Cutaneous administration system

• US 6,723,077 B2
• Filed: 09/28/2001
• Issued: 04/20/2004
• Est. Priority Date: 09/28/2001
• Status: Expired due to Term

• Current Assignee: Hewlett-Packard Development Company, L.P. (HP Inc.)
• Original Assignee: Hewlett-Packard Development Company, L.P. (HP Inc.)
• Inventors: Lo, Clement C., Pickup, Ray L., Noonan, William D.
• Primary Examiner(s): Lo, Weilun
• Assistant Examiner(s): TRUONG, LINH T
• Application Number:
  US09/967,603
• Publication Number:
  US 20030065294A1
• Time in Patent Office: 935 Days
• Field of Search: 604/305-308, 604/310, 604/19-20, 128/204.24, 128/200.22, 128/200.14, 424/446-449, 239/102.2
• US Class Current: 604/305
• CPC Class Codes: A01K 11/005 Branding or tattooing devices for animals
• CPC Class Codes: A01K 13/003 Devices for applying insecticides or medication A01K27/007 takes precedence; for veterinary purposes A61D7/00
• CPC Class Codes: A61M 31/002 Devices for releasing a drug at a continuous and controlled rate for a prolonged period of time artificial gland structures or devices A61F2/022; intra-uterine contraceptive devices A61F6/14; tampons for introducing into the vagina A61F13/20, A61L15/00; suppositories or bougies for intra-vaginal or intra-uterine application A61K9/02; physical forms of medicinal preparations for sustained or differential drug release A61K9/20, A61K9/50
• CPC Class Codes: A61M 35/003 Portable hand-held applicators having means for dispensing or spreading integral media hand-held massage devices with liquid delivery A61H7/003
• CPC Class Codes: A61M 37/00 Other apparatus for introducing media into the body for reproduction or fertilisation A61B17/425; apparatus for iontophoresis or cataphoresis A61N1/30; Percutany, i.e. introducing medicines into the body by diffusion through the skin salt baths A61H33/04
• CPC Class Codes: A61M 37/0084 Tattooing apparatus with incorporated liquid feeding device
• CPC Class Codes: A61M 5/14248 of the skin patch type
• CPC Class Codes: B41J 2/16505 Caps, spittoons or covers for cleaning or preventing drying out
• CPC Class Codes: B41J 2/16535 using wiping constructions B41J2/16552 takes precedence
• CPC Class Codes: B41J 3/36 for portability , i.e. hand-held printers or laptop printers B41J3/4075 takes precedence
• CPC Class Codes: B41J 3/407 for marking on special material

Abstract

Bioactive agents are cutaneously delivered by a jet dispenser using inkjet technology, such as that used in printing. The dispenser propels precise volumes of bioactive agent toward the skin, where they exert a local or topical effect, or move through the skin for transdermal systemic delivery. Drugs are either delivered directly to the skin, or are introduced into a transdermal patch, which may receive repeated dosages. A controller in the dispenser may control delivery of multiple different drugs, timing of drug administration, or change drug regimens in response to a changing medical condition of a patient, such as those monitored by a sensor in communication with the controller, for example to prevent an overdose. The dispenser may act as an electromechanical patch, capable of long term administration of drugs to the skin, to achieve local or systemic pharmaceutical effects. Administration methods are also provided, along with replacement kits.

Claims

1. An applicator for cutaneous delivery of a bioactive composition to a cutaneous target, comprising:

a jet dispenser comprising an orifice, and a container which holds and delivers the bioactive composition to said orifice for ejection therethrough;

a spacer positioned between the dispenser orifice and the target during ejection of the bioactive composition to the target;

a main body which supports said container; and

a dispensing head which supports said orifice;

wherein said dispensing head supports plural orifices each fluidically coupled to said container.

2. An applicator according to claim 1, wherein the spacer is supported by the dispenser.

3. An applicator according to claim 1, wherein the spacer is for attachment to the cutaneous target.

4. An applicator according to claim 1, further comprising an adhesive applicator patch for application to the cutaneous target.

5. An applicator according to claim 1, wherein the applicator is an applicator for transdermal delivery of a bioactive composition capable of transdermal flux.

6. An applicator according to claim 1, further comprising a bioactive composition in the container.

7. An applicator according to claim 6, wherein the bioactive composition is a pharmaceutical composition.

8. An applicator according to claim 7, wherein the pharmaceutical composition is capable of transdermal delivery.

9. An applicator according to claim 1, wherein the dispenser is a thermal droplet jet dispenser.

10. An applicator according to claim 1, wherein the dispenser is a piezoelectric droplet jet dispenser.

11. An applicator according to claim 1, further comprising a controller which automatically ejects the bioactive composition from the dispenser orifice at selected times.

