CN116056761A - 包含翅果连翘提取物作为活性成分的用于治疗雄激素受体相关疾病的药物组合物 - Google Patents
包含翅果连翘提取物作为活性成分的用于治疗雄激素受体相关疾病的药物组合物 Download PDFInfo
- Publication number
- CN116056761A CN116056761A CN202180053368.2A CN202180053368A CN116056761A CN 116056761 A CN116056761 A CN 116056761A CN 202180053368 A CN202180053368 A CN 202180053368A CN 116056761 A CN116056761 A CN 116056761A
- Authority
- CN
- China
- Prior art keywords
- extract
- samara
- androgen receptor
- isoquercetin
- fructus forsythiae
- 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
- 239000000284 extract Substances 0.000 title claims abstract description 94
- 108010080146 androgen receptors Proteins 0.000 title claims abstract description 92
- 201000010099 disease Diseases 0.000 title claims abstract description 43
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims abstract description 43
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 25
- 239000004480 active ingredient Substances 0.000 title claims abstract description 24
- 102000001307 androgen receptors Human genes 0.000 title claims abstract description 16
- OVSQVDMCBVZWGM-QSOFNFLRSA-N quercetin 3-O-beta-D-glucopyranoside Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=C(C=2C=C(O)C(O)=CC=2)OC2=CC(O)=CC(O)=C2C1=O OVSQVDMCBVZWGM-QSOFNFLRSA-N 0.000 claims abstract description 69
- OVSQVDMCBVZWGM-IDRAQACASA-N Hirsutrin Natural products O([C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1)C1=C(c2cc(O)c(O)cc2)Oc2c(c(O)cc(O)c2)C1=O OVSQVDMCBVZWGM-IDRAQACASA-N 0.000 claims abstract description 68
- FVQOMEDMFUMIMO-UHFFFAOYSA-N Hyperosid Natural products OC1C(O)C(O)C(CO)OC1OC1C(=O)C2=C(O)C=C(O)C=C2OC1C1=CC=C(O)C(O)=C1 FVQOMEDMFUMIMO-UHFFFAOYSA-N 0.000 claims abstract description 68
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 claims abstract description 66
- 208000004403 Prostatic Hyperplasia Diseases 0.000 claims abstract description 65
- OVSQVDMCBVZWGM-QCKGUQPXSA-N isoquercetin Natural products OC[C@@H]1O[C@@H](OC2=C(Oc3cc(O)cc(O)c3C2=O)c4ccc(O)c(O)c4)[C@H](O)[C@@H](O)[C@@H]1O OVSQVDMCBVZWGM-QCKGUQPXSA-N 0.000 claims abstract description 62
- 239000003098 androgen Substances 0.000 claims abstract description 39
- 201000004384 Alopecia Diseases 0.000 claims abstract description 14
- 206010060862 Prostate cancer Diseases 0.000 claims abstract description 12
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims abstract description 12
- 231100000360 alopecia Toxicity 0.000 claims abstract description 8
- 206010013990 dysuria Diseases 0.000 claims abstract description 8
- 230000014509 gene expression Effects 0.000 claims description 59
- 239000000203 mixture Substances 0.000 claims description 42
- 108010072866 Prostate-Specific Antigen Proteins 0.000 claims description 31
- 102000007066 Prostate-Specific Antigen Human genes 0.000 claims description 31
- 241000576429 Forsythia suspensa Species 0.000 claims description 29
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 27
- 230000011664 signaling Effects 0.000 claims description 21
- -1 C 6 Alcohols Chemical class 0.000 claims description 20
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 14
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 14
- 102000015694 estrogen receptors Human genes 0.000 claims description 13
- 108010038795 estrogen receptors Proteins 0.000 claims description 13
- 235000013305 food Nutrition 0.000 claims description 13
- 238000000034 method Methods 0.000 claims description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 12
- 239000002904 solvent Substances 0.000 claims description 12
- 239000003814 drug Substances 0.000 claims description 11
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 9
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 9
- 230000036541 health Effects 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 8
- 241000576821 Abeliophyllum distichum Species 0.000 claims description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 6
- 108010066551 Cholestenone 5 alpha-Reductase Proteins 0.000 claims description 6
- 108090001146 Nuclear Receptor Coactivator 1 Proteins 0.000 claims description 6
- 230000007730 Akt signaling Effects 0.000 claims description 5
- 239000012530 fluid Substances 0.000 claims description 5
- 235000013376 functional food Nutrition 0.000 claims description 5
- 101100534223 Caenorhabditis elegans src-1 gene Proteins 0.000 claims description 4
- 102000004966 Nuclear Receptor Coactivator 1 Human genes 0.000 claims description 4
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims description 3
- 239000003208 petroleum Substances 0.000 claims description 3
- 238000010171 animal model Methods 0.000 abstract description 28
- 230000002401 inhibitory effect Effects 0.000 abstract description 10
- 230000001225 therapeutic effect Effects 0.000 abstract description 9
- 230000001419 dependent effect Effects 0.000 abstract description 8
- 229940126585 therapeutic drug Drugs 0.000 abstract 1
- 102100032187 Androgen receptor Human genes 0.000 description 76
- 210000002307 prostate Anatomy 0.000 description 74
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 48
- MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 description 36
- 239000000469 ethanolic extract Substances 0.000 description 20
- 230000002829 reductive effect Effects 0.000 description 20
- 235000002639 sodium chloride Nutrition 0.000 description 20
- 235000013399 edible fruits Nutrition 0.000 description 19
- 235000019441 ethanol Nutrition 0.000 description 18
- 229960003604 testosterone Drugs 0.000 description 18
- NVKAWKQGWWIWPM-ABEVXSGRSA-N 17-β-hydroxy-5-α-Androstan-3-one Chemical compound C1C(=O)CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CC[C@H]21 NVKAWKQGWWIWPM-ABEVXSGRSA-N 0.000 description 17
- 230000000694 effects Effects 0.000 description 17
- 230000005764 inhibitory process Effects 0.000 description 17
- 238000004458 analytical method Methods 0.000 description 16
- 210000004027 cell Anatomy 0.000 description 16
- 229960003473 androstanolone Drugs 0.000 description 15
- 229940030486 androgens Drugs 0.000 description 13
- 150000003839 salts Chemical class 0.000 description 13
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 12
- 102000038030 PI3Ks Human genes 0.000 description 11
- 108091007960 PI3Ks Proteins 0.000 description 11
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 11
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 11
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 11
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 11
- 241001092040 Crataegus Species 0.000 description 10
- 235000009917 Crataegus X brevipes Nutrition 0.000 description 10
- 235000013204 Crataegus X haemacarpa Nutrition 0.000 description 10
- 235000009685 Crataegus X maligna Nutrition 0.000 description 10
- 235000009444 Crataegus X rubrocarnea Nutrition 0.000 description 10
- 235000009486 Crataegus bullatus Nutrition 0.000 description 10
- 235000017181 Crataegus chrysocarpa Nutrition 0.000 description 10
- 235000009682 Crataegus limnophila Nutrition 0.000 description 10
- 235000004423 Crataegus monogyna Nutrition 0.000 description 10
- 235000002313 Crataegus paludosa Nutrition 0.000 description 10
- 235000009840 Crataegus x incaedua Nutrition 0.000 description 10
- 102000006311 Cyclin D1 Human genes 0.000 description 10
- 108010058546 Cyclin D1 Proteins 0.000 description 10
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- PDMMFKSKQVNJMI-BLQWBTBKSA-N Testosterone propionate Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](OC(=O)CC)[C@@]1(C)CC2 PDMMFKSKQVNJMI-BLQWBTBKSA-N 0.000 description 10
- 229960004039 finasteride Drugs 0.000 description 10
- DBEPLOCGEIEOCV-WSBQPABSSA-N finasteride Chemical compound N([C@@H]1CC2)C(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H](C(=O)NC(C)(C)C)[C@@]2(C)CC1 DBEPLOCGEIEOCV-WSBQPABSSA-N 0.000 description 10
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 10
- 229960001712 testosterone propionate Drugs 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- 238000012790 confirmation Methods 0.000 description 9
- 241000555712 Forsythia Species 0.000 description 8
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 8
- 239000001768 carboxy methyl cellulose Substances 0.000 description 8
- 239000000463 material Substances 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 8
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 7
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 7
- 239000012153 distilled water Substances 0.000 description 7
- 229960001031 glucose Drugs 0.000 description 7
- 239000007924 injection Substances 0.000 description 7
- 238000002347 injection Methods 0.000 description 7
- 239000013641 positive control Substances 0.000 description 7
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 229920002472 Starch Polymers 0.000 description 6
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 6
- 229930006000 Sucrose Natural products 0.000 description 6
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 6
- 235000013361 beverage Nutrition 0.000 description 6
- 238000011161 development Methods 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 239000000796 flavoring agent Substances 0.000 description 6
- GXMWXESSGGEWEM-UHFFFAOYSA-N isoquercitrin Natural products OCC(O)C1OC(OC2C(Oc3cc(O)cc(O)c3C2=O)c4ccc(O)c(O)c4)C(O)C1O GXMWXESSGGEWEM-UHFFFAOYSA-N 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 229920000609 methyl cellulose Polymers 0.000 description 6
- 235000010981 methylcellulose Nutrition 0.000 description 6
- 239000001923 methylcellulose Substances 0.000 description 6
- 229960002900 methylcellulose Drugs 0.000 description 6
- 229920001223 polyethylene glycol Polymers 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- 230000008569 process Effects 0.000 description 6
- 235000018102 proteins Nutrition 0.000 description 6
- 102000004169 proteins and genes Human genes 0.000 description 6
- 108090000623 proteins and genes Proteins 0.000 description 6
