TWI731660B - Processing method for accelerating the dispersion of injection-type fillers by means of pressurization - Google Patents

Abstract

The present invention provides a processing method for accelerating the dispersion of injection-type filling by means of pressurization, which comprises: accommodating a solvent and an injection-type filling in a first accommodation space and a second accommodation space respectively, and the injection-type filling contains a soluble Colloidal solute and insoluble dispersant; connect the first containment device, the connection device and the second containment device to each other; make the injection-type filler and the solvent form a mixture through the preliminary mixing step; and repeat the reciprocating pressure mixing step to make The flow rate of the mixture is increased and a shear force is formed to prevent the colloidal solutes or dispersoids in the injectable filling from aggregation, and to dissolve and disperse them in the solvent quickly and stably, respectively.

Description

Processing method for accelerating the dispersion of injection-type fillers by means of pressurization

The present invention relates to a processing method using pressure means to accelerate the dispersion of injection-type fillings, in particular to a processing method using back-and-forth pressure means to accelerate injection-type fillings used for medical cosmetology Of dispersion.

Injectable poly (D, L- lactic _{acid) (injectable poly- D, L -lactic} acid, PDLLA) is a new stimulation of collagen injectable fillers (injectable filler), may be filled in the soft tissue of the human body through injection, So as to achieve medical beauty effects such as wrinkle removal, contour modification or tissue plumping. The PDLLA filler contains PDLLA microspheres and hydroxymethyl cellulose (CMC). PDLLA microspheres are components used to stimulate collagen proliferation, but they are insoluble in injection solvents (for example, distilled water for injection). Hydroxymethyl cellulose is a water-soluble polymer that can become a colloidal solution when dissolved in a solvent for injection, which has the effect of increasing viscosity, providing dispersion and suspension, etc., so that PDLLA microspheres can be well dispersed and suspended in the injection In addition, the injection solution containing hydroxymethyl cellulose has a certain viscosity and can be better retained in the target tissue after injection without transferring to other tissues.

PDLLA fillers gradually stimulate the proliferation of collagen to achieve medical cosmetic effects. Compared with the traditional direct injection of hyaluronic acid or collagen, the medical cosmetic effects can be more natural and lasting. However, in the state of being formulated as a solution for injection, the PDLLA microspheres are gradually decomposed into lactic acid due to hydrolysis, and the hydroxymethyl cellulose hydrogel (CMC hydrogel) will also be gradually hydrolyzed. Therefore, the PDLLA filling needs to be stored by freeze-drying after the preparation is completed, and the injection solvent is used for reconstitution before use.

In the above reduction step, the injection solvent is usually added to a sample bottle containing freeze-dried PDLLA filling, and the sample bottle is sealed or transferred to a centrifuge tube (or microcentrifuge tube) for mixing. Traditionally, mixing methods are divided into hand-shaking method and vortex method. In the case where the required filler concentration is low, for example, in the case of reducing 200 mg of PDLLA filler with 8 mL of solvent, the hand shake method can be used for mixing, but it often takes more than 30 minutes Zhong can mix it evenly. In addition, when the required filler concentration is high, for example, when 200 mg of PDLLA filler is reduced with 1.4 mL of solvent, it is more suitable to use the vortex method for mixing. That is, a sample bottle or centrifuge tube filled with a filler and a solvent is placed on an oscillation platform of a vortex generator and then pressed down, and the liquid is vortexed at a rotation speed of 2700 rpm to assist mixing. However, in the case of the above-mentioned high concentration, even if the mixing is carried out by the vortex method, it takes more than 1 hour to mix it uniformly.

Moreover, the disadvantage of the above-mentioned traditional method of using hand-crank method or vortex method is that even if the vortex method generates a higher shear force on the fluid than the hand-crank method, it accelerates and enhances the PDLLA filler. The dispersing speed and effect of solvent reduction are still quite time-consuming, and after being evenly dispersed, after standing for 30 minutes, there will still be a phenomenon of separation between the solvent and the filler (as shown in Figure 13), making the traditional temporary use The conditions of use of the formulation method are more stringent. For similar injectable poly(L-lactic acid) (injectable PLLA) products (including PLLA, CMC and mannitol), it takes 48 hours to evenly disperse.

A filler solution for injection that cannot be uniformly dispersed will not only cause uneven medical beauty effects of the target tissue, but also may cause complications such as papules and nodules due to the aggregation of the filler.

