CN106860428A - Polymer overmold Nano medication preparation facilities and preparation method - Google Patents
Polymer overmold Nano medication preparation facilities and preparation method Download PDFInfo
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- CN106860428A CN106860428A CN201710095161.7A CN201710095161A CN106860428A CN 106860428 A CN106860428 A CN 106860428A CN 201710095161 A CN201710095161 A CN 201710095161A CN 106860428 A CN106860428 A CN 106860428A
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- 239000003814 drug Substances 0.000 title claims abstract description 88
- 229920000642 polymer Polymers 0.000 title claims abstract description 68
- 229940079593 drug Drugs 0.000 title claims abstract description 57
- 238000002360 preparation method Methods 0.000 title claims abstract description 47
- 239000000835 fiber Substances 0.000 claims abstract description 102
- 230000002572 peristaltic effect Effects 0.000 claims abstract description 37
- 239000002904 solvent Substances 0.000 claims abstract description 27
- 238000001914 filtration Methods 0.000 claims abstract description 19
- 239000000047 product Substances 0.000 claims abstract description 6
- 239000012467 final product Substances 0.000 claims abstract description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 28
- 239000013078 crystal Substances 0.000 claims description 12
- 238000000034 method Methods 0.000 claims description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 8
- IIUZTXTZRGLYTI-UHFFFAOYSA-N Dihydrogriseofulvin Natural products COC1CC(=O)CC(C)C11C(=O)C(C(OC)=CC(OC)=C2Cl)=C2O1 IIUZTXTZRGLYTI-UHFFFAOYSA-N 0.000 claims description 7
- UXWOXTQWVMFRSE-UHFFFAOYSA-N Griseoviridin Natural products O=C1OC(C)CC=C(C(NCC=CC=CC(O)CC(O)C2)=O)SCC1NC(=O)C1=COC2=N1 UXWOXTQWVMFRSE-UHFFFAOYSA-N 0.000 claims description 7
- DDUHZTYCFQRHIY-UHFFFAOYSA-N Negwer: 6874 Natural products COC1=CC(=O)CC(C)C11C(=O)C(C(OC)=CC(OC)=C2Cl)=C2O1 DDUHZTYCFQRHIY-UHFFFAOYSA-N 0.000 claims description 7
- 239000002033 PVDF binder Substances 0.000 claims description 7
- 239000008367 deionised water Substances 0.000 claims description 7
- 229910021641 deionized water Inorganic materials 0.000 claims description 7
- DDUHZTYCFQRHIY-RBHXEPJQSA-N griseofulvin Chemical compound COC1=CC(=O)C[C@@H](C)[C@@]11C(=O)C(C(OC)=CC(OC)=C2Cl)=C2O1 DDUHZTYCFQRHIY-RBHXEPJQSA-N 0.000 claims description 7
- 229960002867 griseofulvin Drugs 0.000 claims description 7
- 229920002981 polyvinylidene fluoride Polymers 0.000 claims description 7
- 238000002604 ultrasonography Methods 0.000 claims description 7
- 239000012528 membrane Substances 0.000 claims description 6
- 238000001728 nano-filtration Methods 0.000 claims description 6
- 239000012530 fluid Substances 0.000 claims description 5
- 238000010899 nucleation Methods 0.000 claims description 5
- 230000006911 nucleation Effects 0.000 claims description 5
- 239000004925 Acrylic resin Substances 0.000 claims description 3
- 229920000178 Acrylic resin Polymers 0.000 claims description 3
- 239000012065 filter cake Substances 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 239000002245 particle Substances 0.000 description 11
- 238000005516 engineering process Methods 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 6
- 239000011248 coating agent Substances 0.000 description 5
- 238000000576 coating method Methods 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 4
- 239000002114 nanocomposite Substances 0.000 description 4
- 239000002105 nanoparticle Substances 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 238000005253 cladding Methods 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 238000001046 rapid expansion of supercritical solution Methods 0.000 description 3
- 229920003134 Eudragit® polymer Polymers 0.000 description 2
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 2
- 238000010923 batch production Methods 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- VFLDPWHFBUODDF-FCXRPNKRSA-N curcumin Chemical compound C1=C(O)C(OC)=CC(\C=C\C(=O)CC(=O)\C=C\C=2C=C(OC)C(O)=CC=2)=C1 VFLDPWHFBUODDF-FCXRPNKRSA-N 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 229920001661 Chitosan Polymers 0.000 description 1
