CN103813811A

CN103813811A - Fluid sterilant injection sterilization device and method

Info

Publication number: CN103813811A
Application number: CN201280040640.4A
Authority: CN
Inventors: 丹尼尔·皮
Original assignee: Individual
Current assignee: Individual
Priority date: 2011-06-21
Filing date: 2012-06-21
Publication date: 2014-05-21
Also published as: CN108619536A; EP2723395B1; WO2012177933A1; US20130008137A1; EP2723395A4; HK1198245A1; EP2723395A1; BR112013033307A2

Abstract

A method for sterilizing a container is provided where a penetrable septum of a sealed empty device is penetrated with an injection member. A fluid sterilant is then injected through the injection member and into an interior chamber of the device. The fluid sterilant is allowed to reside within the chamber a sufficient amount of time to render the chamber either sterile or bactericidal. Product can then be introduced through the septum into the sterile or bactericidal chamber. The resulting penetration aperture is then resealed to hermetically seal the product within the chamber.

Description

Fluid sterilization agent injection bactericidal unit and method

The cross reference of related application

It is that " NITRIC OXIDE INJECTION STERILIZATION DEVICE AND METHOD ", serial number are 61/499 that present patent application requires in the title that on June 21st, 2011 submits to, rights and interests under 626 U.S. Provisional Application 35U.S.C. § 119 (e), at this, it is incorporated to by reference clearly, using the part as present disclosure.

Technical field

The application relates to the sterilizing of sealing empty, and more specifically, relates to by injecting nitric oxide gas or other fluid sterilization agent to the sterilizing of sealing empty in container.

Background technology

Often, manufacture container and hold the aseptic sensitive product of necessary maintenance, thereby avoid any antibacterial or microorganism to grow therein.With product and other types product, be often this situation for medicine, food, nutriment, eye.Therefore, before product filled, must carry out sterilizing to these containers.Set up prior art systems and carried out such task, still, these systems may be not integral asepsis always, but may make container be exposed to momently non-sterile material, for example air.On the other hand, some prior art systems can produce the environment of integral asepsis, but implement conventionally too expensive.Other prior art systems utilize gamma-radiation to sterilizing containers.The shortcoming of this method is that gamma-radiation can be used in the material damage or the decomposition that produce container, the closure (closure) of container or the sealing of closure.

An object of the present invention is to overcome one or more shortcoming and/or the drawback of prior art.

Summary of the invention

According to first aspect, method comprises the following steps:

(i) utilize injection member (injection member) to penetrate the penetrable barrier (penetrable septum) of the empty device of sealing (device);

(ii) fluid sterilization agent (fluid sterilant) is incorporated in the interior chamber (interior chamber) of described device by injection member;

(iii) allow described fluid sterilization agent in described chamber, to stop the time of q.s so that described chamber is at least substantially aseptic or sterilization substantially;

(iv) utilize injection or filling element penetrate described penetrable barrier, by described injection or filling element by product be incorporated into described aseptic or sterilization chamber in; And

(v) perforation (penetration aperture) that sealing produces again, to be thickly sealed in described gas product in described chamber.

In some embodiments, step (i) and (ii) carry out at fluid sterilization agent station (station), step (iii) is carried out at biocide docking station, step (iv) at filling station or product injection station carry out, step (v) is carried out sealing station again, and also carry out in curing station in some embodiments.

In one embodiment, described method removes the agent of (withdraw) fluid sterilization before being also included in product being incorporated in chamber from chamber.In some such embodiments, remove step and comprise that the device by inserting through penetrable barrier carrys out evacuation.In some embodiments, removing in find time station or vacuum station of fluid sterilization agent carried out.In other embodiments, it carries out at filling station.

In some embodiments, the device inserting through penetrable barrier is pin.In some embodiments of the present invention, fluid sterilization agent is nitric oxide or other hydroxyl radical gas (free radical gas).

Some embodiments are also included in step (iv) and before the penetrable surface of barrier are carried out to sterilizing or decontamination (decontaminating).Some such embodiments are also included in step (i) and before the penetrable surface of barrier are carried out to sterilizing or decontamination.In some embodiments, the sterilizing to penetrable surface or decontamination comprise penetrable surface are applied to fluid sterilization agent or radiation.In some embodiments, fluid sterilization agent is hydrogen peroxide (the vaporized hydrogen peroxide of vaporization, " VHP "), radiation is ultraviolet (ultraviolet, " UV "), gamma-rays, β ray or electron beam (e-beam).

Some embodiments be also included in step (iv) and (v) during introduce filtrated air or other gas of superpressure (overpressure).Some such embodiments be also included in step (i) and (ii) during introduce filtrated air or other gas of superpressure.

