CN102827272B - 一种叶酸偶联抗体药物及其制备方法与应用 - Google Patents
一种叶酸偶联抗体药物及其制备方法与应用 Download PDFInfo
- Publication number
- CN102827272B CN102827272B CN201210299910.5A CN201210299910A CN102827272B CN 102827272 B CN102827272 B CN 102827272B CN 201210299910 A CN201210299910 A CN 201210299910A CN 102827272 B CN102827272 B CN 102827272B
- Authority
- CN
- China
- Prior art keywords
- igg
- gsh
- folate
- folic acid
- conjugate
- 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.)
- Active
Links
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 title claims abstract description 156
- 239000011724 folic acid Substances 0.000 title claims abstract description 127
- 235000019152 folic acid Nutrition 0.000 title claims abstract description 115
- 229940014144 folate Drugs 0.000 title claims abstract description 59
- 238000002360 preparation method Methods 0.000 title claims abstract description 45
- 230000008878 coupling Effects 0.000 title claims abstract description 30
- 238000010168 coupling process Methods 0.000 title claims abstract description 30
- 238000005859 coupling reaction Methods 0.000 title claims abstract description 30
- 229940125644 antibody drug Drugs 0.000 title abstract 4
- 239000003814 drug Substances 0.000 claims abstract description 55
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 40
- 208000023275 Autoimmune disease Diseases 0.000 claims abstract description 27
- 238000011282 treatment Methods 0.000 claims abstract description 22
- 230000002829 reductive effect Effects 0.000 claims abstract description 12
- 238000006243 chemical reaction Methods 0.000 claims description 60
- 230000004913 activation Effects 0.000 claims description 54
- 229960000304 folic acid Drugs 0.000 claims description 46
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 claims description 40
- 239000000047 product Substances 0.000 claims description 34
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 33
- 239000000243 solution Substances 0.000 claims description 31
- 239000002808 molecular sieve Substances 0.000 claims description 23
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 claims description 23
- 229940064302 folacin Drugs 0.000 claims description 22
- 239000007924 injection Substances 0.000 claims description 22
- 238000002347 injection Methods 0.000 claims description 22
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 claims description 21
- 238000000034 method Methods 0.000 claims description 20
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 20
- 230000037396 body weight Effects 0.000 claims description 14
- 210000004881 tumor cell Anatomy 0.000 claims description 14
- JJAHTWIKCUJRDK-UHFFFAOYSA-N succinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate Chemical group C1CC(CN2C(C=CC2=O)=O)CCC1C(=O)ON1C(=O)CCC1=O JJAHTWIKCUJRDK-UHFFFAOYSA-N 0.000 claims description 13
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 claims description 12
- 239000003638 chemical reducing agent Substances 0.000 claims description 12
- 206010025135 lupus erythematosus Diseases 0.000 claims description 12
- 239000000463 material Substances 0.000 claims description 11
- 230000009467 reduction Effects 0.000 claims description 11
- PMJWDPGOWBRILU-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 4-[4-(2,5-dioxopyrrol-1-yl)phenyl]butanoate Chemical compound O=C1CCC(=O)N1OC(=O)CCCC(C=C1)=CC=C1N1C(=O)C=CC1=O PMJWDPGOWBRILU-UHFFFAOYSA-N 0.000 claims description 10
- SGVWDRVQIYUSRA-UHFFFAOYSA-N 1-[2-[2-(2,5-dioxopyrrol-1-yl)ethyldisulfanyl]ethyl]pyrrole-2,5-dione Chemical compound O=C1C=CC(=O)N1CCSSCCN1C(=O)C=CC1=O SGVWDRVQIYUSRA-UHFFFAOYSA-N 0.000 claims description 9
- 206010006187 Breast cancer Diseases 0.000 claims description 9
- 230000002757 inflammatory effect Effects 0.000 claims description 9
- MKNJJMHQBYVHRS-UHFFFAOYSA-M sodium;1-[11-(2,5-dioxopyrrol-1-yl)undecanoyloxy]-2,5-dioxopyrrolidine-3-sulfonate Chemical compound [Na+].O=C1C(S(=O)(=O)[O-])CC(=O)N1OC(=O)CCCCCCCCCCN1C(=O)C=CC1=O MKNJJMHQBYVHRS-UHFFFAOYSA-M 0.000 claims description 9
- 208000026310 Breast neoplasm Diseases 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 8
- 230000001185 psoriatic effect Effects 0.000 claims description 8
- ULARYIUTHAWJMU-UHFFFAOYSA-M sodium;1-[4-(2,5-dioxopyrrol-1-yl)butanoyloxy]-2,5-dioxopyrrolidine-3-sulfonate Chemical compound [Na+].O=C1C(S(=O)(=O)[O-])CC(=O)N1OC(=O)CCCN1C(=O)C=CC1=O ULARYIUTHAWJMU-UHFFFAOYSA-M 0.000 claims description 8
- 125000003368 amide group Chemical group 0.000 claims description 7
- 208000032839 leukemia Diseases 0.000 claims description 7
- 238000002560 therapeutic procedure Methods 0.000 claims description 7
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 claims description 6
- 206010008342 Cervix carcinoma Diseases 0.000 claims description 6
- 206010009944 Colon cancer Diseases 0.000 claims description 6
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 6
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 claims description 6
- 201000010881 cervical cancer Diseases 0.000 claims description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
- 238000010254 subcutaneous injection Methods 0.000 claims description 6
- 239000007929 subcutaneous injection Substances 0.000 claims description 6
- 230000003213 activating effect Effects 0.000 claims description 5
- 239000006227 byproduct Substances 0.000 claims description 5
