CN110167571A - Composition is used in the inhibition of 5 type phosphodiesterase activities - Google Patents
Composition is used in the inhibition of 5 type phosphodiesterase activities Download PDFInfo
- Publication number
- CN110167571A CN110167571A CN201780081426.6A CN201780081426A CN110167571A CN 110167571 A CN110167571 A CN 110167571A CN 201780081426 A CN201780081426 A CN 201780081426A CN 110167571 A CN110167571 A CN 110167571A
- Authority
- CN
- China
- Prior art keywords
- composition
- plant
- myrica
- belonging
- rubus
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 78
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 title claims abstract description 40
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 title claims abstract description 40
- 230000000694 effects Effects 0.000 title claims abstract description 30
- 230000005764 inhibitory process Effects 0.000 title abstract description 7
- 241000196324 Embryophyta Species 0.000 claims abstract description 72
- 241000219433 Myrica Species 0.000 claims abstract description 28
- 238000003754 machining Methods 0.000 claims abstract description 25
- 235000016622 Filipendula ulmaria Nutrition 0.000 claims abstract description 19
- 241000266331 Eugenia Species 0.000 claims abstract description 18
- 241000350160 Haematoxylum Species 0.000 claims abstract description 17
- 229940023569 palmate Drugs 0.000 claims abstract description 16
- 241000532927 Lagerstroemia Species 0.000 claims abstract description 15
- 241001534869 Terminalia Species 0.000 claims abstract description 15
- 241001092459 Rubus Species 0.000 claims abstract description 14
- 241001083505 Punica Species 0.000 claims abstract description 13
- 240000001341 Reynoutria japonica Species 0.000 claims abstract description 11
- 235000018167 Reynoutria japonica Nutrition 0.000 claims abstract description 11
- PFTAWBLQPZVEMU-DZGCQCFKSA-N (+)-catechin Chemical compound C1([C@H]2OC3=CC(O)=CC(O)=C3C[C@@H]2O)=CC=C(O)C(O)=C1 PFTAWBLQPZVEMU-DZGCQCFKSA-N 0.000 claims abstract description 10
- 244000089265 zong er cha Species 0.000 claims abstract description 10
- 241000157352 Uncaria Species 0.000 claims abstract description 6
- 241001289522 Fallopia Species 0.000 claims abstract description 5
- 241001092073 Filipendula Species 0.000 claims abstract description 5
- 235000013399 edible fruits Nutrition 0.000 claims description 20
- 244000308505 Filipendula ulmaria Species 0.000 claims description 18
- 235000009330 Terminalia Nutrition 0.000 claims description 13
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 11
- 235000014360 Punica granatum Nutrition 0.000 claims description 10
- 244000274911 Myrica cerifera Species 0.000 claims description 9
- 235000009134 Myrica cerifera Nutrition 0.000 claims description 9
- 241001600036 Rubus armeniacus Species 0.000 claims description 9
- 244000172730 Rubus fruticosus Species 0.000 claims description 9
- 244000277583 Terminalia catappa Species 0.000 claims description 9
- 235000009319 Terminalia catappa Nutrition 0.000 claims description 9
- 230000006870 function Effects 0.000 claims description 9
- 241000683228 Uncaria guianensis Species 0.000 claims description 8
- 235000011472 cat’s claw Nutrition 0.000 claims description 8
- 235000013305 food Nutrition 0.000 claims description 8
- 210000002307 prostate Anatomy 0.000 claims description 8
- 241000167854 Bourreria succulenta Species 0.000 claims description 6
- 235000013673 European blackberry Nutrition 0.000 claims description 6
- 235000014629 Myrica faya Nutrition 0.000 claims description 6
- 244000132436 Myrica rubra Species 0.000 claims description 6
- 241000205407 Polygonum Species 0.000 claims description 6
- 235000021028 berry Nutrition 0.000 claims description 6
- 235000019693 cherries Nutrition 0.000 claims description 6
- 244000223014 Syzygium aromaticum Species 0.000 claims description 5
- 235000016639 Syzygium aromaticum Nutrition 0.000 claims description 5
- 235000003095 Vaccinium corymbosum Nutrition 0.000 claims description 5
- 244000078534 Vaccinium myrtillus Species 0.000 claims description 5
- 235000017537 Vaccinium myrtillus Nutrition 0.000 claims description 5
- 235000021014 blueberries Nutrition 0.000 claims description 5
- 230000009986 erectile function Effects 0.000 claims description 5
- 208000002815 pulmonary hypertension Diseases 0.000 claims description 5
- 210000001635 urinary tract Anatomy 0.000 claims description 5
- 206010020880 Hypertrophy Diseases 0.000 claims description 4
- 244000294611 Punica granatum Species 0.000 claims description 4
- 240000003813 Eugenia uniflora Species 0.000 claims description 3
- 235000013420 Eugenia uniflora Nutrition 0.000 claims description 3
- 244000198896 Lagerstroemia speciosa 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
- 150000001875 compounds Chemical class 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
- 244000061544 Filipendula vulgaris Species 0.000 abstract 1
- 101150098694 PDE5A gene Proteins 0.000 abstract 1
- 239000000284 extract Substances 0.000 description 65
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 20
- 235000019441 ethanol Nutrition 0.000 description 18
- 238000000034 method Methods 0.000 description 18
- 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 15
- ZOOGRGPOEVQQDX-UHFFFAOYSA-N cyclic GMP Natural products O1C2COP(O)(=O)OC2C(O)C1N1C=NC2=C1NC(N)=NC2=O ZOOGRGPOEVQQDX-UHFFFAOYSA-N 0.000 description 15
- 239000000706 filtrate Substances 0.000 description 14
- 239000000843 powder Substances 0.000 description 14
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-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
- 239000000401 methanolic extract Substances 0.000 description 10
- 239000002904 solvent Substances 0.000 description 10
- 239000003795 chemical substances by application Substances 0.000 description 9
- 238000000605 extraction Methods 0.000 description 9
- 241000219991 Lythraceae Species 0.000 description 8
- 230000002401 inhibitory effect Effects 0.000 description 8
- 230000017531 blood circulation Effects 0.000 description 7
- 239000003814 drug Substances 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- 241001465754 Metazoa Species 0.000 description 6
- 201000010099 disease Diseases 0.000 description 6
- 239000004615 ingredient Substances 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 239000002994 raw material Substances 0.000 description 6
- 239000002023 wood Substances 0.000 description 6
- 238000001035 drying Methods 0.000 description 5
- -1 granula subtilis Substances 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 239000003826 tablet Substances 0.000 description 5
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 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
- 238000005259 measurement Methods 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 238000000638 solvent extraction Methods 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- 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
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 238000000354 decomposition reaction Methods 0.000 description 3
- 238000010790 dilution Methods 0.000 description 3
- 239000012895 dilution Substances 0.000 description 3
- 239000012153 distilled water Substances 0.000 description 3
- 230000006872 improvement Effects 0.000 description 3
- 210000004072 lung Anatomy 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- 239000012488 sample solution Substances 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 229940058015 1,3-butylene glycol Drugs 0.000 description 2
