Surgery – Means and methods for collecting body fluids or waste material
Reexamination Certificate
2000-12-14
2003-05-13
Freay, Charles G. (Department: 3746)
Surgery
Means and methods for collecting body fluids or waste material
C604S319000, C604S329000, C600S562000, C600S578000, C600S584000
Reexamination Certificate
active
06562014
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to transdermal agent sampling. More particularly, this invention relates to the transdermal sampling of agents, such as glucose, body electrolytes and substances of abuse, such as but not limited to alcohol and illicit drugs. The present invention uses skin-piercing microblades to enhance the transdermal flux of the agents during transdermal sampling and negative pressure (i.e., partial vacuum) devices which assist the transdermal efflux of fluid (i.e., interstitial fluid) carrying the agent/analyte to be sampled.
BACKGROUND OF THE INVENTION
Obtaining a droplet of blood for the purpose of sampling a constituent (e.g., glucose) is commonly achieved by piercing the skin using a lancet or other blade-like element. Many such skin piercing devices are spring-driven so that the piercing is accomplished automatically by a pen or similar spring-loaded device. See for example, Suzuki et al. U.S. Pat. No. 5,368,047.
May blood sampling devices also apply suction to the wound following piercing by the lancet. The suction assists in obtaining a blood sample of appropriate size for testing blood components such as glucose. See for example, Suzuki et al. U.S. Pat. No. 5,368,047; Swierczek U.S. Pat. No. 5,054,499; Ishibashi U.S. Pat. No. 5,320,607; Haber et al., U.S. Pat. No. 5,231,993; and Swierczek U.S. Pat. No. 5,201,324.
A partial vacuum applied to the skin has also been used in order to create suction blisters wherein the upper epidermis layer of the skin is separated from the dermis layer of the skin. To separate the epidermis from the dermis, a partial vacuum of about 0.25 atm (200 mm Hg) is applied for a period of about 2 hours. Upon separation of the epidermis from the dermis, the epidermis layer is then pierced or removed thereby exposing the underlying dermis layer for subsequent enhanced transdermal delivery of therapeutic agents such as drugs. See for example, Svedman, U.S. Pat. No. 5,441,490.
A partial vacuum has also been used in order to determine blood gas content by applying the partial vacuum to intact skin. The partial vacuum causes “suction effusion fluid” to appear on the skin surface and vaporization of blood gases therefrom. See for example, Kaneyoshi, U.S. Pat. No. 5,417,206.
In addition to sampling blood, attempts have been made to sample interstitial fluid and to correlate the analyte content in the interstitial fluid with that in the blood. See for example, Joseph, U.S. Pat. No. 5,161,532; Erickson et al., U.S. Pat. No. 5,582,184; Brinda, U.S. Pat. No. 5,682,233; Erickson et al., U.S. Pat. No. 5,746,217 and Erickson et al., U.S. Pat. No. 5,820,570. One of the advantages of sampling interstitial fluid is that the wound created in the skin is not as deep as the wound needed for a blood sampling. Thus, interstitial fluid sampling is generally considered less invasive than blood sampling.
There have been attempts to enhance transdermal flux by mechanically puncturing the skin prior to transdermal drug delivery. See for example U.S. Pat. No. 5,279,544 issued to Gross et al., U.S. Pat. No. 5,250,023 issued to Lee et al., and U.S. Pat. No. 3,964,482 issued to Gerstel et al. These devices utilize tubular or cylindrical structures generally, although Gerstel does disclose the use of other shapes, to pierce the outer layer of the skin. Each of these devices provides manufacturing challenges and/or undesirable irritation of the skin.
A number of devices have been developed for sucking snake or insect venom out of skin pierced by a snake bite or insect bite/sting. These devices consist of a suction syringe having an open end which is placed over the skin site bit by the snake or insect. Depressing a piston/plunger causes a partial vacuum to be applied to the skin which results in at least partial extraction of the injected venom. See for example Emerit U.S. Pat. No. 4,287,819 and Emerit WO 97/14452.
