TWI631962B - Microspheres granulation device based on spherical shape control - Google Patents

Abstract

The present invention provides a microsphere granulation device based on spherical shape control, comprising: a feeding device connected to a nozzle, the nozzle having an output end; the feeding device is for conveying liquid heat sensitive material to The nozzle forms a liquid microsphere and is output through the output end; a cooling unit that cools the interface of the microsphere to form a rigid coating layer at a temperature lower than a freezing point of the heat sensitive material If the microspheres are collected, the microspheres are prevented from being deformed by the impulse to maintain the sphericity of the microspheres, thereby improving the yield of the microspheres and preventing the deformation when used for embolization. The tissue damage caused by the microspheres.

Description

Microsphere granulator based on spherical shape control

The invention provides a microsphere granulating device based on spherical shape control, in particular, a phenomenon in which a microsphere can be prevented from being subjected to a force during a process of preparing a microsphere.

According to the report, liver cancer causes more than one million deaths every year in the world, which is one of the common lethal cancers. According to statistics from the Department of Health of the Executive Yuan, liver cancer accounts for males in the cause of death in Taiwan in 1992. The first place (22.78%) and the second place (14.94%).

At present, the treatment methods of liver cancer include: surgical resection, alcohol injection, radiofrequency ablation, liver transplantation and other eradication treatments. For those who cannot receive eradication therapy, local non-eradicity of local tumor arterial embolization or radiation irradiation can be selected. Treatment, in the past, systemic chemotherapy is the only active treatment option, but liver cancer cells often have endogenous, multi-drug resistance, and cirrhosis, so systemic chemotherapy often has poor results and significant side effects, regardless of Chemotherapy with a single drug or multiple drugs, the effect is only about 10% to 20%, while the normal liver 70% to 75% of the blood is supplied by the portal vein of the intestine and spleen, 25% to 30% It is provided by the hepatic artery. The liver cancer cell nutrients are 90% to 95% derived from the hepatic artery. Therefore, transcatheter hepatic artery embolization can be used to block arterial blood flow, so that liver cancer cells are necrotic due to lack of nutrient supply, so as to achieve liver cancer. The healing effect.

Therefore, embolization products commonly used to treat liver cancer such as: gelatin (Delfoam), drug-free embolization microspheres (Embosphere), drug-released microspheres (Drug-eluting beads-DC beads), and radioactive isotope Yttrium-90 embolization microspheres Microspheres made of functional materials; in terms of gelatin, the price is relatively cheap, but it is made by most medical institutions, and there is no process control, so there are great problems in particle size, disinfection ability and quality. The quality of the medical products is affected; the embolic microspheres without drug release are expensive, about 0.5ml is the price of thousands of dollars; if the drug releases the embolic microspheres or carries the radioactive isotope Yttrium-90 embolization microspheres, the price is even 0.5ml or even It can take tens of thousands to hundreds of thousands.

The main reason for the high price of the above-mentioned embedding microspheres is that the process and particle size control are not easy, and the size of the medical embedding microspheres is different due to the different embedding organs, and the required size is also very different, so it requires a lot of precision instruments and The control equipment can reach the size of the particle size; in addition, the microspheres are easy to produce particle surface change due to the different collection system conditions. For example, the conventional microspheres are output by the nozzle and collected by the collection system. In the process of collecting the aggregate, the microsphere will be deformed by the impact of the nozzle output and the collection system. As shown in Fig. 1, since the microsphere 10 is output, it is a gel with a viscosity. When the collection system is a solution, the microspheres 10 are affected by the surface tension and the interface resistance when passing through the interface 30 of the solution 20, and the microspheres 10 are deformed by extrusion stretching, so that the sphericity of the microspheres 10 is lowered, and In some cases, the tip portion 101 will be produced, which will cause damage to the cell tissue during embolization treatment; furthermore, if the microsphere 10 is deformed, it is a mixture of composite materials, when it is dried and stored. When rehydration is used, it will Caused by uneven expansion of its extent, the situation caused the type of change become more significant, its impact will cause the effect of embolization, thereby affecting the quality of care and the rights and interests of patients.

In view of this, our inventors have devote themselves to further research on the preparation of microspheres, and have initiated research and development and improvement, with a preferred invention to solve the above problems, and have been experimentally and modified to have the present invention.