- 238000005411 Van der Waals force Methods 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 239000011246 composite particle Substances 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 229940109262 curcumin Drugs 0.000 description 1
- 235000012754 curcumin Nutrition 0.000 description 1
- 239000004148 curcumin Substances 0.000 description 1
- 238000005034 decoration Methods 0.000 description 1
- 229920006237 degradable polymer Polymers 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- VFLDPWHFBUODDF-UHFFFAOYSA-N diferuloylmethane Natural products C1=C(O)C(OC)=CC(C=CC(=O)CC(=O)C=CC=2C=C(OC)C(O)=CC=2)=C1 VFLDPWHFBUODDF-UHFFFAOYSA-N 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 235000012489 doughnuts Nutrition 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 238000005265 energy consumption Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 239000002360 explosive Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 239000000416 hydrocolloid Substances 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 239000003595 mist Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000002159 nanocrystal Substances 0.000 description 1
- 239000007908 nanoemulsion Substances 0.000 description 1
- KVWDHTXUZHCGIO-UHFFFAOYSA-N olanzapine Chemical compound C1CN(C)CCN1C1=NC2=CC=CC=C2NC2=C1C=C(C)S2 KVWDHTXUZHCGIO-UHFFFAOYSA-N 0.000 description 1
- 229960005017 olanzapine Drugs 0.000 description 1
- 229920001606 poly(lactic acid-co-glycolic acid) Polymers 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5107—Excipients; Inactive ingredients
- A61K9/513—Organic macromolecular compounds; Dendrimers
- A61K9/5138—Organic macromolecular compounds; Dendrimers obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
- A61K31/343—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D9/00—Crystallisation
- B01D9/0063—Control or regulation
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D9/00—Crystallisation
- B01D2009/0086—Processes or apparatus therefor
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Physics & Mathematics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Crystallography & Structural Chemistry (AREA)
- Biomedical Technology (AREA)
- Nanotechnology (AREA)
- Optics & Photonics (AREA)
- Separation Using Semi-Permeable Membranes (AREA)
- Medicinal Preparation (AREA)
Abstract
Polymer overmold Nano medication preparation facilities and preparation method, are related to the preparation of Nano medication.Polymer overmold Nano medication preparation facilities is provided with a point solvent bottle, the 1st peristaltic pump, fibre bundle crystallizer, dissolving apothecary jar, the 2nd peristaltic pump and vacuum filtering system；The fibre bundle crystallizer is provided with outer tube and inner tube, inner tube is located in outer tube, solvent bottle is divided to be connected with the entrance of the 1st peristaltic pump, the outlet of the 1st peristaltic pump is connected with the inner tube inlet of fibre bundle crystallizer, the inner tube outlet closure of fibre bundle crystallizer, dissolving apothecary jar is connected with the entrance of the 2nd peristaltic pump, and the outlet of the 2nd peristaltic pump is connected with the outer tube inlet of fibre bundle crystallizer, and the outer tube outlet of fibre bundle crystallizer connects vacuum filtering system；The inner tube of the fibre bundle crystallizer is made up of hollow porous fiber tow.Fibre bundle crystallizer is first prepared, then prepares Nano medication and coated with coated polymer, it is post-treated to obtain final product product.
Description
Technical field
The present invention relates to the preparation of Nano medication, more particularly, to one kind using the crystallization of micron order hollow porous fiber tow
The polymer overmold Nano medication preparation facilities and preparation method of device.
