CN104688692B - A kind of preparation method of novel selenium-enriched drug bearing microsphere - Google Patents
A kind of preparation method of novel selenium-enriched drug bearing microsphere Download PDFInfo
- Publication number
- CN104688692B CN104688692B CN201510099844.0A CN201510099844A CN104688692B CN 104688692 B CN104688692 B CN 104688692B CN 201510099844 A CN201510099844 A CN 201510099844A CN 104688692 B CN104688692 B CN 104688692B
- Authority
- CN
- China
- Prior art keywords
- selenium
- drug bearing
- bearing microsphere
- preparation
- dichloromethane
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Landscapes
- Manufacturing Of Micro-Capsules (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses a kind of preparation method of novel selenium-enriched drug bearing microsphere.Be dissolved in PLA in dichloromethane by the present invention, barium selenite is dispersed in above-mentioned solution again, form emulsion, this emulsion is injected into poly-vinyl alcohol solution under stirring, formed S/O/W type emulsions, then it is agitated dichloromethane is volatilized, solidify balling-up, dried by centrifuge washing, obtain selenium-rich drug bearing microsphere.Selenium-rich drug bearing microsphere of the present invention is with barium selenite as main ingredient, the each component content of drug bearing microsphere is prepared by reasonably optimizing, using the coating technique of S/O/W, drug bearing microsphere is prepared into using emulsified solution volatility process, its drugloading rate is high, and can be by controlling the rate of release of process regulation medicine, so as to reduce barium selenite usage amount, extend the action time of medicine, reduce the toxic and side effect of medicine, improve the curative effect of medicine.
Description
Technical field
The present invention relates to drug bearing microsphere technical field, in particular it relates to a kind of preparation method of novel selenium-enriched drug bearing microsphere.
Background technology
Selenium was found, later up to one in 1817 as a kind of important trace element by Sweden chemist Berzelius
People think that all selenium-containing compounds are all noxious materials until nineteen fifty-seven U.S. nutritionist always in the time in individual many centuries
Schwarz and Foltz have found that selenium can just propose that selenium is indispensable body after pre- protection against rodents hepatonecrosis and chicken exudative diathesis
Trace element.The biological function of selenium and its application in animal productiong are subject to the generally pass of people since 20 century 70s
Note achieves significant results by research extensively and profoundly.Selenium participates in synthesis, sugared generation of the synthesis of coacetylase, ubiquinone to protein
Thank, biological oxidation etc. all has an impact.Internal selenium is typically combined presence with protein, for example：The important physiological action of selenium is to participate in paddy
The part of the sweet peptide peroxidase GSH- PX of Guang.Recently research finds that selenium is glutathione peroxidase selenium enzyme family
The prothetic group of active site, the fermentoid prevents the effect of cellular damage delaying cell aging with peroxide is removed.Selenium deficiency
Clinical manifestation be mainly that degeneration of skeletal muscle, necrosis, liver be malnutritive and the heart, hepatic fibrosis etc..The mouse blood that selenium deficiency is raised
Glutathione Peroxidase (GSH- Px) activity substantially reduces MDA (LPO) content and raises.Therefore the medicine of selenium
Of science, physiology and biochemistry property causes the interest of people.
