WO2006011751A1

WO2006011751A1 - Pharmaceutical mixing assembly

Info

Publication number: WO2006011751A1
Application number: PCT/KR2005/002436
Authority: WO
Inventors: Young-Duck Kwon
Original assignee: Lg Life Sciences, Ltd.
Priority date: 2004-07-30
Filing date: 2005-07-27
Publication date: 2006-02-02
Also published as: KR20060011645A

Abstract

The pharmaceutical mixing assembly allows pharmaceuticals unstable in a mixed state with other components to be mixed with other pharmaceuticals or solvents immediately prior to injection or to continuous administration of the pharmaceuticals for a predetermined period. The pharmaceutical mixing assembly 100 comprises a pharmaceutical mixing member 200, a needle 300, a spring 400, a plunger 500, and a vial holding member 600 connected to the plunger 500. The assembly has a simple structure and a small number of components, thereby reducing manu¬ facturing costs and simplifying requirements for usage. The assembly allows pharmaceuticals to be mixed through a rear side of a vial when mixing the pharmaceuticals, thereby preventing damage of a stopper 850 in a pouring port 840 through which the needle passes, and ensuring that the pharmaceuticals for continuous administration can be stably mixed, and the mixed phar¬ maceuticals can be administered to a patient under sterile conditions.

Description

PHARMACEUTICAL MIXING ASSEMBLY

Technical Field

[1] The present invention relates to a pharmaceutical mixing assembly, and more par¬ ticularly to a pharmaceutical mixing assembly, designed to allow pharmaceuticals unstable in a mixed state with other components to be mixed with other pharma¬ ceuticals or solvents immediately prior to injection or to continuous administration of the pharmaceuticals for a predetermined period.

Background Art

[2] Pharmaceuticals are generally used as a composition comprising excipients and the like, in which the composition has a solid state, a suspension state or an emulsion state according to characteristics of the pharmaceuticals. One or more pharmaceuticals are often used as a mixture. As such, the pharmaceuticals can be used as a mixture with other compounds, such as, other kinds of pharmaceuticals, solvents, suspensions, emulsions, excipients, and the like.

[3] Meanwhile, for some pharmaceuticals, when the pharmaceuticals are maintained for a long time in such a mixed state, they become unstable, and thus it is necessary for some pharmaceuticals to be mixed immediately before they are used. For example, utrophin (Utrophin 16 IU; LG Life Sciences, Ltd.), one of the human growth hormones, is administered in a liquid state for injection. When an active protein is suspended in a solvent such as m-cresol for manufacturing the injectable utrophin, and maintained for a long time, there arises a problem of decomposition of the active protein. Accordingly, in the case of liquid for injection including the utrophin, it is necessary to mix the active protein and the solvent immediately prior to injection or continuous administration of the utrophin.

[4] Generally, since such a mixing operation must be stably performed under sterile conditions due to characteristics of the pharmaceuticals, it is not easy to perform the mixing operation. Thus, various devices have been developed to allow easy mixing of pharmaceuticals. For example, WO 97/25015 discloses a device for mixing an active component of one vial with a liquid component of another vial. However, since the device of the disclosure comprises a number of elements, it requires higher manu¬ facturing costs, and complicated usage instructions for users. In particular, when a minute amount of pharmaceuticals must be continuously administered to a patient for a predetermined period, structural problems also arise. In other words, in the device of the disclosure, it is necessary to employ a needle having a large inner diameter for enhancing mixing efficiency, whereas another syringe (or other particular devices) used for injecting a predetermined minute amount of mixed pharmaceuticals within a final vial into the patient employs another needle having a very small inner diameter. As a result, when a stopper (typically a rubber stopper) of the vial is perforated again by the slender needle of the other syringe after the stopper has been perforated by the large needle, the vial becomes difficult to maintain in a sterilized sealing state in spite of the resilience of the stopper, as the stopper is repetitiously perforated. Moreover, when the stopper remains in such a perforated state by the slender needle of the syringe for the continuous administration for a predetermined period, this problem is further exacerbated.

