WO2011083827A1 - 脳神経細胞新生剤 - Google Patents
脳神経細胞新生剤 Download PDFInfo
- Publication number
- WO2011083827A1 WO2011083827A1 PCT/JP2011/050130 JP2011050130W WO2011083827A1 WO 2011083827 A1 WO2011083827 A1 WO 2011083827A1 JP 2011050130 W JP2011050130 W JP 2011050130W WO 2011083827 A1 WO2011083827 A1 WO 2011083827A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- plasmalogen
- agent
- cerebral
- item
- nerve cell
- Prior art date
Links
- 210000002569 neuron Anatomy 0.000 title claims abstract description 59
- 230000002490 cerebral effect Effects 0.000 title claims abstract description 51
- 230000009707 neogenesis Effects 0.000 title claims abstract description 18
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 claims abstract description 54
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 claims abstract description 28
- 229960001231 choline Drugs 0.000 claims abstract description 28
- 239000004480 active ingredient Substances 0.000 claims abstract description 19
- 241000271566 Aves Species 0.000 claims abstract description 15
- 230000002265 prevention Effects 0.000 claims abstract description 9
- 235000013305 food Nutrition 0.000 claims description 42
- 210000004556 brain Anatomy 0.000 claims description 41
- 239000003795 chemical substances by application Substances 0.000 claims description 41
- 208000012902 Nervous system disease Diseases 0.000 claims description 37
- 208000025966 Neurological disease Diseases 0.000 claims description 31
- 238000000034 method Methods 0.000 claims description 30
- 230000004766 neurogenesis Effects 0.000 claims description 19
- 206010003694 Atrophy Diseases 0.000 claims description 18
- 208000034189 Sclerosis Diseases 0.000 claims description 18
- 230000037444 atrophy Effects 0.000 claims description 18
- 230000034994 death Effects 0.000 claims description 18
- 230000009467 reduction Effects 0.000 claims description 17
- 239000000203 mixture Substances 0.000 claims description 14
- 230000001537 neural effect Effects 0.000 claims description 12
- 241000124008 Mammalia Species 0.000 claims description 11
- 210000004027 cell Anatomy 0.000 claims description 10
- 208000024827 Alzheimer disease Diseases 0.000 claims description 9
- 206010012289 Dementia Diseases 0.000 claims description 8
- 210000003792 cranial nerve Anatomy 0.000 claims description 8
- 201000000980 schizophrenia Diseases 0.000 claims description 8
- 206010028980 Neoplasm Diseases 0.000 claims description 7
- 230000009826 neoplastic cell growth Effects 0.000 claims description 7
- 230000001272 neurogenic effect Effects 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 2
- 230000000694 effects Effects 0.000 abstract description 13
- 239000000126 substance Substances 0.000 abstract description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 2
- 201000010099 disease Diseases 0.000 abstract 1
- 210000005036 nerve Anatomy 0.000 abstract 1
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 51
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 41
- 239000000284 extract Substances 0.000 description 25
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 14
- 239000000047 product Substances 0.000 description 14
- 108010013563 Lipoprotein Lipase Proteins 0.000 description 13
- 102100022119 Lipoprotein lipase Human genes 0.000 description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- 238000000605 extraction Methods 0.000 description 12
- 239000007788 liquid Substances 0.000 description 12
- 239000003960 organic solvent Substances 0.000 description 12
- 235000013330 chicken meat Nutrition 0.000 description 11
- 235000013372 meat Nutrition 0.000 description 11
- 239000002778 food additive Substances 0.000 description 10
- 235000013373 food additive Nutrition 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- -1 icosanyl group Chemical group 0.000 description 9
- 238000002360 preparation method Methods 0.000 description 9
- 101000720704 Homo sapiens Neuronal migration protein doublecortin Proteins 0.000 description 8
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
- 102100025929 Neuronal migration protein doublecortin Human genes 0.000 description 8
- 206010034203 Pectus Carinatum Diseases 0.000 description 8
- 238000005119 centrifugation Methods 0.000 description 8
- 150000002327 glycerophospholipids Chemical class 0.000 description 8
- 239000008177 pharmaceutical agent Substances 0.000 description 8
- 239000002244 precipitate Substances 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- 241000287828 Gallus gallus Species 0.000 description 7
- 235000013361 beverage Nutrition 0.000 description 7
- 239000000872 buffer Substances 0.000 description 7
- 238000007796 conventional method Methods 0.000 description 7
- 238000000105 evaporative light scattering detection Methods 0.000 description 7
- 230000001613 neoplastic effect Effects 0.000 description 7
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 210000001947 dentate gyrus Anatomy 0.000 description 6
- 239000008187 granular material Substances 0.000 description 6
- 238000006460 hydrolysis reaction Methods 0.000 description 6
- 150000002632 lipids Chemical class 0.000 description 6
- 102000004190 Enzymes Human genes 0.000 description 5
- 108090000790 Enzymes Proteins 0.000 description 5
- 239000000654 additive Substances 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- PEDCQBHIVMGVHV-UHFFFAOYSA-N glycerol group Chemical group OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 208000024891 symptom Diseases 0.000 description 5
- 241000894006 Bacteria Species 0.000 description 4
- 241000283707 Capra Species 0.000 description 4
- 241000699666 Mus <mouse, genus> Species 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 239000000969 carrier Substances 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 230000007062 hydrolysis Effects 0.000 description 4
- 238000012744 immunostaining Methods 0.000 description 4
- 239000012046 mixed solvent Substances 0.000 description 4
- 230000007935 neutral effect Effects 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 238000000638 solvent extraction Methods 0.000 description 4
- 241000283690 Bos taurus Species 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 101001092197 Homo sapiens RNA binding protein fox-1 homolog 3 Proteins 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 102100035530 RNA binding protein fox-1 homolog 3 Human genes 0.000 description 3
- 241000282887 Suidae Species 0.000 description 3
- 125000001931 aliphatic group Chemical group 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 3
- 235000013376 functional food Nutrition 0.000 description 3
- 230000036541 health Effects 0.000 description 3
- 235000013402 health food Nutrition 0.000 description 3
- 230000000971 hippocampal effect Effects 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 244000144972 livestock Species 0.000 description 3
- 235000012054 meals Nutrition 0.000 description 3
- 244000005700 microbiome Species 0.000 description 3
- 230000000474 nursing effect Effects 0.000 description 3
- 235000015097 nutrients Nutrition 0.000 description 3
- 239000002953 phosphate buffered saline Substances 0.000 description 3
- 150000003904 phospholipids Chemical class 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 230000001172 regenerating effect Effects 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 239000013589 supplement Substances 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- IKRZCYCTPYDXML-UHFFFAOYSA-N 2-hydroxypropane-1,2,3-tricarboxylic acid;hydrochloride Chemical compound Cl.OC(=O)CC(O)(C(O)=O)CC(O)=O IKRZCYCTPYDXML-UHFFFAOYSA-N 0.000 description 2
- 241000272525 Anas platyrhynchos Species 0.000 description 2
- 241000283086 Equidae Species 0.000 description 2
- 241000272184 Falconiformes Species 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- 208000018737 Parkinson disease Diseases 0.000 description 2
- 241001494479 Pecora Species 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 230000032683 aging Effects 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000001405 anti-neuronal effect Effects 0.000 description 2
- 230000003925 brain function Effects 0.000 description 2
- 235000009508 confectionery Nutrition 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- 230000037213 diet Effects 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 235000013355 food flavoring agent Nutrition 0.000 description 2
- 235000021588 free fatty acids Nutrition 0.000 description 2
- 210000001320 hippocampus Anatomy 0.000 description 2
- 230000003301 hydrolyzing effect Effects 0.000 description 2
- 238000007654 immersion Methods 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 206010027175 memory impairment Diseases 0.000 description 2
- 239000003147 molecular marker Substances 0.000 description 2
- 239000003068 molecular probe Substances 0.000 description 2
- 210000005155 neural progenitor cell Anatomy 0.000 description 2
- 235000016709 nutrition Nutrition 0.000 description 2
- 230000035764 nutrition Effects 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 235000021067 refined food Nutrition 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 235000019685 rice crackers Nutrition 0.000 description 2
- 235000015067 sauces Nutrition 0.000 description 2
- 235000014347 soups Nutrition 0.000 description 2
- 150000003408 sphingolipids Chemical class 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- 230000035882 stress Effects 0.000 description 2
- 229940126585 therapeutic drug Drugs 0.000 description 2
- CSVWWLUMXNHWSU-OYQPQXIVSA-N (3s,5s,8r,9s,10s,13r,14s,17r)-17-[(e,2r,5s)-5-ethyl-6-methylhept-3-en-2-yl]-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-3-ol Chemical compound C([C@@H]1CC2)[C@@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@H](C)/C=C/[C@@H](CC)C(C)C)[C@@]2(C)CC1 CSVWWLUMXNHWSU-OYQPQXIVSA-N 0.000 description 1
- RTHCYVBBDHJXIQ-MRXNPFEDSA-N (R)-fluoxetine Chemical compound O([C@H](CCNC)C=1C=CC=CC=1)C1=CC=C(C(F)(F)F)C=C1 RTHCYVBBDHJXIQ-MRXNPFEDSA-N 0.000 description 1
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 1
- 241000909284 Acidaminococcaceae Species 0.000 description 1
- 241000251468 Actinopterygii Species 0.000 description 1
- 239000012109 Alexa Fluor 568 Substances 0.000 description 1
- 235000002198 Annona diversifolia Nutrition 0.000 description 1
- 241000269350 Anura Species 0.000 description 1
- 240000006439 Aspergillus oryzae Species 0.000 description 1
- 235000002247 Aspergillus oryzae Nutrition 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- 241000282832 Camelidae Species 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 241000251730 Chondrichthyes Species 0.000 description 1
