CN117619242A

CN117619242A - Microsphere preparation feeding assembly, homogenizer and microsphere preparation method

Info

Publication number: CN117619242A
Application number: CN202311593239.XA
Authority: CN
Inventors: 卫书达; 周涓; 雷磊; 王丹; 李常辉; 金凯明; 周映聪
Original assignee: Kedi Biomedical Wuxi Co ltd
Current assignee: Kedi Biomedical Wuxi Co ltd
Priority date: 2023-11-27
Filing date: 2023-11-27
Publication date: 2024-03-01

Abstract

The invention discloses a microsphere preparation feeding assembly, a homogenizer and a microsphere preparation method. The microsphere preparation feed assembly includes an aqueous phase feed tube and an oil phase feed tube. The water phase feeding pipe comprises a feeding end pipeline and a discharging end pipeline which are connected with each other, and a water phase feeding channel is formed inside the water phase feeding pipe. The feeding end pipeline extends along a direction which is inclined and far away from the discharging end pipeline, and an included angle between the feeding end pipeline and the axis of the discharging end pipeline is an obtuse angle. Air or bubbles in the aqueous phase passing through the connection part between the feed end pipeline and the discharge end pipeline can be discharged along the aqueous phase feed channel. The outer wall portion of the end portion of the feeding end pipeline, which is close to one side of the discharging end pipeline, is provided with a connecting port, the oil phase feeding pipe stretches into the water phase feeding channel through the connecting port, and one end of the oil phase feeding pipe, which stretches into the water phase feeding channel, stretches out of the other end of the discharging end pipeline, which is far away from the feeding end pipeline.

Description

Microsphere preparation feeding assembly, homogenizer and microsphere preparation method

Technical Field

The invention relates to the technical field of homogenizing equipment, in particular to a microsphere preparation feeding assembly, a homogenizer and a microsphere preparation method.

Background

There are various ways of preparing microspheres, such as emulsion-solvent evaporation, phase separation, spray drying, membrane emulsification, etc., and in view of production cost, production batch, process maturity, etc., the mass production process in factories is currently mainly emulsion-solvent evaporation. The emulsification process is realized in a homogenizer, and the oil-water phase forms tiny emulsion drops under the action of high-speed shearing, and is commonly used in-tank shearing and on-line homogenization. When the shearing in the tank is amplified, the size change of the tank, the homogenizing cutter head and the stirring head is large, so that the homogenizing process needs to be fuelled again, and linear amplification is difficult to realize. The on-line homogenization can realize continuous high-speed shearing, namely continuous feeding and continuous discharging, the production efficiency is high, and compared with in-tank homogenization, the on-line homogenization is easier to realize linear amplification from pilot scale to production. However, the on-line homogenizer commonly used at present still has the dead volume of feed piece structure (the volume that is filled by aqueous phase oil phase in the homogeneity intracavity) and so on problem, and dead volume is too big and needs more material to fill the cavity volume, leads to the raw materials extravagant, and is more necessary to some expensive raw materials, reduction dead volume. Meanwhile, the dead volume is too large, so that the time for evacuating the air in the cavity is prolonged, the hollow emulsion drops are generated due to insufficient air evacuation, and the problem that water phase flows backward into the oil phase (when the viscosity of the oil phase is lower, the water phase is easier to occur) at the oil phase feed port in the process of forming the oil-in-water emulsion to form a water-in-oil structure and re-emulsion is generated after homogenization even though the air evacuation is sufficient and the design of the feed port is unreasonable is emphasized. The compound emulsion is easy to form hollow spheres after being subjected to subsequent processes such as solidification, washing, screening, freeze-drying and the like, and is broken to form fragments, so that the quality of microsphere products is unstable, and more serious, the fragments are irregular in shape and can cause needle blockage during injection, and the safety problems such as nodules and the like are easy to occur after injection.

Therefore, the problem that the quality of the microsphere product is unstable because hollow spheres are easy to form and broken into fragments when an online homogenizer is adopted to prepare the microsphere in the prior art exists.

Disclosure of Invention

The invention aims to solve the problems that in the prior art, when an online homogenizer is adopted to prepare microspheres, hollow spheres are easy to form and are broken to form fragments, so that the quality of microsphere products is unstable.

In order to solve the technical problems, the embodiment of the invention provides a microsphere preparation feeding assembly, which comprises a water phase feeding pipe and an oil phase feeding pipe.

The water phase feeding pipe comprises a feeding end pipeline and a discharging end pipeline which are connected with each other, the corresponding ends of the feeding end pipeline and the discharging end pipeline are connected with each other, and a water phase feeding channel with the same inner diameter and penetrating through the feeding end pipeline and the discharging end pipeline is formed inside the water phase feeding pipe. Wherein, the feed end pipeline extends along the direction of keeping away from for the slope of discharge end pipeline and sets up, and the axis contained angle of feed end pipeline and discharge end pipeline is the obtuse angle. And air or bubbles in the water phase at the mutually connected parts of the feeding end pipeline and the discharging end pipeline can be discharged along the water phase feeding channel.

One end of the oil phase feeding pipe extends into the water phase feeding channel, and the axis of the oil phase feeding pipe is parallel to the axis of the discharge end pipeline; and, the outer wall portion that the feed end pipeline is close to discharge end pipeline one side tip is provided with the connection port, and the oil phase inlet pipe stretches into aqueous phase feed channel through the connection port, and oil phase inlet pipe and connection port detachably fixed connection to the oil phase inlet pipe stretches into the one end of aqueous phase feed channel and stretches out the other end that the discharge end pipeline kept away from the feed end pipeline.

By adopting the technical scheme, the application discloses a microsphere preparation feeding assembly, including the water phase inlet pipe that advances the water phase alone respectively and the oil phase inlet pipe that advances the oil phase alone. The water phase inlet pipe comprises feed end pipeline and discharge end pipeline to the feed end pipeline extends the setting along the direction of keeping away from for the slope of discharge end pipeline, has such structure, when having air or bubble in the water phase inlet pipe, because there is pressure differential between feed end and the discharge end, more be favorable to air or bubble to discharge, thereby furthest reduces air or bubble in the water phase inlet pipe, avoids appearing air or bubble unable discharge and stays the condition in the homogenizer, further avoids appearing hollow emulsion condition after the homogeneity. Therefore, the microsphere preparation feeding assembly provided by the application can enable the microsphere appearance to be smoother and more round when feeding to prepare the microsphere, and no hollow microsphere and microsphere fragments appear. And the structure of unique water phase inlet pipe can realize automatic exhaust, and it is more swift convenient to exhaust.

Further, one end of the oil phase feeding pipe stretches into the other end of the water phase feeding channel, which extends out of the discharging end pipeline and is far away from the feeding end pipeline, namely, in the vertical direction, the discharging port of the oil phase feeding pipe is located below the water phase feeding pipe, and the oil phase feeding pipe is set to be a small-caliber inner diameter, the small-caliber design can prevent water phase from flowing backwards into the oil phase, if the water phase flows backwards into the oil phase, water-in-oil emulsion can be generated in the oil phase feeding pipe, and finally, the water-in-oil emulsion and the water phase form water-in-oil-in-water multiple emulsion in the homogenizing process. The water-in-oil-in-water compound emulsion can form hollow spheres after solidification, the hollow sphere solution is crushed to form fragments, and hollow microspheres or microsphere fragments can be prevented from being generated by the design of the oil phase feeding pipe, so that the preparation of high-quality and high-specification microspheres is ensured.

