CN110423307A - A kind of preparation method and applications comprising alpha-cyclodextrin photo-thermal double stimuli responsive hydrogel - Google Patents
A kind of preparation method and applications comprising alpha-cyclodextrin photo-thermal double stimuli responsive hydrogel Download PDFInfo
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
- A61K41/0028—Disruption, e.g. by heat or ultrasounds, sonophysical or sonochemical activation, e.g. thermosensitive or heat-sensitive liposomes, disruption of calculi with a medicinal preparation and ultrasounds
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- A—HUMAN NECESSITIES
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- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
- A61K41/0042—Photocleavage of drugs in vivo, e.g. cleavage of photolabile linkers in vivo by UV radiation for releasing the pharmacologically-active agent from the administered agent; photothrombosis or photoocclusion
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- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/69—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
- A61K47/6949—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes
- A61K47/6951—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes using cyclodextrin
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Abstract
The invention belongs to technical field of environment function material preparation, are related to a kind of preparation method and applications comprising alpha-cyclodextrin photo-thermal double stimuli responsive hydrogel；Steps are as follows: preparing alpha-cyclodextrin ester and acrylamido azobenzene first, is then added in dimethyl sulfoxide solution together with methylene-bisacrylamide, N-isopropylacrylamide again, ultrasonic vibration obtains mixed liquid B；Then it takes azobisisoheptonitrile to be added in dimethyl sulfoxide solution, obtains mixed liquor D；Finally mixed liquor D is added in mixed liquid B, is reacted in water-bath after mixing, obtains photo-thermal double stimuli responsive hydrogel；Hydrogel prepared by the present invention introduces cyclodextrin and light, temperature configuration response unit simultaneously, can largely be loaded to drug molecule, and when ambient temperature and illumination wavelength change, and can adjust the responsiveness variation of drug molecule rate of release in time；Meanwhile operation of the present invention is easy, the hydrogel of preparation is safe and environment-friendly, stability is good.
Description
Technical field
The invention belongs to technical field of environment function material preparation, and in particular to one kind includes the dual thorn of alpha-cyclodextrin photo-thermal
Swash the preparation method and applications of response water gel.
Background technique
As the stable development and multi-disciplinary mutually deeply fusion, people of modern medical techniques are passed through with various
Material and method realize the further promotion to curative effect of medication, wherein realize more drug-rich, controllable rate of release
Exactly promote two important channels of curative effect of medication.Hydrogel is used as one of the ideal material of this drug controlled release.Water
Gel be it is a kind of be crosslinked by interactions such as covalent bond, hydrogen bond or Van der Waals forces made of with tridimensional network polymerization
Object can be swollen in water and keep large quantity of moisture and not dissolve, and have good biocompatibility and permeability, and according to reality
Border needs to synthesize different performance hydrogel material, ratio can also be crosslinked by increase hydrogel in synthesis process, to mention
It is risen as drug release carrier to improve mechanical strength and stability.Stimulation is introduced in structure in hydrogel polymer network
Responsiveness structural unit can be such that hydrogel realizes after by external environment variation stimulation by the variation of structure and performance
To the controllable adjustment of drug molecule rate of release and release mode.It is this spontaneous to environmental stimuli to make intelligence and stress ring
" intelligent aqueous gel " for answering behavior causes researcher because of the immense value that it shows in theoretical research and practical application
More and more interest and attention.According to the type classification of environmental stimuli, stimuli responsive macromolecular gel can be divided into thermal response,
The characteristics of pH response, photoresponse etc., different types of stimuli responsive system has its own, in certain specific environmental conditions
There is down respective advantage.But in recent years, light stimulus and thermal stimulus responsive polymer are because it is in safety, controllability and convenience
The unique advantage of property etc. causes researcher and more and more pays close attention to.Advantage using illumination and temperature as environmental stimuli
Be that it is all safe and nontoxic to environment and human body, non-contacting stimulation and control may be implemented, wherein illumination irradiation time,
Position and range, distance etc. can very easily be adjusted, and temperature can directly react people as important physiological parameter
The health status of body, thus it is possible to make the water of spontaneous response sexual behaviour according to the variation with human body temperature according to ambient light
Gel rubber material necessarily has important researching value in drug transportation aspect.
