Transdermal perfusion of fluids

• US 6,048,337 A
• Filed: 12/06/1994
• Issued: 04/11/2000
• Est. Priority Date: 01/07/1992
• Status: Expired due to Fees

• Current Assignee: Principal AB
• Original Assignee: Principal AB
• Inventors: Svedman, Pal
• Primary Examiner(s): Stright, Ronald
• Assistant Examiner(s): Cho, David J.
• Application Number:
  US08/350,488
• Time in Patent Office: 1,953 Days
• Field of Search: 604/289, 604/290, 604/305, 604/311, 604/313, 604/315, 604/316, 424/447-449, 128/573, 128/578, 128/579
• US Class Current: 604/313
• CPC Class Codes: A61B 10/0035 Vaccination diagnosis other than by injuring the skin, e.g. allergy test patches
• CPC Class Codes: A61B 17/20 for vaccinating or cleaning the skin previous to the vaccination diagnosis by vaccination other than by injuring the skin A61B10/0035 ; apparatus for injections A61M
• CPC Class Codes: A61B 17/205 Vaccinating by means of needles or other puncturing devices
• 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

Abstract

A housing is secured to an area of skin to allow suction to be applied to a local area of skin through an aperture. After formation of a suction blister, a blade is actuated to sever a suction cup thereby detaching the means for creating suction at the aperture and at the same time removing the roof of the suction blister to expose an area of dermis from which the skin'"'"'s epidermis has been removed. A rotatable portion of the apparatus is then moved into a position in which a port communicates with a compartment within the rotatable portion. The compartment may contain a reservoir of fluid substance to be transdermally absorbed or may contain means for taking a sample of exudate produced at the exposed dermis. A modified apparatus has means for applying suction to the exposed dermis to enhance the rate at which exudate is formed and for handling a sample of exudate for analysis. Transdermal delivery and sampling are thereby achieved non-invasively and without the impediment of the skin'"'"'s epidermis.

Claims

1. A transdermal perfusion apparatus, comprising:

a housing including a base having a skin contact surface that defines an aperture, and further including a moveable portion that defines an access port and at least one opening and which includes at least one compartment;

means for operably securing said skin contact surface in sealing contact with an area of skin to be transdermally perfused;

wherein in a first position of said moveable portion, said access port is alignable in registration with said aperture to facilitate formation of a de-epithelialized skin erosion within said aperture; and

wherein in a second position of said moveable portion, one said opening is alignable in registration with said aperture to provide communication between said aperture and said compartment.

2. The apparatus of claim 1, wherein:

said moveable portion is a rotatable portion rotatable about a rotation axis; and

said access port is defined at an eccentric location of said moveable portion relative to said rotation axis.

3. The apparatus of claim 2, wherein said at least one opening is located eccentrically relative to said rotation axis of said rotatable portion.

4. The apparatus of claim 3 comprising a continuous seal extending peripherally of said access port and operable between said rotatable portion and said base.

5. The apparatus of claim 4, further comprising a second continuous seal extending peripherally of said opening at a location eccentric relative to said rotational axis such that said opening is moveable by rotation of said rotatable portion into registration with said aperture.

6. The apparatus of claim 5, wherein said continuous seal and said second continuous seal are integrally formed.

7. The apparatus of claim 2, further comprising an actuating mechanism operable to facilitate rotational movement of said rotatable portion relative to said base in response to movement of an actuating member of said mechanism.

8. The apparatus of claim 2, wherein said actuating mechanism comprises a geared pinion mounted on said base for rotation by movement of said actuator and a circumferential rack mounted on said rotatable portion and engaged by said pinion.

9. The apparatus of claim 2, wherein:

said rotatable portion defines a sampling port at an eccentric location relative to said rotation axis of said rotatable portion;

the apparatus further comprising a sampling piston reciprocatable in said sampling port to vary volume of a sampling chamber defined therein whereby suction may be created in said sampling chamber, said sampling port being locatable by rotation of said rotatable portion in registration with said aperture defined in said base such that said aperture communicates with said sampling chamber.

10. The apparatus of claim 9, wherein:

said sampling piston defines a bore to receive an outflow of fluid from said sampling chamber;

the apparatus further comprising an openable closure operable to close said bore to maintain suction in said sampling chamber.

11. The apparatus of claim 10, further comprising a sampling device connectable to said sampling piston and defining a sampling channel communicating in use with said bore to receive a sample of fluid from said sampling chamber.

