Methods of loading a hollow stent with a drug or drug formulation

• US 10,155,599 B2
• Filed: 12/01/2014
• Issued: 12/18/2018
• 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, Hai Y
• Application Number:
  US14/557,057
• Publication Number:
  US 20150083272A1
• Time in Patent Office: 1,478 Days
• Field of Search: 427 225, 427 214, 427 228, 427 23, 623 115, 623 113, 623 142
• 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: 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 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• 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: 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 composition may comprise a therapeutic agent, and wherein at a temperature of 30° C. and at one atmosphere, the composition may be in a solid state or semi-solid state.

Claims

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

providing a stent having a structural element, the structural element defined by a lumen and at least one opening to access the lumen, and the structural element further comprising holes and/or pores to access the lumen, and the access opening optionally being one of the holes and/or pores;

injecting a composition in a fluid state into the opening to load the lumen with the composition, wherein the composition comprises a therapeutic agent, and wherein the composition has characteristics such that at a temperature of 30°

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

additionally comprising masking at least some of the holes and/or pores prior to the injection to prevent the composition from escaping out of the holes and/or pores during the injection process and optionally some time subsequent to the injection process, the masking comprising positioning a removable sleeve over at least some of the holes and/or pores and the masking also comprising pressurizing or shrinking the removable sleeve onto the stent;

wherein the holes and/or pores allow discharge of the composition out from the structural element after implantation of the stent;

wherein the removable sleeve has an inner diameter greater than the outer diameter of the stent; and

wherein the removable sleeve comprises one or more silicones, one or more polyurethanes, one or more styrene-isobutylene styrene triblock polymers, one or more thermoplastic polyester elastomers, one or more poly(ether urea urethanes), one or more poly(ester urethanes), one or more poly(carbonate urethanes), poly(tetramethylene glycol-co-butanediol-co-toluene diisocyanate), poly(dimethyl siloxane), one or more thermoplastic elastomer nylon copolymers, one or more polyether block amide thermoplastic elastomers, crosslinked polyethylene, or a combination thereof.

2. The method of claim 1, wherein the composition has characteristics such that at a temperature of 30°

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

3. 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 and/or pores which allow discharge of the composition out from the structural element after implantation of the stent comprise a network of discharge openings about a surface of the tube, wherein each of the discharge openings is at most 50% of the size of the access opening.

4. The method of claim 3, wherein at least some of the discharge openings are in fluid communication with each other through the lumen.

5. The method of claim 3, further comprising sealing the access opening once the injection process is completed.

6. The method of claim 3, wherein the surface is an outer tissue contacting surface of the stent.

7. The method of claim 1, wherein the stent comprises an abluminal surface and the holes and/or pores are in the abluminal surface, and wherein positioning the removable sleeve over at least some of the holes and/or pores comprises disposing the stent inside the sleeve followed by pressurizing or shrinking the sleeve onto the stent by conforming the sleeve to the abluminal surface of the stent by

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

(ii) pulling a vacuum inside of the sleeve;

or

(iii) a combination of (i) and (ii).

8. The method of claim 1, additionally comprising unmasking the holes and/or pores after the temperature of the composition is at or below 30°

C.

9. 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, such that after the injection process the access opening is sealed, and if the other end is an open end, the other end is additionally sealed.

10. The method of claim 1, wherein the composition consists of the therapeutic agent, and the therapeutic agent comprises paclitaxel, protaxel, dexamethasone, momentasone, clobetasol, dexamethasone acetate, or a combination thereof in any proportions.

11. The method of claim 1, wherein the therapeutic agent comprises paclitaxel, protaxel, dexamethasone, momentasone, clobetasol, dexamethasone acetate, or a combination thereof in any proportions.

12. The method of claim 1, wherein the composition consists of the therapeutic agent.

13. The method of claim 12, wherein the composition is injected at an injection pressure of 10 to 10,000 lb/int.

14. The method of claim 1, wherein the composition comprises an excipient.

15. The method of claim 14, wherein the composition consists of the therapeutic agent and the excipient.

16. The method of claim 14, wherein the temperature of the structural element or the composition does not exceed 65°

C. during the injection of the composition.

17. The method of claim 14, wherein the therapeutic agent comprises zotarolimus, everolimus, sirolimus, biolimus, ridaforolimus, novolimus, myolimus, temsirolimus, or a combination thereof in any proportions.

18. The method of claim 14, wherein the excipient comprises one or more solid poloxamers, polysorbate 60, one or more triglycerides, one or more diglycerides, one or more monoglycerides, one or more fatty alcohols, Vitamin E TGPS, one or more di-block polymers formed from ethylene oxide and propylene oxide, one or more triblock 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, or any combination thereof in any proportions.

19. The method of claim 14, wherein the composition is injected at an injection pressure of 10 to 10,000 lb/in².

20. The method of claim 14, wherein the therapeutic agent is dispersed in the excipient.

21. The method of claim 20, wherein the composition comprises microspheres, nanoparticles, microparticles, microshells, or a combination thereof which comprise at least a portion of the therapeutic agent.

22. The method of claim 1, further comprising maintaining the temperature of the structural element above 25°

C. during the injection of the composition.

23. The method of claim 1, wherein the viscosity of the composition is 5 to 10,000 cP during the injection of the composition.

24. The method of claim 1, further comprising cooling the composition after the injection process is completed.

25. The method of claim 1 further comprising 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.

26. The method of claim 1, wherein the composition has characteristics such that at a temperature of 30°

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

27. The method of claim 1, wherein the composition is free of solvents.

28. The method of claim 27, wherein the composition consists of the therapeutic agent.

29. The method of claim 27, wherein the composition comprises an excipient.