WO2018123908A1 - Composition for inhibiting phosphodiesterase-5 activity - Google Patents
Composition for inhibiting phosphodiesterase-5 activity Download PDFInfo
- Publication number
- WO2018123908A1 WO2018123908A1 PCT/JP2017/046245 JP2017046245W WO2018123908A1 WO 2018123908 A1 WO2018123908 A1 WO 2018123908A1 JP 2017046245 W JP2017046245 W JP 2017046245W WO 2018123908 A1 WO2018123908 A1 WO 2018123908A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- genus
- composition according
- composition
- extract
- plant belonging
- Prior art date
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 64
- 230000000694 effects Effects 0.000 title claims abstract description 30
- 108010037581 Type 5 Cyclic Nucleotide Phosphodiesterases Proteins 0.000 title claims abstract description 29
- 102000011016 Type 5 Cyclic Nucleotide Phosphodiesterases Human genes 0.000 title claims abstract description 29
- 230000002401 inhibitory effect Effects 0.000 title claims abstract description 16
- 241000196324 Embryophyta Species 0.000 claims abstract description 68
- 241000266331 Eugenia Species 0.000 claims abstract description 12
- 241000350160 Haematoxylum Species 0.000 claims abstract description 8
- 241000219433 Myrica Species 0.000 claims abstract description 8
- 241001092459 Rubus Species 0.000 claims abstract description 8
- 241001289522 Fallopia Species 0.000 claims abstract description 5
- 241001092073 Filipendula Species 0.000 claims abstract description 5
- 241000532927 Lagerstroemia Species 0.000 claims abstract description 5
- 241001083505 Punica Species 0.000 claims abstract description 5
- 241001534869 Terminalia Species 0.000 claims abstract description 5
- 241000157352 Uncaria Species 0.000 claims abstract description 5
- 244000294611 Punica granatum Species 0.000 claims description 12
- 235000014360 Punica granatum Nutrition 0.000 claims description 11
- 235000011472 cat’s claw Nutrition 0.000 claims description 7
- 235000013305 food Nutrition 0.000 claims description 7
- 230000018052 penile erection Effects 0.000 claims description 7
- 208000002815 pulmonary hypertension Diseases 0.000 claims description 7
- 240000008620 Fagopyrum esculentum Species 0.000 claims description 6
- 235000009419 Fagopyrum esculentum Nutrition 0.000 claims description 6
- 244000274911 Myrica cerifera Species 0.000 claims description 6
- 235000009134 Myrica cerifera Nutrition 0.000 claims description 6
- 240000001341 Reynoutria japonica Species 0.000 claims description 6
- 241001451111 Fragaria vesca subsp. americana Species 0.000 claims description 5
- 235000018167 Reynoutria japonica Nutrition 0.000 claims description 5
- 244000269457 Rubus rugosus Species 0.000 claims description 5
- 244000223014 Syzygium aromaticum Species 0.000 claims description 5
- 230000004064 dysfunction Effects 0.000 claims description 5
- 210000001635 urinary tract Anatomy 0.000 claims description 5
- 235000014138 Caesalpinia decapetala Nutrition 0.000 claims description 4
- 240000009088 Fragaria x ananassa Species 0.000 claims description 4
- 235000003623 Rubus rugosus Nutrition 0.000 claims description 4
- 235000016639 Syzygium aromaticum Nutrition 0.000 claims description 4
- 235000009330 Terminalia Nutrition 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 claims description 3
- 235000016622 Filipendula ulmaria Nutrition 0.000 claims description 3
- 244000308505 Filipendula ulmaria Species 0.000 claims description 3
- 240000000161 Lagerstroemia indica Species 0.000 claims description 3
- 235000000283 Lagerstroemia parviflora Nutrition 0.000 claims description 3
- 244000198896 Lagerstroemia speciosa Species 0.000 claims description 3
- 208000004403 Prostatic Hyperplasia Diseases 0.000 claims description 3
- 241001600036 Rubus armeniacus Species 0.000 claims description 3
- 244000172730 Rubus fruticosus Species 0.000 claims description 3
- 235000017848 Rubus fruticosus Nutrition 0.000 claims description 3
- 241000609854 Rubus idaeus subsp. strigosus Species 0.000 claims description 3
- 235000010779 Rubus strigosus Nutrition 0.000 claims description 3
- 244000191422 Terminalia bellirica Species 0.000 claims description 3
- 235000012023 Terminalia bellirica Nutrition 0.000 claims description 3
- 235000009319 Terminalia catappa Nutrition 0.000 claims description 3
- 244000277583 Terminalia catappa Species 0.000 claims description 3
- 241000683228 Uncaria guianensis Species 0.000 claims description 3
- 230000002265 prevention Effects 0.000 claims description 3
- 201000004240 prostatic hypertrophy Diseases 0.000 claims description 3
- 241000222350 Pleurotus Species 0.000 claims description 2
- 240000005020 Acaciella glauca Species 0.000 claims 2
- 235000003499 redwood Nutrition 0.000 claims 2
- 235000021012 strawberries Nutrition 0.000 claims 1
- 102100029175 cGMP-specific 3',5'-cyclic phosphodiesterase Human genes 0.000 abstract description 3
- 101100189582 Dictyostelium discoideum pdeD gene Proteins 0.000 abstract 1
- 101150098694 PDE5A gene Proteins 0.000 abstract 1
- 239000000284 extract Substances 0.000 description 74
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 42
- 239000000047 product Substances 0.000 description 42
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 31
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 24
- 238000000605 extraction Methods 0.000 description 16
- 238000000034 method Methods 0.000 description 16
- 239000000843 powder Substances 0.000 description 15
- 239000000706 filtrate Substances 0.000 description 14
- 238000001914 filtration Methods 0.000 description 13
- 238000011282 treatment Methods 0.000 description 13
- ZOOGRGPOEVQQDX-UUOKFMHZSA-N 3',5'-cyclic GMP Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-UUOKFMHZSA-N 0.000 description 12
- 241000234314 Zingiber Species 0.000 description 12
- 235000006886 Zingiber officinale Nutrition 0.000 description 12
- 235000008397 ginger Nutrition 0.000 description 12
- 235000013399 edible fruits Nutrition 0.000 description 11
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 10
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 10
- 238000004108 freeze drying Methods 0.000 description 10
- 239000002904 solvent Substances 0.000 description 10
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 8
- 238000012360 testing method Methods 0.000 description 8
- 230000017531 blood circulation Effects 0.000 description 7
- 241001465754 Metazoa Species 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- 241000700159 Rattus Species 0.000 description 6
- 238000001035 drying Methods 0.000 description 6
- 210000002307 prostate Anatomy 0.000 description 6
- 239000002994 raw material Substances 0.000 description 6
- 239000003826 tablet Substances 0.000 description 6
- 235000003840 Amygdalus nana Nutrition 0.000 description 5
- 244000296825 Amygdalus nana Species 0.000 description 5
- 235000011432 Prunus Nutrition 0.000 description 5
- 230000003222 cGMP degradation Effects 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 238000005259 measurement Methods 0.000 description 5
- 235000014774 prunus Nutrition 0.000 description 5
- 229940058015 1,3-butylene glycol Drugs 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- 150000001298 alcohols Chemical class 0.000 description 4
- 235000019437 butane-1,3-diol Nutrition 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 230000008338 local blood flow Effects 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 238000000638 solvent extraction Methods 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 235000016623 Fragaria vesca Nutrition 0.000 description 3
- 235000011363 Fragaria x ananassa Nutrition 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 239000012153 distilled water Substances 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 239000000419 plant extract Substances 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 239000012488 sample solution Substances 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 210000002460 smooth muscle Anatomy 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 2
- 241000282472 Canis lupus familiaris Species 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 241000700198 Cavia Species 0.000 description 2
- 241000282693 Cercopithecidae Species 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- IVOMOUWHDPKRLL-KQYNXXCUSA-N Cyclic adenosine monophosphate Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 238000008157 ELISA kit Methods 0.000 description 2
- 235000013420 Eugenia uniflora Nutrition 0.000 description 2
- 240000003813 Eugenia uniflora Species 0.000 description 2
- 240000007829 Haematoxylum campechianum Species 0.000 description 2
- 101000988412 Homo sapiens cGMP-specific 3',5'-cyclic phosphodiesterase Proteins 0.000 description 2
- 206010020880 Hypertrophy Diseases 0.000 description 2
- 241000207923 Lamiaceae Species 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 229940123333 Phosphodiesterase 5 inhibitor Drugs 0.000 description 2
- 235000004789 Rosa xanthina Nutrition 0.000 description 2
- 241000220222 Rosaceae Species 0.000 description 2
- 235000011034 Rubus glaucus Nutrition 0.000 description 2
- 244000235659 Rubus idaeus Species 0.000 description 2
- 235000009122 Rubus idaeus Nutrition 0.000 description 2
- IVOMOUWHDPKRLL-UHFFFAOYSA-N UNPD107823 Natural products O1C2COP(O)(=O)OC2C(O)C1N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-UHFFFAOYSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 229940095074 cyclic amp Drugs 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 235000011869 dried fruits Nutrition 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003623 enhancer Substances 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 238000002875 fluorescence polarization Methods 0.000 description 2
- 235000013376 functional food Nutrition 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 239000002590 phosphodiesterase V inhibitor Substances 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 238000010298 pulverizing process Methods 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 238000001179 sorption measurement Methods 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 150000005846 sugar alcohols Polymers 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- RQFCJASXJCIDSX-UHFFFAOYSA-N 14C-Guanosin-5'-monophosphat Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(COP(O)(O)=O)C(O)C1O RQFCJASXJCIDSX-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
- 244000215068 Acacia senegal Species 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 241000195940 Bryophyta Species 0.000 description 1
- 241000220398 Cherax communis Species 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 235000005903 Dioscorea Nutrition 0.000 description 1
- 244000281702 Dioscorea villosa Species 0.000 description 1
- 235000000504 Dioscorea villosa Nutrition 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 239000004606 Fillers/Extenders Substances 0.000 description 1
- 240000004670 Glycyrrhiza echinata Species 0.000 description 1
- 235000001453 Glycyrrhiza echinata Nutrition 0.000 description 1
- 235000006200 Glycyrrhiza glabra Nutrition 0.000 description 1
- 235000017382 Glycyrrhiza lepidota Nutrition 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 244000132436 Myrica rubra Species 0.000 description 1
- 241000219926 Myrtaceae Species 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 241001107098 Rubiaceae Species 0.000 description 1
- 241001092387 Spiraea Species 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 239000003463 adsorbent Substances 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 238000007605 air drying Methods 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 230000004872 arterial blood pressure Effects 0.000 description 1
- 239000012131 assay buffer Substances 0.000 description 1
- 238000003149 assay kit Methods 0.000 description 1
- 235000013361 beverage Nutrition 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000002826 coolant Substances 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 210000005226 corpus cavernosum Anatomy 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- ZOOGRGPOEVQQDX-UHFFFAOYSA-N cyclic GMP Natural products O1C2COP(O)(=O)OC2C(O)C1N1C=NC2=C1NC(N)=NC2=O ZOOGRGPOEVQQDX-UHFFFAOYSA-N 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 235000004879 dioscorea Nutrition 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 239000002662 enteric coated tablet Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000002481 ethanol extraction Methods 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000007941 film coated tablet Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 235000012041 food component Nutrition 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 229940068517 fruit extracts Drugs 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 238000002523 gelfiltration Methods 0.000 description 1
- 239000003349 gelling agent Substances 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- RQFCJASXJCIDSX-UUOKFMHZSA-N guanosine 5'-monophosphate Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H]1O RQFCJASXJCIDSX-UUOKFMHZSA-N 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 238000007602 hot air drying Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 229940010454 licorice Drugs 0.000 description 1
- 229940069445 licorice extract Drugs 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 230000027939 micturition Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 235000011929 mousse Nutrition 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 239000003002 pH adjusting agent Substances 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 210000003899 penis Anatomy 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 210000001147 pulmonary artery Anatomy 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 229960002639 sildenafil citrate Drugs 0.000 description 1
- DEIYFTQMQPDXOT-UHFFFAOYSA-N sildenafil citrate Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O.CCCC1=NN(C)C(C(N2)=O)=C1N=C2C(C(=CC=1)OCC)=CC=1S(=O)(=O)N1CCN(C)CC1 DEIYFTQMQPDXOT-UHFFFAOYSA-N 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 235000015096 spirit Nutrition 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000007940 sugar coated tablet Substances 0.000 description 1
- 238000000194 supercritical-fluid extraction Methods 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 210000003708 urethra Anatomy 0.000 description 1
- 230000002485 urinary effect Effects 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 238000009777 vacuum freeze-drying Methods 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 235000001459 whitebark Nutrition 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K10/00—Animal feeding-stuffs
- A23K10/30—Animal feeding-stuffs from material of plant origin, e.g. roots, seeds or hay; from material of fungal origin, e.g. mushrooms
-
- 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
- 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)
-
- 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)
- A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
-
- 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)
- A61K36/61—Myrtaceae (Myrtle family), e.g. teatree or eucalyptus
-
- 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)
- A61K36/70—Polygonaceae (Buckwheat family), e.g. spineflower or dock
-
- 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)
- A61K36/73—Rosaceae (Rose family), e.g. strawberry, chokeberry, blackberry, pear or firethorn
-
- 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)
- A61K36/74—Rubiaceae (Madder family)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- 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
-
- 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
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
-
- 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
- A61P13/08—Drugs for disorders of the urinary system of the prostate
-
- 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
- A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
-
- 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
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
Definitions
- the present invention relates to a composition for inhibiting phosphodiesterase 5 activity.
- Phosphodiesterase is an enzyme that hydrolyzes cyclic GMP (cGMP) and cyclic AMP (cAMP), and there are multiple families in mammals.
- phosphodiesterase 5 (PDE5) is mainly involved in cGMP degradation.
- cGMP acts as an intracellular second messenger, relaxes smooth muscle and increases blood flow. For this reason, by suppressing the activity of PDE5, smooth muscle relaxes and blood flow increases.
- PDE5 inhibitors are known as drugs that utilize this action, and typical drugs such as sildenafil citrate are known.
- PDE5 inhibitor inhibits the activity of PDE5, suppresses cGMP degradation, and increases local blood flow to improve symptoms such as reduced penile erection ability, bladder and prostate function, and pulmonary hypertension It is utilized as.
- Patent Document 1 black ginger can inhibit the activity of PDE.
- An object of the present invention is to provide a new composition capable of inhibiting the activity of PDE5.
- the present inventors have conducted extensive studies in view of the above problems, and as a result, the following plants: Rubus, Punica, Filipendula, Myrica, Eugenia. ), Lagerstroemia, Terminalia, Haematoxylon, Fallopia or Uncaria, it has been found that the activity of PDE5 can be inhibited.
- the present invention has been completed as a result of further studies based on this finding, and is as follows. Item 1.
- compositions for inhibiting phosphodiesterase 5 activity comprising a processed product of at least one plant selected from the group consisting of (Fallopia) and Uncaria.
- Item 2. The composition according to Item 1, wherein the plant belonging to the genus Rubus is at least one selected from the group consisting of Himalayan blackberry (Rubus armeniacus Focke), Aedesian strawberry (Rubus fruticosus), and American strawberry (Rubus strigosus). .
