IP Library › Granted Patent US 9,867,810

Granted Patent B1

US 9,867,810 · App. 15/680,967 · Granted Jan 16, 2018

Ophthalmic pharmaceutical compositions and uses relating thereto

Inventors: Claes Feinbaum (Herzliya, IL); Franc Salamun (Nova Gorica, SI); Sudhir Patel (Stirling, GB)

Assignee: Orasis Pharmaceuticals Ltd.

A61K31/4178 A61K31/365 A61K47/36

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Quick Facts

Patent No.: US 9,867,810
App. No.: 15/680,967
Granted: Jan 16, 2018
Kind: B1

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Abstract

The disclosure relates to ophthalmic pharmaceutical compositions comprising pilocarpine or a pharmaceutically acceptable salt. Aspects of the disclosure further relate to uses and preparations of ophthalmic pharmaceutical compositions comprising pilocarpine or a pharmaceutically acceptable salt, for correcting presbyopia and other ocular conditions in a subject.

Claims (190)

1. An ophthalmic pharmaceutical composition comprising pilocarpine or a pharmaceutically acceptable salt thereof at a concentration of 0.01% (w/w or w/v) to 0.4% (w/w or w/v), hydroxypropyl methylcellulose at a concentration of 0.1% (w/w or w/v) to 2.0% (w/w or w/v), sodium hyaluronate at a concentration of 0.01% (w/w or w/v) to 0.9% (w/w or w/v), and a pharmaceutically acceptable carrier.

2. The ophthalmic pharmaceutical composition of claim 1 , wherein the pilocarpine salt is pilocarpine hydrochloride or pilocarpine nitrate.

3. The ophthalmic pharmaceutical composition of claim 1 , further comprising diclofenac or a pharmaceutically acceptable salt thereof at a concentration of 0.001% (w/w or w/v) to 0.090% (w/w or w/v), or ketorolac or a pharmaceutically acceptable salt thereof at a concentration of 0.01% (w/w or w/v) to 0.60% (w/w or w/v).

4. The ophthalmic pharmaceutical composition of claim 3 , wherein the diclofenac salt is diclofenac sodium, or wherein the ketorolac salt is ketorolac tromethamine.

5. The ophthalmic pharmaceutical composition of claim 4 , wherein the ophthalmic pharmaceutical composition comprises:

(1) pilocarpine hydrochloride or pilocarpine nitrate at a concentration of 0.1% (w/w or w/v) to 0.4% (w/w or w/v), hydroxypropyl methylcellulose at a concentration of 0.1% (w/w or w/v) to 1.2% (w/w or w/v), sodium hyaluronate at a concentration of 0.01% (w/w or w/v) to 0.2% (w/w or w/v), and diclofenac sodium at a concentration of 0.001% (w/w or w/v) to 0.012% (w/w or w/v); or

(2) pilocarpine hydrochloride or pilocarpine nitrate at a concentration of 0.1% (w/w or w/v) to 0.4% (w/w or w/v), hydroxypropyl methylcellulose at a concentration of 0.1% (w/w or w/v) to 1.2% (w/w or w/v), sodium hyaluronate at a concentration of 0.01% (w/w or w/v) to 0.2% (w/w or w/v), and ketorolac tromethamine at a concentration of 0.01% (w/w or w/v) to 0.50% (w/w or w/v).

6. The ophthalmic pharmaceutical composition of claim 5 , wherein the ophthalmic pharmaceutical composition comprises:

(1) pilocarpine hydrochloride or pilocarpine nitrate at a concentration of 0.2% (w/w or w/v), hydroxypropyl methylcellulose at a concentration of 0.8% (w/w or w/v), sodium hyaluronate at a concentration of 0.1% (w/w or w/v), and diclofenac sodium at a concentration of 0.006% (w/w or w/v); or

(2) pilocarpine hydrochloride or pilocarpine nitrate at a concentration of 0.2% (w/w or w/v), hydroxypropyl methylcellulose at a concentration of 0.8% (w/w or w/v), sodium hyaluronate at a concentration of 0.1% (w/w or w/v), and ketorolac tromethamine at a concentration of 0.50% (w/w or w/v).