- 208000020401 Depressive disease Diseases 0.000 description 1
- 239000004278 EU approved seasoning Substances 0.000 description 1
- 241000283074 Equus asinus Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 1
- JZNWSCPGTDBMEW-UHFFFAOYSA-N Glycerophosphorylethanolamin Natural products NCCOP(O)(=O)OCC(O)CO JZNWSCPGTDBMEW-UHFFFAOYSA-N 0.000 description 1
- SQUHHTBVTRBESD-UHFFFAOYSA-N Hexa-Ac-myo-Inositol Natural products CC(=O)OC1C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C1OC(C)=O SQUHHTBVTRBESD-UHFFFAOYSA-N 0.000 description 1
- 241000282838 Lama Species 0.000 description 1
- 239000004909 Moisturizer Substances 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 229940123973 Oxygen scavenger Drugs 0.000 description 1
- 241000286209 Phasianidae Species 0.000 description 1
- 235000009827 Prunus armeniaca Nutrition 0.000 description 1
- 244000018633 Prunus armeniaca Species 0.000 description 1
- 241000669298 Pseudaulacaspis pentagona Species 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 230000001430 anti-depressive effect Effects 0.000 description 1
- 235000013527 bean curd Nutrition 0.000 description 1
- 230000003542 behavioural effect Effects 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 235000015895 biscuits Nutrition 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 235000008429 bread Nutrition 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 235000019219 chocolate Nutrition 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 235000014510 cooky Nutrition 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- 150000002009 diols Chemical class 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 235000015071 dressings Nutrition 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 125000005313 fatty acid group Chemical group 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 229960002464 fluoxetine Drugs 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 235000011194 food seasoning agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 1
- 210000004392 genitalia Anatomy 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 235000015220 hamburgers Nutrition 0.000 description 1
- 210000002216 heart Anatomy 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- CDAISMWEOUEBRE-GPIVLXJGSA-N inositol Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](O)[C@@H]1O CDAISMWEOUEBRE-GPIVLXJGSA-N 0.000 description 1
- 229960000367 inositol Drugs 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 235000015110 jellies Nutrition 0.000 description 1
- 239000008274 jelly Substances 0.000 description 1
- 235000008960 ketchup Nutrition 0.000 description 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000001333 moisturizer Effects 0.000 description 1
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 1
- 235000019575 mouthfulness Nutrition 0.000 description 1
- 125000001421 myristyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 210000002241 neurite Anatomy 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 230000016273 neuron death Effects 0.000 description 1
- 235000021590 normal diet Nutrition 0.000 description 1
- 125000000913 palmityl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000005325 percolation Methods 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 150000008104 phosphatidylethanolamines Chemical class 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 244000144977 poultry Species 0.000 description 1
- 235000013594 poultry meat Nutrition 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 235000020991 processed meat Nutrition 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 235000011962 puddings Nutrition 0.000 description 1
- 230000000384 rearing effect Effects 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- CDAISMWEOUEBRE-UHFFFAOYSA-N scyllo-inosotol Natural products OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 description 1
- 235000015170 shellfish Nutrition 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 235000013555 soy sauce Nutrition 0.000 description 1
- 235000013599 spices Nutrition 0.000 description 1
- 230000007480 spreading Effects 0.000 description 1
- 238000003892 spreading Methods 0.000 description 1
- 235000000891 standard diet Nutrition 0.000 description 1
- 125000004079 stearyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 210000001835 viscera Anatomy 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Images
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
- A61K31/66—Phosphorus compounds
- A61K31/683—Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols
- A61K31/685—Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols one of the hydroxy compounds having nitrogen atoms, e.g. phosphatidylserine, lecithin
-
- A—HUMAN NECESSITIES
- 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
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/56—Materials from animals other than mammals
- A61K35/57—Birds; Materials from birds, e.g. eggs, feathers, egg white, egg yolk or endothelium corneum gigeriae galli
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/12—Cyclic peptides, e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- 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
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- 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
- A61P25/24—Antidepressants
-
- 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
-
- 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
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
- A23V2200/322—Foods, ingredients or supplements having a functional effect on health having an effect on the health of the nervous system or on mental function
Definitions
- the present invention relates to a cerebral neurogenesis agent containing plasmalogen as an active ingredient, and more particularly to a cerebral neuronogenesis agent containing plasmalogen extracted from a living tissue as an active ingredient.
- Patent Document 1 describes that dictyosterol has an effect of promoting survival maintenance when nerve cells are damaged and sprouting and spreading of neurites, and is used for the treatment of neurological diseases. It has been suggested that it can be used.
- Patent Document 2 suggests that plasmalogen (phosphatidylethanolamine) has an inhibitory effect on neuronal cell death.
- Non-patent Document 1 Non-patent Document 1
- An object of the present invention is to provide a novel substance having a cerebro-neurogenesis effect.
- plasmalogen has an effect of cerebral nerve cell formation, and further improved and completed the present invention.
- mass% may be replaced with “weight%”.
- the present invention includes, for example, the subject matters described in the following sections.
- Item 1. A neurogenic agent for brain neuron containing plasmalogen as an active ingredient.
- Item 2-1 The cerebral nerve cell neogenesis agent of Claim 1 which contains the plasmalogen extracted from the biological tissue as an active ingredient.
- Item 2-2. Item 2.
- Item 3-1 The brain neuronogenesis agent according to claim 2, comprising plasmalogen extracted from avian tissue as an active ingredient.
- Item 3. The brain neuronogenesis agent according to Item 2-2, comprising a plasmalogen-containing avian tissue extract as an active ingredient.
- Item 4. The brain neuronal neoplasia according to any one of Items 1 to 3-2, wherein the plasmalogen contains an ethanolamine plasmalogen and a choline plasmalogen. Item 5. Item 5. The brain neuronal neoplasia according to Item 4, wherein 90% by mass or more of the plasmalogen is ethanolamine plasmalogen and choline plasmalogen. Item 6. Item 4 or wherein the plasmalogen contains ethanolamine plasmalogen and choline plasmalogen, and the mass ratio of (ethanolamine plasmalogen: choline plasmalogen) is (1: 5) to (1: 0.01). 5. The neurogenic agent for brain neurons according to 5. Item 7-1. Item 7.
- the agent for cerebral nerve cell neoplasia according to any one of Items 1 to 6, which is used for treatment and / or prevention of a neurological disease associated with sclerosis, atrophy, death, or reduction of cerebral nerve cells.
- Item 7-2. Item 7-1, wherein the neurological disorder involving sclerosis, atrophy, death, or reduction of brain neurons is at least one neurological disorder selected from the group consisting of Alzheimer's disease, depression, schizophrenia, and dementia.
- the neurogenic agent for brain neurons according to 1.
- Item 8-1 A composition comprising a plasmalogen and a pharmaceutically acceptable carrier or a food hygiene acceptable carrier.
- Item 8-2. A composition comprising a plasmalogen-containing avian tissue extract and a pharmaceutically acceptable or food hygiene acceptable carrier.
- a method of cerebral neurogenesis which comprises the step of taking an effective amount of plasmalogen in a subject.
- Item 9-2. A method for cerebral nerve cell neogenesis comprising a step of ingesting an effective amount of a plasmalogen-containing avian tissue extract into a subject.
- Item 9-3. A method for cerebral neuronogenesis comprising the step of ingesting an effective amount of the cerebral neuronogenesis agent according to any one of Items 1 to 7.
- Item 11-1. Item 11.
- the method for cerebral nerve cell neogenesis according to any one of Items 9-1 to 10, wherein the subject is a subject suffering from a neurological disease associated with sclerosis, atrophy, death, or reduction of brain neurons.
- Item 11-1 wherein the neurological disorder involving sclerosis, atrophy, death, or reduction of cranial nerve cells is at least one neurological disorder selected from the group consisting of Alzheimer's disease, depression, schizophrenia, and dementia.
- Item 12-1. A plasmalogen for use in the treatment or prevention of neurological diseases involving sclerosis, atrophy, death or reduction of brain neurons.
- Item 8. The brain neuronal neoplasia according to any one of Items 1 to 7 for use in the treatment or prevention of a neurological disease associated with sclerosis, atrophy, death, or reduction of brain neurons.
- Item 8. The composition according to Item 8-1 or 8-2, for use in the treatment or prevention of a neurological disease associated with sclerosis, atrophy, death, or reduction of cranial nerve cells.
- Item 12-1 is a neurological disease involving sclerosis, atrophy, death, or reduction of cranial nerve cells, which is at least one neurological disease selected from the group consisting of Alzheimer's disease, depression, schizophrenia, and dementia.
