CN106074448A - A kind of eccentric microsphere application in medicine ultrasonically controlled-release - Google Patents
A kind of eccentric microsphere application in medicine ultrasonically controlled-release Download PDFInfo
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- CN106074448A CN106074448A CN201610654388.6A CN201610654388A CN106074448A CN 106074448 A CN106074448 A CN 106074448A CN 201610654388 A CN201610654388 A CN 201610654388A CN 106074448 A CN106074448 A CN 106074448A
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- 239000004005 microsphere Substances 0.000 title claims abstract description 71
- 239000003814 drug Substances 0.000 title claims abstract description 51
- 238000013270 controlled release Methods 0.000 title claims abstract description 24
- 229940079593 drug Drugs 0.000 claims abstract description 16
- 238000002360 preparation method Methods 0.000 claims abstract description 9
- 238000000034 method Methods 0.000 claims description 11
- 239000004205 dimethyl polysiloxane Substances 0.000 claims description 10
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 claims description 10
- 239000000463 material Substances 0.000 claims description 7
- 239000007864 aqueous solution Substances 0.000 claims description 6
- 230000001804 emulsifying effect Effects 0.000 claims description 5
- -1 polydimethylsiloxane Polymers 0.000 claims description 5
- 239000004094 surface-active agent Substances 0.000 claims description 5
- 230000009471 action Effects 0.000 claims description 3
- 239000007795 chemical reaction product Substances 0.000 claims description 3
- 229920002521 macromolecule Polymers 0.000 claims description 3
- 238000004132 cross linking Methods 0.000 claims description 2
- 102000004169 proteins and genes Human genes 0.000 claims description 2
- 108090000623 proteins and genes Proteins 0.000 claims description 2
- 230000000694 effects Effects 0.000 abstract description 6
- 238000001647 drug administration Methods 0.000 abstract description 3
- 230000003902 lesion Effects 0.000 abstract description 3
- 230000008685 targeting Effects 0.000 abstract description 3
- 235000013870 dimethyl polysiloxane Nutrition 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 230000006872 improvement Effects 0.000 description 7
- 239000000243 solution Substances 0.000 description 6
- 239000012530 fluid Substances 0.000 description 5
- CXQXSVUQTKDNFP-UHFFFAOYSA-N octamethyltrisiloxane Chemical compound C[Si](C)(C)O[Si](C)(C)O[Si](C)(C)C CXQXSVUQTKDNFP-UHFFFAOYSA-N 0.000 description 5
- 238000004987 plasma desorption mass spectroscopy Methods 0.000 description 5
- 238000002604 ultrasonography Methods 0.000 description 5
- VYXSBFYARXAAKO-WTKGSRSZSA-N chembl402140 Chemical compound Cl.C1=2C=C(C)C(NCC)=CC=2OC2=C\C(=N/CC)C(C)=CC2=C1C1=CC=CC=C1C(=O)OCC VYXSBFYARXAAKO-WTKGSRSZSA-N 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- 239000004372 Polyvinyl alcohol Substances 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 230000002708 enhancing effect Effects 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 238000005297 material degradation process Methods 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 229920002451 polyvinyl alcohol Polymers 0.000 description 2
- 229920000915 polyvinyl chloride Polymers 0.000 description 2
- 239000004800 polyvinyl chloride Substances 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000004088 simulation Methods 0.000 description 2
- 238000007711 solidification Methods 0.000 description 2
- 230000008023 solidification Effects 0.000 description 2
- 241000208340 Araliaceae Species 0.000 description 1
- 235000005035 Panax pseudoginseng ssp. pseudoginseng Nutrition 0.000 description 1
- 235000003140 Panax quinquefolius Nutrition 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 238000000862 absorption spectrum Methods 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000013267 controlled drug release Methods 0.000 description 1
- 238000001723 curing Methods 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 102000038379 digestive enzymes Human genes 0.000 description 1
- 108091007734 digestive enzymes Proteins 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 229920006332 epoxy adhesive Polymers 0.000 description 1
- 235000008434 ginseng Nutrition 0.000 description 1
- 238000013007 heat curing Methods 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 239000000693 micelle Substances 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 239000002077 nanosphere Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 230000032696 parturition Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 238000000016 photochemical curing Methods 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- PYWVYCXTNDRMGF-UHFFFAOYSA-N rhodamine B Chemical compound [Cl-].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=CC=C1C(O)=O PYWVYCXTNDRMGF-UHFFFAOYSA-N 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 238000002525 ultrasonication Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5031—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poly(lactide-co-glycolide)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5052—Proteins, e.g. albumin
