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Claims for Patent: 8,067,431

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Claims for Patent: 8,067,431

Title:Chemically modified small molecules
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 bronchoalveolar lavage followed by assaying residual lung material.
Inventor(s): Fishburn; C. Simone (Redwood City, CA), Lechuga-Ballesteros; David (San Jose, CA), Viegas; Tacey (Madison, AL), Kuo; Mei-Chang (Palo Alto, CA), Song; Yuan (Belmont, CA), Gursahani; Hema (Foster City, CA), Leach; Chester (Tijeras, NM)
Assignee: Nektar Therapeutics (San Francisco, CA)
Application Number:12/710,167
Patent Claims: 1. A method of treating a patient in need of an opioid antagonist, comprising: administering to the patient an oral dosage form comprising a compound selected from the group consisting of 6-CH.sub.3--(OCH.sub.2CH.sub.2).sub.5--O-naloxol; 6-CH.sub.3--(OCH.sub.2CH.sub.2).sub.6--O-naloxol; 6-CH.sub.3--(OCH.sub.2CH.sub.2).sub.7--O-naloxol; 6-CH.sub.3--(OCH.sub.2CH.sub.2).sub.8--O-naloxol; and 6-CH.sub.3--(OCH.sub.2CH.sub.2).sub.9--O-naloxol; or a pharmaceutically acceptable salt thereof, wherein the compound is an .alpha.-6 isomer, a .beta.-6 isomer or a mixture of .alpha.-6 and .beta.-6 isomers.

2. The method of claim 1, wherein the compound comprises a mixture of .alpha.-6 and .beta.-6 isomers.

3. The method of claim 2, wherein the compound is 6-CH.sub.3--(OCH.sub.2CH.sub.7).sub.7--O-naloxol or a pharmaceutically acceptable salt thereof.

4. The method of claim 1, wherein the compound is selected from the group consisting of .alpha.-6-CH.sub.3--(OCH.sub.2CH.sub.2).sub.5--O-naloxol; .alpha.-6-CH.sub.3--(OCH.sub.2CH.sub.2).sub.6--O-naloxol; .alpha.-6-CH.sub.3--(OCH.sub.2CH.sub.2).sub.7--O-naloxol; .alpha.-6-CH.sub.3--(OCH.sub.2CH.sub.2).sub.8--O-naloxol; and .alpha.-6-CH.sub.3--(OCH.sub.2CH.sub.2).sub.9--O-naloxol; or a pharmaceutically acceptable salt thereof.

5. The method of claim 4, wherein the compound is .alpha.-6-CH.sub.3--(OCH.sub.2CH.sub.2).sub.7--O-naloxol or a pharmaceutically acceptable salt thereof.

6. The method of claim 1, wherein the compound is selected from the group consisting of .beta.-6-CH.sub.3--(OCH.sub.2CH.sub.2).sub.5--O-naloxol; .beta.-6-CH.sub.3--(OCH.sub.2CH.sub.2).sub.6--O-naloxol; .beta.-6-CH.sub.3--(OCH.sub.2CH.sub.2).sub.7--O-naloxol; .beta.-6-CH.sub.3--(OCH.sub.2CH.sub.2).sub.8--O-naloxol; and .beta.-6-CH.sub.3--(OCH.sub.2CH.sub.2).sub.9--O-naloxol; or a pharmaceutically acceptable salt thereof.

7. The method of claim 1, wherein the compound is .beta.-6-CH.sub.3--(OCH.sub.2CH.sub.3).sub.7--O-naloxol or a pharmaceutically acceptable salt thereof.
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