Method of making and using a flexible, multiple-compartment drug container

• US 6,203,535 B1
• Filed: 11/10/1998
• Issued: 03/20/2001
• Est. Priority Date: 05/13/1996
• Status: Expired due to Term

• Current Assignee: B Braun Medical Incorporated (B. Braun Holding GmbH & Co. KG)
• Original Assignee: B Braun Medical Incorporated (B. Braun Holding GmbH & Co. KG)
• Inventors: Walter, William V., Wu, Nicholas Chung-Hui, Peara, Christopher D., Sandberg, Sharilyn J., McLonis, Mark R., Smith, Steven L., Gharibian, Noel, Sacca, Giuseppe, Pool, Scott L., York, Walter A., Young, H. Theodore, Harvey, Douglas G., Sakaguchi, Thomas R., Barney, Ward W.
• Primary Examiner(s): Weiss, John G.
• Assistant Examiner(s): Cho, David J.
• Application Number:
  US09/189,127
• Time in Patent Office: 861 Days
• Field of Search: 604/408, 604/409, 604/411, 604/412, 604/415, 604/416, 534/10, 534/52, 534/55, 531/332, 534/25
• US Class Current: 604/408
• CPC Class Codes: A61J 1/10 Bag-type containers
• CPC Class Codes: A61J 1/1475 Inlet or outlet ports
• CPC Class Codes: A61J 1/16 Holders for containers
• CPC Class Codes: A61J 1/2024 having peelable seals
• CPC Class Codes: A61J 1/2093 Containers having several compartments for products to be mixed
• CPC Class Codes: A61M 2207/00 Methods of manufacture, assembly or production
• CPC Class Codes: B29C 2793/0027 Cutting off
• CPC Class Codes: B29C 2793/009 after shaping
• CPC Class Codes: B29C 49/0005 characterised by the material
• CPC Class Codes: B29C 49/0691 using sheet like material, e.g. sheet blow-moulding from joined sheets
• CPC Class Codes: B29C 65/00 Joining or sealing of preformed parts , e.g. welding of plastics materials; Apparatus therefor general aspects of processes or apparatus for joining preformed parts B29C66/00; using porous material formed by internal pressure generated therein for joining preformed parts B29C44/1228, B29C44/326
• CPC Class Codes: B29C 65/02 by heating, with or without pressure
• CPC Class Codes: B29C 65/18 using heated tools
• CPC Class Codes: B29C 65/76 Making non-permanent or releasable joints
• CPC Class Codes: B29C 66/112 Single lapped joints
• CPC Class Codes: B29C 66/1122 Single lap to lap joints, i.e. overlap joints B29C66/45, B29C66/472, B29C66/52272 take precedence
• CPC Class Codes: B29C 66/131 Single flanged joints, i.e. one of the parts to be joined being rigid and flanged in the joint area
• CPC Class Codes: B29C 66/133 Fin-type joints, the parts to be joined being flexible the parts to be joined being rigid B29C66/1312
• CPC Class Codes: B29C 66/242 said joint lines being closed, i.e. forming closed contours
• CPC Class Codes: B29C 66/53262 Enclosing spouts between the walls of bags, e.g. of medical bags
• CPC Class Codes: B29C 66/71 : characterised by the composition of the plastics material of the parts to be joined welding bar compositions B29C65/125
• CPC Class Codes: B29C 66/72321 : consisting of metals or their alloys
• CPC Class Codes: B29C 66/7234 : comprising a barrier layer
• CPC Class Codes: B29C 66/72341 : for gases
• CPC Class Codes: B29C 66/72343 : for liquids
• CPC Class Codes: B29C 66/80 : General aspects of machine operations or constructions and parts thereof
• CPC Class Codes: B29C 66/8322 : Joining or pressing tools reciprocating along one axis
• CPC Class Codes: B29K 2009/06 : SB polymers, i.e. butadiene-styrene polymers
• CPC Class Codes: B29K 2023/06 : PE, i.e. polyethylene
• CPC Class Codes: B29K 2023/0641 : MDPE, i.e. medium density polyethylene
• CPC Class Codes: B29K 2023/065 : HDPE, i.e. high density polyethylene
