CN106421809B - A kind of preparation method and product of pomegranate ellagic acid inclusion compound - Google Patents
A kind of preparation method and product of pomegranate ellagic acid inclusion compound Download PDFInfo
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Abstract
The invention discloses a kind of preparation methods of pomegranate ellagic acid inclusion compound, include the following steps：Pomegranate ellagic acid ethanol solution is added dropwise into hydroxypropyl beta cyclodextrin aqueous solution, is ultrasonically treated, obtains reaction solution；The reaction solution is shaken and is stirred, is included, obtains inclusion mother liquor；After the inclusion mother liquor is concentrated, is freeze-dried, the pomegranate ellagic acid inclusion compound is obtained.The present invention is using hydroxypropyl beta cyclodextrin as inclusion agents, pomegranate ellagic acid is included in a manner that supersound process, concussion stirring and freeze-drying combine, and coordinating rational process conditions, not only inclusion rate is high but also yield, dissolubility and stability are very high for the pomegranate ellagic acid inclusion compound of acquisition.
Description
Technical field
The present invention relates to the preparation methods and production of inclusion compound preparation field more particularly to a kind of pomegranate ellagic acid inclusion compound
Product.
Background technology
Polyphenol compound refers to the general designation of chemical element in one group of plant, gains the name when being rolled into a ball with multiple phenolic group, according to
According to polyphenol type, two classes can be divided into：
One kind is polyphenol monomer, i.e. non-polymer, including various flavone compounds (flavones, isoflavones, flavonols, Huang
Alkanone, flavanols, flavanonol, anthocyanin, chalcone etc.), chlorogenic acid, gallic acid and ellagic acid, also including some
It is connected to glycosyl complex class polyphenolic substance (such as rutin sophorin)；The common isoflavones of daily life, Bulbus Allii Cepae extract, green tea
Extract, blueberry extract etc. belong to this one kind.
It is another kind of, it is the oligomeric or polymer formed by monomer polymerization, is referred to as tannin, including condensed type tannin
Nutgall tannin and Ellagitannins etc. in Procyanidins and hydrolysis-type tannin；The common oolong tea extract of daily life, grape
Seed extract, green apple extract, youngster's tea tree extract etc. belong to this one kind.
Pomegranate ellagic acid is a kind of naturally occurring polyphenol compound in pomegranate, has anti-oxidant, antitumor, anti-inflammatory, anti-
The multiple pharmacological effects such as bacterium, skin brightening.However, pomegranate ellagic acid is almost insoluble in water, to photo-labile, body absorption
It is low, affect the clinical practice of pomegranate ellagic acid.
Inclusion technique is to utilize to include the larger hole of material host molecule by the embedding formation molecular glue of enclosed molecule insoluble drug packet
The technology of capsule inclusion compound can improve insoluble drug solubility and stability.Wherein, hydroxypropyl-β-cyclodextrin
(hydroxypropyl- β-cyclodextrin, HP- β-CD) is one of common inclusion material, itself is nontoxic, is had preferable
Water-soluble and thermal stability after forming inclusion compound with insoluble drug, on the one hand can increase the solubility of drug, on the other hand also
The bioavilability and stability of drug can be improved.
At present, have and drug solubility and biological stability are largely improved using inclusion technique about polyphenol compound
Document report, such as：
(1) Li Shoujun etc. studies the preparation process of procyanidine hydroxypropyl-beta-cyclodextrin inclusion, it is determined that most
Good preparation process feeds intake the mass ratio (mass ratio 1 of procyanidine and hydroxypropyl-β-cyclodextrin:4), hydroxypropyl-β-cyclodextrin matter
Measure score 30%, inclusion 20 DEG C of temperature, inclusion time 2.5h, obtain using solution stirring method to procyanidine carry out inclusion be can
Capable, and conclusion (the procyanidine hydroxypropyl-beta-cyclodextrin inclusions such as Li Shoujun, Liu Li, Fang Dan that inclusion rate is 24.5%
04 phases of research Heilungkiang medical science .2016 of preparation process).
