CN101816913B - A kind of Microsphere manufacture method and manufacturing equipment - Google Patents
A kind of Microsphere manufacture method and manufacturing equipment Download PDFInfo
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- CN101816913B CN101816913B CN201010177862.3A CN201010177862A CN101816913B CN 101816913 B CN101816913 B CN 101816913B CN 201010177862 A CN201010177862 A CN 201010177862A CN 101816913 B CN101816913 B CN 101816913B
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- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- 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
The invention provides manufacture method and the manufacturing equipment of microballoon.This Microsphere manufacture method produces microballoon by present device in mode simple and continuously.In the method for producing microballoon, by the raw material supplying equipment of liquid form, form droplet through device processes, droplet runs in equipment, solidify to form microballoon gradually, by the mode of purge gas or liquid, collects microspheres product at equipment collector.
Description
Technical field:
The present invention relates to a kind of manufacture method and manufacturing equipment of microballoon.
Background technology:
A small entity spheric granules, its particle size range is generally 1-250 μm, is referred to as microballoon.Along with the development of pharmaceutical science, find to utilize some excellent characteristics of microballoon to reach target or slowly-releasing, the long-acting conveying effect of medicine.Namely microballoon can carry chemical small molecule medicine, can be used for again the macromolecular drugs such as transport proteins matter and polypeptide.The microballoon of these pastilles is called as medicine microspheres.Medicine microspheres can oral administration, or muscle, subcutaneous administrations.
Prepare medicine microspheres, the profile subglobular of General Requirements medicine microspheres, carrying drug ratio is higher, and entrapment efficiency is higher, and size controlling is in certain scope, and distribution is concentrated.Also need to prevent prominent releasing for slowly-releasing or depot drug product microballoon, rate of release is controlled.
As operable pharmaceutical preparation, need to reduce the irrelevant residue brought in preparation, such as organic solvent residual as far as possible.For some sensitive drug, such as much efficient and responsive peptide and protein medicine, also needs in the preparation process of medicine microspheres, use temperate condition to ensure the effective stability of medicine and activity as much as possible.
At present, the simple and reliable method for large-scale production medicine microspheres is few.
Common are following preparation methods (Cui Fude edits for " pharmacy " the 6th edition, People's Health Publisher).
" solvent-nonsolvent method ", its preparation process is generally as follows: in material solution, add a kind of solvent insoluble to material (non-solvent), cause and be separated, and is wrapped up by medicine, makes microballoon.Wherein need the solvent using a lot of toxicity, in the industrial-scale production of medicine microspheres, have no this method.
" intra-liquid desiccation method ", generally removes the solvent flashing in decentralized photo, prepares medicine-containing microsphere, be also called " emulsification-evaporation method " from emulsion.Many uses emulsification and a large amount of organic solvent, between batch, operation controls more difficult, this method rare in the industrial-scale production of medicine microspheres.
" spray drying process " is generally be dispersed in the solution of material by medicine, and this mixed liquor by little nozzle, sprays in high temperature gas flow, obtains medicine-containing microsphere by spray-on process after gases at high pressure are sheared.This method needs high temperature, and the profile of particle and domain size distribution are difficult to control, and are limited to the more special material of minority and prepare microballoon.The dry particle of the spray obtained by " spray drying process ", profile is mostly random, therefore, it is possible to adopt the application of this method production microspheres product few.
Also has the usage of some accommodations " spray drying process ", its preparation method is, first carrier material, medical surfaces activating agent, water, organic solvent etc. is made emulsion, then is entered by LS a large amount of by the ethanol ice of liquid nitrogen frozen, heat up removing organic liquor, obtains medicine microspheres.Its preparation process is more complicated, with high costs.
At present seen said method, generally needs to use exhibiting high surface activating agent or organic solvent, or the productive rate of product and envelop rate lower, or manufacturing condition is complicated, and industrial reproducibility and reliability is poor; With an organic solvent make protein and peptide inactivation in a large number in technique, and the difficult problem such as the dissolvent residual toxicity of product limits the industrial-scale production of medicine microspheres and extensively sends out application.At present, commercial scale is not applicable to carry out the physical mechanical of medicine microspheres production and corresponding production method.