The embodiment of the invention also provides a microsphere preparation feeding assembly, wherein the feeding end pipeline and the discharging end pipeline are both cylindrical pipelines. And the included angle between the axes of the feeding end pipeline and the discharging end pipeline is 100-140 degrees.

By adopting the technical scheme, when the included angle between the axes of the feeding end pipeline and the discharging end pipeline is within the range of 100-140 degrees, air or bubbles in the water phase feeding pipe can be timely and rapidly discharged, and meanwhile, the effective working length of the feeding end pipeline and the discharging end pipeline can be reduced, so that the structure is simpler, and materials and cost are saved.

The embodiment of the invention also provides a microsphere preparation feeding assembly, and the inner diameter of the water phase feeding channel is in the range of 10-30 mm.

The oil phase feeding pipe comprises a plurality of replaceable oil phase feeding pipes, and the inner diameters of the plurality of replaceable oil phase feeding pipes are in the range of 0.5 mm-5 mm.

By adopting the technical scheme, the oil phase feeding pipe is arranged into a plurality of replaceable oil phase feeding pipes, the inner diameters of the plurality of replaceable oil phase feeding pipes are different, the replaceable oil phase feeding pipes with different inner diameters can be selected according to the requirements such as the viscosity and the feeding speed of the used oil phase, the oil phase feeding pipe is convenient to use and can meet larger application scenes, and the oil phase feeding pipe is arranged into the inner diameter with a small caliber.

The embodiment of the invention also provides a microsphere preparation feeding assembly, wherein the connecting port protrudes out of the outer wall part of the feeding end pipeline, the connecting port and the corresponding outer wall part of the feeding end pipeline are provided with through holes for the feeding pipe of the oil supply phase to pass through, and the inner wall part of the connecting port is provided with a connecting part.

The outer wall portion of the oil phase feeding pipe is provided with a connected portion which is matched with the connecting portion and detachably connected with the connecting portion, and a sealing portion is further arranged below the connected portion and is in sealing connection with the inner wall portion of the through hole.

By adopting the technical scheme, the through hole of the oil phase feeding pipe penetrating through the connecting port is detachably connected with the connecting port, oil phase pipes with different inner diameters can be conveniently replaced by the structure, and the sealing part is in sealing connection with the inner wall part of the through hole, so that the tightness of the end parts of the oil phase feeding pipe and the water phase feeding pipe connected is ensured.

The embodiment of the invention also provides a microsphere preparation feeding assembly, wherein the connecting part comprises a threaded connecting section and a pipeline connecting section, the threaded connecting section is provided with internal threads, the pipeline connecting section is provided with a smooth inner wall surface, and the pipeline connecting section is positioned at one side of the threaded connecting section, which is closer to a pipeline at the discharge end.

The connected part comprises an outer wall threaded connection section and a sealing member positioned at one side of the outer wall threaded connection section, the outer wall threaded connection section is detachably and adaptively connected with the threaded connection section, and the sealing member is in interference fit with the inner wall surface of the pipeline connection section. And in the axial direction of the oil phase feeding pipe, the axial extension length of the outer wall threaded connection section is larger than that of the threaded connection section.

By adopting the technical scheme, the connecting part and the connected part are arranged to be mutually matched with each other and are of an internal thread and external thread structure, so that the replacement and the disassembly are more convenient, and the sealing member is arranged to improve the sealing performance. And the axial extension length of the outer wall threaded connection section on the oil phase feeding pipe is greater than that of the threaded connection section, and through the design of the structure, the height of the oil phase feeding pipe can be adjusted according to requirements.

The embodiment of the invention also provides a microsphere preparation feeding assembly, and the inner wall surface of the corresponding end part of the connection between the feeding end pipeline and the discharging end pipeline is smooth curved.

By adopting the technical scheme, when the inner wall of the corresponding end part of the connection between the feeding end pipeline and the discharging end pipeline is in a gentle curved surface shape, the water phase can be prevented from generating bubbles or air when flowing in the water phase feeding pipe, and the flowing is stable, so that the quality of formed microspheres is improved.

The embodiment of the invention also provides a homogenizer, comprising the microsphere preparation feeding assembly of any one of the above, and further comprising:

the homogenizer body comprises a homogenizer feed inlet and a homogenizer discharge outlet, the homogenizer feed inlet is detachably connected with a discharge end pipeline of the water phase feeding pipe in a sealing mode, the homogenizer discharge outlet is arranged on one side of the homogenizer body, a homogenizing cavity is formed in the homogenizer body, and the homogenizer feed inlet and the homogenizer discharge outlet are respectively communicated with the homogenizing cavity. Wherein the homogenizing cavity is communicated with the water phase feeding channel in the discharge end pipeline, the corresponding end part of the oil phase feeding pipe extends out of the water phase feeding channel, and the oil phase feeding pipe is communicated with the homogenizing cavity. And the axial direction of the discharge port of the homogenizer is perpendicular to the axial direction of the feed port of the homogenizer.

By adopting the technical scheme, the water phase and the oil phase can enter the homogenizing cavity through the feeding port of the homogenizer for homogenizing, and because of the design of the oil phase feeding pipe and the water phase feeding pipe in the application, air or bubbles do not enter the homogenizing cavity, and double emulsion drops of water-in-oil, water-in-oil-in-water and the like can not be formed. Therefore, the microspheres with uniform size and smooth outer wall can be formed, hollow microspheres, microsphere fragments and the like can not be generated, and the quality of the prepared microspheres is improved.

The embodiment of the invention also provides a microsphere preparation method, which is used for the homogenizer and comprises the following steps:

the oil phase is prepared from polymer and dichloromethane, the mass ratio of the polymer to the dichloromethane is 1:X, and the oil phase with the concentration of 1/(1+X) percent is prepared after stirring and dissolving.

Preparing a water phase, wherein the water phase is prepared from a surfactant and pure water, the mass ratio of the surfactant to the pure water is 1:Y, and stirring and dissolving the mixture at the reaction temperature of 20-99 ℃ to obtain the water phase with the concentration of 1/(1+Y)%.

The oil phase after preparation is pumped into the homogenizer by an oil phase feeding pipe, the water phase is pumped into the homogenizer by a feeding end pipeline of a water phase feeding pipe, and the mass ratio of the oil phase to the water phase is 1:Z.

The oil phase and the water phase enter a homogenizer, and after 10-30 seconds from the beginning of homogenization, the sample is taken from a discharge port of the homogenizer to obtain emulsion.

And (3) an emulsion curing step, namely pouring the emulsion into curing water, wherein the mass ratio of the emulsion to the curing water is 1:alpha, and stirring and curing the mixed solution of the emulsion and the curing water for 2-4 hours to obtain the preliminarily cured microsphere.

And (3) cleaning the microspheres, namely removing redundant water phase on the surfaces of the microspheres through cleaning liquid after the primary solidification is finished and the microspheres are obtained.

And freeze-drying the microspheres, namely freeze-drying the microspheres collected after the step of washing the microspheres by using a freeze dryer.

Wherein, the X value is in the range of 4-19, the Y value is in the range of 19-199, the Z value is in the range of 5-15, the alpha value is in the range of 5-20, the X, Y, Z value and the alpha value are proportional multiple values, and are not actual values.

