WO2006076492A2

WO2006076492A2 - Reconstitution and transfer device and method

Info

Publication number: WO2006076492A2
Application number: PCT/US2006/001080
Authority: WO
Inventors: Helen Shi Liu; John Pipinias; Steven Tortorella
Original assignee: Whatman, Inc.
Priority date: 2005-01-13
Filing date: 2006-01-12
Publication date: 2006-07-20
Also published as: WO2006076492A3

Abstract

An apparatus and a method for transferring a first substance from a first receptacle into a second receptacle containing a second substance under reduced pressure, mixing the substances and delivering the mixture aseptically to a receiver. The apparatus includes a main body having a first and second ends, a first receptacle receiver at the first end and a second receptacle receiver at the second end. A first passageway connects the first and second ends and a second passageway connects the second end to a side opening. A closure member removeably engages the side opening. A piercing cannula having multiple lumens extends from the second end for connecting the interior of the second receptacle with the first and second passageways, and another piercing cannula having a lumen is removeably connected to and extends from the first end to connect the interior of the first receptacle with the first passageway.

Description

RECONSTITUTION AND TRANSFER DEVICE AND METHOD

This application claims priority from United States Provisional Application No. 60/643,548 entitled "Novel Reconstitution and Transfer Device" filed 13 January 2005, the entire content of which is incorporated herein by reference.

BACKGROUND OF THE INVENTION

1. FIELD OF INVENTION

The present invention relates generally to transfer devices and methods for mixing substances. More particularly, the apparatus and method of the present invention concern transferring a first substance into a container containing a second substance, mixing the first substance and second substance and delivering the resulting mixture aseptically to a delivery device.

2. STATE OF THE ART

Reconstitution is often necessary prior to the administration of a therapeutic agent to a patient. Specifically, reconstitution typically consists of injecting an appropriate diluents into a container previously filled with a predetermined quantity of a therapeutic agent and mixing the therapeutic agent with the diluents substance. The resulting mixture then is transferred into a syringe or other transfer device for administration to the patient orally, by injection or otherwise.

In the past, the reconstitution process often was achieved by sequentially filling a conventional syringe with a diluents composition, piercing the seal of container of medicine with a needle attached to the syringe, injecting the diluents into the container of medicine, intermixing the diluents with the medicine in the container, and aspirating resulting mixture back into the same syringe or into a different syringe. This reconstitution process has several drawbacks. Among these drawbacks are difficulties in operation, contaminations of the therapeutic mixture, and inaccuracies in the administration of the resultant mixtures. Specifically in this regard, reconstitution typically required an operator to possess a certain degree of skill, dexterity and focus. A lack of any of these characteristics often was found to result needle stick injuries. In the United States needle sticks are the cause of nearly 600,000 injuries annually. In addition, needle stick injuries can result in the need for costly treatments. This is particularly the case because such injuries often subject the injured individual to high risks of disease transmission arising from blood-borne pathogens and other forms of contamination. In response to these issues, in November 2000, the United States enacted the Needle Safety and Prevention Act (NSPA) in an attempt to reduce this type of disease transmission and/or injury. In addition, the Occupational Safety and Health Administration (OSHA) of the United States Department of Labor have revised its standards and mandates for the implementation of safe needle using devices.

Contamination in the administration of reconstituted medicines may result in serious complications to patients. Specifically, such contamination has been found to result from breaches of sterile conditions or particulates that are not completely dissolved during the reconstitution process among other sources. This problem has been found to be particularly acute in the self-administration of medicines in a home-care environment.

Furthermore, because reconstituted medicine in a container typically is transferred into a syringe through a needle, inconsistencies in the depth of the needle insertion into the reconstituted material in the container may result in incomplete transfer of the mixture or the transfer of a mixture in the wrong concentration, both of which have been found to cause sub- optimal administration of the medicinal mixtures involveji. Exemplary known reconstitution and/or transfer devices include those shown in U.S. Pat. Nos: 6,610,040, 6,558,365 (including its corresponding EP 1,329,210), 6,379,340, 6,238,372, 6,113,583, 6,071,270, 6,063,068, 6,022,339, 5,989,237, 5,743,312, 5,566,729, 5,358,236 (including its corresponding WO 0,007,539) 5,304,163, 5,074,844, 5,074,844, 5,049,129, 4,898,209 (including its corresponding CA 1,327,776), 4,874,366, 4,759,756, 4,607,671, World Intellectual Property Organization International Publication Nos: 03/082398, 02/062288, 02/00290, 01/68166, 99/27886, 86/03417; European Publication Nos: 1 219 283 A2, 0 521 460 Al; and U.S. Pat. App. Nos: 2003 0,199,846.

Most significantly among these patents, U.S. Pat. 6,558,365 describes a fluid transfer device that includes a plastic spike for piercing elastomeric seals found on typical medicine containers, and an adapter that is used to shield the plastic spike and to receive the container. Two of these devices apparently may be connected to one another so as to form a liquid flow pathway through the respective spikes that may be used in the course of drug reconstitution. In this case, after the drug has been reconstituted, the connected devices are disconnected, and a needleless syringe is connected with one of the devices to transfer the resultant mixture. However, this disclosure does not provide any particular capturing mechanisms to prevent solid particles from entering into the syringe or other forms of contamination.

U.S. Pat. 6,238,372 describes another fluid transfer device. In particular, that device includes a housing that contains three ports, one for receiving a syringe, one for establishing a liquid flow path into a medicine container, and one for fluid transfer. In this device, two of the ports are connected for reconstitution. However, this device has been found to be too bulky and awkward to be handled conveniently during reconstitution. Also, a third port is needed for fluid transfer thereby complicating the reconstitution process.

U.S. Pat. 5,743,312 describes yet another drug reconstitution device, but fails to include any fluid transfer mechanism. Accordingly, a conventional syringe is required to transfer the mixture according to the latter disclosure. In addition, European Patent No. 0 521 460 Al describes a fluid transfer device that can be used for both reconstitution and transfer purposes. That device is designed to include a filtration mechanism for the purpose of keeping the drug environment sterile and preventing undesired large particles from entering into the syringe or other transfer device. Therefore, the main drawbacks of this design are that it also is bulky and awkward, and that it is so complex that its manufacture is a challenging task.

