CN104427981A - 包含莱菔硫烷或莱菔硫烷前体和蕈类提取物或粉末的组合物 - Google Patents
包含莱菔硫烷或莱菔硫烷前体和蕈类提取物或粉末的组合物 Download PDFInfo
- Publication number
- CN104427981A CN104427981A CN201380035766.7A CN201380035766A CN104427981A CN 104427981 A CN104427981 A CN 104427981A CN 201380035766 A CN201380035766 A CN 201380035766A CN 104427981 A CN104427981 A CN 104427981A
- Authority
- CN
- China
- Prior art keywords
- sulforaphane
- powder
- enzyme
- extract
- composition
- 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.)
- Granted
Links
- SUVMJBTUFCVSAD-UHFFFAOYSA-N sulforaphane Chemical compound CS(=O)CCCCN=C=S SUVMJBTUFCVSAD-UHFFFAOYSA-N 0.000 title claims abstract description 398
- SUVMJBTUFCVSAD-JTQLQIEISA-N 4-Methylsulfinylbutyl isothiocyanate Natural products C[S@](=O)CCCCN=C=S SUVMJBTUFCVSAD-JTQLQIEISA-N 0.000 title claims abstract description 198
- 229960005559 sulforaphane Drugs 0.000 title claims abstract description 198
- 235000015487 sulforaphane Nutrition 0.000 title claims abstract description 198
- 239000000284 extract Substances 0.000 title claims abstract description 127
- 239000000843 powder Substances 0.000 title claims abstract description 116
- 239000000203 mixture Substances 0.000 title claims abstract description 94
- 235000001674 Agaricus brunnescens Nutrition 0.000 title claims abstract description 76
- 239000002243 precursor Substances 0.000 title claims abstract description 75
- 238000000034 method Methods 0.000 claims abstract description 93
- 102000004190 Enzymes Human genes 0.000 claims abstract description 92
- 108090000790 Enzymes Proteins 0.000 claims abstract description 92
- 240000001080 Grifola frondosa Species 0.000 claims abstract description 80
- 235000007710 Grifola frondosa Nutrition 0.000 claims abstract description 80
- 240000000599 Lentinula edodes Species 0.000 claims abstract description 72
- 235000001715 Lentinula edodes Nutrition 0.000 claims abstract description 71
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 94
- 230000000694 effects Effects 0.000 claims description 54
- 229930182475 S-glycoside Natural products 0.000 claims description 51
- 150000003569 thioglycosides Chemical class 0.000 claims description 51
- 229960005070 ascorbic acid Drugs 0.000 claims description 45
- 235000010323 ascorbic acid Nutrition 0.000 claims description 43
- 239000011668 ascorbic acid Substances 0.000 claims description 43
- 108010058651 thioglucosidase Proteins 0.000 claims description 38
- 239000012744 reinforcing agent Substances 0.000 claims description 37
- 238000006243 chemical reaction Methods 0.000 claims description 34
- 208000024891 symptom Diseases 0.000 claims description 23
- 239000002552 dosage form Substances 0.000 claims description 18
- 238000011282 treatment Methods 0.000 claims description 16
- 206010006187 Breast cancer Diseases 0.000 claims description 13
- 208000026310 Breast neoplasm Diseases 0.000 claims description 13
- 239000002702 enteric coating Substances 0.000 claims description 11
- 238000009505 enteric coating Methods 0.000 claims description 11
- 201000008275 breast carcinoma Diseases 0.000 claims description 10
- 230000002265 prevention Effects 0.000 claims description 7
- REFJWTPEDVJJIY-UHFFFAOYSA-N Quercetin Chemical compound C=1C(O)=CC(O)=C(C(C=2O)=O)C=1OC=2C1=CC=C(O)C(O)=C1 REFJWTPEDVJJIY-UHFFFAOYSA-N 0.000 claims description 6
- VFLDPWHFBUODDF-FCXRPNKRSA-N curcumin Chemical compound C1=C(O)C(OC)=CC(\C=C\C(=O)CC(=O)\C=C\C=2C=C(OC)C(O)=CC=2)=C1 VFLDPWHFBUODDF-FCXRPNKRSA-N 0.000 claims description 6
- WCGUUGGRBIKTOS-GPOJBZKASA-N (3beta)-3-hydroxyurs-12-en-28-oic acid Chemical compound C1C[C@H](O)C(C)(C)[C@@H]2CC[C@@]3(C)[C@]4(C)CC[C@@]5(C(O)=O)CC[C@@H](C)[C@H](C)[C@H]5C4=CC[C@@H]3[C@]21C WCGUUGGRBIKTOS-GPOJBZKASA-N 0.000 claims description 5
- PLSAJKYPRJGMHO-UHFFFAOYSA-N ursolic acid Natural products CC1CCC2(CCC3(C)C(C=CC4C5(C)CCC(O)C(C)(C)C5CCC34C)C2C1C)C(=O)O PLSAJKYPRJGMHO-UHFFFAOYSA-N 0.000 claims description 5
- 229940096998 ursolic acid Drugs 0.000 claims description 5
- 210000000582 semen Anatomy 0.000 claims description 4
- XFZJEEAOWLFHDH-UHFFFAOYSA-N (2R,2'R,3R,3'R,4R)-3,3',4',5,7-Pentahydroxyflavan(48)-3,3',4',5,7-pentahydroxyflavan Natural products C=12OC(C=3C=C(O)C(O)=CC=3)C(O)CC2=C(O)C=C(O)C=1C(C1=C(O)C=C(O)C=C1O1)C(O)C1C1=CC=C(O)C(O)=C1 XFZJEEAOWLFHDH-UHFFFAOYSA-N 0.000 claims description 3
- 229920002683 Glycosaminoglycan Polymers 0.000 claims description 3
- 244000025272 Persea americana Species 0.000 claims description 3
- 235000008673 Persea americana Nutrition 0.000 claims description 3
- CWEZAWNPTYBADX-UHFFFAOYSA-N Procyanidin Natural products OC1C(OC2C(O)C(Oc3c2c(O)cc(O)c3C4C(O)C(Oc5cc(O)cc(O)c45)c6ccc(O)c(O)c6)c7ccc(O)c(O)c7)c8c(O)cc(O)cc8OC1c9ccc(O)c(O)c9 CWEZAWNPTYBADX-UHFFFAOYSA-N 0.000 claims description 3
- MOJZMWJRUKIQGL-FWCKPOPSSA-N Procyanidin C2 Natural products O[C@@H]1[C@@H](c2cc(O)c(O)cc2)Oc2c([C@H]3[C@H](O)[C@@H](c4cc(O)c(O)cc4)Oc4c3c(O)cc(O)c4)c(O)cc(O)c2[C@@H]1c1c(O)cc(O)c2c1O[C@@H]([C@H](O)C2)c1cc(O)c(O)cc1 MOJZMWJRUKIQGL-FWCKPOPSSA-N 0.000 claims description 3
- ZVOLCUVKHLEPEV-UHFFFAOYSA-N Quercetagetin Natural products C1=C(O)C(O)=CC=C1C1=C(O)C(=O)C2=C(O)C(O)=C(O)C=C2O1 ZVOLCUVKHLEPEV-UHFFFAOYSA-N 0.000 claims description 3
- HWTZYBCRDDUBJY-UHFFFAOYSA-N Rhynchosin Natural products C1=C(O)C(O)=CC=C1C1=C(O)C(=O)C2=CC(O)=C(O)C=C2O1 HWTZYBCRDDUBJY-UHFFFAOYSA-N 0.000 claims description 3
- 235000012754 curcumin Nutrition 0.000 claims description 3
- 239000004148 curcumin Substances 0.000 claims description 3
- 229940109262 curcumin Drugs 0.000 claims description 3
- VFLDPWHFBUODDF-UHFFFAOYSA-N diferuloylmethane Natural products C1=C(O)C(OC)=CC(C=CC(=O)CC(=O)C=CC=2C=C(OC)C(O)=CC=2)=C1 VFLDPWHFBUODDF-UHFFFAOYSA-N 0.000 claims description 3
- MWDZOUNAPSSOEL-UHFFFAOYSA-N kaempferol Natural products OC1=C(C(=O)c2cc(O)cc(O)c2O1)c3ccc(O)cc3 MWDZOUNAPSSOEL-UHFFFAOYSA-N 0.000 claims description 3
- HGVVOUNEGQIPMS-UHFFFAOYSA-N procyanidin Chemical compound O1C2=CC(O)=CC(O)=C2C(O)C(O)C1(C=1C=C(O)C(O)=CC=1)OC1CC2=C(O)C=C(O)C=C2OC1C1=CC=C(O)C(O)=C1 HGVVOUNEGQIPMS-UHFFFAOYSA-N 0.000 claims description 3
- 229920002414 procyanidin Polymers 0.000 claims description 3
- 235000005875 quercetin Nutrition 0.000 claims description 3
- 229960001285 quercetin Drugs 0.000 claims description 3
- 241000167854 Bourreria succulenta Species 0.000 claims description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 2
- SEBFKMXJBCUCAI-UHFFFAOYSA-N NSC 227190 Natural products C1=C(O)C(OC)=CC(C2C(OC3=CC=C(C=C3O2)C2C(C(=O)C3=C(O)C=C(O)C=C3O2)O)CO)=C1 SEBFKMXJBCUCAI-UHFFFAOYSA-N 0.000 claims description 2
- 235000019693 cherries Nutrition 0.000 claims description 2
- 150000002337 glycosamines Chemical class 0.000 claims description 2
- 239000011777 magnesium Substances 0.000 claims description 2
- 229910052749 magnesium Inorganic materials 0.000 claims description 2
- 235000001055 magnesium Nutrition 0.000 claims description 2
- 235000002378 plant sterols Nutrition 0.000 claims description 2
- SEBFKMXJBCUCAI-HKTJVKLFSA-N silibinin Chemical compound C1=C(O)C(OC)=CC([C@@H]2[C@H](OC3=CC=C(C=C3O2)[C@@H]2[C@H](C(=O)C3=C(O)C=C(O)C=C3O2)O)CO)=C1 SEBFKMXJBCUCAI-HKTJVKLFSA-N 0.000 claims description 2
- 229960004245 silymarin Drugs 0.000 claims description 2
- 235000017700 silymarin Nutrition 0.000 claims description 2
- 229940088594 vitamin Drugs 0.000 claims description 2
- 229930003231 vitamin Natural products 0.000 claims description 2
- 235000013343 vitamin Nutrition 0.000 claims description 2
- 239000011782 vitamin Substances 0.000 claims description 2
- 150000003722 vitamin derivatives Chemical class 0.000 claims description 2
- 235000011299 Brassica oleracea var botrytis Nutrition 0.000 abstract description 29
- 240000003259 Brassica oleracea var. botrytis Species 0.000 abstract description 29
- 235000017647 Brassica oleracea var italica Nutrition 0.000 abstract description 25
- 240000008397 Ganoderma lucidum Species 0.000 abstract description 6
- 235000001637 Ganoderma lucidum Nutrition 0.000 abstract description 6
- 229940088598 enzyme Drugs 0.000 description 82
- 201000010099 disease Diseases 0.000 description 72
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 72
- 229920001503 Glucan Polymers 0.000 description 36
- 241000222336 Ganoderma Species 0.000 description 34
- 206010028980 Neoplasm Diseases 0.000 description 33
- AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical compound O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 description 32
- 229920002498 Beta-glucan Polymers 0.000 description 29
- 201000011510 cancer Diseases 0.000 description 29
- TWNIBLMWSKIRAT-VFUOTHLCSA-N levoglucosan Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@H]2CO[C@@H]1O2 TWNIBLMWSKIRAT-VFUOTHLCSA-N 0.000 description 28
- FYGDTMLNYKFZSV-URKRLVJHSA-N (2s,3r,4s,5s,6r)-2-[(2r,4r,5r,6s)-4,5-dihydroxy-2-(hydroxymethyl)-6-[(2r,4r,5r,6s)-4,5,6-trihydroxy-2-(hydroxymethyl)oxan-3-yl]oxyoxan-3-yl]oxy-6-(hydroxymethyl)oxane-3,4,5-triol Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1[C@@H](CO)O[C@@H](OC2[C@H](O[C@H](O)[C@H](O)[C@H]2O)CO)[C@H](O)[C@H]1O FYGDTMLNYKFZSV-URKRLVJHSA-N 0.000 description 18
- 229920000310 Alpha glucan Polymers 0.000 description 18
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 18
- 238000011160 research Methods 0.000 description 18
- 239000000262 estrogen Substances 0.000 description 17
- 229940011871 estrogen Drugs 0.000 description 17
- 101001109714 Rhizobium meliloti (strain 1021) NAD(P)H dehydrogenase (quinone) 1 Proteins 0.000 description 16
- 230000014509 gene expression Effects 0.000 description 15
- 238000002360 preparation method Methods 0.000 description 12
- 230000000968 intestinal effect Effects 0.000 description 11
- 210000004027 cell Anatomy 0.000 description 10
- 230000002079 cooperative effect Effects 0.000 description 10
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 9
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 9
- 230000001965 increasing effect Effects 0.000 description 9
- 239000000463 material Substances 0.000 description 9
- 239000002775 capsule Substances 0.000 description 8
- 238000002474 experimental method Methods 0.000 description 8
- 210000005075 mammary gland Anatomy 0.000 description 8
- -1 sulphoxylic acid thiocarbamate (sulfoxythiocarbamate) analog Chemical class 0.000 description 8
- 206010005003 Bladder cancer Diseases 0.000 description 7
- 101710149118 Quinone oxidoreductase 1 Proteins 0.000 description 7
- 230000002354 daily effect Effects 0.000 description 7
- 206010009944 Colon cancer Diseases 0.000 description 6
- 108020000284 NAD(P)H dehydrogenase (quinone) Proteins 0.000 description 6
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 239000000090 biomarker Substances 0.000 description 6
- 238000000576 coating method Methods 0.000 description 6
- 208000029742 colonic neoplasm Diseases 0.000 description 6
- 230000003203 everyday effect Effects 0.000 description 6
- 230000002496 gastric effect Effects 0.000 description 6
- 201000005112 urinary bladder cancer Diseases 0.000 description 6
- 240000007124 Brassica oleracea Species 0.000 description 5
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 5
- KBVQDUHOYIQWSM-BTVCFUMJSA-N N=C=S.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O Chemical compound N=C=S.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O KBVQDUHOYIQWSM-BTVCFUMJSA-N 0.000 description 5
- 240000001462 Pleurotus ostreatus Species 0.000 description 5
- 235000001603 Pleurotus ostreatus Nutrition 0.000 description 5
- 230000000996 additive effect Effects 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 239000011248 coating agent Substances 0.000 description 5
- 235000013305 food Nutrition 0.000 description 5
- 229930014626 natural product Natural products 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- 201000001514 prostate carcinoma Diseases 0.000 description 5
- 235000011302 Brassica oleracea Nutrition 0.000 description 4
- 241000219193 Brassicaceae Species 0.000 description 4
- 206010011732 Cyst Diseases 0.000 description 4
- 241000196324 Embryophyta Species 0.000 description 4
- 102000010911 Enzyme Precursors Human genes 0.000 description 4
- 108010062466 Enzyme Precursors Proteins 0.000 description 4
- 241000233866 Fungi Species 0.000 description 4
- 108010056771 Glucosidases Proteins 0.000 description 4
- 102000004366 Glucosidases Human genes 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 235000007685 Pleurotus columbinus Nutrition 0.000 description 4
- 208000006011 Stroke Diseases 0.000 description 4
- 238000007605 air drying Methods 0.000 description 4
- 230000001093 anti-cancer Effects 0.000 description 4
- 230000000259 anti-tumor effect Effects 0.000 description 4
- 230000003078 antioxidant effect Effects 0.000 description 4
- 230000000975 bioactive effect Effects 0.000 description 4
- 230000000711 cancerogenic effect Effects 0.000 description 4
- FDSDTBUPSURDBL-LOFNIBRQSA-N canthaxanthin Chemical compound CC=1C(=O)CCC(C)(C)C=1/C=C/C(/C)=C/C=C/C(/C)=C/C=C/C=C(C)C=CC=C(C)C=CC1=C(C)C(=O)CCC1(C)C FDSDTBUPSURDBL-LOFNIBRQSA-N 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 208000031513 cyst Diseases 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 210000001198 duodenum Anatomy 0.000 description 4
- 239000012530 fluid Substances 0.000 description 4
- 150000002540 isothiocyanates Chemical class 0.000 description 4
- 210000004185 liver Anatomy 0.000 description 4
- 230000004060 metabolic process Effects 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- 238000005507 spraying Methods 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 238000001291 vacuum drying Methods 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 241000437273 Auricularia cornea Species 0.000 description 3
- 241000282472 Canis lupus familiaris Species 0.000 description 3
- 235000014036 Castanea Nutrition 0.000 description 3
- 241001070941 Castanea Species 0.000 description 3
- 206010008190 Cerebrovascular accident Diseases 0.000 description 3
- 206010020772 Hypertension Diseases 0.000 description 3
- 239000002211 L-ascorbic acid Substances 0.000 description 3
- 235000000069 L-ascorbic acid Nutrition 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- 240000002769 Morchella esculenta Species 0.000 description 3
- 235000002779 Morchella esculenta Nutrition 0.000 description 3
- 201000003793 Myelodysplastic syndrome Diseases 0.000 description 3
- 244000252132 Pleurotus eryngii Species 0.000 description 3
- 235000001681 Pleurotus eryngii Nutrition 0.000 description 3
- 206010043118 Tardive Dyskinesia Diseases 0.000 description 3
- 241000121220 Tricholoma matsutake Species 0.000 description 3
- 240000006794 Volvariella volvacea Species 0.000 description 3
- 230000009286 beneficial effect Effects 0.000 description 3
- 229920001222 biopolymer Polymers 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 244000309464 bull Species 0.000 description 3
- 231100000357 carcinogen Toxicity 0.000 description 3
- 239000003183 carcinogenic agent Substances 0.000 description 3
- 210000001072 colon Anatomy 0.000 description 3
- 208000029078 coronary artery disease Diseases 0.000 description 3
- 230000002255 enzymatic effect Effects 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 239000002207 metabolite Substances 0.000 description 3
- 239000004014 plasticizer Substances 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 235000018102 proteins Nutrition 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 230000002685 pulmonary effect Effects 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 210000002784 stomach Anatomy 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 238000012546 transfer Methods 0.000 description 3
- 210000003932 urinary bladder Anatomy 0.000 description 3
- XQZVZULJKVALRI-UHFFFAOYSA-N 1-isothiocyanato-6-(methylsulfinyl)hexane Chemical compound CS(=O)CCCCCCN=C=S XQZVZULJKVALRI-UHFFFAOYSA-N 0.000 description 2
