CN110139643A - 一种用于治疗代谢紊乱综合征、炎症及其并发症的药物成分 - Google Patents
一种用于治疗代谢紊乱综合征、炎症及其并发症的药物成分 Download PDFInfo
- Publication number
- CN110139643A CN110139643A CN201780082728.5A CN201780082728A CN110139643A CN 110139643 A CN110139643 A CN 110139643A CN 201780082728 A CN201780082728 A CN 201780082728A CN 110139643 A CN110139643 A CN 110139643A
- Authority
- CN
- China
- Prior art keywords
- cancer
- disease
- equal
- virus
- drug
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 239000003814 drug Substances 0.000 title claims abstract description 117
- 229940079593 drug Drugs 0.000 title claims abstract description 93
- 206010061218 Inflammation Diseases 0.000 title claims description 12
- 230000004054 inflammatory process Effects 0.000 title claims description 12
- 208000030159 metabolic disease Diseases 0.000 title claims description 9
- 208000011580 syndromic disease Diseases 0.000 title description 3
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 61
- 201000011510 cancer Diseases 0.000 claims abstract description 51
- 206010012601 diabetes mellitus Diseases 0.000 claims abstract description 33
- 235000013985 cinnamic acid Nutrition 0.000 claims abstract description 30
- WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 claims abstract description 29
- WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 claims abstract description 29
- 229930016911 cinnamic acid Natural products 0.000 claims abstract description 29
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 claims abstract description 29
- KZJWDPNRJALLNS-VJSFXXLFSA-N sitosterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CC[C@@H](CC)C(C)C)[C@@]1(C)CC2 KZJWDPNRJALLNS-VJSFXXLFSA-N 0.000 claims abstract description 27
- XMGQYMWWDOXHJM-JTQLQIEISA-N (+)-α-limonene Chemical compound CC(=C)[C@@H]1CCC(C)=CC1 XMGQYMWWDOXHJM-JTQLQIEISA-N 0.000 claims abstract description 26
- MQYXUWHLBZFQQO-QGTGJCAVSA-N lupeol Chemical compound C1C[C@H](O)C(C)(C)[C@@H]2CC[C@@]3(C)[C@]4(C)CC[C@@]5(C)CC[C@@H](C(=C)C)[C@@H]5[C@H]4CC[C@@H]3[C@]21C MQYXUWHLBZFQQO-QGTGJCAVSA-N 0.000 claims abstract description 26
- PKGKOZOYXQMJNG-UHFFFAOYSA-N lupeol Natural products CC(=C)C1CC2C(C)(CCC3C4(C)CCC5C(C)(C)C(O)CCC5(C)C4CCC23C)C1 PKGKOZOYXQMJNG-UHFFFAOYSA-N 0.000 claims abstract description 26
- 208000032928 Dyslipidaemia Diseases 0.000 claims abstract description 24
- 208000017170 Lipid metabolism disease Diseases 0.000 claims abstract description 24
- 239000012141 concentrate Substances 0.000 claims abstract description 24
- 208000015181 infectious disease Diseases 0.000 claims abstract description 23
- 239000000203 mixture Substances 0.000 claims abstract description 23
- NDRKNOADOZHUQR-UHFFFAOYSA-N 1-chloro-4-[cyclohexyloxy(methoxy)phosphoryl]sulfanylbenzene Chemical compound C=1C=C(Cl)C=CC=1SP(=O)(OC)OC1CCCCC1 NDRKNOADOZHUQR-UHFFFAOYSA-N 0.000 claims abstract description 22
- 239000004615 ingredient Substances 0.000 claims abstract description 22
- 210000000577 adipose tissue Anatomy 0.000 claims abstract description 18
- 208000008589 Obesity Diseases 0.000 claims abstract description 17
- 235000020824 obesity Nutrition 0.000 claims abstract description 16
- PFTAWBLQPZVEMU-UKRRQHHQSA-N (-)-epicatechin Chemical compound C1([C@H]2OC3=CC(O)=CC(O)=C3C[C@H]2O)=CC=C(O)C(O)=C1 PFTAWBLQPZVEMU-UKRRQHHQSA-N 0.000 claims abstract description 13
- PFTAWBLQPZVEMU-ZFWWWQNUSA-N (+)-epicatechin Natural products C1([C@@H]2OC3=CC(O)=CC(O)=C3C[C@@H]2O)=CC=C(O)C(O)=C1 PFTAWBLQPZVEMU-ZFWWWQNUSA-N 0.000 claims abstract description 12
- 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 abstract description 12
- LPTRNLNOHUVQMS-UHFFFAOYSA-N epicatechin Natural products Cc1cc(O)cc2OC(C(O)Cc12)c1ccc(O)c(O)c1 LPTRNLNOHUVQMS-UHFFFAOYSA-N 0.000 claims abstract description 12
- 235000012734 epicatechin Nutrition 0.000 claims abstract description 12
- 235000012754 curcumin Nutrition 0.000 claims abstract description 6
- 239000004148 curcumin Substances 0.000 claims abstract description 6
- 229940109262 curcumin Drugs 0.000 claims abstract description 6
- 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 abstract description 6
- 230000002265 prevention Effects 0.000 claims abstract description 6
- 210000004027 cell Anatomy 0.000 claims description 46
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 42
- 201000010099 disease Diseases 0.000 claims description 39
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 claims description 34
- 241000700605 Viruses Species 0.000 claims description 31
- 150000002632 lipids Chemical class 0.000 claims description 27
- 210000004369 blood Anatomy 0.000 claims description 24
- 239000008280 blood Substances 0.000 claims description 24
- 230000001717 pathogenic effect Effects 0.000 claims description 22
- 108090000623 proteins and genes Proteins 0.000 claims description 19
- 244000052769 pathogen Species 0.000 claims description 18
- 102000004169 proteins and genes Human genes 0.000 claims description 18
- 102000004877 Insulin Human genes 0.000 claims description 17
- 108090001061 Insulin Proteins 0.000 claims description 17
- 229940125396 insulin Drugs 0.000 claims description 17
- 230000000694 effects Effects 0.000 claims description 16
- -1 fusion inhibitor Substances 0.000 claims description 15
- 208000030507 AIDS Diseases 0.000 claims description 14
- 201000001320 Atherosclerosis Diseases 0.000 claims description 14
- 241000894006 Bacteria Species 0.000 claims description 14
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 14
- 230000004770 neurodegeneration Effects 0.000 claims description 13
- 239000003472 antidiabetic agent Substances 0.000 claims description 12
- 238000002360 preparation method Methods 0.000 claims description 12
- 206010022489 Insulin Resistance Diseases 0.000 claims description 11
- 230000003178 anti-diabetic effect Effects 0.000 claims description 11
- 241000725303 Human immunodeficiency virus Species 0.000 claims description 10
- 230000005764 inhibitory process Effects 0.000 claims description 10
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 10
- 208000024827 Alzheimer disease Diseases 0.000 claims description 9
- 208000037976 chronic inflammation Diseases 0.000 claims description 9
- 239000000893 inhibin Substances 0.000 claims description 9
- ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 claims description 9
- 230000009885 systemic effect Effects 0.000 claims description 9
- 239000002246 antineoplastic agent Substances 0.000 claims description 8
- 229940041181 antineoplastic drug Drugs 0.000 claims description 8
- 239000003795 chemical substances by application Substances 0.000 claims description 8
- 210000005229 liver cell Anatomy 0.000 claims description 8
- 210000004379 membrane Anatomy 0.000 claims description 8
- 239000012528 membrane Substances 0.000 claims description 8
- 208000034189 Sclerosis Diseases 0.000 claims description 7
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 7
- 230000000798 anti-retroviral effect Effects 0.000 claims description 7
- 230000005784 autoimmunity Effects 0.000 claims description 7
- 230000036039 immunity Effects 0.000 claims description 7
- JEIPFZHSYJVQDO-UHFFFAOYSA-N iron(III) oxide Inorganic materials O=[Fe]O[Fe]=O JEIPFZHSYJVQDO-UHFFFAOYSA-N 0.000 claims description 7
- 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 6
- 241000701044 Human gammaherpesvirus 4 Species 0.000 claims description 6
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 claims description 6
- 241000711975 Vesicular stomatitis virus Species 0.000 claims description 6
- 230000002924 anti-infective effect Effects 0.000 claims description 6
- 229960005475 antiinfective agent Drugs 0.000 claims description 6
- 210000004556 brain Anatomy 0.000 claims description 6
- 230000004064 dysfunction Effects 0.000 claims description 6
- 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 claims description 6
- 208000031886 HIV Infections Diseases 0.000 claims description 5
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 claims description 5
- 206010060862 Prostate cancer Diseases 0.000 claims description 5
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 5
- 238000006243 chemical reaction Methods 0.000 claims description 5
- OLNTVTPDXPETLC-XPWALMASSA-N ezetimibe Chemical compound N1([C@@H]([C@H](C1=O)CC[C@H](O)C=1C=CC(F)=CC=1)C=1C=CC(O)=CC=1)C1=CC=C(F)C=C1 OLNTVTPDXPETLC-XPWALMASSA-N 0.000 claims description 5
- 229960000815 ezetimibe Drugs 0.000 claims description 5
- 208000023275 Autoimmune disease Diseases 0.000 claims description 4
- 206010006187 Breast cancer Diseases 0.000 claims description 4
- 208000026310 Breast neoplasm Diseases 0.000 claims description 4
- 206010008190 Cerebrovascular accident Diseases 0.000 claims description 4
- 206010009944 Colon cancer Diseases 0.000 claims description 4
- 241000713772 Human immunodeficiency virus 1 Species 0.000 claims description 4
- 102100024295 Maltase-glucoamylase Human genes 0.000 claims description 4
- 241000712079 Measles morbillivirus Species 0.000 claims description 4
- 208000005764 Peripheral Arterial Disease Diseases 0.000 claims description 4
- 208000030831 Peripheral arterial occlusive disease Diseases 0.000 claims description 4
- 208000006011 Stroke Diseases 0.000 claims description 4
- 229940100389 Sulfonylurea Drugs 0.000 claims description 4
- 108010028144 alpha-Glucosidases Proteins 0.000 claims description 4
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 4
- 230000003115 biocidal effect Effects 0.000 claims description 4
- 208000037893 chronic inflammatory disorder Diseases 0.000 claims description 4
- 210000001072 colon Anatomy 0.000 claims description 4
- 229960002297 fenofibrate Drugs 0.000 claims description 4
- YMTINGFKWWXKFG-UHFFFAOYSA-N fenofibrate Chemical compound C1=CC(OC(C)(C)C(=O)OC(C)C)=CC=C1C(=O)C1=CC=C(Cl)C=C1 YMTINGFKWWXKFG-UHFFFAOYSA-N 0.000 claims description 4
- 230000004927 fusion Effects 0.000 claims description 4
- 210000003734 kidney Anatomy 0.000 claims description 4
- 239000002777 nucleoside Substances 0.000 claims description 4
- 125000003835 nucleoside group Chemical group 0.000 claims description 4
- 231100000614 poison Toxicity 0.000 claims description 4
- 239000000837 restrainer Substances 0.000 claims description 4
- STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 claims description 3
- 206010002383 Angina Pectoris Diseases 0.000 claims description 3
- 206010005003 Bladder cancer Diseases 0.000 claims description 3
- 208000003174 Brain Neoplasms Diseases 0.000 claims description 3
- 208000011691 Burkitt lymphomas Diseases 0.000 claims description 3
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 claims description 3
