CN106139943B - A kind of membrane emulsifier and emulsion preparation method - Google Patents
A kind of membrane emulsifier and emulsion preparation method Download PDFInfo
- Publication number
- CN106139943B CN106139943B CN201610495156.0A CN201610495156A CN106139943B CN 106139943 B CN106139943 B CN 106139943B CN 201610495156 A CN201610495156 A CN 201610495156A CN 106139943 B CN106139943 B CN 106139943B
- Authority
- CN
- China
- Prior art keywords
- dispersed phase
- membrane
- fluid reservoir
- continuous phase
- flow
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
- B01F23/00—Mixing according to the phases to be mixed, e.g. dispersing or emulsifying
- B01F23/40—Mixing liquids with liquids; Emulsifying
- B01F23/41—Emulsifying
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
- B01F33/00—Other mixers; Mixing plants; Combinations of mixers
- B01F33/45—Magnetic mixers; Mixers with magnetically driven stirrers
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J13/00—Colloid chemistry, e.g. the production of colloidal materials or their solutions, not otherwise provided for; Making microcapsules or microballoons
- B01J13/02—Making microcapsules or microballoons
Abstract
A kind of membrane emulsifier of present invention offer and emulsion preparation method, are related to film emulsification field, and device includes：Stablize to pressure device and film emulsifier unit, film emulsifier unit includes conventional film emulsifier unit and high flux membrane emulsifier unit, conventional film emulsifier unit and high flux membrane emulsifier unit are connect with stable to pressure device by double valve respectively, stablize and be set to controller for liquid flow to press fitting, it includes flowmeter, dispersed phase feeding equipment and constant flow pump to stablize to pressure device.Present invention fluid flow, which controls, replaces the gas pressure of existing membrane emulsifier to control, and avoids the use of nitrogen cylinder, simplifies equipment part, facilitate the operation and transport of instrument；The accuracy controlling for realizing transmembrane pressure, improves the stability of transmembrane pressure, ensures the uniform particle diameter and batch repeatability of drop; conducive to carry out standardization and large-scale production; preparation process mild condition can be used for the embedding etc. of bioactive substance or labile drug, applied widely.
Description
Technical field
The present invention provide a kind of pressure accurately control, pressure stability, membrane emulsifier easy to operate and lotion preparation side
Method is related to film emulsification field.
Background technology
Emulsification is the significant element operation in the fields such as chemistry, chemical industry, light industry, food, medicine, biochemistry.Currently, general use
The methods of mechanical agitation, homogeneous and ultrasound prepare emulsion and microballoon, although process conditions are simple, uniform particle diameter is poor, grain
Diameter size is difficult to control, and experimental repeatability is poor.
In order to prepare the lotion and nano-microspheres product of uniform particle diameter, film emulsifying technology developed rapidly in recent years.The technology exists
The particle size of lotion can not only be controlled in preparation process, and particle diameter distribution is uniform, mild condition and energy consumption is relatively low, product weight
Renaturation is good, is widely used in the every field such as food, cosmetics, medicine and bio-separation in recent years.
SPG Technology Co., Ltd. of Japan develops a kind of conventional membrane emulsifier, and operating procedure is：First by microporous barrier
Pipe installs, and then dispersion is added in fluid reservoir, the pipeline and nitrogen cylinder being connected to above fluid reservoir, and keeps entire gas circuit
Closed no leakage adjusts continuous phase stir speed (S.S.), opens nitrogen pressure valve, slowly increases pressure, when lotion generates, this pressure is
For critical pressure, keeps this pressure that dispersed phase is pressed into outer aqueous phase by fenestra and form emulsion droplets, in the process, it is necessary to tight
Lattice keep the stability of nitrogen pressure.Because the size of membrane pressure has the grain size of emulsion droplets, particle diameter distribution and formation important
It influences.Cause dispersed phase to be injected into continuous phase if membrane pressure crosses conference, forms large-sized emulsion droplets；If membrane pressure mistake
It is small to lead to film emulsion process overlong time, influence production efficiency.Moreover, with the progress of emulsification, the reduction of dispersed phase liquid level
It can cause the fluctuation of pressure.Meanwhile the control of the pressure such as pressurization, release of emulsifier is manual operation, also easily leads to pressure not
Stablize.Meanwhile the pressure needed when preparing big grain size microballoon using membrane emulsifier is very low, the precision and pressure to pressure gauge it is steady
Qualitative requirement is higher, has prodigious challenge to device operator.
Chinese patent document 200810223283.0 (notification number CN101683592) discloses a kind of membrane emulsifier, including
Membrane module, dispersed phase head tank, voltage stabilizing feed device and continuous phase head tank；The voltage stabilizing feed device that the invention provides realizes
Lotion high-caliber batch repeatability, effectively increase the quality of lotion, but the membrane emulsifier still uses gas to pressure device
Pressure mode, pressure transient are given, although improving pressure stability with voltage stabilizing feed device, voltage stabilizing feed device is generally foreign countries
Inlet device, price costly, increase the cost of instrument, it is difficult to realize industrialization.
