CN106267164A - Single dispersing insulin/chitosan gel rubber microsphere of size tunable and preparation method thereof - Google Patents
Single dispersing insulin/chitosan gel rubber microsphere of size tunable and preparation method thereof Download PDFInfo
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- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
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Abstract
Single dispersing insulin/chitosan gel rubber microsphere that the invention discloses a kind of size tunable and preparation method thereof, its step is as follows: preparation dispersion phase solution and continuous phase solution, control dispersion phase solution and the flow velocity of continuous phase solution and viscosity, after making dispersion phase solution and continuous phase solution converge in micro fluidic device, dispersion phase solution disperses in continuous phase solution, obtain the single dispersing insulin/chitosan emulsion droplet of size tunable, cured obtain single dispersing insulin/chitosan gel rubber microsphere.Single dispersing insulin/chitosan gel rubber microsphere surface form prepared by the present invention is preferable, uniform particle sizes, particle size range 50～600 μm, particle diameter breadth coefficient is less than 6%, carrying drug ratio 5%～30%, embedding rate 75%～85%, and there is insulin slow release performance, in the buffer solution that pH is 6.5～7.6, at 37 DEG C, 14h cumulative release rate is less than 60%.
Description
Technical field
The present invention relates to the preparation method of mono-dispersion microballoon, the single dispersing insulin/shell of size tunable gathers specifically
Sugar gel micro-ball and preparation method thereof.
Background technology
The choice drug insulin for the treatment of insulin dependent diabetes mellitus (IDDM), is mainly administered with injection form clinically, most
Patient needs frequent insulin injection (usual every day 1～4 times) all the life, with multiple untoward reaction: such as hypoglycemic reaction, pancreas
Island element edema, lipoatrophy, hypertrophy lipodystrophy, injection site inflammation, scleroma and drug resistance etc., carry to patient
Come inconvenience and great pain.
Mickel C etc. report, insulin active molecule can pass through intestinal wall absorbed into serum, and the absorbance of small intestinal is the highest, colon
Also higher absorbance is had with rectum.Bendayan M confirms that insulin molecule is to be transported into intestinal by intestinal epithelial cell
Interior environment, then infiltrate through capillary endothelial cell plasma membrane and enter blood circulation and play a role.
Carried medicine sustained-release microsphere is a kind of widely used Novel medicine feeding system, and it is with suitable macromolecular material for carrying
Body, by medicine dispersion or formation ball type carrier drug-supplying system embedded therein, particle diameter is one to hundreds of micron, can by oral,
The modes such as injection, suction enter internal.After using carried medicine sustained-release microsphere, internal active drug can be maintained in a long time dense
Degree, improves drug effect and reduces the untoward reaction of medicine, can improve the effectiveness of medication, safety, compliance, have important
Clinical value.
Chitosan is the adjuvant of a kind of good biocompatibility, low toxicity, is widely used in the various dosage forms of medicine.Valerie
D etc. study proof, and chitosan can open the compact siro spinning technology between gastrointestinal epithelial cells, thus promotes that protein and peptide drugs exists
Gastral absorption.Insulin is made sustained-release micro-spheres carry out enteric coating or load enteric coated capsule oral administration, can overcome
Insulin is difficult to overcome acid catalyzed decomposition, proteasome degradation and mucosa penetrance poor as protein absorption in gastrointestinal tract
Deng barrier, the low inferior shortcoming of bioavailability, patient can be overcome again to need frequent insulin injection to bring not all the life simultaneously
Just and produce multiple untoward reaction.
Traditional microsphere preparation technology is typically necessary and first passes through mechanical agitation or sonic oscillation obtains scattered emulsion droplet.
