182
Development of both enzyme fermentation and starch conversion technology
was started simultaneously around the mid of the 1970s, in the microbial and processing laboratories of Chinoin, respectively. The researcher had to tackle (i) selecting the microorganism producing cyclodextrin glucosyltransferase enzyme; (ii)
building up analytical methods for cyclodextrin glucosyltransferase enzyme activity; (iii) optimizing the conditions for cultivation; (iv) separating the enzyme from
culture medium; (v) purification and characterization of the enzyme; (vi) selection
of starch and optimization of hydrolysis by alpha-amylase; (vii) optimizing the
enzymatic conversion of starch to the mixture of cyclic and acyclic maltodextrins;
(viii) optimizing the conditions for the desired ratio of alpha-cyclodextrin, betacyclodextrin, and gamma-cyclodextrin in the conversion mixture; (ix) developing
an alpha-cyclodextrin-specific conversion pathway; (x) developing a gammacyclodextrin- specific conversion pathway; (xi) developing analytical techniques for
characterization of the composition of the conversion mixture; (xii) separating
cyclodextrin(s), purification, and crystallization; (xiii) scaling up the production;
and (xiv) developing an immobilized enzyme.
As a result of substantial development, the first 100 kg beta-cyclodextrin was
produced in 1978. Parallel to the development of the cyclodextrin production, the
technologies for the preparation of some cyclodextrin derivatives were also scaled
up: hydroxypropyl-beta-cyclodextrin as a parenteral drug carrier and cyclodextrin
bead polymer for wound healing were selected for industrial production.
This chapter gives the details on how the development of the production technologies proceeded and how the difficulties were overcome until the final technologies were documented and the industrial production realized.
Keywords History · Production · Enzyme production · Native cyclodextrins ·
Cyclodextrin derivatives · Cyclodextrin polymer · Industry
4.1 Introduction
Cyclodextrin research in Chinoin Pharmaceutical and Chemical Works Co. Ltd.,
one of the biggest pharmaceutical companies in Hungary and Central Europe,
started after Professor József Szejtli established the Biochemical Research
Laboratory in 1972. The radical development of cyclodextrin processing began after
1975 and continued in close collaboration with the Biotechnology Development
Department of the factory. The first cyclodextrin-related research paper on achievements of laboratory was published in 1975. Also in this and subsequent years, the
authors of this chapter were involved in the cyclodextrin research to witness or
participate in research and development of cyclodextrin production.
In the mid of the 1970s, it was generally accepted that (i) cyclodextrins were
interesting compounds able to molecularly encapsulate various organic materials;
(ii) cyclodextrins were toxic, hindering practical utilization; and (iii) cyclodextrin
production was complicated and expensive; therefore large-scale applications were
É. Fenyvesi et al.
Development of both enzyme fermentation and starch conversion technology
was started simultaneously around the mid of the 1970s, in the microbial and processing laboratories of Chinoin, respectively. The researcher had to tackle (i) selecting the microorganism producing cyclodextrin glucosyltransferase enzyme; (ii)
building up analytical methods for cyclodextrin glucosyltransferase enzyme activity; (iii) optimizing the conditions for cultivation; (iv) separating the enzyme from
culture medium; (v) purification and characterization of the enzyme; (vi) selection
of starch and optimization of hydrolysis by alpha-amylase; (vii) optimizing the
enzymatic conversion of starch to the mixture of cyclic and acyclic maltodextrins;
(viii) optimizing the conditions for the desired ratio of alpha-cyclodextrin, betacyclodextrin, and gamma-cyclodextrin in the conversion mixture; (ix) developing
an alpha-cyclodextrin-specific conversion pathway; (x) developing a gammacyclodextrin- specific conversion pathway; (xi) developing analytical techniques for
characterization of the composition of the conversion mixture; (xii) separating
cyclodextrin(s), purification, and crystallization; (xiii) scaling up the production;
and (xiv) developing an immobilized enzyme.
As a result of substantial development, the first 100 kg beta-cyclodextrin was
produced in 1978. Parallel to the development of the cyclodextrin production, the
technologies for the preparation of some cyclodextrin derivatives were also scaled
up: hydroxypropyl-beta-cyclodextrin as a parenteral drug carrier and cyclodextrin
bead polymer for wound healing were selected for industrial production.
This chapter gives the details on how the development of the production technologies proceeded and how the difficulties were overcome until the final technologies were documented and the industrial production realized.
Keywords History · Production · Enzyme production · Native cyclodextrins ·
Cyclodextrin derivatives · Cyclodextrin polymer · Industry
4.1 Introduction
Cyclodextrin research in Chinoin Pharmaceutical and Chemical Works Co. Ltd.,
one of the biggest pharmaceutical companies in Hungary and Central Europe,
started after Professor József Szejtli established the Biochemical Research
Laboratory in 1972. The radical development of cyclodextrin processing began after
1975 and continued in close collaboration with the Biotechnology Development
Department of the factory. The first cyclodextrin-related research paper on achievements of laboratory was published in 1975. Also in this and subsequent years, the
authors of this chapter were involved in the cyclodextrin research to witness or
participate in research and development of cyclodextrin production.
In the mid of the 1970s, it was generally accepted that (i) cyclodextrins were
interesting compounds able to molecularly encapsulate various organic materials;
(ii) cyclodextrins were toxic, hindering practical utilization; and (iii) cyclodextrin
production was complicated and expensive; therefore large-scale applications were
É. Fenyvesi et al.