CN114366717A - Enteric solid dispersion particle based on EGCG nano-particle, preparation method and application thereof - Google Patents
Enteric solid dispersion particle based on EGCG nano-particle, preparation method and application thereof Download PDFInfo
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- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/146—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic macromolecular compounds
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- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
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- B—PERFORMING OPERATIONS; TRANSPORTING
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- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
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- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Abstract
The invention provides an EGCG nanoparticle-based enteric solid dispersion particle, a preparation method and application thereof, and belongs to the technical field of bacterial infection prevention. The EGCG average content of the enteric solid dispersion particles based on the EGCG nano-particles provided by the invention is 67.2%, the EGCG enteric solid dispersion particles can be well applied to resisting infection of haemophilus parasuis, riemerella anatipestifer and pasteurella, and the cure rate of three bacterial diseases is more than 80%. Meanwhile, the enteric solid dispersion particles provided by the invention have obvious stability in a gastric juice environment, but can quickly release the nano EGCG in a small intestine environment, so that the enteric solid dispersion provided by the invention not only enhances the stability of the EGCG and has good slow release performance, but also improves the bioavailability of the EGCG.
Description
Technical Field
The invention belongs to the technical field of bacterial infection prevention, and particularly relates to an EGCG nanoparticle-based enteric solid dispersion particle, a preparation method and application thereof.
Background
Green tea is one of the main chinese teas and is popular, with catechins accounting for about 30% of its dry weight and epigallocatechin gallate (EGCG) which is the highest in catechins accounting for about 50% of the mass of catechins. Research shows that EGCG has various pharmacological activities, wherein the antioxidant activity is the most prominent, belongs to a non-enzymatic antioxidant, has the antioxidant activity which is 20 times of that of vitamin E and 6 times of that of superoxide dismutase, has obvious biological activities of eliminating free radicals in vivo, resisting cancer, resisting inflammation, resisting mutation, resisting aging, improving liver function and the like, and has been widely researched in China, America and other countries for potential anticancer effects.
At present, the antibacterial function of EGCG is also verified by many experimental studies, but the related pathogenic bacteria are generally escherichia coli, gram-positive bacteria, gram-negative bacteria and the like. For example, Liu Bing has disclosed the preventive effect of EGCG on E.coli-induced bladder epithelial infection in the article "study of the preventive and therapeutic effects of Epigallocatechin gallate on E.coli-induced bladder epithelial infection". For example, the invention patent 'application of EGCG in preparing preparation or food for preventing pathogenic bacteria infection' discloses the application of epigallocatechin gallate in preparing preparation or food for preventing gram-positive bacteria and/or gram-negative bacteria infection. However, no report about the related application of EGCG in preventing and treating bacterial diseases of pathogenic bacteria such as haemophilus parasuis, riemerella anatipestifer disease and pasteurella has been found.
Meanwhile, although EGCG has strong antioxidant activity, EGCG is very easy to oxidize and difficult to store and prepare, so that the problems of difficult absorption and poor bioavailability of oral EGCG exist in the prior art.
Disclosure of Invention
The EGCG average content of the enteric solid dispersion particles based on the EGCG nano-particles provided by the invention is 67.2%, the EGCG enteric solid dispersion particles can be well applied to resisting infection of haemophilus parasuis, riemerella anatipestifer and pasteurella, and the cure rate of three bacterial diseases is more than 80%. Meanwhile, the enteric solid dispersion particles provided by the invention have remarkable stability in a gastric juice environment, but can quickly release the nano EGCG in a small intestine environment. Therefore, the enteric solid dispersion particle not only enhances the stability of EGCG and has good slow release performance, but also improves the bioavailability of EGCG.
The invention adopts the following technical scheme to achieve the purpose.
The invention provides an EGCG nanoparticle-based enteric solid dispersion particle, which consists of EGCG nanoparticles and a carrier, wherein the average content of EGCG in the dispersion particle is 67.2%.