Disclosure of Invention Technical Problem

[5] Accordingly, it is needed in the art to provide a device, which has a simple structure and a small number of elements, thereby reducing manufacturing costs and simplifying requirements for usage, and, in particular, which can safely mix pharma¬ ceuticals required for continuous administration of a predetermined period while allowing administration of the mixed pharmaceuticals to a patient under sterile conditions.

[6] Accordingly, the present invention is directed to a pharmaceutical mixing assembly that substantially obviates one or more problems due to limitations and disadvantages of the related art. Technical Solution

[7] It is an object of the present invention to provide a pharmaceutical mixing assembly, which comprises a pharmaceutical mixing member, a needle, a spring, a plunger, and a vial holding member, and which allows pharmaceuticals to be mixed through a rear side of the vial by use of a short and thick needle when mixing the phar¬ maceuticals, thereby effectively preventing loss of the pharmaceuticals without causing damage of a stopper in a pouring port through which the needle passes for injection of the mixed pharmaceuticals.

[8] In accordance with one aspect of the present invention, the above and other objects can be accomplished by the provision of a pharmaceutical mixing assembly which comprises: a pharmaceutical mixing member including a bottle guide formed at a lower portion and having a lower end opened so as to allow a bottle to be inserted therethrough, a plunger engaging portion formed at an upper portion and having an upper end opened so as to allow a plunger to be engaged with the plunger engaging portion therethrough, and a closing member located between the bottle guide and the plunger engaging portion and respectively formed in a line at opposite sides of the closing member with a cannula extending towards the bottle guide and a needle fixing tube extending towards the plunger engaging portion, the plunger engaging portion having a first engaging groove formed at one side thereof so as to allow a first engaging protrusion of the plunger to be engaged with the first engaging groove and to move a predetermined distance up and down therein and a second engaging groove formed at the other side so as to allow a second engaging protrusion of the plunger to be engaged with the second engaging groove and to move a predetermined distance up and down therein; the plunger including a slender cylindrical body, an upper engaging portion formed at an upper portion of the body and having a thread formed thereon, and a lower cylindrical engaging portion formed at a lower portion of the body and having a diameter greater than that of the body, the lower engaging portion having the first engaging protrusion and the second engaging protrusion formed at opposite sides of the lower engaging portion such that the first and second engaging protrusions are engaged with the first and second engaging grooves, respectively, when the plunger is coupled to the pharmaceutical mixing member, and the body having an indentation depressed from the lower engaging portion so as to receive a spring; a needle having a lower end fixed to the needle fixing tube of the bottle guide and a sharp upper end located in a state of being inserted into the body of the plunger so that, when the needle is advanced, the needle penetrates the upper engaging portion of the plunger and is protruded from the upper engaging portion; the spring mounted between the needle fixing tube of the pharmaceutical mixing member and the indentation of the plunger to supply resilient restoring force to the needle; and a vial holding member provided as a separate member coupled to the pharmaceutical mixing member only in use, the vial holding member at least partially opened at a side surface so as to receive the vial having a cylindrical shape in a lateral direction, and opened at one end thereof so as to allow the body of the plunger to be inserted thereinto while being closed at the other end.

[9] Similar to a typical injection bottle, the bottle mountable to the pharmaceutical mixing assembly of the invention, more particularly, to the bottle guide, is also sealed at a lower end thereof, and has an upper pouring port sealed by a stopper formed of an elastic material, for example rubber, in a state of being filled with a content. The rubber stopper and the pouring port are integrated by a sealing cap such as metal cap. When the bottle is inserted to the bottle guide, the pouring port is directed towards an opened end of the bottle guide.

[10] The vial mountable to the pharmaceutical mixing assembly of the invention, more particularly, to the vial holding member, has a lower end sealed in a state of the vial being filled with the pharmaceuticals by the piston which is made of an elastic material (such as rubber) and can move along an inner cylindrical surface of the vial when force is applied to the piston, and has an upper pouring port sealed by a stopper made of the elastic material (such as rubber), in which the rubber stopper and the pouring port are integrated by a sealing cap such as metal cap. Such a structure of the vial can be easily found in a vial mounted in, for example, Autopen (Trademark) available from Owen Mumford GmbH, in G.B. When mounting the vial to the vial holding member, the vial is inserted to the vial holding member such that the lower end (piston) of the vial is located towards the open end of the vial holding member.

