CN111939310A - Polyvinyl alcohol-pectin embolism microsphere, medicine-carrying embolism microsphere and preparation method - Google Patents
Polyvinyl alcohol-pectin embolism microsphere, medicine-carrying embolism microsphere and preparation method Download PDFInfo
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- A61L24/001—Use of materials characterised by their function or physical properties
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Abstract
The invention discloses a polyvinyl alcohol-pectin embolism microsphere, a medicine-carrying embolism microsphere and a preparation method thereof, wherein the preparation method of the embolism microsphere comprises the following steps: mixing the polyvinyl alcohol solution and the pectin solution to obtain a water phase; dissolving the emulsifier in the continuous phase and mixing uniformly to obtain an oil phase; adding the water phase into the oil phase, and uniformly stirring to obtain a polyvinyl alcohol-pectin emulsion; dissolving a cross-linking agent glutaraldehyde and a catalyst hydrochloric acid in ether, and then dropwise adding the solution into polyvinyl alcohol-pectin emulsion for cross-linking reaction to obtain polyvinyl alcohol-pectin suspension; centrifuging and washing the polyvinyl alcohol-pectin suspension, and then freeze-drying to obtain the polyvinyl alcohol-pectin embolism microsphere. Dissolving the antitumor drug in water to obtain an antitumor drug solution, then placing the polyvinyl alcohol-pectin microspheres in the antitumor drug solution and stirring, and adsorbing the antitumor drug by the polyvinyl alcohol-pectin embolism microspheres to obtain the polyvinyl alcohol-pectin drug-loaded embolism microspheres. The prepared embolism microsphere has certain degradation capability and higher drug-loading rate.
Description
Technical Field
The invention belongs to the technical field of biomedicine and high polymer materials, and particularly relates to a polyvinyl alcohol-pectin embolism microsphere, a drug-loaded embolism microsphere and a preparation method thereof.
Background
In interventional therapy, transcatheter vascular embolization (TACE) is a very important treatment method, and mainly comprises injecting an embolization agent into a supply vessel of a diseased target organ through an arterial or intravenous catheter to occlude the vessel and interrupt blood supply, thereby finally achieving the treatment purpose.
When the TACE technology is used for treating tumors, chemotherapeutic drugs can be injected into the tumors besides blocking blood vessels, so that the blood supply of the tumors can be blocked, the tumors lack necessary nutrients, the killing power of the drugs on the tumors can be enhanced, and the systemic toxicity of the drugs is reduced. For the tumor which can not be removed by the surgical operation, the method can be used for treating the tumor, and the tumor can be reduced and removed by the surgical operation after being infused with the anti-tumor medicine; can also be used for intra-arterial perfusion chemotherapy for preventing recurrence after tumor resection. Currently, the most used is the treatment of liver cancer in the middle and late stages, especially for patients who miss the optimal surgical period or cannot tolerate surgery. Compared with the traditional therapy, the tumor interventional therapy has the advantages of minimal invasion, low cost, safety, good curative effect and the like, and particularly has special and important significance for tumor patients who cannot be operated.
Traditional TACE often uses iodized oil-chemotherapy drug mixed emulsion embolization, but has several major drawbacks: firstly, the iodized oil emulsion has local deposition, and the cytotoxic effect of the medicine on the tumor is reduced along with the prolonging of time; secondly, although the emulsion reduces the adverse reaction of the whole body compared with the traditional chemotherapy, part of the medicine still enters the circulatory system, and the adverse reaction is increased; and thirdly, in the tumor treatment, the treatment effect needs to maintain a certain drug concentration in the tumor, which depends on the sustained release of the drug, and the iodine oil emulsion is difficult to realize.
The medicine carrying embolism microsphere is one new kind of medicine preparation with excellent embolism function, and can carry chemotherapeutic medicine to reach high concentration in tumor cell and prolong the acting time between medicine and tumor cell. Polyvinyl alcohol embolism microsphere exists in the market at present, but the polyvinyl alcohol embolism microsphere is hardly degraded in vivo, meanwhile, the polyvinyl alcohol embolism microsphere does not contain active groups, the polyvinyl alcohol embolism microsphere needs to be activated or derivatized again before loading drugs, the process is complex, and the drug loading rate of the polyvinyl alcohol embolism microsphere is still low.
Disclosure of Invention
Aiming at the defects in the prior art, the invention aims to provide the polyvinyl alcohol-pectin embolism microsphere, the drug-loaded embolism microsphere and the preparation method thereof.