In animal selenium-replenishing preparation, conventional selenium source has the inorganic selenium mainly to have selenite, selenate, and Organic Selenium has
Paternal yeast, selenomethionine, and the new selenium-replenishing preparation such as nanometer selenium.Numerous studies show, relative to selenite, seleno
The selenium product such as methionine, methylselenocysteine, the more preferable absorptivity of nanometer selenium, hypotoxicity, distinctive activity is high, biological profit
With rate it is high and significantly improve animal immunity the advantages of.Secondly, compared with inorganic selenium, Organic Selenium has significant high-efficiency low-toxicity
The advantages of, so Se-enriched yeast is also one of maximally effective selenium-supply source of current body.At present, the country is still made using sodium selenite
For business selenium-replenishing preparation is added in animal feed, using selenomethionine as business selenium-replenishing preparation more than American-European countries.Sweden
It is required that Organic Selenium must be used in sucking pig material；Inorganic selenium is prohibitted the use of in Japanese regulation feed.Selenomethionine and selenium-rich ferment
Mother was once considered as preferable selenium-replenishing preparation；But result of study shows, selenomethionine can replace methionine non-specific
Incorporate protein, selenomethionine has the danger for building up to toxic level in the tissue.At present someone and livestock and poultry due to
There is the relevant report of selenosis phenomenon in food of the Excess free enthalpy containing selenomethionine.Accordingly, it is determined that the addition manner of Organic Selenium
Have to be solved Deng some row problems.But the high cost of Organic Selenium, such as yeast selenium are usually several times even tens of selenite
Times, therefore to consider the economic problems such as cost.The inorganic selenium source for commonly recommending at present is barium selenite, is primarily due to it dynamic
There is demurrage more long in object, sodium selenite is 119 days, and barium selenite can reach more than 140 days, and toxicity is with respect to selenous acid
Sodium is relatively low, but barium selenite is water insoluble, must make oleaginous suspension, such as the oil breast suspension barium selenite preparation of Russia, outstanding
The barium selenite emulsion of ripple woods and Britain is attained by the blood selenium level high of long period in an experiment.With preparation new technology
Development and the application of the slow control technology of sustained release, reduce inorganic selenium toxicity, so as to reduce administration by the special release mode of microballoon
Amount mitigates body burden.
PLA (polylactic acid or polylactide, PLA) is with fast-growing resource corn as main former
Material, fermented prepared lactic acid, then be the polymer that main polymerizable raw material is obtained with lactic acid.PLA have good thermoplasticity and
Thermosetting, while having biocompatibility and biodegradable, finally water and carbon dioxide is metabolized as in human body, is the U.S.
Food and Drug Admistraton (FDA) approved can be used for the biodegradation material of human body.Therefore use with polylactide and its copolymer
For the biodegradable polymer for representing is framework material, parcel polypeptide, pharmaceutical grade protein are made sustained release microsphere agents, as system
The focus of agent research.And preparation method, mode of appearance, releasing mechanism etc. of the developed country such as American-European-Japanese in polylactic acid microsphere at present
Aspect has done numerous studies.Also there is a collection of polylactic acid microsphere medically applied in the country, such as Polylactic Acid Microspheres Loading Ivermectin,
Rifampin polylactic acid microsphere and penetrating judgment polylactic acid microsphere etc..
However, sustained-release micro-spheres are simultaneously few in the application of field of veterinary, and selenium-rich sustained-release micro-spheres are had no in selenium-replenishing preparation
Correlative study report.Traditional selenium preparation is generally oil emu type, when being administered by muscle injection mode, due to can not effectively control
The rate of release of medicine causes animal body local drug concentration too high, and there may be inflammatory reaction, triggers disease to produce.
The content of the invention
The purpose of the present invention is to solve the shortcomings of the prior art, there is provided a kind of preparation side of novel selenium-enriched drug bearing microsphere
Method.The selenium-rich drug bearing microsphere is with barium selenite as main ingredient, using Biodegradable material PLA as covering material, profit
Drug bearing microsphere is prepared into emulsified solution volatility process, its drugloading rate is high, and can be by controlling the release of process regulation medicine
Speed, so as to reduce barium selenite usage amount, extends the action time of medicine, reduces the toxic and side effect of medicine, improves medicine
Curative effect.
The purpose of the present invention is achieved by the following technical programs.
A kind of preparation method of novel selenium-enriched drug bearing microsphere, comprises the following steps：
S1. 1 ~ 8 part of barium selenite powder is micronized, in 10 ~ 25 parts of dichloromethane of addition, ultrasonic disperse, ultrasonic wave work(
Rate is 100 ~ 200W, and jitter time is 30min；
S2. 4 ~ 12 parts of PLAs are dissolved in 100 ~ 300 parts of dichloromethane, it is well mixed to form solution；
S3. the mixture that S1 is obtained is dispersed in solution described in S2, it is well mixed to form emulsion；
S4. 1 ~ 100 part of polyvinyl alcohol is dissolved in 1000 ~ 5000 parts of water, adds 20 ~ 100 parts of NaCl, heating mixing
It is formed uniformly poly-vinyl alcohol solution；
S5. the emulsion that S3 is formed is added in poly-vinyl alcohol solution described in S4 again, it is well mixed to form S/O/W types breast
Liquid；
S6. the emulsion that stirring S5 is obtained makes dichloromethane volatilize, and solidifies balling-up, then through being centrifuged, washing, dry, obtain institute
State selenium-rich drug bearing microsphere；
Wherein, barium selenite is main ingredient；The polylactic acid molecule amount is 100000；
The number of the barium selenite, dichloromethane, polylactic acid PLA, PVAC polyvinylalcohol, NaCl and water is weight portion
Number.
