Insulinotropic hormone
AssigneeThe General Hospital Corporation
InventorJoel F. Habener
Life of this patent
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Abstract
Derivatives of glucagon-like peptide I (GLP-1) have been found to have insulinotropic activity. The invention pertains to such derivatives, and to the use of such derivatives as a potential therapy for Diabetes Mellitus.
Claims21
A molecule selected from the group consisting of:
- (A) a peptide having the amino acid sequence:
- His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala -Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-X
- wherein X is selected from the group consisting of:
- (a) Lys, and
- (b) Lys-Gly;
- and
- (B) a derivative of said peptide (A), wherein said derivative is selected from the group consisting of:
- (1) a pharmaceutically acceptable acid addition salt of said peptide;
- (2) a pharmaceutically acceptable carboxylate salt of said peptide;
- (3) a pharmaceutically acceptable lower alkyl ester of said peptide;
- and,
- (4) a pharmaceutically acceptable amide of said peptide wherein said pharmaceutically acceptable amide is selected from the group consisting of amide, lower alkyl amide and lower dialkyl amide;
- wherein said molecule is substantially free of natural contaminants, and has an insulinotropic activity which exceeds the insulinotropic activity of GLP-1 (1-36) or GLP-1 (1-37).
An insulinotropic composition which comprises an insulinotropic molecule in an amount effective for the treatment of maturity onset diabetes mellitus, said molecule being selected from the group consisting of:
- (A) a peptide having the amino acid sequence:
- His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala -Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-X
- wherein X is selected from the group consisting of:
- (a) Lys, and
- (b) Lys-Gly;
- and
- (B) a derivative of said peptide (A), wherein said derivative is selected from the group consisting of:
- (1) a pharmaceutically acceptable acid addition salt of said peptide;
- (2) a pharmaceutically acceptable carboxylate salt of said peptide;
- (3) a pharmaceutically acceptable lower alkyl ester of said peptide;
- and,
- (4) a pharmaceutically acceptable amide of said peptide wherein said pharmaceutically acceptable amide is selected from the group consisting of amide, lower alkyl amide and lower dialkyl amide;
- wherein said molecule has an insulinotropic activity which exceeds the insulinotropic activity of GLP-1 (1-36) or GLP-1 (1-37);
- said molecule combined in admixture with a suitable pharmaceutically acceptable carrier.
A method for treating maturity onset diabetes mellitus in an individual in need of such treatment, said method comprising providing an amount of an insulinotropic molecule sufficient to treat said diabetes;
- wherein said molecule is selected from the group consisting of:
- (A) a peptide having the amino acid sequence:
- His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala -Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-X
- wherein X is selected from the group consisting of:
- (a) Lys, and
- (b) Lys-Gly;
- and
- (B) a derivative of said peptide (A), wherein said derivative is selected from the group consisting of:
- (1) a pharmaceutically acceptable acid addition salt of said peptide;
- (2) a pharmaceutically acceptable carboxylate salt of said peptide;
- (3) a pharmaceutically acceptable lower alkyl ester of said peptide;
- and,
- (4) a pharmaceutically acceptable amide of said peptide wherein said pharmaceutically acceptable amide is selected from the group consisting of amide, lower alkyl amide and lower dialkyl amide;
- wherein said molecule has an insulinotropic activity which exceeds the insulinotropic activity of GLP-1 (1-36) or GLP-1 (1-37);
- said molecule combined in admixture with a suitable pharmaceutically acceptable carrier.
Dependencies are inferred from the claim text.