In some embodiments, then seal step and comprise to produced perforation and apply fluid sealant.In some such embodiments, then seal step and also comprise to fluid sealant and apply radiation or energy so that fluid sealant is solidified into solid phase from liquid phase.In some such embodiments, radiation is UV radiation, for example high energy pulse UV radiation.In other embodiments of the present invention, barrier can be by applying radiation to it or energy seals again, then seal step and be included in produced perforation place and apply radiation or energy and the heat that makes to bore a hole seals (thermally resealing) again to barrier.In other embodiments, barrier can heat seal again, and radiation or energy are laser or heat radiation or energy.

According to another aspect, equipment (apparatus) comprises:

(i) device, the empty chamber that it comprises sealing and the penetrable barrier being communicated with described chamber; With

(ii) the fluid sterilization agent source being communicated with injection member, described injection member is used for by described injection member, fluid sterilization agent being incorporated into the chamber of described device, and allows described fluid sterilization agent in described chamber, to stop the time of q.s so that described chamber is aseptic or sterilization.

In some embodiments of the present invention, described equipment also comprises product source, in described product chamber to be loaded into, and described product source is connected communicatively with injection or filling element fluid, described injection or filling element are used for utilizing injection or filling element to penetrate penetrable barrier and by injection member, product is incorporated into described chamber.Some such embodiments also comprise sealing station again, and it is for sealing the perforation producing so that gas product is thickly sealed in to chamber again.In some such embodiments, then sealing station comprises fluid sealant source, and it also seals described barrier again for metering liquid sealant in the perforation to produced.In some such embodiments, then sealing station comprises radiation or energy source, its for transmission (transmit) radiation or energy on fluid sealant so that sealant is solidified into solid phase from liquid phase.In other embodiments of the present invention, then sealing station comprise radiation or energy source, it applies radiation or energy and the perforation that can for example, seal again by radiation or energy (laser emission) is sealed again to barrier for perforation place produced.

According to another aspect, the present invention relates to a kind of equipment, it comprises:

(ii) first component (means), it is for penetrating penetrable barrier and by penetrable barrier, fluid sterilization agent being incorporated into the chamber of described device, and allows fluid sterilization agent in chamber, to stop the time of q.s so that described chamber is at least substantially aseptic or sterilization substantially.

Some embodiments also comprise for penetrating penetrable barrier and by penetrable barrier, product being incorporated into the second component of chamber.Some embodiments also comprise the 3rd parts for the perforation that sealing produces again.Some embodiments also comprise for the 4th parts using first component or second component the penetrable surface of barrier to be carried out to sterilizing or decontamination before penetrating barrier.In some embodiments, first component is injection member and the fluid sterilization agent source that is connected communicatively with injection member fluid; Second component is injection or filling element and the product source being connected communicatively with described injection or filling element fluid; The 3rd parts are fluid sealant or radiation; And the 4th parts are fluid sterilization agent or radiation.

In some embodiments, for the injection member of fluid sterilization agent, for the device of evacuation and/or can be same for injection or the filling element of product, and as an alternative, described element or device can be connected with biocide source, vacuum source and product source.In some embodiments, fluid sterilization agent station or module, biocide docking station or module, station or the vacuum station of finding time or module, filling station or module, again seal in station or module and/or curing station or module one or more of combined with make can be at single station or module exceed the described process of.

An advantage of the present invention is that the fluid sterilization agent of injection makes inside sterilizing or the decontamination of device, thereby has avoided using necessity of gamma-radiation or other prior art sterilizings and/or decontaminating apparatus and method.And another advantage be can be before facing filling and with the sterilizing in same facility or uniform machinery of described device.

By the following detailed description of at present preferred embodiment and accompanying drawing, other objects and advantages of the present invention and/or its at present more preferred embodiments will become more obvious.

Accompanying drawing summary

Fig. 1 is for sealing empty is carried out to sterilizing the schematic diagram with backward sterile chamber product filled the sterilizing that container is sealed again and loading system; With

Fig. 2 is the schematic diagram that another sterilizing and loading system are shown.

The detailed description of embodiment of the present invention

In Fig. 1, show the schematic diagram for sealing empty being carried out to the disinfection system of sterilizing.Described disinfection system comprises multiple stations, and described station comprises fluid sterilization agent injection station 14, biocide docking station 16, product injection station 18, sealing station 20 and curing station 22 again.Multiple fan/filter assemblies (assembly) 24 are installed communicatively with described station fluid, and filtrated air or other gas of superpressure is optionally provided in each station.Can before disinfection system, build station with manufacturing installation 10 by generator.