- Item 10. The plasmalogen described in Item 12, the plasmalogen-containing avian tissue extract described in Item 12-2, the cerebral neurogenesis agent described in Item 12-3, or the composition described in Item 12-4.
- Item 13-1 Use of a plasmalogen in the manufacture of a medicament for the treatment of a neurological disorder involving sclerosis, atrophy, death or reduction of brain neurons.
- Item 13-2 is a neurological disease involving sclerosis, atrophy, death, or reduction of cranial nerve cells, which is at least one neurological disease selected from the group consisting of Alzheimer's disease, depression, schizophrenia, and dementia.
- Item 13-3 Use of a plasmalogen-containing avian tissue extract in the manufacture of a medicament for the treatment of neurological diseases associated with sclerosis, atrophy, death or reduction of brain neurons.
- Item 13-3 The use according to Item 13-1 or 13-2, wherein the plasmalogen contains an ethanolamine plasmalogen and a choline plasmalogen.
- Item 13-4 The use according to Item 13-3, wherein 90% by mass or more of the plasmalogen is ethanolamine plasmalogen and choline plasmalogen.
- Item 13-5 The use according to Item 13-3, wherein 90% by mass or more of the plasmalogen is ethanolamine plasmalogen and choline plasmalogen.
- Item 13-3 wherein the plasmalogen contains ethanolamine plasmalogen and choline plasmalogen, and the mass ratio of (ethanolamine plasmalogen: choline plasmalogen) is (1: 5) to (1: 0) Use as described in 13-4.
- Item 13-1 is a neurological disease involving sclerosis, atrophy, death, or reduction of cranial nerve cells, which is at least one neurological disease selected from the group consisting of Alzheimer's disease, depression, schizophrenia, and dementia. The use according to any one of Items 13-5.
- Cerebral nerve cells (especially cerebral nerve cells of the dentate gyrus) can be renewed and increased by the cerebral nerve cell neoplastic agent of the present invention containing plasmalogen as an active ingredient. For this reason, it is considered that various neurological diseases can be treated with the cerebral nerve cell neoplastic agent. In particular, it has an excellent effect in the treatment and / or prevention of neurological diseases (for example, Alzheimer's disease, depression, schizophrenia, dementia, etc.) in which sclerosis, atrophy, death, or reduction of brain neurons can be observed. Conceivable.
- neurological diseases for example, Alzheimer's disease, depression, schizophrenia, dementia, etc.
- the cerebral nerve cell neogenesis agent of the present invention can particularly regenerate cerebral nerve cells of the dentate gyrus. Since the dentate gyrus is an area of the hippocampus that controls memory and is considered to play an important role in inputting information into the hippocampus, the neuronal neurogenesis agent of the present invention improves and treats memory impairment or learning It is thought that there is an effect of improving learning ability such as memory.
- plasmalogen is a component that is contained in a large amount of living tissue, when using a plasmalogen extracted from living tissue that has been conventionally edible The agent is considered to have very high safety with little concern about side effects.
- the chromatogram obtained by analyzing the high purity plasmalogen content extracted from the chicken breast meat by HPLC-ELSD is shown.
- plPE represents ethanolamine plasmalogen
- plPC represents choline plasmalogen.
- mouth of a plasmalogen administration group and a non-administration group is shown.
- the white scale bar described in the image indicates 50 ⁇ m.
- the present invention relates to a cerebral neurogenesis agent containing plasmalogen as an active ingredient.
- Plasmalogen usually refers to a glycerophospholipid having a long-chain alkenyl group via a vinyl ether bond at the 1-position of the glycerol skeleton.
- the general formula of plasmalogen is shown below.
- R 1 and R 2 represent an aliphatic hydrocarbon group.
- R 1 is usually an aliphatic hydrocarbon group having 1 to 20 carbon atoms, and examples thereof include a dodecyl group, a tetradecyl group, a hexadecyl group, an octadecyl group, and an icosanyl group.
- R 2 is usually an aliphatic hydrocarbon group derived from a fatty acid residue.
- octadecadienoyl group octadecatrienoyl group, icosatetraenoyl group, icosapentaenoyl group, docosatetraenoyl group, docosa Examples include a pentaenoyl group and a docosahexaenoyl group.
- X represents a polar group. X is preferably —CH 3 CH 3 NH 2 , —CH 3 CH 3 N + (CH 3 ) 3 , —CH 3 CH 2 (NH 2 ) COOH, or X is preferably X bound to H A group in which compound (H—X) is inositol or glycerol. ]
- an ethanolamine plasmalogen wherein X is an aminoethyl group (—CH 3 CH 3 NH 2 ) and a choline where X is a trimethylaminoethyl group (—CH 3 CH 3 N + (CH 3 ) 3 )
- Plasmalogens are the main plasmalogens that exist in nature.
- the plasmalogen contained in the cerebral nerve cell neoplastic of the present invention these two types are particularly preferable. That is, it is preferable that the cranial nerve cell neogenesis agent of this invention contains an ethanolamine plasmalogen and / or a choline plasmalogen as a plasmalogen.
- the plasmalogen used in the present invention is preferably extracted from a living tissue.
- the biological tissue here is a tissue containing plasmalogen in a living organism.
- organisms used for extracting plasmalogens include animals and microorganisms.
- An anaerobic bacterium is suitable as the microorganism, for example, an enteric bacterium of the family Acidaminococcaceae.
- living tissue is bacteria itself.
- animals, birds, mammals, fish, shellfish and the like are suitable.
- the mammal is preferably a livestock from the viewpoints of both supply stability and safety, and examples thereof include cattle, pigs, horses, sheep and goats.
- main tissues containing plasmalogens include skin, brain, intestine, heart, genital organs, and the like, and plasmalogens can be extracted from these tissues.
- birds include chickens, domestic duck, frogs, duck, eagle, eagle birds, turkeys and the like.
- chickens that have been used for food and are widely distributed in the market are particularly preferred.
- the bird tissue is not particularly limited, but it is preferable to use, for example, chicken meat (especially chicken breast meat), chicken skin, or internal organs of birds. Two or more different tissues of one or more kinds of organisms may be used in combination.
- a plasmalogen extracted from a bird tissue as a plasmalogen extracted from a living tissue.
- birds that have been conventionally used for food are suitable because they have been confirmed to be safe and can be stably supplied.
- the best is chicken.
- the method for extracting a plasmalogen from a living tissue is not particularly limited as long as the plasmalogen can be extracted (and purified if necessary).
- Conventionally known plasmalogen extraction methods can be appropriately selected.
- an extract extracted with water, an organic solvent, or a water-containing organic solvent can be used as a plasmalogen-containing biological tissue extract.
- the extraction and purification method includes the following steps (1) to (3).
- Extraction is preferably performed with water or an organic solvent (for example, at least one selected from the group consisting of methanol, ethanol, propanol, butanol, isopropanol, acetone, and hexane) or a water-containing organic solvent.
- the water content (v / v%) of the water-containing organic solvent is not particularly limited, and can be, for example, 10 to 90%. Of these, extraction with ethanol or hydrous ethanol is preferred.
- the bird tissue to be extracted may be raw or may have been subjected to some kind of processing in advance. For example, it may be bird tissue that has been previously dried and / or deoiled.
- Extraction treatment conditions are not particularly limited, but can be performed by an immersion method such as cold immersion or digestion, a percolation method, or the like.
- a preferred example is a method in which ethanol is added to chicken fillet and allowed to stand or stir at 30 ° C. or higher for 60 minutes or longer, preferably at 40 ° C. or higher for 180 minutes or longer.
- ethanol can be used, for example, in an amount of 1 to 10 L, preferably 1 to 6 L, more preferably 2 to 4 L with respect to 1 kg of dried chicken fillet.
- the obtained organic solvent extract is preferably subjected to a hydrolysis treatment step after being concentrated to dryness. Concentration to dryness can be performed according to a known method, for example, using an evaporator. In this way, an organic solvent extract (organic solvent extract dried product) is obtained.
- the organic solvent-extracted dried product contains a concentrated lipid such as plasmalogen.
- the organic solvent-extracted dried product is centrifuged, for example, with acetone, and then the precipitate is collected, and further, the liquid layer is collected after centrifugation with hexane / acetone mixed solvent.
- neutral lipid can be removed by collecting the precipitate after centrifugation with acetone
- sphingolipid can be removed by collecting the liquid layer after centrifugation with hexane / acetone mixed solvent. Can be done.
- the liquid layer thus obtained is concentrated and dried to obtain a phospholipid-concentrated dried product.
- the plasmalogen can be preferably concentrated by subjecting the phospholipid-concentrated dried product to a hydrolysis treatment step and hydrolyzing the diacyl phospholipid.
- PLA1 specifically hydrolyzes the bond between the sn-1 fatty acid and the glycerin skeleton in diacyl phospholipids.
- plasmalogen is not affected by PLA1 because sn-1 is an ether bond. Therefore, by treating with PLA1, diacyl glycerophospholipid is degraded, but plasmalogen is not degraded.
- diacyl glycerophospholipid is broken down into free fatty acids and lysophospholipids.