Because barium selenite is practically insoluble in water, prior art is mainly oil emulsion injection, and dosage is larger, and selenous acid
Barium has certain toxicity, and a series of harmful effects can be caused to body, is unfavorable for being applied in selenium-replenishing preparation.The present invention is by Asia
The ultrasonic disperse pretreatment of barium selenate, solves the problems, such as that barium selenite disperses hardly possible, the dissolving of barium selenite in a solvent well
Property determine decentralized approach, by lot of experiments prove using aqueous solvent dissolve dispersion effect it is not good, it is same with PLA in order to reach
Step dispersion effect, as both shared solvents, the dichloro in dispersion process is avoided using ultrasonic disperse mode from dichloromethane
The injury that methane volatilization is caused；A certain amount of NaCl is added in poly-vinyl alcohol solution, the osmotic pressure for changing dispersion is favourable
Quickly formed in microballoon and surface hole defect is less；And reasonably optimizing prepares each component content of drug bearing microsphere, using S/O/W's
Coating technique, S/O/W difficult points are be coated with material decentralization and material grainses in a solvent, need to be micronized it is dispersed after
Microballoon is easily formed, selenium-rich drug bearing microsphere is prepared into using emulsified solution volatility process, its drugloading rate is high, and can be by controlling technique
Condition controls the rate of release of medicine, so as to reduce barium selenite usage amount, extends the action time of medicine, reduces the poison of medicine
Side effect, improves the curative effect of medicine.
Preferably, the average grain diameter of the selenium-rich drug bearing microsphere for preparing is 3.52 ~ 20.34 μm.
Preferably, the drugloading rate of the selenium-rich drug bearing microsphere for preparing is 17.5 ~ 25.3%.
Mixing described in S2, S3, S4, S5 can be using ultrasonic wave dispersion or mechanical agitation dispersion.
When being disperseed using ultrasonic wave, it is preferable that mix described in S3 using ultrasonic wave dispersion, ultrasonic power is 100W, point
The time of dissipating is 1 ~ 3h.Preferably, mixing described in S2, S5 using ultrasonic wave dispersion, ultrasonic power is 100W, jitter time is 1 ~
3h。
When being disperseed using mechanical agitation, it is preferable that mixing described in S3 uses mechanical agitation, rotating speed is 5000 ~ 15000 r
min-1, mixing time is 30s ~ 1min.Preferably, mixing described in S2 uses mechanical agitation, and rotating speed is 300 ~ 500 rmin-1,
Mixing time is 20 ~ 40min.Preferably, mixing described in S5 uses mechanical agitation, and rotating speed is 300 ~ 500 rmin-1, during stirring
Between be 6 ~ 20h.
Preferably, cleaning solution used is washed described in S6 for deionized water or/and hydrochloric acid, is washed 3 ~ 5 times altogether.
Preferably, washing described in S6 is to be washed with deionized 2 ~ 3 times respectively, with 5% salt acid elution 1 ~ 2 time.
Preferably, dried described in S6 as normal-temperature vacuum is dried, the drug bearing microsphere that will be prepared after drying is protected in 4 DEG C of lucifuges
Deposit.
Compared with prior art, the invention has the advantages that：
（1）Selenium-rich drug bearing microsphere of the present invention is located in advance with barium selenite as main ingredient by the ultrasonic disperse of barium selenite
Reason, ultrasonic disperse uses closed ultrasonic usually using ultrasonic probe, this method, by institute's ultrasonic disperse material addition closed container
Ultrasound is carried out, the unnecessary injury that material and solvent volatilization are caused when this method can be prevented effectively from ultrasonic disperse；It is molten in polyvinyl alcohol
A certain amount of NaCl is added in liquid, promotes microballoon to be formed by improving water phase osmotic pressure, reduced because dichloromethane volatilization is caused
Microsphere surface hole, be conducive to microballoon to reach more preferable slow release effect；And each of drug bearing microsphere is prepared by reasonably optimizing
Constituent content, using the coating technique of S/O/W, drug bearing microsphere is prepared into using emulsified solution volatility process, and its drugloading rate is high, and can
By controlling the rate of release of process regulation medicine, so as to reduce barium selenite usage amount, extend the action time of medicine,
The toxic and side effect of medicine is reduced, the curative effect of medicine is improved.