• CPC Class Codes: B29K 2023/08 : Copolymers of ethylene B29K2023/16 takes precedence
• CPC Class Codes: B29K 2023/083 : EVA, i.e. ethylene vinyl acetate copolymer
• CPC Class Codes: B29K 2023/086 : EVOH, i.e. ethylene vinyl alcohol copolymer
• CPC Class Codes: B29K 2023/10 : Polymers of propylene
• CPC Class Codes: B29K 2023/12 : PP, i.e. polypropylene
• CPC Class Codes: B29K 2025/08 : Copolymers of styrene, e.g. AS or SAN, i.e. acrylonitrile styrene B29K2055/02 takes precedence
• CPC Class Codes: B29K 2027/08 : PVDC, i.e. polyvinylidene chloride
• CPC Class Codes: B29K 2027/12 : containing fluorine
• CPC Class Codes: B29K 2067/00 : Use of polyesters or derivatives thereof, as moulding material
• CPC Class Codes: B29K 2067/003 : PET, i.e. poylethylene terephthalate
• CPC Class Codes: B29K 2101/12 : Thermoplastic materials
• CPC Class Codes: B29K 2105/0085 : Copolymers
• CPC Class Codes: B29K 2105/0088 : Blends of polymers
• CPC Class Codes: B29K 2305/02 : Aluminium
• CPC Class Codes: B29K 2705/02 : Aluminium
• CPC Class Codes: B29L 2009/00 : Layered products
• CPC Class Codes: B29L 2009/003 : comprising a metal layer
• CPC Class Codes: B29L 2031/7148 : Blood bags, medical bags
• CPC Class Codes: B31B 2155/00 : Flexible containers made from webs
• CPC Class Codes: B31B 2155/002 : by joining superimposed webs, e.g. with separate bottom webs
• CPC Class Codes: B31B 2170/20 : having multi-layered walls, e.g. laminated or lined
• CPC Class Codes: B31B 2241/00 : Making bags or boxes intended for a specific use
• CPC Class Codes: B31B 70/844 : Applying rigid valves, spouts, or filling tubes
• CPC Class Codes: B32B 15/08 : of synthetic resin
• CPC Class Codes: B32B 27/08 : of synthetic resin
• CPC Class Codes: B32B 27/32 : comprising polyolefins comprising vinyl (co)polymers or acrylic (co)polymers B32B27/30
• CPC Class Codes: B65B 55/16 : by irradiation
• CPC Class Codes: B65D 75/5861 : Spouts B65D75/5811, B65D75/5822 take precedence
• CPC Class Codes: B65D 81/3266 : separated by a common rupturable seal, a clip or other removable fastening device
• CPC Class Codes: C08L 23/0815 : Copolymers of ethene with aliphatic 1-olefins
• CPC Class Codes: C08L 23/142 : at least partially crystalline copolymers of propene with other olefins
• CPC Class Codes: C08L 23/16 : Elastomeric ethene-propene or ethene-propene-diene copolymers, e.g. EPR and EPDM rubbers
• CPC Class Codes: C08L 2666/02 : Organic macromolecular compounds, natural resins, waxes or and bituminous materials
• CPC Class Codes: C08L 2666/04 : Macromolecular compounds according to groups C08L7/00 - C08L49/00, or C08L55/00 - C08L57/00; Derivatives thereof
• CPC Class Codes: C08L 2666/06 : Homopolymers or copolymers of unsaturated hydrocarbons; Derivatives thereof
• CPC Class Codes: C08L 2666/24 : Graft or block copolymers according to groups C08L51/00, C08L53/00 or C08L55/02; Derivatives thereof
• CPC Class Codes: C08L 53/00 : Compositions of block copolymers containing at least one sequence of a polymer obtained by reactions only involving carbon-to-carbon unsaturated bonds; Compositions of derivatives of such polymers
• CPC Class Codes: C08L 53/02 : of vinyl-aromatic monomers and conjugated dienes
• CPC Class Codes: C08L 53/025 : modified
• CPC Class Codes: Y10T 428/13 : Hollow or container type article [e.g., tube, vase, etc.]
• CPC Class Codes: Y10T 428/1341 : Contains vapor or gas barrier, polymer derived from vinyl chloride or vinylidene chloride, or polymer containing a vinyl alcohol unit

