WO2001052917A2

WO2001052917A2 - Medicament dispenser and cooperating reservoir fill assembly

Info

Publication number: WO2001052917A2
Application number: PCT/US2001/001854
Authority: WO
Inventors: Marshall S. Kriesel
Original assignee: Science Incorporated
Priority date: 2000-01-21
Filing date: 2001-01-19
Publication date: 2001-07-26
Also published as: WO2001052917A3; AU2001227964A1

Abstract

A fluid dispenser (30) for use in controllably dispensing beneficial agents to a patient and a co-operating reservoir fill assembly (32) for controllably filling the fluid reservoir (35) of the fluid dispenser (30). Disposed within the fluid dispenser (30) is a novel stored energy source that is provided in the form of an expandable, elastomeric member (50) that provides the force necessary to continuously and substantially uniformly expel fluid from the fluid dispenser (30) over time.

Description

MEDICAMENT DISPENSER AND COOPERATING RESERVOIR FILL ASSEMBLY

S P E C I F I C A T I O N

Background of the Invention

This is a Continuation-In-Part of co-pending application Serial No. 09/060,858 filed April 15, 1998 which is a Continuation-In-Part of co-pending application Serial No. 08/473,650 fiSed June 6, 1995 which has issued into Patent No. 5,743,879 which is a Continuation-In-Part of copending application Serial No. 08/349,496 filed December 2, 1994 now abandoned in U.S.

Field of the Invention

The present invention relates generally to fluid medicament dispensers. More particularly, the invention concerns a dispenser for use in controllably dispensing a liquid medicament and a cooperating medicament fill assembly including a closed end vial component for filling the reservoir of the dispenser.

Discussion of the Prior Art

Traditionally, conventional syringes are used to inject many beneficial agent solutions such as insulin. In accordance with conventional procedures, the prescribed dose is first drawn into the syringe and a visual check is made to make certain that the correct amount of insulin is present in the syringe. Next, air is expelled from the syringe and the dose is injected manually.

These conventional procedures have numerous drawbacks including adverse reaction caused by the bolus injection of drugs by hand via a syringe. In the majority of cases, the adverse reactions are not due to the drug. tself, but rather are due to an improper dosing rate of injection of the drug. In many therapeutic situations, the contents of a syringe should be delivered over a number of minutes or hours, However, in clinical practice, this rarely occurs due to time pressure on the medical professional staff who must operate the syringe manually.

Because diabetics generally require regular and repeated injections of insulin, the use of multiple injections from self-delivering devices, such as conventional syringes, is cumbersome, time consuming, and dangerous if not properly performed. In addition, the process of sticking one's self and infusing the liquid medicament can be extremely unpleasant for the medically untrained. For this reason, several types of dispensing devices have been suggested for automatically dispensing a predetermined quantity of a liquid medicament such as insulin from a multi-dose container. Exemplary of such devices are those described in European Patent Application No. 37696 and in U.S. Patent No. 4,592,745 issued to Rex, et al. Both of the aforementioned devices dispense a predetermined quantity of liquid from a liquid reservoir or container and both include mechanical operating mechanisms for expelling the fluid from the reservoir.

The Rex, et al device comprises an elongated body formed from two separable sections one of which contains an operating mechanism and the other of which contains a prefilled cartridge.

The operating mechanism of the device mechanically advances an axially movable piston rod which, in turn, drives a piston plug located inside the cartridge so as to expel fluid from the device via a needle located at the bottom end of the body. The piston rod advances in successive axial steps of fixed length through rotation of a rotatable piston rod nut. The piston rod nut is driven by a rotatable worm, which is rotated by the ad- . vancing axial movement of a pressure device located at the top of the elongated body.

The EPO application discloses a dispensing device somewhat similar to the Rex, et al. device, but embodies an operating mechanism that comprises a pawl which permits relative movement of a ratchet-toothed member in a substantially rectilinear arrangement. As in the Rex, et al. device, the operating mechanism drives the plunger of a medicament vial to expel fluid therefrom.

U. S. Patent No. 4,813,937 issued to Vaillancourt discloses an infusion system in which the inflow of fluid into the device causes an elastomeric member attached to a piston to be moved so as to stretch the elastomeric member. The thusly tensioned elastomeric member provides the source of energy to expel the fluid from the device when the outlet tubing of the system is opened. However, as is clear from a study of the Vaillancourt patent, the device disclosed therein operates in a substantially different manner than the device of the present invention.

Electrically operated syringe pumps are also well known, however, they are typi- cally of considerable complexity and are designed to inject very small doses of medicine with considerable accuracy over a long period, which may be up to 24 hours. Such syringe pumps do not provide the inexpensive, simple and manually operated device suitable for the slow injection of drugs over a shorter period of time, which may range from one to 15 minutes.

Many of the prior art medicament dispensing devices are of complex construction and, therefore, are often very expensive to manufacture. Additionally, such devices tend to be somewhat unreliable in use and frequently have a limited useful life. In using certain of the prior art devices, maintaining sterility has also proven to be a problem.

As will be appreciated from the discussion which follows, the apparatus of the present invention uniquely overcomes the drawbacks of the prior art by providing a novel, disposable dispenser of simple but highly reliable construction. A particularly important aspect of the apparatus of the present invention resides in the provision of a novel, self-contained energy source that provides the force necessary to uniformly and precisely dispense solutions, such as insulin, from containers that can be conveniently loaded into the apparatus. Because of the simplicity of construction of the apparatus of the invention, and the straight-forward nature of the energy source, the apparatus can be manufactured . at low cost without in any way sacrificing accuracy and reliability.