Summary of the invention:
The problem that quasi-solution of the present invention is determined
Under such a condition, the object of this invention is to provide the method for producing microballoon.The method can by simple plant equipment, with continuously, can the raw microballoon of the mode of production of scale.The method can also be suitable for some microballoon preparation methods needing to avoid organic solvent and the leading emulsification of surfactant, but do not get rid of yet be suitable for by these solvents to prepare microballoon.Relatively low temperature conditions also can be provided and be applicable to preparation to the medicine microspheres of sensitive.Another object of the present invention is to provide the equipment producing microballoon.
The mode of dealing with problems
According to the present invention, provide by simple plant equipment, can continuously, the mode of production of scale produces medicine microspheres.
This mode according to plant equipment production microballoon provided by the invention can be described as, be dispersed into the mixed liquor of liquid raw material, be transported to by liquid feed device, the droplet generating means of equipment, mixed liquor is after droplet generating means, be highly dispersed in main cavity with the form of droplet, in the process that droplet runs in main cavity, gradually except desolventizing or condensation cured form microballoon product; Microballoon product is collected device and collects.
According to the present invention, provide the production equipment of microballoon, this equipment comprises:
For Primary containers device prepared by microballoon, the present invention is referred to as main cavity; The double-decker of main cavity wall preferably containing thermal insulation layer.
For mixed liquor being input to the liquid feed device of droplet generating means, this liquid feed device comprises at least one for nozzle for liquid, mixed liquor can be carried to droplet generating means through nozzle;
For mixed liquor being formed the device of droplet, this device at least comprises that be subject to driving can the video disc of High Rotation Speed, and drives the power set of video disc, can be high-speed motor;
For the air ring of the centripetal air blowing of video disc planar central to High Rotation Speed;
For the formation of the airflow apparatus of tangential whirlwind;
For collecting the device of microballoon, this device is made up of sample divider and multiple fan trays.
Invention effect
As described above, according to the present invention, mixed liquor is fed droplet generating means, and by the air-flow constrained operation in main cavity, form solid granulates gradually, particle enters gathering-device with air-flow and forms microballoon product.Thereby, it is possible to effectively produce microballoon in a straightforward manner.
Accompanying drawing is sketched
Fig. 1: the diagram of an embodiment of microsphere production equipment of the present invention.
Fig. 2: the annulus diagram that the airflow apparatus of the tangential whirlwind that an embodiment of microsphere production equipment of the present invention is used comprises.
Fig. 3: the diagram of the pallet that an embodiment of microsphere production equipment of the present invention collection microsphere unit used comprises.
Fig. 4: the displaing micro photo figure of the medicine microspheres that the embodiment of the present invention 1 is produced.
Fig. 5: the displaing micro photo figure of the medicine microspheres that the embodiment of the present invention 2 is produced.
Fig. 6: the displaing micro photo figure of the medicine microspheres that the embodiment of the present invention 3 is produced.
Fig. 7: the displaing micro photo figure of the medicine microspheres that the embodiment of the present invention 4 is produced.
Fig. 8: the displaing micro photo figure of the medicine microspheres that the embodiment of the present invention 5 is produced.
Fig. 9: the displaing micro photo figure of the medicine microspheres that the embodiment of the present invention 6 is produced.
Implement best mode of the present invention
According to the method for production microballoon of the present invention, the raw material mixed liquor of solution, microparticle suspending liquid, emulsion or fused solution form is fed droplet generating means.
In the preferred embodiment, mixed liquor comprises solvent, and is dissolved in wherein for the material of microballoon, and wherein solvent is water.
In the preferred embodiment, mixed liquor comprises solvent, and is dissolved in wherein for the material of microballoon, and wherein solvent can be organic solvent, such as ethanol.
In the preferred embodiment, mixed liquor can also be emulsion, and the material for microballoon is scattered in wherein, such as, is dissolved into by polypeptide drugs in water, is mixed to form emulsion with the material liquid being dissolved in carrene.
In the preferred embodiment, mixed liquor can also be microparticle suspending liquid, and for the material of microballoon, can be dispersed in wherein, suspended particle particle diameter is preferably less than less than 30 microns.Such as, medicine is dispersed in micronised ethylcellulose suspension.
In the preferred embodiment, for the material of microballoon, can also be the liquid melting shape, such as, drug powder is mixed in the wax oil of thawing, be formed and melt shape liquid.
