Ocular iontophoresis device

• US 20070123814A1
• Filed: 12/09/2005
• Published: 05/31/2007
• Est. Priority Date: 11/29/2005
• Status: Active Grant

• Current Assignee: EyeGate Pharma S.A.S. (Kiora Pharmaceuticals Incorporated)
• Original Assignee: Eyegate Pharmasa
• Inventors: Roy, Pierre
• Granted Patent: US 8,099,162 B2
• Time in Patent Office: Days
• US Class Current: 604/20
• CPC Class Codes: A61F 9/0017 implantable in, or in contact with, the eye, e.g. ocular inserts
• CPC Class Codes: A61N 1/0424 Shape of the electrode
• CPC Class Codes: A61N 1/044 Shape of the electrode
• CPC Class Codes: A61N 1/0448 Drug reservoir

Abstract

The invention relates to a device of ocular iontophoresis for delivering active substances, comprising a reservoir having an outer wall and a hollow body at least partly delimited by the outer wall, wherein the hollow body is capable of receiving an electrical conductive medium and active substances contained in the medium and has an outlet defining a surface, so-called “application surface”, intended to receive a determine part of an eyeball surface, the application surface being at least partly limited by an outer line concave towards the optical axis of the eyeball, wherein the outer wall extends from the outer line with a global outwardly with respect to the said optical axis.

Claims

1. An ocular iontophoresis device for delivering active substances to an eyeball, the ocular iontophoresis device comprising:

a reservoir having an outer wall and a hollow body at least partly delimited by the outer wall,

wherein the hollow body is capable of receiving an electrically conductive medium and active substances contained in the electrically conductive medium and has an outlet defining an application surface adapted to receive a predetermined part of an eyeball surface, the application surface being at least partly limited by an outer line concave towards the optical axis of the eyeball, and wherein the outer wall extends from the outer line outwardly with respect to the optical axis.

2. An ocular iontophoresis device according to claim 1, wherein the outer line is a loop.

3. An ocular iontophoresis device according to claim 2, wherein the outer line is substantially a circle.

4. An ocular iontophoresis device according to claim 1, wherein the outer wall has a substantially constant inclination angle respective to the optical axis.

5. An ocular iontophoresis device according to claim 2, wherein the outer wall has a substantially constant inclination angle respective to the optical axis.

6. An ocular iontophoresis device according to claim 3, wherein the outer wall has a substantially constant inclination angle respective to the optical axis.

7. An ocular iontophoresis device according to claim 6, wherein the outer wall is tapered around the optical axis.

8. An ocular iontophoresis device according to one of claims 1 to 7, wherein:

the application surface is also delimited by an inner line,

the reservoir has an inner wall extending from the inner line, and

the hollow body is located between the inner wall and the outer wall.

9. An ocular iontophoresis device according to claim 8, wherein the inner line is concave towards the optical axis.

10. An ocular iontophoresis device according to claim 9, wherein the inner line is a loop.

11. An ocular iontophoresis device according to claim 10, wherein the inner line is substantially a circle.

12. An ocular iontophoresis device according to claim 8, wherein the inner wall extends from the inner line outwardly with respect to the optical axis of the eyeball once the ocular iontophoresis device is put on the eyeball.

13. An ocular iontophoresis device according to claim 12, wherein the inner wall has a substantially constant inclination angle respective to the optical axis.

14. An ocular iontophoresis device according to claim 13, wherein the inner wall is tapered around the optical axis.

15. An ocular iontophoresis device according to claim 9, wherein the inner wall extends from the inner line outwardly with respect to the optical axis.

16. An ocular iontophoresis device according to claim 15, wherein the outer wall has a substantially constant inclination angle with respect to the optical axis.

17. An ocular iontophoresis device according to claim 16, wherein the inner wall is tapered around the optical axis.

18. An ocular iontophoresis device according to claim 1, wherein the application surface is designed for covering at least a portion of the cornea of the eyeball.

19. An ocular iontophoresis device according to claim 1, wherein the application surface is designed for covering at least a portion of the cornea of the eyeball and at least a portion of the sclera of the eyeball.

20. An ocular iontophoresis device according to claim 1, wherein the application surface is designed for covering at least a portion of the sclera of the eyeball.

