CN104151451B - A kind of preparation method of hydroxypropyl-beta-cyclodextrin - Google Patents
A kind of preparation method of hydroxypropyl-beta-cyclodextrin Download PDFInfo
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Abstract
The invention discloses a kind of preparation method of hydroxypropyl-beta-cyclodextrin, its step comprises: (1) prepares beta-cyclodextrin product; (2) be that 20% ~ 25% aqueous sodium hydroxide solution is heated to 50-55 DEG C by mass concentration, slowly add the beta-cyclodextrin that step (1) obtains while stirring, continue to stir until beta-cyclodextrin dissolves completely, cool to room temperature, evenly 1 is dripped in 3h-3.5h while stirring under water-bath, 2-propylene oxide 30-35ml, temperature controls at 22 ~ 24 DEG C by dropping process, dropwises rear continuation and stirs 3-5 hour; Wherein the mol ratio of sodium hydroxide, beta-cyclodextrin and 1,2 epoxy prapane is 4:2-3:1-2; (3) the reactant hydrochloric acid that step (2) obtains is neutralized, regulate and make its pH=7; (4) underpressure distillation is carried out to the reaction solution that step (3) obtains, the soup compound dissolve with ethanol obtained, stir, filter, then carry out underpressure distillation and obtain underflow; (5) step (4) gained underflow imported in spray-drier, temperature controls, at 5 ~ 10 DEG C, to obtain white amorphous powder hydroxypropyl-beta-cyclodextrin.It is low that obtained product has substitution value, the advantage that productive rate is high.
Description
Technical field
The present invention relates to a kind of preparation method of medically pharmaceutical excipient, especially relate to a kind of preparation method of hydroxypropyl-beta-cyclodextrin.
Background technology
Cyclodextrin (cyclodextrin, CD), also referred to as ring poly-dextrose, is by the general name of one group of oligose of some D-glucopyranose units circular permutation.Villiers in 1891 by having found cyclodextrin with enzymatic degradation of starch.1904, Schardinger did comparatively detailed description to the preparation of cyclodextrin first.Because this describes, early literatures is also called Schardinger dextrin cyclodextrin.
Cyclodextrin Chemistry obtains the development of advancing by leaps and bounds in two, 30 years in the past.Up to the present, the structure of cyclodextrin and inclusion compound thereof, character and application are summarized, described more than the patents of more than 1400 and thousands of articles to existing many monographs and some treatises.As the simple organic macromolecule of one, cyclodextrin has and scope all kinds of object extremely widely, and such as organic molecule, mineral ion, title complex even rare gas element, forms host-gust inclusion complexes by molecular interaction.Cyclodextrin and derivative thereof are the important research objects of main-guest chemistry, the inclusion compound that cyclodextrin as main body is formed with the transition metal complex effect as object, also referred to as outer coordination sphere compound (secondspherecoordinationcompound).The preparation of cyclodextrin inclusion compound, structure, character and applied research are important contents of Cyclodextrin Chemistry, in addition, about the modification of cyclodextrin, polymerization and Multiple recognition research are also in the ascendant.This respect work can not only provide weak interaction and molecule assembling main body in research supramolecule field, CD derivative after simultaneously modifying or CD polymkeric substance also as good catalyzer and enzyme model, and can be widely used in the various fields such as biomimetic chemistry, catalysis and organic synthesis.In addition, cyclodextrin, in the solubilising of medicine, spices and seasonings, modification and point subpack, illustrates wide application prospect to common people.
Beta-cyclodextrin (β-cyclodextrin, β-CD) be the one of cyclodextrin, it is the cyclic oligosaccharide be formed by connecting by α-(1,4) glycosidic link by the structure of 7 β-Glucopyranoses, its structure is the cylinder shape of hollow wide at the top and narrow at the bottom, the guest inclusion of a certain size and shape can be formed inclusion compound, therefore become the novel inclusion material of noticeable one.Because beta-cyclodextrin solubleness is low, easy crystallization, separation, purification, nontoxicity, readily biodegradable, and production cost is lower, be widely used in food, medicine, makeup, agricultural and industrial abroad.According to clinical report, current beta-cyclodextrin inclusion compound technology is mainly used in Oleum Cinnamomi, borneol, volatile oil, allicin, Bulbus Allii quintessence oil, Rhizoma Atractylodis oil, zedoary turmeric oil, litsea cubeba oil, angelica essential oil, the preparation research of Tumeric volatilization wet goods inclusion compound, but because beta-cyclodextrin is at C2, intramolecular hydrogen bond is formed between C3 hydroxyl, therefore the solubleness in water lower (1.85g/100mL), limit the application of beta-cyclodextrin, therefore in recent years, investigator carries out structural modification to beta-cyclodextrin, prepare multiple beta-cyclodextrin derivative, these derivatives have the physico-chemical property different from natural beta-cyclodextrin and clathration because of it and expand the range of application of beta-cyclodextrin.
