Methods of drug loading a hollow stent by immersion

• US 9,051,065 B2
• Filed: 03/18/2013
• Issued: 06/09/2015
• Est. Priority Date: 02/25/2011
• Status: Active Grant

• Current Assignee: Abbott Cardiovascular Systems Incorporated (Abbott Laboratories Incorporated)
• Original Assignee: Abbott Cardiovascular Systems Incorporated (Abbott Laboratories Incorporated)
• Inventors: Pacetti, Stephen D.
• Primary Examiner(s): SELLMAN, CACHET I
• Application Number:
  US13/846,711
• Publication Number:
  US 20130276412A1
• Time in Patent Office: 813 Days
• US Class Current: 1/1
• CPC Class Codes: A61F 2/91 made from perforated sheet material or tubes, e.g. perforated by laser cuts or etched holes
• 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 2300/43 Hormones, e.g. dexamethasone
• CPC Class Codes: A61L 2300/602 Type of release, e.g. controlled, sustained, slow
• CPC Class Codes: A61L 31/10 Macromolecular materials
• 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: A61L 33/00 Antithrombogenic treatment of surgical articles, e.g. sutures, catheters, prostheses, or of articles for the manipulation or conditioning of blood; Materials for such treatment
• CPC Class Codes: B05D 3/0218 Pretreatment, e.g. heating the substrate
• CPC Class Codes: B65B 3/003 Filling medical containers such as ampoules, vials, syringes or the like

Abstract

A method of loading a composition into a structural element of a stent, where the structural element is defined by a lumen and at least one opening to access the lumen. The structural element, or a stent having such a structural element, is immersed in a solution or a composition, and the composition or solution is allowed to fill the lumen. The composition or solution may comprise a therapeutic agent.

Claims

1. A method of loading a composition into a structural element of a stent, comprising:

providing a stent comprising a structural element or providing a structural element that is to be used in forming a stent, the structural element defined by a lumen and at least one opening to access the lumen;

providing a container filled with the composition, the composition comprising a therapeutic agent;

wherein

the composition is in a fluid state in the container, and the composition has characteristics such that when the composition is at a temperature of 30°

C. and at one atmosphere, the composition is in a solid state or semi-solid state or in a fluid state with a viscosity of about 10 cP or greater than 10 cP;

or

the composition has characteristics such that when the composition is at a temperature of 20°

C. to 30°

C. and a pressure of one atmosphere, the viscosity of the composition is greater than 10 cP or about 10 cP;

heating the structural element to a temperature of about 30°

C. to about 60°

C.;

after heating the structural element, immersing the structural element into the composition; and

allowing the composition to fill the lumen.

2. The method of claim 1, further comprising, after allowing the composition to fill the lumen, removing the structural element from the composition.

3. The method of claim 2, further comprising, sealing the access opening when the structural element is removed from the composition to prevent the composition from escaping out from the lumen.

4. The method of claim 1, further comprising rinsing the structural element to at least partially remove the composition comprising the therapeutic agent on an outer surface of the structural element such that the rinsing act does not remove the composition comprising the therapeutic agent from within the lumen.

5. The method of claim 1, wherein the structural element is a tube such that the access opening is positioned at one end of the tube and the tube further comprises a plurality of discharge openings about a surface of the tube to allow discharge of the composition comprising the therapeutic agent from the structural element after implantation of the stent in a patient.

6. The method of claim 5, additionally comprising, prior to the immersion, attaching a conduit to the access opening, and applying a vacuum through the access opening via the conduit when the structural element is immersed in the composition to draw the composition through the discharge openings into the lumen.

7. The method of claim 5, wherein each of the discharge openings is at most 50% of the size of the access opening.

8. The method of claim 1, wherein the composition is free of, or essentially free of, solvents, and the composition is in a fluid state in the container, and the composition has characteristics such that when the composition is at a temperature of 30°

C. and at one atmosphere, the composition is in a solid state or a semi-solid state or in a fluid state with a viscosity of about 10 cP or greater than 10 cP.

9. The method of claim 8, wherein the composition consists essentially of the therapeutic agent.

10. The method of claim 9, wherein the therapeutic agent is relatively stable or stable when melted.

11. The method of claim 9, wherein the therapeutic agent is selected from the group consisting of paclitaxel, protaxel, dexamethasone, momentasone, clobetasol, dexamethasone acetate, and all combinations thereof in all proportions.

12. The method of claim 1, further comprising, after allowing the composition to fill the lumen, cooling the structural element.

13. The method of claim 12, wherein the therapeutic agent is temperature sensitive.

14. The method of claim 12, wherein the therapeutic agent is not stable at temperatures of about 60°

C. and greater than 60°

C.

15. The method of claim 12, wherein the therapeutic agent is selected from the group consisting of zotarolimus, everolimus, sirolimus, biolimus, ridaforolimus, novolimus, myolimus, temsirolimus, and all combinations thereof in all proportions.

16. The method of claim 12, wherein the excipient is selected from the group consisting of solid poloxamers, polysorbate 60, Vitamin E TGPS, di-block and tri-block polymers formed from ethylene oxide and propylene oxide, Poloxamer 188, Poloxamer 407, ascorbyl palmitate, lecithin, egg yolk phospholipid, phosphatidylcholine, polyethylene glycol-phosphatidyl ethanolamine conjugate (PEG-PE), polyethylene glycol, triglycerides, diglycerides, monoglycerides, fatty alcohols, and all combinations thereof in all proportions.

17. The method of claim 1, wherein the composition is free of, or essentially free of, solvents, and the composition is in a fluid state in the container, and the composition has characteristics such that when the composition is at a temperature of 30°

C. and at one atmosphere, the composition is in a solid state or a semi-solid state or in a fluid state with a viscosity of not less than 100 cP.

18. The method of claim 1, wherein the composition is free of, or essentially free of, solvents, and the composition is in a fluid state in the container, and the composition has characteristics such that when the composition is at a temperature of 30°

C. and at one atmosphere, the composition is in a solid state or a semi-solid state.

19. The method of claim 18, wherein the composition comprises an excipient.

20. The method of claim 19, wherein the therapeutic agent is dispersed in the excipient.

21. The method of claim 19, wherein the composition comprises microspheres, nanoparticles, microparticles, microshells, or a combination thereof which comprise the therapeutic agent.

22. The method of claim 1, further comprising after allowing the composition to fill the lumen, cooling the structural element.

23. The method of claim 1, wherein the composition is free of, or essentially free of, solvents, and the composition has characteristics such that when the composition is at a temperature of 20°

C. to 30°

C. and a pressure of one atmosphere, the viscosity of the composition is greater than 100 cP or about 100 cP.