Freeze-drying method and freeze-drying system

Abstract

The invention relates to a freeze-drying method and a freeze-drying system, and belongs to the technical field of freeze-drying. The freeze-drying system comprises a freeze-drying container and a stirring device, a jacket is arranged on the outer wall of the freeze-drying container, the stirring device is arranged in the freeze-drying container, and the freeze-drying method comprises the steps that 1, feed liquid is injected into the freeze-drying container, the stirring device is used for stirring the feed liquid at the speed not lower than 60 r / min, a heat exchange medium with the temperature ranging from-3 DEG C to-8 DEG C is introduced into the jacket, and the feed liquid is pre-cooled to-3 DEG C to-5 DEG C; (2) vacuumizing the freeze-drying container, continuously stirring the feed liquid at the speed of not less than 60r / min by using a stirring device, and introducing a heat exchange medium at the temperature of-15 DEG C to-30 DEG C into the jacket, so that the temperature of the feed liquid is reduced to-12 DEG C to-20 DEG C; and (3) continuously stirring until the vacuum degree in the freeze-drying container is reduced to 8-12pa, and then heating and drying. The method can be used for directly freeze-drying to form a powdery product with smaller particle size, and has the advantages of fewer process flows, higher freeze-drying efficiency, less product loss and pollution and low cost.

Description

Technical Field

[0001] The present application relates to the field of freeze-drying technology, and in particular to a freeze-drying method and a freeze-drying system. Background Art

[0002] Freeze-drying technology is used to prepare various medicines, including antibiotics, vaccines, biological products, plasma, etc. Freeze-dried medicines have a longer shelf life and are easier to transport and store. At the same time, many vaccines are prepared through freeze-drying technology to ensure that they will not become ineffective during transportation and storage.

[0003] At present, most freeze-drying equipment used for large-scale production is a tray-type freeze dryer, which is a device that places materials on a tray for freeze drying. The current process of the existing tray-type freeze dryer has the following disadvantages: 1. The materials need to be frozen at a lower temperature to form ice cubes in the early stage of freeze drying, which takes a long time and consumes a lot of energy; 2. The heat exchange efficiency during the freeze drying process decreases as the freeze drying process progresses; 3. The freeze-dried product needs to be processed again to obtain the required powdered product; 4. There are many process flows, and the product is easy to lose and contaminate; 5. When freeze drying materials with low bulk density, disposable freeze drying trays are required, which increases the freeze drying cost. Summary of the invention

[0004] In view of the shortcomings of the prior art, the purpose of the embodiments of the present application is to improve the problems of the current tray-type freeze-drying process, such as long freezing time, low freeze-drying efficiency, high cost, inability to directly obtain the required powdered product, easy product loss and contamination.

[0005] In a first aspect, an embodiment of the present application provides a freeze-drying method, wherein the freeze-drying system comprises a freeze-drying container and a stirring device, wherein the outer wall of the freeze-drying container is provided with a jacket, and the stirring device is provided in the freeze-drying container, and the freeze-drying method comprises:

[0006] (1) injecting the feed liquid into the freeze-drying container, stirring the feed liquid with a stirring device at not less than 60 r / min, and introducing a heat exchange medium at -3°C to -8°C into the jacket to precool the feed liquid to -3°C to -5°C;

[0007] (2) evacuating the freeze-drying container, and continuously stirring the feed liquid with a stirring device at not less than 60 r / min, and introducing a heat exchange medium at -15°C to -30°C into the jacket to cool the feed liquid to -12°C to -20°C;

[0008] (3) Continue stirring until the vacuum degree in the freeze-drying container drops to 8-12 Pa, then heat and dry.

[0009] The present application directly injects the feed liquid into the freeze-drying container, introduces a heat exchange medium at -3°C to -8°C into the jacket, pre-cools the feed liquid to -3°C to -5°C at an appropriate stirring speed, then evacuates the container, introduces a heat exchange medium at -15°C to -30°C into the jacket, and continues to cool the feed liquid to -12°C to -20°C at an appropriate stirring speed. A negative pressure volatilization and endothermic pre-freezing method is adopted, so that most of the water in the feed liquid can be pre-volatilized while freezing, thereby reducing the freezing time and the subsequent drying time. In combination with stirring, the feed liquid is directly freeze-dried through an ice-water mixture, an ice smoothie state, a large-grain ice smoothie, and a small-grain ice smoothie, thereby ensuring that the feed liquid forms smaller ice smoothie particles during the entire freeze-drying process, and can be directly freeze-dried to form a powdered product with a smaller particle size. The process flow is relatively simple, the freeze-drying efficiency is relatively high, the product loss and pollution are relatively small, and the cost is low.

