WO2020161863A1 - Procédé de lyophylisation sous vide et dispositif de séchage par congélation sous vide - Google Patents

Procédé de lyophylisation sous vide et dispositif de séchage par congélation sous vide Download PDF

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Publication number
WO2020161863A1
WO2020161863A1 PCT/JP2019/004442 JP2019004442W WO2020161863A1 WO 2020161863 A1 WO2020161863 A1 WO 2020161863A1 JP 2019004442 W JP2019004442 W JP 2019004442W WO 2020161863 A1 WO2020161863 A1 WO 2020161863A1
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WO
WIPO (PCT)
Prior art keywords
raw material
vacuum
material liquid
drying
injection nozzle
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Application number
PCT/JP2019/004442
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English (en)
Japanese (ja)
Inventor
美尚 中野
勉 西橋
剛 吉元
薫樹 伊藤
野末　竜弘
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株式会社アルバック
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Priority to PCT/JP2019/004442 priority Critical patent/WO2020161863A1/fr
Publication of WO2020161863A1 publication Critical patent/WO2020161863A1/fr

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    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F26—DRYING
    • F26B—DRYING SOLID MATERIALS OR OBJECTS BY REMOVING LIQUID THEREFROM
    • F26B17/00—Machines or apparatus for drying materials in loose, plastic, or fluidised form, e.g. granules, staple fibres, with progressive movement
    • F26B17/10—Machines or apparatus for drying materials in loose, plastic, or fluidised form, e.g. granules, staple fibres, with progressive movement with movement performed by fluid currents, e.g. issuing from a nozzle, e.g. pneumatic, flash, vortex or entrainment dryers
    • 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

