CN104151451A - Preparation method of hydroxypropyl-[beta]-cyclodextrin - Google Patents
Preparation method of hydroxypropyl-[beta]-cyclodextrin Download PDFInfo
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Abstract
The invention discloses a preparation method of hydroxypropyl-[beta]-cyclodextrin. The method includes following steps: (1) preparing a product of [beta]-cyclodextrin; (2) heating a sodium hydroxide aqueous solution with a mass concentration being 20%-25% to 50-55 DEG C, slowly adding the [beta]-cyclodextrin obtained in the step (1) with stirring, continuously performing stirring until the [beta]-cyclodextrin is dissolved completely, cooling the solution to room temperature, dropwisely adding 30-35 ml of 1,2-epoxypropane uniformly in 3-3.5h with stirring in water bath with a temperature being controlled within 22-24 DEG C, and continuously performing stirring for 3-5 hours after the dropwisely adding process is finished, wherein a molar ratio of the sodium hydroxide, the [beta]-cyclodextrin and the 1,2-epoxypropane is 4:2-3:1-2; (3) neutralizing the reactant obtained in the step (2) for adjusting the pH of the reactant to be 7; (4) performing reduced pressure distillation to the reactant obtained in the step (3), dissolving a obtained slurry subject through ethanol, performing a stirring and filtering process and performing the reduced pressure distillation again to obtain a thick slurry; and step (5) feeding the thick slurry to a spray drier with the temperature being controlling within 5-10 DEG C to obtain a white amorphous powder of the hydroxypropyl-[beta]-cyclodextrin. The prepared hydroxypropyl-[beta]-cyclodextrin is low in substitution degree and is high in yield.
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 the general name of one group of oligose being formed by the circular permutation of some D-glucopyranose units.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 is described, early literatures is also called Schardinger dextrin cyclodextrin.
Cyclodextrin Chemistry has obtained the development of advancing by leaps and bounds in two, 30 years in the past.Up to the present, existing many monographs and some long summaries, structure, character and the application of describing cyclodextrin and inclusion compound thereof more than 1400 above patents and thousands of articles.As a kind of simple organic macromolecule, cyclodextrin has and scope all kinds of objects extremely widely, such as organic molecule, mineral ion, title complex rare gas element even, by molecular interaction, forms host-guest inclusion compound.Cyclodextrin and derivative thereof are the important research objects of main-guest chemistry, the inclusion compound forming as the cyclodextrin of main body and transition metal complex effect as object, also referred to as outer coordination sphere compound (secondsphere coordination compound).The preparation of cyclodextrin inclusion compound, structure, character and applied research are important contents of Cyclodextrin Chemistry, in addition, and about modification, polymerization and the Multiple recognition of cyclodextrin are studied also in the ascendant.This respect work can not only provide weak interaction and molecule assembling main body in research supramolecule field, CD derivative or CD polymkeric substance after modifying also can be used as good catalyzer and enzyme model simultaneously, and are widely used in the various fields such as biomimetic chemistry, catalysis and organic synthesis.In addition, cyclodextrin, aspect solubilising, modification and minute subpack of medicine, spices and seasonings, has been shown wide application prospect to common people.
Beta-cyclodextrin (β-cyclodextrin, β-CD) be a kind of of cyclodextrin, that structure by 7 β-Glucopyranoses is by the cyclic oligosaccharide that α-(1,4) glycosidic link is formed by connecting, 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 to inclusion compound, therefore become noticeable a kind of novel inclusion material.Because beta-cyclodextrin solubleness is low, easily crystallization, separation, purification, nontoxicity, readily biodegradable, and also production cost is lower, is widely used in abroad food, medicine, makeup, agricultural and industrial.According to clinical report, beta-cyclodextrin inclusion compound technology is mainly used in Oleum Cinnamomi at present, 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, between C3 hydroxyl, form intramolecular hydrogen bond, so solubleness lower (1.85g/100mL) in water, limited the application of beta-cyclodextrin, therefore in recent years, investigator carries out structural modification to beta-cyclodextrin, prepared multiple beta-cyclodextrin derivative, these derivatives have because of it range of application that physico-chemical property different from natural beta-cyclodextrin and clathration have expanded beta-cyclodextrin.
