Immobilised biological entities
There is described inter alia a device having a surface comprising a layered coating wherein the outer coating layer comprises a plurality of cationic hyperbranched polymer molecules characterized by having (i) a core moiety of molecular weight 14-1,000 Da (ii) a total molecular weight of 1,500 to 1,000,000 Da (iii) a ratio of total molecular weight to core moiety molecular weight of at least 80:1 and (iv) functional end groups, whereby one or more of said functional end groups have an anti-coagulant entity covalently attached thereto.
1. A process for the manufacture of a device having a surface comprising a layered coating wherein the outer coating layer comprises a plurality of cationic hyperbranched polymer molecules characterized by having (i) a core moiety of molecular weight 14-1,000 Da (ii) a total molecular weight of 10,000 to 300,000 Da (iii) a ratio of total molecular weight to core moiety molecular weight of at least 80:1 and (iv) functional end groups, whereby one or more of said functional end groups have an anti-coagulant entity covalently attached thereto and (v) wherein the hyperbranched polymer is not a dendrimer, the process comprising, in any order:
i. reacting a plurality of functional end groups of the hyperbranched polymer molecules with anti-coagulant entities such that each hyperbranched polymer molecule is covalently linked to a plurality of anti-coagulant entities; and
ii. attaching the hyperbranched polymer molecules to the surface of a device.
2. A process according to claim 1 , further comprising the step of modifying the hyperbranched polymer molecules and/or the anti-coagulant entity before step (i) in order to introduce suitable functional groups for forming a covalent linkage between the hyperbranched polymer molecules and the anti-coagulant entity.
3. A process according to claim 1 wherein the first step of the process is step (i) and is carried out in solution.
4. A process according to claim 1 wherein the first step of the process is step (ii) and further comprises bringing the outer coating layer of the device into contact with a solution of the anti-coagulant entity.
5. A process according to claim 1 , wherein hyperbranched polymer molecules of the outer coating layer are cross-linked to other hyperbranched polymer molecules of the outer coating layer.
6. A process according to claim 1 , wherein hyperbranched polymer molecules of the outer coating layer are cross-linked to molecules (e.g. hyperbranched polymer molecules) of an underlayer.
7. A process according to claim 1 wherein the anti-coagulant entities are heparin moieties.
8. A process according to claim 1 wherein the heparin moieties are single point attached to the hyperbranched polymer molecules.
9. A process according to claim 1 , wherein the heparin moieties are attached to the hyperbranched polymer molecules via the reducing end of the heparin moiety.
10. A process according to claim 1 wherein the hyperbranched polymer is selected from the group consisting of polyamidoamine, polypropyleneimine, polyethyleneimine and polyamine polymers and copolymers comprising one or more of polyamidoamine, polypropyleneimine, polyethyleneimine and polyamine hyperbranched polymers.
11. A process according to claim 1 wherein the functional end groups are primary amine groups.
12. A process according to claim 1 wherein the core moiety has a molecular weight of 50 to 130 Da.
13. A process according to claim 1 , wherein the hyperbranched polymer has a molecular weight of 25,000 to 200,000 Da.
14. A process according to claim 1 wherein the ratio of total molecular weight to core moiety molecular weight is at least 100:1.
15. A process according to claim 1 wherein the ratio of total molecular weight to core moiety molecular weight is between 200:1 and 5000:1.
16. A process according to claim 1 , wherein the layered coating comprises one or more coating bilayers of cationic polymer and anionic polymer, the innermost layer being a layer of cationic polymer.
17. A process according to claim 16 wherein the anionic polymer is an anionic polysaccharide.
18. A process according to claim 16 wherein the anionic polymer is a functionalized hyperbranched cationic polymer with a net negative charge.
19. A process according to claim 1 wherein the device is a medical device.
20. A process according to claim 1 wherein the layered coating of the device comprises one or more beneficial agents besides the anti-coagulant entities, selected from the group consisting of drug molecules and lubricious agents.
21. A process according to claim 7 wherein the heparin moieties are full length native heparin moieties or nitrous acid degraded heparin moieties.
22. A process according to claim 10 wherein the hyperbranched polymer is a polyamidoamine or a polyethyleneimine.