JP2001504813A - 代用血小板、及びそれらの製造に適した抱合法 - Google Patents
代用血小板、及びそれらの製造に適した抱合法Info
- Publication number
- JP2001504813A JP2001504813A JP51910098A JP51910098A JP2001504813A JP 2001504813 A JP2001504813 A JP 2001504813A JP 51910098 A JP51910098 A JP 51910098A JP 51910098 A JP51910098 A JP 51910098A JP 2001504813 A JP2001504813 A JP 2001504813A
- Authority
- JP
- Japan
- Prior art keywords
- fibrinogen
- product
- albumin
- protein
- spacer
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 238000000034 method Methods 0.000 title claims abstract description 41
- 230000021615 conjugation Effects 0.000 title abstract description 5
- 238000004519 manufacturing process Methods 0.000 title description 4
- 229940012952 fibrinogen Drugs 0.000 claims abstract description 84
- 108010049003 Fibrinogen Proteins 0.000 claims abstract description 81
- 102000008946 Fibrinogen Human genes 0.000 claims abstract description 81
- 102000004169 proteins and genes Human genes 0.000 claims abstract description 36
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 36
- 125000006850 spacer group Chemical group 0.000 claims description 31
- 102000008100 Human Serum Albumin Human genes 0.000 claims description 30
- 108091006905 Human Serum Albumin Proteins 0.000 claims description 30
- 108090000765 processed proteins & peptides Chemical group 0.000 claims description 19
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 16
- 102000009027 Albumins Human genes 0.000 claims description 13
- 108010088751 Albumins Proteins 0.000 claims description 13
- 239000000126 substance Substances 0.000 claims description 10
- 239000011859 microparticle Substances 0.000 claims description 9
- 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 claims description 8
- 239000004480 active ingredient Substances 0.000 claims description 8
- 230000001588 bifunctional effect Effects 0.000 claims description 8
- IYMAXBFPHPZYIK-BQBZGAKWSA-N Arg-Gly-Asp Chemical group NC(N)=NCCC[C@H](N)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(O)=O IYMAXBFPHPZYIK-BQBZGAKWSA-N 0.000 claims description 6
- 150000001875 compounds Chemical class 0.000 claims description 6
- 229940127089 cytotoxic agent Drugs 0.000 claims description 6
- 239000002254 cytotoxic agent Substances 0.000 claims description 6
- 238000001179 sorption measurement Methods 0.000 claims description 6
- 239000003153 chemical reaction reagent Substances 0.000 claims description 5
- 231100000599 cytotoxic agent Toxicity 0.000 claims description 5
- 229960004679 doxorubicin Drugs 0.000 claims description 4
- 230000008569 process Effects 0.000 claims description 4
- 239000004094 surface-active agent Substances 0.000 claims description 4
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 3
- 239000000194 fatty acid Substances 0.000 claims description 3
- 229930195729 fatty acid Natural products 0.000 claims description 3
- 150000004665 fatty acids Chemical group 0.000 claims description 3
- JDNTWHVOXJZDSN-UHFFFAOYSA-N iodoacetic acid Chemical class OC(=O)CI JDNTWHVOXJZDSN-UHFFFAOYSA-N 0.000 claims description 3
- 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 claims description 2
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 claims description 2
- 229960004316 cisplatin Drugs 0.000 claims description 2
- ODKNJVUHOIMIIZ-RRKCRQDMSA-N floxuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(F)=C1 ODKNJVUHOIMIIZ-RRKCRQDMSA-N 0.000 claims description 2
- 229960000485 methotrexate Drugs 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 claims description 2
- NNRFRJQMBSBXGO-CIUDSAMLSA-N (3s)-3-[[2-[[(2s)-2-amino-5-(diaminomethylideneamino)pentanoyl]amino]acetyl]amino]-4-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-oxobutanoic acid Chemical group NC(N)=NCCC[C@H](N)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(O)=O NNRFRJQMBSBXGO-CIUDSAMLSA-N 0.000 claims 1
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims 1
- 239000003094 microcapsule Substances 0.000 description 53
- 235000018102 proteins Nutrition 0.000 description 29
