JP2011244819A - エストロゲン分泌促進及び女性生殖器組織細胞再生のための組成物 - Google Patents
エストロゲン分泌促進及び女性生殖器組織細胞再生のための組成物 Download PDFInfo
- Publication number
- JP2011244819A JP2011244819A JP2011127661A JP2011127661A JP2011244819A JP 2011244819 A JP2011244819 A JP 2011244819A JP 2011127661 A JP2011127661 A JP 2011127661A JP 2011127661 A JP2011127661 A JP 2011127661A JP 2011244819 A JP2011244819 A JP 2011244819A
- Authority
- JP
- Japan
- Prior art keywords
- extract
- composition
- estrogen
- present
- group
- 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.)
- Pending
Links
- 239000000262 estrogen Substances 0.000 title abstract description 74
- 229940011871 estrogen Drugs 0.000 title abstract description 74
- 230000028327 secretion Effects 0.000 title abstract description 27
- 238000000034 method Methods 0.000 title description 11
- 210000000056 organ Anatomy 0.000 title description 4
- 230000001172 regenerating effect Effects 0.000 title description 4
- 230000001568 sexual effect Effects 0.000 title description 3
- 239000000284 extract Substances 0.000 claims abstract description 89
- 239000000203 mixture Substances 0.000 claims abstract description 73
- 239000004475 Arginine Substances 0.000 claims abstract description 4
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims abstract description 4
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims abstract description 4
- 239000011575 calcium Substances 0.000 claims abstract description 4
- 229910052791 calcium Inorganic materials 0.000 claims abstract description 4
- 241000331432 Cynanchum wilfordii Species 0.000 claims abstract description 3
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 claims abstract description 3
- 239000004480 active ingredient Substances 0.000 claims description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 9
- 239000012528 membrane Substances 0.000 claims description 7
- 238000000108 ultra-filtration Methods 0.000 claims description 7
- 208000017657 Menopausal disease Diseases 0.000 claims description 5
- 240000007594 Oryza sativa Species 0.000 claims description 5
- 235000007164 Oryza sativa Nutrition 0.000 claims description 5
- 208000001132 Osteoporosis Diseases 0.000 claims description 5
- 235000013305 food Nutrition 0.000 claims description 5
- 235000009566 rice Nutrition 0.000 claims description 5
- 230000002265 prevention Effects 0.000 claims description 4
- 230000001457 vasomotor Effects 0.000 claims description 4
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 3
- 239000004472 Lysine Substances 0.000 claims description 3
- 206010016825 Flushing Diseases 0.000 claims description 2
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 claims description 2
- 241001192908 Phlomis umbrosa Species 0.000 claims description 2
- 238000001914 filtration Methods 0.000 claims description 2
- 230000035900 sweating Effects 0.000 claims description 2
- 210000002229 urogenital system Anatomy 0.000 claims description 2
- 241000332371 Abutilon x hybridum Species 0.000 claims 1
- 208000008454 Hyperhidrosis Diseases 0.000 claims 1
- 206010047791 Vulvovaginal dryness Diseases 0.000 claims 1
- 230000005856 abnormality Effects 0.000 claims 1
- 239000000654 additive Substances 0.000 claims 1
- 230000000996 additive effect Effects 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 16
- 230000001737 promoting effect Effects 0.000 abstract description 12
- 206010028980 Neoplasm Diseases 0.000 abstract description 5
- 201000011510 cancer Diseases 0.000 abstract description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 5
- 229940088597 hormone Drugs 0.000 abstract description 5
- 239000005556 hormone Substances 0.000 abstract description 5
- 210000001752 female genitalia Anatomy 0.000 abstract description 3
- 230000035755 proliferation Effects 0.000 abstract description 3
- 230000008929 regeneration Effects 0.000 abstract description 3
- 238000011069 regeneration method Methods 0.000 abstract description 3
