5
The period between 1950 and 1970, known as the period of maturation of
notions, focused on inclusion complexes with Cramer’s work in the foreground. At
the beginning of the 1950s, French finally demonstrated the chemical cyclic structures of cycloamyloses. In 1953, Cramer gave the basis for supramolecular catalysis
involving cyclodextrins, and the same year, with Freudenberg and Plieninger, he
published the first patent concerning the applications of cyclodextrins in pharmaceutical formulations. In 1956, Cramer introduced and detailed the notion of an
inclusion complex. From that time on, the interest in cyclodextrins increased. During
the maturation period, the works of Casu on the conformation and spectroscopic
characterization of cyclodextrins were acknowledged to have brought an important
contribution. At the same time, much attention was also focused on their use for
catalysis and as enzyme models, and one name stands out in particular in the enzymology and catalysis by cyclodextrins: Bender (Crini 2014). Nonetheless, until the
mid-1970s, the three main native cyclodextrins, i.e., α-, β-, and γ-cyclodextrins,
available only in small quantities, were long considered as just laboratory curiosities (Thoma and Stewart 1965; Caesar 1968; Kainuma 1984; Clarke et al. 1988). In
the way of industrial development, the three main obstacles were their price, e.g., in
1975 1 kg of β-cyclodextrin had a price of about 1500 $ (Szejtli 1982a), their presumed toxicity (French 1957a), and the lack of sufficient knowledge of these substances (Szejtli 1982a). In addition, very few researchers were convinced of the
industrial potential of cyclodextrins.
The 1970s were marked by two important events: firstly, several manufacturers
started to produce and to commercialize cyclodextrins; at that time, due to improvements in the production of cyclodextrins, their prices have dropped significantly.
Secondly, the first toxicological studies had established that β-cyclodextrin administrated orally was a harmless substance. As a result, this has led to spectacular
progress. From then on, the period of use began and cyclodextrins found many
industrial applications. During this period of utilization, four names stand out:
Saenger, Szejtli, Nagai, and Pitha. In the mid-1970s, pharmaceutical and food applications started to appear and rapidly gained ground, especially in Japan (Hamada
et al. 1975; Szejtli 1977; Pitha et al. 1983; Uekama and Otagiri 1987; Frömming
and Szejtli 1994). In 1980, Saenger published the first comprehensive review about
the potential industrial applications of cyclodextrins (Saenger 1980). The first
International Cyclodextrin Symposium organized by Szejtli took place in Budapest
in 1981, and 1 year later, he wrote the first comprehensive cyclodextrin book (Szejtli
1982a). At that time, many interesting catalysts based on cyclodextrins were also
constructed for biomimetic chemistry and other processes of interest such as artificial enzymes (Breslow 1979; Breslow and Dong 1998). Both from an academic and
industrial point of view, the number of communications then started to increase
exponentially, as did the filing of patents.
In the mid-1980s, cyclodextrins were produced in large quantities and commercialized at a reasonable price, i.e., 10–15 $/kg (Szejtli 1982a). Other industrial
applications have become possible. In 1984, the first chromatographic columns
were marketed (Armstrong 1984; Ward and Armstrong 1986, 1988; Armstrong and
Jin 1989). Since then, an increasing interest in cyclodextrins and their possible
1 History of Cyclodextrins
The period between 1950 and 1970, known as the period of maturation of
notions, focused on inclusion complexes with Cramer’s work in the foreground. At
the beginning of the 1950s, French finally demonstrated the chemical cyclic structures of cycloamyloses. In 1953, Cramer gave the basis for supramolecular catalysis
involving cyclodextrins, and the same year, with Freudenberg and Plieninger, he
published the first patent concerning the applications of cyclodextrins in pharmaceutical formulations. In 1956, Cramer introduced and detailed the notion of an
inclusion complex. From that time on, the interest in cyclodextrins increased. During
the maturation period, the works of Casu on the conformation and spectroscopic
characterization of cyclodextrins were acknowledged to have brought an important
contribution. At the same time, much attention was also focused on their use for
catalysis and as enzyme models, and one name stands out in particular in the enzymology and catalysis by cyclodextrins: Bender (Crini 2014). Nonetheless, until the
mid-1970s, the three main native cyclodextrins, i.e., α-, β-, and γ-cyclodextrins,
available only in small quantities, were long considered as just laboratory curiosities (Thoma and Stewart 1965; Caesar 1968; Kainuma 1984; Clarke et al. 1988). In
the way of industrial development, the three main obstacles were their price, e.g., in
1975 1 kg of β-cyclodextrin had a price of about 1500 $ (Szejtli 1982a), their presumed toxicity (French 1957a), and the lack of sufficient knowledge of these substances (Szejtli 1982a). In addition, very few researchers were convinced of the
industrial potential of cyclodextrins.
The 1970s were marked by two important events: firstly, several manufacturers
started to produce and to commercialize cyclodextrins; at that time, due to improvements in the production of cyclodextrins, their prices have dropped significantly.
Secondly, the first toxicological studies had established that β-cyclodextrin administrated orally was a harmless substance. As a result, this has led to spectacular
progress. From then on, the period of use began and cyclodextrins found many
industrial applications. During this period of utilization, four names stand out:
Saenger, Szejtli, Nagai, and Pitha. In the mid-1970s, pharmaceutical and food applications started to appear and rapidly gained ground, especially in Japan (Hamada
et al. 1975; Szejtli 1977; Pitha et al. 1983; Uekama and Otagiri 1987; Frömming
and Szejtli 1994). In 1980, Saenger published the first comprehensive review about
the potential industrial applications of cyclodextrins (Saenger 1980). The first
International Cyclodextrin Symposium organized by Szejtli took place in Budapest
in 1981, and 1 year later, he wrote the first comprehensive cyclodextrin book (Szejtli
1982a). At that time, many interesting catalysts based on cyclodextrins were also
constructed for biomimetic chemistry and other processes of interest such as artificial enzymes (Breslow 1979; Breslow and Dong 1998). Both from an academic and
industrial point of view, the number of communications then started to increase
exponentially, as did the filing of patents.
In the mid-1980s, cyclodextrins were produced in large quantities and commercialized at a reasonable price, i.e., 10–15 $/kg (Szejtli 1982a). Other industrial
applications have become possible. In 1984, the first chromatographic columns
were marketed (Armstrong 1984; Ward and Armstrong 1986, 1988; Armstrong and
Jin 1989). Since then, an increasing interest in cyclodextrins and their possible
1 History of Cyclodextrins