Water-swellable polymers

• US 8,628,798 B2
• Filed: 08/10/2012
• Issued: 01/14/2014
• Est. Priority Date: 09/27/2002
• Status: Active Grant

• Current Assignee: Ferring BV (Ferring Holding SA)
• Original Assignee: Ferring BV (Ferring Holding SA)
• Inventors: Halliday, Janet A., Tuominen, Jukka, Livingstone, Mark, Koppenhagen, Frank, Currie, Lilias, Stewart, Sarah
• Primary Examiner(s): Sasan, Aradhana
• Application Number:
  US13/571,596
• Publication Number:
  US 20120302635A1
• Time in Patent Office: 522 Days
• Field of Search: 424/468, 514/560
• US Class Current: 424/468
• CPC Class Codes: A61K 31/215 of carboxylic acids
• 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 9/02 Suppositories; Bougies; Bases therefor; Ovulesapparatus for making A61J3/08; devices for introducing into the body A61M31/00
• CPC Class Codes: C08G 18/6674 with compounds of group C08G18/3203
• CPC Class Codes: C08G 18/758 containing two or more cycloaliphatic rings
• CPC Class Codes: C08G 2210/00 Compositions for preparing hydrogels

Abstract

A water-swellable linear polyurethane polymer is formed by reacting a polyethylene oxide (e.g. PEG 4000 to 35,000), a difunctional compound (e.g. a diamine or diol such as 1,10-decanediol) with a diisocyanate. The ratio of the three components is generally in the range 0.1-1.5 to 1 to 1.1-2.5. The polyurethane is water-swellable in the range 300 to 1700% and soluble in certain organic solvents such as dichloromethane. It can be loaded with pharmaceutically active agents, particularly of high molecular weight, to produce controlled release compositions, such as pessaries etc.

Claims

1. A controlled release composition, comprising a cross-linked polyurethane polymer loaded with misoprostol;

wherein the cross-linked polyurethane polymer is formed from a polyethylene glycol, a triol and a diisocyanate and the composition comprises 200 μ

g of misoprostol.

2. The composition of claim 1, wherein the cross-linked polyurethane polymer is formed from PEG8000, hexanetriol and dicyclohexylmethane-4.4-diisocyanate.

3. The composition of claim 2, wherein the ratio of PEG8000:

hexanetriol;

dicyclohexylmethane-4.4-diisocyanate is 1.0;

1.2;

2.8.

4. The composition of claim 2, wherein the ratio of PEG8000:

hexanetriol;

dicyclohexylmethane-4.4-diisocyanate is 0.8;

1.0;

2.3.

5. The composition of claim 1, wherein the composition is in the form of a pessary.

6. The composition of claim 5, wherein the composition has been dried in a vacuum oven at room temperature for at least 24 hours.

7. The composition of claim 6, wherein substantially 80% of the misoprostol in the composition is released after 480 minutes in water at 37°

C.

8. The composition of claim 6, wherein the composition has a misoprostol release rate of 4.507 minute⁻

0.5.

9. The composition of claim 6, wherein the composition is a pharmaceutical composition.

10. A method of making a composition, comprising

dissolving misoprostol in a 25% w/w ethanol aqueous solution,

immersing a cross-linked polyurethane polymer in the solution, and

removing the polymer from the solution to form a composition containing a cross-linked polyurethane polymer loaded with misoprostol;

wherein the cross-linked polyurethane polymer is formed from a polyethylene glycol, a triol and a diisocyanate and the composition comprises 200 μ

g of misoprostol.

11. The method of claim 10, further comprising drying the composition after the removing step.

12. The method of claim 10, wherein the cross-linked polyurethane polymer is immersed in the solution for 16-24 hours at 4°

C.