CN108912349A - Polylactic acid microsphere and preparation method thereof and the application in medicament slow release - Google Patents
Polylactic acid microsphere and preparation method thereof and the application in medicament slow release Download PDFInfo
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Abstract
The invention discloses a kind of polylactic acid microsphere, preparation method is：By oil-soluble magnetic Fe3O4Nano particle is added in the chloroformic solution of polylactic acid, is added or is added without drug, and the aqueous solution of carboxyetbyl chitosan is added, and emulsifier is added, and ultrasonic disperse is warming up to 45~55 DEG C, and initiator is added and causes polymerization；After reaction, vacuum distillation remove chloroform, microballoon is collected by centrifugation, and washed with distilled water ultrasound suspending, be collected by centrifugation to get.Polylactic acid microsphere prepared by the present invention can be used for preparing slow releasing pharmaceutical, and drugloading rate is high, and the shell of microballoon is chitosan, and kernel is polylactic acid, and for drug distribution in polylactic acid, slow release effect is significant.In addition, present invention further introduces magnetic Fes3O4Nano particle imparts microballoon MR imaging effect, and can issue thermal property in specific magnetic fields environment using magnetic nanoparticle, the release for keeping the available repetition of drug of package controllable.
Description
Technical field
The present invention relates to a kind of novel polylactic acid microsphere, and preparation method thereof, and the application in medicament slow release.
Background technique
When drug therapy disease, other than needing to consider its therapeutic effect, it is also necessary to consider its concentration and dimension in vivo
Hold time, absorption excretion in vivo and to toxic side effect of human body etc..Drug concentration is excessively high, can generate not to the health of human body
Benefit influences, and drug concentration is too low cannot play expected effect.Traditional pharmaceutical preparation can discharge rapidly after entering human body
Drug out makes the drug concentration in blood quickly reach maximum, and decline rapidly again, causes most of drug with blood later
Absorbed organ, metabolism and the excretion passed through in flow process, only a small amount of drug reach desired location.Therefore patient is necessary
Multiple overdose drug can be only achieved expected therapeutic effect, this had not only caused the waste of drug, but also result in the secondary work of various poison
Generation.It can be seen that traditional pharmaceutical preparation can no longer meet people to the medical science and health of continuous development
It is required that novel drug controlled release Transmission system (Controlled Release Drug Delivery System) has become
For the hot spot of current pharmaceutical preparation research.
Common drug controlled release transmission platform has the forms such as liposome, polymer microballoon, Submicron Emulsion, micro emulsion, micella,
Wherein liposome and polymer microballoon are two kinds of forms of most important one, and polymer microballoon is because of the stability of its own
And become the primary selection of controlled release drug delivery system to the controllability of institute's carrying medicament release mode.It is micro- before 70 years
Encapsulated technology is used to come for the first time, and modern microencapsulation drug has evolved into important pharmaceutical dosage form.The partial size of microballoon is big
It is small from several nanometers to hundreds of microns, can be by including injection (intravenous injection, intramuscular injection), oral, nose drop, subdermal implantation
Etc. number of ways administration, meet different requirements.
Polymer microballoon drug controlled release Transmission system require carrier material it is non-toxic to humans, not with encapsulated
Drug reacts, and the release of drug not only may be implemented, and can also control release time, rate of release.It is higher
It is required that being that can carry out the drug release (target delivery) of appointed part and be released the drug according to the variation of external environment
Deng.These functions enable novel drug controlled release Transmission system to reach saving medication, improve curative effect, reduce toxic side effect
And the purpose for the treatment of is accurately controlled.
