Freeze-drying structure capable of inducing nucleation through ultrasonic oscillation and pre-freezing method

Abstract

The invention relates to a freeze-drying structure capable of inducing nucleation through ultrasonic oscillation and a pre-freezing method, the freeze-drying structure comprises a shelf with a heat-conducting oil inlet and a heat-conducting oil outlet, and an ultrasonic generator is arranged on the shelf. The ultrasonic vibration is introduced in the pre-freezing stage to promote nucleation of the material reaching the freezing equilibrium temperature, no foreign substance is introduced as a nucleation inducer in the implementation process, ice mist is not required to be introduced to induce the freezing process, and the operation of controlling pressure increase or pressure reduction is not required; the nucleation process is adjusted by controlling the temperature of the materials on the shelf and the vibration frequency of the shelf, so that the materials form ice crystals with proper sizes in the freezing process, the sublimation speed of the materials is reasonably controlled, and a complete freeze-drying appearance is formed.

Description

Technical Field

[0001] The invention relates to the technical field of freeze drying, and in particular to a freeze drying structure and a pre-freezing method for inducing nucleation through ultrasonic oscillation. Background Art

[0002] Freeze drying is a drying process mainly used in the vaccine and biopharmaceutical industries. It removes moisture from materials through low-temperature sublimation, which can effectively reduce the loss of bioactive substances in materials and extend the storage time of materials. The freeze drying process is divided into three stages: freezing, sublimation, and drying. The change process of the material in the freezing stage determines the shape of the ice crystals after solidification. The ice crystals will leave pores in the sublimation stage. The size and number of pores determine the sublimation resistance of sublimation, drying, and analytical drying. The freezing step determines the shape and size distribution of ice crystals after freezing, affecting the product drying rate, product crystallinity, and surface area of ​​the freeze-dried product.

[0003] During the freezing process, the phenomenon that the liquid is not frozen below the equilibrium freezing point of the solution is called supercooling. The difference between the equilibrium ice formation temperature and the actual temperature when the ice crystals first form is called supercooling. Ice crystals are formed randomly during the freezing stage. The number of ice nuclei formed, the growth rate of ice, and the size of ice crystals depend on the supercooling. The higher the supercooling, the lower the nucleation temperature, which will lead to a high nucleation rate and the formation of a large number of small ice crystals. The ice crystals after freezing will sublimate in the subsequent primary drying process, leaving pores of similar size.

[0004] Under normal circumstances, during the freezing stage of the material, the shelf first cools the vial. Since the shelf and the vial are only in contact at the bottom, heat transfer can only be transferred upward from the bottom, resulting in nucleation at the bottom of the vial material first, while the upper layer of the material has not yet reached the nucleation temperature, resulting in uneven freezing in the bottle. The uneven freezing of ice crystals leads to uneven pore sizes after ice crystal sublimation, which affects the sublimation rate. Due to different positions, the heating conditions at the bottom of the vials on the same shelf are also inconsistent, which leads to differences between bottles on the same shelf. In order to achieve uniform nucleation of the material, the nucleation conditions during the pre-freezing process must be controlled. Therefore, there is a method of introducing foreign substances into the vial and directly contacting the material as a nucleating agent, such as ice mist, silver iodide, etc., which increases the risk of bacterial contamination and introduction of foreign matter. Furthermore, there is also a method of applying low temperature, decompression, and pressurization to the material through physical and chemical properties to promote material nucleation, but its operation is complicated, control is difficult, and there is a risk of low-temperature boiling. Summary of the invention

[0005] The purpose of the present invention is to overcome the deficiencies of the prior art and provide a freeze-dried structure and a pre-freezing method for inducing nucleation through ultrasonic oscillation.

[0006] To achieve the above object, the present invention adopts the following technical solutions: A freeze-drying structure for inducing nucleation through ultrasonic oscillation comprises a shelf with a heat transfer oil inlet and a heat transfer oil outlet, an ultrasonic generator is arranged on the shelf; a conduction plate is fixed on the top of the shelf, and the ultrasonic generator is located on the top of the conduction plate.