- 201000010989 colorectal carcinoma Diseases 0.000 claims description 5
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 5
- 210000003462 vein Anatomy 0.000 claims description 5
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 4
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 4
- 206010033128 Ovarian cancer Diseases 0.000 claims description 4
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- 201000005202 lung cancer Diseases 0.000 claims description 4
- 208000020816 lung neoplasm Diseases 0.000 claims description 4
- 210000003205 muscle Anatomy 0.000 claims description 4
- OGMADIBCHLQMIP-UHFFFAOYSA-N 2-aminoethanethiol;hydron;chloride Chemical compound Cl.NCCS OGMADIBCHLQMIP-UHFFFAOYSA-N 0.000 claims description 3
- 206010014759 Endometrial neoplasm Diseases 0.000 claims description 3
- 206010014967 Ependymoma Diseases 0.000 claims description 3
- 229910052786 argon Inorganic materials 0.000 claims description 3
- 201000003914 endometrial carcinoma Diseases 0.000 claims description 3
- 238000001914 filtration Methods 0.000 claims description 3
- 239000007789 gas Substances 0.000 claims description 3
- 201000007270 liver cancer Diseases 0.000 claims description 3
- 208000014018 liver neoplasm Diseases 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 230000008569 process Effects 0.000 claims description 3
- LLXVXPPXELIDGQ-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 3-(2,5-dioxopyrrol-1-yl)benzoate Chemical compound C=1C=CC(N2C(C=CC2=O)=O)=CC=1C(=O)ON1C(=O)CCC1=O LLXVXPPXELIDGQ-UHFFFAOYSA-N 0.000 claims description 2
- LCZVQHWMSQLWSC-UHFFFAOYSA-N 1-[4-(2,5-dioxopyrrol-1-yl)butanoyloxy]-2,5-dioxopyrrolidine-3-sulfonic acid Chemical compound O=C1C(S(=O)(=O)O)CC(=O)N1OC(=O)CCCN1C(=O)C=CC1=O LCZVQHWMSQLWSC-UHFFFAOYSA-N 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 239000007788 liquid Substances 0.000 claims description 2
- 239000000843 powder Substances 0.000 claims description 2
- 208000005069 pulmonary fibrosis Diseases 0.000 claims description 2
- 229910021642 ultra pure water Inorganic materials 0.000 claims description 2
- 239000012498 ultrapure water Substances 0.000 claims description 2
- 125000003929 folic acid group Chemical group 0.000 claims 2
- 201000003651 pulmonary sarcoidosis Diseases 0.000 claims 1
- 238000007873 sieving Methods 0.000 claims 1
- 229960003180 glutathione Drugs 0.000 abstract description 45
- 229940079593 drug Drugs 0.000 abstract description 22
- 201000011510 cancer Diseases 0.000 abstract description 18
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 16
- 201000010099 disease Diseases 0.000 abstract description 15
- 230000003013 cytotoxicity Effects 0.000 abstract description 8
- 231100000135 cytotoxicity Toxicity 0.000 abstract description 8
- 230000008685 targeting Effects 0.000 abstract description 8
- 102000006815 folate receptor Human genes 0.000 abstract description 7
- 108020005243 folate receptor Proteins 0.000 abstract description 7
- 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 abstract description 5
- 230000008512 biological response Effects 0.000 abstract description 3
- 230000004154 complement system Effects 0.000 abstract description 3
- 108010024636 Glutathione Proteins 0.000 abstract description 2
- 230000006378 damage Effects 0.000 abstract description 2
- 125000003277 amino group Chemical group 0.000 abstract 1
- 230000000091 immunopotentiator Effects 0.000 abstract 1
- HUOOMAOYXQFIDQ-UHFFFAOYSA-N isoginkgetin Chemical compound C1=CC(OC)=CC=C1C1=CC(=O)C2=C(O)C=C(O)C(C=3C(=CC=C(C=3)C=3OC4=CC(O)=CC(O)=C4C(=O)C=3)OC)=C2O1 HUOOMAOYXQFIDQ-UHFFFAOYSA-N 0.000 description 178
- 241000699666 Mus <mouse, genus> Species 0.000 description 43
- 210000004027 cell Anatomy 0.000 description 32
- 230000000694 effects Effects 0.000 description 27
- -1 sulfosuccinimide ester Chemical class 0.000 description 17
- 102000005962 receptors Human genes 0.000 description 15
- 108020003175 receptors Proteins 0.000 description 15
- 238000012360 testing method Methods 0.000 description 14
- 241001465754 Metazoa Species 0.000 description 13
- 241000700159 Rattus Species 0.000 description 13
- 210000001072 colon Anatomy 0.000 description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- 239000007928 intraperitoneal injection Substances 0.000 description 11
- 239000000203 mixture Substances 0.000 description 11
- 238000001556 precipitation Methods 0.000 description 11
- 230000003187 abdominal effect Effects 0.000 description 10
- 206010025482 malaise Diseases 0.000 description 10
- 239000000376 reactant Substances 0.000 description 10
- JWDFQMWEFLOOED-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 3-(pyridin-2-yldisulfanyl)propanoate Chemical compound O=C1CCC(=O)N1OC(=O)CCSSC1=CC=CC=N1 JWDFQMWEFLOOED-UHFFFAOYSA-N 0.000 description 9
- 210000002540 macrophage Anatomy 0.000 description 9
- 210000002966 serum Anatomy 0.000 description 9
- 238000011033 desalting Methods 0.000 description 8
- 238000011160 research Methods 0.000 description 8
- VLARLSIGSPVYHX-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 6-(2,5-dioxopyrrol-1-yl)hexanoate Chemical compound O=C1CCC(=O)N1OC(=O)CCCCCN1C(=O)C=CC1=O VLARLSIGSPVYHX-UHFFFAOYSA-N 0.000 description 7
- QYEAAMBIUQLHFQ-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 6-[3-(pyridin-2-yldisulfanyl)propanoylamino]hexanoate Chemical compound O=C1CCC(=O)N1OC(=O)CCCCCNC(=O)CCSSC1=CC=CC=N1 QYEAAMBIUQLHFQ-UHFFFAOYSA-N 0.000 description 7