- AXPZIVKEZRHGAS-UHFFFAOYSA-N 3-benzyl-5-[(2-nitrophenoxy)methyl]oxolan-2-one Chemical compound [O-][N+](=O)C1=CC=CC=C1OCC1OC(=O)C(CC=2C=CC=CC=2)C1 AXPZIVKEZRHGAS-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 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
- 238000008157 ELISA kit Methods 0.000 description 2
- 101000988412 Homo sapiens cGMP-specific 3',5'-cyclic phosphodiesterase Proteins 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 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
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 238000007605 air drying Methods 0.000 description 2
- 239000007767 bonding agent Substances 0.000 description 2
- 235000019437 butane-1,3-diol Nutrition 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 238000005520 cutting process Methods 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 238000002875 fluorescence polarization Methods 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 210000003899 penis Anatomy 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 239000002590 phosphodiesterase V inhibitor Substances 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- 230000004648 relaxation of smooth muscle Effects 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 239000004575 stone Substances 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 150000005846 sugar alcohols Polymers 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 230000002485 urinary effect Effects 0.000 description 2
- 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
- NMYLSLKWQQWWSC-GWTDSMLYSA-N 2-amino-9-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-3h-purin-6-one;phosphoric acid Chemical compound OP(O)(O)=O.C1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O NMYLSLKWQQWWSC-GWTDSMLYSA-N 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 241000221032 Combretaceae Species 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 241000628997 Flos Species 0.000 description 1
- 239000001828 Gelatine Substances 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 241000219926 Myrtaceae Species 0.000 description 1
- 241000209094 Oryza Species 0.000 description 1
- 241000009328 Perro Species 0.000 description 1
- 241000219050 Polygonaceae Species 0.000 description 1
- 244000292697 Polygonum aviculare Species 0.000 description 1
- 235000006386 Polygonum aviculare Nutrition 0.000 description 1
- 241001107098 Rubiaceae Species 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 241000282898 Sus scrofa Species 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000001785 acacia senegal l. willd gum Substances 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
- 150000001413 amino acids Chemical class 0.000 description 1
- 238000001949 anaesthesia Methods 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 230000001741 anti-phlogistic effect Effects 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
- 238000003149 assay kit Methods 0.000 description 1
- 235000013361 beverage Nutrition 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000005253 cladding Methods 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 210000005226 corpus cavernosum Anatomy 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 238000005138 cryopreservation Methods 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 150000002012 dioxanes Chemical class 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 230000004064 dysfunction Effects 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
- 230000002255 enzymatic effect Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 239000000469 ethanolic extract Substances 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
- 239000003337 fertilizer Substances 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000007888 film coating Substances 0.000 description 1
- 238000009501 film coating Methods 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 235000013376 functional food Nutrition 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 238000002523 gelfiltration Methods 0.000 description 1
- 239000003349 gelling agent Substances 0.000 description 1
- 239000003292 glue Substances 0.000 description 1
- 239000008187 granular material Substances 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
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 230000006651 lactation Effects 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 230000008345 muscle blood flow Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000000419 plant extract Substances 0.000 description 1
- 239000011505 plaster Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 210000001147 pulmonary artery Anatomy 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 239000001575 punica granatum l. bark extract Substances 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 239000007940 sugar coated tablet Substances 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 238000000194 supercritical-fluid extraction Methods 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 230000001228 trophic effect Effects 0.000 description 1
- 210000003708 urethra Anatomy 0.000 description 1
- 238000009777 vacuum freeze-drying Methods 0.000 description 1
- 230000002792 vascular Effects 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
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 239000000080 wetting agent 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
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)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Microbiology (AREA)
- Medical Informatics (AREA)
- Alternative & Traditional Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Polymers & Plastics (AREA)
- Urology & Nephrology (AREA)
- Food Science & Technology (AREA)
- Zoology (AREA)
- Reproductive Health (AREA)
- Nutrition Science (AREA)
- Animal Husbandry (AREA)
- Physiology (AREA)
- Gynecology & Obstetrics (AREA)
- Endocrinology (AREA)
- Pulmonology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Molecular Biology (AREA)
- Medicines Containing Plant Substances (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
- Fodder In General (AREA)
Abstract
The active new composition of PDE5 is able to suppress the purpose of the present invention is to provide a kind of.A kind of 5 type phosphodiesterase activities inhibition composition, contains the machining object of at least one kind of plant in rubus (Rubus), Punica (Punica), palmate meadowsweet category (Filipendula), Myrica(Myrica) (Myrica), Eugenia (Eugenia), Lagerstroemia (Lagerstroemia), Terminalia (Terminalia), Haematoxylon (Haematoxylon), fleece-flower root category (Fallopia) and wild gambier (Uncaria).
Description
Technical field
The present invention relates to 5 type phosphodiesterase activity inhibition compositions.
Background technique
Phosphodiesterase (phosphodiesterase, PDE) is hydrolyzing cyclic GMP (cGMP), ring-type AMP (cAMP)
There are many families in mammals in enzyme.
Wherein, 5 type phosphodiesterases (PDE5) are primarily involved in the decomposition of cGMP.CGMP is played as intracellular second messenger
Effect, makes smooth muscle relaxation, and blood flow increases.Therefore, by inhibiting PDE5 activity, smooth muscle relaxation can be made and increase blood flow.
As the medicament using the effect, it is currently known PDE5 inhibitor, it has been known that there is with silaenafil for the medicament of representative
Pharmaceuticals etc. of the citrate as effective component.PDE5 inhibitor inhibits the decomposition of cGMP by inhibition PDE5 activity, from
And increase regional flow, therefore, for reduction, bladder and the function reduction of prostate, the high blood of lung for improving telotism ability
It presses the purpose of symptom as disease and is used.
