LU500813B1 - Asiaticoside-chitosan-sodium Alginate Microsphere and Preparation Method and Application thereof - Google Patents
Asiaticoside-chitosan-sodium Alginate Microsphere and Preparation Method and Application thereof Download PDFInfo
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Abstract
The invention discloses asiaticoside-chitosan-sodium alginate microspheres, preparation method and application thereof, belonging to the technical field of biomedical materials. The microsphere is prepared by adopting an emulsification cross-linking method and finally freeze-drying, and the preparation method comprises the following steps: 1) preparing sodium alginate solution and asiaticoside-chitosan acetic acid solution respectively; 2) slowly and uniformly dripping sodium alginate solution into the oil phase, and stirring at high speed to form colostrum; 3) the asiaticoside-chitosan acetic acid solution is slowly and evenly dripped into colostrum, stirred and fully emulsified; and 4) slowly and uniformly dripping glyceraldehyde solution for crosslinking and curing, centrifuging, washing the precipitate with petroleum ether and absolute ethanol in turn, and vacuum freeze-drying to obtain the pale yellow powder of asiaticoside-sodium alginate-chitosan microspheres.
Description
DESCRIPTION LU500813 Asiaticoside-chitosan-sodium Alginate Microsphere and Preparation Method and Application thereof
TECHNICAL FIELD The invention relates to the technical field of biomedical materials, in particular to asiaticoside-chitosan-sodium alginate microspheres, preparation method and application thereof.
BACKGROUND Asiaticoside (AS), a triterpenoid saponin compound, is the main active ingredient of Centella asiatica, which has excellent effects in promoting wound healing and resisting hypertrophic scar. In addition, the researchers found that asiaticoside can inhibit the generation of arthritis in mice through collagen-induced arthritis experiments. The specific mechanism may be to inhibit the proliferation of lymphocytes by inhibiting the expression of COX-2 and reducing the expression and release of inflammatory factors such as IL-6 and TNF-a, thus inhibiting the occurrence of immune response. Researchers found that asiaticoside can inhibit the expression and secretion of inflammatory factors such as MPO by inhibiting the expression of COX-2, and promote the expression and activity of inflammatory protective factors such as HO-1, thus inhibiting the occurrence of inflammatory reaction. At the same time, asiaticoside can also inhibit the accumulation of PGE2 as a heating medium, so as to inhibit the inflammation caused by fever induced by lipopolysaccharide in rats. In addition, previous studies have shown that asiaticoside can promote the proliferation of fibroblasts and the synthesis of extracellular matrix during wound healing, increase the content of hydroxyproline, improve the growth of epidermis, collagen and skin, and promote angiogenesis of chick embryonic chorionic urea capsule model. Based on the above researches, AS is currently used in the prevention and treatment of chronic inflammation and the diseases caused by it, especially for the prevention and treatment of allergic diseases, abnormal skin pigmentation, excessive formation of skin blood vessels or inflammatory laceration, and the regulation of the homeostasis of skin tissues.
Chitosan (CS) is a polycationic polysaccharide containing a large number of HUS008TS amino groups obtained by deacetylation of chitin, which has good biocompatibility, innocuity and biodegradability. Sodium alginate (SA) is a polyanionic polysaccharide containing carboxyl group extracted from marine algae, which has good biological viscosity and biodegradability. The amino group of chitosan and carboxyl group of sodium alginate are attracted by positive and negative charges to form polyelectrolyte complex, which has hemostatic, anti-inflammatory and wound healing effects. The sodium alginate-chitosan microsphere is a new type of preparation with slow-release effect, which can achieve the purpose of slow-release and prolonged drug effect by controlling the drug release speed, at the same time, it protects the drug from enzyme degradation and plays a role in improving the bioavailability of the drug, and drugs with low therapeutic index, poor water solubility and unstable properties can also be included in it, so as to concentrate the drugs in the target area, enhance the curative effect and reduce the toxic and side effects. However, the application of microspheres prepared by traditional emulsion crosslinking method is limited due to the use of glutaraldehyde and other toxic crosslinking agents. If AS can use natural sodium alginate-chitosan microspheres as carrier and non-toxic glyceraldehyde as a new cross-linking agent, it is expected to reduce the toxicity of microspheres, realize its continuous administration to lesions, achieve synergistic curative effect, and reduce the pain of patients caused by repeated administration due to sudden release of drugs, thus reducing adverse drug reactions.