The invention also provides a preparation method of the enteric solid dispersion particles, which comprises the following steps: (1) preparing nanoparticles: adding a low-molecular-weight chitosan solution into the EGCG solution, fully stirring, adding a sodium tripolyphosphate solution, continuously stirring, centrifuging, collecting precipitate, and vacuum drying; (2) preparing a carrier: taking a proper amount of enteric acrylic resin, hydroxypropyl methylcellulose acetate succinate and polyethylene glycol 8000 to be uniformly mixed as a carrier; (3) dispersion particles were prepared.
The molecular weight of the low molecular weight chitosan is 2.5-3kDa, the enteric acrylic resin is acrylic resin II, and the CAS number of the hydroxypropyl methyl cellulose acetate succinate is 71138-97-1.
Preferably, the concentration of the low molecular weight chitosan solution in the step (1) is 0.1-0.2%.
Preferably, the concentration of the low molecular weight chitosan solution in the step (1) is 0.15%.
Preferably, in the step (2), the weight ratio of the enteric acrylic resin to the hydroxypropyl methyl cellulose acetate succinate to the polyethylene glycol 8000 is 1:5: 1.
Preferably, the weight ratio of the nanoparticles to the carrier in the step (3) is 1: 0.1-1: 1.
Preferably, the weight ratio of the nanoparticles to the carrier in the step (3) is 1: 0.3.
The invention also provides application of the enteric solid dispersion particles in preparation of medicines for preventing and treating bacterial diseases, wherein pathogenic bacteria of the bacterial diseases are haemophilus parasuis, riemerella anatipestifer or pasteurella.
Preferably, the pathogenic bacteria of the bacterial disease are haemophilus parasuis or pasteurella and the enteric solid dispersion is used in an amount of 20 mg/kg.
Preferably, the pathogenic bacteria of the bacterial disease is riemerella anatipestifer, and the dosage of the enteric solid dispersion is 30 mg/kg.
The invention has the beneficial effects that:
(1) the average content of EGCG in the enteric solid dispersion particles provided by the invention is 67.2%, and the biological activity is strong.
(2) The enteric solid dispersion particles provided by the invention have strong stability in a gastric juice simulation environment, and the content of EGCG is still as high as 99.2% after the enteric solid dispersion particles are placed for 10 days; the enteric solid dispersion particles provided by the invention have a high EGCG in-vitro release speed in a small intestine simulated environment, and the release rate reaches 100% after about 8 hours. The enteric solid dispersion particle provided by the invention has obvious stability in a gastric juice environment, and can quickly release the nano EGCG in a small intestine environment.
(3) The Minimum Inhibitory Concentration (MIC) of the EGCG to clinically separated haemophilus parasuis, Riemerella anatipestifer and Pasteurella is 512 mug/mL, 256 mug/mL and 256 mug/mL respectively, and the EGCG shows better inhibition effect.
(4) The enteric solid dispersion particles provided by the invention can be well applied to resisting infection of haemophilus parasuis, riemerella anatipestifer disease and pasteurella, and the cure rate of three bacterial diseases is up to more than 80%.
Drawings
Fig. 1 is the in vitro cumulative release rate of the EGCG nanoparticle-based enteric solid dispersion particles in example 3 in a small intestine simulated environment at different times.
Detailed Description
The present invention will be described in detail below with reference to specific examples. It should be noted that technical features or combinations of technical features described in the following embodiments should not be considered as being isolated, and they may be combined with each other to achieve better technical effects. The experimental methods used in the following examples are all conventional experimental methods unless otherwise specified, and the reagents used therein are obtained from conventional commercial sources unless otherwise specified.
Example 1 preparation of enteric high stable solid dispersion particles based on EGCG nanoparticles
Dissolving low molecular weight chitosan with 0.15% acetic acid to obtain a low molecular weight chitosan solution with the concentration of 0.15%, then adding 10mL of the 0.15% low molecular weight chitosan solution into 100mL of the 0.05% EGCG solution, fully stirring, then adding 1mL of the 0.02% sodium tripolyphosphate solution, continuing stirring for 3h, then centrifuging the solution under the condition of 10000 Xg for 30min, collecting the precipitate, and drying in vacuum. Wherein the low molecular weight chitosan has a molecular weight of 2.5-3kDa, and is purchased from Shanghai-derived leaf Biotechnology GmbH.
