JP2018048787A - Quick freezing method and quick freezing device for liquid bag - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a rapid freezing method for a liquid bag and a rapid freezing device for uniformly cooling a liquid bag in which a liquid is enclosed without damaging it and freezing the liquid in a short time. A method for rapid freezing of a liquid bag according to the present invention is a method of rapidly freezing a liquid bag having a main body and a tube connecting portion in the main body using a low temperature liquefied gas. A liquid bag mounting step of mounting the liquid bag on a mounting surface, and a liquid-proof wall installation step of providing a liquid-proof wall on the mounting surface so as to surround the mounted liquid bag. A metal plate arranging step of arranging a metal plate so that the metal plate is in contact with the placed body part of the liquid bag and not in contact with the tube connection part, and the body part of the liquid bag in the metal plate And a low-temperature liquefied gas contacting step of bringing the low-temperature liquefied gas into contact with the metal plate by dropping or spraying the low-temperature liquefied gas toward the surface opposite to the surface contacted with is there. [Selection diagram]

Description

  The present invention relates to a quick freezing method and a quick freezing device for a liquid bag for rapidly freezing a liquid bag enclosing a liquid such as a liquid formulation, and more particularly, a liquid bag for rapidly freezing a liquid bag using a low-temperature liquefied gas. The present invention relates to a rapid freezing method and a rapid freezing apparatus.

The liquid preparation is usually sealed in a case for the purpose of preventing contamination with bacteria. As a case for sealing a liquid preparation, a liquid bag made of a 2D (two-dimensional, flat) resin film as shown in FIG. 2 is generally used.
In addition, liquid preparations are generally refrigerated or frozen at a predetermined temperature in order to maintain their effectiveness and safety.

When liquid preparations are stored frozen, it is desired to increase the residual rate of antigen in the liquid preparation. The higher the cooling rate when the liquid preparation is cooled and frozen, the higher the rate of antigen in the liquid preparation. It is known that the survival rate is high.
An example of a specific relationship between the residual rate of the antigen in the liquid preparation and the cooling rate is as follows: In order to make the residual rate of the antigen 90% or more, -50 ° C within 30 minutes from the start of cooling from room temperature, and The target cooling rate is required to be -90 ° C within 50 minutes of cooling from room temperature.

  Patent Document 1 discloses a technique in which a liquid preparation sealed in a sealed container is frozen and then sterilized. In Patent Document 1, a general freezer may be used for freezing, or a cooling refrigerant such as liquid nitrogen may be used.

JP 2014-169250 A

  In order to prolong the storage period of the liquid preparation, it is required to store the liquid preparation in a frozen state. However, the freezing method using a general freezer disclosed in Patent Document 1 satisfies the above target cooling rate. There was a problem that the liquid preparation could not be frozen and the residual ratio of the antigen in the liquid preparation was low.

  Moreover, although the freezing method by spraying liquid nitrogen can freeze the liquid preparation at a sufficient cooling rate, the position where the liquid nitrogen sprayed in the liquid bag is directly touched becomes extremely low temperature, and the liquid made of resin film The bag itself was damaged. Furthermore, since the liquid sealed in the liquid bag expands when frozen, there is a problem that the liquid bag is damaged if the freezing is biased.

  Furthermore, as a method for storing a frozen liquid bag, conventionally, the frozen liquid bag has been placed in the freezer as it is. However, the liquid bag body made of resin film may be damaged or provided in the liquid bag. There is a problem that the tube connecting portion (see FIG. 2) is broken.

  The present invention has been made in order to solve the above-described problems, and when a liquid bag enclosing a liquid such as a liquid preparation is cooled to rapidly freeze the liquid, the liquid bag is damaged. An object of the present invention is to provide a quick freezing method and a quick freezing device for a liquid bag that can freeze the liquid bag in a short time.

