CN115120599A - 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 - Google Patents
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 Download PDFInfo
- Publication number
- CN115120599A CN115120599A CN202210292412.1A CN202210292412A CN115120599A CN 115120599 A CN115120599 A CN 115120599A CN 202210292412 A CN202210292412 A CN 202210292412A CN 115120599 A CN115120599 A CN 115120599A
- Authority
- CN
- China
- Prior art keywords
- substantially equal
- pharmaceutical composition
- proportion
- sitosterol
- lupeol
- 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
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 47
- 241000700605 Viruses Species 0.000 title description 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title description 10
- 230000002401 inhibitory effect Effects 0.000 title description 10
- 201000010099 disease Diseases 0.000 title description 8
- 150000003904 phospholipids Chemical class 0.000 title description 5
- 244000052769 pathogen Species 0.000 claims abstract description 23
- 239000004599 antimicrobial Substances 0.000 claims abstract description 5
- 229960005475 antiinfective agent Drugs 0.000 claims abstract description 4
- XMGQYMWWDOXHJM-JTQLQIEISA-N (+)-α-limonene Chemical compound CC(=C)[C@@H]1CCC(C)=CC1 XMGQYMWWDOXHJM-JTQLQIEISA-N 0.000 claims description 48
- 239000000203 mixture Substances 0.000 claims description 36
- 210000004027 cell Anatomy 0.000 claims description 28
- VFLDPWHFBUODDF-FCXRPNKRSA-N curcumin Chemical compound C1=C(O)C(OC)=CC(\C=C\C(=O)CC(=O)\C=C\C=2C=C(OC)C(O)=CC=2)=C1 VFLDPWHFBUODDF-FCXRPNKRSA-N 0.000 claims description 26
- KJPRLNWUNMBNBZ-QPJJXVBHSA-N (E)-cinnamaldehyde Chemical compound O=C\C=C\C1=CC=CC=C1 KJPRLNWUNMBNBZ-QPJJXVBHSA-N 0.000 claims description 25
- 229940117916 cinnamic aldehyde Drugs 0.000 claims description 25
- KJPRLNWUNMBNBZ-UHFFFAOYSA-N cinnamic aldehyde Natural products O=CC=CC1=CC=CC=C1 KJPRLNWUNMBNBZ-UHFFFAOYSA-N 0.000 claims description 25
- 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 description 25
- 229940076810 beta sitosterol Drugs 0.000 claims description 24
- LGJMUZUPVCAVPU-UHFFFAOYSA-N beta-Sitostanol Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(C)CCC(CC)C(C)C)C1(C)CC2 LGJMUZUPVCAVPU-UHFFFAOYSA-N 0.000 claims description 24
- NJKOMDUNNDKEAI-UHFFFAOYSA-N beta-sitosterol Natural products CCC(CCC(C)C1CCC2(C)C3CC=C4CC(O)CCC4C3CCC12C)C(C)C NJKOMDUNNDKEAI-UHFFFAOYSA-N 0.000 claims description 24
- 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 description 24
- 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 description 24
- 229950005143 sitosterol Drugs 0.000 claims description 24
- WMBWREPUVVBILR-WIYYLYMNSA-N (-)-Epigallocatechin-3-o-gallate Chemical compound O([C@@H]1CC2=C(O)C=C(C=C2O[C@@H]1C=1C=C(O)C(O)=C(O)C=1)O)C(=O)C1=CC(O)=C(O)C(O)=C1 WMBWREPUVVBILR-WIYYLYMNSA-N 0.000 claims description 22
- WMBWREPUVVBILR-UHFFFAOYSA-N GCG Natural products C=1C(O)=C(O)C(O)=CC=1C1OC2=CC(O)=CC(O)=C2CC1OC(=O)C1=CC(O)=C(O)C(O)=C1 WMBWREPUVVBILR-UHFFFAOYSA-N 0.000 claims description 22
- 229940030275 epigallocatechin gallate Drugs 0.000 claims description 22
- 208000015181 infectious disease Diseases 0.000 claims description 21
- 238000011282 treatment Methods 0.000 claims description 16
- 229940109262 curcumin Drugs 0.000 claims description 13
- 235000012754 curcumin Nutrition 0.000 claims description 13
- 239000004148 curcumin Substances 0.000 claims description 13
- VFLDPWHFBUODDF-UHFFFAOYSA-N diferuloylmethane Natural products C1=C(O)C(OC)=CC(C=CC(=O)CC(=O)C=CC=2C=C(OC)C(O)=CC=2)=C1 VFLDPWHFBUODDF-UHFFFAOYSA-N 0.000 claims description 13
- 241001678559 COVID-19 virus Species 0.000 claims description 12
- 150000002632 lipids Chemical class 0.000 claims description 10
- 206010028980 Neoplasm Diseases 0.000 claims description 9
- 201000011510 cancer Diseases 0.000 claims description 8
- 239000002246 antineoplastic agent Substances 0.000 claims description 6
- 210000000170 cell membrane Anatomy 0.000 claims description 6
- 230000009885 systemic effect Effects 0.000 claims description 6
- 239000003472 antidiabetic agent Substances 0.000 claims description 5
- 208000037976 chronic inflammation Diseases 0.000 claims description 5
- 230000006020 chronic inflammation Effects 0.000 claims description 5
- 108090000623 proteins and genes Proteins 0.000 claims description 5
- 102000004169 proteins and genes Human genes 0.000 claims description 5
- 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 description 4
- 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 description 4
- 241000711573 Coronaviridae Species 0.000 claims description 4
- 208000008589 Obesity Diseases 0.000 claims description 4
- 239000004480 active ingredient Substances 0.000 claims description 4
- 239000003524 antilipemic agent Substances 0.000 claims description 4
- 230000001413 cellular effect Effects 0.000 claims description 4
- 238000009109 curative therapy Methods 0.000 claims description 4
- LPTRNLNOHUVQMS-UHFFFAOYSA-N epicatechin Natural products Cc1cc(O)cc2OC(C(O)Cc12)c1ccc(O)c(O)c1 LPTRNLNOHUVQMS-UHFFFAOYSA-N 0.000 claims description 4
- 235000012734 epicatechin Nutrition 0.000 claims description 4
- 208000030159 metabolic disease Diseases 0.000 claims description 4
- 238000000034 method Methods 0.000 claims description 4
- 235000020824 obesity Nutrition 0.000 claims description 4
- 230000008569 process Effects 0.000 claims description 4
- 238000011321 prophylaxis Methods 0.000 claims description 4
- 241001529453 unidentified herpesvirus Species 0.000 claims description 4
- 208000023275 Autoimmune disease Diseases 0.000 claims description 3
- 201000003176 Severe Acute Respiratory Syndrome Diseases 0.000 claims description 3
- 229940125708 antidiabetic agent Drugs 0.000 claims description 3
- 230000004064 dysfunction Effects 0.000 claims description 3
- 230000000069 prophylactic effect Effects 0.000 claims description 3
- 108091007403 Cholesterol transporters Proteins 0.000 claims description 2
- 208000009889 Herpes Simplex Diseases 0.000 claims description 2
