JP6533797B2 - 抗lystによる免疫調整のための組成物及び方法 - Google Patents
抗lystによる免疫調整のための組成物及び方法 Download PDFInfo
- Publication number
- JP6533797B2 JP6533797B2 JP2016565483A JP2016565483A JP6533797B2 JP 6533797 B2 JP6533797 B2 JP 6533797B2 JP 2016565483 A JP2016565483 A JP 2016565483A JP 2016565483 A JP2016565483 A JP 2016565483A JP 6533797 B2 JP6533797 B2 JP 6533797B2
- Authority
- JP
- Japan
- Prior art keywords
- lyst
- antibody
- composition
- subject
- vascular
- 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
- 239000000203 mixture Substances 0.000 title claims description 145
- 238000000034 method Methods 0.000 title claims description 121
- 230000008102 immune modulation Effects 0.000 title 1
- 239000003112 inhibitor Substances 0.000 claims description 205
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 82
- 210000001519 tissue Anatomy 0.000 claims description 78
- 230000002792 vascular Effects 0.000 claims description 77
- 108090000623 proteins and genes Proteins 0.000 claims description 70
- 150000007523 nucleic acids Chemical class 0.000 claims description 68
- 210000002540 macrophage Anatomy 0.000 claims description 63
- 102000039446 nucleic acids Human genes 0.000 claims description 63
- 108020004707 nucleic acids Proteins 0.000 claims description 63
- 102000004169 proteins and genes Human genes 0.000 claims description 62
- 108010038512 Platelet-Derived Growth Factor Proteins 0.000 claims description 46
- 102000010780 Platelet-Derived Growth Factor Human genes 0.000 claims description 46
- 238000012384 transportation and delivery Methods 0.000 claims description 44
- 208000031481 Pathologic Constriction Diseases 0.000 claims description 43
- 208000014674 injury Diseases 0.000 claims description 43
- 230000036262 stenosis Effects 0.000 claims description 42
- 208000037804 stenosis Diseases 0.000 claims description 42
- 238000001356 surgical procedure Methods 0.000 claims description 41
- 208000037803 restenosis Diseases 0.000 claims description 40
- 208000035475 disorder Diseases 0.000 claims description 39
- 239000003814 drug Substances 0.000 claims description 37
- 210000004204 blood vessel Anatomy 0.000 claims description 36
- 238000011282 treatment Methods 0.000 claims description 36
- 239000003981 vehicle Substances 0.000 claims description 31
- 230000014509 gene expression Effects 0.000 claims description 28
- 206010016654 Fibrosis Diseases 0.000 claims description 27
- 239000007943 implant Substances 0.000 claims description 27
- 230000037390 scarring Effects 0.000 claims description 27
- 108020004459 Small interfering RNA Proteins 0.000 claims description 26
- 230000008595 infiltration Effects 0.000 claims description 26
- 238000001764 infiltration Methods 0.000 claims description 26
- 230000002062 proliferating effect Effects 0.000 claims description 26
- 230000010118 platelet activation Effects 0.000 claims description 25
- 230000015572 biosynthetic process Effects 0.000 claims description 24
- 239000002502 liposome Substances 0.000 claims description 24
- 230000004761 fibrosis Effects 0.000 claims description 23
- 239000000463 material Substances 0.000 claims description 23
- 108090000994 Catalytic RNA Proteins 0.000 claims description 22
- 102000053642 Catalytic RNA Human genes 0.000 claims description 22
- 230000008692 neointimal formation Effects 0.000 claims description 22
- 230000002265 prevention Effects 0.000 claims description 22
- 108091092562 ribozyme Proteins 0.000 claims description 22
- 238000009472 formulation Methods 0.000 claims description 21
- 238000002513 implantation Methods 0.000 claims description 21
- 231100000241 scar Toxicity 0.000 claims description 21
- 108091023037 Aptamer Proteins 0.000 claims description 20
- 230000000692 anti-sense effect Effects 0.000 claims description 19
- 238000002399 angioplasty Methods 0.000 claims description 18
- 230000029663 wound healing Effects 0.000 claims description 18
- 239000000427 antigen Substances 0.000 claims description 17
- 108091007433 antigens Proteins 0.000 claims description 17
- 102000036639 antigens Human genes 0.000 claims description 17
- -1 antisense molecule Proteins 0.000 claims description 17
- 208000019425 cirrhosis of liver Diseases 0.000 claims description 16
- 239000003102 growth factor Substances 0.000 claims description 16
- 229940124597 therapeutic agent Drugs 0.000 claims description 16
- 102000004127 Cytokines Human genes 0.000 claims description 15
- 108090000695 Cytokines Proteins 0.000 claims description 15
- 241000282414 Homo sapiens Species 0.000 claims description 15
- 230000015100 lysosomal transport Effects 0.000 claims description 15
- 230000009467 reduction Effects 0.000 claims description 15
- 108010012236 Chemokines Proteins 0.000 claims description 13
- 102000019034 Chemokines Human genes 0.000 claims description 13
- 230000009368 gene silencing by RNA Effects 0.000 claims description 13
- 230000035876 healing Effects 0.000 claims description 13
- 239000002245 particle Substances 0.000 claims description 13
- 208000005069 pulmonary fibrosis Diseases 0.000 claims description 13
- 239000008194 pharmaceutical composition Substances 0.000 claims description 12
- 108010021625 Immunoglobulin Fragments Proteins 0.000 claims description 11
- 102000008394 Immunoglobulin Fragments Human genes 0.000 claims description 11
- 208000034827 Neointima Diseases 0.000 claims description 11
- 230000037396 body weight Effects 0.000 claims description 11
- 108091070501 miRNA Proteins 0.000 claims description 11
- 239000002679 microRNA Substances 0.000 claims description 11
- 239000011859 microparticle Substances 0.000 claims description 11
- 208000002260 Keloid Diseases 0.000 claims description 10
- 108091030071 RNAI Proteins 0.000 claims description 10
- 102000004887 Transforming Growth Factor beta Human genes 0.000 claims description 10
- 108090001012 Transforming Growth Factor beta Proteins 0.000 claims description 10
- 238000000576 coating method Methods 0.000 claims description 10
- 239000000839 emulsion Substances 0.000 claims description 10
- 210000001117 keloid Anatomy 0.000 claims description 10
- 208000024248 Vascular System injury Diseases 0.000 claims description 9
- 208000012339 Vascular injury Diseases 0.000 claims description 9
- 239000002955 immunomodulating agent Substances 0.000 claims description 9
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 claims description 9
- 230000008733 trauma Effects 0.000 claims description 9
- 108090001030 Lipoproteins Proteins 0.000 claims description 8
- 102000004895 Lipoproteins Human genes 0.000 claims description 8
- 208000007536 Thrombosis Diseases 0.000 claims description 8
- 239000002246 antineoplastic agent Substances 0.000 claims description 8
- 230000001969 hypertrophic effect Effects 0.000 claims description 8
- 239000002105 nanoparticle Substances 0.000 claims description 8
- 200000000007 Arterial disease Diseases 0.000 claims description 7
- 239000000969 carrier Substances 0.000 claims description 7
- 239000000499 gel Substances 0.000 claims description 7
- 238000010348 incorporation Methods 0.000 claims description 7
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 6
- 206010023330 Keloid scar Diseases 0.000 claims description 6
- 229940127089 cytotoxic agent Drugs 0.000 claims description 6
- 229960003444 immunosuppressant agent Drugs 0.000 claims description 6
- 239000003018 immunosuppressive agent Substances 0.000 claims description 6
- 239000000693 micelle Substances 0.000 claims description 6
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 claims description 6
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 claims description 6
- 229960003552 other antineoplastic agent in atc Drugs 0.000 claims description 6
- 239000002294 steroidal antiinflammatory agent Substances 0.000 claims description 6
- 230000003637 steroidlike Effects 0.000 claims description 6
- 206010003178 Arterial thrombosis Diseases 0.000 claims description 5
- 206010047249 Venous thrombosis Diseases 0.000 claims description 5
- 239000002041 carbon nanotube Substances 0.000 claims description 5
- 229910021393 carbon nanotube Inorganic materials 0.000 claims description 5
- 210000003709 heart valve Anatomy 0.000 claims description 5
- 239000011248 coating agent Substances 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 238000005538 encapsulation Methods 0.000 claims description 4
- 239000013604 expression vector Substances 0.000 claims description 4
- 230000036573 scar formation Effects 0.000 claims description 4
- 230000009772 tissue formation Effects 0.000 claims description 4
- 238000007631 vascular surgery Methods 0.000 claims description 4
- 230000009787 cardiac fibrosis Effects 0.000 claims description 3
- 208000010125 myocardial infarction Diseases 0.000 claims description 3
- 201000002793 renal fibrosis Diseases 0.000 claims description 3
- 230000006051 NK cell activation Effects 0.000 claims 6
- 210000004027 cell Anatomy 0.000 description 63
- 241000699670 Mus sp. Species 0.000 description 54
- 208000027418 Wounds and injury Diseases 0.000 description 43
- 201000010099 disease Diseases 0.000 description 43
- 230000006378 damage Effects 0.000 description 39
- 230000006870 function Effects 0.000 description 36
- 210000001772 blood platelet Anatomy 0.000 description 27
- 230000000694 effects Effects 0.000 description 24
- 101150055724 LYST gene Proteins 0.000 description 23
- 206010020718 hyperplasia Diseases 0.000 description 22
- 230000008569 process Effects 0.000 description 22
- 150000001413 amino acids Chemical group 0.000 description 21
- 239000003795 chemical substances by application Substances 0.000 description 21
- 238000011161 development Methods 0.000 description 21
- 230000018109 developmental process Effects 0.000 description 21
- 229940079593 drug Drugs 0.000 description 20
- 210000004072 lung Anatomy 0.000 description 16
- 230000035772 mutation Effects 0.000 description 15
- 230000004044 response Effects 0.000 description 15
- 208000024891 symptom Diseases 0.000 description 15
- 239000013598 vector Substances 0.000 description 15
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 14
- 229920000642 polymer Polymers 0.000 description 14
- 239000004055 small Interfering RNA Substances 0.000 description 14
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 13
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 13
- 230000004054 inflammatory process Effects 0.000 description 13
- 206010061218 Inflammation Diseases 0.000 description 12
- 230000004913 activation Effects 0.000 description 12
- 238000002347 injection Methods 0.000 description 12
- 239000007924 injection Substances 0.000 description 12
- 210000004185 liver Anatomy 0.000 description 12
- 238000004519 manufacturing process Methods 0.000 description 12
- 229920001184 polypeptide Polymers 0.000 description 12
- 108090000765 processed proteins & peptides Proteins 0.000 description 12
- 102000004196 processed proteins & peptides Human genes 0.000 description 12
- 230000017423 tissue regeneration Effects 0.000 description 12
- 206010028980 Neoplasm Diseases 0.000 description 11
- 210000002808 connective tissue Anatomy 0.000 description 11
- 210000002744 extracellular matrix Anatomy 0.000 description 11
- 230000000893 fibroproliferative effect Effects 0.000 description 11
- 230000003176 fibrotic effect Effects 0.000 description 11
- 230000012010 growth Effects 0.000 description 11
- 230000008439 repair process Effects 0.000 description 11
- 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 10
- 210000004369 blood Anatomy 0.000 description 10
- 239000008280 blood Substances 0.000 description 10
- 230000004087 circulation Effects 0.000 description 10
- 230000008021 deposition Effects 0.000 description 10
- 239000012634 fragment Substances 0.000 description 10
- 230000005764 inhibitory process Effects 0.000 description 10
- 230000035755 proliferation Effects 0.000 description 10
- 230000002829 reductive effect Effects 0.000 description 10
- 201000001320 Atherosclerosis Diseases 0.000 description 9
- 206010052428 Wound Diseases 0.000 description 9
- 229940024606 amino acid Drugs 0.000 description 9
- 210000002950 fibroblast Anatomy 0.000 description 9
- 230000006698 induction Effects 0.000 description 9
- 239000011159 matrix material Substances 0.000 description 9
- 230000007246 mechanism Effects 0.000 description 9
- 230000001404 mediated effect Effects 0.000 description 9
- 210000000056 organ Anatomy 0.000 description 9
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 9
- 239000000243 solution Substances 0.000 description 9
- 210000002889 endothelial cell Anatomy 0.000 description 8
- 230000001965 increasing effect Effects 0.000 description 8
- 108020004999 messenger RNA Proteins 0.000 description 8
- 102000008186 Collagen Human genes 0.000 description 7
- 108010035532 Collagen Proteins 0.000 description 7
- 108091028043 Nucleic acid sequence Proteins 0.000 description 7
- 239000000443 aerosol Substances 0.000 description 7
- 229920001436 collagen Polymers 0.000 description 7
- 150000001875 compounds Chemical class 0.000 description 7
- 230000028709 inflammatory response Effects 0.000 description 7
- 239000010410 layer Substances 0.000 description 7
- 239000003446 ligand Substances 0.000 description 7
- 150000002632 lipids Chemical class 0.000 description 7
- 210000003712 lysosome Anatomy 0.000 description 7
- 230000001868 lysosomic effect Effects 0.000 description 7
- 210000001616 monocyte Anatomy 0.000 description 7
- 230000002685 pulmonary effect Effects 0.000 description 7
- 230000011664 signaling Effects 0.000 description 7
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 description 7
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 7
