IP Library Granted Patent US 11,273,131
Granted Patent B2
US 11,273,131 · App. 15/724,234 · Granted Mar 15, 2022

Pharmaceutical compositions with enhanced permeation

Inventors: Alexander Mark Schobel (Whitehouse Station, NJ); Stephanie Marie Varjan (Oradell, NJ); Stephen Paul Wargacki (Annandale, NJ)
Assignee: AQUESTIVE THERAPEUTICS, INC.
A61K9/7007A61K9/006A61K31/05A61K31/085A61K31/137A61K31/335A61K31/36A61K31/5513A61K31/5517A61K36/61A61K47/10A61K47/12A61K47/14A61K47/26A61K47/38A61M37/0015A61M2037/0023
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Quick Facts
Patent No.
US 11,273,131
App. No.
15/724,234
Granted
Mar 15, 2022
Kind
B2
Abstract

Pharmaceutical compositions having enhanced active component permeation properties are described.

Claims (68)

1. A pharmaceutical composition, comprising:

a polymeric matrix comprising a polyethylene oxide, a cellulosic polymer, a hydroxypropyl methylcellulose, a polyvinylpyrrolidone, a polysaccharide, a polyethylene oxide and a polyvinylpyrrolidone, a polyethylene oxide and a polysaccharide, a polyethylene oxide, and hydroxypropyl methylcellulose and a polysaccharide, a polyethylene oxide and a hydroxypropyl methylcellulose and a polysaccharide and a polyvinylpyrrolidone, a cellulosic polymer and a polysaccharide, a cellulosic polymer and a polyvinylpyrrolidone, a hydroxypropyl methylcellulose and polyvinylpyrrolidone, a dendritic polymer, or a hyperbranched polymer;

a pharmaceutically active component including a benzodiazepine in the polymeric matrix; and

an adrenergic receptor interacter.

2. The pharmaceutical composition according to claim 1 , wherein the pharmaceutical composition further includes a permeation enhancer.

3. The pharmaceutical composition according to claim 1 , wherein the adrenergic receptor interacter includes a terpenoid, a terpene, or a sesquiterpene.

4. The pharmaceutical composition according to claim 2 , wherein the permeation enhancer includes farnesol or Labrasol.

5. The pharmaceutical composition according to claim 2 , wherein the permeation enhancer includes linoleic acid.

6. The pharmaceutical composition according to claim 1 , wherein the pharmaceutical composition is a film further comprising a polymeric matrix, the pharmaceutically active component being contained in the polymeric matrix.

7. The pharmaceutical composition according to claim 1 , wherein the adrenergic receptor interacter includes a phenylpropanoid.

8. The pharmaceutical composition according to claim 7 , wherein the phenylpropanoid is eugenol or eugenol acetate.

9. The pharmaceutical composition according to claim 7 , wherein the phenylpropanoid is a cinnamic acid, cinnamic acid ester, cinnamic aldehyde or hydrocinnamic acid.

10. The pharmaceutical composition according to claim 7 , wherein the phenylpropanoid is chavicol.

11. The pharmaceutical composition according to claim 7 , wherein the phenylpropanoid is safrole.

12. The pharmaceutical composition according to claim 1 , wherein the adrenergic receptor interacter is a phytoextract.

13. The pharmaceutical composition according to claim 12 , wherein the phytoextract further includes an essential oil extract of a clove plant.

14. The pharmaceutical composition according to claim 12 , wherein the phytoextract further includes an essential oil extract of a leaf of a clove plant.

15. The pharmaceutical composition according to claim 12 , wherein the phytoextract further includes an essential oil extract of a flower bud of a clove plant.

16. The pharmaceutical composition according to claim 12 , wherein the phytoextract further includes an essential oil extract of a stem of a clove plant.

17. The pharmaceutical composition according to claim 12 , wherein the phytoextract is synthetic or biosynthetic.

18. The pharmaceutical composition according to claim 12 , wherein the phytoextract further includes 40-95% eugenol.

19. The pharmaceutical composition according to claim 1 , wherein the polymer matrix includes a water soluble polymer.

20. The pharmaceutical composition according to claim 1 , wherein the polymer matrix includes a cellulosic polymer selected from the group of: hydroxyethyl cellulose, hydroxyethylmethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, and carboxymethyl cellulose.

21. The pharmaceutical composition according to claim 1 , wherein the pharmaceutical composition is a chewable or gelatin based dosage form, spray, gum, gel, cream, tablet, liquid or film.

