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 method of manufacturing a medical device for use in angioplasty or coronary angioplasty, comprising: providing a balloon catheter, the balloon catheter 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; and spraying a coating composition onto at least a portion of a surface of the balloon catheter, the coating composition comprising at least one drug and at least one lipophilic antioxidant, the coating composition being 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, wherein a combination of a Limus drug with butylated hydroxytoluene as the lipophilic antioxidant is excluded, wherein the at least one lipophilic antioxidant protects the at least one drug from premature loss.

2. The method according to claim 1, wherein the scoring structure comprises one or more wires.

3. The method according to claim 1, wherein the coating composition is sprayed onto the inflatable balloon.

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

5. The method according to claim 4, wherein the at least one lipophilic antioxidant is nordihydroguaiaretic acid.

6. The method according to claim 4, wherein the oxidation-insensitive taxane is oxidation-insensitive paclitaxel.

7. The method according to claim 6, wherein the at least one lipophilic antioxidant is nordihydroguaiaretic acid.

8. The method according to claim 3, wherein the at least one lipophilic antioxidant is nordihydroguaiaretic acid.

9. The method according to claim 3, wherein the at least one antioxidant load is up to 10 g/mm.sup.2 of the surface.

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

11. The method 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 method 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 method 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 method 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 method 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 method 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 method 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 method 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 method according to claim 1, wherein the balloon catheter further comprises 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 method 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

[0028] Balloons for percutaneous transluminal coronary angioplasty type A (AngioSculpt 3.5-20 mm, AngioScore, Inc., Fremont Calif., USA were coated either with paclitaxel alone or combined with iopromide (iodinated contrast agent according to WO 02/076509) 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.

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

EXAMPLE 2

[0029] 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 arctic 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.

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