By adopting the technical scheme, after the microspheres collected after the step of cleaning the microspheres are freeze-dried by using the freeze dryer, the sizes of the obtained microspheres are uniform, the outer walls of the microspheres are smooth, the quality of the microspheres is high, and impurities such as hollow microspheres and microsphere fragments are not generated.

The embodiment of the invention also provides a microsphere preparation method, wherein the polymer can be any one of polycaprolactone, polylactic acid and polylactic acid-glycolic acid copolymer, and the aqueous phase preparation liquid comprises polyvinyl alcohol.

The beneficial effects of the invention are as follows:

the invention discloses a microsphere preparation feeding assembly, a homogenizer and a microsphere preparation method. The microsphere preparation feed assembly includes aqueous phase inlet pipe and oil phase inlet pipe, the aqueous phase inlet pipe includes feed end pipeline and the discharge end pipeline that meet each other, the feed end pipeline extends along the orientation of keeping away from for the slope of discharge end pipeline and sets up, and the axis contained angle of feed end pipeline and discharge end pipeline is the obtuse angle, when having air or bubble in the aqueous phase inlet pipe, air or bubble will be discharged along the feed end pipeline, and because there is pressure differential between feed end and the discharge end, more be favorable to air or bubble to discharge, thereby furthest reduces air or bubble in the aqueous phase inlet pipe, avoid appearing air or bubble unable to get rid of the condition that gets into the homogenizer, further avoid appearing after the homogeneity condition such as hollow breast drop. Therefore, the microsphere preparation feeding assembly provided by the application can enable the microsphere appearance to be smoother and more round when feeding to prepare the microsphere, and no hollow microsphere and microsphere fragments appear. The discharge gate of oil phase inlet pipe is located the below of water phase inlet pipe to, set up the oil phase inlet pipe to the internal diameter of small-bore, this small-bore design can avoid the water phase to flow backward into the oil phase, avoids hollow microsphere or microsphere piece to produce, can also select the interchangeable oil phase inlet pipe of different internal diameters according to the viscosity of used oil phase and demand such as feed rate, convenient to use just can satisfy bigger application scenario. The homogenizer comprises a microsphere preparation feeding component, the size of the microspheres prepared by the homogenizer and the microsphere preparation method is uniform, the outer wall of the microspheres is smooth, the quality of the microspheres is high, and hollow microspheres, microsphere fragments and other impurities are not generated.

Drawings

FIG. 1 is a schematic diagram of a microsphere preparation feed assembly according to an embodiment of the present invention;

FIG. 2 is a cross-sectional view of a microsphere preparation feed assembly provided in an embodiment of the present invention;

FIG. 3 is a cross-sectional view of a microsphere preparation feed assembly according to an embodiment of the present invention taken along the axis of an oil phase feed pipe;

FIG. 4 is a cross-sectional view of a water phase feed tube in a microsphere preparation feed assembly according to an embodiment of the present invention;

FIG. 5 is a view of an alternative orientation of a water phase feed tube in a microsphere preparation feed assembly according to an embodiment of the present invention;

FIG. 6 is a schematic diagram of an oil phase feed tube in a microsphere preparation feed assembly according to an embodiment of the present invention;

FIG. 7 is a schematic diagram of a homogenizer and a microsphere preparation feed assembly according to an embodiment of the present invention;

FIG. 8 is an optical microscope view of emulsion droplets obtained from a control example provided in example 4 of the present invention using microspheres of the present application to prepare a feed assembly;

FIG. 9 is a scanning electron microscope view of microspheres obtained by using the microspheres of the present application to prepare a feed assembly in a comparative example provided in example 4 of the present invention;

FIG. 10 is a schematic illustration of a homogenizer self-contained microsphere preparation feed assembly in a comparative example provided in example 4 of the present invention;

FIG. 11 is a cross-sectional view of a homogenizer self-contained microsphere preparation feed assembly in a comparative example provided in example 4 of the present invention;

FIG. 12 is an optical microscope view of emulsion droplets obtained from a control example provided in example 4 of the present invention using a homogenizer to prepare a feed assembly from microspheres;

FIG. 13 is a scanning electron microscope view of microspheres obtained by preparing a feed assembly from microspheres carried by a homogenizer in a comparative example provided in example 4 of the present invention;

FIG. 14 is a scanning electron microscope view of a control example provided in example 5 of the present invention using microspheres prepared in small batches;

FIG. 15 is a scanning electron microscope view of a comparative example provided in example 5 of the present invention using microspheres prepared in large quantities.

Reference numerals illustrate:

100. preparing a feeding component by using microspheres;

110. a water phase feed pipe;

111. a feed end pipeline; 112. a discharge end pipeline; 113. an aqueous phase feed channel;

114. a connection port;

1141. a through hole; 1142. a threaded connection section; 1143. a pipeline connecting section;

115. a connection structure;

120. an oil phase feed pipe;

121. an outer wall threaded connection section; 122. a sealing member;

200. a homogenizer;

210. a homogenizer body; 220. a homogenizer feed inlet; 230. and a discharge hole of the homogenizer.

Detailed Description

For the purpose of making the objects, technical solutions and advantages of the present invention more apparent, embodiments of the present invention will be described in further detail below with reference to the accompanying drawings.

Example 1

The embodiment of the present example provides a microsphere preparation feed assembly 100. Referring to fig. 1, the microsphere preparation feed assembly 100 includes an aqueous phase feed pipe 110 and an oil phase feed pipe 120. The water phase feeding pipe 110 includes a feeding end pipe 111 and a discharging end pipe 112 connected to each other, and respective ends of the feeding end pipe 111 and the discharging end pipe 112 are connected to each other, and a water phase feeding passage 113 having the same inner diameter and penetrating the feeding end pipe 111 and the discharging end pipe 112 is formed inside. The feeding end pipeline 111 extends along a direction inclined away from the discharging end pipeline 112, and an included angle between the feeding end pipeline 111 and the axis of the discharging end pipeline 112 is an obtuse angle. And, air or bubbles in the aqueous phase at the junction of each other through the feed end pipe 111 and the discharge end pipe 112 can be discharged along the aqueous phase feed passage.

One end of the oil phase feeding pipe 120 extends into the water phase feeding channel 113, and the axis of the oil phase feeding pipe 120 is parallel to the axis of the discharging end pipeline 112. And, the outer wall portion of the end portion of the feed end pipeline 111 near the discharge end pipeline 112 side is provided with a connection port 114, the oil phase feed pipe 120 extends into the water phase feed channel 113 through the connection port 114, and the oil phase feed pipe 120 is detachably and fixedly connected with the connection port 114, and one end of the oil phase feed pipe 120 extending into the water phase feed channel 113 extends out of the other end of the discharge end pipeline 112 far away from the feed end pipeline 111.

Specifically, in this embodiment, referring to fig. 2 and 3, the oil phase feeding pipe 120 is detachably sleeved on the water phase feeding pipe 110, a part of the oil phase feeding pipe 120 is located in the water phase feeding pipe 110, and the inner diameter of the oil phase feeding pipe 120 is far smaller than that of the water phase feeding pipe 110.

