Patent Publication Number: US-11644236-B2

Title: Vacuum freeze-drying apparatus and vacuum freeze-drying method

Description:
TECHNOLOGY FIELD 
     The present invention relates to a vacuum freeze-drying apparatus and a vacuum freeze-drying method. 
     BACKGROUND TECHNOLOGY 
     Conventionally, a freeze-drying apparatus has been proposed in which droplets are produced, and the frozen particles freeze-solidified with the droplets are freeze-dried (Patent Document 1). 
     In addition, a freeze-drying apparatus has also been proposed in which a shelf for receiving frozen materials is tilted (Patent Document 2). 
     Further, a vacuum freeze-drying apparatus has been proposed in which frozen particles are sublimated and dried by the kinetic energy obtained at the time of spraying (Patent Document 3). 
     PRIOR ART DOCUMENTS 
     Patent Documents 
     
         
         Patent Document 1 International Opening WO2013/050162 
         Patent Document 2 International Opening WO2010/005021 
         Patent Document 3 International Opening WO2019/235036 
       
    
     SUMMARY OF THE INVENTION 
     Problem to be Solved by the Invention 
     However, in the above documents, there is a problem that vacuum freeze-drying cannot be continuously performed in a short time. 
     Therefore, the present invention has been made in view of the above problems and provides a vacuum freeze-drying apparatus and a vacuum freeze-drying method capable of continuously performing vacuum freeze-drying in a short time. 
     Solution to the Problem 
     In order to solve the above problems, (1) the present invention provides a vacuum freeze-drying apparatus comprising a vacuum freezing device for freezing a liquid, and a drying device for sublimating and drying a frozen substance frozen as above. The vacuum freeze-drying apparatus comprises an exhaust path for performing vacuum suction, and the drying device comprises a tubular member formed of a tubular shape provided with an inlet portion and an outlet portion, a temperature adjusting means provided in a plurality of regions formed toward a direction from the inlet portion to the outlet portion of a peripheral portion of the tubular member, wherein the plurality of regions are at least three or more regions whose temperature is capable of being controlled, and the temperature adjusting means adjusts a temperature of the plurality of regions in an outer surface of the tubular member, a temperature control unit for independently controlling the temperature adjusting means, and a rotating portion for rotating the tubular member. The tubular member has a spiral transfer means continuously provided adjacent to an inner wall of the tubular member toward a direction from the inlet portion to the outlet portion, and the transfer means transfers the frozen substance entering from the inlet portion sequentially to locations corresponding to the plurality of regions in the tubular member by the transfer means to continuously sublimate and dry the frozen substance. 
     (2) In the configuration of the above (1), the plurality of regions of the three or more regions comprise at least a temperature region of a minus temperature, a temperature region in a range from the minus temperature to plus 40° C., and a temperature region of 20° C. or higher, provided toward a direction from the inlet portion to the outlet portion respectively. 
     (3) In the configuration of the above (1) or (2), a substance produced therefrom is an injectable substance or a drug in solid formulation, and a periphery of a tubular member is covered with clean air. 
     (4) In the configuration of the above (1) to (3), the rotating portion comprises a rotational drive transmitting portion for transmitting rotational drive provided in one or a plurality of locations in an axial direction, and a rotation support portion configured by a rotary roller and/or a bearing for supporting rotation by the rotational drive transmitting portion. 
     (5) In the configuration of the above (1) to (4), the rotating portion has a rotation speed of 1/30 rpm or more and 1 rpm or less. 
     (6) In the configuration of the above (1) to (5), the transfer means is formed by providing a spiral wall portion in an inner wall of the tubular member. 
     (7) In the configuration of the above (1) to (5), the transfer means is configured by a groove portion formed in an inner wall of the tubular member, and the depth of the groove portion is 3 mm or more and 50 mm or less. 
     (8) In the configuration of the above (1) to (7), the tubular member includes a contact type or non-contact type temperature detection unit, and the temperature control unit controls a temperature of the temperature adjusting means according to a surface temperature of the tubular member or a temperature of a substance in the tubular member detected by the temperature detection unit. 
     (9) In the configuration of the above (1) to (8), a moisture detection unit is provided outside the tubular member for detecting a moisture content of a substance in the tubular member through a transparent glass or resin window portion, and the temperature control unit controls a temperature of the temperature adjusting means according to the moisture content of a substance in the tubular member detected by the moisture detection unit. 
     (10) In the configuration of the above (1) to (9), the tubular member is made of stainless steel. 