- GAGWJHPBXLXJQN-UORFTKCHSA-N Capecitabine Chemical compound C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](C)O1 GAGWJHPBXLXJQN-UORFTKCHSA-N 0.000 claims description 3
- GAGWJHPBXLXJQN-UHFFFAOYSA-N Capecitabine Natural products C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1C1C(O)C(O)C(C)O1 GAGWJHPBXLXJQN-UHFFFAOYSA-N 0.000 claims description 3
- 201000009030 Carcinoma Diseases 0.000 claims description 3
- 229920001268 Cholestyramine Polymers 0.000 claims description 3
- 208000011231 Crohn disease Diseases 0.000 claims description 3
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 claims description 3
- 241000701022 Cytomegalovirus Species 0.000 claims description 3
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 claims description 3
- WEAHRLBPCANXCN-UHFFFAOYSA-N Daunomycin Natural products CCC1(O)CC(OC2CC(N)C(O)C(C)O2)c3cc4C(=O)c5c(OC)cccc5C(=O)c4c(O)c3C1 WEAHRLBPCANXCN-UHFFFAOYSA-N 0.000 claims description 3
- 241000588724 Escherichia coli Species 0.000 claims description 3
- HKVAMNSJSFKALM-GKUWKFKPSA-N Everolimus Chemical compound C1C[C@@H](OCCO)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 HKVAMNSJSFKALM-GKUWKFKPSA-N 0.000 claims description 3
- 241000710831 Flavivirus Species 0.000 claims description 3
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 claims description 3
- 208000022072 Gallbladder Neoplasms Diseases 0.000 claims description 3
- 230000010558 Gene Alterations Effects 0.000 claims description 3
- 108010024636 Glutathione Proteins 0.000 claims description 3
- 208000030836 Hashimoto thyroiditis Diseases 0.000 claims description 3
- 208000017604 Hodgkin disease Diseases 0.000 claims description 3
- 241000713340 Human immunodeficiency virus 2 Species 0.000 claims description 3
- 241000714192 Human spumaretrovirus Species 0.000 claims description 3
- 102000014150 Interferons Human genes 0.000 claims description 3
- 108010050904 Interferons Proteins 0.000 claims description 3
- 208000007766 Kaposi sarcoma Diseases 0.000 claims description 3
- 239000002147 L01XE04 - Sunitinib Substances 0.000 claims description 3
- 206010061523 Lip and/or oral cavity cancer Diseases 0.000 claims description 3
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 3
- 206010029164 Nephrotic syndrome Diseases 0.000 claims description 3
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 3
- 206010035226 Plasma cell myeloma Diseases 0.000 claims description 3
- 229940079156 Proteasome inhibitor Drugs 0.000 claims description 3
- 208000010378 Pulmonary Embolism Diseases 0.000 claims description 3
- 241000702670 Rotavirus Species 0.000 claims description 3
- 208000021386 Sjogren Syndrome Diseases 0.000 claims description 3
- 208000005718 Stomach Neoplasms Diseases 0.000 claims description 3
- 101710183280 Topoisomerase Proteins 0.000 claims description 3
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 3
- 241000700647 Variola virus Species 0.000 claims description 3
- 201000004810 Vascular dementia Diseases 0.000 claims description 3
- 229930003268 Vitamin C Natural products 0.000 claims description 3
- 241000710886 West Nile virus Species 0.000 claims description 3
- 239000002253 acid Substances 0.000 claims description 3
- 230000001154 acute effect Effects 0.000 claims description 3
- 229960001686 afatinib Drugs 0.000 claims description 3
- ULXXDDBFHOBEHA-CWDCEQMOSA-N afatinib Chemical compound N1=CN=C2C=C(O[C@@H]3COCC3)C(NC(=O)/C=C/CN(C)C)=CC2=C1NC1=CC=C(F)C(Cl)=C1 ULXXDDBFHOBEHA-CWDCEQMOSA-N 0.000 claims description 3
- 230000032683 aging Effects 0.000 claims description 3
- 230000002152 alkylating effect Effects 0.000 claims description 3
- 230000000340 anti-metabolite Effects 0.000 claims description 3
- 239000003005 anticarcinogenic agent Substances 0.000 claims description 3
- 229940100197 antimetabolite Drugs 0.000 claims description 3
- 239000002256 antimetabolite Substances 0.000 claims description 3
- 229940125687 antiparasitic agent Drugs 0.000 claims description 3
- 239000003096 antiparasitic agent Substances 0.000 claims description 3
- 229960000397 bevacizumab Drugs 0.000 claims description 3
- 150000004283 biguanides Chemical class 0.000 claims description 3
- 229960002092 busulfan Drugs 0.000 claims description 3
- KVUAALJSMIVURS-ZEDZUCNESA-L calcium folinate Chemical compound [Ca+2].C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)N[C@@H](CCC([O-])=O)C([O-])=O)C=C1 KVUAALJSMIVURS-ZEDZUCNESA-L 0.000 claims description 3
- 235000008207 calcium folinate Nutrition 0.000 claims description 3
- 239000011687 calcium folinate Substances 0.000 claims description 3
- 229960004117 capecitabine Drugs 0.000 claims description 3
- 239000002775 capsule Substances 0.000 claims description 3
- 230000001413 cellular effect Effects 0.000 claims description 3
- 229960004630 chlorambucil Drugs 0.000 claims description 3
- JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 claims description 3
- 201000001352 cholecystitis Diseases 0.000 claims description 3
- 230000001684 chronic effect Effects 0.000 claims description 3
- 229960004397 cyclophosphamide Drugs 0.000 claims description 3
- STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 claims description 3
- 230000007812 deficiency Effects 0.000 claims description 3
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 claims description 3
- 208000016097 disease of metabolism Diseases 0.000 claims description 3
- 108010021916 duodenin Proteins 0.000 claims description 3
- VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 claims description 3
- 229960005420 etoposide Drugs 0.000 claims description 3
- 229960005167 everolimus Drugs 0.000 claims description 3
- 229960002949 fluorouracil Drugs 0.000 claims description 3
- 201000010175 gallbladder cancer Diseases 0.000 claims description 3
- 206010017758 gastric cancer Diseases 0.000 claims description 3
- 229960003180 glutathione Drugs 0.000 claims description 3
- 235000003969 glutathione Nutrition 0.000 claims description 3
- 208000002672 hepatitis B Diseases 0.000 claims description 3
- 206010073071 hepatocellular carcinoma Diseases 0.000 claims description 3
- 231100000844 hepatocellular carcinoma Toxicity 0.000 claims description 3
- 229940121372 histone deacetylase inhibitor Drugs 0.000 claims description 3
- 239000003276 histone deacetylase inhibitor Substances 0.000 claims description 3
- 229940124524 integrase inhibitor Drugs 0.000 claims description 3
- 239000002850 integrase inhibitor Substances 0.000 claims description 3
- 229940079322 interferon Drugs 0.000 claims description 3
- 229940043355 kinase inhibitor Drugs 0.000 claims description 3
- 201000007270 liver cancer Diseases 0.000 claims description 3
- 208000014018 liver neoplasm Diseases 0.000 claims description 3
- 201000005202 lung cancer Diseases 0.000 claims description 3
- 208000020816 lung neoplasm Diseases 0.000 claims description 3
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 3
- 229960004857 mitomycin Drugs 0.000 claims description 3
- 201000000050 myeloid neoplasm Diseases 0.000 claims description 3
- 208000010125 myocardial infarction Diseases 0.000 claims description 3
- LBWFXVZLPYTWQI-IPOVEDGCSA-N n-[2-(diethylamino)ethyl]-5-[(z)-(5-fluoro-2-oxo-1h-indol-3-ylidene)methyl]-2,4-dimethyl-1h-pyrrole-3-carboxamide;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.CCN(CC)CCNC(=O)C1=C(C)NC(\C=C/2C3=CC(F)=CC=C3NC\2=O)=C1C LBWFXVZLPYTWQI-IPOVEDGCSA-N 0.000 claims description 3
- 208000009928 nephrosis Diseases 0.000 claims description 3
- 231100001027 nephrosis Toxicity 0.000 claims description 3
- 210000000653 nervous system Anatomy 0.000 claims description 3
- 208000020717 oral cavity carcinoma Diseases 0.000 claims description 3
- 208000008798 osteoma Diseases 0.000 claims description 3
- 230000036542 oxidative stress Effects 0.000 claims description 3
- 239000000137 peptide hydrolase inhibitor Substances 0.000 claims description 3
- 239000003757 phosphotransferase inhibitor Substances 0.000 claims description 3
- 239000002574 poison Substances 0.000 claims description 3
- 208000005987 polymyositis Diseases 0.000 claims description 3
- 239000003207 proteasome inhibitor Substances 0.000 claims description 3
- 229940121896 radiopharmaceutical Drugs 0.000 claims description 3
- 239000012217 radiopharmaceutical Substances 0.000 claims description 3
- 230000002799 radiopharmaceutical effect Effects 0.000 claims description 3
- 201000001275 rectum cancer Diseases 0.000 claims description 3
- 229960004641 rituximab Drugs 0.000 claims description 3
- 201000000306 sarcoidosis Diseases 0.000 claims description 3
- 201000011549 stomach cancer Diseases 0.000 claims description 3
- 229940034785 sutent Drugs 0.000 claims description 3
- 201000000596 systemic lupus erythematosus Diseases 0.000 claims description 3
- 210000001550 testis Anatomy 0.000 claims description 3
- DPJRMOMPQZCRJU-UHFFFAOYSA-M thiamine hydrochloride Chemical compound Cl.[Cl-].CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N DPJRMOMPQZCRJU-UHFFFAOYSA-M 0.000 claims description 3
- 229940121358 tyrosine kinase inhibitor Drugs 0.000 claims description 3
- 239000005483 tyrosine kinase inhibitor Substances 0.000 claims description 3
- 150000004917 tyrosine kinase inhibitor derivatives Chemical class 0.000 claims description 3
- 241001529453 unidentified herpesvirus Species 0.000 claims description 3
- 201000005112 urinary bladder cancer Diseases 0.000 claims description 3
- 210000003462 vein Anatomy 0.000 claims description 3
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 claims description 3
- 229960004528 vincristine Drugs 0.000 claims description 3
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 claims description 3
- 235000019154 vitamin C Nutrition 0.000 claims description 3
- 239000011718 vitamin C Substances 0.000 claims description 3
- 208000010507 Adenocarcinoma of Lung Diseases 0.000 claims description 2
- 208000007860 Anus Neoplasms Diseases 0.000 claims description 2
- OBMZMSLWNNWEJA-XNCRXQDQSA-N C1=CC=2C(C[C@@H]3NC(=O)[C@@H](NC(=O)[C@H](NC(=O)N(CC#CCN(CCCC[C@H](NC(=O)[C@@H](CC4=CC=CC=C4)NC3=O)C(=O)N)CC=C)NC(=O)[C@@H](N)C)CC3=CNC4=C3C=CC=C4)C)=CNC=2C=C1 Chemical compound C1=CC=2C(C[C@@H]3NC(=O)[C@@H](NC(=O)[C@H](NC(=O)N(CC#CCN(CCCC[C@H](NC(=O)[C@@H](CC4=CC=CC=C4)NC3=O)C(=O)N)CC=C)NC(=O)[C@@H](N)C)CC3=CNC4=C3C=CC=C4)C)=CNC=2C=C1 OBMZMSLWNNWEJA-XNCRXQDQSA-N 0.000 claims description 2
- 108091007403 Cholesterol transporters Proteins 0.000 claims description 2
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 2
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 claims description 2
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 claims description 2
- DTHNMHAUYICORS-KTKZVXAJSA-N Glucagon-like peptide 1 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 DTHNMHAUYICORS-KTKZVXAJSA-N 0.000 claims description 2