That is, the object of the present invention is to solve the above problems. To achieve the above object, the inventors provide a microsphere granulation device based on spherical shape control, comprising: a feeding device, which is provided with a nozzle in communication The nozzle has an output end, the output end sequentially defining a first section and a second section; the feeding device is configured to transport a liquid heat sensitive material to the nozzle to form a liquid microsphere, and An output terminal; and a cooling unit disposed in the second section and corresponding to the output end, the cooling unit is applied to the second section by cooling below a freezing point of the heat sensitive material The interface of the microspheres is formed into a rigid coating.

According to the above-mentioned microsphere granulation device based on spherical shape control, wherein the periphery of the nozzle is further provided with at least a first-class channel, and the flow channel outputs a jet flow to output the heat-sensitive material to the output end. Atomization is performed to form the microspheres.

According to the above-mentioned microsphere granulation device based on spherical shape control, wherein the periphery of the nozzle is further provided with at least a first channel, the flow channel outputs a first medium for outputting the microsphere At the output end, the first medium is coated on the microsphere, and the first medium is a liquid material having a freezing point lower than the heat sensitive material, and the cooling unit is lower in temperature than the first Cooling of the freezing point of the medium acts on the second section such that the first medium forms a rigid coating on the interface of the microspheres.

The microsphere granulation device based on the spherical shape control according to the above, further comprising at least one side flow channel disposed in the first segment, and corresponding to the output end, the side flow channel output is a medium, the second medium is coated on the surface of the microsphere, and the second medium is a liquid or gaseous material having a freezing point lower than the heat sensitive material, and the cooling unit is at a temperature lower than the Cooling of the freezing point of the second medium acts on the second section such that the second medium forms a rigid coating on the interface of the microspheres.

According to the microsphere granulating device based on the spherical shape control described above, the side channel is inclined at an inclination angle toward the moving direction of the microsphere.

The microsphere granulation device based on the spherical shape control according to the above, further includes a third segment correspondingly defined at an end of the second segment, and the third segment is provided with a corresponding one of the outputs The collecting device, and the collecting device comprises a container containing the collecting liquid.

The microsphere granulation device based on the spherical shape control according to the above, further comprises a cabin, the cabin is an insulated space, and the feeding device and the nozzle are disposed at the top of the tank, the cooling unit It is disposed at a side end of the cabin, and the collecting device is disposed at a bottom end of the cabin.

The microsphere granulation device based on the spherical shape control according to the above, further includes a third segment correspondingly defined at an end of the second segment, and the third segment is provided with a corresponding one of the outputs a collecting device comprising: a container containing a collecting liquid, wherein the collecting liquid is a reaction liquid capable of generating a chemical reaction with the heat sensitive material, and the chemical reaction means the heat sensitive material The surface forms a coating film.

The microsphere granulator according to the above-described spherical shape control according to the above, wherein the heat sensitive material contains alginate, and the collected liquid contains calcium chloride (CaCl2).

The microsphere granulating device based on the spherical shape control according to the above, wherein the container is further provided with a heating device for heating the collected liquid to a temperature slightly higher than a freezing point of the heat sensitive material.

According to the microsphere granulating device based on the spherical shape control described above, the container is further provided with a driving unit for causing the collected liquid to generate a flow.

According to the microsphere granulating device based on the spherical shape control described above, the cooling unit outputs a vortex airflow containing liquid nitrogen.

The microsphere granulation device based on the spherical shape control according to the above, wherein the feeding device is an injection device, and at least one thermostat corresponding to the heat sensitive material is disposed outside the feeding device.

It is obvious from the above description and setting that the present invention has the following several advantages and effects, which are detailed as follows:

1. The invention provides a rigid coating layer by solidifying the interface of the microspheres or the first medium or the second medium on the surface of the microspheres by the arrangement of the cooling unit, thereby collecting the microspheres. Preventing the microsphere from being deformed by the force, and when it falls into the collecting liquid, it is not affected by the surface tension of the collecting liquid, and the influence of the interface resistance between the collecting liquid and the coating layer causes the microsphere to be deformed by extrusion stretching, so that it can be maintained The sphericity of the microspheres can improve the yield of the microspheres, and when used for embolization treatment, can prevent the tissue damage caused by the modified microspheres, thereby improving the quality of embolization treatment.

2. The invention can form a coating film by chemical reaction between the collecting liquid and the microsphere formed by the heat sensitive material, and can also form a coating layer by cooling the first medium or the second medium, whereby the heat sensitive material is When the drug is used, it can achieve the effect of fixed-point release or delayed release of the drug.

