Transdermal perfusion of fluids

• US 6,436,078 B1
• Filed: 03/29/2000
• Issued: 08/20/2002
• Est. Priority Date: 12/06/1994
• Status: Expired due to Fees

• Current Assignee: Pal Svedman
• Original Assignee: Pal Svedman
• Inventors: Svedman, Pal
• Primary Examiner(s): Lewis, Kim M.
• Application Number:
  US09/538,372
• Time in Patent Office: 874 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: A61B 5/14521 using means for promoting sweat production, e.g. heating the skin measuring sweat secretion A61B5/4266
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• 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. Apparatus for use in transdermal perfusion procedures comprising a housing, securing means operable to secure a contact surface of the housing in sealing contact with an area of skin in use, an aperture defined in the contact surface and communicating with an access port defined by the housing, a suction cup located in the access port and having a lip portion extending peripherally of the aperture, the suction cup defining an outlet port and a suction chamber communicating with both the outlet port and the aperture, the apparatus further comprising suction means operable to apply suction to the suction chamber in the outlet port and cutting means operable to sever from the lip portion a removable portion of the suction cup defining the outlet port.

2. Apparatus as claimed in claim 1 comprising an actuator mounted on the housing and wherein the cutting means comprises a blade which is movable to sever the removable portion in response to movement of the actuator relative to the housing.

3. Apparatus as claimed in claim 1 wherein the suction means defines an expansion chamber communicating with the outlet port via a tube, the suction means being operable to expand the volume of the expansion chamber from an initial volume to an expanded volume and further comprising locking means operable to maintain the expansion chamber in its expanded volume.

4. Apparatus as claimed in claim 3 wherein the suction means comprises a syringe.

5. Apparatus as claimed in claim 3 comprising an indicator responsive to displacement of air along the tube and operable to provide an indication of volumetric displacement of air from the suction chamber in response to the formation of a suction blister within the suction chamber.

6. Apparatus as claimed in claim 5 wherein the indicator comprises a slug of liquid contained within the tube and indicating means for indicating the extent of linear displacement of the slug of liquid through the tube.

7. Apparatus as claimed in claim 6 wherein the indicator comprises a clamp securable at an adjustable position along the tube and wherein the indicating means is supported by the clamp.

8. Apparatus as claimed in claim 1 wherein the suction means comprises a connector which is releasably engagable with the outlet port whereby disengagement of the connector from the outlet port admits ambient air to the suction chamber.

9. Apparatus as claimed in claim 8 comprising an arming device operable to prevent actuation of the cutting means until the connector has been disconnected from the outlet port.

10. Apparatus as claimed in claim 9 wherein the arming device comprises an arming pin insertable into the housing to a location in which it prevents relative movement of the actuator and housing, the arming device further comprising a handle connected to both the connector and the arming pin.

11. Apparatus as claimed in claim 1 wherein the housing comprises a base defining the contact surface and a rotatable portion in which the access port is defined at an eccentric location relative to the rotation axis of the rotatable portion.

12. Apparatus as claimed in claim 11 wherein the rotatable portion comprises a reservoir having an outlet located eccentrically relative to the rotational axis such that, after the removable portion has been removed, the outlet is locatable by rotation of the rotatable portion in registration with the aperture defined in the base.

13. Apparatus as claimed in claim 12 comprising a continuous seal extending peripherally of the outlet and operable between the rotatable portion and the base.

14. Apparatus as claimed in claim 13 comprising a second continuous seal peripheral to a surface portion of the rotatable portion at a location which is eccentric relative to the rotational axis such that the surface portion is movable by rotation of the rotatable portion into registration with the aperture.

15. Apparatus as claimed in claim 14 wherein the continuous seal and the second continuous seal are integrally formed.

16. Apparatus as claimed in claim 11 comprising an actuating mechanism operable to facilitate rotational movement of the rotatable portion relative to the base in response to movement of an actuating member of the mechanism.

17. Apparatus as claimed in claim 16 wherein the mechanism comprises a geared pinion mounted on the base for rotation by movement of the actuator and a circumferential rack mounted on the rotatable portion and engaged by the pinion.

18. Apparatus as claimed in claim 11 wherein the rotatable portion defines a sampling port at an eccentric location relative to the rotation axis of the rotatable portion, the apparatus further comprising a sampling piston reciprocatable in the sampling port to vary the volume of a sampling chamber defined therein whereby suction may be created in the sampling chamber, the sampling port being locatable, after the removable portion has been removed, by rotation of the rotatable portion in registration with the aperture defined in the base such that the aperture communicates with the sampling chamber.