- Plasmalogen can be purified by converting diacyl-type glycerophospholipid coexisting with plasmalogen into a lyso form with PLA1 and removing free fatty acid and lysophospholipid.
- the origin of PLA1 is not particularly limited as long as the above effects can be obtained.
- An example is PLA1 derived from Aspergillus oryzae.
- Such PLA1 can be purchased from, for example, Mitsubishi Chemical Foods Corporation.
- the usage-amount can also be suitably set according to the amount of organic-solvent extraction dry solid to be used.
- 0.2 to 200 units / (organic solvent extracted dry product 1 mg) can be used, and more preferably 2 to 200 units / (organic solvent extracted dry product 1 mg) can be used.
- 1 unit means an amount (1 ⁇ mol / min) that changes 1 ⁇ mol of substrate (diacyl glycerophospholipid) per minute.
- the buffer used can be appropriately selected according to the PLA1 used.
- 0.1 M citrate-HCl buffer pH 4.5
- PLA1 may be added to the organic solvent-extracted dried product after the buffer is added and dissolved.
- the amount of buffer used is not particularly limited as long as the enzyme reaction can proceed, but is preferably 1 to 30 mL, more preferably about 5 to 15 mL per 1 g of the organic solvent-extracted dried product.
- reaction conditions can be set as appropriate, but the reaction is preferably carried out for 1 to 2 hours with stirring at 50 ° C.
- the enzyme may be deactivated after the hydrolysis reaction.
- the treatment is performed by raising the temperature to about 70 ° C. after the hydrolysis reaction.
- a treatment liquid in which the diacyl glycerophospholipid is decomposed can be obtained.
- the enzyme buffer and enzyme protein can be removed by adding, for example, 2 to 3 times the amount of hexane to the hydrolyzed solution and collecting the liquid layer (hexane layer) after centrifugation (the enzyme buffer and enzyme protein are water-soluble). Dissolved in the layer and not included in the hexane layer).
- plasmalogen dissolves in hexane but is hardly soluble in acetone, it is distributed by appropriately combining hexane, acetone and water, and further distributed in water or an aqueous solution (aqueous solution). Lipids can be removed to concentrate the plasmalogen. (Neutral lipids other than phospholipids can be removed with acetone, and plasmalogens and lysophospholipids can be separated by aqueous solution partitioning.)
- the biological tissue-extracted plasmalogen extracted and purified in this manner can be preferably used as an active ingredient of the cerebral nerve cell neogenesis agent of the present invention.
- a composition extracted from a biological tissue containing plasmalogen that is, a plasmalogen-containing biological tissue extract
- a plasmalogen-containing biological tissue extract can also be used as an active ingredient of the cerebral nerve cell neoplastic of the present invention.
- the biological tissue extraction plasmalogen mainly contains ethanolamine plasmalogen and / or choline plasmalogen.
- the mass ratio of ethanolamine plasmalogen and choline plasmalogen (ethanolamine plasmalogen: choline plasmalogen) in the biological tissue extraction plasmalogen may be (1: 5) to (1: 0).
- it is (1: 5) to (1: 0.01), more preferably (1: 5) to (5: 1), and (1: 3) to (3: 1).
- (1: 2) to (2: 1) is still more preferable
- (1: 1.5) to (1.5: 1) is still more preferable.
- a biological tissue-extracted plasmalogen containing choline plasmalogen can be preferably used for cerebral neuronogenesis.
- the biological tissue extraction plasmalogen used in the present invention preferably has a content of ethanolamine plasmalogen and choline plasmalogen of 50% by mass or more, more preferably 60% by mass or more, More preferable is 70% by mass or more, still more preferable is 80% by mass or more, and particularly preferable is 90% by mass or more.
- the mass ratio and content of ethanolamine plasmalogen and choline plasmalogen can be determined, for example, by analyzing a biological tissue-extracted plasmalogen by high performance liquid chromatography (HPLC). Specifically, in HPLC, a chromatogram is obtained by evaporative light scattering detection (ELSD) (ie, by HPLC-ELSD), and each peak indicating ethanolamine plasmalogen and choline plasmalogen in the chromatogram. The mass ratio can be obtained by obtaining the area ratio. Moreover, content can be calculated
- ELSD evaporative light scattering detection
- ELSD shows a similar area response if the substance has a similar structure.
- the choline type is electrically neutral, while ethanolamine has a negative charge of phosphoric acid and is weakly acidic.
- acetic acid and triethylamine are used as solvents to charge acidic lipids for analysis. Is preferred. This is because the same area response can be shown by charging.
- the amount of ethanolamine plasmalogen and choline plasmalogen can be quantified by analysis by LC-MS or the like, and the mass ratio and content can be obtained.
- the cerebral nerve cell neoplastic of the present invention is preferably used in the pharmaceutical field and food field.
- the agent contains a plasmalogen (preferably a biological tissue extraction plasmalogen).
- the agent may be composed solely of plasmalogen, or may be a composition containing plasmalogen and other components (such as various bases, carriers, and additives).
- the plasmalogen-containing biological tissue extract itself is also included in the composition. That is, a plasmalogen-containing biological tissue extract (and other ingredients blended as necessary) can also be used as the agent.
- the agent when used in the pharmaceutical field, the agent (hereinafter sometimes referred to as “the pharmaceutical agent according to the present invention”) may be composed only of plasmalogen, or other components may be used.
- a blended pharmaceutical composition may be used.
- plasmalogen which is an active ingredient
- a pharmaceutically acceptable base, carrier, additive for example, excipient, binder, disintegrant, lubricant
- additive for example, excipient, binder, disintegrant, lubricant
- Such base materials, carriers, additives and the like are specifically described in, for example, Pharmaceutical Additives Dictionary 2000 (Pharmaceutical Daily Inc.), and for example, those described therein can be used.
- the form of the preparation is not particularly limited, and the active ingredient and other ingredients are mixed by a conventional method. For example, tablets, coated tablets, powders, granules, fine granules, capsules, pills, liquids, suspensions, emulsions , Jelly preparations, chewable preparations, soft tablets and the like.
- tablets can be produced by a tableting method. Either a direct tableting method in which the mixed raw material is tableted as it is, or a granule tableting method in which the mixed raw material is granulated and then tableted can be used.
- the amount of plasmalogen blended in the pharmaceutical agent according to the present invention is not particularly limited as long as the cerebral neuronogenesis is exerted, and can be appropriately set according to the preferred daily plasmalogen intake.
- the amount is preferably 0.0005 to 100% by mass, more preferably 0.005 to 90% by mass, and still more preferably 0.05 to 80% by mass.
- the subject to which the pharmaceutical agent according to the present invention is administered is not limited, but is preferably a patient suffering from a neurological disease in which changes such as sclerosis, atrophy, death, or reduction of brain neurons are observed.
- a neurological disease in which changes such as sclerosis, atrophy, death, or reduction of brain neurons are observed.
- neurological diseases include dementia (Alzheimer's disease, Parkinson's disease, etc.), schizophrenia, depression and the like.
- the severity of the patient is not particularly limited, and can be preferably used for any of an early patient, a middle-term patient, and a late-stage patient.
- it can also be used prophylactically for people who are highly likely to suffer from such neurological diseases, such as the elderly.
- subjects to which the pharmaceutical agent according to the present invention is administered include not only humans but also non-human mammals. Mammals exhibiting the same symptoms as those described above can be exemplified, and mammals raised as pets and livestock are particularly preferable. Specific examples include dogs, cats, monkeys, cows, horses, sheep, goats, pigs, rabbits, mice, rats, camels, llamas, and the like. In the case of mammals, the pharmaceutical agent according to the present invention can be used prophylactically as in the case of humans.
- the administration time of the cerebral nerve cell neoplastic of the present invention is not particularly limited, and for example, the administration time can be appropriately selected in consideration of the preparation form, the age of the administration subject, the degree of symptoms of the administration subject, and the like.
- the administration form is not particularly limited, but oral administration is particularly suitable.
- the dosage of the cerebral neurogenesis agent of the present invention can be appropriately selected according to the age of the administration subject, the degree of symptoms of the administration subject, other conditions, and the like.
- the amount of plasmalogen in the agent is preferably 1 to 1000 mg per adult day, more preferably 10 to 100 mg.
- the administration can be performed once or a plurality of times (preferably 2 to 3 times) a day. In the case of mammals, the dose can be appropriately set with reference to the case of the person concerned.
- the agent when used as a food additive for cerebral nerve cell neogenesis, the agent (hereinafter sometimes referred to as “food additive according to the present invention”) may be plasmalogen itself.
- a composition for food addition in which ingredients and materials that can be used as food additives, as well as bases, carriers, and additives that are acceptable in food hygiene, may be used.
- food additives include, but are not limited to, liquids, powders, flakes, granules, and pastes. Specific examples include seasonings (soy sauce, sauce, ketchup, dressing, etc.), flakes (sprinkles), grilled meat sauce, spices, roux paste (carrille paste, etc.) and the like.
- Such food additives can be appropriately prepared according to conventional methods.
- the amount of plasmalogen blended in the food additive according to the present invention is not particularly limited as long as cerebral neurogenesis is exhibited, but is preferably 0.0005 to 100% by mass, more preferably 0.005 to 90% by mass, More preferably, it is 0.05 to 80% by mass.