Enteric acrylic resin, hydroxypropyl methylcellulose acetate succinate and polyethylene glycol 8000 are uniformly mixed according to the weight ratio of 1:5:1 to be used as a carrier. Wherein the enteric acrylic resin is acrylic resin II, the purchasing manufacturer is Shanghai Yuanye Biotech limited company, the CAS number of the hydroxypropyl methyl cellulose acetate succinate is 71138-97-1, and the purchasing manufacturer is Shenzhen Shangpen Youhui medicine GmbH.
And (2) uniformly mixing the dried nanoparticles and the carrier in a weight ratio of 1:0.3, sieving by a 80-mesh sieve, setting the temperature of a hot-melt extruder to be 110 ℃, the rotating speed to be 60 r/min, crushing the extruded medicine, and sieving by a 60-mesh sieve to obtain the high-stability enteric solid dispersion particles.
Through detection, the average content of EGCG in the final enteric solid dispersion particles is 67.2%, the content of EGCG is higher, and the bioactivity is strong.
Example 2 stability and in vitro Release Performance assay of highly Stable solid Dispersion particles of EGCG
1. An appropriate amount of EGCG raw powder was taken as a control group, the same weight of the solid dispersion particles prepared in example 1 was taken as an experimental group, the experimental group was placed in an open clean container, the container was placed at 60 ℃ for 10 days, samples were taken on the 5 th and 10 th days, and the change in EGCG content was detected by using a high performance liquid chromatograph. The results are shown in Table 1.
TABLE 1 high temperature stability study of enteric particles
Medicine | Day 5 (%) | Day 10 (%) |
EGCG raw powder | 92.4±0.36 | 84.3±0.22 |
Enteric EGCG | 98.9±0.22 | 99.2±0.12 |
The results show that: even under the high-temperature environment condition of 60 ℃, the content of EGCG in the enteric solid dispersion provided by the invention is still as high as 98.9% after being placed for 5 days, the content of EGCG in the enteric solid dispersion provided by the invention is still as high as 99.2% after being placed for 10 days, and particularly, the content of EGCG in the enteric solid dispersion provided by the invention is 17.7% higher than that in the original EGCG powder after being placed for 10 days. The stability of the enteric solid dispersion provided by the invention is very strong.
2. 2g of enteric solid dispersion particles are precisely weighed, 6 parts are weighed, and the particles are respectively placed in a treated dialysis bag and are placed at the bottom of a paddle of a dissolution instrument after being tightened. To simulate the acidic environment of gastric juice and small intestine, 100mL of acidic medium phosphate buffer at pH 2 and pH 6.8 were removed in a 250mL dissolution cup. Keeping the temperature at 37.0 +/-0.5 ℃ and rotating at 50r/min, and sucking 1mL of release medium (simultaneously adding release medium with the same amount and temperature) at 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12, 16 and 24h respectively. The taken-out release medium is filtered by a 0.22 mu m microporous filter membrane, the amount of EGCG is measured by using a high performance liquid chromatograph, and then the cumulative release rate of the EGCG is counted according to the measurement result. The results are shown in FIG. 1.
As can be seen from fig. 1: the release rate of the EGCG is 0% under the gastric juice (pH is 2) environment condition, and the EGCG is gradually released along with the increase of time under the small intestine (pH is 6.8) environment condition, wherein the release rate reaches 100% after about 8 h. The enteric solid dispersion provided by the invention is very stable in gastric acid, basically does not release, can quickly release the nano EGCG in a small intestine environment, and has good slow release performance.
Also, table 1 in conjunction with fig. 1 can also show: the enteric solid dispersion can obviously enhance the stability of EGCG and improve the actual bioavailability of the EGCG in practical application.
Example 3 study of the antibacterial Effect of EGCG
The Minimal Inhibitory Concentration (MIC) of EGCG on clinically separated haemophilus parasuis, riemerella anatipestifer and pasteurella is determined by adopting a broth dilution method, and the MICs of the three bacteria are 512 mu g/mL, 256 mu g/mL and 256 mu g/mL respectively through detection, so that the EGCG shows better inhibition effect on bacterial diseases caused by haemophilus parasuis, riemerella anatipestifer and pasteurella.
