CN106139943A - A kind of membrane emulsifier and emulsion preparation method - Google Patents
A kind of membrane emulsifier and emulsion preparation method Download PDFInfo
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- CN106139943A CN106139943A CN201610495156.0A CN201610495156A CN106139943A CN 106139943 A CN106139943 A CN 106139943A CN 201610495156 A CN201610495156 A CN 201610495156A CN 106139943 A CN106139943 A CN 106139943A
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- 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
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- 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
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- 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
The present invention provides a kind of membrane emulsifier and emulsion preparation method, relate to film emulsification field, device includes: stable 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 connected to pressure device with stable by double valve respectively, stablize and be set to controller for liquid flow to press-fiting, stablize and include flowmeter, dispersion phase feed arrangement and constant flow pump to pressure device.The control of present invention fluid flow replaces the gas pressure control of existing membrane emulsifier, it is to avoid the use of nitrogen cylinder, simplifies equipment part, facilitates operation and the transport of instrument；Realize the accuracy controlling of transmembrane pressure, improve the stability of transmembrane pressure, it is ensured that the uniform particle diameter of drop and batch repeatability; it is beneficial to carry out standardizing and large-scale production; preparation process mild condition, can be used for the embedding etc. of bioactivator or labile drug, applied widely.
Description
Technical field
The present invention provides a kind of pressure to be accurately controlled, pressure stability, membrane emulsifier easy and simple to handle and emulsion preparation side
Method, relates 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.At present, typically use
Mechanical agitation, homogeneous and the method such as ultrasonic prepare emulsion and microballoon, although process conditions are simple, but uniform particle diameter difference, grain
Footpath size is difficult to control to, experimental repeatability difference.
In order to prepare emulsion and the nano-microspheres product of uniform particle diameter, film emulsifying technology developed rapidly in recent years.This technology exists
Can not only control the particle size of emulsion in preparation process, and particle diameter distribution is homogeneous, mild condition and energy consumption are 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 film emulsifier, and its operating procedure is: first by microporous barrier
Pipe installs, and then adds in fluid reservoir by dispersion phase, the pipeline above connection fluid reservoir and nitrogen cylinder, and keeps whole gas circuit
Airtight without leakage, regulate continuous phase stir speed (S.S.), open nitrogen pressure valve, slowly rise high pressure, when emulsion generates, this pressure is
For critical pressure, keep this pressure that by fenestra, dispersion phase is pressed into outer aqueous phase and form emulsion droplets, in the process, it is necessary to tight
Lattice keep the stability of nitrogen pressure.Because the size of mould the particle diameter of emulsion droplets, particle diameter are distributed and formed have important
Impact.Cause dispersion phase to be injected into continuous phase if mould crosses conference, form the emulsion droplets of big particle diameter；If mould mistake
Little meeting causes film emulsion process overlong time, affects production efficiency.And, with the carrying out of emulsification, the reduction of dispersion phase liquid level
The fluctuation of pressure can be caused.Meanwhile, pressurization, the control of release equal pressure of emulsifier is manual operation, is also easily caused pressure not
Stable.Meanwhile, when utilizing membrane emulsifier to prepare big particle diameter microballoon, the pressure of needs is very low, steady to manometric precision and pressure
Qualitative requirement is higher, has very big challenge to device operator.
Chinese patent document 200810223283.0 (notification number CN101683592) discloses a kind of membrane emulsifier, including
Membrane module, dispersion phase head tank, voltage stabilizing pay-off and continuous phase head tank；The voltage stabilizing pay-off that this invention provides achieves
Emulsion high-caliber batch repeatability, effectively increases the quality of emulsion, but the pressure device of giving of this membrane emulsifier still uses gas
To pressure mode, pressure transient, although improve pressure stability with voltage stabilizing pay-off, but voltage stabilizing pay-off is generally external
Inlet device, price costly, adds the cost of instrument, it is difficult to realize industrialization.
