Posaconazole polymer conjugates and methods of treatment using posaconazole and polymer conjugates thereof

• US 7,625,898 B2
• Filed: 01/15/2008
• Issued: 12/01/2009
• Est. Priority Date: 01/16/2007
• Status: Expired due to Fees

• Current Assignee: Belrose Pharma, Inc.
• Original Assignee: Enzon Pharmaceuticals Inc. (Icahn Associates Holding LLC)
• Inventors: Zhao, Hong
• Primary Examiner(s): Silverman; Eric E.
• Application Number:
  US12/014,391
• Publication Number:
  US 20080171013A1
• Time in Patent Office: 686 Days
• Field of Search: None
• US Class Current: 514/247
• CPC Class Codes: A61K 31/496 Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• CPC Class Codes: A61K 31/74 Synthetic polymeric materials
• CPC Class Codes: A61K 47/60 the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
• CPC Class Codes: A61P 31/10 Antimycotics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/04 specific for metastasis
• CPC Class Codes: C08G 65/331 containing oxygen cyclic ether compounds C08G65/26
• CPC Class Codes: C08G 65/3318 heterocyclic
• CPC Class Codes: C08G 65/3326 aromatic
• CPC Class Codes: C08G 65/33317 heterocyclic
• CPC Class Codes: C08G 65/33396 having oxygen in addition to nitrogen
• CPC Class Codes: C08L 2203/02 for biomedical use

Abstract

Improved posaconazole-based compositions and methods of treating and preventing fungal infections, cancer or metastatic diseases are disclosed. In preferred aspects, the conjugates are PEG-posaconazole conjugates in which the PEG has a molecular weight of about 20,000 daltons.

Claims

1. A polymeric conjugate having Formula (III):

2. A method of preparing a polymeric conjugate of claim 1, comprising

a) reacting a compound of the structure

3. The method of claim 1, wherein the base is 4-dimethylaminopyridine (DMAP) and the coupling agent is 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (EDC).

4. A pharmaceutical composition comprising an effective amount of the polymeric conjugate of claim 1 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.

5. A method of treating or preventing fungal infections in a mammal, comprising administering an anti-fungally effective amount of a polymeric conjugate of claim 1 to a mammal in need thereof.

6. The method of claim 5, wherein the polymeric conjugate is administered parenterally.

7. The method of claim 5, wherein the amount of posaconazole administered to the mammal is from about 10 to about 2,000 mg per day.

8. The method of claim 5, wherein the amount of posaconazole administered to the mammal is from about 50 to about 800 mg per day.

9. The method of claim 5, wherein the amount of posaconazole administered to the mammal is from about 5 to about 50 mg/kg/day.

10. The method of claim 5, wherein the amount of posaconazole administered is an amount effective to produce an arithmetic mean steady state average maximum plasma concentration of posaconazole that exceeds the majority of the Minimum Inhibitory Concentrations needed to kill 90% (“

MICs₉₀”

) of the clinically relevant pathogenic fungi.