2021-09-17 | 2024-07-24 | N.V. Nutricia | Solid composition suitable as a nutritional composition or supplement for animals that suffer from brain related disorders, decline or diseases |
Family Cites Families (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5470838A (en) | 1987-10-28 | 1995-11-28 | Pro-Neuron, Inc. | Method of delivering exogenous uridine or cytidine using acylated uridine or cytidine |
US8518882B2 (en) | 1998-07-31 | 2013-08-27 | Massachusetts Institute Of Technology | Methods and compositions for ameliorating or inhibiting decline in memory or intelligence or improving same |
RU2429851C2 (ru) * | 2005-05-23 | 2011-09-27 | Массачусетс Инститьют Оф Текнолоджи | Композиции, содержащие pufa и/или уридин, и способы их применения |
ES2366034T3 (es) * | 2005-12-23 | 2011-10-14 | N.V. Nutricia | Composición que comprende ácidos grasos poliinsaturados, proteínas, manganeso y/o molibdeno y nucleósidos/nucleótidos para el tratamiento de la demencia. |
DK2170316T3 (en) * | 2007-06-26 | 2014-02-24 | Nutricia Nv | Improvement of memory in people with mini mental status test at 24-26 |
WO2009002145A1 (en) | 2007-06-26 | 2008-12-31 | N.V. Nutricia | Lipid composition for improving function of brain functioning |
WO2009002148A1 (en) * | 2007-06-27 | 2008-12-31 | N.V. Nutricia | Food composition for prodromal dementia patients |
WO2009002146A1 (en) | 2007-06-26 | 2008-12-31 | N.V. Nutricia | Supporting activities of daily living |
WO2009057994A1 (en) | 2007-11-02 | 2009-05-07 | N.V. Nutricia | Unit dosage for brain health |
PL2609812T3 (pl) * | 2007-12-20 | 2019-02-28 | N.V. Nutricia | Ciekły produkt zawierający nukleotydy/nukleozydy |
US8282335B2 (en) | 2009-06-12 | 2012-10-09 | Rs Drawings, Llc | Liftgate and mounting bracket system |
SG10201500620PA (en) | 2009-07-24 | 2015-03-30 | Amazentis Sa | Compounds, compositions and methods for protecting brain health in neurodegenerative disorders |
WO2017069613A1 (en) | 2015-10-23 | 2017-04-27 | N.V. Nutricia | Method for improving recognition and/or working memory in hyperphenylalanimenia and phenylketonuria patients |
-
2011
- 2011-10-31 WO PCT/NL2011/050737 patent/WO2013066151A1/en active Application Filing
-
2012
- 2012-10-30 CN CN201280065552.XA patent/CN104039318B/zh active Active
- 2012-10-30 RU RU2014121891A patent/RU2638809C2/ru not_active IP Right Cessation
- 2012-10-30 EP EP12783360.6A patent/EP2773338B1/en not_active Revoked
- 2012-10-30 PL PL12783360T patent/PL2773338T3/pl unknown
- 2012-10-30 AU AU2012331689A patent/AU2012331689B2/en not_active Ceased
- 2012-10-30 BR BR112014010162A patent/BR112014010162A8/pt not_active IP Right Cessation
- 2012-10-30 PT PT12783360T patent/PT2773338T/pt unknown
- 2012-10-30 WO PCT/NL2012/050751 patent/WO2013066165A1/en active Application Filing
- 2012-10-30 JP JP2014539897A patent/JP6272766B2/ja not_active Expired - Fee Related
- 2012-10-30 CA CA2853971A patent/CA2853971C/en not_active Expired - Fee Related
- 2012-10-30 US US14/355,197 patent/US9763971B2/en active Active
- 2012-10-30 ES ES12783360T patent/ES2720660T3/es active Active
-
2015
- 2015-03-09 HK HK15102334.4A patent/HK1201742A1/xx not_active IP Right Cessation
Also Published As
Publication number | Publication date |
---|---|
JP2014534225A (ja) | 2014-12-18 |
CN104039318A (zh) | 2014-09-10 |
CA2853971C (en) | 2020-03-10 |
BR112014010162A2 (pt) | 2017-06-13 |
EP2773338B1 (en) | 2019-02-06 |
RU2014121891A (ru) | 2015-12-10 |
AU2012331689B2 (en) | 2017-03-30 |
PT2773338T (pt) | 2019-04-30 |
CA2853971A1 (en) | 2013-05-10 |
US20140274938A1 (en) | 2014-09-18 |
HK1201742A1 (en) | 2015-09-11 |
AU2012331689A1 (en) | 2014-06-05 |
US9763971B2 (en) | 2017-09-19 |
RU2638809C2 (ru) | 2017-12-15 |
EP2773338A1 (en) | 2014-09-10 |
WO2013066151A1 (en) | 2013-05-10 |
PL2773338T3 (pl) | 2019-08-30 |
CN104039318B (zh) | 2018-05-11 |
WO2013066165A1 (en) | 2013-05-10 |
ES2720660T3 (es) | 2019-07-23 |
BR112014010162A8 (pt) | 2017-06-20 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6272766B2 (ja) | 認知の改善 | |
JP5934265B2 (ja) | ミニメンタルステート検査24〜26点の被験者における記憶力改善 | |
RU2667968C2 (ru) | Способ улучшения функциональной синаптической связи | |
US8445458B2 (en) | Food composition for prodromal dementia patients | |
JP6444735B2 (ja) | 実行機能を向上させるための方法 | |
Kiso | Pharmacology in health foods: effects of arachidonic acid and docosahexaenoic acid on the age-related decline in brain and cardiovascular system function | |
WO2013129914A1 (en) | Method for improving functional synaptic connectivity | |
JP6719860B2 (ja) | 神経心理学的検査バッテリースコアを向上させるための組成物 | |
WO2016072842A1 (en) | Method for preventing, reducing the risk of, or treating behavioral frontotemporal dementia | |
WO2015115898A1 (en) | Method for treating, stabilizing or slowing down brain glucose metabolism deficit | |
WO2013066153A1 (en) | Composition for improving neuropsychological test battery score |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20151002 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20160705 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20161005 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20161205 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20170207 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20170607 |
|
A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20170614 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20170822 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20171116 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20171205 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20180104 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6272766 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
LAPS | Cancellation because of no payment of annual fees |