Hydroxypropyl-beta-cyclodextrin (HPCD) is the chemical derivative of cyclodextrin, it is not only the same with beta-cyclodextrin, chemical compound lot is had to good envelope effect, can improve by the stability of envelope material, and water-soluble height, can improve by the release rate of envelope object and bioavailability.In food flavor(ing) spices, having is greatly all oiliness volatile component, and embedding can improve its stability later, is beneficial to accumulating and application.Some food nutrient compositions, for example, liposoluble vitamin and unsaturated fatty acids, be not only insoluble in water, and 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, increase these medicines solubleness in water to improve drug effect, significant.Utilizing the mating reaction of beta-cyclodextrin or derivatives thereof and medicine to increase the water-soluble of medicine, is the method for broad research for many years.And the intramolecular hydrogen bond of beta-cyclodextrin has been opened in the introducing of hydroxypropyl, water-soluble greatly improve (>50%), 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 an important indicator that characterizes 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, there are some relevant reports both at home and abroad, but are mostly continue to use method the earliest or carried out partly improving according to experiment situation.Traditional preparation method's yield is lower, consuming time, has affected preparation efficiency.
CN102040675 discloses a kind of preparation method of hydroxypropyl-beta-cyclodextrin, and adopting sodium hydroxide, beta-cyclodextrin and 1,2 epoxy prapane is raw material, but the hydroxypropyl-beta-cyclodextrin yield that adopts 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, and it is high that the hydroxypropyl-beta-cyclodextrin obtaining 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) starch milk that is 12%-14% by distilled water modulation starch quality concentration stirs 30-50 minute at 75-85 ℃; Again temperature is adjusted to 40-45 ℃, the concentration that adds 9-13 Ge Meihuo unit according to every gram of starch adds cyclomaltodextrin glucanotransferase, add again organic solvent: addition is that every gram of starch adds after the hexanaphthene of 0.8-1.1mL, conversion reaction 6-7 hour, in conversion process, regulate pH value 8-9, after filtering, filtrate adopts the means of crystallization to obtain beta-cyclodextrin product;
(2) by mass concentration, be that 20%～25% aqueous sodium hydroxide solution is heated to 50-55 ℃, the beta-cyclodextrin that slowly adds while stirring step (1) to obtain, continue to stir until beta-cyclodextrin dissolves completely, cool to room temperature, under water-bath, in 3h-3.5h, evenly drip 1 while stirring, 2-propylene oxide 30-35ml, dropping process is controlled at 22～24 ℃ by temperature, 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) reactant step (2) being obtained neutralizes with hydrochloric acid, regulates and makes its pH=7;
(4) reaction solution step (3) being obtained carries out underpressure distillation, and the soup compound dissolve with ethanol obtaining stirs, and filters, then carries out underpressure distillation and obtain underflow;
(5) step (4) gained underflow is imported in spray-drier, temperature is controlled at 5～10 ℃, obtains 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 11Ge Meihuo unit 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 present invention is by adjusting the preparation method of beta-cyclodextrin and then the performance of adjustment beta-cyclodextrin; By adjusting proportioning raw materials and design parameter, it is low that the hydroxypropyl-beta-cyclodextrin making has substitution value, the advantage that productive rate is high in addition.
Embodiment
Embodiment below in conjunction with the application, technical scheme to the application is described in detail, but following embodiment understands the present invention, and can not limit the application, embodiment and the feature in embodiment in the application 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) starch milk that is 12% by distilled water modulation yam starch mass concentration stirs 30 minutes at 75 ℃; Temperature is adjusted to 40 ℃ again, the concentration that adds 9 Ge Meihuo units according to every gram of starch adds cyclomaltodextrin glucanotransferase, add again hexanaphthene: addition is that every gram of starch adds after the hexanaphthene of 0.8mL, conversion reaction 6 hours, in conversion process, regulate pH value 8, after filtering, filtrate adopts the means of crystallization to obtain beta-cyclodextrin product;
(2) by mass concentration, be that 20% aqueous sodium hydroxide solution is heated to 50 ℃, the beta-cyclodextrin that slowly adds while stirring step (1) to obtain, continue to stir until beta-cyclodextrin dissolves completely, cool to room temperature, under water-bath, in 3h, evenly drip 1 while stirring, 2-propylene oxide 30ml, dropping process is controlled at 22 ℃ by temperature, dropwises rear continuation and stirs 3 hours; Wherein the mol ratio of sodium hydroxide, beta-cyclodextrin and 1,2 epoxy prapane is 4:2:1;
(3) reactant step (2) being obtained neutralizes with hydrochloric acid, regulates and makes its pH=7;
(4) reaction solution step (3) being obtained carries out underpressure distillation, and the soup compound dissolve with ethanol obtaining stirs, and filters, then carries out underpressure distillation and obtain underflow;
(5) step (4) gained underflow is imported in spray-drier, temperature is controlled at 5 ℃, obtains white amorphous powder hydroxypropyl-beta-cyclodextrin.
