CA2296367A1 - Plastic compositions for medical containers and methods for providing such containers and for storing red blood cells - Google Patents
Plastic compositions for medical containers and methods for providing such containers and for storing red blood cells Download PDFInfo
- Publication number
- CA2296367A1 CA2296367A1 CA002296367A CA2296367A CA2296367A1 CA 2296367 A1 CA2296367 A1 CA 2296367A1 CA 002296367 A CA002296367 A CA 002296367A CA 2296367 A CA2296367 A CA 2296367A CA 2296367 A1 CA2296367 A1 CA 2296367A1
- Authority
- CA
- Canada
- Prior art keywords
- container
- copolymer
- approximately
- polyolefin
- plasticizer
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 101
- 229920003023 plastic Polymers 0.000 title claims abstract description 96
- 239000004033 plastic Substances 0.000 title claims abstract description 96
- 238000000034 method Methods 0.000 title claims abstract description 44
- 210000003743 erythrocyte Anatomy 0.000 title abstract description 34
- 229920000098 polyolefin Polymers 0.000 claims abstract description 93
- 239000004014 plasticizer Substances 0.000 claims abstract description 42
- 238000010438 heat treatment Methods 0.000 claims abstract description 31
- 238000003860 storage Methods 0.000 claims abstract description 19
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 claims description 28
- 230000001954 sterilising effect Effects 0.000 claims description 28
- 239000008280 blood Substances 0.000 claims description 27
- 210000004369 blood Anatomy 0.000 claims description 25
- -1 citrate ester Chemical class 0.000 claims description 22
- 210000000601 blood cell Anatomy 0.000 claims description 20
- 229920001400 block copolymer Polymers 0.000 claims description 17
- 238000004659 sterilization and disinfection Methods 0.000 claims description 16
- 206010018910 Haemolysis Diseases 0.000 claims description 15
- 230000008588 hemolysis Effects 0.000 claims description 15
- 229930003427 Vitamin E Natural products 0.000 claims description 14
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 claims description 14
- 235000019165 vitamin E Nutrition 0.000 claims description 14
- 239000011709 vitamin E Substances 0.000 claims description 14
- 229940046009 vitamin E Drugs 0.000 claims description 14
- 239000004952 Polyamide Substances 0.000 claims description 13
- 229920002647 polyamide Polymers 0.000 claims description 13
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 claims description 10
- 239000003381 stabilizer Substances 0.000 claims description 10
- 239000003963 antioxidant agent Substances 0.000 claims description 9
- 235000006708 antioxidants Nutrition 0.000 claims description 9
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 8
- 239000005977 Ethylene Substances 0.000 claims description 8
- 230000003078 antioxidant effect Effects 0.000 claims description 6
- 229920002457 flexible plastic Polymers 0.000 claims description 5
- 239000008188 pellet Substances 0.000 claims description 5
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 5
- 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 claims description 5
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 claims description 4
- DCTZJRUXIXPDJP-UHFFFAOYSA-N trihexyl 2-hydroxy-4-oxoheptane-1,2,3-tricarboxylate Chemical group CCCCCCOC(=O)CC(O)(C(=O)OCCCCCC)C(C(=O)CCC)C(=O)OCCCCCC DCTZJRUXIXPDJP-UHFFFAOYSA-N 0.000 claims description 4
- 229920005606 polypropylene copolymer Polymers 0.000 claims 20
- 239000000843 powder Substances 0.000 claims 2
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 claims 1
- 239000000178 monomer Substances 0.000 claims 1
- 230000005855 radiation Effects 0.000 claims 1
- 239000000463 material Substances 0.000 description 17
- 229920001577 copolymer Polymers 0.000 description 10
- 239000004800 polyvinyl chloride Substances 0.000 description 9
- 230000008569 process Effects 0.000 description 9
- 229920000915 polyvinyl chloride Polymers 0.000 description 8
- KRADHMIOFJQKEZ-UHFFFAOYSA-N Tri-2-ethylhexyl trimellitate Chemical compound CCCCC(CC)COC(=O)C1=CC=C(C(=O)OCC(CC)CCCC)C(C(=O)OCC(CC)CCCC)=C1 KRADHMIOFJQKEZ-UHFFFAOYSA-N 0.000 description 7
- 150000001875 compounds Chemical class 0.000 description 7
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 5
- 150000001860 citric acid derivatives Chemical class 0.000 description 5
- 239000010410 layer Substances 0.000 description 5
- 238000007789 sealing Methods 0.000 description 5
- 239000004804 Butyryltrihexylcitrate Substances 0.000 description 4
- 239000004803 Di-2ethylhexylphthalate Substances 0.000 description 4
- 229920002633 Kraton (polymer) Polymers 0.000 description 4
- 239000004743 Polypropylene Substances 0.000 description 4
- BJQHLKABXJIVAM-UHFFFAOYSA-N bis(2-ethylhexyl) phthalate Chemical compound CCCCC(CC)COC(=O)C1=CC=CC=C1C(=O)OCC(CC)CCCC BJQHLKABXJIVAM-UHFFFAOYSA-N 0.000 description 4
- 239000002985 plastic film Substances 0.000 description 4
- 229920001155 polypropylene Polymers 0.000 description 4
- GWVUTNGDMGTPFE-UHFFFAOYSA-N trihexyl 2-butanoyloxypropane-1,2,3-tricarboxylate Chemical compound CCCCCCOC(=O)CC(C(=O)OCCCCCC)(OC(=O)CCC)CC(=O)OCCCCCC GWVUTNGDMGTPFE-UHFFFAOYSA-N 0.000 description 4
- 238000000862 absorption spectrum Methods 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 210000000265 leukocyte Anatomy 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 230000005012 migration Effects 0.000 description 3
- 238000013508 migration Methods 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 238000006116 polymerization reaction Methods 0.000 description 3
- 230000035899 viability Effects 0.000 description 3
- VXNZUUAINFGPBY-UHFFFAOYSA-N 1-Butene Chemical compound CCC=C VXNZUUAINFGPBY-UHFFFAOYSA-N 0.000 description 2
- KAKZBPTYRLMSJV-UHFFFAOYSA-N Butadiene Chemical compound C=CC=C KAKZBPTYRLMSJV-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 2
- 102000001554 Hemoglobins Human genes 0.000 description 2
- 108010054147 Hemoglobins Proteins 0.000 description 2
- 239000004677 Nylon Substances 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- IAQRGUVFOMOMEM-UHFFFAOYSA-N butene Natural products CC=CC IAQRGUVFOMOMEM-UHFFFAOYSA-N 0.000 description 2
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 229920001778 nylon Polymers 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 239000011148 porous material Substances 0.000 description 2
- 229920005989 resin Polymers 0.000 description 2
- 239000011347 resin Substances 0.000 description 2
- 239000012798 spherical particle Substances 0.000 description 2
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 2
- KWKAKUADMBZCLK-UHFFFAOYSA-N 1-octene Chemical compound CCCCCCC=C KWKAKUADMBZCLK-UHFFFAOYSA-N 0.000 description 1
- 102000015081 Blood Coagulation Factors Human genes 0.000 description 1
- 108010039209 Blood Coagulation Factors Proteins 0.000 description 1
- 235000001018 Hibiscus sabdariffa Nutrition 0.000 description 1
- 101000582864 Homo sapiens Mediator of RNA polymerase II transcription subunit 7 Proteins 0.000 description 1
- 102100030235 Mediator of RNA polymerase II transcription subunit 7 Human genes 0.000 description 1
- 101150034459 Parpbp gene Proteins 0.000 description 1
- 235000005291 Rumex acetosa Nutrition 0.000 description 1
- 240000007001 Rumex acetosella Species 0.000 description 1
- 241000219289 Silene Species 0.000 description 1
- 229930003270 Vitamin B Natural products 0.000 description 1
- 229940087168 alpha tocopherol Drugs 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 235000013405 beer Nutrition 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 239000003114 blood coagulation factor Substances 0.000 description 1
- 238000000071 blow moulding Methods 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- HQQADJVZYDDRJT-UHFFFAOYSA-N ethene;prop-1-ene Chemical group C=C.CC=C HQQADJVZYDDRJT-UHFFFAOYSA-N 0.000 description 1
- 238000001125 extrusion Methods 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- JCYWCSGERIELPG-UHFFFAOYSA-N imes Chemical class CC1=CC(C)=CC(C)=C1N1C=CN(C=2C(=CC(C)=CC=2C)C)[C]1 JCYWCSGERIELPG-UHFFFAOYSA-N 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000005374 membrane filtration Methods 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- XNGIFLGASWRNHJ-UHFFFAOYSA-N phthalic acid Chemical class OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 description 1
- 229920006255 plastic film Polymers 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 238000010057 rubber processing Methods 0.000 description 1
- 239000013049 sediment Substances 0.000 description 1
- 235000003513 sheep sorrel Nutrition 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 229920002397 thermoplastic olefin Polymers 0.000 description 1
- 229960000984 tocofersolan Drugs 0.000 description 1
