DEVICE AND METHOD FOR INTRAOCULAR DRUG DELIVERY

• US 20120078224A1
• Filed: 03/31/2011
• Published: 03/29/2012
• Est. Priority Date: 03/31/2010
• Status: Active Grant

• Current Assignee: Ocuject, LLC
• Original Assignee: Ocuject, LLC
• Inventors: Lerner, Leonid E., Shubayev, Igor
• Granted Patent: US 9,408,746 B2
• Time in Patent Office: Days
• US Class Current: 604/506
• CPC Class Codes: A61F 9/0017 implantable in, or in contact with, the eye, e.g. ocular inserts
• CPC Class Codes: A61F 9/00736 Instruments for removal of intra-ocular material or intra-ocular injection, e.g. cataract instruments A61F9/008 takes precedence
• CPC Class Codes: A61M 2005/206 With automatic needle insertion
• CPC Class Codes: A61M 2005/3267 Biased sleeves where the needle is uncovered by insertion of the needle into a patient's body
• CPC Class Codes: A61M 5/20 Automatic syringes, e.g. with automatically actuated piston rod, with automatic needle injection, filling automatically A61M5/142 , A61M5/46 take precedence; hypodermic projectiles F42B12/54
• CPC Class Codes: A61M 5/2033 Spring-loaded one-shot injectors with or without automatic needle insertion multishot dosing syringes A61M5/31525, needle insertion only A61M5/3287
• CPC Class Codes: A61M 5/204 connected to external reservoirs for multiple refilling
• CPC Class Codes: A61M 5/2053 Media being expelled from injector by pressurised fluid or vacuum for infusion A61M5/145, A61M5/155
• CPC Class Codes: A61M 5/3243 being axially-extensible, e.g. protective sleeves coaxially slidable on the syringe barrel devices for protecting guide needles in combination with catheters A61M25/0612
• CPC Class Codes: A61M 5/46 having means for controlling depth of insertion
• CPC Class Codes: A61M 5/482 Varying injection pressure, e.g. by varying speed of injection

Abstract

Devices for delivering pharmaceutical formulations into the eye are described. The devices may be integrated to include features that allow safe and atraumatic manipulation of the devices with one hand. For example, accurate placement, including proper angulation, of the device on the eye and injection of a pharmaceutical formulation into the eye can be performed using one hand. The devices may also include improved safety features. For example, the devices may include an actuation mechanism that controls the rate and depth of injection into the eye. Some devices include a dynamic resistance component capable of adjusting the amount of pressure applied to the eye surface. Related methods and systems comprising the devices are also described.

Claims

1. An integrated device for intraocular drug delivery comprising:

a housing sized and shaped for manipulation with one hand, the housing having a proximal end and a distal end;

an ocular contact surface at the housing distal end;

a measuring component;

a conduit at least partially within the housing, the conduit having a proximal end, a distal end, and a lumen extending therethrough;

an actuation mechanism contained within the housing and operably connected to the conduit and a reservoir for holding an active agent;

a trigger coupled to the housing and configured to activate the actuation mechanism; and

a dynamic resistance component coupled to the housing.

2. The integrated device of claim 1, wherein the dynamic resistance component comprises a slidable element coupled to the housing.

3. The integrated device of claim 2, wherein the slidable element comprises a dynamic sleeve having a proximal end, a distal end, and an inner surface.

4. The integrated device of claim 3, wherein the proximal end and the distal end of the dynamic sleeve are tapered.

5. The integrated device of claim 4, wherein the tapered dynamic sleeve and the housing generate a force between 0 N and about 2 N.

6. The integrated device of claim 4, wherein the tapered dynamic sleeve and the housing generate a force between about 0.1 N and about 1 N.

7. The integrated device of claim 3, wherein the inner surface of the dynamic sleeve comprises one or more high-traction surfaces.

8. The integrated device of claim 7, wherein the housing comprises one or more high-traction surfaces.

9. The integrated device of claim 8, wherein the one or more high-traction surfaces of the dynamic sleeve and the housing generate a force between 0 N and about 2 N.

10. The integrated device of claim 8, wherein the one or more high-traction surfaces of the dynamic sleeve and the housing generate a force between about 0.1 N and about 1.0 N.

11. The integrated device of claim 3, wherein the dynamic sleeve further comprises a fine sleeve mobility control component.

12. The integrated device of claim 1, wherein the ocular contact surface comprises a ring, a flange, or a combination thereof.