Accordingly, the objects and advantages of the present invention that is contemplated to address the foregoing deficiencies in the art include the following:

1. simplicity of the reconstitution and transfer operation,

2. avoidance of the chance of inadvertent needle stick injuries,

3. the maintenance of a sterile environment and the prevention of

contamination, and

4. the assured provision of proper dosages of medicine.

Further objects and advantages of the present invention will become apparent to those skilled in the art from a consideration of the following discussion of several alternative preferred embodiments of the invention in view of the appended drawings.

SUMMARY OF INVENTION

In a preferred embodiment of the present invention, a reconstitution and transfer device includes a main body, and first and second receptacle receivers connected with the main body such that the interiors of receptacles engaging the respective receptacle receivers are connected to one another through a passageway through the main body. More specifically, lumens of first and second piercing cannulas are connected respectively with a first passageway through the main body such that the piercing cannulas are capable of piercing typical seals covering the open ends of receptacles received by the respective receptacle receivers and transferring a substance from one of the receptacles to the other therethrough. Further, a side opening associated with a sidewall of the main body between its ends is provided which is adapted to have a closure member removeably disposed therein. This side opening, when the closure member is disassociated from the main body, is capable of releasing a reduced pressure in a receptacle which is adapted to receive a substance from the other receptacle through the second passageway through the main body to the surrounding atmosphere in order to facilitate the aspiration of the mixed substances contained therein into a transfer device.

More particularly, the present invention provides an apparatus for mixing a first substance contained within a first receptacle (typically a liquid) with a second substance (typically a powder) contained within a second receptacle under reduced pressure. The first and second receptacles each respectively include a sealed open end. Further, the apparatus of the present invention is adapted to facilitate a transfer of the resultant mixture to an aspirator.

More particularly, the apparatus of the present invention generally includes a main body portion having a longitudinal axis, a peripheral surface, and opposing first and second ends. In addition, the main body portion defines a first substantially longitudinal passageway connecting the first ^"end of the main body to its second^' end and a second passageway connecting the second end of the main body to an opening in its peripheral side surface. A first receptacle receiver is located at the first end of the main body and a second receptacle receiver is located at the second end of said main body, the first and second receptacle receivers being substantially centered on the longitudinal axis and adapted to respectively receive and releasably hold at least the sealed open ends of the first and second receptacles.

A first piercing cannula is removeably connected with the main body adjacent the first end of the main body so as to extend substantially along the longitudinal axis of the main body into the first receptacle receiver. The first cannula defines a longitudinal lumen connecting an outer piercing end that is surrounded by the peripheral walls of the first receptacle receiver with the first passageway through the main body. A second piercing cannula extends substantially longitudinally from the second end of the main body into the second receptacle receiving portion. The second cannula defines a pair of substantially parallel longitudinal lumens that respectively connect an outer piercing end that is surrounded by the peripheral walls of the second receptacle receiver with the first passageway and the second passageway, respectively.

Also, a closure member is removably associated with the second passageway at its opening into the peripheral surface of said main body.

In preferred embodiments of the apparatus of the present invention, a sterile air filter extends across the second passageway substantially adjacent to a cavity in the peripheral wall of the main body adapted to removeably receive the closure member. In addition, a first particle- capturing filter extends across the lumen of the first cannula substantially adjacent to its connection with the first passageway. Further, a second particle-capturing filter extends across the first passageway substantially adjacent to its connection to the lumen of the first cannula. The peripheral walls of the first and second receptacle receivers are adapted to substantially elastically deflect outwardly so as to allow the secure, yet removable, receipt of a sealed open end of one of the receptacles in the cavity formed thereby. Accordingly, the peripheral walls may, for example, define a plurality of circumferentially spaced longitudinal slots and inwardly extending projections adjacent the outer edge of each of the portions of the peripheral wall between each pair of longitudinal slots for releaseably retaining a sealed open end of a receptacle in the cavity formed thereby.

In another configuration, the peripheral wall of the first receptacle receiver may be as just described (i.e., include circumferentially spaced, longitudinal slots) while the peripheral wall of the second receptacle receiver defines instead of the above-mentioned longitudinal slots having inwardly extending projections therebetween, an inwardly extending projection adjacent to its outer edge and a slot that extends longitudinally toward the main body from its outer edge to one end of a substantially circumferentially disposed slot that extends approximately one-halfway around the circumference of the second receptacle receiver. In this alternative construction, a second receptacle defining a projection receiving portion adjacent to its sealed open end (such as an edge of a cap) may be easily, yet securely, inserted into the second receptacle receiver by virtue of the resilient movability of the outer circumferential portion of the peripheral wall of the second receptacle receiver located between the circumferentially extending slot and the outer edge of the peripheral wall. Indeed, it has been found that this construction further facilitates the secure, yet removable, disposition of a second receptacle in the second receptacle receiver in the present invention in those cases in which it is important to load the second receptacle receiver quickly in order to avoid liquid loss from the first receptacle and to maintain the reduced pressure in the second receptacle for drawing the first substance into the second receptacle through the first passageway through the main body. Still further, either separately or in combination with the last mentioned alternative, it is contemplated that after the transfer of the first substance from the first receptacle into the second receptacle has be completed, the first receptacle and the cannula extending longitudinally into the first receptacle receiver are to be removable from the first receptacle receiver together. The removal of these elements together from the first receptacle receiver provides immediate open access to the first passageway through the main body and thence to the interior of the second receptacle for the aspiration of the mixed substances from the first end of the main body through the longitudinal passageway.

To that end, the first receptacle receiver defines a central, hollow, cylindrical portion surrounding a longitudinal projection of the first passageway into the first receptacle receiver having a threaded external surface. The first cannula is mounted on a fitting defining a central passageway connecting the lumen of the first cannula with the first passageway of the main body. That fitting includes a first portion adapted to screw onto the exterior of the hollow, cylindrical portion just described and a second portion adapted to project into the central hollow portion of the longitudinally cylindrical portion (i.e., a so-called Luer fitting).