     (11) The present invention provides a vacuum freeze-drying method comprising a vacuum freezing step for freezing a liquid, a drying step for sublimating and drying a frozen substance frozen as above, and a step for performing vacuum suction through an exhaust path. The drying step comprises a step for rotating a tubular member formed of a tubular shape having an inlet portion and an outlet portion, wherein the tubular member has a spiral transfer means continuously provided adjacent to an inner wall of the tubular member toward a direction from the inlet portion to the outlet portion, a step for adjusting temperatures of a plurality of regions provided toward a direction from the inlet portion to the outlet portion in a peripheral portion of the tubular member, wherein the plurality of regions are at least three or more regions whose temperature is capable of being controlled, and a step for continuously sublimating and drying the frozen substance entering from the inlet portion while the frozen substance is transferred sequentially to locations corresponding to the plurality of regions in the tubular member. 
     (12) In the configuration of the above (1) to (10), The connecting portion is configured that by a rotation of screw arranged in a transfer pipe having one end facing the collecting portion of the vacuum freezing device and the other end facing the inside of the tubular portion, the frozen material entering from the collecting portion is moved in the axial direction of the screw. 
     (13) In the configuration of the above (12), a base end portion of the screw on the vacuum freezing device side is bearing by a bearing portion, a first suction port is provided in the vicinity of the bearing portion, and it is configured that the inside of the transfer pipe is constantly maintained in a vacuum through the first suction port. A tip portion of the transfer pipe on the drying device side is configured as a bearing portion to rotationally support an end member of the tubular portion of the tubular member of the drying device, a second suction port is provided between the end member and the bearing portion on the tip end side of the transfer pipe, and it is configured that the inside of the transfer pipe and the inside of the tubular portion are maintained in a vacuum through the second suction port. 
     (14) In the configuration of the above (12) or (13), the screw is a spiral coil structure located around a rotation axis, and provided in a state close to the inner wall of the transfer pipe. It is configured to send the frozen material received from the collecting portion to the tubular portion by a rotation of the screw. 
     (15) In the configuration of the above (12) to (14), the screw is rotationally driven by a rotational driving means different from the rotating portion for rotating the tubular portion. 
     Effect of the Invention 
     According to the present invention, it enables to provide a vacuum freeze-drying apparatus and a vacuum freeze-drying method capable of continuously performing vacuum freeze-drying in a short time. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG.  1    is an explanatory diagram of a vacuum freeze-drying apparatus according to an embodiment to the present invention. 
         FIG.  2    shows a cross-sectional view of a drying device, a connection portion, and a collection portion in a vacuum freeze-drying apparatus of  FIG.  1   . 
         FIG.  3    is a front view of a drying device of a vacuum freeze-drying apparatus according to an embodiment to the present invention. 
         FIG.  4    is a plan view of a drying device of a vacuum freeze-drying apparatus according to an embodiment to the present invention. 
         FIG.  5 A  is a left side view of a drying device and  FIG.  5 B  is a right side view of a drying device. 
         FIG.  6    is a cross-sectional view in a line from A to A of  FIG.  1   . 
         FIGS.  7 A to  7 E  show a tubular portion  31 B among a plurality of tubular portions  31 A to  31 F constituting a tubular member  31 . 
         FIG.  8    shows a half body  31 BX of a tubular portion  31 B. 
         FIG.  9    shows how a detection unit detects a temperature of substance or the amount of moisture of a substance inside. 
         FIG.  10    is a cross-sectional view of a connection portion of a vacuum freeze-drying apparatus according to an embodiment. 
         FIG.  11    is a diagram showing another example of a half body  31 BX of a tubular portion  31 B in  FIGS.  7 A to  7 E . 
         FIG.  12    is a cross-sectional view of a connection portion of a vacuum freeze-drying apparatus according to another example of an embodiment of the present invention. 
     
    
    
     EMBODIMENTS TO CARRY OUT THE INVENTION 
     Next, a vacuum freeze-drying apparatus according to an embodiment to the present invention will be described. Further, the same member or a member having the same function may be designated by the same reference numeral, and the description may be omitted as appropriate after the member is described. 
       FIG.  1    is an explanatory diagram of a vacuum freeze-drying apparatus according to an embodiment to the present invention.  FIG.  2    shows a cross-sectional view of a drying device, a connection portion, and a collection portion in a vacuum freeze-drying apparatus of  FIG.  1   . 
     As shown in  FIG.  1   , a vacuum freeze-drying apparatus  1  has a vacuum freezing device  2 , a drying device  3 , a connection portion  4 , and a collection portion  5 . 