- 210000002966 serum Anatomy 0.000 description 6
- 208000024891 symptom Diseases 0.000 description 6
- 238000001262 western blot Methods 0.000 description 6
- CWVRJTMFETXNAD-FWCWNIRPSA-N 3-O-Caffeoylquinic acid Natural products O[C@H]1[C@@H](O)C[C@@](O)(C(O)=O)C[C@H]1OC(=O)\C=C\C1=CC=C(O)C(O)=C1 CWVRJTMFETXNAD-FWCWNIRPSA-N 0.000 description 5
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 5
- NEJKEXUJCSYMCC-PXBUXKMDSA-N 5-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-3-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-7-[(2S,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxychromen-4-one Chemical compound C1=C(O)C(OC)=CC(C2=C(C(=O)C3=C(O)C=C(O[C@H]4[C@@H]([C@H](O)[C@@H](O)[C@H](C)O4)O)C=C3O2)O[C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)=C1 NEJKEXUJCSYMCC-PXBUXKMDSA-N 0.000 description 5
- PZIRUHCJZBGLDY-UHFFFAOYSA-N Caffeoylquinic acid Natural products CC(CCC(=O)C(C)C1C(=O)CC2C3CC(O)C4CC(O)CCC4(C)C3CCC12C)C(=O)O PZIRUHCJZBGLDY-UHFFFAOYSA-N 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- 102000004218 Insulin-Like Growth Factor I Human genes 0.000 description 5
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 5
- NEJKEXUJCSYMCC-AKTJOMHVSA-N Isorhamnetin 3-O-beta-glucopyranoside-7-O-alpha-rhamnopyranoside Natural products O(C)c1c(O)ccc(C2=C(O[C@H]3[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O3)C(=O)c3c(O)cc(O[C@H]4[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O4)cc3O2)c1 NEJKEXUJCSYMCC-AKTJOMHVSA-N 0.000 description 5
- NEJKEXUJCSYMCC-UHFFFAOYSA-N Isorhamnetin-3-O-glucosyl-7-O-rhamnoside Natural products C1=C(O)C(OC)=CC(C2=C(C(=O)C3=C(O)C=C(OC4C(C(O)C(O)C(C)O4)O)C=C3O2)OC2C(C(O)C(O)C(CO)O2)O)=C1 NEJKEXUJCSYMCC-UHFFFAOYSA-N 0.000 description 5
- CWVRJTMFETXNAD-KLZCAUPSSA-N Neochlorogenin-saeure Natural products O[C@H]1C[C@@](O)(C[C@@H](OC(=O)C=Cc2ccc(O)c(O)c2)[C@@H]1O)C(=O)O CWVRJTMFETXNAD-KLZCAUPSSA-N 0.000 description 5
- 240000006661 Serenoa repens Species 0.000 description 5
- 235000005318 Serenoa repens Nutrition 0.000 description 5
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 5
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 5
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 5
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 230000037396 body weight Effects 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- CWVRJTMFETXNAD-JUHZACGLSA-N chlorogenic acid Chemical compound O[C@@H]1[C@H](O)C[C@@](O)(C(O)=O)C[C@H]1OC(=O)\C=C\C1=CC=C(O)C(O)=C1 CWVRJTMFETXNAD-JUHZACGLSA-N 0.000 description 5
- 229940074393 chlorogenic acid Drugs 0.000 description 5
- 235000001368 chlorogenic acid Nutrition 0.000 description 5
- FFQSDFBBSXGVKF-KHSQJDLVSA-N chlorogenic acid Natural products O[C@@H]1C[C@](O)(C[C@@H](CC(=O)C=Cc2ccc(O)c(O)c2)[C@@H]1O)C(=O)O FFQSDFBBSXGVKF-KHSQJDLVSA-N 0.000 description 5
- BMRSEYFENKXDIS-KLZCAUPSSA-N cis-3-O-p-coumaroylquinic acid Natural products O[C@H]1C[C@@](O)(C[C@@H](OC(=O)C=Cc2ccc(O)cc2)[C@@H]1O)C(=O)O BMRSEYFENKXDIS-KLZCAUPSSA-N 0.000 description 5
- 239000003085 diluting agent Substances 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 238000000605 extraction Methods 0.000 description 5
- 235000019253 formic acid Nutrition 0.000 description 5
- 239000000499 gel Substances 0.000 description 5
- 239000008103 glucose Substances 0.000 description 5
- 239000008187 granular material Substances 0.000 description 5
- 239000003102 growth factor Substances 0.000 description 5
- 230000003676 hair loss Effects 0.000 description 5
- 238000003306 harvesting Methods 0.000 description 5
- 239000002035 hexane extract Substances 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 239000012528 membrane Substances 0.000 description 5
- 230000002018 overexpression Effects 0.000 description 5
- 239000003755 preservative agent Substances 0.000 description 5
- 239000010018 saw palmetto extract Substances 0.000 description 5
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 5
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 239000003381 stabilizer Substances 0.000 description 5
- 238000010186 staining Methods 0.000 description 5
- 235000019698 starch Nutrition 0.000 description 5
- 229940032147 starch Drugs 0.000 description 5
- 239000008107 starch Substances 0.000 description 5
- 239000005720 sucrose Substances 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 5
- 244000215068 Acacia senegal Species 0.000 description 4
- 102000007469 Actins Human genes 0.000 description 4
- 108010085238 Actins Proteins 0.000 description 4
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 4
- 241000196324 Embryophyta Species 0.000 description 4
- 108010010803 Gelatin Proteins 0.000 description 4
- 229920000084 Gum arabic Polymers 0.000 description 4
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 4
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 4
- 239000002202 Polyethylene glycol Substances 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 235000010489 acacia gum Nutrition 0.000 description 4
- 239000000205 acacia gum Substances 0.000 description 4
- 239000000654 additive Substances 0.000 description 4
- 230000004663 cell proliferation Effects 0.000 description 4
- 230000005754 cellular signaling Effects 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 239000000839 emulsion Substances 0.000 description 4
- 235000013355 food flavoring agent Nutrition 0.000 description 4
- 235000003599 food sweetener Nutrition 0.000 description 4
- 239000008273 gelatin Substances 0.000 description 4
- 229920000159 gelatin Polymers 0.000 description 4
- 235000019322 gelatine Nutrition 0.000 description 4
- 235000011852 gelatine desserts Nutrition 0.000 description 4
- 208000024963 hair loss Diseases 0.000 description 4
- 239000004615 ingredient Substances 0.000 description 4
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 4
- 239000008108 microcrystalline cellulose Substances 0.000 description 4
- 229940016286 microcrystalline cellulose Drugs 0.000 description 4
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 4
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 4
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 4
- 230000002335 preservative effect Effects 0.000 description 4
- 235000013772 propylene glycol Nutrition 0.000 description 4
- 210000005267 prostate cell Anatomy 0.000 description 4
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 4
- 235000010356 sorbitol Nutrition 0.000 description 4
- 239000000600 sorbitol Substances 0.000 description 4
- 229960002920 sorbitol Drugs 0.000 description 4
- 239000003765 sweetening agent Substances 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- 229940124597 therapeutic agent Drugs 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- 210000002700 urine Anatomy 0.000 description 4
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 3
- 239000002677 5-alpha reductase inhibitor Substances 0.000 description 3
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 3
- 102100021569 Apoptosis regulator Bcl-2 Human genes 0.000 description 3
- JMGZEFIQIZZSBH-UHFFFAOYSA-N Bioquercetin Natural products CC1OC(OCC(O)C2OC(OC3=C(Oc4cc(O)cc(O)c4C3=O)c5ccc(O)c(O)c5)C(O)C2O)C(O)C(O)C1O JMGZEFIQIZZSBH-UHFFFAOYSA-N 0.000 description 3
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 3
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 3
- 102000011632 Caseins Human genes 0.000 description 3
- 108010076119 Caseins Proteins 0.000 description 3
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 3
- 239000004375 Dextrin Substances 0.000 description 3
- 229920001353 Dextrin Polymers 0.000 description 3
- 102000009024 Epidermal Growth Factor Human genes 0.000 description 3
- 101800003838 Epidermal growth factor Proteins 0.000 description 3
- 101000971171 Homo sapiens Apoptosis regulator Bcl-2 Proteins 0.000 description 3
- 101000602926 Homo sapiens Nuclear receptor coactivator 1 Proteins 0.000 description 3
- 101000651467 Homo sapiens Proto-oncogene tyrosine-protein kinase Src Proteins 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- 239000004166 Lanolin Substances 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- 102100027384 Proto-oncogene tyrosine-protein kinase Src Human genes 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 235000010443 alginic acid Nutrition 0.000 description 3
- 229920000615 alginic acid Polymers 0.000 description 3
- 229910052783 alkali metal Inorganic materials 0.000 description 3
- 150000001340 alkali metals Chemical class 0.000 description 3
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 3
- 230000006399 behavior Effects 0.000 description 3
- 239000011230 binding agent Substances 0.000 description 3
- 150000001720 carbohydrates Chemical class 0.000 description 3
- 235000014633 carbohydrates Nutrition 0.000 description 3
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 3
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 3
- 229940105329 carboxymethylcellulose Drugs 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 235000019868 cocoa butter Nutrition 0.000 description 3
- 229940110456 cocoa butter Drugs 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- 235000019425 dextrin Nutrition 0.000 description 3
- 235000014113 dietary fatty acids Nutrition 0.000 description 3
- 239000007884 disintegrant Substances 0.000 description 3
- 229940116977 epidermal growth factor Drugs 0.000 description 3
- IVTMALDHFAHOGL-UHFFFAOYSA-N eriodictyol 7-O-rutinoside Natural products OC1C(O)C(O)C(C)OC1OCC1C(O)C(O)C(O)C(OC=2C=C3C(C(C(O)=C(O3)C=3C=C(O)C(O)=CC=3)=O)=C(O)C=2)O1 IVTMALDHFAHOGL-UHFFFAOYSA-N 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 239000000194 fatty acid Substances 0.000 description 3
- 229930195729 fatty acid Natural products 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 235000011187 glycerol Nutrition 0.000 description 3
- 210000003780 hair follicle Anatomy 0.000 description 3
