CN109998987A - A kind of composite hydrogel and its preparation method and application based on natural konjaku flour - Google Patents
A kind of composite hydrogel and its preparation method and application based on natural konjaku flour Download PDFInfo
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Abstract
The present invention provides a kind of composite hydrogel and its preparation method and application based on natural konjaku flour.The composite hydrogel based on natural konjaku flour, it is characterized in that, preparation method includes: that photothermal conversion materiat and chemotherapeutics are dissolved in alkaline aqueous solution, be added konjaku flour, heating water bath or at room temperature stand obtain the composite hydrogel based on konjaku flour.It is raw material that the present invention, which takes the konjaku flour of dopamine and food-grade with good biocompatibility, and gelation process is simple to operation.Material safety is good, and gelation process is controllable, easy to operate, and the clinic that is more suitable converts.Other than the photo-thermal therapy to the solid tumor of middle and advanced stage/chemotherapy combined treatment can be achieved, this hydrogel is expected to block the blood vessel for the venous angioma being made of a large amount of lopsided blood vessels, plays the effect of tumor embolism treatment.
Description
Technical field
The present invention relates to Bio-Nano-Materials fields, are related to a kind of compound water congealing simple and easy to get based on natural konjaku flour
Glue and its preparation method and application.
Background technique
Cancer is most one of dangerous diseases of current threat human health.Operation, chemotherapy and radiation are current treatments of cancer
Several conventional means.However surgical operation, chemotherapy, radiotherapy, these morning are proved effective Underlying cancer therapy,
Its bring side effect often allows many patients to be difficult to bear.Operation can bring heavy burden or even patient to the body of patient
May in art, it is postoperative the complication such as occur infecting, even can be dead when serious.Chemotherapy and radiation method is current treating cancer
Two kinds of main means, but there is a series of deficiencies for both methods treating cancer.For chemotherapy, firstly, changing
Strong pain and toxic side effect can be brought to patient by treating drug, seriously affect its life quality；Secondly, current chemotherapeutics
Effective rate of utilization is totally poor, and cancer cell can generate drug resistance, with the development of chemotherapy, the decline of patient's constitution, immunity
Reducing can promote cancer cell to spread in turn again.Radiotherapy also has very big toxic side effect to biological organs, and cancer cannot be distinguished in X-ray
Attenuate born of the same parents and healthy cell, often will lead to normal tissue injury, and application range has significant limitation.It is increasingly chased after in people
It studies new cancer treatment method the today for seeking high-quality life, improves the quality of life of patient, extend the existence of tumor patient
Phase has important research and Practical significance.
As an effective alternative of traditional tumour treatment method, the photo-thermal therapy of tumour comes in this year by wide
General concern, principle are the optothermal materials that tumor locus is enriched in using near-infrared laser irradiation, utilize the photothermal conversion of material
The high heat that ability generates kills tumour cell.The photo-thermal therapy method of tumour has at low cost, targeting strong (especially pair
In some organs for being difficult to carry out resection operation), Small side effects the characteristics of.Utilize a kind of material with high photothermal conversion efficiency
Material, is injected into inside of human body, is gathered in tumor vicinity using targeting identification technology, and (usually close in external light source
Infrared light) irradiation under can convert light energy into amount of heat to killing cancer cell.However since optothermal material is not easy
Tumor locus accumulation for a long time or the shortage of heat quickly removed, and generated are to utterly destroy cancer cell to therapeutic effect
It is bad.So optothermal material should also be as having following advantage: firstly, most important is exactly to have good photothermal conversion effect
Rate, this is the key that this material is applied；Secondly, should nontoxic or only lower bio-toxicity, this material will be applied to
In organism, once it is more toxic；Material answers easy functionalization, can be in other molecules of its surface modification, and such as drug molecule is photosensitive
Agent etc..
Hydrogel system is the gel using water as decentralized medium as one of Typical Representative, has cross-linked network knot
A part of hydrophobic grouping and hydrophilic residue, hydrophilic residue and water molecules are introduced in the water soluble polymer of structure, by hydrone
It is connected to netted inside, and the cross-linked polymer of hydrophobic group water-swellable.It is a kind of macromolecule network system, property is soft, energy
Certain shape is kept, a large amount of water can be absorbed without being dissolved in water, compared with general delivery system, injectable water
Gel has many unique advantages.First, aquogel system has good biocompatibility, easily prepared, can target note
Enter tumour.Second, which can be with high-efficient carrier chemotherapeutic agent, as long as the chemotherapeutic agent can be dispersed in for giving birth to
In the solvent for producing gel.It, can be in certain outside stimulus since gel has typical swelling property under biotic factor
The release of lower triggering and control drug.
