CN203042961U

CN203042961U - Device continuously producing microspheres

Info

Publication number: CN203042961U
Application number: CN 201320007335
Authority: CN
Inventors: 孙考祥; 姚东刚; 王涛; 粱荣才; 刘万卉; 张晓喜
Original assignee: Shandong Luye Pharmaceutical Co Ltd
Current assignee: Shandong Luye Pharmaceutical Co Ltd
Priority date: 2012-01-10
Filing date: 2013-01-08
Publication date: 2013-07-10
Anticipated expiration: 2023-01-08
Also published as: CN103191021A

Abstract

The utility model provides a novel process device preparing microsphere preparation. The device comprises an oil phase liquid storage pot (1), a water phase liquid storage pot (2), seal pipelines (4), a static mixer (5) and a continuous emulsifying device (6), wherein the oil phase liquid storage pot (1) and the water phase liquid storage pot (2) are respectively connected with the static mixer (5) through the seal pipelines (4), and the static mixer (5) is then in seal connection with the continuous emulsifying device (6) in series. According to the device, influence on the grain diameters of the microsphers from flowing speed during a microsphere manufacturing process is reduced, product yield loss is reduced, material transfer procedures are reduced, processing time is reduced, and production cost is reduced.

Description

A kind of equipment of continuous production microsphere

Technical field

This utility model relates to a kind of equipment for preparing microball preparation, is specifically related to reduce flow velocity in the microsphere process to the influence of microspherulite diameter a kind of the preparation, and reduces the product yield loss, reduces the equipment of material transfer step.

Background technology

In recent decades, slow release microphere for injection obtains extensive use at field of medicaments, this type of preparation is skeleton with the macromolecular material of different degradation cycles, by preparation process bioactive ingredients (chemical compound of therapeutical effect, vaccine etc.) is dispersed in the skeleton, usually form the microgranule of 5-250 μ m spheroids or globoid, said preparation can obtain the therapeutic effect that single administration namely has several weeks even some months by the selection of macromolecular material, obviously improves patient's compliance.It is bigger that the drug release behavior of sustained-release micro-spheres is influenced by particle diameter and particle size distribution, and medicine release in vivo has crucial effects to therapeutic effect, therefore must strict control microspherulite diameter and distribution thereof on commercial production.

Prepare slow release microphere for injection the method for normal employing be emulsifying-solvent evaporation method, this method generally adopts in the retort of batch processing intermittently emulsifying device is installed, or singly realizes with equipment such as static mixer, continuous emulsification equipment.

Installing intermittently in the retort of employing batch processing, the mode of emulsifying device prepares slow release microphere for injection, generally, material (oil phase) is sheared probability in disperse medium (water) lower, prepared microspherulite diameter distribution is wide, add material simultaneously earlier and add the difference of material on homogenizing time with the back, also can cause prepared microspherulite diameter to differ greatly; Distribution just because of the microspherulite diameter for preparing is wide, in actual production process, further takes the mode of two layer screen to control the particle diameter of holding back microsphere usually; Because this method self and need repeatedly sample transfer operation in the process of sieving makes the yield of microsphere that this method is produced that decline significantly be arranged.In addition, adopt batch process to produce sustained-release micro-spheres, from the bench scale to the pilot scale and (or) jumbo variations such as production scale equipment size, shape, all cause the lab scale technological parameter can be poor with reference to property in the product amplification process, increase unpredictability.

Single mode with static mixer obtains sustained-release micro-spheres, exist microsphere parameter (particle diameter etc.) to the flow velocity sensitive issue, the biphase overall flow rate of oil phase, aqueous phase flow rate and profit is all to particle diameter and the generation considerable influence that distributes thereof, except the control complexity, the lab scale technological parameter is amplified to pilot scale or production scale, flow velocitys etc. certainly will change, and this gropes pilot scale or production-scale parameter is disadvantageous.