- 206010019708 Hepatic steatosis Diseases 0.000 claims description 2
- 201000008450 Intracranial aneurysm Diseases 0.000 claims description 2
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 claims description 2
- 108060004795 Methyltransferase Proteins 0.000 claims description 2
- 102000016397 Methyltransferase Human genes 0.000 claims description 2
- 208000003250 Mixed connective tissue disease Diseases 0.000 claims description 2
- 241000187479 Mycobacterium tuberculosis Species 0.000 claims description 2
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 claims description 2
- 206010033799 Paralysis Diseases 0.000 claims description 2
- 206010034010 Parkinsonism Diseases 0.000 claims description 2
- 101710176384 Peptide 1 Proteins 0.000 claims description 2
- 206010038910 Retinitis Diseases 0.000 claims description 2
- 208000002495 Uterine Neoplasms Diseases 0.000 claims description 2
- RSPXHWRJTPGRHQ-UHFFFAOYSA-N [Pt].N.[Cl] Chemical compound [Pt].N.[Cl] RSPXHWRJTPGRHQ-UHFFFAOYSA-N 0.000 claims description 2
- 230000000843 anti-fungal effect Effects 0.000 claims description 2
- 229940121375 antifungal agent Drugs 0.000 claims description 2
- 201000011165 anus cancer Diseases 0.000 claims description 2
- 201000004982 autoimmune uveitis Diseases 0.000 claims description 2
- 208000019065 cervical carcinoma Diseases 0.000 claims description 2
- 208000029742 colonic neoplasm Diseases 0.000 claims description 2
- 210000004351 coronary vessel Anatomy 0.000 claims description 2
- 229960003668 docetaxel Drugs 0.000 claims description 2
- 230000012202 endocytosis Effects 0.000 claims description 2
- 229940125777 fusion inhibitor Drugs 0.000 claims description 2
- 210000002216 heart Anatomy 0.000 claims description 2
- 208000019622 heart disease Diseases 0.000 claims description 2
- 208000006454 hepatitis Diseases 0.000 claims description 2
- 231100000283 hepatitis Toxicity 0.000 claims description 2
- 230000000642 iatrogenic effect Effects 0.000 claims description 2
- 239000002955 immunomodulating agent Substances 0.000 claims description 2
- 229940121354 immunomodulator Drugs 0.000 claims description 2
- 230000002584 immunomodulator Effects 0.000 claims description 2
- 230000003834 intracellular effect Effects 0.000 claims description 2
- 208000019423 liver disease Diseases 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 229960000485 methotrexate Drugs 0.000 claims description 2
- 230000003071 parasitic effect Effects 0.000 claims description 2
- 230000001991 pathophysiological effect Effects 0.000 claims description 2
- 201000003068 rheumatic fever Diseases 0.000 claims description 2
- 239000003419 rna directed dna polymerase inhibitor Substances 0.000 claims description 2
- 206010046766 uterine cancer Diseases 0.000 claims description 2
- 208000019838 Blood disease Diseases 0.000 claims 1
- 101710198884 GATA-type zinc finger protein 1 Proteins 0.000 claims 1
- 102000051325 Glucagon Human genes 0.000 claims 1
- 108060003199 Glucagon Proteins 0.000 claims 1
- 102100040918 Pro-glucagon Human genes 0.000 claims 1
- 238000002725 brachytherapy Methods 0.000 claims 1
- 230000005754 cellular signaling Effects 0.000 claims 1
- 239000000470 constituent Substances 0.000 claims 1
- 230000009429 distress Effects 0.000 claims 1
- 230000005714 functional activity Effects 0.000 claims 1
- MASNOZXLGMXCHN-ZLPAWPGGSA-N glucagon Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 MASNOZXLGMXCHN-ZLPAWPGGSA-N 0.000 claims 1
- 229960004666 glucagon Drugs 0.000 claims 1
- 208000014951 hematologic disease Diseases 0.000 claims 1
- 208000018706 hematopoietic system disease Diseases 0.000 claims 1
- 206010022000 influenza Diseases 0.000 claims 1
- 244000005700 microbiome Species 0.000 claims 1
- 230000011278 mitosis Effects 0.000 claims 1
- 230000037361 pathway Effects 0.000 claims 1
- 208000019553 vascular disease Diseases 0.000 claims 1
- 239000000463 material Substances 0.000 abstract 1
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 42
- 235000012000 cholesterol Nutrition 0.000 description 19
- 238000011160 research Methods 0.000 description 12
- 208000024172 Cardiovascular disease Diseases 0.000 description 11
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 11
- 235000019197 fats Nutrition 0.000 description 11
- 102000005962 receptors Human genes 0.000 description 10
- 108020003175 receptors Proteins 0.000 description 10
- 210000001789 adipocyte Anatomy 0.000 description 9
- 230000006870 function Effects 0.000 description 9
- 239000002245 particle Substances 0.000 description 9
- 108010008951 Chemokine CXCL12 Proteins 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 8
- 102100021669 Stromal cell-derived factor 1 Human genes 0.000 description 8
- 230000012010 growth Effects 0.000 description 8
- 102100031650 C-X-C chemokine receptor type 4 Human genes 0.000 description 7
- 101000922348 Homo sapiens C-X-C chemokine receptor type 4 Proteins 0.000 description 7
- 235000019441 ethanol Nutrition 0.000 description 7
- 239000008103 glucose Substances 0.000 description 7
- 108010023302 HDL Cholesterol Proteins 0.000 description 6
- 102000004889 Interleukin-6 Human genes 0.000 description 6
- 108090001005 Interleukin-6 Proteins 0.000 description 6
- 108010028554 LDL Cholesterol Proteins 0.000 description 6
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 230000014509 gene expression Effects 0.000 description 6
- 229940100601 interleukin-6 Drugs 0.000 description 6
- 210000002540 macrophage Anatomy 0.000 description 6
- 230000007246 mechanism Effects 0.000 description 6
- 210000000496 pancreas Anatomy 0.000 description 6
- 150000003626 triacylglycerols Chemical class 0.000 description 6
- 208000037259 Amyloid Plaque Diseases 0.000 description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 5
- 230000008859 change Effects 0.000 description 5
- 230000006020 chronic inflammation Effects 0.000 description 5
- 238000011161 development Methods 0.000 description 5
- 230000018109 developmental process Effects 0.000 description 5
- 239000002609 medium Substances 0.000 description 5
- 108010007622 LDL Lipoproteins Proteins 0.000 description 4
- 102000007330 LDL Lipoproteins Human genes 0.000 description 4
- 102100033995 Long-chain-fatty-acid-CoA ligase 1 Human genes 0.000 description 4
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 4
- 230000001093 anti-cancer Effects 0.000 description 4
- 210000000170 cell membrane Anatomy 0.000 description 4
- 230000004069 differentiation Effects 0.000 description 4
- 238000002651 drug therapy Methods 0.000 description 4
- XMOCLSLCDHWDHP-IUODEOHRSA-N epi-Gallocatechin Chemical compound C1([C@H]2OC3=CC(O)=CC(O)=C3C[C@H]2O)=CC(O)=C(O)C(O)=C1 XMOCLSLCDHWDHP-IUODEOHRSA-N 0.000 description 4
- 235000011187 glycerol Nutrition 0.000 description 4
- 210000004185 liver Anatomy 0.000 description 4
- 229960003512 nicotinic acid Drugs 0.000 description 4
- 235000001968 nicotinic acid Nutrition 0.000 description 4
- 239000011664 nicotinic acid Substances 0.000 description 4
- 230000002018 overexpression Effects 0.000 description 4
- 238000007254 oxidation reaction Methods 0.000 description 4
- 230000001575 pathological effect Effects 0.000 description 4
- GCYXWQUSHADNBF-AAEALURTSA-N preproglucagon 78-108 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 GCYXWQUSHADNBF-AAEALURTSA-N 0.000 description 4
- 230000000770 proinflammatory effect Effects 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 230000028327 secretion Effects 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- 230000002195 synergetic effect Effects 0.000 description 4
- PFTAWBLQPZVEMU-DZGCQCFKSA-N (+)-catechin Chemical compound C1([C@H]2OC3=CC(O)=CC(O)=C3C[C@@H]2O)=CC=C(O)C(O)=C1 PFTAWBLQPZVEMU-DZGCQCFKSA-N 0.000 description 3
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 description 3
- 102000004127 Cytokines Human genes 0.000 description 3
- 108090000695 Cytokines Proteins 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- 108010010234 HDL Lipoproteins Proteins 0.000 description 3
- 102000015779 HDL Lipoproteins Human genes 0.000 description 3
- 241000711549 Hepacivirus C Species 0.000 description 3
- 101000799318 Homo sapiens Long-chain-fatty-acid-CoA ligase 1 Proteins 0.000 description 3
- 102000004895 Lipoproteins Human genes 0.000 description 3
- 108090001030 Lipoproteins Proteins 0.000 description 3
- 206010028851 Necrosis Diseases 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 239000003963 antioxidant agent Substances 0.000 description 3
- 230000003078 antioxidant effect Effects 0.000 description 3
- 235000006708 antioxidants Nutrition 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 210000004204 blood vessel Anatomy 0.000 description 3
- 208000035269 cancer or benign tumor Diseases 0.000 description 3
- 230000007547 defect Effects 0.000 description 3
- 235000005911 diet Nutrition 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 210000002950 fibroblast Anatomy 0.000 description 3
- 150000002402 hexoses Chemical class 0.000 description 3
- 208000026278 immune system disease Diseases 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 102000004311 liver X receptors Human genes 0.000 description 3
- 108090000865 liver X receptors Proteins 0.000 description 3
- 235000013372 meat Nutrition 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 230000017074 necrotic cell death Effects 0.000 description 3
- 230000003647 oxidation Effects 0.000 description 3
- 239000003614 peroxisome proliferator Substances 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 238000006116 polymerization reaction Methods 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 229960003471 retinol Drugs 0.000 description 3
- 235000020944 retinol Nutrition 0.000 description 3
- 239000011607 retinol Substances 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 150000003408 sphingolipids Chemical class 0.000 description 3
- 210000000130 stem cell Anatomy 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 231100000419 toxicity Toxicity 0.000 description 3
- 230000001988 toxicity Effects 0.000 description 3
- 230000032258 transport Effects 0.000 description 3
- 241000712461 unidentified influenza virus Species 0.000 description 3
- 230000029812 viral genome replication Effects 0.000 description 3
- LSHVYAFMTMFKBA-TZIWHRDSSA-N (-)-epicatechin-3-O-gallate Chemical compound O([C@@H]1CC2=C(O)C=C(C=C2O[C@@H]1C=1C=C(O)C(O)=CC=1)O)C(=O)C1=CC(O)=C(O)C(O)=C1 LSHVYAFMTMFKBA-TZIWHRDSSA-N 0.000 description 2
- 102100027831 14-3-3 protein theta Human genes 0.000 description 2
