Lung volume reduction therapy using crosslinked non-natural polymers

A method of sealing an air leak in a lung, comprising the step of administering to a lung of a patient in need thereof a therapeutically effective amount of a hydrogel, wherein said hydrogel is prepared from

• a first non-natural polymer and a first cross-linker;
• said first non-natural polymer consists essentially of a plurality of subunits independently selected from the group consisting of
• wherein independently for each occurrence
• X is —(C(R)2)n—, —(CH2OCH2)nCH2—, —(CH2)n-(cycloalkyl)-CHn—, or —(CH2)n-(aryl)-(CH2)n—;
• R is H or lower alkyl;
• Y is —NHR′, —OH or —SH;
• R′ is hydrogen, NH2, aliphatic, aromatic, heterocyclic, cycloaliphatic or a saturated heterocyclic moiety;
• n is 1-20;
• and
• about 60 mol % to about 99 mol % of the subunits are
• and
• said first cross-linker comprises at least two pendant first electrophilic groups,
• thereby sealing the air leak in the lung.

A method of sealing a bronchopleural fistula in a patient, comprising the step of administering to a patient in need thereof a therapeutically effective amount of a hydrogel, wherein said hydrogel is prepared from

• a second non-natural polymer and a second cross-linker;
• said second non-natural polymer consists essentially of a plurality of subunits independently selected from the group consisting of
• wherein independently for each occurrence
• X is —(C(R)2)n—, —(CH2OCH2)nCH2—, —(CH2)n-(cycloalkyl)-(CH2)n—, or —(CH2)n-(aryl)-(CH2)n—;
• R is H or lower alkyl;
• Z is —C(O)R″, —C(S)R″, halide, —C(NR″)R″, —OP(O)(OR″)2, —OP(O)(OR″)(R″), —OS(O)2(OR″), or —OS(O)2R″;
• R″ is hydrogen, aliphatic, aromatic or heterocyclic;
• n is independently for each occurrence 1-20;
• and
• about 60 mol % to about 99 mol % of the subunits are
• and
• said second cross-linker comprises at least two pendant second nucleophilic groups,
• thereby sealing said bronchopleural fistula.

A method of sealing an air leak in a lung, comprising the step of administering to a lung of a patient in need thereof a therapeutically effective amount of a hydrogel, wherein said hydrogel is prepared from

• a second non-natural polymer and a second cross-linker;
• said second non-natural polymer consists essentially of a plurality of subunits independently selected from the group consisting of
• wherein independently for each occurrence
• X is —(C(R)2)n—, —(CH2OCH2)nCH2—, —(CH2)n-(cycloalkyl)-(CH2)n—, or —(CH2)n-(aryl)-(CH2)n—;
• R is H or lower alkyl;
• Z is —C(O)R″, —C(S)R″, halide, —C(NR″)R″, —OP(O)(OR″)2, —OP(O)(OR″)(R″), —OS(O)2(OR″), or —OS(O)2R″;
• R″ is hydrogen, aliphatic, aromatic or heterocyclic;
• n is independently for each occurrence 1-20;
• and
• about 60 mol % to about 99 mol % of the subunits are
• and
• said second cross-linker comprises at least two pendant second nucleophilic groups,
• thereby sealing the air leak in the lung.