SYSTEM FOR THE STERILE MIXING OF MATERIALS

Abstract: A rigid or collapsible vial (12) defining a mouth portion (18), and a closure sealingly occluding the mouth portion, may carry a first and typically solid material (16) in sterile, sealed relation. A conduit member (24) is carried by the vial in sealing manner and comprises a connector member (26) for providing sealed connection with a corresponding connector member (28). Each connector member comprises transparent housing means (32) and a thermoplastic opaque wall portion (34) positioned as part of the wall of the housing, in such a manner that the respective opaque wall portions may be brought together into facing contact as the two housings are brought together. As a result of this, upon exposure of the connected housings to radiant energy, the opaque wall portions in facing contact can fuse together and open an aperture through the opaque wall portions to provide connection between the interiors of the respective housings. The second housing may communicate with a second, generally collapsible and flexible container (14) which may contain typically a diluent for the material in the vial, so that the diluent may mix with the first material in the vial in aseptic, sterile manner permitting longer term storage of the combined mixture.

Description: SYSTEM FOR THE STERILE MIXING OF MATERIALS BACKGROUND OF THE INVENTION In parenteral solution therapy, supplemental medica¬ tion is often added to the patient along with the bulk solutions. This may be conveniently done, for example, by means of the ADD-A-LINE and the CONTINUFLO sets for parenteral solution administration sold by Travenol Laboratories, Inc. of Deerfield, Illinois, and described, for example, in U.S. Patents 4,034,754 and 4,105,029. Accordingly, materials such as antibiotic may be administered at the physician's option on an intermittent basis during intravenous solution treatment by means of a connection into the main intravenous solution line communicating with the venous system of the patient, or on a continuous basis by addition to the bulk solution. In a large hospital operation, it of course would be desirable to have the supplemental medicament materials ready in their liquid, diluted form for immediate ad¬ ministration at the option of the physician. However, many of these materials must be stored in the dry form until immediately before use, particularly because of the danger of contamination through bacterial growth, or lack of pharmaceutical stability, which may result when the liquid or dry medicament is mixed or reconsti¬ tuted by adding a diluent a substantial period of time before its administration. In accordance with this invention, a sterile system is provided in which liquid or dry medicament materials or the like may be mixed or reconstituted with a sterile diluent at a convenient time substantially prior to the time of use, while at the same time retaining the re- liable, sterile seal of the system so that multiplication of bacteria in the system is not a problem. As a result of this, fluid or dry medicaments and the like can be mixed or reconstituted with diluent in a hospital phar¬ macy, for example, at a convenient slack period time, and stored for use at a future date. Then, when the medicament is needed, it is ready in liquid form for immediate us . without having to go through the time-con¬ suming effort of reconstituting the material with diluen at the time when it is needed. DESCRIPTION OF THE INVENTION In accordance with this invention, a vial is pro¬ vided which comprises a self-supporting body defining a mouth portion, and a closure sealingly occluding the mouth portion. The closure carries in sealing manner a conduit member which comprises a connector member for providing sealed communication between the connector member and a corresponding connector member. The connector member comprises transparent housing means, and a thermoplastic, opaque wall portion positioned as part of the wall of the housing means. Means for connecting the housing means to a housing means of an¬ other connector member having a corresponding thermo¬ plastic wall portion are provided so that the connection may be made between the housings in such a manner as to bring the respective thermoplastic wall portions to¬ gether into facing contact. As the result of this, upon exposure of the con¬ nected housings to radiant energy, the thermoplastic wall portions in facing contact can fuse together and open an aperture through said opaque wall portion, to provide a connection between the interiors of the respective hous¬ ings. The inventive principle of the sterile connector means which is utilized in this invention is as described in the Granzow, et al. U.S. Patent No. 4,157,723, as well as the Am ann, et al. Patent Application Serial No. 005,749, filed January 23, 1979, and Boggs, et al. Patent Application Serial No. 027,575, filed April 6, 1979. The principle utilizes the concept, as described therein, that the transparent sealed housings permit the passage of radiation such as visible light or infrared radiation, while the abutting, opaque membranes absorb the infrared radiation and heat