Abstract

A flexible container is provided for the storage and mixing together of diluents and medicaments. The container incorporates multiple compartments, separated by peelable seals, in which the diluents and medicaments are stored. The container is constructed of thermoplastic materials having high oxygen and moisture barrier properties which allows the container to be stored for extended periods of time without degrading the contents. The seals are ruptured by manipulation of the container to thereby mix the contents together for delivery through standard IV arrangement to a patient. The seals are constructed to provide a non-linear resistance characteristic to hydraulic pressure, which causes the seal to peel open completely along its length. The container is folded-over along the line of one of the seals and also includes a locking tab and retaining slot to secure the bag in a folded-over condition.

Claims

1. A method for forming a flexible container for combined storage and administration of medicaments and diluents for IV solutions, the method comprising the steps of:

providing a flexible, transparent front sheet;

providing a flexible, vapor impermeable rear sheet, the front and rear sheets sealed together at a common peripheral edge;

heating the front and rear sheets in a first localized area to fuse together the heated portions of the adjoining surfaces, thereby forming a first peelable seal extending between two sides of the common peripheral edge, the first peelable seal separably joining the front and rear sheets to thereby form a first compartment for containing a diluent;

heating the front and rear sheets in a second localized area to fuse together the heated portions of the adjoining surfaces, thereby forming a second peelable seal extending between the two sides of the common peripheral edge, the second peelable seal separably joining the front and rear sheets to thereby form an outlet compartment and a compartment for containing a medicament, the medicament compartment being between the outlet compartment and the diluent compartment;

providing first and second sacrificial ports interposed between the front and rear sheets and in communication with the diluent and medicament compartments, respectively;

filling the diluent compartment with a diluent solution through a respective sacrificial port;

filling the medicament compartment with a medicament through a respective sacrificial port; and

completing the seal along the container'"'"'s common peripheral edge and removing the sacrificial ports from the container, whereby container formation is completed without being subject to a sterilization step after the first compartment filling step.

2. The method according to claim 1 further comprising:

providing an isolator having a sterile environment, the ambient atmosphere within the isolator maintained in a sterile condition, wherein the diluent compartment and medicament compartment are aseptically filled with pre-sterilized diluent and pre-sterilized medicament in the sterile environment inside the isolator.

3. The method according to claim 1, wherein the first and second peelable seals are formed by maintaining the heat seal temperature in the range of from 245°

F. to 265°

F. while applying a pressure in the range of from about 230 psi to about 340 psi for a time in the range of from about 1.5 seconds to about 2.5 seconds.

4. The method according to claim 2 further comprising sterilizing said container before the initial compartment filling step.

5. The method according to claim 4, wherein said sterilization step comprises:

providing a transport carrier;

placing a multiplicity of containers into the transport carrier;

sealing the transport carrier against environmental contamination; and

sterilizing the sealed transport carrier and containers within by application of E-beam radiation.

6. The method of claim 5, wherein said sterilization step further comprises:

placing the E-beam sterilized sealed transport carrier into a UV decontamination chamber;

decontaminating the transport carrier by application of UV radiation; and

introducing the decontaminated transport carrier into the isolator without reexposing the carrier to ambient atmosphere.

7. The method according to claim 4, wherein the finished container is folded-over along the line of the first peelable seal between the medicament and diluent compartment.

8. A method for forming a flexible container for administration of IV solutions, the method comprising the steps of:

providing a flexible front sheet;

providing a flexible rear sheet, the front and rear sheets permanently sealed together around a portion of a common peripheral edge so as to define a volume enclosure therebetween, wherein at least one gap is present in the permanent seal;

providing at least one sacrificial port interposed between the front and rear sheets and in communication with the volume enclosure; and

heating the front and rear sheets in a first localized area to fuse together the heated portions of the adjoining surfaces, thereby forming extension seals in a portion of the container extending between two sides of the common peripheral edge and spaced-away from the at least one sacrificial port, the extension seals and the permanent seal gap defining a channel from said sacrificial port to said volume enclosure.