- 208000024891 symptom Diseases 0.000 abstract description 2
- 230000002411 adverse Effects 0.000 abstract 1
- KWIUHFFTVRNATP-UHFFFAOYSA-N glycine betaine Chemical compound C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 abstract 1
- 241000703121 Campanula rotundifolia Species 0.000 description 32
- 210000001519 tissue Anatomy 0.000 description 15
- 241000700159 Rattus Species 0.000 description 13
- 210000001672 ovary Anatomy 0.000 description 12
- DNXHEGUUPJUMQT-UHFFFAOYSA-N (+)-estrone Natural products OC1=CC=C2C3CCC(C)(C(CC4)=O)C4C3CCC2=C1 DNXHEGUUPJUMQT-UHFFFAOYSA-N 0.000 description 11
- VOXZDWNPVJITMN-ZBRFXRBCSA-N 17β-estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 VOXZDWNPVJITMN-ZBRFXRBCSA-N 0.000 description 11
- DNXHEGUUPJUMQT-CBZIJGRNSA-N Estrone Chemical compound OC1=CC=C2[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1 DNXHEGUUPJUMQT-CBZIJGRNSA-N 0.000 description 11
- 210000004027 cell Anatomy 0.000 description 11
- 210000004392 genitalia Anatomy 0.000 description 11
- 244000066764 Ailanthus triphysa Species 0.000 description 10
- 229960003399 estrone Drugs 0.000 description 10
- 239000008194 pharmaceutical composition Substances 0.000 description 10
- 229960005309 estradiol Drugs 0.000 description 9
- 229930182833 estradiol Natural products 0.000 description 8
- 238000004519 manufacturing process Methods 0.000 description 8
- 210000003739 neck Anatomy 0.000 description 8
- 210000004369 blood Anatomy 0.000 description 7
- 239000008280 blood Substances 0.000 description 7
- 230000009245 menopause Effects 0.000 description 7
- 238000002657 hormone replacement therapy Methods 0.000 description 6
- 230000001965 increasing effect Effects 0.000 description 6
- 210000002966 serum Anatomy 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 5
- 229940069765 bean extract Drugs 0.000 description 5
- 238000000605 extraction Methods 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 241000196324 Embryophyta Species 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 244000061456 Solanum tuberosum Species 0.000 description 4
- 235000002595 Solanum tuberosum Nutrition 0.000 description 4
- 230000037396 body weight Effects 0.000 description 4
- 230000001076 estrogenic effect Effects 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 230000012010 growth Effects 0.000 description 4
- 235000013402 health food Nutrition 0.000 description 4
- 239000002243 precursor Substances 0.000 description 4
- 230000002062 proliferating effect Effects 0.000 description 4
- 210000004291 uterus Anatomy 0.000 description 4
- PROQIPRRNZUXQM-UHFFFAOYSA-N (16alpha,17betaOH)-Estra-1,3,5(10)-triene-3,16,17-triol Natural products OC1=CC=C2C3CCC(C)(C(C(O)C4)O)C4C3CCC2=C1 PROQIPRRNZUXQM-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 102000008186 Collagen Human genes 0.000 description 3
- 108010035532 Collagen Proteins 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- AFCARXCZXQIEQB-UHFFFAOYSA-N N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CCNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 AFCARXCZXQIEQB-UHFFFAOYSA-N 0.000 description 3
- 206010067572 Oestrogenic effect Diseases 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 238000005899 aromatization reaction Methods 0.000 description 3
- 150000003943 catecholamines Chemical class 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 229920001436 collagen Polymers 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
- PROQIPRRNZUXQM-ZXXIGWHRSA-N estriol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H]([C@H](O)C4)O)[C@@H]4[C@@H]3CCC2=C1 PROQIPRRNZUXQM-ZXXIGWHRSA-N 0.000 description 3
- 229960001348 estriol Drugs 0.000 description 3
- 239000005445 natural material Substances 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 230000001850 reproductive effect Effects 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 206010006187 Breast cancer Diseases 0.000 description 2