- 208000007514 Herpes zoster Diseases 0.000 claims description 2
- 241000700586 Herpesviridae Species 0.000 claims description 2
- 241000701027 Human herpesvirus 6 Species 0.000 claims description 2
- 241000713772 Human immunodeficiency virus 1 Species 0.000 claims description 2
- 241000713340 Human immunodeficiency virus 2 Species 0.000 claims description 2
- 241000714192 Human spumaretrovirus Species 0.000 claims description 2
- 241000713666 Lentivirus Species 0.000 claims description 2
- 241000701076 Macacine alphaherpesvirus 1 Species 0.000 claims description 2
- 241000127282 Middle East respiratory syndrome-related coronavirus Species 0.000 claims description 2
- 241000150452 Orthohantavirus Species 0.000 claims description 2
- 241000711504 Paramyxoviridae Species 0.000 claims description 2
- 208000002606 Paramyxoviridae Infections Diseases 0.000 claims description 2
- 241000710799 Rubella virus Species 0.000 claims description 2
- 241000315672 SARS coronavirus Species 0.000 claims description 2
- 239000002260 anti-inflammatory agent Substances 0.000 claims description 2
- 229940121363 anti-inflammatory agent Drugs 0.000 claims description 2
- 150000001720 carbohydrates Chemical class 0.000 claims description 2
- 208000013403 hyperactivity Diseases 0.000 claims description 2
- 230000004770 neurodegeneration Effects 0.000 claims description 2
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 2
- 230000035515 penetration Effects 0.000 claims description 2
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 2
- 230000006641 stabilisation Effects 0.000 claims description 2
- 238000011105 stabilization Methods 0.000 claims description 2
- 241001430294 unidentified retrovirus Species 0.000 claims description 2
- 201000005505 Measles Diseases 0.000 claims 1
- 208000005647 Mumps Diseases 0.000 claims 1
- 206010037742 Rabies Diseases 0.000 claims 1
- 241000725643 Respiratory syncytial virus Species 0.000 claims 1
- 230000000903 blocking effect Effects 0.000 claims 1
- 208000010805 mumps infectious disease Diseases 0.000 claims 1
- 230000019491 signal transduction Effects 0.000 claims 1
- 239000003814 drug Substances 0.000 description 16
- 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 10
- 206010035664 Pneumonia Diseases 0.000 description 9
- 230000000840 anti-viral effect Effects 0.000 description 6
- 206010061218 Inflammation Diseases 0.000 description 5
- 235000012000 cholesterol Nutrition 0.000 description 5
- 206010012601 diabetes mellitus Diseases 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 230000004054 inflammatory process Effects 0.000 description 5
- 241000894006 Bacteria Species 0.000 description 4
- 206010037660 Pyrexia Diseases 0.000 description 4
- 230000001093 anti-cancer Effects 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 230000003013 cytotoxicity Effects 0.000 description 4
- 231100000135 cytotoxicity Toxicity 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
- 230000003308 immunostimulating effect Effects 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 102100035765 Angiotensin-converting enzyme 2 Human genes 0.000 description 3
- 108090000975 Angiotensin-converting enzyme 2 Proteins 0.000 description 3
- 206010009944 Colon cancer Diseases 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 108090001074 Nucleocapsid Proteins Proteins 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 208000036142 Viral infection Diseases 0.000 description 3
- 239000003963 antioxidant agent Substances 0.000 description 3
- 235000006708 antioxidants Nutrition 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 239000003925 fat Substances 0.000 description 3
- 230000002757 inflammatory effect Effects 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 3
- BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 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 2
- 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
- BSDNZCQPDVTDET-HWKANZROSA-N (E)-3-(2-Hydroxyphenyl)-2-propenal Chemical compound OC1=CC=CC=C1\C=C\C=O BSDNZCQPDVTDET-HWKANZROSA-N 0.000 description 2
- BSDNZCQPDVTDET-UHFFFAOYSA-N 2-hydroxy cinnamaldehyde Natural products OC1=CC=CC=C1C=CC=O BSDNZCQPDVTDET-UHFFFAOYSA-N 0.000 description 2
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 2
- 102100030988 Angiotensin-converting enzyme Human genes 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 208000024172 Cardiovascular disease Diseases 0.000 description 2
- 208000035473 Communicable disease Diseases 0.000 description 2
- 229920000858 Cyclodextrin Polymers 0.000 description 2
- 206010012735 Diarrhoea Diseases 0.000 description 2
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin 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(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 2
- 208000032928 Dyslipidaemia Diseases 0.000 description 2
- 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 2
- 108010010803 Gelatin Proteins 0.000 description 2
- 208000017604 Hodgkin disease Diseases 0.000 description 2
- 241000282412 Homo Species 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
- 208000017170 Lipid metabolism disease Diseases 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 208000001145 Metabolic Syndrome Diseases 0.000 description 2
- 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 description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
- 102000003728 Peroxisome Proliferator-Activated Receptors Human genes 0.000 description 2
- 108090000029 Peroxisome Proliferator-Activated Receptors Proteins 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 230000003178 anti-diabetic effect Effects 0.000 description 2
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- 239000003443 antiviral agent Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- ADRVNXBAWSRFAJ-UHFFFAOYSA-N catechin Natural products OC1Cc2cc(O)cc(O)c2OC1c3ccc(O)c(O)c3 ADRVNXBAWSRFAJ-UHFFFAOYSA-N 0.000 description 2
- 235000005487 catechin Nutrition 0.000 description 2
- 230000005754 cellular signaling Effects 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 229950001002 cianidanol Drugs 0.000 description 2
