CN104688692A - Preparation method of novel selenium-rich drug-loading microspheres - Google Patents
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Abstract
The invention discloses a preparation method of novel selenium-rich drug-loading microspheres. The preparation method comprises the following steps: dissolving polylactic acid in methylene chloride, and uniformly dispersing barium selenite in the solution to form an emulsion; injecting the emulsion into a polyvinyl alcohol solution while stirring to form an S/O/W type emulsion; stirring to volatilize dichloromethane, and curing to form spheres; and performing centrifugal washing and drying to obtain the selenium-rich drug-loading microspheres. The selenium-rich drug-loading microspheres disclosed by the invention take barium selenite as a main drug, all components of the drug-loading microspheres are prepared by virtue of reasonable optimization, the drug-loading microspheres are prepared by adopting a coating process of S/O/W and using an emulsion solution volatilization method and are high in drug loading quantity, and the release speed of drugs is controlled by controlling process conditions, thereby reducing the usage amount of barium selenite, prolong the acting time of the drugs, reducing the toxic or side effect of the drugs and improving the curative effect of the drugs.
Description
Technical field
The present invention relates to medicine carrying microballoons technical field, particularly, relate to a kind of preparation method of novel selenium-enriched medicine carrying microballoons.
Background technology
Selenium is as a kind of important trace element, found in 1817 by Sweden chemist Berzelius, in the time later reaching century more than one, people think that all selenium-containing compounds are all noxious substances until nineteen fifty-seven U.S.'s nutritionist Schwarz and Foltz finds that selenium can to prevent after the downright bad and chicken exudative diathesis of Hepar Mus just proposition selenium to be the indispensable trace element of body always.The common concern that since 20 century 70s, the biological function of selenium and the application in animal productiong thereof are subject to people achieves significant results by research extensively and profoundly.Selenium participates in coenzyme A, the synthesis, carbohydrate metabolism, biological oxidation etc. of synthesis on protein of ubiquinone have impact.In body, selenium is general exists with protein bound, such as: the important physiological action of selenium is the ingredient of participation glutathion peroxidase GSH-PX.Recent research finds that selenium is the prothetic group of glutathion peroxidase selenium enzyme family active site, and this fermentoid has removes the effect that peroxide prevents cell injury delaying cell aging.The clinical manifestation of selenium deficiency is mainly degeneration of skeletal muscle, necrosis, liver malnutrition and the heart, hepatic fibrosis etc.Mouse Blood Glutathione Peroxidase (GSH-Px) activity lacking selenium raising obviously reduces lipid peroxide (LPO) content and raises.Therefore Selenium pharaiacology, physiology and biochemistry character cause the interest of people.
In animal selenium-replenishing preparation, conventional selenium source has inorganic selenium to mainly contain selenite, selenate, and organic selenium has paternal yeast, selenomethionine, and the novel selenium-replenishing preparation such as nanometer selenium.Large quantity research shows, relative to selenium products such as selenite, selenomethionine, methylselenocysteines, the better absorbance of nanometer selenium, hypotoxicity, distinctive activity is high, bioavailability is high and the advantage such as the immunity significantly improving animal.Secondly, compared with inorganic selenium, organic selenium has the advantages such as significant high-efficiency low-toxicity, so yeast rich in selenium is also one of the most effective selenium supplement source of current body.At present, the domestic sodium selenite that still uses adds in animal feed as business selenium-replenishing preparation, and American-European countries's many employings selenomethionine is as business selenium-replenishing preparation.Sweden requires must use organic selenium in piglets material; Japan prohibits the use inorganic selenium in regulation feedstuff.Selenomethionine and yeast rich in selenium were once considered to desirable selenium-replenishing preparation; But result of study shows, selenomethionine can replace that methionine is nonspecific to be incorporated in protein, and selenomethionine has the danger building up to toxic level in the tissue.Existing people and poultry are because Excess free enthalpy is containing the relevant report of the food generation selenosis phenomenon of selenomethionine at present.Therefore, determine that some row problems such as the addition manner of organic selenium have to be solved.But the high cost of organic selenium, as yeast selenium is generally several times even tens times of selenite, therefore will consider the economic problems such as cost.The inorganic selenium source generally recommended at present is barium selenite, it is main because it has longer demurrage in animal body, sodium selenite is 119 days, barium selenite can reach more than 140 days, and toxicity is lower relative to sodium selenite, but barium selenite is water insoluble, must make oleaginous suspension, suspendible barium selenite preparation as newborn in Muscovite oil, the barium selenite Emulsion of Jie Bolin and Britain can reach the high blood selenium level of long period in an experiment.Along with the development of preparation new technology and slow release delay the application of control techniques, reduce inorganic selenium toxicity by the release mode that microsphere is special, thus reduce dosage and alleviate body burden.