(1) The liquid bag rapid freezing method according to the present invention is a liquid bag rapid freezing that rapidly freezes a main body and a liquid bag provided with a tube connection portion on the main body using a low-temperature liquefied gas. A liquid bag placing step for placing the liquid bag on a placement surface; and a liquid barrier provided on the placement surface so as to surround the periphery of the placed liquid bag. A liquid wall placement step, a metal plate placement step for placing the metal plate in contact with the body portion of the placed liquid bag and not in contact with the tube connection portion, and the liquid in the metal plate A low-temperature liquefied gas contact step of dropping or spraying the low-temperature liquefied gas toward the surface opposite to the surface in contact with the main body of the bag for contacting the low-temperature liquefied gas with the metal plate. It is a feature.

(2) In the above (1), the low-temperature liquefied gas contact step is based on a temperature measurement step of measuring the temperature of the contact surface between the metal plate and the liquid bag, and the measured temperature. And a low-temperature liquefied gas amount adjusting step for adjusting a dripping or spraying amount of the low-temperature liquefied gas.

(3) In the above (1) or (2), the metal plate is made of aluminum or an aluminum alloy.

(4) A quick freeze apparatus for a liquid bag according to the present invention rapidly freezes a main body part and a liquid bag provided with a tube connecting part on the main body part using a low-temperature liquefied gas. Metal disposed so as to contact the liquid barrier provided on the mounting surface so as to surround the liquid bag mounted on the mounting surface and the main body of the liquid bag mounted A low-temperature liquefied gas nozzle that drops or sprays the low-temperature liquefied gas toward a surface opposite to a surface of the metal plate that is in contact with the main body of the liquid bag. Is.

(5) In the above (4), the temperature measuring device for measuring the temperature of the contact surface between the metal plate and the main body of the liquid bag, and the dripping or spraying amount of the low-temperature liquefied gas nozzle. An adjustment valve for adjustment and a control unit for adjusting the opening of the adjustment valve based on a measurement value of the temperature measuring device are provided.

(6) In the above (4) or (5), the metal plate is made of aluminum or an aluminum alloy.

  The rapid freezing method for a liquid bag according to the present invention is a rapid freezing method for a liquid bag in which a main body portion and a liquid bag provided with a tube connection portion are rapidly frozen using a low-temperature liquefied gas. A liquid bag placement step for placing the liquid bag on a placement surface, and a liquid barrier placement step for providing a liquid barrier wall on the placement surface so as to surround the liquid bag placed on the placement surface. And a metal plate arranging step for placing the metal plate in contact with the main body portion of the placed liquid bag and not in contact with the tube connecting portion, and the main body of the liquid bag in the metal plate And a low-temperature liquefied gas contact step of bringing the low-temperature liquefied gas into contact with the metal plate by dropping or spraying the low-temperature liquefied gas toward the surface opposite to the surface in contact with the section, for the liquid Uniform only on the body of the bag By telling the cold can be a short time rapidly freezing the liquid sealed in the liquid bag without damaging the main body portion and the tube connecting portion of the liquid bag.

It is explanatory drawing explaining the quick freezing method and quick freezing apparatus of the bag for liquids concerning embodiment of this invention. It is explanatory drawing explaining the bag for liquid which enclosed the liquid to be rapidly frozen in this invention.

  A liquid bag quick freezing device 1 (hereinafter simply referred to as “rapid freezing device 1”) according to an embodiment of the present invention includes, as shown in FIG. The liquid bag 21 provided with 25 is rapidly frozen using a low-temperature liquefied gas, and includes a liquid barrier 3, a metal plate 5, a dripping nozzle 7, a temperature measuring device 9, and a regulating valve 11. And a control unit 13. Hereinafter, after describing the liquid bag 21, each component of the quick freezing apparatus 1 will be described in detail.

  In the drawings used in the following description, in order to make the characteristics of the configuration according to the embodiment of the present invention easier to understand, the characteristic part may be shown in an enlarged manner for convenience. The size, thickness, dimensions, etc. are not necessarily the same as the actual dimensional ratios.

<Bag for liquid>
As shown in FIG. 2, the liquid bag 21 according to the present invention has a 2D (two-dimensional, flat) shape, and a tube 27 is connected to the tube connecting portion 25. The liquid bag 21 is made of a resin film.
The liquid bag 21 encloses a liquid preparation as an object to be frozen. However, the liquid bag 21 is not limited to a liquid preparation as an object to be enclosed in the liquid bag 21 as an object to be frozen.