(2) Chen Shuai etc. is using inclusion rate and the overall desirability of yield as inspection target, using differential scanning calorimetry to packet
The formation for closing object is verified, finds beta-cyclodextrin and resveratrol rate of charge (molar ratio) 2: 1,40 DEG C of temperature of inclusion, inclusion
During time 63min, differential scanning calorimetry analysis result shows that resveratrol Benexate Hydrochloride has been formed.Inclusion rate is
44.58% (the preparation process food of the such as Chen Shuai, Wang Huizhu, Zhong Fangli response phase methods optimization resveratrol beta cyclodextrin clathrate
09 phases of industrial technology .2015).
(3) Ou Yangyuzhu etc. is prepared for tea polyphenols-beta-cyclodextrin inclusion complex, uses infrared spectrum using beta-cyclodextrin as wall material
Envelope product is characterized with ultraviolet spectra.Inclusion complex is examined to Ultrasonic Radiation, oxidant and Pb2+The stabilization of effect
Property.The experimental results showed that respectively with 80 DEG C of ultrasonic radiations and room temperature 0.08mol/L Pb2+Aoxidize 360min, the Δ A/ of tea polyphenols
A0Value is bigger than inclusion complex by 48.54% and 45.28%；At a temperature of room temperature and 80 DEG C, with 0.1mol/L KClO3Solution oxide
360min, the Δ A/A of tea polyphenols0Distinguish big by the 33.6% and 73.41% (such as Ou Yangyuzhu, stone Aiwa, Chen little Dong than inclusion complex
Tea polyphenols -08 phases of beta-cyclodextrin inclusion complex Study of Antioxidation food and fermentation industries .2007).
(4) horse narcissus etc. prepares hesperetin/cyclodextrin coordination inclusion compound, wherein hesperetin and cyclodextrin and its
Derivative is 3 in molar ratio:1 ratio accurately weighs, and hesperetin compound (0.03mM, 9.1mg) is first dissolved in ethanol/water
Mixed solution in, the volume ratio of ethyl alcohol and water is 1:4, half an hour is stirred at room temperature, adds in the cyclodextrin weighed up and its spreads out
Biology (0.01mM：β-CD-11.35mg；DMβ-CD-13.3mg；TMβ-CD-14.3mg；HP β-CD-14.6mg), at room temperature after
Continuous stirring 7 days.Responseless substrate is filtered after 7 days, then filtrate is evaporated to obtain containing part by Rotary Evaporators
The inclusion compound of solvent by drying 12 hours in 50 DEG C of vacuum drying chambers, obtains hesperetin/cyclodextrin coordination inclusion compound.
Hesperetin/ β-CD, Hesperetin/DM β-CD, Hesperetin/TM β-CD, Hesperetin/HP β-CD yields difference
For 86%, 88%, 92% and 89% (the inclusion behavior of tri- kinds of natural flavones of horse narcissus and cyclodextrin and the property research Yunnan people
University of race Master's thesis .2012 Mays).
(5) Vipin D.Bulani etc. obtain ellagic acid hydroxypropyl-beta-cyclodextrin inclusion (EA- by freeze-drying
HP- β-CD), and to its inclusion compound using infra-red sepectrometry (FTIR), XRD (X-ray diffraction method), scanning electron microscope (SEM), nuclear-magnetism
Resonance (NMR) and molecular model method are verified.Research finds that ellagic acid and hydroxypropyl-β-cyclodextrin molecular proportion are 1:When 2,
Compared with simple ellagic acid, inclusion compound dissolution in vitro rate in phosphate buffer (pH 6.8) can increase by 500, i.e., from 55%
Rise to 60%.(Vipin D.Bulani,Pankaj S.Kothavade,Dnyaneshwar M.Nagmoti,et
al.Characterisation and anti-inflammatory evaluation of the inclusion complex
of ellagic acid with hydroxylpropyl-b-cyclodextrin.J Incl Phenom Macrocycl
03 phases of Chem.2015).