- 239000000758 substrate Substances 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 6
- 230000034994 death Effects 0.000 description 6
- 231100000517 death Toxicity 0.000 description 6
- 230000003511 endothelial effect Effects 0.000 description 6
- 238000005516 engineering process Methods 0.000 description 6
- 210000002216 heart Anatomy 0.000 description 6
- 210000002865 immune cell Anatomy 0.000 description 6
- 210000000987 immune system Anatomy 0.000 description 6
- 210000004969 inflammatory cell Anatomy 0.000 description 6
- 230000002757 inflammatory effect Effects 0.000 description 6
- 230000002401 inhibitory effect Effects 0.000 description 6
- 238000001990 intravenous administration Methods 0.000 description 6
- 210000000265 leukocyte Anatomy 0.000 description 6
- 230000009826 neoplastic cell growth Effects 0.000 description 6
- 230000001737 promoting effect Effects 0.000 description 6
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 description 6
- 230000028327 secretion Effects 0.000 description 6
- 229960002930 sirolimus Drugs 0.000 description 6
- 230000009885 systemic effect Effects 0.000 description 6
- 230000008685 targeting Effects 0.000 description 6
- 230000001225 therapeutic effect Effects 0.000 description 6
- 230000008719 thickening Effects 0.000 description 6
- 208000037816 tissue injury Diseases 0.000 description 6
- 210000003462 vein Anatomy 0.000 description 6
- 210000001631 vena cava inferior Anatomy 0.000 description 6
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 5
- 108020004414 DNA Proteins 0.000 description 5
- 241000699666 Mus <mouse, genus> Species 0.000 description 5
- 108090000190 Thrombin Proteins 0.000 description 5
- 230000002411 adverse Effects 0.000 description 5
- 230000008827 biological function Effects 0.000 description 5
- 210000001185 bone marrow Anatomy 0.000 description 5
- 230000015556 catabolic process Effects 0.000 description 5
- 230000004663 cell proliferation Effects 0.000 description 5
- 230000003399 chemotactic effect Effects 0.000 description 5
- 210000000038 chest Anatomy 0.000 description 5
- 230000001684 chronic effect Effects 0.000 description 5
- 230000000875 corresponding effect Effects 0.000 description 5
- 238000006731 degradation reaction Methods 0.000 description 5
- 230000028993 immune response Effects 0.000 description 5
- 230000001976 improved effect Effects 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 5
- 230000000670 limiting effect Effects 0.000 description 5
- 208000019423 liver disease Diseases 0.000 description 5
- 230000007774 longterm Effects 0.000 description 5
- 210000000440 neutrophil Anatomy 0.000 description 5
- 230000037361 pathway Effects 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 238000011069 regeneration method Methods 0.000 description 5
- 210000003491 skin Anatomy 0.000 description 5
- 230000000638 stimulation Effects 0.000 description 5
- 229960004072 thrombin Drugs 0.000 description 5
- 238000013518 transcription Methods 0.000 description 5
- 230000035897 transcription Effects 0.000 description 5
- 210000004509 vascular smooth muscle cell Anatomy 0.000 description 5
- 210000005166 vasculature Anatomy 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 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 4
- 102000009123 Fibrin Human genes 0.000 description 4
- 108010073385 Fibrin Proteins 0.000 description 4
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical group CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 4
- 101001018064 Homo sapiens Lysosomal-trafficking regulator Proteins 0.000 description 4
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 4
- 108091008606 PDGF receptors Proteins 0.000 description 4
- 102000011653 Platelet-Derived Growth Factor Receptors Human genes 0.000 description 4
- 206010039710 Scleroderma Diseases 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 230000002159 abnormal effect Effects 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
- 239000013543 active substance Substances 0.000 description 4
- 125000000129 anionic group Chemical group 0.000 description 4
- 229940127218 antiplatelet drug Drugs 0.000 description 4
- 210000001367 artery Anatomy 0.000 description 4
- 230000004071 biological effect Effects 0.000 description 4
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 4
- 230000007882 cirrhosis Effects 0.000 description 4
- 230000000295 complement effect Effects 0.000 description 4
- 238000012377 drug delivery Methods 0.000 description 4
- 238000013171 endarterectomy Methods 0.000 description 4
- 229950003499 fibrin Drugs 0.000 description 4
- 210000004024 hepatic stellate cell Anatomy 0.000 description 4
- 230000002519 immonomodulatory effect Effects 0.000 description 4
- 238000011534 incubation Methods 0.000 description 4
- 230000003993 interaction Effects 0.000 description 4
- 239000004005 microsphere Substances 0.000 description 4
- 230000007935 neutral effect Effects 0.000 description 4
- 230000001575 pathological effect Effects 0.000 description 4
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 4
- 230000008929 regeneration Effects 0.000 description 4
- 230000001177 retroviral effect Effects 0.000 description 4
- 210000003752 saphenous vein Anatomy 0.000 description 4
- 230000019491 signal transduction Effects 0.000 description 4
- 150000003384 small molecules Chemical class 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 230000000699 topical effect Effects 0.000 description 4
- 238000013519 translation Methods 0.000 description 4
- 206010000050 Abdominal adhesions Diseases 0.000 description 3
- 206010003226 Arteriovenous fistula Diseases 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- 108010006654 Bleomycin Proteins 0.000 description 3
- 241001631457 Cannula Species 0.000 description 3
- 201000004315 EAST syndrome Diseases 0.000 description 3
- 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 206010067125 Liver injury Diseases 0.000 description 3
- 210000004322 M2 macrophage Anatomy 0.000 description 3
- 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 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 238000012228 RNA interference-mediated gene silencing Methods 0.000 description 3
- 108020004566 Transfer RNA Proteins 0.000 description 3
- 238000009825 accumulation Methods 0.000 description 3
- 230000000735 allogeneic effect Effects 0.000 description 3
- 230000001028 anti-proliverative effect Effects 0.000 description 3
- 229960001561 bleomycin Drugs 0.000 description 3
- 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 3
- 230000000903 blocking effect Effects 0.000 description 3
- 125000002091 cationic group Chemical group 0.000 description 3
- 230000035602 clotting Effects 0.000 description 3
- 238000007887 coronary angioplasty Methods 0.000 description 3
- 238000012217 deletion Methods 0.000 description 3
- 230000037430 deletion Effects 0.000 description 3
- 208000037765 diseases and disorders Diseases 0.000 description 3
- 231100000673 dose–response relationship Toxicity 0.000 description 3
- 239000012636 effector Substances 0.000 description 3
- 210000003038 endothelium Anatomy 0.000 description 3
- 230000036541 health Effects 0.000 description 3
- 229940121354 immunomodulator Drugs 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 238000011813 knockout mouse model Methods 0.000 description 3
- 230000003902 lesion Effects 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 229960000485 methotrexate Drugs 0.000 description 3
- 238000013508 migration Methods 0.000 description 3
- 210000000651 myofibroblast Anatomy 0.000 description 3
- 210000000822 natural killer cell Anatomy 0.000 description 3
- 239000002773 nucleotide Substances 0.000 description 3
- 125000003729 nucleotide group Chemical group 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- 239000000106 platelet aggregation inhibitor Substances 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 230000000770 proinflammatory effect Effects 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 230000001172 regenerating effect Effects 0.000 description 3
- 238000007634 remodeling Methods 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 210000002345 respiratory system Anatomy 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 241000894007 species Species 0.000 description 3
- 210000000952 spleen Anatomy 0.000 description 3
- 239000007921 spray Substances 0.000 description 3
- 238000010561 standard procedure Methods 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 238000012385 systemic delivery Methods 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
- 230000014616 translation Effects 0.000 description 3
- 238000002054 transplantation Methods 0.000 description 3
- 230000006444 vascular growth Effects 0.000 description 3
- 229960004528 vincristine Drugs 0.000 description 3
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 3
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 3
- CITHEXJVPOWHKC-UUWRZZSWSA-N 1,2-di-O-myristoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCCCC CITHEXJVPOWHKC-UUWRZZSWSA-N 0.000 description 2
- KILNVBDSWZSGLL-KXQOOQHDSA-N 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCCCCCC KILNVBDSWZSGLL-KXQOOQHDSA-N 0.000 description 2
- TZCPCKNHXULUIY-RGULYWFUSA-N 1,2-distearoyl-sn-glycero-3-phosphoserine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OC[C@H](N)C(O)=O)OC(=O)CCCCCCCCCCCCCCCCC TZCPCKNHXULUIY-RGULYWFUSA-N 0.000 description 2
- 208000004998 Abdominal Pain Diseases 0.000 description 2
- 102000007469 Actins Human genes 0.000 description 2
- 108010085238 Actins Proteins 0.000 description 2
- 206010002329 Aneurysm Diseases 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 208000037260 Atherosclerotic Plaque Diseases 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- 206010053567 Coagulopathies Diseases 0.000 description 2
- 108010092160 Dactinomycin Proteins 0.000 description 2
- 208000005189 Embolism Diseases 0.000 description 2
- HKVAMNSJSFKALM-GKUWKFKPSA-N Everolimus Chemical compound C1C[C@@H](OCCO)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 HKVAMNSJSFKALM-GKUWKFKPSA-N 0.000 description 2
- ZWZWYGMENQVNFU-UHFFFAOYSA-N Glycerophosphorylserin Natural products OC(=O)C(N)COP(O)(=O)OCC(O)CO ZWZWYGMENQVNFU-UHFFFAOYSA-N 0.000 description 2
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 2
- 206010019663 Hepatic failure Diseases 0.000 description 2
- 101001046686 Homo sapiens Integrin alpha-M Proteins 0.000 description 2
- 101000692455 Homo sapiens Platelet-derived growth factor receptor beta Proteins 0.000 description 2
- 201000009794 Idiopathic Pulmonary Fibrosis Diseases 0.000 description 2
- 206010061598 Immunodeficiency Diseases 0.000 description 2
- 102100022338 Integrin alpha-M Human genes 0.000 description 2
- 208000029523 Interstitial Lung disease Diseases 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 2
- 239000005517 L01XE01 - Imatinib Substances 0.000 description 2
- 239000000232 Lipid Bilayer Substances 0.000 description 2
- 102100033472 Lysosomal-trafficking regulator Human genes 0.000 description 2
- 206010027476 Metastases Diseases 0.000 description 2
- 241000699660 Mus musculus Species 0.000 description 2
- 108010021466 Mutant Proteins Proteins 0.000 description 2
- 102000008300 Mutant Proteins Human genes 0.000 description 2
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 description 2
- 206010029113 Neovascularisation Diseases 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- 108091034117 Oligonucleotide Proteins 0.000 description 2
- 229930012538 Paclitaxel Natural products 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- 206010034238 Pelvic adhesions Diseases 0.000 description 2
- 208000030831 Peripheral arterial occlusive disease Diseases 0.000 description 2
- 206010073391 Platelet dysfunction Diseases 0.000 description 2
- 102100024616 Platelet endothelial cell adhesion molecule Human genes 0.000 description 2
- 102100026547 Platelet-derived growth factor receptor beta Human genes 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 229920000954 Polyglycolide Polymers 0.000 description 2
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 2
- 208000004756 Respiratory Insufficiency Diseases 0.000 description 2
- 102000004167 Ribonuclease P Human genes 0.000 description 2
- 108090000621 Ribonuclease P Proteins 0.000 description 2
- 206010039491 Sarcoma Diseases 0.000 description 2
- 229930182558 Sterol Natural products 0.000 description 2
- 208000002223 abdominal aortic aneurysm Diseases 0.000 description 2
- 238000012084 abdominal surgery Methods 0.000 description 2
- 230000001594 aberrant effect Effects 0.000 description 2
- 230000005856 abnormality Effects 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
- 230000010398 acute inflammatory response Effects 0.000 description 2
- 238000007792 addition Methods 0.000 description 2
- 230000002776 aggregation Effects 0.000 description 2
- 238000004220 aggregation Methods 0.000 description 2
- 229910045601 alloy Inorganic materials 0.000 description 2
- 239000000956 alloy Substances 0.000 description 2
- 229910052782 aluminium Inorganic materials 0.000 description 2
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 230000000340 anti-metabolite Effects 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- 229940100197 antimetabolite Drugs 0.000 description 2
- 239000002256 antimetabolite Substances 0.000 description 2
- 229940034982 antineoplastic agent Drugs 0.000 description 2
- 208000007474 aortic aneurysm Diseases 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 230000003143 atherosclerotic effect Effects 0.000 description 2