The mechanical external force so introduced is unstable, uneven (as distance mixing center or ultrasonic occurring source distance different parts are subject to
Power is different), thus cause drop size, emulsion droplet inner material content and the uneven concentration obtained, the medicine of final preparation carries
Body size heterogeneity, structural difference is big, bad dispersibility.And the Particle dispersity of pharmaceutical carrier and structure are to determine vitro Drug
The most important factor of release behavior.The size heterogeneity of pharmaceutical carrier will cause cannot accurately investigating medicine carrying microballoons amount and loading medicine
Thing amount, diameter of carrier and the relation of drug release, and targeting is poor, it is difficult to it is used safely in the treatment of clinical disease.
Owing to mechanical agitation or concussion have the strongest severity, often also result in the emulsion droplet collision of generation, crush so that it is
In drug diffusion go out and cause damage, thus the drug loading efficiency of the carrier of preparation is low, and biologically active drug also can be caused to lose
Live.And traditional stirring to prepare emulsion droplet process time-consumingly the longest, emulsion droplet cannot the most promptly be treated to the carrier of solidification, meeting
Make the sedimentation of the medicine in emulsion droplet or accumulate to emulsion droplet surface, causing carrier low to the envelop rate of medicine, at follow-up drug release
In show as phenomenon of burst release substantially and drug release be too fast, even do not reach the requirement of medicament slow release needed for clinical treatment.Separately
Outward, traditional preparation process is frequently used emulsifying agent, also can introduce more outside uncontrollable factor so that the medicine of preparation carries
Weight is uneven, preparation method poor reproducibility.
Microfluidic droplet technology is that droplet size is little at micro fluidic device upper-pilot very low volume fluids drop, it is easy to
Manipulation, is accurately controlled flow rate of liquid, it is ensured that the droplet size of preparation is homogeneous, composition is uniform, stable in properties.In micro-fluidic
The producing method that drop is gentle, the collision being reduced or avoided between drop crushes, and each drop is by another incompatible phase
Surrounding, drop does not contacts, it is to avoid the cross infection of sample room.And the stream of flow control body is raised at micro fluidic device
Speed, can regulate and control to generate the size of drop.Preparation required size, the list of uniform particle diameter can be regulated and controled hence with micro fluidic device
Dispersant liquid drop, resolidification becomes the monodispersed microsphere of target sizes, uniform particle diameter.
Summary of the invention
In order to solve the problems referred to above, the single dispersing insulin/shell that it is an object of the invention to provide a kind of size tunable gathers
The preparation method of sugar gel micro-ball.
Another object of the present invention is to provide the single dispersing insulin/chitosan gel rubber microsphere of a kind of size tunable.
In order to realize the purpose of the present invention, the single dispersing insulin/chitosan that the invention provides a kind of size tunable coagulates
The preparation method of glue microsphere, its step is as follows: preparation coagulation bath solution, dispersion phase solution and continuous phase solution, at micro-fluidic dress
Put middle control dispersion phase solution and the flow velocity of continuous phase solution and viscosity, after dispersion phase solution and continuous phase solution are converged, obtain
The insulin/chitosan solution drop of size uniformity, described drop by solidification obtain the single dispersing insulin of size tunable/
Chitosan gel rubber microsphere.
More specifically, the method comprises the following steps:
(1) preparation of coagulation bath solution: in proportion amine or amino alcohol are added mix homogeneously in alcohol, be configured to amine or amino
Alcohol percent by volume is the coagulation bath solution of 20%～55%；
(2) dispersion phase solution and the preparation of continuous phase solution: being added by chitosan containing percentage by weight is 0.5%～2%
Aqueous acetic acid in, add the insulin solutions that percentage by weight is 10%～30% that pH is 1.5～3.0, mixing is all
Even, as dispersion phase solution；Low polar compound is mixed with alcohol, prepare low polar compound and alcohol volume ratio be 100:(0～
250) continuous phase solution；
(3) dispersion phase and the flow velocity of continuous phase and viscosity are adjusted: adjusting dispersion phase flow velocity is 4～30 μ L min-1, continuously
Phase flow velocity is 50～300 μ L min-1, dispersed phase viscosity is 1～500mPa s, and continuous phase viscosity is 50～2500mPa s；
(4) formation of insulin/chitosan drop: step (2) gained dispersion phase solution and continuous phase solution are micro-fluidic
After device converges, the single dispersing insulin/chitosan solution drop of size tunable can be obtained；
(5) drop is solidified into microsphere: collect the drop of step (4) gained in the coagulation bath solution that step (1) prepares, liquid
Drip curable or semi-solid preparation, add aldehydes, gather in 25～60 DEG C of single dispersing insulin/shells being solidified into size tunable further
Sugar gel micro-ball.
Wherein, the alcohol described in step (1) is isoamyl alcohol, isooctanol or hexanol；Amine is triethylamine or trioctylamine；Amino alcohol is
Triethanolamine or diethanolamine.
Low polar compound described in step (2) is silicone oil, soybean oil or salad oil；Described alcohol is isoamyl alcohol, different
One or both in capryl alcohol or hexanol.
Aldehydes described in step (5) is low toxicity or nontoxic glutaraldehyde or vanillin, and the most nontoxic vanillin, because making
The vanillin that the insulin/chitosan gel rubber microsphere prepared with vanillin is degraded out is nontoxic, harmless.
Described preparation method also includes the post processing of step (6) insulin/aquagel microsphere: by step (5) institute
Insulin/chitosan gel rubber microsphere through filtration or decantation after, the organic solution organic solvent washing of residual, filter off molten
Agent, is vacuum dried 6～9h, obtains monodispersity insulin/chitosan gel rubber microsphere；Described organic solvent is hydrocarbon, halogenated hydrocarbons, alcohol
And one or more of ketone；Described hydrocarbon is pentane, hexane, petroleum ether；Halogenated hydrocarbons is dichloromethane, chloroform, four chlorinations
Carbon；Alcohol is methanol, ethanol, isopropanol；Ketone is acetone or butanone.
Invention further provides the single dispersing insulin/chitosan gel rubber of size tunable prepared by above-mentioned preparation method
Microsphere, the particle size range of described single dispersing insulin/chitosan gel rubber microsphere is 50～600 μm, and coefficient of dispersion CV is less than 6%；
Carrying drug ratio 5%～30%, embedding rate 75%～85%, and there is insulin slow release performance, molten in the buffering that pH is 6.5～7.6
In liquid, at 37 DEG C, 14h cumulative release rate is less than 60%.
The present invention utilizes single dispersing insulin/chitosan gel rubber microsphere surface form prepared by Microfluidic droplet technology relatively
Good, particle size range is 50～600 μm, and the vanillin degraded out especially with the microsphere that vanillin is prepared is harmless；Logical
Cross adjustment capillary diameter and dispersion phase solution and the flow velocity of continuous phase solution and viscosity, can be easily to prepared islets of langerhans
The size of element/chitosan gel rubber microsphere regulates and controls.
Accompanying drawing explanation
Fig. 1 is the elution profiles figure of the single dispersing insulin/chitosan microball of embodiment 1 preparation.
Fig. 2 is the elution profiles figure of the single dispersing insulin/chitosan microball of embodiment 2 preparation.
Fig. 3 is the elution profiles figure of the single dispersing insulin/chitosan microball of embodiment 3 preparation.
Fig. 4 is the elution profiles figure of the single dispersing insulin/chitosan microball of embodiment 4 preparation.
Fig. 5 is the schematic diagram of the micro fluidic device that the present invention uses.
Fig. 6 is the A portion enlarged drawing of Fig. 5.
In figure, the labelling of each parts is as follows: 1-1, dispersion phase syringe pump；1-2, continuous phase syringe pump；2-1, dispersion phase are injected
Device；2-2, continuous phase syringe；3, capillary tube.
Detailed description of the invention
Below in conjunction with specific embodiment, of the present invention related content is expanded on further.Only it is pointed out that these embodiments
For the present invention being described rather than limiting the scope of the present invention, and, after having read present disclosure, this area phase
Closing technical staff and the present invention can make various change or amendment, these equivalent form of values fall into right appended by the application equally and want
Seek book limited range.
Embodiment 1
The preparation method of the single dispersing insulin/chitosan gel rubber microsphere of size tunable, particularly as follows:
Being joined by 5mL triethanolamine in 16mL isooctanol, magnetic agitation mixes, and is configured to coagulation bath solution.
Chitosan is added and contains in the aqueous acetic acid that percentage by weight is 1%, be made into the shell that percentage by weight is 2.5%
Polysaccharide solution；Molten by weight adding, for 5:1, the percentage by weight 20% insulin hydrochloric acid that pH is 2.0 in chitosan solution again
Liquid, mix homogeneously, as dispersion phase solution；Isooctanol is mixed homogeneously with silicone oil 1:1 by volume, it is thus achieved that continuous phase solution.
Above-mentioned dispersion phase solution and continuous phase solution are respectively charged in syringe 2-1,2-2 of 10mL and 60mL, are placed in
On two syringe pumps 1-1,1-2, being connected in the micro fluidic device shown in Fig. 5 and Fig. 6, arranging dispersion phase flow velocity is 10 μ L
min-1, viscosity 200mPa s, continuous phase flow velocity is 100 μ L min-1, viscosity 560mPa s, capillary tube 3 in micro fluidic device
External diameter/internal diameter be 165/98 μm, open micro fluidic device, prepare the single dispersing insulin/chitosan solution liquid of size tunable
Drip；Insulin/chitosan solution drop that collection generates, in the culture dish equipped with above-mentioned coagulation bath solution, slowly stirs room temperature
After lower formation gel, add 0.2mL glutaraldehyde (25%) curing reaction 3.0h at 37 DEG C, drop can be solidified into insulin/
Chitosan gel rubber microsphere.After simple decantation, the organic solution petroleum ether of residual, chloroform respectively wash 2 times, then use ethanol
After washing 2 times, filter off ethanol, vacuum drying, obtain single dispersing insulin/chitosan gel rubber microsphere.
Insulin prepared by the present embodiment/chitosan gel rubber microsphere is nearly spheroidal, and there is slight gauffer on surface, and particle diameter is equal
One, there is monodispersity, particle diameter is 85 μm, carrying drug ratio 11%, embedding rate 76%, and microsphere delays at the mixed phosphate that pH is 6.86
In dissolved liquid, at 37 DEG C, sustained release performance is shown in Fig. 1.As seen from Figure 1, microsphere is prominent, and to release degree little, has slow release characteristic, and at 37 DEG C, 14h tires out
Long-pending medicine realeasing rate is less than 50%.
Embodiment 2
Being joined by 18mL triethylamine in 20mL isooctanol, magnetic agitation mixes, and is configured to coagulation bath solution.
Chitosan is added and contains in the aqueous acetic acid that percentage by weight is 1%, be made into the shell that percentage by weight is 2.5%
Polysaccharide solution；Molten by weight adding, for 5:1, the percentage by weight 20% insulin hydrochloric acid that pH is 2.0 in chitosan solution again
Liquid, mix homogeneously, as dispersion phase solution；Isooctanol is mixed homogeneously with silicone oil 1:1 by volume, it is thus achieved that continuous phase solution.
Above-mentioned dispersion phase solution and continuous phase solution are respectively charged in syringe 2-1,2-2 of 10mL and 60mL, are placed in
On two syringe pumps 1-1,1-2, being connected in the micro fluidic device shown in Fig. 5 and Fig. 6, arranging dispersion phase solution flow rate is 5 μ
L·min-1, viscosity 200mPa s, continuous phase solution flow velocity is 70 μ L min-1, viscosity 560mPa s, in micro fluidic device
External diameter/the internal diameter of capillary tube 3 is 165/98 μm, opens micro fluidic device, prepares single dispersing insulin/chitosan solution drop；
The drop that collection generates, in the culture dish equipped with above-mentioned coagulation bath solution, after slowly forming gel under stirring room temperature, adds
0.01g vanillin is curing reaction 1.5h at 60 DEG C, and drop can be solidified into insulin/chitosan gel rubber microsphere.Through simple
Decantation after, the organic solution petroleum ether of residual, chloroform respectively wash 2 times, then with after washing with alcohol 2 times, filter off ethanol, vacuum
It is dried, obtains single dispersing insulin/chitosan gel rubber microsphere.
Single dispersing insulin/chitosan gel rubber sustained-release micro-spheres prepared by the present embodiment is nearly spheroidal, and there is certain journey on surface
Degree gauffer, uniform particle diameter, there is monodispersity, particle diameter is 55 μm, carrying drug ratio 10%, embedding rate 75%, and microsphere is 7.2 at pH
In mixed phosphate salt buffer solution, at 37 DEG C, sustained release performance is shown in Fig. 2.From Figure 2 it can be seen that microsphere phenomenon of burst release is inconspicuous, there is slow release
Characteristic, at 37 DEG C, 14h cumulative release rate is less than 60%.
Embodiment 3
Being joined by 15mL triethylamine in 20mL isooctanol, magnetic agitation mixes, and is configured to coagulation bath solution.
Chitosan is added and contains in the aqueous acetic acid that percentage by weight is 1%, be made into the shell that percentage by weight is 2.5%
Polysaccharide solution；Molten by weight the percentage by weight 30% insulin hydrochloric acid adding pH=2.0 for 5:1 in chitosan solution again
Liquid, mix homogeneously, as dispersion phase solution；Isooctanol is mixed homogeneously with silicone oil 2:1 by volume, it is thus achieved that continuous phase solution.
Above-mentioned dispersion phase solution and continuous phase solution are respectively charged in syringe 2-1,2-2 of 10mL and 60mL, are placed in
On two syringe pumps 1-1,1-2, being connected in the micro fluidic device shown in Fig. 5 and Fig. 6, arranging dispersion phase flow velocity is 12 μ L
min-1, viscosity 270mPa s, continuous phase flow velocity is 100 μ L min-1, viscosity 420mPa s, capillary tube 3 in micro fluidic device
External diameter/internal diameter be 360/225 μm, open micro fluidic device, prepare single dispersing insulin/chitosan solution drop；Collect raw
The drop become, in the culture dish equipped with above-mentioned coagulation bath solution, after slowly forming gel under stirring room temperature, adds 0.01g Rhizoma et radix valerianae
Aldehyde is curing reaction 2.0h at 50 DEG C, and drop can be solidified into insulin/aquagel microballon.Through simple decantation
After, the organic solution petroleum ether of residual, chloroform respectively wash 2 times, then with after washing with alcohol 2 times, filter off ethanol, are vacuum dried,
Obtain single dispersing insulin/chitosan gel rubber sustained-release micro-spheres.
Single dispersing insulin/chitosan gel rubber sustained-release micro-spheres prepared by the present embodiment is elliposoidal, and particle diameter is 250 μm, table
There are to a certain degree gauffer, uniform particle diameter in face, has monodispersity.Microsphere carrying drug ratio 16%, embedding rate 82%, microsphere at pH is
In the mixed phosphate salt buffer solution of 6.5, at 37 DEG C, sustained release performance is shown in Fig. 3.As seen from Figure 3, microsphere is prominent releases lesser extent, has
Slow release characteristic, at 37 DEG C, 14h cumulative release rate is less than 50%.
Embodiment 4
Joining in 20mL isooctanol by 15mL triethylamine, 20mL dehydrated alcohol, magnetic agitation mixes, and is configured to coagulation bath
Solution.
Chitosan is added and contains in the aqueous acetic acid that percentage by weight is 1%, be made into the shell that percentage by weight is 2.5%
Polysaccharide solution；Molten by weight the percentage by weight 20% insulin hydrochloric acid adding pH=2.0 for 5:1 in chitosan solution again
Liquid, mix homogeneously, as dispersion phase solution；Isooctanol is mixed homogeneously with silicone oil 1:1 by volume, it is thus achieved that continuous phase solution.
Above-mentioned dispersion phase solution and continuous phase solution are respectively charged in syringe 2-1,2-2 of 10mL and 60mL, are placed in
On two syringe pumps 1-1,1-2, being connected in the micro fluidic device shown in Fig. 5 and Fig. 6, arranging dispersion phase flow velocity is 10 μ L
min-1, viscosity 250mPa s, continuous phase flow velocity is 100 μ L min-1, viscosity 560mPa s, capillary tube 3 in micro fluidic device
External diameter/internal diameter 245/98 μm, open micro fluidic device, prepare single dispersing insulin/chitosan solution drop；Collect generation
Drop, in the culture dish equipped with above-mentioned coagulation bath solution, is slowly formed after gel under stirring room temperature, add 0.01g vanillin in
Curing reaction 1.5h at 60 DEG C, drop can be solidified into insulin/aquagel microballon.After simple decantation, residual
The organic solution petroleum ether, the chloroform that stay respectively wash 2 times, then with after washing with alcohol 2 times, filter off ethanol, vacuum drying, obtain list
Dispersed islet cells element/chitosan gel rubber sustained-release micro-spheres.
Single dispersing insulin/chitosan gel rubber sustained-release micro-spheres prepared by the present embodiment is elliposoidal, and particle diameter is 95 μm, surface
There are to a certain degree gauffer, uniform particle diameter, there is monodispersity.Microsphere carrying drug ratio 11%, embedding rate 78%, microsphere is 7.6 at pH
Mixed phosphate salt buffer solution at 37 DEG C sustained release performance see Fig. 4.From fig. 4, it can be seen that microsphere phenomenon of burst release is inconspicuous, have slow
Releasing characteristic, at 37 DEG C, 14h cumulative release rate is less than 45%.
Claims (10)
1. the preparation method of the single dispersing insulin/chitosan gel rubber microsphere of a size tunable, it is characterised in that include following
Step:
(1) preparation of coagulation bath solution: in proportion amine or amino alcohol are added mix homogeneously in alcohol, be configured to amine or amino alcohol body
Long-pending percentage ratio is the coagulation bath solution of 20%～55%；
(2) dispersion phase solution and the preparation of continuous phase solution: chitosan is added containing the vinegar that percentage by weight is 0.5%～2%
In aqueous acid, add the insulin solutions that percentage by weight is 10%～30% that pH is 1.5～3.0, mix homogeneously, make
For dispersion phase solution；Being mixed with alcohol by low polar compound, preparing low polar compound with alcohol volume ratio is 100:(0～250)
Continuous phase solution；
(3) dispersion phase and the flow velocity of continuous phase and viscosity are adjusted: adjusting dispersion phase flow velocity is 4～30 μ L min-1, continuous phase stream
Speed is 50～300 μ L min-1, dispersed phase viscosity is 1～500mPa s, and continuous phase viscosity is 50～2500mPa s；
(4) formation of insulin/chitosan drop: step (2) gained dispersion phase solution and continuous phase solution are at micro fluidic device
In converge after, the single dispersing insulin/chitosan solution drop of size tunable can be obtained；
(5) drop is solidified into microsphere: the drop of collection step (4) gained is in the coagulation bath solution that step (1) prepares, and drop can
Solidification or semi-solid preparation, add aldehydes, coagulates in 25～60 DEG C of single dispersing insulin/chitosans being solidified into size tunable further
Glue microsphere.
2. preparation method as claimed in claim 1, it is characterised in that the alcohol described in step (1) is isoamyl alcohol, isooctanol or own
Alcohol；Amine is triethylamine or trioctylamine；Amino alcohol is triethanolamine or diethanolamine.
3. preparation method as claimed in claim 1, it is characterised in that the low polar compound described in step (2) be silicone oil,
Soybean oil or salad oil；Described alcohol is one or both in isoamyl alcohol, isooctanol or hexanol.
4. preparation method as claimed in claim 1, it is characterised in that the aldehydes described in step (5) is glutaraldehyde or vanillin.
5. preparation method as claimed in claim 4, it is characterised in that the aldehydes described in step (5) is vanillin.
6. preparation method as claimed in claim 1, it is characterised in that described preparation method also includes step (6) insulin/shell
The post processing of polysaccharide gel sustained-release micro-spheres: by the insulin of step (5) gained/chitosan gel rubber microsphere through filtering or decantation
After, the organic solution organic solvent washing of residual, filter off organic solvent, be vacuum dried 6～9h, obtain monodispersity islets of langerhans
Element/chitosan gel rubber microsphere.
7. preparation method as claimed in claim 6, it is characterised in that described organic solvent is the one of hydrocarbon, halogenated hydrocarbons, alcohol and ketone
Plant or several.
8. preparation method as claimed in claim 7, it is characterised in that described hydrocarbon is pentane, hexane, petroleum ether；Halogenated hydrocarbons
For dichloromethane, chloroform, carbon tetrachloride；Alcohol is methanol, ethanol, isopropanol；Ketone is acetone or butanone.
9. the single dispersing insulin/chitosan of size tunable prepared by the preparation method described in claim 1～8 any one coagulates
Glue microsphere.
10. single dispersing insulin/chitosan gel rubber microsphere as claimed in claim 9, it is characterised in that described single dispersing islets of langerhans
The particle size range of element/chitosan gel rubber microsphere is 50～600 μm, coefficient of dispersion CV be less than 6%, carrying drug ratio 5%～30%, embedding
Rate 75%～85%, and there is insulin slow release performance, 14h cumulative release at 37 DEG C in the buffer solution that pH is 6.5～7.6
Rate is less than 60%.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110280192A (en) * | 2019-07-10 | 2019-09-27 | 南京理工大学 | The preparation method of carbon nanotube-polyvinyl alcohol gel micro-ball |
| CN113617237A (en) * | 2021-08-10 | 2021-11-09 | 吉林大学 | Preparation method of oil-water emulsion with uniform and controllable particle size and stable system |
| CN115590200A (en) * | 2022-11-02 | 2023-01-13 | 北京逯博士行为医学科技研究院有限公司（Cn） | Effective component embedding method based on meal replacement powder |
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| CN1698900A (en) * | 2005-06-02 | 2005-11-23 | 中国科学院过程工程研究所 | Chitosan drug carrying microsphere with uniform size, high embedding rate and high drug activity maintaining rate and its preparation process |
| CN1843600A (en) * | 2006-03-28 | 2006-10-11 | 上海一鸣过滤技术有限公司 | Intensified microporous membrane of polyethersulfone and method for preparing the same |
| CN102068409A (en) * | 2011-01-13 | 2011-05-25 | 清华大学 | Method for preparing mono-disperse microemulsion, liposome and microsphere based on microfluidic technology |
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| 欧歌等: "采用离子交联法制备壳聚糖胰岛素纳米粒的研究进展", 《中南药学》 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110280192A (en) * | 2019-07-10 | 2019-09-27 | 南京理工大学 | The preparation method of carbon nanotube-polyvinyl alcohol gel micro-ball |
| CN110280192B (en) * | 2019-07-10 | 2022-05-20 | 南京理工大学 | Preparation method of carbon nano tube-polyvinyl alcohol gel microspheres |
| CN113617237A (en) * | 2021-08-10 | 2021-11-09 | 吉林大学 | Preparation method of oil-water emulsion with uniform and controllable particle size and stable system |
| CN115590200A (en) * | 2022-11-02 | 2023-01-13 | 北京逯博士行为医学科技研究院有限公司（Cn） | Effective component embedding method based on meal replacement powder |
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| CN106267164B (en) | 2019-11-26 |
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