Patent Description:
Advances in medical treatment and improved procedures constantly increase the need for improved valves and connectors. The demands relating to variety of types, quality, needle safety, microbial ingress prevention and leak prevention are constantly growing. Additionally, advances in sampling or dose dispensing technologies, automated and manual, aseptic or non-aseptic applications, call for new safe concealing solutions for the sampling needle. One extremely demanding application exists in the field where medical and pharmacological personnel that are involved in the preparation and administration of hazardous drugs risk being exposed to hazardous drugs and to their vapors, which may escape to the surroundings. As referred to herein, a "hazardous drug" is any injectable material the contact with which, or with the vapors of which, may constitute a health hazard. Illustrative and non-limitative examples of such drugs include, inter alia, cytotoxins, antiviral drugs, chemotherapy drugs, antibiotics, and radiopharmaceuticals, such as herceptin, cisplatinum, fluorouracil, leucovorin, paclitaxel, etoposide, cyclophosphamideand neosar, or a combination thereof, in a liquid, solid, or gaseous state.

Hazardous drugs in liquid or powder form are contained within vials, and are typically prepared in a separate room by pharmacists provided with protective clothing, a mouth mask, and a laminar flow safety cabinet. A syringe provided with a cannula, i.e. a hollow needle, is used for transferring the drug from a vial. After being prepared, the hazardous drug is typically added to a solution contained in a bag which is intended for parenteral administration, such as a saline solution intended for intravenous administration.

Since hazardous drugs are toxic, direct bodily contact thereto, or exposure to even micro-quantities of the drug vapors, considerably increases the risk of developing medical conditions such as skin cancer, leukemia, liver damage, malformation, miscarriage and premature birth. Such exposure can take place when a drug containing receptacle, such as a vial, bottle, syringe, and intravenous bag, is subjected to overpressure, resulting in the leakage of fluid or air contaminated by the hazardous drug to the surroundings. Exposure to a hazardous drug also results from a drug solution remaining on a needle tip, on a vial or intravenous bag seal, or by the accidental puncturing of the skin by the needle tip. Additionally, through the same routes of exposure, microbial contaminants from the environment can be transferred into the drug and fluids; thus eliminating the sterility with possibly fatal consequences.

<CIT> and <CIT> to the inventor of the present invention describe closed system liquid transfer devices designed to provide contamination-free transfer of hazardous drugs. <FIG> and <FIG> are schematic cross-sectional views of the apparatus <NUM> for transferring hazardous drugs without contaminating the surroundings, according to one embodiment of the invention described in <CIT>. The main features of this apparatus that are relevant to the present invention will be described herein. Additional details can be found in the aforementioned patent.

The proximal section of apparatus <NUM> is a syringe <NUM>, which is adapted to draw or inject a desired volume of a hazardous drug from a fluid transfer component, e.g. a vial <NUM> or an intravenous (IV) bag in which it is contained and to subsequently transfer the drug to another fluid transfer component. At the distal end of syringe <NUM> is connected a connector section <NUM>, which is in turn connected to vial <NUM> by means of vial adaptor <NUM>.

Syringe <NUM> of apparatus <NUM> is comprised of a cylindrical body <NUM> having a tubular throat <NUM> that has a considerably smaller diameter than body <NUM>, an annular rubber gasket or stopper assembly <NUM> fitted on the proximal end of cylindrical body <NUM>, hollow piston rod <NUM> which sealingly passes through stopper <NUM>, and proximal piston rod cap <NUM> by which a user can push and pull piston rod <NUM> up and down through stopper <NUM>. A piston <NUM> made of an elastomeric material is securely attached to the distal end of piston rod <NUM>. Cylindrical body <NUM> is made of a rigid material, e.g. plastic.

Piston <NUM>, which sealingly engages the inner wall of, and is displaceable with respect to, cylindrical body <NUM> defines two chambers of variable volume: a distal liquid chamber <NUM> between the distal face of piston <NUM> and connector section <NUM> and a proximal air chamber <NUM> between the proximal face of piston <NUM> and stopper <NUM>.

Connector section <NUM> is connected to the throat <NUM> of syringe <NUM> by means of a collar which proximally protrudes from the top of connector section <NUM> and surrounds throat <NUM>. Note that embodiments of the apparatus do not necessarily have a throat <NUM>. In these embodiments syringe <NUM> and connector section <NUM> are formed together as a single element at the time of manufacture, or permanently attached together, e.g. by means of glue or welding, or formed with a coupling means, such as threaded engagement or a Luer connector. The connector section <NUM> comprises a double membrane seal actuator which is moveable in a reciprocating manner from a normal, first configuration in which the needles are concealed when the double membrane seal actuator is disposed in a first, distal position and a second position in which the needles are exposed when the double membrane seal actuator is proximally displaced. Connector section <NUM> is adapted to be releasably coupled to another fluid transfer component, which can be any fluid container with a standard connector such as a drug vial, intravenous bag, or an intravenous line to produce a "fluid transfer assembly", through which a fluid is transferred from one fluid transfer component to another.

Connector section <NUM> comprises a cylindrical, hollow outer body; a distal shoulder portion, which radially protrudes from the body and terminates at the distal end with an opening through which the proximal end of a fluid transfer component is inserted for coupling; a double membrane seal actuator <NUM>, which is reciprocally displaceable within the interior of the body; and one or more resilient arms <NUM> serving as locking elements, which are connected at a proximal end thereof to an intermediate portion of a cylindrical actuator casing that contains double membrane seal actuator <NUM>. Two hollow needles that function as air conduit <NUM> and liquid conduit <NUM> are fixedly retained in needle holder <NUM>, which protrudes into the interior of connector section <NUM> from a central portion of the top of connector section <NUM>.