Background technology
In recent years, continuing to develop with nanosecond science and technology, based on nanometer technology research and development nano-drug preparation it is only
Property values are also gradually understood by researcher, such as passive targeting, enhancing infiltration retention effect etc..But directly use nanometer medicine
Thing crystal is difficult to be applied directly in actual therapeutic because of a variety of causes, just by body before Chang Wei arrival human body active components
Macrophage identification in interior immune system is swallowed up and is failed.Using degradable polymer (such as PLGA, PEG etc.) to nanometer
The polymer nanocomposite that grain cladding is made carries medicine particle many advantages：Drug effectiveness can be such as improved, the control release time, is prolonged
Medicine biological half-life long, it is more easy to through cell membrane etc..Therefore how by medicament nano, and cladding is carried out to its surface repair
Decorations turn into a popular research problem for being badly in need of solving.At this stage, Many researchers take distinct methods pair from every field
Nano medication is prepared and polymer overmold.Such as Azad ([1] Azad M, Arteaga C, Abdelmalek B, et
al.Spray drying of drug-swellable dispersant suspensions for preparation of
fast-dissolving,high drug-loaded,surfactant-free nanocomposites.Drug
Development and Industrial Pharmacy,2015,41(10):1-15) will first by wet method nanon ball-mill
Medicine griseofulvin (Griseofulvin) is prepared into a nanometer suspension, polymer and surfactant is subsequently added, using spray
Mist dry technology dries Nano medication suspension cladding turns into polymer nanocomposite composite particles；([2] Li J, the Hwang I such as li
C,Chen X,et al.Effects of chitosan coating on curcumin loaded nano-emulsion:
Study on stability and invitrodigestibility.Food Hydrocolloids,2016,60:138-
147) the nanometer emulsified methods of O/W are utilized, first medicine is dispersed in oil-based system, then instilled in the acetic acid solution of shitosan simultaneously
Emulsified using ultrasound, be prepared into the nano particle suspension of polymer overmold；([3] Paisana M C, the M ü such as Paisana
llers K C,Wahl M A,et al.Production and Stabilization of Olanzapine
Nanoparticles by Rapid Expansion of Supercritical Solutions(RESS).Journal of
Supercritical Fluids the,2015,109(1):124-13) using super-critical rapid expansion method (RESS) in high temperature
Supercritical CO is used under high pressure2Prepare Nano medication particle.But these method for coating all be present.Based on O/W's
Nanometer emulsified method easily in preparation process due to nano particle peculiar property (high-ratio surface energy, strong Van der Waals force) and
Soft-agglomerated phenomenon is produced in solution, the hard aggregation that the polymer overmold of production is lived multiple nano particles and caused cannot be separated；
Supercritical CO2Technology is then because the low solubility of polymer or drug particles causes that the large-scale production of medicine is restricted；Spraying
Dry technology needs the energy consumption condition high such as high temperature, and nanometer particle size to preparing is restricted, it is difficult to prepare less than 10nm
Grain；And most of preparation method is all batch production (batch process) at this stage, cause production efficiency low, often
A batch of quality is uneven, it is difficult to carry out Effective Regulation in practical application.Therefore how successional grain is produced
Degree is controllable, and reaction condition is gentle and polymer overmold Nano medication particle of steady quality turns into the emphasis and difficulty of research at present
Point.
The content of the invention
It is an object of the invention to provide a kind of polymer overmold of utilization micron order hollow porous fiber tow crystallizer
Nano medication preparation facilities.
Another object of the present invention is to provide a kind of preparation method of polymer overmold Nano medication.