A preparation method of polyvinyl alcohol-pectin embolism microspheres comprises the following steps:
(1) dissolving polyvinyl alcohol in water to prepare a polyvinyl alcohol solution with the mass concentration of 1-20%; dissolving pectin in water to prepare a pectin solution with the mass concentration of 1-10%; then uniformly mixing the polyvinyl alcohol solution and the pectin solution to obtain a polyvinyl alcohol-pectin mixed solution for later use;
(2) dissolving an emulsifier in the continuous phase, and uniformly mixing to obtain an oil phase for later use; the emulsifier is one or two of Span 80 or tween 80, and the continuous phase is one or two of liquid paraffin, petroleum ether and vegetable oil;
(3) adding the polyvinyl alcohol-pectin mixed solution obtained in the step (1) into the oil phase obtained in the step (2), stirring at the speed of 300-5000 r/min, and uniformly stirring to obtain a polyvinyl alcohol-pectin emulsion;
(4) dissolving a cross-linking agent glutaraldehyde and a catalyst hydrochloric acid in ether to obtain a cross-linking solution, then dropwise adding the cross-linking solution into the polyvinyl alcohol-pectin emulsion obtained in the step (3) for cross-linking reaction to obtain a polyvinyl alcohol-pectin suspension, wherein the stirring speed is 300-5000 r/min, the temperature is 25-90 ℃, and the reaction time is 3-8 hours during the cross-linking reaction;
(5) and (4) centrifuging and washing the polyvinyl alcohol-pectin suspension obtained in the step (4), and then freeze-drying to obtain the polyvinyl alcohol-pectin embolism microspheres.
Further, the molecular weight of the pectin is lower than 20000 daltons, and the volume ratio of the polyvinyl alcohol solution to the pectin solution in the polyvinyl alcohol-pectin mixed solution is 1: 10-10: 1.
Further, the vegetable oil is one of soybean oil, corn oil or olive oil; the volume ratio of the emulsifier to the continuous phase in the oil phase is 0.1: 20-1: 20.
Further, in the step (3), the volume ratio of the polyvinyl alcohol-pectin mixed solution to the oil phase is as follows: 1: 100-30: 100.
Further, in the step (4), the concentration of hydrochloric acid is 0.1-5 mol/L, and the volume ratio of glutaraldehyde, hydrochloric acid and diethyl ether is 2:1: 5; the volume ratio of the ether to the polyvinyl alcohol-pectin emulsion is 0.2: 10-1: 10.
Further, washing with isopropanol, absolute ethanol and deionized water in this order, and repeating for a plurality of times.
A PVA-pectin embolization microsphere can be obtained according to the preparation method described above.
A preparation method of polyvinyl alcohol-pectin embolism drug-loaded microspheres comprises the steps of dissolving a water-soluble anti-tumor drug in water to obtain an anti-tumor drug solution, then placing the polyvinyl alcohol-pectin embolism microspheres in the anti-tumor drug solution, and stirring at a stirring speed of 100-1000 r/min, wherein the polyvinyl alcohol-pectin embolism microspheres adsorb the anti-tumor drug to obtain the polyvinyl alcohol-pectin drug-loaded embolism microspheres.
Further, the water-soluble antitumor drugs include, but are not limited to, doxorubicin hydrochloride, oxaliplatin, and irinotecan.
The polyvinyl alcohol-pectin drug-loaded embolism microsphere can be obtained according to the preparation method of the polyvinyl alcohol-pectin embolism drug-loaded microsphere.
Compared with the prior art, the invention has the following beneficial effects:
1. the polyvinyl alcohol-pectin embolism microsphere prepared by the invention has good biocompatibility, good elasticity and flexibility, certain degradation capability and higher drug loading capability, and has good antibacterial coagulation function on embolism microsphere and wound.
2. Pectin is the polysaccharide macromolecular substance that exists in the plant cell wall, is food level polymer nutrient substance, and biocompatibility is good to can degrade, make the embolism microballon that obtains of preparation have certain degradability, after the tumour treatment, pectin can degrade, thereby make the embolism microballon disintegrate, and then can be decomposed by internal enzyme and discharge extracorporeally, reduced the embolism microballon in the internal volume of remaining, reduced the injury to the human body.
Meanwhile, the pectin contains carboxyl, especially the micromolecular pectin (the molecular weight is less than 20000 daltons) contains a large number of carboxyl, has strong adsorption capacity on water-soluble antitumor drugs, especially water-soluble cationic antitumor drugs, can absorb the antitumor drugs through ion adsorption and swelling effects to improve the drug loading rate, and further ensures that the drug-loaded embolism microsphere has high drug loading rate. And the micromolecule pectin is a competitive inhibitor of the in-vivo galectin-3 ligand, has good tumor inhibiting capability, and can further improve the tumor treating effect in the treating process after the embolism microsphere is degraded in vivo.