Conduits <NUM> and <NUM> distally extend from needle holder <NUM>, piercing the upper membrane of actuator <NUM>. The distal ends of conduits <NUM> and <NUM> have sharp pointed ends and apertures through which air and liquid can pass into and out of the interiors of the conduits respectively as required during a fluid transfer operation. The proximal end of air conduit <NUM> extends within the interior of proximal air chamber <NUM> in syringe <NUM>. In the embodiment shown in <FIG>, air conduit <NUM> passes through piston <NUM> and extends inside of hollow piston rod <NUM>. Air flowing through conduit <NUM> enters/exits the interior of piston rod <NUM> and exits/enters to air chamber <NUM> through an aperture formed at the distal end of piston rod <NUM> just above piston <NUM>. The proximal end of liquid conduit <NUM> terminates at the top of or slightly proximally from the top of needle holder <NUM>, so that the liquid conduit will be in fluid communication with the distal liquid chamber <NUM> via the interior of throat <NUM> of syringe <NUM>.

Double membrane seal actuator <NUM> comprises a cylindrical casing that holds a proximal disc shaped membrane 34a having a rectangular cross-section and a two level distal membrane 34b having a T-shaped cross-section with disc shaped proximal portion and a disc shaped distal portion disposed radially inwards with respect to the proximal portion. The distal portion of the distal membrane 34b protrudes distally from actuator <NUM>. Two or more equal length resilient elongated arms <NUM> are attached to the distal end of the casing of actuator <NUM>. The arms terminate with distal enlarged elements. When actuator <NUM> is in a first position, the pointed ends of conduits <NUM> and <NUM> are retained between the proximal and distal membranes, isolating the ends of conduits <NUM> and <NUM> from the surroundings, thereby preventing contamination of the interior of syringe <NUM> and leakage of a harmful drug contained within its interior to the surroundings.

Vial adaptor <NUM> is an intermediate connection that is used to connect connector section <NUM> to a drug vial <NUM> or any other component having a suitably shaped and dimensioned port. Vial adaptor <NUM> comprises a disk shaped central piece to which a plurality of circumferential segments, formed with a convex lip on the inner face thereof for facilitating securement to a head portion of a vial <NUM>, are attached at the circumference of the disk and pointing distally away from it and a longitudinal extension projecting proximally from the other side of the disk shaped central piece. Longitudinal extension fits into the opening at the distal end of connector section <NUM> to allow transfer of the drug as described herein below. The longitudinal extension terminates proximally with a membrane enclosure having a diameter larger than that of the extension. A central opening in the membrane enclosure retains and makes accessible a membrane 15a.

Two longitudinal channels, which are internally formed within the longitudinal extension and that extend distally from the membrane in the membrane enclosure, are adapted to receive conduits <NUM> and <NUM>, respectively. A mechanical guidance mechanism is provided to insure that the conduits <NUM> and <NUM> will always enter their designated channel within the longitudinal extension when connector section <NUM> is mated with vial adaptor <NUM>. The longitudinal extension terminates distally with a spike element 15b which protrudes distally. The spike element is formed with openings in communication with the internally formed channels, respectively and openings at its distal pointed end.

Vial <NUM> has an enlarged circular head portion attached to the main body of the vial with a neck portion. In the center of the head portion is a proximal seal 16a, which is adapted to prevent the outward leakage of a drug contained therein. When the head portion of vial <NUM> is inserted into the collar portion of vial adaptor <NUM> and a distal force is applied to vial adaptor <NUM>, the spike element 15b of the connector section <NUM> pierces the seal 16a of vial <NUM>, to allow the internal channels in the connector section <NUM> to communicate with the interior of drug vial <NUM>. When this occurs, the circumferential segments at the distal end of the collar portion of the connector section are securely engaged with the head portion of vial <NUM>. After the seal of vial <NUM> is pierced it seals around the spike preventing the outward leakage of the drug from the vial. At the same time the tops of the internal channels in vial adaptor <NUM> are sealed by the membrane 15a at the top of vial adaptor <NUM>, preventing air or drug from entering or exiting the interior of vial <NUM>.

The procedure for assembling drug transfer apparatus <NUM> is carried out as shown in <FIG>: Step <NUM> - After the vial <NUM> and vial adaptor <NUM> have been joined together, with spike element 15b penetrating proximal seal 16a of the vial, the membrane enclosure 15a of vial adaptor <NUM> is positioned close to the distal opening of connector section <NUM>, as shown in <FIG>. Step <NUM> - A double membrane engagement procedure is initiated by distally displacing the body of connector section <NUM> with an axial motion until the membrane enclosure and longitudinal extension of vial adaptor <NUM> enters the opening at the distal end of the connector section <NUM>, as shown in <FIG>. Step <NUM> - the distal membrane 34b of actuator <NUM> is caused to contact and be pressed against the stationary membrane 15a of vial adaptor <NUM> by additional distal displacement of the body of the connector section <NUM>. After the membranes are pressed tightly together the enlarged elements at the ends of the arms of the connector section <NUM> are squeezed into the more narrow proximal section of connector section <NUM> thereby holding the membranes pressed together and engaged around the longitudinal extension and under the membrane enclosure of vial adaptor <NUM>, as shown in <FIG>, thereby preventing disengagement of the double membrane seal actuator <NUM> from vial adaptor <NUM>. Step <NUM> - Additional distal displacement of the body of connector section <NUM>, as shown in <FIG>, causes actuator <NUM> to move proximally relative to the body of the connector section <NUM> until the tips of conduits <NUM> and <NUM> pierce the distal membrane of actuator <NUM> and the membrane at the top of vial adaptor <NUM> and are in fluid communication with the interior of vial <NUM>. These four steps are performed by one continuous axial motion as connector section <NUM> is distally displaced relative to the vial adaptor <NUM>, and they will be reversed to separate connector section <NUM> from vial adaptor <NUM> by pulling connector section <NUM> and vial adaptor <NUM> apart. It is important to emphasize that the procedure is described herein as comprising four separate steps, however this is for ease in describing the procedure only. It is to be realized that in actual practice the secured double membrane engagement (and disengagement) procedure using the present invention is carried out using a single smooth axial movement.