Polylactic acid (polylactic acid or polylactide, PLA) be with fast-growing resource Semen Maydis for primary raw material, obtain lactic acid through fermentation, then be that primary raw material is polymerized the polymer obtained with lactic acid.Polylactic acid has good thermoplasticity and thermosetting, there is biocompatibility and biodegradable simultaneously, in human body, final metabolism is water and carbon dioxide, is the biodegradation material that FDA (Food and Drug Adminstration) (FDA) approved can be used for human body.Therefore adopting with polylactide and its copolymer be the biodegradable polymer of representative is framework material, and parcel polypeptide, pharmaceutical grade protein make sustained release microsphere agents, become the focus of preparation research.And large quantity research has done in the preparation method, mode of appearance, releasing mechanism etc. of polylactic acid microsphere in the current developed country such as American-European-Japanese.Domesticly also there is a collection of polylactic acid microsphere medically applied, as Polylactic Acid Microspheres Loading Ivermectin, rifampicin polylactic acid microsphere and penetrating judgment polylactic acid microsphere etc.
But sustained-release micro-spheres is also few in the application of field of veterinary, and in selenium-replenishing preparation, have no the correlational study report of rich selenium sustained-release micro-spheres.Tradition selenium preparation mostly is oil emulsion type, during by muscle injection mode administration, because the rate of release that effectively can not control medicine causes animal body local drug concentration too high, and may produce inflammatory reaction, diseases induced generation.
Summary of the invention
The object of the invention is to for the deficiencies in the prior art, a kind of preparation method of novel selenium-enriched medicine carrying microballoons is provided.Described rich selenium medicine carrying microballoons take barium selenite as principal agent, adopt Biodegradable material polylactic acid as clad material, emulsified solution volatility process is utilized to be prepared into medicine carrying microballoons, its drug loading is high, and control the rate of release of medicine by Controlling Technology condition, thus reduce barium selenite use amount, the action time of prolong drug, reduce the toxic and side effects of medicine, improve the curative effect of medicine.
Object of the present invention is achieved by the following technical programs.
A preparation method for novel selenium-enriched medicine carrying microballoons, comprises the steps:
S1. by 1 ~ 8 part of barium selenite powder micronization, add in 10 ~ 25 parts of dichloromethane, ultrasonic disperse, ultrasonic power is 100 ~ 200W, and jitter time is 30min;
S2. be dissolved in 100 ~ 300 parts of dichloromethane by 4 ~ 12 parts of polylactic acid, mix homogeneously forms solution;
S3. be dispersed in solution described in S2 by the mixture that S1 obtains, mix homogeneously forms emulsion;
S4. be dissolved in 1000 ~ 5000 parts of water by 1 ~ 100 part of polyvinyl alcohol, then add 20 ~ 100 parts of NaCl, heating mix homogeneously forms poly-vinyl alcohol solution;
S5. join in poly-vinyl alcohol solution described in S4 by the emulsion that S3 is formed again, mix homogeneously forms S/O/W type emulsion;
S6. the emulsion that stirring S5 obtains makes dichloromethane volatilize, solidification balling-up, then through centrifugal, washing, drying, obtains described rich selenium medicine carrying microballoons;
Wherein, barium selenite is principal agent; Described polylactic acid molecule amount is 100000;
The number of described barium selenite, dichloromethane, polylactic acid PLA, PVAC polyvinylalcohol, NaCl and water is parts by weight.
