JP5814363B2 - 細胞の原形質体に由来するマイクロベシクル及びその用途 - Google Patents
細胞の原形質体に由来するマイクロベシクル及びその用途 Download PDFInfo
- Publication number
- JP5814363B2 JP5814363B2 JP2013518258A JP2013518258A JP5814363B2 JP 5814363 B2 JP5814363 B2 JP 5814363B2 JP 2013518258 A JP2013518258 A JP 2013518258A JP 2013518258 A JP2013518258 A JP 2013518258A JP 5814363 B2 JP5814363 B2 JP 5814363B2
- Authority
- JP
- Japan
- Prior art keywords
- microvesicles
- derived
- cell
- microvesicle
- protoplast
- 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
- 210000001938 protoplast Anatomy 0.000 title claims description 270
- 210000004027 cell Anatomy 0.000 claims description 248
- 239000000126 substance Substances 0.000 claims description 173
- 238000000034 method Methods 0.000 claims description 77
- 108090000623 proteins and genes Proteins 0.000 claims description 75
- 108020001507 fusion proteins Proteins 0.000 claims description 66
- 102000037865 fusion proteins Human genes 0.000 claims description 66
- 102000004169 proteins and genes Human genes 0.000 claims description 65
- 230000001580 bacterial effect Effects 0.000 claims description 59
- 206010028980 Neoplasm Diseases 0.000 claims description 57
- 201000011510 cancer Diseases 0.000 claims description 54
- 210000002421 cell wall Anatomy 0.000 claims description 46
- 239000000725 suspension Substances 0.000 claims description 39
- 210000000170 cell membrane Anatomy 0.000 claims description 36
- 239000002246 antineoplastic agent Substances 0.000 claims description 22
- 239000008194 pharmaceutical composition Substances 0.000 claims description 14
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 12
- 239000003446 ligand Substances 0.000 claims description 10
- 230000001939 inductive effect Effects 0.000 claims description 8
- 230000008569 process Effects 0.000 claims description 8
- 210000003000 inclusion body Anatomy 0.000 claims description 7
- 210000004692 intercellular junction Anatomy 0.000 claims description 7
- 108010027796 Membrane Fusion Proteins Proteins 0.000 claims description 3
- 102000018897 Membrane Fusion Proteins Human genes 0.000 claims description 3
- 241000894006 Bacteria Species 0.000 description 78
- 210000001519 tissue Anatomy 0.000 description 70
- 229960005486 vaccine Drugs 0.000 description 66
- 101800003838 Epidermal growth factor Proteins 0.000 description 65
- 235000018102 proteins Nutrition 0.000 description 60
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 60
- 102400001368 Epidermal growth factor Human genes 0.000 description 59
- 229940116977 epidermal growth factor Drugs 0.000 description 59
- 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 54
- 230000001225 therapeutic effect Effects 0.000 description 52
- 241000588724 Escherichia coli Species 0.000 description 47
- 238000011282 treatment Methods 0.000 description 42
- 239000012528 membrane Substances 0.000 description 40
- 238000011068 loading method Methods 0.000 description 39
- 201000010099 disease Diseases 0.000 description 37
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 37
- 238000004519 manufacturing process Methods 0.000 description 37
- 238000005406 washing Methods 0.000 description 37
- 210000004379 membrane Anatomy 0.000 description 36
- 108091007433 antigens Proteins 0.000 description 34
- 102000036639 antigens Human genes 0.000 description 34
- 102000001301 EGF receptor Human genes 0.000 description 32
- 239000000427 antigen Substances 0.000 description 32
- 238000003745 diagnosis Methods 0.000 description 32
- 239000013612 plasmid Substances 0.000 description 32
- 241000699670 Mus sp. Species 0.000 description 31
- 239000000243 solution Substances 0.000 description 30
- 108060006698 EGF receptor Proteins 0.000 description 28
- 108010048367 enhanced green fluorescent protein Proteins 0.000 description 28
- 239000002609 medium Substances 0.000 description 28
- 229960004679 doxorubicin Drugs 0.000 description 26
- 230000000694 effects Effects 0.000 description 25
- 241000699666 Mus <mouse, genus> Species 0.000 description 24
- 108091008146 restriction endonucleases Proteins 0.000 description 23
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 22
- 239000003814 drug Substances 0.000 description 21
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
- 108010079246 OMPA outer membrane proteins Proteins 0.000 description 18
- 229940079593 drug Drugs 0.000 description 18
- 230000005540 biological transmission Effects 0.000 description 17
- 108020004414 DNA Proteins 0.000 description 16
- 102000004142 Trypsin Human genes 0.000 description 15
- 108090000631 Trypsin Proteins 0.000 description 15
- 239000000758 substrate Substances 0.000 description 15
- 239000012588 trypsin Substances 0.000 description 15
- 210000004369 blood Anatomy 0.000 description 14
- 239000008280 blood Substances 0.000 description 14
- 239000000499 gel Substances 0.000 description 14
- 239000000203 mixture Substances 0.000 description 14
- 239000006228 supernatant Substances 0.000 description 14
- 230000009466 transformation Effects 0.000 description 14
- 206010061218 Inflammation Diseases 0.000 description 13
- 230000004054 inflammatory process Effects 0.000 description 13
- 238000000746 purification Methods 0.000 description 13
- 241000196324 Embryophyta Species 0.000 description 12
- 241000192125 Firmicutes Species 0.000 description 12
- 108010052285 Membrane Proteins Proteins 0.000 description 12
- 238000001727 in vivo Methods 0.000 description 12
- 108020004707 nucleic acids Proteins 0.000 description 12
- 102000039446 nucleic acids Human genes 0.000 description 12
- 150000007523 nucleic acids Chemical class 0.000 description 12
- 239000003656 tris buffered saline Substances 0.000 description 12
- 229960002685 biotin Drugs 0.000 description 11
- 235000020958 biotin Nutrition 0.000 description 11
- 239000011616 biotin Substances 0.000 description 11
- 210000004204 blood vessel Anatomy 0.000 description 11
- 238000011161 development Methods 0.000 description 11
- 102000004190 Enzymes Human genes 0.000 description 10
- 108090000790 Enzymes Proteins 0.000 description 10
- 102000018697 Membrane Proteins Human genes 0.000 description 10
- 229940088598 enzyme Drugs 0.000 description 10
- 230000004927 fusion Effects 0.000 description 10
- 239000002502 liposome Substances 0.000 description 10
- 239000000523 sample Substances 0.000 description 10
- 229920001817 Agar Polymers 0.000 description 9
- 241000203069 Archaea Species 0.000 description 9
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
- 239000006142 Luria-Bertani Agar Substances 0.000 description 9
- 239000008272 agar Substances 0.000 description 9
- 230000030833 cell death Effects 0.000 description 9
- 238000001962 electrophoresis Methods 0.000 description 9
- 230000028993 immune response Effects 0.000 description 9
- 238000000338 in vitro Methods 0.000 description 9
- 206010009944 Colon cancer Diseases 0.000 description 8
- 102000004127 Cytokines Human genes 0.000 description 8
- 108090000695 Cytokines Proteins 0.000 description 8
- 108700028353 OmpC Proteins 0.000 description 8
- 108700006385 OmpF Proteins 0.000 description 8
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 8
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 8
- 229940041181 antineoplastic drug Drugs 0.000 description 8
- 239000006059 cover glass Substances 0.000 description 8
- 238000001378 electrochemiluminescence detection Methods 0.000 description 8
- 238000001125 extrusion Methods 0.000 description 8
- 230000006698 induction Effects 0.000 description 8
- 208000027866 inflammatory disease Diseases 0.000 description 8
- 239000000463 material Substances 0.000 description 8
- 210000002966 serum Anatomy 0.000 description 8
- 230000035939 shock Effects 0.000 description 8
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 7
- 101000851176 Homo sapiens Pro-epidermal growth factor Proteins 0.000 description 7
- 239000002033 PVDF binder Substances 0.000 description 7
- 102000003992 Peroxidases Human genes 0.000 description 7
- 229920001213 Polysorbate 20 Polymers 0.000 description 7
- 241000700605 Viruses Species 0.000 description 7
- 238000002474 experimental method Methods 0.000 description 7
- 230000001965 increasing effect Effects 0.000 description 7
