Short duration depot formulations

• US 10,201,496 B2
• Filed: 09/15/2016
• Issued: 02/12/2019
• Est. Priority Date: 06/25/2002
• Status: Active Grant

• Current Assignee: DURECT Corporation
• Original Assignee: DURECT Corporation
• Inventors: Chen, Guohua, Priebe, David T.
• Primary Examiner(s): Vu, Jake M
• Application Number:
  US15/267,070
• Publication Number:
  US 20170087086A1
• Time in Patent Office: 880 Days
• Field of Search: None
• CPC Class Codes: A61K 31/445 Non condensed piperidines, e.g. piperocaine
• CPC Class Codes: A61K 38/27 Growth hormone [GH], i.e. somatotropin
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/14 Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
• CPC Class Codes: A61K 47/34 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers A61K47/10 takes precedence
• CPC Class Codes: A61K 9/0014 Skin, i.e. galenical aspects of topical compositions non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• 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 9/06 Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels composition of ointments, creams or gels A61K47/00
• CPC Class Codes: A61P 23/00 Anaesthetics
• CPC Class Codes: A61P 23/02 Local anaesthetics

Abstract

Methods and compositions for systemically or locally administering by implantation a beneficial agent to a subject are described, and include, for example, depot gel compositions that can be injected into a desired location and which can provide controlled release of a beneficial agent over a short duration of time. The compositions include a low molecular weight biocompatible polymer, a biocompatible solvent having low water miscibility that forms a viscous gel with the polymer and limits water uptake by the implant, and a beneficial agent.

Claims

1. A composition comprising:

(a) a polyorthoester having a weight average molecular weight ranging from about 3000 to about 10,000;

(b); and

(c) bupivacaine base or pharmaceutically acceptable salt thereof in an amount ranging from about 1 wt % to about 20 wt % of the composition,

wherein the ratio of polyorthoester to triacetin ranges from about 40;

60 to about 75;

25.

2. The composition of claim 1, wherein the bupivacaine base or pharmaceutically acceptable salt thereof comprises bupivacaine base.

3. The composition of claim 1, wherein the polyorthoester has a weight average molecular weight ranging from about 4000 to about 8000.

4. The composition of claim 2, wherein the polyorthoester has a weight average molecular weight ranging from about 4000 to about 8000.

5. The composition of claim 1, wherein the bupivacaine base or pharmaceutically acceptable salt thereof is present in an amount ranging from about 2 wt % to about 20 wt % of the composition.

6. The composition of claim 2, wherein the bupivacaine base or pharmaceutically acceptable salt thereof is present in an amount ranging from about 2 wt % to about 20 wt % of the composition.

7. The composition of claim 3, wherein the bupivacaine base or pharmaceutically acceptable salt thereof is present in an amount ranging from about 2 wt % to about 20 wt % of the composition.

8. The composition of claim 4, wherein the bupivacaine base or pharmaceutically acceptable salt thereof is present in an amount ranging from about 2 wt % to about 20 wt % of the composition.

9. The composition of claim 1, wherein the ratio of polyorthoester to triacetin ranges from about 50:

50 to about 75;

25.

10. The composition of claim 2, wherein the ratio of polyorthoester to triacetin ranges from about 50:

50 to about 75;

25.

11. The composition of claim 3, wherein the ratio of polyorthoester to triacetin ranges from about 50:

50 to about 75;

25.

12. The composition of claim 4, wherein the ratio of polyorthoester to triacetin ranges from about 50:

50 to about 75;

25.

13. The composition of claim 5, wherein the ratio of polyorthoester to triacetin ranges from about 50:

50 to about 75;

25.

14. The composition of claim 6, wherein the ratio of polyorthoester to triacetin ranges from about 50:

50 to about 75;

25.

15. The composition of claim 7, wherein the ratio of polyorthoester to triacetin ranges from about 50:

50 to about 75;

25.

16. The composition of claim 8, wherein the ratio of polyorthoester to triacetin ranges from about 50:

50 to about 75;

25.