Because barium selenite is water-soluble hardly, prior art is oil emulsion injection mainly, and dosage is comparatively large, and barium selenite has certain toxicity, can cause a series of harmful effect to body, is unfavorable for applying in selenium-replenishing preparation.The present invention is by the ultrasonic disperse pretreatment of barium selenite, good solution barium selenite disperses difficult problem in a solvent, the dissolubility of barium selenite determines decentralized approach, prove to use aqueous solvent to dissolve dispersion effect by lot of experiments not good, selecting dichloromethane as both shared solvents to reach dispersion effect synchronous with PLA, adopting ultrasonic disperse mode to avoid dichloromethane in dispersive process to volatilize the injury caused; In poly-vinyl alcohol solution, add a certain amount of NaCl, change the osmotic pressure of dispersion and be conducive to microsphere and formed rapidly and surface hole defect is less; And reasonably optimizing prepares each constituent content of medicine carrying microballoons, adopt the bag of S/O/W by technique, S/O/W difficult point is institute's encrusting substance matter dispersion in a solvent and material grains, need the dispersed rear easy formation microsphere of micronization, emulsified solution volatility process is utilized to be prepared into rich selenium medicine carrying microballoons, its drug loading is high, and the rate of release of medicine is controlled by Controlling Technology condition, thus reduce barium selenite use amount, the action time of prolong drug, reduce the toxic and side effects of medicine, improve the curative effect of medicine.
Preferably, the mean diameter of the rich selenium medicine carrying microballoons prepared is 3.52 ~ 20.34 μm.
Preferably, the drug loading of the rich selenium medicine carrying microballoons prepared is 17.5 ~ 25.3%.
Mixing described in S2, S3, S4, S5 can adopt ultrasound wave to disperse or mechanical agitation dispersion.
When adopting ultrasound wave dispersion, preferably, mixing described in S3 adopts ultrasound wave dispersion, and ultrasonic power is 100W, and jitter time is 1 ~ 3h.Preferably, mixing described in S2, S5 adopts ultrasound wave dispersion, and ultrasonic power is 100W, and jitter time is 1 ~ 3h.
When adopting mechanical agitation dispersion, preferably, mixing described in S3 adopts mechanical agitation, and rotating speed is 5000 ~ 15000 rmin
-1, mixing time is 30s ~ 1min.Preferably, mixing described in S2 adopts mechanical agitation, and rotating speed is 300 ~ 500 rmin
-1, mixing time is 20 ~ 40min.Preferably, mixing described in S5 adopts mechanical agitation, and rotating speed is 300 ~ 500 rmin
-1, mixing time is 6 ~ 20h.
Preferably, wash described in S6 cleaning mixture used be deionized water or/and hydrochloric acid, wash 3 ~ 5 times altogether.
Preferably, described in S6, washing is for use deionized water wash 2 ~ 3 times respectively, with 5% salt acid elution 1 ~ 2 time.
Preferably, drying described in S6 is that normal-temperature vacuum is dry, is kept in Dark Place by the medicine carrying microballoons prepared after drying in 4 DEG C.
Compared with prior art, the present invention has following beneficial effect:
(1) rich selenium medicine carrying microballoons of the present invention take barium selenite as principal agent, by the ultrasonic disperse pretreatment of barium selenite, ultrasonic disperse uses ultrasonic probe usually, this method adopts closed ultrasonic, added by institute's ultrasonic disperse material and carry out ultrasonic in hermetic container, when this method effectively can avoid ultrasonic disperse, material and solvent volatilize the unnecessary injury caused; In poly-vinyl alcohol solution, add a certain amount of NaCl, promoting that microsphere is formed by improving aqueous phase osmotic pressure, reducing because dichloromethane volatilizees the microsphere surface hole caused, being conducive to microsphere and reaching better slow release effect; And each constituent content of medicine carrying microballoons is prepared by reasonably optimizing, adopt the bag of S/O/W by technique, emulsified solution volatility process is utilized to be prepared into medicine carrying microballoons, its drug loading is high, and control the rate of release of medicine by Controlling Technology condition, thus reduce barium selenite use amount, the action time of prolong drug, reduce the toxic and side effects of medicine, improve the curative effect of medicine.
(2) preparation method technological process of the present invention is simple, and the mean diameter of the rich selenium medicine carrying microballoons prepared is 3.52 ~ 20.34 μm, and drug loading is 17.5 ~ 25.3%, and drug loading is large and reproducible.
(3) the present invention adopt principal agent be inorganic selenium barium selenite, with low cost, toxicity is lower, and in vivo the holdup time long, be therefore prepared into medicine carrying microballoons and be generalized to field of veterinary, have good social benefit and economic interests prospect.
(4) lapping that the present invention adopts is industrial injection grade polylactic acid PLA, and cost of material is cheap, and preparation does not need special expensive equipment, and technological process is simple, and medicine carrying microballoons has good biocompatibility.
