Apparatus and Methods for Loading a Drug Eluting Medical Device

• US 20110070357A1
• Filed: 09/17/2010
• Published: 03/24/2011
• Est. Priority Date: 09/20/2009
• Status: Active Grant

• Current Assignee: Medtronic Vascular, Inc. (Medtronic Plc)
• Original Assignee: Medtronic Vascular, Inc. (Medtronic Plc)
• Inventors: Silver, Michele, Chu, Dishuan, Mitchell, James E., Avelar, Salvador, Traina, Joseph, Peterson, Justin
• Granted Patent: US 8,460,745 B2
• Time in Patent Office: Days
• US Class Current: 427/2.25
• CPC Class Codes: A61F 2240/001 Designing or manufacturing processes
• CPC Class Codes: A61F 2250/0068 the pharmaceutical product being in a reservoir
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence

Abstract

Methods and apparatus are disclosed for loading a therapeutic substance or drug within a lumenal space of a hollow wire having a plurality of side openings along a length thereof that forms a hollow drug-eluting stent with a plurality of side drug delivery openings. Loading a drug within the lumenal space of the hollow stent includes a drug filling step, in which the drug is mixed with a solvent or dispersion medium. The lumenal space may be filled with the drug solution or suspension in a reverse fill process and/or a forward fill process. After the drug filling step, a solvent or dispersion medium extracting step is performed to extract the solvent or dispersion medium from within the lumenal space such that only the drug remains within the hollow stent. A stent cleaning step may be performed to an exterior surface of the hollow stent.

Claims

1. A method of reverse loading a therapeutic substance within a lumenal space of a hollow wire having a plurality of side openings that forms a hollow stent for drug elution, the method comprising the steps of:

preparing a suspension or solution of the therapeutic substance;

submerging the hollow stent within the solution or suspension; and

applying a vacuum to a first open end of the hollow stent that is connected to the lumenal space to draw the solution or suspension into the lumenal space of the hollow stent via at least the plurality of side openings.

2. The method of claim 1, wherein the step of submerging includes attaching the first open end of the hollow stent to a manifold that is coupled to a vacuum source and positioning the hollow stent within a reservoir that holds the solution or suspension such that at least a portion of the hollow stent that includes the plurality of side openings is submerged within the solution or suspension therein.

3. The method of claim 2, wherein a plurality of hollow stents are attached by first open ends thereof to the manifold and are positioned within the reservoir such that at least respective portions of the hollow stents that include the plurality of side openings are submerged in the solution or suspension therein.

4. The method of claim 1, wherein the step of submerging includes placing the hollow stent within a pressure chamber with the therapeutic substance in suspension and attaching the first open end of the hollow stent to a first vacuum source and attaching an opposing second open end of the hollow stent to a second vacuum source.

5. The method of claim 4, wherein the step of applying a vacuum includes simultaneously operating the first and second vacuum sources to pull a vacuum that draws the therapeutic substance in suspension into the lumenal space of the hollow stent via the plurality of side openings.

6. The method of claim 5, further comprising:

pressurizing the pressure chamber to greater than ambient pressure to force the therapeutic substance in suspension into the lumenal space of the hollow stent via the plurality of side openings, such that the step of applying a vacuum aids in drawing the therapeutic substance in suspension into the lumenal space via the plurality of side openings and outward through the lumenal space towards respective first and second open ends of the hollow stent.

7. The method of claim 6, further comprising:

using a filtering means at each of the first and second open ends of the hollow stent to prevent solid particles of the therapeutic substance from passing therethrough while permitting a dispersion medium of the suspension to pass such that the therapeutic substance packs within the lumenal space of the hollow stent.

8. The method of claim 1, wherein the therapeutic substance is in suspension and a dispersion medium of the suspension is selected from the group consisting of water and C5-C10 alkanes and the suspension also includes surfactants to stabilize dispersion of the therapeutic substance within the suspension.

9. The method of claim 8, wherein the dispersion medium is water, the surfactant is a polysorbate, and the therapeutic substance is sirolimus.

10. The method of claim 8, wherein the dispersion medium is hexane, the surfactant is a sorbitan fatty acid ester, and the therapeutic substance is sirolimus.

11. The method of claim 1, wherein the therapeutic substance is in solution and a solvent of the solution is a high-capacity solvent and the solution also includes an excipient to assist in elution of the therapeutic substance, wherein the excipient and therapeutic substance remain within the hollow stent after extraction of residual solvent therefrom.

12. The method of claim 11, wherein the excipient is a hydrophilic agent.

13. The method of claim 12, wherein the high capacity solvent is tetrahydrofuran, the therapeutic substance is sirolimus and the excipient is urea.

14. The method of claim 11, wherein the excipient is a surfactant.

15. The method of claim 14, wherein the high capacity solvent is DCM, the therapeutic substance is sirolimus and the excipient is a cyclodextrin.

16. The method of claim 1, wherein the therapeutic substance is in solution and a solvent of the solution is a low-capacity solvent and the solution also includes an excipient to assist in elution of the therapeutic substance, wherein the excipient and therapeutic substance remain within the hollow stent after extraction of residual solvent therefrom.

17. The method of claim 16, wherein the excipient is a surfactant.

18. The method of claim 17, wherein the low capacity solvent is methanol, the therapeutic substance is sirolimus and the excipient is a cyclodextrin.

19. The method of claim 16, wherein the excipient is a hydrophilic agent.

20. The method of claim 19, wherein the low capacity solvent is methanol, the therapeutic substance is sirolimus and the excipient is urea.