19. Apparatus as claimed in claim 18 wherein the sampling piston defines a bore to receive an outflow of fluid from the sampling chamber, the apparatus further comprising an openable closure operable to close the bore to maintain suction in the sampling chamber.

20. Apparatus as claimed in claim 19 comprising a sampling device connectable to the sampling piston and defining a sampling channel communicating in use with the bore to receive a sample of fluid from the sampling chamber.

21. Apparatus as claimed in claim 18 wherein the sampling piston is reciprocatable in the sampling port by means of co-operable screw threaded formations of the sampling piston and the rotatable portion.

22. Apparatus as claimed in claim 1 wherein the suction cup comprises a cylindrical portion intermediate the lip and the outlet port and having a cylindrical axis substantially orthogonal to the contact surface and wherein the cutting means is operable to sever the cylindrical portion at a predetermined location spaced from the lip portion.

23. Apparatus as claimed in claim 1 wherein the suction cup comprises an internal surface which is adhesively coated.

24. Apparatus for use in transdermal perfusion procedures comprising a suction cup for use in applying suction to an area of skin, a tube communicating with the suction cup and connectable in use to a suction means, and an indicator responsive to displacement of air along the tube and operable to provide an indication of volumetric displacement of air from the suction cup in response to the formation of a suction blister or the ingress of body fluid within the suction cup during a period in which suction is maintained within the suction cup.

25. Apparatus as claimed in claim 24 wherein the indicator comprises a slug of liquid located in a transparent portion of the tube and indicating means for indicating the extent of linear displacement of the slug of liquid through the tube.

26. Apparatus as claimed in claim 25 wherein the indicating means comprises a clamp securable at an adjustable position along the tube and a linear scale supported by the clamp whereby movement of the slug of liquid from an initial position is measurable by reading indicia of the scale in registration with the slug of liquid.

27. Apparatus as claimed in claim 25 wherein the indicating means comprises an electro-optic sensor.

28. Apparatus as claimed in claim 27 comprising a clamp for clamping the sensor on the tube at an adjustable position and datum means for alignment of the clamp relative to an initial position of the slug of liquid such that the sensor is activated when the slug of liquid has been displaced therefrom by a predetermined displacement.

29. Apparatus as claimed in claim 25 comprising a liquid storage structure connected to the tube and defining a liquid storage chamber communicating with the transparent portion of the tube and means for displacing a quantity of liquid from the liquid storage chamber into the tube to thereby constitute the slug of liquid.

30. Apparatus as claimed in claim 29 wherein the liquid storage structure is deformable to vary the volume of the liquid storage chamber in response to variation in internal pressure within the chamber whereby liquid is displaceable into the tube in response to suction applied within the tube.

31. Apparatus for use in transdermal perfusion procedures, comprising a housing, securing means operable to secure a contact surface of the housing in sealing contact with an area of skin in use, an aperture defined in the contact surface, the housing comprising a base defining the contact surface and a rotatable portion in which an access port is defined at an eccentric location relative to the rotation axis of the rotatable portion and whereby in an initial position of the rotatable portion the access port is aligned in registration with the aperture to facilitate formation of a de-epithelialised skin erosion within the aperture, the rotatable portion further comprising a plurality of openings defined at eccentric locations relative to the rotation axis of the rotatable portion whereby successive openings may be brought into registration with the aperture by rotation of the rotatable portion and a plurality of compartments within the rotatable portion which are accessible via the respective openings.

32. Apparatus as claimed in claim 31, wherein two or more of the compartments comprise reservoirs containing respective fluids whereby the respective fluids may be separately and sequentially communicated to the aperture via respective openings by successive rotational steps of the rotatable portion.

33. Apparatus as claimed in claim 31 wherein one or more of the compartments contains means for sampling body fluids communicated to the compartment from the aperture via the respective opening.

34. Apparatus as claimed in claim 31 comprising an actuating mechanism operable to facilitate rotational movement of the rotatable portion relative to the base in response to movement of an actuating member of the mechanism.

35. Apparatus as claimed in claim 34 wherein the mechanism comprises a geared pinion mounted on the base for rotation by movement of the actuator and a circumferential rack mounted on the rotatable portion and engaged by the pinion.