The polymer overmold Nano medication preparation facilities be provided with a point solvent bottle, the 1st peristaltic pump, fibre bundle crystallizer,
Dissolving apothecary jar, the 2nd peristaltic pump and vacuum filtering system；The fibre bundle crystallizer is provided with outer tube and inner tube, and inner tube is located at
In outer tube, a point solvent bottle is connected with the entrance of the 1st peristaltic pump, and outlet and the inner tube of fibre bundle crystallizer of the 1st peristaltic pump enter
Mouth connection, the inner tube outlet closure of fibre bundle crystallizer, dissolving apothecary jar is connected with the entrance of the 2nd peristaltic pump, the 2nd peristaltic pump
Outlet be connected with the outer tube inlet of fibre bundle crystallizer, the outlet of the outer tube of fibre bundle crystallizer connects vacuum filtering system；
The inner tube of the fibre bundle crystallizer is made up of hollow porous fiber tow.
The 1st pressure gauge, described can be set between the outlet of the 1st peristaltic pump and the inner tube inlet of fibre bundle crystallizer
The 2nd pressure gauge can be set between the outlet of 2 peristaltic pumps and the outer tube inlet of fibre bundle crystallizer；Single hollow porous fiber silk
Porosity can be 80%.
The preparation method of the polymer overmold Nano medication, using the polymer overmold Nano medication preparation facilities,
The preparation method is comprised the following steps：
1) fibre bundle crystallizer is prepared：Single bundle hollow porous fiber silk is cut, is loaded into sleeve pipe, constitute fiber
Tow, closes the inner tube outlet of fibre bundle crystallizer, to prevent fluid from being flowed out from the inner tube outlet of fibre bundle crystallizer；
In step 1) in, single bundle hollow porous fiber silk can be single using 30 PDVF hollow porous fibers silks
The length of PDVF hollow porous fibers silk can be 20cm, and internal diameter can be 600 μm, and the porosity of inwall can be 80%, and aperture can be
500nm (Parameter adjustable to adapt to the controlledly synthesis of Nano medication)；Described sleeve pipe can use PP sleeve pipes, and the internal diameter of sleeve pipe can be
3cm。
2) preparation of Nano medication and polymer overmold：Load a point solvent in point solvent bottle, will divide molten by the 1st peristaltic pump
The inner tube inlet of fibre bundle crystallizer is sent into agent, and the inner tube outlet due to fibre bundle crystallizer is blocked so that point solvent
Extruded outward by the inwall aperture of the fibre bundle in the inner tube of fibre bundle crystallizer；The outer tube of fibre bundle crystallizer exists
The same time is introduced into the acetone soln of the dissolving medicine and polymer in dissolving apothecary jar, fibre bundle crystallization by the 2nd peristaltic pump
The microring array environment that point solvent that the inner tube of device is extruded outward is createed in a large amount of apertures of the outer tube of fibre bundle crystallizer
In uniformly mix with drug solution at outer tube because during point solvent can effectively reduce the acetone soln of dissolving medicine and polymer
Solute solubility so that it is nano medicine crystal that medicine is first separated out from acetone soln, and post-consumer polymer is due to heterogeneous nucleation
Separate out and be coated on nano medicine crystal, realize preparation and the polymer overmold of Nano medication；
In step 2) in, described point of solvent can use deionized water；It is described that point solvent is sent into filament by the 1st peristaltic pump
The speed of the inner tube inlet of beam crystallizer can be 5ml/min；The outer tube of the fibre bundle crystallizer is compacted by the 2nd in the same time
The speed that dynamic pump is introduced into the acetone soln of the dissolving medicine and polymer in dissolving apothecary jar can be 5ml/min；The medicine can
Using griseofulvin (Griseofulvin), the polymer can use acrylic resin (Eudragit)；Fibre bundle is crystallized
The structural parameters and reaction condition of device can precise control Nano medication particle particle size and coating thickness.
3) post-process：The nano medicine crystal of polymer overmold and the dissolving medicine of excess and the acetone soln of polymer with
Divide solvent to be discharged by the outer tube outlet of fibre bundle crystallizer, collection of products is carried out into vacuum filtering system, be collected into
Nanometer filter cake obtains final product polymer overmold Nano medication by being vacuum dried after ultrasound filtration.