Single experimental results show that with continuous emulsification equipment (as pipeline high-shear emulsifying homogeneous dispersion machine) owing to there is not good premix process, the microspherulite diameter distribution of producing is wideer, simultaneously the flow velocity of two phase liquid is to particle diameter and distribute and also can produce considerable influence during access arrangement, and the lab scale technological parameter directly is amplified to pilot scale or production scale can't realize.

Thereby wish that a kind of microsphere production equipment can be arranged, and reduce the biphase overall flow rate of oil phase, aqueous phase flow rate and profit as far as possible to the influence of microspherulite diameter, improve yield simultaneously, reduce the sample transfer operation, and can realize continuously big commercial production.

Summary of the invention

The inventor is through further investigation, adopt a kind of equipment of continuous production microsphere to solve the problems of the technologies described above, equipment comprises oil phase fluid reservoir 1, water fluid reservoir 2, closed conduit 4, static mixer 5 and continuous emulsification device 6, oil phase fluid reservoir 1, water fluid reservoir 2 are connected by closed conduit 4 with static mixer 5 respectively, and static mixer 5 is connected with continuous emulsification equipment 6 series seals again; The closed conduit that preferably enters static mixer 5 is equipped with sterile filtering device 8.

Described continuous emulsification device 6 can be pipeline high-shear emulsifying homogeneous dispersion machine, and pipeline high-shear emulsifying homogeneous dispersion machine comprises casing, body, at least one group " stator-rotor set ", and rotor is designed to the antithesis interlock, the flute profile dense arrangement; Equipment preferably is equipped with chiller, specifically can be cooling-water duct, and cooling-water duct is arranged in the interlayer of casing and body, or independent coiling is arranged on outside the casing.It is SV type, SX type, SL type, SK type, SH type or JHF type that static mixer 5 arranges model.

Pipeline high cut disperse emulsification homogenizer is to rotate stably by rotor high-speed, forms comprehensive kinetic energy effects such as high frequency, strong tangent to periphery speed, angle speed; Under the effect of stator, stator and rotor rationally form comprehensive effects such as strong, reciprocal fluid power shearing, friction, centrifugal extruding, liquid stream collision in the narrow gap, material is back and forth handled or the online disposable above work process of finishing dealing with in the container outer circulation, finally make immiscible or difficult mix two-phase or multiphase finish technical processs such as dispersion, emulsifying, homogenizing, dissolving rapid, even, fine and smoothly.

Temperature when this utility model chiller mixes in order to reduce; make secondary mixing, the employed equipment of high strength shear stage have good cooling effect; formed the good environment of low-temperature mixed; the thermally labile medicine is played a very good protection, created necessary condition for quick cooling emulsion after the emulsifying simultaneously.

Preferred oil phase fluid reservoir 1 connects closed conduit and enters in the static mixer 5 by elbow 9, reduces biphasely when just mixing, and flow velocity and pressure is to mixing the influence of rendeing a service, and mixes more evenly, has guaranteed stablizing of product quality.

It is also two dosing pumps 3 to be set by oil phase fluid reservoir 1, water fluid reservoir 2 respectively by closed conduit 4 to be connected with static mixer 5 that concrete equipment constitutes, dosing pump 3 is used for accurately control oil, biphase ratio and the flow velocity of water, under the driving force of dosing pump 3, oil, water is biphase goes into static blender 5 from port flow; Under the effect of the mixing original paper through being fixed on static mixer 5 tube wall inside, oil phase tentatively disperses at aqueous phase, and then flows into the continuous emulsification equipment 6 of connecting, at short notice can further uniform treatment.

Equipment provided by the utility model has following advantage: the mode that 1, adopts static mixer series connection continuous emulsification equipment, with respect to using intermittently emulsifying device or single with traditional approachs such as static mixers, the suffered shearing force of material is more even, and material disperses more abundant.2, the microsphere span that adopts this utility model equipment to produce is littler, more even; 3, the particle diameter of microsphere and span are not subjected to the viscosity of macromolecular material and the influence of water oil phase flow velocity substantially; 4, microsphere in earlier stage prominent release little, discharge steadily, the middle and late stage medicine discharges gradually, the whole cycle evenly discharges; 5, all devices is common apparatus, and the integral device floor space is little, and small investment is suitable for large-scale production.

