Drug handling apparatus and method.

0001This invention relates to a substance handling apparatus and method, and, more particularly, relates to a drug handling apparatus and method.

0002It is well known that various substances can, or must, be packaged for use at a later time and/or place. This is particularly true, for example, with respect to drugs, and various attempts have been heretofore made to package drugs with a view toward overcoming the many problems associated therewith.

0003Heretofore, it has been quite common, for example, in pre­filled drug packaging, to provide unit doses wherein the entire contens of the prepared package are delivered to the patient with no attempt being made to individualize the dosage.

0004Known devices and methods for providing an/or utilizing pre-filled drug packages, however, have heretofore required significant manual labor, particularly, in administering the contents, even though preparation time was often reduced relative to non-pre­filled packages, and most known packaging for injectable drugs has not been designed for integration with delivery control devices that allow multiple doses to be administered to a patient.

0005Traditional multi-dose containers have, typically, been intended for reconstitution with diluent and dispensing from separate containers, each of which has to be filled with the drug solution. Normally these containers have been simple bottles using a needle penetration septum, and separate venting has been commonly utilized, such as that provided by self-venting filters or by a separate needle.

0006While self-venting filters/needles have been intended to allow safe use of multi-dose or unit dose vials by trapping aerosols released when the access needle is withdrawn from the septum, the use of this separate component, along with the others needed to actually have a drug available to deliver, increased the cost and time of preparation.

0007Self-dispensing (i.e., piggy-back) bottles has been another heretofore suggested approach. Bottles of this type have normally contained only enough drug for a single dose, and the drug has usually been reconstituted using a separate source of diluent and preparative supplies. When the drug has been reconsituted in such a bottle, the bottle itself has then served as the dispensing reservoir for the dose, with such dispensing being normally under gravity flow.

0008A still different approach heretofore suggested was utilization of a partial-fill bag wherein the bag contains diluent. Separate supplies have normally been used to reconstitute the drug, which was then added to the partially filled bag, to make a unit dose. In a sophistication of this approach, a dry drug vial has been utilized with the vial attached to a special partial-fill bag to eliminate the need for preparation supplies and extra diluent.

0009To save preparation time, it has also been suggested that bags be provided that are pre-filled with drug solution, usually to be stored frozen. Another unit dose pre-fill approach that has been suggested was a pre-filled syringe cartridge which contains drug solution. A drug pre-fill has also been suggested containing a drug which could be inserted into a special patient-activated delivery pump.

0010All of the unit dose approaches, however, have had the clear limitation of being applicable only to those drugs which are given in the same dose (i.e., quantity of drug), or within a very small range of doses, to most patients. It can therefore be appreciated that multi-dose packaging, on the other hand, can present substantial advantages if the contents can be custom-dispensed without significant labor input.

0011A major problem with any liquid pre-fill, however, regardless of whether delivery is intended as a unit dose or a multi­dose, is that such pre-fills have heretofore been commonly limited either to those drugs which are stable at room temperatures or are frozen. This can be overcome, however, by the use of dry or binary (dry chamber plus diluent chamber) packaging forms, since such packaging allows continued separation of the drug components until near the time of use, at which time the components can be mixed and dispensed. This clearly is advantageous, particularly where the components should not (or perhaps in some case cannot) be mixed until quite near the time of intended use, such as, for example, where the reconstituted drug has a short shelf-life.

0012With respect to prior art patents, U.S. Patent No. 3,938,520 is directed to a mixing device having a vented transfer unit wherein the contents of a medicament storage receptacle can be mixed with the contents of a diluent storage receptacle with the lower positioned diluent storage receptacle being vented through the transfer unit positioned above the diluent storage unit, and with a syringe being mentioned for withdrawal of the mixture from the diluent stage receptacle, while still in the upright position, through the transfer unit.

0013U.S. Patent No. 3,125,092 is directed to a device for supplying an additive material to a solution in an infusion flask by withdrawing solution from the infusion flask through a needle using a rubber ball positioned between the needle and container holding the additive material, mixing the withdrawn solution with additive material in the additive container, and then exerting positive pressure to return the mixture through the needle to the infusion flask.

0014U.S. Patent No. 4,410,321 is directed to a closed drug delivery system wherein the diluent is within a bag and is mixed at the bag with a substance stored in a separate container prior to use.