In view of the above problems, there is a need for a processing method that uses pressurization to accelerate the dispersion of injection-type fillings. Compared with the vortex generator, it can provide greater shear force, so as to prevent the injection-type filling from gathering and shorten the injection-type filling. It takes time to disperse the filler, and can improve its dispersion effect and stability.

The present invention provides a processing method for accelerating the dispersion of injection-type fillings by means of pressurization, which includes the steps of providing a first containing device, a second containing device and a connecting device, wherein the first containing device has a A first accommodating space, the second accommodating device has a second accommodating space, and the connecting device has a communicating channel whose cross-sectional area is smaller than the cross-sectional area of the first accommodating device and the cross-sectional area of the second accommodating device Accommodating step, accommodating a solvent in the first accommodating space, and accommodating an injectable filler in the second accommodating space, the injectable filler containing colloidal solute soluble in the solvent and insoluble in the solvent Dispersing substance; connecting step, connecting the first containing device with the second containing device through the connecting device, so that the first containing space, the channel, and the second containing space are in communication with each other; the preliminary mixing step is for the first The solvent in the accommodating space is pressurized to partially or completely squeeze the solvent into the second accommodating space, so that the injection-type filling and the solvent form a mixture; and the reciprocating pressure mixing step includes: The mixture in the second accommodating space is pressurized to partially or completely squeeze the mixture into the first accommodating space, and then the mixture in the first accommodating space is pressurized to partially or completely Squeezed into the second containing space; wherein, by repeating the reciprocating pressure mixing step, the flow rate of the mixture is increased and a shear force is formed to prevent the colloidal solute or the dispersed substance from gathering, thereby making the colloidal solute uniform It is dissolved in the solvent, and the dispersoid in the injectable filling is uniformly dispersed in the solvent.

Preferably, the total time of the reciprocating pressure mixing step is 30 seconds or less.

According to an embodiment of the present invention, in the accommodating step, the part of the second accommodating space other than the injectable filling also contains the first air, and in the preliminary mixing step and the reciprocating adding The pressure mixing step further includes: an air removal step, separating the first accommodating device from the connecting device, and blocking external air from entering the first accommodating space; and pressurizing the mixture in the second accommodating space Thereby, the first air in the second accommodating space is discharged through the passage of the connecting device; then, the first accommodating device is connected to the connecting device again.

According to an embodiment of the present invention, in the containing step, the injectable filler has a flocculent structure, including a surface layer portion and an inner core portion, and the inner core portion further contains second air; in the preliminary mixing step In this case, the solvent infiltrates the surface part of the injectable filling and forms a gas-liquid interface with the second air in the inner core part of the injectable filling, thereby forming a bubble in the gas-liquid interface, and the second The air and the core part of the injectable filler are contained in the bubble; and in the reciprocating pressure mixing step, the flow rate of the mixture is increased by pressurizing the mixture to form a shear force to destroy the Air bubbles, so that the solvent enters the air bubbles, so that the colloidal solute in the inner core part of the injectable filling is uniformly dissolved in the solvent, and the inner core part of the injectable filling The dispersant is uniformly dispersed in the solvent.

Preferably, the first accommodating device has an adjustable first accommodating space, and the second accommodating device has an adjustable second accommodating space.

Preferably, in the preliminary mixing step, the solvent in the first accommodating space is pressurized by reducing the volume of the first accommodating space.

Preferably, in the reciprocating pressure mixing step, the mixture in the second accommodating space is pressurized by reducing the volume of the second accommodating space, and the mixture in the second accommodating space is reduced by reducing the volume of the first accommodating space. The mixture in the first containing space is pressurized.

Preferably, in the air removal step, the mixture in the second accommodating space is pressurized by reducing the volume of the second accommodating space.

According to an embodiment of the present invention, the dispersant includes at least one selected from the group consisting of: poly(D,L-lactic acid) (PDLLA); poly(L-lactic acid) (PLLA); polycaprolactone (PCL); Hyaluronic acid (HA); Hydroxyapatite (HAP); and Collagen.

According to an embodiment of the present invention, the colloidal solute includes at least one selected from the group consisting of: carboxymethyl cellulose (CMC); hyaluronic acid (HA); and hyaluronic acid (HA) and calcium phosphate (TCP) mixture.

