Opioid independent surgical anesthetic

Patent metadata

Field	Value
Publication number	US-12414917-B2
Application number	US-202217683687-A
Country	US
Kind code	B2
Filing date	Mar 1, 2022
Priority date	Sep 13, 2019
Publication date	Sep 16, 2025
Grant date	Sep 16, 2025

Abstract

An opioid independent surgical anesthetic composition includes an injectable dosage form of a hydrogel having a plurality of solid lipid matrix particles entrapped therein. The solid lipid matrix particles include a lipophilic local anesthetic drug and a lipid glyceride (e.g., saturated triglyceride or lipid blend of various lipid glycerides). Methods for creating a long-acting local anesthetic product can include creating a bulk solid of a lipid matrix product by heating a lipid solvent above its melting point, dissolving a lipophilic local anesthetic drug therein, reducing a temperature of the resultant drug-lipid solution to below the melting point of the lipid solvent, and heat annealing the lipid matrix to remove or reduce presence of any unstable polymorphs in the lipid matrix. The methods can further include crushing the bulk solid of the lipid matrix product to form solid lipid matrix particles and entrapping the solid lipid matrix particles within a hydrogel.

First claim

What is claimed is:

1. An opioid independent surgical anesthetic composition, comprising an injectable dosage form of a gel having a plurality of solid lipid matrix particles entrapped therein, the plurality of solid lipid matrix particles comprising a lipophilic local anesthetic drug and a saturated glyceride, wherein the injectable dosage form is shear thinning and is injectable through an 18 to 25 gauge needle, wherein the injectable dosage reforms into a stable gel after passing through the 18 to 25 gauge needle, and wherein the composition is biphasic so as to release the local anesthetic drug in a biphasic manner when administered at a surgical site, the biphasic release comprising an initial burst phase followed by a sustained release phase.

2. The composition of claim 1 , wherein the saturated glyceride comprises a lipid blend including one or more of a monoglyceride, a diglyceride, or a triglyceride.

3. The composition of claim 1 , wherein the saturated glyceride comprises a saturated triglyceride.

4. The composition of claim 1 , wherein the gel comprises a hyaluronic acid hydrogel.

5. The composition of claim 4 , wherein the hyaluronic acid is included in an amount from 0.5% to 3% by weight.

6. The composition of claim 4 , wherein the hyaluronic acid has a molecular weight in a range from 500,000 to 3,000,000 Da.

7. The composition of claim 1 , wherein the lipophilic local anesthetic drug comprises at least one amide based anesthetic.

8. The composition of claim 1 , wherein the plurality of solid lipid matrix particles substantially comprises triglycerides forming a β-phase crystalline state.

9. The composition of claim 1 , wherein the solid lipid matrix particles have a melting point greater than about 45° C.

10. The composition of claim 1 , wherein the solid lipid matrix particles are comprised of one or more of monoglycerides, diglycerides, or triglycerides with carbon chain lengths of 12 to 22 carbon atoms.

11. The composition of claim 1 , wherein each of the plurality of solid lipid matrix particles has a longest dimension of about 200 μm or less.

12. The composition of claim 1 , wherein the local anesthetic drug has a concentration relative to the solid matrix lipid particle of from 1% to 50% by weight.

13. The composition of claim 1 , wherein the local anesthetic drug has a concentration relative to the composition as a whole that is from 0.5% to 10% by weight.

14. The composition of claim 1 , wherein the solid lipid matrix particles have a density within the composition as a whole that is from 25 mg/mL to 300 mg/mL.

15. An opioid independent surgical anesthetic composition as recited in claim 1 , wherein the composition consists essentially of the injectable dosage form that is ready-to-use, the composition being a hyaluronic acid hydrogel having a liposomal emulsion containing bupivacaine, ropivacaine, lidocaine, or another amide based local anesthetic entrained therein.

16. The composition of claim 15 , wherein the biphasic composition releases bupivacaine, ropivacaine, lidocaine, or another amide based local anesthetic in a biphasic manner when administered at a surgical site, the biphasic release comprising a burst phase and a sustained release phase, wherein:
(i) between 30%-70% of the bupivacaine, ropivacaine, lidocaine, or another amide based local anesthetic is cumulatively released from the hydrogel during the burst phase between 8-24 hours post administration, and/or
(ii) between 70%-99% of the bupivacaine, ropivacaine, lidocaine, or another amide based local anesthetic is cumulatively released from the hydrogel by 72 hours post administration.

17. The composition of claim 1 , wherein the solid lipid matrix particles have a melting point greater than about 70° C.

18. The composition of claim 1 , wherein the solid lipid matrix particles consist essentially of bupivacaine in tristearin.

19. The composition of claim 1 , wherein the solid lipid matrix particles consist of bupivacaine in tristearin.

20. An opioid independent surgical anesthetic composition packaged within a syringe, the composition comprising an injectable dosage form of a gel having a plurality of solid lipid matrix particles entrapped therein, the plurality of solid lipid matrix particles comprising a lipophilic local anesthetic drug comprising bupivacaine, in tristearin as the solid lipid matrix, wherein the injectable dosage form is shear thinning and is injectable through an 18 to 25 gauge needle attached to the syringe, and wherein the injectable dosage reforms into a stable gel after passing through the 18 to 25 gauge needle;
wherein the composition consists essentially of the injectable dosage form that is ready-to-use provided within the syringe with an attached 18 to 25 gauge needle;
wherein the composition is biphasic so as to release the bupivacaine in a biphasic manner when administered at a surgical site, the biphasic release comprising an initial burst phase and a sustained release phase, wherein:
(i) between 30%-70% of the bupivacaine is cumulatively released from the gel during the burst phase between 8-24 hours post administration; and
(ii) between 70%-99% of the bupivacaine is cumulatively released from the gel by 72 hours post administration.

21. The composition packaged within a syringe of claim 20 , wherein the bupivacaine has a concentration relative to the solid matrix lipid particle of from 1% to 50% by weight.

22. An opioid independent surgical anesthetic composition, comprising an injectable dosage form of a gel having a plurality of solid lipid matrix particles entrapped therein, the plurality of solid lipid matrix particles consisting of an oil and bupivacaine in tristearin, wherein the injectable dosage form is shear thinning to facilitate injection through an 18 to 25 gauge needle and wherein the composition is configured to release the bupivacaine in a biphasic manner when administered at a surgical site, the biphasic release comprising an initial burst phase followed by a sustained release phase.

23. An opioid independent surgical anesthetic composition, comprising an injectable dosage form of a gel having a plurality of lipid matrix particles disposed therein, the plurality of lipid matrix particles consisting of a lipophilic local anesthetic drug, an oil, and a saturated triglyceride, wherein the injectable dosage form is shear thinning and is injectable through an 18 to 25 gauge needle and wherein the composition is biphasic so as to release the local anesthetic drug in a biphasic manner when administered at a surgical site, the biphasic release comprising an initial burst phase followed by a sustained release phase.

Assignees

• Univ Utah Res Found

Inventors

• Davis Brett
• Simpson Andrew M
• Agarwal Jayant P
• Shea Jill E
• Sant Himanshu Jayant
• Gale Bruce K

Classifications

• A61K31/445 Primary

  Non condensed piperidines, e.g. piperocaine · 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

• A61K9/1277

  Preparation processes; Proliposomes · CPC title

• A61K47/36

  Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin · CPC title

• A61K9/5123

  Organic compounds, e.g. fats, sugars · CPC title