JP5264269B2 - Sex hormone inducer and protein metabolism improvement and constitution improvement method using the same - Google Patents
Sex hormone inducer and protein metabolism improvement and constitution improvement method using the same Download PDFInfo
- Publication number
- JP5264269B2 JP5264269B2 JP2008116644A JP2008116644A JP5264269B2 JP 5264269 B2 JP5264269 B2 JP 5264269B2 JP 2008116644 A JP2008116644 A JP 2008116644A JP 2008116644 A JP2008116644 A JP 2008116644A JP 5264269 B2 JP5264269 B2 JP 5264269B2
- Authority
- JP
- Japan
- Prior art keywords
- oleuropein
- protein
- testosterone
- hormones
- constitution
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 239000000411 inducer Substances 0.000 title claims description 5
- 239000003163 gonadal steroid hormone Substances 0.000 title description 13
- 230000022558 protein metabolic process Effects 0.000 title description 10
- 238000000034 method Methods 0.000 title description 5
- 230000006872 improvement Effects 0.000 title description 4
- MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 claims description 38
- RFWGABANNQMHMZ-HYYSZPHDSA-N Oleuropein Chemical compound O([C@@H]1OC=C([C@H](C1=CC)CC(=O)OCCC=1C=C(O)C(O)=CC=1)C(=O)OC)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O RFWGABANNQMHMZ-HYYSZPHDSA-N 0.000 claims description 27
- RFWGABANNQMHMZ-UHFFFAOYSA-N 8-acetoxy-7-acetyl-6,7,7a,8-tetrahydro-5H-benzo[g][1,3]dioxolo[4',5':4,5]benzo[1,2,3-de]quinoline Natural products CC=C1C(CC(=O)OCCC=2C=C(O)C(O)=CC=2)C(C(=O)OC)=COC1OC1OC(CO)C(O)C(O)C1O RFWGABANNQMHMZ-UHFFFAOYSA-N 0.000 claims description 21
- HKVGJQVJNQRJPO-UHFFFAOYSA-N Demethyloleuropein Natural products O1C=C(C(O)=O)C(CC(=O)OCCC=2C=C(O)C(O)=CC=2)C(=CC)C1OC1OC(CO)C(O)C(O)C1O HKVGJQVJNQRJPO-UHFFFAOYSA-N 0.000 claims description 21
- 235000011576 oleuropein Nutrition 0.000 claims description 21
- RFWGABANNQMHMZ-CARRXEGNSA-N oleuropein Natural products COC(=O)C1=CO[C@@H](O[C@H]2O[C@@H](CO)[C@H](O)[C@@H](O)[C@@H]2O)C(=CC)[C@H]1CC(=O)OCCc3ccc(O)c(O)c3 RFWGABANNQMHMZ-CARRXEGNSA-N 0.000 claims description 21
- 229960003604 testosterone Drugs 0.000 claims description 19
- BIWKXNFEOZXNLX-BBHIFXBUSA-N oleuropein aglycone Chemical compound COC(=O)C1=CO[C@@H](O)\C(=C\C)[C@@H]1CC(=O)OCCC1=CC=C(O)C(O)=C1 BIWKXNFEOZXNLX-BBHIFXBUSA-N 0.000 claims description 16
- DEBZOPZQKONWTK-KWCYVHTRSA-N oleuropein aglycone Natural products COC(=O)C1=CO[C@H](C)[C@@H](C=O)[C@@H]1CC(=O)OCCc1ccc(O)c(O)c1 DEBZOPZQKONWTK-KWCYVHTRSA-N 0.000 claims description 14
- 239000004480 active ingredient Substances 0.000 claims description 8
- 229940088597 hormone Drugs 0.000 description 20
- 239000005556 hormone Substances 0.000 description 20
- 230000028327 secretion Effects 0.000 description 15
- 235000005911 diet Nutrition 0.000 description 12
- 230000037213 diet Effects 0.000 description 12
- 235000013305 food Nutrition 0.000 description 10
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- JUUBCHWRXWPFFH-UHFFFAOYSA-N Hydroxytyrosol Chemical compound OCCC1=CC=C(O)C(O)=C1 JUUBCHWRXWPFFH-UHFFFAOYSA-N 0.000 description 8
- 235000018102 proteins Nutrition 0.000 description 8
- 102000004169 proteins and genes Human genes 0.000 description 8
- 108090000623 proteins and genes Proteins 0.000 description 8
- FIKLMMHLPVXWJN-WRWORJQWSA-N Elenolic acid Chemical compound COC(=O)C1=CO[C@@H](O)C(=CC)[C@@H]1CC(O)=O FIKLMMHLPVXWJN-WRWORJQWSA-N 0.000 description 7
- 240000007817 Olea europaea Species 0.000 description 7
- 230000009471 action Effects 0.000 description 6
- 230000001195 anabolic effect Effects 0.000 description 6
- 239000005018 casein Substances 0.000 description 6
- 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 6
- 235000021240 caseins Nutrition 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 102000009151 Luteinizing Hormone Human genes 0.000 description 5
- 108010073521 Luteinizing Hormone Proteins 0.000 description 5
- 230000036541 health Effects 0.000 description 5
- 230000001939 inductive effect Effects 0.000 description 5
- 229940040129 luteinizing hormone Drugs 0.000 description 5
- OMFXVFTZEKFJBZ-UHFFFAOYSA-N Corticosterone Natural products O=C1CCC2(C)C3C(O)CC(C)(C(CC4)C(=O)CO)C4C3CCC2=C1 OMFXVFTZEKFJBZ-UHFFFAOYSA-N 0.000 description 4
- 108010051696 Growth Hormone Proteins 0.000 description 4
