Hyaluronic acid-based gels including lidocaine

• US 10,485,896 B2
• Filed: 11/09/2018
• Issued: 11/26/2019
• Est. Priority Date: 08/04/2008
• Status: Active Grant

• Current Assignee: Allergan Industrie SAS (Abbvie Incorporated)
• Original Assignee: Allergan Industrie SAS (Abbvie Incorporated)
• Inventors: Lebreton, Pierre F.
• Primary Examiner(s): Soroush, Ali
• Application Number:
  US16/186,448
• Publication Number:
  US 20190076579A1
• Time in Patent Office: 382 Days
• CPC Class Codes: A61K 2800/91 Injection
• CPC Class Codes: A61K 31/167 having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
• CPC Class Codes: A61K 31/728 Hyaluronic acid
• CPC Class Codes: A61K 47/36 Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
• CPC Class Codes: A61K 8/0241 Containing particulates characterized by their shape and/or structure see also A61K8/04, A61K8/11, and A61K8/14, further aspects are classified in A61K2800/40 and subcodes
• CPC Class Codes: A61K 8/375 the alcohol moiety containing more than one hydroxy group
• CPC Class Codes: A61K 8/42 Amides
• CPC Class Codes: A61K 8/735 Mucopolysaccharides, e.g. hyaluronic acid; Derivatives thereof
• 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 9/0021 Intradermal administration, e.g. through microneedle arrays, needleless injectors mechanical aspects A61M
• 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 9/06 Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels composition of ointments, creams or gels A61K47/00
• CPC Class Codes: A61L 2/0023 Heat
• CPC Class Codes: A61L 2/0029 Radiation
• CPC Class Codes: A61L 2300/402 Anaestetics, analgesics, e.g. lidocaine
• CPC Class Codes: A61L 2300/602 Type of release, e.g. controlled, sustained, slow
• CPC Class Codes: A61L 2400/06 Flowable or injectable implant compositions
• CPC Class Codes: A61L 2430/34 for soft tissue reconstruction
• CPC Class Codes: A61L 27/20 Polysaccharides
• CPC Class Codes: A61L 27/52 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 27/54 : Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61P 17/00 : Drugs for dermatological disorders
• CPC Class Codes: A61P 23/00 : Anaesthetics
• CPC Class Codes: A61P 23/02 : Local anaesthetics
• CPC Class Codes: A61P 29/00 : Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61Q 19/001 : Preparations for care of the lips
• CPC Class Codes: A61Q 19/08 : Anti-ageing preparations
• CPC Class Codes: C08L 5/08 : Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof

Abstract

Disclosed herein are cohesive soft tissue fillers, for example, dermal and subdermal fillers, based on hyaluronic acids and pharmaceutically acceptable salts thereof. In one aspect, hyaluronic acid-based compositions described herein include a therapeutically effective amount of at least one anesthetic agent, for example, lidocaine. The present hyaluronic acid-based compositions including lidocaine have an enhanced stability and cohesivity, relative to conventional compositions including lidocaine, for example when subjected to sterilization techniques or when stored for long periods of time. Methods and processes of preparing such hyaluronic acid-based compositions are also provided.

Claims

1. A dermal filler comprising:

hyaluronic acid (HA) crosslinked with 1,4 butanediol diglycidyl ether (BDDE), and

lidocaine;

wherein the lidocaine is freely released in vivo;

wherein the dermal filler is sterile; and

wherein the dermal filler is made by a process comprising;

crosslinking HA with BDDE to obtain a crosslinked HA composition;

adding lidocaine to the crosslinked HA composition; and

heat sterilizing the crosslinked HA composition with added lidocaine to obtain a sterile dermal filler.

2. The dermal filler of claim 1, wherein the process further comprises adjusting the pH of the crosslinked HA composition to obtain an alkaline crosslinked HA composition.

3. The dermal filler of claim 2, wherein the pH adjustment is performed before adding the lidocaine.

4. The dermal filler of claim 2, wherein the pH adjustment comprises adjusting the pH to about 7.5 to about 8.0.

5. The dermal filler of claim 2, wherein the pH adjustment comprises adjusting the pH to above about 7.5.

6. The dermal filler of claim 1, wherein the adding the lidocaine comprises adding a solution containing lidocaine HCl.

7. The dermal filler of claim 1, wherein the process further comprises passing the crosslinked HA composition through a sieve before adding the lidocaine.

8. The dermal filler of claim 7, wherein the process further comprises adding free HA gel to the crosslinked HA composition after the crosslinked HA composition has been passed through the sieve.