SUMMARY The invention provides a preparation method of asiaticoside-chitosan-sodium alginate microspheres aiming at the low bioavailability of asiaticoside and the defects of the preparation method of microspheres at present, that is, the toxicity of microspheres caused by using toxic crosslinking agents such as glutaraldehyde. According to the invention, AS is coated by sodium alginate-chitosan microspheres, and asiaticoside-sodium alginate-chitosan microspheres are prepared by an emulsification cross-linking method, so AS to integrate the performance advantages of as and sodium alginate-chitosan, and provide a certain method basis for proposing 7500879 a new dosage form of AS.
To achieve the above purpose, the present invention provides the following scheme: The invention provides a preparation method of asiaticoside-chitosan-sodium alginate microspheres, which comprises the following steps: preparing asiaticoside-chitosan-sodium alginate microspheres by an emulsification cross-linking method, and freeze-drying.
As a further improvement of the invention, the preparation method specifically comprises the following steps: (a) adding chitosan into glacial acetic acid solution with a volume fraction of 1-3% to dissolve the chitosan and prepare chitosan acetic acid solution; dissolving asiaticoside with absolute ethanol to obtain asiaticoside solution; mixing chitosan aqueous solution and asiaticoside solution, stirring, adding anhydrous calcium chloride after ethanol volatilization, and obtaining asiaticoside-chitosan acetic acid solution containing calcium chloride; (b) dissolving sodium alginate with purified water to prepare sodium alginate aqueous solution; adding the prepared sodium alginate solution slowly and uniformly into the oil phase (mixed solution of 29.25 ml liquid paraffin and 0.75 ml Span80), and stirring at 500-800 rpm for 20-40 min to form colostrum; (c) slowly and uniformly dripping the asiaticoside-chitosan acetic acid solution containing calcium chloride into the colostrum formed in step (b), stirring and fully emulsifying to form emulsion; and (d) slowly and uniformly dripping glyceraldehyde solution into the emulsion obtained in step (c) (adding 1 ml takes about 5 minutes), after cross-linking and curing, centrifuging, removing supernatant, washing precipitates with petroleum ether and absolute ethanol in turn, and vacuum freeze-drying to obtain the pale yellow powder of asiaticoside-sodium alginate-chitosan microspheres.
As a further improvement of the invention, in step (a), the volume fraction of HUS008TS glacial acetic acid aqueous solution is 2%, the mass ratio of anhydrous calcium chloride to chitosan is 4: 1, and the mass ratio of chitosan to asiaticoside is 1:0.2-0.6.
As a further improvement of the invention, the volume ratio of sodium alginate to oil phase in step (b) is 1: 6.
As a further improvement of the invention, in step (c), the volume ratio of asiaticoside-chitosan acetic acid solution containing calcium chloride to colostrum is
1.7.
As a further improvement of the invention, the volume ratio of glyceraldehyde in step (d) to the emulsion obtained in step (c) is 1: 40.
As a further improvement of the invention, the molecular weight of the chitosan is 300-400 kDa and the degree of deacetylation is 90%.
The invention also provides an asiaticoside-chitosan-sodium alginate microsphere prepared by the preparation method of the asiaticoside-chitosan-sodium alginate microsphere.
The invention also provides the application of the asiaticoside-chitosan-sodium alginate microsphere as a wound healing material.
The invention discloses the following technical effect: (1) The asiaticoside-chitosan-sodium alginate microspheres prepared by the invention have good sustained-release effect; (2) The mild and nontoxic crosslinking agent is adopted, which not only makes the material non-toxic and safe, but also improves the uniformity, and has high drug loading and encapsulation efficiency; (3) The asiaticoside-chitosan-sodium alginate microspheres prepared by the invention are small and uniform, have small adhesion degree, high roundness and narrow particle size range, the laser particle size analyzer is used to measure the particle size range, the wet dispersion technology is used, the mechanical stirring is used to disperse the microspheres evenly in the water phase, the ultrasonic high-frequency oscillation is used to fully disperse the agglomerated microspheres, and the electromagnetic circulating pump is used to uniformly distribute the microspheres in the whole circulation system. The test results show that: most of the 7500879 microspheres are distributed in the range of 3.122-4.366 um, Dıo=3.122 um, Dso=3.819 um, Doo=4.366 um, Sp=0.326; (4) The asiaticoside-chitosan-sodium alginate microspheres prepared by the invention have high drug loading and encapsulation efficiency; (5) The asiaticoside-chitosan-sodium alginate microspheres prepared by the invention have good biocompatibility and are biodegradable; (6) The preparation process of asiaticoside-chitosan-sodium alginate microspheres prepared by the invention is mild in reaction conditions, simple in operation, easy to obtain microspheres with round appearance, high in yield and easy for industrial production.