Manufacturing installation 10 in the complete molding station 12 shown in Fig. 2 or device structure station, therefore, in some embodiments, form by co-molded (co-molding) or secondary molding (over-molding) snap ring (snap-ring) that comprises check valve.In some embodiments that comprise snap ring, secondary molding valve gap (valve cover) on valve body, and abreast, injection-molded (injection molded) preform (pre-form) and and then blowing with form pouch (pouch).Can be according to disclosed device in following application and manufacture method construction device 10: the common unsettled U. S. application No.11/804 that the title of submitting to May 18 in 2007 is " Delivery Device with Separate Medicament and Beverage Chambers Connectable in Fluid Communication When Ready for Use.and Related Method ", 431, described application requirement is in the U.S. Provisional Application No.60/801 of the similar title of submission on May 18th, 2006,978 priority; The title of submitting on October 9th, 2009 is the common unsettled U. S. application No.12/577 of " Co-Extrusion Blow Molding Apparatus and Method; and Sealed Empty Devices ", 104, described application requirement is in the U.S. Provisional Application No.61/104 of the similar title of submission on October 10th, 2008,649 priority; The title of submitting on October 9th, 2009 is the common unsettled U. S. application No.12/577 of " Device with Co-Extruded Body and Flexible Inner Bladder and Related Apparatus and Method ", 126, described application requirement is in the U.S. Provisional Application No.61/104 of the similar title of submission on October 10th, 2008,613 priority; And the title of submitting on October 8th, 2010 is the common unsettled U. S. application No.12/901 of " Device with Co-Molded Closure; One-Way Valve and Variable-Volume Storage Chamber and Related Method ", 420, the title that described application requirement was submitted on October 9th, 2010 is the U.S. Provisional Application No.61/250 of " Device with Co-Molded One-Way Valve and Variable-Volume Storage Chamber and Related Method ", 363 priority; At this, each of these applications is all incorporated to by reference clearly, using the part as present disclosure, as fully provided in this article.Apparatus main body 26 also with closure 28 (for example above-mentioned snap ring/valve gap) and other assemblies molding abreast of apparatus main body 26.In the time that all component completes, automaton (robotic machine) is assembled to pouch to form the empty device 10 of sealing by snap ring and valve combination.Then the empty device 10 of fitting tight before can and/or loading in sterilizing.In the time assembling completely, each device 10 is emptys of sealing, the closed chamber 30 in closure 28 and the main body 26 of its opening that comprises main body 26, sealed body.

After assembling completely, device 10 is transferred to fluid sterilization agent injection station 14.At this station, can for example, carry out sterilizing to the penetrable surface (surface of closure 28) of device as electron beam, gamma-radiation or β radiation by for example applying ultraviolet radiation or the sterilizing by any other form as known in the art to it.In some embodiments, outer surface and penetrable surface are carried out further sterilizing.Then, pin 32 or other injection member are inserted and penetrate closure 28.Thereby in the time penetrating closure 28 with pin 32 pin 32 or pin hole are communicated with closed chamber 30 fluids of main body 26, by pin 32, fluid sterilization agent (for example nitric oxide gas (NO)) is expelled to the inside of closed chamber 30.For example, after in biocide (NO) is incorporated into chamber 30, can remove pin 32.The fluid sterilization agent using is not limited to NO, and can be any suitable biocide as known in the art, comprises vaporized hydrogen peroxide (" VHP ").

Can come generator 10, fluid sterilization agent injection station 14, closure 28, pin 32 etc. according to the instruction of following application: the U. S. application No.61/659 that the title of submitting on June 13rd, 2012 is " Device with Penetrable Septum; Filling Needle and Penetrable Closure; and Related Method ", 382; The title of submitting on April 18th, 2012 is the U. S. application No.13/450 of " Needle With Closure and Method ", 306, it is the U.S. Provisional Application No.61/476 of " Filling Needle and Method " that described application requirement is submitted title on April 18th, 2011,523 rights and interests; The title of submitting on April 18th, 2011 is the U. S. application No.61/635 of " Self Closing Connector ", 258; And/or be the U. S. application No.61/625 of " Self Closing Connector " in the title of submission on April 17th, 2012,663; At this, these applications are incorporated to by reference clearly, using the part as present disclosure, as fully provided in this article.It should also be understood that the above application of enumerating is not limited to those elements of previously having enumerated, but can any pin or injection member, injection station are provided or relate to the station injecting a fluid in device 10 according to these applications.

Or, can carry out generator 10 according to the instruction of following patent and common pending application application: the title of authorizing on April 25th, 2006 is " Medicament Vial Having a Heat-sealable Cap, and Apparatus and Method for Filling the Vial " U.S. Patent No. 7, 032, 631, described patent is the U.S. Patent No. 6 of the similar title authorized on October 19th, 2004, 805, 170 part continuation application, the latter is the U.S. Patent No. 6 of authorizing on February 3rd, 2004, 684, 916 continuation application, U.S. Patent No. 6, 684, the 916th, the U.S. Patent No. 6 of the similar title of authorizing on August 12nd, 2003, 604, 561 division, No.6, 604, it is No.60/182 that 561 United States Patent (USP)s require again in the serial number of the similar title of submission on February 11st, 2000, the priority of 139 U.S. Provisional Application, and require in the U.S. Provisional Patent Application No.60/442 of the similar title of submission on January 28th, 2003, 526 and the U.S. Provisional Patent Application No.60/484 of similar title that submits on June 30th, 2003, 204 priority,