- 102000018997 Growth Hormone Human genes 0.000 description 4
- 239000003098 androgen Substances 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 230000015556 catabolic process Effects 0.000 description 4
- OMFXVFTZEKFJBZ-HJTSIMOOSA-N corticosterone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@H](CC4)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OMFXVFTZEKFJBZ-HJTSIMOOSA-N 0.000 description 4
- 230000037406 food intake Effects 0.000 description 4
- 239000000122 growth hormone Substances 0.000 description 4
- 235000003248 hydroxytyrosol Nutrition 0.000 description 4
- 229940095066 hydroxytyrosol Drugs 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 210000001550 testis Anatomy 0.000 description 4
- TWCMVXMQHSVIOJ-UHFFFAOYSA-N Aglycone of yadanzioside D Natural products COC(=O)C12OCC34C(CC5C(=CC(O)C(O)C5(C)C3C(O)C1O)C)OC(=O)C(OC(=O)C)C24 TWCMVXMQHSVIOJ-UHFFFAOYSA-N 0.000 description 3
- PLMKQQMDOMTZGG-UHFFFAOYSA-N Astrantiagenin E-methylester Natural products CC12CCC(O)C(C)(CO)C1CCC1(C)C2CC=C2C3CC(C)(C)CCC3(C(=O)OC)CCC21C PLMKQQMDOMTZGG-UHFFFAOYSA-N 0.000 description 3
- 108700012941 GNRH1 Proteins 0.000 description 3
- 239000000579 Gonadotropin-Releasing Hormone Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- PFOARMALXZGCHY-UHFFFAOYSA-N homoegonol Natural products C1=C(OC)C(OC)=CC=C1C1=CC2=CC(CCCO)=CC(OC)=C2O1 PFOARMALXZGCHY-UHFFFAOYSA-N 0.000 description 3
- 235000008390 olive oil Nutrition 0.000 description 3
- 239000004006 olive oil Substances 0.000 description 3
- 230000001737 promoting effect Effects 0.000 description 3
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- 230000014616 translation Effects 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- DATAGRPVKZEWHA-YFKPBYRVSA-N N(5)-ethyl-L-glutamine Chemical compound CCNC(=O)CC[C@H]([NH3+])C([O-])=O DATAGRPVKZEWHA-YFKPBYRVSA-N 0.000 description 2
- UCTWMZQNUQWSLP-UHFFFAOYSA-N adrenaline Chemical compound CNCC(O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-UHFFFAOYSA-N 0.000 description 2
- 229940030486 androgens Drugs 0.000 description 2
- 235000013361 beverage Nutrition 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 235000013399 edible fruits Nutrition 0.000 description 2
- 239000003623 enhancer Substances 0.000 description 2
- 229940011871 estrogen Drugs 0.000 description 2
- 239000000262 estrogen Substances 0.000 description 2
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 2
- 239000003862 glucocorticoid Substances 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 235000013402 health food Nutrition 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 230000037356 lipid metabolism Effects 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- 210000001672 ovary Anatomy 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 230000003248 secreting effect Effects 0.000 description 2
- 235000003687 soy isoflavones Nutrition 0.000 description 2
- OGNSCSPNOLGXSM-UHFFFAOYSA-N (+/-)-DABA Natural products NCCC(N)C(O)=O OGNSCSPNOLGXSM-UHFFFAOYSA-N 0.000 description 1
- 208000014644 Brain disease Diseases 0.000 description 1
- ZNZYKNKBJPZETN-WELNAUFTSA-N Dialdehyde 11678 Chemical compound N1C2=CC=CC=C2C2=C1[C@H](C[C@H](/C(=C/O)C(=O)OC)[C@@H](C=C)C=O)NCC2 ZNZYKNKBJPZETN-WELNAUFTSA-N 0.000 description 1
- 206010013786 Dry skin Diseases 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 241000402754 Erythranthe moschata Species 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 102000051325 Glucagon Human genes 0.000 description 1
- 108060003199 Glucagon Proteins 0.000 description 1
- 102000004366 Glucosidases Human genes 0.000 description 1
- 108010056771 Glucosidases Proteins 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- 206010062767 Hypophysitis Diseases 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 1
- 102100037852 Insulin-like growth factor I Human genes 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 102000014171 Milk Proteins Human genes 0.000 description 1
- 108010011756 Milk Proteins Proteins 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 108010073771 Soybean Proteins Proteins 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 210000004404 adrenal cortex Anatomy 0.000 description 1