Embodiment 2
(1) starch milk that is 14% by distilled water modulation yam starch mass concentration stirs 50 minutes at 85 ℃; Temperature is adjusted to 45 ℃ again, the concentration that adds 13Ge Meihuo unit according to every gram of starch adds cyclomaltodextrin glucanotransferase, add again hexanaphthene: addition is that every gram of starch adds after the hexanaphthene of 1.1mL, conversion reaction 7 hours, in conversion process, regulate pH value 9, after filtering, filtrate adopts the means of crystallization to obtain beta-cyclodextrin product;
(2) by mass concentration, be that 25% aqueous sodium hydroxide solution is heated to 55 ℃, the beta-cyclodextrin that slowly adds while stirring step (1) to obtain, continue to stir until beta-cyclodextrin dissolves completely, cool to room temperature, under water-bath, in 3.5h, evenly drip 1 while stirring, 2-propylene oxide 35ml, dropping process is controlled at 24 ℃ by temperature, dropwises rear continuation and stirs 5 hours; Wherein the mol ratio of sodium hydroxide, beta-cyclodextrin and 1,2 epoxy prapane is 4:3:2;
(3) reactant step (2) being obtained neutralizes with hydrochloric acid, regulates and makes its pH=7;
(4) reaction solution step (3) being obtained carries out underpressure distillation, and the soup compound dissolve with ethanol obtaining stirs, and filters, then carries out underpressure distillation and obtain underflow;
(5) step (4) gained underflow is imported in spray-drier, temperature is controlled at 10 ℃, obtains white amorphous powder hydroxypropyl-beta-cyclodextrin.
Embodiment 3
(1) starch milk that is 13% by distilled water modulation yam starch mass concentration stirs 40 minutes at 80 ℃; Temperature is adjusted to 42 ℃ again, the concentration that adds 10Ge Meihuo unit according to every gram of starch adds cyclomaltodextrin glucanotransferase, add again hexanaphthene: addition is that every gram of starch adds after the hexanaphthene of 1.0mL, conversion reaction 6 hours, in conversion process, regulate pH value 8, after filtering, filtrate adopts the means of crystallization to obtain beta-cyclodextrin product;
(2) by mass concentration, be that 23% aqueous sodium hydroxide solution is heated to 53 ℃, the beta-cyclodextrin that slowly adds while stirring step (1) to obtain, continue to stir until beta-cyclodextrin dissolves completely, cool to room temperature, under water-bath, in 3.2h, evenly drip 1 while stirring, 2-propylene oxide 33ml, dropping process is controlled at 23 ℃ by temperature, dropwises rear continuation and stirs 4 hours; Wherein the mol ratio of sodium hydroxide, beta-cyclodextrin and 1,2 epoxy prapane is 4:2:2;
(3) reactant step (2) being obtained neutralizes with hydrochloric acid, regulates and makes its pH=7;
(4) reaction solution step (3) being obtained carries out underpressure distillation, and the soup compound dissolve with ethanol obtaining stirs, and filters, then carries out underpressure distillation and obtain underflow;
(5) step (4) gained underflow is imported in spray-drier, temperature is controlled at 8 ℃, obtains white amorphous powder hydroxypropyl-beta-cyclodextrin.