（2）Preparation method technological process of the present invention is simple, the average grain diameter of the selenium-rich drug bearing microsphere for preparing for 3.52 ~
20.34 μm, drugloading rate is 17.5 ~ 25.3%, and drugloading rate is big and reproducible.
（3）The main ingredient that the present invention is used is inorganic selenium barium selenite, and with low cost, toxicity is relatively low, and when being detained in vivo
Between it is long, therefore be prepared into drug bearing microsphere and be generalized to field of veterinary, have good social benefit and economic interests prospect.
（4）The lapping that the present invention is used is industrial injection grade polylactic acid PLA, and cost of material is cheap, and preparation is not required to
Special expensive equipment, technological process is simple, and drug bearing microsphere has good biocompatibility.
Brief description of the drawings
Fig. 1 schemes for the barium selenite drug bearing microsphere SEM of embodiment 1.
Fig. 2 schemes for the barium selenite drug bearing microsphere SEM of embodiment 2.
Fig. 3 is the external release profiles of barium selenite drug bearing microsphere of embodiment 2.
Fig. 4 schemes for the barium selenite drug bearing microsphere SEM of embodiment 3.
Fig. 5 is the external release profiles of barium selenite drug bearing microsphere of embodiment 3.
Fig. 6 schemes for the barium selenite drug bearing microsphere SEM of comparative example 1.
Fig. 7 schemes for the barium selenite drug bearing microsphere SEM of comparative example 2.
Fig. 8 schemes for the barium selenite drug bearing microsphere SEM of comparative example 3.
Fig. 9 schemes for the barium selenite drug bearing microsphere SEM of comparative example 4.
Figure 10 is the external release profiles of barium selenite drug bearing microsphere of comparative example 4.
Specific embodiment
The present invention is further elaborated on reference to Figure of description and specific embodiment.But embodiment is not to this
Invention is limited in any form.Unless stated otherwise, the reagent for using of the invention, method and apparatus are the art routine
Reagent, method and apparatus.
Embodiment 1
A kind of preparation method of novel selenium-enriched drug bearing microsphere, comprises the following steps：
S1. 1g barium selenites powder is micronized, in adding 2 ~ 6mL dichloromethane, ultrasonic disperse, ultrasonic power is
100W, jitter time is 30min；
S2. 1.2g polylactic acid PLAs are dissolved in 20 ~ 50mL dichloromethane, ultrasonic wave dispersion, ultrasonic power is 100W,
Jitter time is 3h, forms solution；
S3. the mixture that S1 is obtained is dispersed in solution described in S2, mechanical agitation, rotating speed is 15000 r
min-1, 30s is stirred, form emulsion；
S4. 0.6g polyvinyl alcohol is dissolved in 100 ~ 300mL water, adds 1.5 ~ 5gNaCl, heating is well mixed to be formed
Poly-vinyl alcohol solution；
S5. the emulsion that S3 is formed is added in poly-vinyl alcohol solution described in S4 again, mechanical agitation, rotating speed is 15000
r·min-1, 6h is stirred, form S/O/W type emulsions；
S6. the emulsion that stirring S5 is obtained makes dichloromethane volatilize, and solidifies balling-up, then be centrifuged through 8000rpm, deionized water
Washing 3 times, again with 5% salt acid elution 2 times, normal-temperature vacuum drying obtains the selenium-rich drug bearing microsphere, is kept in dark place in 4 DEG C；
Wherein, barium selenite is main ingredient；The polylactic acid molecule amount is 100000.
The particle diameter of the selenium-rich drug bearing microsphere for preparing is 5.23 ~ 20.04 μm, and drugloading rate is 20 ~ 25%, drug bearing microsphere
SEM is as shown in Figure 1.