Definitions

  • the present invention relates to the technical field of a vacuum freeze-drying apparatus, and more particularly to a technology for producing a powder by dripping and spraying a liquid such as a chemical solution in a vacuum and freeze-drying.
  • microdroplets are formed and evaporated in a vacuum with a low water pressure, so the latent heat can freeze at ultra-high speeds of less than 1 second, and the ice crystals are also miniaturized.
  • the feature is that
  • Freeze-drying in a vacuum atmosphere does not cause deterioration of foods due to water content or dilution of pharmaceuticals, and high-quality drying can be performed.However, since solid water is vaporized and dried, Since the amount of vaporization also increases due to the rise, conventionally, in order to shorten the drying time, it is necessary to deposit frozen powder on a metal tray in a vacuum tank and heat the metal tray to heat the frozen powder to dry it. Is being done.
  • Patent Document 1 Japanese Patent Laid-Open No. 2004-232883 describes a mass production method of forming atomized frozen powder of a chemical solution or the like in a vacuum and sublimating and drying it, but it depends on conditions of each step. Then, there is a concern that the device will become large and the cost of mass production will increase.
  • the present invention has been made in view of the problems of the conventional techniques as described above, and an object of the present invention is to make it possible to freeze the liquid droplets of the raw material liquid in a short time and with a short drop distance, and to perform mass production in a small size. To provide a simple vacuum freeze-drying device.
  • the present invention was created in order to solve the above-mentioned problems of the prior art, and the present invention made to achieve the above-mentioned object is to spray a raw material liquid in a vacuum tank from a spray nozzle and spray it under a low temperature vacuum.
  • a method of vacuum freeze-drying comprising the steps of: producing frozen fine particles by self-freezing in step 1, and drying the produced frozen fine particles to produce a dry powder, wherein the water vapor partial pressure in the vacuum tank is maintained at 60 Pa or less.
  • the diameter of the droplet of the raw material liquid dropped from the injection nozzle is adjusted to 1000 ⁇ m or less, and the initial velocity of the droplet is adjusted to 8 m/sec or more and 22 m/sec or less. It has a process.
  • the raw material liquid contains a solvent or dispersion medium composed of water with a content of 70% by weight or more, and a solute dissolved in the solvent or a dispersoid dispersed in the dispersion medium.
  • the solute or the dispersoid of the raw material liquid is a raw material of a freeze-dried food in which cells are not destroyed and proteins are not denatured during vacuum freeze-drying, or a drug as an active ingredient of a preparation. Is also effective.
  • a vacuum tank in which a container for storing frozen fine particles can be arranged, and a droplet of a raw material liquid, which is provided in the vacuum tank and contains 70% by weight or more of water supplied from a raw material tank, is dropped and sprayed.
  • Injection nozzle a raw material tank for supplying the raw material liquid to the injection nozzle, a cold trap for removing water in the vacuum chamber, and heating for drying the frozen fine particles contained in the container.
  • a cold trap for maintaining the partial pressure of water vapor in the vacuum tank at 60 Pa or less based on the result obtained by a vacuum gauge connected to the vacuum tank when the raw material liquid is dropped.
  • An exhaust amount adjusting device for adjusting the exhaust amount is also provided, and the hole diameter of the injection nozzle is adjusted so that the diameter of the droplet of the raw material liquid dropped from the injection nozzle is 1000 ⁇ m or less.
  • the raw material liquid supply amount adjusting device adjusts the initial velocity of the liquid droplets of the raw material liquid dropped from the jet nozzle to 8 m/sec or more and 22 m/sec or less with respect to the jet nozzle.
  • the vacuum freeze-drying device is configured to adjust the supply amount of the raw material liquid.
  • a freezing chamber configured by the vacuum chamber for freezing the liquid droplets of the raw material liquid, and a drying chamber connected to the freezing chamber via a gate valve to dry the frozen fine particles contained in the container It is also effective when having and.
  • the diameter of the droplet of the raw material liquid dropped from the injection nozzle is 1000 ⁇ m or less, and By adjusting the initial velocity to 8 m/sec or more and 22 m/sec or less, the liquid droplets of the raw material liquid can be frozen in a short time and with a shorter drop distance than the conventional technology, which allows for small-scale mass production.
  • a vacuum freeze-drying device can be provided.
  • FIG. 1 is a schematic configuration diagram showing an entire embodiment of a vacuum freeze-drying apparatus according to the present invention.
  • the vacuum freeze-drying apparatus 1 of the present embodiment includes a freezing chamber 2 connected to a vacuum exhaust device 10 via an exhaust volume adjusting device 13, and a freezing chamber 2 via a gate valve 5 to the freezing chamber 2. And a drying chamber 3 connected thereto.
  • the freezing chamber 2 is connected to a carry-in chamber (not shown), and the drying chamber 3 is provided with a vent valve (not shown) for recompressing (opening to the atmosphere).
  • a vacuum gauge 11 for measuring the pressure inside the freezing chamber 2 is connected to the freezing chamber 2.
  • a raw material tank 9 in which a raw material liquid at room temperature is stored is arranged outside the freezing chamber 2, and an injection nozzle 20 connected to the raw material tank 9 is provided above the freezing chamber 2.
  • the raw material liquid is supplied to the injection nozzle 20 from the raw material tank 9 via the raw material liquid supply amount adjusting device 12, and the raw material liquid is sprayed downward in a vacuum atmosphere in a liquid column shape from the lower end portion of the injection nozzle 20. Has become.
  • a cold trap 6 connected to a refrigerator (not shown) is provided near the injection nozzle 20.
  • the raw material liquid may be, for example, a solvent made of water and a solute dissolved in the solvent, or a dispersion medium made of water and a dispersoid dispersed in the dispersion medium.
  • the concentration of water used as the solvent and the dispersion medium is preferably set to 70% by weight or more.
  • a solvent or dispersion medium consisting of 70% by weight of water, a solute dissolved in this solvent, or a liquid containing the dispersoid dispersed in this dispersion medium is preferably used as the raw material liquid. it can.
