CN114224873B - Preparation method of icariin sustained-release nano capsule - Google Patents
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Abstract
The invention discloses a preparation method of icariin sustained-release nano capsules, which comprises the following steps: modifying the hollow mesoporous silica nanoparticles by using isocyanatopropyltriethoxysilane as a modifier to obtain modified hollow mesoporous silica nanoparticles, reacting with beta-cyclodextrin, uniformly mixing a product with icariin and ethanol water solution, performing ultrasonic treatment for 8-15h, centrifuging, washing with alcohol, and drying to obtain icariin microspheres; mixing icariin microsphere, icariin, hesperidin, ginsenoside and sodium dodecyl sulfate, stirring at 30-35 deg.C, adding sodium alginate water solution and glucomannan water solution, stirring at 30-40 deg.C, adding chitosan water solution and nano silicon dioxide anhydrous ethanol dispersion, stirring at 30-40 deg.C, adding glutaraldehyde, solidifying, and drying. The preparation method provided by the invention has the advantages of simple process, uniform particle size distribution of the obtained capsule, good icariin solubility, high bioavailability and excellent sustained release performance.
Description
Technical Field
The invention relates to the technical field of traditional Chinese medicines, in particular to a preparation method of icariin sustained-release nano capsules.
Background
Icariin is an effective active ingredient extracted from epimedium herb, is a flavonoid glycoside compound, has pharmacological activities of resisting tumors, promoting the proliferation and differentiation of bone cells, regulating the immunity of organisms, resisting aging and the like, and attracts the attention of numerous scholars at home and abroad in recent years. Various icariin preparations have been disclosed in the prior art, but icariin is hardly soluble in water, and the existing products have the defects of poor oral absorption, low bioavailability and the like, so that the application of the icariin preparations is limited.
Disclosure of Invention
Based on the technical problems in the background art, the invention provides a preparation method of an icariin sustained-release nanocapsule, the process is simple, the obtained nanocapsule has uniform particle size distribution, the solubility of icariin is changed, the bioavailability of the icariin is improved, and meanwhile, the icariin sustained-release nanocapsule is long in release time and excellent in sustained-release performance.
The invention provides a preparation method of icariin sustained-release nano capsules, which comprises the following steps:
s1, modifying hollow mesoporous silica nanoparticles by using isocyanatopropyl triethoxysilane as a modifier to obtain modified hollow mesoporous silica nanoparticles;
s2, reacting the modified hollow mesoporous silica nanoparticles with beta-cyclodextrin to obtain modified silica;
s3, uniformly mixing the modified silicon dioxide, icariin and an ethanol water solution, performing ultrasonic treatment for 8-15 hours, centrifuging, washing with alcohol, and drying to obtain icariin microspheres;
s4, mixing icariin microspheres, icariin, hesperidin, ginsenoside and sodium dodecyl sulfate, stirring uniformly at 30-35 ℃, adding a sodium alginate aqueous solution and a glucomannan aqueous solution, stirring uniformly at 30-40 ℃, adding a chitosan aqueous solution and a nano-silica absolute ethyl alcohol dispersion, continuously stirring uniformly at 30-40 ℃, adding glutaraldehyde for curing, and drying to obtain the icariin sustained-release nano-capsule.
Preferably, S1 specifically comprises the following steps: uniformly mixing the hollow mesoporous silica nanoparticles with absolute ethyl alcohol, adding isocyanatopropyl triethoxysilane, stirring at 70-78 ℃ in the dark for 15-20h, filtering and drying to obtain the modified hollow mesoporous silica nanoparticles.
Preferably, the weight ratio of the hollow mesoporous silica nanoparticles to the isopropyltriethoxysilane is 6-10:20-25.
Preferably, the specific process of S2 includes the following steps: mixing beta-cyclodextrin and DMF, heating to 70-85 ℃, adding the modified hollow mesoporous silica nanoparticles, reacting for 5-10h under the protection of nitrogen at 70-85 ℃, and after the reaction is finished, centrifugally separating, washing and drying to obtain the modified silica.
Preferably, the weight ratio of the beta-cyclodextrin to the modified hollow mesoporous silica nanoparticles is 3-6:1.
preferably, in S3, the weight ratio of the modified silica to the icariin is 1:1-6.
Preferably, in S4, the weight ratio of the icariin microspheres, icariin, hesperidin and ginsenoside is 5-15:3-9:1-8:2-10.