- 101710157142 2-methylene-furan-3-one reductase Proteins 0.000 description 2
- GOLORTLGFDVFDW-UHFFFAOYSA-N 3-(1h-benzimidazol-2-yl)-7-(diethylamino)chromen-2-one Chemical compound C1=CC=C2NC(C3=CC4=CC=C(C=C4OC3=O)N(CC)CC)=NC2=C1 GOLORTLGFDVFDW-UHFFFAOYSA-N 0.000 description 2
- 108091023020 Aldehyde Oxidase Proteins 0.000 description 2
- 102100036826 Aldehyde oxidase Human genes 0.000 description 2
- 201000001320 Atherosclerosis Diseases 0.000 description 2
- 241000221377 Auricularia Species 0.000 description 2
- 206010006298 Breast pain Diseases 0.000 description 2
- 101100356682 Caenorhabditis elegans rho-1 gene Proteins 0.000 description 2
- 241001249699 Capitata Species 0.000 description 2
- 208000024172 Cardiovascular disease Diseases 0.000 description 2
- 241000222511 Coprinus Species 0.000 description 2
- 208000011231 Crohn disease Diseases 0.000 description 2
- 102000002004 Cytochrome P-450 Enzyme System Human genes 0.000 description 2
- 108010015742 Cytochrome P-450 Enzyme System Proteins 0.000 description 2
- 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 2
- 108020005124 DNA Adducts Proteins 0.000 description 2
- 206010012289 Dementia Diseases 0.000 description 2
- 208000007342 Diabetic Nephropathies Diseases 0.000 description 2
- 206010014561 Emphysema Diseases 0.000 description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 2
- 241000282326 Felis catus Species 0.000 description 2
- 241001537207 Flammulina Species 0.000 description 2
- RUQCCAGSFPUGSZ-OBWQKADXSA-N Glucoraphanin Natural products C[S@](=O)CCCCC(=NS(=O)(=O)O)S[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O RUQCCAGSFPUGSZ-OBWQKADXSA-N 0.000 description 2
- 102100023469 Glutathione S-transferase theta-2 Human genes 0.000 description 2
- 241000725303 Human immunodeficiency virus Species 0.000 description 2
- 108010036012 Iodide peroxidase Proteins 0.000 description 2
- 241000149440 Lentinus tuber-regium Species 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- 208000006662 Mastodynia Diseases 0.000 description 2
- 102000013760 Microphthalmia-Associated Transcription Factor Human genes 0.000 description 2
- 108010050345 Microphthalmia-Associated Transcription Factor Proteins 0.000 description 2
- 241000117280 Naematelia aurantialba Species 0.000 description 2
- 241001597008 Nomeidae Species 0.000 description 2
- 241000237502 Ostreidae Species 0.000 description 2
- 108010019160 Pancreatin Proteins 0.000 description 2
- 241000282376 Panthera tigris Species 0.000 description 2
- 240000004370 Pastinaca sativa Species 0.000 description 2
- 235000017769 Pastinaca sativa subsp sativa Nutrition 0.000 description 2
- OOUTWVMJGMVRQF-DOYZGLONSA-N Phoenicoxanthin Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)C(=O)C(O)CC1(C)C)C=CC=C(/C)C=CC2=C(C)C(=O)CCC2(C)C OOUTWVMJGMVRQF-DOYZGLONSA-N 0.000 description 2
- 241000392443 Pleurotus citrinopileatus Species 0.000 description 2
- 101710189291 Quinone oxidoreductase Proteins 0.000 description 2
- 102100034576 Quinone oxidoreductase Human genes 0.000 description 2
- 238000010240 RT-PCR analysis Methods 0.000 description 2
- 241000700157 Rattus norvegicus Species 0.000 description 2
- MEFKEPWMEQBLKI-AIRLBKTGSA-N S-adenosyl-L-methioninate Chemical compound O[C@@H]1[C@H](O)[C@@H](C[S+](CC[C@H](N)C([O-])=O)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 MEFKEPWMEQBLKI-AIRLBKTGSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 229930182558 Sterol Natural products 0.000 description 2
- 102100023986 Sulfotransferase 1A1 Human genes 0.000 description 2
- 101710088873 Sulfotransferase 1A1 Proteins 0.000 description 2
- 241000244155 Taenia Species 0.000 description 2
- 102000002933 Thioredoxin Human genes 0.000 description 2
- 241001506047 Tremella Species 0.000 description 2
- 240000001717 Vaccinium macrocarpon Species 0.000 description 2
- 235000012545 Vaccinium macrocarpon Nutrition 0.000 description 2
- 235000004501 Volvariella volvacea Nutrition 0.000 description 2
- 244000195452 Wasabia japonica Species 0.000 description 2
- 235000000760 Wasabia japonica Nutrition 0.000 description 2
- GMMLNKINDDUDCF-JRWRFYLSSA-N [(2s,3r,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl] (1e)-5-[(r)-methylsulfinyl]-n-sulfooxypentanimidothioate Chemical compound C[S@@](=O)CCCC\C(=N/OS(O)(=O)=O)S[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O GMMLNKINDDUDCF-JRWRFYLSSA-N 0.000 description 2
- 208000002223 abdominal aortic aneurysm Diseases 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 229960001570 ademetionine Drugs 0.000 description 2
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- 230000000840 anti-viral effect Effects 0.000 description 2
- 210000000612 antigen-presenting cell Anatomy 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- 208000007474 aortic aneurysm Diseases 0.000 description 2
- 208000006673 asthma Diseases 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- 235000012682 canthaxanthin Nutrition 0.000 description 2
- 239000001659 canthaxanthin Substances 0.000 description 2
- 229940008033 canthaxanthin Drugs 0.000 description 2
- AIXAANGOTKPUOY-UHFFFAOYSA-N carbachol Chemical compound [Cl-].C[N+](C)(C)CCOC(N)=O AIXAANGOTKPUOY-UHFFFAOYSA-N 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 208000027157 chronic rhinosinusitis Diseases 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 239000013068 control sample Substances 0.000 description 2
- 235000004634 cranberry Nutrition 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 208000033679 diabetic kidney disease Diseases 0.000 description 2
- DOIRQSBPFJWKBE-UHFFFAOYSA-N dibutyl phthalate Chemical compound CCCCOC(=O)C1=CC=CC=C1C(=O)OCCCC DOIRQSBPFJWKBE-UHFFFAOYSA-N 0.000 description 2
- 235000015872 dietary supplement Nutrition 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 210000000981 epithelium Anatomy 0.000 description 2
- 230000001076 estrogenic effect Effects 0.000 description 2
- 125000004383 glucosinolate group Chemical group 0.000 description 2
- 150000004676 glycans Chemical class 0.000 description 2
- 230000007365 immunoregulation Effects 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 235000015110 jellies Nutrition 0.000 description 2
- 239000008274 jelly Substances 0.000 description 2
- 208000017169 kidney disease Diseases 0.000 description 2
- 108010030727 lens intermediate filament proteins Proteins 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 210000002540 macrophage Anatomy 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 201000006417 multiple sclerosis Diseases 0.000 description 2
- 210000000822 natural killer cell Anatomy 0.000 description 2
- 230000004770 neurodegeneration Effects 0.000 description 2
- 208000015122 neurodegenerative disease Diseases 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 235000016709 nutrition Nutrition 0.000 description 2
- 230000035764 nutrition Effects 0.000 description 2
- 201000008482 osteoarthritis Diseases 0.000 description 2
- 235000020636 oyster Nutrition 0.000 description 2
- 229940055695 pancreatin Drugs 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 229920001282 polysaccharide Polymers 0.000 description 2
- 239000005017 polysaccharide Substances 0.000 description 2
- 210000002307 prostate Anatomy 0.000 description 2
- 239000003223 protective agent Substances 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 125000006850 spacer group Chemical group 0.000 description 2
- 150000003432 sterols Chemical class 0.000 description 2
- 235000003702 sterols Nutrition 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 108060008226 thioredoxin Proteins 0.000 description 2
- 229940094937 thioredoxin Drugs 0.000 description 2
- 230000000451 tissue damage Effects 0.000 description 2
- 231100000827 tissue damage Toxicity 0.000 description 2
- URAYPUMNDPQOKB-UHFFFAOYSA-N triacetin Chemical compound CC(=O)OCC(OC(C)=O)COC(C)=O URAYPUMNDPQOKB-UHFFFAOYSA-N 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- ADHNUPOJJCKWRT-JLXBFWJWSA-N (2e,4e)-octadeca-2,4-dienoic acid Chemical compound CCCCCCCCCCCCC\C=C\C=C\C(O)=O ADHNUPOJJCKWRT-JLXBFWJWSA-N 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- WOAHJDHKFWSLKE-UHFFFAOYSA-N 1,2-benzoquinone Chemical compound O=C1C=CC=CC1=O WOAHJDHKFWSLKE-UHFFFAOYSA-N 0.000 description 1
- PORPENFLTBBHSG-MGBGTMOVSA-N 1,2-dihexadecanoyl-sn-glycerol-3-phosphate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(O)=O)OC(=O)CCCCCCCCCCCCCCC PORPENFLTBBHSG-MGBGTMOVSA-N 0.000 description 1
- TZCPCKNHXULUIY-RGULYWFUSA-N 1,2-distearoyl-sn-glycero-3-phosphoserine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OC[C@H](N)C(O)=O)OC(=O)CCCCCCCCCCCCCCCCC TZCPCKNHXULUIY-RGULYWFUSA-N 0.000 description 1
- UEKJGWMAHPEGHJ-UHFFFAOYSA-N 1-isothiocyanato-4-methylsulfinylbutane Chemical compound CS(=O)CCCCN=C=S.CS(=O)CCCCN=C=S UEKJGWMAHPEGHJ-UHFFFAOYSA-N 0.000 description 1
- WXYAXKKXIGHXDS-UHFFFAOYSA-N 1-isothiocyanatohexane Chemical compound CCCCCCN=C=S WXYAXKKXIGHXDS-UHFFFAOYSA-N 0.000 description 1
- 239000001638 1-isothiocyanatohexane Substances 0.000 description 1
- 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 1
- PFRQBZFETXBLTP-RCIYGOBDSA-N 2-[(2e,6e,10e,14e,18e)-3,7,11,15,19,23-hexamethyltetracosa-2,6,10,14,18,22-hexaen-1-yl]-3-methyl-1,4-dihydronaphthalene-1,4-dione Chemical compound C1=CC=C2C(=O)C(C/C=C(C)/CC/C=C(C)/CC/C=C(C)/CC/C=C(C)/CC/C=C(C)/CCC=C(C)C)=C(C)C(=O)C2=C1 PFRQBZFETXBLTP-RCIYGOBDSA-N 0.000 description 1
- MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- FGYQUFZANKOISC-UHFFFAOYSA-N 5-methylsulfinylpentyl nitrile Chemical compound CS(=O)CCCCC#N FGYQUFZANKOISC-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- 102000005751 Alcohol Oxidoreductases Human genes 0.000 description 1
- 108010031132 Alcohol Oxidoreductases Proteins 0.000 description 1
- 208000024827 Alzheimer disease Diseases 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
- 244000144725 Amygdalus communis Species 0.000 description 1
- 235000011437 Amygdalus communis Nutrition 0.000 description 1
- 240000003291 Armoracia rusticana Species 0.000 description 1
- 235000011330 Armoracia rusticana Nutrition 0.000 description 1
- 235000000023 Auricularia auricula Nutrition 0.000 description 1
- 240000005710 Auricularia polytricha Species 0.000 description 1
- 235000017166 Bambusa arundinacea Nutrition 0.000 description 1
- 235000017491 Bambusa tulda Nutrition 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 235000003899 Brassica oleracea var acephala Nutrition 0.000 description 1
- 235000011301 Brassica oleracea var capitata Nutrition 0.000 description 1
- 235000004221 Brassica oleracea var gemmifera Nutrition 0.000 description 1
- 235000001169 Brassica oleracea var oleracea Nutrition 0.000 description 1
- 244000308368 Brassica oleracea var. gemmifera Species 0.000 description 1
- 102000049320 CD36 Human genes 0.000 description 1
- 108010045374 CD36 Antigens Proteins 0.000 description 1
- 229920000018 Callose Polymers 0.000 description 1
- 241000282836 Camelus dromedarius Species 0.000 description 1
- 208000005623 Carcinogenesis Diseases 0.000 description 1
- 229920000623 Cellulose acetate phthalate Polymers 0.000 description 1
- 229920002567 Chondroitin Polymers 0.000 description 1
- 206010009137 Chronic sinusitis Diseases 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 229920002785 Croscarmellose sodium Polymers 0.000 description 1
- 244000163122 Curcuma domestica Species 0.000 description 1
- 102000018832 Cytochromes Human genes 0.000 description 1
- 108010052832 Cytochromes Proteins 0.000 description 1
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 241000283073 Equus caballus Species 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- 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 1
- 241000390128 Eutrema Species 0.000 description 1
- 241000749669 Eutrema yunnanense Species 0.000 description 1
- 101150048700 Fcgr3 gene Proteins 0.000 description 1
- 239000004606 Fillers/Extenders Substances 0.000 description 1
- 240000006499 Flammulina velutipes Species 0.000 description 1
- 235000016640 Flammulina velutipes Nutrition 0.000 description 1
- 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 1
- 102100039696 Glutamate-cysteine ligase catalytic subunit Human genes 0.000 description 1
- 101710102075 Glutathione S-transferase 1 Proteins 0.000 description 1
- 101710169602 Glutathione S-transferase theta-2 Proteins 0.000 description 1
- 102000005720 Glutathione transferase Human genes 0.000 description 1
- 108010070675 Glutathione transferase Proteins 0.000 description 1
- JZNWSCPGTDBMEW-UHFFFAOYSA-N Glycerophosphorylethanolamin Natural products NCCOP(O)(=O)OCC(O)CO JZNWSCPGTDBMEW-UHFFFAOYSA-N 0.000 description 1
- ZWZWYGMENQVNFU-UHFFFAOYSA-N Glycerophosphorylserin Natural products OC(=O)C(N)COP(O)(=O)OCC(O)CO ZWZWYGMENQVNFU-UHFFFAOYSA-N 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- 102100028006 Heme oxygenase 1 Human genes 0.000 description 1
- 101001034527 Homo sapiens Glutamate-cysteine ligase catalytic subunit Proteins 0.000 description 1
- 101001079623 Homo sapiens Heme oxygenase 1 Proteins 0.000 description 1
- 101000588302 Homo sapiens Nuclear factor erythroid 2-related factor 2 Proteins 0.000 description 1
- 101000795074 Homo sapiens Tryptase alpha/beta-1 Proteins 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 1
- 102100034343 Integrase Human genes 0.000 description 1
- 102000015271 Intercellular Adhesion Molecule-1 Human genes 0.000 description 1
- 108010064593 Intercellular Adhesion Molecule-1 Proteins 0.000 description 1
- 102000011845 Iodide peroxidase Human genes 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- 229920001491 Lentinan Polymers 0.000 description 1
- 108090000364 Ligases Proteins 0.000 description 1
- 102000003960 Ligases Human genes 0.000 description 1
- OYHQOLUKZRVURQ-HZJYTTRNSA-N Linoleic acid Chemical compound CCCCC\C=C/C\C=C/CCCCCCCC(O)=O OYHQOLUKZRVURQ-HZJYTTRNSA-N 0.000 description 1
- 229920002774 Maltodextrin Polymers 0.000 description 1
- 239000005913 Maltodextrin Substances 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 206010027458 Metastases to lung Diseases 0.000 description 1
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- 102100022365 NAD(P)H dehydrogenase [quinone] 1 Human genes 0.000 description 1
- 101710095135 NAD(P)H dehydrogenase [quinone] 1 Proteins 0.000 description 1
- ACFIXJIJDZMPPO-NNYOXOHSSA-N NADPH Chemical compound C1=CCC(C(=O)N)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]2[C@H]([C@@H](OP(O)(O)=O)[C@@H](O2)N2C3=NC=NC(N)=C3N=C2)O)O1 ACFIXJIJDZMPPO-NNYOXOHSSA-N 0.000 description 1
- 235000017879 Nasturtium officinale Nutrition 0.000 description 1
- 240000005407 Nasturtium officinale Species 0.000 description 1
- 102100031701 Nuclear factor erythroid 2-related factor 2 Human genes 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 241000282320 Panthera leo Species 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 101710132584 Peroxidase 3 Proteins 0.000 description 1
- 244000082204 Phyllostachys viridis Species 0.000 description 1
- 235000015334 Phyllostachys viridis Nutrition 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- 244000272459 Silybum marianum Species 0.000 description 1
- 235000010841 Silybum marianum Nutrition 0.000 description 1
- 241000220261 Sinapis Species 0.000 description 1
- 239000004902 Softening Agent Substances 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 101000953909 Streptomyces viridifaciens Isobutylamine N-hydroxylase Proteins 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 101150071209 TPSB2 gene Proteins 0.000 description 1
- 102000001639 Thioredoxin Reductase 1 Human genes 0.000 description 1
- 108010093836 Thioredoxin Reductase 1 Proteins 0.000 description 1
- DOOTYTYQINUNNV-UHFFFAOYSA-N Triethyl citrate Chemical compound CCOC(=O)CC(O)(C(=O)OCC)CC(=O)OCC DOOTYTYQINUNNV-UHFFFAOYSA-N 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 102100029639 Tryptase alpha/beta-1 Human genes 0.000 description 1