Hydroxypropyl-beta-cyclodextrin (HPCD) is the chemical derivative of cyclodextrin, it is not only the same with beta-cyclodextrin, excellent tetra-inclusion complex is had to chemical compound lot, can improve by the stability of envelope material, and water-soluble height, to improve by the release rate of envelope object and bioavailability.Having greatly in food flavor(ing) spices is all oiliness volatile component, and embedding can improve its stability later, is beneficial to accumulating and application.Some food nutrient compositions, such as, liposoluble vitamin and unsaturated fatty acids, be not only insoluble in water, also easy oxidative degradation, can partly or entirely overcome the above problems with cyclodextrin embedding.In " Chinese Pharmacopoeia ", indissoluble, water-fast medicine account for 1/3, and solubleness is to improve drug effect in water to increase these medicines, significant.Utilizing the mating reaction of beta-cyclodextrin or derivatives thereof and medicine to increase the water-soluble of medicine, is the method for extensively research for many years.And the introducing of hydroxypropyl opens the intramolecular hydrogen bond of beta-cyclodextrin, water-soluble raising (>50%) greatly, and HPCD thermostability is high, hemolytic action is low, be low toxicity, safe and effective solubilizing agent, be considered to potential excipient substance and foodstuff additive.And the average substitution degree of hydroxypropyl-beta-cyclodextrin is the important indicator characterizing hydroxypropyl-beta-cyclodextrin, its numerical range is generally between 0-21, and the hemolytic of hydroxypropyl-beta-cyclodextrin is relevant with substitution value size, and substitution value is lower, and hemolytic is larger.About the preparation of HPCD, have some relevant reports both at home and abroad, but be mostly continue to use method the earliest or experimentally situation carried out part and improved.Traditional preparation method's yield is lower, consuming time, have impact on preparation efficiency.
CN102040675 discloses a kind of preparation method of hydroxypropyl-beta-cyclodextrin, adopts sodium hydroxide, beta-cyclodextrin and 1,2 epoxy prapane to be raw material, but the hydroxypropyl-beta-cyclodextrin yield adopting the present invention to obtain is lower, and product substitution value is higher.
Summary of the invention
In order to overcome in prior art, to produce hydroxypropyl-beta-cyclodextrin productive rate low, the problems such as product substitution value is higher, the invention provides a kind of production method of hydroxypropyl-beta-cyclodextrin, it is high that the hydroxypropyl-beta-cyclodextrin obtained has yield, the advantages such as substitution value is low, and hemolytic is large.Concrete technical scheme is:
A preparation method for hydroxypropyl-beta-cyclodextrin, its step comprises:
(1) modulating starch quality concentration with distilled water is the starch milk of 12%-14%, at 75-85 DEG C, stir 30-50 minute; Again temperature is adjusted to 40-45 DEG C, the concentration adding 9-13 Ge Meihuo unit according to every gram of starch adds cyclomaltodextrin glucanotransferase, add organic solvent again: addition is after every gram of starch adds the hexanaphthene of 0.8-1.1mL, conversion reaction 6-7 hour, adjust ph 8-9 in conversion process, after filtration, filtrate adopts the means of crystallization to obtain beta-cyclodextrin product;
(2) be that 20% ~ 25% aqueous sodium hydroxide solution is heated to 50-55 DEG C by mass concentration, slowly add the beta-cyclodextrin that step (1) obtains while stirring, continue to stir until beta-cyclodextrin dissolves completely, cool to room temperature, evenly 1 is dripped in 3h-3.5h while stirring under water-bath, 2-propylene oxide 30-35ml, temperature controls at 22 ~ 24 DEG C by dropping process, dropwises rear continuation and stirs 3-5 hour; Wherein the mol ratio of sodium hydroxide, beta-cyclodextrin and 1,2 epoxy prapane is 4:2-3:1-2;
(3) the reactant hydrochloric acid that step (2) obtains is neutralized, regulate and make its pH=7;
(4) underpressure distillation is carried out to the reaction solution that step (3) obtains, the soup compound dissolve with ethanol obtained, stir, filter, then carry out underpressure distillation and obtain underflow;
(5) step (4) gained underflow imported in spray-drier, temperature controls, at 5 ~ 10 DEG C, to obtain white amorphous powder hydroxypropyl-beta-cyclodextrin.