Existing literature research report, Inomata etc. have synthesized hydrogel with n-isopropyl acrylamide, these gels are in water
There is low temperature swelling, the temperature-responsive that high-temperature is shunk in solution.The researchs such as Chen Li find the water-setting containing azobenzene group
Glue has very sensitive responsiveness to ultraviolet light and pH, and gel volume obviously shrinks and becomes smaller after ultraviolet light；And with copolymerization
The rate of the increase of azobenzene group ratio in hydrogel, gel shrinks is accelerated.However it controls discharge in pharmaceutical hydrogel at present
Research in, mostly use single sensitive control system greatly, it is insufficient to drug molecule load capacity to result in hydrogel, the drug of load
The problem of molecule cannot effectively can be discharged into environment occurs.However the present invention is for the first time by azobenzene, cyclodextrin, N- isopropyl
Acrylamide carries out graft copolymerization, and photosensitive component and temperature sensitive component are collectively incorporated into hydrogel polymer network, increased greatly
Hydrogel has been added to improve the control releasing effect to drug molecule to the load capacity of drug molecule and further.
Summary of the invention
In view of the deficiencies of the prior art, present invention seek to address that one of described problem；The present invention provides a kind of for drug
The preparation method of the intelligent response hydrogel of controlled release；The hydrogel is logical when being changed by ambient temperature, illumination wavelength
The responsiveness variation of the compound/dissociation and temperature sensitive component shrink/expanded crossed between photosensitive compound system host-guest is realized pair
The controlled release of drug molecule, so as to the carrier material in terms of as intelligent transdermal drug delivery.
In order to achieve the goal above, the technical solution adopted by the present invention is that:
A kind of photo-thermal double stimuli responsive hydrogel comprising alpha-cyclodextrin, the hydrogel macromolecular chain is simultaneous with light
Sensing unit and temperature sensing unit.Photaesthesia monomer and temperature-sensitive monomeric are grafted to polymeric web by free radical polymerization
In network.Preparation step is as follows:
(1) preparation of alpha-cyclodextrin ester: alpha-cyclodextrin is carried out with dimethylformamide (DMF) under magnetic stirring molten
Solution, is then added dropwise triethylamine, and it is uniform to be placed in magnetic agitation in ice-water bath, under conditions of being passed through nitrogen protection, then is slowly added dropwise
Acryloyl chloride is reacted at room temperature after being added dropwise to complete, and is filtered by vacuum after reaction, removes and solid is precipitated, and collects filtrate
It is filtered again with after acetone precipitation, gained white solid is washed repeatedly with acetone filter again, and final product is dried in vacuo
To constant weight, alpha-cyclodextrin ester is obtained；
(2) by P-aminoazobenzene and benzene by dissolving under magnetic stirring, three the preparation of acrylamido azobenzene: are added
Ethamine is slowly added dropwise acryloyl chloride simultaneously in magnetic agitation, back flow reaction is then stirred under the conditions of certain temperature, is reacted
After be cooled to room temperature, after being filtered by vacuum, being dried Orange red solid, then be washed with distilled water, filter after be dried,
Then it is recrystallized with dehydrated alcohol, final product carries out being dried under vacuum to constant weight, obtains acrylamido azobenzene；
(3) preparation of photo-thermal double stimuli responsive hydrogel: by methylene-bisacrylamide (BIS), isopropyl acrylamide
The acrylamido azobenzene of amine, the alpha-cyclodextrin ester of step (1) preparation and step (2) preparation is added in dimethyl sulfoxide solution A,
Ultrasonic vibration dissolution, obtains mixed liquid B；Then it takes azobisisoheptonitrile (AVBN) to be added in dimethyl sulfoxide solution C again, is mixed
Close liquid D；Finally mixed liquor D is added in mixed liquid B, mixes and is reacted under the conditions of certain temperature in postposition water-bath, instead
Should after obtain photo-thermal double stimuli responsive hydrogel.
Preferably, in step (1) amount ratio of alpha-cyclodextrin used and dimethylformamide (DMF) be 1.94g:15~
20mL；The amount ratio of the triethylamine, acryloyl chloride and alpha-cyclodextrin is 2~3mL:1~2mL:1.94g.
