WO2011120342A1 - Vacuum freeze-drying apparatus - Google Patents

Vacuum freeze-drying apparatus Download PDF

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Publication number
WO2011120342A1
WO2011120342A1 PCT/CN2011/070189 CN2011070189W WO2011120342A1 WO 2011120342 A1 WO2011120342 A1 WO 2011120342A1 CN 2011070189 W CN2011070189 W CN 2011070189W WO 2011120342 A1 WO2011120342 A1 WO 2011120342A1
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Prior art keywords
freeze
vacuum
drying chamber
drying
dsc
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PCT/CN2011/070189
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French (fr)
Chinese (zh)
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王海燕
吕树申
伦照荣
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中山大学
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Publication of WO2011120342A1 publication Critical patent/WO2011120342A1/en

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    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F26—DRYING
    • F26B—DRYING SOLID MATERIALS OR OBJECTS BY REMOVING LIQUID THEREFROM
    • F26B5/00—Drying solid materials or objects by processes not involving the application of heat
    • F26B5/04—Drying solid materials or objects by processes not involving the application of heat by evaporation or sublimation of moisture under reduced pressure, e.g. in a vacuum
    • F26B5/06—Drying solid materials or objects by processes not involving the application of heat by evaporation or sublimation of moisture under reduced pressure, e.g. in a vacuum the process involving freezing
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N25/00—Investigating or analyzing materials by the use of thermal means
    • G01N25/20—Investigating or analyzing materials by the use of thermal means by investigating the development of heat, i.e. calorimetry, e.g. by measuring specific heat, by measuring thermal conductivity
    • G01N25/48—Investigating or analyzing materials by the use of thermal means by investigating the development of heat, i.e. calorimetry, e.g. by measuring specific heat, by measuring thermal conductivity on solution, sorption, or a chemical reaction not involving combustion or catalytic oxidation
    • G01N25/4846—Investigating or analyzing materials by the use of thermal means by investigating the development of heat, i.e. calorimetry, e.g. by measuring specific heat, by measuring thermal conductivity on solution, sorption, or a chemical reaction not involving combustion or catalytic oxidation for a motionless, e.g. solid sample
    • G01N25/4866—Investigating or analyzing materials by the use of thermal means by investigating the development of heat, i.e. calorimetry, e.g. by measuring specific heat, by measuring thermal conductivity on solution, sorption, or a chemical reaction not involving combustion or catalytic oxidation for a motionless, e.g. solid sample by using a differential method
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/01—Arrangements or apparatus for facilitating the optical investigation
    • G01N21/03—Cuvette constructions
    • G01N21/0332—Cuvette constructions with temperature control
    • G01N2021/0335—Refrigeration of cells; Cold stages

