213
4.2.6 The End of the Story
After the political changes in Hungary, Chinoin was sold to Sanofi Aventis in 1991.
The new owner was not interested in bioprocesses. So, the fermentation plant was
closed, and with this also the enzyme production was finished (Sipos et al. 1996). At
that time, the site of cyclodextrin production was at Győr Distillery Co. Ltd. in
western Hungary. The management has foreseen difficulties in selling cyclodextrins
without the support of a big pharmaceutical company. Therefore, the cyclodextrin
production was stopped soon after changing ownership in Chinoin. Although
Hungary was one of the first industrial cyclodextrin producers in the world, the high
potential of cyclodextrin market (today thousands of tons in a year) was not predicted. At that time, two European cyclodextrin manufacturers have already been on
the market: Roquette Frères in France and Wacker Chemie in Germany.
With finishing the cyclodextrin production, the hydroxypropyl-beta-cyclodextrin
manufacturing was also given up. Nowadays, both Roquette Frères and Wacker
Chemie produce this derivative in extremely high volume. Experimental production
of bead polymers was also stopped after the technology transfer to Wacker Chemie
(Germany), and they are not produced any more.
Only the cyclodextrin research survived in Hungary by establishing a spin-off
company by Professor Szejtli and his co-workers in the Biochemical Research
Laboratory in 1989. CycloLab, a small private research company, not only has
maintained its leading position in cyclodextrin research, but it has also developed an
independent process for the production of sulfobutyl ether beta-cyclodextrin, an
alternative parenteral drug carrier, and since 2008 it has been an FDA-approved
GMP manufacturer of this excipient with multiple ton annual production
(CycloLab 2019).
4.3 Conclusions
This chapter tells how the cyclodextrin production was started in Hungary in the
1970s and 1980s of the twentieth century, at about the same time as in Japan. The
difficulties experienced in finding and isolating the proper enzyme, separating the
individual cyclodextrins from the conversion mixture, analyzing the products, and
scaling up to hundred kilograms scale were gradually overcome till the production
of several tons beta-cyclodextrin started. The methods for producing alphacyclodextrin and gamma-cyclodextrin were also worked out, and some experimental lots obtained. Similarly, the productions of hydroxypropyl-beta-cyclodextrin and
beta-cyclodextrin bead polymer were ready to be industrialized when the productions were abandoned owing to political changes. The laboratory headed by
Professor Szejtli became a knowledge center of cyclodextrin research and development. After about two decades of break in cyclodextrin production in Hungary, this
4 History of Cyclodextrin Production in Hungary
4.2.6 The End of the Story
After the political changes in Hungary, Chinoin was sold to Sanofi Aventis in 1991.
The new owner was not interested in bioprocesses. So, the fermentation plant was
closed, and with this also the enzyme production was finished (Sipos et al. 1996). At
that time, the site of cyclodextrin production was at Győr Distillery Co. Ltd. in
western Hungary. The management has foreseen difficulties in selling cyclodextrins
without the support of a big pharmaceutical company. Therefore, the cyclodextrin
production was stopped soon after changing ownership in Chinoin. Although
Hungary was one of the first industrial cyclodextrin producers in the world, the high
potential of cyclodextrin market (today thousands of tons in a year) was not predicted. At that time, two European cyclodextrin manufacturers have already been on
the market: Roquette Frères in France and Wacker Chemie in Germany.
With finishing the cyclodextrin production, the hydroxypropyl-beta-cyclodextrin
manufacturing was also given up. Nowadays, both Roquette Frères and Wacker
Chemie produce this derivative in extremely high volume. Experimental production
of bead polymers was also stopped after the technology transfer to Wacker Chemie
(Germany), and they are not produced any more.
Only the cyclodextrin research survived in Hungary by establishing a spin-off
company by Professor Szejtli and his co-workers in the Biochemical Research
Laboratory in 1989. CycloLab, a small private research company, not only has
maintained its leading position in cyclodextrin research, but it has also developed an
independent process for the production of sulfobutyl ether beta-cyclodextrin, an
alternative parenteral drug carrier, and since 2008 it has been an FDA-approved
GMP manufacturer of this excipient with multiple ton annual production
(CycloLab 2019).
4.3 Conclusions
This chapter tells how the cyclodextrin production was started in Hungary in the
1970s and 1980s of the twentieth century, at about the same time as in Japan. The
difficulties experienced in finding and isolating the proper enzyme, separating the
individual cyclodextrins from the conversion mixture, analyzing the products, and
scaling up to hundred kilograms scale were gradually overcome till the production
of several tons beta-cyclodextrin started. The methods for producing alphacyclodextrin and gamma-cyclodextrin were also worked out, and some experimental lots obtained. Similarly, the productions of hydroxypropyl-beta-cyclodextrin and
beta-cyclodextrin bead polymer were ready to be industrialized when the productions were abandoned owing to political changes. The laboratory headed by
Professor Szejtli became a knowledge center of cyclodextrin research and development. After about two decades of break in cyclodextrin production in Hungary, this
4 History of Cyclodextrin Production in Hungary