Additionally, it is known that for example black ginger is able to suppress PDE activity (patent document 1).
Existing technical literature
Patent document
Patent document 1: Japanese Patent Laid-Open 2013-224326 bulletin
Summary of the invention
Problems to be solved by the invention
The active new composition of PDE5 is able to suppress the purpose of the present invention is to provide a kind of.For solving the side of project
Method
The present inventor has made intensive studies the above subject, as a result, it has been found that being belonged to outstanding using following plants
Hook category (Rubus), Punica (Punica), palmate meadowsweet category (Filipendula), Myrica(Myrica) (Myrica), Eugenia
(Eugenia), Lagerstroemia (Lagerstroemia), Terminalia (Terminalia), Haematoxylon (Haematoxylon), what
The plant of tuber of multiflower knotweed category (Fallopia) or wild gambier (Uncaria) is able to suppress PDE5 activity.
The present invention is based on the opinion, completes by further inquiring into repeatedly, carries out disclosure to it below.
A kind of 5 type phosphodiesterase activities of item 1. inhibit to use compositions, wherein containing selected from rubus (Rubus), stone
Pomegranate category (Punica), palmate meadowsweet category (Filipendula), Myrica(Myrica) (Myrica), Eugenia (Eugenia), Lagerstroemia
(Lagerstroemia), Terminalia (Terminalia), Haematoxylon (Haematoxylon), fleece-flower root category (Fallopia)
With the machining object of at least one kind of plant in wild gambier (Uncaria).
2. compositions as described in item 1 of item, wherein the plant for belonging to rubus is selected from Himalaya blackberry, blueberry (Rubus
Armeniacus Focke), in European black berry (Rubus fruticosus) and the red certain kind of berries in North America (Rubus strigosus) extremely
It is a kind few.
3. compositions as described in item 1 of item, wherein the plant for belonging to Punica is pomegranate (Punicagranatum).
4. compositions as described in item 1 of item, wherein belong to the plant of palmate meadowsweet category for rotation fruit palmate meadowsweet (Filipendula
ulmaria)。
5. compositions as described in item 1 of item, wherein the plant for belonging to Myrica(Myrica) is selected from candleberry (Myrica
Cerifera at least one kind of) and in red bayberry (Myrica rubura).
6. compositions as described in item 1 of item, wherein the plant for belonging to Eugenia is selected from flat cherry (Eugenia
Uniflora at least one kind of) and in cloves (Eugenia aromaticum).
7. compositions as described in item 1 of item, wherein the plant for belonging to Lagerstroemia is banaba (Lagerstroemia
speciosa)。
8. compositions as described in item 1 of item, wherein the plant for belonging to Terminalia is selected from TERMINALIA CATAPPA (Terminalia
Catappa) and adjoin at least one kind of in Li Le (Terminalia bellirica).
9. compositions as described in item 1 of item, wherein the plant for belonging to Haematoxylon is to adopt wood (Haematoxylon
campechianum)。
10. compositions as described in item 1 of item, wherein the plant for belonging to fleece-flower root category is polygonum cuspidate (Fallopia
japonica)。
11. compositions as described in item 1 of item, wherein the plant for belonging to wild gambier is uncaria guianensis (Uncaria
guianensis)。
Composition of the item 12. as described in any one of item 1~11, is used to prevent or improve selected from telotism function
At least one kind of prevention or improvement in energy, low urinary tract function obstacle, hypertrophy of the prostate and pulmonary hypertension disease.
Composition described in item 13. any one of 1~12 is food compositions, medical composition or feed group
Close object.
Invention effect
In accordance with the invention it is possible to inhibit PDE5 active.Therefore, composition of the invention can be to prevent or improve cGMP points
Disease caused by the adjoint blood flow of solution reduces, such as penile erectile function, low urinary tract function obstacle, hypertrophy of the prostate, lung
It is used for the purpose of disease as vascular hypertension.
Specific embodiment
The present invention provides 5 type phosphodiesterase activities and inhibits to use composition, contains selected from rubus (Rubus), stone
Pomegranate category (Punica), palmate meadowsweet category (Filipendula), Myrica(Myrica) (Myrica), Eugenia (Eugenia), Lagerstroemia
(Lagerstroemia), Terminalia (Terminalia), Haematoxylon (Haematoxylon), fleece-flower root category (Fallopia)
With the machining object of at least one kind of plant in wild gambier (Uncaria).
In composition of the invention, as effective component by comprising above-mentioned plant machining object raw material, respectively can be with
It enumerates and belongs to rubus, Punica, palmate meadowsweet category, Myrica(Myrica), Eugenia, Lagerstroemia, Terminalia, Haematoxylon, He Shou
The plant of any of crow category, wild gambier.
Rubus belongs to rosaceae, as the plant for belonging to the category, may be exemplified Himalaya blackberry, blueberry (Rubus
Armeniacus Focke), European black berry (Rubus fruticosus), the red certain kind of berries in North America (Rubus strigosus) etc., but this
It invents without being limited thereto.
Punica belongs to Lythraceae, as the plant for belonging to the category, may be exemplified pomegranate (Punica granatum)
Deng however, the present invention is not limited thereto.
Palmate meadowsweet category belongs to rosaceae, as the plant for belonging to the category, may be exemplified rotation fruit palmate meadowsweet (Filipendula
Ulmaria) etc., however, the present invention is not limited thereto.
Myrica(Myrica) belongs to Myruca ceas, as the plant for belonging to the category, may be exemplified candleberry (Myrica cerifera),
Red bayberry (Myrica rubura) etc., however, the present invention is not limited thereto.
Eugenia belongs to Myrtaceae, as the plant for belonging to the category, may be exemplified flat cherry (Eugenia
Uniflora), cloves (Eugenia aromaticum) etc., however, the present invention is not limited thereto.
Lagerstroemia belongs to Lythraceae, as the plant for belonging to the category, may be exemplified banaba (Lagerstroemia
Speciosa) etc., however, the present invention is not limited thereto.
Terminalia belongs to combretaceae, as the plant for belonging to the category, may be exemplified TERMINALIA CATAPPA (Terminalia
Catappa), adjoin Li Le (Terminalia bellirica) etc., however, the present invention is not limited thereto.
Haematoxylon belongs to pulse family, as the plant for belonging to the category, may be exemplified and adopts wood (Haematoxylon
Campechianum) etc., however, the present invention is not limited thereto.
