CN103429287A

CN103429287A - Aseptic cartridge and dispenser arrangement

Info

Publication number: CN103429287A
Application number: CN2011800669000A
Authority: CN
Inventors: A.吉诺萨
Original assignee: Aktivpak Inc
Current assignee: Aktivpak Inc
Priority date: 2011-01-17
Filing date: 2011-12-07
Publication date: 2013-12-04
Also published as: JP6325608B2; JP5969497B2; JP2016195800A; JP2014501124A

Abstract

A cartridge for use with a beneficial agent delivery device having a fillable reservoir. The cartridge includes a reconstitution, unit dose package having first and second compartments, and a fitment. The first compartment contains at least a first constintuent of the beneficial agent. The second compartment contains at least a second constituent of the beneficial agent. The fitment is disposed on the package for interfacing the package to the fillable reservoir.

Description

Aseptic box and dispenser device

Technical field

The present invention preferably, but is not limited to, and relates generally to the disposable cassette used together with drug delivery device, and more specifically relates to the aseptic mixing cassette for drug delivery device.

Background technology

Medicine, especially injectable medicine needs sterilely (sterile) to be stored in aseptic (aseptic) commercial packing until while using.Some medicine storages are at pre-filled single dose dispensation apparatus (dispensing device), such as pre-filled syringe, for example, from Vetter(Ravensburg, Germany) pre-filled syringe.Yet most of injectable medicine storages, in aseptic packing, and are transported to dispensation apparatus (that is, drug delivery device) before use soon.The term dispensation apparatus includes but not limited to hypodermic syringe, microneedle syringe, micropump, automatic injector, ejector filler, external dispenser, Intradermal delivery apparatus, attaches pump (patch pump), ear dispenser, oral dispenser, eye dropper, automatic injector, transfusion device, or the drug delivery device of any other type.

Severally for the aseptic packing of storing injectable medicine, can buy from market.May most of common aseptic packings for injectable product be vials.Some medicine storages, in independent parts, only mix before use.Usually, doing like this is stability in order to improve medicine or for pot-life of prolong drug.In one example, medicine is vaccine, and it is kept in a bottle dryly to extend the vaccine heat stability; And the pairing bottle is stored diluent, and it is dispensed to vaccine via syringe and entry needle before injection.In another example, medicine is vaccine, and one of them bottle is stored the antigen of manufacturing by formula, and second bottle stored adjuvant.

Yet there are some shortcomings in prior art: (a) for the many injectable drugs such as vaccine, these are packaged in many time is expensive and unpractiaca economically; (b) wherein, need to be mixed each component of medicine, and this processing is complicated and is easy to make a mistake; And (c) by medicine or its component from a container transport to another container or to be transported to dispensation apparatus be the completing on the spot of non-sterile property, and contaminated risk is easily arranged.

United States Patent (USP) the 7th, disclose a kind of of some business for mixing injectable medicament and patent external member for 879, No. 018.Here, again, the restriction of disclosure be to the dependence of bottle with to such glass, be cost and the complexity that primary tank is relevant.

Some commercial products and patent disclose the flexible package of being made by thin film or paper tinsel, and wherein product can the aseptic mode be stored until while using.Some in these products and patent further disclose the port that makes up a prescription communicated with the product made up a prescription in packing.In some cases, before using, between described port and product, exist destructible obstruct to strengthen the integrity of packing.In some cases, these flexible packages comprise at least two product compartment, and it can merge before use, to allow material from different compartments to mix and to form assignable product.Sometimes these packings are called sack (pouche) or pouch (sachet).A shortcoming of bag type package is that it is quite challenging the whole content of packing being extruded to (express).This is the dimension scale due to these packings, and wherein length and width significantly are greater than the vertical protuberance (perpendicular protrusion) on its plane usually.This ratio is the inherent limitations that forms the mode of sack/pouch.Sack and pouch are formed by one or more thin film or paper tinsel (being referred to as " thin slice (web) "), and these one or more thin film or paper tinsel at its edge seal together, form one or more containers.This sack is during container forms or be filled afterwards, then sealed to keep product to be wired up by aseptic.

When directly being operated with hands, a restriction of the packing that these are relatively shallow is that, when making up a prescription, operator's thumb makes the wall contact that two of packing are relative, the termination of making up a prescription at the contact point place very rapidly.In order from packing, to extrude extra product, usually must carry out complicated peristaltic action or folding to packing.In some configurations, with pressing plate, press flexible package, so that content is discharged.In these are arranged, operated clamp with press product compartment therefore to make the pressure that generation is larger than small area of contact be favourable.Therefore, the compartment area coverage less of generating content thing and sealing area and the ratio between surperficial Package size is less perpendicular to this flexibility packing of making up a prescription is favourable.

In some applications, the medicine that can send needed at least two kinds of materials are thoroughly mixed before injection.In one example, need simple method in the high heldwater (W/O) of using while putting in being formulated in oil.At present, Emulsion is that reciprocally oil and the water of hybrid separation are manually prepared by the threeway stopcock via connecting two syringes or narrow pipe.The method is a bit consuming time and be often unsettled.Developed the adapter that there is perforated membrane in syringe inside, so that more effective Emulsion to be provided, but the cost that will pay be need to be stronger thrust, especially when in order to shorten the preparation time, reducing aperture.In addition, the assembly and disassembly step that number increases has increased operation mistake and has polluted the risk that can send medicament.

Summary of the invention

At least some aspects of the present invention are by for example providing low-cost, simply and easily with box, overcome shortcoming and the restriction of prior art.In some configuration, box allows sterilely to mix and fill dispenser, especially drug delivery infusion appliance.

In configurations more of the present invention, packing is made by least one sheeting, and the first wall of wherein said sheeting and the second wall are linked together along the boundary line of compartment.In some configurations, sheeting is pre-formed into and makes the relatively large volume of realizing compartment by the relatively little sealing area of coverage (footprint).This preformed packing can reduce the overall dimensions of packing, and improves storage and conevying efficiency.

According to a kind of configuration of the present invention, the box with thin flexible wall packing comprises at least the first component compartment and has the adnexa that box is connected to the dispenser fill port.This adnexa is attached to packing with fluid sealing mode.This adnexa can be in the following manner a kind of dispenser fill port that is attached to, include but not limited to the screw thread on Rule adapter, luer lock connection, interference fit adapter, snap-on adapter, buckle or cap.

In some configurations, at least one chamber preform is at least one of thin slice wall of packing, and this chamber provides the part of at least one product compartment of described packing.For the product of the same volume of storage, the sealing area (area of coverage (footprint)) of this configuration permission compartment is smaller with the compartment size (protuberance of compartment) perpendicular to sealing area.Have the required compartment area of coverage of the pouch/bag packaging of similar products volume with utilization and compare, this configuration also allows the area of coverage of compartment less.The formation of thin slice can be by applicable particular sheet characteristic as known in the art mode (comprise, for example hot forming, cold forming, preheating shaping, plunger are auxiliary, pressure forming, vacuum forming and above combination) in a kind of the execution.

In some configurations, this packing be utilize form as known in the art (comprise, for example, bubble-cap, sack, pouch, blow-molded container or extrude container) in a kind ofly by thin-wall configuration, become.In some configurations, this packing can have more than a compartment, but for storing the many kinds of substance that need to be mixed to form allocated product before being delivered to object.This compartment can be by weak hermetic separation, can with the threshold pressure that surpasses at least one material, make a little less than this seal to break by least one in the compression compartment, and this will make weak sealing remove (for example, ftracture or peel off) and allow the material mixing.This packing further comprises the interface for dispenser.

In some configurations, product is transferred to dispensation apparatus from box.In some configurations, in dispensation apparatus, box is replaced.In certain embodiments, in the fabrication stage, with sterile manner, box is connected to dispenser, so user does not need by the step of box and dispenser combination.This configuration has reduced the user mistake or device maybe can be sent the probability of the pollution of product because its avoided filling in dispenser/load process before or during to the exposure of non-sterilized environment.In the another kind configuration, box and dispensation apparatus (being syringe, infusion appliance etc.) are stored separately, until use constantly.Need to be in controlled environment at medicine, such as in the situation that store in controlled temperature cold preservation and transmission and in the situation that packaging efficiency is very important, this layout may be favourable.For the mode of homology and delivery apparatus not of logic and customer flexibility select to(for) enhancing, this layout may be also favourable.

In some configurations, dispensation apparatus can be infusion appliance.The term infusion appliance can refer to different allocated product, comprises micro-infusion pump or reservoir, such as, such as lip pencil infusion appliance, reservoir assembly, syringe, needleless infusion appliance, drug delivery device generally speaking, adhering device etc.More extensive, box of the present invention, applicable to dispensation apparatus, comprises for example oral or droplet ear device, spraying or foam dispenser, external applicator and respiratory organ for eye.

In the another kind configuration, static mixer is arranged in the joint between box device and drug delivery device, to strengthen, can send the mixing of product ground and uniformity.United States Patent (USP) the 4th, instructed the example of static mixer in 538, No. 920, and the full content of this patent is incorporated herein as a reference.In some configurations, static mixer is configured to the channel pattern formed between the wall of flexible wall, and this channel pattern forms by the appointed area of welding and preform wall.This static mixer can be only narrow nozzle, or is contained in the porous member in the flow channel between box and delivery apparatus.In a kind of configuration, static mixer is arranged in the box port.In a kind of configuration, box comprises more than a compartment, should hold different material more than a compartment, and merge before content is transferred to delivery apparatus, and the mixing of static mixer enhancing substance when material is transferred to delivery apparatus.

In some configurations, mixture can shift back and forth between box and delivery apparatus, further material is mixed.In some configurations, at least one material is stored in box, and at least one material is stored in delivery apparatus, and material shifts that back and forth material is mixed between box and delivery apparatus.In a kind of configuration, this box comprises at least the first and second compartments, and at least one static mixer is arranged between the first compartment and the second compartment.Can strengthen mixing by material/mixture is transferred to other compartments from a compartment.At least one compressive plate or compressive plate device can operate together with box, to contribute to cross the static mixer transfer of material.

Content of the present invention also includes the apparatus and method that help manufacture efficiently and fill box.In a kind of configuration, the compartment of packing is filled with fluid.This compartment is formed sealing, stays the appointment open access that leads to port, by this port, introduces fluid and Exhaust Gas.Can comprise the independent passage of discharging for gas.Passage can be configured so that the wall slip of the fluid of entry port along packing, has therefore avoided injection, and has minimized foaming or bubble formation, therefore allows the raising fill rate.

In another kind configuration, liquid substance was frozen before filling, and packed in packing with solid form.Pack temperature on every side and controlled to the heat transfer of packing during filling processing, making freezing liquid basically remain solid until compartment is sealed.Before filling or during, freezing liquid substance dosage can be examined with this form.This filling device and method have improved filling speed and material checking ability.In a kind of configuration, the dried powder material must be filled in the box compartment.In order to contribute to correct powder filler, this powder, and is filled into this form in the compartment of packing to form the tablet of loose conglomeration by mild compression.This tablet can be in being filled into box before or during be examined.In a kind of configuration, in tablet is sealed to compartment after, therefore with the disaggregation tablet, improved the substance dissolves with mixing diluents the time from the peripheral operation compartment.This peripheral operation may be, but not limited to,, with lower at least one: the compression compartment, comprise vibration such as supersonic vibration, radio frequency vibration, audio frequency vibration etc., to compartment apply mechanical shock and be exposed to high temperature or low temperature in.

The invention further relates to by comprising that the peelable opaque parietal layer of high-barrier strengthens the configuration of the barrier properties of packing.Peelable high-obstruction can comprise the aluminium lamination tabletting, and it provides light-occlusive and has approached absolute humidity and the beneficial effect of oxygen obstruction.For the content of visual inspection box before use, peel off high-obstruction from least a portion of packing, expose the wall of substantial transparent.In a kind of configuration, strippable coating is the integral layer of manufacturing the sheeting of packing.In the another kind configuration, during the box manufacture is processed, strippable coating is applied to transparent wall.In a kind of configuration, strippable coating is smooth.In the another kind configuration, strippable coating is pre-formed into the material of its protection of adaptation or the form of compartment.In a kind of configuration, strippable coating comprises the bonding coat of the registration (registered) of the seal perimeter that optionally is applied to strippable coating.In a kind of configuration, the form that box is flexible and transparent wall pipe, and strippable coating is arranged to rolling tube.

Another aspect of the present invention relates to for having the box of the useful drug delivery device that can fill reservoir.This box comprises reconstruct formula unit dose packaging and the adnexa with first and second compartments.At least the first component that this first compartment comprises described useful medicament.At least second component that this second compartment comprises described useful medicament.This adnexa is arranged on described packing, for by described packing with can fill reservoir and join.

Another aspect of the present invention relates to a kind of for having the aseptic box of the useful drug delivery device that can fill reservoir.This box comprises packing and the adnexa with at least the first compartment.At least one component that the first compartment comprises useful medicament, described packing is limited by preformed flexible wall at least in part.Adnexa is arranged on described packing, for described packing is filled to reservoir joins and fluid is communicated with described.

Another aspect of the present invention relates to a kind of for having the box of the useful drug delivery device that can fill reservoir.This box comprises backing and package component.This package component comprises at least the first compartment and adnexa.At least one component that this first compartment comprises useful medicament, and by flexible wall, limited at least in part.Adnexa is arranged on described packing, for by described packing with can fill that reservoir joins and fluid is communicated with.

Another aspect of the present invention relates to a kind of for having the box of the useful drug delivery device that can fill reservoir.This box comprises packing, adnexa and the coupler with at least the first compartment.At least one component that the first compartment comprises useful medicament.Adnexa is arranged on the packaging.Coupler is connected to described adnexa, for described packing is filled to reservoir joins and fluid is communicated with described.

Further aspect relates to a kind of for having the box of the useful drug delivery device that can fill reservoir.This box comprises unit dose packaging, and it comprises all described useful medicament or its all components.This box comprises at least the first compartment of at least one component that comprises whole useful medicaments or described useful medicament, and wherein said the first compartment is limited by flexible wall at least in part.Described box also comprises the adnexa be arranged on described packing, and this adnexa is for being communicated with described packing with the described reservoir also fluid that joins of filling.