12. An applicator according to claim 11, wherein the controller is a microprocessor programmed to dispense the bioactive composition at predetermined intervals.

13. An applicator according to claim 1, wherein the container comprises multiple container modules.

14. An applicator according to claim 13, wherein the multiple container modules are removable from the dispenser.

15. An applicator according to claim 13, wherein at least two of the container modules contain a bioactive substance.

16. An applicator according to claim 15, wherein at least one of the container modules contains a bioactive agent in powder form.

17. An applicator according to claim 15, wherein at least two of the container modules contain different bioactive substances that combine after ejection to produce a bioactive effect.

18. An applicator according to claim 17, wherein at least one of the bioactive substances is a penetration enhancer that improves cutaneous penetration of another bioactive substance.

19. An applicator according to claim 18, wherein the penetration enhancer is dimethyl sulfoxide (DMSO).

20. An applicator according to claim 15, wherein the bioactive composition is a nitrate, an anti-hypertensive drug, an analgesic, a hormone or an analogue thereof, or nicotine or an analogue thereof.

21. An applicator according to claim 20, wherein:

the dispenser is a piezoelectric droplet jet dispenser; and

the nitrate is nitroglycerin.

22. An applicator according to claim 20, wherein the anti-hypertensive drug is clonidine or minoxidil, the analgesic is fentanyl, or the hormone is estrogen or testosterone.

23. An applicator according to claim 1, further comprising an attachment member for selectively retaining the dispenser in prolonged contact with the cutaneous target.

24. An applicator according to claim 23, wherein the attachment member comprises a strap.

25. An applicator according to claim 23, wherein the attachment member comprises an adhesive.

26. An applicator according to claim 1, wherein:

the spacer comprises a sealing member that for selectively substantially sealing the dispenser against the skin of a subject to form a substantially closed chamber when the dispenser is in contact with the skin.

27. An applicator according to claim 26, wherein the sealing member is a continuous elastomeric seal.

28. An applicator according to claim 1, further comprising an indicator which indicates a degree of depletion of the bioactive composition in the dispenser.

29. An applicator according to claim 1 further comprising:

a bio-sensor which monitors a measurable parameter of a subject and generates a signal in response thereto; and

a controller which automatically dispenses the bioactive composition from the dispenser orifice in response to said signal.

30. An applicator according to claim 29 wherein the bio-sensor comprises a pulse oximetry device.

31. An applicator according to claim 30 wherein said parameter comprises pulse rate.

32. An applicator according to claim 30 wherein said parameter comprises blood oxygenation levels.

33. An applicator according to claim 30 wherein said bio-sensor communicates said signal to the controller by infrared communication.

34. An applicator according to claim 30 wherein said bio-sensor communicates said signal to the controller by radiowave communication.

35. An applicator according to claim 1, further comprising a display which displays information about said composition.

36. An applicator according to claim 1, further comprising an interface which receives a memory storage device containing dosage information concerning administration of said composition.

37. An applicator according to claim 1, further comprising a keypad input which receives dosage information concerning administration of said composition.

38. An applicator according to claim 1, further comprising:

a display which displays information about said composition, including various dosages; and

a keypad input including scroll keys which when activated cause the display to selectively show said various dosages.

39. An applicator according to claim 1, further comprising a controller which is programmable.

40. An applicator according to claim 39 wherein said controller is programmable from a remote computer in communication with said controller.

41. An applicator according to claim 1, further comprising a flexible link which couples together said main body and said dispensing head.

42. An applicator according to claim 41, wherein said flexible link is hollow and contains a fluid conduit which fluidically couples said container to said orifice.

43. An applicator according to claim 1, further comprising a main body which supports said container and said orifice.

44. An applicator according to claim 43, wherein said container is removable from the main body.

45. An applicator according to claim 1, further comprising a sensor.

46. An applicator according to claim 45, further comprising a controller in communication with said sensor.

47. An applicator according to claim 46, wherein:

said sensor comprises an optical sensor;

said target changes color following delivery of the bioactive composition; and

said optical sensor detects said color change and in response thereto, the controller ceases ejection of said composition.

48. An applicator according to claim 46, wherein:

said sensor comprises an optical sensor;

said target changes color following absorption of the bioactive composition; and

said optical sensor detects said color change and in response thereto, the controller causes said orifice to eject said composition.