- 239000000047 product Substances 0.000 description 27
- 239000000523 sample Substances 0.000 description 15
- 150000003573 thiols Chemical class 0.000 description 15
- 239000000203 mixture Substances 0.000 description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- 239000000872 buffer Substances 0.000 description 12
- 239000008188 pellet Substances 0.000 description 12
- 239000000243 solution Substances 0.000 description 12
- 238000002965 ELISA Methods 0.000 description 11
- 230000000694 effects Effects 0.000 description 11
- 210000004881 tumor cell Anatomy 0.000 description 11
- 238000006243 chemical reaction Methods 0.000 description 10
- 239000011541 reaction mixture Substances 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- JWICNZAGYSIBAR-LEEGLKINSA-N (4s)-4-[[2-[[(2s)-2-[[(2s)-2-[[(2s)-2-aminopropanoyl]amino]-3-carboxypropanoyl]amino]-3-hydroxypropanoyl]amino]acetyl]amino]-5-[[2-[[(2s)-3-carboxy-1-[[(2s)-1-[[1-[[(2s)-1-[[(2s)-4-carboxy-1-[[2-[[2-[[2-[[(2s)-1-[[(1s)-1-carboxy-4-(diaminomethylideneamino Chemical compound NC(N)=NCCC[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)CNC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)C(CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](C)N)CC1=CC=CC=C1 JWICNZAGYSIBAR-LEEGLKINSA-N 0.000 description 8
- 101800000974 Fibrinopeptide A Proteins 0.000 description 8
- 102400000525 Fibrinopeptide A Human genes 0.000 description 8
- 229940079593 drug Drugs 0.000 description 8
- 239000003814 drug Substances 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
- 239000012153 distilled water Substances 0.000 description 7
- 238000002474 experimental method Methods 0.000 description 7
- ZHRZLXZJVUFLNY-XAMCCFCMSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-aminopropanoyl]amino]propanoyl]amino]propanoyl]amino]propanoic acid Chemical compound C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(O)=O ZHRZLXZJVUFLNY-XAMCCFCMSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 229910021538 borax Inorganic materials 0.000 description 6
- 235000010339 sodium tetraborate Nutrition 0.000 description 6
- BSVBQGMMJUBVOD-UHFFFAOYSA-N trisodium borate Chemical compound [Na+].[Na+].[Na+].[O-]B([O-])[O-] BSVBQGMMJUBVOD-UHFFFAOYSA-N 0.000 description 6
- 230000002776 aggregation Effects 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- 238000004132 cross linking Methods 0.000 description 5
- 239000003431 cross linking reagent Substances 0.000 description 5
- 102000004196 processed proteins & peptides Human genes 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- -1 sulfosuccinimidyl Chemical group 0.000 description 5
- 206010028980 Neoplasm Diseases 0.000 description 4
- 108090000190 Thrombin Proteins 0.000 description 4
- 235000001014 amino acid Nutrition 0.000 description 4
- 150000001413 amino acids Chemical class 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
- 238000011049 filling Methods 0.000 description 4
- 238000011068 loading method Methods 0.000 description 4
- 239000008363 phosphate buffer Substances 0.000 description 4
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 4
- 229920000053 polysorbate 80 Polymers 0.000 description 4
- 108020003175 receptors Proteins 0.000 description 4
- 102000005962 receptors Human genes 0.000 description 4
- 239000006228 supernatant Substances 0.000 description 4
- 229960004072 thrombin Drugs 0.000 description 4
- 238000012546 transfer Methods 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- KIUMMUBSPKGMOY-UHFFFAOYSA-N 3,3'-Dithiobis(6-nitrobenzoic acid) Chemical compound C1=C([N+]([O-])=O)C(C(=O)O)=CC(SSC=2C=C(C(=CC=2)[N+]([O-])=O)C(O)=O)=C1 KIUMMUBSPKGMOY-UHFFFAOYSA-N 0.000 description 3
- 102000008186 Collagen Human genes 0.000 description 3
- 108010035532 Collagen Proteins 0.000 description 3
- 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 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 3
- WGCNASOHLSPBMP-UHFFFAOYSA-N Glycolaldehyde Chemical compound OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 3
- 239000007987 MES buffer Substances 0.000 description 3