- JQOAQUXIUNVRQW-UHFFFAOYSA-N hexane Chemical compound CCCCCC.CCCCCC JQOAQUXIUNVRQW-UHFFFAOYSA-N 0.000 description 3
- 239000001341 hydroxy propyl starch Substances 0.000 description 3
- 235000013828 hydroxypropyl starch Nutrition 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 235000019388 lanolin Nutrition 0.000 description 3
- 229940039717 lanolin Drugs 0.000 description 3
- 239000000314 lubricant Substances 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- 239000002207 metabolite Substances 0.000 description 3
- 230000027939 micturition Effects 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 239000006187 pill Substances 0.000 description 3
- 229920000136 polysorbate Polymers 0.000 description 3
- FDRQPMVGJOQVTL-UHFFFAOYSA-N quercetin rutinoside Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC=2C(C3=C(O)C=C(O)C=C3OC=2C=2C=C(O)C(O)=CC=2)=O)O1 FDRQPMVGJOQVTL-UHFFFAOYSA-N 0.000 description 3
- 235000005493 rutin Nutrition 0.000 description 3
- IKGXIBQEEMLURG-BKUODXTLSA-N rutin Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@@H]1OC[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](OC=2C(C3=C(O)C=C(O)C=C3OC=2C=2C=C(O)C(O)=CC=2)=O)O1 IKGXIBQEEMLURG-BKUODXTLSA-N 0.000 description 3
- ALABRVAAKCSLSC-UHFFFAOYSA-N rutin Natural products CC1OC(OCC2OC(O)C(O)C(O)C2O)C(O)C(O)C1OC3=C(Oc4cc(O)cc(O)c4C3=O)c5ccc(O)c(O)c5 ALABRVAAKCSLSC-UHFFFAOYSA-N 0.000 description 3
- 229960004555 rutoside Drugs 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 239000001632 sodium acetate Substances 0.000 description 3
- 235000017281 sodium acetate Nutrition 0.000 description 3
- 235000010413 sodium alginate Nutrition 0.000 description 3
- 239000000661 sodium alginate Substances 0.000 description 3
- 229940005550 sodium alginate Drugs 0.000 description 3
- 239000000375 suspending agent Substances 0.000 description 3
- 239000000454 talc Substances 0.000 description 3
- 229910052623 talc Inorganic materials 0.000 description 3
- 235000012222 talc Nutrition 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 210000001550 testis Anatomy 0.000 description 3
- 238000001946 ultra-performance liquid chromatography-mass spectrometry Methods 0.000 description 3
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 2
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
- 229920001817 Agar Polymers 0.000 description 2
- 239000005995 Aluminium silicate Substances 0.000 description 2
- 101100365087 Arabidopsis thaliana SCRA gene Proteins 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 241000283707 Capra Species 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 2
- 239000004386 Erythritol Substances 0.000 description 2
- UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 description 2
- 239000001856 Ethyl cellulose Substances 0.000 description 2
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 2
- 229930091371 Fructose Natural products 0.000 description 2
- 239000005715 Fructose Substances 0.000 description 2
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 2
- 241000546188 Hypericum Species 0.000 description 2
- 235000017309 Hypericum perforatum Nutrition 0.000 description 2
- 206010071289 Lower urinary tract symptoms Diseases 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- 108010051791 Nuclear Antigens Proteins 0.000 description 2
- 102000019040 Nuclear Antigens Human genes 0.000 description 2
- 102100037223 Nuclear receptor coactivator 1 Human genes 0.000 description 2
- 241000207834 Oleaceae Species 0.000 description 2
- 235000019483 Peanut oil Nutrition 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 2
- 108091008611 Protein Kinase B Proteins 0.000 description 2
- 101150105073 SCR1 gene Proteins 0.000 description 2
- 101100134054 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) NTG1 gene Proteins 0.000 description 2
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 2
- ABBQHOQBGMUPJH-UHFFFAOYSA-M Sodium salicylate Chemical compound [Na+].OC1=CC=CC=C1C([O-])=O ABBQHOQBGMUPJH-UHFFFAOYSA-M 0.000 description 2
- 235000021355 Stearic acid Nutrition 0.000 description 2
- 239000006180 TBST buffer Substances 0.000 description 2
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 2
- YKTSYUJCYHOUJP-UHFFFAOYSA-N [O--].[Al+3].[Al+3].[O-][Si]([O-])([O-])[O-] Chemical compound [O--].[Al+3].[Al+3].[O-][Si]([O-])([O-])[O-] YKTSYUJCYHOUJP-UHFFFAOYSA-N 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 210000004404 adrenal cortex Anatomy 0.000 description 2
- 239000008272 agar Substances 0.000 description 2
- 235000010419 agar Nutrition 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 239000000783 alginic acid Substances 0.000 description 2
- 229960001126 alginic acid Drugs 0.000 description 2
- 150000004781 alginic acids Chemical class 0.000 description 2
- 150000001342 alkaline earth metals Chemical class 0.000 description 2
- 235000012211 aluminium silicate Nutrition 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 230000027455 binding Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 239000001506 calcium phosphate Substances 0.000 description 2
- 229910000389 calcium phosphate Inorganic materials 0.000 description 2
- 235000011010 calcium phosphates Nutrition 0.000 description 2
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 2
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 2
- 239000004202 carbamide Substances 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 239000005018 casein Substances 0.000 description 2
- BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 description 2
- 235000021240 caseins Nutrition 0.000 description 2
- 235000010980 cellulose Nutrition 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 235000005687 corn oil Nutrition 0.000 description 2
- 239000002285 corn oil Substances 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- 235000012343 cottonseed oil Nutrition 0.000 description 2
- 239000002385 cottonseed oil Substances 0.000 description 2
- 238000004807 desolvation Methods 0.000 description 2
- 239000008121 dextrose Substances 0.000 description 2
- 230000003828 downregulation Effects 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 238000001962 electrophoresis Methods 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 description 2
- 235000019414 erythritol Nutrition 0.000 description 2
- 229940009714 erythritol Drugs 0.000 description 2
- 238000002481 ethanol extraction Methods 0.000 description 2
- 235000019325 ethyl cellulose Nutrition 0.000 description 2
- 229920001249 ethyl cellulose Polymers 0.000 description 2
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 2
- 229940093471 ethyl oleate Drugs 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 150000004665 fatty acids Chemical class 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 235000019634 flavors Nutrition 0.000 description 2
- 239000007850 fluorescent dye Substances 0.000 description 2
- 235000015203 fruit juice Nutrition 0.000 description 2
- 230000002496 gastric effect Effects 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 210000004209 hair Anatomy 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 2
- 238000003384 imaging method Methods 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 238000003780 insertion Methods 0.000 description 2
- 230000037431 insertion Effects 0.000 description 2
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 229940057995 liquid paraffin Drugs 0.000 description 2
- 239000006210 lotion Substances 0.000 description 2
- 239000007937 lozenge Substances 0.000 description 2
- 238000012423 maintenance Methods 0.000 description 2
- 210000004995 male reproductive system Anatomy 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 229960001855 mannitol Drugs 0.000 description 2
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 235000012149 noodles Nutrition 0.000 description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 239000012188 paraffin wax Substances 0.000 description 2
- 239000006072 paste Substances 0.000 description 2
- 239000000312 peanut oil Substances 0.000 description 2
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- VYMDGNCVAMGZFE-UHFFFAOYSA-N phenylbutazonum Chemical compound O=C1C(CCCC)C(=O)N(C=2C=CC=CC=2)N1C1=CC=CC=C1 VYMDGNCVAMGZFE-UHFFFAOYSA-N 0.000 description 2
- 239000011505 plaster Substances 0.000 description 2
- 229920002401 polyacrylamide Polymers 0.000 description 2
- 239000011148 porous material Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 210000000064 prostate epithelial cell Anatomy 0.000 description 2
- 239000012268 protein inhibitor Substances 0.000 description 2
- 229940121649 protein inhibitor Drugs 0.000 description 2
- 238000010814 radioimmunoprecipitation assay Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 2
- 235000012239 silicon dioxide Nutrition 0.000 description 2
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 description 2
- 229960004025 sodium salicylate Drugs 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- GGCZERPQGJTIQP-UHFFFAOYSA-N sodium;9,10-dioxoanthracene-2-sulfonic acid Chemical compound [Na+].C1=CC=C2C(=O)C3=CC(S(=O)(=O)O)=CC=C3C(=O)C2=C1 GGCZERPQGJTIQP-UHFFFAOYSA-N 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 239000007921 spray Substances 0.000 description 2
- 239000008117 stearic acid Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 238000013268 sustained release Methods 0.000 description 2
- 239000012730 sustained-release form Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 239000002562 thickening agent Substances 0.000 description 2
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
- 238000004704 ultra performance liquid chromatography Methods 0.000 description 2
- 229940088594 vitamin Drugs 0.000 description 2
- 235000013343 vitamin Nutrition 0.000 description 2
- 239000011782 vitamin Substances 0.000 description 2
- 229930003231 vitamin Natural products 0.000 description 2
- 239000003643 water by type Substances 0.000 description 2
