Apparatus and methods for noninvasive blood substance monitoring

• US 5,291,887 A
• Filed: 06/02/1992
• Issued: 03/08/1994
• Est. Priority Date: 06/02/1989
• Status: Expired due to Term

• Current Assignee: Anesta Corporation (Teva Pharmaceutical Industries Limited)
• Original Assignee: Anesta Corporation (Teva Pharmaceutical Industries Limited)
• Inventors: Zhang, Jie, Stanley, Theodore H.
• Primary Examiner(s): Rosenbaum, C. Fred
• Assistant Examiner(s): SMITH, CHALIN A
• Application Number:
  US07/892,287
• Time in Patent Office: 644 Days
• Field of Search: 128/637, 128/760, 128/767, 604/19, 604/20, 604/892.1, 604/891.1, 604/890.1, 604/304, 604/307, 514/975
• US Class Current: 600/573
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement

Abstract

The present invention is directed to novel methods and apparatus for noninvasively collecting substances through mucosal tissues. The concentration of a substance in blood is monitored noninvasively by correlation with the amount of the substance which permeates a mucosal membrane into a substance receiving medium over a specified time period. The substance receiving medium may include an substance permeation enhancer capable of increasing the substance permeability across the mucosal membrane. The substance receiving medium is positioned against the mucosal membrane. After sufficient time delay, the substance receiving medium is removed and analyzed for the concentration of a substance to be measured using known analytical techniques.

The apparatus within the scope of the present invention includes means for supporting the substance receiving medium. The means for supporting the receiving medium provides an added benefit of isolating the substance receiving medium from contamination sources. Such means for supporting the substance receiving medium may include a housing defining a receiving chamber therein which holds the substance receiving medium and an opening to the receiving chamber. The apparatus also preferably includes means for temporarily positioning the substance receiving medium against the mucosal membrane.

The present invention also naturally utilizes the mucosa as filter membrane to exclude compounds in plasma that would interfere with any analysis or make any analysis more difficult. Analysis of substances in receiving medium may be significantly easier than in plasma. An artificial membrane may be used to further exclude other undesirable compounds.

Claims

1. An apparatus for noninvasively collecting a desired substance from a subject comprising:

a) a substance receiving medium the substance receiving medium being capable of receiving the desired substance such that a quantity of the substance, which directly correlates with a subject'"'"'s blood substance value, is capable of permeating the mucosal membrane into the substance receiving medium;

b) means for supporting the substance receiving medium against mucosal tissue of a subject from which the desired substance is to be collected; and

c) means for isolating the substance receiving medium from contaminating sources, such that a quantity of the substance to be collected permeates into the substance receiving medium in a concentration approximately proportional to the concentration of such substance in the subject'"'"'s blood.

2. An apparatus for noninvasively collecting a substance from a subject as recited in claim 1, wherein the apparatus further comprises means for temporarily positioning the substance receiving medium against the mucosal membrane such that substances may be collected from mucosal tissues.

3. An apparatus for noninvasively collecting a substance as defined in claim 2, wherein the temporarily positioning means comprises a handle attached to the housing to facilitate positioning of the apparatus against the mucosal membrane and removal of the apparatus.

4. An apparatus for noninvasively collecting a substance as defined in claim 1, wherein the means for supporting the substance receiving medium comprises a housing defining a receiving chamber therein and an opening to the receiving chamber.

5. An apparatus for noninvasively collecting a substance as defined in claim 1, wherein the means for isolating the substance receiving medium comprises a housing defining a receiving chamber therein and an opening to the receiving chamber.

6. An apparatus for noninvasively collecting a substance as defined in claim 1, further comprising a means for sealing the substance receiving medium from potential contaminants, the sealing means covering the substance receiving medium from the surrounding environment so as to prevent environmental contamination of the substance receiving medium.

7. An apparatus for noninvasively collecting a substance as defined in claim 6, wherein the sealing means comprises a seal constructed around the means for supporting the substance receiving medium against the mucosal membrane.

8. An apparatus for noninvasively collecting a substance as defined in claim 7, wherein the seal comprises polyethylene.

9. An apparatus for noninvasively collecting a substance as defined in claim 3, further comprising means for accessing the receiving chamber such that the substance receiving medium may be introduced into the receiving chamber or removed therefrom while the housing is positioned against the mucosal membrane.