9. The method according to claim 8 further comprising the steps of:

filling the volume enclosure through said sacrificial port;

completing the permanent seal along the container'"'"'s common peripheral edge so as to interrupt communication between the sacrificial port and the volume enclosure; and

removing the sacrificial port from the container, whereby container formation is completed without being subject to a sterilization step after the volume enclosure is filled.

10. The method according to claim 9 further comprising the step of sterilizing said container before the volume enclosure is filled.

11. The method according to claim 10, wherein said sterilization step is E-beam sterilization.

12. The method according to claim 11, further comprising:

providing an isolator having a sterile environment, the ambient atmosphere within the isolator maintained in a sterile condition, wherein the volume enclosure is aseptically filled with pre-sterilized material.

13. The method according to claim 12, wherein the pre-sterilized material is a pre-sterilized diluent liquid.

14. The method according to claim 12, wherein the pre-sterilized material is a pre-sterilized medicament powder.

15. The method according to claim 10, wherein said sterilization step further comprises:

providing a transport carrier, the transport carrier including a rail cartridge configured to receive and support a multiplicity of containers thereon, the rail cartridge engaging the containers by their respective sacrificial ports;

loading a multiplicity of containers onto the rail cartridge;

placing the loaded rail cartridge into the transport carrier;

sealing the transport carrier against environmental contamination; and

sterilizing the sealed transport carrier and containers within by application of E-beam radiation.

16. The method according to claim 15, wherein said sterilization step further comprises:

introducing the E-beam sterilized sealed transport carrier into a UV decontamination chamber;

decontaminating the transport carrier by application of UV radiation; and

introducing the decontaminated transport carrier into an isolator having a sterile environment, without reexposing the carrier to ambient atmosphere.

17. A method for forming flexible container for combined storage and administration of IV solutions, the method comprising the steps of:

providing a flexible, transparent front sheet;

providing a flexible, vapor impermeable rear sheet;

heating the front and rear sheets in a first localized area to fuse together the heated portions of the adjoining surfaces, thereby forming a permanent seal around a portion of a common peripheral edge of said front and rear sheets, the permanent seal having at least one gap therein providing a channel between said front and rear sheets; and

providing at least one sacrificial port interposed between the front and rear sheets and in communication with the channel for aseptically filling the container.

18. The method according to claim 17 further comprising the step of heating the front and rear sheets in a second localized area to fuse together the heated portions of the adjoining surfaces, thereby forming a peelable seal extending between two sides of the common peripheral edge, the peelable seal separably joining the front and rear sheets to thereby form a first compartment for containing a diluent and a second compartment for containing a medicament.

19. The method according to claim 18, further comprising the step of providing a second sacrificial port interposed between the front and rear sheets, the at least one and second sacrificial ports in communication with the diluent and medicament compartments, respectively.

20. The method according to claim 19 further comprising the steps of:

aseptically filling the diluent compartment with a diluent solution through a respective sacrificial port; and

aseptically filling the medicament compartment with a medicament through a respective sacrificial port.

21. The method according to claim 20 further comprising the step of completing the permanent seal along the container'"'"'s common peripheral edge and removing the sacrificial ports from the container, whereby container formation is completed without being subject to a sterilization step after the compartment filling step.

22. The method according to claim 21, further comprising the step of providing an isolator having a sterile environment, the ambient atmosphere within the isolator maintained in a sterile condition, wherein the diluent compartment and medicament compartment are aseptically filled with pre-sterilized diluent and pre-sterilized medicament in the sterile environment inside the isolator.

23. The method according to claim 21, wherein said peelable seal is formed by maintaining the heat seal temperature in the range of from 245°

F. to 265°

F. while applying a pressure in the range of from about 230 psi to about 340 psi for a time in the range of from about 1.5 seconds to about 2.5 seconds.

24. The method according to claim 22 further comprising the step of sterilizing said container before the first aseptic compartment filling step.

25. A method for forming a flexible container for combined storage and administration of IV solutions, the method comprising the steps of:

providing a flexible, front sheet;

providing a flexible, vapor impermeable rear sheet, the front and rear sheet sealed together at a common peripheral edge;

heating the front and rear sheets in a first localized area to fuse together the heated portions of the adjoining surfaces, thereby forming a permanent seal, the permanent seal being interrupted along its length to define a channel formed between the front and rear sheets;

providing at least one sacrificial port interposed between the front and rear sheets and in communication with the channel for aseptically filling the container;

aseptically filling the container through the at least one sacrificial port; and

completing the seal along the container'"'"'s common peripheral edge and removing the at least one sacrificial port from the container, whereby container formation is completed without being subject to a sterilization step after the first compartment filling step.

