| 摘要 |
Compositions and methods are disclosed for treating a patient with insuli n, wherein a composition in a form suitable for nasal delivery to a patient comprises a therapeutically effective amount of insulin, a permeation enhanc er, a liquid carrier, and an acid present in said composition in an amount s ufficient to provide an acidic pH, but not greater than a pH of 4.5, said ac id being selected from the group consisting of: monovalent inorganic acid(s) , sulfuric acid, and acetic acid. Preferably the composition is essentially- free of citrate(s) and essentially-free of phosphate(s). The composition bei ng thus designed with the intent to provide a composition that is essentiall y-free of fibrilliform (or beta-sheet) insulin polymorphs. Also disclosed ar e pharmaceutical compositions for nasal administration to humans, or to warm -blooded animals, comprising: (A) a therapeutically effective amount of insu lin; (B) a permeation enhancer; and (C) a liquid carrier; the compositions b eing further comprised of, or characterized by, any, or each, of: (D) a comb ination of non-ionic surfactants; wherein the combination of non-ionic surfa ctants comprises: (i) at least one fatty acid ester of a sugar or sugar alco hol and (ii) at least one pegylated fatty acid ester of a sugar or sugar alc ohol; (E) an acidic pH, but no greater than a pH of 4.5; and (F) an osmolali ty of < 200 mOsmol/Kg H2O.
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