10. An apparatus for noninvasively collecting a substance as defined in claim 1, further comprising a permeation enhancer capable of increasing the substance permeability across the mucosal membrane.

11. An apparatus for noninvasively collecting a substance as defined in claim 1, wherein the substance receiving medium comprises water.

12. An apparatus for noninvasively collecting a desired substance from a subject as in claim 1, further comprising means for joining the substance receiving medium to the mucosal tissue such that communication is established and the desired substance may travel therebetween.

13. An apparatus for noninvasively collecting a substance as defined in claim 12, wherein the means for joining the substance receiving medium to the mucosal membrane comprises a hydrogel.

14. An apparatus for noninvasively collecting a substance as defined in claim 12, wherein the means for joining the substance receiving medium to the mucosal membrane comprises a cream.

15. An apparatus for noninvasively collecting a substance as defined in claim 12, wherein the means for joining the substance receiving medium to the mucosal membrane comprises a suspension.

16. An apparatus for noninvasively collecting a substance as defined in claim 12, wherein the means for joining the substance receiving medium to the mucosal membrane comprises an emulsion.

17. An apparatus for noninvasively collecting a substance as defined in claim 12, wherein the means for joining the substance receiving medium to the mucosal membrane comprises a semisolid composition.

18. An apparatus for noninvasively collecting a substance as defined in claim 1, further comprising means for regulating the substance permeation rate in order to provide a calibrated permeation rate despite variations in substance permeation from individual to individual and from time to time.

19. An apparatus for noninvasively collecting a substance as defined in claim 18, wherein the regulating means further comprises at least one rate-regulating membrane placed between the mucosal membrane and the substance receiving medium to regulate the quantity of the desired substance entering the substance receiving medium.

20. An apparatus for noninvasively collecting a substance as in claim 1, wherein the apparatus further comprises means for filtering the fluids traveling from the mucosal membrane to the substance receiving medium.

21. An apparatus for noninvasively collecting a substance as in claim 20, wherein the filtering means comprises a semipermeable membrane for purifying the substance that travels from the mucosal membrane to the substance receiving medium.

22. An apparatus for noninvasively collecting a substance as recited in claim 1, wherein the apparatus further comprises means for continually measuring the substance receiving medium such that removal of the device from the mucosal membrane and contamination of the substance receiving medium is avoided.

23. An apparatus for noninvasively collecting a substance as recited in claim 22, wherein the continual measurement means comprises an elongate tube communicating with the substance receiving medium.

24. An apparatus for noninvasively collecting a substance as in claim 1, wherein the desired substance is alcohol.

25. An apparatus for noninvasively collecting a substance as in claim 1, wherein the desired substance is an intravenous anesthetic.

26. An apparatus for noninvasively collecting a substance as in claim 1, wherein the desired substance is a narcotic.

27. An apparatus for noninvasively collecting a substance as in claim 1, wherein the desired substance is a blood electrolyte.

28. An apparatus for noninvasively collecting a substance as in claim 1, wherein the desired substance is a bronchodilator drug.

29. An apparatus for noninvasively collecting a substance as in claim 1, wherein the desired substance is a cardiac drug.

30. An apparatus for noninvasively collecting a substance as in claim 1, wherein the desired substance is a psychic acting drug.

31. An apparatus for noninvasively collecting a substance as in claim 1, wherein the desired substance is an endogenous peptide.

58. An apparatus for noninvasively collecting a substance as defined in claim 31, wherein the apparatus further comprises a composition capable of reacting with a substance to produce a hormone.

32. An apparatus for noninvasively collecting a substance from a subject comprising:

a housing, the housing being adapted for placement against a subject'"'"'s mucosal tissue, the housing including a chamber which is in communication with the mucosal tissue when the housing is placed against the tissue while being isolated from contamination from sources other than the mucosal tissue; and

a substance receiving medium contained within the chamber, the medium capable of accepting the desired substance.

33. An apparatus for noninvasively collecting a substance as defined in claim 32, wherein the substance receiving medium comprises water.

34. An apparatus for noninvasively collecting a substance as defined in claim 32, wherein the apparatus further comprises a hydrogel as the substance receiving medium.