According to the present invention, by liquid feed device, mixed liquor is input to droplet generating means.Specifically, this liquid feed device comprises at least one for nozzle for liquid, and can carry through nozzle and revolve on dish face belonging to mixed liquor to droplet generating means, the diameter of preferred nozzle is below 2mm; Nozzle not with revolve butterfly face and contact, preferred nozzle and video disc closely below 3mm.Mixed liquor adds to through nozzle and revolves on dish face, preferably with the form of continuous drop.
According to the present invention, mixed liquor forms droplet through the process of droplet generating means.This droplet generating means comprises circular disc, and the CD-ROM drive motor driving video disc to rotate.Specifically, mixed liquor is evenly added on the video disc of rotation, preferably the center of video disc, by the High Rotation Speed centrifugal action of rotating compact disc, mixed liquor disperses and runs to the edge of video disc on video disc, is subject to the effect of disc edge air-flow, form droplet, enter main cavity and run.The speed of service of preferred video disc is more than 2000 revs/min.
According to the present invention, the air ring device of centripetal air blowing provides centripetal air-flow, and preferred air ring is identical with the horizontal plane residing for video disc or more, and preferred distance is the rise lower than 10 centimetres; The temperature of air-flow and size can be controlled.Droplet is under the effect of centripetal air-flow, and droplet seldom flies on main cavity wall, remains in main cavity and runs.
According to the present invention, form the airflow apparatus of tangential whirlwind, the whirlwind being subject to size and controlling is provided, above-mentioned droplet can be provided at the power of main cavity continuous service.Tangential gas flow is not specifically limited at the number of inlets of main cavity wall, and being preferably number of inlets is four.Entry position, preferably at main cavity bottom position above water 5cm, is evenly arranged respectively.Under tangent line air flow inlet, also comprise an annulus, can mainly upwards run by controls local tangent line air-flow.Annulus can be multiple fan-shaped circular ring plate composition, its overall diameter should close to main cavity internal diameter, and anchor ring width is unrestricted, is preferably 10 centimetres.Annulus 9 placement location should lower than tangent line air flow inlet, and preferred difference in level should be less than 3 centimetres.
According to the present invention, preferably by three portion collection microballoon products.
Part I, comprises multiple fan trays composition, preferably position 12 as shown in Figure 1, and shown in Fig. 1-2.The quantity of pallet is not specifically limited, but need surround a full circle.Pallet is positioned over bottom main cavity, as shown in Figure 1 position 12, the passway 13 bottom the centripetal aligning main cavity of each pallet difference, position 13 as shown in Figure 1.Each fan trays all has a corresponding blow valve port, as shown in Figure 1 position 11, can the centripetal purge gas of parallel holding tray surface; Such as, or can depict particular of the present invention as, this blow valve port can purge out liquid as required, liquid nitrogen, or other treat liquid.
Part II, is made up of the first sample collection device.Preferred form as shown in Figure 1, comprises by gas channel 13, convolution sedimentation device 14, sample divider 15, and can be described to the liquid circulation channel outlet 22 of particular of the present invention use, and return 23 forms.
Part III, is made up of the second sample collection apparatus.Preferred form as shown in Figure 1, comprises by the passage be connected with 14, convolution sedimentation device 16, sample divider 17, and gas circulation adjuster 21 composition.
According to method of the present invention, in the ordinary course of things, can produce with the microspheres with solid of particle diameter between 1-250 μm.When raw material mixed liquor contains medicine, solid-state medicine microspheres can be obtained.Particular of the present invention can be depicted as, such as, at blow valve port (diagram 1-1 position 11) liquid purge or liquid nitrogen, can microsphere suspension liquid be obtained.
Embodiment
An embodiment of microsphere production equipment of the present invention is described below with reference to Fig. 1.