- 206010061391 Tuberculosis of central nervous system Diseases 0.000 description 1
- 241000282458 Ursus sp. Species 0.000 description 1
- 235000002118 Vaccinium oxycoccus Nutrition 0.000 description 1
- 229930003268 Vitamin C Natural products 0.000 description 1
- GMMLNKINDDUDCF-RFOBZYEESA-N [(2s,3r,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl] (1e)-5-methylsulfinyl-n-sulfooxypentanimidothioate Chemical compound CS(=O)CCCC\C(=N/OS(O)(=O)=O)S[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O GMMLNKINDDUDCF-RFOBZYEESA-N 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 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 1
- ZUAAPNNKRHMPKG-UHFFFAOYSA-N acetic acid;butanedioic acid;methanol;propane-1,2-diol Chemical compound OC.CC(O)=O.CC(O)CO.OC(=O)CCC(O)=O ZUAAPNNKRHMPKG-UHFFFAOYSA-N 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 239000003463 adsorbent Substances 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 235000020224 almond Nutrition 0.000 description 1
- 229940043376 ammonium acetate Drugs 0.000 description 1
- 235000019257 ammonium acetate Nutrition 0.000 description 1
- ARCGXLSVLAOJQL-UHFFFAOYSA-N anhydrous trimellitic acid Natural products OC(=O)C1=CC=C(C(O)=O)C(C(O)=O)=C1 ARCGXLSVLAOJQL-UHFFFAOYSA-N 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 230000002001 anti-metastasis Effects 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 230000001028 anti-proliverative effect Effects 0.000 description 1
- 239000002518 antifoaming agent Substances 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 229940072107 ascorbate Drugs 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 235000015241 bacon Nutrition 0.000 description 1
- 239000011425 bamboo Substances 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 1
- 229960002246 beta-d-glucopyranose Drugs 0.000 description 1
- 235000013361 beverage Nutrition 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- IISBACLAFKSPIT-UHFFFAOYSA-N bisphenol A Chemical compound C=1C=C(O)C=CC=1C(C)(C)C1=CC=C(O)C=C1 IISBACLAFKSPIT-UHFFFAOYSA-N 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 210000000069 breast epithelial cell Anatomy 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 230000036952 cancer formation Effects 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 229940063834 carboxymethylcellulose sodium Drugs 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 231100000315 carcinogenic Toxicity 0.000 description 1
- 210000000748 cardiovascular system Anatomy 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 229920002301 cellulose acetate Polymers 0.000 description 1
- 229940081734 cellulose acetate phthalate Drugs 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 208000008501 central nervous system tuberculosis Diseases 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 235000015111 chews Nutrition 0.000 description 1
- DLGJWSVWTWEWBJ-HGGSSLSASA-N chondroitin Chemical compound CC(O)=N[C@@H]1[C@H](O)O[C@H](CO)[C@H](O)[C@@H]1OC1[C@H](O)[C@H](O)C=C(C(O)=O)O1 DLGJWSVWTWEWBJ-HGGSSLSASA-N 0.000 description 1
- 210000004252 chorionic villi Anatomy 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 208000037976 chronic inflammation Diseases 0.000 description 1
- 208000037893 chronic inflammatory disorder Diseases 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 229920002770 condensed tannin Polymers 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 229960000913 crospovidone Drugs 0.000 description 1
- 235000003373 curcuma longa Nutrition 0.000 description 1
- 230000001120 cytoprotective effect Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 230000000593 degrading effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000003596 drug target Substances 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 239000003974 emollient agent Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000037149 energy metabolism Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 238000013265 extended release Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000004088 foaming agent Substances 0.000 description 1
- 210000004211 gastric acid Anatomy 0.000 description 1
- 210000003736 gastrointestinal content Anatomy 0.000 description 1
- 230000000762 glandular Effects 0.000 description 1
- 229960002442 glucosamine Drugs 0.000 description 1
- 229960001031 glucose Drugs 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 1
- 235000003969 glutathione Nutrition 0.000 description 1
- 229960003180 glutathione Drugs 0.000 description 1
- 239000001087 glyceryl triacetate Substances 0.000 description 1
- 235000013773 glyceryl triacetate Nutrition 0.000 description 1
- 239000003979 granulating agent Substances 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 244000005709 gut microbiome Species 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000002607 hemopoietic effect Effects 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 210000003630 histaminocyte Anatomy 0.000 description 1
- 238000002013 hydrophilic interaction chromatography Methods 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 201000001421 hyperglycemia Diseases 0.000 description 1
- 210000003405 ileum Anatomy 0.000 description 1
- 230000002519 immonomodulatory effect Effects 0.000 description 1
- 230000036737 immune function Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 238000012744 immunostaining Methods 0.000 description 1
- 238000009169 immunotherapy Methods 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 102000017712 iodothyronine deiodinase Human genes 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 210000001630 jejunum Anatomy 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 229940115286 lentinan Drugs 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 229920005610 lignin Polymers 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- OYHQOLUKZRVURQ-IXWMQOLASA-N linoleic acid Natural products CCCCC\C=C/C\C=C\CCCCCCCC(O)=O OYHQOLUKZRVURQ-IXWMQOLASA-N 0.000 description 1
- 235000020778 linoleic acid Nutrition 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 229940035034 maltodextrin Drugs 0.000 description 1
- 230000000873 masking effect Effects 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000037323 metabolic rate Effects 0.000 description 1
- 229940117841 methacrylic acid copolymer Drugs 0.000 description 1
- 229920003145 methacrylic acid copolymer Polymers 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 210000001589 microsome Anatomy 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- 201000000050 myeloid neoplasm Diseases 0.000 description 1
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 150000002885 octadecanoids Chemical class 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 150000002898 organic sulfur compounds Chemical group 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 230000036542 oxidative stress Effects 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 1
- 150000008104 phosphatidylethanolamines Chemical class 0.000 description 1
- 229940067626 phosphatidylinositols Drugs 0.000 description 1
- 150000003905 phosphatidylinositols Chemical class 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 229940068065 phytosterols Drugs 0.000 description 1
- 229940068196 placebo Drugs 0.000 description 1
- 239000000902 placebo Substances 0.000 description 1
- 210000002826 placenta Anatomy 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 230000007096 poisonous effect Effects 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000307 polymer substrate Polymers 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229950008882 polysorbate Drugs 0.000 description 1
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
- 231100000586 procarcinogen Toxicity 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 239000000583 progesterone congener Substances 0.000 description 1
- 230000037209 prostate health Effects 0.000 description 1
- 235000004252 protein component Nutrition 0.000 description 1
- 208000008128 pulmonary tuberculosis Diseases 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 230000007115 recruitment Effects 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 210000004994 reproductive system Anatomy 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 230000036559 skin health Effects 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 229940080313 sodium starch Drugs 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 230000035882 stress Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- LELAOEBVZLPXAZ-UHFFFAOYSA-N sulfpraphane Natural products CS(=O)CCCN=C=S LELAOEBVZLPXAZ-UHFFFAOYSA-N 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 229960002622 triacetin Drugs 0.000 description 1
- 239000001069 triethyl citrate Substances 0.000 description 1
- VMYFZRTXGLUXMZ-UHFFFAOYSA-N triethyl citrate Natural products CCOC(=O)C(O)(C(=O)OCC)C(=O)OCC VMYFZRTXGLUXMZ-UHFFFAOYSA-N 0.000 description 1
- 235000013769 triethyl citrate Nutrition 0.000 description 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
- 125000005591 trimellitate group Chemical group 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 230000001810 trypsinlike Effects 0.000 description 1
- 230000005760 tumorsuppression Effects 0.000 description 1
- 208000010570 urinary bladder carcinoma Diseases 0.000 description 1
- 210000002229 urogenital system Anatomy 0.000 description 1
- 210000003556 vascular endothelial cell Anatomy 0.000 description 1
- 235000019154 vitamin C Nutrition 0.000 description 1
- 239000011718 vitamin C Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/47—Hydrolases (3) acting on glycosyl compounds (3.2), e.g. cellulases, lactases
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/095—Sulfur, selenium, or tellurium compounds, e.g. thiols
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/194—Carboxylic acids, e.g. valproic acid having two or more carboxyl groups, e.g. succinic, maleic or phthalic acid
-
- 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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/26—Cyanate or isocyanate esters; Thiocyanate or isothiocyanate esters
-
- 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
- A61K31/275—Nitriles; Isonitriles
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/357—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
- A61K31/375—Ascorbic acid, i.e. vitamin C; Salts thereof
-
- 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
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
-
- 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
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/716—Glucans
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
-
- 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
- A61K36/06—Fungi, e.g. yeasts
-
- 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
- A61K36/06—Fungi, e.g. yeasts
- A61K36/07—Basidiomycota, e.g. Cryptococcus
-
- 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)
- A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
-
- 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)
- A61K36/31—Brassicaceae or Cruciferae (Mustard family), e.g. broccoli, cabbage or kohlrabi
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/42—Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y302/00—Hydrolases acting on glycosyl compounds, i.e. glycosylases (3.2)
- C12Y302/01—Glycosidases, i.e. enzymes hydrolysing O- and S-glycosyl compounds (3.2.1)
- C12Y302/01147—Thioglucosidase (3.2.1.147), i.e. myrosinase
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
Abstract
本发明涉及莱菔硫烷前体、能够将莱菔硫烷前体转化为莱菔硫烷的酶、酶增强剂、以及蕈类(优选灰树花、香菇或灵芝)提取物或粉末的组合。本发明还涉及莱菔硫烷或其衍生物和蕈类(优选灰树花、香菇或灵芝)提取物或粉末的组合。本发明还涉及西兰花提取物或粉末和蕈类(优选灰树花、香菇或灵芝)提取物或粉末的组合。本发明提供涉及这些组合的组合物和方法。
Description
本申请要求下列申请的优先权:于2012年7月5日提交的美国临时专利申请第61/668,328号;于2012年7月5日提交的美国临时专利申请第61/668,342号;于2012年7月5日提交的美国临时专利申请第61/668,386号;于2012年7月5日提交的美国临时专利申请第61/668,396号;于2012年7月5日提交的美国临时专利申请第61/668,364号;于2012年7月5日提交的美国临时专利申请第61/668,374号;和于2013年3月15日提交的美国临时专利申请第61/794,417号,其中的每一个申请均以其全部内容通过引用并入本文。
技术领域
本发明涉及莱菔硫烷前体、能够将莱菔硫烷前体转化为莱菔硫烷的酶、酶增强剂、以及蕈类(mushroom)(优选灰树花、香菇或灵芝)提取物或粉末的组合。本发明还涉及莱菔硫烷或其衍生物和蕈类(优选灰树花、香菇或灵芝)提取物或粉末的组合。本发明还涉及西兰花(broccoli)提取物或粉末和蕈类(优选灰树花、香菇或灵芝)提取物或粉末的组合。本发明提供涉及这些组合的组合物和方法。
背景技术
天然产物的使用越来越受到人和伴侣动物的喜爱。这些天然产物中的一些被纳入膳食补充剂和医用食品。本领域需要可用作化学保护剂和/或抗氧剂的补充剂。此外,本领域需要可用于与乳腺相关的病症(conditions)和疾病的药物组合物和膳食补充剂。
通过使用天然产物进行化学保护正在发展成为安全、有效、低廉、易得且实际的方法以预防或减少许多影响到人和驯化动物的病症的发生。已知能在分子水平上损伤细胞的致癌物常以无毒前体被摄取和吸入。这些无毒前体随后可在体内转化为致癌物质。化学保护剂如能激活解毒酶或它们的辅助因子的天然物质,能对抗和允许消除或增强其它天然存在的防御如免疫系统。
某些天然产物具有抗氧化活性。氧化应激在衰老、神经退行性疾病的进程以及生理创伤,如缺血中起重要作用。抗氧剂能减少或抑制重要生物分子的氧化并可以在治疗、预防、或减少癌症、冠心病、中风和神经退行性疾病的发生中起作用,而阿尔茨海默病(Alzheimer's Disease)、痴呆(dementia),以及中风是受氧化应激影响的病症的实例。
癌症大多被认为是暴露于环境挑战—无论是来自内部(即—雌激素、孕激素)还是来自外部(即—来自塑料中的双酚A(BPA))—和慢性炎症的结果。幸运的是,来自环境挑战的损伤可经由在我们体内的许多细胞类型中发现的II期化学保护酶的复杂网络消除。众所周知雌激素和它们的代谢物可导致乳腺组织增生和肿瘤。更糟地,醌雌激素代谢物能够进入乳腺组织并转移到管状和腺状上皮细胞的细胞核中。在那里,它们与DNA结合形成醌雌激素DNA加合物,导致下游突变。这些突变被认为是引起肿瘤的真正基础:癌症引发。
幸运的是,一种特殊的II期酶NAD(P)H:醌氧化还原酶(NQO1)可带走危险的和高反应性的醌雌激素并将它们代谢为易从体内移除的惰性化学物质。因此,降低癌症发病率的主要机制为诱导包括NQO1在内的保护性II期酶。增加的NQO1水平可有效地治疗、预防由高水平的醌雌激素引起的任何病症;修复与由高水平的醌雌激素引起的任何病症相关的症状;减少与由高水平的醌雌激素引起的任何病症相关的症状的发生;减少与由高水平的醌雌激素引起的任何病症相关的症状。醌雌激素的实例包括但不限于雌激素的儿茶酚醌。醌雌激素在以下参考文献中有描述:Nutter et al.Chem Res Toxicol,1994,7:23-28;Cavalieri et al.Ann N Y Acad Sci,2006;1089:286-301;Bolton et al.Chem Res Toxicol,2008,21(1):93-101;和Cavalieri et al.,Biochimica etBiophysica Acta,2006,1766:63-78,每篇参考文献均以其全部内容通过引用并入本文。
认为具有化学保护和抗氧化性质的天然产物的一个实例为莱菔硫烷(sulforaphane)。莱菔硫烷是有机硫化合物,也被称为1-异硫氰酸根合-4-甲基亚磺酰基丁烷(1-isothiocyanato-4-methylsulfinylbutane)。莱菔硫烷前体,硫代葡萄糖苷(glucoraphanin),可从十字花科(Brassicaceae)植物如西兰花、球芽甘蓝(brussels sprouts)和卷心菜(cabbage)中获得。但是,必须消耗大量植物以便获得足够用于化学保护的水平。硫代葡萄糖苷通过称作黑芥子硫苷酸酶的硫葡糖苷酶转化为莱菔硫烷,黑芥子硫苷酸酶存在于各种外源性来源如十字花科植物和内源性肠道微生物群中。但是,摄取硫代葡萄糖苷后,并非所有动物都能将其转化为莱菔硫烷,很可能由于微生物种群和整体健康的差异。此外,在酸性环境如胃中,硫代葡萄糖苷可被转化为惰性代谢物。活性代谢物莱菔硫烷诱导核红细胞系-2-相关因子(Nrf2),该因子又上调II期解毒酶和细胞保护酶如谷胱甘肽S-转移酶、NAD(P)H:醌氧化还原酶(NQO1)以及血红素-加氧酶-1(HO-1)的生成。莱菔硫烷已被认为诱导这些酶的生成而不显著改变P-450细胞色素酶的合成。II期酶的上调被认为在许多生物活性中起作用,包括保护脑不受细胞毒性,保护肝不受脂肪堆积的毒性效应,以及对各种其它组织的解毒作用。
莱菔硫烷和其前体硫代葡萄糖苷已被广泛研究。Shapiro等(Nutrition andCancer,(2006),Vol.55(1),pp.53-62)讨论测定西兰花芽葡萄糖异硫氰酸酯(glucosinolates)和异硫氰酸酯的安全性、耐受性以及代谢的I期临床研究。Shapiro等讨论在健康人类受试者中进行的含有葡萄糖异硫氰酸酯如硫代葡萄糖苷或异硫氰酸酯如莱菔硫烷的芽提取物的安慰剂对照、双盲、随机临床研究。研究发现给予这些物质没有导致系统的、临床上显著的不良作用。Ye等(Clinica Chimica Acta,200,316:43-53)讨论西兰花芽异硫氰酸酯在人体中的药代动力学。
一些蕈类已被应用或研究其药用功效。这些“药用蕈类(medicinalmushrooms)”被认为具有有益性质,如抗病毒、抗微生物、抗癌、抗高血糖和/或抗炎活性。药用蕈类的实例包括灰树花、香菇、灵芝、褐菇(cremini)、杏仁菇(almond)、栗菇(chestnut)、木耳(wood ear)、云耳(cloud ear)、牛肝菌(porcini)、墨汁鬼伞(ink cap)、yarta gunbu、金针菇(enokitake)、占地菇(shemeji)、虎奶菌(tiger milk)、羊肚菌(morel)、竹菇(bamboo)、黄金菇(golden oyster)、粉红平菇(pink oyster)、杏鲍菇(king oyster)、平菇(hiratake)、菜花(cauliflower)、银耳(white jelly)、金耳(golden jelly)、松茸(matsutake)、墨西哥松露(Mexicantruffle)和草菇(straw mushroom)。
灰树花(maitake mushroom)(Grifola frondosa)为食用菌,广泛用作食物和传统药物以提高免疫功能和治疗癌症。灰树花,其含有葡聚糖,被认为具有有益性质,如抗肿瘤和免疫调节作用。已存在含有葡聚糖如蛋白结合β-葡聚糖作为活性组分的标准灰树花提取物。β1,6-葡聚糖是一种蛋白结合多糖,已被鉴定为灰树花中的活性成分。已证实灰树花具有抗肿瘤作用,体外抑制肿瘤转移。在一项研究中,在使用灰树花提取物的半数受试者中观察到肿瘤消退或症状明显改善。在绝经后乳腺癌患者的研究中,口服给药灰树花提取物显示具有免疫调节作用。
香菇(shiitake mushroom)(Lentinula edodes)为东亚当地的食用菌。香菇含有真菌化学成分(mycochemicals),据推测其具有抗病毒、抗菌、抗炎、抗高血压和抗癌作用。这被认为主要是葡聚糖α和β葡聚糖二者的结果。一些香菇提取物具有含量超过40%的α葡聚糖。另外,香菇多糖(1,3β-D-葡聚糖),是一种自香菇分离的多糖,已被深入研究并被认为在香菇的有益效果中起作用。已显示其在结肠癌细胞中有抗癌作用,这可能由于其具有抑制细胞色素P4501A酶的能力,细胞色素P4501A酶已知用于将前致癌物代谢为活性形式。Lentin这种蛋白质组分具有强抗真菌性质并被发现抑制白血病细胞的增殖和抑制人类免疫缺陷病毒-1逆转录酶的活性。
灵芝(reishi mushroom)(Ganoderma lucidum),也被称为灵芝(lingzkimushrooms),是发现于东亚的食用菌。灵芝被认为具有抗肿瘤、抗癌、免疫调节以及免疫治疗作用。灵芝含有一些被认为是有助于其活性的组分,包括葡聚糖如β-葡聚糖、角黄素、甾醇、香豆素、灵芝酸以及甘露醇。
面包酵母(baker’s yeast)(酿酒酵母(Saccaromyces cerevisiae))可作为葡聚糖特别是β-葡聚糖的来源。面包酵母的活性组分可通过多种方式提取,如Bacon et al.Biochem J,1969,114(3):557-567;美国专利第7,803,605号;美国专利第5,702,719号;以及美国专利第8,323,644号中描述的方法,上述每篇文献以其全部内容通过引用并入本文。
葡聚糖在以下参考文献中有描述,这些参考文献中的每篇文献以其全部内容通过引用并入本文:Vetvicka et al.Endocr Metab Immun Disord DrugTargets,2009,9(1):67-75;以及Vetvicka et al.J Med Food,2008:11(4):615-622.
