CN103962075A

CN103962075A - Preparation method of composite microcapsule with monodisperse capsule-in-capsule structure

Info

Publication number: CN103962075A
Application number: CN201410209858.9A
Authority: CN
Inventors: 牟川淋; 褚良银; 汪伟; 巨晓洁; 谢锐
Original assignee: Sichuan University
Current assignee: Sichuan University
Priority date: 2014-05-19
Filing date: 2014-05-19
Publication date: 2014-08-06
Anticipated expiration: 2034-05-19
Also published as: CN103962075B

Abstract

The invention provides a preparation method of a composite microcapsule with a monodisperse capsule-in-capsule structure, and belongs to the field of preparation of functional polymer microcapsules. The method comprises the following processing steps: (1) preparing a first type or a second type of five-phase quadruple emulsion by a capillary microfluid device; (2) standing the first type of five-phase quadruple emulsion at room temperature for at least 10min to ensure that a cross-linking reaction of reaction monomers and a cross-linking agent is carried out to obtain a composite microcapsule blank body, or irradiating the second type of five-phase quadruple emulsion with ultraviolet light at the temperature of 2-20 DEG C for 10min-25min, and then standing at room temperature for at least 10min to ensure that a cross-linking reaction of reaction monomers and a cross-linking agent or of reaction monomers is carried out through photo-initiation so as to obtain a composite microcapsule blank body; and (3) washing the composite microcapsule blank body so as to obtain the composite microcapsule with the monodisperse capsule-in-capsule structure. The method is simple in process, and the prepared composite microcapsule is uniform in size, good in stability and high in safety.

Description

A kind of preparation method of single composite microcapsule that disperses capsule packing structure

Technical field

The invention belongs to functional polymer micro-capsule preparation field, particularly a kind of preparation method of single composite microcapsule that disperses capsule packing structure.

Background technology

Micro-capsule can be kept apart the space in micro-capsule and outside micro-capsule by film forming matter, protects and control release thereby realize the material that its inside bag is carried.In micro-capsule, bag is loaded with less micro-capsule, is called the composite microcapsule with " capsule packing " structure.There is the composite microcapsule of " capsule packing " structure for individual layer micro-capsule, there is how brand-new function.In the composite microcapsule of " capsule packing " structure, can wrap simultaneously and carry different active materials and different not mixing mutually of active material, for example, in same composite microcapsule, encapsulate according to a certain percentage different types of medicine and not cross pollution.Meanwhile, this composite microcapsule can also be realized its inner design and control of wrapping the order of the active material release at diverse location of carrying, and can also serve as the carrier that small-molecule substance control discharges.Therefore design and composite microcapsule that preparation has " capsule packing " structure has very important significance.

The preparation method of the composite microcapsule with " capsule packing " structure of report is considerably less at present.One method is to use self assembly layer by layer and co-precipitation polymerization technique by combining, and preparation has the composite microcapsule of " capsule packing " structure and (sees O.Kreft, M.Prevot, H. , and G.B.Sukhorukov Angew.Chem.Int.Ed.2007,46,5605 – 5608).First the method utilizes coprecipitation to prepare calcium carbonate microspheres; Then by the last layer polyelectrolyte membrane of growing of self-assembly method layer by layer, form the core-shell microspheres of polyelectrolyte film bag calcium carbonate on calcium carbonate microspheres surface; Subsequently by coprecipitation at core-shell microspheres superficial growth one deck calcium carbonate, and remove and do not cover the calcium carbonate byproduct of above-mentioned core-shell microspheres outer surface, obtain the microballoon of calcium carbonate bag polyelectrolyte layer bag calcium carbonate; Again, by the method for self assembly layer by layer one deck polyelectrolyte membrane of growing, obtain the microballoon of polyelectrolyte layer bag calcium carbonate bag polyelectrolyte layer bag calcium carbonate on the microsphere surface of calcium carbonate bag polyelectrolyte layer bag calcium carbonate; Finally with solvent by dissolution of calcium carbonate, there is the polyelectrolyte composite microcapsule of " capsule packing " structure.The method has the following disadvantages: (1) step is many, operation is very loaded down with trivial details, needs to separate unwanted byproduct in preparation process; (2) size of the polyelectrolyte composite microcapsule of preparing and inner structural controllability are poor, cause the poor controllability of its reactivity worth or release performance; (3) polyelectrolyte membrane is to be combined into by electrostatic interaction, and this combination is stable not, and polyelectrolyte composite microcapsule is easily destroyed.

Another kind method is that the composite microcapsule that has " capsule packing " structure by the method preparation of emulsification repeatedly in capillary microfluidic device (is shown in S.H.Kim, H.C.Shum, J.W.Kim, J.C.Cho, and D.A.Weitz J.Am.Chem.Soc.2011,133,15165 – 15171).The method is first by preparing the double emulsion of W/O/W in conjunction with micro-fluidic emulsion process, the amphipathic macromolecular self-assembly that is arranged in oil phase after solvent evaporates forms unitunicate polymeric acceptor micro-capsule; Then unitunicate polymeric acceptor micro-capsule being dispersed in the aqueous solution to perfusion enters and in micro fluidic device, carries out emulsification, again pass through solvent evaporates, again form one layer of polymeric micro-capsule outward at single polymer layer body micro-capsule, there is the polymeric acceptor composite microcapsule of " capsule packing " structure.But the method has the following disadvantages: (1) is used the method to prepare in the process of composite microcapsule, must use the poisonous and hazardous organic reagents such as chloroform and n-hexane; (2) the method is only applicable to prepare the molecular polymeric acceptor composite microcapsule of amphipathic high score, but due to chemical reaction not occurring between amphipathic macromolecule, just form polymeric acceptor composite microcapsule by hydrophilic and hydrophobic effect self assembly, so the poor stability of this composite microcapsule, or the destruction that too small in the situation that all can cause composite microcapsule excessive at extraneous osmotic pressure; (3) the method is only applicable to adopt the molten and water-insoluble amphipathic macromolecule of oil to prepare polymeric acceptor composite microcapsule, but the kind of this amphipathy macromolecule is limited, thereby the scope of application of the method is restricted; (4) the method must operate by substep in the process of preparing composite microcapsule, and this can cause the monodispersity of composite microcapsule to reduce, and its loaded down with trivial details preparation process is also unfavorable for the scale preparation in batches of composite microcapsule.

Summary of the invention

The deficiency existing for prior art, the object of the present invention is to provide a kind of preparation method of single composite microcapsule that disperses capsule packing structure, and the technique of the method is simple, and the composite microcapsule size homogeneous of preparation, good stability, security are higher.

The preparation method of single composite microcapsule that disperses capsule packing structure of the present invention, processing step is as follows:

(1) prepare five phase quadruple emulsions

1. prepare the first kind five phase quadruple emulsions

Interior oil phase, interior water, middle oil phase, outer water, outer oil phase are injected respectively to injection-tube, First Transition pipe, the second transition conduit, the 3rd transition conduit and the collecting pipe of capillary microfluidic device by syringe, form monodispersed interior oil phase/interior water/middle oil phase/outer water/outer oil phase five phase quadruple solution, then this five phases quadruple emulsion is introduced in collection oil phase by exporting with capillary microfluidic device collecting pipe the pipe fitting being connected; In described interior water and outer water, contain reaction monomers but do not contain crosslinking agent, in two oil phases adjacent with interior water not containing reaction monomers but at least one oil phase contains crosslinking agent, in two oil phases adjacent with outer water not containing reaction monomers but at least one oil phase contains crosslinking agent;

Or 2. prepare Equations of The Second Kind five phase quadruple emulsions

Interior oil phase, interior water, middle oil phase, outer water, outer oil phase are injected respectively to injection-tube, First Transition pipe, the second transition conduit, the 3rd transition conduit and the collecting pipe of capillary microfluidic device under lucifuge condition by syringe, form monodispersed interior oil phase/interior water/middle oil phase/outer water/outer oil phase five phase quadruple solution, then this five phases quadruple emulsion is introduced in collection oil phase by exporting with capillary microfluidic device collecting pipe the pipe fitting being connected;

In described interior water, contain reaction monomers, crosslinking agent, light trigger or contain reaction monomers, light trigger, in outer water, contain reaction monomers, crosslinking agent, light trigger or contain reaction monomers, light trigger, two oil phases adjacent with interior water neutralize in two oil phases adjacent with outer water containing reaction monomers and crosslinking agent; In order to promote the cross-linking reaction of reaction monomers and crosslinking agent or reaction monomers and reaction monomers, in the adjacent oil phase of interior water and outer water, can also contain light trigger;

Or in described interior water, contain reaction monomers, crosslinking agent, light trigger or contain reaction monomers, light trigger, in two oil phases adjacent with interior water, do not contain reaction monomers, in outer water, contain reaction monomers but not containing crosslinking agent and light trigger, in two oil phases adjacent with outer water, do not contain reaction monomers but contain crosslinking agent at least one oil phase; In order to promote the cross-linking reaction of reaction monomers and crosslinking agent or reaction monomers and reaction monomers, in the adjacent oil phase of interior water, can also contain light trigger;

Or in described outer water, contain reaction monomers, crosslinking agent, light trigger or contain reaction monomers, light trigger, in two oil phases adjacent with outer water, do not contain reaction monomers, in interior water, contain reaction monomers but not containing crosslinking agent and light trigger, in two oil phases adjacent with interior water, do not contain reaction monomers but contain crosslinking agent at least one oil phase; In order to promote the cross-linking reaction of reaction monomers and crosslinking agent or reaction monomers and reaction monomers, in the adjacent oil phase of outer water, can also contain light trigger;

Two oil phases that described and interior water is adjacent are interior oil phase and middle oil phase, and two oil phases that described and outer water is adjacent are oil phase and the middle oil phase forming after outer oil phase mixes with collection oil phase;

(2) prepare composite microcapsule base substrate

The first kind five phase quadruple emulsions are left standstill at least 10min in room temperature, make reaction monomers and crosslinking agent generation cross-linking reaction obtain composite microcapsule base substrate; Or by Equations of The Second Kind five phase quadruple emulsions at 2～20 DEG C with UV-irradiation 10～25min, then leave standstill at least 10min in room temperature, make reaction monomers and crosslinking agent or reaction monomers and reaction monomers obtain composite microcapsule base substrate by light-initiated generation cross-linking reaction;

(3) washing

With cleaning solvent washing composite microcapsule base substrate to remove in composite microcapsule and micro-capsule oil phase around, then with deionized water wash away remain on composite microcapsule wall and micro-capsule in cleaning solvent, obtain single composite microcapsule that disperses capsule packing structure; Or soak composite microcapsule base substrate to remove the oil phase on composite microcapsule outer wall by deionized water, obtain single composite microcapsule that disperses capsule packing structure.