Preferably, the time reacted at room temperature described in step (1) is 30~60min；The vacuum drying temperature
Degree is 60 DEG C~80 DEG C.
Preferably, the amount ratio of P-aminoazobenzene and benzene used is 1.97g:15~20mL in step (2)；Three second
The amount ratio of amine, acryloyl chloride and P-aminoazobenzene is 1.5~2.5mL:1~2mL:1.97g.
Preferably, certain temperature condition described in step (2) be 60 DEG C~80 DEG C, be stirred at reflux reaction time be 4~
6h。
Preferably, a vacuum drying temperature described in step (2) is 60 DEG C~80 DEG C.
Preferably, alpha-cyclodextrin ester described in step (3), acrylamido azobenzene, methylene-bisacrylamide, isopropyl
The amount ratio of base acrylamide and dimethyl sulfoxide solution A be 0.1g:0.05~0.1g:0.15~0.2g:0.6~0.8g:4~
7mL。
Preferably, the amount ratio of alpha-cyclodextrin ester, azobisisoheptonitrile and dimethyl sulfoxide solution C described in step (3) is
0.1g:0.05~0.1g:1~2mL.
Preferably, certain temperature described in step (3) is 50~60 DEG C, and the reaction time is 2~4h.
Wherein, dimethyl sulfoxide solution A and dimethyl sulfoxide solution C is dimethyl sulfoxide solution, adds alphabetical purpose and is table
Up to when distinguished.
The present invention has the advantages that
(1) present invention realizes a large amount of loads of the hydrogel to drug molecule, and cyclodextrin units are introduced in polymer network,
Cyclodextrin has outer wall is hydrophilic, inner cavity is a hydrophobic cyclic structure, drug molecule by and the combination of cyclodextrin cavity form main-visitor
Nanocrystal composition, to change the water solubility of guest molecule significantly.
(2) alpha-cyclodextrin and acryloyl chloride are synthesized alpha-cyclodextrin ester and acrylamido by esterification by the present invention
Azobenzene is as photosensitive component, using n-isopropyl acrylamide as temperature sensitive component, methylene-bisacrylamide as crosslinking agent,
Double stimuli responsive hydrogel a kind of while that there is temperature sensitivity and light-sensitive characteristic is generated by free radical polymerization, utilizes water
Cyclodextrin cavity in gel cross-linkage network structure improves the drug loading of hydrogel to the inclusion compound action of drug molecule
Amount, and together with temperature sensitive component and photosensitive component, pass through photosensitive complex owner-visitor in ambient temperature, illumination wavelength variation
The responsiveness of compound/dissociation and temperature sensitive component shrink/expanded between body changes to realize the controlled release to drug molecule,
So as to the carrier material in terms of as intelligent transdermal drug delivery.
(3) photo-thermal double stimuli responsive hydrogel prepared by the present invention introduces cyclodextrin and light, temperature configuration response simultaneously
Unit enables the carrier hydrogel of preparation largely to load drug molecule, and occurs in ambient temperature and illumination wavelength
When change, the responsiveness variation of drug molecule rate of release can be adjusted in time；Meanwhile provided by the present invention includes α-
The photo-thermal double stimuli responsive hydrogel of cyclodextrin is safe and environment-friendly, and has preferable stability, preparation process is easy to operate,
It is convenient.
Detailed description of the invention
Fig. 1 is the infrared spectrogram of the alpha-cyclodextrin ester with multiple double bonds prepared by embodiment 1.
Fig. 2 is the alpha-cyclodextrin ester with multiple double bonds prepared by embodiment 11H magnetic resonance spectroscopy figure.
Fig. 3 is the infrared spectrogram of acrylamido azobenzene prepared by embodiment 1.
Fig. 4 is acrylamido azobenzene prepared by embodiment 11H magnetic resonance spectroscopy figure.
Fig. 5 is the infrared spectrogram of photo-thermal double stimuli responsive hydrogel prepared by embodiment 1.
Fig. 6 is the structural schematic diagram of photo-thermal double stimuli responsive hydrogel prepared by embodiment 1.
Fig. 7 is after embodiment 1 prepares photo-thermal double stimuli responsive hydrogel load salicylic acid, and rate of release changes with temperature
Become and the releasing curve diagram of spontaneous carry out responsiveness variation.
