Treatment Of Diabetic Patients With A Drug Eluting Stent And Adjunctive Therapy

• US 20130224255A1
• Filed: 02/23/2012
• Published: 08/29/2013
• Est. Priority Date: 02/23/2012
• Status: Active Grant

• Current Assignee: Abbott Cardiovascular Systems Incorporated (Abbott Laboratories)
• Original Assignee: Abbott Cardiovascular Systems Incorporated (Abbott Laboratories)
• Inventors: Hossainy, Syed F.A., Consigny, Paul M.
• Granted Patent: US 9,220,759 B2
• Time in Patent Office: Days
• US Class Current: 424/400
• 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 2250/0067 Means for introducing or releasing pharmaceutical products into the body
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/426 1,3-Thiazoles
• 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 31/4365 the heterocyclic ring system having sulfur as a ring hetero atom, e.g. ticlopidine
• CPC Class Codes: A61K 31/45 having oxo groups directly attached to the heterocyclic ring, e.g. cycloheximide
• CPC Class Codes: A61K 31/4709 Non-condensed quinolines and containing further heterocyclic rings
• CPC Class Codes: A61K 31/506 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61K 31/553 having at least one nitrogen and one oxygen as ring hetero atoms, e.g. loxapine, staurosporine
• CPC Class Codes: A61K 31/565 not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 31/65 Tetracyclines
• CPC Class Codes: A61K 35/58 Reptiles antigens from snakes A61K39/38
• CPC Class Codes: A61K 38/28 Insulins
• CPC Class Codes: A61K 38/58 from leeches, e.g. hirudin, eglin
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid

Abstract

Embodiments of the present invention include methods for the treatment, prevention, or amelioration of vascular disease in diabetic patients. The methods include both implantation of a stent including a first drug. Some embodiments include additional therapy, such as the co-administration of another drug. Some embodiments involve different stent selection for a diabetic patient compared to a non-diabetic patient.

Claims

1. A method of treating, preventing, or ameliorating a vascular disease in a diabetic patient, the method comprising:

implanting a stent comprising a first drug in a vascular region of a diabetic patient; and

administering a second drug to the diabetic patient;

wherein the first drug is an anti-inflammatory, an antiproliferative, an antineoplastic, an antimitotic, an antiplatelet, an anticoagulant, an antifibrin, an antithrombin, an antibiotic, an anti-allergic, an antioxidant substance, or any combination thereof; and

wherein the second drug reduces inflammation, reduces the amount, the activity, or both the amount and the activity of tumor necrosis factor alpha, improves the responsiveness of the artery to insulin, reduces platelet activation, reduces fluctuation in hemoglobin AlC, reduces tissue factor activity, reduces thrombin activity, or any combination thereof.

2. The method of claim 1, wherein the second drug is administered orally or transdermally over a time period which begins at least at the time of the implantation of the stent and ends at least 1 month after the implantation of the stent.

3. The method of claim 2, wherein the second drug is administered orally or transdermally over a time period which begins at least 7 days prior to the implantation of the stent and ends at least 1 month after the implantation of the stent.

4. The method of claim 2, wherein the time period over which the second drug is administered ends at least 6 months after the implantation of the stent.

5. The method of claim 2, wherein the time period over which the second drug is administered ends at 6 months after the implantation of the stent or at about 6 months after the implantation of the stent.

6. The method of claim 1, wherein the second drug is administered by subcutaneous or intravenous injection over a time period beginning at least 2 hours prior to the implantation of the stent and continuing to at least 2 hours post-implantation of the stent.

7. The method of claim 1, wherein the second drug is administered intra-arterially via an introducer, a catheter, or both an introducer and a catheter.

8. The method of claim 2, wherein the second drug is administered orally and is an anti-microbial.

9. The method of claim 8, wherein the second drug is doxycycline.

10. The method of claim 2, wherein the second drug is a glitazone.

11. The method of claim 2, wherein the second drug is administered orally, and the second drug is cilostazol, prasugrel, tigacrelor, or a combination thereof.