22. The pharmaceutical composition according to claim 1 , wherein the polymeric matrix comprises a polyethylene oxide, cellulosic polymer, polyethylene oxide and polyvinyl pyrrolidone, polyethylene oxide and a polysaccharide, polyethylene oxide, hydroxypropyl methylcellulose and a polysaccharide, or polyethylene oxide, hydroxypropyl methylcellulose, polysaccharide and polyvinylpyrrolidone.

23. The pharmaceutical composition according to claim 1 , wherein the polymeric matrix further comprises at least one polymer selected from the group of: pullulan, polyvinyl pyrrolidone, polyvinyl alcohol, sodium alginate, polyethylene glycol, xanthan gum, tragancanth gum, guar gum, acacia gum, arabic gum, polyacrylic acid, methylmethacrylate copolymer, carboxyvinyl copolymers, starch, gelatin, ethylene oxide, propylene oxide co-polymers, collagen, albumin, poly-amino acids, polyphosphazenes, polysaccharides, chitin, and chitosan.

24. The pharmaceutical composition according to claim 1 , further comprising a stabilizer.

25. The pharmaceutical composition according to claim 1 , wherein the polymeric matrix comprises a dendritic polymer or a hyperbranched polymer.

26. A pharmaceutical composition, comprising:

a polymeric matrix comprising a cellulosic polymer, a hydroxypropyl methylcellulose, polyvinylpyrrolidone, a polysaccharide, a polyethylene oxide, polyethylene oxide and polyvinyl pyrrolidone, polyethylene oxide and a polysaccharide, polyethylene oxide and hydroxypropyl methylcellulose and a polysaccharide, polyethylene oxide and hydroxypropyl methylcellulose and a cellulosic polymer and a polysaccharide, a cellulosic polymer and a polyvinylpyrrolidone, a polysaccharide and a polyvinylpyrrolidone, a hydroxypropyl methylcellulose and a polyvinylpyrrolidone, a dendritic polymer or a hyperbranched polymer;

a stabilizer;

a pharmaceutically active component including a benzodiazepine in the polymeric matrix; and

an adrenergic receptor interacter.

27. The pharmaceutical composition according to claim 26 , wherein the adrenergic receptor interacter includes eugenol or eugenol acetate.

28. The pharmaceutical composition according to claim 26 , wherein the adrenergic receptor interacter includes a cinnamic acid, cinnamic acid ester, cinnamic aldehyde or hydrocinnamic acid.

29. The pharmaceutical composition according to claim 26 , wherein the adrenergic receptor interacter includes chavicol.

30. The pharmaceutical composition according to claim 26 , wherein the adrenergic receptor interacter includes safrole.

31. The pharmaceutical composition according to claim 26 , wherein the adrenergic receptor interacter includes an essential oil extract of a clove plant.

32. The pharmaceutical composition according to claim 26 , wherein the adrenergic receptor interacter includes an essential oil extract of a leaf of a clove plant.

33. The pharmaceutical composition according to claim 26 , wherein the adrenergic receptor interacter includes an essential oil extract of a flower bud of a clove plant.

34. The pharmaceutical composition according to claim 26 , wherein the adrenergic receptor interacter includes an essential oil extract of a stem of a clove plant.

35. The pharmaceutical composition according to claim 26 , wherein the phytoextract is synthetic or biosynthetic.

36. The pharmaceutical composition according to claim 26 , wherein the adrenergic receptor interacter includes 40-95% eugenol.

37. The pharmaceutical composition according to claim 26 , wherein the polymer matrix includes a cellulosic polymer selected from the group of: hydroxyethyl cellulose, hydroxyethylmethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, and carboxymethyl cellulose.

38. The pharmaceutical composition according to claim 26 , wherein the polymeric matrix comprises a polyethylene oxide, cellulosic polymer, polyethylene oxide and polyvinyl pyrrolidone, polyethylene oxide and a polysaccharide, polyethylene oxide and hydroxypropyl methylcellulose and a polysaccharide, or polyethylene oxide and hydroxypropyl methylcellulose, and polysaccharide and polyvinylpyrrolidone.

39. The pharmaceutical composition according to claim 26 , wherein the polymeric matrix comprises a dendritic polymer, or a hyperbranched polymer.

40. The pharmaceutical composition according to claim 1 , wherein the polymeric matrix comprises a polyethylene oxide.

41. The pharmaceutical composition according to claim 26 , wherein the polymeric matrix comprises a polyethylene oxide.

42. The pharmaceutical composition according to claim 1 , wherein the polymeric matrix comprises a polyvinylpyrrolidone.

43. The pharmaceutical composition according to claim 26 , wherein the polymeric matrix comprises a polyvinylpyrrolidone.