- 208000029742 colonic neoplasm Diseases 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 229940097362 cyclodextrins Drugs 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 235000015872 dietary supplement Nutrition 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
- 238000002474 experimental method Methods 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 230000004927 fusion Effects 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 2
- -1 glycosphingolipids Chemical class 0.000 description 2
- 150000002339 glycosphingolipids Chemical class 0.000 description 2
- 230000000055 hyoplipidemic effect Effects 0.000 description 2
- 230000002218 hypoglycaemic effect Effects 0.000 description 2
- 229960001438 immunostimulant agent Drugs 0.000 description 2
- 239000003022 immunostimulating agent Substances 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 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 description 2
- 102000004311 liver X receptors Human genes 0.000 description 2
- 108090000865 liver X receptors Proteins 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
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 230000035778 pathophysiological process Effects 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 239000003016 pheromone Substances 0.000 description 2
- 230000035790 physiological processes and functions Effects 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 230000000241 respiratory effect Effects 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 229960005486 vaccine Drugs 0.000 description 2
- 230000009385 viral infection Effects 0.000 description 2
- 230000003612 virological effect Effects 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 238000001262 western blot Methods 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
- 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 1
- SWLAMJPTOQZTAE-UHFFFAOYSA-N 4-[2-[(5-chloro-2-methoxybenzoyl)amino]ethyl]benzoic acid Chemical class COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(C(O)=O)C=C1 SWLAMJPTOQZTAE-UHFFFAOYSA-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
- 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 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 208000010507 Adenocarcinoma of Lung Diseases 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 208000010470 Ageusia Diseases 0.000 description 1
- 229940077274 Alpha glucosidase inhibitor Drugs 0.000 description 1
- 206010061424 Anal cancer Diseases 0.000 description 1
- 206010002653 Anosmia Diseases 0.000 description 1
- 208000007860 Anus Neoplasms Diseases 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- QRGLVSPIIXTSIE-UHFFFAOYSA-N BCA Natural products O=CC=CC1=CC=CC=C1OC(=O)C1=CC=CC=C1 QRGLVSPIIXTSIE-UHFFFAOYSA-N 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 229940123208 Biguanide Drugs 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- 208000011691 Burkitt lymphomas Diseases 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- 208000025721 COVID-19 Diseases 0.000 description 1
- 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 description 1
- 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 description 1
- 206010007953 Central nervous system lymphoma Diseases 0.000 description 1
- 206010008342 Cervix carcinoma Diseases 0.000 description 1
- 229920001268 Cholestyramine Polymers 0.000 description 1
- 208000014085 Chronic respiratory disease Diseases 0.000 description 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 206010011224 Cough Diseases 0.000 description 1
- 208000028399 Critical Illness Diseases 0.000 description 1
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 1
- 208000007342 Diabetic Nephropathies Diseases 0.000 description 1
- 239000001692 EU approved anti-caking agent Substances 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 206010015150 Erythema Diseases 0.000 description 1
- 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 description 1
- 208000010201 Exanthema Diseases 0.000 description 1
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
- 208000001034 Frostbite Diseases 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
- 206010017533 Fungal infection Diseases 0.000 description 1
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 1
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 1
- 208000022072 Gallbladder Neoplasms Diseases 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 108010024636 Glutathione Proteins 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
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 208000021519 Hodgkin lymphoma Diseases 0.000 description 1
- 208000010747 Hodgkins lymphoma Diseases 0.000 description 1
- 101000638154 Homo sapiens Transmembrane protease serine 2 Proteins 0.000 description 1
- 241000725303 Human immunodeficiency virus Species 0.000 description 1
- 208000031226 Hyperlipidaemia Diseases 0.000 description 1
- 206010021024 Hypolipidaemia Diseases 0.000 description 1
- 206010053574 Immunoblastic lymphoma Diseases 0.000 description 1
- 206010062016 Immunosuppression Diseases 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- 208000007766 Kaposi sarcoma Diseases 0.000 description 1
- 208000008839 Kidney Neoplasms Diseases 0.000 description 1
- 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 description 1
- 239000005551 L01XE03 - Erlotinib Substances 0.000 description 1
- 239000002147 L01XE04 - Sunitinib 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
- 241000712902 Lassa mammarenavirus Species 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- 241001115401 Marburgvirus Species 0.000 description 1
- 241000712079 Measles morbillivirus Species 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 208000003445 Mouth Neoplasms Diseases 0.000 description 1
- 208000034578 Multiple myelomas Diseases 0.000 description 1
- 241000711386 Mumps virus Species 0.000 description 1
- 208000031888 Mycoses Diseases 0.000 description 1
- 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 description 1
