Osmotic delivery systems and piston assemblies for use therein

Patent metadata

Field	Value
Publication number	US-10527170-B2
Application number	US-201414316969-A
Country	US
Kind code	B2
Filing date	Jun 27, 2014
Priority date	Aug 9, 2006
Publication date	Jan 7, 2020
Grant date	Jan 7, 2020

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.

First claim

What is claimed is:

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 μg/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 μg/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.

Assignees

• Intarcia Therapeutics Inc

Inventors

• Alessi Thomas R
• Desjardin Michael A
• Lam Stan
• Lautenbach Scott D
• Zamora Pauline C

Classifications

• A61M2005/14513

  with secondary fluid driving or regulating the infusion · CPC title

• A61K9/0004 Primary

  Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas · CPC title

• A61M5/14276

  specially adapted for implantation · CPC title

• A61K9/0024

  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 title

• Y10T29/49826

  Assembling or joining · CPC title