According to an embodiment of the present invention, the solvent includes at least one selected from the group consisting of: sodium bicarbonate (sodium bicarbonate) aqueous solution; sterile water for injection (SWFI); normal saline (normal saline); lidocaine (lidocaine, anesthetic); lidocaine with epinepbrine (lidocaine+E); and mannitol.

According to an embodiment of the present invention, the dispersion is porous microspheres.

In summary, in the processing method of the present invention that uses pressure to accelerate the dispersion of injection-type fillers, the total time of the reciprocating pressure mixing step is less than 30 seconds to achieve the effect of uniformly dispersing the injection-type filler. Compared with the prior art, it takes 20 minutes to 48 hours to have a significant improvement effect.

In addition, by using the treatment method of the present invention to disperse the injection-type filler, the uniform dispersion effect is maintained even after being allowed to stand for 30 minutes after being uniformly dispersed, and the dispersion stability is improved.

In addition, the injectable filler dispersed by the processing method of the present invention does not cause aggregation of the injectable filler regardless of the dispersing effect of the solvent. In addition, the dispersion effect in the solvent with the best dispersion effect is also better than that of the prior art, which also proves that the present invention has a significant improvement effect in dispersing injection-type fillings.

In the following description of the present invention, a detailed description of the prior art will be omitted to the extent that a person with ordinary knowledge in the relevant technical field can easily understand it.

As shown in Figure 1, the processing method of the present invention for accelerating the dispersion of injection-type fillers by means of pressurization includes: providing step S10, containing step S20, connecting step S30, preliminary mixing step S40, air removal step S50, reciprocating adding Press mixing step S60. The present invention will be described in detail below.

2, in the providing step S10, the first accommodating device 10, the second accommodating device 20, and the connecting device 30 are prepared. Among them, the first accommodating device 10 and the second accommodating device 20 respectively have a first accommodating space 11 and a second accommodating space 21 with adjustable volumes, and the connecting device 30 has a communicating channel (refer to FIG. 3 ). Wherein, the cross-sectional area of the channel of the connecting device 30 is smaller than the cross-sectional area of the first containing device 10 and the second containing device 20, so that the smaller cross-sectional area can be used for the solvent 40 or the solvent 40 and the injection in the subsequent steps. The mixture of formula filling 50 is pressurized.

Preferably, the first accommodating device 10 and the second accommodating device 20 can be syringes, the pistons of which can be used to adjust the volume of the first accommodating space 11 and the second accommodating space 21, and these syringes have respective connection devices The openings of the channels of 30 are matched for connecting to the channels of the connecting device 30 respectively.

Next, in the accommodating step S20, the solvent 40 is added to the first accommodating space 11, and the injectable filler 50 is added to the second accommodating space 21. The injectable filler 50 contains a colloidal solute 52 that is soluble in the solvent 40 and The dispersoid 51 which is insoluble in the solvent 40 (refer to FIG. 6).

Injectable fillers 50 may be an injection of Poly (D, L- lactic _{acid) (injectable poly- D, L -lactic} acid), which is a method for stimulating collagen medical cosmetic products.

The solvent 40 may be, for example, an aqueous solution of sodium bicarbonate (sodium bicarbonate), distilled water for injection (sterile water for injection, SWFI), normal saline (normal saline), lidocaine (lidocaine, anesthetic), and epinephrine-containing Lidocaine with epinephrine (lidocaine + E) or mannitol, preferably distilled water for injection (SWFI).

The dispersant 51 can be, for example, poly(D,L-lactic acid) (poly- _D,L- lactic acid, PDLLA), poly(L-lactic acid) (PLLA), polycaprolactone (PCL), hyaluronic acid (HA) , Hydroxyapatite (HAP) or Collagen (Collagen), preferably poly(D,L-lactic acid) (PDLLA).

The dispersant 51 may be a porous microsphere with a high-density surface structure and a hollow internal structure.

The colloidal solute 52 may be, for example, carboxymethyl cellulose (CMC), hyaluronic acid (HA), or a mixture of hyaluronic acid (HA) and calcium phosphate (tricalcium phosphate, TCP), preferably carboxymethyl cellulose (CMC), hyaluronic acid (HA). Methyl cellulose (CMC).

Then, in the connecting step S30, the first accommodating device 10 is connected to the second accommodating device 20 through the connecting device 30, so that the first accommodating space 11, the passage of the connecting device 30, and the second accommodating space 21 are communicated with each other.