The major defect of prior art is that dispersion phase transmembrane pressure derives from gas pressure, and being adjusted to of its size is manually grasped
Making, the precision and stability of pressure is difficult to control to, so that the particle diameter of microballoon and the repeated experience by device operator of batch
Affect bigger, it is difficult to carry out standardizing and large-scale production.Accordingly, it is desirable to provide a kind of pressure can accuracy controlling, pressure stability,
Easy and simple to handle, be beneficial to carry out the new membrane emulsifier of industrialized production.
Content of the invention
The purpose of the present invention solves shortcoming of the prior art exactly, provide a kind of pressure can accuracy controlling, pressure stability,
Easy and simple to handle, be beneficial to carry out membrane emulsifier and the emulsification method of industrialized production.
Technical scheme is as follows:
In order to solve the problems referred to above, the present invention provides a kind of membrane emulsifier, replaces the emulsification of existing film with fluid flow control
The gas pressure control of device, it is achieved the accuracy controlling of pressure simultaneously improves pressure stability.
A kind of membrane emulsifier, including stable to pressure device and film emulsifier unit, film emulsifier unit includes conventional film emulsification dress
Putting and high flux membrane emulsifier unit, conventional film emulsifier unit and high flux membrane emulsifier unit give pressure by double valve with stable respectively
Device connects, and stablizes and is set to controller for liquid flow to press-fiting, and stablizes and includes flowmeter, dispersion phase feed arrangement to pressure device
And constant flow pump.
According to currently preferred, described flow is calculated as fluid flowmeter, and fluid flow is calculated as differential pressure flowmeter, electromagnetism
One in flowmeter, mass flowmenter, described constant flow pump is for can the syringe pump of accuracy controlling flow velocity or peristaltic pump.
It is further preferred that described dispersion phase feed arrangement includes syringe, syringe one end is connected with syringe pump, injection
The device other end is connected with flowmeter；Or described dispersion phase feed arrangement includes beaker, beaker is connected with flowmeter by peristaltic pump.
It is further preferred that described syringe pump is single channel syringe pump or multichannel injection pump.
It is further preferred that the Peak Flow Rate of described constant flow pump selects according to the aperture of micropore membrane tube, Peak Flow Rate scope
It is 10 μ L/min-43.35mL/min.
It is further preferred that depending on the volume of described dispersion phase feed arrangement is because of different experiments needs, range is 1-
200mL。
According to currently preferred, film emulsifier unit includes dispersion phase fluid reservoir, membrane module, continuous phase fluid reservoir and continuously
Phase flow device, membrane module includes micropore membrane tube and dispersion phase cavity；
Conventional film emulsifier unit includes the first dispersion phase fluid reservoir, the first membrane module, the first continuous phase fluid reservoir, continuous phase
Flow device；Described first membrane module includes the first micropore membrane tube and the first dispersion phase cavity, described first dispersion phase cavity by
The plate washer at the first upper and lower two ends of micropore membrane tube is tightly connected formation first with the overcoat liquid being enclosed in outside described first micropore membrane tube
Dispersion phase cavity, the first dispersion phase cavity is provided with dispersion phase entrance and air bleeding valve, and dispersion phase entrance passes through stainless steel screw thread and close
Seal connects with the discharging opening of the first dispersion phase fluid reservoir；
High flux membrane emulsifier unit, including the second dispersion phase fluid reservoir, the second membrane module, the second continuous phase fluid reservoir, company
Continuous phase flow device, the second membrane module includes the second micropore membrane tube and the second dispersion phase cavity, and the second dispersion phase cavity is provided with point
Dephasing entrance and air bleeding valve, the second dispersion phase cavity is additionally included in that the continuous phase at two ends enters muzzle, continuous phase goes out muzzle, continuous phase
Enter muzzle, continuous phase goes out muzzle and the second dispersion phase cavity is all connected by stainless steel screw thread and sealing ring.
It is further preferred that continuous phase flow device is magnetic stirring apparatus or the pump driving continuous phase flowing, pump is for wriggling
Pump or electromagnetic pump.
