CN108047464A - A kind of degradable polymer microspheres and preparation method thereof - Google Patents
A kind of degradable polymer microspheres and preparation method thereof Download PDFInfo
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- CN108047464A CN108047464A CN201711363366.5A CN201711363366A CN108047464A CN 108047464 A CN108047464 A CN 108047464A CN 201711363366 A CN201711363366 A CN 201711363366A CN 108047464 A CN108047464 A CN 108047464A
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- 239000004005 microsphere Substances 0.000 title claims abstract description 31
- 229920006237 degradable polymer Polymers 0.000 title claims abstract description 28
- 238000002360 preparation method Methods 0.000 title claims abstract description 27
- 229920000642 polymer Polymers 0.000 claims abstract description 56
- 238000000034 method Methods 0.000 claims abstract description 49
- 239000003960 organic solvent Substances 0.000 claims abstract description 15
- 239000000243 solution Substances 0.000 claims description 15
- 239000007864 aqueous solution Substances 0.000 claims description 14
- 238000002156 mixing Methods 0.000 claims description 12
- 239000003995 emulsifying agent Substances 0.000 claims description 10
- 210000005239 tubule Anatomy 0.000 claims description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 8
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 8
- 239000006185 dispersion Substances 0.000 claims description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 6
- 239000000203 mixture Substances 0.000 claims description 6
- 239000000725 suspension Substances 0.000 claims description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 5
- 238000013019 agitation Methods 0.000 claims description 5
- 238000003756 stirring Methods 0.000 claims description 5
- 229920001577 copolymer Polymers 0.000 claims description 4
- 229920000747 poly(lactic acid) Polymers 0.000 claims description 4
- 239000004626 polylactic acid Substances 0.000 claims description 4
- 239000006228 supernatant Substances 0.000 claims description 4
- 229920001244 Poly(D,L-lactide) Polymers 0.000 claims description 3
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 claims description 3
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 claims description 3
- 238000001914 filtration Methods 0.000 claims description 3
- 229920001610 polycaprolactone Polymers 0.000 claims description 3
- 239000004632 polycaprolactone Substances 0.000 claims description 3
- -1 polytrimethylene carbonic acid Polymers 0.000 claims description 3
- 239000000126 substance Substances 0.000 claims description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 3
- 238000007334 copolymerization reaction Methods 0.000 claims description 2
- 210000000481 breast Anatomy 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 14
- 239000012074 organic phase Substances 0.000 abstract description 13
- 239000012071 phase Substances 0.000 abstract description 13
- 238000007711 solidification Methods 0.000 abstract description 10
- 238000009826 distribution Methods 0.000 abstract description 8
- 238000004945 emulsification Methods 0.000 abstract description 5
- 230000008023 solidification Effects 0.000 abstract description 4
- 239000000470 constituent Substances 0.000 description 11
- 238000005516 engineering process Methods 0.000 description 7
- JVTAAEKCZFNVCJ-REOHCLBHSA-N L-lactic acid Chemical compound C[C@H](O)C(O)=O JVTAAEKCZFNVCJ-REOHCLBHSA-N 0.000 description 6
- 230000008569 process Effects 0.000 description 6
- 230000003321 amplification Effects 0.000 description 5
- 238000003199 nucleic acid amplification method Methods 0.000 description 5
- 230000000694 effects Effects 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 230000001804 emulsifying effect Effects 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 230000003287 optical effect Effects 0.000 description 3
- 230000002572 peristaltic effect Effects 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 230000003796 beauty Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical class ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- JJTUDXZGHPGLLC-UHFFFAOYSA-N lactide Chemical compound CC1OC(=O)C(C)OC1=O JJTUDXZGHPGLLC-UHFFFAOYSA-N 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J3/00—Processes of treating or compounding macromolecular substances
- C08J3/12—Powdering or granulating
- C08J3/16—Powdering or granulating by coagulating dispersions
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J2367/00—Characterised by the use of polyesters obtained by reactions forming a carboxylic ester link in the main chain; Derivatives of such polymers
- C08J2367/04—Polyesters derived from hydroxy carboxylic acids, e.g. lactones
Abstract
The present invention provides a kind of degradable polymer microspheres and preparation method thereof.The present invention combines the characteristics of miniflow method, limits the size of organic phase in advance using a thin pipeline in solidification method is emulsified so that organic phase is become the microballoon of preliminary dimension when being slowly injected into a large amount of water phases by THE ADIABATIC SHEAR IN.Organic solvent in micron level polymer microballoon can be quickly diffused in water phase, prevent being adhered between later stage polymer microballoon.Method provided by the invention improves the Microsphere Size uniformity of conventional emulsification solidification method, improves the quality and yield of polymer microballoon.This kind of simple and quick preparation method for preparing the preferable degradable polymer microspheres of homogeneity, by allocating the various technical parameters in microballoon preparation process, the microspherulite diameter distribution prepared is homogeneous, diameter breadth coefficient has significance below 25%, compared to microspherulite diameter distribution prepared by conventional multi-emulsion method.