[0010] In some embodiments of the present application, step (3) includes: stirring until the liquid feed forms a fine powder, controlling the stirring rate to 10-20 r / min and stirring until the vacuum degree in the freeze-drying container drops to 8-12 Pa.

[0011] The present application stirs until the material liquid forms a fine powder form, and most of the free water in the material evaporates. At this time, the density of the material is low, and the stirring rate is reduced to avoid the material flying, escaping and losing. The stirring is continued to evaporate the free water in the material as much as possible, until the vacuum degree in the freeze-drying container drops to 8-12 Pa, and the free water in the material is almost completely evaporated.

[0012] In some embodiments of the present application, heating and drying include: heating to -8°C ~ -10°C and maintaining for 4-8 hours; each time the vacuum degree in the freeze-drying container drops to 8-12 Pa, the temperature is raised by 8°C -12°C and maintained for 4-8 hours, until the temperature rises to 25-35°C and maintained for 4-8 hours.

[0013] After the free water in the material is almost completely volatilized, the present application continues to dry the material by increasing the temperature in stages, so as to continue to efficiently volatilize and remove the bound water in the material, while avoiding damage to the quality of the product.

[0014] In some embodiments of the present application, the freeze-drying system also includes a temperature control device, which is located in the circulation loop of the heat exchange medium. The freeze-drying method also includes: after the feed liquid is pre-cooled to -3°C to -5°C, a portion of the heat exchange medium at -3°C to -8°C is located in the jacket to pre-cool the feed liquid. At this time, another portion of the heat exchange medium at -3°C to -8°C is circulated and continuously cooled to -15°C to -30°C under the control of the temperature control device, and the heat exchange medium that has been circulated and cooled to -15°C to -30°C by the control device is introduced into the jacket.

[0015] The present application has the following steps: after the feed liquid is precooled to -3°C to -5°C, a portion of the heat exchange medium at -3°C to -8°C is continuously cooled to -15°C to -30°C under the control of a temperature control device, and the heat exchange medium cooled to -15°C to -30°C by the control device is introduced into the jacket, so that the feed liquid precooled to -3°C to -5°C is quickly cooled to -12°C to -20°C, so that the raw material solution and water in the feed liquid reach the same eutectic point, thereby facilitating subsequent efficient volatilization freeze-drying.

[0016] In a second aspect, an embodiment of the present application provides a freeze-drying system, which is applicable to the freeze-drying method provided in the first aspect, including: a freeze-drying container, a temperature control device and a stirring device, the outer wall of the freeze-drying container is provided with a jacket, and a heat exchange medium is injected into the jacket; the temperature control device includes a heat exchange device and a box body, one end of the heat exchange device is connected to the inlet of the jacket through a first pipeline, and the other end of the heat exchange device is connected to the outlet of the jacket through a second pipeline, and a pump body is provided on the first pipeline; the box body is arranged in the first pipeline and is connected to the inlet of the jacket and the heat exchange device; the second pipeline is connected to the first pipeline between the box body and the inlet of the jacket, and a third pipeline is connected, a first valve body is provided on the first pipeline and the first valve body is located between the connection between the third pipeline and the first pipeline and the inlet of the jacket, a second valve body is provided on the second pipeline and the second valve body is located between the connection between the third pipeline and the second pipeline and the outlet of the jacket, and a circulation valve body is provided on the third pipeline; the stirring device is arranged in the freeze-drying container, for stirring the liquid injected into the freeze-drying container.

[0017] The present application connects one end of the heat exchange device to the inlet of the jacket through a first pipeline, and the other end of the heat exchange device to the outlet of the jacket through a second pipeline. A pump body is arranged on the first pipeline, so that the heat exchange medium in the jacket can be cooled, thereby precooling the liquid in the freeze-drying container to -3°C to -5°C; by arranging a box body on the first pipeline and connecting the inlet of the jacket and the heat exchange device, connecting the second pipeline to the first pipeline between the box body and the inlet of the jacket, and connecting the third pipeline, a first valve body is arranged on the first pipeline and the first valve body is located between the connection between the third pipeline and the first pipeline and the inlet of the jacket, a second valve body is arranged on the second pipeline and the second valve body is connected to the inlet of the jacket. The valve body is located between the connection between the third pipeline and the second pipeline and the outlet of the jacket. A circulation valve body is arranged on the third pipeline to circulate and cool the heat exchange medium in the jacket to a required lower temperature, thereby realizing rapid cooling of the feed liquid precooled to -3°C to -5°C in the freeze-drying container to -12°C to -20°C; and the stirring device is used to make the feed liquid directly undergo ice-water mixture, ice smoothie state, large-grain ice smoothie, and small-grain ice smoothie for freeze-drying, ensuring that the feed liquid forms smaller ice smoothie particles during the entire freeze-drying process, and can be directly freeze-dried to form a powdered product with a smaller particle size; there are fewer process flows, higher freeze-drying efficiency, less product loss and pollution, and low cost.

