US20100331258A1 - memory in subjects with mini-mental state examination of 24-26 - Google Patents
memory in subjects with mini-mental state examination of 24-26 Download PDFInfo
- Publication number
- US20100331258A1 US20100331258A1 US12/666,611 US66661108A US2010331258A1 US 20100331258 A1 US20100331258 A1 US 20100331258A1 US 66661108 A US66661108 A US 66661108A US 2010331258 A1 US2010331258 A1 US 2010331258A1
- Authority
- US
- United States
- Prior art keywords
- composition
- uridine
- subject
- vitamin
- per
- 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.)
- Abandoned
Links
- 230000015654 memory Effects 0.000 title claims abstract description 11
- 239000000203 mixture Substances 0.000 claims abstract description 70
- 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 abstract description 32
- 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 abstract description 29
- 235000020669 docosahexaenoic acid Nutrition 0.000 claims abstract description 24
- 235000020673 eicosapentaenoic acid Nutrition 0.000 claims abstract description 21
- 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 abstract description 20
- 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 abstract description 20
- 238000011282 treatment Methods 0.000 claims abstract description 16
- 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 abstract description 15
- DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 claims abstract description 15
- 229940045145 uridine Drugs 0.000 claims abstract description 15
- 230000006386 memory function Effects 0.000 claims abstract description 14
- 230000001771 impaired effect Effects 0.000 claims abstract description 9
- 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 abstract description 8
- 229940090949 docosahexaenoic acid Drugs 0.000 claims abstract description 8
- 229960005135 eicosapentaenoic acid Drugs 0.000 claims abstract description 8
- JAZBEHYOTPTENJ-UHFFFAOYSA-N eicosapentaenoic acid Natural products CCC=CCC=CCC=CCC=CCC=CCCCC(O)=O JAZBEHYOTPTENJ-UHFFFAOYSA-N 0.000 claims abstract description 8
- 230000002265 prevention Effects 0.000 claims abstract description 7
- 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 19
- 238000000034 method Methods 0.000 claims description 17
- 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 14
- 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 14
- 230000003111 delayed effect Effects 0.000 claims description 14
- 229960001231 choline Drugs 0.000 claims description 13
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 claims description 13
- 230000006870 function Effects 0.000 claims description 12
- 229930003779 Vitamin B12 Natural products 0.000 claims description 10
- 235000019152 folic acid Nutrition 0.000 claims description 10
- 239000011724 folic acid Substances 0.000 claims description 10
- 235000018102 proteins Nutrition 0.000 claims description 10
- 102000004169 proteins and genes Human genes 0.000 claims description 10
- 108090000623 proteins and genes Proteins 0.000 claims description 10
- LXNHXLLTXMVWPM-UHFFFAOYSA-N pyridoxine Chemical compound CC1=NC=C(CO)C(CO)=C1O LXNHXLLTXMVWPM-UHFFFAOYSA-N 0.000 claims description 10
- 235000019163 vitamin B12 Nutrition 0.000 claims description 10
- 239000011715 vitamin B12 Substances 0.000 claims description 10
- 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 9
- 229960000304 folic acid Drugs 0.000 claims description 9
- 229940067631 phospholipid Drugs 0.000 claims description 9
- 150000003904 phospholipids Chemical class 0.000 claims description 9
- 239000012263 liquid product Substances 0.000 claims description 8
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 claims description 7
- 229930003268 Vitamin C Natural products 0.000 claims description 7
- 229930003427 Vitamin E Natural products 0.000 claims description 7
- 235000014633 carbohydrates Nutrition 0.000 claims description 7
- 150000001720 carbohydrates Chemical class 0.000 claims description 7
- 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 7
- 239000011718 vitamin C Substances 0.000 claims description 7
- 235000019154 vitamin C Nutrition 0.000 claims description 7
- 239000011709 vitamin E Substances 0.000 claims description 7
- 235000019165 vitamin E Nutrition 0.000 claims description 7
- 229940046009 vitamin E Drugs 0.000 claims description 7
- BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical compound [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 claims description 5
- RADKZDMFGJYCBB-UHFFFAOYSA-N pyridoxal hydrochloride Natural products CC1=NC=C(CO)C(C=O)=C1O RADKZDMFGJYCBB-UHFFFAOYSA-N 0.000 claims description 5
- 235000011649 selenium Nutrition 0.000 claims description 5
- 239000011669 selenium Substances 0.000 claims description 5
- 229910052711 selenium Inorganic materials 0.000 claims description 5
- 235000019158 vitamin B6 Nutrition 0.000 claims description 5
- 239000011726 vitamin B6 Substances 0.000 claims description 5
- 229940011671 vitamin b6 Drugs 0.000 claims description 5
- FDJOLVPMNUYSCM-WZHZPDAFSA-L cobalt(3+);[(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+3].N#[C-].N([C@@H]([C@]1(C)[N-]\C([C@H]([C@@]1(CC(N)=O)C)CCC(N)=O)=C(\C)/C1=N/C([C@H]([C@@]1(CC(N)=O)C)CCC(N)=O)=C\C1=N\C([C@H](C1(C)C)CCC(N)=O)=C/1C)[C@@H]2CC(N)=O)=C\1[C@]2(C)CCC(=O)NC[C@@H](C)OP([O-])(=O)O[C@H]1[C@@H](O)[C@@H](N2C3=CC(C)=C(C)C=C3N=C2)O[C@@H]1CO FDJOLVPMNUYSCM-WZHZPDAFSA-L 0.000 claims 1
- 206010012289 Dementia Diseases 0.000 abstract description 12
- 238000012360 testing method Methods 0.000 abstract description 7
- 206010027175 memory impairment Diseases 0.000 abstract description 5
- 230000009745 pathological pathway Effects 0.000 abstract description 5
- 230000002441 reversible effect Effects 0.000 abstract description 2
- 239000000047 product Substances 0.000 description 14
- 235000014113 dietary fatty acids Nutrition 0.000 description 11
- 229940079593 drug Drugs 0.000 description 11
- 229930195729 fatty acid Natural products 0.000 description 11
- 239000000194 fatty acid Substances 0.000 description 11
- 150000004665 fatty acids Chemical class 0.000 description 11
- 208000024827 Alzheimer disease Diseases 0.000 description 9
- 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 description 9
- 239000003814 drug Substances 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
- 230000000694 effects Effects 0.000 description 8
- 230000006993 memory improvement Effects 0.000 description 7
- 239000007788 liquid Substances 0.000 description 6
- 150000002632 lipids Chemical class 0.000 description 5
- -1 uridine phosphates Chemical class 0.000 description 5
- 235000021342 arachidonic acid Nutrition 0.000 description 4
- 229940114079 arachidonic acid Drugs 0.000 description 4
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 4
- 230000006872 improvement Effects 0.000 description 4
- 235000020660 omega-3 fatty acid Nutrition 0.000 description 4
- 230000007497 verbal memory 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
- 235000021281 monounsaturated fatty acids Nutrition 0.000 description 3
- 238000011903 nutritional therapy Methods 0.000 description 3
- 235000003441 saturated fatty acids Nutrition 0.000 description 3
- 239000010902 straw Substances 0.000 description 3
- TUNFSRHWOTWDNC-UHFFFAOYSA-N tetradecanoic acid Chemical compound CCCCCCCCCCCCCC(O)=O TUNFSRHWOTWDNC-UHFFFAOYSA-N 0.000 description 3
- JZRWCGZRTZMZEH-UHFFFAOYSA-N thiamine Chemical compound CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N JZRWCGZRTZMZEH-UHFFFAOYSA-N 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
- 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
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerol Natural products OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-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
- 229910019142 PO4 Inorganic materials 0.000 description 2
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical class O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-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
- 230000008901 benefit Effects 0.000 description 2
- 230000019771 cognition Effects 0.000 description 2
- 230000007423 decrease Effects 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
- 229940067606 lecithin Drugs 0.000 description 2
- 239000000787 lecithin Substances 0.000 description 2
- 235000010445 lecithin Nutrition 0.000 description 2
- 235000016709 nutrition Nutrition 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- 229940012843 omega-3 fatty acid Drugs 0.000 description 2
- 239000006014 omega-3 oil Substances 0.000 description 2
- 235000020665 omega-6 fatty acid Nutrition 0.000 description 2
- 229940033080 omega-6 fatty acid Drugs 0.000 description 2
- SECPZKHBENQXJG-FPLPWBNLSA-N palmitoleic acid Chemical compound CCCCCC\C=C/CCCCCCCC(O)=O SECPZKHBENQXJG-FPLPWBNLSA-N 0.000 description 2
- 235000021317 phosphate Nutrition 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 208000024891 symptom Diseases 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
- MXHRCPNRJAMMIM-SHYZEUOFSA-N 2'-deoxyuridine Chemical class C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 MXHRCPNRJAMMIM-SHYZEUOFSA-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
- 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
- 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
- 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
- 241000195493 Cryptophyta Species 0.000 description 1
- SBJKKFFYIZUCET-JLAZNSOCSA-N Dehydro-L-ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(=O)C1=O SBJKKFFYIZUCET-JLAZNSOCSA-N 0.000 description 1
- 235000008100 Ginkgo biloba Nutrition 0.000 description 1
- 244000194101 Ginkgo biloba Species 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
- 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
- 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
- 235000021314 Palmitic acid Nutrition 0.000 description 1
- 235000021319 Palmitoleic acid Nutrition 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 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
- 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
- 230000032683 aging Effects 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- OGBUMNBNEWYMNJ-UHFFFAOYSA-N batilol Chemical class CCCCCCCCCCCCCCCCCCOCC(O)CO OGBUMNBNEWYMNJ-UHFFFAOYSA-N 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
- 230000037396 body weight 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
- 230000008859 change 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
- SECPZKHBENQXJG-UHFFFAOYSA-N cis-palmitoleic acid Natural products CCCCCCC=CCCCCCCCC(O)=O SECPZKHBENQXJG-UHFFFAOYSA-N 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- MXHRCPNRJAMMIM-UHFFFAOYSA-N desoxyuridine Chemical class C1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 MXHRCPNRJAMMIM-UHFFFAOYSA-N 0.000 description 1