- 239000001993 wax Substances 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- 235000010447 xylitol Nutrition 0.000 description 2
- 239000000811 xylitol Substances 0.000 description 2
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 2
- 229960002675 xylitol Drugs 0.000 description 2
- CWKVFRNCODQPDB-UHFFFAOYSA-N 1-(2-aminoethylamino)propan-2-ol Chemical compound CC(O)CNCCN CWKVFRNCODQPDB-UHFFFAOYSA-N 0.000 description 1
- QIZPVNNYFKFJAD-UHFFFAOYSA-N 1-chloro-2-prop-1-ynylbenzene Chemical compound CC#CC1=CC=CC=C1Cl QIZPVNNYFKFJAD-UHFFFAOYSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- FKOKUHFZNIUSLW-UHFFFAOYSA-N 2-Hydroxypropyl stearate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(C)O FKOKUHFZNIUSLW-UHFFFAOYSA-N 0.000 description 1
- SXAMGRAIZSSWIH-UHFFFAOYSA-N 2-[3-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-1,2,4-oxadiazol-5-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C1=NOC(=N1)CC(=O)N1CC2=C(CC1)NN=N2 SXAMGRAIZSSWIH-UHFFFAOYSA-N 0.000 description 1
- JQMFQLVAJGZSQS-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]-N-(2-oxo-3H-1,3-benzoxazol-6-yl)acetamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)CC(=O)NC1=CC2=C(NC(O2)=O)C=C1 JQMFQLVAJGZSQS-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 description 1
- 229940113178 5 Alpha reductase inhibitor Drugs 0.000 description 1
- QGXBDMJGAMFCBF-HLUDHZFRSA-N 5α-Androsterone Chemical compound C1[C@H](O)CC[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CC[C@H]21 QGXBDMJGAMFCBF-HLUDHZFRSA-N 0.000 description 1
- CONKBQPVFMXDOV-QHCPKHFHSA-N 6-[(5S)-5-[[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]methyl]-2-oxo-1,3-oxazolidin-3-yl]-3H-1,3-benzoxazol-2-one Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)C[C@H]1CN(C(O1)=O)C1=CC2=C(NC(O2)=O)C=C1 CONKBQPVFMXDOV-QHCPKHFHSA-N 0.000 description 1
- 241000007128 Abelia Species 0.000 description 1
- 208000002874 Acne Vulgaris Diseases 0.000 description 1
- 208000034014 Adult-onset autosomal dominant leukodystrophy Diseases 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
- 239000005695 Ammonium acetate Substances 0.000 description 1
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 229920000856 Amylose Polymers 0.000 description 1
- 108010011485 Aspartame Proteins 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
- 229920000623 Cellulose acetate phthalate Polymers 0.000 description 1
- PTHCMJGKKRQCBF-UHFFFAOYSA-N Cellulose, microcrystalline Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC)C(CO)O1 PTHCMJGKKRQCBF-UHFFFAOYSA-N 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
- 238000000116 DAPI staining Methods 0.000 description 1
- FMGSKLZLMKYGDP-UHFFFAOYSA-N Dehydroepiandrosterone Natural products C1C(O)CCC2(C)C3CCC(C)(C(CC4)=O)C4C3CC=C21 FMGSKLZLMKYGDP-UHFFFAOYSA-N 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 239000003109 Disodium ethylene diamine tetraacetate Substances 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 description 1
- 241000283073 Equus caballus Species 0.000 description 1
- 208000010228 Erectile Dysfunction Diseases 0.000 description 1
- QGXBDMJGAMFCBF-UHFFFAOYSA-N Etiocholanolone Natural products C1C(O)CCC2(C)C3CCC(C)(C(CC4)=O)C4C3CCC21 QGXBDMJGAMFCBF-UHFFFAOYSA-N 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 229920002907 Guar gum Polymers 0.000 description 1
- 206010020880 Hypertrophy Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 206010024419 Libido decreased Diseases 0.000 description 1
- 235000019738 Limestone Nutrition 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- MQHWFIOJQSCFNM-UHFFFAOYSA-L Magnesium salicylate Chemical compound [Mg+2].OC1=CC=CC=C1C([O-])=O.OC1=CC=CC=C1C([O-])=O MQHWFIOJQSCFNM-UHFFFAOYSA-L 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 239000004909 Moisturizer Substances 0.000 description 1
- 241001539019 Monolene Species 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 235000019482 Palm oil Nutrition 0.000 description 1
- 239000005662 Paraffin oil Substances 0.000 description 1
- 229920002230 Pectic acid Polymers 0.000 description 1
- 239000001888 Peptone Substances 0.000 description 1
- 108010080698 Peptones Proteins 0.000 description 1
- 241000009328 Perro Species 0.000 description 1
- 108090000430 Phosphatidylinositol 3-kinases Proteins 0.000 description 1
- 206010036018 Pollakiuria Diseases 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 229920003110 Primojel Polymers 0.000 description 1
- HCBIBCJNVBAKAB-UHFFFAOYSA-N Procaine hydrochloride Chemical compound Cl.CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 HCBIBCJNVBAKAB-UHFFFAOYSA-N 0.000 description 1
- 102000005765 Proto-Oncogene Proteins c-akt Human genes 0.000 description 1
- 241000750718 Pterocarpus santalinus Species 0.000 description 1
- 229920001218 Pullulan Polymers 0.000 description 1
- 239000004373 Pullulan Substances 0.000 description 1
- 239000012083 RIPA buffer Substances 0.000 description 1
- 206010057190 Respiratory tract infections Diseases 0.000 description 1
- 108091027981 Response element Proteins 0.000 description 1
- 229920001800 Shellac Polymers 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- BCKXLBQYZLBQEK-KVVVOXFISA-M Sodium oleate Chemical compound [Na+].CCCCCCCC\C=C/CCCCCCCC([O-])=O BCKXLBQYZLBQEK-KVVVOXFISA-M 0.000 description 1
- 244000228451 Stevia rebaudiana Species 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 244000299461 Theobroma cacao Species 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 102000046299 Transforming Growth Factor beta1 Human genes 0.000 description 1
- 101800002279 Transforming growth factor beta-1 Proteins 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 206010046306 Upper respiratory tract infection Diseases 0.000 description 1
- DFPAKSUCGFBDDF-ZQBYOMGUSA-N [14c]-nicotinamide Chemical compound N[14C](=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-ZQBYOMGUSA-N 0.000 description 1
- 206010000496 acne Diseases 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 239000003463 adsorbent Substances 0.000 description 1
- 201000001452 adult-onset autosomal dominant demyelinating leukodystrophy Diseases 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 235000013334 alcoholic beverage Nutrition 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 1
- 150000001346 alkyl aryl ethers Chemical class 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- CEGOLXSVJUTHNZ-UHFFFAOYSA-K aluminium tristearate Chemical compound [Al+3].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CEGOLXSVJUTHNZ-UHFFFAOYSA-K 0.000 description 1
- SNAAJJQQZSMGQD-UHFFFAOYSA-N aluminum magnesium Chemical compound [Mg].[Al] SNAAJJQQZSMGQD-UHFFFAOYSA-N 0.000 description 1
- 229940063655 aluminum stearate Drugs 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 235000019257 ammonium acetate Nutrition 0.000 description 1
- 229940043376 ammonium acetate Drugs 0.000 description 1
- 239000001099 ammonium carbonate Substances 0.000 description 1
- 235000012501 ammonium carbonate Nutrition 0.000 description 1
- 239000003263 anabolic agent Substances 0.000 description 1
- 229940070021 anabolic steroids Drugs 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 230000001548 androgenic effect Effects 0.000 description 1
- 229940061641 androsterone Drugs 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 230000002280 anti-androgenic effect Effects 0.000 description 1
- 239000000051 antiandrogen Substances 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000011260 aqueous acid Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 239000000605 aspartame Substances 0.000 description 1
- 235000010357 aspartame Nutrition 0.000 description 1
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 1
- 229960003438 aspartame Drugs 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 239000000440 bentonite Substances 0.000 description 1
- 229910000278 bentonite Inorganic materials 0.000 description 1
- 235000012216 bentonite Nutrition 0.000 description 1
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 235000008429 bread Nutrition 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- FNAQSUUGMSOBHW-UHFFFAOYSA-H calcium citrate Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O FNAQSUUGMSOBHW-UHFFFAOYSA-H 0.000 description 1
- 239000001354 calcium citrate Substances 0.000 description 1
- 239000004227 calcium gluconate Substances 0.000 description 1
- 235000013927 calcium gluconate Nutrition 0.000 description 1
- 229960004494 calcium gluconate Drugs 0.000 description 1
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
- MKJXYGKVIBWPFZ-UHFFFAOYSA-L calcium lactate Chemical compound [Ca+2].CC(O)C([O-])=O.CC(O)C([O-])=O MKJXYGKVIBWPFZ-UHFFFAOYSA-L 0.000 description 1
- 239000001527 calcium lactate Substances 0.000 description 1
- 235000011086 calcium lactate Nutrition 0.000 description 1
- 229960002401 calcium lactate Drugs 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 239000000378 calcium silicate Substances 0.000 description 1
- 229910052918 calcium silicate Inorganic materials 0.000 description 1
- 235000012241 calcium silicate Nutrition 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 235000011132 calcium sulphate Nutrition 0.000 description 1
- NEEHYRZPVYRGPP-UHFFFAOYSA-L calcium;2,3,4,5,6-pentahydroxyhexanoate Chemical compound [Ca+2].OCC(O)C(O)C(O)C(O)C([O-])=O.OCC(O)C(O)C(O)C(O)C([O-])=O NEEHYRZPVYRGPP-UHFFFAOYSA-L 0.000 description 1
- OYACROKNLOSFPA-UHFFFAOYSA-N calcium;dioxido(oxo)silane Chemical compound [Ca+2].[O-][Si]([O-])=O OYACROKNLOSFPA-UHFFFAOYSA-N 0.000 description 1
- 235000013877 carbamide Nutrition 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 235000014171 carbonated beverage Nutrition 0.000 description 1
- 238000010000 carbonizing Methods 0.000 description 1
- 229940084030 carboxymethylcellulose calcium Drugs 0.000 description 1
- 238000012754 cardiac puncture Methods 0.000 description 1
- 230000022131 cell cycle Effects 0.000 description 1
