Triggered release hydrogel drug delivery system

• US 6,524,274 B1
• Filed: 06/07/1995
• Issued: 02/25/2003
• Est. Priority Date: 12/28/1990
• Status: Expired due to Fees

• Current Assignee: Boston Scientific Scimed (Boston Scientific Corporation)
• Original Assignee: Scimed Life Systems Incorporated (Boston Scientific Corporation)
• Inventors: Rosenthal, Arthur, Barry, James J., Sahatjian, Ronald
• Primary Examiner(s): Sykes, Angela D.
• Assistant Examiner(s): Bianco, Patricia
• Application Number:
  US08/478,745
• Time in Patent Office: 2,820 Days
• Field of Search: 604/19, 604/27-28, 604/47-48, 604/500, 604/506-509, 604/514, 604/518, 604/522, 604/96.01, 604/103-1-1, 604/103-7-1, 604/113-114, 604/264-265, 604/523, 604/289-290, 606/191, 606/192, 606/194-195, 606/198, 600/433-435, 427/2.1, 427/2.22, 427/2-2-, 427/2-4-, 427/2.3
• US Class Current: 604/96.01
• CPC Class Codes: A61F 2/90 characterised by a net-like or mesh-like structure
• CPC Class Codes: A61F 2250/0067 Means for introducing or releasing pharmaceutical products into the body
• 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 2300/42 Anti-thrombotic agents, anticoagulants, anti-platelet agents
• CPC Class Codes: A61L 2300/602 Type of release, e.g. controlled, sustained, slow
• CPC Class Codes: A61L 29/085 Macromolecular materials
• CPC Class Codes: A61L 29/145 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 29/16 Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: A61L 31/145 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: A61M 16/0443 Special cuff-wall materials A61M16/0481, A61M16/0422 take precedence
• CPC Class Codes: A61M 16/0456 one cuff within another
• CPC Class Codes: A61M 16/0481 through the cuff wall
• CPC Class Codes: A61M 2025/0057 Catheters delivering medicament other than through a conventional lumen, e.g. porous walls or hydrogel coatings
• CPC Class Codes: A61M 2025/09183 having tools at the distal tip
• CPC Class Codes: A61M 2025/1013 with concentrically mounted balloons, e.g. being independently inflatable
• 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 2025/1086 having a special balloon surface topography, e.g. pores, protuberances, spikes or grooves
• CPC Class Codes: A61M 2205/0266 Shape memory materials
• CPC Class Codes: A61M 25/0045 : multi-layered, e.g. coated coating materials A61L29/08
• CPC Class Codes: A61M 25/104 : used for angioplasty
• CPC Class Codes: C08L 33/02 : Homopolymers or copolymers of acids; Metal or ammonium salts thereof

Abstract

The invention features a method for triggering release of a drug from a hydrogel polymer to tissue at a desired location of the body using a catheter. A portion of the catheter is coated on its outer surface with a polymer having the capacity to incorporate a predetermined substantial amount of drug which is immobilized in the polymer until released by a triggering agent or condition that is different from physiological conditions. Upon contact with a triggering agent or condition, the polymer reacts, e.g., swells or contracts, such that the drug is delivered to the desired body tissue. A balloon catheter is shown in which the hydrogel is carried on the exterior surface of the balloon.

Claims

1. A method for delivering a drug to tissue at a desired location within the body, comprising:

providing a drug substantially immobilized in a hydrogel;

providing a solution comprising a triggering agent that differs from ambient physiological conditions;

providing a catheter constructed for insertion in the body, a portion of said catheter carrying said hydrogel with a predetermined substantial amount of said drug incorporated therein;

introducing said catheter to the body at the point of desired drug application; and

exposing said hydrogel to said triggering agent.

2. The method of claim 1, wherein exposing said hydrogel to said triggering agent increases local ionic strength, thereby triggering release of said drug from said hydrogel.

3. The method of claim 2, wherein said drug is associated with said hydrogel by an ionic interaction and exposing said hydrogel to said triggering agent disrupts said ionic interaction.

4. The method of claim 3, wherein said triggering agent is a saline solution having a molarity of at least 0.2 molar.

5. The method of claim 3, wherein said drug is cationic and said hydrogel is anionic.

6. The method of claim 3, wherein said drug is anionic and said hydrogel is cationic.

7. The method of claim 1, wherein said triggering agent is a solution with a pH that induces a volume phase transition of said hydrogel, thereby triggering release of said drug.

8. The method of claim 6, wherein said solution has a pH of greater than about 7.5.

9. The method of claim 6, wherein said solution has a pH of less than about 7.3.

10. The method of claim 1, wherein said drug is an anti-proliferative drug.

11. The method of claim 1, wherein said drug is an anti-thrombogenic drug.

12. The method of claim 1, wherein said drug is a thrombolytic drug.

13. A method for triggering release of a drug from a hydrogel to a tissue at a desired location of a wall of a body lumen, comprising:

providing a drug substantially immobilized in a hydrogel;

providing a solution comprising a triggering agent that differs from ambient physiological conditions;

providing a catheter constructed for insertion in a body lumen having a catheter shaft with an expandable balloon portion mounted on said catheter shaft;

said balloon portion being expandable to engage the tissue at a controlled pressure to fill a cross-section of the body lumen and press against the wall of the body lumen;

said balloon portion being coated on its outer surface with said hydrogel;

introducing said catheter to the body lumen wherein said balloon portion is positioned at the point of desired drug application;

expanding said balloon portion to engage the tissue; and

exposing said hydrogel to said triggering agent.

14. A method for delivering a drug to tissue at a desired location within the body, comprising:

providing a drug substantially immobilized in a hydrogel, wherein said hydrogel is a photo-sensitive polymer comprising a photosensitive compound;

providing a catheter constructed for insertion in the body, a portion of said catheter carrying said hydrogel having the capacity to incorporate a predetermined substantial amount of said drug;

introducing said catheter to the body at the point of desired drug application; and

illuminating said hydrogel with visible or ultraviolet light.

15. The method of claim 14, wherein said photosensitive compound comprises a porphyrin ring.

16. The method of claim 14, wherein said photosensitive compound is selected from the group consisting of rhodamine, chlorophyllin, leucocyanide, and leucohydroxide.