In one possible configuration, the fitting just mentioned defines a plurality of radially extending projections substantially adjacent the location at which the cannula enters the fitting. Each of these projections is adapted to pierce the seal of a receptacle inserted into the first receptacle receiver adjacent to the location at which the first cannula pierces that seal.

The result of this construction is that axial rotation of the first receptacle mounted in the first receptacle receiver causes the projections adjacent to the joinder of the first cannula to its mounting fitting to bear circumferentially against the seal. In this way, the fitting may be unscrewed from the cylindrical portion by axial rotation of the first receptacle. Also, by virtue of the tight frictional engagement of the cannula and the radial projections with the seal, the first cannula, its associated fitting and the first receptacle can be easily removed from the first receptacle receiver together. As a result, the opening from the first receptacle receiver into the first passageway through the hollow longitudinal projection adjacent to the base of the first receptacle receiver is immediately available for the receipt of an aspirator (such as a syringe) for drawing the mixed substances out of the second receptacle mounted in the second receptacle receiver.

Alternatively, the fitting adapted to mount the first cannula onto the central cylindrical hollow portion may include a handle extending substantially radially outwardly from the fitting through a slot in the peripheral wall of the first receptacle receiver to an outer handle end. In this case, the longitudinal slots in the peripheral wall of the first receptacle receiver are replaced with a slot that extends in a spiral toward said main body from an inner end of a longitudinal slot that extends from the outer edge of the peripheral wall a preselected distance toward said main body. This construction permits movement of the handle from a closed end of the spiral slot when the fitting fully engages the hollow cylindrical projecting portion in the first receptacle receiver along the spiral slot in a manner that acts to unscrew the fitting from the cylindrical hollow portion. The pitch of the threads of the engaged fitting and those of the exterior of the hollow cylindrical portion are matched with the spiral of the slot in the peripheral wall of the first receptacle receiver such that when the handle reaches the inner end of the longitudinal slot, the fitting is fully released from its threaded engagement with the longitudinally extending cylindrical portion. Hence, the fitting, the first cannula and the first receptacle can be removed from the first receptacle receiving portion together with the assistance of the handle portion guided outwardly through the longitudinal slot portion of the slot formed in the peripheral wall of the first receptacle receiver.

The method for mixing a first substance contained within a first receptacle with a second • substance contained under reduced pressure within a second receptacle, the first and second receptacles each respectively having an opening sealed with a pierceable seal, and for facilitating a transfer of the resultant mixture to an aspirator or other delivery device now will be summarized.

Utilizing the apparatus discussed above, a sealed end of a first receptacle containing a first substance (typically a liquid) is inserted into the first receptacle receiver such that the first cannula pierces the sealed end of the first receptacle and the first receptacle is releasably held in the first receptacle receiving portion. This is usually accomplished with the first receptacle in an upright position (i.e., with its sealed open end facing upwardly). Thereafter, a sealed end of the second receptacle is inserted into the second receptacle receiver such that the second cannula pierces the sealed end of the second receptacle and the second receptacle is releasably held in the second receptacle receiver. If the substance in the first receptacle is a liquid, that substance will tend to leak out of the first passage through the main body as the second receptacle is mounted in the second receptacle receiver. Accordingly, a quick and sure mounting of the second receptacle is desired, even though the first passageway diameter is small thereby limiting the volume of the first substance that flows therethrough per unit time. It has been found that appropriate mounting of the second receptacle is possible with limited spillage, however, particularly when the slot in the peripheral wall of the second receptacle receiver extends circumferentially rather than solely longitudinally therein. Thereafter, the apparatus having the first and second receptacles mounted in the first and second receptacle receivers is inverted so as to place the first receptacle in an upside down position. As mentioned previously, the first substance is typically a liquid and the second substance is typically a powder, but the nature of the substances may vary from this so long as the first substance can flow through the first cannula into the longitudinal passageway in the main body and thence through the second cannula into the second receptacle.

In this way, the first substance contained in the first receptacle is transferred into the second receptacle through the first passageway and second cannula by gravity and under the applied drawing force of the reduce pressure in said second receptacle. In other words, the first receptacle is mounted in the first receptacle receiving portion and thereafter the second receptacle is mounted in the second receptacle receiving portion such that upon the piercing of the seal of the second receptacle the reduced pressure therein provided by the manufacturer of the medicinal or other material contained therein creates a drawing force that pulls the first substance from the first receptacle into the second receptacle with sufficient force to cause a mixing of the first and second substances within the second receptacle.

Obviously, if the resultant mixing is deemed to be insufficient, the second receptacle may be shaken while mounted in the apparatus to complete satisfactory mixing of the first and second substances.

Once the first substance has been adequately transferred to the second receptacle and mixed with the second substance contained therein, the closure member associated with the opening in the peripheral wall to the second passageway in the main body is removed or otherwise opened. In addition, the first cannula, its associated fitting and said first receptacle are removed together from the first receptacle receiver by unscrewing the fitting holding the first cannula from the hollow cylindrical projection at the base of the first receptacle receiver and pulling the cannula, the fitting and the first receptacle out of the first receptacle receiving portion thereby disengaging any locking engagement or other feature tending to retain the open end of the first receptacle within the first receptacle receiving portion) as generally discussed above.

After the first receptacle, the fitting and the first cannula have been removed together from the first receptacle receiving portion, the fitting portion of an aspirator such as a syringe is attached to the hollow cylindrical portion at the base of the first receptacle receiver and the mixed first and second substances in the second receptacle are drawn out of the second receptacle into the reservoir of the aspirator.

In the latter regard, since the drawing force applied by the aspirator typically is significant, the open second passageway assures the equalization of the pressure inside the second receptacle with the outside during aspiration of the mixed first and second substances. This acts to avoid the potential for the creation of an air pressure lock in the second receptacle/first passageway that could prevent satisfactory aspiration of the mixed substances.