This equipment has for equipment body chamber 1, introduces the nozzle 3 of raw material mixed liquor, and the high-speed rotary dish 4 that the droplet generating means that raw material mixed liquor is become droplet 20 comprises; For the air ring device 5 of centripetal air blowing, this device can provide air-flow to the plate-spinning of High Rotation Speed, the scope that constraint droplet runs, and provides the gas of uniform temperature as required, evaporates, play the effect of initial concentration to solvent contained by droplet; Tangent line airflow apparatus 8, for generation of along main cavity inwall swirling eddy, can extend the range ability of droplet in cavity through initial concentration, further the solvent of removing contained by droplet, makes droplets solidify be the microballoon object of solid fraction; For the fan trays device 12 of auxiliary microballoon collection of products, and provide the blow valve port 11 being parallel to each holding tray surface purge gas, the microspheres with solid product that this device promotion part falls to pallet is centripetal to be concentrated; Microballoon product, through passway 13, enters the first sample collection device 15.
Be not specifically limited the type of nozzle 3, as long as mixed liquor uniform, controllable can be added to the center of high-speed rotary plate-spinning by this nozzle, preferred diameter is the atomizer of below 2mm.
At droplet generating means, by the dish 4 that revolves of High Rotation Speed, raw material mixed liquor is disperseed, form entering in main cavity of droplet and run.The rotating speed of plate-spinning does not limit, and preferred plate-spinning rotating speed is more than 2000 turns, is generally no more than 15000 turns, but does not limit this rotating speed upper limit.This device comprises, and raw material mixed liquor is separated into the plate-spinning 4 of droplet, for rotating disk provides the motor 6 of rotary power, and for the device 7 of air-breathing.Getter device is for removing the issuable a small amount of leakage of plate-spinning 4 or irregular material 19, and its bore is not restricted, and is preferably not more than and revolves dish diameter 2 centimetres, air entry varying height positions, and preferably its position plane is lower than revolving dish but being no more than 5 centimetres.
Through the droplet that droplet generating means produces, enter main cavity and run, the centripetal airflow function that the air ring device 5 being subject to centripetal air blowing produces.Device 5 can provide air-flow to rotation dish plane is centripetal, the scope that constraint droplet runs, and evaporates, play the effect of initial concentration to solvent contained by droplet.Droplet is under the effect of centripetal air-flow, and droplet seldom flies on main cavity wall, remains in main cavity and runs.This air ring setting position, preferably identical with the horizontal plane revolved residing for dish or more, preferably exceed and be highly no more than 10 centimetres; Air ring is connected with other external device, and this external device provides the air-flow of temperature and size-controlled system.
Droplet runs downwards gradually in main cavity, is subject to the effect of the swirling eddy that main cavity internal tangent air-stream generating device 8 produces, and range ability extends, and contained by droplet, solvent is removed, and forms solid shape microballoon.For generation of the tangent line air-stream generating device 8 along the tangential swirling eddy of main cavity, this device air flow inlet quantity is unrestricted, and preferably four entrances are evenly distributed on same level.The air flow direction of four entrances should be consistent, preferably consistent with the direction of rotation of plate-spinning 4.Tangent line air-stream generating device also comprises an annulus 9 (diagram 1-2), and also can be multiple fan-shaped circular ring plate compositions, its overall diameter should close to main cavity internal diameter, and anchor ring width is unrestricted, is preferably 10 centimetres.Annulus 9 placement location should lower than tangent line air flow inlet, and preferred difference in level should be less than 3 centimetres.
The solid shape microballoon formed runs to the bottom of main cavity gradually, and through passage 13, enter the first sample collection device 14, most of microspheres settle is in sample divider 15.
In the equipment of the present embodiment, mainly improve the collection efficiency of microballoon, be connected by passage with 14 as the second sample collection apparatus 16, collecting 15 does not have the part microballoon collected can obtain in sample divider 17.Wherein gas can by exhaust dispensing device 21, and control the distribution of air-flow, such as get rid of tolerance 50% turns back to purge gas passway 10 by adjusting device.
In the equipment of the present embodiment, as the fan trays 12 of assisted collection device, the part microballoon be deposited in bottom main cavity can be accepted.When each fan trays has a nozzle or liquid inlet 11, pallet highest point, under the horizontal plane of annulus 9, preferably should be less than 5 millimeters.
The particular implementation of the present embodiment can being described as, when taking gas purging mode, pumping into gas by 21 devices, now entrance 11 is gas nozzle, and each pallet has the purge gas purge pallet pumped into by passage 21, now by 22,23,24 fluid paths connected are in closed condition.
