Glycosylated insulin derivatives

• US 4,478,746 A
• Filed: 02/06/1984
• Issued: 10/23/1984
• Est. Priority Date: 11/17/1982
• Status: Expired due to Term

• Current Assignee: University of Utah (State of Utah)
• Original Assignee: University of Utah (State of Utah)
• Inventors: McRea, James C., Kim, Wan S., Jeong, Seo Y.
• Primary Examiner(s): WADDELL, FREDERICK
• Application Number:
  US06/532,697
• Time in Patent Office: 260 Days
• Field of Search: 424/178, 260/112.7
• US Class Current: 530/303
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61P 3/06 Antihyperlipidemics
• CPC Class Codes: C07H 15/203 Monocyclic carbocyclic rings other than cyclohexane rings; Bicyclic carbocyclic ring systems
• CPC Class Codes: C07K 14/62 Insulins
• CPC Class Codes: H01B 11/04 with pairs or quads mutually positioned to reduce cross-talk
• CPC Class Codes: H01B 13/04 Mutually positioning pairs or quads to reduce cross-talk

Abstract

Synthesized succinyl and glutaryl glucosamines, p-(succinylamido)-phenyl-α-D-gluco- and mannopyranosides, p-(glutarylamido)-phenyl-α-D-gluco- and mannopyranosides and p-(isothiocyanotophenyl)-α-D-gluco- and mannopyranosides are reacted with insulin to form corresponding glycosylated insulins containing from 1 to 3 glycosyl groups per insulin molecule. The novel glycosylated insulins resist aggregation and shown significant activity in depressing blood sugar levels.

Claims

1. A glycosylated insulin having the formula ##STR24## wherein X and Z are different and are selected from the group consisting of --H and --OH, n is an integer of 2 to 6 and m is an integer of 1 to 3, and wherein each glycosyl group is attached to the insulin by an amide linkage through one or more of the α

-amino groups of the A-1 glycine, B-1 phenylalanine or ε

-amino group of the B-29 lysine moieties of the insulin molecule.

2. A glycosylated insulin according to claim 1 wherein Z is --H, X is --OH and n is 2.

3. A glycosylated insulin according to claim 1 wherein Z is --H, X is --OH and n is 3.

4. A glycosylated insulin according to claim 1 wherein Z is --OH, X is --H and n is 2.

5. A glycosylated insulin according to claim 1 wherein Z is --OH, X is --H and n is 3.