Zhang等(Proc.Natl.Acad.Sci.,(1994),Vol.91,pp.3147-3150)讨论在Sprague-Dawley大鼠中测定莱菔硫烷和结构上相关的合成降冰片基异硫氰酸酯(norbornyl isiothiocyanates)的抗癌活性的研究。研究确定了给予莱菔硫烷有效地阻止乳腺肿瘤的形成。
Cornblatt等(Carcinogenesis,(2007),Vol.38(7):pp.1485-1490)讨论在Sprague-Dawley大鼠中测定莱菔硫烷在乳腺化学预防中的作用的研究。研究确定了口服给药任一莱菔硫烷导致乳腺上皮组织中NAD(P)H:醌氧化还原酶(NQO1)酶活性增加3倍和血红素加氧酶-1(HO-1)酶的免疫染色升高4倍。
Munday等(Cancer Res,(2008),Vol.68(5):pp.1593-1600)讨论西兰花芽的冻干水提取物对大鼠膀胱癌发展的作用的研究。研究发现给药西兰花芽提取物导致显著诱导膀胱中谷胱甘肽S-转移酶和NAD(P)H:醌氧化还原酶1,这些酶是对氧化剂和致癌物有保护活性的酶。
Fang等(J Altern Complem Med,(2006),Vol.12(2):pp.125-132)讨论测定香菇乙酸乙酯萃取物对人乳腺癌细胞系(MDA-MB-453和MCF-7)、人良性乳腺上皮细胞系(MCF-10F)、以及两种骨髓瘤细胞系(RPMI08226和IM-9)的抗增殖作用的研究。研究发现香菇中的组分抑制肿瘤细胞的生长可能因为诱导细胞凋亡。
Kim等(J Med Food,(2007),Vol.10(1):pp.25-31)公开调查由香菇培养的米糠外生物聚合物(exo-biopolymer)的激活自然杀伤(NK)细胞作用和抗肿瘤作用的研究。研究发现外生物聚合物可通过激活自然杀伤细胞有效地预防和/或治疗癌症。
Louie等(BJUI,(2009),Vol.153(9):pp.1215-1221)讨论α-干扰素和生物活性提取物灰树花D-萃取物(PDF)的组合在体外对α-干扰素在膀胱癌T24细胞中的抗癌活性的协同效应。
Masuda等(Biol.Pharm.Bull.(2008),Vol.31(6):pp.1 104-1 108)讨论评估肺转移鼠模型中灰树花的萃取物的抗转移活性的研究。研究发现该萃取物抑制肿瘤转移是通过激活自然杀伤细胞和抗原呈递细胞(APC)并抑制粘附分子如ICAM-1,导致抑制肿瘤细胞粘附于血管内皮细胞。
欧洲专利申请第2 213 280号公开包含葡糖异硫氰酸酯如硫代葡萄糖苷以及黑芥子硫苷酸酶的制剂,其中所述制剂被装入胶囊或包衣。
本文引用的所有参考文献以其全部内容通过引用并入本文。
发明概述
本发明提供一种组合物,该组合物包含:(i)莱菔硫烷前体,优选硫代葡萄糖苷;(ii)能够将莱菔硫烷前体转化为莱菔硫烷的酶,优选葡糖苷酶,更优选硫葡糖苷酶,最优选黑芥子硫苷酸酶;(iii)酶增强剂,优选抗坏血酸;和(iv)蕈类(优选灰树花、香菇或灵芝)提取物或粉末。本发明还提供一种治疗、预防受试者的癌症,特别是乳腺癌、前列腺癌、结肠癌、肺癌以及膀胱癌,减少所述癌症的发生,减少与所述癌症相关的症状,和/或减少所述癌症的二次复发的方法,所述方法包括给予受试者:(i)莱菔硫烷前体,(ii)能够将莱菔硫烷前体转化为莱菔硫烷的酶,(iii)酶增强剂,和(iv)蕈类(优选灰树花、香菇或灵芝)提取物或粉末。本发明还提供一种增加受试者的NAD(P)H:醌氧化还原酶1(NQO-1)的水平或基因表达的方法,该方法包括给予受试者:(i)莱菔硫烷前体,(ii)能够将莱菔硫烷前体转化为莱菔硫烷的酶,(iii)酶增强剂,和(iv)蕈类(优选灰树花、香菇,或灵芝)提取物或粉末。本发明还提供一种治疗、预防与升高的醌雌激素水平相关的疾病或病症,减少所述疾病或病症的发生,减少与所述疾病或病症相关的症状,和/或减少所述疾病或病症的二次复发的方法,所述方法包括给予受试者:(i)莱菔硫烷前体,(ii)能够将莱菔硫烷前体转化为莱菔硫烷的酶,(iii)酶增强剂,和(iv)蕈类(优选灰树花、香菇或灵芝)提取物或粉末。
本发明提供一种组合物,所述组合物包含:(i)莱菔硫烷或其衍生物,和(ii)蕈类(优选灰树花、香菇或灵芝)提取物或粉末。本发明还提供一种治疗、预防受试者的癌症,特别是乳腺癌、前列腺癌、结肠癌、肺癌以及膀胱癌;减少所述癌症的发生;减少与所述癌症相关的症状,和/或减少所述癌症的二次复发的方法,所述方法包括给予受试者:(i)莱菔硫烷或其衍生物,和(ii)蕈类(优选灰树花、香菇或灵芝)提取物或粉末。本发明还提供一种增加受试者的NAD(P)H:醌氧化还原酶1(NQO-1)的水平或基因表达的方法,所述方法包括给予受试者:(i)莱菔硫烷或其衍生物,和(ii)蕈类(优选灰树花、香菇或灵芝)提取物或粉末。本发明还提供一种治疗、预防与升高的醌雌激素水平相关的疾病或病症;减少所述疾病或病症的发生;减少与所述疾病或病症相关的症状;和/或减少所述疾病或病症的二次复发的方法,所述方法包括给予受试者:(i)莱菔硫烷或其衍生物,和(ii)蕈类(优选灰树花、香菇或灵芝)提取物或粉末。
本发明提供一种组合物,所述组合物包含:(i)西兰花提取物或粉末,和(ii)蕈类(优选灰树花、香菇或灵芝)提取物或粉末。本发明还提供一种治疗、预防受试者的癌症,特别是乳腺癌、前列腺癌、结肠癌、肺癌以及膀胱癌;减少所述癌症的发生;减少与所述癌症相关的症状;和/或减少所述癌症的二次复发的方法,所述方法包括给予受试者:(i)西兰花提取物或粉末,和(ii)蕈类(优选灰树花、香菇或灵芝)提取物或粉末。本发明还提供一种增加受试者的NAD(P)H:醌氧化还原酶1(NQO-1)的水平或基因表达的方法,所述方法包括给予受试者:(i)西兰花提取物或粉末,和(ii)蕈类(优选灰树花、香菇或灵芝)提取物或粉末。本发明还提供一种治疗、预防与升高的醌雌激素水平相关的疾病或病症;减少所述疾病或病症的发生;减少与所述疾病或病症相关的症状;和/或减少所述疾病或病症的二次复发的方法,所述方法包括给予受试者:(i)西兰花提取物或粉末,和(ii)蕈类(优选灰树花、香菇或灵芝)提取物或粉末。
附图说明
图1显示硫代葡萄糖苷在38℃、无抗坏血酸的情况下的转化,如实施例4中所述。
图2显示在38℃下在约10分钟内的转化作为抗坏血酸浓度的函数,如实施例4中所述。
图3显示在38℃和1mM抗坏血酸的情况下在30分钟内到莱菔硫烷的转化,如实施例4中所述。
图4显示在模拟肠液中硫代葡萄糖苷到莱菔硫烷的转化,如实施例5中所述。
图5显示实施例6中所述的实验的结果。
图6显示实施例7中所述的实验的结果。
发明详述
本发明涉及莱菔硫烷前体、能够将莱菔硫烷前体转化为莱菔硫烷的酶、酶增强剂、以及蕈类(如灰树花、香菇或灵芝)提取物或粉末的组合。本发明还涉及莱菔硫烷或其衍生物和蕈类(如灰树花、香菇或灵芝)提取物或粉末的组合。本发明还涉及西兰花提取物或粉末和灰树花、香菇或灵芝提取物或粉末的组合。本发明还涉及蕈类提取物或粉末,与以下物质中的一种或多种的混合物的用途:莱菔硫烷前体、莱菔硫烷或其衍生物、以及西兰花提取物。本发明提供涉及这些组合的组合物。
本发明还提供包括给予这些组合的方法。在一些实施方案中,可给予组合用于治疗、预防受试者的癌症,特别是乳腺癌、前列腺癌、结肠癌、肺癌以及膀胱癌;减少所述癌症的发生;减少与所述癌症相关的症状;和/或减少所述癌症的二次复发,包括给予所述受试者。在一些实施方案中,可给予组合用于增加受试者的NAD(P)H:醌氧化还原酶1(NQO-1)的水平或基因表达。在一些实施方案中,可给予组合用于治疗、预防与升高的醌雌激素水平相关的疾病或病症,减少所述疾病或病症的发生,减少与所述疾病或病症相关的症状,和/或减少所述疾病或病症的二次复发。
莱菔硫烷也被称为1-异硫氰酸根合-4-甲基亚磺酰基丁烷。莱菔硫烷的衍生物包括但不限于莱菔硫烷的次硫酸硫代氨基甲酸酯(sulfoxythiocarbamate)类似物、6-甲基亚磺酰基己基异硫氰酸酯(6-HITC),以及包含在异硫氰酸根和亚砜基团之间具有不同侧链和/或不同长度的间隔单元(spacer)的莱菔硫烷结构的化合物。莱菔硫烷的衍生物的实例包括以下参考文献中所述的那些:Hu et al.,Eur J Med Chem,2013,64:529-539;Ahn et al.,Proc Natl Acad Sci USA,2010,107(21):9590-9595;和Morimistu et al.,J.Biol.Chem.2002,277:3456-3463,和Baird et al.,Arch Toxicol,2011,85(4):241-272,这些参考文献中的每一篇都以其全部内容通过引用并入本文。
在一些实施方案中,组合物包含如下量的莱菔硫烷或其衍生物,优选莱菔硫烷:约1μg至约10g,优选约3μg至约5g,优选约5μg至约1000mg,优选约7μg至约750mg,更优选约10μg至约500mg,以及最优选约100μg至约100mg。在一些实施方案中,适合人用的组合物包含约1mg至约20mg。
在一些实施方案中,本发明的方法包括给予受试者如下量的莱菔硫烷或其衍生物,优选莱菔硫烷:约1μg至约10g,优选约3μg至约5g,优选约5μg至约1000mg,优选约7μg至约750mg,更优选约10μg至约500mg,以及最优选约100μg至约100mg。在其中受试者为人的一些实施方案中,方法包括给予约1mg至约20mg。在一些实施方案中,本发明的方法包括以如下量给予受试者莱菔硫烷或其衍生物,优选莱菔硫烷:约0.01μg/kg至约0.2g/kg,优选约0.05μg/kg至约0.07g/kg,更优选约0.07μg/kg至约15mg/kg,更优选约0.1μg/kg至约11mg/kg,以及最优选约0.2μg/kg至约7mg/kg。在其中受试者为人的一些实施方案中,方法包括给予约2μg/kg至约2mg/kg,更优选约0.01mg/kg至约0.3mg/kg。上述量可指每次给予剂量或总日剂量。总日剂量指在二十四小时周期内给予受试者化合物或成分的总量。
在一些实施方案中,方法包括给予多于一种的莱菔硫烷或其衍生物。在一些实施方案中,组合物包含多于一种的莱菔硫烷或其衍生物。例如,方法或组合物可包含莱菔硫烷和其一种或多种衍生物,或两种或更多种衍生物。在其中方法或组合物包含多于一种的莱菔硫烷或其衍生物的一些实施方案中,上述量可指每种莱菔硫烷或其衍生物的量,或多于一种的莱菔硫烷或其衍生物的总量。
术语“莱菔硫烷前体(sulforaphane precursor)”指能用于产生莱菔硫烷的任何化合物、物质或材料。在优选的实施方案中,莱菔硫烷前体包括能优选通过酶被转化或代谢成莱菔硫烷的化合物。在一些优选的实施方案中,莱菔硫烷前体包括硫代葡萄糖苷。硫代葡萄糖苷是一种葡萄糖异硫氰酸酯,其也被称为4-甲基亚磺酰基丁基葡萄糖异硫氰酸酯(4-methylsulfinylbutylglucosinolate)和1-S-[(1E)-5-(甲基亚磺酰基)-N-(磺酸根氧基)戊亚胺基]-1-硫代-β-D-吡喃葡萄糖(1-S-[(1E)-5-(methylsulfinyl)-N-(sulfonatooxy)pentanimidoyl]-1-thio-β-D-glucopyranose)。
在一些实施方案中,组合物包含约1μg至约10g,优选约250μg至约5g,更优选约500μg至约2000mg,甚至更优选约1mg至约750mg,甚至更优选约1.5mg至约250mg,甚至更优选约2mg至约100mg,以及最优选约3mg至约75mg的莱菔硫烷前体,优选硫代葡萄糖苷。在一些实施方案中,适合人用的组合物包含约3.5mg至约50mg莱菔硫烷前体,优选硫代葡萄糖苷。
在一些实施方案中,方法包括以如下量给予受试者莱菔硫烷前体,优选硫代葡萄糖苷:约1μg至约10g,优选约250μg至约5g,更优选约500μg至约2000mg,甚至更优选约1mg至约750mg,甚至更优选约1.5mg至约250mg,甚至更优选约2mg至约100mg,最优选约3mg至约75mg。在其中受试者为人的一些实施方案中,方法包括给予约3.5mg至约50mg。在一些实施方案中,方法包括以如下量给予受试者莱菔硫烷前体:约1μg/kg至约1000mg/kg,优选约5μg/kg至约500mg/kg,更优选约7.5μg/kg至约100mg/kg,甚至更优选约10μg/kg至约25mg/kg,最优选约25μg/kg至约10mg/kg。在其中受试者为人的一些实施方案中,方法包括给予约50μg/kg至约800μg/kg。上述量可指每次给予剂量或总日剂量。
在一些实施方案中,方法包括给予多于一种的莱菔硫烷前体。在一些实施方案中,组合物包括多于的莱菔硫烷前体。在其中方法或组合物包含多于一种的莱菔硫烷前体的一些实施方案中,上述量可指每种莱菔硫烷前体的量,或莱菔硫烷前体的总量。
莱菔硫烷前体可被转化或代谢成莱菔硫烷。在一些实施方案中,莱菔硫烷前体通过酶被转化为莱菔硫烷。在一些实施方案中,能够将莱菔硫烷前体转化为莱菔硫烷的酶包括葡糖苷酶,优选硫葡糖苷酶,更优选黑芥子硫苷酸酶。黑芥子硫苷酸酶也被称为硫葡糖苷葡糖水解酶(thioglucosideglucohydrolase)。
在一些实施方案中,组合物包含如下量的酶:约1pg至约1μg,优选约50pg至约500ng,最优选约1ng至约150ng。在一些实施方案中,适合人用的组合物包含约5ng至约75ng的酶。
在一些实施方案中,方法包括以如下量给予酶,优选黑芥子硫苷酸酶:约1pg至约1μg,优选约50pg至约500ng,最优选约1ng至约150ng。在其中受试者为人的一些实施方案中,方法包括给予约5ng至约75ng的酶。在一些实施方案中,方法包括以如下量给予受试者酶:约0.02pg/kg至约0.02μg/kg,优选约0.7pg/kg至约7ng/kg,最优选约0.02ng/kg至约2ng/kg。在其中受试者为人的一些优选的实施方案中,方法包括给予约0.1ng/kg至约1ng/kg。上述量可指每次给药剂量或总日剂量。
在一些实施方案中,方法包括给予多于一种的能够将莱菔硫烷前体转化为莱菔硫烷的酶。在一些实施方案中,组合物包含多于一种的能够将莱菔硫烷前体转化为莱菔硫烷的酶。在其中方法或组合物包含多于一种酶的一些实施方案中,上述量可指每种酶的量,或酶的总量。
本发明还提供西兰花提取物和/或粉末的使用,所述西兰花提取物和/或粉末包括但不限于西兰花种子和芽提取物和粉末。本发明提供给予西兰花提取物和/或粉末以及包含西兰花提取物和/或粉末的组合物的方法。在一些实施方案中,西兰花提取物或粉末被标准化为含有约1%至约75%w/w,更优选约2.5%至约50%,甚至更优选约5%至约25%,最优选约10%至约20%的莱菔硫烷前体,优选硫代葡萄糖苷。西兰花提取物和粉末的实例包括但不限于美国专利第5,411,986号;第5,725,895号;第5,968,505号;第5,968,567号;第6,177,122号;第6,242,018号;第6,521,818号;第7,303,770号以及第8,124,135号中所述的那些,其中每篇专利以其全部内容通过引用并入本文。西兰花粉末可例如通过对西兰花优选西兰花芽进行空气干燥、冻干、滚筒干燥、喷雾干燥、热干燥和/或部分真空干燥来获得。在一些实施方案中,组合物和方法包括使用约1μg至约10g,更优选约250μg至约5g,甚至更优选约500μg至约1g,优选约600μg至约500mg,更优选约750μg至约400mg,最优选约1mg至约300mg的西兰花提取物。在一些实施方案中,西兰花提取物或粉末以一定量存在于组合物中或给予受试者,所述量足以提供上述量的莱菔硫烷前体或莱菔硫烷。在一些实施方案中,组合物可进一步包含酶增强剂,优选抗坏血酸。在一些实施方案中,方法可进一步包括给予酶增强剂,优选抗坏血酸。
莱菔硫烷或其衍生物、莱菔硫烷前体、和/或能够将莱菔硫烷前体转化为莱菔硫烷的酶可从任何来源获得,包括但不限于来自十字花科的一种或多种植物。十字花科植物的实例包括但不限于以下:西兰花、球芽甘蓝、菜花、卷心菜、山葵(horseradish)、欧防风(parsnip)、萝卜、山萮菜(wasabi)、水田芥以及白芥菜。在一些优选的实施方案中,莱菔硫烷前体(优选硫代葡萄糖苷)和酶(优选黑芥子硫苷酸酶)从西兰花、西兰花芽或西兰花种子中获得。莱菔硫烷前体和酶可从相同或不同的来源获得。在一些实施方案中,莱菔硫烷前体和酶可从这些植物的提取物或粉末(优选西兰花种子或芽提取物或粉末)中获得。
本发明提供酶增强剂的使用。酶增强剂可用于增强能够将莱菔硫烷前体转化为莱菔硫烷的酶的活性。在一些实施方案中,酶增强剂包括酶辅助因子,优选抗坏血酸。抗坏血酸也被称为抗坏血酸盐或维生素C,能增强黑芥子硫苷酸酶的活性。在一些实施方案中,在没有酶增强剂如抗坏血酸的情况下,转化为莱菔硫烷的反应可能太慢而难以在需要峰值吸收的位置发生。酶增强剂可从天然来源中获得,或者其可通过合成产生。
在一些实施方案中,组合物可包含约1mg至约500mg,优选约1mg至约250mg,最优选约1mg至约125mg的酶增强剂。在一些实施方案中,适合人用的组合物包含约1mg至约50mg的酶增强剂。
在一些实施方案中,本发明的方法包括以如下量给予酶增强剂,优选抗坏血酸:约1mg至约500mg,优选1mg至约250mg,最优选约1mg至约125mg。在其中受试者为人的一些实施方案中,方法包括给予约1mg至约50mg。在一些实施方案中,本发明的方法包括以如下量给予酶增强剂,优选抗坏血酸:约0.01mg/kg至约3mg/kg,以及最优选约0.02mg/kg至约2mg/kg。在其中受试者为人的一些实施方案中,方法包括给予约0.02mg/kg至约0.7mg/kg的酶增强剂。上述量可指每次给药剂量或总日剂量。
在一些实施方案中,方法包括给予多于一种的酶增强剂。在一些实施方案中,组合物包含多于一种的酶增强剂。在其中方法或组合物包含多于一种的酶增强剂的一些实施方案中,上述量可指每种酶增强剂的量,或酶增强剂的总量。
本发明提供蕈类提取物或粉末的使用。在一些实施方案中,蕈类可包括“药用蕈类”,包括但不限于灰树花、香菇、灵芝、褐菇、杏仁菇、栗菇、木耳、云耳、牛肝菌、墨汁鬼伞、yarta gunbu,金针菇、占地菇、虎奶菌、羊肚菌、竹菇、黄金菇、粉红平菇、杏鲍菇、平菇、菜花、银耳、金耳、松茸、墨西哥松露、以及草菇。
在优选的实施方案中,蕈类包括灰树花、香菇、灵芝,和/或这些中的一种或多种的混合物。
灰树花属于Grifola frondosa种类。灰树花可含有许多具有生物活性的成分。在灰树花中发现的组分的实例包括但不限于:葡聚糖(如α-葡聚糖和β-葡聚糖);脂类(如十八烷酸和十八碳二烯酸);磷脂类(如磷脂酰乙醇胺、磷脂酰胆碱、磷脂酰肌醇、磷脂酰丝氨酸和磷脂酸)。
香菇属于Lentinula edodes种类。香菇可含有许多具有生物活性的成分。在香菇中发现的组分实例包括,但不限于,葡聚糖(如α-葡聚糖和β-葡聚糖),蛋白质(如lentin);脂类(如亚油酸);以及木质素。
灵芝属于Ganoderma lucidum种类。灵芝可含有许多具有生物活性的成分。在灵芝中发现的组分的实例包括但不限于:葡聚糖(如α-葡聚糖和β-葡聚糖)、角黄素、甾醇、香豆素、灵芝酸以及甘露醇。
在一些优选的实施方案中,蕈类提取物或粉末包含一种或多种葡聚糖。葡聚糖是由糖苷键连接的D-葡萄糖单体的多糖,并可分为α或β型。在一些实施方案中,葡聚糖包含一种或多种α-葡聚糖和/或β-葡聚糖。α-葡聚糖包括但不限于:1,4-α-葡聚糖和1,6-α-葡聚糖,而β-葡聚糖包括但不限于:1,3-β-葡聚糖、1,4-β-葡聚糖以及1,6-β-葡聚糖。葡聚糖可以多种聚合构型表示。在优选的实施方案中,灰树花提取物或粉末包含1,3-β-葡聚糖和/或1,6-β-葡聚糖。在优选的实施方案中,香菇提取物或粉末包含1,4-α-葡聚糖。在优选的实施方案中,灵芝提取物或粉末包含1,3-β-葡聚糖和/或1,6-β-葡聚糖。在一些实施方案中,本发明的组合物和方法可包含使用纯化形式的葡聚糖或通过合成产生的葡聚糖,而不使用蕈类提取物或粉末。