Embodiment 4
(1) starch milk that is 12% by distilled water modulation yam starch mass concentration stirs 30 minutes at 75 ℃; Temperature is adjusted to 40 ℃ again, the concentration that adds 11Ge Meihuo unit according to every gram of starch adds cyclomaltodextrin glucanotransferase, add again hexanaphthene: addition is that every gram of starch adds after the hexanaphthene of 0.8mL, conversion reaction 6 hours, in conversion process, regulate pH value 8, after filtering, filtrate adopts the means of crystallization to obtain beta-cyclodextrin product;
(2) by mass concentration, be that 20% aqueous sodium hydroxide solution is heated to 50 ℃, the beta-cyclodextrin that slowly adds while stirring step (1) to obtain, continue to stir until beta-cyclodextrin dissolves completely, cool to room temperature, under water-bath, in 3h, evenly drip 1 while stirring, 2-propylene oxide 30ml, dropping process is controlled at 22 ℃ by temperature, dropwises rear continuation and stirs 3 hours; Wherein the mol ratio of sodium hydroxide, beta-cyclodextrin and 1,2 epoxy prapane is 4:2:1;
(3) reactant step (2) being obtained neutralizes with hydrochloric acid, regulates and makes its pH=7;
(4) reaction solution step (3) being obtained carries out underpressure distillation, and the soup compound dissolve with ethanol obtaining stirs, and filters, then carries out underpressure distillation and obtain underflow;
(5) step (4) gained underflow is imported in spray-drier, temperature is controlled at 5 ℃, obtains white amorphous powder hydroxypropyl-beta-cyclodextrin.
Embodiment 5
(1) starch milk that is 12% by distilled water modulation yam starch mass concentration stirs 30 minutes at 75 ℃; Temperature is adjusted to 40 ℃ again, the concentration that adds 11Ge Meihuo unit according to every gram of starch adds cyclomaltodextrin glucanotransferase, add again hexanaphthene: addition is that every gram of starch adds after the hexanaphthene of 0.8mL, conversion reaction 6 hours, in conversion process, regulate pH value 8, after filtering, filtrate adopts the means of crystallization to obtain beta-cyclodextrin product;
(2) by mass concentration, be that 23% aqueous sodium hydroxide solution is heated to 50 ℃, the beta-cyclodextrin that slowly adds while stirring step (1) to obtain, continue to stir until beta-cyclodextrin dissolves completely, cool to room temperature, under water-bath, in 3h, evenly drip 1 while stirring, 2-propylene oxide 30ml, dropping process is controlled at 22 ℃ by temperature, dropwises rear continuation and stirs 3 hours; Wherein the mol ratio of sodium hydroxide, beta-cyclodextrin and 1,2 epoxy prapane is 4:2:1;
(3) reactant step (2) being obtained neutralizes with hydrochloric acid, regulates and makes its pH=7;
(4) reaction solution step (3) being obtained carries out underpressure distillation, and the soup compound dissolve with ethanol obtaining stirs, and filters, then carries out underpressure distillation and obtain underflow;
(5) step (4) gained underflow is imported in spray-drier, temperature is controlled at 5 ℃, obtains white amorphous powder hydroxypropyl-beta-cyclodextrin.
Embodiment 6
(1) starch milk that is 12% by distilled water modulation yam starch mass concentration stirs 30 minutes at 75 ℃; Temperature is adjusted to 40 ℃ again, the concentration that adds 9 Ge Meihuo units according to every gram of starch adds cyclomaltodextrin glucanotransferase, add again hexanaphthene: addition is that every gram of starch adds after the hexanaphthene of 0.8mL, conversion reaction 6 hours, in conversion process, regulate pH value 8, after filtering, filtrate adopts the means of crystallization to obtain beta-cyclodextrin product;
(2) by mass concentration, be that 20% aqueous sodium hydroxide solution is heated to 50 ℃, the beta-cyclodextrin that slowly adds while stirring step (1) to obtain, continue to stir until beta-cyclodextrin dissolves completely, cool to room temperature, under water-bath, in 3h, evenly drip 1 while stirring, 2-propylene oxide 30ml, dropping process is controlled at 22 ℃ by temperature, dropwises rear continuation and stirs 3 hours; Wherein the mol ratio of sodium hydroxide, beta-cyclodextrin and 1,2 epoxy prapane is 4:3:2;
(3) reactant step (2) being obtained neutralizes with hydrochloric acid, regulates and makes its pH=7;
(4) reaction solution step (3) being obtained carries out underpressure distillation, and the soup compound dissolve with ethanol obtaining stirs, and filters, then carries out underpressure distillation and obtain underflow;
(5) step (4) gained underflow is imported in spray-drier, temperature is controlled at 5 ℃, obtains white amorphous powder hydroxypropyl-beta-cyclodextrin.
Comparative example 1
(1) starch milk that is 12% by distilled water modulation W-Gum mass concentration stirs 30 minutes at 75 ℃; Temperature is adjusted to 40 ℃ again, the concentration that adds 9 Ge Meihuo units according to every gram of starch adds cyclomaltodextrin glucanotransferase, add again hexanaphthene: addition is that every gram of starch adds after the hexanaphthene of 0.8mL, conversion reaction 6 hours, in conversion process, regulate pH value 8, after filtering, filtrate adopts the means of crystallization to obtain beta-cyclodextrin product;
(2) by mass concentration, be that 20% aqueous sodium hydroxide solution is heated to 50 ℃, the beta-cyclodextrin that slowly adds while stirring step (1) to obtain, continue to stir until beta-cyclodextrin dissolves completely, cool to room temperature, under water-bath, in 3h, evenly drip 1 while stirring, 2-propylene oxide 30ml, dropping process is controlled at 22 ℃ by temperature, dropwises rear continuation and stirs 3 hours; Wherein the mol ratio of sodium hydroxide, beta-cyclodextrin and 1,2 epoxy prapane is 4:2:1;
(3) reactant step (2) being obtained neutralizes with hydrochloric acid, regulates and makes its pH=7;
(4) reaction solution step (3) being obtained carries out underpressure distillation, and the soup compound dissolve with ethanol obtaining stirs, and filters, then carries out underpressure distillation and obtain underflow;
(5) step (4) gained underflow is imported in spray-drier, temperature is controlled at 5 ℃, obtains white amorphous powder hydroxypropyl-beta-cyclodextrin.
Comparative example 2
(1) starch milk that is 12% by distilled water modulation yam starch mass concentration stirs 30 minutes at 75 ℃; Temperature is adjusted to 40 ℃ again, the concentration that adds 9 Ge Meihuo units according to every gram of starch adds cyclomaltodextrin glucanotransferase, add again ethanol: addition is that every gram of starch adds after the ethanol of 0.8mL, conversion reaction 6 hours, in conversion process, regulate pH value 8, after filtering, filtrate adopts the means of crystallization to obtain beta-cyclodextrin product;
(2) by mass concentration, be that 20% aqueous sodium hydroxide solution is heated to 50 ℃, the beta-cyclodextrin that slowly adds while stirring step (1) to obtain, continue to stir until beta-cyclodextrin dissolves completely, cool to room temperature, under water-bath, in 3h, evenly drip 1 while stirring, 2-propylene oxide 30ml, dropping process is controlled at 22 ℃ by temperature, dropwises rear continuation and stirs 3 hours; Wherein the mol ratio of sodium hydroxide, beta-cyclodextrin and 1,2 epoxy prapane is 4:2:1;
(3) reactant step (2) being obtained neutralizes with hydrochloric acid, regulates and makes its pH=7;
(4) reaction solution step (3) being obtained carries out underpressure distillation, and the soup compound dissolve with ethanol obtaining stirs, and filters, then carries out underpressure distillation and obtain underflow;
(5) step (4) gained underflow is imported in spray-drier, temperature is controlled at 5 ℃, obtains white amorphous powder hydroxypropyl-beta-cyclodextrin.
Comparative example 3
(1) starch milk that is 12% by distilled water modulation yam starch mass concentration stirs 30 minutes at 75 ℃; Temperature is adjusted to 40 ℃ again, the concentration that adds 9 Ge Meihuo units according to every gram of starch adds cyclomaltodextrin glucanotransferase, add again hexanaphthene: addition is that every gram of starch adds after the hexanaphthene of 0.8mL, conversion reaction 6 hours, in conversion process, regulate pH value 8, after filtering, filtrate adopts the means of crystallization to obtain beta-cyclodextrin product;
(2) by mass concentration, be that 18% aqueous sodium hydroxide solution is heated to 50 ℃, the beta-cyclodextrin that slowly adds while stirring step (1) to obtain, continue to stir until beta-cyclodextrin dissolves completely, cool to room temperature, under water-bath, in 3h, evenly drip 1 while stirring, 2-propylene oxide 30ml, dropping process is controlled at 22 ℃ by temperature, dropwises rear continuation and stirs 3 hours; Wherein the mol ratio of sodium hydroxide, beta-cyclodextrin and 1,2 epoxy prapane is 4:2:1;
(3) reactant step (2) being obtained neutralizes with hydrochloric acid, regulates and makes its pH=7;
(4) reaction solution step (3) being obtained carries out underpressure distillation, and the soup compound dissolve with ethanol obtaining stirs, and filters, then carries out underpressure distillation and obtain underflow;
(5) step (4) gained underflow is imported in spray-drier, temperature is controlled at 5 ℃, obtains white amorphous powder hydroxypropyl-beta-cyclodextrin.
Comparative example 4
(1) starch milk that is 12% by distilled water modulation yam starch mass concentration stirs 30 minutes at 75 ℃; Temperature is adjusted to 40 ℃ again, the concentration that adds 9 Ge Meihuo units according to every gram of starch adds cyclomaltodextrin glucanotransferase, add again hexanaphthene: addition is that every gram of starch adds after the hexanaphthene of 0.8mL, conversion reaction 6 hours, in conversion process, regulate pH value 8, after filtering, filtrate adopts the means of crystallization to obtain beta-cyclodextrin product;
(2) by mass concentration, be that 20% aqueous sodium hydroxide solution is heated to 50 ℃, the beta-cyclodextrin that slowly adds while stirring step (1) to obtain, continue to stir until beta-cyclodextrin dissolves completely, cool to room temperature, under water-bath, in 3h, evenly drip 1 while stirring, 2-propylene oxide 30ml, dropping process is controlled at 22 ℃ by temperature, dropwises rear continuation and stirs 3 hours; Wherein the mol ratio of sodium hydroxide, beta-cyclodextrin and 1,2 epoxy prapane is 9:1:8;
(3) reactant step (2) being obtained neutralizes with hydrochloric acid, regulates and makes its pH=7;
(4) reaction solution step (3) being obtained carries out underpressure distillation, and the soup compound dissolve with ethanol obtaining stirs, and filters, then carries out underpressure distillation and obtain underflow;
(5) step (4) gained underflow is imported in spray-drier, temperature is controlled at 5 ℃, obtains white amorphous powder hydroxypropyl-beta-cyclodextrin.
Substitution value is undertaken by the method that Johnson measures light propyl group starch.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 immediately 5 ℃, then the ninidrine solution 0.5mL that adds 15 μ g/L, shakes up, and puts constant temperature 100min in 25 ℃ of water-baths and makes colour developing, with spectrophotometer, under 595nm, measure, and contrast and try to achieve substitution value with propylene glycol typical curve.
