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Fine Chemicals Seite 1 Oct. 25..2001 G.Richet The Fine Art of Fine Chemicals ® TSEAC REXIM S.A. Amino Acids Production.

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Presentation on theme: "Fine Chemicals Seite 1 Oct. 25..2001 G.Richet The Fine Art of Fine Chemicals ® TSEAC REXIM S.A. Amino Acids Production."— Presentation transcript:

1 Fine Chemicals Seite 1 Oct. 25..2001 G.Richet The Fine Art of Fine Chemicals ® TSEAC REXIM S.A. Amino Acids Production

2 Fine Chemicals Seite 2 Oct. 25..2001 G.Richet The Fine Art of Fine Chemicals ® TSEAC REXIM S.A. Rexim is 100% Degussa since 20 years Headquarter :Courbevoie, France, (Paris) Production Plants for Pharmaceutical Grade L-amino acids : Ham, France Konstanz, Germany Nanning, China (2001) Production Plants for Feed Grade Aminoacids Blair,Mobile, USA (L-lys,DL-met) Antwerp, Belgium (DL-met ) Wesseling, Germany ( DL-met ) Slovakia ( L-lys,L-thr )

3 Fine Chemicals Seite 3 Oct. 25..2001 G.Richet The Fine Art of Fine Chemicals ® TSEAC REXIM S.A. Processes Production Plants for Pharmaceutical Grade L-Amino Acids : Ham, France : Extraction from Proteins hydrolyzates Purification from lower grades ( feed,...) Konstanz, Germany : Enzymatic resolution Nanning, China : Biocatalysis and fermentation Production Plants for Feed Grade Amino acids Synthesis Fermentation

4 Fine Chemicals Seite 4 Oct. 25..2001 G.Richet The Fine Art of Fine Chemicals ® TSEAC REXIM S.A. L-Amino Acids Extraction from Proteins Hydrolysates 1/8 Serine, Threonine, Proline, Hydroxyproline, Alanine, Valine, Isoleucine, Leucine Phenylalanine, Histidine, Arginine ( asp, glu, gly, lys, tyr,met)

5 Fine Chemicals Seite 5 Oct. 25..2001 G.Richet The Fine Art of Fine Chemicals ® TSEAC REXIM S.A. Extraction from Proteins Hydrolysates 2/8 :Process Selection Purification of natural Proteins Acidic Hydrolysis Filtration Ion exchange chromatographic steps Charcoal treatment (Ultrafiltration) Crystallization 1 Charcoal treatment Ultrafiltration Crystallization 2,Drying

6 Fine Chemicals Seite 6 Oct. 25..2001 G.Richet The Fine Art of Fine Chemicals ® TSEAC REXIM S.A. Extraction from Proteins Hydrolysates 3/8 Selection Purification of natural Proteins and pure Chemicals: Keratins from feathers ( chicken,ducks,turkeys ) Gelatin from pigs Bovine free materials Chemicals like NH3, HCl, NaOH, H2SO4,alcohols Regular Suppliers Audits

7 Fine Chemicals Seite 7 Oct. 25..2001 G.Richet The Fine Art of Fine Chemicals ® TSEAC REXIM S.A. Extraction from Proteins Hydrolysates 4/8 Acidic Hydrolysis of Proteins: Conditions choosen for complete disappearance of proteinic materials : only short peptides (2-4 units ) remain. Use of a large excess of concentrated HCl. Keratin is heated 6 hrs at 105°C Gelatin is heated 4 hrs at 120°C

8 Fine Chemicals Seite 8 Oct. 25..2001 G.Richet The Fine Art of Fine Chemicals ® TSEAC REXIM S.A. Extraction from Proteins Hydrolysates 5/8 Ion exchange chromatography : Main step achieving separation of single amino acids. Separation based on ionic properties but also on differences on sizes and hydrophobicities ( peptides separated aswell)

9 Fine Chemicals Seite 9 Oct. 25..2001 G.Richet The Fine Art of Fine Chemicals ® TSEAC REXIM S.A. Extraction from Proteins Hydrolysates 6/8 Activated mineral Charcoal treatment : Purification based on surface adsorption : Charcoal fixes coloured entities and macromolecules ( endotoxines... )

10 Fine Chemicals Seite 10 Oct. 25..2001 G.Richet The Fine Art of Fine Chemicals ® TSEAC REXIM S.A. Extraction from Proteins Hydrolysates 7/8 Ultrafiltration : Main Purpose is biological purification : removal of endotoxines for making infusion grade amino acids. Done on membranes with cut off of 5000 to 10 000 daltons; Efficiency measured by limulus test. Crystallization : A recognized method for purification as demonstrated by HPLC

11 Fine Chemicals Seite 11 Oct. 25..2001 G.Richet The Fine Art of Fine Chemicals ® TSEAC REXIM S.A. Extraction from Proteins Hydrolysates 8/8 Biological Safety TSE Expert reports from Pasteur Institute since 1992 Viral Safety Validation report (Pasteur Institute /1998 ) using : Encephalomyocarditis virus Canine Parvovirus classified as « resistant » and « highly resistant » by the CPMP (Committee for Proprietary Medicinal Products )

12 Fine Chemicals Seite 12 Oct. 25..2001 G.Richet The Fine Art of Fine Chemicals ® TSEAC REXIM S.A. Purification from lower Grade ( feed ) Typical examples : asp,glu, gly,lys Process uses activated charcoal,ultrafiltration and Recrystallization Origins: asp : bioconversion of fumaric acid glu, lys : fermentation gly : synthesis

13 Fine Chemicals Seite 13 Oct. 25..2001 G.Richet The Fine Art of Fine Chemicals ® TSEAC REXIM S.A. Enzymatic resolution at Konstanz L- Methionine 1. DL- Methionine -> N-acetyl-DL-Methionine 2. acylase -> L-met + N-acetyl-D-Met 3. ion exchange separation -> L- Methionine -> N-acetyl-D-Met 4. -> N-acetyl-DL-Methionine

14 Fine Chemicals Seite 14 Oct. 25..2001 G.Richet The Fine Art of Fine Chemicals ® TSEAC REXIM S.A. Biocatalysis in China Fumaric acid + NH 3 + fumarase  L-aspartic acid Bioreaction, filtration, precipitation, filtration, drying L-aspartic + aspartate  decarboxylase L-alanine Bioreaction, filtration, precipitation, filtration, drying

15 Fine Chemicals Seite 15 Oct. 25..2001 G.Richet The Fine Art of Fine Chemicals ® TSEAC REXIM S.A. Fermentation in China Sugar + Cornsteep + NH 3  L- Valine Biomass removal, ion exchange,crystallisation,filtration, drying Sugar + Cornsteep + NH 3  L- Isoleucine Biomass removal, ion exchange,crystallisation,filtration, drying

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