Accompanying drawing explanation
Fig. 1 is that embodiment 1 barium selenite medicine carrying microballoons SEM schemes.
Fig. 2 is that embodiment 2 barium selenite medicine carrying microballoons SEM schemes.
Fig. 3 is the external release profiles of embodiment 2 barium selenite medicine carrying microballoons.
Fig. 4 is that embodiment 3 barium selenite medicine carrying microballoons SEM schemes.
Fig. 5 is the external release profiles of embodiment 3 barium selenite medicine carrying microballoons.
Fig. 6 is that comparative example 1 barium selenite medicine carrying microballoons SEM schemes.
Fig. 7 is that comparative example 2 barium selenite medicine carrying microballoons SEM schemes.
Fig. 8 is that comparative example 3 barium selenite medicine carrying microballoons SEM schemes.
Fig. 9 is that comparative example 4 barium selenite medicine carrying microballoons SEM schemes.
Figure 10 is the external release profiles of comparative example 4 barium selenite medicine carrying microballoons.
Detailed description of the invention
The present invention is elaborated further below in conjunction with Figure of description and specific embodiment.But embodiment does not limit in any form the present invention.Unless stated otherwise, the present invention adopts reagent, method and apparatus are the art conventional reagent, method and apparatus.
embodiment 1
A preparation method for novel selenium-enriched medicine carrying microballoons, comprises the steps:
S1. by 1g barium selenite powder micronization, add in 2 ~ 6mL dichloromethane, ultrasonic disperse, ultrasonic power is 100W, and jitter time is 30min;
S2. be dissolved in 20 ~ 50mL dichloromethane by 1.2g polylactic acid PLA, ultrasound wave disperses, and ultrasonic power is 100W, and jitter time is 3h, forms solution;
S3. be dispersed in solution described in S2 by the mixture that S1 obtains, mechanical agitation, rotating speed is 15000 rmin
-1, stir 30s, form emulsion;
S4. be dissolved in 100 ~ 300mL water by 0.6g polyvinyl alcohol, then add 1.5 ~ 5gNaCl, heating mix homogeneously forms poly-vinyl alcohol solution;
S5. join in poly-vinyl alcohol solution described in S4 by the emulsion that S3 is formed again, mechanical agitation, rotating speed is 15000 rmin
-1, stir 6h, form S/O/W type emulsion;
S6. stirring the emulsion that obtains of S5 makes dichloromethane volatilize, solidification balling-up, more centrifugal through 8000rpm, deionized water wash 3 times, uses 5% salt acid elution 2 times again, and normal-temperature vacuum drying, obtains described rich selenium medicine carrying microballoons, keep in Dark Place in 4 DEG C;
Wherein, barium selenite is principal agent; Described polylactic acid molecule amount is 100000.
The particle diameter of the rich selenium medicine carrying microballoons prepared is 5.23 ~ 20.04 μm, and drug loading is 20 ~ 25%, and the SEM of medicine carrying microballoons as shown in Figure 1.
embodiment 2
A preparation method for novel selenium-enriched medicine carrying microballoons, comprises the steps:
S1. by 0.5g barium selenite powder micronization, add in 1 ~ 3mL dichloromethane, ultrasonic disperse, ultrasonic power is 200W, and jitter time is 30min;
S2. be dissolved in 12 ~ 40ml dichloromethane by 1g polylactic acid PLA, mechanical agitation, rotating speed is 500 rmin
-1, mixing time is 20min, forms solution;
S3. be dispersed in solution described in S2 by the mixture that S1 obtains, mechanical agitation, rotating speed is 15000 rmin
-1, stir 30s, form emulsion;
S4. be dissolved in 100 ~ 300 water by 0.8 polyvinyl alcohol, then add 1.5 ~ 5gNaCl, heating mix homogeneously forms poly-vinyl alcohol solution;
S5. join in poly-vinyl alcohol solution described in S4 by the emulsion that S3 is formed again, ultrasound wave disperses, and ultrasonic power is 100W, dispersion 3h, forms S/O/W type emulsion;
S6. stirring the emulsion that obtains of S5 makes dichloromethane volatilize, solidification balling-up, more centrifugal through 8000rpm, deionized water wash 1 time, uses 5% salt acid elution 2 times again, and normal-temperature vacuum drying, obtains described rich selenium medicine carrying microballoons, keep in Dark Place in 4 DEG C;
Wherein, barium selenite is principal agent; Described polylactic acid molecule amount is 100000.