It will be appreciated that the oil phase feed pipe 120 may be removably disposed on the water phase feed pipe 110 in various ways, and is not limited to connection through the connection port 114, for example, a recess is disposed on the feed end pipe 111 of the water phase feed pipe 110, and the oil phase feed pipe 120 is sleeved on the water phase feed pipe 110 through the recess, and may be removably replaced by a clip connection, a screw connection, or the like.

Further, the axial angle between the inlet pipe 111 and the outlet pipe 112 is greater than 90 ° and less than 180 °, for example, 91 °, 110 °, 120 °, 145 °, 160 °, 179 °, etc., in this embodiment, the angle is preferably in the range of 100 ° to 140 °, and more preferably 120 °.

Still further, the microsphere preparation feed assembly 100 disclosed herein includes an aqueous phase feed pipe 110 for separately feeding an aqueous phase and an oil phase feed pipe 120 for separately feeding an oil phase. The water phase inlet pipe 110 comprises feed end pipeline 111 and discharge end pipeline 112 to feed end pipeline 111 extends along the direction of keeping away from for the slope of discharge end pipeline 112, has such structure, when having air or bubble in the water phase inlet pipe, air or bubble will be discharged to the feed port along feed end pipeline 111, and because there is pressure differential between feed end and the discharge end, more be favorable to air or bubble to discharge, thereby furthest reduces air or bubble in the water phase inlet pipe, avoids appearing air or bubble unable to get rid of the condition that gets into in the homogenizer 200, further avoids appearing the condition such as hollow emulsion drop after the homogeneity. In another implementation manner, air or air bubbles can be discharged from the discharge port by increasing the flow rate of the water phase, so that the microsphere preparation feeding assembly 100 provided by the application can enable the microsphere to have smoother and more round appearance when feeding to prepare the microsphere, and no hollow microsphere or microsphere fragments appear. And the unique structure of the water phase feeding pipe 110 can realize automatic exhaust, so that the exhaust is more rapid and convenient.

Further, one end of the oil phase feeding pipe 120 extending into the water phase feeding channel 113 extends out of the other end of the discharge end pipeline 112 far away from the feed end pipeline 111, i.e. in the vertical direction, the discharge port of the oil phase feeding pipe 120 is located below the water phase feeding pipe 110, the oil phase feeding pipe 120 is set to have a small diameter, the small diameter is designed to prevent the water phase from flowing backward into the oil phase, if the water phase flows backward into the oil phase, water-in-oil emulsion is generated in the oil phase feeding pipe 120, and finally the water-in-oil emulsion and the water phase form water-in-oil-in-water multiple emulsion in the homogenizing process. The water-in-oil-in-water compound emulsion can form hollow spheres after solidification, and the hollow spheres are easy to break into fragments after subsequent procedures such as screening, freeze-drying and the like. Through the design of the oil phase feeding pipe 120, the water phase can be prevented from flowing backwards or flowing backwards into the oil phase feeding pipe 120, and hollow microspheres or microsphere fragments are prevented from being generated, so that the preparation of high-quality and high-specification microspheres is ensured.

More specifically, the axis of the oil phase feeding pipe 120 is parallel to the axis of the discharge end pipeline 112, and referring to fig. 3, the axis of the oil phase feeding pipe 120 coincides with the axis of the discharge end pipeline 112, so that the oil phase flowing out of the discharge end of the oil phase feeding pipe 120 can be rapidly dispersed and mixed with the water flowing out of the discharge end pipeline 112, the dispersion and the mixing are more uniform, and the prepared microsphere is also more uniform and has higher quality.

More specifically, referring to fig. 3 and fig. 4, the ends of the feeding end pipeline 111 and the discharging end pipeline 112 are respectively provided with a connection structure 115, and the connection structure 115 may be a connection flange, a threaded connection end, a clamp, or other structures, for example, when the connection structure is set to be a clamp, the clamp of the feeding end pipeline 111 and the water phase driving component are clamped when the microsphere preparation feeding assembly 100 is used, and the clamp of the discharging end pipeline 112 and the feeding port of the homogenizer 200 are clamped, so that those skilled in the art can design or select according to actual requirements, and the embodiment is not limited thereto specifically.

The embodiment of this example also provides a microsphere preparation feeding assembly 100, please refer to fig. 4 and 5, in which the feeding end pipe 111 and the discharging end pipe 112 are both cylindrical pipes. And the included angle between the axes of the feeding end pipeline 111 and the discharging end pipeline 112 is in the range of 100-140 degrees.

Specifically, the included angle between the axes of the feed end pipe 111 and the discharge end pipe 112 may be 100 °, 110 °, 120 °, 130 °, or other angles, and preferably, the included angle between the axes of the feed end pipe 111 and the discharge end pipe 112 is 120 °. When the axial included angle between the feeding end pipeline 111 and the discharging end pipeline 112 is within the range of 100-140 degrees, air or bubbles in the water phase feeding pipe 110 can be timely and rapidly discharged, and meanwhile, the effective working length of the feeding end pipeline 111 and the discharging end pipeline 112 can be reduced, so that the structure is more simplified, and materials and cost are saved.

Embodiments of the present invention also provide a microsphere preparation feed assembly 100, the inner diameter of the aqueous phase feed channel 113 being in the range of 10mm to 30 mm.

The oil phase feed pipe 120 includes a plurality of replaceable oil phase feed pipes 120, and the inner diameter of the plurality of replaceable oil phase feed pipes 120 is in the range of 0.5mm to 5 mm.

It may be preferable, further based on experimental data, that the inner diameter of the aqueous phase feed channel 113 is in the range of 10mm to 20mm, and further that the inner diameter of the aqueous phase feed channel 113 is 16mm.

Further according to experimental data, it may be preferable that the inner diameter of the oil phase feed pipe 120 is in the range of 0.5mm to 3mm, and further an optimal value is that the inner diameter of the oil phase feed pipe 120 is 1.6mm.

According to experiments of the applicant, in the microsphere preparation feed assembly 100 provided by the application, when the inner diameter of the water phase feed channel 113 is in the range of 10mm to 30mm, the flow rate of the water phase in the water phase feed channel 113 can be kept at a better value, in the flow rate range, the water phase entering the homogenizer can rapidly perform homogenization reaction with the oil phase, the quality of the finally obtained microspheres is higher, the inner diameter of the water phase feed channel 113 is in a better value in the range of 10mm to 20mm, and experimental data show that when the inner diameter of the water phase feed channel 113 is in the range of 14mm to 18mm, the flow rate of the water phase, the homogenization reaction speed, the uniformity of the microspheres and the quality and yield of the microspheres are all in optimal values, and similarly, when the inner diameter of the oil phase feed pipe 120 is in the range of 0.5mm to 3mm, the flow rate and the homogenization reaction speed of the oil phase can be ensured, and further, when the inner diameter of the oil phase feed pipe 120 is in the range of 1.4mm to 1.8m, the flow rate, the homogenization reaction speed, the uniformity of the microspheres and the quality and the yield of the oil phase can all be obtained.

The replaceable oil phase feed pipe 120 may be provided with 3, 4, 5 or more, and the inner diameters of the plurality of different replaceable oil phase feed pipes 120 may be different. In this way, the oil phase feeding pipe 120 is set to be a plurality of replaceable oil phase feeding pipes 120, and the inner diameters of the plurality of replaceable oil phase feeding pipes 120 are different, so that the replaceable oil phase feeding pipes 120 with different inner diameters can be selected according to the viscosity, feeding speed and other requirements of the oil phase to be used, the oil phase feeding pipe 120 is convenient to use and can meet larger application scenes, and the oil phase feeding pipe 120 is set to be a small-caliber inner diameter, so that the water phase can be prevented from flowing backwards into the oil phase, the formation of water-in-oil emulsion is avoided, and the formation of hollow emulsion drops during homogenization is further avoided.