[11] The pharmaceuticals and associated materials to be mixed are contained in any of the bottle and vial, respectively, and are finally transferred to the vial. The associated materials may include other pharmaceuticals, solvents, and liquids (including suspensions, emulsions, and the like), which will be used for producing a desired phar¬ maceutical mixture. Preferably, before mixing, the material contained in the bottle (hereinafter referred to as "first material") is a solid material, and the material contained in the vial (hereinafter referred to as "second material") is a liquid material. Preferably, the first material is utrophin, and the second material is m-cresol.

[12] Preferably, an inner surface of the bottle guide has a fine annular protrusion formed at a portion corresponding to a neck of the bottle so as to allow the neck of the bottle to be stably coupled to the bottle guide when the bottle is inserted to the bottle guide.

[13] Preferably, the plunger further includes a relatively large sized assistant engaging protrusion formed above the second engaging protrusion of the plunger such that, when the assistant engaging protrusion is inserted into the second engaging groove of the plunger engaging portion, it is protruded through the plunger engaging portion, and the plunger engaging portion further includes an assistant engaging groove formed below the second engaging groove of the plunger engaging portion. With such a structure, during the operation of the assembly of the invention for mixing the pharma¬ ceuticals, the second engaging protrusion is further inserted from the second engaging groove, and is then engaged with the assistant engaging groove when a user wishes to stably maintain the needle in a state of penetrating the piston of the vial. On the other hand, when disengaging the second engaging protrusion, the second engaging protrusion is easily disengaged from the assistant engaging groove by pushing the assistant engaging protrusion with their fingernail.

[14] Preferably, the second engaging groove further has a groove extension formed at a lower end thereof in opposite directions.

[15] Preferably, the opened end of the vial holding member is formed with a hole whose diameter is greater than an outer diameter of the body of the plunger while being less than an outer diameter of a piston of the vial. Preferably, the closed end of the vial holding member is formed with a handle extending from opposite sides thereof so as to allow the vial holding member to be conveniently gripped. Preferably, a body of the vial holding member is partially formed with a sinuous portion so as to allow the vial holding member to be firmly gripped by hand. Brief Description of the Drawings

[16] The above and other objects, features and other advantages of the present invention will be more clearly understood from the following detailed description taken in conjunction with the accompanying drawings, in which:

[17] FIG. 1 is an exploded perspective view of a pharmaceutical mixing assembly in accordance with one embodiment of the present invention, illustrating components of the pharmaceutical mixing assembly;

[18] FIG. 2 is a cross-sectional view of the pharmaceutical mixing assembly, in which the components of FIG. 1 are combined with a bottle and a vial;

[19] FIG. 3 is a vertical cross-sectional view, a partial side sectional view, and a bottom view of a pharmaceutical mixing member of FIG. 1 ;

[20] FIG. 4 is a vertical cross-sectional view, partial left and right side sectional views, and a bottom view of a plunger of FIG. 1 ;

[21] FIG. 5 is a side sectional view, and a vertical cross-sectional of a vial holding member of FIG. 1 ;

[22] FIG. 6 is a step diagram for separating the vial from the vial holding member of

FIG. 5;

[23] FIG. 7 is a schematic view of the vial;

[24] FIG. 8 is a step diagram for assembling some components of the pharmaceutical mixing assembly shown in FIG. 1 ;

[25] FIGS. 9 to 15 are step diagrams illustrating a mixing process for pharmaceuticals using the pharmaceutical mixing assembly shown in FIG. 1; and

[26] FIG. 16 is a partial cross-sectional view illustrating an engaging manner of a plunger engaging portion and a lower engaging portion of the pharmaceutical mixing member of the pharmaceutical mixing assembly shown in FIG. 1. Best Mode for Carrying Out the Invention

[27] Preferred embodiments of the invention will now be described with reference to the drawings. It should be noted that the embodiments are disclosed for the purpose of il¬ lustration, and do no limit the scope of the invention.

[28] In FIG. 1, components of a pharmaceutical mixing assembly in accordance with one embodiment of the invention are shown in an exploded state. For convenience of understanding, some components are shown in a cross-sectional view or a partial cross-sectional view. The pharmaceutical mixing assembly 100 comprises a phar¬ maceutical mixing member 200, a needle 300, a spring 400, a plunger 500, and a vial holding member 600 connected to the plunger 500, which are sequentially assembled along solid line arrows. The vial holding member 600 may be connected to the plunger 500 only in use. In use, a bottle 700 is inserted into the pharmaceutical mixing member 200, and a vial 800 is mounted to the vial holding member 600. In FIG. 2, the phar¬ maceutical mixing assembly 100 having the bottle 700 and the vial 800 assembled thereto is shown. The respective components will be described in detail as follows.

[29] In FIG. 3, a vertical cross-sectional view, a partial side sectional view, and a bottom view of the pharmaceutical mixing member 200 of FIG. 1 are shown for convenience of understanding. The pharmaceutical mixing member 200 has a sub¬ stantially cylindrical shape in which a lower portion thereof has a relatively large diameter, and comprises a closing member 230 which has a cannula 210 and a needle fixing tube 220 respectively formed in a line at the center of opposite sides of the closing member. The cannula 210 and the needle fixing tube 220 communicate via a penetrating path 240. A bottle guide 250 is located below the closing member 230, and is opened at a lower end. The inner surface of the bottle guide 250 substantially corresponds to an outer shape of the bottle (not shown in FIG. 3). The inner surface of the bottle guide 250 is formed with a fine annular protrusion 252 at a portion cor¬ responding to a neck of the bottle 700 (see FIG. 1) so as to allow the bottle 700 to be stably coupled to the bottle guide 250 when the bottle 700 is inserted thereto. The phar¬ maceutical mixing member 200 includes a plunger engaging portion 260, which has a first engaging groove 262 formed at one side thereof so as to allow a first engaging protrusion 540 of a plunger 500 as shown in FIG. 4 to move up and down in an engaged state, and a second engaging groove 264 formed at the other side so as to allow a second engaging protrusion 550 of the plunger 500 to move up and down in the engaged state. As with the first engaging groove 262, the second engaging groove 264 is vertically elongated. An assistant engaging groove 268 is formed below the second engaging groove 262. As described below, when the second engaging protrusion 550 having been located at the second engaging groove 264 is further pushed at a certain operating stage of the pharmaceutical mixing assembly 100, the assistant engaging groove 268 provides an engaging groove where the second engaging protrusion 550 can be engaged for stably maintaining the needle in a state of penetrating a piston of the vial. Additionally, the second engaging groove 264 has a groove extension 266 formed at a lower end thereof in opposite directions, thereby making it convenient to compress an assistant engaging protrusion 552 (see FIG. 4) with fingernail in order to push the second engaging protrusion 264 at the certain operating stage of the pharmaceutical mixing assembly 100, as described below.

[30] In FIG. 4, a vertical cross-sectional view, partial left and right side sectional views, and a bottom view of the plunger 500 are shown. Referring to FIG. 4, the plunger 500 comprises a slender cylindrical body 510, an upper engaging portion 520 having a thread formed thereon, and a cylindrical lower engaging portion 530. As shown in FIG. 2, the upper engaging portion 520 is coupled to a piston of the vial 800, which is formed with an indentation having a female screw corresponding to the thread of the upper engaging portion 520. The body 510 is formed with an indentation 512 for receiving the spring 300 (see FIG. 1). As shown in FIG. 2, since the lower engaging portion 530 is inserted into the plunger engaging portion 260 of the pharmaceutical mixing member 200, it has an outer diameter corresponding to an inner diameter of the plunger engaging portion 260. The lower engaging portion 530 is formed at one side with the first engaging protrusion 540, and at the other side with the second engaging protrusion 550. The first and second engaging protrusions 540 and 550 have opposite sides spaced from the lower engaging portion 530 so as to resiliently engage with the lower engaging portion 530, respectively. Additionally, the lower engaging portion 530 has a relatively large sized assistant engaging protrusion 552 formed above the second engaging protrusion 550, such that the assistant engaging protrusion 552 is engaged with the second engaging groove 264, and protruded through the plunger engaging portion 260.

[31] In FIG. 5, a side sectional view, and a vertical cross-sectional view of the vial holding member 600 are shown, and in FIG. 6, a step diagram illustrating separation of the vial 800 from the vial holding member is shown. Referring to FIGS. 5 and 6, the vial holding member 600 is entirely opened at one side surface 610 so as to receive the vial 800 in a lateral direction, and is partially opened at the other side surface 620 so as to allow easy separation of the mounted vial 800 therefrom. As a result, upper and lower portions of the other side surface 620 are formed with openings 622 and 624, re¬ spectively. Additionally, the vial holding member 600 is formed at one end thereof with a hole 530 greater than an outer diameter of the body 510 and less than an outer diameter of the piston 820 of the vial 800 so as to allow the body 510 (see FIG. 4) of the plunger 500 (see FIG. 4) to move in an inserted state in use. As a result, when the plunger 500 is pulled from the vial holding member 600 with the upper engaging portion 520 (see FIG. 4) of the plunger 500 coupled to the piston 820 of the vial 800, the piston 820 is not separated from the vial. Additionally, the other end of the vial holding member 600 is closed, and has a handle 640 extending at opposite sides thereof so as to allow the vial holding member 600 to be conveniently gripped. The vial 800 is mounted to the vial holding member 600 through the open side surface 610, and is separated therefrom by compressing the vial 800 through the opening 624 and/or compressing a side corresponding to the opening 622 as shown in FIG. 6. Moreover, a body of the vial holding member 600 has a sinuous portion 650 formed at a portion thereof so as to allow the body to be firmly gripped by a user.

[32] In FIG. 7, a schematic view of the vial 800 is shown. Referring to FIG. 7, the vial

800 is filled with a material 900, and is sealed at the lower end thereof by the piston 820 made of an elastic material (for example, rubber). The piston 820 can move inside a cylindrical body 830 of the vial 800 when force is applied to the piston 820. An upper pouring port 840 is sealed by a stopper 850 made of an elastic material such as rubber. The upper pouring port 840 and the stopper 850 are integrated by a metal cap 860, thereby constituting a head 810. The material 900 is preferably a liquid at standard temperature and pressure, for example, m-cresol, which can disperse utrophin. As described below with reference to FIGS. 9 to 15, the material 900 is drawn from the vial 800 through the needle 300 (see FIG. 2) penetrating the piston 820 in order to perform pharmaceutical mixing, and pharmaceuticals mixed in the bottle 700 are introduced into the vial 800. As a result, since the vial 800 can be used in a state of being mounted to a particular injection device, such as an Autopen (trademark) without damaging the stopper 850 of the pouring port 840, the problem of the prior art does not occur.

[33] In FIG. 8, a step diagram for assembling some components of the pharmaceutical mixing assembly 100 of FIG. 1 is shown. Referring to FIG. 8, after the needle 300, the spring 400 and the plunger 500 are assembled to the pharmaceutical mixing member 200, the pharmaceutical mixing member 200 is coupled to the vial 800 (see FIG. 7) equipped to the vial holding member. Referring to FIGS. 7 and 8, when the plunger 500 is coupled to the vial 800, the thread of the upper engaging portion 520 is engaged with the indentation 822 of the piston 820, more specifically, with the female screw of the indentation 822 by rotating the plunger 500. In FIG. 2, a vertical cross-sectional view of the pharmaceutical mixing assembly 100 having the components assembled by the above process is shown.

[34] FIGS. 9 to 15 are step diagrams illustrating a mixing process for pharmaceuticals contained in the vial 800 and the bottle 700. For convenience of description, a first material contained in the bottle 700 will be referred to as utrophin, and a second material contained in the vial 800 will be referred to as m-cresol.

[35] Referring to FIG. 9, the bottle 700 is inserted into the bottle guide 250 of the phar¬ maceutical mixing member 200 in the pharmaceutical mixing assembly 100, in which the overall components comprising the vial holding member 600 with the vial 800 mounted therein are completely assembled. During insertion of the bottle 700, since the cannula 210 penetrates a stopper 710 of the bottle 700, the penetrating path 240 connected to the needle 300 is communicated with the bottle 700.

[36] Referring to FIG. 10, when pushing the bottle 700 with the plunger 500 gripped and fixed by hand into the vial guide 250, an upper end 310 of the needle 300 penetrates and is inserted into the piston 820 of the vial 800 coupled to the upper engaging portion 520 of the plunger, and the spring 400 positioned between the needle 300 and the inner surface of the plunger 500 is compressed. Operational relationship between the lower engaging portion 530 of the plunger 500 and the plunger engaging portion 260 of the pharmaceutical mixing member 200 in this process will be described in detail with reference to FIG. 16. Referring to FIG. 16, when force is not applied to the plunger, the first and second engaging protrusions 540 and 550 respectively located at upper portions of the first and second engaging grooves 262 and 264 are lowered by restoring force of the spring 400, and then the second engaging protrusion 550 is engaged with the assistant engaging groove 268 formed below the second engaging groove 264. The plunger 500 stops lowering when the first engaging protrusion 540 reaches the annular protrusion 252 formed above the closing member 230.

[37] Referring to FIG. 11, when pulling down the vial holding member 600 with the upper end of the needle 300 penetrating the piston 820 of the vial 800, the piston 820 is raised along the inner surface of the vial 800, so that the m-cresol contained in the vial 800 is compressed, introduced into the bottle 700 along the penetrating path of the needle 300, and mixed with the utrophin contained in the bottle 700. After finishing this process, an utrophin dispersed liquid is produced by uniformly mixing the utrophin and the m-cresol contained in the bottle 700 in such a manner of reversing and shaking the pharmaceutical mixing assembly.

[38] Referring to FIG. 12, when pulling the handle 640 of the vial holding member 600 with the overall pharmaceutical mixing assembly 100 reversed, the utrophin dispersed liquid mixed in the bottle 700 is introduced back into the vial 800 through the penetrating path of the needle 300.

[39] Referring to FIG. 13, when releasing the engagement between the lower engaging portion 530 of the plunger 500 and the plunger engaging portion 260, the upper end of the needle 300 having penetrated the piston 820 is separated from the piston 820. The process of releasing the engagement can be appreciated more specifically with reference to FIG. 16. That is, when pressing the assistant engaging protrusion 552 of the lower engaging portion 530 protruded from the second engaging groove 264, the lower engaging portion 530 is changed in shape as indicated by a dotted line. Then, the second engaging protrusion 550 is separated from the assistant engaging groove 268, and the lower engaging portion 530 is raised by the restoring force of the spring 400. Rise of the lower engaging portion 530 is stopped when the first engaging protrusion 540 and the assistant engaging protrusion 552 reach the upper ends of the first and second engaging grooves 262 and 264. Accordingly, as shown in FIG. 13, even though the engagement between the lower engaging portion 530 and the plunger engaging portion 260 is released, the plunger 500 is prevented from being completely separated from the pharmaceutical mixing member 200.

[40] Referring to FIGS. 14 and 15, the vial holding member 600 having the vial 800 mounted therein is separated from the pharmaceutical mixing assembly 100 by rotating the plunger 500 in a reverse direction to the case of engaging the vial holding member 600 to the assembly 100. At this time, in order to prevent the piston 820 from idling along the inner surface of the vial 800, it is desirable that the plunger 500 be rotated while the vial 800 exposed through the first and second openings 622 and 624 of the vial holding member 600 is gripped by hand. A process for separating the vial 800 containing the utrophin dispersed liquid can be performed as described above with reference to FIG. 4b. Industrial Applicability

[41] As apparent from the above description, the pharmaceutical mixing assembly of the invention has a simple structure and a small number of components, thereby reducing manufacturing costs and simplifying requirements for usage, and is designed to allow pharmaceuticals to be mixed through a rear side of a vial when mixing the pharma¬ ceuticals, which prevents damage of a stopper in a pouring port through which a needle passes for injection of the mixed pharmaceuticals, thereby ensuring that the pharma¬ ceuticals required, in particular, for continuous administration of a predetermined period can be stably mixed, and the mixed pharmaceuticals can be administered to a patient under sterile conditions.