In addition, the pectin has good antibacterial effect, the pectin also has anticoagulant and thrombolytic effects, and negatively charged groups in the pectin specifically interact with blood coagulation factors in blood, so that the activity of thrombin is inhibited, and the embolic microspheres and wound parts have good antibacterial and blood coagulation functions.
3. The invention can prepare embolization microspheres with different particle diameters by adjusting the process parameters of the volume ratio of the polyvinyl alcohol solution to the pectin solution, the volume ratio of the polyvinyl alcohol-pectin mixed solution to the oil phase, the stirring speed and the like, then loads the medicine for embolization control of tumors at different parts, and can continuously and slowly release the medicine at the tumor parts, thereby not only effectively reducing the side effect of the antitumor medicine in the treatment process, but also enhancing the passive accumulation of the medicine at the tumor parts, and further improving the transmission efficiency and the bioavailability of the medicine.
4. The embolism microsphere prepared by the invention can be directly used for loading drugs without derivatization, thereby simplifying the preparation process of the drug-loaded embolism microsphere and improving the preparation efficiency of the drug-loaded embolism microsphere.
Drawings
FIG. 1-scanning electron micrograph of PVA-pectin embolization microspheres prepared according to example 1.
FIG. 2-graph of the drug loading of P-P and PVA and Pectin prepared in example 1 as a function of time.
FIG. 3 is a scanning electron microscope image of the PVA-pectin embolization microspheres prepared in example 2.
FIG. 4 is a scanning electron microscope image of the PVA-pectin embolization microspheres prepared in example 3.
FIG. 5-scanning electron microscope image of the PVA-pectin embolization microspheres prepared in example 4.
Detailed Description
The present invention will be described in further detail with reference to the accompanying drawings and specific embodiments.
A preparation method of polyvinyl alcohol-pectin embolism microspheres comprises the following steps:
(1) dissolving polyvinyl alcohol in water to prepare a polyvinyl alcohol solution with the mass concentration of 1-20%; dissolving pectin in water to prepare a pectin solution with the mass concentration of 1-10%; then uniformly mixing the polyvinyl alcohol solution and the pectin solution to obtain a polyvinyl alcohol-pectin mixed solution for later use;
(2) dissolving an emulsifier in the continuous phase, and uniformly mixing to obtain an oil phase for later use; the emulsifier is one or two of Span 80 or tween 80, and the continuous phase is one or two of liquid paraffin, petroleum ether and vegetable oil;
(3) adding the polyvinyl alcohol-pectin mixed solution obtained in the step (1) into the oil phase obtained in the step (2), stirring at the speed of 300-5000 r/min, and uniformly stirring to obtain a polyvinyl alcohol-pectin emulsion;
(4) dissolving a cross-linking agent glutaraldehyde and a catalyst hydrochloric acid in ether to obtain a cross-linking solution, then dropwise adding the cross-linking solution into the polyvinyl alcohol-pectin emulsion obtained in the step (3) for cross-linking reaction to obtain a polyvinyl alcohol-pectin suspension, wherein the stirring speed is 300-5000 r/min, the temperature is 25-90 ℃, and the reaction time is 3-8 hours during the cross-linking reaction;
(5) and (4) centrifuging and washing the polyvinyl alcohol-pectin suspension obtained in the step (4), and then freeze-drying to obtain the polyvinyl alcohol-pectin embolism microspheres.
The pectin has degradation capability and can be degraded in vivo, and the polyvinyl alcohol-pectin embolization microspheres prepared from the polyvinyl alcohol also have certain degradation capability, after the pectin is degraded in vivo, the embolization microspheres are dispersed, and the pectin can be decomposed by enzymes in vivo and discharged out of the body, so that the residual quantity of the embolization microspheres in vivo is reduced.
Meanwhile, the pectin contains carboxylic acid, so that the pectin has good adsorption capacity on water-soluble antitumor drugs and has stronger adsorption capacity on water-soluble cationic antitumor drugs, thereby being beneficial to the drug loading of the embolism microspheres.
The polyvinyl alcohol-pectin mixed solution is used as a water phase, is usually added into an oil phase in a dropping or slow pouring mode, and is uniformly dispersed into a liquid drop shape in the oil phase under the stirring action, so that the subsequent emulsification and crosslinking are facilitated to form microspheres.
In specific implementation, the molecular weight of the pectin is lower than 20000 daltons, and the volume ratio of the polyvinyl alcohol solution to the pectin solution in the polyvinyl alcohol-pectin mixed solution is 1: 10-10: 1.