Although as can be seen that, have grinding for a large amount of published polyphenol compound inclusion compounds at present from above-mentioned document
Study carefully, but the research for ellagic acid inclusion compound is also less, and the studies above generally existing inclusion rate is low, solubility needs to be carried
The problems such as high.Therefore, it is necessary to inclusion technique is further probed into improve the inclusion rate of ellagic acid inclusion compound, yield, solubility
And stability.
Invention content
The present invention provides a kind of preparation method and product of ellagic acid inclusion compound, the ellagic acid packet that this method prepares
Composition powder inclusion rate, yield, solubility and stability are significantly increased.
A kind of preparation method of pomegranate ellagic acid inclusion compound, includes the following steps：
(1) pomegranate ellagic acid ethanol solution is added dropwise into hydroxypropyl-β-cyclodextrin aqueous solution, is ultrasonically treated,
Obtain reaction solution；
(2) reaction solution is shaken and stirred, included, obtain inclusion mother liquor；
(3) after the inclusion mother liquor being concentrated, is freeze-dried, the pomegranate ellagic acid inclusion compound is obtained.
The host molecule of this inclusion compound is hydroxypropyl-β-cyclodextrin, and enclosed molecule is pomegranate ellagic acid, utilizes the sky between host molecule
It wraps the effects that embedding effect and host and guest's intermolecular Van der Waals force power and forms container molecule in cave.
Hydroxypropyl-β-cyclodextrin and the amount ratio of pomegranate ellagic acid generate shadow to the forming amount and its stability of inclusion compound
It rings.Preferably, in step (1), the molar ratio of the hydroxypropyl-β-cyclodextrin and pomegranate ellagic acid is 3~1:1；It is further preferred that
Hydroxypropyl-β-cyclodextrin and the molar ratio of pomegranate ellagic acid are 2:1.
Preferably, in the pomegranate ellagic acid ethanol solution, the amount ratio of pomegranate ellagic acid and ethanol solution is
0.302g:100~150ml.If pomegranate ellagic acid content is higher, pomegranate ellagic acid insoluble matter is excessive；Conversely, then cause pomegranate
Ellagic acid concentration is inadequate.
Preferably, in step (1), the temperature of the ultrasound is 10~30 DEG C, and frequency is 100~500kHz, and the time is
10~30min.If temperature is too high, frequency is too big, overlong time, pomegranate ellagic acid stability can be produced bigger effect；Instead
It, the dissolving of pomegranate ellagic acid is very little.
Preferably, in step (2), the frequency of the concussion stirring is 80~150rpm.If frequency is excessive or too small, no
Conducive to being uniformly mixed, the formation of inclusion can be influenced.
Preferably, in step (2), the temperature of the concussion stirring is 20~40 DEG C, the time for 12~for 24 hours.If temperature
Excessively high, overlong time can then destroy the structure of pomegranate ellagic acid；Conversely, it is unfavorable for the formation of inclusion.
Preferably, in step (3), the inclusion mother liquor concentrations to mass concentration are 75~85%.If concentrate concentration mistake
Height then easily causes mother liquor drug and glues wall；Conversely, moisture is too many.
Preferably, in step (3), the temperature of the freeze-drying is -60~-20 DEG C, and the time is 48~72h.
Compared with prior art, the invention has the advantages that：
The present invention stirs and is freeze-dried what is combined using hydroxypropyl-β-cyclodextrin as inclusion agents, using being ultrasonically treated, shaking
Mode includes pomegranate ellagic acid, and coordinates rational process conditions, and the pomegranate ellagic acid inclusion compound of acquisition not only includes
Rate is high and yield, dissolubility and stability are very high.
Specific embodiment
The present invention is further described through with reference to specific implementation case；Wherein, the following example is related in following
Hold：
(1) material and reagent：Ellagic acid standard items are purchased from Tianjin spike biotech development Co., Ltd, HP- β-CD purchases
From Shanghai Bai Ao bio tech ltd.