Description
Technical field
The present invention relates to the preparation field of degradable microsphere, in particular to a kind of degradable polymer microspheres and its
Preparation method.
Background technology
Degradable polymer using polylactic acid as representative because its can it is degradable in human body be small point nontoxic to human body
Son and be widely used in medical treatment, medicine and beauty industry.Particularly, polymer microballoon, micro-capsule are due to it is with high added value
By further investigation and use.At present using polymer as raw material prepare the method for microballoon mainly have emulsification solidification method, spray drying process,
The precipitation method, the liquid level method of development and film emulsifying technology.Solidification method is wherein emulsified because its equipment is simple, simple operation, easily amplification life
It produces and is widely adopted.Following technical literature discloses several methods using emulsification-solidification method production microballoon.
Patent document 1：Chinese patent, publication number:1586704；
Patent document 2：Chinese patent, publication number:104448356；
Patent document 3：Chinese patent, publication number:102389756；
Patent document 4：Chinese patent, publication number:105943506；
However the method influence factor is numerous, obtained polymer microballoon Size Distribution is wider.In production specified particle diameter model
Overall productivity is relatively low when enclosing interior micrograde polymer microsphere.
The preferable method of preparation homogeneity for being seen in document at present mainly has film emulsifying technology, polymerisation method, acoustically-driven
Method and miniflow method etc..Wherein film emulsifying technology needs special micropore glass film, and equipment is expensive and compares and is difficult to prepare 20um
Above large scale microballoon.Acoustically-driven method is still under test, and technology is still immature.Polymerisation method be not suitable for prepare with
Polylactic acid is the micro-sphere material of representative.And miniflow method controls microballoon size by microchannel size Come, it is different size of producing
It needs to redesign micro-fluidic chip during microballoon, adaptability is narrow.The method exists simultaneously low output, the problems such as easily blocking.
Therefore a kind of easy method that disclosure satisfy that mass production polymer microballoon is still needed to.Emulsification-solidification method at present
Majority work is concentrated mainly on type selecting, the design of mulser of emulsifier etc. work, but to the mixing of organic phase and water phase
Method is related to seldom.Most methods generate polymer microballoon using the method stirred after being added dropwise or mixing.These methods are to micro-
The size degree of controllability of ball is poor, and easily leads to the problem of polymer microballoon and be adhered, even lump.
The content of the invention
In view of this, the defects of the technical problem to be solved in the present invention is to overcome the prior art, providing one kind can drop
Depolymerize object microballoon and preparation method thereof.
The preparation method of this kind of degradable polymer microspheres, comprises the following steps：
S1：Polymer is dissolved in volatile organic solvent and obtains polymer solution；
S2：Under agitation, the polymer solution obtained in the S1 is injected using flow pump by tubule
Into emulsifier aqueous solution；
S3：After the completion of mixing, continue to stir, remove organic solvent and obtain suspension；
S4：Gained suspension in the S3 is stood, polymer microballoon is made fully to settle, abandoning supernatant；
S5：Polymer microballoon is collected by filtration, washs, be dried to obtain degradable polymer microspheres.
In some embodiments, in the S2, under agitation, the polymer solution that will be obtained in the S1
It is injected into using flow pump by tubule in emulsifier aqueous solution.
In some embodiments, the polymer in the S1 is handed over including l-lactic acid, poly-dl-lactide, poly- second third
Any one in ester, polycaprolactone, polytrimethylene carbonic acid and polylactide-caprolactone copolymer or arbitrary several copolymerization
Object or blend.
In some embodiments, organic solvent volatile in the S1 be dichloromethane, chloroform, acetic acid second
Ester, methyl acetate, acetone, any one in tetrahydrofuran or arbitrary several mixture.