After drug transfer assembly <NUM> shown in <FIG> is assembled as described hereinabove with reference to <FIG>, the piston rod <NUM> can be moved to withdraw liquid from vial <NUM> or to inject liquid from the syringe into the vial. The transfer of liquid between the distal liquid chamber <NUM> in the syringe <NUM> and liquid <NUM> in the vial <NUM> and transfer of air between the proximal air chamber <NUM> in the syringe <NUM> and air <NUM> in the vial <NUM> takes place by an internal pressure equalization process in which the same volumes of air and liquid are exchanged by moving through separate channels symbolically shown in <FIG> by paths <NUM> and <NUM> respectively. This is a closed system which eliminates the possibility of exchange of air or liquid drops or vapor between the interior of assembly <NUM> and the surroundings.

<FIG> schematically shows injection of a liquid into a vial. To inject liquid contained in the liquid chamber <NUM> of syringe <NUM> into the vial <NUM> the drug transfer assembly <NUM> must be held vertically with the vial at the bottom in an upright position as shown in <FIG>. Pushing piston <NUM> distally pushes the liquid out of liquid chamber <NUM> through conduit <NUM> into vial <NUM>. Simultaneously, as the volume of liquid chamber <NUM> is reduced by the distally moving piston, the volume of air chamber <NUM> is increased. This creates a temporary state of negative pressure in the air chamber and therefore air (or an inert gas) inside vial <NUM> will be sucked through conduit <NUM> into air chamber <NUM>. Additionally and simultaneously, as the liquid is added to the vial, the volume available for the air in the vial is reduced creating a temporary state of positive pressure, therefore the air is forced from the vial <NUM> through conduit <NUM> into air chamber <NUM>, thus equalizing the pressures in the transfer assembly <NUM> and equilibrium is reached when piston <NUM> stops moving.

<FIG> schematically shows withdrawal of liquid from a vial. To withdraw liquid from the vial <NUM> and transfer it into the liquid chamber <NUM> of syringe <NUM> the drug transfer assembly <NUM> must be inverted and held vertically with the vial <NUM> in an upside-down position as shown <FIG>. For this operation, when apparatus <NUM> is assembled and the piston <NUM> in syringe <NUM> is pulled in the proximal direction, a state of negative pressure is created in liquid chamber <NUM> and liquid is sucked into it through conduit <NUM>. Simultaneously the volume of air chamber <NUM> is reduced and air is forced out of it through conduit <NUM> into the vial (in <FIG> are shown the air bubbles created by the air entering the vial from air chamber <NUM>). As described in <FIG> this simultaneous transfer and replacing of equal volumes of gas and liquids respectively inside syringe and vial constitutes the closed system equalization system.

Despite the care that was taken to separate air path <NUM> from liquid path <NUM> there are two locations in the prior art assembly described in <CIT> in which these paths intersect under certain conditions allowing for the possibility of liquid to travel through the air conduit from the distal liquid chamber <NUM> or vial <NUM> to the proximal air chamber.

Specifically, in the prior art apparatus described in <CIT> there is a direct connection between the air and liquid channels:.

When part of the liquid does accidently find its way into the air chamber of the syringe, in addition to the obvious problems of esthetics, additional time consuming working steps become necessary to retrieve the drug and correct the dosage.

An example of a scenario when situation A is relevant is when the syringe contains liquid and is being handled, for example when being transported from the pharmacy to the ward. At such a time the piston rod might be accidentally pushed causing some of the drug to migrate to the proximal air chamber above the piston from where it cannot be expelled from the syringe. In such case the plunger needs to be pulled back in order to retrieve the drug, which is an extra work step and the wet residuals in the air chamber <NUM> cause an aesthetic problem.

An example of a scenario when situation B is relevant is when, during withdrawal of a liquid drug from a vial which is in a typical upside-down position, a bubble of air is seen to enter the liquid chamber of the syringe or when the syringe has been filled with more than the desired volume of liquid. In these situations, accidental pushing on the piston rod to return liquid or bubble to the vial will also cause some liquid to be forced through the air channel into the air chamber in the syringe. The way to remove the bubble is a relatively time consuming and complex procedure involving disconnecting the syringe from the vial and reconnecting it. Special attention is required to avoid pushing the plunger accidentally, which slows down the speed of work.

<CIT> to the inventor of the present invention describes improvements to the previously described drug transfer devices that minimize or eliminate the above mentioned limitations. Amongst the improvements taught in <CIT> are embodiments of the drug transfer apparatus that comprises a hydrophobic filter inserted in the air channel in at least one location between the air chamber in the syringe and the fluid transfer component and improved vial adaptors.