Polylactic acid (polylactic acid or polylactide, PLA) be using fast-growing resource corn as primary raw material,
Fermented obtained lactic acid, then the polymer obtained with lactic acid for main polymerizable raw material.Polylactic acid is due to compatible with good biological
Property and biological degradability, catabolite can participate in the metabolism of human body and performance can in a wide range of by with other monomers
Copolymerization is adjusted, it has also become one of most valued material in current biological medical domain.The hydrolysis final product of PLA is water
And carbon dioxide, intermediate product lactic acid are also intracorporal eubolism product, no physiological activity, irritation is small, easily from internal row
It is undegradable to be discharged with excrement out without accumulating, avoid the secondary injury caused by patient.Histological research proves：
PLA is nontoxic, and reactionless with tissue, biodegradable, catabolite is not stranded in living tissue.With poly lactic-co-glycolic acid
(PLGA) since preparing progesterone PLGA spansule for capsule material, PLA and its copolymer are used as some half-life shorts, stability
Poor, degradable and big toxic side effect medicine controlled release carrier, such as antibiotic, anticancer medication, vaccine, hormone, family planning medication, antipyretic
The slow controlled release carrier of antalgesic and nervous system medication etc. can effectively increase administration route, reduce administration number of times and dosage,
Drug availability is improved, side effect of the drug to liver, kidney etc. is reduced.
Recent domestic has studies have shown that PLA is applied to controlled drug delivery system and extends drug treating time,
The advantages that improving directionality and reducing toxic side effect, thus have good development prospect.Currently, PLA and its copolymer analog sustained release
What preparation had been commercialized has luteinising hormone-releasing hormo LHRH class drug Goserelin subcutaneous implant, Leuprorelin muscle note
Penetrate suspension, thyrotropin-releasing hormone (TRH) TRH class drug Triptorelin, antibiotic oxacillin etc..The medicine studied
There are many object, mainly there is anticancer chemotherapy medication, analgesic-antipyretic, nervous system medication, hormone and family planning medication etc., all in
Laboratory research or animal experiment stage.In addition, can be made into specific according to the property of drug, release request and administration route
Pharmaceutical dosage form.Better simply to prepare implant preparation using the methods of solution molding, hot-forming, the PLGA bilayer such as insulin is slow
Release the hollow of piece, the PLA cylindrical body of gentamicin, the blocky implant of growth-promoting object hormone releasing hormone and the left rhymed formula promise ketone of hormone
PLA fiber dosage form etc., in addition there are a variety of dosage forms such as film, pores agent, its geometry of all strong dependence of these dosage forms and
Drug encapsulation amount.
It treats diagnostic techniques and refers to the technology for combining medical diagnosis and treatment, these medical diagnosis such as ultrasonic (US), magnetic are total
Vibration (MR), x-ray tomography (CT) imaging technique etc.；Treatment means include chemotherapy, radiotherapy, thermotherapy etc..This combine for
The specificity and adaptability of cancer are of great significance, and this combines the research also expedited the emergence of to novel treatment diagnosticum.
Extensive use with chemotherapy and diagnosis using complementary type as cancer diagnosis and treatment clinically, the treatment diagnosticum based on chemotherapy will
Hot spot as medical imaging research.
Summary of the invention
For the above-mentioned prior art, the present invention provides a kind of novel polylactic acid microsphere, and preparation method thereof, Yi Ji
Application in medicament slow release.
The present invention is achieved by the following technical solutions：
A kind of preparation method of polylactic acid microsphere：By the oil-soluble magnetic Fe of 0.2~0.5mg3O4Nano particle is added to
In the chloroformic solution of 5ml polylactic acid, the aqueous solution of 50ml carboxyetbyl chitosan is added, 0.04~0.06g emulsifier, ultrasound is added
Dispersion 10 minutes, is warming up to 45~55 DEG C, be added 0.8~1.2mg initiator (by etc. quality K2S2O8And NaHSO3Composition)
Cause polymerization, reacts 6~10 hours；After reaction, vacuum distillation removes chloroform, microballoon is collected by centrifugation, and super with distilled water
Acoustic levitation washing is collected by centrifugation 3 times to get freeze-drying is stored under the conditions of 4 DEG C.When preparing drug bearing microsphere, by 20mg's
Drug (such as felodipine) is dissolved in the chloroformic solution of polylactic acid, remaining step is identical.
