Delivery of therapeutic capable agents

• US 20030139801A1
• Filed: 07/25/2002
• Published: 07/24/2003
• Est. Priority Date: 12/22/2000
• Status: Active Grant

• Current Assignee: Avantec Vascular Corporation
• Original Assignee: Avantec Vascular Corporation
• Inventors: Yan, John, Sirhan, Motasim
• Granted Patent: US 7,083,642 B2
• Time in Patent Office: Days
• US Class Current: 623/1.15
• 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 2/95 Instruments specially adapted for placement or removal of stents or stent-grafts
• CPC Class Codes: A61F 2002/91533 characterised by the phase between adjacent bands
• CPC Class Codes: A61F 2002/91558 connected peak to peak
• CPC Class Codes: A61F 2230/0054 V-shaped
• CPC Class Codes: A61F 2250/0067 Means for introducing or releasing pharmaceutical products into the body
• CPC Class Codes: A61F 2250/0071 breakable or frangible
• 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 2300/602 Type of release, e.g. controlled, sustained, slow
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence

Abstract

The present invention provides improved stents and other prostheses for delivering substances to vascular and other luminal and intracorporeal environments. In particular, the present invention provides for therapeutic capable agent eluting stents with minimized undesirable loss of the therapeutic capable agent during expansion of the stent.

Claims

1. A device for intracorporeal use within a patient'"'"'s body, comprising:

a structure; and

at least one source of at least one therapeutic capable agent associated with the structure and being configured to minimize undesirable loss of the therapeutic capable agent due to expansion of the structure.

2. A device as in claim 1, wherein the undesirable loss is manifested as flaking off or dislodging of the therapeutic capable agent from the device.

3. A device as in claim 1, wherein the undesirable loss occurs as a result of the device undergoing stress or strain during expansion of the device within the patient'"'"'s body.

4. A device as in claim 1, 2, or 3, wherein the therapeutic capable agent is selected from the group consisting of immunosuppressants, anti-inflammatories, anti-proliferatives, anti-migratory agents, anti-fibrotic agents, proapoptotics, vasodilators, calcium channel blockers, anti-neoplastics, anti-cancer agents, antibodies, anti-thrombotic agents, anti-platelet agents, IIb/IIIa agents, antiviral agents, mTOR (mammalian target of rapamycin) inhibitors, non-immunosuppressant agents, and combinations thereof.

5. A device as in claim 1, 2, or 3, wherein the therapeutic capable agent is selected from the group consisting of mycophenolic acid, mycophenolic acid derivatives (e.g., 2-methoxymethyl derivative and 2-methyl derivative), VX-148, VX-944, mycophenolate mofetil, mizoribine, methylprednisolone, dexamethasone, CERTICAN™

(e.g., everolimus, RAD), rapamycin, ABT-773 (Abbot Labs), ABT-797 (Abbot Labs), TRIPTOLIDE™

, METHOTREXATE™

, phenylalkylamines (e.g., verapamil), benzothiazepines (e.g., diltiazem), 1,4-dihydropyridines (e.g., benidipine, nifedipine, nicarrdipine, isradipine, felodipine, amlodipine, nilvadipine, nisoldipine, manidipine, nitrendipine, barnidipine (HYPOCA™

)), ASCOMYCIN™

, WORTMANNIN™

, LY294002, CAMPTOTHECIN™

, flavopiridol, isoquinoline, HA-1077 (l-(5-isoquinolinesulfonyl)-homopiperazine hydrochloride), TAS-301 (3-bis(4-methoxyphenyl)methylene-2-indolinone), TOPOTECAN™

, hydroxyurea, TACROLIMUS™

(FK

     506), cyclophosphamide, cyclosporine, daclizumab, azathioprine, prednisone, diferuloymethane, diferuloylmethane, diferulylmethane, GEMCITABINE™

, cilostazol (PLETAL™

), tranilast, enalapril, quercetin, suramin, estradiol, cycloheximide, tiazofurin, zafurin, AP23573, rapamycin derivatives, non-immunosuppressive analogues of rapamycin (e.g., rapalog, AP21967, derivatives of rapalog), CCI-779 (an analogue of rapamycin available from Wyeth), sodium mycophernolic acid, benidipine hydrochloride, sirolimus, rapamine, metabolites, derivatives and combinations thereof.