The major defect of the prior art is that dispersed phase transmembrane pressure derives from gas pressure, and size is adjusted to manually grasp
Make, the precision and stability of pressure is difficult to control, to make microballoon grain size and batch repeatability by device operator experience
It is affected, it is difficult to carry out standardization and large-scale production.Accordingly, it is desirable to provide a kind of pressure can accuracy controlling, pressure stability,
Novel membrane emulsifier easy to operate, conducive to progress industrialized production.
Invention content
The purpose of the present invention be exactly solve the disadvantage that in the prior art, provide a kind of pressure can accuracy controlling, pressure stability,
Membrane emulsifier and emulsification method easy to operate, conducive to progress industrialized production.
Technical scheme is as follows：
To solve the above-mentioned problems, the present invention provides a kind of membrane emulsifier, is controlled with fluid flow and existing film is replaced to emulsify
The gas pressure of device controls, and realizes the accuracy controlling of pressure and improves pressure stability.
A kind of membrane emulsifier, including stablize to pressure device and film emulsifier unit, film emulsifier unit includes conventional film emulsification dress
It sets and gives pressure with stable by double valve respectively with high flux membrane emulsifier unit, conventional film emulsifier unit and high flux membrane emulsifier unit
Device connects, and stablizes and is set to controller for liquid flow to press fitting, and it includes flowmeter, dispersed phase feeding equipment to stablize to pressure device
And constant flow pump.
According to currently preferred, the flow is calculated as fluid flowmeter, and fluid flow is calculated as differential pressure flowmeter, electromagnetism
One kind in flowmeter, mass flowmenter, the constant flow pump be can accuracy controlling flow velocity syringe pump or peristaltic pump.
It is further preferred that the dispersed phase feeding equipment includes syringe, syringe one end is connected with syringe pump, injection
The device other end is connected with flowmeter；Or the dispersed phase feeding equipment includes beaker, beaker is connected by peristaltic pump with flowmeter.
It is further preferred that the syringe pump is single channel syringe pump or multichannel injection pump.
It is further preferred that the maximum flow rate of the constant flow pump is selected according to the aperture of micropore membrane tube, maximum flow rate range
For 10 μ L/min-43.35mL/min.
It is further preferred that depending on the volume of the dispersed phase feeding equipment is needed because of different experiments, range 1-
200mL。
According to currently preferred, film emulsifier unit includes dispersed phase fluid reservoir, membrane module, continuous phase fluid reservoir and continuous
Phase flow device, membrane module include micropore membrane tube and dispersed phase cavity；
Conventional film emulsifier unit includes the first dispersed phase fluid reservoir, the first membrane module, the first continuous phase fluid reservoir, continuous phase
Flow device；First membrane module include the first micropore membrane tube and the first dispersed phase cavity, the first dispersed phase cavity by
The plate washer of first micropore membrane tube upper and lower ends is tightly connected to form first with the housing liquid being enclosed in outside the first micropore membrane tube
Dispersed phase cavity, the first dispersed phase cavity are equipped with dispersed phase entrance and air bleeding valve, and dispersed phase entrance passes through stainless steel screw thread and close
Seal is connected to the discharge port of the first dispersed phase fluid reservoir；
High flux membrane emulsifier unit, including the second dispersed phase fluid reservoir, the second membrane module, the second continuous phase fluid reservoir, company
Continuous phase flow device, the second membrane module include the second micropore membrane tube and the second dispersed phase cavity, and the second dispersed phase cavity, which is equipped with, to be divided
Dephasing entrance and air bleeding valve, the second dispersed phase cavity further include that the continuous phase at both ends goes out muzzle, continuous phase into muzzle, continuous phase
Go out muzzle into muzzle, continuous phase to connect by stainless steel screw thread and sealing ring with the second dispersed phase cavity.
It is further preferred that continuous phase flow device is magnetic stirring apparatus or drives the pump of continuous phase flowing, pump to wriggle
Pump or electromagnetic pump.
It is further preferred that the first micropore membrane tube, the second micropore membrane tube are hydrophily membrane tube or hydrophobicity membrane tube,
Since membrane tube material is different, including be SPG (Shirasu Porous Glass) film, ceramic membrane, metal film, polymeric membrane and
Microporous barrier molecular sieve, the first micropore membrane tube, the second micropore membrane tube aperture include 2 μm, 5 μm, 10 μm, 20 μm, 50 μm.