49. An applicator according to claim 46, wherein:

said sensor comprises an optical sensor;

the container comprises two container modules each containing different bioactive substances;

the target has indicia detectable by said optical sensor indicative of one of said different bioactive substances; and

the controller causes said orifice to eject said one of said different bioactive substances.

50. An applicator according to claim 1, further comprising a dermal patch between said orifice and said target.

52. An applicator according to claim 1, wherein the dispenser comprises a silicon electrostatic actuated droplet jet dispenser.

53. An applicator according to claim 28, wherein said indicator comprises an indicator light.

54. An applicator according to claim 28, wherein said indicator comprises an audible signal.

55. An applicator according to claim 28, wherein said indicator comprises a tactile signal.

56. An applicator according to claim 55, wherein said tactile signal comprises a vibratory signal.

57. An applicator according to claim 45, wherein said sensor comprises an optical sensor.

58. An applicator according to claim 45, wherein said sensor comprises a mechanical sensor which monitors a physical parameter of a subject.

59. An applicator according to claim 58, wherein said mechanical sensor comprises an accelerometer.

60. An applicator according to claim 59, wherein said accelerometer monitors activity of a subject bearing said cutaneous target and adjusts said delivery in response to said monitoring.

61. An applicator according to claim 1, further including an activation device which may be manually triggered to eject said bioactive composition from the jet dispenser.

62. An applicator according to claim 61, further including plural activation devices each bearing a label corresponding to an event, with different dosages of the bioactive composition being ejected from the jet dispenser according to which of the plural activation devices is triggered.

63. An applicator according to claim 61, wherein the jet dispenser contains plural bioactive compositions, and the applicator further includes plural activation devices with different bioactive compositions being ejected from the jet dispenser according to which of the plural activation devices is triggered.

64. An applicator according to claim 1, further including a reservoir containing said bioactive composition and a fluid conduit to convey the bioactive composition from the reservoir to the jet dispenser.

65. An applicator according to claim 64, wherein said fluid conduit comprises tubing.

66. An applicator according to claim 64, wherein said reservoir comprises a collapsible bladder.

51. An applicator according to claim wherein the dermal patch is of an absorbent material which receives said delivery of said composition.

67. An applicator for cutaneous delivery of a bioactive composition to a cutaneous target, comprising:

a jet dispenser comprising an orifice, and a container which holds and delivers the bioactive composition to said orifice for ejection therethrough; and

a spacer positioned between the dispenser orifice and the target during ejection of the bioactive composition to the target;

wherein the container comprises multiple container modules and at least two of the container modules contain a bioactive substance, the at least two of the container modules containing different bioactive substances that combine after ejection to produce a bioactive effect.

68. An applicator according to claim 67, wherein at least one of the bioactive substances is a penetration enhancer that improves cutaneous penetration of another bioactive substance.

69. An applicator according to claim 68, therein the penetration enhancer is dimethyl sulfoxide (DMSO).

70. An applicator for cutaneous delivery of a bioactive composition to a cutaneous target, comprising:

a jet dispenser comprising an orifice, and a container which holds and delivers the bioactive composition to said orifice for ejection therethrough; and

a spacer positioned between the dispenser orifice and the target during ejection of the bioactive composition to the target;

wherein the container comprises multiple container modules and at least two of the container modules contain a bioactive substance;

wherein the bioactive composition is a nitrate, an anti-hypertensive drug, an analgesic, a hormone or an analogue thereof, or nicotine or an analogue thereof;

wherein the dispenser is a piezoelectric droplet jet dispenser and the nitrate is nitroglycerin.

71. An applicator for cutaneous delivery of a bioactive composition to a cutaneous target, comprising:

a jet dispenser comprising an orifice, and a container which holds and delivers the bioactive composition to said orifice for ejection therethrough; and

a spacer positioned between the dispenser orifice and the target during ejection of the bioactive composition to the target;

wherein the container comprises multiple container modules and at least two of the container modules contain a bioactive substance;

wherein the bioactive composition is a nitrate, an anti-hypertensive drug, an analgesic, a hormone or an analogue thereof, or nicotine or an analogue thereof;

wherein the anti-hypertensive drug is clonidine or minoxidil, the analgesic is fentanyl, or the hormone is estrogen or testosterone.