- 230000017531 blood circulation Effects 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 210000003123 bronchiole Anatomy 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 210000001715 carotid artery Anatomy 0.000 description 2
- 238000013172 carotid endarterectomy Methods 0.000 description 2
- 230000010261 cell growth Effects 0.000 description 2
- 230000012292 cell migration Effects 0.000 description 2
- 239000002975 chemoattractant Substances 0.000 description 2
- 235000012000 cholesterol Nutrition 0.000 description 2
- 208000037976 chronic inflammation Diseases 0.000 description 2
- 230000012085 chronic inflammatory response Effects 0.000 description 2
- 208000020832 chronic kidney disease Diseases 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 238000011260 co-administration Methods 0.000 description 2
- 230000015271 coagulation Effects 0.000 description 2
- 238000005345 coagulation Methods 0.000 description 2
- 238000010276 construction Methods 0.000 description 2
- 238000013270 controlled release Methods 0.000 description 2
- 229920001577 copolymer Polymers 0.000 description 2
- 208000029078 coronary artery disease Diseases 0.000 description 2
- 210000004351 coronary vessel Anatomy 0.000 description 2
- 230000002596 correlated effect Effects 0.000 description 2
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 2
- 229960000640 dactinomycin Drugs 0.000 description 2
- 230000003111 delayed effect Effects 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 229960003724 dimyristoylphosphatidylcholine Drugs 0.000 description 2
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 229960004679 doxorubicin Drugs 0.000 description 2
- 230000008482 dysregulation Effects 0.000 description 2
- 230000002526 effect on cardiovascular system Effects 0.000 description 2
- 230000002500 effect on skin Effects 0.000 description 2
- 230000008030 elimination Effects 0.000 description 2
- 238000003379 elimination reaction Methods 0.000 description 2
- 208000028208 end stage renal disease Diseases 0.000 description 2
- 201000000523 end stage renal failure Diseases 0.000 description 2
- 230000002708 enhancing effect Effects 0.000 description 2
- 210000002919 epithelial cell Anatomy 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 229960005167 everolimus Drugs 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 206010016256 fatigue Diseases 0.000 description 2
- 239000000835 fiber Substances 0.000 description 2
- 108060002894 fibrillar collagen Proteins 0.000 description 2
- 102000013373 fibrillar collagen Human genes 0.000 description 2
- 238000000684 flow cytometry Methods 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 230000030279 gene silencing Effects 0.000 description 2
- 238000012226 gene silencing method Methods 0.000 description 2
- 238000001631 haemodialysis Methods 0.000 description 2
- 238000007490 hematoxylin and eosin (H&E) staining Methods 0.000 description 2
- 230000000322 hemodialysis Effects 0.000 description 2
- 229960002897 heparin Drugs 0.000 description 2
- 229920000669 heparin Polymers 0.000 description 2
- 210000003494 hepatocyte Anatomy 0.000 description 2
- 102000049826 human LYST Human genes 0.000 description 2
- 239000000017 hydrogel Substances 0.000 description 2
- KTUFNOKKBVMGRW-UHFFFAOYSA-N imatinib Chemical compound C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 KTUFNOKKBVMGRW-UHFFFAOYSA-N 0.000 description 2
- 229960002411 imatinib Drugs 0.000 description 2
- 230000016784 immunoglobulin production Effects 0.000 description 2
- 230000002055 immunohistochemical effect Effects 0.000 description 2
- 238000003364 immunohistochemistry Methods 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 230000000977 initiatory effect Effects 0.000 description 2
- 208000036971 interstitial lung disease 2 Diseases 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 230000002427 irreversible effect Effects 0.000 description 2
- 208000028867 ischemia Diseases 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 231100000835 liver failure Toxicity 0.000 description 2
- 208000007903 liver failure Diseases 0.000 description 2
- 210000005265 lung cell Anatomy 0.000 description 2
- 229920002521 macromolecule Polymers 0.000 description 2
- 230000036210 malignancy Effects 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 description 2
- 230000009401 metastasis Effects 0.000 description 2
- 239000003094 microcapsule Substances 0.000 description 2
- 230000005012 migration Effects 0.000 description 2
- 230000001617 migratory effect Effects 0.000 description 2
- 229960004857 mitomycin Drugs 0.000 description 2
- 210000004980 monocyte derived macrophage Anatomy 0.000 description 2
- 238000010172 mouse model Methods 0.000 description 2
- 210000004877 mucosa Anatomy 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- 229910001000 nickel titanium Inorganic materials 0.000 description 2
- 229910052758 niobium Inorganic materials 0.000 description 2
- 239000010955 niobium Substances 0.000 description 2
- GUCVJGMIXFAOAE-UHFFFAOYSA-N niobium atom Chemical compound [Nb] GUCVJGMIXFAOAE-UHFFFAOYSA-N 0.000 description 2
- 238000010899 nucleation Methods 0.000 description 2
- 229960001592 paclitaxel Drugs 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 230000035515 penetration Effects 0.000 description 2
- 210000003024 peritoneal macrophage Anatomy 0.000 description 2
- 229940124531 pharmaceutical excipient Drugs 0.000 description 2
- 239000002953 phosphate buffered saline Substances 0.000 description 2
- 150000003904 phospholipids Chemical class 0.000 description 2
- 108010017843 platelet-derived growth factor A Proteins 0.000 description 2
- 108010017992 platelet-derived growth factor C Proteins 0.000 description 2
- 210000004623 platelet-rich plasma Anatomy 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 229920001610 polycaprolactone Polymers 0.000 description 2
- 239000004632 polycaprolactone Substances 0.000 description 2
- 239000004633 polyglycolic acid Substances 0.000 description 2
- 239000004626 polylactic acid Substances 0.000 description 2
- 229920000136 polysorbate Polymers 0.000 description 2
- 229920001343 polytetrafluoroethylene Polymers 0.000 description 2
- 239000004810 polytetrafluoroethylene Substances 0.000 description 2
- 230000004481 post-translational protein modification Effects 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 239000013615 primer Substances 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 239000003805 procoagulant Substances 0.000 description 2
- 230000000750 progressive effect Effects 0.000 description 2
- 238000011321 prophylaxis Methods 0.000 description 2
- 230000000541 pulsatile effect Effects 0.000 description 2
- 210000002321 radial artery Anatomy 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 230000010076 replication Effects 0.000 description 2
- 201000004193 respiratory failure Diseases 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 238000007632 sclerotherapy Methods 0.000 description 2
- 239000003566 sealing material Substances 0.000 description 2
- 238000002864 sequence alignment Methods 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 235000003702 sterols Nutrition 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 230000002459 sustained effect Effects 0.000 description 2
- 229920001059 synthetic polymer Polymers 0.000 description 2
- 238000007910 systemic administration Methods 0.000 description 2
- 229910052715 tantalum Inorganic materials 0.000 description 2
- GUVRBAGPIYLISA-UHFFFAOYSA-N tantalum atom Chemical compound [Ta] GUVRBAGPIYLISA-UHFFFAOYSA-N 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 2
- 229940071127 thioglycolate Drugs 0.000 description 2
- CWERGRDVMFNCDR-UHFFFAOYSA-M thioglycolate(1-) Chemical compound [O-]C(=O)CS CWERGRDVMFNCDR-UHFFFAOYSA-M 0.000 description 2
- WYWHKKSPHMUBEB-UHFFFAOYSA-N tioguanine Chemical compound N1C(N)=NC(=S)C2=C1N=CN2 WYWHKKSPHMUBEB-UHFFFAOYSA-N 0.000 description 2
- 230000000451 tissue damage Effects 0.000 description 2
- 231100000827 tissue damage Toxicity 0.000 description 2
- 230000026683 transduction Effects 0.000 description 2
- 238000010361 transduction Methods 0.000 description 2
- 238000011830 transgenic mouse model Methods 0.000 description 2
- 230000025033 vasoconstriction Effects 0.000 description 2
- 239000013603 viral vector Substances 0.000 description 2
- 238000001262 western blot Methods 0.000 description 2
- 230000037314 wound repair Effects 0.000 description 2
- CGTADGCBEXYWNE-JUKNQOCSSA-N zotarolimus Chemical compound N1([C@H]2CC[C@@H](C[C@@H](C)[C@H]3OC(=O)[C@@H]4CCCCN4C(=O)C(=O)[C@@]4(O)[C@H](C)CC[C@H](O4)C[C@@H](/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C3)OC)C[C@H]2OC)C=NN=N1 CGTADGCBEXYWNE-JUKNQOCSSA-N 0.000 description 2
- 229950009819 zotarolimus Drugs 0.000 description 2
- WQZGKKKJIJFFOK-SVZMEOIVSA-N (+)-Galactose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-SVZMEOIVSA-N 0.000 description 1
- TVPJXNXJXVKJMU-RRKCRQDMSA-N (2R,3S,5R)-5-(1-chloro-6-iminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-ol Chemical compound ClN1C(C=2N=CN([C@H]3C[C@H](O)[C@@H](CO)O3)C=2N=C1)=N TVPJXNXJXVKJMU-RRKCRQDMSA-N 0.000 description 1
- JSPNNZKWADNWHI-PNANGNLXSA-N (2r)-2-hydroxy-n-[(2s,3r,4e,8e)-3-hydroxy-9-methyl-1-[(2r,3r,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoctadeca-4,8-dien-2-yl]heptadecanamide Chemical compound CCCCCCCCCCCCCCC[C@@H](O)C(=O)N[C@H]([C@H](O)\C=C\CC\C=C(/C)CCCCCCCCC)CO[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O JSPNNZKWADNWHI-PNANGNLXSA-N 0.000 description 1
- OPCHFPHZPIURNA-MFERNQICSA-N (2s)-2,5-bis(3-aminopropylamino)-n-[2-(dioctadecylamino)acetyl]pentanamide Chemical compound CCCCCCCCCCCCCCCCCCN(CC(=O)NC(=O)[C@H](CCCNCCCN)NCCCN)CCCCCCCCCCCCCCCCCC OPCHFPHZPIURNA-MFERNQICSA-N 0.000 description 1
- PUDHBTGHUJUUFI-SCTWWAJVSA-N (4r,7s,10s,13r,16s,19r)-10-(4-aminobutyl)-n-[(2s,3r)-1-amino-3-hydroxy-1-oxobutan-2-yl]-19-[[(2r)-2-amino-3-naphthalen-2-ylpropanoyl]amino]-16-[(4-hydroxyphenyl)methyl]-13-(1h-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-7-propan-2-yl-1,2-dithia-5,8,11,14,17-p Chemical compound C([C@H]1C(=O)N[C@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(N[C@@H](CSSC[C@@H](C(=O)N1)NC(=O)[C@H](N)CC=1C=C2C=CC=CC2=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(N)=O)=O)C(C)C)C1=CC=C(O)C=C1 PUDHBTGHUJUUFI-SCTWWAJVSA-N 0.000 description 1
- FDKXTQMXEQVLRF-ZHACJKMWSA-N (E)-dacarbazine Chemical compound CN(C)\N=N\c1[nH]cnc1C(N)=O FDKXTQMXEQVLRF-ZHACJKMWSA-N 0.000 description 1
- UXDBPOWEWOXJCE-DIPNUNPCSA-N 1,2-dihexadecyl-sn-glycero-3-phosphoethanolamine Chemical compound CCCCCCCCCCCCCCCCOC[C@H](COP(O)(=O)OCCN)OCCCCCCCCCCCCCCCC UXDBPOWEWOXJCE-DIPNUNPCSA-N 0.000 description 1
- MWRBNPKJOOWZPW-NYVOMTAGSA-N 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine zwitterion Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@H](COP(O)(=O)OCCN)OC(=O)CCCCCCC\C=C/CCCCCCCC MWRBNPKJOOWZPW-NYVOMTAGSA-N 0.000 description 1
- NRJAVPSFFCBXDT-HUESYALOSA-N 1,2-distearoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCCCCCCCC NRJAVPSFFCBXDT-HUESYALOSA-N 0.000 description 1
- VSNHCAURESNICA-NJFSPNSNSA-N 1-oxidanylurea Chemical compound N[14C](=O)NO VSNHCAURESNICA-NJFSPNSNSA-N 0.000 description 1
- KSXTUUUQYQYKCR-LQDDAWAPSA-M 2,3-bis[[(z)-octadec-9-enoyl]oxy]propyl-trimethylazanium;chloride Chemical compound [Cl-].CCCCCCCC\C=C/CCCCCCCC(=O)OCC(C[N+](C)(C)C)OC(=O)CCCCCCC\C=C/CCCCCCCC KSXTUUUQYQYKCR-LQDDAWAPSA-M 0.000 description 1
- NRJAVPSFFCBXDT-UHFFFAOYSA-N 2,3-di(octadecanoyloxy)propyl 2-(trimethylazaniumyl)ethyl phosphate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCCCCCCCC NRJAVPSFFCBXDT-UHFFFAOYSA-N 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
- CFWRDBDJAOHXSH-UHFFFAOYSA-N 2-azaniumylethyl 2,3-diacetyloxypropyl phosphate Chemical compound CC(=O)OCC(OC(C)=O)COP(O)(=O)OCCN CFWRDBDJAOHXSH-UHFFFAOYSA-N 0.000 description 1
- AOJJSUZBOXZQNB-VTZDEGQISA-N 4'-epidoxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-VTZDEGQISA-N 0.000 description 1
- NMUSYJAQQFHJEW-KVTDHHQDSA-N 5-azacytidine Chemical compound O=C1N=C(N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 NMUSYJAQQFHJEW-KVTDHHQDSA-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
- 206010000077 Abdominal mass Diseases 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 229910001316 Ag alloy Inorganic materials 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 206010001889 Alveolitis Diseases 0.000 description 1
- 206010073128 Anaplastic oligodendroglioma Diseases 0.000 description 1
- 108020000948 Antisense Oligonucleotides Proteins 0.000 description 1
- 206010003162 Arterial injury Diseases 0.000 description 1
- 206010003210 Arteriosclerosis Diseases 0.000 description 1
- 206010003445 Ascites Diseases 0.000 description 1
- 102000015790 Asparaginase Human genes 0.000 description 1
- 108010024976 Asparaginase Proteins 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 208000008035 Back Pain Diseases 0.000 description 1
- 108010081589 Becaplermin Proteins 0.000 description 1
- 102100036849 C-C motif chemokine 24 Human genes 0.000 description 1
- 102100025248 C-X-C motif chemokine 10 Human genes 0.000 description 1
- 102100036170 C-X-C motif chemokine 9 Human genes 0.000 description 1
- YDNKGFDKKRUKPY-JHOUSYSJSA-N C16 ceramide Natural products CCCCCCCCCCCCCCCC(=O)N[C@@H](CO)[C@H](O)C=CCCCCCCCCCCCCC YDNKGFDKKRUKPY-JHOUSYSJSA-N 0.000 description 1
- 206010006895 Cachexia Diseases 0.000 description 1
- GAGWJHPBXLXJQN-UORFTKCHSA-N Capecitabine Chemical compound C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](C)O1 GAGWJHPBXLXJQN-UORFTKCHSA-N 0.000 description 1
- GAGWJHPBXLXJQN-UHFFFAOYSA-N Capecitabine Natural products C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1C1C(O)C(O)C(C)O1 GAGWJHPBXLXJQN-UHFFFAOYSA-N 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- DLGOEMSEDOSKAD-UHFFFAOYSA-N Carmustine Chemical compound ClCCNC(=O)N(N=O)CCCl DLGOEMSEDOSKAD-UHFFFAOYSA-N 0.000 description 1