Fig. 8 is after photo-thermal double stimuli responsive hydrogel prepared by embodiment 1 loads salicylic acid, and rate of release is with illumination
Wavelength shift and the release profiles of spontaneous carry out responsiveness variation.
Specific embodiment
The present invention is explained in further detail below with reference to specific embodiment.
Embodiment 1:
(1) preparation of alpha-cyclodextrin ester；
The alpha-cyclodextrin for weighing 1.94g is dissolved in 20mL dimethylformamide, and magnetic agitation makes it completely dissolved, and then drips
Add 3mL triethylamine, and places it in magnetic agitation 5min in 0 DEG C of ice-water bath and dripped under conditions of being passed through nitrogen protection with constant pressure
The acryloyl chloride of 2mL is slowly added dropwise into flask for liquid funnel, reacts 30min after being added dropwise to complete at room temperature, after reaction very
Empty pump filter removes and solid is precipitated, filters again after a large amount of acetone precipitations of filtrate, gained white solid repeatedly washs pumping with acetone
Filter, final product are placed in vacuum drying oven, and are dried at 70 DEG C to constant weight, are obtained alpha-cyclodextrin ester；
(2) preparation of acrylamido azobenzene；
1.97g P-aminoazobenzene is weighed to be dissolved in 20mL benzene, magnetic agitation completely it is molten after, the triethylamine of 1.5mL is added,
At room temperature, the acryloyl chloride of 1mL is slowly added dropwise dropwise simultaneously in magnetic agitation, 4h, reaction knot are then stirred at reflux at 60 DEG C
It is cooling after beam, it is filtered by vacuum and dry, uses a small amount of distillation water washing to filter gained Orange red solid twice and dry, then use
A small amount of dehydrated alcohol recrystallization, final product are placed in vacuum drying oven, dry at 60 DEG C to constant weight, obtain acrylamido azo
Benzene；
(3) preparation of photo-thermal double stimuli responsive hydrogel: alpha-cyclodextrin ester, the 0.1g acrylamido for weighing 0.1g are even
Pyridine, the methylene-bisacrylamide of 0.15g and 0.8g n-isopropyl acrylamide are dissolved in the dimethyl sulfoxide A of 3mL, are surpassed
Dissolution is swung in acoustic shock, obtains mixed liquid B；Then it takes the azobisisoheptonitrile of 0.05g to be added in the dimethyl sulfoxide solution C of 1mL again, obtains
To mixed liquor D；Finally mixed liquor D is added in mixed liquid B, mixes in postposition water-bath and carries out reaction 2h under the conditions of 55 DEG C,
Photo-thermal double stimuli responsive hydrogel is obtained after reaction.
Embodiment 2:
(1) preparation of alpha-cyclodextrin ester；
The alpha-cyclodextrin for weighing 1.94g is dissolved in the dimethylformamide of 15mL, and magnetic agitation makes it completely dissolved, then
2.5mL triethylamine is added dropwise, and places it in magnetic agitation 3min in 0 DEG C of ice-water bath, under conditions of being passed through nitrogen protection, with perseverance
The acryloyl chloride of 1.5mL is slowly added dropwise into flask for pressure dropping funel, reacts 20min, reaction knot after being added dropwise to complete at room temperature
It is filtered by vacuum after beam, removes and solid is precipitated, filtered again after a large amount of acetone precipitations of filtrate, gained white solid acetone is multiple
Washing filters, and final product is placed in vacuum drying oven, and dries at 60 DEG C to constant weight, obtains alpha-cyclodextrin ester；
(2) preparation of acrylamido azobenzene；
The P-aminoazobenzene for weighing 1.97g is dissolved in the benzene of 15mL, magnetic agitation completely it is molten after, be added tri- second of 2.5mL
Amine is slowly added dropwise the acryloyl chloride of 2mL dropwise simultaneously in magnetic agitation, 3h is then stirred at reflux at 60 DEG C, instead at room temperature
It is cooling after answering, it is filtered by vacuum and dry, uses a small amount of distillation water washing to filter gained Orange red solid twice and dry, so
It is recrystallized afterwards with a small amount of dehydrated alcohol, final product is placed in vacuum drying oven, and is dried at 60 DEG C to constant weight, is obtained acrylamido
Azobenzene；
(3) the alpha-cyclodextrin ester and 0.05g acrylamido of 0.1g the preparation of photo-thermal double stimuli responsive hydrogel: are weighed
Azobenzene, the methylene-bisacrylamide and 0.6g n-isopropyl acrylamide of 0.1g are dissolved in the dimethyl sulfoxide A of 3mL, are surpassed
Dissolution is swung in acoustic shock, obtains mixed liquid B；Then it takes the azobisisoheptonitrile of 0.08g to be added in the dimethyl sulfoxide solution C of 1mL again, obtains
To mixed liquor D；Finally mixed liquor D is added in mixed liquid B, mixes in postposition water-bath and carries out reaction 4h under the conditions of 60 DEG C,
Photo-thermal double stimuli responsive hydrogel is obtained after reaction.
