POLYMERS FOR REVERSING HEPARIN-BASED ANTICOAGULATION

• US 20180214478A1
• Filed: 02/02/2018
• Published: 08/02/2018
• Est. Priority Date: 06/01/2011
• Status: Active Grant

• Current Assignee: University of British Columbia
• Original Assignee: University of British Columbia
• Inventors: Kizhakkedathu, Jayachandran N., Shenoi, Rajesh A., Carter, Cedric J., Brooks, Donald E.
• Granted Patent: US 10,441,606 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 31/765 Polymers containing oxygen
• CPC Class Codes: A61K 31/785 Polymers containing nitrogen
• CPC Class Codes: A61K 31/795 Polymers containing sulfur
• CPC Class Codes: A61K 47/34 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers A61K47/10 takes precedence
• CPC Class Codes: A61K 9/0014 Skin, i.e. galenical aspects of topical compositions non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00
• CPC Class Codes: A61K 9/06 Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels composition of ointments, creams or gels A61K47/00
• CPC Class Codes: A61M 1/3675 Deactivation
• CPC Class Codes: A61M 1/3679 by absorption A61M1/3675 takes precedence
• CPC Class Codes: A61M 2202/0021 removed from and reintroduced into the body, e.g. after treatment
• CPC Class Codes: A61M 2202/0413 Blood
• CPC Class Codes: A61M 2202/0478 Heparin
• CPC Class Codes: B01D 15/36 involving ionic interaction
• CPC Class Codes: C08G 2340/00 Filter material
• CPC Class Codes: C08G 73/024 Polyamines containing oxygen in the form of ether bonds in the main chain
• CPC Class Codes: C08L 71/02 Polyalkylene oxides

Abstract

Embodiments presented herein relate to various polymers. Some of the polymer embodiments are heparin binding polymers. Some embodiments of the heparin binding polymers can be employed to bind to heparin for methods such as separating, purifying, removing, and/or isolating heparin and heparin like molecules.

Claims

1. A method of counteracting heparin in a subject, the method comprising:

administering a heparin binding polymer to the subject, wherein the heparin binding polymer comprises;

a core unit, wherein the core unit comprises a C_1-18 alkyl substituted with three or more of —

OR¹,

wherein each R¹ is independently selected from a polymer segment having monomer units of Formula (III);

2. The method of claim 1, wherein the core unit is a compound of Formula (V):

3. The method of claim 1, wherein the cationic moiety is an amine group.

4. The method of claim 3, wherein the wherein the amine group is a tetra-amine group, a hexa-amine group, or a deca-amine group.

5. The method of claim 1, wherein the cationic moiety is selected from at least one of the group consisting of:

Formula (VI), Formula (VII), and Formula (VIII);

6. The method of claim 1, wherein the cationic moiety comprises Formula (VI):

and wherein the heparin binding polymer comprises an average of 4 to 100 cationic moieties.

7. The method of claim 1, wherein the polymer segment of Formula (IV):

8. The method of claim 1, wherein at least one polymer segment of Formula (IV):

9. The method of claim 7, wherein the heparin binding polymer has a degree of PEGylation from about 5% to about 75%.

10. The method of claim 6, wherein the heparin binding polymer has a degree of PEGylation from about 20% to about 40%.

11. The method of claim 1, wherein the heparin binding polymer comprises 4 to 23 cationic moieties.

12. The method of claim 1, wherein the heparin binding polymer comprises an average of 4, 5, 16, 20, 24, 23, 8, 11, 16, or 36 cationic moieties.

13. The method of claim 1, wherein the heparin binding polymer has 16 to 92 cationic charges.

14. The method of claim 1 further comprising identifying a subject who has received an excess amount of heparin, wherein the identifying occurs before the heparin binding polymer is administered to the subject.

15. The method of claim 1, wherein the heparin binding polymer is administered subcutaneously.

16. The method of claim 1, wherein the heparin binding polymer is administered intravenously.

17. The method of claim 1, wherein the heparin binding polymer binds to heparin selected from at least one of:

unfractionated heparin (UFH), low molecular weight heparin (LMWH), ultra-low molecular weight heparin (ULMWH), fondaparinux, idraparinux enoxaparin, dalteparin, tinzaparin, semuloparin, or heparinoid.

18. A method of counteracting heparin in a subject, the method comprising:

administering a heparin binding polymer to the subject, wherein the heparin binding polymer comprises;

a core unit, wherein the core unit comprises a C_1-18 alkyl substituted with three or more of —

OR¹,

wherein each R¹ is independently selected from a polymer segment having monomer units of Formula (III);

19. The method of claim 18, wherein the core unit is a compound of Formula (V):

20. The method of claim 18, wherein the polymer segment of Formula (IV):

21. The method of claim 18, wherein at least one polymer segment of Formula (IV):

22. The method of claim 21, wherein the heparin binding polymer has a degree of PEGylation from about 20% to about 40%.

23. The method of claim 18, further comprising identifying a subject who has received an excess amount of heparin, wherein the identifying occurs before the heparin binding polymer is administered to the subject.

24. The method of claim 18, wherein the heparin binding polymer is administered subcutaneously.

25. The method of claim 18, wherein the heparin binding polymer is administered intravenously.

26. The method of claim 18, wherein the heparin binding polymer binds to heparin selected from at least one of:

unfractionated heparin (UFH), low molecular weight heparin (LMWH), ultra-low molecular weight heparin (ULMWH), fondaparinux, idraparinux enoxaparin, dalteparin, tinzaparin, semuloparin, or heparinoid.