WO1992005749A1 - Conjugues solubles d'un inhibiteur de la thrombogenese - Google Patents
Conjugues solubles d'un inhibiteur de la thrombogenese Download PDFInfo
- Publication number
- WO1992005749A1 WO1992005749A1 PCT/US1991/005353 US9105353W WO9205749A1 WO 1992005749 A1 WO1992005749 A1 WO 1992005749A1 US 9105353 W US9105353 W US 9105353W WO 9205749 A1 WO9205749 A1 WO 9205749A1
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- Prior art keywords
- inhibitor
- carrier
- thrombogenesis
- reagent
- agent
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Classifications
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- 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
- 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
- A61K47/6425—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 the peptide or protein in the drug conjugate being a receptor, e.g. CD4, a cell surface antigen, i.e. not a peptide ligand targeting the antigen, or a cell surface determinant, i.e. a part of the surface of a cell
Definitions
- Materials having varying degrees of thromboresistance have been utilized in vascular prostheses with limited success. These materials include corroding (self-cleaning) metals, synthetic polymers such as polydimethyl siloxane. Teflon, acrylates and methacrylates such as polyethylene terphthalate, electrets, anionic copolymers, and hydrogels (for a review see Salzman et al. (1987) in Hemostasis and Thrombosis, Basic Principles and Clinical Practice (Colman et al., eds.) J. B. Lippincott Co., Phila. PA, pp. 1335-1347).
- the synthetic material may be contacted with a solution which removes impurities therein and/or thereon prior to the activation step described above.
- FIGURE 6 is a graphic representation of the activities of grafts including immobilized thrombomodulin or BSA;
- Thrombogenesis inhibitors useful for these purposes include molecules which interfere with, or inhibit thrombogenesis. These include, but are not limited to, ATPase, ADPase, 5'-nucleotidase, streptokinase, urokinase, tissue plasminogen activator, thrombomodulin, anticoagulants, and platelet inhibit ' (e.g., prostacycline and aspirin) Active fragments of these thrombogenesis inhibitors may be provided by enzymatic digestion using any number of know proteolytic enzymes (e.g. trypsin, chymotrypsin) whose exact locus of cleavage along an amino acid sequence is well known in the art.
- proteolytic enzymes e.g. trypsin, chymotrypsin
- SPDP derivatization linkage of certain groups on the thrombogenesis inhibitor to SPDP may destroy some inhibitor activity because at least some of these groups may be required for such activity.
- SPDP becomes somewhat selective for epsilon amino groups. The result of these conditions favor a 1:1 (mole:mole) conjugation ratio of inhibitor to SPDP covalently bound without destroying biological activity.
- the activated material is placed into 100.0 ml of 10 mM water-soluble carbodiimide (EDC) in deionized water, pH 4.6-5.0, for 1 hour at RT with constant stirring.