It is further preferred that described first micropore membrane tube, the second micropore membrane tube are hydrophily membrane tube or hydrophobicity membrane tube,
Owing to membrane tube material is different, including for SPG (Shirasu Porous Glass) film, ceramic membrane, metal film, polymeric membrane and
Microporous barrier molecular sieve, described first micropore membrane tube, the aperture of the second micropore membrane tube include 2 μm, 5 μm, 10 μm, 20 μm, 50 μm.
It is further preferred that the inside of described dispersion phase fluid reservoir is conical cavity or cylindrical cavity, inner surface is
Smooth surface, dispersion phase fluid reservoir is dispersion phase fluid reservoir prepared by stainless steel, and dispersion phase fluid reservoir is arranged over upper cover, on
Being provided with sealing ring between capping and dispersion phase fluid reservoir, to ensure to seal without leakage, upper cover is provided with aperture, and upper cover passes through little
Hole is connected to the outlet of pressure device with stable, and the tank mouth of dispersion phase fluid reservoir and upper cover are snap joint, it is ensured that sealing, easily
Operation.
It is further preferred that the second described continuous phase fluid reservoir includes sending into the continuous of continuous phase to the second micropore membrane tube
Phase feed pipe and the continuous phase return duct by continuous phase backflow.
The present invention also provides a kind of method utilizing above-mentioned membrane emulsifier to prepare emulsion, comprises the steps:
(1) the dispersion phase flow rates of different pore size micropore membrane tube is measured: select the micropore membrane tube in a certain aperture, to be installed
After Hao, set relatively low flow parameters, observe dispersion phase and stride across the state of micropore membrane tube, dispersion phase be able to stably be striden across micropore
Flow velocity during membrane tube is set to critical flow velocity；It is gradually increased the flow velocity of dispersion phase, dispersion phase is striden across micropore with pattern just
Flow velocity during membrane tube is set to Peak Flow Rate, then the dispersion phase flow rates of the micropore membrane tube measuring this aperture is that critical flow velocity arrives
Between big flow velocity；
(2) prepare the emulsion of uniform particle sizes: after micropore membrane tube installs, dispersion phase is filled it up with dispersion feed arrangement, divides
In dephasing fluid reservoir and dispersion phase cavity, continuous phase is added continuous phase fluid reservoir, the magnetic agitation speed of magnetic stirring apparatus is set
Degree or the pump opening drive continuous phase flowing, arrange stable to the dispersion phase flow parameters of constant flow pump in pressure device, make this parameter
The dispersion phase flow rates being positioned in step (1), dispersion phase strides across micropore membrane tube with stable state and enters continuous phase, obtains liquid
Drip the emulsion of even particle size distribution.
The beneficial effects of the present invention is:
1st, the present invention is stable to pressure device by arranging, and replaces the gas pressure of existing membrane emulsifier with fluid flow control
Control, utilizes constant flow pump accurately to regulate dispersion phase flow velocity and accurately changes dispersion phase transmembrane pressure, it is achieved transmembrane pressure accurate
Regulation and control, improve the stability of transmembrane pressure, it is ensured that the uniform particle diameter of drop and batch repeatability.
2nd, the present invention provides through arrange flowermeter, in real time monitoring disperse phase flow state.Meanwhile, existing gas is given
Pressure device is usually nitrogen cylinder and pressure valve, conventional nitrogen bottle height 145cm, weight 50.5kg, takes up room big, be difficult to move and
Transport, and stablizing that the present invention provides sets high 10cm to press-fiting, weight 3.6kg, volume is little, simply light, simplifies film emulsifying device
Accessory, facilitates operation and the transport of instrument, is beneficial to carry out standardizing and large-scale production.
3rd, drop/Microsphere Size that prepared by the membrane emulsifier using the present invention to provide is homogeneous, size tunable, batch repeatability
Good, and preparation process mild condition, can be used for the embedding etc. of bioactivator or labile drug.The film that the present invention provides
Emulsifier is simple to operate, applied widely, can be used for all conventional emulsions or the microballoons such as preparation W/O/W type, O/W type and w/o type
Preparation system.