- composition according to Item 1 wherein the plant belonging to the genus Pomegranate is pomegranate (Punica granatum).
- Item 4. Item 2. The composition according to Item 1, wherein the plant belonging to the genus Pleurotus is Filipendula ulmaria.
- Item 5. Item 2. The composition according to Item 1, wherein the plant belonging to the genus Corpus is at least one selected from the group consisting of Myrica cerifera and Myrica rubura.
- the composition according to Item 1, wherein the plant belonging to the genus Eugenia is at least one selected from the group consisting of Eugenia uniflora and clove (Eugenia aromaticum).
- Item 7. Item 2.
- composition according to Item 1 wherein the plant belonging to the genus Crape myrtle is banaba (Lagerstroemia speciosa).
- Item 8. Item 2. The composition according to Item 1, wherein the plant belonging to the genus Momotamana is at least one selected from the group consisting of Terminalia catappa and Terminalia bellirica.
- Item 9. Item 2. The composition according to Item 1, wherein the plant belonging to the genus Akaminoki is Haematoxylon campechianum.
- Item 11. Item 2.
- composition according to Item 1 wherein the plant belonging to the genus Kasakazura is Uncaria guianensis.
- Item 12. Item 12. The composition according to any one of Items 1 to 11, which is for prevention or amelioration selected from the group consisting of penile erection function, lower urinary tract dysfunction, prostate hypertrophy and pulmonary hypertension.
- Item 13. Item 13. The composition according to any one of Items 1 to 12, which is a food composition, a pharmaceutical composition, or a feed composition.
- the activity of PDE5 can be inhibited. Therefore, the composition of the present invention is used for the purpose of preventing or ameliorating diseases caused by decreased blood flow accompanying cGMP degradation such as penile erection function, lower urinary tract dysfunction, prostatic hypertrophy, and pulmonary hypertension. can do.
- diseases caused by decreased blood flow accompanying cGMP degradation such as penile erection function, lower urinary tract dysfunction, prostatic hypertrophy, and pulmonary hypertension. can do.
- the present invention relates to the genus Rubus, Punica, Filipendula, Myrica, Eugenia, Lagerstroemia, Terminalia, and Haematoxylon. ), A composition for inhibiting phosphodiesterase 5 activity, comprising a processed product of at least one plant selected from the group consisting of Fallopia and Uncaria.
- the genus Raspberry As raw materials for the processed plant products contained as an active ingredient in the composition of the present invention, the genus Raspberry, Pomegranate, Prunus spp., Prunus genus, Eugenia, Prunus spp., Prunus spp. Plants belonging to any of the genera can be mentioned.
- the genus Rubus belongs to the family Rosaceae and is not intended to limit the present invention. Examples of plants belonging to the genus include Himalayan blackberry (Rubus armeniacus Focke), Yabu strawberry (Rubus fruticosus), American strawberry (Rubus strigosus), etc. Is done.
- the pomegranate belongs to the family Lamiaceae and does not limit the present invention, but examples of plants belonging to the genus include pomegranate (Punica granatum).
- the genus Spiraea belongs to the family Rosaceae and does not limit the present invention, but examples of plants belonging to the genus include Filipendula ulmaria.
- the genus genus belongs to the genus Dioscorea and does not limit the present invention, but examples of plants belonging to the genus include white licorice (Myrica cerifera), bayberry (Myrica rubura) and the like.
- the genus Eugenia belongs to the Myrtaceae family and does not limit the present invention, but examples of plants belonging to the genus include Eugenia uniflora and clove (Eugenia aromaticum).
- the genus Crapery belongs to the family Lamiaceae and does not limit the present invention
- examples of plants belonging to the genus include banaba (Lagerstroemia speciosa) and the like.
- Momotamana belongs to the family Cypridaceae and does not limit the present invention
- examples of plants belonging to the genus include Momotamana (Terminalia catappa), Seitamirobaran (Terminalia bellirica) and the like.
- the genus Akaminoki belongs to the leguminous family and does not limit the present invention, but examples of plants belonging to the genus include Akaminoki (Haematoxylon campechianum) and the like.
- the buckwheat genus belongs to the family Taceae and does not limit the present invention, but examples of plants belonging to the genus include Fallopia japonica.
- the genus Kakazura belongs to the Rubiaceae family and does not limit the present invention, but examples of plants belonging to the genus include cats claw (Uncaria guianensis).
- the site of use is not particularly limited as long as these plants are used, but examples include leaves, stems, fruits, flowers, buds, branches, stems, bark, roots, florets, seeds, seed coats, and the like, which are appropriately selected according to each plant. That's fine.
- leaves in the genus Raspberry fruits, fruits in the genus Pomegranate, leaves in the genus Prunus, stems, bark in the genus Genus, Eugenia In the genus, fruit, floret, crape myrtle leaves, momotamana genus fruit, red crested genus stem, buckwheat genus stem, leaf, and genus Kazura genus root, stem, leaf.
- one kind may be used alone, or two or more kinds may be used in combination.
- the plant processed product includes a pulverized product, a dried product, and an extract of the plant as the raw material.
- the pulverized product is not particularly limited as long as the plant is pulverized by a pulverizer known in the art such as a jet mill.
- the dried product is not particularly limited as long as the plant is dried, and is obtained according to a conventionally known drying method such as sun drying, far-infrared irradiation, dryer (hot air drying, cold air drying, vacuum freeze drying, etc.) and the like. be able to.
- the water content in the dried product is preferably 10% by weight or less, and more preferably 8% by weight or less.
- the form of the dried product is not limited, and any of a dried product of the plant itself and a pulverized product of the dried product may be used.
- the dried pulverized product can be obtained by pulverizing the dried product according to the same method as the pulverized product.
- what was obtained by drying after making the plant used as a raw material a fermentation process or an enzyme process as a dried material can also be used.
- Extract production method extraction method
- extraction conditions and the like are not particularly limited, and may be a conventionally known method.
- the plant can be cut, crushed or dried as necessary, and then extracted by extraction or solvent extraction.
- solvent extraction a known method in this field may be employed.
- a conventionally known extraction method such as water (including warm water and hot water) extraction, alcohol extraction, supercritical extraction, or the like can be used. .
- the solvent is, for example, water; alcohols such as lower alcohols such as methanol, ethanol and isopropanol, and polyhydric alcohols such as propylene glycol and 1,3-butylene glycol (anhydrous, regardless of water content). ); Ketones such as acetone, esters such as diethyl ether, dioxane, acetonitrile, and ethyl acetate, xylene, benzene, chloroform, and the like.
- the solvent is preferably water, lower alcohol, 1,3-butylene glycol or the like, more preferably water, methanol, ethanol or 1,3-butylene glycol, and still more preferably water, methanol or hydrous ethanol. These solvents may be used alone or in combination of two or more.
- the extract obtained through the solvent extraction in this way can be particularly referred to as a solvent extract.
- a solvent extract when water is used as a solvent, a water extract, when a lower alcohol is used, a lower alcohol extract, when ethanol is used, an ethanol extraction is used. It can be called a thing etc.
- the obtained extract may be used as it is, or may be dried and used in a solid state such as powder or granule.
- the obtained extract may be subjected to purification, concentration treatment, separation treatment of highly active fraction, and the like as necessary.
- processing such as filtration, adsorption
- concentration treatment a conventional method such as an evaporator can be used.
- known separation treatments such as gel filtration, adsorption treatment, silica gel column chromatography, HPLC (High performance liquid chromatography) and the like can be used.
- a method of subjecting the extract obtained as described above (and its dried product, purified product, concentrated product, and highly active fraction) to lyophilization and pulverization if necessary.
- an extract such as dextrin, corn starch, gum arabic and the like may be added and powdered according to a conventionally known method such as a method of powdering by spray drying, and the extract used in the present invention may be used.
- the extract may be used by dissolving it in water, ethanol or the like, if necessary.
- the plant extract is preferably an extract obtained by drying, crushing and / or cutting a plant (use site) as a raw material, and extracting and filtering using a suitable solvent.
- the extract obtained by further drying the obtained extract is illustrated.
- the present invention is not limited, and a person skilled in the art may appropriately extract according to each plant or use site.
- the extract is 100 g of a plant as a raw material, more preferably a dried product or a crushed product of the plant.
- / or the cut material is immersed in 1 to 50 liters of extraction solvent per 100 g and at any temperature (for example, 15 to 90 ° C.) with stirring as necessary for any time (for example, 10 minutes to 24 hours). ) Extraction, followed by filtration.
- a plant extract (including a dried product thereof) is preferably used as a processed plant product.
- the processed plant product used in the present invention may be a commercially available product, or may be a product obtained by appropriately subjecting the commercially available product to a treatment such as drying.
- the plant processed product thus obtained may be used alone or in combination of two or more.
- the content of the processed plant product in the composition of the present invention is not limited as long as the processed plant product is contained in the composition, and the effect of the present invention is obtained.
- the processed product of the plant is contained in an amount of more than 0% by weight, preferably more than 0% by weight and less than 100% by weight, more preferably in terms of dry matter. Is exemplified by 0.001 to 99% by weight. When two or more kinds of workpieces are used, the total amount satisfies the value.
- a dried product is obtained by freeze-drying the processed product. The freeze-drying process is performed by vacuum concentration using a general evaporator and freeze-drying in a vacuum state. A more detailed processing procedure follows an embodiment described later.
- the administration (intake) amount of the processed plant product is not particularly limited as long as the effect of the present invention is exhibited, and the physique, age, symptom, application of the subject (target animal) What is necessary is just to set suitably according to a form, the intended purpose, the grade of the effect expected, etc.
- a daily administration (intake) amount the processed product of the plant is a total amount (in terms of dry weight), preferably 0.001 to 8000 mg, based on an adult with a body weight of 60 kg. More preferably, 0.01 to 5000 mg is exemplified.
- the composition of the present invention may be single dose (intake) or multiple dose (intake) per day.
- the composition of the present invention may be oral or parenteral.
- the form of the composition of the present invention is not limited, and may be appropriately set depending on the purpose.
- liquid forms such as liquids, emulsions, suspensions, syrups, extracts, spirits, elixirs, powders, granules, fine granules, tablets, pills, capsules ( (Including hard capsules and soft capsules), troches, chewables, gels, creams, pastes, mousses, sheets, semi-solid or solid forms such as lyophilizates in liquid form, in addition, aerosols and other patches,
- Various forms such as a haptic agent and a transdermal absorption preparation are exemplified.
- the composition of the present invention when it is in a solid form, it may be used by mixing with water or the like, and the composition of the present invention may be in a sustained-release dosage form.
- the tablet can be a tablet with a conventionally known coating, such as a sugar-coated tablet, a gelatin-encapsulated tablet, an enteric-coated tablet, a film-coated tablet, a double tablet, or a multilayer tablet, if necessary. .
- the use mode of the composition of the present invention is not limited, and may be appropriately set according to the purpose.
- Examples of usage of the composition of the present invention include food compositions (including beverages, health functional foods (including foods for specified health use, nutritional functional foods, functional display foods, supplements, etc.), foods for the sick, It can be used as an additive to pharmaceutical compositions, feed compositions, food compositions, pharmaceutical compositions, feeds, and the like.
- composition of the present invention may be produced according to conventionally known ordinary procedures in the above-mentioned various forms, usage modes, etc., and if necessary, pharmaceutically acceptable ingredients, cosmetically acceptable ingredients. What is necessary is just to mix and manufacture with arbitrary components, such as an edible component.
- Solvents water, lower alcohols such as methanol, ethanol and isopropanol, alcohols such as polyhydric alcohols such as propylene glycol and 1,3-butylene glycol (anhydrous, regardless of water content), etc.
- Excipients disintegrants, diluents, lubricants, flavors, colorants, sweeteners, flavoring agents, suspending agents, wetting agents, emulsifiers, solubilizers, dispersants, buffers, binders, penetration enhancers Agent, stabilizer, extender, preservative, thickener, pH adjuster, surfactant, coating agent, absorption enhancer, adsorbent, filler, antioxidant, anti-inflammatory agent, cooling agent, film-forming agent And gelling agents, amino acids, vitamins, enzymes, various nutritional components, and the like. These may be used alone or in combination of two or more.
- the subject (target animal) of the composition is not limited, but humans and mammals other than humans are exemplified.
- mammals other than humans include animals in which phosphodiesterase 5 promotes the degradation of cGMP, and animals such as mice, rats, guinea pigs, rabbits, dogs, cats, monkeys, pigs, cows, horses, preferably mice. And animals such as rats, guinea pigs, rabbits, dogs and monkeys.
- the activity of phosphodiesterase 5 can be inhibited using the processed plant product as an active ingredient.
- this invention provides the manufacturing method of the composition for PDE5 activity inhibition characterized by using the processed material of the said plant.
- this invention provides the manufacturing method of the composition for PDE5 activity inhibition containing the process of preparing the processed material of the said plant.
- this invention provides the PDE5 activity inhibition method characterized by using the processed material of the said plant.
- the activity of PDE5 can be inhibited. Therefore, according to the present invention, the degradation of cGMP can be suppressed, and the composition of the present invention can be used for the purpose of preventing or ameliorating diseases caused by PDE5 activity and local blood flow reduction.
- the composition of the present invention is useful for the prevention or improvement of penile erection function, lower urinary tract dysfunction, prostatic hypertrophy, pulmonary hypertension, etc., although the present invention is not limited thereto.
- smooth muscle is relaxed by the PDE5 inhibitory action, thereby improving the penile erection function by increasing the blood flow to the cavernous corpus cavernosum, and lowering the lower urine by increasing the blood flow to the urinary system
- Can improve tract obstruction can increase prostate blood flow in the prostate and urethra, can alleviate prostate enlargement, and can increase blood flow to the lung tissue to reduce pulmonary artery pressure it can.
- composition of the present invention can also be preferably applied to subjects who are concerned about male function, subjects who are concerned about urination function, and the like.
- composition of the present invention includes PDE5 activity inhibitor, penile erection function (deficiency) treatment, lower urinary tract dysfunction treatment, prostate hypertrophy treatment, pulmonary hypertension treatment (particularly pulmonary arterial pulmonary hypertension), etc. Can also be used as
- Test example 1 Processed Plants Extracts of each plant were prepared using the plants shown in Table 1 as raw materials. Specifically, for Examples 1, 5, 9 and 10, extracts were prepared according to the following procedure, and commercially available products were used for the other examples.
- Example 1 Himalayan Blackberry Himalayan Blackberry leaves 50 g were crushed, 1000 ml of water was added, and extraction treatment was performed at 80 ° C. for 1 hour. The obtained extract was filtered through Miracloth (manufactured by Merck Millipore), and the filtrate from which insoluble components had been removed was freeze-dried to obtain a Himalayan blackberry extract (7.9 g of dried extract).
- Example 2 Yab Strawberry An extract of Yab Strawberry (special order made by Nippon Shinyaku Co., Ltd., dry powder) was used. This extract was obtained by crushing dried yab strawberry leaves, extracting with methanol, filtering the resulting extract, and lyophilizing the filtrate from which insoluble components had been removed. is there.
- Example 3 American Strawberry American strawberry leaf and fruit extracts (made by Nippon Shinyaku Co., Ltd., dry powder) were used. This extract was obtained by crushing a dried product of American strawberry leaves and fruits, extracting by adding methanol, filtering the resulting extract, and lyophilizing the filtrate from which insoluble components had been removed. It is.