The U.S. Patent No. 7 that the title of authorizing for 5th in JIUYUE in 2006 is " Sealed Containers and Methods of Making and Filling Same ", 100, 646, described patent is that the title of authorizing on February 3rd, 2004 is " Medicament Vial Having a Heat-sealable Cap, and Apparatus and Method for Filling the Vial " U.S. Patent No. 6, 684, 916 part continuation application, the latter is the U.S. Patent No. 6 of the similar title authorized on August 12nd, 2003, 604, 561 division, U.S. Patent No. 6, 604, 561 to require again the serial number of similar title of submitting on February 11st, 2000 be No.60/182, the priority of 139 U.S. Provisional Application, and the title that requires to submit to for 3rd in JIUYUE in 2002 the U.S. Provisional Patent Application No.60/408 that is " Sealed Containers And Methods Of Making And Filling Same ", 068 priority, and be the common unsettled U.S. Provisional Application No.61/476 of " Filling Needle and Method " in the title of submission on April 18th, 2011,523, at this, each of these applications is all incorporated to by reference clearly, using the part as present disclosure, as fully provided in this article.

For example, closure 28 can comprise or limit penetrable and resealable part or the element that can seal by apply radiation or energy to it again.In some such embodiments, penetrable and resealable part can be formed by the reclosable thermoplastic of heat, and it can seal pin hole airtightly by apply heat, heating or laser emission or energy to it.In some embodiments, penetrable and resealable part is that laser by apply predetermined wavelength and/or predetermined power to it is reclosable.Penetrable and resealable part limits: (i) predetermined wall thickness on it is axial, (ii) predetermined color and opacity (opacity), it significantly absorbs laser emission of predetermined wavelength and substantially prevents that radiation from passing through its predetermined wall thickness, and/or (iii) predetermined color and opacity, its laser emission that causes predetermined wavelength and/or power pin hole that sealing wherein forms airtightly in predetermined amount of time for example and substantially do not burn described penetrable and resealable part (, aspect the molecular structure of material or chemical property, do not producing irreversible variation).In some embodiments, predetermined amount of time is approximately 2 seconds, is less than or equal to 1.5 seconds or is less than or equal to approximately 1 second.In some embodiments, the predetermined wavelength of laser emission is about 980nm, and the predetermined power of each laser is less than approximately 30 watts or be less than or equal to approximately 10 watts or for approximately 8 to approximately 10 watts.In addition, in these embodiments some, the predetermined color of material is Lycoperdon polymorphum Vitt or green, and predetermined opacity is by limiting with approximately 0.3% Lycoperdon polymorphum Vitt or the green colourant (or pigment) adding in material to approximately 0.6% amount by weight.

In some embodiments, penetrable and resealable part comprises base portion (base portion) or basilar part (underlying portion) and covers sealing again or the resealable part on base portion.In some such embodiments, base portion is in response to can substantially not melting in the time that penetrable and resealable part apply radiation or energy.In some embodiments, thickness penetrable and resealable part and/or resealable part has prevented that enough radiation or energy or its power from arriving base portion substantially.In some embodiments, base portion is formed by the material not sealed again by radiation or energy.In some embodiments, base portion is vulcanite (vulcanized rubber) or silicone (silicone) material.In some embodiments, described material and to be placed for example, for example, at indoor material (, certain drug) compatible (, inertia).In some embodiments, resealable part is thermoplastic.In some embodiments, then hermetic unit is in response to the curable materials of for example radiation or energy, with sealed penetration and at least one of (a) chamber 30 and base portion and (b) form substantially airtight sealing between ambient air.In addition, one or more of basilar part and cover part can have one or more layer.

But, be understood that penetrable and resealable element can for example, by known or become subsequently the function of any (any in multiple different thermoplasticity and/or elastomeric material, comprises for example Low Density Polyethylene) making to implement resealable element described herein in known multiple different materials at present.

In addition, as needs, the lubricant that can add or comprise person of ordinary skill in the relevant's known type in penetrable and resealable part, the formation of granule when penetrating penetrable and resealable part and/or pin or filling element are removed from penetrable and resealable part with pin or filling element preventing or to be otherwise reduced in.In one embodiment, lubricant is mineral oil, its in the time penetrating with pin or other filling element by be enough to prevent or substantially prevent that granuloplastic amount from adding in styrene block copolymer or other thermoplastic compounds.In another embodiment, lubricant is silicone, liquid silicones or the silicone oil for example sold with title " 360Medical Fluid; 350CST " by Dow Corning company, its in the time penetrating with pin or other filling element by be enough to prevent or substantially prevent that granuloplastic amount from adding in styrene block copolymer or other thermoplastic compounds.In such embodiment, the amount of the silicone oil comprising is by weight approximately 0.4% to approximately 1%, for example by weight approximately 0.4% to 0.6%, or even by weight approximately 0.51% to approximately 0.5%.