Landscapes
- Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention provides a kind of eccentric microsphere application in medicine ultrasonically controlled-release, described eccentric microsphere includes shell and inner core, the center of the eccentric microsphere of inner core position deviation, forms thin-walled in eccentric microsphere side.The invention have the advantages that 1. have different resonance modes due to eccentric microsphere, it is possible to use resonance effect is precisely controlled slowly release to eccentric microsphere supported interior medicine or quickly discharges；2., due to the resonance effect of eccentric microsphere, make the release efficiency of medicine in eccentric microsphere higher, higher drug valid density can be maintained, improve utilization ratio of drug；3. preparation method is simple, accurate positioning, and stability is strong, is suitable for clinical practice；4. can maintain lesions position medicine effective concentration in a long time, need not again frequent drug administration simultaneously, be the means of a kind of preferable real-time controlled targeting loading.
Description
Technical field
The present invention relates to medicine ultrasonically controlled-release field, particularly to a kind of eccentric microsphere answering in medicine ultrasonically controlled-release
With.
Background technology
The treatment of most of diseases is all to be realized by Drug therapy, therefore can maintain lesions position medicine in a long time
Thing valid density, the medicine sustained and controlled release system that simultaneously need not again frequent drug administration just seems extremely important.According to drug release
Mechanism, the control delivery mode of medicine is broadly divided into material degradation and controls releasing mechanism and dispersal events mechanism, material degradation control
The influence factor of system release has and just has whether to there is the micro-chemical environment such as digestive enzyme, temperature and pH relevant；Dispersal events mechanism is
One physical process, it is mainly the most relevant with the stimulation of external environment, and such as electromagnetism, ultrasonic and light etc. can accelerate the speed of dispersal events
Degree.Ultrasound wave is the sound wave that frequency is higher than 20000 hertz, its good directionality, and penetration capacity is strong, and acoustic energy is easily concentrated.Therefore giving birth to
Thing engineering in medicine field, ultrasonically controlled-release is considered as the means of a kind of preferable real-time controlled targeting loading.It is without to patient
Carry out surgery formula operation, only need to reach Drug controlled release by parameters such as the supersonic frequency of accurate regulation and control applying or intensity
Purpose.In nowadays research, the pharmaceutical carrier of ultrasonic mediation mainly has liposome, micelle, a microvesicle etc., but these carriers
Stability still have problems, and the most most of carrier is all irreversible to ultrasonic response forms, is extremely difficult to
The effect of slow controlled release, location control accuracy is the highest simultaneously；In terms of controlling release, the regulation and control ginseng used in current research
Number is all ultrasound intensity mostly, but the focusing ultrasound wave of high intensity exists infringement to human body, limits the use of ultrasonically controlled-release
Scope.
Summary of the invention
In order to solve the deficiency of existing system, create a kind of stable, controlled, and can accurate Drug controlled release speed
Ultrasonic medicinal carrier and controlled release method, the invention provides a kind of eccentric microsphere application in medicine ultrasonically controlled-release.
As a further improvement on the present invention, described eccentric microsphere includes shell and inner core；The deviation of inner core position is eccentric micro-
The center of ball, forms thin-walled in eccentric microsphere side；Described walled thickness is in 10 nm to 10 μm.
As a further improvement on the present invention, the making material of described shell is biocompatibility macromolecule, described biology
Compatible polymer is polydimethylsiloxane or crosslinking protein.
As a further improvement on the present invention, described shell is different from the density of inner core.
