CN111110660A - Preparation method of selenium-loaded chitosan microspheres with slow release effect - Google Patents
Preparation method of selenium-loaded chitosan microspheres with slow release effect Download PDFInfo
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Abstract
The invention discloses a preparation method of selenium-loaded chitosan microspheres with a slow release effect, which comprises the following steps: s1, dissolving selenate and polyvinyl alcohol in a mixed solution of alcohol and water to form a solution A; s2, dissolving chitosan in an aqueous solution containing an emulsifier to form a solution B; s3, dripping the solution B into the solution A, and uniformly stirring to obtain a mixed solution; s4, adding a cross-linking agent into the mixed solution, stirring at 30-50 ℃, adding a dispersing agent into the mixed solution after a precipitate is formed, and performing ultrasonic treatment to form solid particles; and S5, after filtering, collecting solid particles, and air-drying to obtain the selenium-loaded chitosan microspheres with the slow release effect. The chitosan microsphere can stably release selenium-containing medicines in the chitosan microsphere for a long period of time, the encapsulation rate of the selenium-containing medicines is up to more than 70%, and the leakage probability of the selenium-containing medicines from a chitosan outer membrane is greatly reduced.
Description
Technical Field
The invention belongs to the field of sustained release of medicines, and particularly relates to a preparation method of selenium-loaded chitosan microspheres with a sustained release effect.
Background
Chitosan (CS) is the only natural polycation alkalescent polysaccharide, has physiological activities of hemostasis, bacteriostasis and the like in vivo, has no toxicity, good biocompatibility and degradability, and is known as one of the drug-carrying materials with the best application prospect. The research at home and abroad prepares chitosan into micro/nanospheres and other targeted drug delivery sustained-release materials, plays an important role in the aspects of drug delivery, sustained release, controlled release and the like, can be used as carriers of common drugs (such as famotidine, naproxen, metronidazole, indomethacin, aspirin, ibuprofen and the like), carriers of biological macromolecular drugs (such as vaccines, proteins and polypeptides) and carriers of anticancer drugs (such as mitomycin, cisplatin, paclitaxel, camptothecin and the like), and experiments prove that the micro/nanospheres can improve the drug stability, slowly release and target the drugs to action sites in vivo, maintain the long-term activity of the drugs and protect the drugs from the damage of digestive tract enzymes and the influence of pH values. The optimization and the application of the preparation process parameters of the chitosan microspheres are important directions for the research of the drug sustained-release functional materials in the future.
Selenium is one of indispensable elements for human bodies, and firstly, the selenium has an anti-oxidation effect and is a common anti-aging substance; secondly, selenium can enhance the immunity of the human body; in addition, selenium also has the function of regulating protein synthesis, and if the selenium element is lacked, protein energy deficiency malnutrition or chromosome damage and the like can be caused; thirdly, the selenium element is also beneficial to enhancing the reproductive and reproductive functions; finally, selenium can regulate the effects of vitamin A, vitamin C, vitamin E and the like, and the lack of selenium can cause myopia, cataract, retinopathy, eyeground diseases and the like, so that the selenium can be properly supplemented for a human body, and the selenium-enriched health tea has the advantages. However, excessive intake of selenium is likely to cause poisoning of the subject who has ingested it, which is harmful to the body. At present, the selenium-containing medicament has strong efficacy but the dosage is difficult to control, the encapsulation efficiency is usually low (50-70 percent), and the situation that the selenium-containing medicament leaks from the outer membrane in large quantity is possibly caused. The above two possibilities greatly increase the uncontrollable property of selenium-containing drugs.
Therefore, it is highly desirable to find a method for slowly and stably releasing selenium-containing drugs over a long period of time to solve the above problems.
Disclosure of Invention
The invention provides a selenium-loaded chitosan microsphere with stable slow release capability and higher encapsulation efficiency, which can stably release selenium-containing medicines in the chitosan microsphere for a long period of time, has the encapsulation efficiency of the selenium-containing medicines of more than 70 percent, and greatly reduces the leakage probability of the selenium-containing medicines from a chitosan outer membrane.