In some embodiments, mass concentration of the polymer in the polymer solution described in the S1 is 1%
~10%.
In some embodiments, the flow pump in the S2 is peristaltic pump or diaphragm pump；
The tubule is resist chemical pipeline；
The tubule interior diameter is in 0.6mm~2.16mm；
The flow velocity that the polymer solution is added in the emulsifier aqueous solution is 1~10mL/min.
In some embodiments, mixing plant used is dispersion machine in the S2；The dispersion impeller diameter of the dispersion machine
For 40mm~100mm.
In some embodiments, the concentration of emulsifier aqueous solution described in the S2 is 0.05~0.5%；In the S2
The ratio between the organic solvent and aqueous solution are 1:5~1:20.
In some embodiments, mixing speed is 240~360rpm in the S3, and temperature is 25~35 DEG C.
In some embodiments, in the S4 time of repose for 0.5 it is small when~8 it is small when.
The average diameter of this kind of polymer microballoon is between 10um~100um, and diameter breadth coefficient is below 25%.
The present invention combines the characteristics of miniflow method, and organic phase is limited in advance using a thin pipeline in emulsification-solidification method
Size so that organic phase when being slowly injected into a large amount of water phases by THE ADIABATIC SHEAR IN become preliminary dimension microballoon.It is micro-
Organic solvent in the other polymer microballoon of meter level can be quickly diffused in water phase, prevent being adhered between later stage polymer microballoon.
Method provided by the invention improves the Microsphere Size uniformity of conventional emulsification-solidification method, improves the quality of polymer microballoon
With yield.
It is understood that a kind of present invention determine that simple and quick preparation homogeneity preferable degradable polymer microspheres
Preparation method, by allocating the various technical parameters in microballoon preparation process, the microspherulite diameter prepared is distributed homogeneous, diameter
Breadth coefficient has significance below 25%, compared to microspherulite diameter distribution prepared by conventional multi-emulsion method.
In short, this kind of degradable polymer microspheres structural stability is good, preparation method is easily operated.It can quickly, conveniently
Ground prepares degradable polymer microspheres.Greatly improve the convenience of operation.More meet demand in actual application.
In conclusion a kind of degradable polymer microspheres provided by the invention preparation method and prepare it is degradable
Polymer microballoon has the advantages that above-mentioned many and value, and there are no similar method in similar product and publish or make
With and really belong to innovation, generate handy and practical effect, more existing technology have effects that promote it is multinomial, so as to more suitable
In practicality, and with extensive industrial value.
Description of the drawings
It should be appreciated that the following drawings illustrates only certain embodiments of the present invention, therefore it is not construed as to model
The restriction enclosed, for those of ordinary skill in the art, without creative efforts, can also be according to these
Attached drawing obtains other relevant attached drawings.
Fig. 1 be the embodiment of the present invention 1 in degradable polymer microspheres distribution map and optical microscope photograph (illustration,
50 times of amplification factors)
Fig. 2 is that the distribution map of degradable polymer microspheres and optical microscope photograph (are inserted in the embodiment of the present invention 2
Figure, 50 times of amplification factors)
Fig. 3 is that the distribution map of degradable polymer microspheres and optical microscope photograph (are inserted in the embodiment of the present invention 3
Figure, 50 times of amplification factors)
Fig. 4 is the scanning electron microscope (SEM) photograph of degradable polymer microspheres in the embodiment of the present invention 1.
Specific embodiment
Hereinafter, the various embodiments of the disclosure will be described more fully with reference to attached drawing.The disclosure can have various realities
Example is applied, and can adjust and change wherein.Therefore, will in more detail be retouched with reference to the specific embodiment being shown in the drawings
State the disclosure.It should be understood, however, that：There is no the meanings that the various embodiments of the disclosure are limited to specific embodiment disclosed herein
Figure, but the disclosure should be interpreted as covering all adjustment in the spirit and scope for the various embodiments for falling into the disclosure, etc.
Jljl and/or alternative.Description taken together with the accompanying drawings, the same same element of reference numerals.
Hereinafter, disclosed in the term " comprising " that can be used in the various embodiments of the disclosure or " may include " instruction
Function, operation or the presence of element, and do not limit the increase of one or more functions, operation or element.
In the various embodiments of the disclosure, stating "or" or " at least one in A or/and B " includes what is listed file names with
Any combinations of word or all combinations.For example, statement " A or B " or " at least one in A or/and B " may include A, may include
B may include A and B both.