[0018] In some embodiments of the present application, the stirring device includes a driving member and a stirring member, the driving member is used to drive the stirring member to rotate, the stirring member extends from the top of the freeze-drying container into the freeze-drying container and extends to the bottom of the freeze-drying container; the stirring member includes a stirring shaft and a plurality of stirring blades, and the plurality of stirring blades are distributed at intervals along the axial and circumferential directions of the stirring shaft.

[0019] The present application arranges a stirring member to extend into the freeze-drying container from the top of the freeze-drying container, that is, the freeze-drying container is vertical and suitable for freeze-drying the liquid feed; and by arranging a plurality of stirring blades at intervals in the axial and circumferential directions of the stirring shaft, it is convenient to fully stir and freeze-dry the liquid feed in the freeze-drying container.

[0020] In some embodiments of the present application, the distance between the edge of the stirring blade close to the inner wall of the freeze-drying container and the inner wall of the freeze-drying container is less than 3 mm.

[0021] The present application arranges the distance between the edge of the stirring blade close to the inner wall of the freeze-drying container and the inner wall of the freeze-drying container to be less than 3 mm to ensure that the material in the freeze-drying container can be fully stirred. When the material is frozen to form a smoothie or a granular smoothie, some smoothies and granular smoothies may adhere to the inner wall of the freeze-drying container. The above-mentioned arrangement of the stirring blade can also fully stir the smoothie and granular smoothie materials attached to the inner wall of the freeze-drying container to ensure that the material forms smaller smoothie particles during the entire freeze-drying process and is freeze-dried sufficiently and evenly.

[0022] In some embodiments of the present application, the polishing cleanliness of the inner wall of the freeze-drying container and the outer wall of the stirring element are both less than 4 μm.

[0023] The present application uses a freeze-drying container with an inner wall and a stirring element with a polishing cleanliness of less than 4 μm, which is conducive to efficient stirring and freeze-drying of the liquid.

[0024] In some embodiments of the present application, the freeze-drying container is connected to a vacuum pump.

[0025] The present application connects the freeze-drying container to a vacuum pump so as to evacuate the freeze-drying container during the freeze-drying process, so as to efficiently perform negative pressure volatilization and heat absorption pre-freezing and drying on the liquid in the freeze-drying container.

[0026] In some embodiments of the present application, the freeze-drying container is connected to a nitrogen storage tank.

[0027] The present application connects the freeze-drying container to a nitrogen storage tank to verify the airtightness of the freeze-drying container and ensure good operation during vacuuming; at the same time, after the freeze-drying container is discharged, if there is material remaining in the freeze-drying container, the freeze-drying container can be purged with nitrogen. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] In order to more clearly illustrate the technical solutions of the embodiments of the present application, the drawings required for use in the embodiments will be briefly introduced below. It should be understood that the following drawings only show certain embodiments of the present application and therefore should not be regarded as limiting the scope. For ordinary technicians in this field, other related drawings can be obtained based on these drawings without paying creative work.

[0029] Figure 1 A schematic diagram of a freeze-drying system provided in an embodiment of the present application.

[0030] Icons: 1-freeze drying container; 11-jacket; 12-feed port; 13-discharge port; 14-first pressure gauge; 15-first thermometer; 2-temperature control device; 21-heat exchange device; 22-box; 23-first pipeline; 231-first valve body; 24-second pipeline; 241-second valve body; 25-pump body; 26-third pipeline; 261-circulation valve body; 27-third thermometer; 3-stirring device; 31-driving member; 32-stirring shaft; 33-stirring blade; 4-vacuum pump; 41-second pressure gauge; 42-second thermometer; 43-vacuum regulating valve; 5-nitrogen storage tank; 51-nitrogen regulating valve. DETAILED DESCRIPTION

[0031] In order to make the purpose, technical scheme and advantages of the embodiments of the present application clearer, the technical scheme in the embodiments of the present application will be described clearly and completely below. If the specific conditions are not specified in the embodiments, they are carried out according to the conventional conditions or the conditions recommended by the manufacturer. If the manufacturer is not specified for the reagents or instruments used, they are all conventional products that can be purchased commercially.

[0032] In order to improve the current tray-type freeze-drying process, the problems of long freezing time, low freeze-drying efficiency, high cost, inability to directly obtain the required powdered product, easy product loss and contamination, etc.