Brief description
Fig. 1 is the structural representation of inventive film emulsifier；
Fig. 2 a is that the embodiment of the present invention 1 membrane emulsifier is stable to the schematic diagram of pressure device；
Fig. 2 b is that the embodiment of the present invention 2 membrane emulsifier is stable 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
The microphotograph of emulsion droplet, B in Fig. 31、B2Microballoon stereoscan photograph for different enlargement ratios；
Fig. 4 is the microballoon result figure utilizing existing conventional film emulsifier to prepare in comparative example；A in Fig. 41、A2Amplify for difference
The microphotograph of the emulsion droplet of multiplying power, B in Fig. 41、B2Microballoon stereoscan photograph for different enlargement ratios；
Wherein: the 1st, stable to pressure device, the 2nd, upper cover, the 3rd, the first dispersion phase fluid reservoir, the 4th, conventional film emulsifier unit, the 5th, the
One continuous phase fluid reservoir, the 6th, the first dispersion phase cavity, the 7th, the first micropore membrane tube, the 8th, magneton, the 9th, magnetic stirring apparatus, the 10th, double valve,
11st, air bleeding valve, the 12nd, the second dispersion phase fluid reservoir, the 13rd, lower capping, the 14th, high flux membrane emulsifier unit, the 15th, the second dispersion phase chamber
Body, the 16th, the second micropore membrane tube, the 17th, continuous phase feed pipe, the 18th, continuous phase return duct, the 19th, the second continuous phase fluid reservoir, the 20th, compacted
Dynamic pump, the 21st, syringe, the 22nd, plate washer after syringe pump, the 23rd, syringe pump front baffle board, the 24th, syringe pump, the 25th, flowmeter, the 26th, beaker,
27th, peristaltic pump feed pipe, the 28th, peristaltic pump, the 29th, peristaltic pump discharge nozzle.
Detailed description of the invention
It below by embodiment and combine accompanying drawing the present invention will be further described, but is not limited to this.
Embodiment 1:
The present invention provides a kind of membrane emulsifier, as it is shown in figure 1, this equipment includes stable to pressure device the 1st, conventional film emulsification dress
Put 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 connect to pressure device 1, stablize and control to pressure device to pressure device 1 for fluid flow, stablize and include flow to pressure device 1
Meter, dispersion phase feed arrangement and constant flow pump.
Wherein, stable to pressure device 1 as shown in Figure 2 a, including the syringe pump being sequentially connected with the 24th, dispersion phase feed arrangement and
Flowmeter 25, syringe pump is single channel syringe pump, and flow is calculated as differential pressure flowmeter, and dispersion phase feed arrangement is syringe 21,
Pass through syringe pump front apron 23 between single channel syringe pump and syringe and syringe pump backboard 22 is fixed and is connected, flowmeter and note
Emitter connects, and monitors the actual flow velocity of dispersion phase in real time, it is ensured that the stability of disperse phase flow.
Film emulsifier unit includes dispersion phase fluid reservoir, membrane module, continuous phase fluid reservoir and continuous phase flow device, membrane module
Including micropore membrane tube and dispersion phase cavity；For distinguishing conventional film emulsifier unit and high flux membrane emulsifier unit, with first, secondth district
Divide name.
The 5th, conventional film emulsifier unit 4 includes the first dispersion phase fluid reservoir the 3rd, the first continuous phase fluid reservoir of from top to bottom connecting
First dispersion phase cavity the 6th, the first micropore membrane tube the 7th, continuous phase flow device, continuous phase flow device includes magnetic stirring apparatus 9 He
Magneton 8；First dispersion phase cavity by the plate washer at the first upper and lower two ends of micropore membrane tube be enclosed in outside described first micropore membrane tube
Overcoat liquid is tightly connected formation the first dispersion phase cavity, and the first dispersion phase cavity is provided with dispersion phase entrance and air bleeding valve 11, dispersion
Phase entrance is connected with the discharging opening of sealing ring and the first dispersion phase fluid reservoir by stainless steel screw thread, and air bleeding valve 11 adds in order to get rid of
The bubble producing during material.