- 229930195725 Mannitol Natural products 0.000 description 3
- 208000007536 Thrombosis Diseases 0.000 description 3
- 206010052428 Wound Diseases 0.000 description 3
- 208000027418 Wounds and injury Diseases 0.000 description 3
- 238000004220 aggregation Methods 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 239000007853 buffer solution Substances 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 229920001436 collagen Polymers 0.000 description 3
- 229940088598 enzyme Drugs 0.000 description 3
- 210000003743 erythrocyte Anatomy 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 239000012634 fragment Substances 0.000 description 3
- 125000000524 functional group Chemical group 0.000 description 3
- 230000036541 health Effects 0.000 description 3
- 230000023597 hemostasis Effects 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000000594 mannitol Substances 0.000 description 3
- 235000010355 mannitol Nutrition 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- 239000001488 sodium phosphate Substances 0.000 description 3
- 229910000162 sodium phosphate Inorganic materials 0.000 description 3
- 238000001694 spray drying Methods 0.000 description 3
- 230000008685 targeting Effects 0.000 description 3
- CNHYKKNIIGEXAY-UHFFFAOYSA-N thiolan-2-imine Chemical compound N=C1CCCS1 CNHYKKNIIGEXAY-UHFFFAOYSA-N 0.000 description 3
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 108010054218 Factor VIII Proteins 0.000 description 2
- 102000001690 Factor VIII Human genes 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 2
- TVUWMSBGMVAHSJ-KBPBESRZSA-N Gly-Leu-Phe Chemical compound NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 TVUWMSBGMVAHSJ-KBPBESRZSA-N 0.000 description 2
- 108090000288 Glycoproteins Proteins 0.000 description 2
- 102000003886 Glycoproteins Human genes 0.000 description 2
- 208000032843 Hemorrhage Diseases 0.000 description 2
- 102100025306 Integrin alpha-IIb Human genes 0.000 description 2
- 101710149643 Integrin alpha-IIb Proteins 0.000 description 2
- 239000004472 Lysine Substances 0.000 description 2
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
- 229920001744 Polyaldehyde Polymers 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 238000005054 agglomeration Methods 0.000 description 2
- 230000004931 aggregating effect Effects 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 108010072041 arginyl-glycyl-aspartic acid Proteins 0.000 description 2
- 230000000740 bleeding effect Effects 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 150000001718 carbodiimides Chemical class 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000010382 chemical cross-linking Methods 0.000 description 2
- 238000000151 deposition Methods 0.000 description 2
- 229960000301 factor viii Drugs 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 108010066198 glycyl-leucyl-phenylalanine Proteins 0.000 description 2
- 229940106780 human fibrinogen Drugs 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 102000013415 peroxidase activity proteins Human genes 0.000 description 2
- 108040007629 peroxidase activity proteins Proteins 0.000 description 2
- 238000005375 photometry Methods 0.000 description 2
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 206010043554 thrombocytopenia Diseases 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- VRDGQQTWSGDXCU-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 2-iodoacetate Chemical compound ICC(=O)ON1C(=O)CCC1=O VRDGQQTWSGDXCU-UHFFFAOYSA-N 0.000 description 1
- NRBDPSFGHNZPRE-UHFFFAOYSA-N 1-hydroxypyrrolidine-2,5-dione;2-iodoacetic acid Chemical compound OC(=O)CI.ON1C(=O)CCC1=O NRBDPSFGHNZPRE-UHFFFAOYSA-N 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- 102100028169 BET1-like protein Human genes 0.000 description 1
- 101710138653 BET1-like protein Proteins 0.000 description 1
- 102000015081 Blood Coagulation Factors Human genes 0.000 description 1
- 108010039209 Blood Coagulation Factors Proteins 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 102100022641 Coagulation factor IX Human genes 0.000 description 1