[study]

10‧‧‧microspheres

101‧‧‧ tip

20‧‧‧solution

30‧‧‧ interface

〔this invention〕

1‧‧‧Feeding device

11‧‧‧ thermostat

2‧‧‧ nozzle

21‧‧‧ Output

3‧‧‧Thermal materials

3’‧‧‧microspheres

3"‧‧‧ Cover film

31‧‧‧First medium

32‧‧‧Second medium

4‧‧‧ flow path

41‧‧‧Air intake

42‧‧‧ Side runner

5‧‧‧Cooling unit

6‧‧‧ Collector

61‧‧‧ collecting liquid

62‧‧‧ Container

63‧‧‧ heating device

64‧‧‧Drive unit

7‧‧‧ cabin

80, 81, 82‧‧ ‧ coating

90, 91, 92, 93‧‧‧ particles

A‧‧‧ first section

B‧‧‧Second section

C‧‧‧third section

Fig. 1 is a schematic view showing a conventional microsphere that enters a liquid interface to produce a tip end portion.

Fig. 2 is a schematic view showing the structure of the first embodiment of the present invention.

Fig. 3 is a schematic diagram showing the temperature versus viscosity of the heat sensitive material of the present invention in a temperature sensitive medical functional material having a different concentration.

Fig. 4 is a schematic view showing a coating layer and microspheres of the first embodiment of the present invention.

Fig. 5 is a schematic view showing the movement path of the microspheres in the second section of the first embodiment of the present invention.

Fig. 6 is a schematic view showing the microsphere of the first embodiment of the present invention falling into a collecting liquid.

Fig. 7 is a schematic view showing the particles formed in the first embodiment of the present invention.

Figure 8 is a schematic view showing the structure of a second embodiment of the present invention.

Figure 9 is a schematic view of the particles formed in the second embodiment of the present invention.

Figure 10 is a schematic view showing the structure of a third embodiment of the present invention.

Figure 11 is a schematic view showing the particles formed in the third embodiment of the present invention.

Figure 12 is a schematic view showing the structure of a fourth embodiment of the present invention.

Figure 13 is a schematic view showing the particles formed in the fourth embodiment of the present invention.

Annex 1 is an experimental diagram of atomizing a heat sensitive material into microspheres in the first embodiment of the present invention.

Attachment 2 is an experimental result diagram of the microparticles formed in the first embodiment of the present invention, having a magnification of 30 times and a particle size ranging from 37 um to 75 um.

Attachment 3 is an experimental result diagram of the microparticles formed in the first embodiment of the present invention, having a magnification of 20 times and a particle size ranging from 75 um to 106 um.

Attachment 4 is an experimental result diagram of particles formed by the first embodiment of the present invention, having a magnification of 20 times and a particle size ranging from 106 um to 150 um.

The accessory 5 is an experimental result chart of the microparticles formed in the first embodiment of the present invention, the magnification is 20 times, and the particle diameter ranges from 150 um to 250 um.

The invention will be described in detail below with reference to the drawings.

Please refer to FIG. 2, which is a first embodiment of the present invention. The present invention is a microsphere granulation device based on spherical shape control, comprising: a feeding device 1 connected to a nozzle 2 The nozzle 2 has an output end 21, which defines a first section A and a second section B in sequence; the feeding device 1 is for conveying a liquid heat sensitive material 3 to the nozzle 2 forming a liquid microsphere 3' and outputting through the output end 21; in an embodiment, for the heat sensitive material 3, because of its heat sensitivity, that is, the viscosity of the heat sensitive material 3 will vary due to temperature. Change, as shown in Fig. 3, in one embodiment, the heat sensitive material 3 is 5.66% temperature sensitive medical functional material, the main component is alginate (Na-alginate, sodium alginate) and other composites The material has a viscosity of 1800 cP at room temperature, which is favorable for the nozzle 2 to output it as a microsphere 3' type, or to facilitate the atomization of the microspheres 3' having a small diameter of 10', so that the viscosity is required to be lowered. Therefore, in the present embodiment, the heat sensitive material 3 is heated to 90 ° C, and at this time, the viscosity is 214.5 cP, which is beneficial to In a preferred embodiment, in order to maintain the viscosity and feed rate of the heat sensitive material 3, to control the particle size of the microspheres 3', the feeding device 1 is an injection device, thereby controlling the feeding. The flow rate is about 3 ml/min to 5 ml/min, and the outside of the feeding device 1 is provided with at least one constant temperature corresponding to the heat sensitive material 3 The apparatus 11 is configured to adjust the temperature and viscosity of the constant heat-sensitive material 3 during transportation. In the present embodiment, the thermostat device 11 can be set to a constant temperature of 90 ° C, which is merely illustrative and not limited thereto; In the embodiment, the nozzle 2 outputs the heat sensitive material 3, and in another embodiment, the nozzle 2 has an inner diameter of 300 um, an outer diameter of 1000 um, the feed flow rate by the feeding device 1, and the heat sensitive material 3 The surface tension is formed by the output end 21 of the nozzle 2 to form the microsphere 3' output. In a preferred embodiment, in order to further reduce the particle size of the microsphere 3', at least the first edge of the nozzle 2 can be provided. In the embodiment 4, the flow passage 4 outputs a jet flow, so the flow passage 4 can be connected to an intake device 41, and the intake pressure can be 0.1 bar to 0.5 bar. In this embodiment, the intake pressure system is It is set to 0.2 bar, and its experimental diagram is as shown in Annex 1. When the heat-sensitive material 3 is output to the output end 21, it can be atomized by the jet to form the microsphere 3', and the microsphere is controlled. The particle size of 3' is between 100um and 300um.