BRIEF DESCRIPTION OF THE FIGURES In order to explain the embodiment of the present invention or the technical scheme in the prior art more clearly, the following will briefly introduce the drawings used in the embodiment. Obviously, the drawings in the following description are only some embodiments of the present invention, and for those of ordinary skill in the art, other drawings can be obtained according to these drawings without paying creative labor.
Fig. 1 is a particle size distribution diagram of microspheres prepared in example L; Fig. 2 is an electron micrograph of microspheres prepared in Example 1-an electron micrograph of microspheres magnified by 5 k times; Fig. 3 is an electron micrograph of microspheres prepared in Example 1-an electron micrograph of microspheres magnified by 10 k times; Fig. 4 is a time-release curve of microspheres prepared in example 1; Fig. 5 is a time-cumulative release percentage curve of microspheres prepared in example 1.
DESCRIPTION OF THE INVENTION The following is a detailed description of various exemplary embodiments of the present invention, which should not be regarded as a limitation of the present invention, but should be understood as a more detailed description of certain aspects, HUS008TS characteristics and embodiments of the present invention.
It should be understood that the terms described in the present invention are only for describing specific embodiments, and are not intended to limit the present invention. In addition, as for the numerical range in the present invention, it should be understood that every intermediate value between the upper limit and the lower limit of the range is also specifically disclosed. Intermediate values within any stated value or stated range and every smaller range between any other stated value or intermediate values within the stated range are also included in the present invention. The upper and lower limits of these smaller ranges can be independently included or excluded from the range.
Unless otherwise stated, all technical and scientific terms used herein have the same meanings as commonly understood by those skilled in the art to which this invention relates. Although the present invention only describes preferred methods and materials, any methods and materials similar or equivalent to those described herein may be used in the practice or testing of the present invention. All documents mentioned in this specification are incorporated by reference to disclose and describe methods and/or materials related to the documents. In case of conflict with any incorporated documents, the contents of this specification shall prevail.
Without departing from the scope or spirit of the invention, it is obvious to those skilled in the art that many modifications and changes can be made to the specific embodiments of the specification of the invention. Other embodiments derived from the description of the present invention will be apparent to the skilled person. The specification and embodiment of that present invention are merely exemplary.
As used herein, "including", "comprising", "having", "containing", etc. are all open terms, which means including but not limited to.
The sodium alginate is food grade or medical grade, and its molecular weight is 100 kDa. The molecular weight of chitosan is 300-400 kDa and the degree of deacetylation is 90%.
Example 1
(a) Weighing 1 g of chitosan and adding it into 100 mL of glacial acetic acid HUS008TS solution with a volume fraction of 2% to dissolve the chitosan to prepare chitosan acetic acid solution; 0.6 g of asiaticoside is dissolved in absolute ethanol to obtain asiaticoside solution; mixing the above two solutions, stirring, adding 2 g anhydrous calcium chloride until ethanol is volatilized completely, and obtaining asiaticoside-chitosan acetic acid solution containing calcium chloride; dissolving 1 g of sodium alginate with purified water to prepare sodium alginate aqueous solution; (b) Slowly and uniformly dripping the prepared sodium alginate solution into the oil phase, and stirring at 800 rpm for 30 min minutes to form colostrum; (c) Slowly and uniformly dripping the asiaticoside-chitosan acetic acid solution containing calcium chloride into colostrum, stirring at a high speed of 1000 rpm, and fully emulsifying for 1 hour; and (d) slowly and uniformly dripping 1 mL of glyceraldehyde solution, crosslinking and curing for 1 h, centrifuging at 1000 rpm for 10 min, removing supernatant, washing the precipitate twice with petroleum ether and once with absolute ethanol, and vacuum freeze-drying to obtain the pale yellow powder of asiaticoside-sodium alginate-chitosan microspheres.