Embodiment 2
A kind of preparation method of novel selenium-enriched drug bearing microsphere, comprises the following steps：
S1. 0.5g barium selenites powder is micronized, in addition 1 ~ 3mL dichloromethane, ultrasonic disperse, ultrasonic power
It is 200W, jitter time is 30min；
S2. 1g polylactic acid PLAs are dissolved in 12 ~ 40ml dichloromethane, mechanical agitation, rotating speed is 500 rmin-1, stir
The time is mixed for 20min, solution is formed；
S3. the mixture that S1 is obtained is dispersed in solution described in S2, mechanical agitation, rotating speed is 15000 r
min-1, 30s is stirred, form emulsion；
S4. 0.8 polyvinyl alcohol is dissolved in 100 ~ 300 water, adds 1.5 ~ 5gNaCl, heating is well mixed to form poly-
Glycohol solution；
S5. the emulsion that S3 is formed is added in poly-vinyl alcohol solution described in S4 again, ultrasonic wave dispersion, ultrasonic power
It is 100W, disperses 3h, forms S/O/W type emulsions；
S6. the emulsion that stirring S5 is obtained makes dichloromethane volatilize, and solidifies balling-up, then be centrifuged through 8000rpm, deionized water
Washing 1 time, again with 5% salt acid elution 2 times, normal-temperature vacuum drying obtains the selenium-rich drug bearing microsphere, is kept in dark place in 4 DEG C；
Wherein, barium selenite is main ingredient；The polylactic acid molecule amount is 100000.
The particle diameter of the selenium-rich drug bearing microsphere for preparing is 6.48 ~ 18.45 μm, and drugloading rate is 21 ~ 25%, drug bearing microsphere
SEM is as shown in Figure 2.
The upper selenium-rich drug bearing microsphere is carried out into conventional vitro drug release test experiments, the present embodiment barium selenite is carried
Medicine microballoon is in acid release liquid（0.1MHC）In drug release rate it is shallower, after 24h release rate be 5%, and after 69d discharge
Rate is 10%.In neutral buffer（PH value is 7.4 PBS）In drug release rate it is substantially slow, 24h
Release rate is 3% afterwards, and release rate is 5.9% after 69d.Result is as shown in Figure 3.
Embodiment 3
A kind of preparation method of novel selenium-enriched drug bearing microsphere, comprises the following steps：
S1. 0.8g barium selenites powder is micronized, in addition 1.5 ~ 5mL dichloromethane, ultrasonic disperse, ultrasonic wave work(
Rate is 150W, and jitter time is 30min；
S2. 1.5g polylactic acid PLAs are dissolved in 12 ~ 40ml dichloromethane, mechanical agitation, rotating speed is 350 rmin-1,
Mixing time is 30min, forms solution；
S3. the mixture that S1 is obtained is dispersed in solution described in S2, mechanical agitation, rotating speed is 10000 r
min-1, 50s is stirred, form emulsion；
S4. 0.8g polyvinyl alcohol is dissolved in 100 ~ 300mL water, adds 2 ~ 6gNaCl, heating is well mixed to form poly-
Glycohol solution；
S5. the emulsion that S3 is formed is added in poly-vinyl alcohol solution described in S4 again, ultrasonic wave dispersion, ultrasonic power
It is 100W, disperses 2.5h, forms S/O/W type emulsions；
S6. the emulsion that stirring S5 is obtained makes dichloromethane volatilize, and solidifies balling-up, then is centrifuged through 8000rpm, through 5% hydrochloric acid
Washing 4 times, normal-temperature vacuum is dried, and obtains the selenium-rich drug bearing microsphere, is kept in dark place in 4 DEG C；
Wherein, barium selenite is main ingredient；The polylactic acid molecule amount is 100000.
The particle diameter of the selenium-rich drug bearing microsphere for preparing is 4.63 ~ 20.18 μm, and drugloading rate is 20.47 ~ 24.26%, carries medicine
The SEM of microballoon is as shown in Figure 4.
Above-mentioned drug bearing microsphere is carried out into conventional vitro drug release test experiments, the present embodiment barium selenite drug bearing microsphere
In acid release liquid（0.1MHC）In drug release rate it is shallower, release rate is 7.4% after 24h, and release rate is after 300h
15.9%.In neutral buffer（PH value is 7.4 PBS）In drug release rate it is substantially slow, after 24h
Release rate is 3.7%, and release rate is 6.3% after 300h.Result is as shown in Figure 5.