Somewhat similar medicament dispensers are disclosed in U. S. Patent No. 5,743,879 and 5,993,421 issued to the present inventor. Because the present application is directed toward improvements of the inventions disclosed in these applications, Patent Nos. 5,743,879 and 5,993,421 are hereby incorporated by reference as though fully set forth herein. As will be discussed in detail hereinafter, the present invention includes novel field filling means for use with devices similar to those disclosed in the aforementioned patents to fill the fluid reservoirs of the devices. Other somewhat similar medicament dispenser are disclosed in co-pending Serial No. 09/060,858 which was filed by the present inventor on April 15, 1998. Serial No. 09/060,858 is also incorporated by reference as though fully set forth herein. Summary of the Invention

It is an object of the present invention to provide a small, compact fluid dispenser for use in controllably dispensing fluid medicaments; hormones, such as insulin; or other diabetes related agents; antibiotics; oncolytics; analgesics, bio-pharmaceutics, other inject- able therapeutics, and related diagnostic agents, and the like and a cooperating reservoir fill assembly for controllably filling the fluid reservoir of the fluid dispenser.

Another object is to provide a device of the aforementioned character which is of very simple construction and embodies a minimum number of parts.

Another object of the invention is to provide a disposable small fluid dispenser component which is compact and easy to fill using the novel reservoir fill assembly of the invention.

Another object of the invention is to provide a fluid dispenser component within which a stored energy source is provided in the form of an expandable, elastomeric member of novel construction that provides the force necessary to continuously and substantially uniformly expel fluid from the dispenser component.

Another object of the invention is to provide a fluid dispenser component of the class described which includes a fluid flow control assembly that filters and precisely controls the flow of the medicament solution from the reservoir of the dispenser container.

Another object of the invention is to provide a novel reservoir fill assembly for use in filling the fluid reservoir of the fluid dispenser which fill assembly is compact, easy to use and is of simple construction.

Another object of the invention is to provide an apparatus of the aforementioned character in which the reservoir fill assembly comprises a closed end vial assembly that can be prefilled with a wide variety of medicinal fluids.

Another object of the present invention is to provide a reservoir fill assembly of the type described in the preceding paragraph in which the prefilled vial assembly is housed within a novel adapter assembly which is readily mateably with the fluid dispensing apparatus for controllably filling the reservoir thereof.

Another object of the invention is to provide a fluid dispenser and cooperating reservoir fill assembly of the class described which is lightweight, is easy for ambulatory patients to use, is fully disposable, and is extremely accurate so as to enable the infusion of precise doses of medicaments such as morphine over prescribed periods of time.

Another object of the invention is to provide an easy-to-use medicament dispenser and cooperating reservoir fill assembly which is extremely durable and highly reliable in use.

Another object of the invention is to provide a dispenser of the class described which accepts a vial assembly that contains a lyophilized drug.

Brief Description of the Drawings

Figure 1 is a generally perspective, exploded view of one embodiment of the fluid dispensing apparatus and reservoir fill assembly of the present invention.

Figure 2 is a top plan view of the assembled apparatus shown in figure 1. Figure 3 is a view taken along lines 3-3 of Figure 2.

Figure 3A is a greatly enlarged, cross-sectional view of the area designated as 3A in Figure 3.

Figure 3B is a greatly enlarged, cross-sectional view of the area designated in figure 3 as 3B.

Figure 4 is a top plan view of the fluid dispensing apparatus

Figure 5 is a cross-sectional view taken along lines 5-5 of Figure 4.

Figure 5A is a cross-sectional view of an alternate form of the fluid dispensing apparatus having a different type of infusion means.

Figure 5B is a generally perspective, foreshortened view of an apparatus of the type shown in figure 5A, but having a slightly differently configured cannula.

Figure 5C is a greatly enlarged view of the section of delivery line designated as 5C in figure 5B.

Figure 6 is a cross-sectional, exploded view of the fluid dispensing apparatus shown in figure 5.

Figure 6A is a view taken along lines 6A-6A of figure 6.

Figure 7 is a view taken along lines 7-7 of Figure 6.

Figure 8 is a view taken along lines 8-8 of Figure 6. Figure 9 is a view taken along lines 9-9 of Figure 6.

Figure 10 is a generally perspective, exploded view of an alternate form of the apparatus of the invention.

Figure 11 is a side-elevational, cross-sectional view of the apparatus shown in figure 10.

Figure 11A is a cross-sectional view taken along lines 11A-11A of figure 11.

Figure 12 is a top plan view of the adapter portion of the fill assembly of the apparatus of the invention.

Figure 13 is an end view of the adapter portion shown in Figure 12.

Figure 14 is a cross-sectional view taken along lines 14-14 of Figure 12.

Figure 14A is a cross-sectional view taken along lines 14A-14A of Figure 14.

Figure 14B is an exploded view illustrating the individual components shown in Figure 14A.

Figure 15 is a top plan view of the fluid dispensing component of the apparatus shown in Figure 10.

Figure 16 is a cross-sectional view taken along lines 16-16 of Figure 15.

Figure 17 is a cross-sectional view of the field fill portion of the reservoir fill assembly of the apparatus of this latest form of the invention.

Figure 18 is a view taken along lines 18-18 of Figure 17.

Figure 19 is a cross-sectional view, similar to Figure 17 showing the field fill portion being filled using a conventional syringe.

Figure 19A is a greatly enlarged, cross-sectional view of the area designated as 19A in Figure 19.

Figure 20 is a generally perspective, exploded view of still another form of the fluid dispensing and reservoir fill assembly of the invention.

Figure 21 is a generally perspective view of the container component of the alternate reservoir fill assembly shown in Figure 20, partly broken away to show internal construction.

Figure 22 is an enlarged, cross-sectional view of the apparatus shown in Figure 1.

Figure 23 is a cross-sectional view taken along lines 23-23 of Figure 22.

Figure 24 is a side view of the pusher component of the reservoir fill assembly shown in Figure 20.

Figure 25 is a cross-sectional view taken along lines 25-25 of Figure 24.

Figure 26 is a cross-sectional view of the container component of the alternate reservoir fill assembly shown in Figure 20.

Figure 27 is generally perspective, fragmentary view of still another embodiment of the invention.

Figure 28 is a view taken along lines 28-28 of figure 27.

Figure 29 is a view taken along lines 29-29 of figure 27.