The inserted filter in the vial adaptor serves as barrier between the liquid and air channels, thus preventing the transfer of liquid through the air channels to the air chamber formed at the back of the syringe. Due to insertion of such barrier the user is free to push small air bubbles or correct small over dosage back into the vial during withdrawal procedure without being concerned that the drug might migrate to the air chamber. On one hand working with filter barrier seems to be an advantage but on the other hand the user is motivated to some negligence and it can be expected that users will not clear the filter from liquid before disconnecting the syringe from the vial and some pressure differentials might remain between the air and liquid chambers of the syringe. Therefore right after disconnection the pressure differentials will seek for neutralization and flow of fluids will occur from the chamber with the higher pressure to chamber with the lower pressure until equilibrium is reached. In case the lower pressure is in the air chamber, this will suck some of the liquid drug from the liquid chamber to the air chamber through the path existing between both needle tips inside the double membrane seal actuator. To avoid such migration or transfer due to accidental pushing or pulling the plunger and generally to prevent any uncontrolled migration of liquid to air the chamber, the existing path between the needle tips must be eliminated and total isolation of the needles is required.

Such isolation of the needles constitutes a design challenge. On the one hand, membrane 34b serves as a barrier between the open ends of the needles <NUM> and <NUM> and the environment, preventing contaminants such as microorganisms from contaminating the interior of actuator <NUM> and the needle tips retained in it, thereby maintaining sterility. On the other hand membrane 34b also protects the environment from hazardous substances. While in the previous embodiment in <FIG> where no filter barrier is used, there is no pressure differential created between the air and liquid chambers, and therefore uncontrolled migration doesn't occur, only accidental pushing or pulling can cause transfer of drug between chambers. Such accidental pushing, which (as a side note) is very common, does not create high pressure inside the double membrane seal actuator since there is free flow from chamber to chamber and high pressure cannot be maintained and collapses immediately until equilibrium is reached. Therefore the sealing properties of the elements in the actuator are never challenged with high pressure and moderate design is sufficient. On the other hand, in embodiments according to <CIT> (see for example <FIG> herein below) where a filter <NUM> is inserted as a barrier, there is a requirement for high pressure resistance due to the high pressures of up to <NUM> atmospheres that can be easily generated by manually pushing the syringe plunger. This phenomenon is especially common with small volume syringes (<NUM>-<NUM>). Under such pressures most of the isolation designs between the needles will fail and drug will be transferred to the air chamber or even worse, the membranes 34a and 34b cannot resist high pressures, which can cause them to detach from their seat or can cause a leak through the channels in the membranes that were created by the needles during piercing the resilient material of the membrane.

<CIT> and <CIT>, both to the inventor of the present invention, describe needle valves that can be incorporated into the membrane actuator of the connector section <NUM>. The needle valves prevent the possibility of liquid travel through the air conduit from the distal liquid chamber <NUM> or vial <NUM> to the proximal air chamber when the connector section <NUM> is not connected to a vial or other fluid transfer component. The needle valves also simplify the construction of the membrane actuator making it possible to use a single membrane actuator instead of a double membrane actuator as in the connector section shown in <FIG>.

<FIG> and <FIG> are schematic cross-sectional views of an apparatus for transferring hazardous drugs. The apparatus and all of the components shown in these figures are identical to those shown in <FIG> and <FIG> respectively, with two exceptions. The vial adaptor <NUM> comprises a filter <NUM>, as described in <CIT> and the prior art double membrane seal actuator <NUM> in the connector section <NUM>, which comprises two membranes 34a and 34b and arms <NUM>, is replaced with an actuator <NUM> comprising an embodiment of a needle valve, only one membrane 34b, and arms <NUM>. It is important to note that it is not necessary to seal the proximal end of actuator <NUM> in any fashion because the task of enclosing the ports <NUM> at the distal ends of the air and liquid conduits when the connector is not connected to another fluid transfer component, which in the prior art was accomplished by membranes 34a and 34b, is accomplished in the single membrane actuator by the needle valve arrangement and membrane 34b alone and in some embodiments by the needle valve itself.

<FIG> shows syringe <NUM> attached to connector section <NUM> and vial adaptor <NUM> connected to drug vial <NUM>. <FIG> shows all components of the apparatus connected together. <FIG> and <FIG> are enlarged views of the actuator in the apparatus shown in <FIG> and <FIG> respectively.

Referring to <FIG> and <FIG>, actuator <NUM> comprises a valve seat <NUM> comprising two bores through which the needles of air conduit <NUM> and liquid conduit <NUM> pass. It is noted that embodiments of actuator <NUM> are also described that contain one bore for use in liquid transfer apparatus that comprises only one needle <NUM>.

When the syringe and attached connector are not connected to any other component of the apparatus, as shown in <FIG>, the actuator <NUM> is at the distal end of connector section <NUM> and the tips of needles <NUM> and <NUM> are located in the bores in the seat <NUM> of the needle valve. In this configuration the ports <NUM> in the sides of the needles are blocked by the interior walls of the bores completely isolating the needles from each other, thereby preventing air from entering the liquid chamber of the syringe or liquid from entering the air chamber.

When the syringe and attached connector are connected to another component of the apparatus, such as a vial adaptor as shown in <FIG>, the actuator <NUM> is pushed towards the proximal end of connector section <NUM>. Since needles <NUM> and <NUM> are fixed to the needle holder <NUM>, as actuator <NUM> moves proximally, the tips of needles <NUM> and <NUM> and ports <NUM> are pushed out through the distal end of the bores in the seat <NUM> of the needle valve, through membrane 34b, and through membrane 15a of the vial adaptor, thereby establishing open fluid paths in the respective channels.