     Substance handled by a vacuum freeze-drying apparatus  1  is an injectable substance or a drug in solid formulation. 
     A vacuum freezing device  2 , for example, sprays a raw material solution containing a raw material into a vacuum container from a spray nozzle  21  to produce a frozen substance by freezing a sprayed raw material solution. Further, a vacuum freezing device may be one in which a raw material solution is dropped from a nozzle into a vacuum container, so it is enable to produce a frozen substance by freezing dropped droplets. A sprayed or dropped raw material solution self-freezes due to an evaporation of water during the fall and the deprivation of latent heat of vaporization, resulting in a frozen substance which is a fine frozen particle. A frozen substance falls toward a collecting portion  22  having a tapered shape with a smaller opening, and is collected by the collecting portion  22 . 
     A connection portion  4  connects a vacuum freezing device  2  and a drying device  3  for transporting a frozen substance produced at a vacuum freezing device  2  to a drying device  3 . 
     A drying device  3  is to continuously sublimate and dry a frozen substance. A collection portion  5  collects a dried material formed by sublimating and drying at a drying device  3  since it is be evolved from an outlet portion  31   c  of a tubular member  31 . 
     A vacuum freeze-drying apparatus  1  has an exhaust path for performing vacuum suction, wherein the exhaust path is provided in a connection portion  4  according to an embodiment. The exhaust path may be provided in a vacuum freezing device  2 , a drying device  3 , or a connection portion  4 . By providing an exhaust path, it enables to maintain reduced-pressure atmosphere inside, to make a circumstance where liquid is difficult to be present and solid or gas is present. 
     A tubular member  31  and a collection portion  5  are covered by clean air  6  in the periphery. Any surrounding outer surface portion of a decomposable connecting portion of a tubular member  3  is all covered by clean air  6  so that it is configured to allow clean air to enter against a leak. 
       FIG.  3    is a front view of a drying device of a vacuum freeze-drying apparatus related to an embodiment of the present invention.  FIG.  4    is a plan view of a drying device of a vacuum freeze-drying apparatus according to an embodiment of the present invention.  FIG.  5 A  is a left side view of a drying device and  FIG.  5 B  is a right side view of a drying device.  FIG.  6    is a cross-sectional view of a line from A to A in  FIG.  1   . 
     As shown in  FIGS.  1  to  6   , a drying device  3  is provided with a tubular member  31 , a temperature adjusting means  30   a  to  30   j , a rotating portion  7 , and a temperature control unit  8 . 
     A tubular member  31  is formed of a tubular shape extending in a linear manner in a horizontal direction, having an opening, provided with an inlet portion  31   b  for letting a frozen substance enter into, and an outlet portion  31   c  for being an outlet for a dried material sublimated and dried (See  FIG.  2   ). 
     In a tubular member  31 , provided is a spiral transfer means  31   a  continuously provided adjacent to an inner wall of a tubular member  31  from an inlet portion  31   b  toward an outlet portion  31   c . A frozen substance transported from a connection portion  4  enters from an inlet portion  31   b  of a tubular member  31  and is transferred to an outlet portion  31   c  by a spiral transfer means  31   a , during which a frozen substance is continuously sublimated and dried. 
     Temperature adjusting means  30   a  to  30   j  are provided in an outer peripheral portion of a tubular member  31  and adjust temperatures of a plurality of regions  40   a  to  40   j  in an outer surface of a tubular member  31 . 
     A plurality of regions  40   a  to  40   j  are provided from an inlet portion  31   b  toward an outlet portion  31   c  of a tubular member  31 , and temperatures thereof can be independently controlled. Temperature adjusting means  30   a  to  30   j  adjust temperatures of locations in a tubular member  31  corresponding to a plurality of regions  40   a  to  40   j  by adjusting temperatures in a plurality of regions  40   a  to  40   j.    
     Here, ten temperature adjusting means  30   a  to  30   j  are provided, so a plurality of regions formed by a temperature adjusting means  30   a  to  30   j  are provided ten. It is preferred that a plurality of regions  40   a  to  40   j  have at least 3 or more regions. It is noted that a plurality of a temperature adjusting means may be described collectively as a temperature adjusting means, or each temperature adjusting means may be described as a temperature adjusting means respectively. 