3, in an embodiment, the connecting device 30 may be a three-way valve with three passages 30b, 30c, 30d, and a valve 30a for controlling the communication state of the three passages 30b, 30c, 30d. Preferably, two adjacent (that is, right-angled) channels 30b, 30c or 30c, 30d can be used to connect to the first containment device 10 and the second containment device 20, respectively, so that the reciprocating pressure mixing step S60 , The angle of the two hands respectively operating the first containing device 10 and the second containing device 20 is 90 degrees, which is more ergonomic.

4, in another embodiment, the connecting device 30 can be replaced with an L-shaped tube 31 having two channels 31a, 31b. Alternatively, the connecting device 30 can be replaced with a V-shaped tube (not shown in the figure). Preferably, the channel of the V-shaped tube can be composed of two branch channels with an included angle of 60 degrees to 120 degrees, so that the reciprocating pressure mixing step The S60 is more ergonomically designed, and it is better to have a 90-degree angle, that is, an L-shaped tube.

Next, referring to FIG. 2, in the preliminary mixing step S40, the piston of the first containing device 10 is pressurized along the A direction to reduce the volume of the first containing space 11, thereby adding the solvent 40 in the first containing space 11 Press to partially or completely squeeze the solvent 40 into the second accommodating space 21, so that the injectable filler 50 and the solvent 40 form a mixture (as shown in FIG. 5).

Since in the accommodating step S20, the part of the second accommodating space 21 other than the injection-type filler 50 is also accommodating air (as shown in FIG. 2, hereinafter referred to as the first air 60), therefore, in the preliminary After the mixing step S40, an air removal step S50 may be further performed to remove the first air 60.

The reason for performing the air removal step S50 is that if there is a large amount of air in the communication space of the first accommodating space 11, the passage of the connecting device 30, and the second accommodating space 21, the air will occupy a large amount of space in the communication space. In addition, an air pressure (about 1 atmosphere) is formed, which is not conducive to the subsequent reciprocating pressure mixing step S60.

As shown in FIG. 7, in the air removal step S50, the first accommodating device 10 is separated from the connecting device 30, and the volume of the first accommodating space 11 is fixed through (that is, the piston position of the first accommodating device 10 is kept unchanged) To block external air from entering the first accommodating space 11; and pressurize the piston of the second accommodating device 20 along the C direction to reduce the volume of the second accommodating space 21, thereby adding to the mixture in the second accommodating space 21 Press to discharge the first air 60 in the second accommodating space 21 through the channel 30c of the connecting device 30; then, the first accommodating device 10 is reconnected with the connecting device 30 (as shown in FIG. 9).

Or, as shown in FIG. 8, the first accommodating device 10 and the connecting device 30 may not be separated, but the valve 30a of the connecting device 30 may be converted to connect the second accommodating space 21 with the outside, and closing the first accommodating space 11 and the second accommodating space 21 channel. Therefore, it is also possible to pressurize along the C direction while blocking the entry of external air into the first accommodating space 11 to discharge the first air 60 in the second accommodating space 21 from the passage 30d of the connecting device 30, and then the valve 30a is turned back to the state shown in FIG. 9 to reconnect the first receiving device 10.

Finally, in the reciprocating pressurization and mixing step S60, first, referring to FIG. 9, continue to pressurize the piston of the second accommodating device 20 along the C direction to reduce the volume of the second accommodating space 21, thereby increasing the volume of the second accommodating space 21. Pressurize the mixture to partially or completely squeeze the mixture into the first accommodating space 11; then, referring to FIG. 10, pressurize the piston of the first accommodating device 10 again along the A direction to reduce the first accommodating space 11 to pressurize the mixture in the first accommodating space 11 to partially or completely squeeze the mixture into the second accommodating space 21. Wherein, by repeating the reciprocating pressure mixing step S60, the flow rate of the mixture in the communicating first containing space 11 and the second containing space 21 is increased and a shear force is formed to prevent the colloidal solute 52 or the dispersoid 51 from gathering, thereby making The colloidal solute 52 in the injection-type filling 50 is uniformly dissolved in the solvent 40, and the dispersoid 51 in the injection-type filling 50 is uniformly dispersed in the solvent 40.