Definitions

  • the present invention relates to a vacuum freeze-drying apparatus, and more particularly to a vacuum freeze-drying apparatus having a DSC and a microstructure observation function.
  • Vacuum freeze-drying is a drying method in which a material containing water is frozen at a low temperature to form ice, and then the frozen material is heated under vacuum to sublimate the ice to obtain a dry product.
  • vacuum freeze-drying technology is undoubtedly the most ideal production and processing method in order to prevent denaturation due to excessive temperature during production. Freeze-dried biological products and pharmaceuticals are generally prepared as injections, and for the convenience of storage and use, the lyophilized form of the bottled materials is usually used.
  • the lyophilizer is a device commonly used in vacuum freeze-drying. Because of the small contact area between the heating separator and the bottled material, heat transfer tends to be the main control step of the freeze-drying process, and the sublimation interface uniformly moves to the bottom of the bottle. The heat transfer model became the main guiding model for experimentation and production. The one-dimensional heat transfer model ignores the heat transfer from the side of the bottle. However, in practice, the thickness of the bottled material can be compared with the bottleneck size, and the effect of radial heat transfer on the freeze-drying process is not negligible. In addition, the influencing factors of the freeze-drying process are more and related, so the experimental parameters can be used to obtain suitable freeze-drying parameters and processes.
  • a successful lyophilization process depends not only on the structural knowledge of the lyophilized product, but also on the heat and kinetics of the lyophilization.
  • the most commonly used method of structural research and thermal analysis is differential scanning calorimetry (DSC).
  • DSC differential scanning calorimetry
  • the method can measure the difference in temperature change process between the sample and the sensor probe, and its thermal behavior is recorded, according to the recorded DSC Curves allow analysis of the freezing point, freezing characteristics, and glass transition characteristics of lyophilized samples.
  • the microscope is one of the most intuitive structural research methods, which can directly observe the microstructure of the sample to be tested.
  • a DSC In order to fully and thoroughly study the freeze-drying of heat-sensitive substances such as bottled biological products and pharmaceuticals and obtain practical data to provide more effective reference and guidance for their actual production, a DSC is required. And a vacuum freeze drying device with a microstructure observation function.
  • a vacuum freeze-drying device with DSC and microstructure observation function which is a freeze-drying system, a vacuum system, a DSC thermal analysis system, a micro camera system, a residual moisture measuring system and a computer;
  • the freeze drying system comprises a freeze drying chamber, a heating device and a refrigeration device, the freeze drying chamber is a closed container, the container wall is provided with a transparent portion, a heating device and a cooling device Located in the freeze drying chamber; the freeze drying chamber is connected to the vacuum system;
  • the DSC thermal analysis system is located inside the freeze drying chamber;
  • the microscopic camera system is arranged outside the freeze-drying chamber, and the internal sample microstructure can be observed through the transparent portion on the wall of the freeze-drying chamber;
  • the residual moisture measuring system is arranged inside the freeze-drying chamber, and the water vapor partial pressure in the freeze-drying chamber is measured to measure The residual moisture content of the lyophilized material;
  • the DSC thermal analysis system, microscopic camera system, and residual moisture measurement system
  • the refrigeration device comprises a heat transfer rod and liquid nitrogen, the bottom of the freeze-drying chamber is connected to one end of the heat transfer rod, and the other end of the heat transfer rod is immersed in liquid nitrogen. Thereby, the cold amount is transferred to the drying chamber, and thereby the sample in the drying chamber is cooled and frozen.
  • the liquid nitrogen is provided on a lifting platform.
  • the depth at which the heat transfer rod is immersed in liquid nitrogen can be freely adjusted by the lifting table.
  • the heating device comprises an electric heating wire and a thermostat.
  • the electric heating wire is evenly installed on the outer surface of the drying chamber container, and the heating power is adjusted according to the set temperature program by the thermostat to provide a heat source for the sample in the freeze-drying chamber.
  • the freeze-drying chamber is provided with a plurality of sample tanks. Multiple bottled samples can be placed.
  • the DSC thermal analysis system is composed of a sample stage and a reference stage. It is bolted to the bottom of the freeze-drying chamber by fasteners.
  • the vacuum system includes a vacuum pipe, a vacuum pump, a manual valve, a vacuum gauge and a vent valve; two vacuum pipes are respectively connected to the freeze drying chamber; and a vacuum pump, a manual valve and a vacuum gauge are connected to the vacuum pipe connected to the freeze drying chamber.
  • a vent valve is connected to another vacuum line connected to the freeze drying chamber.
  • the temperature measuring thermocouple wire is installed on the sample table and the reference table, the temperature measuring thermocouple wire is connected to the temperature recorder, and the temperature recorder is connected to the computer.
  • the residual moisture measuring system refers to a humidity sensor.
  • the freeze-drying device of the present invention is suitable for freeze-drying research of heat sensitive substances such as biological products and medicines, and can not only utilize DSC in the pre-freezing stage.
  • the thermal analysis function measures the thermal effect of the freezing system and analyzes the pre-freezing quality. It can also observe the ice crystal formation size and ice crystal sublimation in the freeze-drying system in real time through the microscopic camera system in the sublimation drying stage, and freeze-dry the heat sensitive substances such as biological products and medicines.
  • Technology provides a comprehensive research platform.
  • Figure 1 is a vacuum freeze-drying device with DSC and microstructure observation function of Example 1.
  • Figure 2 is a schematic view showing the structure of the freeze-drying chamber of the first embodiment.
  • the vacuum freeze-drying device with DSC and microstructure observation function consists of a freeze-drying system, a vacuum system, DSC thermal analysis system, micro camera system, residual moisture measurement system and computer.
  • the freeze-drying system includes a freeze drying chamber 1, a heating device, and a refrigerating device.
  • Freeze drying room 1 It is a closed container with a transparent sealing cover 17 on the wall of the container, and the freeze drying chamber 1 is fixed on the bracket 2 to avoid sliding during operation. .
  • the heating device comprises an electric heating wire 6 and a thermostat 7
  • the electric heating wire 6 is wound around the outer surface of the freeze-drying chamber 1 and connected to the thermostat 7, and during the cooling process, the temperature of the freeze-drying chamber 1 is also controlled, so in the freeze-drying chamber 1
  • the outer surface of the container is evenly wound around the electric heating wire 6, which is controlled by the thermostat 7, and the heating power is adjusted according to the set temperature program, thereby consuming excessive cooling input by liquid nitrogen to achieve freezing Drying room 1 Heating or constant temperature control of the sample.
  • a plurality of sample tanks 22 are provided in the freeze-drying chamber 1, and the bottled sample to be tested is placed in the sample tank 22.
  • the refrigeration device includes a heat transfer rod 3 and liquid nitrogen 5, a heat transfer rod 3 and liquid nitrogen 5 are both disposed under the support 2, the bottom of the freeze-drying chamber 1 is connected to one end of the heat transfer rod 3, and the other end of the heat transfer rod 3 is immersed in the liquid nitrogen 5 to transfer the cold amount to the freeze-drying chamber 1 And to cool and freeze the sample in the freeze-drying chamber 1 .
  • the liquid nitrogen 5 is disposed on the lifting platform 4, and the depth at which the heat transfer rod 3 is immersed in the liquid nitrogen 5 can be freely adjusted by the lifting table 4.
  • the freeze drying chamber 1 is connected to a vacuum system; the vacuum system includes a vacuum pipe 8 16 , a vacuum pump 9 , a manual valve 10 , a vacuum gauge 11 and vent valve 15; vacuum line 8 16 is connected to freeze-drying chamber 1 respectively; vacuum pump 8 connected to freeze-drying chamber 1 is connected with vacuum pump 9 , manual valve 10 and vacuum gauge 11 , another vacuum line 16 connected to the freeze drying chamber 1 is connected with a vent valve 15 , and when the vent valve 15 is opened, the freeze drying chamber 1 is filled with air.
  • manual valve 10 When closed, the sample in the freeze-drying chamber 1 can be protected from contamination from the vacuum pump 9 and the external environment.
  • the DSC thermal analysis system is located inside the freeze drying chamber 1; the DSC thermal analysis system consists of a sample stage 18 and a reference stage 19 It is composed and bolted to the bottom of the freeze-drying chamber 1 by fasteners 21.
  • a temperature measuring thermocouple wire 20 and a thermocouple thermocouple wire 20 are respectively mounted on the sample stage 18 and the reference table 19. Put out the freeze drying chamber 1 Connect the temperature recorder 14 , the temperature recorder 14 and then connect the computer 13 .
  • the sample undergoes phase change crystallization and ice crystal sublimation in the pre-freezing stage and the sublimation drying stage, heat release and heat capacity change occur, causing a change in the local temperature on the sample stage.
  • the temperature measurement thermoelectricity on the sample stage is passed. Even line 20 This temperature change of the sample stage relative to the reference stage can be detected and the data displayed on the temperature recorder and then transferred to the computer 13 for data storage.
  • the micro camera system 12 is located outside the freeze drying chamber 1.
  • Freeze drying chamber 1 container sealing cover 17 Made of a transparent material, the microstructure of the sample in the freeze-drying chamber 1 can be captured by the microscopic camera system 12 mounted above the container of the freeze-drying chamber 1 through the transparent sealing cover 17, and the data is stored in the computer. 13 .
  • the residual moisture measuring system is disposed inside the freeze drying chamber 1; the residual moisture measuring system refers to a humidity sensor 23 and a humidity sensor 23
  • the water vapor partial pressure in the freeze drying chamber 1 can be measured, and the data is transmitted to the humidity display meter through the data line 24, and then stored in the computer 13 and finally according to the freeze drying chamber 1
  • the change in the partial pressure of water vapor inside can be used to calculate the change in the concentration of residual moisture in the lyophilized material.