Example 2 (a) Weighing 1 g of chitosan and adding it into 100 mL of glacial acetic acid solution with a volume fraction of 1% to dissolve the chitosan to prepare chitosan acetic acid solution; 0.4 g of asiaticoside is dissolved in absolute ethanol to obtain asiaticoside solution; mixing the above two solutions, stirring, adding 2 g anhydrous calcium chloride until ethanol is volatilized completely, and obtaining asiaticoside-chitosan acetic acid solution containing calcium chloride; dissolving 1 g of sodium alginate with purified water to prepare sodium alginate aqueous solution; (b) Slowly and uniformly dripping the prepared sodium alginate solution into the oil phase, and stirring at S00 rpm for 40 min minutes to form colostrum; (c) Slowly and uniformly dripping the asiaticoside-chitosan acetic acid solution containing calcium chloride into colostrum, stirring at a high speed of 3000 rpm, and fully emulsifying for 1 hour;
and (d) slowly and uniformly dripping 1 mL of glyceraldehyde solution, HUS008TS crosslinking and curing for 1 h, centrifuging at 1000 rpm for 10 min, removing supernatant, washing the precipitate twice with petroleum ether and once with absolute ethanol, and vacuum freeze-drying to obtain the pale yellow powder of asiaticoside-sodium alginate-chitosan microspheres.
Example 3 (a) Weighing 1 g of chitosan and adding it into 100 mL of glacial acetic acid solution with a volume fraction of 3% to dissolve the chitosan to prepare chitosan acetic acid solution; 0.6 g of asiaticoside is dissolved in absolute ethanol to obtain asiaticoside solution; mixing the above two solutions, stirring, adding 2 g anhydrous calcium chloride until ethanol is volatilized completely, and obtaining asiaticoside-chitosan acetic acid solution containing calcium chloride; dissolving 1.5 g of sodium alginate with purified water to prepare sodium alginate aqueous solution; (b) Slowly and uniformly dripping the prepared sodium alginate solution into the oil phase, and stirring at 700 rpm for 20 min minutes to form colostrum; (c) Slowly and uniformly dripping the asiaticoside-chitosan acetic acid solution containing calcium chloride into colostrum, stirring at a high speed of 3000 rpm, and fully emulsifying for 1 hour; and (d) slowly and uniformly dripping 2 mL of glyceraldehyde solution, crosslinking and curing for 1 h, centrifuging at 1000 rpm for 10 min, removing supernatant, washing the precipitate twice with petroleum ether and once with absolute ethanol, and vacuum freeze-drying to obtain the pale yellow powder of asiaticoside-sodium alginate-chitosan microspheres.
Example 4 (a) Weighing 1 g of chitosan and adding it into 100 mL of glacial acetic acid solution with a volume fraction of 2% to dissolve the chitosan to prepare chitosan acetic acid solution; 0.6 g of asiaticoside is dissolved in absolute ethanol to obtain asiaticoside solution; mixing the above two solutions, stirring, adding 2 g anhydrous calcium chloride until ethanol is volatilized completely, and obtaining asiaticoside-chitosan acetic acid solution containing calcium chloride; dissolving 0.5 g 7500879 of sodium alginate with purified water to prepare sodium alginate aqueous solution; (b) Slowly and uniformly dripping the prepared sodium alginate solution into the oil phase, and stirring at 800 rpm for 20 min minutes to form colostrum; (c) Slowly and uniformly dripping the asiaticoside-chitosan acetic acid solution containing calcium chloride into colostrum, stirring at a high speed of 3000 rpm, and fully emulsifying for 1 hour; and (d) slowly and uniformly dripping 1 mL of glyceraldehyde solution, crosslinking and curing for 1 h, centrifuging at 1000 rpm for 10 min, removing supernatant, washing the precipitate twice with petroleum ether and once with absolute ethanol, and vacuum freeze-drying to obtain the pale yellow powder of asiaticoside-sodium alginate-chitosan microspheres.
Accurately weigh 100 mg of asiaticoside-sodium alginate-chitosan microspheres in example 1, add them into 50 mL phosphate buffer solution, place them in a constant temperature water bath at (37+1)°C, and oscillate at a constant speed of 100 r-min, take out 5 mL of the dissolution liquid at 0.5 h, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 12 h, 24 h, 2 d, 3 d, 5 d and 7 d respectively. At the same time, an equal amount of fresh phosphate buffer solution with the same temperature was added, and the supernatant was taken after centrifugation for 5 min at 4000 r-min. Take the supernatant of the dissolution of blank microspheres (sodium alginate-chitosan microspheres) as blank control, the cumulative release amount and percentage of asiaticoside at different time points were calculated.
