Compositions of a polyorthoester and an aprotic solvent

• US 9,913,909 B2
• Filed: 09/19/2016
• Issued: 03/13/2018
• Est. Priority Date: 03/15/2013
• Status: Active Grant

• Current Assignee: Heron Therapeutics Inc.
• Original Assignee: Heron Therapeutics Inc.
• Inventors: Ottoboni, Thomas B., Schillinger, Lee Ann Lynn
• Primary Examiner(s): Berrios, Jennifer A
• Application Number:
  US15/269,806
• Publication Number:
  US 20170100483A1
• Time in Patent Office: 540 Days
• Field of Search: None
• CPC Class Codes: A61K 31/439 the ring forming part of a bridged ring system, e.g. quinuclidine 8-azabicyclo [3.2.1] octanes A61K31/46
• CPC Class Codes: A61K 31/445 Non condensed piperidines, e.g. piperocaine
• CPC Class Codes: A61K 31/4458 only substituted in position 2, e.g. methylphenidate
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• 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 47/18 Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
• CPC Class Codes: A61K 47/20 containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
• CPC Class Codes: A61K 47/22 Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
• 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 9/0019 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 9/08 Solutions composition of solutions A61K47/00
• CPC Class Codes: A61P 1/12 Antidiarrhoeals
• CPC Class Codes: A61P 23/02 Local anaesthetics

Abstract

Delivery systems and compositions comprised of a biodegradable polyorthoester polymer, an aprotic solvent, and a drug are described. The solvent is selected to modulate release of drug from the composition, where, in some embodiments, the solvent is rapidly released after administration and provides a corresponding rapid rate of drug release. Alternatively, in other embodiments, the solvent is slowly released from the composition after its administration, and provides a correspondingly slow rate of drug release.

Claims

1. A method of administering a therapeutically active agent to a subject in need thereof, comprising:

dispensing and administering to the subject a delivery system, wherein the delivery system comprises;

a polyorthoester of Formula III;

13. The method of claim 1, wherein the method comprises dispensing the delivery system from a tube.

14. The method of claim 1, wherein the method comprises administering to the subject the delivery system in an amount effective to prevent or reduce pain.

2. A method of treating pain in a subject in need thereof, comprising:

dispensing and administering to the subject a composition comprised of a therapeutically effective amount of a delivery system, wherein the delivery system comprises;

a polyorthoester of Formula III;

3. The method of claim 2, wherein the method reduces or prevents pain in the subject.

4. The method of claim 2, wherein the administering comprises administering the composition locally.

5. The method of claim 4, wherein the administering comprises administering the composition intrathecally, at a nerve, into the epidural space, or to a surgical wound.

6. The method of claim 2, wherein the administering comprises administering the composition regionally.

7. The method of claim 6, wherein the administering comprises administering the composition as a nerve block or as a sensory block.

8. The method of claim 2, wherein the active agent is selected from the group consisting of bupivacaine, ropivacaine, levobupivacaine, dibucaine, mepivacaine, procaine, lidocaine, and tetracaine.

9. The method of claim 2, wherein the therapeutically active agent is bupivacaine.

10. The method of claim 2, wherein the therapeutically active agent is ropivacaine.

11. The method of claim 2, wherein the delivery system has a viscosity of less than about 10,000 cP at 37°

C.

12. The method of claim 2, wherein the aprotic solvent is dimethyl sulfoxide.

15. The method of 1, wherein the aprotic solvent is dimethyl sulfoxide.