Conjugate based systems for controlled insulin delivery
The present disclosure provides conjugates which comprise an insulin molecule conjugated via a conjugate framework to one or more separate ligands that include a first saccharide, and wherein the conjugate framework also comprises a fatty chain (e.g., a C8-30 fatty chain). In certain embodiments, a conjugate is characterized in that, when the conjugate is administered to a mammal, at least one pharmacokinetic (PK) and/or pharmacodynamic (PD) property of the conjugate is sensitive to serum concentration of a second saccharide. In certain embodiments, a conjugate is also characterized by having a protracted PK profile. Exemplary conjugates and sustained release formulations are provided in addition to methods of use and preparation.
1. A conjugate of the formula:
or a pharmaceutically acceptable salt thereof.
2. A method of treating hyperglycemia comprising administering a conjugate of claim 1 , or a pharmaceutically acceptable salt thereof, to a mammalian patient in need thereof.
3. A pharmaceutical composition which comprises a pharmaceutically acceptable carrier and a conjugate of claim 1 , or a pharmaceutically acceptable salt thereof.