7. The ophthalmic pharmaceutical composition of claim 2 , wherein the ophthalmic pharmaceutical composition comprises:

(1) pilocarpine hydrochloride or pilocarpine nitrate at a concentration of 0.1% (w/w or w/v) to 0.4% (w/w or w/v), hydroxypropyl methylcellulose at a concentration of 0.1% (w/w or w/v) to 1.2% (w/w or w/v), and further comprising sodium hyaluronate at a concentration of 0.01% (w/w or w/v) to 0.2% (w/w or w/v), or diclofenac sodium at a concentration of 0.001% (w/w or w/v) to 0.012% (w/w or w/v), or mixtures thereof; or

(2) pilocarpine hydrochloride or pilocarpine nitrate at a concentration of 0.1% (w/w or w/v) to 0.4% (w/w or w/v), hydroxypropyl methylcellulose at a concentration of 0.1% (w/w or w/v) to 1.2% (w/w or w/v), and further comprising sodium hyaluronate at a concentration of 0.01% (w/w or w/v) to 0.2% (w/w or w/v), or ketorolac tromethamine at a concentration of 0.01% (w/w or w/v) to 0.50% (w/w or w/v), or mixtures thereof.

8. The ophthalmic pharmaceutical composition of claim 7 , wherein the ophthalmic pharmaceutical composition comprises:

(1) pilocarpine hydrochloride or pilocarpine nitrate at a concentration of 0.2% (w/w or w/v), hydroxypropyl methylcellulose at a concentration of 0.8% (w/w or w/v), and further comprising sodium hyaluronate at a concentration of 0.1% (w/w or w/v), or diclofenac sodium at a concentration of 0.006% (w/w or w/v), or mixtures thereof; or

(2) pilocarpine hydrochloride or pilocarpine nitrate at a concentration of 0.2% (w/w or w/v), hydroxypropyl methylcellulose at a concentration of 0.8% (w/w or w/v), and further comprising sodium hyaluronate at a concentration of 0.1% (w/w or w/v), or ketorolac tromethamine at a concentration of 0.50% (w/w or w/v), or mixtures thereof.

9. The ophthalmic pharmaceutical composition of claim 1 , wherein the ophthalmic pharmaceutical composition comprises a pharmaceutically acceptable diluent, preservative, and/or solvent.

10. The ophthalmic pharmaceutical composition of claim 1 , further comprising an isotonic agent, a wetting agent, a buffer, a stabilizer, a pH agent, a solubilizer, a thickening agent, and/or a dispersing agent.

11. The ophthalmic pharmaceutical composition of claim 1 , wherein the ophthalmic pharmaceutical composition is effective for correction of presbyopia for up to 24 hours.

12. A method of correcting presbyopia in a subject comprising administering to the subject a therapeutically effective amount of an ophthalmic pharmaceutical composition comprising pilocarpine or a pharmaceutically acceptable salt thereof at a concentration of 0.01% (w/w or w/v) to 0.4% (w/w or w/v), hydroxypropyl methylcellulose at a concentration of 0.1% (w/w or w/v) to 2.0% (w/w or w/v), sodium hyaluronate at a concentration of 0.01% (w/w or w/v) to 0.9% (w/w or w/v), and a pharmaceutically acceptable carrier.

13. The method of claim 12 , wherein the pilocarpine salt is pilocarpine hydrochloride or pilocarpine nitrate.

14. The method of claim 12 , wherein the ophthalmic pharmaceutical composition further comprises diclofenac or a pharmaceutically acceptable salt thereof at a concentration of 0.001% (w/w or w/v) to 0.090% (w/w or w/v), or ketorolac or a pharmaceutically acceptable salt thereof at a concentration of 0.01% (w/w or w/v) to 0.60% (w/w or w/v).

15. The method of claim 14 , wherein the diclofenac salt is diclofenac sodium, or wherein the ketorolac salt is ketorolac tromethamine.