[0033] The embodiment of the present application provides a freeze-drying method, wherein the freeze-drying system includes a freeze-drying container and a stirring device, wherein the outer wall of the freeze-drying container is provided with a jacket, and the stirring device is provided in the freeze-drying container, and the freeze-drying method includes:

[0034] (1) injecting the feed liquid into the freeze-drying container, stirring the feed liquid with a stirring device at not less than 60 r / min, and introducing a heat exchange medium at -3°C to -8°C into the jacket to precool the feed liquid to -3°C to -5°C;

[0035] (2) evacuating the freeze-drying container, and continuously stirring the feed liquid with a stirring device at not less than 60 r / min, and introducing a heat exchange medium at -15°C to -30°C into the jacket to cool the feed liquid to -12°C to -20°C;

[0036] (3) Continue stirring until the vacuum degree in the freeze-drying container drops to 8-12 Pa, then heat and dry.

[0037] The feed liquid is directly injected into the freeze-drying container, and a heat exchange medium at -3°C to -8°C is introduced into the jacket. The feed liquid is pre-cooled to -3°C to -5°C at an appropriate stirring speed, so that part of the water in the feed liquid is volatilized first to form a certain ice-water mixture, and it is avoided that a large amount of water is evaporated at one time to form a larger block by direct vacuuming; vacuuming is then performed again, and a heat exchange medium at -15°C to -30°C is introduced into the jacket, and the feed liquid is further cooled to -12°C to -20°C at an appropriate stirring speed. A negative pressure volatilization endothermic pre-freezing method is adopted, so that most of the water in the feed liquid can be pre-volatized while freezing, thereby reducing the freezing time and the subsequent drying time, and the feed liquid is directly freeze-dried through the ice-water mixture, ice smoothie state, large-grain ice smoothie, and small-grain ice smoothie with stirring, so as to ensure that the feed liquid forms smaller ice smoothie particles during the entire freeze-drying process, and can be directly freeze-dried to form a powdered product with a smaller particle size; there are fewer process flows, higher freeze-drying efficiency, less product loss and pollution, and low cost.

[0038] In some embodiments of the present application, the particle size of the powdered product formed by freeze-drying is less than 10 μm.

[0039] In some embodiments of the present application, the volume of the feed solution injected into the freeze-drying container is less than 1 / 2 of the volume of the freeze-drying container.

[0040] Further, the stirring speed is 60-300r / min. As an example, the stirring speed can be, but is not limited to, 60r / min, 65r / min, 70r / min, 75r / min, 80r / min, 85r / min, 90r / min, 95r / min, 100r / min, 150r / min, 200r / min, 300r / min.

[0041] In some embodiments of the present application, step (3) includes: stirring until the liquid material forms a fine powder, controlling the stirring rate to 10-20 r / min and stirring until the vacuum degree in the freeze-drying container drops to 8-12 Pa. When the liquid material is stirred to form a fine powder, most of the free water in the material evaporates. At this time, the density of the material is low. The stirring rate is reduced to avoid the material from flying and escaping. Continue stirring to evaporate the free water in the material as much as possible until the vacuum degree in the freeze-drying container drops to 8-12 Pa, and the free water in the material evaporates almost completely. As an example, the stirring rate can be controlled to be, but not limited to, 10 r / min, 12 r / min, 15 r / min, 18 r / min, and 20 r / min.

[0042] In some embodiments of the present application, the temperature-raising drying includes: raising the temperature to -8°C to -10°C and maintaining it for 4-8 hours; each time the vacuum degree in the freeze-drying container drops to 8-12 Pa, the temperature is raised by 8°C to 12°C and maintained for 4-8 hours, until the temperature rises to 25-35°C and maintained for 4-8 hours. After the free water in the material is almost completely volatilized, the material is dried by continuing to increase the temperature in stages to continue to efficiently volatilize and remove the bound water in the material, while avoiding damage to the quality of the product.

[0043] In some embodiments of the present application, the freeze-drying system also includes a temperature control device, which is located in the circulation loop of the heat exchange medium. The freeze-drying method also includes: after the feed liquid is pre-cooled to -3°C to -5°C, a portion of the heat exchange medium at -3°C to -8°C is located in the jacket to pre-cool the feed liquid. At this time, another portion of the heat exchange medium at -3°C to -8°C is circulated and continuously cooled to -15°C to -30°C under the control of the temperature control device, and the heat exchange medium that has been circulated and cooled to -15°C to -30°C by the control device is introduced into the jacket. After the feed liquid is precooled to -3°C to -5°C, a portion of the heat exchange medium at -3°C to -8°C is continuously cooled to -15°C to -30°C under the control of the temperature control device, and the heat exchange medium cooled to -15°C to -30°C by the control device is introduced into the jacket, so that the feed liquid precooled to -3°C to -5°C is quickly cooled to -12°C to -20°C, so that the raw material solution and water in the feed liquid reach the same eutectic point, thereby facilitating subsequent efficient volatilization and lyophilization, avoiding premature crystallization of water in the feed liquid, concentrating the raw material solution in the feed liquid and changing the lyophilization curve, resulting in inability to lyophilize or poor lyophilization effect.