Description of the Invention

Referring to the drawings and particularly to Figures 1 through 9, one embodiment of the dispensing apparatus of the invention is there shown and can be seen to comprise a fluid medicament dispenser and a cooperating reservoir fill means for filling the reservoir of the dispensing apparatus. In Figure 1, the medicament dispenser is shown fully assembled and is generally designated by the numeral 30. The reservoir fill means or fill assembly, on the other hand, is shown in exploded form and is generally designated in Figure 1 by the numeral 32. The medicament dispenser 30 is of the same general character as that described in U.S. Serial No. 08/473,650 which application is incorporated herein by reference.

As best seen in Figures 3, 4, 5, and 6 the medicament dispenser 30 of the present form of the invention comprises a housing assembly including a housing or container 34, having a first open end 34a and a closed end 34b (Figure 6). End 34b is closed by an end wall 34c having a centrally disposed socket like portion 34d. Received within a reservoir- defining chamber 34e of housing 34 is the important stored energy means of this form of the invention, the purpose of which will presently be described.

First end 34a of housing 34 is closed by a fill and dispensing means for first permitting reservoir 34e to be filled with fluid by reservoir fill means via a reservoir inlet 35 (Figure 3) by means of the reservoir fill assembly and then for dispensing fluid from the filled reservoir to the patient via a reservoir outlet. The fill and dispensing means here comprises a dispensing head assembly generally designated in the drawings by the numeral 38. As best seen in Figure 3, assembly 38 includes a closure cap 40 which is receiv- able over housing 34 to sealably close open end 34a thereof. Disposed within cap 40 is a flow control means for controlling the outward flow of fluid flowing from the reservoir or internal chamber 34e of container 34 toward the reservoir outlet. The flow control means of this embodiment of the invention comprises flow control elements including a porous flow rate control wafer 44 and a porous filter wafer element 46 (Figure 6) . Wafers 44 and 46 are held in position within cap 40 by means of retainer plate 47 having a plurality of fluid delivery apertures 47a (Figure 9) .

Disposed within reservoir 34e of the housing or container 34 is the previously mentioned stored energy means of the invention, which functions to controllably urge fluid contained within the reservoir outwardly of the device via the flow control means. This unique stored energy means here comprises a specially configured elastomeric shaped article member 50 which is compressively deformable from the, first, partially compressed configuration shown in Figure 5 to a second, more compressed configuration shown in Figure 3 wherein it has a tendency to return toward its first configuration. As best seen in Figure 6, article 50 comprises an elongated compressible member having a plurality of longitudinally spaced apart grooves and ridges 50a and 50b respectively. It is to be understood that in some instances member 50 may be substantially uncompressed in its starting configuration. In a manner presently to be described, member 50 acts upon an elastomeric stopper 51 which is sealably carried within reservoir 34e to deliver the beneficial agent to the patient.

As discussed in U. S. Serial No, 08/473,650, which is incorporated herein by reference, the stored energy means can be constructed from a wide variety of materials including rubbers, polymers and other thermoplastic elastomers (TPE) and thermoplastic urethane (TPU) . By way of example, suitable materials include latex rubber, rubber polyolefins, polyisoprene (natural rubber), butyl rubber, nitrile rubber, polyurethane, vinyls, vinyl-end-blocked polydimethylsiloxanes, other homopolymers, copolymers (random alternating, block, graft, cross-link and star block), silicones and other flouro- polymers, mechanical poly-blends, polymer alloys and interpenetrating polymer networks.

Turning particularly to Figures 1 and 3, the present form of the novel reservoir fill assembly 32 of the invention can be seen to comprise a container subassembly 54 and an adapter subassembly 56. Container subassembly 54 includes a container such as a vial 57 which contains the medicinal fluid "F" with which the reservoir of the dispensing apparatus is to be filled. Adapter subassembly 56 functions to interconnect the reservoir fill assembly with the medicament dispenser in a manner such that fluid can be transferred from container 57 to reservoir 34e of the dispenser component. As will presently be described, this fluid transfer is accomplished by urging container subassembly 54 forwardly into the adapter subassembly 56.

As best seen in Figure 3, container 57 has a first open end 57a that is sealably closed by an elastomeric plunger assembly 60 and a closed second end 57b. Plunger assembly 60 includes a body portion 60a that sealably engages the inner surface of container 57 and a threaded connector portion 60b. In the manner indicated in Figure 3, container 57 is telescopically receivable within an annular space 62 formed between the inner surface of housing 64 of adapter subassembly 56 and a pusher member 66 that is disposed interiorly of housing 64. Pusher member 66 includes a body portion 66a and a head portion 66b that is internally threaded to receive threaded connector portion 60b of plunger assembly 60. Pusher assembly 66 also includes a hollow cannuia 68 that extends longitudinally of body portion 66a. With this construction, when plunger assembly 60 is threadably interconnected with pusher member 66 in the manner shown in figure 3 when container 57 is pushed inwardly of housing 64, the outboard end of hollow cannuia 68 will pierce a central wall 60c formed in body portion 60a of plunger assembly 60 thereby opening fluid communication between the fluid chamber 57c of container 57 and the internal passageway of hollow cannuia 68. An inward pressure exerted on container 57 will then urge the fluid contained within fluid chamber 57c to flow into hollow cannuia 68 and then into chamber 70a formed in valve retainer disk 73 which forms a part of adapter assembly 56. Chamber 70a houses a conventional umbrella check valve 72 that forms a part of the fluid flow control means of the

reservoir fill assembly. Check valve 72 controls fluid flow toward and away from the fluid dispenser 30. As container 57 is pushed inwardly, fluid under pressure will then flow past umbrella check valve 72 into a passageway 74 formed in valve retainer disk 73 and then into the internal passageway of a piercing cannuia 76 that also forms a part of connector adapter 70. It is to be understood that the fluid contained within chamber 57c can take various forms as, for example, antibiotics, oncolyties, anagesics, cardiac agents, biophar- maceutics and diagonic fluids.