- 208000026310 Breast neoplasm Diseases 0.000 description 2
- 208000024172 Cardiovascular disease Diseases 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- 244000299452 Gouania lupuloides Species 0.000 description 2
- 235000000292 Gouania lupuloides Nutrition 0.000 description 2
- 206010027304 Menopausal symptoms Diseases 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- 235000002791 Panax Nutrition 0.000 description 2
- 241000208343 Panax Species 0.000 description 2
- 206010036790 Productive cough Diseases 0.000 description 2
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
- 208000002495 Uterine Neoplasms Diseases 0.000 description 2
- 210000000577 adipose tissue Anatomy 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
- 239000003098 androgen Substances 0.000 description 2
- AEMFNILZOJDQLW-QAGGRKNESA-N androst-4-ene-3,17-dione Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1 AEMFNILZOJDQLW-QAGGRKNESA-N 0.000 description 2
- 229960005471 androstenedione Drugs 0.000 description 2
- AEMFNILZOJDQLW-UHFFFAOYSA-N androstenedione Natural products O=C1CCC2(C)C3CCC(C)(C(CC4)=O)C4C3CCC2=C1 AEMFNILZOJDQLW-UHFFFAOYSA-N 0.000 description 2
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- 235000001465 calcium Nutrition 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 230000007850 degeneration Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 230000005906 menstruation Effects 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- 239000002207 metabolite Substances 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- 229930014626 natural product Natural products 0.000 description 2
- 230000002611 ovarian Effects 0.000 description 2
- 230000002093 peripheral effect Effects 0.000 description 2
- 239000008196 pharmacological composition Substances 0.000 description 2
- 239000003075 phytoestrogen Substances 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 208000024794 sputum Diseases 0.000 description 2
- 210000003802 sputum Anatomy 0.000 description 2
- 150000003431 steroids Chemical class 0.000 description 2
- 230000002195 synergetic effect Effects 0.000 description 2
- 230000001256 tonic effect Effects 0.000 description 2
- 210000002700 urine Anatomy 0.000 description 2
- 206010046766 uterine cancer Diseases 0.000 description 2
- 210000001215 vagina Anatomy 0.000 description 2
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- 229940058015 1,3-butylene glycol Drugs 0.000 description 1
- OHVLMTFVQDZYHP-UHFFFAOYSA-N 1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)-2-[4-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]piperazin-1-yl]ethanone Chemical compound N1N=NC=2CN(CCC=21)C(CN1CCN(CC1)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)=O OHVLMTFVQDZYHP-UHFFFAOYSA-N 0.000 description 1
- VZSRBBMJRBPUNF-UHFFFAOYSA-N 2-(2,3-dihydro-1H-inden-2-ylamino)-N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]pyrimidine-5-carboxamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C(=O)NCCC(N1CC2=C(CC1)NN=N2)=O VZSRBBMJRBPUNF-UHFFFAOYSA-N 0.000 description 1
- WZFUQSJFWNHZHM-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)CC(=O)N1CC2=C(CC1)NN=N2 WZFUQSJFWNHZHM-UHFFFAOYSA-N 0.000 description 1
- IHCCLXNEEPMSIO-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperidin-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C1CCN(CC1)CC(=O)N1CC2=C(CC1)NN=N2 IHCCLXNEEPMSIO-UHFFFAOYSA-N 0.000 description 1
- 102000040125 5-hydroxytryptamine receptor family Human genes 0.000 description 1
- 108091032151 5-hydroxytryptamine receptor family Proteins 0.000 description 1
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- 229920000856 Amylose Polymers 0.000 description 1
- 206010003210 Arteriosclerosis Diseases 0.000 description 1
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 1
- 241000208671 Campanulaceae Species 0.000 description 1
- 206010011732 Cyst Diseases 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 241000238557 Decapoda Species 0.000 description 1