Example 4 study of the therapeutic Effect of EGCG highly Stable solid Dispersion particles on Haemophilus parasuis disease
In a certain pig farm in 2016, selecting pigs with poor growth, collecting nasal swabs, determining the pigs with positive haemophilus parasuis infection by bacteria separation identification and PCR detection, dividing 36 pigs into 3 groups, respectively feeding sulfadiazine (30mg/kg, doubled for the first time), EGCG high-stability solid dispersion particles (20mg/kg, calculated according to EGCG) and EGCG raw powder (20mg/kg) for treatment, once a day, continuously using for 3 days, recording the effective rate and death rate of the pigs after three days, and adopting pharyngeal swabs to check the negative conversion rate of haemophilus parasuis. The results are shown in Table 2.
TABLE 2 therapeutic Effect of EGCG on Haemophilus parasuis disease
Medicine | Number of test heads | Effective number of heads | Number of dead heads | Number of vaginal discharge | Negative conversion rate (%) |
Sulfadiazine | 12 | 5 | 3 | 4 | 33.3 |
Enteric EGCG | 12 | 11 | 0 | 10 | 83.3 |
EGCG raw powder | 12 | 6 | 2 | 6 | 50.0 |
The results show that: the EGCG high-stability solid dispersion particle provided by the invention can be well applied to resisting the infection of haemophilus parasuis, and the cure rate of haemophilus parasuis disease reaches 83.3%, is 150% higher than sulfadiazine and is 66.6% higher than the cure rate of EGCG raw powder.
Example 5 study of therapeutic Effect of EGCG highly Stable solid Dispersion particles on Riemerella anatipestifer disease
Selecting ducks died of diseases such as cellulose pericarditis, perihepatitis, air sacculitis and the like in a certain diseased duck farm at the end of 2016, sampling, identifying as riemerella anatipestifer infection through bacterial isolation, selecting 240 diseased ducks divided into 3 groups, feeding enrofloxacin (5mg/kg), EGCG high-stability solid dispersion particles (30mg/kg calculated according to EGCG) and EGCG raw powder (30mg/kg) for treatment respectively, recording the death rate of the diseased ducks after combining for 3 days, randomly selecting 20 ducks, sampling, observing clinical symptoms, and carrying out bacteriological detection. The results are shown in FIG. 3.
TABLE 3 therapeutic Effect of EGCG on Riemerella anatipestifer disease
Medicine | Number of tests | Number of deaths | Number of turning female | Negative conversion rate (%) |
Enrofloxacin | 80 | 35 | 26 | 32.5 |
Enteric EGCG | 80 | 6 | 64 | 80.0 |
EGCG raw powder | 80 | 12 | 28 | 35.0 |
The results show that: the EGCG high-stability solid dispersion particle provided by the invention can be well applied to resisting infection of riemerella anatipestifer, the cure rate of riemerella anatipestifer disease reaches 80.0%, 146% higher than that of enrofloxacin and 129% higher than that of EGCG raw powder.
Example 6 study of the therapeutic Effect of EGCG highly Stable solid Dispersion particles on Crohn's disease
In the end of 2020, the method is researched by a rabbit farm with a certain outbreak of acute respiratory infection, the bacillus basophilus infection is found by sampling and detecting the pulmonary hemorrhage of dead rabbits, 70 cough rabbits are randomly treated by respectively feeding sulfadiazine (30mg/kg, doubled for the first time), EGCG high-stability solid dispersion particles (20mg/kg, calculated according to EGCG) and EGCG raw powder (20mg/kg), and the medicines are mixed and administered for 1 time every day for 3 days. The results are shown in Table 4.