The present invention is realized by the following technical means.
A preparation method of a selenium-loaded chitosan microsphere with a slow release effect comprises the following steps:
s1, dissolving selenate and polyvinyl alcohol in a mixed solution of alcohol and water to form a solution A;
s2, dissolving chitosan in an aqueous solution containing an emulsifier to form a solution B;
s3, dripping the solution B into the solution A, and uniformly stirring to obtain a mixed solution;
s4, adding a cross-linking agent into the mixed solution, stirring at 30-50 ℃, adding a dispersing agent into the mixed solution after a precipitate is formed, and performing ultrasonic treatment to form solid particles;
and S5, after filtering, collecting solid particles, and air-drying to obtain the selenium-loaded chitosan microspheres with the slow release effect.
Further, the selenate is selected from sodium selenate, potassium selenate or magnesium selenate.
Further, the polyvinyl alcohol is modified polyvinyl alcohol, and the specific modification steps are as follows:
(1) blending polyvinyl alcohol and citric acid to form a mixed solution, wherein the citric acid accounts for 0.1-1% of the polyvinyl alcohol;
(2) adding concentrated sulfuric acid into the mixed solution, heating the mixed solution to 90-100 ℃, and reacting for 3-5h to form polyvinyl alcohol containing polyethylene glycol citrate;
(3) the polyvinyl alcohol containing polyethylene glycol citrate was adjusted to pH 7-8 to obtain a modified polyvinyl alcohol.
Further, characterized in that the emulsifier is selected from span or tween type emulsifiers.
Further, the chitosan polysaccharide is characterized in that selenate accounts for 2-5 wt% of chitosan; the polyvinyl alcohol accounts for 5-10 wt% of the chitosan.
Further characterized in that the number average molecular weight of the polyethylene glycol is greater than 400.
Further characterized in that the cross-linking agent is selected from glyoxal, malondialdehyde, succindialdehyde, or glutaraldehyde.
Further characterized in that the chitosan is selected from carboxymethylated chitosan, hydroxyethylated chitosan, or sulfonated chitosan.
The invention has the following beneficial effects:
the chitosan and the polyvinyl alcohol have good synergistic effect, so that the chitosan and the polyvinyl alcohol have obvious effects on the slow release of selenate and the improvement of the encapsulation rate of the selenate. Specifically, the method comprises the following steps: under the action of aldehyde crosslinking agent, chitosan forms a body type copolymer with a net structure. The structures of the chitosan and the polyvinyl alcohol both have a large amount of hydroxyl groups, so that hydrogen bonds between molecules with high density are easily formed between the chitosan and the polyvinyl alcohol, and the composite material formed by the chitosan and the polyvinyl alcohol has excellent compatibility, so that the mechanical properties of the chitosan and the polyvinyl alcohol are well fused: on one hand, the composite material has good rigidity and fibrous property of chitosan, and is not easy to deform, and the network structure formed by the chitosan can be used as a stable skeleton, so that the formed selenium-loaded chitosan microspheres are not easy to obviously deform, and the encapsulation rate of selenate and the controllability of the release speed are improved; on the other hand, the composite material has good toughness and film forming property of polyvinyl alcohol, so that the composite material is not easy to break, and the formed film has certain toughness and elasticity, and is beneficial to realizing a slow release mechanism.