- LRYZPFWEZHSTHD-HEFFAWAOSA-O 2-[[(e,2s,3r)-2-formamido-3-hydroxyoctadec-4-enoxy]-hydroxyphosphoryl]oxyethyl-trimethylazanium Chemical class CCCCCCCCCCCCC\C=C\[C@@H](O)[C@@H](NC=O)COP(O)(=O)OCC[N+](C)(C)C LRYZPFWEZHSTHD-HEFFAWAOSA-O 0.000 description 2
- QSZQTGNYQLNKAQ-UHFFFAOYSA-N 2-hydroxy-3-phenylprop-2-enal Chemical compound O=CC(O)=CC1=CC=CC=C1 QSZQTGNYQLNKAQ-UHFFFAOYSA-N 0.000 description 2
- QCVGEOXPDFCNHA-UHFFFAOYSA-N 5,5-dimethyl-2,4-dioxo-1,3-oxazolidine-3-carboxamide Chemical compound CC1(C)OC(=O)N(C(N)=O)C1=O QCVGEOXPDFCNHA-UHFFFAOYSA-N 0.000 description 2
- 229920001817 Agar Polymers 0.000 description 2
- 102000013455 Amyloid beta-Peptides Human genes 0.000 description 2
- 108010090849 Amyloid beta-Peptides Proteins 0.000 description 2
- XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 description 2
- XUKUURHRXDUEBC-UHFFFAOYSA-N Atorvastatin Natural products C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CCC(O)CC(O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-UHFFFAOYSA-N 0.000 description 2
- 229940123208 Biguanide Drugs 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 241001115402 Ebolavirus Species 0.000 description 2
- 102000002322 Egg Proteins Human genes 0.000 description 2
- 108010000912 Egg Proteins Proteins 0.000 description 2
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 2
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 2
- 241000233866 Fungi Species 0.000 description 2
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 2
- 208000037357 HIV infectious disease Diseases 0.000 description 2
- 108010034145 Helminth Proteins Proteins 0.000 description 2
- 206010060378 Hyperinsulinaemia Diseases 0.000 description 2
- 208000031226 Hyperlipidaemia Diseases 0.000 description 2
- XMOCLSLCDHWDHP-UHFFFAOYSA-N L-Epigallocatechin Natural products OC1CC2=C(O)C=C(O)C=C2OC1C1=CC(O)=C(O)C(O)=C1 XMOCLSLCDHWDHP-UHFFFAOYSA-N 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 208000001145 Metabolic Syndrome Diseases 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 208000014060 Niemann-Pick disease Diseases 0.000 description 2
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 2
- 102000007399 Nuclear hormone receptor Human genes 0.000 description 2
- 108020005497 Nuclear hormone receptor Proteins 0.000 description 2
- YASAKCUCGLMORW-UHFFFAOYSA-N Rosiglitazone Chemical compound C=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O YASAKCUCGLMORW-UHFFFAOYSA-N 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 229930182558 Sterol Natural products 0.000 description 2
- 108091008874 T cell receptors Proteins 0.000 description 2
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 2
- 210000001744 T-lymphocyte Anatomy 0.000 description 2
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 125000002252 acyl group Chemical group 0.000 description 2
- 239000008272 agar Substances 0.000 description 2
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- 210000001367 artery Anatomy 0.000 description 2
- 230000036523 atherogenesis Effects 0.000 description 2
- 229960005370 atorvastatin Drugs 0.000 description 2
- 210000004323 caveolae Anatomy 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 239000005482 chemotactic factor Substances 0.000 description 2
- 229950001002 cianidanol Drugs 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 230000000378 dietary effect Effects 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- 235000015872 dietary supplement Nutrition 0.000 description 2
- 235000013399 edible fruits Nutrition 0.000 description 2
- 230000002526 effect on cardiovascular system Effects 0.000 description 2
- 235000014103 egg white Nutrition 0.000 description 2
- 210000000969 egg white Anatomy 0.000 description 2
- DZYNKLUGCOSVKS-UHFFFAOYSA-N epigallocatechin Natural products OC1Cc2cc(O)cc(O)c2OC1c3cc(O)c(O)c(O)c3 DZYNKLUGCOSVKS-UHFFFAOYSA-N 0.000 description 2
- 210000002744 extracellular matrix Anatomy 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 150000004665 fatty acids Chemical class 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 235000021588 free fatty acids Nutrition 0.000 description 2
- 208000021302 gastroesophageal reflux disease Diseases 0.000 description 2
- 239000003292 glue Substances 0.000 description 2
- 229930182470 glycoside Natural products 0.000 description 2
- 239000003102 growth factor Substances 0.000 description 2
- 210000004837 gut-associated lymphoid tissue Anatomy 0.000 description 2
- 244000000013 helminth Species 0.000 description 2
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 2
- 201000001421 hyperglycemia Diseases 0.000 description 2
- 230000003451 hyperinsulinaemic effect Effects 0.000 description 2
- 201000008980 hyperinsulinism Diseases 0.000 description 2
- 230000002218 hypoglycaemic effect Effects 0.000 description 2
- 230000028993 immune response Effects 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 208000032839 leukemia Diseases 0.000 description 2
- 150000002617 leukotrienes Chemical class 0.000 description 2
- 210000004698 lymphocyte Anatomy 0.000 description 2
- 230000002101 lytic effect Effects 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
- 230000004060 metabolic process Effects 0.000 description 2
- 210000001616 monocyte Anatomy 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- 239000002547 new drug Substances 0.000 description 2
- 108020004017 nuclear receptors Proteins 0.000 description 2
- 235000016709 nutrition Nutrition 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- 230000008521 reorganization Effects 0.000 description 2
- 230000011506 response to oxidative stress Effects 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 150000003432 sterols Chemical class 0.000 description 2
- 235000003702 sterols Nutrition 0.000 description 2
- 239000013589 supplement Substances 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- XMOCLSLCDHWDHP-DOMZBBRYSA-N (-)-gallocatechin Chemical compound C1([C@@H]2OC3=CC(O)=CC(O)=C3C[C@H]2O)=CC(O)=C(O)C(O)=C1 XMOCLSLCDHWDHP-DOMZBBRYSA-N 0.000 description 1
- RSVQBAQLVQBVQO-UHFFFAOYSA-N (2-hydroxyphenyl) 3,4,5-trihydroxybenzoate Chemical compound OC1=C(O)C(O)=CC(C(=O)OC=2C(=CC=CC=2)O)=C1 RSVQBAQLVQBVQO-UHFFFAOYSA-N 0.000 description 1
- KJPRLNWUNMBNBZ-QPJJXVBHSA-N (E)-cinnamaldehyde Chemical compound O=C\C=C\C1=CC=CC=C1 KJPRLNWUNMBNBZ-QPJJXVBHSA-N 0.000 description 1
- 239000001707 (E,7R,11R)-3,7,11,15-tetramethylhexadec-2-en-1-ol Substances 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- HOMYIYLRRDTKAA-UHFFFAOYSA-N 2-hydroxy-N-[3-hydroxy-1-[3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoctadeca-4,8-dien-2-yl]hexadecanamide Chemical compound CCCCCCCCCCCCCCC(O)C(=O)NC(C(O)C=CCCC=CCCCCCCCCC)COC1OC(CO)C(O)C(O)C1O HOMYIYLRRDTKAA-UHFFFAOYSA-N 0.000 description 1
- QHMQAWNNHVPBQU-UHFFFAOYSA-N 3-(2-hydroxy-3-methylphenyl)-1-phenylprop-2-en-1-one Chemical compound CC1=CC=CC(C=CC(=O)C=2C=CC=CC=2)=C1O QHMQAWNNHVPBQU-UHFFFAOYSA-N 0.000 description 1
- HVCOBJNICQPDBP-UHFFFAOYSA-N 3-[3-[3,5-dihydroxy-6-methyl-4-(3,4,5-trihydroxy-6-methyloxan-2-yl)oxyoxan-2-yl]oxydecanoyloxy]decanoic acid;hydrate Chemical compound O.OC1C(OC(CC(=O)OC(CCCCCCC)CC(O)=O)CCCCCCC)OC(C)C(O)C1OC1C(O)C(O)C(O)C(C)O1 HVCOBJNICQPDBP-UHFFFAOYSA-N 0.000 description 1
- TVZGACDUOSZQKY-LBPRGKRZSA-N 4-aminofolic acid Chemical compound C1=NC2=NC(N)=NC(N)=C2N=C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 TVZGACDUOSZQKY-LBPRGKRZSA-N 0.000 description 1
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- 101150092476 ABCA1 gene Proteins 0.000 description 1
- 102000015936 AP-1 transcription factor Human genes 0.000 description 1
- 108050004195 AP-1 transcription factor Proteins 0.000 description 1
- 108700005241 ATP Binding Cassette Transporter 1 Proteins 0.000 description 1
- 102000005416 ATP-Binding Cassette Transporters Human genes 0.000 description 1
- 108010006533 ATP-Binding Cassette Transporters Proteins 0.000 description 1
- 102100022594 ATP-binding cassette sub-family G member 1 Human genes 0.000 description 1
- 244000235603 Acacia catechu Species 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 102100033715 Apolipoprotein A-I Human genes 0.000 description 1
- 101710095342 Apolipoprotein B Proteins 0.000 description 1
- 102100040202 Apolipoprotein B-100 Human genes 0.000 description 1
- 235000006226 Areca catechu Nutrition 0.000 description 1
- 200000000007 Arterial disease Diseases 0.000 description 1
- 241000193830 Bacillus <bacterium> Species 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 102100035875 C-C chemokine receptor type 5 Human genes 0.000 description 1
- 101710149870 C-C chemokine receptor type 5 Proteins 0.000 description 1
- 101710155857 C-C motif chemokine 2 Proteins 0.000 description 1
- 238000011740 C57BL/6 mouse Methods 0.000 description 1
- 102000009122 CCAAT-Enhancer-Binding Proteins Human genes 0.000 description 1
- 108010048401 CCAAT-Enhancer-Binding Proteins Proteins 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 108050000084 Caveolin Proteins 0.000 description 1
- 102000009193 Caveolin Human genes 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 244000163122 Curcuma domestica Species 0.000 description 1
- 235000003392 Curcuma domestica Nutrition 0.000 description 1
- 102100028717 Cytosolic 5'-nucleotidase 3A Human genes 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 229940126190 DNA methyltransferase inhibitor Drugs 0.000 description 1
- QSJXEFYPDANLFS-UHFFFAOYSA-N Diacetyl Chemical group CC(=O)C(C)=O QSJXEFYPDANLFS-UHFFFAOYSA-N 0.000 description 1
- 108090000194 Dipeptidyl-peptidases and tripeptidyl-peptidases Proteins 0.000 description 1
- 102000003779 Dipeptidyl-peptidases and tripeptidyl-peptidases Human genes 0.000 description 1
- LSHVYAFMTMFKBA-UHFFFAOYSA-N ECG Natural products C=1C=C(O)C(O)=CC=1C1OC2=CC(O)=CC(O)=C2CC1OC(=O)C1=CC(O)=C(O)C(O)=C1 LSHVYAFMTMFKBA-UHFFFAOYSA-N 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 241000588722 Escherichia Species 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- 102400000322 Glucagon-like peptide 1 Human genes 0.000 description 1
- 101800000224 Glucagon-like peptide 1 Proteins 0.000 description 1
- 208000002705 Glucose Intolerance Diseases 0.000 description 1
- 206010018429 Glucose tolerance impaired Diseases 0.000 description 1
- 102000017011 Glycated Hemoglobin A Human genes 0.000 description 1
- 108010014663 Glycated Hemoglobin A Proteins 0.000 description 1
- 229930186217 Glycolipid Natural products 0.000 description 1
- 206010018473 Glycosuria Diseases 0.000 description 1
- 229920002907 Guar gum Polymers 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 229920000569 Gum karaya Polymers 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- 102100021866 Hepatocyte growth factor Human genes 0.000 description 1