- 229930003799 tocopherol Natural products 0.000 description 1
- 239000011732 tocopherol Substances 0.000 description 1
- 235000019149 tocopherols Nutrition 0.000 description 1
- TUUQISRYLMFKOG-UHFFFAOYSA-N trihexyl 2-acetyloxypropane-1,2,3-tricarboxylate Chemical compound CCCCCCOC(=O)CC(C(=O)OCCCCCC)(OC(C)=O)CC(=O)OCCCCCC TUUQISRYLMFKOG-UHFFFAOYSA-N 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 235000019156 vitamin B Nutrition 0.000 description 1
- 239000011720 vitamin B Substances 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 238000003466 welding Methods 0.000 description 1
- 239000002076 α-tocopherol Substances 0.000 description 1
- 235000004835 α-tocopherol Nutrition 0.000 description 1
- QUEDXNHFTDJVIY-UHFFFAOYSA-N γ-tocopherol Chemical class OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1 QUEDXNHFTDJVIY-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
- A61J1/00—Containers specially adapted for medical or pharmaceutical purposes
- A61J1/05—Containers specially adapted for medical or pharmaceutical purposes for collecting, storing or administering blood, plasma or medical fluids ; Infusion or perfusion containers
- A61J1/10—Bag-type containers
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08K—Use of inorganic or non-macromolecular organic substances as compounding ingredients
- C08K5/00—Use of organic ingredients
- C08K5/04—Oxygen-containing compounds
- C08K5/10—Esters; Ether-esters
- C08K5/11—Esters; Ether-esters of acyclic polycarboxylic acids
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08K—Use of inorganic or non-macromolecular organic substances as compounding ingredients
- C08K5/00—Use of organic ingredients
- C08K5/04—Oxygen-containing compounds
- C08K5/15—Heterocyclic compounds having oxygen in the ring
- C08K5/151—Heterocyclic compounds having oxygen in the ring having one oxygen atom in the ring
- C08K5/1545—Six-membered rings
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
- C08L23/00—Compositions of homopolymers or copolymers of unsaturated aliphatic hydrocarbons having only one carbon-to-carbon double bond; Compositions of derivatives of such polymers
- C08L23/02—Compositions of homopolymers or copolymers of unsaturated aliphatic hydrocarbons having only one carbon-to-carbon double bond; Compositions of derivatives of such polymers not modified by chemical after-treatment
- C08L23/10—Homopolymers or copolymers of propene
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
- C08L2205/00—Polymer mixtures characterised by other features
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
- C08L53/00—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
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
- C08L77/00—Compositions of polyamides obtained by reactions forming a carboxylic amide link in the main chain; Compositions of derivatives of such polymers
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T428/00—Stock material or miscellaneous articles
- Y10T428/13—Hollow or container type article [e.g., tube, vase, etc.]
- Y10T428/1352—Polymer or resin containing [i.e., natural or synthetic]
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T428/00—Stock material or miscellaneous articles
- Y10T428/13—Hollow or container type article [e.g., tube, vase, etc.]
- Y10T428/1352—Polymer or resin containing [i.e., natural or synthetic]
- Y10T428/1386—Natural or synthetic rubber or rubber-like compound containing
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T428/00—Stock material or miscellaneous articles
- Y10T428/13—Hollow or container type article [e.g., tube, vase, etc.]
- Y10T428/1352—Polymer or resin containing [i.e., natural or synthetic]
- Y10T428/139—Open-ended, self-supporting conduit, cylinder, or tube-type article
- Y10T428/1393—Multilayer [continuous layer]
Abstract
Plastic compositions, containers (10) useful in the storage of red blood cells, and methods for providing such red blood cell storage containers (10) and for storing red blood cells are disclosed. The plastic composition includes a polyolefin copolymer and a plasticizer. The flexibility of such plastic compositions and containers (10) made thereof is substantially unchanged upon heating to a high temperature relative to its flexibility before such heating.
Description
PLASTIC COMPOSITIONS FOR MED7:CAL CONTAINERS
AND METI~ODS FOR PROVIDING SL1CH CONTAINERS
AND FOR STORING RED BLOOD CELLS
The present invention relates, in general, to plastic compositions and, in pari~icular, to plastic compositions that may be used for medical containers, such as containers for the storage of blood and/or blood cells. More particularly, the present invention relates to plastic compositions, to plastic containers made from such compositions and to methods for containing or storing whole blood or blood cells, such as red blood cells, which suppresses the hemolysis of blood cells.
BACKGROUND
Whole blood is typically described as being made up of various cellular components such as red blood cells (RBCs), white blood cells (WBCs) and platelets, suspended in a liquid component, plasma. Each component plays a specific and important role in the human body. For example, platelets (together with clotting factors and other substances in the blood) are responsible for stopping b7Leeding. WBCs are primarily responsible for fighting disease. RBCs transport oxygen (O~) and carbon dioxide (COZ) to and from body tissues . The OZ and CCi? are carried by a protein called hemoglobin, which is found inside the RBC.
Whole blood can be (and is routinely) separated by centrifugation, membrane filtration or other techniques into its constituent components, and the separated component may be administered to a patient in need of that particular component. For example, RBCs may be administered to patients who have experienced rapid blood loss or to improve the oxygen carrying capability of blood in patients suffering from anemia and the like.
Most commonly, RBCs are separated from whole blood by introducing anticoagulated whole blood into a rotating centrifuge chamber. More specifically, whole blood is withdrawn from a donor through a needle that is inserted into the vein of the donor. The needle communicates with plastic tubing through which the blood flows to a (usually preattached) plastic container. The blood inside the plastic container is then subjected to a centrifugal force by rotating the centrifuge. Rotation of the centrifuge causes the components of whole blood to sediment into layers or bands based on the different densities of the components. The more dense (or "heavier") components, such as RBCs, are thus "separated" from the lighter components, such as platelets and plasma. The separated layer or band of RBCs may then be transferred to a separate (usuall;y plastic) cantainer where they are stored until transfusion to a patient.
Alternatively, the plasma and platelets may be expressed from the collection container, leaving the RBCs in the collection container for storage.
For a variety of reasons, the storage period can last several days and sometimes even several weeks.
Unfortunately, extended storage of RBCs may negatively affect the function and viability of RBCs.
For example, one concern during the storage of RBCs is that the membrane surrounding the RBC cell will rupture. The rupturing of the RBC membrane is commonly referred to as "hemolysis~". The hemolysis of RBCs results in the release of hemoglobin, thus, impairing the RBC~s ability to transport Oz and C
These RBCs are less suitable for transfusion to a patient.
WO 99/039?A fCT/US98/12949 The plastic containers used for the storage of blood and/or blood cells must be made of materials that are, of course, suitable for the storage of blood and, preferably, enhance the viability of the stored blood cells. Some plastics, that may be otherwise suitable for storing blood and/or blood cells, may be too rigid for use in medical containers. Accordingly, these materials require a plasticizes to soften the material and provide the container with flexibility.
One such material that has beer, commonly used for medical containers is polyvinyl chloride (PVC).
Because PVC alone is too rigid to be used for flexible blood containers, it is typically combined with a plasticizes.
Several different plasticize~rs are suitable for use with PVC. For example, plasticizers from the family of phthalate esters, and in particular, di-2-ethylhexylphthalate (DEHP) have been used in combination with PVC resins. In addition to DEHP, plasticizers such as triethylhexyltrimellitate (TEHTM) have also been used with PVC resins. More .recently, it has been discovered that citrate esters are capable of plasticizing PVC. PVC plasticized witrn citrate ester is described, for example, in U.S. Patent Nos.