0015U.S. Patent No. 3,337,041 is directed to a disposable syringe wherein material, in solid state within the syringe, is mixed in the syringe with liquid material withdrawn from a storage receptacle by insertion of the nozzle end of the syringe into the storage receptacle.

0016U.S. Patent No. 1,929,616 is directed to a double compartment ampule wherein two substances are mixed within the ampule by repositioning a divider between the compartments separately storing the substances.

0017U.S. Patent No. 3,881, 640 is directed to a measuring means for reconstituted substances with the device having an air vent filter connected therewith for venting air from the top portion of the measuring means. U.S. Patent No. 3,938,520, discussed above, also includes a filter included in the air vent passage above the receptacle being vented.

0018As can be appreciated from the foregoing, while various devices and methods have heretofore been suggested and/or utilized for handling of various substances, including handling of drugs with mixing of such drugs being included in such handling, such devices and methods have not proved to be completely successful, at least in some cases, in providing a device and method for handling subtances, such as drugs, particularly where such drugs are to be used in individualized doses, are to be mixed just prior to use, and/or are to be prepared and utilized with minimum labor, minimum chance of error occurrence, and maximum safety.

0019This invention provides an improved device and method for handling subtances, and particularly drugs, with individualized dosage being made possible, with mixing occurring just prior to use, with labor and the chance of error occurrence being minimized, and with safety being maximized.

0020In this invention, the delivery receptacle is provided with an actuator therein, and has a first substance, such as a diluent, inserted into the delivery receptacle. The first substance in the delivery receptacle is moved by positive flow, due to actuation of the actuator in the delivery receptacle, through a vented filter-containing transfer unit to a storage receptacle having a second substance, such as a drug, therein for mixing thereat. The mixture is thereafter withdrawn by actuation of the actuator and caused to flow through the transfer unit to the delivery receptacle, with delivery of the mixture from the delivery receptacle being thereafter caused by actuation of the actuator, after the storage receptacle and transfer unit have been removed from the delivery receptacle.

0021This invention resides in the novel construction, combination, arrangement of parts and method substantially as hereinafter described, and more particularly defined by the appended claims, it being understood that changes in the precise embodiment of the herein disclosed invention are meant to be included as within the scope of the claims.

0022The accompanying drawings illustrate a complete embodiment of the invention according to the best mode so far devised for the practical application of the principles thereof, and in which: <ul id="ul0001" list-style="none"><li>FIGURE 1 is a perspective view of a sealed package utilized to package components until use;</li><li>FIGURE 2 is a side view of a diluent storage receptacle shown in FIGURE 1 as one of the packaged components;</li><li>FIGURE 3 is a side view of a drug storage receptacle shown in FIGURE 1 as one of the packaged components;</li><li>FIGURE 4 is a perspective view of the storage receptacle having a transfer unit mounted thereon;</li><li>FIGURE 5 is an enlarged perspective view illustrating primarily the transfer unit shown in FIGURE 4;</li><li>FIGURE 6 is a sectional view taken through line 6-6 of FIGURE 5 and illustrating the transfer unit in greater detail;</li><li>FIGURE 7 is a perspective view of a syringe and diluent storage receptacle illustrating insertion of diluent into the delivery receptacle;</li><li>FIGURE 8 is a perspective view of a syringe and drug storage receptacle illustrating insertion of diluent from the delivery system into the drug storage receptacle for mixing thereat;</li><li>FIGURE 9 is a perspective view of a syringe and drug storage receptacle illustrating withdrawal of the mixture from the storage receptacle into the delivery receptacle; and</li><li>FIGURE 10 is a perspective view illustrating typical use of the delivery receptacle in delivering a reconstituted drug to a patient.</li></ul>

0023Referring to FIGURE 1, a sealed package 12 is illustrated containing the components, or elements, needed for utilization, with the components to be provided to a user being therefore within a sealed envelope which can be left intact until needed for use.

0024As indicated in FIGURE 1, when package 12 is used to package drug components, the package can typically include a delivery receptacle 14, a first substance storage receptacle 15, and a second substance storage receptacle 16. When so provided, the receptacles are preferably held in spaced relationship with respect to one another with the package being sealed around edges 18 by conventional means, and with sealed pockets also being preferably formed around each component to separately hold each component within a separate compartment, which compartments are formed by seals 19.