     A rotating portion  7  is for rotating a tubular member  31  at the center of a pivot. As a tubular member  31  is rotated by a rotating portion  7 , a frozen substance entering from an inlet portion  31   b  of a tubular member  31  is sequentially transferred through a spiral transfer means  31   a  toward an outlet portion  31   c  in a tubular member  31 . During the course, a frozen substance is continuously sublimated and dried. A rotating portion  7  is configured to rotate only a tubular member  31  and not to rotate temperature adjusting means  30   a  to  30   j  outside a tubular member  31 . Temperature adjusting means  30   a  to  30   j  are fixed not to rotate. 
     A temperature control unit  8  has functions of inputting and outputting information, and independently controls temperature adjusting means  30   a  to  30   j  for adjusting temperatures of a plurality of regions  40   a  to  40   j  formed in an outer surface of a tubular member  31 . 
     Next, temperature adjusting means  30   a  to  30   j  will be described. 
     As shown in  FIG.  1    and  FIG.  2   , temperature adjusting means  30   a  to  30   j  can respectively and independently adjust a temperature of outer space around a tubular member  31  and adjust a temperature of each space in a tubular member  31  respectively. 
     A temperature adjusting means  30   a  adjusts a temperature of a space of a region  40   a  and adjusts a temperature of a space in a tubular member  31  corresponding to a region  40   a . In addition, a temperature adjusting means  30   b  adjusts a temperature of a space of a region  40   b  and adjusts a temperature of a space in a tubular member  31  corresponding to a region  40   b . A temperature adjusting means  30   c  adjusts a temperature of a space of a region  40   c  and adjusts a temperature of a space in a tubular member  31  corresponding to a region  40   c . Similarly, temperature adjusting means  30   d  to  30   j  adjust temperatures of spaces of regions  40   d  to  40   j  and adjust temperatures of spaces in a tubular member  31  corresponding to regions  40   d  to  40   j.    
     A frozen substance entering from an inlet portion  31   b  of a tubular member  31  is continuously sublimated and dried by advancing through spaces where each temperature is adjusted by temperature adjusting means  30   a  to  30   j  respectively. 
     Next, an example of temperature adjusting means  30   a  to  30   j  will be specifically described with reference to  FIGS.  3  to  6   . Although a temperature adjusting means  30   b  will be described as an example, other temperature adjust means may be configured in a similar manner. A temperature adjusting means  30   b  comprises a wall portion  32  on the side of an inlet portion  31   b  of a tubular member  31 , a wall portion  33  on the side of an outlet portion  31   c , a cover  34  for covering a space surrounded by the wall portions  32  and  33  to surround a tubular member  31 , and ducts  35   a  and  35   b  for supplying gas to a wall portion  32  or  33  respectively. Wall portions  32  and  33  are both in a circular shape. A cover  34  is formed by a material such as a transparent resin so that it can visualize an interior, and is for covering a space surrounded by a wall portion  32  and a wall portion  33 . A wall portion  32  and a wall portion  33  are connected to ducts  35   a  and  35   b  so that ducts  35   a  and  35   b  can supply gas. Temperatures in a plurality of regions  40   a  to  40   j  is adjusted to each target temperature by gas so supplied. 
     An air blowing means (not shown) is connected to ducts  35   a  and  35   b , and a temperature-controlled gas is supplied. By supplying gas from ducts  35   a  and  35   b  into regions  40   a  to  40   j  covered by a wall portion  32 , a wall portion  33  and a cover  34 , temperatures in a plurality of regions  40   a  to  40   j  are independently controlled. For example, air can be supplied as gas, but it is not limited to air. 
     Although gas is used as an example to describe temperature adjusting means  30   a  to  30   j , but not limited to gas, an electrical heater, refrigerant, etc. can be used. 
     The inside of wall portions  32 ,  33  has a circular opening matching an outer shape of a tubular member  31 . The inside openings of wall portions  32 ,  33  are preferably close to an outer periphery of a tubular member  31 . 
     Next, temperatures of a plurality of regions  40   a  to  40   j  are described. 
     A plurality of regions  40   a  to  40   j  has at least three or more regions from an inlet portion  31   b  toward an outlet portion  31   c  of a tubular member  31 , these three or more regions include the following (1) to (3) temperature regions. A temperature region is defined by measuring a temperature of a tubular member  31  which is itself a tube at the time when the process gets to a stable operation state, in a manner of a contact type and/or a non-contact type to an outer surface of a tubular member  31 . 
     Included are at least (1) a minus temperature region, (2) a temperature region in a range from the minus temperature to plus 40° C., and (3) a temperature region of plus 20° C. or higher. 
     A minus temperature region of (1) refers to a minus temperature region, such as −40° C., −30° C., −20° C., etc. 
