JP2001523648A - ２種の活性剤を含むコンジュゲート - Google Patents
２種の活性剤を含むコンジュゲートInfo
- Publication number
- JP2001523648A JP2001523648A JP2000520816A JP2000520816A JP2001523648A JP 2001523648 A JP2001523648 A JP 2001523648A JP 2000520816 A JP2000520816 A JP 2000520816A JP 2000520816 A JP2000520816 A JP 2000520816A JP 2001523648 A JP2001523648 A JP 2001523648A
- Authority
- JP
- Japan
- Prior art keywords
- fibrinogen
- conjugate
- factor viii
- carrier
- microcapsules
- 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
- 239000012190 activator Substances 0.000 title description 5
- 229940012952 fibrinogen Drugs 0.000 claims abstract description 56
- 102000008946 Fibrinogen Human genes 0.000 claims abstract description 55
- 108010049003 Fibrinogen Proteins 0.000 claims abstract description 54
- 239000003094 microcapsule Substances 0.000 claims abstract description 40
- 108010054218 Factor VIII Proteins 0.000 claims abstract description 39
- 102000001690 Factor VIII Human genes 0.000 claims abstract description 39
- 229960000301 factor viii Drugs 0.000 claims abstract description 38
- 239000013543 active substance Substances 0.000 claims abstract description 21
- 125000000524 functional group Chemical group 0.000 claims abstract description 15
- 102000008100 Human Serum Albumin Human genes 0.000 claims description 22
- 108091006905 Human Serum Albumin Proteins 0.000 claims description 22
- 102000004169 proteins and genes Human genes 0.000 claims description 21
- 108090000623 proteins and genes Proteins 0.000 claims description 21
- 238000000034 method Methods 0.000 claims description 15
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- 238000004519 manufacturing process Methods 0.000 claims description 2
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims 1
- 102000009027 Albumins Human genes 0.000 abstract description 5
- 108010088751 Albumins Proteins 0.000 abstract description 5
- 239000000969 carrier Substances 0.000 abstract description 2
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- OAKJQQAXSVQMHS-UHFFFAOYSA-N hydrazine group Chemical group NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 4
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- 238000011068 loading method Methods 0.000 description 4
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- 206010028980 Neoplasm Diseases 0.000 description 3
- IBVAQQYNSHJXBV-UHFFFAOYSA-N adipic acid dihydrazide Chemical compound NNC(=O)CCCCC(=O)NN IBVAQQYNSHJXBV-UHFFFAOYSA-N 0.000 description 3
- 230000002776 aggregation Effects 0.000 description 3
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- 239000000126 substance Substances 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
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- IYMAXBFPHPZYIK-BQBZGAKWSA-N Arg-Gly-Asp Chemical compound NC(N)=NCCC[C@H](N)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(O)=O IYMAXBFPHPZYIK-BQBZGAKWSA-N 0.000 description 2
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
- 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 2
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- SQVRNKJHWKZAKO-UHFFFAOYSA-N beta-N-Acetyl-D-neuraminic acid Natural products CC(=O)NC1C(O)CC(O)(C(O)=O)OC1C(O)C(O)CO SQVRNKJHWKZAKO-UHFFFAOYSA-N 0.000 description 2
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- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
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- 239000000376 reactant Substances 0.000 description 2
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- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000001694 spray drying Methods 0.000 description 2
- 229960004072 thrombin Drugs 0.000 description 2
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- 238000005406 washing Methods 0.000 description 2
- LLXVXPPXELIDGQ-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 3-(2,5-dioxopyrrol-1-yl)benzoate Chemical compound C=1C=CC(N2C(C=CC2=O)=O)=CC=1C(=O)ON1C(=O)CCC1=O LLXVXPPXELIDGQ-UHFFFAOYSA-N 0.000 description 1
- GVJXGCIPWAVXJP-UHFFFAOYSA-N 2,5-dioxo-1-oxoniopyrrolidine-3-sulfonate Chemical compound ON1C(=O)CC(S(O)(=O)=O)C1=O GVJXGCIPWAVXJP-UHFFFAOYSA-N 0.000 description 1
- VYMHBQQZUYHXSS-UHFFFAOYSA-N 2-(3h-dithiol-3-yl)pyridine Chemical group C1=CSSC1C1=CC=CC=N1 VYMHBQQZUYHXSS-UHFFFAOYSA-N 0.000 description 1
- DSYBJJPCWALMGQ-UHFFFAOYSA-N 3-(iminomethylideneamino)-1-n,1-n'-dimethylpentane-1,1-diamine Chemical compound N=C=NC(CC)CC(NC)NC DSYBJJPCWALMGQ-UHFFFAOYSA-N 0.000 description 1