For example, 3 replaceable oil phase feeding pipes 120 are provided, the inner diameters of which are respectively 1.0mm, 1.6mm and 2.5mm, when the viscosity and feeding speed of the oil phase are large, the replaceable oil phase feeding pipes 120 with the inner diameter of 2.5mm can be selected according to the requirement, when the viscosity and feeding speed of the oil phase are small, the replaceable oil phase feeding pipes 120 with the inner diameter of 1.0mm can be selected according to the requirement, and under normal conditions, the replaceable oil phase feeding pipes 120 with the inner diameter of 1.6mm are preferably selected.

The embodiment of the present embodiment further provides a microsphere preparation feeding assembly 100, referring to fig. 4, the connection port 114 protrudes from the outer wall portion of the feeding end pipeline 111, the connection port 114 and the corresponding outer wall portion of the feeding end pipeline 111 have a through hole 1141 through which the oil phase feeding pipe 120 passes, and the inner wall portion of the connection port 114 is provided with a connection portion.

Referring to fig. 6, an outer wall portion of the oil phase feeding pipe 120 is provided with a connected portion adapted to and detachably connected with the connecting portion, and a sealing portion is further provided below the connected portion and is in sealing connection with an inner wall portion of the through hole 1141.

Specifically, the connecting portion and the connected portion may be provided as common various detachable connecting members, such as: the connection portion and the connected portion are configured as mutually-adapted sliding grooves and sliding rails, or the connection portion and the connected portion are configured as mutually-adapted protrusions and grooves, or the connection portion and the connected portion are configured as mutually-adapted internal thread structures and external thread structures, or are connected through a chuck structure, and it should be understood by those skilled in the art that the structure satisfying the detachable connection between the outer wall portion of the oil phase feed pipe 120 and the inner wall portion of the connection port 114 can be designed according to actual requirements, which is not particularly limited in this embodiment. Through the design of the structure, the through hole 1141 of the oil phase feeding pipe 120 penetrating through the connecting port 114 is detachably connected with the connecting port 114, and the structure can conveniently replace oil phase pipes with different inner diameters, and the sealing part is in sealing connection with the inner wall part of the through hole 1141, so that the sealing property of the end part of the oil phase feeding pipe 120 connected with the water phase feeding pipe 110 is ensured.

Preferably, referring to fig. 4 and 6, the microsphere preparation feeding assembly 100 disclosed in the embodiment of the present invention includes a threaded connection section 1142 and a pipe connection section 1143, the threaded connection section 1142 is provided with an internal thread, the pipe connection section 1143 is provided with a smooth inner wall surface, and the pipe connection section 1143 is located on a side of the threaded connection section 1142 closer to the discharge end pipe 112.

The connected part comprises an outer wall threaded connection section 121 and a sealing member 122 positioned on one side of the outer wall threaded connection section 121, the outer wall threaded connection section 121 is detachably and adaptively connected with the threaded connection section 1142, the sealing member 122 is in interference fit with the inner wall surface of the pipeline connection section 1143, and meanwhile the sealing member 122 is in sliding fit with the pipeline connection section 1143. Also, in the axial direction of the oil phase feed pipe 120, the axial extension length of the outer wall screw connection section 121 is greater than the axial extension length of the screw connection section 1142.

Specifically, in this embodiment, the sealing member 122 may be any one of a common sealing plug, a sealing ring, a pressing ring, and a PEEK pressing plug, and the axial extension length of the outer wall threaded connection section 121 is greater than the axial extension length of the threaded connection section 1142, the extension length of the oil phase feeding pipe 120 (the extension length in the homogenizer 200) relative to the water phase feeding pipe 110 is adjusted by rotationally adjusting the threaded connection lengths of the outer wall threaded connection section 121 and the threaded connection section 1142, for example, the adjustable allowance is at least 10mm when the axial extension length of the outer wall threaded connection section 121 is greater than the axial extension length of the threaded connection section 1142 by more than 10mm, or may be set to other length values according to the requirement, and the axial extension length of the threaded connection section 1142 may be set to be greater than the axial extension length of the outer wall threaded connection section 121 according to the requirement.

By adopting the design of the structure, the connecting part and the connected part are arranged into the mutually matched internal thread and external thread structure, the replacement and the disassembly are more convenient, and the sealing member 122 is arranged to improve the sealing performance. And the axial extension length of the outer wall threaded connection section 121 on the oil phase feeding pipe 120 is larger than that of the threaded connection section 1142, and through the design of the structure, the height of the oil phase feeding pipe 120 can be adjusted according to the requirement.

The embodiment of the present embodiment further provides a microsphere preparation feeding assembly 100, where the inner wall surface of the corresponding end portion where the feeding end pipeline 111 and the discharging end pipeline 112 are connected is in a smooth curved surface shape (not shown in the figure). By adopting the structural design, when the inner wall surface of the corresponding end part of the connection between the feeding end pipeline 111 and the discharging end pipeline 112 is in a gentle curved surface shape, the water phase can avoid generating bubbles or air or reduce the generation of bubbles or air when flowing in the water phase feeding pipe 110, and the flowing is more stable, so that the quality of the formed microspheres is improved.

In summary, the microsphere preparation feeding assembly 100 disclosed in this embodiment includes an aqueous phase feeding tube 110 and an oil phase feeding tube 120, the aqueous phase feeding tube 110 includes a feeding end tube 111 and a discharging end tube 112 connected to each other, the feeding end tube 111 extends along a direction inclined away from the discharging end tube 112, and an included angle between the feeding end tube 111 and an axis of the discharging end tube 112 is an obtuse angle, when air or bubbles are in the aqueous phase feeding tube, the air or bubbles will be discharged to the feeding port or the discharging port along the feeding end tube 111, and because of a pressure difference between the feeding end and the discharging end, the air or bubbles are more easily discharged, thereby minimizing the air or bubbles in the aqueous phase feeding tube, avoiding the situation that the air or bubbles cannot be discharged into the homogenizer 200, and further avoiding the situation that hollow emulsion drops after homogenization. Therefore, the microsphere preparation feeding assembly 100 provided by the application can enable the microsphere to be smoother and more round when feeding to prepare the microsphere, and no hollow microsphere and microsphere fragments appear. The discharge gate of oil phase inlet pipe 120 is located the below of water phase inlet pipe 110, sets up oil phase inlet pipe 120 to the internal diameter of small-bore, and this small-bore design can avoid the water phase to flow backward or flow back into oil phase inlet pipe 120, avoids hollow microsphere or microsphere piece to produce, can also select the alternative oil phase inlet pipe 120 of different internal diameters according to the viscosity of used oil phase and demand such as feed rate, convenient to use just can satisfy bigger application scenario.