AND METI~ODS FOR PROVIDING SL1CH CONTAINERS
AND FOR STORING RED BLOOD CELLS
The present invention relates, in general, to plastic compositions and, in pari~icular, to plastic compositions that may be used for medical containers, such as containers for the storage of blood and/or blood cells. More particularly, the present invention relates to plastic compositions, to plastic containers made from such compositions and to methods for containing or storing whole blood or blood cells, such as red blood cells, which suppresses the hemolysis of blood cells.
BACKGROUND
Whole blood is typically described as being made up of various cellular components such as red blood cells (RBCs), white blood cells (WBCs) and platelets, suspended in a liquid component, plasma. Each component plays a specific and important role in the human body. For example, platelets (together with clotting factors and other substances in the blood) are responsible for stopping b7Leeding. WBCs are primarily responsible for fighting disease. RBCs transport oxygen (O~) and carbon dioxide (COZ) to and from body tissues . The OZ and CCi? are carried by a protein called hemoglobin, which is found inside the RBC.
Whole blood can be (and is routinely) separated by centrifugation, membrane filtration or other techniques into its constituent components, and the separated component may be administered to a patient in need of that particular component. For example, RBCs may be administered to patients who have experienced rapid blood loss or to improve the oxygen carrying capability of blood in patients suffering from anemia and the like.
Most commonly, RBCs are separated from whole blood by introducing anticoagulated whole blood into a rotating centrifuge chamber. More specifically, whole blood is withdrawn from a donor through a needle that is inserted into the vein of the donor. The needle communicates with plastic tubing through which the blood flows to a (usually preattached) plastic container. The blood inside the plastic container is then subjected to a centrifugal force by rotating the centrifuge. Rotation of the centrifuge causes the components of whole blood to sediment into layers or bands based on the different densities of the components. The more dense (or "heavier") components, such as RBCs, are thus "separated" from the lighter components, such as platelets and plasma. The separated layer or band of RBCs may then be transferred to a separate (usuall;y plastic) cantainer where they are stored until transfusion to a patient.
Alternatively, the plasma and platelets may be expressed from the collection container, leaving the RBCs in the collection container for storage.
For a variety of reasons, the storage period can last several days and sometimes even several weeks.
Unfortunately, extended storage of RBCs may negatively affect the function and viability of RBCs.
For example, one concern during the storage of RBCs is that the membrane surrounding the RBC cell will rupture. The rupturing of the RBC membrane is commonly referred to as "hemolysis~". The hemolysis of RBCs results in the release of hemoglobin, thus, impairing the RBC~s ability to transport Oz and C
These RBCs are less suitable for transfusion to a patient.
WO 99/039?A fCT/US98/12949 The plastic containers used for the storage of blood and/or blood cells must be made of materials that are, of course, suitable for the storage of blood and, preferably, enhance the viability of the stored blood cells. Some plastics, that may be otherwise suitable for storing blood and/or blood cells, may be too rigid for use in medical containers. Accordingly, these materials require a plasticizes to soften the material and provide the container with flexibility.
One such material that has beer, commonly used for medical containers is polyvinyl chloride (PVC).
Because PVC alone is too rigid to be used for flexible blood containers, it is typically combined with a plasticizes.
Several different plasticize~rs are suitable for use with PVC. For example, plasticizers from the family of phthalate esters, and in particular, di-2-ethylhexylphthalate (DEHP) have been used in combination with PVC resins. In addition to DEHP, plasticizers such as triethylhexyltrimellitate (TEHTM) have also been used with PVC resins. More .recently, it has been discovered that citrate esters are capable of plasticizing PVC. PVC plasticized witrn citrate ester is described, for example, in U.S. Patent Nos.
4,710,532, 4,789,700, 4,870,204, 4,883,905, 4,892,967, 4,931,583, 4,824,893, 4,711,922 and 4,954,64'9, all of which are incorporated by reference herein.
It has been observed that some plasticizers appear to have a beneficial effect on the viability of stored blood and/or red blood cells. More ' specifically, it has been observed that red blood cells stored in plastic containers that include ' certain plasticizers experience a lower rate of hemolysis than in containers free of plasticizers. It is believed that the interaction of the stored blood cells and the plasticizes (in t:he container wall) helps maintain the integrity of the RBC membrane, thus WO 99/03924 PCT/US98/t2949 resulting in reduced hemolysis. 'thus, even for those materials that are not as rigid as PVC and are otherwise suitable for use in the storage of blood, it may be beneficial that the plastic container include a sufficient amount of plasticize:r to reduce the rate of hemolysis in the stored blood.
Examples of such blood storage containers are described in U.S. Patent Nos . 5, 026, 347, 5, 100, 401 and 5,167,657, all of which are assigned to the assignee of the present of application and are incorporated by reference herein. The blood storage containers described therein are made from a plastic composition that includes polyolefin and citrate ester plastisizers. The polyolefin described in these patents, is a polyolefin copolymer that includes a central block of ethylene and t>utylene units with terminal blocks of styrene. The polyolefin is combined with a citrate ester pl~asticizer to form a plastic composition that is suit:able for use in a blood storage container and wherein the amount of citrate ester is sufficient to suppress the level of hemolysis in stored red blood cells. The plastic material described therein may further in~:.lude an amount of propylene.
Although the above described containers are believed to have worked satisfactorily, it has been observed that some polyolefins, when combined with plasticizers, appear to lose some of their flexibility and become more brittle after beir,~g subjected to high temperature heating (such as occurs during steam sterilization). It is believed that at least: part of the reason for the material becoming more brittle after sterilization may be that. high temperature heating results in a molecular rearrangement of the material, which increases the crystallinity (and, therefore, rigidity) of the material. However, in addition, it is believed that the decrease in WO 99/03924 fCT/US98/12949 flexibility results from the inability of the plastic . material to retain the plasticize~r within the body of the plastic material. Stated differently, it is believed that during heating, the plasticizes migrates 5 out from the plastic material to the outer surface of the material. The migration of the plasticizes, therefore, results in there being less plasticizes available for contact with the stored blood cells.
Ultimately, this may lead to reduced hemolysis suppression in the stored red blood cells. Far these reasons, it is desirable to provide a plastic composition that can be used as .a medical container, such as a container for storing blood and/or red blood cells, which remains flexible afi;.er being exposed to heat and/or retains most of the plasticize~r during heating, such as in a steam sterilization process.
SUMMARY OF THE CLAIMED INVENTIONS
There are several different aspects to the present invention which may be employed together or separately without departing from the present invention.
For example, in one aspect, the present invention is directed to a flexible plastic composition that includes a polyolefin copolymer and a plasi=icizer.
The flexibility of the plastic composition remains substantially unchanged upon heating to a sterilizing temperature relative to its flexibility before heating.
In another aspect, the present invention is also ' directed to flexible plastic containers defined by a container wall where at least a portion of the ' container wall interior is made of a plastic composition that includes a polyolefin copolymer and a plasticizes. The flexibility of the plastic container remains substantially unchanged upon heating to a sterilizing temperature relative to its WO 99/03924 ~CT/US98/12949 flexibility before such heating.
In another aspect, the present invention is also directed to methods for providing a blood storage container. The method includes providing a first polyolefin copolymer and combining the F~olyolefin copolymer with a plasticizer to form a. plastic composition. The plastic composition is extruded, formed into sheets which are 'then formed into a container. The container is then sterilized. The flexibility of the container rE:mains substantially unchanged after heating to a sterilizing temperature relative to its flexibility before such heating.
The present invention is also directed to a method for storing red blood cells. The method includes providing a flexible plastic container having at least a portion of its interior surface made of a plastic composition that includes a polyolefin copolymer and a material capable of suppressing the hemolysis of red blood cells, such as a plasticizer.
The flexibility of the plastic container remains substantially unchanged after heating to a sterilizing temperature relative to its flexibility before such heating. The method includes introducing a quantity of blood cells into the container and maintaining the quantity of blood cells within the container.
BRIEF DESCRIPTION OF THE DRAWINGS
Fig. 1 is a plan view of a medical container, with a portion broken away, depicting one embodiment of the present invention;
Fig. 2 is a side view of a medical container with a portion broken away, depict:Lng an alternative embodiment of the present invention;
Fig. 3 is the Fourier Transform Infrared (FTIR) absorbance spectra for certain medical containers embodying the present invention prior i:o steam sterilization;
WO 99/03924 1PC'T/US98/12949 Fig . 4 is the FTIR absorbance spectra f or certain medical containers embodying the present invention after 20 minutes of steam steril_'Lzation;
Fig. 5 is the FTIR absorbance spectra for certain medical containers embodying the present invention after 60 minutes of steam sterilization.
