Aldehyde-fixed, dried platelets with covalently attached exogenous active agent and method of making thereof

• US 8,492,081 B2
• Filed: 09/28/2007
• Issued: 07/23/2013
• Est. Priority Date: 05/16/2003
• Status: Expired due to Fees

• Current Assignee: University of North Carolina At Chapel Hill (University of North Carolina System)
• Original Assignee: University of North Carolina At Chapel Hill (University of North Carolina System)
• Inventors: Nichols, Timothy C., Fischer, Thomas, Read, Marjorie S.
• Primary Examiner(s): SAUCIER, SANDRA E
• Application Number:
  US11/863,462
• Publication Number:
  US 20120128647A1
• Time in Patent Office: 2,125 Days
• Field of Search: None
• US Class Current: 435/2
• CPC Class Codes: A01N 1/02 Preservation of living parts
• CPC Class Codes: A01N 1/0215 Disinfecting agents, e.g. antimicrobials for preserving living parts
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/7088 Compounds having three or more nucleosides or nucleotides
• CPC Class Codes: A61K 35/18 Erythrocytes haemoglobin A61K38/42
• CPC Class Codes: A61K 35/19 Platelets; Megacaryocytes
• CPC Class Codes: A61K 38/02 Peptides of undefined number of amino acids; Derivatives thereof
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/6901 Conjugates being cells, cell fragments, viruses, ghosts, red blood cells or viral vectors
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 7/04 Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
• CPC Class Codes: Y10S 977/905 Specially adapted for travel through blood circulatory system

Abstract

Fixed-dried blood cells carrying an active agent are described, along with methods of making the same, methods of using the same, and compositions containing the same. The blood cells are preferably blood platelets.

Claims

1. Aldehyde-fixed, dried, mammalian platelets carrying an exogenous active agent,

wherein said exogenous active agent is selected from the group consisting of diagnostic agents and therapeutic agents and is covalently coupled to the interior of said aldehyde-fixed, dried, mammalian platelets, and

wherein said aldehyde-fixed, dried, mammalian platelets, upon reconstitution, adhere to thrombogenic surfaces, undergo shape change upon adhering to a thrombogenic surface, and lead to the formation of a hemostatic plug upon adhering to a thrombogenic surface.

2. The aldehyde-fixed, dried, mammalian platelets of claim 1, wherein said aldehyde-fixed, dried, mammalian platelets comprise aldehyde-fixed, dried, human platelets.

3. The aldehyde-fixed, dried, mammalian platelets of claim 1, wherein, upon reconstitution, said aldehyde-fixed, dried mammalian platelets release their granular contents upon adhering to a thrombogenic surface.

4. The aldehyde-fixed, dried, mammalian platelets of claim 1, wherein said exogenous active agent comprises an antiviral agent.

5. The aldehyde-fixed, dried, mammalian platelets of claim 1, wherein said exogenous active agent comprises a blood coagulation protein.

6. The aldehyde-fixed, dried, mammalian platelets of claim 1, wherein said exogenous active agent comprises a blood anti-coagulation protein.

7. The aldehyde-fixed, dried, mammalian platelets of claim 1, wherein said exogenous active agent comprises a nucleic acid.

8. The aldehyde-fixed, dried, mammalian platelets of claim 1, wherein said exogenous active agent is selected from the group consisting of detectable compounds, antiviral agents, blood coagulation proteins, blood anti-coagulation protein, and nucleic acids.

9. The aldehyde-fixed, dried, mammalian platelets of claim 1, wherein said exogenous active agent is a detectable compound.

10. A pharmaceutical composition comprising:

a pharmaceutically acceptable carrier; and

aldehyde-fixed, dried, mammalian platelets having an exogenous active agent coupled thereto, said aldehyde-fixed, dried, mammalian platelets rehydrated in said pharmaceutically acceptable carrier,

wherein said exogenous active agent is selected from the group consisting of diagnostic agents and therapeutic agents and is covalently coupled to the interior of said aldehyde-fixed, dried, mammalian platelets, and

wherein said aldehyde-fixed, dried, mammalian platelets, upon reconstitution, adhere to thrombogenic surfaces, undergo shape change upon adhering to a thrombogenic surface, and lead to the formation of a hemostatic plug upon adhering to a thrombogenic surface.

11. The pharmaceutical composition of claim 10, wherein said carrier is a sterile carrier.

12. The pharmaceutical composition of claim 10, wherein said carrier is a solid carrier.

13. The pharmaceutical composition of claim 10, wherein said carrier is a liquid carrier.

14. The pharmaceutical composition of claim 10, wherein said carrier is an aqueous carrier.

15. The pharmaceutical composition of claim 10, wherein said aldehyde-fixed, dried, mammalian platelets comprise aldehyde-fixed, dried, human platelets.

