Compositions of a polyorthoester and an aprotic solvent

• US 10,398,686 B2
• Filed: 03/13/2017
• Issued: 09/03/2019
• Est. Priority Date: 03/15/2013
• Status: Active Grant

• Current Assignee: Heron Therapeutics Inc.
• Original Assignee: Heron Therapeutics Inc.
• Inventors: Ottoboni, Thomas B., Girotti, Lee Ann Lynn
• Primary Examiner(s): Bredefeld, Rachel E
• Assistant Examiner(s): Bori, Ibrahim D
• Application Number:
  US15/457,545
• Publication Number:
  US 20170182168A1
• Time in Patent Office: 904 Days
• 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 delivery system, comprising:

a polyorthoester;

dimethyl sulfoxide in which the polyorthoester is miscible to form a single phase; and

bupivacaine dispersed or solubilized in the single phase;

wherein the polyorthoester is a polyorthoester of Formula III;

2. The delivery system of claim 1, wherein bupivacaine is dispersed in the single phase.

3. The delivery system of claim 1, wherein bupivacaine is solubilized in the single phase.

4. The delivery system of claim 1, wherein the delivery system has a viscosity of less than about 10,000 cP at 37°

C.

5. The delivery system of claim 1, where the polyorthoester has a molecular weight between about 1,000 and 10,000 daltons.

6. The delivery system of claim 1, wherein bupivacaine is in an amount of about 1-20 percent by weight of the delivery system.

7. The delivery system of claim 6, wherein bupivacaine is in an amount of about 2-5 percent by weight of the delivery system.

8. The delivery system of claim 1, wherein dimethyl sulfoxide is in an amount of about 10-60 percent by weight of the delivery system.

9. The delivery system of claim 8, wherein dimethyl sulfoxide is in an amount of about 10-20 percent by weight of the delivery system.

10. The delivery system of claim 1, wherein the polyorthoester is in an amount of about 50-80 percent by weight of the delivery system.