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 7
- 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 7
- 102000003896 Myeloperoxidases Human genes 0.000 description 7
- 108090000235 Myeloperoxidases Proteins 0.000 description 7
- 239000012190 activator Substances 0.000 description 7
- 230000002583 anti-histone Effects 0.000 description 7
- 239000003153 chemical reaction reagent Substances 0.000 description 7
- 230000007246 mechanism Effects 0.000 description 7
- 229960000485 methotrexate Drugs 0.000 description 7
- 230000004083 survival effect Effects 0.000 description 7
- 210000001519 tissue Anatomy 0.000 description 7
- 238000011765 DBA/2 mouse Methods 0.000 description 6
- 206010060820 Joint injury Diseases 0.000 description 6
- 238000010171 animal model Methods 0.000 description 6
- 238000013016 damping Methods 0.000 description 6
- 238000001514 detection method Methods 0.000 description 6
- 239000012530 fluid Substances 0.000 description 6
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 6
- 239000002504 physiological saline solution Substances 0.000 description 6
- 238000010998 test method Methods 0.000 description 6
- 239000004971 Cross linker Substances 0.000 description 5
- 206010061218 Inflammation Diseases 0.000 description 5
- 210000002683 foot Anatomy 0.000 description 5
- 230000004054 inflammatory process Effects 0.000 description 5
- 230000001404 mediated effect Effects 0.000 description 5
- 239000013641 positive control Substances 0.000 description 5
- 210000003491 skin Anatomy 0.000 description 5
- KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical compound O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 5
- 210000003371 toe Anatomy 0.000 description 5
- WCMOHMXWOOBVMZ-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 6-[3-(2,5-dioxopyrrol-1-yl)propanoylamino]hexanoate Chemical compound O=C1CCC(=O)N1OC(=O)CCCCCNC(=O)CCN1C(=O)C=CC1=O WCMOHMXWOOBVMZ-UHFFFAOYSA-N 0.000 description 4
- VOBDXTSTTMAKHK-VHDCPBDGSA-N 3870-07-3 Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H]3OC(C)(C)O[C@@]3(C(=O)COC(=O)C)[C@@]1(C)C[C@@H]2O VOBDXTSTTMAKHK-VHDCPBDGSA-N 0.000 description 4
- AOJJSUZBOXZQNB-VTZDEGQISA-N 4'-epidoxorubicin 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-VTZDEGQISA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 102000010451 Folate receptor alpha Human genes 0.000 description 4
- 108050001931 Folate receptor alpha Proteins 0.000 description 4
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 4
- 108010002350 Interleukin-2 Proteins 0.000 description 4
- 102000000588 Interleukin-2 Human genes 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 4
- 230000009471 action Effects 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 230000001580 bacterial effect Effects 0.000 description 4
- 244000309466 calf Species 0.000 description 4
- 230000004700 cellular uptake Effects 0.000 description 4
- 239000002674 ointment Substances 0.000 description 4
- 238000011275 oncology therapy Methods 0.000 description 4
- 210000000056 organ Anatomy 0.000 description 4
- 230000007170 pathology Effects 0.000 description 4
- 238000012545 processing Methods 0.000 description 4
- 238000012552 review Methods 0.000 description 4
- 239000000523 sample Substances 0.000 description 4
- 201000000306 sarcoidosis Diseases 0.000 description 4
- JGMJQSFLQWGYMQ-UHFFFAOYSA-M sodium;2,6-dichloro-n-phenylaniline;acetate Chemical compound [Na+].CC([O-])=O.ClC1=CC=CC(Cl)=C1NC1=CC=CC=C1 JGMJQSFLQWGYMQ-UHFFFAOYSA-M 0.000 description 4
- JKHVDAUOODACDU-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 3-(2,5-dioxopyrrol-1-yl)propanoate Chemical compound O=C1CCC(=O)N1OC(=O)CCN1C(=O)C=CC1=O JKHVDAUOODACDU-UHFFFAOYSA-N 0.000 description 3
- PVGATNRYUYNBHO-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 4-(2,5-dioxopyrrol-1-yl)butanoate Chemical compound O=C1CCC(=O)N1OC(=O)CCCN1C(=O)C=CC1=O PVGATNRYUYNBHO-UHFFFAOYSA-N 0.000 description 3
- IHVODYOQUSEYJJ-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 6-[[4-[(2,5-dioxopyrrol-1-yl)methyl]cyclohexanecarbonyl]amino]hexanoate Chemical compound O=C1CCC(=O)N1OC(=O)CCCCCNC(=O)C(CC1)CCC1CN1C(=O)C=CC1=O IHVODYOQUSEYJJ-UHFFFAOYSA-N 0.000 description 3
- ASNTZYQMIUCEBV-UHFFFAOYSA-N 2,5-dioxo-1-[6-[3-(pyridin-2-yldisulfanyl)propanoylamino]hexanoyloxy]pyrrolidine-3-sulfonic acid Chemical group O=C1C(S(=O)(=O)O)CC(=O)N1OC(=O)CCCCCNC(=O)CCSSC1=CC=CC=N1 ASNTZYQMIUCEBV-UHFFFAOYSA-N 0.000 description 3
- 206010009900 Colitis ulcerative Diseases 0.000 description 3
- 102000010449 Folate receptor beta Human genes 0.000 description 3
- 108050001930 Folate receptor beta Proteins 0.000 description 3
- 201000004681 Psoriasis Diseases 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 201000006704 Ulcerative Colitis Diseases 0.000 description 3
- DPDMMXDBJGCCQC-UHFFFAOYSA-N [Na].[Cl] Chemical compound [Na].[Cl] DPDMMXDBJGCCQC-UHFFFAOYSA-N 0.000 description 3
- 239000002671 adjuvant Substances 0.000 description 3
- 239000003470 adrenal cortex hormone Substances 0.000 description 3
- 239000000427 antigen Substances 0.000 description 3
- 102000036639 antigens Human genes 0.000 description 3
- 108091007433 antigens Proteins 0.000 description 3
- 230000006399 behavior Effects 0.000 description 3
- 208000004921 cutaneous lupus erythematosus Diseases 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- 229960001193 diclofenac sodium Drugs 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 3
- 238000011835 investigation Methods 0.000 description 3
- 239000002502 liposome Substances 0.000 description 3
- 230000003211 malignant effect Effects 0.000 description 3
- 230000008506 pathogenesis Effects 0.000 description 3
- 230000035755 proliferation Effects 0.000 description 3
- 230000000452 restraining effect Effects 0.000 description 3
- 230000028327 secretion Effects 0.000 description 3
- 239000001488 sodium phosphate Substances 0.000 description 3
- 229910000162 sodium phosphate Inorganic materials 0.000 description 3
- MIDXXTLMKGZDPV-UHFFFAOYSA-M sodium;1-[6-(2,5-dioxopyrrol-1-yl)hexanoyloxy]-2,5-dioxopyrrolidine-3-sulfonate Chemical compound [Na+].O=C1C(S(=O)(=O)[O-])CC(=O)N1OC(=O)CCCCCN1C(=O)C=CC1=O MIDXXTLMKGZDPV-UHFFFAOYSA-M 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 229960002317 succinimide Drugs 0.000 description 3
- 230000000472 traumatic effect Effects 0.000 description 3
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 3
- TYKASZBHFXBROF-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 2-(2,5-dioxopyrrol-1-yl)acetate Chemical compound O=C1CCC(=O)N1OC(=O)CN1C(=O)C=CC1=O TYKASZBHFXBROF-UHFFFAOYSA-N 0.000 description 2
- LTDQGCFMTVHZKP-UHFFFAOYSA-N (4-bromophenyl)-(4,6-dimethoxy-3-methyl-1-benzofuran-2-yl)methanone Chemical compound O1C2=CC(OC)=CC(OC)=C2C(C)=C1C(=O)C1=CC=C(Br)C=C1 LTDQGCFMTVHZKP-UHFFFAOYSA-N 0.000 description 2
- RVRLFABOQXZUJX-UHFFFAOYSA-N 1-[1-(2,5-dioxopyrrol-1-yl)ethyl]pyrrole-2,5-dione Chemical compound O=C1C=CC(=O)N1C(C)N1C(=O)C=CC1=O RVRLFABOQXZUJX-UHFFFAOYSA-N 0.000 description 2
- AASYSXRGODIQGY-UHFFFAOYSA-N 1-[1-(2,5-dioxopyrrol-1-yl)hexyl]pyrrole-2,5-dione Chemical compound O=C1C=CC(=O)N1C(CCCCC)N1C(=O)C=CC1=O AASYSXRGODIQGY-UHFFFAOYSA-N 0.000 description 2
- FERLGYOHRKHQJP-UHFFFAOYSA-N 1-[2-[2-[2-(2,5-dioxopyrrol-1-yl)ethoxy]ethoxy]ethyl]pyrrole-2,5-dione Chemical group O=C1C=CC(=O)N1CCOCCOCCN1C(=O)C=CC1=O FERLGYOHRKHQJP-UHFFFAOYSA-N 0.000 description 2
- WHEOHCIKAJUSJC-UHFFFAOYSA-N 1-[2-[bis[2-(2,5-dioxopyrrol-1-yl)ethyl]amino]ethyl]pyrrole-2,5-dione Chemical compound O=C1C=CC(=O)N1CCN(CCN1C(C=CC1=O)=O)CCN1C(=O)C=CC1=O WHEOHCIKAJUSJC-UHFFFAOYSA-N 0.000 description 2
- DIYPCWKHSODVAP-UHFFFAOYSA-N 1-[3-(2,5-dioxopyrrol-1-yl)benzoyl]oxy-2,5-dioxopyrrolidine-3-sulfonic acid Chemical compound O=C1C(S(=O)(=O)O)CC(=O)N1OC(=O)C1=CC=CC(N2C(C=CC2=O)=O)=C1 DIYPCWKHSODVAP-UHFFFAOYSA-N 0.000 description 2
- VNJBTKQBKFMEHH-UHFFFAOYSA-N 1-[4-(2,5-dioxopyrrol-1-yl)-2,3-dihydroxybutyl]pyrrole-2,5-dione Chemical compound O=C1C=CC(=O)N1CC(O)C(O)CN1C(=O)C=CC1=O VNJBTKQBKFMEHH-UHFFFAOYSA-N 0.000 description 2
- WXXSHAKLDCERGU-UHFFFAOYSA-N 1-[4-(2,5-dioxopyrrol-1-yl)butyl]pyrrole-2,5-dione Chemical compound O=C1C=CC(=O)N1CCCCN1C(=O)C=CC1=O WXXSHAKLDCERGU-UHFFFAOYSA-N 0.000 description 2
- FPKVOQKZMBDBKP-UHFFFAOYSA-N 1-[4-[(2,5-dioxopyrrol-1-yl)methyl]cyclohexanecarbonyl]oxy-2,5-dioxopyrrolidine-3-sulfonic acid Chemical compound O=C1C(S(=O)(=O)O)CC(=O)N1OC(=O)C1CCC(CN2C(C=CC2=O)=O)CC1 FPKVOQKZMBDBKP-UHFFFAOYSA-N 0.000 description 2
- VYMHBQQZUYHXSS-UHFFFAOYSA-N 2-(3h-dithiol-3-yl)pyridine Chemical compound C1=CSSC1C1=CC=CC=N1 VYMHBQQZUYHXSS-UHFFFAOYSA-N 0.000 description 2
- QGZCUOLOTMJILH-UHFFFAOYSA-N 2h-tetrazol-2-ium;bromide Chemical compound [Br-].C1=N[NH+]=NN1 QGZCUOLOTMJILH-UHFFFAOYSA-N 0.000 description 2
- JMUAKWNHKQBPGJ-UHFFFAOYSA-N 3-(pyridin-2-yldisulfanyl)-n-[4-[3-(pyridin-2-yldisulfanyl)propanoylamino]butyl]propanamide Chemical compound C=1C=CC=NC=1SSCCC(=O)NCCCCNC(=O)CCSSC1=CC=CC=N1 JMUAKWNHKQBPGJ-UHFFFAOYSA-N 0.000 description 2
- ALYNCZNDIQEVRV-UHFFFAOYSA-N 4-aminobenzoic acid Chemical group NC1=CC=C(C(O)=O)C=C1 ALYNCZNDIQEVRV-UHFFFAOYSA-N 0.000 description 2
- 206010002091 Anaesthesia Diseases 0.000 description 2
- 208000008822 Ankylosis Diseases 0.000 description 2
- 0 CCCNC(CCCCCNC(CCSS*C(N*C*)=O)=O)=O Chemical compound CCCNC(CCCCCNC(CCSS*C(N*C*)=O)=O)=O 0.000 description 2
- 206010012434 Dermatitis allergic Diseases 0.000 description 2
- RPNUMPOLZDHAAY-UHFFFAOYSA-N Diethylenetriamine Chemical compound NCCNCCN RPNUMPOLZDHAAY-UHFFFAOYSA-N 0.000 description 2
- 208000006926 Discoid Lupus Erythematosus Diseases 0.000 description 2
- 206010015150 Erythema Diseases 0.000 description 2
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 2
- 241000581650 Ivesia Species 0.000 description 2
- 206010023198 Joint ankylosis Diseases 0.000 description 2
- 238000012449 Kunming mouse Methods 0.000 description 2
- PEEHTFAAVSWFBL-UHFFFAOYSA-N Maleimide Chemical compound O=C1NC(=O)C=C1 PEEHTFAAVSWFBL-UHFFFAOYSA-N 0.000 description 2
- 241001494479 Pecora Species 0.000 description 2
- 239000004698 Polyethylene Substances 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 description 2
- 239000007983 Tris buffer Substances 0.000 description 2
- 208000025865 Ulcer Diseases 0.000 description 2
- 238000012382 advanced drug delivery Methods 0.000 description 2
- CKMXBZGNNVIXHC-UHFFFAOYSA-L ammonium magnesium phosphate hexahydrate Chemical compound [NH4+].O.O.O.O.O.O.[Mg+2].[O-]P([O-])([O-])=O CKMXBZGNNVIXHC-UHFFFAOYSA-L 0.000 description 2
- 230000037005 anaesthesia Effects 0.000 description 2
- 230000000202 analgesic effect Effects 0.000 description 2
- 208000007502 anemia Diseases 0.000 description 2
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- 230000006907 apoptotic process Effects 0.000 description 2
- 230000036528 appetite Effects 0.000 description 2
- 235000019789 appetite Nutrition 0.000 description 2
- CUBCNYWQJHBXIY-UHFFFAOYSA-N benzoic acid;2-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=CC=C1.OC(=O)C1=CC=CC=C1O CUBCNYWQJHBXIY-UHFFFAOYSA-N 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 239000001273 butane Substances 0.000 description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 206010009887 colitis Diseases 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 238000007876 drug discovery Methods 0.000 description 2
- YOMFVLRTMZWACQ-UHFFFAOYSA-N ethyltrimethylammonium Chemical compound CC[N+](C)(C)C YOMFVLRTMZWACQ-UHFFFAOYSA-N 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 108010074605 gamma-Globulins Proteins 0.000 description 2
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 2
- 229910052737 gold Inorganic materials 0.000 description 2
- 239000010931 gold Substances 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 239000012216 imaging agent Substances 0.000 description 2
- 230000028993 immune response Effects 0.000 description 2
- 230000003053 immunization Effects 0.000 description 2
- 238000002649 immunization Methods 0.000 description 2
- 239000003018 immunosuppressive agent Substances 0.000 description 2
- 238000009169 immunotherapy Methods 0.000 description 2
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 210000000936 intestine Anatomy 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 208000002551 irritable bowel syndrome Diseases 0.000 description 2
- 230000002147 killing effect Effects 0.000 description 2
- 230000002045 lasting effect Effects 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 239000003607 modifier Substances 0.000 description 2
- IJDNQMDRQITEOD-UHFFFAOYSA-N n-butane Chemical compound CCCC IJDNQMDRQITEOD-UHFFFAOYSA-N 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N n-pentane Natural products CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 2
- 238000003305 oral gavage Methods 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 229920000573 polyethylene Polymers 0.000 description 2
- 230000002035 prolonged effect Effects 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- 235000018102 proteins Nutrition 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 201000001474 proteinuria Diseases 0.000 description 2
- 239000002516 radical scavenger Substances 0.000 description 2
- 230000006798 recombination Effects 0.000 description 2
- 238000005215 recombination Methods 0.000 description 2
- 210000000664 rectum Anatomy 0.000 description 2
- VUFNRPJNRFOTGK-UHFFFAOYSA-M sodium;1-[4-[(2,5-dioxopyrrol-1-yl)methyl]cyclohexanecarbonyl]oxy-2,5-dioxopyrrolidine-3-sulfonate Chemical compound [Na+].O=C1C(S(=O)(=O)[O-])CC(=O)N1OC(=O)C1CCC(CN2C(C=CC2=O)=O)CC1 VUFNRPJNRFOTGK-UHFFFAOYSA-M 0.000 description 2
- 229910052567 struvite Inorganic materials 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- 206010043554 thrombocytopenia Diseases 0.000 description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- 231100000397 ulcer Toxicity 0.000 description 2
- 210000001835 viscera Anatomy 0.000 description 2
- 238000011179 visual inspection Methods 0.000 description 2
- NAWXUBYGYWOOIX-SFHVURJKSA-N (2s)-2-[[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]amino]-4-methylidenepentanedioic acid Chemical compound C1=CC2=NC(N)=NC(N)=C2C=C1CCC1=CC=C(C(=O)N[C@@H](CC(=C)C(O)=O)C(O)=O)C=C1 NAWXUBYGYWOOIX-SFHVURJKSA-N 0.000 description 1
- MSTNYGQPCMXVAQ-RYUDHWBXSA-N (6S)-5,6,7,8-tetrahydrofolic acid Chemical compound C([C@H]1CNC=2N=C(NC(=O)C=2N1)N)NC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 MSTNYGQPCMXVAQ-RYUDHWBXSA-N 0.000 description 1
- WHTVZRBIWZFKQO-AWEZNQCLSA-N (S)-chloroquine Chemical compound ClC1=CC=C2C(N[C@@H](C)CCCN(CC)CC)=CC=NC2=C1 WHTVZRBIWZFKQO-AWEZNQCLSA-N 0.000 description 1
- VHYRLCJMMJQUBY-UHFFFAOYSA-N 1-[4-[4-(2,5-dioxopyrrol-1-yl)phenyl]butanoyloxy]-2,5-dioxopyrrolidine-3-sulfonic acid Chemical compound O=C1C(S(=O)(=O)O)CC(=O)N1OC(=O)CCCC1=CC=C(N2C(C=CC2=O)=O)C=C1 VHYRLCJMMJQUBY-UHFFFAOYSA-N 0.000 description 1
- 201000010000 Agranulocytosis Diseases 0.000 description 1
- 201000004384 Alopecia Diseases 0.000 description 1
- 206010001928 Amenorrhoea Diseases 0.000 description 1
- 208000006820 Arthralgia Diseases 0.000 description 1
- 206010065553 Bone marrow failure Diseases 0.000 description 1
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
- 241000589876 Campylobacter Species 0.000 description 1
- 208000011231 Crohn disease Diseases 0.000 description 1
- 206010011674 Cutaneous sarcoidosis Diseases 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- VVNCNSJFMMFHPL-VKHMYHEASA-N D-penicillamine Chemical compound CC(C)(S)[C@@H](N)C(O)=O VVNCNSJFMMFHPL-VKHMYHEASA-N 0.000 description 1
- 206010048768 Dermatosis Diseases 0.000 description 1
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
- 206010013183 Dislocation of vertebra Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 208000000461 Esophageal Neoplasms Diseases 0.000 description 1
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 1
- 206010018687 Granulocytopenia Diseases 0.000 description 1
- 206010019851 Hepatotoxicity Diseases 0.000 description 1
- 208000017604 Hodgkin disease Diseases 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 108010002352 Interleukin-1 Proteins 0.000 description 1
- 208000005016 Intestinal Neoplasms Diseases 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical group OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- 206010023799 Large intestinal ulcer Diseases 0.000 description 1
- HLFSDGLLUJUHTE-SNVBAGLBSA-N Levamisole Chemical compound C1([C@H]2CN3CCSC3=N2)=CC=CC=C1 HLFSDGLLUJUHTE-SNVBAGLBSA-N 0.000 description 1
- 208000006802 Lupus erythematosus panniculitis Diseases 0.000 description 1
- 102000003735 Mesothelin Human genes 0.000 description 1
- 108090000015 Mesothelin Proteins 0.000 description 1
- 206010028372 Muscular weakness Diseases 0.000 description 1
- 208000003435 Optic Neuritis Diseases 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 108010019160 Pancreatin Proteins 0.000 description 1
- 206010033733 Papule Diseases 0.000 description 1
- 208000037273 Pathologic Processes Diseases 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 description 1
- 108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 description 1
- 241000669298 Pseudaulacaspis pentagona Species 0.000 description 1
- 206010037888 Rash pustular Diseases 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 206010039361 Sacroiliitis Diseases 0.000 description 1
- 206010070834 Sensitisation Diseases 0.000 description 1
- 206010067868 Skin mass Diseases 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 206010041349 Somnolence Diseases 0.000 description 1
- 244000300264 Spinacia oleracea Species 0.000 description 1
- 235000009337 Spinacia oleracea Nutrition 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- 208000018359 Systemic autoimmune disease Diseases 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 102000003929 Transaminases Human genes 0.000 description 1
- 108090000340 Transaminases Proteins 0.000 description 1
- 229930003270 Vitamin B Natural products 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 210000000683 abdominal cavity Anatomy 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 231100000360 alopecia Toxicity 0.000 description 1
- 229950001537 amatuximab Drugs 0.000 description 1
- 210000003423 ankle Anatomy 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000000702 anti-platelet effect Effects 0.000 description 1
- 230000002682 anti-psoriatic effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 230000030741 antigen processing and presentation Effects 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 210000000436 anus Anatomy 0.000 description 1
- XJHSMFDIQHVMCY-UHFFFAOYSA-K aurothiomalate(2-) Chemical compound [O-]C(=O)CC(S[Au])C([O-])=O XJHSMFDIQHVMCY-UHFFFAOYSA-K 0.000 description 1
- 230000005784 autoimmunity Effects 0.000 description 1
- 229940120638 avastin Drugs 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 210000001772 blood platelet Anatomy 0.000 description 1
- 229910052796 boron Inorganic materials 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- 230000003139 buffering effect Effects 0.000 description 1
- 210000005252 bulbus oculi Anatomy 0.000 description 1
- 239000012830 cancer therapeutic Substances 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 238000010523 cascade reaction Methods 0.000 description 1
- 230000011748 cell maturation Effects 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 230000007541 cellular toxicity Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 229960003677 chloroquine Drugs 0.000 description 1
- WHTVZRBIWZFKQO-UHFFFAOYSA-N chloroquine Natural products ClC1=CC=C2C(NC(C)CCCN(CC)CC)=CC=NC2=C1 WHTVZRBIWZFKQO-UHFFFAOYSA-N 0.000 description 1
- 230000008951 colonic inflammation Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 238000011254 conventional chemotherapy Methods 0.000 description 1
- 239000003431 cross linking reagent Substances 0.000 description 1
- PYRZPBDTPRQYKG-UHFFFAOYSA-N cyclopentene-1-carboxylic acid Chemical compound OC(=O)C1=CCCC1 PYRZPBDTPRQYKG-UHFFFAOYSA-N 0.000 description 1
- UFULAYFCSOUIOV-UHFFFAOYSA-N cysteamine Chemical compound NCCS UFULAYFCSOUIOV-UHFFFAOYSA-N 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000013872 defecation Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 229940124447 delivery agent Drugs 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- OZRNSSUDZOLUSN-LBPRGKRZSA-N dihydrofolic acid Chemical compound N=1C=2C(=O)NC(N)=NC=2NCC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OZRNSSUDZOLUSN-LBPRGKRZSA-N 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 1
- 208000002173 dizziness Diseases 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 238000004043 dyeing Methods 0.000 description 1
- 238000004945 emulsification Methods 0.000 description 1
- 239000002662 enteric coated tablet Substances 0.000 description 1
- 208000037902 enteropathy Diseases 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 210000002615 epidermis Anatomy 0.000 description 1
- 231100000321 erythema Toxicity 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 201000004101 esophageal cancer Diseases 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 1
- 238000011010 flushing procedure Methods 0.000 description 1
- 230000003325 follicular Effects 0.000 description 1
- 239000008098 formaldehyde solution Substances 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 238000001476 gene delivery Methods 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000002008 hemorrhagic effect Effects 0.000 description 1
- 230000007686 hepatotoxicity Effects 0.000 description 1
- 231100000304 hepatotoxicity Toxicity 0.000 description 1
- 229940022353 herceptin Drugs 0.000 description 1
- 238000000265 homogenisation Methods 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 208000026278 immune system disease Diseases 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
- 230000006872 improvement Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 229960000905 indomethacin Drugs 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 208000037903 inflammatory enteropathy Diseases 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 201000002313 intestinal cancer Diseases 0.000 description 1
- 208000028774 intestinal disease Diseases 0.000 description 1
- 230000002601 intratumoral effect Effects 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 210000001630 jejunum Anatomy 0.000 description 1
- 230000000366 juvenile effect Effects 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 201000002364 leukopenia Diseases 0.000 description 1
- 231100001022 leukopenia Toxicity 0.000 description 1
- 229960001614 levamisole Drugs 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 210000002751 lymph Anatomy 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 230000000527 lymphocytic effect Effects 0.000 description 1
- 238000007726 management method Methods 0.000 description 1
- 238000013507 mapping Methods 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- 229960003151 mercaptamine Drugs 0.000 description 1
- 210000000713 mesentery Anatomy 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 238000002625 monoclonal antibody therapy Methods 0.000 description 1
- 230000036473 myasthenia Effects 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 208000001749 optic atrophy Diseases 0.000 description 1
- 238000000879 optical micrograph Methods 0.000 description 1
- 230000000242 pagocytic effect Effects 0.000 description 1
- 230000036407 pain Effects 0.000 description 1
- 229940055695 pancreatin Drugs 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 230000009054 pathological process Effects 0.000 description 1
- 210000002381 plasma Anatomy 0.000 description 1
- 210000004180 plasmocyte Anatomy 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 230000037452 priming Effects 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 208000029561 pustule Diseases 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 229960004641 rituximab Drugs 0.000 description 1
- 239000012488 sample solution Substances 0.000 description 1
- 238000004062 sedimentation Methods 0.000 description 1
- 230000008313 sensitization Effects 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
- LKUULGDICDGFIQ-UHFFFAOYSA-M sodium;1-[3-(2,5-dioxopyrrol-1-yl)benzoyl]oxy-2,5-dioxopyrrolidine-3-sulfonate Chemical compound [Na+].O=C1C(S(=O)(=O)[O-])CC(=O)N1OC(=O)C1=CC=CC(N2C(C=CC2=O)=O)=C1 LKUULGDICDGFIQ-UHFFFAOYSA-M 0.000 description 1
- 201000000498 stomach carcinoma Diseases 0.000 description 1
- 208000003265 stomatitis Diseases 0.000 description 1
- 208000011834 subacute cutaneous lupus erythematosus Diseases 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 210000001258 synovial membrane Anatomy 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 238000002626 targeted therapy Methods 0.000 description 1
- 239000005460 tetrahydrofolate Substances 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 229940126622 therapeutic monoclonal antibody Drugs 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
- 230000009978 visual deterioration Effects 0.000 description 1
- 235000019156 vitamin B Nutrition 0.000 description 1
- 239000011720 vitamin B Substances 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
Images
Landscapes
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
Description
Claims (27)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201210299910.5A CN102827272B (zh) | 2010-11-08 | 2010-11-08 | 一种叶酸偶联抗体药物及其制备方法与应用 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201210299910.5A CN102827272B (zh) | 2010-11-08 | 2010-11-08 | 一种叶酸偶联抗体药物及其制备方法与应用 |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201010534357A Division CN102008732B (zh) | 2010-11-08 | 2010-11-08 | 一种叶酸偶联抗体药物及其制备方法与应用 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN102827272A CN102827272A (zh) | 2012-12-19 |
CN102827272B true CN102827272B (zh) | 2014-04-02 |
Family
ID=47330606
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201210299910.5A Active CN102827272B (zh) | 2010-11-08 | 2010-11-08 | 一种叶酸偶联抗体药物及其制备方法与应用 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN102827272B (zh) |
Families Citing this family (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN111381034A (zh) * | 2020-03-03 | 2020-07-07 | 武汉生之源生物科技股份有限公司 | 一种gpc-3抗体包被磁珠及其制备方法、试剂盒 |
CN111643676B (zh) * | 2020-07-10 | 2023-06-30 | 荣昌生物制药(烟台)股份有限公司 | 一种双特异性二聚体、双特异性二聚体-药物偶联物及其应用 |
CN112305222A (zh) * | 2020-11-05 | 2021-02-02 | 东莞市医本生物科技有限公司 | 一种小多聚体酶-抗体片段及其制备与应用 |
CN116120430A (zh) * | 2023-02-27 | 2023-05-16 | 浙江准策生物技术有限公司 | 一种叶酸完全抗原和抗体及其制备方法和应用 |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1842337A (zh) * | 2003-06-26 | 2006-10-04 | 默克阿泼洛发股份公司 | 稳定的5,10-亚甲基四氢叶酸盐药物组合物 |
-
2010
- 2010-11-08 CN CN201210299910.5A patent/CN102827272B/zh active Active
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1842337A (zh) * | 2003-06-26 | 2006-10-04 | 默克阿泼洛发股份公司 | 稳定的5,10-亚甲基四氢叶酸盐药物组合物 |
Non-Patent Citations (3)
Title |
---|
Medicinal Chemistry》.2010,第18卷(第15期),5528–5534. * |
zhang zw et al.Conjugating folic acid to gold nanoparticles through glutathione for targeting and detecting cancer cells.《Bioorganic & Medicinal Chemistry》.2010,第18卷(第15期),5528–5534. |
zhang zw et al.Conjugating folic acid to gold nanoparticles through glutathione for targeting and detecting cancer cells.《Bioorganic & * |
Also Published As
Publication number | Publication date |
---|---|
CN102827272A (zh) | 2012-12-19 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN102008732B (zh) | 一种叶酸偶联抗体药物及其制备方法与应用 | |
AU2017200413B2 (en) | Methods for identification of sites for IgG conjugation | |
JP2023018157A (ja) | 親水性抗体-薬物コンジュゲート | |
CN109310885A (zh) | NaPi2b靶向抗体-药物缀合物及其使用方法 | |
US20210261505A1 (en) | Linker, Antibody-Drug Conjugate Including Same and Use Thereof | |
CN102827272B (zh) | 一种叶酸偶联抗体药物及其制备方法与应用 | |
KR101790649B1 (ko) | 글리코사미노글리칸 화합물 및 이의 제조 방법과 용도 | |
ES2425004A2 (es) | Composición farmacéutica combinada y su uso para prerarar un medicamento destinado al tratamiento de las enfermedades o condiciones funcionales del tracto gastrointestinal | |
CN101985471B (zh) | 叶酸-IgG偶联物及其制备方法与应用 | |
CN109152846A (zh) | 缀合物和缀合试剂 | |
CN112675311A (zh) | 18/19f标记的psma靶向诊疗一体化小分子药物偶联物、制备方法及其应用 | |
CN110759940B (zh) | 连接子、含连接子的抗体偶联药物及连接子的用途 | |
CN101795712A (zh) | 药用化合物 | |
CN103893168A (zh) | 异虎耳草素作为制备抗肿瘤药物以及抗癌逆转剂方面的应用 | |
CN105294852B (zh) | 聚乙二醇与肿瘤坏死因子α或其类似物的偶联物及其医药用途 | |
JPH02504267A (ja) | 肝遮断薬 | |
CN104744518B (zh) | 金属钌配合物及其制备方法和应用 | |
CN107773762B (zh) | 基于pd-l1抗体偶联化疗药物的adc及其制备方法和应用 | |
TW394777B (en) | Tumor affinity peptide, and radioactive diagnostic and radioactive therapeutic agent containing the peptide | |
CN1128157C (zh) | 力达霉素与单抗活性片段的偶联物 | |
RU2685867C2 (ru) | Гибридные белки и белковые конъюгаты на основе белка теплового шока-70 (БТШ70) и способы их применения (варианты) | |
CA3164257C (en) | New immunostimulators and use thereof in immunotherapy | |
Salem et al. | Dehydroemetine in acute amoebiasis | |
CN110144013A (zh) | 一种抗类风湿性关节炎多肽及其应用 | |
CN117337194A (zh) | 包含与吲哚菁绿缀合的聚乙二醇的组合物及其使用方法 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
ASS | Succession or assignment of patent right |
Owner name: SHANGHAI HANSHENG BIOTECHNOLOGY CO., LTD. Free format text: FORMER OWNER: CHINA LONGEVOVS MEDICINES (HUBEI) CO., LTD. Effective date: 20130520 |
|
C41 | Transfer of patent application or patent right or utility model | ||
COR | Change of bibliographic data |
Free format text: CORRECT: ADDRESS; FROM: 430072 WUHAN, HUBEI PROVINCE TO: PUDONG NEW AREA, SHANGHAI |
|
TA01 | Transfer of patent application right |
Effective date of registration: 20130520 Address after: Room 10, building 588-2, 101 Ming Lu, Shanghai, Pudong New Area Applicant after: SHANGHAI HANSHENG BIOTECHNOLOGY CO.,LTD. Address before: 7-5, 430072, building seven, Kanto science and Technology Industrial Zone, East Lake Development Zone, Wuhan, Hubei, 5198-4 Applicant before: WUHAN HUAYAO BIOPHARMACEUTICAL Co.,Ltd. |
|
C14 | Grant of patent or utility model | ||
GR01 | Patent grant | ||
ASS | Succession or assignment of patent right |
Owner name: ZHEJIANG JIANFENG HANSHENG BIOTECHNOLOGY CO., LTD. Free format text: FORMER OWNER: SHANGHAI HANSHENG BIOTECHNOLOGY CO., LTD. Effective date: 20140902 |
|
C41 | Transfer of patent application or patent right or utility model | ||
COR | Change of bibliographic data |
Free format text: CORRECT: ADDRESS; FROM: 201203 PUDONG NEW AREA, SHANGHAI TO: 321000 JINHUA, ZHEJIANG PROVINCE |
|
TR01 | Transfer of patent right |
Effective date of registration: 20140902 Address after: 321000 Zhejiang Province, Jinhua city Wucheng District No. 58 Decoction line high fan X02 quality inspection office on the first floor of the building Patentee after: Zhejiang Jianfeng Biotechnology Co.,Ltd. Address before: 201203, room 10, building 588-2, 101 Ming Road, Shanghai, Pudong New Area Patentee before: SHANGHAI HANSHENG BIOTECHNOLOGY CO.,LTD. |
|
C41 | Transfer of patent application or patent right or utility model | ||
TR01 | Transfer of patent right |
Effective date of registration: 20160115 Address after: Yuhang green Ting Road District of Hangzhou City, Zhejiang province 311121 No. 1 Building No. 3 Patentee after: ZHEJIANG HAICHANG BIO-TECH CO.,LTD. Address before: 200123, room 10, building 588-2, 101 Ming Road, Shanghai, Pudong New Area Patentee before: SHANGHAI HANSHENG BIOTECHNOLOGY CO.,LTD. Effective date of registration: 20160115 Address after: 200123, room 10, building 588-2, 101 Ming Road, Shanghai, Pudong New Area Patentee after: SHANGHAI HANSHENG BIOTECHNOLOGY CO.,LTD. Address before: 321000 Zhejiang Province, Jinhua city Wucheng District No. 58 Decoction line high fan X02 quality inspection office on the first floor of the building Patentee before: Zhejiang Jianfeng Biotechnology Co.,Ltd. |
|
CP02 | Change in the address of a patent holder |
Address after: 310000 room 1109, building 2, Wanjing Lake Central West area, Xiasha street, Qiantang new area, Hangzhou, Zhejiang Patentee after: ZHEJIANG HAICHANG BIO-TECH CO.,LTD. Address before: 311121 building 3, No.1 luting Road, Yuhang District, Hangzhou City, Zhejiang Province Patentee before: ZHEJIANG HAICHANG BIO-TECH CO.,LTD. |
|
CP02 | Change in the address of a patent holder |