US4835105A
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US
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Process for the preparation of high-purity gamma- and alpha-cyclodextrins
Assignee: Chinoin Private Co Ltd
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Filing: 1987-07-09
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Granted: 1989-05-30
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Expires: 2007-07-09
Abstract
Abstract The invention relates to a process for the preparation of high-purity gamma- and alpha-cyclodextrin starting from a starch substrate of low reducing capacity, partially hydrolysed with alpha-amylase. According to the invention a starch substrate of low reducing capacity partially hydrolysed with alpha-amylase is converted with cyclodextrin glucosyl transferase, after the addition of an aliphatic ketone of the formula R 1 COR 2 , in which R 1 and R 2 stand for a straight or branched chained alkyl group having from 1 to 6 carbon atoms, and/or a phenol derivative of the formula R 3 R 4 PheOH, wherein R 3 and R 4 are hydrogen, alkyl having from 1 to 4 carbon atoms, or R 3 and R 4 together form phenyl group, Phe stand for phenyl group, OH is hydroxyl and/or a benzene derivative of the formula R 5 R 6 Phe, wherein R 5 and R 6 are hydrogen, alkyl having from 1 to 4 carbon atoms, or R 5 and R 6 together form phenyl group, Phe is phenyl, as a precipitating agent, and if desired, alpha- and/or gamma-cyclodextrin is isolated from the conversion mixture in a crude form, or after further purification, in a pure form.
Inventors
- 👤 Gabor Seres
- 👤 Miklos Jarai
- 👤 Sandor Piukovich
- 👤 Maria Szigetvari nee Gabanyi
- 👤 Jozsef Szejtli
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-03 05:08
CPC Classifications
C; C08; C08B; C08B37/00; C08B37/0006; C08B37/0009; C08B37/0012
Claims Analysis
Total Claims: 12
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.
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USPTO Annuity & Maintenance Windows
| 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 |