Wherein, the starch in step (1) is yam starch;
Wherein, the organic solvent in step (1) is hexanaphthene;
Wherein, the concentration that in step (1), every gram of starch adds 10-12 Ge Meihuo unit adds cyclomaltodextrin glucanotransferase, and the concentration that preferably every gram of starch adds 11 Ge Meihuo units adds cyclomaltodextrin glucanotransferase.
Wherein, in step (2), aqueous sodium hydroxide solution mass concentration is 21% ~ 24%; Preferred mass concentration is 23%;
Wherein, in step (2), the mol ratio of sodium hydroxide, beta-cyclodextrin and 1,2 epoxy prapane is 4:2:1;
The preparation method of the present invention by adjustment beta-cyclodextrin and then the performance of adjustment beta-cyclodextrin; Additionally by adjustment proportioning raw materials and design parameter, it is low that obtained hydroxypropyl-beta-cyclodextrin has substitution value, the advantage that productive rate is high.
Embodiment
Below in conjunction with the embodiment of the application, the technical scheme of the application is described in detail, but following embodiment is only understand the present invention, and the application can not be limited, embodiment in the application and the feature in embodiment can combine mutually, and the multitude of different ways that the application can be defined by the claims and cover is implemented.
Embodiment 1
(1) modulating yam starch mass concentration with distilled water is the starch milk of 12%, stirs 30 minutes at 75 DEG C; Again temperature is adjusted to 40 DEG C, the concentration adding 9 Ge Meihuo units according to every gram of starch adds cyclomaltodextrin glucanotransferase, add hexanaphthene again: addition is after every gram of starch adds the hexanaphthene of 0.8mL, conversion reaction 6 hours, adjust ph 8 in conversion process, after filtration, filtrate adopts the means of crystallization to obtain beta-cyclodextrin product;
(2) be that 20% aqueous sodium hydroxide solution is heated to 50 DEG C by mass concentration, slowly add the beta-cyclodextrin that step (1) obtains while stirring, continue to stir until beta-cyclodextrin dissolves completely, cool to room temperature, evenly 1 is dripped in 3h while stirring under water-bath, 2-propylene oxide 30ml, temperature controls at 22 DEG C by dropping process, dropwises rear continuation stirring 3 hours; Wherein the mol ratio of sodium hydroxide, beta-cyclodextrin and 1,2 epoxy prapane is 4:2:1;
(3) the reactant hydrochloric acid that step (2) obtains is neutralized, regulate and make its pH=7;
(4) underpressure distillation is carried out to the reaction solution that step (3) obtains, the soup compound dissolve with ethanol obtained, stir, filter, then carry out underpressure distillation and obtain underflow;
(5) step (4) gained underflow imported in spray-drier, temperature controls, at 5 DEG C, to obtain white amorphous powder hydroxypropyl-beta-cyclodextrin.