- 230000034217 membrane fusion Effects 0.000 description 7
- GVUGOAYIVIDWIO-UFWWTJHBSA-N nepidermin Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)NC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CS)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CS)NC(=O)[C@H](C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C(C)C)C(C)C)C1=CC=C(O)C=C1 GVUGOAYIVIDWIO-UFWWTJHBSA-N 0.000 description 7
- 108040007629 peroxidase activity proteins Proteins 0.000 description 7
- 229920002401 polyacrylamide Polymers 0.000 description 7
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 7
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 7
- 235000020183 skimmed milk Nutrition 0.000 description 7
- 102000004889 Interleukin-6 Human genes 0.000 description 6
- 108090001005 Interleukin-6 Proteins 0.000 description 6
- 108010014251 Muramidase Proteins 0.000 description 6
- 102000016943 Muramidase Human genes 0.000 description 6
- 108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 description 6
- 210000001744 T-lymphocyte Anatomy 0.000 description 6
- 229960000723 ampicillin Drugs 0.000 description 6
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 6
- 230000001413 cellular effect Effects 0.000 description 6
- 238000005119 centrifugation Methods 0.000 description 6
- 208000029742 colonic neoplasm Diseases 0.000 description 6
- 230000008105 immune reaction Effects 0.000 description 6
- 229930027917 kanamycin Natural products 0.000 description 6
- 229960000318 kanamycin Drugs 0.000 description 6
- SBUJHOSQTJFQJX-NOAMYHISSA-N kanamycin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SBUJHOSQTJFQJX-NOAMYHISSA-N 0.000 description 6
- 229930182823 kanamycin A Natural products 0.000 description 6
- 229960000274 lysozyme Drugs 0.000 description 6
- 239000004325 lysozyme Substances 0.000 description 6
- 235000010335 lysozyme Nutrition 0.000 description 6
- 238000013507 mapping Methods 0.000 description 6
- 201000001441 melanoma Diseases 0.000 description 6
- 239000002105 nanoparticle Substances 0.000 description 6
- 229920002981 polyvinylidene fluoride Polymers 0.000 description 6
- 239000011148 porous material Substances 0.000 description 6
- 102000004196 processed proteins & peptides Human genes 0.000 description 6
- 239000012264 purified product Substances 0.000 description 6
- 231100000331 toxic Toxicity 0.000 description 6
- 230000002588 toxic effect Effects 0.000 description 6
- 238000012546 transfer Methods 0.000 description 6
- 208000019553 vascular disease Diseases 0.000 description 6
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 5
- 241000620209 Escherichia coli DH5[alpha] Species 0.000 description 5
- 229930040373 Paraformaldehyde Natural products 0.000 description 5
- 239000002202 Polyethylene glycol Substances 0.000 description 5
- 239000004037 angiogenesis inhibitor Substances 0.000 description 5
- 229940121369 angiogenesis inhibitor Drugs 0.000 description 5
- 239000002260 anti-inflammatory agent Substances 0.000 description 5
- 229940121363 anti-inflammatory agent Drugs 0.000 description 5
- 230000008901 benefit Effects 0.000 description 5
- 230000027455 binding Effects 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- JVXZRNYCRFIEGV-UHFFFAOYSA-M dilC18(3) dye Chemical compound [O-]Cl(=O)(=O)=O.CC1(C)C2=CC=CC=C2N(CCCCCCCCCCCCCCCCCC)C1=CC=CC1=[N+](CCCCCCCCCCCCCCCCCC)C2=CC=CC=C2C1(C)C JVXZRNYCRFIEGV-UHFFFAOYSA-M 0.000 description 5
- 238000012377 drug delivery Methods 0.000 description 5
- 238000004520 electroporation Methods 0.000 description 5
- 238000011534 incubation Methods 0.000 description 5
- 150000002632 lipids Chemical class 0.000 description 5
- 229920002866 paraformaldehyde Polymers 0.000 description 5
- 229920001223 polyethylene glycol Polymers 0.000 description 5
- 238000006116 polymerization reaction Methods 0.000 description 5
- 230000028327 secretion Effects 0.000 description 5
- 239000003053 toxin Substances 0.000 description 5
- 231100000765 toxin Toxicity 0.000 description 5
- 108700012359 toxins Proteins 0.000 description 5
- 210000003556 vascular endothelial cell Anatomy 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 235000014469 Bacillus subtilis Nutrition 0.000 description 4
- 229920000858 Cyclodextrin Polymers 0.000 description 4
- UQSXHKLRYXJYBZ-UHFFFAOYSA-N Iron oxide Chemical compound [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 description 4
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 4
- 108091008874 T cell receptors Proteins 0.000 description 4
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 4
- 239000013504 Triton X-100 Substances 0.000 description 4
- 229920004890 Triton X-100 Polymers 0.000 description 4
- 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 4
- 239000011324 bead Substances 0.000 description 4
- 238000012790 confirmation Methods 0.000 description 4
- 239000003102 growth factor Substances 0.000 description 4
- 239000000411 inducer Substances 0.000 description 4
- 230000028709 inflammatory response Effects 0.000 description 4
- BPHPUYQFMNQIOC-NXRLNHOXSA-N isopropyl beta-D-thiogalactopyranoside Chemical compound CC(C)S[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O BPHPUYQFMNQIOC-NXRLNHOXSA-N 0.000 description 4
- 201000005202 lung cancer Diseases 0.000 description 4
- 208000020816 lung neoplasm Diseases 0.000 description 4
- 210000002540 macrophage Anatomy 0.000 description 4
- 210000003071 memory t lymphocyte Anatomy 0.000 description 4
- 239000011859 microparticle Substances 0.000 description 4
- 231100000957 no side effect Toxicity 0.000 description 4
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 4
- UQDJGEHQDNVPGU-UHFFFAOYSA-N serine phosphoethanolamine Chemical compound [NH3+]CCOP([O-])(=O)OCC([NH3+])C([O-])=O UQDJGEHQDNVPGU-UHFFFAOYSA-N 0.000 description 4
- 239000012679 serum free medium Substances 0.000 description 4
- 230000011664 signaling Effects 0.000 description 4
- 230000008685 targeting Effects 0.000 description 4
- 210000005167 vascular cell Anatomy 0.000 description 4
- 108010071023 Bacterial Outer Membrane Proteins Proteins 0.000 description 3
- 206010006187 Breast cancer Diseases 0.000 description 3
- 208000026310 Breast neoplasm Diseases 0.000 description 3
- 241000672609 Escherichia coli BL21 Species 0.000 description 3
- 241000233866 Fungi Species 0.000 description 3
- 108010064593 Intercellular Adhesion Molecule-1 Proteins 0.000 description 3
- 102000015271 Intercellular Adhesion Molecule-1 Human genes 0.000 description 3
- 102100037850 Interferon gamma Human genes 0.000 description 3
- 108010074328 Interferon-gamma Proteins 0.000 description 3
- 108090000174 Interleukin-10 Proteins 0.000 description 3
- 102000013691 Interleukin-17 Human genes 0.000 description 3
- 108050003558 Interleukin-17 Proteins 0.000 description 3
- 108090000978 Interleukin-4 Proteins 0.000 description 3
- 102000004388 Interleukin-4 Human genes 0.000 description 3
- 239000000232 Lipid Bilayer Substances 0.000 description 3
- 108010064548 Lymphocyte Function-Associated Antigen-1 Proteins 0.000 description 3
- 206010027476 Metastases Diseases 0.000 description 3
- MSFSPUZXLOGKHJ-UHFFFAOYSA-N Muraminsaeure Natural products OC(=O)C(C)OC1C(N)C(O)OC(CO)C1O MSFSPUZXLOGKHJ-UHFFFAOYSA-N 0.000 description 3
- 229930012538 Paclitaxel Natural products 0.000 description 3
- 208000002193 Pain Diseases 0.000 description 3
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 3
- 108091093037 Peptide nucleic acid Proteins 0.000 description 3
- 108010013639 Peptidoglycan Proteins 0.000 description 3
- 206010039491 Sarcoma Diseases 0.000 description 3
- 206010040047 Sepsis Diseases 0.000 description 3
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 3
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 3
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 3
- 210000000683 abdominal cavity Anatomy 0.000 description 3
- 239000011543 agarose gel Substances 0.000 description 3
- 230000000692 anti-sense effect Effects 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 239000003636 conditioned culture medium Substances 0.000 description 3
- 239000000470 constituent Substances 0.000 description 3
- 238000012258 culturing Methods 0.000 description 3
- 230000034994 death Effects 0.000 description 3