However, there is still a need for even less invasive sampling of interstitial fluid for the purpose of determining analyte concentrations in the blood, for example, blood glucose concentrations. Unfortunately, less invasive techniques tend to draw smaller and smaller fluid samples making accurate analyte concentration analysis problematic.
DESCRIPTION OF THE INVENTION
The present invention provides a reproducible, high volume production, low-cost device suitable for transdermally sampling interstitial fluid for measuring the content or concentration of an agent (i.e., a body analyte such as glucose) containined therein. The device comprises a piercing member having a multiplicity of stratum corneum-piercing microblades arranged on a stratum corneum-contacting portion of the device. After the stratum corneum has been pierced by the microblades, a partial vacuum in the range of about 0.1 to about 0.8 atm, and preferably about 0.3 to about 0.7 atm, is applied to the pierced stratum corneum site. The applied negative pressure causes body fluid (i.e., interstitial fluid) to be withdrawn out of the microslits created by the microblades. The microblades have a length of about 25 to 500 &mgr;m, a width of about 10 to 400 &mgr;m, and thickness of about 10 to 100 &mgr;m. Because of their very short length, the microblades pierce only the outermost layer of the skin (i.e., the stratum corneum layer) but do not pierce sufficiently to contact the blood carrying capillaries or nerve endings. Hence, the piercing of the stratum corneum with the piercing member of the present invention causes no significant sensation (i.e., no pain) or bleeding. The body fluid which is accessed through such a shallow cut in the stratum corneum is interstitial fluid. Since glucose concentration in the interstitial fluid correlates to blood glucose levels, the present invention can be used for monitoring the blood glucose level of a human patient. Thus, the invention has particular utility in the management of diabetes.
In spite of their small size, the microblades of the piercing member can be made with an extremely reproducible size and shape so that the microslits formed by the blades puncturing the skin also have a very reproducible size and depth.
In one preferred embodiment of the invention, the piercing member comprises a sheet having a multiplicity of openings therethrough, a multiplicity of microblades integral therewith and extending downward therefrom. The microblades are pressed against the skin, causing the microblades to cut tiny shallow slits through at least the outer stratum corneum layer. Because of their small length (about 0.025 to 0.5 mm), the microblades penetrate only the outermost layer(s) of the skin to access interstitital fluid, but do not penetrate to the depth of the blood carrying capillary beds. The piercing member has a multiplicity of fluid flow pathways therethrough. A suction device connected to the skin distal side of the piercing member applies a partial vacuum in the range of about 0.1 to about 0.8 atm, and preferably about 0.3 to about 0.7 atm, through the openings in the piercing member, to the pierced stratum corneum. The partial vacuum is applied for a period of about 2 to about 30 seconds, and preferably about 5 to about 15 seconds. The partial vacuum is optionally applied through the fluid flow pathways of the piercing member in cases where the piercing member remains in situ on the skin following skin piercing. The applied suction extracts interstitial fluid out of the microslits. Optionally, the interstitial fluid can be drawn through the openings in the sheet for collection and sampling of an analyte or other substance contained therein.
REFERENCES:
patent: 3814097 (1974-06-01), Ganderton et al.
patent: 3964482 (1976-06-01), Gerstel et al.
patent: 4287819 (1981-09-01), Emerit
patent: 4627445 (1986-12-01), Garcia et al.
patent: 5054499 (1991-10-01), Swierczek
patent: 5070886 (1991-12-01), Mitchen et al.
patent: 5161532 (1992-11-01), Joseph
patent: 5201324 (1993-04-01), Swierczek
patent: 5231993 (1993-08-01), Haber et al.
patent: 5250023 (1993-10-01), Lee et al.
patent: 5279544 (1994-01-01), Gross et al.
patent: 5320
Cormier Michel J. N.
Lin Wei-Qi
Theeuwes Felix
Alza Corporation
Bates Owen J.
Belena John F.
Freay Charles G.
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