16. The method of claim 15 , wherein the ophthalmic pharmaceutical composition comprises:

17. The method of claim 16 , wherein the ophthalmic pharmaceutical composition comprises:

18. The method of claim 13 , wherein the ophthalmic pharmaceutical composition comprises:

(1) pilocarpine hydrochloride or pilocarpine nitrate at a concentration of 0.1 (w/w or w/v) to 0.4% (w/w or w/v), hydroxypropyl methylcellulose at a concentration of 0.1% (w/w or w/v) to 1.2% (w/w or w/v), and further comprising sodium hyaluronate at a concentration of 0.01% (w/w or w/v) to 0.2% (w/w or w/v), or diclofenac sodium at a concentration of 0.001% (w/w or w/v) to 0.012% (w/w or w/v), or mixtures thereof; or

(2) pilocarpine hydrochloride or pilocarpine nitrate at a concentration of 0.1% (w/w or w/v) to 0.4% (w/w or w/v), hydroxypropyl methylcellulose at a concentration of 0.1% (w/w or w/v) to 1.2% (w/w or w/v), and further comprising sodium hyaluronate at a concentration of 0.01% (w/w or w/v) to 0.2% (w/w or w/v), or ketorolac tromethamine at a concentration of 0.01% (w/w or w/v) to 0.50% (w/w or w/v), or mixtures thereof.

19. The method of claim 18 , wherein the ophthalmic pharmaceutical composition comprises:

20. The method of claim 13 , wherein the ophthalmic pharmaceutical composition comprises a pharmaceutically acceptable diluent, preservative, and/or solvent.

21. The method of claim 13 , wherein the ophthalmic pharmaceutical composition further comprises an isotonic agent, a wetting agent, a buffer, a stabilizer, a pH agent, a solubilizer, a thickening agent, and/or a dispersing agent.

22. The method of claim 13 , wherein the ophthalmic pharmaceutical composition is effective for correction of presbyopia for up to 24 hours.

23. The method of claim 13 , wherein the administration is topical or by surgical intervention.

24. The method of claim 13 , wherein the subject:

a) is a spectacle wearer who cannot or will not use progressive or bifocal lenses;

b) underwent cataract surgery;

c) developed presbyopia after a corneal procedure;

d) has mono-focal or multifocal intraocular lenses;

e) uses contact lenses and does not tolerate mono-vision contact lenses;

f) uses contact lenses and does not tolerate multifocal contact lenses;

g) suffers from a higher order aberration after corneal surgery;

h) suffers from hyperopia or tropias;

i) does not tolerate a change in spectacle prescription;

j) experiences a rapid change in spectacle prescription;

k) is at risk of falls when using progressive or bifocal lenses; and/or

l) suffers from a higher order aberration at night or under dull light conditions.

25. A method of increasing the depth of field in a subject's eye comprising administering to the subject a therapeutically effective amount of an ophthalmic pharmaceutical composition comprising pilocarpine or a pharmaceutically acceptable salt thereof at a concentration of 0.01% (w/w or w/v) to 0.4% (w/w or w/v), hydroxypropyl methylcellulose at a concentration of 0.1% (w/w or w/v) to 2.0% (w/w or w/v), and a pharmaceutically acceptable carrier.

26. The method of claim 25 , wherein the pilocarpine salt is pilocarpine hydrochloride or pilocarpine nitrate.

27. The method of claim 26 , wherein the ophthalmic pharmaceutical composition further comprises sodium hyaluronate at a concentration of 0.01% (w/w or w/v) to 0.9% (w/w or w/v).

28. The method of claim 27 , wherein the ophthalmic pharmaceutical composition further comprises diclofenac or a pharmaceutically acceptable salt thereof at a concentration of 0.001% (w/w or w/v) to 0.090% (w/w or w/v), or ketorolac or a pharmaceutically acceptable salt thereof at a concentration of 0.01% (w/w or w/v) to 0.60% (w/w or w/v).

29. The method of claim 28 , wherein the diclofenac salt is diclofenac sodium, or wherein the ketorolac salt is ketorolac tromethamine.

30. The method of claim 29 , wherein the ophthalmic pharmaceutical composition comprises:

31. The method of claim 30 , wherein the ophthalmic pharmaceutical composition comprises:

32. The method of claim 26 , wherein the ophthalmic pharmaceutical composition further comprises:

(1) sodium hyaluronate at a concentration of 0.01% (w/w or w/v) to 0.9% (w/w or w/v), or diclofenac sodium at a concentration of 0.001% (w/w or w/v) to 0.090% (w/w or w/v), or mixtures thereof; or

(2) sodium hyaluronate at a concentration of 0.01% (w/w or w/v) to 0.9% (w/w or w/v), or ketorolac tromethamine at a concentration of 0.01% (w/w or w/v) to 0.60% (w/w or w/v), or mixtures thereof.

