Method of formulating IGF-I with growth hormone

• US 5,597,802 A
• Filed: 06/02/1995
• Issued: 01/28/1997
• Est. Priority Date: 06/07/1990
• Status: Expired due to Term

• Current Assignee: Genentech, Inc. (Roche Holding AG)
• Original Assignee: Genentech, Inc. (Roche Holding AG)
• Inventors: Clark, Ross G., Oeswein, James Q., Yeung, Douglas A.
• Primary Examiner(s): SCHAIN, HOWARD
• Application Number:
  US08/458,595
• Time in Patent Office: 606 Days
• Field of Search: 514/12, 514/3, 514/4, 514/21
• US Class Current: 514/4.8
• 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 38/27 Growth hormone [GH], i.e. somatotropin
• CPC Class Codes: A61K 38/30 Insulin-like growth factors, i.e. somatomedins, e.g. IGF-1, IGF-2 insulin-like growth factor binding protein A61K38/1754
• 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
• CPC Class Codes: C07K 14/4702 Regulators; Modulating activity
• CPC Class Codes: G01N 33/6872 Intracellular protein regulatory factors and their receptors, e.g. including ion channels

Abstract

A formulation for IGF-I is disclosed that is useful in treating hyperglycemic disorders and, in combination with growth hormone, in enhancing growth of a mammal. Also disclosed is a process for preparing a formulation of growth hormone and IGF-I from the IGF-I formulation. The IGF-I formulation comprises about 2-20 mg/ml of IGF-I, about 2-50 mg/ml of an osmolyte, about 1-15 mg/ml of a stabilizer, and a buffered solution at about pH 5-5.5, optionally with a surfactant.

Claims

1. A process for preparing a formulation comprising mixing an IGF-I-containing composition comprising about 2-20 mg/ml of IGF-I, about 2-50 mg/ml of an osmolyte, about 1-15 mg/ml of a stabilizer, and a buffered solution at about pH. 5-5.5 with a buffered solution comprising growth hormone at pH about 6 in a dose (mg) ratio of from about 2:

1 to 100;

1 IGF-I;

growth hormone up to a dose no greater than about 5 mg/ml of growth hormone.

2. The process of claim 1 wherein the osmolyte in the IGF-I-containing composition is sodium chloride or mannitol and the stabilizer is benzyl alcohol or phenol or both.

3. The process of claim 2 wherein the buffered solution of growth hormone comprises about 1 to 10 mg/ml growth hormone in about 5 to 15 mg/ml of an inorganic salt, about 1-5 mg/ml of a stabilizer, about 1-5 mg/ml of a surfactant, and sodium citrate buffer at about pH 6.

4. The process of claim 3 wherein the buffered solution of growth hormone comprises about 3-5 mg/ml growth hormone, about 8-9 mg/ml of sodium chloride, about 1-3 mg/ml of phenol, about 1-3 mg/ml of polysorbate 20, and about 10 mM sodium citrate, about pH 6.

5. The process of claim 1 further comprising storing the final formulation at a temperature of about 2°

-8°

C. for up to about two weeks.

6. The process of claim 1, further comprising lyophilizing the final formulation.

7. The process of claim 6 further comprising reconstituting the lyophilized formulation with water.