- Such a food additive according to the present invention is ingested by eating a food to which the food additive is added.
- the said addition may be performed during food preparation or manufacture, and may be performed immediately before eating cooked food or while eating.
- the food additive is taken orally in this manner, it exerts a neurogenic effect on brain neurons.
- the intake of the food additive which concerns on this invention, the subject of intake, the measurement of the amount of contained plasmalogen etc. are not restrict
- the agent (hereinafter sometimes referred to as “the food / beverage product according to the present invention”) is acceptable in terms of plasmalogen and food hygiene.
- Bases, carriers, additives, and other components and materials that can be used as food and drink For example, processed foods, beverages, health foods (nutrient functional foods, foods for specified health use, etc.), supplements, foods for sick people (hospital foods) for plasma neurogens, for cerebral neurogenesis or for improving or preventing symptoms of neurological diseases Food composition such as sick food or nursing food).
- the plasmalogen blended with the agent is a biological tissue-extracted plasmalogen extracted from the tissue of livestock or poultry (eg, cattle, pigs, chickens, etc.), for example, the plasmalogen is blended.
- Processed meat foods such as hamburger, meatballs, wieners, chicken socks, chicken skin chips, and health foods (nutrient functional foods, foods for specified health use, etc.), supplements, foods for the sick Etc.
- the plasmalogen is powdered, beverages (juice etc.), confectionery (eg gum, chocolate, candy, biscuits, cookies, rice crackers, rice crackers, pudding, apricot tofu etc.), breads, soup It may be contained in various foods and beverages such as foods (including powdered soups) and processed foods.
- the present invention when preparing foods and drinks according to the present invention as health foods (nutrient functional foods, foods for specified health use, etc.) and supplements, for example, granules, capsules, tablets (chewable preparations) so as to facilitate continuous intake Etc.), preferably in the form of beverages (drinks), among which the capsule, tablet, and tablet are preferred from the viewpoint of ease of ingestion, but are not particularly limited thereto.
- the neuronal neurogenesis agent comprising the food and drink according to the present invention in the form of granules, capsules, tablets and the like should be appropriately prepared according to a conventional method using a pharmaceutically and / or food hygienically acceptable carrier. Can do. Moreover, even if it is a case where it prepares in another form, what is necessary is just to follow the conventional method.
- the blending amount of plasmalogen in the food and drink according to the present invention is not particularly limited as long as it can exert the cerebral neuronogenesis effect, but is preferably 0.0005 to 100% by mass, more preferably 0.005 to 90% by mass, and further Preferably, it is 0.05 to 80% by mass.
- the food and drink according to the present invention can be preferably used for improving or preventing symptoms of neurological diseases.
- the intake amount, the intake target, the measurement of the contained plasmalogen amount, and the like are not particularly limited, but are preferably the same as, for example, the pharmaceutical agent according to the present invention described above.
- the hospital food is a meal served when hospitalized, the sick food is a meal for the sick, and the care food is a meal for the care recipient.
- the food / beverage products according to the present invention can be preferably used as hospital foods, sick foods or nursing foods for patients who are hospitalized due to neurological diseases, home medical treatment, etc., or patients who are receiving nursing care. It can also be taken prophylactically by people who are highly likely to suffer from neurological diseases, such as the elderly.
- the present invention relates to a method for preventing or improving a neurological disease characterized by orally administering or ingesting the brain neuronal neoplastic agent of the present invention to a neurological disease patient, a human or a mammal who is highly likely to suffer from the neurological disease, etc. And methods of treatment are also provided. Specifically, this method is carried out by administering or ingesting the above-mentioned cerebral neurogenesis agent of the present invention. In this method, the conditions such as the subject, administration route or intake amount are as described above.
- Preparation Example 1 Manufacture of tissue- derived plasmalogen-containing fraction
- Chicken breast meat which is a bird tissue, is collected in accordance with a conventional method, chopped into minced meat of about 8 mm, subjected to a heating process for microorganism control, and then chilled. Stored frozen. Then, freeze-drying was performed by a conventional method and pulverized by a grinder treatment. The dried breast meat powder was stored sealed with an oxygen scavenger until used for extraction.
- Step (3) 20 g of the plasmalogen-containing fraction obtained as described above was dispersed in 400 mL of a phospholipase A1 (Mitsubishi Chemical Foods) solution (10 mg / mL, 0.1 M citric acid-HCl buffer), and 2% at 50 ° C. under nitrogen gas filling. Stir for hours. Thereafter, the mixture was cooled, and twice the volume of hexane was added, and the mixture was stirred and distributed twice. Furthermore, the operation of adding 60 mL of acetone to the dried solid, stirring and centrifuging, and collecting the precipitate was repeated twice.
- a phospholipase A1 Mitsubishi Chemical Foods
- the plasmalogen obtained from chicken fillet was found to be a mixture of ethanolamine plasmalogen (plPE) and choline plasmalogen (plPC).
- plPE ethanolamine plasmalogen
- plPC choline plasmalogen
- the area ratio of plasmalogen was 94.6%
- the former was 47.9%
- the latter was 46.7%. Therefore, it was found that the chicken breast meat-derived high-purity plasmalogen-containing product obtained contained 94.6% by mass of plasmalogen.
- the peak position of the plasmalogen can be known, for example, by analyzing the standard in advance.
- the chicken breast meat-derived high-purity plasmalogen-containing material was used as a bird tissue extraction plasmalogen.
- Example 1 Examination of the effect of biological tissue-extracted plasmalogen on brain neurons To examine the effect of avian tissue-extracted plasmalogen on brain neurons, the following experiment was conducted.
- AIN-93M a standard diet for mouse and rat nutrition research published in 1993 by the National Institute of Nutrition
- normal diet a mouse diet used for experiments
- AIN-93M containing 0.1% by mass of a bird tissue-extracted plasmalogen (hereinafter sometimes referred to as “0.1% pl-containing feed”) was also purchased by special order (both Oriental Yeast Co., Ltd.) ).
- SAMP8 Senescence-Accelerated Mouse-Prone 8
- the administration group was bred with a diet containing 0.1% pl ad libitum for 25 weeks.
- the non-administration group the normal feed was freely fed for 25 weeks and reared. During breeding, water was freely consumed. After the rearing, perfusion fixation was performed on 2 administration groups and 2 non-administration groups, and frozen sections were prepared according to a conventional method.
- immunostaining was performed as follows. 20 ⁇ m brain sections were treated with blocking solution for 30 minutes at room temperature, then reacted with appropriately diluted primary antibodies (DCX (1: 500), NeuN (1: 1000)) and allowed to stand at 4 ° C. overnight. did. Then, after washing several times with PBS (phosphate buffered saline), the secondary antibody was appropriately diluted (1: 500), allowed to react, allowed to stand at room temperature for 6 hours, washed several times with PBS, and then brain Section specimens were prepared. The specimens were observed and analyzed with a confocal microscope.
- the antibodies used are as follows.
- anti-neuronal nuclear antibody Anti-Neuronal Nuclei (NeuN) monoclomal antibody, derived from Millipore
- fluorescent labeled anti-mouse IgG antibody Labeled Anti-Mouse IgG antibody
- Alexa Fluor 568 derived from shark goat, manufactured by Molecular Probes
- doublecortin antibody (DCX; Doublecortin (N-19): sc-8067, derived from goat, manufactured by SantatechnologyCruz ⁇ Biotechnology) is used as the primary antibody, and fluorescence-labeled anti-goat IgG antibody (as a secondary antibody) ( Labeled Anti-Goat IgG antibody, derived from donkey, manufactured by Molecular Probes) was used.
- the immunostaining method can be said to be the most common and highly reliable experimental method in the present situation where research on neurogenesis is actively conducted and evaluation methods and experimental techniques are improving day by day.
- the immunostaining method is a method of visualizing an antigen-antibody reaction that is originally invisible, and is one of the most frequently used methods for evaluating neurogenesis.
- the molecular marker for neural progenitor cells used here Doublecortin (DCX), is a molecular marker frequently used in many papers and can be said to be one of the most reliable molecular markers. Therefore, it can be said that the experimental results obtained this time are also highly reliable.
- FIG. 2 is the image which observed the hippocampal dentate gyrus.
- DCX doublecortin®
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Mycology (AREA)
- Food Science & Technology (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Psychiatry (AREA)
- Gastroenterology & Hepatology (AREA)
- Polymers & Plastics (AREA)
- Nutrition Science (AREA)
- Hospice & Palliative Care (AREA)
- Pain & Pain Management (AREA)
- Psychology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
Abstract
Description
項1.
プラズマローゲンを有効成分として含む脳神経細胞新生剤。
項2-1.
生体組織から抽出されたプラズマローゲンを有効成分として含む請求項1に記載の脳神経細胞新生剤。
項2-2.
プラズマローゲン含有生体組織抽出物を有効成分として含む項1に記載の脳神経細胞新生剤。
項3-1.
鳥組織から抽出されたプラズマローゲンを有効成分として含む請求項2-1に記載の脳神経細胞新生剤。
項3-2.
プラズマローゲン含有鳥組織抽出物を有効成分として含む項2-2に記載の脳神経細胞新生剤。
項4.