Refer to FIG. 6, which is a partial enlarged schematic view of part 5A of FIG. 5. According to an embodiment of the present invention, in the accommodating step S20, the injection-type filler 50 has a flocculent structure and includes a surface layer part (from the boundary B to the boundary B'in FIG. 6) and an inner core part (as shown in FIG. 6). The part within the boundary B'), and the inner core part also contains the second air 70; in the preliminary mixing step S40, the solvent 40 infiltrates the surface part of the injection-type filling 50 to cause the surface part of the injection-type filling 50 to swell Wet (such as the boundary B'to the boundary B"), and the solvent 40 also forms a gas-liquid interface with the second air 70 in the inner core portion (such as the boundary B'), thereby forming in the gas-liquid interface B' The bubble, that is, the air-liquid interface B'is the surface of the bubble, and the second air 70 and the inner core portion of the injectable filler 50 are contained in the bubble; and, in the reciprocating pressure mixing step S60, the mixture The pressure is applied to increase the flow rate of the mixture and form a shearing force to break the bubbles, so that the solvent 40 enters the bubbles, so that the colloidal solute 52 in the inner core portion of the injectable filler 50 is uniformly dissolved in the solvent 40 , And the dispersoid 51 in the inner core portion of the injection-type filler 50 is uniformly dispersed in the solvent 40, thereby forming a uniform dispersion 80.

Since the surface tension of the gas-liquid interface B'of the bubbles prevents the solvent 40 from uniformly mixing with the injectable filler 50, it is necessary to accelerate the mixing by destroying the gas-liquid interface B'of the bubbles.

Preferably, the total execution time of the reciprocating pressure mixing step S60 of the present invention is less than 30 seconds to achieve the effect of uniformly dissolving the colloidal solute 52 and uniformly dispersing the dispersing substance 51 (as shown in FIG. 11, which is shown in FIG. 5). The partial enlarged schematic diagram of the part 5A after repeating the reciprocating pressure mixing step S60), which has a significant improvement effect compared to the prior art, which takes 20 minutes to 48 hours.

As shown in Figure 12, select 4 common solvents for injection: distilled water for injection (SWFI), normal saline (NS), lidocaine (lidocaine), lidocaine with epinephrine (lidocaine+E); And two solvents for comparison: sodium bicarbonate (NaHCO ₃ ) aqueous solution with strong ionic strength, and mannitol as a strong osmotic dehydrating agent. Each of the above 6 solvents was used to infiltrate one injection-type filling 50 in 3 minutes. Without external stirring, SWFI and mannitol have a better dispersion effect due to their weakest ionic strength, because stronger ionic strength will cause more aggregation.

In order to further verify the dispersion effect of the treatment method of the present invention, using the treatment method of the present invention, two 3mL syringes were added with 200mg of injectable filler and 8mL of solvent respectively, and a three-way valve was used to connect the two syringes. Then through the back-and-forth pressure mixing method, the mixture in the syringe is repeatedly pushed between the two syringes for 1 minute, and it only takes less than 30 seconds to achieve uniform dispersion. The results are shown in Figure 15 and Figure 16. Figure 15 is a photograph of the dispersion state of the injection-type filling after being dispersed in various solvents for 1 minute using the reciprocating pressure mixing method and then standing for 30 minutes. 16 is a photomicrograph of the dispersion state of the injection-type filling after being dispersed in various solvents for 1 minute using the reciprocating pressure mixing method.

In addition, using the vortex method as a control, 200 mg of syringe filling and 8 mL of solvent were added to a 2 mL microcentrifuge tube, and then placed on the shaking platform of a general vortex generator and pressed down to generate a vortex at 2700 rpm. The mixture in the tube was dispersed for 30 minutes, and the results are shown in Figs. 13 and 14. Fig. 13 is a photograph of the dispersion state of the injection-type filling after being dispersed in various solvents for 30 minutes using the vortex method and then standing for 30 minutes, and Fig. 14 is the dispersion state of the injection-type filling material being dispersed in various solvents by the vortex method 30 Photomicrograph of the dispersion pattern after minutes.

Referring to Figure 15, it can be seen that by using the processing method of the present invention to disperse the injection-type filling, even after being allowed to stand for 30 minutes after being uniformly dispersed, the injection-type filling in various solvents remains uniformly dispersed without being mixed with the solvent. In contrast to this, in the prior art, the injection-type filler and the solvent layered (as shown in Figure 13) after being allowed to stand for 30 minutes after being processed by the vortex generator. The present invention has good dispersion stability and has Very significant improvement effect.

