DK2661275T3 - Sammensætninger og fremgangsmåder til indgivelse af bindingsmidlet med høj oxygenaffinitet til tumorer - Google Patents
Sammensætninger og fremgangsmåder til indgivelse af bindingsmidlet med høj oxygenaffinitet til tumorer Download PDFInfo
- Publication number
- DK2661275T3 DK2661275T3 DK12732165.1T DK12732165T DK2661275T3 DK 2661275 T3 DK2661275 T3 DK 2661275T3 DK 12732165 T DK12732165 T DK 12732165T DK 2661275 T3 DK2661275 T3 DK 2661275T3
- Authority
- DK
- Denmark
- Prior art keywords
- oxygen
- various embodiments
- polymersomes
- myoglobin
- affinity agent
- Prior art date
Links
- 239000001301 oxygen Substances 0.000 title claims description 544
- 229910052760 oxygen Inorganic materials 0.000 title claims description 544
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 title claims description 467
- 206010028980 Neoplasm Diseases 0.000 title claims description 248
- 239000000203 mixture Substances 0.000 title claims description 130
- 238000000034 method Methods 0.000 title claims description 67
- 108010062374 Myoglobin Proteins 0.000 claims description 209
- 102000036675 Myoglobin Human genes 0.000 claims description 208
- 239000002105 nanoparticle Substances 0.000 claims description 193
- 239000003795 chemical substances by application Substances 0.000 claims description 151
- 229920000642 polymer Polymers 0.000 claims description 139
- 238000001959 radiotherapy Methods 0.000 claims description 109
- 230000005855 radiation Effects 0.000 claims description 76
- 239000012528 membrane Substances 0.000 claims description 74
- 230000000694 effects Effects 0.000 claims description 49
- 229920002988 biodegradable polymer Polymers 0.000 claims description 31
- 239000004621 biodegradable polymer Substances 0.000 claims description 31
- 238000002512 chemotherapy Methods 0.000 claims description 22
- 241000894007 species Species 0.000 claims description 22
- 230000001965 increasing effect Effects 0.000 claims description 20
- 239000000126 substance Substances 0.000 claims description 18
- 239000011230 binding agent Substances 0.000 claims description 17
- 239000002534 radiation-sensitizing agent Substances 0.000 claims description 15
- 101000635854 Homo sapiens Myoglobin Proteins 0.000 claims description 13
- 230000036961 partial effect Effects 0.000 claims description 13
- 241000282412 Homo Species 0.000 claims description 11
- 239000002246 antineoplastic agent Substances 0.000 claims description 11
- 230000004087 circulation Effects 0.000 claims description 8
- 229920001059 synthetic polymer Polymers 0.000 claims description 8
- 229940127089 cytotoxic agent Drugs 0.000 claims description 4
- 210000000664 rectum Anatomy 0.000 claims description 4
- 210000001215 vagina Anatomy 0.000 claims description 4
- 239000007788 liquid Substances 0.000 claims description 3
- 229920000575 polymersome Polymers 0.000 description 350
- 239000000969 carrier Substances 0.000 description 147
- 206010021143 Hypoxia Diseases 0.000 description 105
- -1 Poly(Epsilon-Caprolactone) Polymers 0.000 description 101
- 239000003981 vehicle Substances 0.000 description 81
- 239000006185 dispersion Substances 0.000 description 72
- 210000004379 membrane Anatomy 0.000 description 71
- 108010054147 Hemoglobins Proteins 0.000 description 69
- 102000001554 Hemoglobins Human genes 0.000 description 69
- 201000011510 cancer Diseases 0.000 description 69
- 239000008194 pharmaceutical composition Substances 0.000 description 60
- 239000000243 solution Substances 0.000 description 59
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 56
- 238000011068 loading method Methods 0.000 description 55
- 230000007954 hypoxia Effects 0.000 description 47
- 230000027455 binding Effects 0.000 description 46
- 238000011282 treatment Methods 0.000 description 45
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 44
- 229920001577 copolymer Polymers 0.000 description 42
- 238000011160 research Methods 0.000 description 41
- 230000015556 catabolic process Effects 0.000 description 39
- 238000001727 in vivo Methods 0.000 description 39
- 238000006731 degradation reaction Methods 0.000 description 38
- 230000001146 hypoxic effect Effects 0.000 description 37
- 238000006213 oxygenation reaction Methods 0.000 description 35
- 210000004027 cell Anatomy 0.000 description 32
- 238000009472 formulation Methods 0.000 description 31
- 210000004369 blood Anatomy 0.000 description 30
- 239000008280 blood Substances 0.000 description 30
- 238000005538 encapsulation Methods 0.000 description 29
- 239000002245 particle Substances 0.000 description 29
- 239000012071 phase Substances 0.000 description 29
- 210000001519 tissue Anatomy 0.000 description 29
- 229920001610 polycaprolactone Polymers 0.000 description 28
- 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 26
- 238000005259 measurement Methods 0.000 description 25
- 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 24
- 230000008859 change Effects 0.000 description 23
- 239000003446 ligand Substances 0.000 description 23
- 229920000359 diblock copolymer Polymers 0.000 description 22
- 229940079593 drug Drugs 0.000 description 22
- 239000003814 drug Substances 0.000 description 22
- 150000002632 lipids Chemical class 0.000 description 22
- 230000009089 cytolysis Effects 0.000 description 21
- 230000003413 degradative effect Effects 0.000 description 21
- UBAZGMLMVVQSCD-UHFFFAOYSA-N carbon dioxide;molecular oxygen Chemical compound O=O.O=C=O UBAZGMLMVVQSCD-UHFFFAOYSA-N 0.000 description 19
- 150000001875 compounds Chemical class 0.000 description 19
- 230000015572 biosynthetic process Effects 0.000 description 18
- QVMPZNRFXAKISM-UHFFFAOYSA-N tirapazamine Chemical compound C1=CC=C2[N+]([O-])=NC(=N)N(O)C2=C1 QVMPZNRFXAKISM-UHFFFAOYSA-N 0.000 description 18
- 229950002376 tirapazamine Drugs 0.000 description 18
- 238000010494 dissociation reaction Methods 0.000 description 17
- 230000005593 dissociations Effects 0.000 description 17
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 16
- 239000007864 aqueous solution Substances 0.000 description 16
- 229960004316 cisplatin Drugs 0.000 description 16
- 108090000623 proteins and genes Proteins 0.000 description 16
- 102000004169 proteins and genes Human genes 0.000 description 16
- 230000004044 response Effects 0.000 description 16
- 230000008685 targeting Effects 0.000 description 16
- 102000016878 Hypoxia-Inducible Factor 1 Human genes 0.000 description 15
- 108010028501 Hypoxia-Inducible Factor 1 Proteins 0.000 description 15
- 238000009826 distribution Methods 0.000 description 15
- 239000000463 material Substances 0.000 description 15
- 239000000693 micelle Substances 0.000 description 15
- 235000018102 proteins Nutrition 0.000 description 15
- 241001465754 Metazoa Species 0.000 description 14
- 102100034256 Mucin-1 Human genes 0.000 description 14
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 14
- 208000014829 head and neck neoplasm Diseases 0.000 description 14
- 239000002502 liposome Substances 0.000 description 14
- 238000002047 photoemission electron microscopy Methods 0.000 description 14
- 229920001483 poly(ethyl methacrylate) polymer Polymers 0.000 description 14
- 238000002360 preparation method Methods 0.000 description 14
- 239000007787 solid Substances 0.000 description 14
- 239000000725 suspension Substances 0.000 description 14
- 210000004881 tumor cell Anatomy 0.000 description 14
- 230000017531 blood circulation Effects 0.000 description 13
- 238000009792 diffusion process Methods 0.000 description 13
- 230000036571 hydration Effects 0.000 description 13
- 238000006703 hydration reaction Methods 0.000 description 13
- 230000002209 hydrophobic effect Effects 0.000 description 13
- 238000003384 imaging method Methods 0.000 description 13
- 229960004857 mitomycin Drugs 0.000 description 13
- 230000021615 conjugation Effects 0.000 description 12
- 229960004679 doxorubicin Drugs 0.000 description 12
- 238000001125 extrusion Methods 0.000 description 12
- 239000012669 liquid formulation Substances 0.000 description 12
- 201000010881 cervical cancer Diseases 0.000 description 11
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 11
- 238000012377 drug delivery Methods 0.000 description 11
- 239000010408 film Substances 0.000 description 11
- 201000010536 head and neck cancer Diseases 0.000 description 11
- 238000002347 injection Methods 0.000 description 11
- 239000007924 injection Substances 0.000 description 11
- 239000002953 phosphate buffered saline Substances 0.000 description 11
- 238000001338 self-assembly Methods 0.000 description 11
- 230000004083 survival effect Effects 0.000 description 11
- 230000032258 transport Effects 0.000 description 11
- 229920001400 block copolymer Polymers 0.000 description 10
- 230000001413 cellular effect Effects 0.000 description 10
- OBBCSXFCDPPXOL-UHFFFAOYSA-N misonidazole Chemical compound COCC(O)CN1C=CN=C1[N+]([O-])=O OBBCSXFCDPPXOL-UHFFFAOYSA-N 0.000 description 10
- 229950010514 misonidazole Drugs 0.000 description 10
- 239000010409 thin film Substances 0.000 description 10
- 230000035508 accumulation Effects 0.000 description 9
- 238000009825 accumulation Methods 0.000 description 9
- 238000012512 characterization method Methods 0.000 description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 9
- 238000011156 evaluation Methods 0.000 description 9
- 239000011521 glass Substances 0.000 description 9
- 238000000338 in vitro Methods 0.000 description 9
- 230000002601 intratumoral effect Effects 0.000 description 9
- 230000003287 optical effect Effects 0.000 description 9
- 229920001343 polytetrafluoroethylene Polymers 0.000 description 9
- 239000004810 polytetrafluoroethylene Substances 0.000 description 9
- 108090000765 processed proteins & peptides Proteins 0.000 description 9
- 150000003254 radicals Chemical class 0.000 description 9
- 206010020843 Hyperthermia Diseases 0.000 description 8
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 8
- 208000007502 anemia Diseases 0.000 description 8
- 230000033115 angiogenesis Effects 0.000 description 8
- 208000019065 cervical carcinoma Diseases 0.000 description 8
- 238000002296 dynamic light scattering Methods 0.000 description 8
- 238000005516 engineering process Methods 0.000 description 8
- 230000036031 hyperthermia Effects 0.000 description 8
- 230000001404 mediated effect Effects 0.000 description 8
- 229960003966 nicotinamide Drugs 0.000 description 8
- 235000005152 nicotinamide Nutrition 0.000 description 8
- 239000011570 nicotinamide Substances 0.000 description 8
- 229960003753 nitric oxide Drugs 0.000 description 8
- 102000028703 oxygen binding proteins Human genes 0.000 description 8
- 108091009355 oxygen binding proteins Proteins 0.000 description 8
- 230000035699 permeability Effects 0.000 description 8
- 239000008363 phosphate buffer Substances 0.000 description 8
- 229920003023 plastic Polymers 0.000 description 8
- 239000004033 plastic Substances 0.000 description 8
- 229920000747 poly(lactic acid) Polymers 0.000 description 8
- 229920001606 poly(lactic acid-co-glycolic acid) Polymers 0.000 description 8
- 229920005597 polymer membrane Polymers 0.000 description 8
- 238000003860 storage Methods 0.000 description 8
- 230000001225 therapeutic effect Effects 0.000 description 8
- 230000001988 toxicity Effects 0.000 description 8
- 231100000419 toxicity Toxicity 0.000 description 8
- XOHUEYCVLUUEJJ-UHFFFAOYSA-I 2,3-Diphosphoglycerate Chemical group [O-]P(=O)([O-])OC(C(=O)[O-])COP([O-])([O-])=O XOHUEYCVLUUEJJ-UHFFFAOYSA-I 0.000 description 7
- 206010008342 Cervix carcinoma Diseases 0.000 description 7
- 229930012538 Paclitaxel Natural products 0.000 description 7
- 208000000102 Squamous Cell Carcinoma of Head and Neck Diseases 0.000 description 7
- 210000004204 blood vessel Anatomy 0.000 description 7
- 238000007385 chemical modification Methods 0.000 description 7
- 239000000306 component Substances 0.000 description 7
- 230000001976 improved effect Effects 0.000 description 7
- 239000003999 initiator Substances 0.000 description 7
- 238000011835 investigation Methods 0.000 description 7
- 210000004072 lung Anatomy 0.000 description 7
- 238000004519 manufacturing process Methods 0.000 description 7
- 230000007246 mechanism Effects 0.000 description 7
- 229960001592 paclitaxel Drugs 0.000 description 7
- 229920001223 polyethylene glycol Polymers 0.000 description 7
- 230000003389 potentiating effect Effects 0.000 description 7
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 7
- 230000000287 tissue oxygenation Effects 0.000 description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- 229920006362 Teflon® Polymers 0.000 description 6
- 239000013543 active substance Substances 0.000 description 6
- 239000012637 allosteric effector Substances 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 6
- 230000000259 anti-tumor effect Effects 0.000 description 6
- 229920000249 biocompatible polymer Polymers 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 231100000599 cytotoxic agent Toxicity 0.000 description 6
- 239000002619 cytotoxin Substances 0.000 description 6
- 210000003743 erythrocyte Anatomy 0.000 description 6
- 230000006870 function Effects 0.000 description 6
- 201000000459 head and neck squamous cell carcinoma Diseases 0.000 description 6
- 229920001519 homopolymer Polymers 0.000 description 6
- 230000005865 ionizing radiation Effects 0.000 description 6
- 229920002521 macromolecule Polymers 0.000 description 6
- 230000035479 physiological effects, processes and functions Effects 0.000 description 6
- 229920000515 polycarbonate Polymers 0.000 description 6
- 239000004417 polycarbonate Substances 0.000 description 6
- OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 description 6
- 238000012552 review Methods 0.000 description 6
- 230000035945 sensitivity Effects 0.000 description 6
- 238000002560 therapeutic procedure Methods 0.000 description 6
- 230000004614 tumor growth Effects 0.000 description 6
- 201000009030 Carcinoma Diseases 0.000 description 5
- 101710112752 Cytotoxin Proteins 0.000 description 5
- 102000003951 Erythropoietin Human genes 0.000 description 5
- 108090000394 Erythropoietin Proteins 0.000 description 5
- 241000700159 Rattus Species 0.000 description 5
- 229940041181 antineoplastic drug Drugs 0.000 description 5
- 210000003679 cervix uteri Anatomy 0.000 description 5
- 238000000701 chemical imaging Methods 0.000 description 5
- 238000000604 cryogenic transmission electron microscopy Methods 0.000 description 5
- 238000013461 design Methods 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 229940105423 erythropoietin Drugs 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 238000005194 fractionation Methods 0.000 description 5
- 239000012510 hollow fiber Substances 0.000 description 5
- PSGAAPLEWMOORI-PEINSRQWSA-N medroxyprogesterone acetate Chemical compound C([C@@]12C)CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2CC[C@]2(C)[C@@](OC(C)=O)(C(C)=O)CC[C@H]21 PSGAAPLEWMOORI-PEINSRQWSA-N 0.000 description 5
- 238000002156 mixing Methods 0.000 description 5
- 239000000178 monomer Substances 0.000 description 5
- 238000012634 optical imaging Methods 0.000 description 5
- 229920001184 polypeptide Polymers 0.000 description 5
- 229920000166 polytrimethylene carbonate Polymers 0.000 description 5
- 150000004032 porphyrins Chemical class 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- 239000003642 reactive oxygen metabolite Substances 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 238000000527 sonication Methods 0.000 description 5
- 238000001356 surgical procedure Methods 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 4
- LWTUZIMLIKOKDI-UHFFFAOYSA-N 7-chloro-n-[3-(2-nitroimidazol-1-yl)propyl]quinolin-4-amine;hydrochloride Chemical compound Cl.[O-][N+](=O)C1=NC=CN1CCCNC1=CC=NC2=CC(Cl)=CC=C12 LWTUZIMLIKOKDI-UHFFFAOYSA-N 0.000 description 4
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 4
- 102000008015 Hemeproteins Human genes 0.000 description 4
- 108010089792 Hemeproteins Proteins 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 206010027476 Metastases Diseases 0.000 description 4
- 206010070834 Sensitisation Diseases 0.000 description 4
- 206010066901 Treatment failure Diseases 0.000 description 4
- 230000004913 activation Effects 0.000 description 4
- 230000001154 acute effect Effects 0.000 description 4
- 229940100198 alkylating agent Drugs 0.000 description 4
- 239000002168 alkylating agent Substances 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 230000003190 augmentative effect Effects 0.000 description 4
- 239000003633 blood substitute Substances 0.000 description 4
- 208000025188 carcinoma of pharynx Diseases 0.000 description 4
- 239000000084 colloidal system Substances 0.000 description 4
- 239000002131 composite material Substances 0.000 description 4
- 230000001276 controlling effect Effects 0.000 description 4
- 238000007796 conventional method Methods 0.000 description 4
- 238000004132 cross linking Methods 0.000 description 4
- 230000001351 cycling effect Effects 0.000 description 4
- 230000006378 damage Effects 0.000 description 4
- 230000003247 decreasing effect Effects 0.000 description 4
- 230000036425 denaturation Effects 0.000 description 4
- 238000004925 denaturation Methods 0.000 description 4
- 210000004443 dendritic cell Anatomy 0.000 description 4
- 230000001419 dependent effect Effects 0.000 description 4
- OGQYPPBGSLZBEG-UHFFFAOYSA-N dimethyl(dioctadecyl)azanium Chemical compound CCCCCCCCCCCCCCCCCC[N+](C)(C)CCCCCCCCCCCCCCCCCC OGQYPPBGSLZBEG-UHFFFAOYSA-N 0.000 description 4
- 208000035475 disorder Diseases 0.000 description 4
- 239000000839 emulsion Substances 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- WCDWBPCFGJXFJZ-UHFFFAOYSA-N etanidazole Chemical compound OCCNC(=O)CN1C=CN=C1[N+]([O-])=O WCDWBPCFGJXFJZ-UHFFFAOYSA-N 0.000 description 4
- 229960002949 fluorouracil Drugs 0.000 description 4
- 238000004108 freeze drying Methods 0.000 description 4
- 201000003911 head and neck carcinoma Diseases 0.000 description 4
- 230000007062 hydrolysis Effects 0.000 description 4
- 238000006460 hydrolysis reaction Methods 0.000 description 4
- 238000011065 in-situ storage Methods 0.000 description 4
- 210000000867 larynx Anatomy 0.000 description 4
- 208000020816 lung neoplasm Diseases 0.000 description 4
- 230000014759 maintenance of location Effects 0.000 description 4
- 230000003211 malignant effect Effects 0.000 description 4
- 230000009401 metastasis Effects 0.000 description 4
- AARXZCZYLAFQQU-UHFFFAOYSA-N motexafin gadolinium Chemical compound [Gd].CC(O)=O.CC(O)=O.C1=C([N-]2)C(CC)=C(CC)C2=CC(C(=C2C)CCCO)=NC2=CN=C2C=C(OCCOCCOCCOC)C(OCCOCCOCCOC)=CC2=NC=C2C(C)=C(CCCO)C1=N2 AARXZCZYLAFQQU-UHFFFAOYSA-N 0.000 description 4
- 229920006030 multiblock copolymer Polymers 0.000 description 4
- 210000003205 muscle Anatomy 0.000 description 4
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 4
- 230000002265 prevention Effects 0.000 description 4
- 102000004196 processed proteins & peptides Human genes 0.000 description 4
- 238000004393 prognosis Methods 0.000 description 4
- 230000008313 sensitization Effects 0.000 description 4
- 238000004611 spectroscopical analysis Methods 0.000 description 4
- 230000006641 stabilisation Effects 0.000 description 4
- 238000011105 stabilization Methods 0.000 description 4
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 4
- 230000002792 vascular Effects 0.000 description 4
- 206010005003 Bladder cancer Diseases 0.000 description 3
- 206010015866 Extravasation Diseases 0.000 description 3
- 108010085682 Hemoglobin A Proteins 0.000 description 3
- 102000007513 Hemoglobin A Human genes 0.000 description 3
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- HRHKSTOGXBBQCB-UHFFFAOYSA-N Mitomycin E Natural products O=C1C(N)=C(C)C(=O)C2=C1C(COC(N)=O)C1(OC)C3N(C)C3CN12 HRHKSTOGXBBQCB-UHFFFAOYSA-N 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 208000027418 Wounds and injury Diseases 0.000 description 3
- DFPAKSUCGFBDDF-ZQBYOMGUSA-N [14c]-nicotinamide Chemical compound N[14C](=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-ZQBYOMGUSA-N 0.000 description 3
- 229920003232 aliphatic polyester Polymers 0.000 description 3
- 239000004037 angiogenesis inhibitor Substances 0.000 description 3
- 229940121369 angiogenesis inhibitor Drugs 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- 230000006399 behavior Effects 0.000 description 3
- 238000005452 bending Methods 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 239000012620 biological material Substances 0.000 description 3
- 201000008275 breast carcinoma Diseases 0.000 description 3
- 201000006612 cervical squamous cell carcinoma Diseases 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 230000003111 delayed effect Effects 0.000 description 3
- 230000008021 deposition Effects 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- 238000000502 dialysis Methods 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
- 230000036251 extravasation Effects 0.000 description 3
- 150000003278 haem Chemical class 0.000 description 3
- 230000036541 health Effects 0.000 description 3
- 238000010348 incorporation Methods 0.000 description 3
- 230000003993 interaction Effects 0.000 description 3
- 230000003834 intracellular effect Effects 0.000 description 3
- 238000007917 intracranial administration Methods 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 201000005202 lung cancer Diseases 0.000 description 3
- 230000036210 malignancy Effects 0.000 description 3
- 238000007726 management method Methods 0.000 description 3
- HRHKSTOGXBBQCB-VFWICMBZSA-N methylmitomycin Chemical compound O=C1C(N)=C(C)C(=O)C2=C1[C@@H](COC(N)=O)[C@@]1(OC)[C@H]3N(C)[C@H]3CN12 HRHKSTOGXBBQCB-VFWICMBZSA-N 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 230000007935 neutral effect Effects 0.000 description 3
- 150000004957 nitroimidazoles Chemical class 0.000 description 3
- 102000039446 nucleic acids Human genes 0.000 description 3
- 108020004707 nucleic acids Proteins 0.000 description 3
- 150000007523 nucleic acids Chemical class 0.000 description 3
- 238000011275 oncology therapy Methods 0.000 description 3
- 238000005457 optimization Methods 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 230000008520 organization Effects 0.000 description 3
- 239000012466 permeate Substances 0.000 description 3
- 230000004962 physiological condition Effects 0.000 description 3
- 210000002381 plasma Anatomy 0.000 description 3
- 230000004983 pleiotropic effect Effects 0.000 description 3
- 229940065514 poly(lactide) Drugs 0.000 description 3
- 229950004406 porfiromycin Drugs 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 238000011127 radiochemotherapy Methods 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 150000003384 small molecules Chemical class 0.000 description 3
- 230000003595 spectral effect Effects 0.000 description 3
- 238000001228 spectrum Methods 0.000 description 3
- 238000007920 subcutaneous administration Methods 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 230000009885 systemic effect Effects 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 231100000588 tumorigenic Toxicity 0.000 description 3
- 230000000381 tumorigenic effect Effects 0.000 description 3
- 210000005166 vasculature Anatomy 0.000 description 3
- 238000012800 visualization Methods 0.000 description 3
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
- IAKHMKGGTNLKSZ-INIZCTEOSA-N (S)-colchicine Chemical compound C1([C@@H](NC(C)=O)CC2)=CC(=O)C(OC)=CC=C1C1=C2C=C(OC)C(OC)=C1OC IAKHMKGGTNLKSZ-INIZCTEOSA-N 0.000 description 2
- GTLQQCMKADHZLK-UHFFFAOYSA-N 1-oxido-1,2,4-benzotriazin-4-ium 4-oxide Chemical class C1=CC=C2N([O-])N=C[N+](=O)C2=C1 GTLQQCMKADHZLK-UHFFFAOYSA-N 0.000 description 2
- KWVGIHKZDCUPEU-UHFFFAOYSA-N 2,2-dimethoxy-2-phenylacetophenone Chemical compound C=1C=CC=CC=1C(OC)(OC)C(=O)C1=CC=CC=C1 KWVGIHKZDCUPEU-UHFFFAOYSA-N 0.000 description 2
- YZBAXVICWUUHGG-UHFFFAOYSA-N 2-[[4-[2-[dimethyl(oxido)azaniumyl]ethylamino]-5,8-dihydroxy-9,10-dioxoanthracen-1-yl]amino]-n,n-dimethylethanamine oxide Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCC[N+](C)(C)[O-])=CC=C2NCC[N+](C)([O-])C YZBAXVICWUUHGG-UHFFFAOYSA-N 0.000 description 2
- WOVKYSAHUYNSMH-RRKCRQDMSA-N 5-bromodeoxyuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(Br)=C1 WOVKYSAHUYNSMH-RRKCRQDMSA-N 0.000 description 2
- JZQAIMCHSQGJLZ-UHFFFAOYSA-N 5-fluoro-1-(2-oxopropyl)pyrimidine-2,4-dione Chemical compound CC(=O)CN1C=C(F)C(=O)NC1=O JZQAIMCHSQGJLZ-UHFFFAOYSA-N 0.000 description 2
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- 239000000592 Artificial Cell Substances 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- WOVKYSAHUYNSMH-UHFFFAOYSA-N BROMODEOXYURIDINE Natural products C1C(O)C(CO)OC1N1C(=O)NC(=O)C(Br)=C1 WOVKYSAHUYNSMH-UHFFFAOYSA-N 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 2
- 206010006187 Breast cancer Diseases 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 2
- 230000005971 DNA damage repair Effects 0.000 description 2
- 102000012199 E3 ubiquitin-protein ligase Mdm2 Human genes 0.000 description 2
- 108050002772 E3 ubiquitin-protein ligase Mdm2 Proteins 0.000 description 2
- 108010074604 Epoetin Alfa Proteins 0.000 description 2
- 201000008808 Fibrosarcoma Diseases 0.000 description 2
- 208000032612 Glial tumor Diseases 0.000 description 2
- 201000010915 Glioblastoma multiforme Diseases 0.000 description 2
- 206010018338 Glioma Diseases 0.000 description 2
- 108010030158 HBOC 201 Proteins 0.000 description 2
- YZCKVEUIGOORGS-UHFFFAOYSA-N Hydrogen atom Chemical compound [H] YZCKVEUIGOORGS-UHFFFAOYSA-N 0.000 description 2
- 206010020772 Hypertension Diseases 0.000 description 2
- 206010020802 Hypertensive crisis Diseases 0.000 description 2
- 206010023825 Laryngeal cancer Diseases 0.000 description 2
- 102000004895 Lipoproteins Human genes 0.000 description 2
- 108090001030 Lipoproteins Proteins 0.000 description 2
- 208000007433 Lymphatic Metastasis Diseases 0.000 description 2
- 206010025323 Lymphomas Diseases 0.000 description 2
- 229930192392 Mitomycin Natural products 0.000 description 2
- 206010061309 Neoplasm progression Diseases 0.000 description 2
- 206010029155 Nephropathy toxic Diseases 0.000 description 2
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 229920000954 Polyglycolide Polymers 0.000 description 2
- 206010039020 Rhabdomyolysis Diseases 0.000 description 2
- 108020004459 Small interfering RNA Proteins 0.000 description 2
- 229920002125 Sokalan® Polymers 0.000 description 2
- 229920001872 Spider silk Polymers 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 238000003917 TEM image Methods 0.000 description 2
- 239000004809 Teflon Substances 0.000 description 2
- 229920004890 Triton X-100 Polymers 0.000 description 2
- 206010047139 Vasoconstriction Diseases 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- 206010052428 Wound Diseases 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 238000005903 acid hydrolysis reaction Methods 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- RJURFGZVJUQBHK-UHFFFAOYSA-N actinomycin D Natural products CC1OC(=O)C(C(C)C)N(C)C(=O)CN(C)C(=O)C2CCCN2C(=O)C(C(C)C)NC(=O)C1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)NC4C(=O)NC(C(N5CCCC5C(=O)N(C)CC(=O)N(C)C(C(C)C)C(=O)OC4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-UHFFFAOYSA-N 0.000 description 2
- 230000023445 activated T cell autonomous cell death Effects 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 238000011226 adjuvant chemotherapy Methods 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 2
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 2
- 235000011130 ammonium sulphate Nutrition 0.000 description 2
- 229920000469 amphiphilic block copolymer Polymers 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 230000003078 antioxidant effect Effects 0.000 description 2
- 230000001640 apoptogenic effect Effects 0.000 description 2
- 230000006907 apoptotic process Effects 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 238000000149 argon plasma sintering Methods 0.000 description 2
- VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 201000001531 bladder carcinoma Diseases 0.000 description 2
- 230000036772 blood pressure Effects 0.000 description 2
- 238000002725 brachytherapy Methods 0.000 description 2
- 201000008274 breast adenocarcinoma Diseases 0.000 description 2
- 229950004398 broxuridine Drugs 0.000 description 2
- 238000004364 calculation method Methods 0.000 description 2
- 239000012830 cancer therapeutic Substances 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 230000004700 cellular uptake Effects 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- 230000000973 chemotherapeutic effect Effects 0.000 description 2
- ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 230000001086 cytosolic effect Effects 0.000 description 2
- 231100000433 cytotoxic Toxicity 0.000 description 2
- 230000001472 cytotoxic effect Effects 0.000 description 2
- 231100000135 cytotoxicity Toxicity 0.000 description 2
- 230000003013 cytotoxicity Effects 0.000 description 2
- 239000000412 dendrimer Substances 0.000 description 2
- 229920000736 dendritic polymer Polymers 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- DOBMPNYZJYQDGZ-UHFFFAOYSA-N dicoumarol Chemical compound C1=CC=CC2=C1OC(=O)C(CC=1C(OC3=CC=CC=C3C=1O)=O)=C2O DOBMPNYZJYQDGZ-UHFFFAOYSA-N 0.000 description 2
- 229960001912 dicoumarol Drugs 0.000 description 2
- 230000004069 differentiation Effects 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 230000003292 diminished effect Effects 0.000 description 2
- 230000009189 diving Effects 0.000 description 2
- 230000003828 downregulation Effects 0.000 description 2
- 238000009510 drug design Methods 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 210000003038 endothelium Anatomy 0.000 description 2
- 229960003388 epoetin alfa Drugs 0.000 description 2
- QXRSDHAAWVKZLJ-PVYNADRNSA-N epothilone B Chemical compound C/C([C@@H]1C[C@@H]2O[C@]2(C)CCC[C@@H]([C@@H]([C@@H](C)C(=O)C(C)(C)[C@@H](O)CC(=O)O1)O)C)=C\C1=CSC(C)=N1 QXRSDHAAWVKZLJ-PVYNADRNSA-N 0.000 description 2
- 229950006566 etanidazole Drugs 0.000 description 2
- 230000005281 excited state Effects 0.000 description 2
- 238000001249 flow field-flow fractionation Methods 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 238000000799 fluorescence microscopy Methods 0.000 description 2
- 238000001506 fluorescence spectroscopy Methods 0.000 description 2
- 150000002238 fumaric acids Chemical class 0.000 description 2
- 230000004927 fusion Effects 0.000 description 2
- 238000001476 gene delivery Methods 0.000 description 2
- 208000005017 glioblastoma Diseases 0.000 description 2
- 208000002409 gliosarcoma Diseases 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 230000035876 healing Effects 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 108010037743 hemoglobin glutamer-200 Proteins 0.000 description 2
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 2
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 2
- 230000003301 hydrolyzing effect Effects 0.000 description 2
- 229920001477 hydrophilic polymer Polymers 0.000 description 2
- 238000009802 hysterectomy Methods 0.000 description 2
- 238000002513 implantation Methods 0.000 description 2
- 238000010874 in vitro model Methods 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 208000024312 invasive carcinoma Diseases 0.000 description 2
- 229960004768 irinotecan Drugs 0.000 description 2
- UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 description 2
- 230000000302 ischemic effect Effects 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 238000011031 large-scale manufacturing process Methods 0.000 description 2
- 201000005264 laryngeal carcinoma Diseases 0.000 description 2
- 208000032839 leukemia Diseases 0.000 description 2
- 108010049645 liposome-encapsulated hemoglobin Proteins 0.000 description 2
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 2
- 239000008204 material by function Substances 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 230000002503 metabolic effect Effects 0.000 description 2
- 230000001394 metastastic effect Effects 0.000 description 2
- 206010061289 metastatic neoplasm Diseases 0.000 description 2
- 108010042832 metmyoglobin azide Proteins 0.000 description 2
- 238000000329 molecular dynamics simulation Methods 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- 230000000877 morphologic effect Effects 0.000 description 2
- 210000002200 mouth mucosa Anatomy 0.000 description 2
- 238000002703 mutagenesis Methods 0.000 description 2
- 231100000350 mutagenesis Toxicity 0.000 description 2
- 239000002088 nanocapsule Substances 0.000 description 2
- 239000002539 nanocarrier Substances 0.000 description 2
- 239000002077 nanosphere Substances 0.000 description 2
- 231100000417 nephrotoxicity Toxicity 0.000 description 2
- 230000007694 nephrotoxicity Effects 0.000 description 2
- MDJFHRLTPRPZLY-UHFFFAOYSA-N nimorazole Chemical compound [O-][N+](=O)C1=CN=CN1CCN1CCOCC1 MDJFHRLTPRPZLY-UHFFFAOYSA-N 0.000 description 2
- 229960004918 nimorazole Drugs 0.000 description 2
- 238000010606 normalization Methods 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 230000001590 oxidative effect Effects 0.000 description 2
- 108010050846 oxymyoglobin Proteins 0.000 description 2
- 201000002528 pancreatic cancer Diseases 0.000 description 2
- 208000008443 pancreatic carcinoma Diseases 0.000 description 2
- 230000035515 penetration Effects 0.000 description 2
- 230000010412 perfusion Effects 0.000 description 2
- 210000003800 pharynx Anatomy 0.000 description 2
- 230000008288 physiological mechanism Effects 0.000 description 2
- 229920002854 poly(ethyl ethoxyethylene phosphate) polymer Polymers 0.000 description 2
- 229920001173 poly(trimethylene carbonate)-block-poly(l-glutamic acid) Polymers 0.000 description 2
- 238000006116 polymerization reaction Methods 0.000 description 2
- 239000011148 porous material Substances 0.000 description 2
- 229940002612 prodrug Drugs 0.000 description 2
- 239000000651 prodrug Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 230000002035 prolonged effect Effects 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000011002 quantification Methods 0.000 description 2
- XSCHRSMBECNVNS-UHFFFAOYSA-N quinoxaline Chemical compound N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 description 2
- 230000000306 recurrent effect Effects 0.000 description 2
- 230000000284 resting effect Effects 0.000 description 2
- 230000002000 scavenging effect Effects 0.000 description 2
- 150000003330 sebacic acids Chemical class 0.000 description 2
- 230000009919 sequestration Effects 0.000 description 2
- 238000001542 size-exclusion chromatography Methods 0.000 description 2
- 230000002269 spontaneous effect Effects 0.000 description 2
- 206010041823 squamous cell carcinoma Diseases 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 238000001370 static light scattering Methods 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 230000002123 temporal effect Effects 0.000 description 2
- 230000004797 therapeutic response Effects 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 230000007704 transition Effects 0.000 description 2
- 230000001960 triggered effect Effects 0.000 description 2
- 230000036326 tumor accumulation Effects 0.000 description 2
- 230000005751 tumor progression Effects 0.000 description 2
- 238000000108 ultra-filtration Methods 0.000 description 2
- 238000000870 ultraviolet spectroscopy Methods 0.000 description 2
- 208000010570 urinary bladder carcinoma Diseases 0.000 description 2
- 230000003966 vascular damage Effects 0.000 description 2
- 230000025033 vasoconstriction Effects 0.000 description 2
- 230000003612 virological effect Effects 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- PAPBSGBWRJIAAV-UHFFFAOYSA-N ε-Caprolactone Chemical compound O=C1CCCCCO1 PAPBSGBWRJIAAV-UHFFFAOYSA-N 0.000 description 2
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- INGWEZCOABYORO-UHFFFAOYSA-N 2-(furan-2-yl)-7-methyl-1h-1,8-naphthyridin-4-one Chemical class N=1C2=NC(C)=CC=C2C(O)=CC=1C1=CC=CO1 INGWEZCOABYORO-UHFFFAOYSA-N 0.000 description 1
- VNXMFQWTDCWMDQ-UHFFFAOYSA-N 5-methyloxepan-2-one Chemical compound CC1CCOC(=O)CC1 VNXMFQWTDCWMDQ-UHFFFAOYSA-N 0.000 description 1
- 208000003200 Adenoma Diseases 0.000 description 1
- 108020004491 Antisense DNA Proteins 0.000 description 1
- 108020000948 Antisense Oligonucleotides Proteins 0.000 description 1
- 108020005544 Antisense RNA Proteins 0.000 description 1
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
- 238000009010 Bradford assay Methods 0.000 description 1
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 201000011057 Breast sarcoma Diseases 0.000 description 1
- OWNRRUFOJXFKCU-UHFFFAOYSA-N Bromadiolone Chemical compound C=1C=C(C=2C=CC(Br)=CC=2)C=CC=1C(O)CC(C=1C(OC2=CC=CC=C2C=1O)=O)C1=CC=CC=C1 OWNRRUFOJXFKCU-UHFFFAOYSA-N 0.000 description 1
- KLWPJMFMVPTNCC-UHFFFAOYSA-N Camptothecin Natural products CCC1(O)C(=O)OCC2=C1C=C3C4Nc5ccccc5C=C4CN3C2=O KLWPJMFMVPTNCC-UHFFFAOYSA-N 0.000 description 1
- 241000282465 Canis Species 0.000 description 1
- 208000005623 Carcinogenesis Diseases 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 230000005778 DNA damage Effects 0.000 description 1
- 231100000277 DNA damage Toxicity 0.000 description 1
- 108010092160 Dactinomycin Proteins 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 244000179525 Dracocephalum moldavica Species 0.000 description 1
- 208000007033 Dysgerminoma Diseases 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- 108010044495 Fetal Hemoglobin Proteins 0.000 description 1
- 238000006424 Flood reaction Methods 0.000 description 1
- 229910001218 Gallium arsenide Inorganic materials 0.000 description 1
- 101000987586 Homo sapiens Eosinophil peroxidase Proteins 0.000 description 1
- 101000920686 Homo sapiens Erythropoietin Proteins 0.000 description 1
- 206010058179 Hypertensive emergency Diseases 0.000 description 1
- IMQLKJBTEOYOSI-GPIVLXJGSA-N Inositol-hexakisphosphate Chemical compound OP(O)(=O)O[C@H]1[C@H](OP(O)(O)=O)[C@@H](OP(O)(O)=O)[C@H](OP(O)(O)=O)[C@H](OP(O)(O)=O)[C@@H]1OP(O)(O)=O IMQLKJBTEOYOSI-GPIVLXJGSA-N 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
- 235000021534 Mangelwurzel Nutrition 0.000 description 1
- 206010027406 Mesothelioma Diseases 0.000 description 1
- 241000478714 Microchirita viola Species 0.000 description 1
- 241000995105 Mycobacterium phage Henry Species 0.000 description 1
- 206010028629 Myoglobinuria Diseases 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 206010029260 Neuroblastoma Diseases 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 108010064719 Oxyhemoglobins Proteins 0.000 description 1
- IMQLKJBTEOYOSI-UHFFFAOYSA-N Phytic acid Natural products OP(O)(=O)OC1C(OP(O)(O)=O)C(OP(O)(O)=O)C(OP(O)(O)=O)C(OP(O)(O)=O)C1OP(O)(O)=O IMQLKJBTEOYOSI-UHFFFAOYSA-N 0.000 description 1
- 229920000475 Poly(ethylene oxide)-block-polycaprolactone Polymers 0.000 description 1
- 229920000471 Poly(ethylene oxide)-block-polylactide Polymers 0.000 description 1
- 229920002732 Polyanhydride Polymers 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 229920002367 Polyisobutene Polymers 0.000 description 1
- 229920001710 Polyorthoester Polymers 0.000 description 1
- CKIHZSGJPSDCNC-UHFFFAOYSA-N Quindoxin Chemical class C1=CC=C2N([O-])C=C[N+](=O)C2=C1 CKIHZSGJPSDCNC-UHFFFAOYSA-N 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 208000015634 Rectal Neoplasms Diseases 0.000 description 1
- 201000000582 Retinoblastoma Diseases 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- 108010016797 Sickle Hemoglobin Proteins 0.000 description 1
- 244000258044 Solanum gilo Species 0.000 description 1
- 235000018650 Solanum gilo Nutrition 0.000 description 1
- 206010041848 Squamous cell carcinoma of the cervix Diseases 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- OIRDTQYFTABQOQ-UHTZMRCNSA-N Vidarabine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@@H]1O OIRDTQYFTABQOQ-UHTZMRCNSA-N 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
- 208000008383 Wilms tumor Diseases 0.000 description 1
- 150000003926 acrylamides Chemical class 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-M acrylate group Chemical group C(C=C)(=O)[O-] NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 1
- 150000001252 acrylic acid derivatives Chemical class 0.000 description 1
- RJURFGZVJUQBHK-IIXSONLDSA-N actinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-IIXSONLDSA-N 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 208000009956 adenocarcinoma Diseases 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 229940009456 adriamycin Drugs 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 230000002152 alkylating effect Effects 0.000 description 1
- 230000001772 anti-angiogenic effect Effects 0.000 description 1
- 230000000692 anti-sense effect Effects 0.000 description 1
- 239000003816 antisense DNA Substances 0.000 description 1
- 239000000074 antisense oligonucleotide Substances 0.000 description 1
- 238000012230 antisense oligonucleotides Methods 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 239000002473 artificial blood Substances 0.000 description 1
- 239000012752 auxiliary agent Substances 0.000 description 1
- 210000001142 back Anatomy 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 238000006065 biodegradation reaction Methods 0.000 description 1
- 230000007227 biological adhesion Effects 0.000 description 1
- 230000008033 biological extinction Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 239000012503 blood component Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 229910052796 boron Inorganic materials 0.000 description 1
- 239000005388 borosilicate glass Substances 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- HJJVPARKXDDIQD-UHFFFAOYSA-N bromuconazole Chemical compound ClC1=CC(Cl)=CC=C1C1(CN2N=CN=C2)OCC(Br)C1 HJJVPARKXDDIQD-UHFFFAOYSA-N 0.000 description 1
- 230000005587 bubbling Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000007975 buffered saline Substances 0.000 description 1
- 230000003139 buffering effect Effects 0.000 description 1
- 235000019437 butane-1,3-diol Nutrition 0.000 description 1
- VSJKWCGYPAHWDS-FQEVSTJZSA-N camptothecin Chemical compound C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-FQEVSTJZSA-N 0.000 description 1
- 229940127093 camptothecin Drugs 0.000 description 1
- 239000003560 cancer drug Substances 0.000 description 1
- 230000036952 cancer formation Effects 0.000 description 1
- 230000005907 cancer growth Effects 0.000 description 1
- 210000000234 capsid Anatomy 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000022131 cell cycle Effects 0.000 description 1
- 230000019522 cellular metabolic process Effects 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 239000013043 chemical agent Substances 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 229960003920 cocaine Drugs 0.000 description 1
- 229960001338 colchicine Drugs 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 230000001010 compromised effect Effects 0.000 description 1
- 238000000942 confocal micrograph Methods 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 230000009146 cooperative binding Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 229940109239 creatinine Drugs 0.000 description 1
- 229920006037 cross link polymer Polymers 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 229960000640 dactinomycin Drugs 0.000 description 1
- 238000011475 definitive radiotherapy Methods 0.000 description 1
- 238000009110 definitive therapy Methods 0.000 description 1
- 239000007857 degradation product Substances 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 125000004386 diacrylate group Chemical group 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- AFOSIXZFDONLBT-UHFFFAOYSA-N divinyl sulfone Chemical group C=CS(=O)(=O)C=C AFOSIXZFDONLBT-UHFFFAOYSA-N 0.000 description 1
- VSJKWCGYPAHWDS-UHFFFAOYSA-N dl-camptothecin Natural products C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)C5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-UHFFFAOYSA-N 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 239000013583 drug formulation Substances 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 239000012149 elution buffer Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000008393 encapsulating agent Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 230000007071 enzymatic hydrolysis Effects 0.000 description 1
- 238000006047 enzymatic hydrolysis reaction Methods 0.000 description 1
- 230000003628 erosive effect Effects 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 230000004992 fission Effects 0.000 description 1
- 238000000684 flow cytometry Methods 0.000 description 1
- 238000012921 fluorescence analysis Methods 0.000 description 1
- 230000007760 free radical scavenging Effects 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 102000018146 globin Human genes 0.000 description 1
- 108060003196 globin Proteins 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 210000003128 head Anatomy 0.000 description 1
- 102000044890 human EPO Human genes 0.000 description 1
- 239000000017 hydrogel Substances 0.000 description 1
- 229920001480 hydrophilic copolymer Polymers 0.000 description 1
- 150000002433 hydrophilic molecules Chemical class 0.000 description 1
- 229920001600 hydrophobic polymer Polymers 0.000 description 1
- 238000007654 immersion Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 150000002484 inorganic compounds Chemical class 0.000 description 1
- 229910010272 inorganic material Inorganic materials 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 238000000111 isothermal titration calorimetry Methods 0.000 description 1
- 238000012933 kinetic analysis Methods 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 208000037841 lung tumor Diseases 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 230000002934 lysing effect Effects 0.000 description 1
- 238000002595 magnetic resonance imaging Methods 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 201000005857 malignant hypertension Diseases 0.000 description 1
- 208000026037 malignant tumor of neck Diseases 0.000 description 1
- 210000004216 mammary stem cell Anatomy 0.000 description 1
- 238000013507 mapping Methods 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 238000000816 matrix-assisted laser desorption--ionisation Methods 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 206010027191 meningioma Diseases 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 150000002734 metacrylic acid derivatives Chemical class 0.000 description 1
- FQPSGWSUVKBHSU-UHFFFAOYSA-N methacrylamide Chemical class CC(=C)C(N)=O FQPSGWSUVKBHSU-UHFFFAOYSA-N 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- CXKWCBBOMKCUKX-UHFFFAOYSA-M methylene blue Chemical compound [Cl-].C1=CC(N(C)C)=CC2=[S+]C3=CC(N(C)C)=CC=C3N=C21 CXKWCBBOMKCUKX-UHFFFAOYSA-M 0.000 description 1
- 229960000907 methylthioninium chloride Drugs 0.000 description 1
- 210000004088 microvessel Anatomy 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 230000033607 mismatch repair Effects 0.000 description 1
- 230000000116 mitigating effect Effects 0.000 description 1
- 201000010225 mixed cell type cancer Diseases 0.000 description 1
- 208000029638 mixed neoplasm Diseases 0.000 description 1
- 230000003990 molecular pathway Effects 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 210000004165 myocardium Anatomy 0.000 description 1
- 210000003739 neck Anatomy 0.000 description 1
- 230000003589 nefrotoxic effect Effects 0.000 description 1
- 231100000381 nephrotoxic Toxicity 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000000346 nonvolatile oil Substances 0.000 description 1
- 239000002777 nucleoside Substances 0.000 description 1
- 150000003833 nucleoside derivatives Chemical class 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000008816 organ damage Effects 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 230000010627 oxidative phosphorylation Effects 0.000 description 1
- 230000036542 oxidative stress Effects 0.000 description 1
- 230000000242 pagocytic effect Effects 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 238000001126 phototherapy Methods 0.000 description 1
- 229940068041 phytic acid Drugs 0.000 description 1
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 description 1
- 229920000725 poly(menthide) polymer Polymers 0.000 description 1
- 229920002627 poly(phosphazenes) Polymers 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920002959 polymer blend Polymers 0.000 description 1
- 102000040430 polynucleotide Human genes 0.000 description 1
- 108091033319 polynucleotide Proteins 0.000 description 1
- 229920001451 polypropylene glycol Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000000135 prohibitive effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 125000006308 propyl amino group Chemical group 0.000 description 1
- 238000002731 protein assay Methods 0.000 description 1
- 235000004252 protein component Nutrition 0.000 description 1
- 239000012460 protein solution Substances 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 238000006862 quantum yield reaction Methods 0.000 description 1
- 238000010526 radical polymerization reaction Methods 0.000 description 1
- 229920005604 random copolymer Polymers 0.000 description 1
- 230000006950 reactive oxygen species formation Effects 0.000 description 1
- 206010038038 rectal cancer Diseases 0.000 description 1
- 201000001275 rectum cancer Diseases 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000008844 regulatory mechanism Effects 0.000 description 1
- 239000000310 rehydration solution Substances 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 230000004043 responsiveness Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 1
- 210000003079 salivary gland Anatomy 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000005204 segregation Methods 0.000 description 1
- 208000007056 sickle cell anemia Diseases 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- ZFMRLFXUPVQYAU-UHFFFAOYSA-N sodium 5-[[4-[4-[(7-amino-1-hydroxy-3-sulfonaphthalen-2-yl)diazenyl]phenyl]phenyl]diazenyl]-2-hydroxybenzoic acid Chemical compound C1=CC(=CC=C1C2=CC=C(C=C2)N=NC3=C(C=C4C=CC(=CC4=C3O)N)S(=O)(=O)O)N=NC5=CC(=C(C=C5)O)C(=O)O.[Na+] ZFMRLFXUPVQYAU-UHFFFAOYSA-N 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 210000000603 stem cell niche Anatomy 0.000 description 1
- 201000011549 stomach cancer Diseases 0.000 description 1
- 210000003699 striated muscle Anatomy 0.000 description 1
- 231100000456 subacute toxicity Toxicity 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- TXEYQDLBPFQVAA-UHFFFAOYSA-N tetrafluoromethane Chemical compound FC(F)(F)F TXEYQDLBPFQVAA-UHFFFAOYSA-N 0.000 description 1
- 230000010512 thermal transition Effects 0.000 description 1
- 238000000015 thermotherapy Methods 0.000 description 1
- KSBAEPSJVUENNK-UHFFFAOYSA-L tin(ii) 2-ethylhexanoate Chemical compound [Sn+2].CCCCC(CC)C([O-])=O.CCCCC(CC)C([O-])=O KSBAEPSJVUENNK-UHFFFAOYSA-L 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 229920000428 triblock copolymer Polymers 0.000 description 1
- 238000002371 ultraviolet--visible spectrum Methods 0.000 description 1
- 239000002691 unilamellar liposome Substances 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- 201000011531 vascular cancer Diseases 0.000 description 1
- 230000006442 vascular tone Effects 0.000 description 1
- 230000002227 vasoactive effect Effects 0.000 description 1
- 229940124549 vasodilator Drugs 0.000 description 1
- 239000003071 vasodilator agent Substances 0.000 description 1
- 210000003462 vein Anatomy 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
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 238000003260 vortexing Methods 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/1703—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- A61K38/1709—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
- A61K41/0038—Radiosensitizing, i.e. administration of pharmaceutical agents that enhance the effect of radiotherapy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
- A61K31/713—Double-stranded nucleic acids or oligonucleotides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/41—Porphyrin- or corrin-ring-containing peptides
- A61K38/42—Haemoglobins; Myoglobins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
- A61K9/0026—Blood substitute; Oxygen transporting formulations; Plasma extender
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
- A61K9/1271—Non-conventional liposomes, e.g. PEGylated liposomes or liposomes coated or grafted with polymers
- A61K9/1273—Polymersomes; Liposomes with polymerisable or polymerised bilayer-forming substances
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N5/00—Radiation therapy
- A61N5/10—X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B65—CONVEYING; PACKING; STORING; HANDLING THIN OR FILAMENTARY MATERIAL
- B65D—CONTAINERS FOR STORAGE OR TRANSPORT OF ARTICLES OR MATERIALS, e.g. BAGS, BARRELS, BOTTLES, BOXES, CANS, CARTONS, CRATES, DRUMS, JARS, TANKS, HOPPERS, FORWARDING CONTAINERS; ACCESSORIES, CLOSURES, OR FITTINGS THEREFOR; PACKAGING ELEMENTS; PACKAGES
- B65D25/00—Details of other kinds or types of rigid or semi-rigid containers
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/70—Mechanisms involved in disease identification
- G01N2800/7038—Hypoxia
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Immunology (AREA)
- Gastroenterology & Hepatology (AREA)
- Dispersion Chemistry (AREA)
- Zoology (AREA)
- Biomedical Technology (AREA)
- Biochemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Marine Sciences & Fisheries (AREA)
- Radiology & Medical Imaging (AREA)
- Pathology (AREA)
- Mechanical Engineering (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Hematology (AREA)
- Dermatology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Claims (13)
1. Middel med høj oxygenaffinitet til anvendelse i en fremgangsmåde til øgning af virkning af stråling eller kemoterapi anvendt til en tumor hos et individ, hvilken fremgangsmåde omfatter: afgivelse af midlet med høj oxygenaffinitet til tumoren ved administration til individet af en oxygenbærer, der inkorporerer midlet med høj oxygenaffinitet, hvor: midlet med høj oxygenaffinitet omfatter en myoglobinsammensætning; og oxygenpartialtrykgradientegenskaber for midlet med høj oxygenaffinitet er således, at oxygen frigives fra midlet med høj oxygenaffinitet ved oxygenspændinger på mindre end 10 mmHg, hvor det frigivne oxygen diffunderer ud af oxygenbæreren, mens midlet med høj oxygenaffinitet forbliver inde i oxygenbæreren.
2. Middel med høj oxygenaffinitet til anvendelse ifølge krav 1, hvor midlet med høj oxygenaffinitet har et P50 for oxygen på omkring 2-3 mmHg.
3. Middel med høj oxygenaffinitet til anvendelse ifølge krav 2, hvor midlet med høj oxygenaffinitet omfatter ét eller flere af umodificeret human myoglobin, umodificeret myoglobin fra andre biologiske arter og kemisk eller genetisk modificeret myoglobin fra mennesker eller fra andre biologiske arter.
4. Middel med høj oxygenaffinitet til anvendelse ifølge krav 2, hvor midlet med høj oxygenaffinitet er en samvirkende oxygenbinder eller en lineær oxygenbinder.
5. Middel med høj oxygenaffinitet til anvendelse ifølge krav 2, hvor oxygenpartialtrykgradientegenskaber for midlet med høj oxygenaffinitet er således, at oxygen bindes tæt af midlet med høj oxygenaffinitet under cirkulation i en blodbane.
6. Middel med høj oxygenaffinitet til anvendelse ifølge krav 1, hvor midlet med høj oxygenaffinitet er PEGyleret eller polymeriseret.
7. Middel med høj oxygenaffinitet til anvendelse ifølge krav 1, hvor midlet med høj oxygenaffinitet er indkapslet i oxygenbæreren, og hvor oxygenbæreren omfatter et bærervehikel, der beskytter midlet med høj oxygenaffinitet mod at blive frigivet i en blodbane.
8. Middel med høj oxygenaffinitet til anvendelse ifølge krav 1, hvor midlet med høj oxygenaffinitet er co-indkapslet i et bærervehikel med mindst ét andet strålingssensibiliserende eller kemoterapeutisk middel.
9. Middel med høj oxygenaffinitet til anvendelse ifølge krav 7, hvor bærervehiklet er valgt fra én af en nanopartikelbaseret vehikel, en flydende vesikel, en syntetisk polymervesikel eller et uni- eller multi-lamellært polymersom.
10. Middel med høj oxygenaffinitet til anvendelse ifølge krav 7, hvor bærervehiklet er en veksikel, og hvor midlet med høj oxygenaffinitet er inde i en vandig kerne eller en membrandel af vesiklen.
11. Middel med høj oxygenaffinitet til anvendelse ifølge krav 7, hvor bærervehiklet omfatter en flerhed af bionedbrydelige polymerer.
12. Kit, der omfatter: en første beholder og en anden container; hvor den første beholder omfatter midlet med høj oxygenaffinitet ifølge krav 1, og hvor den anden beholder omfatter en rehydreringsblanding.
13. Middel med høj oxygenaffinitet til anvendelse ifølge krav 1, hvor administration til individet af oxygenbæreren, hvori midlet med høj oxygenaffinitet er inkorporeret, omfatter administration af oxygenbæreren intravenøst, via inhalation, topisk, per rectum, per vagina, transdermalt, subkutant, intraperitonealt, intratekalt, intramuskulært eller oralt.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161430628P | 2011-01-07 | 2011-01-07 | |
| US201161435886P | 2011-01-25 | 2011-01-25 | |
| PCT/US2012/020680 WO2012094679A2 (en) | 2011-01-07 | 2012-01-09 | Compositions and methods for delivery of high-affinity oxygen binding agents to tumors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DK2661275T3 true DK2661275T3 (da) | 2019-04-15 |
Family
ID=46458007
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK12732165.1T DK2661275T3 (da) | 2011-01-07 | 2012-01-09 | Sammensætninger og fremgangsmåder til indgivelse af bindingsmidlet med høj oxygenaffinitet til tumorer |
Country Status (6)
| Country | Link |
|---|---|
| US (2) | US20130177641A1 (da) |
| EP (1) | EP2661275B1 (da) |
| DK (1) | DK2661275T3 (da) |
| ES (1) | ES2718308T3 (da) |
| PT (1) | PT2661275T (da) |
| WO (1) | WO2012094679A2 (da) |
Families Citing this family (34)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3922643A1 (en) | 2013-01-07 | 2021-12-15 | Omniox, Inc. | Polymeric forms of h-nox proteins |
| FR3002146B1 (fr) * | 2013-02-15 | 2016-03-04 | Hemarina | Utilisation d'hemoglobine d'annelides pour traiter les cancers |
| US10159688B2 (en) | 2013-03-15 | 2018-12-25 | M. Alphabet 3, L.L.C. | Methods and compositions for enhancing oxygen levels in tissues |
| CA2957552C (en) * | 2014-08-08 | 2024-01-16 | Vindico Nanobiotechnology, Llc | Compositions and methods for inducing nanoparticle-mediated microvascular embolization of tumors |
| CA2969684A1 (en) * | 2014-12-05 | 2016-06-09 | Vindico Nanobiotechnology, Llc | Compositions and methods for inducing nanoparticle-mediated microvascular embolization of tumors |
| SG10201908269SA (en) | 2015-03-17 | 2019-10-30 | Omniox Inc | Modulation of tumor immunity by protein-mediated o2 delivery |
| US10456452B2 (en) | 2015-07-02 | 2019-10-29 | Poseida Therapeutics, Inc. | Compositions and methods for improved encapsulation of functional proteins in polymeric vesicles |
| WO2017039435A1 (en) | 2015-08-28 | 2017-03-09 | Rijksuniversiteit Groningen | Means and methods for sustained oxygen release in situ |
| US9855445B2 (en) | 2016-04-01 | 2018-01-02 | Varian Medical Systems, Inc. | Radiation therapy systems and methods for delivering doses to a target volume |
| ES2865481T3 (es) | 2016-04-29 | 2021-10-15 | Poseida Therapeutics Inc | Micelas basadas en poli(histidina) para la complejación y el aporte de proteínas y ácidos nucleicos |
| CN109803685B (zh) | 2016-08-16 | 2023-02-17 | 瑞士苏黎世联邦理工学院 | 跨膜pH-梯度聚合物囊泡及其制备方法 |
| CA3105873A1 (en) | 2016-09-30 | 2018-04-05 | Poseida Therapeutics, Inc. | Modified stem cell memory t cells, methods of making and methods of using same |
| US20190119636A1 (en) | 2017-10-23 | 2019-04-25 | Poseida Therapeutics, Inc. | Modified stem cell memory t cells, methods of making and methods of using same |
| DK3523325T3 (da) | 2016-10-06 | 2025-11-10 | Poseida Therapeutics Inc | Inducerbare caspaser og fremgangsmåder til anvendelse |
| US11590364B2 (en) | 2017-07-21 | 2023-02-28 | Varian Medical Systems International Ag | Material inserts for radiation therapy |
| US11712579B2 (en) | 2017-07-21 | 2023-08-01 | Varian Medical Systems, Inc. | Range compensators for radiation therapy |
| US10092774B1 (en) | 2017-07-21 | 2018-10-09 | Varian Medical Systems International, AG | Dose aspects of radiation therapy planning and treatment |
| US10549117B2 (en) | 2017-07-21 | 2020-02-04 | Varian Medical Systems, Inc | Geometric aspects of radiation therapy planning and treatment |
| US10843011B2 (en) | 2017-07-21 | 2020-11-24 | Varian Medical Systems, Inc. | Particle beam gun control systems and methods |
| US10183179B1 (en) | 2017-07-21 | 2019-01-22 | Varian Medical Systems, Inc. | Triggered treatment systems and methods |
| CN110945076B (zh) | 2017-09-12 | 2023-10-17 | 苏黎士联邦理工大学 | 用于定量体液中的氨的跨膜pH梯度聚合物囊泡 |
| US20200261495A1 (en) * | 2017-09-24 | 2020-08-20 | Aodh Lifesciences Private Limited | Liquid oxygen encapsulation and methods to administer intravascular liquid oxygen |
| US10329543B2 (en) | 2017-10-23 | 2019-06-25 | Poseida Therapeutics, Inc. | Modified stem cell memory T cells, methods of making and methods of using same |
| US11007381B2 (en) | 2017-11-16 | 2021-05-18 | Varian Medical Systems, Inc | Increased beam output and dynamic field shaping for radiotherapy system |
| JP7398115B2 (ja) | 2017-12-22 | 2023-12-14 | ノース カロライナ ステート ユニバーシティ | ポリマーフルオロフォア、それを含む組成物、ならびにその調製および使用方法 |
| US11116995B2 (en) | 2019-03-06 | 2021-09-14 | Varian Medical Systems, Inc. | Radiation treatment planning based on dose rate |
| US10814144B2 (en) | 2019-03-06 | 2020-10-27 | Varian Medical Systems, Inc. | Radiation treatment based on dose rate |
| US10918886B2 (en) | 2019-06-10 | 2021-02-16 | Varian Medical Systems, Inc. | Flash therapy treatment planning and oncology information system having dose rate prescription and dose rate mapping |
| US11576978B2 (en) * | 2019-07-19 | 2023-02-14 | Cheer Global Limited | Hemoglobin-based therapeutic agents |
| US12390662B2 (en) | 2020-04-02 | 2025-08-19 | Siemens Healthineers International Ag | System and method for proton therapy treatment planning with proton energy and spot optimization |
| US11865361B2 (en) | 2020-04-03 | 2024-01-09 | Varian Medical Systems, Inc. | System and method for scanning pattern optimization for flash therapy treatment planning |
| US11541252B2 (en) | 2020-06-23 | 2023-01-03 | Varian Medical Systems, Inc. | Defining dose rate for pencil beam scanning |
| US11957934B2 (en) | 2020-07-01 | 2024-04-16 | Siemens Healthineers International Ag | Methods and systems using modeling of crystalline materials for spot placement for radiation therapy |
| US12064645B2 (en) | 2020-07-02 | 2024-08-20 | Siemens Healthineers International Ag | Methods and systems used for planning radiation treatment |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5833974A (en) * | 1996-04-17 | 1998-11-10 | Teicher; Beverly A. | Method of enhancing the effective life of oxygen-delivery agents |
| DE10031741A1 (de) * | 2000-06-29 | 2002-01-17 | Sanguibio Tech Ag | Einen Sauerstoffträger, ausgewählt aus Hämoglobin oder Hämoglobin- und Myoglobin-enthaltende Zubereitung als Externum zur natürlichen Regeneration der Haut bei Sauerstoff-Mangel |
| US20030153491A1 (en) * | 2002-01-11 | 2003-08-14 | Winslow Robert M. | Methods and compositions for oxygen transport comprising a high oxygen affinity modified hemoglobin |
| DE10212321A1 (de) * | 2002-03-20 | 2003-10-09 | Sanguibio Tech Ag | Verwendung eines oder mehrerer von Plasma und Zellwandbestandteilen befreiten natürlichen oder modifizierten Sauerstoffbinder zur externen Behandlung offener, insbesondere chronischer Wunden |
| US20080102128A1 (en) * | 2006-07-28 | 2008-05-01 | Flamel Technologies, Inc. | Modified-release microparticles based on amphiphilic copolymer and on active principles(s) and pharmaceutical formulations comprising them |
| US8420118B2 (en) * | 2009-09-10 | 2013-04-16 | The Board Of Regents Of The University Of Oklahoma | Anionic lipids and lipid nano-structures and methods of producing and using same |
| US8808748B2 (en) * | 2010-04-20 | 2014-08-19 | Vindico NanoBio Technology Inc. | Biodegradable nanoparticles as novel hemoglobin-based oxygen carriers and methods of using the same |
-
2012
- 2012-01-09 ES ES12732165T patent/ES2718308T3/es active Active
- 2012-01-09 WO PCT/US2012/020680 patent/WO2012094679A2/en not_active Ceased
- 2012-01-09 EP EP12732165.1A patent/EP2661275B1/en active Active
- 2012-01-09 PT PT12732165T patent/PT2661275T/pt unknown
- 2012-01-09 DK DK12732165.1T patent/DK2661275T3/da active
- 2012-01-09 US US13/508,271 patent/US20130177641A1/en not_active Abandoned
-
2014
- 2014-04-25 US US14/261,540 patent/US20140255477A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| US20140255477A1 (en) | 2014-09-11 |
| ES2718308T3 (es) | 2019-07-01 |
| EP2661275A2 (en) | 2013-11-13 |
| PT2661275T (pt) | 2019-04-24 |
| WO2012094679A3 (en) | 2012-10-26 |
| EP2661275B1 (en) | 2019-01-02 |
| WO2012094679A2 (en) | 2012-07-12 |
| EP2661275A4 (en) | 2014-07-23 |
| US20130177641A1 (en) | 2013-07-11 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP2661275B1 (en) | Compositions and methods for delivery of high-affinity oxygen binding agents to tumors | |
| US20200338361A1 (en) | Compositions and methods for inducing nanoparticle-mediated microvascular embolization for tumors | |
| US20200138716A1 (en) | Compositions and methods for inducing nanoparticle-mediated microvascular embolization of tumors | |
| US9533027B2 (en) | Biodegradable nanoparticles as novel hemoglobin-based oxygen carriers and methods of using the same | |
| EP3177713B1 (en) | Compositions and their use for inducing nanoparticle-mediated microvascular embolization of tumors | |
| Meng et al. | Logical design and application of prodrug platforms | |
| Taha et al. | Critical quality attributes in the development of therapeutic nanomedicines toward clinical translation | |
| US20120164065A1 (en) | Method and composition for treating cancer | |
| Liu et al. | Nano-Based strategies aiming at tumor microenvironment for improved Cancer therapy | |
| AU2015204358B2 (en) | Biodegradable nanoparticles as novel hemoglobin-based oxygen carriers and methods of using the same | |
| Yamamoto et al. | Systemic administration of hemoglobin vesicle elevates tumor tissue oxygen tension and modifies tumor response to irradiation | |
| HK1239746B (en) | Compositions and their use for inducing nanoparticle-mediated microvascular embolization of tumors | |
| HK1239746A1 (en) | Compositions and their use for inducing nanoparticle-mediated microvascular embolization of tumors | |
| Kydd | Drug Delivery Systems and Combination Therapy for Oncomedicine |