- 210000004100 adrenal gland Anatomy 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 230000001925 catabolic effect Effects 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000037336 dry skin Effects 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- 230000008713 feedback mechanism Effects 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- MASNOZXLGMXCHN-ZLPAWPGGSA-N glucagon Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 MASNOZXLGMXCHN-ZLPAWPGGSA-N 0.000 description 1
- 229960004666 glucagon Drugs 0.000 description 1
- 229930182470 glycoside Natural products 0.000 description 1
- 150000002338 glycosides Chemical class 0.000 description 1
- 210000002149 gonad Anatomy 0.000 description 1
- 230000003054 hormonal effect Effects 0.000 description 1
- 210000003016 hypothalamus Anatomy 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- CJWQYWQDLBZGPD-UHFFFAOYSA-N isoflavone Natural products C1=C(OC)C(OC)=CC(OC)=C1C1=COC2=C(C=CC(C)(C)O3)C3=C(OC)C=C2C1=O CJWQYWQDLBZGPD-UHFFFAOYSA-N 0.000 description 1
- 150000002515 isoflavone derivatives Chemical class 0.000 description 1
- 235000008696 isoflavones Nutrition 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000014972 male genitalia development Effects 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 230000009245 menopause Effects 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- 230000007102 metabolic function Effects 0.000 description 1
- 235000021239 milk protein Nutrition 0.000 description 1
- 230000037257 muscle growth Effects 0.000 description 1
- 235000021590 normal diet Nutrition 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000001151 other effect Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 210000003635 pituitary gland Anatomy 0.000 description 1
- 210000002826 placenta Anatomy 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 238000001243 protein synthesis Methods 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 208000020016 psychiatric disease Diseases 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000018406 regulation of metabolic process Effects 0.000 description 1
- 230000001850 reproductive effect Effects 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 230000009645 skeletal growth Effects 0.000 description 1
- 235000019710 soybean protein Nutrition 0.000 description 1
- 239000003270 steroid hormone Substances 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000005728 strengthening Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 229940037128 systemic glucocorticoids Drugs 0.000 description 1
- 229940026510 theanine Drugs 0.000 description 1
- 210000001685 thyroid gland Anatomy 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
Images
Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
- Non-Alcoholic Beverages (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
本発明は性ホルモン誘発機能を有する医薬品および飲食品組成物に関するものである。また、性ホルモン誘発機能を中心とした作用によるタンパク代謝改善、体質改善方法の提供に関するものである。 The present invention relates to a pharmaceutical product having a sex hormone-inducing function and a food or beverage composition. The present invention also relates to the provision of a method for improving protein metabolism and constitution by an action centered on a sex hormone-inducing function.
ホルモンは内分泌性の物質で、様々なかたちで体内の代謝調節に関与し健康維持に役立っている。例えば、成長ホルモンは肝臓、腎臓などに働きかけてキーとなる成分の分泌促進を通して骨を成長させ、また体内細胞に蓄積された成分の放出・分解などを通して、成長に必要なタンパク質の合成、筋肉の形成を促す働きをする。また、性ホルモンは二次性徴等身体の生殖機能の発育に大きく影響し、男性は男性らしい身体の、女性は女性らしい身体の形成に関与する。これらホルモンは関連する他のホルモンの分泌促進、或いは分泌抑制の機能を有するなど、お互いに影響を及ぼすものも多い。 Hormones are endocrine substances that are involved in regulating metabolism in the body in various ways and help maintain health. For example, growth hormone works on the liver, kidneys, etc. to promote the secretion of key components, grows bone, and releases and decomposes components accumulated in body cells to synthesize proteins necessary for growth, muscle It works to encourage formation. Sex hormones greatly influence the development of the body's reproductive functions, such as secondary sexual characteristics, and men are involved in the formation of masculine bodies and women in feminine bodies. Many of these hormones affect each other, for example, have the function of promoting secretion or inhibiting secretion of other related hormones.