- SQUHHTBVTRBESD-UHFFFAOYSA-N Hexa-Ac-myo-Inositol Natural products CC(=O)OC1C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C1OC(C)=O SQUHHTBVTRBESD-UHFFFAOYSA-N 0.000 description 1
- 101000733802 Homo sapiens Apolipoprotein A-I Proteins 0.000 description 1
- 101000908391 Homo sapiens Dipeptidyl peptidase 4 Proteins 0.000 description 1
- 101000896414 Homo sapiens Nuclear nucleic acid-binding protein C1D Proteins 0.000 description 1
- 101001043564 Homo sapiens Prolow-density lipoprotein receptor-related protein 1 Proteins 0.000 description 1
- 208000035150 Hypercholesterolemia Diseases 0.000 description 1
- 208000013016 Hypoglycemia Diseases 0.000 description 1
- 206010021024 Hypolipidaemia Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 208000007746 Immunologic Deficiency Syndromes Diseases 0.000 description 1
- 206010061216 Infarction Diseases 0.000 description 1
- 102000004890 Interleukin-8 Human genes 0.000 description 1
- 108090001007 Interleukin-8 Proteins 0.000 description 1
- 208000005016 Intestinal Neoplasms Diseases 0.000 description 1
- 239000005551 L01XE03 - Erlotinib Substances 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 239000000232 Lipid Bilayer Substances 0.000 description 1
- 206010049287 Lipodystrophy acquired Diseases 0.000 description 1
- 108010033266 Lipoprotein(a) Proteins 0.000 description 1
- 102000057248 Lipoprotein(a) Human genes 0.000 description 1
- 241000219745 Lupinus Species 0.000 description 1
- 108010090314 Member 1 Subfamily G ATP Binding Cassette Transporter Proteins 0.000 description 1
- 102000003939 Membrane transport proteins Human genes 0.000 description 1
- 108090000301 Membrane transport proteins Proteins 0.000 description 1
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 1
- 102100021713 Nuclear nucleic acid-binding protein C1D Human genes 0.000 description 1
- NPGIHFRTRXVWOY-UHFFFAOYSA-N Oil red O Chemical compound Cc1ccc(C)c(c1)N=Nc1cc(C)c(cc1C)N=Nc1c(O)ccc2ccccc12 NPGIHFRTRXVWOY-UHFFFAOYSA-N 0.000 description 1
- 235000019082 Osmanthus Nutrition 0.000 description 1
- 241000333181 Osmanthus Species 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 102000023984 PPAR alpha Human genes 0.000 description 1
- 108010028924 PPAR alpha Proteins 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 102000003992 Peroxidases Human genes 0.000 description 1
- 102000003728 Peroxisome Proliferator-Activated Receptors Human genes 0.000 description 1
- 108090000029 Peroxisome Proliferator-Activated Receptors Proteins 0.000 description 1
- 244000046052 Phaseolus vulgaris Species 0.000 description 1
- 235000010627 Phaseolus vulgaris Nutrition 0.000 description 1
- 102100033616 Phospholipid-transporting ATPase ABCA1 Human genes 0.000 description 1
- BLUHKGOSFDHHGX-UHFFFAOYSA-N Phytol Natural products CC(C)CCCC(C)CCCC(C)CCCC(C)C=CO BLUHKGOSFDHHGX-UHFFFAOYSA-N 0.000 description 1
- 241000223960 Plasmodium falciparum Species 0.000 description 1
- 108010007568 Protamines Proteins 0.000 description 1
- 102000007327 Protamines Human genes 0.000 description 1
- 102000001253 Protein Kinase Human genes 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 208000025747 Rheumatic disease Diseases 0.000 description 1
- 108010026951 Short-Acting Insulin Proteins 0.000 description 1
- 229940123958 Short-acting insulin Drugs 0.000 description 1
- 229940123518 Sodium/glucose cotransporter 2 inhibitor Drugs 0.000 description 1
- 241000786103 Steatomys pratensis Species 0.000 description 1
- 241000934878 Sterculia Species 0.000 description 1
- 102000003673 Symporters Human genes 0.000 description 1
- 108090000088 Symporters Proteins 0.000 description 1
- HNZBNQYXWOLKBA-UHFFFAOYSA-N Tetrahydrofarnesol Natural products CC(C)CCCC(C)CCCC(C)=CCO HNZBNQYXWOLKBA-UHFFFAOYSA-N 0.000 description 1
- 101000972444 Thermus thermophilus (strain ATCC 27634 / DSM 579 / HB8) Long-chain-fatty-acid-CoA ligase Proteins 0.000 description 1
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
- 102100040247 Tumor necrosis factor Human genes 0.000 description 1
- AXMVYSVVTMKQSL-UHFFFAOYSA-N UNPD142122 Natural products OC1=CC=C(C=CC=O)C=C1O AXMVYSVVTMKQSL-UHFFFAOYSA-N 0.000 description 1
- 206010046851 Uveitis Diseases 0.000 description 1
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 1
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 1
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 1
- 102100026383 Vasopressin-neurophysin 2-copeptin Human genes 0.000 description 1
- 235000009754 Vitis X bourquina Nutrition 0.000 description 1
- 235000012333 Vitis X labruscana Nutrition 0.000 description 1
- 240000006365 Vitis vinifera Species 0.000 description 1
- 235000014787 Vitis vinifera Nutrition 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 210000003486 adipose tissue brown Anatomy 0.000 description 1
- 230000011759 adipose tissue development Effects 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- BOTWFXYSPFMFNR-OALUTQOASA-N all-rac-phytol Natural products CC(C)CCC[C@H](C)CCC[C@H](C)CCCC(C)=CCO BOTWFXYSPFMFNR-OALUTQOASA-N 0.000 description 1
- 229960003896 aminopterin Drugs 0.000 description 1
- BSJGASKRWFKGMV-UHFFFAOYSA-L ammonia dichloroplatinum(2+) Chemical compound N.N.Cl[Pt+2]Cl BSJGASKRWFKGMV-UHFFFAOYSA-L 0.000 description 1
- 239000010775 animal oil Substances 0.000 description 1
- 229940127003 anti-diabetic drug Drugs 0.000 description 1
- 230000003064 anti-oxidating effect Effects 0.000 description 1
- 238000011319 anticancer therapy Methods 0.000 description 1
- 238000011225 antiretroviral therapy Methods 0.000 description 1
- 210000000436 anus Anatomy 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 230000008952 bacterial invasion Effects 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- 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 1
- 210000000941 bile Anatomy 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 239000000090 biomarker Substances 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 230000036770 blood supply Effects 0.000 description 1
- 210000000746 body region Anatomy 0.000 description 1
- 210000000133 brain stem Anatomy 0.000 description 1
- 239000007963 capsule composition Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 210000002318 cardia Anatomy 0.000 description 1
- 230000010036 cardiovascular benefit Effects 0.000 description 1
- 210000000748 cardiovascular system Anatomy 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000007541 cellular toxicity Effects 0.000 description 1
- 230000003399 chemotactic effect Effects 0.000 description 1
- KJPRLNWUNMBNBZ-UHFFFAOYSA-N cinnamic aldehyde Natural products O=CC=CC1=CC=CC=C1 KJPRLNWUNMBNBZ-UHFFFAOYSA-N 0.000 description 1
- 229940117916 cinnamic aldehyde Drugs 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 230000019771 cognition Effects 0.000 description 1
- 230000001149 cognitive effect Effects 0.000 description 1
- 238000004891 communication Methods 0.000 description 1
- 230000008094 contradictory effect Effects 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 229940099112 cornstarch Drugs 0.000 description 1
- 235000003373 curcuma longa Nutrition 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- CYQFCXCEBYINGO-IAGOWNOFSA-N delta1-THC Chemical compound C1=C(C)CC[C@H]2C(C)(C)OC3=CC(CCCCC)=CC(O)=C3[C@@H]21 CYQFCXCEBYINGO-IAGOWNOFSA-N 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 201000010064 diabetes insipidus Diseases 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 1
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000003968 dna methyltransferase inhibitor Substances 0.000 description 1
- 201000006549 dyspepsia Diseases 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- AAKJLRGGTJKAMG-UHFFFAOYSA-N erlotinib Chemical compound C=12C=C(OCCOC)C(OCCOC)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 AAKJLRGGTJKAMG-UHFFFAOYSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000014818 extracellular matrix organization Effects 0.000 description 1
- 201000005577 familial hyperlipidemia Diseases 0.000 description 1
- 210000003746 feather Anatomy 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 229940125753 fibrate Drugs 0.000 description 1
- 210000000232 gallbladder Anatomy 0.000 description 1
- 230000007661 gastrointestinal function Effects 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 208000004104 gestational diabetes Diseases 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 230000004153 glucose metabolism Effects 0.000 description 1
- 230000002641 glycemic effect Effects 0.000 description 1
- 150000002338 glycosides Chemical class 0.000 description 1
- 150000002339 glycosphingolipids Chemical class 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 239000000665 guar gum Substances 0.000 description 1
- 235000010417 guar gum Nutrition 0.000 description 1
- 229960002154 guar gum Drugs 0.000 description 1
- 229920000591 gum Polymers 0.000 description 1
- 208000014829 head and neck neoplasm Diseases 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 208000024798 heartburn Diseases 0.000 description 1
- 210000002443 helper t lymphocyte Anatomy 0.000 description 1
- 210000003494 hepatocyte Anatomy 0.000 description 1
- 210000003630 histaminocyte Anatomy 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- MGXWVYUBJRZYPE-YUGYIWNOSA-N incretin Chemical class C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(N)=O)C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1C=CC(O)=CC=1)[C@@H](C)O)[C@@H](C)CC)C1=CC=C(O)C=C1 MGXWVYUBJRZYPE-YUGYIWNOSA-N 0.000 description 1
- 239000000859 incretin Substances 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000007574 infarction Effects 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 229960000367 inositol Drugs 0.000 description 1
- CDAISMWEOUEBRE-GPIVLXJGSA-N inositol Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](O)[C@@H]1O CDAISMWEOUEBRE-GPIVLXJGSA-N 0.000 description 1
- 239000004026 insulin derivative Substances 0.000 description 1
- 230000003914 insulin secretion Effects 0.000 description 1
- 229940096397 interleukin-8 Drugs 0.000 description 1
- XKTZWUACRZHVAN-VADRZIEHSA-N interleukin-8 Chemical compound C([C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@@H](NC(C)=O)CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CCSC)C(=O)N1[C@H](CCC1)C(=O)N1[C@H](CCC1)C(=O)N[C@@H](C)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC=1C=CC(O)=CC=1)C(=O)N[C@H](CO)C(=O)N1[C@H](CCC1)C(N)=O)C1=CC=CC=C1 XKTZWUACRZHVAN-VADRZIEHSA-N 0.000 description 1
- 201000002313 intestinal cancer Diseases 0.000 description 1
- 210000001596 intra-abdominal fat Anatomy 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 235000010494 karaya gum Nutrition 0.000 description 1
- 239000000231 karaya gum Substances 0.000 description 1
- 229940039371 karaya gum Drugs 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 210000002429 large intestine Anatomy 0.000 description 1
- 208000006132 lipodystrophy Diseases 0.000 description 1
- 230000004130 lipolysis Effects 0.000 description 1
- 108010022197 lipoprotein cholesterol Proteins 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 210000003712 lysosome Anatomy 0.000 description 1
- 230000001868 lysosomic effect Effects 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 208000026037 malignant tumor of neck Diseases 0.000 description 1
- 210000005075 mammary gland Anatomy 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 238000010197 meta-analysis Methods 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000001394 metastastic effect Effects 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 244000000010 microbial pathogen Species 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 210000000274 microglia Anatomy 0.000 description 1
- 230000000394 mitotic effect Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000003607 modifier Substances 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 229940031815 mycocide Drugs 0.000 description 1
- 210000004165 myocardium Anatomy 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 210000002682 neurofibrillary tangle Anatomy 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 229940042402 non-nucleoside reverse transcriptase inhibitor Drugs 0.000 description 1
- 239000002726 nonnucleoside reverse transcriptase inhibitor Substances 0.000 description 1
- 235000021590 normal diet Nutrition 0.000 description 1
- 238000011330 nucleic acid test Methods 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 235000020660 omega-3 fatty acid Nutrition 0.000 description 1
- 229940012843 omega-3 fatty acid Drugs 0.000 description 1
- 229940127017 oral antidiabetic Drugs 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 238000009980 pad dyeing Methods 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000000149 penetrating effect Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- 210000002824 peroxisome Anatomy 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- BOTWFXYSPFMFNR-PYDDKJGSSA-N phytol Chemical compound CC(C)CCC[C@@H](C)CCC[C@@H](C)CCC\C(C)=C\CO BOTWFXYSPFMFNR-PYDDKJGSSA-N 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 210000002381 plasma Anatomy 0.000 description 1
- 239000011505 plaster Substances 0.000 description 1
- 210000002706 plastid Anatomy 0.000 description 1
- 230000007096 poisonous effect Effects 0.000 description 1
- 229920001296 polysiloxane Polymers 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 229940116317 potato starch Drugs 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 235000013772 propylene glycol Nutrition 0.000 description 1
- 229940048914 protamine Drugs 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- 235000021251 pulses Nutrition 0.000 description 1
- 238000012797 qualification Methods 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 208000007278 renal glycosuria Diseases 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000010839 reverse transcription Methods 0.000 description 1
- 230000000552 rheumatic effect Effects 0.000 description 1
- 229960004586 rosiglitazone Drugs 0.000 description 1
- CDAISMWEOUEBRE-UHFFFAOYSA-N scyllo-inosotol Natural products OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 description 1
- 230000009863 secondary prevention Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 229940032147 starch Drugs 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical class OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 description 1
- 230000001502 supplementing effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000008718 systemic inflammatory response Effects 0.000 description 1
- 229940120982 tarceva Drugs 0.000 description 1
- 210000003684 theca cell Anatomy 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 238000012549 training Methods 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 102000035160 transmembrane proteins Human genes 0.000 description 1
- 108091005703 transmembrane proteins Proteins 0.000 description 1
- 201000008827 tuberculosis Diseases 0.000 description 1
- 230000005748 tumor development Effects 0.000 description 1
- 102000003390 tumor necrosis factor Human genes 0.000 description 1
- 235000013976 turmeric Nutrition 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 210000002845 virion Anatomy 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/575—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
-
- 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
- A61K31/01—Hydrocarbons
- A61K31/015—Hydrocarbons carbocyclic
-
- 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
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
-
- 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
- A61K31/11—Aldehydes
-
- 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
- A61K31/12—Ketones
-
- 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
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
- A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
-
- 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
- A61K31/366—Lactones having six-membered rings, e.g. delta-lactones
-
- 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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
-
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Cardiology (AREA)
- Virology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Oncology (AREA)
- Heart & Thoracic Surgery (AREA)
- Communicable Diseases (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medical Preparation Storing Or Oral Administration Devices (AREA)
Abstract
本发明涉及一种药物成分,其特征在于它包括香芹烯、羽扇豆醇和肉桂醛、表儿茶酸、肉桂中的一种浓缩物MHCP、β‑谷甾醇、姜黄色素等中选择的药物有效成分以及它们的混合物作为有效成分。它适用于预防和治疗感染物质引起的肥胖、糖尿病、血脂异常、感染以及它们的并发症并且可以用于侵入性癌症尤其是脂肪组织相关的癌症的预防和治疗。
Description
技术领域
本发明涉及一种可以用作医药的药物成分,尤其是用于病理学、癌症、尤其是和脂肪组织相关的癌症、神经变性疾病以及感染类疾病本案中指HIV感染相关的或并发的糖尿病和血脂异常的治疗。
现有技术。
肥胖、代谢综合征和糖尿病的流行和动脉粥样硬化以及心脏血管疾病(心脏,血管)或(颈部、腿部和心脏部位等的)动脉疾病的早发直接相关。
尽管动脉粥样硬化的发病原因明显有多个方面,血脂异常是糖尿病中心脏血管疾病的一个重要的预警。在2型糖尿病中,血脂异常导致了脂蛋白量的和质的异常(其表现为低密度脂蛋白颗粒(LDL颗粒)很小且稠、胆固醇增加,尤其具有容易导致动脉粥样硬化、易氧化以及容易残留在动脉壁上的特质),甘油三酯(TG)轻微增加,高密度脂蛋白胆固醇(HDL-c)量降低。在1型糖尿病的血脂异常中,脂蛋白量的异常比较少见(除了有肾脏障碍的1型糖尿病)。但是,脂蛋白的质的变化很常见,通常会导致低密度脂蛋白颗粒(LDL颗粒)的动脉粥样硬化形成增加,减少高密度脂蛋白颗粒(HDL颗粒)对抗动脉粥样硬化形成的能力。
大部分血脂异常的治疗数据是从2型糖尿病病人身上获得的,其中血脂异常和抗胰岛素性以及血胰岛素过多等高度相关。另外一方面,1型糖尿病人中,心脏血管疾病风险增加不应被忽视,这些病人也应得到血脂异常的治疗。
另外,HIV阳性接受抗逆转录治疗的病人,这种治疗的副作用很多,比如糖尿病、脂肪代谢障碍、甘油三酯和/或胆固醇的异常升高为特征的血脂异常等。这些感染的病人患动脉粥样硬化的风险也增加了,这是由于ABC转运蛋白中的负调节因子病毒蛋白质的副作用造成的,这种ABC转运蛋白涉及到细胞胆固醇的流出。这些病人的细胞表型会变化。这些细胞(原始的干细胞、脂肪细胞、胶质细胞、各种单核细胞、巨噬细胞以及CD4-T淋巴细胞等)变的更加活跃,进一步存储脂类小滴,和病毒粒子之间的融合力增加,成为了病毒的存储库,抗逆转录病毒无法进入。在这些细胞中增加脂质的话,尤其是在细胞膜水平增加,会加速干扰和病毒复制。这些细胞的细胞膜的脂膜筏在其中起主要作用。
这些是细胞膜的微型领地,也称为脂膜筏,其中包括密集排布的脂类(鞘糖脂和/或鞘磷脂以及胆固醇)和蛋白质(糖磷脂酰肌醇锚定蛋白、胆固醇相关的蛋白质、跨膜蛋白双乙酰化的SRC家族蛋白激酶)。脂类是蛋白质膜的溶解剂。HIV病毒在进入的时候以及病毒粒子萌芽的时候会和这些脂膜筏产生反应,导致某些脂类的选择性结合进入了病毒包膜,使所述病毒更加坚固。有些鞘糖脂甚至对HIV病毒有辅助因子或共受体的作用。此外,半乳糖基神经酰胺有时对有些HIV靶细胞也会产生受体的作用。
在一些无包被病毒或包膜病毒比如麻疹病毒和流感病毒等中也观察到了这种利用脂膜筏的进入机制。大肠杆菌细菌就是通过这种途径进入肥大细胞的。有些病原体(朊病毒蛋白质、恶性疟原虫)使用细胞膜穴样内陷。细胞膜穴样内陷代表了这些微型领地中的一个副类目。其中包含连接到胆固醇和鞘磷脂的蛋白质和小窝蛋白。
此外,肠相关淋巴组织(GALT),HIV病毒的主要的存储地,包括80%-90%的人体淋巴细胞,其中最主要是记忆细胞和活性CD4+辅助性T细胞 CCR5,HIV-1的首选目标。这是许多和感染这个病毒相关的免疫异常和结构问题的根源。这种由于CD4和T淋巴细胞,尤其是涉及到粘膜免疫力和渗透性的Th17淋巴细胞的过早且大量消耗,导致:细菌从肠道转移到血液循环中,代谢紊乱,系统性免疫超活化,慢性炎症以及病毒复制的翻倍。由此,导致疾病的演进、非传染性合并症比如心脏血管疾病、骨质疏松和艾滋病有关或无关的癌症、神经认知方面的功能障碍等的迅速发展。此外,研究经常发现脂肪组织距离侵入性癌症尤其是乳腺癌和前列腺癌很近。成熟的脂肪细胞和癌症相关,会在肿瘤演进、转移力的获得以及通过分泌发炎细胞因子、细胞外基质的蛋白质以及改编基质细胞衍生因子-1(SDF-1)等抵抗化学毒素治疗。有些肿瘤细胞超表达鞘糖脂,包括酰基鞘鞍醇三己糖(Gb3)、趋化因子受体CXCR4蛋白质,其也是一种X4病毒趋化共受体。趋化因子受体CXCR4或SDF-1轴系统的产生会在抑制免疫微环境的产生和新的血液供应的形成方面起到基础作用。在肥胖条件下,这种脂肪细胞、脂类负荷细胞以及肿瘤细胞之间的动态反应会翻倍,这解释了这样的癌症病人的预期比较差的原因。
另外,血脂异常还是促进神经变性疾病比如阿兹海默综合征、血管性痴呆等疾病的因素。实际上,在阿兹海默综合征中,我们观察到了病人的大脑、老年斑中包含一种特定的蛋白质Tau蛋白的缠结为特征的淀粉样肽增加、神经纤维缠结。这些老年斑导致多种认知缺陷,而这些认知缺陷仅可通过大脑胆固醇代谢部分修正。这种β淀粉样蛋白也牵扯到低密度脂蛋白胆固醇受体包膜表达的减少。这种机制可能和氧化应缴反应有关,与观察到的胰岛素受体的包膜表达的减少类似,可以解释阿兹海默综合征和胰岛素抵抗之间的关系。另外,这些老年斑周围的免疫细胞(巨噬细胞和小胶质细胞等)的防御导致的全身炎症反应也导致了阿兹海默综合征的演进。
因此,在许多疾病比如神经变性疾病、糖尿病、肾脏疾病、癌症和艾滋中发生的血脂异常和慢性炎症的管理中,卫生饮食管理必不可少,但是仅仅通过饮食管理是不足的,必须以药物治疗为补充。
降低脂类的疗法作为减少糖尿病人、HIV病人以及血脂异常病人的心脏血管疾病风险的潜在武器产生了。这些治疗方法包括口服和/或注射抗糖尿病的介质和/或降低脂类的介质混合。这种混合搭配方法根据病人对这种疗法的反应的不同而不同。
口服的抗糖尿病药物包括:双胍类,可以提高肝脏、肌肉或脂肪对于胰岛素的敏感度。然而,它们的行为需要内生或外生的胰岛素的参与;磺酰脲类和格列奈类药物药物,它们通过胰脏的β细胞刺激胰岛素的分泌。它们的有效性取决于胰脏残存的分泌胰岛素的能力;α-葡萄糖苷酶抑制剂,它们可以减缓消化的食物中糖分从肠道到血液的传达。它不会造成血糖过低;肠促胰岛素包括胰高血糖素样肽-1(GLP-1),这是机体在用餐开始时释放的物质,刺激胰岛素的分泌。药理学中它是通过注射胰高血糖素样肽-1(GLP-1)或通过二肽基肽酶-4(DPP4酶)抑制剂或列汀类药物由机体减少其退化;钠-葡萄糖协同转运蛋白2抑制剂(SGLT2抑制剂)去除尿中的葡萄糖。
可以注射的形式包括胰高血糖素样肽-1(GLP-1)类似物、胰岛素(长效胰岛素、中效胰岛素和短效胰岛素的混合物)。在降脂类剂中,我们发现:最常用的抑制素在降低血液中的胆固醇水平方面比较有效,尤其是低密度脂蛋白胆固醇水平。它们减少了由于动脉变窄或闭塞造成的疾病的发作或复发的风险,这些疾病包括:心肌梗死、周边动脉疾病、中风发作等。
贝特类药物是通过激活过氧化物酶体增殖物活化受体PPARα作用的。他们减少了血液中的甘油三酯水平增加了高密度脂蛋白胆固醇“好的胆固醇”。它们在减少心脏血管疾病的发作风险方面的作用比较平庸;依泽替米贝选择性地抑制了肠道对于胆固醇和相关的植物甾醇类的吸收;尼克酸减少了脂肪组织的自由脂肪酸的释放,可以降低低密度脂蛋白胆固醇、总胆固醇(CT)、极低密度脂蛋白胆固醇、载脂蛋白B、甘油三酯、脂蛋白a的离子水平以及增加高密度脂蛋白胆固醇以及APOA1蛋白,所有上述因素都和心脏血管疾病风险下降相关;ω−3脂肪酸是人体发育以及正常运转必须的脂肪酸,但是人体不能自己生产。
但是最近的文献带来了抑制素对心脏血管并发症风险以及破坏血糖控制风险等方面的影响的问题。实际上,在最近的治疗新目标(TNT)研究中,在研究结束后服用80mg阿托伐他汀的糖尿病人比只接受10mg阿托伐他汀的非糖尿病人发生心脏血管疾病更多。在糖尿病并发症血脂异常研究(ACCORD研究)中也强调了这种剩余的风险,尤其是次级预防以及有导致动脉粥样硬化的血脂异常的病人(其特征在于甘油三酯增加,高密度脂蛋白胆固醇低)。另外,研究(PROVE-IT研究和JUPITER研究)显示除了葡萄糖不耐受的任何迹象,有些进行抑制素疗法的人感染了糖尿病。对此的元分析确认了糖尿病的风险增加了9%。更重要的是,绝经期妇女中本风险增加到了近50%。尽管有这一结论,现在也不能弃用抑制素,因为他们对心脏血管的好处使我们无法质疑它的益处/风险比例。而更加矛盾的是,由于抑制素治疗中残留的心脏血管风险,目前趋势是加强治疗。
关于依泽替米贝、非诺贝特以及烟酸,除了它们与抑制素的联系以外,其降低血脂的生物效果已经得到证实,而其对于葡萄糖平衡方面的数据有限。
此外,在糖尿病和肥胖病人中,白细胞、循环单核细胞、巨噬细胞以及成熟的脂肪细胞中具有炎症特征。它们对于脂肪组织和其它器官有影响,因为他们对于肝脏、胰脏、肌肉、大脑以及心脏血管系统紊乱有促进作用。这种炎症通过生物学的生物标记如肿瘤坏死细胞α、白介素6、脂肪细胞因子、长链脂酰辅酶A合成酶1(ACSL1)以及白三烯的超表达得到了证实。
肿瘤坏死细胞α在肥胖相关的胰岛素抵抗的发展方面起了一定作用。它还减少了肝细胞和骨骼肌肉中的脂肪酸的氧化。它还通过作用于CCAAT 增强子结合蛋白(C/BBP)和过氧化物酶体增殖物活化受体(PPAR)抑制脂肪细胞分化。它还增加了脂类分解作用。
白介素6(IL-6)在引起和加速慢性炎症方面起了很重要的作用。它还和肥胖相关的胰岛素抵抗有关。这些等离子水平的增加和许多可以引起糖尿病人微脉管综合征发展的变量(空腹血糖水平、低密度脂蛋白胆固醇、总胆固醇以及身体质量指数)有关。
另外,过氧化物酶体增殖物活化受体y(PPARy)减弱了肿瘤坏死因子a以及白介素-6(IL-6)在脂肪组织中的作用,从而提高胰岛素敏感度。一般情况下,包括各种过氧化物酶体增殖物活化受体、肝脏X受体以及视黄醇X受体等核受体通过激活膜转运蛋白1(ABCA1)以及三磷酸腺苷结合盒转运体G1(ABCG1)胆固醇转运体的转录调节不同类型的细胞中流出的胆固醇。它们还增加了溶酶体胆固醇输送中涉及的尼曼匹克病C型1例(NPC1)和尼曼匹克病C型2例(NPC2)蛋白质的表达。它们还通过转录抑制机制下调了一些炎症基因(核因子活化B细胞κ轻链增强子NF-KappaB,STAT信号通路以及AP-1转录因子)。
几乎所有的脂肪因子都和脂肪质量增加相关的炎症有关,在胰岛素抵抗的发展中起了一定的作用。它们的高血药浓度也表明它们在许多肥胖相关的并发症的产生和发展中起了重要的作用(包括糖尿病和心脏血管疾病)。还应注意到糖尿病动脉粥样硬化和长链脂酰辅酶A合成酶1(ACSL1)的过度产生有关。
肥胖的人的脂肪细胞中产生的白三烯促进了炎症和胰岛素抵抗,这是糖尿病的第一步。
进一步地,已知香芹烯具有抗糖尿病和降低血脂功能,因此可以视为一种预防和治疗代谢紊乱的潜在介质。它的抗氧化、抗炎症和抗癌功能众所周知。经过一年的单独的重复的剂量实验已经证明了香芹烯对人体没有毒性。它可以溶解含胆石的胆固醇。它对于胃酸有中和作用,促进正常蠕动,因此可以减轻胃灼热以及胃食管返流疾病(GERD)。
2013年7月6日电子出版的欧洲药理学杂志EUR J PHARMACOL,2013年9月5日,715(1-3):46-55 DOI:10.1016/J. EJPHAR,JING L等人发表的文章证实了香芹烯对于高脂肪含量大鼠肥胖诱导的代谢紊乱方面的预防和治疗作用。在预处理中,香芹烯减少了白色和棕色脂肪组织的尺寸,降低了血清中的甘油三酯水平以及空腹血糖水平,阻止了用高脂肪食物喂养的C57BL/6小鼠的肝脂增加。在治疗中,香芹烯减少了肥胖的小鼠的血清中的甘油三酯、低密度脂蛋白胆固醇、空腹血糖水平、葡萄糖耐受度以及增加了高密度脂蛋白胆固醇。