- 206010014009 Ear haemorrhage Diseases 0.000 description 1
- 108010076282 Factor IX Proteins 0.000 description 1
- 108010073385 Fibrin Proteins 0.000 description 1
- 102000009123 Fibrin Human genes 0.000 description 1
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 1
- 102000016359 Fibronectins Human genes 0.000 description 1
- 108010067306 Fibronectins Proteins 0.000 description 1
- 108010024636 Glutathione Proteins 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 208000031220 Hemophilia Diseases 0.000 description 1
- 208000009292 Hemophilia A Diseases 0.000 description 1
- 235000003332 Ilex aquifolium Nutrition 0.000 description 1
- 241000209027 Ilex aquifolium Species 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 108010042918 Integrin alpha5beta1 Proteins 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
- UEZVMMHDMIWARA-UHFFFAOYSA-N Metaphosphoric acid Chemical compound OP(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-N 0.000 description 1
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 1
- 229920002274 Nalgene Polymers 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 241000277331 Salmonidae Species 0.000 description 1
- 102000003990 Urokinase-type plasminogen activator Human genes 0.000 description 1
- 108090000435 Urokinase-type plasminogen activator Proteins 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000004523 agglutinating effect Effects 0.000 description 1
- 230000004520 agglutination Effects 0.000 description 1
- 102000015395 alpha 1-Antitrypsin Human genes 0.000 description 1
- 108010050122 alpha 1-Antitrypsin Proteins 0.000 description 1
- 229940024142 alpha 1-antitrypsin Drugs 0.000 description 1
- 238000007112 amidation reaction Methods 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 229940064734 aminobenzoate Drugs 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000008033 biological extinction Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 229960000182 blood factors Drugs 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 230000005859 cell recognition Effects 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 239000013065 commercial product Substances 0.000 description 1
- 239000013068 control sample Substances 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 238000004807 desolvation Methods 0.000 description 1
- 150000004985 diamines Chemical class 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 229960004222 factor ix Drugs 0.000 description 1
- 229950003499 fibrin Drugs 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 239000010419 fine particle Substances 0.000 description 1
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 1
- 230000002439 hemostatic effect Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 108010044426 integrins Proteins 0.000 description 1
- 102000006495 integrins Human genes 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical group II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 238000012803 optimization experiment Methods 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000004952 protein activity Effects 0.000 description 1
- 238000011555 rabbit model Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 229960000103 thrombolytic agent Drugs 0.000 description 1
- 230000002537 thrombolytic effect Effects 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- 229960005356 urokinase Drugs 0.000 description 1
- 108010047303 von Willebrand Factor Proteins 0.000 description 1
- 102100036537 von Willebrand factor Human genes 0.000 description 1
- 229960001134 von willebrand factor Drugs 0.000 description 1
- 238000003260 vortexing Methods 0.000 description 1
- 210000004885 white matter Anatomy 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/69—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
- A61K47/6921—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere
- A61K47/6927—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere the form being a solid microparticle having no hollow or gas-filled cores
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