健康維持に必須なホルモンは常にそのバランスが重要となり、適度なバランスが維持されていないと健康を害し、さらには疾病に至る場合もある。一方、老齢化や疾病、不摂生によってくずれたホルモンバランスを元に戻すには食品に含まれる特定の成分の摂取が有効であることがある。さらには、これら特定の成分の摂取により、ある種のホルモンの分泌作用が増強され健康増進、体力増強など個々の生活にプラスとなる効果が得られる場合もある。 The balance of hormones essential for maintaining health is always important, and if an appropriate balance is not maintained, health may be harmed and even diseases may be caused. On the other hand, in order to restore the hormonal balance that has been lost due to aging, illness, or ingestion, it may be effective to ingest certain components contained in food. Furthermore, ingestion of these specific components may enhance the secretory action of certain hormones, and may have positive effects on individual lives such as health promotion and physical strength enhancement.
これまでに、乳タンパク質の加水分解物を有効成分とする消化管ホルモン分泌促進剤（特許文献１）、γアミノ酪酸を有効成分とする成長ホルモン分泌促進剤（特許文献２）、大豆蛋白を酵素分解して得られる特定の分子量を持つペプチド混合物を有効成分とする成長ホルモン分泌促進剤（特許文献３）、アンブレッド・シード油または大環状ムスクを有効成分とする女性ホルモン分泌促進剤（特許文献４）、テアニンを有効成分とする副腎皮質刺激ホルモン分泌促進剤（特許文献５）等が提案されている。他にも、大豆に含まれるイソフラボンは、体内で女性ホルモンであるエストロゲンに似た働きをすることから、大豆イソフラボンを有効成分とする閉経後のホルモンバランスの崩れに起因する脂性乾燥肌を予防する食品（特許文献６）が提案されており、さらには、大豆イソフラボンは継続的な摂取により更年期に発生する障害の緩和やある種のがんの予防に役立つといわれている。 So far, digestive tract hormone secretion promoter (Patent Document 1) containing hydrolyzate of milk protein as an active ingredient, growth hormone secretion promoter (Patent Document 2) containing γ-aminobutyric acid as an active ingredient, soybean protein as an enzyme Growth hormone secretion enhancer comprising a peptide mixture having a specific molecular weight obtained by decomposition as an active ingredient (Patent Document 3), female hormone secretion enhancer comprising ambread seed oil or macrocyclic musk as an active ingredient (Patent Document) 4) Adrenal cortex stimulating hormone secretion promoter (Patent Document 5) and the like containing theanine as an active ingredient have been proposed. In addition, isoflavones contained in soybeans act like female hormones, estrogen, in the body, thus preventing oily dry skin caused by disruption of postmenopausal hormone balance with soy isoflavones as active ingredients. Food (Patent Document 6) has been proposed, and soy isoflavone is said to be useful for alleviating disorders that occur during menopause and preventing certain types of cancer by continuous ingestion.
本発明品であるオレウロペイン、オレウロペインアグリコン、オレウロペイン誘導体は主にオリーブの実、オリーブの葉、オリーブオイル等、オリーブ植物に含まれる成分を中心としたもので、既に本発明者らによってカテコールアミン誘発機能およびそれに付随する脂質代謝改善機能が見出されている（特許文献７）。また、オレウロペインについては血糖値上昇抑制、ＬＤＬ酸化抑制作用等の脂質代謝改善機能は報告されているが（特許文献８）、性ホルモンを分泌・促進する機能およびタンパク代謝改善等に関する機能は知られていなかった。 The oleuropein, oleuropein aglycone, and oleuropein derivatives, which are the products of the present invention, are mainly composed of components contained in olive plants such as olive fruits, olive leaves, olive oil, etc. An accompanying lipid metabolism improving function has been found (Patent Document 7). In addition, oleopain has been reported to improve lipid metabolism such as suppressing blood glucose level rise and inhibiting LDL oxidation (Patent Document 8), but it is known to function to secrete / promote sex hormones and to improve protein metabolism. It wasn't.
本発明は、タンパク代謝調節に有効であり、より汎用性の高い性ホルモン誘発機能を有する物質、および食品、薬品、健康食品等を提供し、それにより効率良く、タンパク代謝改善を可能にすることを目的とする。 The present invention is effective in regulating protein metabolism and provides a more versatile substance having a sex hormone-inducing function, and a food, medicine, health food, etc., thereby enabling efficient protein metabolism improvement. With the goal.
本発明者らは、上記目的のために鋭意検討した結果、オレウロペイン、或いはオレウロペインアグリコン、或いはオレウロペイン誘導体が性ホルモン分泌促進機能、また、これに付随して起こるタンパク代謝改善機能、さらには体質改善機能を有することを見出し本願発明を完成するに至った。
すなわち、本願発明は、オレウロペイン、オレウロペインアグリコン、オレウロペイン誘導体のうち少なくとも1つを有効成分として含有してなる性ホルモン誘発剤である。
さらに、本願発明は、前記性ホルモン誘発剤を用いてなるタンパク代謝改善及び／又は体質改善方法である。
As a result of intensive studies for the above-mentioned purpose, the present inventors have found that oleuropein, oleuropein aglycone, or oleuropein derivative has a function of promoting sex hormone secretion, a function of improving protein metabolism accompanying this, and a function of improving constitution. As a result, the present invention has been completed.