前記プラズマローゲンにエタノールアミンプラズマローゲン及びコリンプラズマローゲンが含有される、項1~3-2のいずれかに記載の脳神経細胞新生剤。
項5.
前記プラズマローゲンの90質量%以上がエタノールアミンプラズマローゲン及びコリンプラズマローゲンである、項4に記載の脳神経細胞新生剤。
項6.
前記プラズマローゲンが、エタノールアミンプラズマローゲン及びコリンプラズマローゲンを含有し、(エタノールアミンプラズマローゲン:コリンプラズマローゲン)の質量比が(1:5)~(1:0.01)である、項4又は5に記載の脳神経細胞新生剤。
項7-1.
脳神経細胞の硬化、萎縮、死滅、又は減少を伴う神経疾患の治療及び/又は予防用である、項1~6のいずれかに記載の脳神経細胞新生剤。
項7-2.
脳神経細胞の硬化、萎縮、死滅、又は減少を伴う神経疾患が、アルツハイマー病、うつ病、統合失調症、及び認知症からなる群より選択される少なくとも1種の神経疾患である、項7-1に記載の脳神経細胞新生剤。
項8-1.
プラズマローゲン、及び薬学的に許容される担体又は食品衛生学上許容される担体を含む、組成物。
項8-2.
プラズマローゲン含有鳥組織抽出物、及び薬学的に許容される担体又は食品衛生学上許容される担体を含む、組成物。
項9-1.
プラズマローゲンを対象に有効量摂取させる工程を含む、脳神経細胞新生方法。
項9-2.
プラズマローゲン含有鳥組織抽出物を対象に有効量摂取させる工程を含む、脳神経細胞新生方法。
項9-3.
項1~7のいずれかに記載の脳神経細胞新生剤を対象に有効量摂取させる工程を含む、脳神経細胞新生方法。
項10.
前記対象が、ヒトを含む哺乳動物である、項9-1~9-3のいずれかに記載の脳神経細胞新生方法。
項11-1.
前記対象が、脳神経細胞の硬化、萎縮、死滅、又は減少を伴う神経疾患を患った対象である、項9-1~10のいずれかに記載の脳神経細胞新生方法。
項11-2.
脳神経細胞の硬化、萎縮、死滅、又は減少を伴う神経疾患が、アルツハイマー病、うつ病、統合失調症、及び認知症からなる群より選択される少なくとも1種の神経疾患である、項11-1に記載の脳神経細胞新生方法。
項12-1.
脳神経細胞の硬化、萎縮、死滅、又は減少を伴う神経疾患の治療又は予防における使用のためのプラズマローゲン。
項12-2.
脳神経細胞の硬化、萎縮、死滅、又は減少を伴う神経疾患の治療又は予防における使用のためのプラズマローゲン含有鳥組織抽出物。
項12-3.
脳神経細胞の硬化、萎縮、死滅、又は減少を伴う神経疾患の治療又は予防における使用のための項1~7のいずれかに記載の脳神経細胞新生剤。
項12-4.
脳神経細胞の硬化、萎縮、死滅、又は減少を伴う神経疾患の治療又は予防における使用のための項8-1又は8-2に記載の組成物。
項12-5.
脳神経細胞の硬化、萎縮、死滅、又は減少を伴う神経疾患が、アルツハイマー病、うつ病、統合失調症、及び認知症からなる群より選択される少なくとも1種の神経疾患である、項12-1に記載のプラズマローゲン、項12-2に記載のプラズマローゲン含有鳥組織抽出物、項12-3に記載の脳神経細胞新生剤、又は項12-4に記載の組成物。
項13-1.
脳神経細胞の硬化、萎縮、死滅、又は減少を伴う神経疾患の治療のための医薬の製造におけるプラズマローゲンの使用。
項13-2.
脳神経細胞の硬化、萎縮、死滅、又は減少を伴う神経疾患の治療のための医薬の製造におけるプラズマローゲン含有鳥組織抽出物の使用。
項13-3.
前記プラズマローゲンにエタノールアミンプラズマローゲン及びコリンプラズマローゲンが含有される、項13-1又は13-2に記載の使用。
項13-4.
前記プラズマローゲンの90質量%以上がエタノールアミンプラズマローゲン及びコリンプラズマローゲンである、項13-3に記載の使用。
項13-5.
前記プラズマローゲンが、エタノールアミンプラズマローゲン及びコリンプラズマローゲンを含有し、(エタノールアミンプラズマローゲン:コリンプラズマローゲン)の質量比が(1:5)~(1:0)である、項13-3又は13-4に記載の使用。
項13-6.
脳神経細胞の硬化、萎縮、死滅、又は減少を伴う神経疾患が、アルツハイマー病、うつ病、統合失調症、及び認知症からなる群より選択される少なくとも1種の神経疾患である、項13-1~項13-5のいずれかに記載の使用。
(1)生体組織抽出物から中性脂質及びスフィンゴ脂質を除去する工程
(2)工程(1)を経た前記抽出物を加水分解処理する工程
(3)工程(2)を経た前記抽出物からジアシル型グリセロリン脂質分解物を除去する工程
この抽出及び精製方法によれば、ジアシル型グリセロリン脂質を分解・除去できるため、プラズマローゲンの純度をより一層高めることができ、この点でも好ましい。このようにして得られる抽出物は、プラズマローゲン含有生体組織抽出物として好ましく用い得る。なお、以下“生体組織から抽出されたプラズマローゲン”を“生体組織抽出プラズマローゲン”と記載することがある。また、例えば“鳥組織から抽出されたプラズマローゲン”を“鳥組織抽出プラズマローゲン”と記載することがある。
鳥組織である鶏ムネ肉を常法に従って採取し、約8mmのミンチへチョッピングし、微生物制御のために加熱工程を経た後、これをチルド冷凍保存した。その後、常法により凍結乾燥を行い、グラインダー処理により粉砕した。乾燥胸肉粉末は、抽出に使用するまで脱酸素剤と共に密封保存した。
工程(1)
上述のようにして得た乾燥ムネ肉粉末1kgにエタノール4Lを加えて12時間、40℃で撹拌・静置し、その後抽出液を固形物と分離した。固形物には再度エタノール2.5Lを加えて前述のとおり抽出し、得られた抽出液を合わせて濾紙で濾過後、減圧乾燥して濃縮された抽出乾固物を得た。
工程(2)
上述の抽出乾固物に水8mLを加えて撹拌、遠心し、上層を除去した。この沈殿にアセトン200mLを加えて撹拌、4℃で遠心し、アセトン層を除去した。さらにこの沈殿にアセトン100mLを加えて撹拌、遠心し、沈殿を回収した。さらにこの沈殿にヘキサン/アセトン(7:3)混合溶媒100mLを加えて撹拌、遠心し、液層(プラズマローゲン含有画分)20gを回収した。液層は速やかにロータリーエバポレーターで濃縮乾固した。なお、遠心は3000rpm×10minで行い、アセトン単一及びヘキサン/アセトン混合溶媒を用いたものは4℃、他は15℃で行なった。
工程(3)
上述のようにして得たプラズマローゲン含有画分20gを、ホスホリパーゼA1(三菱化学フーズ)溶液400mL(10mg/mL 0.1Mクエン酸-HClバッファー)中に分散させ、窒素ガス充填下で50℃で2時間撹拌した。その後、冷却し、2倍容量のヘキサンを加えて2回撹拌、分配し、上層を回収して濃縮乾固した。さらに、当該乾固物にアセトンを60mL加えて撹拌、遠心し、沈殿を回収する操作を2回繰り返した。さらに当該沈殿にヘキサン/アセトン(7:3) 60mL加えて撹拌、遠心し、液層(高純度プラズマローゲン含有画分)を回収した。この液層に、ヘキサン198mLとアセトン222mL(すなわち、合計でヘキサン/アセトン(1:1)となる)を加えて分液ロートに移し、水を72mL添加して撹拌・分配した。下層(アセトン層)を除去し、上層(ヘキサン層)にアセトン/水(5:3)192mLを添加して、撹拌・分配した。上層(ヘキサン層)を回収し、速やかに減圧乾燥して鶏ムネ肉由来高純度プラズマローゲン含有物を得た。
上述のようにして得た鶏ムネ肉由来高純度プラズマローゲン含有物を下記条件のHPLCにて解析し、クロマトグラムを得た。
[HPLC解析条件]
機器;Shimadzu LC-10AD
カラム;LiChrospher Diol 100(250-4, Merck社)(プレカラム無し)
溶媒;A液:ヘキサン/2-プロパノール/酢酸(82:17:1. v/v),B液:2-プロパノール/水/酢酸(85:14:1, v/v)+0.2%トリエチルアミン
グラジエント条件:
鳥組織抽出プラズマローゲンが脳神経細胞に及ぼす影響を検討するため、以下の実験を行った。
実験に使用するマウスの飼料として、AIN-93M(米国国立栄養研究所により1993年に発表されたマウス・ラットの栄養研究用標準飼料)を購入した(以下「通常飼料」と表記することがある)。また、特別注文により、鳥組織抽出プラズマローゲンを0.1質量%含有するAIN-93M(以下「0.1%pl含有飼料」と表記することがある)も購入した(いずれもオリエンタル酵母株式会社)。
老化促進マウスSenescence-Accelerated Mouse-Prone 8 (SAMP8)14匹を、日本エスエルシー株式会社から購入し、プラズマローゲン投与群(n=7)及び非投与群(n=7)に群分けした。SAMP8は、学習・記憶障害をはじめとする行動生理学的障害、免疫応答能低下を示すモデルマウスである。投与群には、0.1%pl含有飼料を25週間自由摂取させて飼育した。非投与群には、通常飼料を25週間自由摂取させて飼育した。なお、飼育中、水は自由摂取とした。飼育後、投与群2匹及び非投与群2匹について、灌流固定を行い、凍結切片を常法に従って作成し、これを免疫染色して比較検討した。
Claims (13)
- プラズマローゲンを有効成分とする脳神経細胞新生剤。
- 生体組織から抽出されたプラズマローゲンを有効成分とする請求項1に記載の脳神経細胞新生剤。
- 鳥組織から抽出されたプラズマローゲンを有効成分とする請求項2に記載の脳神経細胞新生剤。
- 前記プラズマローゲンにエタノールアミンプラズマローゲン及びコリンプラズマローゲンが含有される、請求項1~3のいずれかに記載の脳神経細胞新生剤。
- 前記プラズマローゲンの90質量%以上がエタノールアミンプラズマローゲン及びコリンプラズマローゲンである、請求項4に記載の脳神経細胞新生剤。
- 前記プラズマローゲンが、エタノールアミンプラズマローゲン及びコリンプラズマローゲンを含有し、(エタノールアミンプラズマローゲン:コリンプラズマローゲン)の質量比が(1:5)~(1:0.01)である、請求項4又は5に記載の脳神経細胞新生剤。
- アルツハイマー病、うつ病、統合失調症、及び認知症からなる群より選択される少なくとも1種の神経疾患の治療及び/又は予防用である、請求項1~6のいずれかに記載の脳神経細胞新生剤。
- プラズマローゲン、及び薬学的に許容される担体又は食品衛生学上許容される担体を含む、組成物。
- プラズマローゲンを対象に有効量摂取させる工程を含む、脳神経細胞新生方法。
- 前記対象が、ヒトを含む哺乳動物である、請求項9に記載の脳神経細胞新生方法。
- 前記対象が、脳神経細胞の硬化、萎縮、死滅、又は減少を伴う神経疾患を患った対象である、請求項9又は10に記載の脳神経細胞新生方法。
- 脳神経細胞の硬化、萎縮、死滅、又は減少を伴う神経疾患の治療又は予防における使用のためのプラズマローゲン。
- 脳神経細胞の硬化、萎縮、死滅、又は減少を伴う神経疾患の治療のための医薬の製造におけるプラズマローゲンの使用。
Priority Applications (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP11731825.3A EP2522353A4 (en) | 2010-01-06 | 2011-01-06 | Active substance for brain nerve cell genesis |
US13/520,899 US8822437B2 (en) | 2010-01-06 | 2011-01-06 | Cerebral nerve cell neogenesis agent |