- 206010012289 Dementia Diseases 0.000 description 1
- 244000169962 Dioscorea macrostachya Species 0.000 description 1
- 235000004868 Dioscorea macrostachya Nutrition 0.000 description 1
- 102000015554 Dopamine receptor Human genes 0.000 description 1
- 108050004812 Dopamine receptor Proteins 0.000 description 1
- WKRLQDKEXYKHJB-UHFFFAOYSA-N Equilin Natural products OC1=CC=C2C3CCC(C)(C(CC4)=O)C4C3=CCC2=C1 WKRLQDKEXYKHJB-UHFFFAOYSA-N 0.000 description 1
- 102000007594 Estrogen Receptor alpha Human genes 0.000 description 1
- 108010007005 Estrogen Receptor alpha Proteins 0.000 description 1
- 102000000509 Estrogen Receptor beta Human genes 0.000 description 1
- 108010041356 Estrogen Receptor beta Proteins 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- 102000018997 Growth Hormone Human genes 0.000 description 1
- 108010051696 Growth Hormone Proteins 0.000 description 1
- 102000023108 LH Receptors Human genes 0.000 description 1
- 108010011942 LH Receptors Proteins 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 241000207923 Lamiaceae Species 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- JYDNKGUBLIKNAM-UHFFFAOYSA-N Oxyallobutulin Natural products C1CC(=O)C(C)(C)C2CCC3(C)C4(C)CCC5(CO)CCC(C(=C)C)C5C4CCC3C21C JYDNKGUBLIKNAM-UHFFFAOYSA-N 0.000 description 1
- 235000008124 Picea excelsa Nutrition 0.000 description 1
- 240000000020 Picea glauca Species 0.000 description 1
- 235000008127 Picea glauca Nutrition 0.000 description 1
- 244000274050 Platycodon grandiflorum Species 0.000 description 1
- 235000006753 Platycodon grandiflorum Nutrition 0.000 description 1
- 241000219050 Polygonaceae Species 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- -1 Saponin glycosides Chemical class 0.000 description 1
- 241000269851 Sarda sarda Species 0.000 description 1
- 108010089417 Sex Hormone-Binding Globulin Proteins 0.000 description 1
- 102000034755 Sex Hormone-Binding Globulin Human genes 0.000 description 1
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 208000008312 Tooth Loss Diseases 0.000 description 1
- 208000025609 Urogenital disease Diseases 0.000 description 1
- 206010046782 Uterine enlargement Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 210000004404 adrenal cortex Anatomy 0.000 description 1
- 230000001919 adrenal effect Effects 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 102000030619 alpha-1 Adrenergic Receptor Human genes 0.000 description 1
- 108020004102 alpha-1 Adrenergic Receptor Proteins 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 230000000954 anitussive effect Effects 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 230000001754 anti-pyretic effect Effects 0.000 description 1
- 229940124584 antitussives Drugs 0.000 description 1
- 239000006286 aqueous extract Substances 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 208000011775 arteriosclerosis disease Diseases 0.000 description 1
- 238000011888 autopsy Methods 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- FVWJYYTZTCVBKE-ROUWMTJPSA-N betulin Chemical compound C1C[C@H](O)C(C)(C)[C@@H]2CC[C@@]3(C)[C@]4(C)CC[C@@]5(CO)CC[C@@H](C(=C)C)[C@@H]5[C@H]4CC[C@@H]3[C@]21C FVWJYYTZTCVBKE-ROUWMTJPSA-N 0.000 description 1
- MVIRREHRVZLANQ-UHFFFAOYSA-N betulin Natural products CC(=O)OC1CCC2(C)C(CCC3(C)C2CC=C4C5C(CCC5(CO)CCC34C)C(=C)C)C1(C)C MVIRREHRVZLANQ-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000023555 blood coagulation Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 235000019437 butane-1,3-diol Nutrition 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 229960001714 calcium phosphate Drugs 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 239000000378 calcium silicate Substances 0.000 description 1
- 229910052918 calcium silicate Inorganic materials 0.000 description 1
- 229960003340 calcium silicate Drugs 0.000 description 1
- 235000012241 calcium silicate Nutrition 0.000 description 1