35. An apparatus for noninvasively collecting a substance as defined in claim 32, wherein the apparatus further comprises a semisolid composition as the substance receiving medium.

36. An apparatus for noninvasively collecting a substance as defined in claim 32, wherein the apparatus further comprises a composition capable of reacting with a substance to form a substantially insoluble product, in proportion to the concentration substance.

37. An apparatus for noninvasively collecting a substance as defined in claim 32, wherein the substance receiving medium further comprises a permeation enhancer capable of increasing the substance permeability across the mucosal membrane.

38. An apparatus for noninvasively collecting a substance as defined in claim 32, further comprising means for regulating the substance permeation rate in order to provide a calibrated permeation rate despite variations in substance permeation from individual to individual and from time to time.

39. An apparatus for noninvasively collecting a substance as defined in claim 32, further comprising means for accessing the receiving chamber such that substance receiving medium may be introduced into the receiving chamber or removed therefrom while housing is positioned against the mucosal membrane.

40. An apparatus for noninvasively collecting a substance as in claim 32, wherein the apparatus further comprises means for filtering the fluids traveling from the mucosal membrane to the substance receiving medium.

41. An apparatus for noninvasively collecting substance as in claim 40, wherein the filtering means comprises a semipermeable membrane for purifying the substance that travels from the mucosal membrane to the substance receiving medium.

42. An apparatus for noninvasively collecting a substance as in claim 32, wherein the apparatus further comprises means for continually measuring the substance receiving medium such that removal of the device from the mucosal membrane and contamination of the substance receiving medium is avoided.

43. An apparatus for noninvasively collecting a substance as recited in claim 42, wherein the continual measurement means comprises an elongate tube communicating with the substance receiving medium.

44. An apparatus for noninvasively collecting a substance as in claim 32, wherein the monitored substance is alcohol.

45. An apparatus for noninvasively collecting a substance as in claim 32, wherein the monitored substance is an intravenous anesthetic.

46. An apparatus for noninvasively collecting a substance as in claim 32, wherein the monitored substance is a narcotic.

47. An apparatus for noninvasively collecting a substance as in claim 32, wherein the monitored substance is a blood electrolyte.

48. An apparatus for noninvasively collecting a substance as in claim 32, wherein the monitored substance is a bronchodilator drug.

49. An apparatus for noninvasively collecting a substance as in claim 32, wherein the monitored substance is a cardiac drug.

50. An apparatus for noninvasively collecting a substance as in claim 32, wherein the monitored substance is a psychic acting drug.

51. An apparatus for noninvasively collecting a substance as in claim 32, wherein the monitored substance is an endogenous peptide or other hormone.

56. An apparatus for noninvasively collecting a substance as defined in claim 32, wherein the apparatus further comprises a composition capable of reacting with a substance to produce a color change.

57. An apparatus for noninvasively collecting a substance as defined in claim 32, wherein the apparatus further comprises a composition capable of reacting with a substance to produce an electric current.

52. An apparatus for noninvasively collecting a desired substance from a subject comprising:

a housing, the housing being adapted for placement against a subject'"'"'s mucosal tissue, the housing including a chamber wherein the desired substance is collected from the mucosal tissue when the housing is placed against the tissue, the chamber being isolated from contamination from sources other than the mucosal tissue; and

at least one rate regulating membrane placed between the mucosal membrane and the chamber to achieve a rate regulating function with regard to the quantity of the desired substance entering the chamber, the chamber receiving the desired substance such that a quantity of a substance, which directly correlates on a real time basis with a subject'"'"'s blood substance concentration, is capable of permeating the mucosal membrane and the rate regulating membrane into the chamber.

53. An apparatus for noninvasively collecting a substance as defined in claim 52, wherein the apparatus further comprises a substance receiving medium contained within the chamber, the medium capable of accepting the desired substance.

54. An apparatus for noninvasively collecting a substance from a subject as in claim 52, wherein the apparatus further comprises means for temporarily positioning the housing against the mucosal membrane such that substances may be collected from mucosal tissues.

55. An apparatus for noninvasively collecting a substance from a subject as in claim 52, wherein the temporarily positioning means is a handle attached to the housing to facilitate positioning of the apparatus against the mucosal membrane and removal of the apparatus.