a cooling unit 5 is disposed in the second section B and corresponds to the output end 21, and the cooling unit 5 acts on the second section B with cooling lower than a freezing point of the heat sensitive material 3 In a preferred embodiment, the cooling unit 5 outputs a vortex flow containing liquid nitrogen; and in an embodiment, in order to facilitate the aggregate, a third section C is further included, which is defined At the end of the second section B, the third section C is provided with a collecting device 6 corresponding to the output end 21. In an embodiment, the collecting device 6 comprises a container containing the collecting liquid 61. The container 62 is only exemplified and is not limited thereto. In another embodiment, the container 62 may not be filled with the collecting liquid 61; in order to facilitate the stability of the overall process and the control of temperature, In a preferred embodiment, the system further includes a cabin 7 in which a heat insulating space is provided, and the feeding device 1 and the nozzle 2 are disposed at the top end of the cabin 7, and the cooling unit 5 is It is disposed at the side end of the tank 7, and the collecting device 6 is disposed at the bottom end of the tank 7.

Therefore, in the present embodiment, after the atomized microspheres 3' are delivered, the vortex flow containing the liquid nitrogen is outputted by the cooling unit 5, so that the temperature in the second section B is lowered, so that the second section B is The temperature is lower than the freezing point of the heat sensitive material 3, whereby the interface of the microsphere 3' is condensed into a solid coating layer 80, as shown in Fig. 4, and the vortex flow will cause the microsphere 3' to be in the second region. The movement path in the segment B is spiral, as shown in Fig. 5, so that the cooling efficiency can be further improved, and it is known that the coating layer 80 is solid, so it will have rigidity, so as shown in Fig. 6. It is shown that when the collecting device 6 collects the microspheres 3', the microspheres 3' are not easily impacted by the impact of the nozzles; and in order to prevent the temperature of the cooling unit 5 from interfering with the temperature of the nozzles 2, the height of the first section A can be utilized. The distance is reduced to the extent of interference.

In addition, in the embodiment, the collecting liquid 61 of the collecting device 6 is used to collect the microspheres 3'. In a preferred embodiment, the collecting liquid 61 is compatible. The heat sensitive material 3 generates a chemical reaction reaction solution for forming a coating film 3" on the surface of the heat sensitive material 3, as shown in Fig. 7, in a specific embodiment, The heat sensitive material 3 contains alginate, and the collecting liquid 61 contains calcium chloride (CaCl 2 ), so that when the microsphere 3 ′ falls into the collecting liquid 61 , a chemical reaction of the following chemical formula 1 is produced: [Chemical Formula 1] 】 2Na-alginate+CaCl ₂ → Ca-alginate+2NaCl

Wherein, Ca will adhere to the surface of the microsphere 3' to form the coating film 3", and NaCl will dissipate the gas; thereby, when the microsphere 3' is used for medical treatment, the coating film 3" is reachable The effect of a fixed point release or delayed release.

In addition, in terms of the container 62 and the collecting liquid 61, in order to achieve the reaction temperature of the heat sensitive material 3 and the collecting liquid 61, the solid heat sensitive material 3 condensed into the coating layer 80 needs to be softened, so that it is preferably implemented. In the example, the container 62 is further provided with a heating device 63 for heating the collecting liquid 61 to a temperature slightly higher than the freezing point of the heat sensitive material 3. In the present embodiment, the collecting liquid is used. 61 heated to 80 ° C, The coating layer 80 is softened and reacted with the collecting liquid 61 to form the coating film 3" to obtain the fine particles 90 coated with the microspheres 3' by the coating film 3'.