Further aspect relates to a kind of pre-filled cap, for sealing the administration part of the useful drug delivery device of the unit dose that comprises the monoblock type reservoir.This pre-filled cap comprises at least the first compartment of at least one component that comprises useful medicament, and for making described the first compartment and the partially communicating fluid passage of described administration.

Useful medicament unit dose dispenser according to the present invention comprises delivery apparatus and box.Delivery apparatus has the unit dose reservoir that can fill and fills with described at least one port that reservoir is communicated with.This box is aseptic is connected to described delivery apparatus, and comprises unit dose packaging.This unit dose packaging comprises at least the first compartment, adnexa and openable sealing.At least one component that the first compartment comprises described useful medicament, and described packing is limited by flexible wall at least in part.Adnexa and unit dose packaging link, and unit dose packaging and delivery apparatus are joined.Openable sealing is arranged between the first compartment and reservoir.

Another aspect of the present invention relates to a kind of for distributing the pre-filled syringe of useful medicament.This pre-filled syringe comprises piston component, comprises the sleeve of filling of administration part and pre-filled box.Pre-filled box comprises at least the first compartment of at least the first component that comprises described useful medicament, and is communicated to the flow channel of described sleeve for the content that makes described the first compartment.

Further aspect of the present invention relates to a kind of cap of the part of the administration for delivery apparatus, and described cap comprises fluid passage, is configured to and the partially communicating near-end of described administration, and far-end.

The method that relates to the pre-filled packing that is used to form useful medicament according to the embodiments of the invention method.The method comprises: the film with the first side and second side is provided, and this first side, with together with the second side is connected to, is formed on the border of at least the first component compartment between them; At least a portion along described border forms frangible; Form sealed-for-life, make at least some of the overlapping described frangible of described sealed-for-life, with generation, there is the overlapping part with the essentially identical sealing characteristics of described sealed-for-life; With described the first component compartment of filling.

Another kind of embodiment method according to the present invention relates to a kind of method that forms the pre-filled packing of useful medicament.The method comprises: the gas that is formed for described useful medicament is filled compartment; Formation has the filling compartment of fill port, and this fill port is filled compartment via the first salable channel and described gas and is communicated with; Have the emptying compartment of emptying port with formation, this port is filled compartment via the second salable channel and described gas and is communicated with.The method also comprises in a fluid tight manner the source of at least the first component of described useful medicament is connected with described fill port; Fill described gas via described filling channel from described source and fill compartment, simultaneously by described emptying port Exhaust Gas; With sealing the described first salable channel and described filling channel.

Further method according to the present invention relates to a kind of method of manufacturing the unit dose delivery apparatus of useful medicament, comprising: the delivery apparatus that receives assembling; Receive the box of pre-filled sterile sealing, it is by least the first component of pre-filled described useful medicament; With the box combination by described delivery apparatus and described sterile sealing.

Another kind of embodiment method relates to the unit dose packing with the useful medicament of liquid condition.The method comprises: in mould, the measurement unit dosage of freezing described useful medicament is to produce cryodose; Cryodose is put in half-done compartment; With the described compartment of sealing.

Another kind of exemplary method relates to the dosing packing by least the first component of the useful medicament of charge of flowable solids material forms.The method comprises: the dosage that measures described the first component; Compress the dosage of described metering, thereby be enough to form unitary body; Described unitary body is put in half-done packing; Seal described packing; With the wall by described packing, energy is directed to described monoblock type dosage, so that described monoblock type dosage is transformed into to microgranule.

Application of the present invention is not limited to drug delivery, and this drug delivery is in order to be provided in this for example.Instruction described here can be applicable to the distributor of other field, such as, such as glue distribution, chemicals distribution etc.Content of the present invention provides the difference that completes this operation configuration.

The accompanying drawing explanation

Fig. 1 a has illustrated the infusion appliance case assembly to scheming If, and it has the blister package be associated with its cap, and this infusion appliance case assembly can be used for different configurations;

Fig. 2 a and Fig. 2 b show injector assembly, and it has the blister package be associated with its cap, and this injector assembly can be used for different configurations;

Fig. 3 a and Fig. 3 b show pre-filled injector assembly, and it has the packing that is associated with its piston rod and extends axially out from it, and this pre-filled injector assembly can be used for different configurations;

Fig. 4 shows injector assembly, and it has the blister package that is associated with its bar and laterally extends from it, and this injector assembly can be used for different configurations;

Fig. 5 a and Fig. 5 b show the pre-filled box in spring driven needleless automatic injector;

Fig. 6 shows the pre-filled box in the needleless automatic injector driven at explosion type (pyrotechnically);

Fig. 7 shows the box of being made by the pipe of extrusion;

Fig. 8 shows the box that the pipe by extrusion in the needleless automatic injector of packing into is made;

Fig. 9 a shows and is arranged on the box that the pipe by extrusion on syringe is made;

Fig. 9 b shows and is arranged on syringe the box made of the pipe by extrusion that comprises peelable protection paillon foil;

Figure 10 a to Figure 10 e shows peelable part and wall extension box and the many operating procedures partly with shaping wall, and the peelable part of this shaping wall and wall extension partly form around the aseptic compartment that distributes port;

Figure 11 shows the box of the peelable part with smooth wall;

Figure 12 shows has the make up a prescription box of port of the flange that is attached to the box wall outside;

Figure 13 shows and the box be associated with the valve coupler that is communicated with syringe and syringe needle;

Figure 14 shows the box be associated with the far-end of syringe sleeve;

Figure 15 shows the semi-finished product box that is ready to carry out for useful medicament lyophilizing;

Figure 16 shows the box that comprises static mixer at its port that makes up a prescription, and two kinds of components that this static mixer contributes to be stored in box are mixed;

Figure 17 shows the first component and the system that is included in the second component in syringe that is included in box for mixing;

Figure 18 shows for mixing and is included in the first component of box and the system of second component;

Figure 19 shows the static mixer be formed in the bubble-cap flask;

Figure 20 a to Figure 20 e shows the method for the manufacture of box;

Figure 21 a to Figure 21 e shows the syringe that comprises static mixer, and wherein this static mixer mixes with the material in being included in box for the material that will be included in syringe;

Figure 22 a and Figure 22 b show the box be connected with the signature needle injection via adnexa;

Figure 23 a to Figure 23 f shows box that can be attached via coupler and gives as security needle injection; And

Figure 24 shows the another kind configuration of giving as security the pin coupler;

Figure 25 a to Figure 25 c shows the box that comprises coupler, and this coupler comprises injection needle;

Figure 26 shows and is suitable for having Intradermal (ID) injects the box of the syringe of pin jointer;

Figure 27 a and Figure 27 b show the box be associated with the ID syringe;

Figure 28 shows the another kind configuration of the box be associated with the ID syringe;

Figure 29 a and Figure 29 b show the another kind configuration of the box that comprises the ID needle apparatus;

Figure 30 shows the another kind configuration of the box that comprises the ID needle apparatus;

Figure 31 a and Figure 31 b show the box that comprises needle safety and forbid (disabling) feature;

Figure 32 shows the box with removable syringe needle;

Figure 33 a to Figure 33 e shows pre-filled injection device;

Figure 34 shows has backing that the pre-filled packing of box is protected and the box of wall.

Figure 25 d shows two sub-components of pre-filled cap;

Figure 25 e shows the decomposition view of the cap section of box;

In Fig. 3 a and Fig. 3 b, Reference numeral 39 illustrates adnexa;

In Fig. 4, Reference numeral 49 illustrates adnexa;

In Figure 15, the second compartment is that gas-tight seal becomes hollow, and can fill via filling device 152, as described in the drawings;

Figure 20 f illustrates frangible pattern 401;

Figure 20 g illustrates the sealed-for-life pattern 402 partially overlapped on frangible.

The specific embodiment

Figure la shows the configuration of infusion appliance 11 and box 10.The hatching of the cutaway view of Fig. 1 b is provided in figure.Figure lb shows the cutaway view of injector assembly 11 and box 10.Infusion appliance 11 comprises body 13 and the piston 14 of form of sleeve, and this piston 14 is arranged in described body and can moves between forward direction, dummy status and retraction, occupied state along the axis of body.Piston 14 further comprises O-ring packing 14 ', and the fluid-tight between described body and described piston is provided, and limits compartment in described piston the place ahead, for receiving the fluid medicament.Compartment is shown as the state in emptying (emptied), and wherein piston-advance is to position the most forward in body 13.Nozzle 17 in the body front portion provides port, for the fluid medicament is filled into to infusion appliance 11, and arrives object (subject) for the mode subcutaneous delivery that described medicament is injected to (needle-free jet injection) with needle-free jet.

Box 10 comprises the first thin-walled 18 ', and it is formed to provide two chambeies; Box 10 also comprises the second thin-walled 18 ", its sealing paste is by the first thin-walled 18 ', to limit the first sealed compartments 15 and the second sealed compartments 16.Adnexa (fitment) 12 is at the first wall 18 ' and the second wall 18 " between be attached to packing.Adnexa 12 is configured to engage with the front portion of infusion appliance body 13.The first frangible part 19 ' is separated the two between the first compartment 15 and the second compartment 16, and can be peeled off by the threshold force limited.The second frangible part 19 " between the second compartment 16 and adnexa 12, the two is separated, and the threshold value peeling force that can limit is peeled off.Thin-walled 18 ' and 18 " can be made by thin film or the paillon foil (being referred to as " thin slice (web) " or " sheeting ") of one type, this thin film or paillon foil comprise extrudes thin slice, blow out thin slice, the casting mold thin slice, composite wafer, laminated foil, coated sheet, comprise the thin slice such as the metal level of aluminium lamination, comprise the thin slice such as the metal oxide layer of aluminium oxide or silicon oxide, the thin slice that comprises high-obstruction (high barrier layer), this high-obstruction comprises cyclic olefin polymer (COP), cyclic olefine copolymer (COC), polytrifluorochloroethylene (PCTFE), vinyl alcohol (EVOH).The interior adhesive linkage of sheeting can be made by Surlyn A, ethylene vinyl acetate (EVA) or other material.

It may be favourable that adhesive linkage is attached to thin slice, this thin slice has controlled peeling force, make the appointed area of the circumferential seal around compartment there is the peeling force lower than other zone, therefore limited to the first wall 18 ' and the second wall 18 " between the zone that will ftracture while applying the threshold value peeling force of sealing area.A kind of such adhesive linkage is that trade mark is EZ

Ionomer blend (ionomer bland) (Bemis, Neenah, Wisconsin), it produces pealable seals under the seal temperature of 130 ℃, and produce permanent not peelable seal under the seal temperature of 170 ℃, therefore allow to process and control well sealing characteristics by carry out the welding of two stages with different temperatures.

At the first wall 18 ' and the second wall 18 " between realize that the another kind of approach of the sealing force pattern of expectation is that the internal layer of thin slice is made by least two bonding patterns of selectivity with bonding type of different peel strengths.Adnexa 12 can be made by alkene polymer, and its internal layer to thin slice has good cementation.In some configurations, adnexa is attached to the first wall 18 ' or the second wall 18 " in the outside of, and the through hole in thin slice communicates with content and the adnexa 12 of box 10.In this configuration, the adnexa material should be suitable for being attached to the cladding material of thin

slice.Box compartment

15,16 can hold different material.In one embodiment, the first compartment 15 holds diluent, and the second compartment 16 holds the useful medicament of dry form, and the content of two compartments need to mix to form assignable product medicament.In one embodiment, the first compartment 15 holds the diluent such as normal saline or water for injecting, and the second compartment holds the vaccine of dry powder form.

The content of the first compartment 15 and the second compartment 16 can be various ways, comprises liquid, gelinite, paste, slurry, solid, granule, spherolite, flowable powder, compressing powder, caking, lyophilizing piece or other forms known in the art.When the first compartment containing fluid material, can be by depressing the first compartment 15 and described content being exerted pressure, therefore the first frangible part 19 ' is applied power and falls sealing member and peel away, separate the first frangible part 19 ', generate and be connected compartment between compartment 15 and compartment 16, allow the contents mixed of two compartments.Can connect compartment and its content is exerted pressure by depressing, therefore produce for the second frangible part 19 " peeling force, make the second frangible part 19 " cracking.

Figure lc shows the box 10 be installed on infusion appliance 11.Adnexa 12 engages the front end of infusion appliance body 13, preferably in the adnexa zone, forms aseptic district band.The passage of adnexa 12 and infusion appliance nozzle 17 fluid communication.For parenteral subcutaneous medicament delivery applications, but to need to keep before use be sterilizing always for the All Ranges that touches delivered substance of device and the zone that will touch subject's body.In the configuration of figure lc, infusion appliance 11 engages for that zone maintenance sterilizing state with the aseptic of box 10.The sterilizing state of sleeve 13 inboards can be by the second sealing member in body 13 rear end, body 13 rear portions and piston 14 part local outer package or for the sterilizing outer package of whole device, maintain.Similarly solution will be applied to the layout of figure lb, and the additional aseptic lid that needs, for front area and the adnexa 12 of infusion appliance body 13.

The disinfection of adnexa 12 can be realized with protecgulum (lead) or the cap in protection port zone.The paper tinsel protecgulum can be heat-sealing to around port the periphery of vertical wall.In one embodiment, box 10 is stored in the sterilizing outer package.In certain embodiments, at least one in wherein said material is dried forms, in the sterilizing outer package, comprises that to migrate to dry compartment may be favourable to desiccant (such as dry capsule, ball or gel) to avoid dampness to pass

thin slice

18,18 ' wall.In one embodiment, dry matter can be attached to (this configuration is sometimes referred to as and removes film (scavenger film)) in thin slice.Box is packaged into infusion appliance and separates, can improve the controlled condition of drug products and store and transportation.In the configuration of figure lb, the sterilizing state of the front end of body 13 can be realized by different modes, comprises airtight cap, heat seal paper tinsel around nozzle 17 zones, and by whole infusion appliance is packaged in the sterilizing outer package.Therefore the layout of figure lc can advantageously reduce the required measure of sterilizing state that maintains product.