- OYACROKNLOSFPA-UHFFFAOYSA-N calcium;dioxido(oxo)silane Chemical compound [Ca+2].[O-][Si]([O-])=O OYACROKNLOSFPA-UHFFFAOYSA-N 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 208000031513 cyst Diseases 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical compound C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000035622 drinking Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 210000004696 endometrium Anatomy 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- QTTMOCOWZLSYSV-QWAPEVOJSA-M equilin sodium sulfate Chemical compound [Na+].[O-]S(=O)(=O)OC1=CC=C2[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4C3=CCC2=C1 QTTMOCOWZLSYSV-QWAPEVOJSA-M 0.000 description 1
- 239000003797 essential amino acid Substances 0.000 description 1
- 235000020776 essential amino acid Nutrition 0.000 description 1
- 229940010344 estradiol / estrone Drugs 0.000 description 1
- 239000003687 estradiol congener Substances 0.000 description 1
- VUCAHVBMSFIGAI-ZFINNJDLSA-M estrone sodium sulfate Chemical compound [Na+].[O-]S(=O)(=O)OC1=CC=C2[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1 VUCAHVBMSFIGAI-ZFINNJDLSA-M 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 239000003172 expectorant agent Substances 0.000 description 1
- 230000003419 expectorant effect Effects 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 238000011010 flushing procedure Methods 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 235000015203 fruit juice Nutrition 0.000 description 1
- 230000008717 functional decline Effects 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 229940014259 gelatin Drugs 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000001727 glucose Nutrition 0.000 description 1
- 150000008134 glucuronides Chemical group 0.000 description 1
- 229930182470 glycoside Natural products 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 239000000122 growth hormone Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
- 238000010335 hydrothermal treatment Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 238000005805 hydroxylation reaction Methods 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 206010022437 insomnia Diseases 0.000 description 1
- 230000008069 intimal proliferation Effects 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229940069445 licorice extract Drugs 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 230000037356 lipid metabolism Effects 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 210000005075 mammary gland Anatomy 0.000 description 1
- 230000023247 mammary gland development Effects 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 229940101513 menest Drugs 0.000 description 1
- 230000003821 menstrual periods Effects 0.000 description 1
- 230000037353 metabolic pathway Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 210000000754 myometrium Anatomy 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 231100000957 no side effect Toxicity 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 238000009806 oophorectomy Methods 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 229940127234 oral contraceptive Drugs 0.000 description 1
- 239000003539 oral contraceptive agent Substances 0.000 description 1
- 210000003101 oviduct Anatomy 0.000 description 1
- 230000016087 ovulation Effects 0.000 description 1
- 235000012771 pancakes Nutrition 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 229930000184 phytotoxin Natural products 0.000 description 1
- 210000002826 placenta Anatomy 0.000 description 1
- 239000000419 plant extract Substances 0.000 description 1
- 239000003123 plant toxin Substances 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 229940063238 premarin Drugs 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 229960003387 progesterone Drugs 0.000 description 1
- 239000000186 progesterone Substances 0.000 description 1
- 102000003998 progesterone receptors Human genes 0.000 description 1