[0007] A freeze-drying structure that induces nucleation through ultrasonic oscillation comprises a shelf with a heat transfer oil inlet and a heat transfer oil outlet, wherein an ultrasonic generator is arranged on the shelf; the shelf comprises an upper shelf, wherein the ultrasonic generator is embedded in the bottom of the upper shelf; a shelf vertical extension section and a baffle are arranged on the periphery of the top of the upper shelf, wherein the shelf vertical extension section and the baffle are enclosed at the top of the upper shelf to form a water tank, and the shelf vertical extension section is connected with a heat transfer oil inlet pipe and a heat transfer oil outlet pipe.

[0008] Furthermore, the shelf also includes a lower shelf connected and fixed below the upper shelf.

[0009] Furthermore, the upper shelf and the lower shelf are fixed by bolt connection or welding.

[0010] Furthermore, the water tank is connected to a water supply device, which includes a water storage tank, and the water outlet end of the water storage tank is connected to the inside of the water tank through a stop valve and a pipeline.

[0011] Furthermore, a liquid level meter is provided on the vertical extension section of the shelf.

[0012] Furthermore, a transparent observation section is provided on the vertical extension section of the shelf.

[0013] Furthermore, two ends of the baffle are fixed to the opening of the vertical extension section of the shelf by bolt connection.

[0014] The pre-freezing method using the above-mentioned freeze-drying structure begins by filling water into the water tank on the top of the upper shelf, with the liquid level not higher than the height of the vial material; then the water temperature in the water tank is lowered by the heat transfer oil in the upper shelf, thereby forming a uniform cooling environment around the vial, so that the temperature of the material in the vial is lowered; after the water tank temperature reaches the equilibrium freezing temperature, the ultrasonic generator is turned on to transmit the ultrasonic oscillation to the vial through the upper shelf, inducing nucleation, so that the material in the vial is evenly frozen.

[0015] By adopting the above technical solution, the present invention has the following beneficial effects: 1. By introducing ultrasonic vibration in the pre-freezing stage, the nucleation of the material reaching the freezing equilibrium temperature is promoted. During the implementation process, no foreign substances are introduced as nucleation inducers, no ice fog is introduced to induce the freezing process, and no pressure increase or pressure reduction operation is required. The nucleation process is adjusted by controlling the temperature of the material on the shelf and the shelf vibration frequency, so that the material forms ice crystals of appropriate size during the freezing process, and the sublimation material speed is reasonably controlled to form a complete freeze-dried appearance; 2. By adding an ultrasonic transducer at the bottom of the upper shelf and a vertical extension section of the shelf set on the upper shelf, water is used as a medium for heat transfer and vibration transmission to achieve temperature control of the environment around the bottle body, changing the previous way of temperature transmission from the shelf to the bottom of the bottle. Due to the presence of water as a medium, the temperature around the bottle body is uniform, and the temperature of the material at each point in the bottle is more uniform than before. At the equilibrium freezing temperature, applying ultrasonic oscillations can easily induce nucleation uniformly in the bottle. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] The present invention is further described in detail below with reference to the accompanying drawings and specific embodiments: Figure 1 It is a front view of embodiment 1 of the present invention; Figure 2 It is a front view of embodiment 2 of the present invention; Figure 3 It is a top view of embodiment 3 of the present invention. DETAILED DESCRIPTION

[0017] like Figure 1 As shown in Example 1, the present invention is a freeze-drying structure that induces nucleation by ultrasonic oscillation, including a shelf 11 with a heat transfer oil inlet and a heat transfer oil outlet, and an ultrasonic generator 12 is provided on the shelf 11; a conductive plate 13 is fixed to the top of the shelf 11, and the ultrasonic generator 12 is located on the top of the conductive plate 13.