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  • Combustion & Propulsion (AREA)
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  • Chemical Kinetics & Catalysis (AREA)
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Abstract

Disclosed is a vacuum freeze-drying apparatus which consists of a freeze-drying system, a vacuum system, a DSC thermal-analysis system, a microscopic imaging system, a residual moisture measuring system and a computer (13). The freeze-drying system comprises a freeze-drying chamber (1), a heating device and a refrigeration device, wherein the freeze-drying chamber is a closed container, on the wall of which a transparent part (17) is arranged, and the heating device and the refrigeration device are arranged on the freeze-drying chamber (1). The DSC thermal-analysis system and the residual moisture measuring system are provided inside the freeze-drying chamber (1), while the microscopic imaging system is provided outside the freeze-drying chamber (1). Each system is connected with the computer (13) respectively. The invention is suitable for the freeze-drying research on biological products, medicines and other thermosensitive substances.

Description

[根据细则37.2由ISA制定的发明名称]　真空冷冻干燥装置[Name of invention established by ISA according to Rule 37.2] Vacuum freeze-drying device
技术领域 Technical field
本发明涉及一种真空冷冻干燥装置，具体地说，涉及一种具有 DSC 及微结构观察功能的真空冷冻干燥装置。 The present invention relates to a vacuum freeze-drying apparatus, and more particularly to a vacuum freeze-drying apparatus having a DSC and a microstructure observation function.
背景技术 Background technique
真空冷冻干燥是将含有水的物料在低温下冻结形成冰，然后在真空条件下对冷冻物料加热，使冰升华，从而得到干制品的一种干燥方法。对于生物制品、药品等热敏性物质，为了防止在生产时由于温度过高而使其变性，真空冷冻干燥技术无疑是最为理想的生产加工方法。冻干的生物制品、药品一般都被制成注射剂，为了其贮存和使用的方便，通常采用瓶装物料冻干的形式。 Vacuum freeze-drying is a drying method in which a material containing water is frozen at a low temperature to form ice, and then the frozen material is heated under vacuum to sublimate the ice to obtain a dry product. For heat-sensitive substances such as biological products and pharmaceuticals, vacuum freeze-drying technology is undoubtedly the most ideal production and processing method in order to prevent denaturation due to excessive temperature during production. Freeze-dried biological products and pharmaceuticals are generally prepared as injections, and for the convenience of storage and use, the lyophilized form of the bottled materials is usually used.
冻干机是真空冷冻干燥常采用的装置，由于其加热隔板与瓶装物料的接触面积小，使得传热往往成为冻干过程的主要控制步骤，并且升华界面均匀地向瓶底移动的一维传热模型成为实验和生产的主要指导模型。一维传热模型忽略了瓶侧面的热量传入，然而在实际中，瓶装物料的厚度与瓶颈大小可以相比拟，其径向传热对冻干过程的影响是不可忽略的。此外，冻干过程的影响因素较多且相互关联，因此只能通过实验研究的方法来获得适宜的冻干参数和工艺。 The lyophilizer is a device commonly used in vacuum freeze-drying. Because of the small contact area between the heating separator and the bottled material, heat transfer tends to be the main control step of the freeze-drying process, and the sublimation interface uniformly moves to the bottom of the bottle. The heat transfer model became the main guiding model for experimentation and production. The one-dimensional heat transfer model ignores the heat transfer from the side of the bottle. However, in practice, the thickness of the bottled material can be compared with the bottleneck size, and the effect of radial heat transfer on the freeze-drying process is not negligible. In addition, the influencing factors of the freeze-drying process are more and related, so the experimental parameters can be used to obtain suitable freeze-drying parameters and processes.
成功的冻干过程不仅取决于冻干产品的结构认识，还取决于冻干的热、动力学过程。其中，最常采用的结构研究和热分析的方法是差示扫描量热法 (DSC) ，该方法可以测量样品和传感器探头之间温度变化过程的差异，其热行为被记录下来，根据记录的 DSC 曲线，可以分析冻干样品的冰点、冻结特性以及玻璃化转变特性。此外，显微镜是一种最为直观的结构研究方法，它可以直接观察到被测样品的微观结构。 A successful lyophilization process depends not only on the structural knowledge of the lyophilized product, but also on the heat and kinetics of the lyophilization. Among them, the most commonly used method of structural research and thermal analysis is differential scanning calorimetry (DSC). , the method can measure the difference in temperature change process between the sample and the sensor probe, and its thermal behavior is recorded, according to the recorded DSC Curves allow analysis of the freezing point, freezing characteristics, and glass transition characteristics of lyophilized samples. In addition, the microscope is one of the most intuitive structural research methods, which can directly observe the microstructure of the sample to be tested.