The pectin with the molecular weight lower than 20000 daltons is small molecular pectin, contains a large amount of carboxylic acid, has higher anti-tumor adsorption capacity than macromolecular pectin, and can effectively carry the drug load of anti-tumor drugs; and the micromolecule pectin also has certain capacity of inhibiting the growth of tumors, and after the embolism microspheres are degraded, the micromolecule pectin in the embolism microspheres can improve the treatment effect on the tumors.
Preferably, the polyvinyl alcohol-pectin mixed solution is prepared by mixing a polyvinyl alcohol solution with a mass concentration of 20% and a pectin solution with a mass concentration of 6%.
In specific implementation, the vegetable oil is one of soybean oil, corn oil or olive oil; the volume ratio of the emulsifier to the continuous phase in the oil phase is 0.1: 20-1: 20.
In the specific implementation, in the step (3), the volume ratio of the polyvinyl alcohol-pectin mixed solution to the oil phase is as follows: 1: 100-30: 100.
In the step (4), the concentration of hydrochloric acid is 0.1-5 mol/L, the volume ratio of glutaraldehyde, hydrochloric acid and diethyl ether is 2:1:5, and the volume ratio of diethyl ether and polyvinyl alcohol-pectin emulsion is 0.2: 10-1: 10.
In specific implementation, during washing, isopropanol, absolute ethyl alcohol and deionized water are adopted for washing in sequence, and the washing is repeated for multiple times.
And washing for multiple times to remove glutaraldehyde, hydrochloric acid, ether and emulsifier contained in the precipitate obtained after centrifugation, and continuously equalizing to obtain the polyvinyl alcohol-pectin embolism microsphere with higher purity.
Dissolving a water-soluble antitumor drug in water to obtain an antitumor drug solution, then placing the polyvinyl alcohol-pectin embolism microspheres in the antitumor drug solution, stirring at the stirring speed of 100-1000 r/min, and adsorbing the antitumor drug by the polyvinyl alcohol-pectin embolism microspheres to obtain the polyvinyl alcohol-pectin drug-loaded embolism microspheres.
Within a certain time range, the drug loading can be improved by prolonging the adsorption time and increasing the initial concentration of the drug, but the drug loading is finally determined by the performance of the embolization microsphere, such as the porosity of the microsphere and the content of carboxyl on the microsphere, namely the content of carboxyl on pectin
In specific implementation, the water-soluble antitumor drugs include, but are not limited to, doxorubicin hydrochloride, oxaliplatin and irinotecan.
The embolism microspheres with different particle diameters are prepared by adjusting the volume ratio of the polyvinyl alcohol solution to the pectin solution, the volume ratio of the polyvinyl alcohol-pectin mixed solution to the oil phase, the stirring speed and other process parameters, and the particle diameters of the prepared embolism microspheres are 20-100 microns, 100-300 microns, 300-500 microns, 500-700 microns and 700-900 microns.
Example 1
(1) Preparing a polyvinyl alcohol-pectin mixed solution: taking 10 mL of polyvinyl alcohol solution with the mass concentration of 10%, taking 10 mL of pectin solution with the mass concentration of 10%, stirring and mixing uniformly at the stirring speed of 500 r/min for 8 h, standing to remove bubbles, and obtaining polyvinyl alcohol-pectin mixed solution with certain viscosity;
(2) emulsification crosslinking: measuring 0.5 mL of emulsifier Span-80, dissolving in 50 mL of continuous phase liquid paraffin, and uniformly stirring to obtain an oil phase, wherein the rotating speed is 1000 r/min, and the stirring time is 20 min; and under the stirring state, dropwise adding the polyvinyl alcohol-pectin mixed solution into the oil phase, wherein the stirring speed is 1000 r/min, and the stirring time is 30 min, so that the polyvinyl alcohol-pectin is uniformly dispersed, and thus the polyvinyl alcohol-pectin emulsion is obtained. Dissolving 2 mL of glutaraldehyde and 1 mL of hydrochloric acid in 5 mL of diethyl ether to obtain a cross-linking agent solution, then dropwise adding the cross-linking agent solution into the polyvinyl alcohol-pectin emulsion for reaction, stirring at the rotation speed of 500 r/min, at the reaction temperature of 50 ℃, and reacting for 4 hours;
(3) washing, drying and screening: and after the reaction is finished, putting the reaction solution into a centrifuge for centrifugation, performing centrifugal washing on the precipitate by using isopropanol, absolute ethyl alcohol and deionized water for reversal, and then performing freeze drying to obtain the polyvinyl alcohol-pectin embolism microspheres. Screening the polyvinyl alcohol-pectin embolism microspheres to obtain embolism microspheres with uniform particle sizes;
(4) carrying out medicine loading: dissolving 1 g of adriamycin in water, dissolving 1 g of polyvinyl alcohol-pectin microspheres in adriamycin solution, and stirring at the stirring speed of 300 r/min to prepare the polyvinyl alcohol-pectin/adriamycin medicine-carrying embolism microspheres.
