Polyoxaester suspending vehicles for use with implantable delivery systems

• US 20060246138A1
• Filed: 03/13/2006
• Published: 11/02/2006
• Est. Priority Date: 03/15/2005
• Status: Active Grant

• Current Assignee: Intarcia Therapeutics, Inc.
• Original Assignee: Intarcia Therapeutics, Inc.
• Inventors: Nathan, Aruna, Rohloff, Catherine Manya, Kang, Ling-Ling, Berry, Stephen Andrew
• Granted Patent: US 7,959,938 B2
• Time in Patent Office: Days
• US Class Current: 424/486
• 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

Abstract

Liquid polyoxaester polymer materials are provided as suspending vehicles suitable for dispensing of pharmaceutically active agents, such as proteins, from delivery devices, for example, pump-driven dosage forms. Polyoxaesters are made from at least one diacid and at least one diol. Through the use of polyoxaesters virtually solvent-free pharmaceutical suspensions can be created.

Claims

1. A pharmaceutical suspension for use in a pump-driven pharmaceutical dosage form comprising a pharmaceutically active agent and a polyoxaester.

2. The suspension of claim 1 which is substantially free of solvents.

3. The suspension of claim 1, wherein the polyoxaester comprises reaction products of at least one diacid and at least one diol.

4. The suspension of claim 2, wherein the diacid is a polyglycolic diacid, a 3,6-trioxaundecanedioic diacid, a 3,6,9-trioxaundecanedioic diacid, or combinations thereof.

5. The suspension of claim 2, wherein the diol is an ethyleneglycol, a propanediol, a butanediol, a pentanediol, cyclopentanediol, a hexanediol, a cyclohexanediol, an octanediol, a decanediol, a dodecanediol, cyclohexanedimethanol, polyethyleneglycol, polypropyleneglycol, or combinations thereof.

6. The suspension of claim 1, wherein the polyoxaester comprises condensation products of a mixture comprising a polyglycolic diacid and an ethyleneglycol.

7. The suspension of claim 6 wherein the mixture further comprises a 3,6,9-trioxaundecanedioic diacid.

8. The suspension of claim 6 wherein a molecular weight of the polyoxaester is from approximately 1,000 to approximately 100,000.

9. The suspension of claim 1, wherein the polyoxaester comprises condensation products of a mixture comprising a 3,6,9-trioxaundecanedioic diacid and an ethyleneglycol.

10. The suspension of claim 9, wherein a molecular weight of the polyoxaester is from approximately 1,000 to approximately 100,000.

11. The suspension of claim 1 wherein the pharmaceutically active agent comprises a protein, peptide, small molecule, or combinations thereof.

12. The suspension of claim 1 wherein the pharmaceutically active agent comprises lysozyme, interferon, erythropoietin, granulocyte macrophage colony stimulating factor (GM-CSF), human growth hormone releasing hormone (huGHRH), insulin, desmopressin, infliximab, an antibody, an agent conjugated to a targeting ligand, bone morphogenic proteins, Nesiritide, alpha-interferon, beta-interferon, omega-interferon, adrenocorticotropic hormone, angiotensin I, angiotensin II, atrial natriuretic peptide, bombesin, bradykinin, calcitonin, cerebellin, dynorphin N, alpha endorphin, beta endorphin, endothelin, enkephalin, epidermal growth factor, fertirelin, follicular gonadotropin releasing peptide, galanin, glucagon, glucagon-like peptide-1 (GLP-1), gonadorelin, gonadotropin, goserelin, growth hormone releasing peptide, histrelin, human growth hormone, insulin, leuprolide, LHRH, motilin, nafarerlin, neurotensin, oxytocin, relaxin, somatostatin, substance P, tumor necrosis factor, triptorelin, vasopressin, nerve growth factor, blood clotting factors, ribozymes, antisense oligonucleotide, or combinations thereof.

13. The suspension of claim 1 wherein the pharmaceutically active agent comprises risperidone, paliperidone, ocaperidone, or combinations thereof.

14. A dosage form comprising:

a first wall that maintains its physical and chemical integrity during the life of the dosage form and is substantially impermeable to a pharmaceutical suspension;

a second wall that is partially permeable to an exterior fluid;

a compartment defined by the first wall and the second wall;

a pharmaceutical suspension that is positioned within the compartment and comprises a pharmaceutically active agent and a polyoxaester;

a pump in communication with the first wall, the second wall, and the compartment; and

an exit port in communication with the compartment.

15. The dosage form of claim 14 wherein the pump comprises an osmotic pump.

16. The dosage form of claim 14 wherein upon contact with an aqueous medium, the pharmaceutical suspension is flowable through the exit port under a force exerted by the pump under normal operating conditions.

17. The dosage form of claim 14 wherein the pharmaceutical suspension is substantially homogeneous for at least 3 months at 37°

C.

18. A method comprising administering the dosage form of claim 14 to a mammal.

19. A method of making the dosage form of claim 14.

20. A kit comprising a dosage form of claim 14 and instructions for administering the dosage form.