<Liquid barrier>
The liquid barrier 3 is provided on the placement surface 15 so as to surround the periphery of the liquid bag 21 placed on the placement surface 15, and the low-temperature liquefied gas dropped from the dropping nozzle 7 described later is provided. This prevents the liquid from flowing directly through the mounting surface 15 to the liquid bag 21.
In addition, the mounting surface 15 of the present embodiment is made of stainless steel.

<Metal plate>
The metal plate 5 is disposed so as to come into contact with the main body portion 23 of the liquid bag 21 placed on the placement surface 15, and as shown in FIG. The connection part 25 and the tube 27 are not in contact, but are in contact with the main body part 23.
In the present embodiment, an aluminum plate having a thickness of 2 mm is used as the metal plate 5. However, the present invention is not limited to this, and a material having strength, withstanding low temperatures and good thermal conductivity (for example, Aluminum alloy).

<Drip nozzle>
The dripping nozzles 7 are provided as a plurality of low-temperature liquefied gas nozzles that contact the low-temperature liquefied gas toward the upper surface 5b opposite to the lower surface 5a of the metal plate 5 that is in contact with the main body 23 of the liquid bag 21. Yes, as shown in FIG. 1, a plurality of liquid nitrogen is dropped over the metal plate 5.
In the portion (A and B in FIG. 1) where liquid nitrogen is dropped by the liquefying nozzle 7 on the upper surface 5b of the metal plate 5 and the placement surface 15, the liquid nitrogen evaporates to generate cold heat.

<Temperature measuring device>
The temperature measuring device 9 measures the surface temperature of the liquid bag 21 at the contact surface between the metal plate 5 and the main body 23 of the liquid bag 21.
In the present embodiment, a thermocouple is used as the temperature measuring device 9, but the present invention is not limited to this, and any device capable of measuring from room temperature to extremely low temperature may be used.

<Regulating valve>
The regulating valve 11 is provided in a pipe 17 that supplies liquid nitrogen to the dropping nozzle 7, and controls the amount of liquid nitrogen dripped from the dropping nozzle 7.
In the present embodiment, a control valve is used as the adjustment valve 11, but the present invention is not limited to this, and any valve that can adjust the opening degree may be used.

<Control unit>
The controller 13 adjusts the opening degree of the regulating valve 11, and is electrically connected to the temperature measuring device 9 and the regulating valve 11 as shown in FIG. 1, and is a liquid bag measured by the temperature measuring device 9. The temperature of 21 is acquired at predetermined time intervals, and the opening degree of the adjusting valve 11 is adjusted based on the acquired temperature.
For example, a temperature controller can be used as the control unit 13, but is not limited to this, and any controller that adjusts the opening of the adjustment valve 11 based on the acquired temperature of the temperature measuring device 9 can be used. good.

  Next, a method for rapidly freezing a liquid bag according to an embodiment of the present invention will be described with reference to FIGS.

In the liquid bag rapid freezing method according to the present embodiment, the liquid bag 21 (see FIG. 2) in which the tube connecting portion 25 is provided in the main body portion 23 and the main body portion 23 is used as liquid cryogenic gas. Quick-freezing, equipped with a liquid bag placement step, a liquid barrier installation step, a metal plate placement step, a low-temperature liquefied gas contact step, a temperature measurement step, and a low-temperature liquefied gas amount adjustment step For example, the quick freezing apparatus 1 shown in FIG. 1 can be used.
Hereafter, each said process is demonstrated in detail.

<Liquid bag placement process>
The liquid bag placement step is a step of placing the liquid bag 21 on the placement surface 15. At this time, since the mounting surface 15 is a stainless steel plate and has a high thermal conductivity, they do not contact the mounting surface 15 in order to prevent damage to the tube connecting portion 25 and the tube 27 as shown in FIG. Like that.

<Liquid barrier installation process>
As shown in FIG. 1, the liquid-proof wall installation step is a step of installing the liquid-proof wall 3 on the placement surface 15 so as to surround the periphery of the liquid bag 21 placed on the placement surface 15.