- Example 4 pericarp extract of pomegranate pomegranate (trade name pomegranate rind extract powder, Koei Kogyo Co., Ltd., powder dry matter) was used.
- Example 5 40 g of dried stems and leaves of C. communis was crushed, 1000 ml of water was added, and extraction was performed at 80 ° C. for 1 hour. The obtained extract was filtered with Miracloth (manufactured by Merck Millipore), and the filtrate from which insoluble components had been removed was freeze-dried to obtain a licorice extract (9.9 g of dried extract).
- Example 6 An extract of bark of white bayberry (special order made by Nippon Shinyaku Co., Ltd., dry powder) was used. This extract was obtained by crushing a dried white bark bark, adding methanol for extraction, filtering the resulting extract, and lyophilizing the filtrate from which insoluble components had been removed. .
- Example 7 An extract of bark of yamamomo yamamomo (special order made by Nippon Shinyaku Co., Ltd., dry powder) was used. This extract was obtained by crushing a dried product of bayberry bark, extracting by adding methanol, filtering the obtained extract, and lyophilizing the filtrate from which insoluble components were removed.
- Example 8 Tachibana adecta fruit extract (special order made by Nippon Shinyaku Co., Ltd., dry powder) was used. This extract was obtained by crushing the dried fruit of Tachibana adek, adding methanol for extraction, filtering the resulting extract, and freeze-drying the filtrate from which insoluble components had been removed. .
- Example 9 50 g of dried clove clove flower was crushed, 1000 ml of water was added, and extraction treatment was performed at 80 ° C. for 1 hour. The obtained extract was filtered with Miracloth (manufactured by Merck Millipore), and the filtrate from which insoluble components were removed was freeze-dried to obtain a clove extract (10.1 g of dried extract).
- Example 10 banaba banaba crushed dry matter 60g leaf (mass ratio of water and ethanol 1: 1) 50 wt% ethanol 900ml added to 25 ° C., was carried out extraction at 12 hours. The obtained extract was filtered through Miracloth (Merck Millipore), ethanol was distilled off from the filtrate from which insoluble components had been removed, and then freeze-dried to obtain a banaba extract (8.9 g dry extract). Obtained.
- Example 11 An extract of the fruit of Momota Mana Momota Mana (special order made by Nippon Shinyaku Co., Ltd., dry powder) was used. This extract was obtained by crushing a dried product of Momotamana fruit, adding methanol to perform extraction, filtering the obtained extract, and freeze-drying the filtrate from which insoluble components were removed.
- Example 12 Seitakamirobaran Fruit extract of Seitakamirobalan (special order made by Nippon Shinyaku Co., Ltd., dry powder) was used. This extract was obtained by crushing the dried fruit of Seitacamilobaran, adding methanol to extract it, filtering the resulting extract, and freeze-drying the filtrate from which insoluble components had been removed. is there.
- Example 13 haematoxylum campechianum stem extract of haematoxylum campechianum (Nippon Shinyaku Co. custom, powder dry matter) was used. This extract was obtained by crushing a dried stem of Akaminoki trunk, adding methanol for extraction, filtering the resulting extract, and freeze-drying the filtrate from which insoluble components had been removed.
- Example 14 Extracts of stems and leaves of Japanese knotweed weeds (special order made by Nippon Shinyaku Co., Ltd., dry powder) were used. This extract was obtained by crushing dried weedbird stems and leaves, extracting with methanol, filtering the resulting extract, and freeze-drying the filtrate from which insoluble components had been removed. is there.
- Example 15 Cats Claw Cats Claw root, stem and leaf extracts (made by Nippon Shinyaku Co., Ltd., dry powder) were used. This extract was obtained by crushing dried catscrow roots, stems and leaves, adding methanol to extract, filtering the resulting extract, and freeze-drying the filtrate from which insoluble components had been removed. It is a thing.
- Comparative Example An extract of rhizomes of black ginger black ginger (trade name: black ginger extract-P, manufactured by Oriza Oil Co., Ltd., dried powder) was used.
- Black ginger is a plant that is conventionally known to have an inhibitory action on phosphodiesterase (PDE).
- PDE5A Assay Kit # 60350 (manufactured by BPS Bioscience), 96-well plate, Pipetman, PerkinElmer EnVision 2102 Multilabel Reader (manufactured by PerkinElmer) was used to measure the inhibitory activity according to the instructions attached to the kit. did.
- Table 1 shows IC50 values.
- Test example 2 1. Measurement Procedure Using the extracts of Examples 1, 4, 5 and 10 prepared in the above test examples, the extract of the comparative example, and water as a control, the amount of cyclic guanosine monophosphate (cGMP) in rat tissue was measured. did.
- cGMP cyclic guanosine monophosphate
- the extract-containing administration liquid 500 mg / 2 mL / kg body weight
- the amount of cGMP in the penile tissue was measured according to the method described in cGMP ELISA kit.
- administration was carried out in the stomach in the same manner, and the amount of cGMP in the penile tissue was measured.
- the amount of cGMP at the time of administration of black ginger was slightly higher than the amount of cGMP at the time of administration of distilled water.
- the amount of cGMP at the time of administration of the extracts of Examples 1, 4, 5 and 10 was about twice or more than that at the time of administration of black ginger.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Botany (AREA)
- Mycology (AREA)
- Biotechnology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Microbiology (AREA)
- Medical Informatics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Alternative & Traditional Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Polymers & Plastics (AREA)
- Food Science & Technology (AREA)
- Urology & Nephrology (AREA)
- Zoology (AREA)
- Reproductive Health (AREA)
- Molecular Biology (AREA)
- Physiology (AREA)
- Animal Husbandry (AREA)
- Endocrinology (AREA)
- Gynecology & Obstetrics (AREA)
- Pulmonology (AREA)
- Nutrition Science (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Medicines Containing Plant Substances (AREA)
- Fodder In General (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
Abstract
[Problem] An objective of the present invention is to provide a novel composition that can inhibit the activity of PDE5. [Solution] A composition for inhibiting phosphodiesterase-5 activity, the composition comprising a processed product from at least one plant selected from the group consisting of Rubus, Punica, Filipendula, Myrica, Eugenia, Lagerstroemia, Terminalia, Haematoxylon, Fallopia and Uncaria.
Description
本発明は、ホスホジエステラーゼ５活性阻害用組成物に関する。
The present invention relates to a composition for inhibiting phosphodiesterase 5 activity.
ホスホジエステラーゼ（phosphodiesterase、ＰＤＥ）は、サイクリックＧＭＰ（ｃＧＭＰ）やサイクリックＡＭＰ（ｃＡＭＰ）を加水分解する酵素であり、哺乳動物では複数のファミリーが存在する。
Phosphodiesterase (PDE) is an enzyme that hydrolyzes cyclic GMP (cGMP) and cyclic AMP (cAMP), and there are multiple families in mammals.
このうち、ホスホジエステラーゼ５（ＰＤＥ５）は、主にｃＧＭＰの分解に関与する。ｃＧＭＰは、細胞内セカンドメッセンジャーとして作用し、平滑筋を弛緩させ、血流を増加させる。このため、ＰＤＥ５の活性を抑制することにより、平滑筋が弛緩し、血流が増加する。
Among these, phosphodiesterase 5 (PDE5) is mainly involved in cGMP degradation. cGMP acts as an intracellular second messenger, relaxes smooth muscle and increases blood flow. For this reason, by suppressing the activity of PDE5, smooth muscle relaxes and blood flow increases.
この作用を利用した薬剤として、今日、ＰＤＥ５阻害薬が知られており、代表的なものとしてシルデナフィルクエン酸塩を有効成分とする医薬品等が知られている。ＰＤＥ５阻害薬は、ＰＤＥ５の活性を阻害してｃＧＭＰの分解を抑制し、局所血流を増加させることにより、陰茎勃起能力の低下、膀胱や前立腺の機能低下、肺高血圧症といった症状の改善を目的として活用されている。
Today, PDE5 inhibitors are known as drugs that utilize this action, and typical drugs such as sildenafil citrate are known. PDE5 inhibitor inhibits the activity of PDE5, suppresses cGMP degradation, and increases local blood flow to improve symptoms such as reduced penile erection ability, bladder and prostate function, and pulmonary hypertension It is utilized as.
また、例えばクロショウガが、ＰＤＥの活性を阻害できることが知られている（特許文献１）。
For example, it is known that black ginger can inhibit the activity of PDE (Patent Document 1).
本発明は、ＰＤＥ５の活性を阻害できる新たな組成物を提供することを目的とする。
An object of the present invention is to provide a new composition capable of inhibiting the activity of PDE5.
本発明者らが前記課題に鑑み鋭意研究を重ねたところ、次の植物、すなわち、キイチゴ属（Rubus）、ザクロ属（Punica）、シモツケソウ属（Filipendula）、ヤマモモ属（Myrica）、エウゲニア属（Eugenia）、サルスベリ属（Lagerstroemia）、モモタマナ属（Terminalia）、アカミノキ属（Haematoxylon）、ソバカズラ属（Fallopia）またはカギカズラ属（Uncaria）に属する植物によれば、ＰＤＥ５の活性を阻害できることを見いだした。
本発明は該知見に基づき更に検討を重ねた結果完成されたものであり、次に掲げるものである。
項１．キイチゴ属（Rubus）、ザクロ属（Punica）、シモツケソウ属（Filipendula）、ヤマモモ属（Myrica）、エウゲニア属（Eugenia）、サルスベリ属（Lagerstroemia）、モモタマナ属（Terminalia）、アカミノキ属（Haematoxylon）、ソバカズラ属（Fallopia）及びカギカズラ属（Uncaria）からなる群より選択される少なくとも１つの植物の加工物を含有する、ホスホジエステラーゼ５活性阻害用組成物。
項２．キイチゴ属に属する植物が、ヒマラヤブラックベリー（Rubus armeniacus Focke）、セイヨウヤブイチゴ（Rubus fruticosus）及びアメリカイチゴ（Rubus strigosus）からなる群より選択される少なくとも１つである、項１に記載の組成物。
項３．ザクロ属に属する植物が、ザクロ（Punica granatum）である、項１に記載の組成物。
項４．シモツケソウ属に属する植物が、セイヨウナツユキソウ（Filipendula ulmaria）である、項１に記載の組成物。
項５．ヤマモモ属に属する植物が、シロコヤマモモ（Myrica cerifera）及びヤマモモ（Myrica rubura）からなる群より選択される少なくとも１つである、項１に記載の組成物。
項６．エウゲニア属に属する植物が、タチバナアデク（Eugenia uniflora）及びクローブ（Eugenia aromaticum）からなる群より選択される少なくとも１つである、項１に記載の組成物。
項７．サルスベリ属に属する植物が、バナバ（Lagerstroemia speciosa）である、項１に記載の組成物。
項８．モモタマナ属に属する植物が、モモタマナ（Terminalia catappa）及びセイタカミロバラン（Terminalia bellirica）からなる群より選択される少なくとも１つである、項１に記載の組成物。
項９．アカミノキ属に属する植物が、アカミノキ（Haematoxylon campechianum）である、項１に記載の組成物。
項１０．ソバカズラ属に属する植物が、イタドリ（Fallopia japonica）である、項１に記載の組成物。
項１１．カギカズラ属に属する植物が、キャッツクロー（Uncaria guianensis）である、項１に記載の組成物。
項１２．陰茎勃起機能、下部尿路機能障害、前立腺肥大及び肺高血圧症からなる群より選択される少なくとも１種の予防または改善用である、項１～１１のいずれかに記載の組成物。
項１３．食品組成物、医薬組成物または飼料組成物である、項１～１２のいずれかに記載の組成物。 The present inventors have conducted extensive studies in view of the above problems, and as a result, the following plants: Rubus, Punica, Filipendula, Myrica, Eugenia. ), Lagerstroemia, Terminalia, Haematoxylon, Fallopia or Uncaria, it has been found that the activity of PDE5 can be inhibited.
The present invention has been completed as a result of further studies based on this finding, and is as follows.
Item 1. Rubus, Punica, Filipendula, Myrica, Eugenia, Lagerstroemia, Momardana (Terminalia), Haematoxylon, Buckwheat A composition for inhibiting phosphodiesterase 5 activity, comprising a processed product of at least one plant selected from the group consisting of (Fallopia) and Uncaria.
Item 2. Item 2. The composition according to Item 1, wherein the plant belonging to the genus Rubus is at least one selected from the group consisting of Himalayan blackberry (Rubus armeniacus Focke), Aedesian strawberry (Rubus fruticosus), and American strawberry (Rubus strigosus). .
Item 3. Item 2. The composition according to Item 1, wherein the plant belonging to the genus Pomegranate is pomegranate (Punica granatum).
Item 4. Item 2. The composition according to Item 1, wherein the plant belonging to the genus Pleurotus is Filipendula ulmaria.
Item 5. Item 2. The composition according to Item 1, wherein the plant belonging to the genus Corpus is at least one selected from the group consisting of Myrica cerifera and Myrica rubura.
Item 6. Item 2. The composition according to Item 1, wherein the plant belonging to the genus Eugenia is at least one selected from the group consisting of Eugenia uniflora and clove (Eugenia aromaticum).
Item 7. Item 2. The composition according to Item 1, wherein the plant belonging to the genus Crape myrtle is banaba (Lagerstroemia speciosa).
Item 8. Item 2. The composition according to Item 1, wherein the plant belonging to the genus Momotamana is at least one selected from the group consisting of Terminalia catappa and Terminalia bellirica.
Item 9. Item 2. The composition according to Item 1, wherein the plant belonging to the genus Akaminoki is Haematoxylon campechianum.
Item 10. Item 2. The composition according to Item 1, wherein the plant belonging to the genus Buckwheat is a Japanese knotweed (Fallopia japonica).
Item 11. Item 2. The composition according to Item 1, wherein the plant belonging to the genus Kasakazura is Uncaria guianensis.
Item 12. Item 12. The composition according to any one of Items 1 to 11, which is for prevention or amelioration selected from the group consisting of penile erection function, lower urinary tract dysfunction, prostate hypertrophy and pulmonary hypertension.
Item 13. Item 13. The composition according to any one of Items 1 to 12, which is a food composition, a pharmaceutical composition, or a feed composition.