- 206010007687 Carotid artery stenosis Diseases 0.000 description 1
- 102000009410 Chemokine receptor Human genes 0.000 description 1
- 108050000299 Chemokine receptor Proteins 0.000 description 1
- 206010008469 Chest discomfort Diseases 0.000 description 1
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 208000032544 Cicatrix Diseases 0.000 description 1
- PTOAARAWEBMLNO-KVQBGUIXSA-N Cladribine Chemical compound C1=NC=2C(N)=NC(Cl)=NC=2N1[C@H]1C[C@H](O)[C@@H](CO)O1 PTOAARAWEBMLNO-KVQBGUIXSA-N 0.000 description 1
- 229910000531 Co alloy Inorganic materials 0.000 description 1
- 102000012422 Collagen Type I Human genes 0.000 description 1
- 108010022452 Collagen Type I Proteins 0.000 description 1
- 102000029816 Collagenase Human genes 0.000 description 1
- 108060005980 Collagenase Proteins 0.000 description 1
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 1
- 208000002330 Congenital Heart Defects Diseases 0.000 description 1
- 208000034656 Contusions Diseases 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 206010011224 Cough Diseases 0.000 description 1
- 108050006400 Cyclin Proteins 0.000 description 1
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 1
- 229930105110 Cyclosporin A Natural products 0.000 description 1
- 108010036949 Cyclosporine Proteins 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 230000008836 DNA modification Effects 0.000 description 1
- 239000003155 DNA primer Substances 0.000 description 1
- 229920004934 Dacron® Polymers 0.000 description 1
- 206010051055 Deep vein thrombosis Diseases 0.000 description 1
- 241000702421 Dependoparvovirus Species 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 208000002251 Dissecting Aneurysm Diseases 0.000 description 1
- 208000001708 Dupuytren contracture Diseases 0.000 description 1
- 208000000059 Dyspnea Diseases 0.000 description 1
- 206010013975 Dyspnoeas Diseases 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 201000009273 Endometriosis Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102400001368 Epidermal growth factor Human genes 0.000 description 1
- 101800003838 Epidermal growth factor Proteins 0.000 description 1
- HTIJFSOGRVMCQR-UHFFFAOYSA-N Epirubicin Natural products COc1cccc2C(=O)c3c(O)c4CC(O)(CC(OC5CC(N)C(=O)C(C)O5)c4c(O)c3C(=O)c12)C(=O)CO HTIJFSOGRVMCQR-UHFFFAOYSA-N 0.000 description 1
- 101710196208 Fibrinolytic enzyme Proteins 0.000 description 1
- 102000003974 Fibroblast growth factor 2 Human genes 0.000 description 1
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 description 1
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
- GYHNNYVSQQEPJS-UHFFFAOYSA-N Gallium Chemical compound [Ga] GYHNNYVSQQEPJS-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 206010064571 Gene mutation Diseases 0.000 description 1
- 208000032612 Glial tumor Diseases 0.000 description 1
- 206010018338 Glioma Diseases 0.000 description 1
- 229930186217 Glycolipid Natural products 0.000 description 1
- 229920002683 Glycosaminoglycan Polymers 0.000 description 1
- 229920000544 Gore-Tex Polymers 0.000 description 1
- 206010019799 Hepatitis viral Diseases 0.000 description 1
- SQUHHTBVTRBESD-UHFFFAOYSA-N Hexa-Ac-myo-Inositol Natural products CC(=O)OC1C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C1OC(C)=O SQUHHTBVTRBESD-UHFFFAOYSA-N 0.000 description 1
- 101000713078 Homo sapiens C-C motif chemokine 24 Proteins 0.000 description 1
- 101000858088 Homo sapiens C-X-C motif chemokine 10 Proteins 0.000 description 1
- 101000947172 Homo sapiens C-X-C motif chemokine 9 Proteins 0.000 description 1
- 101000599951 Homo sapiens Insulin-like growth factor I Proteins 0.000 description 1
- 101100236341 Homo sapiens LYST gene Proteins 0.000 description 1
- 101000917858 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-A Proteins 0.000 description 1
- 101000917839 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-B Proteins 0.000 description 1
- 101000946889 Homo sapiens Monocyte differentiation antigen CD14 Proteins 0.000 description 1
- 101000667110 Homo sapiens Vacuolar protein sorting-associated protein 13B Proteins 0.000 description 1
- 229940122439 Hydroxylase inhibitor Drugs 0.000 description 1
- VSNHCAURESNICA-UHFFFAOYSA-N Hydroxyurea Chemical group NC(=O)NO VSNHCAURESNICA-UHFFFAOYSA-N 0.000 description 1
- 208000031226 Hyperlipidaemia Diseases 0.000 description 1
- 206010010164 Hypertension complications Diseases 0.000 description 1
- 208000003367 Hypopigmentation Diseases 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
- 208000029462 Immunodeficiency disease Diseases 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 1
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 1
- 102100037852 Insulin-like growth factor I Human genes 0.000 description 1
- 102100034343 Integrase Human genes 0.000 description 1
- 206010023126 Jaundice Diseases 0.000 description 1
- 206010023237 Jugular vein thrombosis Diseases 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- GQYIWUVLTXOXAJ-UHFFFAOYSA-N Lomustine Chemical compound ClCCN(N=O)C(=O)NC1CCCCC1 GQYIWUVLTXOXAJ-UHFFFAOYSA-N 0.000 description 1
- 102100029185 Low affinity immunoglobulin gamma Fc region receptor III-B Human genes 0.000 description 1
- 208000019693 Lung disease Diseases 0.000 description 1
- 208000015439 Lysosomal storage disease Diseases 0.000 description 1
- 229940124761 MMP inhibitor Drugs 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 229930192392 Mitomycin Natural products 0.000 description 1
- 208000003250 Mixed connective tissue disease Diseases 0.000 description 1
- HZQDCMWJEBCWBR-UUOKFMHZSA-N Mizoribine Chemical compound OC1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 HZQDCMWJEBCWBR-UUOKFMHZSA-N 0.000 description 1
- ZOKXTWBITQBERF-UHFFFAOYSA-N Molybdenum Chemical compound [Mo] ZOKXTWBITQBERF-UHFFFAOYSA-N 0.000 description 1
- 102000014962 Monocyte Chemoattractant Proteins Human genes 0.000 description 1
- 108010064136 Monocyte Chemoattractant Proteins Proteins 0.000 description 1
- 102100035877 Monocyte differentiation antigen CD14 Human genes 0.000 description 1
- 208000007101 Muscle Cramp Diseases 0.000 description 1
- 101710135898 Myc proto-oncogene protein Proteins 0.000 description 1
- 102100038895 Myc proto-oncogene protein Human genes 0.000 description 1
- QJMCKEPOKRERLN-UHFFFAOYSA-N N-3,4-tridhydroxybenzamide Chemical compound ONC(=O)C1=CC=C(O)C(O)=C1 QJMCKEPOKRERLN-UHFFFAOYSA-N 0.000 description 1
- CRJGESKKUOMBCT-VQTJNVASSA-N N-acetylsphinganine Chemical compound CCCCCCCCCCCCCCC[C@@H](O)[C@H](CO)NC(C)=O CRJGESKKUOMBCT-VQTJNVASSA-N 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 208000009905 Neurofibromatoses Diseases 0.000 description 1
- 229910000990 Ni alloy Inorganic materials 0.000 description 1
- 101710163270 Nuclease Proteins 0.000 description 1
- 208000019462 Occupational injury Diseases 0.000 description 1
- 201000010133 Oligodendroglioma Diseases 0.000 description 1
- 206010053159 Organ failure Diseases 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 101710149632 Pectinesterase A Proteins 0.000 description 1
- 208000000450 Pelvic Pain Diseases 0.000 description 1
- 206010034486 Pericarditis adhesive Diseases 0.000 description 1
- 208000005764 Peripheral Arterial Disease Diseases 0.000 description 1
- 206010057249 Phagocytosis Diseases 0.000 description 1
- 208000013544 Platelet disease Diseases 0.000 description 1
- 108010051742 Platelet-Derived Growth Factor beta Receptor Proteins 0.000 description 1
- 102000018967 Platelet-Derived Growth Factor beta Receptor Human genes 0.000 description 1
- 102100040681 Platelet-derived growth factor C Human genes 0.000 description 1
- 101710170209 Platelet-derived growth factor D Proteins 0.000 description 1
- 102100040682 Platelet-derived growth factor D Human genes 0.000 description 1
- 102100037596 Platelet-derived growth factor subunit A Human genes 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 201000009454 Portal vein thrombosis Diseases 0.000 description 1
- 102000009339 Proliferating Cell Nuclear Antigen Human genes 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 230000007022 RNA scission Effects 0.000 description 1
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 1
- 208000032056 Radiation Fibrosis Syndrome Diseases 0.000 description 1
- 208000035977 Rare disease Diseases 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 102000004278 Receptor Protein-Tyrosine Kinases Human genes 0.000 description 1
- 108090000873 Receptor Protein-Tyrosine Kinases Proteins 0.000 description 1
- 208000035415 Reinfection Diseases 0.000 description 1
- 206010038548 Renal vein thrombosis Diseases 0.000 description 1
- 208000017442 Retinal disease Diseases 0.000 description 1
- 208000014139 Retinal vascular disease Diseases 0.000 description 1
- 206010038923 Retinopathy Diseases 0.000 description 1
- 102000006382 Ribonucleases Human genes 0.000 description 1
- 108010083644 Ribonucleases Proteins 0.000 description 1
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 1
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 1
- 208000028990 Skin injury Diseases 0.000 description 1
- 108091027967 Small hairpin RNA Proteins 0.000 description 1
- 229920002334 Spandex Polymers 0.000 description 1
- 241000251131 Sphyrna Species 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 201000009594 Systemic Scleroderma Diseases 0.000 description 1
- 206010042953 Systemic sclerosis Diseases 0.000 description 1
- 230000024932 T cell mediated immunity Effects 0.000 description 1
- QJJXYPPXXYFBGM-LFZNUXCKSA-N Tacrolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1\C=C(/C)[C@@H]1[C@H](C)[C@@H](O)CC(=O)[C@H](CC=C)/C=C(C)/C[C@H](C)C[C@H](OC)[C@H]([C@H](C[C@H]2C)OC)O[C@@]2(O)C(=O)C(=O)N2CCCC[C@H]2C(=O)O1 QJJXYPPXXYFBGM-LFZNUXCKSA-N 0.000 description 1
- NAVMQTYZDKMPEU-UHFFFAOYSA-N Targretin Chemical compound CC1=CC(C(CCC2(C)C)(C)C)=C2C=C1C(=C)C1=CC=C(C(O)=O)C=C1 NAVMQTYZDKMPEU-UHFFFAOYSA-N 0.000 description 1
- 208000001435 Thromboembolism Diseases 0.000 description 1
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 1
- 101710150448 Transcriptional regulator Myc Proteins 0.000 description 1
- 206010060872 Transplant failure Diseases 0.000 description 1
- 206010045545 Univentricular heart Diseases 0.000 description 1
- 206010046996 Varicose vein Diseases 0.000 description 1
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 1
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 1
- 102100039037 Vascular endothelial growth factor A Human genes 0.000 description 1
- 206010057469 Vascular stenosis 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
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- QCWXUUIWCKQGHC-UHFFFAOYSA-N Zirconium Chemical compound [Zr] QCWXUUIWCKQGHC-UHFFFAOYSA-N 0.000 description 1
- ATBOMIWRCZXYSZ-XZBBILGWSA-N [1-[2,3-dihydroxypropoxy(hydroxy)phosphoryl]oxy-3-hexadecanoyloxypropan-2-yl] (9e,12e)-octadeca-9,12-dienoate Chemical compound CCCCCCCCCCCCCCCC(=O)OCC(COP(O)(=O)OCC(O)CO)OC(=O)CCCCCCC\C=C\C\C=C\CCCCC ATBOMIWRCZXYSZ-XZBBILGWSA-N 0.000 description 1
- NYDLOCKCVISJKK-WRBBJXAJSA-N [3-(dimethylamino)-2-[(z)-octadec-9-enoyl]oxypropyl] (z)-octadec-9-enoate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC(CN(C)C)OC(=O)CCCCCCC\C=C/CCCCCCCC NYDLOCKCVISJKK-WRBBJXAJSA-N 0.000 description 1
- HMNZFMSWFCAGGW-XPWSMXQVSA-N [3-[hydroxy(2-hydroxyethoxy)phosphoryl]oxy-2-[(e)-octadec-9-enoyl]oxypropyl] (e)-octadec-9-enoate Chemical compound CCCCCCCC\C=C\CCCCCCCC(=O)OCC(COP(O)(=O)OCCO)OC(=O)CCCCCCC\C=C\CCCCCCCC HMNZFMSWFCAGGW-XPWSMXQVSA-N 0.000 description 1
- HZEWFHLRYVTOIW-UHFFFAOYSA-N [Ti].[Ni] Chemical compound [Ti].[Ni] HZEWFHLRYVTOIW-UHFFFAOYSA-N 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- 238000002679 ablation Methods 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 231100000439 acute liver injury Toxicity 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 238000012387 aerosolization Methods 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- SHGAZHPCJJPHSC-YCNIQYBTSA-N all-trans-retinoic acid Chemical compound OC(=O)\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-YCNIQYBTSA-N 0.000 description 1
- AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 1
- 229960000473 altretamine Drugs 0.000 description 1
- 229960001220 amsacrine Drugs 0.000 description 1
- XCPGHVQEEXUHNC-UHFFFAOYSA-N amsacrine Chemical compound COC1=CC(NS(C)(=O)=O)=CC=C1NC1=C(C=CC=C2)C2=NC2=CC=CC=C12 XCPGHVQEEXUHNC-UHFFFAOYSA-N 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000003872 anastomosis Effects 0.000 description 1
- 210000003484 anatomy Anatomy 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 229940045799 anthracyclines and related substance Drugs 0.000 description 1
- 230000001567 anti-fibrinolytic effect Effects 0.000 description 1
- 230000002095 anti-migrative effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 239000003080 antimitotic agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 238000013176 antiplatelet therapy Methods 0.000 description 1
- 239000000074 antisense oligonucleotide Substances 0.000 description 1
- 238000012230 antisense oligonucleotides Methods 0.000 description 1
- 239000004019 antithrombin Substances 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 206010002895 aortic dissection Diseases 0.000 description 1
- 230000001640 apoptogenic effect Effects 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 230000004596 appetite loss Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 239000008135 aqueous vehicle Substances 0.000 description 1
- 229960003856 argatroban Drugs 0.000 description 1
