Growth hormone crystals and a process for production of these GH-crystals

Abstract

A process for producing cation crystals of growth hormone or growth hormone derivatives, as well as growth hormone and growth derivatives. The process of producing the growth hormone crystals includes the steps of (a) adding cations of inorganic or organic nature and an organic solvent or a mixture of inorganic solvents as a pH between 5.0 and 6.8 to a solution of growth hormone or derivatives. (b) growing growth hormone crystals at a temperature from about 0 to 30° C. and (c) isolating the cation crystals.

1 . A process for production of cation crystals of growth hormone (GH) or of GH derivatives, comprising the following steps: 
 a) to a solution of GH or derivatives thereof is added cations of inorganic or organic nature and an organic solvent or a mixture of organic solvents at a pH between 5.0 and 6.8,    b) growing of crystals at a temperature from about 0 to about 30° C., and    c) isolation of the cation crystals by known means.    
   
   
       2 . A process according to  claim 1 , wherein the pH in step a) is from 5.8 to 6.5.  
   
   
       3 . A process according to  claim 1 , wherein the organic solvent is selected from the group consisting of short chained aliphatic, cyclic or aromatic alcohols or ketones.  
   
   
       4 . A process according to  claim 3 , wherein the organic solvent is selected from the group consisting of acetone, methanol, ethanol and 2-propanol.  
   
   
       5 . A process according to  claim 4 , wherein the organic solvent is ethanol or acetone.  
   
   
       6 . A process according to any of  claims 1  to  5  wherein the organic solvent is added in a concentration of about 0.1 to about 50% v/v.  
   
   
       7 . A process according to  claim 6 , wherein the organic solvent is added in a concentration of 0.1 to 30% preferably from 0.1 to 20%, more preferred from 5 to 1% and most preferred from 6 to 12%.  
   
   
       8 . A process according to  claim 1 , wherein the cation is a divalent cation.  
   
   
       9 . A process according to  claim 8 , wherein the divalent cation is Zn ++.    
   
   
       10 . A process according to  claim 9 , wherein Zn ++  is added in a concentration below the limit for unspecific precipitation of amorphous material.  
   
   
       11 . A process according to  claim 10 , wherein Zn ++  is added in a concentration from 0.5 to 10 mol Zn ++  /mol GH.  
   
   
       12 . A process according to  claim 11  wherein the concentration of Zn ++  is from 1.0 to 3.0 mol Zn ++ /mol GH.  
   
   
       13 . A process according to  claim 1 , wherein the growth hormone is hGH or derivatives thereof.  
   
   
       14 . A process according to  claim 1 , wherein the temperature in step b) is from about 4 to about 25° C.  
   
   
       15 . Cation crystals of human growth hormone (hGH) or hGH derivatives.  
   
   
       16 . Crystals according to  claim 15 , wherein the cation is Zn ++.    
   
   
       17 . Crystals according to  claim 16 , wherein the molar ratio between Zn ++  and GH is from about 0.2 to about 10.  
   
   
       18 . Pharmaceutical preparations, characterized in that they contain crystals according to  claim 15 .  
   
   
       19 . (canceled)