- 108090000468 progesterone receptors Proteins 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 239000001397 quillaja saponaria molina bark Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 229930182490 saponin Natural products 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 230000035807 sensation Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 230000009645 skeletal growth Effects 0.000 description 1
- 230000012488 skeletal system development Effects 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 230000003637 steroidlike Effects 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 210000001550 testis Anatomy 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
- 238000009777 vacuum freeze-drying Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/27—Asclepiadaceae (Milkweed family), e.g. hoya
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/15—Vitamins
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/16—Inorganic salts, minerals or trace elements
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
- A61K36/232—Angelica
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/34—Campanulaceae (Bellflower family)
- A61K36/346—Platycodon
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/12—Drugs for genital or sexual disorders; Contraceptives for climacteric disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/16—Emollients or protectives, e.g. against radiation
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
-
- 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
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
- A61P5/30—Oestrogens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Mycology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Botany (AREA)
- Microbiology (AREA)
- Medical Informatics (AREA)
- Biotechnology (AREA)
- Alternative & Traditional Medicine (AREA)
- Epidemiology (AREA)
- Polymers & Plastics (AREA)
- Nutrition Science (AREA)
- Food Science & Technology (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Diabetes (AREA)
- Physical Education & Sports Medicine (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Inorganic Chemistry (AREA)
- Neurosurgery (AREA)
- Hospice & Palliative Care (AREA)
- Dermatology (AREA)
- Psychiatry (AREA)
- Pregnancy & Childbirth (AREA)
- Gynecology & Obstetrics (AREA)
- Rheumatology (AREA)
Abstract
【解決手段】桔梗(Platycodi Radix)抽出物及び白何首烏(Cynanchum wilfordii)抽出物からなる群から選択される一つまたはそれ以上を有効成分とし、さらにカルシウム、アルギニン及びリシンからなる群から選択される一つまたはそれ以上の成分を含む組成物。当該抽出物は、従来のホルモン代替療法に使用されるエストロゲン代替剤に比べ、癌発生のような副作用をほとんど生じることなく、優れたエストロゲン分泌促進効果並びに女性生殖器組織細胞の再生及び増殖効果を奏し、エストロゲンの分泌の足りない閉経期以後の女性の様々な症状に適用することができると共に、不純物がほとんどなく有効成分の含量が高い。
【選択図】図1
Description
本発明の桔梗、白何首烏及び続断は、キョンドン市場(ソウル、大韓民国)から購入し、抽出物の製造に使用した。
実施例1−1:限外濾過膜を利用した桔梗の低分子量抽出物の製造
乾燥された桔梗50gを水1.5lに入れて、常温以上の温度で約2時間抽出し、水溶性抽出液を得た。前記抽出液を濃縮し、嵩を最終500mlまで減らした。この溶液を遠心分離機で10分間3,000rpmで遠心分離した後、上清液を攪拌セル(stirred cell)装置(アミコン(Amicon)社、アメリカ)を利用し3気圧の窒素下で分子量カットオフ(MWCO)100,000の限外濾過膜に通過させた。その後、これを乾燥し、表1に示した量の粉末を得た。
表2に示したような組成により、本発明の桔梗抽出物を含む経口投与用組成物を製造した。
白何首烏の根部位を使用し、前記実施例1−1及び1−2と同様な方法により白何首烏抽出物を製造し、これを含む経口投与用組成物を製造した。前記白何首烏抽出物の量は、表3に示した通りである。また、本発明の経口投与用組成物の組成は、表4に示した。
桔梗50g、白何首烏の根部位25g及び続断の根部位25gを使用し、前記実施例1−1及び1−2と同様な方法により桔梗、白何首烏及び続断を全部含む抽出物を製造し、これを含む経口投与用組成物を製造した。前記抽出物の量は、表5に示した通りである。また、本発明の経口投与用組成物の組成は、表6に示した。
本発明の組成物の効果を検証するために、雌ラットを利用し、前記実施例1、実施例2及び実施例3から製造された本発明の組成物を経口投与して、時間経過によるエストロゲン血中濃度及び生殖器の重量を測定して、解剖学的及び病理組織学的検査を行った。
平均体重300gの51週齢雌ラット70匹の左側卵巣を部分摘出しエストロゲン分泌量が少なくなるように誘導して、群別10匹ずつ、体重が均等に分配されるように順位化した体重を利用し無作為に七つの群(G1、G2、G3、G4、G5、G6及びG7)に分けて、G2群には、実施例1−2の組成物100mg/kgを、G3群には、実施例1−2の組成物1,000mg/kgを、G4群には、実施例2の組成物100mg/kgを、G5群には、実施例2の組成物1,000mg/kgを、G6群には、実施例3の組成物100mg/kgを、G7群には、実施例3の組成物1,000mg/kgを、それぞれ注射用蒸留水に溶解及び懸濁して10mg/kgずつ経口投与した。また、G1群は、対照群として、注射用蒸留水10mg/kgを経口投与した。投与方法は、ラットを固定し、金属製経口投与用ゾンデを利用し胃内に直接注入した。投与開始時期は、卵巣摘出後10日後であり、投与回数は、一回/日、7日/週にして約5週間投与した。
投与開始から8週後、各群のラットを剖検する前に一晩絶食した後、後大静脈から採血し、これを室温で15分間静置し凝固させた後、3,000rpmで10分間遠心分離して血清を分離した。分離された血清は、−70°Cに保管してから1470 wizard γ counter(Perkin Elmer Life Science)を使用し検査した。ラットの血中エストロゲンの定量は、EIA(enzyme immunoassay)キット(DSL、アメリカ)を利用して行った。前記実験の結果を表7に示した。