CN2011800053234A CN102711770A (zh) | 2010-01-06 | 2011-01-06 | 脑神经细胞新生剂 |
JP2011549025A JP6016363B2 (ja) | 2010-01-06 | 2011-01-06 | 脳神経細胞新生剤 |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2010-001337 | 2010-01-06 | ||
JP2010001337 | 2010-01-06 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2011083827A1 true WO2011083827A1 (ja) | 2011-07-14 |
Family
ID=44305564
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/JP2011/050130 WO2011083827A1 (ja) | 2010-01-06 | 2011-01-06 | 脳神経細胞新生剤 |
Country Status (6)
Country | Link |
---|---|
US (1) | US8822437B2 (ja) |
EP (1) | EP2522353A4 (ja) |
JP (1) | JP6016363B2 (ja) |
KR (1) | KR20120114335A (ja) |
CN (1) | CN102711770A (ja) |
WO (1) | WO2011083827A1 (ja) |
Cited By (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2012090625A1 (ja) * | 2010-12-28 | 2012-07-05 | 医療法人社団ブックス | 認知症を血液サンプルで判定するための検査方法 |
EP2522353A1 (en) * | 2010-01-06 | 2012-11-14 | Marudai Food Co., Ltd. | Cerebral nerve cell neogenesis agent |
EP2620154A1 (en) * | 2010-09-24 | 2013-07-31 | Fujino Brain Research Co., Ltd. | Drug against central nervous system inflammation |
JP2016210696A (ja) * | 2015-04-30 | 2016-12-15 | 丸大食品株式会社 | 学習記憶能力増強剤 |
WO2017191838A1 (ja) * | 2016-05-02 | 2017-11-09 | 有限会社梅田事務所 | 安全・安定なプラズマローゲンとその製剤及び認知症の未病状態の判定方法 |
JP2018104663A (ja) * | 2016-05-02 | 2018-07-05 | 有限会社梅田事務所 | 安全・安定なプラズマローゲンとその製剤及び認知症の未病状態の判定方法 |
JP2019142818A (ja) * | 2018-02-21 | 2019-08-29 | 丸大食品株式会社 | リン脂質濃縮物生産方法 |
WO2019208392A1 (ja) * | 2018-04-27 | 2019-10-31 | 株式会社レオロジー機能食品研究所 | 新規プラズマローゲン誘導体 |
JP2019199482A (ja) * | 2019-08-20 | 2019-11-21 | 丸大食品株式会社 | 学習記憶能力増強剤 |
US10653708B2 (en) | 2017-06-16 | 2020-05-19 | Institute of Rheological Functions of Food | Uses of ether phospholipids in treating diseases |
KR20200130276A (ko) | 2018-03-08 | 2020-11-18 | 니혼 야쿠힌 가부시키가이샤 | 플라스말로겐을 함유하는 조성물을 제조하는 방법 |
US11066432B2 (en) | 2014-12-08 | 2021-07-20 | Institute of Rheological Functions of Food | Ether phospholipids and method for producing the same |
US11142537B2 (en) | 2018-02-21 | 2021-10-12 | Marudai Food Co., Ltd. | Phospholipid concentrate manufacturing method |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPWO2020040291A1 (ja) * | 2018-08-24 | 2021-10-07 | 日本薬品株式会社 | 記憶能力を増強するための、プラズマローゲンを含有する組成物 |
Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH10505614A (ja) * | 1995-07-07 | 1998-06-02 | エスアーエールエル アンスティチュ ディジエン エ ディエテティク | ホスホグリセロエーテルをベースとした新規組成物と、神経変性疾患の治療におけるその利用 |
JP2003003190A (ja) * | 2001-06-25 | 2003-01-08 | Yaizu Suisankagaku Industry Co Ltd | 高度不飽和脂肪酸供給組成物 |
JP2003012520A (ja) * | 2001-06-25 | 2003-01-15 | Yaizu Suisankagaku Industry Co Ltd | 抗酸化剤及びそれを含有する飲食品 |
JP2004026803A (ja) * | 2002-03-29 | 2004-01-29 | Nof Corp | 神経細胞死予防剤 |
JP2007262024A (ja) * | 2006-03-29 | 2007-10-11 | Tohoku Univ | プラズマローゲン含有脂質の抽出方法及びプラズマローゲン含有脂質、並びに機能性飲食品 |
WO2008093709A1 (ja) * | 2007-01-30 | 2008-08-07 | Tohoku University | アミロイド蛋白質の凝集抑制および分解促進によりアミロイドーシスと関連する疾患を予防または治療するための組成物 |
WO2008146942A1 (ja) * | 2007-05-28 | 2008-12-04 | Umeda Jimusho Ltd. | リン脂質含有機能性素材の製造方法およびプラズマローゲン型グリセロリン脂質の製造方法 |
Family Cites Families (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4687783A (en) | 1983-03-01 | 1987-08-18 | Hoerrmann Wilhelm | Fatty aldehydes and acids in the treatment of neurological and dermatological diseases |
JP2001031572A (ja) | 1999-07-22 | 2001-02-06 | Kyorin Pharmaceut Co Ltd | ジクチオステロールを有効成分とする中枢神経細胞突起再生薬 |
US7033612B2 (en) * | 2003-01-03 | 2006-04-25 | Kang David S | Composition and method for treating age-related disorders |
EP2127536A4 (en) | 2007-02-21 | 2010-12-22 | Umeda Jimusho Ltd | METHOD FOR PRODUCING A FUNCTIONAL MATERIAL, FUNCTIONAL MATERIAL AND DEVICE FOR CONTINUOUS HEATING TO OBTAIN |
EP2308954B1 (en) | 2008-06-20 | 2012-10-24 | Umeda Jimusho Ltd. | Method for production of highly pure phospholipid, and highly pure sphingomyelin and plasmalogen-type glycerophospholipid produced by the method |
EP2522353A4 (en) * | 2010-01-06 | 2013-06-19 | Marudai Food Co Ltd | Active substance for brain nerve cell genesis |
CN103118685B (zh) | 2010-09-24 | 2015-09-30 | 藤野脑研究株式会社 | 抗中枢神经系统炎症的药物 |
-
2011
- 2011-01-06 EP EP11731825.3A patent/EP2522353A4/en not_active Withdrawn
- 2011-01-06 CN CN2011800053234A patent/CN102711770A/zh active Pending
- 2011-01-06 JP JP2011549025A patent/JP6016363B2/ja active Active
- 2011-01-06 WO PCT/JP2011/050130 patent/WO2011083827A1/ja active Application Filing
- 2011-01-06 US US13/520,899 patent/US8822437B2/en active Active
- 2011-01-06 KR KR1020127020645A patent/KR20120114335A/ko not_active Application Discontinuation
Patent Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH10505614A (ja) * | 1995-07-07 | 1998-06-02 | エスアーエールエル アンスティチュ ディジエン エ ディエテティク | ホスホグリセロエーテルをベースとした新規組成物と、神経変性疾患の治療におけるその利用 |
JP2003003190A (ja) * | 2001-06-25 | 2003-01-08 | Yaizu Suisankagaku Industry Co Ltd | 高度不飽和脂肪酸供給組成物 |
JP2003012520A (ja) * | 2001-06-25 | 2003-01-15 | Yaizu Suisankagaku Industry Co Ltd | 抗酸化剤及びそれを含有する飲食品 |
JP2004026803A (ja) * | 2002-03-29 | 2004-01-29 | Nof Corp | 神経細胞死予防剤 |