Cumulative release calculation formula: “= ¥& + 28 Vo (where Mi is the cumulative release amount, C; is the release concentration of asiaticoside at the i-th sampling; V is the volume before the first sampling, which is 50 mL; in this experiment; Ci-1 corresponds to the concentration of asiaticoside at the previous sampling point at time 1; V is the volume of each sample, which is 5 mL in this experiment.)
The formula for calculating cumulative release percentage Q is: Q=M;-the HUS008TS content of asiaticoside contained in system *100%.
It can be seen from fig. 2 and fig. 3 that the microspheres of the present invention have uniform size, small adhesion degree and high roundness. It can be seen from figs. 4 and 5 that the in vitro release of asiaticoside-sodium alginate-chitosan microspheres prepared by the present invention is divided into two stages: burst release and slow release. The release amount of asiaticoside was small in the first 5 h, and a sudden release occurred at 6 h, with the cumulative release percentage reaching (43.79+2.07)%. After that, asiaticoside began to release in vitro at a slow rate, with an average release rate of 0.77% per hour in 7-24 h, a cumulative release rate of (57.65+1.32)% in 24 h, an average release rate of 0.92% per day in 2-7 d and a cumulative release rate of (90.03+0.84)% in 7 d.
The laser particle size analyzer was used to measure the particle size range of the microspheres prepared in the best example, and the wet dispersion technology and mechanical stirring were used to uniformly disperse the microspheres in the water phase. Ultrasonic high-frequency oscillation makes the agglomerated microspheres fully dispersed, and electromagnetic circulating pump makes the microspheres uniformly distributed in the whole circulating system. It can be seen from the results in fig. 1 that the particle sizes of microspheres are mostly distributed between 3.122 and 4.366 um, D10=3.122 um, Dso=3.819 um, Doo=4.366 um, Sp=0.326.
Accurately weigh 50 mg of blank microspheres dried to constant weight, put them in a 10 mL volumetric flask, add 0.6 ml of 5% triton X-100 solution for demulsification, then add 8 mL of methanol solution, shake and shake well, ultrasonic for 3 hours, and soak them for 24 hours after constant volume with methanol to obtain methanol leachate of blank microspheres, the methanol leaching solution of asiaticoside-sodium alginate-chitosan microspheres was obtained by the same operation. The methanol leaching solution of blank microspheres was used as reference solution, and the absorption value of the methanol leaching solution of asiaticoside-sodium alginate-chitosan microspheres was measured at 205 nm. The concentration of AS in asiaticoside-sodium alginate-chitosan microspheres was 7500813 calculated by substituting it into the linear regression equation.
The calculation formula 1s as follows: Drug loading (DL)=[amount of drug in microsphere-weight of microsphere] *100%; Entrapment efficiency (EE)=[amount of drug in microsphere-dosage] *100%; Results: the average drug loading was 12.98%, the average entrapment efficiency was 95.84%, and the corresponding RSD values were 1.54% and 2.23%, respectively.
The above-mentioned embodiments only describe the preferred mode of the invention, and do not limit the scope of the invention. On the premise of not departing from the design spirit of the invention, various modifications and improvements made by ordinary technicians in the field to the technical scheme of the invention shall fall within the protection scope determined by the claims of the invention.
Claims (9)
1. À preparation method of asiaticoside-chitosan-sodium alginate microspheres 1s characterized by comprising the following steps: preparing asiaticoside-chitosan-sodium alginate microspheres by an emulsification cross-linking method, and freeze-drying.
2. The preparation method of asiaticoside-chitosan-sodium alginate microspheres according to claim 1, which is characterized by specifically comprising the following steps: (a) adding chitosan into glacial acetic acid solution with a volume fraction of 1-3% to dissolve the chitosan and prepare chitosan acetic acid solution; dissolving asiaticoside with absolute ethanol to obtain asiaticoside solution; mixing chitosan acetic acid solution and asiaticoside solution, stirring, adding anhydrous calcium chloride after ethanol volatilization, and obtaining asiaticoside-chitosan acetic acid solution containing calcium chloride; (b) dissolving sodium alginate with purified water to prepare sodium alginate aqueous solution; slowly and uniformly dripping the prepared sodium alginate solution into the oil phase, and stirring at a speed of 500-800 rpm for 20-40 min to form colostrum; (c) slowly and uniformly dripping the asiaticoside-chitosan acetic acid solution containing calcium chloride into the colostrum formed in step (b), stirring and fully emulsifying to form emulsion; and (d) uniformly dripping glyceraldehyde solution into the emulsion obtained in the step (c), performing cross-linking and curing, centrifuging, removing supernatant, washing the precipitate with petroleum ether and absolute ethyl alcohol in turn, and vacuum freeze-drying to obtain pale yellow powder of asiaticoside-sodium alginate-chitosan microspheres.