When the reservoir fill assembly 32 of this latest form of the invention is mated with closure cap 40 of the fluid dispenser in the manner shown in Figure 3, cannuia 76 will pierce a pierceable septum 78 which is carried by closure cap 40 thereby permitting fluid to flow into reservoir 34e of the fluid dispenser via a passageway 79 which communicates with reservoir inlet 35. Under some circumstances, it may be desirable to place a check valve in the reservoir inlet to prevent fluid backflow. When operating at elevated reservoir pressures

Prior to use, the ends of fill assembly 56 are substantially sealed by sterile barrier members 83 and 85. Similarly, container subassembly 54 is sealably closed by previously bonded, sterile barrier member 87 while closure cap 40 of the fluid dispenser is closed by a barrier member 91 (Figure 1) .

To interconnect reservoir fill assembly 32 with fluid dispenser 30, connector adapter 70 is provided with circumferentially spaced bayonet locking ears 92 which are lockably received within the circumferentially spaced slots 94 formed in dispensing head assembly 38 (Figure 1 and 3) . Relative rotation of the reservoir fill assembly and the fluid dispenser component will then effect a sterile interconnection between the reservoir fill assembly and the fluid dispenser. An O-ring 31 is disposed between housing 38 and connector adapter 70 to prevent fluid leakage between the components and also to prevent seizing of the components. As the reservoir fill assembly is thus aseptically mated with the fluid dispenser, cannuia 76 of the reservoir assembly will pierce pierceable septum 78 which is mounted within closure cap 40 and held in place by septum retaining ring 80. This done, an inward pressure exerted on container 57 will cause the fluid "F" to flow into cannuia 68, past check valve 72, into passageway 74, into cannuia 76, into passageway 79 and thence into reservoir 34e via reservoir inlet 35.

As the fluid under pressure flows Into chamber 34e of the dispensing apparatus, the stored energy means, or member 50, will be compressed by stopper member 51 causing internal stresses to be built up within the member, which stresses tend to return the mem- ber along with stopper 51 toward the first configuration. With reservoir 34e thusly filled, the delivery means of the invention can be used to deliver fluid within reservoir 34e from the fluid dispenser. The delivery means here comprises a protective sheath 95a, which covers infusion cannuia 97 (Figure 3) . Sheath 95a can be broken away from needle housing body 95 so that the infusion cannuia be appropriately inserted into the vein of the patient to commence the controlled delivery to the patient of the fluid contained within reservoir 34e via the flow control means of the invention. Connector wings 99 are provided on needle housing body 95 which is connected to dispensing head 38 so that the device can be connected to the patient's body by means of an adhesive provided on the lower surfaces of wings 99. It is to be understood that cannuia 97 can protrude from housing body 95 at various angles depending upon each use to be made of the device.

Turning next to figures 5A and 5B an alternate form of medicament dispenser is there shown. This form of the invention is similar to that shown in figure 5 and like numerals are used to identify like components. The principal ^'difference between the embodiment shown in figure 5 and that shown in figures 5A and 5B resides in the differently configured infusion means for infusing medicinal fluids into the patient. This infusion means here comprises an administration line assembly generally designated by the numeral 101. Assembly 101, which takes the place of sheath 95a and infusion cannuia 97, includes an elongated infusion line 101a which is connected at one end to dispensing mounting assembly 38 and has at its opposite end a conventional subdermal needle assembly 101b which is of a character well known to those skilled in the art. Disposed intermediate the ends of line 101a is a conventional Y-site 101c which permits access to line 101a. In one form of the invention, the Y-site, which comprises a part of the delivery means of the invention, is provided with a pierceable septum lOld (figure 5A) that permits access to line 101a through use of a conventional syringe and provides bolus means for introducing a bolus dose into line 101a.

Referring to figure 5C, another flow control means is there shown. This flow control means here comprises a microbore section 100 having a capillary inside diameter bore 100a, which precisely controls the rate of fluid flow toward needle assembly 101b.

Turning next to Figures 10 through 19, an alternate embodiment of the dispensing apparatus of the invention is there shown and generally designated by the numeral 102. This form of the invention is similar in some respects to the earlier described embodiment and like numerals are used^' to identify like components. As best seen in figures 10 and 11, this latest form of the invention can be seen to comprise a fluid medicament dispenser 30 which is identical to that previously described and a cooperating reservoir fill means for filling the reservoir of the dispensing apparatus which is of a different configuration. More specifically, the reservoir fill means or fill assembly, which is generally designated by the numeral 104, enables the fill assembly to be conveniently filled in the field.

As best seen in Figures 10, 11, 15 and 16 the medicament dispenser 30 of this latest form of the invention comprises a housing assembly including a housing or container 34, having a reservoir-defining chamber 34e within which the stored energy means of the invention is disposed . As before, housing 34 is closed by a fill and dispensing means for first permitting reservoir 34e to be filled with fluid by reservoir fill means via a reservoir inlet 35 by means of the reservoir fill assembly and then for dispensing fluid from the filled reservoir to the patient via a reservoir outlet.

Turning particularly to Figures 10, 11 and 17 through 19, the novel reservoir fill assembly 104 of this latest form of. the invention can be seen to comprise a container subassembly 106 and an adapter subassembly 108. Container subassembly 106 is somewhat similar in construction to container subassembly 54 but includes an open-ended container - 110 which can be filled in^* the field with a medicinal fluid "F" which is then used to fill the reservoir of the dispensing apparatus. As before adapter subassembly 108 functions to interconnect the reservoir fill assembly with the medicament dispenser in a manner such that fluid can be transferred from container 110 to reservoir 34e of the dispenser component.