12. The apparatus of claim 10, wherein said sampling piston is reciprocatable in said sampling port by means of co-operable screw threaded formations of said sampling piston and said rotatable portion.

13. The apparatus of claim 2, wherein said rotatable portion includes:

a plurality of openings defined at eccentric locations relative to said rotation axis; and

wherein rotation of said rotatable portion brings successive ones of said openings into alignment registration with said aperture and with at least some of said plurality of compartments.

14. The apparatus of claim 13, wherein:

said moveable portion of said housing includes at least first and second said compartments comprising reservoirs containing respective first and second fluids; and

said first and second fluids may be separately and sequentially communicated to said aperture via respective said openings by successively sequentially rotating said rotatable portion.

15. The apparatus of claim 3, wherein said moveable portion includes at least two compartments and at least one of said compartments contains means for sampling body fluids communicated to the compartment from said aperture via a respective said opening.

16. The apparatus of claim 1, wherein said moveable portion includes a chamber sized to receive a patch;

and further including;

an applicator to deploy said patch from said chamber through said aperture into engagement with an erosion of skin produced by said apparatus.

17. The apparatus of claim 16, wherein said applicator further reciprocally deploys said patch away from a region of said erosion of skin.

18. The apparatus of claim 16, further including said patch.

19. The apparatus of claim 16, wherein said applicator comprises a holding means for holding said patch in a stowed position, and an actuator operable to displace said patch from said stowed position into a deployed position via said opening.

20. The apparatus of claim 19, wherein said holding means comprises at least one pin extending at least partially through said patch.

21. The apparatus of claim 20, wherein said actuator comprises a plunger that is moveable to separate said patch from at least said at least one pin and impel said patch into said deployed position.

22. The apparatus of claim 16, wherein said patch comprises a protective film overlaying an adhesive surface thereof, the apparatus further comprising separating means for operably dissociating said protective film from said patch.

23. The apparatus of claim 22, wherein said separating means comprises a blade and means for moving said blade between said protective film and the said patch.

24. The apparatus of claim 23, further comprising means for moving said blade so as to traverse said access port when aligned with said aperture to effect disruption of a suction blister in use during formation of said de-epithelialized skin erosion.

25. The apparatus of claim 1, further including a suction cup, in communication with said access port, to subject skin beneath said aperture to suction to facilitate formation of a de-epithelialized skin erosion within said aperture.

26. The apparatus of claim 25, wherein said suction cup includes:

a lip portion extending peripherally of said aperture;

an outlet port; and

a suction chamber communicating with said outlet port and with said aperture; and

wherein said apparatus further includes;

suction means for supplying suction to said suction chamber and said outlet port;

cutting means for severing from said lip portion a removable portion of said suction cup defining said outlet port.

27. The apparatus of claim 26, comprising an actuator mounted on said housing;

wherein said cutting means comprises a blade moveable to sever said removable portion in response to movement of said actuator relative to said housing.

28. The apparatus of claim 26, wherein said suction means defines an expansion chamber communicating with said outlet port via a tube, said suction means being operable to expand volume of said expansion chamber from an initial volume to an expanded volume, and further comprising locking means operably maintaining said expansion chamber in said expanded volume.

29. The apparatus of claim 28, wherein said suction means comprises a syringe.

30. The apparatus of claim 26, wherein said suction means comprises a connector releasably engagable with said outlet port, wherein disengagement of said connector from said outlet port admits ambient air to said suction chamber.

31. The apparatus of claim 30, comprising an arming device operable to prevent actuation of said cutting means until said connector has been disconnected from said outlet port.

32. The apparatus of claim 31, wherein said arming device comprises an arming pin insertable into said housing to a location in which it prevents relative movement of the actuator and housing, said arming device further comprising a handle connected to said connector and to said arming pin.

33. The apparatus of claim 26, wherein said suction cup comprises a cylindrical portion intermediate said lip and said outlet port and having a cylindrical axis substantially orthogonal to said contact surface, and wherein said cutting means is operable to sever said cylindrical portion at a predetermined location spaced from said lip portion.

34. The apparatus of claim 25, wherein said suction cup comprises an internal surface that is adhesively coated.

35. The apparatus of claim 25, further including:

a tube, communicating with said suction cup and operatively coupleable to a means for creating suction; and

an indicator, responsive to displacement of air in said tube, to indicate volumetric displacement of air from said suction cup in response to formation of a suction blister.