DETAILED DESCRIPTION OF THE DISCLOSED EMBODIMENTS
The following detailed description is not intended to set forth all possible variations or applications of the present invention. For this reason, the scope of the invention is not defined by or limited to the embodiments described below, but by the appended claims. Accordingly, the present invention includes future variations or embodiments not presently appreciated by the inventor, but that would be apparent to persons of ordinary skill upon reading this description.
Turning now to the figures, Fig. 1 shows a plastic container 10 made in accordance with the present invention. Container 10 includes facing flat walls 12 and 14 made of flexible, plastic sheets sealed together at their periphery 16 in a manner known to those skilled in the art, such as heat sealing, radio frequency heat sealing and sonic welding. Other techniques for providing a container, which does not require sealing of sheets, such as blow molding may also be used. Of course, the present invention is not limited to how the container is formed. Container 10 may also include at :least one ' blood collection tube 18.
In one embodiment of the present invention, walls ' 12 and 14 may be made entirely of the plastic composition of the present invention. Alternatively, only the interior surface 19 (the side of the wall that would be in contact with the blood during storage) or even a portion of the interior surface 19 of walls 12 and 14 may be made of the plastic composition of the present invention. Referring to Figs. 1 and 2, container walls 12 and 14 may be made of a single layer of the pla~;tic composition or, alternatively, as shown in Fig. :?, container walls 12 and 14 may be made of two or more layers 20 and 22 laminated or coextruded together wherein at least the inner layer 20 or a portion of inner layer 20 is made of the plastic composition of the present invention.
The plastic composition may be any flexible polyolefin or copolymer thereof that is suitable for use in the extended storage of :red blood cells and, preferably, is steam steril_izable. Certain polyolefins combined with plasticizes are suitable for use in the storage of red blood cells with suppressed hemolysis. However, as discussed above, it. has been observed that some of the polyolefin-based compositions appear to lose some of their flexibility upon high temperature heating (such as occurs during steam sterilization). It is believed that one reason for the decreased flexibility may be the migration of plasticizes from the composition becausE: of the polyolefin's inability to retain the plasticizes.
Thus, in one aspect of the present invention, the plastic composition includes at. least one non-PVC
plastic, such as polyolefin or a copolymer thereof, where the flexibility of the plastic composition remains substantially unchanged after heating to a sterilizing temperature relative to the flexibility of the composition before heating. More specifically, the polyolefins and polyolefin copolymers of such composition should be suitable for mixing and compounding with plasticizes, and capable of adsorbing plasticizes and retaining the plas;ticizer during steam sterilization or other high temperature heating.
Although many different polyolefins and copolymers thereof are compatible with plasticizers and are able to adsorb the plasticizer, certain polyolefins prepared by certain polymerization processes (and utilizing certain catalysts for such polymerization) may be better suited for use in plastic compositions of the present invention. For example, polyolefins prepared by the so called "Catalioy" process provide polyolefin copolymers that are capable of adsorbing and regaining most of the original plasticizer even after ..team steri:Lization.
The "Catalloy" process is described generally in U.S.
Patent No. 5,302,454 which is incorporated by reference herein. As set forth in U.S. Patent No.
5,302,454, the Catalloy polymerization process includes at least two stages. :Cn the first stage, polypropylene is polymerized to form a polypropylene backbone (which can be a homopolym~er of polypropylene ) and, in the following stages ethylene-propylene and possibly other polymers such as butadiene, butene, and octene are polymerized and added to the polypropylene.
The Catalloy process results in spherical particles having a certain porosity and density which, it is believed, makes them effective in adsorbing plasticizers and retaining the plasticize:r during steam sterilization at about 120C:. Specifically, it is believed that the plasticizer, when combined with the spherical particles of the polyolefin copolymer, quickly and easily migrates into the pores of the particles. The plasticizer remains embedded within the pores of the polyolefin spheres and is less susceptible to migration to the surface of the container wall during, for examplE~, exposure to heat.
Nonetheless, it is understood and believed that the plasticizer is still capable of reducing or suppressing the hemolysis of RBC with the container.
Examples of such polyolefin copolymers are the thermoplastic olefins (which are polyolefin capolymers of polypropylene, ethylene and butene) KS-050, KS-052P, KS-059P, KS-051P, all available from Montell Technology Company HV, Hoofddorp, The Netherlands. In addition to the polyolefins obtained by the Catalloy process, the "Spheripol~~ and "Spherilene~~ processes 5 also provide polyolefin copolymers having characteristics similar to the "Catalloy~~ polyolefin copolymers. Examples of such polyolefin copolymers are copolymers of polypropylene ~;uch as SA-E349S, also available from Montell Technology Company BV.
It has been observed that some plasticizers appear to have a beneficial effect on the viability of stored blood and/or red blood cells. More ' specifically, it has been observed that red blood cells stored in plastic containers that include ' certain plasticizers experience a lower rate of hemolysis than in containers free of plasticizers. It is believed that the interaction of the stored blood cells and the plasticizes (in t:he container wall) helps maintain the integrity of the RBC membrane, thus WO 99/03924 PCT/US98/t2949 resulting in reduced hemolysis. 'thus, even for those materials that are not as rigid as PVC and are otherwise suitable for use in the storage of blood, it may be beneficial that the plastic container include a sufficient amount of plasticize:r to reduce the rate of hemolysis in the stored blood.
Examples of such blood storage containers are described in U.S. Patent Nos . 5, 026, 347, 5, 100, 401 and 5,167,657, all of which are assigned to the assignee of the present of application and are incorporated by reference herein. The blood storage containers described therein are made from a plastic composition that includes polyolefin and citrate ester plastisizers. The polyolefin described in these patents, is a polyolefin copolymer that includes a central block of ethylene and t>utylene units with terminal blocks of styrene. The polyolefin is combined with a citrate ester pl~asticizer to form a plastic composition that is suit:able for use in a blood storage container and wherein the amount of citrate ester is sufficient to suppress the level of hemolysis in stored red blood cells. The plastic material described therein may further in~:.lude an amount of propylene.
Although the above described containers are believed to have worked satisfactorily, it has been observed that some polyolefins, when combined with plasticizers, appear to lose some of their flexibility and become more brittle after beir,~g subjected to high temperature heating (such as occurs during steam sterilization). It is believed that at least: part of the reason for the material becoming more brittle after sterilization may be that. high temperature heating results in a molecular rearrangement of the material, which increases the crystallinity (and, therefore, rigidity) of the material. However, in addition, it is believed that the decrease in WO 99/03924 fCT/US98/12949 flexibility results from the inability of the plastic . material to retain the plasticize~r within the body of the plastic material. Stated differently, it is believed that during heating, the plasticizes migrates 5 out from the plastic material to the outer surface of the material. The migration of the plasticizes, therefore, results in there being less plasticizes available for contact with the stored blood cells.
Ultimately, this may lead to reduced hemolysis suppression in the stored red blood cells. Far these reasons, it is desirable to provide a plastic composition that can be used as .a medical container, such as a container for storing blood and/or red blood cells, which remains flexible afi;.er being exposed to heat and/or retains most of the plasticize~r during heating, such as in a steam sterilization process.
SUMMARY OF THE CLAIMED INVENTIONS
There are several different aspects to the present invention which may be employed together or separately without departing from the present invention.
For example, in one aspect, the present invention is directed to a flexible plastic composition that includes a polyolefin copolymer and a plasi=icizer.
The flexibility of the plastic composition remains substantially unchanged upon heating to a sterilizing temperature relative to its flexibility before heating.
In another aspect, the present invention is also ' directed to flexible plastic containers defined by a container wall where at least a portion of the ' container wall interior is made of a plastic composition that includes a polyolefin copolymer and a plasticizes. The flexibility of the plastic container remains substantially unchanged upon heating to a sterilizing temperature relative to its WO 99/03924 ~CT/US98/12949 flexibility before such heating.
In another aspect, the present invention is also directed to methods for providing a blood storage container. The method includes providing a first polyolefin copolymer and combining the F~olyolefin copolymer with a plasticizer to form a. plastic composition. The plastic composition is extruded, formed into sheets which are 'then formed into a container. The container is then sterilized. The flexibility of the container rE:mains substantially unchanged after heating to a sterilizing temperature relative to its flexibility before such heating.