Preferably, in S4, the weight of the sodium alginate, the glucomannan, the chitosan and the nano silicon dioxide is respectively 0.5 to 0.8 time, 0.1 to 0.3 time, 0.2 to 1 time and 0.1 to 0.4 time of that of the icariin microspheres.
Preferably, the particle size of the hollow mesoporous silica nanoparticles is 400-600nm.
Preferably, in the specific process of S2, the washing may include dimethylsulfoxide washing and deionized water washing; the drying can be vacuum drying at 65-75 deg.C for 5-12h.
Preferably, the mass concentration of the sodium alginate aqueous solution can be 1.5-2.3%; the mass concentration of the glucomannan aqueous solution can be 1-1.5%; the mass concentration of the chitosan aqueous solution can be 0.6-0.86%; the mass concentration of the nano silicon dioxide absolute ethyl alcohol dispersion liquid can be 0.5-1.2%; the glutaraldehyde is a glutaraldehyde solution, and the mass concentration of the glutaraldehyde solution is 2%.
In the preparation method of the icariin sustained-release nanocapsule, firstly, the hollow mesoporous silica nanoparticle is modified by taking isocyanatopropyl triethoxysilane as a modifier to obtain a modified hollow mesoporous silica nanoparticle, isocyanate groups are introduced into molecules and can react with hydroxyl groups in beta-cyclodextrin after being mixed with the beta-cyclodextrin, so that the cyclodextrin is introduced into the molecules, the obtained modified silica simultaneously contains mesoporous silica with adsorption and cyclodextrin with inclusion, icariin is mixed with icariin to obtain icariin microspheres with high drug loading amount, and then the icariin microspheres, icariin, hesperidin and ginsenoside are taken as nucleants, sodium alginate, glucomannan, chitosan and nano-silicon dioxide are taken as film forming materials, glutaraldehyde is added for solidification to obtain the icariin sustained-release nano-capsule, the modern nano-technology is applied to nanocrystallize insoluble drugs, the solubility and the dispersibility of icariin are greatly improved, the solubility of the icariin in water is improved, the absorption rate of the icariin is improved, meanwhile, the particle size of the icariin is uniformly distributed and is between 200 and 300nm, the icariin has a core-shell structure, a shell of the icariin adopts a special film forming substance, the strength is high, the stability is good, the encapsulation performance of the icariin is excellent, the icariin adopts two different coating modes, the drug release time is long, the release and the utilization of the icariin the gastrointestinal tract are facilitated, and the utilization rate of the icariin is improved; the hesperidin and ginsenoside are added to cooperate with icariin, so that the medicine effect is good.
Detailed Description
The technical solution of the present invention will be described in detail below with reference to specific examples.
Example 1
The invention provides a preparation method of icariin sustained-release nano capsules, which comprises the following steps:
s1, uniformly mixing hollow mesoporous silica nanoparticles with absolute ethyl alcohol, and adding isocyanatopropyl triethoxysilane, wherein the weight ratio of the hollow mesoporous silica nanoparticles to the isocyanatopropyl triethoxysilane is 10:23, stirring for 20 hours at 70 ℃ in the dark, filtering and drying to obtain modified hollow mesoporous silica nanoparticles;
s2, mixing beta-cyclodextrin and DMF, heating to 70 ℃, and adding the modified hollow mesoporous silica nanoparticles, wherein the weight ratio of the beta-cyclodextrin to the modified hollow mesoporous silica nanoparticles is 6:1, reacting for 5 hours under the protection of nitrogen at 70 ℃, and after the reaction is finished, centrifugally separating, washing and drying to obtain modified silicon dioxide;
s3, uniformly mixing the modified silicon dioxide, icariin and an ethanol water solution, performing ultrasonic treatment for 8 hours, centrifuging, washing with alcohol, and drying to obtain icariin microspheres; wherein the weight ratio of the modified silicon dioxide to the icariin is 1:1;
s4, mixing icariin microspheres, icariin, hesperidin, ginsenoside and sodium dodecyl sulfate, wherein the weight ratio of the icariin microspheres, icariin, hesperidin and ginsenoside is 5:9:8:2, uniformly stirring at 35 ℃, adding a sodium alginate aqueous solution and a glucomannan aqueous solution, uniformly stirring at 30 ℃, adding a chitosan aqueous solution and a nano-silica absolute ethyl alcohol dispersion, continuously stirring at 30 ℃ until the mixture is uniform, adding glutaraldehyde for curing, and drying to obtain the icariin sustained-release nano-capsules; wherein the weight of the sodium alginate, the glucomannan, the chitosan and the nano silicon dioxide is respectively 0.5 time, 0.3 time, 0.2 time and 0.4 time of that of the icariin microspheres.
