Patent US6527716B1 successfully refreshed from Google Patents.
US6527716B1
Expired / Lapsed
US
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Microporation of tissue for delivery of bioactive agents
Assignee: MIDCAP FUNDING III AS SUCCESSOR IN INTEREST TO MIDCAP FINANCIAL LLC LLC
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Filing: 1997-12-30
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Granted: 2003-03-04
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Expires: 2017-12-30
Abstract
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 20 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.
Inventors
- 👤 Jonathan A. Eppstein
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-06 16:25
CPC Classifications
A; A61; A61B; A61B18/00; A61B18/04; A61B1/00; A61B1/313; A61N; A61N1/00; A61N1/18; A61N1/32; A61N1/325; A61B18/18; A61B18/20; A61B18/203; A61B17/00; A61B2017/00017; A61B2017/00022; A61B2017/00026; A61B2017/00137; A61B2017/00154; A61B2017/00172; A61B2017/00743; A61B2017/00747; A61B2017/00765; A61B2018/00315; A61B2018/00452; A61M; A61M37/00; A61M37/0092
Claims Analysis
Total Claims: 27
Claim 1
Independent Claim
157 words
A method of delivering a permeant into an organism comprising steps of: porating a biological membrane of an organism at a selected area to form at least one micropore 1-1000 μm in diameter in said biological membrane, comprising the step of ablating the 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; applying an electromagnetic field to the selected area; and 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.
Claim 2
Independent Claim
157 words
A method of delivering a permeant into an organism comprising steps of: porating a biological membrane of an organism at a selected area to form at least one micropore 1-1000 μm in diameter in said biological membrane, comprising the step of ablating the 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; applying an electromagnetic field to the selected area; and 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.
Claim 3
Dependent Claim
33 words
The method of claim 1 , and further comprising the step of applying one or more enhancers, including one or more of sonic energy and mechanically generated pressure gradients to the selected area.
Claim 4
Dependent Claim
53 words
The method of claim 1 , wherein the step of applying an electromagnetic field comprises applying an iontophoretic field to the selected area, wherein the formulation of the permeant has an electrical charge property such that the iontophoretic field induces movement of the permeant into the organism through the at least one micropore.
Claim 5
Dependent Claim
52 words
The method of claim 1 , wherein the step of applying an electromagnetic field comprises applying a magnetic field to the selected area, wherein the formulation of the permeant has a magnetic property such that the magnetic field induces movement of the permeant into the organism through the at least one micropore.
Claim 6
Independent Claim
158 words
A method of detecting presence of an analyte in an organism comprising steps of: porating a biological membrane at a selected area of the organism to form at least one micropore 1-1000 μm in diameter in said biological membrane, comprising the step of ablating the 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; contacting the selected area with a probe compound under conditions whereby the probe compound is taken up in the organism and interacts with an analyte in the organism; and interrogating non-invasively the selected area to obtain information regarding the levels of the analyte in the organism.
Claim 7
Independent Claim
158 words
A method of detecting presence of an analyte in an organism comprising steps of: porating a biological membrane at a selected area of the organism to form at least one micropore 1-1000 μm in diameter in said biological membrane, comprising the step of ablating the 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; contacting the selected area with a probe compound under conditions whereby the probe compound is taken up in the organism and interacts with an analyte in the organism; and interrogating non-invasively the selected area to obtain information regarding the levels of the analyte in the organism.
Claim 8
Dependent Claim
24 words
The method of claim 5 , wherein the step of contacting comprises contacting the selected area with a microparticle carrier incorporating the probe compound.
Claim 9
Dependent Claim
33 words
The method of claim 6 , wherein the microparticle comprises a porous microsphere and the probe compound is a glucose specific fluorophore compound which alters its fluorescence response in the presence of glucose.
Claim 10
Dependent Claim
57 words
The method of claim 5 , wherein the step of interrogating comprises steps of: irradiating the selected area with electromagnetic radiation; and detecting radiation emanating from the selected area in response to the electromagnetic radiation, whereby at least one characteristic of the radiation detected from the selected area is a measure of the analyte in the organism.