26. The method according to claim 25, wherein the front sheet comprises a polypropylene-polyethylene co-polymer blended with styrene ethylene-butylene styrene elastomer.

27. The method according to claim 26, wherein the polypropylene-polyethylene copolymer is blended with styrene ethylene-butylene styrene elastomer in an about 80%/20% wt/wt ratio.

28. The method according to claim 27, wherein the flexible, vapor impermeable rear sheet comprises a multi-layer laminate formed by the steps of:

providing an inner layer of a polypropylene-polyethylene co-polymer blended with a styrene ethylene-butylene styrene elastomer in an about 80%/20% wt/wt ratio interfacing with the front sheet;

providing an intermediate layer of aluminum foil; and

providing an outer thermoplastic layer having a higher melting point than said inner layer.

29. The method according to claim 28, including the steps of:

providing a first peelable seal extending between two opposing sides of the common peripheral edge and separably joining the front and rear sheets to form a compartment containing a diluent;

providing a second peelable seal extending between the two sides of the common peripheral edge and separably joining the front and rear sheets to form thereby an outlet compartment and a compartment containing a medicament which is intermediate the outlet compartment and the diluent compartment;

affixing a clear high-barrier laminate film to the outer surface of the front sheet, the high-barrier laminate film sized to span the front sheet surface between the first and second peelable seals so as to cover the medicament compartment; and

separably sealing an opaque high-barrier protective film over the exterior surface of the clear high-barrier laminate film.

30. The method according to claim 29, wherein the opaque, high-barrier protective film comprises an opaque, peelable, multi-layer laminate including:

an inwardly facing layer formed of a modified ethylene vinyl acetate polymer;

an outwardly facing layer formed of a polyester polymer having a higher melting temperature than said modified ethylene vinyl acetate polymer; and

an aluminum foil layer intermediate the modified ethylene vinyl acetate layer and the polyester polymer layer.

31. The method according to claim 30, wherein the clear high-barrier laminate film comprises:

a polypropylene inner layer disposed adjacent the outer surface of the container front sheet;

a polyester outer layer; and

a clear, transparent high-moisture barrier layer interposed between the inner and outer layers.

32. The method according to claim 31, wherein the clear, high-barrier laminate film further comprises a clear, transparent high-oxygen barrier layer intermediate the polypropylene inner layer and the polyester outer layer.

33. The method according to claim 32, wherein the clear, transparent high-moisture barrier layer is a polymer selected from the group consisting of oriented high-density polyethylene, polychlorotrifluoroethylene, and silica deposited polyethylene terephthalate.

34. The method according to claim 33, wherein the clear, transparent high-oxygen barrier layer is a polymer selected from the group consisting of ethylenevinylalcohol, polyvinylidenechloride coated polyethylene terephthalate, and silica deposited polyvinylalcohol.

35. The method according to claim 30 further comprising the steps of:

folding the container over adjacent the first peelable seal such that the folded-over container'"'"'s outwardly facing surface comprises the multi-layer laminate rear sheet; and

securing the container in a folded-over condition by engaging a locking tab integrally formed with and extending from a side of the container with a slot integrally formed with and extending from the same side of the container as the tab, wherein the tab and slot are moved into position for mutual engagement when the container is folded-over adjacent the first peelable seal to thereby secure the container in a folded over condition.

36. The method according to claim 30, wherein the opaque, high-barrier protective film is separably sealed to the clear high-barrier laminate film by a patterned heat seal head, the pattern forming seal portions alternating with unsealed portions, the sealed portions defining an area smaller than the surface area of the opaque high-barrier film so as to moderate the peel force required to remove the opaque high-barrier film.

37. The method according to claim 29, further including the step of providing a third peelable seal extending between the two sides of the common peripheral edge and separably joining the front and rear sheets to form thereby a sacrificial moisture barrier compartment intermediate the diluent compartment and the medicament compartment.