(2) chromatographic condition used for：Chromatographic column：Hypersil C18 (250mm × 4.6mm, 5 μm)；Mobile phase：Second
Nitrile：0.3%TFA (20:80)；30 DEG C of column temperature；Flow velocity 1.0mL/min；10 μ L of sample size；Detection wavelength 254nm.In above-mentioned chromatography
Under the conditions of, the peak type of ellagic acid characteristic peak is good.
(3) preparation method of EA reference substance solutions is：Accurately weighed ellagic acid reference substance 10.48mg, is placed in 100ml capacity
In bottle, dissolved with methanol and be settled to scale, the reference substance storing solution of a concentration of 0.1048mg/ml is made.
(4) preparation method of EA-HP- β-CD test solutions is：It takes EA-HP- β-CD appropriate, is placed in the measuring bottle of 10ml
In, methanol, ultrasonic 30min are added in, and with methanol dilution to scale, shake up, with 0.45 μm of filtering with microporous membrane, take subsequent filtrate
To obtain the final product.
(5) method for drafting of standard curve is：Precision absorption ellagic acid reference substance solution is appropriate, after dilution, obtains a concentration of
0.1048th, the series standard solution of 0.524,1.048,2.096,5.240,10.48,20.96 μ g/ml, according to color described above
Spectral condition injects high performance liquid chromatograph, records chromatogram, using peak area as abscissa (X), series standard solution concentration is vertical
Coordinate (Y), draws the standard curve of ellagic acid, and the regression equation of ellagic acid is：Y=0.6285X+0.0468, r=0.9999 (n
=7), the range of linearity is 0.1048~20.96 μ g/ml.
(6) method of sample recovery rate experiment is：EA-HP- β-the CD of known quality concentration (1.048 μ g/ml) are taken for examination
Product solution 10ml, is separately added into appropriate ellagic acid reference substance solution, as stated above according to basic, normal, high three concentration by totally 9 parts
Prepare ellagic acid reference substance solution；And sample introduction is analyzed, the average recovery rate for calculating ellagic acid is 99.55%, RSD 1.44%.
(7) calculating of inclusion rate：The pomegranate ellagic acid inclusion compound prepared is placed in 10mL measuring bottles, methanol is added to fit
Amount, ultrasonic 30min, again with methanol are diluted to scale, shake up.Chromatographic condition as described above is analyzed, according to external standard method
The content of EA is calculated, following formula is substituted into and calculates inclusion rate.
Medication amount/input medication amount × 100 in inclusion rate/%=inclusion compounds；
The quality of inclusion compound yield (%)=inclusion compound/(hydroxypropyl-β-cyclodextrin quality+medicine feeding quality) × 100.
(8) assay method of inclusion compound solubility is：Excessive PA and PA inclusion compounds are taken, are respectively placed in 10ml tool plug scale examinations
Guan Zhong adds appropriate amount of water, at room temperature shake well, is allowed to dissolving up to balance, is then centrifuged for, supernatant is taken to be filtered with 0.45 μm of micropore
Membrane filtration mistake, subsequent filtrate, with water dilute suitable multiple after, in 254nm at measure absorption value, according to calibration curve equation calculate PA with
The solubility of PA inclusion compounds.
(9) measure of stability：Most of polyphenols have characteristic ultraviolet absorption spectrum, wherein, pomegranate ellagic acid
There is significant absorption peak in 254nm, when the structure of pomegranate ellagic acid changes, corresponding feature ultraviolet absorption band also one
Surely it changes, therefore can the variation of its structure can be speculated by the variation of peak shape and peak position.
Pomegranate ellagic acid and pomegranate ellagic acid inclusion compound stability are compared by temperature, pH value and metal ion,
Specific method is as follows：
(a) 0.302g pomegranate ellagic acid inclusion compounds are taken, is dissolved in the water of 100mL, is configured to a concentration of 0.01mol/L's
Solution.