Description of drawings

Fig. 1 equipment sketch map of the present utility model

Fig. 2 oil phase elbow enters the static mixer sketch map

Marginal data: 1. oil phase fluid reservoir 2. water fluid reservoirs 3. dosing pumps 4. closed conduits 5. static mixers 6. continuous emulsification equipment 7. collecting tanks 8. sterile filtering devices 9. elbows

The specific embodiment

Below with reference to specific embodiment and Figure of description this utility model is described in further details.

As shown in Figure 1, the equipment of continuous production microsphere of the present utility model, equipment comprises static mixer 5 and continuous emulsification device 6, and oil phase fluid reservoir 1, water fluid reservoir 2 are connected by closed conduit 4 with static mixer 5 respectively, and static mixer 5 is connected with continuous emulsification equipment 6 series seals again; The closed conduit that enters static mixer 5 is equipped with sterile filtering device 8.

The operation principle of the sterile filling transfusion system of automatic control feed liquor of the present utility model is as follows: oil phase fluid reservoir 1, water fluid reservoir 2 also arrange two dosing pumps 3 respectively by closed conduit 4 and are connected with static mixer 5, dosing pump 3 is used for accurately control oil, biphase ratio and the flow velocity of water, under the driving force of dosing pump 3, oil phase, water are by sterile filtering device 8 aseptic process, the closed conduit of oil phase 1 connection enters in the static mixer 5 by elbow 9 then, and water is gone into static blender 5 from port flow simultaneously; Under the effect of the mixing original paper through being fixed on static mixer 5 tube wall inside, oil phase tentatively disperses at aqueous phase, and then flows into the continuous emulsification equipment 6 of connecting, at short notice can further uniform treatment.

Above embodiment only is used for illustrating this utility model, and is not that this utility model is had any restriction effect, as long as in the claimed scope of essence of the present utility model, variation, the modification of the above embodiment is all belonged to protection domain of the present utility model.

Claims

1. equipment of producing continuously microsphere, it is characterized in that equipment comprises oil phase fluid reservoir (1), water fluid reservoir (2), closed conduit (4), static mixer (5) and continuous emulsification device (6), oil phase fluid reservoir (1), water fluid reservoir (2) are connected by closed conduit (4) with static mixer (5) respectively, and static mixer (5) is connected with continuous emulsification equipment (6) series seal then.

2. equipment according to claim 1, the closed conduit (4) that it is characterized in that entering static mixer (5) is equipped with sterile filtering device (8).

3. equipment according to claim 1 is characterized in that continuous emulsification equipment (6) is pipeline high-shear emulsifying homogeneous dispersion machine.

4. equipment according to claim 3 is characterized in that the pipeline high-shear emulsifying homogeneous dispersion machine that uses in the equipment comprises casing, body, at least one group " stator-rotor set ".

5. according to the arbitrary described equipment of claim 1-4, it is characterized in that being equipped with in the equipment chiller, chiller is arranged in the interlayer of casing and body, or independent coiling is arranged on outside the casing.

6. according to the described equipment of claim 5, it is characterized in that chiller is cooling-water duct in the equipment.

7. equipment according to claim 6 is characterized in that static mixer (5) is set to SV type, SX type, SL type, SK type, SH type or JHF type.

8. equipment according to claim 7 is characterized in that the oil phase fluid reservoir connects closed conduit and enters in the static mixer by elbow (9).

9. according to the arbitrary described equipment of claim 1-4, it is characterized in that static mixer (5) is set to SV type, SX type, SL type, SK type, SH type or JHF type.

10. according to the arbitrary described equipment of claim 1-4, it is characterized in that the oil phase fluid reservoir connects closed conduit and enters in the static mixer by elbow (9).