- 235000005686 eating Nutrition 0.000 description 1
- 235000013601 eggs Nutrition 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 229940014144 folate Drugs 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 235000021588 free fatty acids Nutrition 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-OUBTZVSYSA-N magnesium-25 atom Chemical compound [25Mg] FYYHWMGAXLPEAU-OUBTZVSYSA-N 0.000 description 1
- 229910052748 manganese Inorganic materials 0.000 description 1
- 239000011572 manganese Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000018984 mastication Effects 0.000 description 1
- 238000010077 mastication Methods 0.000 description 1
- 238000005259 measurement Methods 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
- 235000020124 milk-based beverage Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 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
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 235000015097 nutrients 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
- 229940055726 pantothenic acid Drugs 0.000 description 1
- 235000019161 pantothenic acid Nutrition 0.000 description 1
- 239000011713 pantothenic acid Substances 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
- 239000011574 phosphorus Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 150000004671 saturated fatty acids Chemical class 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000008347 soybean phospholipid Substances 0.000 description 1
- 230000009747 swallowing Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 235000019157 thiamine Nutrition 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
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- 125000005457 triglyceride group Chemical group 0.000 description 1
- 229940035893 uracil Drugs 0.000 description 1
- 235000019156 vitamin B Nutrition 0.000 description 1
- 239000011720 vitamin B Substances 0.000 description 1
- 229940082632 vitamin b12 and folic acid Drugs 0.000 description 1
- 229940033158 vitamin b6 1 mg Drugs 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- 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
- 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
-
- 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
-
- 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
- A23L33/15—Vitamins
-
- 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
- A23L33/16—Inorganic salts, minerals or trace elements
-
- 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
- A23L33/40—Complete food formulations for specific consumer groups or specific purposes, e.g. infant formula
-
- 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
- A61K31/33—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
- A61K31/557—Eicosanoids, e.g. leukotrienes or prostaglandins
-
- 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
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
Definitions
- the invention relates to the use of a composition for improving memory function, in a subject with a mini-mental state examination of 24-26.
- Memory impairment is a serious shortcoming in many humans, particularly those suffering from Alzheimer's disease and/or elderly. Such impairments often have serious consequences, such as reduced quality of life, difficulties in performing the activities of daily living, potentially resulting in hospitalization or institutionalization.
- Nutritional therapy is particularly desired in subjects who have relatively mild symptoms of memory impairment, i.e. subjects with a mini-mental state examination score (MMSE) of 24 to 26.
- MMSE mini-mental state examination score
- the present inventors have recognized that in this particular subgroup memory improvement has enormous effect for the subject activities of daily living and quality of life.
- This subgroup of subjects is distinct in that the pathological pathways have just started to develop.
- any score of 27 or higher is effectively normal.
- 20-26 indicates mild dementia, 10-19 moderate dementia, and below 10 severe dementia. It was the present inventors' belief that within the group of 20-26, the memory impairment in the sub-group of 24-26 may even be reversible, as the pathological pathways have just started to develop.
- the subgroup of subjects with a MMSE score of 24 to 26 comprises two populations. Firstly, it comprises those subjects who do not receive medication for memory impairment, i.e. the drug na ⁇ ve subjects.
- the treatment of this subgroup is particularly preferred as in these subjects the balance between side effects and benefits of pharmaceutical intervention is still negative. Providing nutritional therapy to these subjects is desired because of the relative lack of negative side effects.
- the subgroup of subjects with a MMSE score of 24 to 26 comprises a population of subjects with a very mild form of Alzheimer's Disease. Memory improvement through nutritional therapy is particularly desired in subjects with a very mild form of Alzheimer's Disease. If improvement of memory function could be achieved pharmaceutical intervention could be reduced or even postponed if significant improvements are observed.
- the present inventors surprisingly found, through clinical study, that administration of a composition containing (a) uridine or uridine phosphate; and (b) docosahexaenoic acid and/or eicosapentaenoic acid showed a significant improvement of memory function in subjects with a MMSE of 24 to 26. Compliance and tolerability were very high and side effects were relatively low. It was particularly surprising that the present clinical data showed an actual improvement in memory function, more than just a reduction in the rate of decline in memory function. Additionally it was found that in this subgroup the delayed recall function was significantly improved. The results of the clinical study are summarized in the examples.
- composition comprising:
- the present invention relates to subjects with a mini-mental state examination of 24, 25 or 26, i.e. of 24-26.
- the mini-mental state examination is a brief 30-point questionnaire test that is used to assess cognition. In the time span of about 10 minutes it samples various functions including memory and orientation.
- the MMSE test includes simple questions and problems in a number of areas: the time and place of the test, repeating lists of words, language use and comprehension, and basic motor skills. Any score of 27 or higher (out of 30) is effectively normal; 20-26 indicates mild dementia; 10-19 moderate dementia, and below 10 severe dementia.
- the MMSE is a standardized test.
- the subjects as treated in the present invention have a mini-mental state examination score of 24-26 and are preferably drug na ⁇ ve and/or suffer from a very mild form of Alzheimer's disease, preferably drug na ⁇ ve subjects with a very mild Alzheimer's disease and a MMSE of 24-26.
- drug na ⁇ ve refers to subjects who do not ingest one or more of cholinesterase inhibitors, N-methyl-D-aspartate (NMDA) antagonists and ginkgo biloba. In the clinical study presented here, it was found that the present composition is effective in drug na ⁇ ve subjects.
- the subject is preferably a human, preferably an elderly human, preferably at least 50 years of age.
- the present invention relates to use of the present composition for (i) the improvement of memory and/or (ii) treatment and/or prevention of impaired memory function.
- the present invention provides a method for (i) the improvement of memory and/or (ii) treatment and/or prevention of impaired memory function in a subject in need thereof, said method comprising the administration of the present composition to said subject.
- the present invention relates to the treatment of an impaired memory function. It was found that the memory function actually improved when the present composition was administered to the subject.
- the memory function of a human subject can suitably be determined using the (modified) ADAS-cog, Wechsler Memory Scale, WMS revised.
- Delayed recall function can be measured by a prose recall task 30-minute delay interval. Delayed recall of a prose passage is not a measure to differentiate clearly between very mild dementia of the Alzheimer type and normal ageing.
- the present composition can also advantageously help subjects not (yet) suffering from Alzheimer's disease in improving the delayed recall function.
- the invention provides a method for improving delayed recall and/or the treatment and/or prevention of an impaired delayed recall function.
- the present composition comprises uridine and/or uridine phosphate.
- the present composition comprises one or more uridine phosphates selected from uridine monophosphate (UMP), uridine diphosphate (UDP) and uridine triphosphate (UTP).
- UMP uridine monophosphate
- UDP uridine diphosphate
- UDP uridine triphosphate
- the present composition comprises UMP.
- at least 50 wt. % of the uridine in the present composition is provided by UMP, more preferably at least 75 wt. %, most preferably at least 95 wt. %.
- the present method preferably comprises the administration of uridine (the cumulative amount of uridine, deoxyuridine, uridine phosphates, uracil and acylated uridine derivatives) in an amount of 0.08-3 g per day, preferably 0.1-2 g per day, more preferably 0.2-1 g per day.
- the present method preferably comprises the administration of a composition comprising uridine in an amount of 0.08-3 g UMP per 100 ml liquid product, preferably 0.1-2 g UMP per 100 ml liquid product, more preferably 0.2-1 g per 100 ml liquid product.
- a composition comprising uridine in an amount of 0.08-3 g UMP per 100 ml liquid product, preferably 0.1-2 g UMP per 100 ml liquid product, more preferably 0.2-1 g per 100 ml liquid product.
- 1-37.5 mg UMP per kilogram body weight is administered per day.
- the required dosages of the equivalents on a weight base can be calculated from the dose for UMP by taking equimolar amounts using the molecular weight of the equivalent and of UMP, the latter being 324 Dalton.
- the present composition preferably comprises at least docosahexaenoic acid (22:6 ⁇ -3; DHA) and/or eicosapentaenoic acid (20:5 ⁇ -3; EPA), preferably DHA and EPA.
- DHA and/or EPA is preferably provided as triglycerides, diglycerides, monoglycerides, free fatty acids or their salts or esters, phospholipids, lysophospholipids, glycerol ethers, lipoproteins, ceramides, glycolipids or combinations thereof.
- the present composition comprises at least DHA in triglyceride form.
- the present method preferably comprises the administration of 400-5000 mg (DHA+EPA) per day, more preferably 500-3000 mg per day, most preferably 1000-2500 mg per day.