In said method, in the time in step (2) being reaction monomers and crosslinking agent generation cross-linking reaction formation composite microcapsule, being combined as water soluble chitosan and terephthalaldehyde or being NIPA and N, N-methylene-bisacrylamide of the reaction monomers adopting and crosslinking agent; In the time in step (2) being reaction monomers and reaction monomers generation cross-linking reaction formation composite microcapsule, the reaction monomers adopting is polyethyleneglycol diacrylate.

In said method, described interior water or outer water are the one in the first water, the second water, the 3rd water, and the compound method of the first water, the second water, the 3rd water is as follows:

The first water: water soluble chitosan, water soluble emulsifier, water-soluble thickener are added in deionized water in room temperature, stirring makes water soluble chitosan, water soluble emulsifier, water-soluble thickener dissolve formation mixed liquor completely, then regulates pH value to 6.3～6.7 of described mixed liquor with sodium hydrate aqueous solution; The mass ratio of described water soluble chitosan and deionized water is (0.02～0.06): 1, the mass ratio of water soluble emulsifier and deionized water is (0.0025～0.02): 1, and the mass ratio of water-soluble thickener and deionized water is (0.01～0.02): 1;

The second water: under room temperature, lucifuge condition by NIPA, N, N-methylene-bisacrylamide, water soluble emulsifier, water-soluble light trigger add in deionized water, stirring makes NIPA, N, and N-methylene-bisacrylamide, water soluble emulsifier, water-soluble light trigger dissolve completely; The mass ratio of described NIPA and deionized water is (0.1～0.13): 1, N, the mass ratio of N-methylene-bisacrylamide and deionized water is (0.006～0.01): 1, the mass ratio of water soluble emulsifier and deionized water is (0.0025～0.02): 1, and the mass ratio of water-soluble light trigger and deionized water is (0.003～0.02): 1;

The 3rd water: under room temperature, lucifuge condition, polyethyleneglycol diacrylate, water soluble emulsifier, water-soluble light trigger are added in deionized water, stir polyethyleneglycol diacrylate, water soluble emulsifier, water-soluble light trigger are dissolved completely; The mass ratio of described polyethyleneglycol diacrylate and deionized water is (0.06～0.2): 1, the mass ratio of water soluble emulsifier and deionized water is (0.0025～0.02): 1, and the mass ratio of water-soluble light trigger and deionized water is (0.003～0.02): 1;

Described water soluble emulsifier is Pluronic F127, Pluronic F108, Pluronic F68 or Pluronic F188, described water-soluble thickener is hydroxyethylcellulose, and described water-soluble light trigger is azo diisobutyl amidine hydrochloride, ammonium persulfate, potassium peroxydisulfate, 2-hydroxy-2-methyl-1-[4-(2-hydroxyl-oxethyl) phenyl] any one in-1-acetone;

Described interior oil phase or middle oil phase are the one in the first oil phase, the second oil phase, the 3rd oil phase, the 4th oil phase, and the compound method of the first oil phase, the second oil phase, the 3rd oil phase, the 4th oil phase is as follows:

The first oil phase: in room temperature, soybean oil, Ergol and poly-ricinoleic acid glyceride are mixed, then add terephthalaldehyde, stir terephthalaldehyde is dissolved completely; The volume ratio of described soybean oil and Ergol is (0.5～1): 1, poly-ricinoleic acid glyceride quality: gross mass=(0.01～0.025) of soybean oil and Ergol: 1, the quality of terephthalaldehyde: gross mass=(0.005～0.025) of soybean oil and Ergol: 1;

The second oil phase: soybean oil, Ergol and poly-ricinoleic acid glyceride are mixed in room temperature; The volume ratio of soybean oil and Ergol is (0.5～1): 1, and the quality of poly-ricinoleic acid glyceride: gross mass=(0.015～0.025) of soybean oil and Ergol: 1;

The 3rd oil phase: in room temperature, soybean oil, Ergol and poly-ricinoleic acid glyceride are mixed, then add terephthalaldehyde, stir phthalaldehyde is dissolved completely; The volume ratio of described Ergol and soybean oil is (0～1): (0.5～1), the quality of poly-ricinoleic acid glyceride: gross mass=(0.02～0.06) of soybean oil and Ergol: 1, the quality of terephthalaldehyde: gross mass=(0.0015～0.0025) of soybean oil and Ergol: 1;

The 4th oil phase: under room temperature, lucifuge condition, soybean oil, Ergol and poly-ricinoleic acid glyceride are mixed, then add oil-soluble light trigger, stir oil-soluble light trigger is dissolved completely; The volume ratio of soybean oil and Ergol is (0.5～1): 1, the quality of poly-ricinoleic acid glyceride: gross mass=(0.03～0.05) of soybean oil and Ergol: 1, the mass ratio of oil-soluble light trigger and soybean oil is (0.002～0.005): 1;

The compound method of described outer oil phase is: in room temperature, soybean oil and poly-ricinoleic acid glyceride are mixed, the mass ratio of described poly-ricinoleic acid glyceride and soybean oil is (0.04～0.1): 1;

The compound method of described collection oil phase is as follows:

In room temperature, soybean oil and poly-ricinoleic acid glyceride are mixed, then add terephthalaldehyde, stir phthalaldehyde is dissolved completely; The mass ratio of described poly-ricinoleic acid glyceride and soybean oil is (0.04～0.1): 1, and terephthalaldehyde and soybean oil mass ratio are (0.0005～0.002): 1;

Or under room temperature, lucifuge condition, soybean oil and poly-ricinoleic acid glyceride are mixed, then add oil-soluble light trigger, stir oil-soluble light trigger is dissolved completely; The mass ratio of described poly-ricinoleic acid glyceride and soybean oil is (0.04～0.1): 1, and the mass ratio of oil-soluble light trigger and soybean oil is (0.002～0.02): 1;

Described oil-soluble light trigger is two (2,4, the 6-trimethylbenzoyl) phosphine oxides of 2,2-dimethoxy-2-phenyl acetophenone or phenyl.

In said method, the poly-weight average molecular weight of described water soluble shells is no more than 5000Da.

In the step (1) of said method, in injection-tube, First Transition pipe, the second transition conduit, the 3rd transition conduit and collecting pipe, the flow of fluid is respectively 200～350 μ L/h, 400～600 μ L/h, 800～1200 μ L/h, 1600～2400 μ L/h and 4500～9000 μ L/h.

In said method, described cleaning solvent is isopropyl alcohol or ethanol.

In said method, interior oil phase is or/and also contain oil-soluble active material in middle oil phase, described oil-soluble active material can be that medicine (as taxol) or nutriment are (as vitamin A, vitamin D), the five phase quadruple emulsions of preparing when step (1) form after composite microcapsule, interior oil phase and middle oil phase are embedded in composite microcapsule, and separated by the internal layer micro-capsule of composite microcapsule between interior oil phase and middle oil phase, interior oil phase and middle oil phase can not mix mutually, thereby can there is not cross pollution in the active material being dissolved in interior oil phase and middle oil phase.

In said method, the sodium hydrate aqueous solution that adopts concentration to be at least 1mol/L when preparation the first water regulates the pH value of described mixed liquor.

The mechanism of the single composite microcapsule that disperses capsule packing structure of the method for the invention preparation: first prepare monodispersed interior oil phase/interior water/middle oil phase/outer water/outer oil phase five phase quadruple emulsions by capillary microfluidic device; Then the reaction monomers and the crosslinking agent that in interior water or outer water, contain form gelatinous micro-capsule wall by light-initiated generation cross-linking reaction, or the reaction monomers containing in interior water or outer water forms gelatinous micro-capsule wall by light-initiated generation cross-linking reaction, or the reaction monomers containing in interior water or outer water is adjacent the crosslinking agent generation cross-linking reaction containing in oil phase and forms gelatinous micro-capsule wall, obtains composite microcapsule base substrate; Finally washing is removed in composite microcapsule and micro-capsule oil phase around can singly be disperseed the not composite microcapsule of oil-containing, or the oil phase that washing is removed on composite microcapsule outer wall can obtain single composite microcapsule that disperses oil-containing.

The method of the invention can be used various types of microfluidic devices to prepare monodispersed interior oil phase/interior water/middle oil phase/outer water/outer oil phase five phase quadruple emulsions, preferably adopt the capillary microfluidic device of following structure: the structural representation of described capillary microfluidic device is shown in Fig. 2, comprise injection-tube, transition conduit, tube connector and collecting pipe, described injection-tube is made by circular capillaries, its afterbody is processed to taper shape, described transition conduit comprises three grade (first, second, the 3rd transition conduit), made by circular capillaries, its afterbody is processed to taper shape, described tube connector comprises level Four (first, second, the third and fourth tube connector), its inner through hole is square, described collecting pipe is circular capillaries, the afterbody of injection-tube inserts the head of First Transition pipe and connects by the first tube connector, the afterbody of First Transition pipe inserts the head of the second transition conduit and connects by the second tube connector, the afterbody of the second transition conduit inserts the head of the 3rd transition conduit and connects by the 3rd tube connector, the afterbody of the 3rd transition conduit inserts the head of collecting pipe and connects by the 4th tube connector.The preparation method of described capillary microfluidic device can be referring to L.Y.Chu, A.S.Utada, R.K.Shah, J.W.Kim, D.A.Weitz, Angew.Chem.Int.Ed.2007,46,8970.

Compared with prior art, the present invention has following beneficial effect:

1. the invention provides a kind of preparation method of new single composite microcapsule that disperses capsule packing structure, the one-tenth wall fraction generation cross-linking reaction that the method only need to cause five phase quadruple Ruzhongs can one time to produce goes out the inside and outside cyst wall of composite microcapsule, without substep operation, compared with prior art, greatly simplify operating process, thereby be conducive to batch production.