The statement (" first ", " second " etc.) used in the various embodiments of the disclosure can be modified in various implementations
Various constituent element in example, but respective sets can not be limited into element.For example, presented above be not intended to limit the suitable of the element
Sequence and/or importance.The purpose presented above for being only used for differentiating an element and other elements.For example, the first user fills
It puts and indicates different user device with second user device, although the two is all user apparatus.For example, each of the disclosure is not being departed from
In the case of the scope of kind embodiment, first element is referred to alternatively as second element, and similarly, second element is also referred to as first
Element.
It should be noted that：It, can be by the first composition member if a constituent element ' attach ' to another constituent element by description
Part is directly connected to the second constituent element, and " connection " the 3rd can be formed between the first constituent element and the second constituent element
Element.On the contrary, when a constituent element " being directly connected to " is arrived another constituent element, it will be appreciated that be in the first constituent element
And second the 3rd constituent element is not present between constituent element.
The term used in the various embodiments of the disclosure is used only for the purpose of describing specific embodiments and not anticipates
In the various embodiments of the limitation disclosure.As used herein, singulative is intended to also include plural form, unless context is clear
Chu it is indicated otherwise.Unless otherwise defined, otherwise all terms (including technical term and scientific terminology) used herein have
There is the meaning identical with the various normally understood meanings of embodiment one skilled in the art of the disclosure.The term
(term such as limited in the dictionary generally used) is to be interpreted as having and situational meaning in the related technical field
Identical meaning and the meaning of Utopian meaning or overly formal will be interpreted as having, unless in the various of the disclosure
It is clearly defined in embodiment.
Referring to Fig. 1 to Fig. 3, in some embodiments of the invention, a kind of preparation method of degradable polymer microspheres, including
Following steps：
S1：Polymer is dissolved in volatile organic solvent and obtains polymer solution；
S2：Under agitation, the polymer solution obtained in the S1 is injected using flow pump by tubule
Into emulsifier aqueous solution；
S3：After the completion of mixing, continue to stir, remove organic solvent and obtain suspension；
S4：Gained suspension in the S3 is stood, polymer microballoon is made fully to settle, abandoning supernatant；
S5：Polymer microballoon is collected by filtration, washs, be dried to obtain degradable polymer microspheres.
Above-mentioned, with reference to the characteristics of miniflow method, using a thin pipeline, limitation has the present invention in advance in emulsification-solidification method
The size of machine phase so that organic phase becomes the micro- of preliminary dimension when being slowly injected into a large amount of water phases by THE ADIABATIC SHEAR IN
Ball.Organic solvent in micron level polymer microballoon can be quickly diffused in water phase, prevented between later stage polymer microballoon
It is adhered.Method provided by the invention improves the Microsphere Size uniformity of conventional emulsification-solidification method, improves polymer microballoon
Quality and yield.
It is understood that a kind of present invention determine that simple and quick preparation homogeneity preferable degradable polymer microspheres
Preparation method, by allocating the various technical parameters in microballoon preparation process, the microspherulite diameter prepared is distributed homogeneous, diameter
Breadth coefficient has significance below 25%, compared to microspherulite diameter distribution prepared by conventional multi-emulsion method.
In short, this kind of degradable polymer microspheres structural stability is good, preparation method is easily operated.It can quickly, conveniently
Ground prepares degradable polymer microspheres.Greatly improve the convenience of operation.More meet demand in actual application.
In conclusion a kind of degradable polymer microspheres provided by the invention preparation method and prepare it is degradable
Polymer microballoon has the advantages that above-mentioned many and value, and there are no similar method in similar product and publish or make
With and really belong to innovation, generate handy and practical effect, more existing technology have effects that promote it is multinomial, so as to more suitable
In practicality, and with extensive industrial value.
In some embodiments of the invention, the polymer in the S1 includes l-lactic acid, poly-dl-lactide, poly- second
In lactide, polycaprolactone, polytrimethylene carbonic acid and polylactide-caprolactone copolymer any one or it is arbitrary several
Copolymer or blend.
In some embodiments of the invention, organic solvent volatile in the S1 be dichloromethane, chloroform, acetic acid
Ethyl ester, methyl acetate, acetone, any one in tetrahydrofuran or arbitrary several mixture.
In some embodiments of the invention, mass concentration of the polymer in the polymer solution described in the S1 is
1%~10%.