Comparative example 1
This comparative example is essentially identical with the preparation method that embodiment 3 prepares selenium-rich drug bearing microsphere, and difference is that this is right
Ratio is to the processing method of the S1 steps：Treatment 1. -0.8g barium selenite powder is micronized for subsequent step, without Asia
Barium selenate it is ultrasonically treated；Treatment 2.-by 0.8g barium selenites powder micronizing, add 0.5 ~ 1mL dichloromethane in, ultrasound point
Dissipate, ultrasonic power is 70W, and jitter time is 40min.
The particle diameter of selenium-rich drug bearing microsphere that 1. treatment prepares is 3.04 ~ 36.89 μm, drugloading rate is 9.17% ~
13.43%；The particle diameter of selenium-rich drug bearing microsphere that 2. treatment prepares is 4.08 ~ 30.47 μm, drugloading rate is 11.46% ~
15.95%.1. with treatment 2. to barium selenite without pre-processing or dealing with improperly, influence barium selenite particle is in colostrum for treatment
Deployment conditions, and then the reaction of prepared oil phase and barium selenite is influenceed, cause coating microspherulite diameter uneven, drugloading rate drop
Low, drug loss rate is improved, and the SEM of drug bearing microsphere is as shown in Figure 6.
Comparative example 2
This comparative example is essentially identical with the preparation method that embodiment 3 prepares selenium-rich drug bearing microsphere, and difference is that this is right
Ratio is to the processing method of the S4 steps：Treatment 1.-will without the poly-vinyl alcohol solution of NaCl be used for subsequent step；Place
Reason 2. -0.3g polyvinyl alcohol is dissolved in 100 ~ 300mL water, add 0.5gNaCl, heating is well mixed to form polyvinyl alcohol
Solution.
The particle diameter of selenium-rich drug bearing microsphere that 1. treatment prepares is 5.89 ~ 18.46 μm, drugloading rate is 10.89 ~
13.12%；The particle diameter of the selenium-rich drug bearing microsphere that 2. treatment prepares is 4.56 ~ 20.03 μm, and drugloading rate is 12.72 ~ 16.47%,
Treatment can influence the osmotic pressure of water phase and oil phase 1. with treatment 2. to being not added with salt in water phase or adding concentration not in proper range,
The change of system osmotic pressure causes the water in water phase to flow into oil phase, and the hole left in microballoon formation stages microsphere surface is exactly water
By water mutually into the proof of oil phase, microsphere surface hole is more more more is unfavorable for playing slow release effect, SEM such as Fig. 7 of drug bearing microsphere
It is shown.
Comparative example 3
This comparative example is essentially identical with the preparation method that embodiment 3 prepares selenium-rich drug bearing microsphere, and difference is that this is right
Ratio is to the processing method of the S2 steps：The molecular weight for processing 1.-polylactic acid PLA is 50000；Treatment 2.-it is described
The molecular weight of polylactic acid PLA is 150000.
The particle diameter of the selenium-rich drug bearing microsphere that 1. treatment prepares is 2.13 ~ 13.79 μm, and drugloading rate is 8.78 ~ 10.16%；
The particle diameter of the selenium-rich drug bearing microsphere that 2. treatment prepares is 7.46 ~ 40.15 μm, and drugloading rate is 4.17% ~ 9.72%.Treatment 1. with
When 2. treatment prepares microballoon using low-molecular-weight and HMW PLA respectively, the smaller viscosity of mixed liquid of molecular weight of PLA diminishes,
Microspherulite diameter is formed in the case of high dispersive power smaller, cause drugloading rate to reduce；The molecular weight of PLA is bigger or concentration is more high all
Can cause, viscosity is excessive in mixed liquor, in the case where dispersion force is inadequate, it is difficult to balling-up, cause relatively low drugloading rate and encapsulating
Rate, the SEM of drug bearing microsphere is as shown in Figure 8.