     A temperature region (2) in a range from the minus temperature of (1) to plus 40° C. refers to a temperature region in a range from a minus temperature of the minus temperature region (1) to plus 40° C. For example, when a temperature of the minus temperature region of (1) is −40° C., since this −40° C. plus 40° C., a temperature region of (2) becomes a temperature region in a range from −40° C. to 0° C. Also, when a temperature of a minus temperature region of (1) is −20° C., since this −20° C. plus 40° C., a temperature region of (2) becomes a temperature region in a range from −20° C. to 20° C. 
     A temperature region of plus 20° C. or higher of (3) refers to a temperature region of 0° C.+20° C. or higher, when an upper limit temperature of (2) is 0° C. 
     From an inlet portion  31   b  toward an outlet portion  31   c  of a tubular member  31 , a plurality of regions  40   a  to  40   j  include at least three regions of the above (1) to (3), a frozen substance or a dry substance is transferred by a transfer means  31   a  sequentially to locations in a tubular member  31  corresponding to a plurality of regions  40   a  to  40   j  including those (1) to (3) temperature regions, and a frozen substance or a dry substance is continuously sublimated and dried. 
     Next, a tubular member  31  is described. 
     A tubular member  31  is preferably made of stainless steel. A length of a tubular member  31  is preferably for example a range from 100 mm to 2000 mm, more preferably a range from 150 mm to 1000 mm, and more preferably a range from 200 mm to 500 mm. 
     A tubular member  31  is formed of one tubular shape by connecting a plurality of tubular portions  31 A to  31 F with attachment portions  31 G to  31 K. A tubular member  31  may be formed in one tubular shape without providing an attachment portion. Tubular portions  31 B,  31 C,  31 D,  31 E are formed by tubular portions of the same shape. A tubular portion  31 A is one having a slightly shorter length. A tubular portion  31 F is formed so that the cross-sectional shape becomes smaller toward the tip. Attachment portions  31 G to  31 K connect firmly adjacent tubular portions so as not to come off. 
     As described above, a tubular member  31  is provided with a spiral transfer means  31   a  continuously provided adjacent to an inner wall of a tubular member  31  from an inlet portion  31   b  toward an outlet portion  31   c . The transfer means  31   a  can form a spiral shape by providing a wall portion or a groove in an inner periphery of a tubular member  31 . The formation of a spiral shape also includes a method of embedding a screw in an inner periphery of a tubular member  31 . 
     A transfer means  31   a  transfers a frozen substance entering from an inlet portion  31   b  sequentially in a tubular member  31  located inside of a plurality of regions  40   a  to  40   j , continuously sublimating and drying a frozen substance, and guide a dry substance sublimated and dried to an outlet portion  31   c.    
     Next, a configuration of a rotating portion will be described. 
     As shown in  FIGS.  3  to  6   , a rotating portion  7  is provided with a motor  71 , pulleys  72 ,  73 , a belt  74 , rotational shafts  75 ,  76  and rotary rollers  77 ,  78 . 
     A motor  71  is a rotational drive source. Pulleys  72 ,  73 , a belt  74  and rotational shafts  75 ,  76  function as rotational drive transmitting portions for transmitting rotational drive. Rotary rollers  77 ,  78  are a rotation support portion for supporting a rotation by a rotational drive transmitting portion. A rotation support portion may be configured by adding a bearing to rotary rollers  77 ,  78 , and configured by replacing a rotary roller  77  with a bearing. 
     A belt  74  is hanged on the pulleys  72  and  73 . Rotational force of a motor  71  is transmitted via a belt  74 . A rotary roller  77  is arranged below on both sides of a tubular member  31 . A tubular member  31  is placed on a rotary roller  77  arranged on both sides. 
     A pulley  73  is attached near one end of a rotational shaft  75 . A rotating roller  78  attached to a fixed base is provided inside a pulley  73 , and a rotary roller  78  similarly attached to a fixed base is also provided at the other end of the rotating shaft  75 . Between rotary rollers  78  and  78 , eight rotary rollers  77  are attached to a rotational shaft  75 . 
     A rotational shaft  76  has a rotary roller  78  attached to a fixed base on the one end, and has a rotary roller  78  attached to a fixed base on the other end. Between these rotary rollers  78  and  78 , eight rotary rollers  77  are attached to a rotational shaft  76 . Rotary rollers  77  attached to a rotational shaft  75  are driving rollers, and rotary rollers  77  attached to a rotational shaft  76  are driven rollers. 
