# US 12,214,041 B2 · Polyurethane excipient

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- Number: US 12,214,041 B2
- Document ID: US12214041B2
- Status: Granted
- Kind: B2
- Application number: 17/275,729
- Filed: 2019-09-16
- Published: 2022-02-24
- Granted: 2025-02-04
- Earliest claimed: 2018-09-17
- Assignees: Dsm IP Assets B.V.
- Applicants: DSM IP Assets B.V.
- Inventors: Jennifer Al-Rashid; Jacob Riffey; John Andrew Zupancich
- Web page: https://patentgrep.com/patent/US12214041B2

## CPC

- 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)
- A61K 9/0036: {Devices retained in the vagina or cervix for a prolonged period, e.g. intravaginal rings, medicated tampons, medicated diaphragms}
- A61K 47/32: Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers {, poly(meth)acrylates, or polyvinyl pyrrolidone}
- C08G 18/0895: {Manufacture of polymers by continuous processes (C08G18/0838 takes precedence)}
- C08G 18/12: using two or more compounds having active hydrogen in the first polymerisation step
- C08G 18/3206: {aliphatic}
- C08G 18/4018: {Mixtures of compounds of group C08G18/42 with compounds of group C08G18/48}
- C08G 18/44: Polycarbonates
- C08G 18/4833: {Polyethers containing oxyethylene units}
- C08G 18/73: acyclic
- C08G 18/758: {containing two or more cycloaliphatic rings}
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- C08G: MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS

## Abstract

In an embodiment, a polyurethane comprises the residues of i. an aliphatic diisocyanate, ii. an aliphatic diol comprising a poly(ethylene oxide) moiety, iii. an aliphatic diol comprising a polycarbonate moiety, and iv. a chain extender, wherein the polyurethane has a melting temperature of 140° C. or less and has a weight average molecular weight of from 100,000 to 500,000 g/mol. In an embodiment, the polyurethane is substantially devoid of catalyst. In an embodiment, the polyurethane is formed by reactive extrusion. In an embodiment, a medical device comprises the polyurethane and a bioactive agent. The medical devices, methods, and polyurethanes may exhibit benefits in end-product biostability, drug release profile, health and safety, and processing speed or reproducibility.

## Claims

### Claim 1

A method of forming a medical device comprising a step of extruding at least a portion of the medical device from a melt comprising a polyurethane and a bioactive agent, wherein the resulting medical device comprises:
(a) the polyurethane which comprises residues of:
(i) an aliphatic diisocyanate,
(ii) an aliphatic diol comprising a poly(ethylene oxide) moiety,
(iii) an aliphatic diol comprising a polycarbonate moiety, and
(iv) a chain extender; and
(b) the bioactive agent, wherein
the polyurethane has a melting temperature offset (Tm Offset) of from 95° C. to 140° C. and has a weight average molecular weight of from 100,000 to 500,000 g/mol.

### Claim 2

A method of forming a polyurethane suitable for use in a medical device, the method comprising the steps of:
(a) reactively extruding a composition comprising:
(i) a pre-polymer formed from a pre-polymer composition comprising:
(1) an aliphatic diisocyanate,
(2) an aliphatic diol comprising a poly(ethylene oxide) moiety, and
(3) an aliphatic diol comprising a polycarbonate moiety, and
(ii) a chain extender;
thereby forming a polyurethane, wherein the polyurethane is biostable and the composition is devoid of catalyst, and
(b) post-curing the polyurethane at a temperature of from 55° C. to 90° C., wherein, after post-curing, the polyurethane has a melting temperature offset (Tm Offset) of from 95° C. to 140° C. and has a weight average molecular weight of from 100,000 to 500,000 g/mol.

### Claim 3 (depends on 1)

The method according to claim 1, wherein the polyurethane is formed by reactive extrusion polymerization of a composition comprising:
(i) a pre-polymer formed by polymerizing a pre-polymer composition comprising:
(1) an aliphatic diisocyanate,
(2) an aliphatic diol comprising a poly(ethylene oxide) moiety, and
(3) an aliphatic diol comprising a polycarbonate moiety, and
(ii) a chain extender, wherein
the composition is devoid of catalyst.

### Claim 4 (depends on 2)

The method according to claim 2, wherein the post-curing of the polyurethane according to step (b) is conducted at a temperature of from 55° C. to 90° C.

### Claim 5 (depends on 4)

The method according to claim 4, wherein the post-curing step (b) is conducted for at least 48 hours.

### Claim 6 (depends on 1)

The method according to claim 1, wherein the polyurethane has a melting temperature offset (Tm Offset) of from 110° C. to 130° C.

### Claim 7 (depends on 1)

The method according to claim 1, wherein the polyurethane has a melting temperature onset (Tm Onset) of from 60° C. to 85° C.

### Claim 8 (depends on 6)

The method according to claim 6, wherein the polyurethane has a melting temperature onset (Tm Onset) of from 60° C. to 85° C.

### Claim 9 (depends on 1)

The method according to claim 1, wherein the polyurethane has a weight average molecular weight of at least 150,000 g/mol.

### Claim 10 (depends on 1)

The method according to claim 1, wherein the polyurethane comprises:
(i) from 20 wt % to 45 wt % of the residue of an aliphatic diisocyanate,
(ii) from 3 wt % to 15 wt % of the residue of an aliphatic diol comprising a poly(ethylene oxide) moiety,
(iii) from 30 wt % to 70 wt % of the residue of aliphatic diol comprising a polycarbonate moiety, and
(iv) from 1 wt % to 10 wt % of the residue of a chain extender, wherein
the amounts are based on the total weight of the polyurethane.

### Claim 11 (depends on 1)

The method according to claim 1, wherein the polyurethane consists of:
(i) from 20 wt % to 45 wt % of the residue of an aliphatic diisocyanate,
(ii) from 3 wt % to 15 wt % of the residue of an aliphatic diol comprising a poly(ethylene oxide) moiety,
(iii) from 30 wt % to 70 wt % of the residue of aliphatic diol comprising a polycarbonate moiety, and
(iv) from 1 wt % to 10 wt % of the residue of a chain extender, wherein
the amounts are based on the total weight of the polyurethane.

### Claim 12 (depends on 1)

The method according to claim 1, wherein the aliphatic diol comprising a poly(ethylene oxide) moiety has a weight average molecular weight of from 500 to 2000 g/mol.

### Claim 13 (depends on 1)

The method according to claim 1, wherein the aliphatic diol comprising a polycarbonate moiety has a weight average molecular weight of from 500 to 2000 g/mol.

### Claim 14 (depends on 1)

The method according to claim 1, wherein the polyurethane is devoid of silicone.

### Claim 15 (depends on 1)

The method according to claim 1, wherein the bioactive agent is a drug which is present in the polyurethane in an amount which exceeds a solubility limit of the drug in the polyurethane.

### Claim 16 (depends on 1)

The method according to claim 1, wherein the bioactive agent has a melting temperature that is higher than the melting temperature of the polyurethane.

### Claim 17 (depends on 1)

The method according to claim 1, wherein the bioactive agent has a melting temperature of from 150° C. to 200° C.

### Claim 18 (depends on 1)

The method according to claim 1, wherein the medical device is devoid of catalyst.

### Claim 19 (depends on 2)

The method according to claim 2, wherein the polyurethane has a melting temperature offset (Tm Offset) of from 110° C. to 130° C. and a melting temperature onset (Tm Onset) of from 60° C. to 85° C.