[0044] In some embodiments of the present application, the above freeze-drying method is applicable to various medicines, including but not limited to antibiotics, vaccines, biological products, and plasma. It is particularly suitable for materials with low bulk density. When materials with low bulk density are freeze-dried on traditional trays, they are loose, easy to fly, and difficult to can. Therefore, disposable freeze-drying trays are required, which are costly. Using the above freeze-drying method to freeze-dry materials with low bulk density can reduce flying losses, make canning easier, and have lower costs.

[0045] The present application embodiment provides a freeze-drying system, such as Figure 1As shown, it is suitable for the above-mentioned freeze-drying method, comprising: a freeze-drying container 1, a temperature control device 2 and a stirring device 3, the outer wall of the freeze-drying container 1 is provided with a jacket 11, and the jacket 11 is filled with a heat exchange medium; the temperature control device 2 comprises a heat exchange device 21 and a box 22, one end of the heat exchange device 21 is connected to the inlet of the jacket 11 through a first pipeline 23, and the other end of the heat exchange device 21 is connected to the outlet of the jacket 11 through a second pipeline 24, and a pump body 25 is provided on the first pipeline 23; the box 22 is arranged on the first pipeline 23 and is connected to the inlet of the jacket 11 and the heat exchange device 21; the second pipeline 24 A third pipeline 26 is connected to the first pipeline 23 between the box body 22 and the inlet of the jacket 11, a first valve body 231 is provided on the first pipeline 23 and the first valve body 231 is located between the connection between the third pipeline 26 and the first pipeline 23 and the inlet of the jacket 11, a second valve body 241 is provided on the second pipeline 24 and the second valve body 241 is located between the connection between the third pipeline 26 and the second pipeline 24 and the outlet of the jacket 11, and a circulation valve body 261 is provided on the third pipeline 26; a stirring device 3 is arranged in the freeze-drying container 1, and is used to stir the liquid injected into the freeze-drying container 1.

[0046] As an example, a third thermometer 27 is provided on the first pipeline 23 between the heat exchange device 21 and the box 22 to detect the temperature of the heat exchange medium after heat exchange through the heat exchange device 21 .

[0047] As an example, the freeze drying container 1 is provided with a first pressure gauge 14 and a first thermometer 15 to detect the pressure in the freeze drying container 1 and the temperature of the material in the freeze drying container 1 .

[0048] The heat exchange device 21 is opened in advance and set to -3°C to -8°C, the first valve body 231, the second valve body 241, the pump body 25 and the heat exchange device 21 are opened, and the pump body 25 draws the heat exchange medium in the jacket 11 from the outlet of the jacket 11 and draws it into the second pipeline 24, so that the heat exchange medium circulates to the heat exchange device 21 to cool down, and the cooled heat exchange medium enters the jacket 11 through the first pipeline 23 and the inlet of the jacket 11, so that the circulated and cooled heat exchange medium is input into the jacket 11 until the heat exchange medium cooled to -3°C to -8°C enters the jacket 11, thereby precooling the feed liquid in the freeze-drying container 1 to -3°C to -5°C; when the feed liquid in the freeze-drying container 1 is cooled to -3°C to -5°C, the heat exchange device 21 is set to -15°C to -30°C in advance, and the first valve body 231, The second valve body 241 is opened, and the circulation valve body 261 is opened. A part of the heat exchange medium at -3℃~-8℃ remains in the jacket 11 to continue precooling the liquid in the freeze-drying container 1, and the other part of the heat exchange medium at -3℃~-8℃ remains in the temperature control device 2, and circulates and cools down between the second pipeline 24, the heat exchange device 21, the first pipeline 23 and the third pipeline 26 until the third thermometer 27 detects that the heat exchange medium has dropped to -15℃~-30℃, then the first valve body 231 and the second valve body 241 are opened, and the circulation valve body 261 is closed, so that the heat exchange medium dropped to -15℃~-30℃ enters the jacket 11 from the inlet of the jacket 11 through the first pipeline 23, thereby cooling the liquid in the freeze-drying container 1 to -12℃~-20℃; wherein, the flow rate of the heat exchange medium is controlled to 8-12m 3 / h.

[0049] In some embodiments of the present application, the stirring device 3 includes a driving member 31 and a stirring member, the driving member 31 is used to drive the stirring member to rotate, the stirring member extends from the top of the freeze-drying container 1 into the freeze-drying container 1, and extends to the bottom of the freeze-drying container 1; the stirring member includes a stirring shaft 32 and a plurality of stirring blades 33, and the plurality of stirring blades 33 are distributed at intervals along the axial direction and circumferential direction of the stirring shaft 32. The stirring member is arranged to extend from the top of the freeze-drying container 1 into the freeze-drying container 1, that is, the freeze-drying container 1 is vertical, suitable for freeze-drying the feed liquid; by distributing a plurality of stirring blades 33 at intervals along the axial direction and circumferential direction of the stirring shaft 32, it is convenient to fully stir and freeze-dry the feed liquid in the freeze-drying container 1.

