Methods of drug loading a hollow stent with a high viscosity formulation

• US 8,927,047 B2
• Filed: 02/25/2011
• Issued: 01/06/2015
• Est. Priority Date: 02/25/2011
• Status: Expired due to Fees

• Current Assignee: Abbott Cardiovascular Systems Incorporated (Abbott Laboratories)
• Original Assignee: Abbott Cardiovascular Systems Incorporated (Abbott Laboratories)
• Inventors: Pacetti, Stephen D.
• Primary Examiner(s): Yuan, Dah-Wei D
• Assistant Examiner(s): Zhang, Diane
• Application Number:
  US13/035,803
• Publication Number:
  US 20120216905A1
• Time in Patent Office: 1,411 Days
• Field of Search: 427/2.1, 600/585, 623/1.11
• US Class Current: 427/2.1
• 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 31/082 Inorganic materials
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: C08L 67/04 Polyesters derived from hydroxycarboxylic acids, e.g. lactones C08L67/06 takes precedence

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 composition may include a therapeutic agent. In some embodiments, the composition has characteristics such that at a temperature of 20° C. to 30° C. and a pressure of one atmosphere, the viscosity of the composition is about 10 cP or greater than 10 cP.

Claims

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

providing a stent having 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, and the structural element comprising holes;

injecting a composition into the opening to fill the lumen, wherein 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 about 10 cP or greater than 10 cP; and

additionally comprising masking at least some of the holes to prevent the composition from escaping out of the holes during the injection process and optionally some time subsequent to the injection process;

wherein the holes of the structural element allow discharge of the composition from the structural element after implantation of the stent.

2. The method of claim 1, wherein 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 not less than 100 cP.

3. The method of claim 2, wherein 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 not less than 5,000 cP.

4. The method of claim 1, wherein the composition has a fluid consistency during the injection process.

5. The method of claim 1, wherein the composition has a gel-like consistency during the injection process.

6. The method of claim 1, wherein the composition is injected at an injection pressure of 10 to 15,000 lb/in².

7. The method of claim 1, wherein the temperature of the composition is between 20°

C. to 30°

C. during the injection process and the process in conducted at about one atmosphere.

8. The method of claim 1, wherein the composition comprises a therapeutic agent and an excipient.

9. The method of claim 8, wherein the therapeutic agent is selected from the group consisting of paclitaxel, protaxel, clobetasol, dexamethasone, momentasone, dexamethasone acetate, zotarolimus, sirolimus, everolimus, biolimus, ridaforolimus, novolimus, myolimus, temsirolimus, and all combinations thereof in all proportions.

10. The method of claim 8, wherein the therapeutic agent is dispersed in the excipient.

11. The method of claim 8, wherein the excipient is a non-volatile excipient.

12. The method of claim 8, wherein the excipient is selected from the group consisting of triglycerides, diglycerides, monoglycerides, fatty alcohols, liquid poloxamers, polysorbate 20, polysorbate 80, polyethylene glycols of a number average molecular weight of less than or equal to 1000 Daltons, propylene glycol, dimethyl sulfoxide, glycerol, benzyl benzoate, benzyl alcohol, N-methyl pyrrolidone, and all combinations thereof in all proportions.

13. The method of claim 8, wherein the composition comprises microspheres, nanoparticles, microparticles, microshells, or a combination thereof which comprise the therapeutic agent.

14. The method of claim 13, wherein the composition comprises microspheres, the microspheres comprising the therapeutic agent and another material.

15. The method of claim 8, wherein the composition injected into the structural element of the stent provides for a sustained release of the therapeutic agent once the stent is implanted in-vivo, wherein the sustained release is not more than 80% of the therapeutic agent is released within the first 12 hours post implantation.

16. The method of claim 15, wherein the sustained release is not more than 80% of the therapeutic agent is released within the first 24 hours post implantation.

17. The method of claim 8, wherein the composition comprises at least one excipient selected from the group consisting of triglycerides, diglycerides, monoglycerides, fatty alcohols, liquid poloxamers, propylene glycol, dimethyl sulfoxide, glycerol, benzyl benzoate, benzyl alcohol, and N-methyl pyrrolidone.

18. The method of claim 1, further comprising heating the structural element, the composition, or both to a temperature greater than 20°

C. prior to injection of the composition.

19. The method of claim 1, wherein the temperature of the structural element, the composition, or both are maintained at a temperature greater than 20°

C. during the injection of the composition.

20. The method of claim 1, wherein the temperature of the structural element, the composition, or both are maintained between 20°

C. to 30°

C. during the injection of the composition.

21. The method of claim 20, further comprising cooling the composition that has been injected after the injection process has been completed.

22. The method of claim 1, wherein the temperature of the structural element, the composition, or both do not exceed 70°

C. during the injection of the composition.

23. 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 holes that allow discharge of the composition from the structural element after implantation of the stent comprise a plurality of discharge openings about a surface of the tube, wherein each of the discharge openings is at most 25% of the size of the access opening.

24. The method of claim 23, wherein at least some of the discharge openings are in fluid communication with each other through the lumen of the tube.

25. The method of claim 23, further comprising sealing the access opening once the injection process has been completed.

26. The method of claim 23, further comprising sealing the access opening after the injection process has been completed and after the composition is at a temperature of 25°

C. or less than 25°

C.

27. The method of claim 1, wherein the masking comprises disposing the stent or the structural element inside a sleeve followed by conforming the sleeve to at least the abluminal surface of the stent or the structural element by

(i) expanding the stent or the structural element;

(ii) applying pressure to the exterior of the sleeve;

(iii) pulling a vacuum inside of the sleeve;

or

(iv) a combination of two or more of (i) to (iii).

28. The method of claim 1, additionally comprising unmasking the holes after the temperature of the composition is at 25°

C. or less than 25°

C.

29. The method of claim 1, wherein the masking comprises applying a thin layer of a bioabsorbable coating that remains on the structural element for a time period subsequent to implantation of the stent in a patient.

30. The method of claim 29, wherein at a temperature of 20°

C. to 30°

C. and at a pressure of about one atmosphere, the composition is in a fluid state with a viscosity of not less than 10 cP and not more than 10,000 cP.

31. The method of claim 1, wherein the structural element is a tube, wherein the access opening is positioned at one end of the tube, the other end of the tube being either an open end or a closed end, and the method further comprising, after the injection process, sealing the access opening, and if the other end is an open end, additionally sealing the other end.

32. The method of claim 1, wherein the composition is free of, or essentially free of, solvents.