Example 2

Embodiments of the present example also provide a homogenizer 200, see fig. 7, the homogenizer 200 comprising the microsphere preparation feed assembly 100 of any of example 1, and further comprising:

the homogenizer body 210, the homogenizer body 210 includes homogenizer feed inlet 220 and homogenizer discharge gate 230, and homogenizer feed inlet 220 and the discharge end pipeline 112 detachably sealing connection of aqueous phase inlet pipe 110, and the homogenizer discharge gate 230 sets up in the one side of homogenizer body 210, has the homogeneity cavity in the homogenizer body 210, and homogenizer feed inlet 220 and homogenizer discharge gate 230 communicate with the homogeneity cavity respectively. Wherein the homogenizing chamber is in communication with the aqueous phase feed channel 113 in the discharge end conduit 112, the respective ends of the oil phase feed pipe 120 extend out of the aqueous phase feed channel 113, and the oil phase feed pipe 120 is in communication with the homogenizing chamber. The axial direction of the homogenizer discharge port 230 is perpendicular to the axial direction of the homogenizer feed port 220.

With this structural design, the water phase and the oil phase will enter the homogenizing cavity for homogenization through the homogenizer feed port 220, and because of the design of the oil phase feed pipe 120 and the water phase feed pipe 110 in the present application, no air or air bubbles will enter the homogenizing cavity, and no multiple emulsion droplets of water-in-oil, water-in-oil-in-water, etc. will be formed. Therefore, the microspheres with uniform size and smooth outer wall can be formed, hollow microspheres, microsphere fragments and the like can not be generated, and the quality of the prepared microspheres is improved.

It should be noted that, when the oil phase is conveyed through the inlet of the oil phase feeding pipe 120, the oil phase may be pumped through, but not limited to, an oil phase peristaltic pump, and when the water phase is conveyed through the inlet of the water phase feeding pipe 110, the water phase may be pumped through, but not limited to, an aqueous phase peristaltic pump, and the feeding ratio of the oil phase and the water phase may be controlled by adjusting the rotation speed of the oil phase peristaltic pump.

Example 3

The embodiment of the present embodiment further provides a method for preparing a microsphere, where the method for preparing a microsphere is applied to the homogenizer, and the method for preparing a microsphere includes:

the oil phase is prepared from polymer and dichloromethane, the mass ratio of the polymer to the dichloromethane is 1:X, and the oil phase with the concentration of 1/(1+X) percent is prepared after stirring and dissolving. The value of X is in the range of 4-19, and the corresponding oil phase concentration is between 5% and 20%, for example, when the mass ratio of the polymer to the dichloromethane is 1:9, the oil phase with 10% concentration is prepared after stirring and dissolving, or when the mass ratio of the polymer to the dichloromethane is 2:8, the oil phase with 20% concentration is prepared after stirring and dissolving, and regarding the preparation of the oil phase, the concentration of the oil phase can be prepared according to actual requirements by a person skilled in the art, and the embodiment is not limited in particular.

Preparing a water phase, wherein the water phase is prepared from a surfactant and pure water, the mass ratio of the surfactant to the pure water is 1:Y, and stirring and dissolving the mixture at the reaction temperature of 20-99 ℃ to obtain the water phase with the concentration of 1/(1+Y)%. The Y value is in the range of 19 to 199, the corresponding water phase concentration is between 0.5% and 5%, for example, the mass ratio of the surfactant to the pure water is 1:99, the water phase with 1% concentration is prepared by stirring and dissolving at the reaction temperature of 20 to 99 ℃, or the mass ratio of the surfactant to the pure water is 2:98, the water phase with 2% concentration is prepared by stirring and dissolving at the reaction temperature of 20 to 99 ℃, and regarding the preparation of the water phase, the concentration of the water phase can be prepared according to actual requirements by a person skilled in the art, and the embodiment is not particularly limited.

The oil phase after preparation is pumped into the homogenizer by the oil phase feeding pipe, the water phase is pumped into the homogenizer by the feeding end pipeline of the water phase feeding pipe, the liquid inlet mass ratio of the oil phase to the water phase is 1:Z, the Z value is in the range of 5-15, the liquid inlet mass ratio of the corresponding oil phase to the water phase is 1:5-1:15, for example, the liquid inlet mass ratio of the oil phase to the water phase is 1:9, 1:10, 1:13, and the like, and the embodiment is not limited in particular.

The oil phase and the water phase enter the homogenizer, and after 10-30 seconds from the beginning of homogenization, the emulsion is obtained by sampling from the discharge port of the homogenizer, for example, the homogenization time can be 10 seconds, 20 seconds, 30 seconds, and the like.

And (3) an emulsion curing step, namely pouring the emulsion into curing water, wherein the mass ratio of the emulsion to the curing water is 1:alpha, and stirring and curing the mixed solution of the emulsion and the curing water for 2-4 hours to obtain the preliminarily cured microsphere. In this step, the alpha value is in the range of 5-20, the mass ratio of the emulsion to the curing water can be 1:5, 1:6, 1:7, 1:8 or any ratio of 1:5-1:20, and the mixed solution of the emulsion and the curing water can be stirred and cured for 2 hours, 3 hours, 4 hours and the like.

In the microsphere preparation method provided by the embodiment of the invention, the polymer can be any one of polycaprolactone, polylactic acid and polylactic acid-glycolic acid copolymer, and the aqueous phase preparation liquid comprises polyvinyl alcohol.

In this example, the values of X, Y, Z and α are proportional-fold values in the experimental process, and are not specific actual values. The method for preparing the microspheres may also be to prepare the oil phase and the water phase according to other methods or steps, and further prepare the microspheres, which is not particularly limited in this embodiment.

Example 4

It should be noted that, example 4 is two sets of control experiments, one set uses a homogenizer with a feeding assembly for microsphere preparation disclosed in the application as equipment, the microsphere preparation method is adopted to prepare and obtain microspheres, and the other set uses a traditional feeding assembly and a homogenizer as equipment, and the microspheres are prepared by the microsphere preparation method to carry out control verification, wherein the oil phase is polycaprolactone, and the water phase is polyvinyl alcohol.

1. Preparation experiment using microsphere preparation feed assembly and homogenizer disclosed herein as equipment:

step 1, preparing an oil phase, weighing 90g of PCL (polycaprolactone) with the molecular weight of 3 ten thousand, adding the PCL (polycaprolactone) into 810g of DCM (dichloromethane), and stirring for dissolution to obtain a PCL/DCM oil phase with the concentration of 10%.

And 2, preparing a water phase, weighing 100g of PVA (polyvinyl alcohol), adding into 9900g of pure water, heating and stirring at 80 ℃ to dissolve, and obtaining the PVA water phase with the concentration of 1%.

Step 3, adopt the microsphere preparation feed assembly that this application disclosed in example 1 and the homogenizer that example 2 disclosed to be preparation equipment, oil phase inlet pipe internal diameter is preferably with 1.6mm, and aqueous phase inlet pipe internal diameter is preferably with 16mm, and good oil water phase pipeline of connection sets up oily water phase feed flow, and oily water phase proportion is 1:10.

and 4, pumping the oil phase and the water phase into a homogenizer, and sampling from a discharge port of the homogenizer after 20 seconds from the beginning of homogenization to obtain emulsion. Looking at the emulsion state under the microscope, referring to fig. 8, it can be observed that the emulsion droplets are smooth and round under the optical microscope, and no hollow emulsion droplets exist.

And 5, pouring the emulsion into curing water, wherein the mass ratio of the emulsion to the curing water is 1:6, and stirring and curing the mixed solution of the emulsion and the curing water for 3 hours to obtain the preliminarily cured microsphere.