As shown in fig. 1, the scanning electron microscope image of the polyvinylalcohol-pectin embolization microspheres obtained in this example shows that the obtained embolization microspheres have good sphericity and smooth surfaces.
In addition, the polyvinyl alcohol embolism microsphere is obtained by adopting a single polyvinyl alcohol solution as an aqueous phase according to the preparation method of the example 1; the pectin embolization microspheres obtained by the preparation method of example 1 using a single pectin solution as the aqueous phase had good sphericity, whereas the pectin embolization microspheres were not completely spherical, because pectin has poor spheronization.
Carrying out drug loading experiments and swelling experiments on the polyvinyl alcohol-Pectin embolism microspheres (marked as P-P), the polyvinyl alcohol embolism microspheres (marked as PVA) and the Pectin embolism microspheres (marked as Pectin).
Drug loading experiments: carrying out medicine loading according to the step (4); the curve of the change of the drug loading rate with time in the process of loading the three embolism microspheres is shown in figure 2. As can be seen from the figure: compared with PVA, P-P has higher drug loading because of rich carboxyl groups on the micromolecular Pectin and has stronger adsorption capacity to cationic drugs, PVA prepared from a single polyvinyl alcohol solution has poorer adsorption capacity because of no active groups, and Pectin prepared from a single Pectin solution has ultrahigh drug loading.
Swelling ratio test: placing the cooled and dried P-P, PVA and Pectin in a vacuum drying oven for drying, removing water, weighing the weight of each microsphere, soaking the microspheres in deionized water for swelling, taking out the microspheres after swelling for 15min, sucking water attached to the surfaces of the microspheres by using absorbent paper, accurately weighing and recording the weight of each swollen microsphere again, and then calculating to obtain that the swelling rate of P-P is 189.3%, the swelling rate of PVA is 218.5% and the swelling rate of Pectin is 162.7%.
From the above, although Pectin has higher drug loading, the swelling ratio is obviously lower than that of P-P and PVA, and the Pectin is not easy to form balls, so that the single Pectin is not suitable for preparing the microspheres; compared with PVA, P-P has higher drug loading capacity and is more suitable for carrying drugs.
Example 2
(1) Preparing a polyvinyl alcohol-pectin mixed solution: taking 5 mL of polyvinyl alcohol solution with the mass concentration of 12% and 15 mL of pectin solution with the mass concentration of 10%, stirring and mixing uniformly at the stirring speed of 800 r/min for 8 h, and standing to remove bubbles to obtain a polyvinyl alcohol-pectin mixed solution with a certain viscosity;
(2) emulsification crosslinking: weighing 0.5 mL of emulsifier Span-80, dissolving in 80 mL of liquid paraffin, and uniformly stirring to obtain an oil phase, wherein the rotating speed is 800 r/min, and the stirring time is 30 min; and under the stirring state, dropwise adding the polyvinyl alcohol-pectin mixed solution into the oil phase, wherein the stirring speed is 1500 r/min, and the stirring time is 30 min, so that the polyvinyl alcohol-pectin emulsion is uniformly dispersed, and the polyvinyl alcohol-pectin emulsion is obtained. Dissolving 2.4 mL of glutaraldehyde and 1.2 mL of hydrochloric acid in 6 mL of ether to obtain a cross-linking agent solution, then dropwise adding the cross-linking agent solution into the polyvinyl alcohol-pectin emulsion for reaction, stirring at the rotating speed of 600 r/min, at the reaction temperature of 55 ℃ for 3 hours;
(3) washing, drying and screening: and after the reaction is finished, putting the reaction solution into a centrifuge for centrifugation, sequentially and centrifugally washing the precipitate with isopropanol, absolute ethyl alcohol and deionized water, repeating for many times, and then freeze-drying to obtain the polyvinyl alcohol-pectin embolism microspheres. Screening the polyvinyl alcohol-pectin embolism microspheres to obtain embolism microspheres with uniform particle sizes;
(4) carrying out medicine loading: dissolving 0.5 g of adriamycin in water, dissolving 2 g of polyvinyl alcohol-pectin embolism microspheres in adriamycin solution, and stirring at the stirring speed of 300 r/min to prepare the polyvinyl alcohol-pectin/adriamycin medicine-carrying embolism microspheres.