- 206010028735 Nasal congestion Diseases 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 102000007399 Nuclear hormone receptor Human genes 0.000 description 1
- 108020005497 Nuclear hormone receptor Proteins 0.000 description 1
- 229940122313 Nucleoside reverse transcriptase inhibitor Drugs 0.000 description 1
- 206010068319 Oropharyngeal pain Diseases 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
- 208000030852 Parasitic disease Diseases 0.000 description 1
- 201000007100 Pharyngitis Diseases 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 229940079156 Proteasome inhibitor Drugs 0.000 description 1
- 229940096437 Protein S Drugs 0.000 description 1
- 241000711798 Rabies lyssavirus Species 0.000 description 1
- 208000015634 Rectal Neoplasms Diseases 0.000 description 1
- 206010038389 Renal cancer Diseases 0.000 description 1
- 108091006197 SARS-CoV-2 Nucleocapsid Protein Proteins 0.000 description 1
- 101710198474 Spike protein Proteins 0.000 description 1
- 229930182558 Sterol Natural products 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- CBPNZQVSJQDFBE-FUXHJELOSA-N Temsirolimus Chemical compound C1C[C@@H](OC(=O)C(C)(CO)CO)[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 CBPNZQVSJQDFBE-FUXHJELOSA-N 0.000 description 1
- 208000024313 Testicular Neoplasms Diseases 0.000 description 1
- 206010057644 Testis cancer Diseases 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 102100031989 Transmembrane protease serine 2 Human genes 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- 208000002495 Uterine Neoplasms Diseases 0.000 description 1
- 102100026383 Vasopressin-neurophysin 2-copeptin Human genes 0.000 description 1
- JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 1
- 108070000030 Viral receptors Proteins 0.000 description 1
- 229930003268 Vitamin C Natural products 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- QRGLVSPIIXTSIE-UXBLZVDNSA-N [2-[(e)-3-oxoprop-1-enyl]phenyl] benzoate Chemical compound O=C\C=C\C1=CC=CC=C1OC(=O)C1=CC=CC=C1 QRGLVSPIIXTSIE-UXBLZVDNSA-N 0.000 description 1
- 238000002835 absorbance Methods 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
- 230000001154 acute effect Effects 0.000 description 1
- 230000033289 adaptive immune response Effects 0.000 description 1
- 229960001686 afatinib Drugs 0.000 description 1
- 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 description 1
- 239000008272 agar Substances 0.000 description 1
- 235000019666 ageusia Nutrition 0.000 description 1
- 230000032683 aging Effects 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
- 229940100198 alkylating agent Drugs 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 239000003888 alpha glucosidase inhibitor Substances 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 239000010775 animal oil Substances 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 230000002924 anti-infective effect Effects 0.000 description 1
- 230000000340 anti-metabolite Effects 0.000 description 1
- 239000003416 antiarrhythmic agent Substances 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 239000003793 antidiarrheal agent Substances 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 229940100197 antimetabolite Drugs 0.000 description 1
- 239000002256 antimetabolite Substances 0.000 description 1
- 229940045988 antineoplastic drug protein kinase inhibitors Drugs 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 201000011165 anus cancer Diseases 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 239000000305 astragalus gummifer gum Substances 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 229960000397 bevacizumab Drugs 0.000 description 1
- 150000004283 biguanides Chemical class 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 238000002725 brachytherapy Methods 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 210000003123 bronchiole Anatomy 0.000 description 1
- 229960002092 busulfan Drugs 0.000 description 1
- 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 description 1
- 235000008207 calcium folinate Nutrition 0.000 description 1
- 239000011687 calcium folinate Substances 0.000 description 1
- 229960004117 capecitabine Drugs 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 235000010418 carrageenan Nutrition 0.000 description 1
- 239000000679 carrageenan Substances 0.000 description 1
- 229920001525 carrageenan Polymers 0.000 description 1
- 229940113118 carrageenan Drugs 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 238000012200 cell viability kit Methods 0.000 description 1
- 201000010881 cervical cancer Diseases 0.000 description 1
- 229960005395 cetuximab Drugs 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 229960004630 chlorambucil Drugs 0.000 description 1
- JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 description 1
- 108010011793 cholesterol binding protein Proteins 0.000 description 1
- 102000049842 cholesterol binding protein Human genes 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 208000020832 chronic kidney disease Diseases 0.000 description 1
- 208000022831 chronic renal failure syndrome Diseases 0.000 description 1
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
- 229960004316 cisplatin Drugs 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 229940099112 cornstarch Drugs 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- 229960004397 cyclophosphamide Drugs 0.000 description 1
- 229960000975 daunorubicin Drugs 0.000 description 1
- 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 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 201000010064 diabetes insipidus Diseases 0.000 description 1
- 208000033679 diabetic kidney disease Diseases 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000003968 dna methyltransferase inhibitor Substances 0.000 description 1
- 229960003668 docetaxel Drugs 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 229960004679 doxorubicin Drugs 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 230000012202 endocytosis Effects 0.000 description 1
- 229960001433 erlotinib Drugs 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
