US4835105A — Process for the preparation of high-purity gamma-…

Claim 1

Independent Claim 196 words

A process for the preparation of a cyclodextrin mixture comprising beta-cyclodextrin and gamma-cyclodextrin, each in the form of a ternary complex, which comprises the steps of: (a) partially hydrolyzing starch with alpha-amylase of bacillus origin in the presence of calcium ions at a pH of 7 at 80° C. until the reducing capacity of the hydrolysate becomes less than 8 D.E.; (b) interrupting the enzymatic hydrolysis carried out in step (a) by inactivating the alpha-amylase by heating to 120° C., under an overpressure of 1 bar; (c) treating the partially hydrolyzed starch with cyclodextrin glucosyl transferase of bacillus origin, having an activity of about 24 to 50 kitahata units/g; (d) adding to the hydrolysate at 35 to 45° C. in an amount of about 10% by volume a precipitating mixture of equal proportions of methyl ethyl ketone and a phenolic compound selected from the group consisting of 1-naphthol and 2,4-dimethylphenol; and (e) allowing the hydrolysate and the precipitating mixture to react for a period of 1 to 3 days to facilitate consecutive formation of alpha-cyclodextrin, which then forms beta-cyclodextrin and gamma-cyclodextrin, the latter as an insoluble ternary complex and the former as a soluble ternary complex.

Claim 2

Dependent Claim 196 words

A process for the preparation of a cyclodextrin mixture comprising beta-cyclodextrin and gamma-cyclodextrin, each in the form of a ternary complex, which comprises the steps of: (a) partially hydrolyzing starch with alpha-amylase of bacillus origin in the presence of calcium ions at a pH of 7 at 80° C. until the reducing capacity of the hydrolysate becomes less than 8 D.E.; (b) interrupting the enzymatic hydrolysis carried out in step (a) by inactivating the alpha-amylase by heating to 120° C., under an overpressure of 1 bar; (c) treating the partially hydrolyzed starch with cyclodextrin glucosyl transferase of bacillus origin, having an activity of about 24 to 50 kitahata units/g; (d) adding to the hydrolysate at 35 to 45° C. in an amount of about 10% by volume a precipitating mixture of equal proportions of methyl ethyl ketone and a phenolic compound selected from the group consisting of 1-naphthol and 2,4-dimethylphenol; and (e) allowing the hydrolysate and the precipitating mixture to react for a period of 1 to 3 days to facilitate consecutive formation of alpha-cyclodextrin, which then forms beta-cyclodextrin and gamma-cyclodextrin, the latter as an insoluble ternary complex and the former as a soluble ternary complex.

Claim 3

Dependent Claim 65 words

The process for the preparation of a cyclodextrin mixture defined in claim 1 which further comprises the following steps: (f) filtering the cyclodextrin mixture formed in step (e) to separate and recover a precipitate containing gamma-cyclodextrin ternary complex and a filtrate containing beta-cyclodextrin ternary complex; and (g) allowing the filtrate to stand for 2 days at 40° C. to precipitate the ternary complex containing beta-cyclodextrin.

Claim 4

Dependent Claim 68 words

The process for the preparation of a cyclodextrin mixture defined in claim 2 which further comprises the step of extracting the precipitate formed in step (f) with a lower alkanol to eliminate the precipitating agent and then selectively extracting gamma-cyclodextrin from the precipitate by extraction with a 50 to 70% aqueous solution of a lower alkanol, and purifying the extract by adsorption and ion exchange, and crystallizing gamma-cyclodextrin.

Claim 5

Dependent Claim 171 words

A process for the preparation of a cyclodextrin mixture comprising beta-cyclodextrin as the principal product in the form of a ternary complex, which comprises the steps of: (a) partially hydrolyzing starch with alpha-amylase of bacillus origin in the presence of calcium ions at a pH of 7 at 80° C. until the reducing capacity of the hydrolysate is less than 8 D.E.; (b) interrupting the enzymatic hydrolysis carried out in step (a by inactivating the alpha-amylase by heating to 120° C. under an overpressure of 1 bar; (c) treating the hydrolysate with cyclodextrin glucosyl transferase of bacillus origin having an activity of about 24 to 50 kitahata units/g; (d) adding to the hydrolysate at 35 to 45° C. in an amount of about 10% by volume a precipitating mixture of equal proportions of methyl ethyl ketone and toluene; and (e) allowing the hydrolysate and the precipitating mixture to react for a period of 1 to 3 days to facilitate consecutive formation of alpha-cyclodextrin, which then forms beta-cyclodextrin as a ternary complex.