Fleece-flower root category belongs to polygonaceae, as the plant for belonging to the category, may be exemplified polygonum cuspidate (Fallopia japonica)
Deng however, the present invention is not limited thereto.
Wild gambier belongs to Rubiaceae, as the plant for belonging to the category, may be exemplified uncaria (Uncaria guianensis)
Deng however, the present invention is not limited thereto.
These can be used singly or in combination of two or more.
As long as these plant is just not particularly limited using position, may be exemplified leaf, stem, fruit, flower, bud,
Branch, dry, bark, root, bud, seed, kind skin etc. suitably select according to each plant.It is preferred that illustrate leaf, stem, fruit,
Bark, root, dry, bud etc., more preferably illustrate, and rubus is leaf, fruit, and Punica is fruit, and palmate meadowsweet category is
Leaf, stem, Myrica(Myrica) are bark, and Eugenia is fruit, bud, and Lagerstroemia is leaf, and Terminalia is fruit, adopt wood
Category is to do, and fleece-flower root category is stem, leaf, and wild gambier is root, stem, leaf.As position is used, can be used alone,
Two or more can be applied in combination.
The machining object of plant in the present invention can enumerate the crushed material, dried object, extraction of the plant as above-mentioned raw materials
Object etc..
Crushed material is as long as being crushed above-mentioned plant using the grinder well known in the art such as jet mill without spy
It does not limit.
Dried object is not particularly limited as long as by above-mentioned plant drying, can pass through sun dehydration, far infrared
The conventionally known drying means such as irradiation, drying machine (heated-air drying, cold air drying, vacuum freeze-drying etc.) obtain.In addition, as dry
Amount of moisture in dry object, preferably 10 weight % are hereinafter, be more preferably 8 weight % or less.The form of dried object in the present invention
It does not limit, dried object, crushed material of dried object of plant itself etc..Xeraphium mince can by with above-mentioned crushing
The same method of object crushes dried object to obtain.In addition, being also able to use will be as raw material as the dried object in the present invention
Dried object obtained from plant is dried after fermentation process, enzymatic treatment.
The manufacturing method (extracting method) of extract and extraction conditions etc. are not particularly limited, according to conventionally known method
?.For example, after can above-mentioned plant being cut off, crushed or be dried as former state or as needed etc., using squeezing or
Solvent extraction and obtain extract.As the method for solvent extraction, using the method being known in the art, such as can
Utilize the conventionally known extracting methods such as water (including warm water, hot water) extraction, alcohol extracting, means of supercritical extraction.
When carrying out solvent extraction, as solvent it can be cited for example that water；The lower alcohols such as methanol, ethyl alcohol, isopropanol, the third two
The alcohols (anhydrous or hydrous) of the polyalcohols such as alcohol, 1,3 butylene glycol etc.；The ketones such as acetone, diethyl ether, dioxanes, acetonitrile,
The esters such as ethyl acetate, dimethylbenzene, benzene, chloroform etc..It is preferably water, lower alcohol, 1,3-BDO etc. as solvent, more preferably
For water, methanol, ethyl alcohol, 1,3-BDO, more preferably water, methanol, hydrous ethanol.These solvents can be used alone,
Two or more can also be applied in combination.
In the present invention, the extract obtained by such solvent extraction especially can be known as solvent extractable matter.And
And referred to as water extract when for example can use water as solvent as described above, use alcohol extracting referred to as rudimentary when lower alcohols
Object is taken, using referred to as ethanol extract etc. when ethyl alcohol, but the present invention is not limited by this.
Obtained extract can directly be used with the state of original sample, with powdered, graininess after can also being dried
Deng solid form use.Furthermore it is possible to according to needing to refine obtained extract, concentration, separating high live
Property be partially separated processing etc..The present invention is not so limited, and as refinement treatment, can be enumerated filtering, used ion friendship
Change processing as the absorption of resin or carbon column etc., decoloration.In addition, as concentration, it can be using evaporator etc. often
Rule method.In addition, the separating treatment as separation high activity partially, it can be solidifying using gel filtration, adsorption treatment, silica
Separating treatment well known to glue column chromatography method, HPLC (High performance liquid chromatography) etc..
In addition, for example, (may further be its dried object, refinement treatment object, dense by extract that such as foregoing manner obtains
Contracting processed material, high activity partially) supply frozen dried and the method that carries out powdered, it can be according to needing to add dextrin, corn
The excipient such as starch, Arabic gum, the conventionally known method such as method for carrying out powdered by spray drying treatment carry out powder
Endization, as the extract being used in the present invention.Furthermore it is possible to by the extract according to needing to be dissolved in water, ethyl alcohol etc. after
It uses.
As the extract of above-mentioned plant, preferably illustrate will it is dry as the plant of raw material (using position), crush and/or
It after cutting, is extracted using preferred solvent, the extract being obtained by filtration, in addition, the extract obtained in this way is further
Extract obtained from being dried.Those skilled in the art are suitably extracted according to each plant or using position, are extracted
Object can be obtained by following methods, but the present invention is not limited by this, and this method is, to the every 100g of plant as raw material,
More preferably to be impregnated using 1~50 liter of Extraction solvent to the dried object of the plant, crushed material and/or the cutting every 100g of object,
Under arbitrary temperature (such as 15~90 DEG C), according to needing to be stirred on one side, any duration is carried out on one side (such as 10 minutes
~24 hours) extraction, be then filtered.As the machining object of the plant in the present invention, preferred plant extract (including its
Dried object etc.).
The machining object of plant used in the present invention is also possible to commercially available product, can also be for commercially available product further progress
The product of the processing such as dry.
The machining object of the plant obtained in this way can be used singly or in combination of two or more.
For the content of the machining object of the above-mentioned plant in composition of the invention, as long as in the composition containing upper
The machining object of plant is stated, as long as effect of the invention can be obtained, there is no limit.In composition, above-mentioned plant adds
Work object may be exemplified in terms of dried object conversion containing 0 weight % is more than, and preferably be illustrated as more than 0 weight % and lower than 100 weights
% is measured, 0.001~99 weight % is more preferably illustrated as.When using machining object of more than two kinds, total amount meets the value.Machining object
Dried object can by by machining object carry out frozen dried and obtain.Frozen dried is by using general evaporator
It is concentrated under reduced pressure and is lyophilized under vacuum state.More detailed processing sequence is according to aftermentioned embodiment.