36. The apparatus of claim 25, further including:

a tube, communicating with said suction cup, operatively coupleable to a means for creating suction; and

an indicator, responsive to displacement of air in said tube, to indicate volumetric displacement of air from said suction cup in response to an ingress of body fluid therein during a period when suction is maintained within said suction cup.

37. The apparatus of claim 35, wherein said indicator comprises a slug of liquid contained within said tube and indicating means for indicating an extent of linear displacement of said slug of liquid through said tube.

38. The apparatus of claim 36, wherein said indicator comprises a slug of liquid contained within said tube and indicating means for indicating an extent of linear displacement of said slug of liquid through said tube.

39. The apparatus of claim 37, wherein said indicator further comprises a clamp securable at an adjustable position along said tube, and wherein said indicating means is supported by said clamp.

40. The apparatus of claim 38, wherein said indicator further comprises a clamp securable at an adjustable position along said tube, and wherein said indicating means is supported by said clamp.

41. The apparatus of claim 39, further including a linear scale supported by said clamp, wherein movement of said slug of liquid from an initial position is measurable by reading indicia of said scale in registration with said slug of liquid.

42. The apparatus of claim 40, further including a linear scale supported by said clamp, wherein movement of said slug of liquid from an initial position is measurable by reading indicia of said scale in registration with said slug of liquid.

43. The apparatus of claim 35, wherein said indicating means comprises an electro-optic sensor.

44. The apparatus of claim 36, wherein said indicating means comprises an electro-optic sensor.

45. The apparatus of claim 43 comprising a clamp for clamping said sensor on said tube at an adjustable position and datum means for alignment of said clamp relative to an initial position of said slug of liquid such that said sensor is activated when a slug of liquid has been displaced therefrom by a predetermined displacement.

46. The apparatus of claim 44, comprising a clamp for clamping said sensor on said tube at an adjustable position, and datum means for aligning said clamp relative to an initial position of said slug of liquid such that said sensor is activated when a slug of liquid has been displaced therefrom by a predetermined displacement.

47. The apparatus of claim 35, comprising a liquid storage structure connected to said tube and defining a liquid storage chamber communicating with a transparent portion of said tube and means for displacing a quantity of liquid from said liquid storage chamber into said tube to thereby constitute a slug of liquid.

48. The apparatus of claim 36, comprising a liquid storage structure connected to said tube and defining a liquid storage chamber communicating with a transparent portion of said tube and means for displacing a quantity of liquid from said liquid storage chamber into said tube to thereby constitute a slug of liquid.

49. The apparatus of claim 47, wherein said liquid storage structure is deformable to vary volume of said liquid storage chamber in response to variation in internal pressure within said chamber, wherein liquid is displaceable into said tube in response to suction applied within said tube.

50. The apparatus of claim 48, wherein said liquid storage structure is deformable to vary volume of said liquid storage chamber in response to variation in internal pressure within said chamber, wherein liquid is displaceable into said tube in response to suction applied within said tube.

51. The apparatus of claim 1, further including:

means for applying heat to a portion of said contact surface peripheral to said aperture.

52. The apparatus of claim 51, wherein said heating means comprises a resistive heating element and a power circuit operable to pass electrical current through said heating element.

53. The apparatus of claim 52, wherein said power circuit comprises temperature regulating means for operably maintaining a heated portion at a substantially constant undetermined value.

54. The apparatus of claim 53, wherein said value of temperature ranges from about 36°

C. to 43°

C.

55. The apparatus of claim 52 wherein said heating element is formed of a material having a coefficient of resistance which achieves self regulation at the required temperature when supplied from a constant voltage power supply.

56. The apparatus of claim 1, further including a pump to transfer liquid between said aperture and a said compartment via said opening.

57. The apparatus of claim 56 wherein said compartment contains a reservoir of liquid and said pump is operable to deliver metered amounts of liquid from said reservoir to said aperture.

58. The apparatus of claim 56, wherein said compartment contains a receptor and a pump is operable to deliver liquid from said aperture to said receptor.

59. The apparatus of claim 58, wherein said receptor is a bio-sensor operable to analyze liquid sampled from said aperture.

60. The apparatus of claim 56, wherein said pump is an electronically controlled micro pump.

61. The apparatus of claim 1, further including:

an implementing device operably implementing a transdermal procedure at a skin lesion via said at least one opening in said removable portion; and

releasable connecting means for releasably connecting said implementing device and said moveable portion.

62. The apparatus of claim 61, wherein said implementing device comprises a reservoir defining a fluid receiving chamber and an outlet communicating with said opening of said movable portion when said implementing device is operatively connected therewith.