- 231100000321 erythema Toxicity 0.000 description 1
- 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 description 1
- 229960005420 etoposide Drugs 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 229960005167 everolimus Drugs 0.000 description 1
- 201000005884 exanthem Diseases 0.000 description 1
- 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 description 1
- 229960000815 ezetimibe Drugs 0.000 description 1
- 229940125753 fibrate Drugs 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 229960002949 fluorouracil Drugs 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 229960002737 fructose Drugs 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 201000010175 gallbladder cancer Diseases 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 229960000578 gemtuzumab Drugs 0.000 description 1
- 208000004104 gestational diabetes Diseases 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229960001031 glucose Drugs 0.000 description 1
- 229960003180 glutathione Drugs 0.000 description 1
- 235000003969 glutathione Nutrition 0.000 description 1
- 229930004094 glycosylphosphatidylinositol Natural products 0.000 description 1
- 235000010417 guar gum Nutrition 0.000 description 1
- 239000000665 guar gum Substances 0.000 description 1
- 229960002154 guar gum Drugs 0.000 description 1
- 229920000591 gum Polymers 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 1
- 108091006093 heterotrimeric G proteins Proteins 0.000 description 1
- 102000034345 heterotrimeric G proteins Human genes 0.000 description 1
- 229940121372 histone deacetylase inhibitor Drugs 0.000 description 1
- 239000003276 histone deacetylase inhibitor Substances 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 239000002955 immunomodulating agent Substances 0.000 description 1
- 229940121354 immunomodulator Drugs 0.000 description 1
- 230000001506 immunosuppresive effect Effects 0.000 description 1
- 238000009169 immunotherapy Methods 0.000 description 1
- 239000000859 incretin Substances 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000015788 innate immune response Effects 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 229940124524 integrase inhibitor Drugs 0.000 description 1
- 239000002850 integrase inhibitor Substances 0.000 description 1
- 229940047124 interferons Drugs 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 201000010982 kidney cancer Diseases 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 208000012987 lip and oral cavity carcinoma Diseases 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 201000007270 liver cancer Diseases 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 201000005249 lung adenocarcinoma Diseases 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 229950004994 meglitinide Drugs 0.000 description 1
- 229960001924 melphalan Drugs 0.000 description 1
- SGDBTWWWUNNDEQ-LBPRGKRZSA-N melphalan Chemical compound OC(=O)[C@@H](N)CC1=CC=C(N(CCCl)CCCl)C=C1 SGDBTWWWUNNDEQ-LBPRGKRZSA-N 0.000 description 1
- 210000002284 membrane microdomain Anatomy 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- 244000000010 microbial pathogen Species 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 239000011859 microparticle Substances 0.000 description 1
- 229960004857 mitomycin Drugs 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
- 210000001616 monocyte Anatomy 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 206010061311 nervous system neoplasm Diseases 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 239000011664 nicotinic acid Substances 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
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 235000021590 normal diet Nutrition 0.000 description 1
- 108020004017 nuclear receptors Proteins 0.000 description 1
- 150000003833 nucleoside derivatives Chemical class 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 231100000590 oncogenic Toxicity 0.000 description 1
- 230000002246 oncogenic effect Effects 0.000 description 1
- 239000002357 osmotic agent Substances 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 230000036542 oxidative stress Effects 0.000 description 1
- 238000002640 oxygen therapy Methods 0.000 description 1
- 201000002528 pancreatic cancer Diseases 0.000 description 1
- 208000008443 pancreatic carcinoma Diseases 0.000 description 1
- 229960005489 paracetamol Drugs 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 244000045947 parasite Species 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 229940068065 phytosterols Drugs 0.000 description 1
- MXXWOMGUGJBKIW-YPCIICBESA-N piperine Chemical compound C=1C=C2OCOC2=CC=1/C=C/C=C/C(=O)N1CCCCC1 MXXWOMGUGJBKIW-YPCIICBESA-N 0.000 description 1
- 229940075559 piperine Drugs 0.000 description 1
- WVWHRXVVAYXKDE-UHFFFAOYSA-N piperine Natural products O=C(C=CC=Cc1ccc2OCOc2c1)C3CCCCN3 WVWHRXVVAYXKDE-UHFFFAOYSA-N 0.000 description 1
- 235000019100 piperine Nutrition 0.000 description 1
- 229920000058 polyacrylate Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229940068917 polyethylene glycols Drugs 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
- 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 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 239000003805 procoagulant Substances 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 239000003207 proteasome inhibitor Substances 0.000 description 1
- 239000003909 protein kinase inhibitor Substances 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 206010037844 rash Diseases 0.000 description 1
- 206010038038 rectal cancer Diseases 0.000 description 1
- 201000001275 rectum cancer Diseases 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 108090000064 retinoic acid receptors Proteins 0.000 description 1
- 102000003702 retinoic acid receptors Human genes 0.000 description 1
- 239000003419 rna directed dna polymerase inhibitor Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 150000003408 sphingolipids Chemical class 0.000 description 1
- 102000009076 src-Family Kinases Human genes 0.000 description 1