本発明は該知見に基づき更に検討を重ねた結果完成されたものであり、次に掲げるものである。
項１．キイチゴ属（Rubus）、ザクロ属（Punica）、シモツケソウ属（Filipendula）、ヤマモモ属（Myrica）、エウゲニア属（Eugenia）、サルスベリ属（Lagerstroemia）、モモタマナ属（Terminalia）、アカミノキ属（Haematoxylon）、ソバカズラ属（Fallopia）及びカギカズラ属（Uncaria）からなる群より選択される少なくとも１つの植物の加工物を含有する、ホスホジエステラーゼ５活性阻害用組成物。
項２．キイチゴ属に属する植物が、ヒマラヤブラックベリー（Rubus armeniacus Focke）、セイヨウヤブイチゴ（Rubus fruticosus）及びアメリカイチゴ（Rubus strigosus）からなる群より選択される少なくとも１つである、項１に記載の組成物。
項３．ザクロ属に属する植物が、ザクロ（Punica granatum）である、項１に記載の組成物。
項４．シモツケソウ属に属する植物が、セイヨウナツユキソウ（Filipendula ulmaria）である、項１に記載の組成物。
項５．ヤマモモ属に属する植物が、シロコヤマモモ（Myrica cerifera）及びヤマモモ（Myrica rubura）からなる群より選択される少なくとも１つである、項１に記載の組成物。
項６．エウゲニア属に属する植物が、タチバナアデク（Eugenia uniflora）及びクローブ（Eugenia aromaticum）からなる群より選択される少なくとも１つである、項１に記載の組成物。
項７．サルスベリ属に属する植物が、バナバ（Lagerstroemia speciosa）である、項１に記載の組成物。
項８．モモタマナ属に属する植物が、モモタマナ（Terminalia catappa）及びセイタカミロバラン（Terminalia bellirica）からなる群より選択される少なくとも１つである、項１に記載の組成物。
項９．アカミノキ属に属する植物が、アカミノキ（Haematoxylon campechianum）である、項１に記載の組成物。
項１０．ソバカズラ属に属する植物が、イタドリ（Fallopia japonica）である、項１に記載の組成物。
項１１．カギカズラ属に属する植物が、キャッツクロー（Uncaria guianensis）である、項１に記載の組成物。
項１２．陰茎勃起機能、下部尿路機能障害、前立腺肥大及び肺高血圧症からなる群より選択される少なくとも１種の予防または改善用である、項１～１１のいずれかに記載の組成物。
項１３．食品組成物、医薬組成物または飼料組成物である、項１～１２のいずれかに記載の組成物。 The present inventors have conducted extensive studies in view of the above problems, and as a result, the following plants: Rubus, Punica, Filipendula, Myrica, Eugenia. ), Lagerstroemia, Terminalia, Haematoxylon, Fallopia or Uncaria, it has been found that the activity of PDE5 can be inhibited.
The present invention has been completed as a result of further studies based on this finding, and is as follows.
Item 1. Rubus, Punica, Filipendula, Myrica, Eugenia, Lagerstroemia, Momardana (Terminalia), Haematoxylon, Buckwheat A composition for inhibiting phosphodiesterase 5 activity, comprising a processed product of at least one plant selected from the group consisting of (Fallopia) and Uncaria.
Item 2. Item 2. The composition according to Item 1, wherein the plant belonging to the genus Rubus is at least one selected from the group consisting of Himalayan blackberry (Rubus armeniacus Focke), Aedesian strawberry (Rubus fruticosus), and American strawberry (Rubus strigosus). .
Item 3. Item 2. The composition according to Item 1, wherein the plant belonging to the genus Pomegranate is pomegranate (Punica granatum).
Item 4. Item 2. The composition according to Item 1, wherein the plant belonging to the genus Pleurotus is Filipendula ulmaria.
Item 5. Item 2. The composition according to Item 1, wherein the plant belonging to the genus Corpus is at least one selected from the group consisting of Myrica cerifera and Myrica rubura.
Item 6. Item 2. The composition according to Item 1, wherein the plant belonging to the genus Eugenia is at least one selected from the group consisting of Eugenia uniflora and clove (Eugenia aromaticum).
Item 7. Item 2. The composition according to Item 1, wherein the plant belonging to the genus Crape myrtle is banaba (Lagerstroemia speciosa).
Item 8. Item 2. The composition according to Item 1, wherein the plant belonging to the genus Momotamana is at least one selected from the group consisting of Terminalia catappa and Terminalia bellirica.
Item 9. Item 2. The composition according to Item 1, wherein the plant belonging to the genus Akaminoki is Haematoxylon campechianum.
Item 10. Item 2. The composition according to Item 1, wherein the plant belonging to the genus Buckwheat is a Japanese knotweed (Fallopia japonica).
Item 11. Item 2. The composition according to Item 1, wherein the plant belonging to the genus Kasakazura is Uncaria guianensis.
Item 12. Item 12. The composition according to any one of Items 1 to 11, which is for prevention or amelioration selected from the group consisting of penile erection function, lower urinary tract dysfunction, prostate hypertrophy and pulmonary hypertension.
Item 13. Item 13. The composition according to any one of Items 1 to 12, which is a food composition, a pharmaceutical composition, or a feed composition.
本発明によれば、ＰＤＥ５の活性を阻害できる。このため、本発明の組成物は、ｃＧＭＰの分解に伴う血流低下に起因する疾患、例えば陰茎勃起機能、下部尿路機能障害、前立腺肥大、肺高血圧症といった疾患の予防または改善を目的として使用することができる。
According to the present invention, the activity of PDE5 can be inhibited. Therefore, the composition of the present invention is used for the purpose of preventing or ameliorating diseases caused by decreased blood flow accompanying cGMP degradation such as penile erection function, lower urinary tract dysfunction, prostatic hypertrophy, and pulmonary hypertension. can do.
本発明は、キイチゴ属（Rubus）、ザクロ属（Punica）、シモツケソウ属（Filipendula）、ヤマモモ属（Myrica）、エウゲニア属（Eugenia）、サルスベリ属（Lagerstroemia）、モモタマナ属（Terminalia）、アカミノキ属（Haematoxylon）、ソバカズラ属（Fallopia）及びカギカズラ属（Uncaria）からなる群より選択される少なくとも１つの植物の加工物を含有する、ホスホジエステラーゼ５活性阻害用組成物を提供する。
The present invention relates to the genus Rubus, Punica, Filipendula, Myrica, Eugenia, Lagerstroemia, Terminalia, and Haematoxylon. ), A composition for inhibiting phosphodiesterase 5 activity, comprising a processed product of at least one plant selected from the group consisting of Fallopia and Uncaria.
本発明の組成物に有効成分として含まれる前記植物の加工物の原料として、それぞれ、キイチゴ属、ザクロ属、シモツケソウ属、ヤマモモ属、エウゲニア属、サルスベリ属、モモタマナ属、アカミノキ属、ソバカズラ属、カギカズラ属のいずれかに属する植物が挙げられる。
As raw materials for the processed plant products contained as an active ingredient in the composition of the present invention, the genus Raspberry, Pomegranate, Prunus spp., Prunus genus, Eugenia, Prunus spp., Prunus spp. Plants belonging to any of the genera can be mentioned.
キイチゴ属はバラ科に属し、本発明を制限するものではないが、該属に属する植物としてヒマラヤブラックベリー（Rubus armeniacus Focke）、セイヨウヤブイチゴ（Rubus fruticosus）、アメリカイチゴ（Rubus strigosus）等が例示される。
The genus Rubus belongs to the family Rosaceae and is not intended to limit the present invention. Examples of plants belonging to the genus include Himalayan blackberry (Rubus armeniacus Focke), Yabu strawberry (Rubus fruticosus), American strawberry (Rubus strigosus), etc. Is done.
ザクロ属はミソハギ科に属し、本発明を制限するものではないが、該属に属する植物としてザクロ（Punica granatum）等が例示される。
The pomegranate belongs to the family Lamiaceae and does not limit the present invention, but examples of plants belonging to the genus include pomegranate (Punica granatum).
シモツケソウ属はバラ科に属し、本発明を制限するものではないが、該属に属する植物としてセイヨウナツユキソウ（Filipendula ulmaria）等が例示される。
The genus Spiraea belongs to the family Rosaceae and does not limit the present invention, but examples of plants belonging to the genus include Filipendula ulmaria.
ヤマモモ属はヤマモモ科に属し、本発明を制限するものではないが、該属に属する植物としてシロコヤマモモ（Myrica cerifera）、ヤマモモ（Myrica rubura）等が例示される。
The genus genus belongs to the genus Dioscorea and does not limit the present invention, but examples of plants belonging to the genus include white licorice (Myrica cerifera), bayberry (Myrica rubura) and the like.
エウゲニア属はフトモモ科に属し、本発明を制限するものではないが、該属に属する植物としてタチバナアデク（Eugenia uniflora）、クローブ（Eugenia aromaticum）等が例示される。
The genus Eugenia belongs to the Myrtaceae family and does not limit the present invention, but examples of plants belonging to the genus include Eugenia uniflora and clove (Eugenia aromaticum).
サルスベリ属はミソハギ科に属し、本発明を制限するものではないが、該属に属する植物としてバナバ（Lagerstroemia speciosa）等が例示される。
Although the genus Crapery belongs to the family Lamiaceae and does not limit the present invention, examples of plants belonging to the genus include banaba (Lagerstroemia speciosa) and the like.
モモタマナ属はシクンシ科に属し、本発明を制限するものではないが、該属に属する植物としてモモタマナ（Terminalia catappa）、セイタカミロバラン（Terminalia bellirica）等が例示される。
Although the genus Momotamana belongs to the family Cypridaceae and does not limit the present invention, examples of plants belonging to the genus include Momotamana (Terminalia catappa), Seitamirobaran (Terminalia bellirica) and the like.
アカミノキ属はマメ科に属し、本発明を制限するものではないが、該属に属する植物としてアカミノキ（Haematoxylon campechianum）等が例示される。
The genus Akaminoki belongs to the leguminous family and does not limit the present invention, but examples of plants belonging to the genus include Akaminoki (Haematoxylon campechianum) and the like.
ソバカズラ属はタデ科に属し、本発明を制限するものではないが、該属に属する植物としてイタドリ（Fallopia japonica）等が例示される。
The buckwheat genus belongs to the family Taceae and does not limit the present invention, but examples of plants belonging to the genus include Fallopia japonica.
カギカズラ属はアカネ科に属し、本発明を制限するものではないが、該属に属する植物としてキャッツクロー（Uncaria guianensis）等が例示される。
The genus Kakazura belongs to the Rubiaceae family and does not limit the present invention, but examples of plants belonging to the genus include cats claw (Uncaria guianensis).
これらは１種単独で使用してもよく、２種以上を組み合わせて使用してもよい。
These may be used alone or in combination of two or more.
これらの植物であれば使用部位は特に限定されないが、葉、茎、果実、花、芽、枝、幹、樹皮、根、花蕾、種子、種皮等が例示され、各植物に応じて適宜選択すればよい。好ましくは葉、茎、果実、樹皮、根、幹、花蕾等が例示され、より好ましくは、キイチゴ属では葉、果実、ザクロ属では果実、シモツケソウ属では葉、茎、ヤマモモ属では樹皮、エウゲニア属では果実、花蕾、サルスベリ属では葉、モモタマナ属では果実、アカミノキ属では幹、ソバカズラ属では茎、葉、カギカズラ属では根、茎、葉が例示される。使用部位として、１種単独で使用してもよく、２種以上を組み合わせて使用してもよい。
The site of use is not particularly limited as long as these plants are used, but examples include leaves, stems, fruits, flowers, buds, branches, stems, bark, roots, florets, seeds, seed coats, and the like, which are appropriately selected according to each plant. That's fine. Preferably, leaves, stems, fruits, bark, roots, trunks, flower buds, etc. are exemplified, more preferably leaves in the genus Raspberry, fruits, fruits in the genus Pomegranate, leaves in the genus Prunus, stems, bark in the genus Genus, Eugenia In the genus, fruit, floret, crape myrtle leaves, momotamana genus fruit, red crested genus stem, buckwheat genus stem, leaf, and genus Kazura genus root, stem, leaf. As a part to be used, one kind may be used alone, or two or more kinds may be used in combination.
本発明において植物の加工物とは、前記原料となる植物の粉砕物、乾燥物、抽出物等が挙げられる。
In the present invention, the plant processed product includes a pulverized product, a dried product, and an extract of the plant as the raw material.
粉砕物は、ジェットミル等の本分野で公知の粉砕器により前記植物を粉砕したものであれば特に限定されない。
The pulverized product is not particularly limited as long as the plant is pulverized by a pulverizer known in the art such as a jet mill.
乾燥物は、前記植物を乾燥させたものであれば特に限定されず、天日乾燥、遠赤外線照射、乾燥機（熱風乾燥、冷風乾燥、真空凍結乾燥等）等の従来公知の乾燥方法に従って得ることができる。また、乾燥物中の水分量としては、１０重量％以下が好ましく、８重量％以下がより好ましい。本発明において乾燥物の形態は問わず、植物体そのものの乾燥物、乾燥物の粉砕物等のいずれでもよい。乾燥粉砕物は、前記粉砕物と同様の方法に従って乾燥物を粉砕することにより得ることができる。また、本発明においては乾燥物として、原料となる植物を発酵処理や酵素処理した後乾燥して得られたものを使用することもできる。
The dried product is not particularly limited as long as the plant is dried, and is obtained according to a conventionally known drying method such as sun drying, far-infrared irradiation, dryer (hot air drying, cold air drying, vacuum freeze drying, etc.) and the like. be able to. The water content in the dried product is preferably 10% by weight or less, and more preferably 8% by weight or less. In the present invention, the form of the dried product is not limited, and any of a dried product of the plant itself and a pulverized product of the dried product may be used. The dried pulverized product can be obtained by pulverizing the dried product according to the same method as the pulverized product. Moreover, in this invention, what was obtained by drying after making the plant used as a raw material a fermentation process or an enzyme process as a dried material can also be used.
抽出物の製造方法（抽出方法）及び抽出条件等は特に限定されず、従来公知の方法に従えばよい。例えば、前記植物をそのまま、必要に応じて裁断、粉砕または乾燥等したのち、搾取または溶媒抽出によって抽出物を得ることができる。溶媒抽出の方法としては、本分野において公知の方法を採用すればよく、例えば水（温水、熱水を含む）抽出、アルコール抽出、超臨界抽出等の従来公知の抽出方法を利用することができる。
製造 Extract production method (extraction method), extraction conditions and the like are not particularly limited, and may be a conventionally known method. For example, the plant can be cut, crushed or dried as necessary, and then extracted by extraction or solvent extraction. As a method for solvent extraction, a known method in this field may be employed. For example, a conventionally known extraction method such as water (including warm water and hot water) extraction, alcohol extraction, supercritical extraction, or the like can be used. .
溶媒抽出を行う場合、溶媒としては例えば水；メタノール、エタノール、イソプロパノール等の低級アルコールや、プロピレングリコール、１，３－ブチレングリコール等の多価アルコール等のアルコール類（無水、含水の別を問わない）；アセトン等のケトン類、ジエチルエーテル、ジオキサン、アセトニトリル、酢酸エチルエステル等のエステル類、キシレン、ベンゼン、クロロホルム等が挙げられる。溶媒として好ましくは水、低級アルコール、１，３－ブチレングリコール等であり、より好ましくは水、メタノール、エタノール、１，３－ブチレングリコールであり、更に好ましくは水、メタノール、含水エタノールである。これらの溶媒は１種単独で使用してもよく、２種以上を組み合わせて使用してもよい。
When performing solvent extraction, the solvent is, for example, water; alcohols such as lower alcohols such as methanol, ethanol and isopropanol, and polyhydric alcohols such as propylene glycol and 1,3-butylene glycol (anhydrous, regardless of water content). ); Ketones such as acetone, esters such as diethyl ether, dioxane, acetonitrile, and ethyl acetate, xylene, benzene, chloroform, and the like. The solvent is preferably water, lower alcohol, 1,3-butylene glycol or the like, more preferably water, methanol, ethanol or 1,3-butylene glycol, and still more preferably water, methanol or hydrous ethanol. These solvents may be used alone or in combination of two or more.