BRIEF DESCRIPTION OF THE DRAWINGS

These and other features and advantages of the present invention will become clear to those skilled in the art by virtue of the following detailed description of the preferred embodiments thereof taken in conjunction with the attached drawings in which:

Fig. IA is an exploded side elevation of a first embodiment of an apparatus in accordance

with the invention;

Fig. IB is a cross sectional view taken along the line A-A of the first embodiment of the

apparatus of the invention shown in Fig. 1;

Fig. 2 A is a side elevation of the first embodiment of the apparatus in accordance with

the invention in assembled condition;

Fig. 2B is a cross sectional view taken along the line A-A of the first embodiment of the

apparatus in accordance with the invention shown in Fig. 2A;

Fig. 3 A is a side elevation of the first embodiment of the apparatus in accordance with

the invention of Fig. 2 showing a first receptacle engaging the first receptacle

receiver;

Fig. 3B is a cross-sectional view taken along the line A-A of Fig. 3 A;

Fig. 4 A is a side elevation of the first embodiment of the apparatus in accordance with

receiver and a second receptacle engaging the second receptacle

receiver; Fig. 4B is a cross sectional view taken along the line A-A of Fig. 4A;

Fig. 5 A is a side elevational view of the apparatus in accordance with the invention of

Fig. 4 with the first receptacle, the first cannula and the fitting associated with the

first cannula removed from the first receptacle receiver;

Fig. 5B is a cross sectional side view taken along the line A-A of Fig. 5 A;

Fig. 6 A is a side elevational view of the first embodiment of the apparatus in accordance

with the invention of Fig. 5 including a syringe-type aspirator engaging the Luer

fitting at the base of the first receptacle receiver;

Fig. 6B is a cross sectional side view taken along the line A-A of Fig. 6 A;

Figs 7A to 7D are representative depictions of four possible configurations of the

multiple lumens in the second cannula in side elevation and cross-section;

Fig. 8 A is an exploded side elevation of a second embodiment of the apparatus in

accordance with the invention;

Fig. 8B is a cross sectional view taken along the line A-A of the second embodiment of

the apparatus of the invention shown in Fig. 1; Fig. 9 A is a side elevation of the second embodiment of the apparatus in accordance with

the invention in assembled condition;

Fig. 9B is a cross sectional view taken along the line A-A of the second embodiment of

the apparatus in accordance with the invention shown in Fig. 9A;

Fig. 1OA is a side elevation of the second embodiment of the apparatus in accordance

with the invention of Fig. 2 showing a first receptacle engaging the first

receptacle receiver;

Fig. 1OB is a cross-sectional view taken along the line A-A of Fig. 1OA;

Fig. 1 IA is a side elevation of the second embodiment of the apparatus in accordance

with the invention of Fig. 2 showing a first receptacle engaging the first receptacle

receiver and a second receptacle engaging the second receptacle engaging means;

Fig. 1 IB is a cross sectional view taken along the line A-A of Fig. 1 IA;

Fig. 12A is a side elevational view of the second embodiment of the apparatus in

accordance with the invention of Fig. 1 IA with the first receptacle, the first

cannula and the fitting associated with the first cannula removed from the first

receptacle receiver;

Fig. 12B is a cross sectional side view partially cut away taken along the line A-A of

Fig. 12A; Fig. 13 A is a side elevational view of the second embodiment of the apparatus in

accordance with the invention of Fig. 12A including a syringe-type aspirator

engaging the Luer fitting at the base of the first receptacle receiver;

Fig. 13B is a cross sectional side view taken along the line A-A of Fig. 13 A;

Fig. 14A is an exploded side elevation of a third embodiment of the apparatus in

accordance with the invention;

Fig. 14B is a cross sectional view taken along the line A-A of the third embodiment of

the apparatus of the invention shown in Fig. 14 A;

Fig. 15A is a side elevation of the third embodiment of the apparatus in accordance with

the invention in assembled condition;

Fig. 15B is a cross sectional view taken along the line A-A of the third embodiment of

the apparatus in accordance with the invention shown in Fig. 15 A;

Fig. 16A is a side elevation of the third embodiment of the apparatus in accordance with

the invention of Fig. 15A showing a first receptacle engaging the first receptacle

receiver;

Fig. 16B is a cross-sectional view taken along the line A-A of Fig. 16 A; Fig. 17A is a side elevation of the third embodiment of the apparatus in accordance with

the invention of Fig. 14A showing a first receptacle engaging the first receptacle

receiver and a second receptacle engaging the second receptacle receiver;

Fig. 17B is a cross sectional view taken along the line A-A of Fig. 17 A;

Fig. 18A is a side elevational view of the third embodiment of the apparatus in

accordance with the invention of Fig. 17A with the first receptacle, the first

receptacle receiver;

Fig. 18B is a cross sectional side view taken along the line A-A of Fig. 18 A;

Fig. 19A is a side elevational view of the third embodiment of the apparatus in

accordance with the invention of Fig. 18A including a syringe-type aspirator

engaging the Luer fitting at the base of the first receptacle receiver; and

Fig. 19B is a cross sectional side view taken along the line A-A of Fig. 19A.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

The present invention relates to an apparatus and method for transferring a first substance contained in a first container into a second container containing a second substance, mixing the first and second substances and delivering the resulting mixture aseptically to a delivery device. In the following description of various alternative configurations of the apparatus, common elements will be referred to throughout by the same reference numerals for the sake of ease of understanding.