44. The pharmaceutical composition according to claim 1 , wherein the polymeric matrix comprises a polysaccharide.

45. The pharmaceutical composition according to claim 26 , wherein the polymeric matrix comprises a polysaccharide.

46. The pharmaceutical composition according to claim 1 , wherein the polymeric matrix comprises a cellulosic polymer and a polysaccharide.

47. The pharmaceutical composition according to claim 26 , wherein the polymeric matrix comprises a cellulosic polymer and a polysaccharide.

48. The pharmaceutical composition according to claim 1 , wherein the polymeric matrix comprises a cellulosic polymer and polyvinylpyrrolidone.

49. The pharmaceutical composition according to claim 26 , wherein the polymeric matrix comprises a cellulosic polymer and polyvinylpyrrolidone.

50. The pharmaceutical composition according to claim 1 , wherein the polymeric matrix comprises a hydroxypropyl methylcellulose and a polyvinylpyrrolidone.

51. The pharmaceutical composition according to claim 26 , wherein the polymeric matrix comprises a hydroxypropyl methylcellulose and a polyvinylpyrrolidone.

52. The pharmaceutical composition according to claim 1 , further comprising benzyl alcohol.

53. The pharmaceutical composition according to claim 26 , further comprising benzyl alcohol.

54. The pharmaceutical composition according to claim 1 , wherein the benzodiazepine is diazepam.

55. The pharmaceutical composition according to claim 26 , wherein the benzodiazepine is diazepam.

56. A pharmaceutical composition, comprising:

a polymeric matrix comprising a cellulosic polymer, a polyvinylpyrrolidone, or a cellulosic polymer and a polyvinylpyrrolidone;

a pharmaceutically active component including diazepam in the polymeric matrix; and

an adrenergic receptor interacter.

57. The pharmaceutical composition according to claim 56 , wherein the adrenergic receptor interacter includes eugenol, eugenol acetate, clove oil, a cinnamic acid, cinnamic acid ester, cinnamic aldehyde, or hydrocinnamic acid.

58. The pharmaceutical composition according to claim 56 , further comprising benzyl alcohol.

Assignments (9)
RELEASE OF SECURITY INTEREST Recorded May 13, 2026
From: U.S. BANK TRUST COMPANY, NATIONAL ASSOCIATION
To: AQUESTIVE THERAPEUTICS, INC.
Reel/Frame 075646/0258 →
SECURITY INTEREST Recorded May 12, 2026
From: AQUESTIVE THERAPEUTICS, INC.
To: OAKTREE FUND ADMINISTRATION, LLC, AS ADMINISTRATIVE AGENT
Reel/Frame 075561/0782 →
SECURITY INTEREST Recorded Nov 2, 2023
From: AQUESTIVE THERAPEUTICS, INC.
To: U.S. BANK TRUST COMPANY, NATIONAL ASSOCIATION
Reel/Frame 065446/0494 →
RELEASE OF SECURITY INTEREST Recorded Nov 1, 2023
From: U.S. BANK TRUST COMPANY NATIONAL ASSOCIATION (AS SUCCESSOR IN INTEREST TO U.S BANK NATIONAL ASSOCIATION)
To: AQUESTIVE THERAPEUTICS, INC.
Reel/Frame 065426/0642 →
RELEASE OF SECURITY INTEREST Recorded Jul 15, 2019
From: PERCEPTIVE CREDIT HOLDINGS, LP
To: AQUESTIVE THERAPEUTICS, INC.; MONOSOL RX, INC.; MSRX US, LLC
Reel/Frame 049757/0733 →
SECURITY INTEREST Recorded Jul 15, 2019
From: AQUESTIVE THERAPEUTICS, INC.
To: U.S. BANK NATIONAL ASSOCIATION
Reel/Frame 049758/0082 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 2, 2018
From: SCHOBEL, ALEXANDER MARK; VARJAN, STEPHANIE MARIE; WARGACKI, STEPHEN PAUL
To: AQUESTIVE THERAPEUTICS, INC.
Reel/Frame 045419/0851 →
AMENDMENT TO PATENT SECURITY AGREEMENT RECORDED AT REEL/FRAME 039707/0194 Recorded Jan 30, 2018
From: AQUESTIVE THERAPEUTICS, INC.
To: PERCEPTIVE CREDIT HOLDINGS, LP
Reel/Frame 045279/0802 →
CHANGE OF NAME Recorded Jan 29, 2018
From: MONOSOL RX, LLC
To: AQUESTIVE THERAPEUTICS, INC.
Reel/Frame 045196/0389 →
Continuity (4)
Continuation In Part 15717856 · Sep 27, 2017
Continuation In Part 15587376 · May 4, 2017
Provisional Application 62331993 · May 5, 2016
Related Publication 20180200198A1 · Jul 19, 2018
Cited By (1)
US 12,465,564