- XCXDQEVVSKEOIO-UHFFFAOYSA-N 3-(iminomethylideneamino)-1-n,3-n-dimethylpentane-1,3-diamine Chemical compound N=C=NC(CC)(NC)CCNC XCXDQEVVSKEOIO-UHFFFAOYSA-N 0.000 description 1
- NITXODYAMWZEJY-UHFFFAOYSA-N 3-(pyridin-2-yldisulfanyl)propanehydrazide Chemical compound NNC(=O)CCSSC1=CC=CC=N1 NITXODYAMWZEJY-UHFFFAOYSA-N 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
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- 102000008186 Collagen Human genes 0.000 description 1
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- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
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- 108010076282 Factor IX Proteins 0.000 description 1
- 102000009123 Fibrin Human genes 0.000 description 1
- 108010073385 Fibrin Proteins 0.000 description 1
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 1
- 102100024783 Fibrinogen gamma chain Human genes 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- 101000631695 Homo sapiens Succinate dehydrogenase assembly factor 3, mitochondrial Proteins 0.000 description 1
- 101000649946 Homo sapiens Vacuolar protein sorting-associated protein 29 Proteins 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
- 102100025306 Integrin alpha-IIb Human genes 0.000 description 1
- 101710149643 Integrin alpha-IIb Proteins 0.000 description 1
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 1
- MKYBYDHXWVHEJW-UHFFFAOYSA-N N-[1-oxo-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propan-2-yl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(C(C)NC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 MKYBYDHXWVHEJW-UHFFFAOYSA-N 0.000 description 1
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- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
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- CKLJMWTZIZZHCS-REOHCLBHSA-N aspartic acid group Chemical group N[C@@H](CC(=O)O)C(=O)O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
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- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
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- 238000010382 chemical cross-linking Methods 0.000 description 1
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
- 229960004316 cisplatin Drugs 0.000 description 1
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- 229960004679 doxorubicin Drugs 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 229950003499 fibrin Drugs 0.000 description 1
- 108010048325 fibrinopeptides gamma Proteins 0.000 description 1
- 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 description 1
- 238000009472 formulation Methods 0.000 description 1
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- 229930182830 galactose Natural products 0.000 description 1
- 125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 description 1
- 229940042795 hydrazides for tuberculosis treatment Drugs 0.000 description 1
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- 229960000485 methotrexate Drugs 0.000 description 1
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- 150000003141 primary amines Chemical class 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- DXGIRFAFSFKYCF-UHFFFAOYSA-N propanehydrazide Chemical compound CCC(=O)NN DXGIRFAFSFKYCF-UHFFFAOYSA-N 0.000 description 1
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- 125000005629 sialic acid group Chemical group 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
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- CNHYKKNIIGEXAY-UHFFFAOYSA-N thiolan-2-imine Chemical compound N=C1CCCS1 CNHYKKNIIGEXAY-UHFFFAOYSA-N 0.000 description 1
- 206010043554 thrombocytopenia Diseases 0.000 description 1
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- 229960005356 urokinase Drugs 0.000 description 1
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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
- A61K47/51—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
- 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)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Organic Chemistry (AREA)
- Hematology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Diabetes (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Medicinal Preparation (AREA)
- Detergent Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB9724143.4A GB9724143D0 (en) | 1997-11-14 | 1997-11-14 | Pharmaceutical conjugate |