12. The method of claim 2, wherein the second drug is administered orally, and the second drug is an anti-IL-6.

13. The method of claim 2, wherein the second drug is administered transdermally, and is an anti-TNF biologic.

14. The method of claim 6, wherein the second drug is administered intravenously and is an anti-microbial.

15. The method of claim 14, wherein the second drug is doxycycline.

16. The method of claim 2, wherein the second drug is administered at a dose such that the plasma concentration is lower than the therapeutic index for normal use.

17. The method of claim 2, wherein the second drug is administered in one or more cycles, each cycle comprising administration at a first dose such that the plasma concentration is within therapeutic index for normal use and then a subsequent administration at a second lower dose such that the plasma concentration is below the therapeutic index for normal use.

18. The method of claim 6, wherein the second drug is administered at a dose such that the plasma concentration is lower than the therapeutic index for normal use.

19. The method of claim 6, wherein the second drug is administered in one or more cycles, each cycle comprising administration at a first dose such that the plasma concentration is within therapeutic range for normal use and then subsequent administration at a second lower dose such that the plasma concentration is below the therapeutic index for normal use.

20. The method of claim 1, wherein the second drug is adalimumab and is administered subcutaneously.

21. The method of claim 20, wherein the subcutaneous administration occurs at 2 hours or at about 2 hours prior to the stent deployment, during stent deployment, and at 2 hours or at about 2 hours after stent deployment.

22. The method of claim 9, wherein the first drug is selected from the group consisting of rapamycin (sirolimus), Biolimus A9, deforolimus, AP23572, tacrolimus, temsirolimus, pimecrolimus, novolimus, zotarolimus (ABT-578), 40-O-(2-hydroxy)ethyl-rapamycin (everolimus), 40-O-(3-hydroxypropyl)rapamycin 40-O-[2-(2-hydroxy)ethoxy]ethyl-rapamycin, 40-O-tetrazolylrapamycin, 40-epi-(N1-tetrazolyl)-rapamycin, dexamethasone, myolimus actinomycins, taxol, paclitaxel, docetaxel, estradiol, 17-beta-estradiol, nitric oxide donors, super oxide dismutases, super oxide dismutases mimics, 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl (4-amino-TEMPO), dexamethasone, γ

-hiridun, clobetasol, pimecrolimus, imatinib mesylate, midostaurin, and combinations thereof.

23. The method of claim 10, wherein the first drug is selected from the group consisting of rapamycin (sirolimus), Biolimus A9, deforolimus, AP23572, tacrolimus, temsirolimus, pimecrolimus, novolimus, zotarolimus (ABT-578), 40-O-(2-hydroxy)ethyl-rapamycin (everolimus), 40-O-(3-hydroxypropyl)rapamycin 40-O-[2-(2-hydroxy)ethoxy]ethyl-rapamycin, 40-O-tetrazolylrapamycin, 40-epi-(N1-tetrazolyl)-rapamycin, dexamethasone, myolimus actinomycins, taxol, paclitaxel, docetaxel, estradiol, 17-beta-estradiol, nitric oxide donors, super oxide dismutases, super oxide dismutases mimics, 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl (4-amino-TEMPO), dexamethasone, γ

-hiridun, clobetasol, pimecrolimus, imatinib mesylate, midostaurin, and combinations thereof.

24. The method of claim 16, wherein the first drug is selected from the group consisting of rapamycin (sirolimus), Biolimus A9, deforolimus, AP23572, tacrolimus, temsirolimus, pimecrolimus, novolimus, zotarolimus (ABT-578), 40-O-(2-hydroxy)ethyl-rapamycin (everolimus), 40-O-(3-hydroxypropyl)rapamycin 40-O-[2-(2-hydroxy)ethoxy]ethyl-rapamycin, 40-O-tetrazolylrapamycin, 40-epi-(N1-tetrazolyl)-rapamycin, dexamethasone, myolimus actinomycins, taxol, paclitaxel, docetaxel, estradiol, 17-beta-estradiol, nitric oxide donors, super oxide dismutases, super oxide dismutases mimics, 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl (4-amino-TEMPO), dexamethasone, γ

-hiridun, clobetasol, pimecrolimus, imatinib mesylate, midostaurin, and combinations thereof.