Example 2
The invention provides a preparation method of icariin sustained-release nano capsules, which comprises the following steps:
s1, uniformly mixing hollow mesoporous silica nanoparticles with absolute ethyl alcohol, and adding isocyanatopropyl triethoxysilane, wherein the weight ratio of the hollow mesoporous silica nanoparticles to the isocyanatopropyl triethoxysilane is 7:23, stirring for 17 hours at 73 ℃ in the dark, filtering and drying to obtain modified hollow mesoporous silica nanoparticles; wherein the particle size of the hollow mesoporous silica nanoparticle is 400-600nm;
s2, mixing beta-cyclodextrin and DMF, heating to 76 ℃, and adding the modified hollow mesoporous silica nanoparticles, wherein the weight ratio of the beta-cyclodextrin to the modified hollow mesoporous silica nanoparticles is 4:1, reacting for 8 hours under the protection of nitrogen at 76 ℃, and after the reaction is finished, centrifugally separating, washing and drying to obtain modified silicon dioxide;
s3, uniformly mixing the modified silicon dioxide, icariin and an ethanol water solution, performing ultrasonic treatment for 9 hours, centrifuging, washing with alcohol, and drying to obtain icariin microspheres; wherein the weight ratio of the modified silicon dioxide to the icariin is 1:3;
s4, mixing icariin microspheres, icariin, hesperidin, ginsenoside and sodium dodecyl sulfate, wherein the weight ratio of the icariin microspheres, icariin, hesperidin and ginsenoside is 11:7:3:7, uniformly stirring at 35 ℃, adding a sodium alginate aqueous solution and a glucomannan aqueous solution, uniformly stirring at 35 ℃, adding a chitosan aqueous solution and a nano-silica absolute ethyl alcohol dispersion, continuously stirring at 35 ℃ until the mixture is uniform, adding glutaraldehyde for curing, and drying to obtain the icariin sustained-release nano-capsules; wherein the weight of the sodium alginate, the glucomannan, the chitosan and the nano silicon dioxide is respectively 0.5 time, 0.1 time, 0.2 time and 0.3 time of that of the icariin microspheres.
Example 3
The invention provides a preparation method of icariin sustained-release nano capsules, which comprises the following steps:
s1, uniformly mixing hollow mesoporous silica nanoparticles with absolute ethyl alcohol, and adding isocyanatopropyl triethoxysilane, wherein the weight ratio of the hollow mesoporous silica nanoparticles to the isocyanatopropyl triethoxysilane is 7:20, stirring for 15 hours at 75 ℃ in the dark, filtering and drying to obtain modified hollow mesoporous silica nanoparticles;
s2, mixing beta-cyclodextrin and DMF, heating to 85 ℃, and adding the modified hollow mesoporous silica nanoparticles, wherein the weight ratio of the beta-cyclodextrin to the modified hollow mesoporous silica nanoparticles is 3:1, reacting for 10 hours under the protection of nitrogen at 85 ℃, and after the reaction is finished, centrifugally separating, washing and drying to obtain modified silicon dioxide;
s3, uniformly mixing the modified silicon dioxide, icariin and an ethanol water solution, performing ultrasonic treatment for 15 hours, centrifuging, washing with alcohol, and drying to obtain icariin microspheres; wherein the weight ratio of the modified silicon dioxide to the icariin is 1:6;
s4, mixing icariin microspheres, icariin, hesperidin, ginsenoside and sodium dodecyl sulfate, wherein the weight ratio of the icariin microspheres, icariin, hesperidin and ginsenoside is 15:4:3:7, uniformly stirring at 30 ℃, adding a sodium alginate aqueous solution and a glucomannan aqueous solution, uniformly stirring at 40 ℃, adding a chitosan aqueous solution and a nano-silica absolute ethyl alcohol dispersion, continuously stirring at 40 ℃ until the mixture is uniform, adding glutaraldehyde for curing, and drying to obtain the icariin sustained-release nano-capsules; wherein the weight of the sodium alginate, the glucomannan, the chitosan and the nano silicon dioxide is respectively 0.8 time, 0.1 time, 1 time and 0.1 time of that of the icariin microspheres.