That is, the present invention is a sex hormone inducer comprising at least one of oleuropein, oleuropein aglycone, and oleuropein derivative as an active ingredient.
Furthermore, the present invention is a method for improving protein metabolism and / or improving constitution using the sex hormone inducer.
本発明のホルモン誘発機能を有する成分及び、飲食組成物は、優れたタンパク代謝改善作用を示し、それらを摂取することは優れた体質改善方法となる。 The component having the hormone-inducing function and the food and beverage composition of the present invention exhibit an excellent protein metabolism improving action, and taking them becomes an excellent constitution improving method.
ホルモンはその作用、分泌する器官、骨格となる構造などで分類されるが、タンパク代謝に関与するホルモンを代謝機能の観点からみると（1）タンパク同化（生合成）と（2）タンパク異化（分解）に分類できる。タンパク同化作用を持つものとしてはインシュリン、成長ホルモン、インシュリン様成長因子I、アドレナリン、アンドロゲン（テストステロン）などがあり、またタンパク異化作用を持つものとしてはグルココルチコイド（コルチコステロン）、グルカゴン、甲状腺刺激ホルモンなどが挙げられる。タンパク同化作用を持つホルモンが多量に分泌されるとタンパクの合成が促進され、逆にタンパク異化作用を持つホルモンが多量に分泌されるとタンパクの分解が促進される。
タンパク同化作用を持つホルモンのうち、アンドロゲンは性ホルモンの一種である。性ホルモンは精巣や卵巣など生殖腺と胎盤で合成・分泌されるステロイドホルモンで、アンドロゲンのほかにエストロゲン等がある。
Hormones are categorized by their actions, secreting organs, and skeletal structures. From the viewpoint of metabolic function, hormones involved in protein metabolism are (1) anabolic (biosynthesis) and (2) protein catabolism ( Decomposition). Those with anabolic activity include insulin, growth hormone, insulin-like growth factor I, adrenaline, androgen (testosterone), and those with protein catabolism include glucocorticoid (corticosterone), glucagon, thyroid stimulation Hormones. When a large amount of hormones with anabolic activity is secreted, protein synthesis is promoted, and conversely, when a large amount of hormones with protein catabolic activity is secreted, protein degradation is promoted.
Of the hormones with anabolic activity, androgen is a type of sex hormone. Sex hormones are steroid hormones synthesized and secreted in the gonads and placenta, such as testis and ovaries. In addition to androgens, there are estrogens.
アンドロゲンはテストステロンに代表される雄性ホルモンで、主に精巣で生合成され、思春期の男性性器の発育促進、骨格や筋肉の成長促進、性欲の亢進、他にも脳や精神面への作用を有している。テストステロンは、脳下垂体から分泌される黄体形成ホルモン（LH）と、視床下部から分泌される黄体形成ホルモン放出ホルモン（LHRH）によってその量が調節されている。すなわち、テストステロンが少ないとLHの分泌が増え精巣でのテストステロンが増産されるが、テストステロンが充分あるとLHの分泌が抑えられる。一方で、LHRHはLHの分泌量をコントロールしている。極端なダイエット等によって動物性食品の摂取が不足すると、テストステロンの原料となるコレステロールが不足し、テストステロンが分泌できず、慢性的な欠乏状態になることもあると言われている。女性においても副腎や卵巣でテストステロンが少量ながら分泌されている。テストステロンは筋肉増強作用があることから一部スポーツアスリートの間で医師の監視の下、体質改善目的で使用されることがあるが、ホルモン分泌を誘発する機能を持つ成分を食品の形態で摂取することは代謝におけるフィードバックの仕組みが充分に作用するため極めて安全性が高く、副作用の心配も少ない。 Androgens are male hormones typified by testosterone, which are biosynthesized mainly in the testis, promote male male genital development during puberty, promote skeletal and muscle growth, increase libido, and have other effects on the brain and mental aspects. Have. The amount of testosterone is regulated by luteinizing hormone (LH) secreted from the pituitary gland and luteinizing hormone releasing hormone (LHRH) secreted from the hypothalamus. That is, when testosterone is low, LH secretion increases and testosterone is produced in the testis, but when testosterone is sufficient, LH secretion is suppressed. On the other hand, LHRH controls the amount of LH secretion. It is said that if the intake of animal food is insufficient due to an extreme diet or the like, cholesterol as a raw material for testosterone is insufficient, testosterone cannot be secreted, and chronic deficiency may occur. Even in women, a small amount of testosterone is secreted in the adrenal glands and ovaries. Testosterone has muscle-strengthening effects and may be used by some sports athletes for the purpose of improving the constitution under the supervision of doctors. However, it takes ingredients in the form of food that have the function of inducing hormone secretion. This is very safe because the feedback mechanism in metabolism works well, and there is little worry about side effects.
