Implantable device for long-term delivery of drugs

• US 10,391,288 B2
• Filed: 12/22/2016
• Issued: 08/27/2019
• Est. Priority Date: 03/12/2009
• Status: Active Grant

• Current Assignee: Delpor, Inc.
• Original Assignee: Delpor, Inc.
• Inventors: Martin, Francis J., Kang, Ling-Ling
• Primary Examiner(s): Desanto, Matthew F
• Application Number:
  US15/388,298
• Publication Number:
  US 20170100571A1
• Time in Patent Office: 978 Days
• CPC Class Codes: A61K 31/407 condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
• CPC Class Codes: A61K 31/505 Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61K 47/34 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers A61K47/10 takes precedence
• 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: A61M 37/00 Other apparatus for introducing media into the body for reproduction or fertilisation A61B17/425; apparatus for iontophoresis or cataphoresis A61N1/30; Percutany, i.e. introducing medicines into the body by diffusion through the skin salt baths A61H33/04
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system

Abstract

A device for sustained delivery of a poorly water soluble drug is described. A drug reservoir within the device, when in operation, contains an aqueous suspension of the drug mixed with a suspension of an excipient that, in one embodiment, generates acidic groups for a sustained period of time to maintain a desired pH in the aqueous suspension that in turn provides a constant concentration of a soluble form of the drug.

Claims

1. A method for delivering a sparingly water soluble drug into an environment of use, comprising:

providing a device comprising a porous partition with pores having a pore size and with a porosity, a reservoir and a formulation contained in the reservoir, the formulation comprising a sparingly water soluble drug having a soluble form and an insoluble form and a solubility-modifying excipient that generates acidic groups for a period of between about 2-12 months to provide, when the formulation is hydrated, a concentration of drug in the soluble form that is released across the porous partition and a concentration of drug in the insoluble form that is retained by the porous partition, and

delivering a therapeutic dose of the drug for the period, wherein delivering the therapeutic dose is dependent on pH of the drug formulation and independent of pore size of the porous partition with said porosity.

2. The method according to claim 1, wherein the excipient is a biocompatible, bioerodible polymer.

3. The method according to claim 2, wherein the polymer is selected from the group of polylactides, polyglycolides, copolymers thereof, and polyethyleneglycol.

4. The method according to claim 2, wherein the polymer is a co-polymer of polylactic acid and polyglycolic acid monomeric units, wherein the polylactic acid content is between about 50% to 100%.

5. The method according to claim 1, wherein the solubility-modifying excipient is an erodible polymer or a degradable polymer.

6. The method according to claim 5, wherein the polymer is polymerized from a monomer selected from the group consisting of lactic acid, glycolic acid, lactide, glycolide, ethylene oxide and ethylene glycol.

7. The method according to claim 5, wherein the polymer is a poly(lactic-co-glycolic acid) copolymer.

8. The method according to claim 1, wherein the solubility-modifying excipient is water insoluble.

9. The method according to claim 8, wherein the solubility-modifying excipient is retained by the porous partition.

10. The method according to claim 1, wherein the solubility-modifying excipient is a water insoluble polymer.

11. The method according to claim 10, wherein the solubility-modifying excipient undergoes hydrolysis to form a water-soluble monomer.

12. The method according to claim 1, wherein said drug is a neuroleptic agent.

13. The method according to claim 12, wherein the neuroleptic agent is risperidone, 9-hydroxyrisperidone, olanzapine, or a pharmaceutically acceptable salt thereof.

14. The method according to claim 1, wherein said drug is risperidone.

15. The method according to claim 1, wherein the drug is selected from the group consisting of buprenorphine, paliperidone, asenapine, haloperidol, aripiprazole, and pharmaceutically acceptable salts thereof.

16. A method for treating a patient with a sparingly water soluble drug, comprising:

implanting a device comprising a porous partition with pores having a pore size and with a porosity, a reservoir and a formulation contained in the reservoir, the formulation comprising a sparingly water soluble drug having a soluble form and an insoluble form and a solubility-modifying excipient that generates acidic groups for a period of between about 2-12 months to provide, when the formulation is hydrated to form an aqueous suspension, a concentration of drug in the soluble form that is released across the porous partition and a concentration of drug in the insoluble form that is retained by the porous partition, and

delivering a therapeutic dose of the drug for the period, wherein delivering the therapeutic dose is dependent on pH of the drug formulation and independent of pore size of the porous partition with said porosity.

17. The method according to claim 16, wherein the device is implanted subcutaneously.