초록 ▼

The present invention relates to methods and devices used for the formation of microconduits in a tissue. The term "microconduit" refers to a small opening, channel, or hole into, or through, a tissue, that allows transfer of materials by liquid flow, and by electrophoresis, the microconduit being f

The present invention relates to methods and devices used for the formation of microconduits in a tissue. The term "microconduit" refers to a small opening, channel, or hole into, or through, a tissue, that allows transfer of materials by liquid flow, and by electrophoresis, the microconduit being formed upon impact of a plurality of accelerated microparticles with the surface of the tissue. A method is described for forming at least one microconduit in tissue including the steps of: accelerating a plurality of microparticles to a velocity that causes the microparticles to penetrate a region of tissue surface upon impingement of the microparticles on the tissue surface; and directing the microparticle towards the region of tissue surface, thereby causing the microparticles to penetrate the tissue and form a microconduit in the tissue. According to an embodiment, microparticles are accelerated by being hit with a moving, solid surface. In another embodiment, microparticles are accelerated by a flowing gas or liquid. Also described are methods and devices for using microconduits to deliver therapeutic molecules and ions into tissue, or for extraction of chemical analytes out of tissue. Also described is a method of nail piercing to accommodate jewelry.

대표청구항 ▼

The present invention relates to methods and devices used for the formation of microconduits in a tissue. The term "microconduit" refers to a small opening, channel, or hole into, or through, a tissue, that allows transfer of materials by liquid flow, and by electrophoresis, the microconduit being f

The present invention relates to methods and devices used for the formation of microconduits in a tissue. The term "microconduit" refers to a small opening, channel, or hole into, or through, a tissue, that allows transfer of materials by liquid flow, and by electrophoresis, the microconduit being formed upon impact of a plurality of accelerated microparticles with the surface of the tissue. A method is described for forming at least one microconduit in tissue including the steps of: accelerating a plurality of microparticles to a velocity that causes the microparticles to penetrate a region of tissue surface upon impingement of the microparticles on the tissue surface; and directing the microparticle towards the region of tissue surface, thereby causing the microparticles to penetrate the tissue and form a microconduit in the tissue. According to an embodiment, microparticles are accelerated by being hit with a moving, solid surface. In another embodiment, microparticles are accelerated by a flowing gas or liquid. Also described are methods and devices for using microconduits to deliver therapeutic molecules and ions into tissue, or for extraction of chemical analytes out of tissue. Also described is a method of nail piercing to accommodate jewelry. mono-alkoxy polyethylene glycol mono(meth) acrylates, including mono-methoxy triethylene glycol mono (meth) acrylate, mono-meth oxy tetraethylene glycol mono (meth) acrylate, polyethylene glycol mono (meth) acrylate; other hydrophilic acrylates such as 2-hydroxyethylmethacrylate, glycerylmethacrylate; acrylic acid and its salts; acrylamide and acrylonitrile; acrylamidomethylpropane sulfonic acid and its salts, cellulose, cellulose derivatives such as methyl cellulose ethyl cellulose, carboxymethyl cellulose, cyanoethyl cellulose, cellulose acetate, polysaccharides such as amylose, pectin, amylopectin, alginic acid, and crosslinked heparin. 3. The catheter of claim 1, wherein the first layer is cross-linked to the polymeric elongate member by the application of ultraviolet radiation. 4. The catheter of claim 1, wherein the second layer is cross-linked to the first layer by the application of ultraviolet radiation. 5. The catheter of claim 1, wherein the external coating is hydrophilic. 6. The catheter of claim 1, wherein the flexible elongate shaft varies in stiffness, having a proximal portion of a relatively high stiffness and a distal portion of a relatively low stiffness, with an intermediate portion having a stiffness between that of the proximal portion and that of the distal portion. 7. The catheter of claim 1, wherein the flexible elongate shaft includes a braided support member. 8. The catheter of claim 1, wherein the polymeric elongate member is comprised of a material selected from the group consisting of polyethylene, polypropylene, polyurethane, a block copolymer of polyamide, silicone, Nylon, polyvinyl chloride, polyethylene terepthalate, polyester elastomer tubing, a polymer outer core with a metallic mesh inner core, and laminates thereof. 9. The catheter of claim 1, wherein the polymeric elongate member is doped with a radiopaque metallic material. covalent bond, where R2is hydrogen, alkyl, aralkyl, aryl, hydroxy(C2-10)alkyl, amino(C2-10)alkyl, monoalkylamino(C2-10)alkyl, dialkylamino(C2-10)alkyl or carboxyalkyl; Het is selected from the group consisting of where R3,R4and R5are independently hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, trifluoromethyl, halogen, hydroxyalkyl, cyano, nitro, carboxamido, alkoxycarbonylmethyl, carboxymethyl, --CO2Rx,--CH2ORxor --ORx,where Rx,in each instance, is independently one of hydrogen, alkyl or cycloalkyl wherein said alkyl or cycloalkyl groups may optionally have one or more unsaturations; R6is hydrogen, alkyl, aralkyl, aryl, cyano(C2-10)alkyl, hydroxy(C2-10)alkyl, alkoxy(C2-10)alkyl, mono- and di-alkylamino(C2-10)alkyl, or carboxyalkyl; R7is hydrogen, C1-4alkyl, or C2-4alkenyl; R8is hydrogen, alkyl, alkenyl, aralkyl, aryl, hydroxyalkyl, aminoalkyl, monoalkylamino (C2-10)alkyl, dialkylamino(C2-10)alkyl or carboxyalkyl; R12,R13,R14and R15are independently hydrogen, alkyl, aralkyl, aryl, hydroxyalkyl, aminoalkyl, monoalkylaminoalkyl, dialkylaminoalkyl or carboxyalkyl; or R12and R13are taken together to form --(CH2)y--, where y is 2 to 7, while R14and R15are defined as above; or R14and R15are taken together to form --(CH2)q--, where q is 2 to 7, while R12and R13are defined as above; or R12and R14are taken together to form --(CH2)r--, where r is 0 or 1 to 7, while R13and R15are defined as above; X is oxygen or NR9, where R9is hydrogen, alkyl, cycloalkyl or aryl, wherein said alkyl, cycloalkyl or aryl can be optionally substituted with amino, monoalkylamino, dialkylamino, alkoxy, hydroxy, carboxy, alkoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl, aryl, heteroaryl, acylamino, cyano or trifluoromethyl; Ra,Rband Rcare independently hydrogen, alkyl, hydroxy, alkoxy, aryloxy, aryloxy, alkoxycarbonyloxy, cyano or --CO2Rw,where Rwis alkyl, cycloalkyl, phenyl, benzyl, where Rdand Reare independently hydrogen, C1-6alkyl, C2-6alkenyl or phenyl, Rfis hydrogen, C1-6alkyl, C2-6alkenyl or phenyl, Rgis hydrogen, C1-6alkyl, C2-6alkenyl or phenyl, and Rhis aralkyl or C1-6alkyl; n is from zero to 8; and m is from zero to 6. 2. The device of claim 1, wherein R1is C6-10ar(C1-4) alkyl, C6-10aryl, C4-7cycloalkyl(C1-4)alkyl, heterocycle or heterocyclo(C1-4)alkyl, any of which is optionally substituted; and wherein the heterocycle of said heterocycle or heterocyclo(C1-4)alkyl is a 5- to 7-member mono-cyclic, or 9- to 10-member bi-cyclic heterocyclic ring that is saturated or unsaturated, and contains 1 to 3 heteroatoms selected from N, O and S. 3. The device of claim 2, wherein R1is C6-10ar(C1-4) alkyl, C6-10aryl, C4-7cycloalkyl(C1-4)alkyl, any of which is optionally substituted by 1-5 of hydroxy, nitro, trifluoromethyl, halogen, C1-6alkyl, C2-6alkenyl, C6-10aryl, C1-6alkoxy, C6-10ar(C1-6)alkoxy, C1-6aminoalkyl, C1-6aminoalkoxy, amino, mono(C1-4)alkylamino, di(C 1-4)alkylamino, C2-6alkylcarbonylamino, C2-6alkoxycarbonylamino, C2-6alkoxycarbonyl, carboxy, C1-6hydroxyalkyl, C2-6hydroxyalkoxy, (C1-6)alkoxy(C2-6)alkoxy, mono- and di-C1-4alkylamino (C2-6)alkoxy, C2-10mono(carboxyalkyl)amino, bis(C2-10carboxyalkyl)amino, C6-14ar(C1-6) alkoxycarbonyl, C2-6alkynylcarbonyl, C1-6alkylsulfonyl, C2-6alkenylsulfonyl, C2-6alkynylsulfonyl, C6-10arylsulfonyl, C6-10ar(C1-6) alkylsulfonyl, C1-6alkylsulfinyl, C1-6alkylsulfonamido, C6-10arylsulfonamido, C6-10ar(C1-6)alkylsulfonamido, amidino, guanidino, C1-6alkyliminoamino, formyliminoamino, C2-6carboxyalkoxy, C2-6carboxyalkyl, carboxyalkylamino, cyano, trifluoromethoxy, or perfluoroethoxy. 4. The device of claim 1, wherein Het is selected from the group consisting of: where R3,R4and R5are independently hydrogen, C1-4alkyl, C3-7cycloalkyl, C6-14aryl, C6-10ar(C1-4)alkyl, trifluoromethyl, halogen, hydroxyalkyl, cyano, nitro, carboxamido, carboxy, alkoxycarbonyl, carboxymethyl, alkoxycarbonylmethyl, alkoxy, hydroxy, or cycloalkyloxycarbonyl. 5. The device of claim 4, wherein R3,R4and R5are independently hydrogen, methyl, ethyl, propyl, chloro, bromo, trifluoromethyl, hydroxymethyl, methoxy, ethoxy, carboxamido, nitro, phenyl, cyclopropyl, hydroxy, isopropyl, methoxycarbonyl, ethoxycarbonyl and benzyl. 6. The device of claim 1, wherein R3and R4groups are independently hydrogen, C1-12alkyl, or C2-6alkenyl. 7. The device of claim 6, wherein R3and R4are hydrogen. 8. The device of claim 1, wherein R5is hydrogen, halogen, C1-5alkyl, C3-6alkenyl, C3-5cycloalkyl, trifluoromethyl, or C1-4alkoxy. 9. The device of claim 1, wherein Het is: wherein R3and R4are independently selected to be hydrogen or methyl, and R5is selected from the group consisting of hydrogen, methyl, ethyl, propenyl, allyl, propyl, isopropyl, butyl, R-sec-butyl, S-sec-butyl, isobutyl, 1-pentyl, R-2-pentyl, S-2-pentyl, 3-pentyl, S-1-(2-methyl)-butyl, R-2-(3-methyl)-butyl, 1-(3-methyl)-butyl, R-1-(2-methyl)-butyl, cyclopentyl, 2-pyrrolyl, 3-pyrrolyl, 1-hexyl, S-2-hexyl, R-2-hexyl, R-3-hexyl, and S-3-hexyl. 10. The device of claim 9, wherein R5is hydrogen, methyl, ethyl, propyl or isopropyl. 11. The device of claim 1, wherein Z is --SO2-- or a covalent bond. 12. The device of claim 1, wherein R7is hydrogen. 13. The device of claim 1, wherein X is oxygen. 14. The device of claim 1, wherein X is NR9. 15. The device of claim 1, wherein R9is hydrogen or C1-6alkyl, optionally substituted by one, two or three of amino, monoalkylamino, dialkylamino, alkoxy, hydroxy, alkoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl, carboalkoxy, phenyl, cyano, trifluoromethyl, acetylamino, pyridyl, thiophenyl, furyl, pyrrolyl or imidazolyl. 16. The device of claim 1, wherein R9is hydrogen, methyl, ethyl, propyl, n-butyl, benzyl, phenethyl, 2-hydroxyethyl, 3-hydroxypropyl, 4-hydroxybutyl, carboxymethyl or carboxyethyl. 17. The device of claim 1, wherein R8is hydrogen, C1-6alkyl or C6-10aryl (C1-6)alkyl. 18. The device of claim 1, wherein R12,R13,R14and R15are independently one of hydrogen, C1-6alkyl, C6-10ar(C1-6)alkyl, C6-10aryl, C2-10hydroxyalkyl or C2-7carboxyalkyl. 19. The device of claim 18, where