Example 4
The invention provides a preparation method of icariin sustained-release nano capsules, which comprises the following steps:
s1, uniformly mixing hollow mesoporous silica nanoparticles with absolute ethyl alcohol, and adding isocyanatopropyl triethoxysilane, wherein the weight ratio of the hollow mesoporous silica nanoparticles to the isocyanatopropyl triethoxysilane is 6:25, stirring for 18 hours at 78 ℃ in the dark, filtering and drying to obtain modified hollow mesoporous silica nanoparticles; the particle size of the hollow mesoporous silica nanoparticle is 400-600nm;
s2, mixing beta-cyclodextrin and DMF, heating to 80 ℃, and adding the modified hollow mesoporous silica nanoparticles, wherein the weight ratio of the beta-cyclodextrin to the modified hollow mesoporous silica nanoparticles is 4:1, reacting for 8 hours under the protection of nitrogen at 80 ℃, and after the reaction is finished, centrifugally separating, washing and drying to obtain modified silicon dioxide;
s3, uniformly mixing the modified silicon dioxide, icariin and an ethanol water solution, performing ultrasonic treatment for 13 hours, centrifuging, washing with alcohol, and drying to obtain icariin microspheres; wherein the weight ratio of the modified silicon dioxide to the icariin is 1:4;
s4, mixing icariin microspheres, icariin, hesperidin and ginsenoside with sodium dodecyl sulfate, wherein the weight ratio of the icariin microspheres, the icariin, the hesperidin and the ginsenoside is 7:3:1:10; stirring uniformly at 32 ℃, adding a sodium alginate aqueous solution and a glucomannan aqueous solution, stirring uniformly at 32 ℃, adding a chitosan aqueous solution and a nano-silica absolute ethyl alcohol dispersion, stirring uniformly at 32 ℃, adding glutaraldehyde for curing, and drying to obtain the icariin sustained-release nano-capsules; wherein the weight of the sodium alginate, the glucomannan, the chitosan and the nano silicon dioxide is respectively 0.5 time, 0.2 time, 0.3 time and 0.3 time of that of the icariin microspheres.
Example 5
The invention provides a preparation method of icariin sustained-release nano capsules, which comprises the following steps:
s1, uniformly mixing hollow mesoporous silica nanoparticles with absolute ethyl alcohol, and adding isocyanatopropyl triethoxysilane, wherein the weight ratio of the hollow mesoporous silica nanoparticles to the isocyanatopropyl triethoxysilane is 7:24, stirring for 17 hours at 73 ℃ in the dark, filtering and drying to obtain modified hollow mesoporous silica nanoparticles; wherein the particle size of the hollow mesoporous silica nanoparticles is 400-600nm;
s2, mixing beta-cyclodextrin and DMF, heating to 75 ℃, and adding the modified hollow mesoporous silica nanoparticles, wherein the weight ratio of the beta-cyclodextrin to the modified hollow mesoporous silica nanoparticles is 5:1, reacting for 7 hours under the protection of nitrogen at 75 ℃, and after the reaction is finished, centrifugally separating, washing and drying to obtain modified silicon dioxide;
s3, uniformly mixing the modified silicon dioxide, icariin and an ethanol water solution, performing ultrasonic treatment for 9 hours, centrifuging, washing with alcohol, and drying to obtain icariin microspheres; wherein the weight ratio of the modified silicon dioxide to the icariin is 1:3;
s4, mixing icariin microspheres, icariin, hesperidin, ginsenoside and sodium dodecyl sulfate, wherein the weight ratio of the icariin microspheres, icariin, hesperidin and ginsenoside is 11:5:6:7; stirring uniformly at 34 ℃, adding a sodium alginate aqueous solution and a glucomannan aqueous solution, stirring uniformly at 34 ℃, adding a chitosan aqueous solution and a nano-silica absolute ethyl alcohol dispersion, stirring uniformly at 34 ℃, adding glutaraldehyde for curing, and drying to obtain the icariin sustained-release nano-capsules; wherein the weight of the sodium alginate, the glucomannan, the chitosan and the nano silicon dioxide is respectively 0.7 time, 0.1 time, 0.7 time and 0.1 time of that of the icariin microspheres.
