Containers for parenteral fluids

• US 6,007,529 A
• Filed: 08/04/1997
• Issued: 12/28/1999
• Est. Priority Date: 04/10/1996
• Status: Expired due to Term

• Current Assignee: Fresenius Kabi Oncology PLC (Fresenius SE & Co. KGaA)
• Original Assignee: Pharmacia & Upjohn AB (Pharmacia Corp.)
• Inventors: Lundmark, Stefan, Skolling, Otto, Gustafsson, Bo, Brooling, Cathrine, Berglund, Kjell
• Primary Examiner(s): Stright, Ronald
• Assistant Examiner(s): Cho, David J.
• Application Number:
  US08/905,547
• Time in Patent Office: 876 Days
• Field of Search: 604/408, 604/410, 604/411, 604/415, 604/416, 604/82, 604/85, 604/87, 206/219, 206/221, 383/38, 383/210, 383/211
• US Class Current: 604/410
• CPC Class Codes: A61J 1/00 Containers specially adapted for medical or pharmaceutical purposes capsules or the like for oral use A61J3/07; specially adapted for surgical or diagnostic appliances or instruments A61B50/30; containers for radioactive substances G21F5/00
• CPC Class Codes: A61J 1/10 Bag-type 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: B32B 2307/412 Transparent
• CPC Class Codes: B32B 2307/7244 Oxygen barrier
• CPC Class Codes: B32B 2323/04 Polyethylene
• CPC Class Codes: B32B 2323/10 Polypropylene
• CPC Class Codes: B32B 2367/00 Polyesters, e.g. PET, i.e. polyethylene terephthalate
• CPC Class Codes: B32B 2439/00 Containers; Receptacles closures therefor B32B2435/00
• CPC Class Codes: B32B 27/08 of synthetic resin
• CPC Class Codes: B32B 27/306 comprising vinyl acetate or vinyl alcohol (co)polymers
• CPC Class Codes: B32B 27/32 comprising polyolefins comprising vinyl (co)polymers or acrylic (co)polymers B32B27/30
• CPC Class Codes: B32B 27/36 comprising polyesters
• CPC Class Codes: B32B 7/02 Physical, chemical or physicochemical properties
• CPC Class Codes: B32B 7/12 using interposed adhesives or interposed materials with bonding properties
• CPC Class Codes: B65D 81/268 the absorber being enclosed in a small pack, e.g. bag, included in the package

Abstract

A flexible transparent container for improved storage of oxygen sensitive parenterally administerable agents comprising an inner, primary container enclosed in a substantially oxygen impermeable outer envelope with an oxygen absorber, capable of consuming essentially all residual oxygen after the outer envelope is sealed, and for sufficient period also the oxygen penetrating said envelope. The inner container is made of a polypropylene containing flexible polymeric material compatible with lipophilic agents capable of forming both permanent and peelable seals, while the envelope is made of a substantially water impermeable flexible multilayered polymeric material comprising a first outer substantially water impermeable polymeric film with oxygen barrier forming capacity, assembled with a second, inner polymeric film with a supplementary oxygen barrier forming capacity. The container essentially maintains its characteristics after being subjected to sterilization by steam or radiation.

Claims

1. A flexible transparent container for improved storage of oxygen sensitive parenterally administrable agents comprising an inner, primary container enclosed in a substantially oxygen impermeable outer envelope with an oxygen absorber, capable of consuming essentially all residual oxygen after the outer envelope is sealed as well as the oxygen penetrating said envelope characterized in that:

(i) the inner container is made of a polypropylene containing flexible polymeric material compatible with lipophilic agents capable of forming both permanent and peelable seals, the inner container made of a multilayered film comprising;

a) an outer layer containing a copolyester,

b) an inner sealant layer containing polypropylene, a propylene ethylene copolymer or a mixture of polypropylene or polyethylene and

c) an interior layer containing a thermoplastic elastomer;

(ii) the envelope is made of a substantially water impermeable flexible multilayered polymeric material comprising;

a) a first outer substantially water impermeable polymeric film with oxygen barrier forming capacity, assembled with

b) a second, inner polymeric film with a supplementary oxygen barrier forming capacity;

and in that the container essentially maintains its characteristics after being subjected to sterilization by steam or radiation.

2. A container according to claim 1 characterized in that the inner, primary container is divided into two or more chambers by one or more leak tight peelable seals, possible to rupture by hand from the outside when the contents of the chambers are desired to be mixed and administered to a patient.

3. A container according to claim 2 characterized in that container has at least three chambers comprising an upper chamber, at least one middle chamber and a lower chamber provided with a port system for dispensing a mixed fluid product made from its stored agents and for introducing a supplementary agent.

4. A container according to claim 3 characterized in that said upper chamber is designated to be filled with the agent having the largest volume.

5. A container according to claim 4 characterized in that the inner container has three chambers each designated for a fluid parenteral nutrient of which the lower chamber contains either a lipid emulsion or an amino acid solution.

