Hydrophilic polyurethane compositions

• US 10,105,445 B2
• Filed: 02/06/2015
• Issued: 10/23/2018
• Est. Priority Date: 07/05/2006
• Status: Active Grant

• Current Assignee: Ferring BV (Ferring Holding SA)
• Original Assignee: Ferring BV (Ferring Holding SA)
• Inventors: Tuominen, Jukka, Zurutuza, Amaia, Livingstone, Mark Alexander, Halliday, Janet Anne
• Primary Examiner(s): Fisher, Melissa L
• Application Number:
  US14/616,314
• Publication Number:
  US 20150165044A1
• Time in Patent Office: 1,355 Days
• Field of Search: None
• CPC Class Codes: A61K 31/4196 1,2,4-Triazoles
• 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 9/0036 Devices retained in the vagina or cervix for a prolonged period, e.g. intravaginal rings, medicated tampons, medicated diaphragms
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C08G 18/2063 having two nitrogen atoms in the condensed ring system
• CPC Class Codes: C08G 18/4841 containing oxyethylene end groups
• CPC Class Codes: C08G 18/73 acyclic
• CPC Class Codes: C08G 18/758 containing two or more cycloaliphatic rings

Abstract

This disclosure relates to a controlled-release composition containing a water-swellable linear polymer together with an active agent. The water-swellable linear polymer is obtained by reacting together: (a) a polyethylene oxide of number average molecular weight less than or equal to 4000 g/mol; (b) an aliphatic diol; and (c) a difunctional isocyanate. The ratio of components (a) to (b) to (c) is in the range of 0.01-0.1 to 1 to 1.01-1.1 in terms of equivalent weights. The amount of the polyethylene oxide is less than 50 wt % of the polymer. The polymer has a water swelling percentage of 20-100%.

Claims

1. A controlled-release composition, comprising:

a water-swellable linear polymer together with an active agent, the water-swellable linear polymer obtained by reacting together;

(a) a polyethylene oxide of number average molecular weight less than or equal to 4000 g/mol;

(b) an aliphatic diol; and

(c) a difunctional isocyanate,

wherein the ratio of components (a) to (b) to (c) is in the range of 0.01-0.1 to 1 to 1.01-1.1 in terms of equivalent weights, the amount of the polyethylene oxide is less than 40 wt % of the polymer, and the polymer has a water swelling percentage of 1-100%.

2. The composition of claim 1, wherein the polyethylene oxide is a diol of molecular weight 200 to 4000 g/mol.

3. The composition of claim 1, wherein the aliphatic diol is a C₅ to C₂₀ diol.

4. The composition of claim 3, wherein the aliphatic diol is a C₈ to C₁₅ diol.

5. The composition of claim 1, wherein the aliphatic diol is 1,6-hexanediol, 1,10-decanediol, 1,12-dodecanediol or 1,6-hexadecanediol.

6. The composition of claim 1, wherein the difunctional isocyanate is dicyclohexylmethane-4,4-diisocyanate, diphenylmethane-4,4-diisocyanate, or 1,6-hexamethylene diisocyanate.

7. The composition of claim 1, wherein the amount of the aliphatic diol exceeds 20 wt % of the polymer.

8. The composition of claim 1, wherein the amount of the difunctional isocyanate is 20-50 wt % of the polymer.

9. The composition of claim 1, wherein the composition is in a solid dosage form.

10. The composition of claim 1, wherein the dosage form is a suppository, vaginal ring or pessary, a buccal insert, or a transdermal patch.

11. The composition of claim 1, wherein the dosage form is an implant.

12. The composition of claim 1, wherein the active agent is a pharmaceutically active agent of molecular weight in the range 200 to 20,000 g/mol.

13. The composition of claim 1, wherein the amount of the polyethylene oxide is less than 30 wt % of the polymer.

15. A method of producing the composition of claim 1, comprising melting and drying the polyethylene oxide together with the aliphatic diol at a temperature of 85°

C. to 100°

C. under vacuum; and

then adding the difunctional isocyanate.

14. A controlled-release composition, comprising:

a water-swellable linear polymer together with an active agent, the water-swellable linear polymer obtained by reacting together;

(a) a polyethylene oxide of number average molecular weight less than or equal to 2000 g/mol;

(b) an aliphatic diol; and

(c) a difunctional isocyanate,

wherein the ratio of components (a) to (b) to (c) is in the range of 0.01-0.1 to 1 to 1.01-1.1 in terms of equivalent weights, the amount of the polyethylene oxide is less than 50 wt % of the polymer, and the polymer has a water swelling percentage of 1-100%.