Dopamine is that a kind of neurotransmitter has in vivo for helping the chemical substance of cell transfer pulse
There is good compatibility.Imitating with good photothermal conversion for black is generated using the auto polymerization reaction of dopamine under alkaline condition
The poly-dopamine of fruit.Dopamine is widely used in material surface coating and participates in forming composite material.
Summary of the invention
The purpose of the invention is to provide a kind of composite hydrogel based on natural konjaku flour and preparation method thereof and answer
With.
In order to achieve the above object, the present invention provides a kind of composite hydrogel based on natural konjaku flour, feature exists
In preparation method includes: that photothermal conversion materiat and chemotherapeutics are dissolved in alkaline aqueous solution, and konjaku flour, water-bath is added
It heats or stands at room temperature and obtain the composite hydrogel based on konjaku flour.
Preferably, the photothermal conversion materiat is poly-dopamine, is occurred in alkaline solution by Dopamine hydrochloride certainly
Polymerization reaction and obtain.
Preferably, the chemotherapeutics is the anticancer drug for dissolving in the alkaline aqueous solution.
Preferably, the anticancer drug be Calciumlevofolinate, 5-Fluorouracil, doxorubicin hydrochloride, furan fluorouracil with
And at least one of Perarubicin, 5-Fluorouracil and Calciumlevofolinate more preferably with synergy.
Preferably, the heating water bath time is 5-30 minutes, and time of repose is 1-3 hours at room temperature.
The present invention also provides the preparation methods of the above-mentioned composite hydrogel based on natural konjaku flour, which is characterized in that
Include:
Step 1: chemotherapeutics being added in the sodium hydrate aqueous solution of pH=9-13, stirring is allowed to dissolve, and must contain
The mixed solution of chemotherapeutics；
Step 2: the resulting mixed solution of step 1 is added in Dopamine hydrochloride powder, stirring makes its polymerization, obtains black
Mixed solution；
Step 3: konjaku flour being added in the resulting mixed solution of step 2, stirring or concussion are allowed to uniformly mixed, water-bath
Heating is stood at room temperature, obtains the composite hydrogel based on konjaku flour.
Preferably, the concentration of the sodium hydrate aqueous solution in the step 1 is 0.00001-0.1mol/L, more preferably
0.1mol/L。
Preferably, the dispersion concentration of chemotherapeutics is 0.1-10mg/mL in the mixed solution in the step 1, more excellent
It is selected as 5mg/mL.
Preferably, the dispersion concentration of Dopamine hydrochloride is 1-5mg/mL, more preferable 2 mg/mL in the step 2.
Preferably, in the step 3 konjaku flour mass percent concentration be 3-5%, more preferably 4%.
Preferably, water bath heating temperature is 45 DEG C -60 DEG C in the step 3.
Preferably, the stirring in the step 2 is magnetic agitation, and rate is 50-400 revs/min, and mixing time is
3-5h, more preferably 5h.
The present invention also provides above-mentioned, and the composite hydrogel based on konjaku flour is used as load anti-tumor drug or photo-thermal
The purposes of converting material carrier.
The present invention selects with good biocompatibility, edible konjaku high molecular material to be matrix, with optothermal material
It is dissolved in solvent simultaneously with chemotherapeutics and obtains mixed solution.This mixed solution can gradually gelation under field conditions (factors),
The composite hydrogel of package optothermal material and chemotherapeutics is formed in vitro.The gelation process of this kind of composite hydrogel is not used
Organic solvent, biocompatibility with higher.In terms of material system, collect the generation of optothermal material, the generation of hydrogel, changes
Chemotherapy sensitizing caused by the solubilising and Calciumlevofolinate (CF) of drug is treated in one.Optothermal material photothermal conversion effect with higher
Rate can assign konjaku hydrogel good photothermal conversion ability；Two kinds of chemotherapeutics have synergy and can be from again
It closes and is slowly released in gel and generate certain curative effect to tumour.In clinical conversion aspect, the present invention, which takes, to be had well
The dopamine of biocompatibility and the KGM of food-grade be raw material, gelation process is easy to operate.Material safety is good, gel
Change process control, easy to operate, the clinic that is more suitable converts.In addition to photo-thermal therapy/change to the solid tumor of middle and advanced stage can be achieved
It treats outside combination therapy, this hydrogel is expected to block the blood vessel for the venous angioma being made of a large amount of lopsided blood vessels, plays swollen
The effect of tumor embolotherapy.
