Long term drug delivery devices with polyurethane based polymers and their manufacture

• US 20050037078A1
• Filed: 08/10/2004
• Published: 02/17/2005
• Est. Priority Date: 08/11/2003
• Status: Active Grant

• Current Assignee: Braeburn Pharmaceuticals, Inc.
• Original Assignee: Valera Pharmaceuticals, Inc. (Endo International PLC)
• Inventors: Kuzma, Petr, Kuo, Sheng-hung
• Granted Patent: US 7,842,303 B2
• Time in Patent Office: Days
• US Class Current: 424/469
• 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: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: A61M 5/14 Infusion devices, e.g. infusing by gravity; Blood infusion; Accessories therefor
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 21/02 Muscle relaxants, e.g. for tetanus or cramps
• CPC Class Codes: A61P 23/00 Anaesthetics
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/08 Antiepileptics; Anticonvulsants
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 33/00 Antiparasitic agents
• CPC Class Codes: A61P 33/06 Antimalarials
• CPC Class Codes: A61P 5/06 of the anterior pituitary hormones, e.g. TSH, ACTH, FSH, LH, PRL, GH
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: B65B 3/003 Filling medical containers such as ampoules, vials, syringes or the like
• CPC Class Codes: Y10T 29/49826 Assembling or joining

Abstract

This invention is related to the use of polyurethane based polymer as a drug delivery device to deliver biologically active compounds at a constant rate for an extended period of time and methods of manufactures thereof. The device is very biocompatible and biostable, and is useful as an implant in patients (humans and animals) for the delivery of appropriate bioactive substances to tissues or organs. The drug delivery device for releasing one or more drugs at controlled rates for an extended period of time to produce local or systemic pharmacological effects comprises: 1. a reservoir, said reservoir comprising; 2. at least one active ingredient; and, optionally, 3. at least one pharmaceutically acceptable carrier; a polyurethane based polymer completely surrounding the reservoir.

Claims

1. A drug delivery device for releasing one or more drugs at controlled rates for an extended period of time to produce local or systemic pharmacological effects, said drug delivery device having a reservoir comprising:

i. at least one active ingredient optionally,

ii. a polyurethane based polymer completely surrounding the reservoir; and

optionally,

iii. at least one pharmaceutically acceptable carrier.

2. The drug delivery device of claim 1 wherein the reservoir is cylindrically shaped.

3. The drug delivery device of claim 2, wherein the polyurethane based polymer is selected from the group comprising:

thermoplastic polyurethane, and thermoset polyurethane.

4. The drug delivery device of claims 2 or 3, where the thermoplastic polyurethane is made of macrodials, diisocyanates, difunctional chain extenders or mixtures thereof.

5. The drug delivery device of claims 2 or 3, where the thermoset polyurethane is made of multifunctional polyols, isocyanates, chain extenders or mixtures thereof.

6. The drug delivery device of claim 5, where the thermoset polyurethane comprises a polymer chain and cross-linking members, said thermoset polyurethane contains unsaturated bonds in the polymer chains and appropriate crosslinkers and/or initiators as cross-linking members.

7. The drug delivery device of claims 2 or 3, where the polyurethane comprises functional groups selected from hydrophilic pendant groups and hydrophobic pendant groups.

8. The drug delivery device of claim 7, wherein the hydrophilic pendant groups are selected from ionic, carboxyl, ether, hydroxyl groups and mixtures thereof.

9. The drug delivery device of claims 2 or 3, wherein hydrophobic pendant groups are selected from alkyl, siloxane groups and mixtures thereof.

17. The drug delivery device of claims 2 or 3, wherein the appropriate conditioning and priming parameters selected from the group consisting of time, temperature, conditioning medium, and priming medium can be selected to establish the desired delivery rates of the active ingredient.

10. A process of manufacturing drug delivery devices made with thermoplastic polyurethanes, said process comprising:

a) precision extrusion or injection molding step to produce a hollow tube made of thermoplastic polyurethane with two open ends with desired physical dimensions;

b) sealing one of the open ends of the hollow tube;

c) loading a reservoir containing a desired formulation containing an active ingredient and optionally, carriers or filling a reservoir with pre-fabricated pellets;

d) sealing the second open end of the hollow tube;

e) conditioning and priming of the drug delivery devices to achieve the desired delivery rates for the actives.

11. The process of manufacturing drug delivery devices made with thermoplastic polyurethanes of claim 10, including the step of inserting pre-fabricated plugs on the open ends of the hollow tube with heat or solvent or by applying heat or solvent while sealing.

12. A process of manufacturing drug delivery devices made with thermoset polyurethanes, said process comprising:

a) precision reaction injection molding or spin casting a hollow tube having two open ends;

b) curing the hollow tube;

c) sealing one end of the hollow tube;

d) loading a reservoir containing a desired formulation containing actives and, optionally, carriers or filling a reservoir with pre-fabricated pellets;

e) sealing the second end of the hollow tube; and

f) conditioning and priming of the drug delivery devices to achieve the desired delivery rates for the actives.

14. The process of manufacturing drug delivery devices made with thermoset polyurethanes of claim 12 or 13, wherein the production of hollow tube and sealing of an open end, is done with an appropriate light-initiated and/or heat-initiated thermoset polyurethane formulation and initiating and curing the light-initiated and/or heat-initiated thermoset polyurethane formulation with light and/or heat or any other means to seal the ends.

15. The process of manufacturing drug delivery devices made with thermoset polyurethanes of claim 12 or 13, wherein the sealing of an open end, is done by inserting a pre-fabricated end plug at the open end of the hollow tube.

16. The process of manufacturing drug delivery devices made with thermoset polyurethanes of claim 12 or 13, wherein the sealing of an open end, is done by inserting a pre-fabricated end plug at the open end of the hollow tube and by applying an appropriate light-initiated and/or heat-initiated thermoset polyurethane formulation on interface between the pre-fabricated end plug and the open end and curing with light and/or heat.

13. A process of manufacturing drug delivery devices made with thermoset polyurethanes, said process comprising:

a) precision reaction injection molding or spin casting a hollow tube having one open end;

b) curing the hollow tube;

c) loading a reservoir containing a desired formulation containing actives and, optionally, carriers or filling a reservoir with pre-fabricated pellets;

d) sealing the open end of the hollow tube; and

e) conditioning and priming of the drug delivery devices to achieve the desired delivery rates for the actives.