33. The method of claim 26 , wherein the ophthalmic pharmaceutical composition comprises:

(1) pilocarpine hydrochloride or pilocarpine nitrate at a concentration of 0.1% (w/w or w/v) to 0.4% (w/w or w/v), hydroxypropyl methylcellulose at a concentration of 0.1% (w/w or w/v) to 1.2% (w/w or w/v), and further comprising sodium hyaluronate at a concentration of 0.01% (w/w or w/v) to 0.2% (w/w or w/v), or diclofenac sodium at a concentration of 0.001% (w/w or w/v) to 0.012% (w/w or w/v), or mixtures thereof; or

(2) pilocarpine hydrochloride or pilocarpine nitrate at a concentration of 0.1% (w/w or w/v) to 0.4% (w/w or w/v), hydroxypropyl methylcellulose at a concentration of 0.1% (w/w or w/v) to 1.2% (w/w or w/v), and further comprising sodium hyaluronate at a concentration of 0.01% (w/w or w/v) to 0.2% (w/w or w/v), or ketorolac tromethamine at a concentration of 0.01% (w/w or w/v) to 0.50% (w/w or w/v), or mixtures thereof.

34. The method of claim 33 , wherein the ophthalmic pharmaceutical composition comprises:

35. The method of claim 25 , wherein the ophthalmic pharmaceutical composition comprises a pharmaceutically acceptable diluent, preservative, and/or solvent.

36. The method of claim 25 , wherein the ophthalmic pharmaceutical composition further comprises an isotonic agent, a wetting agent, a buffer, a stabilizer, a pH agent, a solubilizer, a thickening agent, and/or a dispersing agent.

37. A method of reducing the size of a pupil in a subject comprising administering to the subject a therapeutically effective amount of an ophthalmic pharmaceutical composition comprising pilocarpine or a pharmaceutically acceptable salt thereof at a concentration of 0.01% (w/w or w/v) to 0.4% (w/w or w/v), hydroxypropyl methylcellulose at a concentration of 0.1% (w/w or w/v) to 2.0% (w/w or w/v), sodium hyaluronate at a concentration of 0.01% (w/w or w/v) to 0.9% (w/w or w/v), and a pharmaceutically acceptable carrier.

38. The method of claim 37 , wherein the pilocarpine salt is pilocarpine hydrochloride or pilocarpine nitrate.

39. The method of claim 37 , wherein the ophthalmic pharmaceutical composition further comprises diclofenac or a pharmaceutically acceptable salt thereof at a concentration of 0.001% (w/w or w/v) to 0.090% (w/w or w/v), or ketorolac or a pharmaceutically acceptable salt thereof at a concentration of 0.01% (w/w or w/v) to 0.60% (w/w or w/v).

40. The method of claim 39 , wherein the diclofenac salt is diclofenac sodium, or wherein the ketorolac salt is ketorolac tromethamine.

41. The method of claim 40 , wherein the ophthalmic pharmaceutical composition comprises:

42. The method of claim 41 , wherein the ophthalmic pharmaceutical composition comprises:

43. The method of claim 38 , wherein the ophthalmic pharmaceutical composition comprises:

(1) pilocarpine hydrochloride or pilocarpine nitrate at a concentration of 0.1% (w/w or w/v) to 0.4% (w/w or w/v), hydroxypropyl methylcellulose at a concentration of 0.1% (w/w or w/v) to 1.2% (w/w or w/v), and further comprising sodium hyaluronate at a concentration of 0.01% (w/w or w/v) to 0.2% (w/w or w/v), or diclofenac sodium at a concentration of 0.001% (w/w or w/v) to 0.012% (w/w or w/v), or mixtures thereof; or

(2) pilocarpine hydrochloride or pilocarpine nitrate at a concentration of 0.1% (w/w or w/v) to 0.4% (w/w or w/v), hydroxypropyl methylcellulose at a concentration of 0.1% (w/w or w/v) to 1.2% (w/w or w/v), and further comprising sodium hyaluronate at a concentration of 0.01% (w/w or w/v) to 0.2% (w/w or w/v), or ketorolac tromethamine at a concentration of 0.01% (w/w or w/v) to 0.50% (w/w or w/v), or mixtures thereof.