(b) sample, be heated to 80 DEG C, the time respectively 0,5,10,20,30,35,40,60,100,250,400,600min
After sample 800 μ L constant volumes in 10mL carry out ultraviolet determination, scanning range be 200~800nm, compare its spectrogram variation.
(c) several pieces are sampled, then adjust different pH value (1-14), sampling 2mL constant volumes are in the volumetric flask of 10mL after 72h
In, uv scan is carried out, scanning range is 200~800nm,.
(d) it samples, adds in 0.1mol/L metal ion solutions (such as Fe3+), UV, visible light is carried out to it after being uniformly mixed 6h
Spectral scan, 200~800nm of wavelength scanning range.
" EA " referred in the following example represents ellagic acid, and " PA " represents pomegranate ellagic acid.
Embodiment 1
A kind of pomegranate ellagic acid inclusion compound, preparation method are as follows：
(1) 2.862g hydroxypropyl-β-cyclodextrins is taken to be dissolved in 20ml water, obtain hydroxypropyl-β-cyclodextrin aqueous solution；It takes
0.302g pomegranate ellagic acids are dissolved in the ethyl alcohol of 100ml, and it is molten that pomegranate ellagic acid ethyl alcohol is obtained by filtration in miillpore filter (0.45 μm)
Liquid；The hydroxypropyl-β-cyclodextrin aqueous solution of 20ml is ultrasonically treated, and while ultrasound, to hydroxypropyl-β-cyclodextrin
It is slowly added to the pomegranate ellagic acid ethanol solution of 80ml in aqueous solution dropwise, 25 DEG C, under 300kHz frequencies after ultrasound 30min, obtain
To reaction solution；
(2) reaction solution obtained in step (1) under 30 DEG C, 100rpm frequencies is shaken into stirring 18h, carries out pomegranate tan flower
Acid and the inclusion of hydroxypropyl-β-cyclodextrin obtain inclusion mother liquor；
(3) by it is described inclusion mother liquor concentrations to 10ml (wherein, a concentration of 80% or so) of pomegranate ellagic acid inclusion compound, then
48h is freeze-dried at -40 DEG C, obtains the pomegranate ellagic acid inclusion compound.
Embodiment 2
A kind of pomegranate ellagic acid inclusion compound, preparation method are as follows：
(1) 2.862g hydroxypropyl-β-cyclodextrins is taken to be dissolved in 20ml water, obtain hydroxypropyl-β-cyclodextrin aqueous solution；It takes
0.302g pomegranate ellagic acids are dissolved in the ethyl alcohol of 100ml, and it is molten that pomegranate ellagic acid ethyl alcohol is obtained by filtration in miillpore filter (0.45 μm)
Liquid；The hydroxypropyl-β-cyclodextrin aqueous solution of 20ml is ultrasonically treated, and while ultrasound, to hydroxypropyl-β-cyclodextrin
It is slowly added to the pomegranate ellagic acid ethanol solution of 80ml in aqueous solution dropwise, 25 DEG C, under 200kHz frequencies after ultrasound 30min, obtain
To reaction solution；
(2) reaction solution obtained in step (1) under 30 DEG C, 120rpm frequencies is shaken into stirring 18h, carries out pomegranate tan flower
Acid and the inclusion of hydroxypropyl-β-cyclodextrin obtain inclusion mother liquor；
(3) by it is described inclusion mother liquor concentrations to 10ml (wherein, a concentration of 75% or so) of pomegranate ellagic acid inclusion compound, then
48h is freeze-dried at -40 DEG C, obtains the pomegranate ellagic acid inclusion compound.