- 108010087686 src-Family Kinases Proteins 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 150000003432 sterols Chemical class 0.000 description 1
- 235000003702 sterols Nutrition 0.000 description 1
- 201000011549 stomach cancer Diseases 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- 229960001796 sunitinib Drugs 0.000 description 1
- WINHZLLDWRZWRT-ATVHPVEESA-N sunitinib Chemical compound CCN(CC)CCNC(=O)C1=C(C)NC(\C=C/2C3=CC(F)=CC=C3NC\2=O)=C1C WINHZLLDWRZWRT-ATVHPVEESA-N 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 238000002636 symptomatic treatment Methods 0.000 description 1
- 210000000225 synapse Anatomy 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 229960000235 temsirolimus Drugs 0.000 description 1
- QFJCIRLUMZQUOT-UHFFFAOYSA-N temsirolimus Natural products C1CC(O)C(OC)CC1CC(C)C1OC(=O)C2CCCCN2C(=O)C(=O)C(O)(O2)C(C)CCC2CC(OC)C(C)=CC=CC=CC(C)CC(C)C(=O)C(OC)C(O)C(C)=CC(C)C(=O)C1 QFJCIRLUMZQUOT-UHFFFAOYSA-N 0.000 description 1
- 201000003120 testicular cancer Diseases 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 108091005703 transmembrane proteins Proteins 0.000 description 1
- 102000035160 transmembrane proteins Human genes 0.000 description 1
- 229960000575 trastuzumab Drugs 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 229940121358 tyrosine kinase inhibitor Drugs 0.000 description 1
- 239000005483 tyrosine kinase inhibitor Substances 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- 206010046766 uterine cancer Diseases 0.000 description 1
- 238000002255 vaccination Methods 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 229960003862 vemurafenib Drugs 0.000 description 1
- GPXBXXGIAQBQNI-UHFFFAOYSA-N vemurafenib Chemical compound CCCS(=O)(=O)NC1=CC=C(F)C(C(=O)C=2C3=CC(=CN=C3NC=2)C=2C=CC(Cl)=CC=2)=C1F GPXBXXGIAQBQNI-UHFFFAOYSA-N 0.000 description 1
- 229960003048 vinblastine Drugs 0.000 description 1
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1
- 229960004528 vincristine Drugs 0.000 description 1
- 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 description 1
- 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 description 1
- 239000011718 vitamin C Substances 0.000 description 1
- 235000019154 vitamin C Nutrition 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 229940100445 wheat starch Drugs 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 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
- A61K31/01—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
- A61K31/56—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
- 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
- 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
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- 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
- A61P31/04—Antibacterial agents
-
- 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
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
-
- 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
- A61P31/14—Antivirals for RNA viruses
- A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
-
- 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
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
-
- 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
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Virology (AREA)
- Diabetes (AREA)
- Communicable Diseases (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Oncology (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Molecular Biology (AREA)
- Immunology (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Tropical Medicine & Parasitology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Child & Adolescent Psychology (AREA)
- Transplantation (AREA)
- Pulmonology (AREA)
- AIDS & HIV (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明涉及一种药物组合物，所述药物组合物可用作包膜病原体及其各种并发症的一种抗感染药物。
Description
技术领域
本发明涉及一种药物组合物，所述药物组合物可用作包膜病原体、特别是冠状病毒及其各种并发症的抗感染药。
背景技术
新冠肺炎是一种新兴的大规模传染病，被称为Covid-19，该传染病由冠状病毒SARS-CoV-2引起的。新冠肺炎的发病机制非常多样化，受感染的个体不一定会出现症状。现有文献中提到，新冠肺炎最常见的表现是呼吸道感染的一些典型症状:发烧、咳嗽，以及由于细支气管内液体积累引起的呼吸道不适。其他不太系统的症状因年龄而异，包括头痛、不适、反复跌倒或意识模糊、鼻塞、喉咙痛、恶心、呕吐、腹泻、味觉丧失、嗅觉丧失、红斑、皮疹，以及不太常见的冻伤。
所述疾病的治疗旨在缓解发病症状，例如：使用止痛药，如治疗发烧和腹泻的对乙酰氨基酚和抗腹泻药物、让病人在感染期间休息、补充水分以避免因发烧和疼痛而脱水。此外，除了对症治疗之外，还可以实施氧疗、进行血栓预防、使用抗心律失常药物、使用抗凝剂或进行透析。
此外，许多项目正在开展中，以更好地了解这种病毒及其引起的疾病，并确定新的治疗目标。这使得制定新的治疗策略成为可能：
疫苗接种:新冠肺炎疫苗的到来为抗击冠状病毒SARS-CoV-2感染带来了极大的希望。但从长远来看，疫苗对冠状病毒SARS-CoV-2及其变种的效果如何还是个未知数。
血浆疗法:从康复的病人身上提取血浆，以类似疫苗的方式给那些重症患者使用。
免疫疗法:该疗法的目标是使用抗体类药物，以防止有发展成新冠肺炎重症风险的患者住院，特别是那些患有心血管疾病、慢性呼吸系统疾病、肥胖、糖尿病、慢性肾功能衰竭以及艾滋病毒或癌症相关的免疫抑制等共病症的患者。然而，许多关于免疫原性、特异性、安全性和治疗潜力的问题仍然没有答案。
现下，没有可以单独治愈新冠肺炎感染的治疗方法。 使用免疫刺激剂、抗病毒药物和抗氧化剂可能有助于降低感染新冠肺炎的风险。
在这种感染情况下，细胞膜在许多生理或病理生理过程中起到重要作用。事实上，它包含了细胞与其环境之间进行交换的大部分基本要素。细胞膜由膜微区，即脂筏组成。膜微区由脂质(鞘糖脂和/或鞘磷脂和胆固醇)和蛋白质(糖基磷脂酰肌醇锚定蛋白、胆固醇结合蛋白、跨膜蛋白、双乙酰化Src家族酪氨酸激酶、异源三聚体G蛋白的α亚基)紧密组合而成。所述胆固醇起着动态“粘合剂”的作用，它赋予这些膜微区刚性和结构。所述蛋白质，包括ACE2、TMPRSS2和许多其他受体，在细胞信号传导中起着关键作用，并参与一些炎症和感染过程，以及参与到代谢紊乱和致癌进程之中。此外，病原体或内源性信号激活了所述细胞膜，其中伴随出现的功能障碍或结构变化可能会导致微粒过量，所述微粒过量会导致炎症加重、全身性免疫过度激活、易凝血，引起心血管疾病、并使其进一步发展、恶化，所述心血管疾病包括动脉粥样硬化、心肌梗塞、中风以及癌症。
病毒性炎症被认为是代谢综合症疾病的重要原因，特别是在冠状病毒SARS-CoV-2感染对象更是如此。
此外，d-柠檬烯因其抗菌和抗病毒潜力而闻名。它还具有抗糖尿病和降血脂的特性，因此可以被认为是预防和治疗感染性疾病中常出现的代谢紊乱疾病的潜在药物。d-柠檬烯的抗氧化、抗炎和抗癌特性是众所周知的。在人体中，d-柠檬烯在一次剂量后显示出低毒性，毒性持续一年以上。
β-谷甾醇和羽扇豆醇是分子结构类似于胆固醇的植物甾醇。在这方面，他们可以与后者相较量。β-谷甾醇和羽扇豆醇在植物中的作用与胆固醇在人体中的作用相同，即维持细胞膜的结构和功能。大量科学数据表明，这两个甾醇具有降血糖、降血脂、抗炎、解热、用作免疫刺激剂和抗癌的特性。 β-谷甾醇和羽扇豆醇可以通过限制刺突蛋白粘附到受体血管紧张素转化酶2（ACE2）上，来抑制冠状病毒SARS-CoV-2进入细胞。它们的药理学潜力使它们成为代谢综合征疾病和磷脂双分子层病原体传染的治疗剂。
肉桂醛因其降血糖、降血脂和抗癌特性而为人所知。其抗细菌、抗真菌、免疫刺激和抗病毒特性是已知的。
要解决的技术问题
本发明的一个目的是提供一种新的药物组合物，所述药物组合物可用作药物，更具体地，适合用于治疗包膜病原体引起的感染、疾病及其并发症。
本发明的另一个目的是提供一种新的药物组合物，所述药物组合物可用作药物，更具体地，可用于治疗疾病以弥补上述背景技术中提到的与所述组合物相关的全部或部分缺点。
本发明的另一个目的是提供一种药物组合物，所述药物组合物可用作药物，具体地，可以用于糖尿病、血脂异常和肥胖症的治疗。
本发明的另一个目的是提供一种药物组合物，所述药物组合物可以抑制患有合并症的患者的循环单核细胞、巨噬细胞、白细胞和胰腺细胞的炎症表型。
本发明的另一个目的是提供一种药物组合物，所述药物组合物会减少甚至会抑制病原体(如病毒、细菌、寄生虫等)进入它们的目标细胞。
本发明的另一个目的是提供一种药物组合物，所述药物组合物可以限制或甚至抑制细胞中冠状病毒SARS-CoV-2和其不同变体的传染性，可以抑制病毒的复制，并激活适当的免疫反应。
本发明的另一个目的是提供一种药物组合物，具体是如上所述的药物组合物，其毒性降低和/或为患者可承受的程度。
发明概述
为了解决上述技术问题中的至少一个，本发明提出了一种药物组合物，其特征在于，包含活性成分d-柠檬烯、羽扇豆醇、β-谷甾醇、肉桂醛，以及可选的儿茶素、姜黄素及其组合物。
申请人确实发现所述药物组合物对病毒、细菌、真菌和寄生虫的感染有效。