It is further preferred that the inside of the dispersed phase fluid reservoir is conical cavity or cylindrical cavity, inner surface is
Smooth surface, dispersed phase fluid reservoir are dispersed phase fluid reservoir prepared by stainless steel, and upper capping is equipped with above dispersed phase fluid reservoir, on
Sealing ring is equipped between capping and dispersed phase fluid reservoir, to ensure sealing without leakage, upper capping is equipped with aperture, and upper capping passes through small
Hole is connected with the stable outlet to pressure device, and the tank mouth of dispersed phase fluid reservoir is quick coupling with upper capping, ensures leakproofness, easily
Operation.
It is further preferred that the second continuous phase fluid reservoir includes being sent into the continuous of continuous phase to the second micropore membrane tube
Phase feed pipe and the continuous phase return duct that continuous phase flows back.
The present invention also provides a kind of methods preparing lotion using above-mentioned membrane emulsifier, include the following steps：
(1) the dispersed phase flow rates of different pore size micropore membrane tube are measured：The micropore membrane tube in a certain aperture is selected, it is to be installed
After good, lower flow parameters are set, observation dispersed phase be able to stablize dispersed phase across micropore across the state of micropore membrane tube
Flow velocity when membrane tube is set as critical flow velocity；The flow velocity for gradually increasing dispersed phase, by dispersed phase just with pattern across micropore
Flow velocity when membrane tube is set as maximum flow rate, then the dispersed phase flow rates for measuring the micropore membrane tube in this aperture are critical flow velocity to most
Between big flow velocity；
(2) lotion of uniform particle sizes is prepared：After micropore membrane tube installs, dispersed phase is filled it up with into dispersion feeding equipment, is divided
In dephasing fluid reservoir and dispersed phase cavity, will it continuously be added to continuous phase fluid reservoir, the magnetic agitation speed of magnetic stirring apparatus is set
Degree opens the pump for driving continuous phase flowing, and setting is stablized to the dispersed phase flow parameters of constant flow pump in pressure device, and the parameter is made
In the dispersed phase flow rates in step (1), dispersed phase enters continuous phase with stable state across micropore membrane tube, obtains liquid
Drip the uniform lotion of particle diameter distribution.
The beneficial effects of the present invention are：
1, the present invention is stablized by being arranged to pressure device, and the gas pressure for replacing existing membrane emulsifier is controlled with fluid flow
Control, dispersed phase flow velocity is accurately adjusted using constant flow pump accurately to change dispersed phase transmembrane pressure, realizes the accurate of transmembrane pressure
Regulation and control, improve the stability of transmembrane pressure, ensure the uniform particle diameter and batch repeatability of drop.
2, the present invention provides through setting flowermeter, disperse phase flow state is monitored in real time.Meanwhile existing gas is given
Pressure device is usually nitrogen cylinder and pressure valve, common nitrogen bottle height 145cm, and weight 50.5kg, occupied space is big, be not easy to move and
Transport, and stabilization provided by the invention gives pressure device high 10cm, weight 3.6kg, small, simple light, simplified film emulsifying device
Accessory facilitates the operation and transport of instrument, conducive to standardization and large-scale production is carried out.
3, using membrane emulsifier provided by the invention prepare drop/Microsphere Size is uniform, size tunable, batch repeatability
It is good, and preparation process mild condition, it can be used for the embedding etc. of bioactive substance or labile drug.Film provided by the invention
Emulsifier is easy to operate, applied widely, can be used for preparing all common lotions or the microballoons such as W/O/W types, O/W types and w/o type
Preparation system.
Description of the drawings
Fig. 1 is the structural schematic diagram of inventive film emulsifier；
Fig. 2 a are that 1 membrane emulsifier of the embodiment of the present invention is stablized to the schematic diagram of pressure device；
Fig. 2 b are that 2 membrane emulsifier of the embodiment of the present invention is stablized to the schematic diagram of pressure device；
Fig. 3 is the microballoon result figure that in the embodiment of the present invention 3 prepared by membrane emulsifier；A in Fig. 31、A2For different enlargement ratios
Emulsion droplet microscope photo, B in Fig. 31、B2For the microballoon stereoscan photograph of different enlargement ratios；
Fig. 4 is the microballoon result figure prepared using existing conventional membrane emulsifier in comparative example；A in Fig. 41、A2For different amplifications
The microscope photo of the emulsion droplet of multiplying power, B in Fig. 41、B2For the microballoon stereoscan photograph of different enlargement ratios；
Wherein：1, stablize to pressure device, 2, upper capping, the 3, first dispersed phase fluid reservoir, 4, conventional film emulsifier unit, 5, the
One continuous phase fluid reservoir, the 6, first dispersed phase cavity, the 7, first micropore membrane tube, 8, magneton, 9, magnetic stirring apparatus, 10, double valve,
11, air bleeding valve, the 12, second dispersed phase fluid reservoir, 13, lower capping, 14, high flux membrane emulsifier unit, the 15, second dispersed phase chamber
Body, the 16, second micropore membrane tube, 17, continuous phase feed pipe, 18, continuous phase return duct, the 19, second continuous phase fluid reservoir, 20, compacted
Dynamic pump, 21, syringe, 22, plate washer after syringe pump, 23, syringe pump front baffle board, 24, syringe pump, 25, flowmeter, 26, beaker,
27, peristaltic pump feed pipe, 28, peristaltic pump, 29, peristaltic pump discharge nozzle.