- KXNPVXPOPUZYGB-XYVMCAHJSA-N argatroban Chemical compound OC(=O)[C@H]1C[C@H](C)CCN1C(=O)[C@H](CCCN=C(N)N)NS(=O)(=O)C1=CC=CC2=C1NC[C@H](C)C2 KXNPVXPOPUZYGB-XYVMCAHJSA-N 0.000 description 1
- 208000011775 arteriosclerosis disease Diseases 0.000 description 1
- 206010003230 arteritis Diseases 0.000 description 1
- 208000028922 artery disease Diseases 0.000 description 1
- 239000002473 artificial blood Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960003272 asparaginase Drugs 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-M asparaginate Chemical compound [O-]C(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-M 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000003305 autocrine Effects 0.000 description 1
- 229960002756 azacitidine Drugs 0.000 description 1
- VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 description 1
- 229960002170 azathioprine Drugs 0.000 description 1
- LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- XFILPEOLDIKJHX-QYZOEREBSA-N batimastat Chemical compound C([C@@H](C(=O)NC)NC(=O)[C@H](CC(C)C)[C@H](CSC=1SC=CC=1)C(=O)NO)C1=CC=CC=C1 XFILPEOLDIKJHX-QYZOEREBSA-N 0.000 description 1
- 229950001858 batimastat Drugs 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- 229960000397 bevacizumab Drugs 0.000 description 1
- 229960002938 bexarotene Drugs 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 108010055460 bivalirudin Proteins 0.000 description 1
- OIRCOABEOLEUMC-GEJPAHFPSA-N bivalirudin Chemical compound C([C@@H](C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)CNC(=O)CNC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 OIRCOABEOLEUMC-GEJPAHFPSA-N 0.000 description 1
- 229960001500 bivalirudin Drugs 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 230000023555 blood coagulation Effects 0.000 description 1
- 238000010322 bone marrow transplantation Methods 0.000 description 1
- 239000007975 buffered saline Substances 0.000 description 1
- 239000004067 bulking agent Substances 0.000 description 1
- 229960004117 capecitabine Drugs 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000000837 carbohydrate group Chemical group 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 229960004562 carboplatin Drugs 0.000 description 1
- 229960005243 carmustine Drugs 0.000 description 1
- 208000006170 carotid stenosis Diseases 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 201000007262 cavernous sinus thrombosis Diseases 0.000 description 1
- 229960000590 celecoxib Drugs 0.000 description 1
- RZEKVGVHFLEQIL-UHFFFAOYSA-N celecoxib Chemical compound C1=CC(C)=CC=C1C1=CC(C(F)(F)F)=NN1C1=CC=C(S(N)(=O)=O)C=C1 RZEKVGVHFLEQIL-UHFFFAOYSA-N 0.000 description 1
- 230000034196 cell chemotaxis Effects 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 239000002771 cell marker Substances 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000007248 cellular mechanism Effects 0.000 description 1
- 230000005754 cellular signaling Effects 0.000 description 1
- 229940106189 ceramide Drugs 0.000 description 1
- ZVEQCJWYRWKARO-UHFFFAOYSA-N ceramide Natural products CCCCCCCCCCCCCCC(O)C(=O)NC(CO)C(O)C=CCCC=C(C)CCCCCCCCC ZVEQCJWYRWKARO-UHFFFAOYSA-N 0.000 description 1
- 210000001627 cerebral artery Anatomy 0.000 description 1
- 229930183167 cerebroside Natural products 0.000 description 1
- RIZIAUKTHDLMQX-UHFFFAOYSA-N cerebroside D Natural products CCCCCCCCCCCCCCCCC(O)C(=O)NC(C(O)C=CCCC=C(C)CCCCCCCCC)COC1OC(CO)C(O)C(O)C1O RIZIAUKTHDLMQX-UHFFFAOYSA-N 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 229960004630 chlorambucil Drugs 0.000 description 1
- JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 description 1
- 229910052804 chromium Inorganic materials 0.000 description 1
- 239000011651 chromium Substances 0.000 description 1
- SZMZREIADCOWQA-UHFFFAOYSA-N chromium cobalt nickel Chemical compound [Cr].[Co].[Ni] SZMZREIADCOWQA-UHFFFAOYSA-N 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 230000009693 chronic damage Effects 0.000 description 1
- 230000007881 chronic fibrosis Effects 0.000 description 1
- 230000006020 chronic inflammation Effects 0.000 description 1
- 208000037893 chronic inflammatory disorder Diseases 0.000 description 1
- 229960001265 ciclosporin Drugs 0.000 description 1
- 229960004316 cisplatin Drugs 0.000 description 1
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
- 210000003690 classically activated macrophage Anatomy 0.000 description 1
- 239000011247 coating layer Substances 0.000 description 1
- 229910017052 cobalt Inorganic materials 0.000 description 1
- 239000010941 cobalt Substances 0.000 description 1
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 1
- 229960002424 collagenase Drugs 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 230000004540 complement-dependent cytotoxicity Effects 0.000 description 1
- 208000028831 congenital heart disease Diseases 0.000 description 1
- 208000018631 connective tissue disease Diseases 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 239000002285 corn oil Substances 0.000 description 1
- 235000005687 corn oil Nutrition 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 229960004397 cyclophosphamide Drugs 0.000 description 1
- 229930182912 cyclosporin Natural products 0.000 description 1
- 229940104302 cytosine Drugs 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 229960003901 dacarbazine Drugs 0.000 description 1
- 229960000975 daunorubicin Drugs 0.000 description 1
- STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 230000000593 degrading effect Effects 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 229960002923 denileukin diftitox Drugs 0.000 description 1
- 108010017271 denileukin diftitox Proteins 0.000 description 1
- CFCUWKMKBJTWLW-UHFFFAOYSA-N deoliosyl-3C-alpha-L-digitoxosyl-MTM Natural products CC=1C(O)=C2C(O)=C3C(=O)C(OC4OC(C)C(O)C(OC5OC(C)C(O)C(OC6OC(C)C(O)C(C)(O)C6)C5)C4)C(C(OC)C(=O)C(O)C(C)O)CC3=CC2=CC=1OC(OC(C)C1O)CC1OC1CC(O)C(O)C(C)O1 CFCUWKMKBJTWLW-UHFFFAOYSA-N 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 230000003831 deregulation Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 201000009101 diabetic angiopathy Diseases 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 230000010339 dilation Effects 0.000 description 1
- 238000006471 dimerization reaction Methods 0.000 description 1
- MCWXGJITAZMZEV-UHFFFAOYSA-N dimethoate Chemical compound CNC(=O)CSP(=S)(OC)OC MCWXGJITAZMZEV-UHFFFAOYSA-N 0.000 description 1
- PSLWZOIUBRXAQW-UHFFFAOYSA-M dimethyl(dioctadecyl)azanium;bromide Chemical compound [Br-].CCCCCCCCCCCCCCCCCC[N+](C)(C)CCCCCCCCCCCCCCCCCC PSLWZOIUBRXAQW-UHFFFAOYSA-M 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 229960003668 docetaxel Drugs 0.000 description 1
- 230000007783 downstream signaling Effects 0.000 description 1
- 208000017574 dry cough Diseases 0.000 description 1
- 210000001951 dura mater Anatomy 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 229910000701 elgiloys (Co-Cr-Ni Alloy) Inorganic materials 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 230000008290 endocytic mechanism Effects 0.000 description 1
- 239000006274 endogenous ligand Substances 0.000 description 1
- 210000001163 endosome Anatomy 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 230000006862 enzymatic digestion Effects 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 210000003979 eosinophil Anatomy 0.000 description 1
- 229940116977 epidermal growth factor Drugs 0.000 description 1
- 229960001904 epirubicin Drugs 0.000 description 1
- 229960001842 estramustine Drugs 0.000 description 1
- FRPJXPJMRWBBIH-RBRWEJTLSA-N estramustine Chemical compound ClCCN(CCCl)C(=O)OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 FRPJXPJMRWBBIH-RBRWEJTLSA-N 0.000 description 1
- CEIPQQODRKXDSB-UHFFFAOYSA-N ethyl 3-(6-hydroxynaphthalen-2-yl)-1H-indazole-5-carboximidate dihydrochloride Chemical compound Cl.Cl.C1=C(O)C=CC2=CC(C3=NNC4=CC=C(C=C43)C(=N)OCC)=CC=C21 CEIPQQODRKXDSB-UHFFFAOYSA-N 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 229960005420 etoposide Drugs 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
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 201000001155 extrinsic allergic alveolitis Diseases 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 230000019305 fibroblast migration Effects 0.000 description 1
- 208000036449 fibrotic liver disease Diseases 0.000 description 1
- 239000010408 film Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 229960000390 fludarabine Drugs 0.000 description 1
- GIUYCYHIANZCFB-FJFJXFQQSA-N fludarabine phosphate Chemical compound C1=NC=2C(N)=NC(F)=NC=2N1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@@H]1O GIUYCYHIANZCFB-FJFJXFQQSA-N 0.000 description 1
- 229960002949 fluorouracil Drugs 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 231100000221 frame shift mutation induction Toxicity 0.000 description 1
- 230000037433 frameshift Effects 0.000 description 1
- 230000005714 functional activity Effects 0.000 description 1
- 229910052733 gallium Inorganic materials 0.000 description 1
- 150000002270 gangliosides Chemical class 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 229960005277 gemcitabine Drugs 0.000 description 1
- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 description 1
- 229960000578 gemtuzumab Drugs 0.000 description 1
- 102000034356 gene-regulatory proteins Human genes 0.000 description 1
- 108091006104 gene-regulatory proteins Proteins 0.000 description 1
- 208000005017 glioblastoma Diseases 0.000 description 1
- 229930182478 glucoside Natural products 0.000 description 1
- 150000008131 glucosides Chemical class 0.000 description 1
- 125000003827 glycol group Chemical group 0.000 description 1
- 150000002339 glycosphingolipids Chemical class 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- LVASCWIMLIKXLA-LSDHHAIUSA-N halofuginone Chemical compound O[C@@H]1CCCN[C@H]1CC(=O)CN1C(=O)C2=CC(Cl)=C(Br)C=C2N=C1 LVASCWIMLIKXLA-LSDHHAIUSA-N 0.000 description 1
- 229950010152 halofuginone Drugs 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000002008 hemorrhagic effect Effects 0.000 description 1
- 231100000234 hepatic damage Toxicity 0.000 description 1
- 231100000753 hepatic injury Toxicity 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- UUVWYPNAQBNQJQ-UHFFFAOYSA-N hexamethylmelamine Chemical compound CN(C)C1=NC(N(C)C)=NC(N(C)C)=N1 UUVWYPNAQBNQJQ-UHFFFAOYSA-N 0.000 description 1
- 229940006607 hirudin Drugs 0.000 description 1
- 238000010562 histological examination Methods 0.000 description 1
- 238000009396 hybridization Methods 0.000 description 1
- 210000004408 hybridoma Anatomy 0.000 description 1
- 229960001330 hydroxycarbamide Drugs 0.000 description 1
- 230000002390 hyperplastic effect Effects 0.000 description 1
- 230000003463 hyperproliferative effect Effects 0.000 description 1
- 208000022098 hypersensitivity pneumonitis Diseases 0.000 description 1
- 230000003425 hypopigmentation Effects 0.000 description 1
- 229960000908 idarubicin Drugs 0.000 description 1
- 229960001101 ifosfamide Drugs 0.000 description 1
- HOMGKSMUEGBAAB-UHFFFAOYSA-N ifosfamide Chemical compound ClCCNP1(=O)OCCCN1CCCl HOMGKSMUEGBAAB-UHFFFAOYSA-N 0.000 description 1
- 210000003090 iliac artery Anatomy 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 239000012729 immediate-release (IR) formulation Substances 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000036737 immune function Effects 0.000 description 1
- 208000026278 immune system disease Diseases 0.000 description 1
- 230000007813 immunodeficiency Effects 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 230000001506 immunosuppresive effect Effects 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 229910052738 indium Inorganic materials 0.000 description 1
- APFVFJFRJDLVQX-UHFFFAOYSA-N indium atom Chemical compound [In] APFVFJFRJDLVQX-UHFFFAOYSA-N 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000004941 influx Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 238000002664 inhalation therapy Methods 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- CDAISMWEOUEBRE-GPIVLXJGSA-N inositol Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](O)[C@@H]1O CDAISMWEOUEBRE-GPIVLXJGSA-N 0.000 description 1
- 229960000367 inositol Drugs 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 108010042414 interferon gamma-1b Proteins 0.000 description 1
- 229940028862 interferon gamma-1b Drugs 0.000 description 1
- 238000013152 interventional procedure Methods 0.000 description 1
- 230000029225 intracellular protein transport Effects 0.000 description 1
- 230000010189 intracellular transport Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 229910052741 iridium Inorganic materials 0.000 description 1
- GKOZUEZYRPOHIO-UHFFFAOYSA-N iridium atom Chemical compound [Ir] GKOZUEZYRPOHIO-UHFFFAOYSA-N 0.000 description 1
- UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 description 1
- 229960004768 irinotecan Drugs 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 208000011379 keloid formation Diseases 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229960002437 lanreotide Drugs 0.000 description 1
- 108010021336 lanreotide Proteins 0.000 description 1
- 150000002605 large molecules Chemical class 0.000 description 1
- 238000013532 laser treatment Methods 0.000 description 1
- 229960000681 leflunomide Drugs 0.000 description 1
- VHOGYURTWQBHIL-UHFFFAOYSA-N leflunomide Chemical compound O1N=CC(C(=O)NC=2C=CC(=CC=2)C(F)(F)F)=C1C VHOGYURTWQBHIL-UHFFFAOYSA-N 0.000 description 1
- 231100000225 lethality Toxicity 0.000 description 1
- 230000023404 leukocyte cell-cell adhesion Effects 0.000 description 1
- 201000002818 limb ischemia Diseases 0.000 description 1
- 201000007270 liver cancer Diseases 0.000 description 1
- 230000008818 liver damage Effects 0.000 description 1