2. the five phase quadruple emulsions that adopt capillary microfluidic device to prepare due to the method for the invention have the monodispersity of height, and disposable carrying out can make inside and outside cyst wall, prepare cyst wall without substep, therefore can not cause the monodispersity of composite microcapsule to reduce, thereby structure and the size homogeneous of the composite microcapsule prepared of the method.

3. prepare the cyst wall of composite microcapsule by cross-linking reaction due to the method for the invention, be different from prior art forms cyst wall mode by electrostatic interaction or close hydrophobic effect self assembly, thereby the stability of the composite microcapsule prepared of the method for the invention is better, be not subject to the destruction of external condition.

4. the various reagent that use due to the method for the invention are nontoxic, safety and environmental protection, therefore the composite microcapsule security performance that prepared by the method is higher, the bag that can be used in medicine, nutriment etc. carries, and in preparation process, can not cause adverse effect to operating personnel and environment, safe and reliable.

5. the different water cross-linking system of the method for the invention capable of choosing multiple is prepared the cyst wall of composite microcapsule, and be not limited to now methodical amphipathy macromolecule system, because the kind of water cross-linking system is more compared with the kind of amphipathy macromolecule system, the method only need to can prepare by changing the water cross-linking system of five phase quadruple emulsions the composite microcapsule of polytype capsule packing structure, thereby the scope of application of the method is wider.

6. the method for the invention can controllably be loaded in different oil-soluble active material bags simultaneously bag and is loaded in same composite microcapsule and do not produce cross pollution, and the cyst material that can have pH or a temperature-responsive by selection is prepared the composite microcapsule that has pH response order and discharge (seeing embodiment 1,3), thermal stimulus response (seeing embodiment 4,7), utilize the controlled order release function of composite microcapsule, composite microcapsule can be applied as the control release vehicle of active material.

Brief description of the drawings

Fig. 1 is the principle schematic that the method for the invention is prepared the composite microcapsule of capsule packing structure, Fig. 1 (A) is five phase quadruple emulsions, Fig. 1 (B) is composite microcapsule base substrate, in figure, the internal layer micro-capsule wall of 1-interior oil phase, 2-interior water, 3-middle oil phase, 4-outer water, 5-outer oil phase, 6-composite microcapsule, the outer microtube cyst wall of 7-composite microcapsule;

Fig. 2 is the structural representation of level Four capillary microfluidic device of the present invention, in figure, 8-injection-tube, the 9-the first tube connector, 10-First Transition pipe, the 11-the second tube connector, the 12-the second transition conduit, the 13-the three tube connector, the 14-the three transition conduit, the 15-the four tube connector, 16-collecting pipe;

Fig. 3 is the high-speed camera microphoto of five phase quadruple emulsion forming processes in embodiment 1, and wherein, figure a, b, c, d represent the different formation stages of five phase quadruple emulsions;

Fig. 4 is single laser co-focusing microphoto that disperses five phase quadruple emulsions prepared by embodiment 1;

Fig. 5 is the laser co-focusing microphoto of the composite microcapsule base substrate prepared of embodiment 1;

Fig. 6 is the laser co-focusing microphoto of the composite microcapsule prepared of embodiment 1, and figure a is that light field microphoto, figure b are that green fluorescence microphoto, figure c are that red fluorescence microphoto, figure d are the compound microphoto of light field, green fluorescence field and red fluorescence field;

Fig. 7 is the laser co-focusing microphoto of composite microcapsule step release of active agent process in the cushioning liquid of pH=3.0 of preparing of embodiment 1;

Fig. 8 is the laser co-focusing microphoto of the five phase quadruple emulsions prepared of embodiment 2;

Fig. 9 is the laser co-focusing microphoto of the composite microcapsule prepared of embodiment 2, and figure a is low multiplication factor, and figure b is high-amplification-factor;

Figure 10 is the laser co-focusing microphoto of swelling course of dissolution in the cushioning liquid of pH=3.0 of the composite microcapsule prepared of embodiment 2;

Figure 11 is the ESEM microphoto after the freeze drying of the composite microcapsule prepared of embodiment 2, on figure a ectomesoderm micro-capsule wall, has cut, and figure b ectomesoderm micro-capsule wall breaks completely;

Figure 12 is the laser co-focusing microphoto of the five phase quadruple emulsions prepared of embodiment 3;

Figure 13 is the laser co-focusing microphoto of the composite microcapsule base substrate prepared of embodiment 3, and figure a is low multiplication factor, and figure b is high-amplification-factor;

Figure 14 is the laser co-focusing microphoto in deionized water of the composite microcapsule prepared of embodiment 3, and figure a is that light field microphoto, figure b are that green fluorescence microphoto, figure c are that red fluorescence microphoto, figure d are the Composite Field microphoto of light field, green fluorescence field and red fluorescence field;

Figure 15 is the laser co-focusing microphoto of the controlled step dispose procedure of composite microcapsule prepared of embodiment 3, figure a is that environment temperature is elevated to 50 DEG C from 25 DEG C, the prominent process of disengaging bag loading wherein of outer field NIPA micro-capsule, figure b is the process that internal layer chitosan microcapsules discharges the oil phase that its bag carries in the cushioning liquid of pH=3.0;

Figure 16 is the laser co-focusing microphoto in deionized water of the composite microcapsule prepared of embodiment 4;

Figure 17 is the balance temperature-sensing property of the composite microcapsule prepared of embodiment 4, and figure a is the micro-photograph of the laser co-focusing of composite microcapsule under different temperatures, internal-and external diameter and the internal-and external diameter of internal layer micro-capsule and the relation curve of temperature of the outer micro-capsule that figure b is composite microcapsule.

Figure 18 is the ESEM microphoto after the composite microcapsule freeze drying prepared of embodiment 4, and on figure a ectomesoderm micro-capsule wall, cut is less, and on figure b ectomesoderm micro-capsule wall, cut is larger;

Figure 19 is the laser co-focusing microphoto of the composite microcapsule prepared of embodiment 5;

Figure 20 is the laser co-focusing microphoto of the dispose procedure of the composite microcapsule prepared of embodiment 5 in the cushioning liquid of pH=3.0, Figure 20 (A) (B) (C) is microphoto in the same time not, and figure (D) is partial enlarged drawing of figure (C);

Figure 21 is the laser co-focusing microphoto of the composite microcapsule prepared of embodiment 6;

Figure 22 is the electron scanning micrograph after the freeze drying of the composite microcapsule prepared of embodiment 6, and the outer microtube cyst wall cut of figure a is less, and the outer microtube cyst wall of figure b breaks completely;

Figure 23 is the laser co-focusing microphoto of the composite microcapsule prepared of embodiment 7;

Figure 24 is that composite microcapsule prepared by embodiment 7 discharges the control of rhodamine B, figure a is not in the same time at 20 DEG C of swelling laser co-focusing microphotos of deionized water ectomesoderm NIPA micro-capsule, and figure b is the fluorescence intensity change curve of internal layer polyethyleneglycol diacrylate micro-capsule;

Figure 25 is the laser co-focusing microphoto of the composite microcapsule prepared of embodiment 8 in 20 DEG C of deionized waters;

Figure 26 is composite microcapsule light micrograph after balance in the deionized water of different temperatures prepared by embodiment 8;

Figure 27 is the composite microcapsule prepared of embodiment 8 internal layer micro-capsule internal-and external diameter and outer micro-capsule internal-and external diameter variation with temperature curve after balance in deionized water.

Detailed description of the invention

By the following examples and by reference to the accompanying drawings the preparation method of single composite microcapsule that disperses capsule packing structure of the present invention is described further.

In following each embodiment, described water soluble chitosan is purchased from the biological Co., Ltd of Jinan Hai get Bei; Described Pluronic F127, Pluronic F108, Pluronic F68 and Pluronic F188 are the addition polymers of polypropylene glycol and oxirane, PluronicF127, Pluronic F108, Pluronic F68, Pluronic F188 are trade name, purchased from Sigma company; Water-soluble light trigger 2-hydroxy-2-methyl-1-[4-(2-hydroxyl-oxethyl) phenyl]-1-acetone adopts the light trigger of commodity IRGACURE2959 by name, purchased from BASF AG; Two (2,4, the 6-trimethylbenzoyl) phosphine oxides of described oil-soluble light trigger phenyl, its CAS is numbered 162881-26-7, adopts the light trigger of commodity IRGACURE819 by name, purchased from BASF AG; Described dyestuff Lumogen F Red300 is Yi Zhong perylene diimide compounds, and Lumogen F Red300 is its trade name, purchased from BASF AG; The black HB of described dyestuff fat is 2,3-dihydro-2,2-dimethyl-6-[[4-(phenylazo)-1-naphthalene] azo] perimidine, purchased from Aladdin reagent company; Described soybean oil is for medical injection rank, purchased from Tieling Beiya Medical Oil Co., Ltd..

In following each embodiment, adopt structure capillary microfluidic device as shown in Figure 2, comprise injection-tube 8, transition conduit, tube connector and collecting pipe 16; Described injection-tube 8 is made by circular glass capillary, and its afterbody is processed to taper shape, and the external diameter of its pipe portion section is that 1.0mm, internal diameter are 550 μ m, and its conical portion section outer end diameter is 80 μ m; Described transition conduit comprises three grades (first, second, third transition conduit), made by circular glass capillary, its afterbody is processed to taper shape, the external diameter of First Transition pipe 10 pipe portion sections is that 1.0mm, internal diameter are 190 μ m, its conical portion section inner end diameter is 100 μ m, the external diameter of the second transition conduit 12 pipe portion sections is that 1.0mm, internal diameter are 260 μ m, its conical portion section inner end diameter is 160 μ m, the external diameter of the 3rd transition conduit 14 pipe portion sections is that 1.0mm, internal diameter are 280 μ m, and its conical portion section inner end diameter is 200 μ m; Described tube connector comprises level Four (first, second, third and the 4th tube connector), and its inner through hole is square, and clear size of opening is 1.0mm × 1.0mm; Described collecting pipe 16 is circular capillaries, and its external diameter is 1.0mm, and internal diameter is 500 μ m; The afterbody of injection-tube insert the head of First Transition pipe and by the first tube connector 9 connect, the afterbody of First Transition pipe inserts the head of the second transition conduit and by the second tube connector 11 connect, the afterbody of the second transition conduit inserts the head of the 3rd transition conduit and by the 3rd tube connector 13 connect, the afterbody of the 3rd transition conduit inserts the head of collecting pipe and connects by the 4th tube connector 15.Use AB glue that tube connector and transition conduit, injection-tube, receiving tube are fixed together.