- 229940081734 cellulose acetate phthalate Drugs 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 235000015218 chewing gum Nutrition 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- 235000019219 chocolate Nutrition 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 239000007979 citrate buffer Substances 0.000 description 1
- 239000008119 colloidal silica Substances 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 235000008504 concentrate Nutrition 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- 235000013365 dairy product Nutrition 0.000 description 1
- FMGSKLZLMKYGDP-USOAJAOKSA-N dehydroepiandrosterone Chemical compound C1[C@@H](O)CC[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CC=C21 FMGSKLZLMKYGDP-USOAJAOKSA-N 0.000 description 1
- 235000011850 desserts Nutrition 0.000 description 1
- 235000019700 dicalcium phosphate Nutrition 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- UGMCXQCYOVCMTB-UHFFFAOYSA-K dihydroxy(stearato)aluminium Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[Al](O)O UGMCXQCYOVCMTB-UHFFFAOYSA-K 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- AIUDWMLXCFRVDR-UHFFFAOYSA-N dimethyl 2-(3-ethyl-3-methylpentyl)propanedioate Chemical class CCC(C)(CC)CCC(C(=O)OC)C(=O)OC AIUDWMLXCFRVDR-UHFFFAOYSA-N 0.000 description 1
- 238000007598 dipping method Methods 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- 235000019301 disodium ethylene diamine tetraacetate Nutrition 0.000 description 1
- 208000002173 dizziness Diseases 0.000 description 1
- 230000002222 downregulating effect Effects 0.000 description 1
- JWJOTENAMICLJG-QWBYCMEYSA-N dutasteride Chemical compound O=C([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)N[C@@H]4CC3)C)CC[C@@]21C)NC1=CC(C(F)(F)F)=CC=C1C(F)(F)F JWJOTENAMICLJG-QWBYCMEYSA-N 0.000 description 1
- 229960004199 dutasteride Drugs 0.000 description 1
- 230000002500 effect on skin Effects 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 1
- 210000002615 epidermis Anatomy 0.000 description 1
- 210000000918 epididymis Anatomy 0.000 description 1
- 201000010063 epididymitis Diseases 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 230000001815 facial effect Effects 0.000 description 1
- 238000009313 farming Methods 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
- 239000000706 filtrate Substances 0.000 description 1
- 238000000799 fluorescence microscopy Methods 0.000 description 1
- 235000013373 food additive Nutrition 0.000 description 1
- 239000002778 food additive Substances 0.000 description 1
- 235000012041 food component Nutrition 0.000 description 1
- 239000005417 food ingredient Substances 0.000 description 1
- 210000001061 forehead Anatomy 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 238000003304 gavage Methods 0.000 description 1
- 239000000174 gluconic acid Substances 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- YQEMORVAKMFKLG-UHFFFAOYSA-N glycerine monostearate Natural products CCCCCCCCCCCCCCCCCC(=O)OC(CO)CO YQEMORVAKMFKLG-UHFFFAOYSA-N 0.000 description 1
- SVUQHVRAGMNPLW-UHFFFAOYSA-N glycerol monostearate Natural products CCCCCCCCCCCCCCCCC(=O)OCC(O)CO SVUQHVRAGMNPLW-UHFFFAOYSA-N 0.000 description 1
- 235000010417 guar gum Nutrition 0.000 description 1
- 239000000665 guar gum Substances 0.000 description 1
- 229960002154 guar gum Drugs 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 238000007490 hematoxylin and eosin (H&E) staining Methods 0.000 description 1
- 239000004312 hexamethylene tetramine Substances 0.000 description 1
- 235000010299 hexamethylene tetramine Nutrition 0.000 description 1
- VKYKSIONXSXAKP-UHFFFAOYSA-N hexamethylenetetramine Chemical compound C1N(C2)CN3CN1CN2C3 VKYKSIONXSXAKP-UHFFFAOYSA-N 0.000 description 1
- 230000001744 histochemical effect Effects 0.000 description 1
- 239000008173 hydrogenated soybean oil Substances 0.000 description 1
- 239000008172 hydrogenated vegetable oil Substances 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 229920003063 hydroxymethyl cellulose Polymers 0.000 description 1
- 229940031574 hydroxymethyl cellulose Drugs 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 235000015243 ice cream Nutrition 0.000 description 1
- 238000003119 immunoblot Methods 0.000 description 1
- 238000010166 immunofluorescence Methods 0.000 description 1
- 238000003364 immunohistochemistry Methods 0.000 description 1
- 201000001881 impotence Diseases 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 210000002570 interstitial cell Anatomy 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 230000000366 juvenile effect Effects 0.000 description 1
- 229960000829 kaolin Drugs 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 235000015122 lemonade Nutrition 0.000 description 1
- 239000006028 limestone Substances 0.000 description 1
- 229940040145 liniment Drugs 0.000 description 1
- 239000000865 liniment Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 239000000395 magnesium oxide Substances 0.000 description 1
- CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 1
- 229940072082 magnesium salicylate Drugs 0.000 description 1
- AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 235000010449 maltitol Nutrition 0.000 description 1
- 239000000845 maltitol Substances 0.000 description 1
- VQHSOMBJVWLPSR-WUJBLJFYSA-N maltitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-WUJBLJFYSA-N 0.000 description 1
- 229940035436 maltitol Drugs 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 235000013372 meat Nutrition 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 230000006371 metabolic abnormality Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- ZGEGCLOFRBLKSE-UHFFFAOYSA-N methylene hexane Natural products CCCCCC=C ZGEGCLOFRBLKSE-UHFFFAOYSA-N 0.000 description 1
- WPHGSKGZRAQSGP-UHFFFAOYSA-N methylenecyclohexane Natural products C1CCCC2CC21 WPHGSKGZRAQSGP-UHFFFAOYSA-N 0.000 description 1
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 230000001333 moisturizer Effects 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical compound C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 description 1
- 229940097496 nasal spray Drugs 0.000 description 1
- 239000007922 nasal spray Substances 0.000 description 1
- 235000021096 natural sweeteners Nutrition 0.000 description 1
- 230000035407 negative regulation of cell proliferation Effects 0.000 description 1
- 230000017066 negative regulation of growth Effects 0.000 description 1
- 230000011224 negative regulation of urine volume Effects 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 206010029446 nocturia Diseases 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 229920001542 oligosaccharide Polymers 0.000 description 1
- 150000002482 oligosaccharides Chemical class 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000002997 ophthalmic solution Substances 0.000 description 1
- 229940054534 ophthalmic solution Drugs 0.000 description 1
- 229940041678 oral spray Drugs 0.000 description 1
- 239000000668 oral spray Substances 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 239000002540 palm oil Substances 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000007310 pathophysiology Effects 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 235000019319 peptone Nutrition 0.000 description 1
- 229940066779 peptones Drugs 0.000 description 1
- DDBREPKUVSBGFI-UHFFFAOYSA-N phenobarbital Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NC(=O)NC1=O DDBREPKUVSBGFI-UHFFFAOYSA-N 0.000 description 1
- 229960002695 phenobarbital Drugs 0.000 description 1
- FCJSHPDYVMKCHI-UHFFFAOYSA-N phenyl benzoate Chemical compound C=1C=CC=CC=1C(=O)OC1=CC=CC=C1 FCJSHPDYVMKCHI-UHFFFAOYSA-N 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- 229960002895 phenylbutazone Drugs 0.000 description 1
- 229940023488 pill Drugs 0.000 description 1
- 235000013550 pizza Nutrition 0.000 description 1
- 229940068917 polyethylene glycols Drugs 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 150000004804 polysaccharides Chemical class 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229920002689 polyvinyl acetate Polymers 0.000 description 1
- 239000011118 polyvinyl acetate Substances 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 229960002847 prasterone Drugs 0.000 description 1
- 229940088417 precipitated calcium carbonate Drugs 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 229960001309 procaine hydrochloride Drugs 0.000 description 1
- 108060006613 prolamin Proteins 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 229940093625 propylene glycol monostearate Drugs 0.000 description 1
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 230000037209 prostate health Effects 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 235000019423 pullulan Nutrition 0.000 description 1
- 238000010298 pulverizing process Methods 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- HELXLJCILKEWJH-NCGAPWICSA-N rebaudioside A Chemical compound O([C@H]1[C@H](O)[C@@H](CO)O[C@H]([C@@H]1O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O HELXLJCILKEWJH-NCGAPWICSA-N 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000001850 reproductive effect Effects 0.000 description 1
- 208000020029 respiratory tract infectious disease Diseases 0.000 description 1
- XWGJFPHUCFXLBL-UHFFFAOYSA-M rongalite Chemical compound [Na+].OCS([O-])=O XWGJFPHUCFXLBL-UHFFFAOYSA-M 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 235000013580 sausages Nutrition 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 210000001732 sebaceous gland Anatomy 0.000 description 1
- 210000002374 sebum Anatomy 0.000 description 1
- 230000035807 sensation Effects 0.000 description 1
- 235000019615 sensations Nutrition 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 229920002545 silicone oil Polymers 0.000 description 1
- 229910001961 silver nitrate Inorganic materials 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 235000011888 snacks Nutrition 0.000 description 1
