Formulations for amylin agonist peptides

• US 7,312,196 B2
• Filed: 05/31/2002
• Issued: 12/25/2007
• Est. Priority Date: 01/08/1997
• Status: Expired due to Fees

• Current Assignee: Astrazeneca Pharmaceuticals LP (Astrazeneca PLC)
• Original Assignee: Amylin Pharmaceuticals Incorporated (Bristol-Myers Squibb Company)
• Inventors: Stetsko, Gregg, L'Italien, James
• Primary Examiner(s): CHANNAVAJJALA, LAKSHMI SARADA
• Application Number:
  US10/159,779
• Publication Number:
  US 20030092606A1
• Time in Patent Office: 2,034 Days
• Field of Search: 514/12, 514/2, 514/3, 514/866, 514/864, 424/400, 530/324
• US Class Current: 514/5.9
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 38/22 Hormones derived from pro-opiomelanocortin, pro-enkephalin or pro-dynorphin A61K38/33, e.g. corticotropin A61K38/35
• CPC Class Codes: A61K 38/28 Insulins
• CPC Class Codes: A61K 47/02 Inorganic compounds
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/12 Carboxylic acids; Salts or anhydrides thereof
• 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 9/0014 Skin, i.e. galenical aspects of topical compositions non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61K 9/1647 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61K 9/19 lyophilised , i.e. freeze-dried, solutions or dispersions lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

The present invention is concerned with a pharmaceutical formulation comprising an amylin agonist and optionally a buffer, a tonicifier or stabilizer, and a preservative in a container, for example, a vial, prefilled cartridge, prefilled syringe or disposable pen. This formulation may be in liquid, gel, solid or powdered form for delivery, for example, via nasal, pulmonary, oral, sublingual, buccal, transdermal, or parenteral routes. Formulation with biocompatible polymers and release modifiers, such as sugars, can facilitate controlled release after injection, minimizing the number of administrations to a patient. These formulations maintain stability upon storage under refrigerated or room temperature conditions. Such formulations can be further combined with insulin for administration to a patient.

Claims

1. A liquid pharmaceutical formulation comprising about 0.5 to 1.0% (w/v) of an amylin agonist, a pharmaceutically acceptable excipient and a liquid vehicle comprising water or an aqueous/organic solvent mixture or suspension, wherein said formulation comprises about 1.0 to 10% (w/v) of a carbohydrate or a polyhydric alcohol, about 0.02 to 0.5% (w/v) of an acetate, phosphate, citrate or glutamate buffer, and wherein the pH of said formulation is about 3.5 to about 5.0.

2. The formulation of claim 1, wherein the pH of said formulation is about 3.8 to about 4.2.

3. The formulation of claim 1 which is substantially isotonic.

4. The formulation of claim 1 , wherein said amylin agonist is pramlintide.

5. The formulation of claim 1, wherein said polyhydric alcohol is mannitol, sorbitol, inositol, glycerol, xylitol, propylene/ethylene glycol copolymer. PEG 8000, PEG 400, PEG 4000, PEG 200, PEG 1450 or PEG 3350.

6. The formulation of claim 1, wherein said polyhydric alcohol is mannitol.

7. The formulation of claim 1, wherein said carbohydrate is mannose, ribose, trehalose, maltose, glycerol, inositol, lactose, sucrose, fructose, galactose, or arabinose.

8. The formulation of claim 1, wherein said formulation further comprises a surfactant.

9. The formulation of claim 8, wherein said surfactant is polyoxyethylene (20) sorbitan monooleate, 3-[(3-cholamidopropyl) dimethylammonio]1-propanol sulfonate, polyoxyethylene (23) lauryl ether, poloxamer or a non-ionic surfactant.

10. The formulation of claim 8, further comprising a preservative.

11. A method for treating diabetes in a patient in need of such treatment comprising administering a therapeutically effective amount of the formulation of claim 1 to the patient in need of such treatment.

12. The method of claim 11 wherein insulin is admixed with said formulation prior to administration.

13. The method of claim 12 wherein the admixing step is simultaneous, or concerted and sequential with administration.

14. The formulation of claim 1 for administration to a subject, wherein the formulation is administered in the form selected from the group consisting of a parenteral controlled release delivery, oral delivery, a microcapsule delivery, a microsphere, an implant delivery, and a polymer matrix delivery.

16. The formulation of claim 1 formulated for nasal or pulmonary delivery.

17. The formulation of claim 1 formulated for controlled release injectable delivery.

18. The formulation of claim 1 formulated for transdermal delivery.

23. The formulation of claim 1, wherein the amylin agonist is stable for at least 30 days at room temperature.

26. The formulation of claim 1, further comprising a penetration enhancer or a stabilizer.

28. The formulation of claim 1 for administration to a subject, wherein the formulation is administered in a form for controlled release delivery.

15. A liquid suspension formulation comprising about 0.5 to 90% (w/v) of an amylin agonist, about 1.0 to 10% (w/v) of a carbohydrate or a polyhydric alcohol;

and about 0.02 to 0.5% (w/v) of an acetate, phosphate, citrate or glutamate buffer, and a liquid vehicle, wherein the formulation has a pH of about 3.5 to about 5.0.

24. The formulation of claim 15, wherein said amylin agonist is pramlintide.

19. A formulation comprising about 0.5 to 1.0% (w/v) of an amylin agonist, insulin, and a pharmaceutically acceptable emulsifier, wherein said formulation comprises about 0.1 to 10% (w/v) of a carbohydrate or a polyhydric alcohol and wherein the pH of said formulation is about 3.0 to about 7.0.

20. The formulation mixture of claim 19 for use with an insulin pump device.

21. The formulation of claim 19, wherein the emulsifier is an oil.

22. The formulation of claim 19, wherein the insulin is glargine.

25. The formulation of claim 19, wherein said amylin agonist is pramlintide.

27. The formulation of claim 19, further comprising at least one pharmaceutically acceptable excipient selected from the group consisting of a penetration enhancer and a stabilizer.