Expandable polymeric stent with memory and delivery apparatus and method

• US 6,248,129 B1
• Filed: 10/23/1998
• Issued: 06/19/2001
• Est. Priority Date: 09/14/1990
• Status: Expired due to Fees

• Current Assignee: Boston Scientific Scimed (Boston Scientific Corporation)
• Original Assignee: Quanam Medical Corp (Boston Scientific Corporation)
• Inventors: Froix, Michael
• Primary Examiner(s): Willse, David H.
• Assistant Examiner(s): GHERBI, SUZETTE JAIME J
• Application Number:
  US09/177,917
• Time in Patent Office: 970 Days
• Field of Search: 623/1, 623/12, 623/1.39, 623/1.42, 623/1.4, 623/1.45, 623/1.49
• US Class Current: 623/1.42
• CPC Class Codes: A61F 2/82 Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents stent-grafts for tubular structures of the body other than blood vessels A61F2/04; stent-grafts for blood vessels A61F2/07; instruments specially adapted for placement or removal of stents or stent-grafts A61F2/95; for closing wounds, or holding wounds closed A61B17/04 - A61B17/115; dilators A61M29/00
• CPC Class Codes: A61F 2/88 the wire-like elements formed as helical or spiral coils forming a net-like or mesh-like structure A61F2/90
• CPC Class Codes: A61F 2/90 characterised by a net-like or mesh-like structure
• CPC Class Codes: A61F 2/94 Stents retaining their form, i.e. not being deformable, after placement in the predetermined place
• CPC Class Codes: A61F 2/958 Inflatable balloons for placing stents or stent-grafts
• CPC Class Codes: A61F 2210/0004 bioabsorbable
• CPC Class Codes: A61F 2210/0042 using a fluid, e.g. circulating
• CPC Class Codes: A61F 2210/0047 heated by light
• CPC Class Codes: A61F 2250/0067 Means for introducing or releasing pharmaceutical products into the body
• CPC Class Codes: A61L 2300/42 Anti-thrombotic agents, anticoagulants, anti-platelet agents
• CPC Class Codes: A61L 2300/602 Type of release, e.g. controlled, sustained, slow
• CPC Class Codes: A61L 2300/622 Microcapsules
• CPC Class Codes: A61L 31/041 Mixtures of macromolecular compounds
• CPC Class Codes: A61L 31/146 Porous materials, e.g. foams or sponges
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: C08L 33/06 of esters containing only carbon, hydrogen and oxygen, which oxygen atoms are present only as part of the carboxyl radical

Abstract

A stent for use in a lumen defined by a wall of a vessel of a patient having a body. The vessel is comprised of a hollow substantially cylindrical member formed of a biocompatible composition. The composition incorporates at least one medical agent in a weight up to 90% of the total weight of the stent so that at least one medical agent is released from the composition of the stent into the vessel at a controlled rate extending over a period of time after the stent is inserted into the vessel.

Claims

1. A stent for use in a lumen defined by a wall of a vessel of a patient having a body with the vessel therein, comprising a hollow substantially cylindrical member formed of a biocompatible composition, said composition being in the form of a polymer matrix, at least one medical agent in a weight up to 90% of the total weight of said member dispersed uniformly throughout said polymer matrix whereby when said stent is disposed in the lumen said at least one medical agent is released at a controlled release rate from the member into said vessel, it must be dissolved in the polymer matrix and thereafter diffuse through the polymer matrix, said controlled release rate extending over a period of time after said lumen stent is inserted into said and being controlled solely by the rate of diffusion of the medical agent from the stent.

2. A stent as in claim 1 wherein said at least one medical agent has been absorbed by said biocompatible composition.

3. A stent as in claim 1 wherein said polymer matrix has a transition characteristic therein whereby when the transition characteristic is activated the substantially cylindrical member will change its dimensions in all directions and assume a greater diameter than the initial predetermined diameter and come into engagement with the wall of the vessel to form a flow passage in the lumen of the vessel.