Referring first to Figs. 1 A-7D, a first receptacle 56 for use with the present invention contains a liquid substance 60 and includes an upper, generally cylindrically shaped portion 62 including an undercut portion 62a. A second receptacle 58 contains a solid substance (typically a powder) 66 under reduced pressure or partial vacuum conditions, and includes an upper, generally cylindrically shaped portion 68 having an undercut portion 68a. The generally cylindrical portions 62 and 68 closely fit within first and second receptacle receivers 14 and 12, respectively, as will be discussed in further detail below. The receptacles 56 and 58 are contemplated to be of conventional, commonly commercially available construction including a seal or stopper, 64 and 70, that seals the open upper end of the generally cylindrically shaped upper portion, 62 or 68, of the receptacle 56 or 58. The seals or stoppers 64 and 70 may be formed entirely of polymeric material suitable for the formation of a closure of the central portion of the open ends of the containers 56 and 58 that may be pierced with a needle or other thin pointed element. Alternatively, a plastic or metal cap portion defining a central opening (not shown) could be used to clamp a pierceable membrane across the open end of each of the receptacles 56, 58. As particularly shown in Figures 2 A and 2B, a first preferred embodiment of the apparatus of the invention includes a main body 10 and receptacle receivers, 12 and 14, extending outwardly from opposite ends of the body 10. The receptacle receivers, 12 and 14, are hollow cavities formed by peripheral walls 16, 18 that may define a plurality of circumferentially spaced longitudinal slits, generally indicated at 20 or 22, extending from the outer peripheral edge of each receptacle substantially all the way to the adjacent end of the main body 10. Accordingly, each portion of the peripheral wall of the receptacle can flex outwardly about its attachment to the main body 10. Also, receptacle locking members in the form substantially radially inwardly extending ridges, 24 and 26, are located substantially adjacent to the outer edges of the wall portions 16, 18 defining the receptacle receivers, 12 and 14, respectively. These locking members in conjunction with the flexibility of the wall portions allow the receptacle receivers, 12 and 14, to securely engage the upper portion of the receptacles 56 and 58 adjacent their open ends 62, 68. For example, a flange formed as part of the receptacles at undercut portions 62a and 68a, a flange formed as part of a stopper (not shown), the lower edge of a membrane clamping cap screwed or friction fit to the open end of each receptacle (not shown) or some other convenient construction that acts to releasably receive the radially inwardly extending projections from the peripheral wall portions of the receptacle receiver into which the particular receptacle is inserted. Hence, it will be clear to those skilled in the art that the open ends 62, 68 of receptacle receivers, 12 and 14, can have the same or different diameters according to the size(s) of the open receptacle receivers provided.

As shown in the various Figures (particularly, Fig. 2B), a second piercing cannula 34 extends from the main body 10 so as to protrude into the second receptacle receiver 12. The second piercing cannula 34 defines multiple (here 2) internal lumens; specifically transfer lumen 36 and venting lumen 38. Also, extending from the main body 10 so as to protrude into the first receptacle receiver 14 is a substantially cylindrical, hollow, connecting portion 40. The transfer lumen 36 is aligned and communicates with the first connecting portion 40 via a first passageway 72 extending substantially along the longitudinal axis of the main body from its first end to its second end. The venting lumen 38, on the other hand, communicates with a side opening 42 in the peripheral surface of the main body 10 via a second passageway 47.

In the preferred embodiments shown in the attached drawings, a first filter 44 is located between the transfer lumen 36 and the first connecting portion 40 internally of the main body 10. Specifically, the first filter 44 is disposed adjacent the base of the first receptacle receiver 14 so as to extend across the first passageway 72 and also across the base of the hollow interior of the substantially cylindrical connecting portion 40. In addition, a second filter 46 is disposed across the second passageway 47 at the inner end of the side opening 42.

A closure member 48 (such as the rubber cap depicted in the drawings) is removeably inserted into the side opening 42. The closure member 48 acts to substantially preserve a pressure difference between the reduced pressure interior of the second receptacle 58 and the interior of the first receptacle 56 during their connection with one another and the transfer of the first substance from the first receptacle to the second receptacle, as will be described more fully below. The closure member 48, however, is removable from the side opening 42 to allow air to flow through the venting lumen 38 and into the second receptacle 58 during the aspiration of the mixed substances from the second receptacle, also as will be described more fully below.

A first piercing cannula 50 is connected to the first connecting portion 40. As will be apparent from the drawings, the first piercing cannula 50 includes a piercing outer end, an internal lumen 52, a plurality of sharp features 51 adapted secure an inner end of the piercing cannula to the outer surface of the seal 64 of a first receptacle 56 mounted in the first receptacle receiver 14, and connecting elements 54a and 54b forming part of a fitting for attaching the first piercing cannula to said first connecting portion 40. As will become more apparent below, the sharp features 51 are thin, substantially planar members that are aligned substantially parallel with the longitudinal axis of the first piercing cannula so as to extend radially outwardly therefrom adjacent to the portion thereof connecting the cannula to the projecting portion 40. These sharp features 51 are adapted to pierce the seal 64 of the receptacle 56 inserted into the first receptacle receiver 14 adjacent to the opening therein formed by the cannula 50 when the cannula 50 is fully inserted into the receptacle receiver 14. These sharp features 51 establish a secure, non-rotatable attachment of the cannula to the pierced seal 64 (see, Figs. 3B and 4B).

Hence, it will be understood that the first connecting portion 40 is preferably provided in the form longitudinally extending, hollow, cylindrical projection into the first receptacle receiver 14 from the adjacent end of the main body 10, while the connecting elements 54a and 54b form a Luer connector adapted to mate respectively with the exterior and interior of the connecting portion 40. Specifically, as shown in Figures 2B, 3B and 4B, connecting element 54b defines a longitudinal opening that communicates with the lumen of the first cannula 50 and is inserted into the hollow portion of the connecting portion 40, while threads located on the connecting portion 54a engage a threaded portion on the outer surface of the connecting portion 40. In other words, the first piercing cannula 50 includes a fitting at its inner end having a central portion that frictionally engages the interior of the connecting portion 40 in telescoping relation therewith, while an outer portion thereof screws onto the connecting portion 40 in engagement with its outer surface. In this regard, it will be understood that the threads on the outer surface of the connecting portion 40 are configured such that they also mate with fittings on various aspirators such as those having connectors of the type found on conventional and readily commercially available needleless syringes and the like (see, for example, Fig. 6B). Accordingly, as shown in Figs. 3A and 3B, the first piercing cannula 50 is adapted to extend into the first receptacle 56 through its seal when the first receptacle is mounted in the first receptacle receiver 14. The first receptacle 56 includes a container portion that is filled with a first substance, typically a liquid substance 60 as shown in the drawings, and an upper, generally cylindrical shaped portion 62 that is sealed by an elastomeric plug or the like 64 as described above. Receptacle 56 is of a type that is of conventional construction and is readily commercially available, usually as the container in which the substance is packaged by its manufacturer or distributor. In use, therefore, the first piercing cannula 50 pierces the seal 64 to open communication between the container portion of the receptacle 56 and the hollow interior of the connecting portion 40 and thence to the first passageway 72 through the main body 10 as the receptacle is inserted into the first receptacle receiver 14.