Specific implementation mode
The present invention will be further described by way of example and in conjunction with the accompanying drawings, but not limited to this.
Embodiment 1：
The present invention provides a kind of membrane emulsifier, as shown in Figure 1, the equipment includes stablizing to pressure device 1, conventional film emulsification dress
Set 4 and high flux membrane emulsifier unit 14.Conventional film emulsifier unit 4 and high flux membrane emulsifier unit 14 respectively by double valve 10 with
Stablize and connected to pressure device 1, it is that fluid flow is controlled to pressure device to stablize to pressure device 1, and it includes flow to stablize to pressure device 1
Meter, dispersed phase feeding equipment and constant flow pump.
Wherein, stablize it is as shown in Figure 2 a to pressure device 1, including sequentially connected syringe pump 24, dispersed phase feeding equipment and
Flowmeter 25, syringe pump are single channel syringe pump, and flow is calculated as differential pressure flowmeter, and dispersed phase feeding equipment is syringe 21,
It is fixedly connected by syringe pump front apron 23 and syringe pump rear baffle 22 between single channel syringe pump and syringe, flowmeter and note
Emitter connects, and monitors the actual flow velocity of dispersed phase in real time, ensures the stability of disperse phase flow.
Film emulsifier unit includes dispersed phase fluid reservoir, membrane module, continuous phase fluid reservoir and continuous phase flow device, membrane module
Including micropore membrane tube and dispersed phase cavity；To distinguish conventional film emulsifier unit and high flux membrane emulsifier unit, with the first, secondth area
Divide name.
Conventional film emulsifier unit 4 include from top to bottom connect the first dispersed phase fluid reservoir 3, the first continuous phase fluid reservoir 5,
First dispersed phase cavity 6, the first micropore membrane tube 7, continuous phase flow device, continuous phase flow device include 9 He of magnetic stirring apparatus
Magneton 8；First dispersed phase cavity by the first micropore membrane tube upper and lower ends plate washer and be enclosed in outside the first micropore membrane tube
Housing liquid is tightly connected to form the first dispersed phase cavity, and the first dispersed phase cavity is equipped with dispersed phase entrance and air bleeding valve 11, dispersion
Phase entrance is connected to by stainless steel screw thread and sealing ring with the discharge port of the first dispersed phase fluid reservoir, air bleeding valve 11 excluding plus
Expect the bubble generated in the process.
The inside of first dispersed phase fluid reservoir 3 is conical cavity, and inner surface is smooth surface, and the first dispersed phase fluid reservoir is
First dispersed phase fluid reservoir prepared by stainless steel, 3 top of the first dispersed phase fluid reservoir is equipped with upper capping 2, upper to cover 2 and first point
Sealing ring is accompanied between dephasing fluid reservoir 3, using quick coupling, ensures leakproofness, it is easy to operate.Upper capping 2 is equipped with aperture, and steady
The fixed outlet to pressure device is connected.
High flux membrane emulsifier unit 14 includes the second dispersed phase fluid reservoir 12 of connection, the second dispersed phase cavity 15, second
Micropore membrane tube 16, the second continuous phase fluid reservoir 19 and continuous phase flow device, continuous phase flow device are peristaltic pump 20.
Wherein, the second dispersed phase cavity 15 is equipped with dispersed phase entrance and air bleeding valve 11, and air bleeding valve 11 is excluding to feed
The bubble generated in journey.Second dispersed phase fluid reservoir 12 be circular cylindrical cavity, including it is upper capping 2 and it is lower capping 13, it is upper capping 2 with
Gasket is accompanied between second dispersed phase fluid reservoir 12, between 13 and second dispersed phase fluid reservoir 12 of lower capping, using fast quick access
Head connection.Upper capping 2 is equipped with aperture, is connected to the outlet of pressure device with stablizing.Second dispersed phase cavity further includes at both ends
Continuous phase goes out muzzle into muzzle, continuous phase, and continuous phase goes out muzzle with the second dispersed phase cavity by stainless into muzzle, continuous phase
Steel screw thread is connected with sealing ring.
Wherein, the second continuous phase fluid reservoir 19 further includes the continuous phase feed pipe 17 that continuous phase is sent into the second micropore membrane tube
With the continuous phase return duct 18 that continuous phase flows back.
In addition, micropore membrane tube is hydrophily SPG membrane tubes, the micropore membrane tube specification is：The length of first micropore membrane tube is
20mm, aperture are 2 μm, and the length of the second micropore membrane tube is 125mm, and aperture is 2 μm.