  • solutes or dispersoids examples include raw materials for freeze-dried foods in which cells are not destroyed and proteins and the like are not denatured during vacuum freeze-drying, and drugs (medicines) as active ingredients of preparations.
  • the tray 7 for containing the generated frozen fine particles 35 is arranged below the injection nozzle 20 inside the freezing chamber 2.
  • the tray 7 is configured to be transferred from the freezing chamber 2 to the drying chamber 3 by using a transfer mechanism such as a robot (not shown).
  • a heating device 8 for drying the frozen fine particles 35 contained in the tray 7, which is, for example, an infrared heater.
  • the vacuum freeze-drying device used in each experiment was a micro-powder dry system, which is a micro-jet freeze-drying device manufactured by ULVAC, Inc.
  • the vacuum exhaust device 10 and the cold trap 6 are operated with the gate valve 5 closed to reduce the pressure in the freezing chamber 2.
  • the inside of the freezing chamber 2 at the time of dropping the raw material liquid is based on the data measured by the vacuum gauge 11 in advance.
  • the partial pressure of water vapor is adjusted to 60 Pa or less.
  • the cold trap 6 and the injection nozzle 20 are operated, and the liquid droplet of the raw material liquid is ejected from the tip of the injection nozzle 20 to be dropped.
  • FIG. 2 is a graph showing the relationship between pressure and temperature of a droplet of water having a diameter (hereinafter referred to as “diameter”) of 300 ⁇ m.
  • the partial pressure of water vapor in the freezing chamber 2 was about 100 Pa, but in the present invention, the partial pressure of water vapor in the freezing chamber 2 is maintained at 60 Pa or less.
  • the partial pressure of water vapor in the freezing chamber 2 is 60 Pa or less, the temperature of the dropped water droplets of 300 ⁇ m diameter is ⁇ 25° C. or less, and as a result, the raw material liquid consisting of water is The droplet can be surely frozen.
  • the exhaust amount is adjusted by the exhaust amount adjusting device 13 and the cold trap 6 so that the partial pressure of water vapor in the freezing chamber 2 is maintained at 60 Pa or less based on the result obtained by the vacuum gauge 11. To do.
  • the cooling time to the desired temperature becomes longer, and the drop distance of the droplet until it reaches -25°C after being cooled increases.
  • FIG. 3 is a graph showing the relationship between the drop distance and the temperature of the droplet with respect to the droplet diameter when the partial pressure of water vapor in the freezing chamber is maintained at 60 Pa and the droplet is dropped at an initial velocity of 13 m/sec.
  • the droplet diameter of the raw material liquid dropped from the injection nozzle 20 is 1000 ⁇ m or less, the drop distance until the droplet is frozen can be reliably 1500 mm or less.
  • the diameter (hole diameter) of the nozzle hole of the injection nozzle 20 for dropping the droplet may be adjusted.
  • FIG. 4 is a graph showing the relationship between the hole diameter of the injection nozzle and the droplet diameter.
  • the droplet diameter of the raw material liquid dropped from the injection nozzle 20 is 1000 ⁇ m or less, the drop distance until the droplet is frozen can be reliably set to 1500 mm or less, which is understood from FIG.
  • the droplet diameter can be set to 600 ⁇ m or less, and thus the drop distance until the freezing of the droplet can be reliably set to less than 1500 mm. ..
  • the initial velocity of the droplets of the raw material liquid dropped from the injection nozzle 20 is adjusted to be 8 m/sec or more and 22 m/sec or less.
  • the present inventor reaches the tray 7 before the liquid droplet is completely frozen even when the liquid droplet is dropped under the above-mentioned conditions. I have found empirically that I will do it.
  • control was performed so that the initial velocity of the liquid droplets of the raw material liquid was 23 m/sec.
  • the raw material liquid in the injection nozzle hole may freeze and the hole may be easily clogged.
  • FIG. 5 is a graph showing the relationship between the spray pressure of the raw material liquid at the injection nozzle and the initial velocity of the liquid droplets.
  • This graph shows the results when a force larger than the surface tension of the raw material liquid is applied to the raw material liquid stored in the liquid storage portion having the hole diameter of the injection nozzle 20 of 0.2 mm and the thickness of the injection nozzle 20 of 0.5 mm. It is the data shown.
  • the initial velocity of the droplet of the raw material liquid dropped from the injection nozzle 20 is 8 m/sec or more and 22 m/sec or less.
  • the raw material liquid supply amount adjusting device 12 adjusts the supply amount (liquid feeding pressure) of the raw material liquid to the injection nozzle 20.
  • the raw material liquid dropped from the injection nozzle 20 becomes a columnar raw material liquid 21 in the initial state of dropping, and thereafter, It is separated from the columnar raw material liquid 21 by the surface tension and becomes a droplet 30 of the raw material liquid.
  • the droplets 30 of the raw material liquid become the droplets 32 in the form of particles through the droplets 31 in the dispersed state as they descend.
  • the particulate droplets 32 are evaporated by the cold trap 6 to adsorb the water in the freezing chamber 2 and self-freezing starts, whereby frozen fine particles 35 are formed.
  • the frozen fine particles 35 are spread in all directions and fall into the tray 7.
  • the tray 7 is carried into the drying chamber 3 by using a transfer mechanism such as a robot (not shown), and the frozen fine particles 35 are heated by the heating device 8 to evaporate the remaining water and dry the same.
  • the diameter of the droplet 30 of the raw material liquid dropped from the injection nozzle 20 is 1000 ⁇ m or less while the partial pressure of water vapor in the freezing chamber 2 is maintained at 60 Pa or less. Moreover, by adjusting the initial velocity of the droplet to be 8 m/sec or more and 22 m/sec or less, the droplet 30 of the raw material liquid can be dropped in a short time and with a shorter fall distance (1500 mm or less) as compared with the conventional technique.
  • the vacuum freeze-drying apparatus 1 that can be frozen and can be mass-produced can be provided.
  • the freezing chamber 2 and the drying chamber 3 are connected via the gate valve 5, but the present invention is not limited to this, and a heating device for drying frozen fine particles in one vacuum tank. Can be provided.
  • the cold trap 6 is provided in the freezing chamber 2 in the above-described embodiment, the present invention is not limited to this, and the cold trap is arranged in a chamber different from the freezing chamber, and the cold trap 6 and the freezing chamber are separated from each other. Can also be configured to connect.