As best seen in Figure 17, container 110 has a first open end 110a that is sealably closed by a pierceable septum 112 and a second end 110b. Disposed within container 110 is a plunger assembly 116 that includes a body portion 116a that sealably engages the inner surface of container 110 and a threaded connector portion 116b. In the manner indicated in figures 17 and 19, during the field filling step, which will presently be described, plunger assembly 116 is telescopically mov/abie within container 110 from the first position shown in figure 17 to the second position shown in figure 19. Container 110 is mounted within a toothed sleeve 120 which has a proximal end 120b and a distal end 120c. End 120b includes a tear-away cap 120d with a vent patch 114 and is telescopically receivable within an annular space 123 formed between the inner surface of a housing 124 of adapter subassembly 108 and a pusher member 126 that is disposed interiorly of housing 124 (figures 11 and 14). Pusher assembly 126 includes a body portion 126a and a head portion 126b that is internally threaded to receive threaded connector portion 116b of plunger assembly 116 (figures 11 and 14). Pusher assembly 126 also includes a hollow cannuia 128 that extends longitudinally of body portion 126a. With this construction, when plunger assembly 116 is threadably interconnected with pusher member 126 in the manner shown in figure 11 when container subassembly 106 is pushed inwardly of housing 124, the outboard end of hollow cannuia 128 will pierce a central wall 116c formed in plunger 116 thereby opening fluid communication between the fluid chamber 110c of container 110 and the internal passageway of hollow cannuia 128. An inward pressure exerted on container subassembly 106 will then urge the fluid contained within fluid chamber 110c to flow into hollow cannuia 128 and then into a chamber 130a formed in valve retaining disk 1 30b which is bonded to connector adapter 130 which forms a part of adapter assembly 108. Chamber 130a houses a conventional umbrella check valve 132 that controls fluid flow toward and away from the fluid dispenser 30. As container subassembly, 106 is pushed inwardly, fluid under pressure will then flow past umbrella check valve 132 into a passageway 134 formed in connector 130 and then into the internal passageway of a piercing cannuia 136 that is securely connected to connector adapter 130. As before, the fluid contained within chamber 110c can take various forms such as those previously described.

When the reservoir fill assembly 102 of this latest form of the invention is mated with closure cap 40 of the fluid dispenser in the manner shown in Figure 11, cannuia 136 will pierce pierceable septum 78 which is carried by closure cap 40 thereby permitting fluid to flow into reservoir 34e of the fluid dispenser via passageway 79 which communicates with reservoir inlet 35.

Prior to use, the ends of the assemblage shown in figures 12 and 14 are substantially sealed by previously bonded, sterile barrier members 137 and 139. Similarly, sleeve 120 is sealed by a barrier member 141 and the closure cap 40 of the fluid dispenser is closed by a barrier member 91 (figure 10).

Referring to figures 11, 14, 14A and 14B, it is to be noted that sleeve 120 is provided with a plurality of longitudinally spaced apart locking teeth 120t which are sloped so as to slide under an inwardly extending, resiliently deformable locking tab 125 that forms a part of clip 125a that is connected to housing 124 in the manner shown in figure 14A. See also figure 14B which shows the radius R-1 of clip 125a to be greater than the radius R-2 of housing 124 so that clip 125a will snap into a locking position with housing 124 in the manner shown in figure 14A. Because of the shape of teeth 120t they will engage tab 125 in a manner to prevent removal of sleeve 120 after it has been inserted into sleeve 124 thereby preventing reuse of the fill assembly (see also figure 11).

Turning particularly to figures 17 and 19, the novel field filling of the container sub- assembly 106 is there illustrated, To enable coupling of, a fluid containing syringe assembly "S" (figure 19) with the container subassembly 106, end 120a of sleeve 120 is closed by a hingeably connected closure member 140. As best seen in figure 19, closure member 140 includes a generally cylindrically shaped body portion 140a that is sealably received within a chamber 142 defined by end portion 120a Of sleeve 120. Body portion 140a is connected to sleeve 120 by a living hinge 143 so that the closure member can be moved from the closed position shown in figure 17 to'the open position shown in figure 19. When the closure member is in the open position, the cannuia S-l of syringe "S" can be placed in communication with reservoir 110c by piercing septum 112 in the manner shown in figure 19 so that the reservoir can be filled with fluid. As the reservoir fills, plunger assembly 116 will be moved from the position shown in figure 17 to the intermediate position shown in figure 19 and then into the position shown in figure 11. In this position, by relative rotation of the parts, plunger 116 can be threadably interconnected with head 126b of pusher member 126. Gases displaced by the relative movement of the plunger assembly will pass through vent ports 120c in tear away cap llOd and vent patch 114.

With the reservoir fill assembly thus charged with the fluid-to be used in filling reservoir 34e of dispenser 30, the fill assembly 104 can be interconnected with dispenser 30 in the manner shown in figure 11, To interconnect the reservoir fill assembly with the fluid dispenser, the circumferentially spaced bayonet locking ears 92 of adapter 130 are inserted within the circumferentially spaced slots 94 formed in dispensing head assembly 38 (figures

10 and 11). Relative rotation of the reservoir fill assembly and the fluid dispenser component will then effect a sterile interconnection between the reservoir fill assembly and the fluid dispenser. As the reservoir fill assembly is thus aseptically mated with the fluid dispenser, cannuia 136 of the reservoir assembly will pierce pierceable septum 78 which is mounted within connector adapter 130. This done, an inward pressure exerted on closure member 140 will cause sleeve 120 to move forwardly of annular space 123. As sleeve 120 and container subassembly 106 are urged inwardly, the fluid contained within reservoir 110c will flow into cannuia 128, past check valve 132, into passageway 134, into cannuia 136, into passageway 79 and thence into reservoir 34e. Curved finger grips 147 are provided on housing 124 to assist in urging sleeve 120 inwardly of housing 124.

As the fluid under pressure flows into chamber 34e of the dispensing apparatus, the stored energy means, or resilient member 50, will be compressed by stopper member 51 causing internal stresses to be built up within the member, which stresses tend to return the member along with stopper 51 toward the first configuration. With reservoir 34e thusly filled, protective sheath 95a, which covers infusion cannuia 97 (figures 3 or 11) can be broken away and the infusion cannuia appropriately inserted into the infusion site to commence the controlled delivery to the patient of the beneficial agent contained within reservoir 34e via the flow control means of the invention. Connector wings 99 are provided on needle housing body 95 so that the device can be connected to the patient's body by means of an adhesive provided on the lower surfaces of wings 99.

