Ultrasonic transdermal system for withdrawing fluid from an organism and ...

United States Patent [m

Lipkovker

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US005617851A [ii] Patent Number: 5,617,851 [45] Date of Patent: Apr. 8, 1997

[54] ULTRASONIC TRANSDERMAL SYSTEM FOR WITHDRAWING FLUID FROM AN ORGANISM AND DETERMINING THE CONCENTRATION OF A SUBSTANCE IN THE FLUID

[75] Inventor: Lev M. Lipkovker, Bellevue, Wash.

[73] Assignee: Endodermic Medical Technologies Company, Bellevue, Wash.

[21] Appl. No.: 403,306

[22] Filed: Mar. 14,1995

Related U.S. Application Data

[62] Division of Ser. No. 961,113, Oct. 14, 1992, Pat. No. 5,421,816.

[51] Int. CI.6 A61B 5/00

[52] U.S. CI 128/632; 128/635; 128/760;

128/766

[58] Field of Search 600/19, 22, 317;

128/630, 632, 635, 637, 760, 898, 761-766;

601/2

[56] References Cited

U.S. PATENT DOCUMENTS

4,029,084 6/1977 Soldner.

4,309,989 1/1982 Fahim .

4,372,296 2/1983 Fahim.

4,542,751 9/1985 Webster et al 128/760

4,657,022 4/1987 Holscher 128/635

4,657,543 4/1987 Langer et al 604/891

4,706,676 11/1987 Peck 128/632

4,756,314 7/1988 Eckenhoff et al 128/760

4,767,402 8/1988 Kost et al 604/290

4,780,212 10/1988 Kost et al 210/646

4,787,888 11/1988 Fox 604/20

(List continued on next page.)

A noninvasive method and apparatus for withdrawing fluid from an organism and determining the concentration of a substance in the fluid is disclosed. The noninvasive apparatus comprises a substance concentration sensor (120) that includes an extraction transducer (126) and a substance sensing transducer (133). The extraction transducer includes a container (123); a planar piezoelectric (ultrasonic) transducer (124); a focusing lens (125); and a backing layer (127). The container includes a flange (129) that is attached to the skin of an organism by an adhesive film seal (131). The focusing lens (125) is a plano-concave shape such that the concave side faces the skin of the organism. Thus, the focusing lens (125) defines a cavity (135). Located in the cavity (135) is the substance sensing transducer (133). Positioned above the focusing lens is the ultrasonic transducer (124). A pulse generator (121) is connected to and drives the ultrasonic transducer. A test data processor (122) is connected to the substance sensing transducer (133). Ultrasonic transducer pulses are focused by the focusing lens (125) into the organism, traumatizing the skin underlying the cavity (135). The trauma causes the dermalepidermal junction membrane and the capillary endothelial joints to open and allow fluid to be drawn from the cavity (135). The substance to be detected in the fluid is sensed by the substance sensing transducer (133) causing the output of the transducer to change. The output changes are analyzed by the test data processor (122).

20 Claims, 21 Drawing Sheets

U.S. PATENT DOCUMENTS

4,821,733 4/1989 Peck 128/636

4,821,740 4/1989 Tachibana et al 604/290

4,948,587 8/1990 Kostetal 424/435

4,953,552 9/1990 Demarzo 128/635

4,953,565 9/1990 Tachibana et al 604/290

5,007,438 4/1991 Tachibana et al 128/798 .

5,016,615 5/1991 Driller et al. .

5,019,034 5/1991 Weaver et al 604/20

5,036,861 8/1991 Sembrowich et al 128/763

5,053,001 10/1991 Reller 604/20

5,076,273 12/1991 Schoendorfer et al 128/632

5,080,646 1/1992 Theeuwes et al 604/20

5,084,008 1/1992 Phipps 604/20

5,115,805 5/1992 Bommannan et al. .

5,131,403 7/1992 Haynes 128/760

5,135,478 8/1992 Sibalis 604/20

5,139,023 8/1992 Stanley et al 128/637

5,171,215 12/1992 Flanagan 604/22

5,231,975 8/1993 Bommannan et al 604/20

5,236,414 8/1993 Takasu 604/22

5,267,985 12/1993 Shimadaetal 604/290

5,291,887 3/1994 Stanley et al 128/637

5,323,769 6/1994 Bommannan et al 601/2

OTHER PUBLICATIONS

D. Bommannan et al., "Sonophoresis. I. The Use of High-Frequency Ultrasound to Enhance Transdermal Drug Delivery," Pharmaceutical Research, vol. 9, No. 4, 1992, pp. 559-564.

D. Bommannan et al., "Sonophoresis. II. Examination of the Mechanism(s) of Ultrasound-Enhanced Transdermal Drug Delivery," Pharmaceutical Research, vol. 9, No. 8, 1992, pp. 1043-1047.

J.C. McElnay et al., "The Influence of ultrasound on the percutaneous absorption of fluocinolone acetonide," International Journal of Pharmaceutics, 40(1987), pp. 105-110. Motoaki Shichiri et al., "Wearable Artificial Endocrine Pancreas with Needle-type Glucose Sensor," The Lancet, Nov. 20, 1982, pp. 1129-1131.

Deborah Erickson, "Skinside Out," Scientific American, Nov. 1991, pp. 129-130.

Joseph Kost, "Ultrasound induced delivery of peptides," Journal of Controlled Release, 24 (1993), pp. 247-255.