In step 3) in, the vacuum filtering system can use PVDF filter paper using nanofiltration membrane, the nanofiltration membrane,
The PVDF filter paper can be using the PVDF filter paper GVWP04700 of Millipore 220nm；The time of the ultrasound filtration can be
20min。
Compared with existing polymer overmold Nano medication preparation facilities and preparation method, the present invention has following prominent excellent
Point：
1) particle diameter of precise control Nano medication and polymer covering layer thickness：Micron order doughnut tow is special because of its
Tectonic property can provide the microenvironment needed beneficial to crystallization.The pore (being more than 80% porosity) of wherein porous fibre silk causes big
Amount introduction point can provide uniform radial direction Mixed Zone for point solvent by the mixing with organic solution.Guided for point solvent
Precipitation process, the quick mixed process between two fluids affects the local degree of supersaturation of precipitation zone, and efficiently accurate
Mixed process can cause explosive nucleation and make homoepitaxial after crystal nucleation, so as to reach precise control nanocrystal particle diameter
With the purpose of coating thickness (10nm).
2) the fibre bundle crystallizer that the present invention is used is a kind of continuous type crystallizer, fibre bundle crystallizer internal-response
It is continuous type course of reaction, for being produced compared to batch, can in time by regulating and controlling response parameter integration production size tunable
Polymer nanocomposite medicine crystal, is conducive to increasing yield and control product quality, can effectively eliminate condition difference between batch and lead
The problems such as unstable product quality of cause.
3) it is easy to amplify production：Fibre bundle crystallizer of the invention, can due to the special construction of internal fibre bundle
Amplify the purpose of production to be reached by simply increasing internal tow quantity.
Brief description of the drawings
Fig. 1 is the single hollow porous fiber silk knot of polymer overmold Nano medication preparation facilities embodiment of the present invention
Structure schematic diagram.
Fig. 2 is that the fibre bundle mold structure of polymer overmold Nano medication preparation facilities embodiment of the present invention shows
It is intended to.
Fig. 3 is the structural representation of polymer overmold Nano medication preparation facilities embodiment of the present invention.
Specific embodiment
Following examples will the present invention is further illustrated with reference to accompanying drawing.
Referring to Fig. 1~3, the polymer overmold Nano medication preparation facilities embodiment is provided with the wriggling of point solvent bottle the 1, the 1st
Pump 2, fibre bundle crystallizer, dissolving apothecary jar 4, the 2nd peristaltic pump 5 and vacuum filtering system 6；The fibre bundle crystallizer sets
There are outer tube 301 and inner tube 302, inner tube 302 is located in outer tube 301；Solvent bottle 1 is divided to be connected with the entrance of the 1st peristaltic pump 2, the 1st is compacted
The outlet of dynamic pump 2 is connected with the inner tube inlet 31 of fibre bundle crystallizer, and the inner tube outlet 32 of fibre bundle crystallizer is blocked, molten
Solution apothecary jar 4 is connected with the entrance of the 2nd peristaltic pump 5, the outlet of the 2nd peristaltic pump 5 and the outer tube inlet 33 of fibre bundle crystallizer
Connection, the outer tube outlet 34 of fibre bundle crystallizer connects vacuum filtering system 6；The inner tube 302 of the fibre bundle crystallizer by
Hollow porous fiber tow is constituted.Can be set between the outlet of the 1st peristaltic pump 2 and the inner tube inlet 31 of fibre bundle crystallizer
1st pressure gauge 7, the 2nd pressure gauge can be set between the outlet of the 2nd peristaltic pump 5 and the outer tube inlet 33 of fibre bundle crystallizer
8；The porosity of single hollow porous fiber silk can be 80%.