0025The packaging material can be conventional, and can be, for example, sealable foil material. When sealed (as by conventional heat sealing, for example), the package forms a vapor-barrier envelope to maintain the components in a sterile, dry environment until the package is opened, typically at the time of intended use.

0026While the package shown herein contains three specific receptacles, it is meant to be realized that the number and form of the receptacles can be varied as needed for a particular use, and the invention is not meant to be limited thereto.

0027First substance storage receptacle 15 is shown in greater detail in FIGURE 2, while second substance storage receptacle 16 is shown in greater detail in FIGURE 3. As can be appreciated, these receptacles can be identical and may be, for example, vials of any suitable material, such as again by way of example, glass, polypropylene, polyethylene, or laminates. Each vial 15 and 16 has a body portion 20 defining a storage chamber, or reservoir, 21, which retains the desired substance, such as a diluent 22 (as indicated in FIGURE 2) or a drug 23 (as indicated in FIGURE 3) where a drug is to be mixed with diluent to reconsitute the drug.

0028Each vial 15 and 16 has a transfer unit 25 connected therewith, and the transfer units may be identical, with transfer unit 25 being shown in greatest detail in FIGURES 4 through 6.

0029As best shown in FIGURES 4 through 6, transfer unit 25 includes upper and lower body portions 26 and 27. Lower body portion 27 has disk 28 mounted thereon, which disk is of a size to span and cover aperture 30 defined by upper annular lip 31, which lip forms the mouth of the vial (i.e., vial 15 or 16 with vial 16 being illustrated in FIGURES 4 through 6).

0030Disk 28 preferably has a depending shoulder 32 which snugly fits over the outer wall of lip 31. If desired (and as shown), a clamp ring 34 may be provided around the edge of disk 28 and outwardly directed shoulder 35 of the vial to hold the transfer unit against and over the mouth of the vial (alternately, welding could be utilized if the vial is formed of plastic material), and a gasket ring 36 may be positioned between lip 31 of the vial and the inner surface of disk 28 to assure establishment of a seal therebetween.

0031Transfer unit 25 may be formed of any suitable material, such as plastic, for example, and has a central bore 38 therethrough. Bore 38 has an inner port 39, which inner port opens through disk 28 into the reservoir formed within the storage receptacle, and an outer port 40, at upper body portion 26, with outer port 40 being preferably adapted to receive a portion 42 of delivery receptacle 14 having an opening 43 therein in order to establish communication, through bore 38, between the storage receptacle reservoir and the compartment, or reservoir, 44 in delivery receptacle 14.

0032As specifically shown in FIGURES 1 and 7 through 9, delivery receptacle 14 is embodied as a syringe with compartment 44 being formed by syringe body 45. End, or nozzle, portion 42 of syringe 14 is preferably tapered, and is snugly received in port 40 of transfer unit 25 so that the long and preferably elastomeric insert of end portion 42 forms a seal with the inner walls of port 40 (as indicated in FIGURE 6).

0033Lower, or main, body portion 27 of transfer unit 25 has a vent passage, or bore, 47 therein, which vent passage has an inner conduit 48 with port 49 at the inner end thereof, which port opens through disk 28 into the reservoir of the storage receptacle. As shown in FIGURE 6, conduit 48 of vent passage 47 is parallel to, but radially offset from, central bore 38 so that ports 39 and 49 are adjacent to, but spaced from, one another. The openings into the reservoir are preferably flash-free.

0034The outer conduit 51 of vent passage 47 extends outwardly, at substantially a right angle, from the end of conduit 48 so that conduit 51 opens to the side of main body portion 27 of the transfer unit. As best shown in FIGURE 6, the outer portion 52 of conduit 51 has an enlarged diameter relative to the remainder of the conduit, and is of a sufficient size to snugly receive filter 53 therein.

0035Filter 53 is a two-way filter that is air permeable (but is impermeable to liquid and solid materials), with the filter being a hydrophobic (rather than hydrophilic), sterile bacterial filter having, for example, a 0.22 micron pore size.

