Injectable
insulin formulations that are capable of modifying the amount of
insulin released based on the patient's tissue glucose levels, methods for making and using these formulations are described herein. The formulation may be administered via subcutaneous, intradermal or intramuscular administration. In one preferred embodiment, the formulations are administered via
subcutaneous injection. The formulations contain
insulin, an
oxidizing agent or
enzyme and a
reducing agent or
enzyme, a
diluent and optionally one or more thickening agents. If a
thickening agent is present in the formulation, the
thickening agent increases the
viscosity of the formulation following administration. Preferably the formulation contains an insulin, a
diluent,
glucose oxidase and
peroxidase. Following administration to a patient, the insulin is released from the formulations as a function of the patient's tissue glucose level, which in turn maintains the patient's blood glucose level within an optimum range. The formulation is often referred to as a “smart” formulation since it modifies its release rate of insulin according to the patient's needs at a particular time. In a preferred embodiment, the formulation is designed to release insulin into the
systemic circulation over time with a basal release profile following injection in a patient. In another embodiment, the formulation is designed to release insulin into the
systemic circulation over time with a non-basal release profile following injection in a patient, such as a regular
human insulin release profile or a prandial release profile.