Inherently radiopaque bioresorbable polymers for multiple uses

• US 20060036316A1
• Filed: 08/10/2005
• Published: 02/16/2006
• Est. Priority Date: 08/13/2004
• Status: Active Grant

• Current Assignee: REVA Medical LLC
• Original Assignee: REVA Medical Inc.
• Inventors: Zeltinger, Joan, Brandom, Donald K.
• Granted Patent: US 7,473,417 B2
• Time in Patent Office: Days
• US Class Current: 623/1.490
• 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 2/915 with bands having a meander structure, adjacent bands being connected to each other
• CPC Class Codes: A61F 2002/91533 characterised by the phase between adjacent bands
• CPC Class Codes: A61F 2002/91591 Locking connectors, e.g. using male-female connections
• CPC Class Codes: A61F 2210/0004 bioabsorbable
• CPC Class Codes: A61K 49/0442 Polymeric X-ray contrast-enhancing agent comprising a halogenated group
• CPC Class Codes: A61L 31/18 Materials at least partially X-ray or laser opaque
• CPC Class Codes: A61P 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: B33Y 70/00 Materials specially adapted for additive manufacturing
• CPC Class Codes: B33Y 80/00 Products made by additive manufacturing
• CPC Class Codes: C08G 64/08 containing atoms other than carbon, hydrogen or oxygen
• CPC Class Codes: C08G 64/18 Block or graft polymers
• CPC Class Codes: C08G 65/4006 (I) or (II) containing elements other than carbon, oxygen, hydrogen or halogen as leaving group (X)

Abstract

Preferred embodiments of the present invention relate to polymeric medical devices, such as stents. More particularly, the compositions disclosed herein comprise halogen-containing phenol moeities, that may be used for medical devices and other uses whereby bioresorbable and radiopaque and physicomechanical properties are desired.

Claims

1. An inherently radiopaque, biocompatible, bioresorbable polymer, wherein said polymer comprises one or more recurring units of the Formula (I):

wherein;

X¹ and X² are each independently selected from the group consisting of Br and I;

y1 and y2 are each independently zero or an integer in the range of 1 to 4, with the proviso that the sum of y1 and y2 is at least 1;

R¹ is

R¹³ and R¹⁴ are each independently selected from the group consisting of —

CH═

CH—

, —

(CH₂)_c—

, —

(CHJ¹)—

, —

CHJ²—

CHJ³—

, —

CH═

CH—

(CHJ¹)—

, and —

(CH₂)_c—

(CHJ¹)—

;

c is zero or an integer in the range of 1 to 8;

J¹, J² and J³ are each independently selected from the group consisting of H, Br, I, —

NH-Q² and C(=Z⁸)-OQ³;

Q¹, Q² and Q³ are each independently H or a non-crystallizable group comprising from about 1 to about 30 carbons;

Z⁷ and Z⁸ are each independetly O or S;

A¹ is selected from the group consisting of

R⁵ is selected from the group consisting of H, C₁-C₃₀ alkyl, and C₁-C₃₀ heteroalkyl.

2. A medical device comprising the polymer of claim 1.

3. The medical device of claim 2, wherein said medical device is configured for placement in a region selected from vascular, musculoskeletal/orthopedic, nervous, respiratory, reproductive, urinary, digestive, endocrine, hematopoietic, or integumentary system.

4. The medical device of claim 2, wherein said medical device is configured for use in vivo.

5. The medical device of claim 2, wherein said medical device is configured for use ex vivo.

6. The medical device of claim 5, wherein said medical device is configured for use in vitro.

7. The medical device of claim 2, wherein said medical device comprises a stent.

8. The medical device of claim 7, wherein said stent further comprises a configuration selected from the group consisting of a sheet stent, a braided stent, a self-expanding stent, a wire stent, a deformable stent, and a slide-and-lock stent.

9. The medical device of claim 7, wherein said stent comprises at least two substantially non-deforming elements arranged to form a tubular member, the non-deforming elements being slidably interconnected for allowing the tubular member to expand from a collapsed diameter to an expanded diameter.

10. The medical device of claim 7, wherein said stent further comprises a tubular member comprising a series of slideably-engaged radial elements and a locking mechanism adapted to permit one-way sliding of the radial elements, such that said tubular member is configured to expand from a first collapsed diameter to a second expanded diameter with minimum recoil.

11. The medical device of claim 2, further comprising an effective amount of a therapeutic agent.

12. The medical device of claim 11, wherein said therapeutic agent is selected from the group consisting of antiproliferative agent, anti-inflammatory agent, anti-matrix metalloproteinase agent, lipid lowering agent, cholesterol modifying agent, anti-thrombotic agent, and antiplatelet agent.

13. The medical device of claim 11, wherein said effective amount is sufficient to provide an effect selected from the group consisting of inhibition of restenosis, inhibition of thrombosis, inhibition of plaque formation, inhibition of plaque rupture, inhibition of inflammation, lowering of cholesterol, and promote healing.

14. The medical device of claim 2, wherein X¹ and X² are iodine.

15. The medical device of claim 2 further comprising a non-halogenated coating.

16. The medical device of claim 2, wherein said polymer forms a coating on at least a portion of said medical device.

17. A system for treating a site within a vessel, comprising the stent of claim 7 and a catheter having a deployment means, wherein said catheter is adapted to deliver the stent to said site and said deployment means is adapted to deploy the stent.

18. A method for re-treatment of a body lumen, comprising:

deploying a first stent along a region within a blood vessel, wherein said first stent is the stent of claim 7, and wherein said first stent resides for a period of time; and

deploying at a later time a second stent, along the approximate same region within the blood vessel, such that the blood vessel is re-treated.

19. The polymer of claim 1, further comprising one or more recurring units of the Formula (II):

wherein;

B is —

O—

(CHR⁶)_p—

O)_q—

;

R⁶ is H or C₁ to C₃ alkyl;

p and q are each individually an integer in the range of about 1 to about 100;

A² is selected from the group consisting of

R⁷ is H or a C₁ to C₃₀ hydrocarbon; and

R¹¹ is selected from the group consisting of C₁-C₃₀ alkyl, C₁-C₃₀ heteroalkyl, C₅-C₃₀ aryl, C₆-C₃₀ alkylaryl, and C₂-C₃₀ heteroaryl.

20. A medical device comprising the polymer of claim 19.

21. The polymer of claim 19, further comprising one or more recurring units of the Formula (Ia):

wherein;

X³ and X⁴ are each independently selected from the group consisting of Br and I;

y3 and y4 are each independently zero or an integer in the range of 1 to 4;

R² is selected from the group consisting of;

R⁸ and R⁹ are each independently H or a non-crystallizable C₁ to C₃₀ hydrocarbon;

Z⁴, Z⁵ and Z⁶ are each independently O or S;

a and b are each independently an integer in the range of 1 to 8;

A³ is selected from the group consisting of

R¹⁰ is selected from the group consisting of H, C₁-C₃₀ alkyl, and C₁-C₃₀ heteroalkyl; and

R¹² is selected from the group consisting of C₁-C₃₀ alkyl, C₁-C₃₀ heteroalkyl, C₅-C₃₀ aryl, C₆-C₃₀ alkylaryl, and C₂-C₃₀ heteroaryl.

22. A medical device comprising the polymer of claim 21.

23. The polymer of claim 1, wherein R¹ is:

wherein R³ is H or a non-crystallizable C₁ to C₂₉ hydrocarbon;

Z¹ and Z² are each independently O or S; and

m is an integer in the range of 1 to 8.

24. A medical device comprising the polymer of claim 23.

25. The polymer of claim 1, wherein R¹ is:

wherein R³ is H or a non-crystallizable C₁ to C₂₉ hydrocarbon;

Z¹ and Z² are each independently O or S; and

j and m are each independently an integer in the range of 1 to 8.

26. A medical device comprising the polymer of claim 25.

27. The polymer of claim 1, wherein R¹ is:

wherein R³ and R⁴ are each independently H or a non-crystallizable C₁ to C₂₉ hydrocarbon;

Z¹, Z² and Z³ are each independently O or S; and

j and m are each independently an integer in the range of 1 to 8.

28. A medical device comprising the polymer of claim 27.

29. The medical device of claim 2, further comprising an effective amount of a radiopacifying agent.

30. The medical device of claim 2, further comprising an effective amount of a magnetic resonance enhancing agent.