The present invention is also directed to a method for storing red blood cells. The method includes providing a flexible plastic container having at least a portion of its interior surface made of a plastic composition that includes a polyolefin copolymer and a material capable of suppressing the hemolysis of red blood cells, such as a plasticizer.
The flexibility of the plastic container remains substantially unchanged after heating to a sterilizing temperature relative to its flexibility before such heating. The method includes introducing a quantity of blood cells into the container and maintaining the quantity of blood cells within the container.
BRIEF DESCRIPTION OF THE DRAWINGS
Fig. 1 is a plan view of a medical container, with a portion broken away, depicting one embodiment of the present invention;
Fig. 2 is a side view of a medical container with a portion broken away, depict:Lng an alternative embodiment of the present invention;
Fig. 3 is the Fourier Transform Infrared (FTIR) absorbance spectra for certain medical containers embodying the present invention prior i:o steam sterilization;
WO 99/03924 1PC'T/US98/12949 Fig . 4 is the FTIR absorbance spectra f or certain medical containers embodying the present invention after 20 minutes of steam steril_'Lzation;
Fig. 5 is the FTIR absorbance spectra for certain medical containers embodying the present invention after 60 minutes of steam sterilization.
DETAILED DESCRIPTION OF THE DISCLOSED EMBODIMENTS
The following detailed description is not intended to set forth all possible variations or applications of the present invention. For this reason, the scope of the invention is not defined by or limited to the embodiments described below, but by the appended claims. Accordingly, the present invention includes future variations or embodiments not presently appreciated by the inventor, but that would be apparent to persons of ordinary skill upon reading this description.
Turning now to the figures, Fig. 1 shows a plastic container 10 made in accordance with the present invention. Container 10 includes facing flat walls 12 and 14 made of flexible, plastic sheets sealed together at their periphery 16 in a manner known to those skilled in the art, such as heat sealing, radio frequency heat sealing and sonic welding. Other techniques for providing a container, which does not require sealing of sheets, such as blow molding may also be used. Of course, the present invention is not limited to how the container is formed. Container 10 may also include at :least one ' blood collection tube 18.
In one embodiment of the present invention, walls ' 12 and 14 may be made entirely of the plastic composition of the present invention. Alternatively, only the interior surface 19 (the side of the wall that would be in contact with the blood during storage) or even a portion of the interior surface 19 of walls 12 and 14 may be made of the plastic composition of the present invention. Referring to Figs. 1 and 2, container walls 12 and 14 may be made of a single layer of the pla~;tic composition or, alternatively, as shown in Fig. :?, container walls 12 and 14 may be made of two or more layers 20 and 22 laminated or coextruded together wherein at least the inner layer 20 or a portion of inner layer 20 is made of the plastic composition of the present invention.
The plastic composition may be any flexible polyolefin or copolymer thereof that is suitable for use in the extended storage of :red blood cells and, preferably, is steam steril_izable. Certain polyolefins combined with plasticizes are suitable for use in the storage of red blood cells with suppressed hemolysis. However, as discussed above, it. has been observed that some of the polyolefin-based compositions appear to lose some of their flexibility upon high temperature heating (such as occurs during steam sterilization). It is believed that one reason for the decreased flexibility may be the migration of plasticizes from the composition becausE: of the polyolefin's inability to retain the plasticizes.
Thus, in one aspect of the present invention, the plastic composition includes at. least one non-PVC
plastic, such as polyolefin or a copolymer thereof, where the flexibility of the plastic composition remains substantially unchanged after heating to a sterilizing temperature relative to the flexibility of the composition before heating. More specifically, the polyolefins and polyolefin copolymers of such composition should be suitable for mixing and compounding with plasticizes, and capable of adsorbing plasticizes and retaining the plas;ticizer during steam sterilization or other high temperature heating.
Although many different polyolefins and copolymers thereof are compatible with plasticizers and are able to adsorb the plasticizer, certain polyolefins prepared by certain polymerization processes (and utilizing certain catalysts for such polymerization) may be better suited for use in plastic compositions of the present invention. For example, polyolefins prepared by the so called "Catalioy" process provide polyolefin copolymers that are capable of adsorbing and regaining most of the original plasticizer even after ..team steri:Lization.
The "Catalloy" process is described generally in U.S.
Patent No. 5,302,454 which is incorporated by reference herein. As set forth in U.S. Patent No.
5,302,454, the Catalloy polymerization process includes at least two stages. :Cn the first stage, polypropylene is polymerized to form a polypropylene backbone (which can be a homopolym~er of polypropylene ) and, in the following stages ethylene-propylene and possibly other polymers such as butadiene, butene, and octene are polymerized and added to the polypropylene.
The Catalloy process results in spherical particles having a certain porosity and density which, it is believed, makes them effective in adsorbing plasticizers and retaining the plasticize:r during steam sterilization at about 120C:. Specifically, it is believed that the plasticizer, when combined with the spherical particles of the polyolefin copolymer, quickly and easily migrates into the pores of the particles. The plasticizer remains embedded within the pores of the polyolefin spheres and is less susceptible to migration to the surface of the container wall during, for examplE~, exposure to heat.
Nonetheless, it is understood and believed that the plasticizer is still capable of reducing or suppressing the hemolysis of RBC with the container.
Examples of such polyolefin copolymers are the thermoplastic olefins (which are polyolefin capolymers of polypropylene, ethylene and butene) KS-050, KS-052P, KS-059P, KS-051P, all available from Montell Technology Company HV, Hoofddorp, The Netherlands. In addition to the polyolefins obtained by the Catalloy process, the "Spheripol~~ and "Spherilene~~ processes 5 also provide polyolefin copolymers having characteristics similar to the "Catalloy~~ polyolefin copolymers. Examples of such polyolefin copolymers are copolymers of polypropylene ~;uch as SA-E349S, also available from Montell Technology Company BV.
10 Of course the polyolefin copolymer is not limited to polyolefin copolymers prepared by the above-described processes and any other polyolefin or polyolefin copolymer capable of adsorbing and retaining plasticizes after sterilization may be used.
Alternatively, two or more of the above polyolefins and/or copolymers thereof may be combined. For example, in one embodiment, both KS-051P and SA-8495 polyolefin copolymers may be used in the' plastic composition. It should be understood that the above described Catalloy and Spheripol polymers are available in a non-porous pellet and porous spherical forms. In the plastic composition of the present invention, it is preferred that at least one of the copolymers is of the porous spherical variety so as to better adsorb the plasticizes.
The polyolefin or polyolefin copolymers described above may be combined with a selected amaunt of a suitable plasticizes and/or other material that is capable of suppressing the hemolysis of r_ed blood cells. A plasticizes compatible with the polyolefin copolymer (that is, capable of being mixed and compounded with the polyolefin copolymer and being retained by the polyolefin copolymer during heating ) is preferred. Plasticizers capable of being' combined with the polyolefin copolymers described above include, but are not limited to, DEHP, TEHTM and, preferably, citrate esters. Of course, other known materials capable of suppressing hemolysis may also be used. Preferably citrate esters of the formula CHI COOR, R, COOC-COORz where : R" R2 and R3 = CHj to C,BH3, and R, = CH3 to C,Hls may be combined with the po.lyolefin copolymers described above. For example, citrate esters such as acetyltri-n-hexyl citrate, n-butyryltri-n-hexyl citrate, acetyltri-n-(hexyl/octyl/decyl/citrate or acetyltri-n-(octyl/decyl) citrate are suitable and n-butyryltri-n-hexyl citrate (sorrel=imes abbreviated as BTHC) is preferred. Such citrate esters are described in U.S. Patent Nos. 4,710,532, 4,789,700, 4,870,204, 4,883,905, 4,892,967, 4,931,583, 4,711,922 and 4,954,649 and are available from the Morflex Chemical Co. of Greensboro, N.C.
