Growth-promoting composition and its use

• US 5,374,620 A
• Filed: 06/04/1993
• Issued: 12/20/1994
• 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: Cronin, Michael J., Clark, Ross G., Oeswein, James Q., Yeung, Douglas A.
• Primary Examiner(s): Moezie, F. T.
• Application Number:
  US08/071,818
• Time in Patent Office: 564 Days
• Field of Search: 514/3, 514/4, 514/12, 514/21, 530/399, 930/10, 930/120
• 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: Y10S 930/12 Growth hormone, growth factor other than t-cell or b-cell growth factor, and growth hormone releasing factor; related peptides

Abstract

A combined formulation for IGF-I and growth hormone (GH) is useful for enhancing growth of a mammal. This formulation, which may be administered by infusion or injection to enhance growth, comprises IGF-I and GH, each in amounts of 0.1 to 100 mg/ml, in a pharmaceutically acceptable carrier at a pH of about 5-6 containing a surfactant, wherein the amounts of IGF-I and GH in the composition are effective to promote growth of a mammal more than an equivalent dose of IGF-I or GH alone, and wherein the weight ratio of IGF-I to GH in the composition ranges from 0.002:1 to 240:1.

Claims

1. A growth-promoting composition comprising IGF-I and growth hormone, each in an amount of 0.1 to 100 mg/ml, in a pharmaceutically acceptable carrier at a pH of about 6 containing a surfactant, wherein the amounts of IGF-I and growth hormone in the composition are effective to promote growth of a mammal more than an equivalent dose of IGF-I or growth hormone alone, and wherein the weight ratio of IGF-I to growth hormone in the composition ranges from 0.002:

1 to 240;

1.

2. The composition of claim 1 wherein the amounts of IGF-I and growth hormone in the composition are about 1 to 10 mg/ml each and the weight ratio of IGF-I to growth hormone in the composition ranges from 0.048:

1 to 30;

1.

3. The composition of claim 1 wherein the carrier is an acetic acid salt buffer comprising a sodium counterion.

4. The composition of claim 3 wherein the surfactant is a polysorbate or poloxamer.

5. The composition of claim 4 further comprising a stabilizer.

6. A method for enhancing growth of a mammal comprising administering to the mammal by injection an effective amount of the composition of claim 1 so as to enhance the growth of the mammal over the enhancement in growth achieved using an equivalent dose of IGF-I or GH alone.

7. A method for enhancing growth of a mammal comprising administering to the mammal by infusion an effective amount of the composition of claim 1 so as to enhance the growth of the mammal over the enhancement in growth achieved using an equivalent dose of IGF-I or GH alone.

8. A composition comprising IGF-I and growth hormone in a weight ratio of IGF-I:

growth hormone of between about 2;

1 and 100;

1 (w/w), about 0.05-0.3of an osmolyte, about 0.1-10 mg/ml of a stabilizer, about 1-5 mg/ml of a surfactant, and about 5-100 mM of a buffer at about pH 5-6.

9. The composition of claim 8 wherein the osmolyte is an inorganic salt and the surfactant is nonionic.

10. The composition of claim 9 wherein the inorganic salt sodium chloride or potassium chloride, the stabilizer is phenol or benzyl alcohol, the surfactant is polysorbate or poloxamer, the buffer is sodium acetate or sodium citrate or both, and the amounts of IGF-I and growth hormone are about 2-20 mg/ml and about 0.2-10 mg/ml, respectively, with the weight ratio of IGF-I:

growth hormone being between about 2;

1 and 50;

1.

11. The composition of claim 10 wherein the amount of IGF- I is about 7-10 mg/ml, the amount of growth hormone is about 0.2-1.5 mg/ml, the weight ratio of IGF-I:

growth hormone is about 3;

1 to 20;

1, the amount of sodium chloride is about 5-7 mg/ml, the amount of phenol is about 0.1-3 mg/ml or the amount of benzyl alcohol is about 6-10 mg/ml, the surfactant is polysorbate in an amount of about 1-3 mg/ml, the amount of sodium acetate is about 2.5-4 mg/ml, and the amount of sodium citrate is about 0.1-1 mg/ml.

12. The composition of claim 8 that is lyophilized.

13. A method for enhancing growth of a mammal comprising administering to the mammal by injection an effective amount of the composition of claim 8 so as to enhance the growth of the mammal over the enhancement in growth achieved using an equivalent dose of IGF-I or GH alone.

14. A method for enhancing growth of a mammal comprising administering to theμ

l by infusion an effective amount of the composition of claim 8 so as to enhance the growth of the mammal over the enhancement in growth achieved using an equivalent dose of IGF-I or GH alone.

16. A method for enhancing growth of a mammal comprising administering Go the mammal by injection an effective amount of the composition of claim 8, wherein the weight ratio of IGF-I:

growth hormone administered is between about 2;

1 and 100;

1.

15. A composition comprising IGF-I and growth hormone in a weight ratio of IGF-I:

growth hormone of between about 2;

1 and 100;

1 (w/w), about 0.05-0.3 mM of an inorganic salt, about 0.1-10 mg/ml of a stabilizer, about 1-5mg/ml of a nonionic surfactant, and about 5-100 mM of a buffer at about pH