0036Cap 55 (as best shown in FIGURE 4) is provided at the end of port 40 at the outer end of central bore 38, and lugs 56 (as best shown in FIGURE 5) are provided to releasably lock the cap in position to seal the central bore. In addition, plug 58 is provided for insertion into the vent outer port formed at the end of enlarged bore conduit 52 outwardly of filter 53. When in position in the end of the vent passage (as indicated in FIGURE 4), a seal is provided thereat. As indicated, plug 58 may also have a retainer strap 59 thereon for retaining the plug adjacent to the transfer unit when the plug is withdrawn from the position sealing the end of the vent passage (as indicated in FIGURE 5).

0037Delivery receptacle 14 has an actuator 61 therein for causing positive movement of the stored substance to achieve mixing, and then later, delivery of the mixture. As specifically shown in FIGURES 7 through 9, actuator 61 can be a piston within syringe body portion 45, and piston 61 is actuated by rod 62, the outer end portion 63 of which rod extends from the rear end of the syringe (i.e., opposite to that of front, tapered end 42).

0038In preparing a package, storage receptacles 15 and 16 (if utilized) are pre-filled (with diluent and a drug, for example) and a transfer unit 25 is connected with each of the receptacles to seal the same material needed. A syringe, with a cap 65 on the tapered end portion 42, is also provided, and the components are positioned in the package, and the package then sealed, as indicated in FIGURE 1. The package is then retained in sealed condition, preferably until needed for use. The components used in the package may be varied, as described above and/or, for example, the syringe may be filled with one of the substances (such as diluent) which would then allow one of the storage receptacles to be deleted from the package.

0039To use the package, the user opens the package and, using sterile procedures, attaches the deliver component (a syringe as specifically described herein) to the diluent vial 15, after removing the connector cap 55 of the vial. Vent plug 58 is also removed, and after inverting the syringe and vial, as indicated in FIGURE 7, the diluent is drawn from the vial into the syringe by moving piston 61 rearwardly within syringe body 45. Vent 47 allows air to enter vial 15 through filter 53, thus preventing a vacuum from forming and hindering diluent removal.

0040When syringe 14 is filled with diluent (or alternately when using a syringe having diluent already stored in the syringe), the user removes cap 55 and vent plug 58 from drug vial 16, and attaches the filled syringe to transfer unit 25 on drug vial 16. The user then injects the diluent from syringe 14 into vial 16, as indicated in FIGURE 8, by moving the piston within the syringe body forwardly (toward the nozzle of the syringe), to mix the contents to dissolve the drug (which drug is preferably in solid form but could be in liquid form) in the liquid diluent. Filter 53 in vent 47 allows air in the vial to escape, and thus prevents pressure entrapment. Vent 47 also allows gaseous by-products of the solvating reaction (if any) to escape without contaminating the user with aerosol of drug, which might be hazardous to the user.

0041After shaking vial 16, if necessary, to completely dissolve the drug (if in solid form), and after inverting the syringe and vial, as indicated in FIGURE 9, the user then draws the contents of vial 16 into syringe 14 by actuation of syringe piston 61 rearwardly within syringe body 45 (i.e., piston 61 is moved in the axial direction opposite to that of the initial movement). The vent on the drug vial now allows sterile air to enter the vial and the liquid in the vial to be drawn into the syringe.

0042The syringe is now filled with reconstituted drug solution, and the user removes syringe 14 from transfer unit 25 (and hence also from drug vial 16) and may, at this time, dispose the emptied vials and transfer units.

0043The syringe with the reconstituted drug therein may then be utilized as, for example, by connecting the syringe through a secondary fluid access port 66 (unused secondary fluid access ports are maintained closed), to primary fluid conduit 67, which primary conduit can be connected to deliver a primary fluid therethrough (as is conventional), as indicated in FIGURE 10. As shown, tube 67 extends to needle 68 insertable into a member (such as arm 69) of a patient. Syringe 14 may be manually operated, or, preferably, may be inserted into a delivery control device 70, which device is connected with outer portion 63 of rod 62 to control actuation of piston 61 to thereby achieve individualized dose administration to a patient. Such a delivery control device is shown in European Application No. 86106427.7 published December 17, 1986.

0044As can be appreciated from the foregoing, this invention provides an improved apparatus and method for handling substances, and particularly drugs.