- 230000003908 liver function Effects 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 210000005228 liver tissue Anatomy 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 229960002247 lomustine Drugs 0.000 description 1
- 208000019017 loss of appetite Diseases 0.000 description 1
- 235000021266 loss of appetite Nutrition 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 239000003055 low molecular weight heparin Substances 0.000 description 1
- 229940127215 low-molecular weight heparin Drugs 0.000 description 1
- 230000001926 lymphatic effect Effects 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 230000036244 malformation Effects 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 210000001349 mammary artery Anatomy 0.000 description 1
- WPBNNNQJVZRUHP-UHFFFAOYSA-L manganese(2+);methyl n-[[2-(methoxycarbonylcarbamothioylamino)phenyl]carbamothioyl]carbamate;n-[2-(sulfidocarbothioylamino)ethyl]carbamodithioate Chemical compound [Mn+2].[S-]C(=S)NCCNC([S-])=S.COC(=O)NC(=S)NC1=CC=CC=C1NC(=S)NC(=O)OC WPBNNNQJVZRUHP-UHFFFAOYSA-L 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 229960004961 mechlorethamine Drugs 0.000 description 1
- HAWPXGHAZFHHAD-UHFFFAOYSA-N mechlorethamine Chemical compound ClCCN(C)CCCl HAWPXGHAZFHHAD-UHFFFAOYSA-N 0.000 description 1
- 229960001924 melphalan Drugs 0.000 description 1
- SGDBTWWWUNNDEQ-LBPRGKRZSA-N melphalan Chemical compound OC(=O)[C@@H](N)CC1=CC=C(N(CCCl)CCCl)C=C1 SGDBTWWWUNNDEQ-LBPRGKRZSA-N 0.000 description 1
- 229960001428 mercaptopurine Drugs 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 description 1
- HPNSFSBZBAHARI-UHFFFAOYSA-N micophenolic acid Natural products OC1=C(CC=C(C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-UHFFFAOYSA-N 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 238000002324 minimally invasive surgery Methods 0.000 description 1
- 239000003595 mist 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
- 239000003226 mitogen Substances 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
- 229950000844 mizoribine Drugs 0.000 description 1
- 238000007479 molecular analysis Methods 0.000 description 1
- 230000009456 molecular mechanism Effects 0.000 description 1
- 229910052750 molybdenum Inorganic materials 0.000 description 1
- 239000011733 molybdenum Substances 0.000 description 1
- 210000005087 mononuclear cell Anatomy 0.000 description 1
- 210000002464 muscle smooth vascular Anatomy 0.000 description 1
- 229960000951 mycophenolic acid Drugs 0.000 description 1
- HPNSFSBZBAHARI-RUDMXATFSA-N mycophenolic acid Chemical compound OC1=C(C\C=C(/C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-RUDMXATFSA-N 0.000 description 1
- 206010028537 myelofibrosis Diseases 0.000 description 1
- ZLDPNFYTUDQDMJ-UHFFFAOYSA-N n-octadecyloctadecan-1-amine;hydrobromide Chemical compound Br.CCCCCCCCCCCCCCCCCCNCCCCCCCCCCCCCCCCCC ZLDPNFYTUDQDMJ-UHFFFAOYSA-N 0.000 description 1
- 210000003928 nasal cavity Anatomy 0.000 description 1
- 229920005615 natural polymer Polymers 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 230000001338 necrotic effect Effects 0.000 description 1
- 201000009925 nephrosclerosis Diseases 0.000 description 1
- 201000004931 neurofibromatosis Diseases 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- VVGIYYKRAMHVLU-UHFFFAOYSA-N newbouldiamide Natural products CCCCCCCCCCCCCCCCCCCC(O)C(O)C(O)C(CO)NC(=O)CCCCCCCCCCCCCCCCC VVGIYYKRAMHVLU-UHFFFAOYSA-N 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- HLXZNVUGXRDIFK-UHFFFAOYSA-N nickel titanium Chemical compound [Ti].[Ti].[Ti].[Ti].[Ti].[Ti].[Ti].[Ti].[Ti].[Ti].[Ti].[Ni].[Ni].[Ni].[Ni].[Ni].[Ni].[Ni].[Ni].[Ni].[Ni].[Ni].[Ni].[Ni].[Ni] HLXZNVUGXRDIFK-UHFFFAOYSA-N 0.000 description 1
- 230000000414 obstructive effect Effects 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 238000006384 oligomerization reaction Methods 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 230000004768 organ dysfunction Effects 0.000 description 1
- 150000002895 organic esters Chemical class 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 229960001756 oxaliplatin Drugs 0.000 description 1
- DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical compound O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- SWELZOZIOHGSPA-UHFFFAOYSA-N palladium silver Chemical compound [Pd].[Ag] SWELZOZIOHGSPA-UHFFFAOYSA-N 0.000 description 1
- 210000004738 parenchymal cell Anatomy 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000009518 penetrating injury Effects 0.000 description 1
- 229960002340 pentostatin Drugs 0.000 description 1
- FPVKHBSQESCIEP-JQCXWYLXSA-N pentostatin Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(N=CNC[C@H]2O)=C2N=C1 FPVKHBSQESCIEP-JQCXWYLXSA-N 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 238000007888 peripheral angioplasty Methods 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 230000003836 peripheral circulation Effects 0.000 description 1
- 210000003200 peritoneal cavity Anatomy 0.000 description 1
- 210000004303 peritoneum Anatomy 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 230000008782 phagocytosis Effects 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 125000001095 phosphatidyl group Chemical group 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 230000006461 physiological response Effects 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229960003171 plicamycin Drugs 0.000 description 1
- 230000010287 polarization Effects 0.000 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 229920000139 polyethylene terephthalate Polymers 0.000 description 1
- 239000005020 polyethylene terephthalate Substances 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229940068977 polysorbate 20 Drugs 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 229920002635 polyurethane Polymers 0.000 description 1
- 239000004814 polyurethane Substances 0.000 description 1
- 230000030786 positive chemotaxis Effects 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- FYPMFJGVHOHGLL-UHFFFAOYSA-N probucol Chemical compound C=1C(C(C)(C)C)=C(O)C(C(C)(C)C)=CC=1SC(C)(C)SC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 FYPMFJGVHOHGLL-UHFFFAOYSA-N 0.000 description 1
- 229960003912 probucol Drugs 0.000 description 1
- 229960000624 procarbazine Drugs 0.000 description 1
- CPTBDICYNRMXFX-UHFFFAOYSA-N procarbazine Chemical compound CNNCC1=CC=C(C(=O)NC(C)C)C=C1 CPTBDICYNRMXFX-UHFFFAOYSA-N 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 230000009696 proliferative response Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 239000001294 propane Substances 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 108020001580 protein domains Proteins 0.000 description 1
- 230000004853 protein function Effects 0.000 description 1
- 230000006916 protein interaction Effects 0.000 description 1
- 230000004850 protein–protein interaction Effects 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 210000001147 pulmonary artery Anatomy 0.000 description 1
- 208000002815 pulmonary hypertension Diseases 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 229920013730 reactive polymer Polymers 0.000 description 1
- 238000007890 renal artery angioplasty Methods 0.000 description 1
- 230000003252 repetitive effect Effects 0.000 description 1
- 238000002271 resection Methods 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 230000004202 respiratory function Effects 0.000 description 1
- 230000008458 response to injury Effects 0.000 description 1
- 230000004043 responsiveness Effects 0.000 description 1
- 230000000284 resting effect Effects 0.000 description 1
- 230000000250 revascularization Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 229910052707 ruthenium Inorganic materials 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 230000037387 scars Effects 0.000 description 1
- CDAISMWEOUEBRE-UHFFFAOYSA-N scyllo-inosotol Natural products OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 229910001285 shape-memory alloy Inorganic materials 0.000 description 1
- 208000013220 shortness of breath Diseases 0.000 description 1
- 230000003584 silencer Effects 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 201000004477 skin sarcoma Diseases 0.000 description 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
- 229940001584 sodium metabisulfite Drugs 0.000 description 1
- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
- 238000000935 solvent evaporation Methods 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 239000004759 spandex Substances 0.000 description 1
- 150000003408 sphingolipids Chemical class 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 210000004500 stellate cell Anatomy 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 239000003206 sterilizing agent Substances 0.000 description 1
- 150000003432 sterols Chemical class 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 230000003874 surgical anastomosis Effects 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229960001967 tacrolimus Drugs 0.000 description 1
- QJJXYPPXXYFBGM-SHYZHZOCSA-N tacrolimus Natural products CO[C@H]1C[C@H](CC[C@@H]1O)C=C(C)[C@H]2OC(=O)[C@H]3CCCCN3C(=O)C(=O)[C@@]4(O)O[C@@H]([C@H](C[C@H]4C)OC)[C@@H](C[C@H](C)CC(=C[C@@H](CC=C)C(=O)C[C@H](O)[C@H]2C)C)OC QJJXYPPXXYFBGM-SHYZHZOCSA-N 0.000 description 1
- 229940063683 taxotere Drugs 0.000 description 1
- 210000002435 tendon Anatomy 0.000 description 1
- 229960001278 teniposide Drugs 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
- TXEYQDLBPFQVAA-UHFFFAOYSA-N tetrafluoromethane Chemical compound FC(F)(F)F TXEYQDLBPFQVAA-UHFFFAOYSA-N 0.000 description 1
- 229960000278 theophylline Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 239000010409 thin film Substances 0.000 description 1
- 210000000115 thoracic cavity Anatomy 0.000 description 1
- 238000013151 thrombectomy Methods 0.000 description 1
- 210000001541 thymus gland Anatomy 0.000 description 1
- 108010065972 tick anticoagulant peptide Proteins 0.000 description 1
- 229910052718 tin Inorganic materials 0.000 description 1
- 239000011135 tin Substances 0.000 description 1
- 229960003087 tioguanine Drugs 0.000 description 1
- 230000025366 tissue development Effects 0.000 description 1
- 230000008467 tissue growth Effects 0.000 description 1
- 229910052719 titanium Inorganic materials 0.000 description 1
- 239000010936 titanium Substances 0.000 description 1
- 238000011200 topical administration Methods 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
- 229960000303 topotecan Drugs 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
- 229960005342 tranilast Drugs 0.000 description 1
- NZHGWWWHIYHZNX-CSKARUKUSA-N tranilast Chemical compound C1=C(OC)C(OC)=CC=C1\C=C\C(=O)NC1=CC=CC=C1C(O)=O NZHGWWWHIYHZNX-CSKARUKUSA-N 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 229960001727 tretinoin Drugs 0.000 description 1
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical class CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 1
- 230000005748 tumor development Effects 0.000 description 1
- WFKWXMTUELFFGS-UHFFFAOYSA-N tungsten Chemical compound [W] WFKWXMTUELFFGS-UHFFFAOYSA-N 0.000 description 1
- 229910052721 tungsten Inorganic materials 0.000 description 1
- 239000010937 tungsten Substances 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 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 1
- 238000002255 vaccination Methods 0.000 description 1
- 229910052720 vanadium Inorganic materials 0.000 description 1
- GPPXJZIENCGNKB-UHFFFAOYSA-N vanadium Chemical compound [V]#[V] GPPXJZIENCGNKB-UHFFFAOYSA-N 0.000 description 1
- 208000027185 varicose disease Diseases 0.000 description 1
- 210000005167 vascular cell Anatomy 0.000 description 1
- 208000019553 vascular disease Diseases 0.000 description 1
- 230000024883 vasodilation Effects 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 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
- GBABOYUKABKIAF-GHYRFKGUSA-N vinorelbine Chemical compound C1N(CC=2C3=CC=CC=C3NC=22)CC(CC)=C[C@H]1C[C@]2(C(=O)OC)C1=CC([C@]23[C@H]([C@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC GBABOYUKABKIAF-GHYRFKGUSA-N 0.000 description 1
- 229960002066 vinorelbine Drugs 0.000 description 1
- 201000001862 viral hepatitis Diseases 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 208000016261 weight loss Diseases 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052726 zirconium Inorganic materials 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- 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
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
- A61B17/34—Trocars; Puncturing needles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
- A61F2/04—Hollow or tubular parts of organs, e.g. bladders, tracheae, bronchi or bile ducts
- A61F2/06—Blood vessels
- A61F2/07—Stent-grafts
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4704—2-Quinolinones, e.g. carbostyril
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
- A61K31/7105—Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
- A61K31/713—Double-stranded nucleic acids or oligonucleotides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
-
- 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
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/507—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials for artificial blood vessels
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/54—Biologically active materials, e.g. therapeutic substances
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
- A61L29/14—Materials characterised by their function or physical properties, e.g. lubricating compositions
- A61L29/16—Biologically active materials, e.g. therapeutic substances
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L31/16—Biologically active materials, e.g. therapeutic substances