The present invention is compared with prior art, and technological progress is significant.
Konjaku hydrogel be it is a kind of there is biocompatibility, nontoxic or even edible material, can hybrid medicine be injected into
In human body.Currently, loading optothermal material and chemotherapeutics with konjaku hydrogel, the research in tumor combined therapeutic field is realized also
Similar report had not been met.
The present invention based on the KGM hydrogel with tumor thermal therapy, chemotherapy synergistic therapeutic effect, by it is single because
Sub (pH value) carrys out the solubilising of the generation of synchronously control hydrogel, the generation of optothermal material and chemotherapeutics.The present invention, which takes, to be had
The dopamine of good biocompatibility and the konjaku flour of food-grade are raw material, and gelation process is simple to operation.Material peace
Good perfection, gelation process is controllable, easy to operate, and the clinic that is more suitable converts.In addition to can be achieved to the solid tumor of middle and advanced stage
Photo-thermal therapy/chemotherapy combined treatment is outer, and this hydrogel is expected to block the venous angioma being made of a large amount of lopsided blood vessels
Blood vessel plays the effect of tumor embolism treatment.The present invention can effectively solve efficient, the lesser target of toxicity lacked in current technology
The problem limited to transportation system and oncotherapy technology.
Detailed description of the invention
In Fig. 1, (a-d) is konjaku hydrogel, the konjaku hydrogel for loading optothermal material poly-dopamine respectively, loads anti-swell
The konjaku hydrogel of tumor medicine 5-Fluorouracil and Calciumlevofolinate and the konjaku for loading optothermal material and anti-tumor drug simultaneously
Hydrogel SEM picture.
In Fig. 2, (a) is the picture of konjaku hydrogel；(b) it is the picture of the konjaku hydrogel of load dopamine, (c) is
The picture of the konjaku hydrogel of chemotherapeutics is loaded, is (d) picture of load chemotherapeutics and the konjaku hydrogel of dopamine.
In Fig. 3, (a) is to load the konjaku hydrogel of poly-dopamine under the 808nm laser irradiation of different capacity density, temperature
The curve changed over time is spent, (b) is photothermal imaging figure corresponding with (a).
In Fig. 4, (a) is that load poly-dopamine konjaku hydrogel photo and thermal stability under the irradiation of 808nm near-infrared laser is surveyed
Test result is (b) photothermal conversion efficiency of the konjak gel of load poly-dopamine.
In Fig. 5, (a) is to load the cell security test of dopamine konjaku hydrogel as a result, (b) being blank control
DEAD/LIVE cell dyeing is as a result, (c) for the DEAD/LIVE cell dyeing that handle by konjac glucomannan as a result, (d) be that process is born
Carry the DEAD/LIVE cell dyeing result of the konjac glucomannan processing of poly-dopamine.
In Fig. 6, (a) be through load different materials konjaku hydrogel processing L929 cell survival rate, (b) without
Processing；(c) the konjac glucomannan processing through overload 5-Fluorouracil；(d) konjaku through overload Calciumlevofolinate and 5-Fluorouracil
Glue processing；(e) konjac glucomannan through overload poly-dopamine handles and passes through laser irradiation；(f) through overload and Calciumlevofolinate,
5-Fluorouracil and the konjac glucomannan of poly-dopamine and DEAD/LIVE cell dyeing result Jing Guo laser irradiation.
The haemolysis test result of the konjak gel of Fig. 7 display load dopamine.
In Fig. 8, (a) is (medium pH=7.4 and pH=5.4) at different conditions for loading dopamine konjaku hydrogel
5-Fluorouracil release profiles, (b) for load dopamine konjaku hydrogel (medium pH=7.4 and pH at different conditions
=5.4) Calciumlevofolinate release profiles.It (c-f) is the konjak gel containing 5-Fluorouracil and the konjaku containing Calciumlevofolinate
Gel and konjak gel simultaneously containing 5-Fluorouracil and Calciumlevofolinate in 8h, for 24 hours, the superposition of the drug release of 48h it is purple
Outside-visible spectrum.
