IMPLANTABLE DEVICE FOR CONTROLLED, EXTENDED DELIVERY OF PARATHYROID HORMONE

• US 20090163895A1
• Filed: 01/23/2009
• Published: 06/25/2009
• Est. Priority Date: 09/04/2002
• Status: Active Grant

• Current Assignee: Microchips Biotech, Inc. (Keratin Biosciences, Inc.)
• Original Assignee: MicroCHIPS Inc.
• Inventors: Ausiello, Dennis, Maloney, John M., Uhland, Scott A., Herman, Stephen J., Polito, Benjamin F., Santini, John T. JR., Prescott, James H.
• Granted Patent: US 8,277,440 B2
• Time in Patent Office: Days
• US Class Current: 604/891.100
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 38/29 Parathyroid hormone, i.e. parathormone; Parathyroid hormone-related peptides
• CPC Class Codes: A61K 9/0009 involving or responsive to electricity, magnetism or acoustic waves; Galenical aspects of sonophoresis, iontophoresis, electroporation or electroosmosis microelectromechanical systems A61K9/0097
• 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 9/0036 Devices retained in the vagina or cervix for a prolonged period, e.g. intravaginal rings, medicated tampons, medicated diaphragms
• 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

Abstract

Method and devices are provided for extended and controlled delivery of parathyroid hormone to a patient. The method includes implanting a medical device into the patient, the medical device comprising a substrate, a plurality of reservoirs in the substrate, a release system contained in each of the reservoirs, wherein the release system comprises parathyroid hormone; and controllably releasing a pharmaceutically effective amount of the parathyroid hormone from the reservoirs. The parathyroid hormone can be released intermittently, such as once daily over an extended period (e.g., two months, ten months, or more.). The device can further include reservoirs containing a bone resorption inhibitor or other drug for release. The devices are useful in delivering PTH for the treatment and prevention of bone loss, such as associated with osteoporosis.

Claims

1. An implantable device for the extended, controlled delivery of parathyroid hormone to a patient in need thereof comprising:

a substrate having a plurality of discrete reservoirs therein;

a release system contained in each of the reservoirs, wherein the release system comprises parathyroid hormone in a dried or lyophilized form; and

a control means for selectively releasing a pharmaceutically effective amount of the parathyroid hormone from the reservoirs in daily intermittent doses of between about 10 and 300 μ

g.

2. The device of claim 1, which is adapted to release the parathyroid hormone once daily over a period of at least six months.

3. The device of claim 1, wherein the parathyroid hormone is recombinantly synthesized.

4. The device of claim 1, wherein the parathyroid hormone is a fragment of the complete human hormone that promotes bone growth responsible for bone growth promotion or an analog thereof in which the amino acid sequence is modified yet retains its bone growth promotion property.

5. The device of claim 1, wherein the parathyroid hormone consists essentially of hPTH 1-34, hPTH 1-38, or hPTH 1-28.

6. The device of claim 1, wherein the control means comprises (i) reservoir caps covering the release system of the discrete reservoirs and (ii) a means for actively disintegrating the reservoir caps.

7. The device of claim 6, wherein the means for actively disintegrating comprises a power source for passing an electric current or potential through the reservoir caps.

8. The device of claim 7, wherein the means for actively disintegrating the reservoir caps includes electrical input and output leads electrically connected to each of the reservoirs caps, the input and output leads and the reservoir caps being constructed to provide that the reservoir caps rupture by electrothermal ablation upon said passing of an electric current through the reservoir caps.

9. An implantable device for controlled delivery of parathyroid hormone to a patient in need thereof comprising:

a substrate having a plurality of discrete reservoirs;

a quantity of parathyroid hormone contained in each of the reservoirs;

a plurality of reservoir caps separating said quantity of parathyroid hormone from an environment outside of the reservoirs, and preventing the parathyroid hormone from being released from the implantable device; and

means for disintegrating one or more of the discrete reservoir caps to release the parathyroid hormone from one or more of the reservoirs,

wherein each of said reservoir caps comprise a multi-layer metal structure.

10. The device of claim 9, wherein the multi-layer structure comprises platinum and titanium.

11. The device of claim 9, wherein the parathyroid hormone in a dried or lyophilized form.

12. The device of claim 9, which includes a control means for selectively releasing a pharmaceutically effective amount of the parathyroid hormone from the reservoirs in daily intermittent doses of between about 10 and 300 μ

g.

13. The device of claim 9, which is adapted to release the parathyroid hormone once daily over a period of at least six months.

14. The device of claim 9, wherein the parathyroid hormone is recombinantly synthesized.

15. The device of claim 9, wherein the parathyroid hormone is a fragment of the complete human hormone that promotes bone growth responsible for bone growth promotion or an analog thereof in which the amino acid sequence is modified yet retains its bone growth promotion property.

16. The device of claim 9, wherein the parathyroid hormone consists essentially of hPTH 1-34, hPTH 1-38, or hPTH 1-28.

17. The device of claim 9, wherein the means for actively disintegrating comprises a power source and electrical input and output leads electrically connected to each of the reservoirs caps, the input and output leads and the reservoir caps being constructed to provide that the reservoir caps rupture by electrothermal ablation upon said passing of an electric current through the reservoir caps.