このようにテストステロンは男女問わず広く体内の代謝調節に関わっており、バランス調節は健康維持には欠かせないことから、通常の食生活で体質改善効果のあるものがより求められている。テストステロンの分泌促進によってタンパク質代謝改善に伴う骨格や筋肉の成長促進だけでなく、正常な性欲の維持、他にも脳や精神面での障害克服など、体質改善に役立てることができる。 As described above, testosterone is widely involved in the regulation of metabolism in the body regardless of gender, and balance adjustment is indispensable for maintaining health. Therefore, there is a demand for a normal diet that has an effect of improving constitution. By promoting the secretion of testosterone, it can be used not only to promote the growth of the skeleton and muscles accompanying the improvement of protein metabolism, but also to improve the constitution, such as maintaining normal libido and overcoming brain and mental disorders.
テストステロンは生理的に非常に重要な機能を有しており、これらを利用することは産業上極めて有用である。 Testosterone has a physiologically very important function, and it is extremely useful industrially to use these.
本発明におけるオレウロペイン（Oleuropeine）は図１の一般式で表される物質で、オレウロペインアグリコンとは、オレウロペインのグルコースの部分がはずれた状態の物質である。またオレウロペイン誘導体とは、主にオレウロペイン及びそのアグリコンが酸化、或いは還元により変化したもので例えば図２〜６の一般式で表されるような物質である。
オレウロペインはその構成要素としてヒドロキシチロゾール（図７）とエレノール酸（図８、９）を含んでいるが、これらヒドロキシチロゾールとエレノール酸の結合体（エレノール酸のピラン環に結合する官能基の変化したもの、或いはピラン環そのものの開裂したものも含む）も、本発明に含まれる。
オレウロペインの詳細な作用機序は明確ではないが、ヒドロキシチロゾールとエレノール酸とのアシル結合部位から、エレノール酸のピラン環へ続く構造に起因する要素が作用に深く関与しているものと推測される。
Oleuropein in the present invention is a substance represented by the general formula of FIG. 1, and oleuropein aglycone is a substance in which the glucose portion of oleuropein is off. In addition, the oleuropein derivative is a substance in which oleuropein and its aglycone are mainly changed by oxidation or reduction, for example, a substance represented by the general formulas of FIGS.
Oleuropein contains hydroxytyrosol (Fig. 7) and elenolic acid (Figs. 8 and 9) as its constituents. The conjugate of hydroxytyrosol and elenolic acid (the functional group that binds to the pyran ring of elenolic acid). Also included are those that have changed, or those in which the pyran ring itself has been cleaved).
Although the detailed mechanism of action of oleuropein is not clear, it is speculated that the elements resulting from the structure following the pyran ring of elenolic acid from the acyl binding site of hydroxytyrosol and elenolic acid are deeply involved in the action. The
一般に配糖体は体内で吸収されるに伴い、その多くは糖部分が酵素により切り離されアグリコンの形をとることが知られている。従って、本発明のオレウロペインを経口摂取した場合、体内ではオレウロペインアグリコンの形で存在、作用している可能性が極めて高い。逆に、オレウロペインアグリコンの形で経口摂取した場合、作用強度の違いはあれ、オレウロペインと同種の作用が得られることとなる。また、オレウロペインをグルコシダーゼ酵素で処理した成分は、オレウロペインアグリコンに加えジアセト型オレウロペインアグリコンが含まれることがあり、従って、体内においてもオレウロペイン誘導体は、種々の形で存在しているものと考えられる。 In general, as glycosides are absorbed in the body, most of them are known to take the form of aglycone by the sugar moiety being cleaved by an enzyme. Therefore, when the oleuropein of the present invention is orally ingested, it is very likely that it exists and acts in the form of oleuropein aglycone in the body. Conversely, when taken orally in the form of oleuropein aglycone, the same type of action as oleuropein will be obtained, although there is a difference in action strength. In addition, components obtained by treating oleuropein with a glucosidase enzyme may include diaurete type oleuropein aglycone in addition to oleuropein aglycone. Therefore, it is considered that oleuropein derivatives exist in various forms in the body.
