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EP-4110293-B1 - EUTECTIC BASED ANESTHETIC COMPOSITIONS AND APPLICATIONS THEREOF

EP4110293B1EP 4110293 B1EP4110293 B1EP 4110293B1EP-4110293-B1

Inventors

  • JAY, MICHAEL
  • ZELDES, Ben
  • MARTIN, Jesse
  • MCMILLAN, STEPHEN

Dates

Publication Date
20260506
Application Date
20210224

Claims (13)

  1. An anesthetic emulsion comprising: a dispersed phase comprising a eutectic mixture consisting of lidocaine and benzocaine; and an aqueous or aqueous-based continuous phase comprising bupivacaine.
  2. The anesthetic emulsion of claim 1, wherein a weight ratio of lidocaine to benzocaine ranges from 1.5 to 3.
  3. The anesthetic emulsion of claim 1, wherein the aqueous phase further comprises one or more gelling agents, preferably wherein the one or more gelling agents are present in a total amount of 15-25 weight percent of the anesthetic emulsion, more preferably wherein the one or more gelling agents comprises a block copolymer comprising hydrophobic and hydrophilic blocks.
  4. The anesthetic emulsion of claim 1, wherein the lidocaine is present in an amount of 10-20 weight percent of the anesthetic emulsion.
  5. The anesthetic emulsion of claim 1, wherein the benzocaine is present in an amount of 3-8 weight percent of the anesthetic emulsion.
  6. The anesthetic emulsion of claim 1 having a viscosity of 3-5 Pa-s at 30°C and a shear rate of 500/s.
  7. The anesthetic emulsion of claim 1, wherein the bupivacaine is present in an amount up to 5 weight percent of the anesthetic emulsion.
  8. An anesthetic emulsion for use in a method of treating pain from a site of damaged tissue comprising: applying said anesthetic emulsion to the site of damaged tissue, the anesthetic emulsion comprising a dispersed phase comprising a eutectic mixture consisting of lidocaine and benzocaine, and an aqueous or aqueous-based continuous phase comprising bupivacaine.
  9. The anesthetic emulsion for use according to claim 8 further comprising releasing at least one of the lidocaine, benzocaine, and bupivacaine to the site of damaged tissue over a period of at least three days.
  10. The anesthetic emulsion for use according to claim 8, wherein the site of damaged tissue is a surgical site, preferably, wherein the surgical site resides in a patient's mouth more preferably wherein the surgical site is a tooth socket.
  11. The anesthetic emulsion for use according to claim 8, wherein the site of damaged tissue is a site of injury, preferably wherein the site of injury comprises one or more lacerations.
  12. The anesthetic emulsion for use according to claim 8, wherein the aqueous phase further comprises one or more gelling agents.
  13. The anesthetic emulsion for use according to claim 8, wherein the anesthetic emulsion has a viscosity of 3-5 Pa-s at 30°C and a shear rate of 500/s.

Description

FIELD The present disclosure relates to anesthetic compositions and, in particular, to non-opiate anesthetic emulsions comprising eutectic mixtures. BACKGROUND A need exists for an intermediate-length pain management option for dealing with dental and/or other surgical pain. Topical and injected local anesthetics are highly effective at managing pain during and shortly after procedures, and in most cases subsequent pain is mild. However, tooth extractions can result in prolonged pain, particularly in cases of "dry-socket" - intense, sometimes radiating pain caused by loss of the blood clot from the alveolar (tooth) socket. Dry-socket pain presents one to three days after extraction, can last up to 10 days, and occurs in a significant number of third-molar (wisdom tooth) extractions, although any tooth extraction carries some risk. Currently, opioids are frequently prescribed following third-molar tooth extractions as a post-operative care strategy to manage acute pain. Furthermore, since third molars are typically removed in adolescence or young adulthood, this is the first exposure to opioids for many patients, and results in an increased risk for persistent opioid use and abuse. The Centers for Disease Control and Prevention (CDC) reported that in 2018, 67,367 drug overdose deaths occurred in the United States, mostly (70%) driven by synthetic opioids. Dental practitioners are among the leading prescribers of opioid prescriptions, with 85% of oral surgeons indicating they nearly always prescribe opiates after third molar extraction to reduce acute pain. Approximately 21 million surgical tooth extractions are performed on 10 million patients each year in the U.S. (Survey of Dental Services Rendered, American Dental Association). US 2017/319534 A1 discloses an eutectic anesthetic composition comprising: at least one adjuvant anesthetic; at least one polar oil having a droplet diameter in the range of about 10 microns to about 100 microns and having a Hydrophile-Lipophile Balance (HLB) number above about 11.0; at least one lipophilic emulsifier having a HLB number above 11.0; at least one penetrating agent comprising phosphatidylcholine; and at least one thermo gelling agent with long-chain, straight or branched polymers, wherein the adjuvant anesthetic may be selected from the group consisting of benzocaine, bupivacaine, dibucaine, diphenhydramine, etidocaine, gabapentin, lidocaine, mepivacaine, nifedipine, pregabalin, prilocaine, procaine, ropivacaine, tetracaine, verapamil, and mixtures thereof. US2020/030305 A1 discloses an acidic emulsion composition comprising a local anesthetic and a glyceride in which a fatty acid(s) having 6 to 12 carbon atoms is/are bound to glycerin via an ester bond(s). SUMMARY The invention is set out in independent claims 1 and 8. Preferred embodiments are reflected in the dependent claims. In view of the serious health and addiction risks associated with opiates, anesthetic emulsions are described herein comprising eutectic mixtures. In some embodiments, the anesthetic emulsions release one or more local anesthetics over a period of several days for continuous pain relief. An anesthetic emulsion according to the present invention comprises a dispersed phase comprising a eutectic mixture consisting of lidocaine and benzocaine, and an aqueous or aqueous-based continuous phase comprising bupivacaine. A ratio of lidocaine to benzocaine, in some embodiments, ranges from 1.5 to 3. Moreover, in some embodiments, lidocaine can be present in an amount of 10-20 weight percent of the anesthetic emulsion, while benzocaine can be present in an amount of 3-8 weight percent of the anesthetic emulsion. Moreover, in some embodiments, bupivacaine is present in an amount up to 5 weight percent of the anesthetic emulsion. Bupivacaine, for example, can be present in an amount of 0.5-3.0 weight percent, in some embodiments. It is described herein that the eutectic mixture further comprises menthol. Menthol can be present in any desired amount consistent with the technical objectives described herein. Menthol, for example, can be present in an amount of 0.5 to 2 weight percent of the anesthetic emulsion. The aqueous or aqueous-based continuous phase may further comprise one or more gelling agents. In some embodiments, one or more gelling agents are present in a total amount of 15-25 weight percent of the anesthetic emulsion. Gelling agents can comprise block copolymers comprising hydrophobic and hydrophilic blocks, in some embodiments. Gelling agents can be employed to adjust viscosity of the anesthetic emulsion. The anesthetic emulsion, for example, can have a viscosity of 3-5 Pa-s at 30°C at a shear rate of 500/s. In another aspect, an anesthetic emulsion for use in a method of treating sites of damaged tissue are described herein. The anesthetic emulsion for use comprises applying an anesthetic emulsion to the site of damaged tissue, the anesthetic emulsion comprising a dispersed phase comprising