- 235000015424 sodium Nutrition 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 229940080237 sodium caseinate Drugs 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
- 239000004289 sodium hydrogen sulphite Substances 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- HYHCSLBZRBJJCH-UHFFFAOYSA-M sodium hydrosulfide Chemical compound [Na+].[SH-] HYHCSLBZRBJJCH-UHFFFAOYSA-M 0.000 description 1
- 229940001584 sodium metabisulfite Drugs 0.000 description 1
- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
- RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 1
- 235000019830 sodium polyphosphate Nutrition 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 229940080350 sodium stearate Drugs 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- YNJORDSKPXMABC-UHFFFAOYSA-M sodium;2-hydroxypropane-2-sulfonate Chemical compound [Na+].CC(C)(O)S([O-])(=O)=O YNJORDSKPXMABC-UHFFFAOYSA-M 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 235000014347 soups Nutrition 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 239000008227 sterile water for injection Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 210000000434 stratum corneum Anatomy 0.000 description 1
- 239000006190 sub-lingual tablet Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 229940098466 sublingual tablet Drugs 0.000 description 1
- 229940035023 sucrose monostearate Drugs 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000007939 sustained release tablet Substances 0.000 description 1
- 210000000106 sweat gland Anatomy 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 235000013616 tea Nutrition 0.000 description 1
- 239000000892 thaumatin Substances 0.000 description 1
- 235000010436 thaumatin Nutrition 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- 229940098465 tincture Drugs 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 229940099456 transforming growth factor beta 1 Drugs 0.000 description 1
- 235000013337 tricalcium citrate Nutrition 0.000 description 1
- 210000001635 urinary tract Anatomy 0.000 description 1
- 229940099259 vaseline Drugs 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 229940100445 wheat starch Drugs 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- XOOUIPVCVHRTMJ-UHFFFAOYSA-L zinc stearate Chemical compound [Zn+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O XOOUIPVCVHRTMJ-UHFFFAOYSA-L 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
-
- 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)
- A61K36/63—Oleaceae (Olive family), e.g. jasmine, lilac or ash tree
-
- 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)
- A61K36/63—Oleaceae (Olive family), e.g. jasmine, lilac or ash tree
- A61K36/634—Forsythia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/60—Sugars; Derivatives thereof
- A61K8/602—Glycosides, e.g. rutin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
- A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
- A61K8/9783—Angiosperms [Magnoliophyta]
- A61K8/9789—Magnoliopsida [dicotyledons]
-
- 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
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q7/00—Preparations for affecting hair growth
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/37—Extraction at elevated pressure or temperature, e.g. pressurized solvent extraction [PSE], supercritical carbon dioxide extraction or subcritical water extraction
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Botany (AREA)
- Mycology (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Alternative & Traditional Medicine (AREA)
- Urology & Nephrology (AREA)
- Medical Informatics (AREA)
- Birds (AREA)
- Molecular Biology (AREA)
- Dermatology (AREA)
- Medicines Containing Plant Substances (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明涉及一种用于治疗雄激素受体相关疾病的药物组合物,其包含翅果连翘提取物作为活性成分。根据本发明的翅果连翘提取物或异槲皮素具有对雄激素受体的抑制活性和对良性前列腺疾病增生动物模型的优异的治疗作用,因此在工业上对于针对雄激素受体相关疾病如良性前列腺增生、雄激素依赖性脱发、排尿困难和前列腺癌的相关治疗药物具有广泛应用。
Description
技术领域
本发明涉及一种用于治疗雄激素受体相关疾病的药物组合物,其包含翅果连翘提取物(Abeliophyllum distichum)作为活性成分。
本申请要求2020年8月31日提交的韩国专利申请第10-2020-0109845号和2021年8月27日提交的韩国专利申请第10-2021-0114027号的优先权和权益,其公开内容通过引用整体并入本文。
背景技术
雄激素是影响男性生殖系统的生长和发育的激素的总称,也指所有表现出雄性激素作用的物质。雄激素是作用于男性第二性征发育的激素,主要由男性睾丸分泌,并且一些也由肾上腺皮质和女性卵巢分泌。雄激素是19碳类固醇,包括细胞内通过还原产生的二氢睾酮,由其转化并分泌到尿液中的雄酮或脱氢表雄酮,由肾上腺皮质分泌的肾上腺雄酮,以及由睾丸分泌的睾酮。
它们控制生殖器官和其它性征的发育、维持和功能。特别地,它们参与骨组织中蛋白质的增加、肾脏重量和尺寸的增加、汗腺和皮脂腺活性的增加以及红细胞的产生。当它们被施用于皮肤时,由于表皮的角质层增厚导致皮脂增加,并且它们也是青少年痤疮发生的原因。此外,雄激素与体毛有关,随着雄激素的增加,男性的面部毛发往往会增加。然而,雄激素也会促进脱发,即前额或头顶的头发脱落。
因此,在由雄激素异常增加引起的雄激素依赖性疾病中,良性前列腺增生(BPH)在过去被定义为由于前列腺增大导致来自下膀胱的尿液的通道阻塞而堵塞尿道,从而导致尿液流量减少的病症,并且在组织学上也被定义为前列腺间质细胞或前列腺的上皮组织细胞增生。然而,由于该疾病的病理生理学过于复杂,无法用这样的定义或概念来解释,目前,在50岁或以上的男性中,BPH被定义为主诉下尿路症状,分为储尿症状,包括尿频(每天排尿8次或更多)、夜尿、尿急(其中有强烈和突然的排尿冲动(需要排尿的感觉)和无法抗拒冲动),以及表明膀胱排空问题的症状,包括排尿犹豫(排尿开始延迟)、间歇性(不连续)和用力排空膀胱。
作为主要临床特征,有前列腺增大和下尿路症状。已知前列腺增大在雄激素存在下发生,并且合成代谢类固醇增加前列腺能力并减少尿液流量,导致尿频增加。
前列腺是雄激素依赖性器官,其中睾酮及其睾丸外来源被激活为更有效的二氢睾酮(DHT)。通常,前列腺是DHT形成的关键器官,并且前列腺内分泌活动的全身作用主要涉及DHT形成及其排泄循环。DHT的产生随着年龄的增长而增加,并导致前列腺生长和肥大增加。其中将5α-还原酶抑制剂施用于BPH男性患者的临床研究确认了DHT的重要性。在许多情况下,已知使用5α-还原酶抑制剂的治疗方法显著降低前列腺的DHT水平和前列腺尺寸。非那雄胺被广泛用于治疗雄激素依赖性疾病,例如男性型脱发、BPH和前列腺癌。非那雄胺是一种竞争性、特异性的5α-还原酶抑制剂,可阻断前列腺、毛囊和其它雄激素敏感组织中睾酮向DHT的转化,从而抑制血清和前列腺中的DHT浓度。常规使用的药物例如非那雄胺和度他雄胺被证明对BPH有治疗作用,但由于诸如勃起功能障碍、性欲减退、头晕和上呼吸道感染的副作用,它们的使用受到严格限制。
同时,韩国尾扇树(Korean Abelia)(学名:翅果连翘)是木犀科的一种树,并且是属于翅果连翘属的唯一物种。它是朝鲜半岛特有植物,稀疏地生长在京畿道和忠清道向阳的山脚下。
然而,目前还没有关于包含翅果连翘提取物作为活性成分的用于预防、减轻或治疗雄激素受体相关疾病的组合物的报道。
发明内容
[技术问题]
因此,本发明人确认了翅果连翘提取物及其活性成分异槲皮素具有抗雄激素活性,抑制雄激素信号传导及相关因子,并且对BPH动物模型有显著效果。从而,完成了本发明。
因此,本发明旨在提供一种用于预防或治疗雄激素受体相关疾病的药物组合物,其包含异槲皮素或翅果连翘提取物作为活性成分。
本发明旨在提供一种用于预防或减轻雄激素受体相关疾病的食品组合物,其包含异槲皮素或翅果连翘提取物作为活性成分。
然而,本发明要解决的技术问题不限于上述问题,本领域的普通技术人员将从以下描述中充分理解本文未描述的其它问题。
[技术方案]
为实现本发明的目的,本发明提供了一种用于预防或治疗雄激素受体相关疾病的药物组合物,其包含异槲皮素或翅果连翘提取物作为活性成分。
本发明还提供了一种用于预防或减轻雄激素受体相关疾病的食品组合物,其包含异槲皮素或翅果连翘提取物作为活性成分。
在本发明的一个实施方案中,提取物可以是使用选自由水、C1至C6醇、丙酮、乙醚、苯、氯仿、乙酸乙酯、二氯甲烷、己烷、环己烷、石油醚、亚临界流体和超临界流体组成的组中的一种或多种溶剂制备的提取物,但本发明不限于此。
在本发明的另一个实施方案中,雄激素受体相关疾病可以是选自由前列腺癌、BPH、排尿困难和脱发组成的组中的一种或多种,但本发明不限于此。
在本发明的又一个实施方案中,翅果连翘提取物可以包含异槲皮素,但本发明不限于此。
在本发明的又一个实施方案中,翅果连翘提取物可以是翅果连翘叶提取物,但本发明不限于此。
在本发明的又一个实施方案中,组合物可以抑制雄激素受体的表达,但本发明不限于此。
在本发明的又一个实施方案中,组合物可以抑制选自由5α-还原酶2(5AR2)、类固醇受体共激活因子1(SRC1)、雌激素受体(ER)和前列腺特异性抗原(PSA)组成的组中的一种或多种雄激素信号传导相关因子,但本发明不限于此。
在本发明的又一个实施方案中,组合物可以抑制PI3K/AKT信号传导通路,但本发明不限于此。
在本发明的又一个实施方案中,食品组合物可以为健康功能食品,但本发明不限于此。
此外,本发明提供了一种预防或治疗雄激素受体相关疾病的方法,其包括将包含异槲皮素或翅果连翘提取物作为活性成分的组合物施用于受试者。
此外,本发明还提供了包含异槲皮素或翅果连翘提取物作为活性成分的组合物用于预防或治疗雄激素受体相关疾病的用途。
此外,本发明还提供了异槲皮素或翅果连翘提取物用于生产预防或治疗雄激素受体相关疾病的药物的用途。
[有益效果]
由于根据本发明的翅果连翘提取物或异槲皮素具有雄激素受体抑制活性,并且对良性前列腺增生(BPH)动物模型具有优异的治疗作用,其可广泛应用于与雄激素受体相关疾病有关的行业,包括BPH、雄激素依赖性脱发、排尿困难和前列腺癌。
附图说明
图1a和1b显示了通过用翅果连翘叶(ADL)热水(D.W.)提取物、ADL乙醇(EtOH)提取物和ADL己烷提取物处理前列腺细胞(LNCaP)对睾酮(TP)诱导的AR、5AR2和PSA过表达的抑制作用。
图2了显示通过荧光染色确认的通过用ADL热水(ADLD)提取物、ADL乙醇(ADLE)提取物和ADL己烷(ADLH)提取物处理前列腺细胞(LNCaP)对睾酮(TP)诱导的AR、5AR2和PSA过表达的抑制作用,通过荧光染色确认。
图3显示了根据收获ADL的时间对睾酮(TP)诱导的AR、5AR2和PSA过表达的抑制作用。
图4显示了用于分析ADLE提取物的代谢物的色谱图。
图5a和5b显示了四种翅果连翘功能成分(异槲皮素(IQ)、芦丁、绿原酸(CA)和异鼠李素3-葡萄糖苷-7-鼠李糖苷(IR))对睾酮(TP)诱导的AR、5AR2和PSA过表达的抑制作用。
图6a和6b显示了异槲皮素(IQ)的浓度对睾酮(TP)诱导的AR、5AR2、PSA和PI3K过表达的抑制作用(阳性对照:Fi,非那雄胺)。
图7a和7b显示了根据异槲皮素(IQ)和ADL提取物的浓度对睾酮(TP)诱导的PI3K(Cell Signaling)、PCNA(SantaCruz)和细胞周期蛋白D1(Cell Signaling)的抑制作用。
图8显示了分析根据提取翅果连翘的时间异槲皮素含量的结果。
图9显示了良性前列腺增生(BPH)动物模型的制作过程,以及翅果连翘提取物的施用方案(阳性对照:锯棕榈(saw)或非那雄胺(Fi))。
图10a至10e显示了在向BPH动物模型口服施用100mg/kg/d的翅果连翘提取物后测量前列腺指数的结果,其中图10a显示了前列腺尺寸,图10b显示了前列腺重量,图10c显示了前列腺重量相对于体重的比率,图10d显示了前列腺组织的管腔区域,并且图10e显示了前列腺组织的上皮厚度。
图11a显示了在向BPH动物模型口服施用100mg/kg/d的翅果连翘提取物后获得的前列腺组织中5AR2、SCR1、AR、ER和PSA的表达水平。
图11b显示了在向BPH动物模型口服施用100mg/kg/d的翅果连翘提取物后分析前列腺组织中5AR2、SCR1、AR、ER和PSA表达水平的定量结果。
图11c显示了在向BPH动物模型口服施用100mg/kg/d的翅果连翘提取物后获得的用于观察前列腺组织中前列腺上皮细胞的H&E染色的结果。
图11d显示了在向BPH动物模型口服施用100mg/kg/d的翅果连翘提取物后获得的测量血清中的DHT水平的结果。
图12a显示了在向BPH动物模型口服施用100mg/kg/d的翅果连翘提取物后获得的测量前列腺组织中PI3K、p-AKT和t-AKT的表达水平的结果。
图12b显示了在向BPH动物模型口服施用100mg/kg/d的翅果连翘提取物后获得的分析前列腺组织中PI3K、p-AKT和t-AKT的表达水平的定量结果。
图13a显示了在向BPH动物模型口服施用100mg/kg/d的翅果连翘提取物后获得的测量前列腺组织中EGF(SantaCruz)、IGF-1(ABCam)、TGF-1β(SantaCruz)和VEGF(SantaCruz)的表达水平的结果。
图13b显示了在向BPH动物模型口服施用100mg/kg/d的翅果连翘提取物后获得的分析前列腺组织中EGF(SantaCruz)、IGF-1(ABCam)、TGF-1β(SantaCruz)和VEGF(SantaCruz)的表达水平的定量结果。
图14a显示了在向BPH动物模型口服施用100mg/kg/d的翅果连翘提取物后获得的测量前列腺组织中PCNA和细胞周期蛋白D1的表达水平的结果。
图14b显示了在向BPH动物模型口服施用100mg/kg/d的翅果连翘提取物后获得的分析前列腺组织中PCNA和细胞周期蛋白D1的表达水平的定量结果。
图14c显示了在向BPH动物模型口服施用100mg/kg/d的翅果连翘提取物后获得的用于观察前列腺组织中PCNA的组织化学染色结果。
图15a显示了在向BPH动物模型口服施用100mg/kg/d的翅果连翘提取物后获得的测量前列腺组织中Bax(SantaCruz)和Bcl-2(Cell Signaling)的表达水平的结果。
图15b显示了在向BPH动物模型口服施用100mg/kg/d的翅果连翘提取物后获得的分析前列腺组织中Bax(SantaCruz)和Bcl-2(Cell Signaling)的表达水平的定量结果。
图16显示了在向BPH动物模型口服施用1mg/kg或10mg/kg的异槲皮素(IQ)后测量前列腺指数的结果(A:前列腺尺寸,B:前列腺重量,C:前列腺重量与体重的比率)。
图17显示了在向BPH动物模型口服施用1mg/kg或10mg/kg的异槲皮素(IQ)后获得的对前列腺组织中AR、SRC-1、5AR2表达的抑制作用。
具体实施方式
本发明提供了一种用于预防或治疗雄激素受体相关疾病的药物组合物,其包含异槲皮素或翅果连翘提取物作为活性成分。
以下,对本发明进行详细说明。
本文中使用的名称“翅果连翘(Abeliophyllum distichum)”更优选为Abeliophyllum distichum Nakai,但本发明不限于此。翅果连翘是属于木犀科的树,并且是属于翅果连翘属的唯一物种。它是朝鲜半岛特有植物,稀疏地生长在京畿道和忠清道向阳的山脚下。
在本发明中,翅果连翘可以在不破坏其原貌的情况下使用,或者可以在考虑到本领域普通技术人员期望的处理速度和处理(制造)效率的预处理过程之后使用,并且预处理过程可包括,例如,通常的筛选、用水洗涤、切割、磨粉和干燥。
在本发明中,翅果连翘的收获期没有限制,但可以在春季或秋季,优选在秋季,更优选在深秋收获。
本文中使用的翅果连翘提取物可以从整个植物体或植物的一部分获得,例如选自由茎、根、叶、果实和花组成的组中的一种或多种。在本发明的一个实施方案中,翅果连翘提取物获自其叶。
本发明的翅果连翘提取物可以通过提取天然材料的已知方法提取。例如,可以用选自由水、C1至C6有机溶剂和亚临界或超临界流体组成的组中的一种或多种来提取本发明的翅果连翘提取物。C1至C6有机溶剂可以是选自由C1至C6醇、丙酮、醚、苯、氯仿、乙酸乙酯、二氯甲烷、己烷、环己烷和石油醚组成的组中的一种或多种,但本发明不限于此。
本发明的翅果连翘提取物优选用乙醇提取,但本发明不限于此。提取方法使用上述溶剂,可以采用诸如浸渍、消化、加热的常规提取方法。
在本发明中,对乙醇浓度没有限制,例如,本发明的翅果连翘提取物可以是30至100%、40至100%、50至100%、60至100%、50至90%、60至90%、60至80%、65至75%或约70%的乙醇提取物。
在本发明中,异槲皮素按照IUPAC名称也被称为3-(β-D-吡喃葡萄糖氧基)-3',4',5,7-四羟基黄酮,是以C21H20O12表示的化合物,分子量为464.379[g/mol],并在CAS登记号482-35-9下登记。异槲皮素可由下式1表示。
[式1]
本发明的组合物可以抑制雄激素受体的表达,但本发明不限于此。
本发明的组合物可以抑制选自由5α-还原酶2(5AR2)、类固醇受体共激活因子1(SRC1)、雌激素受体(ER)和前列腺特异性抗原(PSA)组成的组中的一种或多种雄激素信号传导相关因子,但本发明不限于此。
本发明的组合物可以抑制PI3K/AKT信号传导通路,但本发明不限于此。
在本发明的一个实施方案中,作为确认根据用于翅果连翘提取物的溶剂的雄激素信号传导相关因子如AR、5AR2和PSA表达水平的结果,确认了翅果连翘乙醇提取物具有最优异的抑制作用(见实施例2)。
在本发明的一个实施方案中,作为确认根据翅果连翘叶的收获期的雄激素信号传导相关因子如AR、5AR2和PSA表达水平的结果,确认了在晚秋收获的翅果连翘的提取物的抑制作用优于在晚春收获的翅果连翘的提取物的抑制作用(参见实施例4)。
在本发明的一个实施方案中,作为确认根据翅果连翘叶提取物的功能成分之一异槲皮素处理的雄激素信号传导相关因子AR、5AR2和PSA表达水平的结果,确认了异槲皮素具有显著的AR、5AR2和PSA抑制作用(参见实施例5-2)。