Embodiment 2
(1) modulating yam starch mass concentration with distilled water is the starch milk of 14%, stirs 50 minutes at 85 DEG C; Again temperature is adjusted to 45 DEG C, the concentration adding 13 Ge Meihuo units according to every gram of starch adds cyclomaltodextrin glucanotransferase, add hexanaphthene again: addition is after every gram of starch adds the hexanaphthene of 1.1mL, conversion reaction 7 hours, adjust ph 9 in conversion process, after filtration, filtrate adopts the means of crystallization to obtain beta-cyclodextrin product;
(2) be that 25% aqueous sodium hydroxide solution is heated to 55 DEG C by mass concentration, slowly add the beta-cyclodextrin that step (1) obtains while stirring, continue to stir until beta-cyclodextrin dissolves completely, cool to room temperature, evenly 1 is dripped in 3.5h while stirring under water-bath, 2-propylene oxide 35ml, temperature controls at 24 DEG C by dropping process, dropwises rear continuation stirring 5 hours; Wherein the mol ratio of sodium hydroxide, beta-cyclodextrin and 1,2 epoxy prapane is 4:3:2;
(3) the reactant hydrochloric acid that step (2) obtains is neutralized, regulate and make its pH=7;
(4) underpressure distillation is carried out to the reaction solution that step (3) obtains, the soup compound dissolve with ethanol obtained, stir, filter, then carry out underpressure distillation and obtain underflow;
(5) step (4) gained underflow imported in spray-drier, temperature controls, at 10 DEG C, to obtain white amorphous powder hydroxypropyl-beta-cyclodextrin.
Embodiment 3
(1) modulating yam starch mass concentration with distilled water is the starch milk of 13%, stirs 40 minutes at 80 DEG C; Again temperature is adjusted to 42 DEG C, the concentration adding 10 Ge Meihuo units according to every gram of starch adds cyclomaltodextrin glucanotransferase, add hexanaphthene again: addition is after every gram of starch adds the hexanaphthene of 1.0mL, conversion reaction 6 hours, adjust ph 8 in conversion process, after filtration, filtrate adopts the means of crystallization to obtain beta-cyclodextrin product;
(2) be that 23% aqueous sodium hydroxide solution is heated to 53 DEG C by mass concentration, slowly add the beta-cyclodextrin that step (1) obtains while stirring, continue to stir until beta-cyclodextrin dissolves completely, cool to room temperature, evenly 1 is dripped in 3.2h while stirring under water-bath, 2-propylene oxide 33ml, temperature controls at 23 DEG C by dropping process, dropwises rear continuation stirring 4 hours; Wherein the mol ratio of sodium hydroxide, beta-cyclodextrin and 1,2 epoxy prapane is 4:2:2;
(3) the reactant hydrochloric acid that step (2) obtains is neutralized, regulate and make its pH=7;
(4) underpressure distillation is carried out to the reaction solution that step (3) obtains, the soup compound dissolve with ethanol obtained, stir, filter, then carry out underpressure distillation and obtain underflow;
(5) step (4) gained underflow imported in spray-drier, temperature controls, at 8 DEG C, to obtain white amorphous powder hydroxypropyl-beta-cyclodextrin.
Embodiment 4
(1) modulating yam starch mass concentration with distilled water is the starch milk of 12%, stirs 30 minutes at 75 DEG C; Again temperature is adjusted to 40 DEG C, the concentration adding 11 Ge Meihuo units according to every gram of starch adds cyclomaltodextrin glucanotransferase, add hexanaphthene again: addition is after every gram of starch adds the hexanaphthene of 0.8mL, conversion reaction 6 hours, adjust ph 8 in conversion process, after filtration, filtrate adopts the means of crystallization to obtain beta-cyclodextrin product;
(2) be that 20% aqueous sodium hydroxide solution is heated to 50 DEG C by mass concentration, slowly add the beta-cyclodextrin that step (1) obtains while stirring, continue to stir until beta-cyclodextrin dissolves completely, cool to room temperature, evenly 1 is dripped in 3h while stirring under water-bath, 2-propylene oxide 30ml, temperature controls at 22 DEG C by dropping process, dropwises rear continuation stirring 3 hours; Wherein the mol ratio of sodium hydroxide, beta-cyclodextrin and 1,2 epoxy prapane is 4:2:1;
(3) the reactant hydrochloric acid that step (2) obtains is neutralized, regulate and make its pH=7;
(4) underpressure distillation is carried out to the reaction solution that step (3) obtains, the soup compound dissolve with ethanol obtained, stir, filter, then carry out underpressure distillation and obtain underflow;
(5) step (4) gained underflow imported in spray-drier, temperature controls, at 5 DEG C, to obtain white amorphous powder hydroxypropyl-beta-cyclodextrin.
