Acidic Insulin Preparations Having Improved Stability

• US 20100216692A1
• Filed: 05/04/2010
• Published: 08/26/2010
• Est. Priority Date: 06/18/2002
• Status: Abandoned Application

• Current Assignee: Sanofi-Aventis Deutschland GmbH (Sanofi )
• Original Assignee: Sanofi-Aventis Deutschland GmbH (Sanofi )
• Inventors: BRUNNER-SCHWARZ, Anette, LILL, Norbert
• Application Number:
  US12/773,356
• Publication Number:
  US 20100216692A1
• Time in Patent Office: Days
• US Class Current: 514/5.900
• 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 31/7032 attached to a polyol, i.e. compounds having two or more free or esterified hydroxy groups, including the hydroxy group involved in the glycosidic linkage, e.g. monoglucosyldiacylglycerides, lactobionic acid, gangliosides
• CPC Class Codes: A61K 38/28 Insulins
• 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 9/0019 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 3/06 Antihyperlipidemics
• 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 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Abstract

The invention relates to a pharmaceutical formulation comprising a polypeptide selected from the group consisting of insulin, an insulin metabolite, an insulin analog, an insulin derivative and combinations thereof; a surfactant or combinations of two or more surfactants; optionally a preservative or combinations of two or more preservatives; and optionally an isotonicizing agent, buffers or further excipients or combinations thereof, the pharmaceutical formulation having a pH in the acidic range.

Claims

1. A pharmaceutical formulation comprising:

(a) Gly(A21), Arg(B31), Arg(B32)-human insulin;

(b) polysorbate 20;

(c) sodium chloride;

(d) glycerol;

(e) m-cresol; and

(f) water,

wherein the pharmaceutical formulation has a pH in the acidic range from 3.5 to 6.8.

2. The pharmaceutical formulation as claimed in claim 1, wherein the Gly(A21), Arg(B31), Arg(B32)-human insulin is present at a concentration of about 1.4 to about 35 mg per milliliter.

3. The pharmaceutical formulation as claimed in claim 1, wherein the Gly(A21), Arg(B31), Arg(B32)-human insulin is present at a concentration of about 3.6 mg per milliliter.

4. The pharmaceutical formulation as claimed in claim 3, further including zinc.

5. The pharmaceutical formulation as claimed in claim 1, wherein polysorbate 20 is present at a concentration of about 5 to 120 μ

g per milliliter.

6. The pharmaceutical formulation as claimed in claim 1, wherein polysorbate 20 is present at a concentration of about 20 to 75 μ

g per milliliter.

7. The pharmaceutical formulation as claimed in claim 1, wherein sodium chloride is present at a concentration of up to 150 mM.

8. The pharmaceutical formulation as claimed in claim 1, wherein glycerol is present at a concentration of about 100 to 250 mM.

9. The pharmaceutical formulation as claimed in claim 1, further comprising a buffer.

10. The pharmaceutical formulation as claimed in claim 9, wherein the buffer is chosen from TRIS, phosphate, citrate, acetate, and glycylglycine.

11. The pharmaceutical formulation as claimed in claim 10, wherein said buffer is present in a concentration of 5-250 mM.

12. The pharmaceutical formulation as claimed in claimed 1, wherein the pharmaceutical formulation has a pH in the acidic range from 3.5 to 4.5.

13. The pharmaceutical formulation as claimed in claimed 1, wherein the pharmaceutical formulation has a pH of 4 (+/−

0.2).