Osmotic delivery systems and piston assemblies for use therein

• US 10,527,170 B2
• Filed: 06/27/2014
• Issued: 01/07/2020
• Est. Priority Date: 08/09/2006
• Status: Active Grant

• Current Assignee: Intarcia Therapeutics, Inc.
• Original Assignee: Intarcia Therapeutics, Inc.
• Inventors: Alessi, Thomas R., DesJardin, Michael A., Lam, Stan, Lautenbach, Scott D., Zamora, Pauline C.
• Primary Examiner(s): Vu, Quynh-Nhu H.
• Application Number:
  US14/316,969
• Publication Number:
  US 20140378900A1
• Time in Patent Office: 2,020 Days
• 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 2205/0216 Materials providing elastic properties, e.g. for facilitating deformation and avoid breaking
• CPC Class Codes: A61M 5/14276 specially adapted for implantation
• CPC Class Codes: A61M 5/14526 the piston being actuated by fluid pressure
• CPC Class Codes: F16J 9/26 characterised by the use of particular materials
• CPC Class Codes: F16J 9/28 of non-metals
• CPC Class Codes: Y10T 29/49826 Assembling or joining

Abstract

An osmotic delivery system is disclosed for delivering an active agent formulation to a fluid environment. The osmotic delivery system typically comprises a reservoir having a lumen that contains the active agent formulation and an osmotic agent formulation and a piston assembly positioned in the lumen to isolate the active agent formulation from the osmotic agent formulation. The piston assembly typically comprises a body constructed and arranged for positioning in the lumen. The body is typically made of a polymeric material that is, for example, resistant to leaching in an organic solvent. In one embodiment, the body is a columnar body having a rim at a distal end thereof for engaging and sealing against a wall of the reservoir and the piston assembly further comprises a spring retained at the distal end of the columnar body for biasing the rim of the columnar body against the wall of the reservoir.

Claims

1. A method of treating diabetes in a subject in need of such treatment, comprising administering an osmotic delivery system loaded with a suspension formulation comprising an active agent to the subject, wherein the osmotic delivery system comprises:

a reservoir comprising an interior wall defining a lumen that contains the suspension formulation and an osmotic agent formulation;

a piston assembly positioned in the lumen to isolate the suspension formulation from the osmotic agent formulation, wherein the piston assembly comprises;

a columnar body that has a core made of a polymeric material comprising an ultra-high molecular weight polyethylene,

a rim at a distal end thereof for engaging and sealing against the interior wall of the reservoir, and

a spring retained at the distal end for biasing the rim against the wall of the reservoir;

the suspension formulation comprises a suspension vehicle comprising one or more organic solvents selected from the group consisting of benzyl benzoate and benzyl alcohol;

the suspension formulation comprises less than 9.0 μ

g/mL of non-volatile leachates produced by the piston assembly and resulting from an interaction between the suspension formulation and the piston assembly; and

the active agent is exendin-4.

2. The method of claim 1, wherein the spring is retained in a cavity at the distal end of the columnar body.

3. The method of claim 1, wherein the spring is made of a non-reactive metal.

4. The method of claim 1, the osmotic delivery system further comprising a semipermeable membrane positioned at a first end of the reservoir adjacent the osmotic agent formulation.

5. The method of claim 4, the osmotic delivery system further comprising a flow modulator positioned at a second end of the reservoir adjacent the suspension formulation, said flow modulator having an orifice for delivering the suspension formulation to the fluid environment.

6. The method of claim 1, wherein the piston assembly is movable within the reservoir in response to pressure within the reservoir.

7. The method of claim 1, wherein the reservoir is made of an impermeable material.

8. The method of claim 1, wherein the suspension formulation comprises a particle formulation of the active agent.

9. The method of claim 1, wherein:

the reservoir is made of a titanium alloy;

the suspension formulation comprises

a particle formulation of the active agent, the particle formulation comprising exendin-4 and further comprising sucrose, methionine, citric acid monohydrate, and sodium citrate, and

the suspension vehicle comprising benzyl benzoate and further comprising polyvinylpyrrolidone;

the osmotic agent formulation comprises two cylindrical tablets, each tablet comprising sodium chloride salt with cellulosic and povidone binders;

the spring retained at the distal end for biasing the rim against the wall of the reservoir is a canted coil spring;

the osmotic delivery system further comprising;

a semipermeable membrane positioned at a first distal end of the reservoir adjacent the osmotic agent formulation, wherein the semipermeable membrane comprises polyurethane; and

a flow modulator positioned at a second distal end of the reservoir adjacent the suspension formulation, wherein the flow modulator comprises polyetheretherketone.

10. The method of claim 1, wherein the suspension formulation comprises less than 1.4 μ

g/mL of volatile leachates produced by the piston assembly and resulting from an interaction between the suspension formulation and the piston assembly.

11. The method of claim 1, wherein the suspension vehicle comprises benzyl benzoate.

12. The method of claim 1, wherein the suspension vehicle comprises benzyl alcohol.