Comparative example 4
A kind of preparation method of novel selenium-enriched drug bearing microsphere, comprises the following steps：
S1. 0.8g barium selenites powder is micronized, in addition 3 ~ 5ml dichloromethane, ultrasonic disperse, ultrasonic power
It is 150W, jitter time is 30min；
S2. 2.5g polylactic acid PLAs are dissolved in 10ml dichloromethane, mechanical agitation, rotating speed is 350 rmin-1, stirring
Time is 30min, forms solution；
S3. the mixture that S1 is obtained is dispersed in solution described in S2, mechanical agitation, rotating speed is 10000 r
min-1, 50s is stirred, form emulsion；
S4. 1.5 polyvinyl alcohol are dissolved in 100 ~ 200 water, add 1 ~ 4gNaCl, heating is well mixed to form poly- second
Enolate solution；
S5. the emulsion that S3 is formed is added in poly-vinyl alcohol solution described in S4 again, ultrasonic wave dispersion, ultrasonic power
It is 100W, disperses 2.5h, forms S/O/W type emulsions；
S6. the stirring emulsions that obtain of S5 make dichloromethane volatilize, and solidify balling-up, then are centrifuged through 8000rpm, through go for 1 time from
Sub- water washing and 1 5% salt acid elution, normal-temperature vacuum are dried, and obtain the selenium-rich drug bearing microsphere, are kept in dark place in 4 DEG C；
Wherein, barium selenite is main ingredient；The polylactic acid molecule amount is 100000.
The particle diameter of the selenium-rich drug bearing microsphere for preparing is 5.04 ~ 41.17 μm, and drugloading rate is 7.15 ~ 10.46, carries medicine micro-
The SEM of ball is as shown in Figure 9.
Above-mentioned drug bearing microsphere is carried out into conventional vitro drug release test experiments, this comparative example barium selenite drug bearing microsphere
In acid release liquid（0.1MHCL）In drug release rate it is shallower, after 24h release rate be 18.35%, and after 300h discharge
Rate is 28.15%.In neutral buffer（PH value is 7.4 PBS）In drug release rate it is substantially slow,
Release rate is 13.27% after 24h, and release rate is 17.98% after 300h, as a result as shown in Figure 10.
Claims (8)
1. a kind of preparation method of novel selenium-enriched drug bearing microsphere, it is characterised in that comprise the following steps：
S1. 1 ~ 8 part of barium selenite powder is micronized, in adding 10 ~ 25 parts of dichloromethane, ultrasonic disperse, ultrasonic power is
100 ~ 200W, jitter time is 30min；
S2. 4 ~ 12 parts of PLAs are dissolved in 100 ~ 300 parts of dichloromethane, it is well mixed to form solution；
S3. the mixture that S1 is obtained is dispersed in solution described in S2, it is well mixed to form emulsion；
S4. 1 ~ 100 part of polyvinyl alcohol is dissolved in 1000 ~ 5000 parts of water, adds 20 ~ 100 parts of NaCl, heating is well mixed
Form poly-vinyl alcohol solution；
S5. the emulsion that S3 is formed is added in poly-vinyl alcohol solution described in S4 again, it is well mixed to form S/O/W type emulsions；
S6. the emulsion that stirring S5 is obtained makes dichloromethane volatilize, and solidifies balling-up, then through being centrifuged, washing, dry, obtain the richness
Selenium drug bearing microsphere；
Wherein, barium selenite is main ingredient；The polylactic acid molecule amount is 100000；
The number of the barium selenite, dichloromethane, PLA, polyvinyl alcohol, NaCl and water is parts by weight.
2. preparation method according to claim 1, it is characterised in that the average grain diameter of the selenium-rich drug bearing microsphere for preparing
It is 3.52 ~ 20.34 μm.
3. preparation method according to claim 2, it is characterised in that the drugloading rate of the selenium-rich drug bearing microsphere for preparing is
17.5~25.3%。
4. preparation method according to claim 1, it is characterised in that mix described in S3 using ultrasonic wave dispersion, ultrasonic wave
Power is 100W, and jitter time is 1 ~ 3h.
5. preparation method according to claim 1, it is characterised in that mixing described in S3 uses mechanical agitation, and rotating speed is
5000~15000 r·min-1, mixing time is 30s ~ 1min.
6. preparation method according to claim 1, it is characterised in that it is deionized water that cleaning solution used is washed described in S6
Or/and hydrochloric acid, wash 3 ~ 5 times altogether.
7. preparation method according to claim 6, it is characterised in that washing described in S6 to be washed with deionized 2 respectively ~
3 times, with 5% salt acid elution 1 ~ 2 time.