The inside of the first dispersion phase fluid reservoir 3 is conical cavity, and inner surface is smooth surface, and the first dispersion phase fluid reservoir is
First dispersion phase fluid reservoir prepared by stainless steel, the first dispersion phase fluid reservoir 3 is arranged over upper cover 2, upper cover 2 and first point
Accompany sealing ring between dephasing fluid reservoir 3, use snap joint, it is ensured that sealing, easily operate.Upper cover 2 is provided with aperture, and surely
Fixed connected to the outlet of pressure device.
High flux membrane emulsifier unit 14 includes the second dispersion phase fluid reservoir the 12nd, the second dispersion phase cavity the 15th, second connecting
Micropore membrane tube the 16th, the second continuous phase fluid reservoir 19 and continuous phase flow device, continuous phase flow device is peristaltic pump 20.
Wherein, the second dispersion phase cavity 15 is provided with dispersion phase entrance and air bleeding valve 11, and air bleeding valve 11 fed in order to get rid of
The bubble producing in journey.Second dispersion phase fluid reservoir 12 is circular cylindrical cavity, including upper cover 2 and lower capping 13, upper cover 2 with
Between second dispersion phase fluid reservoir 12, lower capping 13 and second all accompany pad between dispersion phase fluid reservoir 12, use and quickly connect
Head connects.Upper cover 2 is provided with aperture, is connected to the outlet of pressure device with stable.Second dispersion phase cavity is additionally included in two ends
Continuous phase enters muzzle, continuous phase goes out muzzle, and continuous phase enters muzzle, continuous phase goes out muzzle and the second dispersion phase cavity is all by stainless
Steel screw thread and sealing ring connect.
Wherein, the second continuous phase fluid reservoir 19 also includes the continuous phase feed pipe 17 sending into continuous phase to the second micropore membrane tube
With the continuous phase return duct 18 that continuous phase is refluxed.
In addition, micropore membrane tube is hydrophily SPG membrane tube, described micropore membrane tube specification is: the first micropore membrane tube a length of
20mm, aperture is 2 μm, a length of 125mm of the second micropore membrane tube, and aperture is 2 μm.
Embodiment 2:
The present embodiment provides a kind of pressure stability, it is easy to the membrane emulsifier of operation, structure as described in Example 1, with it not
It is with part: stablize to pressure device 1 as shown in Figure 2 b, including the flowmeter being sequentially connected with the 25th, peristaltic pump 28 and dispersion phase enter
Material device, dispersion phase feed arrangement is beaker 26.The flow velocity of dispersion phase monitored in real time by flowmeter 25, it is ensured that disperse phase flow steady
Qualitative, peristaltic pump 28 by dispersion phase by dispersion phase feed arrangement through peristaltic pump feed pipe the 27th, peristaltic pump discharge nozzle 29 and flowmeter
The 25 dispersion phase fluid reservoirs being transported to film emulsifier unit.
Embodiment 3:
The present embodiment provides a kind of pressure stability, it is easy to the membrane emulsifier of operation, structure as described in Example 1, with it not
It is with part: syringe pump is multichannel injection pump.
Embodiment 4:
The present embodiment provides a kind of emulsification method utilizing this membrane emulsifier to prepare O/W type emulsion.By the PLGA of 2.0g
(nLA:nGA=70:30, Mw=10,0000) it is dissolved in 40mL dichloromethane, as dispersion phase (oil phase)；2.0g PVA is dissolved
In ultra-pure water, as continuous phase (aqueous phase).Selected 2 μm of micropore membrane tube of hydrophily, after hydrophily μm micropore membrane tube installs,
Set relatively low flow parameters, observe dispersion phase and stride across the state of micropore membrane tube, dispersion phase be able to stably be striden across micropore membrane tube
When flow velocity be set to critical flow velocity；It is gradually increased the flow velocity of dispersion phase, dispersion phase is striden across micropore membrane tube with pattern just
When flow velocity be set to Peak Flow Rate, then the dispersion phase flow rates of the micropore membrane tube measuring this aperture is that critical flow velocity arrives max-flow
Between Su；
PLGA solution is added dispersion phase feed arrangement, dispersion phase fluid reservoir and dispersion phase cavity, opens air bleeding valve, will divide
In dephasing cavity, air is discharged, and makes PLGA solution be full of dispersion phase cavity.Then, the PVA aqueous solution is added continuous phase fluid reservoir,
Arranging magnetic stirring apparatus rotating speed is 150rpm, is fixed on dispersion phase feed arrangement on constant flow pump, arranges the dispersion phase of constant flow pump
Flow velocity is 20mL/h, and feed volume is 8mL, selects to start charging, and what dispersion phase was stable presses through microporous barrier device, by continuous facies tract
Walk, obtain PLGA emulsion, the microphotograph of its drop such as the A in Fig. 31、A2Shown in.Then, emulsion is stirred at room temperature
24h removes organic solvent dichloromethane, then through centrifuge washing, freeze-drying obtains PLGA microballoon, and the ESEM of its microballoon shines
Piece such as the B in Fig. 31、B2Shown in.