With reference now to Fig. 1 d,, show at frangible part (figure 19 ' and 19 in lc ") and ftractureed and the device that is connected compartment 16 ' figure lc afterwards of formation and the passage fluid connection of adnexa 12.

Figure le illustrates the configuration in Fig. 1 d the preceding, and wherein piston is retracted and caused fluid to flow to infusion appliance 11 from connecting compartment 16 ' from body 12.

Fig. 1 f shows the device in Fig. 1 e the preceding, wherein the state of piston 14 in retracting fully.Connect compartment 16 ' and be emptied completely, and its content is transferred to infusion appliance 12 fully.Box 11 is removed, and infusion appliance 12 is filled with now the product medicament that can send and is ready to use.Wherein, device is pre-sterilized, and the front portion of infusion appliance keeps sterilizing until the moment that adnexa 12 is removed.It can be favourable that this device is compared with commercially available device on market, and on market, in commercially available device, even before the infusion appliance filling step, the application surface of infusion appliance is exposed to non-sterilized environment, has therefore increased the pollution risk of object.

This device has shown the aseptic filling device of ejector filler box.In the further device of present disclosure, similarly device is provided to fill other boxes known in the art, dispenser or drug delivery device, comprise, for example, muscle, subcutaneous or Intradermal infusion appliance, with their box, applicator for external use and their box and reservoir, infusion pump, the micro-infusion pump, transfusion device, miniature apparatus infusionis, attach delivery apparatus, with their box and reservoir, the infusion vessel that comprises transfusion bag and infusion bottle, mouthful, eye or ear dispenser and their box and reservoir, sicker allotter and other dispenser, delivery apparatus, and for multi-form application and the applicator of purpose.

Fig. 2 shows the layout of pre-filled mixing cassette 10 and ordinary syringe 20.This figure provides the hatching of the cutaway view of Fig. 2 b.With reference to figure 2b, this box 10 comprises adnexa, and it ends at Rule (Luer) and locks recessed adapter, and its Luer lock male connector with syringe 20 couples mutually, forms fluid-tight and be connected between box 10 and syringe 20.Fluid can be identical by the infusion appliance with Fig. 1 mode transfer to syringe 20 from box 10.Injector tip will remain in gnotobasis always until while using, now box 10 will be removed.With the commercial product that injector tip or syringe needle end just were exposed to non-sterilizing territory and have therefore increased at filling step the risk that object pollutes in the past, compare, this layout may be favourable.In a layout, box in use between before keep separating with syringe always, they couple and combine by Rule in use.In order to maintain the sterilizing state of syringe 20 and box 10, can be adopted as layout likewise arrangement and the measure as described above of Fig. 1 b.

With reference to figure 3, another kind of configuration is provided, wherein the rear end of box and piston 31 links.Piston 31 comprises the fluid passage 32 along its axis, and it communicates with box port 9 and syringe bodies.At the front end of piston 31, plunger 34 is arranged so that, when piston 31 is drawn out, plunger 34 causes plunger 34 to move apart a little piston 31 with the frictional force of sleeve 33, therefore opens the fluid path 35(that the content that allows box transfers in sleeve 33 and sees arrow).Cap 37 maintains the sterilized space that syringe makes up a prescription around end 36.Fig. 3 b shows the device of Fig. 3 a after piston 31 has pulled into the position of pulling out fully and advanced.Box 10 has been emptied completely its content.Plunger 34 moves to the position close to 31 first watch from piston, thereby, by passage 32 sealings, makes when piston 31 advances, and the content of sleeve 33 only can advance to syringe ports 36.

Unlike commercial syringe, wherein before filling processing, make up a prescription end or relative syringe needle are exposed to non-sterilizing zone, and in current configuration, cap is removed from end 36 just before use and only after filling processing.Box can pass through multiple device known in the art, for example comprises, and Rule adapter, barb adapter, interference fit adapter, diaphragm apparatus, couple pipeline and couple mutually with syringe, or bonded to one another.In a kind of configuration, box is arranged in the hollow space in piston.

With reference now to Fig. 4,, show a kind of configuration, wherein box 10 is connected to the rear end of piston 43, and extends from piston 43 with horizontal direction.Valve 44 is arranged in the rear end of fluid passage 42, allows fluid to transfer to sleeve 40 from box 10, but stops fluid along flowing in the other direction, therefore makes whole dosage when piston-advance only flow to the end 45 that makes up a prescription.In a kind of configuration, piston 44 also allows air after box 10 is emptying to enter flow channel 42, therefore makes fluid advance to sleeve from passage.In one embodiment, after the emptying useful medicament of described box, the special sterile compartment allows water or air to enter fluid passage 42 after useful medicament, in order to wash the useful medicament of the remnants in passage.In a configuration, described water or air compartment are the parts of box 10 assemblies.

Fig. 5 a shows ejector filler, and it comprises the box 10 in the pressure chamber 51 be arranged in infusion appliance body 52.Box 10 comprise with infusion appliance body front end link without pintle-type nozzle 17.Piston 53 is arranged in body 52 and by (peruse) position before keeping (detaining) mechanism (not shown) to remain on it using, and the volume of being setovered forward with emptying pressure chamber 51.In a kind of configuration, box 10 comprises the compartment more than before use, and carries out with the similar process of describing in Fig. 1, these compartments manually being mixed after removing box 10; Then replace the box 10 in body 52.

Fig. 5 b shows infusion appliance 50, its piston 53 from arrestment mechanism (detent mechanism) thus discharge and by spring 54, pushed to and pressure chamber 51 exerted pressure cause box wall collapse (collapse) and by after the content of nozzle 17 delivery cassettes 10.Before use, nozzle 17 can be always by protecting without cap or bonding paper tinsel.

Fig. 6 show with Fig. 5 in configuration similarly configure, except piston is pressurized gas is setovered forward, this gas-pressurized is produced when it is started by hand switch 62 by explosion type module (pyrotechnic module) 61.

Fig. 7 shows box 70, and it is made by pipeline section 71, and in pipeline section 71, at 72 places, a plurality of positions along pipeline section 71, this pipeline section 71 is stressed and heat seal 72, the compartment that comprises useful medicament to form at least one.In a kind of configuration of box 70, the sealing at compressed position 72 places is frangible, and it is formed and makes them to peel away when having threshold pressure or power.Pipeline section 71 can be made by extrusion, injection molding, blowing or other manufacture method known in the art.In a kind of configuration, pipeline section 71 comprises a plurality of layer, and wherein internal layer is heat seal mateiral, and at least one second layer provides the barrier properties of improvement, to reduce some gas or dampness, crosses over tube wall and shifts.In a kind of configuration, pipe is that co-extrusion forms (co-extruded).In a kind of configuration, at least one ground floor of tube wall is made by the rolling sheet of plastics, metal or metal-oxide, and at least one second layer is squeezed on the ground floor of described rolling.

Fig. 8 shows the needle-free jet infusion appliance configuration that is similar to the configuration of showing in Fig. 5, except box 80, by pipeline section, is made, and nozzle 17 is attached to beyond its front end.

Fig. 9 a shows syringe and case assembly, and it is similar to the configuration of showing in Fig. 3, and being made by pipeline section 90 except box 90, this pipeline section 90 is in two positions 99 ' and 99 " ' locate to be stressed and seal to form compartment.Sealing 99 ' is the frangible part, and it is pressed and content can ftracture when pressurized at box, and to allow fluid flow between syringe and box, recessed luer lock connection 92 is attached to box at the one end.Pipeline section, in some configurations, box 90 can be in use between before be held in syringe always and be separated.The sterilizing state of product and device can be realized with similar mode and the measure described in Fig. 1 to Fig. 3.Tube wall can be in conjunction with single layer or a plurality of layer, and with in conjunction with high-barrier PCTFE layer, aluminium lamination, COC layer and peelable adhesive linkage.

Fig. 9 b shows other configuration, and wherein, box is made out of tubes, in this pipe, first sealing the 99 ' and second sealing 99 " limit the first compartment 95, the second sealings 99 hold the first material " and the 3rd seal 99 " ' restriction holds the second compartment 94 of the second material.The second sealing 99 when any one or both in the first compartment 95 and the second compartment 94 pressurize " may ftracture, to allow the first material and the second material, merge.The first sealing can be ftractureed, between box and syringe 97, to form fluid flow.This box further comprises peelable obstruct shell 96 ' and 96 ", it seals and crosses over the first and second crush seal sections 99 ' and 99 each other "; Strengthened the obstruct between box environment and the first compartment 95.In the situation that the barrier properties of pipe 93 is not enough to prevent that the first compartment 95 from suffering dampness, oxidation or illumination, this configuration can be especially favourable.

This tube material is preferably transparent, and to allow the visual inspection content, this endangers a part of barrier properties usually.Therefore peelable shrinking away from theshell can comprise the high-barrier aluminium lamination, and it prevents visual inspection box content, and need to peel shell off and could check.The first tab (tab) 98 ' and the second tab 98 " be provided, respectively as the first and second peelable shrinkings away from theshell 96 ' and 96 " extension so that peel shell off with finger.This peelable shrinking away from theshell can be to be pre-formed as adapting to the shape of the first compartment 95.Peelable shrinking away from theshell 96 ' and 96 " at least one can be extended to form the obstruct shell of the second compartment 94.Can be by peelable shrinking away from theshell 96 ' and 96 " at least one extension; but so that the printable or surface of labelling otherwise to be provided; comprise the machine-readable data representation of figure, text, bar code or other optics, it shows the data of content about box, operational order, warning etc.Peelable shrinking away from theshell can be made by single or multiple lift film or paper tinsel (be referred to as " thin slice "), and can comprise pressure adhesive, static bonding agent or responsive to temperature bonding agent, to form pealable seals.

Figure 10 a illustrates another kind of preferred disposition 100, and wherein the second compartment 16 comprises strippable coating 105.For different application, expectation makes at least a portion of packing be made by transparent material, for example, in expectation vision (or passing through optical instrument), check in one or more compartments or the application in the content of the merging compartment by after the combination of two or more compartments.Yet the normally transparent material has higher moisture transfer rate (MVTR) than opaque paper tinsel, thereby provide lower obstruct between the environment of compartment and packing.Some products are extremely responsive to dampness, and such as dry vaccine, its drug effect may suffer damage because of the relative humidity level higher than 2% or 3%.It is also important to note that, visual inspection vaccine powder before use, to guarantee that product is not by the tampering mistake; And the dissolving fully that checks afterwards vaccine powder and diluent in mixing.

In a kind of configuration of present disclosure, box is stored in the outer package that comprises desiccant, to keep box dry environment on every side.In a kind of configuration, housing material is the type that is known as " removing film (scavenger film) " in industry, and desiccant material is embedded in the constituent (composition) of sheeting.In Figure 10 a, to pack 100 powder compartment and comprise that peelable height intercepts the layer 104 formed, this layer is opaque, or has limited optical transparency.In some configurations, strippable coating can provide the obstruct to light.The high-barrier transparent material is usually more expensive every transparent material than low-resistance.In some configurations, local strippable coating 104 is by making such as comprising daifluoyl (Aclar) high-barrier transparent material (Honeywell), and pack 18 ' larger shaping wall, by low barrier material, made, with the reduction manufacturing cost.Other desired characteristic that strippable coating 104 can provide shaping wall 18 ' to lack.Strippable coating 104 can be a part of manufacturing the raw-material composition of shaping wall 18 '.Strippable coating 104 can be made by the thin slice of the separation of the first wall 18 ', and, in a kind of manufacture is arranged, two thin slices are formed into together.In some configurations, its mesospore 108 ' is the film of thermoformable, and strippable coating 104 is paper tinsels of cold forming, and formation processing can comprise and combined cold forming and hot formed step.

In some configurations, the chamber 105 in strippable coating 104 forms with the wall 18 ' that is shaped and is separated, and is attached to packing with sealing means subsequently.Strippable coating 104 is attached to packing can be by a kind of realization in means known in the art, and that these means comprise is bonding, gummed, pressure-sensitive adhesive, hot melt welding, ultrasonic fusing etc.In a kind of configuration, strippable coating 104 is sealed to the first wall 18 ' via die-cut adhesive sheet.Die-cut bonding agent can bond to the first wall 18 ', and, at subsequent stage, strippable coating 104 is attached to it.Alternatively, die-cut bonding agent can bond to strippable coating 104, and, at subsequent stage, the first wall 18 ' is placed to and is attached to this bonding agent.Strippable coating 104 can comprise aluminum lamination or aluminized coating.

Configuration 100 further comprises the port compartment 103 that makes up a prescription, and its port that will make up a prescription maintains in aseptic cover until use constantly.The port compartment 103 that makes up a prescription is formed in the extension 101 of sheeting of packing.Provide and torn off otch 102, thereby exposed in order to easily remove extension 101 port that makes up a prescription.Thereby Figure 10 b shows the configuration 100 after removing strippable coating 104 and allow to observe by transparent wall 18 ' vision the content of the second compartment.In addition, extension 101 has been removed, and exposes the port one 2 that makes up a prescription of recessed luer lock connection form.In some processes, be desirably in before removing extension 101 and merge

compartment

15 and 16, with the exposure that minimizes the port that makes up a prescription with reduce pollution risk.The second wall 18 of packing 100 " preferably by making such as lamination aluminium foil, SiOx laminate, AlOx laminate or the such high barrier material of other materials known in the art.

In some configurations, the second compartment 16 is depressed, so that first between the first compartment 15 and the second compartment 16 intercepts 19 ' cracking, so that two compartments merge; And make second between the compartment (15+16) of the second compartment 16(or merging intercept 19 " cracking.The order that the preformed configuration of the second compartment 16 allows to be scheduled to and timing controlled

intercept

19 ' and 19 " each cracking.The darker form of compartment 16 makes when compartment 16 is depressed at its far-end 106 places, the tension force (strain) at this regional 106 places of the first wall 18 ', the first wall 18 ' and second wall 18 in contiguous this zone 106 " sealing relax; And the proximal end region 109 contrary with depressing district's band 106 of the first wall 18 ', and the first wall 18 ' and the second wall 18 " between be adjacent to described proximal end region 109 sealing be tensioned; Cause the first obstruct 19 ' cracking, and the second obstruct 19 " remain intact.