And, referring to FIG. 16, FIG. 16 is a photomicrograph taken after uniform dispersion of the injection-type filling dispersed by using the processing method of the present invention (the left and right images use SWFI and NS respectively as solvents). It can be seen that no matter in the SWFI solvent with the best dispersion effect or in the NS with poor dispersion effect, the injection-type filler (the black dot in Figure 16) does not produce aggregation. In contrast, the prior art uses vortex The injection-type filler processed by the generator has serious aggregation in the NS solvent with poor dispersion effect (as shown in the right picture of Fig. 14), and the dispersion effect of the SWFI solvent with the best dispersion effect (as shown in the left picture of Fig. 14) It is not as uniform as the present invention, and it also proves that the present invention has a significant improvement effect in dispersing injectable fillings.

In summary, the processing method of the present invention that uses pressurization to accelerate the dispersion of injection-type fillers, through the use of a back-and-forth pressurization method, provides greater than the traditional manual or vortex generation method The shear force is sufficient to prevent the aggregation of colloidal solutes or dispersants in the injection-type filling, and can destroy the bubbles formed by the air in the injection-type filling, so as to produce a good dispersion effect in a short time, and the dispersion is evenly dispersed. After maintaining good stability.

10: The first containment device

11: The first accommodation space

20: second containment device

21: second accommodation space

30: Connect the device

30a: Valve

30b: Channel

30c: Channel

30d: channel

31: L-shaped tube

31a: Channel

31b: Channel

40: Solvent

5A: Part

50: Injectable filler

51: Dispersion

52: colloidal solute

60: First Air

70: second air

80: dispersion

A: Direction

B: boundary

B’: boundary, gas-liquid interface

B’’: boundary

C: direction

S10: Provide steps

S20: containment step

S30: Connection steps

S40: Preliminary mixing steps

S50: Air removal step

S60: Reciprocating pressure mixing step

Fig. 1 is a flow chart of the processing method for accelerated injection-type filling dispersion of the present invention; Fig. 2 is a schematic diagram of the accommodating step device of the present invention; Fig. 3 is a schematic diagram of an embodiment of the connecting device of the present invention; Fig. 4 is the present invention Figure 5 is a schematic diagram of the preliminary mixing step of the present invention; Figure 6 is a partial enlarged view of the bubbles in the preliminary mixing step of Figure 5; Figure 7 is the air removal step of the present invention A schematic diagram of an embodiment; Figure 8 is a schematic diagram of another embodiment of the air removal step of the present invention; Figure 9 is a schematic diagram of the reciprocating pressure mixing step of the present invention, in which the volume of the second containing device is reduced to correct The mixture is pressurized; Figure 10 is a schematic diagram of the reciprocating pressure mixing step of the present invention, in which the mixture is pressurized by reducing the volume of the first containing device; Figure 11 is the bubble in Figure 5 after reciprocating Partial enlarged view after the pressure mixing step; Figure 12 is a photo of the dispersion state of the injection-type filling after being soaked in various solvents for 3 minutes; Figure 13 is the use of a vortex generator to uniformly disperse the injection-type filling in various solvents Then, it is a photo of the dispersion state after being allowed to stand for 30 minutes; Figure 14 is a photomicrograph of the dispersion state in which the injection-type filler is uniformly dispersed in various solvents using a vortex generator; Figure 15 is a photomicrograph of the dispersion state using the processing method of the present invention The injection-type filler is uniformly dispersed in various solvents and then is a photograph of the dispersion state after being allowed to stand for 30 minutes; and Figure 16 shows the dispersion state of the injection-type filler uniformly dispersed in various solvents using the processing method of the present invention. Micro photos.

S10: Provide steps

S20: containment step

S30: Connection steps

S40: Preliminary mixing steps

S50: Air removal step

S60: Reciprocating pressure mixing step

Claims (9)