Embodiment 3:
(1) preparation of alpha-cyclodextrin ester；
It weighs 1.94g alpha-cyclodextrin to be dissolved in the dimethylformamide of 18mL, magnetic agitation makes it completely dissolved, and then drips
Add the triethylamine of 2mL, and places it in magnetic agitation 3min in 0 DEG C of ice-water bath and use constant pressure under conditions of being passed through nitrogen protection
The acryloyl chloride of 1mL is slowly added dropwise into flask for dropping funel, reacts 40min after being added dropwise to complete at room temperature, after reaction
Vacuum filtration removes and solid is precipitated, filters again after a large amount of acetone precipitations of filtrate, gained white solid is repeatedly washed with acetone
It filters, final product is placed in vacuum drying oven, and is dried at 80 DEG C to constant weight, is obtained alpha-cyclodextrin ester；
(2) preparation of acrylamido azobenzene；
1.97g P-aminoazobenzene is weighed to be dissolved in 10mL benzene, magnetic agitation completely it is molten after, be added 1.5mL triethylamine, In
At room temperature, the acryloyl chloride of 1.5mL is slowly added dropwise dropwise simultaneously in magnetic agitation, 5h, reaction knot are then stirred at reflux at 60 DEG C
It is cooling after beam, it is filtered by vacuum and dry.Gained Orange red solid is twice and dry with a small amount of distillation water washing suction filtration, then use
A small amount of dehydrated alcohol recrystallization, final product are placed in vacuum drying oven, dry at 80 DEG C to constant weight, obtain acrylamido azo
Benzene；
(3) the alpha-cyclodextrin ester and 0.08g acrylamido of 0.1g the preparation of photo-thermal double stimuli responsive hydrogel: are weighed
Azobenzene, the methylene-bisacrylamide and 0.8g n-isopropyl acrylamide of 0.2g are dissolved in the dimethyl sulfoxide A of 5mL, are surpassed
Dissolution is swung in acoustic shock, obtains mixed liquid B；Then it takes the azobisisoheptonitrile of 0.1g to be added in the dimethyl sulfoxide solution C of 2mL again, obtains
To mixed liquor D；Finally mixed liquor D is added in mixed liquid B, mixes in postposition water-bath and carries out reaction 6h under the conditions of 50 DEG C,
Photo-thermal double stimuli responsive hydrogel is obtained after reaction.
Fig. 1 is the infrared spectroscopy of the cyclodextrin ester with multiple double bonds prepared by embodiment 1；In 1727cm-1Place occurs
The stretching band of C=O, 1657cm in ester group-1It is nearby the stretching band of C=C.3363cm-1The wide absorption peak at place
And 2928cm-1The needle-shaped absorption peak at place is hydroxyl and the stretching band of C-H respectively, these show that double bond has been successfully introduced into α-
On cyclodextrin.