为了能够全面深入地对瓶装生物制品、药品等热敏性物质的冷冻干燥进行研究并获得具有实用价值的数据，以便对其实际生产提供更为有效的参考和指导，需要一种具有 DSC 和微结构观察功能的真空冷冻干燥装置。 In order to fully and thoroughly study the freeze-drying of heat-sensitive substances such as bottled biological products and pharmaceuticals and obtain practical data to provide more effective reference and guidance for their actual production, a DSC is required. And a vacuum freeze drying device with a microstructure observation function.
发明内容 Summary of the invention
本发明的目的在于提供一种能够实时测量冻干样品热效应和结构变化的真空冷冻干燥装置。 It is an object of the present invention to provide a vacuum freeze-drying apparatus capable of measuring the thermal effect and structural change of a lyophilized sample in real time.
为了实现上述目的，本发明采用如下技术方案： In order to achieve the above object, the present invention adopts the following technical solutions:
一种具有 DSC 及微结构观察功能的真空冷冻干燥装置，由冷冻干燥系统、真空系统、 DSC 热分析系统、 显微摄像系统、残余水分测量系统和计算机组成；所述冷冻干燥系统包括冷冻干燥室、加热器件和制冷器件，冷冻干燥室为一密闭容器，容器壁上设有透明部分，加热器件和制冷器件设于冷冻干燥室上；冷冻干燥室连接真空系统； DSC 热分析系统设于冷冻干燥室内部； 显微摄像系统设于冷冻干燥室外部，可透过冷冻干燥室壁上的透明部分观察内部样品微观结构；残余水分测量系统设于冷冻干燥室内部，通过测量冷冻干燥室内的水汽分压以测量冻干物料的残余水分含量； DSC 热分析系统、显微摄像系统和残余水分测量系统分别与 计算机连接。 A vacuum freeze-drying device with DSC and microstructure observation function, which is a freeze-drying system, a vacuum system, a DSC thermal analysis system, a micro camera system, a residual moisture measuring system and a computer; the freeze drying system comprises a freeze drying chamber, a heating device and a refrigeration device, the freeze drying chamber is a closed container, the container wall is provided with a transparent portion, a heating device and a cooling device Located in the freeze drying chamber; the freeze drying chamber is connected to the vacuum system; The DSC thermal analysis system is located inside the freeze drying chamber; The microscopic camera system is arranged outside the freeze-drying chamber, and the internal sample microstructure can be observed through the transparent portion on the wall of the freeze-drying chamber; the residual moisture measuring system is arranged inside the freeze-drying chamber, and the water vapor partial pressure in the freeze-drying chamber is measured to measure The residual moisture content of the lyophilized material; The DSC thermal analysis system, microscopic camera system, and residual moisture measurement system are each connected to a computer.
在上述具有 DSC 及微结构观察功能的真空冷冻干燥装置中，所述制冷器件包括传热棒和液氮，冷冻干燥室的底部与传热棒一端连接，传热棒的另一端浸入液氮中， 从而将冷量传至干燥室，并以此对干燥室内样品进行降温和冷冻。 Have DSC in the above In the vacuum freeze-drying device with the microstructure observation function, the refrigeration device comprises a heat transfer rod and liquid nitrogen, the bottom of the freeze-drying chamber is connected to one end of the heat transfer rod, and the other end of the heat transfer rod is immersed in liquid nitrogen. Thereby, the cold amount is transferred to the drying chamber, and thereby the sample in the drying chamber is cooled and frozen.
在上述具有 DSC 及微结构观察功能的真空冷冻干燥装置中，所述液氮设于升降台上。 传热棒浸入液氮中的深度可以通过升降台自由调节。 In the above vacuum freeze-drying apparatus having a DSC and microstructure observation function, the liquid nitrogen is provided on a lifting platform. The depth at which the heat transfer rod is immersed in liquid nitrogen can be freely adjusted by the lifting table.
在上述具有 DSC 及微结构观察功能的真空冷冻干燥装置中，所述加热器件包括电加热丝和温控器。电加热丝均匀安装在干燥室容器外表面，通过温控器根据设定的温度程序来调节加热功率，为冷冻干燥室内样品提供热源。 Have DSC in the above In the vacuum freeze-drying device of the microstructure observation function, the heating device comprises an electric heating wire and a thermostat. The electric heating wire is evenly installed on the outer surface of the drying chamber container, and the heating power is adjusted according to the set temperature program by the thermostat to provide a heat source for the sample in the freeze-drying chamber.
在上述具有 DSC 及微结构观察功能的真空冷冻干燥装置中，所述冷冻干燥室内设有多个样品槽， 可以放置多个瓶装样品。 In the above vacuum freeze-drying apparatus having the DSC and the microstructure observation function, the freeze-drying chamber is provided with a plurality of sample tanks. Multiple bottled samples can be placed.
在上述具有 DSC 及微结构观察功能的真空冷冻干燥装置中， 所述 DSC 热分析系统由样品台和参比台组成， 并通过紧固件用螺栓固定在冷冻干燥室的底部上。 In the above vacuum freeze-drying apparatus having the DSC and microstructure observation function, the DSC thermal analysis system is composed of a sample stage and a reference stage. It is bolted to the bottom of the freeze-drying chamber by fasteners.