In Fig. 9, (a) is the konjaku hydrogel and load 5-Fluorouracil, Calciumlevofolinate and poly-dopamine for loading dopamine
Konjac glucomannan and pure konjac glucomannan in Mice Body with (808nm, 1W/cm under laser irradiation2) curve that changes over time of temperature,
It (b) is photothermal imaging figure corresponding with (a).It (c) is the change curve of the gross tumor volume for the mouse treated by distinct methods,
It (d) is pictorial diagram corresponding with (c).
Specific embodiment
Present invention will be further explained below with reference to specific examples.It should be understood that these embodiments are merely to illustrate the present invention
Rather than it limits the scope of the invention.In addition, it should also be understood that, after reading the content taught by the present invention, those skilled in the art
Member can make various changes or modifications the present invention, and such equivalent forms equally fall within the application the appended claims and limited
Range.
Used each raw material is commercial product in following embodiment.
Embodiment 1
0.4g konjaku flour is weighed to be added in the sodium hydrate aqueous solution that 10mL concentration is 0.1mol/L, it is quiet under 45 DEG C of water-baths
It sets 5min and obtains konjaku hydrogel.SEM observes result (Fig. 1 a) display, and obtained konjaku hydrogel (KGM) presents and do not advise
Then structure.
20mg Dopamine hydrochloride is weighed, is dissolved in the sodium hydrate aqueous solution that 10mL concentration is 0.1mol/L, at room temperature
It polymerize it naturally with revolving speed 200rpm magnetic agitation 5h, obtains the poly-dopamine solution of black.Add 0.4g konjaku flour, 45
5min is stood under DEG C water-bath obtains load poly-dopamine konjaku hydrogel (PDA KGM).SEM observes result (Fig. 1 b) display,
Irregular structure is presented in obtained compound konjaku hydrogel.
50mg Calciumlevofolinate, 50mg 5-Fluorouracil are weighed, the sodium hydroxide water that 10mL concentration is 0.1mol/L is added to
In solution, stir to dissolve.0.4g konjaku flour is added after it is completely dissolved, and 5min is stood under 45 DEG C of water-baths and is born
Carry the konjaku hydrogel (5-FU&CF@KGM) of Calciumlevofolinate and 5-Fluorouracil.SEM observes result (Fig. 1 c) display, acquired
Compound konjaku hydrogel present irregular structure.
50mg 5-Fluorouracil is weighed, is added in the sodium hydrate aqueous solution that 10mL concentration is 0.1mol/L, stirring makes
It is dissolved.0.4g konjaku flour is added after it is completely dissolved, and 5min is stood under 45 DEG C of water-baths and obtains load 5-Fluorouracil
Konjaku hydrogel (5-FU@KGM).
50mg Calciumlevofolinate is weighed, is added in the sodium hydrate aqueous solution that 10mL concentration is 0.1mol/L, stirring makes it
Dissolution.0.4g konjaku flour is added after it is completely dissolved, it is to obtain the evil spirit of load Calciumlevofolinate that 5min is stood under 45 DEG C of water-baths
Taro hydrogel (CF@KGM).
50mg Calciumlevofolinate, 50mg 5-Fluorouracil are weighed, the sodium hydroxide water that 10mL concentration is 0.1mol/L is added to
It in solution (pH=13), stirs to dissolve, obtains the mixed solution containing chemotherapeutics, 20mg hydrochloric acid is added after being completely dissolved
Dopamine polymerize it naturally at room temperature with revolving speed 200rpm magnetic agitation 5h, obtains the mixed solution of black, then 0.4g is magic
Taro powder is added in resulting mixed solution, and stirring is allowed to uniformly mixed, and 45 DEG C of heating water baths stand 5min and obtain load Asia
The composite hydrogel (PDA/5-FU&CF@KGM) based on konjaku flour of Calcium Folinate-SF, 5-Fluorouracil and poly-dopamine.SEM observation
As a result (Fig. 1 d) is shown, irregular structure is presented in obtained compound konjaku hydrogel.
Embodiment 2
KGM, PDA@KGM, 5-FU&CF@KGM and PDA/5-FU&CF@KGM hydrogel are prepared respectively according to embodiment 1.?