Claim 11
Dependent Claim
28 words
The method of claim 8 ,wherein the step of detecting at least one characteristic comprises detecting one or more of amplitude, wavelength, or fluorescent lifetime of the radiation.
Claim 12
Dependent Claim
19 words
The method of claim 8 , wherein the step of irradiating comprises irradiating the selected area with infrared radiation.
Claim 13
Independent Claim
156 words
A method of delivering a nucleic acid into an organism comprising steps of: porating a biological membrane at a selected area of the organism to form at least one micropore 1-1000 μm in diameter in said biological membrane comprising the step of ablating the 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; applying an electromagnetic field to the selected area; and contacting the selected area with a nucleic acid under conditions whereby the electromagnetic field actively induces the flux of the nucleic acid into the organism through the at least one micropore formed in the biological membrane.
Claim 14
Independent Claim
156 words
A method of delivering a nucleic acid into an organism comprising steps of: porating a biological membrane at a selected area of the organism to form at least one micropore 1-1000 μm in diameter in said biological membrane comprising the step of ablating the 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; applying an electromagnetic field to the selected area; and contacting the selected area with a nucleic acid under conditions whereby the electromagnetic field actively induces the flux of the nucleic acid into the organism through the at least one micropore formed in the biological membrane.
Claim 15
Dependent Claim
12 words
The method of claim 11 , wherein the nucleic acid is DNA.
Claim 16
Dependent Claim
12 words
The method of claim 11 , wherein the nucleic acid is RNA.
Claim 17
Independent Claim
171 words
A method for delivering a permeant into an organism comprising steps of: porating a biological membrane at a selected area of the organism to form at least one micropore 1-1000 μm in diameter in said biological membrane, comprising the step of ablating the 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; applying an electromagnetic field to the selected area; and 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, wherein the permeant is selected from the group consisting of insulin, interferon and heparin.
Claim 18
Independent Claim
171 words
A method for delivering a permeant into an organism comprising steps of: porating a biological membrane at a selected area of the organism to form at least one micropore 1-1000 μm in diameter in said biological membrane, comprising the step of ablating the 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; applying an electromagnetic field to the selected area; and 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, wherein the permeant is selected from the group consisting of insulin, interferon and heparin.
Claim 19
Independent Claim
161 words
A method of delivering a permeant associated with a carrier into an organism comprising steps of: porating a biological membrane at a selected area of the organism to form at least one micropore 1-1000 μm in diameter in said biological membrane comprising the step of ablating the 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; applying an electromagnetic field to the selected area; and contacting the selected area with the carrier under conditions whereby the electromagnetic field actively induces the flux of the permeant associated with the carrier into the organism through the at least one micropore formed in the biological membrane.
Claim 20
Independent Claim
161 words
A method of delivering a permeant associated with a carrier into an organism comprising steps of: porating a biological membrane at a selected area of the organism to form at least one micropore 1-1000 μm in diameter in said biological membrane comprising the step of ablating the 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; applying an electromagnetic field to the selected area; and contacting the selected area with the carrier under conditions whereby the electromagnetic field actively induces the flux of the permeant associated with the carrier into the organism through the at least one micropore formed in the biological membrane.
Claim 21
Dependent Claim
11 words
The method of claim 15 , wherein the carrier comprises liposomes.
Claim 22
Dependent Claim
12 words
The method of claim 15 , wherein the carrier comprises lipid complexes.
Claim 23
Dependent Claim
15 words
The method of claim 15 , wherein the carrier is formulated to have a charge.
Claim 24
Dependent Claim
11 words
The method of claim 15 , wherein the carrier comprises microparticles.
Claim 25
Dependent Claim
13 words
The method of claim 15 , wherein the carrier comprises polyethylene glycol compounds.
