Insulinotropic hormone

• US 5,120,712 A
• Filed: 06/01/1990
• Issued: 06/09/1992
• Est. Priority Date: 05/05/1986
• Status: Expired due to Term

• Current Assignee: The General Hospital Corporation (Mass General Brigham, Inc.)
• Original Assignee: The General Hospital Corporation (Mass General Brigham, Inc.)
• Inventors: Habener, Joel
• Primary Examiner(s): Lee, Lester L.
• Assistant Examiner(s): CHAN, Y CHRISTINA
• Application Number:
  US07/532,113
• Time in Patent Office: 739 Days
• Field of Search: 530/324, 530/303, 530/308, 514/12, 514/866
• US Class Current: 514/5.9
• CPC Class Codes: A61K 38/26 Glucagons
• CPC Class Codes: C07K 14/605 Glucagons

Abstract

A fragment of glucagon-like peptide I (GLP-1) has been found to be an insulinotropic hormone. This insulinotropic hormone comprises amino acid residues 7-37 of GLP-1. The insulinotropic hormone is useful as a potential therapy for Diabetes Mellitus.

Claims

1. A molecule selected from the group consisting of:

(a) a peptide having the amino acid sequence;

##STR2## 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).

2. The molecule of claim 1 which is said peptide (a).

3. The molecule of claim 1 which is said derivative (b) of said peptide (a).

4. The molecule of claim 3, wherein said amide is selected from the group consisting of a lower alkyl amide and a lower dialykyl amide.

5. An insulintropic composition which comprises an insulinotropic molecule in an amount effective to stimulate insulin secretion in a patient for treatment of maturity onset diabetes mellitus, said molecule being selected from the group consisting of:

(a) a peptide having the amino acid sequence;

##STR3## 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.

6. The insulinotropic composition of claim 5, wherein said insulinotropic molecule is said peptide (a).

7. The insulinotropic composition of claim 5, wherein said insulinotropic molecule is said derivative (b) of said peptide (a).

8. A method for treating maturity onset diabetes mellitus in an individual in need of such treatment, wherein said method comprises providing an amount of an insulintropic molecule sufficient to treat said diabetes;

wherein said molecule is selected from the group consisting of;

(a) a peptide having the amino acid sequence;

##STR4## 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).

9. The method for treating maturity onset diabetes mellitus of claim 8, wherein said insulinotropic molecule is said peptide (a).

10. The method for treating maturity onset diabetes mellitus of claim 8, wherein said insulinotropic molecule is said derivative (b) of said peptide (a).