to their melting or softening point, whereby the two thermoplastic wall portions fuse together and form an aperture by the flow of molten material of the membrane so that the two membranes seal together about the aperture into a com¬ mon mass. While it is presently preferred for both of the thermoplastic wall portions to be opaque to the particu- lar radiant energy used, it is contemplated as an alter¬ native technique for only one of the thermoplastic por¬ tions to be opaque, while the other thermoplastic wall portion of the housing means of another connector member may be transparent. In fact, such a housing means of the other connector, carrying a transparent, thermoplast wall portion, could in some circumstances be opaque in its own right, with the hole-opening function between the abutting thermoplastic wall portions being effected by the absorption of radiant energy by the opaque, therm plastic wall portion through the transparent housing, with conduction of heat from the opaque wall portion to the abutting transparent thermoplastic wall portion. It is generally currently preferred to select a predominantly crystalline plastic material for the thermoplastic wall portions as described in the above- cited Boggs, et al. patent application, for example, a carbon-filled poly(4-methyl-l-pentene) which is sold under the name TPX by Mitsui Chemical Company. Such materials may preferably have a crystalline melting point of above 200 C. Accordingly, the fusing and hole-opening step can provide indication that the walls of the newly-formed aperture through the abutting opaque membranes have been exposed to a sterilizing temperature, giving a highly reliable indication of the formation of a sterile con¬ nection. As the result of this, the diluent can pass to the vial to reconstitute the dry medicament with firm re¬ liability that sterility has not been breached, despite the formation of a new connection between the two con¬ tainers. As one embodiment of the vial of this invention, a generally rigid bottle member may define a mouth portion ' A O.V. , ^ i * 1J and may carry a puncturable, resealable stopper means re¬ tained in the mouth portion. The connector member may be carried in this instance by a tubular cannula defining an inwardly-pointed spike adapted to penetrate the punctur- able stopper means. A flexible seal such as a flexible boot member may be sealed to the mouth of the vial at one end, being sealed to the cannula, for example at an intermediate point thereof, to permit manual penetration of the cannula through the stopper means. This provides a double sealed configuration in which the contents of the container are also sealed from the conduit and the connector member until the spike penetrates the stopper means. Accordingly, sterile connection may be first made between the connector member and its corresponding con¬ nector member of another container, and then final, sterile access to the vial contents may be obtained by pushing the spike through the stopper means. As an alternative con iguration to the above, the conduit member of the vial which defines the connector member may also define, adjacent its other end, a closed end wall sealed within the closure. Means are then pro¬ vided for rupturing the conduit member to open the other end upon manual manipulation thereof from the outside. This sort of structure may include a cannula capable of being pushed through a membrane in the manner similar to the "Cell-Proof" closure on many Blood Packs® sold by the Fenwal division of Travenol Laboratories, Inc. Specifically, the closed end wall described above may be openable by means of a projecting member which extends outwardly from the closed end wall. Accordingly, when the closure is relatively flexible, manual bending of the projecting member can cause rupture of the end wall to permit the opening of the conduit member. This structure may be similar to structures as defined in Bayham U.S. Patent Application No. 876,790, filed February 10, 1978. As a further alternative, the vial in accordance with this invention may define a body which is self- supporting of its shape, but sufficiently resilient to be manually collapsible. The container may, for exampl comprise a shoulder member to which a semi-rigid, cup- shaped member is sealed. As a further embodiment, the vial utilized in this invention may have a body which defines a plurality of bellows-like convolutions so that the vial, which is ma of semi-rigid material, may be manually collapsed by flexing of the convolutions. As a further alternative, a separate adaptor may b provided for sterile connection between the interior of a vial which defines a mouth portion and a closure in¬ cluding a puncturable membrane. This adaptor may be used to adapt any vial for sterile connection with an¬ other container. The adaptor defines a cannula member including a pointed rear end, and a forward end which defines the connector member as previously described, for providing sealed connection with a similar connector member. Alt natively, a flexible, collapsible container equipped with a sterile connector as disclosed herein may be use independently and apart from the vial, for connection with another container such as another flexible, col- lapsible container utilizing the structures and methods as disclosed and claimed herein. In the drawings, Figure 1 is an elevational view of a supplemental medication administering system in ac¬ cordance with this invention, in which a vial and a fle ible, collapsible container are linked together in sterile connection. Figure 2 is an elevational view showing, how the flexible collapsible container of Figure 1, after having dissolved and received the dry, solid contents of the vial, may be connected to a supplemental medication ad¬ ministration set positioned in connection with a conven¬ tional administration set for parenteral solution. Figure 3 is a vertical sectional view of one embodiment of a vial which may be utilized in accordance with this invention in the connected system of Figure 1. Figures 4, 5 and 6 are vertical sectional views showing alternative embodiments of vials which may be used as a substitute for the vial of Figure 3. Figure 7 is a detailed, fragmentary elevational view of a bag similar to Figure 1, but using the connector of Figure 6. Figure 8 is a perspective view showing how the closed system of Figure 1 may be manipulated after opening of the connection between the two containers shown to re¬ move liquid from container 12. Referring to the drawings, Figure 1 shows a supple¬ mental medication administering system 10 in which a vial 12 is provided in sterile connection with a flexible, col¬ lapsible container 14, which may be generally similar in construction to the Mini-Bag sold by Travenol Laboratories, Inc., of Deerfield, Illinois, modified as described here¬ in. Vial 12, on the other hand, may be similar to con- ventional dosage ampules except for the modifications described below. Vial 12 may typically contain a liquid or solid medicament material 16, and may further define a closure 20 for sealingly occluding mouth portion 18. Closure 20 may further include a latex needle -pierceable stopper 22 (Figure 3) , and may carry in sealed manner a conduit member 24 which includes at its outer end a connection member 26 for providing sealed connection between itself and a corresponding connector member 28, which is carried on the end of conduit 30 in sealed relation with collaps¬ ible bag 14. Connector members 26, 28 may be of a design as specifically described in Patent No. 4,157,723, or the Ammann, et al. or Botts, et al. patent applications previously cited, each preferably comprising a transparent housing means 32, and a thermoplastic, opaque wall portion 34 , positioned as part of the wall of the housing means 32. Connecting means 36 are provided for connecting the respective connectors 26, 28 together, with the respecti opaque walls 34 being broughttogether into facing con¬ tact. Accordingly, sterile connection is achieved as previously described by exposing the connected housings to radiant energy such as infrared radiation, so that th opaque wall portions in facing contact can fuse together and open an aperture through the opaque wall portions to provide a sterile connection between the interiors of the respective housings without disconnection thereof. This provides of course a connection between containers 12 and 14, permitting diluent, for example, in bag 14 to flow into contact with the solid, dry material 16 of vial 12. The system may be agitated by shaking without opening, and then the liquid contents, carrying dissolve or suspended material 16, may be allowed to flow back into bag 14. If the contents 16 are liquid, they can directly flow into bag 14. Conduit member 24, carried by connector member 26, may carry a sharpened point or spike 58 at its end so that, after connection and opening between connector members 26, 28 has been made, a further connection bet¬ ween the contents of the vial 16 can be opened by the point 58 penetrating through stopper 22. Correspondingly, as shown in Figure 7, connector member 28a, mounted on bag 14, may correspondingly carry a hollow pointed spike member 37, which, in turn, is connected to conduit 30 of bag 14, by means of a flexibl tubular boot member 39. Positioned within conduit 30 is a tubular member 41 which carries a needle-pierceable diaphragm 43. Accordi ly, after the sealed connection has been made between connector member 28a and another connector member on a vial such as vial 12, spike member 37 may be advanced to penetrate diaphragm 43, which is possible because of the presence of flexible boot 39, so that an open channel is formed between the inside of vial 12 and the interior of bag 14. Alternatively, spike member 37 and diaphragm 43 may be replaced, if desired, by a breakaway projecting member extending outwardly from a closed end of a tubular structure analogous to spike member 37, in a manner similar to that shown in Figure 4. Following this, flexible tubing 30, which may be made of a heat sealable material such as polyvinyl chloride plastic, may be clamped or preferably heat sealed to provide a sealed end 38 to bag 14, and the tubing 30 outside of the sealed end may be severed to get rid of vial 12 and the connectors 26, 28. At this point, the