- the proportion of (DHA+EPA) of the total fatty acids present in the composition is preferably 5-50 wt. %, more preferably 10-45 wt. %, most preferably 15-40 wt. %.
- the present method preferably comprises the administration of DHA, preferably in an amount of 300-4000 mg per day, more preferably 500-2500 mg per day.
- the present composition preferably contains a very low amount of arachidonic acid (AA).
- the weight ratio DHA/AA in the present composition is at least 5, preferably at least 10, more preferably at least 15, preferably up to e.g. 60 or up to 30.
- the present method preferably comprises the administration of a composition comprising less than 5 wt. % arachidonic acid based on total fatty acids, more preferably below 2.5 wt. %, e.g. down to 0.5 wt %.
- the ratio omega-6/omega-3 fatty acids in the present product is preferably below 0.5, more preferably below 0.2, e.g. down to 0.05 or to 0.1.
- the ratio ⁇ -6/ ⁇ -3 fatty acids (C 20 and higher) in the present product is preferably below 0.3, more preferably below 0.15, e.g. down to 0.03 or to 0.06.
- an amount per day as described herein means an amount in a daily dosage unit provided by the composition of the invention. Such a daily dosage unit may be a single dosage, but it may also be divided over two or three, or even more daily servings. If the composition, as according to a preferred embodiment, is intended for administration as a single unit, the amounts per day as described herein, are preferably the amounts present in the (preferably packaged) composition unit. Treatment preferably involves administration once, twice or three times per day, more preferably once per day for a period of at least 3 weeks.
- the present composition preferably comprises 1-40 wt. % DHA based on total fatty acids, preferably 3-36 wt. % DHA based on total fatty acids, more preferably 10-30 wt. % DHA based on total fatty acids.
- the present composition preferably comprises 0.5-20 wt. % EPA based on total fatty acids, preferably 2-10 wt. % EPA based on total fatty acids, more preferably 5-10wt. % EPA based on total fatty acids.
- the above-mentioned amounts take into account and optimise several aspects, including taste (e.g. too high LCP levels reduce taste, resulting in a reduced compliance).
- the present composition preferably contains at least one oil selected from fish oil, algae oil and eggs lipids.
- the present composition contains fish oil comprising DHA and EPA.
- the present composition preferably comprises saturated and/or mono-unsaturated fatty acids.
- the amount of saturated fatty acids is preferably 6-60 wt. % based on total fatty acids, preferably 12-40 wt. %, more preferably 20-40 wt. % based on total fatty acids.
- the amount of C14:0 (myristic acid)+C16:0 (palmitic acid) is preferably 5-50 wt. %, preferably 8-36, more preferably 15-30 wt. % wt. % based on total fatty acids.
- the total amount of monounsaturated fatty acids, such as oleic acid and palmitoleic acid is preferably between 5 and 40 wt. %, more preferably between 15 and 30 wt. %. A composition with these preferred amounts was found to be very effective.
- the present composition preferably comprises phospholipids, preferably 0.1-50 wt. % phospholipids based on total weight of lipids, more preferably 0.5-20 wt. %, more preferably between 1 and 10% wt. %, most preferably between 1 and 5 wt. % based on total weight of lipids.
- the total amount of lipids is preferably between 10 and 30 wt. % on dry matter, and/or between 2 and 10 g lipid per 100 ml for a liquid composition.
- the composition preferably comprises between 0.01 and 1 gram lecithin per 100 ml, more preferably between 0.05 and 0.5 gram lecithin per 100 ml. A composition with these preferred amounts was found to be very effective.
- the present composition contains choline and/or phosphatidylcholine.
- the present method preferably comprises the administration of more than 50 mg choline per day, preferably 80-2000 mg choline per day, more preferably 120-1000 mg choline per day, most preferably 150-600 mg choline per day.
- the present composition preferably comprises 50 mg to 3 gram choline per 100 ml of the liquid formula, preferably 200 mg-1000 mg choline/100 ml.
- the composition may advantageously contain vitamins, preferably vitamin C, vitamin E and B vitamins, more preferably vitamin C, vitamin E, vitamin B6, vitamin B12 and folic acid.
- vitamin B12 and folate are included.
- the present composition preferably comprises 50-1000 ⁇ g folic acid, more preferably 150-750 ⁇ g, most preferably 200-500 ⁇ g folic acid, per 100 ml liquid product.
- the present method preferably comprises the administration of 50-1000 ⁇ g folic acid per day, more preferably 150-750 ⁇ g, most preferably 200-500 ⁇ g folic acid per day.
- the present composition preferably comprises 0.5-15 ⁇ g vitamin B12, more preferably 1-10 ⁇ g, most preferably 1.5-5 ⁇ g vitamin B12, per 100 ml liquid product.
- the present method preferably comprises the administration 0.5-15 ⁇ g vitamin B12 per day, more preferably 1-10 ⁇ g, most preferably 1.5-5 ⁇ g vitamin B12 per day.
- the present composition comprises one or more of phospholipids, choline, vitamin E, vitamin C, selenium, vitamin B12, vitamin B6 and folic acid, more preferably phospholipids, choline, vitamin E, vitamin C, selenium, vitamin B12, vitamin B6 and folic acid.
- the present composition is preferably a ready-to-use liquid, solid, or semi-liquid product.
- the present composition is preferably enterally administered, more preferably orally. Most preferably the present composition is administered through a straw.
- the daily liquid amount is preferably between 75 and 200 ml per day or per unit, most preferably between 90 and 150 ml/day.
- the present composition is preferably provided in the form of a drink capable of being ingested through a straw.
- the composition according to the invention preferably has a low viscosity, preferably a viscosity between 1 and 2000 mPa.s measured at a shear rate of 100 sec ⁇ 1 at 20° C., more preferably a viscosity between 1 and 100 mPa.s measured at a shear rate of 100 sec ⁇ 1 at 20° C. More preferably, the present composition is provided in the form of a drink capable of being ingested through a straw which makes the product even easier to ingest and improves compliance.
- the present composition has a viscosity of 1-80 mPas at a shear rate of 100 per sec at 20° C., more preferably of 1-40 mPas at a shear rate of 100 per sec at 20° C.
- These viscosity measurements may for instance be performed using plate and cone geometry.
- the present composition preferably has an osmolality of 300 to 800 mOsm/kg.
- the energy density of the product is preferably not so high that it interferes with normal eating habits.
- the present product preferably contains between 0.2 and 3 kcal/ml, more preferably between 0.5 and 2, between 0.7 and 1.5 kcal/ml.
- the present composition contains digestible carbohydrates.
- the present composition preferably contains between 1 and 50 gram digestible carbohydrates per 100 ml of a liquid product, more preferably between 5 and 30 grams per 100 ml, more preferably 10-30 grams carbohydrates per 100 ml.
- the total amount of digestible carbohydrates is preferably between 25 and 80 wt. % on dry matter, preferably 40-80 wt. % based on dry matter.
- the present composition may further comprise protein, preferably 0.5-10 g protein per 100 ml, more preferably 1-6 gram protein per 100 ml, most preferably 2-6 gram protein/100 ml.
- protein preferably 0.5-10 g protein per 100 ml, more preferably 1-6 gram protein per 100 ml, most preferably 2-6 gram protein/100 ml.
- the present composition contain at least 80 wt. % milk derived protein (e.g. whey and/or casein) based on total protein. Proteins enable the manufacturing of palatable products, especially for frail elderly.
- Fat includes 1.5 g DHA+EPA, and 106 mg phospholipids (soy lecithin); Choline 400 mg; UMP (uridine monophosphate) 625 mg; Vitamin E 40 mg ⁇ -TE; Vitamin C 80 mg; Selenium 60 ⁇ g; Vitamin B12 3 ⁇ g; Vitamin B6 1 mg; Folic acid 400 ⁇ g.
- AD Alzheimer's disease
- Drug na ⁇ ve very mild AD subjects with a MMSE of 24-26 were randomly allocated in a double-blind 12 weeks study to receive a 125 ml (125 kcal) once-a-day milk-based drink with: (a) the formula according to example 1 (active product) or (b) an iso-caloric control drink according to example 1, but without EPA, DHA, phospholipids, choline, UMP, vitamin E, vitamin C, selenium, vitamin B12, vitamin B6 and folic acid (control product).
- Outcome measure was a (delayed) verbal memory task (derived from Wechsler Memory Scale-revised).
Abstract
The invention thus pertains to the use of a composition comprising: (a) uridine or uridine phosphate; and (b) docosahexaenoic acid and/or eicosapentaenoic acid, for improving memory and/or the treatment or prevention of impaired memory function, in a subject with a mini-mental state examination of 24-26, wherein said composition is enterally administered to the subject. In the MMSE test, any score of 27 or higher (out of 30) is effectively normal. In the patients with dementia, 20-26 indicates mild dementia, 10-19 moderate dementia, and below 10 severe dementia. It was the present inventors' belief that within the group of 20-26, the memory impairment in the sub-group of 24-26 may even be reversible, as the pathological pathways have just started to develop. In this group of subjects the pathological pathways have just started to develop. Clinical studies show excellent results for this subgroup.
Description
- The invention relates to the use of a composition for improving memory function, in a subject with a mini-mental state examination of 24-26.