44. The method of claim 43 , wherein the ophthalmic pharmaceutical composition comprises:

(1) pilocarpine hydrochloride or pilocarpine nitrate at a concentration of 0.2% (w/w or w/v), hydroxypropyl methylcellulose at a concentration of 0.8% (w/w or w/v), and further comprising sodium hyaluronate at a concentration of 0.1% (w/w or w/v), diclofenac sodium at a concentration of 0.006% (w/w or w/v), or mixtures thereof; or

45. The method of claim 38 , wherein the ophthalmic pharmaceutical composition comprises a pharmaceutically acceptable diluent, preservative, and/or solvent.

46. The method of claim 38 , wherein the ophthalmic pharmaceutical composition further comprises an isotonic agent, a wetting agent, a buffer, a stabilizer, a pH agent, a solubilizer, a thickening agent, and/or a dispersing agent.

47. The method of claim 38 , wherein the administration is topical or by surgical intervention.

48. The method of claim 38 , wherein the subject:

a) is a spectacle wearer who cannot or will not use progressive or bifocal lenses;

b) underwent cataract surgery;

c) developed presbyopia after a corneal procedure;

d) has mono-focal or multifocal intraocular lenses;

e) uses contact lenses and does not tolerate mono-vision contact lenses;

f) uses contact lenses and does not tolerate multifocal contact lenses;

g) suffers from a higher order aberration after corneal surgery;

h) suffers from hyperopia or tropias;

i) does not tolerate a change in spectacle prescription;

j) experiences a rapid change in spectacle prescription;

k) is at risk of falls when using progressive or bifocal lenses; and/or

l) suffers from a higher order aberration at night or under dull light conditions.

49. An ophthalmic pharmaceutical composition comprising pilocarpine or a pharmaceutically acceptable salt thereof at a concentration of 0.01% (w/w or w/v) to 0.4% (w/w or w/v), hydroxypropyl methylcellulose at a concentration of 0.1% (w/w or w/v) to 2.0% (w/w or w/v), diclofenac or a pharmaceutically acceptable salt thereof at a concentration of 0.001% (w/w or w/v) to 0.090% (w/w or w/v) or ketorolac or a pharmaceutically acceptable salt thereof at a concentration of 0.01% (w/w or w/v) to 0.60% (w/w or w/v), and a pharmaceutically acceptable carrier.

50. The ophthalmic pharmaceutical composition of claim 49 , wherein the pilocarpine salt is pilocarpine hydrochloride or pilocarpine nitrate.

51. The ophthalmic pharmaceutical composition of claim 50 , further comprising sodium hyaluronate at a concentration of 0.01% (w/w or w/v) to 0.9% (w/w or w/v).

52. The ophthalmic pharmaceutical composition of claim 50 , wherein the diclofenac salt is diclofenac sodium, or wherein the ketorolac salt is ketorolac tromethamine.

53. The ophthalmic pharmaceutical composition of claim 52 , wherein the ophthalmic pharmaceutical composition comprises:

54. The ophthalmic pharmaceutical composition of claim 53 , wherein the ophthalmic pharmaceutical composition comprises:

55. The ophthalmic pharmaceutical composition of claim 50 , wherein the ophthalmic pharmaceutical composition comprises:

(1) pilocarpine hydrochloride or pilocarpine nitrate at a concentration of 0.1% (w/w or w/v) to 0.4% (w/w or w/v), hydroxypropyl methylcellulose at a concentration of 0.1% (w/w or w/v) to 1.2% (w/w or w/v), and further comprising sodium hyaluronate at a concentration of 0.01% (w/w or w/v) to 0.2% (w/w or w/v), or diclofenac sodium at a concentration of 0.001% (w/w or w/v) to 0.012% (w/w or w/v), or mixtures thereof; or

(2) pilocarpine hydrochloride or pilocarpine nitrate at a concentration of 0.1% (w/w or w/v) to 0.4% (w/w or w/v), hydroxypropyl methylcellulose at a concentration of 0.1% (w/w or w/v) to 1.2% (w/w or w/v), and further comprising sodium hyaluronate at a concentration of 0.01% (w/w or w/v) to 0.2% (w/w or w/v), or ketorolac tromethamine at a concentration of 0.01% (w/w or w/v) to 0.50% (w/w or w/v), or mixtures thereof.

56. The ophthalmic pharmaceutical composition of claim 55 , wherein the ophthalmic pharmaceutical composition comprises:

57. The ophthalmic pharmaceutical composition of claim 49 , wherein the ophthalmic pharmaceutical composition comprises a pharmaceutically acceptable diluent, preservative, and/or solvent.

