Process for producing cell culture media

Abstract

The present invention relates to a process for manufacturing dry powder cell culture media. The preparation and usage of mixed particles generated by co-lyophilisation leads to cell culture media with improved solubility without changing the chemical composition.

1 . A method for improving the solubility of a dry powder cell culture medium by
 a) identifying the one or more poorly soluble components in the said cell culture medium   b) co-lyophilizing the components identified in step a) with at least one other component of said cell culture medium as a carrier component   c) preparing the said dry powder cell culture medium by mixing the one or more co-lyophilisates generated in step b) with the other components of the cell culture medium and optionally milling the resulting mixture   
     
     
         2 . Method according to  claim 1  characterized in that the one or more poorly soluble components are compounds with a solubility in water at 25° C. of less than 10 g/l. 
     
     
         3 . Method according to  claim 1 , characterized in that the one or more poorly soluble components are selected from the group of cystine, iron(Ill)citrate hydrate, iron(Ill)chloride hexahydrate and/or tyrosine. 
     
     
         4 . Method according to  claim 1 , characterized in that the one or more carrier components are selected from the following group:
 Calcium Chloride, anhydrous and hydrated forms   Di-Potassium hydrogen phosphate, anhydrous and hydrated forms   Di-Sodium hydrogen phosphat, anhydrous and hydrated forms   Magnesium chloride, anhydrous and hydrated forms   Magnesium sulfate, anhydrous and hydrated forms   Potassium chloride   Potassium dihydrogen phosphate   Sodium Chloride   Sodium dihydrogen phosphate, anhydrous and hydrate forms   Sodium hydrogen carbonate   D(−)-Fructose   D(−)-Mannitol   D(+)-Galactose   D(+)-Glucose, anhydrous and hydrate forms   D(+)-Mannose   Glycine   Glycyl-L-tyrosine Hydrate   L-alanine   L-Alanyl-L-Glutamine   L-Arginine and hydxrochloride forms   L-Asparagine monohydrate   L-Aspartic Acid   L-Cysteine and Hydrochloride/Hydrate forms   L-Glutamic acid   L-Glutamine   L-Histidine and hydrochloride forms   L-Hydroxyproline   L-Isoleucine   L-Leucine   L-Lysine Monohydrate and hydrochloride forms   L-Methionine   L-Phenylalanine   L-Proline   L-Serine   L-Threonine   L-Tryptophan   L-Valine   Mono-sodium-L-aspartate-monohydrate   Phospho-Tyrosine Di-Sodium Salt   Sodium L-glutamate monohydrate   HEPES_CCM   HEPES Sodium   MOPS   Choline Chloride   Poloxamer 188   Sodium acetate trihydrate   myo-Inositol   Oxalacetic acid   Succinic Acid   Pyruvic Acid Sodium Salt   alpha-Ketoglutaric Acid Disodiumsalt Dihydrate   beta-Glycerophosphoric acid disodium salt pentahydrate or mixtures thereof   
     
     
         5 . Method according to  claim 1 , characterized in that the one or more carrier components are selected from the group of sodium chloride, D(−)-fructose, D(−)-mannitol, D(+)-galactose, D(+)-mannose, glucose anhydrate as well as hydrated form of glucose, glycine, L-alanine, L-arginine and its hydrochloride forms, L-asparagine monohydrate, L-aspartic acid, L-cysteine and hydrochloride/hydrate forms, L-glutamic acid, L-glutamine, L-histidine and hydrochloride forms, L-isoleucine, L-leucine, L-lysine monohydrate and hydrochloride forms, L-methionine, L-phenylalanine, L-proline, L-serine, L-threonine, L-tryptophan, L-valine, mono-sodium-L-aspartate-monohydrate, sodium glutamate monohydrate, HEPES and sodium forms, MOPS, choline chloride, poloxamers, or mixtures thereof. 
     
     
         6 . Method according to  claim 1 , characterized in that in the co-lyophilisate the amount of the poorly soluble component is between 1 and 50% (w/w) of the amount of the carrier component. 
     
     
         7 . Method according to  claim 1 , characterized in that in step b) the co-lyophilisation is performed by generating an aqueous solution of the components, freezing the mixture and removing the liquid under reduced pressure. 
     
     
         8 . A process for manufacturing cell culture media by
 a) co-lyophilizing one or more components of said cell culture medium which are poorly soluble with one or more other components of the cell culture medium   b) mixing the one or more co-lyophilisates generated in step a) with the other components of the cell culture medium   c) optionally subjecting the mixture of step b) to milling   
     
     
         9 . A process according to  claim 8 , characterized in that the one or more poorly soluble components are compounds which have a solubility in water at 25° C. of less than 10 g/l. 
     
     
         10 . A process according to  claim 8 , characterized in that the one or more poorly soluble components are selected from the group of cystine, iron(III)citrate hydrate, iron(III)chloride hexahydrate and/or tyrosine. 
     
     
         11 . A process according to  claim 8 , characterized in that the
 one or more carrier components are selected from the group of sodium chloride, D(−)-fructose, D(−)-mannitol, D(+)-galactose, D(+)-mannose, glucose anhydrate as well as hydrated form of glucose, glycine, L-alanine, L-arginine and its hydrochloride forms, L-asparagine monohydrate, L-aspartic acid, L-cysteine and hydrochloride/hydrate forms, L-glutamic acid, L-glutamine, L-histidine and hydrochloride forms, L-isoleucine, L-leucine, L-lysine monohydrate and hydrochloride forms, L-methionine, L-phenylalanine, L-proline, L-serine, L-threonine, L-tryptophan, L-valine, mono-sodium-L-aspartate-monohydrate, sodium glutamate monohydrate, HEPES and sodium forms, MOPS, choline chloride, poloxamers, or mixtures thereof.   
     
     
         12 . A process according to  claim 8 , characterized in that in the co-lyophilisate the amount of the poorly soluble component is between 1 and 50% (w/w) of the amount of the carrier component. 
     
     
         13 . A process according to  claim 8 , characterized in that in step a) the co-lyophilisation is performed by generating an aqueous solution of the components, freezing the mixture and removing the liquid under reduced pressure.