The particle diameter of the rich selenium medicine carrying microballoons prepared is 6.48 ~ 18.45 μm, and drug loading is 21 ~ 25%, and the SEM of medicine carrying microballoons as shown in Figure 2.
Upper described rich selenium medicine carrying microballoons is carried out conventional vitro drug release test experiments, the drug release rate that the present embodiment barium selenite medicine carrying microballoons discharges in liquid (0.1MHC) in acidity is comparatively mild, and after 24h, release rate is 5%, and after 69d, release rate is 10%.Drug release rate in neutral buffer (pH value is the phosphate buffered solution of 7.4) is obviously slow, and after 24h, release rate is 3%, and after 69d, release rate is 5.9%.Result as shown in Figure 3.
embodiment 3
A preparation method for novel selenium-enriched medicine carrying microballoons, comprises the steps:
S1. by 0.8g barium selenite powder micronization, add in 1.5 ~ 5mL dichloromethane, ultrasonic disperse, ultrasonic power is 150W, and jitter time is 30min;
S2. be dissolved in 12 ~ 40ml dichloromethane by 1.5g polylactic acid PLA, mechanical agitation, rotating speed is 350 rmin
-1, mixing time is 30min, forms solution;
S3. be dispersed in solution described in S2 by the mixture that S1 obtains, mechanical agitation, rotating speed is 10000 rmin
-1, stir 50s, form emulsion;
S4. be dissolved in 100 ~ 300mL water by 0.8g polyvinyl alcohol, then add 2 ~ 6gNaCl, heating mix homogeneously forms poly-vinyl alcohol solution;
S5. join in poly-vinyl alcohol solution described in S4 by the emulsion that S3 is formed again, ultrasound wave disperses, and ultrasonic power is 100W, dispersion 2.5h, forms S/O/W type emulsion;
S6. stirring the emulsion that obtains of S5 makes dichloromethane volatilize, solidification balling-up, more centrifugal through 8000rpm, and through 5% salt acid elution 4 times, normal-temperature vacuum drying, obtains described rich selenium medicine carrying microballoons, keep in Dark Place in 4 DEG C;
Wherein, barium selenite is principal agent; Described polylactic acid molecule amount is 100000.
The particle diameter of the rich selenium medicine carrying microballoons prepared is 4.63 ~ 20.18 μm, and drug loading is 20.47 ~ 24.26%, and the SEM of medicine carrying microballoons as shown in Figure 4.
Above-mentioned medicine carrying microballoons is carried out conventional vitro drug release test experiments, the drug release rate that the present embodiment barium selenite medicine carrying microballoons discharges in liquid (0.1MHC) in acidity is comparatively mild, and after 24h, release rate is 7.4%, and after 300h, release rate is 15.9%.Drug release rate in neutral buffer (pH value is the phosphate buffered solution of 7.4) is obviously slow, and after 24h, release rate is 3.7%, and after 300h, release rate is 6.3%.Result as shown in Figure 5.
comparative example 1
The preparation method that this comparative example and embodiment 3 prepare rich selenium medicine carrying microballoons is substantially identical, difference is that the processing method of this comparative example to described S1 step is: process 1.-0.8g barium selenite powder micronization is used for subsequent step, without the supersound process of barium selenite; Process 2.-by 0.8g barium selenite powder micronization, add in 0.5 ~ 1mL dichloromethane, ultrasonic disperse, ultrasonic power is 70W, and jitter time is 40min.
The particle diameter processing the rich selenium medicine carrying microballoons 1. prepared is 3.04 ~ 36.89 μm, and drug loading is 9.17% ~ 13.43%; The particle diameter processing the rich selenium medicine carrying microballoons 2. prepared is 4.08 ~ 30.47 μm, and drug loading is 11.46% ~ 15.95%.Process 1. with process 2. to barium selenite without pretreatment or deal with improperly, affect the deployment conditions of barium selenite granule in first Ruzhong, and then the reaction of the prepared oil phase of impact and barium selenite, cause bag uneven by microspherulite diameter, drug loading reduces, drug loss rate improves, and the SEM of medicine carrying microballoons as shown in Figure 6.
comparative example 2
The preparation method that this comparative example and embodiment 3 prepare rich selenium medicine carrying microballoons is substantially identical, and difference is that the processing method of this comparative example to described S4 step is: process 1.-poly-vinyl alcohol solution not adding NaCl is used for subsequent step; Process 2.-0.3g polyvinyl alcohol is dissolved in 100 ~ 300mL water, then add 0.5gNaCl, heating mix homogeneously forms poly-vinyl alcohol solution.