The scanning electron micrograph of the polyvinylalcohol-pectin embolization microspheres obtained in this example is shown in fig. 3.
Example 3
(1) Preparing a polyvinyl alcohol-pectin mixed solution: taking 2 mL of polyvinyl alcohol solution with the mass concentration of 20% and 18 mL of pectin solution with the mass concentration of 8%, stirring and mixing uniformly at the stirring speed of 500 r/min for 8 h, and standing to remove bubbles to obtain a polyvinyl alcohol-pectin mixed solution with a certain viscosity;
(2) emulsification crosslinking: weighing 0.8 mL of emulsifier Span-80, dissolving in 100 mL of soybean oil, and stirring uniformly to obtain an oil phase, wherein the rotating speed is 500 r/min, and the stirring time is 30 min; and dropwise adding the polyvinyl alcohol-pectin mixed solution into the oil phase under stirring, wherein the stirring speed is 3000 r/min, and the stirring time is 20 min, so that the polyvinyl alcohol-pectin mixed solution is uniformly dispersed, and the polyvinyl alcohol-pectin emulsion is obtained. Then dissolving 1.6 mL of glutaraldehyde and 0.8 mL of hydrochloric acid in 4 mL of ether to obtain a cross-linking agent solution, then dropwise adding the cross-linking agent solution into the emulsion for reaction, stirring at the rotating speed of 600 r/min, at the reaction temperature of 60 ℃ for 5 hours;
(3) washing, drying and screening: and after the reaction is finished, putting the reaction solution into a centrifuge for centrifugation, sequentially and centrifugally washing the precipitate with isopropanol, absolute ethyl alcohol and deionized water, repeating for many times, and then freeze-drying to obtain the polyvinyl alcohol-pectin embolism microspheres. Screening the polyvinyl alcohol-pectin embolism microspheres to obtain embolism microspheres with uniform particle sizes;
(4) carrying out medicine loading: dissolving 1 g of adriamycin in water, dissolving 3 g of polyvinyl alcohol-pectin embolism microspheres in the adriamycin solution, and stirring at the speed of 300 r/min to prepare the polyvinyl alcohol-pectin/adriamycin medicine-carrying embolism microspheres.
The scanning electron micrograph of the polyvinylalcohol-pectin embolization microspheres obtained in this example is shown in fig. 4.
Example 4
(1) Preparing a polyvinyl alcohol-pectin mixed solution: taking 18 mL of polyvinyl alcohol solution with the mass concentration of 20% and 2 mL of pectin solution with the mass concentration of 8%, stirring and mixing uniformly at the stirring speed of 500 r/min for 8 h, and standing to remove bubbles to obtain a polyvinyl alcohol-pectin mixed solution with a certain viscosity;
(2) emulsification crosslinking: weighing 0.6 mL of emulsifier Span-80, dissolving in 80 mL of liquid paraffin, and uniformly stirring to obtain an oil phase, wherein the rotating speed is 600 r/min, and the stirring time is 20 min; and dropwise adding the polyvinyl alcohol-pectin mixed solution into the oil phase under stirring, wherein the stirring speed is 1500 r/min, and the stirring time is 20 min, so that the polyvinyl alcohol-pectin mixed solution is uniformly dispersed, and the polyvinyl alcohol-pectin emulsion is obtained. Then dissolving 1.8 mL of glutaraldehyde and 0.9 mL of hydrochloric acid in 4.5 mL of ether to obtain a cross-linking agent solution, then dropwise adding the cross-linking agent solution into the polyvinyl alcohol-pectin emulsion for reaction, stirring at the rotating speed of 1000 r/min at the reaction temperature of 65 ℃ for 5 hours;
(3) washing, drying and screening: and after the reaction is finished, putting the reaction solution into a centrifuge for centrifugation, sequentially and centrifugally washing the precipitate with isopropanol, absolute ethyl alcohol and deionized water, repeating for many times, and then freeze-drying to obtain the polyvinyl alcohol-pectin embolism microspheres. Screening the polyvinyl alcohol-pectin embolism microspheres to obtain embolism microspheres with uniform particle sizes;
(4) carrying out medicine loading: dissolving 1.2 g of adriamycin in water, dissolving 2 g of polyvinyl alcohol-pectin microspheres in adriamycin solution, and stirring at the speed of 400 r/min to prepare the polyvinyl alcohol-pectin/adriamycin medicine-carrying embolism microspheres.
