Compositions of a polyorthoester and an aprotic solvent

Patent metadata

Field	Value
Publication number	US-9913909-B2
Application number	US-201615269806-A
Country	US
Kind code	B2
Filing date	Sep 19, 2016
Priority date	Mar 15, 2013
Publication date	Mar 13, 2018
Grant date	Mar 13, 2018

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.

First claim

What is claimed is:

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;

where
A is R 1 or R 3 ,
R* is C1-4 alkyl,
n ranges from 5 to 1000,
R 1 is:

p and q are integers that vary from between about 1 to 20 and the average number of p or the average of the sum of p and q is between 1 and 7;
R 3 and R 6 are each independently:

x is an integer of 1-4;
R 5 is H or methyl, and
the fraction of A units that are of formula R 1 is between 10-25 mole percent;

an aprotic solvent in which the polyorthoester is miscible to form a single phase, wherein the aprotic solvent is selected from dimethyl sulfoxide, dimethyl acetamide, and N-methyl pyrrolidone; and
a local amide- or anilide-type anesthetic dispersed or solubilized in the single phase,
wherein the aprotic solvent is present in amounts ranging from about 10-25% by weight of the delivery system and the polyorthoester of formula III is present in amounts ranging from about 45-80% by weight of the delivery system.

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;

where
A is R 1 or R 3 ,
R* is C1-4 alkyl,
n ranges from 5 to 1000,
R 1 is:

p and q are integers that vary from between about 1 to 20 and the average number of p or the average of the sum of p and q is between 1 and 7;
R 3 and R 6 are each independently:

x is an integer of 1-4;
R 5 is H or methyl, and
the fraction of A units that are of formula R 1 is between 10-25 mole percent;

an aprotic solvent in which the polyorthoester is miscible to form a single phase, wherein the aprotic solvent is selected from dimethyl sulfoxide, dimethyl acetamide, and N-methyl pyrrolidone; and
a local amide- or anilide-type anesthetic dispersed or solubilized in the single phase.

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.

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.

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

Assignees

• Heron Therapeutics Inc

Inventors

• Ottoboni Thomas B
• Schillinger Lee Ann Lynn

Classifications

• A61P23/02

  Local anaesthetics · CPC title

• A61P1/12

  Antidiarrhoeals · CPC title

• A61K31/485

  Morphinan derivatives, e.g. morphine, codeine · CPC title

• A61K47/34 Primary

  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 title

• A61K47/10

  Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers · CPC title