     When a motor  71  rotates, a belt  74  rotates through a pulley  72 , a rotational shaft  75  rotates by a rotation of a pulley  73 , and by a rotation of rotary roller  77  fixed to a rotational shaft  75 , a tubular member  31  rotates, and a rotary roller  77  rotates as a driven roller attached to a rotational shaft  76 . 
     Next, a rotation speed of a tubular member  31  will be described. 
     It is preferred that a tubular member  31  rotates by a rotating portion  7  at a rotation speed of 1/30 rpm or more and 1 rpm or less. 
     Next, a temperature detection unit and a moisture detection unit will be described. 
     As shown in  FIGS.  3  and  4   , in a tubular member  31  glass windows (window portion)  36  are continuously provided at a certain intervals in a circumferential direction, and the glass windows  36  are provided at a plurality of locations (eight locations in the present embodiment) in a longitudinal direction of a tubular member  31 . The glass window  36  is provided so that a state of a substance inside can be recognized and detected from outside. A glass window  36  may be made of resin. 
     A detection unit  37  is provided at the lower portion of a tubular member  31  where a glass window  36  is provided in a circumferential direction. A detection unit  37  includes at least three types, and includes a temperature detection unit for detecting a temperature of a substance inside a tubular member  31 , a temperature detection unit for detecting a temperature of an outer surface (wall surface) of a tubular member  31 , and a moisture detection unit for detecting the amount of moisture of a substance inside a tubular member  31 . 
     When a detection unit  37  functions as a temperature detection unit for detecting a temperature of a substance inside a tubular member  31 , it can be configured as a contact type or a non-contact type. When a detection unit  37  functioning as a temperature detection unit is a contact type, it detects a surface temperature of a tubular member  31 . When a detection unit  37  functioning as a temperature detection unit is a non-contact type, it detects a temperature of a substance inside a tubular member  31  through a glass window  36  of a tubular member  31 . 
     A temperature control unit  8  is capable of independently controlling temperatures of temperature adjusting means  30   a  to  30   j , according to a surface temperature of a tubular member  31  or a temperature of a substance inside a tubular member  31  through a glass window  36  which a detection unit  37  detects. 
     Further, when a detection unit  37  functions as a moisture detection unit for detecting the amount of moisture of a substance inside a tubular member  31 , it is capable of detecting the amount of moisture of a substance inside a tubular member  31  through a transparent glass window  36 . A temperature control unit  8  is capable of independently controlling temperature of temperature adjusting means  30   a  to  30   j , according to the amount of moisture of a substance inside a tubular member detected by a detection unit  37 . 
       FIG.  9    shows how a detection unit detects a temperature of a substance or the amount of moisture of a substance inside. 
     As shown in  FIG.  9   , when a detection unit  37  function as a temperature detection unit for detecting a temperature of a substance inside a tubular member  31  and as a moisture detection unit for detecting the amount of moisture of a substance inside a tubular member  31 , it is capable of detecting temperature of a substance X inside a tubular member  31  and a moisture of a substance inside a tubular member  31  through a transparent glass window  36  of a tubular member  31 . 
     A detection unit  37  is capable of detecting a temperature of a substance X inside a tubular member  31  and the amount of moisture of a substance inside a tubular member  31  through each of transparent glass windows  36  provided at a certain intervals in a circumferential direction of a tubular member  31 . Also, since glass windows  36  and detection units  37  are provided at a plurality of positions in a longitudinal direction of a tubular member  31 , a temperature and the amount of moisture of a substance can be accurately detected at each position of the tubular member  31  respectively. 
     Next, a transfer means  31   a  will be described. 
       FIGS.  7 A to  7 E  show a tubular portion  31 B among a plurality of tubular portions  31 A to  31 F constituting a tubular member  31 .  FIG.  7 A  is a perspective view of a tubular portion  31 B shown in  FIG.  3   ,  FIG.  7 B  is a front view of a tubular portion  31 B,  FIG.  7 C  is a side view of a tubular portion  31 B,  FIG.  7 D  is a cross-sectional view of a tubular portion  31 B, and  FIG.  7 E  is a figure enlarging a B portion of  FIG.  7 D .  FIG.  8    shows a half body  31 BX of a tubular portion  31 B. 
     In addition, in  FIGS.  7  and  8   , a showing of glass window  36  is omitted since a spiral transfer means  31   a  is centered in a tubular portion  31 B of  FIG.  3   . 