58. The ophthalmic pharmaceutical composition of claim 49 , further comprising an isotonic agent, a wetting agent, a buffer, a stabilizer, a pH agent, a solubilizer, a thickening agent, and/or a dispersing agent.

59. The ophthalmic pharmaceutical composition of claim 49 , wherein the ophthalmic pharmaceutical composition is effective for correction of presbyopia for up to 24 hours.

60. A method of correcting presbyopia in a subject comprising administering to the subject a therapeutically effective amount of an ophthalmic pharmaceutical composition comprising pilocarpine or a pharmaceutically acceptable salt thereof at a concentration of 0.01% (w/w or w/v) to 0.4% (w/w or w/v), hydroxypropyl methylcellulose at a concentration of 0.1% (w/w or w/v) to 2.0% (w/w or w/v), diclofenac or a pharmaceutically acceptable salt thereof at a concentration of 0.001% (w/w or w/v) to 0.090% (w/w or w/v) or ketorolac or a pharmaceutically acceptable salt thereof at a concentration of 0.01% (w/w or w/v) to 0.60% (w/w or w/v), and a pharmaceutically acceptable carrier.

61. The method of claim 60 , wherein the pilocarpine salt is pilocarpine hydrochloride or pilocarpine nitrate.

62. The method of claim 61 , wherein the ophthalmic pharmaceutical composition further comprises sodium hyaluronate at a concentration of 0.01% (w/w or w/v) to 0.9% (w/w or w/v).

63. The method of claim 61 , wherein the diclofenac salt is diclofenac sodium, or wherein the ketorolac salt is ketorolac tromethamine.

64. The method of claim 63 , wherein the ophthalmic pharmaceutical composition comprises:

65. The method of claim 64 , wherein the ophthalmic pharmaceutical composition comprises:

66. The method of claim 61 , wherein the ophthalmic pharmaceutical composition comprises:

(2) pilocarpine hydrochloride or pilocarpine nitrate at a concentration of 0.1% (w/w or w/v) to 0.4% (w/w or w/v), hydroxypropyl methylcellulose at a concentration of 0.1% (w/w or w/v) to 1.2% (w/w or w/v), and further comprising sodium hyaluronate at a concentration of 0.01% (w/w or w/v) to 0.2% (w/w or w/v), or ketorolac tromethamine at a concentration of 0.01% (w/w or w/v) to 0.50% (w/w or w/v), or mixtures thereof.

67. The method of claim 66 , wherein the ophthalmic pharmaceutical composition comprises:

68. The method of claim 61 , wherein the ophthalmic pharmaceutical composition comprises a pharmaceutically acceptable diluent, preservative, and/or solvent.

69. The method of claim 61 , wherein the ophthalmic pharmaceutical composition further comprises an isotonic agent, a wetting agent, a buffer, a stabilizer, a pH agent, a solubilizer, a thickening agent, and/or a dispersing agent.

70. The method of claim 61 , wherein the ophthalmic pharmaceutical composition is effective for correction of presbyopia for up to 24 hours.

71. The method of claim 61 , wherein the administration is topical or by surgical intervention.

72. The method of claim 61 , wherein the subject:

a) is a spectacle wearer who cannot or will not use progressive or bifocal lenses;

b) underwent cataract surgery;

c) developed presbyopia after a corneal procedure;

d) has mono-focal or multifocal intraocular lenses;

e) uses contact lenses and does not tolerate mono-vision contact lenses;

f) uses contact lenses and does not tolerate multifocal contact lenses;

g) suffers from a higher order aberration after corneal surgery;

h) suffers from hyperopia or tropias;

i) does not tolerate a change in spectacle prescription;

j) experiences a rapid change in spectacle prescription;

k) is at risk of falls when using progressive or bifocal lenses; and/or

l) suffers from a higher order aberration at night or under dull light conditions.

73. A method of reducing the size of a pupil in a subject comprising administering to the subject a therapeutically effective amount of an ophthalmic pharmaceutical composition comprising pilocarpine or a pharmaceutically acceptable salt thereof at a concentration of 0.01% (w/w or w/v) to 0.4% (w/w or w/v), hydroxypropyl methylcellulose at a concentration of 0.1% (w/w or w/v) to 2.0% (w/w or w/v), diclofenac or a pharmaceutically acceptable salt thereof at a concentration of 0.001% (w/w or w/v) to 0.090% (w/w or w/v) or ketorolac or a pharmaceutically acceptable salt thereof at a concentration of 0.01% (w/w or w/v) to 0.60% (w/w or w/v), and a pharmaceutically acceptable carrier.

