Surgery – Means for introducing or removing material from body for... – Infrared – visible light – ultraviolet – x-ray or electrical...
Reexamination Certificate
2000-03-24
2002-07-23
Pelham, Joseph (Department: 3742)
Surgery
Means for introducing or removing material from body for...
Infrared, visible light, ultraviolet, x-ray or electrical...
C604S021000, C604S022000
Reexamination Certificate
active
06424863
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates generally to the fields of medical physics and drug delivery. More specifically, the present invention relates to a method of continuous delivery of pharmaceutical compounds using electromagnetic energy.
2. Description of the Related Art
Various methods have been used for facilitating the delivery of compounds across the skin and other membranes. lontophoresis uses an electric current to increase the permeation rate of charged molecules. However, iontophoresis is dependent on charge density of the molecule and has further been known to cause burning in patients. Use of ultrasound has also been tested whereby application of ultrasonic energy to the skin results in a transient alteration of the skin, which leads to an increased permeability to substances. Electromagnetic energy produced by lasers may be used to ablate stratum corneum in order to make the skin more permeable to pharmaceutical substances (U.S. Pat. No. 4,775,361), and impulse transients generated by lasers or by mechanical means may be used to make alterations in epithelial layers that result in improved permeation of compounds (U.S. Pat. No. 5,614,502).
Skin has a very thin layer of dead cells, called the stratum corneum, which acts as an impermeable layer to matter on either side of the layer. The stratum corneum primarily provides the skin's barrier function. If the stratum corneum is removed or somehow altered, materials can more easily diffuse into or out of the skin. Alternatively, compounds referred to as permeation enhancers (e.g. alcohol) or drug carriers (e.g. liposome) can be used, with some success, to penetrate the stratum corneum. In any case, the barrier function of the skin presents a very significant problem to pharmaceutical manufacturers who may be interested in topical administration of drugs, or in cutaneous collection of bodily fluids.
Mucosa, the moist lining of many tubular structures and cavities (e.g. nasal sinuses and mouth), consists in part of an epithelial surface layer. This surface layer consists of sheets of cells in single or multiple layers with strong intercellular bonds, and has a non-keratinized or keratinized epithelium. On the basolateral side of the epithelium is a thin layer of collagen, proteoglycans and glucoproteins called the basal lamina, which serves to bind the epithelial layer to the adjacent cells or matrix. The mucosa acts as a barrier to prevent the significant absorption of topically applied substances, as well as the desorption of biomolecules and substances from within the body. The degree to which mucosa acts as a barrier, and the exact nature of the materials to which the mucosa is impermeable or permeable, depends on the anatomical location. For example, the epithelium of the bladder is 10,000 times less “leaky” to ions than the intestinal epithelium.
The mucosa is substantially different from skin in many ways. For example, mucosa does not have a stratum corneum. Despite this difference, permeation of compounds across mucosa is limited and somewhat selective. The most recent model of the permeability of mucosa is that the adjacent cells in the epithelium are tightly bound by occluding junctions, which inhibit most small molecules from diffusing through the mucosa, while allowing effusion of mucoid proteins. The molecular structure of the epithelium consists of strands of proteins which link together between the cells, as well as focal protein structures such as desmosomes. The permeation characteristics of mucosa are not fully understood, but it is conceivable that the selective permeability of the mucosa may depend on its epithelial layer as well as the basal lamina. While it has been shown that removal or alteration of the stratum corneum of skin can lead to an increase in skin permeability, there is no corresponding layer on the mucosa to modify.
There are methods on transdermal drug delivery enhancements using laser ablation or alteration of stratum corneum. More recent technology involves using shock waves to make stratum corneum and cell walls more permeable. One of the problems with the available methods of drug delivery enhancement is that the tissue is altered transiently to be made permeable. Furthermore, there is little or no control over the degree of tissue alteration, and no control over how much drug is delivered.
The prior art is deficient in the lack of effective means of improving the permeation rates of pharmaceutical compounds across biological membranes, e.g. mucosa and skin. Specifically, the prior art is deficient in the lack of effective means of enhancing drug delivery by utilizing non-ionizing electromagnetic energy. The present invention fulfills this long-standing need and desire in the art.
SUMMARY OF THE INVENTION
The present invention describes methods and apparatus for improving the permeation rates of pharmaceutical compounds across biological membranes. Also provided is a method for increasing the diffusion of substances out of tissue.
The present invention uses electromagnetic energy including radiofrequency energy to create propagating pressure waves. These pressure waves can be used to push the drug molecules into the skin or other membranes, or push biomolecules out of the skin. This method allows for continuous and controllable transmembrane drug delivery. In the presence of propagating pressure waves, molecules in a mobile phase (e.g. the drug) would be pushed in the direction of wave propagation while the static phase (e.g. the tissue) would maintain it's position.
In one embodiment of the present invention, there is provided a method for enhancing continuous delivery of a pharmaceutical compound in a subject, comprising the steps of irradiating the subject with electromagnetic energy continuously; and applying the pharmaceutical compound to the subject. The pharmaceutical compound interacts with the electromagnetic energy. Examples of electromagnetic energy include radiofrequency and microwave. Pharmaceutical compound can be an anesthetic drug, an antineoplastic drug, a photodynamic therapeutical drug or any other drug that can interact with electromagnetic energy and be propelled through subject's barrier.
In another embodiment of the present invention, there is provided a method for increasing diffusion rate of a substance in a medium, comprising the step of applying electromagnetic energy to the medium, wherein the electromagnetic energy generates propagating pressure wave upon the medium. The medium can be a liquid or semi-solid medium.
In still another embodiment of the present invention, there is provided a method for improving permeation rate of a molecule through a barrier, comprising the step of applying electromagnetic energy to the barrier, wherein the electromagnetic energy ablates or alters the structure of the barrier. The barrier can be biological and non-biological. Examples of biological barrier include skin, vaginal wall, uterine wall, intestinal wall, buccal wall, tongue, nasopharyngeal wall, anal wall, bladder wall, vascular vessel, lymphatic vessel and urethral vessel.
In yet another embodiment of the present invention, there is provided a method for creating pores in a barrier thereby improving permeation rate of a molecule through the barrier, comprising the step of applying electromagnetic energy with a probe to the barrier, wherein the probe conducts the electromagnetic energy. Specifically, the probe is made of silicon with a metallic conducting material.
In still yet another embodiment of the present invention, there is provided a method for enhancing continuous delivery of a pharmaceutical compound in a subject, comprising the steps of treating the subject to weaken the barrier function of its membrane first; irradiating the pre-treated subject with electromagnetic energy continuously; and applying the pharmaceutical compound to the subject. The subject can be pre-treated with electromagnetic energy, or using other membrane-weakening method.
Further provided in the present invention is a
Flock Stephen T.
Marchitto Kevin S.
Adler Benjamin Aaron
Patel Vinod D
Pelham Joseph
LandOfFree
Delivery of pharmaceutical compounds and collection of... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Delivery of pharmaceutical compounds and collection of..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Delivery of pharmaceutical compounds and collection of... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2877273