     As shown in  FIGS.  7  and  8   , a tubular portion  31 B constituting a tubular member  31  is formed of a tubular shape, and edge portions  31   d  protruding in a radial direction in both sides of an opening end are formed. One tubular member  31  is formed by fixing edge portions  31   d  each other of adjacent tubular portions of  31 A to  31 F. The edge portions  31   d  each other of adjacent tubular portions of  31 A to  31 F are fixed by connecting ferrules, clamping, or bolting. 
     A part of a spiral transfer means  31   a  is continuously formed in a tubular portion  31 B from one end to the other end. 
     As shown in  FIG.  7 E , a wall portion is continuously formed in an inner wall of a tubular portion  31 BX as a part of a transfer means  31   a , such as a wall portion  31   a   1  in first lap and a wall portion  31   a   2  in a second lap, so that a part of a transfer means  31   a  can be formed in a tubular portion  31 BX. 
     A height of a wall portion  31   a   1  and a wall portion  31   a   2  is a height of a transfer means  31   a , and is preferably configured in a range of, for example, 3 mm or more and 50 mm or less. 
     A pitch of a wall portion  31   a   1  and a wall portion  31   a   2  is a pitch of a spiral transfer means  31   a , and is preferably configured in a range of, for example, 5 mm or more and 20 mm or less. 
       FIG.  8    shows a half body  31 BX of a tubular portion  31 B, by combining two of these half bodies  31 BX, one tubular portion  31 B is constituted. A half body  31 BX of a tubular portion  31 B is capable of forming a part of a spiral transfer means  31   a  in a tubular portion  31 B when the two are combined. 
       FIG.  10    is a cross-sectional view of a connection portion of a vacuum freeze-drying apparatus according to an embodiment. 
     As shown in  FIG.  10   , a connection portion  4  is provided between a collecting portion  22  of a vacuum freezing device  2  and an end portion in an inlet  31   b  side of a drying device  3 , is for transporting a frozen substance produced by a vacuum freezing device  2  to a drying device  3 . Near an end portion  301 , a receiving port  302  is provided for receiving a frozen substance transported by a connection portion  4 . 
     A connection portion  4  comprises an inner pipe portion  41 , an outer pipe portion  42 , a screw  43  provided in the inner pipe portion  41 , and an intermediate pipe portion  44  extending from an end portion  301  of a drying device  3  to an inner pipe portion  41  and an outer pipe portion  42  of a connection portion  4 . Between an outer pipe portion  42  and an intermediate pipe portion  44 , a bearing  45  and an air seal  46  are provided from a drying device  3  side. 
     An air seal  46  is for sealing a rotating shaft by supplying air from a flow path without contacting a rotating shaft. 
       FIG.  11    is a diagram showing another example of a half body  31 BX of a tubular portion  31 B of  FIGS.  7 A to  7 E . 
     In examples shown in  FIGS.  7  and  8   , a wall portion is formed in an inner wall of a tubular member  31  to form a transfer means  31   a . But as shown in  FIG.  11   , groove portions  131   a   1 ,  131   a   2  . . . may be formed in an inner wall of a tubular member  31  to form a transfer means  131   a.    
     A tubular portion  31 B is capable of forming one tubular portion  31 B by connecting two half bodies  131 BX. When two half bodies  131 BX of a tubular portion  31 B are connected, groove portions forming a spiral transfer means  131   a  are respectively formed continuously. A depth of a groove portion  131   a   1  and a groove portion  131   a   2  is a depth of a transfer means  131   a , and is preferably configured in a range of, for example, 3 mm or more and 50 mm or less. A pitch of a groove portion  131   a   1  and a groove portion  131   a   2  is a pitch of a transfer means  131   a , and is preferably configured in a range of, for example, 5 mm or more and 20 mm or less. 
     By forming a spiral groove portion in an inner periphery surface of a tubular member  31  as a transfer means  131   a  centered on a rotating shaft, a spiral feeding action inside of a tubular member  31  is imparted, and a frozen substance or a dry substance can be transferred continuously. 
     According to the present embodiment, it is possible to provide a vacuum freeze-drying apparatus and a vacuum freeze-drying method capable of continuously performing vacuum freeze-drying in a short time. 
     A vacuum freeze-drying method of the present embodiment includes a vacuum freezing step of freezing a liquid, a drying step of sublimating and drying a frozen substance frozen, and a step of performing vacuum suction through an exhaust path. The drying step comprises a step of rotating a tubular member  31  which is a tubular member  31  formed of a tubular shape having an inlet portion  31   b  and an outlet portion  31   c , having a spiral transfer means  31   a  continuously provided adjacent to an inner wall of a tubular member  31  from an inlet portion  31   b  toward an outlet portion  31   c , a step of adjusting temperatures of a plurality of at least three or more regions  40   a  to  40   j  provided from an inlet portion  31   b  toward an outlet portion  31   c  in a peripheral portion of a tubular member  31 , whose temperatures are capable of being controlled, and a step of continuously sublimating and drying the frozen substance entering from an inlet portion  31   b , while transferring the frozen substance sequentially to locations corresponding to a plurality of regions  30   a  to  30   j  in a tubular member  31  by a transfer means  31   a.    