<Metal plate placement process>
As shown in FIG. 1, the metal plate placement step is a step of placing the metal plate 5 in contact with the main body 23 of the liquid bag 21 placed on the placement surface 15, as shown in FIG. 1. The upper surface 5b of the main body 23 and the lower surface 5a of the metal plate 5 are brought into contact with each other.
Further, in the metal plate arranging step, the metal plate 5 is arranged by providing a space so that the tube connecting portion 25 and the tube 27 do not come into contact with the lower surface 5 a of the metal plate 5 as in the liquid bag placing step described above.

<Low temperature liquefied gas contact process>
In the low-temperature liquefied gas contact step, liquid nitrogen is dropped as a low-temperature liquefied gas toward the upper surface 5b opposite to the lower surface 5a of the metal plate 5 that is in contact with the main body 23 of the liquid bag 21, and is brought into contact with the metal plate 5. It is a process.

<Temperature measurement process>
The temperature measurement step is a step of measuring the surface temperature of the liquid bag 21 that is a contact surface with the lower surface 5a of the metal plate 5, and is installed between the metal plate 5 and the liquid bag 21 in FIG. The temperature is measured by the temperature measuring device 9.

<Low-temperature liquefied gas amount adjustment process>
The low-temperature liquefied gas amount adjusting step is a step of acquiring the surface temperature of the liquid bag 21 measured in the temperature measuring step and adjusting the amount of liquid nitrogen dropped from the dropping nozzle 7 based on the acquired temperature. As shown in FIG. 1, the opening degree of the regulating valve 11 can be adjusted based on the measured value of the temperature measuring device 9 using the control unit 13 in which the temperature measuring device 9 and the regulating valve 11 are electrically connected. .

  When a low temperature liquefied gas such as liquid nitrogen is sprayed directly on the liquid bag, the position where the low temperature liquefied gas is directly touched becomes extremely low temperature locally, and the resin film liquid bag itself may be damaged, or the liquid bag There is a problem that the liquid bag encapsulated inside is partially frozen or the liquid bag is locally expanded and damaged, but the liquid bag according to the present embodiment is rapidly frozen. According to the apparatus and the quick freezing apparatus method, the liquid nitrogen dripped or sprayed on the upper surface of the metal plate evaporates to generate cold heat, and the generated cold heat spreads instantly and evenly on the metal plate, thereby liquefying at low temperature. The liquid bag can be cooled in a planar and uniform manner without directing gas to the liquid bag, and the liquid enclosed in the liquid bag can be rapidly and quickly removed without damaging the liquid bag. It can be sintering.

  In the above description, liquid nitrogen is dropped as the low-temperature liquefied gas, but a plurality of spray nozzles may be used instead of the dropping nozzle. Thereby, compared with the case where a low temperature liquefied gas is dripped, since liquid nitrogen can be made to contact a metal plate more uniformly and it can cool more uniformly, it is preferable.

  As described above, when a liquid preparation is enclosed in a liquid bag and stored frozen, it may be necessary to reduce the temperature of the liquid bag according to a predetermined cooling rate. Therefore, it is required to accurately control the amount of liquid nitrogen based on the surface temperature of the liquid bag measured by the above.

  Therefore, in order to strictly control the cooling rate of the liquid bag, for example, the low-temperature liquefied gas nozzle is a plurality of spray nozzles that spray liquid nitrogen toward the upper surface of the metal plate, and the amount of liquid nitrogen to be sprayed If the controller that controls the temperature of the liquid bag measured by the temperature measuring device acquires every 0.1 s and the opening degree of the regulating valve can be sequentially adjusted based on the acquired surface temperature good.

  In this embodiment, a stainless steel plate is used for the mounting surface, but the present invention is not limited to this, and any material that has strength and can withstand low temperatures can be used. When the surface is made of a material having good thermal conductivity such as metal, the liquid nitrogen evaporates at the portion (B in FIG. 1) where the liquid nitrogen is sprayed or dropped on the mounting surface, and cold heat is generated. The main body of the liquid bag in contact with the surface can be cooled evenly in a flat manner.