In addition, in the present compositions, the administering (intake) of the machining object of above-mentioned plant is as long as amount can play this
The effect of invention, there is no particular limitation, according to the physique of object (animal subject), the age, symptom, be applicable in form, use
Purpose, degree of the effect of expectation etc. are appropriately configured.Measured as administering in 1 day (intake), with weight 60kg at
People (is converted) as benchmark, the machining object of above-mentioned plant with dry weight in the total amount, is preferably illustrated as 0.001~8000mg,
It is more preferably illustrated as 0.01~5000mg, but the present invention is not limited by this.Composition of the invention can carry out single daily
It administers (intake), can also repeatedly be administered (intake).
Composition of the invention is oral or non-oral.There is no limit for the form of composition of the invention, according to
Purpose is appropriately configured.As the form of composition of the invention, liquor, emulsion, suspension, syrup may be exemplified
The liquids form such as agent, extract, spirit, elixir；Powder, granule, granula subtilis, tablet, pill, capsule (including hard capsule,
Soft capsule), containing agent, masticatory, gel, white shape, paste, this shape that rubs, sheet, liquid form the semisolids such as lyophilized products or
Solid states；In addition, aerosol agent etc., attaching the various forms such as agent, plaster, percutaneous absorption type preparation.
In addition, itself and water etc. can be used in mixed way, when composition for example of the invention is solid states in addition, this hair
Bright composition is also possible to the dosage form of slow-release.In addition, for example tablet can according to need be made be applied with it is conventionally known
The tablet of agent skin, such as sugar coated tablet, gelatine glaze piece, enteric coated tablets, film coating piece or double-layer tablets, multilayer tablet.
In addition, also there is no limit be appropriately configured the usage mode of composition of the invention according to purpose.As
The usage mode of composition of the invention, can be as food compositions (including beverage, health functional food (including specific guarantor
Strong food, trophic function food, the food of display functionality, health care product etc.), sufferer food), medical composition, feed
In addition composition can be used as the use such as additive of food compositions, medical composition, feed etc..
Composition of the invention is manufactured according to the conventionally known conventional means of above-mentioned various forms, usage mode etc.
Can, according to needs, pharmaceutically acceptable ingredient can also be mixed, acceptable ingredient, comestible composition in perfuming cosmetic science
Such any ingredient etc. manufactures.As the arbitrary ingredient, may be exemplified solvent, (water, methanol, ethyl alcohol, isopropanol etc. are low
Grade alcohol；Alcohols such as the polyalcohols such as propylene glycol, 1,3 butylene glycol (anhydrous or aqueous) etc.), excipient, disintegrating agent,
Diluent, fragrance, colorant, sweetener, corrigent, suspension, wetting agent, emulsifier, solubilizer, dispersing agent, delays lubricant
Electuary, bonding agent, impregnation-accelerator, stabilizer, swelling agent, preservative, tackifier, pH regulator, surfactant, cladding
Agent, sorbefacient, adsorbent, filler, antioxidant, antiphlogistic, freshener, envelope forming agent, gelling agent, amino
Acid, vitamin, enzyme, various nutritional ingredients etc..These can be used singly or in combination of two or more.
In the present invention, there is no limit may be exemplified the lactation other than the mankind, the mankind to the object (animal subject) of composition
Animal.As the mammal other than the mankind, 5 type phosphodiesterases can be enumerated and play the animal for promoting the decomposition of cGMP, it can
To illustrate the animals such as mouse, rat, cavy, rabbit, dog, cat, monkey, pig, ox, horse, preferably illustration mouse, rat, cavy, rabbit, dog,
The animals such as monkey.
Using composition of the invention, using the machining object of above-mentioned plant as effective component, it is able to suppress 5 type di-phosphate esters
Enzyme (PDE5) activity.Therefore, the present invention provides a kind of characterized by the machining object for using above-mentioned plant, PDE5 activity suppression use
The manufacturing method of composition.In addition, the present invention also provides the processes for including the machining object for preparing above-mentioned plant, the suppression of PDE5 activity
The system manufacturing method of composition.In addition, the present invention provides a kind of characterized by the machining object for using above-mentioned plant, PDE5 work
Property suppressing method.
PDE5 activity is able to suppress using composition of the invention in this way.As a result, in accordance with the invention it is possible to inhibit cGMP's
Decompose, can for prevent or improve PDE5 activity or caused by the reduction of local institute's blood flow for the purpose of disease due to use the present invention
Composition.
Therefore, composition of the invention is for preventing or improving penile erectile function, low urinary tract function obstacle, prostate fertilizer
Greatly, pulmonary hypertension disease etc. is useful, but the present invention is not limited by this.For example, making smooth muscle using PDE5 inhibiting effect
Relaxation, thus, it is possible to increase the blood flow of corpora cavernosa penis, it is possible to realize the improvement of penile erectile function in this way, by increasing uropoiesis
The blood flow of system, it is possible to realize the improvement of lower urinary tract obstacle, and by increasing the blood flow of prostate and urethra, it is possible to realize prostates
Loose alleviation, by increasing the blood flow of lung tissue, it is possible to realize the reductions of pulmonary arterial pressure.
Composition of the invention can also be preferably applied to take notice of the object of function of male, take notice of urinary function as a result,
Object etc..
In addition, composition of the invention can as PDE5 activity inhibitor, penile erectile function (not complete) medicine, under
Urinary dysfunction medicine, hypertrophy of the prostate medicine, pulmonary hypertension disease medicine (especially pulmonary artery pulmonary hypertension
Disease) etc. use.
Embodiment
In the following, by illustrative embodiments come the present invention will be described in more detail, but the invention is not limited to these examples.
Test example 1
1. the machining object of plant
Using plant shown in table 1 as raw material, the extract of each plant is prepared.Specifically, for embodiment 1,5,9
With 10, it is prepared for extract according to following step, commercially available product has been used for other embodiments.
Embodiment 1: Himalaya blackberry, blueberry
The dried object 50g of the leaf of Himalaya blackberry, blueberry is crushed, the water of 1000ml is added, is implemented with 80 DEG C, 1 hour
Extraction process.Obtained extract is filtered using MIRACLOTH (MERCK MILLIPORE corporation), will be eliminated not
The filtrate of soluble components is lyophilized, and Himalaya blackberry extract (extracting dried object 7.9g) has been obtained.
Embodiment 2: European black berry
The extract of the leaf of European black berry has been used (Nippon Shinyaku Co., Ltd.'s system especially produces, powder dried object).This
Extract is to crush the dried object of the leaf of European black berry, and addition methanol extracts, and is carried out to obtained extract
Filter, obtained from the filtrate for eliminating insoluble composition is lyophilized.