Embodiment 5
(1) modulating yam starch mass concentration with distilled water is the starch milk of 12%, stirs 30 minutes at 75 DEG C; Again temperature is adjusted to 40 DEG C, the concentration adding 11 Ge Meihuo units according to every gram of starch adds cyclomaltodextrin glucanotransferase, add hexanaphthene again: addition is after every gram of starch adds the hexanaphthene of 0.8mL, conversion reaction 6 hours, adjust ph 8 in conversion process, after filtration, filtrate adopts the means of crystallization to obtain beta-cyclodextrin product;
(2) be that 23% aqueous sodium hydroxide solution is heated to 50 DEG C by mass concentration, slowly add the beta-cyclodextrin that step (1) obtains while stirring, continue to stir until beta-cyclodextrin dissolves completely, cool to room temperature, evenly 1 is dripped in 3h while stirring under water-bath, 2-propylene oxide 30ml, temperature controls at 22 DEG C by dropping process, dropwises rear continuation stirring 3 hours; Wherein the mol ratio of sodium hydroxide, beta-cyclodextrin and 1,2 epoxy prapane is 4:2:1;
(3) the reactant hydrochloric acid that step (2) obtains is neutralized, regulate and make its pH=7;
(4) underpressure distillation is carried out to the reaction solution that step (3) obtains, the soup compound dissolve with ethanol obtained, stir, filter, then carry out underpressure distillation and obtain underflow;
(5) step (4) gained underflow imported in spray-drier, temperature controls, at 5 DEG C, to obtain white amorphous powder hydroxypropyl-beta-cyclodextrin.
Embodiment 6
(1) modulating yam starch mass concentration with distilled water is the starch milk of 12%, stirs 30 minutes at 75 DEG C; Again temperature is adjusted to 40 DEG C, the concentration adding 9 Ge Meihuo units according to every gram of starch adds cyclomaltodextrin glucanotransferase, add hexanaphthene again: addition is after every gram of starch adds the hexanaphthene of 0.8mL, conversion reaction 6 hours, adjust ph 8 in conversion process, after filtration, filtrate adopts the means of crystallization to obtain beta-cyclodextrin product;
(2) be that 20% aqueous sodium hydroxide solution is heated to 50 DEG C by mass concentration, slowly add the beta-cyclodextrin that step (1) obtains while stirring, continue to stir until beta-cyclodextrin dissolves completely, cool to room temperature, evenly 1 is dripped in 3h while stirring under water-bath, 2-propylene oxide 30ml, temperature controls at 22 DEG C by dropping process, dropwises rear continuation stirring 3 hours; Wherein the mol ratio of sodium hydroxide, beta-cyclodextrin and 1,2 epoxy prapane is 4:3:2;
(3) the reactant hydrochloric acid that step (2) obtains is neutralized, regulate and make its pH=7;
(4) underpressure distillation is carried out to the reaction solution that step (3) obtains, the soup compound dissolve with ethanol obtained, stir, filter, then carry out underpressure distillation and obtain underflow;
(5) step (4) gained underflow imported in spray-drier, temperature controls, at 5 DEG C, to obtain white amorphous powder hydroxypropyl-beta-cyclodextrin.
Comparative example 1
(1) modulating W-Gum mass concentration with distilled water is the starch milk of 12%, stirs 30 minutes at 75 DEG C; Again temperature is adjusted to 40 DEG C, the concentration adding 9 Ge Meihuo units according to every gram of starch adds cyclomaltodextrin glucanotransferase, add hexanaphthene again: addition is after every gram of starch adds the hexanaphthene of 0.8mL, conversion reaction 6 hours, adjust ph 8 in conversion process, after filtration, filtrate adopts the means of crystallization to obtain beta-cyclodextrin product;
(2) be that 20% aqueous sodium hydroxide solution is heated to 50 DEG C by mass concentration, slowly add the beta-cyclodextrin that step (1) obtains while stirring, continue to stir until beta-cyclodextrin dissolves completely, cool to room temperature, evenly 1 is dripped in 3h while stirring under water-bath, 2-propylene oxide 30ml, temperature controls at 22 DEG C by dropping process, dropwises rear continuation stirring 3 hours; Wherein the mol ratio of sodium hydroxide, beta-cyclodextrin and 1,2 epoxy prapane is 4:2:1;
(3) the reactant hydrochloric acid that step (2) obtains is neutralized, regulate and make its pH=7;
(4) underpressure distillation is carried out to the reaction solution that step (3) obtains, the soup compound dissolve with ethanol obtained, stir, filter, then carry out underpressure distillation and obtain underflow;
(5) step (4) gained underflow imported in spray-drier, temperature controls, at 5 DEG C, to obtain white amorphous powder hydroxypropyl-beta-cyclodextrin.