In some embodiments of the invention, the flow pump in the S2 is peristaltic pump or diaphragm pump；
The tubule is resist chemical pipeline；
The tubule interior diameter is in 0.6mm~2.16mm；
The flow velocity that the polymer solution is added in the emulsifier aqueous solution is 1~10mL/min.
In some embodiments of the invention, the concentration of emulsifier aqueous solution described in the S2 is 0.05~0.5%；It is described
The ratio between organic solvent described in S2 and aqueous solution are 1:5~1:20.
In some embodiments of the invention, mixing plant used is dispersion machine in the S2；The dispersion impeller of the dispersion machine
A diameter of 40mm~100mm.
In some embodiments of the invention, mixing speed is 240~360rpm in the S3, and temperature is 25~35 DEG C.
In some embodiments of the invention, in the S4 time of repose for 0.5 it is small when~8 it is small when.
Between 10um~100um, diameter breadth coefficient exists a kind of polymer microballoon average diameter provided by the invention
Less than 25%.
It should be appreciated that although this specification is described in terms of embodiments, but not each embodiment only includes one
A independent technical solution, this description of the specification is merely for the sake of clarity, and those skilled in the art should will say
For bright book as an entirety, the technical solution in each embodiment may also be suitably combined to form those skilled in the art can
With the other embodiment of understanding.
Embodiment 1
The accurate 15g l-lactic acid (inherent viscosity 1.18dL/g, solvent chloroform) that weighs is dissolved in 250mL analyses pure two
In chloromethanes, as organic phase；2500mL PVA-210 aqueous solutions are prepared simultaneously, as water phase；Under agitation
It is water-soluble to be slowly injected into PVA by (600rpm) by 12G syringe needles using peristaltic pump with the injection rate of 4mL/min for above-mentioned organic phase
Under liquid liquid level.After completion to be injected, then with the rotating speed of 360rpm stirring 12 it is small when to remove solvent.Then when standing 1 is small, abandon
Supernatant is removed, precipitation is filtered, is cleaned 3 times with deionized water, is freeze-dried up to polylactic acid microsphere.
Embodiment 2 (instillation control group)
The preparation method of organic phase and water phase is same as Example 1；Except for the following differences, other are for the preparation method of microballoon
It is same as Example 1：
During the addition process, syringe needle is located at water phase ullage to above-mentioned organic phase, and organic phase adds in water in droplets
Xiang Zhong.
Embodiment 3 (mixing control group)
The preparation method of organic phase and water phase is same as Example 1；Except for the following differences, other are for the preparation method of microballoon
It is same as Example 1：
Above-mentioned organic phase is directly poured into water phase, then starts to stir same time.
Test case 1
The form of polymer microballoon is shot by light microscope with grain size and measured.It is random under 50 times of amplification factors
Each sample is shot, should contain total at least 500 polymer microballoons in gained photo.Grain size point is utilized to the photo of gained
Analysis measures the size of all microballoons, and calculates its average-size (Dave), mean mass size (D4,3) and size be located at 40-63
Volume fraction (the w shared by microballoon between micron[40-63]).It is as follows to calculate publicity：
(diameter breadth coefficient)
| Dave/μm | D4,3/μm | w[40-63]/ % | CV | |
| Embodiment 1 | 49.42 | 56.22 | 74.43 | 0.22 |
| Embodiment 2 | 34.59 | 72.58 | 20.00 | 0.63 |
| Embodiment 3 | 40.77 | 55.56 | 58.57 | 0.39 |
Inventor states that the present invention can only for of the invention by a series of be described in detail of those listed above
Row embodiment illustrates, but the invention is not limited in above-mentioned detailed process equipment and technological processes.And i.e. not
Mean that the present invention should rely on above-mentioned detailed process equipment and technological process and could implement.Person of ordinary skill in the field should
This is clear, any improvement in the present invention, and the equivalence replacement and auxiliary element to each raw material of product of the present invention add, are specific square
Selection of formula etc. is all fallen within protection scope of the present invention and the open scope.
Claims (10)
1. a kind of preparation method of degradable polymer microspheres, it is characterised in that：Comprise the following steps：
S1：Polymer is dissolved in volatile organic solvent and obtains polymer solution；
S2：Under agitation, the polymer solution obtained in the S1 is injected into breast using flow pump by tubule
In agent aqueous solution；
S3：After the completion of mixing, continue to stir, remove organic solvent and obtain suspension；
S4：Gained suspension in the S3 is stood, polymer microballoon is made fully to settle, abandoning supernatant；
S5：Polymer microballoon is collected by filtration, washs, be dried to obtain degradable polymer microspheres.