Another particular implementation of the present embodiment can be described as, when needs take liquid wash or process microballoon product, by the liquid inlet 24 of each pallet, by each for liquid wash pallet, and sample divider supernatant can return by interface channel mouth 22 and EGR 23, circulation flushing, when inputting starting liq, can be inputted by 22 or 23 access ports, not be restricted.When adopting liquid wash, the gas regulation of passage 21 does not pump into gas.
When first, second sample collection apparatus 16 provides enough microballoon collecting effects, more gathering-device need not be provided.In order to improve the collecting effect of microballoon further, can link together multiple with the second gathering-device.
Below by describing the equipment using above-mentioned embodiment, carry out the embodiment of microballoon production.
Embodiment 1
By 150 grams of Gelatin in 1000 ml waters of temperature about 60 degree, in stirring, add 10 grams of Doxycycline Hyclates, to dissolving completely.This pastille mixed liquor is prepared Doxycycline Hyclate medicine microspheres according to embodiment.Wherein in the pallet operation of assisted collection, adopt gas purging method.Collect microballoon at collector 15 and 17 place, produce the medicine microspheres of embodiment 1 thus.
Embodiment 2
100 grams of ethyl celluloses are dissolved in the ethanol of 1000 milliliter 82%, add paracetamol 15 grams.This pastille mixed liquor is prepared paracetamol medicine microspheres according to embodiment.Wherein in the pallet operation of assisted collection, adopt gas purging method.Collect microballoon at collector 15 and 17 place, produce the medicine microspheres of embodiment 2 thus.
Embodiment 3
40 grams of dextrans are dissolved in 250 ml waters, thymopeptide-5 1 gram is added in gentle agitation, by this aqueous solution under the mixing speed of minutes 400 turns, be evenly added in the dichloromethane solution of the poly lactic-co-glycolic acid of 300 milliliter 10%, form milky white shape emulsion.This pastille emulsion is prepared thymopeptide-5 medicine microspheres according to embodiment.Wherein in the pallet operation of assisted collection, adopt gas purging method.Collect microballoon at collector 15 and 17 place, produce the medicine microspheres of embodiment 3 thus.
Embodiment 4
By 120 grams of micronised ethylcellulose (domain size distribution is below 30 microns), be dispersed in the HPMC of 300 milliliter 5%, then metoprolol tartrate medicine 20 grams is dissolved in wherein, stir, obtain pastille suspension.This pastille emulsion is prepared metoprolol tartrate medicine microspheres according to embodiment.Wherein in the pallet operation of assisted collection, adopt gas purging method.Collect microballoon at collector 15 and 17 place, produce the medicine microspheres of embodiment 4 thus.
Embodiment 5
Get 100 grams of cetanols, heating and melting, add 5 grams of Risperidones, stir in this wax oil, the pastille obtaining Risperidone melts shape liquid.This pastille is melted shape liquid and prepares Risperidone medicine microspheres according to embodiment.Wherein in the pallet operation of assisted collection, adopt gas purging method.Collect microballoon at collector 15 and 17 place, produce the medicine microspheres of embodiment 5 thus.
Embodiment 6
12 grams of sodium alginates are dissolved in 200 ml waters, then add interferon 0.3 gram, stir gently and form interferon sodium alginate soln.The calcium dihydrogen phosphate aqueous solution of another preparation 3% 2000 milliliters, as liquid handling flushing liquor.Wherein in the pallet operation of assisted collection, adopt liquid wash method.Microsphere suspension liquid is collected, the gelatinous drug microballoon of centrifugal rear generation embodiment 6 at collector 15 place.
Testing example 1
1. the microballoon sample outward appearance of couple embodiment 1-6 is carried out microscopic observation and is taken pictures, and use instrument is come card microscope (LeicaDM5000B, Germany), adopts interference light source to take pictures.Fig. 4-9 shows.
Picture display adopts equipment provided by the invention and implementation method, and the sphericity of the medicine microspheres sample prepared in a continuous manner is good, dispersed excellent.
2. the microsphere sample of couple embodiment 1-6 carries out domain size distribution analysis, and instrument is MASTERSIZER 2000 (MALVERNINSTRUMENT).
Wherein to embodiment 1-5 sample, dry method is adopted to measure; Adopt wet method to measure to embodiment 6 sample, medium is the phosphate buffer of PH 5.0.
Droplet measurement the results are shown in Table 1.Result shows, and adopt equipment provided by the invention and implementation method, the centralized particle diameter of the medicine microspheres sample prepared in a continuous manner, uniformity is excellent.
Table 1
3. the microballoon sample of couple embodiment 1-6 carries out medicine assay.The results are shown in Table 2.
Entrapment efficiency (%)=mensuration microsphere drug content/medicine drops into content × 100%
Result shows, and adopt equipment provided by the invention and implementation method, the envelop rate of the medicine microspheres sample prepared in a continuous manner is all more than 95%.
The analytical method of each embodiment microballoon sample medicament contg is described below respectively:
Embodiment 1 sample, with reference to " Chinese Pharmacopoeia " 2010 editions two, Doxycycline Hyclate sheet measures containing method below quantifier.
Embodiment 2 sample, with reference to " Chinese Pharmacopoeia " 2010 editions two, paracetamol tablets measures containing method below quantifier.
Embodiment 3 sample, with reference to " national drug standards " WS1-(X-027)-2004Z, under thymopeptide-5 assay item, method measures.
Embodiment 4 sample, with reference to " Chinese Pharmacopoeia " 2010 editions two, tartaric acid acid metoprolol tablets measures containing method below quantifier.
Embodiment 5 sample, with reference to " national drug standards " WS1-(X-056)-2003Z, measures under Risperidone in Tablets assay item.
Embodiment 6 sample, first using gel micro-ball freeze-drying as sample, the accurate microballoon 10 milligrams taking drying during mensuration, add 10 milliliters, water concussion 3 times, each 3 minutes, 0.2 micron membrane filter filtered, and gets subsequent filtrate, measure at wavelength 280nm place with ultraviolet-visible spectrophotometer, the titer measured value prepared with raw material calculates content.
Table 2
Claims (6)
1. produce the method for microballoon, it is characterized in that the method is specially and the raw material mixed liquor of solution, microparticle suspending liquid, emulsion or fused solution form is fed droplet generating means; By droplet generating means, raw material mixed liquor is scattered in main cavity with the form of droplet; By the droplet that raw material mixed liquor height of formation disperses by the droplet generating means containing high-speed rotary plate-spinning; Droplet is subject to the constrained operation of centripetal air-flow and tangent line swirling eddy in main cavity; Gradually except desolventizing or condensation cured form microballoon product; Microballoon product is collected device and collects.
2. according to the method for the production microballoon of claim 1, it is characterized in that, wherein treat that the raw material of microballoon is the form of liquid.
3. according to the method for the production microballoon of claim 1, it is characterized in that, microballoon product is collected device and collects.
4. produce the equipment of microballoon, it is characterized in that this equipment comprises:
The Primary containers device prepared for microballoon contains thermal insulation layer and double-decker;
For mixed liquor being input to the confession nozzle for liquid of droplet generating means, through nozzle, raw material mixed liquor is transported to droplet generating means;
For raw material mixed liquor is formed the device of droplet, this device at least comprises that be subject to driving can the video disc of High Rotation Speed;
For the air ring of the centripetal air blowing of video disc planar central to High Rotation Speed;
For the formation of the airflow apparatus of tangential whirlwind;
For collecting the device of microballoon.
5. according to the equipment of the production microballoon of claim 4, it is characterized in that, for the formation of the airflow apparatus of tangential whirlwind, comprise the entrance that tangential gas flow is provided, and can the annulus that mainly upwards runs of controls local tangent line air-flow under tangent line air flow inlet.
6. according to the equipment of the production microballoon of claim 5, it is characterized in that, its device collecting microballoon product comprises,
Part I, multiple fan trays and blow valve port corresponding to each fan trays, blow valve port can the centripetal purge gas of parallel holding tray surface; Or liquid purge;
Part II, the first sample collection device, this device comprises gas channel, convolution sedimentation device, sample divider; Also comprising can by liquid-circulating to the lane device being back to blow valve port;
Part III, the second sample collection apparatus, this device comprises the passage be connected with the first sample, convolution sedimentation device, sample divider, and the adjuster device that gas can be circulated to blow valve port.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201010177862.3A CN101816913B (en) | 2010-05-20 | 2010-05-20 | A kind of Microsphere manufacture method and manufacturing equipment |
| PCT/CN2011/070790 WO2011143953A1 (en) | 2010-05-20 | 2011-01-29 | Method and apparatus for manufacturing microspheres |
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| CN201010177862.3A CN101816913B (en) | 2010-05-20 | 2010-05-20 | A kind of Microsphere manufacture method and manufacturing equipment |
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| CN101816913B true CN101816913B (en) | 2015-10-21 |
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| CN101816913B (en) * | 2010-05-20 | 2015-10-21 | 吴传斌 | A kind of Microsphere manufacture method and manufacturing equipment |
| CN102579365B (en) * | 2012-03-22 | 2014-06-11 | 中山大学 | Risperidone microsphere preparation and preparation method thereof |
| CN102579368B (en) * | 2012-03-28 | 2013-07-10 | 广州万泽医药科技有限公司 | Metoprolol slow-release microsphere, slow-release medical composition and preparation method of metoprolol slow-release microsphere |
| CN106511348B (en) * | 2016-11-02 | 2019-04-19 | 中山大学 | Huperzine skeleton particle, oral disintegrating tablet and preparation method thereof |
| CN106617094A (en) * | 2016-12-30 | 2017-05-10 | 广州新济药业科技有限公司 | Probiotics microcapsule as well as preparation method and application thereof |
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| CN109806242B (en) * | 2019-01-31 | 2021-02-12 | 浙江圣兆药物科技股份有限公司 | Risperidone microsphere preparation and preparation method thereof |
| KR102283250B1 (en) * | 2020-12-24 | 2021-07-29 | (주)인벤티지랩 | Solvent removing apparatus and method of manufacturing microsphere using the same |
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| CN1871007A (en) * | 2003-10-23 | 2006-11-29 | 布里斯托尔-迈尔斯.斯奎布公司 | Process for making sterile aripiprazole of desired mean particle size |
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| US7258873B2 (en) * | 2002-04-11 | 2007-08-21 | Medimmune Vaccines, Inc. | Preservation of bioactive materials by spray drying |
| US20040154985A1 (en) * | 2003-02-07 | 2004-08-12 | Ferro Corporation | Method and apparatus for producing particles via supercritical fluid processing |
| US20070122488A1 (en) * | 2004-02-25 | 2007-05-31 | Erich Windhab | Multi-functional microcapsules and method and device for manufacturing same |
| AU2006222667A1 (en) * | 2004-02-25 | 2006-10-19 | Eidgenossische Technische Hochschule Zurich | Storage-Stable Multimicrocapsules Having Adjustably Synergistic Functional Ingredients and Method and Device for Making the Same |
| ATE342338T1 (en) * | 2004-06-04 | 2006-11-15 | Procter & Gamble | ENCAPSULATED PARTICLES |
| JP5054570B2 (en) * | 2007-05-10 | 2012-10-24 | 株式会社リコー | Powder, method for producing electrophotographic toner, and electrophotographic toner |
| CN101357310B (en) * | 2008-09-02 | 2011-09-21 | 浙江大学 | Device for preparing particulates using supercritical fluid assistant spray and use thereof |
| CN101816913B (en) * | 2010-05-20 | 2015-10-21 | 吴传斌 | A kind of Microsphere manufacture method and manufacturing equipment |
-
2010
- 2010-05-20 CN CN201010177862.3A patent/CN101816913B/en active Active
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2011
- 2011-01-29 WO PCT/CN2011/070790 patent/WO2011143953A1/en active Application Filing
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1218394A (en) * | 1996-05-08 | 1999-06-02 | 吸入治疗系统 | Dispersible macromolecule compositions and methods for their preparation and use |
| US6343602B1 (en) * | 1999-04-16 | 2002-02-05 | Gsf Forshungszentrum Fur Umwelt Und Ges | Method of and a device for dry application of substances on inhalable pulverulent carrier substances |
| CN1871007A (en) * | 2003-10-23 | 2006-11-29 | 布里斯托尔-迈尔斯.斯奎布公司 | Process for making sterile aripiprazole of desired mean particle size |
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| CN101816913A (en) | 2010-09-01 |
| WO2011143953A1 (en) | 2011-11-24 |
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