[0018] In Example 1, a conductive plate 13 having the same size as the shelf 11 is provided, an ultrasonic generator 12 is installed on the top of the conductive plate 13, and the ultrasonic generator 12 can adjust the power. The conductive plate 13 is installed above the shelf 11 of the freeze dryer, and the conductive plate 13 is close to the upper wall of the shelf 11 and fixed with bolts. During the pre-freezing process, the heat transfer oil circulating in the shelf 11 is responsible for cooling the material in the vial to the equilibrium freezing temperature. The conductive plate 13 has two functions: one is to transfer the temperature of the shelf 11 to the bottom of the bottle so that the material in the vial reaches the equilibrium freezing temperature, and the other is to transfer the vibration generated by the ultrasonic vibrator to the vial so that the vial is completely frozen at the equilibrium freezing temperature.

[0019] like Figure 2-3 As shown, Example 2 optimizes the setting of the shelf and the ultrasonic generator on the basis of Example 1, and removes the conduction plate above the shelf. The existence of the conduction plate affects the heat conduction efficiency. Although the conduction plate and the shelf are tightly fitted, there is still a gap, resulting in uneven heat transfer. Due to the vibration of the conduction plate, there is a slight friction between the conduction plate and the shelf, which may produce fine powder after long-term operation, resulting in a high particle content on the shelf, introducing risks.

[0020] The conduction plate above the shelf is removed, and the vibration component of the ultrasonic generator is installed below the shelf instead of on the conduction plate. The advantage of removing the conduction plate is that the shelf can directly supply heat to the bottom of the bottle, thereby improving the heat transfer efficiency. There is no vibration and friction between the shelf and the conduction plate, and the generation of tiny particles is eliminated. The ultrasonic transducer is installed inside the shelf. Specifically, the freeze-drying structure of Example 2 includes a shelf having a heat transfer oil inlet and a heat transfer oil outlet, and an ultrasonic generator 22 is provided on the shelf; the shelf includes an upper shelf 21, and the ultrasonic generator 22 is embedded in the bottom of the upper shelf 21; a shelf vertical extension section 23 and a baffle 24 are provided on the periphery of the top of the upper shelf 21, and the shelf vertical extension section 23 and the baffle 24 are enclosed at the top of the upper shelf 21 to form a water tank, and the shelf vertical extension section 23 is connected with a heat transfer oil inlet pipe and a heat transfer oil outlet pipe to ensure that the heat transfer oil can fully flow through the shelf vertical extension section 23, so that the peripheral heat radiation does not affect the material in the vial on the shelf.

[0021] The shelf also includes a lower shelf 25 connected and fixed below the upper shelf 21. The upper shelf 21 and the lower shelf 25 can be fixed by bolt connection, welding or other fixing methods.

[0022] During pre-freezing and cooling, both the upper shelf 21 and the lower shelf 25 are conducted with heat transfer oil. The existence of the lower shelf 25 is to compensate for the temperature of the vials below the lower shelf 25 (the next layer) during the freeze-drying process. Another function is to keep the lower part of the shelf flat after the installation of the ultrasonic transducer, which is conducive to plugging after freeze-drying.

[0023] In order to facilitate automatic water filling in the water tank, the water tank is connected to a water supply device, which includes a water storage tank 26, and the water outlet of the water storage tank 26 is connected to the inside of the water tank through a stop valve 27 and a pipeline 29. A liquid level gauge 210 is provided on the vertical extension section 23 of the shelf to ensure that the liquid level height of the water filling is less than the height of the vial material.

[0024] A transparent observation section 28 is provided on the vertical extension section 23 of the shelf, and its position is consistent with the position of the observation window outside the drying box, so as to observe the sublimation of the material.

[0025] The two ends of the baffle 24 are fixed to the opening of the shelf vertical extension section 23 by bolt connection. A fixed position of the baffle 24 is set at the feeding position of the upper shelf 21 for installing the baffle 24 after the vial feeding is completed. The height of the baffle 24 is 1-2 cm, and it is sealed with the upper shelf 21 after installation.