在上述具有 DSC 及微结构观察功能的真空冷冻干燥装置中， 所述真空系统包括真空管道、真空泵、手动阀、真空计和放空阀；真空管道有两条，分别与冷冻干燥室连接；与冷冻干燥室连接的真空管道上连接有真空泵、手动阀和真空计，与冷冻干燥室连接的另一真空管道上连接有放空阀。 In the above vacuum freeze-drying device with DSC and microstructure observation function, The vacuum system includes a vacuum pipe, a vacuum pump, a manual valve, a vacuum gauge and a vent valve; two vacuum pipes are respectively connected to the freeze drying chamber; and a vacuum pump, a manual valve and a vacuum gauge are connected to the vacuum pipe connected to the freeze drying chamber. A vent valve is connected to another vacuum line connected to the freeze drying chamber.
在上述具有 DSC 及微结构观察功能的真空冷冻干燥装置中， 所述样品台和参比台上分别安装有测温热电偶线，测温热电偶线连接温度记录仪，温度记录仪再连接计算机。 In the above vacuum freeze-drying device with DSC and microstructure observation function, The temperature measuring thermocouple wire is installed on the sample table and the reference table, the temperature measuring thermocouple wire is connected to the temperature recorder, and the temperature recorder is connected to the computer.
在上述具有 DSC 及微结构观察功能的真空冷冻干燥装置中， 所述 容器壁上设有透明部分是指冷冻干燥室采用透明的密封盖。 In the above vacuum freeze-drying apparatus having DSC and microstructure observation function, The provision of a transparent portion on the wall of the container means that the freeze-drying chamber is provided with a transparent sealing cover.
在上述具有 DSC 及微结构观察功能的真空冷冻干燥装置中， 所述残余水分测量系统是指湿度传感器。 In the above vacuum freeze-drying apparatus having a DSC and microstructure observation function, the residual moisture measuring system refers to a humidity sensor.
与现有技术相比，本发明具有如下有益效果：本发明的冷冻干燥装置适用于生物制品、药品等热敏性物质的冷冻干燥研究，不仅能够在预冻阶段利用 DSC 热分析功能测量冷冻体系的热效应并分析预冻质量，还能够在升华干燥阶段通过显微摄像系统实时观察冻干体系中冰晶形成大小和冰晶升华情况，为生物制品、药品等热敏性物质的冷冻干燥技术提供一种全面的研究平台。 Compared with the prior art, the present invention has the following beneficial effects: the freeze-drying device of the present invention is suitable for freeze-drying research of heat sensitive substances such as biological products and medicines, and can not only utilize DSC in the pre-freezing stage. The thermal analysis function measures the thermal effect of the freezing system and analyzes the pre-freezing quality. It can also observe the ice crystal formation size and ice crystal sublimation in the freeze-drying system in real time through the microscopic camera system in the sublimation drying stage, and freeze-dry the heat sensitive substances such as biological products and medicines. Technology provides a comprehensive research platform.
附图说明 DRAWINGS
图 1 是实施例 1 具有 DSC 及微结构观察功能的真空冷冻干燥装置 Figure 1 is a vacuum freeze-drying device with DSC and microstructure observation function of Example 1.
结构示意图。 Schematic.
图 2 是实施例 1 的冷冻干燥室结构示意图 。 Figure 2 is a schematic view showing the structure of the freeze-drying chamber of the first embodiment.
具体实施方式 detailed description
实施例 1 Example 1
如图 1 和图 2 所示，具有 DSC 及微结构观察功能的真空冷冻干燥装置，由冷冻干燥系统、真空系统、 DSC 热分析系统、显微摄像系统、残余水分测量系统和计算机组成。 As shown in Figure 1 and Figure 2, the vacuum freeze-drying device with DSC and microstructure observation function consists of a freeze-drying system, a vacuum system, DSC thermal analysis system, micro camera system, residual moisture measurement system and computer.
所述冷冻干燥系统包括冷冻干燥室 1 、加热器件和制冷器件。冷冻干燥室 1 为一密闭容器，容器壁上采用透明的密封盖 17 ，冷冻干燥室 1 固定在支架 2 上， 避免在操作时滑动。 。 所述加热器件包括电加热丝 6 和温控器 7 ，电加热丝 6 缠绕在冷冻干燥室 1 外表面，并与温控器 7 连接，在降温过程中，还需要对冷冻干燥室 1 进行温度控制，因此在冷冻干燥室 1 的容器外表面均匀缠绕电加热丝 6 ，该电加热丝 6 通过温控器 7 控制，根据设定的温度程序来调节加热功率，从而消耗由液氮输入的过多冷量，以实现对冷冻干燥室 1 内样品的加热或恒温控制。冷冻干燥室 1 内设有多个样品槽 22 ，待检测的瓶装样品就设于样品槽 22 中。所述制冷器件包括传热棒 3 和液氮 5 ，传热棒 3 和液氮 5 均设于支架 2 底下，冷冻干燥室 1 的底部与传热棒 3 一端连接，传热棒 3 的另一端浸入液氮 5 中，以将冷量传至冷冻干燥室 1 ，并以此对冷冻干燥室 1 内样品进行降温和冷冻。所述液氮 5 设于升降台 4 上，传热棒 3 浸入液氮 5 中的深度可以通过升降台 4 自由调节。 The freeze-drying system includes a freeze drying chamber 1, a heating device, and a refrigerating device. Freeze drying room 1 It is a closed container with a transparent sealing cover 17 on the wall of the container, and the freeze drying chamber 1 is fixed on the bracket 2 to avoid sliding during operation. . The heating device comprises an electric heating wire 6 and a thermostat 7 The electric heating wire 6 is wound around the outer surface of the freeze-drying chamber 1 and connected to the thermostat 7, and during the cooling process, the temperature of the freeze-drying chamber 1 is also controlled, so in the freeze-drying chamber 1 The outer surface of the container is evenly wound around the electric heating wire 6, which is controlled by the thermostat 7, and the heating power is adjusted according to the set temperature program, thereby consuming excessive cooling input by liquid nitrogen to achieve freezing Drying room 1 Heating or constant