KGM, PDA/KGM, 5-FU&CF/KGM, PDA/5-FU&CF/KGM solution are alkaline solution before forming gel, easily sucking injection
Device has syringeability, as shown in Fig. 2 a-d left figure.KGM, PDA/KGM, 5-FU&CF/KGM, PDA/5-FU&CF/KGM these
Mixed solution (Fig. 2 a-d, left bottle), placement is gradually sticky after five minutes, and mobility reduces to form hydrogel (Fig. 2 a-d, right bottle).
Embodiment 3
The konjaku flour hydrogel (PDA KGM) of the resulting load poly-dopamine of 100 μ L embodiment 1 is taken to be placed in the training of 96 hole cells
It supports in plate.0.3W/cm is used respectively2、0.5W/cm2、0.8W/cm2And 1.0W/cm2808nm near-infrared laser irradiate hydrogel 5
Minute, it is changed with time relationship (Fig. 3) with FLIR E60 type thermal infrared imager record gelling temp, power is bigger, and hydrochloric acid is more
Bar amine optothermal material more efficiently can carry out photothermal conversion and increase the temperature of hydrogel, and the corresponding temperature difference respectively reaches
11.3℃,24.2℃,38.6 ℃,46.7℃。
Embodiment 4
The konjaku hydrogel (PDA@KGM) of the resulting load poly-dopamine of 100 μ L embodiment 1 is taken to be placed in 96 hole cell culture
In plate, and 100 μ L physiological saline are added.With laser (808nm, 1W/cm2) irradiation hydrogel 5 minutes, then stop irradiation making its from
It so cools 5 minutes, altogether repetitive cycling 10 times, is changed with time with FLIR E60 type thermal infrared imager record gelling temp
Relationship (Fig. 5 a), it can be seen that the trend of every group of circulation is essentially identical, and hydrogel shows good photo and thermal stability.It takes again
The resulting konjaku hydrogel (KGM) of 100 μ L embodiment 1 is placed in 96 porocyte culture plates, and 100 μ L physiological saline are added.With swash
Light (808nm, 1W/cm2) irradiation 5 minutes, then stop irradiation 5 minutes, as blank control, with FLIR E60 type thermal infrared imager
Record gelling temp changes with time relationship (Fig. 4 b), is computed, the konjaku water of the resulting load poly-dopamine of embodiment 1
The photothermal conversion efficiency of gel (PDA@KGM) reaches 42.6%, shows good photothermal conversion performance.
Embodiment 5
L929 cell is placed in 96 porocyte culture plates.It abandons 1640 culture mediums of script and 100 μ L of addition is fresh
1640 culture mediums, then take 1 resulting konjak gel (KGM) of 0.1g embodiment and load konjaku hydrogel (the PDA@of poly-dopamine
KGM) respectively with 1 × 104For 24 hours, control group is not dealt with a L929 cell co-culture.CCK-8 test the result shows that, through reality
Apply 1 resulting konjak gel (KGM) of example and load poly-dopamine konjaku hydrogel (PDA@KGM) co-incubation come out
The survival rate of L929 cell reaches 97.2 ± 3.8% and 97.7 ± 1.3%, and LIVE/DEAD cell activity coloration result also indicates that
Most cells are all dyed to green (survival), almost without red cell (death) is dyed to, it was demonstrated that material has good
Cell compatibility (Fig. 5).
Embodiment 6
Take konjac glucomannan (5-FU@KGM), (2) load of 0.1g embodiment 1 resulting (1) load 5-Fluorouracil sub- respectively
The konjaku hydrogel (5FU&CF@KGM) of Calcium Folinate-SF and 5-Fluorouracil, (3) load poly-dopamine konjac glucomannan (PDA@KGM),
(4) composite hydrogel (PDA/5FU&CF@KGM) based on konjaku flour of Calciumlevofolinate, 5-Fluorouracil and poly-dopamine is loaded
Respectively with 1 × 104A HT29 cell co-culture for 24 hours, wherein load poly-dopamine material 1W/cm2, 808nm NIR laser
Irradiation five minutes.Cell survival rate is detected with CCK-8 method, it can be clearly seen that, 5-Fluorouracil and Calciumlevofolinate
It is used in conjunction with, the survival rate of cell is lower, illustrates that two kinds of anticancer drugs have synergy, while carrying out photo-thermal therapy again, right
The fragmentation effect of cell is stronger (Fig. 6 a).In LIVE/DEAD cell activity coloration result, urinated through overload Calciumlevofolinate, five fluorine
Pyrimidine and the composite hydrogel based on konjaku flour of poly-dopamine handle and carry out laser irradiation cell be largely dyed to it is red
Color illustrates that the collective effect of photo-thermal therapy and chemotherapy produces good therapeutic effect (Fig. 6 f) to cancer cell.