Comparative example 2
(1) modulating yam starch mass concentration with distilled water is the starch milk of 12%, stirs 30 minutes at 75 DEG C; Again temperature is adjusted to 40 DEG C, the concentration adding 9 Ge Meihuo units according to every gram of starch adds cyclomaltodextrin glucanotransferase, add ethanol again: addition is after every gram of starch adds the ethanol of 0.8mL, conversion reaction 6 hours, adjust ph 8 in conversion process, after filtration, filtrate adopts the means of crystallization to obtain beta-cyclodextrin product;
(2) be that 20% aqueous sodium hydroxide solution is heated to 50 DEG C by mass concentration, slowly add the beta-cyclodextrin that step (1) obtains while stirring, continue to stir until beta-cyclodextrin dissolves completely, cool to room temperature, evenly 1 is dripped in 3h while stirring under water-bath, 2-propylene oxide 30ml, temperature controls at 22 DEG C by dropping process, dropwises rear continuation stirring 3 hours; Wherein the mol ratio of sodium hydroxide, beta-cyclodextrin and 1,2 epoxy prapane is 4:2:1;
(3) the reactant hydrochloric acid that step (2) obtains is neutralized, regulate and make its pH=7;
(4) underpressure distillation is carried out to the reaction solution that step (3) obtains, the soup compound dissolve with ethanol obtained, stir, filter, then carry out underpressure distillation and obtain underflow;
(5) step (4) gained underflow imported in spray-drier, temperature controls, at 5 DEG C, to obtain white amorphous powder hydroxypropyl-beta-cyclodextrin.
Comparative example 3
(1) modulating yam starch mass concentration with distilled water is the starch milk of 12%, stirs 30 minutes at 75 DEG C; Again temperature is adjusted to 40 DEG C, the concentration adding 9 Ge Meihuo units according to every gram of starch adds cyclomaltodextrin glucanotransferase, add hexanaphthene again: addition is after every gram of starch adds the hexanaphthene of 0.8mL, conversion reaction 6 hours, adjust ph 8 in conversion process, after filtration, filtrate adopts the means of crystallization to obtain beta-cyclodextrin product;
(2) be that 18% aqueous sodium hydroxide solution is heated to 50 DEG C by mass concentration, slowly add the beta-cyclodextrin that step (1) obtains while stirring, continue to stir until beta-cyclodextrin dissolves completely, cool to room temperature, evenly 1 is dripped in 3h while stirring under water-bath, 2-propylene oxide 30ml, temperature controls at 22 DEG C by dropping process, dropwises rear continuation stirring 3 hours; Wherein the mol ratio of sodium hydroxide, beta-cyclodextrin and 1,2 epoxy prapane is 4:2:1;
(3) the reactant hydrochloric acid that step (2) obtains is neutralized, regulate and make its pH=7;
(4) underpressure distillation is carried out to the reaction solution that step (3) obtains, the soup compound dissolve with ethanol obtained, stir, filter, then carry out underpressure distillation and obtain underflow;
(5) step (4) gained underflow imported in spray-drier, temperature controls, at 5 DEG C, to obtain white amorphous powder hydroxypropyl-beta-cyclodextrin.
Comparative example 4
(1) modulating yam starch mass concentration with distilled water is the starch milk of 12%, stirs 30 minutes at 75 DEG C; Again temperature is adjusted to 40 DEG C, the concentration adding 9 Ge Meihuo units according to every gram of starch adds cyclomaltodextrin glucanotransferase, add hexanaphthene again: addition is after every gram of starch adds the hexanaphthene of 0.8mL, conversion reaction 6 hours, adjust ph 8 in conversion process, after filtration, filtrate adopts the means of crystallization to obtain beta-cyclodextrin product;
(2) be that 20% aqueous sodium hydroxide solution is heated to 50 DEG C by mass concentration, slowly add the beta-cyclodextrin that step (1) obtains while stirring, continue to stir until beta-cyclodextrin dissolves completely, cool to room temperature, evenly 1 is dripped in 3h while stirring under water-bath, 2-propylene oxide 30ml, temperature controls at 22 DEG C by dropping process, dropwises rear continuation stirring 3 hours; Wherein the mol ratio of sodium hydroxide, beta-cyclodextrin and 1,2 epoxy prapane is 9:1:8;
(3) the reactant hydrochloric acid that step (2) obtains is neutralized, regulate and make its pH=7;
(4) underpressure distillation is carried out to the reaction solution that step (3) obtains, the soup compound dissolve with ethanol obtained, stir, filter, then carry out underpressure distillation and obtain underflow;
(5) step (4) gained underflow imported in spray-drier, temperature controls, at 5 DEG C, to obtain white amorphous powder hydroxypropyl-beta-cyclodextrin.
The method that substitution value Johnson measures light propyl group starch is carried out.Get 0.3 μ g/L sample lmg in tool plug test tube, add the 8mL vitriol oil, boiling water bath heating 3min, be cooled to 5 DEG C immediately, then add the ninidrine solution 0.5mL of 15 μ g/L, shake up, put constant temperature 100min in 25 DEG C of water-baths and make colour developing, measure under 595nm with spectrophotometer, and try to achieve substitution value with propylene glycol standard curve control.
Table 1 embodiment 1-3 and comparative example 1-7 product analysis result
| Substitution value | Productive rate (%) | |
| Embodiment 1 | 3.5 | 87 |
| Embodiment 2 | 3.7 | 89 |
| Embodiment 3 | 3.21 | 88 |
| Embodiment 4 | 3.3 | 90 |
| Embodiment 5 | 3.12 | 92 |
| Embodiment 6 | 3.6 | 86 |
| Comparative example 1 | 4.5 | 82.5 |
| Comparative example 2 | 5.6 | 78.8 |
| Comparative example 3 | 4.7 | 82.3 |
| Comparative example 4 | 5.2 | 74 |
As can be seen from Table 1, adopt yam starch to be raw material and adopt W-Gum to be that the substitution value of the hydroxypropyl-beta-cyclodextrin that raw material obtains and product yield have bigger difference, yam starch is that the substitution value of the hydroxypropyl-beta-cyclodextrin that raw material obtains and product yield performance are excellent; Adopt hexanaphthene to be organic solvent and adopt ethanol to be that the substitution value of the hydroxypropyl-beta-cyclodextrin that organic solvent obtains and product yield have bigger difference, hexanaphthene is that the substitution value of the hydroxypropyl-beta-cyclodextrin that organic solvent obtains and product yield performance are excellent; By embodiment 1 and embodiment 4, the concentration that every gram of starch adds how many Ge Meihuo unit adds cyclomaltodextrin glucanotransferase has considerable influence to final product performance, when the concentration that every gram of starch adds 11 Ge Meihuo units adds cyclomaltodextrin glucanotransferase, no matter be that product substitution value and product yield all have a significant improvement.By embodiment 4 and embodiment 5, aqueous sodium hydroxide solution mass concentration has considerable influence to final product performance, when aqueous sodium hydroxide solution mass concentration is 23%, be no matter that product substitution value is compared other aqueous sodium hydroxide solution mass concentrations and all had a significant improvement with product yield.By embodiment 1 and embodiment 6 and comparative example 4, the proportionlity between raw material has a great impact product, and found by research, the mol ratio of sodium hydroxide, beta-cyclodextrin and 1,2 epoxy prapane is 4:2-3:1-2; When being especially in 4:2:1, product substitution value and product yield all have a significant improvement.