投与開始から8週後、各群のラットを剖検して、電子天平(BP310S、sartorius)を利用し、左側卵巣及び子宮の重量を測定した。実験の結果は表8に示されている。
前記実施例3の組成物を投与した群及び対照群を対象に剖検して、目視で解剖学的特徴を調べた。その結果、子宮の膨大が、対照群のG1群では2匹、100mg/kg投与群のG6群では3匹及び1,000mg/kg投与群のG7群では5匹と観察され、容量相関性を有して増加した。また、卵巣の黒色の嚢胞が、対照群では観察されなかったが、G6群では2匹、G7群では1匹が観察された。
Claims (6)
- 桔梗(Platycodi Radix)抽出物及び白何首烏(Cynanchum wilfordii)抽出物からなる群から選択される一つまたはそれ以上を有効成分として含む閉経期疾患の治療または予防のための組成物の、食品または機能性食品に対する添加剤としての使用。
- 前記組成物は、続断(Phlomis umbrosa)抽出物を有効成分としてさらに含むことを特徴とする、請求項1に記載の使用。
- 前記抽出物の含量は、前記組成物の総重量に対し20〜80重量%であることを特徴とする、請求項1に記載の使用。
- 前記組成物は、カルシウム、アルギニン及びリシンからなる群から選択される一つまたはそれ以上の成分をさらに含むことを特徴とする、請求項1に記載の使用。
- 前記抽出物は、桔梗または白何首烏を熱水処理した後、熱水抽出液を分子量カットオフ50,000〜100,000の限外濾過膜により濾過し得られた活性分画であることを特徴とする、請求項1に記載の使用。
- 前記閉経期疾患は、血管運動不安定による顔面紅潮、夜間の発汗、膣乾燥、骨多孔症、または泌尿生殖器系異常であることを特徴とする、請求項1に記載の使用。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR1020020046327A KR100382040B1 (en) | 2002-08-06 | 2002-08-06 | Composition for stimulating estrogen secretion and regenerating female reproductive tissue cells |
KR10-2002-0046327 | 2002-08-06 |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2004525869A Division JP4820548B2 (ja) | 2002-08-06 | 2003-08-06 | エストロゲン分泌促進及び女性生殖器組織細胞再生のための組成物 |
Publications (1)
Publication Number | Publication Date |
---|---|
JP2011244819A true JP2011244819A (ja) | 2011-12-08 |
Family
ID=36932208
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2004525869A Expired - Lifetime JP4820548B2 (ja) | 2002-08-06 | 2003-08-06 | エストロゲン分泌促進及び女性生殖器組織細胞再生のための組成物 |
JP2011127661A Pending JP2011244819A (ja) | 2002-08-06 | 2011-06-07 | エストロゲン分泌促進及び女性生殖器組織細胞再生のための組成物 |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2004525869A Expired - Lifetime JP4820548B2 (ja) | 2002-08-06 | 2003-08-06 | エストロゲン分泌促進及び女性生殖器組織細胞再生のための組成物 |
Country Status (5)
Country | Link |
---|---|
US (3) | US20060051433A1 (ja) |
JP (2) | JP4820548B2 (ja) |
KR (1) | KR100382040B1 (ja) |
AU (1) | AU2003251185A1 (ja) |
WO (1) | WO2004012754A1 (ja) |
Families Citing this family (19)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR100764401B1 (ko) | 2005-04-04 | 2007-10-05 | 주식회사 보고에프앤디 | 누에 번데기 열수추출물을 함유한 에스트로젠 활성화 작용을 갖는 기능성 식품 |
KR100585445B1 (ko) * | 2005-06-17 | 2006-06-07 | 신준식 | 혼합 생약재를 이용한 골질환 예방 및 치료용 약제 조성물 |
KR101106110B1 (ko) * | 2009-03-23 | 2012-01-18 | (주)내츄럴엔도텍 | 불면증 예방 또는 치료용 조성물 |
JP5658479B2 (ja) * | 2009-04-27 | 2015-01-28 | 株式会社岩出菌学研究所 | 脂肪減少等の活性を示す組成物 |
TWI504394B (zh) | 2011-04-29 | 2015-10-21 | Ind Tech Res Inst | 安托芬之製備方法 |
CN102600428A (zh) * | 2012-03-29 | 2012-07-25 | 常熟市常福有机复合肥有限公司 | 用于治疗急性盆腔炎的中草药及制备方法 |
KR101544532B1 (ko) * | 2013-10-17 | 2015-08-17 | 고려대학교 산학협력단 | 백수오 추출물을 포함하는 여성 갱년기 질환의 예방 또는 치료용 조성물 |
CN104000909A (zh) * | 2014-05-27 | 2014-08-27 | 朱艳茹 | 一种治疗腰间盘突出的中药 |
CN104069443A (zh) * | 2014-07-17 | 2014-10-01 | 卢士海 | 一种治疗急性化脓性骨髓炎的中药及制备方法 |
CN104983767B (zh) * | 2015-06-24 | 2018-11-23 | 江苏天晟药业股份有限公司 | 一种昆明杯冠藤总皂苷的制备方法 |
KR101794607B1 (ko) * | 2015-07-10 | 2017-11-07 | 주식회사 브레인온 | 속단 및 백수오 추출물을 유효성분으로 포함하는 운동능력 및 근육 증진용 조성물 |
CN104971077B (zh) * | 2015-07-31 | 2019-01-01 | 江苏天晟药业股份有限公司 | 一种昆明杯冠藤总皂苷的新用途 |
KR101956783B1 (ko) * | 2016-11-15 | 2019-03-13 | 대한민국(농촌진흥청장) | 백수오 추출물 또는 백수오 조다당 추출물을 유효성분으로 함유하는 면역기능 향상을 위한 조성물 |
KR102119022B1 (ko) | 2017-06-30 | 2020-06-12 | 동국대학교 경주캠퍼스 산학협력단 | 생약재 추출물을 유효성분으로 포함하는 폐경기 증후군의 예방 또는 치료용 조성물 |
CN111655273B (zh) * | 2017-10-27 | 2022-11-25 | 天然恩朵技术株式会社 | 抗氧化、抗炎或用于抑制破骨细胞分化的组合物 |
KR102501311B1 (ko) * | 2020-06-05 | 2023-02-21 | (주)내츄럴엔도텍 | 피로 회복용 조성물 |
KR102609296B1 (ko) | 2021-01-15 | 2023-12-05 | 한국식품연구원 | 백수오 유래 다당 분획물을 유효성분으로 함유하는 여성 갱년기 질환의 개선, 예방 또는 치료용 조성물 |
KR102501845B1 (ko) * | 2021-02-08 | 2023-02-20 | 경희대학교 산학협력단 | 백수오 추출물을 유효성분으로 포함하는 피부 재생 또는 상처 치료용 조성물 |
