Implantable devices and methods for the evaluation of active agents

• US 10,390,702 B2
• Filed: 03/22/2016
• Issued: 08/27/2019
• Est. Priority Date: 12/30/2011
• Status: Active Grant

• Current Assignee: Kibur Medical Inc.
• Original Assignee: Kibur Medical Inc.
• Inventors: Tepper, Robert I., Fuller, Jason, Jonas, Oliver, Santini, John
• Primary Examiner(s): Osinski, Bradley J
• Application Number:
  US15/077,300
• Publication Number:
  US 20160198989A1
• Time in Patent Office: 1,253 Days
• CPC Class Codes: A61B 10/0266 means for severing sample
• CPC Class Codes: A61B 2010/045 Needles pointed biopsy devices with vacuum aspiration A61B10/0283
• CPC Class Codes: A61B 2562/12 Manufacturing methods specially adapted for producing sensors for in-vivo measurements
• CPC Class Codes: A61B 5/0017 transmitting optical signals transmission by light H04B10/00
• CPC Class Codes: A61B 5/0084 for introduction into the body, e.g. by catheters A61B5/1459 takes precedence
• CPC Class Codes: A61B 5/4848 Monitoring or testing the effects of treatment, e.g. of medication
• CPC Class Codes: A61B 5/6851 Guide wires
• CPC Class Codes: A61B 5/6861 Capsules, e.g. for swallowing or implanting
• CPC Class Codes: A61K 9/0097 Micromachined devices; Microelectromechanical systems [MEMS]; Devices obtained by lithographic treatment of silicon; Devices comprising chips intradermal microneedle arrays A61K9/0021; MEMS in general B81B7/02
• CPC Class Codes: A61M 5/00 Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests vaccination appliances for veterinary use A61D1/025 ; tube connectors, tube couplings, valves or branch units specially adapted for medical use A61M39/00; containers specially adapted for medical or pharmaceutical purposes A61J1/00; combinations of vial and syringe for mixing or transferring their contents A61J1/20; holders for containers for collecting, storing or administering blood or medical fluids A61J1/16
• CPC Class Codes: B33Y 80/00 Products made by additive manufacturing
• CPC Class Codes: F04C 2270/041 Controlled or regulated
• CPC Class Codes: G01N 33/5008 for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics

Abstract

Devices for the local delivery of microdose amounts of one or more active agents, alone or in combination, in one or more dosages, to selected tissue of a patient are described. The devices generally include multiple microwells arranged on or within a support structure. The microwells contain one or more active agents, alone or in combination, in one or more dosages and/or release pharmacokinetics. In an exemplary embodiment, the device has a cylindrical shape, having symmetrical wells on the outside of the device, each well containing one or more drugs, at one or more concentrations, sized to permit placement using a catheter, cannula, or stylet. Optionally, the device has a guidewire, and fiber optics, sensors and/or interactive features such as remote accessibility (such as WiFi) to provide for in situ retrieval of information and modification of device release properties. In the most preferred embodiment, the fiber optics and/or sensors are individually accessible to discrete wells.

Claims

1. An implantable microdevice comprising

a cylindrical support structure having on its curved surface and along the length of the cylindrical support structure a plurality of microwells formed on or within the support structure, the plurality of microwells containing up to a microdose of one or more active agents,

the implantable microdevice having a diameter of between about 0.5 mm and about 2.0 mm, and a length of less than about 5.0 mm, which permit implantation into a tissue using a catheter, cannula, or biopsy needle and removal of the microdevice with the adjacent tissue in spatial orientation with the implantable microdevice using a catheter, cannula, or a biopsy needle with a larger diameter than that of the microdevice,

optionally comprising a guidewire attached to a proximal end of the microdevice.

2. The microdevice of claim 1 wherein the one or more active agents comprises a plurality of active agents, combinations of active agents or active agents with plurality of concentrations or release pharmacokinetics thereof.

3. The microdevice of claim 1 formed by a method selected from the group consisting of lithographic galvanoforming abforming (LIGA), high-aspect-ratio photolithography using a photoresist, microelectro-discharge machining, high-aspect-ratio machining by deep reactive ion etching (DIRE), hot embossing, 3-dimensional printing, stereolithography, laser machining, ion beam machining, and mechanical micro-cutting.

4. The microdevice of claim 1 comprising a guidewire attached to an end of the device, one or more sensors integrated within the implantable microdevice or microwells, and fiber optic or other addressible or interactive means for remote interrogation of the implantable microdevice.

5. The microdevice of claim 1 comprising means for maintaining tissue in a spatial orientation to the microdevice at the time of or after removal of the implantable microdevice.

6. A kit comprising the microdevice of claim 1 and means for insertion or means for removal.

7. The kit of claim 6, wherein the one or more active agents comprises a plurality of active agents, combinations of active agents or active agents with plurality of concentrations or release pharmacokinetics thereof.

8. The kit of claim 6, wherein the microdevice comprises a guidewire attached to an end of the microdevice, one or more sensors integrated within the implantable microdevice or microwells, and fiber optic or other addressible or interactive means for remote interrogation of the microdevice.

9. The kit of claim 6, wherein the microdevice comprises means for maintaining tissue in a spatial orientation to the microdevice at the time of or after removal of the microdevice.

10. The kit of claim 6 wherein the means for insertion is a biopsy cutting needle between 19 and 24 gauge.

11. The kit of claim 6 wherein the means for removal is a biopsy coring needle between 14 and 18 gauge.

12. The kit of claim 6 comprising a sensor for evaluating tissue samples.

13. The implantable microdevice of claim 1, comprising one or more sensors integrated within the implantable microdevice or microwells, and fiber optic or other addressible or interactive means for remote interrogation of the microdevice.

14. A method for assaying tissue for an effective active agent, effective dosage, effective pharmacokinetics of an active agent, or a combination thereof, comprising implanting in a tissue an implantable microdevice and assaying for at least one analyte or removing tissue for analysis,

the implantable microdevice comprising

a cylindrical support structure having on its curved surface and along the length of the cylindrical support structure a plurality of microwells formed on or within the support structure,

the microwells containing up to a microdose of one or more active agents,

the implantable microdevice having a diameter of between about 0.5 mm and about 2.0 mm, and a length of less than about 5.0 mm, which permits implantation into a tissue using a catheter, cannula, or biopsy needle and removal of the microdevice with the adjacent tissue in spatial orientation with the implantable microdevice using a catheter, cannula, or a biopsy needle with a larger diameter than that of the microdevice,

optionally comprising a guidewire attached to a proximal end of the microdevice.

15. The method of claim 14 comprising removing the microdevice and adjacent tissue and analyzing the tissue.

16. The method of claim 14 wherein the tissue is a tumor.

17. The method of claim 14 wherein the tissue is infected or in need of immunomodulation or hormonal treatment.