TABLE 4 therapeutic Effect of EGCG on Riemerella anatipestifer disease
Medicine | Number of tests | Number of deaths | Number of turning female | Negative conversion rate (%) |
Enrofloxacin | 20 | 17 | 0 | 0.0 |
Enteric EGCG | 25 | 2 | 20 | 80.0 |
EGCG raw powder | 25 | 10 | 8 | 32.0 |
The results show that: the EGCG high-stability solid dispersion particle provided by the invention can be well applied to infection of the rabbit pasteurella, the cure rate of the rabbit pasteurella diseases also reaches 80.0%, is 150% higher than that of EGCG raw powder, and the cure rate of enrofloxacin is 0%.
While some embodiments of the present invention have been presented herein, it will be appreciated by those skilled in the art that changes may be made to the embodiments herein without departing from the spirit of the invention. The above examples are merely illustrative and should not be taken as limiting the scope of the invention.
Claims (10)
1. Enteric solid dispersion particles based on EGCG nano-particles, characterized in that the dispersion particles are composed of EGCG nano-particles and a carrier, and the average content of EGCG in the dispersion particles is 67.2%.
2. The method of preparing enteric solid dispersion particles of claim 1, comprising the steps of:
(1) preparing nanoparticles: adding a low-molecular-weight chitosan solution into the EGCG solution, fully stirring, adding a sodium tripolyphosphate solution, continuously stirring, centrifuging, collecting precipitate, and vacuum drying;
(2) preparing a carrier: taking a proper amount of enteric acrylic resin, hydroxypropyl methylcellulose acetate succinate and polyethylene glycol 8000, and uniformly mixing to serve as a carrier;
(3) dispersion particles were prepared.
3. The method according to claim 2, wherein the concentration of the low molecular weight chitosan solution in the step (1) is 0.1-0.2%.
4. The method according to claim 3, wherein the concentration of the low molecular weight chitosan solution in the step (1) is 0.15%.
5. The method according to claim 2, wherein the weight ratio of the enteric acrylic resin, hypromellose acetate succinate and polyethylene glycol 8000 in step (2) is 1:5: 1.
6. The preparation method according to claim 2, wherein the weight ratio of the nanoparticles to the carrier in the step (3) is 1:0.1 to 1: 1.
7. The method of claim 6, wherein the weight ratio of the nanoparticles to the carrier in step (3) is 1: 0.3.
8. The use of the enteric solid dispersion particle according to claim 1 or the enteric solid dispersion particle prepared by the preparation method according to any one of claims 2 to 7 for preparing a medicament for preventing and treating bacterial diseases, wherein pathogenic bacteria of the bacterial diseases are haemophilus parasuis, riemerella anatipestifer or pasteurella.
9. The use according to claim 8, wherein the pathogenic bacteria of the bacterial disease are haemophilus parasuis or pasteurella and the enteric solid dispersion is present in an amount of 20 mg/kg.
10. The use according to claim 8, wherein the pathogenic bacteria of the bacterial disease is riemerella anatipestifer and the enteric solid dispersion is present in an amount of 30 mg/kg.
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Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1897975A (en) * | 2003-12-24 | 2007-01-17 | 株式会社三养社 | Nanoparticle compositions of water-soluble drugs for oral administration and preparation methods thereof |
CN1951370A (en) * | 2005-10-22 | 2007-04-25 | 安徽省现代中药研究中心 | Method for preparing solid dispersible minipills of Simvastatin |
WO2012009387A1 (en) * | 2010-07-12 | 2012-01-19 | Salix Pharmaceuticals, Ltd | Formulations of rifaximin and uses thereof |