The preparation method of the polymer overmold Nano medication given below, using the polymer overmold Nano medication system
Standby device, the preparation method is comprised the following steps：
1) fibre bundle crystallizer is prepared：Single bundle hollow porous fiber tow is cut, is loaded into sleeve pipe, constituted fine
Dimension tow, closes the inner tube outlet of fibre bundle crystallizer, to prevent fluid from being flowed out from the inner tube outlet of fibre bundle crystallizer；
Single bundle hollow porous fiber tow is using 30 PDVF hollow porous fibers silks, the length of single PDVF hollow porous fibers silk
It is 20cm to spend, and internal diameter is 600 μm, and the porosity of inwall is 80%, and aperture is that (Parameter adjustable is to adapt to Nano medication for 500nm
Controlledly synthesis)；Described sleeve pipe uses PP sleeve pipes, and the internal diameter of sleeve pipe is 3cm.
2) preparation of Nano medication and polymer overmold：Load deionized water in point solvent bottle, will be divided by the 1st peristaltic pump
Solvent sends into the inner tube inlet of fibre bundle crystallizer, and the inner tube outlet due to fibre bundle crystallizer blocked so that go from
Sub- water is extruded outward by the inwall aperture of the fibre bundle in the inner tube of fibre bundle crystallizer；Outside fibre bundle crystallizer
The acetone soln of dissolving medicine and polymer of the pipe in the same time is introduced into dissolving apothecary jar by the 2nd peristaltic pump, fibre bundle
The microring array that the deionized water that the inner tube of crystallizer is extruded outward is formed in a large amount of apertures of the outer tube of fibre bundle crystallizer
Uniformly mix with drug solution at outer tube in environment, because deionized water can effectively reduce dissolving medicine and the acetone of polymer is molten
Solute solubility in liquid so that it is nano medicine crystal that medicine is first separated out from acetone soln, and post-consumer polymer is due to heterogeneous
Nucleation and separate out and be coated on nano medicine crystal, realize preparation and the polymer overmold of Nano medication；It is described to be wriggled by the 1st
The speed of the inner tube inlet of deionized water feeding fibre bundle crystallizer is 5ml/min by pump；The fibre bundle crystallizer
The speed of the acetone soln of dissolving medicine and polymer of the outer tube in the same time is introduced into dissolving apothecary jar by the 2nd peristaltic pump can
It is 5ml/min；The medicine uses griseofulvin (Griseofulvin), the polymer to use acrylic resin
(Eudragit)；The structural parameters and reaction condition of fibre bundle crystallizer can precise control Nano medication particle particle diameter
Size and coating thickness.
3) post-process：The nano medicine crystal of polymer overmold and the dissolving medicine of excess and the acetone soln of polymer with
Deionized water is discharged by the outer tube outlet of fibre bundle crystallizer, and collection of products is carried out into vacuum filtering system, is collected into
Nanometer filter cake by being vacuum dried after ultrasound filtration, obtain final product polymer overmold Nano medication；The vacuum filtering system
Using nanofiltration membrane, the nanofiltration membrane is the PVDF filter paper GVWP04700 of Miliopore 220nm；The ultrasound filtration
Time is 20min.
Claims (10)
1. polymer overmold Nano medication preparation facilities, it is characterised in that be provided with a point solvent bottle, the 1st peristaltic pump, filament binding
Brilliant device, dissolving apothecary jar, the 2nd peristaltic pump and vacuum filtering system；The fibre bundle crystallizer is provided with outer tube and inner tube, inner tube
It is located in outer tube, a point solvent bottle is connected with the entrance of the 1st peristaltic pump, and the outlet of the 1st peristaltic pump is interior with fibre bundle crystallizer
Tube inlet is connected, and the inner tube outlet closure of fibre bundle crystallizer, dissolving apothecary jar is connected with the entrance of the 2nd peristaltic pump, and the 2nd is compacted
The outlet of dynamic pump is connected with the outer tube inlet of fibre bundle crystallizer, and the outer tube outlet of fibre bundle crystallizer meets vacuum filter system
System；The inner tube of the fibre bundle crystallizer is made up of hollow porous fiber tow.
2. polymer overmold Nano medication preparation facilities as claimed in claim 1, it is characterised in that the outlet of the 1st peristaltic pump
The 1st pressure gauge is set and the inner tube inlet of fibre bundle crystallizer between.
