Methods for making controlled delivery devices having zero order kinetics

Patent metadata

Field	Value
Publication number	US-9005649-B2
Application number	US-201013383820-A
Country	US
Kind code	B2
Filing date	Jul 14, 2010
Priority date	Jul 14, 2009
Publication date	Apr 14, 2015
Grant date	Apr 14, 2015

Abstract

A method of making an injectable or implantable active agent delivery device capable of delivering a diagnostic, therapeutic, and/or prophylactic agent to a desired targeted site having orifice(s) on the surface is disclosed herein providing unidirectional release of the agent at a controlled desirable rate. The agent may include, but is not limited to, drugs, proteins, peptides, biomarkers, bioanalytes, and/or genetic material. The technology of the invention is based on parallel processing to fabricate micro-holes on tubes employing photo-lithography and reactive ion etching techniques and also incorporates a simple molding method to form the micro-holes on flexible polymer tubes, including bio-degradable tubes. The parallel processing method of the instant invention is fast, economical and well suited for mass production. The developed device, due to its composite structure, has the ability to combine several release mechanisms, leading to zero-order release kinetics for most of the time.

First claim

What is claimed is:

1. A method for making a device for delivery of one or more active agents with zero-order kinetics comprising the steps of:
providing a mold of a non-planer enclosure comprising a first surface and a second surface, wherein the first surface comprises one or more trenches, cavities or depressions, wherein each of the one or more trenches, cavities or depressions comprise one or more holes or perforations;
placing a first substrate in the trenches, cavities or depressions, wherein the substrate may optionally be held in place in the trench by using an adhesive; and
transferring a shape of the holes or the perforations in the one or more trenches, cavities or depressions to the first substrate by one or more microfabrication techniques to make a non-planer enclosure having a series of passageways that connect an outer surface and an inner area for the delivery of the one or more active agents through the series of passageways with a zero order release kinetics.

2. The method of claim 1 , wherein the shape of the one or more holes or perforations is selected from the group consisting of a triangle, a polygon, an undecagon, a trapezium or trapezoid, a quadrilateral, an icosagon, a star polygon, an annulus, a circle, a crescent, an ellipse, an oval, an arbelos, a Reuleaux triangle, a semicircle, a sphere, an Archimedean spiral, an astroid, a deltoid, a super ellipse, and a tomahawk.

3. The method of claim 1 , wherein the one or more microfabrication techniques are selected from the group consisting of physical etching, chemical etching, reactive ion etching, physical vapor deposition, chemical vapor deposition, liftoff, electroplating, electroless plating, ion milling, laser ablation, plasma torch cutting, lithography, and combinations and modifications thereof.

4. The method of claim 1 , further comprising the optional step of pushing the substrate to the bottom of the trench by using a second substrate, wherein the second substrate is selected from the group consisting of silicon, glass, polymer, stainless steel, metals, alloys, ceramics, semiconductors, dielectrics, and combinations and modifications thereof.

5. The method of claim 1 , further comprising the optional step of flipping the mold prior to the step of transferring the shape, wherein the flipping results in the second surface facing the one or more microfabrication or etching sources, wherein the etching sources are selected from the group consisting of ions, etching gases, plasma, laser beams, and combinations or modifications thereof.

6. The method of claim 1 , wherein the first substrate material is selected from the group consisting of a polymer, a rubber, a metal, a semiconductor, a dielectric, a mineral, a ceramic, and a glass.

7. The method of claim 1 , wherein the method further comprising the step of loading an active agent supply in the device by a method selected from the group consisting of capillary action, dipping, injection, and pressure loading using positive or negative pressures.

8. The method of claim 1 , wherein the one or more active agents comprise a solid, a liquid dosage, a semi-solid, a powder or a hydrogel.

9. The method of claim 1 , wherein the device may optionally be attached to a medical device or a microelectronic circuit, wherein the microelectronic circuit comprises at least one of a sensor, a transmitter, a receiver, a transceiver, a switch, a power supply or a light.