Particularly, the modified polyvinyl alcohol disclosed by the invention is preferably doped with a polyethylene glycol derivative with a star-shaped macromolecular structure, and the polyethylene glycol derivative with the star-shaped macromolecular structure is prepared by esterification reaction of citric acid of polyvinyl alcohol accounting for 0.1-1% of the mass of the system and a very small part of polyvinyl alcohol. The polyethylene glycol derivative with the star-shaped macromolecular structure can be used in a composite material formed by chitosan and polyvinyl alcohol, and has the following functions: (1) the polyvinyl alcohol modified by citric acid esterification is a star-shaped polymer, has a highly irregular branched structure, and has three branched chains, so that the composite material formed by chitosan and polyvinyl alcohol can be infiltrated from a three-dimensional direction at the same time, the regularity of the composite material is thoroughly destroyed, and a large-range crystal region is formed due to regular structure in the process of forming a precipitate by crosslinking of the composite material, so that the brittleness and the toughness of a film formed by the composite material are increased, and the slow-release effect is weakened. However, since the linear polyvinyl alcohol does not have the highly irregular branched structure and can only penetrate into the composite material in the plane direction, the regularity of the composite material formed by chitosan and polyvinyl alcohol is limited, and the technical effect of the polyethylene glycol derivative with the star-shaped macromolecular structure cannot be achieved; (2) after the selenate is encapsulated by the chitosan microspheres, the selenate generally has the tendency of aggregating to form clusters, so that the slow release rate is uncontrollable, and the polyethylene glycol derivative with the star-shaped macromolecular structure can be effectively inserted among the micromolecule selenates to serve as a barrier to prevent the micromolecule selenates from aggregating to form clusters on one hand; on the other hand, the micromolecule selenate is easy to entangle due to the long molecular chain, so that the micromolecule selenate is effectively attached to the polyethylene glycol derivatives with the star-shaped macromolecular structure, and when the chitosan microspheres are dissolved in a human body, the polyethylene glycol derivatives with the star-shaped macromolecular structure are gradually dissolved, so that the free micromolecule selenate is gradually released, and the slow release effect of the selenate is enhanced.
Detailed Description
The present invention is further illustrated by the following specific examples, which are not intended to limit the invention in any way. The starting materials and methods described in the examples herein are, unless otherwise indicated, conventional in the art.
Example 1
A preparation method of a selenium-loaded chitosan microsphere with a slow release effect comprises the following steps:
s1, dissolving 2g of selenate and 5g of polyvinyl alcohol in a mixed solution of 100g of ethanol and water (the mass ratio of the ethanol to the water is 1:1) to form a solution A, wherein the number average molecular weight of the polyvinyl alcohol is 400.
S2, dissolving 100g of carboxymethylated chitosan in 500g of aqueous solution containing 0.5g of emulsifier span-20 to form solution B;
s3, dripping the solution B into the solution A, and uniformly stirring to obtain a mixed solution;
s4, adding 1g of cross-linking agent glyoxal into the mixed solution, stirring at 30 ℃, adding 0.5g of dispersing agent carboxymethyl cellulose into the mixed solution after a precipitate is formed, and performing ultrasonic treatment to form solid particles;
and S5, after filtering, collecting solid particles, and air-drying to obtain the selenium-loaded chitosan microspheres with the slow release effect.
Wherein, the polyvinyl alcohol is modified polyvinyl alcohol, and the specific modification steps are as follows:
(1) blending polyvinyl alcohol and citric acid of the polyvinyl alcohol to form a mixed solution, wherein the citric acid accounts for 0.1 percent of the substance of the polyvinyl alcohol;
(2) adding concentrated sulfuric acid which is 0.1 wt% of a reaction substrate into the mixed solution, heating the mixed solution to 90 ℃, and reacting for 3 hours to form polyvinyl alcohol containing polyethylene glycol citrate;
(3) the polyvinyl alcohol containing polyethylene glycol citrate was adjusted to pH 7.0 to obtain a modified polyvinyl alcohol.
Example 2
A preparation method of a selenium-loaded chitosan microsphere with a slow release effect comprises the following steps:
s1, dissolving 5g of selenate and 10g of polyvinyl alcohol in 100g of mixed solution of propanol and water (the mass ratio of the propanol to the water is 2:1) to form a solution A, wherein the number average molecular weight of the polyvinyl alcohol is 2000.
S2, dissolving 100g of hydroxyethylated chitosan into 500g of aqueous solution containing 0.5g of span-80 emulsifier to form solution B;
s3, dripping the solution B into the solution A, and uniformly stirring to obtain a mixed solution;
s4, adding 1.5g of cross-linking agent malondialdehyde into the mixed solution, stirring at 50 ℃, adding 0.5g of dispersant hydroxyethyl cellulose into the mixed solution after a precipitate is formed, and performing ultrasonic treatment to form solid particles;
and S5, after filtering, collecting solid particles, and air-drying to obtain the selenium-loaded chitosan microspheres with the slow release effect.