- Memory impairment is a serious shortcoming in many humans, particularly those suffering from Alzheimer's disease and/or elderly. Such impairments often have serious consequences, such as reduced quality of life, difficulties in performing the activities of daily living, potentially resulting in hospitalization or institutionalization.
- Several treatments have been suggested for the improvement of memory function in subjects. However, very few have been proven effective. Moreover, the administration of several nutritional ingredients has also been suggested.
- Nutritional therapy is particularly desired in subjects who have relatively mild symptoms of memory impairment, i.e. subjects with a mini-mental state examination score (MMSE) of 24 to 26. The present inventors have recognized that in this particular subgroup memory improvement has enormous effect for the subject activities of daily living and quality of life. This subgroup of subjects is distinct in that the pathological pathways have just started to develop. In the MMSE test, any score of 27 or higher (out of 30) is effectively normal. In the patients with dementia, 20-26 indicates mild dementia, 10-19 moderate dementia, and below 10 severe dementia. It was the present inventors' belief that within the group of 20-26, the memory impairment in the sub-group of 24-26 may even be reversible, as the pathological pathways have just started to develop. It would be highly desired to improve the memory function of this subgroup of subjects, as this may delay the need or reduce the dosage of treatment with pharmaceutical drugs. Moreover, improvements in subjects with a MMSE of 24 to 26 can postpone the need for a subject to be hospitalized or institutionalized, enable a longer independent living, improve the quality of life or improve the ability to perform daily activities.
- The subgroup of subjects with a MMSE score of 24 to 26 comprises two populations. Firstly, it comprises those subjects who do not receive medication for memory impairment, i.e. the drug naïve subjects. The treatment of this subgroup is particularly preferred as in these subjects the balance between side effects and benefits of pharmaceutical intervention is still negative. Providing nutritional therapy to these subjects is desired because of the relative lack of negative side effects. For subjects with a MMSE of 24 to 26 who are drug naïve, it is particularly important to develop a therapy which delays the point in time where pharmaceutical drugs have to be administered.
- Secondly, the subgroup of subjects with a MMSE score of 24 to 26 comprises a population of subjects with a very mild form of Alzheimer's Disease. Memory improvement through nutritional therapy is particularly desired in subjects with a very mild form of Alzheimer's Disease. If improvement of memory function could be achieved pharmaceutical intervention could be reduced or even postponed if significant improvements are observed.
- It is however particularly difficult to find a (nutritional) composition which effectively improves memory function in the group with a MMSE of 24 to 26 as the pathological pathways have only started to develop and symptoms are very mild. Detecting differences between control and treatment group is particularly difficult, and hence effective treatment requires intensive testing.
- The present inventors surprisingly found, through clinical study, that administration of a composition containing (a) uridine or uridine phosphate; and (b) docosahexaenoic acid and/or eicosapentaenoic acid showed a significant improvement of memory function in subjects with a MMSE of 24 to 26. Compliance and tolerability were very high and side effects were relatively low. It was particularly surprising that the present clinical data showed an actual improvement in memory function, more than just a reduction in the rate of decline in memory function. Additionally it was found that in this subgroup the delayed recall function was significantly improved. The results of the clinical study are summarized in the examples.
- The invention thus pertains to the use of a composition comprising:
-
- a. uridine or uridine phosphate; and
- b. docosahexaenoic acid and/or eicosapentaenoic acid
for improving memory and/or the treatment or prevention of impaired memory function, in a subject with a mini-mental state examination of 24-26, wherein said composition is enterally administered to the subject.
- The present invention relates to subjects with a mini-mental state examination of 24, 25 or 26, i.e. of 24-26. The mini-mental state examination (MMSE) is a brief 30-point questionnaire test that is used to assess cognition. In the time span of about 10 minutes it samples various functions including memory and orientation. The MMSE test includes simple questions and problems in a number of areas: the time and place of the test, repeating lists of words, language use and comprehension, and basic motor skills. Any score of 27 or higher (out of 30) is effectively normal; 20-26 indicates mild dementia; 10-19 moderate dementia, and below 10 severe dementia. The MMSE is a standardized test. Copyrights prevent the inventors from including a copy of the questionnaire into the specification, but it is readily accessible on the internet and available through copyright owner Psychological Assessment Resources (PAR). It is first introduced by Folstein et al. (Psych Res 12:189, 1975), and is widely used with small modifications to assess cognition.
- The subjects as treated in the present invention have a mini-mental state examination score of 24-26 and are preferably drug naïve and/or suffer from a very mild form of Alzheimer's disease, preferably drug naïve subjects with a very mild Alzheimer's disease and a MMSE of 24-26. The term “drug naïve” as used in the present invention refers to subjects who do not ingest one or more of cholinesterase inhibitors, N-methyl-D-aspartate (NMDA) antagonists and ginkgo biloba. In the clinical study presented here, it was found that the present composition is effective in drug naïve subjects. The subject is preferably a human, preferably an elderly human, preferably at least 50 years of age.
- The present invention relates to use of the present composition for (i) the improvement of memory and/or (ii) treatment and/or prevention of impaired memory function. Alternatively, the present invention provides a method for (i) the improvement of memory and/or (ii) treatment and/or prevention of impaired memory function in a subject in need thereof, said method comprising the administration of the present composition to said subject. Particularly, the present invention relates to the treatment of an impaired memory function. It was found that the memory function actually improved when the present composition was administered to the subject. The memory function of a human subject can suitably be determined using the (modified) ADAS-cog, Wechsler Memory Scale, WMS revised.
- It was particularly found that in these subjects the delayed recall function was improved. Delayed recall function can be measured by a prose recall task 30-minute delay interval. Delayed recall of a prose passage is not a measure to differentiate clearly between very mild dementia of the Alzheimer type and normal ageing. Hence, the present composition can also advantageously help subjects not (yet) suffering from Alzheimer's disease in improving the delayed recall function. Hence, in a preferred embodiment the invention provides a method for improving delayed recall and/or the treatment and/or prevention of an impaired delayed recall function.
- Preferably the present composition comprises uridine and/or uridine phosphate. Preferably the present composition comprises one or more uridine phosphates selected from uridine monophosphate (UMP), uridine diphosphate (UDP) and uridine triphosphate (UTP).
- Most preferably the present composition comprises UMP. Preferably at least 50 wt. % of the uridine in the present composition is provided by UMP, more preferably at least 75 wt. %, most preferably at least 95 wt. %. The present method preferably comprises the administration of uridine (the cumulative amount of uridine, deoxyuridine, uridine phosphates, uracil and acylated uridine derivatives) in an amount of 0.08-3 g per day, preferably 0.1-2 g per day, more preferably 0.2-1 g per day. The present method preferably comprises the administration of a composition comprising uridine in an amount of 0.08-3 g UMP per 100 ml liquid product, preferably 0.1-2 g UMP per 100 ml liquid product, more preferably 0.2-1 g per 100 ml liquid product. Preferably 1-37.5 mg UMP per kilogram body weight is administered per day. The required dosages of the equivalents on a weight base can be calculated from the dose for UMP by taking equimolar amounts using the molecular weight of the equivalent and of UMP, the latter being 324 Dalton.
- Docosahexaenoic Acid and/or Eicosapentaenoic Acid
- The present composition preferably comprises at least docosahexaenoic acid (22:6 ω-3; DHA) and/or eicosapentaenoic acid (20:5 ω-3; EPA), preferably DHA and EPA. The DHA and/or EPA is preferably provided as triglycerides, diglycerides, monoglycerides, free fatty acids or their salts or esters, phospholipids, lysophospholipids, glycerol ethers, lipoproteins, ceramides, glycolipids or combinations thereof. Preferably, the present composition comprises at least DHA in triglyceride form.
- The present method preferably comprises the administration of 400-5000 mg (DHA+EPA) per day, more preferably 500-3000 mg per day, most preferably 1000-2500 mg per day. The proportion of (DHA+EPA) of the total fatty acids present in the composition is preferably 5-50 wt. %, more preferably 10-45 wt. %, most preferably 15-40 wt. %. The present method preferably comprises the administration of DHA, preferably in an amount of 300-4000 mg per day, more preferably 500-2500 mg per day.
- The present composition preferably contains a very low amount of arachidonic acid (AA). Preferably the weight ratio DHA/AA in the present composition is at least 5, preferably at least 10, more preferably at least 15, preferably up to e.g. 60 or up to 30. The present method preferably comprises the administration of a composition comprising less than 5 wt. % arachidonic acid based on total fatty acids, more preferably below 2.5 wt. %, e.g. down to 0.5 wt %. The ratio omega-6/omega-3 fatty acids in the present product is preferably below 0.5, more preferably below 0.2, e.g. down to 0.05 or to 0.1. The ratio ω-6/ω-3 fatty acids (C 20 and higher) in the present product is preferably below 0.3, more preferably below 0.15, e.g. down to 0.03 or to 0.06.
- An amount per day as described herein means an amount in a daily dosage unit provided by the composition of the invention. Such a daily dosage unit may be a single dosage, but it may also be divided over two or three, or even more daily servings. If the composition, as according to a preferred embodiment, is intended for administration as a single unit, the amounts per day as described herein, are preferably the amounts present in the (preferably packaged) composition unit. Treatment preferably involves administration once, twice or three times per day, more preferably once per day for a period of at least 3 weeks.