Referring now to figures 20 through 26, still another form of the fluid delivery apparatus of the invention is there shown and generally designated by the numeral 150. This apparatus is also similar to the apparatus shown in figures 1 through 10 and like numerals are used in figures 20 through 26 to identify like components. In this latest embodiment of the invention, the fluid dispenser is once again identical to that previously described. However, a somewhat different fill assembly is here provided, This alternate fill assembly, which is generally designated by the numeral 152, is interconnected with the fluid dispenser by a dispenser connector of the character previously described. As before, a connector adapter 130, is provided and includes circumferentially spaced locking ears 92 which are lockably receivable within slots 94 of dispensing head assembly 38. However, unlike the previously described fill assemblies, this latest fill assembly comprises a housing 154 which accepts a vial assembly 156 that uniquely contains a lyophilized drug 157 and a reconstituting fluid 159. Reconstituting fluid 159 is initially separated from the lyophilized drug by a movable barrier stopper 160 (figures 21 and 26). Lyophilized drug 157 can, by way of example, comprise anti-infectives, anticoagulants, chemotherapeutic agents and many others to preserve the therapeutic value of the agent. o Vial assembly 156 is telescopically receivable within the open end 162a of an adapter sleeve 162 that is, in turn, receivable within an annular shaped opening 164 formed within

/ / housing 15 As shown in figure 22, sleeve 162 includes a pusher member 162b that en- s gages a/plunger 166 that sealably closes one end of a vial 174 that forms a part of vial assembly 156. During the mixing step pusher member 162b functions to push plunger 166 forwardly of vial 174 to cause mixing of the fluid 159 with the lyophilized drug 157. This novel mixing step will be described more fully in the paragraphs which follow.

Referring particularly to figures 21, 22, and 26, vial 174 as presented to adapter sleeve 162, it is sealed at one end by the previously identified plunger 166 and is sealed at the other end by a pierceable septum 176 (figure 26). Formed intermediate the ends of vial 174, which is readily commercially available, is a raised outer wall portion 174a which permits fluid 159 to bypass barrier 160 as the barrier member is urged inwardly of the container by pressure exerted thereon by the fluid 159. Fluid 159 exerts pressure on barrier member 160 as a result of pusher member 162b exerting inward pressure on plunger 166. Pressure on plunger 166 is, in turn, caused by the inward movement of plunger 166 due to the urging of pusher member 162b as sleeve 162 is pushed inwardly of annular space 164.

Prior to the mixing step, assembly 162 is mated with assembly 154 in a manner shown in figure 22. During this mating step a hollow cannuia 155 provided on housing 154 will pierce septum 176. With the components in this position, a fluid communication path exists between the interior of via! 174 and the fluid dispenser 30. Accordingly, an inward pressure is exerted on adaptive sleeve 162, will urge barrier member 160 forwardly to a position that will permit fluid 159 to flow past the barrier member via wall portion 174a. As the fluid flows into the chamber containing the lyophilized drug 157, the drug will be recon- stituted to form a reconstituted drug or dispensing mixture. As plunger 160 continues to move forwardly, this dispensing mixture will flow into hollow cannuia 155 and then into chamber 70a that houses the previously identified umbrella check valve 72. The dispensing fluid will then flow past check valve 72 into passageway 74 and finally into hollow cannuia 76 (figure 22).

Upon mating the fill assembly of this latest form of the invention with the fluid dispenser in the manner previously described, cannuia 76 will pierce septum 78 permitting the reconstituted drug to flow into chamber 34e via inlet 35. Prior to the interconnection of the various components of the device, cap 40 is substantially sealed by a peel cover 91. Similarly, housing 154 is sealably closed by peel covers 181 and 183 while vial assembly 156 is closed by a peel cover 185 and open end 162a of sleeve 162 is closed by a peel cover 187 (figure 20).

To interconnect the fill assembly with the fluid delivery apparatus, ears 92 of assemblage 154 are inserted into slots 94 of cap 40 of the fluid dispenser. Relative rotation between assemblage 154 and cap 40 will then bring ears 92 into locking engagement with cap 40 thereby securely connecting the fill^" assembly with the. dispenser unit, Filling of reservoir 34e is then accomplished by pushing sleeve 162 inwardly into annular space 164. In this ... regard, it is to be noted thatsleeve.162. is. provided with a plurality of longitudinally spaced-,_,, apart locking teeth 162t which are sloped so as to slide under an inwardly extending, resil- iently deformable locking tab 191 that is connected to housing 154 in the manner best seen in figure 22. However, because of the shape of teeth 162t, they will engage tab 191 in a manner to prevent removal of sleeve 162 after it has been inserted into housing 154 thereby preventing reuse of the fill assembly.

As the dispensing fluid flows under pressure into chamber 34e of the dispensing ap- partus, the stored energy means, or member 50, will be compressed by stopper member 51 causing internal stresses to be built up within the member, which stresses tend to return the member along with stopper 51 toward the first configuration. With reservoir 34e thusly filled, protective sheath 95a, which covers infusion cannuia 97 (figure 22) can be broken away and the infusion cannuia appropriately inserted into the appropriate infusion site to commence the controlled delivery to the patient of the dispensing fluid contained within res- ervoir 34e via the flow control means of the invention. Once again, connector wings 99 are provided on needle housing body 95 which is connected to dispensing head 38 so that the device can be connected to the patient's body by means of an adhesive provided on the lower surfaces of wings 99.

Referring to figures 27, 28, and 29 still another embodiment of the dispensing apparatus of the invention is there shown. This form of the invention is similar to that shown in figure 20 and like numerals are used to identify like components. The principal difference between the embodiment shown in figure 20 and that shown in figures 27, 28, and 29 resides in the differently configured connector adapter, which is here designated by the numeral 193. Unlike connector adapter 130, connector adapter 193 is provided with three circumferentially spaced ears 195 (figure 28) which ears are lockably receivable within three circumferentially spaced slots 197 (figure 29) formed in dispensing head assembly 199. As in the earlier described embodiments of the invention, after the ears 195 are received within mating slots 197, relative rotation of the, reservoir fill assembly and the fluid dispensing assembly will effect a sterile Interconnection of the components. It is to be appreciated that only an appropriately configured fill assembly can be mated with the dispensing assembly . thereby effectively avoiding accidental filling of the dispensing assembly with the wrong _f medicinal agent. For example; with the construction .shown' in figure 29, a fill assembly 56 , of the character shown in figure 1 having four locking ears could not be mated with the connector adapter 199.

In the form of the invention shown in figures 16 through 29, housing 34 as well as container subassembly 106 are constructed of a plastic material such as, for example, a polycarbonate, an acrylic polystyrene, polyvinylchloride, polyethylene, polyester, PMMA, polysulfone, polyurethane, polyamide, polyvinylalcohol, polypropylene. With this construction, the interior surfaces of housing 34 and container subassembly 106 as well as the fluid flow passageways of the dispenser can be surface modified or coated with various materials to form thin conformable, protective, interfacial barriers "B" for biological compatibility or to promote wetlubricity or wettability.

These surface treatments can include hydrophilic agents that offer a wide range of wettability characteristics which can be tailored to meet the required surface wetting, prim- ing, reduction of gas bubble adhesion, and other flow performance characteristics. Other forms of these coatings can also reduce the absorption and denaturation of other biomateri- als including proteins. Alternatively, modified proteins, peptides, carbohydrates and synthetic polymers can also be covalently bonded to surfaces to generate ultrathin coatings or crosslinked to generate other three dimensional intermediate polymer matrices to either inhibit other biochemical responses or for immobilization of related biomaterials. These coatings and surface modification treatments are readily available from multiple sources and well known to those skilled in the art.

Having now described the invention in detail in accordance with the requirements of the patent statutes, those skilled in this art will have no difficulty in making changes and modifications in the individual parts or their relative assembly in order to meet specific requirement or conditions. Such changes and modifications may be made without departing from the scope and spirit of the invention, as set forth in the following claims.

Claims

I CLAIM

1. A dispensing apparatus for dispensing fluid comprising :

(a) a fluid dispenser comprising :

(i) a housing assembly including a housing having a fluid reservoir, said reservoir having a fluid inlet for filling said reservoir with fluid and a fluid outlet for permitting fluid flow from said fluid reservoir, said housing assembly having a dispenser connector; and

(ii) stored energy means for acting upon the fluid contained within said reservoir to cause the fluid to controllably flow through said outlet, said stored energy means comprising a compressively deformable, elastomeric member carried within said reservoir, said elastomeric member being expandable to cause fluid flow from said reservoir toward said fluid outlet; and

(b) a reservoir fill assembly connected to said fluid dispenser for filling said reservoir with the fluid to be dispensed, said reservoir fill assembly comprising:

(i) a hollow housing;

(ii) a connector adapter connected to said housing for interconnecting said housing with said dispenser connector;

(iii) a container assembly telescopically receivable within said housing, said container assembly including a container and plunger disposed within said container; and

(iv) pusher means operably associated with said housing for moving said plunger within said container.

2. An apparatus as defined in claim 1 in which said plunger is connected to said pusher means.

3. An apparatus as defined in claim 1 in which said pusher means comprises a pusher member having a threaded end and in which said plunger is threadably connected to said threaded end of said pusher member.

4. An apparatus as defined in claim 1 in which said connector adapter includes circumferentially spaced locking ears and in which said dispenser connector is provided with circumferentially spaced slots for receiving said locking ears.

5. An apparatus as defined in claim 1 in which said reservoir fill assembly further comprises a piercing cannuia for piercing said plunger upon connection of said reservoir fill assembly with said fluid dispenser.

6. The apparatus as defined in claim 1 in which said elastomeric member comprises a flexible, resilient, polymeric member.

7. The apparatus as defined in claim 1 in which said elastomeric member comprises a cellular mass.

8. The apparatus as defined in claim 1 in which said container assembly further includes a pierceable septum carried by said container and in which said reservoir fill assembly further includes a sleeve telescopically receivable within said housing, said sleeve having a first end for receiving said container and a second end closed by a closure member hingedly connected to said second end of said sleeve.

9. The apparatus as defined in claim 1 in which said container of said container assembly includes a chamber containing a lophilized.drug and a first chamber containing a reconstituting fluid to be intermixed with said lyophilized drug.

10. The apparatus as^' defined in.claim 1 in which said fluid dispenser further includes an infusion cannuia in communication with said fluid outlet of said reservoir.

11. The apparatus as defined in claim 10 in which said fluid dispenser further includes flow control means disposed between said reservoir and said reservoir fill assembly for controlling fluid flow from said reservoir fill assembly toward said reservoir.

12. The apparatus as defined in claim 10 in which said fluid dispenser further includes flow control means disposed between said fluid reservoir and said infusion cannuia for controlling the rate of the fluid flow from said reservoir toward said infusion cannuia.

13. The apparatus as defined in claim 12 in which said flow control means further comprises filter means for filtering particulate matter from fluid flowing from said reservoir.

14. The apparatus as defined In claim 12 in which said flow control means comprises a porous frit disposed between said reservoir and said infusion cannuia.

15. The apparatus as defined in claim 12 in which said flow control means com- prises a capillary bore disposed between said reservoir and said infusion cannuia for controlling the rate of fluid flow toward said infusion cannuia.

16. The apparatus as defined in claim 15 further including a delivery line disposed between said reservoir and said infusion cannuia and in which said capillary bore is disposed within said delivery line.

17. The apparatus as defined in claim 16 in which said flow control means further comprises a porous rate control wafer element and a filter element disposed within said housing.