JP2007262024A (ja) * | 2006-03-29 | 2007-10-11 | Tohoku Univ | プラズマローゲン含有脂質の抽出方法及びプラズマローゲン含有脂質、並びに機能性飲食品 |
WO2008093709A1 (ja) * | 2007-01-30 | 2008-08-07 | Tohoku University | アミロイド蛋白質の凝集抑制および分解促進によりアミロイドーシスと関連する疾患を予防または治療するための組成物 |
WO2008146942A1 (ja) * | 2007-05-28 | 2008-12-04 | Umeda Jimusho Ltd. | リン脂質含有機能性素材の製造方法およびプラズマローゲン型グリセロリン脂質の製造方法 |
Non-Patent Citations (2)
Title |
---|
See also references of EP2522353A4 * |
TERUO MIYAZAWA: "Functional foods for supporting smart aging in human", JOURNAL OF JAPANESE SOCIETY FOR INTEGRATIVE MEDICINE, vol. 1, no. 1, 2008, pages 84 - 90 * |
Cited By (22)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP2522353A1 (en) * | 2010-01-06 | 2012-11-14 | Marudai Food Co., Ltd. | Cerebral nerve cell neogenesis agent |
EP2620154A1 (en) * | 2010-09-24 | 2013-07-31 | Fujino Brain Research Co., Ltd. | Drug against central nervous system inflammation |
EP2620154A4 (en) * | 2010-09-24 | 2014-02-19 | Fujino Brain Res Co Ltd | MEDICAMENT AGAINST IGNITION OF THE CENTRAL NERVOUS SYSTEM |
JP5847086B2 (ja) * | 2010-09-24 | 2016-01-20 | 株式会社藤野ブレインリサーチ | 抗中枢神経系炎症剤 |
WO2012090625A1 (ja) * | 2010-12-28 | 2012-07-05 | 医療法人社団ブックス | 認知症を血液サンプルで判定するための検査方法 |
US11066432B2 (en) | 2014-12-08 | 2021-07-20 | Institute of Rheological Functions of Food | Ether phospholipids and method for producing the same |
JP2016210696A (ja) * | 2015-04-30 | 2016-12-15 | 丸大食品株式会社 | 学習記憶能力増強剤 |
WO2017191838A1 (ja) * | 2016-05-02 | 2017-11-09 | 有限会社梅田事務所 | 安全・安定なプラズマローゲンとその製剤及び認知症の未病状態の判定方法 |
CN109153693A (zh) * | 2016-05-02 | 2019-01-04 | 有限会社梅田事务所 | 安全-稳定的缩醛磷脂和其制剂及认知症的未病状态的判断方法 |
CN109153693B (zh) * | 2016-05-02 | 2022-08-02 | 有限会社梅田事务所 | 安全-稳定的缩醛磷脂和其制剂及认知症的未病状态的判断方法 |
JP2018104663A (ja) * | 2016-05-02 | 2018-07-05 | 有限会社梅田事務所 | 安全・安定なプラズマローゲンとその製剤及び認知症の未病状態の判定方法 |
JP7016093B2 (ja) | 2016-05-02 | 2022-02-04 | 有限会社梅田事務所 | 安全・安定なプラズマローゲンとその製剤及び認知症の未病状態の判定方法 |
US10653708B2 (en) | 2017-06-16 | 2020-05-19 | Institute of Rheological Functions of Food | Uses of ether phospholipids in treating diseases |
WO2019163856A1 (ja) * | 2018-02-21 | 2019-08-29 | 丸大食品株式会社 | リン脂質濃縮物生産方法 |
US11091720B2 (en) | 2018-02-21 | 2021-08-17 | Marudai Food Co., Ltd. | Method for producing phospholipid concentrate |
US11142537B2 (en) | 2018-02-21 | 2021-10-12 | Marudai Food Co., Ltd. | Phospholipid concentrate manufacturing method |
JP2019142818A (ja) * | 2018-02-21 | 2019-08-29 | 丸大食品株式会社 | リン脂質濃縮物生産方法 |
KR20200130276A (ko) | 2018-03-08 | 2020-11-18 | 니혼 야쿠힌 가부시키가이샤 | 플라스말로겐을 함유하는 조성물을 제조하는 방법 |
US11517594B2 (en) | 2018-03-08 | 2022-12-06 | Nihon Pharmaceutical Co., Ltd. | Methods for producing compositions containing plasmalogen |
JP6664638B1 (ja) * | 2018-04-27 | 2020-03-13 | 株式会社 レオロジー機能食品研究所 | 新規プラズマローゲン誘導体 |
WO2019208392A1 (ja) * | 2018-04-27 | 2019-10-31 | 株式会社レオロジー機能食品研究所 | 新規プラズマローゲン誘導体 |
JP2019199482A (ja) * | 2019-08-20 | 2019-11-21 | 丸大食品株式会社 | 学習記憶能力増強剤 |
Also Published As
Publication number | Publication date |
---|---|
US8822437B2 (en) | 2014-09-02 |
EP2522353A1 (en) | 2012-11-14 |
JP6016363B2 (ja) | 2016-10-26 |
EP2522353A4 (en) | 2013-06-19 |
US20120283223A1 (en) | 2012-11-08 |
CN102711770A (zh) | 2012-10-03 |
JPWO2011083827A1 (ja) | 2013-05-16 |
KR20120114335A (ko) | 2012-10-16 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6016363B2 (ja) | 脳神経細胞新生剤 | |
JP5847086B2 (ja) | 抗中枢神経系炎症剤 | |
JP6207545B2 (ja) | 学習記憶能力増強剤 | |
JP2021508343A (ja) | リゾホスファチジルコリン組成物 | |
WO2016092878A1 (ja) | エーテルリン脂質およびその製造方法 | |
JP6603923B2 (ja) | 認知機能の改善作用を有する鶏胸肉由来プラズマローゲン組成物及びこれを含有して成る認知機能の向上及び/又は改善用食品組成物又はサプリメント | |
WO2017191838A1 (ja) | 安全・安定なプラズマローゲンとその製剤及び認知症の未病状態の判定方法 | |
WO2014184655A1 (en) | Methods for using crustacean phospholipid-peptide-protein complexes | |
EP3725320B1 (en) | Composition comprising agathobaculum sp. strain as effective ingredient for prevention, alleviation, or treatment of autism spectrum disorder | |
CN109153693B (zh) | 安全-稳定的缩醛磷脂和其制剂及认知症的未病状态的判断方法 | |
JP5689055B2 (ja) | 鳥皮由来スフィンゴミエリン含有物を有効成分とする抗高血糖及び/又は抗高脂血症剤 | |
JP6842093B2 (ja) | 学習記憶能力増強剤 | |
WO2011083853A1 (ja) | 抗アトピー性皮膚炎剤 | |
JP2017165785A (ja) | 学習記憶能力増強剤 | |
JP2009102226A (ja) | 脊髄損傷治療剤 | |
JP6399920B2 (ja) | 体脂肪低減剤、体重減少促進剤、血中中性脂肪低減剤及び血中遊離脂肪酸低減剤 | |
JP2023119096A (ja) | 間葉系細胞活性化剤、創傷治療剤、間葉系細胞活性化用経口組成物及び創傷治療用経口組成物 | |
CN111801109A (zh) | 能够改善认知功能的肽 | |
JP2006232725A (ja) | 食品または医薬組成物 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
WWE | Wipo information: entry into national phase |
Ref document number: 201180005323.4 Country of ref document: CN |
|
121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 11731825 Country of ref document: EP Kind code of ref document: A1 |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2011549025 Country of ref document: JP |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
WWE | Wipo information: entry into national phase |
Ref document number: 13520899 Country of ref document: US |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2011731825 Country of ref document: EP |
|
ENP | Entry into the national phase |
Ref document number: 20127020645 Country of ref document: KR Kind code of ref document: A |