- The present composition preferably comprises 1-40 wt. % DHA based on total fatty acids, preferably 3-36 wt. % DHA based on total fatty acids, more preferably 10-30 wt. % DHA based on total fatty acids. The present composition preferably comprises 0.5-20 wt. % EPA based on total fatty acids, preferably 2-10 wt. % EPA based on total fatty acids, more preferably 5-10wt. % EPA based on total fatty acids. The above-mentioned amounts take into account and optimise several aspects, including taste (e.g. too high LCP levels reduce taste, resulting in a reduced compliance).
- The present composition preferably contains at least one oil selected from fish oil, algae oil and eggs lipids. Preferably the present composition contains fish oil comprising DHA and EPA.
- The present composition preferably comprises saturated and/or mono-unsaturated fatty acids. The amount of saturated fatty acids is preferably 6-60 wt. % based on total fatty acids, preferably 12-40 wt. %, more preferably 20-40 wt. % based on total fatty acids. In particular the amount of C14:0 (myristic acid)+C16:0 (palmitic acid) is preferably 5-50 wt. %, preferably 8-36, more preferably 15-30 wt. % wt. % based on total fatty acids. The total amount of monounsaturated fatty acids, such as oleic acid and palmitoleic acid, is preferably between 5 and 40 wt. %, more preferably between 15 and 30 wt. %. A composition with these preferred amounts was found to be very effective.
- Preferably, the present composition preferably comprises phospholipids, preferably 0.1-50 wt. % phospholipids based on total weight of lipids, more preferably 0.5-20 wt. %, more preferably between 1 and 10% wt. %, most preferably between 1 and 5 wt. % based on total weight of lipids. The total amount of lipids is preferably between 10 and 30 wt. % on dry matter, and/or between 2 and 10 g lipid per 100 ml for a liquid composition. The composition preferably comprises between 0.01 and 1 gram lecithin per 100 ml, more preferably between 0.05 and 0.5 gram lecithin per 100 ml. A composition with these preferred amounts was found to be very effective.
- Preferably the present composition contains choline and/or phosphatidylcholine. The present method preferably comprises the administration of more than 50 mg choline per day, preferably 80-2000 mg choline per day, more preferably 120-1000 mg choline per day, most preferably 150-600 mg choline per day. The present composition preferably comprises 50 mg to 3 gram choline per 100 ml of the liquid formula, preferably 200 mg-1000 mg choline/100 ml.
- The composition may advantageously contain vitamins, preferably vitamin C, vitamin E and B vitamins, more preferably vitamin C, vitamin E, vitamin B6, vitamin B12 and folic acid. Advantageously, vitamin B12 and folate are included. The present composition preferably comprises 50-1000 μg folic acid, more preferably 150-750 μg, most preferably 200-500 μg folic acid, per 100 ml liquid product. The present method preferably comprises the administration of 50-1000 μg folic acid per day, more preferably 150-750 μg, most preferably 200-500 μg folic acid per day. The present composition preferably comprises 0.5-15 μg vitamin B12, more preferably 1-10 μg, most preferably 1.5-5 μg vitamin B12, per 100 ml liquid product. The present method preferably comprises the administration 0.5-15 μg vitamin B12 per day, more preferably 1-10 μg, most preferably 1.5-5 μg vitamin B12 per day.
- Preferably the present composition comprises one or more of phospholipids, choline, vitamin E, vitamin C, selenium, vitamin B12, vitamin B6 and folic acid, more preferably phospholipids, choline, vitamin E, vitamin C, selenium, vitamin B12, vitamin B6 and folic acid.
- The present composition is preferably a ready-to-use liquid, solid, or semi-liquid product. The present composition is preferably enterally administered, more preferably orally. Most preferably the present composition is administered through a straw. When it is a ready-to-use liquid, the daily liquid amount is preferably between 75 and 200 ml per day or per unit, most preferably between 90 and 150 ml/day.
- The subjects that can benefit from the method and composition of the invention often experience problems with eating. Their sensory capabilities and/or control of muscles can become imparted, as well as in some instances their ambition to apply proper eating habits. Swallowing and/or mastication may be problematic. Hence, the present composition is preferably provided in the form of a drink capable of being ingested through a straw.
- The composition according to the invention preferably has a low viscosity, preferably a viscosity between 1 and 2000 mPa.s measured at a shear rate of 100 sec−1 at 20° C., more preferably a viscosity between 1 and 100 mPa.s measured at a shear rate of 100 sec−1 at 20° C. More preferably, the present composition is provided in the form of a drink capable of being ingested through a straw which makes the product even easier to ingest and improves compliance. In a preferred embodiment the present composition has a viscosity of 1-80 mPas at a shear rate of 100 per sec at 20° C., more preferably of 1-40 mPas at a shear rate of 100 per sec at 20° C. These viscosity measurements may for instance be performed using plate and cone geometry.
- To be optimally accepted by the subject, the present composition preferably has an osmolality of 300 to 800 mOsm/kg. However, the energy density of the product is preferably not so high that it interferes with normal eating habits. When in liquid form, the present product preferably contains between 0.2 and 3 kcal/ml, more preferably between 0.5 and 2, between 0.7 and 1.5 kcal/ml.
- Advantageously the present composition contains digestible carbohydrates. The present composition preferably contains between 1 and 50 gram digestible carbohydrates per 100 ml of a liquid product, more preferably between 5 and 30 grams per 100 ml, more preferably 10-30 grams carbohydrates per 100 ml. The total amount of digestible carbohydrates is preferably between 25 and 80 wt. % on dry matter, preferably 40-80 wt. % based on dry matter.
- The present composition may further comprise protein, preferably 0.5-10 g protein per 100 ml, more preferably 1-6 gram protein per 100 ml, most preferably 2-6 gram protein/100 ml. Preferably the present composition contain at least 80 wt. % milk derived protein (e.g. whey and/or casein) based on total protein. Proteins enable the manufacturing of palatable products, especially for frail elderly.
- Packaged composition for the comprising per 125 ml:
- Energy 125 kcal; Protein 3.9 g; Carbohydrate 16.5 g; Fat 4.9 g.
- Fat includes 1.5 g DHA+EPA, and 106 mg phospholipids (soy lecithin); Choline 400 mg; UMP (uridine monophosphate) 625 mg; Vitamin E 40 mg α-TE; Vitamin C 80 mg; Selenium 60 μg; Vitamin B12 3 μg; Vitamin B6 1 mg; Folic acid 400 μg.
- Minerals and trace elements: Sodium 125 mg; Potassium 187.5 mg; Chloride 156.3 mg; Calcium 100 mg; Phosphorus 87.5 mg; Magnesium 25 mg; Iron 2 mg; Zinc 1.5 mg; Copper 225 μg; Manganese 0.41 mg; Molybdenum 12.5 μg; Chromium 8.4 μg; Iodine 16.3 μg. Vitamins: Vit. A 200 μg-RE; vit. D3 0.9 μg; vit. K 6.6 μg; Thiamin (B1) 0.19 mg; Riboflavin (B2) 0.2 mg; Niacin (B3) 2.25 mg-NE; Pantothenic acid (B5) 0.66 mg; Biotin 5 μg.
- Increasing evidence shows a role of nutrients in subjects with impaired memory function. The present study was done to assess the effect of an intervention with a medical food on memory in drug naïve, very mild Alzheimer's disease (AD) subjects. Drug naïve very mild AD subjects with a MMSE of 24-26 were randomly allocated in a double-blind 12 weeks study to receive a 125 ml (125 kcal) once-a-day milk-based drink with: (a) the formula according to example 1 (active product) or (b) an iso-caloric control drink according to example 1, but without EPA, DHA, phospholipids, choline, UMP, vitamin E, vitamin C, selenium, vitamin B12, vitamin B6 and folic acid (control product).
- Outcome measure was a (delayed) verbal memory task (derived from Wechsler Memory Scale-revised).
- At baseline, there was no significant difference between the group treated with the active product and the group treated with the control product. However, there was a significant difference between the two groups in the change in the delayed verbal memory task (derived from Wechsler Memory scale-revised (WMS-r)) between baseline and after 12 weeks of treatment. The group receiving control product (n=66) had an average decline of −0.164 with a 95% confidence interval including zero (−0.938 to 0.610) whereas the group receiving active product (n=60) had an average improvement of 0.983 points on the delayed verbal memory scale derived from WMS-r with a 95% confidence interval above zero (0.214 to 1.752).
- This study demonstrates that intervention with the active product for 12 weeks improves memory, particularly delayed recall function in subjects with MMSE of 24-26 (see table 1).
-
TABLE 1 Delayed verbal memory score Group Subjects with MMSE 24-26 (WMS-r) Control 66 −0.164 Treatment 60 +0.983
Claims (16)
1.-7. (canceled)
8. An enteral composition comprising:
a. uridine or uridine phosphate; and
b. docosahexaenoic acid and/or eicosapentaenoic acid.
9. The composition according to claim 8 , further comprising phospholipids, choline, vitamin E, vitamin C, selenium, vitamin B12, vitamin B6 and folic acid.
10. The composition according to claim 8 , comprising 0.1-2 g uridine, calculated as uridine monophosphate, per daily dosage unit.