In addition to the polyolef:ins and plasticizers described above, other compounds may be included in the plastic composition of the present invention. For example, it may be desired to include a polyolefin copolymer having a lower modulus so as t:o impart still greater flexibility to the plastic composition, enhance the impact strength of the plastic composition and/or improve the bonding bEetween the various compounds of the plastic composition. Thus the plastic composition may include polyolefin copolymers such as block copolymers. As set forth in U.S. Patent . Application Serial No. 08/360,913 filed on December 21, 1994 in the name of Shang et al. and assigned to the assignee of the present application, which is incorporated by reference herein, the block copolymers may either be "functionalized" (i.e. containing a functional group of, for example, malefic anhydride) of "non-functionalized". For example, block copolymers of ethylene and butylene with terminal blocks of styrene may be included. Such polyolefin copolymers are available under the name Kraton from the Shell Chemical Co. Particularly well suited for inclusion in the plastic composition are Kraton G-1924X and Kraton K-1660. Other suitable lblock copolymers are Septon 2007, 4033, 8007, 8006, 1001, 2002, 2043, 2063, 2006, 2104 and 4005 available from Kuraray Corporation of Tokyo, Japan.
In addition, the plastic composition may also include a selected amount of a po:lyamide (such as, for example, nylon). It is believed that inclusion of polyamide such as nylon makes the container more suitable for sealing by radio frequency (RF') energy.
Polyamides are available from many different manufacturers and one particular polyamide that may be used with the plastic composition of thE: present invention is TPX-159 availablE~ from the Henkel Corporation.
The plastic composition may include other compounds useful in manufacture of the plastic composition (and containers made thereof ) and useful for the long term storage of blood cells. For example, as reported in U.S. Patent No. 5,037,415, ( incorporated by reference herein ) , Vitamin E; has been identified as also being capable of suppressing the hemolysis of blood cells. Also, as reported in Laermer et al. "Use of Biological Antioxidants as Propylene stabilizers", Plastics and Rubber Processing and Applicants 14 (1990) 235-239 and Laermer et al.
"Alpha-Tocopherol (Vitamin E) - The natural Antioxidant for Polyolefins "Journal of Plastic Film and Sheeting, Vol. 8, July 1992 (both of which are also incorporated by reference), Vitamin E (which is a mixture of tocopherols and t.ocotrienol:~ ) is an antioxidant that can serve as a stabilizer during extrusion of polyolefins. Vitamin. E as an antioxidant is preferred because, as reported in the 1992 article WO 99/03924 F'C'T/US98/12949 by Laermer, it is non-toxic and is "generally regarded as safe" (GRAS) by the FDA. Of course, other antioxidants (which are also plasticizers) such as epoxidized oil may also be used.
Thus, it is contemplated that one or more of the compounds such as Vitamin E, citrate ester, TEHTM
and/or epoxidized oil may be combined 'with the polyolefin copolymers described above. For example, in one embodiment Vitamin E and B~THC is combined with the polyolefin copolymer. In another embodiment, the amount of BTHC can be reduced and a second plasticizes, such as TEHTM, is combined with Vitamin E and the polyolefin copolymer. Of course, other combinations of the plasticizers, stabilizers and polyolefin copolymers are also possible and within the scope of the present invention. Use of Vitamin E, citrate ester, TEHTM and/or eopoxidized oil with plastic compositions is disclosed in more detail in co-pending patent application entitled "Plastic Compositions Including Vitamin E for Medical Containers and Methods For Providing Such Compositions and Containers", filed simultaneously herewith, in the name of Shaye-wen Shang, which is incorporated by reference herein. Vitamin E is available from several suppliers including Hoffman-La Roche Corporation of Nutley, New Jersey.
Some or all of the above described compounds may be included in the plastic composition of the present invention. For example, anywhere between approximately 30-99%, by weight, of polyolefin copolymer produced, for example, by the Catalloy, Spheripol, Spherilene or other processes may be combined with 0-50%, by weight of another polyolefin copolymer produced by either the C atalloy, Spheripol, Spherilene or other processes. The polyolefin copolymers) are further combined with between 1-50%, by weight, of plasticizes such as a citrate ester. In WO 99/03924 )~'CT/US98/12949 addition, between 0-15%, by weight, of polyamide, and 0-70%, by weight of one or more block copolymers, such as Kraton, may also be included. Finally, the plastic composition may include between ~0-30%, by weight, of Vitamin E (and, if desired, 0-10%, by weight. of TEHTM
and/or 0-15%, by weight of other antioxidants such as epoxodized oil.) In one embodiment, the plastic composition includes between approximately 41J-90%, by weight, of Catalloy polyolefin copolymer, approximately 5-30%, by weight, of a Spheripol polyolefin copolymer, approximately 5-10%, by weight, polyamide, approximately 5-10%, by weight of a first block copolymer such as G-1924X, between approximately 10-30%, by weight, of a second bloc)c copolymer, such as Kraton-1660, between approximately 5-30%, b;y weight, of a citrate ester, such as ;n-butyryltri-n-hexyl citrate and between approximately 0-5%, by weight of Vitamin E. Additional formulations A-E embodying the present invention are set forth in Table 1. The amounts of the different polymers and compounds are expressed as percentages (by weight) of the plastic composition.
WO 99/03924 F'CTNS98/12949 i o o o m ~
vo n 'r' w y f~ N
tl1 W dP O ~ ~
1~ , O
N
x O O O
O ~
O 1f~~"1 N
H
H
U ~ o O o o~
O
x H
as ~ ~ ~n ~ c~ w H
H
O
CL
dP y n ~ ~ ~ o V
H
H W
N
~ ff C9 i , ~ ~ o o tl1~ ~ N 10 o OD I 01 ~DU b ~
i t%~~ ~ 1 1 H
-r c~ x v~ H c~ e~a~
a ~
f-1~ N
.>v~ T7 -~-IN
r--Ir-ifC O ~ ~ ~rl ro ro~ 'b o ~o o o s~ h ~
W U U f~ a4 a4t~ ~tl~
s~
W ~-1~ !C
rl r-1r-1r-I ~ U
.-IG7 O ~ .-~r-ir~ O
G~ ~ ~ x ~ ~--Iw ix cv a c c a~ n~h 0 o a~ .c .~o ~a cn ~ ~ x cn cn~
SUBSTTTUTE SHEET (RUILE 26) Medical containers made in accordance with the present invention may be prepared by mixing the above described components in approximately the above described amounts in a large scale mixer. The polyolefin copolymers and plasticizes are mi~:ed for anywhere between 1 to 30 minutes and, most typically, approximately 5 minutes. Other components described above rnay be added to the composition and the entire blend may be extruded, in ways that are known to those skilled in the art, to form small pellets. The pellets may be further blended and/or formed into plastic sheets ranging in thickness between 5 and 20 mils and, preferably, 5 to 15 mils. The plastic sheets are then brought together in face to face relationship, shaped into containers, inserted with tubing ports (which may be .made of the plastic composition or any other steam sterilizable plastic composition) in ways that are known to those of skill in the art. The sheets of formed plastic material are then sealed by, for example, RF sealing and sterilized by steam or other form of sterilization.
Figs. 3-5 show the ability of the plastic composition to retain plasticizes during steam sterilization. The formulations set forth in Table 1 (using different amounts of the above described compounds) were prepared and made into containers generally in accordance with the rrcethod described above.
The amount of plasticizes was measured (by FTIR
spectroscopy) in each formulation before, after 20 minutes, and after 60 minutes of steam sterilization at approximately 120C. The results of the measurements are set forth in Figs. 3-5.
As seen in Figs. 3-5 (and particularly, Figs. 4 and 5), plastic compositions of the present invention are able to retain most of the original plastic.izer (BTHC) even after exposure to a sterilizing temperature ( a . g .
120C) for 60 minutes. For example, the area of the BTHC
peak (at about 1730 cm') in each sample is not WO 99/03924 fCT/US98/12949 substantially changed at 20 and/or at 60 minutes (Figs.
4 and 5 respectively) of sterilization as compared to before sterilization (Fig. 3).
. The above description is intended for illustrative purposes only and is not intended to limit the present invention to any one of the embodiments described above.
The true scope of the present invention is defined by the claims set forth below.
Alternatively, two or more of the above polyolefins and/or copolymers thereof may be combined. For example, in one embodiment, both KS-051P and SA-8495 polyolefin copolymers may be used in the' plastic composition. It should be understood that the above described Catalloy and Spheripol polymers are available in a non-porous pellet and porous spherical forms. In the plastic composition of the present invention, it is preferred that at least one of the copolymers is of the porous spherical variety so as to better adsorb the plasticizes.
