Sustained delivery of an active agent using an implantable system

• US 5,985,305 A
• Filed: 10/02/1997
• Issued: 11/16/1999
• Est. Priority Date: 02/02/1996
• Status: Expired due to Term

• Current Assignee: Intarcia Therapeutics, Inc.
• Original Assignee: ALZA Corporation (Johnson & Johnson)
• Inventors: Lautenbach, Scott D., Landrau, Felix A., Magruder, Judy A., Eckenhoff, James B., Wright, Jeremy C., Peery, John R., Dionne, Keith E.
• Primary Examiner(s): BROUILLETTE, D GABRIELLE
• Application Number:
  US08/943,007
• Time in Patent Office: 775 Days
• Field of Search: 424/473, 424/422, 424/424, 604/891.1
• US Class Current: 424/422
• CPC Class Codes: A61K 38/09 Luteinising hormone-releasing hormone [LHRH] , i.e. Gonadotropin-releasing hormone [GnRH]; Related peptides
• CPC Class Codes: A61K 9/0004 Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas
• 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: A61M 2005/14513 with secondary fluid driving or regulating the infusion
• CPC Class Codes: A61M 2206/10 Flow characteristics
• CPC Class Codes: A61M 5/14526 the piston being actuated by fluid pressure

Abstract

The invention is directed to a device for delivering an active agent formulation for a predetermined administration period. An impermeable reservoir is divided into a water-swellable agent chamber and an active agent formulation chamber. Fluid from the environment is imbibed through a semipermeable plug into the water-swellable agent chamber and the active agent formulation is released through a back-diffusion regulating outlet. Delivery periods of up to 2 years are achieved.

Claims

1. An implantable device for delivering an active agent to a fluid environment of use, said device comprising a reservoir and a back-diffusion regulating outlet in mating relationship, wherein a flow path for the active agent comprises a pathway formed between the mating surfaces of the reservoir and the back-diffusion regulating outlet.

2. The device of claim 1 where the active agent is delivered at a rate of 0.02 to 50 μ

l/day.

3. The device of claim 1 wherein the active agent is selected from the group consisting of a protein, a peptide or a gene therapy agent.

4. The device of claim 3 wherein the active agent is leuprolide.

5. The device of claim 1 wherein the active agent is delivered to a site remote from the device.

6. An implantable fluid-imbibing active agent delivery system comprising an impermeable reservoir and containing a piston that divides the reservoir into an active agent containing chamber and a water-swellable agent containing chamber, wherein the active agent containing chamber is provided with a back-diffusion regulating outlet and the water-swellable agent containing chamber is provided with a semipermeable plug;

wherein the plug is releasable from the reservoir at an internal pressure that is lower than the maximum osmotic pressure generated by the water-swellable agent.

7. An implantable fluid-imbibing active agent delivery system comprising an impermeable reservoir and containing a piston that divides the reservoir into an active agent containing chamber and a water-swellable agent containing chamber, wherein the active agent containing chamber is provided with a back-diffusion regulating outlet and the water-swellable agent containing chamber is provided with a semipermeable plug;

wherein the outlet is releasable from the reservoir at an internal pressure that is lower than the maximum osmotic pressure generated by the water-swellable agent.

8. An implantable active agent delivery system for delivering an active agent to a fluid environment of use, said agent being susceptible to degradation if exposed to the fluid environment of use prior to delivery, said system comprising:

(a) a piston that divides the system into a first and second chamber, the first and second chambers each having an open end;

(b) a water-swellable agent formulation in the first chamber;

(c) an active agent formulation in the second chamber;

(d) a semipermeable plug in the open end of the first chamber; and

(e) a back-diffusion regulating outlet in the open end of the second chamber;

wherein said system effectively seals the active agent chamber and isolates it from the environment of use.

9. The system of claim 8 wherein the active agent is selected from the group consisting of a protein, a peptide or a gene therapy agent.

10. The system of claim 8 wherein the active agent is leuprolide.

11. A back-diffusion regulating outlet useful in an active agent delivery system for delivering active agent to a fluid environment of use, said outlet defining a flow path wherein the length, interior cross-sectional shape and area provide for an average linear velocity of the active agent that is higher than the linear inward flux of the fluid environment of use.

12. The outlet of claim 11 wherein the flow path is helical in shape.