11. The composition according to claim 8 , comprising 400-5000 mg of the sum of DHA and EPA per daily dosage unit.
12. The composition according to claim 10 , comprising 400-5000 mg of the sum of DHA and EPA per daily dosage unit.
13. The composition according to claim 8 , comprising 1-50 gram digestible carbohydrates per 100 ml.
14. The composition according to claim 8 , comprising 0.5-10 g protein per 100 ml.
15. The composition according to claim 8 , comprising 0.2-3 kcal/ml.
16. The composition according to claim 8 , comprising 1-50 gram digestible carbohydrates per 100 ml, 0.5-10 g protein per 100 ml, and 0.2-3 kcal/ml.
17. The composition according to claim 8 , being a liquid product, having a viscosity between 1 and 100 mPa.s as measured at a shear rate of 100 s−1 at 20° C.
18. A method for (i) improving delayed recall function and/or (ii) the treatment and/or prevention of an impaired delayed recall function of a subject, comprising enterally administering to the subject a composition comprising:
a. uridine or uridine phosphate; and
b. docosahexaenoic acid and/or eicosapentaenoic acid.
19. The method according to claim 18 , wherein the subject has a mini-mental state examination of 24-26.
20. The method according to claim 18 , wherein the composition is enterally administered to the subject at least one time per day for a period of at least 3 weeks.
21. A method for improving memory and/or treatment or prevention of impaired memory function in a subject with a mini-mental state examination of 24 or 25, comprising enterally administering to the subject a composition comprising:
a. uridine or uridine phosphate; and
b. docosahexaenoic acid and/or eicosapentaenoic acid.
22. The method according to claim 21 , wherein the composition is enterally administered to the subject at least one time per day for a period of at least 3 weeks.
Applications Claiming Priority (11)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
PCT/NL2007/050307 WO2009002146A1 (en) | 2007-06-26 | 2007-06-26 | Supporting activities of daily living |
NLPCT/NL2007/050306 | 2007-06-26 | ||
NLPCT/NL2007/050307 | 2007-06-26 | ||
PCT/NL2007/050306 WO2009002145A1 (en) | 2007-06-26 | 2007-06-26 | Lipid composition for improving function of brain functioning |
PCT/NL2007/050310 WO2009002148A1 (en) | 2007-06-27 | 2007-06-27 | Food composition for prodromal dementia patients |
NLPCT/NL2007/050310 | 2007-06-27 | ||
EP07123811.7 | 2007-12-20 | ||
EP07123811 | 2007-12-20 | ||
NLPCT/NL2008/050124 | 2008-03-04 | ||
PCT/NL2008/050124 WO2009082203A1 (en) | 2007-12-20 | 2008-03-04 | Liquid nucleotides/nucleosides-containing product |
PCT/NL2008/050411 WO2009002166A1 (en) | 2007-06-26 | 2008-06-20 | Improving memory in subjects with mini-mental state examination of 24-26 |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/NL2008/050411 A-371-Of-International WO2009002166A1 (en) | 2007-06-26 | 2008-06-20 | Improving memory in subjects with mini-mental state examination of 24-26 |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US16/696,941 Continuation US11395810B2 (en) | 2007-06-26 | 2019-11-26 | Memory in subjects with mini-mental state examination of 24-26 |
Publications (1)
Publication Number | Publication Date |
---|---|
US20100331258A1 true US20100331258A1 (en) | 2010-12-30 |
Family
ID=41580940
Family Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US12/666,611 Abandoned US20100331258A1 (en) | 2007-06-26 | 2008-06-20 | memory in subjects with mini-mental state examination of 24-26 |
US16/696,941 Active 2028-08-23 US11395810B2 (en) | 2007-06-26 | 2019-11-26 | Memory in subjects with mini-mental state examination of 24-26 |
US17/751,704 Pending US20220280466A1 (en) | 2007-06-26 | 2022-05-24 | Memory in subjects with mini-mental state examination of 24-26 |
Family Applications After (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US16/696,941 Active 2028-08-23 US11395810B2 (en) | 2007-06-26 | 2019-11-26 | Memory in subjects with mini-mental state examination of 24-26 |
US17/751,704 Pending US20220280466A1 (en) | 2007-06-26 | 2022-05-24 | Memory in subjects with mini-mental state examination of 24-26 |
Country Status (15)
Country | Link |
---|---|
US (3) | US20100331258A1 (en) |
EP (2) | EP2689782B1 (en) |
JP (2) | JP5841723B2 (en) |
CN (2) | CN101765427A (en) |
AU (1) | AU2008269728B2 (en) |
BR (1) | BRPI0813770B1 (en) |
CA (1) | CA2692309C (en) |
DK (1) | DK2170316T3 (en) |
ES (2) | ES2808406T3 (en) |
MX (1) | MX2010000224A (en) |
NZ (2) | NZ582329A (en) |
PL (1) | PL2170316T3 (en) |
PT (1) | PT2170316E (en) |
RU (2) | RU2529815C2 (en) |
WO (1) | WO2009002166A1 (en) |
Cited By (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20100323982A1 (en) * | 2007-06-27 | 2010-12-23 | N.V. Nutricia | Food composition for prodromal dementia patients |
US20100331275A1 (en) * | 2007-06-26 | 2010-12-30 | Martine Groenendijk | Supporting activities of daily living |
US20110009357A1 (en) * | 2007-06-26 | 2011-01-13 | N.V. Nutricia | Lipid composition for improving brain function |
US20110105594A1 (en) * | 2007-12-20 | 2011-05-05 | N.V. Nutricia | Palatable nutritional composition comprising a nucleotide and/or a nucleoside and a taste masking agent |
US20110158188A1 (en) * | 2008-02-01 | 2011-06-30 | Research In Motion Limited | System and Method for Uplink Timing Synchronization in Conjunction With Discontinuous Reception |
US20130331352A1 (en) * | 2010-12-28 | 2013-12-12 | N.V. Nutricia | Combination of Components for the Prevention and Treatment of Frailty |
US20150044138A1 (en) * | 2012-03-02 | 2015-02-12 | N.V. Nutricia | Method for improving functional synaptic connectivity |
US11395810B2 (en) | 2007-06-26 | 2022-07-26 | N.V. Nutricia | Memory in subjects with mini-mental state examination of 24-26 |
Families Citing this family (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP2554057A4 (en) * | 2010-03-31 | 2013-12-18 | Vegenat S A | Enteral or oral food product intended, in particular, for nutrition and for the prevention and improvement of neurological alterations, neurodegenerative alterations or cognitive disorders |
WO2013066153A1 (en) * | 2011-10-31 | 2013-05-10 | N.V. Nutricia | Composition for improving neuropsychological test battery score |
WO2013066151A1 (en) * | 2011-10-31 | 2013-05-10 | N.V. Nutricia | Improving recognition |
WO2013066152A1 (en) | 2011-10-31 | 2013-05-10 | N.V. Nutricia | Method for improving executive function |
BR112014010166A8 (en) * | 2011-10-31 | 2017-06-20 | Nutricia Nv | use of a composition for the manufacture of a product to improve neuropsychological test battery scores, a method for assessing an individual's cognition and use of a composition for the manufacture of a product to treat an individual in need thereof |
WO2014171813A1 (en) * | 2013-04-17 | 2014-10-23 | N.V. Nutricia | Nutritional composition for improving brain function in phenylketonuria |
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 |
WO2017069613A1 (en) | 2015-10-23 | 2017-04-27 | N.V. Nutricia | Method for improving recognition and/or working memory in hyperphenylalanimenia and phenylketonuria patients |
RU2741495C2 (en) * | 2016-04-18 | 2021-01-26 | Н.В. Нютрисиа | Linoleic acid or alpha-linolenic acid for use in reducing cognitive disorders/early neurogenesis induced by early life stress |
CN108567792A (en) * | 2017-03-07 | 2018-09-25 | 上海泽生科技开发股份有限公司 | A kind of compound vitamin composition for treating Alzheimer disease |
MX2019010484A (en) | 2017-04-11 | 2019-10-17 | Nestle Sa | Omega-3 fatty acid and vitamin d levels to identify and attenuate cognitive aging in individuals. |
CN117337186A (en) * | 2021-05-17 | 2024-01-02 | 小野药品工业株式会社 | Composition for improving cognitive function |
WO2023041776A1 (en) | 2021-09-17 | 2023-03-23 | N.V. Nutricia | Solid composition suitable as a nutritional composition or supplement for animals that suffer from brain related disorders, decline or diseases |
Citations (17)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3600197A (en) * | 1968-08-27 | 1971-08-17 | Merck & Co Inc | Flavor enhancing compositions for foods and beverages |