| GB9724143.4 | 1997-11-14 | ||
| PCT/GB1998/003442 WO1999025383A1 (en) | 1997-11-14 | 1998-11-16 | Conjugates comprising two active agents |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2001523648A true JP2001523648A (ja) | 2001-11-27 |
| JP2001523648A5 JP2001523648A5 (https=) | 2006-01-05 |
Family
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| JP2000520816A Pending JP2001523648A (ja) | 1997-11-14 | 1998-11-16 | ２種の活性剤を含むコンジュゲート |
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| US (1) | US7001989B2 (https=) |
| EP (1) | EP1047452B1 (https=) |
| JP (1) | JP2001523648A (https=) |
| AT (1) | ATE293459T1 (https=) |
| AU (1) | AU1165899A (https=) |
| DE (1) | DE69829880T2 (https=) |
| ES (1) | ES2238774T3 (https=) |
| GB (1) | GB9724143D0 (https=) |
| WO (1) | WO1999025383A1 (https=) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007507480A (ja) * | 2003-10-07 | 2007-03-29 | ヘモスタティクス リミテッド | 止血を促進するためのフィブリノゲン標的微粒子 |
| 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 (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6933366B2 (en) * | 1996-12-27 | 2005-08-23 | Tripep Ab | Specificity exchangers that redirect antibodies to bacterial adhesion receptors |
| WO1999064072A1 (de) * | 1998-06-10 | 1999-12-16 | Baxter Aktiengesellschaft | Konjugat, bestehend aus einem lektin und einem blutgerinnungsfaktor |
| 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 |
| AU6389000A (en) * | 1999-07-28 | 2001-02-19 | Valentis, Inc. | Sonoporation of tumors |
| JP5230610B2 (ja) | 2006-05-05 | 2013-07-10 | ザ リージェンツ オブ ザ ユニバーシティ オブ ミシガン | 二価ｓｍａｃ模倣物およびその使用 |
| GB0623607D0 (en) * | 2006-11-27 | 2007-01-03 | Haemostatix Ltd | Tissue adhesive |
| US20090170195A1 (en) * | 2007-12-28 | 2009-07-02 | Kent State University | Curcumin-hyaluronan compounds |
| JP5770161B2 (ja) * | 2009-04-06 | 2015-08-26 | ノヴォ ノルディスク アー／エス | 血小板への第ｖｉｉｉ因子タンパク質の標的送達 |
| GB201101740D0 (en) * | 2011-02-01 | 2011-03-16 | Haemostatix Ltd | Therapeutic agents with improved fibrinogen binding |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4970300A (en) * | 1985-02-01 | 1990-11-13 | New York University | Modified factor VIII |
| IL85372A (en) * | 1987-02-12 | 1992-12-01 | Us Health | Penta to nona-peptides with laminin - like activity having an amino acid sequence and anti- metastatic compositions containing them |
| WO1996039128A1 (en) | 1995-06-06 | 1996-12-12 | Hemosphere, Inc. | Protein particles for therapeutic and diagnostic use |
| US5716614A (en) * | 1994-08-05 | 1998-02-10 | Molecular/Structural Biotechnologies, Inc. | Method for delivering active agents to mammalian brains in a complex with eicosapentaenoic acid or docosahexaenoic acid-conjugated polycationic carrier |
| PT796090E (pt) * | 1994-12-16 | 2003-07-31 | Elan Drug Delivery Ltd | Microparticulas reticuladas e sua utilizacao como veiculos terapeuticos |
| ES2232862T3 (es) * | 1996-10-21 | 2005-06-01 | Quadrant Drug Delivery Limited | Sustitutos de plaquetas y procedimientos de conjugacion apropiados para su preparacion. |
-
1997
- 1997-11-14 GB GBGB9724143.4A patent/GB9724143D0/en not_active Ceased
-
1998
- 1998-11-16 AU AU11658/99A patent/AU1165899A/en not_active Abandoned
- 1998-11-16 DE DE69829880T patent/DE69829880T2/de not_active Expired - Lifetime
- 1998-11-16 AT AT98954603T patent/ATE293459T1/de active
- 1998-11-16 WO PCT/GB1998/003442 patent/WO1999025383A1/en not_active Ceased
- 1998-11-16 ES ES98954603T patent/ES2238774T3/es not_active Expired - Lifetime
- 1998-11-16 JP JP2000520816A patent/JP2001523648A/ja active Pending
- 1998-11-16 EP EP98954603A patent/EP1047452B1/en not_active Expired - Lifetime
-
2002
- 2002-11-22 US US10/302,428 patent/US7001989B2/en not_active Expired - Fee Related
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007507480A (ja) * | 2003-10-07 | 2007-03-29 | ヘモスタティクス リミテッド | 止血を促進するためのフィブリノゲン標的微粒子 |
| 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 |
|---|---|
| AU1165899A (en) | 1999-06-07 |
| US7001989B2 (en) | 2006-02-21 |
| DE69829880T2 (de) | 2005-09-22 |
| ES2238774T3 (es) | 2005-09-01 |
| WO1999025383A1 (en) | 1999-05-27 |
| GB9724143D0 (en) | 1998-01-14 |
| EP1047452B1 (en) | 2005-04-20 |
| EP1047452A1 (en) | 2000-11-02 |
| DE69829880D1 (de) | 2005-05-25 |
| US20030087826A1 (en) | 2003-05-08 |
| ATE293459T1 (de) | 2005-05-15 |
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