16. The pharmaceutical composition of claim 10, wherein, upon reconstitution, said aldehyde-fixed, dried, mammalian platelets release their granular contents upon adhering to a thrombogenic surface.

17. The pharmaceutical composition of claim 10, wherein said exogenous active agent comprises an antiviral agent.

18. The pharmaceutical composition of claim 10, wherein said exogenous active agent comprises a blood coagulation protein.

19. The pharmaceutical composition of claim 10, wherein said exogenous active agent comprises a blood anti-coagulation protein.

20. The pharmaceutical composition of claim 10, wherein said exogenous active agent comprises a nucleic acid.

21. The pharmaceutical composition of claim 10, wherein said exogenous active agent is selected from the group consisting of detectable compounds, antiviral agents, blood coagulation proteins, blood anti-coagulation protein, and nucleic acids.

22. The pharmaceutical composition of claim 10, wherein said exogenous active agent is a detectable compound.

23. A method of making aldehyde-fixed, dried, mammalian platelets carrying an exogenous active agent, comprising:

providing aldehyde-fixed mammalian platelets;

coupling said exogenous active agent covalently to the interior of said aldehyde-fixed mammalian platelets; and

drying said aldehyde-fixed mammalian platelets to produce aldehyde-fixed, dried, mammalian platelets carrying said exogenous active agent;

wherein said exogenous active agent is selected from the group consisting of diagnostic agents and therapeutic agents, and

wherein said aldehyde-fixed, dried, mammalian platelets, upon reconstitution, adhere to thrombogenic surfaces, undergo shape change upon adhering to a thrombogenic surface, and lead to the formation of a hemostatic plug upon adhering to a thrombogenic surface.

24. The method of claim 23, wherein said aldehyde-fixed, dried, mammalian platelets carrying said exogenous active agent are rehydrated in a pharmaceutically acceptable carrier to provide a pharmaceutically acceptable composition comprising rehydrated aldehyde-fixed, dried, mammalian platelets carrying said exogenous active agent.

25. The method of claim 23, wherein said aldehyde-fixed mammalian platelets comprise aldehyde-fixed human platelets.

26. The method of claim 23, wherein, upon reconstitution, said rehydrated aldehyde-fixed, dried, mammalian platelets release their granular contents upon adhering to a thrombogenic surface.

27. The method according to claim 23, wherein said exogenous active agent is selected from the group consisting of detectable compounds, antiviral agents, blood coagulation proteins, blood anti-coagulation protein, and nucleic acids.

28. Aldehyde-fixed, dried, mammalian platelets carrying an exogenous active agent,

wherein said exogenous active agent is selected from the group consisting of diagnostic agents and therapeutic agents and is covalently coupled to the surface of said aldehyde-fixed, dried, mammalian platelets;

and

wherein said aldehyde-fixed, dried, mammalian platelets, upon reconstitution, adhere to thrombogenic surfaces, undergo shape change upon adhering to a thrombogenic surface, and lead to the formation of a hemostatic plug upon adhering to a thrombogenic surface.

29. The aldehyde-fixed, dried, mammalian platelets of claim 28, wherein said aldehyde-fixed, dried mammalian blood cells comprise aldehyde-fixed, dried, human blood cells.

30. The aldehyde-fixed, dried, mammalian platelets of claim 28, wherein said aldehyde-fixed, dried, mammalian platelets, upon reconstitution, release their granular contents upon adhering to a thrombogenic surface.

31. The aldehyde-fixed, dried, mammalian platelets of claim 28, wherein said exogenous active agent comprises an antiviral agent.

32. The aldehyde-fixed, dried, mammalian platelets of claim 28, wherein said exogenous active agent comprises a blood coagulation protein.

33. The aldehyde-fixed, dried, mammalian platelets of claim 28, wherein said exogenous active agent comprises a blood anti-coagulation protein.

34. A pharmaceutical composition comprising:

a pharmaceutically acceptable carrier; and

the aldehyde-fixed, dried, mammalian platelets of claim 28, said aldehyde-fixed, dried, mammalian platelets rehydrated in said pharmaceutically acceptable carrier.

35. The pharmaceutical composition of claim 34, wherein said aldehyde-fixed, dried, mammalian platelets, upon reconstitution, release their granular contents upon adhering to a thrombogenic surface.