CN102633911B - Method for preparing hydroxypropyl-beta-cyclodextrin by catalysis of starch microsphere supported calcium hydroxides - Google Patents
Method for preparing hydroxypropyl-beta-cyclodextrin by catalysis of starch microsphere supported calcium hydroxides Download PDFInfo
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Abstract
The invention discloses a method for preparing hydroxypropyl-beta-cyclodextrin by catalysis of starch microsphere supported calcium hydroxide. The method comprises the following steps of: adding beta-cyclodextrin, propylene oxide, a catalyst and water serving as a reaction solvent into reaction equipment, and reacting under certain pressure condition, wherein the reaction temperature is controlled to effectively improve the yield and the purity of the product; quickly drying the reaction product by using a spray dryer to obtain the finished product hydroxypropyl-beta-cyclodextrin. The product has the advantages of low water content, uniform particle size distribution, high whiteness, moderate substitution degree, moderate fleeciness feeling and the like, the purity of the product reaches over 99 percent, and the total yield of the reaction is over 95 percent.
Description
Technical field
The present invention relates to a kind of preparation method of hydroxypropyl-beta-cyclodextrin, particularly the catalysis of a kind of spherex loaded calcium hydroxide prepares the method for hydroxypropyl-beta-cyclodextrin.
Background technology
Beta-cyclodextrin consists of 7 glucose units, the 2-of each glucosyl residue, and 3-, the hydrogen atom in the hydroxyl of 6-position can be replaced by hydroxypropyl, obtains hydroxypropyl-beta-cyclodextrin.Hydroxypropyl-beta-cyclodextrin mainly is applied as the auxiliary material medicine at field of medicaments, and principal feature is: 1. increase the water-soluble of insoluble drug; 2. increase medicine stability, improve drug bioavailability; 3. reduce the toxic side effect of medicine.Hydroxypropyl-beta-cyclodextrin can be used for the carrier of oral pharmaceutical, injection, mucoadhesive delivery system, Transdermal absorption drug delivery system, lipotropy targeted drug, also can be used as protective material and the stablizer of protein.
Spherex is as a kind of derivative of natural polymer product starch, has an Environmental compatibility good, the characteristics to human body without any toxic action, and its vesicular structure makes it become a kind of support of the catalyst of excellent property.
Summary of the invention
The object of the present invention is to provide the catalysis of a kind of spherex loaded calcium hydroxide to prepare the method for hydroxypropyl-beta-cyclodextrin, can overcome the unmanageable shortcoming of alkaline catalysts in traditional hydroxypropyl-beta-cyclodextrin production process, but not affecting purity and the yield of product, is the production method of the hydroxypropyl-beta-cyclodextrin that a kind of technique is simple, cost is low.
For achieving the above object, the technical solution used in the present invention is:
1) at first, add 100L deionized water and 100-160g calcium hydroxide in conversion unit, stir 0.5-2 hour, add again 2-4kg porous-starch microballoon, the control stirring velocity is 100-300r/min, and stirring reaction 1-5 hour under room temperature condition filters, filter cake is used deionized water drip washing 3 times, obtains porous-starch micro-ball load calcium hydroxide catalyzer;
2) secondly, add the catalyzer of beta-cyclodextrin, beta-cyclodextrin quality 3%-8% in conversion unit, and by beta-cyclodextrin: the mass ratio of water=1: 5-10 adds reaction solvent water, stirs and obtains mixing solutions;
3) then, at 15-25 ℃, to the pressure that is filled with 0.5Mpa-5Mpa in mixing solutions, the control temperature of reaction system is 15-25 ℃, and according to the mol ratio beta-cyclodextrin: propylene oxide=1: 3-7 drips propylene oxide, controls rate of addition, within 5-10 hour, dropwises;
4) last, keep reaction 12-36 hour in 15-25 ℃, after react, filter to isolate spherex, after gained liquid is regulated to its solid content and is 5%-10%, the use spray-dryer dusts, and obtains the product hydroxypropyl-beta-cyclodextrin.
The present invention adopts absorption method to prepare porous-starch micro-ball load calcium hydroxide catalyzer, in the aqueous solution of calcium hydroxide, adds the porous-starch microballoon, makes calcium hydroxide be adsorbed in the inside of spherex, and then reaches the requirement of load.Adopt spherex loaded calcium hydroxide catalyzer to prepare hydroxypropyl-beta-cyclodextrin, and consider and apply and must be reacted by pressure, can effectively improve yield and the purity of product, the finished product are used spray-dryer rapid drying to obtain.Product has the advantages such as water-content is low, particle size distribution is even, whiteness is high, substitution value is suitable, fluffy sense appropriateness, the production method that this is a kind of green, technique is simple, yield is high, purity is high, cost is low.