2. a kind of degradable polymer microspheres as described in claim 1, it is characterised in that：Polymer in the S1 includes a left side
Revolve polylactic acid, poly-dl-lactide, poly (glycolide-lactide), polycaprolactone, polytrimethylene carbonic acid and polylactide-caprolactone copolymerization
Any one in object or arbitrary several copolymer or blend.
3. method for preparing polymer micro as described in claim 1, it is characterised in that：Volatile organic solvent in the S1
For dichloromethane, chloroform, ethyl acetate, methyl acetate, acetone, in tetrahydrofuran any one or it is arbitrary several mixed
Close object.
4. method for preparing polymer micro as described in claim 1, it is characterised in that：Polymer is in described described in the S1
Mass concentration in polymer solution is 1%~10%.
5. method for preparing polymer micro as described in claim 1, it is characterised in that：The flow pump in the S2 is compacted
Dynamic pump or diaphragm pump；
The tubule is resist chemical pipeline；
The tubule interior diameter is in 0.6mm~2.16mm；
The flow velocity that the polymer solution is added in the emulsifier aqueous solution is 1~10mL/min.
6. method for preparing polymer micro as described in claim 1, it is characterised in that：Emulsifier aqueous solution described in the S2
Concentration be 0.05~0.5%；The ratio between organic solvent and aqueous solution described in the S2 are 1:5~1:20.
7. method for preparing polymer micro as described in claim 1, it is characterised in that：Mixing plant used is point in the S2
Dissipate machine；A diameter of 40mm~the 100mm of dispersion impeller of the dispersion machine.
8. method for preparing polymer micro as described in claim 1, it is characterised in that：In the S3 mixing speed for 240~
360rpm, temperature are 25~35 DEG C.
9. method for preparing polymer micro as described in claim 1, it is characterised in that：Time of repose is small for 0.5 in the S4
When~8 it is small when.
10. a kind of polymer microballoon, it is characterised in that：It is made as the preparation method described in claim 1~9, it is described degradable
Polymer microballoon average diameter is between 10um~100um, and diameter breadth coefficient is below 25%.
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| CN201711363366.5A CN108047464A (en) | 2017-12-18 | 2017-12-18 | A kind of degradable polymer microspheres and preparation method thereof |
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| CN201711363366.5A CN108047464A (en) | 2017-12-18 | 2017-12-18 | A kind of degradable polymer microspheres and preparation method thereof |
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| CN108047464A true CN108047464A (en) | 2018-05-18 |
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Cited By (5)
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| CN109010910A (en) * | 2018-08-24 | 2018-12-18 | 普丽妍（南京）医疗科技有限公司 | A kind of preparation method of injectable l-lactic acid microballoon |
| 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 |
| CN110938328A (en) * | 2019-10-23 | 2020-03-31 | 清远高新华园科技协同创新研究院有限公司 | Functional polymer microsphere for automobile coating, preparation method and production equipment |
| CN113546060A (en) * | 2020-04-08 | 2021-10-26 | 江苏长泰药业有限公司 | Naltrexone microspheres |
| CN114805863A (en) * | 2022-05-30 | 2022-07-29 | 伊正(苏州)生物科技有限公司 | Polymer microsphere and preparation method thereof |
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Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN109010910A (en) * | 2018-08-24 | 2018-12-18 | 普丽妍（南京）医疗科技有限公司 | A kind of preparation method of injectable l-lactic acid microballoon |
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| 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 |
| CN110681323B (en) * | 2019-08-26 | 2021-12-21 | 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 |
| CN110938328A (en) * | 2019-10-23 | 2020-03-31 | 清远高新华园科技协同创新研究院有限公司 | Functional polymer microsphere for automobile coating, preparation method and production equipment |
| CN113546060A (en) * | 2020-04-08 | 2021-10-26 | 江苏长泰药业有限公司 | Naltrexone microspheres |
| CN113546060B (en) * | 2020-04-08 | 2023-04-07 | 江苏长泰药业有限公司 | Naltrexone microspheres |
| CN114805863A (en) * | 2022-05-30 | 2022-07-29 | 伊正(苏州)生物科技有限公司 | Polymer microsphere and preparation method thereof |
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