Wherein, the polyvinyl alcohol is modified polyvinyl alcohol, and the specific modification steps are as follows:
(1) blending polyvinyl alcohol and citric acid of the polyvinyl alcohol to form a mixed solution, wherein the citric acid accounts for 1% of the substance of the polyvinyl alcohol;
(2) adding concentrated sulfuric acid which is 0.3 wt% of a reaction substrate into the mixed solution, heating the mixed solution to 100 ℃, and reacting for 5 hours to form polyvinyl alcohol containing polyethylene glycol citrate;
(3) the polyvinyl alcohol containing polyethylene glycol citrate was adjusted to pH 8.0 to obtain a modified polyvinyl alcohol.
Example 3
A preparation method of a selenium-loaded chitosan microsphere with a slow release effect comprises the following steps:
s1, dissolving 4g of selenate and 8g of polyvinyl alcohol in a mixed solution of 100g of ethanol and water (the mass ratio of the ethanol to the water is 2.5:1) to form a solution A, wherein the number average molecular weight of the polyvinyl alcohol is 1500.
S2, dissolving 100g of sulfonated chitosan in 500g of aqueous solution containing 0.5g of emulsifier Tween-80 to form solution B;
s3, dripping the solution B into the solution A, and uniformly stirring to obtain a mixed solution;
s4, adding 1.5g of cross-linking agent succinaldehyde into the mixed solution, stirring at 40 ℃, adding 0.5g of dispersant polyacrylamide into the mixed solution after a precipitate is formed, and performing ultrasonic treatment to form solid particles;
and S5, after filtering, collecting solid particles, and air-drying to obtain the selenium-loaded chitosan microspheres with the slow release effect.
Wherein, the polyvinyl alcohol is modified polyvinyl alcohol, and the specific modification steps are as follows:
(1) blending polyvinyl alcohol and citric acid of the polyvinyl alcohol to form a mixed solution, wherein the citric acid accounts for 0.5 percent of the substance of the polyvinyl alcohol;
(2) adding concentrated sulfuric acid which is 0.2 wt% of a reaction substrate into the mixed solution, heating the mixed solution to 95 ℃, and reacting for 4 hours to form polyvinyl alcohol containing polyethylene glycol citrate;
(3) the polyvinyl alcohol containing polyethylene glycol citrate was adjusted to pH 7.5 to obtain a modified polyvinyl alcohol.
Example 4
A preparation method of a selenium-loaded chitosan microsphere with a slow release effect comprises the following steps:
s1, dissolving 3g of selenate and 6g of polyvinyl alcohol in 100g of mixed solution of methanol and water (the mass ratio of the methanol to the water is 3:1) to form a solution A, wherein the number average molecular weight of the polyvinyl alcohol is 1200.
S2, dissolving 100g of sulfonated chitosan in 500g of aqueous solution containing 0.5g of emulsifier Tween-20 to form solution B;
s3, dripping the solution B into the solution A, and uniformly stirring to obtain a mixed solution;
s4, adding 1.5g of cross-linking agent succinaldehyde into the mixed solution, stirring at 40 ℃, adding 0.7g of dispersant polyacrylamide into the mixed solution after a precipitate is formed, and performing ultrasonic treatment to form solid particles;
and S5, after filtering, collecting solid particles, and air-drying to obtain the selenium-loaded chitosan microspheres with the slow release effect.
Wherein, the polyvinyl alcohol is modified polyvinyl alcohol, and the specific modification steps are as follows:
(1) blending polyvinyl alcohol and citric acid of the polyvinyl alcohol to form a mixed solution, wherein the citric acid accounts for 0.8 percent of the substance of the polyvinyl alcohol;
(2) adding concentrated sulfuric acid which is 0.5 wt% of the reaction substrate into the mixed solution, heating the mixed solution to 92 ℃, and reacting for 4.5 hours to form polyvinyl alcohol containing polyethylene glycol citrate;
(3) the polyvinyl alcohol containing polyethylene glycol citrate was adjusted to pH 7.2 to obtain a modified polyvinyl alcohol.