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, to adopt yam starch be raw material with adopting W-Gum is that substitution value and the product yield of the hydroxypropyl-beta-cyclodextrin that makes of raw material has bigger difference, and yam starch is that substitution value and the product yield performance of the hydroxypropyl-beta-cyclodextrin that makes of raw material is excellent; To adopt hexanaphthene be organic solvent with adopting ethanol is that substitution value and the product yield of the hydroxypropyl-beta-cyclodextrin that makes of organic solvent has bigger difference, and hexanaphthene is that substitution value and the product yield performance of the hydroxypropyl-beta-cyclodextrin that makes of organic solvent is excellent; By embodiment 1 and embodiment 4, the concentration that every gram of starch adds how many Ge Meihuo units adds cyclomaltodextrin glucanotransferase to have considerable influence to final product performance, when the concentration that adds 11Ge Meihuo unit when every gram of starch 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, by research, finds, the mol ratio of sodium hydroxide, beta-cyclodextrin and 1,2 epoxy prapane is 4:2-3:1-2; Especially when 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 ℃ by mass concentration, add beta-cyclodextrin, after solid is entirely molten, slowly drip 1,2-propylene oxide, the mol ratio of sodium hydroxide, beta-cyclodextrin and 1,2 epoxy prapane is 9:1:7.5, in dropping process, temperature is controlled to 5 ℃, time for adding 3.5 hours, dropwises rear continuation and stirs 3 hours, and gained reaction solution is standby;
(2) neutralization: drip concentrated hydrochloric acid adjusting pH value to 7.1, gained solution for standby in step (1) gained reaction solution;
(3) decolouring: add gac 20g in step (2) gained solution, 20 ℃ of temperature controls, stirred after 30 minutes, filters carbon removal, filtrate for later use;
(4) desalting purifying: step (3) gained filtrate is carried out to nanofiltration desalination, and when the μ s/cm of nanofiltration liquid specific conductivity≤650, nanofiltration completes, and gained feed liquid is standby;
(5) resin purification: step (4) gained feed liquid is crossed to macroporous resin, and flow velocity 1.0BV/h, when the μ s/cm of feed liquid specific conductivity≤120, completes separation, and gained feed liquid is standby;
(6) spraying is dry: step (5) gained feed liquid is imported in spray-drier, and temperature is controlled at 5 ℃, obtains white amorphous powder hydroxypropyl-beta-cyclodextrin.
Table 2 embodiment 1 and comparative example 8 product analysis results
| ? | 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 changes and conversion.Within the spirit and principles in the present invention all, any modification of doing, be equal to replacement, improvement etc., within all should being included in protection scope of the present invention.
Claims (6)
1. a preparation method for hydroxypropyl-beta-cyclodextrin, is characterized in that step comprises:
(1) starch milk that is 12%-14% by distilled water modulation starch quality concentration stirs 30-50 minute at 75-85 ℃; Again temperature is adjusted to 40-45 ℃, the concentration that adds 9-13 Ge Meihuo unit according to every gram of starch adds cyclomaltodextrin glucanotransferase, add again organic solvent: addition is that every gram of starch adds after the hexanaphthene of 0.8-1.1mL, conversion reaction 6-7 hour, in conversion process, regulate pH value 8-9, after filtering, filtrate adopts the means of crystallization to obtain beta-cyclodextrin product;
(2) by mass concentration, be that 20%～25% aqueous sodium hydroxide solution is heated to 50-55 ℃, the beta-cyclodextrin that slowly adds while stirring step (1) to obtain, continue to stir until beta-cyclodextrin dissolves completely, cool to room temperature, under water-bath, in 3h-3.5h, evenly drip 1 while stirring, 2-propylene oxide 30-35ml, dropping process is controlled at 22～24 ℃ by temperature, 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) reactant step (2) being obtained neutralizes with hydrochloric acid, regulates and makes its pH=7;
(4) reaction solution step (3) being obtained carries out underpressure distillation, and the soup compound dissolve with ethanol obtaining stirs, and filters, then carries out underpressure distillation and obtain underflow;
(5) step (4) gained underflow is imported in spray-drier, temperature is controlled at 5～10 ℃, obtains white amorphous powder hydroxypropyl-beta-cyclodextrin.
2. method according to claim 1, is characterized in that the starch in step (1) is yam starch.
3. method according to claim 1, is characterized in that in step (1), organic solvent is hexanaphthene.
4. method according to claim 1, it is characterized in that in step (1) that the concentration that every gram of starch adds 10-12 Ge Meihuo unit adds cyclomaltodextrin glucanotransferase, the concentration that preferably every gram of starch adds 11Ge Meihuo unit adds cyclomaltodextrin glucanotransferase.
5. according to the method one of claim 1-4 Suo Shu, it is characterized in that in step (2), aqueous sodium hydroxide solution mass concentration is 21%～24%; Preferred mass concentration is 23%.
6. according to the method one of claim 1-4 Suo Shu, it 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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| CN111808299A (en) * | 2020-07-02 | 2020-10-23 | 山东滨州智源生物科技有限公司 | Preparation method of hydroxypropyl betacyclodextrin aqueous solution |
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| CN111820219A (en) * | 2020-07-29 | 2020-10-27 | 山东滨州智源生物科技有限公司 | Application of hydroxypropyl-beta-cyclodextrin in preparation of antibacterial material, food package and preparation method of food package |
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