[0050] As an example, the stirring element may be, but not limited to, an anchor stirring element or a ribbon stirring element. The driving element 31 may be, but not limited to, a variable frequency motor.

[0051] In some embodiments of the present application, the distance between the edge of the stirring blade 33 close to the inner wall of the freeze-drying container 1 and the inner wall of the freeze-drying container 1 is less than 3 mm. The distance between the edge of the stirring blade 33 close to the inner wall of the freeze-drying container 1 and the inner wall of the freeze-drying container 1 is set to be less than 3 mm to ensure that the material in the freeze-drying container 1 can be fully stirred. When the material is frozen to form a smoothie and a granular smoothie state, some smoothies and granular smoothies may adhere to the inner wall of the freeze-drying container 1. The above-mentioned setting of the stirring blade 33 can also fully stir the smoothie and granular smoothie state materials attached to the inner wall of the freeze-drying container 1 to ensure that the material forms smaller smoothie particles during the entire freeze-drying process and is fully and evenly freeze-dried.

[0052] Further, the distance between the edge of the stirring blade 33 close to the inner wall of the freeze-drying container 1 and the inner wall of the freeze-drying container 1 is 0.5-2.8 mm. As an example, the distance between the edge of the stirring blade 33 close to the inner wall of the freeze-drying container 1 and the inner wall of the freeze-drying container 1 can be, but is not limited to, 2.8 mm, 2.5 mm, 2.2 mm, 2 mm, 1.8 mm, 1.5 mm, 1.2 mm, 1 mm, 0.8 mm, 0.5 mm.

[0053] In some embodiments of the present application, the polishing cleanliness of the inner wall of the freeze-drying container 1 and the outer wall of the stirring element is less than 4 μm. The polishing cleanliness of the inner wall of the freeze-drying container 1 and the outer wall of the stirring element is less than 4 μm, which is conducive to efficient stirring and freeze-drying of the liquid.

[0054] Further, the polishing cleanliness of the inner wall of the freeze-drying container 1 and the outer wall of the stirring member is 0.1-3.5 μm. As an example, the polishing cleanliness of the inner wall of the freeze-drying container 1 and the outer wall of the stirring member can be, but is not limited to, 3.5 μm, 3 μm, 2.5 μm, 2 μm, 1.5 μm, 1 μm, 0.5 μm, 0.3 μm, 0.2 μm, and 0.1 μm.

[0055] In some embodiments of the present application, a feed port 12 is provided at the top of the freeze-drying container 1, and a discharge port 13 is provided at the bottom of the freeze-drying container 1. The feed port 12 is provided at the top of the freeze-drying container 1, and the discharge port 13 is provided at the bottom. The feed liquid enters the freeze-drying container 1 from the feed port 12, and the freeze-dried product formed after the freeze-drying is completed is directly discharged from the discharge port 13, which is conducive to the processing of the feed liquid.

[0056] As an example, the discharge port 13 is provided with a discharge valve. So that after the freeze-drying is completed, the discharge valve can be opened to discharge the freeze-dried product. The discharge port 13 can be directly connected to a subsequent process device, so that the freeze-dried product can be directly transported to the subsequent process device for processing, so as to reduce the loss and contamination of the freeze-dried product.

[0057] In some embodiments of the present application, the freeze-drying container 1 is connected to a vacuum pump 4. The freeze-drying container 1 is connected to the vacuum pump 4 so as to evacuate the freeze-drying container 1 during the freeze-drying process, so as to efficiently perform negative pressure volatilization and heat absorption pre-freezing and drying on the liquid in the freeze-drying container 1. As an example, the vacuum pump 4 can be, but is not limited to, a Roots screw vacuum pump 4.

[0058] As an example, the connecting pipeline between the freeze drying container 1 and the vacuum pump 4 is provided with a second thermometer 42, a vacuum regulating valve 43 and a second pressure gauge 41 in sequence. In order to facilitate the connection or disconnection between the freeze drying container 1 and the vacuum pump 4 through the vacuum regulating valve 43, the second thermometer 42 detects the temperature in real time, and the second pressure gauge 41 detects the pressure in real time.

