Apparatus and method for the local delivery of drugs

• US 6,352,683 B1
• Filed: 07/15/1997
• Issued: 03/05/2002
• Est. Priority Date: 01/19/1995
• Status: Expired due to Fees

• Current Assignee: University of Pittsburgh of The Commonwealth System of Higher Education
• Original Assignee: POINT Biomedical Corporation
• Inventors: ten Cate, Folkert Jan
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): Joynes, Robert M.
• Application Number:
  US08/893,206
• Time in Patent Office: 1,694 Days
• Field of Search: 600/470, 600/467, 600/453, 424/450, 424/9.3, 424/9.32, 424/9.51, 424/9.52
• US Class Current: 424/9.34
• CPC Class Codes: A61K 41/00 Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
• CPC Class Codes: A61K 47/6921 the form being a particulate, a powder, an adsorbate, a bead or a sphere
• CPC Class Codes: A61K 49/223 Microbubbles, hollow microspheres, free gas bubbles, gas microspheres

Abstract

A local and site-specific drug delivery apparatus for delivering a drug to a specific site is characterized by the combination of a carrier material which reflects or absorbs or emits electromagnetic or mechanical (e.g. ultrasonic) vibrations enabling the monitoring of the material, a drug associated with the carrier material, and a local-delivery mechanism for delivering the carrier material and the drug to a specific site. The local-delivery mechanism may comprise a local-delivery catheter, such as a balloon-type catheter, and the drug delivery apparatus may additionally include a monitor for monitoring the delivery of the drug to the specific site, such as an ultrasonic imaging system. The drug delivery apparatus may also include a vibration generator for inducing release of the drug from the carrier material when the carrier material is at the specific site, such as a generator of ultrasonic energy. Alternatively, the local-delivery mechanism may comprise a targeting agent associated with the carrier material, the targeting agent capable of binding to the specific site within the individual. The targeting agent may be a protein or an antibody, such as a glycogen IIa/IIB receptor antibody, Von Willebrand'"'"'s factor antibody, an antitumor antibody, hepatic cellular antibody, a white blood cell antibody, or antifibrin.

Claims

1. A system for delivering a drug to a specific site and for monitoring the drug at the specific site, said system comprising:

a carrier material which reflects or absorbs or emits electromagnetic or mechanical vibrations enabling the monitoring of said carrier material, said carrier material comprising an ultrasonic contrast agent composed of microbubbles having a diameter of between 1-1000 μ

m;

a drug carried by said carrier material;

a local-delivery catheter having said carrier material disposed therein and said drug carried by said carrier material disposed therein, said local-delivery catheter being designed such that said carrier material and said drug may be delivered to said specific site, said local-delivery catheter being designed so as to force said carrier material and said drug into an internal blood vessel wall at said specific site so that said carrier material and said drug are trapped therein;

an ultrasonic imaging system that detects said carrier material at said specific site to confirm the presence of said carrier material at said specific site; and

vibration generator associated with said imaging system, said vibration generator generating electromagnetic or mechanical vibrations that induce release of said drug from said carrier material when said carrier material is at said specific site by causing said microbubbles to collapse.

2. A system as defined in claim 1 wherein said carrier material comprises an ultrasonic contrast agent composed of microbubbles having a diameter of between 1-100 μ

m.

3. A system as defined in claim 1 wherein said local-delivery catheter comprises a balloon catheter.

4. A system for delivering a drug to a specific site and for monitoring the drug at the specific site, said system comprising:

a carrier material which reflects or absorbs or emits electromagnetic or mechanical vibrations enabling the monitoring of said carrier material, said carrier material comprising microparticles, microbubbles, microspheres or microcapsules;

a drug carried by said carrier material;

a local-delivery catheter having said carrier material disposed therein and said drug carried by said carrier material disposed therein, said local-delivery catheter being designed such that said carrier material and said drug may be delivered to said specific site, said localdelivery catheter being designed so as to force said carrier material and said drug into an internal blood vessel wall at said specific site so that said carrier material and said drug are trapped therein;

an imaging system that detects said carrier material at said specific site to confirm the presence of said carrier material at said specific site; and

an apparatus associated with said imaging system, said apparatus generating electromagnetic or mechanical vibrations that induce release of said drug from said carrier material when said carrier material is at said specific site.

5. A system as defamed in claim 4 wherein said carrier material comprises an ultrasonic contrast agent composed of microbubbles.

6. A system as defined in claim 4 wherein said local-delivery catheter comprises a balloon catheter.

7. A system as defined in claim 4 wherein said imaging system comprises an ultrasonic imaging system.

8. A method of delivering a carrier material and a drug to a specific site using a local-delivery catheter and monitoring the carrier material and drug at the specific site, said method comprising the steps of:

(a) disposing a carrier material which reflects or absorbs or emits electromagnetic or mechanical vibrations enabling the monitoring of said carrier material and a drug carried by said carrier material within a local-delivery catheter that is capable of delivering said carrier material and said drug to a specific site within a blood vessel, said carrier material comprising an ultrasonic contrast agent composed of microbubbles having a diameter of between 1-1000 μ

m;

(b) after said carrier material and said drug are disposed within said local delivery catheter in said step (a), inserting said local-delivery catheter in said blood vessel;

(c) when said local-delivery catheter is disposed within said blood vessel, using said local-delivery catheter to force said carrier material and said drug into an internal wall of said blood vessel at said specific site so that said carrier material and said drug are trapped at said specific site;

(d) while said carrier material and said drug are trapped at said specific site in said blood vessel, using an imaging system to generate an image of said carrier material at said specific site in said blood vessel to confirm the presence of said carrier material at said specific site in said blood vessel; and

(e) after the presence of said carrier material at said specific site in said blood vessel is confirmed at said step (d), generating electromagnetic or mechanical vibrations that induce release of said drug from said carrier material when said carrier material is at said specific site in said blood vessel by causing said microbubbles to collapse.

9. A method as defined in claim 8 wherein said step (a) comprises the step of disposing an ultrasonic contrast agent composed of microbubbles having a diameter of between 1-100 μ

m within said local delivery catheter.

10. A method as defined in claim 8 wherein said step (a) comprises the step of disposing said carrier material and said drug in a balloon catheter.

11. A method as defined in claim 8 wherein said step (d) comprises the step of detecting the presence of said carrier material at said specific site with an ultrasonic imaging system.

12. A method of delivering a carrier material and a drug to a specific site using a local-delivery catheter and monitoring the carrier material and drug at the specific site, said method comprising the steps of:

(a) disposing a carrier material which reflects or absorbs or emits electromagnetic or mechanical vibrations enabling the monitoring of said carrier material and a drug carried by said carrier material within a local-delivery catheter that is capable of delivering said carrier material and said drug to a specific site within a blood vessel, said carrier material comprising microparticles, microbubbles, microspheres or microcapsules;

(b) after said carrier material and said drug are disposed within said local delivery catheter in said step (a), inserting said local-delivery catheter in said blood vessel;

(c) when said local-delivery catheter is disposed within said blood vessel, using said local-delivery catheter to force said carrier material and said drug into an internal wall of said blood vessel at said specific site so that said carrier material and said drug are trapped at said specific site;

(d) while said carrier material and said drug are trapped at said specific site in said blood vessel, using an imaging system to generate an image of said carrier material at said specific site in said blood vessel to confirm the presence of said carrier material at said specific site in said blood vessel; and

(e) after the presence of said carrier material at said specific site in said blood vessel is confirmed at said step (d), generating electromagnetic or mechanical vibrations that induce release of said drug from said carrier material when said carrier material is at said specific site in said blood vessel.

13. A method as defamed in claim 12 wherein said step (a) comprises the step of disposing an ultrasonic contrast agent composed of microbubbles.

14. A method as defamed in claim 12 wherein said step (a) comprises the step of disposing said carrier material and said drug in a balloon catheter.

15. A method as defamed in claim 12 wherein said step (d) comprises the step of detecting the presence of said carrier material at said specific site with an ultrasonic imaging system.