74. The method of claim 73 , wherein the pilocarpine salt is pilocarpine hydrochloride or pilocarpine nitrate.

75. The method of claim 74 , wherein the ophthalmic pharmaceutical composition further comprises sodium hyaluronate at a concentration of 0.01% (w/w or w/v) to 0.9% (w/w or w/v).

76. The method of claim 74 , wherein the diclofenac salt is diclofenac sodium, or wherein the ketorolac salt is ketorolac tromethamine.

77. The method of claim 76 , wherein the ophthalmic pharmaceutical composition comprises:

78. The method of claim 77 , wherein the ophthalmic pharmaceutical composition comprises:

79. The method of claim 74 , wherein the ophthalmic pharmaceutical composition comprises:

(1) pilocarpine hydrochloride or pilocarpine nitrate at a concentration of 0.1% (w/w or w/v) to 0.4% (w/w or w/v), hydroxypropyl methylcellulose at a concentration of 0.1% (w/w or w/v) to 1.2% (w/w or w/v), and further comprising sodium hyaluronate at a concentration of 0.01% (w/w or w/v) to 0.2% (w/w or w/v), or diclofenac sodium at a concentration of 0.001% (w/w or w/v) to 0.012% (w/w or w/v), or mixtures thereof; or

(2) pilocarpine hydrochloride or pilocarpine nitrate at a concentration of 0.1% (w/w or w/v) to 0.4% (w/w or w/v), hydroxypropyl methylcellulose at a concentration of 0.1% (w/w or w/v) to 1.2% (w/w or w/v), and further comprising sodium hyaluronate at a concentration of 0.01% (w/w or w/v) to 0.2% (w/w or w/v), or ketorolac tromethamine at a concentration of 0.01% (w/w or w/v) to 0.50% (w/w or w/v), or mixtures thereof.

80. The method of claim 79 , wherein the ophthalmic pharmaceutical composition comprises:

(1) pilocarpine hydrochloride or pilocarpine nitrate at a concentration of 0.2% (w/w or w/v), hydroxypropyl methylcellulose at a concentration of 0.8% (w/w or w/v), and further comprising sodium hyaluronate at a concentration of 0.1% (w/w or w/v), diclofenac sodium at a concentration of 0.006% (w/w or w/v), or mixtures thereof; or

81. The method of claim 74 , wherein the ophthalmic pharmaceutical composition comprises a pharmaceutically acceptable diluent, preservative, and/or solvent.

82. The method of claim 74 , further comprising an isotonic agent, a wetting agent, a buffer, a stabilizer, a pH agent, a solubilizer, a thickening agent, and/or a dispersing agent.

83. The method of claim 74 , wherein the administration is topical or by surgical intervention.

84. The method of claim 74 , wherein the subject:

a) is a spectacle wearer who cannot or will not use progressive or bifocal lenses;

b) underwent cataract surgery;

c) developed presbyopia after a corneal procedure;

d) has mono-focal or multifocal intraocular lenses;

e) uses contact lenses and does not tolerate mono-vision contact lenses;

f) uses contact lenses and does not tolerate multifocal contact lenses;

g) suffers from a higher order aberration after corneal surgery;

h) suffers from hyperopia or tropias;

i) does not tolerate a change in spectacle prescription;

j) experiences a rapid change in spectacle prescription;

k) is at risk of falls when using progressive or bifocal lenses; and/or

l) suffers from a higher order aberration at night or under dull light conditions.

Assignments (2)

SECURITY INTEREST Recorded Sep 19, 2024

From: ORASIS PHARMACEUTICALS LTD.

To: ANKURA TRUST COMPANY, LLC

Reel/Frame 068636/0531 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 1, 2017

From: FEINBAUM, CLAES; SALAMUN, FRANC; PATEL, SUDHIR

To: ORASIS PHARMACEUTICALS LTD.

Reel/Frame 044007/0612 →

Continuity (1)

Provisional Application 62377154 · Aug 19, 2016