Nylon-3 co-polymers and synthetic lung surfactant compositions containing same

US9925213B2 · kind B2 · utility

Assignees

• Wisconsin Alumni Research Foundation · US
• Northwestern University · US

Inventors

• Samuel H. Gellman · Madison, US
• Shannon S. Stahl · Madison, US
• Brendan P. Mowery · San Marcos, US
• Annelise E. Barron · Palo Alto, US
• Michelle Dohm · Palos Park, US

Key dates

• Filing date: May 1, 2015
• Grant date: Mar 27, 2018
• Expiry date: May 1, 2035

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C08L77/02
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

Non-natural oligomers have recently shown promise as functional analogs of lung surfactant proteins B and C (SP-B and SP-C), two helical and amphiphilic proteins that are critical for normal respiration. The generation of non-natural mimics of SP-B and SP-C has previously been restricted to step-by-step, sequence-specific synthesis, which results in discrete oligomers that are intended to manifest specific structural attributes. Presented herein an alternative approach to SP-B mimicry that is based on sequence-random copolymers containing cationic and lipophilic subunits. These materials, members of the nylon-3 family, are prepared by ring-opening polymerization of β-lactams. The best of the nylon-3 polymers display promising in vitro surfactant activities in a mixed lipid film. Pulsating bubble surfactometry data indicate that films containing the most surface-active polymers attain adsorptive and dynamic-cycling properties that surpass those of discrete peptides intended to mimic SP-B. Attachment of an N-terminal octadecanoyl unit to the nylon-3 copolymers affords further improvements by reducing the percent surface area compression to reach low minimum surface tension.