3. polymer overmold Nano medication preparation facilities as claimed in claim 1, it is characterised in that the outlet of the 2nd peristaltic pump
The 2nd pressure gauge is set and the outer tube inlet of fibre bundle crystallizer between.
4. polymer overmold Nano medication preparation facilities as claimed in claim 1, it is characterised in that single hollow porous fiber silk
Porosity be 80%.
5. the preparation method of polymer overmold Nano medication, it is characterised in that using the polymer overmold as described in Claims 1 to 4
Nano medication preparation facilities, the preparation method is comprised the following steps：
1) fibre bundle crystallizer is prepared：Single bundle hollow porous fiber silk is cut, is loaded into sleeve pipe, constitute filament
Beam, closes the inner tube outlet of fibre bundle crystallizer, to prevent fluid from being flowed out from the inner tube outlet of fibre bundle crystallizer；
2) preparation of Nano medication and polymer overmold：Load a point solvent in point solvent bottle, sent a point solvent by the 1st peristaltic pump
Enter the inner tube inlet of fibre bundle crystallizer, divide solvent by the inwall aperture of the fibre bundle in the inner tube of fibre bundle crystallizer
Place extrudes outward；Dissolving medicine of the outer tube of fibre bundle crystallizer in the same time is introduced into dissolving apothecary jar by the 2nd peristaltic pump
The acetone soln of thing and polymer, point solvent that the inner tube of fibre bundle crystallizer is extruded outward is in the outer of fibre bundle crystallizer
Mix with drug solution at outer tube in the microring array environment that a large amount of apertures of pipe are formed, nanometer medicine is first separated out from acetone soln
Thing crystal, and post-consumer polymer is separated out due to heterogeneous nucleation and is coated on nano medicine crystal, realizes the preparation of Nano medication
With polymer overmold；
3) post-process：The nano medicine crystal of polymer overmold with excess dissolving medicine and polymer acetone soln with divide it is molten
Agent is discharged by the outer tube outlet of fibre bundle crystallizer, carries out collection of products into vacuum filtering system, the nanometer being collected into
Filter cake obtains final product polymer overmold Nano medication by being vacuum dried after ultrasound filtration.
6. the preparation method of polymer overmold Nano medication as claimed in claim 5, it is characterised in that in step 1) in, the list
Bundle hollow porous fiber silk is using 30 PDVF hollow porous fibers silks.
7. the preparation method of polymer overmold Nano medication as claimed in claim 5, it is characterised in that in step 1) in, it is single
The length of PDVF hollow porous fibers silk is 20cm, and internal diameter is 600 μm, and the porosity of inwall is 80%, and aperture is 500nm；Institute
Stating sleeve pipe can be using PP sleeve pipe, and the internal diameter of sleeve pipe can be 3cm.
8. the preparation method of polymer overmold Nano medication as claimed in claim 5, it is characterised in that in step 2) in, described point
Solvent uses deionized water；The speed of the inner tube inlet that point solvent is sent into fibre bundle crystallizer by the 1st peristaltic pump can
It is 5ml/min；Dissolving of the outer tube of the fibre bundle crystallizer in the same time is introduced into dissolving apothecary jar by the 2nd peristaltic pump
The speed of the acetone soln of medicine and polymer can be 5ml/min.
9. the preparation method of polymer overmold Nano medication as claimed in claim 5, it is characterised in that in step 2) in, the medicine
Thing uses griseofulvin, the polymer to use acrylic resin.
10. the preparation method of polymer overmold Nano medication as claimed in claim 5, it is characterised in that in step 3) in, it is described
Vacuum filtering system uses nanofiltration membrane, and the nanofiltration membrane uses the PVDF filter paper, the PVDF filter paper can to use Millipore
The PVDF filter paper GVWP04700 of 220nm；The time of the ultrasound filtration can be 20min.
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| CN113493220A (en) * | 2020-04-02 | 2021-10-12 | 杨洋 | Hollow metal oxide microsphere, preparation method thereof and drug sustained-release application |
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