WO2012139876A1 (en) * | 2011-04-14 | 2012-10-18 | Merz Pharma Gmbh & Co. Kgaa | Enteric formulations of metabotropic glutamate receptor modulators |
CN104719910A (en) * | 2015-04-19 | 2015-06-24 | 福州乾正药业有限公司 | Solid dispersion combination of EGCG (epigallocatechin gallate) with thermal stability and preparation method of solid dispersion combination and application in preparation of solid dispersion combination |
CN106214655A (en) * | 2016-08-29 | 2016-12-14 | 杭州成邦医药科技有限公司 | A kind of solid preparation containing capsaicin and preparation method thereof |
CN108553426A (en) * | 2018-06-01 | 2018-09-21 | 广东药科大学 | A kind of chitosan dripping pill and preparation method thereof |
EP3914591A1 (en) * | 2019-01-25 | 2021-12-01 | BeiGene, Ltd. | Stable solid dispersions of b-raf kinase dimer inhibitor, methods of preparation, and uses therefor |
-
2022
- 2022-01-11 CN CN202210027906.7A patent/CN114366717B/en active Active
Patent Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1897975A (en) * | 2003-12-24 | 2007-01-17 | 株式会社三养社 | Nanoparticle compositions of water-soluble drugs for oral administration and preparation methods thereof |
CN1951370A (en) * | 2005-10-22 | 2007-04-25 | 安徽省现代中药研究中心 | Method for preparing solid dispersible minipills of Simvastatin |
WO2012009387A1 (en) * | 2010-07-12 | 2012-01-19 | Salix Pharmaceuticals, Ltd | Formulations of rifaximin and uses thereof |
WO2012139876A1 (en) * | 2011-04-14 | 2012-10-18 | Merz Pharma Gmbh & Co. Kgaa | Enteric formulations of metabotropic glutamate receptor modulators |
CN104719910A (en) * | 2015-04-19 | 2015-06-24 | 福州乾正药业有限公司 | Solid dispersion combination of EGCG (epigallocatechin gallate) with thermal stability and preparation method of solid dispersion combination and application in preparation of solid dispersion combination |
CN106214655A (en) * | 2016-08-29 | 2016-12-14 | 杭州成邦医药科技有限公司 | A kind of solid preparation containing capsaicin and preparation method thereof |
CN108553426A (en) * | 2018-06-01 | 2018-09-21 | 广东药科大学 | A kind of chitosan dripping pill and preparation method thereof |
EP3914591A1 (en) * | 2019-01-25 | 2021-12-01 | BeiGene, Ltd. | Stable solid dispersions of b-raf kinase dimer inhibitor, methods of preparation, and uses therefor |
Non-Patent Citations (8)
Title |
---|
CAO ET AL.: "Amorphous Solid Dispersion of Epigallocatechin Gallate for Enhanced Physical Stability and Controlled Release", 《PHARMACEUTICALS》 * |
CAO ET AL.: "Amorphous Solid Dispersion of Epigallocatechin Gallate for Enhanced Physical Stability and Controlled Release", 《PHARMACEUTICALS》, vol. 10, no. 88, 31 December 2017 (2017-12-31), pages 1 - 17 * |
LI ET AL.: "Ellagic acid solid dispersion: Characterization and bioactivity in the hydroxyl radical oxidation system", 《FOOD RESEARCH INTERNATIONAL》 * |
LI ET AL.: "Ellagic acid solid dispersion: Characterization and bioactivity in the hydroxyl radical oxidation system", 《FOOD RESEARCH INTERNATIONAL》, vol. 142, 1 February 2021 (2021-02-01), pages 110184 * |
PRUSTY,A. ET AL.: "ROLE OF CHITOSAN AND EUDRAGIT IN POLYMER - BASED EXTENDED RELEASE MATRIX TABLETS - A REVIEW", 《INTERNATIONAL JOURNAL OF PHARMACEUTICAL SCIENCES AND RESEARCH》 * |
PRUSTY,A. ET AL.: "ROLE OF CHITOSAN AND EUDRAGIT IN POLYMER - BASED EXTENDED RELEASE MATRIX TABLETS - A REVIEW", 《INTERNATIONAL JOURNAL OF PHARMACEUTICAL SCIENCES AND RESEARCH》, vol. 8, no. 12, 31 December 2017 (2017-12-31), pages 4973 - 4982, XP055645633 * |
姚洁玉: "鞣花酸固体分散体对带鱼氧化和品质劣变的影响", 《中国优秀硕士学位论文全文数据库工程科技Ⅰ辑》 * |
姚洁玉: "鞣花酸固体分散体对带鱼氧化和品质劣变的影响", 《中国优秀硕士学位论文全文数据库工程科技Ⅰ辑》, no. 02, 15 February 2020 (2020-02-15), pages 024 - 438 * |
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