本発明において、このように溶媒抽出を経て得た抽出物を特に溶媒抽出物と称することができる。更に、本発明を制限するものではないが、前述のように例えば溶媒として水を用いた場合は水抽出物、低級アルコール類を用いた場合は低級アルコール抽出物、エタノールを用いた場合はエタノール抽出物等と称することができる。
In the present invention, the extract obtained through the solvent extraction in this way can be particularly referred to as a solvent extract. Furthermore, although the present invention is not limited, as described above, for example, when water is used as a solvent, a water extract, when a lower alcohol is used, a lower alcohol extract, when ethanol is used, an ethanol extraction is used. It can be called a thing etc.
得られた抽出物は、そのままの状態で使用してもよく、乾燥させて粉末状や顆粒状等の固形の状態で使用してもよい。また、必要に応じて、得られた抽出物に精製、濃縮処理、高活性画分の分離処理等を施してもよい。本発明を制限するものではないが、精製処理としては、濾過、イオン交換樹脂や活性炭カラム等を用いた吸着、脱色といった処理が挙げられる。また、濃縮処理としては、エバポレーター等の常法を利用できる。また、高活性画分の分離処理としては、ゲル濾過、吸着処理、シリカゲルカラムクロマトグラフィー、ＨＰＬＣ（High performance liquid chromatography）等の公知の分離処理を利用できる。
The obtained extract may be used as it is, or may be dried and used in a solid state such as powder or granule. In addition, the obtained extract may be subjected to purification, concentration treatment, separation treatment of highly active fraction, and the like as necessary. Although it does not restrict | limit this invention, processing, such as filtration, adsorption | suction using an ion exchange resin, an activated carbon column, etc., decoloring is mentioned as a refinement | purification process. As the concentration treatment, a conventional method such as an evaporator can be used. In addition, as the separation treatment of the high activity fraction, known separation treatments such as gel filtration, adsorption treatment, silica gel column chromatography, HPLC (High performance liquid chromatography) and the like can be used.
また、例えば、前述のようにして得られた抽出物（更にはその乾燥物、精製処理物、濃縮処理物、高活性画分）を、凍結乾燥処理に供して粉末化する方法、必要に応じてデキストリン、コーンスターチ、アラビアゴム等の賦形剤を添加して、スプレードライ処理により粉末化する方法等の従来公知の方法に従って粉末化し、本発明で用いる抽出物としてもよい。また、該抽出物を、必要に応じて水、エタノール等に溶解して用いてもよい。
In addition, for example, a method of subjecting the extract obtained as described above (and its dried product, purified product, concentrated product, and highly active fraction) to lyophilization and pulverization, if necessary Then, an extract such as dextrin, corn starch, gum arabic and the like may be added and powdered according to a conventionally known method such as a method of powdering by spray drying, and the extract used in the present invention may be used. Further, the extract may be used by dissolving it in water, ethanol or the like, if necessary.
前記植物の抽出物として好ましくは、原料となる植物（使用部位）を乾燥、破砕及び／または裁断し、好適な溶媒を使用して抽出、濾過して得られる抽出物、また、このようにして得られる抽出物を更に乾燥させることにより得られる抽出物が例示される。本発明を制限するものではなく、各植物または使用部位に応じて当業者が適宜抽出すればよいが、抽出物は、原料となる植物を１００ｇあたり、より好ましくは該植物の乾燥物、破砕物及び／または裁断物を１００ｇあたり、抽出溶媒１～５０リットルに浸漬させて、任意の温度（例えば１５～９０℃）で、必要に応じて攪拌しながら、任意の時間（例えば１０分～２４時間）抽出を行い、次いで濾過することにより得ることができる。本発明において植物の加工物として好ましくは植物抽出物（その乾燥物等を含む）である。
The plant extract is preferably an extract obtained by drying, crushing and / or cutting a plant (use site) as a raw material, and extracting and filtering using a suitable solvent. The extract obtained by further drying the obtained extract is illustrated. The present invention is not limited, and a person skilled in the art may appropriately extract according to each plant or use site. However, the extract is 100 g of a plant as a raw material, more preferably a dried product or a crushed product of the plant. And / or the cut material is immersed in 1 to 50 liters of extraction solvent per 100 g and at any temperature (for example, 15 to 90 ° C.) with stirring as necessary for any time (for example, 10 minutes to 24 hours). ) Extraction, followed by filtration. In the present invention, a plant extract (including a dried product thereof) is preferably used as a processed plant product.
本発明において使用する植物の加工物は市販品でもよく、市販品に対して更に乾燥等の処理を適宜施したものでもよい。
The processed plant product used in the present invention may be a commercially available product, or may be a product obtained by appropriately subjecting the commercially available product to a treatment such as drying.
このようにして得た植物の加工物は、１種単独で使用してもよく、２種以上を組み合わせて使用してもよい。
The plant processed product thus obtained may be used alone or in combination of two or more.
本発明の組成物中の前記植物の加工物の含有量は、組成物中に前記植物の加工物が含まれていればよく、本発明の効果が得られる限り制限されない。組成物中、前記植物の加工物が、乾燥物換算で、０重量％より多く含まれていることが例示され、好ましくは０重量％より多く１００重量％未満であることが例示され、より好ましくは０．００１～９９重量％が例示される。２種以上の加工物を用いる場合、その総量が該値を充足する。加工物の乾燥物は、加工物を凍結乾燥処理することにより得られる。凍結乾燥処理は、一般的なエバポレーターを用いた減圧濃縮及び真空状態での凍結乾燥により行う。より詳細な処理手順は後述する実施例に従う。
The content of the processed plant product in the composition of the present invention is not limited as long as the processed plant product is contained in the composition, and the effect of the present invention is obtained. In the composition, it is exemplified that the processed product of the plant is contained in an amount of more than 0% by weight, preferably more than 0% by weight and less than 100% by weight, more preferably in terms of dry matter. Is exemplified by 0.001 to 99% by weight. When two or more kinds of workpieces are used, the total amount satisfies the value. A dried product is obtained by freeze-drying the processed product. The freeze-drying process is performed by vacuum concentration using a general evaporator and freeze-drying in a vacuum state. A more detailed processing procedure follows an embodiment described later.
また、本発明の組成物において、前記植物の加工物の投与（摂取）量は、本発明の効果が奏される限り特に限定されず、対象者（対象動物）の体格、年齢、症状、適用形態、使用目的、期待される効果の程度等に応じて適宜設定すればよい。本発明を制限するものではないが、１日投与（摂取）量として、体重６０ｋｇの成人を基準として、前記植物の加工物は総量で（乾燥重量換算として）、好ましくは０．００１～８０００ｍｇ、より好ましくは０．０１～５０００ｍｇが例示される。本発明の組成物は、１日あたり単回投与（摂取）であってもよく複数回投与（摂取）であってもよい。
Further, in the composition of the present invention, the administration (intake) amount of the processed plant product is not particularly limited as long as the effect of the present invention is exhibited, and the physique, age, symptom, application of the subject (target animal) What is necessary is just to set suitably according to a form, the intended purpose, the grade of the effect expected, etc. Although not limiting the present invention, as a daily administration (intake) amount, the processed product of the plant is a total amount (in terms of dry weight), preferably 0.001 to 8000 mg, based on an adult with a body weight of 60 kg. More preferably, 0.01 to 5000 mg is exemplified. The composition of the present invention may be single dose (intake) or multiple dose (intake) per day.
本発明の組成物は、経口、非経口の別を問わない。本発明の組成物の形態も制限されず、目的に応じて適宜設定すればよい。本発明の組成物の形態として、液剤、乳剤、懸濁剤、シロップ剤、エキス剤、酒精剤、エリキシル剤等の液状形態、散剤、顆粒剤、細粒剤、錠剤、丸剤、カプセル剤（ハードカプセル、ソフトカプセルを含む）、トローチ、チュアブル、ゲル状、クリーム状、ペースト状、ムース状、シート状、液状形態の凍結乾燥物等の半固形または固形形態、この他、エアゾール剤等、貼付剤、ハップ剤、経皮吸収型製剤等の各種形態が例示される。
The composition of the present invention may be oral or parenteral. The form of the composition of the present invention is not limited, and may be appropriately set depending on the purpose. As the form of the composition of the present invention, liquid forms such as liquids, emulsions, suspensions, syrups, extracts, spirits, elixirs, powders, granules, fine granules, tablets, pills, capsules ( (Including hard capsules and soft capsules), troches, chewables, gels, creams, pastes, mousses, sheets, semi-solid or solid forms such as lyophilizates in liquid form, in addition, aerosols and other patches, Various forms such as a haptic agent and a transdermal absorption preparation are exemplified.
また、例えば本発明の組成物が固形形態である場合、これは水等と混合して使用してもよく、また、本発明の組成物は徐放性の剤形であってもよい。また、例えば錠剤は、必要に応じて、従来公知の剤皮を施した錠剤、例えば糖衣錠、ゼラチン被包錠、腸溶被錠、フィルムコーティング錠、あるいは二重錠、多層錠とすることができる。
Also, for example, when the composition of the present invention is in a solid form, it may be used by mixing with water or the like, and the composition of the present invention may be in a sustained-release dosage form. In addition, for example, the tablet can be a tablet with a conventionally known coating, such as a sugar-coated tablet, a gelatin-encapsulated tablet, an enteric-coated tablet, a film-coated tablet, a double tablet, or a multilayer tablet, if necessary. .
また、本発明の組成物の使用態様も制限されず、目的に応じて適宜設定すればよい。本発明の組成物の使用態様として、食品組成物（飲料を含む、保健機能食品（特定保健用食品、栄養機能食品、機能性表示食品、サプリメント等を含む）、病者用食品を含む）、医薬組成物、飼料組成物、また、食品組成物、医薬組成物、飼料等への添加剤等として使用することができる。
Further, the use mode of the composition of the present invention is not limited, and may be appropriately set according to the purpose. Examples of usage of the composition of the present invention include food compositions (including beverages, health functional foods (including foods for specified health use, nutritional functional foods, functional display foods, supplements, etc.), foods for the sick, It can be used as an additive to pharmaceutical compositions, feed compositions, food compositions, pharmaceutical compositions, feeds, and the like.
本発明の組成物は、前述の各種形態、使用態様等における従来公知の通常の手順に従い製造すればよく、必要に応じて、薬学的に許容される成分、香粧品科学的に許容される成分、可食性の成分といった任意の成分と混合等して製造すればよい。該任意の成分として、溶剤（水、メタノール、エタノール、イソプロパノール等の低級アルコール、プロピレングリコール、１，３－ブチレングリコール等の多価アルコール等のアルコール類（無水、含水の別を問わない）等）、賦形剤、崩壊剤、希釈剤、滑沢剤、香料、着色料、甘味料、矯味剤、懸濁剤、湿潤剤、乳化剤、可溶化剤、分散剤、緩衝剤、結合剤、浸透促進剤、安定剤、増量剤、防腐剤、増粘剤、ｐＨ調整剤、界面活性剤、コーティング剤、吸収促進剤、吸着剤、充填剤、酸化防止剤、抗炎症剤、清涼剤、皮膜形成剤、ゲル化剤、アミノ酸、ビタミン、酵素、各種栄養成分等が例示される。これらは１種単独で使用してもよく、２種以上を組み合わせて使用してもよい。
The composition of the present invention may be produced according to conventionally known ordinary procedures in the above-mentioned various forms, usage modes, etc., and if necessary, pharmaceutically acceptable ingredients, cosmetically acceptable ingredients. What is necessary is just to mix and manufacture with arbitrary components, such as an edible component. Solvents (water, lower alcohols such as methanol, ethanol and isopropanol, alcohols such as polyhydric alcohols such as propylene glycol and 1,3-butylene glycol (anhydrous, regardless of water content), etc.) , Excipients, disintegrants, diluents, lubricants, flavors, colorants, sweeteners, flavoring agents, suspending agents, wetting agents, emulsifiers, solubilizers, dispersants, buffers, binders, penetration enhancers Agent, stabilizer, extender, preservative, thickener, pH adjuster, surfactant, coating agent, absorption enhancer, adsorbent, filler, antioxidant, anti-inflammatory agent, cooling agent, film-forming agent And gelling agents, amino acids, vitamins, enzymes, various nutritional components, and the like. These may be used alone or in combination of two or more.
本発明において、組成物の対象者（対象動物）も制限されないが、ヒト、ヒト以外の哺乳動物が例示される。ヒト以外の哺乳動物としては、ホスホジエステラーゼ５がｃＧＭＰの分解促進を図っている動物が挙げられ、マウス、ラット、モルモット、ウサギ、イヌ、ネコ、サル、ブタ、牛、馬等の動物、好ましくはマウス、ラット、モルモット、ウサギ、イヌ、サル等の動物が例示される。
In the present invention, the subject (target animal) of the composition is not limited, but humans and mammals other than humans are exemplified. Examples of mammals other than humans include animals in which phosphodiesterase 5 promotes the degradation of cGMP, and animals such as mice, rats, guinea pigs, rabbits, dogs, cats, monkeys, pigs, cows, horses, preferably mice. And animals such as rats, guinea pigs, rabbits, dogs and monkeys.
本発明の組成物によれば、前記植物の加工物を有効成分としてホスホジエステラーゼ５（ＰＤＥ５）の活性を阻害することができる。このことから、本発明は、前記植物の加工物を用いることを特徴とするＰＤＥ５活性阻害用組成物の製造方法を提供するといえる。また、本発明は、前記植物の加工物を調製する工程を含有する、ＰＤＥ５活性阻害用組成物の製造方法を提供するといえる。また、本発明は、前記植物の加工物を用いることを特徴とする、ＰＤＥ５活性阻害方法を提供するといえる。
According to the composition of the present invention, the activity of phosphodiesterase 5 (PDE5) can be inhibited using the processed plant product as an active ingredient. From this, it can be said that this invention provides the manufacturing method of the composition for PDE5 activity inhibition characterized by using the processed material of the said plant. Moreover, it can be said that this invention provides the manufacturing method of the composition for PDE5 activity inhibition containing the process of preparing the processed material of the said plant. Moreover, it can be said that this invention provides the PDE5 activity inhibition method characterized by using the processed material of the said plant.
このように本発明の組成物によれば、ＰＤＥ５の活性を阻害できる。このことから、本発明によればｃＧＭＰの分解を抑制することができ、ＰＤＥ５の活性や局所血流低下に起因する疾患の予防または改善を目的として本発明の組成物を使用することができる。
Thus, according to the composition of the present invention, the activity of PDE5 can be inhibited. Therefore, according to the present invention, the degradation of cGMP can be suppressed, and the composition of the present invention can be used for the purpose of preventing or ameliorating diseases caused by PDE5 activity and local blood flow reduction.