In step subsequently, the compartment (not shown) of merging is pressed at its proximal end region, so that the second frangible part 19 " on overtension, make its cracking, with the formation fluid between port that makes up a prescription, be communicated with merging compartment.As the additional or alternative of sterile dispensing port compartment 103, port can sterilely seal by paper tinsel section, obturator (such as the rubber obturator) or any other mode known in the art of stopper (such as protruding Rule lock nut), welding.If other seal members are sterilely protected content and prevented that it from overflowing, can cancel the second frangible part.

Figure 10 c is to a kind of mode of scheming l0e and showing operating case 100, and its straightforward manipulation by operator's thumb is realized frangible part 19 ' and 19 " controlled orderly cracking.Box 100 is shelved in operator's palm on its forefinger and middle finger.In Figure 10 c, the second compartment 16 is depressed on its distal portions 106 by thumb.As a result, the wall 18 ' at proximal end region 107 places of the first compartment 16 is tensioned, and the first fragile section 19 ' is applied to peeling force.Therefore simultaneously, thumb pressing down on the remote area 106 of the second compartment 16 prevented that regional tensioning of the first wall 18 ', to the second fragile section 19 ' ' peeling force be eliminated or minimize.As a result, shown in Figure 10 d, the first compartment and the second compartment become merging compartment 16 ', and the second frangible part 19 " remain intact, make the material of the first two compartment that can be communicated with the port that makes up a prescription at the product that can make up a prescription mix.The configuration of figure l0d allows box is put aside, and for example, in order to allow material thoroughly mix, and do not have, is not exposed to pollutant part risk, because the port that makes up a prescription still is sealed in the port compartment 104 that makes up a prescription, and the compartment 16 ' merged still is not connected with the port that makes up a prescription.

In Figure 10 e, the port compartment that makes up a prescription is ripped, and port one 2 engages with syringe 108.Depress the compartment 16 ' of merging with thumb at near-end 107 places of the compartment 16 ' merged, cause the wall tensioning at far-end 106 places of the compartment merged, and at the second frangible part 19 " on apply peeling force, make the second frangible part 19 " cracking set up fluid and be communicated with between the compartment 16 ' of syringe 108 and merging via the port one 2 that makes up a prescription.In other configurations, pressing down of compartment is by compressed object, such as flat board or roller, completes.This disclosure has advantageously been instructed for filling the medicine kit of infusion appliance; wherein box is communicated with only foundation after in hermetically enclosed mode, protecting infusion appliance and box with the fluid between infusion appliance; limited and can inject product and be exposed to non-sterilizing territory, and reduced the risk that product overflows.Usually for bottle and ampoule, the fluid connection is to set up during the combination of infusion appliance and box, and this combination is usually stung diaphragm seal by minute hand and realized.

Figure 11 shows a kind of configuration, the second wall 18 of its intermediate package " comprise strippable coating 111, for the material in compartment provides the dampness strengthened obstruct.Shaping wall 18 ' is preferably formed by the aluminium lamination sheet of cold forming, and the high-barrier for dampness and gas is provided.Tab 112 makes the second wall 18 " more easily peel off.In some configurations, strippable coating 111 is by a kind of second wall 18 that is attached in manner known in the art (such as welding or bonding) ".In a kind of configuration, strippable coating 111 is the labels with pressure adhesive.In some configurations, pressure adhesive optionally is arranged on label, makes some zone of label there is no pressure adhesive.

Strippable coating preferably includes aluminium lamination, and it provided the height for dampness and gas to intercept before being peeled off.In some configurations, strippable coating is to manufacture the second wall 18 " the part of multilayer material constituent of thin slice.In some configurations, strippable coating is by from whole the second wall 18 " remove.In some configurations, scribing or die cut pattern limit strippable coating 111 by the zone be removed.In some configurations, the first wall 18 ' and the second wall 18 " the scribing section by scribing or die-cut, provide and be convenient to remove the tab of strippable coating 111 or disconnect tab.Box 110 can easily be attached to infusion appliance, drug delivery device, the reservoir of these or other system, or it can comprise the cover of removing before use.Strippable coating 11 can comprise printing (or otherwise labelling) information, and can after divesting, box 110 be attached at it people, device, the drug delivery device (such as syringe) of the content of receiving box 110, or file, as the label that presents this information.

Should be understood that according to present disclosure, other labels can be attached to box device, described label can comprise printing or the information of labelling otherwise; And can be not peelable or strippable and further be attached to other objects (such as people, device or file).In some configurations, the packets of information of box containing the part can tear or otherwise separate from the remainder of box so that in other places, such as on file, be attached to the patient with it or be attached on device, comprise or present this information.

Figure 12 shows a kind of configuration, and the port that wherein makes up a prescription is attached to the second wall 18 ' via flange 121 ' the outside.Flange comprises and wall 18 ' ' in the conduit (not shown) of register, it makes the content of packing be connected with the port that makes up a prescription.Port one 2 is by a kind of wall 18 that is attached in manner known in the art (comprising thermal welding or bonding) ".Box 120 can easily be attached to infusion appliance, drug delivery device, the reservoir of these or other system, or it can comprise the cover of removing before use.

Figure 13 shows a kind of configuration, and wherein box 133 links with manifold 134, and this manifold is arranged between syringe 131 and syringe needle (be depicted as by needle housings 132 herein and cover).This manifold comprises valve gear, at box 133, is activated (activate) afterwards, during this valve gear is drawn into syringe 131 by the content of box 133 when the piston of syringe is pulled out; And when piston forward moves, the content of syringe 131 is delivered to syringe needle.In some configurations, when from medicament extraction configuration, being converted to medicament injection configuration, the manipulation of manifold will cause box to break away from manifold 134.United States Patent (USP) the 7th, instructed for 879, No. 018 for realizing a plurality of manifoldings of same operation, and the full content of this patent is incorporated herein by reference.

The configuration of Figure 13 discloses a kind of configuration of uniqueness of pre-filled syringe, wherein before using piston in interior to position, for packing of product efficiency is brought Beneficial Effect.Needle safety feature and syringe disable feature can be attached in this configuration.United States Patent (USP) discloses No. 2009/0221962 and has instructed a kind of contraction type syringe and plunger.This syringe has sleeve, the contraction type syringe needle installed part that syringe needle maybe can be installed is installed, and plunger, this plunger comprises the spring, the device for engaging contraction type syringe needle installed part, integrally formed plunger seal and dismountable control device of initial compression, and this dismountable control device for contributing to the control to the contraction rate of syringe needle installed part when engaging with plunger.This syringe needle installed part is remained in sleeve by holding device, and this holding device prevents that when plunger is opened with filled syringe the non-of syringe needle installed part from shrinking intentionally.Holding device comprises a plurality of clips, and it can form with sleeve or can be arranged on the cap that is installed to sleeve.The displacer device also is provided, and pressing down of plunger can impel the displacer device that syringe needle is discharged from holding device thus, and allows thus the contraction of syringe needle installed part after spring presses down.In a kind of configuration of the present disclosure, box links with the syringe with disclose the contraction type syringe needle installed part of instructing for No. 2009/0221962 such as United States Patent (USP).

Figure 14 illustrates the box 133 that comprises the valve port one 41 be connected with syringe 131.In the step of using from the made up a prescription product loading injector sleeve of box 133, Rule cap 142 keeps putting in place.After the merging of the compartment by box 131 and the pop compartment merged and the obstruct of making up a prescription between port one 41, while with valve port one 41, making the retraction piston when syringe, the product that can make up a prescription will flow to syringe sleeve from box 133, and when piston-advance, the product that can make up a prescription is pulled to injector tip, and can not return to box.In a kind of configuration, band valve port comprises check (non-return) valve, and it allows fluid to flow out box 133, and prevents reverse inflow box 133.In a kind of configuration, with the valve port for example by rotation, move axially or these combination carrys out manual operation, to switch between open mode and closed condition.

In some configurations, box can be removed during manual operation or after manual operation.United States Patent (USP) the 7th, instructed for 879, No. 018 for realizing the multiple manifolding of this point, and the full content of this patent is incorporated herein by reference.In some configurations, syringe 131 is equipped with valve, makes and do not allow any end that flows through syringe when the retraction piston of syringe, and allow the mobile sleeve that flows out syringe when piston-advance.In some configurations, the valve of described syringe is check (non-return) valve.In some configurations, the valve of syringe is manually actuated.In some configurations, the band valve port one 42 of the valve of syringe and box is got up by mechanical connection, makes operation tape valve port one 42 that it is closed, and the valve of meeting operating syringe is opened it, or vice versa.Making up a prescription end in can not receiving box the time, for example in the situation that the end that makes up a prescription in conjunction with giving as security pin (staked needle), contraction type syringe needle or other release mechanism, the configuration of Figure 14 can be especially favourable.

United States Patent (USP) discloses has instructed a kind of contraction type syringe, plunger and releasable syringe needle fixation kit for No. 2011/0015572.The contraction type syringe typically has the glass sleeve and pre-filled before use fluid contents is arranged.Releasable syringe needle fixed system comprises contraction type syringe needle, needle seal, fixed component and can operate the displacer member that the contraction type syringe needle is discharged from fixed component.Fixed component has matching surface, for being installed to the complementary fit surface of syringe sleeve inwall.Plunger comprises plunger outer shroud (outer), the plunger rod that is connected to frailly control member, spring and can engage the whole plunger seal of contraction type syringe needle, and wherein plunger rod, plunger outer shroud and control member co-operating are to maintain releasedly initial compressed state by spring.After sending the fluid contents of syringe, plunger forces the displacer member that the contraction type syringe needle is discharged from fixed component.Contribute to the contraction of contraction type syringe needle when engaging with whole plunger seal at the decompress(ion) of the end of depresses plunger spring.The double locking system prevents from shrinking reusing of syringe afterwards at syringe needle.In a kind of configuration of present disclosure, box 133 is via associating with valve port one 41 devices and the sleeve that discloses the safety injector of No. 2011/0015572 instruction such as United States Patent (USP) in Figure 14.

With reference now to Figure 15,, in some configurations, expectation lyophilizing (lyophilization) is the material in compartment 15 directly.The first wall 18 ' is preformed and is fused to the second smooth wall 18 ".The first compartment 15 is beginnings, and is longer than final, the closure size of this compartment.This compartment 15 reserves sufficient space for the filling liquid material.Then this box is placed in freeze dryer until frozen dried completes, and at the place, bottom of the first compartment 15, stays dry block.This compartment is then sealed sterilely to hold the medicament of lyophilizing.The second compartment 16 can be filled and seal before or after frozen dried.

With reference to Figure 16, the box 160 of another kind of configuration is shown, it comprises the first compartment 15 of preserving the first material, and preserves the second compartment 16 of the second material; These compartments are separated by frangible part 19 ', and this frangible part 19 ' can ftracture to allow the first material and the second material to merge.The second compartment 16 is by the second frangible part 19 " be separated with recessed Luer lock adnexa 12, this second frangible part 19 " can ftracture to allow box and such as the fluid flow between the dispensation apparatus of syringe or infusion appliance.Adnexa 12 comprises fluid passage 161 and is arranged in the static mixer 162 in this fluid passage 161.This configuration makes, and when the first material merged and the second material are transferred to dispensation apparatus from box 160, static mixer strengthens the mixing of these materials to form more uniform product.At United States Patent (USP) the 4th, instructed the example of static mixer in 538, No. 920, the full content of this patent is incorporated herein as a reference.Mixture can further shift back and forth between delivery apparatus and box, to repeat to mix action at the static mixer place.In some configurations, static mixer is configured to by welding and is pre-formed the channel pattern that the appointed area of wall forms between the wall of flexible package.Static mixer can be only narrow nozzle or the porous member in the flow channel be contained between box and delivery apparatus.

Figure 17 shows preferred embodiment, and wherein box 170 comprises compartment 171, and it comprises the first material, and by frangible part 19 " with recessed Luer lock adnexa 12, be separated.This adnexa comprises fluid passage 161 and is arranged in the static mixer 162 in this fluid passage 161.The syringe 173 that comprises the second material 174 is attached to box 170.Frangible part 19 " can ftracture to allow the first material and the second material to merge.By pulling syringe piston, the first material is retracted to from compartment 171 syringe and with the second material in syringe to be merged.The piston of syringe can operate back and forth, transfers to box 170 neutralizations with at least a portion by mixture and migrates out from box 170, generates more uniform mixture when material flows through static mixer 162.In a kind of configuration, the expansible total capacity to being enough to receive the first material and the second material of compartment 171.In some configurations, box 171 can be included in the first compartment 171 with syringe, merge before or after can with the first compartment 171 merge more than the compartment of.It will be apparent to those skilled in the art that static mixer can be similarly to be configured in the previous configuration of present disclosure and to realize with Figure 16 or Figure 17.Especially, refer back to Fig. 3 and Fig. 4, static mixer can be arranged in the bar or plunger of syringe.

Figure 18 shows the box 180 of another kind of configuration, comprise the first compartment 15 that comprises the first material, the second compartment 16, the static mixer 184 that comprises the second material, this static mixer is arranged between the first compartment 15 and the second compartment 16, be separated by frangible part 181 and the first compartment 15, and be separated by frangible part 182 and the second compartment 16.When the first material and the second material mix, the first frangible part 181 and the second frangible part 182 split, make upper wall 183 be re-arranged to shown in dotted line 183 ' like that, to allow the first material and the second material, via static mixer 184, be communicated with.The first compartment 15 and the second compartment 16 are not complete expansion, because the sunk area 186 of the first sunk area 185 of the first compartment 15 and the second compartment is expansible to receive the material from another compartment; Therefore the good mixing of the first material and the second material can be by alternately compressing the first compartment 15 and the second compartment 16, and the mixture that shifts the first and second materials by static mixer 184 is realized.Static mixer 184 is shown as porous body herein, and can be replacedly other static mixers known in the art.

The 3rd frangible part 19 " can ftracture, to set up being communicated with between mixture and adnexa 12.This configuration further comprises the backing 187 of supporting case 180, and rocking bar, this rocking bar comprises the first compressive plate 188 ' and the second compressive plate 188 ", it is removable comes with respect to backing 187 rotations, with alternately use the first plate 188 ' press the first compartment 15 and with compressive plate 188 " press the second compartment 16.The configuration of rocking bar and backing by more effectively and symmetrically compress

compartment

15 and 16 and the transferring content thing contribute to the efficient operation of mixed processing by static mixer 184.When mixture is ready to transfer to dispensation apparatus by adnexa 12, the first compressive plate 188 ' can be placed in the first emptying place of compartment 15, and therefore all mixture all are discharged to adnexa 12 from the second compartment 16 basically.Rocking bar can link via hinge or hinges and backing 187, and its can with by manually or operate by device.

Figure 19 shows the box 190 of another kind of configuration, and it comprises the first compartment 15 that comprises the first material, the second compartment 16 that comprises the second material, and between the two preformed cross aisle array.This preformed cross aisle array provides static mixer to strengthen mixing of the first and second materials when between the first compartment 15 and the second compartment 16, carrying out transmission back at the first and second materials.

With reference now to Figure 20 a to 20e,, described a kind of possible manufacture of described box and processed.In a kind of configuration, this manufactures while processing and completes by shaping-filling-sealing system.

Figure 20 a shows the preform flexible wall 18 ' of the packing of the component for storing useful medicament, comprise the first chamber 15 for receiving the first component, for the second chamber 16 of receiving second component and the first uninterrupted zone between the former two, for receiving the adnexa chamber of adnexa, and second between described the second compartment 16 and described adnexa chamber 203 uninterrupted regional 19 ".The first compartment manufactures the material of reception nonfluid or the material of poor fluidity, such as powder, compression or agglomerating powder, granule, spherolite, solid, fritter, capsule, slurry, paste, high viscosity fluid, Emulsion and above combination.The first material is filled into the first compartment by the fill system of the type of the material that is suitable for needs and fills.The second compartment 16 can be filled water or other low viscosity fluids, but fill up chamber 16 fully, may be challenging, because the surface tension of fluid and other characteristics may cause overflowing.

Another challenge is that one of them factor is with fluid-filled chamber 16 time, will avoid bubbling or formation of foam because a plurality of factor fluid filled are relatively slow manufactures to be processed.In a kind of configuration, this challenge solves by following operation, the aliquot of frozen liquid (aliquot) in the mould of the shape that preferably has the second compartment 16, then be transported to these in chamber as solid by a kind of mode known in the art.Fill system is designed so that, the aliquot heat transmission of frozen liq is limited, and makes this aliquot keep being essentially solid until the second chamber 16 is sealed; Freezing liquid can thaw afterwards.Can be quite low by all the time temperature being controlled in reason herein, and select to have the packing contact material of suitable heat transfer coefficient, be limited in to fill during processing freezing aliquot heat is transmitted.Before introducing the second chamber 16, can check freezing liquid aliquot for weight and other characteristics and parameter.

In a kind of configuration, will be filled into more than the freezing aliquot of the second compartment 16, these freezing aliquots can have identical, similar or different compositions.These aliquots can have complementary shape, and it can jointly form the shape of the second compartment 16 basically.In a kind of configuration, this aliquot directly in chamber 16 or the contrary flat wall 18 ' of packing ' freezing on (not shown).In another kind configuration, the second material is other forms of the loose powder dry matter that maybe can make up a prescription, and this may be that challenge ground is arranged for basically filling up the second compartment 16 fully.It may be also the limiting factor of manufacturing speed that loose powder is filled, and is a challenge for correct inspection aliquot filling medicament.In a kind of configuration, for the ease of powder, to fill, powder is compressed to form the tablet of loose conglomeration a little, or the integral type body, and is filled in the compartment of packing with that form by a kind of tablet filler device known in the art.In order to realize the conglomeration level of given compression ratio, may need special formula.Can be before the filling process of the second compartment 16 or during check tablet.

In a kind of configuration, after tablet is sealed in compartment, compartment by from peripheral operation with this tablet of disaggregation, therefore improve the substance dissolves (or dispersibility) with mixing diluents the time.Peripheral operation can comprise that the wall by packing is delivered to the integral type body by energy, and this transmission can be carried out but be not limited to following operation via at least one in following operation, and these operations comprise: the compression compartment; Vibration, comprise ultrasonic vibration, radio frequency vibration, acoustic frequency vibration; Compartment is applied to mechanical shock; Be exposed to high temperature or low temperature.In a kind of configuration, the integral type body be directly in chamber 16 or the contrary flat wall 18 of packing " form on (not shown).The first compartment 15 provides fills the low viscosity fluid effectively basically to fill up the another kind configuration in chamber 15.First fills well 201 ' and second fills well 201 " be pre-formed in the first wall 18 '; And the first preform is filled channel 202 ' and the second preform is filled channel 202 " they are connected to the first compartment 15.Figure 20 a shows the part of the thin slice that is formed the part (detail) that comprises a box.Will be by understood by one of ordinary skill in the art, according to normal manufacture custom, can be formed on the first thin slice 18 ' of larger extension (spread) for the array of the part of a plurality of boxes, and can process in formation subsequently and filling step simultaneously.

Figure 20 b shows the subsequent step of the manufacture processing of box 200.At the second compartment 16(, in this figure, be positioned on the opposition side of box 200) be filled and with lid thin slice 18 " after gas-tight seal, thin slice 18 " be sealed to the whole uninterrupted surface of the first wall 18 '.In a kind of configuration, the first thin slice 18 ' and/or the second thin slice 18 " internal layer comprise the binding agent with controlled peeling off (bonding) power, wherein lower seal temperature (for example 375 °F) causes strippable bonding (" frangible "); And that higher seal temperature (for example 450 °F) causes is permanent not peelable bonding.In a kind of configuration, in the sealing of first shown in this figure step, basically the uninterrupted surface of thin slice 18 ' all bonds to the second thin slice 18 " to form the frangible part; it is fully around the periphery of the second compartment 16; and, except filling channel 202 ' and 202 " basically around the first compartment 15 peripheries.Present the second thin slice 18 " be attached to the first thin slice 18 ', formed now the filling compartment and discharged compartment, it is communicated with the first compartment 15 via the channel formed between two thin slices.

The first filler opening 204 ' and the second filler opening 204 " can be at the second thin slice 18 ' ' put into the first wall 18 ' and be pre-formed before at the second thin slice 18 ", it is by manner known in the art, such as a kind of being pre-formed in punching, die-cut and cut.In a kind of configuration, fill the first compartment by the first filler opening 204 ' with the first material, and the second filler opening 204 " allow during filling from the first compartment 15 Exhaust Gas.During filling the filling source can with filler opening 204 ' and 204 " at least one associate to help that material is introduced to the first compartment and by discharging the compartment extracting gases.In a kind of configuration, filling coupler is syringe needle or pipe, and it is bent to arrive in the first filling channel 202 '.

In a kind of configuration, to fill coupler and there is columniform end, its diameter is greater than filler opening 204 ', makes its tight fit and liquid seal when putting into filler opening 204 '.In a kind of configuration, filler opening 204 ' and 204 " not preformed, but sharp-pointed implant (such as hollow pinhead) pierces through the second wall 18 with fluid sealing mode ", penetrate into and fill well 201 ' and 201 " in.Rear a kind of configuration is especially useful, because packing is gas-tight seal before putting into component, and putting into of component can be carried out on the different piece of interstitial wire or on not collinear.Pack and can be stacked up between sealing step and filling step.In a kind of configuration, filling well 20 and 201 " at least one in rubber or semi-rigid sealing member are set, be formed for the interface in the source of filling, to contribute to fill the sealing of coupler to box.In a kind of configuration, the cross-sectional area of channel is enough little, to prevent that filler is because the surface tension of material is overflowed the first compartment 15.

In a kind of configuration, check (non-return) valve is arranged on the first and

second filling wells

20 and 201 " at least one in, to control material to flowing in the first compartment 15.The semipermeability object can be arranged in fill port 201 and fill in channel 202, spills to allow gas during filling, and prevents that material from leaving the first compartment 15.In a kind of configuration, discharge the first the mobile of chamber 15 and be monitored during filling, and fill and interrupt when the discharge fluid converts filler to from gas.The first filling channel 204 ' manufactures and makes the material that enters the first compartment at the second wall 18 " the upper slip, therefore prevented the foam of not expecting or the foaming that injection, injection may cause filling medicament to produce.Special-purpose air deflector can be arranged on fills channel 202 or fills in well 201, to promote the slip of filler on the wall of the first compartment 15.

Figure 20 c illustrates the subsequent step that box 200 is manufactured.In the second welding step, channel (202 ') and (202 ") are pressed down and welding, seal up the first material in the first compartment 15 fully.Seal temperature can be higher than frangible part fusion temp, to avoid the cracking of channel (202 ') and (202 ").In a kind of configuration, this sealing step further is applied to the periphery of box 200, and at least some zones in the zone that earlier is sealed into the frangible part are applied to the permanent seal characteristic.Sealable plug-in unit can be arranged in channel, to promote welding and the sealing of channel.

With reference now to Figure 20 d,, a kind of by manner known in the art, comprise punching press, chi steel cutting (ruler steel cutting), cut etc., from chip edge, prunes out box.

Will be by understood by one of ordinary skill in the art, above disclosed manufacturing step order can all or part ofly change, to adapt to best particular design, application and manufacturing equipment.

Before frangible part welding step or during, before sealed-for-life welding step or during, or (comprised by adnexa welding mode known in the art, for example, hot melt welding, pulse welding, vibration, ultrasound wave, RF welding, with the light beam welding) in a subsequent step carried out, adnexa 12 be welded to and at the first wall 18 ' and the second wall 18 " between.

Figure 21 a illustrates the decomposition view of syringe 210, and this syringe 210 comprises the static mixer for compounding substances.In a kind of configuration, the first material is included in syringe 210, and the second material is transferred to syringe from the box (not shown), and in syringe, the second material mixes with the first material.In another kind configuration, at least the first material and the second material, from one or more boxes the not homology of material (or from), are transferred to syringe with being pre-mixed respectively or, and in syringe, mixed processing is applied to described material or mixture.In some configurations, box is to associate with similar mode and the syringe 210 of Fig. 2,3,4,13 or 14 layout.Plunger 214 is arranged in syringe sleeve 212 in a fluid tight manner movably.Piston 213 is arranged in the looping pit of plunger 214 in a fluid tight manner and in mode movably coaxially; Piston further comprises the static mixing plate (or static mixer) 217 from the far-end horizontal expansion of piston 213.Localized axial groove 215 in the looping pit of plunger 214 is manufactured into the laterally projecting brake tooth (detent tooth) that receives piston 213.

Figure 21 b shows the sectional view of the mixing syringe 210 that comprises the first material 218.

Figure 21 c illustrates the sectional view of mixing syringe 210, and wherein piston is to the far-end indentation of sleeve 212.Static mixer promotes plunger and piston, makes the second material enter sleeve 212 to form mixture 218 '.The source of the second material does not illustrate, but as mentioned above, it may be the box that the syringe 210 in a kind of configuration provided with present disclosure is associated.Should be understood that if the second material does not enter syringe 210 from Luer end, for Luer end, cap, cover, valve or the sealing of another kind of device, make flowing of not occurring from end during retraction piston.

Figure 21 d shows blend step, and wherein piston 213 moves around, and mixture 218 ' is turned to, and to flow through the opening in static mixer 217, and has strengthened the mixing of mixture 218 ', to form uniform product.Brake tooth 216 is not shown with axial groove 215() align, make piston to move freely with respect to plunger 214.Plunger can freely slide along sleeve, and compensates the bar of (compensate) piston when it moves in the sealed volume between sleeve 212 and plunger 214 or shifts out the sealing volume.In a kind of configuration, piston is rotatable further to strengthen mixing.In a kind of configuration, the static mixing plate, by another kind of static mixer known in the art, such as porous material, substitutes.In a kind of configuration, piston is by the device operation such such as controlled electric performance device.Injector tip and preferably be closed (tap) for other ports of syringe during mixed processing, to avoid mixture 218 ' to overflow or material is incorporated in sleeve 212.

Figure 21 e illustrates syringe 210, and wherein retraction piston, make brake tooth 216 enter axial groove 215(not shown); And piston is rotated, make brake tooth 215 engage with the axial groove 219 of plunger 214, now plunger 214 is joined together securely and can moves integratedly with piston 213.In a kind of configuration, sleeve and plunger comprise that nonaxisymmetrical cylindrical profile is to avoid plunger because the rotation of piston 213 is rotated.In a kind of configuration, plunger 214 comprises that hard core is to promote and the engaging of piston 213.Because the end of syringe 210 is not closed (untapped), by making piston 213 and plunger 214, towards the distal advancement of syringe 210, distribute mixture 218 '.

Figure 22 a, and the partial cross section in Figure 22 b illustrates and the box of giving as security needle injection and being associated.Box 10 comprises the first material compartment 15 and the second material compartment 16 that the obstruct 19 ' by ftractureing is isolated.Box 10 further comprises adnexa 222, for the content that makes box 10, with signature needle injection 221, is communicated with.The near-end 224 of adnexa 222 is sealed in the first wall 18 ' and second wall 18 of box 10 " between; and by the obstruct 19 ' that can ftracture ' isolated with the second compartment 16, the obstruct 19 ' that this can ftracture ' by directly sealing the first wall 18 ' and the second wall 18 " form.The far-end 223 of adnexa 222 is manufactured into the end that receives removably in a fluid tight manner syringe 221, and the near-end 224 of adnexa 222 is manufactured into the end that receives syringe needle 225 and it is protected.Passage 226 in adnexa 222 is communicated with between the content of syringe needle and box 10.Box 10 provides the aseptic syringe needle protector to syringe needle 225.