The carboxyetbyl chitosan can be prepared by a conventional method to obtain, such as：Acrylic acid solution is taken, hydroxide is added
It is 6.5~7.5 that sodium solution, which adjusts pH, obtains mixed solution；By 1.5~3g chitosan (food-grade, 100 mesh, deacetylation 90%)
It is added in three-necked flask, 50ml mixed solution is added, and (mass ratio of acrylic acid and chitosan is 3.5~4.5:1), in 90 DEG C of water
It is reacted 4~6 hours under the conditions of bath；It after reaction, is 9~10 with sodium hydroxide solution adjustment pH, supernatant is collected in centrifugation,
95% ethyl alcohol that three times volume is added is precipitated, and twice, dehydrated alcohol washing is filtered, is dried in vacuo to get carboxyethyl precipitating
Chitosan.
The emulsifier is selected from polyvinyl alcohol, and sulfosuccinic acid double tridecyl ester sodium (BASDE), additional amount is preferred
0.05g。
The concentration of the polylactic acid is 0.01~0.03g/ml, preferably 0.02g/ml.
The concentration of the aqueous solution of the carboxyetbyl chitosan is 0.002~0.006g/ml, preferably 0.005g/ml.
The parameter that microballoon is collected by centrifugation is：15000rpm is centrifuged 30 minutes.
Polylactic acid microsphere prepared by the present invention, partial size about 500nm can be used for preparing slow releasing pharmaceutical, and drugloading rate is high, microballoon
Shell is chitosan, and kernel is polylactic acid, and drug distribution is in polylactic acid, when drug release, due to depositing between dissolution medium
In concentration difference, drug passes through the gap of microsphere surface to external diffusion, moreover, because dewatering medicament and polylactic acid generation are hydrophobic mutually
Effect, can be effectively reduced the rate of release of drug, slow release effect is significant.In addition, present invention further introduces magnetic Fes3O4Nanometer
Particle imparts microballoon MR imaging effect, and can issue thermal property in specific magnetic fields environment using magnetic nanoparticle, makes
The controllable release of the available repetition of the drug of package has wide application in treatment diagnostic techniques.
Oil containing polylactic acid is mutually distributed to by the preparation method of polylactic acid microsphere of the invention by ultrasonic disperse effect
In carboxyetbyl chitosan aqueous solution containing emulsifier.On the one hand, contain hydrophobic grouping in carboxyetbyl chitosan molecular structure,
The presence of these hydrophobic groups has to be adsorbed on the O/W drop containing polylactic acid conducive to carboxyetbyl chitosan, so as to effectively
Reduce oil-water interfaces free energy；On the other hand, since carboxyetbyl chitosan molecule has biggish volume, and there is part carboxyl
Dissociation, therefore the carboxyetbyl chitosan being adsorbed can further decrease oil by steric hindrance and electrostatic repulsion synergistic effect again
Water termination free energy keeps lotion more stable.Under the initiation of redox initiator, it is adsorbed on the carboxyethyl shell of oil droplets
Glycan occurs polymerization and forms the microballoon shell of cross-linked structure, and the oil of the oil phase drop containing polylactic acid or the polylactic acid containing drug
Phase droplet formation microballoon core.Finally, removing the oily phase chloroform in microballoon using the method for solvent evaporation, obtains and crosslink carboxyethyl
The microballoon for not carrying medicine and carrying medicine that chitosan is hydrophilic shell, polylactic acid is hydrophobic core.
Specific embodiment
Below with reference to embodiment, the present invention is further illustrated.However, the scope of the present invention is not limited to following realities
Apply example.One of skill in the art, can be to the present invention it is understood that under the premise of without departing substantially from the spirit and scope of the present invention
Carry out various change and modification.
Instrument involved in following embodiments, reagent, material etc. are unless otherwise noted existing in the prior art
Conventional instrument, reagent, material etc., can be obtained by regular commercial sources.Experimental method involved in following embodiments, inspection
Survey method etc. is unless otherwise noted existing routine experiment method in the prior art, detection method etc..