temperature control of the sample. A plurality of sample tanks 22 are provided in the freeze-drying chamber 1, and the bottled sample to be tested is placed in the sample tank 22. The refrigeration device includes a heat transfer rod 3 and liquid nitrogen 5, a heat transfer rod 3 and liquid nitrogen 5 are both disposed under the support 2, the bottom of the freeze-drying chamber 1 is connected to one end of the heat transfer rod 3, and the other end of the heat transfer rod 3 is immersed in the liquid nitrogen 5 to transfer the cold amount to the freeze-drying chamber 1 And to cool and freeze the sample in the freeze-drying chamber 1 . The liquid nitrogen 5 is disposed on the lifting platform 4, and the depth at which the heat transfer rod 3 is immersed in the liquid nitrogen 5 can be freely adjusted by the lifting table 4.
冷冻干燥室 1 连接真空系统； 所述真空系统包括真空管道 8 16 、真空泵 9 、手动阀 10 、真空计 11 和放空阀 15 ；真空管道 8 16 分别与冷冻干燥室 1 连接；与冷冻干燥室 1 连接的真空管道 8 上连接有真空泵 9 、手动阀 10 和真空计 11 ，与冷冻干燥室 1 连接的另一真空管道 16 上连接有放空阀 15 ，打开放空阀 15 时对冷冻干燥室 1 充入空气。当手动阀 10 关闭时可以保护冷冻干燥室 1 内样品免受来自真空泵 9 及外部环境的污染。 The freeze drying chamber 1 is connected to a vacuum system; the vacuum system includes a vacuum pipe 8 16 , a vacuum pump 9 , a manual valve 10 , a vacuum gauge 11 and vent valve 15; vacuum line 8 16 is connected to freeze-drying chamber 1 respectively; vacuum pump 8 connected to freeze-drying chamber 1 is connected with vacuum pump 9 , manual valve 10 and vacuum gauge 11 , another vacuum line 16 connected to the freeze drying chamber 1 is connected with a vent valve 15 , and when the vent valve 15 is opened, the freeze drying chamber 1 is filled with air. When manual valve 10 When closed, the sample in the freeze-drying chamber 1 can be protected from contamination from the vacuum pump 9 and the external environment.
DSC 热分析系统设于冷冻干燥室 1 内部；所述 DSC 热分析系统由样品台 18 和参比台 19 组成，并通过紧固件 21 用螺栓固定在冷冻干燥室 1 的底部上。所述样品台 18 和参比台 19 上分别安装有测温热电偶线 20 ，测温热电偶线 20 穿出冷冻干燥室 1 连接温度记录仪 14 ，温度记录仪 14 再连接计算机 13 。当样品在预冻阶段和升华干燥阶段发生相变结晶和冰晶升华时，会产生热量的释放和热容的变化，从而引起样品台上局部温度的变化，此时通过样品台上的测温热电偶线 20 便能够检测到样品台相对于参比台的这一温度变化过程，并将数据显示在温度记录仪上，然后传输至计算机 13 中进行数据保存。 The DSC thermal analysis system is located inside the freeze drying chamber 1; the DSC thermal analysis system consists of a sample stage 18 and a reference stage 19 It is composed and bolted to the bottom of the freeze-drying chamber 1 by fasteners 21. A temperature measuring thermocouple wire 20 and a thermocouple thermocouple wire 20 are respectively mounted on the sample stage 18 and the reference table 19. Put out the freeze drying chamber 1 Connect the temperature recorder 14 , the temperature recorder 14 and then connect the computer 13 . When the sample undergoes phase change crystallization and ice crystal sublimation in the pre-freezing stage and the sublimation drying stage, heat release and heat capacity change occur, causing a change in the local temperature on the sample stage. At this time, the temperature measurement thermoelectricity on the sample stage is passed. Even line 20 This temperature change of the sample stage relative to the reference stage can be detected and the data displayed on the temperature recorder and then transferred to the computer 13 for data storage.
显微摄像系统 12 设于冷冻干燥室 1 外部。冷冻 干燥室 1 容器的密封盖 17 采用透明材料制成，通过透明密封盖 17 ，可以由安装在冷冻干燥室 1 容器上方的显微摄像系统 12 拍摄到冷冻干燥室 1 内样品的微观结构，并将数据存入计算机 13 。 The micro camera system 12 is located outside the freeze drying chamber 1. Freeze drying chamber 1 container sealing cover 17 Made of a transparent material, the microstructure of the sample in the freeze-drying chamber 1 can be captured by the microscopic camera system 12 mounted above the container of the freeze-drying chamber 1 through the transparent sealing cover 17, and the data is stored in the computer. 13 .
残余水分测量系统设于冷冻干燥室 1 内部；所述残余水分测量系统是指湿度传感器 23 ，湿度传感器 23 能测量冷冻干燥室 1 内的水汽分压，并通过数据线 24 将数据传输至湿度显示仪表，然后存入计算机 13 ，最后根据冷冻干燥室 1 内的水汽分压变化，可计算得到冻干物料中残余水分的浓度变化。 The residual moisture measuring system is disposed inside the freeze drying chamber 1; the residual moisture measuring system refers to a humidity sensor 23 and a humidity sensor 23 The water vapor partial pressure in the freeze drying chamber 1 can be measured, and the data is transmitted to the humidity display meter through the data line 24, and then stored in the computer 13 and finally according to the freeze drying chamber 1 The change in the partial pressure of water vapor inside can be used to calculate the change in the concentration of residual moisture in the lyophilized material.

