Use of dipeptidyl peptidase IV effectors for lowering the blood glucose level in mammals

• US 6,303,661 B1
• Filed: 10/06/1998
• Issued: 10/16/2001
• Est. Priority Date: 04/25/1996
• Status: Expired due to Term

• Current Assignee: Royalty Pharma Collection Trust (Royalty Pharma Plc)
• Original Assignee: Probiodrug AG
• Inventors: Demuth, Hans-Ulrich, Pederson, Ray A., Schmidt, Joem, McIntosh, Christopher H. S., Pauly, Robert P., Rosche, Fred
• Primary Examiner(s): BORIN, MICHAEL L
• Application Number:
  US09/155,833
• Time in Patent Office: 1,106 Days
• Field of Search: 424/94.63, 514/19, 514/183, 514/866
• US Class Current: 514/6.9
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/40 having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
• CPC Class Codes: A61K 31/401 Proline; Derivatives thereof, e.g. captopril
• CPC Class Codes: A61K 31/426 1,3-Thiazoles
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 3/08 for glucose homeostasis pancreatic hormones A61P5/48
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 3/12 for electrolyte homeostasis
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/50 for increasing or potentiating the activity of insulin

Abstract

Novel therapeutic regimens are provided which comprise the administration of therapeutically effective amounts of an inhibitor to dipeptidyl peptidase (DP-IV) or enzymes of similar activity whereby their ability to degrade the incretins, GLP-1 and GIP, is reduced. As a result hyperglycemia, such as that accompanying food intake may be reduced due to improved insulin release. A preferred therapeutic regimen amongst a number of routes of administration and inhibitors that may be used comprises the oral administration of isoleucyl thiazolidine.

Claims

1. A method for lowering elevated blood glucose levels in mammals resulting from food intake comprising administering at least one oral administration of a therapeutically effective amount of at least one inhibitor of Dipeptidyl Peptidase (DP IV) or of DP IV-like enzyme activity.

2. The method according to claim 1, wherein said at least one inhibitor is selected from the group consisting of alanyl pyrrolidine, isoleucyl thiazolidine, and N-valyl prolyl, O-benzoyl hydroxylamine.

3. The method according to claim 1, wherein said at least one inhibitor is administered in combination with at least one carrier substance.

4. The method according to claim 1, wherein said at least one inhibitor is administered in multiple administrations.

5. The method according to claim 1, wherein said amount is between 1.0 mg to 10.0 mg per kilogram of the inhibitor compound.

6. The method according to claim 1, wherein the mammals demonstrate clinically inappropriate basal and post-prandial hyperglycemia.

7. The method according to claim 1, wherein the administration is for the prevention or alleviation of pathological abnormalities of metabolism of mammals such as glucosuria, hyperlipidaemia, metabolic acidosis and Diabetes mellitus.

8. A method for lowering elevated blood glucose levels in mammals resulting from food intake comprising the administration of a therapeutically effective amount of an inhibitor of DP-IV enzyme activity comprising isoleucyl thiazolidine.

9. A method for lowering elevated blood glucose levels in mammals resulting from food intake comprising the oral administration of a therapeutically effective amount of an inhibitor of DP-IV enzyme activity selected from the group consisting of alanyl pyrrolidine and isoleucyl thiazolidine.