13. The integrated device of claim 12, wherein the ocular contact surface comprises a ring.

14. The integrated device of claim 13, wherein the ring has a diameter between about 0.3 mm and about 8 mm.

15. The integrated device of claim 1, wherein the ocular contact surface is flat, convex, or concave.

16. The integrated device of claim 1, wherein the ocular contact surface comprises one or more traction elements.

17. The integrated device of claim 1, wherein the ocular contact surface comprises an adhesive component.

18. The integrated device of claim 17, wherein the adhesive component comprises a suction mechanism.

19. The integrated device of claim 1, wherein the ocular contact surface comprises a material selected from the group consisting of nylon fiber, cotton fiber, hydrogel, spongiform material, styrofoam, other foams, silicone, plastic, polypropylene, polyethylene, polytetrafluoroethylene, and combinations thereof.

20. The integrated device of claim 1, wherein the actuation mechanism comprises a manual actuation mechanism.

21. The integrated device of claim 20, wherein the manual actuation mechanism comprises a control lever for slidable advancement of a plunger.

22. The integrated device of claim 1, wherein the actuation mechanism comprises an automated actuation mechanism.

23. The integrated device of claim 22, wherein the automated actuation mechanism comprises a spring-loaded actuation mechanism.

24. The integrated device of claim 23, wherein the spring-loaded actuation mechanism is configured to deliver the active agent into the intraocular space at a rate ranging from about 1 μ

l/sec to about 1 ml/sec.

25. The integrated device of claim 24, wherein the spring-loaded actuation mechanism delivers the active agent into the intraocular space at a rate ranging from about 10 μ

l/sec to about 100 μ

l/sec.

26. The integrated device of claim 23, wherein the spring-loaded actuation mechanism generates a force of about 0.1 N to about 1.0 N.

27. The integrated device of claim 23, wherein the spring-loaded actuation mechanism comprises a first spring and a second spring.

28. The integrated device of claim 27, wherein the second spring is configured to deploy a plunger and to control the rate of delivery of the active agent.

29. The integrated device of claim 27, wherein the first spring is configured to move the conduit from a first non-deployed state to a second deployed state and control the rate and force of deployment of the conduit.

30. The integrated device of claim 1, wherein the actuation mechanism is a partially automated actuation mechanism.

31. The integrated device of claim 30, wherein the partially automated actuation mechanism comprises a control lever for slidable advancement of a plunger.

32. The integrated device of claim 30, wherein the partially automated actuation mechanism comprises a spring-loaded actuation mechanism.

33. The integrated device of claim 32, wherein the spring-loaded actuation mechanism is configured to deliver the active agent into the intraocular space at a rate ranging from about 1 μ

l/sec to about 1 ml/sec.

34. The integrated device of claim 32, wherein the spring-loaded actuation mechanism delivers the active agent into the intraocular space at a rate ranging from about 10 μ

l/sec to about 100 μ

l/sec.

35. The integrated device of claim 32, wherein the spring-loaded actuation mechanism generates a force of about 0.1 N to about 1.0 N.

36. The integrated device of claim 32, wherein the spring-loaded actuation mechanism comprises a first spring and a second spring.

37. The integrated device of claim 36, wherein the second spring is configured to deploy a plunger and to control the rate of delivery of the active agent.

38. The integrated device of claim 36, wherein the first spring is configured to move the conduit from a first non-deployed state to a second deployed state and control the rate and force of deployment of the conduit.

39. The integrated device of claim 1, wherein the actuation mechanism is a pneumatic actuation mechanism.

40. The integrated device of claim 1, wherein the active agent is selected from the group consisting of steroidal anti-inflammatories, nonsteroidal anti-inflammatories, anti-infectives, anti-allergens, cholinergic antagonists and agonists, adrenergic antagonists and agonists, anti-glaucoma agents, neuroprotection agents, agents for cataract prevention or treatment, anti-proliferatives, anti-tumor agents, complement inhibitors, vitamins, growth factors, agents to inhibit growth factors, gene therapy vectors, chemotherapy agents, protein kinase inhibitors, small interfering RNAs, analogs, derivatives, and modifications thereof, and combinations thereof.

41. The integrated device of claim 1, wherein the active agent is selected from the group consisting of ranibizumab, bevacizumab, pegaptanib, dexamethasone, dexamethasone sodium phosphate, triamcinolone, triamcinolone acetonide, fluocinolone, taxol-like drugs, aflibercept, anecortave acetate, and limus family compounds.

