Pharmaceutical compositions containing hedgehog protein

• US 6,207,718 B1
• Filed: 08/02/1999
• Issued: 03/27/2001
• Est. Priority Date: 08/07/1998
• Status: Expired due to Fees

• Current Assignee: Curis, Inc.
• Original Assignee: Ontogeny, Inc. (Curis, Inc.)
• Inventors: Papadimitriou, Apollon
• Primary Examiner(s): FUBARA, BLESSING M
• Application Number:
  US09/365,948
• Time in Patent Office: 603 Days
• Field of Search: 514/772.3, 424/422, 424/461, 424/484, 424/486
• US Class Current: 514/772.3
• CPC Class Codes: A61K 38/1703 from vertebrates
• CPC Class Codes: A61K 47/02 Inorganic compounds
• 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 47/36 Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
• CPC Class Codes: A61K 47/40 Cyclodextrins; Derivatives thereof
• 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 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 25/02 for peripheral neuropathies
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

A composition of a hedgehog protein which includes as an additive cyclodextrin, a non-ionic detergent, an anionic saccharide and/or ionic salt containing zinc ions, magnesium ions, calcium ions and/or sulfate ions is especially stable at room temperature.

Claims

1. A composition adapted for formulating unit dosage forms for administration to a patient wherein said composition comprises an aqueous solution containing a hedgehog protein;

and an additive being present in an effective amount to stabilize said hedgehog protein in the aqueous solution, wherein said additive is selected from the group consisting of ionic salts, cyclodextrin, non-ionic detergent, anionic saccharide and mixtures thereof, said ionic salt containing an ion selected from the group consisting of zinc, sulfur, magnesium, calcium, arginine, argininium and mixtures thereof.

2. The composition according to claim 1, wherein said hedgehog protein is present in the composition in an amount from about 0.1 mg/ml to about 100 mg/ml.

3. The composition according to claim 1 or 2, wherein said hedgehog protein is palmitoylated.

4. The composition according to claim 1, wherein the additive is an anionic saccharide selected from the group consisting of chondroitin sulfate and heparin.

5. The composition according to claim 1, wherein the additive is polyoxysorbate.

6. The composition according to claim 1, wherein the additive is cyclodextrin sulfate.

7. The composition according to claim 1, wherein the additive is argininium sulfate.

8. The composition according to claim 1, wherein the composition contains a molar excess of the additive relative to the amount of the hedgehog protein.

9. The composition according to claim 8, wherein the additive is present in an amount of from about 1 to about 1000 fold greater than the amount of hedgehog protein.

10. The composition according to claim 9, wherein the additive is present in an amount of from about 1 to about 100 fold greater than the amount of the hedgehog protein.

11. The composition according to claim 1, wherein the additive is an ionic salt, said ionic salt being present in the composition at a concentration of from about 0.01 mmol/l to about 500 mmol/l.

12. The composition according to claim 1, wherein the additive is cyclodextrin, said cyclodextrin being present in the composition at a concentration of from about 1% to about 20% by weight of said composition.

13. The composition according to claim 1, wherein the additive is a non-ionic detergent, said non-ionic detergent being present in the composition at a concentration of from about 0.01% to about 0.1% of said composition.

14. The composition according to claim 1, wherein the additive is an ionic salt containing arginine or an argininium ion, said arginine or argininium ion being present in the composition at a concentration of about 10 mmol/l to about 700 mmol/l.

15. The composition according to claim 1, wherein the hedgehog protein is bound to a biocompatible carrier.

16. The composition according to claim 1, wherein the biocompatible carrier is hydrophilic.

17. The composition according to claim 15, wherein the hydrophilic carrier is a polymer.

18. The composition according to claim 1, wherein the composition is buffered in a range of from about pH 3 to about pH 10.

19. The composition according to claim 1, wherein the composition is lyophilized.