72. An applicator for cutaneous delivery of a bioactive composition to a cutaneous target, comprising:

a jet dispenser comprising an orifice, and a container which holds and delivers the bioactive composition to said orifice for ejection therethrough;

a spacer positioned between the dispenser orifice and the target during ejection of the bioactive composition to the target; and

an attachment member for selectively retaining the dispenser in prolonged contact with the cutaneous target;

wherein the attachment member comprises an adhesive.

73. An applicator for cutaneous delivery of a bioactive composition to a cutaneous target, comprising:

a jet dispenser comprising an orifice, and a container which holds and delivers the bioactive composition to said orifice for ejection therethrough; and

a spacer positioned between the dispenser orifice and the target during ejection of the bioactive composition to the target;

wherein the spacer comprises a sealing member that selectively substantially seals the dispenser against skin of a subject to form a substantially closed chamber when the dispenser is in contact with the skin;

wherein the sealing member is a continuous elastomeric seal.

74. An applicator for cutaneous delivery of a bioactive composition to a cutaneous target comprising skin covering a subject having a measurable parameter, the applicator comprising:

a jet dispenser comprising an orifice, and a container which holds and delivers the bioactive composition to said orifice for ejection therethrough;

a spacer positioned between the dispenser orifice and the target during ejection of the bioactive composition to the target;

a bio-sensor which monitors said parameter of the subject and generates a signal in response thereto; and

a controller which automatically dispenses the bioactive composition from the dispenser orifice in response to said signal;

wherein the bio-sensor comprises a pulse oximetry device.

75. An applicator according to claim 74 wherein said parameter comprises pulse rate.

76. An applicator according to claim 74 wherein said parameter comprises blood oxygenation levels.

77. An applicator according to claim 74 wherein said bio-sensor communicates said signal to the controller by infrared communication.

78. An applicator according to claim 74 wherein said bio-sensor communicates said signal to the controller by radiowave communication.

79. An applicator for cutaneous delivery of a bioactive composition to a cutaneous target, comprising:

a jet dispenser comprising an orifice, and a container which holds and delivers the bioactive composition to said orifice for ejection therethrough;

a spacer positioned between the dispenser orifice and the target during ejection of the bioactive composition to the target; and

a controller which is programmable, wherein said controller is programmable from a remote computer in communication with said controller.

80. An applicator for cutaneous delivery of a bioactive composition to a cutaneous target, comprising:

a jet dispenser comprising an orifice, and a container which holds and delivers the bioactive composition to said orifice for ejection therethrough;

a spacer positioned between the dispenser orifice and the target during ejection of the bioactive composition to the target;

a main body which supports said container;

a dispensing head which supports said orifice; and

a flexible link which couples together said main body and said dispensing head.

81. An applicator according to claim 80, wherein said flexible link is hollow and contains a fluid conduit which fluidically couples said container to said orifice.

82. An applicator for cutaneous delivery of a bio active composition to a cutaneous target, comprising:

a jet dispenser comprising an orifice, and a container which holds and delivers the bioactive composition to said orifice for ejection therethrough;

a spacer positioned between the dispenser orifice and the target during ejection of the bioactive composition to the target;

a sensor; and

a controller in communication with said sensor;

wherein said sensor comprises an optical sensor, said target changes color following delivery of the bioactive composition, and said optical sensor detects said color change and in response thereto, the controller ceases ejection of said composition.

83. An applicator for cutaneous delivery of a bioactive composition to a cutaneous target, comprising:

a jet dispenser comprising an orifice, and a container which holds and delivers the bioactive composition to said orifice for ejection therethrough;

a spacer positioned between the dispenser orifice and the target during ejection of the bioactive composition to the target;

a sensor; and

a controller in communication with said sensor;

wherein said sensor comprises an optical sensor, said target changes color following absorption of the bioactive composition, and said optical sensor detects said color change and in response thereto, the controller causes said orifice to eject said composition.

84. An applicator for cutaneous delivery of a bioactive composition to a cutaneous target, comprising:

a jet dispenser comprising an orifice, and a container which holds and delivers the bioactive composition to said orifice for ejection therethrough;

a spacer positioned between the dispenser orifice and the target during ejection of the bioactive composition to the target;

a sensor; and

a controller in communication with said sensor;

wherein said sensor comprises an optical sensor, the container comprises two container modules each containing different bioactive substances, the target has indicia detectable by said optical sensor indicative of one of said different bioactive substances, and the controller causes said orifice to eject said one of said different bioactive substances.

85. An applicator for cutaneous delivery of a bio active composition to a cutaneous target, comprising:

a jet dispenser comprising an orifice, and a container which holds and delivers the bioactive composition to said orifice for ejection therethrough; and

a spacer positioned between the dispenser orifice and the target during ejection of the bioactive composition to the target;

wherein the dispenser comprises a silicon electrostatic actuated droplet jet dispenser.