The first goal for the connector is to completely eliminate the possibility of migration of liquid to the air chamber. This can happen, for example, if pressure differentials between the air and liquid chambers exist after disconnection from a vial adaptor and if the pressure in the air chamber is lower than that in the liquid chamber, resulting in undesired migration of liquid to the air chamber. The second goal is to prevent leaks or damage to the connector during accidental pushing of the syringe plunger. One of the frequently performed drug transfer operations in hospital settings is known as IV push or bolus injection. Typically the required amount of drug is prepared in a syringe in the hospital pharmacy and delivered to the ward where a qualified nurse administers the drug to the patient through a previously established IV line. A common problem associated with the procedure is that during the trip from pharmacy to ward or at bedside the piston of the syringe is sometimes unintentionally pushed expelling some of the drug from the barrel of the syringe or the piston is unintentionally pulled. High pressures of up to <NUM> atmospheres can be easily generated by manually pushing the plunger of small volume syringes (<NUM>-<NUM>). Such pressure may cause the connector to disintegrate or the membranes to be detached. The connector shown in <FIG> is proposed as a solution to the problems associated with such unintended transfer of fluids between the air and liquid chambers and to resist high pressures created during accidental pushing the of plunger. As can be seen in these figures, when the connector <NUM> is not connected to the adapter <NUM>, the ports <NUM> at the distal end of needles <NUM> and <NUM> that allow exchange of fluid between the surroundings and the hollow interiors of the needles are blocked by the interior of the bore in seat <NUM> of the needle valve. If the syringe is filled or partially filled with liquid, then if a force is exerted to try to push the plunger forward and to force liquid to flow through the needle, no liquid can exit the needle through port <NUM>. Conversely, if a force is exerted to pull the plunger backwards no air can enter through port <NUM> and flow through the interior of the needle into the barrel of the syringe.

The actuators <NUM> described in <CIT> and <CIT> are identical except for the material of which seat <NUM> is manufactured. In <CIT> seat <NUM> is made of a rigid material such as a rigid low friction plastic, e.g. acetal. The bores in seat <NUM> have diameters very close to the outer diameters of needles <NUM> and <NUM> so that the needles slidingly fit into the bores in the seat while preventing passage of liquid or air molecules into or out of the interior of the needles when the tips of the needles are in the bores. The diameters of the shaft and the bores require fine tuning during the product development phase, since a tighter bore causes higher friction and higher pressure resistance, while a less tight bores causes less friction and moderate pressure resistance. The surface quality of the needles as well as the lubricant applied during the manufacture process influences the amount of friction. Materials such as acetal have excellent low friction properties and allow the valve to function even after the lubricant has been removed due to repeated connections and exposure to aggressive substances in the drugs.

In <CIT> seat <NUM> is made of a resilient material such as PVC. The bores in seat <NUM> have diameters slightly smaller than the outer diameters of needles <NUM> and <NUM> so that when the needles are pushed into the bores the resilient material of the bore pushes radially against the outer surface of the needle sealing the ports <NUM> preventing passage of liquid or air molecules into or out of the interior of the needles. Each specific system may use a different tolerance in the difference between the diameters of the needles and the bores, balancing between the maximal force allowed to move the needle so as to maintain user's convenience, and the pressure resistance desired of the valve to prevent leaks, so as to maintain safety. The entire seat may be made of resilient material or seat <NUM> may be made of a rigid material with a sleeve made of resilient material that fits into a channel of larger diameter provided in the seat.

The advantages and disadvantages of the two types of seat complement each other. On the one hand, the seat made of rigid material is very resistant to leaking at high pressures but it is difficult and expensive to manufacture to the high tolerances required. On the other hand, the seat made of resilient material is relatively easy and inexpensive to manufacture but is prone to potential leakage at high pressures.

It is a purpose of the present invention to provide septum actuators of different designs that employ the previously developed needle valves in novel configurations.

Further purposes and advantages of this invention will appear as the description proceeds.

In a first aspect the invention is a septum holder comprising: a disk shaped annular body having a cylindrical bottom part that projects downward, a cavity created in the bottom part of the body, an insert comprising at least one bore that forms the seat of a needle valve fitted into the cavity, at least one resilient elongated arm attached to the side of the body, the at least one arm projecting downward and terminating with a distal enlarged element, and a septum;
wherein the septum is made of a single piece of cylindrically shaped resilient material, the upper part of the septum has a hollow interior forming a cylindrical recess having an inner diameter no larger than that of the outer diameter of the cylindrical section at the bottom of the body of the septum holder, the lowest part of the septum has a diameter that matches that of a septum in a fluid transfer component, and the septum is adapted to be pushed over the bottom part of the body of the septum holder until the solid part of the septum below the recess butts against the bottom of the at least one bore in the insert.

In embodiments of the septum holder the septum is fixedly held on the body of the septum holder in one of the following ways: the resilient material of the septum may be strong enough to grip the sides of the cylindrical section at the bottom of the septum holder body to hold the septum in place; the cylindrical section at the bottom of the septum holder body may have threads or teeth, or an equivalent structure created on its outer surface and the septum may have a similar structure on the inner diameter of its hollow interior so that the two structures interlock when the septum is pushed over the bottom part of body; by gluing; by ultrasound forming; and by laser or ultrasound welding.

In embodiments of the septum holder the insert is made of one of: a resilient material and a rigid material.

In a second aspect the invention is a syringe connector section for a liquid transfer apparatus, the syringe connector section comprising: a cylindrical body adapted to be attached to a syringe, the body having a shoulder portion at its distal end; at least one hollow needle fixedly attached to the upper end of the body of the connector section, the needle having at least one port that allows fluid communication between the exterior and the hollow interior of the needle at the lower end of the needle adjacent to its pointed distal tip;.