- 238000000354 decomposition reaction Methods 0.000 description 3
- 229960002593 desoximetasone Drugs 0.000 description 3
- VWVSBHGCDBMOOT-IIEHVVJPSA-N desoximetasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@H](C(=O)CO)[C@@]1(C)C[C@@H]2O VWVSBHGCDBMOOT-IIEHVVJPSA-N 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 238000010586 diagram Methods 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 239000002158 endotoxin Substances 0.000 description 3
- 239000001963 growth medium Substances 0.000 description 3
- 230000016784 immunoglobulin production Effects 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 230000002458 infectious effect Effects 0.000 description 3
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 3
- 230000009401 metastasis Effects 0.000 description 3
- 210000005087 mononuclear cell Anatomy 0.000 description 3
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 3
- 229960001592 paclitaxel Drugs 0.000 description 3
- 201000002528 pancreatic cancer Diseases 0.000 description 3
- 208000008443 pancreatic carcinoma Diseases 0.000 description 3
- 239000012188 paraffin wax Substances 0.000 description 3
- 239000002096 quantum dot Substances 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 230000009885 systemic effect Effects 0.000 description 3
- 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 3
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 3
- OSBLTNPMIGYQGY-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;2-[2-[bis(carboxymethyl)amino]ethyl-(carboxymethyl)amino]acetic acid;boric acid Chemical compound OB(O)O.OCC(N)(CO)CO.OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O OSBLTNPMIGYQGY-UHFFFAOYSA-N 0.000 description 2
- 108020005544 Antisense RNA Proteins 0.000 description 2
- 108091023037 Aptamer Proteins 0.000 description 2
- 206010003210 Arteriosclerosis Diseases 0.000 description 2
- 244000063299 Bacillus subtilis Species 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 108010022366 Carcinoembryonic Antigen Proteins 0.000 description 2
- 102100025475 Carcinoembryonic antigen-related cell adhesion molecule 5 Human genes 0.000 description 2
- 201000009030 Carcinoma Diseases 0.000 description 2
- DLGOEMSEDOSKAD-UHFFFAOYSA-N Carmustine Chemical compound ClCCNC(=O)N(N=O)CCCl DLGOEMSEDOSKAD-UHFFFAOYSA-N 0.000 description 2
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 2
- 108010092160 Dactinomycin Proteins 0.000 description 2
- 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 2
- 108050007372 Fibroblast Growth Factor Proteins 0.000 description 2
- 102000018233 Fibroblast Growth Factor Human genes 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- 206010018364 Glomerulonephritis Diseases 0.000 description 2
- 241000711549 Hepacivirus C Species 0.000 description 2
- 241000700721 Hepatitis B virus Species 0.000 description 2
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 2
- 241000725303 Human immunodeficiency virus Species 0.000 description 2
- 238000012404 In vitro experiment Methods 0.000 description 2
- 108010050904 Interferons Proteins 0.000 description 2
- 102000014150 Interferons Human genes 0.000 description 2
- 102000015696 Interleukins Human genes 0.000 description 2
- 108010063738 Interleukins Proteins 0.000 description 2
- 108090001030 Lipoproteins Proteins 0.000 description 2
- 102000004895 Lipoproteins Human genes 0.000 description 2
- GQYIWUVLTXOXAJ-UHFFFAOYSA-N Lomustine Chemical compound ClCCN(N=O)C(=O)NC1CCCCC1 GQYIWUVLTXOXAJ-UHFFFAOYSA-N 0.000 description 2
- 208000021642 Muscular disease Diseases 0.000 description 2
- 201000009623 Myopathy Diseases 0.000 description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
- 241000589517 Pseudomonas aeruginosa Species 0.000 description 2
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 2
- 108020004459 Small interfering RNA Proteins 0.000 description 2
- 241000191967 Staphylococcus aureus Species 0.000 description 2
- 239000008051 TBE buffer Substances 0.000 description 2
- 238000003917 TEM image Methods 0.000 description 2
- 108010000134 Vascular Cell Adhesion Molecule-1 Proteins 0.000 description 2
- 102100023543 Vascular cell adhesion protein 1 Human genes 0.000 description 2
- 201000004810 Vascular dementia Diseases 0.000 description 2
- 206010047115 Vasculitis Diseases 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 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 2
- 230000009471 action Effects 0.000 description 2
- 235000001014 amino acid Nutrition 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 230000001093 anti-cancer Effects 0.000 description 2
- 230000000890 antigenic effect Effects 0.000 description 2
- 208000011775 arteriosclerosis disease Diseases 0.000 description 2
- 208000006673 asthma Diseases 0.000 description 2
- 230000005907 cancer growth Effects 0.000 description 2
- 229960004562 carboplatin Drugs 0.000 description 2
- 190000008236 carboplatin Chemical compound 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 2
- 229960004316 cisplatin Drugs 0.000 description 2
- 210000001072 colon Anatomy 0.000 description 2
- 239000003184 complementary RNA Substances 0.000 description 2
- 230000001086 cytosolic effect Effects 0.000 description 2
- 229960000640 dactinomycin Drugs 0.000 description 2
- 238000002405 diagnostic procedure Methods 0.000 description 2
- 238000000502 dialysis Methods 0.000 description 2
- 238000007865 diluting Methods 0.000 description 2
- 229940115080 doxil Drugs 0.000 description 2
- 210000003743 erythrocyte Anatomy 0.000 description 2
- 229940126864 fibroblast growth factor Drugs 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 108091006047 fluorescent proteins Proteins 0.000 description 2
- 102000034287 fluorescent proteins Human genes 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 208000035474 group of disease Diseases 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 2
- 238000006703 hydration reaction Methods 0.000 description 2
- 210000002865 immune cell Anatomy 0.000 description 2
- 238000003364 immunohistochemistry Methods 0.000 description 2
- 239000002955 immunomodulating agent Substances 0.000 description 2
- 229940121354 immunomodulator Drugs 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
- 230000002757 inflammatory effect Effects 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 229940079322 interferon Drugs 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 208000017169 kidney disease Diseases 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 230000002503 metabolic effect Effects 0.000 description 2
- 108091070501 miRNA Proteins 0.000 description 2
- 239000002679 microRNA Substances 0.000 description 2
- 238000001000 micrograph Methods 0.000 description 2
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 210000003200 peritoneal cavity Anatomy 0.000 description 2
- 230000026731 phosphorylation Effects 0.000 description 2
- 238000006366 phosphorylation reaction Methods 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 239000000941 radioactive substance Substances 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- PYWVYCXTNDRMGF-UHFFFAOYSA-N rhodamine B Chemical compound [Cl-].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=CC=C1C(O)=O PYWVYCXTNDRMGF-UHFFFAOYSA-N 0.000 description 2
- 239000002924 silencing RNA Substances 0.000 description 2
- 239000001509 sodium citrate Substances 0.000 description 2
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 2
- 238000000527 sonication Methods 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 230000001131 transforming effect Effects 0.000 description 2
- 238000005199 ultracentrifugation Methods 0.000 description 2
- 241000712461 unidentified influenza virus Species 0.000 description 2
- 230000024883 vasodilation Effects 0.000 description 2
- 229960004528 vincristine Drugs 0.000 description 2
- 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 2
- 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 2
- 239000008096 xylene Substances 0.000 description 2
- VEEGZPWAAPPXRB-BJMVGYQFSA-N (3e)-3-(1h-imidazol-5-ylmethylidene)-1h-indol-2-one Chemical compound O=C1NC2=CC=CC=C2\C1=C/C1=CN=CN1 VEEGZPWAAPPXRB-BJMVGYQFSA-N 0.000 description 1