8. preparation method according to claim 1, it is characterised in that it is that normal-temperature vacuum is dried to be dried described in S6, after drying
The drug bearing microsphere that will be prepared keeps in dark place in 4 DEG C.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510099844.0A CN104688692B (en) | 2015-03-06 | 2015-03-06 | A kind of preparation method of novel selenium-enriched drug bearing microsphere |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510099844.0A CN104688692B (en) | 2015-03-06 | 2015-03-06 | A kind of preparation method of novel selenium-enriched drug bearing microsphere |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104688692A CN104688692A (en) | 2015-06-10 |
| CN104688692B true CN104688692B (en) | 2017-06-20 |
Family
ID=53336526
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510099844.0A Active CN104688692B (en) | 2015-03-06 | 2015-03-06 | A kind of preparation method of novel selenium-enriched drug bearing microsphere |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104688692B (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| 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 |
| 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 |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2201237C2 (en) * | 2001-05-23 | 2003-03-27 | Закрытое акционерное общество Научно-производственное предприятие "Агрофарм" | Preparation for prophylaxis and treatment of selenium deficiency in agricultural animals and method of its preparing |
| WO2007130575A2 (en) * | 2006-05-03 | 2007-11-15 | Florida Atlantic University | Protection against oxidative damage in cells |
| CN102603396B (en) * | 2011-12-27 | 2014-12-03 | 辽宁师范大学 | Preparation of chitosamine-selenium nanometer trace-element nutrition regulator |
-
2015
- 2015-03-06 CN CN201510099844.0A patent/CN104688692B/en active Active
Non-Patent Citations (1)
| Title |
|---|
| 亚硒酸钡聚乳酸微球的制备及其体内释放特性研究;陈妍召 等;《2013年中国畜牧兽医学会兽医药理学分会第十二次学术讨论会》;20040901;"目的"部分 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN104688692A (en) | 2015-06-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE60106666T2 (en) | Continuous process for the preparation of sustained-release microcapsules of water-soluble peptides | |
| CN104688692B (en) | A kind of preparation method of novel selenium-enriched drug bearing microsphere | |
| CN100452984C (en) | Aimal growth regulating composition and its prepn and use | |
| WO2009101132A1 (en) | Combination of vitamin d and 25-hydroxyvitamin d 3 | |
| CN107595809A (en) | A kind of zeins nanometer embedding sustained release filler and preparation method thereof | |
| CN107007875A (en) | A kind of enzyme carries liquid medicine gel and preparation method and application with temperature double responsiveness | |
| KR20200132584A (en) | Stabilized astaxanthin nanoparticles and its manufacturing method | |
| CN1927188A (en) | Voltage endurance vitamin E microcapsule and its preparing process | |
| CN1239150C (en) | Nano grade vitamin micro emulsion and its preparing method | |
| CN1380056A (en) | Preparation method of high-content oil-soluble vitamin slow-releasing microcapsule powder | |
| CN102552328A (en) | Preparation method of compound fish oil nano-emulsion | |
| CN104997794B (en) | A kind of long-acting multi-vitamins oral latex emulsion for animals and preparation method thereof | |
| CN100518730C (en) | Novel Subing drop pills and preparation method | |
| KR100871050B1 (en) | Preparation method of microcapsule comprising coenzyme Q1O | |
| CN1679609A (en) | Compound energy mistura fat-soluble vitamins adult preparation and use thereof | |
| CN1286514C (en) | Compound rose essential oil soft capsule and its preparation method | |
| CN1732903A (en) | Method for preparing sustained-release miniball | |
| CN1193761C (en) | Controllable release system of glucocorticoid and its preparation and use | |
| CN1853634A (en) | Composition comprising itraconazole for oral administration | |
| CN1565428A (en) | Chitosan microcapsule and its preparation method and uses | |
| CN1850270A (en) | Ovotransferrin iron supplement agent, and its preparing method and use | |
| CN1278676C (en) | Curcumin injection and method for preparing the same | |
| CN105287629B (en) | A kind of preparation method and its pharmaceutical usage of animal unnairing therapeutic agent | |
| JPS5849433A (en) | Production of microcapsule | |
| CN1781486A (en) | Composite amino acid and vitamine capsule preparation and its preparing method |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |