Patent Document

TECHNICAL FIELD 
     The present invention relates to a device and a preparation method for mixing a continuous phase and a dispersed phase with each other so as to form an emulsion. 
     BACKGROUND ART 
     As emulsion preparation devices in the field of medical equipment, chemical liquid preparation connectors described in Patent Documents 1 and 2 are reported. According to these connectors, a syringe charged with a continuous phase is linked to one side and a syringe charged with a dispersed phase is linked to the other side. Then, when pumping operation is performed alternately on both syringes, both phases are mixed with each other so that an emulsion is formed. 
     Nevertheless, in the connector of Patent Document 1, according to investigation by the present inventors, it has been recognized that: a large amount of pumping operation is necessary for forming a sufficient emulsion; further, depending on the composition of the chemical liquid, a sufficient emulsion cannot be formed in some cases; and further, an inconvenience of relatively high sliding resistance is present at the time of pumping operation. Further, the connector of Patent Document 1 does not include a filter part. A filter part in the connector of Patent Document 2 employs a porous material fabricated from a glass membrane. None of the connectors of both documents includes a filter part filled with fibers. Patent Document 3 relates to a filter filled with fibers but does not describe an emulsion preparation device. Further, Patent Document 4 also does not describe a connector provided with a filter part filled with fibers. 
     PRIOR ART REFERENCES 
     Patent Documents 
     Patent Document 1: International Publication No. 2007/083763 
     Patent Document 2: Japanese Unexamined Patent Application Publication No. 2005-186026 
     Patent Document 3: Japanese Examined Patent Application Publication No. S52-35235 
     Patent Document 4: Japanese Unexamined Patent Application Publication No. 2006-346565 
     SUMMARY OF THE INVENTION 
     Problem to be Solved by the Invention 
     An object of the present invention is to provide an emulsion preparation device and an emulsion preparation method capable of forming an emulsion in a chemical liquid of diverse composition and further realizing a relatively low sliding resistance. 
     Means for Solving the Problem 
     The present invention is characterized by an emulsion preparation device provided with a filter part, wherein: the filter part is constructed from a first and a second mesh part and fibers; and the fibers are loaded into a space between the first mesh part and the second mesh part. That is, the present invention provides the following (1) to (12). 
     (1) An emulsion preparation device provided with a filter part, wherein: 
     the filter part is constructed from a first and a second mesh part and fibers; 
     and the fibers are loaded into a space between the first mesh part and the second mesh part. 
     (2) The emulsion preparation device according to the above-mentioned (1), wherein: 
     one side or both sides of the filter part can be connected to a syringe; and 
     an emulsion is formed when a continuous phase and a dispersed phase perform, through the filter part, reciprocating movement between two syringes linked to the both sides of the filter part or alternatively between a syringe linked to one side and a vessel linked to the other side. 
     (3) The emulsion preparation device according to the above-mentioned (1) or (2), wherein 
     the first mesh part and/or the second mesh part are disks. 
     (4) The emulsion preparation device according to the above-mentioned (3), wherein 
     the mesh part includes a large number of through holes of arc shape arranged uniformly in a concentric manner and all the through holes have the same area as each other within an error range of 10%. 
     (5) The emulsion preparation device according to any one of the above-mentioned (1) to (4), wherein 
     the fibers are of a hydrophobic fiber. 
     (6) The emulsion preparation device according to the above-mentioned (5), wherein 
     the hydrophobic fiber is polyester. 
     (7) The emulsion preparation device according to any one of the above-mentioned (1) to (4), wherein 
     the fibers are of a hydrophilic fiber. 
     (8) The emulsion preparation device according to any one of the above-mentioned (1) to (7), wherein 
     the fibers have 50 to 150 deniers and are loaded such that 2.5 to 17.7 mm are present per 1 mm 3  of the space. 
     (9) The emulsion preparation device according to any one of the above-mentioned (1) to (8), wherein 
     the fibers have 50 to 150 deniers and are loaded such that 5.0 to 9.9 mm are present per 1 mm 3  of the space. 
     (10) The emulsion preparation device according to any one of the above-mentioned (1) to (9), constructed from 
     a first cylindrical member and a second cylindrical member, wherein: 
     the first cylindrical member is constructed from a first cylinder part and a second cylinder part continuous to the first cylinder part; 
     the second cylinder part has a smaller diameter than the first cylinder part; 
     in the first cylindrical member, the first mesh part is formed at a boundary between the first cylinder part and the second cylinder part, the fibers are pushed in toward the first mesh part, the second mesh part is pushed against the fibers, and, as a result, the filter part constructed from the first mesh part, the fiber aggregate, and the second mesh part is formed; 
     the second mesh part is a bottom face of a concave lid fit onto the first cylinder part; 
     in the concave lid, an outer flange in an aperture periphery abuts against an aperture periphery of the first cylinder part so that the second mesh part is positioned in the inside of the first cylinder part at a predetermined distance to the first mesh part and in parallel thereto; and 
     the first cylindrical member and the second cylindrical member are joined into a single piece by the outer flange in the aperture periphery of the first cylinder part and an outer flange in an aperture periphery of the second cylindrical member. 
     (11) The emulsion preparation device according to any one of the above-mentioned (1) to (9), constructed from 
     a first cylindrical member and a second cylindrical member, wherein: 
     the first cylindrical member is constructed from a first cylinder part and a second cylinder part continuous to the first cylinder part; 
     the second cylinder part has a smaller diameter than the first cylinder part; 
     in the first cylindrical member, the first mesh part is formed at a boundary between the first cylinder part and the second cylinder part, the fibers are pushed in toward the first mesh part, the second mesh part is pushed against the fibers, and, as a result, the filter part constructed from the first mesh part, the fiber aggregate, and the second mesh part is formed; 
     the second mesh part is a bottom face of a concave lid fit onto the first cylinder part; 
     in the concave lid, an outer flange in an aperture periphery abuts against an aperture periphery of the first cylinder part so that the second mesh part is positioned in the inside of the first cylinder part at a predetermined distance to the first mesh part and in parallel thereto; 
     the first cylindrical member and the second cylindrical member are joined into a single piece by the outer flange in the aperture periphery of the first cylinder part and an outer flange in an aperture periphery of the second cylindrical member; 
     the fiber aggregate is located in a center of a longitudinal direction; and 
     in a state that the first cylindrical member and the second cylindrical member have been joined into a single piece, an external shape is bilaterally symmetric in the longitudinal direction. 
     (12) An emulsion preparation method employing the emulsion preparation device according to any one of the above-mentioned (1) to (11). 
     The emulsion preparation method according to the present invention is characterized by employing the above-mentioned emulsion preparation device according to the present invention. 
     Effect of the Invention 
     According to the present invention, in a chemical liquid of diverse composition, an emulsion can be formed and further the sliding resistance can be made relatively low. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  is an overall side view of a preparation instrument employing an emulsion preparation device of a first embodiment of the present invention. 
         FIG. 2  is a sectional side view of a device of  FIG. 1 . 
         FIG. 3  is a view taken in an arrow III direction in  FIG. 1  and showing a first mesh part. 
         FIG. 4  is an overall side view of a preparation instrument employing an emulsion preparation device of a second embodiment of the present invention. 
         FIG. 5  is a side view of a device of  FIG. 4 . 
         FIG. 6  is a sectional side view of a device of  FIG. 4 . 
         FIG. 7  is a transparent side view of a device of  FIG. 4 . 
         FIG. 8  is a diagram showing a modification of a first mesh part. 
         FIG. 9  is a diagram showing another modification of a first mesh part. 
         FIG. 10  is a diagram showing a drop test in emulsion check tests A and B. 
         FIG. 11  is a diagram showing a step in a method of sliding resistance evaluation tests A and B. 
         FIG. 12  is a diagram showing a step in a method of foreign substance evaluation test. 
     
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     First Embodiment 
       FIG. 1  is an overall side view of a preparation instrument employing an emulsion preparation device of a first embodiment of the present invention. The preparation instrument  100  is constructed from a device  1  and syringes  8  and  9  linked to both sides of the device  1 . The syringe  8  is constructed from a cylinder  81  and a plunger  82 . The syringe  9  is constructed from a cylinder  91  and a plunger  92 . 
       FIG. 2  is a sectional side view of the device  1 . The device  1  is constructed such that the first cylindrical member  2  and the second cylindrical member  4  are joined into a single piece by outer flanges  29  and  49  in the aperture periphery. Here, it is preferable that the device  1  is constructed from a sterilizable material. 
     The first cylindrical member  2  is constructed from a first cylinder part  21  and a second cylinder part  22  continuous to the first cylinder part  21 . The second cylinder part  22  has a smaller diameter than the first cylinder part  21 . In the first cylindrical member  2 , a first mesh part  31  is formed at the boundary between the first cylinder part  21  and the second cylinder part  22 . 
     Then, in the first cylindrical member  2 , fibers  32  are pushed in toward the first mesh part  31  and the second mesh part  33  is pushed against the fibers  32 . That is, the fibers  32  are pushed and loaded into a space  30  between the first mesh part  31  and the second mesh part  33 . The first mesh part  31 , the fibers  32 , and the second mesh part  33  constitute a filter part  10 . Here, the first mesh part  31  and the second mesh part  33  are disks provided with a large number of through holes. The fibers  32  loaded in the space  30  constitute a fiber aggregate filling the space  30 . In the fiber aggregate, a large number of small voids are formed between the fibers. Thus, in the filter part  10 , liquid can move back and forth from the first mesh part  31  to the second mesh part  33  and vice versa passing through the voids in the fiber aggregate. 
     The second mesh part  33  is the bottom face of a concave lid  23  fit onto the first cylinder part  21 . In the concave lid  23 , the outer flange  231  in the aperture periphery abuts against the aperture periphery  211  of the first cylinder part  21  so that the second mesh part  33  is positioned in the inside of the first cylinder part  21  at a predetermined distance to the first mesh part  31  and in parallel thereto. 
     A luer taper  48  is formed at the aperture end of the second cylindrical member  4 . A luer taper  28  is formed also at the aperture end of the second cylinder part  22  of the first cylindrical member  2 . The first cylindrical member  2  and the second cylindrical member  4  are in fluid communication with each other through apertures  20  and  40  of the same size as each other. 
       FIG. 3  is a view of the first mesh part  31  taken in the arrow III direction. The first mesh part  31  includes a large number of through holes  311  (i.e., through holes  311   a ,  311   b , and  311   c ) of arc shape arranged uniformly in a concentric manner. All the through holes  311  have the same area as each other within an error range of 10%. The second mesh part  33  also has the same configuration as the first mesh part  31 . 
     The fibers  32  are of a hydrophobic fiber. As the hydrophobic fiber, polyester, polypropylene, polystyrene, Teflon (registered trademark), nylon, polyvinyl chloride, acrylics, or the like may be employed. However, polyester is preferable. It is preferable that the fibers  32  are crimped. The fibers  32  have 50 to 150 deniers and are loaded into the space  30  such that 2.5 to 17.7 mm are present per 1 mm 2  of the  2 C space  30 . Here, it is preferable that loading is performed such that 4.0 to 12.0 mm are present, and it is more preferable that loading is performed such that 5.0 to 9.9 mm are present. 
     The preparation instrument  100  shown in  FIG. 1  is used as follows. That is, an emulsion preparation method employing the device  1  is as follows. Here, in the preparation instrument  100 , the syringe  8  is charged with a dispersed phase  101  and the syringe  9  is charged with a continuous phase  102 . However, a reversed situation may be employed. 
     First, the plunger of one syringe is pushed. For example, pumping operation in the direction A is performed on the plunger  82  of the syringe  8 . By virtue of this, the dispersed phase  101  moves through the device  1  to the syringe  9  so that the plunger  92  of the syringe  9  is pushed aside in the direction A. At that time, in the syringe  9 , the dispersed phase  101  is somewhat mixed with the continuous phase  102 . 
     Next, pumping operation in the direction B is performed on the plunger  92  of the syringe  9 . By virtue of this, the dispersed phase  101  and the continuous phase  102  somewhat mixed with each other move through the device  1  to the syringe  8  so that the plunger  82  of the syringe  8  is pushed aside in the direction B. At that time, in the device  1 , both phases  101  and  102  somewhat mixed with each other pass through the filter part  10 . That is, both phases  101  and  102  somewhat mixed with each other first pass through the second mesh part  33  so as to be dispersed and mixed at that time, then pass through the fibers  32  so as to be further dispersed and mixed at that time, and then pass through the first mesh part  31  so as to be further dispersed and mixed at that time. Thus, both phases  101  and  102  having moved to the syringe  8  are in a state of being mixed more than in the syringe  9 . 
     Next, pumping operation in the direction A is performed on the plunger  82  of the syringe  8 . By virtue of this, both phases  101  and  102  mixed more with each other move through the device  1  to the syringe  9  so that the plunger  92  of the syringe  9  is pushed aside in the direction A. At that time, in the device  1 , both phases  101  and  102  mixed more with each other pass through the filter part  10 . That is, both phases  101  and  102  mixed more with each other first pass through the first mesh part  31  so as to be dispersed and mixed at that time, then pass through the fibers  32  so as to be further dispersed and mixed at that time, and then pass through the second mesh part  33  so as to be further dispersed and mixed at that time. Thus, both phases  101  and  102  having moved to the syringe  9  are in a state of being mixed more than in the syringe  8 . 
     As such, pumping operation on the plunger  82  of the syringe  8  and pumping operation on the plunger  92  of the syringe  9  are repeated alternately. It is preferable that the number of times of the pumping operation is 50 times or smaller. Further, ten times or smaller is more preferable and five times or smaller is the most preferable. By virtue of this, the state of mixing of both phases  101  and  102  progresses further into a state of emulsion which is a target state. Here, the fibers  32  are of a hydrophobic fiber. Thus, the oil phase serves as a continuous phase and the aqueous phase serves as a dispersed phase so that a water-in-oil type emulsion is formed. 
     According to the device  1  of the configuration, the fibers  32  have 50 to 150 deniers and are loaded into the space  30  such that 2.5 to 17.7 mm are present per 1 mm 3  of the space  30 . Thus, both phases  101  and  102  can be dispersed and mixed efficiently so that a desired emulsion can be formed. 
     Further, in the first mesh part  31  and the second mesh part  33 , the through holes  311  of the same area as each other are arranged uniformly. Thus, dispersion of both phases  101  and  102  occurs uniformly in the entire region of the mesh part. Thus, also from this point, both phases  101  and  102  can be dispersed and mixed efficiently. 
     Further, the fibers  32  filling the space  30  have predetermined thickness and length. Further, the first mesh part  31  and the second mesh part  33  include a large number of the through holes  311  of arc shape and hence have a large void ratio. Thus, the sliding resistance at the time of pumping operation can be reduced. This improves the operability. 
     Second Embodiment 
       FIG. 4  is an overall side view of a preparation instrument employing an emulsion preparation device of a second embodiment of the present invention. The preparation instrument  100  is constructed from a device  1 A and syringes  8  and  9  linked to both sides of the device  1 A. The syringe  8  is constructed from a cylinder  81  and a plunger  82 . The syringe  9  is constructed from a cylinder  91  and a plunger  92 . 
       FIG. 5  is a side view of the device  1 A.  FIG. 6  is a sectional side view of the device  1 A. The device  1 A is different from the device  1  of the first embodiment in the following points. 
     (i) The aggregate of the fibers  32  filling the space  30  is located in the center of the longitudinal direction. 
     (ii) The external shape is bilaterally symmetric in the longitudinal direction. 
     (iii) Liquid surface adjustment ribs  93  and  95  are provided. 
     That is, the difference is as follows. 
     The device  1 A is constructed such that the first cylindrical member  2  and the second cylindrical member  4  are joined into a single piece by outer flanges  29  and  49  in the aperture periphery. Here, it is preferable that the device  1 A is constructed from a sterilizable material. 
     The first cylindrical member  2  is constructed from a first cylinder part  21  and a second cylinder part  22  continuous to the first cylinder part  21 . The second cylinder part  22  has a smaller diameter than the first cylinder part  21 . In the first cylindrical member  2 , a first mesh part  31  is formed at the boundary between the first cylinder part  21  and the second cylinder part  22 . 
     Then, in the first cylindrical member  2 , fibers  32  are pushed in toward the first mesh part.  31  and the second mesh part  33  is pushed against the fibers  32 . That is, the fibers  32  are loaded into a space  30  between the first mesh part  31  and the second mesh part  33 . The first mesh part  31 , the fibers  32 , and the second mesh part  33  constitute a filter part  10 . Here, the first mesh part  31  and the second mesh part  33  are disks provided with a large number of through holes. The fibers  32  filling the space  30  constitute a fiber aggregate filling the space  30 . In the fiber aggregate, a large number of small voids are formed between the fibers. Thus, in the filter part  10 , liquid can move back and forth from the first mesh part  31  to the second mesh part  33  and vice versa passing through the voids in the fiber aggregate. 
     The second mesh part  33  is the bottom face of a concave lid  23  fit onto the first cylinder part  21 . In the concave lid  23 , the outer flange  231  in the aperture periphery abuts against the aperture periphery  211  of the first cylinder part  21  so that the second mesh part  33  is positioned in the inside of the first cylinder part  21  at a predetermined distance to the first mesh part  31  and in parallel thereto. 
     The first cylindrical member  2  and the second cylindrical member  4  are in fluid communication with each other through apertures  20  and  40  of the same size as each other. 
     Then, the aggregate of the fibers  32  filling the space  30  is located in the center of the longitudinal direction. That is, the space  30  is located in the center of the longitudinal direction. 
     Further, as seen From  FIG. 5 , the external shape of the device  1 A is bilaterally symmetric in the longitudinal direction. That is, the first cylindrical member  2  includes an outer flange  29  in the aperture periphery, a large flange  91 , a small flange  92 , a liquid surface adjustment rib  93 , and a connection end part  94 . On the other hand, the second cylindrical member  4  includes an outer flange  49  in the aperture periphery, a liquid surface adjustment rib  95 , and a connection end part  96 . Then, when the first cylindrical member  2  and the second cylindrical member  4  abut against each other at the outer flange  29  and the outer flange  49  so as to be joined together, in the device  1 A, the large flange  91  is located in the center of the longitudinal direction. Further, on both sides thereof, the small flange  92  and the outer flanges  29  and  49  joined into a single piece are located similarly. Furthermore, on both sides thereof, the liquid surface adjustment rib  93  and the liquid surface adjustment rib  95  are located similarly. Further, on both sides thereof, the connection end part  94  and the connection end part  96  are located similarly. As a result, the device  1 A is bilaterally symmetric in the longitudinal direction. 
     The first mesh part  31 , the fibers  32 , and the second mesh part  33  are the same as those in the first embodiment. 
     When the preparation instrument  100  shown in  FIG. 4  is used similarly to the first embodiment, an emulsion can be formed similarly to the first embodiment. 
     Further, in the device  1 A, as shown in  FIG. 7 , parts where the formed emulsion remains are spaces  71  and  72 , whose volumes are small. Thus, according to the device  1 A, the generation efficiency for an emulsion can be improved. 
     Further, in the device  1 A, the liquid surface adjustment ribs  93  and  95  indicate the upper limits for the height positions of the continuous phase and the dispersed phase at the time of air vent, and serve as guides used when the plungers  82  and  92  are pushed for air vent. Thus, according to the device  1 A, the workability of air vent can be improved. 
     [Modified Structures] 
     The following modified structures may be adopted. 
     (1) The fibers  32  may be of a hydrophilic fiber. For example, cotton, rayon, vinylon, or the like may be employed. In this case, the aqueous phase serves as a continuous phase and the oil phase serves as a dispersed phase so that an oil-in-water type emulsion is formed. 
     (2) The first mesh part  31  and the second mesh part  33  may be disks as shown in  FIG. 8 or 9 . The mesh part in  FIG. 8  includes a large number of through holes  312  (i.e., through holes  312   a ,  312   b , and  312   c ) of arc shape aligned in a concentric manner. Then, the area of each through hole  312  becomes larger as being located in the outer side. The mesh part in  FIG. 9  includes a large number of circular holes  313  distributed uniformity. Then, all the circular holes  313  have the same area as each other. 
     (3) The first mesh part  31  and the second mesh part  33  may have a shape other than the disk and, for example, may have the shape of a block. 
     (4) A mixed solution of a dispersed phase and a continuous phase may be loaded in any one of the syringe  8  and the syringe  9 . In this case, no liquid is loaded in the other one. 
     EXAMPLES 
     The device  1  of examples 1 to 14 and the device  1 A of example 15 were prepared. Then, emulsion check test A and sliding resistance evaluation test A were performed on the device  1  of examples 1 to 11. Further, emulsion check test B and sliding resistance evaluation test B were performed on the device  1  of examples 12, 13, and 14. Emulsion check test B was performed on the device  1 A of example 15. Sliding resistance evaluation test C and foreign substance evaluation test were performed on the device  1  of example 12 and the device  1 A of example 15. 
     Example 1 
     The device  1  having the configuration of  FIG. 2 . Detailed dimensions and the like are as follows. Here, the fibers  32  are crimped and loaded into the space  30 .
         Space  30 :
           56.52 mm 3      
           Fibers  32 :
           Polyester   50 deniers   1000 mm (17.7 mm is present per 1 mm 3  of space  30 )   
           First mesh part  31  and second mesh part  33 :
           Configuration of  FIG. 3 
               Through hole  311   a:  0.43 mm 2      Through hole  311   b:  0.45 mm 2      Through hole  311   c:  0.46 mm 2      Opening area: 5.42 mm 2      
               
               

     Example 2 
     The following point alone is different from example 1.
         Fibers  32 :
           560 mm (9.9 mm is present per 1 mm 3  of space  30 )   
               

     Example 3 
     The following point alone is different from example 1.
         Fibers  32 :
           280 mm (5.0 mm is present per 1 mm 3  of space  30 )   
               

     Example 4 
     The following point alone is different from example 1.
         Fibers  32 :
           140 mm (2.5 mm is present per 1 mm of space  30 )   
               

     Example 5 
     The following point alone is different from example 1.
         Fibers  32 :
           100 deniers   
               

     Example 6 
     The following points alone are different from example 1.
         Fibers  32 :
           100 deniers   560 mm (9.9 mm is present per 1 mm of space  30 )   
               

     Example 7 
     The following points alone are different from example 1.
         Fibers  32 :
           100 deniers   280 mm (5.0 mm is present per 1 mm 3  of space  30 )   
               

     Example 8 
     The following points alone are different from example 1.
         Fibers  32 :
           100 deniers   140 mm (2.5 mm is present per 1 mm 3  of space  30 )   
               

     Example 9 
     The following points alone are different from example 1.
         Fibers  32 :
           150 deniers   560 mm (9.9 mm is present per 1 mm 3  of space  30 )   
               

     Example 10 
     The following points alone are different from example 1.
         Fibers  32 :
           150 deniers   280 mm (5.0 mm is present per 1 mm of space  30 )   
               

     Example 11 
     The following points alone are different from example 1.
         Fibers  32 :
           150 deniers   140 mm (2.5 mm is present per 1 mm of space  30 )   
               

     Example 12 
     The following points alone are different from example 1.
         Fibers  32 :
           75 deniers   280 mm (5.0 mm is present per 1 mm 3  of space  30 )   
               

     Example 13 
     The following points alone are different from example 12.
         First mesh part  31  and second mesh part  33 :
           Configuration of  FIG. 8 
               Through hole  312   a:  0.17 mm 2      Through hole  312   b:  0.18 mm 2      Through hole  312   c:  0.35 mm 2      Opening area: 4.92 mm 2      
               
               

     Example 14 
     The following points alone are different from example 12.
         First mesh part  31  and second mesh part  33 :
           Configuration of  FIG. 9 
               Through hole  313 : 0.07 mm 2      Opening area: 2.45 mm 2      
               
               

     Example 15 
     The device  1 A having the configuration of  FIG. 6 . Detailed dimensions and the like are as follows. Here, the fibers  32  are crimped and loaded into the space  30 .
         Space  30 :
           56.52 mm 3      
           Fibers  32 :
           Polyester   75 deniers   280 mm (5.0 mm is present per 1 mm 3  of space  30 )   
           First mesh part  31  and second mesh part  33 :
           Configuration of  FIG. 3     Through hole  311   a:  0.43 mm 2      Through hole  311   b:  0.45 mm 2      Through hole  311   c:  0.46 mm 2      Opening area: 5.42 mm 2      
               

     (Emulsion Check Test A) 
     [Test Method] 
     As shown in  FIGS. 1 and 10 , the following procedure was employed. 
     (1) The preparation instrument  100  of  FIG. 1  was prepared. Then, 1.5 ml of 2% L-arginine aqueous solution serving as a dispersed phase, that is, an aqueous phase, was loaded into the space  8 . Then, 1.5 ml of Montanide (official name: Montanide ISA 51VG) serving as a continuous phase, that is, an oil phase, was loaded into the syringe  9 . Here, the syringes  8  and  9  were B BRAUN-fabricated and had a capacity of 5 ml. 
     (2) Pumping operation was manually performed alternately on the plunger  82  of the syringe  8  and the plunger  92  of the syringe  9 . This operation was repeated 5 times. As a result, both phases were accommodated into the syringe  8 . 
     (3) The syringe  9  was removed. Then, as shown in  FIG. 10 , a mixed solution of physiological saline solution and Montanide in the cylinder  8  was dripped through the device  1  to the surface  521  of the water in the vessel  52 . That so-called “drop test” was performed. 
     [Results] 
     Table 1 shows test results. Each test was performed three times. 
     
       
         
               
               
               
             
               
               
               
               
             
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE 1 
               
             
             
               
                   
               
               
                   
                 Fibers 
                 Emulsion check 
               
             
          
           
               
                   
                 Thickness 
                 Length 
                 test A 
               
             
          
           
               
                   
                 Ex. 
                 (denier) 
                 (mm) 
                 First 
                 Second 
                 Third 
               
               
                   
               
             
          
           
               
                   
                 1 
                 50 
                 1000 
                 ∘ 
                 ∘ 
                 ∘ 
               
               
                   
                 2 
                 50 
                 560 
                 ∘ 
                 ∘ 
                 ∘ 
               
               
                   
                 3 
                 50 
                 280 
                 ∘ 
                 ∘ 
                 ∘ 
               
               
                   
                 4 
                 50 
                 140 
                 x 
                 ∘ 
                 x 
               
               
                   
                 5 
                 100 
                 1000 
                 ∘ 
                 ∘ 
                 ∘ 
               
               
                   
                 6 
                 100 
                 560 
                 ∘ 
                 ∘ 
                 ∘ 
               
               
                   
                 7 
                 100 
                 280 
                 ∘ 
                 ∘ 
                 ∘ 
               
               
                   
                 8 
                 100 
                 140 
                 ∘ 
                 ∘ 
                 x 
               
               
                   
                 9 
                 150 
                 560 
                 ∘ 
                 ∘ 
                 ∘ 
               
               
                   
                 10 
                 150 
                 280 
                 ∘ 
                 ∘ 
                 ∘ 
               
               
                   
                 11 
                 150 
                 140 
                 x 
                 ∘ 
                 x 
               
               
                   
               
             
          
         
       
     
     When dripped liquid does not diffuse over the surface  521 , an emulsion has been formed satisfactorily. This situation is indicated by “∘” in the test result. When dripped liquid diffuses over the surface  521 , an emulsion has not been formed. This situation is indicated by “x” in the test result. 
     As seen from Table 1, in examples 1 to 11, a desired emulsion has been formed. In particular, in examples 1, 2, 3, 5, 6, 7, 9, and 10, a satisfactory emulsion has been formed. 
     (Emulsion Check Test B) 
     [Test Method] 
     As shown in  FIGS. 1 and 10 , the following procedure was employed. 
     (1) The preparation instrument  100  of  FIG. 1  was prepared in examples 12 to 14 and the preparation instrument  100  of  FIG. 4  was prepared in example 15. Then, 1.5 ml of 2% L-arginine aqueous solution serving as a dispersed phase, that is, an aqueous phase, was loaded into the space  8 . Then, 1.5 ml of Montanide serving as a continuous phase, that is, an oil phase, was loaded into the space  9 . Here, the syringes  8  and  9  were B BRAUN-fabricated and had a capacity of 5 ml. 
     (2) Pumping operation of alternately pushing on the plunger  82  of the syringe  8  and the plunger  92  of the syringe  9  was performed manually. This operation was repeated 5 times. As a result, both phases were accommodated into the syringe  8 . 
     (3) The syringe  9  was removed. Then, as shown in  FIG. 10 , a mixed solution of L-arginine aqueous solution and Montanide in the cylinder  8  was dripped through the device  1  to the surface  521  of the water in the vessel  52 . That is, a so-called “drop test” was performed. Further, at that time, the presence or absence of falling out of the fibers  32  in the device  1  was also investigated. 
     [Results] 
     Table 2 shows test results. Each test was performed twice. 
     
       
         
               
               
               
               
               
             
               
               
               
               
               
             
           
               
                 TABLE 2 
               
             
             
               
                   
               
               
                   
                   
                   
                 Emulsion 
                   
               
               
                   
                 Mesh 
                   
                 check test B 
                 Fiber 
               
             
          
           
               
                 Ex. 
                 part 
                 First 
                 Second 
                 falling out 
               
               
                   
               
               
                 12 
                 FIG. 3 
                 ∘ 
                 ∘ 
                 None 
               
               
                 13 
                 FIG. 8 
                 ∘ 
                 ∘ 
                 None 
               
               
                 14 
                 FIG. 9 
                 ∘ 
                 ∘ 
                 None 
               
               
                 15 
                 FIG. 3 
                 ∘ 
                 ∘ 
                 None 
               
               
                   
               
             
          
         
       
     
     The meanings of “∘” and “x” in the test results are the same as in emulsion check test A. 
     As seen from Table 2, even when the first mesh part  31  and the second mesh part  33  had whichever configuration of  FIGS. 3, 8, and 9 , a satisfactory emulsion has been formed. 
     (Sliding Resistance Evaluation Test A) 
     [Test Method] 
     As shown in  FIG. 11 , the following procedure was employed. 
     (1) The preparation instrument  100  of  FIG. 1  was prepared. Then, 1.5 ml of 2% L-arginine aqueous solution serving as a dispersed phase, that is, an aqueous phase, was loaded into the space  8 . Then, 1.5 ml of Montanide serving as a continuous phase, that is, an oil phase, was loaded into the space  9 . Here, the syringes  8  and  9  were B BRAUN-fabricated and had a capacity of 5 ml. 
     (2) Pumping operation was manually performed alternately on the plunger  82  of the syringe  8  and the plunger  92  of the syringe  9 . This operation was repeated 5 times. As a result, both phases were accommodated into the syringe  8 . 
     (3) As shown in  FIG. 11 , the preparation instrument  100  was installed in an autograph device  55  (model EZ-L-500N, Shimadzu Corporation) provided with a support base  551  and a load cell  552 . Then, the sliding resistance at the time of alternately pushing the plunger  82  of the syringe  8  and the plunger  92  of the syringe  9  was measured with the load cell  552 . Further, as the resistance, a mean value was calculated for the load during the plunger stroke from 5 to 15 mm. 
     Here, the sliding speed of the plungers  82  and  92  of both syringes  8  and  9  was set at 500 mm/min and 1000 mm/min. 
     [Results] 
     Table 3 shows test results. Each test was performed once for the sliding speed of the plunger  82  of 500 mm/min and performed twice for 1000 mm/min. 
     
       
         
               
               
               
               
               
             
               
               
               
               
               
               
             
               
               
               
               
               
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 3 
               
             
             
               
                   
               
               
                   
                   
                   
                 Sliding 
                   
               
               
                   
                   
                 Sliding 
                 speed 
                   
               
               
                   
                   
                 speed 
                 1000 mm/min 
                   
               
               
                   
                   
                 500 mm/min 
                 Sliding 
                   
               
               
                   
                   
                 Sliding 
                 resistance 
                   
               
               
                   
                 Fibers 
                 resistance 
                 evaluation 
                   
               
             
          
           
               
                   
                 Thickness 
                 Length 
                 evaluation 
                 test A 
                   
               
             
          
           
               
                 Ex. 
                 (denier) 
                 (mm) 
                 test A 
                 First 
                 Second 
               
               
                   
               
             
          
           
               
                 1 
                 50 
                 1000 
                 ∘ 
                 ∘ 
                 x 
               
               
                 2 
                 50 
                 560 
                 ∘ 
                 ∘ 
                 ∘ 
               
               
                 3 
                 50 
                 280 
                 ∘ 
                 ∘ 
                 ∘ 
               
               
                 4 
                 50 
                 140 
                 ∘ 
                 ∘ 
                 ∘ 
               
               
                 5 
                 100 
                 1000 
                 x 
                 ∘ 
                 x 
               
               
                 6 
                 100 
                 560 
                 ∘ 
                 ∘ 
                 ∘ 
               
               
                 7 
                 100 
                 280 
                 ∘ 
                 ∘ 
                 ∘ 
               
               
                 8 
                 100 
                 140 
                 ∘ 
                 ∘ 
                 ∘ 
               
               
                 9 
                 150 
                 560 
                 ∘ 
                 ∘ 
                 ∘ 
               
               
                 10 
                 150 
                 280 
                 ∘ 
                 ∘ 
                 ∘ 
               