このため、本発明の組成物は、本発明を制限するものではないが、陰茎勃起機能、下部尿路機能障害、前立腺肥大、肺高血圧症等の予防または改善に有用である。例えば、ＰＤＥ５阻害作用により平滑筋が弛緩し、これにより陰茎海綿体への血流を増加させることで陰茎勃起機能の改善を図ることができ、泌尿器系への血流を増加させることで下部尿路障害の改善を図ることができ、前立腺や尿道の血流を増加させることで前立腺肥大の緩和を図ることができ、肺組織への血流を増加させることで肺動脈圧の低下を図ることができる。
Therefore, the composition of the present invention is useful for the prevention or improvement of penile erection function, lower urinary tract dysfunction, prostatic hypertrophy, pulmonary hypertension, etc., although the present invention is not limited thereto. For example, smooth muscle is relaxed by the PDE5 inhibitory action, thereby improving the penile erection function by increasing the blood flow to the cavernous corpus cavernosum, and lowering the lower urine by increasing the blood flow to the urinary system Can improve tract obstruction, can increase prostate blood flow in the prostate and urethra, can alleviate prostate enlargement, and can increase blood flow to the lung tissue to reduce pulmonary artery pressure it can.
このことから、本発明の組成物はまた、男性機能が気になる対象者、排尿機能が気になる対象者等に好ましく適用することができる。
Therefore, the composition of the present invention can also be preferably applied to subjects who are concerned about male function, subjects who are concerned about urination function, and the like.
また、本発明の組成物は、ＰＤＥ５活性阻害薬、陰茎勃起機能（不全）治療薬、下部尿路機能障害治療薬、前立腺肥大治療薬、肺高血圧症治療薬（特に肺動脈性肺高血圧症）等としても使用できる
The composition of the present invention includes PDE5 activity inhibitor, penile erection function (deficiency) treatment, lower urinary tract dysfunction treatment, prostate hypertrophy treatment, pulmonary hypertension treatment (particularly pulmonary arterial pulmonary hypertension), etc. Can also be used as
以下、実施例を示して本発明をより詳細に説明するが、本発明はこれらに限定されない。
Hereinafter, the present invention will be described in more detail with reference to examples, but the present invention is not limited thereto.
試験例１
１．植物の加工物
表１に示す植物を原料として、各植物の抽出物を準備した。具体的には、実施例１、５、９及び１０については次の手順に従い抽出物を調製し、その他の実施例については市販品を用いた。 Test example 1
1. Processed Plants Extracts of each plant were prepared using the plants shown in Table 1 as raw materials. Specifically, for Examples 1, 5, 9 and 10, extracts were prepared according to the following procedure, and commercially available products were used for the other examples.
１．植物の加工物
表１に示す植物を原料として、各植物の抽出物を準備した。具体的には、実施例１、５、９及び１０については次の手順に従い抽出物を調製し、その他の実施例については市販品を用いた。 Test example 1
1. Processed Plants Extracts of each plant were prepared using the plants shown in Table 1 as raw materials. Specifically, for Examples 1, 5, 9 and 10, extracts were prepared according to the following procedure, and commercially available products were used for the other examples.
実施例１：ヒマラヤブラックベリー
ヒマラヤブラックベリーの葉の乾燥物50ｇを破砕し、水を1000 ml添加して80℃、1時間で抽出処理を実施した。得られた抽出物をミラクロス（メルク・ミリポア社製）にて濾過し、不溶性成分を除去した濾液を凍結乾燥することで、ヒマラヤブラックベリー抽出物（抽出乾燥物7.9 g）を得た。 Example 1: Himalayan Blackberry Himalayan Blackberry leaves 50 g were crushed, 1000 ml of water was added, and extraction treatment was performed at 80 ° C. for 1 hour. The obtained extract was filtered through Miracloth (manufactured by Merck Millipore), and the filtrate from which insoluble components had been removed was freeze-dried to obtain a Himalayan blackberry extract (7.9 g of dried extract).
ヒマラヤブラックベリーの葉の乾燥物50ｇを破砕し、水を1000 ml添加して80℃、1時間で抽出処理を実施した。得られた抽出物をミラクロス（メルク・ミリポア社製）にて濾過し、不溶性成分を除去した濾液を凍結乾燥することで、ヒマラヤブラックベリー抽出物（抽出乾燥物7.9 g）を得た。 Example 1: Himalayan Blackberry Himalayan Blackberry leaves 50 g were crushed, 1000 ml of water was added, and extraction treatment was performed at 80 ° C. for 1 hour. The obtained extract was filtered through Miracloth (manufactured by Merck Millipore), and the filtrate from which insoluble components had been removed was freeze-dried to obtain a Himalayan blackberry extract (7.9 g of dried extract).
実施例２：セイヨウヤブイチゴ
セイヨウヤブイチゴの葉の抽出物（日本新薬社製特注、粉末乾燥物）を用いた。本抽出物は、セイヨウヤブイチゴの葉の乾燥物を破砕し、メタノールを添加して抽出し、得られた抽出物を濾過し、不溶性成分を除去した濾液を凍結乾燥することにより得たものである。 Example 2: Yab Strawberry An extract of Yab Strawberry (special order made by Nippon Shinyaku Co., Ltd., dry powder) was used. This extract was obtained by crushing dried yab strawberry leaves, extracting with methanol, filtering the resulting extract, and lyophilizing the filtrate from which insoluble components had been removed. is there.
セイヨウヤブイチゴの葉の抽出物（日本新薬社製特注、粉末乾燥物）を用いた。本抽出物は、セイヨウヤブイチゴの葉の乾燥物を破砕し、メタノールを添加して抽出し、得られた抽出物を濾過し、不溶性成分を除去した濾液を凍結乾燥することにより得たものである。 Example 2: Yab Strawberry An extract of Yab Strawberry (special order made by Nippon Shinyaku Co., Ltd., dry powder) was used. This extract was obtained by crushing dried yab strawberry leaves, extracting with methanol, filtering the resulting extract, and lyophilizing the filtrate from which insoluble components had been removed. is there.
実施例３：アメリカイチゴ
アメリカイチゴの葉及び果実の抽出物（日本新薬社製特注、粉末乾燥物）を用いた。本抽出物は、アメリカイチゴの葉及び果実の乾燥物を破砕し、メタノールを添加して抽出し、得られた抽出物を濾過し、不溶性成分を除去した濾液を凍結乾燥することにより得たものである。 Example 3: American Strawberry American strawberry leaf and fruit extracts (made by Nippon Shinyaku Co., Ltd., dry powder) were used. This extract was obtained by crushing a dried product of American strawberry leaves and fruits, extracting by adding methanol, filtering the resulting extract, and lyophilizing the filtrate from which insoluble components had been removed. It is.
アメリカイチゴの葉及び果実の抽出物（日本新薬社製特注、粉末乾燥物）を用いた。本抽出物は、アメリカイチゴの葉及び果実の乾燥物を破砕し、メタノールを添加して抽出し、得られた抽出物を濾過し、不溶性成分を除去した濾液を凍結乾燥することにより得たものである。 Example 3: American Strawberry American strawberry leaf and fruit extracts (made by Nippon Shinyaku Co., Ltd., dry powder) were used. This extract was obtained by crushing a dried product of American strawberry leaves and fruits, extracting by adding methanol, filtering the resulting extract, and lyophilizing the filtrate from which insoluble components had been removed. It is.
実施例４：ザクロ
ザクロの果皮の抽出物（商品名ザクロ果皮エキス末、香栄興業製、粉末乾燥物）を用いた。 Example 4: pericarp extract of pomegranate pomegranate (trade name pomegranate rind extract powder, Koei Kogyo Co., Ltd., powder dry matter) was used.
ザクロの果皮の抽出物（商品名ザクロ果皮エキス末、香栄興業製、粉末乾燥物）を用いた。 Example 4: pericarp extract of pomegranate pomegranate (trade name pomegranate rind extract powder, Koei Kogyo Co., Ltd., powder dry matter) was used.
実施例５：セイヨウナツユキソウ
セイヨウナツユキソウの茎及び葉の乾燥物40ｇを破砕し、水を1000ml添加して80℃、1時間で抽出処理を実施した。得られた抽出物をミラクロス（メルク・ミリポア社製）にて濾過し、不溶性成分を除去した濾液を凍結乾燥することで、セイヨウナツユキソウ抽出物（抽出乾燥物9.9 g）を得た。 Example 5: 40 g of dried stems and leaves of C. communis was crushed, 1000 ml of water was added, and extraction was performed at 80 ° C. for 1 hour. The obtained extract was filtered with Miracloth (manufactured by Merck Millipore), and the filtrate from which insoluble components had been removed was freeze-dried to obtain a licorice extract (9.9 g of dried extract).
セイヨウナツユキソウの茎及び葉の乾燥物40ｇを破砕し、水を1000ml添加して80℃、1時間で抽出処理を実施した。得られた抽出物をミラクロス（メルク・ミリポア社製）にて濾過し、不溶性成分を除去した濾液を凍結乾燥することで、セイヨウナツユキソウ抽出物（抽出乾燥物9.9 g）を得た。 Example 5: 40 g of dried stems and leaves of C. communis was crushed, 1000 ml of water was added, and extraction was performed at 80 ° C. for 1 hour. The obtained extract was filtered with Miracloth (manufactured by Merck Millipore), and the filtrate from which insoluble components had been removed was freeze-dried to obtain a licorice extract (9.9 g of dried extract).
実施例６：シロコヤマモモ
シロコヤマモモの樹皮の抽出物（日本新薬社製特注、粉末乾燥物）を用いた。本抽出物は、シロコヤマモモの樹皮の乾燥物を破砕し、メタノールを添加して抽出し、得られた抽出物を濾過し、不溶性成分を除去した濾液を凍結乾燥することにより得たものである。 Example 6: An extract of bark of white bayberry (special order made by Nippon Shinyaku Co., Ltd., dry powder) was used. This extract was obtained by crushing a dried white bark bark, adding methanol for extraction, filtering the resulting extract, and lyophilizing the filtrate from which insoluble components had been removed. .
シロコヤマモモの樹皮の抽出物（日本新薬社製特注、粉末乾燥物）を用いた。本抽出物は、シロコヤマモモの樹皮の乾燥物を破砕し、メタノールを添加して抽出し、得られた抽出物を濾過し、不溶性成分を除去した濾液を凍結乾燥することにより得たものである。 Example 6: An extract of bark of white bayberry (special order made by Nippon Shinyaku Co., Ltd., dry powder) was used. This extract was obtained by crushing a dried white bark bark, adding methanol for extraction, filtering the resulting extract, and lyophilizing the filtrate from which insoluble components had been removed. .
実施例７：ヤマモモ
ヤマモモの樹皮の抽出物（日本新薬社製特注、粉末乾燥物）を用いた。本抽出物は、ヤマモモの樹皮の乾燥物を破砕し、メタノールを添加して抽出し、得られた抽出物を濾過し、不溶性成分を除去した濾液を凍結乾燥することにより得たものである。 Example 7: An extract of bark of yamamomo yamamomo (special order made by Nippon Shinyaku Co., Ltd., dry powder) was used. This extract was obtained by crushing a dried product of bayberry bark, extracting by adding methanol, filtering the obtained extract, and lyophilizing the filtrate from which insoluble components were removed.
ヤマモモの樹皮の抽出物（日本新薬社製特注、粉末乾燥物）を用いた。本抽出物は、ヤマモモの樹皮の乾燥物を破砕し、メタノールを添加して抽出し、得られた抽出物を濾過し、不溶性成分を除去した濾液を凍結乾燥することにより得たものである。 Example 7: An extract of bark of yamamomo yamamomo (special order made by Nippon Shinyaku Co., Ltd., dry powder) was used. This extract was obtained by crushing a dried product of bayberry bark, extracting by adding methanol, filtering the obtained extract, and lyophilizing the filtrate from which insoluble components were removed.
実施例８：タチバナアデク
タチバナアデクの果実の抽出物（日本新薬社製特注、粉末乾燥物）を用いた。本抽出物は、タチバナアデクの果実の乾燥物を破砕し、メタノールを添加して抽出し、得られた抽出物を濾過し、不溶性成分を除去した濾液を凍結乾燥することにより得たものである。 Example 8: Tachibana adecta fruit extract (special order made by Nippon Shinyaku Co., Ltd., dry powder) was used. This extract was obtained by crushing the dried fruit of Tachibana adek, adding methanol for extraction, filtering the resulting extract, and freeze-drying the filtrate from which insoluble components had been removed. .
タチバナアデクの果実の抽出物（日本新薬社製特注、粉末乾燥物）を用いた。本抽出物は、タチバナアデクの果実の乾燥物を破砕し、メタノールを添加して抽出し、得られた抽出物を濾過し、不溶性成分を除去した濾液を凍結乾燥することにより得たものである。 Example 8: Tachibana adecta fruit extract (special order made by Nippon Shinyaku Co., Ltd., dry powder) was used. This extract was obtained by crushing the dried fruit of Tachibana adek, adding methanol for extraction, filtering the resulting extract, and freeze-drying the filtrate from which insoluble components had been removed. .
実施例９：クローブ
クローブの花蕾の乾燥物50ｇを破砕し、水を1000ml添加して80℃、 1時間で抽出処理を実施した。得られた抽出物をミラクロス（メルク・ミリポア社製）にて濾過し、不溶性成分を除去した濾液を凍結乾燥することで、クローブ抽出物（抽出乾燥物10.1 g）を得た。 Example 9: 50 g of dried clove clove flower was crushed, 1000 ml of water was added, and extraction treatment was performed at 80 ° C. for 1 hour. The obtained extract was filtered with Miracloth (manufactured by Merck Millipore), and the filtrate from which insoluble components were removed was freeze-dried to obtain a clove extract (10.1 g of dried extract).
クローブの花蕾の乾燥物50ｇを破砕し、水を1000ml添加して80℃、 1時間で抽出処理を実施した。得られた抽出物をミラクロス（メルク・ミリポア社製）にて濾過し、不溶性成分を除去した濾液を凍結乾燥することで、クローブ抽出物（抽出乾燥物10.1 g）を得た。 Example 9: 50 g of dried clove clove flower was crushed, 1000 ml of water was added, and extraction treatment was performed at 80 ° C. for 1 hour. The obtained extract was filtered with Miracloth (manufactured by Merck Millipore), and the filtrate from which insoluble components were removed was freeze-dried to obtain a clove extract (10.1 g of dried extract).
実施例１０：バナバ
バナバ葉の乾燥物60ｇを破砕し、50質量％エタノール（水とエタノールとの質量比１：１）を900ml添加して25℃、12時間で抽出処理を実施した。得られた抽出物をミラクロス（メルク・ミリポア社製）にて濾過し、不溶性成分を除去した濾液からエタノールを留去した後、凍結乾燥することで、バナバ抽出物（抽出乾燥物8.9 g）を得た。 Example 10: banaba banaba crushed dry matter 60g leaf (mass ratio of water and ethanol 1: 1) 50 wt% ethanol 900ml added to 25 ° C., was carried out extraction at 12 hours. The obtained extract was filtered through Miracloth (Merck Millipore), ethanol was distilled off from the filtrate from which insoluble components had been removed, and then freeze-dried to obtain a banaba extract (8.9 g dry extract). Obtained.