在本发明的一个实施方案中,作为确认根据异槲皮素处理对PI3K和细胞增殖因子增殖细胞核抗原(PCNA)和细胞周期蛋白D1表达的下调作用的结果,确认了根据异槲皮素和翅果连翘叶乙醇提取物的浓度对PI3K、PCNA和细胞周期蛋白D1的表达显著降低(参见实施例5-3)。
在本发明的一个实施方案中,作为在BPH动物模型中确认翅果连翘提取物和异槲皮素的BPH治疗效果的结果,确认了翅果连翘提取物和异槲皮素显著改善前列腺指数,并显著改善雄激素受体和前列腺相关因子的水平(参见实施例7)。
因此,本发明的翅果连翘提取物或异槲皮素可以用作治疗雄激素受体相关疾病的组合物的活性成分。
本文使用的术语“雄激素受体相关疾病”是指由于雄激素受体(AR)的异常、过度刺激而可能发生的由信号传递引起的各种疾病,并且所述疾病可以包括但不特定局限于前列腺癌、BPH、排尿困难和脱发等。
前列腺的正常发育和保持取决于雄性激素或雄激素通过雄激素受体的作用。在正常前列腺中,每天有1%至2%的细胞死亡并被新细胞替代,这是由雄激素受体调节的正常前列腺功能的一部分。因此,维持雄激素受体的正常功能是前列腺健康的关键。特别地,前列腺癌细胞主要依赖于雄激素受体来生长和存活,并且对于雄激素依赖性前列腺癌和雄激素非依赖性前列腺癌二者都是必需的。因此,抑制雄激素受体转录作用的疗法在前列腺癌的治疗中起重要作用。
此外,BPH发生的最大诱因是影响男性生殖系统的生长发育的雄激素(AH),并且雄激素与雄激素受体(AR)结合,引起前列腺增大。因此,在BPH治疗中,正在进行着眼于雄激素受体表达下调的研究。
同时,雄激素受体与脱发也有重要关系。睾酮遇到5-α-还原酶并转化为二氢睾酮(DHT)。过多形成的DHT与毛囊中的雄激素受体结合,导致脱发。雄激素(AH)仅通过雄激素受体起作用,并且睾酮和二氢睾酮的作用机制取决于与雄激素受体的结合。因此,为了防止脱发,毛囊中雄激素受体表达的下调很重要。
因此,根据本发明的翅果连翘提取物或异槲皮素可以在转录水平(mRNA水平)下调雄激素受体的表达,因此可有效用于治疗雄激素受体相关疾病,如前列腺癌、BPH、排尿困难和脱发等。
在本发明中,异槲皮素可以以药学上可接受的盐的形式作为活性成分包括在内。术语“药学上可接受的盐”包括衍生自药学上可接受的无机酸、有机酸或碱的盐。
合适的酸的实例可以包括盐酸、溴酸、硫酸、硝酸、高氯酸、富马酸、马来酸、磷酸、乙醇酸、乳酸、水杨酸、琥珀酸、甲苯-对-磺酸、酒石酸、乙酸、柠檬酸、甲磺酸、甲酸、苯甲酸、丙二酸、葡萄糖酸、萘-2-磺酸和苯磺酸。酸加成盐可以通过常规方法制备,例如通过将化合物溶解在过量的酸水溶液中并使用水混溶性有机溶剂如甲醇、乙醇、丙酮或乙腈使盐沉淀。此外,酸加成盐可以通过在水中加热等摩尔量的化合物和酸或醇,然后通过蒸发或抽吸过滤沉淀的盐使混合物脱水来制备。
衍生自合适碱的盐可以包括钠和钾等碱金属、镁等碱土金属、和铵,但本发明不限于此。碱金属或碱土金属可以通过例如将化合物溶解在过量的碱金属氢氧化物或碱土金属氢氧化物溶液中、过滤未溶解的化合物盐、然后蒸发并干燥滤液来获得。此处,作为金属盐,特别地制备钠盐、钾盐或钙盐适合于药物用途,并且与之对应的银盐可以通过使碱金属或碱土金属盐与合适的银盐(例如硝酸银)反应而得到。
本发明组合物中翅果连翘提取物或异槲皮素的含量可以根据疾病的症状、症状的进展或患者的状况适当调整,并且可以为基于组合物总重量的例如0.0001至99.9重量%,或0.001至50重量%,但本发明不限于此。含量比是基于去除溶剂后的干燥含量的值。
根据本发明的药物组合物可以还包含通常用于制备药物组合物的合适载体、辅料和稀释剂。辅料可以是例如选自由稀释剂、粘合剂、崩解剂、润滑剂、吸附剂、保湿剂、薄膜包衣材料和控释添加剂中的一种或多种。
根据常规方法,根据本发明的药物组合物可以配制成散剂、颗粒剂、缓释颗粒剂、肠溶颗粒剂、液体剂、眼用溶液剂、酏剂、乳剂、混悬剂、醑剂、锭剂、芳香水、柠檬水、片剂、缓释片剂、肠溶片剂、舌下片剂、硬胶囊剂、软胶囊剂、缓释胶囊剂、肠溶胶囊剂、丸剂、酊剂、软提取物、干提取物、液体提取物、注射剂、胶囊、灌注液、硬膏剂、洗剂、糊剂、喷雾剂、吸入剂、贴剂、无菌注射剂、或气雾剂等的外用制剂,并且外用制剂可以配制成乳膏剂、凝胶剂、贴剂、喷雾剂、软膏剂、硬膏剂、洗剂、搽剂、糊剂或巴布剂。
可以包括在根据本发明的药物组合物中的载体、辅料和稀释剂可以包括乳糖、葡萄糖、蔗糖、低聚糖、山梨糖醇、甘露糖醇、木糖醇、赤藓糖醇、麦芽糖醇、淀粉、阿拉伯树胶、海藻酸盐、明胶、磷酸钙、硅酸钙、纤维素、甲基纤维素、微晶纤维素、聚乙烯吡咯烷酮、水、羟基苯甲酸甲酯、羟基苯甲酸丙酯、滑石粉、硬脂酸镁和矿物油。
药物组合物可以与常用的稀释剂或辅料如填充剂、增稠剂、粘合剂、润湿剂、崩解剂和表面活性剂一起配制。
作为用于片剂、散剂、颗粒剂、胶囊剂、丸剂和锭剂的添加剂,可以使用辅料,例如玉米淀粉、马铃薯淀粉、小麦淀粉、乳糖、蔗糖、葡萄糖、果糖、二甘露糖醇、沉淀碳酸钙、合成硅酸铝、磷酸氢钙、硫酸钙、氯化钠、碳酸氢钠、精制羊毛脂、微晶纤维素、糊精、海藻酸钠、甲基纤维素、羧甲基纤维素、羧甲基纤维素钠、高岭土、尿素、胶体硅胶、羟丙基淀粉、羟丙基甲基纤维素、HPMC 1928、HPMC 2208、HPMC 2906、HPMC2910、丙二醇、酪蛋白、乳酸钙和Primojel;粘合剂,例如明胶、阿拉伯树胶、乙醇、琼脂粉、乙酸邻苯二甲酸纤维素、羧甲基纤维素、羧甲基纤维素钙、葡萄糖、纯净水、酪蛋白酸钠、甘油、硬脂酸、羧甲基纤维素钠、甲基纤维素钠、甲基纤维素、微晶纤维素、糊精、羟基纤维素、羟丙基淀粉、羟甲基纤维素、精制虫胶、淀粉粉、羟丙基纤维素、羟丙基甲基纤维素、聚乙烯醇和聚乙烯吡咯烷酮;崩解剂,例如羟丙基甲基纤维素、玉米淀粉、琼脂粉、甲基纤维素、膨润土、羟丙基淀粉、羧甲基纤维素钠、柠檬酸钙、月桂基硫酸钠、硅酸酐、1-羟丙基纤维素、葡聚糖、离子交换树脂、聚乙酸乙烯酯、甲醛处理的酪蛋白和明胶、海藻酸、直链淀粉、瓜尔胶、碳酸氢钠、聚乙烯吡咯烷酮、磷酸钙、凝胶淀粉、阿拉伯树胶、支链淀粉、果胶、聚磷酸钠、乙基纤维素、蔗糖、硅酸镁铝、二山梨糖醇溶液和轻质无水硅酸;以及润滑剂,例如硬脂酸钙、硬脂酸镁、硬脂酸、氢化植物油、滑石粉、石灰石高岭土、凡士林、硬脂酸钠、可可脂、水杨酸钠、水杨酸镁、聚乙二醇4000和6000、液体石蜡、氢化大豆油(Lubri蜡)、硬脂酸铝、硬脂酸锌、月桂基硫酸钠、氧化镁、聚乙二醇、合成硅酸铝、硅酸酐、高级脂肪酸、高级醇、硅油、石蜡油、聚乙二醇脂肪酸醚、淀粉、氯化钠、乙酸钠、油酸钠、二亮氨酸和轻质无水硅酸。
用于根据本发明的液体剂的添加剂可以是水、稀盐酸、稀硫酸、柠檬酸钠、单硬脂酸酯蔗糖、聚氧乙烯山梨糖醇脂肪酸酯(Tween酯)、聚氧乙烯单烷基醚、羊毛脂醚、羊毛脂酯、乙酸、盐酸、乙酸、盐酸、氨水、碳酸铵、氢氧化钾、氢氧化钠、谷醇溶蛋白、聚乙烯吡咯烷酮、乙基纤维素和羧甲基纤维素钠。
在根据本发明的糖浆剂中,可以使用白糖、其它糖类或甜味剂的溶液,并且如果需要,可以使用调味剂、着色剂、防腐剂、稳定剂、助悬剂、乳化剂或粘度控制剂。
在根据本发明的乳剂中,可以使用蒸馏水,并且如果需要,可以使用乳化剂、防腐剂、稳定剂或调味剂。
在根据本发明的混悬剂中,可以使用助悬剂,例如阿拉伯树胶、黄芪胶、甲基纤维素、羧甲基纤维素、羧甲基纤维素钠、羧甲基纤维素钠、微晶纤维素、海藻酸钠、羟丙基甲基纤维素(HPMC)、HPMC 1828、HPMC 2906或HPMC 2910,并且如果需要,可以使用表面活性剂、防腐剂、稳定剂、着色剂或调味剂。
在根据本发明的注射剂中,可以包括溶剂,例如注射用无菌水、注射用0.9%氯化钠、林格溶液、注射用葡萄糖、注射用葡萄糖+氯化钠、PEG、乳酸林格溶液、乙醇、丙二醇、非挥发油——芝麻油、棉籽油、花生油、大豆油、玉米油、油酸乙酯、肉豆蔻酸异丙酯或苯甲酸苯酯;增溶剂,例如苯甲酸钠、水杨酸钠、乙酸钠、尿素、氨基甲酸酯、单乙基乙胺、苯基丁氮酮(butazolidine)、丙二醇、Tween、烟酰胺、六胺或二甲基乙酰胺;缓冲剂,例如弱酸及其盐(乙酸和乙酸钠)、弱碱及其盐(氨和乙酸铵)、有机化合物、蛋白质、白蛋白、蛋白胨或树胶;等渗剂,例如氯化钠;稳定剂,例如亚硫酸氢钠(NaHSO3)、二氧化碳气体、焦亚硫酸钠(Na2S2O3)、亚硫酸钠(Na2SO3)、氮气(N2)或乙二胺四乙酸;抗氧化剂,例如0.1%氢硫化钠、甲醛次硫酸氢钠、硫脲、乙二胺四乙酸二钠或丙酮亚硫酸氢钠;止痛剂,例如苯甲醇、氯丁醇、盐酸普鲁卡因、葡萄糖或葡萄糖酸钙;或助悬剂,例如CMC钠、海藻酸钠、Tween 80或单硬脂酸铝。
在根据本发明的栓剂中,可以使用基质,例如可可脂、羊毛脂、Witepsol、聚乙二醇、甘油明胶、甲基纤维素、羧甲基纤维素、硬脂酸盐和油酸盐的混合物、Subanal、棉籽油、花生油、棕榈油、可可脂+胆固醇、卵磷脂、Lanette蜡、甘油单硬脂酸酯、Tween或Span、Imhausen、monolene(丙二醇单硬脂酸酯)、甘油、Adeps solidus、Buytyrum Tego-G、CebesPharma 16、hexalide base 95、Cotomar、Hydrokote SP、S-70-XXA、S-70-XX75(S-70-XX95)、Hydrokote 25、Hydrokote 711、Idropostal、Massa estrarium(A、AS、B、C、D、E、I、T)、Mass-MF、Masupol、Masupol-15、neosuppostal-N、paramount-B、supposiro(OSI、OSIX、A、B、C、D、H、L)、栓剂基质IV型(AB、B、A、BC、BBG、E、BGF、C、D、299)、Suppostal(N、Es)、Wecoby(W、R、S、M、Fs)或Tegester甘油三酯基质(TG-95、MA、57)。
用于口服施用的固体制剂可以是片剂、丸剂、散剂、颗粒剂或胶囊剂,并且这样的固体制剂可以通过将至少一种辅料例如淀粉、碳酸钙、蔗糖、乳糖或明胶与活性成分混合来制备。此外,除了简单的辅料外,还可以使用润滑剂如硬脂酸镁和滑石粉。
作为用于口服施用的液体制剂,可以使用混悬剂、内服液、乳剂或糖浆剂,并且可以包括通常使用的简单稀释剂如水或液体石蜡,以及各种类型的辅料,例如润湿剂、甜味剂、香料和防腐剂。用于肠胃外施用的制剂可以是无菌水溶液、非水溶剂、混悬剂、乳剂、冻干剂或栓剂。作为非水溶剂或混悬剂,可以使用丙二醇、聚乙二醇、植物油如橄榄油、或可注射的酯如油酸乙酯。
根据本发明的组合物以药学有效量施用。在本发明中,本文所用的“药学有效量”是指足以在适用于医学治疗的合理利益/风险比下治疗疾病的量,并且有效剂量可以通过包括患者疾病的类型、严重程度、药物活性、对药物的敏感性、施用时间、施用途径和排泄率、治疗持续时间和同时使用的药物在内的参数以及医学领域众所周知的其它参数来确定。
本发明的药物组合物可以单独施用或与其他治疗剂组合施用,并且可以与常规治疗剂顺序施用或同时施用,或在单剂量或多剂量中施用。考虑到所有上述参数,重要的是用最小的剂量达到最大的效果而没有副作用,这样的剂量可以很容易地由本领域的普通技术人员确定。
可以通过多种途径将本发明的药物组合物施用于受试者。可以预期所有施用途径,并且本发明的药物组合物可以通过例如口服施用,皮下注射,腹膜内施用,静脉内、肌肉内或鞘内注射,舌下施用,口腔施用,直肠插入,阴道插入,眼部施用,耳部施用,鼻腔施用,吸入,经口或鼻喷洒、皮肤施用或透皮施用。
本发明的药物组合物可以根据作为活性成分的药物的种类以及包括所治疗的疾病、施用途径、患者的年龄、性别、体重以及疾病的严重程度在内的相关因素来确定。
本文所用的术语“受试者”是指需要治疗的目标,更具体地,哺乳动物例如人或非人灵长类动物、小鼠、大鼠、狗、猫、马或牛,但本发明不限于此。
本文使用的“施用”是指通过任何合适的方法将本发明的组合物提供给受试者。
本文所用术语“预防”是指抑制或延缓靶向疾病发生的所有行为,并且本文所用“治疗”是指通过施用根据本发明的药物组合物而改善或有益地改变靶向疾病或代谢异常的症状所涉及的所有行为,并且本文中使用的“减轻”是指通过施用根据本发明的组合物降低与靶向疾病相关的参数(例如症状的严重程度)的所有行为。
此外,本发明提供一种食品组合物,其包含翅果连翘提取物或异槲皮素作为活性成分。
本文使用的食品的实例包括功能食品和健康功能食品。
当将翅果连翘提取物或异槲皮素用作食品添加剂时,翅果连翘提取物可以单独添加或与其它食品或食品成分组合使用,并且可以根据常规方法适当使用。活性成分的混合量可以根据使用目的(预防、保健或治疗方法)适当确定。通常,当制备食品或饮料时,基于原料,可以以15重量%或更少、或10重量%或更少的量添加本发明的翅果连翘提取物。然而,为了健康和卫生或健康控制而长期食用时,组合物的量可以等于或低于上述范围,并且由于没有安全性方面问题,活性成分可以以大于上述范围的量使用。
对食品的类型没有特别限制。可以向其中添加该材料的食品的实例包括肉、香肠、面包、巧克力、糖果、零食、甜食、披萨、拉面、其它面条、口香糖、乳制品(包括冰淇淋)、各种类型的汤、饮料、茶、饮品、酒精饮料和维生素复合物,以及一般意义上的所有健康功能食品。
根据本发明的健康饮料组合物可以像常规饮料一样包含额外的成分,例如各种调味剂或天然碳水化合物。上述天然碳水化合物为单糖例如葡萄糖和果糖,二糖例如麦芽糖和蔗糖,多糖例如糊精和环糊精,以及糖醇例如木糖醇、山梨糖醇和赤藓糖醇。作为甜味剂,可以使用天然甜味剂例如奇异果甜蛋白和甜叶菊提取物,或合成甜味剂例如糖精和阿斯巴甜。天然碳水化合物的比例通常可以为每100mL本发明的组合物约0.01至0.20g或0.04至0.10g。
此外,本发明的组合物可以包含各种营养素、维生素、电解质、调味剂、果胶酸及其盐、海藻酸及其盐、有机酸、保护性胶体增稠剂、pH调节剂、稳定剂、防腐剂、甘油、酒精或碳酸饮料中使用的碳化剂。除此之外,本发明的组合物可以还包含果肉,用于制造天然果汁、果汁饮料和植物饮料。这些组分可以单独或组合使用。这些添加剂的比例不是很关键,但通常选择在每100重量份本发明的组合物中0.01至0.20重量份的范围内。
[发明方式]
在下文中,为了帮助理解本发明,将提出示例性实施例。然而,提供以下实施例仅是为了使本发明更易于理解,而非限制本发明。
实施例1.实验方法
1-1.热水提取物的制备
翅果连翘由Uri Tree Farming Association提供。将100g翅果连翘(Abeliophyllum distichum Nakai)叶加入锥形瓶中的1000mL蒸馏水(DW)中,并通过在100℃下煮沸提取1小时。将提取物减压过滤(0.2μm孔径)并使用旋转真空浓缩器浓缩。然后将所得浓缩物在冷冻干燥器中冻干5天。
1-2.70%乙醇提取物的制备
将100g翅果连翘叶和1000mL 70%乙醇添加到锥形瓶中,并使用搅拌器提取2小时。然后将从中去除了翅果连翘叶的所得提取物转移到烧杯中。随后,再次向锥形瓶中加入1000mL乙醇,提取2小时,然后转移至烧杯中。后续过程进行三次。随后,使用旋转真空浓缩器浓缩70%乙醇提取物。然后将提取物减压过滤(0.2μm孔径)并在冷冻干燥机中冻干5天。
1-3.95%己烷提取物的制备
将100g翅果连翘叶和1000mL 95%己烷添加到锥形瓶中。后续过程同70%乙醇提取。
1-4.免疫荧光
将载玻片放在12孔板上后,将LNCaP细胞(5x104)接种在载玻片上使其贴壁。24小时后,将细胞用睾酮(100nM)处理,然后用翅果连翘叶(Abeliophyllum distichum Nakai叶,ADL)的热水(D.W.)、乙醇(EtOH)和己烷(Hexane)提取物各100μg/mL处理。24小时后,将细胞固定在冷甲醇中,然后用0.1% Triton X-100处理1小时。用5%山羊血清封闭后,将载玻片用在BSA中稀释的雄激素受体(AR)抗体(1:300)在4℃孵育过夜。然后用AlexaFluor588二抗(1:1000稀释)处理载玻片1小时。使用DAPI染色对细胞核进行染色,然后封固盖玻片。使用Zeiss荧光显微镜确认AR表达水平。
1-5.免疫印迹
将LNCaP细胞用丙酸睾酮(TP)处理以诱导雄激素受体信号传导,用翅果连翘叶热水(D.W.)、乙醇(EtOH)和己烷(Hexane)提取物处理,随后确认抑制雄激素受体(AR,SantaCruz)、5α还原酶(5AR2,ABCam)和前列腺特异性抗原(PSA,SantaCruz)表达的功效,以比较翅果连翘叶提取物对LNCaP细胞中LNCaP细胞的雄激素受体信号传导相关因子的抑制作用。将LNCaP细胞(2x106)接种在6孔板中,并用100nM丙酸睾酮(TP,Tokyo ChemicalIndustry)和翅果连翘叶热水(D.W.)、乙醇(EtOH)和正己烷(Hexane)提取物各100μg/mL处理24小时。此处,将使用1μg/mL雄激素抑制药物非那雄胺(Fi)处理的组用作阳性对照。完成对细胞的处理后,使用蛋白质印迹法分析雄激素受体信号传导抑制作用。首先,将细胞在包含蛋白质抑制剂混合物(Sigma)的放射免疫沉淀测定(RIPA)缓冲液中裂解,并使用BCA测定法估计蛋白质浓度,然后在12% SDS聚丙烯酰胺凝胶中进行电泳。然后使用Mini Trans-转印槽(Bio rad)将凝胶转移到膜上。随后,将膜用一抗在4℃处理12小时。随后,将膜用TBST洗涤3次,每次5分钟,并且用二抗处理1小时。然后使用Azure c300成像系统(AzureBiosystems)通过HPR底物(Advansta Inc.,San Jose,CA,USA)的化学发光检测条带。通过使用ImageJ软件(NIH版本1.48,USA)设置每个样品的面积,然后以与上述相同的方式设置相应的β-肌动蛋白的面积,并通过除以每个样品的β-肌动蛋白的面积来量化条带强度。
1-6.BPH模型的制作和施用计划
将实验动物8周龄雄性SD大鼠(体重200±5g)分为5组,如图9所示,并且在1周适应后,将BPH诱导组通过腹膜内注射苯巴比妥(50mg/kg)麻醉,然后切除睾丸和附睾,然后使用缝合线系住手术部位。所有实验均在无菌环境中进行。在BPH诱导组(BPH)手术恢复后三天,将睾酮溶解在玉米油中,然后每天皮下注射3mg/kg,诱导BPH。对于翅果连翘叶乙醇提取物施用组(BPH+ADLE),将翅果连翘叶乙醇提取物溶解在无菌蒸馏水中并使用灌胃针以100mg/kg口服施用4周。对于作为阳性对照的锯棕榈施用组(BPH+Saw),将锯棕榈溶解在无菌蒸馏水中并以100mg/kg口服施用,对于非那雄胺施用组(BPH+Fi),使用灌胃针以每天1mg/kg口服施用非那雄胺4周。实验结束后,用唑来替尔(zoletil)处死大鼠,通过心脏穿刺收集血液样品,然后分离血清并储存在-80℃。使用无RNA酶手术工具分离前列腺并称重,并储存在-80℃,然后进行蛋白质印迹。
同时,异槲皮素(IQ)施用也以与上述相同的方式并使用相同的对照进行,并且对于低浓度施用组(BPH+IQ1),将IQ溶解在无菌蒸馏水中,然后以1mg/kg口服施用,而对于高浓度施用组(BPH+IQ10),将IQ溶解在无菌蒸馏水中,然后使用灌胃针以10mg/kg口服施用4周。
1-7.苏木精和伊红染色(H&E染色)
将前列腺组织在10%甲醛中固定并脱水,然后包埋在石蜡中。使用切片机(Leica)将石蜡块切成4μm。对于H&E染色,将切下的切片用二甲苯脱石蜡,洗涤,用苏木精染色5分钟,然后用水洗涤5分钟。随后,将所得切片用伊红染色30秒,脱水,然后密封。使用LeicaDM6 Research倒置相位显微镜(Leica,Werzlar,Germany)检查组织。使用LeicaApplication Suite(LAS)显微镜软件测量上皮厚度和管腔面积。
1-8.对雄激素信号传导相关因子表达的抑制作用的分析
对于动物实验组,分析了雄激素信号传导相关因子5α-还原酶2(5AR2)、类固醇受体共激活因子1(SRC1)、雌激素受体(ER)和前列腺特异性抗原(PSA)的蛋白质表达。在切除的前列腺组织中,将腹侧前列腺叶部分用包含蛋白质抑制剂混合物(Sigma)的RIPA缓冲液处理,并使用组织破碎机(tacoPrep Bead beater)将前列腺组织匀浆。之后,使用蛋白质BCA测定估计蛋白质浓度,在12% SDS聚丙烯酰胺凝胶中进行电泳,然后使用Mini Trans-转印槽(Bio rad)将凝胶转移到膜上。然后用针对每种蛋白质的一抗在4℃下对膜处理12小时,用TBST洗涤3次,每次5分钟,然后用二抗处理1小时。随后,然后使用Azure c300成像系统(Azure Biosystems)通过用HPR底物(Advansta Inc.,San Jose,CA,USA)的化学发光检测条带。通过使用ImageJ软件(NIH版本1.48,USA)设置每个样品的面积,然后以与上述相同的方式设置相应的β-肌动蛋白的面积,并通过除以每个样品的β-肌动蛋白的面积来量化条带强度。
1-9.免疫组织化学
将4μm厚的切片脱石蜡并且洗涤,然后将切片浸入0.01M柠檬酸盐缓冲液(pH 6.0)中,并且在微波炉中反应以用于抗原修复。随后,将其在室温下放置10分钟,用D.W.洗涤,并用3% H2O2处理10分钟。将其用山羊血清处理以阻断非特异性结合。然后将切片与抗PCNA和抗AR在4℃下孵育过夜。用二抗处理一小时后,所有免疫染色切片均用苏木精复染,然后使用Leica DM6 Research倒置相位显微镜(Leica,Werzlar,Germany)进行组织分析。
1-10.对PI3K/Akt信号传导通路相关因子表达的抑制作用的分析
确认了雄激素信号传导受到抑制,从而抑制上皮生长因子(EGF)的表达。同时,为了确认PI3K/Akt信号传导通路相关因子磷脂酰肌醇-3-激酶(PI3K)和蛋白激酶B(Akt)的表达是否被翅果连翘叶乙醇提取物抑制,进行了上述蛋白质印迹。
1-11.对生长因子表达的抑制作用的分析
由于雄激素信号传导,生长因子在雄激素反应元件(ARE)中转录,因此它们的表达水平趋于增加。生长因子可能是诱导BPH的主要原因。因此,为了确认翅果连翘叶乙醇提取物施用是否降低了BPH诱导大鼠的前列腺中生长因子的表达,进行了上述蛋白质印迹。确认了生长因子、表皮生长因子(EGF)、胰岛素样生长因子I(IGF-1)、转化生长因子β1(TGF-1β)和血管内皮生长因子(VEGF)的表达水平。
1-12.对前列腺组织中细胞增殖相关因子的抑制作用的分析
为了分析前列腺组织中与细胞增殖相关的代表性因子增殖细胞核抗原(PCNA)和细胞周期蛋白D1蛋白的表达,进行了上述蛋白质印迹。
1-13.使用UPLC-MS分析代谢物
使用Vion UPLCTM系统(Vion,Waters,Milford,MA,USA)对翅果连翘叶乙醇提取物的代谢物进行分析。使用Acquity UPLC BEH C18柱(2.1mm×100mm,1.7μm,Waters)进行LC,柱温设置为55℃。流速设置为0.35mL/min。作为流动相,使用含0.1%甲酸(FA)的水和含0.1%甲酸(FA)的乙腈(ACN)。MS操作条件如下:毛细管电压:2.5kV,样品锥孔电压:20V,离子源温度:200℃,去溶剂化温度:400℃,锥气体流速:30L/h,去溶剂化气体流速:900L/h,扫描时间:0.2秒,扫描范围:m/z 50-1500,碰撞能量斜坡:10-30eV(m/z 50-1000)。
实施例2.根据翅果连翘提取物溶剂的雄激素信号传导相关因子表达的确认