Claims (7)

  1. 具有 DSC 及微结构观察功能的真空冷冻干燥装置，其特征在于由冷冻干燥系统、真空系统、 DSC 热分析系统、 显微摄像系统、残余水分测量系统和计算机组成；所述冷冻干燥系统包括冷冻干燥室、加热器件和制冷器件，冷冻干燥室为一密闭容器，容器壁上设有透明部分，加热器件和制冷器件设于冷冻干燥室上；冷冻干燥室连接真空系统； DSC 热分析系统设于冷冻干燥室内部； 显微摄像系统设于冷冻干燥室外部，可透过冷冻干燥室壁上的透明部分观察内部样品微观结构；残余水分测量系统设于冷冻干燥室内部，通过测量冷冻干燥室内的水汽分压以测量冻干物料的残余水分含量； DSC 热分析系统、显微摄像系统和残余水分测量系统分别与 计算机连接。A vacuum freeze-drying device with DSC and microstructure observation function, characterized by a freeze-drying system, a vacuum system, a DSC thermal analysis system, a micro camera system, a residual moisture measuring system and a computer; the freeze drying system comprises a freeze drying chamber, a heating device and a refrigeration device, the freeze drying chamber is a closed container, the container wall is provided with a transparent portion, a heating device and a cooling device Located in the freeze drying chamber; the freeze drying chamber is connected to the vacuum system; The DSC thermal analysis system is located inside the freeze drying chamber; The microscopic camera system is arranged outside the freeze-drying chamber, and the internal sample microstructure can be observed through the transparent portion on the wall of the freeze-drying chamber; the residual moisture measuring system is arranged inside the freeze-drying chamber, and the water vapor partial pressure in the freeze-drying chamber is measured to measure The residual moisture content of the lyophilized material; The DSC thermal analysis system, microscopic camera system, and residual moisture measurement system are each connected to a computer.
  2. 按照权利要求 1 所述的具有 DSC 及微结构观察功能的真空冷冻干燥装置，其特征在于所述冷冻干燥室内设有多个样品槽。 A vacuum freeze-drying apparatus having a DSC and a microstructure observation function according to claim 1, wherein said freeze-drying chamber is provided with a plurality of sample tanks.
  3. 按照权利要求 1 所述的具有 DSC 及微结构观察功能的真空冷冻干燥装置，其特征在于所述 DSC 热分析系统由样品台和参比台组成， 并通过紧固件固定在冷冻干燥室的底部上。
    A vacuum freeze-drying apparatus with DSC and microstructure observation function according to claim 1, wherein said DSC thermal analysis system is composed of a sample stage and a reference table, and is fixed to the bottom of the freeze-drying chamber by fasteners. on.
  4. 按照权利要求 1 所述的具有 DSC 及微结构观察功能的真空冷冻干燥装置，其特征在于所述真空系统包括真空管道、真空泵、手动阀、真空计和放空阀；真空管道有两条，分别与冷冻干燥室连接；与冷冻干燥室连接的真空管道上连接有真空泵、手动阀和真空计，与冷冻干燥室连接的另一真空管道上连接有放空阀。DSC according to claim 1 And a vacuum freeze-drying device with a microstructure observation function, characterized in that the vacuum system comprises a vacuum pipe, a vacuum pump, a manual valve, a vacuum gauge and a vent valve; two vacuum pipes are respectively connected to the freeze-drying chamber; and the freeze-drying chamber A vacuum pump, a manual valve, and a vacuum gauge are connected to the connected vacuum pipe, and a vent valve is connected to another vacuum pipe connected to the freeze-drying chamber.
  5. 按照权利要求 3 所述的具有 DSC 及微结构观察功能的真空冷冻干燥装置，其特征在于所述样品台和参比台上分别安装有测温热电偶线，测温热电偶线连接温度记录仪，温度记录仪再连接计算机。 DSC according to claim 3 The vacuum freeze-drying device with the microstructure observation function is characterized in that the temperature measuring thermocouple wire is installed on the sample table and the reference table, the temperature measuring thermocouple wire is connected to the temperature recorder, and the temperature recorder is connected to the computer.
  6. 按照权利要求 1 所述的具有 DSC 及微结构观察功能的真空冷冻干燥装置，其特征在于所述 容器壁上设有透明部分是指冷冻干燥室采用透明的密封盖。A vacuum freeze-drying apparatus having DSC and microstructure observation function according to claim 1, wherein said vacuum drying apparatus is characterized by The provision of a transparent portion on the wall of the container means that the freeze-drying chamber is provided with a transparent sealing cover.
  7. 按照权利要求 1 所述的具有 DSC 及微结构观察功能的真空冷冻干燥装置，其特征在于所述残余水分测量系统是指湿度传感器。
    A vacuum freeze-drying apparatus having a DSC and microstructure observation function according to claim 1, wherein said residual moisture measuring system is a humidity sensor.
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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2551687A (en) * 2016-03-04 2018-01-03 Linkam Scient Instruments Ltd Freeze drying apparatus
CN110108690A (en) * 2019-06-10 2019-08-09 中国科学院生物物理研究所 A kind of ultralow temperature can vary micro imaging system and its working method