The particle diameter processing the rich selenium medicine carrying microballoons 1. prepared is 5.89 ~ 18.46 μm, and drug loading is 10.89 ~ 13.12%; The particle diameter processing the rich selenium medicine carrying microballoons 2. prepared is 4.56 ~ 20.03 μm, drug loading is 12.72 ~ 16.47%, process 1. with process 2. to not salt adding or add concentration not at proper range in aqueous phase, the osmotic pressure of aqueous phase and oil phase can be affected, the change of system osmotic pressure causes the water in aqueous phase to flow into oil phase, the hole stayed at microsphere formation stages microsphere surface is exactly water is entered oil phase proof by aqueous phase, microsphere surface hole more many being more unfavorable for plays slow release effect, and the SEM of medicine carrying microballoons as shown in Figure 7.
comparative example 3
The preparation method that this comparative example and embodiment 3 prepare rich selenium medicine carrying microballoons is substantially identical, and difference is that the processing method of this comparative example to described S2 step is: the molecular weight of process 1.-described polylactic acid PLA is 50000; The molecular weight of process 2.-described polylactic acid PLA is 150000.
The particle diameter processing the rich selenium medicine carrying microballoons 1. prepared is 2.13 ~ 13.79 μm, and drug loading is 8.78 ~ 10.16%; The particle diameter processing the rich selenium medicine carrying microballoons 2. prepared is 7.46 ~ 40.15 μm, and drug loading is 4.17% ~ 9.72%.When 2. 1. process use low-molecular-weight and high molecular PLA to prepare microsphere with process respectively, the less viscosity of mixed liquid of molecular weight of PLA diminishes, and forms microspherulite diameter less, cause drug loading to reduce when high dispersive power; The molecular weight of PLA is larger or concentration is higher all can cause, and mixed liquor medium viscosity is excessive, when dispersion force is inadequate, is difficult to balling-up, causes lower drug loading and envelop rate, and the SEM of medicine carrying microballoons as shown in Figure 8.
comparative example 4
A preparation method for novel selenium-enriched medicine carrying microballoons, comprises the steps:
S1. by 0.8g barium selenite powder micronization, add in 3 ~ 5ml dichloromethane, ultrasonic disperse, ultrasonic power is 150W, and jitter time is 30min;
S2. be dissolved in 10ml dichloromethane by 2.5g polylactic acid PLA, mechanical agitation, rotating speed is 350 rmin
-1, mixing time is 30min, forms solution;
S3. be dispersed in solution described in S2 by the mixture that S1 obtains, mechanical agitation, rotating speed is 10000 rmin
-1, stir 50s, form emulsion;
S4. be dissolved in 100 ~ 200 water by 1.5 polyvinyl alcohol, then add 1 ~ 4gNaCl, heating mix homogeneously forms poly-vinyl alcohol solution;
S5. join in poly-vinyl alcohol solution described in S4 by the emulsion that S3 is formed again, ultrasound wave disperses, and ultrasonic power is 100W, dispersion 2.5h, forms S/O/W type emulsion;
S6. the emulsion that stirring S5 obtains makes dichloromethane volatilize, solidification balling-up, more centrifugal through 8000rpm, and through 1 deionized water wash and 1 5% salt acid elution, normal-temperature vacuum is dry, obtains described rich selenium medicine carrying microballoons, keeps in Dark Place in 4 DEG C;
Wherein, barium selenite is principal agent; Described polylactic acid molecule amount is 100000.
The particle diameter of the rich selenium medicine carrying microballoons prepared is 5.04 ~ 41.17 μm, and drug loading is 7.15 ~ 10.46, and the SEM of medicine carrying microballoons as shown in Figure 9.
Above-mentioned medicine carrying microballoons is carried out conventional vitro drug release test experiments, the drug release rate that this comparative example barium selenite medicine carrying microballoons discharges in liquid (0.1MHCL) in acidity is comparatively mild, and after 24h, release rate is 18.35%, and after 300h, release rate is 28.15%.Drug release rate in neutral buffer (pH value is the phosphate buffered solution of 7.4) is obviously slow, and after 24h, release rate is 13.27%, and after 300h, release rate is 17.98%, and result as shown in Figure 10.