6. A container according to claim 5 characterized in that the carbohydrate solution comprises glucose and the amino acid solution comprises the essential amino acids.

7. A container according to claim 3 characterized in that the inner container has three parallel chambers of which the upper chamber is filled with a carbohydrate containing aqueous solution, the middle chamber with a lipid emulsion and the lower chamber with an amino acid containing aqueous solution.

8. A container according to claim 3 characterized in that the inner container has three parallel chambers of which the upper container is filled with a carbohydrate containing aqueous solution, the middle chamber with an amino acid containing aqueous solution and the lower chamber with a lipid emulsion.

9. A container according to claim 2 characterized in that the peelable seals seams dividing the chambers of are provided with a rupture zone with reduced strength.

10. A container according to claim 9 characterized in that the rupture zone comprises a point where two straight seams meet in an angle.

11. A container according to claim 10 characterized in that the angle is at least 90°

.

12. A container according to claim 9 characterized in that the rupture zone comprises at least one curved part of the seam.

13. A container according to claim 9 characterized in that the weak seam is straight in the rupture zone.

14. A container according to claim 9 characterized in that it comprises at least two parallel peelable seal seams.

15. A container according to claim 9 characterized in that said rupturable zone is welded with less pressure and/or temperature.

16. A container according to claim 1 characterized in that the inner, primary container is made of a flexible film having a region with higher melt point designated as its outside and a region with lower melt point designated as its sealing inside.

17. A container according to claim 16 characterized in that said inner region with lower melt point is capable of forming both permanent seals and peelable seals when subjected to different welding conditions.

18. A container according to claim 1 characterized in that the outer layer can be subjected to a printing process without subsequent migration of printing ink.

19. A container according to claim 18 characterized in that the outer layer contains a polyester or a copolyester.

20. A container according to claim 1 characterized in that the sealant layer further comprises a thermoplastic elastomer.

21. A container according to claim 1 characterized in that the thermoplastic elastomer is a styrene-ethylene/butadiene-styrene block copolymer.

22. A container according to claim 1 characterized in that the sealing envelope is made of a flexible multilayered transparent material which, after steam sterilizing at 121°

C., provides an oxygen barrier with an oxygen penetration less than 30 cubic centimeters/m², atm, day, when measured at a specific temperature of 25°

C. and 60% relative humidity.

23. A container according to claim 22 characterized in that said envelope forming multilayered material consists of a first outer water impermeable film comprising a metal oxide coated polymeric layer connected to a second inner film comprising an oxygen barrier forming polymeric layer.

24. A container according to claim 23, wherein said outer and inner film is connected by adhesive bonding.

25. A container according to claim 23, wherein the oxygen barrier forming layer of said second inner film comprises (poly)-ethylene vinyl alcohol (EVOH).

26. A container according to claim 23 wherein said second inner film comprises at least one layer containing polypropylene.

27. A container according to claim 23, wherein the first outer film comprises a second layer of polyethylene terephtalate (PET) layer.

28. A container according to claim 27, wherein the first outer film has a first outer layer of polyethylene terephtalate (PET) layer having one side coated with a metal oxide bound to a second layer of polyethylene terephtalate (PET) layer.

29. A container according to claim 28, wherein the first outer polyethylene terephtalate (PET) layer is coated with metal oxide on both sides.

30. A container according to claim 22 characterized in that said outer film comprises a polyethylene terephtalate (PET) layer coated with a metal oxide.

31. A container according to claim 30 characterized in that the metal oxide is selected from silicon oxides, aluminum oxides and titanium oxides.

32. A flexible transparent container for improved storage of oxygen sensitive parenterally administrable agents comprising an inner, primary container enclosed in a substantially oxygen impermeable outer envelope with an oxygen absorber, capable of consuming essentially all residual oxygen after the outer envelope is sealed as well as the oxygen penetrating said envelope characterized in that:

(i) the inner container is made of a polypropylene containing flexible polymeric material compatible with lipophilic agents capable of forming both permanent and peelable seals;

(ii) the envelope is made of a substantially water impermeable flexible multilayered polymeric material comprising;

a) a first outer substantially water impermeable polymeric film with oxygen barrier forming capacity, assembled with

b) a second, inner polymeric film with a supplementary oxygen barrier forming capacity;

and in which the container essentially maintains its characteristics after being subjected to sterilization by steam or radiation, in which the sealing envelope is made of a flexible multilayered transparent material which, after steam sterilizing at 121°

C., provides an oxygen barrier with an oxygen penetration less than 30 cubic centimeters/m², atm, day, when measured at a specific temperature of 25°

C. and 60% relative humidity, wherein said envelope forming multilayered material consists of a first outer water impermeable film comprising a metal oxide coated polymeric layer connected to a second inner film comprising an oxygen barrier forming polymeric layer, wherein said second inner film comprises at least one layer containing polypropylene, and wherein said envelope forming material consists of a film having the structure PET/metal oxide/glue/PET adhesively bound to a film consisting of the structure polypropylene/tielayer/EVOH/tielayer/polypropylene.