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101793458B (en) * 2010-04-02 2012-03-21 中山大学 Vacuum freezing drying device with functions of DSC and microstructure observation
WO2015024141A1 (en) * 2013-08-22 2015-02-26 国玺干细胞应用技术股份有限公司 Biological product storage device provided with observation element
CN107568558B (en) 2017-10-31 2021-02-02 王一田 Steam pasteurization of freeze-dried food products
CN110057821B (en) * 2019-04-16 2021-09-07 上海交通大学 Low-temperature microscopic imaging system for human gamete rapid freeze-thawing process observation
CN110132791B (en) * 2019-05-17 2021-11-26 杭州仰仪科技有限公司 Cold-conducting vibration-isolating sample container for testing low-temperature fluidity of liquid
CN110530925A (en) * 2019-08-08 2019-12-03 西安交通大学 A kind of DSC heat analysis method applying electric field action

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH09229884A (en) * 1996-02-21 1997-09-05 Shimadzu Corp Thermal analysis apparatus
CN1818738A (en) * 2006-03-10 2006-08-16 浙江大学 Microscope observation system during freezing dry process
CN201083735Y (en) * 2007-06-26 2008-07-09 上海理工大学 Low-temperature microscopic differential scanning calorimetry system main apparatus
CN101419015A (en) * 2008-09-02 2009-04-29 上海理工大学 Method for judging once lyophilization drying end point and secondary drying end point
CN201387412Y (en) * 2009-03-24 2010-01-20 山西农业大学 Water content online monitoring device during freeze drying process of fresh products
CN101793458A (en) * 2010-04-02 2010-08-04 中山大学 Vacuum freezing drying device with functions of DSC and microstructure observation
CN201615678U (en) * 2010-04-02 2010-10-27 中山大学 Vacuum freeze drying device with DSC and microstructure observation functions

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH09229884A (en) * 1996-02-21 1997-09-05 Shimadzu Corp Thermal analysis apparatus
CN1818738A (en) * 2006-03-10 2006-08-16 浙江大学 Microscope observation system during freezing dry process
CN201083735Y (en) * 2007-06-26 2008-07-09 上海理工大学 Low-temperature microscopic differential scanning calorimetry system main apparatus
CN101419015A (en) * 2008-09-02 2009-04-29 上海理工大学 Method for judging once lyophilization drying end point and secondary drying end point
CN201387412Y (en) * 2009-03-24 2010-01-20 山西农业大学 Water content online monitoring device during freeze drying process of fresh products
CN101793458A (en) * 2010-04-02 2010-08-04 中山大学 Vacuum freezing drying device with functions of DSC and microstructure observation
CN201615678U (en) * 2010-04-02 2010-10-27 中山大学 Vacuum freeze drying device with DSC and microstructure observation functions

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
ZUO JIANGUO ET AL: "Cryomicroscopy and Thermal Analysis of Solution for Freeze-drying", JOURNAL OF ENGINEERING THERMOPHYSICS, vol. 27, no. 2, March 2006 (2006-03-01), pages 307 - 308 *
ZUO JIANGUO ET AL: "Study of the Freezing Properties of Solutions for Freeze-drying by DSC", CRYOGENICS, no. 145, June 2005 (2005-06-01), pages 48 - 51 *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2551687A (en) * 2016-03-04 2018-01-03 Linkam Scient Instruments Ltd Freeze drying apparatus
CN110108690A (en) * 2019-06-10 2019-08-09 中国科学院生物物理研究所 A kind of ultralow temperature can vary micro imaging system and its working method
CN110108690B (en) * 2019-06-10 2023-11-24 中国科学院生物物理研究所 Ultralow-temperature sample-changeable microscopic imaging system and working method thereof

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