Claims (8)
1. a preparation method for novel selenium-enriched medicine carrying microballoons, is characterized in that, comprises the steps:
S1. by 1 ~ 8 part of barium selenite powder micronization, add in 10 ~ 25 parts of dichloromethane, ultrasonic disperse, ultrasonic power is 100 ~ 200W, and jitter time is 30min;
S2. be dissolved in 100 ~ 300 parts of dichloromethane by 4 ~ 12 parts of polylactic acid, mix homogeneously forms solution;
S3. be dispersed in solution described in S2 by the mixture that S1 obtains, mix homogeneously forms emulsion;
S4. be dissolved in 1000 ~ 5000 parts of water by 1 ~ 100 part of polyvinyl alcohol, then add 20 ~ 100 parts of NaCl, heating mix homogeneously forms poly-vinyl alcohol solution;
S5. join in poly-vinyl alcohol solution described in S4 by the emulsion that S3 is formed again, mix homogeneously forms S/O/W type emulsion;
S6. the emulsion that stirring S5 obtains makes dichloromethane volatilize, solidification balling-up, then through centrifugal, washing, drying, obtains described rich selenium medicine carrying microballoons;
Wherein, barium selenite is principal agent; Described polylactic acid molecule amount is 100000;
The number of described barium selenite, dichloromethane, polylactic acid, polyvinyl alcohol, NaCl and water is parts by weight.
2. preparation method according to claim 1, is characterized in that, the mean diameter of the rich selenium medicine carrying microballoons prepared is 3.52 ~ 20.34 μm.
3. preparation method according to claim 2, is characterized in that, the drug loading of the rich selenium medicine carrying microballoons prepared is 17.5 ~ 25.3%.
4. preparation method according to claim 1, is characterized in that, mixing described in S3 adopts ultrasound wave dispersion, and ultrasonic power is 100W, and jitter time is 1 ~ 3h.
5. preparation method according to claim 1, is characterized in that, mixing described in S3 adopts mechanical agitation, and rotating speed is 5000 ~ 15000 rmin
-1, mixing time is 30s ~ 1min.
6. preparation method according to claim 1, is characterized in that, wash described in S6 cleaning mixture used be deionized water or/and hydrochloric acid, wash 3 ~ 5 times altogether.
7. preparation method according to claim 6, is characterized in that, described in S6, washing is for use deionized water wash 2 ~ 3 times respectively, with 5% salt acid elution 1 ~ 2 time.
8. preparation method according to claim 1, is characterized in that, drying described in S6 is that normal-temperature vacuum is dry, is kept in Dark Place by the medicine carrying microballoons prepared after drying in 4 DEG C.
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| CN112755004A (en) * | 2020-12-04 | 2021-05-07 | 广东省医疗器械研究所 | Drug-loaded composite microsphere and preparation method and application thereof |
| CN113636890A (en) * | 2021-09-18 | 2021-11-12 | 成都正光投资集团有限公司 | Selenium-rich slow-release cadmium inhibitor and preparation method thereof |
| CN116262157A (en) * | 2022-12-29 | 2023-06-16 | 高颜苑科技(深圳)有限责任公司 | Preparation method of polypeptide slow-release microneedle based on hair growth |
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| CN112755004A (en) * | 2020-12-04 | 2021-05-07 | 广东省医疗器械研究所 | Drug-loaded composite microsphere and preparation method and application thereof |
| CN113636890A (en) * | 2021-09-18 | 2021-11-12 | 成都正光投资集团有限公司 | Selenium-rich slow-release cadmium inhibitor and preparation method thereof |
| CN113636890B (en) * | 2021-09-18 | 2022-04-15 | 成都正光投资集团有限公司 | Selenium-rich slow-release cadmium inhibitor and preparation method thereof |
| CN116262157A (en) * | 2022-12-29 | 2023-06-16 | 高颜苑科技(深圳)有限责任公司 | Preparation method of polypeptide slow-release microneedle based on hair growth |
| CN116262157B (en) * | 2022-12-29 | 2024-05-10 | 高颜苑科技(深圳)有限责任公司 | Preparation method of polypeptide slow-release microneedle based on hair growth |
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| CN104688692B (en) | 2017-06-20 |
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