42. The integrated device of claim 36, wherein the limus family compounds are selected from the group consisting of sirolimus, SDZ-RAD, tacrolimus, everolimus, pimecrolimus, zotarolimus, CCI-779, AP23841, and ABT-578, analogs, derivatives, conjugates, salts, and modifications thereof, and combinations thereof.

43. The integrated device of claim 1, wherein the reservoir is made from a cyclic olefin series resin.

44. The integrated device of claim 40, wherein the reservoir lacks silicone oil or one of its derivatives.

45. The integrated device of claim 1, wherein the measuring component is attached to the ocular contact surface.

46. The integrated device of claim 1, wherein the measuring component comprises one or more radially extending members.

47. The integrated device of claim 46, wherein the one or more radially extending members comprises a raised distal tip.

48. The integrated device of claim 46, wherein the one or more radially extending members is flexible.

49. The integrated device of claim 48, wherein the measuring component comprises a positional indicator component.

50. The integrated device of claim 1, wherein the reservoir is preloaded with the active agent.

51. The integrated device of claim 3, wherein one of the proximal end and distal end of the dynamic sleeve is tapered.

52. A method for intraocular drug delivery comprising:

positioning an ocular contact surface of an integrated device on the surface of an eye using a measuring component to determine the location of an injection site, the integrated device further comprising a housing, a dispensing member a dynamic resistance component, a reservoir for holding an active agent, and an actuation mechanism;

applying pressure against the surface of the eye at a target injection site using the dynamic resistance component; and

delivering an active agent from the reservoir into the eye by activating the actuation mechanism,

wherein the steps of positioning, applying, and delivering are completed with one hand.

53. The method of claim 52, wherein the injection site is between about 1 mm anterior to the limbus and about 6 mm posterior to the limbus.

54. The method of claim 52, wherein the injection site is between about 3 mm to about 4 mm posterior to the limbus.

55. The method of claim 52, wherein the active agent is preloaded in the reservoir.

56. The method of claim 52, wherein the active agent is loaded into the reservoir using a drug loading mechanism.

57. The method of claim 52, wherein the active agent is selected from the group consisting of steroidal anti-inflammatories, nonsteroidal anti-inflammatories, anti-infectives, anti-allergens, cholinergic antagonists and agonists, adrenergic antagonists and agonists, anti-glaucoma agents, neuroprotection agents, agents for cataract prevention or treatment, anti-proliferatives, anti-tumor agents, complement inhibitors, vitamins, growth factors, agents to inhibit growth factors, gene therapy vectors, chemotherapy agents, protein kinase inhibitors, small interfering RNAs, analogs, derivatives, conjugates, and modifications thereof, and combinations thereof.

58. The method of claim 52, wherein the active agent is selected from the group consisting of ranibizumab, bevacizumab, pegaptanib, dexamethasone, dexamethasone sodium phosphate, triamcinolone, triamcinolone acetonide, fluocinolone, taxol-like drugs, aflibercept, anecortave acetate, and limus family compounds.

59. The method of claim 58, wherein the limus family compounds are selected from the group consisting of sirolimus, SDZ-RAD, tacrolimus, everolimus, pimecrolimus, zotarolimus, CCI-779, AP23841, and ABT-578, analogs, derivatives, conjugates, salts, and modifications thereof, and combinations thereof.

60. The method of claim 52, wherein the active agent is used to treat an ocular condition selected from the group consisting of macular edema, cystoid macular edema, diabetic macular edema, post-operative macular edema, retinal edema, age-related macular degeneration, BRVO, CRVO, uveitis, and central serous chorioretinopathy.

61. The method of claim 52, wherein the actuation mechanism delivers the active agent into the intraocular space at a rate ranging from about 1 μ

l/sec to about 1 ml/sec.

62. The method of claim 52, wherein the actuation mechanism delivers the active agent into the intraocular space at a rate ranging from about 5 μ

l/sec to about 200 μ

l/sec.

63. The method of claim 52, wherein the actuation mechanism delivers the active agent into the intraocular space at a rate ranging from about 10 μ

l/sec to about 100 μ

l/sec.

64. The method of claim 52, wherein the actuation mechanism generates a force of about 0.1 N to about 1.0 N.

65. The method of claim 52, wherein the dynamic resistance component comprises a slidable element coupled to the housing of the integrated device.