3. The preparation method of asiaticoside-chitosan-sodium alginate microspheres according to claim 2, wherein in step (a), the volume fraction of glacial acetic acid aqueous solution is 2%, the mass ratio of anhydrous calcium chloride to chitosan 1s 4: 1, and the mass ratio of chitosan to asiaticoside is 1:0.2-0.6.
4. The preparation method of asiaticoside-chitosan-sodium alginate microspheres 7500879 according to claim 2, characterized in that the volume ratio of sodium alginate to oil phase in step (b) is 1: 6.
5. The preparation method of asiaticoside-chitosan-sodium alginate microspheres according to claim 2, characterized in that the volume ratio of asiaticoside-chitosan acetic acid solution containing calcium chloride to colostrum in step (c) is 1: 7.
6. The preparation method of asiaticoside-chitosan-sodium alginate microspheres according to claim 2, characterized in that the volume ratio of glyceraldehyde solution in step (d) to emulsion obtained in step (c) is 1:40.
7. The preparation method of asiaticoside-chitosan-sodium alginate microspheres according to claim 2, characterized in that the chitosan has a molecular weight of 300-400 kDa and a degree of deacetylation of 90%.
8. An asiaticoside-chitosan-sodium alginate microsphere prepared by the preparation method of asiaticoside-chitosan-sodium alginate microsphere according to any one of claims 1-7.
9. An application of the asiaticoside-chitosan-sodium alginate microsphere according to claim 8 as a wound healing material.
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| CN115337229A (en) * | 2021-12-07 | 2022-11-15 | 博汇美萃生物工程技术(广东)有限公司 | Preparation method and application of composition for scalp care |
| CN115463052A (en) * | 2022-09-22 | 2022-12-13 | 武汉纺织大学 | Preparation method of polymer microsphere sunscreen composition embedded with organic ultraviolet absorbent and sunscreen agent |
| CN115486510A (en) * | 2022-10-22 | 2022-12-20 | 南通奥凯生物技术开发有限公司 | High-purity feed additive containing sodium diacetate and preparation method thereof |
| CN115414381B (en) * | 2022-11-07 | 2023-03-28 | 西南民族大学 | Composition with scar inhibition and/or wound healing promotion effects and preparation method and application thereof |
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| CN101474157B (en) * | 2009-01-19 | 2010-09-15 | 浙江省医学科学院 | Asiatic acid injectable sustained-release microballoons and preparation method thereof |
| CN102578110B (en) * | 2011-12-23 | 2013-07-31 | 河海大学 | Preparation method of artemisinin slow-release body |
| CN106890143A (en) * | 2015-12-18 | 2017-06-27 | 鄂尔多斯市威蒙医药科技有限公司 | The preparation method of the chitosan nano composite particles of appendix panaxoside and cordycepin |
| CN107396923A (en) * | 2017-06-28 | 2017-11-28 | 禹州市天源生物科技有限公司 | A kind of preparation method of artemisinin slow-release body |
| CN107550752A (en) * | 2017-09-11 | 2018-01-09 | 广州聚注通用技术研究院有限公司 | A kind of crease-resistant eye mask that compacts |
| CN108451925B (en) * | 2018-04-16 | 2020-05-26 | 中南大学 | Hollow sustained-release microsphere for drug loading and preparation method thereof |
| CN109568643B (en) * | 2018-10-21 | 2021-08-31 | 浙江理工大学 | Preparation method and application of berberine-containing antibacterial hemostatic microspheres |
| CN109528692B (en) * | 2018-12-03 | 2020-11-10 | 王丽萍 | Concentrated growth factor slow-release freeze-dried film and preparation method thereof |
| CN111228040B (en) * | 2020-01-08 | 2021-06-25 | 河南亚都实业有限公司 | Absorbable anti-adhesion dressing and preparation method thereof |
| CN112315943B (en) * | 2020-11-19 | 2022-02-25 | 广东海洋大学 | Asiaticoside-chitosan-sodium alginate microspheres, preparation method and application thereof |
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2020
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| Publication number | Publication date |
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| CN112315943B (en) | 2022-02-25 |
| WO2022105301A1 (en) | 2022-05-27 |
| CN112315943A (en) | 2021-02-05 |
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