86. An applicator for cutaneous delivery of a bioactive composition to a cutaneous target, comprising:

a jet dispenser comprising an orifice, and a container which holds and delivers the bioactive composition to said orifice for ejection therethrough;

a spacer positioned between the dispenser orifice and the target during ejection of the bioactive composition to the target; and

an indicator which indicates a degree of completion of the bioactive composition in the dispenser;

wherein said indicator comprises an indicator light.

87. An applicator for cutaneous delivery of a bioactive composition to a cutaneous target, comprising:

a jet dispenser comprising an orifice, and a container which holds and delivers the bioactive composition to said orifice for ejection therethrough;

a spacer positioned between the dispenser orifice and the target during ejection of the bioactive composition to the target; and

an indicator which indicates a degree of completion of the bioactive composition in the dispenser;

wherein said indicator comprises an audible signal.

88. An applicator for cutaneous delivery of a bioactive composition to a cutaneous target, comprising:

a jet dispenser comprising an orifice, and a container which holds and delivers the bioactive composition to said orifice for ejection therethrough;

a spacer positioned between the dispenser orifice and the target during ejection of the bioactive composition to the target; and

an indicator which indicates a degree of completion of the bioactive composition in the dispenser;

wherein said indicator comprises a tactile signal.

89. An applicator according to claim 88, wherein said tactile signal comprises a vibratory signal.

90. An applicator for cutaneous delivery of a bioactive composition to a cutaneous target, comprising:

a jet dispenser comprising an orifice, and a container which holds and delivers the bioactive composition to said orifice for ejection therethrough;

a spacer positioned between the dispenser orifice and the target during ejection of the bioactive composition to the target; and

an optical sensor.

91. An applicator for cutaneous delivery of a bioactive composition to a cutaneous target, comprising:

a jet dispenser comprising an orifice, and a container which holds and delivers the bioactive composition to said orifice for ejection therethrough;

a spacer positioned between the dispenser orifice and the target during ejection of the bioactive composition to the target; and

a mechanical sensor which monitors a physical parameter of a subject.

92. An applicator according to claim 91, said mechanical sensor comprises an accelerometer.

93. An applicator according to claim 92, wherein said accelerometer monitors activity of a subject bearing said cutaneous target and adjusts said delivery in response to said monitoring.

94. An applicator for cutaneous delivery of a bioactive composition to a cutaneous target, comprising:

a jet dispenser comprising an orifice, and a container which holds and delivers the bioactive composition to said orifice for ejection therethrough;

a spacer positioned between the dispenser orifice and the target during ejection of the bioactive composition to the target; and

a plurality of activation devices which may be manually triggered to eject said bioactive composition from the jet dispenser, each activation device bearing a label corresponding to an event, with different dosages of the bioactive composition being ejected from the jet dispenser according to which of the plural activation devices is triggered.

95. An applicator for cutaneous delivery of a bioactive composition to a cutaneous target, comprising:

a jet dispenser comprising an orifice, and a container which holds and delivers the bioactive composition to said orifice for ejection therethrough;

a spacer positioned between the dispenser orifice and the target during ejection of the bioactive composition to the target; and

an activation device which may be manually triggered to eject said bioactive composition from the jet dispenser;

wherein the jet dispenser contains plural bioactive compositions, and the applicator further includes plural activation devices with different bioactive compositions being ejected from the jet dispenser according to which of the plural activation devices is triggered.

96. An applicator for cutaneous delivery of a bioactive composition to a cutaneous target, comprising:

a jet dispenser comprising an orifice, and a container which holds and delivers the bioactive composition to said orifice for ejection therethrough;

a spacer positioned between the dispenser orifice and the target during ejection of the bioactive composition to the target; and

a reservoir containing said bioactive composition and a fluid conduit to convey the bio active composition from the reservoir to the jet dispenser, wherein said fluid conduit comprises tubing.

97. An applicator for cutaneous delivery of a bioactive composition to a cutaneous target, comprising:

a jet dispenser comprising an orifice, and a container which holds and delivers the bioactive composition to said orifice for ejection therethrough;

a spacer positioned between the dispenser orifice and the target during ejection of the bioactive composition to the target; and

a reservoir containing said bioactive composition and a fluid conduit to convey the bioactive composition from the reservoir to the jet dispenser, wherein said reservoir comprises a collapsible bladder.