Embodiment 3
A kind of pomegranate ellagic acid inclusion compound, preparation method are as follows：
(1) 2.862g hydroxypropyl-β-cyclodextrins is taken to be dissolved in 20ml water, obtain hydroxypropyl-β-cyclodextrin aqueous solution；It takes
0.302g pomegranate ellagic acids are dissolved in the ethyl alcohol of 100ml, and it is molten that pomegranate ellagic acid ethyl alcohol is obtained by filtration in miillpore filter (0.45 μm)
Liquid；The hydroxypropyl-β-cyclodextrin aqueous solution of 20ml is ultrasonically treated, and while ultrasound, to hydroxypropyl-β-cyclodextrin
It is slowly added to the pomegranate ellagic acid ethanol solution of 80ml in aqueous solution dropwise, 25 DEG C, under 250kHz frequencies after ultrasound 30min, obtain
To reaction solution；
(2) reaction solution obtained in step (1) under 30 DEG C, 130rpm frequencies is shaken into stirring 18h, carries out pomegranate tan flower
Acid and the inclusion of hydroxypropyl-β-cyclodextrin obtain inclusion mother liquor；
(3) by it is described inclusion mother liquor concentrations to 10ml (wherein, a concentration of 85% or so) of pomegranate ellagic acid inclusion compound, then
48h is freeze-dried at -20 DEG C, obtains the pomegranate ellagic acid inclusion compound.
Embodiment 4
A kind of pomegranate ellagic acid inclusion compound, preparation method are as follows：
(1) 2.862g hydroxypropyl-β-cyclodextrins is taken to be dissolved in 20ml water, obtain hydroxypropyl-β-cyclodextrin aqueous solution；It takes
0.302g pomegranate ellagic acids are dissolved in the ethyl alcohol of 100ml, and it is molten that pomegranate ellagic acid ethyl alcohol is obtained by filtration in miillpore filter (0.45 μm)
Liquid；The hydroxypropyl-β-cyclodextrin aqueous solution of 20ml is ultrasonically treated, and while ultrasound, to hydroxypropyl-β-cyclodextrin
It is slowly added to the pomegranate ellagic acid ethanol solution of 80ml in aqueous solution dropwise, 25 DEG C, under 150kHz frequencies after ultrasound 30min, obtain
To reaction solution；
(2) reaction solution obtained in step (1) under 30 DEG C, 140rpm frequencies is shaken into stirring 18h, carries out pomegranate tan flower
Acid and the inclusion of hydroxypropyl-β-cyclodextrin obtain inclusion mother liquor；
(3) by it is described inclusion mother liquor concentrations to 10ml (wherein, a concentration of 75% or so) of pomegranate ellagic acid inclusion compound, then
48h is freeze-dried at -40 DEG C, obtains the pomegranate ellagic acid inclusion compound.
1 paddling process of comparative example
A kind of pomegranate ellagic acid inclusion compound, preparation method are as follows：
0.302g pomegranate ellagic acids is taken to be dissolved in the ethyl alcohol of 100ml, pomegranate tan is obtained by filtration in miillpore filter (0.45 μm)
Spend sour ethanol solution；2.862g hydroxypropyl-β-cyclodextrins is taken to be dissolved in 20ml water, obtain hydroxypropyl-β-cyclodextrin aqueous solution；It stirs
It mixes down, is slowly dropped into hydroxypropyl-β-cyclodextrin aqueous solution to pomegranate ellagic acid ethanol solution, stirs 1h at room temperature, overnight, take out
Filter, and wash inclusion compound with a small amount of absolute ethyl alcohol and precipitate, vacuum drying obtains pomegranate ellagic acid inclusion compound.
2 polishing of comparative example
A kind of pomegranate ellagic acid inclusion compound, preparation method are as follows：
0.302g pomegranate ellagic acids is taken to be dissolved in the ethyl alcohol of 100ml, pomegranate tan is obtained by filtration in miillpore filter (0.45 μm)
Spend sour ethanol solution；2.862g hydroxypropyl-β-cyclodextrins is taken to be dissolved in 20ml water, obtain hydroxypropyl-β-cyclodextrin aqueous solution；It will
Hydroxypropyl-β-cyclodextrin aqueous solution is ground into paste, then pomegranate ellagic acid is added in into the paste, is fully ground 1h, subtracts
Pressure filters, and filter cake obtains pomegranate ellagic acid inclusion compound in 50 DEG C of oven drieds to constant weight.