申请人还证明了一种协同效应，即本发明所述的药物组合物通过抑制慢性炎症和全身性免疫过度激活以及抑制病原体进入宿主细胞增强了对背景技术中提及的疾病的效果。
申请人还发现，本发明的组合物对与新冠肺炎相关的各种并发症具有预防作用。
发明内容
根据本发明，所述药物组合物可用作药物，更具体地，用于包膜病原体感染及其各种并发症的预防性和治愈性治疗。
基于本发明的特定制造方法，所述药物组合物可进一步包含d-柠檬烯、羽扇豆醇、β-谷甾醇、肉桂醛的混合物；或d-柠檬烯、羽扇豆醇、β-谷甾醇、肉桂醛和表没食子儿茶素没食子酸酯(EGCG)的混合物；或d-柠檬烯、羽扇豆醇、β-谷甾醇、肉桂醛和姜黄素的混合物；或d-柠檬烯、羽扇豆醇、β-谷甾醇、肉桂醛、表没食子儿茶素没食子酸酯(EGCG)和姜黄素的混合物。
例如，所述药物组合物包含，作为活性成分总质量的加权百分比基本上等于或高于10重量百分比，且基本上等于或低于55重量百分比的所述d-柠檬烯，具体地，所述d-柠檬烯含量为基本上等于或高于20重量百分比且基本上等于或低于40重量百分比。
所述羽扇豆醇的比例基本上等于或高于15%，且基本上等于或低于55%，具体地，所述羽扇豆醇基本上等于或高于30%，且基本上等于或低于40%。
所述β-谷甾醇的比例基本上等于或高于10%，且基本上等于或低于45%，具体地，所述β-谷甾醇基本上等于或高于15%且基本上等于或低于30%。
所述肉桂醛的比例基本上等于或高于15%，且基本上等于或低于45%，具体地， 所述肉桂醛基本上等于或高于20%，且基本上等于或低于40%。
所述表没食子儿茶素没食子酸酯(EGCG)的比例基本上等于或高15%，且基本上等于或低于40%，具体地，所述表没食子儿茶素没食子酸酯(EGCG)基本上等于或高于25%，且基本上等于或低于35%。
所述姜黄素的比例基本上等于或高于15 %，且基本上等于或低于40%，具体地，所述姜黄素基本上等于或高于25 %，且基本上等于或低于35 %。
本发明所述的药物组合物还包含至少一种药学上可接受的赋形剂。所述赋形剂可以是固体或者液体。所述赋形剂可以选自例如纯净水、乙醇、丙二醇、甘油、植物油、动物油、烃、硅氧树脂、糖如葡萄糖、环糊精、左旋糖、小麦淀粉、玉米淀粉、马铃薯淀粉、黄原胶、阿拉伯胶、黄蓍胶、苹婆胶、瓜尔胶（Guaranates）、果胶、海藻酸胶、卡拉胶、琼脂（Agar-Agar）、明胶、纤维素及其衍生物。
本发明所述的药物组合物可以通过任何合适的途径给药，例如口服，或在如下部位给药：直肠、局部（如局部外用)、腹膜内、全身、静脉内、肌内、皮下或粘膜，尤其是舌下给药，或者使用贴剂，或者将药物包封或固定在脂质体、微粒、微胶囊、纳米颗粒等之上。适用于口服给药的赋形剂的非限制性例子包括滑石、乳糖、淀粉及其衍生物、纤维素及其衍生物、环糊精、胡椒碱、聚乙二醇、丙烯酸聚合物、明胶、硬脂酸镁、动物脂肪、植物脂肪或合成脂肪、石蜡衍生物、乙二醇、稳定剂、防腐剂、抗氧化剂、湿润剂、抗结块剂、分散剂、乳化剂、味道改良剂、渗透剂、增溶剂。药物和药物组合物的配制和给药技术是众所周知的，技术人员尤其可以参考书籍《雷明顿药物科学》最新版。
基于本发明，优选地，所述组合物适宜口服或静脉注射给药。
根据本发明，优选地，所述组合物适宜以等于或高于40 mg/kg/24h,且等于或低于200 mg/kg/24h的剂量，口服或静脉注射一剂或多剂给有此需要的哺乳动物。
例如，本发明所述的药物组合物可以用于由包膜病原体引起的感染的预防性和/或治愈性治疗。
根据本发明，优选地，所述药物组合物可用于治疗慢性炎性和/或由碳水化合物失衡和/或脂质失衡和/或细胞胆固醇转运蛋白功能障碍和/或严重急性呼吸综合征和/或全身性免疫过度激活引起的慢性炎性的治疗，特别适用于感染了包膜病原体的患者和合并症患者中。
在被具有磷脂双分子层包膜的病原体(例如SARS- Cov-2)感染的情况下，申请人已经表明，本发明所述的药物组合物至少在体外表现良好，并且显示出低细胞毒性。
本发明所述药物组合物的作用机制还没有完全阐明。很有可能的是，所述药物组合物同时作用于导致背景技术中所述疾病的各种机制。所述药物组合物被认为通过对核受体，特别是过氧化物酶体增殖物活化受体（PPARs）、肝X受体（LXRs）和视黄酸受体（RXRs）进行协同调节发挥作用，从而使得细胞和膜胆固醇流出，抑制一些鞘脂，特别是鞘糖脂，还有一些膜蛋白，特别是血管紧张素转化酶2（ACE2）的过表达，并抑制促炎细胞因子的产生。还认为所述药物组合物通过免疫刺激发挥作用。
此外，根据本发明，所述组合物分解并重构了细胞的脂质组成，特别是细胞膜脂筏(包膜病原体的靶标)的脂质组成,因此可以防止这些微区的稳定、融合复合物的建立、突触的形成、内吞作用，从长远来看，从而防止所述包膜病原体渗透入细胞。
此外，所述膜微区的脂质组成的改变导致构象变化，和在其中发现的蛋白质(特别是病毒受体、G蛋白偶联受体)的功能性活动或功能异常性活动的改变，并最终导致许多病理生理过程中涉及的细胞信号传导途径的改变，所述病理生理过程包括病原体引发的感染、癌症、肥胖症、代谢性疾病、自身免疫性疾病和神经退行性疾病。
这种脂质的分解也可以发生在病原体的包膜中，改变感染过程中涉及的信息蛋白的构象，以及所述信息蛋白与靶细胞的结合。这种机制被认为适用于具有与其靶细胞相似的生物物理和生物化学特性的病毒、细菌上，特别在所述磷脂双分子层包膜水平。
根据本发明，有利地，所述药物组合物可用于降低或抑制病原体及其变体的耐药性、细胞的炎症表型、氧化应激和免疫细胞的衰老，并增加先天和适应性免疫反应。
此外，根据本发明，所述药物组合物可用于治疗由包膜病原体及其变体引起的感染，特别是冠状病毒科(SARS- CoV，MERS-CoV，SARS-CoV-2)，疱疹病毒科(单纯疱疹，水痘带状疱疹，人类疱疹病毒第四型（EBV），人类疱疹病毒6至7型（HHV-6 to 7）、疱疹病毒B)、逆转录病毒(慢病毒属，包括HIV-1病毒和HIV-2病毒、肿瘤病毒和泡沫病毒)、粘病毒、副粘病毒科(副流感病毒、腮腺炎病毒、麻疹病毒、呼吸道合胞病毒)、狂犬病病毒、拉沙病毒、汉坦病毒、马尔堡病毒、风疹病毒)以及用于治疗癌症。
这些包括卡波西肉瘤、伯基特氏淋巴瘤、免疫母细胞性淋巴瘤、脑淋巴瘤、原发性、非霍奇金恶性淋巴瘤(NHML)、宫颈癌、口腔癌、胃癌、结肠癌，特别是浸润性结肠或结肠直肠癌、直肠癌、肛门癌、肝癌、肝细胞癌、胆囊癌、胰腺癌、肺癌，特别是肺腺癌、慢性或急性形式的白血病、多发性骨髓瘤、霍奇金淋巴瘤、脑肿瘤和其他神经系统肿瘤、膀胱癌、卵巢癌、子宫癌、睾丸癌、肾癌。
本发明还涉及一种药物制剂，包含本发明所述的药物组合物，此外，还包含混合或单独包装的至少一种抗炎剂和/或抗糖尿病剂和/或降脂剂和/或抗感染剂和/或抗癌剂，用于同时、依次或按时间间隔治疗由病原体引起的感染及其并发症。
例如，所述抗糖尿病剂可以选自双胍类药物、降血糖磺胺类药物和格列奈类药物、α-葡萄糖苷酶抑制剂、包括胰高血糖素样肽-1（GLP-1）的肠促胰岛素、胰岛素；降脂剂可以选自他汀类药物、贝特类、依泽替米贝、烟酸、消胆胺；抗病毒剂可以选自核苷或非核苷类逆转录酶抑制剂、蛋白酶抑制剂、融合抑制剂和整合酶抑制剂；所述抗癌剂可以选自抗代谢物(氨甲蝶呤、卡培他滨、5-氟尿嘧啶)、烷化剂(顺铂、丝裂霉素C、白消安) 和相关药剂(美法仑、苯丁酸氮芥、环磷酰胺)、作用于有丝分裂纺锤体的化合物(长春碱1、长春新碱、多西他赛)、酪氨酸激酶抑制剂(阿法替尼、厄洛替尼、舒尼替尼)、苏氨酸酶蛋白激酶抑制剂(维罗非尼、依维莫司、替西罗莫司)、作用于拓扑异构酶的药剂(柔红霉素、阿霉素、依托泊苷)、蛋白酶体抑制剂、DNA甲基转移酶抑制剂、组蛋白脱乙酰酶抑制剂、免疫调节剂(干扰素、皮质类固醇、talimogene)、单克隆抗体(西妥昔单抗、吉妥珠单抗、曲妥珠单抗、贝伐单抗、利妥珠单抗)，优先作用于一些靶向癌细胞的基因修饰病毒、谷胱甘肽、维生素C、亚叶酸钙及其混合物，特别是两种所述抗癌剂的混合物、适用于近距离放射疗法的放射性剂和/或可注射或可摄取的活性代谢物。
本发明还涉及一种药物制剂，包含所述d-柠檬烯、所述羽扇豆醇、所述β-谷甾醇、所述肉桂醛和任选的所述表儿茶素、所述姜黄素及其组合混合物。
本发明还涉及一种膳食补充剂，包含所述d-柠檬烯、和/或所述羽扇豆醇、和/或所述β-谷甾醇、和/或所述肉桂醛、和/或所述表儿茶素、和/或所述姜黄素的组合。
定义
术语“治疗性处理”是指治愈性和预防性处理；在本发明的含义中，治疗性处理通过发挥药理学、免疫学或代谢作用，至少部分恢复、至少部分纠正或至少部分改变生理功能。
术语“患者”指哺乳动物或人类。根据本发明，所述药物组合物也可以用于兽医学。
术语“糖尿病患者”是指一型糖尿病患者、二型糖尿病患者、女性妊娠糖尿病患者、尿崩症患者和糖尿病肾病患者。
术语“血脂异常”是指由目前的标准确定的高脂血症和低脂血症。
术语“炎症”指的是机体在遭受攻击时所引发的一系列反应。炎症可以是外源性的，如受伤、感染、创伤，也可以是身体内部原因，如自身免疫性疾病。
在本发明的含义中，“抗癌剂”是一种至少表现出体外对抗癌细胞作用的成分，无论其作用机制如何。在本发明的含义中，“作用”是指破坏或至少部分修饰癌细胞，这使得特别是限制癌细胞的增殖和/或扩散成为可能。
术语“感染”是指微生物，更准确地说是病原微生物如细菌或病毒对生物体的入侵，这种入侵需要宿主，最常见的宿主是细胞，入侵的细菌或病毒会利用细胞成分进行繁殖。
本发明所用的“膳食补充剂”是一种食品，其目的是补充正常膳食，并且是营养物或其它物质的浓缩来源，单独或组合服用具有营养或生理效果。
关于所提及的抗炎剂和/或抗糖尿病剂和/或降脂剂和/或抗感染剂和/或抗癌剂，除非另有说明，所用术语包括所指的化合物的结构异构体、构象立体异构体、对映异构体和非对映异构体。
关于本发明所述组合物中的肉桂醛(CA)，除非另有说明，该术语包括其衍生物，特别是2-羟基肉桂醛(HCA)，2′-苯甲酰氧基肉桂醛(BCA)，以及形成的二聚体，特别是HCA-HCA，BCA-BCA，CA-CA。
关于本发明组合物中的表儿茶素，除非另有说明，该术语包括其衍生物，包括儿茶素、没食子儿茶精(GC)、表儿茶素没食子酸酯(ECG)、表没食子儿茶素(EGC)、表没食子儿茶素没食子酸酯(EGCG)。
关于本发明组合物中的姜黄素，除非另有说明，该术语包括其各种合成类似物。
实验
以下组成的百分比是相对于活性成分总质量的质量百分比。
药物组合物1a: d-柠檬烯(50%)、羽扇豆醇(20%)、β-谷甾醇(20%)、肉桂醛(10%)。
药物组合物1b: d-柠檬烯(40%)、羽扇豆醇(20%)、β-谷甾醇(30%)、肉桂醛(10%)。
药物组合物1b: d-柠檬烯(40%)、羽扇豆醇(10%)、β-谷甾醇(10%)、肉桂醛(10%)、EGCG（30%）。
药物组合物1b: d-柠檬烯(50%)、羽扇豆醇(10%)、β-谷甾醇(10%)、肉桂醛(10%)、EGCG（20%）。
药物组合物1b: d-柠檬烯(40%)、羽扇豆醇(10%)、β-谷甾醇(10%)、肉桂醛(10%)、EGCG（30%）。
药物组合物1b: d-柠檬烯(50%)、羽扇豆醇(10%)、β-谷甾醇(10%)、肉桂醛(10%)、EGCG（20%）。
实验结果
分三步评估所述药物组合物在Vero E6/Vero-81细胞上的抗病毒活性:
第一步:测定6种分子和3种组合物的细胞毒性。
通过MTS细胞活性分析试剂盒来测定细胞毒性，方法如下：基于新型的四唑盐类化合物MTS与新陈代谢活跃的活细胞的生物还原反应形成有色的甲䐶，甲䐶产物的量可以通过其在490-500 nm波长处的吸光度来测量确定。与未处理细胞相比，甲䐶产物的量与培养物中活细胞的数量成正比。将制剂的浓度增加，培养24小时后，再测量细胞存活率。
第二步：高浓度组合物的抗病毒活性测定。
所述组合物将在Vero E6/Vero-81细胞上进行体外三次测试。将最高无毒性剂量的所述制剂将与受冠状病毒SARS-CoV-2感染的Vero E6/Vero-81细胞接触。在37℃下培养16小时后，细胞将被裂解，并且通过在蛋白质印迹法中发现的冠状病毒SARS-CoV-2核衣壳蛋白来证明病毒感染。核衣壳蛋白的量将通过一个公共的图像处理软件Image J进行测量确定。
通过/不通过:如果发现某些制剂在高浓度下没有抑制作用，它们则不被包括在第三步中。
第三步:测定制剂的抑制浓度50 (半抑制浓度IC50)
将在体外对感染了冠状病毒SARS-CoV-2的Vero E6/ Vero-81细胞进行三次测试，测试所述组合物的抗病毒活性。将所述药物组合物与被冠状病毒SARS-CoV-2感染的VeroE6/Vero-81细胞接触，所述药物组合物剂量逐渐增加。在37℃下培养16小时后，细胞将被裂解，并且通过在蛋白质印迹法中发现的核衣壳蛋白来证明病毒感染。核衣壳蛋白的量将通过公共的图像处理软件Image J进行测量确定。将绘制剂量反应曲线并确定半抑制浓度IC50。
评估结果:这些组合物在可接受的生物浓度下，细胞毒性低。针对对抗冠状病毒SARS-CoV-2的各种药物组合物，也观察到显著和积极的抗病毒活性。这种药物组合物可以被认为是对抗新冠肺炎的候选药物。
Claims (8)
1.一种药物组合物，其特征在于，包含活性成分d-柠檬烯、羽扇豆醇、β-谷甾醇、肉桂醛和姜黄素，表儿茶素以及混合物。
2.根据权利要求1所述的药物组合物，其特征在于，进一步包括所述d-柠檬烯、所述羽扇豆醇、所述β-谷甾醇、所述肉桂醛的混合物；或所述d-柠檬烯、所述羽扇豆醇、所述b-谷甾醇、所述肉桂醛和表没食子儿茶素没食子酸酯(EGCG)的混合物；或所述d-柠檬烯、所述羽扇豆醇、所述β-谷甾醇、所述肉桂醛和姜黄素的混合物；或所述d-柠檬烯、所述羽扇豆醇、所述β-谷甾醇、所述肉桂醛、所述表没食子儿茶素没食子酸酯(EGCG)和所述姜黄素的混合物。
3.根据前述权利要求中任一项所述的药物组合物，其特征在于，作为活性成分总质量的加权百分比，所述药物组合物包含基本上等于或高于10重量百分比，且基本上等于或低于55重量百分比的所述d-柠檬烯，特别地，所述d-柠檬烯基本上等于或高于20重量百分比，且基本上等于或低于40重量百分比；
所述羽扇豆醇的比例基本上等于或高于15%，且基本上等于或低于55%，特别地，所述羽扇豆醇基本上等于或高于30%，且基本上等于或低于40%；