Further, as shown in Figure 4A and 4B, the second receptacle 58 mates with the second receptacle receiver 12. As mentioned above, the second receptacle 58 includes a container portion that typically contains a powdered, solid substance 66 under reduced pressure or vacuum conditions, and an upper, generally cylindrical shaped, open topped portion 68 that is sealed by a sealing member 70. Receptacle 58 is also of conventional construction and is readily commercially available. In use, the second piercing cannula 34 pierces the sealing member 70 to open communication between container portion of the receptacle 58 and the first passageway 72 through the main body 10 as the second receptacle is inserted into the second receptacle receiver 12.

There are various possibilities with regard to the configuration of the interiors of the hollow cavities defined by the receptacle receivers 12 and 14. For example, the present invention can function with or without the peripheral walls that surround the piercing cannulas 34 and 50, respectively. In addition, the receptacle receiverl2 can have depth that is larger or smaller than the length of piercing cannula 34 and/or the receptacle receiver 14 can have a depth that is larger or smaller than the combined assembled length of piercing cannula 50 and connecting portion 40. It is preferred, however, that peripheral walls 16, 18 are provided, and that those walls exceed the length of cannulas 34 and 50 respectively so as to shield the pointed tips of the cannulas from the surrounding environment and protect users from needlepoint injury.

In addition, there are various possibilities with regard to the opening of lumens, 36, 38 and 52, individually or collectively. For example, Fig 7 A shows the piercing cannula 34 with venting lumen, 38, opening on the side; Fig 7B shows the piercing cannula 34 with transferring lumen, 36, opening on the side; Fig 7C shows the piercing cannula 34 with both venting and transferring lumens, 36 and 38, openings on the side; and Fig 7D shows the piercing cannula 50 with internal lumen, 52, opening on the side. Accordingly, it will be recognized by those skilled in the art that the positions of the lumen openings are a matter of design choice that can vary along the lengthwise direction of the piercing cannula, 34 or 50 according to the dictates of the remainder of the structure into which they are to be incorporated.

There also are various possibilities with regard to the disposition of the side opening 42 relative to the remaining portions of the apparatus. For example, Fig 2 shows side opening 42 entering the sidewall of the main body 10 substantially perpendicularly to the longitudinal axis of the main body 10. However, the side opening 42 can be disposed at an angle other than perpendicular to the longitudinal axis of the main body 10 without departing from the present invention in its broadest aspects. In fact, the side opening 42 does not have to enter the sidewall of the main body at all. Instead, the side opening may be defined by projections extending outwardly from the side wall of the main body that form a cavity adapted to hold the closure member, the cavity being in communication with the second receptacle receiver 12 via the second passageway 47 through the main body 10 and lumen 38 in the cannula 32. The configuration of the various filters in the apparatus also can be varied without departure from the present invention. Accordingly, while Fig 2 shows a preferred embodiment that utilizes the three filters, 44, 32 and 46, alternative embodiments of the present invention can have none, one, or any combination of two of the three filters discussed above without departure from the present invention in its broadest aspects. Furthermore, other alternative embodiments could include more than the three filters of the preferred embodiment discussed above and/or any combination thereof.

The specific nature of the sharp feature 51 also is variable without departure from the present invention. Thus, while as shown in Fig 2 the preferred embodiment discussed above uses plurality of fin-like elements that partially pierce the seal 64, alternative configurations (not shown) such as a single fin, a spike, a plurality of spikes, and the selection of the material of the piercing cannula 50 such that it will generate enough friction with the sides of the pierced opening in the seal to hold the position of the cannula fixed relative to the seal, all such that the first piercing cannula 50 will turn so as to disengage the fitting 56a, 56b from the connecting portion 40 protruding from the main body 10 when the first receptacle 56 is rotated are contemplated within the scope of the present invention in its broadest aspects.

In addition, there are various possibilities with regard to the connecting means, 40, 54a and 54b. Fig 2 shows the preferred Luer type connection, but any means that can connect the piercing cannula 50 with the connecting portion 40 in a functionally equivalent manner are equally applicable as alternative embodiments of the present invention.

Examples of additional alternative preferred embodiments are shown in Figs. 8A-13B and 14A-19B, respectively. Thus, as shown in Figs. 8 A - 13B, the fitting 100 adapted to mount the first cannula 50 onto the cylindrical hollow portion 40 in the first receptacle receiver 14 may include a handle 102 extending substantially radially outwardly from the fitting through a slot 104 in the peripheral wall of the first receptacle receiver 14 to an outer handle end 106. hi this case, the longitudinal slots in the peripheral wall of the second receptacle receiver 12 are retained, but in the first receptacle receiver 14 the slot 104 replaces those longitudinal slots. Slot 104 extends in a spiral generally indicated at 107 in Fig. 12A toward the main body 10 from an inner end 108 of a longitudinal slot 110 that extends from the outer edge of the peripheral wall a preselected distance toward said main body 10. This construction permits movement of the handle 100 from a closed end 112 of the spiral slot 104 when the fitting 100 fully engages the hollow cylindrical connecting portion 40 in the first receptacle receiver 14 along the spiral slot 104 in a manner that acts to unscrew the fitting 100 from the cylindrical hollow connecting portion 40. The thread pitches of the engaged fitting 100 and the exterior of the hollow cylindrical connecting portion 40 are matched with the pitch of the spiral of the slot 104 in the peripheral wall of the first receptacle receiver 14 such that when the handle 102 reaches the inner end 108 of the longitudinal slot 104 (i.e., the inner end of the longitudinal slot portion), the fitting is fully released from its threaded engagement with the hollow, cylindrical connecting portion 40. Hence, the fitting 100, the first cannula 50 and the first receptacle 56 can be removed from the first receptacle receiver 14 together with the assistance of the handle portion 102 guided outwardly through the longitudinal slot portion 110 of the slot formed in the peripheral wall of the first receptacle receiver 14.

In another configuration, shown in Figs. 14A - 19B, the peripheral wall of the first receptacle receiver may include circumferentially spaced, longitudinal slots as described above or the spiral slot just described, while the peripheral wall of the second receptacle receiver 12 defines instead of the above-mentioned longitudinal slots, an inwardly extending projection adjacent to its outer edge and a slot 200 (See Fig. 16A) that includes a portion 202 that extends longitudinally toward the main body from its outer edge to one end 204 of a substantially circumferentially disposed slot 206 that extends approximately one-halfway around the circumference of the second receptacle receiver 12. In this alternative construction, a second receptacle 58 defining a projection receiving portion adjacent to its sealed open end (such as an edge of a cap) may be easily, yet securely, inserted into the second receptacle receiver 12 by virtue of the resilient movability of the outer circumferential portion 208 (see, Fig. 15A) of the peripheral wall of the second receptacle receiver located between the circumferentially extending slot 206 and the outer edge of the peripheral wall. This construction facilitates the secure, yet removable, disposition of a second receptacle 58 in the second receptacle receiver 12 particularly in those cases in which it is important to load the second receptacle receiver quickly so as to avoid liquid loss from the first receptacle 56 and to maintain the reduced pressure in the second receptacle 58 for drawing the first substance into the second receptacle through the first passageway 72 through the main body 10.

Furthermore, there are various possibilities with regard to the configurations of the interiors 16 and 18 of the first and second receptacle receivers 12 and 14. Fig 2 shows the receptacle receivers as having a circular cross-section, however, in permissible alternative embodiments, the interiors of the receptacle receivers can have cross sectional shapes other than circular, including oval, square, rectangular or other closed shapes.

The operation of the present invention now will be discussed with reference to the preferred embodiments depicted in the drawings (which are similar in this regard as between Figs. 1A - 6B, 8A - 13B and 14A- 19B). When using the present invention, the first piercing cannula 50 is attached to the main body 10 in the manner generally shown in Figs. 2A - 3B. Also, the closure member 48 is used to tightly seal the side opening 42 of the main body 10 in the manner shown in Figs. 2 A - 3B. The assemblage thus formed is interconnected with the first receptacle 56 in the manner shown in Figure 3. The first receptacle receiver 14 receives the first receptacle 56 securely with the first locking member 26 engaging the upper portion 60 of the first receptacle 56. This assemblage, that at this stage comprises the first piercing cannula 50, the main body 10, the closure means 48, and the first receptacle 56, is mated with the second receptacle 58 in the manner generally shown in Figs. 4A -4B. The substance in the second receptacle 58 as previously mentioned is under reduced pressure or vacuum. Therefore, when the second piercing cannula 34 pierces the seal 70 of the second receptacle 58, the liquid substance in the first receptacle 56 will be automatically and rapidly drawn into the container portion 66 of the second receptacle 58 in the manner indicated in Figs. 4A — 5B. As the liquid substance travels from one receptacle to the other, particulates that may be contained in the liquid substance or generated otherwise (for example, by the engagement of features 51 with the seal 64 of the first receptacle 56, will be prevented from entering into the container portion 66 of the second receptacle 58 by the first filter means 32 in the piercing cannula 50.

Once all the liquid substance has been drawn into the container portion 66 of the second receptacle 58, and the liquid substance and the solid substance is thoroughly mixed, the first receptacle 56 along with the first piercing cannula 50 is disconnected from the main body 10 as generally indicated in Figs. 5 A and 5B. The presence of sharp features 51 ensures that the first piercing cannula 50 disengages from the main body 10 as the first receptacle 56 is axially rotated as discussed above. Then, to transfer the mixture out of the second receptacle 58, an aspirating means 76 is attached to the connecting portion 40 as discussed above. As generally indicated in Figure 6, the aspirating means 76 is a needleless syringe assembly that is threadably connected the main body 10. The closure member 48 is removed from the opening 42 in the sidewall of the main body 10 so as to expose one end of the second passageway 47 which in turn is connected to the venting lumen 38 of the second piercing cannula 34 with filter means 46 attached. The aspirator or syringe 76 then is used in a conventional manner to withdraw the mixture from the container while the venting lumen and second passageway equalize the pressure in the second receptacle with the outside environment in order to avoid the creation of air locks in the first passageway 72. Finally, the aspirator 76 is disconnected from the assemblage by unscrewing its fitting from the connecting portion 40 as generally shown in Figure 6, and the mixture is delivered to patient or other desired destination via the aspirator 76.

Accordingly, the reconstitution and transfer device of the present invention solves numerous problems associated with conventional reconstitution and transfer devices. Specifically,

1. by using receptacle receivers, receptacles that contain a liquid substance or a solid substance can be securely connected with the apparatus of the present invention, thereby simplifying the mixing and transfer operation;

2. by using receptacle receivers wherein piercing cannulas are shielded by peripheral walls from operators, needlestick injuries are effectively eliminated during reconstitution and transfer operations;

3. by incorporating filter means at various strategic locations in the apparatus (a) particulates or contaminants from liquid substances are prevented from entering into the second receptacle containing the solid substance, (b) particulates or contaminants generated, within the apparatus are prevented from entering into the mixing receptacle, and (c) particulates or contaminants from the intermixed solution are prevented from entering into the aspirator, whereby patient complications introduced by contamination are avoided; and 4. by using fixed and optimized piercing cannulas in the apparatus, proper dosage levels of medicinal preparations and the like are ensured.

The above description of the preferred embodiments of the present invention contains many specifications and details, however, it is to be understood that these specifications and details are to be construed only as exemplifications of the presently preferred embodiments thereof and not as limitations upon the scope of the present invention in its broadest aspects. Numerous other alterations, variations, modifications and the like are deemed to be possible with the teachings of the present invention in its broadest aspects. Accordingly, the scope of the present invention is to be determined solely by the appended claims and their legal equivalents.