- A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
- A61K47/643—Albumins, e.g. HSA, BSA, ovalbumin or a Keyhole Limpet Hemocyanin [KHL]
-
- 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
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Diabetes (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Hematology (AREA)
- Molecular Biology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicinal Preparation (AREA)
- Steroid Compounds (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB9621886.2 | 1996-10-21 | ||
| GBGB9621886.2A GB9621886D0 (en) | 1996-10-21 | 1996-10-21 | Microparticles and their therapeutic use |
| GB9702652.0 | 1997-02-10 | ||
| GBGB9702652.0A GB9702652D0 (en) | 1997-02-10 | 1997-02-10 | Conjugates and their preparation |
| PCT/GB1997/002877 WO1998017319A2 (en) | 1996-10-21 | 1997-10-17 | Platelet substitutes and conjugation methods suitable for their preparation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2001504813A true JP2001504813A (ja) | 2001-04-10 |
| JP2001504813A5 JP2001504813A5 (enExample) | 2005-06-16 |
Family
ID=26310263
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP51910098A Pending JP2001504813A (ja) | 1996-10-21 | 1997-10-17 | 代用血小板、及びそれらの製造に適した抱合法 |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US5977313A (enExample) |
| EP (1) | EP1028752B1 (enExample) |
| JP (1) | JP2001504813A (enExample) |
| AR (1) | AR008680A1 (enExample) |
| AT (1) | ATE284714T1 (enExample) |
| AU (1) | AU718956B2 (enExample) |
| CA (1) | CA2269335C (enExample) |
| DE (1) | DE69731985T2 (enExample) |
| ES (1) | ES2232862T3 (enExample) |
| WO (1) | WO1998017319A2 (enExample) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2005504745A (ja) * | 2001-07-20 | 2005-02-17 | シエーリング アクチエンゲゼルシヤフト | 大環状金属錯体及び生体分子との結合体の製造のためのその使用 |
| JP2011520913A (ja) * | 2008-05-16 | 2011-07-21 | バイエル・ヘルスケア・エルエルシー | 標的化凝固因子およびそれを使用する方法 |
Families Citing this family (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6391343B1 (en) | 1991-01-15 | 2002-05-21 | Hemosphere, Inc. | Fibrinogen-coated particles for therapeutic use |
| CA2294494A1 (en) | 1997-06-05 | 1998-12-10 | Richard C. K. Yen | Fibrinogen-coated microspheres |
| GB9724143D0 (en) * | 1997-11-14 | 1998-01-14 | Andaris Ltd | Pharmaceutical conjugate |
| JP2003524437A (ja) * | 1998-02-20 | 2003-08-19 | エラン・ドラッグ・デリバリー・リミテッド | 治療に用いるためのフィブリノーゲンを含んでなる生成物 |
| GB9825105D0 (en) * | 1998-11-16 | 1999-01-13 | Andaris Ltd | Pharamaceutical conjugates |
| GB9827813D0 (en) * | 1998-12-17 | 1999-02-10 | Andaris Ltd | Pharmaceutical conjugates |
| DE19926475A1 (de) * | 1999-06-10 | 2000-12-14 | Ktb Tumorforschungs Gmbh | Träger-Pharmaka-Konjugate |
| US20040126900A1 (en) * | 2001-04-13 | 2004-07-01 | Barry Stephen E | High affinity peptide- containing nanoparticles |
| US7906102B2 (en) | 2001-10-03 | 2011-03-15 | Vanderbilt University | Ligands to radiation-induced molecules |
| US7306925B2 (en) * | 2001-11-09 | 2007-12-11 | Vanderbilt University | Phage antibodies to radiation-inducible neoantigens |
| WO2003028640A2 (en) * | 2001-10-03 | 2003-04-10 | Vanderbilt University | In vivo panning for ligands to radiation-induced molecules |
| GB0323378D0 (en) * | 2003-10-07 | 2003-11-05 | Univ Leicester | Therapeutic agent |
| GB0516091D0 (en) * | 2005-08-04 | 2005-09-14 | Haemostatix Ltd | Therapeutic agent |
| US20080015145A1 (en) * | 2006-07-11 | 2008-01-17 | Maria Gyongyossy-Issa | Mimotope receptors and inhibitors for platelet-platelet and platelet-endothelium interactions |
| GB0623607D0 (en) | 2006-11-27 | 2007-01-03 | Haemostatix Ltd | Tissue adhesive |
| CA2761903C (en) | 2009-05-28 | 2018-04-10 | Profibrix B.V. | Dry powder fibrin sealant |
| GB201101740D0 (en) | 2011-02-01 | 2011-03-16 | Haemostatix Ltd | Therapeutic agents with improved fibrinogen binding |
| WO2013019730A1 (en) | 2011-07-29 | 2013-02-07 | The Washington University | Antibodies to tip-1 and grp78 |
| GB201201751D0 (en) | 2012-02-01 | 2012-03-14 | Haemostatix Ltd | Haemostatic wound dressing |