进一步地,已知羽扇豆醇(也称为琼脂或羽扇醇)是具有抗炎功能的药理活性化合物。它的抗糖尿病和抗氧化特质也是已知的。它还可以对高固醇神经变性疾病早期表现出的异常提供良好的保护也是已知的。它的抗癌功效也是已知的。应该提到有效治疗剂量的羽扇豆醇不会对正常的细胞和组织产生毒性。
GUPTA R等人对羽扇豆醇的抗糖尿病和抗氧化能力进行了研究(2011年11月1日电子出版的NAT PROD RES期刊2012;26(12):1125-9.DOI:10.1080/14876419.2011.560845)。在他们的研究中,21天后糖尿病的恶化被羽扇豆醇抑制住了,导致糖化血红蛋白、血清葡萄糖以及一氧化氮水平的降低同时增加了血清中的胰岛素水平。此外,羽扇豆醇还增加了抗氧化物水平,降低了硫代巴比妥酸值(TBAR)含量。在KEISHI HATA等人(2008)年进行的研究中还证实了它的降胆固醇作用(Phytochemistry Letters I(4)中的文章:191-194,2008年12月,2008DOI:10.1016/j. phytol, 2008.09.007)。在这个研究中,羽扇豆醇强力阻止了小鼠胚胎成纤维细胞3T3-L1细胞中分化诱导剂刺激导致的甘油三酯的合成和脂类小滴的增加。还已知β-谷甾醇可以抑制肠道对胆固醇的吸收并减少血液中的胆固醇水平。β-谷甾醇还已知可以减少系统性炎症并增加免疫力。它的抗癌功效也是已知的。它的抗糖尿病以及抗氧化能力也是已知且具有参考资料的。IVORRA MD等人(PHARMAZIE 1990年4月;45(4):271-3)中表明,他们的研究证明β-谷甾醇-3-D-葡萄糖甙通过刺激胰岛素分泌保持胰脏的β细胞的完好。
此外,肉桂中的一种浓缩物MHCP已知是一种胰岛素类似物。它似乎可以和胰岛素协同作用。它还已知可以减少脂肪细胞对胰岛素的抵抗,从而改善葡萄糖代谢。
肉桂醛也具有已知的降血糖能力,这种能力可以抑制氧化应激。和表儿茶酸一样,肉桂醛也已知可以抑制tau蛋白和β淀粉样蛋白的聚合,这种聚合是阿兹海默病人大脑的特征。它还已知具有降低血脂和抗癌功效。
要解决的技术问题。
本发明的一个目标是提供一种新的药物成分,可以用作医药,尤其可以用于并发的或糖尿病血脂异常、神经变性疾病、癌症、细菌、病毒、真菌和寄生感染的治疗。
本发明的另外一个目标是提供一种新的药物成分,可以用作医药,尤其是可以用于治疗疾病,而且避免了上述的现有技术中的药物的全部或部分缺陷。本发明的另外一个目标是提供一种可以用作医药的药物成分,尤其是用于治疗糖尿病、血胆脂醇过多、高甘油三酯血症以及肥胖相关疾病。
本发明的另外一个目标是提供了一种药物成分,可以抑制糖尿病中循环单核细胞、巨噬细胞、白细胞、胰脏细胞的炎症表现。
本发明的另外一个目标是提供一种药物成分,可以保护分泌胰岛素的胰脏细胞免于细胞死和/或减少胰岛素抵抗和血胰岛素过多。
本发明的另外一个目标是提供一种药物成分,可以用作医药,治疗神经变性疾病,尤其是预防糖尿病和阿兹海默综合征病人常见的老年斑、氧化应激反应造成的组织损伤。
本发明的另外一个目标是提供一种药物成分,可以减少或甚至抑制病原体(病毒、细菌、寄生虫等)和它们的靶细胞之间的关联和聚合。
本发明的另外一个目标是提供一种药物成分,可以抑制细胞感染,尤其是HIV病毒和它的各种变体对于T细胞的感染,抑制病毒复制、免疫细胞衰老并激活相应的免疫反应。本发明的另外一个目标是提出一种药物成分,尤其是上述的那种,可以减少毒性,让病人可以吸收耐受。
发明简要说明。
为了解决上述的技术问题,本发明提供了一种药物成分,一般包括香芹烯、羽扇豆醇和药物媒介的混合物作为有效成分,药物媒介从下面选择:肉桂中的一种浓缩物MHCP、肉桂醛、β谷甾醇、姜黄色素、表儿茶酸及其混合物。
申请人实际发现这种药物成分证明对于病毒、细菌、真菌、寄生虫和癌症中的血脂异常、脂肪代谢障碍、代谢疾病、免疫疾病、神经变性疾病有效。
申请人还证实了所述成分的至少三个协同作用加强了本发明的药物成分对于现有技术部分提到的疾病的作用,这些疾病主要特征是增加了低密度脂蛋白胆固醇、甘油三酯,且减少了高密度脂蛋白胆固醇、高血糖、胰岛素抵抗、增加氧化应激反应、老年斑的形成/某些脂类和膜细胞(鞘糖脂以及趋化因子受体CXCR4蛋白质)的超表达、病原体对靶细胞的渗透、慢性炎症以及系统性免疫超活化。
申请人还发现根据本发明的药物成分对于调节过氧化物酶体增殖物活化受体PPAR、肝脏X受体以及视黄醇X受体有协同作用。
发明详细说明。
根据本发明的药物成分可以用作医药,尤其是用于预防和治疗糖尿病和病毒病原体相关的并发或连续的血脂异常、治疗癌症以及尤其是那些脂肪组织相关的疾病、治疗神经变性疾病、免疫疾病、感染疾病尤其是HIV感染。根据本发明的一个具体实施方式,本发明的药物成分进一步包括β-谷甾醇和肉桂中的一种浓缩物MHCP的混合或β-谷甾醇和肉桂醛的混合物或肉桂中的一种浓缩物MHCP和肉桂醛的混合物或β-谷甾醇、肉桂醛和/或表儿茶酸的混合物或肉桂醛和表儿茶酸的派生物的任何一种的混合物。
优选的,所述药物成分不包括肉桂中的一种浓缩物MHCP、肉桂醛和β-谷甾醇或表儿茶酸和其派生物的混合物。
作为例子,它包括,有效成分的总质量的质量占比为:香芹烯的质量占比大体等于或大于10%并且大体等于或小于55%,尤其是大体等于或大于20%,大体等于或小于40%,羽扇豆醇的百分比为大于等于15%大体小于等于55%,尤其是大于等于30%且小于等于40%,肉桂醛的百分比大体大于等于15%且小于等于45%,尤其是大于等于15%且小于等于40%,肉桂中的一种浓缩物MHCP的百分比大体大于等于25%且小于等于35%,如果所述药物成分含有β-谷甾醇的话,其百分比为大于等于10%小于等于45%,尤其是大体大于等于15%且小于等于30%。
当这种药物成分包括肉桂中的一种浓缩物MHCP或表儿茶酸和肉桂醛时,它们各自相对于有效成分的总质量的重量比例优选等于和大体等于15%。根据本发明的药物成分进一步包括至少一种合格的制药赋形剂。所述赋形剂可以是固体的也可以是液体的。可以从比如纯净水、乙醇、丙二醇、甘油、植物油、动物油、碳氢化合物、硅酮、糖比如葡萄糖、果糖、小麦淀粉、玉米淀粉、马铃薯淀粉、黄原胶、阿拉伯树胶、黄蓍胶、刺梧桐树胶、瓜尔豆胶、果胶、藻朊酸盐、角叉酸盐、琼脂、动物胶、纤维素及其派生物。
本发明的药物成分的用药方式可以是任何合适的方式,比如口服、直肠给药、外敷(比如局部外敷)、腹膜、全身性、静脉、肌肉、皮下或粘膜、尤其是舌下或膏药、或以胶囊的形式、固定在脂质体、微粒、微胶囊以及和纳米颗粒及类似的颗粒中。还应提到,作为适合口服的赋形剂的非限制性的例子,滑石粉、乳糖、淀粉及其派生物、纤维素及其派生物、聚乙二醇、丙烯酸合成体、凝胶、硬脂酸镁、动物、植物或合成脂肪、石蜡派生物、乙二醇、稳定剂、保存剂、抗氧化剂、增湿剂、防结块剂、分散剂、乳化剂、味觉改良剂、渗透剂、溶解剂等。本领域药物和药物成分的形成和给药方式是众所周知的,本领域技术人员尤其可以参照最新版的雷鸣登氏药学全书。
根据本发明,所述药物成分通过口服或静脉注射的方式给药效果更优。
进一步地,根据本发明所述的药物成分,可以以大于等于40mg/kg/24小时且小于等于200mg/kg/24小时根据需要此药物成分的哺乳动物的剂量进行一次或多次口服或静脉注射。
作为例子,本发明的药物成分可以用于预防或治疗尤其是感染了HIV病毒的病人接受抗逆转录病毒综合治疗之后的血脂异常、胰岛素抵抗、因治疗而引起的高脂血症,还可以预防或治疗动脉粥样硬化、心绞痛或心肌梗塞等心脏血管疾病、尤其是中风或大脑动脉瘤引起的颈动脉疾病、周边动脉疾病和肺栓塞等。更具优势的,本发明所述的药物成分可以用于慢性炎症病人和/或病原体和/或全身性免疫超活化和/或脂类不平衡和/或胆固醇细胞运送体失调等,尤其是糖尿病相关的组织、肥胖、艾滋、克罗恩病、肝细胞不足、肝性脂肪变性、胆囊炎、囊结石中至少一种引起的感染,包括1型糖尿病、自身免疫甲状腺炎、免疫、自身免疫葡萄膜炎和自身免疫网膜炎、舍格伦综合征、全身性红斑狼疮、各种硬化症、风湿性关节炎、硬皮病、多肌炎以及阿兹海默综合征、帕金森氏症、各种硬化症、肌萎缩性脊髓侧索硬化或沙尔科病、肾小球肾病中的痴呆血管、癌症尤其是和脂肪组织相关的疾病在内的自身免疫疾病的预防和治疗。
在治疗艾滋病的情况下,申请人已经证实本发明所述的药物成分至少体外治疗结果良好且对健康的肝脏细胞毒性很低。
本发明所述的药物成分的作用方式没有得到完全理解。很可能它同时作用于多个负责现有技术部分提到的疾病的机制。它通过协同调节作用作用于核受体,尤其是过氧化物酶体增殖物活化受体s(PPARs)和肝脏X受体以及视黄醇X受体,从而让细胞内的胆固醇可以流出,并抑制了促炎的细胞因子的产生、抑制了一些鞘脂类的产生和/或超表达和/或机能障碍,所述鞘脂类包括糖鞘脂类(比如酰基鞘鞍醇三己糖和单唾液酸神经节苷酯)、膜蛋白、包括低密度脂蛋白受体相关蛋白1(LRP1)、T细胞受体(TCR)以及趋化因子受体CXCR4蛋白质。它还可以抑制改编基质细胞衍生因子-1(SDF-1)、趋化因子受体CXCR4的同源配合基从而抑制改编基质细胞衍生因子-1(SDF-1)/趋化因子受体CXCR4轴系的形成,所述改编基质细胞衍生因子-1(SDF-1)/趋化因子受体CXCR4轴系在建立抑制免疫微环境、形成新的血液循环、肿瘤增长和转移方面起到重要的作用。
因此,根据本发明所述的药物成分可以解构并重新构建细胞的脂类构成,所述细胞尤其包括脂膜筏、细菌、寄生原生动物以及病毒的靶细胞,从而阻止这些微生物体区域的稳定,建立融合波群、训练突触和细胞内吞作用,以及最终将这些病原体渗透进细胞中。
此外,这些膜微型领地的脂类构成的变化,导致了形态的变化,其中的蛋白质的功能或功能障碍变化,尤其是G蛋白偶联受体的变化,最终改变了许多病理生理活动的细胞信号通路,所述病理生理活动包括病原体引起的感染、患免疫缺陷综合征、癌症、肥胖、代谢疾病、自身免疫疾病和神经变性疾病。
在感染介质的薄膜内也会发生脂类混乱,接着感染过程中涉及到的通信蛋白的形态会发生变化,它们和靶细胞连接在一起。这种机制适用于生物和生化性质和它们的靶细胞类似的病毒和细菌,尤其是在脂双层包膜内。
本发明所述的药物成分可以用于减少或抑制病原体、细胞的炎症表现、氧化应激、免疫细胞的衰老造成的轧染,增加天生具有适应性的免疫响应。因此,本发明所述的药物成分可以用于治疗病原体以及它们的各种变体,尤其是逆转录酶病毒(包括HIV-1和HIV-2以及肿瘤病毒和泡沫病毒在内的慢病毒载体)、麻疹病毒、流感病毒、天花病毒、黄热病病毒、西尼罗河病毒、水疱性口膜炎病毒(VSV)、乙肝病毒(HBV)、丙型肝炎病毒(HCV)、细胞巨化病毒(GVIV)、埃-巴二氏病毒(EBV)、人类疱疹病毒8型(HHV8)、埃博拉病毒、一些轮状病毒、一些无包被病毒引起的感染,用于细菌感染的治疗,包括埃希氏菌属大肠杆菌、结核分枝杆菌,用于恶性疟原虫感染的治疗,用于癌症的治疗。这些癌症包括艾滋病相关的癌症,包括卡波西肉瘤、伯基特淋巴瘤、免疫母细胞性淋巴结瘤、脑原发淋巴瘤、非霍奇金病(NHLH)、宫颈癌、未归类艾滋病癌症,包括口腔癌、胃癌、尤其是侵入性结肠或结肠直肠癌、直肠癌、肛门癌、肝癌、肝细胞性肝癌、胆囊癌、胰脏癌、肺癌,尤其是急性或慢性肺腺癌、白血病、各种骨髓瘤、霍奇金氏病、脑瘤以及其他神经系统局部疾病、膀胱癌、卵巢癌、子宫癌、睾丸癌、肾癌、前列腺癌和乳腺癌,尤其是和脂肪组织、骨瘤相关的疾病。
本发明还涉及包括根据本发明所述药物成分的药物的制备,以及用于治疗病原体、癌症尤其是和脂肪组织相关的癌症同时或时间上先后或间隔发作的糖尿病、血脂异常、肥胖、动脉粥样硬化、心脏血管疾病的抗糖尿病药物和/或降血脂药物和/或抗感染药物和/或抗癌药物,所述药物可以是混合也可以单独包装。
举例说明,所述抗糖尿病药物可以从双胍类药物、磺酰脲类药物和格列奈类药物、α-葡萄糖苷酶抑制剂、肠降血糖素包括胰高血糖素样肽-1(GLP-1)和胰岛素中选择。降低血脂的药物可以从抑制素、非诺贝特、依泽替米贝、尼克酸和消胆胺中选择。抗感染药物可以从抗逆转录病毒药物中选择,尤其是核苷或非核苷逆转录酶抑制剂、蛋白酶抑制剂、融合抑制剂、整合酶抑制剂、抗生素、抗寄生虫药、杀真菌药中选择。抗癌药可以从抗代谢药物(甲氨蝶呤、卡培他滨、五氟脲嘧啶)、烷化药物(顺氯氨铂、丝裂霉素C、白消安)和相关物(左旋溶肉瘤素、苯丁酸氮芥、环磷酰胺)、分子对有丝分裂纺锤体有作用的(长春碱、长春新碱、多西他赛)、1型酪氨酸激酶抑制剂(阿法替尼、厄洛替尼、舒尼替尼)、苏氨酸蛋白激酶抑制剂(维罗非尼、依维莫司、特姆莫司)、对拓扑异构酶有效的药物(道诺霉素、链霉素、表鬼臼毒素吡喃葡糖苷)、蛋白酶体抑制剂、DNA转甲基酶抑制剂、组蛋白脱乙酰基酶抑制剂、免疫调节剂(干扰素、贝伐单抗、利妥昔)、某些基因改变优先针对目标癌症细胞的病毒、谷胱甘肽、维他命C、叶醛酸钙以及它们的混合物,尤其是上述两种抗癌药物的混合剂,可以用于短距离放射治疗的放射药物和/或可注射或可吸收的有效代谢物。
本发明还涉及一种包括香芹烯、羽扇豆醇和/或β-谷甾醇、肉桂中的一种浓缩物MHCP和/或肉桂醛和可选择的姜黄色素和表儿茶酸的制备。
本发明还涉及一种饮食补充剂,其中包括香芹烯、羽扇豆醇、甲基羟基查耳酮聚合物(METHYLHYDRAOXYCHALCONE)和/或肉桂醛、β-谷甾醇以及它们的混合物和可选择的姜黄色素和表儿茶酸的结合。
定义。
术语“药物治疗”表示药物治疗和预防;在本发明的含义内,药物治疗通过施加药物、免疫系统或代谢作用至少部分恢复、至少部分修正或至少部分修复生理功能。
术语“病人”表示哺乳动物或人类。根据本发明的药物成分也可以用作医兽的医药。
术语“糖尿病人”表示1型糖尿病人、2型糖尿病人、妊娠期糖尿病人、尿崩症人以及肾性糖尿病人。
术语“血脂异常”表示根据有效标准确定的高血脂和血脂过少。
术语“动脉粥样硬化”表示由于脂肪(脂类,尤其是低密度脂蛋白胆固醇)堆积造成的硬化症引起的动脉弹性消失,即组成动脉壁(内膜),尤其是大型和中型动脉的的三个腔中的一个中的弹性消失。
术语“炎症”表示身体对抗入侵产生的一系列反应。可以是外源的比如伤口、感染、创伤或内源的为身体本身内部的自身免疫病原体。
术语“肝细胞不足”表示肝细胞功能变化引起的临床和生物表现,尤其是合成、净化和胆汁分泌功能方面的变化。
本发明中提到的“抗癌药物”是对癌细胞至少在体外具有作用的元素,不管其作用机制如何。本发明中提到的“作用”表示对癌细胞的摧毁或至少部分修复,可以限制癌细胞的扩散和/或它们的增殖。
术语“感染”表示细菌入侵生物体,更具体地说病原微生物比如细菌或病毒寻找寄主,通常是寻找一个细菌或病毒可以利用其构成物进行增殖的细胞。
本发明中提到的“食物补充剂”是用于补充正常饮食的食物,构成了营养成分或其它单独或结合起来具有营养或病理效果的物质的密集来源。
关于提到的抗糖尿病和/或降低血脂和/或抗癌药物,这里使用这些术语,除非另有规定,包括提到的化学成分的成分上的同分异构体、结构上的立体异构体、对映体以及非对映异构体。关于本发明所述的药物成分中的肉桂醛,除非另有规定,所述术语包括它的派生物,尤其是羟基肉桂醛(HCA)、2’-苯甲羧基肉桂醛(BCA)、形式二聚物,尤其是HCA-HCA、BCA-BCA和CA-CA。
本发明所述药物成分中的表儿茶酸,除非另有规定,所述术语包括它的派生物,尤其是儿茶酸、棓儿茶酸(GC)、表儿茶素没食子酸酯(ECG)、表没食子儿茶素(EGC)和表没食子儿茶酚没食子酸酯(EGCG)。
实施例。
下面的成分百分比是指相对于有效成分的总质量的重量百分比。
成分:香芹烯(40%)、羽扇豆醇(30%)和肉桂中的一种浓缩物MHCP(30%)。
成分1b:香芹烯(40%)、羽扇豆醇(30%)和肉桂醛(30%)。
成分2:香芹烯(40%)、羽扇豆醇(30%)、肉桂中的一种浓缩物MHCP(15%)以及肉桂醛(15%)。
成分3a:香芹烯(30%)、羽扇豆醇(30%)和肉桂中的一种浓缩物MHCP(40%)。
成分3b:香芹烯(30%)、羽扇豆醇(30%)和肉桂醛(40%)。
成分4a:香芹烯(15%)、羽扇豆醇(50%)、β-谷甾醇(10%)以及肉桂中的一种浓缩物(40%)。
成分5a:香芹烯(20%)、羽扇豆醇(20%)、β-谷甾醇(40%)和肉桂中的一种浓缩物MHCP(20%)。
成分5b:香芹烯(20%)、羽扇豆醇(20%)、β-谷甾醇(40%)以及肉桂醛(20%)。
成分6a:香芹烯(25%)、羽扇豆醇(30%)、β-谷甾醇(15%)和肉桂中的一种浓缩物MHCP(25%)。
成分6b:香芹烯(25%)、羽扇豆醇(35%)、β-谷甾醇(15%)和肉桂醛(25%)。
成分7a:香芹烯(50%)、羽扇豆醇(15%)、β-谷甾醇(10%)和肉桂中的一种浓缩物MHCP(25%)。
成分7b:香芹烯(50%)、羽扇豆醇(15%)、β-谷甾醇(10%)和肉桂醛(25%)。
实验结果。
研究了不同的细胞:小鼠胚胎成纤维细胞3T3-L1细胞、单核细胞、巨噬细胞、白细胞、肝细胞和脂肪细胞。选择它们是基于它们增加脂类小滴的能力。这些细胞,尤其是白细胞在糖尿病中有炎症表现。
这些细胞保存在达尔伯克(氏)改良伊格尔(氏)培养基中,补充以10%的胎牛血清(FBS)和1%的杀真菌抗生素溶剂(MPS)中,其中包括标准生长条件的青霉素、链霉素、两性霉素B(5%的二氧化碳、37摄氏度、潮湿环境)。上述成分在二甲基亚砜DMSO中溶解并稀释。上述细胞在完全细胞培养基中用溶液(10-80μM)处理48小时。所有处理和控制记录根据上述条件准备。上述溶液尽管在有类似罗西格列酮这样的促进分化的介质的存在的情况下选择性抑制了小鼠胚胎成纤维细胞3T3-L1细胞分化成脂肪细胞。这种分化的影响由油红O染色量化:观察到了分化和脂肪形成相关的基因和蛋白质表达的变化。上述溶液还显著抑制了单核细胞、巨噬细胞、白细胞、肝细胞中的脂类小滴的增加,调节了过氧化物酶体增殖物活化受体y(PPARy)的表达,导致了促炎细胞因子的减少,抑制了一些膜脂质(鞘脂类、尤其是鞘糖脂)和一些膜蛋白的形成、超表达和/或功能障碍。它们还减少了它们的靶细胞的病原体的密切关系。
这些结果整体表明这些药物成分抑制了脂肪组织的产生从而减少了胰岛素抑制。还可以外推到在代谢综合征的病理生理中起了重要作用的内脏脂肪组织(TAV)和皮下脂肪组织(TA se)。此外,这种药物成分可以抑制肿瘤发展并通过抑制分泌癌症相关的脂肪细胞(CAA),尤其是促炎性细胞因子(肿瘤坏死细胞TNFα和1Lip、白介素6和白介素8)、促进血管生成分子(比如血管内皮生长因子VEGF)、趋化因子(单核细胞趋化蛋白-1 MCP-1以及1-磷酸-鞘氨醇S1P)、生长因子(比如肝细胞生长因子HGF)、细胞外基质和自由脂肪酸的重构和释放来抑制对于抗癌治疗的抵抗。它减少了甚至抑制了病原体和它们的各种变体的感染。因此,这种药物成分可以正确用于肥胖、糖尿病、血脂异常以及它们引起的神经变性疾病、病原体、癌症尤其是和脂肪组织相关的癌症比如乳腺癌和前列腺癌引起的感染。
权利要求书(按照条约第19条的修改)
1.一种药物成分,其特征在于它包括香芹烯、羽扇豆醇和/或β-谷甾醇、肉桂醛和/或肉桂中的一种浓缩物MHCP以及可选的姜黄色素和表儿茶酸。
2.根据权利要求1所述的药物成分,其特征在于,所述药物成分进一步包括β-谷甾醇和肉桂醛的混合物或β-谷甾醇和肉桂中的一种浓缩物MHCP的混合物或肉桂中的一种浓缩物MHCP和肉桂醛的混合物或肉桂醛和/或表儿茶酸和/或姜黄色素的混合物。
3.根据上述任一权利要求所述的药物成分,其特征在于所述药物成分包括质量占有效物成分总质量的百分比为香芹烯的质量百分比大于等于10%且小于等于55%,尤其是大体大于等于20%且大体小于等于40%;羽扇豆醇百分比大体大于等于15%且小于等于55%,尤其是大体大于等于30%且大体小于等于40%;肉桂醛的百分比大于等于15%且小于等于45%,尤其是大于等于20%且大体小于等于40%;肉桂中的一种浓缩物MHCP大体大于等于15%且大体小于等于40%,尤其大体大于等于25%;如果含有β-谷甾醇这种成分的话,所述β-谷甾醇的百分比如果不大于35%的话,大体大于等于10%且大体小于等于45%,尤其是大于等于15%并且小于等于30%。
4.根据上述任一权利要求所述的药物成分在制备治疗尤其是感染了HIV病毒的病人接受抗逆转录病毒综合治疗由于治疗而引起的血脂异常、胰岛素抵抗、医源性血脂异常的预防和治疗中,用于预防和治疗动脉粥样硬化、冠状动脉或静脉心脏疾病包括心绞痛或心肌梗死、颈动脉疾病尤其是中风和动脉瘤脑性麻痹、周围动脉疾病和肺栓塞等疾病药物中的应用。
5.根据上述任一权利要求所述的药物成分在制备治疗慢性炎症疾病和/或病原体和/或全身性免疫超活化和/或脂类不平衡和/或细胞胆固醇转运体功能障碍,尤其是糖尿病、肥胖、艾滋病、克罗恩病、肝细胞不足、肝性脂肪变性、胆囊炎、囊结石等组织慢性炎症疾病,包括1型糖尿病、自身免疫疾病、自身免疫甲状腺炎、自身免疫肝脏疾病、自身免疫葡萄膜炎和自身免疫视网膜炎、干燥综合征、全身性红斑狼疮、各种硬化症、风湿性关节炎、硬皮病、多肌炎、混合型结缔组织疾病等全身性免疫疾病,包括阿兹海默综合征、帕金森综合征、各种硬化症、肌萎缩性脊髓侧索硬化和夏科氏三联症、血管性痴呆在内的神经变性疾病,以及癌症尤其是脂肪组织相关的癌症中的肾小球肾病等疾病药物中的应用。
6.根据权利要求1-3中任一所述的药物成分,其特征在于所述药物成分解构并重新构造细胞和感染成分内的脂类成分,尤其是细胞膜,修复其中的蛋白质的形态,从而改变并阻止这些微型领地膜的稳定、阻止病原体渗透进入细胞中以及许多病理生理进程尤其是感染、获得性免疫缺陷综合征、癌症、肥胖、代谢疾病、自身免疫疾病和神经变性疾病中中的细胞信号通路。
7.根据权利要求6所述的药物成分在制备治疗病原体和它们的各种变体尤其是逆转录酶病毒(包括HIV-1和HIV-2以及肿瘤病毒和泡沫病毒在内的慢病毒载体)、麻疹病毒、流感病毒、天花病毒、黄热病病毒、西尼罗河病毒、水疱性口膜炎病毒(VSV)、乙肝病毒(HBV)、丙型肝炎病毒(HCV)、细胞巨化病毒(GVIV)、埃-巴二氏病毒(EBV)、人类疱疹病毒8型(HHV8)、埃博拉病毒、一些轮状病毒引起的感染的治疗;用于细菌感染的治疗,包括埃希氏菌属大肠杆菌、结核分枝杆菌;用于恶性疟原虫感染的治疗;用于癌症的治疗,所述癌症包括艾滋病相关的癌症,包括卡波西肉瘤、伯基特淋巴瘤、免疫母细胞性淋巴结瘤、脑原发淋巴瘤、非霍奇金病(NHLH)、宫颈癌、未归类艾滋病癌症,包括口腔癌、胃癌、尤其是侵入性结肠或结肠直肠癌、直肠癌、肛门癌、肝癌、肝细胞性肝癌、胆囊癌、胰脏癌、肺癌,尤其是急性或慢性肺腺癌、白血病、各种骨髓瘤、霍奇金氏病、脑瘤以及其他神经系统局部疾病、膀胱癌、卵巢癌、子宫癌、睾丸癌、肾癌、前列腺癌和乳腺癌,尤其是和脂肪组织、骨瘤相关的疾病药物中的应用。
8.根据上述任一权利要求所述的药物成分的制备方法,其特征在于,所述药物成分单独混合或调配的用于治疗病原体感染、癌症尤其是和脂肪组织相关的癌症引起的同时或时间上先后或间隔发作的糖尿病、血脂异常、肥胖、动脉粥样硬化、心脏血管疾病的抗糖尿病药物和/或降血脂药物和/或抗感染药物和/或抗癌药物。
9.根据权利要求8所述的药物成分制备方法,其特征在于所述抗糖尿病药物可以从双胍类药物、磺酰脲类药物和格列奈类药物、α-葡萄糖苷酶抑制剂、肠降血糖素包括胰高血糖素样肽-1(GLP-1)和胰岛素中选择;降低血脂的药物可以从抑制素、非诺贝特、依泽替米贝、尼克酸和消胆胺中选择;抗感染药物可以从抗逆转录病毒药物中选择,尤其是核苷或非核苷逆转录酶抑制剂、蛋白酶抑制剂、融合抑制剂、整合酶抑制剂、抗生素、抗寄生虫药、杀真菌药中选择;抗癌药可以从抗代谢药物(甲氨蝶呤、卡培他滨、五氟脲嘧啶)、烷化药物(顺氯氨铂、丝裂霉素C、白消安)和相关物(左旋溶肉瘤素、苯丁酸氮芥、环磷酰胺)、分子对有丝分裂纺锤体有作用的(长春碱、长春新碱、多西他赛)、1型酪氨酸激酶抑制剂(阿法替尼、厄洛替尼、舒尼替尼)、苏氨酸蛋白激酶抑制剂(维罗非尼、依维莫司、特姆莫司)、对拓扑异构酶有效的药物(道诺霉素、链霉素、表鬼臼毒素吡喃葡糖苷)、蛋白酶体抑制剂、DNA转甲基酶抑制剂、组蛋白脱乙酰基酶抑制剂、免疫调节剂(干扰素、贝伐单抗、利妥昔)、某些基因改变优先针对目标癌症细胞的病毒、谷胱甘肽、维他命C、叶醛酸钙以及它们的混合物,尤其是上述两种抗癌药物的混合剂,可以用于镭疗法的放射药物和/或可注射或可吸收的有效代谢物。
Claims (12)
1.一种药物成分,其特征在于包括香芹烯,羽扇豆醇,以及肉桂中的一种浓缩物MHCP、肉桂醛、β-谷甾醇、姜黄色素和表儿茶酸中的一种或多种的组合选择的药理有效成分以及它们的各种组合。
2.根据权利要求1所述的一种药物成分,其特征在于,所述药物成分还包括β-谷甾醇、肉桂中的一种浓缩物MHP的组合或β-谷甾醇和肉桂醛的组合或肉桂中的一种浓缩物MHCP和肉桂醛的组合或β-谷甾醇和肉桂醛和/或表儿茶酸的组合或肉桂醛和任何一种表儿茶酸派生物的组合。
3.根据上述任一权利要求所述的药物成分,其特征在于所述药物成分包括质量占有效物成分总质量的百分比为:香芹烯的质量百分比大于等于10%且小于等于55%,尤其是大体大于等于20%且大体小于等于40%;羽扇豆醇百分比大体大于等于15%且小于等于55%,尤其是大体大于等于30%且大体小于等于40%;肉桂醛的百分比大于等于15%且小于等于45%,尤其是大于等于20%且大体小于等于40%;肉桂中的一种浓缩物MHCP大体大于等于15%且大体小于等于40%,尤其大体大于等于25%;如果含有β-谷甾醇这种成分的话,所述β-谷甾醇的百分比如果不大于35%的话,大体大于等于10%且大体小于等于45%,尤其是大于等于15%并且小于等于30%。