Embodiment 7
Stable normal adults whole blood 1mL is taken, centrifugation 3 minutes (revolving speed is 3000 revs/min), uses brine
Precipitating 3 times, obtains erythrocyte.With physiological saline according to proportional arrangement adult's erythrocyte suspension of 1:50, in 4 DEG C of refrigerators
It is spare.The konjaku hydrogel of poly-dopamine is loaded obtained in embodiment 1 after weighing the freeze-drying of 2 groups of certain mass respectively
The resulting konjaku hydrogel (KGM) of embodiment 1 after (PDA KGM) and freeze-drying, then addition 0.3mL people is blood red into above-mentioned material
(control group setting 0.3mL human red cell suspension is dissolved in 1.2mL physiological saline for cell suspension and 1.2mL physiological saline
In and 0.3mL human red cell suspension be dissolved in 1.2mL distilled water), and be incubated for 1h under 37 DEG C of environment.After handling
Human red cell suspension be centrifuged 1 minute (3000 revs/min), take supernatant and with 25 type uv-spectrophotometric of Lamada
Light absorption value of the measurement examination supernatant at 540nm, to evaluate the hemolytic of material.(Fig. 7) is as can be seen that distilled water can make
Human red cell rises brokenly (hemolysis rate 100%) completely, embodiment 1 resulting konjaku hydrogel (KGM) and load poly-dopamine
The hemolysis rate of konjaku hydrogel (PDA@KGM) is lower than 1%, illustrates konjaku hydrogel (KGM) and loads the konjaku water of poly-dopamine
Gel (PDA@KGM) has good blood compatibility.
Embodiment 8
Take obtained in 12 groups of 0.5g embodiments 1 respectively load Calciumlevofolinate, 5-Fluorouracil and poly-dopamine based on
The composite hydrogel (PDA/5-FU&CF@KGM) of konjaku flour is put into bag filter, then is placed it in equipped with citrate buffer solution (pH
=5.4) in the sample bottle of (6 groups).Then, sample bottle is placed in the isothermal vibration device of 37 DEG C (3 groups) and 50 DEG C (3 groups) and is shaken
It swings.To compare aquogel system to the slow releasing function of drug, then 0.5mL (5mg/mL) 5-Fluorouracil and (5mg/mL) are taken respectively
(0.1 mol/L) sodium hydroxide solution of Calciumlevofolinate is placed directly in bag filter, and threading fills 5mL PBS solution (pH=
7.4) in sample bottle, then sample bottle is placed in 37 DEG C of isothermal vibration device.At pre-designed time point, from reagent bottle
In respectively take out 1mL solution, and supplement the new buffer of 1mL.
With ultraviolet-visible spectrophotometer test the 1mL sustained-release liquid of above-mentioned taking-up maximum absorption wavelength (Calciumlevofolinate:
282nm；5-Fluorouracil: 265nm) at light absorption value, the anti-tumor drug released is calculated according to standard curve, draw
Release kinetics profile of the gel to anti-tumor drug out.
Again with the monitoring of same method in pH=5.4, at a temperature of 37 DEG C and 54 DEG C, embodiment 1 is resulting same
When load Calciumlevofolinate (CF) and 5-Fluorouracil (5-FU) konjaku hydrogel (5-FU&CF@KGM) and respectively load Asia
The konjaku hydrogel (5-FU@KGM, CF@KGM) of Calcium Folinate-SF and 5-Fluorouracil in 8h, for 24 hours, the ultraviolet-ray visible absorbing light of 48h
Spectrum.
It can be seen that load Calciumlevofolinate, 5-Fluorouracil and poly- DOPA obtained in embodiment 1 from Fig. 8-a, Fig. 8-b
The composite hydrogel based on konjaku flour of amine can preferably control the rate of release of anti-tumor drug, this is for improving chemotherapeutic
The oncotherapy effect of object, reduction poisonous side effect of medicine are very important.It can be seen that the release of 5-FU and CF from Fig. 8 c-f
Amount is independent of each other, and has good synergy.