And step 6, removing redundant water phase on the surface of the microsphere through cleaning liquid after the primary solidification is finished and the microsphere is obtained.

And 7, freeze-drying the microspheres collected after the step of cleaning the microspheres by using a freeze dryer. The state of the microspheres was then observed under a scanning electron microscope, see fig. 9, and it can be seen that the microspheres under the scanning electron microscope were smooth and round, and no hollow microspheres and no fragments of microspheres were present.

2. Preparation experiments using existing (homogenizer-self) microsphere preparation feed assemblies and homogenizer-equipment (existing microsphere preparation feed assemblies can be seen in fig. 10 and 11), it should be noted that the procedure and method of the two preparation experiments are the same, except that the microsphere preparation feed assemblies are different:

Step 3, preparing a feeding component by using microspheres carried by a homogenizer (see fig. 10 and 11 for details) and connecting an oil-water phase pipeline by using the homogenizer as preparation equipment, setting an oil-water phase feeding flow, wherein the oil-water phase proportion is 1:10.

and 4, pumping the oil phase and the water phase into a homogenizer, and sampling from a discharge port of the homogenizer after 20 seconds from the beginning of homogenization to obtain emulsion. When the emulsion state was observed under a microscope, referring to fig. 12, it was clearly observed that there were more hollow emulsion droplets under an optical microscope.

And 7, freeze-drying the microspheres collected after the step of cleaning the microspheres by using a freeze dryer. Then, the state of the microspheres is observed under a scanning electron microscope, and referring to fig. 13, it can be clearly seen that a large number of hollow microspheres and microsphere fragments exist in the microspheres under the scanning electron microscope, and the quality of the prepared microspheres is poor.

In summary, it can be seen that in the two control experiments, the materials of the oil-water phase prepared by the microspheres are identical, the methods are identical, and the difference is only that the feed components prepared by the microspheres are different, but the quality difference of the prepared microspheres is very large, and the microspheres prepared by using the feed components prepared by the microspheres are uniform and smooth, and have no hollow spheres or sphere fragments. The microspheres prepared by adopting the existing (self-contained) microsphere preparation feeding assembly have a large amount of hollow microspheres and microsphere fragments, which seriously affect the quality of the microspheres.

Example 5

In this embodiment, two sets of control experiments are performed, both sets of control experiments use the homogenizer with the microsphere preparation feeding assembly disclosed in this application as equipment, and the microsphere is prepared and obtained by using the microsphere preparation method, which is different only in that one set of control experiments is a small-batch flow test and the other set of control experiments is a large-batch flow test, and it is noted that in this embodiment, the oil phase selects polylactic acid, and the water phase selects polyvinyl alcohol.

1. Experiment for preparing microspheres with small batch flow:

step 1, preparing an oil phase, weighing 90g of PLA (polylactic acid) with the molecular weight of 10 ten thousand, adding the PLA (polylactic acid) into 510g of DCM (dichloromethane), and stirring for dissolution to obtain a PLA/DCM oil phase with the concentration of 15%.

Step 3, the microsphere preparation feeding assembly disclosed in example 1 of the present application and the homogenizer disclosed in example 2 are adopted as preparation equipment, the inner diameter of an oil phase feeding pipe is preferably 1.6mm, the inner diameter of an aqueous phase feeding pipe is preferably 16mm, an oil-water phase pipeline is connected, and an oil-water phase feeding flow is set, wherein the oil phase feeding flow is 25g/min, the aqueous phase feeding flow is 250g/min, and the oil-water phase proportion is 1:10.

And 4, pumping the oil phase and the water phase into a homogenizer, and sampling from a discharge port of the homogenizer after 20 seconds from the beginning of homogenization to obtain emulsion. And 5, pouring the emulsion into curing water, wherein the mass ratio of the emulsion to the curing water is 1:6, and stirring and curing the mixed solution of the emulsion and the curing water for 3 hours to obtain the preliminarily cured microsphere.

And 7, freeze-drying the microspheres collected after the step of cleaning the microspheres by using a freeze dryer. The state of the microspheres was then observed under a scanning electron microscope, see fig. 14, and it can be seen that the microspheres under the scanning electron microscope were smooth and round, and no hollow microspheres and no fragments of microspheres were present.

2. Experiment for preparing microspheres at high flow rate:

Step 3, the microsphere preparation feeding assembly disclosed in example 1 of the present application and the homogenizer disclosed in example 2 are adopted as preparation equipment, the inner diameter of an oil phase feeding pipe is preferably 1.6mm, the inner diameter of an aqueous phase feeding pipe is preferably 16mm, an oil-water phase pipeline is connected, and an oil-water phase feeding flow is set, wherein the oil phase feeding flow is 110g/min, the aqueous phase feeding flow is 1100g/min, and the oil-water phase proportion is 1:10.

And 7, freeze-drying the microspheres collected after the step of cleaning the microspheres by using a freeze dryer. Then, the state of the microspheres was observed under a scanning electron microscope, and referring to fig. 15, it can be seen that the microspheres under the scanning electron microscope were smooth and round, and no hollow microspheres and microsphere fragments were present.

Referring to the two groups of control experiments in this embodiment specifically, it can be known that, in the two different control experiments of small batch (small flow)/large batch (large flow), the obtained microspheres are smooth and round and have no hollow microspheres and microsphere fragments, so that linear amplification can be realized, and the feeding component has higher stability and wider applicability when preparing the microspheres, and can meet various preparation requirements when in normal use.

In conclusion, according to the detection contrast of multiple experiments, the size of the microsphere prepared by the microsphere preparation feeding assembly, the homogenizer and the microsphere preparation method disclosed by the application is uniform, the outer wall of the microsphere is smooth, the quality of the microsphere is high, and impurities such as hollow microspheres and microsphere fragments are not generated.

It is intended that other advantages and effects of the present invention, in addition to those described in the specific embodiments, be readily apparent to those skilled in the art from the present disclosure. While the description of the invention will be described in connection with the preferred embodiments, it is not intended to limit the inventive features to the implementation. Rather, the purpose of the invention described in connection with the embodiments is to cover other alternatives or modifications, which may be extended by the claims based on the invention. The foregoing description contains many specifics, other embodiments, and examples of specific details for the purpose of providing a thorough understanding of the invention. Furthermore, some specific details are omitted from the description in order to avoid obscuring the invention. It should be noted that, without conflict, the embodiments of the present invention and features of the embodiments may be combined with each other.

It should be noted that in this specification, like reference numerals and letters denote like items in the following figures, and thus once an item is defined in one figure, no further definition or explanation thereof is necessary in the following figures.

In the description of the present embodiment, it should be noted that the azimuth or positional relationship indicated by the terms "upper", "lower", "inner", "bottom", etc. are based on the azimuth or positional relationship shown in the drawings, or the azimuth or positional relationship in which the inventive product is conventionally put in use, are merely for convenience of describing the present invention and simplifying the description, and are not indicative or implying that the apparatus or element to be referred to must have a specific azimuth, be configured and operated in a specific azimuth, and therefore should not be construed as limiting the present invention.

The terms "first," "second," and the like are used merely to distinguish between descriptions and are not to be construed as indicating or implying relative importance.