KR102651338B1 (ko) | 2023-12-28 | 2024-03-26 | 주식회사 상상바이오 | 여성의 에스트로겐 정상화용 식품 조성물 |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2002047702A1 (en) * | 2000-12-15 | 2002-06-20 | Naturalendo Tech Co., Ltd. | Compositions for inducing secretion of insulin-like growth factor-1 |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5597585A (en) * | 1995-12-26 | 1997-01-28 | Williams; Andrew H. | Vitamin/mineral composition |
KR19980061480A (ko) * | 1996-12-31 | 1998-10-07 | 이웅열 | 생약과 비타민 k를 함유하는 골다공증 치료제 |
KR100374416B1 (ko) * | 2000-11-14 | 2003-03-04 | 노용일 | 고지혈증 및 협심증 예방 및 치료용 생약조성물 |
KR20030022655A (ko) * | 2001-09-10 | 2003-03-17 | (주)내츄럴엔도텍 | Igf-1 분비를 유도하는 약제학적 조성물 및 건강식품 |
KR100586813B1 (ko) * | 2001-10-10 | 2006-06-08 | 한국 한의학 연구원 | 혼합 생약재 추출물 및 이를 포함하는 골다공증 예방 또는 치료용 건강식품 |
KR100540033B1 (ko) * | 2002-01-18 | 2005-12-29 | 주식회사 팬제노믹스 | 관절염 치료용 생약 조성물 및 그 제조방법 |
-
2002
- 2002-08-06 KR KR1020020046327A patent/KR100382040B1/ko active IP Right Review Request
-
2003
- 2003-08-06 WO PCT/KR2003/001574 patent/WO2004012754A1/en active Application Filing
- 2003-08-06 JP JP2004525869A patent/JP4820548B2/ja not_active Expired - Lifetime
- 2003-08-06 US US10/523,645 patent/US20060051433A1/en not_active Abandoned
- 2003-08-06 AU AU2003251185A patent/AU2003251185A1/en not_active Abandoned
-
2006
- 2006-03-31 US US11/393,952 patent/US7763284B2/en not_active Expired - Lifetime
-
2007
- 2007-08-07 US US11/834,953 patent/US20070269538A1/en not_active Abandoned
-
2011
- 2011-06-07 JP JP2011127661A patent/JP2011244819A/ja active Pending
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2002047702A1 (en) * | 2000-12-15 | 2002-06-20 | Naturalendo Tech Co., Ltd. | Compositions for inducing secretion of insulin-like growth factor-1 |
Also Published As
Publication number | Publication date |
---|---|
US20070269538A1 (en) | 2007-11-22 |
US20060051433A1 (en) | 2006-03-09 |
JP2005539007A (ja) | 2005-12-22 |
WO2004012754A1 (en) | 2004-02-12 |
KR100382040B1 (en) | 2003-04-26 |
US7763284B2 (en) | 2010-07-27 |
JP4820548B2 (ja) | 2011-11-24 |
US20060193929A1 (en) | 2006-08-31 |
AU2003251185A1 (en) | 2004-02-23 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP2011244819A (ja) | エストロゲン分泌促進及び女性生殖器組織細胞再生のための組成物 | |
RU2275930C2 (ru) | Композиция для коррекции возрастных изменений эндокринной системы человека (варианты) и способ получения фармацевтической формы на основе такой композиции | |
JP4892856B2 (ja) | 女性ホルモンバランス調整剤 | |
KR101563577B1 (ko) | 갱년기 여성의 에스트로겐 저하증의 개선 및 예방용 기능성 조성물 | |
CN1742993A (zh) | 治疗妇科疾病的中成药及其制备方法 | |
KR100585445B1 (ko) | 혼합 생약재를 이용한 골질환 예방 및 치료용 약제 조성물 | |
KR20170116948A (ko) | 당귀, 천궁 및 육계를 유효성분으로 함유하는 갱년기 증상의 개선을 위한 조성물 | |
KR101141194B1 (ko) | 폐경기 증상의 예방 또는 치료용 식물성에스트로겐 조성물 | |
KR101087608B1 (ko) | 갱년기 또는 폐경기 증상의 예방 또는 완화용 식물성에스트로겐 조성물 | |
KR101600751B1 (ko) | 녹용을 함유하는 여성 불임증 치료용 한약 조성물 제조 방법 | |
CN102048841B (zh) | 一种具有催乳作用的中药组合物及其制备工艺 | |
CN102048890B (zh) | 一种具有催乳作用的中药组合物及其制备方法 | |
CN101564465B (zh) | 一种用于养血益气、调经温寒的中药组合物及其制备方法 | |
CN101618087B (zh) | 一种具有改善更年期功能的保健食品 | |
CN113952419B (zh) | 一种用于慢性肾功能衰竭的药物组合物及制备方法和应用 | |
CN102488740A (zh) | 一种鹰嘴豆芽提取物在防治雌激素缺失的药物的用途 | |
KR101822834B1 (ko) | 갱년기 증상 완화용 조성물 | |
KR101671502B1 (ko) | 피니톨, d-카이로-이노시톨, 또는 이들의 유사 화합물을 유효성분으로 포함하는 여성 갱년기 증상의 개선, 예방, 또는 치료용 조성물 | |
JP4892857B2 (ja) | 更年期症の予防又は改善剤 | |
US7556828B2 (en) | Pharmaceutical composition for treatment of BPH and preparation thereof | |
JPH0753394A (ja) | 性機能改善剤 | |
JP6838146B2 (ja) | ピニトール、d−カイロ−イノシトール、又はこれらの類似化合物を有効成分として含む、女性の更年期症状の改善、予防、又は治療用の組成物 | |
CN1285348C (zh) | 用于丰乳的组合物及其制备方法以及其用途 | |
Button et al. | Phytoestrogens for osteoporosis | |
CN1833682A (zh) | 一种治疗产后疾病的中药组合物 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20120727 |
|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20130122 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20130129 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20130424 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20130509 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20130529 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20130618 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20131008 |