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| PATENT EXAMPLES |
EXAMPLE 1 In Vitro Enhancement of Skin Permeability Skin permeability changes caused by ultrasound energy were determined by an in vitro diffusion procedure using double chamber cells. The diffusion cells were composed of two separate compartments (4.5 and 5.5 ml) designed to be clamped together across a 1.3 cm diameter opening in the side of each compartment. Magnetic stirring bars in each chamber were used for mixing. Animals were sacrificed using CO.sub.2, and a piece of the dorsal skin removed. Skin specimens were held between the cells with a pressure clamp, the stratum corneum facing the donor solution. The donor compartment contained 20 microCi D-.sup.3 H-mannitol in a saturated solution of D-mannitol in buffered saline solution containing an 0.1M phosphate at pH 7.3. The receiver solution was buffered saline. The cells were placed in the center of a water-filled ultrasonic bath, RAI Research Corporation Model 250, which generated an ultrasonic frequency of 75 kHz in a thermostated stainless steel tank of 3.5".times.3.5".times.2.5". Permeability experiments were performed within the first two hours of switching in the ultrasound. 200 microliter samples were withdrawn from the receiver solution over time, and replaced with 200 microliters of buffered saline. The radioactivity of the withdrawn samples was measured by liquid scintillation counting. All experiments were conducted at room temperature, 22.degree. C. No ultrasound was applied on the controls. Two hours of ultrasound irradiation at 75 kHz of cells containing .sup.3 H-D-Mannitol solution diffusing through the skin of rats and mice in vitro caused a 50 to 80% increase in drug permeation, as shown in FIG. 2. The same effect was observed when the skin was irradiated for two hours before the drug was introduced into the donor cell. Ultrasound irradiation did not damage mouse skin permeability. However, SEM studies show a higher degree of mechanical surface rupture in the in vitro mouse skin irradiated for 2 hours at 75 kHz and relatively high intensity, as compared to a control skin or to mouse skin irradiated in vivo for 1 min. at 870 kHz, 1.5 W/cm.sup.2. |
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