所述β-谷甾醇的比例基本上等于或高于10%，且基本上等于或低于45%，特别地，所述β-谷甾醇基本上等于或高于15%且基本上等于或低于30%；
所述肉桂醛的比例基本上等于或高于15%，且基本上等于或低于45%，特别地， 所述肉桂醛基本上等于或高于20%，且基本上等于或低于40%；
所述表没食子儿茶素没食子酸酯(EGCG)的比例基本上等于或高15%，且基本上等于或低于40%，特别地，所述表没食子儿茶素没食子酸酯(EGCG)基本上等于或高于25%，且基本上等于或低于35%；
所述姜黄素的比例基本上等于或高于15 %，且基本上等于或低于40%，特别地，所述姜黄素基本上等于或高于25 %，且基本上等于或低于35 %。
4.根据前述权利要求中任一项所述的药物组合物，用于由包膜病原体引起的感染的预防性和/或治愈性治疗。
5.根据前述权利要求中任一项所述的药物组合物，用于治疗慢性炎性和/或由碳水化合物失衡和/或脂质失衡和/或细胞胆固醇转运蛋白功能障碍和/或严重急性呼吸综合征和/或全身性免疫过度激活引起的慢性炎症，特别适用于感染了包膜病原体的患者和合并症患者中。
6.根据前述权利要求中任一项所述的药物组合物，其特征在于，所述药物组合物分解并重构了细胞的脂质组成，特别是细胞膜脂筏的脂质组成，改变其中发现的蛋白质的组成，因此防止这些微区的稳定、防止包膜病原体渗透入细胞、阻止许多生理病理过程中涉及的信号传导途径，尤其是在感染、癌症、肥胖症、代谢性疾病、自身免疫性疾病和神经退行性疾病中的信号传导途径。
7.根据前述权利要求中任一项所述的药物组合物，用于治疗由包膜病原体及其变体引起的感染，特别是冠状病毒科(SARS- CoV，MERS-CoV，SARS-CoV-2)，疱疹病毒科(单纯疱疹，水痘带状疱疹，人类疱疹病毒第四型（EBV），人类疱疹病毒6至7型（HHV-6 to 7）、疱疹病毒B)、逆转录病毒(慢病毒属，包括HIV-1病毒和HIV-2病毒、肿瘤病毒和泡沫病毒)、粘病毒、副粘病毒科(副流感病毒、腮腺炎病毒、麻疹病毒、呼吸道合胞病毒)、狂犬病病毒、拉沙病毒、汉坦病毒、马尔堡病毒、风疹病毒)以及用于治疗癌症。
8.一种药物制剂，其特征在于，包含根据前述权利要求中任一项所述的药物组合物，此外，包含混合或单独包装地至少一种抗炎剂、和/或抗糖尿病剂、和/或降血脂剂、和/或抗感染剂、和/或抗癌剂，用于治疗由病原体引起的感染及其并发症。
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR2103144A FR3121038B1 (fr) | 2021-03-27 | 2021-03-27 | Composition pharmaceutique destinée à inhiber l’infectiosité des virus à bicouche lipidique, à traiter les maladies associées et leurs complications. |
| FRFR2103144 | 2021-03-27 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN115120599A true CN115120599A (zh) | 2022-09-30 |
Family
ID=75690587
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202210292412.1A Pending CN115120599A (zh) | 2021-03-27 | 2022-03-24 | 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 |
Country Status (4)
| Country | Link |
|---|---|
| US (1) | US11918591B2 (zh) |
| EP (1) | EP4119134A1 (zh) |
| CN (1) | CN115120599A (zh) |
| FR (1) | FR3121038B1 (zh) |
Citations (2)
| 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 |
| CN111658631A (zh) * | 2020-06-11 | 2020-09-15 | 广东盛普生命科技有限公司 | 没食子酸及其衍生物和结构类似物在制备抗冠状病毒药物方面的应用 |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0826980A (ja) * | 1994-07-14 | 1996-01-30 | Tsumura & Co | 抗ウイルス剤 |
| FR2973249B1 (fr) * | 2011-03-28 | 2014-02-07 | Centre Nat Rech Scient | Utilisation de l'epigallocatechine gallate comme agent antiviral contre les infections par le virus de l'hepatite c |
| 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 |
-
2021
- 2021-03-27 FR FR2103144A patent/FR3121038B1/fr active Active
-
2022
- 2022-03-22 US US17/700,547 patent/US11918591B2/en active Active
- 2022-03-24 CN CN202210292412.1A patent/CN115120599A/zh active Pending
- 2022-03-25 EP EP22315076.4A patent/EP4119134A1/fr active Pending
Patent Citations (3)
| 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 |
| CN110139643A (zh) * | 2017-01-07 | 2019-08-16 | 居伊福斯坦·蒙卡姆尼楚 | 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 |
| CN111658631A (zh) * | 2020-06-11 | 2020-09-15 | 广东盛普生命科技有限公司 | 没食子酸及其衍生物和结构类似物在制备抗冠状病毒药物方面的应用 |
Non-Patent Citations (2)
| Title |
|---|
| SEEMA A.KULKARNI，等: "Computational evaluation of major components from plant essential oils as potent inhibitors of SARS-CoV-2 spike protein", JOURNAL OF MOLECULAR STRUCTURE, vol. 1221, 4 July 2020 (2020-07-04), pages 1, XP086367096, DOI: 10.1016/j.molstruc.2020.128823 * |
| WAEL H. ROSHDY，等: "EGYVIR: An immunomodulatory herbal extract with potent antiviral activity against SARS-CoV-2", PLOS ONE, vol. 15, no. 11, 18 November 2020 (2020-11-18), pages 1 - 2 * |
Also Published As
| Publication number | Publication date |
|---|---|
| US11918591B2 (en) | 2024-03-05 |
| FR3121038A1 (fr) | 2022-09-30 |
| FR3121038B1 (fr) | 2024-06-14 |
| EP4119134A1 (fr) | 2023-01-18 |
| US20220305029A1 (en) | 2022-09-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US10987329B1 (en) | Combination therapy for coronavirus infections including the novel corona virus (COVID-19) | |
| EP2983661B1 (en) | Formulations of oxabicycloheptanes and oxabicycloheptenes | |
| US20200268770A1 (en) | Pharmaceutical composition used for treating metabolic syndrome disorders, infectious diseases, and complications thereof | |
| Istrate et al. | Rotavirus infection increases intestinal motility but not permeability at the onset of diarrhea | |
| EP3552630A1 (en) | Nhe3-binding compounds for inhibiting phosphate transport | |
| CN115120599A (zh) | 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 | |
| US20210060034A1 (en) | The Pharmaceutical Composition Intended to Inhibit HIV Infectivity in Order to Treat the Acquired Immune Deficiency Syndrome (AIDS) and Its Complications | |
| JP3507511B2 (ja) | アルグラビン（ａｒｇｌａｂｉｎ）およびアルグラビン誘導体の薬学的組成物 | |
| US9616041B2 (en) | Methods and compositions for the treatment of diverticulosis | |
| WO2022015198A1 (ru) | Вакцина и способ защиты от коронавирусной инфекции | |
| JP6227535B2 (ja) | 脂質異常症の予防又は治療薬 | |
| KR102235218B1 (ko) | 감마-테르피넨을 포함하는 자궁경부암 예방 또는 치료용 조성물 | |
| KR20220113456A (ko) | 암의 재발을 예방하기 위한 조성물 및 방법 | |
| US20120190886A1 (en) | Composition for lowering blood uric acid level | |
| WO2016070063A1 (en) | Compositions and methods for treating hiv-associated cognitive dysfunction | |
| US20240165148A1 (en) | Hyaluronic acid-conjugated dipalmitoyl phosphatidyl ethanolamine in combination with non-steroidal anti-inflammatory drugs (nsaids) for treating or alleviating inflammatory diseases | |
| KR101648740B1 (ko) | 실로스타졸을 유효성분으로 포함하는 독소루비신에 의한 심부전 또는 확장성 심근병증의 예방용 약학 조성물 | |
| US20230181515A1 (en) | Treatment and prevention of infections using vegetable oil-derived polyols | |
| CN114159427B (zh) | 一种包含安卓幸醇的组合物用于制备抑制肝癌细胞或肝癌干细胞生长的药物的用途 | |
| WO2006085523A1 (ja) | 血糖値上昇抑制用組成物 | |
| WO2021207217A1 (en) | Compositions and methods for treating viruses | |
| Pagare et al. | The antisickling agent, 5‐hydroxymethyl‐2‐furfural: Other potential pharmacological applications | |
| KR20220165520A (ko) | 헵시딘 억제제를 포함하는 노인성 뇌질환의 예방, 개선, 및/또는 치료용 조성물 | |
| WO2022204431A1 (en) | Prevention and treatment of coronavirus infection | |
| US11110146B2 (en) | Methods for reducing platelet aggregation and treating cardiovascular disease and other medical disorders |
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 |