10. The method of claim 9 , wherein the medical device is selected from the group consisting of a stent, an urinary catheter, an intravascular catheter, a dialysis shunt, a wound drain tube, a skin suture, a vascular graft, an implantable mesh, an intraocular device, an eye buckle, a heart valve, and combinations and modifications thereof.

11. The method of claim 1 , wherein the one or more holes or perforations are circular.

12. The method of claim 11 , wherein the circular holes or the perforations range from 1 nanometer-1 centimeter, 100 nanometers-100 microns, 1 micron-50 microns, 10-30 microns, 15-25 microns or 20 microns.

13. The method of claim 1 , wherein the first substrate is a polymer tube and the technique is reactive ion etching using a plasma.

14. The method of claim 1 , further comprising the optional step of polymer coating the device thereby preventing a release of the one or more active agents until the coating is removed, which then causes release of the one or more active agents at a substantially constant rate.

15. The method of claim 14 , wherein the polymer coating is poly(methacrylates), and one or more active agents are selected from the group consisting of drugs, proteins, vitamins, minerals, saccharides, lipids, nucleic acid, peptides, manure, plant nutrients, chemicals, perfumes, fragrances, flavoring agents, animal feed, effervescent gas releasing agents, and combinations and modifications thereof.

16. The method of claim 14 , wherein the drugs are selected from the group consisting of an analgesic agent, an antiinflammatory agent, an antihistaminic agent, an antiallergic agent, a central nervous system drug, an antipyretic agent, a respiratory agent, a steroid, a local anesthetic, a sympathomimetic agent, an antihypertensive agent, an antipsychotic agent, a calcium antagonist, a muscle relaxant, a vitamin, a cholinergic agonist, an antidepressant, an antispasmodic agent, a mydriatic agent, an anti-diabetic agent, an anorectic agent, an antiulcerative agent, an anti-tumor agent, or combinations modifications thereof and the proteins are selected from the group consisting of an immunoglobulin or fragments thereof, a hormone, an enzyme, a cytokine, a biomolecule, and combinations and modifications thereof.

17. A method for making a device for delivery of one or more active agents with zero-order kinetics by a reactive ion etching technique comprising the steps of:
providing a silicon-wafer mold comprising a first surface and a second surface, wherein the first surface comprises one or more trenches, cavities or depressions, wherein each of the one or more trenches, cavities or depressions comprise one or more holes, perforations or patterns wherein the silicon-wafer mold forms a non-planer cylindrical enclosure;
placing a first substrate in the trenches, cavities or depressions, wherein the substrate may optionally be held in place in the trench by using an adhesive, wherein the first substrate comprises a polyimide polymer; and
transferring a shape of the holes, the perforations or the patterns in the one or more trenches, cavities or depressions to the first substrate by using a reactive plasma to make a non-planer enclosure having a series of passageways that connect an outer surface and an inner area for the delivery of the one or more active agents through the series of passageways with a zero order release kinetics.

18. The method of claim 17 , further comprising the optional step of pushing the first substrate to the bottom of the trenches, cavities or depressions by using a second substrate, wherein the second substrate is selected from the group consisting of silicon, glass, polymer, stainless steel, metals, alloys, ceramics, semiconductors, dielectrics, and combinations and modifications thereof.

19. The method of claim 17 , further comprising the optional step of flipping the mold prior to the step of transferring the shape, wherein the flipping results in the second surface facing the reactive plasma.

Assignees

• Ho Paul S
• Stavchansky Salomon
• Bowman Phillip
• Luo Zhiquan
• Wu Zhuojie
• Rastogi Ashish
• Univ Texas

Inventors

• Ho Paul S
• Stavchansky Salomon
• Bowman Phillip
• Luo Zhiquan
• Wu Zhuojie
• Rastogi Ashish

Classifications

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P37/08

  Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14) · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P7/02

  Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors · CPC title

• A61P9/12

  Antihypertensives · CPC title