As a further improvement on the present invention, the preparation method of described eccentric microsphere, comprise the following steps:
The most first sheathing material, pharmaceutical aqueous solution and surfactant are configured；
S2. sheathing material, pharmaceutical aqueous solution and surfactant that S1 obtains are made initially by emulsifying or micro emulsifying method
Medicine carrying microballoons；
S3. the initial medicine carrying microballoons that S2 obtains stood and solidifies, obtaining end product bias microsphere.
The present invention utilizes shell different from inner core density, by being stood for a long time by microsphere so that microsphere internal phase is at weight
There is significantly to deviate the center of eccentric microsphere under force field, eventually pass solidification fixing eccentric structure acquisition end-product inclined
Heart microsphere, described curing mode can be heat cure, photocuring and high molecular crosslink, and the method is applicable to multiple microcapsule preparation side
Method is to obtain eccentric structure.
As a further improvement on the present invention, to obtain core deviation according to time of repose difference eccentric micro-for described eccentric microsphere
The eccentric microsphere that ball center's degree is different.
As a further improvement on the present invention, described eccentric microsphere medicine under the ultrasonic action of different frequency, in core
The speed that thing outwards discharges is different.
The eccentric microsphere of the present invention has different resonance mode, and every kind of resonance mode has vibration mode and the resonance of self
Frequency.Amplitude enhancing amount distribution on eccentric microsphere when vibration mode refers mainly to occur to resonate；Resonant frequency refers to eccentric microsphere
Frequency during resonance is there is under each resonance mode.
The present invention utilizes multiple physical field modeling and simulation software COMSOL Multiphysics, to eccentric microsphere mode of resonance
State is simulated, and obtains multiple resonance mode and its corresponding resonant frequency.
The present invention, by applying the ultrasonic action of different frequency to eccentric microsphere, makes eccentric microsphere resonate, and allows bias
Microsphere is in certain a resonance mode, accelerates the internal phase medicine speed to external diffusion.
The present invention proposes eccentric nanosphere medicine carrier and has different resonance mode, by applying the ultrasound wave of characteristic frequency
Accelerate drug release and Drug controlled release.
The present invention is to provide for a kind of to be precisely controlled drug release rate according to the concrete needs of the state of an illness
Topical remedy's controlled release system.
The invention have the advantages that
1. due to eccentric microsphere, there is different resonance modes, it is possible to use eccentric microsphere supported interior medicine is carried out by resonance effect
It is precisely controlled slowly release or quickly discharges；
2., due to the resonance effect of eccentric microsphere, make the release efficiency of medicine in eccentric microsphere higher, higher drug can be maintained
Valid density, improves utilization ratio of drug.
3. preparation method is simple, accurate positioning, and stability is strong, is suitable for clinical practice.
4. can maintain lesions position medicine effective concentration in a long time, need not again frequent drug administration simultaneously, be a kind of
The means of preferable real-time controlled targeting loading.
Accompanying drawing explanation
The preparation process schematic diagram of eccentric microsphere in Fig. 1 present invention；
Fig. 2 is the longitudinal profile scanning electron microscope (SEM) photograph of embodiment 1；
Fig. 3 is the simulation drawing of the different resonance modes of embodiment 1；
Fig. 4 is the drug release patterns figure under the different supersonic frequency effects of embodiment 2.
Detailed description of the invention
Further describe the present invention below in conjunction with Figure of description and specific embodiment, but embodiment is not to this
Bright limit in any form.Unless stated otherwise, the present invention uses reagent, equipment and method are the art routine city
Reagent, equipment and the conventional use of method purchased.
Embodiment 1 preparation has the polydimethylsiloxane bias microsphere of different resonance mode
Accompanying drawing 1 is the preparation process schematic diagram of eccentric microsphere in the present invention, and the emulsifying method for preparing microsphere used by embodiment 1 is
Microfluidic control is for method, and three-phase fluid used controls equipment composition and mainly includes two polyvinyl chloride pipes and two capillary glass tubies
This device, by assembling to polyvinyl chloride pipe insertion syringe needle and capillary glass tube, reaches fixing formation with epoxy adhesive whole
Body device.
The concrete preparation flow of polydimethylsiloxane bias microsphere, comprises the following steps:
S1. configuration microsphere sheathing material: the polydimethylsiloxane (PDMS, composition A, B mixing, A:B=1:10) in mixing is used
Dchloromethane, dilution mass ratio is PDMS:DCM=3:1, and mix homogeneously bubble of going out are standby；
S2. pharmaceutical aqueous solution is configured: using rhodamine 6G aqueous solution to serve as aids drug, its concentration is 0.02 mg/mL；
S3. configuration surface activating agent: surfactant uses polyvinyl alcohol water solution, and its mass concentration is 2%；
S4. prepare medicine carrying bias microsphere: utilize three-phase fluid equipment to prepare medicine carrying microballoons according to necessarily arranging, stand remove dilute
Release agent and solidify, it is thus achieved that final products bias microsphere.
The concrete operations of step S4 are:
S41. PDMS with the DCM mixture of step S1 gained is connected with three-phase fluid equipment mesophase port, by step S2 institute
The rhodamine 6G solution obtained is connected to port, by the polyvinyl alcohol water solution three-phase flow of step S3 gained with in three-phase fluid equipment
Body equipment foreign minister's port connects, by three-phase fluid equipment, in, foreign minister's flow velocity keep fixing flow velocity (0.011 mL/ respectively
Min, 0.03 mL/min, 1.5 mL/min), prepare initial medicine carrying PDMS microsphere；
S42. the eccentric microsphere obtained is stood at 60 DEG C holding 30 min, it is thus achieved that remove the medicine carrying of diluent
Microsphere；
S43., after the microsphere removing diluent being stood solidification 30 min at 90 DEG C, after cleaning with pure water, final products are obtained
Medicine carrying PDMS bias microsphere.
Accompanying drawing 2 is the longitudinal profile scanning electron microscope (SEM) photograph of eccentric microsphere.
Accompanying drawing 3 is that the bias utilizing multiple physical field modeling and simulation software COMSOL Multiphysics simulation to obtain is micro-
3 kinds of resonance modes of ball, wherein the resonance amplitude enhancing of the 2nd rank resonance mode concentrates on eccentric microsphere thin-walled one end, its resonance
Frequency is 20.1 KHz.
Embodiment 2 eccentric microsphere drug release under identical ultrasound intensity, different supersonic frequencies
Its detailed process is as follows:
S1. the eccentric microsphere subpackage taking equivalent enters in 3 identical serum bottle, adds equivalent pure water, covers tightly lid and confirm
Seal；
S2. prepare 3 identical tanks, fill water and maintain water temperature at 37 DEG C；
S3. the serum being filled with eccentric microsphere by 3 is separately fixed at below each tank water surface 2.5 cm same position；
S4. 3 ultrasonicator horn are separately fixed at directly over serum bottle, below the water surface at 0.5 cm, probe ultrasonic
Frequency is respectively 20 KHz, 25 KHz and 33 KHz；
S5. keep identical fixing ultrasonic output, respectively eccentric microsphere is carried out ultrasonic, after the most ultrasonic 5 min, to serum
Solution in Ping carries out uv-visible absorption spectra mensuration, is the optical absorption peak value at 527 nm according to rhodamine 6G at wavelength
Determine rhodamine 6G concentration in solution, until ultrasonic full 60 min, it is thus achieved that the solution rhodamine concentration of 3 groups of 12 time points；
S6. Origin software is utilized to carry out arranging and plot analysis by 3 groups of data.
Accompanying drawing 4 is eccentric microsphere at constant power but drug release patterns figure under the ultrasonication of different frequency.
Above example only introduces the preferred case of the present invention, to those skilled in the art, without departing substantially from this
Any obvious changes and improvements carried out in the range of spirit, within being regarded as the scope of the present invention.
Claims (9)
1. the eccentric microsphere application in medicine ultrasonically controlled-release.
2. eccentric microsphere application in medicine ultrasonically controlled-release as claimed in claim 1, it is characterised in that described eccentric microsphere
Including shell and inner core；The center of the eccentric microsphere of inner core position deviation, forms thin-walled in eccentric microsphere side.
3. eccentric microsphere application in medicine ultrasonically controlled-release as claimed in claim 2, it is characterised in that described walled thickness
In 10 nm to 10 μm.
4. eccentric microsphere application in medicine ultrasonically controlled-release as claimed in claim 1, it is characterised in that the system of described shell
It is biocompatibility macromolecule as material.
5. eccentric microsphere application in medicine ultrasonically controlled-release as claimed in claim 4, it is characterised in that described bio-compatible
Property macromolecule is polydimethylsiloxane or crosslinking protein.
6. eccentric microsphere application in medicine ultrasonically controlled-release as claimed in claim 1, it is characterised in that described shell is with interior
Core density is different.
7. eccentric microsphere application in medicine ultrasonically controlled-release as claimed in claim 1, it is characterised in that described eccentric microsphere
Preparation method, comprise the following steps:
S1. sheathing material, pharmaceutical aqueous solution and surfactant are configured；
S2. sheathing material, pharmaceutical aqueous solution and surfactant that S1 obtains are made initially by emulsifying or micro emulsifying method
Medicine carrying microballoons；
S3. the initial medicine carrying microballoons that S2 obtains stood and solidifies, obtaining end product bias microsphere.
8. eccentric microsphere application in medicine ultrasonically controlled-release as claimed in claim 1, it is characterised in that described eccentric microsphere
The eccentric microsphere that core deviation eccentric microsphere center degree is different is obtained according to time of repose difference.
9. eccentric microsphere application in medicine ultrasonically controlled-release as claimed in claim 1, it is characterised in that described eccentric microsphere
Under the ultrasonic action of different frequency, the speed that the medicine in core outwards discharges is different.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610654388.6A CN106074448B (en) | 2016-08-11 | 2016-08-11 | A kind of application of the bias microballoon in drug ultrasonically controlled-release |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610654388.6A CN106074448B (en) | 2016-08-11 | 2016-08-11 | A kind of application of the bias microballoon in drug ultrasonically controlled-release |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN106074448A true CN106074448A (en) | 2016-11-09 |
| CN106074448B CN106074448B (en) | 2019-10-15 |
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20090297567A1 (en) * | 1998-02-06 | 2009-12-03 | University Of Pittsburgh - Of The Commonwealth System Of Higher Education | Method For Ultrasound Triggered Drug Delivery Using Hollow Microbubbles With Controlled Fragility |
| CN101653420A (en) * | 2009-09-08 | 2010-02-24 | 中国科学院化学研究所 | Ultrasonically controlled-release target medicinal preparation and production method thereof |
| CN101857699A (en) * | 2010-06-17 | 2010-10-13 | 西北工业大学 | Method for preparing organic-inorganic composite microspheres with eccentric structure |
| CN102249245A (en) * | 2011-04-28 | 2011-11-23 | 华南理工大学 | Single-hole silicon dioxide hollow microsphere and preparation method thereof |
-
2016
- 2016-08-11 CN CN201610654388.6A patent/CN106074448B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20090297567A1 (en) * | 1998-02-06 | 2009-12-03 | University Of Pittsburgh - Of The Commonwealth System Of Higher Education | Method For Ultrasound Triggered Drug Delivery Using Hollow Microbubbles With Controlled Fragility |
| CN101653420A (en) * | 2009-09-08 | 2010-02-24 | 中国科学院化学研究所 | Ultrasonically controlled-release target medicinal preparation and production method thereof |
| CN101857699A (en) * | 2010-06-17 | 2010-10-13 | 西北工业大学 | Method for preparing organic-inorganic composite microspheres with eccentric structure |
| CN102249245A (en) * | 2011-04-28 | 2011-11-23 | 华南理工大学 | Single-hole silicon dioxide hollow microsphere and preparation method thereof |
Non-Patent Citations (2)
| Title |
|---|
| MARJA SAVOLAINEN等: "Evaluation of controlled-release polar lipid microparticles", 《INTERNATIONAL JOURNAL OF PHARMACEUTICS》 * |
| 袁晓明: "PLGA-PEG 多孔载药微球的制备及超声波对其释药行为的影响研究", 《中国药房》 * |
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