Embodiment 1 prepares polylactic acid microsphere (not carrying medicine)
By the oil-soluble magnetic Fe of 0.4mg3O4Nano particle is added to the chloroformic solution (concentration of polylactic acid of 5ml polylactic acid
For in 0.02g/ml), 0.05g emulsifier is added in the aqueous solution (concentration 0.005g/ml) of addition 50ml carboxyetbyl chitosan,
Ultrasonic disperse 10 minutes, be warming up to 50 DEG C, be added 1mg initiator (by etc. quality K2S2O8And NaHSO3Composition) cause and gathers
It closes, reacts 8 hours；After reaction, vacuum distillation remove chloroform, 15000rpm be centrifuged 30 minutes, collect microballoon, and with distill
The washing of water ultrasound suspending is collected by centrifugation 3 times to get freeze-drying is stored under the conditions of 4 DEG C.
When preparing drug bearing microsphere, the drug (such as felodipine) of 20mg is dissolved in the chloroformic solution of polylactic acid,
Remaining step is identical.
The carboxyetbyl chitosan is prepared by the following method to obtain：Acrylic acid solution is taken, sodium hydroxide solution tune is added
Whole pH is 7, obtains mixed solution；2g chitosan (food-grade, 100 mesh, deacetylation 90%) are added in three-necked flask, are added
(mass ratio of acrylic acid and chitosan is 4 to 50ml mixed solution:1) it, is reacted 5 hours under 90 DEG C of water bath conditions；Reaction terminates
It afterwards, is 10 with sodium hydroxide solution adjustment pH, supernatant is collected in centrifugation, and 95% ethyl alcohol that three times volume is added is precipitated, and is sunk
It forms sediment twice, dehydrated alcohol washing is filtered, is dried in vacuo to get carboxyetbyl chitosan.
The emulsifier is sulfosuccinic acid double tridecyl ester sodium (BASDE).
Embodiment 2 prepares polylactic acid microsphere (carrying medicine)
By the oil-soluble magnetic Fe of 0.4mg3O4Nano particle is added to the chloroformic solution (concentration of polylactic acid of 5ml polylactic acid
For the drug (felodipine) that 20mg in 0.02g/ml), is added, the aqueous solution of 50ml carboxyetbyl chitosan is added, and (concentration is
0.005g/ml), be added 0.05g emulsifier, ultrasonic disperse 10 minutes, be warming up to 50 DEG C, be added 1mg initiator (by etc. quality
K2S2O8And NaHSO3Composition) cause polymerization, it reacts 8 hours；After reaction, vacuum distillation remove chloroform, 15000rpm from
The heart 30 minutes, microballoon is collected, and washed with distilled water ultrasound suspending, be collected by centrifugation 3 times to get freeze-drying is stored in 4 DEG C
Under the conditions of.
The carboxyetbyl chitosan is prepared by the following method to obtain：Acrylic acid solution is taken, sodium hydroxide solution tune is added
Whole pH is 7, obtains mixed solution；2g chitosan (food-grade, 100 mesh, deacetylation 90%) are added in three-necked flask, are added
(mass ratio of acrylic acid and chitosan is 4 to 50ml mixed solution:1) it, is reacted 5 hours under 90 DEG C of water bath conditions；Reaction terminates
It afterwards, is 10 with sodium hydroxide solution adjustment pH, supernatant is collected in centrifugation, and 95% ethyl alcohol that three times volume is added is precipitated, and is sunk
It forms sediment twice, dehydrated alcohol washing is filtered, is dried in vacuo to get carboxyetbyl chitosan.
The emulsifier is sulfosuccinic acid double tridecyl ester sodium (BASDE).
The polylactic acid microsphere of above-mentioned preparation, partial size about 500nm, drugloading rate is high, and the shell of microballoon is chitosan, and kernel is poly-
Lactic acid, drug distribution is in polylactic acid, when drug release, since, there are concentration difference, drug passes through microballoon between dissolution medium
Drug can be effectively reduced moreover, because hydrophobic interaction occurs for dewatering medicament and polylactic acid to external diffusion in the gap on surface
Rate of release, slow release effect is significant.In addition, also introducing magnetic Fe3O4Nano particle imparts microballoon MR imaging effect, and
Thermal property can be issued in specific magnetic fields environment using magnetic nanoparticle, keep the available repetition of drug of package controllable
Release.
Embodiment 3 prepares polylactic acid microsphere (not carrying medicine)
By the oil-soluble magnetic Fe of 0.4mg3O4Nano particle is added to the chloroformic solution (concentration of polylactic acid of 5ml polylactic acid
For the aqueous solution (concentration 0.006g/ml) of 50ml carboxyetbyl chitosan is added in 0.01g/ml), it is poly- that 0.06g emulsifier is added
Vinyl alcohol ultrasonic disperse 10 minutes, is warming up to 50 DEG C, be added 0.8mg initiator (by etc. quality K2S2O8And NaHSO3Group
At) cause polymerization, it reacts 10 hours；After reaction, vacuum distillation removes chloroform, and 15000rpm is centrifuged 30 minutes, collects micro-
Ball, and washed with distilled water ultrasound suspending, be collected by centrifugation 3 times to get freeze-drying is stored under the conditions of 4 DEG C.
The carboxyetbyl chitosan is prepared by the following method to obtain：Acrylic acid solution is taken, sodium hydroxide solution tune is added
Whole pH is 7, obtains mixed solution；1.5g chitosan (food-grade, 100 mesh, deacetylation 90%) are added in three-necked flask, are added
(mass ratio of acrylic acid and chitosan is 3.5 to 50ml mixed solution:1) it, is reacted 6 hours under 90 DEG C of water bath conditions；Reaction knot
Shu Hou is 10 with sodium hydroxide solution adjustment pH, and supernatant is collected in centrifugation, and 95% ethyl alcohol that three times volume is added is precipitated,
Twice, dehydrated alcohol washing is filtered, is dried in vacuo to get carboxyetbyl chitosan precipitating.
Embodiment 4 prepares polylactic acid microsphere (carrying medicine)
By the oil-soluble magnetic Fe of 0.4mg3O4Nano particle is added to the chloroformic solution (concentration of polylactic acid of 5ml polylactic acid
For the anticancer drug of 20mg in 0.01g/ml), is added, aqueous solution (the concentration 0.006g/ of 50ml carboxyetbyl chitosan is added
Ml), be added 0.06g emulsifier polyvinyl alcohol, ultrasonic disperse 10 minutes, be warming up to 50 DEG C, be added 0.8mg initiator (by etc.
The K of quality2S2O8And NaHSO3Composition) cause polymerization, it reacts 10 hours；After reaction, vacuum distillation removes chloroform,
15000rpm is centrifuged 30 minutes, collects microballoon, and wash with distilled water ultrasound suspending, be collected by centrifugation 3 times to get, be freeze-dried,
It is stored under the conditions of 4 DEG C.
The carboxyetbyl chitosan is prepared by the following method to obtain：Acrylic acid solution is taken, sodium hydroxide solution tune is added
Whole pH is 7, obtains mixed solution；1.5g chitosan (food-grade, 100 mesh, deacetylation 90%) are added in three-necked flask, are added
(mass ratio of acrylic acid and chitosan is 4.5 to 50ml mixed solution:1) it, is reacted 5 hours under 90 DEG C of water bath conditions；Reaction knot
Shu Hou is 9 with sodium hydroxide solution adjustment pH, and supernatant is collected in centrifugation, and 95% ethyl alcohol that three times volume is added is precipitated,
Twice, dehydrated alcohol washing is filtered, is dried in vacuo to get carboxyetbyl chitosan precipitating.
Embodiment 5 prepares polylactic acid microsphere (not carrying medicine)
By the oil-soluble magnetic Fe of 0.5mg3O4Nano particle is added to the chloroformic solution (concentration of polylactic acid of 5ml polylactic acid
For the aqueous solution (concentration 0.003g/ml) of 50ml carboxyetbyl chitosan is added in 0.03g/ml), it is poly- that 0.05g emulsifier is added
Vinyl alcohol ultrasonic disperse 10 minutes, is warming up to 50 DEG C, be added 1.2mg initiator (by etc. quality K2S2O8And NaHSO3Group
At) cause polymerization, it reacts 6 hours；After reaction, vacuum distillation removes chloroform, and 15000rpm is centrifuged 30 minutes, collects micro-
Ball, and washed with distilled water ultrasound suspending, be collected by centrifugation 3 times to get freeze-drying is stored under the conditions of 4 DEG C.
The carboxyetbyl chitosan is prepared by the following method to obtain：Acrylic acid solution is taken, sodium hydroxide solution tune is added
Whole pH is 7.5, obtains mixed solution；3g chitosan (food-grade, 100 mesh, deacetylation 90%) are added in three-necked flask, are added
(mass ratio of acrylic acid and chitosan is 3.5 to 50ml mixed solution:1) it, is reacted 6 hours under 90 DEG C of water bath conditions；Reaction knot
Shu Hou is 10 with sodium hydroxide solution adjustment pH, and supernatant is collected in centrifugation, and 95% ethyl alcohol that three times volume is added is precipitated,
Twice, dehydrated alcohol washing is filtered, is dried in vacuo to get carboxyetbyl chitosan precipitating.
Embodiment 6 prepares polylactic acid microsphere (carrying medicine)
By the oil-soluble magnetic Fe of 0.5mg3O4Nano particle is added to the chloroformic solution (concentration of polylactic acid of 5ml polylactic acid
For the drug (doxorubicin hydrochloride) that 20mg in 0.03g/ml), is added, the aqueous solution of 50ml carboxyetbyl chitosan is added, and (concentration is
0.003g/ml), 0.05g emulsifier polyvinyl alcohol is added, ultrasonic disperse 10 minutes, is warming up to 50 DEG C, the initiation of 1.2mg is added
Agent (by etc. quality K2S2O8And NaHSO3Composition) cause polymerization, it reacts 6 hours；After reaction, vacuum distillation removes dechlorination
Imitative, 15000rpm is centrifuged 30 minutes, collects microballoon, and is washed with distilled water ultrasound suspending, is collected by centrifugation 3 times to get freezing is dry
It is dry, it is stored under the conditions of 4 DEG C.
The carboxyetbyl chitosan is prepared by the following method to obtain：Acrylic acid solution is taken, sodium hydroxide solution tune is added
Whole pH is 7.5, obtains mixed solution；3g chitosan (food-grade, 100 mesh, deacetylation 90%) are added in three-necked flask, are added
(mass ratio of acrylic acid and chitosan is 4 to 50ml mixed solution:1) it, is reacted 4 hours under 90 DEG C of water bath conditions；Reaction terminates
It afterwards, is 10 with sodium hydroxide solution adjustment pH, supernatant is collected in centrifugation, and 95% ethyl alcohol that three times volume is added is precipitated, and is sunk
It forms sediment twice, dehydrated alcohol washing is filtered, is dried in vacuo to get carboxyetbyl chitosan.
Claims (10)
1. a kind of preparation method of polylactic acid microsphere, it is characterised in that：By the oil-soluble magnetic Fe of 0.2~0.5mg3O4Nanometer
Grain is added in the chloroformic solution of 5ml polylactic acid, is added or is added without drug, and the aqueous solution of 50ml carboxyetbyl chitosan is added,
0.04~0.06g emulsifier is added, ultrasonic disperse 10 minutes, is warming up to 45~55 DEG C, the initiator that 0.8~1.2mg is added draws
Hair polymerization, reacts 6~10 hours；After reaction, vacuum distillation removes chloroform, microballoon is collected by centrifugation, and ultrasonic with distilled water
Suspend washing, be collected by centrifugation 3 times to get.
2. the preparation method of polylactic acid microsphere according to claim 1, it is characterised in that：The carboxyetbyl chitosan leads to
Following methods are crossed to be prepared：Acrylic acid solution is taken, it is 6.5~7.5 that sodium hydroxide solution adjustment pH, which is added, obtains mixed solution；
1.5~3g chitosan is added in three-necked flask, is added 50ml mixed solution, the mass ratio of acrylic acid and chitosan is 3.5~
4.5:1, it is reacted 4~6 hours under 90 DEG C of water bath conditions；It after reaction, is 9~10 with sodium hydroxide solution adjustment pH, from
The heart collects supernatant, and 95% ethyl alcohol that three times volume is added is precipitated, and twice, dehydrated alcohol washing filters, vacuum precipitating
Drying is to get carboxyetbyl chitosan.
3. the preparation method of polylactic acid microsphere according to claim 1, it is characterised in that：The emulsifier is selected from poly- second
Enol, sulfosuccinic acid double tridecyl ester sodium, additional amount 0.05g.
4. the preparation method of polylactic acid microsphere according to claim 1, it is characterised in that：The concentration of the polylactic acid is
0.01~0.03g/ml.
5. the preparation method of polylactic acid microsphere according to claim 1, it is characterised in that：The water of the carboxyetbyl chitosan
The concentration of solution is 0.002~0.006g/ml.
6. the preparation method of polylactic acid microsphere according to claim 1, it is characterised in that：The initiator by etc. quality
K2S2O8And NaHSO3Composition.
7. the preparation method of polylactic acid microsphere according to claim 1, it is characterised in that：The ginseng that microballoon is collected by centrifugation
Number is：15000rpm is centrifuged 30 minutes.
8. the preparation method of polylactic acid microsphere according to any one of claims 1 to 7, it is characterised in that：By 0.4mg oil
The magnetic Fe of dissolubility3O4Nano particle is added in the chloroformic solution of 5ml polylactic acid, and the concentration of polylactic acid is 0.02g/ml, is added
The drug of 20mg is added without, and the aqueous solution of 50ml carboxyetbyl chitosan is added, and 0.05g emulsifier is added, and ultrasonic disperse 10 divides
Clock is warming up to 50 DEG C, and the initiator that 1mg is added causes polymerization, reacts 8 hours；After reaction, vacuum distillation removes chloroform,
15000rpm is centrifuged 30 minutes, collects microballoon, and wash with distilled water ultrasound suspending, be collected by centrifugation 3 times to get, be freeze-dried,
It is stored under the conditions of 4 DEG C.
9. the polylactic acid microsphere that any one of claim 1~8 preparation method is prepared.
10. application of the polylactic acid microsphere as claimed in claim 9 in medicament slow release.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110681323A (en) * | 2019-08-26 | 2020-01-14 | 上海摩漾生物科技有限公司 | Golf ball type degradable microsphere with micro-topological structure and preparation method thereof |
| CN112844340A (en) * | 2021-02-24 | 2021-05-28 | 毛星星 | Nano magnetic adsorbent with core-shell structure and preparation method thereof |
| CN113209372A (en) * | 2021-06-08 | 2021-08-06 | 青岛杰圣博生物科技有限公司 | Emulsification preparation method of polylactic acid soft tissue filling micro-rice grains |
| CN115354331A (en) * | 2022-08-22 | 2022-11-18 | 国网新疆电力有限公司电力科学研究院 | Metal corrosion-resistant slow-release microcapsule and preparation method and application thereof |
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2018
- 2018-05-29 CN CN201810531928.0A patent/CN108912349A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110681323A (en) * | 2019-08-26 | 2020-01-14 | 上海摩漾生物科技有限公司 | Golf ball type degradable microsphere with micro-topological structure and preparation method thereof |
| CN112844340A (en) * | 2021-02-24 | 2021-05-28 | 毛星星 | Nano magnetic adsorbent with core-shell structure and preparation method thereof |
| CN113209372A (en) * | 2021-06-08 | 2021-08-06 | 青岛杰圣博生物科技有限公司 | Emulsification preparation method of polylactic acid soft tissue filling micro-rice grains |
| CN115354331A (en) * | 2022-08-22 | 2022-11-18 | 国网新疆电力有限公司电力科学研究院 | Metal corrosion-resistant slow-release microcapsule and preparation method and application thereof |
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Application publication date: 20181130 |