Claims

We therefore claim:

1. An apparatus for mixing a first substance contained within a first receptacle with a second substance contained under reduced pressure within a second receptacle, said first and second receptacles each respectively defining a sealed opening, and for facilitating a transfer of the resultant mixture to an aspirator, said apparatus comprising: a main body portion having a peripheral surface, and opposing first and second ends, said main body portion defining a first passageway connecting said first end to said second end and a second passageway connecting said second end to said peripheral surface; a first receptacle receiving portion at said first end of said main body and a second receptacle receiving portion at said second end of said main body, said first and second receptacle receiving portions being adapted to receive and releasably hold said sealed open ends of said first and second receptacles respectively; a first piercing cannula removeably connected with said main body portion adjacent said first end thereof and extending into said first receptacle receiving portion, said first cannula being adapted to pierce a seal located on a portion of a receptacle inserted into said first receptacle receiver and defining a longitudinal lumen connecting an outer piercing end of said first cannula with said first passageway, a second piercing cannula extending from said second end of said main body into said second receptacle receiving portion, said second cannula being adapted to pierce a seal located on a portion of a receptacle inserted into said second receptacle receiver and defining a pair of lumens, one of said lumens connecting an outer piercing end of the second cannula with said first passageway, and the other of said pair of lumens connecting the interior of said second receptacle receiver- with the surrounding atmosphere through said second passageway; and closure means removeably associated with said second passageway at said peripheral surface of said main body; whereby said first substance contained within said first receptacle may be transferred into said second receptacle containing said second substance and the resultant mixture may be removed from said second receptacle via said first passageway when said closure member is removed from said second passageway and said first receptacle and said first cannula are removed from said first receptacle receiver.

2. The apparatus of claim 1 further comprising a sterile air filter extending across said second passageway.

3. The apparatus according to claim 1 wherein a first particle capturing filter extends across the lumen of said first cannula.

4. The apparatus according to claim 3, wherein a second particle capturing filter extends across said first passageway.

5. The apparatus of claim 1 , wherein said first and second receptacle receivers respectively include a peripheral wall portion defining a plurality of circumferentially spaced longitudinal slots and inwardly extending projections adjacent an outer edge thereof for releaseably retaining an open end of one of said receptacles therein.

6. The apparatus of claim 1, wherein said first receptacle receiving portion defines a hollow connecting portion surrounding a longitudinal projection of said first passageway and having a threaded external surface, and wherein said first cannula is mounted in a fitting adapted to screw onto said cylindrical portion, said fitting defining a plurality of radially extending projections substantially adjacent a location at which said cannula enters said fitting, said plurality of projections being adapted to pierce a seal of a receptacle inserted into said first receptacle receiving portion adjacent to the location at which said cannula pierces said seal such that axial rotation of said first receptacle causes said projections to bear circumferentially on said seal so as to unscrew said fitting from said hollow connecting portion whereby said first receptacle, said first cannula and its associated fitting can be easily removed from said first receptacle receiving portion together.

7. The apparatus of claim 1 , wherein said first receptacle receiving portion defines a hollow connecting portion surrounding a longitudinal projection of said first passageway and having a threaded external surface, and said first cannula is mounted in a fitting adapted to screw onto said cylindrical portion, said fitting including a handle extending substantially radially outwardly from said fitting through a slot said peripheral wall of said first receptacle receiving portion that extends in a spiral toward said main body from an inner end of a longitudinal slot that extends from the outer edge of said peripheral wall a preselected distance toward said main body, whereby movement of said handle from a closed end of said spiral slot along said spiral slot unscrews said fitting from said connecting portion such that when said handle reaches said inner end of said longitudinal slot, the fitting is released from the connecting portion and the fitting, the first cannula and the first receptacle can be removed from the first receptacle receiving portion together. aratus of claim 1 wherein said peripheral wall of said second receptacle receiving portion defines an inwardly extending projection adjacent to its outer end and a slot that extends longitudinally toward said main body from its outer edge to one end of a circumferentially disposed slot extending approximately half way around the circumference of said second receptacle receiving portion, whereby a second receptacle defining an outwardly extending projection adjacent to its sealed open end may be easily, yet securely, inserted into the second receptacle receiving portion by virtue of the resilient movement of an outer circumferential portion of said peripheral wall disposed between said circumferentially extending slot and said outer edge of said peripheral wall of said second receptacle receiving portion.

An method for mixing a first substance contained within a first receptacle with a second substance contained under reduced pressure within a second receptacle, said first and second receptacles each respectively defining a sealed opening, and for facilitating a transfer of the resultant mixture to an aspirator, said method comprising the steps of: providing a main body portion having a peripheral surface and opposing first and second ends, said main body portion defining a first passageway connecting said first end to said second end and a second passageway connecting said second end to said peripheral surface; a first receptacle-receiving portion at said first end of said main body and a second receptacle receiving portion at said second end of said main body, said first and second receptacle receiving portions being adapted to receive and releasably hold said sealed open ends of said first and second receptacles respectively; a first piercing cannula removeably connected with said main body adjacent said first end of said main body and extending into said first receptacle receiving portion, said first cannula defining a longitudinal lumen connecting an outer piercing end of said first cannula with said first passageway, a second piercing cannula extending from said second end of said main body into said second receptacle receiving portion, said second cannula defining a pair of lumens, one of said pair of lumens connecting an outer piercing end of the second cannula with said first passageways and the other of said pair of lumens connection the interior of said second receptacle receiver with the surrounding atmosphere through said second passageway; and closure means removeably associated with said second passageway at said peripheral surface of said main body, inserting a sealed end of said first receptacle into said first receptacle receiver such that said first cannula pierces the sealed end of said first receptacle and said first receptacle is releasably held in said first receptacle receiving portion; and thereafter inserting a sealed end of said second receptacle into said second receptacle receiving portion such that said second cannula pierces the sealed end of said second receptacle and said second receptacle is releasably held in said second receptacle receiving portion, whereby said first substance is transferred from said first receptacle into said second receptacle through said first passageway under the applied drawing force of the reduce pressure in said second receptacle; opening said closure means; removing said first cannula and said first receptacle together from said first receptacle receiver; and attaching said aspirator to said first passageway at said first end of said main body and aspirating the mixed first and second materials from said second receptacle.