Stabilized interferon alpha solutions

• US 5,762,923 A
• Filed: 04/04/1996
• Issued: 06/09/1998
• Est. Priority Date: 04/06/1995
• Status: Expired due to Term

• Current Assignee: Hoffmann-La Roche Incorporated (Roche Holding AG)
• Original Assignee: Hoffmann-La Roche Incorporated (Roche Holding AG)
• Inventors: Kumar, Saran Kandakuri, Gross, Gunter, Del Terzo, Sabino
• Primary Examiner(s): Tsang, Cecilia J.
• Assistant Examiner(s): BORIN, MICHAEL L
• Application Number:
  US08/627,563
• Time in Patent Office: 796 Days
• Field of Search: 424/85.7, 424/85.1
• US Class Current: 424/85.7
• CPC Class Codes: A61K 38/212 IFN-alpha
• 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 9/0019 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

Abstract

An aqueous interferon composition which comprises an amount of interferon-alpha dissolved in water with a non-ionic detergent and benzyl alcohol in amounts sufficient to stabilize the amount of interferon-alpha, which composition contains an amount of acidic buffer which provides a pH of 4.5 to 6.0, and may also contain an isotonizing agent.

Claims

1. A human serum albumin-free aqueous interferon composition which comprises about 10⁶ -10⁸ IU/ml of interferon-alpha dissolved in water with a non-ionic detergent and 8 to about 20 mg/ml of benzyl alcohol which composition contains an amount of buffer which provides a pH of 4.5 to 6.0 and is characterized by absence of human serum albumin.

2. An aqueous interferon composition of claim 1 which contains an isotonizing agent in an amount sufficient to provide an isotonic solution.

3. An aqueous interferon composition of claim 1 wherein the pH is from pH 4.9-pH 5.1.

4. An aqueous interferon composition of claim 1 wherein the amount of interferon-alpha is about 10⁶ -10⁸ IU/ml;

the amount of non-ionic detergent is about 0.01-0.5 mg/ml; and

the amount of buffer is about 10-15 mmolar.

5. An aqueous interferon composition of claim 2 wherein the interferon-alpha is interferon-alpha 2a or PEG-interferon alpha 2a;

the non-ionic detergent is polyoxyethylene(20)sorbitan monooleate;

the buffer is selected from ammonium acetate and sodium lactate; and

the isotonizing agent is selected from sodium chloride, mannitol, glycerol, arginine, lysine, histidine, methionine, and ethanolamine in an amount sufficient to provide an isotonic solution.

6. An aqueous interferon composition of claim 5 wherein the amount of interferon-alpha 2a is 1-36×

10⁶ IU/ml;

the amount of polyoxyethylene(20)sorbitan monooleate is 0.2 mg/ml;

the amount of ammonium acetate or sodium lactate is 10 mM, the amount of benzyl alcohol is 10 mg/ml; and

the isotonizing agent is sodium chloride.

7. An aqueous interferon composition of claim 5 wherein the interferon-alpha is PEG-interferon alpha 2a in the amount of 1-36×

10⁶ IU/ml;

the amount of polyoxyethylene(20)sorbitan monooleate is 0.05 mg/ml;

the buffer is 13 mM ammonium acetate;

the amount of benzyl alcohol is 10 mg/ml; and

the isotonizing agent is sodium chloride or mannitol.

8. An aqueous interferon composition of claim 7 wherein the PEG-interferon alpha 2a is in the amount of 1-18×

10⁶ IU/ml.

9. An aqueous interferon composition of claim 2 wherein the interferon-alpha is PEG-interferon alpha 2a in the amount of 1-18×

10⁶ IU/ml;

the amount of benzyl alcohol is 10 mg/ml;

the buffer is 0.462 mg/ml glacial acetic acid and 2.617 mg/ml sodium acetate;

the amount of polyoxyethylene (20) sorbitan monooleate is 0.05 mg/ml; and

the isotonizing agent is sodium chloride.