Comparative example 3 shakes stirring+freeze-drying
A kind of pomegranate ellagic acid inclusion compound, preparation method are as follows：
2.75g hydroxypropyl-β-cyclodextrins is taken to be dissolved in 20ml water, obtain hydroxypropyl-β-cyclodextrin aqueous solution；Take 0.302g
Ellagic acid is added in hydroxypropyl-β-cyclodextrin aqueous solution, obtains ellagic acid hydroxypropyl-β-cyclodextrin solution；It is shaken in room temperature
For 24 hours, (0.45 μm) filtering of miillpore filter, filtrate is freeze-dried for 24 hours at -60 DEG C, obtains pomegranate ellagic acid inclusion compound for stirring.
4 ultrasounds of comparative example+stirring
A kind of pomegranate ellagic acid inclusion compound, preparation method are as follows：
2.75g hydroxypropyl-β-cyclodextrins is taken to be dissolved in 20ml water, obtain hydroxypropyl-β-cyclodextrin aqueous solution；Take 0.302g
Ellagic acid is added in hydroxypropyl-β-cyclodextrin aqueous solution, obtains ellagic acid hydroxypropyl-β-cyclodextrin solution；At room temperature
Ultrasound stirs 1h, overnight, filters, and wash inclusion compound with a small amount of absolute ethyl alcohol and sink at room temperature to 30min under 300kHz frequencies
It forms sediment, vacuum drying obtains pomegranate ellagic acid inclusion compound.
Comparative example 5
A kind of pomegranate ellagic acid inclusion compound, preparation method are as follows：
(1) 2.862g hydroxypropyl-β-cyclodextrins is taken to be dissolved in 20ml water, obtain hydroxypropyl-β-cyclodextrin aqueous solution；It takes
0.302g pomegranate ellagic acids are dissolved in the ethyl alcohol of 100ml, and it is molten that pomegranate ellagic acid ethyl alcohol is obtained by filtration in miillpore filter (0.45 μm)
Liquid；The hydroxypropyl-β-cyclodextrin aqueous solution of 20ml is ultrasonically treated, and while ultrasound, to hydroxypropyl-β-cyclodextrin
It is slowly added to the pomegranate ellagic acid ethanol solution of 80ml in aqueous solution dropwise, 25 DEG C, under 50kHz frequencies after ultrasound 40min, obtain
Reaction solution；
(2) reaction solution obtained in step (1) under 30 DEG C, 200rpm frequencies is shaken into stirring 12h, carries out pomegranate tan flower
Acid and the inclusion of hydroxypropyl-β-cyclodextrin obtain inclusion mother liquor；
(3) by it is described inclusion mother liquor concentrations to 10ml (wherein, a concentration of 80% or so) of pomegranate ellagic acid inclusion compound, then
48h is freeze-dried at -40 DEG C, obtains the pomegranate ellagic acid inclusion compound.
Comparative example 6
A kind of pomegranate ellagic acid inclusion compound, preparation method are as follows：
(1) 2.862g hydroxypropyl-β-cyclodextrins is taken to be dissolved in 20ml water, obtain hydroxypropyl-β-cyclodextrin aqueous solution；It takes
0.302g pomegranate ellagic acids are dissolved in the ethyl alcohol of 100ml, and it is molten that pomegranate ellagic acid ethyl alcohol is obtained by filtration in miillpore filter (0.45 μm)
Liquid；The hydroxypropyl-β-cyclodextrin aqueous solution of 20ml is ultrasonically treated, and while ultrasound, to hydroxypropyl-β-cyclodextrin
It is slowly added to the pomegranate ellagic acid ethanol solution of 80ml in aqueous solution dropwise, 25 DEG C, under 600kHz frequencies after ultrasound 20min, obtain
To reaction solution；
(2) reaction solution obtained in step (1) under 30 DEG C, 60rpm frequencies is shaken into stirring 30h, carries out pomegranate tan flower
Acid and the inclusion of hydroxypropyl-β-cyclodextrin obtain inclusion mother liquor；
(3) by it is described inclusion mother liquor concentrations to 10ml (wherein, a concentration of 80% or so) of pomegranate ellagic acid inclusion compound, then
48h is freeze-dried at -40 DEG C, obtains the pomegranate ellagic acid inclusion compound.
