Apparatus and methods for loading a drug eluting medical device

• US 8,632,846 B2
• Filed: 09/17/2010
• Issued: 01/21/2014
• Est. Priority Date: 09/17/2010
• Status: Active Grant

• Current Assignee: Medtronic Vascular, Inc. (Medtronic Plc)
• Original Assignee: Medtronic Vascular, Inc. (Medtronic Plc)
• Inventors: Avelar, Salvador, Mitchell, James
• Primary Examiner(s): SELLMAN, CACHET I
• Application Number:
  US12/884,578
• Publication Number:
  US 20120070562A1
• Time in Patent Office: 1,222 Days
• Field of Search: 427/2.1, 427/2.24, 427/2.25, 427/430.1, 427/346, 427/398.1, 623/1.1, 623 142- 148, 141/1, 141/18
• US Class Current: 427/2.24
• CPC Class Codes: A61F 2/86 Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure
• 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 2300/416 Anti-neoplastic or anti-proliferative or anti-restenosis or anti-angiogenic agents, e.g. paclitaxel, sirolimus
• CPC Class Codes: A61L 2300/802 Additives, excipients, e.g. cyclodextrins, fatty acids, surfactants
• CPC Class Codes: A61L 31/14 Materials characterised by their function or physical properties , e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: A61P 31/04 Antibacterial agents

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 loading a therapeutic substance within a hollow stent, the method comprising the steps of:

filling a lumenal space defined by a hollow wire that forms the hollow stent substantially full of a solution of a therapeutic substance and a solvent via a plurality of side openings within the hollow wire that forms the hollow stent until the lumenal space is substantially full of the solution to create a filled hollow stent;

loading the filled hollow stent into a processing chamber having an inert gas environment above atmospheric pressure in order to minimize evaporation of the solvent during loading;

closing the processing chamber to atmosphere and controlling a temperature and pressure of the processing chamber to precipitate the therapeutic substance out of solution within the lumenal space of the filled hollow stent without removal of the solvent and such that the solvent remains in a liquid phase;

cooling the filled hollow stent to a temperature below the melting point of the solvent such that the solvent freezes; and

sublimating the frozen solvent to extract substantially all residual solvent from the lumenal space of the filled hollow stent while the precipitated therapeutic substance remains therein to thereby load the hollow stent with the therapeutic substance for subsequent delivery within a body lumen.

2. The method of claim 1, wherein the step of precipitating the therapeutic substance includes reducing a temperature below ambient.

3. The method of claim 2, wherein the step of precipitating the therapeutic substance also includes reducing a pressure of the processing chamber below ambient.

4. The method of claim 2, wherein the step of precipitating the therapeutic substance further includes applying vibratory energy to the filled hollow stent.

5. The method of claim 2, wherein the step of sublimating includes utilizing a strong vacuum within the processing chamber to sublimate the frozen solvent.

6. The method of claim 2, wherein the 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 sublimation of the frozen solvent therefrom.

7. The method of claim 6, wherein the excipient is a hydrophilic agent.

8. The method of claim 7, wherein the high capacity solvent is tetrahydrofuran, the therapeutic substance is sirolimus and the excipient is urea.

9. The method of claim 6, wherein the excipient is a surfactant.

10. The method of claim 9, wherein the high capacity solvent is dichloromethane, the therapeutic substance is sirolimus and the excipient is a cyclodextrin.

11. The method of claim 2, wherein the 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 sublimation of the frozen solvent therefrom.

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

13. The method of claim 12, wherein the low capacity solvent is methanol, the therapeutic substance is sirolimus and the excipient is a cyclodextrin.

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

15. The method of claim 14, wherein the low capacity solvent is methanol, the therapeutic substance is sirolimus and the excipient is urea.