18. A dispensing apparatus for dispensing fluid comprising :

(a) a fluid dispenser comprising :

(i) a housing assembly including a housing having a fluid reservoir, said reservoir having a fluid inlet for filling said reservoir with fluid and a fluid outlet for permitting fluid flow from said fluid reservoir, said housing assembly having^' a- dispenser ^"•connector;^*. : ^• " '

(ii) a pierceable septum carried by said dispenser connector; and (iii) stored energy means for acting upon the fluid contained within said reservoir to cause the fluid to controllably flow through said outlet, said stored energy.. means, comprising a compressively deformable, elastomeric member carried within said reservoir, said elastomeric member being expandable to cause fluid flow from said reservoir toward said fluid outlet; and

(b) a reservoir fill assembly connected to said fluid dispenser for filling said reservoir with the fluid to be dispensed, said reservoir fill assembly comprising :

(i) a hollow housing;

(iii) a hollow cannuia carried by said connector adapter for piercing said pierceable septum of said fluid dispenser;

(iv) a container assembly telescopically receivable within said housing, said container assembly including a container and plunger disposed within said container; and

(v) pusher means operably associated with said housing for moving said plunger within said container.

19. An apparatus as defined in claim 18 in which one of said connector adapter and said dispenser connector includes circumferentially spaced locking ears and in which the other of said connector adapter and said dispenser connector is provided with circumferentially spaced slots for receiving said locking ears.

20. The apparatus as defined in claim 18 in which said elastomeric member comprises a flexible, resilient, polymeric member.

21. The apparatus as defined in claim 18 in which said elastomeric member comprises a cellular mass.

22. The apparatus as defined in claim 18 in which said container assembly further includes a pierceable septum carried by said container and" in which said reservoir fill assembly further includes a sleeve telescopically receivable within said housing, said sleeve having a first open end for receiving said container.

23. The apparatus as defined in claim 22 in which said container of said container assembly includes a chamber containing a lyophilized drug and a chamber containing a reconstituting fluid to be intermixed with said lyophilized drug.

24. A dispensing apparatus for dispensing fluid comprising : (a) a fluid dispenser comprising :

(i) a housing assembly including a housing having a fluid reservoir, said reservoir having a fluid inlet for filling said reservoir with fluid and a fluid outlet for permitting fluid flow from said fluid reservoir, said housing assembly having a dispenser connector;

(ii) a pierceable septum carried by said dispenser connector; and (iii) stored energy means for acting upon the fluid contained within said reservoir to cause the fluid to controllably flow through said outlet, said stored energy means comprising a compressively deformable, elastomeric member carried within said reservoir, said elastomeric member being expandable to cause fluid flow from said reservoir toward said fluid outlet; and

(iv) delivery means, including a fluid delivery line in communication with said fluid outlet of said reservoir for delivering the fluid from said dispensing apparatus; and

(i) a hollow housing;

(v) pusher means operably associated with said housing for moving said plunger within said- container.

25. An apparatus as defined in claim 24 in which one of said connector adapter and said dispenser connector includes three circumferentially spaced locking ears and in which the other of said connector adapter and dispenser connector is provided with three circumferentially spaced slots for receiving said locking ears.

26. The apparatus as defined in claim 24 in which said delivery means further includes bolus means for introducing a bolus dose into said fluid delivery line.

27. The apparatus as defined in claim 24 in which said fluid dispenser further includes flow control means disposed between said reservoir and said reservoir fill assembly for controlling fluid flow from said reservoir fill assembly toward said reservoir.

28. The apparatus as defined in claim 24 in which said delivery means includes flow rate control means comprising a small bore capillary disposed within said delivery line.

29. The apparatus as defined in claim 24 in which said reservoir fill assembly in- eludes flow control means for controlling fluid flow from said reservoir fill assembly toward said fluid dispenser.

30. The apparatus as defined in claim 24 in which said container assembly of said container assembly includes a chamber containing a lyophilized drug and further includes a chamber containing a reconstituting fluid to be intermixed with said lyophilized drug.

31. The apparatus as defined in claim 30 in which said container assembly further includes a barrier member disposed between said chamber containing said lyophilized drug and said chamber containing said reconstituting fluid.

32. The apparatus as defined in claim 31 in which said container of said container assembly includes an upraised wall portion which permits fluid to flow past said barrier member in a direction toward said lyophilized drug.

33. A dispensing apparatus for dispensing fluid comprising :

(a) a fluid dispenser comprising :

(ii) a pierceable septum carried by said dispenser connector; and

(iii) stored energy means for acting upon the fluid contained within said reservoir to cause the fluid to controllably flow through said outlet, said stored energy means comprising a compressively deformable, elastomeric member carried within said reservoir, said elastomeric member being expandable to cause fluid flow from said reservoir toward said fluid outlet; and

(b) a reservoir fill assembly connected to said fluid dispenser for filling said reservoir with the fluid to be dispensed, said reservoir fill assembly comprising : (i) a hollow housing having interior walls provided with a protective barrier;

(iv) a container assembly telescopically receivable within said housing, said container assembly including a container having interior walls provided with a protective barrier and plunger disposed within said container; and

34. The apparatus as defined in claim 33 in which said fluid dispenser further includes flow control means disposed between said reservoir and said reservoir fill assembly for controlling fluid flow from said reservoir fill assembly toward said reservoir.

35. The apparatus as defined'.in claim 33 in which reservoir fill assembly includes flow control means for controlling fluid flow from said reservoir fill assembly toward said fluid dispenser.

36. The apparatus as defined in claim 33 in which said delivery means includes flow rate control means comprising a microbore capillary disposed within said delivery line.

37. The apparatus as defined in claim 33 in which said protective barrier provides wetlubricity.

38. The apparatus as defined in claim 33 in which said protective barrier provides wettability.

39. The apparatus as defined in claim 33 in which said protective barrier provides biological compatibility.

40. The apparatus as defined in claim 33 in which said protective barrier provides an intermediate polymer matrix for immobilization and biomaterials.

41. The apparatus as defined in claim 33 in which said protective barrier comprises a hydrophilic agent.