Pharmaceutical compositions of insulin drug-oligomer conjugates and methods of treating diseases therewith

A method of treating an insulin deficiency in a subject in need of such treatment, said method comprising administering to the subject a pharmaceutical composition comprising (a) a therapeutically effective amount of an insulin drug-oligomer conjugate that comprises an insulin drug covalently coupled to an oligomeric moiety;

• (b) a fatty acid component comprising a fatty acid;
• and (c) a bile salt component comprising a bile salt, wherein the fatty acid component and the bile salt component are present in a weight ratio of between 1:5 and 5:1, wherein the fatty acid component is present in an amount sufficient to lower the precipitation point of the bile salt compared to a precipitation point of the bile salt if the fatty acid component were not present in the pharmaceutical composition, and wherein the fatty acid component is present in an amount sufficient to lower the solubility point of the fatty acid compared to a solubility point of the fatty acid if the bile salt were not present in the pharmaceutical composition.

A method of treating an insulin deficiency in a subject in need of such treatment, said method comprising administering to the subject a pharmaceutical composition comprising (a) a therapeutically effective amount of an insulin drug-oligomer conjugate that comprises an insulin drug covalently coupled to an oligomeric moiety;

• (b) a bile salt component comprising a bile salt;
• and (c) a fatty acid component comprising a fatty acid, wherein the fatty acid component and the bile salt component are present in a weight ratio of between 1:5 and 5:1, and wherein the fatty acid component is present in a first amount such that, at the precipitation point of the bile salt, the bile salt precipitates as first bile salt particles that, upon a return to a pH above the precipitation point of the bile salt, re-solubilize more quickly than second bile salt particles that would have precipitated if the fatty acid component were not present in the composition.

A method of treating an insulin deficiency in a subject in need of such treatment, said method comprising administering to the subject a pharmaceutical composition comprising (a) a therapeutically effective amount of an insulin drug-oligomer conjugate that comprises an insulin drug and an oligomeric moiety;

• (b) between 0.1 and 15% (w/v) of a fatty acid component;
• and (c) between 0.1 and 15% (w/v) of a bile salt component, wherein the fatty acid component and the bile salt component are present in a weight to weight ratio of between 1:5 and 5:1.

A method of providing a pharmaceutical composition, said method comprising:

• selecting an amount of a bile salt to include in the composition based on the ability of the bile salt to increase the solubility of a fatty acid component when the composition has a pH of 8.5 or less.

A method of providing a pharmaceutical composition, said method comprising:

• selecting an amount of a fatty acid to include in the composition based on the ability of the fatty acid to lower the precipitation point of a bile salt component in the composition to a pH of 5.5 or less.

A method of providing a pharmaceutical composition, said method comprising:

• selecting an amount of a fatty acid to include in the composition based on the ability of the fatty acid to alter the precipitation characteristics of a bile salt component in the composition.