COMPOSITIONS AND METHODS FOR DELIVERY OF HYDROPHOBIC ACTIVE AGENTS

• US 20140336571A1
• Filed: 05/16/2014
• Published: 11/13/2014
• Est. Priority Date: 11/05/2012
• Status: Active Grant

• Current Assignee: Surmodics Incorporated
• Original Assignee: Surmodics Incorporated
• Inventors: Slager, Joram, Swan, Dale G., DuMez, Darin, Ventura, Joseph, Wadman, Shannon, McGonigle, Joseph Schmidt, Hergenrother, Robert W.
• Granted Patent: US 11,246,963 B2
• Time in Patent Office: Days
• US Class Current: 604/95.03
• CPC Class Codes: A61K 31/337 having four-membered rings, e.g. taxol
• CPC Class Codes: A61K 31/436 the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
• 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: A61L 2300/416 Anti-neoplastic or anti-proliferative or anti-restenosis or anti-angiogenic agents, e.g. paclitaxel, sirolimus
• CPC Class Codes: A61L 2300/62 Encapsulated active agents, e.g. emulsified droplets
• CPC Class Codes: A61L 2300/63 Crystals
• CPC Class Codes: A61L 2400/06 Flowable or injectable implant compositions
• CPC Class Codes: A61L 2420/06 Coatings containing a mixture of two or more compounds
• CPC Class Codes: A61L 2420/08 Coatings comprising two or more layers
• CPC Class Codes: A61L 29/041 obtained by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 29/085 Macromolecular materials
• CPC Class Codes: A61L 29/16 Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence
• CPC Class Codes: A61M 2025/105 having a balloon suitable for drug delivery, e.g. by using holes for delivery, drug coating or membranes
• CPC Class Codes: A61M 25/10 Balloon catheters A61M25/0125 takes precedence; embolectomy A61B17/22032; retractors A61B17/02; inflatable balloons for placing stents or stent-grafts A61F2/958 ; stomach balloons for treatment of obesity A61F5/0003; oesophagal tubes A61J15/00
• 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 an embodiment, the invention includes a drug delivery device including a substrate; and coated therapeutic agent particles disposed on the substrate, the coated therapeutic agent particles comprising a particulate hydrophobic therapeutic agent; and a vinyl amine polymer. Methods of making the delivery composition, as well as kits and methods of use are also included herein.

Claims

1. A drug delivery device comprising:

a substrate;

a hydrophilic polymer layer disposed on the substrate; and

coated therapeutic agent particles disposed on the hydrophilic polymer layer, the coated therapeutic agent particles comprising

a particulate hydrophobic therapeutic agent; and

a vinyl amine polymer component.

2. The drug delivery device of claim 1, the vinyl amine polymer component comprising poly(N-vinyl amine) (pNVA).

3. The drug delivery device of claim 1, the vinyl amine polymer component comprising a copolymer including N-vinyl amine subunits.

4. The drug delivery device of claim 1, the vinyl amine polymer component comprising a copolymer including N-vinyl amine and an accessory subunit, the accessory subunit selected from the group consisting of vinyl esters, (meth)acrylate esters, vinyl imidazoles, vinyl pyridines, vinyl alcohols, vinyl halides, acrylonitriles, acrylamides, vinyl silanes, styrenes and 1-vinyl-2-pyrrolidone.

5. The drug delivery device of claim 4, the accessory subunit comprising 1-vinyl-2-pyrrolidone.

6. The drug delivery device of claim 1, the vinyl amine polymer component comprising a terpolymer including N-vinyl amine, N-vinyl formamide, and an accessory subunit, the accessory subunit selected from the group consisting of vinyl esters, (meth)acrylate esters, vinyl imidazoles, vinyl pyridines, vinyl alcohols, vinyl halides, acrylonitriles, acrylamides, vinyl silanes, styrenes and 1-vinyl-2-pyrrolidone.

7. The drug delivery device of claim 1, the vinyl amine polymer component comprising hydrolyzed N-vinyl formamide, wherein the N-vinyl formamide is at least 50% hydrolyzed.

8. The drug delivery device of claim 1, further comprising an additive disposed between the coated therapeutic agent particles, the additive selected from the group consisting of saccharides and amphiphilic compounds

9. The drug delivery device of claim 8, the additive selected from the group consisting of glycogen, dextran, and non-ionic co-polymer of ethylene and propylene oxide.

10. The drug delivery device of claim 1, further comprising an additive disposed between the coated therapeutic agent particles, the additive selected from the group consisting of polyethylene glycol and derivatives thereof, polyvinyl pyrrolidone and derivatives thereof, polyvinyl alcohol and derivatives thereof, polyoxazolines, and poloxamers.

11. The drug delivery device of claim 1, the coated therapeutic agent particles exhibiting a Zeta potential of greater than +10 mV.

15. The drug delivery device of claim 1, the particulate hydrophobic therapeutic agent having an average diameter of between 100 nm and 10 μ

m.

16. The drug delivery device of claim 1, the particulate hydrophobic therapeutic agent having an average diameter of between 0.3 μ

m to about 1 μ

m.

19. The drug delivery device of claim 1, the particulate hydrophobic therapeutic agent selected from the group consisting of paclitaxel, sirolimus, and analogs thereof.

22. The drug delivery device of claim 1, the hydrophilic polymer layer covalently bonded to the substrate.

23. The drug delivery device of claim 1, the hydrophilic polymer layer cross-linked with a photoactivatable cross-linking agent.

24. The drug delivery device of claim 1, the device comprising a drug-containing balloon catheter.

12-14. -14. (canceled)

17-18. -18. (canceled)

20-21. -21. (canceled)

25. A drug delivery coating comprising

a polymeric layer, the polymeric layer comprising a hydrophilic surface;

coated therapeutic agent particles disposed on the hydrophilic surface, the coated therapeutic agent particles comprising

a particulate hydrophobic therapeutic agent core; and

a vinyl amine polymer component.

26-48. -48. (canceled)

49. A medical device comprising:

a capsule housing;

control circuitry disposed with in the capsule housing;

at least one moveable element operably connected to the capsule housing, the moveable element comprising

a substrate and

a coating disposed on the substrate, the coating comprising;

a hydrophilic polymer layer disposed on the substrate; and

coated therapeutic agent particles disposed on the hydrophilic polymer layer, the coated therapeutic agent particles comprising

a particulate hydrophobic therapeutic agent; and

a vinyl amine polymer component.

50. The medical device of claim 49, the control circuitry configured to cause the moveable element to move between a deployed position and a non-deployed position;

the medical device comprising a total width, wherein the total width of the medical device is greater in the deployed configuration than in the non-deployed configuration.

51-57. -57. (canceled)