GLUCAGON-LIKE PEPTIDE-2 AND ITS THERAPEUTIC USE
First Claim
1. A pharmaceutical composition, comprising a GLP-2 peptide selected from a vertebrate GLP-2 or an intestinotrophic analog of a vertebrate GLP-2 which analog differs from a vertebrate GLP-2 in that it incorporates at least one amino acid addition, deletion, substitution or an amino acid with an N- or C-terminal amino acid blocking group, and a pharmaceutically acceptable carrier.
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Abstract
Glucagon-like peptide 2, a product of glucagon gene expression, and analogs of glucagon-like peptide 2, have been identified as gastrointestinal tissue growth factors. Their effects on the growth of small bowel and pancreatic islets are described. Their formulation as a pharmaceutical, and their therapeutic use in treating disorders of the bowel, are described.
14 Citations
17 Claims
- 1. A pharmaceutical composition, comprising a GLP-2 peptide selected from a vertebrate GLP-2 or an intestinotrophic analog of a vertebrate GLP-2 which analog differs from a vertebrate GLP-2 in that it incorporates at least one amino acid addition, deletion, substitution or an amino acid with an N- or C-terminal amino acid blocking group, and a pharmaceutically acceptable carrier.
- 12. A pharmaceutically acceptable, acid addition salt of a GLP-2 peptide.
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14. A method useful to identify novel intestinotrophic peptides, comprising the steps of:
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a) obtaining an analog of an intestinotrophic vertebrate GLP-2 peptide, the analog having at least one amino acid substitution, deletion, addition, or an amino acid with a blocking group; b) treating a mammal with said analog using a regimen capable of eliciting an intestinotrophic effect when utilized for rat GLP-2; and c) determining the effect of said analog on small bowel weight and/or on the crypt plus villus height and/or pancreatic islet size relative to a mock treated control mammal, whereby said intestinotrophic peptide is identified as an analog which elicits an increase in said weight and/or said height and/or said size.
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15. A method for treating a patient to restore gastrointestinal tissue, the gastrointestinal tissue selected from pancreatic islets and bowel tissue, which comprises the step of implanting in said patient cells that have been conditioned by growth in a GLP-2 peptide-containing medium.
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16. A method for treating a gastrointestinal disease,
wherein the gastrointestinal disease is selected from the group consisting of ulcers, digestion disorders, malabsorption syndromes, short-gut syndrome, cul-de-sac syndrome, inflammatory bowel disease, celiac sprue, tropical sprue, hypogammaglobulinemic sprue, enteritis, regional enteritis (Crohn'"'"'s disease), small intestinal damage due to toxic or other chemotherapeutic agents, and short bowel syndrome, and wherein the method comprises administering to a patient having the gastrointestinal disease a therapeutically effective amount of a GLP-2 or a GLP-2 analog together with a pharmaceutically acceptable carrier to reduce a pathological effect or symptom of the gastrointestinal disease.
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17. A method for treating diabetes, comprising administering to a patient having diabetes a therapeutically effective amount of a GLP-2 or a GLP-2 analog together with a pharmaceutically acceptable carrier to increase the levels of insulin in the patient.
Specification