Embodiment 2：
The present embodiment provides a kind of pressure stability, easily operated membrane emulsifier, structure is as described in Example 1, not with it
It is with place：Stablize it is as shown in Figure 2 b to pressure device 1, including sequentially connected flowmeter 25, peristaltic pump 28 and dispersed phase into
Expect that device, dispersed phase feeding equipment are beaker 26.Flowmeter 25 monitors the flow velocity of dispersed phase in real time, ensures the steady of disperse phase flow
Qualitative, peristaltic pump 28 is by dispersed phase by dispersed phase feeding equipment through peristaltic pump feed pipe 27, peristaltic pump discharge nozzle 29 and flowmeter
25 are transported to the dispersed phase fluid reservoir of film emulsifier unit.
Embodiment 3：
The present embodiment provides a kind of pressure stability, easily operated membrane emulsifier, structure is as described in Example 1, not with it
It is with place：Syringe pump is multichannel injection pump.
Embodiment 4：
The present embodiment provides a kind of emulsification methods preparing O/W type lotions using the membrane emulsifier.By the PLGA of 2.0g
(nLA:nGA=70:30, Mw=10,0000) it is dissolved in 40mL dichloromethane, as dispersed phase (oil phase)；2.0g PVA are dissolved
In ultra-pure water, as continuous phase (water phase).2 μm of micropore membrane tubes of selected hydrophily, after hydrophily μm micropore membrane tube installs,
Lower flow parameters are set, observation dispersed phase be able to stablize dispersed phase across micropore membrane tube across the state of micropore membrane tube
When flow velocity be set as critical flow velocity；The flow velocity for gradually increasing dispersed phase, by dispersed phase just with pattern across micropore membrane tube
When flow velocity be set as maximum flow rate, then the dispersed phase flow rates for measuring the micropore membrane tube in this aperture are critical flow velocity to max-flow
Between speed；
Dispersed phase feeding equipment, dispersed phase fluid reservoir and dispersed phase cavity is added in PLGA solution, opens air bleeding valve, will be divided
Air is discharged in dephasing cavity, and PLGA solution is made to be full of dispersed phase cavity.Then, continuous phase fluid reservoir is added in PVA aqueous solutions,
Setting magnetic stirring apparatus rotating speed is 150rpm, and dispersed phase feeding equipment is fixed on constant flow pump, the dispersed phase of constant flow pump is arranged
Flow velocity is 20mL/h, feed volume 8mL, and selection starts to feed, and what dispersed phase was stablized presses through micropore film device, by continuous phase band
It walks, obtains PLGA lotions, the microscope photo such as the A in Fig. 3 of drop1、A2It is shown.Then, lotion is stirred at room temperature
Organic solvent dichloromethane is removed for 24 hours, then through centrifuge washing, freeze-drying obtains PLGA microballoons, and the scanning electron microscope of microballoon is shone
B in piece such as Fig. 31、B2It is shown.
Embodiment 5：
The present embodiment provides a kind of emulsification methods preparing w/o type lotion using the membrane emulsifier.The gelatin of 2.0g is molten
It in 18.0g ultra-pure waters, is heated 1 hour in 45 DEG C of water-baths, after gelatin is completely dissolved, as dispersed phase (water phase)；It will
1.0g sorbitan fatty esters (Span80) are dissolved in the paraffin oil of 350mL, fully as continuous phase (oil after dissolving
Phase).Selected 5 μm of micropore membrane tubes of hydrophobicity set lower flow parameters after 5 μm of micropore membrane tubes of hydrophobicity install, and observe
For dispersed phase across the state of micropore membrane tube, flow velocity when dispersed phase be able to be stablized across micropore membrane tube is set as critical flow velocity；By
The flow velocity of cumulative big dispersed phase, flow velocity when by dispersed phase just with pattern across micropore membrane tube are set as maximum flow rate, then
The dispersed phase flow rates for measuring the micropore membrane tube in this aperture are critical flow velocity between maximum flow rate；
Dispersion is added in dispersed phase feeding equipment, dispersed phase fluid reservoir and dispersed phase cavity, air bleeding valve is opened, will be divided
It dissipates air in chamber to be discharged, gelatin solution is made to be full of cavity.Continuous phase fluid reservoir is added in paraffin oil, opens high flux membrane emulsification dress
Peristaltic pump in setting, makes continuous phase circulate.Dispersed phase feeding equipment is fixed on constant flow pump, the dispersion of constant flow pump is set
Phase flow velocity is 30mL/h, feed volume 15mL, and selection starts to feed, and what dispersed phase was stablized presses through microporous barrier pipe device, is connected
Continuous phase is taken away, and gelatin emulsion is obtained.Then, by lotion, stirring makes gelatine microsphere cure in 2 hours in ice-water bath (0 DEG C), uses
Acetone centrifuge washing removes paraffin oil three times, then through isopropanol centrifuge washing, and freeze-drying obtains gelatine microsphere.