Fig. 2 is the cyclodextrin ester with multiple double bonds prepared by embodiment 11H magnetic resonance spectroscopy；The position of each hydrogen atom
It sets:1H NMR(400MHz,D2O): δ (ppm)=6.39-6.22 (m, 1H, AA-H), 6.21-6.07 (m, 1H, AA-H), 6.07-
5.79 (m, 1H, AA-H), 4.89 (d, 1H, C (1) H of CD), 3.78 (s, 2H, C (3) H of CD), 3.78 (d, J=
8.8Hz, 8H, C (6) H of CD), 3.66 (d, J=9.0Hz, 5H, C (5) H of CD), 3.54 (d, J=10.0Hz, 4H, C
(2)H of CD),3.47-3.43(m,4H,C(4)H of CD)。
Fig. 3 is the infrared spectroscopy of acrylamido azobenzene prepared by embodiment 1；Wherein: 3200cm-1And 3135cm-1For
The stretching vibration of c h bond on carbon-carbon double bond；3070cm-1For the stretching vibration of c h bond on phenyl ring；1600cm-1And 1556cm-1For
The skeletal vibration of phenyl ring.985cm-1Have also appeared the bending vibration of monosubstituted alkene c h bond.In 3280cm-1And 1670cm-1Place
Occur the N-H key of amide groups and the stretching vibration peak of C=O respectively.
Fig. 4 is acrylamido azobenzene prepared by embodiment 11H magnetic resonance spectroscopy；A (5.78~5.84) is in the figure
Hydrogen peak on the double key carbon of carbonyl trans position, b (6.26~6.37) are the hydrogen peak on the double key carbon of carbonyl cis position, c
(6.45~6.52) are the hydrogen peaks on the double key carbon being connected with carbonyl, and g (7.46~7.55) and f (7.94~7.96) are the right benzene
Hydrogen peak on ring, d (7.77~7.82) and e (7.89~7.94) are hydrogen peaks on the phenyl ring of the left side.
Fig. 5 is the infrared spectroscopy of double stimuli responsive hydrogel prepared by embodiment 1；3280cm-1And 1670cm-1Place
The N-H key of amide groups and the stretching vibration peak and 3363cm of C=O-1The wide absorption peak of the hydroxyl at place and 2928cm-1The C-H needle at place
Shape absorption peak has appeared in the infrared spectroscopy of light and heat-sensitive hydrogel, illustrates that light and heat-sensitive hydrogel is successfully closed
At.
Fig. 6 is the structural schematic diagram of double stimuli responsive hydrogel prepared by embodiment 1；Wherein Photo-sensitive
Moiety is photosensitive part；Thermo-sensitive moiety is temperature-sensitive part.
Fig. 7 is after the hydrogel using this method preparation prepared by embodiment 1 loads salicylic acid, and rate of release is with temperature
Change and the release profiles of spontaneous carry out responsiveness variation；Rate of release of methylene blue under the conditions of 37 DEG C quickly, at 20 DEG C
Under the conditions of rate of release reduce, and this release can repeat to test it is multiple.The generation of this phenomenon and hydrogel be not
Reversible swelling under synthermal is related.
Fig. 8 is after the hydrogel using this method preparation prepared by embodiment 1 loads salicylic acid, and rate of release is with illumination
Wavelength shift and the release profiles of spontaneous carry out responsiveness variation；Rate of release of methylene blue under the conditions of 430nm is very fast, In
Rate of release under the conditions of 365nm is slower, and this release can repeat to test repeatedly.When system is by extraneous 430nm light
Wave irradiation after, azobenzene group from syn-isomerism be it is trans-, enter cyclodextrin cavity and squeeze out drug molecule, cause drug
Molecule is easier to be distributed in solution.The generation of this phenomenon and hydrogel azobenzene group structure under Compound eye are suitable
Anti-change is related.
Illustrate: above embodiments are only to illustrate the present invention and not limit the technical scheme described by the invention；Therefore,
Although this specification is referring to the above embodiments, the present invention has been described in detail, the ordinary skill people of this field
Member is it should be appreciated that still can modify to the present invention or equivalent replacement；And all do not depart from the spirit and scope of the present invention
Technical solution and its improvement, should all cover in scope of the presently claimed invention.