In embodiments of the syringe connector section, when not connected to another element of the liquid transfer system, the sides of the at least one bore in the insert in the body of the septum holder push against the shaft of the at least one needle sealing the port at the lower end of the needle preventing fluids from entering or exiting the interior of the needle and the tip of the at least one needle is isolated from the outside by the septum of the septum holder.

In embodiments of the syringe connector section the liquid transfer apparatus is a closed system, the syringe connector section comprises two needles, and the insert in the body of the septum holder comprises two bores functioning as the seats of needle valves.

All the above and other characteristics and advantages of the invention will be further understood through the following illustrative and non-limitative description of embodiments thereof, with reference to the appended drawings.

The present invention is an embodiment of septum holder for use in syringe connectors that are used to connect syringes to other elements of liquid transfer apparatuses. Other embodiments of the septum holders described herein comprise a septum holder body, at least one resilient elongated arm that terminates with a distal enlarged element attached to the sides of the body, and a septum. The septum holder of the invention is characterized in that it comprises at least one bore that functions as the seat of a needle valve. The bore is created in the septum or in an insert fixed in either the body of the septum holder or in the septum. The septum holder of the invention is also characterized in that the septum is attached to the bottom of the body of the septum holder projecting downwards parallel to the at least one elongated arm.

The embodiments of the septum holder that are described herein below all have two bores for use in syringe connectors that comprise two hollow needles, they also have two resilient arms attached to the body part. However it is to be understood that these same embodiments can be manufactured mutatis mutandis with only one bore to be used with syringe connectors that comprise one hollow needle and one, three, or more arms. Also it is apparent that in embodiments where the two arms are shown attached to the sides of the body at a certain location, it would require only a simple modification to attach them at other locations.

<FIG>, and <FIG> are respectively front, cross-sectional, and exploded views of a first embodiment of a septum holder <NUM>. Septum holder <NUM> is comprised of a body <NUM> having a disk shaped annular upper body part 702a and a lower body part 702b. Two equal length resilient elongated arms <NUM> are attached to the sides of body <NUM>. The arms terminate with distal enlarged elements <NUM>.

As can be seen in exploded view of <FIG>, a septum <NUM> is fitted into the lower body part 702b so that it extends downward between arms <NUM>. Septum <NUM> is made of a single piece of cylindrically shaped resilient material. The upper part of septum <NUM> has a diameter larger than the middle part in order to form a flange that rests on an annular ledge 702c created around the inside of the bottom section 702b of body <NUM> when the middle part of septum <NUM> slides through the open center at the bottom of bottom section 702b. Upper section 702a is then pushed onto the lower section in order to connect septum <NUM> to body <NUM>. The upper and lower sections of body <NUM> can be held permanently together with the septum <NUM> held between them by any method known in the art, e.g. press fitting, gluing, snap fitting, ultrasonic forming, and laser or ultrasonic welding.

In an alternative embodiment the septum, shaped as described above can be forced into the circular opening at the bottom of the bottom section 702b from below and, when the flange snaps onto annular ledge 702c the upper section 702a of the body is pushed into the lower section 702b to hold the septum in place. In another embodiment, the upper and middle sections of the septum can have the same diameter that is at least as large as the diameter of annular ledge 702c. In this embodiment the septum is forced into the lower section 702b from the bottom. Because of the flexibility of the material of which the septum is made the upper part of the septum is at first compressed to enter the lower section of the holder and then expands to fill the space on top of ledge 702c.

Two bores <NUM> that function as the seat of a needle valve are created part of the way through the height of the middle part of septum <NUM>. The lowest part of septum <NUM> has a diameter that matches that of the septum in the fluid transfer component, e.g. vial adaptor, to which it will be connected. Note that in <FIG> the lower part of the septum is shown as having a diameter less than that of the rest of the septum; however, this is not always necessary and in some cases the lower part of the septum can have the same diameter as the middle part of the septum or the entire septum can have the same diameter. The only condition being that the septum in the septum holder has to be able to contact a septum in a fluid transfer component and form a seal that prevents leakage of air or liquid.

<FIG> schematically shows the holder of <FIG>, and <FIG> in a syringe connector section of a closed system liquid transfer apparatus. The connector section is essentially the same as that in the prior art apparatus described herein above. Cylindrical body <NUM> of the connector section is attached to syringe <NUM>. Two hollow needles <NUM>, which function as an air conduit, and <NUM>, which functions as a liquid conduit, are fixedly attached to the upper end of body <NUM> of the connector section. At the lower end of the needles, adjacent to the pointed distal tips, are ports <NUM> that allow fluid communication between the exterior and the hollow interiors of the needles. External ridges <NUM> near the bottom of cylindrical body <NUM> serve as finger grips for use when attaching the connector section and syringe to other elements of the drug transfer system. Ridges <NUM> are not essential and can be eliminated or replaced with other means, for example a roughened surface area, to accomplish the same purpose.

A septum holder <NUM> is located inside of cylindrical body <NUM> of the connector section. As shown, the distal ends of needles <NUM>,<NUM> are inserted into bores <NUM> in septum <NUM>. The diameters of bores <NUM> are smaller than the outer diameter of the shafts of the needles and therefore the resilient material of which the septum is manufactured pushes radially against the shaft of the needle sealing the ports <NUM>. When not connected to another element of the liquid transfer system the distal enlarged elements <NUM> of arms <NUM> are engaged in the shoulder portion <NUM> at the distal end of body <NUM>. As shown in <FIG>, in this position the tips of the needles are isolated from the outside by septum <NUM> and the walls of the bores <NUM> pressing radially inwards on the shafts of the needles prevent fluids from entering or exiting the interior of the needles.

