Coating formulations for scoring or cutting balloon catheters

Abstract

The present invention is related to scoring or cutting balloon catheters carrying at least on a portion of their surface at least one drug or drug preparation and at least one lipophilic antioxidant at a ratio of 3-100% by weight of the at least one lipophilic antioxidant in relation to 100% by weight of the drug, wherein a combination of the at least one drug being a limus drug and the at least one lipophilic antioxidant being butylated hydroxytoluene is excluded.

Claims

1. A balloon catheter for angioplasty or coronary angioplasty comprising: a shaft having a proximal portion and a distal portion; an inflatable balloon coupled to the distal portion of the shaft; a nonimplantable scoring structure surrounding the balloon, wherein the scoring structure is capable of scoring a luminal surface of a blood vessel upon inflation of the inflatable balloon; wherein the balloon catheter carries on at least on a portion of its surface a coating composition comprising at least one drug and at least one lipophilic antioxidant that will protect the at least one drug from premature loss during delivery to an angioplasty site and that is 3-100% by weight of the at least one drug, wherein the at least one drug is selected from the group consisting of a Limus drug, a cell proliferation inhibitor, and an inhibitor of neovascularization, wherein the at least one lipophilic antioxidant is selected from the group consisting of butylated hydroxytoluene, butylated hydroxyanisole, nordihydroguaiaretic acid, ascorbyl palmitate, and propyl gallate, and wherein a combination of a Limus drug with butylated hydroxytoluene as the lipophilic antioxidant is excluded.

2. The balloon catheter according to claim 1, wherein the scoring structure comprises one or more wires capable of scoring the luminal surface upon inflation of the inflatable balloon.

3. The balloon catheter according to claim 1, wherein the at least one drug comprises an oxidation-insensitive taxane selected from the group consisting of paclitaxel, protaxel and docetaxel.

4. The balloon catheter according to claim 3, wherein the at least one lipophilic antioxidant is nordihydroguaiaretic acid.

5. The balloon catheter according to claim 3, wherein the oxidation-insensitive taxane is oxidation-insensitive paclitaxel.

6. The balloon catheter according to claim 5, wherein the at least one lipophilic antioxidant is nordihydroguaiaretic acid.

7. The balloon catheter according to claim 1, wherein the at least one lipophilic antioxidant is nordihydroguaiaretic acid.

8. The balloon catheter according to claim 1, wherein the amount of the at least one lipophilic antioxidant protects the at least one drug from premature loss during delivery to the angioplasty site.

9. The balloon catheter according to claim 1, wherein the at least one antioxidant load is up to 10 μg/mm2 of coated catheter surface.

10. The balloon catheter according to claim 9, wherein the at least one lipophilic antioxidant is nordihydroguaiaretic acid.

11. The balloon catheter according to claim 1, wherein the at least one lipophilic antioxidant is contained at a ratio of 5-100% by weight, in relation to 100% by weight of the at least one drug.

12. The balloon catheter according to claim 11, wherein the at least one lipophilic antioxidant is nordihydroguaiaretic acid and the at least drug comprises oxidation-insensitive paclitaxel.

13. The balloon catheter according to claim 1, wherein the at least one lipophilic antioxidant is contained at a ratio of 10-100% by weight, in relation to 100% by weight of the at least one drug.

14. The balloon catheter according to claim 13, wherein the at least one lipophilic antioxidant is nordihydroguaiaretic acid and the at least drug comprises oxidation-insensitive paclitaxel.

15. The balloon catheter according to claim 1, wherein the at least one lipophilic antioxidant is contained at a ratio of 20-100% by weight, in relation to 100% by weight of the at least one drug.

16. The balloon catheter according to claim 15, wherein the at least one lipophilic antioxidant is nordihydroguaiaretic acid and the at least drug comprises oxidation-insensitive paclitaxel.

17. The balloon catheter according to claim 1, wherein the at least one lipophilic antioxidant is contained at a ratio of 50-100% by weight, in relation to 100% by weight of the at least one drug.

18. The balloon catheter according to claim 17, wherein the at least one lipophilic antioxidant is nordihydroguaiaretic acid and the at least drug comprises oxidation-insensitive paclitaxel.

19. The balloon catheter according to claim 1, further comprising a coating composition including the therapeutically effective amount of at least one drug and an amount of at least one lipophilic antioxidant, wherein the coating composition is polymer-free.

20. The balloon catheter according to claim 19, wherein the at least one lipophilic antioxidant is nordihydroguaiaretic acid and the at least drug comprises oxidation-insensitive paclitaxel.

Description

Example 1

(1) Balloons for percutaneous transluminal coronary angioplasty type A (AngioSculpt 3.5-20 mm, AngioScore, Inc., Fremont Calif., YSA were coated either with paclitaxel alone or combined with iopromide (iodinated contrast agent according to WO 002/076509) or different amounts of butylated hydroxy-toluene (BHT); solvent:acetone/ethanol/H.sub.2O. Coated balloons were tested in respect of paclitaxel loss during the passage through a hemostatic valve, Medtronic Launcher JL 3.5 6F guiding catheter and one minute in stirred blood (37° C.). When admixed at sufficient concentration to the coating solution, BHT improved the adhesion of paclitaxel.

(2) TABLE-US-00001 Loss on the way Catheter to the lesion Coating solution labeling % of dose No additive 1 24 2 40 Iopromide as an additive; 3 49 ca. 0.5 mg/mg paclitaxel 4 34 BHT 5% = 0.05 mg BHT/mg 5 15 paclitaxel 6 26 BHT 24% = 0.24 mg BHT/ 7 10 mg paclitaxel 8 6

Example 2

(3) Balloons for percutaneous transluminal coronary angioplasty type A were coated either with paclitaxel alone or combined with iopromide (iodinated contrast agent according to WO 02/076509), see example 2, or butylated hydroxytoluene (BHT) or nordihydroguaj aretic acid. Coated balloons were tested in respect of paclitaxel loss during the passage through a hemostatic valve, a Medtronic Launcher JL 3.5 6F guiding catheter and in stirred blood (37° C.) for one minute. When admixed at sufficient concentration to the coating solution, lipophilic antioxidants improve the adhesion of paclitaxel whereas the release during balloon inflation in a coronary artery (determined in separate experiments) was not impaired.

(4) TABLE-US-00002 Loss on Residual the way to paclitaxel the lesion on balloons Coating solution Labeling % of dose % of dose No additive acetone/ethanol/H.sub.2O Control 32 no data 1, 2 Iopromide as an additive; Control 42 ~10  ca. 0.5 mg/mg paclitaxel; 3, 4 acetone/ethanol/H.sub.2O BHT 24% = 0.24 mg BHT/mg A 15.3 ± 9.5  11 paclitaxel; acetone/ethanol/H.sub.2O BHT 24% = 0.24 mg BHT/mg B 3.4 ± 4.8 13 paclitaxel; tetrahydrofuran/ ethanol/H.sub.2O Nordihydroguaiaretic acid C 4.2 ± 7.2 no data 35% = 0.35 mg/mg paclitaxel; acetone/ethanol/H.sub.2O