Drug releasing coatings for medical devices

• US 8,414,910 B2
• Filed: 03/25/2010
• Issued: 04/09/2013
• Est. Priority Date: 11/20/2006
• Status: Active Grant

• Current Assignee: Lutonix, Inc. (Becton, Dickinson & Co)
• Original Assignee: Lutonix, Inc. (Becton, Dickinson & Co)
• Inventors: Wang, Lixiao
• Primary Examiner(s): ZISKA, SUZANNE E
• Application Number:
  US12/731,835
• Publication Number:
  US 20100209472A1
• Time in Patent Office: 1,111 Days
• Field of Search: None
• US Class Current: 424/423
• CPC Class Codes: A61F 2/844 folded prior to deployment
• CPC Class Codes: A61F 2/958 Inflatable balloons for placing stents or stent-grafts
• 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 31/337 having four-membered rings, e.g. taxol
• 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: A61L 2300/416 Anti-neoplastic or anti-proliferative or anti-restenosis or anti-angiogenic agents, e.g. paclitaxel, sirolimus
• CPC Class Codes: A61L 2300/428 Vitamins, e.g. tocopherol, riboflavin
• CPC Class Codes: A61L 2300/606 Coatings
• CPC Class Codes: A61L 2300/608 having two or more layers
• CPC Class Codes: A61L 2300/802 Additives, excipients, e.g. cyclodextrins, fatty acids, surfactants
• CPC Class Codes: A61L 29/08 Materials for coatings
• CPC Class Codes: A61L 29/085 Macromolecular materials
• CPC Class Codes: A61L 29/16 Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence
• CPC Class Codes: A61L 31/08 Materials for coatings
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: A61M 2025/105 having a balloon suitable for drug delivery, e.g. by using holes for delivery, drug coating or membranes
• CPC Class Codes: A61M 25/10 Balloon catheters A61M25/0125 takes precedence; embolectomy A61B17/22032; retractors A61B17/02; inflatable balloons for placing stents or stent-grafts A61F2/958 ; stomach balloons for treatment of obesity A61F5/0003; oesophagal tubes A61J15/00

Abstract

The invention relates to a medical device for delivering a therapeutic agent to a tissue. The medical device has a layer overlying the exterior surface of the medical device. The layer contains a therapeutic agent, an antioxidant, and an additive. In certain embodiments, the additive has a hydrophilic part and a drug affinity part, wherein the drug affinity part is at least one of a hydrophobic part, a part that has an affinity to the therapeutic agent by hydrogen bonding, and a part that has an affinity to the therapeutic agent by van der Waals interactions. In some embodiments, the additive is a liquid. In other embodiments, the additive is at least one of a surfactant and a chemical compound, and the chemical compound has one or more hydroxyl, amino, carbonyl, carboxyl, acid, amide or ester groups.

Claims

1. A balloon catheter for delivering a therapeutic agent to a target site of a blood vessel, the balloon catheter comprising:

a coating layer overlying an exterior surface of a balloon, wherein;

the coating layer comprises an initial drug load of a hydrophobic therapeutic agent, and a combination of a water-soluble first additive and a water-soluble second additive;

the hydrophobic therapeutic agent is selected from the group consisting of paclitaxel, rapamycin, and combinations thereof;

the water-soluble first additive is selected from the group consisting of PEG sorbitan monolaurates, PEG sorbitan monooleates, and combinations thereof;

the water-soluble second additive is selected from the group consisting of sorbitol, sorbitan, xylitol, gluconolactone, and combinations thereof.

2. The balloon catheter of claim 1, wherein the ratio by weight of the therapeutic agent in the coating layer to the total weight of the first and second additives in the coating layer is from about 0.5 to 3.

3. The balloon catheter of claim 1, wherein the initial drug load is from 1 μ

g to 20 μ

g of the hydrophobic therapeutic agent per square millimeter of the balloon.

4. The balloon catheter of claim 1, wherein:

the water-soluble first additive is selected from the group consisting of PEG-20 sorbitan monolaurate, PEG-20 sorbitan monooleate, and combinations thereof.

5. The balloon catheter of claim 1, wherein:

the water-soluble first additive is selected from the group consisting of PEG-20 sorbitan monolaurate, PEG-20 sorbitan monooleate, and combinations thereof; and

the water-soluble second additive is selected from the group consisting of sorbitol, gluconolactone, and combinations thereof.

6. The balloon catheter of claim 1, wherein:

the water-soluble first additive is PEG-20 sorbitan monolaurate or PEG-20 sorbitan monooleate; and

the water-soluble second additive is selected from the group consisting of sorbitol, xylitol, gluconolactone, and combinations thereof.

7. The balloon catheter of claim 1, wherein:

the hydrophobic therapeutic agent is paclitaxel;

the water-soluble first additive is PEG-20 sorbitan monolaurate;

the water-soluble second additive is sorbitol; and

the balloon catheter has initial drug load of from 2 μ

g to 6 μ

g of the hydrophobic therapeutic agent per square millimeter of the balloon.

8. The balloon catheter of claim 7, wherein the ratio by weight of the hydrophobic therapeutic agent in the coating layer to the total weight of the water-soluble first and second additives in the coating layer is from about 0.1 to 5.

9. A balloon catheter for delivering a therapeutic agent to a target site of a blood vessel, the balloon catheter comprising:

a coating layer overlying an exterior surface of a balloon, wherein;

the coating layer comprises a water-soluble first additive, a water-soluble second additive, and a hydrophobic therapeutic agent with an initial drug load of from 2 μ

g to 6 μ

g of the hydrophobic therapeutic agent per square millimeter of the balloon;

the hydrophobic therapeutic agent is selected from the group consisting of paclitaxel, rapamycin, and combinations thereof;

the hydrophobic therapeutic agent is not enclosed in micelles or liposomes and is not encapsulated in polymer particles;

the water-soluble first additive is selected from the group consisting of PEG-20 sorbitan monolaurate and PEG-20 sorbitan monooleate, and combinations thereof;

the water-soluble second additive is selected from the group consisting of sorbitol, xylitol, gluconolactone, lactobionic acid, and combinations thereof; and

the ratio by weight of the hydrophobic therapeutic agent in the coating layer to the total weight of the water-soluble first and second additives in the coating layer is from about 0.1 to 5.

10. The balloon catheter of claim 9, wherein:

the water-soluble first additive is PEG-20 sorbitan monolaurate; and

the water-soluble second additive is gluconolactone.

11. The balloon catheter of claim 9, wherein:

the water-soluble first additive is PEG-20 sorbitan monolaurate; and

the water-soluble second additive is sorbitol or xylitol.

12. The balloon catheter of claim 9, wherein:

the water-soluble first additive is PEG-20 sorbitan monolaurate; and

the water-soluble second additive is lactobionic acid.

13. The balloon catheter of claim 9, wherein:

the water-soluble first additive is PEG-20 sorbitan monooleate; and

the water-soluble second additive is gluconolactone.

14. The balloon catheter of claim 9, wherein:

the water-soluble first additive is PEG-20 sorbitan monooleate; and

the water-soluble second additive is sorbitol or xylitol.

15. A balloon catheter for delivering a therapeutic agent to a target site of a blood vessel, the balloon catheter comprising:

a coating layer overlying an exterior surface of a balloon, wherein;

the coating layer comprises a water-soluble first additive, a water-soluble second additive, and an initial drug load of a hydrophobic therapeutic agent;

the hydrophobic therapeutic agent is selected from the group consisting of paclitaxel, rapamycin, and combinations thereof;

the water-soluble first additive is selected from the group consisting of PEG-20 sorbitan monolaurate, PEG-20 sorbitan monooleate, and combinations thereof;

the water-soluble second additive is selected from the group consisting of sorbitol, xylitol, gluconolactone, lactobionic acid, and combinations thereof,

whereby the combination of the water-soluble first additive and the water-soluble second additive promotes a rapid release of the hydrophobic therapeutic agent from the balloon, and whereby the rapid release comprises a residual drug amount of the hydrophobic therapeutic agent remaining on the balloon after the balloon is inflated at the target site of the blood vessel for an inflation period of from about 0.1 minutes to 2 minutes and subsequently removed from the blood vessel.

16. The balloon catheter of claim 15, wherein:

the initial drug load is from 2 μ

g to 6 μ

g of the hydrophobic therapeutic agent per square millimeter of the balloon; and

the residual drug amount is 24.7% or less of the initial drug load.

17. The balloon catheter of claim 16, wherein the water-soluble first additive is PEG-20 sorbitan monolaurate.

18. The balloon catheter of claim 16, wherein the water-soluble second additive is sorbitol or gluconolactone.