The polyolefin or polyolefin copolymers described above may be combined with a selected amaunt of a suitable plasticizes and/or other material that is capable of suppressing the hemolysis of r_ed blood cells. A plasticizes compatible with the polyolefin copolymer (that is, capable of being mixed and compounded with the polyolefin copolymer and being retained by the polyolefin copolymer during heating ) is preferred. Plasticizers capable of being' combined with the polyolefin copolymers described above include, but are not limited to, DEHP, TEHTM and, preferably, citrate esters. Of course, other known materials capable of suppressing hemolysis may also be used. Preferably citrate esters of the formula CHI COOR, R, COOC-COORz where : R" R2 and R3 = CHj to C,BH3, and R, = CH3 to C,Hls may be combined with the po.lyolefin copolymers described above. For example, citrate esters such as acetyltri-n-hexyl citrate, n-butyryltri-n-hexyl citrate, acetyltri-n-(hexyl/octyl/decyl/citrate or acetyltri-n-(octyl/decyl) citrate are suitable and n-butyryltri-n-hexyl citrate (sorrel=imes abbreviated as BTHC) is preferred. Such citrate esters are described in U.S. Patent Nos. 4,710,532, 4,789,700, 4,870,204, 4,883,905, 4,892,967, 4,931,583, 4,711,922 and 4,954,649 and are available from the Morflex Chemical Co. of Greensboro, N.C.
In addition to the polyolef:ins and plasticizers described above, other compounds may be included in the plastic composition of the present invention. For example, it may be desired to include a polyolefin copolymer having a lower modulus so as t:o impart still greater flexibility to the plastic composition, enhance the impact strength of the plastic composition and/or improve the bonding bEetween the various compounds of the plastic composition. Thus the plastic composition may include polyolefin copolymers such as block copolymers. As set forth in U.S. Patent . Application Serial No. 08/360,913 filed on December 21, 1994 in the name of Shang et al. and assigned to the assignee of the present application, which is incorporated by reference herein, the block copolymers may either be "functionalized" (i.e. containing a functional group of, for example, malefic anhydride) of "non-functionalized". For example, block copolymers of ethylene and butylene with terminal blocks of styrene may be included. Such polyolefin copolymers are available under the name Kraton from the Shell Chemical Co. Particularly well suited for inclusion in the plastic composition are Kraton G-1924X and Kraton K-1660. Other suitable lblock copolymers are Septon 2007, 4033, 8007, 8006, 1001, 2002, 2043, 2063, 2006, 2104 and 4005 available from Kuraray Corporation of Tokyo, Japan.
In addition, the plastic composition may also include a selected amount of a po:lyamide (such as, for example, nylon). It is believed that inclusion of polyamide such as nylon makes the container more suitable for sealing by radio frequency (RF') energy.
Polyamides are available from many different manufacturers and one particular polyamide that may be used with the plastic composition of thE: present invention is TPX-159 availablE~ from the Henkel Corporation.
The plastic composition may include other compounds useful in manufacture of the plastic composition (and containers made thereof ) and useful for the long term storage of blood cells. For example, as reported in U.S. Patent No. 5,037,415, ( incorporated by reference herein ) , Vitamin E; has been identified as also being capable of suppressing the hemolysis of blood cells. Also, as reported in Laermer et al. "Use of Biological Antioxidants as Propylene stabilizers", Plastics and Rubber Processing and Applicants 14 (1990) 235-239 and Laermer et al.
"Alpha-Tocopherol (Vitamin E) - The natural Antioxidant for Polyolefins "Journal of Plastic Film and Sheeting, Vol. 8, July 1992 (both of which are also incorporated by reference), Vitamin E (which is a mixture of tocopherols and t.ocotrienol:~ ) is an antioxidant that can serve as a stabilizer during extrusion of polyolefins. Vitamin. E as an antioxidant is preferred because, as reported in the 1992 article WO 99/03924 F'C'T/US98/12949 by Laermer, it is non-toxic and is "generally regarded as safe" (GRAS) by the FDA. Of course, other antioxidants (which are also plasticizers) such as epoxidized oil may also be used.
Thus, it is contemplated that one or more of the compounds such as Vitamin E, citrate ester, TEHTM
and/or epoxidized oil may be combined 'with the polyolefin copolymers described above. For example, in one embodiment Vitamin E and B~THC is combined with the polyolefin copolymer. In another embodiment, the amount of BTHC can be reduced and a second plasticizes, such as TEHTM, is combined with Vitamin E and the polyolefin copolymer. Of course, other combinations of the plasticizers, stabilizers and polyolefin copolymers are also possible and within the scope of the present invention. Use of Vitamin E, citrate ester, TEHTM and/or eopoxidized oil with plastic compositions is disclosed in more detail in co-pending patent application entitled "Plastic Compositions Including Vitamin E for Medical Containers and Methods For Providing Such Compositions and Containers", filed simultaneously herewith, in the name of Shaye-wen Shang, which is incorporated by reference herein. Vitamin E is available from several suppliers including Hoffman-La Roche Corporation of Nutley, New Jersey.
Some or all of the above described compounds may be included in the plastic composition of the present invention. For example, anywhere between approximately 30-99%, by weight, of polyolefin copolymer produced, for example, by the Catalloy, Spheripol, Spherilene or other processes may be combined with 0-50%, by weight of another polyolefin copolymer produced by either the C atalloy, Spheripol, Spherilene or other processes. The polyolefin copolymers) are further combined with between 1-50%, by weight, of plasticizes such as a citrate ester. In WO 99/03924 )~'CT/US98/12949 addition, between 0-15%, by weight, of polyamide, and 0-70%, by weight of one or more block copolymers, such as Kraton, may also be included. Finally, the plastic composition may include between ~0-30%, by weight, of Vitamin E (and, if desired, 0-10%, by weight. of TEHTM
and/or 0-15%, by weight of other antioxidants such as epoxodized oil.) In one embodiment, the plastic composition includes between approximately 41J-90%, by weight, of Catalloy polyolefin copolymer, approximately 5-30%, by weight, of a Spheripol polyolefin copolymer, approximately 5-10%, by weight, polyamide, approximately 5-10%, by weight of a first block copolymer such as G-1924X, between approximately 10-30%, by weight, of a second bloc)c copolymer, such as Kraton-1660, between approximately 5-30%, b;y weight, of a citrate ester, such as ;n-butyryltri-n-hexyl citrate and between approximately 0-5%, by weight of Vitamin E. Additional formulations A-E embodying the present invention are set forth in Table 1. The amounts of the different polymers and compounds are expressed as percentages (by weight) of the plastic composition.
WO 99/03924 F'CTNS98/12949 i o o o m ~
vo n 'r' w y f~ N
tl1 W dP O ~ ~
1~ , O
N
x O O O
O ~
O 1f~~"1 N
H
H
U ~ o O o o~
O
x H
as ~ ~ ~n ~ c~ w H
H
O
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dP y n ~ ~ ~ o V
H
H W
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~ ff C9 i , ~ ~ o o tl1~ ~ N 10 o OD I 01 ~DU b ~
i t%~~ ~ 1 1 H
-r c~ x v~ H c~ e~a~
a ~
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.>v~ T7 -~-IN
r--Ir-ifC O ~ ~ ~rl ro ro~ 'b o ~o o o s~ h ~
W U U f~ a4 a4t~ ~tl~
s~
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rl r-1r-1r-I ~ U
.-IG7 O ~ .-~r-ir~ O
G~ ~ ~ x ~ ~--Iw ix cv a c c a~ n~h 0 o a~ .c .~o ~a cn ~ ~ x cn cn~
SUBSTTTUTE SHEET (RUILE 26) Medical containers made in accordance with the present invention may be prepared by mixing the above described components in approximately the above described amounts in a large scale mixer. The polyolefin copolymers and plasticizes are mi~:ed for anywhere between 1 to 30 minutes and, most typically, approximately 5 minutes. Other components described above rnay be added to the composition and the entire blend may be extruded, in ways that are known to those skilled in the art, to form small pellets. The pellets may be further blended and/or formed into plastic sheets ranging in thickness between 5 and 20 mils and, preferably, 5 to 15 mils. The plastic sheets are then brought together in face to face relationship, shaped into containers, inserted with tubing ports (which may be .made of the plastic composition or any other steam sterilizable plastic composition) in ways that are known to those of skill in the art. The sheets of formed plastic material are then sealed by, for example, RF sealing and sterilized by steam or other form of sterilization.
Figs. 3-5 show the ability of the plastic composition to retain plasticizes during steam sterilization. The formulations set forth in Table 1 (using different amounts of the above described compounds) were prepared and made into containers generally in accordance with the rrcethod described above.