- MWWSFMDVAYGXBV-MYPASOLCSA-N (7r,9s)-7-[(2r,4s,5s,6s)-4-amino-5-hydroxy-6-methyloxan-2-yl]oxy-6,9,11-trihydroxy-9-(2-hydroxyacetyl)-4-methoxy-8,10-dihydro-7h-tetracene-5,12-dione;hydrochloride Chemical compound Cl.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 MWWSFMDVAYGXBV-MYPASOLCSA-N 0.000 description 1
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- DJQYYYCQOZMCRC-UHFFFAOYSA-N 2-aminopropane-1,3-dithiol Chemical group SCC(N)CS DJQYYYCQOZMCRC-UHFFFAOYSA-N 0.000 description 1
- VADKRMSMGWJZCF-UHFFFAOYSA-N 2-bromophenol Chemical compound OC1=CC=CC=C1Br VADKRMSMGWJZCF-UHFFFAOYSA-N 0.000 description 1
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 1
- STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 208000003343 Antiphospholipid Syndrome Diseases 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 208000009137 Behcet syndrome Diseases 0.000 description 1
- 108010006654 Bleomycin Proteins 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 208000014644 Brain disease Diseases 0.000 description 1
- 244000056139 Brassica cretica Species 0.000 description 1
- 235000003351 Brassica cretica Nutrition 0.000 description 1
- 235000003343 Brassica rupestris Nutrition 0.000 description 1
- 206010006448 Bronchiolitis Diseases 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- 101100289995 Caenorhabditis elegans mac-1 gene Proteins 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 108010067225 Cell Adhesion Molecules Proteins 0.000 description 1
- 102000016289 Cell Adhesion Molecules Human genes 0.000 description 1
- 108010059892 Cellulase Proteins 0.000 description 1
- 206010008342 Cervix carcinoma Diseases 0.000 description 1
- 229920002101 Chitin Polymers 0.000 description 1
- 108010022172 Chitinases Proteins 0.000 description 1
- 102000012286 Chitinases Human genes 0.000 description 1
- 102000009016 Cholera Toxin Human genes 0.000 description 1
- 108010049048 Cholera Toxin Proteins 0.000 description 1
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 1
- 108020004705 Codon Proteins 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
- 239000012624 DNA alkylating agent Substances 0.000 description 1
- 229940126161 DNA alkylating agent Drugs 0.000 description 1
- 230000004543 DNA replication Effects 0.000 description 1
- 206010012438 Dermatitis atopic Diseases 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 208000005189 Embolism Diseases 0.000 description 1
- 206010014561 Emphysema Diseases 0.000 description 1
- 101710121765 Endo-1,4-beta-xylanase Proteins 0.000 description 1
- 208000004145 Endometritis Diseases 0.000 description 1
- 241000588697 Enterobacter cloacae Species 0.000 description 1
- 241000194032 Enterococcus faecalis Species 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 229920001917 Ficoll Polymers 0.000 description 1
- WJOHZNCJWYWUJD-IUGZLZTKSA-N Fluocinonide Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)COC(=O)C)[C@@]2(C)C[C@@H]1O WJOHZNCJWYWUJD-IUGZLZTKSA-N 0.000 description 1
- 208000022072 Gallbladder Neoplasms Diseases 0.000 description 1
- 208000007882 Gastritis Diseases 0.000 description 1
- 208000017189 Gastrointestinal inflammatory disease Diseases 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 108010043121 Green Fluorescent Proteins Proteins 0.000 description 1
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 description 1
- 206010020565 Hyperaemia Diseases 0.000 description 1
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 1
- XDXDZDZNSLXDNA-TZNDIEGXSA-N Idarubicin Chemical compound C1[C@H](N)[C@H](O)[C@H](C)O[C@H]1O[C@@H]1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2C[C@@](O)(C(C)=O)C1 XDXDZDZNSLXDNA-TZNDIEGXSA-N 0.000 description 1
- XDXDZDZNSLXDNA-UHFFFAOYSA-N Idarubicin Natural products C1C(N)C(O)C(C)OC1OC1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2CC(O)(C(C)=O)C1 XDXDZDZNSLXDNA-UHFFFAOYSA-N 0.000 description 1
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 1
- 102000005755 Intercellular Signaling Peptides and Proteins Human genes 0.000 description 1
- 108010070716 Intercellular Signaling Peptides and Proteins Proteins 0.000 description 1
- 102000013462 Interleukin-12 Human genes 0.000 description 1
- 108010065805 Interleukin-12 Proteins 0.000 description 1
- 108010002350 Interleukin-2 Proteins 0.000 description 1
- 102000000588 Interleukin-2 Human genes 0.000 description 1
- 208000008839 Kidney Neoplasms Diseases 0.000 description 1
- 241000588915 Klebsiella aerogenes Species 0.000 description 1
- 201000008225 Klebsiella pneumonia Diseases 0.000 description 1
- 241000588747 Klebsiella pneumoniae Species 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- 206010023825 Laryngeal cancer Diseases 0.000 description 1
- 201000008197 Laryngitis Diseases 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- 108010030317 Macrophage-1 Antigen Proteins 0.000 description 1
- 239000005913 Maltodextrin Substances 0.000 description 1
- 229920002774 Maltodextrin Polymers 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 229930192392 Mitomycin Natural products 0.000 description 1
- 208000034578 Multiple myelomas Diseases 0.000 description 1
- 101000851196 Mus musculus Pro-epidermal growth factor Proteins 0.000 description 1
- 208000009525 Myocarditis Diseases 0.000 description 1
- 201000004458 Myoma Diseases 0.000 description 1
- 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 1
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 206010030216 Oesophagitis Diseases 0.000 description 1
- 206010033078 Otitis media Diseases 0.000 description 1
- 101710116435 Outer membrane protein Proteins 0.000 description 1
- 206010033645 Pancreatitis Diseases 0.000 description 1
- 208000008469 Peptic Ulcer Diseases 0.000 description 1
- 229940122907 Phosphatase inhibitor Drugs 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 102100024616 Platelet endothelial cell adhesion molecule Human genes 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- 206010035717 Pneumonia klebsiella Diseases 0.000 description 1
- 108010059820 Polygalacturonase Proteins 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 238000012228 RNA interference-mediated gene silencing Methods 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 208000015634 Rectal Neoplasms Diseases 0.000 description 1
- 206010038389 Renal cancer Diseases 0.000 description 1
- 241000831652 Salinivibrio sharmensis Species 0.000 description 1
- 101100021843 Shigella flexneri lpxM1 gene Proteins 0.000 description 1
- 101100021844 Shigella flexneri lpxM2 gene Proteins 0.000 description 1
- 208000021386 Sjogren Syndrome Diseases 0.000 description 1
- 208000000453 Skin Neoplasms Diseases 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 208000006045 Spondylarthropathies Diseases 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- ZSJLQEPLLKMAKR-UHFFFAOYSA-N Streptozotocin Natural products O=NN(C)C(=O)NC1C(O)OC(CO)C(O)C1O ZSJLQEPLLKMAKR-UHFFFAOYSA-N 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 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 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 201000009594 Systemic Scleroderma Diseases 0.000 description 1
- 206010042953 Systemic sclerosis Diseases 0.000 description 1
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 description 1
- FOCVUCIESVLUNU-UHFFFAOYSA-N Thiotepa Chemical compound C1CN1P(N1CC1)(=S)N1CC1 FOCVUCIESVLUNU-UHFFFAOYSA-N 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- COQLPRJCUIATTQ-UHFFFAOYSA-N Uranyl acetate Chemical compound O.O.O=[U]=O.CC(O)=O.CC(O)=O COQLPRJCUIATTQ-UHFFFAOYSA-N 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- 206010046914 Vaginal infection Diseases 0.000 description 1
- 201000008100 Vaginitis Diseases 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
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 206010000891 acute myocardial infarction Diseases 0.000 description 1
- 206010001053 acute respiratory failure Diseases 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 229930013930 alkaloid Natural products 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- 229940037003 alum Drugs 0.000 description 1
- 229960003099 amcinonide Drugs 0.000 description 1
- ILKJAFIWWBXGDU-MOGDOJJUSA-N amcinonide Chemical compound O([C@@]1([C@H](O2)C[C@@H]3[C@@]1(C[C@H](O)[C@]1(F)[C@@]4(C)C=CC(=O)C=C4CC[C@H]13)C)C(=O)COC(=O)C)C12CCCC1 ILKJAFIWWBXGDU-MOGDOJJUSA-N 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 230000005875 antibody response Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical class CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 1
- 201000008937 atopic dermatitis Diseases 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 239000003012 bilayer membrane Substances 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 238000010170 biological method Methods 0.000 description 1
- QKSKPIVNLNLAAV-UHFFFAOYSA-N bis(2-chloroethyl) sulfide Chemical compound ClCCSCCCl QKSKPIVNLNLAAV-UHFFFAOYSA-N 0.000 description 1
- 229960001561 bleomycin Drugs 0.000 description 1
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- UDSAIICHUKSCKT-UHFFFAOYSA-N bromophenol blue Chemical compound C1=C(Br)C(O)=C(Br)C=C1C1(C=2C=C(Br)C(O)=C(Br)C=2)C2=CC=CC=C2S(=O)(=O)O1 UDSAIICHUKSCKT-UHFFFAOYSA-N 0.000 description 1
- 201000009267 bronchiectasis Diseases 0.000 description 1
- 206010006451 bronchitis Diseases 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 239000007975 buffered saline Substances 0.000 description 1
- 229960002092 busulfan Drugs 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 230000004611 cancer cell death Effects 0.000 description 1
- 229940022399 cancer vaccine Drugs 0.000 description 1
- 238000009566 cancer vaccine Methods 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000002041 carbon nanotube Substances 0.000 description 1
- 229910021393 carbon nanotube Inorganic materials 0.000 description 1
- 229960005243 carmustine Drugs 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000022534 cell killing Effects 0.000 description 1
- 230000006037 cell lysis Effects 0.000 description 1
- 230000010307 cell transformation Effects 0.000 description 1
- 229940106157 cellulase Drugs 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000000919 ceramic Substances 0.000 description 1
- 201000010881 cervical cancer Diseases 0.000 description 1
- JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 description 1
- 229960004630 chlorambucil Drugs 0.000 description 1
- 208000003167 cholangitis Diseases 0.000 description 1
- 201000001352 cholecystitis Diseases 0.000 description 1
- 208000037976 chronic inflammation Diseases 0.000 description 1
- 230000006020 chronic inflammation Effects 0.000 description 1
- 229960004703 clobetasol propionate Drugs 0.000 description 1
- CBGUOGMQLZIXBE-XGQKBEPLSA-N clobetasol propionate Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)CCl)(OC(=O)CC)[C@@]1(C)C[C@@H]2O CBGUOGMQLZIXBE-XGQKBEPLSA-N 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 210000001608 connective tissue cell Anatomy 0.000 description 1
- 239000002872 contrast media Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 229960004397 cyclophosphamide Drugs 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 1
- 229960000975 daunorubicin Drugs 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000003412 degenerative effect Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 210000004443 dendritic cell Anatomy 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 229960003957 dexamethasone Drugs 0.000 description 1
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 239000000032 diagnostic agent Substances 0.000 description 1
- 229940039227 diagnostic agent Drugs 0.000 description 1
- 229960001259 diclofenac Drugs 0.000 description 1
- DCOPUUMXTXDBNB-UHFFFAOYSA-N diclofenac Chemical compound OC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl DCOPUUMXTXDBNB-UHFFFAOYSA-N 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 229960002124 diflorasone diacetate Drugs 0.000 description 1
- BOBLHFUVNSFZPJ-JOYXJVLSSA-N diflorasone diacetate Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@H](C)[C@@](C(=O)COC(C)=O)(OC(C)=O)[C@@]2(C)C[C@@H]1O BOBLHFUVNSFZPJ-JOYXJVLSSA-N 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 208000009190 disseminated intravascular coagulation Diseases 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 229960003668 docetaxel Drugs 0.000 description 1
- 238000002296 dynamic light scattering Methods 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 206010014665 endocarditis Diseases 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 229940092559 enterobacter aerogenes Drugs 0.000 description 1
- 229940032049 enterococcus faecalis Drugs 0.000 description 1
- 230000001667 episodic effect Effects 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 208000006881 esophagitis Diseases 0.000 description 1
- VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 description 1
- 229960005420 etoposide Drugs 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 108010093305 exopolygalacturonase Proteins 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- 230000035558 fertility Effects 0.000 description 1
- 229960000785 fluocinonide Drugs 0.000 description 1
- 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 1
- 238000001997 free-flow electrophoresis Methods 0.000 description 1
- 201000010175 gallbladder cancer Diseases 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 238000002523 gelfiltration Methods 0.000 description 1
- 230000009368 gene silencing by RNA Effects 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 229940022353 herceptin Drugs 0.000 description 1
- 238000000265 homogenisation Methods 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 229960001680 ibuprofen Drugs 0.000 description 1
- 229960000908 idarubicin Drugs 0.000 description 1
- HOMGKSMUEGBAAB-UHFFFAOYSA-N ifosfamide Chemical compound ClCCNP1(=O)OCCCN1CCCl HOMGKSMUEGBAAB-UHFFFAOYSA-N 0.000 description 1
- 229960001101 ifosfamide Drugs 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 229960003444 immunosuppressant agent Drugs 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 229960000905 indomethacin Drugs 0.000 description 1
- 210000004969 inflammatory cell Anatomy 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 108010044426 integrins Proteins 0.000 description 1
- 102000006495 integrins Human genes 0.000 description 1
- 230000031146 intracellular signal transduction Effects 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 208000002551 irritable bowel syndrome Diseases 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 201000010982 kidney cancer Diseases 0.000 description 1
- 210000002429 large intestine Anatomy 0.000 description 1
- 206010023841 laryngeal neoplasm Diseases 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 229920006008 lipopolysaccharide Polymers 0.000 description 1
- 206010024627 liposarcoma Diseases 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 201000007270 liver cancer Diseases 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 229960002247 lomustine Drugs 0.000 description 1
- 101150060640 lpxM gene Proteins 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 239000006249 magnetic particle Substances 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 229940035034 maltodextrin Drugs 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 238000010297 mechanical methods and process Methods 0.000 description 1
- HAWPXGHAZFHHAD-UHFFFAOYSA-N mechlorethamine Chemical compound ClCCN(C)CCCl HAWPXGHAZFHHAD-UHFFFAOYSA-N 0.000 description 1
- 229960004961 mechlorethamine Drugs 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 229940115256 melanoma vaccine Drugs 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 238000000520 microinjection Methods 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- CFCUWKMKBJTWLW-BKHRDMLASA-N mithramycin Chemical compound O([C@@H]1C[C@@H](O[C@H](C)[C@H]1O)OC=1C=C2C=C3C[C@H]([C@@H](C(=O)C3=C(O)C2=C(O)C=1C)O[C@@H]1O[C@H](C)[C@@H](O)[C@H](O[C@@H]2O[C@H](C)[C@H](O)[C@H](O[C@@H]3O[C@H](C)[C@@H](O)[C@@](C)(O)C3)C2)C1)[C@H](OC)C(=O)[C@@H](O)[C@@H](C)O)[C@H]1C[C@@H](O)[C@H](O)[C@@H](C)O1 CFCUWKMKBJTWLW-BKHRDMLASA-N 0.000 description 1
- 229960004857 mitomycin Drugs 0.000 description 1
- 229960001156 mitoxantrone Drugs 0.000 description 1
- KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 229960002744 mometasone furoate Drugs 0.000 description 1
- WOFMFGQZHJDGCX-ZULDAHANSA-N mometasone furoate Chemical compound O([C@]1([C@@]2(C)C[C@H](O)[C@]3(Cl)[C@@]4(C)C=CC(=O)C=C4CC[C@H]3[C@@H]2C[C@H]1C)C(=O)CCl)C(=O)C1=CC=CO1 WOFMFGQZHJDGCX-ZULDAHANSA-N 0.000 description 1
- 235000010460 mustard Nutrition 0.000 description 1
- 201000009240 nasopharyngitis Diseases 0.000 description 1
- 210000000944 nerve tissue Anatomy 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- 201000008968 osteosarcoma Diseases 0.000 description 1
- 230000007310 pathophysiology Effects 0.000 description 1
- 208000011906 peptic ulcer disease Diseases 0.000 description 1
- 208000008494 pericarditis Diseases 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 229960005190 phenylalanine Drugs 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229960002702 piroxicam Drugs 0.000 description 1
- QYSPLQLAKJAUJT-UHFFFAOYSA-N piroxicam Chemical compound OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=CC=CC=N1 QYSPLQLAKJAUJT-UHFFFAOYSA-N 0.000 description 1
- 238000003976 plant breeding Methods 0.000 description 1
- 230000004260 plant-type cell wall biogenesis Effects 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229960003171 plicamycin Drugs 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 238000003752 polymerase chain reaction Methods 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 229960004618 prednisone Drugs 0.000 description 1
- XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 1
- 230000004853 protein function Effects 0.000 description 1
- 208000005069 pulmonary fibrosis Diseases 0.000 description 1
- 239000002510 pyrogen Substances 0.000 description 1
- 206010038038 rectal cancer Diseases 0.000 description 1
- 201000001275 rectum cancer Diseases 0.000 description 1
- 201000004193 respiratory failure Diseases 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 206010039083 rhinitis Diseases 0.000 description 1
- 229960004641 rituximab Drugs 0.000 description 1
- 201000000980 schizophrenia Diseases 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000008054 signal transmission Effects 0.000 description 1
- 238000009097 single-agent therapy Methods 0.000 description 1
- 201000009890 sinusitis Diseases 0.000 description 1
- 201000000849 skin cancer Diseases 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- -1 solmedrol Chemical compound 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 201000005671 spondyloarthropathy Diseases 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 201000011549 stomach cancer Diseases 0.000 description 1
- 229960001052 streptozocin Drugs 0.000 description 1
- ZSJLQEPLLKMAKR-GKHCUFPYSA-N streptozocin Chemical compound O=NN(C)C(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O ZSJLQEPLLKMAKR-GKHCUFPYSA-N 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- NRUKOCRGYNPUPR-QBPJDGROSA-N teniposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@@H](OC[C@H]4O3)C=3SC=CC=3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 NRUKOCRGYNPUPR-QBPJDGROSA-N 0.000 description 1
- 229960001278 teniposide Drugs 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 229960001196 thiotepa Drugs 0.000 description 1
- 206010043778 thyroiditis Diseases 0.000 description 1
- 230000008467 tissue growth Effects 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 229960000303 topotecan Drugs 0.000 description 1
- UCFGDBYHRUNTLO-QHCPKHFHSA-N topotecan Chemical compound C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 UCFGDBYHRUNTLO-QHCPKHFHSA-N 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- 230000000472 traumatic effect Effects 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 229950008396 ulobetasol propionate Drugs 0.000 description 1
- BDSYKGHYMJNPAB-LICBFIPMSA-N ulobetasol propionate Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@H](C)[C@@](C(=O)CCl)(OC(=O)CC)[C@@]2(C)C[C@@H]1O BDSYKGHYMJNPAB-LICBFIPMSA-N 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
- 238000002255 vaccination Methods 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 238000009423 ventilation Methods 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
- 238000005303 weighing Methods 0.000 description 1
- 239000012130 whole-cell lysate Substances 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/66—Microorganisms or materials therefrom
-
- 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
- A61K38/162—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from virus
-
- 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
- A61K38/18—Growth factors; Growth regulators
- A61K38/1825—Fibroblast growth factor [FGF]
-
- 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
- A61K38/18—Growth factors; Growth regulators
- A61K38/1858—Platelet-derived growth factor [PDGF]
- A61K38/1866—Vascular endothelial growth factor [VEGF]
-
- 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
- A61K38/19—Cytokines; Lymphokines; Interferons
- A61K38/20—Interleukins [IL]
-
- 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
- A61K38/19—Cytokines; Lymphokines; Interferons
- A61K38/21—Interferons [IFN]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/0005—Vertebrate antigens
- A61K39/0011—Cancer antigens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/02—Bacterial antigens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/39—Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/40—Cyclodextrins; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/46—Ingredients of undetermined constitution or reaction products thereof, e.g. skin, bone, milk, cotton fibre, eggshell, oxgall or plant extracts
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/69—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
- A61K47/6905—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a colloid or an emulsion
- A61K47/6917—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a colloid or an emulsion the form being a lipoprotein vesicle, e.g. HDL or LDL proteins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/001—Preparation for luminescence or biological staining
- A61K49/0013—Luminescence
- A61K49/0017—Fluorescence in vivo
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/001—Preparation for luminescence or biological staining
- A61K49/0013—Luminescence
- A61K49/0017—Fluorescence in vivo
- A61K49/0019—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules
- A61K49/0045—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules the fluorescent agent being a peptide or protein used for imaging or diagnosis in vivo
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/001—Preparation for luminescence or biological staining
- A61K49/0063—Preparation for luminescence or biological staining characterised by a special physical or galenical form, e.g. emulsions, microspheres
- A61K49/0069—Preparation for luminescence or biological staining characterised by a special physical or galenical form, e.g. emulsions, microspheres the agent being in a particular physical galenical form
- A61K49/0097—Cells, viruses, ghosts, red blood cells, viral vectors, used for imaging or diagnosis in vivo
-
- 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—Liposomes
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5063—Compounds of unknown constitution, e.g. material from plants or animals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/71—Receptors; Cell surface antigens; Cell surface determinants for growth factors; for growth regulators
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/87—Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
- C12N15/88—Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation using microencapsulation, e.g. using amphiphile liposome vesicle
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
- A61K2039/55511—Organic adjuvants
- A61K2039/55555—Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S977/00—Nanotechnology
- Y10S977/70—Nanostructure
- Y10S977/773—Nanoparticle, i.e. structure having three dimensions of 100 nm or less
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Organic Chemistry (AREA)
- Biomedical Technology (AREA)
- Microbiology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Mycology (AREA)
- Genetics & Genomics (AREA)
- Virology (AREA)
- Oncology (AREA)
- Dispersion Chemistry (AREA)
- Molecular Biology (AREA)
- Botany (AREA)
- Pathology (AREA)
- Radiology & Medical Imaging (AREA)
- Biotechnology (AREA)
- Wood Science & Technology (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- Biophysics (AREA)
- Hematology (AREA)
- Inorganic Chemistry (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Vascular Medicine (AREA)
Description
一つ目、治療、診断及び/又はワクチンのための多様な物質を既にロードした細胞からマイクロベシクルを製造する。例えば、治療及び診断のための多様な物質を培養液に含ませて細胞を培養すると、前記物質がロードされた細胞を収得することもでき、或いはエレクトロポレーション法で細胞に物質をロードすることもできる。このような細胞から得た原形質体から自然に分泌される、或いは超音波分解、押出、機械的分解などの方法で製造したマイクロベシクルには、前記物質がロードされている。
図1はグラム陰性菌からリゾチーム処理によって原形質体を作った後、原形質体に由来するマイクロベシクルに薬物をロードする方法を示す模式図である。
図1に示した模式図において、押出法と密度勾配法を用いて原形質体由来マイクロベシクルを製造した。
実施例1及び実施例2の方法によって、グラム陰性菌としての大腸菌(E.coli)及びグラム陽性菌としての枯草菌(B.subtilis)の原形質体に由来するマイクロベシクルを製造し、それぞれの特性を分析した。
実施例1及び実施例2の方法によって、グラム陰性菌としての大腸菌(E.coli)及びグラム陽性菌としてのブドウ球菌(S.aureus)の原形質体に由来するマイクロベシクルを製造した。また、グラム陰性菌由来マイクロベシクル[Proteomics. 2007 Sep; 7(17):3143-53.]とグラム陽性菌由来マイクロベシクル[Proteomics. 2009 Dec;9(24):5425-36.]を既存の公知の方法によって得た。
実施例1及び実施例2の方法によって、グラム陰性菌としての大腸菌(E.coli)の原形質体に由来するマイクロベシクルを製造した。また、グラム陰性菌由来マイクロベシクルを得た。
pMSCVベクター(vector)にEGFP遺伝子が融合されたpMSCV−EGFPプラスミド(plasmid)を含むDH5α大腸菌と、前記プラスミドを含まない大腸菌を培養して実施例1及び2と同様の方法で原形質体由来マイクロベシクルを製造した。製造された原形質体マイクロベシクルを鋳型としてEGFPプライマー(primer)を用いてPCR重合反応(polymerase chain reaction)を行った後、DNAをアガロースゲル(TBE緩衝溶液、1%)電気泳動法で確認して図11に示した。使用したEGFPプライマーは次のとおりである。
細菌の原形質体由来マイクロベシクルが細菌にプラスミドを伝達して形質転換させることが可能な能力を有するかを確認するために、次の実験を行った。まず、緑色蛍光を帯びる細菌を作るためにEGFPを発現するプラスミドを製作するために、EGFPの公知のDNA塩基配列に基づいて特定の制限酵素を人為的に挿入して次のとおりプライマーを製作した。
(下線は制限酵素NdeIとSalIの認識配列を意味する)
細菌原形質体由来マイクロベシクルが抗原の運搬体として使用されて抗体生成を誘導するかを調べるために、下記の実験を行った。マイクロベシクルにより抗体生成が誘導されるかを調べるために、単一タンパク質自体では抗体生成誘導を行うことができないタンパク質としてのEGFPタンパク質を用いて、マイクロベシクルがEGFP抗体を形成させることができるかを確認した。
細菌の外膜タンパク質の一つであるOmpAは、人為的に過発現させる場合、細菌内に存在する封入体(inclusion body)に存在する。そのため、人為的に過発現したOmpAタンパク質を確認する場合、マイクロベシクルに封入体がロードされたか否かを確認することができる。
実施例9と同様の方法でOmpA、OmpC及びOmpFが過発現された大腸菌を製造した後、各大腸菌を1:1:1の比率で混ぜた後、実施例1及び実施例2の方法でOmpA、OmpC及びOmpFがロードされた原形質体マイクロベシクルを製造した。
細菌外膜タンパク質がロードされたマイクロベシクルのワクチン作用を調べるために、OmpA、OmpC及びOmpFがロードされた原形質体由来マイクロベシクル40μgをマウスの腹腔にそれぞれPBSと共に7日間隔で3回投与した。投与7日後、OmpAタンパク質に特異的な抗体が生成されたことを確認するために、マウスの目から血液を採取した後、室温で30分間保管し、4℃で1時間保管した。1300×gで20分間遠心分離して細胞を除去し、上澄み液を得た。
細菌原形質体由来マイクロベシクルを、癌細胞に対する抗原を伝達する運搬体として用いて、癌細胞に対する免疫反応を誘導し、癌ワクチンとして使用できるかを確認するために、黒色腫癌を引き起こす抗原の一つとして知られているMart−1タンパク質を発現する細菌をクローニングを介して作った。
(下線は制限酵素NdeIとSalIの認識配列を意味する)
実施例12で製造したMart−1タンパク質がロードされたマイクロベシクル25μgを7日間隔で3回マウスの腹腔に投与した。3回目の投与7日後にマウス黒色腫細胞株(B16BL6)1×106細胞をマウスの皮膚下に注射し、20日後に癌組織を分離した後、その重量を測定した。
原形質体の表面にヒトEGFをロードするために、バクテリア内膜タンパク質としてのPrsAを暗号化する塩基配列のN末端から290番目のアミノン酸のペプチド区域を暗号化する塩基配列と結合しようと思い、まずPrsAの公知のDNA塩基配列に基づいて終止コドン(stop codon)を除いて特定の制限酵素を人為的に挿入して、次のとおりプライマーを製作した。
(下線は制限酵素NdeIとXbaIの認識配列を意味する)
(下線は制限酵素XbaIとHindIIの認識配列を意味する)
EGF融合タンパク質がロードされたマイクロベシクルの細胞特異的伝達をin vitroで確認するために、24ウェルプレートにヒト非小細胞肺癌のA549細胞を2×104の量だけ接種した後、24ウェルプレートで24時間培養した。A549細胞は細胞膜にEGF受容体を多量発現している細胞である。
6ウェルプレートにヒト非小細胞肺癌のA549細胞を1.5×105の量だけ接種した後、6ウェルプレートで16時間培養した。PBSで2回洗浄した後、血清(serum)のない培地に変えた後、16時間培養した。16時間後、それぞれ10μg/mLの濃度で実施例14の方法によって製造したグラム陰性菌原形質体由来EGF融合タンパク質ローディングマイクロベシクルと、ロードしていないマイクロベシクルを処理した後、10分間培養した。PBSで洗浄した後、ホスファターゼ阻害剤の含まれたM−PER(Pierce)溶液を150μL入れ、細胞全体タンパク質(whole cell lysate)を得た。
実施例14の方法によってEGF融合タンパク質ローディングマイクロベシクルを製造した後、前記マイクロベシクル懸濁溶液に抗癌薬物としてのドキソルビシンを400μg/mLの濃度で添加し、よく混ぜた後、4℃で12時間培養した。12時間後、培養液を100,000×gで2時間超遠心分離した。沈殿物をTBSで懸濁し、ドキソルビシンがロードされたマイクロベシクルを得た。
実施例14の方法によってEGF融合タンパク質ローディングマイクロベシクルを製造した後、マウスの腹腔にそれぞれPBSと20μgのマイクロベシクルを投与した。投与7日後、EGFタンパク質に特異的な抗体が生成されたことを確認するために、マウスの目から血液を採取した後、室温で30分間保管し、4℃で1時間保管した。1,300×gで20分間遠心分離して細胞を除去し、上澄み液を得た。
原形質体の表面にヒトEGF受容体の細胞外部分をロードするために、バクテリア内膜タンパク質であるPrsAを暗号化する塩基配列のN末端から290番目のアミノ酸のペプチド区域を暗号化する塩基配列と結合しようと思い、実施例14で作られたpHCE−prsAベクターを用いた。
(下線は制限酵素XbaIとHindIIの認識配列を意味する)
実施例19で製造したEGF受容体融合タンパク質がロードされたマイクロベシクルと、そのタンパク質がロードされていないマイクロベシクルを準備した。96ウェルプレートを準備し、ウェルプレートにそれぞれ0、25、100ngとなるようにそれぞれのマイクロベシクルを仕込み、常温で12時間以上保管してコートした。1%BSA/PBSを100μL入れて1時間固定した。1時間後、ビオチンが付いているEGFを10ng/mLとなるように仕込み、2時間培養した。0.05%Tween−20の含まれたPBSで洗浄した後、ストレプトアビジン−PODで20分間培養し、BM−POD基質を入れて発色を誘導した。
原形質体の表面にHis−タグタンパク質をロードした細菌の原形質体由来マイクロベシクルを製造するために、pHCE−prsAベクターを用いた。前記pHCE−prsAベクターに制限酵素NdeIとHindIIIを用いて37℃で8時間処理した後、Quiaquickゲル精製キットで精製した。精製されたベクター挿入物を、既存のHis−タグタンパク質が融合されているpET−30a(+)ベクターに同一制限酵素を処理した後、精製して連結させて挿入した。このベクターを「pET−30a(+)−prsA−His6」と命名した。
6ウェルプレートに0.1%ゼラチン(gelatin)がコートされたカバーガラスを仕込み、カバーガラス上にヒト血管細胞としてのHUVEC細胞を1×105の量だけ接種した後、6ウェルプレートで16時間培養した。PBSで2回洗浄した後、培地2mLを仕込み、0、0.5、1、2μg/mLの濃度で、実施例1及び実施例2の方法によって製造したグラム陰性菌原形質体由来マイクロベシクルと実施例17の方法によって製造したドキソルビシンローディング原形質体由来マイクロベシクルをそれぞれ処理した後、24時間培養した。PBSで洗浄し、血清のない培地2mLを入れてセルトラッカー溶液(CellTracker solution)を5μMとなるように入れた後、30分間培養した。さらにPBSで洗浄した後、血清のある培地を2mL仕込み、さらに30分間培養した。カバーガラスを4%パラホルムアルデヒド2mLに入れて室温で10分間保管した。蛍光顕微鏡を用いて写真を撮り、生きている細胞の数を測定して図33に示した。
24ウェルプレートに0.1%ゼラチンがコートされたカバーガラスを入れ、カバーガラス上にマウス大腸癌26細胞株(mouse colon 26)を2×104の量だけ接種した後、24ウェルプレートで16時間培養した。
マウス大腸癌26細胞株1×106細胞をマウスの皮膚下に注射し、5日間生育させた。5日後、実施例17の方法によって製造したドキソルビシンがロードされたグラム陰性菌原形質体由来マイクロベシクル0μg、1μg、5μgを含むPBS溶液100μLを1週に2回ずつマウスの尾に注射し、癌組織の大きさを測定して図21に示した。癌組織の体積は最も長い長さ(l)とそれに垂直な長さ(s)を測定し、v=ls2/2の式で計算した。
Claims (7)
- 物質を供給するための薬学的組成物であって、
細胞壁を有する細菌細胞の原形質体に由来するマイクロベシクルを含み、
前記物質は、抗癌剤であって、
前記マイクロベシクルが由来する前記細胞は、前記マイクロベシクルが癌細胞または癌組織を標的にすることが可能なように形質転換された薬学的組成物。 - 前記マイクロベシクルが、細胞接合分子、抗体、標的誘導タンパク質、細胞膜融合タンパク質自体、及びこれらの融合タンパク質よりなる群から選ばれる一つ以上を発現するように形質転換された細胞の原形質体に由来するものである、請求項1に記載の薬学的組成物。
- 前記マイクロベシクルが、リガンドディスプレイ用タンパク質、リガンドディスプレイ用ペプチド、及びこれらの融合タンパク質よりなる群から選ばれる一つ以上を発現するように形質転換された細胞の原形質体に由来するものである、請求項1に記載の薬学的組成物。
- 前記マイクロベシクルが、リガンドトラップ用タンパク質、リガンドトラップ用ペプチド、及びこれらの融合タンパク質よりなる群から選ばれる一つ以上を発現するように形質転換された細胞の原形質体に由来するものである、請求項1に記載の薬学的組成物。
- 前記マイクロベシクルが、封入体(inclusion body)を有するマイクロベシクルである、請求項1に記載の薬学的組成物。
- 抗癌剤がロードされた、細胞壁を有する細菌細胞の原形質体由来マイクロベシクルの製造方法であって、
前記マイクロベシクルが由来する前記細胞は、前記マイクロベシクルが癌細胞または癌組織を標的にすることが可能なように形質転換されたものであり、
下記の段階を含む方法:
(a)細胞壁を有する細菌細胞に抗癌剤を外部からロードし、細胞壁を取り除いて原形質体を収得する段階、
(b)前記原形質体を含む懸濁液からマイクロベシクルを製造する段階、及び
(c)前記懸濁液から製造されたマイクロベシクルを分離する段階。 - 抗癌剤がロードされた、細胞壁を有する細菌細胞の原形質体由来マイクロベシクルの製造方法であって、
前記マイクロベシクルが由来する前記細胞は、前記マイクロベシクルが癌細胞または癌組織を標的にすることが可能なように形質転換されたものであり、
下記の段階を含む方法:
(a)細胞壁を有する細菌細胞から細胞壁を取り除いて原形質体を収得する段階、
(b)前記原形質体を含む懸濁液に抗癌剤を添加してマイクロベシクルを製造する段階、及び
(c)前記懸濁液から製造されたマイクロベシクルを分離する段階。
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR20100063527 | 2010-07-01 | ||
KR10-2010-0063527 | 2010-07-01 | ||
PCT/KR2011/004820 WO2012002759A2 (ko) | 2010-07-01 | 2011-06-30 | 세포의 원형질체에서 유래한 마이크로베시클 및 이의 용도 |
KR1020110065112A KR101232377B1 (ko) | 2010-07-01 | 2011-06-30 | 세포의 원형질체에서 유래한 마이크로베시클 및 이의 용도 |
KR10-2011-0065112 | 2011-06-30 |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2013534830A JP2013534830A (ja) | 2013-09-09 |
JP2013534830A5 JP2013534830A5 (ja) | 2014-03-06 |
JP5814363B2 true JP5814363B2 (ja) | 2015-11-17 |
Family
ID=45610101
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2013518258A Active JP5814363B2 (ja) | 2010-07-01 | 2011-06-30 | 細胞の原形質体に由来するマイクロベシクル及びその用途 |
Country Status (9)
Country | Link |
---|---|
US (2) | US9149542B2 (ja) |
EP (1) | EP2589377B1 (ja) |
JP (1) | JP5814363B2 (ja) |
KR (1) | KR101232377B1 (ja) |
CN (1) | CN103002879B (ja) |
AU (1) | AU2011271830B2 (ja) |
BR (1) | BR112013000024B1 (ja) |
RU (1) | RU2570636C2 (ja) |
WO (1) | WO2012002759A2 (ja) |
Families Citing this family (29)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20120315324A1 (en) | 2010-02-05 | 2012-12-13 | University Of Louisville Research Foundation, Inc. | Exosomal compositions and methods for the treatment of disease |
DK2686020T3 (en) | 2011-03-17 | 2017-05-01 | Univ Birmingham | REDIRECTED IMMUNTERY |
KR20120132183A (ko) * | 2011-05-27 | 2012-12-05 | 포항공과대학교 산학협력단 | 종양 조직에서 유래한 나노소포체 및 이를 이용한 암 백신 |
US20140308212A1 (en) | 2011-11-07 | 2014-10-16 | University Of Louisville Research Foundation, Inc. | Edible plant-derived microvesicle compositions for diagnosis and treatment of disease |
KR102118751B1 (ko) * | 2013-12-27 | 2020-06-03 | 코웨이 주식회사 | 탈분화 식물 프로토플라스트 내에 활성 물질이 인입된 구조체, 이의 제조방법 및 이를 포함하는 화장료 조성물 |
WO2015157652A1 (en) * | 2014-04-11 | 2015-10-15 | University Of Louisville Research Foundation, Inc. | Coated edible plant-derived microvesicle compositions and methods for using the same |
CN107429226A (zh) | 2015-01-06 | 2017-12-01 | 株式会社露太利温 | luterion及其分离和培养方法 |
KR101720851B1 (ko) * | 2015-01-29 | 2017-03-28 | 포항공과대학교 산학협력단 | 세포의 지질막에서 유래된 나노소포체 및 이의 용도 |
KR101747786B1 (ko) | 2015-03-09 | 2017-06-15 | 포항공과대학교 산학협력단 | 배아줄기세포에서 유래한 인공 나노베시클을 이용하여 세포 증식을 향상시키는 방법 |