36. Apparatus for use in transdermal perfusion procedures, comprising a housing, securing means operable to secure a contact surface of the housing in sealing contact with an area of skin in use, an aperture defined in the contact surface and communicating with an access port defined by the housing, means for applying suction to the aperture via the access port and heating means operable to apply heat to a heated portion of the contact surface peripheral to the aperture.

37. Apparatus as claimed in claim 36, wherein the heating means comprises a resistive heating element and a power circuit operable to pass electrical current through the heating element.

38. Apparatus as claimed in claim 37, wherein the power circuit comprises temperature regulating means operable to maintain the heated portion at a substantially constant predetermined value.

39. Apparatus as claimed in claim 38, wherein the value of temperature is in the range 36°

C. to 43°

C.

40. Apparatus as claimed in claim 37 wherein the 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.

41. Apparatus for use in transdermal perfusion procedures, comprising a housing, securing means operable to secure a contact surface of the housing in sealing contact with an area of skin in use, an aperture defined in the contact surface, the surface comprising a base defining the contact surface and a moveable portion in which an access port is defined, the moveable portion being moveable between an initial position in which the access port is aligned in registration with the aperture to facilitate formation of a de-epithelialised skin erosion within the aperture and a second position in which an opening defined by the moveable portion is located in registration with the aperture, and further comprising a pump operable to transfer liquid between the aperture and the compartment via the opening.

42. Apparatus as claimed in claim 41, wherein the moveable portion is rotatable relative to the base, the access port and the opening being eccentrically located relative to the rotational axis thereof.

43. Apparatus as claimed in claim 41 wherein the compartment contains a reservoir of liquid and the pump is operable to deliver metered amounts of liquid from the reservoir to the aperture.

44. Apparatus as claimed in claim 41 wherein the compartment contains a receptor and a pump is operable to deliver liquid from the aperture to the receptor.

45. Apparatus as claimed in claim 44, wherein the receptor is a bio-sensor operable to analyse liquid sampled from the aperture.

46. Apparatus as claimed in claims 41 wherein the pump is an electronically controlled micro pump.

47. Apparatus for use in transdermal perfusion procedures, comprising a housing, securing means operable to secure a contact surface of the housing in sealing contact with an area of skin in use, an aperture defined in the contact surface whereby a de-epithelialised skin erosion may be formed in use via the aperture, the housing defining an enclosure communicating with the aperture and a syringe connected to the enclosure for the delivery of liquid thereto, wherein the syringe comprises a piston and cylinder and screw-threaded actuating means for advancing the piston in metered stages by rotation of the actuator relative to the cylinder to thereby dispense metered doses of liquid.

48. Apparatus as claimed in claim 47, further comprising a collecting chamber connected to the enclosure to receive excess liquid.

49. Apparatus as claimed in claim 48, wherein the collecting chamber comprises a flexible bag connected to the housing.

50. Apparatus as claimed in claim 47 wherein the housing further comprises a closable port communicating with the enclosure to facilitate the input of flushing solution.

51. Apparatus for use in transdermal perfusion procedures, comprising a housing, securing means operable to secure a contact surface of the housing in sealing contact with an area of skin in use, an aperture defined in the contact surface, the housing comprising a base defining the contact surface and a moveable portion in which an access port is defined and whereby in an initial position of the moveable portion the access port is aligned in registration with the aperture to facilitate formation of a de-epithelialised skin erosion within the aperture, the moveable portion further comprising an opening which may be brought into registration with the aperture in a second position of the moveable portion thereby providing communication between a chamber of the moveable portion and the aperture, the apparatus further comprising a transdermal skin patch accommodated within the chamber and a patch applicator operable in use to deploy the patch from the chamber through the aperture into engagement with the skin erosion.

52. Apparatus as claimed in claim 51, wherein the applicator comprises a holding means for holding the patch in a stowed position and an actuator operable to displace the patch from the stowed position into a deployed position via the opening.

53. Apparatus as claimed in claim 52, wherein the holding means comprises at least one pin extending at least partially through the patch.

54. Apparatus as claimed in claim 53, wherein the actuator comprises a plunger which is moveable to separate the patch from the pins and impel the patch into the deployed position.

55. Apparatus as claimed in claim 51 wherein the patch comprises a protective film overlaying an adhesive surface thereof, the apparatus further comprising separating means operable to dissociate the protective film from the patch.

56. Apparatus as claimed in claim 55, wherein the separating means comprises a blade and means for moving the blade between the protective film and the patch.

57. Apparatus as claimed in claim 56, further comprising means for moving the blade so as to traverse the access port when aligned with the aperture to effect disruption of a suction blister in use during formation of the de-epithelialised skin erosion.

58. Apparatus for use in transdermal perfusion procedures. comprising a housing, securing means operable to secure a contact surface of the housing in sealing contact with an area of skin in use, an aperture defined in the contact surface, the housing comprising a base defining the contact surface and a moveable portion in which an access port is defined and whereby in an initial position of the movable portion to access port is aligned in registration with the aperture to facilitate formation of a de-epithelialised skin lotion within the aperture, the movable portion further comprising an opening which may be brought into registration with the aperture in a second position of the movable portion, the apparatus further comprising an implementing device operable in use to implement a transdermal procedure at the skin lesion via the opening and releasable connecting means operable between the movable portion and the implementing device.

59. Apparatus as claimed in claim 58 wherein the implementing device comprises a reservoir defining a fluid receiving chamber and an outlet communicating with the opening of the movable portion when the implementing device is operatively connected therewith.

60. Apparatus as claimed in claim 59 wherein the implementing device comprises suction means connected to the opening when the implementing device is operatively connected therewith and operable to create suction to thereby draw fluid from the fluid receiving chamber into the opening.

61. Apparatus as claimed in claim 58 wherein the implementing device comprises a cannula defining the outlet, the movable portion comprising a penetrable septum operable to seal the opening when the implementing device is disconnected and being penetrated by the cannula when the implemented device is connected whereby the cannula and septum constitute the releasable connecting means.

62. Apparatus as claimed in claim 61 wherein the releasable connecting means further comprises a further cannula and septum of the implementing device and movable portion respectively operable to releasably connect the suction means with the opening.

63. Apparatus for use in sampling transdermal exudate from a de-epithelialised skin erosion, the apparatus comprising an enclosure defining a sampling chamber, securing means operable to sealingly secure a contact surface of the enclosure to an area of skin peripheral to the erosion in use, an aperture defined in the contact surface and communicating with the sampling chamber, an outlet communicating with the sampling chamber for the outflow of exudate, an openable closure for the outlet, and means for applying suction within the sampling chamber to enhance the rate at which exudate is produced.

64. Apparatus as claimed in claim 63 wherein the means for applying suction comprises a piston reciprocatably mounted in the sampling chamber whereby the volume of the sampling chamber is variable.

65. Apparatus as claimed in claim 64 wherein the chamber is cylindrical and receives the piston as a sliding fit therein.

66. Apparatus as claimed in claim 64 wherein the piston defines a bore constituting the outlet extending through the piston and communicating between the chamber and the outlet.

67. Apparatus as claimed in claim 66 wherein the operable closure comprises a cap releasably attachable to the piston.

68. Apparatus as claimed in claim 66 comprising a sampling device releasably connectable to the piston and defining a sampling channel communicating with the bore to receive in use a sample of exudate from the chamber.

69. Apparatus as claimed in claim 68 wherein the sampling device is a transparent cuvette defining a capillary slot constituting the sampling channel and operable to sample exudate from the out let by capillary action.

70. Apparatus as claimed in claim 63 wherein the means for applying suction comprises a syringe connected to an air evacuation port defined by the enclosure.

71. Apparatus as claimed in claim 65 wherein the the outlet is formed in a tubular sidewall of the enclosure, the outlet being overlaid by a resilient sleeve constituting the openable closure.

72. Apparatus for use in transdermal administration of fluids through the skin of a human or animal body, the apparatus comprising a housing attachable to the body, the housing having a contact surface which in use is held in contact with a portion of skin by an adhesive layer, the housing defining a chamber and the contact surface defining an aperture communicating with the chamber, the apparatus further comprising suction means operable during a preparatory phase of operation of the apparatus to apply suction to the skin at a treatment site which is accessible via the aperture such that an area of the skin'"'"'s epidermis at the treatment site is detached from the skin'"'"'s underlying dermis, means for disrupting the detached area of epidermis such that the dermis is exposed within the chamber, and fluid supply means operable during a perfusion phase of operation of the apparatus to supply fluid to the chamber such that fluid in the chamber may be absorbed by the dermis without intervention of the epidermis.