4.根据上述任何一项权利要求所述的药物成分在制备治疗尤其是感染了HIV病毒的病人接受抗逆转录病毒综合治疗由于治疗而引起的血脂异常、胰岛素抵抗、医源性血脂异常的预防和治疗中,用于预防和治疗动脉粥样硬化、冠状动脉或静脉心脏疾病包括心绞痛或心肌梗死、颈动脉疾病尤其是中风和动脉瘤脑性麻痹、周围动脉疾病和肺栓塞等疾病药物中的应用。
5.根据上述任一权利要求所述的药物成分在制备治疗慢性炎症疾病和/或病原体和/或全身性免疫超活化和/或脂类不平衡和/或细胞胆固醇转运体功能障碍,尤其是糖尿病、肥胖、艾滋病、克罗恩病、肝细胞不足、肝性脂肪变性、胆囊炎、囊结石等组织慢性炎症疾病,包括1型糖尿病、自身免疫疾病、自身免疫甲状腺炎、自身免疫肝脏疾病、自身免疫葡萄膜炎和自身免疫视网膜炎、干燥综合征、全身性红斑狼疮、各种硬化症、风湿性关节炎、硬皮病、多肌炎、混合型结缔组织疾病等全身性免疫疾病,包括阿兹海默综合征、帕金森综合征、各种硬化症、肌萎缩性脊髓侧索硬化和夏科氏三联症、血管性痴呆在内的神经变性疾病,以及癌症尤其是脂肪组织相关的癌症中的肾小球肾病等疾病药物中的应用。
6.根据上述任一权利要求所述的药物成分,所述药物成分解构并重新构造细胞内的脂类成分,尤其是脂膜筏、目标细菌、寄生原生动物和病毒,从而阻止这些微生物、微型领地的稳定、建立融合体、形成突触和细胞内吞作用从而最终将这些病原体渗透进入细胞中。
7.根据上述任一权利要求所述的药物成分,其特征在于根据权利要求6所述的脂膜成分的变化改变了其中的蛋白质尤其是G蛋白偶联受体的功能活动和功能障碍活动,限制许多病理生理进程尤其病原体感染、获得性免疫缺陷综合征、癌症、肥胖、代谢疾病、自身免疫疾病和神经变性疾病中的细胞信号通路。
8.根据上述任一权利要求所述的药物成分,所述药物成分减少或抑制了病原体感染、细胞的炎症表现、氧化应激、免疫细胞的衰老并增加固有的适应性的免疫抵抗反应。
9.根据上述任一权利要求所述的药物成分,用于病原体以及它们的各种变体包括逆转录酶病毒(包括HIV-1和HIV-2在内的慢病毒载体、肿瘤病毒和泡沫病毒)、麻疹病毒、流感病毒、天花病毒、黄热病病毒、西尼罗河病毒、水疱性口膜炎病毒(VSV)、乙肝病毒(HBV)、丙型肝炎病毒(HCV)、细胞巨化病毒(GVIV)、埃-巴二氏病毒(EBV)、人类疱疹病毒8型(HHV8)、埃博拉病毒、一些轮状病毒、一些无包被病毒引起的感染的治疗;用于细菌感染的治疗,包括埃希氏菌属大肠杆菌、结核分枝杆菌;用于恶性疟原虫感染的治疗;用于癌症的治疗。
10.根据上述任一权利要求所述的药物成分,用于治疗癌症,包括艾滋病相关的癌症,包括卡波西肉瘤、伯基特淋巴瘤、免疫母细胞性淋巴结瘤、脑原发淋巴瘤、非霍奇金病(NHLH)、宫颈癌、未归类艾滋病癌症,包括口腔癌、胃癌、尤其是侵入性结肠或结肠直肠癌、直肠癌、肛门癌、肝癌、肝细胞性肝癌、胆囊癌、胰脏癌、肺癌,尤其是急性或慢性肺腺癌、白血病、各种骨髓瘤、霍奇金氏病、脑瘤以及其他神经系统局部疾病、膀胱癌、卵巢癌、子宫癌、睾丸癌、肾癌、前列腺癌和乳腺癌,尤其是和脂肪组织、骨瘤相关的疾病。
11.一种药物成分制备方法,其特征在于所述药物成分包括根据上述任一权利要求所述的药物成分,以及单独混合或调制的用于治疗同时或时间上先后或间隔发作的病原体感染、癌症尤其是和脂肪组织相关的癌症引起的糖尿病、血脂异常、肥胖、动脉粥样硬化、心脏血管疾病和的抗糖尿病药物和/或降血脂药物和/或抗感染药物和/或抗癌药物中至少一个。
12.根据权利要求11所述的药物制备方法,其特征在于所述抗糖尿病药物可以从双胍类药物、磺酰脲类药物和格列奈类药物、α-葡萄糖苷酶抑制剂、肠降血糖素包括胰高血糖素样肽-1(GLP-1)和胰岛素中选择;降低血脂的药物可以从抑制素、非诺贝特、依泽替米贝、尼克酸和消胆胺中选择;抗感染药物可以从抗逆转录病毒药物中选择,尤其是核苷或非核苷逆转录酶抑制剂、蛋白酶抑制剂、融合抑制剂、整合酶抑制剂、抗生素、抗寄生虫药、杀真菌药中选择;抗癌药可以从抗代谢药物(甲氨蝶呤、卡培他滨、五氟脲嘧啶)、烷化药物(顺氯氨铂、丝裂霉素C、白消安)和相关物(左旋溶肉瘤素、苯丁酸氮芥、环磷酰胺)、分子对有丝分裂纺锤体有作用的(长春碱、长春新碱、多西他赛)、1型酪氨酸激酶抑制剂(阿法替尼、厄洛替尼、舒尼替尼)、苏氨酸蛋白激酶抑制剂(维罗非尼、依维莫司、特姆莫司)、对拓扑异构酶有效的药物(道诺霉素、链霉素、表鬼臼毒素吡喃葡糖苷)、蛋白酶体抑制剂、DNA转甲基酶抑制剂、组蛋白脱乙酰基酶抑制剂、免疫调节剂(干扰素、贝伐单抗、利妥昔)、某些基因改变优先针对目标癌症细胞的病毒、谷胱甘肽、维他命C、叶醛酸钙以及它们的混合物,尤其是上述两种抗癌药物的混合剂,可以用于短距离放射治疗的放射药物和/或可注射或可吸收的有效代谢物。
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FR1770014A FR3061658A1 (fr) | 2017-01-07 | 2017-01-07 | Composition pharmaceutique comprenant en tant que principe actif une combinaison de d-limoneme, de lupeol et du cinnamaldehyde et/ou du methylhydroxychalcone polymere et/ou du beta-sitosterol et/ou de |
FR17/70014 | 2017-01-07 | ||
FR1771175A FR3061659B1 (fr) | 2017-01-07 | 2017-11-07 | Composition pharmaceutique comprenant en tant que principe actif une combinaison de d-limoneme, de lupeol et du cinnamaldehyde et/ou de l'epicatechine et/ou du methylhydroxychalcone polymere et/ou d |
FR17/71175 | 2017-11-07 | ||
PCT/IB2017/057731 WO2018127748A1 (fr) | 2017-01-07 | 2017-12-07 | Composition pharmaceutique utilisée pour traiter les troubles du syndrome métabolique, les maladies infectieuses, et leurs complications. |
Publications (1)
Publication Number | Publication Date |
---|---|
CN110139643A true CN110139643A (zh) | 2019-08-16 |
Family
ID=58632521
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201780082728.5A Pending CN110139643A (zh) | 2017-01-07 | 2017-12-07 | 一种用于治疗代谢紊乱综合征、炎症及其并发症的药物成分 |
Country Status (5)
Country | Link |
---|---|
US (1) | US20200268770A1 (zh) |
EP (1) | EP3565536A1 (zh) |
CN (1) | CN110139643A (zh) |
FR (2) | FR3061658A1 (zh) |
WO (1) | WO2018127748A1 (zh) |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN111000849A (zh) * | 2019-12-19 | 2020-04-14 | 淮阴师范学院 | 羽扇豆醇dyc-6的应用和产品 |
CN111840262A (zh) * | 2020-07-15 | 2020-10-30 | 广东工业大学 | 肉桂醛衍生物在制备预防和/或治疗新型冠状病毒感染药物中的应用 |
CN113648421A (zh) * | 2021-08-19 | 2021-11-16 | 中山大学中山眼科中心 | 磺酰脲类药物在制备治疗葡萄膜炎的药物中的应用 |
CN115120599A (zh) * | 2021-03-27 | 2022-09-30 | 盖伊·福斯汀·蒙卡姆·尼切 | 一种用于抑制磷脂双分子层病毒传染性、治疗相关疾病及其并发症的药物组合物 |
Families Citing this family (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR3061658A1 (fr) * | 2017-01-07 | 2018-07-13 | Guy Faustin Monkam Nitcheu | Composition pharmaceutique comprenant en tant que principe actif une combinaison de d-limoneme, de lupeol et du cinnamaldehyde et/ou du methylhydroxychalcone polymere et/ou du beta-sitosterol et/ou de |
US11040027B2 (en) | 2017-01-17 | 2021-06-22 | Heparegenix Gmbh | Protein kinase inhibitors for promoting liver regeneration or reducing or preventing hepatocyte death |
FR3100128B1 (fr) * | 2019-08-30 | 2022-02-18 | Nitcheu Guy Faustin Monkam | Composition pharmaceutique destinée à inhiber l’infectiosité du VIH, à traiter le syndrome d’immunodéficience acquise (SIDA) et ses complications |
GB202113028D0 (en) * | 2021-09-13 | 2021-10-27 | Ucl Business Ltd | Sterol therapy |
Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20040137090A1 (en) * | 2003-01-14 | 2004-07-15 | Wright Jonathan V. | Formulation for insulin and glucose control |
US20050267221A1 (en) * | 2004-05-14 | 2005-12-01 | Research Development Foundation | Use of curcumin and analogues thereof as inhibitors of ACC2 |
US20060286182A1 (en) * | 2005-06-21 | 2006-12-21 | Abeille Pharmaceuticals, Inc. | Synergistic cinnamon combinations and methods for enhancing insulin activity |
US20070196520A1 (en) * | 2004-03-01 | 2007-08-23 | Fhg Corporation D/B/A Nutraceuticals | Methods and materials for reducing or eliminating risk factors associated with syndrome x |
WO2007098680A1 (fr) * | 2006-02-28 | 2007-09-07 | Gang Shu | Utilisations de d-limonène, de la plante ou de son huile volatile contenant du d-limonène pour la préparation de médicaments destinés à la prévention et au traitement du diabète |
WO2009015459A1 (en) * | 2007-07-27 | 2009-02-05 | Innovative Life Sciences Corporation | Herbal product comprising cinnamon and chocolate for treating diabetes and reducing the risk of cardiovascular disease |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR3061658A1 (fr) * | 2017-01-07 | 2018-07-13 | Guy Faustin Monkam Nitcheu | Composition pharmaceutique comprenant en tant que principe actif une combinaison de d-limoneme, de lupeol et du cinnamaldehyde et/ou du methylhydroxychalcone polymere et/ou du beta-sitosterol et/ou de |
-
2017
- 2017-01-07 FR FR1770014A patent/FR3061658A1/fr not_active Withdrawn
- 2017-11-07 FR FR1771175A patent/FR3061659B1/fr active Active
- 2017-12-07 WO PCT/IB2017/057731 patent/WO2018127748A1/fr unknown
- 2017-12-07 US US16/481,853 patent/US20200268770A1/en not_active Abandoned
- 2017-12-07 CN CN201780082728.5A patent/CN110139643A/zh active Pending
- 2017-12-07 EP EP17825613.7A patent/EP3565536A1/fr active Pending
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20040137090A1 (en) * | 2003-01-14 | 2004-07-15 | Wright Jonathan V. | Formulation for insulin and glucose control |
US20070196520A1 (en) * | 2004-03-01 | 2007-08-23 | Fhg Corporation D/B/A Nutraceuticals | Methods and materials for reducing or eliminating risk factors associated with syndrome x |
US20050267221A1 (en) * | 2004-05-14 | 2005-12-01 | Research Development Foundation | Use of curcumin and analogues thereof as inhibitors of ACC2 |
US20060286182A1 (en) * | 2005-06-21 | 2006-12-21 | Abeille Pharmaceuticals, Inc. | Synergistic cinnamon combinations and methods for enhancing insulin activity |
WO2007098680A1 (fr) * | 2006-02-28 | 2007-09-07 | Gang Shu | Utilisations de d-limonène, de la plante ou de son huile volatile contenant du d-limonène pour la préparation de médicaments destinés à la prévention et au traitement du diabète |
WO2009015459A1 (en) * | 2007-07-27 | 2009-02-05 | Innovative Life Sciences Corporation | Herbal product comprising cinnamon and chocolate for treating diabetes and reducing the risk of cardiovascular disease |
Non-Patent Citations (3)
Title |
---|
LI JING等: "Preventive and ameliorating effects of citrus D-limonene on dyslipidemia and hyperglycemia in mice with high-fat diet-induced obesity", 《EUROPEAN JOURNAL OF PHARMACOLOGY》 * |
MANJESHWAR SHRINATH BALIGA等: "Aegle marmelos (L.) Correa (Bael) and Its Phytochemicals in the Treatment and Prevention of Cancer", 《INTEGRATIVE CANCER THERAPIES》 * |
季宇彬等: "《中药抗肿瘤有效成分药理与应用》", 31 May 1998, 哈尔滨:黑龙江科学技术出版社 * |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN111000849A (zh) * | 2019-12-19 | 2020-04-14 | 淮阴师范学院 | 羽扇豆醇dyc-6的应用和产品 |
CN111840262A (zh) * | 2020-07-15 | 2020-10-30 | 广东工业大学 | 肉桂醛衍生物在制备预防和/或治疗新型冠状病毒感染药物中的应用 |
CN115120599A (zh) * | 2021-03-27 | 2022-09-30 | 盖伊·福斯汀·蒙卡姆·尼切 | 一种用于抑制磷脂双分子层病毒传染性、治疗相关疾病及其并发症的药物组合物 |
CN113648421A (zh) * | 2021-08-19 | 2021-11-16 | 中山大学中山眼科中心 | 磺酰脲类药物在制备治疗葡萄膜炎的药物中的应用 |
Also Published As
Publication number | Publication date |
---|---|
US20200268770A1 (en) | 2020-08-27 |
FR3061659A1 (fr) | 2018-07-13 |
WO2018127748A1 (fr) | 2018-07-12 |
FR3061658A1 (fr) | 2018-07-13 |
EP3565536A1 (fr) | 2019-11-13 |
FR3061659B1 (fr) | 2020-02-21 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN110139643A (zh) | 一种用于治疗代谢紊乱综合征、炎症及其并发症的药物成分 | |
JP7174102B2 (ja) | ミトコンドリア機能向上と、神経変性疾患および認知障害治療とのための組成物および方法 | |
Liao et al. | Myricetin alleviates pathological cardiac hypertrophy via TRAF6/TAK1/MAPK and Nrf2 signaling pathway | |
CA2946825C (en) | Muscle atrophy inhibitor containing quercetin glycoside | |
CN103945848B (zh) | 被取代的喹唑啉酮的口服即释制剂 | |
Tanabe et al. | Epicatechin limits renal injury by mitochondrial protection in cisplatin nephropathy | |
AU2018200791A1 (en) | Enhancing autophagy or increasing longevity by administration of urolithins or precursors thereof | |
JP6201054B2 (ja) | モノアセチルジアシルグリセロール化合物を有効成分として含有する血液癌または癌転移抑制用組成物 | |
KR20160101786A (ko) | Fam19a5 단백질을 포함하는 비만 예방 또는 치료용 조성물 및 이를 이용한 비만 치료제의 스크리닝 방법 | |
AU2018203677A1 (en) | Modified polyphenol compositions | |
JP2019511514A (ja) | ブドウ抽出物およびそれに関する方法 | |
KR20120003693A (ko) | 적포도 추출물, 녹차 추출물, 대두 추출물 및 l-카르니틴을 유효성분으로 함유하는 항비만 조성물 | |
CN110507647B (zh) | 亚硫酸氢钠穿心莲内酯在制备用于治疗高血脂病症的药物中的应用 | |
KR20130050967A (ko) | axial―equatorial aryl배향의 furofuran형 리그난을 함유하는 골 형성 촉진용 약학적 조성물 및 이의 조성물을 포함하는 약학적 제제, 기능성 식품 및 건강 식품 | |
CN111067900B (zh) | 治疗或预防肥胖或其相关疾病的化合物及其应用 | |
CN101057674A (zh) | 一种用于防治糖尿病的组合物 | |
CN101461819A (zh) | 芒果苷钙盐作为过氧化物酶增殖物激活受体激动剂的用途 | |
KR20150051387A (ko) | 큰열매모자반 추출물을 함유하는 염증성 질환의 예방 및 치료용 조성물 | |
CN111686239B (zh) | 抗真菌化合物的应用 | |
KR20170141914A (ko) | 베르바민을 유효성분으로 포함하는 면역질환의 예방 또는 치료용 조성물 | |
JP2008231080A (ja) | 脂肪細胞からのレプチン分泌促進剤 | |
WO2013058627A2 (ko) | 레바미피드를 유효성분으로 포함하는 비만의 예방 또는 치료용 조성물 | |
TWI439273B (zh) | 以靈芝酸保護心臟免於壞死或損傷之方法與組成物 | |
KR101613252B1 (ko) | 아르기나아제 억제제를 함유하는 비만 및 지방간 예방 또는 치료용 조성물 | |
KR101968398B1 (ko) | 면역계 부작용이 억제된 암치료용 약학 조성물 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
RJ01 | Rejection of invention patent application after publication | ||
RJ01 | Rejection of invention patent application after publication |
Application publication date: 20190816 |