29
production and the details of the mechanism. These two researchers also laid down
the basis of the enzymology of dextrins, and their findings were validated and used
for over 30 years. Myrbäck and Gjorling (1945) and Cori and Cori (1946) also confirmed that the enzyme which catalyzed the degradation of starch into dextrins was
mainly produced by bacillus strains. These two groups were the first to describe the
action mechanism involved in the enzyme synthesis of Schardinger dextrins and to
point out that the rate of hydrolysis of dextrins was much slower in its initial phase
than later on. In addition, the authors noted that, after a few days, the Schardinger
dextrins formed under the action of Bacillus macerans gradually disappeared. This
was also observed by Kneen and Beckord (1946), by French (French et al. 1948),
and later by Hale and Rawlins (1951). The explanation was given by French which
introduced the reversibility of the action of the enzyme (French et al. 1948). In
1948, French’s group proposed a mechanism of action based on a transglucosylation reaction to interpret the formation of dextrins by Bacillus macerans (French
et al. 1948). Their results demonstrated that Bacillus macerans was capable of producing a glycosidic exchange reaction between maltose and cyclohexaamylose
which resulted in the formation of higher weight saccharides, confirming the concept of glycosidic exchange introduced by Cori and Cori (1946). French pointed out
that the enzyme performed three transglucosylation reactions involving cyclization,
coupling, and disproportionation, as well as a hydrolysis reaction. This mechanism
proposed by French and detailed in his comprehensive review (French 1957a) was
only demonstrated in the 2000s (Lee and Robyt 2001; Qi et al. 2004). In 1950,
Akiya and co-workers also proposed a mechanism of action and claimed the “discovery” of a new strain of Bacillus macerans (Akiya and Watanabe 1950a, b, c),
although Hudson’s group have previously shown that all examined strains of
Bacillus macerans were capable of forming Schardinger dextrins (Tilden and
Hudson 1939, 1942; Tilden et al. 1942).
1.3.7 The First Schardinger Dextrin-Related Patents
The first patent on Schardinger dextrins was registered in 1925 by the German Fritz
Lange for IG Farbenindustrie (Fig. 1.13). This patent entitled Verfahren zur gewinnung von polyamylosen focused on the isolation of polyamyloses (Lange 1925).
Freudenberg, Cramer, and Plieninger filed the first industrial cyclodextrin-related
patent in 1953, called “Method for preparation of inclusion compounds of physiologically active organic compound” (Freudenberg et al. 1953). The patent described
the most important aspects of the applications of cyclodextrins in drug formulations
(Fig. 1.14). The authors detailed specific effects that could be achieved by complexation of drugs with cyclodextrin complexation such as enhancement of solubility of
poorly soluble drugs, protection of easily oxidizable substances against atmospheric
oxidation, reduction of the loss of highly volatile substances, etc. In 1987, Cramer
wrote: “At that time, I saw the first possibilities for a technology transfer and I took
a patent. This, unfortunately, never found any industrial application” (Cramer 1987).
1 History of Cyclodextrins
production and the details of the mechanism. These two researchers also laid down
the basis of the enzymology of dextrins, and their findings were validated and used
for over 30 years. Myrbäck and Gjorling (1945) and Cori and Cori (1946) also confirmed that the enzyme which catalyzed the degradation of starch into dextrins was
mainly produced by bacillus strains. These two groups were the first to describe the
action mechanism involved in the enzyme synthesis of Schardinger dextrins and to
point out that the rate of hydrolysis of dextrins was much slower in its initial phase
than later on. In addition, the authors noted that, after a few days, the Schardinger
dextrins formed under the action of Bacillus macerans gradually disappeared. This
was also observed by Kneen and Beckord (1946), by French (French et al. 1948),
and later by Hale and Rawlins (1951). The explanation was given by French which
introduced the reversibility of the action of the enzyme (French et al. 1948). In
1948, French’s group proposed a mechanism of action based on a transglucosylation reaction to interpret the formation of dextrins by Bacillus macerans (French
et al. 1948). Their results demonstrated that Bacillus macerans was capable of producing a glycosidic exchange reaction between maltose and cyclohexaamylose
which resulted in the formation of higher weight saccharides, confirming the concept of glycosidic exchange introduced by Cori and Cori (1946). French pointed out
that the enzyme performed three transglucosylation reactions involving cyclization,
coupling, and disproportionation, as well as a hydrolysis reaction. This mechanism
proposed by French and detailed in his comprehensive review (French 1957a) was
only demonstrated in the 2000s (Lee and Robyt 2001; Qi et al. 2004). In 1950,
Akiya and co-workers also proposed a mechanism of action and claimed the “discovery” of a new strain of Bacillus macerans (Akiya and Watanabe 1950a, b, c),
although Hudson’s group have previously shown that all examined strains of
Bacillus macerans were capable of forming Schardinger dextrins (Tilden and
Hudson 1939, 1942; Tilden et al. 1942).
1.3.7 The First Schardinger Dextrin-Related Patents
The first patent on Schardinger dextrins was registered in 1925 by the German Fritz
Lange for IG Farbenindustrie (Fig. 1.13). This patent entitled Verfahren zur gewinnung von polyamylosen focused on the isolation of polyamyloses (Lange 1925).
Freudenberg, Cramer, and Plieninger filed the first industrial cyclodextrin-related
patent in 1953, called “Method for preparation of inclusion compounds of physiologically active organic compound” (Freudenberg et al. 1953). The patent described
the most important aspects of the applications of cyclodextrins in drug formulations
(Fig. 1.14). The authors detailed specific effects that could be achieved by complexation of drugs with cyclodextrin complexation such as enhancement of solubility of
poorly soluble drugs, protection of easily oxidizable substances against atmospheric
oxidation, reduction of the loss of highly volatile substances, etc. In 1987, Cramer
wrote: “At that time, I saw the first possibilities for a technology transfer and I took
a patent. This, unfortunately, never found any industrial application” (Cramer 1987).
1 History of Cyclodextrins