Method of coating 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 oxidation-insensitive drug or oxidation-insensitive polymer free 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 the at least one oxidation-insensitive drug is selected of taxes, thalidomide, statins, corticoids and lipophilic derivatives of corticoids, and the at least one lipophilic antioxidant is selected of nordihydroguaiaretic acid, resveratrol and propyl gallate.

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; an inflatable balloon coupled to the shaft; and a nonimplantable scoring structure surrounding the inflatable balloon; and spraying a coating composition onto at least a portion of a surface of the balloon catheter, wherein the coating composition comprises a therapeutically effective amount of at least one oxidation-insensitive drug and an amount of nordihydroguaiaretic acid, wherein the nordihydroguaiaretic acid protects the at least one oxidation-insensitive drug from premature loss during delivery to an angioplasty site, wherein the amount of nordihydroguaiaretic acid is 3-100% by weight of the at least one oxidation-insensitive drug, wherein the at least one oxidation-insensitive drug is selected from the group consisting of: taxanes, thalidomide, statins, corticoids and lipophilic derivatives of corticoids.

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

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

4. The method according to claim 1, wherein the at least one oxidation-insensitive drug is a taxane selected from the group consisting of paclitaxel, protaxel and docetaxel.

5. The method according to claim 4, wherein the taxane is paclitaxel.

6. The method according to claim 1, wherein the amount of nordihydroguaiaretic acid includes up to 10 g/mm.sup.2 of the surface of the inflatable balloon.

7. The method according to claim 1, wherein the amount of nordihydroguaiaretic acid is at a ratio of 20-100% by weight, in relation to 100% by weight of the at least one oxidation-insensitive drug.

8. The method according to claim 1, wherein the amount of nordihydroguaiaretic acid is at a ratio of 50-100% by weight, in relation to 100% by weight of the at least one oxidation-insensitive drug.

9. The method according to claim 1, wherein the coating composition is polymer-free.

10. 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; an inflatable balloon coupled to the shaft, wherein the inflatable balloon has a surface; and a nonimplantable cutting structure surrounding the inflatable balloon; and spraying a coating composition onto at least a portion of the surface of the inflatable balloon, wherein the coating composition comprises a therapeutically effective amount of at least one oxidation-insensitive drug and an amount of nordihydroguaiaretic acid capable of protecting the at least one oxidation-insensitive drug from premature loss during delivery to an angioplasty site, wherein the nordihydroguaiaretic acid is 3-100% by weight of the drug, wherein the at least one oxidation-insensitive drug is selected from the group consisting of: taxanes, thalidomide, statins, corticoids and lipophilic derivatives of corticoids.

11. The method according to claim 10, wherein the at least one drug comprises oxidation-insensitive paclitaxel.

12. 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; an inflatable balloon coupled to the shaft, wherein the inflatable balloon has a surface; and a nonimplantable scoring structure surrounding the inflatable balloon; and spraying a coating composition onto at least a portion of the surface of the inflatable balloon, wherein the coating composition comprises a therapeutically effective amount of an oxidation-insensitive taxane drug and an amount of nordihydroguaiaretic acid that protects the oxidation-insensitive taxane drug from premature loss during delivery to an angioplasty site, wherein the nordihydroguaiaretic acid is at a ratio of 20-100% by weight, in relation to 100% by weight of the oxidation-insensitive taxane drug.

13. The method according to claim 12, wherein the scoring structure comprises one or more wires capable of scoring a luminal surface of a blood vessel upon inflation of the inflatable balloon.

14. The method according to claim 12, wherein the oxidation-insensitive taxane drug is selected from the group consisting of paclitaxel, protaxel and docetaxel.

15. The method according to claim 14, wherein the amount of nordihydroguaiaretic acid comprises up to 10 g/mm.sup.2 of the surface of the inflatable balloon.

16. The method according to claim 12, wherein the oxidation-insensitive taxane is paclitaxel.

17. The method according to claim 16, wherein the amount of nordihydroguaiaretic acid comprises up to 10 g/mm.sup.2 of the surface of the inflatable balloon.

18. The method according to claim 12, wherein the amount of nordihydroguaiaretic acid comprises up to 10 g/mm.sup.2 of the surface of the inflatable balloon.

Description

EXAMPLE 1

(1) 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/H20. 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 Catheter Loss on the way to the Coating solution Labeling lesion % of dose No additive 1 24 2 40 Iopromide as an additive; ca. 3 49 0.5 mg/mg paclitaxel 4 34 BHT 5% = 0.05 mg 5 15 BHT/mg paclitaxel 6 26 BHT 24% = 0.24 mg 7 10 BHT/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 nordihydroguaiaretic acid.

(4) 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.

(5) TABLE-US-00002 Loss on the Residual way to the paclitaxel lesion % of on balloons Coating solution Labeling dose % of dose No additive acetone/ethanol/ Control 32 No data H.sub.2O 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 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 Nordihydroguaiaretic C 4.2 7.2 No data acid 35% = 0.35 mg/ mg paclitaxel; acetone/ethanol/H.sub.2O

EXAMPLE 3

(6) Balloons for percutaneous transluminal coronary angioplasty type A were coated either with paclitaxel without resveratrol or combined with resveratrol. Coated balloons were tested in respect of paclitaxel loss as described in example 1. When admixed at sufficient concentration to the coating solution, resveratrol improved the adhesion of paclitaxel.

(7) TABLE-US-00003 Loss on the way to the Coating solution Labeling lesion % of dose Resveratrol 0% acetone/ Control 25 8 tetrahydrofuran/H.sub.2O Resveratrol 20% = 0.2 N 21 6 mg/mg paclitaxel; acetone/ tetrahydrofuran/H.sub.2O Resveratrol 50% = 0.5 O 7 11 mg/mg paclitaxel; acetone/ tetrahydrofuran/H.sub.2O

EXAMPLE 4

(8) Balloons for percutaneous transluminal coronary angioplasty type A were coated in already folded condition either with paclitaxel without or with polyacrylic acid. Polyacrylic acid (molecular weight about 6000 D (Polysciences Inc., USA) and glycerol improved the homogeneity of the coating on the balloon.

(9) TABLE-US-00004 Coating solution Labeling Distribution on balloons Paclitaxel without polyacrylic N Spreading limited to acid acetone/tetrahydrofuran/ directly accessible surface H.sub.2O 0.8 mg polyacrylic acid + D Irregular distribution, 0.06 mg glycerol/mg paclitaxel partly below the folds acetone/tetrahydrofuran/H.sub.2O 0.15 mg polyacrylic acid + E Almost homogeneous 0.06 mg glycerol/mg paclitaxel distribution including in acetone/tetrahydrofuran/H.sub.2O areas below the folds