通过用实施例1-1至1-3中制备的翅果连翘叶热水、乙醇和己烷提取物处理前列腺细胞LNCaP细胞来鉴定睾酮诱导的AR、5AR2和PSA的表达水平。已知5AR2在正常前列腺的发育和老年前列腺增大中发挥重要作用,并且AR的表达增加会导致前列腺中DHT与更多AR结合,从而引起前列腺增大。此外,AR与DHT结合,促进前列腺特异性抗原PSA的产生。
如图1a和1a所示,确认了翅果连翘热水提取物显著降低了睾酮增加的AR和5AR2的表达,己烷提取物显著降低了5AR2和PSA的表达,并且乙醇提取物显著抑制所有AR、5AR2和PSA表达,并且与热水提取物和己烷提取物相比,表现出显著优异的抑制作用。
实施例3.根据翅果连翘提取物溶剂的雄激素受体表达的确认
除了实施例2的蛋白质印迹之外,通过荧光染色再次确认了AR抑制作用。
如图2所示,确认了翅果连翘叶乙醇提取物(ADLE)中显示出显著优异的AR抑制作用。
实施例4.根据翅果连翘收获期的雄激素信号传导相关因子表达的确认
确认了根据翅果连翘叶的收获时间对睾酮诱导的AR和PSA之间表达水平的差异。在5月中旬收获晚春收获的叶子,在9月中旬收获深秋收获的叶子,并且按照实施例1-2的乙醇提取方法制备提取物。同时,通过与实施例2相同的方法鉴定雄激素信号传导相关因子。
如图3所示,确认了晚秋收获的翅果连翘叶乙醇提取物中对5AR和PSA表达的抑制作用显著优于晚春收获的翅果连翘叶所获得的。
实施例5.翅果连翘叶乙醇提取物的成分鉴定
5-1.成分分析结果
对于翅果连翘叶乙醇提取物的成分分析,使用UPLC-MS。
结果示于图4和表1。
[表1]
基于该结果,选择异槲皮素(IQ)、芦丁、绿原酸(CA)、和异鼠李素3-葡萄糖苷-7-鼠李糖苷(IR)作为翅果连翘叶乙醇提取物的功能成分,并确认了它们对BPH相关因子表达的影响。
5-2.翅果连翘叶乙醇提取物活性成分的效果的确认
确认了在实施例5-1中选择的四种类型的功能成分候选物(IQ、芦丁、CA和IR)对睾酮诱导的AR、5AR2和PSA表达水平的差异。该方法以与实施例2中相同的方式进行。
如图5a和5b所示,确认了在四种候选物中,异槲皮素表现出最优异的效果。
此外,如图6a和6b所示,确认了AR、PI3K和5AR2的表达根据异槲皮素的浓度而显著降低。
5-3.异槲皮素(IQ)的雄激素信号传导相关因子表达的确认
将BPH-1细胞用睾酮(100nM)处理以诱导细胞增殖,然后分别用25、50和100μM异槲皮素(IQ)以及25、50和100μg/mL的翅果连翘叶乙醇提取物处理24小时以确认对PI3K、细胞增殖因子PCNA和细胞周期蛋白D1表达的抑制作用。该方法以与实施例2相同的方式进行。PCNA是BPH发生时增加的因子,细胞周期蛋白D1对应于前列腺细胞中的细胞周期上调因子。
如图7a和7b所示,确认了根据异槲皮素和翅果连翘叶乙醇提取物的浓度,PI3K、PCNA和细胞周期蛋白D1的表达显著降低。
实施例6.根据翅果连翘提取时期的异槲皮素含量的确认
为了分析根据翅果连翘叶提取时期的活性成分异槲皮素,使用UPLC-MS。
如图8所示,确认了秋季含量(20.8849mg/g)高于春季含量(12.4916mg/g)。
即,确认了作为翅果连翘的功能性成分,显示出功能性和时间依赖性差异两者的异槲皮素是合适的。
实施例7.对BPH动物模型的效果的确认
7-1.翅果连翘提取物的BPH治疗效果的确认
为了确认翅果连翘提取物是否在体内也有效,制作BPH动物模型进行实验(见图9)。
如图10a至10e所示,确认了喂食秋季收获的翅果连翘叶提取物(ADLE)的小鼠具有比阳性对照显著更低的前列腺指数。具体而言,在ADLE施用组中,与BPH诱导模型相比,前列腺重量显著降低,前列腺重量与体重的比率也显著降低,前列腺上皮厚度与BPH模型相比也显著降低,并且与阳性对照锯棕榈和非那雄胺相比,ADLE效果更优。
此外,如图11a和11b所示,确认了ADLE摄取显著降低了前列腺组织中5AR2、SRC1、AR、ER和PSA的表达水平。
此外,如图11c所示,作为前列腺组织的H&E染色和前列腺上皮细胞观察的结果,确认了与对照(BPH)相比,在ADLE喂养组中,上皮细胞的厚度显著减小至CON水平。与阳性对照锯棕榈和非那雄胺相比,这是相似或极好的结果。
此外,如图11d所示,还确认了血清中的DHT水平显著降低,该结果支持通过降低导致前列腺生长和增大增加的DHT水平而引起的BPH的优异治疗效果。
此外,如图12a和12b所示,确认了ADLE摄取显著降低了前列腺组织中PI3K和p-AKT的表达水平。
此外,如图13a和13b所示,确认了ADLE摄取显著降低了前列腺组织中EGF、IGF-1、TGF-1β和VEGF的表达水平。
此外,如图14a和14b所示,确认了ADLE摄取显著降低了前列腺组织中PCNA和细胞周期蛋白D1的表达水平。
此外,如图14c所示,确认了ADLE摄取显著降低了前列腺组织中PCNA的表达水平。
此外,如图15a和15b所示,确认了ADLE摄取显著降低了前列腺组织中Bcl-2的表达水平,并且ADLE摄取显著增加了Bax的表达水平。
基于以上所有实施例,确认了翅果连翘提取物不仅显著改善雄激素受体和前列腺相关因子的水平,例如降低雄激素受体信号传导相关因子5AR2、SRC1、AR、ER和PSA的表达水平,而且对BPH动物模型也表现出显著的治疗作用。因此,可以看出本发明的翅果连翘提取物可用于雄激素受体相关疾病和前列腺相关疾病的治疗剂。
7-2.异槲皮素的BPH治疗效果的确认
除了实施例7-1之外,为了确认作为翅果连翘提取物的功能性成分的异槲皮素在体内是否有效,制作BPH动物模型进行实验。
如图16所示,作为口服施用低浓度(1mg/kg)和高浓度(10mg/kg)的异槲皮素的结果,确认了前列腺指数根据异槲皮素浓度而降低。具体而言,在异槲皮素施用组中,与BPH诱导模型相比,前列腺重量显著降低,前列腺重量与体重的比率也显著降低。
此外,如图17所示,确认了前列腺组织中AR、SRC-1、5AR2的表达水平根据异槲皮素摄取浓度而降低。
因此,确认了异槲皮素不仅显著改善雄激素受体和前列腺相关因子的水平,例如降低雄激素受体信号传导相关因子5AR2、SRC1、AR、ER和PSA的表达水平,而且表现出对BPH动物模型有显著的治疗效果。因此,可以看出,翅果连翘提取物的功能成分异槲皮素可用于雄激素受体相关疾病和前列腺相关疾病的治疗剂。
本领域的普通技术人员应当理解,本发明的上述描述是示例性的,并且在不脱离本发明的技术精神或本质特征的情况下,可以容易地将本文公开的示例性实施方案修改成其它具体形式。因此,上述示例性实施方案在任何方面都应被解释为说明性的而不是限制性的。
[工业实用性]
由于根据本发明的翅果连翘提取物或异槲皮素具有雄激素受体抑制活性,并且对良性前列腺增生(BPH)动物模型具有优异的治疗作用,其可广泛应用于雄激素受体相关疾病如BPH、雄激素依赖性脱发、排尿困难和前列腺癌,并且因此具有工业实用性。
Claims (14)
1.一种用于预防或治疗雄激素受体相关疾病的药物组合物,包含异槲皮素或翅果连翘(Abeliophyllum distichum)提取物作为活性成分。
2.根据权利要求1所述的药物组合物,其中所述提取物是使用选自由水、C1至C6醇、丙酮、乙醚、苯、氯仿、乙酸乙酯、二氯甲烷、己烷、环己烷、石油醚、亚临界流体和超临界流体组成的组中的一种或多种溶剂制备的提取物。
3.根据权利要求1所述的药物组合物,其中所述雄激素受体相关疾病为选自由前列腺癌、良性前列腺增生(BPH)、排尿困难和脱发组成的组中的一种或多种。
4.根据权利要求1所述的药物组合物,其中所述翅果连翘提取物包含异槲皮素。
5.根据权利要求1所述的药物组合物,其中所述翅果连翘提取物为翅果连翘叶提取物。
6.根据权利要求1所述的药物组合物,其中所述组合物抑制雄激素受体的表达。
7.根据权利要求1所述的药物组合物,其中所述组合物抑制选自由5α-还原酶2(5AR2)、类固醇受体共激活因子1(SRC1)、雌激素受体(ER)和前列腺特异性抗原(PSA)组成的组中的一种或多种雄激素信号传导相关因子。
8.根据权利要求1所述的药物组合物,其中所述组合物抑制PI3K/AKT信号传导通路。
9.一种用于预防或减轻雄激素受体相关疾病的食品组合物,包含异槲皮素或翅果连翘提取物作为活性成分。
10.根据权利要求9所述的食品组合物,其中所述食品组合物为健康功能食品。
11.根据权利要求9所述的食品组合物,其中所述雄激素受体相关疾病为选自由前列腺癌、良性前列腺增生(BPH)、排尿困难和脱发组成的组中的一种或多种。
12.一种预防或治疗雄激素受体相关疾病的方法,包括将包含异槲皮素或翅果连翘提取物作为活性成分的组合物施用于受试者。
13.包含异槲皮素或翅果连翘提取物作为活性成分的组合物用于预防或治疗雄激素受体相关疾病的用途。
14.异槲皮素或翅果连翘提取物用于生产预防或治疗雄激素受体相关疾病的药物的用途。
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR10-2020-0109845 | 2020-08-31 | ||
KR20200109845 | 2020-08-31 | ||
KR10-2021-0114027 | 2021-08-27 | ||
KR1020210114027A KR20220029474A (ko) | 2020-08-31 | 2021-08-27 | 미선나무 추출물을 유효성분으로 포함하는 안드로겐 수용체 관련 질환 치료용 약학적 조성물 |
PCT/KR2021/011564 WO2022045846A1 (ko) | 2020-08-31 | 2021-08-30 | 미선나무 추출물을 유효성분으로 포함하는 안드로겐 수용체 관련 질환 치료용 약학적 조성물 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN116056761A true CN116056761A (zh) | 2023-05-02 |
Family
ID=80355475
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202180053368.2A Pending CN116056761A (zh) | 2020-08-31 | 2021-08-30 | 包含翅果连翘提取物作为活性成分的用于治疗雄激素受体相关疾病的药物组合物 |
Country Status (5)
Country | Link |
---|---|
US (1) | US20230310477A1 (zh) |
EP (1) | EP4205756A1 (zh) |
JP (1) | JP2023539638A (zh) |
CN (1) | CN116056761A (zh) |
WO (1) | WO2022045846A1 (zh) |
Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH06199696A (ja) * | 1992-03-06 | 1994-07-19 | Yunie:Kk | 制癌・抗癌剤 |
KR20060059462A (ko) * | 2004-11-29 | 2006-06-02 | 학교법인 한림대학교 | 미선나무 추출물을 포함하는 항암제 |
CZ2014580A3 (cs) * | 2014-08-27 | 2016-03-09 | Walmark, A.S. | Doplněk stravy na bázi klikvy velkoplodé pro použití k oddálení biochemického návratu karcinomu prostaty |
US20160324911A1 (en) * | 2013-11-11 | 2016-11-10 | Naturex-DBS, LLC | Compositions and methods useful in treatment of lower urinary tract symptoms, benign prostatic hyperplasia, erectile dysfunction |
KR20170122317A (ko) * | 2016-04-26 | 2017-11-06 | 괴산군 | 미선나무 추출액을 이용한 탈모방지용 샴푸 조성물 |
CN109438536A (zh) * | 2018-10-29 | 2019-03-08 | 广东金骏康生物技术有限公司 | 一种异槲皮素及其衍生物的应用与制备方法 |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2001220313A (ja) * | 2000-02-09 | 2001-08-14 | Ichimaru Pharcos Co Ltd | 植物水蒸気蒸留水含有化粧料組成物 |
SG11202003122XA (en) * | 2017-10-19 | 2020-05-28 | Univ Yale | Inhibition of androgen receptor by extracts of medicinal herbs and compositions thereof |
KR102083294B1 (ko) * | 2017-11-17 | 2020-03-02 | 농업회사법인 엔제이바이오피아 주식회사 | 피부재생 효과를 갖는 미선나무 추출물 및 그 추출물을 함유하는 피부재생용 조성물 |
FR3091694B1 (fr) | 2019-01-11 | 2021-05-14 | Patrice Kandin | Dispositif de bobinage d'un tube souple |
KR20200109845A (ko) | 2019-03-14 | 2020-09-23 | 주식회사 두원 | 포제명찰 제작용 원단 |
-
2021
- 2021-08-30 JP JP2023513744A patent/JP2023539638A/ja active Pending
- 2021-08-30 EP EP21862142.3A patent/EP4205756A1/en active Pending
- 2021-08-30 US US18/043,093 patent/US20230310477A1/en active Pending
- 2021-08-30 CN CN202180053368.2A patent/CN116056761A/zh active Pending
- 2021-08-30 WO PCT/KR2021/011564 patent/WO2022045846A1/ko unknown
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH06199696A (ja) * | 1992-03-06 | 1994-07-19 | Yunie:Kk | 制癌・抗癌剤 |
KR20060059462A (ko) * | 2004-11-29 | 2006-06-02 | 학교법인 한림대학교 | 미선나무 추출물을 포함하는 항암제 |
US20160324911A1 (en) * | 2013-11-11 | 2016-11-10 | Naturex-DBS, LLC | Compositions and methods useful in treatment of lower urinary tract symptoms, benign prostatic hyperplasia, erectile dysfunction |
CZ2014580A3 (cs) * | 2014-08-27 | 2016-03-09 | Walmark, A.S. | Doplněk stravy na bázi klikvy velkoplodé pro použití k oddálení biochemického návratu karcinomu prostaty |
KR20170122317A (ko) * | 2016-04-26 | 2017-11-06 | 괴산군 | 미선나무 추출액을 이용한 탈모방지용 샴푸 조성물 |
CN109438536A (zh) * | 2018-10-29 | 2019-03-08 | 广东金骏康生物技术有限公司 | 一种异槲皮素及其衍生物的应用与制备方法 |
Also Published As
Publication number | Publication date |
---|---|
JP2023539638A (ja) | 2023-09-15 |
EP4205756A1 (en) | 2023-07-05 |
US20230310477A1 (en) | 2023-10-05 |
WO2022045846A1 (ko) | 2022-03-03 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US6428818B1 (en) | Tea catechin formulations and processes for making same | |
US6410061B1 (en) | Tea catechins as cancer specific proliferation inhibitors | |
TWI300352B (en) | Water soluble extract from plant of solanum genus and the preparation process thereof, and pharmaceutical composition containing the water soluble extract | |
JP2006508942A (ja) | アンドロゲンによって仲介される疾患を治療するためのエクオールの使用 | |
JP5934839B2 (ja) | ベルベノン誘導体を含有する退行性脳疾患治療または予防用薬学組成物 | |
JP2004501201A (ja) | ソホラ種からの抽出物、その製法およびその利用 | |
CN116056761A (zh) | 包含翅果连翘提取物作为活性成分的用于治疗雄激素受体相关疾病的药物组合物 | |
KR20210129565A (ko) | 전립선 비대증 또는 안드로겐성 탈모증 예방, 개선 또는 치료용 조성물 | |
KR102277092B1 (ko) | 죽엽 추출물을 유효성분으로 함유하는 남성 호르몬 의존성 질환의 예방, 개선 또는 치료용 조성물 | |
CN102266370B (zh) | 杭白菊中抗胃癌活性物质的半仿生提取方法 | |
KR101765141B1 (ko) | 스컬캅플라본 유도체 또는 이의 약학적으로 허용 가능한 염을 유효성분으로 함유하는 골질환의 예방 또는 치료용 약학적 조성물 | |
KR20220029474A (ko) | 미선나무 추출물을 유효성분으로 포함하는 안드로겐 수용체 관련 질환 치료용 약학적 조성물 | |
KR20120105403A (ko) | 식물 추출물을 포함하는 비만세포의 과립 분비 억제용 조성물 | |
KR20150037208A (ko) | 여성 폐경기 증후군 치료용 조성물 | |
US10292994B2 (en) | Bioactive fractions and compounds from Dalbergia sissoo for the prevention or treatment of osteo-health related disorders | |
US20210401918A1 (en) | Composition comprising combination of red clover extract and hops extract for improvement of menopausal disorder | |
KR101176618B1 (ko) | 아조엔을 유효성분으로 포함하는 엘엑스알-알파 과다 발현으로 인한 질병의 예방 및 치료용 조성물 | |
KR102168459B1 (ko) | 전립선 문제를 해결하기 위한 치료제로서 쿠르쿠마 망가 발 에 지프 추출물 | |
KR102146567B1 (ko) | 패랭이꽃 식물 추출물을 유효성분으로 포함하는 전립선 질환의 예방, 개선 또는 치료용 조성물 | |
KR101895850B1 (ko) | 벌씀바귀 추출물을 유효성분으로 함유하는 전립선 질환의 예방, 개선 또는 치료용 조성물 | |
KR102087662B1 (ko) | 4-[[4-[3-(사이클로프로필메톡시)-4-(디플루오로메톡시)페닐]-2-티아졸릴]아미노]페놀 화합물을 유효성분으로 포함하는 만성폐쇄성 폐질환의 예방 또는 치료용 조성물 | |
KR20110098994A (ko) | 리퀴리티게닌 또는 이소리퀴리티게닌을 유효성분으로 포함하는 엘엑스알-알파 과다 발현으로 인한 질병의 예방 또는 치료용 조성물 | |
KR101918023B1 (ko) | 미국개기장 추출물을 유효성분으로 함유하는 전립선 질환의 예방, 개선 또는 치료용 조성물 | |
US20240115537A1 (en) | Composition for preventing or treating breast cancer comprising compound derived from dendropanax morbiferus | |
US9283205B2 (en) | Method for extracting treatment ingredients for gastrointestinal diseases from bark of liriodendron tulipifera |
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 | ||
TA01 | Transfer of patent application right | ||
TA01 | Transfer of patent application right |
Effective date of registration: 20240229 Address after: Han Guozhongqingbeidao Applicant after: K-Biotechnology Co.,Ltd. Country or region after: Republic of Korea Address before: Han Guozhongqingbeidao Applicant before: KONKUK UNIVERSITY INDUSTRIAL COOPERATION Corp. Country or region before: Republic of Korea |