Embodiment 3: the red certain kind of berries in North America
Extract (Nippon Shinyaku Co., Ltd.'s system, especially production, the powder drying of the leaf and fruit of the red certain kind of berries in North America are used
Object).This extract is to crush the dried object of the leaf of the red certain kind of berries in North America and fruit, and addition methanol extracts, to what is obtained
Extract is filtered, obtained from the filtrate for eliminating insoluble composition is lyophilized.
Embodiment 4: pomegranate
Extract (trade name Pomegranate Peel Extract end, the fragrant industrial system of Sakae, the powder drying of the pericarp of pomegranate are used
Object).
Embodiment 5: rotation fruit palmate meadowsweet
The dried object 40g of the stem and leaf that revolve fruit palmate meadowsweet is crushed, the water of 1000ml is added, with 80 DEG C, 1 hour reality
Extraction process is applied.Obtained extract is filtered using MIRACLOTH (MERCK MILLIPORE society system), will be eliminated not
The filtrate of soluble components is lyophilized, and rotation fruit palmate meadowsweet extract (extracting dried object 9.9g) has been obtained.
Embodiment 6: candleberry
The extract of the bark of candleberry has been used (Nippon Shinyaku Co., Ltd.'s system especially produces, powder dried object).This
Extract is to crush the dried object of the bark of candleberry, and addition methanol extracts, and is carried out to obtained extract
Filter, obtained from the filtrate for eliminating insoluble composition is lyophilized.
Embodiment 7: red bayberry
The extract of the bark of red bayberry has been used (Nippon Shinyaku Co., Ltd.'s system especially produces, powder dried object).Originally it mentions
Taking object is to crush the dried object of the bark of red bayberry, and addition methanol extracts, and is filtered to obtained extract, will
Eliminate insoluble composition filtrate be lyophilized obtained from.
Embodiment 8: flat cherry
The extract of the fruit of flat cherry has been used (Nippon Shinyaku Co., Ltd.'s system especially produces, powder dried object).This
Extract is to crush the dried object of the fruit of flat cherry, and addition methanol extracts, and is carried out to obtained extract
Filter, obtained from the filtrate for eliminating insoluble composition is lyophilized.
Embodiment 9: cloves
The dried object 50g of the bud of cloves is crushed, the water of 1000ml is added, implements extraction 80 DEG C, 1 hour
Processing.Obtained extract is filtered using MIRACLOTH (MERCK MILLIPORE society system), is eliminated by freeze-drying insoluble
Property ingredient filtrate, obtained Flos Caryophylli extract (extract dried object 10.1g).
Embodiment 10: banaba
The dried object 60g of banaba leaf is crushed, the ethyl alcohol (the mass ratio 1:1 of water and ethyl alcohol) of 50 mass % is added
900ml implements extraction process in 12 hours with 25 DEG C.Obtained extract is used into MIRACLOTH (MERCK MILLIPORE
Society's system) it filters, after distillation removal ethyl alcohol in the filtrate for eliminate insoluble composition, it is lyophilized, has obtained banaba and mentioned
Take object (extracting dried object 8.9g).
Embodiment 11: TERMINALIA CATAPPA
The extract of the fruit of TERMINALIA CATAPPA has been used (Nippon Shinyaku Co., Ltd.'s system especially produces, powder dried object).This
Extract is to crush the dried object of the fruit of TERMINALIA CATAPPA, and addition methanol extracts, and is carried out to obtained extract
Filter, obtained from the filtrate for eliminating insoluble composition is lyophilized.
Embodiment 12: adjoin Li Le
The extract for adjoining the fruit of Li Le has been used (Nippon Shinyaku Co., Ltd.'s system especially produces, powder dried object).This
Extract is to crush the dried object for the fruit for adjoining Li Le, and addition methanol extracts, and is carried out to obtained extract
Filter, obtained from the filtrate for eliminating insoluble composition is lyophilized.
Embodiment 13: wood is adopted
The tree thyraden for adopting wood has been used (Nippon Shinyaku Co., Ltd.'s system especially produces, powder dried object).Originally it mentions
Taking object is to crush the dried object for the trunk for adopting wood, and addition methanol extracts, and is filtered to obtained extract, will
Eliminate insoluble composition filtrate be lyophilized obtained from.
Embodiment 14: polygonum cuspidate
The stem of polygonum cuspidate and the extract of leaf have been used (Nippon Shinyaku Co., Ltd.'s system especially produces, powder dried object).This
Extract is to crush the dried object of the stem of polygonum cuspidate and leaf, and addition methanol extracts, and is carried out to obtained extract
Filter, obtained from the filtrate for eliminating insoluble composition is lyophilized.
Embodiment 15: uncaria guianensis
The root of uncaria guianensis, extract (Nippon Shinyaku Co., Ltd.'s system, especially production, the powder of stem and leaf are used
Dried object).This extract is to crush the dried object of the root of uncaria guianensis, stem and leaf, and addition methanol extracts, right
Obtained extract is filtered, obtained from the filtrate for eliminating insoluble composition is lyophilized.
Comparative example: black ginger
The extract (Shang Pin Ming ?ginger extract-P, ORYZA oiling system, powder dried object) of the rhizome of black ginger is used.
Black ginger is to be currently known the plant inhibited for phosphodiesterase (PDE).
2. the measurement of 5 type phosphodiesterase (PDE) inhibitory activity
Each extract for preparing in above-mentioned 1. is determined for the inhibitory activity (n=3) of PDE5.In this measurement, make
With PDE5A Assay Kit (#60350) (BPS BIOSCIENCE corporation), 96 orifice plates, automatic pipettor,
PerkinElmer EnVision 2102Multilabel Reader (PERKINELMER society system), it is subsidiary according to kit
Specification determines inhibitory activity.