Embodiment 6：
The present embodiment provides a kind of emulsification methods preparing W/O/W types using the membrane emulsifier.By the PLGA (n of 2.0gLA:
nGA=70:30, Mw=10,0000) it is dissolved in 40mL dichloromethane, as oil phase；Using 5mL ultra-pure waters as inner aqueous phase；It will be oily
It is mutually mixed with inner aqueous phase, ultrasound 240 seconds under 500 watts of power.2.0g PVA are dissolved in ultra-pure water, as outer aqueous phase.
10 μm of micropore membrane tubes of selected hydrophily set lower flow parameters, observation point after 10 μm of micropore membrane tubes of hydrophily install
For dephasing across the state of micropore membrane tube, flow velocity when dispersed phase be able to be stablized across micropore membrane tube is set as critical flow velocity；Gradually
Increase the flow velocity of dispersed phase, flow velocity when by dispersed phase just with pattern across micropore membrane tube is set as maximum flow rate, then surveys
The dispersed phase flow rates of the micropore membrane tube in this fixed aperture are critical flow velocity between maximum flow rate；
Miniemulsion is added in dispersed phase feeding equipment, dispersed phase fluid reservoir and dispersed phase cavity, air bleeding valve is opened, will be divided
It dissipates air in chamber to be discharged, dispersed phase is made to be full of cavity.Continuous phase fluid reservoir is added in PVA aqueous solutions, setting magnetic stirring apparatus turns
Speed is 150rpm, and dispersed phase feeding equipment is fixed on constant flow pump, and the dispersed phase flow velocity that constant flow pump is arranged is 30mL/h, charging
Volume is 15mL, and selection starts to feed, and what miniemulsion was stablized presses through micropore film device, is taken away by outer aqueous phase, obtains W/O/W type breasts
Liquid.Then, lotion is stirred at room temperature and removes organic solvent dichloromethane for 24 hours, then through centrifuge washing, freeze-drying obtains
PLGA micro-capsules.
Comparative example：
Select identical dispersed phase and continuous phase with embodiment 4, unlike using gas pressure control dispersed phase across
Micropore membrane tube.Concrete operations are as follows：After 2 μm of micropore membrane tubes of hydrophily install, by dispersion be added to dispersed phase storage tank and
In dispersed phase cavity, air bleeding valve is opened, air in dispersion chamber is discharged, PLGA solution is made to be full of cavity.Then, nitrogen is opened
Bottle, slowly increases pressure, and when lotion generates, top out pressure, and pressure is 30kPa at this time, and dispersed phase is under gas pressure
Micropore membrane tube is pressed through, is taken away by continuous phase, forms PLGA lotions, but with the reduction of dispersed phase, pressure continuously decreases, is needed at any time
It adjusts pressure and keeps pressure almost constant.The microscope photo such as the A in Fig. 4 of PLGA drops1、A2It is shown.At room temperature by lotion
Stirring removes organic solvent dichloromethane for 24 hours, then through centrifuge washing, and freeze-drying obtains PLGA microballoons, the scanning electricity of microballoon
B in mirror photo such as Fig. 41、B2It is shown.
From figure 3, it can be seen that the drop and microsphere average grain diameter that are obtained by the film emulsifying systems of voltage-stabilizing controller divide
Wei not be 35.7 ± 5.6 μm and 25.3 ± 3.9 μm, microspherulite diameter distribution is more uniform, does not find the presence of larger microballoon.And from figure
As can be seen that drop and microsphere average grain diameter that the film emulsifying systems controlled by gas pressure obtain are respectively 30.8 ± 7.1 in 4
μm and 23.35 ± 4.4 μm, but with the presence of the microballoon of greater particle size, maximum microspherulite diameter is 64.6 μm.
Claims (14)
1. a kind of membrane emulsifier, which is characterized in that including stablizing to pressure device and film emulsifier unit, film emulsifier unit includes conventional
Film emulsifier unit and high flux membrane emulsifier unit, conventional film emulsifier unit and high flux membrane emulsifier unit respectively by double valve with
Stablize and connected to pressure device, stablize and be set to controller for liquid flow to press fitting, it includes flowmeter, dispersed phase to stablize to pressure device
Feeding equipment and constant flow pump.
2. membrane emulsifier according to claim 1, which is characterized in that the flow is calculated as fluid flowmeter, the constant current
Pump is syringe pump or peristaltic pump.
3. membrane emulsifier according to claim 2, which is characterized in that fluid flow is calculated as differential pressure flowmeter, electromagnetic current
One kind in gauge, mass flowmenter.
4. membrane emulsifier according to claim 2, which is characterized in that syringe pump is that single channel syringe pump or multichannel are injected
Pump.
5. membrane emulsifier according to claim 2, which is characterized in that the dispersed phase feeding equipment includes syringe, note
Emitter one end is connected with syringe pump, and the syringe other end is connected with flowmeter；Or the dispersed phase feeding equipment includes beaker, is burnt
Cup is connected by peristaltic pump with flowmeter.