6. A device as in claim 1, 2, or 3, wherein the therapeutic capable agent is selected from the group consisting of mycophenolic acid, mycophenolate mofetil, rapamycin, CERTICAN™

(everolimus, RAD), TRIPTOLIDE™

, benidipine, TACROLIMUS™

(FK

     506), cilostazol (PLETAL™

), metabolites, derivatives and combinations thereof.

7. A device for intracorporeal use, the device comprising:

a structure; and

at least one source of at least one therapeutic capable agent associated with the structure and having a textured surface.

8. A device as in claim 7, wherein the therapeutic capable agent surface has peaks and valleys with a distance between the peaks ranging from about 0.1 μ

m to about 50 μ

m.

9. A device as in claim 7, wherein the therapeutic capable agent surface has peaks and valleys with a distance between peaks ranging from about 1 μ

m to about 35 μ

m.

10. A device as in claim 7, wherein the therapeutic capable agent surface has peaks and valleys with a distance between the peaks ranging from about 5 μ

m to about 20 μ

m.

11. A device as in claim 8, 9, or 10, wherein the distance between the peaks is a mean distance.

12. A device as in claim 7, wherein the therapeutic capable agent surface has peaks and valleys with a peak height ranging from about 0.01 μ

m to about 10 μ

m.

13. A device as in claim 7, wherein the therapeutic capable agent surface has peaks and valleys with a peak height ranging from about 0.05 μ

m to about 1.5 μ

m.

14. A device as in claim 7, wherein the therapeutic capable agent surface has peaks and valleys with a peak height ranging from about 0.1 μ

m to about 1 μ

m.

15. A device as in claim, 12, 13, or 14, wherein the peak height is an average peak height.

16. A device as in claim 7, wherein the therapeutic capable agent forms a layer ranging from about 0.1 μ

m to about 20 μ

m.

17. A device as in claim 7, wherein the therapeutic capable agent forms a layer having a thickness ranging from about 0.5 μ

m to about 7.5 μ

m.

18. A device as in claim 7, wherein the therapeutic capable agent forms a layer having a thickness ranging from about 1.0 μ

m to about 5 μ

m

19. A device as in claim 16, 17, or 18, wherein the layer thickness is an average thickness.

20. A device as in claim 7, wherein the textured therapeutic capable agent surface forms the outer most layer of the device.

21. A device as in claim 7, wherein the therapeutic capable agent is selected from the group consisting of immunosuppressants, anti-inflammatories, anti-proliferatives, anti-migratory agents, anti-fibrotic agents, proapoptotics, vasodilators, calcium channel blockers, anti-neoplastics, anti-cancer agents, antibodies, anti-thrombotic agents, anti-platelet agents, IIb/IIIa agents, antiviral agents, mTOR (mammalian target of rapamycin) inhibitors, non-immunosuppressant agents, and combinations thereof.

22. A device as in claim 7, wherein the therapeutic capable agent is selected from the group consisting of mycophenolic acid, mycophenolic acid derivatives (e.g., 2-methoxymethyl derivative and 2-methyl derivative), VX-148, VX-944, mycophenolate mofetil, mizoribine, methylprednisolone, dexamethasone, CERTICAN™

(e.g., everolimus, RAD), rapamycin, ABT-773 (Abbot Labs), ABT-797 (Abbot Labs), TRIPTOLIDE™

