Pharmaceutical composition comprising a GLP-1 agonist, an insulin and methionine

• US 10,029,011 B2
• Filed: 11/11/2010
• Issued: 07/24/2018
• Est. Priority Date: 11/13/2009
• Status: Active Grant

• Current Assignee: Sanofi-Aventis Deutschland GmbH (Sanofi )
• Original Assignee: Sanofi-Aventis Deutschland GmbH (Sanofi )
• Inventors: Hagendorf, Annika, Hauck, Gerrit, Mueller, Werner, Schoettle, Isabell, Siefke-Henzler, Verena, Tertsch, Katrin
• Primary Examiner(s): Ahmed, Hasan
• Assistant Examiner(s): D' AMBROSIO, THEA
• Application Number:
  US13/509,542
• Publication Number:
  US 20120295846A1
• Time in Patent Office: 2,812 Days
• Field of Search: None
• 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 38/26 Glucagons
• CPC Class Codes: A61K 38/28 Insulins
• 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 47/183 Amino acids, e.g. glycine, EDTA or aspartame
• CPC Class Codes: A61K 47/20 containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
• 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: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• 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 5/50 for increasing or potentiating the activity of insulin
• CPC Class Codes: A61P 7/12 Antidiuretics, e.g. drugs for diabetes insipidus ADH A61P5/10
• CPC Class Codes: C07K 14/605 Glucagons
• CPC Class Codes: C07K 14/62 Insulins

Abstract

A liquid composition comprising a GLP-1 agonist or/and a pharmacologically tolerable salt thereof, an insulin or/and a pharmacologically tolerable salt thereof, and, optionally, at least one pharmaceutically acceptable excipient, wherein the composition comprises methionine, as add-on therapy with metformin where appropriate.

Claims

1. An aqueous liquid composition comprising the following constituents per 1 ml of the composition:

(a) about 0.025 mg to about 0.1 mg desPro³⁶exendin-4(1-39)-Lys₆-NH2 or a pharmacologically tolerable salt thereof;

(b) about 3.64 mg insulin glargine or a pharmacologically tolerable salt thereof;

(c) about 3.0 mg methionine

(d) water is present in a quantity sufficient for the volume of the composition to total about 1 mL;

(e) about 2.7 mg m-cresol;

(f) about 20.0 mg 85% glycerol; and

(g) about 0.06 mg zinc chloride,

wherein the composition has a pH in the range from 3.5 to 4.5, and wherein the composition comprises no buffer substances.

2. The aqueous liquid composition of claim 1, wherein the composition exhibits chemical integrity after storage for 6 months at a temperature of +25°

C.

3. The aqueous liquid composition of claim 1, wherein the composition exhibits physical integrity after storage for 6 months at a temperature of +25°

C.

4. The aqueous composition of claim 1, wherein the composition is suitable for parenteral an injectable composition.

5. The aqueous liquid composition of claim 1, wherein at least 80% of the composition'"'"'s active ingredients are in a substantially chemically unchanged form after storage for 6 months at a temperature of +25°

C.

6. The aqueous liquid composition of claim 1, wherein at least 80% of the composition'"'"'s active ingredients are in a substantially physically unchanged form after storage for 6 months at a temperature of +25°

C.

7. The aqueous liquid composition of claim 1, wherein the composition has a pH of 4.5.

8. The aqueous liquid composition of claim 1, wherein the composition comprises an oxidized content if about 1% or less after 1 month of storage.

9. The aqueous liquid composition of claim 1, wherein the composition is pharmacologically tolerable.