バナバ葉の乾燥物60ｇを破砕し、50質量％エタノール（水とエタノールとの質量比１：１）を900ml添加して25℃、12時間で抽出処理を実施した。得られた抽出物をミラクロス（メルク・ミリポア社製）にて濾過し、不溶性成分を除去した濾液からエタノールを留去した後、凍結乾燥することで、バナバ抽出物（抽出乾燥物8.9 g）を得た。 Example 10: banaba banaba crushed dry matter 60g leaf (mass ratio of water and ethanol 1: 1) 50 wt% ethanol 900ml added to 25 ° C., was carried out extraction at 12 hours. The obtained extract was filtered through Miracloth (Merck Millipore), ethanol was distilled off from the filtrate from which insoluble components had been removed, and then freeze-dried to obtain a banaba extract (8.9 g dry extract). Obtained.
実施例１１：モモタマナ
モモタマナの果実の抽出物（日本新薬社製特注、粉末乾燥物）を用いた。本抽出物は、モモタマナの果実の乾燥物を破砕し、メタノールを添加して抽出し、得られた抽出物を濾過し、不溶性成分を除去した濾液を凍結乾燥することにより得たものである。 Example 11: An extract of the fruit of Momota Mana Momota Mana (special order made by Nippon Shinyaku Co., Ltd., dry powder) was used. This extract was obtained by crushing a dried product of Momotamana fruit, adding methanol to perform extraction, filtering the obtained extract, and freeze-drying the filtrate from which insoluble components were removed.
モモタマナの果実の抽出物（日本新薬社製特注、粉末乾燥物）を用いた。本抽出物は、モモタマナの果実の乾燥物を破砕し、メタノールを添加して抽出し、得られた抽出物を濾過し、不溶性成分を除去した濾液を凍結乾燥することにより得たものである。 Example 11: An extract of the fruit of Momota Mana Momota Mana (special order made by Nippon Shinyaku Co., Ltd., dry powder) was used. This extract was obtained by crushing a dried product of Momotamana fruit, adding methanol to perform extraction, filtering the obtained extract, and freeze-drying the filtrate from which insoluble components were removed.
実施例１２：セイタカミロバラン
セイタカミロバランの果実の抽出物（日本新薬社製特注、粉末乾燥物）を用いた。本抽出物は、セイタカミロバランの果実の乾燥物を破砕し、メタノールを添加して抽出し、得られた抽出物を濾過し、不溶性成分を除去した濾液を凍結乾燥することにより得たものである。 Example 12: Seitakamirobaran Fruit extract of Seitakamirobalan (special order made by Nippon Shinyaku Co., Ltd., dry powder) was used. This extract was obtained by crushing the dried fruit of Seitacamilobaran, adding methanol to extract it, filtering the resulting extract, and freeze-drying the filtrate from which insoluble components had been removed. is there.
セイタカミロバランの果実の抽出物（日本新薬社製特注、粉末乾燥物）を用いた。本抽出物は、セイタカミロバランの果実の乾燥物を破砕し、メタノールを添加して抽出し、得られた抽出物を濾過し、不溶性成分を除去した濾液を凍結乾燥することにより得たものである。 Example 12: Seitakamirobaran Fruit extract of Seitakamirobalan (special order made by Nippon Shinyaku Co., Ltd., dry powder) was used. This extract was obtained by crushing the dried fruit of Seitacamilobaran, adding methanol to extract it, filtering the resulting extract, and freeze-drying the filtrate from which insoluble components had been removed. is there.
実施例１３：アカミノキ
アカミノキの幹の抽出物（日本新薬社製特注、粉末乾燥物）を用いた。本抽出物は、アカミノキの幹の乾燥物を破砕し、メタノールを添加して抽出し、得られた抽出物を濾過し、不溶性成分を除去した濾液を凍結乾燥することにより得たものである。 Example 13: haematoxylum campechianum stem extract of haematoxylum campechianum (Nippon Shinyaku Co. custom, powder dry matter) was used. This extract was obtained by crushing a dried stem of Akaminoki trunk, adding methanol for extraction, filtering the resulting extract, and freeze-drying the filtrate from which insoluble components had been removed.
アカミノキの幹の抽出物（日本新薬社製特注、粉末乾燥物）を用いた。本抽出物は、アカミノキの幹の乾燥物を破砕し、メタノールを添加して抽出し、得られた抽出物を濾過し、不溶性成分を除去した濾液を凍結乾燥することにより得たものである。 Example 13: haematoxylum campechianum stem extract of haematoxylum campechianum (Nippon Shinyaku Co. custom, powder dry matter) was used. This extract was obtained by crushing a dried stem of Akaminoki trunk, adding methanol for extraction, filtering the resulting extract, and freeze-drying the filtrate from which insoluble components had been removed.
実施例１４：イタドリ
イタドリの茎及び葉の抽出物（日本新薬社製特注、粉末乾燥物）を用いた。本抽出物は、イタドリの茎及び葉の乾燥物を破砕し、メタノールを添加して抽出し、得られた抽出物を濾過し、不溶性成分を除去した濾液を凍結乾燥することにより得たものである。 Example 14: Extracts of stems and leaves of Japanese knotweed weeds (special order made by Nippon Shinyaku Co., Ltd., dry powder) were used. This extract was obtained by crushing dried weedbird stems and leaves, extracting with methanol, filtering the resulting extract, and freeze-drying the filtrate from which insoluble components had been removed. is there.
イタドリの茎及び葉の抽出物（日本新薬社製特注、粉末乾燥物）を用いた。本抽出物は、イタドリの茎及び葉の乾燥物を破砕し、メタノールを添加して抽出し、得られた抽出物を濾過し、不溶性成分を除去した濾液を凍結乾燥することにより得たものである。 Example 14: Extracts of stems and leaves of Japanese knotweed weeds (special order made by Nippon Shinyaku Co., Ltd., dry powder) were used. This extract was obtained by crushing dried weedbird stems and leaves, extracting with methanol, filtering the resulting extract, and freeze-drying the filtrate from which insoluble components had been removed. is there.
実施例１５：キャッツクロー
キャッツクローの根、茎及び葉の抽出物（日本新薬社製特注、粉末乾燥物）を用いた。本抽出物は、キャッツクローの根、茎及び葉の乾燥物を破砕し、メタノールを添加して抽出し、得られた抽出物を濾過し、不溶性成分を除去した濾液を凍結乾燥することにより得たものである。 Example 15: Cats Claw Cats Claw root, stem and leaf extracts (made by Nippon Shinyaku Co., Ltd., dry powder) were used. This extract was obtained by crushing dried catscrow roots, stems and leaves, adding methanol to extract, filtering the resulting extract, and freeze-drying the filtrate from which insoluble components had been removed. It is a thing.
キャッツクローの根、茎及び葉の抽出物（日本新薬社製特注、粉末乾燥物）を用いた。本抽出物は、キャッツクローの根、茎及び葉の乾燥物を破砕し、メタノールを添加して抽出し、得られた抽出物を濾過し、不溶性成分を除去した濾液を凍結乾燥することにより得たものである。 Example 15: Cats Claw Cats Claw root, stem and leaf extracts (made by Nippon Shinyaku Co., Ltd., dry powder) were used. This extract was obtained by crushing dried catscrow roots, stems and leaves, adding methanol to extract, filtering the resulting extract, and freeze-drying the filtrate from which insoluble components had been removed. It is a thing.
比較例：クロショウガ
クロショウガの根茎の抽出物（商品名黒ショウガエキス－Ｐ、オリザ油化製、粉末乾燥物）を用いた。クロショウガは、従来、ホスホジエステラーゼ(PDE)に対して阻害作用を有していると知られている植物である。 Comparative Example: An extract of rhizomes of black ginger black ginger (trade name: black ginger extract-P, manufactured by Oriza Oil Co., Ltd., dried powder) was used. Black ginger is a plant that is conventionally known to have an inhibitory action on phosphodiesterase (PDE).
クロショウガの根茎の抽出物（商品名黒ショウガエキス－Ｐ、オリザ油化製、粉末乾燥物）を用いた。クロショウガは、従来、ホスホジエステラーゼ(PDE)に対して阻害作用を有していると知られている植物である。 Comparative Example: An extract of rhizomes of black ginger black ginger (trade name: black ginger extract-P, manufactured by Oriza Oil Co., Ltd., dried powder) was used. Black ginger is a plant that is conventionally known to have an inhibitory action on phosphodiesterase (PDE).
２．ホスホジエステラーゼ(PDE)5阻害活性の測定
前記１．で準備した各抽出物の、PDE5に対する阻害活性を測定した（n=3）。本測定において、PDE5A Assay Kit (♯60350)（BPSバイオサイエンス社製）、96wellプレート、ピペットマン、PerkinElmer EnVision 2102 Multilabel Reader（パーキンエルマー社製）を用い、キットに付帯の手順書に従い、阻害活性を測定した。 2. Measurement of phosphodiesterase (PDE) 5 inhibitory activity The inhibitory activity against PDE5 of each of the extracts prepared in (n = 3) was measured. In this measurement, PDE5A Assay Kit (# 60350) (manufactured by BPS Bioscience), 96-well plate, Pipetman, PerkinElmer EnVision 2102 Multilabel Reader (manufactured by PerkinElmer) was used to measure the inhibitory activity according to the instructions attached to the kit. did.
前記１．で準備した各抽出物の、PDE5に対する阻害活性を測定した（n=3）。本測定において、PDE5A Assay Kit (♯60350)（BPSバイオサイエンス社製）、96wellプレート、ピペットマン、PerkinElmer EnVision 2102 Multilabel Reader（パーキンエルマー社製）を用い、キットに付帯の手順書に従い、阻害活性を測定した。 2. Measurement of phosphodiesterase (PDE) 5 inhibitory activity The inhibitory activity against PDE5 of each of the extracts prepared in (n = 3) was measured. In this measurement, PDE5A Assay Kit (# 60350) (manufactured by BPS Bioscience), 96-well plate, Pipetman, PerkinElmer EnVision 2102 Multilabel Reader (manufactured by PerkinElmer) was used to measure the inhibitory activity according to the instructions attached to the kit. did.
具体的には、希釈調製したFAM-Cyclic-3’, 5’-GMPを25μLずつ各ウェルに添加した。「Blank」に25μLずつPDEバッファーを添加した。次いで、前述のように準備した抽出物600mgとジメチルスルホキシド20 mLとを混合して抽出物含有溶液を得た後、抽出物含有溶液5μLと滅菌水495μLを混合してサンプル溶液（抽出物濃度300μg/mL）とした。サンプル溶液（「Test」のウェル）またはサンプル溶媒（「Blank」、「Substrate control」、「Positive control」のウェル）を、各ウェルに5μL添加した。次いで、「Blank」と「Substrate control」のウェルに20μLずつPDEアッセイバッファーを添加した。希釈調製したPDE5Aを「Test」、「Positive control」のウェルに20 μLずつ添加した（200 pg/反応ウェル）。 25℃で1時間反応させた。希釈調製したBinding agentを100μLずつ各ウェルに添加し、25℃で30分間強く振とうしながら反応させた。プレートリーダーで蛍光偏光を測定した（Excitation：475-495 nm、Emission：518-538 nm）。「Blank」値をそれぞれの測定値から減じ、蛍光偏光値を算出した。また、IC50測定にはサンプル溶液の濃度を段階的に減少させて阻害率が50%になるサンプル濃度を求めた。
Specifically, 25 μL of diluted FAM-Cyclic-3 ′ and 5′-GMP were added to each well. 25 μL of PDE buffer was added to “Blank”. Next, 600 mg of the extract prepared as described above and 20 mL of dimethyl sulfoxide were mixed to obtain an extract-containing solution, and then 5 μL of the extract-containing solution and 495 μL of sterilized water were mixed to obtain a sample solution (extract concentration 300 μg). / mL). 5 μL of sample solution (“Test” well) or sample solvent (“Blank”, “Substrate control”, “Positive control” well) was added to each well. Next, 20 μL of PDE assay buffer was added to each of the “Blank” and “Substratestcontrol” wells. 20 μL of diluted PDE5A was added to each well of “Test” and “Positive control” (200 μg / reaction well). The reaction was allowed to proceed at 25 ° C for 1 hour. 100 μL of the diluted Binding agent was added to each well and reacted at 25 ° C. with strong shaking for 30 minutes. Fluorescence polarization was measured with a plate reader (Excitation: 475-495 nm, Emission: 518-538 nm). The “Blank” value was subtracted from each measured value to calculate the fluorescence polarization value. For IC50 measurement, the sample concentration at which the inhibition rate was 50% was determined by decreasing the concentration of the sample solution stepwise.
３．結果
結果を表１に示す。表１にはIC50値を示す。 3. The results are shown in Table 1. Table 1 shows IC50 values.
結果を表１に示す。表１にはIC50値を示す。 3. The results are shown in Table 1. Table 1 shows IC50 values.
表１から明らかなように、クロショウガでは、そのIC50値（μg/mL）は50を上回った。これに対して、実施例１～１５に示す植物の抽出物ではいずれも一層優れたPDE5活性阻害作用が認められ、これはクロショウガの阻害作用を大きく上回るものであった。
As is clear from Table 1, the IC50 value (μg / mL) of black ginger exceeded 50. In contrast, the plant extracts shown in Examples 1 to 15 all showed an even more excellent inhibitory effect on PDE5 activity, which far exceeded the inhibitory effect of black ginger.
このことから、PDEに対して活性阻害作用を有していることが従来知られている植物であるクロショウガよりも、前記植物の加工物によれば、より効果的にPDE5の活性を阻害できることが確認された。
From this, it is possible to inhibit the activity of PDE5 more effectively according to the processed product of the plant than black ginger, which is a plant known to have an activity inhibiting activity on PDE. Was confirmed.
試験例２
１．測定手順
前記試験例で準備した実施例１、４、５及び１０の抽出物、比較例の抽出物、ならびに対照として水を用いて、ラット組織中の環状グアノシン一リン酸（cGMP）量を測定した。 Test example 2
1. Measurement Procedure Using the extracts of Examples 1, 4, 5 and 10 prepared in the above test examples, the extract of the comparative example, and water as a control, the amount of cyclic guanosine monophosphate (cGMP) in rat tissue was measured. did.
１．測定手順
前記試験例で準備した実施例１、４、５及び１０の抽出物、比較例の抽出物、ならびに対照として水を用いて、ラット組織中の環状グアノシン一リン酸（cGMP）量を測定した。 Test example 2
1. Measurement Procedure Using the extracts of Examples 1, 4, 5 and 10 prepared in the above test examples, the extract of the comparative example, and water as a control, the amount of cyclic guanosine monophosphate (cGMP) in rat tissue was measured. did.
本測定には、SD系雄ラット（体重約250g/匹）、cGMP ELISA kit（ADI-900-014、エンゾライフサイエンス社製）、PerkinElmer EnVision 2102 Multilabel Reader（パーキンエルマー社製）を用いた。
For this measurement, SD male rats (weight approximately 250 g / animal), cGMP ELISA kit (ADI-900-014, manufactured by Enzo Life Science), PerkinElmer EnVision 2102 Multilabel reader (manufactured by PerkinElmer) were used.