Comparative example 5
(1) etherification reaction: be that 10% aqueous sodium hydroxide solution is cooled to 5 DEG C by mass concentration, add beta-cyclodextrin, slowly 1 is dripped after solid is entirely molten, 2-propylene oxide, the mol ratio of sodium hydroxide, beta-cyclodextrin and 1,2 epoxy prapane is 9:1:7.5, temperature is controlled at 5 DEG C in dropping process, time for adding 3.5 hours, dropwise rear continuation stirring 3 hours, gained reaction solution is for subsequent use;
(2) neutralize: in step (1) gained reaction solution, drip concentrated hydrochloric acid adjust ph to 7.1, gained solution for standby;
(3) decolour: in step (2) gained solution, add gac 20g, temperature control 20 DEG C, stir after 30 minutes, filter carbon removal, filtrate is for subsequent use;
(4) desalting purifying: step (3) gained filtrate is carried out nanofiltration desalination, as nanofiltration liquid specific conductivity≤650 μ s/cm, nanofiltration completes, and gained feed liquid is for subsequent use;
(5) resin purification: step (4) gained feed liquid is crossed macroporous resin, flow velocity 1.0BV/h, as feed liquid specific conductivity≤120 μ s/cm, namely complete separation, gained feed liquid is for subsequent use;
(6) spraying dry: step (5) gained feed liquid imported in spray-drier, temperature controls, at 5 DEG C, to obtain white amorphous powder hydroxypropyl-beta-cyclodextrin.
Table 2 embodiment 1 and comparative example 8 product analysis result
| Substitution value | Productive rate (%) | |
| Embodiment 1 | 3.5 | 87 |
| Comparative example 5 | 5.0 | 84.2 |
These are only the preferred embodiments of the present invention, be not limited to the present invention, to those skilled in the art, the present invention can have various change and conversion.Within the spirit and principles in the present invention all, any amendment done, equivalent replacement, improvement etc., all should be included within protection scope of the present invention.
Claims (4)
1. a preparation method for hydroxypropyl-beta-cyclodextrin, is characterized in that step comprises:
(1) modulating starch quality concentration with distilled water is the starch milk of 12%-14%, at 75-85 DEG C, stir 30-50 minute; Again temperature is adjusted to 40-45 DEG C, the concentration adding 11 Ge Meihuo units according to every gram of starch adds cyclomaltodextrin glucanotransferase, add organic solvent again: addition is after every gram of starch adds the hexanaphthene of 0.8-1.1mL, conversion reaction 6-7 hour, adjust ph 8-9 in conversion process, after filtration, filtrate adopts the means of crystallization to obtain beta-cyclodextrin product;
(2) be that 20% ~ 25% aqueous sodium hydroxide solution is heated to 50-55 DEG C by mass concentration, slowly add the beta-cyclodextrin that step (1) obtains while stirring, continue to stir until beta-cyclodextrin dissolves completely, cool to room temperature, evenly 1 is dripped in 3h-3.5h while stirring under water-bath, 2-propylene oxide 30-35ml, temperature controls at 22 ~ 24 DEG C by dropping process, dropwises rear continuation and stirs 3-5 hour; Wherein the mol ratio of sodium hydroxide, beta-cyclodextrin and 1,2 epoxy prapane is 4:2-3:1-2;
(3) the reactant hydrochloric acid that step (2) obtains is neutralized, regulate and make its pH=7;
(4) underpressure distillation is carried out to the reaction solution that step (3) obtains, the soup compound dissolve with ethanol obtained, stir, filter, then carry out underpressure distillation and obtain underflow;
(5) step (4) gained underflow imported in spray-drier, temperature controls, at 5 ~ 10 DEG C, to obtain white amorphous powder hydroxypropyl-beta-cyclodextrin; Starch wherein in step (1) is yam starch; In step (1), organic solvent is hexanaphthene.
2. method according to claim 1, is characterized in that in step (2), aqueous sodium hydroxide solution mass concentration is 21% ~ 24%.
3. method according to claim 2, is characterized in that in step (2), aqueous sodium hydroxide solution mass concentration is 23%.
4. method according to claim 1, is characterized in that the mol ratio of sodium hydroxide, beta-cyclodextrin and 1,2 epoxy prapane in step (2) is 4:2:1.
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Inventor after: Wang Liping Inventor after: Bi Fangyu Inventor after: Xu Weicheng Inventor after: Wang Zhe Inventor after: Qi Aixia Inventor after: Zhang Lixin Inventor after: Ma Juan Inventor before: Wang Liping Inventor before: Bi Fangyu Inventor before: Xu Weicheng Inventor before: Wang Zhe |