6. membrane emulsifier according to claim 1, which is characterized in that the maximum flow rate of constant flow pump ranging from 10 μ L/min-
43.35mL/min。
7. membrane emulsifier according to claim 6, which is characterized in that the volume range of dispersed phase feeding equipment is 1-
200mL。
8. membrane emulsifier according to claim 1, which is characterized in that film emulsifier unit includes dispersed phase fluid reservoir, film group
Part, continuous phase fluid reservoir and continuous phase flow device, membrane module include micropore membrane tube and dispersed phase cavity；
Conventional film emulsifier unit includes the first dispersed phase fluid reservoir, the first membrane module, the first continuous phase fluid reservoir, continuous phase flowing
Device；First membrane module includes the first micropore membrane tube and the first dispersed phase cavity, and the first dispersed phase cavity is by first
The plate washer of micropore membrane tube upper and lower ends is tightly connected to form the first dispersion with the housing liquid being enclosed in outside the first micropore membrane tube
Phase cavity, the first dispersed phase cavity are equipped with dispersed phase entrance and air bleeding valve, and dispersed phase entrance passes through stainless steel screw thread and sealing ring
It is connected to the discharge port of the first dispersed phase fluid reservoir；
High flux membrane emulsifier unit, including the second dispersed phase fluid reservoir, the second membrane module, the second continuous phase fluid reservoir, continuous phase
Flow device, the second membrane module include the second micropore membrane tube and the second dispersed phase cavity, and the second dispersed phase cavity is equipped with dispersed phase
Entrance and air bleeding valve, the second dispersed phase cavity further include that the continuous phase at both ends goes out muzzle, continuous phase import into muzzle, continuous phase
Set, continuous phase go out muzzle and are connect by stainless steel screw thread and sealing ring with the second dispersed phase cavity.
9. membrane emulsifier according to claim 8, which is characterized in that continuous phase flow device is magnetic stirring apparatus or drive
The pump of continuous phase flowing.
10. membrane emulsifier according to claim 9, which is characterized in that pump as peristaltic pump or electromagnetic pump.
11. membrane emulsifier according to claim 8, which is characterized in that the first micropore membrane tube, the second micropore membrane tube are equal
For hydrophily membrane tube or hydrophobicity membrane tube, including it is SPG films, ceramic membrane, metal film, polymeric membrane and microporous barrier molecular sieve,
The first micropore membrane tube, the second micropore membrane tube aperture include 2 μm, 5 μm, 10 μm, 20 μm, 50 μm.
12. membrane emulsifier according to claim 8, which is characterized in that the inside of the dispersed phase fluid reservoir is taper
Cavity or cylindrical cavity, inner surface are smooth surface, and dispersed phase fluid reservoir is dispersed phase fluid reservoir prepared by stainless steel, dispersion
It is equipped with upper capping above phase fluid reservoir, sealing ring is equipped between upper capping and dispersed phase fluid reservoir, upper capping is equipped with aperture, on
Capping is connected by aperture with the stable outlet to pressure device, and the tank mouth of dispersed phase fluid reservoir is quick coupling with upper capping.
13. membrane emulsifier according to claim 8, which is characterized in that the second continuous phase fluid reservoir includes to
The continuous phase return duct that two micropore membrane tubes are sent into the continuous phase feed pipe of continuous phase and continuous phase flows back.
