Surgery – Means for introducing or removing material from body for... – Treating material introduced into or removed from body...
Reexamination Certificate
2000-06-05
2003-05-13
Mendez, Manuel (Department: 3763)
Surgery
Means for introducing or removing material from body for...
Treating material introduced into or removed from body...
C604S140000
Reexamination Certificate
active
06562004
ABSTRACT:
FIELD OF THE INVENTION
This invention relates to transdermal delivery of compositions.
BACKGROUND OF THE INVENTION
Despite its often placid appearance, the environment we live in is one that is unrelentingly hostile to human life. In addition to being contaminated by pathogenic microorganisms, the environment is filled with compositions that, if permitted to interact with the internal structures of the human body, would seriously interfere with the many chemical reactions required to sustain life. An important function of the human skin is to limit the entry of undesirable compositions into the human body.
The effectiveness of the skin at excluding harmful compositions from the interior of the human body allows us to freely apply lotions, cosmetics, topical ointments, and insect repellents on the skin with little concern about the toxicity of those compositions. However, this same effectiveness sharply curtails our ability to deliver medicines intended for systemic distribution through the skin and into the bloodstream.
There exist devices that passively deliver compositions through the skin. Because of their reliance on diffusion, only very small molecules can readily be delivered using such passive devices. In addition, the time required to deliver the composition is limited by the rate of diffusion and by the concentration gradient.
There also exist devices that actively deliver compositions through the skin. Such active transdermal delivery devices typically rely on iontophoresis, in which a voltage drives charged molecules of the composition through the skin, phonophoresis, in which ultrasonic waves exert a mechanical force that drives the composition through the skin, and photophoresis, in which a laser assists in the delivery of a composition through the skin. The requirement of complex devices in the latter two cases and the need to ionize the composition in the former case limits the widespread use of these devices.
SUMMARY OF THE INVENTION
The invention is based on the discovery that an explosion can be used to generate a high pressure impulse transient or stress wave that is effective to temporarily enhance the permeability of the skin. The invention provides transdermal delivery devices and methods for safely and efficiently delivering a composition through the skin. These devices include an explosive material that is detonated to generate impulse transients that permeabilize the skin and to thereby allow the composition to diffuse passively through the permeabilized skin. The invention also provides devices and methods for harnessing the forces generated by these impulse transients to actively drive the composition through the temporarily permeabilized skin.
Each impulse transient is a broad-band compressive wave having a rise time of approximately 1 nanosecond and a peak pressure approximately 600 bar less than that overpressure that would cause skin damage. The impulse transient typically has a duration between 100 nanoseconds and 1100 nanoseconds, e.g., 500-700 nanoseconds. The impulse transient is typically generated by detonating an energetic material in the device or by causing an explosive reaction in the device.
A transdermal delivery device according to the invention includes a housing having a partition that divides the housing into a detonation chamber for containing an energetic, or explosive material and a delivery chamber, for containing a composition to be delivered across a patient's skin. The detonation chamber is mechanically coupled to the delivery chamber so that an impulse transient generated within the detonation chamber propagates into and through the delivery chamber and into the patient's skin. The device further includes an energy coupling element for transforming energy provided by an external source into a detonating stimulus for detonating the energetic material in the detonation chamber.
In one embodiment, the transdermal delivery device includes a second partition across the housing so that the housing also includes an expansion chamber that is in mechanical communication with both the detonation chamber and the delivery chamber. The expansion chamber contains an expansion material that expands in volume in response to an impulse transient. Preferably, the expansion chamber is disposed between the detonation chamber and the delivery chamber.
The energy coupling element can be a piezoelectric film in electrical communication with the energetic material in the detonation chamber. Another convenient energy coupling element for the transdermal delivery device is a DC voltage source in electrical communication with the energetic material in the detonation chamber.
The invention also includes a method of manufacturing a transdermal delivery device by dividing a housing into a delivery chamber and a detonation chamber separate from the delivery chamber. An energetic material is then placed in the detonation chamber and a composition to be delivered transdermally can be placed in the delivery chamber. An energy coupling element, or detonator, is then coupled to the energetic material within the detonation chamber for transforming energy provided by an external energy source into a detonating stimulus.
Preferably, the energy coupling element is a piezoelectric material on the housing, the piezoelectric material being in electrical communication with the energetic material. However, the energy coupling element can also include electrodes in communication with the energetic material. The electrodes can be attached to a voltage source when the device is to be detonated.
The method can also include dividing the housing into an expansion chamber in mechanical communication with both the delivery chamber and the detonation chamber. The expansion chamber is then filled with an expansion material selected to expand in volume in response to an impulse transient generated by the energetic material.
A method for delivering a composition across the skin, in accord with the principles of the invention, includes placing, on the skin, a housing having a detonation chamber mechanically coupled to a delivery chamber containing the composition. With the housing on the skin, an energetic material disposed in a detonation chamber is then detonated. This generates an impulse transient that propagates through the delivery chamber and permeabilizes the skin.
In one embodiment, the method also includes providing an expansion chamber in mechanical communication with the detonation chamber and the delivery chamber. This expansion chamber contains an expansion material selected to expand in volume in response to the impulse transient generated within the detonation chamber.
To detonate the energetic material, one deforms a piezoelectric film in electrical communication with the energetic material. This generates an electrical discharge to detonate the energetic material. Alternatively, the energetic material can be detonated by applying a voltage across first and second electrodes in electrical communication with the energetic material.
Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, suitable methods and materials are described below. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. In case of conflict, the present specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and not intended to be limiting.
A transdermal delivery device according to the invention enables the rapid delivery of a composition through the skin by harnessing the energy from an explosion to permeabilize the skin. The explosion is detonated without the intervention of complex devices such as lasers or ultrasound generators. This greatly simplifies the admini
Doukas Apostolos
Flotte Thomas J.
Lee Shun Kwan
Fish & Richardson P.C.
Mendez Manuel
The Massachusetts General Hospital
Thompson Michael M
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