Implantable Medical Device with Apertures for Delivery of Bioactive Agents

• US 20080081064A1
• Filed: 09/28/2007
• Published: 04/03/2008
• Est. Priority Date: 09/28/2006
• Status: Abandoned Application

• Current Assignee: Surmodics Incorporated
• Original Assignee: Surmodics Incorporated
• Inventors: Wall, John, Jelle, Bruce, Anderson, Aron
• Application Number:
  US11/904,925
• Publication Number:
  US 20080081064A1
• Time in Patent Office: Days
• US Class Current: 424/426
• CPC Class Codes: A61F 2250/0068 the pharmaceutical product being in a reservoir
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61K 9/0092 Hollow drug-filled fibres, tubes of the core-shell type, coated fibres, coated rods, microtubules or nanotubes
• CPC Class Codes: A61L 2300/45 Mixtures of two or more drugs, e.g. synergistic mixtures
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 27/56 Porous materials, e.g. foams or sponges
• CPC Class Codes: A61L 31/146 Porous materials, e.g. foams or sponges
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

An implantable medical device for the release of bioactive agents at desired rates is described. The device includes a body member with two or more aperture sets and an inner space. The bioactive agents are arranged within the inner space of the body member so that each bioactive agent present in the inner space is individually releasable through their respective aperture set. The aperture sets modulate the release of the bioactive agents from the body member. Arrangement of apertures and bioactive agents within the inner portion chosen to provide desired and independent release rates from the device.

Claims

1. An implantable device for the delivery of at least two bioactive agents to a subject, the device comprising:

a body member comprising

a first set of apertures,

a second set of apertures, and

an inner space comprising

an amount of a first bioactive agent, and

an amount of a second bioactive agent,

wherein, during implantation in a subject, the majority of the amount of the first bioactive agent is releasable from the device through the first set of apertures, and the majority of the amount of the second bioactive agent is releasable from the device through the second set of apertures.

2. The device of claim 1 wherein the body member comprises a biodegradable polysaccharide.

3. The device of claim 1 wherein the first and second sets comprise one or more apertures.

4. The device of claim 1 wherein an aperture has an area of 12.5 mm² or less on average.

5. The device of claim 1 wherein an aperture has an area in the range of 3×

10³ μ

m² to 3.25×

10⁵ μ

m².

6. The device of claim 1 wherein the apertures comprise a material that is dissolvable or degradable during implantation in a subject.

7. The device of claim 1 comprising a total aperture area and a total body member surface area, and the ratio of the total aperture area to the total body member area is 2:

3 or less.

8. The device of claim 7 wherein the ratio of the total aperture area to the total body member area is in the range of 1:

10 to 1;

207.

9. The device of claim 1 wherein the first set of apertures has a total aperture area that is less than a total aperture area of a second set of apertures.

10. The device of claim 1 wherein the inner space comprises at least one polymeric matrix, and the first bioactive agent and second bioactive agent are present in the at least one polymeric matrix.

11. The device of claim 10 wherein the at least one polymeric matrix comprises a biodegradable polysaccharide.

12. The device of claim 1 wherein the first bioactive agent is hydrophilic.

13. The device of claim 1 wherein the second bioactive agent is hydrophobic.

14. The device of claim 1 wherein the first bioactive agent comprises a polypeptide.

15. The device of claim 1 wherein the second bioactive agent has a molecular weight of less than 1000 Da.

16. The device of claim 1 wherein the first bioactive agent is water-soluble and the second bioactive agent is poorly soluble, or not soluble in water.

17. A method for forming an implantable bioactive agent delivery device comprising steps of:

obtaining a body member comprising

a first set of apertures,

a second set of apertures, and

an inner space;

providing a first bioactive agent to a portion of the inner space so the first bioactive agent is primarily releasable through the first set of apertures during implantation of the device in a subject; and

providing a second bioactive agent to a portion of the inner space so the second bioactive agent is primarily releasable through the second set of apertures during implantation of the device in a subject.

18. A method for delivering two or more bioactive agents to a subject comprising steps of

implanting at a target location in the body an implantable bioactive agent delivery device comprising:

a body member comprising

a first set of apertures, and

a second set of apertures; and

an inner space comprising

a first bioactive agent, and

a second bioactive agent;

wherein the first bioactive agent and the second bioactive agent are substantially unmixed in the inner space, and

allowing release of the first bioactive agent through the first set of apertures and release of the second bioactive agent through the second set of apertures in the body.

19. The method of claim 18 wherein the step of allowing release, the first bioactive agent has a rate of release that is less than the rate of release of the second bioactive agent

20. The method of claim 19 wherein the step of allowing release, the rate of release of the first bioactive agent is modulated by the first set of apertures having a total aperture area less than a total aperture area of a second set of apertures.

21. The method of claim 18 wherein the step of implanting, the first bioactive agent is present in a first polymeric matrix and the second bioactive agent is present in a second polymeric matrix.

22. The method of claim 21 wherein the step of allowing release, the rate of release of the first bioactive agent is modulated by a first polymeric matrix having a degree of crosslinking that is higher than the second polymeric matrix.

23. The method of claim 18, wherein the step of implanting comprises implanting the device into a portion of the eye.

24. An implantable device for the delivery of at least two bioactive agents to a subject, the device comprising:

a body member comprising

a first set of apertures,

a second set of apertures, and

an inner space comprising

a first bioactive agent and

a second bioactive agent, wherein the first bioactive agent and the second bioactive agent are substantially unmixed in the inner space, and

wherein, during implantation in a subject, the first bioactive agent is releasable from the device through the first set of apertures, and the second bioactive agent is releasable from the device through the second set of apertures.