, METHOTREXATE™

, phenylalkylamines (e.g., verapamil), benzothiazepines (e.g., diltiazem), 1,4-dihydropyridines (e.g., benidipine, nifedipine, nicarrdipine, isradipine, felodipine, amlodipine, nilvadipine, nisoldipine, manidipine, nitrendipine, barnidipine (HYPOCA™

)), ASCOMYCIN™

, WORTMANNIN™

, LY294002, CAMPTOTHECIN™

, flavopiridol, isoquinoline, HA-1077 (1-(5-isoquinolinesulfonyl)-homopiperazine hydrochloride), TAS-301 (3-bis(4-methoxyphenyl)methylene-2-indolinone), TOPOTECAN™

, hydroxyurea, TACROLIMUS™

(FK

     506), cyclophosphamide, cyclosporine, daclizumab, azathioprine, prednisone, diferuloymethane, diferuloylmethane, diferulylmethane, GEMCITABINE™

, cilostazol (PLETAL™

), tranilast, enalapril, quercetin, suramin, estradiol, cycloheximide, tiazofurin, zafurin, AP23573, rapamycin derivatives, non-immunosuppressive analogues of rapamycin (e.g., rapalog, AP21967, derivatives of rapalog), CCI-779 (an analogue of rapamycin available from Wyeth), sodium mycophernolic acid, benidipine hydrochloride, sirolimus, rapamine, metabolites, derivatives and combinations thereof.

23. A device as in claim 7, wherein the therapeutic capable agent is selected from the group consisting of mycophenolic acid, mycophenolate mofetil, rapamycin, CERTICAN™

(everolimus, RAD), TRIPTOLIDE™

, benidipine, TACROLIMUS™

(FK

     506), cilostazol (PLETAL™

), metabolites, derivatives and combinations thereof.

24. A device for intracorporeal use, the device comprising:

a radially expansible implantable scaffold having a plurality of regions exhibiting different mechanical profiles during expansion of the scaffold and including relatively lower and relatively higher mechanical profiles; and

a source of at least one therapeutic capable agent having a plurality of segments and disposed adjacent at least a portion of the scaffold.

25. A device as in claim 24, wherein the therapeutic capable agent segments are disposed adjacent the relatively lower mechanical profile regions.

26. A device as in claim 24, wherein the segments are disposed adjacent only the regions that do not undergo substantial bending, flexing, stretching, or compressing upon the expansion of the scaffold.

27. A device as in claim 24, wherein the therapeutic capable agent segments are disposed adjacent only the regions that do not undergo more than about 5% of bending, flexing, stretching, or compressing upon the expansion of the scaffold.

28. A device as in claim 24, wherein the therapeutic capable agent segments are disposed along either or both abluminal and tissue facing surfaces of the scaffold.

29. A device as in claim 24, wherein the therapeutic capable agent segments are disposed along an outer surface of the scaffold and away from sides or edges of the scaffold.

30. A method for treatment of a patient, the method comprising:

providing a vascular prosthesis comprising a structure and at least one source of at least one therapeutic capable agent associated with the structure;

implanting the vascular prosthesis within the patient'"'"'s vasculature including a susceptible tissue site; and

releasing the at least one therapeutic capable agent, wherein the source is configured to minimize undesirable loss of the therapeutic capable agent.

31. A method for treatment of a patient, the method comprising:

providing a vascular prosthesis comprising a structure and at least one source of at least one therapeutic capable agent associated with the structure and having a textured surface;

implanting the vascular prosthesis within the patient'"'"'s vasculature including a susceptible tissue site; and

releasing the at least one therapeutic capable agent.

32. A method for treatment of a patient, the method comprising:

providing a vascular prosthesis comprising a structure having a plurality of regions exhibiting relatively lower and relatively higher mechanical profiles and at least one source of at least one therapeutic capable agent disposed adjacent the relatively lower mechanical profile regions;

implanting the vascular prosthesis within the patient'"'"'s vasculature including a susceptible tissue site; and

releasing the at least one therapeutic capable agent.