| US20130202656A1 (en) | 2012-02-03 | 2013-08-08 | Dynasil Biomedical Corporation | Systems and kits for the fabrication of tissue patches |
| GB201204868D0 (en) | 2012-03-20 | 2012-05-02 | San Raffaele Centro Fond | Peptides |
| EP3172222A4 (en) | 2014-07-24 | 2018-03-21 | Washington University | Compositions targeting radiation-induced molecules and methods of use thereof |
| US9540548B1 (en) | 2015-08-07 | 2017-01-10 | Xcede Technologies, Inc. | Adhesive compositions and related methods |
| US9833538B2 (en) | 2015-08-07 | 2017-12-05 | Xcede Technologies, Inc. | Adhesive compositions and related methods |
| CA2994959A1 (en) | 2015-08-07 | 2017-02-16 | Xcede Technologies, Inc. | Adhesive compositions and related methods |
| CN107686507B (zh) * | 2016-08-05 | 2021-02-12 | 首都医科大学 | Rgds-阿霉素,其合成,活性和应用 |
| CN107686508B (zh) * | 2016-08-05 | 2021-02-12 | 首都医科大学 | 阿霉素-rgds,其合成,活性和应用 |
| US11352436B2 (en) | 2017-02-10 | 2022-06-07 | Washington University | Antibodies to TIP1 and methods of use thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1996039128A1 (en) * | 1995-06-06 | 1996-12-12 | Hemosphere, Inc. | Protein particles for therapeutic and diagnostic use |
Family Cites Families (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8334499D0 (en) * | 1983-12-24 | 1984-02-01 | Beecham Group Plc | Derivatives |
| GB8400653D0 (en) * | 1984-01-11 | 1984-02-15 | Beecham Group Plc | Conjugates |
| US4666884A (en) * | 1984-04-10 | 1987-05-19 | New England Deaconess Hospital | Method of inhibiting binding of von Willebrand factor to human platelets and inducing interaction of platelets with vessel walls |
| US4661471A (en) * | 1984-04-10 | 1987-04-28 | New England Deaconess Hospital | Method of inhibiting and inducing human platelet aggregation |
| US5069936A (en) * | 1987-06-25 | 1991-12-03 | Yen Richard C K | Manufacturing protein microspheres |
| AU3149289A (en) * | 1988-03-18 | 1989-09-21 | Rockefeller University, The | Method and agent for inhibiting the binding of human polymorphonuclear leukocytes to endothelium and compositions therefor |
| WO1990003401A1 (en) * | 1988-09-30 | 1990-04-05 | Neorx Corporation | Targeting substance-diagnostic/therapeutic agent conjugates having schiff base linkages |
| DK0494417T3 (da) * | 1991-01-10 | 1996-05-13 | Basf Corp | Fremgangsmåde til tværbinding af gelatine og til inkorporering af et materiale deri |
| US5725804A (en) * | 1991-01-15 | 1998-03-10 | Hemosphere, Inc. | Non-crosslinked protein particles for therapeutic and diagnostic use |
| US5616311A (en) * | 1991-01-15 | 1997-04-01 | Hemosphere, Inc. | Non-crosslinked protein particles for therapeutic and diagnostic use |
| ATE147976T1 (de) * | 1991-01-15 | 1997-02-15 | Hemosphere Inc | Protein nanomatrizen und verfahren zur herstellung |
| WO1992013547A1 (en) * | 1991-02-07 | 1992-08-20 | Alexander Mellon Eaton | Drug delivery composition and method of using the same |
| AU1461592A (en) * | 1991-02-07 | 1992-09-07 | Fibratek, Inc. | Fibrinogen based adhesive |
| GB9107628D0 (en) * | 1991-04-10 | 1991-05-29 | Moonbrook Limited | Preparation of diagnostic agents |
| EP0673384A4 (en) * | 1992-12-10 | 1996-10-09 | Univ Minnesota | POLYPEPTIDES USEFUL IN TREATING INFLAMMABLE DISEASES. |
| GB9423419D0 (en) * | 1994-11-19 | 1995-01-11 | Andaris Ltd | Preparation of hollow microcapsules |
| JP4350165B2 (ja) * | 1994-12-16 | 2009-10-21 | クアドラント、 ドラッグ、 デリバリー、 リミテッド | 架橋した微細粒子、及びそれら粒子の治療薬用ビヒクルとしての使用 |
| EP0727225A3 (en) * | 1995-02-14 | 1997-01-15 | Sonus Pharma Inc | Compositions and methods for directed ultrasonic imaging |
-
1997
- 1997-10-17 JP JP51910098A patent/JP2001504813A/ja active Pending
- 1997-10-17 CA CA2269335A patent/CA2269335C/en not_active Expired - Fee Related
- 1997-10-17 DE DE69731985T patent/DE69731985T2/de not_active Expired - Lifetime
- 1997-10-17 ES ES97909451T patent/ES2232862T3/es not_active Expired - Lifetime
- 1997-10-17 AT AT97909451T patent/ATE284714T1/de active
- 1997-10-17 AU AU47135/97A patent/AU718956B2/en not_active Ceased
- 1997-10-17 EP EP97909451A patent/EP1028752B1/en not_active Expired - Lifetime