63. The apparatus of claim 62, wherein said implementing device comprises suction means, connected to said opening when said implementing device is operatively connected therewith, for operably creating suction to thereby draw fluid from said fluid receiving chamber into said opening.

64. The apparatus of claim 61, wherein said implementing device comprises a cannula defining said outlet, said movable portion comprising a penetrable septum operable to seal said opening when said implementing device is disconnected and being penetrated by said cannula when said implemented device is connected, wherein said cannula and septum constitute said releasable connecting means.

65. The apparatus of claim 64, wherein said releasable connecting means includes a further cannula and septum of said implementing device and movable portion respectively operable to releasably connect said suction means with said opening.

66. The apparatus of claim 61, wherein:

said housing defines a liquid enclosure, communicating with said aperture, sized to receive a liquid therein; and

said implementing device comprises a syringe, connected to said enclosure, and including;

a piston;

a cylinder sized to receive said piston;

screw threaded actuating means for advancing said piston within said cylinder in metered stages by rotation of an actuator relative to said cylinder;

wherein metered doses of liquid are dispensed into said liquid enclosure.

67. The apparatus of claim 66, further comprising a collecting chamber connected to said enclosure to receive excess liquid.

68. The apparatus of claim 67, wherein said collecting chamber comprises a flexible bag connected to said housing.

69. The apparatus of claim 66, wherein said housing further comprises a closable port communicating with said enclosure to facilitate input of flushing solution.

70. The apparatus of claim 69, wherein said implementing device is a means for inducing an alternating magnetic field in a said compartment of said moveable portion.

71. The apparatus of claim 69, wherein said implementing device is a means for heating a said compartment in said moveable portion.

72. A transdermal perfusion system, comprising:

a transdermal perfusion apparatus, including;

a housing including a base having a skin contact surface that defines an aperture and that is operatively and sealingly securable to an area of skin to be transdermally perfused by a liquid within said housing, said housing further including a moveable portion that defines an access port and at least one opening and that includes at least one compartment; and

a liquid, disposed in one said compartment, to be transdermally perfused by said apparatus;

wherein in a first position of said moveable portion, said access port is alignable in registration with said aperture to facilitate formation of a de-epithelialized skin erosion within said aperture; and

wherein in a second position of said moveable portion, one said opening is alignable in registration with said aperture to provide fluid communication between said aperture and said liquid in said compartment.

73. The transdermal perfusion system of claim 72, wherein said liquid includes a pharmaceutically active agent.

74. The transdermal perfusion system of claim 72, wherein said liquid includes a drug.

75. The transdermal perfusion system of claim 72, 73, or 74, wherein said liquid includes insulin.

76. A transdermal perfusion system, comprising:

a transdermal perfusion apparatus, including;

a housing including a base having a skin contact surface that defines an aperture and that is operatively and sealingly securable to an area of skin to be transdermally perfused by a substance within said housing, said housing further including a moveable portion that defines an access port and at least one opening and that includes at least one compartment; and

a substance, disposed in one said compartment, to be transdermally perfused by said apparatus;

wherein in a first position of said moveable portion, said access port is alignable in registration with said aperture to facilitate formation of a deepithelialized skin erosion within said aperture; and

wherein in a second position of said moveable portion, one said opening is alignable in registration with said aperture to provide communication between said aperture and said substance in said compartment.

77. The transdermal perfusion system of claim 76, wherein said substance includes a drug.

78. The transdermal perfusion system of claim 77, wherein said substance is in gel form.

79. The transdermal perfusion system of claim 77, wherein said substance is in hydrogel form.

80. The transdermal perfusion system of claim 77, wherein said substance is in solid form.

81. The transdermal perfusion system of claim 77, wherein said substance is in liquid form.

82. The transdermal perfusion system of claim 77, wherein said substance is in microsphere mass form.

83. The transdermal perfusion system of claim 77, wherein said substance is in cream form.

84. The transdermal perfusion system of claim 77, wherein said substance is in a slow release drug form.

85. The transdermal perfusion system of claim 84, wherein said slow release drug form includes at least one drug selected from a group consisting of (a) a drug reversibly bound in absorbent biodegradable starch particles, (b) a drug including at least one polymer in non-biodegradable polysaccharide spheres, (c) a drug in microcapsule form including at least one lipid that disintegrates slowly in a biological fluid, (d) a drug in microcapsule form including at least first and second polymers of different types that disintegrate slowly in a biological fluid, and (e) a drug in pro-drug form.