Chemically modified small molecules

Patent metadata

Field	Value
Publication number	US-11129794-B2
Application number	US-201816020773-A
Country	US
Kind code	B2
Filing date	Jun 27, 2018
Priority date	Dec 16, 2003
Publication date	Sep 28, 2021
Grant date	Sep 28, 2021

Abstract

Methods of modifying the rate of systemic absorption of a drug administered to a subject by a pulmonary route, the method comprising covalently conjugating a hydrophilic polymer to a drug, wherein the drug has a half-life of elimination from the lung of less than about 180 minutes, to form a drug-polymer conjugate, wherein the drug-polymer conjugate has a net hydrophilic character and a weight average molecular weight of from about 50 to about 20,000 Daltons, and wherein the half-life of elimination from the lung of the drug-polymer conjugate is at least about 1.5-fold greater than the half-life of elimination from the lung of the drug, wherein the half-life of elimination from the lung is measured by bronchioalveolar lavage followed by assaying residual lung material.

First claim

What is claimed is:

1. A pharmaceutical composition for pulmonary administration via inhalation, the composition comprising an anti-infective drug conjugate comprising ciprofloxacin covalently attached to a single linear polyethylene glycol (PEG) via a hydrolytically stable linkage, wherein the weight average molecular weight of the polyethylene glycol is from 1000 Daltons to 3500 Daltons.

2. The pharmaceutical composition according to claim 1 comprising at least one pharmaceutically acceptable excipient.

3. The pharmaceutical composition according to claim 1 , in liquid form.

4. The pharmaceutical composition according to claim 1 , in the form of a dry powder.

5. An aerosol comprising the pharmaceutical composition according to claim 1 .

6. The pharmaceutical composition according to claim 1 , in an inhaler device.

7. The pharmaceutical composition according to claim 1 , wherein the composition comprises particles having a mass median aerodynamic diameter (MMAD) of less than 10 microns.

8. The pharmaceutical composition according to claim 1 , wherein the composition comprises particles having a MMAD of less than 5 microns.

9. A spray-dried pharmaceutical composition of claim 1 .

10. A unit dosage form comprising the pharmaceutical composition according to claim 1 .

11. The pharmaceutical composition according to claim 4 in an inhaler device.

12. The pharmaceutical composition of claim 1 , wherein the anti-infective drug conjugate has a half-life of elimination from the lung that ranges from is at least 2-fold greater to 100-fold greater than the half-life of elimination from the lung of unconjugated ciprofloxacin when measured in rats following intratracheal administration, wherein the half-life of elimination from the lung is measured by bronchoalveolar lavage followed by assaying residual lung material.

13. The pharmaceutical composition of claim 12 , wherein the half-life of elimination from the lung of the anti-infective drug conjugate ranges from at least 10-fold greater to 100-fold greater than the half-life of elimination from the lung of unconjugated ciprofloxacin.

14. The pharmaceutical composition of claim 1 , wherein the polyethylene glycol comprises a methoxy end-capping group.

Assignees

• Nektar Therapeutics

Inventors

• Jude-Fishburn C Simone
• Lechuga-Ballesteros David
• Viegas Tacey X
• Kuo Mei-Chang
• Gursahani Hema
• Leach Chester
• Song Yuan

Classifications

• A61K47/60 Primary

  the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol · CPC title

• C07C41/24

  by elimination of halogens, e.g. elimination of HCl · CPC title

• A61K9/007 Primary

  Pulmonary tract; Aromatherapy · CPC title

• A61K31/485

  Morphinan derivatives, e.g. morphine, codeine · CPC title

• A61K31/167

  having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol · CPC title