4. A stent as in claim 1 wherein said member has an initial built-in elastic predetermined diameter which is less than the diameter of the lumen in the vessel so that the substantially cylindrical member can be inserted into the lumen of the vessel, said polymer matrix of said cylindrical member also having a memory based on a transition provided therein of a diameter greater than the built-in elastic predetermined diameter and at least as great as the diameter of the lumen of the vessel, said polymer matrix being characterized in that it will change its dimensions in all directions and will assume the greater diameter in its memory and move into engagement with the wall of the vessel upon the occurrence of one or more of the following conditions selected from the group consisting of:

(a) adsorption of heat by the plastic material;

(b) adsorption of a liquid by the plastic material; and

(c) a change in the pH in the liquid in which the plastic member is disposed.

5. A stent as in claim 1 wherein said member has an initial built-in elastic predetermined diameter which is less than the diameter of the lumen in the vessel so that the substantially cylindrical member can be inserted into the lumen of the vessel, said member also having a memory based on a thermal transition provided therein of a diameter greater than the initial predetermined diameter and at least as great as the diameter of the lumen of the vessel, said member being characterized in that it will assume the greater diameter and move into engagement with the wall of the vessel upon the absorption of heat by the polymer matrix to activate said thermal transition which is achieved by one of the following selected from the group consisting of (a) a melting point of the main chain;

(b) a melting point of the side chain;

(c) a glass transition temperature;

(d) a liquid crystal transition; and

(e) a local mode molecular transition.

6. A stent as in claim 5 wherein said polymer matrix has a thermal transition which is achieved by one of the following:

(a) a melting point of the main chain;

(b) a melting point of a side chain;

(c) a glass transition temperature;

(d) a liquid crystal transition; and

(e) a local mode molecular transition.

7. A stent as in claim 6 wherein said encapsulating means is selected so that the release extends over a time period from several hours to one year.

8. A stent as in claim 1 wherein said medical agent is an anti-platelet drug dispersed in said matrix in a weight of 1% to 50% of said total weight of said matrix so that 80% of said anti-platelet drug diffuses to said wall of a vessel by nine days and 90% by 12 days.

9. A stent as in claim 1 wherein said medical agent is an anticoagulant dispersed in said matrix in a weight of 1% to 50% of said total weight of said matrix so that 80% of said anticoagulant diffuses to said wall of a vessel by two to four weeks.

10. A stent as in claim 1 wherein said medical agent is an anti-oxidant dispersed in said matrix in a weight of 1% to 50% of said total weight of said matrix so that 60% of said anti-oxidant diffuses to said wall of a vessel by ten days and 90% by six months.

11. A stent as in claim 1 wherein said at least one medical agent is Ticlopidine, said Ticlopidine being dispersed in said matrix in a weight of 1% to 50% of said total weight of said matrix so that 80% of said Ticlopidine diffuses out of said matrix to said wall of a vessel by two days and 90% by eight days after insertion of said stent into said vessel.

12. A stent as in claim 1 wherein said at least one medical agent is Ticlopidine, said Ticlopidine being dispersed in said matrix in a weight sufficient so that 80% of said Ticlopidine diffuses out of said matrix to said wall of a vessel by two days and 90% by eight days after insertion of said stent into said vessel.

13. A stent as in claim 1 wherein said at least one medical agent is Heparin, said Heparin being dispersed in said matrix in a weight of 1% to 50% of the total weight of said matrix and wherein 15% to 50% of said Heparin is encapsulated so that 20% to 40% of said Heparin diffuses out of said matrix to said wall of a vessel by two to four hours, an additional 20% to 40% by one day and the remainder of said Heparin by 20 to 30 days after insertion of said stent into said vessel.

14. A stent as in claim 1 wherein said at least one medical agent is Vitamin E, said Vitamin E being dispersed in said matrix in a weight of 1% to 50% of the total weight of said matrix so that 60% of said Vitamin E diffuses out of said matrix to said wall of a vessel by ten days and 80% to 100% by six months after insertion of said stent into said vessel.

15. A stent as in claim 1 wherein said at least one medical agent is glutathione, said glutathione being dispersed in said matrix in a weight of 1% to 50% of the total weight of said matrix so that 20% to 40% of said glutathione diffuses out of said matrix to said wall of a vessel by one day, 50% to 60% by two days, and 90% to 100% by 14 days after insertion of said stent into said vessel.

16. A stent as in claim 1 wherein said at least one medical agent is Warfarin, said Warfarin being dispersed in said matrix in a weight sufficient so that 5% to 25% of said Warfarin diffuses out of said matrix to said wall of a vessel by 45 minutes, 25% to 30% by two to three hours and 30% to 50% by two to three weeks after insertion of said stent into said vessel.