Example 6
The invention provides a preparation method of icariin sustained-release nano capsules, which comprises the following steps:
s1, uniformly mixing hollow mesoporous silica nanoparticles with absolute ethyl alcohol, and adding isocyanatopropyl triethoxysilane, wherein the weight ratio of the hollow mesoporous silica nanoparticles to the isocyanatopropyl triethoxysilane is 8:23, stirring for 15 hours at 75 ℃ in the dark, filtering and drying to obtain modified hollow mesoporous silica nanoparticles;
s2, mixing beta-cyclodextrin and DMF, heating to 80 ℃, and adding the modified hollow mesoporous silica nanoparticles, wherein the weight ratio of the beta-cyclodextrin to the modified hollow mesoporous silica nanoparticles is 5:1, reacting for 6 hours under the conditions of nitrogen protection and 80 ℃, and after the reaction is finished, centrifugally separating, washing and drying to obtain modified silicon dioxide;
s3, uniformly mixing the modified silicon dioxide, icariin and an ethanol water solution, performing ultrasonic treatment for 12 hours, centrifuging, washing with alcohol, and drying to obtain icariin microspheres; wherein the weight ratio of the modified silicon dioxide to the icariin is 1:5;
s4, mixing icariin microspheres, icariin, hesperidin, ginsenoside and sodium dodecyl sulfate, wherein the weight ratio of the icariin microspheres, icariin, hesperidin and ginsenoside is 11:5:7:5; stirring uniformly at 35 ℃, adding a sodium alginate aqueous solution and a glucomannan aqueous solution, stirring uniformly at 35 ℃, adding a chitosan aqueous solution and a nano silicon dioxide absolute ethyl alcohol dispersion solution, continuously stirring uniformly at 35 ℃, adding glutaraldehyde for curing, and drying to obtain the icariin sustained-release nano capsule; wherein the weight of the sodium alginate, the glucomannan, the chitosan and the nano silicon dioxide is respectively 0.5 time, 0.15 time, 0.4 time and 0.1 time of that of the icariin microspheres.
The nanocapsules prepared in examples 1 to 6 of the present invention were placed in an oven at a temperature of 50 ℃ and a refrigerator at-18 ℃ and observed for cold and hot stability after 30 days; the results show that the nanocapsules prepared in examples 1 to 6 were intact in appearance and free from oil precipitation.
Grinding the nanocapsules prepared in examples 1-6 into powder, accurately weighing a certain amount of powder product, soaking the powder product in hydrochloric acid solution with the temperature of 37 ℃ and the pH value of 1 for 6 hours, taking supernatant, volatilizing and drying at 80 ℃, adding into anhydrous methanol, fixing the volume in a 100ml volumetric flask, measuring the absorbance at 270nm by using an ultraviolet spectrophotometer by taking the anhydrous methanol as a contrast phase, calculating the concentration and the content of icariin, and calculating the drug loading rate and the encapsulation rate; the calculation shows that the content of icariin in the nano-capsules prepared in the examples 1-6 is more than or equal to 43mg/g, the drug loading is high, and the encapsulation rate is more than or equal to 78.9%.
The nanocapsules prepared in examples 1 to 6 were placed in a dialysis bag, placed in a beaker containing 100ml of phosphate buffer solution (pH = 7.2), and drug release was carried out at 37 ℃ and 100 r/min. Taking out 5ml of solution from a beaker at regular intervals, immediately supplementing fresh phosphate buffer solution with the same amount of pH =7.2, drying the taken out 5ml of sample solution at 80 ℃, dissolving the sample solution by using anhydrous methanol, fixing the volume in a 100ml volumetric flask, then taking a proper amount of the sample solution in a cuvette, measuring the absorbance at 270nm by using the anhydrous methanol as a comparison phase and using an ultraviolet spectrophotometer to calculate the concentration and the content of the sample solution, wherein the 24-hour accumulated release amount reaches more than 69 percent and can be slowly released for more than 11 days.
The above description is only for the preferred embodiment of the present invention, but the scope of the present invention is not limited thereto, and any person skilled in the art should be considered to be within the technical scope of the present invention, and the technical solutions and the inventive concepts thereof according to the present invention should be equivalent or changed within the scope of the present invention.
Claims (9)
1. A preparation method of icariin sustained-release nano capsules is characterized by comprising the following steps:
s1, modifying hollow mesoporous silica nanoparticles by using isocyanatopropyl triethoxysilane as a modifier to obtain modified hollow mesoporous silica nanoparticles;
s2, reacting the modified hollow mesoporous silica nanoparticles with beta-cyclodextrin to obtain modified silica;
s3, uniformly mixing the modified silicon dioxide, icariin and an ethanol water solution, performing ultrasonic treatment for 8-15 hours, centrifuging, washing with alcohol, and drying to obtain icariin microspheres;
s4, mixing icariin microspheres, icariin, hesperidin, ginsenoside and sodium dodecyl sulfate, stirring uniformly at 30-35 ℃, adding a sodium alginate aqueous solution and a glucomannan aqueous solution, stirring uniformly at 30-40 ℃, adding a chitosan aqueous solution and a nano-silica absolute ethyl alcohol dispersion, continuously stirring uniformly at 30-40 ℃, adding glutaraldehyde for curing, and drying to obtain the icariin sustained-release nano-capsule.
2. The preparation method of the icariin sustained-release nanocapsule according to claim 1, wherein the S1 specifically comprises the following steps: the hollow mesoporous silica nanoparticles and absolute ethyl alcohol are uniformly mixed, isopropyl triethoxysilane isocyanate is added, the mixture is stirred for 15 to 20 hours at the temperature of between 70 and 78 ℃ in the dark, and the modified hollow mesoporous silica nanoparticles are obtained after filtration and drying.
3. The preparation method of icariin sustained-release nanocapsules according to claim 1 or 2, wherein the weight ratio of the hollow mesoporous silica nanoparticles to the isopropyltriethoxysilane isocyanate is 6-10:20-25.
4. The preparation method of the icariin sustained-release nanocapsule according to claim 1 or 2, wherein the specific process of S2 comprises the steps of: mixing beta-cyclodextrin and DMF, heating to 70-85 ℃, adding the modified hollow mesoporous silica nanoparticles, reacting for 5-10h under the conditions of nitrogen protection and 70-85 ℃, and after the reaction is finished, performing centrifugal separation, washing and drying to obtain the modified silica.
5. The preparation method of the icariin sustained-release nanocapsule according to claim 1 or 2, wherein the weight ratio of the beta-cyclodextrin to the modified hollow mesoporous silica nanoparticles is 3-6:1.
6. the method for preparing the icariin sustained-release nanocapsule according to claim 1 or 2, wherein in S3, the weight ratio of the modified silicon dioxide to the icariin is 1:1-6.
7. The preparation method of the icariin sustained-release nanocapsule according to claim 1 or 2, wherein in S4, the weight ratio of the icariin microspheres, icariin, hesperidin, ginsenoside is 5-15:3-9:1-8:2-10.
8. The method for preparing the icariin sustained-release nanocapsule according to claim 1 or 2, wherein the weight of the sodium alginate, the glucomannan, the chitosan and the nano-silica used in S4 is 0.5 to 0.8 times, 0.1 to 0.3 times, 0.2 to 1 times and 0.1 to 0.4 times of the weight of the icariin microsphere, respectively.
9. The preparation method of the icariin sustained-release nanocapsule according to claim 1 or 2, wherein the particle size of the hollow mesoporous silica nanoparticles is 400-600nm.
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| CN107496383A (en) * | 2017-10-13 | 2017-12-22 | 遵义医学院 | A kind of icariin sustained and controlled release nanoparticle and preparation method thereof |
| CN109718221A (en) * | 2017-10-31 | 2019-05-07 | 鲁南制药集团股份有限公司 | A kind of epimedium aglucone preparation |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN107496383A (en) * | 2017-10-13 | 2017-12-22 | 遵义医学院 | A kind of icariin sustained and controlled release nanoparticle and preparation method thereof |
| CN109718221A (en) * | 2017-10-31 | 2019-05-07 | 鲁南制药集团股份有限公司 | A kind of epimedium aglucone preparation |
Non-Patent Citations (1)
| Title |
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| Multi-Functional Silica-Based Mesoporous Materials for Simultaneous Delivery of Biologically Active Ions and Therapeutic Biomolecules;Hui Zhu等;《Acta Biomaterialia》;20210516;第1-55页 * |
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