Lyophilized Preparation of Botulinum Toxin

Abstract

There are provided a lyophilized preparation of botulinum toxin without a protein stabilizer derived from animals. The lyophilized preparation of botulinum toxin according to the present invention can maintain an activity of botulinum toxin, and also exhibit excellent long-term storage stability even under conditions of high temperature, which may occur when botulinum toxin is stored, delivered, and processed.

What is claimed is: 
     
         1 . A pharmaceutical lyophilized preparation comprising:
 botulinum toxin, polysorbate, and methionine; and   one or more components selected from the group consisting of sugar, sugar alcohol, and an ionic compound,   wherein the preparation is free of albumin, and   wherein stability of the botulinum toxin is maintained for at least 30 days at room temperature.   
     
     
         2 . The pharmaceutical lyophilized preparation of  claim 1 , wherein the botulinum toxin is selected from the group consisting of botulinum serotypes A, B, C, D, E, F, and G. 
     
     
         3 . The pharmaceutical lyophilized preparation of  claim 1 , wherein the botulinum toxin is selected from the group consisting of a form without a complexing protein and a form with a complexing protein. 
     
     
         4 . The pharmaceutical lyophilized preparation of  claim 1 , wherein the polysorbate is any one of polysorbates 20, 40, 60, 80, and 100. 
     
     
         5 . The pharmaceutical lyophilized preparation of  claim 1 , wherein the polysorbate is included in an amount of 0.01 to 2 mg with respect to 100 units of the botulinum toxin. 
     
     
         6 . The pharmaceutical lyophilized preparation of  claim 1 , wherein the methionine is included in an amount of 0.01 to 10 mg with respect to 100 units of the botulinum toxin. 
     
     
         7 . The pharmaceutical lyophilized preparation of  claim 1 , wherein the sugar is one or more selected from the group consisting of trehalose, sucrose, maltose, fructose, raffinose, lactose, and glucose. 
     
     
         8 . The pharmaceutical lyophilized preparation of  claim 1 , wherein the sugar is included in an amount of 0.1 to 50 mg with respect to 100 units of the botulinum toxin. 
     
     
         9 . The pharmaceutical lyophilized preparation of  claim 1 , wherein the sugar alcohol is one or more selected from the group consisting of cyclodextrin, mannitol, sorbitol, glycerol, xylitol, and inositol. 
     
     
         10 . The pharmaceutical lyophilized preparation of  claim 1 , wherein the sugar alcohol is included in an amount of 0.1 to 50 mg with respect to 100 units of the botulinum toxin. 
     
     
         11 . The pharmaceutical lyophilized preparation of  claim 1 , wherein the ionic compound is one or more selected from the group consisting of sodium chloride, sodium phosphate, ammonium phosphate, magnesium sulfate, sodium acetate, sodium lactate, sodium succinate, sodium propionate, and potassium phosphate. 
     
     
         12 . The pharmaceutical lyophilized preparation of  claim 1 , wherein the ionic compound is included in an amount of 0.1 to 10 mg with respect to 100 units of the botulinum toxin. 
     
     
         13 . A pharmaceutical lyophilized preparation comprising:
 botulinum toxin, polysorbate, methionine, sugar, and an ionic compound,   wherein the preparation is free of albumin, and   wherein stability of the botulinum toxin is maintained for at least 30 days at room temperature.   
     
     
         14 . A pharmaceutical lyophilized preparation comprising:
 botulinum toxin, polysorbate 20, methionine, sucrose, and sodium chloride,   wherein the preparation is free of albumin, and   wherein stability of the botulinum toxin is maintained for at least 30 days at room temperature.