COMPOSITION AND METHOD FOR DELIVERY OF HYDROPHOBIC ACTIVE AGENTS

• US 20140142166A1
• Filed: 11/05/2013
• Published: 05/22/2014
• Est. Priority Date: 11/05/2012
• Status: Active Grant

• Current Assignee: Surmodics Incorporated
• Original Assignee: Surmodics Incorporated
• Inventors: Wadman, Shannon, Slager, Joram, McGonigle, Joseph Schmidt, Hergenrother, Robert W., Ventura, Joseph
• Granted Patent: US 9,555,119 B2
• Time in Patent Office: Days
• US Class Current: 514/449
• CPC Class Codes: A61K 31/337 having four-membered rings, e.g. taxol
• 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 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/08 Solutions composition of solutions A61K47/00
• CPC Class Codes: A61L 2300/416 Anti-neoplastic or anti-proliferative or anti-restenosis or anti-angiogenic agents, e.g. paclitaxel, sirolimus
• CPC Class Codes: A61L 2300/63 Crystals
• CPC Class Codes: A61L 2400/06 Flowable or injectable implant compositions
• CPC Class Codes: A61L 27/18 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C08L 79/02 Polyamines

Abstract

Disclosed herein is a delivery composition for administering a hydrophobic active agent. In one embodiment, a delivery composition for local administration of a hydrophobic active agent to a tissue or organ of a patient is disclosed. In one embodiment, the delivery composition includes a cationic delivery agent, a therapeutically effective amount of a hydrophobic active agent and a pharmaceutically acceptable aqueous carrier. In one embodiment, the cationic delivery agent includes polyethyleneimine (PEI). In a more specific embodiment, the cationic delivery agent includes branched PEI. Methods of making the delivery composition, as well as kits and methods of use are also disclosed.

Claims

1. A delivery composition for local administration of a hydrophobic active agent, the delivery composition comprising:

a cationic delivery agent;

a therapeutically effective amount of the hydrophobic active agent; and

a pharmaceutically acceptable aqueous carrier.

2. The composition according to claim 1, wherein the cationic delivery agent comprises polyetheyleneimine (PEI).

3. The composition according to claim 2, wherein the cationic delivery agent comprises branched PEI.

4. The composition according to claim 3, wherein the branched PEI has a molecular weight of at least about 25 kD and up to about 5000 kD.

5. The composition according to claim 3, wherein the branched PEI has a molecular weight of at least about 100 kD and up to about 3000 kD.

7. The composition according to claim 3, wherein branched PEI has a ratio of primary:

secondary;

tertiary amines between about 1;

3;

1 and about 1;

1;

1.

8. The composition according to claim 3, wherein branched PEI has a ratio of primary:

secondary;

tertiary amines of between about 1;

2;

1 and about 1;

1;

1.

9. The composition according to claim 1, comprising cationic delivery agent:

hydrophobic active agent at a ratio of at least about 1;

1 and up to about 1;

25.

10. The composition according to claim 1, comprising cationic delivery agent:

hydrophobic active agent at a ratio of at least about 1;

2 and up to about 1;

20.

11. The composition according to claim 1, comprising cationic delivery agent:

hydrophobic active agent at a ratio of at least about 1;

5 and up to about 1;

10.

12. The composition according to claim 1, comprising at least about 1 mg/ml and up to about 25 mg/ml cationic delivery agent.

13. The composition according to claim 1, comprising at least about 5 mg/ml and up to about 125 mg/ml hydrophobic active agent.

14. The composition according to claim 1, wherein the aqueous carrier is selected from water and buffered saline.

15. The composition according to claim 1, comprising a pH between 5 and 9.

18. The composition according to claim 1, wherein the hydrophobic active agent is selected from an antiproliferative, analgesic, anti-inflammatory, anti-arrhythmic, anti-bacterial, anti-coagulant, anti-hypertensive, anti-muscarinic, anti-neoplastic, beta-blocker, cardiac inotropic agent, corticosteroids, lipid regulating agents, anti-anginal agents, and combinations thereof.

19. The composition according to claim 1, wherein the hydrophobic active agent comprises an antiproliferative selected from paclitaxel, sirolimus, everolimus, biolimus A9, zotarolimus, tacrolimus, and pimecrolimus and mixtures thereof.

6. (canceled)

16-17. -17. (canceled)

20-45. -45. (canceled)

46. A method for local administration of a therapeutically or prophylactically effective amount of a hydrophobic active agent to a tissue or organ of a patient, the method comprising:

preparing a composition comprising

a cationic delivery agent;

a therapeutically effective amount of the hydrophobic active agent; and

a pharmaceutically acceptable aqueous carrier; and

applying the composition to the tissue or organ of the patient.

63. The method of claim 46, wherein the cationic delivery agent comprises polyetheyleneimine (PEI).

64. The method of claim 63, wherein the PEI has a molecular weight of at least about 25 kD and up to about 5000 kD.

47-62. -62. (canceled)