contents of bag 14 remain reliably sterile, and may be stored for a period of time which is con¬ siderably lower than in the case where a conventional, aseptic connection between containers 12 and 14 has been made. When the time arrives for use of the liquid con¬ tents, containing the material 16 such as a powdered antibiotic, •an aseptic connection may be made through added conventional sealed port 40 in bag 14 by means of supplemental medication set 42, for example, which may be of the type previously described and sold by Travenol Laboratories, Inc. Supplemental medication set 42 may, in turn, be connected to a Y-site 44 of an ap- propriate administration set 46 such as the ADD-A-LINE set described above. The set may be connected with a conventional parenteral solution container 48; the set primed; and the set needle 50 may be inserted into the venous system of the patient as shown in Figure 2. By this technique, conventional parenteral solu¬ tion administration may be provided to the patient by appropriate adjustment of roller clamp 52. In use, flexible container 14 is generally set at a vertically higher level than container 48. Accord- ingly, when clamp 54 is opened, the contents of con¬ tainer 14 preferentially flow into set 46, and into the patient's venous system through needle 50, for immediate administration of supplemental medication. When the JD'.PI Ar- V. ' iPO contents of bag 14 are exhausted, or clamp 54 is closed, the normal flow of liquid from parenteral solution con¬ tainer 48 may be resumed. Turning to the details of vial 12, the generally rigid bottle member 54 shown in Figure 3 includes, as stated, the puncturable resealable stopper means 22 re¬ tained in mouth portion 18 by a ring retention means 56, comprising a crimped metal ring of conventional design. Conduit member 24 is defined in part by a rigid, tubular cannula which, in turn, defines an inwardly- pointed spike 58 adapted to penetrate puncturable stoppe means 22. A flexible boot member 60 is sealed to the mouth 18 of the vial 12 at one end 62, by clamping actio as shown on the part of ring retention means 56. At its other end, boot 60 is sealed to cannula 24 at area 64. Boot 60 is made of a flexible, elastomeric material so that cannula 24 may be manipulated upwardly and down¬ wardly to cause pointed end 58 to penetrate stopper 22, for communication of cannula 24 with the interior of vial 12 in aseptic manner. Turning to Figure 4, another embodiment of the vial of this- invention is disclosed. Body 66 of the vial of Figure 4 may be self-supporting in its shape, but suf¬ ficiently resilient to be manually collapsible to assist in the expulsion of the contents within body 66. Ad¬ ditionally, the body 66 may have sufficient plastic memory to tend to spring out again into its original shape after manual collapse, if desired, so that the con tainer is capable of exerting gentle suction, for facili tating the filling of body 66 with a diluent or the like. A semi-rigid closure member 68 is sealed to the open end of cup-like body 66 as shown, and defines a flexible tube 70 which is sealed at its outer end 72 to a conduit member 74 in accordance with this invention. The outer end of conduit member 74 may be integrally at¬ tached to a connector member 26a. of similar or identical design to connector member 26 previously described. At its other end from the connector member 26a, conduit member 74 defines a closed end wall 76, sealed within tubing 70, so that its inner end is in communica¬ tion with the interior of body 66 of the vial of Figure 4. Means for rupturing the conduit member 76 are pro- vided, which may constitute a structure similar to the Bayham U.S. Patent cited above. Projecting member 78 extends outwardly from closed end wall 76 of conduit member 74. Tubing 70, constituting part of the closure of the mouth portion of the vial 66 is sufficiently resilient to permit manual bending of projecting member 78 to cause rupture of the end wall 76, to permit the opening of conduit member 74, providing communication between the interior of connector 26a and vial 66. Turning to Figure 5, a vial comprising a flexible body 80 is disclosed, in which the flexible body 80 de¬ fines a plurality of bellows-like convolutions 82 so that the vial may be manually collapsed by flexing of the convolutions, and will tend to spring back to its normal configuration, exerting suction for assisting and re¬ ceiving diluent solution from another container, or the like. As in the embodiment of Figure 4, a closure member 68a is provided, being sealed to the mouth of vial body 80 as shown. The remaining parts including conduit 74a., tubing 70a, projecting member 78a. and connector member 32a, may be identical in structure and function to the corresponding parts of Figure 4. Referring to Figure 6, a vial 84, which may be a conventional rigid glass vial, for example, may contain a rubber stopper 86 as shown, which carries a vertically upstanding rubber sleeve 88 as an integral part of the stopper. Connector member 28a defines a transparent housing 92, having an opaque thermoplastic wall member 94 having a function similar to the previous connector members. Bayonet 96 and aperture 98 are proportioned to lockingly fit in the corresponding aperture and bayonet of a similar housing, for sterile connection in accordance with the principles previously described. Conduit 100 communicates at one end with the chamb 102 which is partially defined by the inner surface of opaque wall member 94. At the other end of conduit 100 an end wall 104 is defined, and a projecting member 106 projecting out from wall 104 and rupturable by bending open wall 104 in a manner similar to that described wit respect to members 78 and 78a in Figures 4 and 5. Accordingly, this vial may be opened, typically after connection of connector member 90 with mating con nector member, attached, for example, to a bag similar to bag 14, by laterally bending connector member 90. Connector member 28a_ can flex laterally because of the presence of sleeve 88, to snap away projecting member 1 by impingement with the inner wall of the vial 84. Pro jecting member 106 then falls to the bottom of the vial. After opening of all of the connections between th vial (such as vial 12 or any of the other vials shown) and bag 14, for example, the flexible bag 14 may be pos tioned in the vertical position as shown in Figure 1, a manually squeezed to force some of the liquid contents the bag 14 through the connection into vial 12. Upon r lease of manual squeezing, bubbles of air or other gas in vial 12 which is compressed by the influx of the liq move upwardly through the connection into bag 14. An¬ other squeeze of the bag 14 provides more liquid, until the desired amount of liquid is transferred. This tech nique may be used in the instance where the contents of the vial connected to bag 14 are solid. The vial 12 (or other embodiment thereof) may then be shaken to dissolve the solid contents. The bag and vial system may then be inverted to the position as sho in Figure 8. In the event that the liquid contents of the vial do not readily flow into bag 14 in a spontaneo manner, bag 14 may be squeezed again to force air or other gas in the bag into vial 12. The air bubbles rise to the top of the vial, and upon release of the pressure on bag 14, the compressed air in vial 12 forces some of the liquid 110 in the vial downwardly back into bag 14. Repeated application of pressure to bag 14 causes more air to pass into vial 12 under pressure, and, upon re¬ lease, the pressurized air forces more of the liquid out until the vial 12 is empty. Thereafter, tubing 30 may be heat-sealed and severed as described previously, and bag 14 may be placed into storage for ultimate use. The above technique for transferring liquid to and from the bag and the vial requires certain dimensional characteristics of the double container system, or the solid and liquid contents will not be completely removable from the vial 12 in the closed system. The parameters of the closed system shown in Figures 1 and 8 therefore preferably meet the following conditions; the air volume (which is intended to include any other gas present) in bag 14 and vial 12 (which is intended to include any design of vial used) must exceed the liquid volume of bag 14 , plus the combined total internal volume of conduits 30 and 24, being the entire volume of the con¬ nection flow path for fluids between bag 14 and vial 12. Furthermore, the air volume of vial 12 must exceed the combined total internal volume of conduits 30 and 24, including the internal volumes of connectors 26,28. It is to be understood, of course, that in the specific instance of Figure 3, the volume of conduit 24 does not include the volume within boot 60 but outside of tubular conduit member 24, since conduit member 24 is positioned in sealed relation within stopper 22. Under the above conditions, when one of the con¬ tainers such as bag 14 is compressible and the other of the containers is such as vial 12 is non-expansible, the above conditions provide a joined container system in which the contents of non-expansible container 12 can be completely removed by, in effect, pumping liquid out of container 12, or from container 14 into container 12 and then back out again. Accordingly, this invention provides a means whereby the sterile contents of a vial may be brought into con¬ tact with a diluent or other ingredient of a formulatio which is desirably mixed without a breach of sterility. By this invention, the reliability of sterility is so high that sensitive materials may be stored for a sub¬ stantial period of time following the mixing, when such would not be advisable if merely normal aseptic tech¬ niques were followed. After such storage, the contents may be administered in any manner desired for any use in or out of the medical field, using one or more of the connected containers as shown herein, or equivalent stru tures. It is also contemplated that vials may be utilized having more than one sterile connector system attached thereto, for connection with a multiplicity of other con tainers of various types as may be warranted by the situ ation. The above has been offered for illustrative purpose only, and is not intended to limit the invention of this application, which is as defined in the claims below.

Claims: AMENDED CLAIMS (received by the International Bureau on 21 April 1981 (21.04.81)) 27. (NEW) An assembly for sealing a port communica ing with the interior of a container to block communication through the port between the interior of the container and the atmosphere, said assembly comprising stopper means adapted for sealing engagement with the container port and including passage means communicat¬ ing with the container interior, a transparent housing means having a hollow in¬ terior and including conduit means communicating with said hollow interior, flexible mounting means carried by said stopper means and circumferentially defining a chamber extending outwardly of and in communication with said passage means, said flexible mounting means being operative for supporting said transparent housing means on said stopper means with said hollow interior disposed outwardly of said chamber and in communication with the atmosphere and said conduit means disposed within said chamber and for further per¬ mitting, in response to external forces, the resilient displacement of said housing means relative to said stopper means in directions axially and transversely of the longitudinal axis of said chamber, and meltable opaque wall means -extending across said outwardly disposed hollow interior of said housing means and being operative for normally sealing said hollow in¬ terior, and thus said chamber, from communication with the atmosphere and for forming, in response to the subsequent application of radiant energy to melt said opaque wall means, an opening communicating with said hollow interior, and thus said chamber, and the atmosphere. 28. (NEW) A member according to claim 27 and further including a membrane in said passage means normally blocking communication therethrough, wherein said conduit means includes a tubular cannula having a spiked end portion extending toward said membrane, and wherein said spiked end portion is brought into piercing contact with said membrane in response to said axial displacement of said housing means. 29. (NEW) A membrane according to claim 28 and further including frangible wall means in said conduit means for normally blocking flow communica¬ tion therethrough and means extending in said chamber and operatively connected with said frangible wall means for manually fracturing said frangible wall means in response to said transverse displacement of said housing means, thereby opening flow communicatio through said conduit means. 30. (NEW) An assembly according to claim 28 wherein said chamber includes an area of in¬ creased interior diameter radially spaced outwardly of said conduit means to expand the field of lateral movement of said conduit means within said chamber during said trans- verse movement of said housing means. 31. (NEW) An assembly for sealing a port communicating with the interior of the container and the atmosphere, said assembly comprising stopper means adapted for sealing engagement with the container port and including passage means communicat¬ ing with the container interior, connector means defining a fluid pathway having an end portion normally sealed from communication with the atmosphere, flexible mounting means carried by said stopper means and circumferentially defining a chamber extending outwardly of and in communication with said passage means, said flexible mounting means being operative for support¬ ing said connector means on said stopper means with said -23 normally sealed end portion disposed outwardly of said chamber and in communication with the.atmosphere and the remaining portion of said connector means disposed within said chamber and for further permitting, in response to 5 external forces, the resilient displacement of said con¬ nector means relative to said stopper means in directions axially and transversely of the longitudinal axis of said chamber, said chamber further including an area of 0 increased interior diameter radially spaced outwardly of said remaining portion of said connector means to expand the field of lateral movement of said remaining portion within said chamber during said transverse displacement of said connector means, and 5 means for opening said one normally sealed end of said connector means for communication with the atmosphere. 32. (NEW) An assembly according to claim 31 and further including a membrane in said passage 0 means normally blocking communication therethrough, wherein said remaining portion of said connector means includes a tubular cannula having a spiked end por¬ tion extending toward said membrane, and wherein said spiked end portion is brought into 5 piercing contact with said membrane in response to said axial disυlacement of said connector means. 33. (NEW) An assembly according to claim 31 and further including frangible wall means in said remaining portion of said connector means for normal- 0 ly blocking flow communication therethrough and means extending in said chamber toward said stopper means and operatively connected with said frangible wall means for manually fracturing said frangible wall means in response to said transverse displacement of said connector means, 5 thereby opening flow communication through said remaining OMPI IPO . portion of said connector means, O

Inventors: BELLAMY D, SMITH D
Applicants: BAXTER TRAVENOL LAB, BELLAMY D, SMITH D, BAXTER TRAVENOL LAB INC
Application year: 1980
Main classification: A61J1
IPC codes: A61J1, A61J3, A61M39