Connection of the syringe connector to a fluid transfer component, e.g. a vial adaptor, a spike adaptor for connection to an IV bag, or a connector for connection to an IV line, is accomplished in the same manner as in the prior art described herein above. When the septum of the fluid transfer component is pushed against septum <NUM>, septum holder <NUM> begins to move upwards inside body <NUM> and the tips of the needles begin to exit bores <NUM> penetrate the solid material of septum <NUM>. The tips of the needles pass through septum <NUM> and the septum of the fluid transfer component as holder <NUM> continues to be pushed upwards, thereby establishing air and liquid channels between the element of the liquid transfer system attached to the fluid transfer component and the proximal air chamber and distal liquid chamber in the syringe.

<FIG>, and <FIG> are respectively front, cross-sectional, and exploded views of a second embodiment of a septum holder <NUM>. Septum holder <NUM> is comprised of a body <NUM> having a disk shaped annular upper body part 702a and a lower body part 702b. Two equal length resilient elongated arms <NUM> are attached to the sides of lower body part 702b. The arms terminate with distal enlarged elements <NUM>.

In an alternative embodiment the septum <NUM>, shaped as described above can be forced into the circular opening at the bottom of the bottom section 702b from below and, when the flange snaps onto annular ledge 702c the upper section 702a of the body is pushed into the lower section 702b to hold the septum in place. In another embodiment, the upper and middle sections of the septum can have the same diameter that is at least as large as the diameter of annular ledge 702c. In this embodiment the septum is forced into the lower section 702b from the bottom. Because of the flexibility of the material of which the septum is made the upper part of the septum is at first compressed to enter the lower section of the holder and then expands to fill the space on top of ledge 702c.

A cavity <NUM> is created in the middle part of septum <NUM> is created into which an insert <NUM> is fitted. Insert <NUM> can be a single piece of material comprising two bores <NUM> that function as the seat of a needle valve as shown in <FIG>. In alternative embodiments insert <NUM> can have different shapes than that shown and in one embodiment can be comprised of two separate pieces of tubing that are inserted into parallel bores of appropriate diameters created into the middle part of septum <NUM>. The lowest part of septum <NUM> has a diameter that matches that of the septum in the fluid transfer component, e.g. vial adaptor, to which it will be connected. This embodiment of the septum is very useful because the required elasticity properties of the septum and of the insert <NUM> are different. The septum itself should be very elastic with good re-sealing properties while the material of the insert must be less flexible to resist pressures on the needle ports. For example, septum <NUM> can be made from Polyisoprene and insert <NUM> from silicon.

<FIG> schematically shows the holder of <FIG>, and <FIG> in a syringe connector section of a closed system liquid transfer apparatus. The connector section is essentially the same as that in the prior art apparatus described herein above. Cylindrical body <NUM> of the connector section is attached to syringe <NUM>. Two hollow needles <NUM>, which function as an air conduit, and <NUM>, which functions as a liquid conduit, are fixedly attached to the upper end of body <NUM> of the connector section. At the lower end of the needles, adjacent to the pointed distal tips, are ports <NUM> that allow fluid communication between the exterior and the hollow interiors of the needles. External ridges <NUM> near the bottom of cylindrical body <NUM> serve as finger grips for use when attaching the connector section and syringe to other elements of the liquid transfer system. Ridges <NUM> are not essential and can be eliminated or replaced with other means, for example a roughened surface area, to accomplish the same purpose.

A septum holder <NUM> is located inside of cylindrical body <NUM> of the connector section. As shown, the distal ends of needles <NUM>,<NUM> are inserted into bores <NUM> in insert <NUM> in septum <NUM>. If insert <NUM> is made of resilient material, the diameters of bores <NUM> are smaller than the outer diameter of the shafts of the needles and therefore the resilient material of which the insert is manufactured pushes radially against the shaft of the needle sealing the ports <NUM>. In embodiments of septum holder <NUM> the insert <NUM> can be made of a rigid material, e.g. acetal plastic. In these embodiments the diameters of the bores <NUM> are very close to the outer diameters of the needles and sealing of ports <NUM> is the result of the close manufacturing tolerances. When not connected to another element of the liquid transfer system the distal enlarged elements <NUM> of arms <NUM> are engaged in the shoulder portion <NUM> at the distal end of body <NUM>. As shown in <FIG>, in this position the tips of the needles are isolated from the outside by septum <NUM> and the walls of the bores <NUM> pressing radially on the shafts of the needles prevent fluids from entering or exiting the interior of the needles.

<FIG>, and <FIG> are respectively front, cross-sectional, and exploded views of a third embodiment of a septum holder <NUM> according to the invention. Septum holder <NUM> is comprised of a disk shaped annular body <NUM>. Two equal length resilient elongated arms <NUM> are attached to the sides of body <NUM>. The arms terminate with distal enlarged elements <NUM>. The bottom part of body <NUM> is comprised of a cylindrical section that projects downward between arms <NUM>. A cavity <NUM> is created in the bottom part of body <NUM> into which is fitted an insert <NUM> comprising two bores <NUM> that form the seat of a needle valve. In alternative embodiments insert <NUM> can have different shapes than that shown and in one embodiment can be comprised of two separate pieces of tubing that are inserted into parallel bores of appropriate diameters created in the bottom part of body <NUM>.

