Abstract:
A spray head ( 30 ) for an applicator ( 1 ) for applying biological tissue bonding agent to an affected area, where the bonding agent is produced by spraying and mixing solutions respectively received in a pair of syringes ( 2  ( 2   a,    2   b )). The spray head ( 30 ) has a first nozzle opening ( 42   a ) from which the solution received in either one ( 2   a ) of the syringes is jetted in a predetermined jetting direction, and also has a second nozzle opening ( 42   b ) from which the solution received in the other syringe ( 2   b ) is jetted in the direction same as or substantially the same as the predetermined jetting direction. The second nozzle opening ( 42   b ) is placed forward in the jetting direction from the first nozzle opening ( 42   a ). In applying the biological tissue bonding agent, which is formed by simultaneously spraying the first solution received in the first syringe and the second solution received in the second syringe and mixing them together, onto an affected area, a clogging of the nozzle openings from which the first and second solutions are jetted can be prevented, and as a result, intermittent application of the bonding agent can be reliably performed.

Description:
FIELD OF THE INVENTION 
       [0001]    The present invention relates to an apparatus for applying a biological tissue adhesive to surgical sites, the adhesive being obtained by simultaneously spraying and mixing a first solution containing a first component such as animal protein and a second solution containing a second component for accelerating coagulation reaction of the first component. Also, the present invention relates to a spray head for use with the apparatus. Further, the present invention relates to a method for applying a adhesive such as biological tissue adhesive. 
       BACKGROUND OF THE INVENTION 
       [0002]    Conventionally, the biological tissue adhesive containing animal protein in its major proportion is produced in clinical practices by mixing one solution (first solution) containing fibrinogen with the other solution (second solution) containing thrombin. 
         [0003]    In order for the biological tissue adhesive to be readily and effectively used in clinical practices, a variety of techniques in each of which the first solution accommodated in the first syringe and the second solution accommodated in the second syringe are simultaneously ejected therefrom respectively and mixed with each other to apply the mixture on the surgical sites are disclosed in, among others, JP 64-25843 A, JP 64-40040 A, JUM 3-181979 B, JP 2741323 B, JP 2837099 B, JP 8-281150 A, and JP 11-76245 A. The applicant developed a biological tissue adhesive applicator for spraying the first and second solutions and thereby mixing the sprayed solutions with each other. This applicator is disclosed in JP 2555549 B and has been provided to the practical clinical sites. Through the developments and services of the applicator, the biological tissue adhesive has been widely used as adhesive or hemostatic agent in various medical areas. 
         [0004]    In such applicators, the first and second solutions are accommodated in respective syringes independently to prevent them from making contacts or mixing with each other, which eventually prevents any generation of coagulation which may otherwise be caused by the mixing of two solutions or the resultant plugging of the ejections ports of the solutions. Practically, however, the intermittent ejections of the solutions may cause coagulation in the vicinities of the ejection ports (in particular, the ejection port for the first solution containing fibrinogen), by the mixing of the solutions remaining adjacent the ports. It can be understood that the coagulation reaction is caused by air flow formed around the ports at the ejection of the solutions, dripping of the solutions caused after the ejections, and/or bouncing of the solutions from the surgical sites. The coagulation so caused may plug the ejection port or ports to prevent subsequent ejections of the solutions. 
         [0005]    Accordingly, the present invention is to provide an improvement to the technology in which the first solution accommodated in the first syringe and the second solution accommodated in the second syringe are simultaneously sprayed and mixed with each other, wherein the improvement prevents the ejection port or ports from being plugged by the mixture of the solutions and allows the intermittent applications of the biological tissue adhesive. 
       SUMMARY OF THE INVENTION 
       [0006]    To this end, a spray head according to the invention is for use with a biological tissue adhesive applicator for spraying and mixing solutions accommodated in a pair of syringes respectively to obtain a biological tissue adhesive to be applied to surgical sites and comprises a first ejection port for ejecting the solution accommodated in one syringe in a predetermined ejecting direction; and a second ejection port for ejecting the solution accommodated in the other syringe in a direction which is the same or substantially the same as said ejecting direction, the second ejection port being disposed forward of said first ejection port. 
         [0007]    A method for spraying and mixing a first solution and a second solution accelerating a coagulation reaction of the first solution, according to the invention comprises ejecting the first solution from a first ejection port, and ejecting said second solution from a second solution port, the second ejection port being disposed forward of the first ejection port with respect to a direction in which the first solution is ejected from the first ejection port. 
         [0008]    With the invention, the arrangement that the second ejection port is disposed forward of the first ejection port with respect to the ejecting direction prevents the first and second solutions from being mixed with each other and, as a result, a plugging of the fist ejection port by any coagulation which would otherwise be caused by the mixing of the solutions when the first and second solutions are ejected from respective ejection ports. Also, the plugging of the second port is prevented by the fact that one solution containing a first component (fibrinogen solution, for example) is used for the first solution and the other solution containing a second component capable of accelerating a coagulation reaction of the first component (thrombin solution, for example) is used for the second solution in order to prohibit an active coagulation reaction even if a small amount of first solution were mixed in the second solution. Therefore, according to the invention, no plugging occurs at the first or second ejection port, which ensures the intermittent applications of the adhesive. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0009]      FIG. 1  is an exploded perspective view of a biological tissue adhesive applicator according to a first embodiment; 
           [0010]      FIG. 2  is a plan view of the assembled applicator shown in  FIG. 1 ; 
           [0011]      FIG. 3  is a side elevation of the assembled applicator shown in  FIG. 1 ; 
           [0012]      FIG. 4  is a horizontal cross section of a spray head according to a first embodiment of  FIG. 1 ; 
           [0013]      FIG. 5  is a vertical cross section of the spray head shown in  FIG. 4 ; 
           [0014]      FIG. 6  is an exploded perspective view of a biological tissue adhesive applicator according to a second embodiment; 
           [0015]      FIG. 7  is a plan view of the assembled applicator shown in  FIG. 6 ; 
           [0016]      FIG. 8  is a vertical cross section of a spray head according to the second embodiment; 
           [0017]      FIG. 9  is a horizontal cross section of the spray head shown in  FIG. 8 ; 
           [0018]      FIG. 10  is an exploded perspective view of a conventional applicator used in experiments  3  and  5 ; 
           [0019]      FIG. 11  is an exploded perspective view of an applicator according to the invention, which is used in experiments  2 ,  3 , and  5 ; and 
           [0020]      FIG. 12  is an exploded perspective view of an applicator according to the invention, which is used in experiment 4. 
       
    
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS 
       [0021]    Hereinafter, preferred embodiments of the present invention will be described with reference to the accompanying drawings. In the following description, terminologies referring to specific directions (for example, “up”, “down”, “left”, “right”, and others including these terminologies) will be used. It should be noted that these terms are used for the purpose of facilitating the understanding of the invention taken in conjunction with the drawings and meanings of these terms should not be construed as restricting the present invention. 
         [0022]    Referring now to  FIGS. 1-5 , a first embodiment of the present invention will be described. As shown in  FIGS. 1-3 , a biological tissue adhesive applicator, generally indicated by reference numeral  1 , according to the first embodiment of the invention has a first syringe  2   a  for accommodating fibrinogen solution (first solution) including fibrinogen (first component) and a second syringe  2   b  for accommodating thrombin solution (second solution) including thrombin (second component) capable of accelerating the coagulation reaction of fibrinogen, and a spray head  30  for spraying the fibrinogen and thrombin solutions supplied from the syringes  2  ( 2   a ,  2   b ), respectively. 
         [0023]    Each syringe  2  has a barrel  3  and a plunger  7 . The barrel  3  has a cylindrical body  4 , a nozzle  5  at one end of the cylindrical body  4 , and flanges  6  at the other end of the cylindrical body  4  and extending radially outwardly, formed integrally therewith. The plunger  7  has a gasket made of rubber for example and mounted at one end thereof, having a diameter slightly larger than the inner diameter of the cylindrical body, and a thumb yoke  9  integrally made therewith. The one end of the plunger  7  carrying the gasket  8  is inserted in the interior of the cylindrical body  4  of the barrel  3  so that the gasket  8  makes a sealing contact with the inner peripheral surface of the cylindrical body  4 . The plungers  7  may have different colors so that users can readily identify the solutions accommodated in respective syringes  2 . For example, one plunger for the syringe  2   a  accommodating the fibrinogen solution is blue-colored and the other plunger for the syringe  2   b  accommodating the thrombin solution is red-colored. 
         [0024]    The two barrels  3  are held by a syringe holding member or holder  10 . The holder  10  is integrally formed of synthetic resin such as polyethylene, polypropylene, or acrylonitrile-butadiene-styrene copolymer and has two grooves  11  extending in parallel to each other. Each groove  11  has a C-shaped inner surface which substantially corresponds to the outer configuration of the cylindrical body  4 . A transverse width of the top opening of the groove  11  is smaller than the outer diameter of the cylindrical body  4 , which allows the holder  10  to securely hold the barrel  3  in the groove  11  when the barrel  3  is fitted in the groove  11 . 
         [0025]    The holder  10  has a stop  14  opposing a rear end of the connecting portion  12  positioned between the grooves  11  while leaving a certain gap therebetween and stops  16  opposing respective rear ends of the outward walls  13  defining in part the grooves  11 . The stops  14  and  16  cooperate with the rear end surfaces  18  opposing thereto to define a pair of flange receiving grooves  20  so that, when the barrels  3  are fitted in respective grooves  11 , the flanges  6  of the barrels  3  are also fitted in respective grooves  20 . 
         [0026]    The plungers  7  inserted in respective barrels  3  are simultaneously actuated by the use of an actuator  22 . The actuator  22 , which is preferably made of the same material as that of holder  10 , has a front wall  24  and a rear wall  26  opposing the front wall  24  while leaving a certain gap therebetween. Preferably, the gap between the front and rear walls  24  and  26  is determined to be substantially the same as the thickness of the thumb yoke  9  of the plunger  7 . The front wall  24  has two upwardly-opened cutouts  28  in the form “U”, for example. A distance between the centers of the cutouts  28  is determined to be the same as that of the grooves  11 . 
         [0027]    As shown in  FIGS. 4 and 5 , the spray head  30  has a flattened hollow housing  32 . The housing  32  has a pair of first and second gas ejection nozzles  34  ( 34   a ,  34   b ) each defined by the cylindrical walls at the front end of the housing  32 . The interiors of the gas ejection nozzles  34  are connected with the interior of the housing  32 . The gas ejection nozzles  34   a  and  34   b  are so disposed that the longitudinal axes of the nozzles orient in the same or substantially the same ejecting direction. 
         [0028]    The second gas ejection nozzle  34   b  is disposed forward of the first gas ejection nozzle  34   a  with respect to the ejecting direction. The outer peripheries of the gas ejection nozzles  34   a ,  34   b  are spaced apart from each other to define a recess  44  extending in the rearward direction. The spaced-apart arrangement of the nozzles  34   a ,  34   b  prevents the solution possibly staying at the distal end of one gas ejection nozzle  34  from moving along the outer peripheral surface of its gas ejection nozzle to meet the other solution possibly staying at the distal end of the other gas ejection nozzle  34 . It is not necessary for the peripheral surfaces of gas ejection nozzles  34   a ,  34   b  are transversely spaced apart from each other. Alternatively, at least the distal end peripheral portion of the first gas ejection nozzle  34   a  may be spaced apart from the peripheral surface of the second gas ejection nozzle  34   b.    
         [0029]    Each of the gas ejection nozzles  34  has a plurality of ribs  35  formed therewith and extending radially inwardly to define a space surrounded by the ribs  35  in which a solution tube  40  is inserted. 
         [0030]    The housing  32  has a pair of syringe connectors  38  ( 38   a ,  38   b ) formed therewith at the rear end thereof. The syringe connectors  38   a ,  38   b  receive first and second adaptors  36   a ,  36   b  engaged therein respectively for receiving the nozzles  5  of the first and second syringes  2   a ,  2   b  fitted therein. Preferably, the syringe connectors  38  are colored in respective colors which are different from each other but the same as those of the corresponding plungers  7  of the syringes  2 , which allows users to identify the syringes  2  to be connected to respective syringe connectors  38  at the assembling of the syringes  2  to the spray head  30 . For example, the syringe connector  38   a  is blue-colored corresponding to the first syringe  2   a  and the syringe connector  38   b  is red-colored corresponding to the second syringe  2   b . The adaptors  36  ( 36   a ,  36   b ) are tapered forwardly so that the nozzles  5  of the syringes  2  are well fitted therein. Also, the adaptors  36  have distal end openings defined therewith. 
         [0031]    First and second solution tubes  40  ( 40   a ,  40   b ) are disposed within the interior of the housing  32 . One end of the solution tube  40   a  is connected to the distal end opening of the first adaptor  36   a  and the other end thereof is inserted in the first gas ejection nozzle  34   a . One end of the second solution tube  40   b  is connected to the distal end opening of the second adaptor  36   b  and the other end thereof is inserted in the second gas ejection nozzle  34   b . The other ends of the solution tubes  40  are projected a certain distance from the gas ejection nozzles  34 , which results in that the distal end of the first solution tube  40   a  defines a first ejection nozzle  42   a  for ejecting the fibrinogen solution and the distal end of the second solution tube  40   b  defines a second ejection nozzle  42   b  for ejecting the thrombin solution. Preferably, the projected length of the tubes  40  are 0.1-10 mm, for example, which ensures that the solutions being ejected from the tubes  40  are uniformly sprayed with an aid of sterile gas ejected from the gas ejection nozzles  34 . 
         [0032]    A distance between the longitudinal central axes of the ejection nozzles  42   a ,  42   b  is set preferably in the range of 2-10 mm, or more preferably in the range of 3-6 mm. It should be noted that those ranges are not restrictive to the present invention and may be larger or smaller if the directions along which the solutions are ejected are nonparallel to each other due to, for example, inclinations of the solution tubes  42   a ,  42   b . The ejection nozzles  42   a ,  42   b  take different positions with respect to the ejecting direction so that the second ejection nozzle  42   b  is disposed forward of the first ejection nozzle  42   a  with respect to the direction. The distance between the ejection nozzles  42   a ,  42   b  with respect to the ejecting direction is determined by taking account of the transverse distance of the nozzles and spraying angle of the solution from the rearward first ejection nozzle  42   a  so that the ejected solution from the first ejection nozzle  42   a  does not make contact with the forward second ejection nozzle  42   b . The distance is set preferably in the range of 5-16 mm, or more preferably in the range of 6-8 mm, which are not restrictive to the invention. 
         [0033]    The spray head  30  also has a gas supply tube extending downwardly and rearwardly from the bottom wall thereof. Although the gas supply tube  46  is integrally formed with the housing  32 , it may be manufactured independently and connected to the bottom wall of the housing  32 . Although not shown, during the operation of the applicator  1 , the gas supply tube  46  is connected to a gas supply source through a filter so that a gas is sterilized by the filter and then supplied through the gas supply tube  46  into the interior of the housing  32 . A filter unit commercially available from Millipore under the trade name Millex FG is preferably used for the filter. 
         [0034]    Before using the applicator  1  so constructed, a certain amount of fibrinogen solution is accommodated in the first syringe  2   a  and the same amount of, for example, thrombin solution is accommodated in the second syringe  2   b.    
         [0035]    Then, the barrels  3  of the syringes  2  are fitted in respective grooves  11  of the holder  10  and the flanges  6  of the barrels  3  are also fitted in the flange receiving grooves  20 . The transverse widths of the top openings of the grooves  11  are larger than the outer diameter of the barrels so that the barrels  3  are well retained by the holder  3  without dropping therefrom. 
         [0036]    Also, the thumb yokes  9  of the plungers  7  are fitted between the front and rear walls  24  and  26  of the actuator  22  and the rear end portions of the plungers  7  adjacent the thumb yokes  9  are fitted in the cutouts  28  of the front wall  24 . Since the gap between the front and rear walls  24  and  26  is substantially the same as the thickness of the thumb yokes  9 , the actuator  22  is well retained on the plungers  7 . 
         [0037]    Further, the nozzle  5  of the first syringe  2   a  accommodating the fibrinogen solution is fitted in the first adaptor  36   a  of the spray head  30  and the nozzle  5  of the second syringe  2   b  accommodating the thrombin solution is fitted in the second adaptor  36   b  of the spray head  30 . 
         [0038]    Furthermore, the gas supply tube  46  of the spray head  30  is connected through the filter to a tube extending from the gas supply not shown. 
         [0039]    When using the applicator  1  so assembled, the sterile gas is supplied into the interior of the housing  32  of the spray head  30  through the gas supply tube  46  from the gas supply and then ejected from the gas ejection nozzles  34 . 
         [0040]    An operator places his or her index and/or mid finger on the holder  10  and/or flange  6  and thumb finger on the rear surface of the actuator  22  and forces the plungers  7  into respective barrels  3 , which causes the solutions to be ejected from the solution tubes  40 . The solutions ejected from respective tubes  40  are sprayed with an aid the sterile gas ejected therearound and then the sprayed solutions are mixed with each other and applied on the surgical sites. The tubes  40  inserted in respective gas ejection nozzles  34  are retained in a stable manner by the ribs  35  disposed therearound, so that the solutions from the nozzles  42  ( 42   a ,  42   b ) of the tubes  40  are sprayed in the predetermined directions, which ensures the mixtures to be applied to the target sites. 
         [0041]    In particular, the second ejection nozzle  42   b  is placed forward of the first ejection nozzle  42   a  with respect to the ejecting direction. This prevents the thrombin solution from the second ejection nozzle  42   b  from making contacts with the fibrinogen solution in the vicinity of the first ejection nozzle  42   a  to generate any coagulation which may plug the first ejection nozzle  42   a.    
         [0042]    As described above, the longitudinal distance between the first and second ejection nozzles  42  is so determined as to prevent the fibrinogen solution ejected from the first ejection nozzle  42   a  from making contacts with the second ejection nozzle  42   b . However, it may occur that, due to the air flow generated at the ejections of the solutions, only a small amount of fibrinogen solution ejected from the first ejection nozzle  42   a  adheres to the second ejection nozzle  42   b  to mix with the thrombin solution. In this instance, however, even if mixed in the thrombin solution, this small amount of fibrinogen solution does not drive an active chemical reaction with the thrombin solution to cause unwanted plugging of the second ejection nozzle  42   b.    
         [0043]    As described above, according to the spray head  30 , no plugging occurs at the first and/or the second ejection nozzle  42   a ,  42   b , which ensures the intermittent application of the biological tissue adhesive. 
         [0044]    Also, the larger gap defined between the spaced apart gas ejection nozzles  34   a ,  34   b  effectively reduces the possibility that the solution remaining at one ejection nozzle  34  moves along the peripheries of the nozzles to reach the other ejection nozzle  34  and then mixes with the other solution during the time periods between the ejecting operations. 
         [0045]    The housing  32  of the spray head  30  may be provided with a forward extension at its front end having a length of 5-50 cm, for example. In this modification, the distal end of the extension may be formed with a pair of gas ejection nozzles as described above. This allows the solutions to be sprayed uniformly in the deep portions of living bodies. 
         [0046]    Also, a gun-type applicator disclosed in JP 2555549 B, for example, may be combined with the biological tissue adhesive applicator  1 . 
         [0047]    Referring next to  FIGS. 6-9 , a second embodiment of the present invention will be described below. As shown in  FIGS. 6 and 7 , similar to the first embodiment of the invention, the biological tissue adhesive applicator  51  according to the second embodiment of the invention has a first syringe  2   a  for accommodating fibrinogen solution, a second syringe  2   b  accommodating thrombin solution, and a spray head  80  for spraying the fibrinogen and thrombin solutions from respective syringes. The detailed structures of the syringes are the same as those of the first embodiment. 
         [0048]    Similar to the first embodiment, the applicator  51  has a holder  60  for integrally holding two barrels  3 . Also similar to the first embodiment, the holder  60  has two grooves  11  defined therewith. According to the embodiment, the grooves  11  have different longitudinal lengths. Specifically, the rear end portion  68  for one groove  11  is displaced rearward of the rear end portion  69  for the other groove  11 . The stops  64 ,  66  are provided to oppose the rear end portions  68 ,  69  leaving a gap to form the flange receiving grooves  70 ,  71  for receiving the flanges  6  of the barrels  3  fitted in the grooves  11 , respectively. The arrangement of the flange receiving grooves  70 ,  71  displaced from each other in the longitudinal direction of the grooves  11  allows the holder  60  to hold the barrels  3  in a displaced manner. 
         [0049]    The actuator  72  for simultaneously activating the plungers  7  inserted in respective barrels  3  has two front walls  74 ,  75  and two rear walls  76 ,  77 . The front walls  74 ,  75  are displaced from each other in the longitudinal direction corresponding to the displacement of the grooves  70 ,  71 . Likewise, the rear walls  76 ,  77  are displaced from each other in the longitudinal direction. The front wall  74 ,  75  have cutouts  78  opened upwardly, in the form of “U”. The distance between the centers of the cutouts  78  is the same as that of grooves  11  of the holder  60 . 
         [0050]    The spray head  80  has a first hollow housing  82   a  to be attached to the first syringe  2   a , a second hollow housing  82   b  to be attached to the second syringe  2   b , a first gas ejection nozzle  34   a  connected to the first housing  82   a  through a connection pipe  89 , and a second gas ejection nozzle  34   b  connected to the second housing  82   b  through a connection pipe  89 . In this arrangement, an interior of the first gas ejection nozzle  34   a  is connected to that of the first housing  82   a  and an interior of the second gas ejection nozzle  34   b  is connected to that of the second housing  82   b . It should be noted that the gas ejection nozzles  34  ( 34   a ,  34   b ) may be directly connected to respective housings  82  ( 82   a ,  82   b ) without using connection pipes  89 . 
         [0051]    As shown in  FIGS. 8 and 9 , the first housing  82   a  receives a first adaptor  36   a  mounted therein and the second housing  82   b  has a second adaptor  36   b  mounted therein. Preferably, the housings  82  ( 82   a ,  82   b ) are colored in the same colors as the associated plungers  8 , respectively, so that operators can see easily which syringe  2  should be connected to which housing  82  at the assembling of the syringes  2  to the associated spray heads  80 . For example, the first housing  82   a  is blue-colored as the first syringe  2   a  and the second housing  82   b  is red-colored as the second syringe  2   b.    
         [0052]    Each of the gas ejection nozzles  34  has a cylindrical wall which bears a plurality of flanges  86  ( 86   a ,  86   b ,  86   c ,  86   d ) extending outwardly therefrom. The flanges  86  are disposed at certain intervals in the ejecting direction. For example, the flanges  86   a ,  86   d  are so arranged that the distance from the first flange  86   a  to the second flange  86   b  is the same as that from the third flange  86   c  to the fourth flange  86   d.    
         [0053]    The first and second gas ejection nozzles  34   a ,  34   b  are retained by the nozzle holder  90 . As shown in  FIG. 6 , the nozzle holder  90  has a pair of grooves  91  extending in parallel to each other. Each groove  91  has a C-shaped inner surface portion which substantially corresponds to the outer peripheral surface portion of the gas ejection nozzle  34 . The transverse width of the top opening of the grooves  91  is smaller than the outer diameter of the gas ejection nozzle  34  so that, when the gas ejection nozzles are fitted in the respective grooves  91 , they are securely retained by the nozzle holder  90 . The longitudinal axes of the gas ejection nozzles  34   a ,  34   b  are directed to the same or substantially the same direction in which the solutions are ejected. The longitudinal length of the grooves  91  is substantially the same as the lengths of the portions of the nozzles existing between the neighboring flanges  86 , which ensures to prevent any displacement in the ejecting direction of the gas ejection nozzles  34  fitted in the grooves  91 . This means that, simply by fitting the gas ejection nozzles in the nozzle holder  90 , the relative positional relation between the gas ejection nozzles  34  is determined. As shown in  FIGS. 8 and 9 , in this embodiment a portion of the first ejection nozzle  34   a  between the first and second flanges  86   a ,  86   b  is fitted in one groove  91  and a portion of the second ejection nozzle  34   b  between the third and fourth flanges  86   c ,  86   d  is fitted in the other groove  91 , which ensures that the gas ejection nozzles  34  are positioned properly to meet the predetermined positional relation thereof in which the second ejection nozzle  34   b  is disposed forward of the first gas ejection nozzle  34   a  in the gas ejecting direction. 
         [0054]    The connection tubes  89  are connected at one ends thereof to the distal end openings of the housings  82   a ,  82   b  and at the other ends thereof to the gas ejection nozzles  34 , respectively. A first solution tube  40   a  is inserted in the connection tube  89  connected to the first housing  82   a  and a second solution tube  40   b  is inserted in the connection tube  89  connected to the second housing  82   b . Preferably, the connection tubes  89  are made of flexible material. 
         [0055]    Similar to the first embodiment, one end of each solution tube  40  ( 40   a ,  40   b ) is connected to the distal end opening of the adaptor  36  and the other end thereof is inserted in the gas ejection nozzle  34  and projected a predetermined length from the gas ejection nozzle  34  to terminate at its ejection port  42 . The two ejection ports are disposed to meet the positional relationship as described above simply by fitting the gas ejection nozzles  34  in the nozzle holder  90 . 
         [0056]    Each housing  82  has a gas supply tube  46  as described in the first embodiment. In this embodiment, the gas supply tube  46  is extended from the bottom wall of the housing in the downward and rearward direction. The gas supply tube  46  may be manufactured independently. 
         [0057]    When using the applicator  51  so constructed, similar to the first embodiment, the fibrinogen solution is accommodated in the first syringe  2   a  and the thrombin solution is accommodated in the second syringe  2   b , having the same amount as the fibrinogen solution, for example. Also, the barrels  3  of the syringes  2  are fitted in the holder  60 . Further, the thumb yokes  9  of the plungers  7  are fitted in the actuator  72 . 
         [0058]    Next, the nozzles  5  of the syringes  2   a ,  2   b  are fitted in the associated adaptors  36   a ,  36   b , respectively, and the predetermined portions of the gas ejection nozzles  34   a ,  34   b  are mounted on the nozzle holder  90 . 
         [0059]    Subsequently, the gas supply tube  46  of the spray head  80  is connected through the filter to a tube extending from the gas supply not shown. This allows that the biological tissue adhesive to be applied as described in the first embodiment. 
         [0060]    In the application of the adhesive using the applicator  51 , since the second ejection port  42   b  is disposed forward of the second ejection port  42   b  with respect to the ejecting direction similar to the first embodiment, no plugging occurs at the first or second ejection port  42   a ,  42   b , which allows the applicator  51  to apply the biological tissue adhesive on and off. 
         [0061]    In the second embodiment, other structures and the advantages derived therefrom are the same as those of the first embodiment, and like parts are indicated like reference numerals in  FIGS. 6-9 . 
         [0062]    The structure for displacing the positions of the ejection ports  42   a ,  42   b  with respect to the ejecting direction is not limited to that in which the syringes  2   a ,  2   b  are displaced from each other. For example, the second ejection port  42   b  is displaced forward of the first ejection port  42   a  by shortening the length of the first solution tube  40   a  than the second solution tube  40   b  and also shortening the length of the connection tube  89  inserted in the first solution tube  40   a  than the connection tube  89  inserted in the second solution tube  40   b . Alternatively, the second ejection port  42   b  is displaced forward of the first ejection port  42   a  by sagging the first solution tube  40   a  and the connection tube  89  inserted in the first solution tube  40   a , both made of flexible materials. 
         [0063]    Although the flanges  86  are provided on the gas ejection nozzles  34  in the second embodiment, they may be removed therefrom. In this modification, the second ejection port  42   b  may be placed forward of the first ejection port  42   a  by sliding at least one gas ejection nozzle away from the other after the mounting of the gas ejection nozzles  34   a ,  34   b  on the nozzle holder  90 . 
         [0064]    Although the present invention has been fully described with the specific embodiments thereof, it is not limited thereto. For example, although in the previous embodiments the fibrinogen solution is ejected from the first ejection port  42  and the thrombin solution is ejected from the second ejection port  42   b , the invention can be applied equally to other applicators in which solutions other than fibrinogen and/or thrombin solution is ejected therefrom. 
       Experiment 1 
       [0065]    An experiment was conducted to verify the occurrence of coagulation. In the first test, the thrombin solution was mixed in the fibrinogen solution. In the second test, the fibrinogen solution was mixed in the thrombin solution. 
         [0066]    In the fist test, 1 milliliter of thrombin solution was added in the vial accommodating 3 milliliter of fibrinogen solution and, after a lapse of 10 minutes, the mixture was visually observed. In the second test, 1 milliliter of fibrinogen solution was added in the vial accommodating 3 milliliter of thrombin solution and, after a lapse of 10 minutes, the mixture was visually observed. 
         [0067]    The results showed that the mixture of the first test was wholly coagulated and the mixture of the second test was partially coagulated and the amount of coagulation associated with the amount of fibrinogen added. 
         [0068]    This shows that, by disposing the ejection port of the fibrinogen solution forward of that of thrombin solution, the fibrinogen solution is not mixed with the thrombin solution at adjacent the rearward ejection port of the thrombin solution and therefore no coagulation occurs. On the other hand, there is a possibility that a small amount of thrombin solution is mixed with the fibrinogen solution at adjacent the forward ejection port of the fibrinogen solution and, if so, there occurs coagulations actively to plug the forward ejection nozzle. If the ejection nozzle of the thrombin solution is placed forward of that of the fibrinogen solution, the fibrinogen solution is not mixed with the thrombin solution at adjacent the rearward ejection nozzle of the fibrinogen solution, so that no coagulation occurs. Also, although a small amount of fibrinogen solution is mixed with the thrombin solution at adjacent the forward ejection nozzle of the thrombin solution, no vigorous reaction occurs. In conclusion, it is determined that no plugging occurs if the ejection port of the thrombin solution is placed forward of that of the fibrinogen solution. 
       Experiment 2 
       [0069]    A test was conducted by using the spray head in which the ejection port of the thrombin solution was disposed forward of that of the fibrinogen solution to see if the sprayed fibrinogen and thrombin solutions were well mixed with each other. 
         [0070]    As shown in  FIG. 11 , a spray head  101  for this test was manufactured by combining two spray heads  100  for use with BOLHEAL spray head commercially available from The Chemo-Sero-Therapeutic Research Institute. In particular, the opposed major surfaces of the spray heads were flattened by fling and then bonded to each other so that the ejection ports were displaced 6-7 millimeters from each other with respect to the ejecting direction. 
         [0071]    The syringe accommodating the thrombin solution was connected to the adaptor of the forward spray head and the syringe accommodating the fibrinogen solution was connected to the adaptor of the rearward spray head. In order to prevent the mutual interference of the syringes, the syringes were connected to the diagonally positioned adaptors, so that the centers of the ejection nozzles were spaced 5 millimeters away from each other. 
         [0072]    Using the combined spray head to which the syringes were assemble, the solutions were sprayed against a surface positioned about 1-10 centimeters away from the spray head. The solutions were mixed with each other and the adhesive was applied on the surface. This result showed that the sprayed solutions was well mixed with each other to produce the adhesive effectively on the application site by using the arrangement in which the ejection port of the thrombin solution was placed forward of that of the thrombin solution. 
       Experiment 3 
       [0073]    A comparative test was conducted to see the generation of plugging at the ejection ports, by using the combined spray head in test  2  and the conventional spray head shown in  FIG. 10 . 
         [0074]    In the test, the syringes were assembled to the combined and conventional spray heads to spray the solutions every 5 minutes in order to evaluate the performance of the plugging prevention function thereof. The spray heads were mounted on the syringes as described in the experiment 2. The performance of the plugging prevention function were ranked into three levels: Level A in which the fibrinogen and thrombin solutions were well sprayed, Level B in which a slight plugging occurred but nevertheless the solutions were sprayed, and Level C in which the plugging occurred to prevent the spraying, as shown in Table 1. 
         [0000]    
       
         
               
               
               
               
               
             
               
               
               
               
               
             
           
               
                   
                 TABLE 1 
               
               
                   
                   
               
               
                   
                   
                 Lapsed 
                 CONVENTIONAL 
                 COMBINED 
               
               
                   
                 No. 
                 Time (min. 
                 HEAD 
                 HEAD 
               
               
                   
                   
               
             
             
               
                   
               
             
          
           
               
                   
                 1 
                 0 
                 A 
                 A 
               
               
                   
                 2 
                 5 
                 A 
                 A 
               
               
                   
                 3 
                 10 
                 B 
                 A 
               
               
                   
                 4 
                 15 
                 C 
                 A 
               
               
                   
                 5 
                 20 
                 B 
                 A 
               
               
                   
                 6 
                 25 
                 — 
                 A 
               
               
                   
                   
               
             
          
         
       
     
         [0075]    As shown Table 1, in terms of the conventional spray head, the plugging caused at the ejection port for the fibrinogen solution in the fourth spraying (No. 4; Lapsed time was 5 min.), but the solution was sprayed by applying a greater force on the plunger in the fifth spraying. However, all the thrombin solution was completely consumed in the fifth spraying, so that no further spraying (i.e., sixth spraying) could be conducted. In contrast, no plugging occurred and the solutions were well sprayed in the sixth spraying. Also, for the combined head, no fibrinogen solution was observed at adjacent the ejection nozzle of the thrombin solution. 
         [0076]    From the experiment 3, it was verified that the arrangement in which the ejection nozzle of the thrombin solution being disposed forward of that of the fibrinogen solution prevents the generation of the plugging at the ejection port and ensures the intermittent applications of the adhesive. 
       Experiment 4 
       [0077]    An experiment was conducted to evaluate the plugging prevention performance in another condition different from that of experiment 3, for the combined spray head. 
         [0078]    Specifically, in the experiment 4, as shown in  FIG. 12 , employed were syringes with reduced diameters. The syringes were connected to upper and lower adjacent adaptors, respectively, in which the distance between the centers of the ejection ports was 4 millimeters. The spraying was performed every 30 minutes and the spraying performance was evaluated as in the experiment 3. 
         [0079]    The result is indicated in Table 2. 
         [0000]    
       
         
               
               
               
             
               
               
               
             
           
               
                 TABLE 2 
               
               
                   
               
               
                   
                 Lapsed 
                 COMBINED 
               
               
                 No. 
                 Time (min. 
                 HEAD 
               
               
                   
               
             
             
               
                   
               
             
          
           
               
                 1 
                 0 
                 A 
               
               
                 2 
                 30 
                 A 
               
               
                 3 
                 60 
                 A 
               
               
                   
               
             
          
         
       
     
         [0080]    As shown in table 2, no plugging occurred in each spraying and the solutions were well sprayed. Also, it was verified from the result of experiment 4 that no plugging occurred even when the distance between the centers of the ejection ports was reduced to 4 millimeters and the ejection intervals were increased to 30 minutes. 
       Experiment 5 
       [0081]    Another experiment was conducted to evaluate and compare the bonding performances for the combined and conventional spray heads. 
         [0082]    The syringes were connected to the combined spray head as in experiment 2. The biological tissue adhesive was applied to artificial blood vessels made of PTFE with a number of small apertures formed by penetrating 5-0 needle. The vessels were closed at the portions having the apertures by applying the biological tissue adhesive. The bonding performance was evaluated by measuring the withstanding pressure of the vessels using a pressure gage commercially available from NIDEC COPAL Corporation under the trade name PG-208-102VH-S. 
         [0083]    The result showed that the withstanding pressure obtained by using the conventional spray head was 202.5±75 mmHg and that obtained by using the combined spray head was 247.25±75.25 mmHg. This showed that the substantially the same withstanding pressure was obtained in the conventional and the combined spray head. 
         [0084]    Also, it was verified from the experiment 5 that substantially the same bonding performance was obtained when the ejection port of the thrombin solution be disposed forward of that of that of the fibrinogen solution.