オレウロペイン、及びそのアグリコン、さらにはそれらの誘導体は天然にはオリーブ植物に多く含まれる。水、アルコール等の有機溶剤、油等により、オリーブ植物からこれら成分を抽出採取することができる。さらには、これらを必要により公知の方法で濃縮、乾固、精製して利用できる。特にオレウロペインは葉に多く、オリーブ植物の剪定、或いは伐採されたものを有効利用することもできる。
オリーブの実からオリーブ油を搾油する際には大量の植物水、処理水が発生するためこれも採取源となりうる。また、オリーブ油にもこれら成分が含まれており、油から採取、あるいは油そのものを利用することもできる。
他に構成成分を基質として合成により作られたものも使用可能である。
本発明の性ホルモン誘発剤は食品、健康食品等いずれの用途、形態でも利用できる。
Oleuropein and its aglycone and their derivatives are naturally abundant in olive plants. These components can be extracted and collected from olive plants with water, organic solvents such as alcohol, oil, and the like. Furthermore, these can be used by concentrating, drying and purifying by a known method if necessary. In particular, oleuropein is abundant in leaves, and it is possible to effectively use pruned or felled olive plants.
When olive oil is squeezed from olive fruits, a large amount of plant water and treated water are generated, which can be a source of collection. Olive oil also contains these components, which can be collected from the oil or used as such.
In addition, those made by synthesis using a component as a substrate can also be used.
The sex hormone inducer of the present invention can be used in any application and form such as food and health food.
以下に本発明の実施例を記載するが、本発明は、もとよりこれに限定されるものではない。
＜実施例１〜３、比較例１〜３＞
４週齢SD系雄ラットに実験食を２８日間ペアーフィーディングにより投与した。実験食はそれぞれ蛋白レベル４０％、２５％、１０％として、いずれも0.01％(W/W)のオレウロペイン（Extrasynthesis Geney フランスNo.0204）を配合した。比較例としてそれぞれの蛋白レベル食でオレウロペインを含まない組成のものを調製し摂食させた。
Although the Example of this invention is described below, this invention is not limited to this from the first.
<Examples 1-3, Comparative Examples 1-3>
The experimental diet was administered to 4-week-old SD male rats by pair feeding for 28 days. The experimental foods were mixed with 0.01% (W / W) oleuropein (Extrasynthesis Geney France No. 0204) at protein levels of 40%, 25% and 10%, respectively. As a comparative example, each protein-level food composition containing no oleuropein was prepared and fed.
２８日間の飼育後、体重及び各組織の重量増加、窒素出納、睾丸中のテストステロン量、血漿中のコルチコステロン濃度を測定した。コルチコステロンはげっ歯類においてタンパク異化作用を持つ糖質コルチコロイドの代表的なホルモンの一種である。 After breeding for 28 days, body weight and weight increase of each tissue, nitrogen balance, testosterone level in testicles, and corticosterone concentration in plasma were measured. Corticosterone is one of the typical hormones of glucocorticoids that have protein catabolism in rodents.
窒素出納では、オレウロペイン含有の実験食摂取群では特に４０％カゼイン食において窒素取り込み量が有意に高く、また２５％、１０％カゼイン食においても窒素取り込み量が高い傾向がみられた。すなわちタンパク質の生合成量が高いことが示唆された。
オレウロペインを含有する実験食の摂取によって、性ホルモンであるテストステロンの分泌量の増加がみられ、またテストステロンのタンパク同化作用に起因するタンパクの生合成が促進された。
オレウロペイン含有の実験食摂取群では特に４０％カゼイン食においてタンパク同化作用を持つテストステロンが有意に増加しており、また２５％、１０％カゼイン食においてもテストステロンの増加傾向がみられた。一方で、タンパク異化作用を持つコルチコステロンは、オレウロペイン含有の実験食摂取群では特に４０％カゼイン食において有意に減少しており、また２５％、１０％カゼイン食においても比較群に比べて少ない傾向がみられた。
In the nitrogen balance, the nitrogen intake was significantly higher especially in the 40% casein diet, and the 25% and 10% casein diet tended to have a higher nitrogen uptake in the experimental diet group containing oleuropein. That is, it was suggested that the amount of protein biosynthesis was high.
Ingestion of an experimental diet containing oleuropein increased the secretion of testosterone, a sex hormone, and promoted protein biosynthesis resulting from the anabolic action of testosterone.
The testosterone having an anabolic effect was significantly increased especially in the 40% casein diet in the experimental diet intake group containing oleuropein, and the testosterone increased in the 25% and 10% casein diet. On the other hand, corticosterone having a protein catabolism is significantly decreased particularly in the 40% casein diet in the oleuropein-containing experimental diet group, and also less in the 25% and 10% casein diets than in the comparison group. There was a trend.
