Exendin Analog Formulations

• US 20080249018A1
• Filed: 04/10/2008
• Published: 10/09/2008
• Est. Priority Date: 01/14/1999
• Status: Abandoned Application

• Current Assignee: Amylin Pharmaceuticals Incorporated (Bristol-Myers Squibb Company)
• Original Assignee: Amylin Pharmaceuticals Incorporated (Bristol-Myers Squibb Company)
• Inventors: YOUNG, Andrew A., KOLTERMAN, Orville G., L'ITALIEN, James J.
• Application Number:
  US12/100,880
• Publication Number:
  US 20080249018A1
• Time in Patent Office: Days
• US Class Current: 514/12
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 38/16 Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof enzyme inhibitors A61K38/005
• CPC Class Codes: A61K 38/26 Glucagons
• CPC Class Codes: A61K 47/60 the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 5/48 of the pancreatic hormones
• CPC Class Codes: C07K 14/57563 Vasoactive intestinal peptide [VIP]; Related peptides
• CPC Class Codes: C07K 14/605 Glucagons

Abstract

Novel formulations containing exendins, exendin agonists and/or exendin analogs are provided

Claims

1. A pharmaceutical formulation which is a liquid dosage gorm suitable for multi-use administration comprising about 0.005% (w/v) to about 0.4% (w/v) of an exendin, an exendin analog or a combination thereof, a buffer, an iso-osmolality modifier, and (bout 0.005% to about 1.0% (w/v) of a preservative selected from the group consisiting of m-cresol, phenol, benzyl alcohol, methyl-, ethyl-, propyl and but-n-paraben and any combination thereof, wherein said formulation has a pH of between about 3.0 and about 7.0 and said exendin is not exendin-4.

2. The formulation of claim 1, said formulation having a pH of between about 4.0 and about 6.0.

3. The formulation of claim 1, wherein said exendin or exendin analog is present at a concentration of between about 0.005% (w/v) and about 0.05%

4. The formulation of claim 1, wherein said buffer is selected from the group consisting of an acetate buffer, a glutamate buffer, a citrate buffer, a phosphate buffer, and any combination thereof.

5. The formulation of claim 1, wherein, said buffer is at a concentration between about 0.02% (w/v) and about 0.5% (w/v).

6. The formulation of claim 1, wherin said iso-osmolality modifier is a carbohydrate, a polyhydric alcohol or a combination thereof, and said iso-osmolality modifier is at a concentration between about 1% (w/v) and 10% (w/v).

7. The formuation of claim 6, wherein said polyhydric alcohol is selected from the group consisting of sorbitol, mannitol, inositol, glycerol, xylitol, polyethylene glycols, and any combination tlereof.

8. The formulation of claim 1, wherein said iso-osmolality modifier is mannitol, sorbitolm, or a combination therof.

9. The formulation of claim 2, wherein said formulation is suitable for administration via injection to achieve a dose of from about 0.1 μ

g/kg to about 0.5 μ

/kg of saId exendin or exendin analog.

15. The formulation of claim 1, wherein the formulation comprises the exendin analog.

16. The formulation of claim 1, wherein the formulation comprises the comprises the amino acId sequence of SEQ ID NO. 41, 42, 43, 44, A5, 46, 47, or 48.

10. A pharmaceutical formulation which is a liquid dosage form suitable for multi-use administration comprising an exendin, an exendin analog or a combination thereof, a buffer, an iso-osmolality modifier, and about 0.005% (w/v) to aboutI 1.0% (w/v) of a preservative selected from the group consisting of m-cresol, phenol, benzyl alcohol, methyl-, ethyl,-, propyl- and butyl-paraben and any combination thereof, wherein said formulation has a pH of betveen about 3.0 and about 6.0 and said exendin is not exendin-4.

11. The formulation of claim 10, wherein said formulation is suitable for a route of administration selected from the group consisiting of:

oral adinstation to achieve a dose of from about 500 μ

g/day to about 12,000 μ

g/day of said exendin or exenidin, analog In a single or divided dose;

pulmonary administration to achieve a dose from about 100 μ

g/day to about 12,000 μ

g/day of said exetdin or exendin analog in a single or divided dose;

sublingual administraton to achieve a dose from about 10 μ

g/day to about 8,000 μ

g/day of said exendin or exerndn analog in a single or divided dose;

nasal administration to achieve a dose from about 10 μ

g/day to about 12,000 μ

g/day of said exendln or eorendn analog if a single or divided dose; and

buccal admstration to achee a dose from about 100 μ

g/day to about 12,000 μ

g/day of said exendin or exendin anialog in a single or divided dose.

17. The formulation of claim 10, wherein the formulation comprises the exendin analog.

18. The formulation of claim 10, wherein the exendin or the exendin analog comprises the amino acid sequence of SEQ ID NO. 42, 4D, 44, 45, 46, 47, or 48.

12. The formulation of claim 26, said formulation having a pH of between about 4:

0 and about 6.0.

13. The formulation of claim 26, wherein said buffer is selected from the group consisting of an acetate buffer, a flutamate bvuffer, a citrate buffer, a phosphate buffer, and any combination thereof.

14. The formulation of claim 26, wherein said buffer is at a concentration between about 0.02% (w/v) and about 0.50 (w/v).