17. A stent as in claim 1 wherein said at least one medical agent is Dicumarol, said Dicumarol being dispersed in said matrix in a weight sufficient so that 40% to 60% of said Dicumarol diffuses out of said matrix to said wall of a vessel by 30 to 90 minutes, 50% to 70% by one-half to two days and 60% to 100% by two to three weeks after insertion of said stent into said vessel.

18. A stent as in claim 1 wherein said encapsulating means further comprises a biodegradable polymer.

19. A stent as in claim 1 wherein said encapsulating means further comprises a copolymer, said copolymer being formed of the components polylactic and polyglycolic acid in a ratio of polylactic acid to polyglycolic acid ranging from 5 to 95.

20. A stent as in claims 1 wherein said at least one medical agent is selected from the group consisting of

(a) Ticlopidine;

(b) Heparin;

(c) Glutathione;

(d) Anti-sense nucleotide;

(e) Vitamin E

(f) Warfarin

(g) Dicumarol

(h) ReoPro

(i) tissue plasminogen activator

(j) Urokinase

(k) Streptokinase

(l) enzymes.

21. A stent as in claim 1 wherein said entrapment means is selected so that said diffusion extends over a time period from several hours to one year.

22. A stent as in claim 1 wherein said entrapment means further comprises using micro- and macro-porous randomly shaped particles, said particles having an average particle size ranging from 5 microns to 50 microns in diameter and having an average surface area ranging from 20 m²/gram to 700 m²/gram, said particles being made from compounds selected from the group consisting of (a) polyacrylates;

(b) polystyrenes;

(c) methacrylates;

(d) polycarbonate;

(e) nylons;

(f) polyaryletherketones;

(g) polybutadene;

(h) polybutadene copolymers;

(i) polysulfones;

(j) polyethylenes;

(k) aluminum oxide;

(l) diatomaceous earth;

(m) silicas; and

(n) silicates.

23. A stent as in claim 1 wherein said medical agent is an anti-sense nucleotide dispersed in said matrix in a weight of 1% to 50% of said total weight of said matrix so that 30% to 60% diffuses out of said matrix to said wall of a vessel by one day and the remainder within one week.

24. A stent as in claim 13 wherein said Ticlopidine is dispersed in said matrix in a weight of 1% to 50% of said total weight of said matrix, 90% to 100% of said Ticlopidine is encapsulated and said copolymer is formed of said components in a ratio of half-and-half so that 80% of said Ticlopidine diffuses out of said matrix to said vessel by nine days and 90% by 12 days after insertion of said stent into said vessel.

25. A stent as in claim 22 wherein said at least one medical agent is an anti-oxidant, said anti-oxidant being dispersed in said matrix in a weight of 1% to 50% of said total weight of said matrix and 80% to 100% of said anti-oxidant being entrapped so that 40% of said anti-oxidant diffuses out of said matrix to said wall of a vessel by 12 hours and the remainder by four months after insertion of said stent into said vessel.

26. A stent as in claim 22 wherein said at least one medical agent is an anti-sense oligonucleotide, said anti-sense oligonucleotide being dispersed in said matrix in a weight of 1% to 50% of the total weight of said matrix and 80% to 100% of said anti-sense oligonucleotide being entrapped so that 30% to 60% of said anti-sense oligonucleotide diffuses out of said matrix to said wall of a vessel by seven to ten hours and the remainder of said anti-sense oligonucleotide by three to four days after insertion of said stent into said vessel.

27. A stent for use in a lumen defined by a wall of a vessel of a patient having a body with the vessel therein, comprising a hollow substantially cylindrical member formed of a biocompatible composition in the form of a polymer matrix and having an outer surface, said polymer matrix carrying at least one medical agent uniformly dispersed in said polymer matrix and which is at least partially disposed below the surface of said member so that said at least one medical agent is released from the member by being dissolved and then diffusing through the polymer matrix at controlled release rate extending over a period of time after said stent is inserted into the lumen, said member being free of biodegradable material whereby said controlled release is determined solely by the rate diffusion of the medical agent from the stent.

28. A stent as in claim 27 wherein said medical agent is incorporated as a component of a multi-component biocompatible composition for the stent.