Septum <NUM> is made of a single piece of cylindrically shaped resilient material. The upper part of septum <NUM> has a hollow interior forming a cylindrical recess <NUM> having an inner diameter no larger than that of the outer diameter of the cylindrical section at the bottom of body <NUM>. After insert <NUM> is fitted into cavity <NUM>, septum <NUM> is pushed over the bottom part of body <NUM> until the solid part of septum <NUM> below recess <NUM> butts against the bottom of bores <NUM> in insert <NUM> thereby isolating bottoms of the interior of the bores from the external environment. Septum <NUM> is fixedly held on the body <NUM> of holder <NUM> by any means known in the art. For example, the resilient material of the septum may be strong enough to grip the sides of the cylindrical section at the bottom of body <NUM> to hold the septum in place; or, as shown in <FIG>, the cylindrical section at the bottom of body <NUM> may have threads or teeth, or an equivalent structure created on its outer surface and septum <NUM> may have similar structure on the inner diameter of its hollow interior (not shown in <FIG>) so that the two structures interlock when septum <NUM> is pushed over the bottom part of body <NUM>. In other embodiments other methods, such as gluing, ultrasonic forming, or laser or ultrasound welding may be used. The lowest part of septum <NUM> has a diameter that matches that of the septum in the fluid transfer component, e.g. vial adaptor, to which it will be connected.

A septum holder <NUM> is located inside of cylindrical body <NUM> of the connector section. As shown, the distal ends of needles <NUM>,<NUM> are inserted into bores <NUM> in insert <NUM>. If the insert <NUM> is made of a flexible material, e.g. silicon, the diameters of bores <NUM> are smaller than the outer diameter of the shafts of the needles and therefore the resilient material of which the insert is manufactured pushes radially against the shaft of the needle sealing the ports <NUM>. When not connected to another element of a liquid transfer system the distal enlarged elements <NUM> of arms <NUM> are engaged in the shoulder portion <NUM> at the distal end of body <NUM>. As shown in <FIG>, in this position the tips of the needles are isolated from the outside by septum <NUM> at the bottom and the walls of the bores <NUM> pressing radially on the shafts of the needles prevent fluids from entering or exiting the interior of the needles.

<FIG>, and <FIG> are respectively front, cross-sectional, and exploded views of a fourth embodiment of a septum holder <NUM>. Septum holder <NUM> comprises body <NUM> having a disk shaped annular lower body portion 1002b and an H-shaped upper body portion 1002a. Two equal length resilient elongated arms <NUM> are attached to the sides of the vertical posts of the upper body portion 1002a. The arms terminate with distal enlarged elements <NUM>. A septum <NUM> is attached to the bottom of body <NUM> extending downward from body <NUM> between arms <NUM>.

The horizontal bar in the upper body section 1002a and the bottom section 1002b of holder body <NUM> are configured to fixedly support an insert <NUM> comprising two bores <NUM> that form the seat of a needle valve. In alternative embodiments insert <NUM> can have different shapes than that shown and in one embodiment can be comprised of two separate parallel pieces of tubing.

In alternative embodiments, instead of an H-shaped upper body portion 1002a, the upper body portion of the septum holder can comprise more than two vertical posts and more than one horizontal bar. The requirement being that the arrangement of vertical posts and horizontal bars is configured to fixedly support the upper end of insert <NUM> and that, in this embodiment the insert <NUM> stands exposed to the environment and is not enclosed in the septum or septum holder body like in the previous embodiments.

Septum <NUM> is made of a single piece of cylindrically shaped resilient material. The upper part of septum <NUM> fits into a seat <NUM> created around the inside of the bottom portion 1002b of body <NUM>. Septum <NUM> is held fixedly in seat <NUM> by any method known in the art, e.g. press fitting, gluing, snap fitting, ultrasonic forming, and laser or ultrasonic welding. The lower part of septum <NUM> has a diameter that matches that of the septum in the fluid transfer component, e.g. vial adaptor, to which it will be connected.

<FIG> schematically shows the holder of <FIG>, and <FIG> in a syringe connector section of a closed system liquid transfer apparatus. The connector section is essentially the same as that in the prior art apparatus described herein above. Cylindrical body <NUM> of the connector section is attached to syringe <NUM>. Two hollow needles - <NUM>, which functions as an air conduit, and <NUM>, which functions as a liquid conduit, are fixedly attached to the upper end of body <NUM> of the connector section. At the lower end of the needles, adjacent to the pointed distal tips, are ports <NUM> that allow fluid communication between the exterior and the hollow interiors of the needles. External ridges <NUM> near the bottom of cylindrical body <NUM> serve as finger grips for use when attaching the connector section and syringe to other elements of the drug transfer system. Ridges <NUM> are not essential and can be eliminated or replaced with other means, for example a roughened surface area, to accomplish the same purpose.

Claim 1:
A septum holder (<NUM>) comprising: a disk shaped annular body having a cylindrical bottom part that projects downward, a cavity (<NUM>) created in the bottom part of the body, an insert (<NUM>) comprising at least one bore (<NUM>) that forms a seat of a needle valve fitted into the cavity (<NUM>), at least one resilient elongated arm (<NUM>) attached to a side of the body, the at least one arm (<NUM>) projecting downward and terminating with a distal enlarged element (<NUM>), and a septum (<NUM>);
the septum (<NUM>) being made of a single piece of cylindrically shaped resilient material, wherein an upper part of the septum (<NUM>) has a hollow interior forming a cylindrical recess (<NUM>) having an inner diameter no larger than that of an outer diameter of the cylindrical bottom part of the body of the septum holder (<NUM>), a lowest part of the septum (<NUM>) has a diameter that matches that of a septum in a fluid transfer component, and the septum (<NUM>) is adapted to be pushed over the bottom part of the body of the septum holder (<NUM>) until a solid part of the septum (<NUM>) below the recess butts against a bottom of the at least one bore (<NUM>) in the insert (<NUM>).