The scanning electron micrograph of the polyvinylalcohol-pectin embolization microspheres obtained in this example is shown in fig. 5.
Finally, it should be noted that the above-mentioned examples of the present invention are only examples for illustrating the present invention, and are not intended to limit the embodiments of the present invention. Variations and modifications in other variations will occur to those skilled in the art upon reading the foregoing description. Not all embodiments are exhaustive. All obvious changes and modifications of the present invention are within the scope of the present invention.
Claims (10)
1. A preparation method of polyvinyl alcohol-pectin embolism microspheres is characterized by comprising the following steps:
(1) dissolving polyvinyl alcohol in water to prepare a polyvinyl alcohol solution with the mass concentration of 1-20%; dissolving pectin in water to prepare a pectin solution with the mass concentration of 1-10%; then uniformly mixing the polyvinyl alcohol solution and the pectin solution to obtain a polyvinyl alcohol-pectin mixed solution for later use;
(2) dissolving an emulsifier in the continuous phase, and uniformly mixing to obtain an oil phase for later use; the emulsifier is one or two of Span 80 or tween 80, and the continuous phase is one or two of liquid paraffin, petroleum ether and vegetable oil;
(3) adding the polyvinyl alcohol-pectin mixed solution obtained in the step (1) into the oil phase obtained in the step (2), stirring at the speed of 300-5000 r/min, and uniformly stirring to obtain a polyvinyl alcohol-pectin emulsion;
(4) dissolving a cross-linking agent glutaraldehyde and a catalyst hydrochloric acid in ether to obtain a cross-linking solution, then dropwise adding the cross-linking solution into the polyvinyl alcohol-pectin emulsion obtained in the step (3) for cross-linking reaction to obtain a polyvinyl alcohol-pectin suspension, wherein the stirring speed is 300-5000 r/min, the temperature is 25-90 ℃, and the reaction time is 3-8 hours during the cross-linking reaction;
(5) and (4) centrifuging and washing the polyvinyl alcohol-pectin suspension obtained in the step (4), and then freeze-drying to obtain the polyvinyl alcohol-pectin embolism microspheres.
2. The method for preparing the polyvinyl alcohol-pectin embolization microspheres according to claim 1, wherein the molecular weight of the pectin is lower than 20000 daltons, and the volume ratio of the polyvinyl alcohol solution to the pectin solution in the polyvinyl alcohol-pectin mixed solution is 1: 10-10: 1.
3. The method for preparing polyvinylalcohol-pectin as to microspheres according to claim 1, wherein the vegetable oil is one of soybean oil, corn oil or olive oil; the volume ratio of the emulsifier to the continuous phase in the oil phase is 0.1: 20-1: 20.
4. The method for preparing the PVA-pectin embolization microspheres according to claim 1, wherein in the step (3), the volume ratio of the mixed solution of PVA-pectin to the oil phase is: 1: 100-30: 100.
5. The preparation method of the polyvinyl alcohol-pectin embolization microspheres according to claim 1, wherein in the step (4), the concentration of hydrochloric acid is 0.1-5 mol/L, and the volume ratio of glutaraldehyde, hydrochloric acid and diethyl ether is 2:1: 5; the volume ratio of the ether to the polyvinyl alcohol-pectin emulsion is 0.2: 10-1: 10.
6. The method for preparing PVA-pectin embolization microspheres according to claim 1, wherein the washing is carried out by sequentially washing with isopropanol, absolute ethyl alcohol and deionized water, and repeating for multiple times.
7. Polyvinyl alcohol-pectin embolization microspheres obtained by the preparation method according to claims 1-6.
8. A preparation method of polyvinyl alcohol-pectin embolism drug-loaded microspheres is characterized in that a water-soluble anti-tumor drug is dissolved in water to obtain an anti-tumor drug solution, then the polyvinyl alcohol-pectin embolism microspheres of claim 7 are placed in the anti-tumor drug solution to be stirred at a stirring speed of 100-1000 r/min, and the polyvinyl alcohol-pectin embolism microspheres adsorb the anti-tumor drug to obtain the polyvinyl alcohol-pectin drug-loaded embolism microspheres.
9. The method for preparing the PVA-pectin drug-loaded embolic microspheres of claim 8, wherein the water-soluble antitumor drug comprises but is not limited to doxorubicin hydrochloride, oxaliplatin and irinotecan.
10. Polyvinyl alcohol-pectin drug-loaded embolization microspheres obtained by the preparation method according to claim 9.