In addition,, according to some embodiments, closure 28 comprises: the styrene block copolymer of (for example by weight 95%) (i) by weight approximately 80% to approximately 97%; (ii) alkene of approximately 3% to approximately 20% (for example, approximately 5%) by weight, for example ethylene ' alpha '-olefin, polyolefin or alkene; (iii) pigment or coloring agent, its addition is enough to be less than approximately 2 seconds or be less than approximately 1.5 seconds or be less than absorbing laser energy in time period of approximately 1 second for example (but being not limited to), by radiation be transformed into heat depth of fusion equal for example pin hole degree of depth at least about 1/3 to approximately 1/2 stopper material.In some such embodiments, can add be enough to reduce pin and penetrate and/or remove during pin interface frictional force and then substantially prevent the lubricant of granuloplastic amount, for example above-mentioned mineral oil, liquid silicones or silicone oil.

In addition, the needle stroke (stroke) that is configured to can also control the frictional force of pin/material interface generation and/or pass closure 28 that penetrates pin, vacuum equipment, the injection of closure 28 or

load element

32,46,48 is further to reduce or substantially to prevent the formation of granule in the time penetrating stopper with pin.In other embodiments, pin etc. also can at least comprise the lubricant on pin in the interface of the material of pin and closure 28 or reduce the coating of friction.

Except control one or more above-mentioned parameter with reduce and/or eliminate granule formation (for example, in thermoplastic compound, comprise silicone oil or other lubricants, and control the frictional force degree at structure, pin/stopper interface of pin and/or the pin stroke through stopper) outside, or as an alternative, its each can use separately or with being used in combination of any desired, select the different percentage elongations (elongation) of component of penetrable and resealable part to reduce or to eliminate the formation of granule.

According to some such embodiments, penetrable and resealable part can comprise first material with the first percentage elongation, and has the second material of the second percentage elongation that is different from (for example, being less than) described first percentage elongation.In such embodiment, the first material comprises by weight approximately 80% to approximately 97% and limit the first thermoplastic of the first percentage elongation, and the second material comprises by weight approximately 3% to approximately 20% and limit the second thermoplastic of the second percentage elongation that is less than the first material percentage elongation.In some such embodiments, add and be enough to be less than approximately 2 seconds or be less than approximately 1.5 seconds or be less than absorbing laser energy in time period of approximately 1 second for example (but being not limited to), radiation is transformed into heat and seals again for example degree of depth pigment or the coloring agent that equal the amount at least about 1/3 to approximately 1/2 stopper material of the pin hole degree of depth.Penetrable and resealable part optionally comprises lubricant, for example above-mentioned mineral oil, liquid silicones or silicone oil, the formation that its addition is enough to significantly to reduce the frictional force at pin/stopper interface during penetrating stopper with pin and then substantially prevents granule.

In some embodiments, penetrable and resealable part is made up of the material that itself has enough lubricities or otherwise reduce the frictional force between material and pin etc. or comprised lubricant, so just needn't add extra lubricant and/or needn't use above-mentioned pin etc. to reduce or to prevent that granule from forming.For example, the application being incorporated to above and be also that the title of submitting on April 13rd, 2012 is the U.S. Provisional Application No.61/686 of " Modular Filling Apparatus and Method ", the silicone material of describing in 867 has these characteristics, and described document by reference entirety is incorporated to herein.

In some embodiments, the suitable elastomeric material of elastic force that closure 28 returns its original shape by redeformation at least substantially forms, any hole or the breach (breach) at the pin hole position that therefore at least base closed produces after removing pin, therefore prevent that the fluid sterilization agent of injection from escaping from chamber substantially.Then the device 10 that has loaded fluid sterilization agent is transferred to biocide docking station 16 by automaton (not shown) (for example selecting and placement machine).The device 10 that has loaded biocide stops the inner sterilization or the required predetermined parking time of sterilizing that make the device 10 that is exposed to fluid sterilization agent in biocide docking station 16.

In another embodiment, to can be used as be alternatively gaseous sterilization unit 34 to biocide docking station 16.As shown in Figure 2, gaseous sterilization unit 34 comprises the conveyer belt 36 for transporting the device 10 that has loaded biocide.The device 10 that has loaded biocide is placed on conveyer belt 36 and along roundabout and transports by automaton 38, allows to carry out sterilizing with biocide fluid to installing 10 inside in the time that device 10 advances along path.Device 10 paths by gaseous sterilization unit 34 and travelling speed are associated, make inner sterilization or the needed predetermined parking time of sterilizing of the device 10 that is exposed to fluid sterilization agent so that haulage time is at least equaled.

Nitric oxide gas is the little module hydrophobic free base gas of natural generation.The characteristic that NO shows wide reactivity and spreads rapidly by biological entities.For this reason, NO produces in human body natively as a part for health immune defence.Shown that NO is antimicrobial especially in nature, the directly growth of anti-bacteria is also served as murderer in the immunocyte of activation.Verified, in the time of time of NO gas q.s present in an amount sufficient, its inhibition and stop the growth of multiple-microorganism pathogen.Therefore,, along with device 10 betransported by biocide docking station 16 or gaseous sterilization unit 34, in the time that injected NO stops a period of time that is enough to realize sterilizing in chamber, the NO injecting makes the inner surface sterilizing of container.The instruction of person of ordinary skill in the relevant based on herein can recognize, can use equally any in the fluid sterilization agent of multiple other types, comprises known or become subsequently any in the hydroxyl radical gas of known number of different types at present.