[0059] After the vacuum pump 4 is turned on, when the second pressure gauge 41 detects that the pressure is lower than 2 Pa, the test indicates that the vacuum pump 4 is operating well and can continue to work. At the same time, after the vacuum pump 4 is turned on, the vacuum regulating valve 43 is opened. When the first pressure gauge 14 detects that the pressure in the freeze-drying container 1 reaches 0 Pa ± 0.02 Pa, the test indicates that the freeze-drying container 1 is airtight, the vacuum pump 4 is operating well, and the freeze-drying container 1 and the vacuum pump 4 are working well together and can continue to work.

[0060] In some embodiments of the present application, the freeze-drying container 1 is connected to a nitrogen storage tank 5. The freeze-drying container 1 is connected to the nitrogen storage tank 5 to verify the airtightness of the freeze-drying container 1 and ensure good operation during vacuuming; at the same time, after the freeze-drying container 1 is discharged, if there is material remaining in the freeze-drying container 1, the freeze-drying container 1 can be purged with nitrogen.

[0061] As an example, a nitrogen regulating valve 51 is provided on the connecting pipeline between the freeze drying container 1 and the nitrogen storage tank 5 to control the delivery and closing of nitrogen. The nitrogen regulating valve 51 is opened, and the nitrogen is delivered into the freeze drying container 1. When the first pressure gauge 14 detects that the pressure in the freeze drying container 1 reaches 0.08Mpa, the nitrogen regulating valve 51 is closed, and the container is left to stand for 15 minutes. After 15 minutes, the pressure detected by the first pressure gauge 14 is not lower than 0.078Mpa, and the test shows that the airtightness of the freeze drying container 1 is good.

[0062] In some embodiments of the present application, the first pressure gauge 14, the first thermometer 15, the heat exchange device 21, the first valve body 231, the second valve body 241, the pump body 25, the circulation valve body 261, the third thermometer 27, the drive 31, the vacuum pump 4, the second pressure gauge 41, the second thermometer 42, and the vacuum regulating valve 43 are electrically connected to the electrical control system respectively. The electrical control system includes a host computer and a slave computer. As an example, the host computer is an industrial computer or an industrial human-machine interface. The slave computer is a PLC.

[0063] The features and performance of the present application are further described in detail below in conjunction with the embodiments.

[0064] Example 1

[0065] This embodiment provides a freeze-drying method, wherein the freeze-drying system includes a freeze-drying container, a stirring device and a temperature control device, wherein the outer wall of the freeze-drying container is provided with a jacket, the stirring device is provided in the freeze-drying container, and the temperature control device is located in a circulation loop of a heat exchange medium. The freeze-drying method includes:

[0066] (1) 5 L of 10% raffinose aqueous solution was injected into the freeze-drying container through the feed port, the feed liquid was stirred at 60 r / min using a stirring device, and a -5°C heat exchange medium was introduced into the jacket to precool the feed liquid to -3°C; after the feed liquid was precooled to -3°C, a portion of the -3°C heat exchange medium was located in the jacket to precool the feed liquid, and at this time, another portion of the -3°C heat exchange medium was circulated and continuously cooled to -20°C under the control of the temperature control device;

[0067] (2) Evacuate the freeze-drying container, continue to use a stirring device to stir the feed liquid at 60 r / min, and introduce a -20°C heat exchange medium into the jacket to cool the feed liquid to -15°C;

[0068] (3) Stir until the liquid forms a fine powder, control the stirring rate to 20 r / min and stir until the vacuum degree in the freeze-drying container drops to 10 Pa; then raise the temperature to -10°C and maintain for 6 hours; each time the vacuum degree in the freeze-drying container drops to 10 Pa, raise the temperature by 10°C and maintain for 6 hours, until the temperature rises to 30°C and maintain for 6 hours.

[0069] The freeze-drying method of this embodiment takes 34 hours to complete the entire freeze-drying process.

[0070] Comparative Example 1

[0071] The comparative example provides a freeze-drying method, wherein a 10% mass concentration of cottonseed sugar aqueous solution is added to a disposable freeze-drying plate, the filling height is 10 mm, and then the freeze-drying plate is placed in a tray freeze-drying device, and then the freeze-drying program is started, the temperature of the layer plate is first cooled to -36°C and maintained for 5 hours, the product is pre-frozen, and the cold trap is pre-cooled to -70°C, and then the vacuum pump is turned on, and when the vacuum degree reaches below 15 Pa, the layer plate is started to be heated to -25°C, the temperature recovery rate is controlled at 5°C / h, and then maintained in this state for 72 hours, until the curves of the Pirani vacuum gauge and the capacitance film silicon vacuum gauge in the freeze-drying cavity coincide, the layer plate is heated for a second time, the temperature is raised to 30°C, the temperature recovery rate is controlled at 5°C / h, and then maintained in this state for 72 hours, and then the equipment is vented with nitrogen to restore the cavity to normal pressure, the disposable freeze-drying plate is taken out in the isolator, the film is torn off, the block product is removed with a spatula, put into a mixer, crushed by shaking, and finally taken out to enter the packaging process.