Embodiment 5:
The present embodiment provides a kind of emulsification method utilizing this membrane emulsifier to prepare w/o type emulsion.By molten for the gelatin of 2.0g
In 18.0g ultra-pure water, heat 1 hour in 45 DEG C of water-baths, after gelatin is completely dissolved, as dispersion phase (aqueous phase)；Will
1.0g sorbitan fatty ester (Span80) is dissolved in the paraffin oil of 350mL, as continuous phase (oil after fully dissolving
Phase).Selected 5 μm of micropore membrane tube of hydrophobicity, after 5 μm of micropore membrane tube of hydrophobicity install, set relatively low flow parameters, observe
Dispersion phase strides across the state of micropore membrane tube, and flow velocity when dispersion phase be able to stably be striden across micropore membrane tube is set to critical flow velocity；By
The flow velocity of cumulative big dispersion phase, flow velocity when just dispersion phase is striden across micropore membrane tube with pattern is set to Peak Flow Rate, then
The dispersion phase flow rates of the micropore membrane tube measuring this aperture is critical flow velocity between Peak Flow Rate；
In dispersion phase is added dispersion phase feed arrangement, dispersion phase fluid reservoir and dispersion phase cavity, open air bleeding valve, will divide
Dissipate air in chamber to discharge, make gelatin solution be full of cavity.Paraffin oil is added continuous phase fluid reservoir, opens high flux membrane emulsification dress
Peristaltic pump in putting, makes continuous phase circulate.It is fixed on dispersion phase feed arrangement on constant flow pump, the dispersion of constant flow pump is set
Phase flow velocity is 30mL/h, and feed volume is 15mL, selects to start charging, and what dispersion phase was stable presses through micropore membrane tube device, connected
Continue and take away mutually, obtain gelatin emulsion.Then, by emulsion, in ice-water bath (0 DEG C), stirring makes gelatine microsphere cure for 2 hours, uses
Acetone centrifuge washing removes paraffin oil three times, then through isopropanol centrifuge washing, freeze-drying obtains gelatine microsphere.
Embodiment 6:
The present embodiment provides a kind of emulsification method utilizing this membrane emulsifier to prepare W/O/W type.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 water as interior aqueous phase；By oil
Mutually and the mixing of interior aqueous phase, under the power of 500 watts ultrasonic 240 seconds.It is dissolved in 2.0g PVA in ultra-pure water, as outer aqueous phase.
Selected 10 μm of micropore membrane tube of hydrophily, after 10 μm of micropore membrane tube of hydrophily install, set relatively low flow parameters, observe and divide
Dephasing strides across the state of micropore membrane tube, and flow velocity when dispersion phase be able to stably be striden across micropore membrane tube is set to critical flow velocity；Gradually
Increasing the flow velocity of dispersion phase, flow velocity when just dispersion phase is striden across micropore membrane tube with pattern is set to Peak Flow Rate, then surveys
The dispersion phase flow rates of the micropore membrane tube in this aperture fixed is critical flow velocity between Peak Flow Rate；
Add miniemulsion in dispersion phase feed arrangement, dispersion phase fluid reservoir and dispersion phase cavity, open air bleeding valve, will divide
Dissipate air in chamber to discharge, make dispersion phase be full of cavity.The PVA aqueous solution is added continuous phase fluid reservoir, magnetic stirring apparatus is set and turns
Speed is 150rpm, is fixed on dispersion phase feed arrangement on constant flow pump, and the dispersion phase flow velocity arranging constant flow pump is 30mL/h, charging
Volume is 15mL, selects to start charging, and what miniemulsion was stable presses through microporous barrier device, is taken away by outer aqueous phase, obtains W/O/W type breast
Liquid.Then, emulsion is stirred at room temperature 24h and removes organic solvent dichloromethane, then through centrifuge washing, freeze-drying obtains
PLGA micro-capsule.