Specifically, the FAM-Cyclic-3 ' of dilution preparation, 5 '-GMP are respectively added into 25 μ L into each hole." right
According to " in be respectively added to the PDE buffer of 25 μ L.Later, the extract 600mg and diformazan for being mixed with and preparing such as foregoing manner is added
After solution containing extract obtained from base sulfoxide 20mL, the 5 μ L of solution containing extract and 495 μ L of aqua sterilisa is mixed
It closes, sample solution is made (extract concentrations are 300 μ g/mL).5 μ L sample solution (hole of " test ") or sample are added into each hole
Product solvent (" blank control ", " Substrate controls ", the hole of " positive control ").Then, to " blank control " and " Substrate controls "
The PDE analysis buffer of 20 μ L is respectively added in hole.By dilution preparation PDE5A to " test ", " positive control " hole in respectively add
Add 20 μ L (200pg/ reacting hole).It is reacted 1 hour at 25 DEG C.The bonding agent of dilution preparation is respectively added into 100 μ L into each hole,
It is acutely vibrated 30 minutes at 25 DEG C on one side, makes its reaction on one side.Using microplate reader determine fluorescence polarization (Excitation:
475-495nm, Emission:518-538nm)." blank control " value is subtracted from each measured value, calculates fluorescence polarization value.Separately
Outside, IC50 measurement is the sample concentration acquired when inhibiting rate reaches 50% by periodically reducing the concentration of sample solution.
3. result
Show the result in table 1.IC50 value is shown in table 1.
[table 1]
It can be defined according to table 1, the IC50 value (μ g/mL) of black ginger is greater than 50.In contrast, shown in embodiment 1~15
The extract of plant all confirmed more excellent PDE5 activity inhibition, and the effect of the extract of these plants is all much high
In the inhibiting effect of black ginger.
It is possible thereby to confirm, relative to the black ginger of plant to the active inhibiting effect of PDE being currently known, utilization is above-mentioned
The machining object of plant can more effectively inhibit PDE5 active.
Test example 2
1. measuring operation order
Use the extract of the embodiment 1,4,5 and 10 prepared in above-mentioned test case, the extract and work of comparative example
For the water of control, cyclic guanosine-phosphoric acid (cGMP) amount in rat tissue is determined.
SD system male rat (weight about 250g/ is only), cGMP ELISA kit (ADI-900- have been used in this measurement
014, Enzo Life Sciences corporation), PerkinElmer EnVision 2102Multilabel Reader
(PerkinElmer corporation).
Specifically, said extracted object 2g and distilled water 8mL is mixed, prepares above-mentioned contain before it will carry out each administering
There is the administering liquid (500mg/2mL/kg weight) of extract.After test starts 0 hour and 24 hours, the administering liquid that will be obtained is sharp
With feeder administering to (n=8) in the stomach of rat.After test starts 25 hours, the penis of rat is taken out under anaesthesia, by it
Cryopreservation is carried out with liquid nitrogen.The cGMP in penile tissue is determined by the method recorded in cGMP ELISA kit
Amount.It should be noted that using distilled water to replace as the administering liquid containing extract, in addition to this, similarly as control
Administering in stomach is carried out, the cGMP amount in penile tissue is determined.
2. result
Show the result in table 2.
[table 2]
It can be defined according to table 2, cGMP amount when cGMP amount when administering black ginger is than administering distilled water is more slightly higher
Left and right.In contrast, cGMP amount when administering the extract of embodiment 1,4,5 and 10 is 2 times or so or remote when administering black ginger
Greater than 2 times.
It is worth in this way, value obtained in machining object from embodiment 1,4,5 and 10 is greater than obtained in the black ginger, thereby confirms that
More effectively it can prevent or improve since PDE5 activity, regional flow reduce using the machining object of embodiment 1,4,5 and 10
Caused disease.
In addition, can be defined according to the result of above-mentioned test example 1, from the viewpoint of PDE5 activity inhibition, implement
The machining object of example 2,3,6~9 and 11~15 is much higher than black ginger, it is possible thereby to confirm, embodiment 2,3,6~9 and 11~15 adds
Work object also more effectively can prevent or improve the disease caused by reducing PDE5 activity, regional flow.
Claims (13)
1. a kind of 5 type phosphodiesterase activities inhibit to use composition, it is characterised in that:
Containing selected from rubus (Rubus), Punica (Punica), palmate meadowsweet category (Filipendula), Myrica(Myrica)
(Myrica), Eugenia (Eugenia), Lagerstroemia (Lagerstroemia), Terminalia (Terminalia), Haematoxylon
(Haematoxylon), the machining object of fleece-flower root category (Fallopia) and at least one kind of plant in wild gambier (Uncaria).
2. composition as described in claim 1, it is characterised in that:
The plant for belonging to rubus is selected from Himalaya blackberry, blueberry (Rubus armeniacus Focke), European black berry
It is at least one kind of in the red certain kind of berries of (Rubus fruticosus) and North America (Rubus strigosus).
3. composition as described in claim 1, it is characterised in that:
The plant for belonging to Punica is pomegranate (Punica granatum).
4. composition as described in claim 1, it is characterised in that:
Belong to the plant of palmate meadowsweet category for rotation fruit palmate meadowsweet (Filipendula ulmaria).
5. composition as described in claim 1, it is characterised in that:
Belong to Myrica(Myrica) plant be in candleberry (Myrica cerifera) and red bayberry (Myrica rubura) extremely
It is a kind few.
6. composition as described in claim 1, it is characterised in that:
The plant for belonging to Eugenia is selected from flat cherry (Eugenia uniflora) and cloves (Eugenia aromaticum)
In it is at least one kind of.
7. composition as described in claim 1, it is characterised in that:
The plant for belonging to Lagerstroemia is banaba (Lagerstroemia speciosa).
8. composition as described in claim 1, it is characterised in that:
The plant for belonging to Terminalia is selected from TERMINALIA CATAPPA (Terminalia catappa) and adjoins Li Le (Terminalia
Bellirica at least one kind of in).
9. composition as described in claim 1, it is characterised in that:
The plant for belonging to Haematoxylon is to adopt wooden (Haematoxylon campechianum).
10. composition as described in claim 1, it is characterised in that:
The plant for belonging to fleece-flower root category is polygonum cuspidate (Fallopia japonica).
11. composition as described in claim 1, it is characterised in that:
The plant for belonging to wild gambier is uncaria guianensis (Uncaria guianensis).
12. the composition as described in any one of claim 1~11, it is characterised in that:
It is used to prevent or improve in penile erectile function, low urinary tract function obstacle, hypertrophy of the prostate and pulmonary hypertension disease
It is at least one kind of.