Comparative example 7
A kind of pomegranate ellagic acid inclusion compound, preparation method are as follows：
(1) 2.862g hydroxypropyl-β-cyclodextrins is taken to be dissolved in 20ml water, obtain hydroxypropyl-β-cyclodextrin aqueous solution；It takes
0.302g pomegranate ellagic acids are dissolved in the ethyl alcohol of 100ml, and it is molten that pomegranate ellagic acid ethyl alcohol is obtained by filtration in miillpore filter (0.45 μm)
Liquid；The hydroxypropyl-β-cyclodextrin aqueous solution of 20ml is ultrasonically treated, and while ultrasound, to hydroxypropyl-β-cyclodextrin
It is slowly added to the pomegranate ellagic acid ethanol solution of 80ml in aqueous solution dropwise, 25 DEG C, under 300kHz frequencies after ultrasound 30min, obtain
To reaction solution；
(2) by the reaction solution obtained in step (1) in 30 DEG C, stirring 18h, progress pomegranate ellagic acid and hydroxy propyl-Beta-ring
The inclusion of dextrin obtains inclusion mother liquor；
(3) by it is described inclusion mother liquor concentrations to 10ml (wherein, a concentration of 80% or so) of pomegranate ellagic acid inclusion compound, then
48h is freeze-dried at -40 DEG C, obtains the pomegranate ellagic acid inclusion compound.
Inclusion rate, yield, solubility and steady are carried out to the pomegranate ellagic acid inclusion compound that above-described embodiment and comparative example obtain
It qualitatively measures, the results are shown in Table 1 for acquisition.
Inclusion rate, yield, solubility and the stability for the pomegranate ellagic acid inclusion compound that 1 Different Preparation of table obtains
From the above results, inclusion rate, yield, solubility and steady can be obtained using the preparation method of Examples 1 to 4
Qualitative higher pomegranate ellagic acid inclusion compound, wherein, the preparation method of embodiment 1 is best.
As can be seen that being combined using supersound process, concussion stirring and freeze-drying from the comparison of embodiment and comparative example
Mode inclusion processing is carried out to pomegranate ellagic acid, best result can be obtained；And it individually uses at one of which or two kinds
Reason method can not obtain optimum, and the result that individually one or two kinds of processing methods obtain is irregular follows, can not
It is expected that.
Claims (3)
1. a kind of preparation method of pomegranate ellagic acid inclusion compound, which is characterized in that include the following steps：
(1) pomegranate ellagic acid ethanol solution is added dropwise into hydroxypropyl-β-cyclodextrin aqueous solution, is ultrasonically treated, obtains
Reaction solution；The hydroxypropyl-β-cyclodextrin and the molar ratio of pomegranate ellagic acid are 3~1:1；The temperature of the ultrasound is 10~30
DEG C, frequency is 100~500kHz, and the time is 10~30min；
(2) reaction solution is shaken and stirred, included, obtain inclusion mother liquor；The frequency of the concussion stirring for 80~
150rpm；The temperature of the concussion stirring for 20~40 DEG C, the time for 12~for 24 hours；
(3) after the inclusion mother liquor being concentrated, is freeze-dried, the pomegranate ellagic acid inclusion compound is obtained；The freezing is dry
Dry temperature is -60~-20 DEG C, and the time is 48~72h.
2. preparation method as described in claim 1, which is characterized in that in the pomegranate ellagic acid ethanol solution, pomegranate tan flower
The amount ratio of acid and ethanol solution is 0.302g:100~150ml.
3. preparation method as described in claim 1, which is characterized in that in step (3), the inclusion mother liquor concentrations are dense to quality
Spend is 75~85%.
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