Claim 26
Independent Claim
145 words
An apparatus for stimulating an immune response in an organism wherein a permeant is delivered into the organism comprising: a heat source, which, when put in substantial physical contact with a selected area of a biological membrane of the organism, is capable of porating the biological membrane at the selected area to form at least one micropore 1-1000 μm in diameter and at a depth coincident with increased concentration of langerhans cells, by delivering sufficient energy to the selected area such that the temperature of tissue-bound water and other vaporizable substances in the selected area is elevated above the vaporization point of the water and other vaporizable substances, thereby removing the biological membrane in the selected area, and wherein the apparatus enables the permeant, when the permeant is put in contact with the selected area, to be taken up through the micropore into the organism.
Claim 27
Independent Claim
145 words
An apparatus for stimulating an immune response in an organism wherein a permeant is delivered into the organism comprising: a heat source, which, when put in substantial physical contact with a selected area of a biological membrane of the organism, is capable of porating the biological membrane at the selected area to form at least one micropore 1-1000 μm in diameter and at a depth coincident with increased concentration of langerhans cells, by delivering sufficient energy to the selected area such that the temperature of tissue-bound water and other vaporizable substances in the selected area is elevated above the vaporization point of the water and other vaporizable substances, thereby removing the biological membrane in the selected area, and wherein the apparatus enables the permeant, when the permeant is put in contact with the selected area, to be taken up through the micropore into the organism.
References Cited (Backward Citations)
US3964482A
Cited
US4340048A
Cited
US4522622A
Cited
US5224928A
Cited
US5651768A
Cited
GB2153233A
Cited
US4758081A
Cited
US4844098A
Cited
US4775361A
Cited
US4767402A
Cited
US4860743A
Cited
US5041109A
Cited
US5003987A
Cited
US5019034A
Cited
US5749847A
Cited
US5019034B1
Cited
US5547467A
Cited
GB2221393A
Cited
US5328453A
Cited
US5362307A
Cited
US5169389A
Cited
US5250023A
Cited
US5190558A
Cited
US5016615A
Cited
US5231975A
Cited
US5323769A
Cited
US5115805A
Cited
US5459127A
Cited
US5092864A
Cited
WO1992000106A2
Cited
US5137817A
Cited
US5279544A
Cited
EP0497620A2
Cited
US5171215A
Cited
US5215520A
Cited
WO1993007801A1
Cited
US5425728A
Cited
US5925035A
Cited
US5817089A
Cited
US5752949A
Cited
US5713845A
Cited
US5423803A
Cited
US5226907A
Cited
US5223219A
Cited
US5246437A
Cited
WO1993020745A1
Cited
US5273525A
Cited
US5462520A
Cited
US5318514A
Cited
US5582586A
Cited
US5421816A
Cited
WO1994008655A2
Cited
WO1994009713A1
Cited
US5380272A
Cited
US5267985A
Cited
US5427585A
Cited
WO1995010223A2
Cited
US5885211A
Cited
US5458140A
Cited
US6142939A
Cited
US5722397A
Cited
US5445611A
Cited
WO1996000110A1
Cited
US5554153A
Cited
WO1996017648A1
Cited
US5879326A
Cited
US5548140A
Cited
WO1996041657A1
Cited
WO1997004832A1
Cited
WO1997007734A1
Cited
US5947921A
Cited
US5801057A
Cited
US6183434B1
Cited
WO1998000193A1
Cited
US5882317A
Cited
WO1998022719A1
Cited
US6027459A
Cited
WO1998029134A2
Cited
US6056738A
Cited
WO1999029364A1
Cited
WO1999044507A1
Cited
US6022316A
Cited
WO1999044508A1
Cited
WO1999044678A1
Cited
WO1999044638A1
Cited
US6173202B1
Cited
WO1999044637A1
Cited
WO2000003758A1
Cited
US6352506B1
Cited
WO2000027473A1
Cited
US6148232A
Cited
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| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
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| 3.5 Years (Year 4) | 2006-03-03 | 2006-09-02 | 2007-03-04 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2010-03-03 | 2010-09-02 | 2011-03-04 | $3760.00 | Window Closed / Lapsed |
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