Comparative example:
Select identical dispersion phase and continuous phase with embodiment 4, except for the difference that use gas pressure control dispersion phase to stride across
Micropore membrane tube.Concrete operations are as follows: after 2 μm of micropore membrane tube of hydrophily install, by dispersion phase add dispersion phase storage tank and
In dispersion phase cavity, open air bleeding valve, air in chamber will be disperseed to discharge, make PLGA solution be full of cavity.Then, nitrogen is opened
Bottle, slowly rises high pressure, and when emulsion generates, top out pressure, and now pressure is 30kPa, and dispersion phase is under gas pressure
Press through micropore membrane tube, taken away by continuous phase, form PLGA emulsion, but with the minimizing of dispersion phase, pressure is gradually lowered, need at any time
Regulation pressure keeps pressure almost constant.The microphotograph of PLGA drop such as the A in Fig. 41、A2Shown in.By emulsion at room temperature
Stirring 24h removes organic solvent dichloromethane, then through centrifuge washing, freeze-drying obtains PLGA microballoon, the scanning electricity of its microballoon
Mirror photo such as the B in Fig. 41、B2Shown in.
From figure 3, it can be seen that the drop and the microsphere average grain diameter that are obtained by the film emulsifying systems of voltage-stabilizing controller divide
Not being 35.7 ± 5.6 μm and 25.3 ± 3.9 μm, microspherulite diameter distribution is more uniform, does not finds the existence of bigger microballoon.And from figure
It can be seen that the drop that obtains of the film emulsifying systems being controlled by gas pressure and microsphere average grain diameter 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 (10)
1. a membrane emulsifier, it is characterised in that including stable to pressure device and film emulsifier unit, film emulsifier unit includes routine
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 connect to pressure device, stablize and be set to controller for liquid flow to press-fiting, stablize and include flowmeter, dispersion phase to pressure device
Feed arrangement and constant flow pump.
2. membrane emulsifier according to claim 1, it is characterised in that described flow is calculated as fluid flowmeter, fluid flow
Being calculated as differential pressure flowmeter, electromagnetic flowmeter, the one in mass flowmenter, described constant flow pump is syringe pump or peristaltic pump；Excellent
Choosing, syringe pump is single channel syringe pump or multichannel injection pump.
3. membrane emulsifier according to claim 2, it is characterised in that described dispersion phase feed arrangement includes syringe, note
Emitter one end is connected with syringe pump, and the syringe other end is connected with flowmeter；Or described dispersion phase feed arrangement includes beaker, burn
Cup is connected with flowmeter by peristaltic pump.
4. membrane emulsifier according to claim 1, it is characterised in that the Peak Flow Rate scope of constant flow pump is 10 μ L/min-
43.35mL/min；Preferably, the volume range of dispersion phase feed arrangement is 1-200mL.
5. membrane emulsifier according to claim 1, it is characterised in that film emulsifier unit includes dispersion phase fluid reservoir, film group
Part, continuous phase fluid reservoir and continuous phase flow device, membrane module includes micropore membrane tube and dispersion phase cavity；
Conventional film emulsifier unit includes the first dispersion phase fluid reservoir, the first membrane module, the first continuous phase fluid reservoir, continuous phase flowing
Device；Described first membrane module includes the first micropore membrane tube and the first dispersion phase cavity, and described first dispersion phase cavity is by first
The plate washer at the upper and lower two ends of micropore membrane tube and the overcoat liquid being enclosed in outside described first micropore membrane tube are tightly connected formation the first dispersion
Phase cavity, the first dispersion phase cavity is provided with dispersion phase entrance and air bleeding valve, and dispersion phase entrance passes through stainless steel screw thread and sealing ring
Connect with the discharging opening of the first dispersion phase fluid reservoir；
High flux membrane emulsifier unit, including the second dispersion phase fluid reservoir, the second membrane module, the second continuous phase fluid reservoir, continuous phase
Flow device, the second membrane module includes the second micropore membrane tube and the second dispersion phase cavity, and the second dispersion phase cavity is provided with dispersion phase
Entrance and air bleeding valve, the second dispersion phase cavity is additionally included in that the continuous phase at two ends enters muzzle, continuous phase goes out muzzle, continuous phase import
Set, continuous phase go out muzzle and the second dispersion phase cavity is all connected by stainless steel screw thread and sealing ring.
6. membrane emulsifier according to claim 5, it is characterised in that continuous phase flow device is magnetic stirring apparatus or drive
The pump of continuous phase flowing, pump is peristaltic pump or electromagnetic pump.
7. membrane emulsifier according to claim 5, it is characterised in that described first micropore membrane tube, the second micropore membrane tube are equal
For hydrophily membrane tube or hydrophobicity membrane tube, including for SPG film, ceramic membrane, metal film, polymeric membrane and microporous barrier molecular sieve,
Described first micropore membrane tube, the aperture of the second micropore membrane tube include 2 μm, 5 μm, 10 μm, 20 μm, 50 μm.
8. membrane emulsifier according to claim 5, it is characterised in that the inside of described dispersion phase fluid reservoir is that taper is empty
Chamber or cylindrical cavity, inner surface is smooth surface, and dispersion phase fluid reservoir is dispersion phase fluid reservoir prepared by stainless steel, dispersion phase
Fluid reservoir is arranged over upper cover, is provided with sealing ring between upper cover and dispersion phase fluid reservoir, and upper cover is provided with aperture, upper envelope
Lid is connected to the outlet of pressure device with stable by aperture, and the tank mouth of dispersion phase fluid reservoir and upper cover are snap joint.
9. membrane emulsifier according to claim 5, it is characterised in that the second described continuous phase fluid reservoir includes to second
Micropore membrane tube sends into continuous phase feed pipe and the continuous phase return duct by continuous phase backflow of continuous phase.
10. an emulsion preparation method for membrane emulsifier as described in claim 1-9 any one claim for the utilization, including
Following steps:
(1) the dispersion phase flow rates of different pore size micropore membrane tube is measured: select the micropore membrane tube in a certain aperture, to be installed good
After, set relatively low flow parameters, observe dispersion phase and stride across the state of micropore membrane tube, dispersion phase be able to stably be striden across microporous barrier
Flow velocity during pipe is set to critical flow velocity；It is gradually increased the flow velocity of dispersion phase, dispersion phase is striden across microporous barrier with pattern just
Flow velocity during pipe is set to Peak Flow Rate, then the dispersion phase flow rates of the micropore membrane tube measuring this aperture is that critical flow velocity arrives maximum
Between flow velocity；
(2) prepare the emulsion of uniform particle sizes: after micropore membrane tube installs, dispersion phase is filled it up with dispersion feed arrangement, dispersion phase
In fluid reservoir and dispersion phase cavity, by continuous phase add continuous phase fluid reservoir, arrange magnetic stirring apparatus magnetic agitation speed or
Open the pump driving continuous phase flowing, arrange stable to the dispersion phase flow parameters of constant flow pump in pressure device, make this parameter be positioned at
In dispersion phase flow rates in step (1), dispersion phase strides across micropore membrane tube with stable state and enters continuous phase, obtains drop grain
The emulsion that footpath is evenly distributed.
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Cited By (2)
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| CN110508223A (en) * | 2019-08-09 | 2019-11-29 | 柏迪发瑞(上海)医药科技有限公司 | Embryo's method for preparing microsphere and preparing mechanism, method for preparing microsphere and preparation facilities |
| 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 |
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