In a kind of configuration, initial needle protector (not shown) is removed from syringe, and is substituted by box 10.In the second obstruct 19 " split after, the content of box 10 is transferred to syringe 221.In some configurations, during manufacture process, box 10 is installed on syringe.In a kind of configuration, box 10 only has single compartment.In a kind of configuration, box has at least two compartments, and these compartments merged before the content of box 10 is transferred to syringe 221.In a kind of configuration, syringe 221 comprises release mechanism, and it is retracted into by least a portion of syringe needle 225 position that prevents that syringe needle from jabbing when injection finishes.In a kind of configuration, syringe 221 comprises that syringe needle jabs release mechanism, and its injection at content is protected needle point after having completed at least in part.

Typically, for pre-filled syringe, syringe is fed to fill unassembledly and processes, and syringe assembles fully after content has been filled.The configuration of Figure 22 a and Figure 22 b provides favourable manufacture method, when wherein (a) syringe 221 is supplied, has assembled and has completed, and (b) with the content of expectation, fill and seal box 10, and (c) box 10 is assembled.This processing can complete under aseptic environment, or product can finally be sterilized.Therefore, this approach allows to produce pre-filled injector assembly, and it does not need actual syringe part assembling.In addition, when we need special syringe label or packing that content information is provided, but box labelling or label have this content information.The label of box 10 or the part of label can be transferred to syringe, after box 10 has removed, to maintain product identification.

Figure 22 a and Figure 22 b show the box 10 with two annexable material compartments, yet it will be apparent to one skilled in the art that box 10 only can comprise a compartment or more than two compartments.Being connected between syringe 221 and adnexa 222 is shown as being slidably matched of fluid-tight, yet can comprise that other mating features are to help sealing, assembling or to remove, for example comprise screw thread, spiral slope, Rule cooperation, Luer lock cooperation, O shape ring, rubber seal parts, interlocking elements, buckle (snap) parts, other features that contribute to fluid-tight, removable connection or above combination known in the art.The far-end 224 of adnexa 222 can closely be engaged in syringe needle 225 around, fluid-tight is provided, it prevents that the content of box 10 from arriving the space between described adnexa 222 and syringe needle 225; And prevent that air from arriving syringe needle from that zone.Adnexa can be made by elastomeric material at least in part.It will be apparent to one skilled in the art that adnexa 222 can be designed to be able to difference with respect to syringe towards accommodating box 10, and, in a kind of configuration, box 10 and syringe 221 can be overlapping or placed side by side at least in part.The piston of syringe 225 and sleeve can be sealed the proximal end at them by sterile film 229, make before use the content contact surface keep sterilizing and without the sterilizing outer package always.

With reference to figure 23a and its local amplification sectional view in Figure 23 b, the another kind of preferred arrangements that shows box and give as security needle injection.Give as security pin jointer 237 and be axially disposed within around syringe needle 225, and be connected in a fluid tight manner the end of syringe 221.Jointer 237 protection syringe needles are avoided physical injury, and protect operator and object to avoid unexpected acupuncture.The far-end of syringe needle 225 is further supported by central slide body 238, coaxially is arranged on movably in jointer 237 around syringe needle 225.The adnexa 232 of box 10 comprises near section 234 of being attached to the box wall and the far-end 233 with elongated cylinder, and it can axially be inserted into syringe jointer 237.Utilize this layout, syringe needle 237 keeps being protected, until assemble with box 10.

Figure 23 c and its amplification partial cross section in Figure 23 d illustrate the device of Figure 23 a and 23b when injector assembly 231 and case assembly 10 are joined together.The far-end 233 of adnexa 232 is inserted in jointer 237, promotes central part 225 to expose quite a few of syringe needle far-end, and needle pierces accessory passageway 236 is set up fluid and is communicated with between syringe 221 and box 10.Fluid-tight can provide by closely cooperating between syringe needle 225 and adnexa 237.Adnexa 237 can be made by elastomeric material at least in part, the sealing with enhancing with syringe needle 225.Adnexa 237 can further comprise sealing far-end 233 or elsewhere along the film (membrane) of passage 236, further strengthens the sealing between adnexa 237 and syringe needle 225, and further maintains cleaning of passage 236, until itself and box 10 assemble.

The content of box 10 is sucked in syringe 221.As substituting of the sealing between syringe needle 225 and adnexa 237, sealing can be formed between (a) central part 238 and jointer 237, (b) between central part 238 and syringe needle 225, (c) between the end of syringe 221 and jointer 237, and (d) between adnexa 232 and jointer.In some configurations, before content is transferred to syringe 221, two material compartments in box 10 or more compartments merge, and allow to mix.In some configurations, before the product merged in suction, the material in syringe 221 is transferred and merges with the material in box 10.For example, box 10 can comprise dry matter, and syringe 221 can comprise diluent; Diluent is transferred to box 10 and is allowed powder dissolution, and; Syringe is got back in the product or the transfer that merge, is assigned to object, or transfers to another device.In a kind of configuration, use the material pre-filled syringe, and the content of box 10 is transferred to syringe 221, the material merging in permission content and syringe 221.

Figure 23 e, and its amplification partial section in Figure 23 f, show the configuration of Figure 23 c and Figure 23 d when box removes.Jointer 237 is retained on box 10, and syringe 221 now when preparing injection syringe needle come out.In a kind of configuration, mechanical interlocking guarantees that jointer 237 and box 10 keep together.This mechanical engagement can comprise screw thread, spiral slope, buckle, tight fit or other joints known in the art and separation characteristic.In a kind of configuration, when box 10 removes, jointer 237 remains on syringe 221, with continuation, to syringe needle 225, protection is provided and the protection that is not subject to the syringe needle injury is provided; And removed jointer before operator's injection.

Figure 24 shows another kind of configuration, and except rubber septum 241 is arranged in syringe needle end and spring 242 towards the far-end offset center part 220 and partition 241 of jointer 237, this arranges with the layout of Figure 23 similar.Syringe needle is by partition 241 sterile sealings.For material for transfer between box 10 and syringe 221, the far-end 233 of adnexa 232 is placed in jointer 237, barrier film and central part is moved backward, and make the passage 226 of ends exposed in adnexa 232 of syringe needle 225.When box 10 is removed, spring 242 makes barrier film return to cover the end of syringe needle 225, to syringe needle 225, provides protection to make it avoid mechanical wounding and pollution, until use constantly.Before using syringe 221, jointer 237 is removed together with partition 241 with spring 242, central part 220.

Figure 25 a shows pre-filled box, and it comprises coupler 250 and the packing associated via adnexa 257.The coupler assembly comprises needle assembly 253, and this needle assembly 253 comprises Luer lock hub (Lockhub) 255 and is attached to the rustless steel intubate (cannula) 254 on this hub.Needle assembly (or syringe needle) 253 is contained in the needle cap be formed in coupler 251.Coupler further comprises for making syringe needle 253 and packing 10 fluid passages that are communicated with 258.Be arranged on the sterile sealing that the rubber sheath 252 in described coupler 251 forms between needle hub 255 and coupler.The end of rubber sheath 252 forms the fluid-tight obturator of fluid passage 258, and it is pierced through to set up syringe needle 253 by intubate 254 and is communicated with the fluid between packing.The removable aseptic cover (closure) of Rule end 256 use of needle hub 255 seals, and the form of this aseptic cover is sealed foil, cover or other devices known in the art.Packing 10 comprises separates first can ftracture and intercept 19 ' between the first compartment that comprises the first component and the second compartment 16 that comprises second component, and described the first and second components can be combined can ftracture to intercept while ftractureing.In the another kind configuration, packing 10 comprises the single component of useful medicament.In another embodiment again, packing at least comprises the 3rd compartment that comprises the 3rd component, by the obstruct that can ftracture, that the 3rd compartment and the second or first compartment is isolated.The second obstruct that can ftracture 19 " obturator between the second compartment 16 and adnexa 257 is provided, adnexa 257 leads to the passage 258 in coupler 251.

Figure 25 b shows in the first and second obstructs that can ftracture and opens, thereby allows the first and second components to merge and set up after described mixture 16 ' and syringe needle 253 be communicated with via the fluid of coupler 251 configuration of Figure 25 a.This configuration provides simple pre-filled box, and it can be installed on standard Luer syringe 259 with the engaging of protruding Rule of syringe 259 via recessed Rule adapter of syringe needle 253.Then by the piston of indentation syringe, product 16 ' can be drawn in syringe, removable coupler is to expose syringe needle 253 for injection, as shown in Figure 25 c after this.In a kind of configuration, syringe can comprise the 3rd component, by product 16 ' being drawn in the syringe be partially filled, perhaps by first described the 3rd component being assigned to packing 10 from syringe, then the mixture suction being got back to syringe or, to different delivery apparatus, the 3rd component and product 16 ' are merged.Coupler 251 further provides backing for the part of packing 10.

Figure 26 illustrates the aseptic reconstruct box of pre-filled unit dose, comprise and be suitable for the packing 10 be communicated with syringe 260, this syringe 260 comprises Intradermal (ID) injection jointer (ID jointer), and this ID jointer comprises the outstanding guide plate (skid) 264 of the forward direction that contributes to the shallow insertion skin of syringe needle 262.United States Patent (USP) discloses the jointer that contributes to Intradermal to inject of having instructed likewise arrangement for No. 2010/0137831 and No. 2011/0224609, and this patent full content is incorporated herein as a reference.This ID jointer can be the whole ingredient of syringe 261 or be formed on the clip on the ID syringe.Form recess 267 in slide block 264, the adnexa of packing 10 265 is put on the needle hub 266 of syringe 260 contributing to.

Figure 27 a illustrates the box 10 be arranged on the ID syringe, and wherein box 10 and syringe 260 are placed to linear arrangement.This view provides the direction of the sectional view in Figure 27 b.Figure 27 b illustrates adnexa 265 and is press-fitted in the aseptic connection of formation on needle hub 266.The rubber obturator (stopper) provide the obturator for passage 272, and pierced through to set up syringe by syringe needle 262 and be communicated with the fluid between packing 10.

Figure 28 illustrates the configuration similar with Figure 10, except adnexa 281 be manufactured into make packing 10 be placed to be parallel to syringe sleeve rather than with syringe axis point-blank.

Figure 29 a and Figure 29 b show the box configuration that comprises coupler 293, and this coupler is communicated with intradermal needle assembly 291 and packing 10.Coupler is held needle assembly, and this needle assembly comprises intubate 292 and needle hub 291, and this needle hub is included in the outstanding guide plate of forward direction of its far-end and at Rule adapter at its near-end 297 places.Coupler 293 is used as without cap, and it engages with needle hub 291 in sealing area 299, maintains syringe needle 292 and guide plate zone sterilizing.Rule cap 298 sterilely seals Rule adapter 297 of needle hub 291, forms the box of integral sealing, and it keeps sterilizing and does not need the sterilizing outer package.Packing 10 and coupler couple together via adnexa 296.Adnexa preferably is heat fused to the wall of packing 10, and a kind of coupler that is connected in announcement manner known in the art (comprising that thermal welding, combination, close mechanical coordinate).Ftractureed sealing member 19 between the first compartment 15 and the second compartment 16 provides above-mentioned compartment and the isolated obturator of coupler 293.

Figure 29 b illustrates the device of Figure 29 a, and wherein Rule cap 298 is substituted by jacketed syringe 250, and the sealing member that can ftracture is opened to allow the component merging in the first and

second compartments

15,16 and set up to be communicated with the fluid of syringe needle via passage 295.Rubber obturator 294 will be constrained to the small volume of passage 295 in the dead band (dead space) of component in coupler, so limit the waste of product 15 '.This retraction piston that illustrates syringe is with the product 15 ' in the sleeve that receives syringe.Coupler is removed to expose syringe needle and ID jointer, for injection.Coupler 293, for packing 10 provides backing, contributes to press down the compartment of packing 10.

Figure 30 illustrates the similar box device 300 of box device 290 with Figure 29, except ID jointer 291 is arranged on needle hub 301.Needle hub 301, ID jointer 291 and coupler 293.

Figure 31 a illustrates box 310, and it has the device that major part is similar to the device 300 of Figure 30, except needle hub is arranged in ID jointer 313 movably, can between injection position and the discarded position of safety, move.Latch gear 315 keeps injection position.Spring can be arranged in zone 312 needle hub 313 is biased to the discarded position of safety.Figure 31 b illustrates the device 310 when lock pin has been operated with the release needle hub.Needle assembly, by indentation, takes the syringe needle end to closed section 316, has reduced the risk that syringe needle jabs.In a kind of configuration, needle hub for good and all is locked in this position, to prevent reusing of syringe needle.

Figure 32 illustrates box device 320, it is arranged on movably in coupler except needle assembly and can be mobile between primary importance and the second position, similar with the device 290 of Figure 29, wherein at primary importance place syringe needle end 292, do not pierce through obturator 294, perhaps only partly pierce through obturator, be communicated with the fluid of fluid passage 295 to set up at second position place syringe needle tip pierces obturator.

Figure 33 a to Figure 33 c illustrates pre-filled syringe 259, and it comprises common piston and jacketed syringe device, has the signature pin 334 for delivering drugs.Syringe cap 331 is communicated with syringe in the mode of aseptic joint.Cap 331 engages packing 10, to form removable box 330.The body of cap 331 is as the adnexa of packing and the coupler between syringe needle.Figure 33 d and Figure 33 e are illustrated in lay up period and are activated the amplification sectional view of cap afterwards when medicament are filled into the sleeve of syringe.This cap comprises rubber obturator 335, and it is pierced through by syringe needle 334.

To be it is apparent that to those skilled in the art, similarly configuration can be for other needle apparatus known in the art (comprising the syringe of carrying pipe, syringe needle with the soft sheath of protectiveness, muscle (IM) pin, subcutaneous (SQ) pin, Intradermal (ID) pin, miniature syringe needle, safty pin, contraction type pin, flushing needle etc.).

Syringe further comprises the aseptic cover 333 for sleeve, makes this injector assembly maintain sterilizing, and does not need the sterilizing outer package.

Figure 34 illustrates the device similar with the device of Figure 33, and it has added the vertically outstanding protective bulkhead 341 with the protection packing.It will be apparent to those skilled in the art that can be by the wall with extra, the flipover lid be associated with wall 341, slidably lid etc., further around packing, strengthens the protection to packing.

Any labelling of packing portability of device of the present disclosure, comprise printing, bar code, RFID label, embossment and engraving, with the information by expectation, conveys to people or device.This packing can be extended, so that enough labeled surface to be provided as required.

Compressive plate can associate with packing, to contribute to the compression at least one compartment of packing, or forces the obstruct cracking that can ftracture, or forces the product that can make up a prescription to distribute from packing.

Apparatus and method described above are applicable to other infusion appliancees or dispenser type, such as other devices of discussing in the ejector filler box of instructing in Fig. 1 or presents.In a kind of configuration, contraction type syringe needle mechanism, contraction type needle connector mechanism or other needle safety mechanisms and forbid again can being combined with mixing syringe described here mechanism with mechanism.

Box device of the present disclosure can combine with delivery apparatus or the applicator of several forms, to contribute to expect the use of form.Can comprise compressive plate or roller, with effective discharge of the content that promotes box.

Application of the present invention is not limited to syringe and ejector filler application, this syringe and ejector filler application provide as example, and instruction described herein can be applicable to other application, such as the aseptic filling of micropump reservoir, muscle automatic injector, Intradermal automatic injector etc.

Claims

1. one kind for having the box of the useful drug delivery device that can fill reservoir, and described box comprises:

Reconstruct formula unit dose packaging comprises:

The first compartment of at least the first component that comprises described useful medicament;

At least the second compartment of at least second component that comprises described useful medicament;

Be arranged in the adnexa on described packing, for described packing and the described reservoir of filling are joined.

2. box as claimed in claim 1, wherein said box is suitable for being communicated with the part of sending of described delivery apparatus, and described delivery portion is divided and is comprised a kind of in syringe needle, adapter, nozzle.

3. box as claimed in claim 1, wherein said delivery portion is divided and is comprised syringe needle, and described adnexa be sealed in described syringe needle around so that the fluid dead band minimize.

4. box as claimed in claim 1, further comprise the obstruct of ftractureing between described the first compartment and described adnexa.

5. box as claimed in claim 1, wherein isolated by described the first compartment and described the second compartment by the obstruct that can ftracture.

6. box as claimed in claim 1, at least a portion of wherein said packing comprises flexible wall.

7. box as claimed in claim 6, at least a portion of wherein said flexible wall comprises paillon foil.

8. box as claimed in claim 6, at least a portion of wherein said flexible wall is pre-formed at least a portion that limits described the first and second compartments.

9. box as claimed in claim 6, at least a portion of wherein said flexible wall comprises peelable foil layer.

10. box as claimed in claim 9, at least a portion of wherein said peelable foil layer is preformed.

11. box as claimed in claim 1, further be included in the fluid passage between described the first compartment and described the second compartment.

12. box as claimed in claim 11, further comprise the static mixer be arranged in described fluid passage.

13. box as claimed in claim 1, further be included in the fluid passage between described packing and described delivery apparatus, and be arranged in the static mixer in described fluid passage.

14. box as claimed in claim 1, wherein said packing comprises flexible wall, and this flexible wall forms at least a portion of the removable aseptic cover of described adnexa.

15. box as claimed in claim 1 further comprises and fills compartment, fluid passage and the first and second package wall that described filling compartment is communicated with described the first compartment fluid via described fluid filled passage.

16. box as claimed in claim 15, wherein said filling compartment is between the first and second walls of described packing.

17. box as claimed in claim 15, wherein said fluid passage is sealable to stop during filling or to flow to the backflow of described filling compartment after filling.

18. box as claimed in claim 15, further be included in the heat seal between the first and second walls of described packing, to seal described fluid passage.

19. box as claimed in claim 15, further comprise the isolating valve at least one being arranged in described filling compartment and described filling channel.

20. box as claimed in claim 15, described filling compartment is limited by the well formed at least one in described first and second walls of described packing at least in part.

21. box as claimed in claim 15, further comprise fill system, it is configured to be communicated with described filling compartment by fluid seal.

22. box as claimed in claim 15, it is the first wall along described the first compartment that wherein said filling channel is formed the guiding of the fluid of described fluid dose package, to prevent injection.

23. box as claimed in claim 15, further comprise the gas discharge side be communicated with described the first compartment via the fluid expulsion passage, described fluid expulsion passage is salable to stop flowing from described the first compartment after filling.

24. box as claimed in claim 1, at least a portion of wherein said packing comprises tubular structure.

25. box as claimed in claim 1, further comprise obturator, it is always isolated by described the first compartment and described adnexa before being opened.

26. one kind for having the aseptic box of the useful drug delivery device that can fill reservoir, described box comprises:

Packing, it comprises:

At least the first compartment of at least one component that comprises described useful medicament, described packing is limited by preformed flexible wall at least in part; With

Be arranged in the adnexa on described packing, for by described packing with described fill reservoir join and fluid be communicated with.

27. box as claimed in claim 26, wherein said packing comprises described the first compartment and the second compartment, the second component that the first component that described the first compartment comprises described useful medicament and described the second compartment comprise described useful medicament, described the second compartment is isolated by obstruct and described first compartment that can ftracture.

28. box as claimed in claim 26, at least a portion of wherein said flexible wall comprises paillon foil or film.

29. box as claimed in claim 26, at least a portion of wherein said flexible wall comprises peelable foil layer.

30. box as claimed in claim 29, at least a portion of wherein said peelable foil layer is preformed.

31. box as claimed in claim 26, further be included in the fluid passage of extending between described the first and second compartments.

32. box as claimed in claim 31, further comprise the static mixer be arranged in described fluid passage.

33. box as claimed in claim 26, further comprise the fluid passage between described packing and described delivery apparatus, and be arranged in the static mixer in described fluid passage.

34. box as claimed in claim 26, wherein said packing comprises flexible wall, and described flexible wall extends to form at least a portion of the aseptic cover of described adnexa.

35. box as claimed in claim 26 further comprises and fills compartment, fluid filled passage and the first and second package wall that described filling compartment is communicated with described the first compartment fluid via described fluid filled passage.

36. box as claimed in claim 35, wherein said filling compartment is between described the first and second package wall.

37. box as claimed in claim 35, wherein said fluid passage is sealable to stop during filling or to flow to the backflow of described filling compartment after filling.

38. box as claimed in claim 35, wherein said fluid filled passage seals by the heat seal between described the first and second package wall.

39. box as claimed in claim 35, further comprise the isolating valve at least one being arranged in described filling compartment and described fluid filled passage.

40. box as claimed in claim 35, wherein said fluid filled compartment is limited by the well formed at least one in described the first and second package wall at least in part.

41. box as claimed in claim 35, further comprise fill system, it is configured to be communicated with described filling compartment by fluid seal.

42. box as claimed in claim 35, the fluid that wherein said filling channel guides described packing to hold along the first package wall, to prevent injection.

43. box as claimed in claim 35, further comprise the gas discharge side, described gas discharge side is communicated with described the first compartment via sealable fluid expulsion passage, to stop flowing from described the first compartment after filling.

44. box as claimed in claim 26, further comprise obturator, it is always isolated by described the first compartment and described adnexa before being opened.

45. one kind for having the box of the useful drug delivery device that can fill reservoir, described box comprises:

Backing; With

Package component comprises:

At least the first compartment of at least one component that comprises described useful medicament, described the first compartment is limited by flexible wall at least in part; With

46. box as claimed in claim 45, wherein said box is connected via described backing with described delivery apparatus.

47. box as claimed in claim 45, wherein said backing comprises the fluid passage of described box and the interconnection of described delivery apparatus.

48. box as claimed in claim 47, wherein said fluid passage is by sterile sealing.

49. box as claimed in claim 47, wherein said fluid passage comprises obturator, and this obturator was separated described packing compartment and described reservoir before being opened always.

50. box as claimed in claim 45, further be included in the obstruct of ftractureing between described the first compartment and described adnexa.

51. box as claimed in claim 45, wherein said package component comprises at least the second compartment, at least second component that this at least the second compartment comprises described useful medicament, and described the second compartment is separated by obstruct and described first compartment that can ftracture.

52. box as claimed in claim 45, at least a portion of wherein said flexible wall comprises paillon foil.

53. box as claimed in claim 52, wherein said flexible wall preform is to limit at least a portion of described the first compartment.

54. box as claimed in claim 45, at least a portion of wherein said flexible wall comprises peelable foil layer.

55. box as claimed in claim 54, at least a portion of wherein said peelable foil layer is preformed.

56. box as claimed in claim 45, further comprise the fluid passage be positioned between described the first and second compartments.

57. box as claimed in claim 56, further comprise the static mixer be arranged in described fluid passage.

58. box as claimed in claim 54, further comprise the static mixer be arranged in fluid passage, this fluid passage is positioned between described package component and described delivery apparatus.

59. box as claimed in claim 45, wherein said flexible wall extends to form at least a portion of the aseptic cover of described adnexa.

60. box as claimed in claim 45 further comprises and fills compartment, fluid filled passage and the first and second package wall that described filling compartment is arranged to be communicated with described the first compartment fluid via described fluid filled passage.

61. box as claimed in claim 60, wherein said filling compartment is between described the first and second package wall.

62. box as claimed in claim 60, wherein said fluid passage is salable to stop the backflow that flows to described filling compartment after filling.

63. box as claimed in claim 60, wherein said fluid passage seals by the heat seal between described the first and second package wall.

64. box as claimed in claim 15, further comprise the isolating valve at least one being arranged in described filling compartment and described filling channel.

65. box as claimed in claim 15, wherein said filling compartment is limited by the well formed at least one in described the first and second package wall at least in part.

66. box as claimed in claim 60, further comprise fill system, it is configured to be communicated with described filling compartment via fluid seal.

67. box as claimed in claim 60, the fluid that wherein said filling channel guides described packing to hold along the first package wall, to prevent injection.

68. box as claimed in claim 60, further comprise the gas discharge side be communicated with described the first compartment via the fluid expulsion passage, described fluid expulsion passage is sealable to stop flowing from described the first compartment after filling.

69. box as claimed in claim 45, wherein said delivery apparatus is selected from: injector for medical purpose, give as security needle injection, safety injector, contraction type needle applicator, automatically forbid syringe, automatic injector, ejector filler, intradermal syringe, hypodermic syringe, intramuscular injection device, transfusion device, infusion pump, slow release delivery system and attach pump.

70. one kind for having the box of the useful drug delivery device that can fill reservoir, described box comprises:

Packing, it comprises:

At least the first compartment of at least one component that comprises described useful medicament;

Be arranged in the adnexa on described packing; With

Be connected to the coupler of described adnexa, for by described packing with described fill reservoir join and fluid be communicated with.

71. box as described as claim 70, wherein said coupler comprises obturator, and described obturator interrupted described fluid always and is communicated with before being opened.

72. box as described as claim 70, wherein said coupler is by sterile sealing.

73. box as described as claim 70, wherein said coupler comprises the injection needle that can join with described delivery apparatus.

74. box as described as claim 73, wherein said coupler comprises interrupts the barrier film that described fluid is communicated with, and the end of described injection needle can puncture described barrier film.

75. box as described as claim 74, wherein said injection needle can move to the second position from primary importance, states barrier film in described primary importance place and is not punctured, and states barrier film in described second position place and is punctured.

76. box as described as claim 70, wherein said coupler is configured to be communicated with doser.

77. box as described as claim 70, wherein said coupler comprises the mobile valve of controlling the described packing of turnover.

78. box as described as claim 77, wherein said valve can operate by the relative motion between described adnexa and described coupler.

79. box as described as claim 70, wherein, after described useful medicament is filled described reservoir at least in part, at least a portion of described packing can be from described coupler dismounting.

80. box as described as claim 70, wherein, described coupler comprises safety device, and described safety device is selected from and prevents the device that syringe needle jabs and prevent the device re-used, and when the part of described box removes from described delivery apparatus, described safety device and described delivery apparatus link.

81. box as described as claim 70, further comprise the backing for described packing.

82. box as described as claim 70, wherein said coupler is configured to the cap of described delivery apparatus.

83. box as described as claim 70, wherein said delivery apparatus is selected from injector for medical purpose, signature needle injection, safety injector, contraction type needle applicator, automatically forbids syringe, automatic injector, ejector filler, intradermal syringe, hypodermic syringe, intramuscular injection device, transfusion device, infusion pump, slow release delivery system and attach pump.

84. box as described as claim 70, wherein said coupler comprises at least a portion of syringe piston.

85. box as described as claim 70, wherein said coupler comprises at least a portion of syringe sleeve.

86. box as described as claim 70, wherein said coupler and adnexa are by least one connection in interference fit, thermal welding and bonding.

87. box as described as claim 70, wherein said coupler is configured to be communicated with the syringe of the delivery apparatus that comprises syringe needle, and is configured to when described packing connects with described syringe and described adnexa links.

88. coupler as described as claim 87, wherein said delivery apparatus comprises needle protector, and described needle protector can remove when described packing and syringe connection.

89. coupler as described as claim 87, wherein said delivery apparatus comprises the aseptic cover for described syringe needle, and this aseptic cover is held until described packing and syringe connect always.

90. coupler as described as claim 87, wherein said coupler is configured to medially disposed therein.

91. coupler as described as claim 87, further comprise the obturator in the endoporus that is arranged in described coupler, described coupler can move axially between the near-end of the far-end of described syringe needle and described syringe needle.

92. box as described as claim 87, wherein, when described box removes from described syringe, described coupler keeps linking with described adnexa.

93. coupler as described as claim 70, further comprise the fluid passage be communicated with for fluid between described packing and described reservoir, described fluid passage ends at barrier film, and this barrier film can be punctured by injection needle.

94. box as described as claim 70, wherein said packing comprises at least one flexible wall, and this at least one flexible wall preform is to limit at least a portion of described the first compartment.

95. box as described as claim 70, wherein said packing comprises at least one flexible wall, and this at least one flexible wall has peelable foil layer part.

96. box as described as claim 95, at least a portion of wherein said peelable foil layer is preformed.

97. box as described as claim 70, further comprise in the first compartment of described packing and the fluid passage between the second compartment.

98. box as claimed in claim 28, further comprise the static mixer be arranged in described fluid passage.

99. box as described as claim 70, further comprise the fluid passage be positioned between described packing and described delivery apparatus, and be arranged in the static mixer in described fluid passage.

100. box as described as claim 70, wherein said packing further comprises flexible wall, and this flexible wall extends to form at least a portion of the aseptic cover of described adnexa.

101. box as described as claim 70 further comprises and fills compartment, fluid filled passage and the first and second package wall that described filling compartment is arranged to be communicated with described the first compartment fluid via described fluid filled passage.

102. box as described as claim 101, wherein said filling compartment is positioned between described first and second package wall.

103. box as described as claim 101, wherein said fluid passage is sealable to stop the backflow that flows to described filling compartment after filling.

104. box as described as claim 101, wherein said fluid passage seals by the heat seal between described the first and second package wall.

105. box as described as claim 101, further comprise the isolating valve at least one being arranged in described filling compartment and described filling channel.

106. box as described as claim 101, wherein said filling compartment is limited by the well formed at least one in described the first and second package wall at least in part.

107. box as described as claim 101, further comprise fill system, this fill system is configured to be communicated with described filling compartment by fluid seal.

108. box as described as claim 101, the fluid that wherein said filling channel guides described packing to hold along the first package wall, to prevent injection.

109. box as described as claim 101, further comprise the gas discharge side be communicated with described the first compartment via the fluid expulsion passage, described fluid expulsion passage is sealable to stop flowing from described the first compartment after filling.

110. one kind for having the box of the useful drug delivery device that can fill reservoir, described box comprises:

Unit dose packaging, all components that it comprises the whole of described useful medicament or comprises described useful medicament, this unit dose packaging comprises:

At least the first compartment of at least one component that comprises the whole of described useful medicament or comprise described useful medicament, described the first compartment is limited by flexible wall at least in part; With

Be arranged in the adnexa on described packing, for described packing is filled to reservoir joins and fluid is communicated with described.

111. a pre-filled cap, for sealing the administration part of the useful drug delivery device of the unit dose that comprises the monoblock type reservoir, described pre-filled cap comprises:

At least the first compartment of at least one component that comprises described useful medicament; With

Fluid passage, partly be communicated with described administration for making described the first compartment.

112. pre-filled cap as described as claim 112, wherein said the first compartment comprises wall, and at least a portion of described wall comprises flexible material.

113. pre-filled cap as described as claim 113, wherein said flexible material comprises film.

114. pre-filled cap as described as claim 112, the first component that wherein said the first compartment comprises described useful medicament, and described pre-filled cap further comprises the second compartment of the second component that comprises described useful medicament, also comprise the openable obturator that described the first and second components are separated.

115. pre-filled cap as described as claim 112, wherein said administration partly comprises with lower a kind of: syringe needle, conduit, adapter, Rule adapter, nozzle, ejector filler nozzle, dispenser, miniature syringe needle, ID syringe needle, IM syringe needle and SQ syringe needle.

116. pre-filled cap as described as claim 112, further comprise obturator, described obturator separates described compartment and described administration part until described obturator is opened.

117. pre-filled cap as described as claim 112, further comprise fluid passage.

118. pre-filled cap as described as claim 112, further comprise the barrier film that seals described fluid passage.

119. pre-filled cap as described as claim 118, wherein said administration partly comprises syringe needle, thereby described syringe needle is removable, to puncture described barrier film foundation, with the fluid of described fluid passage, is communicated with.

120. pre-filled cap as described as claim 118, wherein said administration partly comprises syringe needle, and described syringe needle is configured to puncture described barrier film and is communicated with the fluid of described fluid passage to set up.

121. pre-filled cap as described as claim 112, further comprise the backing for described the first compartment.

122. pre-filled cap as described as claim 112, wherein said the first compartment is formed in the packing that comprises adnexa.

123. pre-filled cap as described as claim 122, at least a portion of wherein said packing comprises film.

124. a useful medicament unit dose dispenser comprises:

Delivery apparatus, have the unit dose reservoir that can fill and fill with described at least one port that reservoir is communicated with; With

Box, it sterilely is connected to described delivery apparatus, and described box comprises:

Unit dose packaging comprises:

At least the first compartment of at least one component that comprises described useful medicament, described packing is limited by flexible wall at least in part; With

Adnexa, link with described unit dose packaging and described unit dose packaging and described delivery apparatus joined; With

Openable sealing member, be arranged between described the first compartment and described reservoir.

125. dispenser as described as claim 124, wherein described reservoir is basic overhead before use.

126. dispenser as described as claim 124, at least one component that wherein said reservoir comprises described useful medicament.

127. one kind for distributing the pre-filled syringe of useful medicament, comprising:

Piston component;

The sleeve that can fill, it comprises the administration part; With

Pre-filled box, it comprises at least the first compartment of at least the first component that comprises described useful medicament, and the flow channel be communicated with described sleeve for the content that makes described the first compartment.

128. pre-filled syringe as described as claim 127, wherein said administration partly comprises with lower a kind of: syringe needle, IM syringe needle, miniature syringe needle, ID syringe needle, SQ syringe needle, safety needle, contraction type syringe needle, nozzle, injection injection nozzle, dispenser and applicator.

129. pre-filled syringe as described as claim 127, further comprise the described administration of sealing cap partly, described box and described cap are integrally formed.

130. pre-filled syringe as described as claim 127, further comprise flow channel, this flow channel is communicated with described sleeve via described administration part.

131. pre-filled syringe as described as claim 127, at least second component that wherein said sleeve comprises described useful medicament.

132. pre-filled syringe as described as claim 127, further comprise obturator, described obturator is separated described the first compartment and described sleeve, until described obturator is opened.

133. pre-filled syringe as described as claim 127, wherein said pre-filled syringe is disposed for manual operation.

134. pre-filled syringe as described as claim 127, wherein said pre-filled syringe is configured at least one operation in automatic injector, syringe pump, controlled actuators, mechanical plunger or mechanical pressure.

135. pre-filled syringe as described as claim 127, the near-end of wherein said sleeve is by sterile sealing.

136. the cap of the part of the administration for delivery apparatus, described cap comprises fluid passage, is configured to and the partially communicating near-end of described administration, and far-end.

137. cap as described as claim 136, further comprise jointer, this jointer is positioned in the far-end of described fluid passage, with the packing for pre-filled, is communicated with.

138. cap as described as claim 137, wherein said jointer is configured to be communicated with the adnexa of described pre-filled packing.

139. cap as described as claim 136, further comprise obturator, described obturator is arranged in described fluid passage, and is configured to the described far-end of described fluid passage and described near-end are separated, until described obturator is opened.

140. cap as described as claim 136, wherein said cap is configured to seal described administration part.

141. cap as described as claim 136, wherein said cap is configured to partly provide mechanical protection to described administration.

142. cap as described as claim 136, further comprise backing, to support pre-filled packing.

143. a method that is used to form the pre-filled packing of useful medicament comprises:

Film with the first side and second side is provided, and this first side, with together with the second side is connected to, is formed on the border of at least the first component compartment between them;

At least a portion along described border forms frangible;

Form sealed-for-life, make at least some of the overlapping described frangible of described sealed-for-life, with generation, there is the overlapping part with the essentially identical sealing characteristics of described sealed-for-life; With

Fill described the first component compartment.

144. method as described as claim 143, wherein said frangible forms along whole border.

145. method as described as claim 143, further be included in the described frangible of formation and fill described the first component compartment by least described first component of described useful medicament before.

146. method as described as claim 143, wherein, after forming described frangible and before forming described sealed-for-life, described the first component compartment is filled by least the first component of described useful medicament.

147. method as described as claim 146, further is included as described the first component compartment and forms filling vias, and wherein said sealed-for-life seals described filling vias.

148. method as described as claim 143, wherein said frangible shows the first peel strength characteristic, and described sealed-for-life shows the second peel strength characteristic, the sealing setting of the water-tight equipment of described the first and second peel strength characteristics by being used to form frangible and sealed-for-life obtains.

149. method as described as claim 143, wherein said frangible presents the first peel strength characteristic, and described sealed-for-life presents the second peel strength characteristic, and described the first peel strength characteristic is caused by the partially sealed characteristic of described film.

150. method as described as claim 143, the major part of the overlapping described frangible of wherein said the second sealing.

151. method as described as claim 143, wherein said border limits at least the second compartment, and wherein after described sealed-for-life forms the frangible section be retained between described the first and second compartments.

152. a method that forms the pre-filled packing of useful medicament comprises:

The gas that is formed for described useful medicament is filled compartment;

Formation has the filling compartment of fill port, and this fill port is filled compartment via the first salable channel and described gas and is communicated with;

Formation has the emptying compartment of port, and this port of emptying compartment is filled compartment via the second salable channel and described gas and is communicated with;

In a fluid tight manner the source of at least the first component of described useful medicament is coupled mutually with described fill port;

Fill described gas via described filling channel from described source and fill compartment, simultaneously by described emptying port Exhaust Gas; With

Seal the described first salable channel and described filling channel.

153. method as described as claim 152, further comprise and prune described pre-filled packing, to remove described port.

154. method as described as claim 152, at least a portion of wherein said pre-filled packing comprises film.

155. method as described as claim 154, wherein, described film preform is filled the volume of compartment to limit described gas.

156. method as described as claim 155, wherein during filling, described pre-filled pack is contained in chamber, fills the volume of compartment further accurately to limit described gas.

157. method as described as claim 156, wherein apply vacuum to described chamber.

158. method as described as claim 157, wherein, during filling, described pre-filled packing is positioned such that emptying channel raises with respect to described filling channel.

159. method as described as claim 152, wherein said fill port comprises well.

160. method as described as claim 152, wherein with the interface arrangement in the source of described the first component in described fill port.

161. method as described as claim 160, wherein said interface comprises valve.

162. method as described as claim 152, before the sealing step, described compartment and described channel are with respect to the environment gas-tight seal.

163. method as described as claim 162, wherein, before filling step, the wall of described fill port is punctured to receive the source of described the first component.

164. method as described as claim 163, the source of wherein said the first component comprises and ends at the capillary tube that pierces through element.

165. method as described as claim 164, wherein said capillary tube punctures the thin slice wall of described fill port, and described thin slice and described capillary tube form fluid-tight.

166. method as described as claim 162, further comprise stacking a plurality of described pre-filled packing, and stacking packing be transported to filling machine.

167. method as described as claim 152, at least one in wherein said the first sealing channel and described filling channel comprises sealable plug-in unit.

168. method as described as claim 152, wherein said filling channel is manufactured into, and makes during filling step, and described component flows to prevent injection, foaming or bubble along the wall of described compartment.

169. method as described as claim 152, further comprise the sensor of the existence that is provided for detecting the described component in described emptying channel, and indicate described compartment to be filled with described sensor.

170. method as described as claim 152, the source of wherein said the first component comprises dosing pump.

171. method as described as claim 170, the source of wherein said the first component comprises non-metering pumping system.

172. method as described as claim 152, further comprise for receiving by the vent line of described emptying port expellant gas.

173. method as described as claim 152, further be included in described emptying port and apply vacuum.

174. method as described as claim 152, wherein said component comprises and is selected from following solid matter: powder, spherolite, granule, tablet, group, ball and tiny balls.

175. method as described as claim 174, wherein, during filling step, be transported to compartment with air-flow by described component.

176. method as described as claim 175, the size of at least one opening of wherein said emptying channel prevents that described component from arriving described emptying port.

177. method as described as claim 175, wherein said pre-filled being packaged on shaping-filling-sealing production line manufactured.

178. method as described as claim 152, wherein a plurality of described pre-filled packings are manufactured by the single sheet member.

179. method as described as claim 152, wherein used vacuum that the source of described the first component is attached to described fill port.

180. a manufacture is used for the method for the unit dose delivery apparatus of useful medicament, comprising:

Receive the delivery apparatus of assembling;

Receive the box of pre-filled sterile sealing, described box is by least the first component of pre-filled described useful medicament; With

Box in conjunction with described delivery apparatus and described sterile sealing.

181. method as described as claim 180, wherein said delivery apparatus is syringe, and this syringe comprises the pre-assembled piston to sleeve.

182. method as described as claim 180, wherein said delivery apparatus and box are pre-sterilized, and the method further comprises sterilely in conjunction with described delivery apparatus and described box.

183. method as described as claim 180, further be included in conjunction with the most described delivery apparatus sterilizing afterwards.

184. the method for the useful medicament packing of the unit dose by liquid condition comprises:

In mould, that the described useful medicament of measurement unit dosage is freezing to produce cryodose;

Described cryodose is put in half-done compartment; With

Seal described compartment.

185. method as described as claim 184, wherein said packing comprises blister pack, and described cryodose is put into preformed chamber thus.

186. method as described as claim 184, before further being included in and putting in described compartment by described cryodose, check described cryodose at least one controlled characteristic.

187. method as described as claim 184, further comprise by least the first sheeting and manufacture described packing, and described unit dose is chilled on described sheeting.

188. method as described as claim 184, further be included in the sealing described cryodose that thaws after described compartment.

189. method as described as claim 184, further be included in the described compartment of sealing and before described cryodose be exposed to and be enough to prevent the temperature of thawing.

190. the method for the dosing packing of at least the first component of the useful medicament by the charge of flowable solids material forms comprises:

Measure the dosage of described the first component;

Compress the dosage of described metering, thereby be enough to form unitary body;

Described unitary body is put in half-done packing;

Seal described packing; With

Wall by described packing is directed to described monoblock type dosage by energy, so that described monoblock type dosage is transformed into to shot.

191. method as described as claim 190, further be included in to put into before described packing and check described unitary body at least one controlled characteristic.

192. method as described as claim 190, wherein said packing is made by least the first thin slice at least in part, and further comprises described dosage is compressed on described thin slice.

193. method as described as claim 190, further be included on shaping-filling-sealing production line and form described packing.

194. method as described as claim 190, at least a portion of wherein said packing comprises sheeting, and further comprises, wherein the flexible wall by described packing presses down described unitary body and guides described energy.

195. method as described as claim 190, at least one in wherein vibrating by mechanical vibration, supersonic vibration, audio frequency vibration and RF is directed to described monoblock type dosage by described energy.