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 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 taxanes, 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 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 therapeutically effective amount of at least one oxidation-insensitive drug and an amount of a lipophilic antioxidant that will protect the drug from premature loss during delivery to the angioplasty site and that 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, and the lipophilic antioxidant is nordihydroguaiaretic acid.

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 oxidation-insensitive drug is a taxane selected from the group consisting of paclitaxel, protaxel and docetaxel.

4. The balloon catheter according to claim 3, wherein the taxane is paclitaxel.

5. The balloon catheter according to claim 1, wherein the ene antioxidant load is up to 10 g/mm.sup.2 of coated catheter surface and the antioxidant is provided at a dose level that provides no therapeutic or prophylactic effect.

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

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

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

9. 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 cutting structure surrounding the balloon, wherein the cutting structure is capable of cutting 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 therapeutically effective amount of at least one oxidation-insensitive drug and an amount of a lipophilic antioxidant that will protect the drug from premature loss during delivery to the angioplasty site and that 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, and the lipophilic antioxidant is nordihydroguaiaretic acid.

10. The balloon catheter according to claim 9, wherein the at least one drug comprises oxidation-insensitive paclitaxel.

11. 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, wherein the inflatable balloon comprises a surface, wherein at least a portion of the surface carries 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; and a nonimplantable scoring structure surrounding the balloon, wherein the nonimplantable scoring structure is capable of scoring a luminal surface of a blood vessel upon inflation of the inflatable balloon.

12. The balloon catheter according to claim 11, wherein the scoring structure comprises one or more wires capable of scoring the luminal surface upon inflation of the inflatable balloon.

13. The balloon catheter according to claim 11, wherein the oxidation-insensitive taxane drug is selected from the group consisting of paclitaxel, protaxel and docetaxel.

14. The balloon catheter according to claim 13, wherein the taxane is paclitaxel.

15. The balloon catheter according to claim 11, wherein the nordihydroguaiaretic acid load comprises up to 10 g/mm.sup.2 of coated catheter surface.

Description

(1) Below, the invention is described by means of Examples.

EXAMPLE 1

(2) Balloons for percutaneous transluminal coronary angioplasty type A (AngioSculpt 3.5-20 mm, AngioScore, Inc., Fremont Calif., USA) were coated either with aclitaxel alone or combined with iopromide (iodinated contrast agent according to WO 02/076509) or different amounts of butylated hydroxy-toluene (BHT); solvent: acetone/ethanol/H2O. 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.

(3) 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 BHT/mg 5 15 paclitaxel 6 26 BHT 24% = 0.24 mg BHT/mg 7 10 paclitaxel 8 6

EXAMPLE 2

(4) 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.

(5) 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.

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

(7) 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.

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

EXAMPLE 4

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

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