13. the composition as described in any one of claim 1~12, it is characterised in that:
It is food compositions, medical composition or fodder compound.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110993090.9A CN113559159A (en) | 2016-12-28 | 2017-12-22 | Composition for inhibiting type 5 phosphodiesterase activity |
Applications Claiming Priority (3)
| 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 | ||
| PCT/JP2017/046245 WO2018123908A1 (en) | 2016-12-28 | 2017-12-22 | Composition for inhibiting phosphodiesterase-5 activity |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202110993090.9A Division CN113559159A (en) | 2016-12-28 | 2017-12-22 | Composition for inhibiting type 5 phosphodiesterase activity |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN110167571A true CN110167571A (en) | 2019-08-23 |
Family
ID=62707535
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201780081426.6A Pending CN110167571A (en) | 2016-12-28 | 2017-12-22 | Composition is used in the inhibition of 5 type phosphodiesterase activities |
| CN202110993090.9A Pending CN113559159A (en) | 2016-12-28 | 2017-12-22 | Composition for inhibiting type 5 phosphodiesterase activity |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202110993090.9A Pending CN113559159A (en) | 2016-12-28 | 2017-12-22 | Composition for inhibiting type 5 phosphodiesterase activity |
Country Status (3)
| Country | Link |
|---|---|
| JP (1) | JP7058939B2 (en) |
| CN (2) | CN110167571A (en) |
| WO (1) | WO2018123908A1 (en) |
Families Citing this family (6)
| 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 |
| 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 |
| JPWO2021106857A1 (en) * | 2019-11-29 | 2021-06-03 | ||
| JP7368340B2 (en) * | 2020-11-13 | 2023-10-24 | 金氏高麗人参株式会社 | Composition for inhibiting phosphodiesterase 5 |
| FR3122990A1 (en) | 2021-05-20 | 2022-11-25 | Patrinove | Extract of plant with crassulacean acid metabolism for use in the treatment of erectile dysfunction |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1683547A1 (en) * | 2005-01-21 | 2006-07-26 | Ignazio Abbruzzo | Anticaries toothpaste containing Rubus Fruticosus for treating and cleaning teeth and/or gums |
| CN1964729B (en) * | 2004-06-08 | 2010-05-05 | 安国药品株式会社 | Composition for prevention and treatment of urinary incontinence |
| CN103520618A (en) * | 2013-10-21 | 2014-01-22 | 赵吉利 | Preparation method of okra plant viagra |
Family Cites Families (3)
| 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 |
| WO2014126269A1 (en) * | 2013-02-12 | 2014-08-21 | 주식회사 한국전통의학연구소 | Pharmaceutical composition for improving male sexual function and for treating infertility |
-
2016
- 2016-12-28 JP JP2016256466A patent/JP7058939B2/en active Active
-
2017
- 2017-12-22 CN CN201780081426.6A patent/CN110167571A/en active Pending
- 2017-12-22 CN CN202110993090.9A patent/CN113559159A/en active Pending
- 2017-12-22 WO PCT/JP2017/046245 patent/WO2018123908A1/en active Application Filing
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1964729B (en) * | 2004-06-08 | 2010-05-05 | 安国药品株式会社 | Composition for prevention and treatment of urinary incontinence |
| EP1683547A1 (en) * | 2005-01-21 | 2006-07-26 | Ignazio Abbruzzo | Anticaries toothpaste containing Rubus Fruticosus for treating and cleaning teeth and/or gums |
| CN103520618A (en) * | 2013-10-21 | 2014-01-22 | 赵吉利 | Preparation method of okra plant viagra |
Non-Patent Citations (4)
| Title |
|---|
| 向德军: "掌叶覆盆子提取物的温肾助阳作用研究", 《广东药学院学报》 * |
| 周凌燕: "虎杖口服液对慢性阻塞性肺疾病伴肺动脉高压患者的疗效观察", 《中国优秀硕士学位论文全文数据库，医药卫生科技辑》 * |
| 方玉春；等: "磷酸二酯酶5抑制剂研究进展", 《中国药学杂志》 * |
| 陈宇勒: "《家养药食两用花草》", 31 July 2015, 福建科学技术出版社 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN113559159A (en) | 2021-10-29 |
| JP2018108946A (en) | 2018-07-12 |
| WO2018123908A1 (en) | 2018-07-05 |
| JP7058939B2 (en) | 2022-04-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN110167571A (en) | Composition is used in the inhibition of 5 type phosphodiesterase activities | |
| WO2013100105A1 (en) | Maillard reaction inhibitor | |
| JP5842640B2 (en) | Phosphodiesterase 3 inhibitor | |
| JP2010209051A (en) | Fat absorption inhibitor | |
| Jha et al. | Phytochemical analysis and in vitro urolithiatic activity of Peltophorum pterocarpum leaves (DC) Baker | |
| JP2020033380A (en) | Anti-aging agent | |
| JP6024899B2 (en) | Unpleasant taste reduction method | |
| JP2006232781A (en) | Hypoglycemic composition comprising substance derived from bark of genus acacia | |
| DE10308298A1 (en) | Production of a plant preparation useful for treating cancer comprises extracting glucosinolates from plant material and enzymatically hydrolyzing the glucosinolates to isothiocyanates | |
| JP2015083564A (en) | Composition containing serenoa repens fruit extract and peucedanum japonicum extract | |
| JP2005336165A (en) | Saw palmetto extract composition and method for producing saw palmetto extract | |
| KR102604237B1 (en) | Composition for enhancing the bioavailability of fat-soluble vitamins | |
| JP5288832B2 (en) | Hyaluronidase inhibitor and composition containing the same | |
| JPH10179157A (en) | Chlorophyllase inhibitor, and food, feed and cosmetic containing the inhibitor | |
| JP2011074062A (en) | Anti-i type allergic agent | |
| JP2006016340A (en) | Blood uric acid level reduction agent having extract of punica granatum l. as active ingredient | |
| WO2018151334A1 (en) | Xanthine oxidase inhibitor and method for producing same | |
| JP7237998B2 (en) | Composition for inhibiting phosphodiesterase 5 activity | |
| JP7331190B2 (en) | Composition for inhibiting phosphodiesterase 5 activity | |
| HASSAN et al. | Effect of watery and alcoholic medicinal plants extractions on in-vitro ruminant | |
| JP6330120B1 (en) | Eating and drinking composition | |
| JP6099024B2 (en) | Phosphodiesterase 3 inhibitor | |
| JP2002114691A (en) | Active oxygen scavenger | |
| JP5264106B2 (en) | Composition having antioxidative action | |
| JP5265177B2 (en) | Composition for improving bowel movements containing acacia bark |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WD01 | Invention patent application deemed withdrawn after publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20190823 |