     Next, another structure of the connection portion  4  will be described with reference to  FIG.  12   .  FIG.  12    is a cross-sectional view of the connection portion  4 B of the vacuum freeze-drying apparatus according to another embodiment of the present invention. 
     First, in the vacuum freeze-drying apparatus provided with a vacuum freeze device  2  for freezing the liquid and a drying device  3  for sublimating and drying the frozen product, configured to move the frozen product from the vacuum freeze device  2  to the drying device  3  through the connection portion  4 B, the connection portion  4 B is configured so that the frozen product is moved by a screw  58  provided in the transfer pipe  55  facing the collecting section  22  of the vacuum freezing device  2  in the axial direction. However, the transfer of the screw  43  does not necessarily in the horizontal direction, and the frozen product may be transferred to the tubular portion  31 . 
     The base end portion (left end portion) of the screw  58  is supported by a bearing portion  56  (here, a bearing), a first suction port  53  is provided in the vicinity of the bearing portion, and it is configured that the inside of the transfer pipe  55  is maintained to constantly be in a vacuum (a high degree of vacuum is sufficient). The first suction port  53  is connected to a vacuum pump, but illustration and description thereof will be omitted. 
     A tip portion of the transfer pipe  55  is configured to be a bearing portion  51 , configured to rotationally support an end member  52  of the tubular portion  31 A of the tubular portion  31  of the drying device. And a second suction port  54  is provided facing between the end member  52  and the bearing portion  51 , it is configured that the inside of the transfer pipe  55  and the inside of the tubular portion  31  are maintained to in a vacuum. The suction port  54  is connected to the vacuum pump, but illustration and description thereof will be omitted here. 
     The screw  58  is a spiral coil structure arranged around a rotating shaft  57 , and provided in a state close to the inner wall of the transfer pipe  55 , and it is configured that the frozen material received from the collecting portion  22  is fed into the tubular portion  31  by the rotation thereof. The coil structure may be spiral shape, and may be a structure in which fragments form a substantial coil, and in short, it may be a structure capable of exhibiting a continuous feed function. The above-mentioned close state provision is to provide a clearance between the coil structure and the transfer pipe  55  so that the frozen material is not to be caught and damaged. 
     A motor  60  for driving and a coupling  59  for transmitting the driving force of the motor  60  to the rotating shaft  57  are arranged at an end of the rotating shaft  57  opposite side to the tubular portion  31 . As described above, by providing a motor  60  for rotationally driving the screw  58  separately from the motor  71  for rotationally driving the tubular portion  31 , it is possible to arbitrarily change the transport of the frozen material to the drying device  3 , for example upping the rotation speed of the motor  60 , to increase the transport amount. Further, in the connection portion  4  (see  FIG.  10   ), since the end portion of the screw  43  on the drying device  3  side is necessary mechanically connected to the tubular portion  31 A of the tubular portion  31 , the structure of the boundary portion between the connection portion  4  and the tubular portion  31  becomes complicated, although in the connection portion  4 B of an another form, since the tip of the screw  58  enters in the tubular portion  31 , there is an advantage that a transport of the frozen material can be efficiently done. 
     Although the present invention has been described using above embodiments, it goes without saying that the technical scope of the present invention is not limited to the scope of the above embodiments, and it is clear to those skilled persons in the art that various modifications or improvements added to the above embodiments are possible. Further, it is clear from the description of the scope of claims that the form to which such modifications or improvements are added may be included in the technical scope of the present invention. 
     DESCRIPTION OF INDEXES 
     
         
           1  Vacuum freeze-drying apparatus 
           2  Vacuum freezing device 
           3  Drying device 
           4  Connection portion 
           4 B Connection portion 
           6  Clean air 
           7  Rotating portion 
           8  Temperature control unit 
           30   a  to  30   j  Temperature adjusting means 
           31  Tubular member 
           31   a  Spiral transfer means 
           36  Glass window (window portion) 
           37  Detection unit (temperature detection portion, moisture detection portion) 
           40   a  to  40   j  Regions 
           46  Air seal