- EDC water-soluble carbodiimide
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Abstract
On décrit un agent pharmacologique biocompatible soluble servant à inhiber la génération de la thrombine et la formation d'un thrombus, ainsi que des méthodes servant à produire ledit agent. L'agent ou le conjugué pharmaceutique comprend un véhicule biocompatible soluble et un inhibiteur de thrombogenèse immobilisé sur ledit véhicule par un constituant du véhicule qui lie l'inhibiteur. L'inhibiteur de thrombogenèse est un inhibiteur autre que l'hirudine, ou un analogue actif ou un fragment actif de cet inhibiteur. L'inhibiteur peut être lié au constituant du véhicule au moyen d'un réactif de liaison transversale bifonctionnel.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US59258090A | 1990-10-04 | 1990-10-04 | |
US592,580 | 1990-10-04 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1992005749A1 true WO1992005749A1 (fr) | 1992-04-16 |
Family
ID=24371262
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US1991/005353 WO1992005749A1 (fr) | 1990-10-04 | 1991-07-29 | Conjugues solubles d'un inhibiteur de la thrombogenese |
Country Status (2)
Country | Link |
---|---|
AU (1) | AU8492991A (fr) |
WO (1) | WO1992005749A1 (fr) |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0538459A1 (fr) * | 1991-05-09 | 1993-04-28 | The Board Of Regents Of The University Of Washington | Agents thrombolytiques cibles sur des phospholipides |
WO1997010509A1 (fr) * | 1995-09-13 | 1997-03-20 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V., Berlin | Inhibiteurs d'enzymes metaboliques activables lies a des complexes, utilises comme marqueurs moleculaires pour le diagnostic et le controle therapeutique |
US5632986A (en) * | 1991-05-09 | 1997-05-27 | The University Of Washington | Phospholipid-targeted thrombolytic agents |
EP1136082A1 (fr) * | 2000-03-24 | 2001-09-26 | Nederlandse Organisatie Voor Toegepast-Natuurwetenschappelijk Onderzoek Tno | Administration locale de médicaments |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1979000638A1 (fr) * | 1978-02-17 | 1979-09-06 | Thin Conductive Coating Oester | Methode de production de surfaces permettant d'eviter la formation de thrombus |
US4273873A (en) * | 1977-10-25 | 1981-06-16 | Unitika Ltd. | Preparation of antithrombogenic polymeric materials |
US5002582A (en) * | 1982-09-29 | 1991-03-26 | Bio-Metric Systems, Inc. | Preparation of polymeric surfaces via covalently attaching polymers |
-
1991
- 1991-07-29 WO PCT/US1991/005353 patent/WO1992005749A1/fr unknown
- 1991-07-29 AU AU84929/91A patent/AU8492991A/en not_active Abandoned
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4273873A (en) * | 1977-10-25 | 1981-06-16 | Unitika Ltd. | Preparation of antithrombogenic polymeric materials |
WO1979000638A1 (fr) * | 1978-02-17 | 1979-09-06 | Thin Conductive Coating Oester | Methode de production de surfaces permettant d'eviter la formation de thrombus |
US5002582A (en) * | 1982-09-29 | 1991-03-26 | Bio-Metric Systems, Inc. | Preparation of polymeric surfaces via covalently attaching polymers |
Non-Patent Citations (1)
Title |
---|
J. LAB. CLIN. MED., Volume 91, January 1978 (LINDON), "Interaction of human platelets with heparinized agarose gel", pages 47-59. * |
Cited By (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0538459A1 (fr) * | 1991-05-09 | 1993-04-28 | The Board Of Regents Of The University Of Washington | Agents thrombolytiques cibles sur des phospholipides |
EP0538459A4 (en) * | 1991-05-09 | 1993-06-16 | The Board Of Regents Of The University Of Washington | Phospholipid-targeted thrombolytic agents |
US5632986A (en) * | 1991-05-09 | 1997-05-27 | The University Of Washington | Phospholipid-targeted thrombolytic agents |
WO1997010509A1 (fr) * | 1995-09-13 | 1997-03-20 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V., Berlin | Inhibiteurs d'enzymes metaboliques activables lies a des complexes, utilises comme marqueurs moleculaires pour le diagnostic et le controle therapeutique |
US6051390A (en) * | 1995-09-13 | 2000-04-18 | Max-Planck-Gesellschaft zur Forderung der Wissenschaften E.V., Berlin | Complex-bound inhibitors of metabolic enzymes capable of being activated, useful as molecular markers for diagnostic and therapy monitoring purposes |
EP1136082A1 (fr) * | 2000-03-24 | 2001-09-26 | Nederlandse Organisatie Voor Toegepast-Natuurwetenschappelijk Onderzoek Tno | Administration locale de médicaments |
WO2001070274A2 (fr) * | 2000-03-24 | 2001-09-27 | Nederlandse Organisatie Voor Toegepast-Natuurwetenschappelijk Onderzoek Tno | Administration locale de medicaments |
WO2001070274A3 (fr) * | 2000-03-24 | 2002-03-07 | Tno | Administration locale de medicaments |
Also Published As
Publication number | Publication date |
---|---|
AU8492991A (en) | 1992-04-28 |
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