Claims (10)
1. a kind of preparation method comprising alpha-cyclodextrin photo-thermal double stimuli responsive hydrogel, which is characterized in that according to following steps
It is rapid to carry out:
(1) alpha-cyclodextrin is dissolved under magnetic stirring with dimethylformamide, triethylamine is then added dropwise, is placed in ice-water bath
Middle magnetic agitation is uniform, under conditions of being passed through nitrogen protection, then acryloyl chloride is slowly added dropwise, after being added dropwise to complete at room temperature into
Row reaction, is filtered by vacuum after reaction, filters again after collecting filtrate acetone precipitation, obtained white solid uses third again
Ketone repeated washing filters, and final product carries out being dried under vacuum to constant weight, obtains alpha-cyclodextrin ester；
(2) P-aminoazobenzene and benzene are added triethylamine, are slowly added dropwise simultaneously in magnetic agitation by dissolving under magnetic stirring
Then acryloyl chloride is stirred back flow reaction under the conditions of certain temperature, is cooled to room temperature after reaction, takes out through vacuum
Filter, it is dry after Orange red solid, then be washed with distilled water, filter after be dried, then recrystallized with dehydrated alcohol, finally
Product carries out being dried under vacuum to constant weight, obtains acrylamido azobenzene；
(3) it prepared by methylene-bisacrylamide, N-isopropylacrylamide, the alpha-cyclodextrin ester of step (1) preparation and step (2)
Acrylamido azobenzene be added dimethyl sulfoxide solution A in, ultrasonic vibration dissolution, obtain mixed liquid B；Then azo two is taken again
Different heptonitrile is added in dimethyl sulfoxide solution C, obtains mixed liquor D；Finally mixed liquor D is added in mixed liquid B, mixes postposition water-bath
It is reacted under the conditions of certain temperature in pot, photo-thermal double stimuli responsive hydrogel is obtained after reaction.
2. a kind of preparation method comprising alpha-cyclodextrin photo-thermal double stimuli responsive hydrogel according to claim 1,
It is characterized in that, the amount ratio of alpha-cyclodextrin and dimethylformamide used is 1.94g:15~20mL in step (1)；Three second
The amount ratio of amine, acryloyl chloride and alpha-cyclodextrin is 2~3mL:1~2mL:1.94g.
3. a kind of preparation method comprising alpha-cyclodextrin photo-thermal double stimuli responsive hydrogel according to claim 1,
It is characterized in that, the time reacted at room temperature described in step (1) is 30~60min；The vacuum drying temperature is 60
DEG C~80 DEG C.
4. a kind of preparation method comprising alpha-cyclodextrin photo-thermal double stimuli responsive hydrogel according to claim 1,
It is characterized in that, the amount ratio of P-aminoazobenzene and benzene used is 1.97g:15~20mL in step (2)；The triethylamine, third
The amount ratio of alkene acyl chlorides and P-aminoazobenzene is 1.5~2.5mL:1~2mL:1.97g.
5. a kind of preparation method comprising alpha-cyclodextrin photo-thermal double stimuli responsive hydrogel according to claim 1,
It is characterized in that, certain temperature condition described in step (2) is 60 DEG C~80 DEG C, and the time for being stirred at reflux reaction is 4~6h.
6. a kind of preparation method comprising alpha-cyclodextrin photo-thermal double stimuli responsive hydrogel according to claim 1,
It is characterized in that, a vacuum drying temperature described in step (2) is 60 DEG C~80 DEG C.
7. a kind of preparation method comprising alpha-cyclodextrin photo-thermal double stimuli responsive hydrogel according to claim 1,
It is characterized in that, alpha-cyclodextrin ester described in step (3), acrylamido azobenzene, methylene-bisacrylamide, isopropyl propylene
The amount ratio of amide and dimethyl sulfoxide solution A are 0.1g:0.05~0.1g:0.15~0.2g:0.6~0.8g:4~7mL.
8. a kind of preparation method comprising alpha-cyclodextrin photo-thermal double stimuli responsive hydrogel according to claim 1,
It is characterized in that, the amount ratio of alpha-cyclodextrin ester, azobisisoheptonitrile and dimethyl sulfoxide solution C described in step (3) is 0.1g:
0.05~0.1g:1~2mL.
9. a kind of preparation method comprising alpha-cyclodextrin photo-thermal double stimuli responsive hydrogel according to claim 1,
It is characterized in that, certain temperature described in step (3) is 50~60 DEG C, and the reaction time is 2~4h.
10. according to claim 1~9 method described in any one preparation hydrogel be applied to drug molecule load and
The rate of release of drug molecule is adjusted in drug delivery process.
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