Use this level Four capillary microfluidic device to prepare the method for monodispersed interior oil phase/interior water/middle oil phase/outer water/outer oil phase five phase quadruple emulsions as follows: interior oil phase 1 to be injected under the promotion of syringe pump to injection-tube 8 by syringe, interior water 2 is injected to First Transition pipe 10 from the first tube connector 9 by syringe under the promotion of syringe pump, form oil-in-water (O/W) emulsion of monodispersity at First Transition tube inlet place, middle oil phase 3 injects second transition conduit 12 from the second tube connector 11 by syringe under the promotion of syringe pump, enter Water-In-Oil bag oil (O/W/O) emulsion of interruption-forming monodispersity in the second transition conduit, outer water 4 injects three transition conduit 14 from the 3rd tube connector 13 by syringe under the promotion of syringe pump, form W/O/W bag oil (O/W/O/W) emulsion of monodispersity in the 3rd transition conduit porch, outer oil phase 5 injects collecting pipe 16 from the 4th tube connector 15 by syringe under the promotion of syringe pump, form Water-In-Oil bag Water-In-Oil bag oil (O/W/O/W/O) the five phase quadruple emulsions of monodispersity in the porch of collecting pipe, oil phase/interior water/middle oil phase/outer water/outer oil phase five phase quadruple emulsions in, the five phase quadruple emulsions that form are introduced in the container that fills collection oil phase by exporting with collecting pipe the pipe fitting being connected.

Embodiment 1

The single composite microcapsule that disperses the chitosan microcapsules bag of oil-containing to carry chitosan microcapsules of the present embodiment preparation, processing step is as follows:

(1) prepare five phase quadruple emulsions

1) preparation water and oil phase fluid

The first water: the water soluble chitosan that is 5000Da by weight average molecular weight in room temperature, water soluble emulsifier Pluronic F127, water-soluble thickener hydroxyethylcellulose adds in deionized water, stirring makes water soluble chitosan, Pluronic F127, hydroxyethylcellulose dissolves formation mixed liquor completely, then regulating the pH value of described mixed liquor with the sodium hydrate aqueous solution that concentration is 1.5mol/L is 6.3 to form the first water, the mass ratio of described water soluble chitosan and deionized water is 0.06:1, the mass ratio of Pluronic F127 and deionized water is 0.020:1, the mass ratio of hydroxyethylcellulose and deionized water is 0.02:1,

Interior oil phase (the first oil phase): in room temperature by soybean oil, Ergol and poly-ricinoleic acid glyceride mix, then add terephthalaldehyde and the black HB of oil-soluble active material fat, stirring is dissolved terephthalaldehyde and fatty black HB completely and is formed interior oil phase, the volume ratio of described soybean oil and Ergol is 1:1, poly-ricinoleic acid glyceride quality: the gross mass=0.025:1 of soybean oil and Ergol, the quality of terephthalaldehyde: the gross mass=0.025:1 of soybean oil and Ergol, the black HB quality of fat: the gross mass of soybean oil and Ergol is=0.001:1,

Middle oil phase (the 3rd oil phase): soybean oil, Ergol and poly-ricinoleic acid glyceride are mixed in room temperature, then add terephthalaldehyde and oil-soluble active material Lumogen Red300, stir and make terephthalaldehyde and Lumogen Red300 dissolve the middle oil phase of i.e. formation completely; The volume ratio of described Ergol and soybean oil is 1:1, the quality of poly-ricinoleic acid glyceride: the gross mass=0.06:1 of soybean oil and Ergol, the quality of terephthalaldehyde: the gross mass=0.0025:1 of soybean oil and Ergol, the quality of Lumogen Red300: the gross mass=0.001:1 of soybean oil and Ergol;

Outer oil phase: in room temperature, soybean oil and poly-ricinoleic acid glyceride are mixed and obtain outer oil phase, the mass ratio of described poly-ricinoleic acid glyceride and soybean oil is 0.1:1;

Collect oil phase: in room temperature, soybean oil and poly-ricinoleic acid glyceride are mixed, then add terephthalaldehyde, stir and make phthalaldehyde dissolve i.e. formation collection oil phase completely; The mass ratio of described poly-ricinoleic acid glyceride and soybean oil is 0.1:1, and terephthalaldehyde and soybean oil mass ratio are 0.002:1.

2) prepare five phase quadruple emulsions

Taking the first water as interior water with outer water, by interior oil phase, interior water, middle oil phase, outer water, in outer oil phase difference inhalation syringe, under the promotion of syringe pump, inject evenly the injection-tube of capillary microfluidic device, First Transition pipe, the second transition conduit, in the 3rd transition conduit and collecting pipe, form monodispersed interior oil phase/interior water/middle oil phase/outer water/outer oil phase five phase quadruple emulsions (as shown in Figure 3), then this five phases quadruple emulsion is introduced in the container that fills collection oil phase (seeing Fig. 4) by exporting with capillary microfluidic device collecting pipe the pipe fitting being connected,

In injection-tube, First Transition pipe, the second transition conduit, the 3rd transition conduit and collecting pipe, the flow of each fluid is respectively 200 μ L/h, 400 μ L/h, 800 μ L/h, 1600. μ L/h and 4500 μ L/h.

(2) prepare composite microcapsule base substrate

Step (1) gained five phase quadruple emulsions are left standstill to 2h in room temperature, and shitosan and terephthalaldehyde generation cross-linking reaction formation chitosan microcapsules bag carry the composite microcapsule base substrate of chitosan microcapsules, see Fig. 5.

(3) washing

With deionized water soaking step (2) gained composite microcapsule base substrate 10min, then pour out supernatant liquid to remove the oil phase on composite microcapsule outer wall, obtain single composite microcapsule that disperses the chitosan microcapsules bag of oil-containing to carry shitosan.

The present embodiment is prepared the laser co-focusing microphoto of composite microcapsule in deionized water as shown in Figure 6, Fig. 6 a is light field microphoto, Fig. 6 b is green fluorescence microphoto, and Fig. 6 c is red fluorescence microphoto, and Fig. 6 d is the microphoto after light field, green fluorescence and red fluorescence stack; Green fluorescence is that the shitosan being cross-linked by terephthalaldehyde sends, and red fluorescence is sent by Lumogen Red300; Can see that from Fig. 6 composite microcapsule prepared by the present embodiment has structure and size and the good sphericity of homogeneous, and different oil-soluble active material lays respectively in internal layer micro-capsule and between ectonexine micro-capsule, mutual composite pollution does not occur.

At room temperature, the present embodiment is prepared to the cushioning liquid (citric acid-disodium hydrogen phosphate buffer solution of 0.01mol/L) that composite microcapsule is placed in pH=3.0, use its dispose procedure of confocal laser scanning microscope (seeing Fig. 7), As time goes on, then the outer micro-capsule of composite microcapsule is progressively swelling dissolves, discharge the oil phase that contains Lumogen Red300, then internal layer micro-capsule contacts with the cushioning liquid of pH=3.0, then internal layer micro-capsule is progressively swelling discharges the oil phase that contains fatty black HB after dissolving, show that the composite microcapsule that chitosan microcapsules bag carries chitosan microcapsules has pH response order release function.

Embodiment 2

The present embodiment preparation singly disperses the chitosan microcapsules bag of oil-containing not to carry the composite microcapsule of chitosan microcapsules, and processing step is as follows:

(1) prepare five phase quadruple emulsions

1) preparation water and oil phase fluid

The first water: the water soluble chitosan that is 4000Da by weight average molecular weight in room temperature, water soluble emulsifier Pluronic F108, water-soluble thickener hydroxyethylcellulose adds in deionized water, stirring makes water soluble chitosan, Pluronic F108, hydroxyethylcellulose dissolves formation mixed liquor completely, then regulating the pH value of described mixed liquor with the sodium hydrate aqueous solution that concentration is 1mol/L is 6.7 to form the first water, the mass ratio of described water soluble chitosan and deionized water is 0.02:1, the mass ratio of Pluronic F108 and deionized water is 0.0025:1, the mass ratio of hydroxyethylcellulose and deionized water is 0.01:1,

Interior oil phase (the first oil phase): soybean oil, Ergol and poly-ricinoleic acid glyceride are mixed in room temperature, then add terephthalaldehyde, stirring is dissolved terephthalaldehyde completely and is formed interior oil phase, the volume ratio of described soybean oil and Ergol is 0.5:1, poly-ricinoleic acid glyceride quality: the gross mass=0.01:1 of soybean oil and Ergol, the quality of terephthalaldehyde: the gross mass=0.005:1 of soybean oil and Ergol;

Middle oil phase (the 3rd oil phase): in room temperature, soybean oil, Ergol and poly-ricinoleic acid glyceride are mixed, then add terephthalaldehyde, stir and make terephthalaldehyde dissolve the middle oil phase of i.e. formation completely; The volume ratio of described Ergol and soybean oil is 1:0.5, the quality of poly-ricinoleic acid glyceride: the gross mass=0.03:1 of soybean oil and Ergol, the quality of terephthalaldehyde: the gross mass=0.0015:1 of soybean oil and Ergol;

Outer oil phase: in room temperature, soybean oil and poly-ricinoleic acid glyceride are mixed and obtain outer oil phase, the mass ratio of described poly-ricinoleic acid glyceride and soybean oil is 0.04:1;

Collect oil phase: in room temperature, soybean oil and poly-ricinoleic acid glyceride are mixed, then add terephthalaldehyde, stir and make phthalaldehyde dissolve i.e. formation collection oil phase completely; The mass ratio of described poly-ricinoleic acid glyceride and soybean oil is 0.04:1, and terephthalaldehyde and soybean oil mass ratio are 0.0005:1.

2) prepare five phase quadruple emulsions

Taking the first water as interior water with outer water, by in interior oil phase, interior water, middle oil phase, outer water, outer oil phase difference inhalation syringe, under the promotion of syringe pump, inject evenly injection-tube, First Transition pipe, the second transition conduit, the 3rd transition conduit and the collecting pipe of capillary microfluidic device, form monodispersed interior oil phase/interior water/middle oil phase/outer water/outer oil phase five phase quadruple emulsions, then this five phases quadruple emulsion is introduced in the container that fills collection oil phase (seeing Fig. 8) by exporting with capillary microfluidic device collecting pipe the pipe fitting being connected;

In injection-tube, First Transition pipe, the second transition conduit, the 3rd transition conduit and collecting pipe, the flow of each fluid is respectively 350 μ L/h, 600 μ L/h, 1200 μ L/h, 2400. μ L/h and 9000 μ L/h.

(2) prepare composite microcapsule base substrate

Step (1) gained five phase quadruple emulsions are left standstill to 1h in room temperature, and shitosan and terephthalaldehyde generation cross-linking reaction formation chitosan microcapsules bag carry the composite microcapsule base substrate of chitosan microcapsules.

(3) washing

With washed with isopropyl alcohol step (2) gained composite microcapsule base substrate 6 times, to remove in composite microcapsule and micro-capsule oil phase around, then wash 6 times by deionized water, with remove remain on composite microcapsule wall and micro-capsule in isopropyl alcohol, singly disperseed the chitosan microcapsules bag of oil-containing not to carry the composite microcapsule of chitosan microcapsules, its laser co-focusing microphoto as shown in Figure 9;

The composite microcapsule of in room temperature being prepared by the present embodiment is put into the cushioning liquid (citric acid-disodium hydrogen phosphate buffer solution of 0.01mol/L) of pH=3.0, use the variation of its pattern of confocal laser scanning microscope and structure, as shown in figure 10, As time goes on, internal layer and outer micro-capsule are all swelling gradually in the cushioning liquid of pH=3.0, then subside, finally in the time putting into about 90 seconds of buffer solution, composite microcapsule dissolves completely.

The present embodiment is prepared after composite microcapsule freeze drying and observed with electronic scanner microscope, and its stereoscan photograph as shown in figure 11, can significantly be observed chitosan microcapsules bag and carry the composite construction of chitosan microcapsules from Figure 11.

Embodiment 3

The single composite microcapsule that disperses the NIPA micro-capsule bag of oil-containing to carry chitosan microcapsules of the present embodiment preparation, processing step is as follows:

(1) prepare five phase quadruple emulsions

1) preparation water and oil phase fluid

The first water: the water soluble chitosan that is 5000Da by weight average molecular weight in room temperature, water soluble emulsifier Pluronic F188, water-soluble thickener hydroxyethylcellulose adds in deionized water, stirring makes water soluble chitosan, Pluronic F188, hydroxyethylcellulose dissolves formation mixed liquor completely, then regulating the pH value of described mixed liquor with the sodium hydrate aqueous solution that concentration is 1mol/L is 6.5 to form the first water, the mass ratio of described water soluble chitosan and deionized water is 0.04:1, the mass ratio of Pluronic F188 and deionized water is 0.01:1, the mass ratio of hydroxyethylcellulose and deionized water is 0.015:1,

The second water: in room temperature, under lucifuge condition by NIPA, N, N-methylene-bisacrylamide, water soluble emulsifier Pluronic F127, water-soluble light trigger azo diisobutyl amidine hydrochloride adds in deionized water, stirring makes NIPA, N, N-methylene-bisacrylamide, Pluronic F127, azo diisobutyl amidine hydrochloride dissolves form the second water completely, the mass ratio of described NIPA and deionized water is 0.102:1, N, the mass ratio of N-methylene-bisacrylamide and deionized water is 0.00924:1, the mass ratio of Pluronic F188 and deionized water is 0.02:1, the mass ratio of azo diisobutyl amidine hydrochloric acid and deionized water is 0.02:1,

Interior oil phase (the first oil phase): in room temperature by soybean oil, Ergol and poly-ricinoleic acid glyceride mix, then add terephthalaldehyde and oil-soluble active material Lumogen Red300, stirring is dissolved terephthalaldehyde and Lumogen Red300 completely and is formed interior oil phase, the volume ratio of described soybean oil and Ergol is 0.9:1, poly-ricinoleic acid glyceride quality: the gross mass=0.02:1 of soybean oil and Ergol, the quality of terephthalaldehyde: the gross mass=0.02:1 of soybean oil and Ergol, the quality of Lumogen Red300: the gross mass=0.001:1 of soybean oil and Ergol,

Middle oil phase (the 3rd oil phase): in room temperature, soybean oil and poly-ricinoleic acid glyceride are mixed, then add terephthalaldehyde, stir and make terephthalaldehyde dissolve the middle oil phase of i.e. formation completely; The quality of described poly-ricinoleic acid glyceride: the quality=0.02:1 of soybean oil, the quality of terephthalaldehyde: the quality=0.0015:1 of soybean oil;

Outer oil phase: in room temperature, soybean oil and poly-ricinoleic acid glyceride are mixed and obtain outer oil phase, the mass ratio of described poly-ricinoleic acid glyceride and soybean oil is 0.05:1;

Collect oil phase: under room temperature, lucifuge condition, soybean oil and poly-ricinoleic acid glyceride are mixed, then add oil-soluble light trigger 2,2-dimethoxy-2-phenyl acetophenone, stirs and makes 2,2-dimethoxy-2-phenyl acetophenone dissolve i.e. formation collection oil phase completely; The mass ratio of described poly-ricinoleic acid glyceride and soybean oil is 0.04:1, and the mass ratio of 2,2-dimethoxy-2-phenyl acetophenone and soybean oil is 0.002:1.

2) prepare five phase quadruple emulsions

Taking the first water as interior water, the second water is outer water, under lucifuge condition by interior oil phase, interior water, middle oil phase, outer water, in outer oil phase difference inhalation syringe, under the promotion of syringe pump, inject evenly the injection-tube of capillary microfluidic device, First Transition pipe, the second transition conduit, in the 3rd transition conduit and collecting pipe, form monodispersed interior oil phase/interior water/middle oil phase/outer water/outer oil phase five phase quadruple emulsions, then this five phases quadruple emulsion is introduced in the container that fills collection oil phase by exporting with capillary microfluidic device collecting pipe the pipe fitting being connected, its laser co-focusing microphoto as shown in figure 12,

In injection-tube, First Transition pipe, the second transition conduit, the 3rd transition conduit and collecting pipe, the flow of each fluid is respectively 260 μ L/h, 470 μ L/h, 1000 μ L/h, 2000 μ L/h and 7000 μ L/h.

(2) prepare composite microcapsule base substrate

Step (1) gained five phase quadruple emulsions (are placed in to mixture of ice and water at ice bath, temperature is about 2～4 DEG C) adopt UV-irradiation 10min under condition, then leave standstill 1h in room temperature, NIPA and N, N-methylene-bisacrylamide generation cross-linking reaction, shitosan and terephthalaldehyde generation cross-linking reaction formation NIPA micro-capsule bag carry the composite microcapsule base substrate of chitosan microcapsules, and its laser co-focusing microphoto as shown in figure 13.

(3) washing

With deionized water soaking step (2) gained composite microcapsule base substrate 10min, then pour out supernatant liquid to remove the oil phase on composite microcapsule outer wall, obtain single composite microcapsule that disperses the NIPA micro-capsule bag of oil-containing to carry chitosan microcapsules.

Composite microcapsule prepared by the present embodiment laser co-focusing microphoto in 25 DEG C of deionized waters as shown in figure 14, Figure 14 a is light field microphoto, Figure 14 b is green fluorescence microphoto, Figure 14 c is red fluorescence microphoto, and Figure 14 d is the microphoto after light field, green fluorescence and red fluorescence stack; Green fluorescence is that the shitosan being cross-linked by terephthalaldehyde sends, and red fluorescence is sent by Lumogen Red300; Have structure and size and the good sphericity of homogeneous from the known composite microcapsule of this figure, bag is loaded in same internal layer micro-capsule, composite pollution phenomenon does not occur for different oil phases between internal layer and outer micro-capsule.

Under laser confocal microscope, observe the temperature of composite microcapsule and the step release performance of pH response prepared by the present embodiment, see Figure 15, composite microcapsule is placed in to the aqueous solution of pH=6.5, in the time that the temperature of the described aqueous solution is elevated to 50 DEG C from 25 DEG C, NIPA micro-capsule shrinks, because the material that in NIPA micro-capsule, bag carries can not see through cystoblast, do not there is compressibility yet, in the time that the pressure of NIPA micro-capsule inside exceedes the pressure that its cyst wall can bear, the all substances that NIPA micro-capsule wraps its inner institute year are discharged in environment (sees Figure 15 a), the oil phase being loaded between inner chitosan microcapsules and ectonexine micro-capsule by bag in this dispose procedure is released, thereby the temperature control that completes its first stage discharges, then the pH value of the described aqueous solution is adjusted to 3.0, chitosan microcapsules is swelling gradually, finally dissolves completely, discharges the oily core that its inner bag carries, and the control that completes second stage discharges (sees Figure 15 b).

Embodiment 4

The present embodiment preparation singly disperses the NIPA micro-capsule bag of oil-containing not to carry the composite microcapsule of chitosan microcapsules, and processing step is as follows:

(1) prepare five phase quadruple emulsions

1) preparation water and oil phase fluid

The first water: the water soluble chitosan that is 3000Da by weight average molecular weight in room temperature, water soluble emulsifier Pluronic F68, water-soluble thickener hydroxyethylcellulose adds in deionized water, stirring makes water soluble chitosan, Pluronic F68, hydroxyethylcellulose dissolves formation mixed liquor completely, then regulating the pH value of described mixed liquor with the sodium hydrate aqueous solution that concentration is 1mol/L is 6.4 to form the first water, the mass ratio of described water soluble chitosan and deionized water is 0.04:1, the mass ratio of Pluronic F68 and deionized water is 0.0025:1, the mass ratio of hydroxyethylcellulose and deionized water is 0.015:1,

The second water: in room temperature, under lucifuge condition by NIPA, N, N-methylene-bisacrylamide, water soluble emulsifier Pluronic F68, water-soluble light trigger azo diisobutyl amidine hydrochloride adds in deionized water, stirring makes NIPA, N, N-methylene-bisacrylamide, Pluronic F68, azo diisobutyl amidine hydrochloride dissolves form the second water completely, the mass ratio of described NIPA and deionized water is 0.124:1, N, the mass ratio of N-methylene-bisacrylamide and deionized water is 0.00616:1, the mass ratio of Pluronic F68 and deionized water is 0.0025:1, the mass ratio of azo diisobutyl amidine hydrochloric acid and deionized water is 0.004:1,

Interior oil phase (the first oil phase): soybean oil, Ergol and poly-ricinoleic acid glyceride are mixed in room temperature, then add terephthalaldehyde, stirring is dissolved terephthalaldehyde completely and is formed interior oil phase, the volume ratio of described soybean oil and Ergol is 0.85:1, poly-ricinoleic acid glyceride quality: the gross mass=0.025:1 of soybean oil and Ergol, the quality of terephthalaldehyde: the gross mass=0.015:1 of soybean oil and Ergol;

Middle oil phase (the 3rd oil phase): in room temperature, soybean oil, Ergol and poly-ricinoleic acid glyceride are mixed, then add terephthalaldehyde, stir and make terephthalaldehyde dissolve the middle oil phase of i.e. formation completely; The volume ratio of described Ergol and soybean oil is 1:1, the quality of poly-ricinoleic acid glyceride: the gross mass=0.05:1 of soybean oil and Ergol, the quality of terephthalaldehyde: the gross mass=0.0025:1 of soybean oil and Ergol;

Collect oil phase: under room temperature, lucifuge condition, soybean oil and poly-ricinoleic acid glyceride are mixed, then add oil-soluble light trigger 2,2-dimethoxy-2-phenyl acetophenone, stirs and makes 2,2-dimethoxy-2-phenyl acetophenone dissolve i.e. formation collection oil phase completely; The mass ratio of described poly-ricinoleic acid glyceride and soybean oil is 0.1:1, and the mass ratio of 2,2-dimethoxy-2-phenyl acetophenone and soybean oil is 0.005:1.

2) prepare five phase quadruple emulsions

Taking the first water as interior water, the second water is outer water, under lucifuge condition by interior oil phase, interior water, middle oil phase, outer water, in outer oil phase difference inhalation syringe, under the promotion of syringe pump, inject evenly the injection-tube of capillary microfluidic device, First Transition pipe, the second transition conduit, in the 3rd transition conduit and collecting pipe, form monodispersed interior oil phase/interior water/middle oil phase/outer water/outer oil phase five phase quadruple emulsions, then this five phases quadruple emulsion is introduced in the container that fills collection oil phase by exporting with capillary microfluidic device collecting pipe the pipe fitting being connected,

In injection-tube, First Transition pipe, the second transition conduit, the 3rd transition conduit and collecting pipe, the flow of each fluid is respectively 220 μ L/h, 420 μ L/h, 980 μ L/h, 1700 μ L/h and 6000 μ L/h.

(2) prepare composite microcapsule base substrate

Step (1) gained five phase quadruple emulsions (are placed in to mixture of ice and water at ice bath, temperature is about 2～4 DEG C) adopt UV-irradiation 25min under condition, then leave standstill 1h in room temperature, NIPA and N, N-methylene-bisacrylamide generation cross-linking reaction, shitosan and terephthalaldehyde generation cross-linking reaction formation NIPA micro-capsule bag carry the composite microcapsule base substrate of chitosan microcapsules.

(3) washing

With ethanol washing composite microcapsule base substrate 8 times, to remove in composite microcapsule and micro-capsule oil phase around, then wash 8 times by deionized water, removal remain on composite microcapsule wall and micro-capsule in ethanol, singly disperseed the NIPA micro-capsule bag of oil-containing not to carry the composite microcapsule of chitosan microcapsules, Figure 16 is shown in by its laser co-focusing microphoto in 20 DEG C of deionized waters.

Composite microcapsule prepared by the present embodiment is placed in the deionized water of 20 DEG C, 24 DEG C, 28 DEG C, 32 DEG C, 36 DEG C and 40 DEG C, observe its pattern and structure by laser co-focusing, and measure the internal-and external diameter of internal layer micro-capsule and the internal-and external diameter of outer micro-capsule, result as shown in figure 17, outer field NIPA micro-capsule shows good Thermo-sensitive (seeing two curves above in Figure 17 b), and inner chitosan microcapsules does not have Thermo-sensitive (two curves below seeing in Figure 17 b).

To after composite microcapsule freeze drying prepared the present embodiment, use sem observation, its electron scanning micrograph is shown in Figure 18, can significantly observe the composite construction of this micro-capsule from this figure.

Embodiment 5

The single composite microcapsule that disperses the chitosan microcapsules bag of oil-containing to carry polyethyleneglycol diacrylate micro-capsule of the present embodiment preparation, processing step is as follows:

(1) prepare five phase quadruple emulsions

1) preparation water and oil phase fluid

The first water: the water soluble chitosan that is 5000Da by weight average molecular weight in room temperature, water soluble emulsifier Pluronic F127, water-soluble thickener hydroxyethylcellulose adds in deionized water, stirring makes water soluble chitosan, Pluronic F127, hydroxyethylcellulose dissolves formation mixed liquor completely, then regulating the pH value of described mixed liquor with the sodium hydrate aqueous solution that concentration is 1.5mol/L is 6.5 to form the first water, the mass ratio of described water soluble chitosan and deionized water is 0.04:1, the mass ratio of Pluronic F127 and deionized water is 0.01:1, the mass ratio of hydroxyethylcellulose and deionized water is 0.012:1,

The 3rd water: under room temperature, lucifuge condition, polyethyleneglycol diacrylate, water soluble emulsifier Pluronic F127, water-soluble light trigger azo diisobutyl amidine hydrochloride are added in deionized water, stir and make polyethyleneglycol diacrylate, Pluronic F127, azo diisobutyl amidine hydrochloride dissolve formation the 3rd water completely; The mass ratio of described polyethyleneglycol diacrylate and deionized water is 0.2:1, and the mass ratio of Pluronic F127 and deionized water is 0.02:1, and the mass ratio of azo diisobutyl amidine hydrochloride and deionized water is 0.02:1;

Interior oil phase (the second oil phase): in room temperature, soybean oil, Ergol and poly-ricinoleic acid glyceride are mixed to oil phase in i.e. formation; The volume ratio of soybean oil and Ergol is 1:1, the quality of poly-ricinoleic acid glyceride: the gross mass=0.025:1 of soybean oil and Ergol;

Middle oil phase (the 4th oil phase): under room temperature, lucifuge condition, soybean oil, Ergol and poly-ricinoleic acid glyceride are mixed, then add oil-soluble light trigger 2,2-dimethoxy-2-phenyl acetophenone, stirring is dissolved 2,2-dimethoxy-2-phenyl acetophenone completely and is formed middle oil phase; The volume ratio of soybean oil and Ergol is 1:1, the quality of poly-ricinoleic acid glyceride: the gross mass=0.05:1 of soybean oil and Ergol, and the mass ratio of 2,2-dimethoxy-2-phenyl acetophenone and soybean oil is 0.005:1;

Outer oil phase: in room temperature, soybean oil and poly-ricinoleic acid glyceride are mixed and obtain outer oil phase, the mass ratio of described poly-ricinoleic acid glyceride and soybean oil is 0.08:1;

Collect oil phase: in room temperature, soybean oil and poly-ricinoleic acid glyceride are mixed, then add terephthalaldehyde, stir and make phthalaldehyde dissolve i.e. formation collection oil phase completely; The mass ratio of described poly-ricinoleic acid glyceride and soybean oil is 0.08:1, and terephthalaldehyde and soybean oil mass ratio are 0.0015:1.

2) prepare five phase quadruple emulsions

Taking the 3rd water as interior water, the first water is outer water, under lucifuge condition by interior oil phase, interior water, middle oil phase, outer water, in outer oil phase difference inhalation syringe, under the promotion of syringe pump, inject evenly the injection-tube of capillary microfluidic device, First Transition pipe, the second transition conduit, in the 3rd transition conduit and collecting pipe, form monodispersed interior oil phase/interior water/middle oil phase/outer water/outer oil phase five phase quadruple emulsions, then this five phases quadruple emulsion is introduced in the container that fills collection oil phase by exporting with capillary microfluidic device collecting pipe the pipe fitting being connected,

In injection-tube, First Transition pipe, the second transition conduit, the 3rd transition conduit and collecting pipe, the flow of each fluid is respectively 300 μ L/h, 500 μ L/h, 1100 μ L/h, 1900 μ L/h and 7500 μ L/h.

(2) prepare composite microcapsule base substrate

Step (1) gained five phase quadruple emulsions (are placed in to mixture of ice and water at ice bath, temperature is about 2～4 DEG C) adopt UV-irradiation 25min under condition, then leave standstill 1h in room temperature, polyethyleneglycol diacrylate generation cross-linking reaction, shitosan and terephthalaldehyde generation cross-linking reaction formation chitosan microcapsules bag carry the composite microcapsule base substrate of polyethyleneglycol diacrylate micro-capsule.

(3) washing

With deionized water soaking step (2) gained composite microcapsule base substrate 10min, then pour out supernatant liquid to remove the oil phase on composite microcapsule outer wall, obtain single composite microcapsule that disperses the chitosan microcapsules bag of oil-containing to carry polyethyleneglycol diacrylate micro-capsule, its laser co-focusing microphoto in deionized water as shown in figure 19.

Composite microcapsule prepared by the present embodiment is placed in the cushioning liquid (citric acid-disodium hydrogen phosphate buffer solution of 0.01mol/L) of pH=3.0, under laser confocal microscope, observe its dispose procedure, see Figure 20, outer chitosan microcapsules is swelling gradually in the cushioning liquid of pH=3.0, final dissolving, discharge between two-layer micro-capsule oil phase that bag carries and the polyethyleneglycol diacrylate micro-capsule of internal layer, polyethyleneglycol diacrylate micro-capsule is more stable in acidity.

Embodiment 6

The present embodiment preparation singly disperses the chitosan microcapsules bag of oil-containing not to carry the composite microcapsule of polyethyleneglycol diacrylate micro-capsule, and processing step is as follows:

(1) prepare five phase quadruple emulsions

1) preparation water and oil phase fluid

The first water: the water soluble chitosan that is 5000Da by weight average molecular weight in room temperature, water soluble emulsifier Pluronic F188, water-soluble thickener hydroxyethylcellulose adds in deionized water, stirring makes water soluble chitosan, Pluronic F188, hydroxyethylcellulose dissolves formation mixed liquor completely, then regulating the pH value of described mixed liquor with the sodium hydrate aqueous solution that concentration is 1.5mol/L is 6.5 to form the first water, the mass ratio of described water soluble chitosan and deionized water is 0.04:1, the mass ratio of Pluronic F188 and deionized water is 0.01:1, the mass ratio of hydroxyethylcellulose and deionized water is 0.015:1,

The 3rd water: under room temperature, lucifuge condition, polyethyleneglycol diacrylate, water soluble emulsifier Pluronic F188, water-soluble light trigger azo diisobutyl amidine hydrochloride are added in deionized water, stir and make polyethyleneglycol diacrylate, Pluronic F188, azo diisobutyl amidine hydrochloride dissolve formation the 3rd water completely; The mass ratio of described polyethyleneglycol diacrylate and deionized water is 0.06:1, and the mass ratio of Pluronic F188 and deionized water is 0.005:1, and the mass ratio of azo diisobutyl amidine hydrochloride and deionized water is 0.0025:1;

Interior oil phase (the second oil phase): in room temperature, soybean oil, Ergol and poly-ricinoleic acid glyceride are mixed to oil phase in i.e. formation; The volume ratio of soybean oil and Ergol is 0.5:1, the quality of poly-ricinoleic acid glyceride: the gross mass=0.015:1 of soybean oil and Ergol;

Middle oil phase (the 4th oil phase): under room temperature, lucifuge condition, soybean oil, Ergol and poly-ricinoleic acid glyceride are mixed, then add oil-soluble light trigger 2,2-dimethoxy-2-phenyl acetophenone, stirring is dissolved 2,2-dimethoxy-2-phenyl acetophenone completely and is formed middle oil phase; The volume ratio of soybean oil and Ergol is 0.5:1, the quality of poly-ricinoleic acid glyceride: the gross mass=0.03:1 of soybean oil and Ergol, and the mass ratio of 2,2-dimethoxy-2-phenyl acetophenone and soybean oil is 0.002:1;

Outer oil phase: in room temperature, soybean oil and poly-ricinoleic acid glyceride are mixed and obtain outer oil phase, the mass ratio of described poly-ricinoleic acid glyceride and soybean oil is 0.075:1;

Collect oil phase: in room temperature, soybean oil and poly-ricinoleic acid glyceride are mixed, then add terephthalaldehyde, stir and make phthalaldehyde dissolve i.e. formation collection oil phase completely; The mass ratio of described poly-ricinoleic acid glyceride and soybean oil is 0.075:1, and terephthalaldehyde and soybean oil mass ratio are 0.0015:1;

2) prepare five phase quadruple emulsions

In injection-tube, First Transition pipe, the second transition conduit, the 3rd transition conduit and collecting pipe, the flow of each fluid is respectively 320 μ L/h, 550 μ L/h, 1100 μ L/h, 2200 μ L/h and 8500 μ L/h.

(2) prepare composite microcapsule base substrate

(3) washing

With washed with isopropyl alcohol step (2) gained composite microcapsule base substrate 7 times, to remove in composite microcapsule and micro-capsule oil phase around, then with deionized water wash 7 times with remove remain on composite microcapsule wall and micro-capsule in isopropyl alcohol, the composite microcapsule that is singly disperseed not carry containing oil phase chitosan microcapsules bag polyethyleneglycol diacrylate micro-capsule, its laser co-focusing microphoto in 20 DEG C of deionized waters as shown in figure 21.

After composite microcapsule freeze drying prepared by the present embodiment, with scanning electron microscopic observation, its stereoscan photograph as shown in figure 22.

Embodiment 7

The present embodiment preparation singly disperses the NIPA micro-capsule bag of oil-containing not to carry the composite microcapsule of polyethyleneglycol diacrylate micro-capsule, and processing step is as follows:

(1) prepare five phase quadruple emulsions

1) preparation water and oil phase fluid

The second water: in room temperature, under lucifuge condition by NIPA, N, N-methylene-bisacrylamide, water soluble emulsifier Pluronic F108, water-soluble light trigger potassium peroxydisulfate adds in deionized water, stirring makes NIPA, N, N-methylene-bisacrylamide, Pluronic F108, potassium peroxydisulfate dissolves form the second water completely, the mass ratio of described NIPA and deionized water is 0.113:1, N, the mass ratio of N-methylene-bisacrylamide and deionized water is 0.0077:1, the mass ratio of Pluronic F108 and deionized water is 0.005:1, the mass ratio of potassium peroxydisulfate and deionized water is 0.003:1,

The 3rd water: under room temperature, lucifuge condition, polyethyleneglycol diacrylate, water soluble emulsifier Pluronic F108, water-soluble light trigger ammonium persulfate are added in deionized water, stir and make polyethyleneglycol diacrylate, Pluronic F108, ammonium persulfate dissolve formation the 3rd water completely; The mass ratio of described polyethyleneglycol diacrylate and deionized water is 0.06:1, and the mass ratio of Pluronic F108 and deionized water is 0.005:1, and the mass ratio of ammonium persulfate and deionized water is 0.005:1;

Interior oil phase (the second oil phase): in room temperature, soybean oil, Ergol and poly-ricinoleic acid glyceride are mixed to oil phase in i.e. formation; The volume ratio of soybean oil and Ergol is 0.75:1, the quality of poly-ricinoleic acid glyceride: the gross mass=0.02:1 of soybean oil and Ergol;

Middle oil phase (the 4th oil phase): under room temperature, lucifuge condition, soybean oil, Ergol and poly-ricinoleic acid glyceride are mixed, then add oil-soluble light trigger 2,2-dimethoxy-2-phenyl acetophenone, stirring is dissolved 2,2-dimethoxy-2-phenyl acetophenone completely and is formed middle oil phase; The volume ratio of soybean oil and Ergol is 0.75:1, the quality of poly-ricinoleic acid glyceride: the gross mass=0.04:1 of soybean oil and Ergol, and the mass ratio of 2,2-dimethoxy-2-phenyl acetophenone and soybean oil is 0.002:1;

Outer oil phase: in room temperature, soybean oil and poly-ricinoleic acid glyceride are mixed and obtain outer oil phase, the mass ratio of described poly-ricinoleic acid glyceride and soybean oil is 0.06:1;

Collect oil phase: under room temperature, lucifuge condition, soybean oil and poly-ricinoleic acid glyceride are mixed, then add oil-soluble light trigger 2,2-dimethoxy-2-phenyl acetophenone, stirs and makes 2,2-dimethoxy-2-phenyl acetophenone dissolve i.e. formation collection oil phase completely; The mass ratio of described poly-ricinoleic acid glyceride and soybean oil is 0.06:1, and the mass ratio of 2,2-dimethoxy-2-phenyl acetophenone and soybean oil is 0.005:1;

2) prepare five phase quadruple emulsions

Taking the 3rd water as interior water, the second water is outer water, under lucifuge condition by interior oil phase, interior water, middle oil phase, outer water, in outer oil phase difference inhalation syringe, under the promotion of syringe pump, inject evenly the injection-tube of capillary microfluidic device, First Transition pipe, the second transition conduit, in the 3rd transition conduit and collecting pipe, form monodispersed interior oil phase/interior water/middle oil phase/outer water/outer oil phase five phase quadruple emulsions, then this five phases quadruple emulsion is introduced in the container that fills collection oil phase by exporting with capillary microfluidic device collecting pipe the pipe fitting being connected,

In injection-tube, First Transition pipe, the second transition conduit, the 3rd transition conduit and collecting pipe, the flow of each fluid is respectively 280 μ L/h, 520 μ L/h, 1000 μ L/h, 2100 μ L/h and 8500 μ L/h.

(2) prepare composite microcapsule base substrate

Step (1) gained five phase quadruple emulsions are adopted to UV-irradiation 10min under the water bath condition of 20 DEG C, then leave standstill 10min in room temperature, polyethyleneglycol diacrylate generation cross-linking reaction, NIPA and N, N-methylene-bisacrylamide generation cross-linking reaction formation NIPA micro-capsule bag carries the composite microcapsule base substrate of polyethyleneglycol diacrylate micro-capsule.

(3) washing

With washed with isopropyl alcohol step (2) gained composite microcapsule base substrate 7 times, to remove in composite microcapsule and micro-capsule oil phase around, then with deionized water wash 7 times with remove remain on composite microcapsule wall and micro-capsule in isopropyl alcohol, singly disperseed the NIPA micro-capsule bag of oil-containing not to carry the composite microcapsule of polyethyleneglycol diacrylate micro-capsule, its laser co-focusing microphoto in 20 DEG C of deionized waters as shown in figure 23.

Composite microcapsule prepared by the present embodiment is as the control release vehicle of small-molecule active substance, composite microcapsule is put into the rhodamine B aqueous solution that 20 DEG C, concentration are 0.1wt%, rhodamine B is by diffusing in composite microcapsule, then the temperature of solution is heated to 50 DEG C, outer field NIPA micro-capsule shrinks along with the rising of temperature, and the diameter of the polyethyleneglycol diacrylate micro-capsule of internal layer does not change; The composite microcapsule that is mounted with rhodamine B is transferred in the deionized water of 20 DEG C, the outer micro-capsule of composite microcapsule is swelling, discharge rhodamine B wherein, Figure 24 a is at 20 DEG C of laser co-focusing microphotos that deionized water ectomesoderm micro-capsule is swelling, the fluorescence intensity of measuring rhodamine B in internal layer micro-capsule by laser confocal microscope over time, known rhodamine B is discharged in deionized water rapidly, see Figure 24 b, illustrate that composite microcapsule prepared by the present embodiment can serve as the control release vehicle of small-molecule active substance.

Embodiment 8

The present embodiment preparation singly disperses the NIPA micro-capsule bag of oil-containing not to carry the composite microcapsule of NIPA micro-capsule, and processing step is as follows:

(1) prepare five phase quadruple emulsions

1) preparation water and oil phase fluid

The second water: in room temperature, under lucifuge condition by NIPA, N, N-methylene-bisacrylamide, water soluble emulsifier Pluronic F127, water-soluble light trigger IRGACURE2959 adds in deionized water, stirring makes NIPA, N, N-methylene-bisacrylamide, Pluronic F127, IRGACURE2959 dissolves form the second water completely, the mass ratio of described NIPA and deionized water is 0.113:1, N, the mass ratio of N-methylene-bisacrylamide and deionized water is 0.0077:1, the mass ratio of Pluronic F127 and deionized water is 0.005:1, the mass ratio of IRGACURE2959 and deionized water is 0.01:1,

Interior oil phase (the second oil phase): in room temperature, soybean oil, Ergol and poly-ricinoleic acid glyceride are mixed to oil phase in i.e. formation; The volume ratio of soybean oil and Ergol is 0.857:1, the quality of poly-ricinoleic acid glyceride: the gross mass=0.02:1 of soybean oil and Ergol;

Middle oil phase (the 4th oil phase): under room temperature, lucifuge condition, soybean oil, Ergol and poly-ricinoleic acid glyceride are mixed, then add oil-soluble light trigger IRGACURE819, stir and make IRGACURE819 dissolve the middle oil phase of i.e. formation completely; The volume ratio of soybean oil and Ergol is 0.857:1, the quality of poly-ricinoleic acid glyceride: the gross mass=0.04:1 of soybean oil and Ergol, and the mass ratio of IRGACURE819 and soybean oil is 0.004:1;

Collect oil phase: under room temperature, lucifuge condition, soybean oil and poly-ricinoleic acid glyceride are mixed, then add oil-soluble light trigger 2,2-dimethoxy-2-phenyl acetophenone, stirs and makes 2,2-dimethoxy-2-phenyl acetophenone dissolve i.e. formation collection oil phase completely; The mass ratio of described poly-ricinoleic acid glyceride and soybean oil is 0.05:1, and the mass ratio of 2,2-dimethoxy-2-phenyl acetophenone and soybean oil is 0.005:1;

2) prepare five phase quadruple emulsions

Taking the second water as interior water with outer water, under lucifuge condition, interior oil phase, interior water, middle oil phase, outer water, outer oil phase are distinguished in inhalation syringe, under the promotion of syringe pump, inject evenly injection-tube, First Transition pipe, the second transition conduit, the 3rd transition conduit and the collecting pipe of capillary microfluidic device, form monodispersed interior oil phase/interior water/middle oil phase/outer water/outer oil phase five phase quadruple emulsions, then this five phases quadruple emulsion is introduced in the container that fills collection oil phase by exporting with capillary microfluidic device collecting pipe the pipe fitting being connected;

In injection-tube, First Transition pipe, the second transition conduit, the 3rd transition conduit and collecting pipe, the flow of each fluid is respectively 270 μ L/h, 500 μ L/h, 1100 μ L/h, 2300 μ L/h and 8800 μ L/h.

(2) prepare composite microcapsule base substrate

Step (1) gained five phase quadruple emulsions are adopted to UV-irradiation 15min under 15 DEG C of water bath condition, then leave standstill 10min in room temperature, NIPA and N, N-methylene-bisacrylamide generation cross-linking reaction formation NIPA micro-capsule bag carries the composite microcapsule base substrate of NIPA micro-capsule.

(3) washing

With washed with isopropyl alcohol step (2) gained composite microcapsule base substrate 7 times, to remove in composite microcapsule and micro-capsule oil phase around, then with deionized water wash 7 times with remove remain on composite microcapsule wall and micro-capsule in isopropyl alcohol, singly disperseed the NIPA micro-capsule bag of oil-containing not to carry the composite microcapsule of NIPA micro-capsule, as shown in figure 25, this composite microcapsule has structure and the size of homogeneous to its laser co-focusing microphoto in 20 DEG C of deionized waters as shown in Figure 25.

Composite microcapsule prepared by the present embodiment is placed in respectively the deionized water of 20 DEG C, 23 DEG C, 26 DEG C, 29 DEG C, 32 DEG C, 35 DEG C, 38 DEG C, 41 DEG C and 44 DEG C, after the balance of 30min, with its pattern of observation by light microscope, Figure 26 is the light micrograph of composite microcapsule in 20 DEG C, 26 DEG C, 32 DEG C, 38 DEG C, 44 DEG C deionized waters.After balance 30min, measure internal layer micro-capsule internal-and external diameter and the outer micro-capsule internal-and external diameter of composite microcapsule in the deionized water of each temperature spot, 15 composite microcapsules of each temperature survey calculate average internal layer micro-capsule internal-and external diameter and outer micro-capsule internal-and external diameter, and result as shown in figure 27.By add functional nano particle in internal layer or outer micro-capsule, as gold nanorods, can control respectively the swelling of ectonexine micro-capsule and shrink by infrared and temperature, thereby composite microcapsule of the present invention be expected to as the controlled release release vehicle that can accurately control rate of release.

Claims

1. a preparation method for single composite microcapsule that disperses capsule packing structure, is characterized in that processing step is as follows:

(1) prepare five phase quadruple emulsions

1. prepare the first kind five phase quadruple emulsions

Or 2. prepare Equations of The Second Kind five phase quadruple emulsions

In described interior water, contain reaction monomers, crosslinking agent, light trigger or contain reaction monomers, light trigger, in outer water, contain reaction monomers, crosslinking agent, light trigger or contain reaction monomers, light trigger, two oil phases adjacent with interior water neutralize in two oil phases adjacent with outer water containing reaction monomers and crosslinking agent;

Or in described interior water, contain reaction monomers, crosslinking agent, light trigger or contain reaction monomers, light trigger, in two oil phases adjacent with interior water, do not contain reaction monomers, in outer water, contain reaction monomers but not containing crosslinking agent and light trigger, in two oil phases adjacent with outer water, do not contain reaction monomers but contain crosslinking agent at least one oil phase;

Or in described outer water, contain reaction monomers, crosslinking agent, light trigger or contain reaction monomers, light trigger, in two oil phases adjacent with outer water, do not contain reaction monomers, in interior water, contain reaction monomers but not containing crosslinking agent and light trigger, in two oil phases adjacent with interior water, do not contain reaction monomers but contain crosslinking agent at least one oil phase;

(2) prepare composite microcapsule base substrate

(3) washing

2. singly disperse according to claim 1 the preparation method of the composite microcapsule of capsule packing structure, it is characterized in that in the time in step (2) being reaction monomers and crosslinking agent generation cross-linking reaction formation composite microcapsule, being combined as water soluble chitosan and terephthalaldehyde or being NIPA and N, N-methylene-bisacrylamide of the reaction monomers adopting and crosslinking agent; In the time in step (2) being reaction monomers and reaction monomers generation cross-linking reaction formation composite microcapsule, the reaction monomers adopting is polyethyleneglycol diacrylate.

3. the preparation method who singly disperses according to claim 2 the composite microcapsule of capsule packing structure, is characterized in that:

Described interior water or outer water are the one in the first water, the second water, the 3rd water, and the compound method of the first water, the second water, the 3rd water is as follows:

The 3rd oil phase: in room temperature, soybean oil, Ergol and poly-ricinoleic acid glyceride are mixed, then add terephthalaldehyde, stir terephthalaldehyde is dissolved completely; The volume ratio of described Ergol and soybean oil is (0～1): (0.5～1), the quality of poly-ricinoleic acid glyceride: gross mass=(0.02～0.06) of soybean oil and Ergol: 1, the quality of terephthalaldehyde: gross mass=(0.0015～0.0025) of soybean oil and Ergol: 1;

The compound method of described collection oil phase is as follows:

In room temperature, soybean oil and poly-ricinoleic acid glyceride are mixed, then add terephthalaldehyde, stir terephthalaldehyde is dissolved completely; The mass ratio of described poly-ricinoleic acid glyceride and soybean oil is (0.04～0.1): 1, and the mass ratio of terephthalaldehyde and soybean oil is (0.0005～0.002): 1;

4. according to the preparation method of single composite microcapsule that disperses capsule packing structure described in claim 2 or 3, it is characterized in that the weight average molecular weight of described water soluble chitosan is no more than 5000Da.

5. according to the preparation method of single composite microcapsule that disperses capsule packing structure described in arbitrary claim in claims 1 to 3, its spy is in step (1), in injection-tube, First Transition pipe, the second transition conduit, the 3rd transition conduit, collecting pipe in the flow of oil phase, interior water, middle oil phase, outer water, outer oil phase be respectively 200～350 μ L/h, 400～600 μ L/h, 800～1200 μ L/h, 1600～2400 μ L/h, 4500～9000 μ L/h.

6. singly disperse according to claim 4 the preparation method of the composite microcapsule of capsule packing structure, its spy is in step (1), in injection-tube, First Transition pipe, the second transition conduit, the 3rd transition conduit, collecting pipe in the flow of oil phase, interior water, middle oil phase, outer water, outer oil phase be respectively 200～350 μ L/h, 400～600 μ L/h, 800～1200 μ L/h, 1600～2400 μ L/h, 4500～9000 μ L/h.

7. according to the preparation method of single composite microcapsule that disperses capsule packing structure described in arbitrary claim in claims 1 to 3, it is characterized in that described cleaning solvent is isopropyl alcohol or ethanol.

8. the preparation method who singly disperses according to claim 4 the composite microcapsule of capsule packing structure, is characterized in that described cleaning solvent is isopropyl alcohol or ethanol.

9. according to the preparation method of single composite microcapsule that disperses capsule packing structure described in arbitrary claim in claims 1 to 3, it is characterized in that interior oil phase or/and also contain oil-soluble active material in middle oil phase.

10. the preparation method who singly disperses according to claim 4 the composite microcapsule of capsule packing structure, is characterized in that interior oil phase or/and also contain oil-soluble active material in middle oil phase.