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  • Engineering & Computer Science (AREA)
  • Mechanical Engineering (AREA)
  • General Engineering & Computer Science (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Molecular Biology (AREA)
  • Freezing, Cooling And Drying Of Foods (AREA)
  • Drying Of Solid Materials (AREA)

Abstract

L'invention porte sur un dispositif compact de lyophilisation sous vide, produit en masse, capable de congeler des gouttelettes d'une matière première liquide à une courte distance de chute en peu de temps. Le procédé de lyophilisation sous vide selon la présente invention comprend une étape de production d'une poudre sèche par : pulvérisation de gouttelettes d'une matière première liquide par une buse d'injection (20) dans une chambre de congélation (2) qui est un réservoir sous vide ; génération de fines particules congelées (35) par congélation automatique sous vide à basse température ; et séchage des fines particules congelées générées (35). Dans la présente invention, le diamètre des gouttelettes de la matière première liquide rejetée vers le bas par la buse d'injection (20) est réglé à 1 000 µm ou moins, et la vitesse initiale des gouttelettes est réglée à 8 à 22 m/seconde, dans un état où la pression partielle de la vapeur d'eau dans la chambre de congélation (2) est maintenue à 60 Pa ou moins.
PCT/JP2019/004442 2019-02-07 2019-02-07 Procédé de lyophylisation sous vide et dispositif de séchage par congélation sous vide WO2020161863A1 (fr)

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PCT/JP2019/004442 WO2020161863A1 (fr) 2019-02-07 2019-02-07 Procédé de lyophylisation sous vide et dispositif de séchage par congélation sous vide

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11320200B1 (en) 2021-02-16 2022-05-03 Ulvac, Inc. Freeze-drying device and freeze-drying method
JP7367240B1 (ja) 2022-05-19 2023-10-23 株式会社神鋼環境ソリューション 粒子製造装置および凍結粒子の製造方法

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2006090671A (ja) * 2004-09-27 2006-04-06 Ulvac Japan Ltd 凍結真空乾燥装置および凍結真空乾燥方法
WO2008153039A1 (fr) * 2007-06-14 2008-12-18 Ulvac, Inc. Appareil de lyophilisation sous vide et procédé de lyophilisation sous vide
JP2014520912A (ja) * 2011-06-30 2014-08-25 イー アンド ジェイ ガロ ワイネリイ 天然結晶質着色剤および製造方法
JP2014530685A (ja) * 2011-10-05 2014-11-20 サノフィ パスツール ソシエテ アノニム 凍結乾燥粒子の製造用工程ライン

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2006090671A (ja) * 2004-09-27 2006-04-06 Ulvac Japan Ltd 凍結真空乾燥装置および凍結真空乾燥方法
WO2008153039A1 (fr) * 2007-06-14 2008-12-18 Ulvac, Inc. Appareil de lyophilisation sous vide et procédé de lyophilisation sous vide
JP2014520912A (ja) * 2011-06-30 2014-08-25 イー アンド ジェイ ガロ ワイネリイ 天然結晶質着色剤および製造方法
JP2014530685A (ja) * 2011-10-05 2014-11-20 サノフィ パスツール ソシエテ アノニム 凍結乾燥粒子の製造用工程ライン

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11320200B1 (en) 2021-02-16 2022-05-03 Ulvac, Inc. Freeze-drying device and freeze-drying method
WO2022175999A1 (fr) * 2021-02-16 2022-08-25 株式会社アルバック Appareil et procédé de lyophilisation
US11480390B2 (en) 2021-02-16 2022-10-25 Ulvac, Inc. Freeze-drying device and freeze-drying method
US11732965B2 (en) 2021-02-16 2023-08-22 Ulvac, Inc. Freeze-drying device and freeze-drying method
JP7367240B1 (ja) 2022-05-19 2023-10-23 株式会社神鋼環境ソリューション 粒子製造装置および凍結粒子の製造方法
WO2023224103A1 (fr) * 2022-05-19 2023-11-23 株式会社神鋼環境ソリューション Dispositif de production de particules et procédé de production de particules congelées
JP2023171213A (ja) * 2022-05-19 2023-12-01 株式会社神鋼環境ソリューション 粒子製造装置および凍結粒子の製造方法

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