Example 5
A preparation method of a selenium-loaded chitosan microsphere with a slow release effect comprises the following steps:
s1, dissolving 2.5g of selenate and 6.5g of polyvinyl alcohol in 100g of mixed solution of methanol and water (the mass ratio of the methanol to the water is 1.5:1) to form solution A, wherein the number average molecular weight of the polyvinyl alcohol is 1700.
S2, dissolving 100g of sulfonated chitosan in 500g of aqueous solution containing 0.5g of emulsifier Tween-20 to form solution B;
s3, dripping the solution B into the solution A, and uniformly stirring to obtain a mixed solution;
s4, adding 1.5g of cross-linking agent glyoxal into the mixed solution, stirring at 45 ℃, adding 0.7g of dispersant hydroxyethyl cellulose into the mixed solution after a precipitate is formed, and performing ultrasonic treatment to form solid particles;
and S5, after filtering, collecting solid particles, and air-drying to obtain the selenium-loaded chitosan microspheres with the slow release effect.
Wherein, the polyvinyl alcohol is modified polyvinyl alcohol, and the specific modification steps are as follows:
(1) blending polyvinyl alcohol and citric acid of the polyvinyl alcohol to form a mixed solution, wherein the citric acid accounts for 1.0 percent of the substance of the polyvinyl alcohol;
(2) adding concentrated sulfuric acid which is 0.4 wt% of the reaction substrate into the mixed solution, heating the mixed solution to 94 ℃, and reacting for 3.5 hours to form polyvinyl alcohol containing polyethylene glycol citrate;
(3) the polyvinyl alcohol containing polyethylene glycol citrate was adjusted to pH 7.8 to obtain a modified polyvinyl alcohol.
Comparative example 1
Comparative example 1 is the same as the preparation method of example 1 except that polyvinyl alcohol is not contained in the preparation method S1 of comparative example 1.
Comparative example 2
Comparative example 2 is the same as the preparation method of example 1 except that in S3 of the preparation method of comparative example 2, polyvinyl alcohol is not modified but only a linear polymer.
Comparative example 3
Comparative example 3 is prepared in the same manner as in example 1, except that the polyvinyl alcohol of comparative example 3 has a number average molecular weight of 200.
Comparative example 4
Comparative example 4 is prepared in the same manner as in example 1, except that in the step (1) of modifying polyvinyl alcohol of comparative example 4, polyvinyl alcohol is blended with acetic acid to form a mixed solution.
Comparative example 5
Comparative example 5 is prepared in the same manner as in example 1, except that in the step (1) of modifying polyvinyl alcohol of comparative example 5, polyvinyl alcohol is blended with oxalic acid to form a mixed solution.
Comparative example 6
Comparative example 6 is the same as the preparation method of example 1 except that in step S2 of polyvinyl alcohol modification of comparative example 6, the solution B does not contain an emulsifier.
Comparative example 7
Comparative example 7 was prepared in the same manner as in example 1, except that the chitosan of comparative example 7 was a common chitosan which had not been subjected to carboxymethylation, hydroxyethylation and sulfolation.
Example 6
The release rate and encapsulation efficiency of the selenium-loaded chitosan microspheres of examples 1 to 5 and comparative examples 1 to 7 were examined, wherein,
the test method of the release rate is as follows: 1.000g of each of the selenium-loaded chitosan microspheres of examples 1 to 5 and comparative examples 1 to 7 was accurately weighed as a sample, and each of the samples was put into a dialysis bag, and both ends of the dialysis bag were fastened. Respectively placing the solution in 200ml of 0.5% acetic acid solution by mass, respectively taking 1ml of the acetic acid solution of the 10 samples after 3 hours, measuring the concentration of free selenate at 280nm by using an ultraviolet spectrophotometer, converting the concentration into the amount of the free selenate in the solution, and calculating the release rate according to the following formula:
p ═ amount of free selenate/amount of selenate 100%
The method for testing the encapsulation efficiency comprises the following steps: several centrifuge tubes were prepared, and to each of the centrifuge tubes, 0.05g of the liposome samples of examples 1 to 5 and comparative examples 1 to 7, which were precisely weighed, and 3ml of an acetic acid solution were added to form a mixed solution, followed by centrifugation at 3000rpm for 30 min. Taking the supernatant, measuring the concentration of free selenate at the wavelength of 280nm by using an ultraviolet spectrophotometer, converting the concentration into the amount of the free selenate, and calculating the encapsulation efficiency according to the following encapsulation efficiency formula:
(amount of total selenate-amount of free selenate)/amount of total selenate 100%
The results obtained are shown in table 1.
TABLE 1 Release and encapsulation Rate results for examples 1-5 and comparative examples 1-7
| Release Rate (%) | Encapsulation efficiency (%) | |
| Example 1 | 34.5 | 73.6 |
| Example 2 | 32.7 | 70.2 |
| Example 3 | 34.0 | 71.2 |
| Example 4 | 35.5 | 75.6 |
| Example 5 | 38.7 | 72.4 |
| Comparative example 1 | 40.2 | 53.4 |
| Comparative example 2 | 42.1 | 65.3 |
| Comparative example 3 | 37.3 | 68.1 |
| Comparative example 4 | 36.7 | 68.9 |
| Comparative example 5 | 36.3 | 68.5 |
| Comparative example 6 | 39.0 | 59.3 |
| Comparative example 7 | 40.1 | 61.3 |
As can be seen from the table above, the release rates of the examples 1 to 5 are all about 30 to 40 percent, and the encapsulation rate is more than 70 percent; while comparative examples 1 to 7 are improvements based on example 1, it can be found that comparative examples 1 to 7 are all inferior to example 1 to a different extent in terms of technical effects. Specifically, comparative example 1 does not contain polyvinyl alcohol, and thus a composite material formed between chitosan and polyvinyl alcohol in example 1 cannot exist, so that the liposome of comparative example 1 does not have the toughness and good film-forming property described in example 1, resulting in a fragile composite material, and thus a sustained-release mechanism is affected; in comparative example 2, because the polyvinyl alcohol is not modified, the polyvinyl alcohol does not contain the polyethylene glycol derivative with the star-shaped macromolecular structure, and as described in the beneficial effects of the invention, the existence of the polyethylene glycol derivative with the star-shaped macromolecular structure can destroy the regularity of the composite material and prevent selenate from aggregating, so that the related technical effect of comparative example 2 is weaker than that of example 1; in comparative example 3, the number average molecular weight of the polyvinyl alcohol is too small, and the density of the formed hydrogen bond is too low, so that the compatibility of the composite material is deficient, the formed liposome has stronger brittleness, and the toughness and the film-forming property are poor, so that the slow-release effect is influenced; in comparative examples 4 to 5, polyvinyl alcohol reacted with acetic acid to form only a linear polymer, and a polyethylene glycol derivative having a star-shaped macromolecular structure according to claim 1 could not be formed. However, as mentioned in the beneficial effects of the present invention, the polyethylene glycol derivative with star-shaped macromolecular structure can play the following role in the composite material formed by chitosan and polyvinyl alcohol: (1) due to the fact that the chitosan/polyvinyl alcohol composite material has an irregular branched structure, the chitosan/polyvinyl alcohol composite material can be mixed in a composite material formed by chitosan and polyvinyl alcohol, the regularity of the composite material can be damaged, and a large-range crystal region is prevented from being formed due to the regular structure in the process that the composite material is crosslinked to form precipitates, so that the brittleness and the toughness of a film formed by the composite material are increased, and the slow-release effect is weakened; (2) after the selenate is encapsulated by the chitosan microspheres, the selenate generally has the tendency of aggregating to form clusters, so that the slow release rate is uncontrollable, and the polyethylene glycol derivative with the star-shaped macromolecular structure can be effectively inserted among the micromolecule selenate to serve as a barrier to prevent the micromolecule selenate from aggregating to form clusters on one hand; on the other hand, the micromolecule selenate is easy to entangle due to the longer molecular chain, so that the micromolecule selenate is effectively attached to the polyethylene glycol derivatives with the star-shaped macromolecular structure, and when the chitosan microspheres are dissolved in a human body, the polyethylene glycol derivatives with the star-shaped macromolecular structure are gradually dissolved, and free