Stabilized insulin preparations and a process for preparation thereof

Claim 1

A process for producing an insulin solution of pH within the range of about pH 6.5-8 stabilized against interface polymerization, stabilization being ascertainable by submitting the insulin solution to shaking and measuring the time before opalescence appears in the insulin solution; said stabilized insulin solution being adapted for parenteral administration by portable or implantable system for continuous infusion of insulin, which process comprises mixing insulin with a phospholipid in a phospholipid to insulin weight ratio of 1:5 to 1:10,000, the phosphlolipid formula being: ##STR2## wherein R' and R" are the same or different each being selected from the group consisting of hydrogen, higher alkylcarbonyl, alkenylcarbonyl, alkadienylcarbonyl, alkatrienylcarbonyl and alkatetraenylcarbonyl, with the proviso that both R' and R" are not hydrogen, and R'" is selected from the group consisting of 2-(trimethylammonio)ethyl, 2-aminoethyl, 2-carboxy-2-aminoethyl, 2,3-dihydroxpropyl and 2,3,4,5,6-pentahydroxycyclohexyl, in the presence of water, and optionally with a zinc salt, a preservative, an agent rendering the insulin solution isotonic, and a buffering agent so as to obtain a concentration of phospholipid of 10-200 μg/ml of stablilized insulin solution, the insulin in solution being essentially outside any liposomes formed by said phospholipid.