Stabilized erythropoietin preparations

• US 4,992,419 A
• Filed: 09/01/1988
• Issued: 02/12/1991
• Est. Priority Date: 09/05/1987
• Status: Expired due to Term

• Current Assignee: Boehringer Mannheim GmbH (Roche Holding AG)
• Original Assignee: Boehringer Mannheim GmbH (Roche Holding AG)
• Inventors: Demmer, Frtiz, Gruber, Werner, Woog, Heinrich, Markl, Hans-Jorg
• Primary Examiner(s): NOT, DEFINED
• Application Number:
  US07/240,005
• Time in Patent Office: 894 Days
• Field of Search: 514/21, 514/8, 514/12, 514/970-971
• US Class Current: 514/7.7
• 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 31/17 having the group >N—C(O)—N< or >N—C(S)—N<, e.g. urea, thiourea, carmustine isoureas, isothioureas A61K31/155; sulfonylureas A61K31/64
• CPC Class Codes: A61K 31/195 having an amino group
• CPC Class Codes: A61K 33/14 Alkali metal chlorides; Alkaline earth metal chlorides
• CPC Class Codes: A61K 38/1709 from mammals
• CPC Class Codes: A61K 38/1816 Erythropoietin [EPO]
• CPC Class Codes: A61K 47/18 Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
• CPC Class Codes: A61K 47/183 Amino acids, e.g. glycine, EDTA or aspartame
• 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

A compatible, storage-stable human protein preparation containing a human protein, a physiologically compatible buffer and optionally complex formers, isotonia-adjusting agents, calcium chloride and other materials usual for injection purposes which, in an injectable form, contains 5 to 50 g./liter urea, 1 to 50 g./liter amino acid and 0.05 to 5 g./liter non-ionic wetting agent. A process for the production of this preparation is also disclosed.

Claims

1. Compatible, storage-stable erythropoietin preparation comprising erythropoietin, a physiologically compatible buffer, 5 to 50 g/liter urea and 1 to 50 g/liter amino acids.

3. An erythropoietin preparation according to claim 1 or 2 further comprising a complex former or an isotonia-adjusting agent.

4. An erythropoietin preparation according to claim 1 or 2 wherein the amino acid is selected from the group consisting of glycine, L-alanine, L-arginine, L-leucine, L-isoleucine, L-2-phenylalanine, L-glutamic acid, L-threonine and mixtures thereof.

6. An erythropoietin preparation according to claim 3 which comprises calcium chloride as a complex former.

7. An erythropoietin preparation according to claim 3 which comprises sodium chloride as an isotonia-adjusting adjuvent.

8. An erythropoietin preparation according to claim 1 or 2 wherein said phosphate buffer is selected from the group consisting of sodium dihydrogen phosphate, disodium hydrogen phosphate and a mixture thereof.

9. An erythropoietin preparation according to claim 1 or 2 which is in lyophilisized form.

10. An erythropoietin preparation according to claim 3 which is in lyophilisized form.

11. An erythropoietin preparation according to claim 1 or 2 which is in aqueous liquid form.

12. An erythropoietin preparation according to claim 11 which contains, per injection dosage unit of 1 to 5 ml, from 100 to 1 million U of erythropoietin.

13. An erythropoietin preparation according to claim 12 which contains, per injection dosage unit of 1 to 5 ml, from 100 to 20,000 U of erythropoietin.

14. An erythropoietin preparation according to claim 3 which is in aqueous liquid form.

15. An erythropoietin preparation according to claim 14 which contains, per injection dosage unit of 1 to 5 ml, from 100 to 1 million U of erythropoietin.

2. Compatible, storage-stable erythropoietin preparation comprising erythropoietin, a physiologically compatible buffer, 5 to 50 g/liter urea, 1 to 50 g/liter amino acid and 0.05 to 5 g/liter non-ionic wetting agent.

5. An erythropoietin preparation according to claim 2 in which the wetting agent is polyethylene sorbitan laurate.

16. An erythropoietin preparation according to claim 5 which contains, per injection dosage unit of 1 to 5 ml, from 100 to 1 million U of erythropoietin.