在一些实施方案中,可使用灰树花提取物或粉末。在一些实施方案中,灰树花提取物或粉末被标准化为含有约1%至约75%,更优选约5%至约50%,甚至更优选约10%至约30%,最优选约15%至约20%的一种或多种葡聚糖,优选β-葡聚糖,更优选1,3-β葡聚糖和/或1,6-β-葡聚糖。灰树花提取物和粉末的实例包括但不限于在美国专利第5,854,404号;WO2007142130,EP 0893449;WO2009063885;WO2006107208;WO2007024496;以及WO2001054673中所述的那些,其中的每一篇均以其全部内容通过引用并入本文。灰树花粉末可例如通过对灰树花进行空气干燥、冻干、滚筒干燥、喷雾干燥、热干燥和/或部分真空干燥来获得。在一些实施方案中,组合物包含约250μg至约100mg,优选约500μg至约75mg,最优选约750μg至约50mg。在一些实施方案中,适合人的组合物包含约1mg至约20mg的灰树花提取物。在一些实施方案中,方法包括给予约250μg至约100mg,优选约500μg至约75mg,最优选约750μg至约50mg。在其中受试者为人的一些实施方案中,方法包括给予约1mg至约20mg的灰树花提取物。上述量可指每次给予剂量或总日剂量。
在一些实施方案中,可使用香菇提取物或粉末。在一些实施方案中,香菇提取物或粉末被标准化为含有约1%至约75%,优选约10%至约60%,甚至更优选约25%至约50%,最优选约30%至约40%的一种或多种葡聚糖,优选α-葡聚糖,更优选1,4-α-葡聚糖。香菇提取物的实例包括但不限于在美国专利第5,780,097号;美国专利第6,582,723号;WO2005107496,WO2007024496,以及WO2000033069中所述的那些,其中的每一篇以其全部内容通过引用并入本文。灰树花粉末可例如通过对灰树花进行空气干燥、冻干、滚筒干燥、喷雾干燥、热干燥和/或部分真空干燥来获得。在一些实施方案中,组合物包含约1mg至约1g,优选约10mg至约500mg,最优选约25mg至约300mg。在一些实施方案中,适合人的组合物包含约50mg至约250mg的香菇提取物或粉末。在一些实施方案中,方法包括给予约1mg至约1g,优选约10mg至约500mg,最优选约25mg至约300mg。在其中受试者为人的一些优选的实施方案中,方法包括给予受试者约50mg至约250mg的香菇提取物或粉末。上述量可指每次给予剂量或总日剂量。
在一些实施方案中,可使用灵芝提取物或粉末。在一些实施方案中,灵芝提取物包含约1%至约75%,更优选约5%至约50%,甚至更优选约10%至约30%,最优选约15%至约20%的一种或多种葡聚糖,优选β-葡聚糖,更优选1,3-β葡聚糖和/或1,6-β-葡聚糖。灰树花粉末可例如通过对灰树花进行空气干燥、冻干、滚筒干燥、喷雾干燥、热干燥和/或部分真空干燥来获得。
在一些实施方案中,组合物和/或方法包括使用一种类型的蕈类提取物或粉末,如灰树花提取物或粉末、香菇提取物或粉末或灵芝提取物或粉末。在一些实施方案中,组合物和/或方法包括使用一种或多种类型的蕈类提取物或粉末的混合物。在一些实施方案中,组合物和/或方法包括使用以下物质中的一种或多种的混合物:灰树花提取物或粉末、香菇提取物或粉末、以及灵芝提取物或粉末。组合物和方法可包括使用一种提取物或粉末,或提取物和粉末的混合物。
本发明还提供使用替代蕈类提取物或粉末的任何富含葡聚糖的组分,或者除蕈类提取物或粉末外还使用任何富含葡聚糖的组分。富含葡聚糖的组分的实例为面包酵母。在一些实施方案中,可使用酵母制剂。在一些实施方案中,酵母制剂包含约0.1%至约50%,优选约0.5%至约25%,最优选约0.5%至约10%的一种或多种葡聚糖。酵母制剂的实例包括在美国专利第5,223,491号和美国专利第5,576,015号中讨论的那些,其中的每一篇以其全部内容通过引用并入本文。
本发明的方法可进一步包括给予一种或多种其它组分。本发明的组合物可进一步包含一种或多种其它组分。该其它组分可包括活性药物成分、营养补充剂以及营养提取物。该其它组分的实例包括但不限于:熊果酸(ursolicacid)、槲皮素或其衍生物、氨基糖如葡萄糖胺(glucosamine)、糖胺聚糖(glycosaminoglycan)如软骨素(chondroitin)、鳄梨/大豆不皂化物(avocado/soybean unsaponifiables)、维生素如维生素K2、咖啡果(coffee fruit)、镁、熊果酸、原花青素(proanthocyanidins)、α-和β-葡聚糖、姜黄素(curcumin)、植物甾醇(phytosterols)、植物甾烷醇(phytostanols)以及S-腺苷甲硫氨酸(SAMe)。这些其它组分可存在于水飞蓟(Silybum marianum)提取物(水飞蓟素)、蔓越莓(Vaccinium macrocarpon)提取物(原花青素、槲皮素以及熊果酸)、姜黄(Curcuma longa)。
在一些实施方案中,β-葡聚糖与莱菔硫烷或其衍生物的比例(β-葡聚糖:莱菔硫烷或其衍生物)为约50:1至约1:50,优选约25:1至约1:25,更优选约10:1至约1:20,更优选约5:1至约1:10,甚至更优选约1:1至约1:8,最优选约1:3至约1:5。在一些实施方案中,α-葡聚糖与莱菔硫烷或其衍生物的比例(α-葡聚糖:莱菔硫烷或其衍生物)为约1:50至约50:1,优选约1:10至约25:1,更优选约1:5至约20:1,更优选约1:1至约15:1,甚至更优选约2:1至约10:1,最优选约3:1至约8:1。在一些实施方案中,β-葡聚糖与莱菔硫烷前体的比例(β-葡聚糖:莱菔硫烷前体)为约50:1至约1:50,优选约30:1至约1:35,更优选约20:1至约1:25,更优选约10:1至约1:20,甚至更优选约5:1至约1:15,最优选约1:1至约1:10。在一些实施方案中,α-葡聚糖与前体的比例(α-葡聚糖:前体)为约1:50至约100:1,优选约1:25至约75:1,更优选约1:10至约50:1,更优选约1:5至约40:1,甚至更优选约1:1至约30:1,最优选约2:1至约20:1。
在一些实施方案中,组合物包括单位剂型,包括但不限于适于口服、直肠、静脉内、皮下、肌内、经皮、经粘膜,以及局部给药的药物剂型。在一些优选的实施方案中,组合物包括口服给药剂型或直肠给药剂型。口服给药剂型的实例包括但不限于片剂、胶囊剂、能分散于饮料中的粉剂、液体剂如溶液、混悬液或乳剂、软胶囊/咀嚼胶囊、咀嚼棒,或本领域已知的其它便利剂型。在优选的实施方案中,组合物包括片剂、胶囊剂,或软咀嚼处理形式。口服给药剂型可被配制成速释、缓释或延释。
在一些实施方案中,在一种剂型中提供至少莱菔硫烷前体、酶和酶增强剂,所述剂型允许在pH为至少4(优选为至少5)的胃肠道区域(如小肠,优选十二指肠)中释放。在一些实施方案中,在一种剂型中提供至少莱菔硫烷或其衍生物和/或西兰花提取物或粉末,所述剂型允许在pH为至少4(优选为至少5)的胃肠道区域(如小肠,优选十二指肠)中释放。在一些实施方案中,蕈类提取物或粉末和/或任何任选的其它组分也在pH为至少4(优选为至少5)的胃肠道区域(如小肠,优选十二指肠)中释放。小肠包括十二指肠、空肠和回肠。
在一些实施方案中,这些组分(即,莱菔硫烷前体、酶、酶增强剂、莱菔硫烷或其衍生物、西兰花提取物或粉末、蕈类提取物或粉末,和/或其它组分)中的每一种同时或伴随释放(即,互相在短时间内)。这相对于被配制成在pH低于4的胃肠道区域如胃中释放硫代葡萄糖苷的含硫代葡萄糖苷的组合物具有益处。在低pH环境如这样中,酸性环境可将莱菔硫烷前体的转化转移为形成其它生理上无活性的终产物,如莱菔硫烷腈和环硫腈(epithionitrile)。
在一些实施方案中,组合物可包括口服给药组合物,该口服给药组合物包括肠溶衣剂型或抵抗在pH低于4的胃肠道区域如胃中降解的任何剂型。例如,口服给药组合物可包括含有肠溶衣的片剂或胶囊剂。肠溶衣可包含的材料包括但不限于邻苯二甲酸乙酸纤维素、邻苯二甲酸羟丙基甲基纤维素、聚乙酸乙烯邻苯二甲酸酯、甲基丙烯酸共聚物、甲基丙烯酸:丙烯酸酯共聚物、乙酸羟丙基甲基纤维素琥珀酸酯、偏苯三酸羟丙基甲基纤维素、虫胶、偏苯三酸乙酸纤维素、羧甲基乙基纤维素,及它们的混合物。肠溶衣可包含本领域已知的任何合适的肠溶性聚合物。在一些实施方案中,组合物中的一种或多种组分可被包埋在肠溶性聚合物基质中。在一些实施方案中,口服给药组合物包括在胃酸中缓慢溶解并进入小肠的胶囊剂,如以上市的DRCAPSTM耐酸性胶囊或其它耐酸性胶囊。
在最优选的剂型中,口服给药组合物被包衣包裹,除非周围介质的pH为至少4,更优选为至少5,否则所述包衣不溶解。可选地,可使用与pH相反,以调节的速率按时间来控制释放的包衣,从而使组分不释放,直到胃肠道的pH升至至少4,更优选升至至少5。因此,时间释放制剂(time-releaseformulation)可用于防止莱菔硫烷前体、能够将莱菔硫烷前体转化为莱菔硫烷的酶和酶增强剂,或莱菔硫烷在胃中出现。可使用标准包衣技术将包衣层施加于口服给药组合物。肠溶衣材料可溶解或分散于有机溶剂或含水溶剂中。肠溶衣溶解的pH可通过所选的聚合物或聚合物的组合和/或侧基的比例来控制。例如,聚合物膜的溶出性质可通过游离羧基与酯基的比例改变。肠溶衣层还含有药学上可接受的增塑剂如柠檬酸三乙酯、邻苯二甲酸二丁酯、三乙酸甘油酯、聚乙二醇、聚山梨酸酯或其它增塑剂。还可包括添加剂如分散剂、着色剂、抗粘附剂和防沫剂。
组合物可含有一种或多种非活性药物成分(通常也被称为“赋形剂”)。非活性成分例如用于溶解、混悬、增稠、稀释、乳化、稳定、防腐、保护、着色、矫味、以及改变活性成分形成适用和有效的制剂,所述制剂是安全、方便,以及其它使用上可接受的。赋形剂优选药学上可接受的赋形剂。药学上可接受的赋形剂的种类的实例包括润滑剂、缓冲剂、稳定剂、发泡剂、色素、着色剂、矫味剂、填充剂、膨胀剂、芳香剂、释放调节剂、佐剂、增塑剂、流动加速剂、脱模剂、多元醇、成粒剂、稀释剂、粘合剂、缓冲液、吸附剂、助流剂、胶粘剂、抗粘剂、酸化剂、软化剂、树脂、缓和剂、溶剂、表面活性剂、乳化剂、弹性剂及它们的混合物。
在一些实施方案中,(i)莱菔硫烷前体,优选硫代葡萄糖苷,(ii)能够将莱菔硫烷前体转化为莱菔硫烷的酶,优选葡糖苷酶,更优选硫葡糖苷酶,最优选黑芥子硫苷酸酶,(iii)酶增强剂,优选酶辅助因子,更优选抗坏血酸,和(iv)蕈类提取物或粉末(其含有葡聚糖)的组合展示出协同效应。在一些实施方案中,莱菔硫烷(或其衍生物)和蕈类提取物或粉末(其含有葡聚糖)的组合展示出协同效应。协同作用是指两种或多种组分的组合提供大于单独使用时产生的效应之和的结果的效应。在优选的实施方案中,协同效应大于累加效应。在一些实施方案中,莱菔硫烷前体、能够将莱菔硫烷前体转化为莱菔硫烷的酶、酶增强剂,以及灰树花、香菇或灵芝提取物或粉末的组合与以下相比具有统计学上显著的、更大的效应:(i)每种组分单用,(ii)单用莱菔硫烷前体和酶的组合;和/或(iii)单用莱菔硫烷前体、酶以及酶增强剂的组合。
在优选的实施方案中,莱菔硫烷前体、酶、酶增强剂以及蕈类提取物或粉末(其含有葡聚糖)的组合通过具有与单用莱菔硫烷前体和单用蕈类提取物或粉末的累加效应相比为统计学上显著的和/或更大的效应,而展示出协同作用。在一些实施方案中,硫代葡萄糖苷、黑芥子硫苷酸酶、抗坏血酸,以及蕈类提取物或粉末的组合与单用硫代葡萄糖苷、黑芥子硫苷酸酶、抗坏血酸的组合相比;以及与单用葡聚糖相比,具有协同效应。
在一些实施方案中,莱菔硫烷(或其衍生物)和蕈类提取物或粉末的组合具有与以下的累加效应相比为统计学上显著和/或更大的效应:(i)单用莱菔硫烷(或其衍生物),和/或(ii)单用蕈类提取物或粉末。在一些实施方案中,莱菔硫烷和葡聚糖的组合与莱菔硫烷单用和葡聚糖单用相比有协同效应。
在一些实施方案中,西兰花提取物或粉末和蕈类提取物或粉末的组合具有与以下的累加效应相比为统计学上显著和/或更大的效应:(i)西兰花提取物或粉末单用,和/或(ii)蕈类提取物或粉末单用。在一些实施方案中,西兰花提取物或粉末和葡聚糖的组合与西兰花提取物或粉末单用和葡聚糖单用相比具有协同效应。
本发明提供使用方法,包括给予有需要的受试者的方法。在一些实施方案中,方法包括给予莱菔硫烷前体、能够将莱菔硫烷前体转化为莱菔硫烷的酶、酶增强剂以及蕈类提取物或粉末的组合。在一些实施方案中,方法包括给予莱菔硫烷或其衍生物和蕈类提取物或粉末的组合。在一些实施方案中,方法包括给予西兰花提取物或粉末和蕈类提取物或粉末的组合。
在一些实施方案中,方法涉及治疗、预防受试者的癌症,特别是乳腺癌、前列腺癌、结肠癌、肺癌、肝癌以及膀胱癌;减少所述癌症的发生;减少与所述癌症相关的症状;和/或减少所述癌症的二次复发。方法可用于减少或减慢对组织和器官如乳腺、前列腺、结肠、肺、肝以及膀胱的损伤。本发明提供治疗、预防与生殖系统(包括但不限于乳腺和前列腺)、结肠、肝、膀胱、肾、中枢神经系统、心血管系统、肺部系统、生殖泌尿系统、造血系统和关节相关的疾病或病症,减少与所述疾病或病症相关的症状,和/或减少所述疾病或病症的二次复发的方法。本发明还提供治疗、预防囊肿,如良性囊肿;减少与所述囊肿相关的症状,和/或减少所述囊肿的二次复发的方法。
在一些实施方案中,方法涉及增加受试者的NAD(P)H:醌氧化还原酶1(NQO-1)的水平或基因表达。方法还可用于治疗、预防受益于NQO-1的基因表达或水平增加的疾病或病症;减少与所述疾病或病症相关的症状;和/或减少所述疾病或病症的二次复发。这样的疾病或病症的实例包括但不限于癌症、骨髓增生异常综合征(myelodysplastic syndrome)、心血管疾病以及迟发性运动障碍(tardive dyskinesia)。
在一些实施方案中,方法涉及治疗、预防与升高的醌雌激素水平相关的疾病或病症,减少所述疾病或病症的发生,减少与所述疾病或病症相关的症状,和/或减少所述疾病或病症的二次复发。这样的疾病或病症的实例包括但不限于肿瘤、骨髓增生异常综合征、心血管疾病以及迟发性运动障碍。
在一些实施方案中,方法涉及对生物标记物提供有益的作用,和治疗、预防与这些生物标记物的异常水平相关的疾病或病症,减少所述疾病或病症的发生,减少与所述疾病或病症相关的症状。这样的生物标记物的实例包括但不限于NADPH依赖性酶、硫氧还蛋白(TXN)、硫氧还蛋白还原酶-1(Txnrd-1)、谷氨酸盐-半胱氨酸连接酶亚基(GCLC)、磺基转移酶1A1(SULT1A1)、血红素加氧酶-1(HMOX1)、谷胱甘肽过氧化物酶-3(GPx-3)、谷胱甘肽S-转移酶θ2(GSTT2)、微粒体谷胱甘肽S-转移酶1(MGST1)、醛氧化酶(AOX1)、醛酮还原酶1B8(Akr1b8)、含黄素单加氧酶2(FMO2)、Fc受体区域受体III(Fcgr3)、类胰蛋白酶β1(TPSB1)、肥大细胞蛋白酶-6(Mcpt6)、轴突蛋白-1-α(NRXN-1)、小眼畸形相关转录因子(MITF)、II型碘化甲腺原氨酸脱碘酶(DIO2)、血管生成素-14(Angpt14)、分化簇(CD36)、以及Ntel。与这些生物标记物的升高或异常水平相关的疾病或病症包括但不限于癌症、肺部和中枢神经系统结核(pulmonary and central nervous systemtuberculosis)、多发性硬化症(multiple sclerosis)、克罗恩病(Crohn's disease)、动脉粥样硬化(atherosclerosis)、骨关节炎(osteoarthritis)、哮喘(asthma)、中风(stroke)、肺气肿(emphysema)、糖尿病肾病(diabetic nephropathy)、慢性组织细胞性胎盘绒毛间隙炎(chronic histiocytic intervillositis of the placenta)、高血压(hypertension)、腹主动脉瘤(abdominal aortic aneurysm)、炎性肠病(inflammatory bowel disease)、慢性鼻窦炎(chronic rhinosinusitis)、冠状动脉病(coronary artery disease)、以及肾病(kidney disease)。
在一些实施方案中,方法包括给予有需要的受试者莱菔硫烷和含有葡聚糖的蕈类提取物或粉末的组合。在一些实施方案中,方法包括给予有需要的受试者西兰花提取物或粉末和含有葡聚糖的蕈类提取物或粉末的组合。在一些实施方案中,方法包括给予受试者硫代葡萄糖苷、黑芥子硫苷酸酶、抗坏血酸和含有葡聚糖的蕈类提取物或粉末的组合。在优选的实施方案中,组合物在本发明的方法中展示出协同效应。
在优选的实施方案中,组合的一种或多种组分(例如,莱菔硫烷前体、能够将莱菔硫烷前体转化为莱菔硫烷的酶、酶增强剂、蕈类提取物或粉末;或莱菔硫烷或其衍生物和蕈类提取物或粉末;或西兰花提取物或粉末和蕈类提取物或粉末)以一种组合物或剂型一起给药,或优选在其治疗作用重叠的周期内分开给药。在一些实施方案中,组合的组分可以两种或更多种口服给药组合物或剂型给药。例如,在一些实施方案中,莱菔硫烷前体、能够将莱菔硫烷前体转化为莱菔硫烷的酶、以及酶增强剂以一种口服给药剂型给药,而蕈类提取物或粉末以一种或多种单独的或额外的口服剂型给药。在优选的实施方案中,组合的组分以一种剂型给药。
在一些实施方案中,组合可以每日1至10次,优选每日1至5次,更优选每日1至3次,最优选每日1次的频率给药。
本申请中公开的剂量优选是指适合人的剂量。剂量计算可由本领域的技术人员通过评价体重、表面积、代谢速率以及物种差异来确定。
术语“受试者”是指任何动物,包括哺乳动物和鸟类。哺乳动物包括但不限于人、狗、猫、马、牛、骆驼、象、狮子、虎、熊、海豹以及兔。在优选的实施方案中,受试者包括不作为食物被消耗的哺乳动物,如人、猫和狗。
实施例
实施例1(制剂)
以下为本发明的示例性制剂:
制剂A
含硫代葡萄糖苷的西兰花种子提取物(约12%w/w),50mg至5g
含黑芥子硫苷酸酶的冻干西兰花芽粉末,25mg至500mg
抗坏血酸,1mg至50mg
含α葡聚糖的香菇提取物(约40%w/w),1mg至250mg。
制剂B
含硫代葡萄糖苷的西兰花种子提取物(约12%w/w),50mg至5g
含黑芥子硫苷酸酶的冻干西兰花芽粉末,25mg至500mg
抗坏血酸,1mg至50mg
含β葡聚糖的灰树花提取物(约20%w/w),1至100mg。
制剂C
一种口服给药组合物,包含:
西兰花种子提取物
西兰花芽提取物
灰树花提取物
抗坏血酸
羟丙基甲基纤维素
微晶纤维素
玉米淀粉
乙基纤维素
交联羧甲纤维素钠
羟基乙酸淀粉钠
交聚维酮
二氧化硅
海藻酸钠
中链甘油三酯
麦芽糖糊精
油酸
硬脂酸镁
硬脂酸
实施例2
开发一种疏水相互作用色谱(HILIC)方法,包含以下条件:
柱:Waters BEH酰胺,1.7μm粒径;2.1mm×100mm
流动相:20%10mM乙酸铵,pH 5.0;80%乙腈;
分离模式:等度
柱温:70℃
流速:0.7mL/min
以上条件允许分离五种典型的十字花科葡萄糖异硫氰酸酯,包括莱菔硫烷前体硫代葡萄糖苷。
实施例3
硫代葡萄糖苷的消耗作为抗坏血酸浓度的函数。
约250mg含有约12%(w/w)的硫代葡萄糖苷的西兰花种子提取物在0至600μmol/L范围内的不同浓度的抗坏血酸的存在下,通过固定浓度的源于西兰花芽的黑芥子硫苷酸酶进行水解。反应混合物恒温在38℃;60分钟内每15分钟取出等份样品,并用色谱法测定硫代葡萄糖苷的浓度。硫代葡萄糖苷消耗的速率被认为是其转化为莱菔硫烷的速率。硫代葡萄糖苷含量减少作为抗坏血酸浓度增加的函数的图形表示导致一系列线性图;线性回归线的斜率反映硫代葡萄糖苷消耗的速率,用μmol/min表示。很明显在浓度为600μmol/L的抗坏血酸的存在下,反应速率相对于在不存在抗坏血酸调节作用下进行的反应速率增加13倍。