Embodiment
Embodiment 1:
1) at first, add 100L deionized water and 100g calcium hydroxide in conversion unit, stir 0.5 hour, add again 4kg porous-starch microballoon, the control stirring velocity is 300r/min, and under room temperature condition, stirring reaction is 3 hours, filters, filter cake is used deionized water drip washing 3 times, obtains porous-starch micro-ball load calcium hydroxide catalyzer;
2) secondly, add the catalyzer of beta-cyclodextrin, beta-cyclodextrin quality 5% in conversion unit, and by beta-cyclodextrin: the mass ratio of water=1: 8 adds reaction solvent water, stirs and obtains mixing solutions;
3) then, at 25 ℃, to the pressure that is filled with 3Mpa in mixing solutions, controlling temperature of reaction system is 25 ℃, according to the mol ratio beta-cyclodextrin: propylene oxide=drip propylene oxide at 1: 7, control rate of addition, within 5 hours, dropwise;
4) last, keep reaction 36 hours in 25 ℃, after react, filter to isolate spherex, after gained liquid is regulated to its solid content and is 5%, the use spray-dryer dusts, and obtains the product hydroxypropyl-beta-cyclodextrin.Using high performance liquid chromatography to detect purity is 99%, yield 95%.
Embodiment 2:
1) at first, add 100L deionized water and 160g calcium hydroxide in conversion unit, stir 1 hour, add again 2kg porous-starch microballoon, the control stirring velocity is 100r/min, and under room temperature condition, stirring reaction is 1 hour, filters, filter cake is used deionized water drip washing 3 times, obtains porous-starch micro-ball load calcium hydroxide catalyzer;
2) secondly, add the catalyzer of beta-cyclodextrin, beta-cyclodextrin quality 3% in conversion unit, and by beta-cyclodextrin: the mass ratio of water=1: 10 adds reaction solvent water, stirs and obtains mixing solutions;
3) then, at 20 ℃, to the pressure that is filled with 0.5Mpa in mixing solutions, controlling temperature of reaction system is 20 ℃, according to the mol ratio beta-cyclodextrin: propylene oxide=drip propylene oxide at 1: 5, control rate of addition, within 8 hours, dropwise;
4) last, keep reaction 24 hours in 20 ℃, after react, filter to isolate spherex, after gained liquid is regulated to its solid content and is 8%, the use spray-dryer dusts, and obtains the product hydroxypropyl-beta-cyclodextrin.Using high performance liquid chromatography to detect purity is 99%, yield 96%.
Embodiment 3:
1) at first, add 100L deionized water and 140g calcium hydroxide in conversion unit, stir 2 hours, add again 3kg porous-starch microballoon, the control stirring velocity is 200r/min, and under room temperature condition, stirring reaction is 5 hours, filters, filter cake is used deionized water drip washing 3 times, obtains porous-starch micro-ball load calcium hydroxide catalyzer;
2) secondly, add the catalyzer of beta-cyclodextrin, beta-cyclodextrin quality 8% in conversion unit, and by beta-cyclodextrin: the mass ratio of water=1: 5 adds reaction solvent water, stirs and obtains mixing solutions;
3) then, at 15 ℃, to the pressure that is filled with 5Mpa in mixing solutions, controlling temperature of reaction system is 15 ℃, according to the mol ratio beta-cyclodextrin: propylene oxide=drip propylene oxide at 1: 3, control rate of addition, within 10 hours, dropwise;
4) last, keep reaction 12 hours in 15 ℃, after react, filter to isolate spherex, after gained liquid is regulated to its solid content and is 10%, the use spray-dryer dusts, and obtains the product hydroxypropyl-beta-cyclodextrin.Using high performance liquid chromatography to detect purity is 99%, yield 98%.
The present invention uses the spherex loaded calcium hydroxide as catalysts, in whole reaction process, catalyzer exists with the apparent form of spherex always, reaction is directly removed by the mode of solid-liquid separation after finishing, thereby saved traditional alkali lye as the needed ion-exchange unit of catalysts or iontophoretic injection equipment, and then simplified production technique.Product purity can reach more than 99%, and total recovery is more than 95%.
Claims (1)
1. spherex loaded calcium hydroxide catalysis prepares the method for hydroxypropyl-beta-cyclodextrin, it is characterized in that:
1) at first, add 100L deionized water and 100-160g calcium hydroxide in conversion unit, stir 0.5-2 hour, add again 2-4kg porous-starch microballoon, the control stirring velocity is 100-300r/min, and stirring reaction 1-5 hour under room temperature condition filters, filter cake is used deionized water drip washing 3 times, obtains porous-starch micro-ball load calcium hydroxide catalyzer;
2) secondly, add the catalyzer of beta-cyclodextrin, beta-cyclodextrin quality 3%-8% in conversion unit, and add reaction solvent water by the mass ratio of beta-cyclodextrin: water=1:5-10, stir and obtain mixing solutions;
3) then, at 15-25 ℃, to the pressure that is filled with 0.5MPa-5MPa in mixing solutions, the control temperature of reaction system is 15-25 ℃, and according to the mol ratio beta-cyclodextrin: propylene oxide=1:3-7 drips propylene oxide, controls rate of addition, within 5-10 hour, dropwises;
4) last, keep reaction 12-36 hour in 15-25 ℃, after react, filter to isolate spherex, after gained liquid is regulated to its solid content and is 5%-10%, the use spray-dryer dusts, and obtains the product hydroxypropyl-beta-cyclodextrin.
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| CN108034010A (en) * | 2017-12-29 | 2018-05-15 | 山东滨州智源生物科技有限公司 | A kind of environment-friendly preparation method thereof of hydroxypropyl cyclodextrin |
| CN111808299B (en) * | 2020-07-02 | 2022-05-31 | 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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