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112957517A (en) * | 2021-02-23 | 2021-06-15 | 苏州微尺度科技有限公司 | Embolism microsphere, preparation method thereof and drug-loaded embolism microsphere |
| CN113521378A (en) * | 2021-07-20 | 2021-10-22 | 上海益思妙医疗器械有限公司 | Preparation method of porous microspheres, microsphere embolic agent obtained by preparation method and application of microsphere embolic agent |
| CN113648283A (en) * | 2021-07-23 | 2021-11-16 | 丽水市中心医院 | Preparation method of drug-loaded microsphere for targeted inhibition of HIF-2 alpha, drug-loaded microsphere and application |
| CN114392384A (en) * | 2021-12-24 | 2022-04-26 | 河南驼人医疗器械研究院有限公司 | Method for preparing high drug-loading rate embolism microsphere and collecting device |
| CN115025297A (en) * | 2022-07-14 | 2022-09-09 | 青岛大学 | Light-emitting developing medicine-carrying four-in-one polyvinyl alcohol embolism microsphere and preparation method thereof |
| CN115068668A (en) * | 2022-06-08 | 2022-09-20 | 湖南工业大学 | Core-shell structure porous hydrogel embolization microsphere and preparation method thereof |
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20150224221A1 (en) * | 2012-08-31 | 2015-08-13 | Chung-Ang University Industry-Academic Cooperation Foundation | Method for preparing microspheres for emboli, and method for preparing microspheres to which drug-containing carrier is bound |
| CN105148327A (en) * | 2015-07-29 | 2015-12-16 | 陕西博与再生医学有限公司 | Preparation method of polysaccharide-polyvinyl alcohol embolism microsphere |
| CN108066314A (en) * | 2016-11-17 | 2018-05-25 | 中国科学院大连化学物理研究所 | A kind of pectin is the biological microsphere preparation method and application of wall material |
| CN109289081A (en) * | 2018-09-30 | 2019-02-01 | 华中科技大学鄂州工业技术研究院 | A kind of Polyvinyl Alcohol Embolization microballoon of resist blocking and that and its preparation method and application |
-
2020
- 2020-08-28 CN CN202010887116.7A patent/CN111939310A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20150224221A1 (en) * | 2012-08-31 | 2015-08-13 | Chung-Ang University Industry-Academic Cooperation Foundation | Method for preparing microspheres for emboli, and method for preparing microspheres to which drug-containing carrier is bound |
| CN105148327A (en) * | 2015-07-29 | 2015-12-16 | 陕西博与再生医学有限公司 | Preparation method of polysaccharide-polyvinyl alcohol embolism microsphere |
| CN108066314A (en) * | 2016-11-17 | 2018-05-25 | 中国科学院大连化学物理研究所 | A kind of pectin is the biological microsphere preparation method and application of wall material |
| CN109289081A (en) * | 2018-09-30 | 2019-02-01 | 华中科技大学鄂州工业技术研究院 | A kind of Polyvinyl Alcohol Embolization microballoon of resist blocking and that and its preparation method and application |
Non-Patent Citations (3)
| Title |
|---|
| TAPAN KUMAR GIRI DEEPA THAKUR ET AL: "biodegradable IPN hydrogel beads of pectin and grafted alginated for controlled delivery of diclofenac sodium", 《JOURNAL OF MATERIALS SCIENCE MATERIALS IN MEDICINE》 * |
| 孙贵范: "《助力癌症康复 1825+癌症的自然医学疗法策略 2018版》", 31 July 2018 * |
| 张力田: "《碳水化合物化学 第2版》", 31 July 2013 * |
Cited By (11)
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|---|---|---|---|---|
| CN112957517A (en) * | 2021-02-23 | 2021-06-15 | 苏州微尺度科技有限公司 | Embolism microsphere, preparation method thereof and drug-loaded embolism microsphere |
| CN113521378A (en) * | 2021-07-20 | 2021-10-22 | 上海益思妙医疗器械有限公司 | Preparation method of porous microspheres, microsphere embolic agent obtained by preparation method and application of microsphere embolic agent |
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| CN113648283B (en) * | 2021-07-23 | 2023-11-07 | 丽水市中心医院 | Preparation method of drug-loaded microsphere for targeted inhibition of HIF-2 alpha, drug-loaded microsphere and application |
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| CN114392384B (en) * | 2021-12-24 | 2023-04-11 | 河南驼人医疗器械研究院有限公司 | Method for preparing high drug-loading rate embolism microsphere and collecting device |
| CN115068668A (en) * | 2022-06-08 | 2022-09-20 | 湖南工业大学 | Core-shell structure porous hydrogel embolization microsphere and preparation method thereof |
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