Embodiment 9
Take experimental group (1), (2), (3), (4) and control group (5) mouse, every group each 3.
Wherein, it is resulting in the tumor locus of mouse to inject 0.1mL embodiment 1 respectively for experimental group (1), (2), (3), (4)
It loads the konjac glucomannan (5-FU@KGM) of 5-Fluorouracil, load the konjaku hydrogel (5-FU& of Calciumlevofolinate and 5-Fluorouracil
CF@KGM), the konjac glucomannan (PDA@KGM) of load poly-dopamine, load Calciumlevofolinate, 5-Fluorouracil and poly-dopamine based on
The composite hydrogel (PDA/5-FU&CF@KGM) of konjaku flour, control group mice is not dealt with.
Wherein experimental group (3), every group of mouse of (4) and control group (5) carry out five minutes laser irradiation (808nm,
1W/cm2), the temperature that illuminated tumor locus is recorded with thermal infrared imager changes with time, it can be seen that contains anticarcinogen
The influence that object generates the photo-thermal effect of poly-dopamine is little (Fig. 9 a, b).These processed mouse pass through normal feeding in 28 days
It supports, compared with the control group, the growth of tumour receives apparent inhibition (Fig. 9 c, d), wherein through overload Calciumlevofolinate, five fluorine
The cases of complete remission of the composite hydrogel based on konjaku flour and the mouse Jing Guo laser irradiation of uracil and poly-dopamine,
Illustrate the method that photo-thermal therapy and chemotherapy combine, has good result to the treatment of tumour, there is certain practical significance.
Claims (10)
1. a kind of composite hydrogel based on natural konjaku flour, which is characterized in that preparation method includes: by photothermal conversion materiat
Be dissolved in alkaline aqueous solution with chemotherapeutics, be added konjaku flour, heating water bath or at room temperature stand obtain based on konjaku flour
Composite hydrogel.
2. the composite hydrogel as described in claim 1 based on natural konjaku flour, which is characterized in that the photothermal conversion material
Material is poly-dopamine, and auto polymerization reaction occurs in alkaline solution by Dopamine hydrochloride and obtains.
3. the composite hydrogel as described in claim 1 based on natural konjaku flour, which is characterized in that the chemotherapeutics is
The anticancer drug of the alkaline aqueous solution is dissolved in, the anticancer drug is Calciumlevofolinate, 5-Fluorouracil, hydrochloric acid Ah mould
At least one of element, furan fluorouracil and Perarubicin.
4. the composite hydrogel as described in claim 1 based on natural konjaku flour, which is characterized in that when the described heating water bath
Between be 5-30 minutes, at room temperature time of repose be 1-3 hours.
5. the preparation method of the composite hydrogel of any of claims 1-4 based on natural konjaku flour, feature exist
In, comprising:
Step 1: chemotherapeutics being added in the sodium hydrate aqueous solution of pH=9-13, stirring is allowed to dissolve, and must contain chemotherapy
The mixed solution of drug；
Step 2: the resulting mixed solution of step 1 is added in Dopamine hydrochloride powder, stirring makes its polymerization, obtains the mixing of black
Solution；
Step 3: konjaku flour being added in the resulting mixed solution of step 2, stirring or concussion are allowed to uniformly mixed, heating water bath
Or stand at room temperature, obtain the composite hydrogel based on konjaku flour.
6. the preparation method of the composite hydrogel as claimed in claim 5 based on natural konjaku flour, which is characterized in that described
The dispersion concentration of chemotherapeutics is 0.1-10mg/mL in mixed solution in step 1.
7. the preparation method of the composite hydrogel as claimed in claim 5 based on natural konjaku flour, which is characterized in that described
The dispersion concentration of Dopamine hydrochloride is 1-5mg/mL in step 2.
8. the preparation method of the composite hydrogel as claimed in claim 5 based on natural konjaku flour, which is characterized in that described
The mass percent concentration of konjaku flour is 3-5% in step 3.
9. the preparation method of the composite hydrogel as claimed in claim 5 based on natural konjaku flour, which is characterized in that described
Water bath heating temperature is 45 DEG C -60 DEG C in step 3.
10. composite hydrogel of any of claims 1-4 based on konjaku flour as load anti-tumor drug or
The purposes of photothermal conversion materiat carrier.
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