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2008116644A JP5264269B2 (en) | 2008-04-28 | 2008-04-28 | Sex hormone inducer and protein metabolism improvement and constitution improvement method using the same |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2008116644A JP5264269B2 (en) | 2008-04-28 | 2008-04-28 | Sex hormone inducer and protein metabolism improvement and constitution improvement method using the same |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2009263295A JP2009263295A (en) | 2009-11-12 |
| JP5264269B2 true JP5264269B2 (en) | 2013-08-14 |
Family
ID=41389619
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2008116644A Active JP5264269B2 (en) | 2008-04-28 | 2008-04-28 | Sex hormone inducer and protein metabolism improvement and constitution improvement method using the same |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP5264269B2 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20220119335A1 (en) * | 2019-02-13 | 2022-04-21 | Omphax SA | Method for obtaining oleacein and oleomissional type secoiridoids and for producing respective pharmaceutical preparations |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105491896A (en) * | 2013-08-27 | 2016-04-13 | 三得利控股株式会社 | Clock gene expression level modifier |
| GR1010545B (en) * | 2019-02-13 | 2023-09-25 | Προκοπιος Παναγιωτη Μαγιατης | Method for obtaining oleocanthal secoiridoids and method for producing respective pharmaceutical preparations |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP5024579B2 (en) * | 2003-11-26 | 2012-09-12 | 株式会社Ｊ−オイルミルズ | Catecholamine inducer |
-
2008
- 2008-04-28 JP JP2008116644A patent/JP5264269B2/en active Active
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20220119335A1 (en) * | 2019-02-13 | 2022-04-21 | Omphax SA | Method for obtaining oleacein and oleomissional type secoiridoids and for producing respective pharmaceutical preparations |
Also Published As
| Publication number | Publication date |
|---|---|
| JP2009263295A (en) | 2009-11-12 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5390594B2 (en) | Preparation and use of plant extracts of Solanum glaucophyllum containing high concentrations of 1,25-dihydroxyvitamin D3 glycoside and quercetin glycoside | |
| Ali et al. | Reproductive hormonal status of rats treated with date pits | |
| US20130216512A1 (en) | Stable aqueous suspension | |
| HUT77522A (en) | Sterol compositions from pulping soap | |
| CN107771946A (en) | A kind of formula milk and its production method for contributing to middle-aged and old cardiovascular and cerebrovascular health | |
| Mathe et al. | Effects of the thyroid state on cholesterol metabolism in the rat | |
| EP0916342B1 (en) | A medicament for treating obesity and improving lipid metabolism | |
| UA78699C2 (en) | Use of bile acid or bile salt fatty acid conjugates for decreasing cholesterol blood content, treating fatty liver, hyperglycemia, and diabetes | |
| JP5264269B2 (en) | Sex hormone inducer and protein metabolism improvement and constitution improvement method using the same | |
| JP4002654B2 (en) | Blood lipid improving agent, cyclic AMP phosphodiesterase inhibitor, obesity preventive / eliminating agent, food and beverage, and skin external preparation | |
| US20140294999A1 (en) | Natural weight reduction health composition and application thereof | |
| EP2705762B1 (en) | Biologically active dietary supplement for normalizing the androgen level in men and the overall condition and reducing obesity | |
| JP2004256513A (en) | Agent for increasing amount of muscle | |
| Negm | The possible protective role of powder cuttlefish bone, crabshell and eggshell on osteoporotic rats | |
| JP2004000171A (en) | Functional food product containing maca | |
| Elhassaneen et al. | The potential effects of reishi mushroom (Ganoderma lucidum) consumption on bone health indices and serum minerals profile disorders induced by CCl4 on rats | |
| JPH06192072A (en) | Pharmaceutical preparation containing mixture of higher primary fatty alcohols used for treatment of hypercholesterolemia and hyperlipoproteinemia type ii in animal and human being and stimulus of sexial behavior | |
| JP4325908B2 (en) | Lipolysis accelerator, skin external preparation and food and drink using the same | |
| Morita et al. | Dietary fiber and fat-derivatives prevent mineral oil toxicity in rats by the same mechanism | |
| JP2007297370A (en) | Glucose level rise inhibitor | |
| Farvin et al. | Supplementation of squalene attenuates experimentally induced myocardial infarction in rats | |
| JP6941913B2 (en) | A composition for preventing, ameliorating or treating precocious puberty containing an extract of Japanese Chin and Japanese Chin as an active ingredient. | |
| Bernao et al. | Effect of different doses of chromium picolinate on protein metabolism in infant rats | |
| WO2007116980A1 (en) | Suppressor of increase in blood glucose level | |
| Peterson et al. | Effects of soy isoflavone consumption on bone structure and milk mineral concentration in a rat model of lactation-associated bone loss |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20101110 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20121030 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20121203 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20121204 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20130108 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20130111 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20130423 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20130430 |
|
| R150 | Certificate of patent or registration of utility model |
Free format text: JAPANESE INTERMEDIATE CODE: R150 Ref document number: 5264269 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |