Implant device for drug delivery

• US 9,770,412 B2
• Filed: 01/23/2015
• Issued: 09/26/2017
• Est. Priority Date: 01/23/2014
• Status: Active Grant

• Current Assignee: Nano Precision Medical, Inc.
• Original Assignee: Nano Precision Medical, Inc.
• Inventors: Mendelsohn, Adam D., Fischer, Kathleen, Yoshie, Tomoyuki
• Primary Examiner(s): Wax, Robert A
• Assistant Examiner(s): Truong, Quanglong N
• Application Number:
  US15/113,165
• Publication Number:
  US 20170000731A1
• Time in Patent Office: 977 Days
• Field of Search: None
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61K 9/0092 Hollow drug-filled fibres, tubes of the core-shell type, coated fibres, coated rods, microtubules or nanotubes
• CPC Class Codes: A61M 31/002 Devices for releasing a drug at a continuous and controlled rate for a prolonged period of time artificial gland structures or devices A61F2/022; intra-uterine contraceptive devices A61F6/14; tampons for introducing into the vagina A61F13/20, A61L15/00; suppositories or bougies for intra-vaginal or intra-uterine application A61K9/02; physical forms of medicinal preparations for sustained or differential drug release A61K9/20, A61K9/50
• CPC Class Codes: B82Y 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites

Abstract

The present invention provides a method for controlling the internal diameter of nanopores to afford nanopore membranes with a zero-order rate of release of a therapeutic agent.

Claims

1. A method of preparing a coated nanoporous membrane comprising a plurality of nanopores, wherein each nanopore has a first open end and an interior, the method comprising:

forming a reaction mixture under vapor deposition conditions in a reaction chamber wherein the reaction mixture comprises a coating agent and the nanoporous membrane, wherein the vapor deposition conditions are Atomic Layer Deposition conditions comprising a temperature of from about room temperature to less than 100°

C.,

such that a portion of the interior of each nanopore is coated with the coating agent to form a coating layer.

2. The method of claim 1, wherein the Atomic Layer Deposition conditions comprise a temperature of from about 50°

C. to less than 100°

C.

3. The method of claim 1, wherein the coating agent comprises tetrakis(dimethylamido)titanium (TDMAT).

4. The method of claim 3, wherein the coating layer comprises titania.

5. The method of claim 1, wherein the plurality of nanopores comprises titania.

6. The method of claim 5, wherein the titania is substantially amorphous.

7. The method of claim 1, wherein the plurality of nanopores nanotubes such that the nanoporous membrane is a nanotube membrane.

8. The method of claim 7, wherein at least 10% of each nanotube interior is coated.

9. The method of claim 7, wherein at least 50% of each nanotube interior is coated.

10. The method of claim 7, wherein at least 75% of each nanotube interior is coated.

11. The method of claim 7, wherein the plurality of nanotubes before the forming step have an internal diameter of between 10 nm to 100 nm.

12. The method of claim 7, wherein the plurality of nanotubes after the forming step have an internal diameter of between 1 nm to 100 nm.

13. The method of claim 7, wherein the nanotube membrane is in contact with a substrate.

14. The method of claim 13, wherein the substrate comprises titanium.

15. The method of claim 1, further comprising:

purging the reaction chamber of the coating agent; and

repeating the forming step.

16. The method of claim 1, wherein the coated nanotube membrane is a titania nanotube membrane comprising a plurality of titania nanotubes, the method comprising:

forming the reaction mixture under Atomic Layer Deposition conditions in the reaction chamber wherein the reaction mixture comprises the coating agent tetrakis(dimethylamido)titanium (TDMAT), and a titania nanotube membrane on a titanium substrate,

such that at least a portion of the interior of the titania nanotube is coated with the titania coating agent to form the titania coating layer.

17. The method of claim 16, further comprising

forming a second reaction mixture under Atomic Layer Deposition conditions comprising a second coating agent and the nanoporous membrane,

such that a portion of the interior of a second nanopore is coated with the second coating agent.

18. A nanopore comprising a coated interior portion, prepared by the method of claim 1.

19. A nanopore membrane comprising:

a plurality of nanopores, each nanopore having a first open end and an interior, wherein at least one nanopore comprises a coating layer on a portion of the interior, wherein the coated interior is prepared by the method of claim 1.

20. A device comprising:

a capsule suitable for implantation;

a reservoir encapsulated by the capsule, wherein the reservoir is suitable for containing a therapeutic agent; and

a nanopore membrane attached to the capsule such that the nanopore membrane is in contact with the reservoir, wherein the nanopore membrane comprises a plurality of nanopores in fluid contact with the reservoir, wherein the nanopores have an interior with a coating layer on at least a portion of the interior,

such that the plurality of nanopores is a diffusion pathway out of the reservoir for the therapeutic agent.

21. The device of claim 20, wherein the plurality of nanopores is the only diffusion pathway out of the reservoir for the therapeutic agent.

22. A titania composition comprising

a titanium substrate;

an amorphous titania layer on the titanium substrate, wherein the titania layer comprises TiO_xC_y, wherein subscript x is from about 1.5 to about 4.0, and subscript y is from 0 to about 1.0; and

at least one layer of TiO_x chemically bound to the amorphous titania layer, wherein subscript x is from about 1.5 to about 4.0.