In a preferred embodiment, the container 62 is further provided with a driving unit 64, because the microspheres 3' will continue to fall into the collecting liquid 61, in order to prevent the dissimilar microspheres 3' from sticking to each other during the softening process. The collecting liquid 61 is caused to flow to avoid the adhesion between the microspheres 3' by the flow of the collecting liquid 61, or to separate the bonded microspheres 3', thereby improving the overall process yield of the present invention, and as an attachment. 2 to 5, it can be known that by adjusting the material, temperature, viscosity, feed flow rate, inlet pressure and pore diameter of the heat sensitive material 3, particles having a particle diameter of about 30 um to 300 um can be obtained. 90.

Continuing to refer to FIG. 8, which is a second embodiment of the present invention, which differs from the first embodiment in that the cladding layer 80 of the microsphere 3' of the first embodiment is cooled by the cooling unit 5. The interface of the microspheres 3' is formed by coagulation of the heat sensitive material 3 on the surface, and the coating film 3" for fixed-point release or delayed release is obtained by reacting the heat-sensitive material 3 with the collecting liquid 61. In the second embodiment, the first medium 31 is outputted by not outputting the jet flow to the flow path 4, whereby the output end 21 is outputted by each of the micro balls 3'. The first medium 31 is attached to the microspheres 3', and is affected by the surface tension of the first medium 31 and the microspheres 3', so that the whole body will still form a spherical shape; and the first medium 31 has a low freezing point. The liquid material of the heat sensitive material 3, and the cooling unit 5 acts on the second section B with a cooling temperature lower than the freezing point of the first medium 31, as shown in FIG. The first medium 31 forms a rigid coating layer 81 on the interface of the microspheres 3', thereby forming particles 9 coated with the microspheres 3' by the coating layer 81. 1; because the thickness of the first medium 31 is affected by the surface tension of the heat sensitive material 3 and the first medium 31, a thicker coating layer 81 will be formed; and when the cladding layer 81 is formed, It can be collected by the collecting device 6, and as described above, by the rigidity of the coating layer 81, deformation can be avoided by the impact; further, in the second embodiment, the coating is formed by the first medium 31. Layer 81 can select its material according to the needs, so when When the microsphere 3' is a drug, the effect of the fixed point release or the delayed release can be directly achieved by the first medium 31, so that the collecting device 6 can eliminate the use of the collecting liquid 61 or still use the collecting liquid 61, but need not be Corresponding to the liquid reacting with the heat sensitive material 3, or the collecting liquid 61 may also be a reaction liquid reacting with the first medium 31, which may be selected according to the needs of use; the remaining embodiments of the embodiment are the same as the first embodiment. The examples are similar, so they are not described here.

Continuing to refer to FIG. 10, which is a third embodiment of the present invention, which differs from the second embodiment in that a micro-sphere 3' having a smaller particle size is prepared, and a thin coating layer is provided. And the microsphere 3' is not reacted with the collecting liquid 61, so that the flow path 4 of the third embodiment can still be output as described in the first embodiment to atomize the heat sensitive material 3, and further, The third embodiment further includes at least one side flow channel 42 disposed in the first segment A, and corresponding to the output end 21, the side flow channel 42 outputs the second medium 32 to pass the microsphere 3' When the output area of the side flow channel 42 is applied, the second medium 32 is coated on the surface of the microsphere 3', and in order to increase the output range of the second medium 32, in an embodiment, The side flow channel 42 is inclined at an inclination angle θ toward the moving direction of the microsphere 3' to increase the coating yield; further, the second medium 32 has a freezing point lower than the heat sensitive material 3 a liquid or gaseous material, and the cooling unit 5 acts on the second section B with a cooling temperature lower than a freezing point of the second medium 32, whereby As shown, the second medium 32 forms a thin and rigid coating layer 82 on the interface of the microspheres 3' to coat the particles 92 of the microspheres 3'; and it is known that if a plurality of layers are to be formed The particles of the coating layer can be formed by the plurality of side channels 42 of the differential medium outputted by the second section B, and the plurality of particles are formed as described above; the remaining embodiments of the embodiment are similar to the second embodiment. Therefore, I will not repeat them here.