[0072] The freeze-drying method of this comparative example takes 144 hours to complete the entire freeze-drying process.

[0073] The embodiments described above are part of the embodiments of the present application, rather than all of the embodiments. The detailed description of the embodiments of the present application is not intended to limit the scope of the present application for protection, but merely represents the selected embodiments of the present application. Based on the embodiments in the present application, all other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of the present application.

Claims

1. A freeze-drying method, characterized in that: The freeze-drying system comprises a freeze-drying container and a stirring device, wherein the outer wall of the freeze-drying container is provided with a jacket, and the stirring device is arranged inside the freeze-drying container. The freeze-drying method comprises: (1) injecting the feed liquid into the freeze-drying container, stirring the feed liquid with the stirring device at a speed of not less than 60 r / min, and introducing a heat exchange medium at -3°C to -8°C into the jacket to precool the feed liquid to -3°C to -5°C; (2) evacuating the freeze-drying container, and continuously stirring the feed liquid using the stirring device at a speed of not less than 60 r / min, and introducing a heat exchange medium at -15°C to -30°C into the jacket to cool the feed liquid to -12°C to -20°C; (3) Continue stirring until the vacuum degree in the freeze-drying container drops to 8-12 Pa, then heat and dry.

2. The freeze-drying method according to claim 1, characterized in that The step (3) comprises: stirring until the liquid material is in a fine powder form, controlling the stirring rate to 10-20 r / min and stirring until the vacuum degree in the freeze-drying container drops to 8-12 Pa.

3. The freeze-drying method according to claim 1, characterized in that The temperature-raising drying includes: raising the temperature to -8°C to -10°C and maintaining it for 4-8 hours; each time the vacuum degree in the freeze-drying container drops to 8-12 Pa, raising the temperature by 8°C to 12°C and maintaining it for 4-8 hours, until the temperature rises to 25-35°C and maintaining it for 4-8 hours.

4. The freeze-drying method according to claim 1, characterized in that The freeze-drying system further includes a temperature control device, which is located in the circulation loop of the heat exchange medium. The freeze-drying method further includes: When the feed liquid is precooled to -3℃~-5℃, a part of the heat exchange medium at -3℃~-8℃ is located in the jacket to precool the feed liquid. At this time, another part of the heat exchange medium at -3℃~-8℃ is circulated and continuously cooled to -15℃~-30℃ under the control of the temperature control device, and the heat exchange medium circulated and cooled to -15℃~-30℃ by the control device is introduced into the jacket.

5. A freeze-drying system, characterized in that: The freeze-drying method according to any one of claims 1 to 4, comprising: A freeze-drying container, wherein the outer wall of the freeze-drying container is provided with a jacket, and a heat exchange medium is injected into the jacket; A temperature control device, the temperature control device comprises a heat exchange device and a casing, one end of the heat exchange device is connected to the inlet of the jacket through a first pipeline, the other end of the heat exchange device is connected to the outlet of the jacket through a second pipeline, a pump body is arranged on the first pipeline; the casing is arranged on the first pipeline and is connected to the inlet of the jacket and the heat exchange device; the second pipeline is connected to the first pipeline between the casing and the inlet of the jacket and is connected to a third pipeline, a first valve body is arranged on the first pipeline and the first valve body is located between the connection between the third pipeline and the first pipeline and the inlet of the jacket, a second valve body is arranged on the second pipeline and the second valve body is located between the connection between the third pipeline and the second pipeline and the outlet of the jacket, and a circulation valve body is arranged on the third pipeline; A stirring device is arranged in the freeze-drying container and is used to stir the feed liquid injected into the freeze-drying container.

6. The freeze-drying system according to claim 5, characterized in that: The stirring device includes a driving member and a stirring member, wherein the driving member is used to drive the stirring member to rotate, and the stirring member extends from the top of the freeze-drying container into the freeze-drying container and extends toward the bottom of the freeze-drying container; the stirring member includes a stirring shaft and a plurality of stirring blades, and the plurality of stirring blades are distributed at intervals along the axial and circumferential directions of the stirring shaft.

7. The freeze-drying system according to claim 6, characterized in that: The distance between the edge of the stirring blade close to the inner wall of the freeze-drying container and the inner wall of the freeze-drying container is less than 3 mm.

8. The freeze-drying system according to claim 6, characterized in that: The polishing cleanliness of the inner wall of the freeze-drying container and the outer wall of the stirring element is less than 4 μm.

9. The freeze-drying system according to any one of claims 5 to 8, characterized in that: The freeze-drying container is communicated with a vacuum pump.

10. The freeze-drying system according to any one of claims 5 to 8, characterized in that: The freeze-drying container is communicated with a nitrogen storage tank.

Images