[42] Although the preferred embodiments of the present invention have been disclosed for illustrative purposes, those skilled in the art will appreciate that various modi¬ fications, additions and substitutions are possible, without departing from the scope and spirit of the invention as disclosed in the accompanying claims.

Claims

[1] A pharmaceutical mixing assembly for mixing a first material contained in a bottle and a second material contained in a vial, comprising: a pharmaceutical mixing member including a bottle guide formed at a lower portion and having a lower end opened so as to allow the bottle to be inserted therethrough, a plunger engaging portion formed at an upper portion and having an upper end opened so as to allow a plunger to be engaged with the plunger engaging portion therethrough, and a closing member located between the bottle guide and the plunger engaging portion and respectively formed in a line at opposite sides of the closing member with a cannula extending towards the bottle guide and a needle fixing tube extending towards the plunger engaging portion, the plunger engaging portion having a first engaging groove formed at one side thereof so as to allow a first engaging protrusion of the plunger to be engaged with the first engaging groove and to move a predetermined distance up and down therein and a second engaging groove formed at the other side so as to allow a second engaging protrusion of the plunger to be engaged with the second engaging groove and to move a predetermined distance up and down therein; the plunger including a slender cylindrical body, an upper engaging portion formed at an upper portion of the body and having a thread formed thereon, and a lower cylindrical engaging portion formed at a lower portion of the body and having a diameter greater than that of the body, the lower engaging portion having the first engaging protrusion and the second engaging protrusion formed at opposite sides of the lower engaging portion such that the first and second engaging protrusions are engaged with the first and second engaging grooves of the pharmaceutical mixing member, respectively, when the plunger is coupled to the pharmaceutical mixing member, and the body having an indentation depressed from the lower engaging portion so as to receive a spring; a needle having a lower end fixed to the needle fixing tube of the bottle guide and a sharp upper end located in a state of being inserted into the body of the plunger so that, when the needle is advanced, the needle penetrates the upper engaging portion of the plunger and is protruded from the upper engaging portion; the spring mounted between the needle fixing tube of the pharmaceutical mixing member and the indentation of the plunger to supply resilient restoring force to the needle; and a vial holding member provided as a separate member coupled to the phar¬ maceutical mixing member only in use, the vial holding member at least partially opened at a side surface thereof so as to receive the vial having a cylindrical shape in a lateral direction, and opened at one end so as to allow the body of the plunger to be inserted thereto while being closed at the other end.

[2] The assembly according to claim 1, wherein the first material is a solid material, and the second material is a liquid material.

[3] The assembly according to claim 2, wherein the first material is utrophin, and the second material is m-cresol.

[4] The assembly according to claim 1, wherein an inner surface of the bottle guide has a fine annular protrusion formed at a portion corresponding to a neck of the bottle so as to allow the neck of the bottle to be stably coupled to the bottle guide when the bottle is inserted into the bottle guide.

[5] The assembly according to claim 1, wherein the plunger further includes a relatively large sized assistant engaging protrusion formed above the second engaging protrusion of the plunger such that, when the assistant engaging protrusion is inserted into the second engaging groove of the plunger engaging portion, it is protruded through the plunger engaging portion, and the plunger engaging portion further includes an assistant engaging groove formed below the second engaging groove of the plunger engaging portion.

[6] The assembly according to claim 1, wherein the second engaging groove further has a groove extension formed at a lower end thereof in opposite directions.

[7] The assembly according to claim 1, wherein the opened end of the vial holding member is formed with a hole whose diameter is greater than an outer diameter of the body of the plunger while being less than an outer diameter of a piston of the vial.

[8] The assembly according to claim 1, wherein the closed end of the vial holding member is formed with a handle extending from opposite sides thereof so as to allow the vial holding member to be conveniently gripped.

[9] The assembly according to claim 1, wherein a body of the vial holding member is partially formed with a sinuous portion so as to allow the vial holding member to be firmly gripped by hand.