               
                 11 
                 150 
                 140 
                 ∘ 
                 ∘ 
                 ∘ 
               
               
                   
               
             
          
         
       
     
     In a case that the pumping operation speed is 500 mm/min, the operability is light and satisfactory when the sliding resistance is lower than 70 N. Thus, this situation is indicated by “∘”. Further, in case of 70 N or higher, this situation is indicated by “x”. Further, in a case that the pumping operation speed is 1000 mm/min, the operability is light and satisfactory when the sliding resistance is lower than 140 N. Thus, this situation is indicated by “∘”. Further, in case of 140 N or higher, this situation is indicated by “x”. 
     As seen from Table 3, in examples 1 to 11, the operability of pumping was satisfactory. 
     (Sliding Resistance Evaluation Test B) 
     [Test Method] 
     As shown in  FIG. 11 , the following procedure was employed. 
     (1) The preparation instrument  100  of  FIG. 1  was prepared. Then, 1.5 ml of 2% L-arginine aqueous solution serving as a dispersed phase, that is, an aqueous phase, was loaded into the space  8 . Then, 1.5 ml of Montanide serving as a continuous phase, that is, an oil phase, was loaded into the space  9 . Here, the syringes  8  and  9  were B BRAUN-fabricated and had a capacity of 5 ml. 
     (2) Pumping operation was manually performed alternately on the plunger  82  of the syringe  8  and the plunger  92  of the syringe  9 . This operation was repeated 5 times. As a result, both phases were accommodated into the syringe  8 . 
     (3) As shown in  FIG. 11 , the preparation instrument  100  was installed in an autograph device  55  (model AG-500BR, Shimadzu Corporation) provided with a support base  551  and a load cell  552 . Then, the sliding resistance at the time of alternately pushing the plunger  82  of the syringe  8  and the plunger  92  of the syringe  9  was measured with the load cell  552 . The resistance was measured at the first time, the second time, and the third time of pumping operation. Further, as the resistance, a mean value was calculated for the load during the plunger stroke from 5 to 15 mm. The sliding speed was set at 500 mm/min. 
     [Results] 
     
       
         
               
               
             
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
               
               
               
             
           
               
                 TABLE 4 
               
             
             
               
                   
               
               
                   
                 Sliding resistance (N) 
               
             
          
           
               
                   
                 Mesh 
                 First pumping 
                 Second pumping 
                 Third pumping 
                   
                 Standard 
               
             
          
           
               
                 Ex. 
                 part 
                 Syr. 8 
                 Syr. 9 
                 Syr. 8 
                 Syr. 9 
                 Syr. 8 
                 Syr. 9 
                 Average 
                 Deviation 
               
               
                   
               
             
          
           
               
                 12 
                 FIG. 3 
                 20.23 
                 19.51 
                 18.50 
                 20.07 
                 20.79 
                 21.17 
                 20.05 
                 0.95 
               
               
                 13 
                 FIG. 8 
                 21.71 
                 23.01 
                 23.89 
                 25.75 
                   
                   
                 23.59 
                 1.70 
               
               
                 14 
                 FIG. 9 
                 33.08 
                 30.39 
                 26.91 
                 27.37 
                   
                   
                 29.44 
                 2.88 
               
               
                   
               
             
          
         
       
     
     As seen from Table 4, in examples 12, 13, and 14, the sliding resistance was lower than the conventional art. Thus, the operability was satisfactory. In particular, in example 12, that is, in a case that the mesh part having the configuration of  FIG. 3  was employed, the sliding resistance was the lowest. Thus, in a case that the mesh part having the configuration of  FIG. 3  was employed, the operability was the most satisfactory. 
     (Sliding Resistance Evaluation Test C) 
     [Test Method] 
     As shown in  FIG. 11 , the following procedure was employed. 
     (1) The preparation instrument  100  of  FIG. 1  was prepared in example 12 and the preparation instrument  100  of  FIG. 4  was prepared in example 15. Then, 1.5 ml of physiological saline serving as a dispersed phase, that is, an aqueous phase, was loaded into the syringe  8 . Then, 1.5 ml of Montanide serving as a continuous phase, that is, an oil phase, was loaded into the space  9 . Here, the syringes  8  and  9  were B BRAUN-fabricated and had a capacity of 5 ml. 
     (2) Pumping operation was manually performed alternately on the plunger  82  of the syringe  8  and the plunger  92  of the syringe  9 . This operation was repeated 5 times. As a result, both phases were accommodated into the syringe  8 . 
     (3) As shown in  FIG. 11 , the preparation instrument  100  was installed in an autograph device  55  (model AG-Xplus, Shimadzu Corporation) provided with a support base  551  and a load cell  552 . Then, the sliding resistance at the time of alternately pushing the plunger  82  of the syringe  8  and the plunger  92  of the syringe  9  was measured with the load cell  552 . The resistance was measured at the first time, the second time, and the third time of pumping operation. Further, as the resistance, a mean value was calculated for the load during the plunger stroke from 5 to 15 mm. The sliding speed was set at 500 mm/min. 
     [Results] 
     Table 5 shows test results. 
     
       
         
               
               
             
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
               
               
               
             
           
               
                 TABLE 5 
               
             
             
               
                   
               
               
                   
                 Sliding resistance (N) 
               
             
          
           
               
                   
                 Mesh 
                 First pumping 
                 Second pumping 
                 Third pumping 
                   
                 Standard 
               
             
          
           
               
                 Ex. 
                 part 
                 Syr. 8 
                 Syr. 9 
                 Syr. 8 
                 Syr. 9 
                 Syr. 8 
                 Syr. 9 
                 Average 
                 Deviation 
               
               
                   
               
             
          
           
               
                 12 
                 FIG. 3 
                 23.32 
                 22.57 
                 21.25 
                 34.50 
                 21.20 
                 21.63 
                 24.08 
                 4.72 
               
               
                 15 
                 FIG. 3 
                 22.69 
                 27.98 
                 25.38 
                 25.70 
                 22.48 
                 22.93 
                 24.53 
                 2.01 
               
               
                   
               
             
          
         
       
     
     As seen from Table 5, in examples 12 and 15, the sliding resistance was lower than the conventional art. Thus, the operability was satisfactory. 
     (Foreign Substance Evaluation Test) 
     [Test Method] 
     (1)  FIG. 12  shows the situation of the test concerning the device  1  of example 12. Here, in example 15, the device  1 A was employed in place of the device  1 . A glass syringe  62  was attached through a 0.8-μm membrane filter  61  to one end of the device  1 . Then, 10 ml of particulate-free deionized water was vigorously ejected through the filter  61  and the device  1  into a clean glass bottle  63 . This operation was performed five times in total. Then, the filter  61  and the syringe  62  were removed and then attached to the other end of the device  1  similarly, and then the same operation was performed. By virtue of this, approximately 100 ml of deionized water was collected in the glass bottle  63 . This deionized water was employed as the sample. 
     (2) Japanese Pharmacopoeia Sixteenth Edition “Insoluble Particulate Matter Test for Injections, Method  1 . Light Obscuration Particle Count Test” was performed on the sample. Specifically, insoluble particulates per 10 ml of the sample were measured four times with an in-liquid particulate measurement instrument (product name: RION KL-04). Then, the second to the fourth measurement values were converted into the number of particulates per vessel. This measurement was performed five times in total with changing the sample. 
     [Results] 
     Table 6 shows the results of example 12. Table 7 shows the results of example 15. 
     
       
         
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE 6 
               
               
                   
               
               
                 Partic. 
                   
                   
                   
                   
                   
                   
               
               
                 Size (μm) 
                 First 
                 Second 
                 Third 
                 Fourth 
                 Fifth 
                 Average 
               
               
                   
               
             
             
               
                   
               
             
          
           
               
                   1.3≦ 
                 88 
                 137 
                 73 
                 64 
                 71 
                 87 
               
               
                  2≦ 
                 45 
                 74 
                 37 
                 35 
                 36 
                 45 
               
               
                  5≦ 
                 24 
                 27 
                 16 
                 14 
                 12 
                 19 
               
               
                 10≦ 
                 15 
                 14 
                 11 
                 4 
                 5 
                 10 
               
               
                 15≦ 
                 5 
                 4 
                 4 
                 1 
                 2 
                 3 
               
               
                 25≦ 
                 0 
                 0 
                 0 
                 0 
                 0 
                 0 
               
               
                 50≦ 
                 0 
                 0 
                 0 
                 0 
                 0 
                 0 
               
               
                 100≦  
                 0 
                 0 
                 0 
                 0 
                 0 
                 0 
               
               
                   
               
             
          
         
       
     
     
       
         
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE 7 
               
               
                   
               
               
                 Partic. 
                   
                   
                   
                   
                   
                   
               
               
                 Size (μm) 
                 First 
                 Second 
                 Third 
                 Fourth 
                 Fifth 
                 Average 
               
               
                   
               
             
             
               
                   
               
             
          
           
               
                   1.3≦ 
                 980 
                 108 
                 155 
                 210 
                 108 
                 136 
               
               
                  2≦ 
                 500 
                 47 
                 85 
                 74 
                 65 
                 64 
               
               
                  5≦ 
                 200 
                 15 
                 39 
                 23 
                 21 
                 24 
               
               
                 10≦ 
                 80 
                 8 
                 18 
                 6 
                 2 
                 8 
               
               
                 15≦ 
                 30 
                 4 
                 3 
                 1 
                 0 
                 2 
               
               
                 25≦ 
                 0 
                 0 
                 0 
                 0 
                 0 
                 0 
               
               
                 50≦ 
                 0 
                 0 
                 0 
                 0 
                 0 
                 0 
               
               
                 100≦  
                 0 
                 0 
                 0 
                 0 
                 0 
                 0 
               
               
                   
               
             
          
         
       
     
     With reference to a test method “B. Solutions for injection supplied in containers with a nominal content of less than 100 ml” in the above-mentioned Japanese Pharmacopoeia, the allowance criterion for the average number of particulates is “6000 or fewer for particulates of 10 μm or larger and 600 or fewer for particulates of 25 μm or larger, per vessel”. However, in the present test, a ten-fold severer allowance criterion was employed that “600 or fewer for particulates of 10 μm or larger and 60 or fewer for particulates of 25 μm or larger, per vessel”. 
     In both of examples 12 and 15, the severer allowance criterion has been satisfied. Thus, both devices  1  and  1 A are excellent in the foreign substance quality and hence have sufficient cleanliness for the use as medical equipment. 
     INDUSTRIAL APPLICABILITY 
     The emulsion preparation device of the present invention can form an emulsion for a chemical liquid of diverse composition, further can realize a relatively low sliding resistance, and hence has a great advantage in industrial utilization. 
     DESCRIPTION OF REFERENCE NUMERALS 
       1 :  1 A Device,  10 : Filter part,  100 : Preparation instrument,  2 : First cylindrical member,  21 : First cylinder part,  211 : Aperture periphery,  22 : Second cylinder cart,  23 : Concave lid,  231 : Outer flange,  28 : Luer taper,  31 : First mesh part,  311 : Through hole,  32 : Fibers,  33 : Second mesh part,  4 : Second cylindrical member,  29 ,  49 : Outer flange,  8 ,  9 : Syringe

Technology Category: 7