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L33/00—Antithrombogenic treatment of surgical articles, e.g. sutures, catheters, prostheses, or of articles for the manipulation or conditioning of blood; Materials for such treatment
- A61L33/06—Use of macromolecular materials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M25/00—Catheters; Hollow probes
- A61M25/10—Balloon catheters
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
- A61M5/178—Syringes
- A61M5/31—Details
- A61M5/32—Needles; Details of needles pertaining to their connection with syringe or hub; Accessories for bringing the needle into, or holding the needle on, the body; Devices for protection of needles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- 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
-
- 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
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
-
- 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
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
- A61L2300/252—Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
- A61L2300/256—Antibodies, e.g. immunoglobulins, vaccines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
- A61L2300/258—Genetic materials, DNA, RNA, genes, vectors, e.g. plasmids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/41—Anti-inflammatory agents, e.g. NSAIDs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/42—Anti-thrombotic agents, anticoagulants, anti-platelet agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
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)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Molecular Biology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biomedical Technology (AREA)
- General Chemical & Material Sciences (AREA)
- Dermatology (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Transplantation (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Immunology (AREA)
- Biochemistry (AREA)
- Surgery (AREA)
- Hematology (AREA)
- Cardiology (AREA)
- Pulmonology (AREA)
- Urology & Nephrology (AREA)
- Mycology (AREA)
- Microbiology (AREA)
- Anesthesiology (AREA)
- Diabetes (AREA)
- Gastroenterology & Hepatology (AREA)
- Biophysics (AREA)
- Botany (AREA)
- Pathology (AREA)
- Medical Informatics (AREA)
- Child & Adolescent Psychology (AREA)
Description
テキストファイルとして2015年5月4日に提出され、「NWCH100 PCT_ST25.txt」という名前で、2015年5月1日に作成され、51,000倍とのサイズを有する配列表は、参照によって本明細書に組み込まれる。
本発明は、米国国立衛生研究所によりChristopher Breuerに授与されたNIH助成金R01 HL098228の下で政府支援によりなされた。政府は本発明の特定の権利を有する。
本発明の分野は、一般に、血管組織再生の増強、ならびに新生内膜過形成および線維増殖性疾患に関連する罹患率および死亡率の軽減のための組成物、デバイス、および方法に関する。
組織修復は、傷害部位の局所炎症促進性細胞由来の刺激性サイトカインシグナル伝達に応答して死細胞または損傷細胞の順序付けた除去および置き換えを容易にする複雑な段階的過程である(Wynn and Baron,Semin Liver Dis.,30(3):245−257(2010);Wynn,Clin.Invest.117:524−529(2007))。しかし、組織修復応答が不適切であるか、例えば、慢性疾患または傷害の繰返しに応答して長期間持続される場合、正常な再生機構が傷害部位での過剰な新組織(neotissue)成長および細胞外基質(ECM)成分の蓄積に起因する病的状況を生じさせ得る。
本発明のさらなる目的は、被験体において治癒を促進し、瘢痕形成、癒着、および線維増殖性疾患を阻害するための組成物、方法、およびデバイスを提供することである。
リソソーム輸送制御因子(「LYST」)タンパク質の阻害が組織損傷部位の炎症応答の軽減に関連することを明らかにした。LYSTタンパク質の発現および機能の阻害のための組成物および方法を記載する。組成物および方法は、再生促進性免疫応答を生じるマクロファージ、血小板、およびナチュラルキラー細胞の機能を変更することによる、新生内膜の形成および線維増殖性障害に寄与する免疫過程の調整に有用であり得る。
本発明は、例えば、以下の項目も提供する。
(項目1)
a)被験体における(in a subject in a subject)マクロファージ浸潤の軽減もしくは防止または血小板活性化の軽減もしくは防止に有効な量の1つまたはそれを超えるLYSTのインヒビター;および
b)生理学的に許容され得るキャリア
を含み、
1つまたはそれを超えるLYSTのインヒビターの該量が該被験体における血管新組織の形成を防止しない、薬学的組成物。
(項目2)
0.1mg/kgヒト体重と1000mg/kgヒト体重との間の量の1つまたはそれを超えるLYSTインヒビターを送達する投薬製剤中の項目1に記載の組成物。
(項目3)
マクロファージ浸潤を軽減または防止するのに有効な投薬量の項目1に記載の組成物。
(項目4)
血小板活性化を軽減または防止するのに有効な投薬量の項目1に記載の組成物。
(項目5)
1つまたはそれを超えるLYSTインヒビターが、抗LYST抗体の結合特異性を有する抗体、抗体フラグメント、またはタンパク質である、項目1に記載の組成物。
(項目6)
1つまたはそれを超えるLYSTインヒビターが、アンチセンス分子、siRNA、miRNA、アプタマー、リボザイム、三重鎖形成分子、RNAi、および外部ガイド配列からなる群から選択される機能的核酸である、項目1に記載の組成物。
(項目7)
1つまたはそれを超える機能的核酸が発現ベクターから発現される、項目6に記載の組成物。
(項目8)
ナノ粒子、微粒子、ミセル、エマルジョン、合成リポタンパク質粒子、リポソーム、カーボンナノチューブ、ゲル、またはコーティングからなる群から選択される送達ビヒクルをさらに含む、項目1に記載の組成物。
(項目9)
他の抗新生内膜剤、化学療法剤、ステロイド性および非ステロイド性の抗炎症薬、従来の免疫治療剤、免疫抑制剤、サイトカイン、ケモカイン、および成長因子からなる群から選択される1つまたはそれを超えるさらなる治療剤をさらに含む、項目1に記載の組成物。
(項目10)
項目1〜9のいずれか1項に記載の組成物を含む血管グラフトまたは医療デバイス。
(項目11)
前記組成物が前記グラフトまたはデバイス上にコーティングされているか、該グラフトまたはデバイス内に組み込まれている、項目10に記載の血管グラフトまたは医療デバイス。
(項目12)
前記デバイスが、ステント、植込物、針、カニューレ、カテーテル、シャント、バルーン、および弁からなる群から選択される、項目11に記載の医療デバイス。
(項目13)
前記デバイスがステントである、項目12に記載の医療デバイス。
(項目14)
前記ステントが、前記組成物を溶出する薬剤溶出性ステントである、項目13に記載の医療デバイス。
(項目15)
前記グラフトが、自己グラフト、保存自己グラフト、同種異系グラフト、異種グラフト、または合成グラフトである、項目10に記載の血管グラフト。
(項目16)
被験体において瘢痕形成または狭窄を生じさせ得るマクロファージ浸潤を軽減または防止する方法であって、それを必要とする被験体に項目1または3〜9のいずれか1項に記載の組成物または項目10〜15のいずれか1項に記載のデバイスを投与することを含む、方法。
(項目17)
被験体において動脈血栓症または静脈血栓症を生じさせ得る血小板活性化を軽減または防止する方法であって、それを必要とする被験体に項目1〜9のいずれか1項に記載の組成物または項目10〜15のいずれか1項に記載のデバイスを投与することを含む、方法。
(項目18)
前記被験体が、再狭窄または他の血管増殖障害のリスクが有るか、再狭窄または他の血管増殖障害を有する、項目16または17に記載の方法。
(項目19)
前記被験体は、血管外傷、血管形成術、血管手術、または移植動脈症を経験していたか、経験しているか、経験する、項目16または17に記載の方法。
(項目20)
前記組成物またはデバイスを、非処置コントロール被験体と比較して、被験体における瘢痕組織の形成の軽減または防止、治癒の促進、肥厚性瘢痕化、ケロイド、または癒着の発症の軽減または防止、肝臓の線維症、肺の線維症、心臓の線維症、または腎臓の線維症の軽減または防止、新生内膜形成、狭窄、または再狭窄の軽減または防止、血栓症の軽減または防止、またはその任意の組み合わせのために使用する、項目16または17に記載の方法。
(項目21)
瘢痕組織の形成の軽減または防止により、ペースメーカー、神経刺激器、置換心臓弁、および人工関節からなる群から選択される1つまたはそれを超えるバイオプロテーゼデバイスの組み込みを促進するが、被包を遮断する、項目16に記載の方法。
(項目22)
瘢痕組織の形成の軽減または防止が、非処置コントロール被験体と比較して、被験体における血管植込物の植込の部位、血管傷害の部位、または手術の部位での新生内膜形成の処置または防止に有効である、項目16に記載の方法。
(項目23)
前記組成物またはデバイスを、非処置コントロール被験体と比較して、被験体における血小板由来成長因子、トランスフォーミング成長因子β、またはその任意の組み合わせの発現を軽減または防止するために使用する、項目17に記載の方法。
(項目24)
血管グラフトの狭窄または再狭窄を軽減する方法であって、被験体への該グラフトの植込前に項目1〜10のいずれか1項に記載の組成物で該グラフトをex vivoにて処置することを含む、方法。
I.定義
用語「狭窄」は、血管壁(内皮)傷害後に生じる血管の異常な狭小化をいう。いくつかの実施形態では、狭窄は、50%またはそれを超える管腔外周の減少を含む。用語「再狭窄」は、既存の狭窄部位の狭窄または介入手順使用後の血管の管腔もしくは合成グラフトの狭小化をいう。再狭窄は、本明細書中で使用する場合、閉塞を含む。狭窄または再狭窄に至る例示的な傷害には、アテローム硬化性病変(血管形成術またはステントに伴って認められる)、病変切除(動脈内膜切除に伴って認められる)、外的傷害(例えば、クロスクランピングによる傷害)、または外科的吻合に対する外傷が含まれる。
II.組成物
自然免疫細胞
マクロファージ
血小板
A.LYST
1.LYST遺伝子
2.LYSTタンパク質
C.LYSTのインヒビター
1.抗体
2.機能的核酸
i.アンチセンス分子
ii.アプタマー
iii.リボザイム
iv.三重鎖形成オリゴヌクレオチド
v.外部ガイド配列
vi.RNA干渉
B.賦形剤、送達ビヒクル、およびデバイス
1.非経口投与
2.肺または粘膜への投与
3.局部投与および経皮投与
4.制御送達マトリックス
5.グラフトおよび医療デバイス
グラフト
組織工学血管グラフト
バイパスグラフト
動静脈グラフト
医療デバイス
ステント
バイオプロテーゼ
IV.使用方法
A.処置すべき障害および疾患
血管増殖性障害
血管傷害
内膜過形成
狭窄
再狭窄
アテローム性動脈硬化症
血管形成術
移植片動脈症
過剰な瘢痕化
肥厚性瘢痕化
ケロイド
癒着
他の線維増殖性疾患
肝硬変
肺線維症
他の線維症性疾患
血小板機能に関連する疾患
B.処置方法
コントロール
グラフトおよびデバイス上のコーティング
C.投薬量および有効量
D.併用療法
実施例1:ベージュ変異は組織グラフトにおける狭窄を軽減する
方法及び材料
組織工学血管グラフト(TEVG)を、ポリ乳酸とポリカプロラクトンとの50:50コポリマーでコーティングしたポリグリコール酸繊維の管から製作された生分解性管状足場上に自己骨髄由来単核球を播種することによって開発した。
結果
方法及び材料
結果
実施例3:ベージュ表現型はLYST遺伝子の変異から生じる
方法及び材料
結果
実施例4:LYST遺伝子のベージュ変異は免疫過程を変化させる
方法及び材料
結果
実施例5:LYSTタンパク質に対する抗体を使用してLYST媒介性免疫調節を行うことができる
方法及び材料
結果
実施例6:機能的Lyst遺伝子を欠くトランスジェニックマウスは、TEVGの狭窄を示さない
方法及び材料
結果
実施例7:Lystは、活性化に応答して血小板機能を調整する
方法及び材料
結果
Claims (40)
- 被験体におけるマクロファージ浸潤、瘢痕形成または狭窄を軽減もしくは防止する方法において使用するための薬学的組成物であって、該薬学的組成物が、
薬学的に許容され得るキャリア中に、該被験体において正常な創傷治癒を防止することなくマクロファージ浸潤、ナチュラルキラー細胞活性化、および/または血小板活性化を軽減もしくは防止するのに有効な量の1つまたはそれを超えるリソソーム輸送制御因子(LYST)のインヒビターであって、抗LYST抗体の結合特異性を有する抗体、抗LYST抗体の結合特異性を有する抗体フラグメント、少なくとも抗LYST抗体の抗原結合可変ドメインを含み、かつ、抗LYST抗体の結合特異性を有するタンパク質、ならびに機能的核酸であるアンチセンス分子、siRNA、miRNA、アプタマー、リボザイム、三重鎖形成分子、RNAiおよび外部ガイド配列からなる群から選択されるLYSTのインヒビター
を含み、該組成物が、瘢痕形成または狭窄の前に該被験体に投与されることを特徴とする、薬学的組成物。 - 0.1mg/kgヒト体重と1000mg/kgヒト体重との間の量の1つまたはそれを超えるLYSTインヒビターを送達する投薬製剤中の請求項1に記載の組成物。
- マクロファージ浸潤を軽減または防止するのに有効な投薬量の請求項1に記載の組成物。
- 血小板活性化を軽減または防止するのに有効な投薬量の請求項1に記載の組成物。
- 1つまたはそれを超える機能的核酸が発現ベクターから発現される、請求項1に記載の組成物。
- ナノ粒子、微粒子、ミセル、エマルジョン、合成リポタンパク質粒子、リポソーム、カーボンナノチューブ、ゲル、またはコーティングからなる群から選択される送達ビヒクルをさらに含む、請求項1に記載の組成物。
- 他の抗新生内膜剤、化学療法剤、ステロイド性および非ステロイド性の抗炎症薬、従来の免疫治療剤、免疫抑制剤、サイトカイン、ケモカイン、および成長因子からなる群から選択される1つまたはそれを超えるさらなる治療剤をさらに含む、請求項1に記載の組成物。
- a)被験体においてマクロファージ浸潤、ナチュラルキラー細胞活性化、および/または血小板活性化を軽減もしくは防止するのに有効な量の1つまたはそれを超えるリソソーム輸送制御因子(LYST)のインヒビターであって、抗LYST抗体の結合特異性を有する抗体、抗LYST抗体の結合特異性を有する抗体フラグメント、少なくとも抗LYST抗体の抗原結合可変ドメインを含み、かつ、抗LYST抗体の結合特異性を有するタンパク質、ならびに機能的核酸であるアンチセンス分子、siRNA、miRNA、アプタマー、リボザイム、三重鎖形成分子、RNAiおよび外部ガイド配列からなる群から選択されるLYSTのインヒビター;および
b)生理学的に許容され得るキャリア
を含む血管グラフトであって、該量の1つまたはそれを超えるLYSTのインヒビターが、該被験体において正常な創傷治癒を防止しない、血管グラフト。 - a)被験体においてマクロファージ浸潤、ナチュラルキラー細胞活性化、および/または血小板活性化を軽減もしくは防止するのに有効な量の1つまたはそれを超えるリソソーム輸送制御因子(LYST)のインヒビターであって、抗LYST抗体の結合特異性を有する抗体、抗LYST抗体の結合特異性を有する抗体フラグメント、少なくとも抗LYST抗体の抗原結合可変ドメインを含み、かつ、抗LYST抗体の結合特異性を有するタンパク質、ならびに機能的核酸であるアンチセンス分子、siRNA、miRNA、アプタマー、リボザイム、三重鎖形成分子、RNAiおよび外部ガイド配列からなる群から選択されるLYSTのインヒビター;および
b)生理学的に許容され得るキャリア
を含むステントであって、該量の1つまたはそれを超えるLYSTのインヒビターが、該被験体において正常な創傷治癒を防止しない、ステント。 - a)被験体においてマクロファージ浸潤、ナチュラルキラー細胞活性化、および/または血小板活性化を軽減もしくは防止するのに有効な量の1つまたはそれを超えるリソソーム輸送制御因子(LYST)のインヒビターであって、抗LYST抗体の結合特異性を有する抗体、抗LYST抗体の結合特異性を有する抗体フラグメント、少なくとも抗LYST抗体の抗原結合可変ドメインを含み、かつ、抗LYST抗体の結合特異性を有するタンパク質、ならびに機能的核酸であるアンチセンス分子、siRNA、miRNA、アプタマー、リボザイム、三重鎖形成分子、RNAiおよび外部ガイド配列からなる群から選択されるLYSTのインヒビター;および
b)生理学的に許容され得るキャリア
を含む植込物であって、該量の1つまたはそれを超えるLYSTのインヒビターが、該被験体において正常な創傷治癒を防止しない、植込物。 - 前記1つまたはそれを超えるリソソーム輸送制御因子(LYST)のインヒビターが前記グラフト上にコーティングされているか、該グラフト内に組み込まれている、請求項8に記載の血管グラフト。
- 前記1つまたはそれを超えるリソソーム輸送制御因子(LYST)のインヒビターが、植込物上にコーティングされているか、該植込物内に組み込まれている、請求項10に記載の植込物。
- 前記1つまたはそれを超えるリソソーム輸送制御因子(LYST)のインヒビターが、ステント上にコーティングされているか、該ステント内に組み込まれている、請求項9に記載のステント。
- 前記ステントが、前記1つまたはそれを超えるリソソーム輸送制御因子(LYST)のインヒビターを溶出する薬剤溶出性ステントである、請求項13に記載のステント。
- 前記グラフトが、自己グラフト、保存自己グラフト、同種異系グラフト、異種グラフト、または合成グラフトである、請求項8に記載の血管グラフト。
- 被験体においてマクロファージ浸潤、瘢痕形成または狭窄を軽減または防止するための、請求項8、11および15のいずれか1項に記載の血管グラフト、請求項9、13および14のいずれか1項に記載のステント、または請求項10もしくは12に記載の植込物。
- 他の抗新生内膜剤、化学療法剤、ステロイド性および非ステロイド性の抗炎症薬、従来の免疫治療剤、免疫抑制剤、サイトカイン、ケモカイン、および成長因子からなる群から選択される1つまたはそれを超えるさらなる治療剤をさらに含む、請求項16に記載の血管グラフト、ステントまたは植込物。
- 瘢痕形成を軽減、減少、または防止するための、請求項1〜7のいずれか1項に記載の組成物あるいは請求項16または17に記載の血管グラフト、ステントまたは植込物。
- 心筋梗塞を防止するための、請求項1〜7のいずれか1項に記載の組成物あるいは請求項16または17に記載の血管グラフト、ステントまたは植込物。
- 肝線維症を減少させるための、請求項1〜7のいずれか1項に記載の組成物あるいは請求項16または17に記載の血管グラフト、ステントまたは植込物。
- ケロイドまたは癒着を減少させるための、請求項1〜7のいずれか1項に記載の組成物あるいは請求項16または17に記載の血管グラフト、ステントまたは植込物。
- 被験体において血小板活性化および動脈血栓症または静脈血栓症を軽減または防止するための、請求項1〜7のいずれか1項に記載の組成物あるいは請求項16または17に記載の血管グラフト、ステントまたは植込物。
- 前記被験体が、再狭窄または他の血管増殖障害のリスクが有るか、再狭窄または他の血管増殖障害を有する、請求項16または17に記載の血管グラフト、ステントまたは植込物。
- 前記被験体は、血管外傷、血管形成術、血管手術、または移植動脈症を経験していたか、経験しているか、経験する、請求項16または17に記載の血管グラフト、ステントまたは植込物。
- 非処置コントロール被験体と比較して、被験体における瘢痕組織の形成の軽減または防止、治癒の促進、肥厚性瘢痕化、ケロイド、または癒着の発症の軽減または防止、肝臓の線維症、肺の線維症、心臓の線維症、または腎臓の線維症の軽減または防止、新生内膜形成、狭窄、または再狭窄の軽減または防止、血栓症の軽減または防止、またはその任意の組み合わせのために使用する、請求項18〜22のいずれか1項に記載の組成物あるいは請求項16〜22のいずれか1項に記載の血管グラフト、ステントまたは植込物。
- 瘢痕組織の形成の軽減または防止により、ペースメーカー、神経刺激器、置換心臓弁、および人工関節からなる群から選択される1つまたはそれを超えるバイオプロテーゼデバイスの組み込みを促進するが、被包を遮断する、請求項16に記載の血管グラフト、ステントまたは植込物。
- 瘢痕組織の形成の軽減または防止が、非処置コントロール被験体と比較して、被験体における血管植込物の植込の部位、血管傷害の部位、または手術の部位での新生内膜形成の処置または防止に有効である、請求項16に記載の血管グラフト、ステントまたは植込物。
- 非処置コントロール被験体と比較して、被験体における血小板由来成長因子、トランスフォーミング成長因子β、またはその任意の組み合わせの発現を軽減または防止するために使用する、請求項18〜22のいずれか1項に記載の組成物あるいは請求項16〜22のいずれか1項に記載の血管グラフト、ステントまたは植込物。
- 血管グラフトの狭窄または再狭窄を軽減する方法において使用するための組成物であって、該方法は、被験体への該グラフトの植込前に、該グラフトを該組成物でex vivoにて処置することを含み、該組成物が、
a)被験体においてマクロファージ浸潤、ナチュラルキラー細胞活性化、および/または血小板活性化を軽減もしくは防止するのに有効な量の1つまたはそれを超えるリソソーム輸送制御因子(LYST)のインヒビターであって、抗LYST抗体の結合特異性を有する抗体、抗LYST抗体の結合特異性を有する抗体フラグメント、少なくとも抗LYST抗体の抗原結合可変ドメインを含み、かつ、抗LYST抗体の結合特異性を有するタンパク質、ならびに機能的核酸であるアンチセンス分子、siRNA、miRNA、アプタマー、リボザイム、三重鎖形成分子、RNAiおよび外部ガイド配列からなる群から選択されるLYSTのインヒビター;および
b)生理学的に許容され得るキャリア
を含み、該量の1つまたはそれを超えるLYSTのインヒビターが、該被験体において正常な創傷治癒を防止しない、組成物。 - 0.1mg/kgヒト体重と1000mg/kgヒト体重との間の量の1つまたはそれを超えるLYSTインヒビターを送達する投薬製剤中の請求項29に記載の組成物。
- マクロファージ浸潤を軽減または防止するのに有効な投薬量の請求項29に記載の組成物。
- 血小板活性化を軽減または防止するのに有効な投薬量の請求項29に記載の組成物。
- 1つまたはそれを超える機能的核酸が発現ベクターから発現される、請求項29に記載の組成物。
- ナノ粒子、微粒子、ミセル、エマルジョン、合成リポタンパク質粒子、リポソーム、カーボンナノチューブ、ゲル、またはコーティングからなる群から選択される送達ビヒクルをさらに含む、請求項29〜33のいずれか1項に記載の組成物。
- 他の抗新生内膜剤、化学療法剤、ステロイド性および非ステロイド性の抗炎症薬、従来の免疫治療剤、免疫抑制剤、サイトカイン、ケモカイン、および成長因子からなる群から選択される1つまたはそれを超えるさらなる治療剤をさらに含む、請求項29〜34のいずれか1項に記載の組成物。
- 被験体におけるマクロファージ浸潤、瘢痕形成または狭窄を軽減もしくは防止するための組成物であって、該組成物が、以下:
a)被験体においてマクロファージ浸潤、ナチュラルキラー細胞活性化、および/または血小板活性化を軽減もしくは防止するのに有効な量の1つまたはそれを超えるリソソーム輸送制御因子(LYST)のインヒビターであって、抗LYST抗体の結合特異性を有する抗体、抗LYST抗体の結合特異性を有する抗体フラグメント、少なくとも抗LYST抗体の抗原結合可変ドメインを含み、かつ、抗LYST抗体の結合特異性を有するタンパク質、ならびに機能的核酸であるアンチセンス分子、siRNA、miRNA、アプタマー、リボザイム、三重鎖形成分子、RNAiおよび外部ガイド配列からなる群から選択されるLYSTのインヒビター;および
b)生理学的に許容され得るキャリア
を含み、該量の1つまたはそれを超えるLYSTのインヒビターが、該被験体における正常な創傷治癒を可能にし、
該組成物が、0.1mg/kgヒト体重と1000mg/kgヒト体重との間の量の1つまたはそれを超えるLYSTインヒビターを送達する投薬製剤中にある、組成物。 - マクロファージ浸潤を軽減または防止するのに有効な投薬量の請求項36に記載の組成物。
- 血小板活性化を軽減または防止するのに有効な投薬量の請求項37に記載の組成物。
- ナノ粒子、微粒子、ミセル、エマルジョン、合成リポタンパク質粒子、リポソーム、カーボンナノチューブ、ゲル、またはコーティングからなる群から選択される送達ビヒクルをさらに含む、請求項36〜38のいずれか1項に記載の組成物。
- 他の抗新生内膜剤、化学療法剤、ステロイド性および非ステロイド性の抗炎症薬、従来の免疫治療剤、免疫抑制剤、サイトカイン、ケモカイン、および成長因子からなる群から選択される1つまたはそれを超えるさらなる治療剤をさらに含む、請求項36〜39のいずれか1項に記載の組成物。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2019098654A JP7343305B2 (ja) | 2014-05-02 | 2019-05-27 | 抗lystによる免疫調整のための組成物及び方法 |
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201461987910P | 2014-05-02 | 2014-05-02 | |
US61/987,910 | 2014-05-02 | ||
PCT/US2015/029014 WO2015168674A1 (en) | 2014-05-02 | 2015-05-04 | Compositions and methods for anti-lyst immunomodulation |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2019098654A Division JP7343305B2 (ja) | 2014-05-02 | 2019-05-27 | 抗lystによる免疫調整のための組成物及び方法 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2017514844A JP2017514844A (ja) | 2017-06-08 |
JP6533797B2 true JP6533797B2 (ja) | 2019-06-19 |
Family
ID=53190038
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2016565483A Active JP6533797B2 (ja) | 2014-05-02 | 2015-05-04 | 抗lystによる免疫調整のための組成物及び方法 |
JP2019098654A Active JP7343305B2 (ja) | 2014-05-02 | 2019-05-27 | 抗lystによる免疫調整のための組成物及び方法 |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2019098654A Active JP7343305B2 (ja) | 2014-05-02 | 2019-05-27 | 抗lystによる免疫調整のための組成物及び方法 |
Country Status (11)
Country | Link |
---|---|
US (2) | US20170073401A1 (ja) |
EP (1) | EP3137054B1 (ja) |
JP (2) | JP6533797B2 (ja) |
KR (1) | KR102492647B1 (ja) |
CN (1) | CN106456771B9 (ja) |
AU (2) | AU2015252805B2 (ja) |
CA (1) | CA2947494C (ja) |
ES (1) | ES2883837T3 (ja) |
IL (1) | IL248513B (ja) |
