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Neutral Insulin Solutions Physically Stabilized by Addition of Zn 2+
Author(s) -
Brange J.,
Havelund S.,
Hommel E.,
Sørensen E.,
Kühl C.
Publication year - 1986
Publication title -
diabetic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.474
H-Index - 145
eISSN - 1464-5491
pISSN - 0742-3071
DOI - 10.1111/j.1464-5491.1986.tb00809.x
Subject(s) - insulin , random hexamer , immunogenicity , dissociation (chemistry) , regular insulin , human insulin , medicine , monomer , dimer , insulin lispro , endocrinology , biophysics , biochemistry , chemistry , biology , organic chemistry , antibody , immunology , hypoglycemia , polymer
Commercial neutral insulin solutions, all of which contain 2–3 zinc atoms per hexameric unit of insulin, have a relatively limited physical stability when exposed to heat and movement, as for example in insulin infusion pumps. Physical stabilization of neutral insulin solutions has been obtained by addition of two extra Zn 2+ per hexamer of insulin. This addition stabilizes porcine and human neutral solutions equally well and does not affect the chemical stability of the insulin. The stabilization is probably obtained by a further strengthening of the hexameric structure of insulin, so that the formation of insoluble insulin fibrils (via the dissociation into the insulin monomer or dimer) is impeded or prevented. The addition of an extra 2 Zn 2+ has been shown to be without influence on the insulin immunogenicity in rabbits or on the rate of absorption after subcutaneous injection in diabetic patients. It is concluded that neutral insulin solution can be physically stabilized by addition of extra Zn 2+ without affecting other qualities of the insulin preparation including chemical stability, immunogenicity, and duration of action after injection.