- 1997-10-17 US US08/953,514 patent/US5977313A/en not_active Expired - Lifetime
- 1997-10-17 WO PCT/GB1997/002877 patent/WO1998017319A2/en not_active Ceased
- 1997-10-20 AR ARP970104847A patent/AR008680A1/es unknown
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1996039128A1 (en) * | 1995-06-06 | 1996-12-12 | Hemosphere, Inc. | Protein particles for therapeutic and diagnostic use |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2005504745A (ja) * | 2001-07-20 | 2005-02-17 | シエーリング アクチエンゲゼルシヤフト | 大環状金属錯体及び生体分子との結合体の製造のためのその使用 |
| JP2011520913A (ja) * | 2008-05-16 | 2011-07-21 | バイエル・ヘルスケア・エルエルシー | 標的化凝固因子およびそれを使用する方法 |
| US9422362B2 (en) | 2008-05-16 | 2016-08-23 | Bayer Healthcare Llc | Targeted coagulation factors and method of using the same |
| JP2017025065A (ja) * | 2008-05-16 | 2017-02-02 | バイエル・ヘルスケア・エルエルシーBayer HealthCare LLC | 標的化凝固因子およびそれを使用する方法 |
| US10035840B2 (en) | 2008-05-16 | 2018-07-31 | Bayer Healthcare Llc | Targeted coagulation factors and method of using the same |
Also Published As
| Publication number | Publication date |
|---|---|
| WO1998017319A3 (en) | 1998-06-11 |
| EP1028752A2 (en) | 2000-08-23 |
| ES2232862T3 (es) | 2005-06-01 |
| WO1998017319A2 (en) | 1998-04-30 |
| DE69731985T2 (de) | 2005-12-29 |
| CA2269335C (en) | 2010-05-25 |
| CA2269335A1 (en) | 1998-04-30 |
| AR008680A1 (es) | 2000-02-09 |
| US5977313A (en) | 1999-11-02 |
| AU718956B2 (en) | 2000-05-04 |
| ATE284714T1 (de) | 2005-01-15 |
| DE69731985D1 (de) | 2005-01-20 |
| AU4713597A (en) | 1998-05-15 |
| EP1028752B1 (en) | 2004-12-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2001504813A (ja) | 代用血小板、及びそれらの製造に適した抱合法 | |
| JP4350165B2 (ja) | 架橋した微細粒子、及びそれら粒子の治療薬用ビヒクルとしての使用 | |
| US5955108A (en) | Cross-linked microparticles and their use as therapeutic vehicles | |
| FI117124B (fi) | Biohajoavista kopolymeereistä koostuvia mikrohiukkasvalmisteita | |
| JPH07508004A (ja) | プロテイノイド担体並びにその製造方法および使用方法 | |
| RU2503464C2 (ru) | Биогель | |
| JP2000511169A (ja) | 微粒子および創傷治療におけるその用途 | |
| JP2939341B2 (ja) | 赤血球代用剤 | |
| JPH04504404A (ja) | 治療薬および診断薬の内皮および上皮取り込み、および障害部位への局在化のための生物付着薬物担体 | |
| EP1919508B1 (en) | Artificial platelets | |
| JP2001523648A (ja) | 2種の活性剤を含むコンジュゲート | |
| JPH09504790A (ja) | 化学的触媒作用および細胞受容体活性化のための生化学的活性物質 | |
| CN112274654B (zh) | 靶向载药纳米胶束、其制备方法和应用 | |
| CN104758945B (zh) | 一种pH响应的溶栓药物靶向纳米凝胶及其合成方法和用途 | |
| MXPA99003677A (en) | Platelet substitutes and conjugation methods suitable for their preparation | |
| CN100360554C (zh) | 肽缀合物 | |
| CN1240364A (zh) | 血小板替代物和适于其制备的缀合方法 | |
| Magee et al. | Effect of process variables on the in vitro degradation of protein microspheres | |
| WO2000035487A1 (en) | Pharmaceutical conjugates comprising two active agents | |
| US20040235719A1 (en) | Soluble protein-polymer systems for drug delivery | |
| MXPA97004503A (en) | Steril powder of interlocked materials and its | |
| WO2000029028A1 (en) | Pharmaceutical conjugates of glycoproteins and insoluble carriers |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20041014 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20041014 |
|
| A72 | Notification of change in name of applicant |
Free format text: JAPANESE INTERMEDIATE CODE: A721 Effective date: 20061129 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20080527 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20080827 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20081006 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20080922 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20081031 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20081127 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20090609 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20091009 |
|
| A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20091210 |
|
| A912 | Re-examination (zenchi) completed and case transferred to appeal board |
Free format text: JAPANESE INTERMEDIATE CODE: A912 Effective date: 20100527 |
|
| RD04 | Notification of resignation of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7424 Effective date: 20130321 |