US5378488A (en) * | 1993-06-10 | 1995-01-03 | Abbott Laboratories | Aseptic processing of infant formula |
US5886037A (en) * | 1996-11-20 | 1999-03-23 | N.V. Nutricia | Nutritional composition for the treatment of hypertriglyceridaemia and hyperchylomicronaemia |
US20030114415A1 (en) * | 2001-12-14 | 2003-06-19 | Wurtman Richard J. | Compositions and methods for treating and preventing memory impairment using citicoline |
US20040001817A1 (en) * | 2002-05-14 | 2004-01-01 | Giampapa Vincent C. | Anti-aging nutritional supplement |
US6689467B1 (en) * | 1998-12-23 | 2004-02-10 | Rhodia Chimie | Composition comprising an inorganic coating and a core comprising at least a polyhydroxyl compound |
US6835750B1 (en) * | 2000-05-01 | 2004-12-28 | Accera, Inc. | Use of medium chain triglycerides for the treatment and prevention of alzheimer's disease and other diseases resulting from reduced neuronal metabolism II |
US20050208179A1 (en) * | 2004-03-18 | 2005-09-22 | Albrecht Daniel S | Nutritional formula containing select carotenoid combinations |
US20060025376A1 (en) * | 2004-05-13 | 2006-02-02 | Wurtman Richard J | Uridine effects on dopamine release |
US20060241077A1 (en) * | 1998-07-31 | 2006-10-26 | Richard Wurtman | Methods and compositions for ameliorating or inhibiting decline in memory or intelligence or improving same |
US20070004670A1 (en) * | 1998-07-31 | 2007-01-04 | Richard Wurtman | Compositions containing citicoline, and methods of use thereof |
US20070140992A1 (en) * | 2005-12-21 | 2007-06-21 | Lynn Schick | Taste masking of essential oils using a hydrocolloid |
US20100323982A1 (en) * | 2007-06-27 | 2010-12-23 | N.V. Nutricia | Food composition for prodromal dementia patients |
US20100331275A1 (en) * | 2007-06-26 | 2010-12-30 | Martine Groenendijk | Supporting activities of daily living |
US20110009357A1 (en) * | 2007-06-26 | 2011-01-13 | N.V. Nutricia | Lipid composition for improving brain function |
US20110006917A1 (en) * | 2009-06-09 | 2011-01-13 | Denso Corporation | Parking aid system |
US20110027391A1 (en) * | 2007-12-20 | 2011-02-03 | N.V. Nutricia | Liquid nucleotides/nucleosides-containing product |
Family Cites Families (28)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU4595985A (en) | 1984-08-10 | 1986-02-13 | Sentrachem Limited | Cancer treatment |
US5470838A (en) | 1987-10-28 | 1995-11-28 | Pro-Neuron, Inc. | Method of delivering exogenous uridine or cytidine using acylated uridine or cytidine |
JPH0717855A (en) | 1992-09-02 | 1995-01-20 | Maruha Corp | Cerebral function-improving composition, learning ability-enhancing agent, mnemonic agent, dementia-preventing agent, dementia-treating agent, or functional food having cerebral function-improving effect |
JP3731983B2 (en) * | 1997-08-27 | 2006-01-05 | 明治製菓株式会社 | Drugs for improving night noise in dementia dogs |
GB9916536D0 (en) * | 1999-07-14 | 1999-09-15 | Scarista Limited | Nutritional or pharmaceutical compositions |
EP1090636A1 (en) | 1999-09-13 | 2001-04-11 | Société des Produits Nestlé S.A. | High lipid diet |
GB9925709D0 (en) | 1999-10-30 | 1999-12-29 | Smithkline Beecham Plc | Composition |
ES2752800T3 (en) | 2000-05-01 | 2020-04-06 | Cerecin Inc | Use of medium chain triglycerides for the treatment and prevention of Parkinson's disease resulting from reduced neuronal metabolism |
US7226916B1 (en) | 2000-05-08 | 2007-06-05 | N.V. Nutricia | Preparation for the prevention and/or treatment of vascular disorders |
SK287423B6 (en) | 2001-04-30 | 2010-09-07 | Trommsdorff Gmbh & Co. Kg Arzneimittel | Pharmaceutically active uridine esters, the use of them, method for the preparation of said uridine esters and pharmaceutical composition |
US6942874B2 (en) | 2001-05-25 | 2005-09-13 | Linguagen Corp. | Nucleotide compounds that block the bitter taste of oral compositions |
EP1285590A1 (en) | 2001-08-08 | 2003-02-26 | Société des Produits Nestlé S.A. | Lipid blends |
NL1019368C2 (en) * | 2001-11-14 | 2003-05-20 | Nutricia Nv | Preparation for improving receptor performance. |
SI1721612T1 (en) | 2003-10-24 | 2009-08-31 | Nutiricia Nv | Immunemodulating oligosaccharides |
JP2008513453A (en) * | 2004-09-15 | 2008-05-01 | マサチューセッツ インスティテュート オブ テクノロジー | Compositions containing uridine and methods of use thereof |
EP1656839A1 (en) | 2004-11-11 | 2006-05-17 | N.V. Nutricia | Nutrition containing lipid blend |
US20060252775A1 (en) | 2005-05-03 | 2006-11-09 | Henderson Samuel T | Methods for reducing levels of disease associated proteins |
AU2006251562B2 (en) * | 2005-05-23 | 2012-03-22 | Massachusetts Institute Of Technology | Compositions containing PUFA and methods of use thereof |
US20070135376A1 (en) | 2005-06-20 | 2007-06-14 | Accera, Inc. | Method to reduce oxidative damage and improve mitochondrial efficiency |
JP5697293B2 (en) | 2005-06-30 | 2015-04-08 | サントリーホールディングス株式会社 | Composition having an improving effect on lowering of higher brain function due to organic brain injury |
JP5967855B2 (en) | 2005-06-30 | 2016-08-10 | サントリーホールディングス株式会社 | Composition having an activity of reducing daytime activity and / or depressive symptoms |
ES2617577T3 (en) * | 2005-07-08 | 2017-06-19 | Dsm Ip Assets B.V. | Polyunsaturated fatty acids for the treatment of dementia and conditions related to pre-dementia |
WO2007058523A1 (en) * | 2005-11-17 | 2007-05-24 | N.V. Nutricia | Composition with docosapentaenoic acid |
ES2366034T3 (en) * | 2005-12-23 | 2011-10-14 | N.V. Nutricia | COMPOSITION THAT INCLUDES POLYINSATURATED FATTY ACIDS, PROTEINS, MANGANESE AND / OR MOLIBDENE AND NUCLEOSIDES / NUCLEOTIDES FOR THE TREATMENT OF DEMENTIA. |
CA2692309C (en) | 2007-06-26 | 2016-08-16 | N.V. Nutricia | Improving memory in subjects with mini-mental state examination of 24-26 |
WO2009057994A1 (en) | 2007-11-02 | 2009-05-07 | N.V. Nutricia | Unit dosage for brain health |
US8282335B2 (en) | 2009-06-12 | 2012-10-09 | Rs Drawings, Llc | Liftgate and mounting bracket system |
EP2456772A4 (en) | 2009-07-24 | 2013-02-27 | Amazentis Sa | Compounds, compositions and methods for protecting brain health in neurodegenerative disorders |
-
2008
- 2008-06-20 CA CA2692309A patent/CA2692309C/en active Active
- 2008-06-20 NZ NZ582329A patent/NZ582329A/en not_active IP Right Cessation
- 2008-06-20 PL PL08766834T patent/PL2170316T3/en unknown
- 2008-06-20 ES ES13189474T patent/ES2808406T3/en active Active
- 2008-06-20 EP EP13189474.3A patent/EP2689782B1/en active Active
- 2008-06-20 ES ES08766834.9T patent/ES2445401T3/en active Active
- 2008-06-20 PT PT87668349T patent/PT2170316E/en unknown
- 2008-06-20 AU AU2008269728A patent/AU2008269728B2/en active Active
- 2008-06-20 BR BRPI0813770A patent/BRPI0813770B1/en active IP Right Grant
- 2008-06-20 CN CN200880100603A patent/CN101765427A/en active Pending
- 2008-06-20 DK DK08766834.9T patent/DK2170316T3/en active
- 2008-06-20 RU RU2010102237/15A patent/RU2529815C2/en active
- 2008-06-20 MX MX2010000224A patent/MX2010000224A/en active IP Right Grant
- 2008-06-20 WO PCT/NL2008/050411 patent/WO2009002166A1/en active Application Filing
- 2008-06-20 NZ NZ599748A patent/NZ599748A/en unknown
- 2008-06-20 EP EP08766834.9A patent/EP2170316B1/en not_active Revoked
- 2008-06-20 US US12/666,611 patent/US20100331258A1/en not_active Abandoned
- 2008-06-20 CN CN201510144913.5A patent/CN104825480A/en active Pending
- 2008-06-20 JP JP2010514661A patent/JP5841723B2/en active Active
-
2014
- 2014-01-31 JP JP2014016605A patent/JP5934265B2/en active Active
- 2014-05-30 RU RU2014122168A patent/RU2677345C2/en active
-
2019
- 2019-11-26 US US16/696,941 patent/US11395810B2/en active Active
-
2022
- 2022-05-24 US US17/751,704 patent/US20220280466A1/en active Pending
Patent Citations (24)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3600197A (en) * | 1968-08-27 | 1971-08-17 | Merck & Co Inc | Flavor enhancing compositions for foods and beverages |
US5378488A (en) * | 1993-06-10 | 1995-01-03 | Abbott Laboratories | Aseptic processing of infant formula |
US5886037A (en) * | 1996-11-20 | 1999-03-23 | N.V. Nutricia | Nutritional composition for the treatment of hypertriglyceridaemia and hyperchylomicronaemia |