14. a kind of emulsion preparation method using the membrane emulsifier as described in claim 1-13 any one claims, packet
Include following steps：
(1) the dispersed phase flow rates of different pore size micropore membrane tube are measured：The micropore membrane tube in a certain aperture is selected, it is to be installed good
Afterwards, lower flow parameters are set, observation dispersed phase be able to stablize dispersed phase across microporous barrier across the state of micropore membrane tube
Flow velocity when pipe is set as critical flow velocity；The flow velocity for gradually increasing dispersed phase, by dispersed phase just with pattern across microporous barrier
Flow velocity when pipe is set as maximum flow rate, then measures the dispersed phase flow rates of the micropore membrane tube in this aperture as critical flow velocity to maximum
Between flow velocity；
(2) lotion of uniform particle sizes is prepared：After micropore membrane tube installs, dispersed phase is filled it up with into dispersion feeding equipment, dispersed phase
In fluid reservoir and dispersed phase cavity, continuously will be added to continuous phase fluid reservoir, be arranged magnetic stirring apparatus magnetic stirring speed or
The pump for driving continuous phase flowing is opened, setting is stablized to the dispersed phase flow parameters of constant flow pump in pressure device, and the parameter is made to be located at
In dispersed phase flow rates in step (1), dispersed phase enters continuous phase with stable state across micropore membrane tube, obtains drop grain
The lotion that diameter is evenly distributed.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610495156.0A CN106139943B (en) | 2016-06-28 | 2016-06-28 | A kind of membrane emulsifier and emulsion preparation method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610495156.0A CN106139943B (en) | 2016-06-28 | 2016-06-28 | A kind of membrane emulsifier and emulsion preparation method |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN106139943A CN106139943A (en) | 2016-11-23 |
| CN106139943B true CN106139943B (en) | 2018-10-12 |
Family
ID=57350447
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610495156.0A Active CN106139943B (en) | 2016-06-28 | 2016-06-28 | A kind of membrane emulsifier and emulsion preparation method |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106139943B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110508223B (en) * | 2019-08-09 | 2022-07-12 | 百剂博递医药科技(上海)有限公司 | Preparation method and preparation mechanism of embryo microsphere, and preparation method and preparation device of microsphere |
| CN113875968A (en) * | 2020-07-03 | 2022-01-04 | 广州中国科学院先进技术研究所 | Preparation method of oil-soluble plant extract emulsion |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8910372D0 (en) * | 1989-05-05 | 1989-06-21 | Framo Dev Ltd | Multiphase process mixing and measuring system |
| JP4472234B2 (en) * | 2002-06-12 | 2010-06-02 | 大日本スクリーン製造株式会社 | Substrate processing apparatus and inert gas concentration control method |
| CN101683592B (en) * | 2008-09-28 | 2011-12-14 | 中国科学院过程工程研究所 | Membrane emulsifier and method of preparing emulsion |
| CN201930730U (en) * | 2011-01-07 | 2011-08-17 | 厦门市壳聚糖生物科技有限公司 | Membrane emulsifier |
| CN205760697U (en) * | 2016-06-28 | 2016-12-07 | 山东省科学院能源研究所 | A kind of membrane emulsifier |
-
2016
- 2016-06-28 CN CN201610495156.0A patent/CN106139943B/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN106139943A (en) | 2016-11-23 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN205760697U (en) | A kind of membrane emulsifier | |
| US10300409B2 (en) | High-density fine bubble-containing liquid producing method and high-density fine bubble-containing liquid producing apparatus | |
| CN106139943B (en) | A kind of membrane emulsifier and emulsion preparation method | |
| Joseph et al. | Evaluation of Shirasu Porous Glass (SPG) membrane emulsification for the preparation of colloidal lipid drug carrier dispersions | |
| Wu et al. | Multiplex coaxial flow focusing for producing multicompartment Janus microcapsules with tunable material compositions and structural characteristics | |
| CN109092178A (en) | A method of it preparing monodisperse and consolidates-compound the milk particle of water-oil | |
| Vladisavljević et al. | Production of food-grade multiple emulsions with high encapsulation yield using oscillating membrane emulsification | |
| Schneider et al. | Effects of chemical and physical parameters in the generation of microspheres by hydrodynamic flow focusing | |
| US11826311B2 (en) | Coaxial nozzle configuration and methods thereof | |
| CN108993334A (en) | A kind of preparation facilities and method of microballoon | |
| CN109569344B (en) | Method for preparing suspended micro-droplets by using micro-fluidic device | |
| CN113773521B (en) | Method for preparing emulsion and polymer particles with size less than 10 nanometers based on droplet self-breaking phenomenon | |
| WO2015072461A1 (en) | Microbicidal liquid-generating device | |
| CN110743634A (en) | Micro-fluidic device | |
| US20220287982A1 (en) | Embryonic microsphere preparation method and preparation mechanism, microsphere preparation method and preparation apparatus | |
| US10287404B2 (en) | Polymer particle, manufacturing method thereof, and separator for battery comprising the same | |
| CN107573523B (en) | A kind of eccentric structure polymer microballoon and preparation method thereof | |
| CN116273220A (en) | Interface infiltration endocytic emulsification microfluidic method for controllably preparing monodisperse double emulsion | |
| CN103111208B (en) | A kind of solid suspension list distribution emulsion and emulsification method thereof | |
| CN102553502A (en) | Preparation device and preparation method for electronic ink microcapsule | |
| CN206342710U (en) | A kind of liposome preparation system of continuous-stable | |
| CN203972184U (en) | The constant-pressure spraying device stirring | |
| CN202983712U (en) | Controllable constant-speed solution adding device | |
| US10173192B2 (en) | Quad-centric nozzle and system for hydrocapsule encapsulation | |
| JP2006272132A (en) | Method and apparatus for manufacture of chemical substance |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20200928 Address after: Room 509, building 1, 322 Shunfeng Road, Jinan area, China (Shandong) pilot Free Trade Zone, Jinan City, Shandong Province Patentee after: Shandong Mining Medical Technology Co.,Ltd. Address before: 250014 Shandong Province, Lixia District, Ji'nan City Hospital Road, No. 19 Patentee before: ENERGY Research Institute OF SHANDONG ACADEMY OF SCIENCES |