具体的には、前記抽出物2gと蒸留水8mLとを混合し、前記抽出物含有投与液（500mg/2mL/kg体重）を各投与の直前に調製した。得られた投与液を、試験開始0時間及び24時間後に、ゾンデでラットの胃内に投与した（n=8）。試験開始25時間後に麻酔下でラットの陰茎を摘出し、これを液体窒素を用いて凍結保存した。cGMP ELISA kitに記載されている方法に従って、陰茎組織中のcGMP量を測定した。なお、対照として、抽出物含有投与液に代えて蒸留水を用いる以外は、同様にして胃内に投与し、陰茎組織中のcGMP量を測定した。
Specifically, 2 g of the extract and 8 mL of distilled water were mixed, and the extract-containing administration liquid (500 mg / 2 mL / kg body weight) was prepared immediately before each administration. The obtained administration solution was administered into the stomach of rats with a sonde at 0 and 24 hours after the start of the test (n = 8). 25 hours after the start of the test, the penis of the rat was removed under anesthesia and stored frozen using liquid nitrogen. The amount of cGMP in the penile tissue was measured according to the method described in cGMP ELISA kit. As a control, except that distilled water was used instead of the extract-containing administration solution, administration was carried out in the stomach in the same manner, and the amount of cGMP in the penile tissue was measured.
２．結果
結果を表２に示す。 2. The results are shown in Table 2.
結果を表２に示す。 2. The results are shown in Table 2.
表２から明らかなように、クロショウガ投与時のcGMP量は、蒸留水投与時のcGMP量を多少上回る程度であった。これに対して、実施例１、４、５及び１０の抽出物投与時のcGMP量は、クロショウガ投与時の２倍程度か２倍を大きく上回った。
As is clear from Table 2, the amount of cGMP at the time of administration of black ginger was slightly higher than the amount of cGMP at the time of administration of distilled water. On the other hand, the amount of cGMP at the time of administration of the extracts of Examples 1, 4, 5 and 10 was about twice or more than that at the time of administration of black ginger.
このように、実施例１、４、５及び１０の加工物において得られる値は、クロショウガにおいて得られる値を上回ったことから、実施例１、４、５及び１０の加工物によれば、ＰＤＥ５の活性や局所血流低下に起因する疾患をより効果的に予防または改善できることが確認された。
Thus, since the values obtained in the workpieces of Examples 1, 4, 5 and 10 exceeded the values obtained in black ginger, according to the workpieces of Examples 1, 4, 5 and 10. It was confirmed that diseases caused by PDE5 activity and local blood flow reduction can be prevented or improved more effectively.
また、前記試験例１の結果から明らかなように、PDE5の活性阻害作用の点で、実施例２、３、６～９及び１１～１５の加工物はクロショウガを大きく上回っており、このことから、実施例２、３、６～９及び１１～１５の加工物も、PDE5活性や局所血流低下に起因する疾患をより効果的に予防または改善できることが確認された。
Further, as is clear from the results of Test Example 1, the processed products of Examples 2, 3, 6-9 and 11-15 are significantly higher than black ginger in terms of PDE5 activity inhibitory action. From the results, it was confirmed that the processed products of Examples 2, 3, 6 to 9, and 11 to 15 can more effectively prevent or improve diseases caused by PDE5 activity and local blood flow reduction.
Claims (13)
- キイチゴ属（Rubus）、ザクロ属（Punica）、シモツケソウ属（Filipendula）、ヤマモモ属（Myrica）、エウゲニア属（Eugenia）、サルスベリ属（Lagerstroemia）、モモタマナ属（Terminalia）、アカミノキ属（Haematoxylon）、ソバカズラ属（Fallopia）及びカギカズラ属（Uncaria）からなる群より選択される少なくとも１つの植物の加工物を含有する、ホスホジエステラーゼ５活性阻害用組成物。 Rubus, Punica, Filipendula, Myrica, Eugenia, Lagerstroemia, Momardana (Terminalia), Haematoxylon, Buckwheat A composition for inhibiting phosphodiesterase 5 activity, comprising a processed product of at least one plant selected from the group consisting of (Fallopia) and Uncaria.
- キイチゴ属に属する植物が、ヒマラヤブラックベリー（Rubus armeniacus Focke）、セイヨウヤブイチゴ（Rubus fruticosus）及びアメリカイチゴ（Rubus strigosus）からなる群より選択される少なくとも１つである、請求項１に記載の組成物。 2. The composition according to claim 1, wherein the plant belonging to the genus Rubus is at least one selected from the group consisting of Himalayan blackberries (Rubus armeniacus Focke), Yabusu strawberries (Rubus fruticosus) and American strawberries (Rubus strigosus). object.
- ザクロ属に属する植物が、ザクロ（Punica granatum）である、請求項１に記載の組成物。 The composition according to claim 1, wherein the plant belonging to the genus Pomegranate is pomegranate (Punicaungranatum).
- シモツケソウ属に属する植物が、セイヨウナツユキソウ（Filipendula ulmaria）である、請求項１に記載の組成物。 The composition according to claim 1, wherein the plant belonging to the genus Pleurotus is Filipendula ulmaria.
- ヤマモモ属に属する植物が、シロコヤマモモ（Myrica cerifera）及びヤマモモ（Myrica rubura）からなる群より選択される少なくとも１つである、請求項１に記載の組成物。 The composition according to claim 1, wherein the plant belonging to the genus Corpus is at least one selected from the group consisting of Myrica cerifera and Myrica rubura.
- エウゲニア属に属する植物が、タチバナアデク（Eugenia uniflora）及びクローブ（Eugenia aromaticum）からなる群より選択される少なくとも１つである、請求項１に記載の組成物。 The composition according to claim 1, wherein the plant belonging to the genus Eugenia is at least one selected from the group consisting of Eugeniaugeuniflora and clove (Eugenia aromaticum).
- サルスベリ属に属する植物が、バナバ（Lagerstroemia speciosa）である、請求項１に記載の組成物。 The composition according to claim 1, wherein the plant belonging to the genus Crape myrtle is banaba (Lagerstroemia speciosa).
- モモタマナ属に属する植物が、モモタマナ（Terminalia catappa）及びセイタカミロバラン（Terminalia bellirica）からなる群より選択される少なくとも１つである、請求項１に記載の組成物。 The composition according to claim 1, wherein the plant belonging to the genus Momotamana is at least one selected from the group consisting of Momotamana (Terminalia catappa) and Seitakamibaran (Terminalia bellirica).
- アカミノキ属に属する植物が、アカミノキ（Haematoxylon campechianum）である、請求項１に記載の組成物。 The composition according to claim 1, wherein the plant belonging to the genus Redwood is Redwood (Haematoxylon campechianum).
- ソバカズラ属に属する植物が、イタドリ（Fallopia japonica）である、請求項１に記載の組成物。 The composition according to claim 1, wherein the plant belonging to the genus Buckwheat is a Japanese knotweed (Fallopia japonica).
- カギカズラ属に属する植物が、キャッツクロー（Uncaria guianensis）である、請求項１に記載の組成物。 The composition according to claim 1, wherein the plant belonging to the genus Kakazura is cats claw (Uncaria guianensis).
- 陰茎勃起機能、下部尿路機能障害、前立腺肥大及び肺高血圧症からなる群より選択される少なくとも１種の予防または改善用である、請求項１～１１のいずれかに記載の組成物。 The composition according to any one of claims 1 to 11, which is used for prevention or amelioration of at least one selected from the group consisting of penile erection function, lower urinary tract dysfunction, prostatic hypertrophy and pulmonary hypertension.
- 食品組成物、医薬組成物または飼料組成物である、請求項１～１２のいずれかに記載の組成物。 The composition according to any one of claims 1 to 12, which is a food composition, a pharmaceutical composition or a feed composition.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201780081426.6A CN110167571A (en) | 2016-12-28 | 2017-12-22 | Composition is used in the inhibition of 5 type phosphodiesterase activities |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2016256466A JP7058939B2 (en) | 2016-12-28 | 2016-12-28 | Composition for inhibiting phosphodiesterase 5 activity |
| JP2016-256466 | 2016-12-28 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2018123908A1 true WO2018123908A1 (en) | 2018-07-05 |
Family
ID=62707535
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/JP2017/046245 WO2018123908A1 (en) | 2016-12-28 | 2017-12-22 | Composition for inhibiting phosphodiesterase-5 activity |
Country Status (3)
| Country | Link |
|---|---|
| JP (1) | JP7058939B2 (en) |
| CN (2) | CN113559159A (en) |
| WO (1) | WO2018123908A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR3122990A1 (en) | 2021-05-20 | 2022-11-25 | Patrinove | Extract of plant with crassulacean acid metabolism for use in the treatment of erectile dysfunction |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP7278734B2 (en) * | 2018-09-28 | 2023-05-22 | 小林製薬株式会社 | Ellagic acid-containing composition |
| KR102211313B1 (en) * | 2019-01-17 | 2021-02-04 | 경희대학교 산학협력단 | A composition for preventing or treating prostatic hyperplasia comprising a mixed extract of Curcumae Radix and Syzygii Flos |
| WO2021106857A1 (en) * | 2019-11-29 | 2021-06-03 | 小林製薬株式会社 | Composition for preventing or relieving uresiesthesia stress, and composition for improving sleep |
| WO2021106856A1 (en) * | 2019-11-29 | 2021-06-03 | 小林製薬株式会社 | Composition for improving urinary tract function and composition for improving blood flow in bladder |
| JP7368340B2 (en) * | 2020-11-13 | 2023-10-24 | 金氏高麗人参株式会社 | Composition for inhibiting phosphodiesterase 5 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2003183122A (en) * | 2001-12-21 | 2003-07-03 | Ichimaru Pharcos Co Ltd | Agent for inhibiting activity of collagenase |
| KR20140101520A (en) * | 2013-02-11 | 2014-08-20 | 주식회사한국전통의학연구소 | A pharmaceutical composition for improving generative of male and treating infertility |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR100462173B1 (en) * | 2004-06-08 | 2004-12-16 | 안국약품 주식회사 | A composition for prevention and treatment of urinary incontinence |
| ITMI20050068A1 (en) * | 2005-01-21 | 2005-04-22 | Ignazio Abbruzzo | PASTA DENTIFRICIA COMPOSED MAINLY BY A COMMON PLANT RUBUS FRUTICOSUS WHICH PARTS OF IT CONTAIN AN ACTIVE PRINCIPLE THAT FIGHTS THE DENTAL CARIES GIVES THE HEALTH OF THE GUMS AND THE CLEANING OF THE TEETH |
| WO2014126269A1 (en) * | 2013-02-12 | 2014-08-21 | 주식회사 한국전통의학연구소 | Pharmaceutical composition for improving male sexual function and for treating infertility |
| CN103520618B (en) * | 2013-10-21 | 2015-08-26 | 孟庆坤 | A kind of pharmaceutical composition for the treatment of erection disturbance and preparation method thereof and pharmaceutical applications |
-
2016
- 2016-12-28 JP JP2016256466A patent/JP7058939B2/en active Active
-
2017
- 2017-12-22 CN CN202110993090.9A patent/CN113559159A/en active Pending
- 2017-12-22 CN CN201780081426.6A patent/CN110167571A/en active Pending
- 2017-12-22 WO PCT/JP2017/046245 patent/WO2018123908A1/en active Application Filing
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2003183122A (en) * | 2001-12-21 | 2003-07-03 | Ichimaru Pharcos Co Ltd | Agent for inhibiting activity of collagenase |
| KR20140101520A (en) * | 2013-02-11 | 2014-08-20 | 주식회사한국전통의학연구소 | A pharmaceutical composition for improving generative of male and treating infertility |
Non-Patent Citations (2)
| Title |
|---|
| GAIRE, R. ET AL.: "The biology of Canadian weeds. 154. Himalayan blackberry", CANADIAN JOURNAL OF PLANT SCIENCE, vol. 95, no. 3, May 2015 (2015-05-01), pages 557 - 570, XP055516867 * |
| ZHAO, C. ET AL.: "What is the role of unripe rubus coreanus extract on penile erection?", PHYTOTHERAPY RESEARCH, vol. 25, 1 June 2012 (2012-06-01), pages 1046 - 1053, XP018505049 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR3122990A1 (en) | 2021-05-20 | 2022-11-25 | Patrinove | Extract of plant with crassulacean acid metabolism for use in the treatment of erectile dysfunction |
Also Published As
| Publication number | Publication date |
|---|---|
| CN110167571A (en) | 2019-08-23 |
| JP7058939B2 (en) | 2022-04-25 |
| JP2018108946A (en) | 2018-07-12 |
| CN113559159A (en) | 2021-10-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| WO2018123908A1 (en) | Composition for inhibiting phosphodiesterase-5 activity | |
| KR102211814B1 (en) | Novel extracts of Cynara scolymus, Coffea spp. and Olea europaea for the treatment of metabolic syndrome | |
| KR101522273B1 (en) | A composition comprising the extract of Curcuma aromatica SALISB for preventing and treating benign prostatic hyperplasia | |
| US7279184B2 (en) | Methods and compositions comprising Ilex | |
| JP5264107B2 (en) | Composition having antioxidative action | |
| JP2003048844A (en) | Urease activity inhibitor | |
| KR101624704B1 (en) | Pharmaceutical composition and food composition for prevention, treatment or improvement of hair loss or benign prostatic hyperplasia | |
| KR102002298B1 (en) | Compositions for preventing, ameliorating or treating hyperuricemia or metabolic disorders associated with hyperuricemia comprising herbal extracts | |
| WO2018134848A1 (en) | Dietary supplements for inhibiting pde5 and increasing cgmp levels | |
| JP7371161B2 (en) | Composition for inhibiting phosphodiesterase 5 activity | |
| JP7331190B2 (en) | Composition for inhibiting phosphodiesterase 5 activity | |
| Sharmaine et al. | Xanthine Oxidase Inhibitory Activity of Methanolic Extract of Alternanthera sessilis | |
| KR20180044194A (en) | Composition for improving male sexual function using ginsenoside compound K and a maca extract | |
| JP5171080B2 (en) | Composition having antioxidative action | |
| JP2022040231A (en) | Xanthine oxydase activity inhibitory composition | |
| Shah et al. | Formulation and Evaluation of Antidiabetic and Antihyperlipidemic Activities of Polyherbal Formulation in Streptozotocin induced diabetic rat | |
| JP7254974B2 (en) | Composition for inhibiting xanthine oxidase activity | |
| WO2021261341A1 (en) | Composition for inhibiting phosphodiesterase 5 activity and improving erectile function | |
| Raafat et al. | Phytochemical and Biological Evaluation of Ultrasound-Assisted Spray Dried Lonicera etrusca for Potential Management of Diabetes. | |
| JP2006016340A (en) | Blood uric acid level reduction agent having extract of punica granatum l. as active ingredient | |
| KR102153830B1 (en) | Complex extracts for easing Hangover and improving liver function and preparation method of the same | |
| JPWO2005056031A1 (en) | Lipase inhibitor | |
| JP5264106B2 (en) | Composition having antioxidative action | |
| Idreess et al. | Turmeric: An important medicinal plant in the treatment of many diseases: A review Study | |
| JP2019178080A (en) | Edible composition and vascular endothelial function improver for enhancing production of nitric oxide in serum, promoting improvement of antioxidant function in liver and promoting serum triglyceride lowering function, containing black soybean seed coat extract and piper longum extract as essential ingredients |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 17888748 Country of ref document: EP Kind code of ref document: A1 |
|
| NENP | Non-entry into the national phase |
Ref country code: DE |
|
| 122 | Ep: pct application non-entry in european phase |
Ref document number: 17888748 Country of ref document: EP Kind code of ref document: A1 |