实施例4
硫代葡萄糖苷等摩尔转化为莱菔硫烷。
进行两部分实验以进一步说明抗坏血酸在调节黑芥子硫苷酸酶活性中的作用。在20mM Tris-缓冲盐水,pH 7.5中制备所有溶液,所述缓冲盐水以前被确定为对于黑芥子硫苷酸酶活性是最佳的;每一样品管有精确称重的100mg冻干的西兰花粉末作为黑芥子硫苷酸酶的来源。实验在38℃进行2小时,每增加30分钟移出等份样品,并且硫代葡萄糖苷和莱菔硫烷的含量均由HPLC评估。使用强酸性“终止”溶液以立即抑制移出的等份样品中的黑芥子硫苷酸酶的进一步活性。对照样品不含抗坏血酸,并且酶转化在无辅助因子的辅助下进行。
部分1.在固定浓度的抗坏血酸(1mmol/L)的存在下,加入在250mg至500mg范围内的增加量的西兰花种子提取物(约12%硫代葡萄糖苷,w/w)。
部分2.在保持西兰花种子提取物的量固定在250mg时,抗坏血酸的浓度从0.4mmol/L变化至3.8mmol/L。
下表示出以μmol表示的硫代葡萄糖苷和莱菔硫烷。很明显在最初30分钟内,在几乎所有的反应混合物中,硫代葡萄糖苷到莱菔硫烷的转化是完全的。但是,仔细检查在无抗坏血酸的刺激作用的对照样品中发生的酶转化,显示硫代葡萄糖苷等摩尔转化为莱菔硫烷,即,消耗的硫代葡萄糖苷的量导致产生等摩尔量的莱菔硫烷。
在实验的部分2中,评估了增加的抗坏血酸浓度对黑芥子硫苷酸酶活性的调节作用。对于约2mmol/L的抗坏血酸浓度,观察到对黑芥子硫苷酸酶促进的硫代葡萄糖苷到莱菔硫烷的转化观察到开始明显为线性的增加,随后呈现相当平稳的状态。
最后,在实验的部分1中对30分钟后莱菔硫烷产率的检查,显示在1mmol/L抗坏血酸的存在下,100mg冻干的西兰花芽粉末含有的固定量的黑芥子硫苷酸酶能够以可预测的线性方式产生至少200μmol莱菔硫烷。图1、图2、图3和图4展示出该研究的结果。
实施例5
在模拟肠液的存在下硫代葡萄糖苷到莱菔硫烷的转化。
使用模拟肠液(SIF)粉,一种商业供应的浓缩物,其在组成、pH和离子强度方面非常接近于人的肠内容物。实验使用USP溶出装置2(桨法),其中在六个溶出容器中分配500mL模拟肠液,以及150mg冻干的西兰花芽粉末作为黑芥子硫苷酸酶的来源。在容器1-4中,抗坏血酸的浓度从0.25变化至1.00mmol/L;在容器5中,除了1mmol/L抗坏血酸外,混悬3.125g胰酶(8xUSP);在容器6中,除了1mmol/L抗坏血酸和3.125g胰酶(8x USP)外,加入双倍量的冻干的西兰花芽粉末(300mg)。在容器达到38℃后,分别向每个容器中加入250mg富含硫代葡萄糖苷(12%,w/w)的西兰花种子提取物,并将得到的混悬液以75RPM搅拌2小时。每15分钟取出等份样品,并对莱菔硫烷进行含量测定。图4显示在较大的莱菔硫烷产率和较高的抗坏血酸浓度之间具有直接相关性,尤其是在实验的早期阶段。
实施例6
进行以下研究以测定莱菔硫烷和含有20%b-葡聚糖的灰树花提取物的组合对Nad(P)H:醌氧化还原酶1(NQO-1)的基因表达的作用。NQO-1编码能代谢雌激素醌的蛋白质,防止雌激素醌形成引起突变和最终致癌的DNA加合物。NQO-1表达的增加对于乳腺、结肠、肝、肺、皮肤和前列腺健康是有利的。
在研究中,将巨噬细胞系RAW 264.7用DMSO(溶媒对照)、莱菔硫烷(SFN)、含有20%β-葡聚糖的灰树花提取物(灰树花)、或莱菔硫烷和灰树花提取物的组合处理24小时。具体地,细胞用以下的一种进行处理:(i)DMSO(溶媒对照),(ii)0.5μΜ SFN,(iii)250μg/mL灰树花,(iv)500μg/mL灰树花,(v)750μg/mL灰树花,(vi)0.5μΜ SFN和250μg/mL灰树花,(vii)0.5μΜ SFN和500μg/mL灰树花,以及(viii)0.5μΜ SFN和750μg/mL灰树花。NQO-1基因表达的基因表达经由定量RT-PCR分析。图5中描绘的结果显示如下:
处理 | NQO-1基因表达的倍数增加 |
DMSO | 1.00 |
0.5μM SFN | 12.96 |
250μg/mL灰树花 | 1.34 |
0.5μM SFN+250μg/mL灰树花 | 55.97 |
500μg/mL灰树花 | 1.67 |
0.5μM SFN+500μg/mL灰树花 | 60.52 |
750μg/mL灰树花 | 2.31 |
0.5μM SFN+750μg/mL灰树花 | 59.47 |
结果证明莱菔硫烷和灰树花提取物的组合与每个组分单用相比具有协同效应。发现该效应大于单纯的累加。
实施例7
进行以下研究以测定莱菔硫烷和含有40%α葡聚糖的香菇提取物的组合对Nad(P)H:醌氧化还原酶1(NQO-1)的基因表达的作用。
在研究中,将巨噬细胞系RAW 264.7用DMSO(溶媒对照)、莱菔硫烷(SFN)、含有至少20%α-葡聚糖的香菇提取物(香菇)、或莱菔硫烷和香菇提取物的组合处理24小时。具体地,细胞用以下的一种进行处理:(i)DMSO(溶媒对照),(ii)0.5μΜ SFN,(iii)100μg/mL香菇,(iv)250μg/mL香菇,(v)500μg/mL香菇,(vi)0.5μΜ SFN和100μg/mL香菇,(vii)0.5μΜ SFN和250μg/mL香菇,以及(viii)0.5μΜ SFN和500μg/mL香菇。NQO-1基因表达的基因表达经由定量RT-PCR分析。图6中描绘的结果显示如下:
处理 | NQO-1基因表达的倍数增加 |
DMSO | 1.00 |
0.5μM SFN | 12.96 |
100μg/mL香菇 | 1.00 |
0.5μM SFN+100μg/mL香菇 | 14.58 |
250μg/mL香菇 | 1.27 |
0.5μM SFN+250μg/mL香菇 | 16.07 |
500μg/mL香菇 | 1.26 |
0.5μM SFN+500μg/mL香菇 | 15.20 |
结果证明莱菔硫烷和香菇提取物的组合与每个组分单用相比具有协同效应。发现该效应大于单纯的累加。
实施例8
受试者患有乳腺癌并具有包括乳腺组织损伤和乳房疼痛的症状。对她给予一片含有硫代葡萄糖苷、黑芥子硫苷酸酶、抗坏血酸和灰树花提取物的片剂。该片剂为在小肠释放内容物的肠溶衣制剂。每日给予该片剂一个月后,受试者经历替代性生物标记物包括NQO-1的调节,这与症状改善相关。
实施例9
受试者患有乳腺癌并具有包括乳腺组织损伤和乳房疼痛的症状。对她给予一片含有硫代葡萄糖苷、黑芥子硫苷酸酶、抗坏血酸和香菇提取物的片剂。该片剂为在小肠释放内容物的肠溶衣制剂。每日给予该片剂一个月后,受试者经历替代性生物标记物包括NQO-1的调节,这与症状改善相关。
Claims (21)
1.一种口服给药组合物,包含:
莱菔硫烷前体;
能够将所述莱菔硫烷前体转化为莱菔硫烷的酶;
酶增强剂;以及
蕈类提取物或粉末。
2.权利要求1所述的口服给药组合物,其中所述莱菔硫烷前体包括硫代葡萄糖苷。
3.权利要求1所述的口服给药组合物,其中所述能够将所述莱菔硫烷前体转化为莱菔硫烷的酶包括黑芥子硫苷酸酶。
4.权利要求1所述的口服给药组合物,其中所述酶增强剂包括抗坏血酸。
5.权利要求1所述的口服给药组合物,其中所述组合物包括肠溶衣剂型。
6.权利要求1所述的口服给药组合物,其中所述蕈类提取物或粉末包括灰树花提取物。
7.权利要求1所述的口服给药组合物,其中所述蕈类提取物或粉末包括香菇提取物。
8.权利要求1所述的口服给药组合物,其中所述蕈类提取物或粉末包括灰树花提取物和香菇提取物的混合物。
9.权利要求1所述的口服给药组合物,其中组合物进一步包含一种或多种其它组分,所述其它组分选自:槲皮素、氨基糖、糖胺聚糖、鳄梨/大豆不皂化物、维生素、咖啡果、镁、水飞蓟素、原花青素、熊果酸、姜黄素、植物甾醇、以及植物甾烷醇。
10.权利要求1所述的口服给药组合物,包含硫代葡萄糖苷、黑芥子硫苷酸酶、抗坏血酸、以及灰树花提取物。
11.权利要求1所述的口服给药组合物,包含硫代葡萄糖苷、黑芥子硫苷酸酶、抗坏血酸、以及香菇提取物。
12.权利要求1所述的口服给药组合物,包含硫代葡萄糖苷、黑芥子硫苷酸酶、抗坏血酸、灰树花提取物以及香菇提取物。
13.权利要求1所述的口服给药组合物,其中所述组合物包含西兰花提取物或粉末。
14.一种治疗、预防乳腺癌;减少乳腺癌的发生;减少与乳腺癌相关的症状;和减少乳腺癌的二次复发的方法,包括给予有需要的受试者莱菔硫烷前体;能够将莱菔硫烷前体转化为莱菔硫烷的酶;酶增强剂;以及蕈类提取物或粉末。
15.权利要求14所述的方法,其中所述莱菔硫烷前体包括硫代葡萄糖苷。
16.权利要求14所述的方法,其中所述能够将所述莱菔硫烷前体转化为莱菔硫烷的酶包括黑芥子硫苷酸酶。
17.权利要求14所述的方法,其中所述酶增强剂包括抗坏血酸。
18.权利要求14所述的方法,包括给予硫代葡萄糖苷、黑芥子硫苷酸酶、抗坏血酸、以及灰树花提取物。
19.权利要求14所述的方法,包括给予硫代葡萄糖苷、黑芥子硫苷酸酶、抗坏血酸、以及香菇提取物。
20.权利要求14所述的方法,包括给予硫代葡萄糖苷、黑芥子硫苷酸酶、抗坏血酸、灰树花提取物、以及香菇提取物。
21.权利要求14所述的方法,包括给予肠溶衣剂型。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201810409516.XA CN108355136B (zh) | 2012-07-05 | 2013-07-03 | 包含莱菔硫烷或莱菔硫烷前体和蕈类提取物或粉末的组合物 |
Applications Claiming Priority (15)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201261668396P | 2012-07-05 | 2012-07-05 | |
US201261668328P | 2012-07-05 | 2012-07-05 | |
US201261668364P | 2012-07-05 | 2012-07-05 | |
US201261668374P | 2012-07-05 | 2012-07-05 | |
US201261668386P | 2012-07-05 | 2012-07-05 | |
US201261668342P | 2012-07-05 | 2012-07-05 | |
US61/668,342 | 2012-07-05 | ||
US61/668,328 | 2012-07-05 | ||
US61/668,364 | 2012-07-05 | ||
US61/668,386 | 2012-07-05 | ||
US61/668,374 | 2012-07-05 | ||
US61/668,396 | 2012-07-05 | ||
US201361794417P | 2013-03-15 | 2013-03-15 | |
US61/794,417 | 2013-03-15 | ||
PCT/US2013/049248 WO2014008353A2 (en) | 2012-07-05 | 2013-07-03 | Compositions comprising sulforaphane or a sulforaphane precursor and a mushroom extract or powder |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201810409516.XA Division CN108355136B (zh) | 2012-07-05 | 2013-07-03 | 包含莱菔硫烷或莱菔硫烷前体和蕈类提取物或粉末的组合物 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN104427981A true CN104427981A (zh) | 2015-03-18 |
CN104427981B CN104427981B (zh) | 2018-05-25 |
Family
ID=49882601
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201810409516.XA Active CN108355136B (zh) | 2012-07-05 | 2013-07-03 | 包含莱菔硫烷或莱菔硫烷前体和蕈类提取物或粉末的组合物 |
CN201380035766.7A Active CN104427981B (zh) | 2012-07-05 | 2013-07-03 | 包含莱菔硫烷或莱菔硫烷前体和蕈类提取物或粉末的组合物 |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201810409516.XA Active CN108355136B (zh) | 2012-07-05 | 2013-07-03 | 包含莱菔硫烷或莱菔硫烷前体和蕈类提取物或粉末的组合物 |
Country Status (11)
Country | Link |
---|---|
US (14) | US20150174213A1 (zh) |
EP (5) | EP2849737B1 (zh) |
JP (10) | JP6436443B2 (zh) |
CN (2) | CN108355136B (zh) |
AU (8) | AU2013286713B2 (zh) |
CA (5) | CA2877356C (zh) |
ES (3) | ES2755757T3 (zh) |
PL (2) | PL2849736T3 (zh) |
RU (2) | RU2666953C2 (zh) |
TW (6) | TW201402130A (zh) |
WO (4) | WO2014008341A2 (zh) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN110946996A (zh) * | 2019-05-08 | 2020-04-03 | 深圳福山生物科技有限公司 | 包含萝卜硫苷的组合物及其用途 |
Families Citing this family (26)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2016054475A1 (en) * | 2014-10-03 | 2016-04-07 | The Johns Hopkins University | Compositions and methods for treating autism spectrum disorders |
EP2849737B1 (en) | 2012-07-05 | 2019-09-11 | Nutramax Laboratories, Inc. | Compositions comprising sulforaphane or a sulforaphane precursor and a mushroom extract or powder |
BR112015023190A2 (pt) | 2013-03-14 | 2017-07-18 | Univ Florida | regulação de câncer com o uso de compostos e/ou dieta naturais |
US20140275235A1 (en) * | 2013-03-15 | 2014-09-18 | Loic Pierre Deleyrolle | Treatment of Proliferative Disorders |
US20160030530A1 (en) * | 2013-03-15 | 2016-02-04 | Nutramax Laboratories, Inc. | Sulforaphane/sulforaphane precursor and phytosterol/phytostanol compositions |
KR101515573B1 (ko) * | 2014-11-07 | 2015-04-28 | 주식회사 파미니티 | 뉴그린 추출물을 유효성분으로 함유하는 해독용 조성물 |
CN107106628B (zh) | 2014-12-22 | 2021-01-12 | 荷兰联合利华有限公司 | 毛发组合物 |
JP2018513123A (ja) | 2015-03-12 | 2018-05-24 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | Rorガンマ阻害剤を用いてがんを治療するための方法 |
US11020372B2 (en) | 2015-03-24 | 2021-06-01 | University Of Florida Research Foundation, Incorporated | Dietary and natural product management of negative side effects of cancer treatment |
US11147825B2 (en) | 2015-06-26 | 2021-10-19 | Plant Bioscience Limited | Glucoraphnin for use in the treatment and/or prevention of diabetes mellitus |
BR112017027836A2 (pt) * | 2015-06-26 | 2018-09-04 | Univ Florida | método para o tratamento de inflamação usando compostos naturais e/ou dieta |
WO2017013239A1 (en) * | 2015-07-22 | 2017-01-26 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Nrf2 activators for the treatment of mycobacterial infections |
EP3123874B1 (en) * | 2015-07-28 | 2018-05-02 | Fundacíon Tecnalia Research & Innovation | Formulations comprising glucosinolates and myrosinase |
GB201605013D0 (en) * | 2016-03-24 | 2016-05-11 | Inst Of Food Res | S-methylcysteine sulfoxide for prostate cancer treatment |
US11357250B2 (en) | 2016-08-15 | 2022-06-14 | Summit Innovation Labs LLC | Treatment and prevention of diabetes and obesity |
US11344575B2 (en) * | 2016-08-15 | 2022-05-31 | Summit Innovation Labs, LLC | Vascular calcification prevention and treatment |