21. An ocular iontophoresis device according to claim 20, wherein the application surface is designed for covering in projection at least a portion of the ciliary body of the eyeball.

22. An ocular iontophoresis device according to claim 21, wherein the application surface is designed for covering in projection at least a portion of the anterior pars plicata ciliaris of the eyeball.

23. An ocular iontophoresis device according to claim 21, wherein the application surface is designed for covering in projection at least a portion of the posterior pars plana ciliaris of the eyeball.

24. An ocular iontophoresis device according to one of claims 21 to 23, wherein the outer wall is tapered around the optical axis with an inclination angle in the range from around 30°

to around 40°

.

25. An ocular iontophoresis device according to claim 8, wherein the inner wall is tapered around the optical axis and extends outwardly from the application surface with respect to the optical axis with a substantially constant inclination angle with respect to the optical axis of about 0°

.

26. An ocular iontophoresis device according to claim 1, wherein the reservoir comprises:

a first container for containing active substances and the electrically conductive medium; and

a second container for containing electrically conductive elements;

wherein the first and second containers are separated by a semi-permeable membrane permeable to the electrically conductive elements and non-permeable to the active substances.

27. An ocular iontophoresis device according to claim 1, wherein the outer wall of the reservoir has flexible front portions to be put on the eyeball, and wherein the outer wall of the reservoir has reinforced or rigid rear portions extending from the flexible front portions.

28. An ocular iontophoresis device according to claim 27, wherein the flexible front portions of the outer wall are progressively more rigid extending further away from the application surface.

29. An ocular iontophoresis device according to claim 28, wherein the flexible front portions of the outer wall are progressively thicker extending further away from the application surface, thereby achieving progressively-varying rigidity.

30. An ocular iontophoresis device according to one of claims 27 to 29, wherein the flexible front portions of the outer wall form a barrier to at least one of current leaking out from the reservoir and intrusion of outer contaminants into the reservoir.

31. An ocular iontophoresis device according to claim 1, wherein the reservoir contains a plurality of internal walls extending from the outer wall to define tight compartments.

32. An ocular iontophoresis device according to claim 1, further comprising at least one of:

means for filling the reservoir with the electrically conductive medium and the active substances, and

means for circulating the active substances in the reservoir.

33. An ocular iontophoresis device according to claim 1, wherein the electrically conductive medium is selected from the group consisting of an electrically conductive liquid and a gel.

34. An ocular iontophoresis device according to one of claims 21 to 23, wherein the electrically conductive medium includes active principles that are selected from the group consisting of:

beta blockers including at least one of betaxolol, levobunolol, timolol, carteolol, befunolol, or metipranolol;

alpha adrenergic agonists including at least one of brimonidine, apraclonidine, or dipivefrine;

carbonic anhydrase inhibitors including at least one of dorzololamide, brinzolamide, acetazolamide, of methazolamide;

non-specific adrenergic agonists or sympathomimetic agents including at least one of epinephrine, phenylephrine, dipevefrin, or apraclonidine;

cholinergic agonists (anticholinesterase agents) or parasympathomimetics including at least one of pilocarpine, carbachol, aceclidine, or echothiopathe; and

prostaglandin analogues including at least one of latanoprost, bimatoprost, or travoprost.

35. An ocular iontophoresis device according to claim 1, further comprising:

an active electrode associated with the reservoir so as to, when polarized, supply an electric field through the electrically conductive medium to the eyeball,

wherein the active electrode is located proximate to a bottom of the hollow body, the bottom being an opposite surface of the application surface.

36. An ocular iontophoresis device according to claim 35, wherein an area of the active electrode is greater than an area of the application surface.

37. An ocular iontophoresis device according to claim 35 or 36, wherein the active electrode has globally the same shape as the bottom of the hollow body.

38. An ocular iontophoresis device according to claim 35 or 36, wherein the active electrode includes a through opening.

39. An ocular iontophoresis device according to claim 35 or 36, wherein the active electrode is arranged, in operation, to present current density of less than 10 mA/cm² and to be polarized for around 10 minutes.

40. An ocular iontophoresis device according to claim 35 or 36, wherein the reservoir further includes an end wall which closes the bottom of the hollow body on which the active electrode is manufactured.