KR20170011221A (ko) * | 2015-07-22 | 2017-02-02 | 이화여자대학교 산학협력단 | 클렙시엘라균 감염질환의 예방용 백신 |
KR101858840B1 (ko) | 2016-01-15 | 2018-05-16 | 단국대학교 천안캠퍼스 산학협력단 | 집먼지진드기 유래 알레르겐에 의한 과민반응 면역조절제 |
JP6704106B2 (ja) * | 2016-02-12 | 2020-06-03 | ノーベル化学宏業株式会社 | 原形質流動性増加作用を呈するフェノール誘導体 |
KR102085787B1 (ko) * | 2016-08-12 | 2020-03-06 | 주식회사 엠디헬스케어 | 바실러스 속 세균 유래 나노소포 및 이의 용도 |
US10815520B2 (en) | 2017-04-07 | 2020-10-27 | University Of Louisville Research Foundation, Inc. | Nanovesicles, methods, and systems for diagnosis and prognosis of cancer |
CN107142228A (zh) * | 2017-04-18 | 2017-09-08 | 浙江大学 | 一种大肠杆菌外膜囊泡的制备、载药方法与其在抗肿瘤中的应用 |
KR102109950B1 (ko) * | 2017-06-02 | 2020-05-12 | (주)엑솔런스바이오테크놀로지 | 체외충격파를 이용한 세포외소포체 내로의 표적물질 전달방법 |
KR102088555B1 (ko) * | 2017-08-29 | 2020-03-12 | 건국대학교 산학협력단 | 혈청 유래 엑소좀을 이용한 림프절 표적 지향형 약물 전달체 |
GB2574785A (en) | 2017-09-15 | 2019-12-25 | Jan Loetvall | Method and system for identifying membrane proteins on extracellular vesicles |
MX2020004883A (es) * | 2017-11-17 | 2020-08-06 | Codiak Biosciences Inc | Composiciones de exosomas modificados y metodos de cargar cargas de exosomas luminales. |
KR102212335B1 (ko) * | 2018-03-21 | 2021-02-04 | ㈜로제타엑소좀 | 박테리아 유래이고 독성이 감소된 세포밖 소포체 및 이의 용도 |
US20220080035A1 (en) * | 2019-01-09 | 2022-03-17 | Exocure Biosciences, Inc. | Bacteria-derived vesicles and uses thereof |
KR102636371B1 (ko) * | 2020-04-10 | 2024-02-19 | 한국과학기술연구원 | 신규 재조합 엑소좀 및 그의 용도 |
CN113528450B (zh) * | 2020-04-22 | 2023-10-13 | 中国农业科学院作物科学研究所 | 一种水稻原生质体高效生物素标记体系的建立及应用 |
RU2771096C1 (ru) * | 2021-02-04 | 2022-04-26 | Гордейчук Владимир Евгеньевич | Способ выделения микровезикул из растений семейства амарантовых |
KR20220148567A (ko) * | 2021-04-29 | 2022-11-07 | 주식회사 서지넥스 | 약물전달물질로서의 간세포암 특이적 표적 엑소좀 조성물 및 이의 용도 |
KR102620197B1 (ko) * | 2021-04-30 | 2024-01-02 | 가톨릭대학교 산학협력단 | 약물전달물질로서의 대장암 특이적 표적 엑소좀 조성물 및 이의 용도 |
KR102659839B1 (ko) * | 2021-05-25 | 2024-04-22 | 연세대학교 원주산학협력단 | Cd47 양성 세포막 유래 나노입자, 이의 용도 및 이의 제조방법 |
CN114081957A (zh) * | 2021-11-02 | 2022-02-25 | 姜海涛 | 一种心脏靶向载药外泌体及其制备方法、应用和运载体 |
WO2023156532A1 (en) * | 2022-02-18 | 2023-08-24 | Servicio Andaluz De Salud | ISOLATED PLASMA MEMBRANE-DERIVED VESICLES (PMdV) FOR USE IN THE TREATMENT OF VIRAL INFECTIONS |
Family Cites Families (16)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB0007150D0 (en) | 2000-03-24 | 2000-05-17 | Lamellar Therapeutics Limited | Immunotherapeutic methods and compositions |
US7396822B2 (en) * | 2001-05-24 | 2008-07-08 | Vaxiion Therapeutics, Inc. | Immunogenic minicells and methods of use |
US20030211086A1 (en) * | 2001-06-05 | 2003-11-13 | Neil Berkley | Minicell-based selective absorption |
US20030224369A1 (en) * | 2002-02-25 | 2003-12-04 | Surber Mark W. | Reverse screening and target identification with minicells |
KR101455222B1 (ko) * | 2002-12-16 | 2014-10-31 | 글로브이뮨 | 면역 요법으로서의 효모계 백신 |
US20040011695A1 (en) * | 2003-06-24 | 2004-01-22 | Wright James H. | Anti-Splash, Anti-Spill Apparatus and Method for Holding Antiseptic Solution During a Surgical Procedure |
US7070826B2 (en) | 2003-07-15 | 2006-07-04 | Pacific Rim Marketing Limited | Process and formulation for producing a multipurpose, multi-functional apple base |
RS54149B1 (en) | 2004-02-02 | 2015-12-31 | Engeneic Molecular Delivery Pty Ltd. | COMPOSITIONS AND PROCEDURES IN VITRO AND IN VIVO, TARGETED MEDICINAL RELEASE IN Mammalian cells via intact minicells derived from bacteria |
JP2008501336A (ja) * | 2004-06-02 | 2008-01-24 | ソースフアーム・インコーポレイテツド | Rnaを含有する微小胞およびそのための方法 |
PT2682126T (pt) * | 2005-01-27 | 2017-02-28 | Children`S Hospital & Res Center At Oakland | Vacinas de vesícula com base em agn1870 para proteção de amplo espetro contra doenças causadas por neisseria meningitidis |
RU2306945C1 (ru) * | 2006-02-15 | 2007-09-27 | Автономная некоммерческая организация Научно-технический центр "Фармбиопресс" | Профилактическая композиция на основе веществ фенольной природы и фосфолипидов |
AR062223A1 (es) * | 2006-08-09 | 2008-10-22 | Glycart Biotechnology Ag | Moleculas de adhesion al antigeno que se adhieren a egfr, vectores que los codifican, y sus usos de estas |
EP1939218A1 (en) | 2006-12-29 | 2008-07-02 | Thrombotargets Europe, S.L. | Microvesicles derived from recombinant yeast having haemostatic activities and uses thereof |
ES2523098T3 (es) * | 2007-10-29 | 2014-11-20 | Fresenius Medical Care Deutschland Gmbh | Microvesícula (MV) derivada de células madre para su uso en la inhibición de la apoptosis inducida por un agente citostático |
BRPI0907050B1 (pt) * | 2008-02-01 | 2022-03-22 | The General Hospital Corporation | Método para detectar em um indivíduo a presença ou ausência de um ácido nucleico biomarcador predeterminado associado com câncer de próstata |
RU2373914C1 (ru) * | 2008-05-12 | 2009-11-27 | Илья Николаевич Медведев | Способ коррекции уровня микровезикул в крови при абдоминальном ожирении |
-
2011
- 2011-06-30 KR KR1020110065112A patent/KR101232377B1/ko active IP Right Grant
- 2011-06-30 JP JP2013518258A patent/JP5814363B2/ja active Active
- 2011-06-30 AU AU2011271830A patent/AU2011271830B2/en not_active Ceased
- 2011-06-30 WO PCT/KR2011/004820 patent/WO2012002759A2/ko active Application Filing
- 2011-06-30 CN CN201180033175.7A patent/CN103002879B/zh active Active
- 2011-06-30 BR BR112013000024-4A patent/BR112013000024B1/pt not_active IP Right Cessation
- 2011-06-30 RU RU2013104171/10A patent/RU2570636C2/ru active
- 2011-06-30 US US13/807,683 patent/US9149542B2/en active Active
- 2011-06-30 EP EP11801164.2A patent/EP2589377B1/en active Active
-
2015
- 2015-03-02 US US14/635,379 patent/US9084830B2/en active Active
Also Published As
Publication number | Publication date |
---|---|
RU2013104171A (ru) | 2014-08-10 |
EP2589377A4 (en) | 2014-11-26 |
EP2589377B1 (en) | 2018-10-17 |
US20130115241A1 (en) | 2013-05-09 |
AU2011271830B2 (en) | 2014-08-14 |
RU2570636C2 (ru) | 2015-12-10 |
EP2589377A2 (en) | 2013-05-08 |
WO2012002759A2 (ko) | 2012-01-05 |
US9149542B2 (en) | 2015-10-06 |
KR20120002942A (ko) | 2012-01-09 |
CN103002879A (zh) | 2013-03-27 |
KR101232377B1 (ko) | 2013-02-13 |
US20150174271A1 (en) | 2015-06-25 |
BR112013000024A2 (pt) | 2016-05-10 |
BR112013000024B1 (pt) | 2021-11-23 |
US9084830B2 (en) | 2015-07-21 |
CN103002879B (zh) | 2016-04-20 |
JP2013534830A (ja) | 2013-09-09 |
WO2012002759A3 (ko) | 2012-05-03 |
AU2011271830A1 (en) | 2013-01-10 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP5814363B2 (ja) | 細胞の原形質体に由来するマイクロベシクル及びその用途 | |
US10675244B2 (en) | Microvesicles derived from nucleated, mammalian cells and use thereof | |
JP5635690B2 (ja) | 細菌由来マイクロベシクルを用いた癌治療及び癌診断方法 | |
Das et al. | Exosome as a novel shuttle for delivery of therapeutics across biological barriers | |
Richter et al. | Approaches to surface engineering of extracellular vesicles | |
He et al. | Exosomal targeting and its potential clinical application | |
Ohno et al. | Exosome-mediated targeted delivery of miRNAs | |
US20210353769A1 (en) | Surface modified extracellular vesicles | |
Oshchepkova et al. | Extracellular vesicles for therapeutic nucleic acid delivery: loading strategies and challenges | |
Liu et al. | Advances on non-genetic cell membrane engineering for biomedical applications | |
Zhu et al. | Tumor-microenvironment Responsive Targeted Exosome-like Nanovesicles From Dunaliella Salina for Enhancing Gene/immune Combination Therapy | |
Stranford | Engineering Extracellular Vesicles for Targeted Delivery of Therapeutic Biomolecules | |
JP2024015870A (ja) | Car-t細胞を作製する方法、car-t細胞作製用キット及びcar-t細胞含有率を向上させる方法 | |
Charoenviriyakul | Evaluation of the pharmacokinetic and pharmaceutical characteristics of exosomes for the development of exosome-based drug delivery carrier. |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20131220 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20140604 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20140904 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20150317 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20150713 |
|
A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20150721 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20150911 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20150917 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 5814363 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |