Composition and method for making a biodegradable drug delivery stent

• US 5,980,551 A
• Filed: 02/07/1997
• Issued: 11/09/1999
• Est. Priority Date: 02/07/1997
• Status: Expired due to Fees

• Current Assignee: Endovasc Ltd., Inc.
• Original Assignee: Endovasc Ltd., Inc.
• Inventors: See, Jackie R., Summers, David P.
• Primary Examiner(s): Buiz, Michael
• Assistant Examiner(s): Woo, Julian W.
• Application Number:
  US08/797,743
• Time in Patent Office: 1,005 Days
• Field of Search: 606/154, 606/194, 606/195, 606/198, 623/1, 424/450
• US Class Current: 606/194
• CPC Class Codes: A61F 2/0077 Special surfaces of prostheses, e.g. for improving ingrowth A61F2/30767 takes precedence
• CPC Class Codes: A61F 2/07 Stent-grafts
• CPC Class Codes: A61F 2/885 comprising a coil including a plurality of spiral or helical sections with alternate directions around a central axis
• CPC Class Codes: A61F 2002/072 Encapsulated stents, e.g. wire or whole stent embedded in lining
• CPC Class Codes: A61L 2300/22 Lipids, fatty acids, e.g. prostaglandins, oils, fats, waxes
• 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 2300/606 Coatings
• CPC Class Codes: A61L 2300/622 Microcapsules
• CPC Class Codes: A61L 2300/626 Liposomes, micelles, vesicles
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: A61L 31/146 Porous materials, e.g. foams or sponges
• CPC Class Codes: A61L 31/148 Materials at least partially resorbable by the body
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: A61M 2025/0057 Catheters delivering medicament other than through a conventional lumen, e.g. porous walls or hydrogel coatings
• CPC Class Codes: C08L 39/06 Homopolymers or copolymers of N-vinyl-pyrrolidones
• CPC Class Codes: C08L 67/04 Polyesters derived from hydroxycarboxylic acids, e.g. lactones C08L67/06 takes precedence
• CPC Class Codes: C08L 71/02 Polyalkylene oxides

Abstract

A stent or vascular graft for supporting a blood vessel or organ lumen is coated with a biodegradable, resorbable and hemocompatible surface substrate. Biologically active microspheres which controllably release the biologically active agent into the vessel wall or organ to inhibit restenosis of the stent is embedded in the stent substrate. The biologically active microspheres include encapsulated PGE1 in a water soluble polyethylene glycol mix, which over a period of time dissolves and releases the PGE1 into the vessel wall or organ.

Claims

1. A stent for supporting a blood vessel, comprising:

(a) a stent body;

(b) a biodegradable, porous stent substrate swelled in 40% trifluoacetic acid with polyethylene oxide applied on said stent body, wherein the pores of said stent substrate are opened upon swelling said stent substrate; and

(c) a polymer mixture coating said stent substrate, said polymer mixture including biologically active microspheres, and wherein said polymer mixture fills and collapes the pores of said stent substrate.

2. The stent of claim 1 wherein said substrate comprises one or more layers of a resorbable PLLA/PLC mixture encapsulating said stent body.

3. The stent of claim 2 wherein said water soluble polymer mixture comprises a slurry of polyethylene glycol (PEG) and liposomes carrying a biologically active agent.

4. The stent of claim 1 wherein said stent substrate comprises a Poly-L-lactic acid/Polycaprolactone mixture encapsulating said stent body, and wherein said polymer mixture comprises a Polyethylene glycol/lyophilized liposome surface coating on said stent body, and wherein the liposomes in said surface coating range in average diameter from about 100 nm to 200 nm.

5. The stent of claim 2 wherein said stent substrate and said polymer mixture are water soluble and resorbable, providing a continuous and gradual release of prostaglandin encapsulated in said biologically active microspheres.

6. The stent of claim 1 wherein the pores of said stent substrate define an irregular pore surface for releaseably retaining said biologically active microspheres, and wherein said microspheres contain prostaglandin E1 encapsulated in said microspheres.

7. The stent of claim 6 wherein the pores of said stent substrate have a mean pore size of 150 nm to 200 nm long axis and 50 nm to 75 nm short axis.

8. The stent of claim 7 wherein said microspheres release prostaglandin E1 at a controlled rate for up to six months.

9. The stent of claim 1 wherein said stent substrate has a porosity of 18% to 45%.

10. A method of modifying cellular response in a blood vessel or organ to a disease, injury or foreign body, comprising the steps of:

a) forming a water soluble and resorbable hemocompatible stent coating;

b) swelling said stent coating in 40% trifluoacetic acid with polyethylene oxide to open the pores of said stent coating;

c) embedding microspheres having a biologically active agent encapsuled in said microspheres in said stent coating;

d) applying said stent coating on a stent body;

e) positioning said stent body in the blood vessel or organ; and

f) controllably releasing said biologically active agent into the blood vessel wall or target organ.