41. An ocular iontophoresis device according to claim 40, wherein the active electrode is formed directly on the end wall of the reservoir by a process selected from the group consisting of:

electroplating;

depositing an ink of an electrically conductive material;

depositing a solid film filled with an electrically conductive material;

overmolding polymers filled with an electrically conductive material to form conductive layers; and

depositing one wire of electrically conductive material.

42. An ocular iontophoresis device according to claim 35 or 36, wherein the active electrode is substantially parallel to the application surface.

43. An ocular iontophoresis device according to claim 35 or 36, further comprising:

a rigid rear part,

wherein the active electrode is located between the rigid rear part and the reservoir.

84. An ocular iontophoresis device according to claim 8, wherein the inner wall is tapered around the optical axis and extends outwardly from the application surface with respect to the optical axis with a substantially constant inclination angle with respect to the optical axis in the range from around 30°

to around 40°

.

44. An ocular iontophoresis device for delivering active substances to an eyeball, the ocular iontophoresis device comprising:

a reservoir; and

an active electrode,

wherein the reservoir has a hollow body capable of receiving an electrically conductive medium and active substances contained in the medium, the hollow body having a first end and a second end opposite the first end, the first end being an outlet defining an application surface intended to receive a predetermined part of an eyeball surface, and the second end defining a bottom of the reservoir,

wherein at least one wall delimiting the hollow body extends from the application surface to the bottom such that an area of the bottom is greater than an area of the application surface, and

wherein the active electrode is associated with the reservoir so as to, when polarized, supply an electric field through the electrically conductive medium to the eyeball, the active electrode extending proximate to the bottom of the reservoir and having a global area greater than the area of the application surface.

45. An ocular iontophoresis device according to claim 44, wherein:

the reservoir further comprises an outer wall at least partly delimiting the hollow body and extending between the application surface and the bottom,

the application surface is at least partly limited by an outer line concave towards the optical axis of the eyeball, and

the outer wall extends from the outer line outwardly with respect to the optical axis.

46. An ocular iontophoresis device according to claim 45, wherein the outer line is a loop.

47. An ocular iontophoresis device according to claim 46, wherein the outer line is substantially a circle.

48. An ocular iontophoresis device according to claim 46, wherein the outer wall has a substantially constant inclination angle respective to the optical axis.

49. An ocular iontophoresis device according to claim 48, wherein the outer wall is tapered around the optical axis.

50. An ocular iontophoresis device according to one of claims 45 to 49, wherein the reservoir has an inner wall extending from an inner line of the application surface, the hollow body being located between the inner wall and the outer wall.

51. An ocular iontophoresis device according to claim 50, wherein the inner line is concave towards the optical axis.

52. An ocular iontophoresis device according to claim 51, wherein the inner line is a loop.

53. An ocular iontophoresis device according to claim 52, wherein the inner line is substantially a circle.

54. An ocular iontophoresis device according to claim 51, wherein the inner wall extends from the inner line outwardly with respect to the optical axis.

55. An ocular iontophoresis device according to claim 54, wherein the inner wall has a substantially constant inclination angle respective to the optical axis.

56. An ocular iontophoresis device according to claim 55, wherein the inner wall is tapered around the optical axis.

57. An ocular iontophoresis device according to claim 44, wherein:

the reservoir has an outer wall and an inner wall at least partly delimiting the hollow body and extending between the application surface and the bottom,

the inner wall extends away from the application surface inwardly with respect to the optical axis,

and the inner wall is tapered.

58. An ocular iontophoresis device according to claim 57, wherein, from the application surface, the inner wall is closed at a determinate point or a determinate surface located between the application surface and said bottom.

59. An ocular iontophoresis device according to claim 57, wherein the inner wall contacts the bottom.

60. An ocular iontophoresis device according to one of claims 57 to 59, wherein the outer wall is substantially cylindrical.

61. An ocular iontophoresis device according to claim 44, wherein the application surface is designed for covering at least a portion of the cornea of the eye.

62. An ocular iontophoresis device according to claim 44, wherein the application surface is designed for covering at least a portion of the cornea of the eye and at least a portion of the sclera of the eye.

63. An ocular iontophoresis device according to claim 44, wherein the application surface is designed for covering at least a portion of the sclera of the eye.

64. An ocular iontophoresis device according to claim 63, wherein the application surface is designed for covering in projection at least a portion of the ciliary body of the eye.

65. An ocular iontophoresis device according to claim 64, wherein the application surface is designed for covering in projection at least a portion of the anterior pars plicata ciliaris of the eye.

66. An ocular iontophoresis device according to claim 64, wherein the application surface is designed for covering in projection at least a portion of the posterior pars plana ciliaris of the eye.

67. An ocular iontophoresis device according to one of claims 64 to 66, wherein the outer wall is tapered around the optical axis with an constant inclination angle in the range from around 30°

to around 40°

.

68. An ocular iontophoresis device according to claim 67, wherein the inner wall is tapered around the optical axis and extends inwardly with respect to the optical axis with a substantially constant inclination angle of about 0°

.

69. An ocular iontophoresis device according to claim 44, wherein the reservoir comprises:

a first container for containing the active substances and the electrically conductive medium; and

a second container for containing electrical conductive elements;

wherein the first and second containers are separated by a semi-permeable membrane permeable to the electrically conductive elements and non-permeable to the active substances.

70. An ocular iontophoresis device according to claim 44, wherein:

the at least one wall of the reservoir has front portions to be put on the eyeball which are flexible, and

the at least one wall of the reservoir has reinforced or rigid rear portions extending from the flexible front portions.

71. An ocular iontophoresis device according to claim 70, wherein the flexible front portions of the at least one wall are progressively more rigid on going progressively further away from the application surface.

72. An ocular iontophoresis device according to claim 71, wherein the flexible front portions of the at least one wall are progressively thicker extending further away from the application surface, thereby achieving progressively-varying rigidity.

73. An ocular iontophoresis device according to one of claims 70 to 72, wherein the flexible front portions of the at least one wall form a barrier to at least one of current leaking out from the reservoir and intrusion of outer contaminants into the reservoir.

74. An ocular iontophoresis device according to claim 44, wherein the reservoir contains a plurality of internal walls extending from the outer wall to define tight compartments.

75. An ocular iontophoresis device according to claim 44, further comprising at least one of:

means for filling the reservoir with the electrically conductive medium and the active substances; and

means for circulating the active substances in the reservoir.

76. An ocular iontophoresis device according to claim 44, wherein the electrically conductive medium is selected from the group consisting of an electrically conductive liquid and a gel.

77. An ocular iontophoresis device according to one of claims 64 to 66, wherein the electrically conductive medium includes active principles that are selected from the group consisting of:

beta blockers including at least one of betaxolol, levobunolol, timolol, carteolol, befunolol, or metipranolol;

alpha adrenergic agonists including at least one of brimonidine, apraclonidine, or dipivefrine;

carbonic anhydrase inhibitors including at least one of dorzololamide, brinzolamide, acetazolamide, or methazolamide;

non-specific adrenergic agonists or sympathomimetic agents including at least one of epinephrine, phenylephrine, dipevefrin, or apraclonidine;

cholinergic agonists (anticholinesterase agents) or parasympathomimetics including at least one of pilocarpine, carbachol, aceclidine, or echothiopathe; and

prostaglandin analogues including at least one of latanoprost, bimatoprost, or travoprost.

78. An ocular iontophoresis device according to claim 44, wherein the active electrode includes a through opening.

79. An ocular iontophoresis device according to claim 44, wherein the active electrode is arranged, in operation, to present current density less than 10 mA/cm² and to be polarized for around 10 minutes.

80. An ocular iontophoresis device according to claim 44, wherein the reservoir further includes an end wall which closes the bottom of the hollow body on which the active electrode is located.

81. An ocular iontophoresis device according to claim 80, wherein the active electrode is formed directly on the end wall of the reservoir by a process selected from the group consisting of:

electroplating;

depositing an ink of an electrically conductive material;

depositing a solid film filled with an electrically conductive material;

overmolding polymers filled with an electrically conductive material to form conductive layers; and

depositing one wire of electrically conductive material.

82. An ocular iontophoresis device according to one of claims 78 to 81, wherein the active electrode is substantially parallel to the application surface.

83. An ocular iontophoresis device according to claim 44, further comprising:

a rigid rear part,

wherein the active electrode is located between the rigid rear part and the reservoir.

85. An ocular iontophoresis device according to claim 67, wherein the inner wall is tapered around the optical axis and extends inwardly with respect to the optical axis with a substantially constant inclination angle in the range from around 30°

to around 40°

.