In the time that device 10 leaves biocide docking station 16, the inside of device is aseptic, and therefore device is for getting ready in the sterilizing filling of product injection station 18 or filling module.The automaton 40 of for example Fig. 2 of automaton can be transferred to the conveyer belt 42 at product injection station 18 or complete filling station 44 by biocide docking station 16 or gaseous sterilization unit 34 by device 10.At product injection station 18, if wish or need, can for example for example, carry out sterilizing by applying high-intensity ultraviolet (" UV ") radiation or for example, by any other forms of sterilizing known in the art (electron beam irradiation, gamma-radiation or β radiation) the available pin of device being penetrated to surface (surface of closure 28).Then, injecting identical position from biocide or different position pin 46 or vacuum equipment penetrates closure 28 or barrier, and with pin evacuation with for example, from installing 10 sterilization or aseptic inner removing fluids biocide (NO).This finds time also can produce by the vacuum pipeline forming in pin or on the outer perimeter of pin.

Then at the same area of inserting with pin before or different parts, filling pin 46 or filling or injection member are inserted through to closure 28 or barrier, and by pin 46, the product of expectation are loaded in sterilizing room 30 cleanly or with sterile manner.

In some embodiments, may be unnecessary and can not use from the step of installing 10 inner pumping fluid sterilization agent.This can be depending on the product in used fluid sterilization agent and auto levelizer to be loaded.For example, if fluid sterilization agent does not affect product, or be inertia with respect to the product in auto levelizer 10 to be loaded, may there is no need with sterilely removing fluids biocide before filling device 10 of product.In this case, can skip the step of evacuation of fluids biocide, and can in the product filling device 10 with expecting, fluid sterilization agent is still retained in device 10.

In other embodiments, pin 48 can be known and be described in the U.S. Patent No. 6 being above incorporated to, 604, " two-chamber " pin in 561 or multi-cavity pin, described needle set be useful on by product be expelled to first fluid passage in chamber 30 or conduit with for suction during loading or for example by with institute's product filled replacement biocide or by vacuum (for example second fluid passage being connected with vacuum source) make fluid sterilization agent from chamber 30 second fluid passage or conduit out.

In addition, in some embodiments, for example, under the filtrated air of superpressure or other gas (nitrogen or noble gas), carry out the operation of evacuation of fluids biocide and filling device 10, to contribute to keep sterilizing.

After in product is loaded into chamber 30, device 10 is transferred in sealing station 20 to seal the perforation being produced again again.In embodiment shown in Fig. 1, in the time sealing again in station 20, to the pin producing in closure 28 bore a hole apply metered amount fluid sealant 50 (for example silicone sealant) to combine with closure 28 or barrier, and hermetically enclosed thing 28 airtightly.Then device 10 is transferred in curing station 22, pulsed ultraviolet source 52 is to transmitted pulse ultraviolet radiation on fluid sealant 50 so that sealant cures causes it to be transformed into solid phase from liquid phase herein, the pin perforation below of sealing airtightly then.This process has further in the patent application of previously having quoted to be described in detail.

In some embodiments as an alternative, can as mentioned above and carry out laser according to the instruction of following patent and co-pending patent application and seal again produced perforation: the title of authorizing on April 25th, 2006 is " Medicament Vial Having a Heat-sealable Cap, and Apparatus and Method for Filling the Vial " U.S. Patent No. 7, 032, 631, described patent is the U.S. Patent No. 6 of the similar title authorized on October 19th, 2004, 805, 170 part continuation application, the latter is the U.S. Patent No. 6 of authorizing on February 3rd, 2004, 684, 916 continuation application, U.S. Patent No. 6, 684, the 916th, the U.S. Patent No. 6 of the similar title of authorizing on August 12nd, 2003, 604, 561 division, U.S. Patent No. 6, 604, 561 to require again the serial number of similar title of submitting on February 11st, 2000 be No.60/182, the priority of 139 U.S. Provisional Application, and require in the U.S. Provisional Patent Application No.60/442 of the similar title of submission on January 28th, 2003, 526 and the U.S. Provisional Patent Application No.60/484 of similar title that submits on June 30th, 2003, 204 priority, the U.S. Patent No. 7 that the title of authorizing for 5th in JIUYUE in 2006 is " Sealed Containers and Methods of Making and Filling Same ", 100, 646, described patent is the U.S. Patent No. 6 that the title authorized on February 3rd, 2004 is " Medicament Vial Having a Heat-sealable Cap.and Apparatus and Method for Filling the Vial ", 684, 916 part continuation application, the latter is the U.S. Patent No. 6 of the similar title authorized on August 12nd, 2003, 604, 561 division, U.S. Patent No. 6, 604, 561 to require again the serial number of similar title of submitting on February 11st, 2000 be No.60/182, the priority of 139 U.S. Provisional Application, and the title that requires to submit to for 3rd in JIUYUE in 2002 the U.S. Provisional Patent Application No.60/408 that is " Sealed Containers And Methods Of Making And Filling Same ", 068 priority, and be the common unsettled U.S. Provisional Application No.61/476 of " Filling Needle and Method " in the title of submission on April 18th, 2011,523, at this, each of these applications is all incorporated to by reference clearly, using the part as present disclosure, as fully provided in this article.

In other embodiments, the U. S. application No.61/659 being for example above incorporated to for instance, 382 and U.S. Patent No. 7,100, in 646, describe, can be by place covering or the covering part sealed penetration again of assigning on hole, thus substantially airtight sealing at least one of (a) chamber 30 and closure 28 and (b) between ambient air, formed.Described covering or cover part can be used as alternatively or additionally contribute to provide dampness therebetween to see through (moisture vapor transmission, MVT) barrier.In some embodiments, covering or cover part are transparent, so for again sealing after from chamber 30 removing substances, pin or other apparatus for removings can be inserted in chamber 30 through covering, and do not remove covering or closure 28, reduce the exposure of the interior material in chamber 30 to ambient air.

Now, can for example, device 10 be transferred to vanning (boxing) and 58 vanning and the conveyer belt 56 of labelling of standing of labelling by automaton (automaton 54 of Fig. 2), install herein 10 and prepare for subpackage.

In some embodiments, the conveyer belt using can be manufactured " Montrac " conveyer belt by the Montech AG of Switzerland Co., Ltd.For example, for the embodiment of Fig. 2, gaseous sterilization conveyer belt 36, filling conveyer belt 42 and the vanning and the label transport band 56 that move by gaseous sterilization unit 34 can use Montrac conveyer belt separately.Each conveyer belt configures in the known mode of person of ordinary skill in the relevant so that along conveyer belt vehicle 10 separately.

In another embodiment, each module of each disinfection system can comprise multiple stations.For example, the each module of disinfection system can comprise 3 stations.In this exemplary embodiment, each module has 3 ultraviolet disinfection stations (it can comprise ultraviolet disinfection, fluid sterilization agent injection and biocide and stop), 3 find time/vacuum station of NO, 3 product filling stations, 3 fluid sealant stations and 3 ultraviolet curing stations.Can improve or reduce each module station quantity with coupling expect system throughput.

In another embodiment of the present invention, each module of each disinfection system can comprise an only station.In such exemplary, module can comprise a ultraviolet disinfection station, a fluid sterilization agent injection station (it can comprise biocide and stop) and laser and seal station again.In this exemplary embodiment, do not need evacuation of fluids biocide, because it is to product, filling does not have untoward reaction.

In other embodiments, according to the United States Patent (USP) N0.7 that is incorporated to of entirety by reference, 096,896 instruction, can merge one or more above-mentioned station or module and/or its function, thereby exceed a function at a station or position.In some such embodiments, do not need conveyer belt or automaton that device 10 is moved between " combination " stands.

In other embodiments, pin 32,46 and 48 can be combined, thereby make to carry out a kind of function that exceedes in biocide injection, vacuum and filling function with a pin.For example, can utilize pin 32 penetrate closure 28 and inject biocide, then by for example valve or additive method, biocide source and pin be disconnected, and then can pin is connected with vacuum source by for example valve or additive method.In other embodiments, utilize pin 46 penetrate closure 28 and apply vacuum, by for example valve or additive method, vacuum source and pin are disconnected, and make pin be connected to load chamber 30 with product source by for example valve or additive method.In other embodiments, a pin be can only use, biocide, vacuum and product alternately connected.In some such embodiments, can use multi-cavity element (thering is two or more fluid passages), different chambeies connects maybe can connect different sources.In some such embodiments, reduce and need to penetrate closure 28 number of times of (with therefrom removing), reduce total processing time, reduce the number of times penetrating in closure 28, and may decrease and seal again number of times (sealing less hole), improve the sealing integrity of closure, reduced or eliminated the exposed surface of closure 28 needs of sterilizing again, and having reduced the potential pollution to chamber 30 and/or product wherein.

Based on instruction herein, association area those skilled in the art should recognize that the embodiment that can above describe the present invention and other embodiment carry out multiple change and modification, and do not depart from scope of the present invention defined in the appended claims.In addition, can use any above-mentioned feature and combination with one another in any way.Therefore, the invention is not restricted to specifically described embodiment and combination, but can comprise or get rid of the combination of arbitrary characteristics or feature.Therefore, these detailed descriptions of embodiment should be interpreted as to meaning illustrative rather than restrictive.

Claims

1. a method, it comprises the following steps:

(i) utilize injection member to penetrate the penetrable barrier of the empty device of sealing;

(ii) fluid sterilization agent is incorporated in the interior chamber of described device by described injection member;

(iii) allow described fluid sterilization agent in described chamber, to stop the time of q.s so that described chamber is aseptic or sterilization;

(iv) by described barrier by product be incorporated into described aseptic or sterilization chamber in; And

(v) perforation that sealing produces again, to be thickly sealed in described gas product in described chamber.

2. method as defined in claim 1, its be also included in described product be incorporated in described chamber before from described chamber removing fluids biocide.

3. method as defined in claim 2, the wherein said step that removes comprises that the device by inserting through described penetrable barrier carrys out evacuation.

4. method as defined in claim 3, wherein said device limits by described injection member.

5. method as defined in claim 3, the described device wherein inserting through described penetrable barrier is pin.

6. as the method that in claim 1 to 5, any one limited, the step of wherein said introducing product comprises by described injection member introduces described product.

7. as the method that in claim 1 to 5, any one limited, the step of wherein said introducing product comprises and penetrates described penetrable barrier and by described filling element, described product be incorporated in the chamber of described aseptic or sterilization with filling element.

8. as the method that in aforementioned claim, any one limited, wherein said fluid sterilization agent is nitric oxide.

9. as the method that in aforementioned claim, any one limited, it carries out sterilizing or decontamination to the penetrable surface of described barrier before being also included in step (i) and (iv) at least one.

10. method as defined in claim 9, the sterilizing of wherein said penetrable surface or decontamination comprise described penetrable surface are applied to fluid sterilization agent or radiation.

11. methods as defined in claim 10, wherein said fluid sterilization agent is VHP, described radiation is UV.

12. as the method that in aforementioned claim, any one limited, and it is also included in filtrated air or other gas of introducing superpressure during step (i), (ii), (iv) and at least one step (v).

13. as the method that in claim 1 to 12, any one limited, and the wherein said step that seals again comprises to produced perforation and applies fluid sealant.

14. as the method that claim 13 limited, and the wherein said step that seals again also comprises to described fluid sealant and applies radiation or energy, so that described fluid sealant is solidified into solid phase from liquid phase.

15. as the method that claim 14 limited, and wherein said radiation or energy are UV.

16. as the method that in claim 1 to 12, any one limited, and the wherein said step that seals is again included in produced perforation place and applies radiation or energy and described perforation heat is sealed again to described barrier.

17. 1 kinds of equipment, it comprises:

Device, the empty chamber that it comprises sealing and the penetrable barrier being communicated with described chamber; With

The fluid sterilization agent source being communicated with injection member, described injection member is used for penetrating described barrier and by described injection member, fluid sterilization agent being incorporated into the chamber of described device, and allows described fluid sterilization agent in described chamber, to stop the time of q.s so that described chamber is aseptic or sterilization.

18. as the equipment that claim 17 limited, and it also comprises:

Product source, described product is waited to be loaded in described chamber, and fluid is connected communicatively one of in described product source and (a) described injection member and (b) filling element, described filling element is used for utilizing described filling element to penetrate described penetrable barrier, described product is incorporated in the chamber of described aseptic or sterilization by described injection member and described filling element.

19. as the equipment that claim 18 limited, and it also comprises sealing station again, and described sealing again station is for the perforation that sealing produces again, so that described gas product is thickly sealed in described chamber.

20. as claim 18 or 19 devices that limited, and it also comprises fluid sealant source, and described fluid sealant source is for dispense liquid sealant in produced perforation and seal described barrier again.

21. as the device that claim 20 limited, and it also comprises radiation or energy source, and described radiation or energy source for transmitting radiation or energy so that described sealant is solidified into solid phase by liquid phase on described fluid sealant.

22. as the device that claim 19 limited, wherein said sealing again station comprises radiation or energy source, described radiation or energy source are for applying radiation or energy and described perforation heat is sealed again to described barrier in produced perforation place.

23. 1 kinds of equipment, it comprises:

First component, it is for penetrating described penetrable barrier and fluid sterilization agent being incorporated into the chamber of described device by described penetrable barrier, and allows described fluid sterilization agent in described chamber, to stop the time of q.s so that described chamber is aseptic or sterilization.

24. as the equipment that claim 23 limited, and it also comprises second component, described second component for by described penetrable barrier by product be incorporated into described aseptic or sterilization chamber.

25. as the equipment that claim 24 limited, and it also comprises the 3rd parts, and described the 3rd parts are for sealing the perforation producing again.

26. as claim 24 or 25 equipment that limited, it also comprises the 4th parts, described the 4th parts are for utilizing described first component or described second component the penetrable surface of described barrier to be carried out to sterilizing or decontamination before penetrating described barrier.

27. as the equipment that in claim 23 to 26, any one limited, and wherein said first component is injection member and the fluid sterilization agent source being connected communicatively with described injection member fluid; Described second component is the one in injection member and filling element, and the product source being connected communicatively with described injection member or filling element fluid; Described the 3rd parts are fluid sealant or radiation; And described the 4th parts are fluid sterilization agent or radiation.