Referring to FIG. 12 again, it is a fourth embodiment of the present invention, which differs from the third embodiment in that the flow channel 4 of the fourth embodiment outputs the first medium 31 as described in the second embodiment. Thereby, when the first medium 31 covers the microspheres 3' and passes through the output range of the side flow channels 42, the second medium 32 will be recoated. Coating on the surface of the first medium 31, after the second section B is cooled by the cooling unit 5, the second medium 32 is formed into a rigid coating on the interface of the microspheres 3'. The layer 82, as shown in FIG. 13 , can be formed into a plurality of layers of particles 93 as required; the remaining embodiments of the embodiment are similar to those of the third embodiment, and thus are not described herein.

In summary, the technical means disclosed by the present invention can effectively solve the problems of the prior knowledge, achieve the intended purpose and efficacy, and are not found in the publication before publication, have not been publicly used, and have long-term progress, The invention referred to in the Patent Law is correct, and the application is filed according to law, and the company is invited to give a detailed examination and grant a patent for invention.

The above is only the preferred embodiments of the present invention, and the scope of the present invention is not limited thereto, that is, the equivalent changes and modifications made by the scope of the invention and the contents of the invention are all It should remain within the scope of this invention.

Claims (11)

A microsphere granulation device based on spherical shape control, comprising: a feeding device, which is connected with a nozzle, the nozzle has an output end, and the output end sequentially defines a first segment and a second a feeding device for conveying a liquid heat sensitive material to the nozzle to form a liquid microsphere and outputting through the output end; and a cooling unit coupled to the second section and corresponding to the output end The cooling unit acts on the second section at a lower temperature than the freezing point of the heat sensitive material, so that the interface of the microsphere forms a rigid coating; the periphery of the nozzle is at least first-class Channel, the flow channel outputs a first medium, so that when the output end is output by each of the microspheres, the first medium is coated on the microsphere, and the first medium has a freezing point lower than a liquid material of the heat sensitive material, wherein the cooling unit acts on the second section at a lower temperature than a freezing point of the first medium, and the first medium is formed on the interface of the microspheres A rigid coating. The microsphere granulating device based on the spherical shape control according to claim 1, further comprising at least one side flow channel disposed in the first segment and corresponding to the output end, the side The flow channel outputs a second medium, the second medium is coated on the surface of the microsphere, and the second medium is a liquid or gaseous material having a freezing point lower than the heat sensitive material, and the cooling unit is Cooling at a temperature below the freezing point of the second medium acts on the second section such that the second medium forms a rigid coating on the interface of the microspheres. The microsphere granulating device based on the spherical shape control according to the second aspect of the invention, wherein the side channel is inclined at an inclination angle toward a moving direction of the microsphere. The microsphere granulation device based on the spherical shape control according to claim 1, further comprising a third segment corresponding to the end of the second segment, wherein the third segment is provided with a Corresponding to the collecting device of the output end, and the collecting device comprises a container containing the collecting liquid. The microsphere granulation device based on the spherical shape control according to the fourth aspect of the patent application further includes a cabin, the cabin is an insulated space, and the feeding device and the nozzle are disposed in the cabin At the top end, the cooling unit is disposed at a side end of the cabin, and the collecting device is disposed at a bottom end of the cabin. The microsphere granulation device based on the spherical shape control according to claim 1, further comprising a third segment corresponding to the end of the second segment, wherein the third segment is provided with a Corresponding to the collecting device of the output end, the collecting device comprises a container containing a collecting liquid, and the collecting liquid is a reaction liquid capable of generating a chemical reaction with the heat sensitive material, and the chemical reaction system is The surface of the heat sensitive material forms a coating film. The microsphere granulation device based on the spherical shape control according to claim 6, wherein the heat sensitive material comprises alginate, and the collected liquid comprises calcium chloride (CaCl ₂ ). The microsphere granulation device based on the spherical shape control according to claim 7, wherein the container is further provided with a heating device for heating the collection liquid to a temperature slightly higher than a freezing point of the heat sensitive material. The temperature of the person. The microsphere granulating device based on the spherical shape control according to the invention of claim 8, wherein the container further comprises a driving unit for causing the collecting liquid to generate a flow. The microsphere granulating device based on the spherical shape control according to the first aspect of the invention, wherein the cooling unit outputs a vortex airflow containing liquid nitrogen. The microsphere granulation device based on the spherical shape control according to the first aspect of the invention, wherein the feeding device is an injection device, and at least one corresponding to the heat sensitive material is disposed outside the feeding device. Thermostat.