US10925304B2 (en) * | 2016-12-28 | 2021-02-23 | Productive Aging Laboratory, Co., Ltd. | Method for treating chronic fatigue syndrome, idiopathic chronic fatigue, and fibromyalgia |
JP7057070B2 (ja) | 2017-06-21 | 2022-04-19 | カゴメ株式会社 | 粉末食品、及びその製造方法、並びに粉末食品のミロシナーゼ活性促進方法 |
AU2018340868B2 (en) * | 2017-09-28 | 2022-05-12 | Commonwealth Scientific And Industrial Research Organisation | Isothiocyanate containing Brassicaceae products and method of preparation thereof |
WO2019171397A1 (en) * | 2018-03-05 | 2019-09-12 | Laila Nutraceuticals | Synergistic herbal compositions for the treatment of obesity and overweight |
WO2022047212A1 (en) * | 2020-08-27 | 2022-03-03 | Arizona Board Of Regents On Behalf Of The University Of Arizona | Compositions and methods for treating neurodegenerative disorders |
US11801273B2 (en) | 2020-12-23 | 2023-10-31 | Church & Dwight Co., Inc. | Compositions and methods to increase production of isothiocyanates |
CN112574161A (zh) * | 2021-01-19 | 2021-03-30 | 江苏德和生物科技有限公司 | 一种富含egc的非酯型茶多酚的制备方法 |
JP7288474B2 (ja) | 2021-03-10 | 2023-06-07 | プライムプラネットエナジー&ソリューションズ株式会社 | 非水電解質二次電池の製造方法、および負極活物質 |
EP4346861A1 (en) | 2021-05-26 | 2024-04-10 | Nutramax Laboratories, Inc. | Compositions comprising sulforaphane or a sulforaphane precursor and moringa plant components |
US20230364133A1 (en) * | 2022-05-10 | 2023-11-16 | Melaleuca, Inc. | Dietary supplement compositions |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1149986A (zh) * | 1995-09-27 | 1997-05-21 | 安利公司 | 芸苔属蔬菜增补剂及其制作方法 |
CN101514174A (zh) * | 2009-02-24 | 2009-08-26 | 黑龙江八一农垦大学 | 一种从西兰花芽苗菜中提取多功能莱菔硫烷的方法 |
CN101553134A (zh) * | 2006-02-10 | 2009-10-07 | 曼纳泰克公司 | 增强吸收及生物利用的全天然多种维生素和多种矿物质膳食补充剂制剂 |
CN102450534A (zh) * | 2010-10-26 | 2012-05-16 | 宁波海逸生物科技有限公司 | 一种增强免疫力功能的西灵胶囊配方 |
CN102526445A (zh) * | 2011-11-07 | 2012-07-04 | 宁波海逸生物科技有限公司 | 一种增强免疫力、缓解体力疲劳、抗肿瘤功能的保健药物配方 |
Family Cites Families (74)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE3442639A1 (de) | 1984-11-22 | 1986-05-22 | Dr. Madaus & Co, 5000 Köln | Flavolignanderivate, verfahren zu deren herstellung und arzneimittel, die diese verbindungen enthalten |
US5032401A (en) * | 1989-06-15 | 1991-07-16 | Alpha Beta Technology | Glucan drug delivery system and adjuvant |
US5223491A (en) | 1989-11-09 | 1993-06-29 | Donzis Byron A | Method for revitalizing skin by applying topically water insoluble glucan |
US5411986A (en) | 1993-03-12 | 1995-05-02 | The Johns Hopkins University | Chemoprotective isothiocyanates |
JPH07252148A (ja) * | 1994-10-08 | 1995-10-03 | Masahiro Nagahama | 糖尿病治療薬 |
US5576015A (en) | 1995-03-02 | 1996-11-19 | Donzis; Byron A. | Substantially purified beta (1,3) finely ground yeast cell wall glucan composition with dermatological and nutritional uses |
US5725895B1 (en) | 1995-09-15 | 2000-10-10 | Hopkins J School Of Medicine | Method of preparing food product from cruciferous seeds |
JP3041232B2 (ja) | 1995-11-16 | 2000-05-15 | 日本ケミカルリサーチ株式会社 | 癌転移抑制剤 |
JP2918834B2 (ja) | 1995-12-25 | 1999-07-12 | 美穂 田中 | シイタケエキス粉末の製造法 |
JP2859843B2 (ja) | 1996-03-08 | 1999-02-24 | 株式会社雪国まいたけ | マイタケから抽出した抗腫瘍物質 |
US6242018B1 (en) | 1997-04-11 | 2001-06-05 | Johns Hopkins School Of Medicine | Cancer Chemoprotective food products |
US20010000472A1 (en) | 1998-02-27 | 2001-04-26 | Nutramax Laboratories, Inc. | L-ergothioneine, milk thistle, and s-adenosylmethionine for the prevention, treatment and repair of liver damage |
AU3308999A (en) | 1998-02-27 | 1999-09-15 | Nutramax Laboratories, Inc. | L-ergothioneine, milk thistle, and s-adenosylmethionine for the prevention, treatment and repair of liver damage |
US6521818B1 (en) | 1998-07-01 | 2003-02-18 | John Hopkins School Of Medicine | Development of novel highly chemoprotectant crucifer germplasm |
CA2339473A1 (en) * | 1998-08-04 | 2000-02-17 | John V. Kosbab | Nutrient and therapeutic compositions for the treatment of cancer |
JP4308350B2 (ja) | 1998-11-27 | 2009-08-05 | 小林製薬株式会社 | シイタケ菌糸体抽出物を含有するlak活性スクリーニング物質およびそれを用いたlak活性スクリーニング法 |
EP1239826A2 (de) | 1999-12-20 | 2002-09-18 | Cognis France S.A. | Kosmetische und/oder pharmazeutische zubereitungen |
WO2001054673A1 (en) | 2000-01-31 | 2001-08-02 | The University Of British Columbia | Method for preparing and administering medicinal plant material |
JP2002051732A (ja) * | 2000-06-12 | 2002-02-19 | Access Business Group Llc | 食事による植物性化学物質欠乏症を矯正する組成物及び方法 |
WO2002015722A2 (en) * | 2000-08-21 | 2002-02-28 | Fahey Jed W | Treatment of helicobacter with isothiocyanates |
JP3504612B2 (ja) | 2000-12-28 | 2004-03-08 | 株式会社東洋新薬 | 栄養補助食品 |
US6582723B2 (en) | 2001-05-03 | 2003-06-24 | Wayne F. Gorsek | Cancer immune composition for prevention and treatment of individuals |
US8017160B2 (en) * | 2003-08-15 | 2011-09-13 | Russell Jaffe | Enhancement of magnesium uptake in mammals |
JP2005073508A (ja) | 2003-08-28 | 2005-03-24 | Asahi Denka Kogyo Kk | 食用または薬用植物を含有する飲料 |
ITMI20040696A1 (it) | 2004-04-08 | 2004-07-08 | Aboca S P A | Composizioni per tisane arricchite con estratti secchi vegetali |
WO2005107496A1 (ja) | 2004-05-06 | 2005-11-17 | Maruasaen Corporation | 生キノコエキス製造方法、エキス及びエキス配合物 |
JP4126053B2 (ja) * | 2004-05-06 | 2008-07-30 | 堯 近藤 | 鹿角霊芝を含有した健康食品の製造方法 |
RU2292899C2 (ru) | 2004-06-29 | 2007-02-10 | Дмитрий Николаевич Мясников | Средство и способ профилактики и уменьшения неблагоприятных проявлений острой алкогольной интоксикации (варианты) и способ получения средства |
US20060264497A1 (en) * | 2005-03-28 | 2006-11-23 | Zeligs Michael A | Diindolylmethane-based compositions and methods of use thereof for promoting oral mucosal and bone health |
EP1709969A1 (en) | 2005-04-07 | 2006-10-11 | Praktijkonderzoek Plant en Omgeving B.V. | Health promoting dairy and food products containing mushroom glucan produced through fermentation of Grifola frondosa |
KR100661032B1 (ko) * | 2005-04-19 | 2006-12-22 | 주식회사한국야쿠르트 | 간 기능 개선, 혈중 알코올 감소 및 항산화에 유효한조성물 |
NZ563852A (en) * | 2005-04-29 | 2011-07-29 | Univ Johns Hopkins | Methods of supressing UV light-induced skin carcinogenesis |
US8124135B2 (en) | 2005-05-24 | 2012-02-28 | Vdf Futureceuticals, Inc. | Compositions and methods for reduction of LDL oxidation |
US7887852B2 (en) * | 2005-06-03 | 2011-02-15 | Soft Gel Technologies, Inc. | Soft gel capsules containing polymethoxylated flavones and palm oil tocotrienols |
DE102005033616A1 (de) * | 2005-07-19 | 2007-01-25 | Biopro Ag Biological Products | Verfahren zur Herstellung von Extrakten aus Brassica-Arten und ihre Verwendung |
US20070021376A1 (en) * | 2005-07-21 | 2007-01-25 | Suracell, Inc. | Supplement composition and method of use in enhancement of methylation process |
US7597910B2 (en) | 2005-08-20 | 2009-10-06 | Slgm Medical Research Institute | Compositions and methods for treating prostate disorders |
RU2319494C2 (ru) * | 2005-11-11 | 2008-03-20 | РАНХЕЛЬ Хосе Анхель ОЛАЛДЕ | Синергетическая композиция растительного происхождения (варианты), способ лечения заболеваний с ее использованием |
US8323644B2 (en) | 2006-01-17 | 2012-12-04 | Sloan-Kettering Institute For Cancer Research | Therapy-enhancing glucan |
JP2007320947A (ja) * | 2006-05-30 | 2007-12-13 | Shonan Institute For Medical & Preventive Science | 血糖値上昇抑制剤 |
WO2007142130A1 (ja) | 2006-06-02 | 2007-12-13 | Heimat Co., Ltd. | マイタケ抽出物及びこれを含む皮脂産生を促進するための組成物 |
WO2008002175A1 (fr) * | 2006-06-29 | 2008-01-03 | Vulf Abramovich Laskin | Régime hebdomadaire destiné aux patients oncologiques et aux personnes ayant une durée de vie remarquablement longue |
US7803605B2 (en) | 2006-07-14 | 2010-09-28 | National Institute Of Advanced Industrial Science And Technology | Breeding method for yeast, yeast and a production method for glycoprotein or beta-glucan |
WO2008115583A1 (en) * | 2007-03-21 | 2008-09-25 | John Mini | Herbal treatments |
US20080254055A1 (en) | 2007-04-11 | 2008-10-16 | John Erich Oblong | Compositions for Regulation of Hair Growth |
US20080311192A1 (en) * | 2007-06-12 | 2008-12-18 | Kraft Foods Holdings, Inc. | Enteric-Coated Glucosinolates And Beta-Thioglucosidases |
WO2009008006A2 (en) | 2007-07-06 | 2009-01-15 | Lupin Limited | Pharmaceutical compositions for gastrointestinal drug delivery |
CZ305673B6 (cs) | 2007-08-02 | 2016-02-03 | Irel, Spol. S R. O. | Mechanicky upravený plod ostropestřce mariánského a způsob jeho úpravy |
ES2325291B1 (es) | 2007-10-04 | 2010-04-22 | Madaus S A | "uso de un extracto de silybum marianum" |
WO2009051739A1 (en) | 2007-10-16 | 2009-04-23 | Johns Hopkins University | Methods for protecting the skin from radiation insults |
