Compositions of a polyorthoester and an aprotic solvent

Patent metadata

Field	Value
Publication number	US-12318376-B2
Application number	US-202217572493-A
Country	US
Kind code	B2
Filing date	Jan 10, 2022
Priority date	Mar 15, 2013
Publication date	Jun 3, 2025
Grant date	Jun 3, 2025

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 delivery system, comprising:
a polyorthoester;
an aprotic solvent in which the polyorthoester is miscible to form a single phase; and
a local amide- or anilide-type anesthetic dispersed or solubilized in the single phase;
wherein the polyorthoester is represented by the structure shown as 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 0 to 10;
R 5 is H or methyl, and
the fraction of A units that are of the formula R 1 is between 0 and 25 mole percent
wherein the anesthetic is released from the system over a period of between approximately 1 day and approximately 8 weeks.

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

3. The delivery system of claim 1 , wherein the anesthetic 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 , wherein the aprotic solvent is an amide or a sulfoxide.

6. The delivery system of claim 5 , wherein the aprotic solvent is an amide selected from the group consisting of 2-pyrrolidone, dimethyl formamide, N-methyl-2-pyrrolidone, N-ethyl-2-pyrrolidone, dimethyl acetamide, N-cyclohexyl-2-pyrrolidone and caprolactam.

7. The delivery system of claim 5 , wherein the aprotic solvent is a sulfoxide selected from either dimethyl sulfoxide or decylmethylsulfoxide.

8. The delivery system of claim 1 , wherein the aprotic solvent is selected from dimethylsulfoxide, dimethyl acetamide, and N-methyl pyrrolidone.

9. The delivery system of claim 1 , wherein local amide- or anilide-type anesthetic is selected from the group consisting of bupivacaine, levobupivacaine, dibucaine, mepivacaine, procaine, lidocaine, tetracaine, and ropivacaine.

10. The delivery system of claim 9 , wherein the local amide- or anilide type anesthetic is bupivacaine.

11. The delivery system of claim 9 , wherein the local amide- or anilide type anesthetic is ropivacaine.

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

13. The delivery system of claim 1 , wherein the aprotic solvent is in an amount between 15-50 percent by weight of the delivery system; and the local amide- or anilide-type anesthetic is in an amount between 3 and 30 percent by weight of the delivery system.

14. A method of administering a local amide- or anilide-type anesthetic, comprising dispensing from a needle the delivery system of claim 1 .

15. The method of claim 14 , comprising dispensing from a needle a delivery system of claim 8 .

16. A method of providing local anesthesia to a patient, comprising administering to a patient the delivery system of claim 1 in an amount effective for reducing or preventing pain.

17. The method of claim 16 , wherein the administering comprises dispensing the delivery system from a needle.

18. The method of claim 16 , wherein the administering comprises injecting the delivery system in a region of tissue near a nerve, into an epidural space, as an intrathecal injection, around the periphery of a surgical site or wound or dispensing directly into a surgical site or wound.

19. The method of claim 16 , comprising administering to the patient the delivery system of claim 8 .

Assignees

• Heron Therapeutics Inc

Inventors

• Ottoboni Thomas B
• Girotti Lee Ann Lynn

Classifications

• A61K47/10

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

• A61K9/08

  Solutions {(composition of solutions A61K47/00)} · CPC title

• A61K9/0019

  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 title

• A61K47/18

  Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids · CPC title

• A61K47/14

  Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters · CPC title