[0026] The pre-freezing method of the freeze-drying structure of the above-mentioned embodiment 2 is adopted. Water is first poured into the water tank at the top of the upper shelf 21, and the liquid level is not higher than the height of the vial material; then the water temperature in the water tank is lowered by the heat transfer oil in the upper shelf 21, thereby forming a uniform cooling environment around the vial, so that the temperature of the material in the vial is lowered. After the water tank temperature reaches the equilibrium freezing temperature, the ultrasonic generator 22 is turned on, and the ultrasonic oscillation is transmitted to the vial through the upper shelf 21 to induce nucleation, so that the material in the vial is evenly frozen. In the sublimation stage, the water in the water tank will be gradually sublimated as the temperature of the upper shelf 21 gradually increases. After the freeze-drying of the material is completed, water will not remain on the upper shelf 21.

[0027] The above describes a specific embodiment of the present invention, but those skilled in the art should understand that this is only an example. Those skilled in the art can make various changes or modifications to this embodiment without departing from the principle and essence of the present invention, but these changes and modifications will fall within the scope of protection of the present invention.

Claims

1. A freeze-drying structure for inducing nucleation by ultrasonic oscillation, comprising a shelf having a heat transfer oil inlet and a heat transfer oil outlet, characterized in that: An ultrasonic generator is arranged on the shelf; a conducting plate is fixed on the top of the shelf, and the ultrasonic generator is located on the top of the conducting plate.

2. A freeze-drying structure for inducing nucleation by ultrasonic oscillation, comprising a shelf having a heat transfer oil inlet and a heat transfer oil outlet, characterized in that: The shelf is provided with an ultrasonic generator; the shelf includes an upper shelf, and the ultrasonic generator is embedded in the bottom of the upper shelf; the top periphery of the upper shelf is provided with a shelf vertical extension section and a baffle, the shelf vertical extension section and the baffle are enclosed at the top of the upper shelf to form a water tank, and the shelf vertical extension section is connected with a heat transfer oil inlet pipe and a heat transfer oil outlet pipe.

3. The freeze-dried structure induced nucleation by ultrasonic oscillation according to claim 2, characterized in that: The shelf also includes a lower shelf connected and fixed below the upper shelf.

4. The freeze-dried structure induced nucleation by ultrasonic oscillation according to claim 3, characterized in that: The upper shelf and the lower shelf are fixed by bolt connection or welding.

5. The freeze-dried structure induced nucleation by ultrasonic oscillation according to claim 2, characterized in that: The water tank is connected to a water supply device, which includes a water storage tank, and the water outlet end of the water storage tank is connected to the inside of the water tank through a stop valve and a pipeline.

6. The freeze-dried structure induced nucleation by ultrasonic oscillation according to claim 2, characterized in that: A liquid level meter is arranged on the vertical extension section of the shelf.

7. The freeze-dried structure induced nucleation by ultrasonic oscillation according to claim 2, characterized in that: A transparent observation section is arranged on the vertical extension section of the shelf.

8. The freeze-dried structure induced nucleation by ultrasonic oscillation according to claim 2, characterized in that: The two ends of the baffle are connected and fixed to the opening of the vertical extension section of the shelf through bolts.

9. A method for prefreezing a freeze-dried structure by inducing nucleation through ultrasonic oscillation according to any one of claims 2 to 8, characterized in that: Start to pour water into the water tank on the top of the upper shelf, the liquid level is not higher than the height of the vial material; then the water temperature in the water tank is lowered by the heat transfer oil in the upper shelf, thereby forming a uniform cooling environment around the vial, so that the temperature of the material in the vial is reduced. After the water tank temperature reaches the equilibrium freezing temperature, turn on the ultrasonic generator to transmit the ultrasonic oscillation to the vial through the upper shelf, inducing nucleation, so that the material in the vial is evenly frozen.

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