9. The dermal filler of claim 7, wherein the crosslinked HA composition, after being passed through the sieve, comprises particles of crosslinked HA having an average particle size of at least about 200 μ

m.

10. The dermal filler of claim 7, wherein the crosslinked HA composition, after being passed through the sieve, comprises particles of crosslinked HA having an average particle size of at least about 250 μ

m.

11. The dermal filler of claim 7, wherein the crosslinked HA composition, after being passed through the sieve, comprises particles of crosslinked HA having an average particle size of less than about 200 μ

m.

12. The dermal filler of claim 1, wherein the process further comprises homogenizing the crosslinked HA composition before adding the lidocaine.

13. The dermal filler of claim 1, wherein the dermal filler has a lidocaine concentration of between about 0.1% and about 5.0% w/w.

14. The dermal filler of claim 1, wherein the dermal filler has a HA concentration between about 20 mg/mL and about 30 mg/mL.

15. The dermal filler of claim 1, having a lidocaine concentration of 0.3% w/w and a HA concentration between about 20 mg/mL and about 30 mg/mL.

16. A dermal filler composition comprising:

a composition comprising hyaluronic acid (HA) crosslinked with 1,4 butanediol diglycidyl ether (BDDE), wherein the HA is not crosslinked to a non-HA biopolymer, and lidocaine;

wherein the dermal filler is made by a process comprising;

crosslinking HA with BDDE to obtain a crosslinked HA;

adding lidocaine to the crosslinked HA; and

heat sterilizing the crosslinked HA with added lidocaine to obtain a sterile dermal filler.

17. The dermal filler of claim 16, wherein the process further comprises adjusting the pH of the crosslinked HA to obtain an alkaline crosslinked HA.

18. The dermal filler of claim 17, wherein the adjusting the pH is performed before adding the lidocaine.

19. The dermal filler of claim 16, wherein adding the lidocaine comprises adding a solution containing lidocaine HCl.

20. The dermal filler of claim 16, wherein the crosslinked HA comprises particles of crosslinked HA having an average particle size of at least about 200 μ

m.

21. The dermal filler of claim 16, wherein the crosslinked HA comprises particles of crosslinked HA having an average particle size of less than about 200 μ

m.

22. The dermal filler of claim 16, wherein the dermal filler has a lidocaine concentration of between about 0.1% and about 5.0% w/w.

23. The dermal filler of claim 16, wherein the dermal filler has a HA concentration of between about 20 mg/mL and about 30 mg/mL.

24. A dermal filler composition comprising:

a hyaluronic acid (HA) crosslinked with 1,4 butanediol diglycidyl ether (BDDE), and about 0.3% lidocaine by weight, wherein the lidocaine is freely released in vivo and wherein the composition is sterile;

wherein the composition is made by a process comprising;

crosslinking HA with BDDE to obtain a crosslinked HA;

adding a free HA gel to the crosslinked HA;

adding a solution of lidocaine HCl to the crosslinked HA; and

autoclaving the crosslinked HA having free HA gel and lidocaine HCl added thereto, to obtain a sterile dermal filler composition.

25. A dermal filler product comprising:

a dermal filler composition comprising a hyaluronic acid (HA) crosslinked with 1,4 butanediol diglycidyl ether (BDDE), and between about 0.1% to about 5.0% lidocaine by weight, wherein the HA is not crosslinked to a non-HA biopolymer, and wherein the composition is sterile;

a syringe containing the sterile composition;

wherein the product is made by a process comprising;

crosslinking HA with BDDE to obtain a crosslinked HA;

adding lidocaine to the crosslinked HA to obtain a crosslinked HA containing lidocaine; and

packaging the crosslinked HA containing lidocaine in a syringe; and

autoclaving the syringe containing the crosslinked HA containing lidocaine to obtain a dermal filler product.

26. The dermal filler product of claim 25, wherein the sterile composition contained in the syringe has a volume between about 0.8 mL and about 2.5 mL.

27. The dermal filler product of claim 25, wherein the sterile composition has a HA concentration of about 20 mg/mL to about 30 mg/mL.

28. The dermal filler product of claim 25, wherein the sterile composition is stable at ambient temperature for at least about 6 months.

29. The dermal filler product of claim 25, wherein the sterile composition comprises particles of crosslinked HA having an average particle size of at least about 200 μ

m.

30. The dermal filler product of claim 25, wherein the sterile composition comprises particles of crosslinked HA having an average particle size of less than about 200 μ

m.