A processing method for accelerating the dispersion of injection-type fillings by means of pressurization includes the steps of providing a first containing device, a second containing device and a connecting device, wherein the first containing device has a first containing device. The second accommodating device has a second accommodating space, and the connecting device has a communicating channel, the cross-sectional area of the channel is smaller than the cross-sectional area of the first accommodating device and the cross-sectional area of the second accommodating device; the accommodating step Accommodating a solvent in the first accommodating space, and accommodating an injectable filler in the second accommodating space, the injectable filler comprising a colloidal solute that is soluble in the solvent and a dispersant that is insoluble in the solvent; In the connecting step, the first accommodating device is connected to the second accommodating device through the connecting device, so that the first accommodating space, the passage, and the second accommodating space communicate with each other; the preliminary mixing step is to connect the first accommodating space to the first accommodating space. The solvent is pressurized to partially or completely squeeze the solvent into the second accommodating space, so that the injection-type filling and the solvent form a mixture; and the reciprocating pressure mixing step includes: the second accommodating space The mixture in the accommodating space is pressurized to partially or completely squeeze the mixture into the first accommodating space, and then the mixture in the first accommodating space is pressurized to partially or completely squeeze the mixture into In the second containing space; wherein, by repeating the reciprocating pressure mixing step, the flow rate of the mixture is increased and a shear force is formed to prevent the colloidal solute or the dispersoid from gathering, so that the colloidal solute is uniformly dissolved in the In the solvent, and the dispersant is uniformly dispersed in the solvent; wherein in the containing step, the portion of the second containing space other than the injection-type filling is also contained in the first air, and , Between the preliminary mixing step and the reciprocating pressure mixing step, further comprising: an air removal step, separating the first containing device from the connecting device, and blocking outside air from entering the first containing space; and The mixture in the second accommodating space is pressurized to exhaust the first air in the second accommodating space through the passage of the connecting device; then, the first accommodating device is reconnected with the connecting device. Such as the processing method of claim 1, wherein the total execution time of the reciprocating pressure mixing step is 30 seconds or less. According to the processing method of claim 1, wherein, in the containing step, the injection-type filling has a flocculent structure, including a surface layer portion and an inner core portion, and the inner core portion further contains a second air; in the In the preliminary mixing step, the solvent infiltrates the surface part of the injectable filling and forms a gas-liquid interface with the second air in the inner core part of the injectable filling, thereby forming a bubble in the gas-liquid interface, The second air and the inner core portion of the injection-type filling are contained in the bubble; and in the reciprocating pressure mixing step, the flow rate of the mixture is increased by pressurizing the mixture and a shear force is formed To destroy the bubble, so that the solvent enters the bubble, so that the colloidal solute in the inner core portion of the injectable filling is uniformly dissolved in the solvent, and the inner core of the injectable filling The dispersoid in the part is uniformly dispersed in the solvent. Such as the processing method of claim 1, wherein the first accommodating device has an adjustable first accommodating space, and the second accommodating device has an adjustable second accommodating space; in the preliminary mixing step, by reducing The volume of the first accommodating space is used to pressurize the solvent in the first accommodating space; and in the reciprocating pressure mixing step, the volume of the second accommodating space is reduced to reduce the volume of the second accommodating space. The mixture is pressurized, and the mixture in the first accommodation space is pressurized by reducing the volume of the first accommodation space. Such as the processing method of claim 1, wherein the first accommodating device has an adjustable first accommodating space, and the second accommodating device has an adjustable second accommodating space; in the preliminary mixing step, by reducing The volume of the first accommodating space is used to pressurize the solvent in the first accommodating space; in the air removal step and the reciprocating pressure mixing step, the second accommodating space is reduced by reducing the volume of the second accommodating space. The mixture in the accommodating space is pressurized; and in the reciprocating pressure mixing step, the mixture in the first accommodating space is pressurized by reducing the volume of the first accommodating space. The processing method according to any one of claims 1 to 5, wherein the dispersoid comprises at least one selected from the group consisting of: poly(D,L-lactic acid) (PDLLA); poly(L-lactic acid) ) (PLLA); polycaprolactone (PCL); hyaluronic acid (HA); hydroxyapatite (HAP); and collagen (Collagen). The processing method according to any one of claims 1 to 5, wherein the colloidal solute comprises at least one selected from the group consisting of: carboxymethyl cellulose (CMC); hyaluronic acid (HA); and hyaluronic acid ( A mixture of HA) and calcium phosphate (TCP). The processing method according to any one of claims 1 to 5, wherein the solvent comprises at least one selected from the group consisting of: sodium bicarbonate (sodium bicarbonate) aqueous solution; sterile water for injection (sterile water for injection, SWFI); normal saline (normal saline); lidocaine (lidocaine, anesthetic); lidocaine with epinephrine (lidocaine+E); and mannitol (mannitol). The processing method according to any one of claims 1 to 5, wherein the dispersion is porous microspheres.

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