66. The method of claim 65, wherein the slidable element comprises a dynamic sleeve having a tapered proximal end and a tapered distal end.

67. The method of claim 65, wherein the step of applying pressure against the surface of the eye retracts the slidable element to expose the dispensing member.

68. The method of claim 67, further comprising the step of manual actuation of a plunger to deliver the active agent.

69. The method of claim 52, wherein the step of applying pressure against the surface of the eye comprises slidable advancement of the dynamic resistance component.

70. The method of claim 69, wherein slidable advancement of the dynamic sleeve generates a force between itself and the housing ranging from 0 N to about 2 N.

71. The method of claim 69, wherein slidable advancement of the dynamic sleeve generates a force between itself and the housing ranging from about 0.1 N to about 1 N.

72. The method of claim 69, wherein the slidable advancement is manually adjustable.

73. The method of claim 69, wherein the slidable advancement is automatically adjustable.

74. The method of claim 52, wherein the dynamic resistance component comprises an ocular wall tension control mechanism.

75. An integrated device for intraocular drug delivery comprising:

a housing sized and shaped for manipulation with one hand, the housing having a proximal end and a distal end;

an ocular contact surface at the housing distal end;

a measuring component;

a conduit at least partially within the housing, the conduit having a proximal end, a distal end, and a lumen extending therethrough;

an actuation mechanism contained within the housing and operably connected to the conduit and a reservoir for holding an active agent;

a trigger coupled to the housing and configured to activate the actuation mechanism; and

an ocular wall tension control mechanism coupled to the housing.

76. The integrated device of claim 75, wherein the ocular wall tension control mechanism comprises a slidable cap having a locking mechanism.

77. The integrated device of claim 76, wherein the locking mechanism is a manually operated.

78. The integrated device of claim 76, wherein the locking mechanism is an automatically operated mechanism.

79. The integrated device of claim 76, wherein the locking mechanism comprises a locking pin.

80. The integrated device of claim 76, wherein the slidable cap comprises one or more high traction surfaces.

81. The integrated device of claim 80, wherein the one or more high traction surfaces comprise ridges on an inner surface of the slidable cap.

82. The integrated device of claim 75, wherein the ocular wall tension control mechanism comprises a pressure sensor.

83. The integrated device of claim 75, wherein the ocular wall tension control mechanism comprises a pressure accumulator.

84. A method for intraocular drug delivery comprising:

positioning an ocular contact surface of an integrated device on the surface of an eye using a measuring component to determine the location of an injection site, the integrated device further comprising a housing, a dispensing member an ocular wall tension control component, a reservoir for holding an active agent, and an actuation mechanism;

applying pressure against the surface of the eye at a target injection site using the ocular wall tension control component; and

delivering an active agent from the reservoir into the eye by activating the actuation mechanism,

wherein the steps of positioning, applying, and delivering are completed with one hand.

85. The method of claim 84, wherein the step of applying pressure against the surface of the eye comprises slidable advancement of the ocular wall tension control component.

86. The method of claim 85, wherein slidable advancement of the ocular wall tension control mechanism generates a force between itself and the housing ranging from 0 N to about 2 N.

87. The method of claim 85, wherein slidable advancement of the ocular wall tension control component generates a force between itself and the housing ranging from about 0.1 N to about 1 N.

88. An injection device for intraocular drug delivery comprising:

a housing sized and shaped for manipulation with one hand, the housing having a proximal end and a distal end;

an ocular contact surface at the housing distal end;

a conduit at least partially within the housing, the conduit having a proximal end, a distal end, and a lumen extending therethrough;

an actuation mechanism contained within the housing and operably connected to the conduit and a reservoir for holding an active agent;

a trigger coupled to the housing and configured to activate the actuation mechanism; and

a dynamic resistance component.

89. The injection device of claim 88, wherein the dynamic resistance component comprises a dynamic sleeve having a proximal end, a distal end, and an inner surface.

90. The injection device of claim 89, wherein the proximal end and the distal end of the dynamic sleeve are tapered.

91. The injection device of claim 89, wherein one of the proximal end and the distal end of the dynamic sleeve is tapered.

92. The injection device of claim 89, wherein the inner surface of the dynamic sleeve comprises ridges.

93. The injection device of claim 88, wherein the dynamic sleeve further comprises a fine sleeve mobility control component.

94. The injection device of claim 88, wherein the device further comprises a measuring component.