Microporation of Tissue for Delivery Of Bioactive Agents
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Abstract
A method of enhancing the permeability of a biological membrane, including the skin or mucosa of an animal or the outer layer of a plant to a permeant is described utilizing microporation of selected depth and optionally one or more of sonic, electromagnetic, mechanical and thermal energy and a chemical enhancer. Microporation is accomplished to form a micropore of selected depth in the biological membrane and the porated site is contacted with the permeant. Additional permeation enhancement measures may be applied to the site to enhance both the flux rate of the permeant into the organism through the micropores as well as into targeted tissues within the organism.
10 Citations
141 Claims
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1-73. -73. (canceled)
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74. A method for enhancing the transmembrane flux of a permeant into a selected site of an organism comprising the steps of porating a biological membrane at said selected site to form at least one micropore 1-1000 μ
- m in diameter in said biological membrane by placing a heat conducting element in substantial physical contact with the selected area to deliver sufficient energy by conduction to said selected area of said biological membrane such that the temperature of tissue-bound water and other vaporizable substances in said selected area is elevated above the vaporization point of said water and other vaporizable substances thereby removing the biological membrane in said selected area, wherein the at least one micropore extends to a depth selected from the group consisting of 1-30 microns, 10-200 microns, 100-5000 microns and 1000-10000 microns and wherein the surface area of the site is greater than the total area of the micropores and contacting the porated selected site with a permeant, whereby the permeant is taken up into the organism through at least one micropore formed in the biological membrane.
- View Dependent Claims (75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 141)
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94. A method of enhancing the transmembrane flux of a permeant into an organism comprising steps of:
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(a) porating a biological membrane at a selected area of the organism to form at least one micropore 1-1000 μ
m in diameter in said biological membrane, by placing a heat conducting element in substantial physical contact with the selected area to deliver sufficient energy by conduction to said selected area of said biological membrane such that the temperature of tissue-bound water and other vaporizable substances in said selected area is elevated above the vaporization point of said water and other vaporizable substances thereby removing the biological membrane in said selected area, wherein the at least one micropore extends to a depth selected from the group consisting of 1-30 microns, 10-200 microns, 100-5000 microns and 1000-10000 microns;(b) applying an electromagnetic field to the selected area; and (c) contacting the selected area with a permeant having a formulation and under conditions whereby the electromagnetic field actively induces the flux of the permeant into the organism through the at least one micropore formed in the biological membrane.
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95. A method for transmembrane transport of a vaccine through a biological membrane in a proximity of a site of an organism, comprising:
porating the biological membrane to form at least one micropore 1-1000 μ
m in diameter in said biological membrane by placing a heat conducting element in substantial physical contact with the selected area to deliver sufficient energy by conduction to said selected area of said biological membrane such that the temperature of tissue-bound water and other vaporizable substances in said selected area is elevated above the vaporization point of said water and other vaporizable substances thereby removing the biological membrane in said selected area, wherein the at least one micropore extends to a depth selected from the group consisting of 1-30 microns, 10-200 microns, 100-5000 microns and 1000-10000 microns and wherein the surface area of the site is greater than the total areas of the micropores; and
contacting the selected area with the vaccine under conditions whereby the vaccine is taken up into the organism through at least one micropore formed in the biological membrane.- View Dependent Claims (96, 97, 98, 99, 100, 101, 102, 103)
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114. A method for enhancing the transmembrane flux of a permeant into a selected site of an organism comprising the steps of:
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(i) porating a biological membrane at said selected site to form at least one micropore 1-1000 μ
m in diameter in said biological membrane, wherein said porating of said biological membrane in said site is accomplished by means selected from the group consisting of (a) ablating the biological membrane by contacting said site of said biological membrane with a heat source such that a micropore is formed in said biological membrane at said site;
(b) puncturing said biological membrane with a micro-lancet calibrated to form a micropore;
(c) ablating the biological membrane by a beam of sonic energy onto said biological membrane;
(d) hydraulically puncturing said biological membrane with a high pressure jet of fluid to form a micropore and (e) puncturing said biological membrane with short pulses of electricity to form a micropore, and wherein the at least one micropore extends to a depth selected from the group consisting of 1-30 microns, 10-200 microns, 100-5000 microns and 1000-10000 microns and wherein the surface area of the site is greater than the total area of the micropores; and(ii) contacting the selected area with the permeant under conditions whereby the permeant is taken up into the organism through at least one micropore formed in the biological membrane. - View Dependent Claims (115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140)
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Specification