25. The method of claim 17, wherein the first drug is selected from the group consisting of rapamycin (sirolimus), Biolimus A9, deforolimus, AP23572, tacrolimus, temsirolimus, pimecrolimus, novolimus, zotarolimus (ABT-578), 40-O-(2-hydroxy)ethyl-rapamycin (everolimus), 40-O-(3-hydroxypropyl)rapamycin 40-O-[2-(2-hydroxy)ethoxy]ethyl-rapamycin, 40-O-tetrazolylrapamycin, 40-epi-(N1-tetrazolyl)-rapamycin, dexamethasone, myolimus actinomycins, taxol, paclitaxel, docetaxel, estradiol, 17-beta-estradiol, nitric oxide donors, super oxide dismutases, super oxide dismutases mimics, 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl (4-amino-TEMPO), dexamethasone, γ

-hiridun, clobetasol, pimecrolimus, imatinib mesylate, midostaurin, and combinations thereof.

26. The method of claim 18, wherein the first drug is selected from the group consisting of rapamycin (sirolimus), Biolimus A9, deforolimus, AP23572, tacrolimus, temsirolimus, pimecrolimus, novolimus, zotarolimus (ABT-578), 40-O-(2-hydroxy)ethyl-rapamycin (everolimus), 40-O-(3-hydroxypropyl)rapamycin 40-O-[2-(2-hydroxy)ethoxy]ethyl-rapamycin, 40-O-tetrazolylrapamycin, 40-epi-(N1-tetrazolyl)-rapamycin, dexamethasone, myolimus actinomycins, taxol, paclitaxel, docetaxel, estradiol, 17-beta-estradiol, nitric oxide donors, super oxide dismutases, super oxide dismutases mimics, 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl (4-amino-TEMPO), dexamethasone, γ

-hiridun, clobetasol, pimecrolimus, imatinib mesylate, midostaurin, and combinations thereof.

27. The method of claim 19, wherein the first drug is selected from the group consisting of rapamycin (sirolimus), Biolimus A9, deforolimus, AP23572, tacrolimus, temsirolimus, pimecrolimus, novolimus, zotarolimus (ABT-578), 40-O-(2-hydroxy)ethyl-rapamycin (everolimus), 40-O-(3-hydroxypropyl)rapamycin 40-O-[2-(2-hydroxy)ethoxy]ethyl-rapamycin, 40-O-tetrazolylrapamycin, 40-epi-(N1-tetrazolyl)-rapamycin, dexamethasone, myolimus actinomycins, taxol, paclitaxel, docetaxel, estradiol, 17-beta-estradiol, nitric oxide donors, super oxide dismutases, super oxide dismutases mimics, 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl (4-amino-TEMPO), dexamethasone, γ

-hiridun, clobetasol, pimecrolimus, imatinib mesylate, midostaurin, and combinations thereof.

28. A method of treating, preventing, or ameliorating a vascular disease in a diabetic patient, the method comprising:

implanting a stent comprising a first drug in a vascular region of a diabetic patient; and

administering a food or food supplement of complex carbohydrates to the diabetic patient for a time period encompassing the time of stent implantation.

29. A method of treating, preventing, or ameliorating a vascular disease in a diabetic patient, the method comprising:

selecting a stent with higher surface area at the edges than in the middle of the stent, selecting a stent of a length that is 5 mm longer at each end than the length that would be selected for a non-diabetic patient, or selecting a stent with higher surface area at the edges than in the middle of the stent that is of a length that is 5 mm longer at each end than the length that would be selected for a non-diabetic patient; and

implanting a stent comprising a first drug in a vascular region of a diabetic patient.