In the description of the present embodiment, it should also be noted that, unless explicitly specified and limited otherwise, the terms "disposed," "connected," and "connected" are to be construed broadly, and may be, for example, fixedly connected, detachably connected, or integrally connected; can be mechanically or electrically connected; can be directly connected or indirectly connected through an intermediate medium, and can be communication between two elements. The specific meaning of the above terms in the present embodiment can be understood in a specific case by those of ordinary skill in the art.

While the invention has been shown and described with reference to certain preferred embodiments thereof, it will be understood by those skilled in the art that the foregoing is a further detailed description of the invention with reference to specific embodiments, and it is not intended to limit the practice of the invention to those descriptions. Various changes in form and detail may be made therein by those skilled in the art, including a few simple inferences or alternatives, without departing from the spirit and scope of the present invention.

Claims

1. The microsphere preparation feeding assembly is characterized by comprising a water phase feeding pipe and an oil phase feeding pipe; wherein the method comprises the steps of

The water phase feeding pipe comprises a feeding end pipeline and a discharging end pipeline which are connected with each other, wherein the corresponding ends of the feeding end pipeline and the discharging end pipeline are connected with each other, and a water phase feeding channel with the same inner diameter and penetrating through the feeding end pipeline and the discharging end pipeline is formed inside the water phase feeding pipe; the feeding end pipeline extends along a direction which is inclined and far away from the discharging end pipeline, and an included angle between the feeding end pipeline and the axis of the discharging end pipeline is an obtuse angle; and air or bubbles in the water phase at the mutually connected parts of the feeding end pipeline and the discharging end pipeline can be discharged along the water phase feeding channel;

One end of the oil phase feeding pipe extends into the water phase feeding channel, and the oil phase feeding pipe is parallel to the axis of the discharge end pipeline; and is also provided with

The oil phase feeding pipe is characterized in that a connecting port is arranged on the outer wall part of the feeding end pipe, which is close to one side end part of the discharging end pipe, the oil phase feeding pipe extends into the water phase feeding channel through the connecting port, the oil phase feeding pipe is detachably and fixedly connected with the connecting port, and one end of the oil phase feeding pipe extending into the water phase feeding channel extends out of the other end of the discharging end pipe, which is far away from the feeding end pipe.

2. The microsphere preparation feed assembly of claim 1, wherein the feed end conduit and the discharge end conduit are both configured as cylindrical conduits; and is also provided with

The included angle between the axes of the feeding end pipeline and the discharging end pipeline is 91-179 degrees.

3. The microsphere preparation feed assembly of claim 1, wherein the inner diameter of the aqueous phase feed channel is in the range of 10mm to 30 mm;

the oil phase feeding pipe comprises a plurality of replaceable oil phase feeding pipes, and the inner diameters of the plurality of replaceable oil phase feeding pipes are in the range of 0.5-5 mm.

4. A microsphere preparation feed assembly according to any one of claims 1 to 3, wherein the connection port protrudes from an outer wall portion of the feed end pipeline, the connection port and the corresponding outer wall portion of the feed end pipeline are provided with through holes for the oil phase feed pipe to pass through, and an inner wall portion of the connection port is provided with a connection portion;

The oil phase inlet pipe outer wall portion be provided with connecting portion adaptation, and can dismantle the connection by connecting portion to by connecting portion's below still is provided with sealing portion, sealing portion with the inner wall portion sealing connection of through-hole.

5. The microsphere preparation feed assembly of claim 4, wherein the connection comprises a threaded connection section and a pipeline connection section, the threaded connection section is provided with internal threads, the pipeline connection section is provided with a smooth inner wall surface, and the pipeline connection section is positioned on one side of the threaded connection section, which is closer to the discharge end pipeline; wherein the method comprises the steps of

The connected part comprises an outer wall threaded connection section and a sealing member positioned at one side of the outer wall threaded connection section, the outer wall threaded connection section is detachably and adaptively connected with the threaded connection section, and the sealing member is in interference fit with the inner wall surface of the pipeline connection section; and is also provided with

And in the axial direction of the oil phase feeding pipe, the axial extension length of the outer wall threaded connection section is larger than that of the threaded connection section.

6. The microsphere preparation feed assembly of claim 4, wherein the inner wall surfaces of the corresponding ends of the feed end pipeline and the discharge end pipeline are smooth curved surfaces.

7. A homogenizer comprising the microsphere preparation feed assembly of any of claims 1 to 6, and further comprising

The homogenizer body comprises a homogenizer feed inlet and a homogenizer discharge outlet, the homogenizer feed inlet is detachably and hermetically connected with a discharge end pipeline of the water phase feed pipe, the homogenizer discharge outlet is arranged on one side of the homogenizer body, a homogenizing cavity is arranged in the homogenizer body, and the homogenizer feed inlet and the homogenizer discharge outlet are respectively communicated with the homogenizing cavity; wherein the method comprises the steps of

The homogenizing cavity is communicated with the water phase feeding channel in the discharge end pipeline, the corresponding end part of the oil phase feeding pipe extends out of the water phase feeding channel, and the oil phase feeding pipe is communicated with the homogenizing cavity; and is also provided with

The axial direction of the discharge port of the homogenizer is perpendicular to the axial direction of the feed port of the homogenizer.

8. A method for preparing microspheres, wherein the method for preparing microspheres is used for the homogenizer of claim 7, and the method for preparing microspheres comprises the steps of:

preparing an oil phase, wherein the oil phase is prepared from a high polymer raw material and methylene dichloride, the mass ratio of the high polymer raw material to the methylene dichloride is 1:X, and stirring and dissolving the mixture to prepare an oil phase with the concentration of 1/(1+X)%;

Preparing a water phase, wherein the water phase is prepared from a surfactant and pure water, the mass ratio of the surfactant to the pure water is 1:Y, and stirring and dissolving the mixture at a reaction temperature of 20-99 ℃ to obtain a water phase with 1/(1+Y)% concentration;

pumping the oil phase after preparation into the homogenizer by the oil phase feeding pipe, pumping the water phase into the homogenizer by a feeding end pipeline of the water phase feeding pipe, and enabling the liquid inlet mass ratio of the oil phase to the water phase to be 1:Z;

the oil phase and the water phase enter the homogenizer, and after 10-30 seconds from the beginning of homogenization, the sample is taken from the discharge port of the homogenizer to obtain emulsion; wherein the method comprises the steps of

The X value is in the range of 4 to 19, the Y value is in the range of 19 to 199, and the Z value is in the range of 5 to 15.

9. The method of preparing microspheres according to claim 8, further comprising:

pouring the emulsion into the curing water, wherein the mass ratio of the emulsion to the curing water is 1:alpha, and stirring and curing the mixed solution of the emulsion and the curing water for 2-4 hours to obtain the preliminarily cured microsphere;

and cleaning the microspheres, namely removing redundant water phase on the surfaces of the microspheres through cleaning liquid after the primary solidification is finished and the microspheres are obtained.

Lyophilizing the microspheres, namely lyophilizing the microspheres obtained by collecting the microspheres after the step of cleaning the microspheres by using a lyophilizer; wherein the method comprises the steps of

The alpha value is in the range of 5 to 20.

10. The method according to claim 8, wherein the polymer material is one of polycaprolactone, polylactic acid, and a polylactic acid-glycolic acid copolymer, and the aqueous preparation solution comprises polyvinyl alcohol.