US20060241077A1 (en) * | 1998-07-31 | 2006-10-26 | Richard Wurtman | Methods and compositions for ameliorating or inhibiting decline in memory or intelligence or improving same |
US20070004670A1 (en) * | 1998-07-31 | 2007-01-04 | Richard Wurtman | Compositions containing citicoline, and methods of use thereof |
US6689467B1 (en) * | 1998-12-23 | 2004-02-10 | Rhodia Chimie | Composition comprising an inorganic coating and a core comprising at least a polyhydroxyl compound |
US6835750B1 (en) * | 2000-05-01 | 2004-12-28 | Accera, Inc. | Use of medium chain triglycerides for the treatment and prevention of alzheimer's disease and other diseases resulting from reduced neuronal metabolism II |
US20030114415A1 (en) * | 2001-12-14 | 2003-06-19 | Wurtman Richard J. | Compositions and methods for treating and preventing memory impairment using citicoline |
US20040001817A1 (en) * | 2002-05-14 | 2004-01-01 | Giampapa Vincent C. | Anti-aging nutritional supplement |
US20050208179A1 (en) * | 2004-03-18 | 2005-09-22 | Albrecht Daniel S | Nutritional formula containing select carotenoid combinations |
US7090879B2 (en) * | 2004-03-18 | 2006-08-15 | Abbott Laboratories | Nutritional formula containing select carotenoid combinations |
US20060025376A1 (en) * | 2004-05-13 | 2006-02-02 | Wurtman Richard J | Uridine effects on dopamine release |
US20070140992A1 (en) * | 2005-12-21 | 2007-06-21 | Lynn Schick | Taste masking of essential oils using a hydrocolloid |
US20100331275A1 (en) * | 2007-06-26 | 2010-12-30 | Martine Groenendijk | Supporting activities of daily living |
US20110009357A1 (en) * | 2007-06-26 | 2011-01-13 | N.V. Nutricia | Lipid composition for improving brain function |
US8283335B2 (en) * | 2007-06-26 | 2012-10-09 | N.V. Nutricia | Lipid composition for improving brain function |
US20130018012A1 (en) * | 2007-06-26 | 2013-01-17 | N.V. Nutricia | Lipid composition for improving brain function |
US8361989B2 (en) * | 2007-06-26 | 2013-01-29 | N. V. Nutricia | Supporting activities of daily living |
US20100323982A1 (en) * | 2007-06-27 | 2010-12-23 | N.V. Nutricia | Food composition for prodromal dementia patients |
US20110027391A1 (en) * | 2007-12-20 | 2011-02-03 | N.V. Nutricia | Liquid nucleotides/nucleosides-containing product |
US20110105594A1 (en) * | 2007-12-20 | 2011-05-05 | N.V. Nutricia | Palatable nutritional composition comprising a nucleotide and/or a nucleoside and a taste masking agent |
US8282965B2 (en) * | 2007-12-20 | 2012-10-09 | N.V. Nutricia | Liquid nucleotides/nucleosides-containing product |
US20130012469A1 (en) * | 2007-12-20 | 2013-01-10 | N.V. Nutricia | Liquid nucleotides/nucleosides-containing product |
US20110006917A1 (en) * | 2009-06-09 | 2011-01-13 | Denso Corporation | Parking aid system |
Non-Patent Citations (2)
Title |
---|
Purina Garden Recipe, http:// purinasmallanimals.com/SmallAnimals/Gerbil/PurinaGardenRecipeGerbiland... (retrieved 10/15/13) * |
Scheltens et al., Alzheimer's & Dementia (Jan. 2010) 1-10 * |
Cited By (17)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8361989B2 (en) | 2007-06-26 | 2013-01-29 | N. V. Nutricia | Supporting activities of daily living |
US20100331275A1 (en) * | 2007-06-26 | 2010-12-30 | Martine Groenendijk | Supporting activities of daily living |
US20110009357A1 (en) * | 2007-06-26 | 2011-01-13 | N.V. Nutricia | Lipid composition for improving brain function |
US11395810B2 (en) | 2007-06-26 | 2022-07-26 | N.V. Nutricia | Memory in subjects with mini-mental state examination of 24-26 |
US8791089B2 (en) | 2007-06-26 | 2014-07-29 | N.V. Nutricia | Supporting activities of daily living |
US8759319B2 (en) | 2007-06-26 | 2014-06-24 | N.V. Nutricia | Lipid composition for improving brain function |
US8283335B2 (en) | 2007-06-26 | 2012-10-09 | N.V. Nutricia | Lipid composition for improving brain function |
US8445458B2 (en) | 2007-06-27 | 2013-05-21 | N. V. Nutricia | Food composition for prodromal dementia patients |
US20100323982A1 (en) * | 2007-06-27 | 2010-12-23 | N.V. Nutricia | Food composition for prodromal dementia patients |
US8604000B2 (en) | 2007-12-20 | 2013-12-10 | N.V. Nutricia | Palatable nutritional composition comprising a nucleotide and/or a nucleoside and a taste masking agent |
US8282965B2 (en) | 2007-12-20 | 2012-10-09 | N.V. Nutricia | Liquid nucleotides/nucleosides-containing product |
US9132196B2 (en) | 2007-12-20 | 2015-09-15 | N. V. Nutricia | Palatable nutritional composition comprising a nucleotide and/or a nucleoside and a taste masking agent |
US9687555B2 (en) | 2007-12-20 | 2017-06-27 | N.V. Nutricia | Palatable nutritional composition comprising a nucleotide and/or a nucleoside and a taste masking agent |
US20110105594A1 (en) * | 2007-12-20 | 2011-05-05 | N.V. Nutricia | Palatable nutritional composition comprising a nucleotide and/or a nucleoside and a taste masking agent |
US20110158188A1 (en) * | 2008-02-01 | 2011-06-30 | Research In Motion Limited | System and Method for Uplink Timing Synchronization in Conjunction With Discontinuous Reception |
US20130331352A1 (en) * | 2010-12-28 | 2013-12-12 | N.V. Nutricia | Combination of Components for the Prevention and Treatment of Frailty |
US20150044138A1 (en) * | 2012-03-02 | 2015-02-12 | N.V. Nutricia | Method for improving functional synaptic connectivity |
Also Published As
Publication number | Publication date |
---|---|
MX2010000224A (en) | 2010-05-03 |
CA2692309C (en) | 2016-08-16 |
CA2692309A1 (en) | 2008-12-31 |
CN101765427A (en) | 2010-06-30 |
PL2170316T3 (en) | 2014-06-30 |
AU2008269728A1 (en) | 2008-12-31 |
ES2445401T3 (en) | 2014-03-03 |
BRPI0813770A8 (en) | 2017-06-06 |
RU2529815C2 (en) | 2014-09-27 |
AU2008269728B2 (en) | 2013-10-31 |
EP2170316B1 (en) | 2013-12-18 |
RU2010102237A (en) | 2011-08-10 |
BRPI0813770A2 (en) | 2014-12-30 |
US20200197345A1 (en) | 2020-06-25 |
JP2010531351A (en) | 2010-09-24 |
US11395810B2 (en) | 2022-07-26 |
WO2009002166A1 (en) | 2008-12-31 |
EP2170316A1 (en) | 2010-04-07 |
NZ582329A (en) | 2012-09-28 |
JP5841723B2 (en) | 2016-01-13 |
RU2014122168A (en) | 2015-12-10 |
BRPI0813770B1 (en) | 2018-05-08 |
NZ599748A (en) | 2013-11-29 |
ES2808406T3 (en) | 2021-02-26 |
CN104825480A (en) | 2015-08-12 |
US20220280466A1 (en) | 2022-09-08 |
EP2689782B1 (en) | 2020-05-13 |
JP2014074076A (en) | 2014-04-24 |
PT2170316E (en) | 2014-01-30 |
RU2677345C2 (en) | 2019-01-16 |
JP5934265B2 (en) | 2016-06-15 |
DK2170316T3 (en) | 2014-02-24 |
EP2689782A1 (en) | 2014-01-29 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US11395810B2 (en) | Memory in subjects with mini-mental state examination of 24-26 | |
US10071072B2 (en) | Method for treating neurotrauma | |
AU2016202656B2 (en) | Combination of components for the prevention and treatment of frailty | |
RU2637089C2 (en) | Method for control functions improvement | |
WO2009002148A1 (en) | Food composition for prodromal dementia patients | |
RU2705208C2 (en) | Method for assessing and treating or preventing disturbed levels of polar lipids in plasma | |
US9968629B2 (en) | Product and method for supporting uridine homeostasis | |
WO2015115885A1 (en) | Method for reducing white matter lesions, white matter hyperintensities (wmh), leukoaraiosis or periventricular white matter disease in elderly | |
WO2015160233A1 (en) | Method for assessing and treating or preventing impaired plasma polar lipid levels |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AS | Assignment |
Owner name: N.V. NUTRICIA, NETHERLANDS Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:KAMPHUIS, PATRICK JOSEPH GERARDUS HENDRIKUS;GROENENDIJK, MARTINE;BONGERS, ANKE;REEL/FRAME:024371/0046 Effective date: 20100112 |
|
STCV | Information on status: appeal procedure |
Free format text: ON APPEAL -- AWAITING DECISION BY THE BOARD OF APPEALS |
|
STCV | Information on status: appeal procedure |
Free format text: BOARD OF APPEALS DECISION RENDERED |
|
STCB | Information on status: application discontinuation |
Free format text: ABANDONED -- AFTER EXAMINER'S ANSWER OR BOARD OF APPEALS DECISION |