Claim 6

Dependent Claim 171 words

A process for the preparation of a cyclodextrin mixture comprising beta-cyclodextrin as the principal product in the form of a ternary complex, which comprises the steps of: (a) partially hydrolyzing starch with alpha-amylase of bacillus origin in the presence of calcium ions at a pH of 7 at 80° C. until the reducing capacity of the hydrolysate is less than 8 D.E.; (b) interrupting the enzymatic hydrolysis carried out in step (a by inactivating the alpha-amylase by heating to 120° C. under an overpressure of 1 bar; (c) treating the hydrolysate with cyclodextrin glucosyl transferase of bacillus origin having an activity of about 24 to 50 kitahata units/g; (d) adding to the hydrolysate at 35 to 45° C. in an amount of about 10% by volume a precipitating mixture of equal proportions of methyl ethyl ketone and toluene; and (e) allowing the hydrolysate and the precipitating mixture to react for a period of 1 to 3 days to facilitate consecutive formation of alpha-cyclodextrin, which then forms beta-cyclodextrin as a ternary complex.

Claim 7

Dependent Claim 218 words

A process for the preparation of a cyclodextrin mixture comprising beta-cyclodextrin and gamma-cyclodextrin, each in the form of a ternary complex, which comprises the steps of: (a) partially hydrolyzing starch with alpha-almylase of bacillus origin in the presence of calcium ions at a pH of 7 to 80° C. until the reducing capacity of the hydrolysate becomes less than 8 D.E.; (b) interrupting the enzymatic hydrolysis carried out in step (a) by inactivating the alpha-amylase by heating to 120° C., under an overpressure of 1 bar; (c) treating the partially hydrolyzed starch with cyclodextrin glucosyl transferase of bacillus origin, having an activity of about 24 to 50 kitahata units/g; (d) adding to the hydrolysate at 35 to 45° C. in an amount of about 10% by volume a precipitating mixture of equal proportions of a ketone of the Formula: ##STR1## wherein R 1 and R 2 are each individually C 1 to C 6 straight or branched chain alkyl and an aromatic compound selected from the group consisting of 2,4-dimethylphenol, 2,6-dimethylphenol, 1-naphthol, 2-naphthol, and naphthalene; and (e) allowing the hydrolysate and the precipitating mixture to react for a period of 1 to 3 days to facilitate consecutive formation of alpha-cyclodextrin, beta-cyclodextrin, and gamma-cyclodextrin, the latter as an insoluble ternary complex and the former as a soluble ternary complex.

Claim 8

Dependent Claim 218 words

A process for the preparation of a cyclodextrin mixture comprising beta-cyclodextrin and gamma-cyclodextrin, each in the form of a ternary complex, which comprises the steps of: (a) partially hydrolyzing starch with alpha-almylase of bacillus origin in the presence of calcium ions at a pH of 7 to 80° C. until the reducing capacity of the hydrolysate becomes less than 8 D.E.; (b) interrupting the enzymatic hydrolysis carried out in step (a) by inactivating the alpha-amylase by heating to 120° C., under an overpressure of 1 bar; (c) treating the partially hydrolyzed starch with cyclodextrin glucosyl transferase of bacillus origin, having an activity of about 24 to 50 kitahata units/g; (d) adding to the hydrolysate at 35 to 45° C. in an amount of about 10% by volume a precipitating mixture of equal proportions of a ketone of the Formula: ##STR1## wherein R 1 and R 2 are each individually C 1 to C 6 straight or branched chain alkyl and an aromatic compound selected from the group consisting of 2,4-dimethylphenol, 2,6-dimethylphenol, 1-naphthol, 2-naphthol, and naphthalene; and (e) allowing the hydrolysate and the precipitating mixture to react for a period of 1 to 3 days to facilitate consecutive formation of alpha-cyclodextrin, beta-cyclodextrin, and gamma-cyclodextrin, the latter as an insoluble ternary complex and the former as a soluble ternary complex.

Claim 9

Dependent Claim 65 words

The process for the preparation of a cyclodextrin mixtue defined in claim 5 which further comprises the following steps: (f) filtering the cyclodextrin mixture formed in step (e) to separate and recover a precipitate containing gamma-cyclodextrin ternary complex and a filtrate containing beta-cyclodextrin ternary complex; and (g) allowing the filtrate to stand for 2 days at 40° C. to precipitate the ternary complex containing beta-cyclodextrin.

Claim 10

Dependent Claim 68 words

The process for the preparation of a cyclodextrin mixture defined in claim 6 which further comprises the step of extracting the precipitate formed in step (f) with a lower alkanol to eliminate the precipitating agent and then selectively extracting gamma-cyclodextrin from the precipitate by extraction with a 50 to 70% aqueous solution of a lower alkanol, and purifying the extract by adsorption and ion exchange, and crystallizing gamma-cyclodextrin.

Claim 11

Dependent Claim 216 words

A process for the preparation of a cyclodextrin mixture comprising beta-cyclodextrin as the principal product in the form of a ternary complex, which comprises the steps of: (a) partially hydrolyzing starch with alpha-amylase of bacillus origin in the presence of calcium ions at a pH of 7 at 80° C. until the reducing capacity of the hydrolysate is less than 8 D.E.; (b) interrupting the enzymatic hydrolysis carried out in step (a) by inactivating the alpha-amylase by heating to 120° C. under an overpressure of 1 bar; (c) treating the hydrolysate with cyclodextrin glucosyl transferase of bacillus origin having an activity of about 24 to 50 kitahata units/g; (d) adding to the hydrolysate at 35 to 45° C. in an amount of about 10% by volume a precipitating mixture of equal proportions of a ketone of the formula: ##STR2## wherein R 1 and R 2 are each individually C 1 to C 6 straight or branched chain alkyl, and an aromatic hydrocarbon of the formula: ##STR3## wherein R 5 and R 6 are each individually hydrogen or C 1 to C 4 alkyl; and (e) allowing the hydrolysate and the precipitating mixture to react for a period of 1 to 3 days to facilitate consecutive formation of alpha-cyclodextrin, which then forms beta-cyclodextrin as a ternary complex.

Claim 12

Dependent Claim 216 words

A process for the preparation of a cyclodextrin mixture comprising beta-cyclodextrin as the principal product in the form of a ternary complex, which comprises the steps of: (a) partially hydrolyzing starch with alpha-amylase of bacillus origin in the presence of calcium ions at a pH of 7 at 80° C. until the reducing capacity of the hydrolysate is less than 8 D.E.; (b) interrupting the enzymatic hydrolysis carried out in step (a) by inactivating the alpha-amylase by heating to 120° C. under an overpressure of 1 bar; (c) treating the hydrolysate with cyclodextrin glucosyl transferase of bacillus origin having an activity of about 24 to 50 kitahata units/g; (d) adding to the hydrolysate at 35 to 45° C. in an amount of about 10% by volume a precipitating mixture of equal proportions of a ketone of the formula: ##STR2## wherein R 1 and R 2 are each individually C 1 to C 6 straight or branched chain alkyl, and an aromatic hydrocarbon of the formula: ##STR3## wherein R 5 and R 6 are each individually hydrogen or C 1 to C 4 alkyl; and (e) allowing the hydrolysate and the precipitating mixture to react for a period of 1 to 3 days to facilitate consecutive formation of alpha-cyclodextrin, which then forms beta-cyclodextrin as a ternary complex.

Annuity Stage	Window Opens	Payment Deadline	Surcharge Period Until	Estimated Fee	Status
3.5 Years (Year 4)	1992-05-29	1992-11-28	1993-05-30	$2000.00	Window Closed / Lapsed
7.5 Years (Year 8)	1996-05-29	1996-11-28	1997-05-30	$3760.00	Window Closed / Lapsed
11.5 Years (Year 12)	2000-05-29	2000-11-28	2001-05-30	$7700.00	Window Closed / Lapsed

Process for the preparation of high-purity gamma- and alpha-cyclodextrins

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