Method for making precipitated particles
AssigneeUniversity of Strathclyde
InventorsJan Vos, Andrew John MacLeod, Barry Douglas Moore
Life of this patent
Estimating the term…
Abstract
The present invention relates to the provision of a novel method for preparing dry amorphous precipitated protein particles. In particular to a method provides amorphous precipitated protein particles suitable for use in dry protein formulations which can be reconstituted to provide clear, foam free concentrated protein solutions.
Claims21
A method for the preparation of dry amorphous precipitated particles that comprise protein, sucrose, arginine and glutamic acid or lactobionic acid comprising:
- (i) preparation of an aqueous solution for precipitation comprising:
- (a) a protein at a mass concentration of greater than about 50 mg/ml;
- (b) sucrose at a mass concentration between about 30% to about 95% of the mass concentration of the protein;
- (c) arginine at a molar concentration of less than about 50 mM;
- (d) glutamic acid or lactobionic acid at a molar concentration of less than about 50 mM;
- and
- (e) optionally a surfactant;
- (ii) combining said aqueous solution for precipitation with at least a 12 fold volume of one or more protic organic solvents at a temperature in the range of from about 15° C. to about 50° C. to produce a miscible solvent mixture and suspension of amorphous precipitated particles which each comprise protein, sucrose, arginine and glutamic acid or lactobionic acid;
- (iii) concentrating said suspension and/or removing the remaining solvent to isolate the dry amorphous precipitated particles comprising said protein;
- and wherein said particles can be reconstituted to form an aqueous solution suitable for subcutaneous administration of the protein at a concentration of greater than 140 mg/ml protein.
-21. (canceled)
A method for the preparation of dry amorphous precipitated protein formulations suitable for reconstitution into highly concentrated protein solutions comprising:
- (i) preparation of an aqueous solution for precipitation comprising:
- a) a protein at a mass concentration of greater than about 50 mg/ml;
- b) an excipient of molecular mass of greater than about 170 Da at a mass concentration of from about 40% to about 95% relative to that of said protein;
- c) a buffer;
- d) a cationic precipitation stabilizing additive at a molar concentration of less than about 50 mM and/or an anionic precipitation stabilizing additive at a molar concentration of less than about 50 mM;
- e) optionally additional surfactants, additional buffers or salts,
- (ii) combining or mixing said aqueous solution with a greater than 12 fold or larger volume of a protic organic solvent at a temperature in the range of from about 15° C. to about 50° C., to coprecipitate the solid components of the aqueous solution, resulting in formation of a suspension of amorphous protein containing particles, and isolating the amorphous precipitated protein containing particles from said suspension in the form of a dry powder.
Dependencies are inferred from the claim text.