  In addition, the liquid barrier provided so as to surround the liquid bag can set the height so as to be in contact with the metal plate, so that cold heat can be transmitted between the metal plate and the mounting surface. The body portion of the bag can be cooled more efficiently from the upper and lower surfaces.

  Furthermore, by providing a side wall on the upper surface of the metal plate (the surface on which the low-temperature liquefied gas is dropped or sprayed), liquid nitrogen dropped or sprayed on the metal plate is prevented from spilling from the metal plate, and the consumption of liquid nitrogen is reduced. Can be reduced.

  Note that the above description has been made so that the tube connection part and the tube of the liquid bag, which are easily damaged by quick freezing, and the tube do not contact the lower surface and the mounting surface of the metal plate. Although a space was provided between the surface and the surface of the metal plate, a structure with low thermal conductivity (for example, resin) pasted on the lower surface or mounting surface of the metal plate, the tube connection part or the tube was heated. It may be wrapped in a material with low conductivity.

  In addition, the above description uses a temperature measuring device, a regulating valve, and a control unit, but these are provided for the purpose of suppressing the consumption of liquid nitrogen and controlling the cooling rate of the liquid bag. Thus, the present invention includes a device for rapidly freezing a liquid bag without installing a temperature measuring device, a regulating valve, and a control unit.

  A specific experiment for confirming the effect of the quick freezing method and the quick freezing apparatus for the liquid bag according to the present invention was conducted, and the results will be described below.

  In the experiment, the liquid enclosed in the liquid bag 21 is frozen using the quick freezing apparatus 1 shown in FIG.

In the experiment, a 2D (two-dimensional, flat) medical bag (manufactured by Pall Co., Ltd., capacity: 3 L, material: LDPE + PE + EVOH laminated structure) was used as the liquid bag 21.
As a liquid preparation to be frozen by being enclosed in the liquid bag 21, 2.5 L of vaccine simulation liquid was used. Further, a tube 27 (material: PE) was connected to the tube connecting portion 25 of the liquid bag 21.

In this embodiment, as an example of the invention, the liquid bag 21 was rapidly frozen using the quick freezing apparatus 1 shown in FIG.
First, the liquid bag 21 is placed on the placement surface 15 (liquid preparation bag placement step), and the liquid-proof wall 3 is provided on the placement surface 15 so as to surround the placed liquid bag 21. (Liquid barrier installation process).

  Next, the metal plate 5 was arrange | positioned so that the lower surface 5a might contact the main-body part 23 of the mounted bag 21 for liquids (metal plate arrangement | positioning process). At this time, the temperature measuring device 9 was installed between the metal plate 5 and the liquid bag 21.

  And liquefied nitrogen was sprayed toward the upper surface 5b of the metal plate 5 (low temperature liquefied gas contact process). Here, the temperature of the contact surface between the metal plate 5 and the liquid bag 21 was measured (temperature measurement step), and the spray amount of liquid nitrogen was adjusted based on the measured temperature (low temperature liquefied gas amount adjustment step).

  In the invention example, the cooling rate for cooling the liquid bag 21 is such that the time required from normal temperature to -50 ° C is 25 minutes and the time required from normal temperature to -90 ° C is 45 minutes. Controlled. At this time, the temperature was acquired every 0.1 s in the temperature measurement step, and the spray amount of liquid nitrogen was adjusted based on the temperature acquired every 0.1 s in the low temperature liquefied gas amount adjustment step.

  In this embodiment, as a comparative example, the liquid bag 21 is directly stored in a freezer of a liquid nitrogen type freezer that has been cooled to a preset temperature (−120 °) in advance, and the liquid preparation in the liquid bag 21 is frozen. It was. In the comparative example, the same material as that of the above-described invention example was used for the material of the liquid bag 21, the liquid preparation sealed in the liquid bag 21, and the tube 27. The liquid nitrogen type freezer was always sprayed with liquid nitrogen so that the inside of the freezer was constant at a set temperature of -120 ° C. At this time, liquid nitrogen was not sprayed directly onto the liquid bag 21 and the tube 27.

  In both the inventive example and the comparative example, the time required for cooling the liquid bag 21 to a predetermined temperature (−50 ° C. and −90 ° C.) is measured, and the liquid bag 21 and the tube 27 in which the liquid is frozen are measured. The damage situation of was observed.

The results in this example were as follows.
First, in the inventive example, the liquid sealed in the liquid bag 21 could be frozen without causing damage to the liquid bag 21 and the tube 27.
The time required for cooling from the specified room temperature (+ 5 ° C) to -50 ° C is 25 minutes, and the time required from room temperature to -90 ° C is 45 minutes. 21 was cooled and the liquid formulation could be quickly frozen.

  On the other hand, in the comparative example, liquid nitrogen was not sprayed directly onto the liquid bag 21 and the tube 27, so that the liquid sealed in the liquid bag 21 was frozen without causing damage to the liquid bag 21 and the tube 27. I was able to. However, the time required to cool from normal temperature (+ 5 ° C) to -50 ° C is 66 minutes, and the time required from normal temperature to -90 ° C is 81 minutes. The liquid preparation enclosed in the liquid bag 21 could not be rapidly frozen.

  As described above, according to the rapid freezing method and apparatus according to the present invention, it has been demonstrated that the liquid enclosed in the liquid bag can be rapidly frozen without damaging the liquid bag.

DESCRIPTION OF SYMBOLS 1 Quick freeze apparatus 3 Liquid barrier 5 Metal plate 5a Lower surface 5b Upper surface 7 Dripping nozzle 9 Temperature measuring device 11 Control valve 13 Control part 15 Mounting surface 17 Piping 21 Liquid bag 23 Main body part 25 Tube connection part 27 Tube

Claims (6)

A liquid bag quick freezing method in which a main body part and a liquid bag provided with a tube connection part on the main body part are rapidly frozen using a low-temperature liquefied gas,
A liquid bag placement step of placing the liquid bag on a placement surface;
A liquid-proof wall installation step of providing a liquid-proof wall on the mounting surface so as to surround the periphery of the placed liquid bag;
A metal plate placement step of placing the metal plate in contact with the body portion of the placed liquid bag and not in contact with the tube connection portion;
A low-temperature liquefied gas contact process in which the low-temperature liquefied gas is dropped or sprayed toward the surface opposite to the surface of the metal plate that is in contact with the main body of the liquid bag to bring the low-temperature liquefied gas into contact with the metal plate. A quick freezing method for a liquid bag.   The low-temperature liquefied gas contact step includes a temperature measurement step for measuring the temperature of the contact surface between the metal plate and the liquid bag, and a low temperature for adjusting the dripping or spraying amount of the low-temperature liquefied gas based on the measured temperature. A method for rapidly freezing a liquid bag according to claim 1, further comprising a liquefied gas amount adjusting step.   The method for rapidly freezing a liquid bag according to claim 1 or 2, wherein the metal plate is made of aluminum or an aluminum alloy. A liquid bag quick freezing device for rapidly freezing a main body part and a liquid bag provided with a tube connection part on the main body part using a low-temperature liquefied gas,
A liquid barrier provided on the placement surface so as to surround the periphery of the liquid bag placed on the placement surface;
A metal plate disposed so as to contact the main body of the liquid bag placed thereon;
A liquid bag comprising: a low-temperature liquefied gas nozzle for dropping or spraying the low-temperature liquefied gas toward a surface opposite to the surface of the metal plate in contact with the main body of the liquid bag. Quick freezing equipment. A temperature measuring device for measuring the temperature of the contact surface between the metal plate and the main body of the liquid bag;
An adjustment valve for adjusting the amount of dripping or spraying of the low-temperature liquefied gas nozzle;
The liquid bag rapid freezing apparatus according to claim 4, further comprising a control unit that adjusts an opening of the adjusting valve based on a measurement value of the temperature measuring device.   6. The quick freezing device for a liquid bag according to claim 4, wherein the metal plate is made of aluminum or an aluminum alloy.