WO2009063885A1 (ja) | 2007-11-13 | 2009-05-22 | Heimat Co., Ltd. | マイタケ抽出物及びこれを含むヒアルロン酸(ヒアルロナン)産生を促進するための組成物 |
ITMI20080172A1 (it) * | 2008-02-05 | 2009-08-06 | Bios Line Spa | Formulazioni orali per la protezione delle vie respiratorie con particolare riferimento ai fenomeni infiammatori e neoplastici |
US20090252758A1 (en) * | 2008-04-07 | 2009-10-08 | Mazed Mohammad A | Nutritional supplement for the prevention of cardiovascular disease, alzheimer's disease, diabetes, and regulation and reduction of blood sugar and insulin resistance |
US7923044B2 (en) | 2008-07-15 | 2011-04-12 | Paradise Herbs & Essentials, Inc. | Composition for high-ORAC value dietary supplement |
KR20100016876A (ko) * | 2008-08-05 | 2010-02-16 | 오춘근 | 다이어트 및 당뇨에 유용한 기능성 혼합곡물 |
EP2213280A1 (en) | 2009-01-30 | 2010-08-04 | DSM IP Assets B.V. | Formulations comprising glucosinolate and myrosinase |
US8828953B2 (en) * | 2009-04-20 | 2014-09-09 | NaZura BioHealth, Inc. | Chemosensory receptor ligand-based therapies |
JP2010259424A (ja) | 2009-05-11 | 2010-11-18 | Hisako Arai | 簡単に摂取できる副食の調理法。 |
US8377473B2 (en) * | 2009-07-01 | 2013-02-19 | Magceutics, Inc. | Slow release magnesium composition and uses thereof |
WO2011060585A1 (zh) * | 2009-11-20 | 2011-05-26 | 天津天狮生物发展有限公司 | 含有五色果蔬精华的咀嚼片剂及其制备方法 |
WO2011076154A1 (en) | 2009-12-22 | 2011-06-30 | Irel, Spol. S R.O. | Feed supplement based on milk thistle, method of its production and its use |
KR101079643B1 (ko) | 2010-01-12 | 2011-11-04 | 이현재 | 신장 기능 강화용 식품 조성물 및 그 제조방법 |
WO2011099665A1 (ko) * | 2010-02-12 | 2011-08-18 | 주식회사 케이씨아이 | 천연 원료 추출물을 포함하는 항균 조성물, 복합 천연 방부제 및 이들의 제조방법 |
US20110206721A1 (en) * | 2010-02-19 | 2011-08-25 | Vijaya Nair | Fermented soy nutritional supplements including mushroom components |
US20120021079A1 (en) | 2010-02-23 | 2012-01-26 | Brett Justin West | Garcinia Mangostana L. and Iridoid Based Formulations |
WO2011149835A1 (en) * | 2010-05-24 | 2011-12-01 | Max International, Llc | Compositions and beverages comprising nutrients, vitamins, sugars, cysteine, and/or sugar-cysteine products |
DE102010022587A1 (de) * | 2010-05-28 | 2011-12-01 | Wilfried Rühle | Magensaftresistente Zusammensetzung zur oralen Einnahme von pflanzenbasierten Komponenten zur Prävention von Darmkrebs |
ES2382299B1 (es) | 2010-11-11 | 2013-05-07 | Consejo Superior De Investigaciones Científicas (Csic) | Polvo vegetal para alimentación y protección vegetal y métodos de preparación. |
NZ589578A (en) * | 2010-11-29 | 2013-03-28 | Comvita Ltd | Cancer Chemoprotective Product including glucosinolate and myrosinase |
CN102526455A (zh) | 2010-12-16 | 2012-07-04 | 天津中敖生物科技有限公司 | 具有清肺化痰功能的家畜用中药组合物及其制备方法 |
WO2012116018A1 (en) * | 2011-02-22 | 2012-08-30 | Caudill Seed Company, Inc. | Spray dried myrosinase and use to produce isothiocyanates |
WO2012122295A2 (en) * | 2011-03-07 | 2012-09-13 | Ned Biosystems, Inc. | Treatment for pancreatic adenocarcinoma and other cancers of epithelial origin |
US20130045273A1 (en) * | 2011-08-19 | 2013-02-21 | John Cuomo | Methods for using nutritional supplements containing lipoic acids and sulfur containing compounds |
EP2849737B1 (en) | 2012-07-05 | 2019-09-11 | Nutramax Laboratories, Inc. | Compositions comprising sulforaphane or a sulforaphane precursor and a mushroom extract or powder |
-
2013
- 2013-07-03 EP EP13813686.6A patent/EP2849737B1/en active Active
- 2013-07-03 JP JP2015520676A patent/JP6436443B2/ja active Active
- 2013-07-03 CA CA2877356A patent/CA2877356C/en active Active
- 2013-07-03 CA CA2877338A patent/CA2877338C/en active Active
- 2013-07-03 JP JP2015520673A patent/JP6548573B2/ja active Active
- 2013-07-03 WO PCT/US2013/049224 patent/WO2014008341A2/en active Application Filing
- 2013-07-03 ES ES13813686T patent/ES2755757T3/es active Active
- 2013-07-03 US US14/412,180 patent/US20150174213A1/en not_active Abandoned
- 2013-07-03 EP EP18182247.9A patent/EP3409280B1/en active Active
- 2013-07-03 EP EP20209762.2A patent/EP3821895A1/en active Pending
- 2013-07-03 CA CA2877329A patent/CA2877329C/en active Active
- 2013-07-03 US US14/412,176 patent/US10688158B2/en active Active
- 2013-07-03 ES ES18182247T patent/ES2877326T3/es active Active
- 2013-07-03 EP EP13812796.4A patent/EP2849736B1/en active Active
- 2013-07-03 WO PCT/US2013/049261 patent/WO2014008361A2/en active Application Filing
- 2013-07-03 EP EP19189657.0A patent/EP3666277A1/en active Pending
- 2013-07-03 WO PCT/US2013/049248 patent/WO2014008353A2/en active Application Filing
- 2013-07-03 CA CA3112680A patent/CA3112680C/en active Active
- 2013-07-03 CN CN201810409516.XA patent/CN108355136B/zh active Active
- 2013-07-03 PL PL13812796T patent/PL2849736T3/pl unknown
- 2013-07-03 WO PCT/US2013/049267 patent/WO2014008366A2/en active Application Filing
- 2013-07-03 US US14/412,191 patent/US10960057B2/en active Active
- 2013-07-03 PL PL18182247T patent/PL3409280T3/pl unknown
- 2013-07-03 RU RU2015103499A patent/RU2666953C2/ru active
- 2013-07-03 AU AU2013286713A patent/AU2013286713B2/en active Active
- 2013-07-03 RU RU2015103498A patent/RU2680387C2/ru active
- 2013-07-03 CN CN201380035766.7A patent/CN104427981B/zh active Active
- 2013-07-03 CA CA2877393A patent/CA2877393C/en active Active
- 2013-07-03 AU AU2013286721A patent/AU2013286721B2/en active Active
- 2013-07-03 ES ES13812796T patent/ES2700223T3/es active Active
- 2013-07-03 US US14/412,189 patent/US20150174093A1/en not_active Abandoned
- 2013-07-04 TW TW102124064A patent/TW201402130A/zh unknown
- 2013-07-04 TW TW105102752A patent/TWI606830B/zh active
- 2013-07-04 TW TW102124065A patent/TWI580425B/zh active
- 2013-07-04 TW TW102124062A patent/TW201402128A/zh unknown
- 2013-07-04 TW TW106101594A patent/TWI637745B/zh active
- 2013-07-04 TW TW102124063A patent/TW201402129A/zh unknown
-
2014
- 2014-12-30 US US14/586,698 patent/US20150118305A1/en not_active Abandoned
- 2014-12-30 US US14/586,704 patent/US20150118306A1/en not_active Abandoned
- 2014-12-30 US US14/586,711 patent/US20150118304A1/en not_active Abandoned
- 2014-12-30 US US14/586,765 patent/US9421183B2/en active Active
-
2016
- 2016-08-23 US US15/244,374 patent/US10583178B2/en active Active
-
2018
- 2018-06-15 AU AU2018204283A patent/AU2018204283B2/en active Active
- 2018-06-25 AU AU2018204604A patent/AU2018204604C1/en active Active
- 2018-11-06 JP JP2018208602A patent/JP6777366B2/ja active Active
- 2018-11-22 JP JP2018219617A patent/JP2019023245A/ja active Pending
-
2019
- 2019-12-03 US US16/701,644 patent/US11654186B2/en active Active
-
2020
- 2020-05-04 US US16/865,529 patent/US11224639B2/en active Active
- 2020-05-14 JP JP2020085417A patent/JP7068383B2/ja active Active
- 2020-08-14 AU AU2020217440A patent/AU2020217440B2/en active Active
- 2020-08-28 AU AU2020223773A patent/AU2020223773B2/en active Active
- 2020-08-31 US US17/007,067 patent/US20210008176A1/en active Pending
- 2020-10-06 JP JP2020168976A patent/JP7109132B2/ja active Active
- 2020-11-27 JP JP2020196733A patent/JP7232806B2/ja active Active
-
2021
- 2021-02-18 US US17/178,664 patent/US20210169997A1/en active Pending
- 2021-12-23 US US17/560,494 patent/US20220118062A1/en active Pending
-
2022
- 2022-02-17 JP JP2022022783A patent/JP2022059053A/ja active Pending
- 2022-06-02 AU AU2022203801A patent/AU2022203801A1/en active Pending
- 2022-07-14 JP JP2022113426A patent/JP7458443B2/ja active Active
-
2023
- 2023-07-26 AU AU2023208131A patent/AU2023208131A1/en active Pending
- 2023-12-11 JP JP2023208549A patent/JP2024023619A/ja active Pending
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1149986A (zh) * | 1995-09-27 | 1997-05-21 | 安利公司 | 芸苔属蔬菜增补剂及其制作方法 |
CN101553134A (zh) * | 2006-02-10 | 2009-10-07 | 曼纳泰克公司 | 增强吸收及生物利用的全天然多种维生素和多种矿物质膳食补充剂制剂 |
CN101514174A (zh) * | 2009-02-24 | 2009-08-26 | 黑龙江八一农垦大学 | 一种从西兰花芽苗菜中提取多功能莱菔硫烷的方法 |
CN102450534A (zh) * | 2010-10-26 | 2012-05-16 | 宁波海逸生物科技有限公司 | 一种增强免疫力功能的西灵胶囊配方 |
CN102526445A (zh) * | 2011-11-07 | 2012-07-04 | 宁波海逸生物科技有限公司 | 一种增强免疫力、缓解体力疲劳、抗肿瘤功能的保健药物配方 |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN110946996A (zh) * | 2019-05-08 | 2020-04-03 | 深圳福山生物科技有限公司 | 包含萝卜硫苷的组合物及其用途 |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US11654186B2 (en) | Compositions comprising sulforaphane or a sulforaphane precursor and a mushroom extract or powder | |
US20220387535A1 (en) | Compositions comprising sulforaphane or a sulforaphane precursor and moringa plant components |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant |