CN103408784B - Method for controlling internal morphology of polylactic acid microspheres and polylactic acid microspheres prepared by same - Google Patents
Method for controlling internal morphology of polylactic acid microspheres and polylactic acid microspheres prepared by same Download PDFInfo
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Abstract
The invention provides a method capable of simply and efficiently controlling an internal structure of polylactic acid microspheres and belongs to the field of biologically degradable materials. The method is capable of controlling the internal structure of the polylactic acid microspheres by controlling the molecular weight of polylactic acid. Compared with the prior art, the method is better in operability in the aspect of controlling the internal structure of the polylactic acid microspheres; the method is simpler and more convenient; the method is capable of better regulating the release rate of drugs in the drug release aspect. The invention also provides polylactic acid microspheres prepared by the method.
Description
Technical field
The present invention relates to a kind of regulate and control the method for polylactic acid microsphere internal morphology, particularly, relating to a kind of method that molecular weight by controlling poly(lactic acid) regulates and controls polylactic acid microsphere internal morphology, also relating to the polylactic acid microsphere prepared by the method.
Background technology
Poly(lactic acid) (polylactic acid is called for short PLA) take lactic acid as monomer chemistries synthesis, and also claim polylactide, be have biodegradable polyphosphazene polymer ester material, its molecular formula is (C
3h
4o
2)
n.Poly(lactic acid) is that main raw material is polymerized the polymkeric substance obtained with lactic acid, and raw material sources are abundant and can regenerate.The production process of poly(lactic acid) is pollution-free, and product can biological degradation, and realizing the circulation at occurring in nature, is therefore desirable Green Polymer Material.
Microballoon, also known as microballoon capsule or micro-capsule, is a kind ofly utilize natural or synthesized polymer material for carrier parcel or absorption medicine and the spherical particulate of the spherical or class made.In recent years, poly(lactic acid) has been widely used in prepares microballoon, and described microballoon can be used for medicine carrying, and it is injected in human body, and in the process of people's body-internal-circulation, polylactic acid microsphere can be degraded, and medicine discharges thereupon, disease therapy.
The concrete pattern of microballoon can be divided into following three kinds:
(1) hollow structure, namely microballoon has a shell, and inside is hollow structure.If after such microballoon medicine carrying, medicine is concentrated in the space of hollow, shell is once decompose, and a large amount of medicines just discharges, the reason that Here it is " violent release ".
(2) many imitated vesicle structures, the i.e. inner hole having several aperture larger of microballoon, but number is few.
(3) vesicular structure, the i.e. inner hole having a lot of aperture very little of microballoon.Aperture is little, and quantity is many.
Clearly, the microballoon of these three kinds of structures is once after medicine carrying, and enter in human body and degrade, its release amount of medicine is different over time, and namely drug release profiles is different.According to different disease treatment requirements, required drug release profiles is also different.
Microballoon great majority utilize two/mono-emulsion method to prepare, and must use pore-creating agent, tensio-active agent and solid support material etc. in preparation process.
The method of now known control microballoon internal structure is main relevant with the control of technique with the selection of above-mentioned materials, such as: by changing the kind of tensio-active agent; The speed that is separated in microballoon process is being prepared by changing polymer carrier materials; By changing stir speed (S.S.); By changing the volume of interior aqueous phase, interior aqueous phase is now water, and it is as pore-creating agent; By changing the osmotic pressure of outer aqueous phase; By changing kind of polymer carrier materials etc.
A kind of method preparing poly(lactic acid) micron ball is reported in patent application CN102516565A.This invention utilizes a kind of dispersant with high efficiency, adopts solvent evaporation method to prepare the Polylactide Sustained Release Nanospheres of size tunable.The dispersant with high efficiency used is sulfo-succinic acid double tridecyl ester sodium, and the use of this dispersion agent overcomes the drawback that when using other tensio-active agent, consumption is too many.
A kind of preparation method of monodisperse polylactic acid microsphere is reported in patent application CN101392064A.Wherein relating generally to use micro passage reaction, by adjusting the flow velocity of disperse phase and external phase, generating the drop of size uniformity, after the solidification of this drop, just can obtain monodispersed polylactic acid microsphere.
Report a kind of by supercritical CO in patent application CN101036870A
2fluid prepares the method for polylactic acid microsphere.This invention shows that can regulate and control the particle diameter of microballoon within the specific limits, made microsphere average grain diameter is at 0.67-6.64 micron, and strength of solution and flow velocity are major influence factors by changing processing parameter; Experiment condition one timing, employing mixed solvent and Forced Dispersion solution method can prepare the microballoon compared with small particle size.
A kind of method preparing porous polylactic acid microball is reported in patent application CN1586704A.The method is with bad organic solvent for pore-creating agent, prepares porous polylactic acid microball with single emulsion method.
At present, wish to have a kind of method can control the internal structure of microballoon simply, efficiently, namely control the size and number of microballoon internal holes, to reach the object of Drug controlled release better.
the problem that invention will solve
The object of this invention is to provide a kind of method that can control the internal structure of polylactic acid microsphere simply, efficiently, can realize controlling the drug release in microballoon better.
for the scheme of dealing with problems
The invention provides a kind of regulate and control the method for polylactic acid microsphere internal morphology, comprise the following steps:
(1) synthesis of rac-Lactide
With D, Pfansteihl is raw material, under the temperature of reaction of-0.095MPa to the vacuum tightness of-0.085MPa and 170 DEG C to 195 DEG C, carries out polycondensation in the presence of a catalyst, obtains rac-Lactide crude product; Dissolved by rac-Lactide crude product, precipitation, obtains crystalline lactides, for subsequent use;
(2) synthesis of poly(lactic acid)
With the crystalline lactides of gained for raw material, under the existence of catalyzer and initiator, carry out polymerization and obtain poly(lactic acid);
(3) preparation of polylactic acid microsphere
Poly(lactic acid) being dissolved in by volume ratio is obtain PLA solution in the organic solvent that forms of the methylene dichloride of 9.5:0.5 ~ 8:2 and normal hexane, is then added drop-wise in polyvinyl alcohol water solution by PLA solution, solidify to form polylactic acid microsphere under magnetic stirring;
Be characterised in that: when poly(lactic acid) number-average molecular weight lower than 20000 time, obtain the microballoon of hollow structure; When poly(lactic acid) number-average molecular weight higher than 50000 time, obtain the microballoon of vesicular structure; When the number-average molecular weight of poly(lactic acid) is 20000-50000, obtain the microballoon of many imitated vesicle structures.
According to method of the present invention, be characterised in that, the catalyzer used in step (1) is zinc oxide.
According to method of the present invention, be characterised in that, in step (1) rac-Lactide crude product dissolved-precipitation by the method heating up-lower the temperature in ethyl acetate, obtain crystalline lactides.
According to method of the present invention, be characterised in that, by the mass ratio of rac-Lactide and initiator is controlled at rac-Lactide in step (2): initiator is 1:(0.00005 ~ 0.05), remain unchanged by making the amount of rac-Lactide, within the scope of aforementioned proportion, change the amount of initiator, polymerization obtains the poly(lactic acid) of different molecular weight.
According to method of the present invention, be characterised in that, the catalyzer used in step (2) is stannous octoate, and the initiator of use is phenylcarbinol.
According to method of the present invention, be characterised in that, the number-average molecular weight of the polyvinyl alcohol used in step (3) is 88000.
The present invention also provides the polylactic acid microsphere prepared by method of the present invention, is characterised in that, when poly(lactic acid) number-average molecular weight lower than 20000 time, described microballoon is hollow structure; When poly(lactic acid) number-average molecular weight higher than 50000 time, described microballoon is vesicular structure; When the number-average molecular weight of poly(lactic acid) is 20000-50000, described microballoon is many imitated vesicle structures.
the effect of invention
The present invention can carry out the pattern of Linear Control polylactic acid microsphere inside by the molecular weight controlling poly(lactic acid).The present invention can large-scale application to medicine carrying microballoons field, realize the scale operation of medicine carrying microballoons, reduce medicine carrying microballoons manufacture cost, also namely reduce the Financial cost that patient cures the disease.
Accompanying drawing explanation
Fig. 1 is the number-average molecular weight that represents poly(lactic acid) when being 5400, the sweep electron microscope photo of the internal structure of the polylactic acid microsphere of preparation.
Fig. 2 is the number-average molecular weight that represents poly(lactic acid) when being 13900, the sweep electron microscope photo of the internal structure of the polylactic acid microsphere of preparation.
Fig. 3 is the number-average molecular weight that represents poly(lactic acid) when being 24600, the sweep electron microscope photo of the internal structure of the polylactic acid microsphere of preparation.
Fig. 4 is the number-average molecular weight that represents poly(lactic acid) when being 48400, the sweep electron microscope photo of the internal structure of the polylactic acid microsphere of preparation.
Fig. 5 is the number-average molecular weight that represents poly(lactic acid) when being 141800, the sweep electron microscope photo of the internal structure of the polylactic acid microsphere of preparation.
Fig. 6 is the number-average molecular weight that represents poly(lactic acid) when being 278300, the sweep electron microscope photo of the internal structure of the polylactic acid microsphere of preparation.
In FIG, show the microballoon pattern after being smashed by magnetic agitation, microballoon inside has one and only has a larger hole, and be around the wall that poly(lactic acid) forms, the microballoon of this structure is hollow microsphere.
In fig. 2, the microballoon pattern after being smashed by magnetic agitation is shown.Microballoon inside has one and only has a larger hole, is around the wall that poly(lactic acid) forms, the microballoon hollow microsphere of this structure.
In figure 3, the microballoon pattern after freezing microtome section is shown.There is the hole that two diameters are larger microballoon inside, and all the other positions are fill in the inside of microballoon entity by many apertures, and the microballoon of this structure is a kind of many vesicas microballoon.
In the diagram, the microballoon pattern after freezing microtome section is shown.The inner overwhelming majority of whole microballoon is occupied by larger-diameter hole, and the quantity in hole is relatively less, and the microballoon of this kind of structure is many vesicas microballoon.
In Figure 5, the microballoon pattern after freezing microtome section is shown.The hole having a lot of aperture small-sized is filled in whole microballoon entity space inside, and do not have significantly large hole, also do not have the structure of wall, the microballoon of this kind of structure is porous microsphere.
In figure 6, the microballoon pattern after freezing microtome section is shown.The hole having a lot of aperture small-sized is filled in whole microballoon entity space inside, and do not have significantly large hole, also do not have the structure of wall, the microballoon of this kind of structure is porous microsphere.
Embodiment
In the present invention, the synthetic route of poly(lactic acid) is:
In the step (1) of the inventive method, i.e. in the synthesis of rac-Lactide, by controlling vacuum tightness and temperature of reaction, make D, Pfansteihl polycondensation obtains rac-Lactide crude product, then the method for rac-Lactide crude product preferably by heating up-lowering the temperature in ethyl acetate is dissolved-precipitation, obtains crystalline lactides.
The step that the described method by heating up-lowering the temperature is dissolved-precipitated comprises: join in the beaker containing ethyl acetate by the rac-Lactide crude product obtained, this beaker film seal, slowly be warming up to 60-90 DEG C under magnetic stirring, maintain the about 30-90 minute of this temperature, after rac-Lactide all dissolves, stop heating, slowly cool to room temperature, now solution is faint yellow.And then to be transferred to temperature be in the refrigerator of about-4 DEG C, approximately cooling there will be a large amount of white crystals precipitation after two hours, and supernatant liquid is faint yellow.This white crystals precipitation is the rac-Lactide after purification.Topple over and fall the faint yellow clear liquid in upper strata, obtain white crystal.Repeat aforesaid operations 5-6 time again, just can obtain the granular lactide particles of highly purified white crystals.
In the step (2) of the inventive method, i.e., in the synthesis of poly(lactic acid), the catalyzer of use is preferably stannous octoate, and the initiator of use is phenylcarbinol, also can use other catalyzer well known to those skilled in the art and initiator.The example of such as catalyzer has tin protochloride, zinc chloride, tin tetrachloride, aluminum chloride, the catalyzer such as iron trichloride, and the example of initiator has water, decyl alcohol, Virahol, the alcohols such as tetramethylolmethane.
In the step (2) of the inventive method, by the mass ratio of rac-Lactide and initiator is controlled at rac-Lactide: initiator is 1:(0.00005 ~ 0.05), be preferably 1:(0.0005 ~ 0.05), be more preferably 1:(0.0005 ~ 0.03), remain unchanged by making the amount of rac-Lactide, within the scope of aforementioned proportion, change the amount of initiator, polymerization obtains the poly(lactic acid) of different molecular weight.
In reality synthesis, such as taking rac-Lactide is 40g, and the catalyst quality added is generally about 0.3% of rac-Lactide, i.e. about 0.12g.According to the molecular weight of poly(lactic acid) to be synthesized, regulate the add-on of initiator (such as phenylcarbinol), as follows:
When molecular weight is 5000: 0.864g;
When molecular weight is 10000: 0.432g;
When molecular weight is 20000: 0.216g;
When molecular weight is 25000: 0.1728g;
When molecular weight is 30000: 0.144g;
When molecular weight is 50000: 0.0864g;
When molecular weight is 100000: 0.0432g;
When molecular weight is 200000: 0.0216g;
Need to illustrate: above molecular weight is the theoretical value average molecular weight expecting to obtain, but may can not get with theory on all four molecular weight in an experiment, and the molecular weight with theory is had certain difference by actual molecular weight, specifically can see embodiment.
In the step (3) of the inventive method, i.e. in the preparation of polylactic acid microsphere, the good solvent of use is the conventional methylene chloride in this area; The poor solvent used can be the most frequently used solvent in this area, as normal hexane, normal heptane, octane, octane-iso or n-dodecane etc.In the present invention, can use the arbitrary combination of any one or more in methylene dichloride and the above-mentioned poor solvent enumerated, preferably using by volume ratio is 9.5:0.5 ~ 8:2, is preferably the methylene dichloride of 9:1 and the organic solvent of normal hexane composition.
In the present invention, described molecular weight is number average molecular, and it is recorded by 400,000,000 nuclear magnetic resonance analyser hydrogen spectrums.
The measuring method of molecular weight is: the ratio of the spectrum peak area that the hydrogen atom on the spectrum peak area produced by the hydrogen atom calculated on the methyl on polylactic acid molecule chain and polylactic acid molecule end of the chain phenyl ring is produced, then is multiplied by 2.5 and is corrected acquisition.
Metering facility: 400,000,000 nuclear magnetic resonance analyser, model: ADVANCE2B/400MHZ, manufacturer: BRUKER company of Switzerland.
Below provide embodiments of the invention, its object only for explaining and illustrating, does not limit the present invention.
Embodiment 1(number-average molecular weight is the preparation of the polylactic acid microsphere of 5400)
(1) synthesis of rac-Lactide
By 1000ml D, Pfansteihl adds in the flask of 2L, under the agitation condition of 300-800 rev/min, by controlling vacuum tightness and temperature synthesis of lactide from crude product.The rate-determining steps of temperature and vacuum tightness is as follows:
Controlling vacuum tightness with water pump is-0.085MPa, and temperature heats up from 80 DEG C, and heating schedule is raise 3 DEG C per half an hour, is warmed up to 179 DEG C always.Keep 179 DEG C constant, change vacuum tightness, make vacuum tightness be reduced to-0.093MPa from-0.085MPa at leisure, this process, approximately need the time of 3 hours.Now no longer include water to produce.Then, change water pump into oil pump and vacuumize, temperature remains on 179 DEG C, and agitation condition is constant.Vacuumize and approximately carry out 2 hours.
Vacuumize 2 hours and add 15g zinc oxide in backward flask as catalyzer.Temperature slowly rises to 191 DEG C by 179 DEG C, and still vacuumize with oil pump, agitation condition is constant, and the drop having yellow-white is in this process distilled out.The yellow-white drop distilled is rac-Lactide crude product, collects in condensing works.Until do not have lactide droplets to produce, can stopped reaction.
The rac-Lactide crude product collected is dissolved-precipitation by the method heating up-lower the temperature in ethyl acetate, approximately carries out obtaining lily granular crystalline lactides for 5-6 time.The crystalline lactides obtained is put into moisture eliminator store for future use.
The concrete steps of being dissolved by the method heating up-lower the temperature-being precipitated comprise:
The pale yellow powder shape rac-Lactide crude product (about 171g) obtained is joined in the beaker containing 250ml ethyl acetate, this beaker film seal, slowly be warming up to 80 DEG C under magnetic stirring, maintain 80 DEG C about about 10 minutes, after rac-Lactide all dissolves, stop heating, slowly cool to room temperature, now solution is faint yellow.And then to be transferred to temperature be in the refrigerator of-4 DEG C, approximately cooling there will be a large amount of white crystals precipitation after two hours, and supernatant liquid is faint yellow.This white crystals precipitation is the rac-Lactide after purification.Topple over and fall the faint yellow clear liquid in upper strata, obtain white crystal.Repeat aforesaid operations 5-6 time again, just can obtain highly purified granular rac-Lactide white crystals.
(2) synthesis of poly(lactic acid)
Take the rac-Lactide obtained above of 40g, then the process by heating up-lowering the temperature in 150ml ethyl acetate dissolves-precipitation (namely purifying once according to above-mentioned steps), to remove impurity further, then dries 24 hours in vacuum drying oven.Afterwards the rac-Lactide of drying is loaded in the vacuum polymerization bottle of drying in advance.Then in polymerization bottle, 0.12g stannous octoate and 0.864g phenylcarbinol is added with minute hand head.Then by the heating lower sealing of polymerization bottle at alcohol blast burner.Then oil bath pan polymerization bottle being put into 140 DEG C heats, reaction 6-8 hour.Stannous octoate is catalyzer, and phenylcarbinol is initiator.The poly(lactic acid) high productivity computing instrument PL-GPC220 obtained is carried out molecular weight measurement, and recording its number-average molecular weight is 5400.
(3) preparation of polylactic acid microsphere
The poly(lactic acid) of above-mentioned for 500mg preparation is dissolved in the mixed solvent of 9ml methylene dichloride and 1ml normal hexane, then above-mentioned solution is added drop-wise in the 100ml aqueous solution containing 1g polyvinyl alcohol (PVA, number-average molecular weight is 88000) by syringe.Under magnetic stirring, organic solvent constantly volatilizees, and the organic phase oil droplet in the aqueous solution is hardening gradually, and then solidify to form microballoon.The cut-away view of this polylactic acid microsphere is with reference to Fig. 1.The particle diameter of the microballoon obtained is between 100-250 micron, and productive rate is 62%.
Embodiment 2(number-average molecular weight is the preparation of the polylactic acid microsphere of 13900)
Repeat the step of embodiment 1, except in the synthesis of step (2) poly(lactic acid), change into outside 0.432g by the consumption of phenylcarbinol, all the other are constant.The poly(lactic acid) obtained is carried out molecular weight measurement, and its number-average molecular weight is 13900.The cut-away view of this polylactic acid microsphere is with reference to Fig. 2.The particle diameter of the microballoon obtained is between 50-100 micron, and productive rate is 71%.
Embodiment 3(number-average molecular weight is the preparation of the polylactic acid microsphere of 24600)
Repeat the step of embodiment 1, except in the synthesis of step (2) poly(lactic acid), change into outside 0.1728g by the consumption of phenylcarbinol, all the other are constant.The poly(lactic acid) obtained is carried out molecular weight measurement, and its number-average molecular weight is 24600.The cut-away view of this polylactic acid microsphere is with reference to Fig. 3.The microspherulite diameter obtained is between 100-150 micron, and productive rate is 74%.
Embodiment 4(number-average molecular weight is the preparation of the polylactic acid microsphere of 29800)
Repeat the step of embodiment 1, except in the synthesis of step (2) poly(lactic acid), change into outside 0.144g by the consumption of phenylcarbinol, all the other are constant.The poly(lactic acid) obtained is carried out molecular weight measurement, and its number-average molecular weight is 29800.
Embodiment 5(number-average molecular weight is the preparation of the polylactic acid microsphere of 48400)
Repeat the step of embodiment 1, except in the synthesis of step (2) poly(lactic acid), change into outside 0.09g by the consumption of phenylcarbinol, all the other are constant.The poly(lactic acid) obtained is carried out molecular weight measurement, and its number-average molecular weight is 48400.The cut-away view of this polylactic acid microsphere is with reference to Fig. 4.The microspherulite diameter obtained is between 50-70 micron, and productive rate is 66%.
Embodiment 6(number-average molecular weight is the preparation of the polylactic acid microsphere of 98100)
Repeat the step of embodiment 1, except in the synthesis of step (2) poly(lactic acid), change into outside 0.054g by the consumption of phenylcarbinol, all the other are constant.The poly(lactic acid) obtained is carried out molecular weight measurement, and its number-average molecular weight is 98100.
Embodiment 7(number-average molecular weight is the preparation of the polylactic acid microsphere of 141800)
Repeat the step of embodiment 1, except in the synthesis of step (2) poly(lactic acid), change into outside 0.0432g by the consumption of phenylcarbinol, all the other are constant.The poly(lactic acid) obtained is carried out molecular weight measurement, and its number-average molecular weight is 141800.The cut-away view of this polylactic acid microsphere is with reference to Fig. 5.The microspherulite diameter obtained is between 50-100 micron, and productive rate is 64%.
Embodiment 8(number-average molecular weight is the preparation of the polylactic acid microsphere of 278300)
Repeat the step of embodiment 1, except in the synthesis of step (2) poly(lactic acid), change into outside 0.0216g by the consumption of phenylcarbinol, all the other are constant.The poly(lactic acid) obtained is carried out molecular weight measurement, and its number-average molecular weight is 278300.The cut-away view of this polylactic acid microsphere is with reference to Fig. 6.The particle diameter of the microballoon obtained is between 50-70 micron, and productive rate is 77%.
According to above embodiment, when poly(lactic acid) number-average molecular weight lower than 20000 time, obtain the microballoon of hollow structure; When poly(lactic acid) number-average molecular weight higher than 50000 time, obtain the microballoon of vesicular structure; When the number-average molecular weight of poly(lactic acid) is 20000-50000, obtain the microballoon of many imitated vesicle structures.Thus, the molecular weight that present invention achieves by controlling poly(lactic acid) carrys out the pattern of Linear Control polylactic acid microsphere inside.
Claims (6)
1. regulate and control a method for polylactic acid microsphere internal morphology, comprise the following steps:
(1) synthesis of rac-Lactide
With D, Pfansteihl is raw material, under the temperature of reaction of-0.095MPa to the vacuum tightness of-0.085MPa and 170 DEG C to 195 DEG C, carries out polycondensation in the presence of a catalyst, obtains rac-Lactide crude product; Dissolved by rac-Lactide crude product, precipitation, obtains crystalline lactides, for subsequent use;
(2) synthesis of poly(lactic acid)
With the crystalline lactides of gained for raw material, under the existence of catalyzer and initiator, carry out polymerization and obtain poly(lactic acid),
By the mass ratio of rac-Lactide and initiator is controlled at rac-Lactide in step (2): initiator is 1:(0.00054 ~ 0.0108), remain unchanged by making the amount of rac-Lactide, within the scope of aforementioned proportion, change the amount of initiator, polymerization obtains the poly(lactic acid) of different molecular weight;
(3) preparation of polylactic acid microsphere
Poly(lactic acid) being dissolved in by volume ratio is obtain PLA solution in the organic solvent that forms of the methylene dichloride of 9.5:0.5 ~ 8:2 and normal hexane, is then added drop-wise in polyvinyl alcohol water solution by PLA solution, solidify to form polylactic acid microsphere under magnetic stirring;
Be characterised in that: when poly(lactic acid) number-average molecular weight lower than 20000 time, obtain the microballoon of hollow structure; When poly(lactic acid) number-average molecular weight higher than 50000 time, obtain the microballoon of vesicular structure; When the number-average molecular weight of poly(lactic acid) is 20000-50000, obtain the microballoon of many imitated vesicle structures.
2. method according to claim 1, is characterised in that, the catalyzer used in step (1) is zinc oxide.
3. method according to claim 1 and 2, is characterised in that, in step (1), rac-Lactide crude product is dissolved-precipitation by the method heating up-lower the temperature in ethyl acetate, obtains crystalline lactides.
4. method according to claim 1 and 2, is characterised in that, the catalyzer used in step (2) is stannous octoate, and the initiator of use is phenylcarbinol.
5. method according to claim 1 and 2, is characterised in that, the number-average molecular weight of the polyvinyl alcohol used in step (3) is 88000.
6. polylactic acid microsphere prepared by the method described in any one of claim 1-5, is characterised in that, when poly(lactic acid) number-average molecular weight lower than 20000 time, described microballoon is hollow structure; When poly(lactic acid) number-average molecular weight higher than 50000 time, described microballoon is vesicular structure; When the number-average molecular weight of poly(lactic acid) is 20000-50000, described microballoon is many imitated vesicle structures.
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| JP7014528B2 (en) * | 2017-05-19 | 2022-02-01 | 株式会社日本触媒 | Biodegradable resin particles |
| CN107698969A (en) * | 2017-09-12 | 2018-02-16 | 滁州远方车船装备工程有限公司 | A kind of track traffic retardant-rubber tenacity increased nylon bellows material and preparation method thereof |
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| CN113736106A (en) * | 2020-05-16 | 2021-12-03 | 中国科学院理化技术研究所 | Hollow polyester microsphere, preparation method and application thereof |
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