RU (1) | RU2728703C2 (ja) |
WO (1) | WO2015168674A1 (ja) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP6957468B2 (ja) | 2015-12-11 | 2021-11-02 | リサーチ インスティチュート アット ネイションワイド チルドレンズ ホスピタル | 最適化された患者特異的組織操作血管移植片のためのシステムおよび方法 |
CN109112211A (zh) * | 2018-05-15 | 2019-01-01 | 广州达瑞生殖技术有限公司 | 一种人类胚胎Chediak-Higashi综合征LYST基因突变检测的引物组合及方法 |
CN112385651A (zh) * | 2020-11-30 | 2021-02-23 | 南开沧州渤海新区绿色化工研究有限公司 | 草铵膦保湿增效组合物及制备方法 |
Family Cites Families (73)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
DE3883899T3 (de) | 1987-03-18 | 1999-04-22 | Sb2, Inc., Danville, Calif. | Geänderte antikörper. |
US5133732A (en) | 1987-10-19 | 1992-07-28 | Medtronic, Inc. | Intravascular stent |
US5891108A (en) | 1994-09-12 | 1999-04-06 | Cordis Corporation | Drug delivery stent |
CA2186029C (en) | 1995-03-01 | 2003-04-08 | Brian J. Brown | Improved longitudinally flexible expandable stent |
US6821506B2 (en) | 1995-06-08 | 2004-11-23 | Barnes-Jewish Hospital | Site specific binding system, imaging compositions and methods |
US5922554A (en) * | 1995-10-30 | 1999-07-13 | The Regents Of The University Of California | Inhibition of cellular uptake of cholesterol |
WO1997028262A1 (en) * | 1996-02-01 | 1997-08-07 | University Of Florida | Lyst1 and lyst2 gene compositions and methods of use |
US6520983B1 (en) | 1998-03-31 | 2003-02-18 | Scimed Life Systems, Inc. | Stent delivery system |
US6194551B1 (en) | 1998-04-02 | 2001-02-27 | Genentech, Inc. | Polypeptide variants |
AU3214099A (en) * | 1998-04-03 | 1999-10-25 | Curagen Corporation | Lyst protein complexes and lyst interacting proteins |
GB9809951D0 (en) | 1998-05-08 | 1998-07-08 | Univ Cambridge Tech | Binding molecules |
US6261319B1 (en) | 1998-07-08 | 2001-07-17 | Scimed Life Systems, Inc. | Stent |
US6042597A (en) | 1998-10-23 | 2000-03-28 | Scimed Life Systems, Inc. | Helical stent design |
US8257425B2 (en) | 1999-01-13 | 2012-09-04 | Boston Scientific Scimed, Inc. | Stent with protruding branch portion for bifurcated vessels |
US7220401B2 (en) | 1999-09-24 | 2007-05-22 | Barnes-Jewish Hospital | Blood clot-targeted nanoparticles |
US20080247943A1 (en) | 1999-09-24 | 2008-10-09 | Gregory Lanza | Blood Clot-Targeted Nanoparticles |
EP1132060A2 (en) | 2000-03-09 | 2001-09-12 | LPL Systems Inc. | Expandable stent |
WO2001095834A1 (en) | 2000-06-13 | 2001-12-20 | Scimed Life Systems, Inc. | Disintegrating stent and method of making same |
US6676963B1 (en) | 2000-10-27 | 2004-01-13 | Barnes-Jewish Hospital | Ligand-targeted emulsions carrying bioactive agents |
WO2002044321A2 (en) | 2000-12-01 | 2002-06-06 | MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. | Rna interference mediating small rna molecules |
US7014654B2 (en) | 2001-11-30 | 2006-03-21 | Scimed Life Systems, Inc. | Stent designed for the delivery of therapeutic substance or other agents |
AU2003209392B2 (en) | 2002-01-24 | 2008-10-09 | Barnes Jewish Hospital | Integrin targeted imaging agents |
US7789903B2 (en) | 2002-04-04 | 2010-09-07 | Boston Scientific Scimed, Inc. | Stent-graft with adjustable length |
US6986785B2 (en) | 2002-05-03 | 2006-01-17 | Medtronic Vascular, Inc. | Stent balloon assembly and methods of making same |
DE10221076A1 (de) | 2002-05-11 | 2003-11-27 | Ruesch Willy Gmbh | Stent |
US20040002752A1 (en) | 2002-06-26 | 2004-01-01 | Scimed Life Systems, Inc. | Sacrificial anode stent system |
US7144419B2 (en) | 2003-01-24 | 2006-12-05 | Medtronic Vascular, Inc. | Drug-polymer coated stent with blended phenoxy and styrenic block copolymers |
US6918929B2 (en) | 2003-01-24 | 2005-07-19 | Medtronic Vascular, Inc. | Drug-polymer coated stent with pegylated styrenic block copolymers |
US7163555B2 (en) | 2003-04-08 | 2007-01-16 | Medtronic Vascular, Inc. | Drug-eluting stent for controlled drug delivery |
US6945992B2 (en) | 2003-04-22 | 2005-09-20 | Medtronic Vascular, Inc. | Single-piece crown stent |
WO2005011561A2 (en) | 2003-08-04 | 2005-02-10 | Labcoat, Ltd. | Stent coating apparatus and method |
US8298280B2 (en) | 2003-08-21 | 2012-10-30 | Boston Scientific Scimed, Inc. | Stent with protruding branch portion for bifurcated vessels |
PL1667743T3 (pl) * | 2003-09-29 | 2008-06-30 | Hemoteq Ag | Biokompatybilne, biostabilne pokrycie powierzchni medycznych |
US7744645B2 (en) | 2003-09-29 | 2010-06-29 | Medtronic Vascular, Inc. | Laminated drug-polymer coated stent with dipped and cured layers |
US7060090B2 (en) | 2003-10-15 | 2006-06-13 | Medtronic Vascular, Inc. | Stent with increased longitudinal flexibility and scaffolding |
US8157855B2 (en) | 2003-12-05 | 2012-04-17 | Boston Scientific Scimed, Inc. | Detachable segment stent |
WO2005115405A1 (en) | 2004-04-28 | 2005-12-08 | Molecules For Health, Inc. | Methods for treating or preventing restenosis and other vascular proliferative disorders |
WO2005112570A2 (en) | 2004-05-12 | 2005-12-01 | Medtronic Vascular, Inc. | Drug-polymer coated stent |
US8048149B2 (en) | 2004-05-13 | 2011-11-01 | Medtronic Vascular, Inc. | Intraluminal stent including therapeutic agent delivery pads, and method of manufacturing the same |
AU2005326322B2 (en) | 2004-07-01 | 2009-02-05 | Yale University | Targeted and high density drug loaded polymeric materials |
US7323008B2 (en) | 2004-08-09 | 2008-01-29 | Medtronic Vascular, Inc. | Flexible stent |
WO2006096499A2 (en) | 2005-03-04 | 2006-09-14 | Washington University | Mr coronary angiography with a fluorinated nanoparticle contrast agent at 1.5 t |
US7396366B2 (en) | 2005-05-11 | 2008-07-08 | Boston Scientific Scimed, Inc. | Ureteral stent with conforming retention structure |
US8231669B2 (en) | 2005-09-22 | 2012-07-31 | Boston Scientific Scimed, Inc. | Tether guided stent side branch |
CA2635604A1 (en) | 2005-12-02 | 2007-06-07 | Barnes-Jewish Hospital | Methods to ameliorate and image angioplasty-induced vascular injury |
US8298278B2 (en) | 2006-03-07 | 2012-10-30 | Boston Scientific Scimed, Inc. | Bifurcated stent with improvement securement |
US8348991B2 (en) | 2006-03-29 | 2013-01-08 | Boston Scientific Scimed, Inc. | Stent with overlap and high expansion |
US7678141B2 (en) | 2006-04-18 | 2010-03-16 | Medtronic Vascular, Inc. | Stent graft having a flexible, articulable, and axially compressible branch graft |
US8066760B2 (en) | 2006-04-18 | 2011-11-29 | Medtronic Vascular, Inc. | Stent with movable crown |
US20070258908A1 (en) | 2006-04-27 | 2007-11-08 | Lanza Gregory M | Detection and imaging of target tissue |
EP2043567B1 (en) | 2006-06-30 | 2011-07-13 | Boston Scientific Limited | Stent design with variable expansion columns along circumference |
US20110301098A1 (en) * | 2006-07-21 | 2011-12-08 | Quax Paul H A | Treatment for intimal hyperplasia and related conditions |
US8414637B2 (en) | 2006-09-08 | 2013-04-09 | Boston Scientific Scimed, Inc. | Stent |
US8257431B2 (en) | 2006-11-01 | 2012-09-04 | Boston Scientific Scimed, Inc. | Multi-furcated ePTFE grafts and stent-graft prostheses and methods of making the same |
US8398695B2 (en) | 2006-11-03 | 2013-03-19 | Boston Scientific Scimed, Inc. | Side branch stenting system using a main vessel constraining side branch access balloon and side branching stent |
US8052732B2 (en) | 2006-11-14 | 2011-11-08 | Medtronic Vascular, Inc. | Delivery system for stent-graft with anchoring pins |
US7651527B2 (en) | 2006-12-15 | 2010-01-26 | Medtronic Vascular, Inc. | Bioresorbable stent |
US20100076544A1 (en) * | 2007-01-30 | 2010-03-25 | Erika Hoffmann | Biodegradable vascular support |
US20100151436A1 (en) | 2007-03-02 | 2010-06-17 | Fong Peter M | Methods for Ex Vivo Administration of Drugs to Grafts Using Polymeric Nanoparticles |
US8187284B2 (en) | 2007-04-23 | 2012-05-29 | Boston Scientific Scimed, Inc. | Intraluminary stent relocating apparatus |
US8372138B2 (en) | 2007-06-12 | 2013-02-12 | Boston Scientific Scimed, Inc. | Shape memory polymeric stent |
US8252048B2 (en) | 2008-03-19 | 2012-08-28 | Boston Scientific Scimed, Inc. | Drug eluting stent and method of making the same |
US8100960B2 (en) | 2008-03-20 | 2012-01-24 | Medtronic Vascular, Inc. | Bloused stent-graft and fenestration method |
US8034099B2 (en) | 2008-03-27 | 2011-10-11 | Medtronic Vascular, Inc. | Stent prosthesis having select flared crowns |
US8414639B2 (en) | 2008-07-08 | 2013-04-09 | Boston Scientific Scimed, Inc. | Closed-cell flexible stent hybrid |
US8414656B2 (en) | 2008-12-05 | 2013-04-09 | Boston Scientific Scimed, Inc. | Porous ureteral stent |
US7942917B2 (en) | 2009-04-17 | 2011-05-17 | Medtronic Vascular, Inc. | Hollow helical stent system |
WO2011084700A1 (en) | 2009-12-17 | 2011-07-14 | The Washington University | Antithrombotic nanoparticle |
US8361140B2 (en) | 2009-12-29 | 2013-01-29 | Boston Scientific Scimed, Inc. | High strength low opening pressure stent design |
US8348993B2 (en) | 2010-03-29 | 2013-01-08 | Boston Scientific Scimed, Inc. | Flexible stent design |
US8353952B2 (en) | 2010-04-07 | 2013-01-15 | Medtronic Vascular, Inc. | Stent with therapeutic substance |
RU2440128C1 (ru) * | 2010-05-17 | 2012-01-20 | Государственное образовательное учреждение дополнительного профессионального образования "Санкт-Петербургская медицинская академия последипломного образования Федерального агентства по здравоохранению и социальному развитию" (ГОУ ДПО СПбМАПО Росздрава) | Способ комплексной патогенетической терапии острых форм вирусного гепатита в и микст-гепатитов (в+с, в+d, в+с+d) |
-
2015
- 2015-05-04 KR KR1020167033755A patent/KR102492647B1/ko active IP Right Grant
- 2015-05-04 JP JP2016565483A patent/JP6533797B2/ja active Active
- 2015-05-04 EP EP15723611.8A patent/EP3137054B1/en active Active
- 2015-05-04 CN CN201580029580.XA patent/CN106456771B9/zh active Active
- 2015-05-04 CA CA2947494A patent/CA2947494C/en active Active
- 2015-05-04 ES ES15723611T patent/ES2883837T3/es active Active
- 2015-05-04 US US15/308,445 patent/US20170073401A1/en not_active Abandoned
- 2015-05-04 WO PCT/US2015/029014 patent/WO2015168674A1/en active Application Filing
- 2015-05-04 RU RU2016147083A patent/RU2728703C2/ru active
- 2015-05-04 AU AU2015252805A patent/AU2015252805B2/en active Active
-
2016
- 2016-10-26 IL IL248513A patent/IL248513B/en unknown
-
2018
- 2018-07-13 AU AU2018205184A patent/AU2018205184B2/en active Active
-
2019
- 2019-05-27 JP JP2019098654A patent/JP7343305B2/ja active Active
-
2020
- 2020-11-13 US US17/098,076 patent/US20210238266A1/en active Pending
Also Published As
Publication number | Publication date |
---|---|
CN106456771B9 (zh) | 2021-07-20 |
EP3137054B1 (en) | 2021-07-07 |
EP3137054A1 (en) | 2017-03-08 |
WO2015168674A1 (en) | 2015-11-05 |
US20210238266A1 (en) | 2021-08-05 |
CN106456771A (zh) | 2017-02-22 |
JP7343305B2 (ja) | 2023-09-12 |
AU2018205184A1 (en) | 2018-08-02 |
AU2015252805A1 (en) | 2016-11-03 |
BR112016025559A2 (pt) | 2018-01-16 |
AU2015252805B2 (en) | 2018-05-10 |
RU2016147083A (ru) | 2018-06-05 |
IL248513A0 (en) | 2016-12-29 |
US20170073401A1 (en) | 2017-03-16 |
RU2016147083A3 (ja) | 2018-06-05 |
CN106456771B (zh) | 2021-06-15 |
ES2883837T3 (es) | 2021-12-09 |
RU2728703C2 (ru) | 2020-07-31 |
KR102492647B1 (ko) | 2023-01-30 |
CA2947494A1 (en) | 2015-11-05 |
JP2017514844A (ja) | 2017-06-08 |
IL248513B (en) | 2022-02-01 |
AU2018205184B2 (en) | 2020-04-30 |
JP2019135267A (ja) | 2019-08-15 |
KR20170007334A (ko) | 2017-01-18 |
CA2947494C (en) | 2020-10-20 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US20210238266A1 (en) | Compositions and methods for anti-lyst immunomodulation | |
Liu et al. | RNAi functionalized collagen-chitosan/silicone membrane bilayer dermal equivalent for full-thickness skin regeneration with inhibited scarring | |
US8507437B2 (en) | Apoptosis-modulating p53 protein therapy for vascular disorders and nanoparticles containing the same | |
EP2482828B1 (en) | Hematopoietic stem cells for use in the treatment of a kidney injury | |
US11246965B2 (en) | Compositions and methods for reducing neointima formation | |
US20220226542A1 (en) | Compositions and methods for promoting patency of vascular grafts | |
US20110091486A1 (en) | Inhibition of post-radiation tumor growth | |
BR112016025559B1 (pt) | Composição farmacêutica, enxerto vascular, stent, ou implante, composição para a redução ou prevenção da infiltração de macrófagos, da ativação de plaquetas e de estenose ou reestenose de um enxerto vascular | |
US9233137B2 (en) | Dendritic cell modulation in post-ischemic wounds | |
Mentkowski | Exploring Extracellular Vesicles as Therapeutic Vectors: From Surface Engineering for Enhanced Cardiac Retention to Immunomodulation | |
Wang et al. | Enhancing angiogenesis in Peri-Implant soft tissue with bioactive silk fibroin microgroove coatings on zirconia surfaces | |
Bashmail | The fabrication of PLGA-Fe3O4-magnetic nanoparticles for targeted delivery of γ-secretase inhibitors to vascular stents | |
Kipshidze et al. | ENDOLUMINAL TRANSPLANTATION OF ENDOTHELIAL CELLS | |
Beohar et al. | Cytokine treatment for cardioprotection and cardiac regeneration | |
CA2711818A1 (en) | Method of reducing the effects of cytostatic drugs on bone marrow derived cells, and methods of screening |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20170105 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20170510 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20180202 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20180409 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20180702 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20181114 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20190213 |
|
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: 20190426 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20190527 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6533797 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 |