GLP-1 formulations

• US 6,358,924 B1
• Filed: 06/01/2000
• Issued: 03/19/2002
• Est. Priority Date: 12/05/1997
• Status: Expired due to Term

• Current Assignee: Eli Lilly and Company
• Original Assignee: Eli Lilly and Company
• Inventors: Hoffmann, James Arthur
• Primary Examiner(s): Russel, Jeffrey E.
• Application Number:
  US09/585,181
• Time in Patent Office: 656 Days
• Field of Search: 514/12, 514/21, 530/324, 530/399
• US Class Current: 514/6.9
• CPC Class Codes: A61K 38/26 Glucagons
• CPC Class Codes: A61K 47/186 Quaternary ammonium compounds, e.g. benzalkonium chloride or cetrimide
• CPC Class Codes: A61K 47/20 containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
• CPC Class Codes: A61K 47/26 Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• CPC Class Codes: A61K 47/28 Steroids, e.g. cholesterol, bile acids or glycyrrhetinic acid
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61K 9/08 Solutions composition of solutions A61K47/00
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Abstract

Methods and formulations are presented that provide for a) the oral absorption of GLP-1 peptides that bind surfactants; and b) long-term storage of formulations containing these peptides. For example, a GLP-1/DSS complex is administered orally instead of parenterally, which is much more convenient for, and facilitates compliance with diabetic patients and persons with other GLP-1 treated conditions.

Claims

1. A stable pharmaceutical formulation comprising a GLP-1 compound selected from the group consisting of:

GLP-1, GLP-1 analogs, and GLP-1 derivatives wherein the GLP-1 compound can bind to the GLP-1 receptor, complexed with an anionic surfactant selected from the group consisting of docusate sodium, docusate calcium, docusate potassium, sodium dodecyl sulfate, sodium caprylate, sodium cholate, sodium deoxycholate, sodium taurocholate, and sodium glycocholate and a preservative wherein the stable formulation is a solution and has a pH between about 6.5 and about 9.0.

2. The formulation of claim 1, wherein the GLP-1 compound is a GLP-1 derivative.

3. The formulation of claim 2, wherein the GLP-1 derivative is a GLP-1 analog having an acylated lysine ε

-amino group.

4. The formulation of claim 1, wherein the GLP-1 compound has an amino acid sequence selected from the group consisting of SEQ ID NO:

1, SEQ ID NO;

4, and SEQ ID NO;

5, or pharmaceutically acceptable salts thereof.

5. The formulation of claim 1 further comprising an isotonicity agent.

6. The formulation of claim 1 wherein the anionic surfactant is docusate sodium.

7. The formulation of claim 6 wherein the GLP-1 compound is complexed with docusate sodium and has an altered secondary structure compared to the uncomplexed GLP-1 compound.

8. The formulation of claim 7 wherein the GLP-1 compound comprises the sequence of SEQ ID NO:

5.

9. The formulation of claim 1 wherein the molar ratio of anionic surfactant to GLP-1 compound is between about 0.1:

1 and about 50;

1.

10. The formulation of claim 9 wherein the molar ratio is about 2:

1.

11. A method of treating a person having a condition for which administration of a GLP-1 compound is indicated, said method comprising administering a pharmacologically effective amount of a formulation of claim 1.