micromolecule selenate is gradually released. Thereby enhancing the slow release effect of the selenate. Therefore, the release rate and encapsulation rate of comparative examples 4 to 5 are also slightly lower than those of example 1, compared to example 1. Solution B of comparative example 6 contained no emulsifier, so that the chitosan was not completely dispersed in the aqueous phase when mixed with selenate and polyvinyl alcohol; the conventional chitosan used in comparative example 7, which has not been hydrophilically modified by carboxymethylation, hydroxyethylation and sulfoation, has limited solubility in water. Thus, comparative examples 6 to 7 all resulted in a decrease in the specific surface area of chitosan, selenate and polyvinyl alcohol contact; therefore, the selenium-loaded chitosan microspheres formed after mixing have the conditions of partial non-uniformity and phase separation, and the release rate and the encapsulation rate of the selenium-loaded chitosan microspheres are obviously influenced.
The above comparison of examples 1-5 with comparative examples 1-7 fully demonstrates the advancement of the presently disclosed solution.
The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention, and various modifications and changes may be made by those skilled in the art. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (8)
1. A preparation method of a selenium-loaded chitosan microsphere with a slow release effect is characterized by comprising the following steps:
s1, dissolving selenate and polyvinyl alcohol in a mixed solution of alcohol and water to form a solution A;
s2, dissolving chitosan in an aqueous solution containing an emulsifier to form a solution B;
s3, dripping the solution B into the solution A, and uniformly stirring to obtain a mixed solution;
s4, adding a cross-linking agent into the mixed solution, stirring at 30-50 ℃, adding a dispersing agent into the mixed solution after a precipitate is formed, and performing ultrasonic treatment to form solid particles;
and S5, after filtering, collecting solid particles, and air-drying to obtain the selenium-loaded chitosan microspheres with the slow release effect.
2. The method for preparing selenium-loaded chitosan microspheres with sustained release effect according to claim 1, wherein the selenate is selected from sodium selenate, potassium selenate or magnesium selenate.
3. The preparation method of the selenium-loaded chitosan microsphere with the slow release effect according to claim 1, wherein the polyvinyl alcohol is modified polyvinyl alcohol, and the specific modification steps are as follows:
(1) blending polyvinyl alcohol and citric acid to form a mixed solution, wherein the citric acid accounts for 0.1-1% of the polyvinyl alcohol;
(2) adding concentrated sulfuric acid into the mixed solution, heating the mixed solution to 90-100 ℃, and reacting for 3-5h to form polyvinyl alcohol containing polyethylene glycol citrate;
(3) the polyvinyl alcohol containing polyethylene glycol citrate was adjusted to pH 7-8 to obtain a modified polyvinyl alcohol.
4. The method for preparing selenium-loaded chitosan microspheres with sustained release effect according to claim 1, wherein the emulsifier is selected from span or tween type emulsifier.
5. The method for preparing the selenium-loaded chitosan microsphere with the slow release effect of claim 1, wherein selenate accounts for 2-5 wt% of chitosan; the polyvinyl alcohol accounts for 5-10 wt% of the chitosan.
6. The method for preparing the selenium-loaded chitosan microsphere with the slow release effect of claim 1, wherein the number average molecular weight of the polyethylene glycol is more than 400.
7. The method for preparing selenium-loaded chitosan microspheres with slow release effect according to claim 1, wherein the cross-linking agent is selected from glyoxal, malondialdehyde, succindialdehyde or glutaraldehyde.
8. The method for preparing selenium-loaded chitosan microspheres with slow release effect according to claim 1, wherein the chitosan is selected from carboxymethylated chitosan, hydroxyethylated chitosan or sulfonated chitosan.
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