The amount of plasticizes was measured (by FTIR
spectroscopy) in each formulation before, after 20 minutes, and after 60 minutes of steam sterilization at approximately 120C. The results of the measurements are set forth in Figs. 3-5.
As seen in Figs. 3-5 (and particularly, Figs. 4 and 5), plastic compositions of the present invention are able to retain most of the original plastic.izer (BTHC) even after exposure to a sterilizing temperature ( a . g .
120C) for 60 minutes. For example, the area of the BTHC
peak (at about 1730 cm') in each sample is not WO 99/03924 fCT/US98/12949 substantially changed at 20 and/or at 60 minutes (Figs.
4 and 5 respectively) of sterilization as compared to before sterilization (Fig. 3).
. The above description is intended for illustrative purposes only and is not intended to limit the present invention to any one of the embodiments described above.
The true scope of the present invention is defined by the claims set forth below.
Claims (65)
1. A flexible, plastic composition comprising:
a polyolefin copolymer;
a plasticizer;
said composition having a flexibility that is substantially unchanged upon heating to a sterilizing temperature relative to said flexibility before said heating.
a polyolefin copolymer;
a plasticizer;
said composition having a flexibility that is substantially unchanged upon heating to a sterilizing temperature relative to said flexibility before said heating.
2. The plastic composition of Claim 1 wherein said polyolefin copolymer comprises a polypropylene copolymer.
3. The plastic composition of Claim 1 further comprising a second polyolefin copolymer.
4. The plastic composition of Claim 3 wherein said second polyolefin copolymer comprises a polypropylene copolymer.
5. The plastic composition of Claim 1 comprising by weight of said composition:
between approximately 30%-99% of a polypropylene copolymer;
between approximately 1%-50% of said plasticizer.
between approximately 30%-99% of a polypropylene copolymer;
between approximately 1%-50% of said plasticizer.
6. The plastic composition of Claim 4 comprising by weight of said composition:
between approximately 50%-95% of said first polypropylene copolymer;
between approximately 4%-49% of said second polypropylene copolymer;
between approximately 1%-30% of said plasticizer.
between approximately 50%-95% of said first polypropylene copolymer;
between approximately 4%-49% of said second polypropylene copolymer;
between approximately 1%-30% of said plasticizer.
7. The plastic composition of Claim 1 further comprising a block copolymer.
8. The plastic composition of Claim 1 further comprising a polyamide.
9. The plastic composition of Claim 1 further comprising a stabilizer.
10. The plastic composition of Claim 1 comprising, by weight of said composition:
between approximately 30-80% of a first polypropylene copolymer;
between approximately 5%-30% of a second polypropylene copolymer;
between approximately 0%-15% of a polyamide;
between approximately 0%-20% of a first block copolymer;
between approximately 0%-50% of a second block copolymer; and between approximately 1%-40% of a plasticizer;
and between approximately 0%-5% of a stabilizer.
between approximately 30-80% of a first polypropylene copolymer;
between approximately 5%-30% of a second polypropylene copolymer;
between approximately 0%-15% of a polyamide;
between approximately 0%-20% of a first block copolymer;
between approximately 0%-50% of a second block copolymer; and between approximately 1%-40% of a plasticizer;
and between approximately 0%-5% of a stabilizer.
11. The plastic composition of Claim 1 wherein said plasticizes comprises a citrate ester.
12. The plastic composition of Claim 11 wherein said citrate ester is n-butyryltri-n-hexyl citrate.
13. The plastic composition wherein said polyolefin is capable of retaining at least 50% of said plasticizes.
14. The plastic composition of Claim 1 wherein said polyolefin copolymer is capable of retaining and effective amount of plasticizer after heating at approximately 120°C for at least 20 minutes.
15. The plastic composition of Claim 1 wherein said polyolefin copolymer is capable of retaining and effective amount of plasticizer after heating at approximately 120°C for at least 60 minutes.
16. The plastic composition of Claim 10 wherein said first block copolymer is non-functionalized and comprises a central block of ethylene and butylene and terminal blocks of styrene and said second block copolymer is functionalized and comprises a central block of ethylene and butylene and terminal blocks of styrene.
17. The plastic composition of Claim 9 wherein said stabilizer comprises Vitamin E.
18. The composition of Claim 1 wherein said polyolefin comprises a porous polypropylene copolymer and said plasticizes comprises a citrate ester.
19. The composition of Claim 17 wherein said polyolefin copolymer is a copolymer of propylene and at least one monomer selected from the group of ethylene and butylene.
20. A flexible, plastic container having a wall, wherein at least a portion of the wall interior surface is made of a plastic composition, said plastic composition comprising:
a polyolefin copolymer;
a plasticizer;
said container having a flexibility that is substantially unchanged upon heating to a sterilizing temperature relative to said flexibility before such heating.
a polyolefin copolymer;
a plasticizer;
said container having a flexibility that is substantially unchanged upon heating to a sterilizing temperature relative to said flexibility before such heating.
21. The container of Claim 20 wherein said plasticizer is capable of contacting blood cells stored therein to suppress hemolysis.
22. The container of Claim 20 wherein said wall is defined by a plurality of plastic layers and at least a portion of said layer in contact with said blood cells comprises said plastic composition.
23. The container of Claim 20 wherein said polyolefin copolymer comprises a polypropylene copolymer.
24. The container of Claim 20 wherein said composition further comprises a second polyolefin copolymer.
25. The container of Claim 20 wherein said second polyolefin copolymer comprises a polypropylene copolymer.
26. The container of Claim 20 wherein said composition comprises, by weight:
between approximately 50%-99% of a polypropylene copolymer;
between approximately 1%-50% of said plasticizer.
between approximately 50%-99% of a polypropylene copolymer;
between approximately 1%-50% of said plasticizer.
27. The container of Claim 20 wherein said composition comprises by weight:
between approximately 50%-95% of said first polypropylene copolymer;
between approximately 4%-49% of said second polypropylene copolymer;
between approximately 1%-30% of said plasticizer.
between approximately 50%-95% of said first polypropylene copolymer;
between approximately 4%-49% of said second polypropylene copolymer;
between approximately 1%-30% of said plasticizer.
28. The container of Claim 20 wherein said composition further comprises a first non-functionalized block copolymer and a second functionalized block copolymer.
29. The container of Claim 20 wherein said composition further comprises a polyamide.
30. The container Claim 20 wherein said composition further comprises a stabilizer.
31. The container of Claim 20 wherein said composition comprises, by weight:
between approximately 30-80% of a first polypropylene copolymer;
between approximately 5%-30% of a second polypropylene copolymer;
between approximately 0%-20% of a polyamide;
between approximately 0%-20% of a first block copolymer;
between approximately 0%-50% of a second block copolymer; and between approximately 1%-40% of a plasticizer;
and between approximately 0%-5% of a stabilizer.
between approximately 30-80% of a first polypropylene copolymer;
between approximately 5%-30% of a second polypropylene copolymer;
between approximately 0%-20% of a polyamide;
between approximately 0%-20% of a first block copolymer;
between approximately 0%-50% of a second block copolymer; and between approximately 1%-40% of a plasticizer;
and between approximately 0%-5% of a stabilizer.
32. The container of Claim 20 wherein said plasticizer comprises a citrate ester.
33. The container of Claim 20 wherein said citrate ester is n-butyryl hexyl citrate.
34. The container of Claim 20 wherein said polyolefin is capable of retaining at least 50% of said plasticizer.
35. The container of Claim 20 wherein said polyolefin copolymer is capable of retaining and effective amount of plasticizes after heating at approximately 120°C for at least 20 minutes.
36. The container of Claim 20 wherein said polyolefin copolymer is capable of regaining and effective amount of plasticizer after heating at approximately 120°C for at least 60 minutes.
37. The container of Claim 20 wherein said first block copolymer comprises a central block of ethylene and butylene and terminal blocks of styrene.
38. The container of Claim 20 wherein said stabilizer comprises Vitamin E.
39. The container of Claim 30 wherein said polyolefin comprises a porous polypropylene copolymer and said plasticizes comprises a citrate ester.
40. The container of Claim 20 wherein said polyolefin copolymer comprises propylene and ethylene units.
41. The container of Claim 20 wherein the thickness of said container wall is between approximately 5-18 mils.
42. A method for providing a blood storage container comprising:
providing a first polyolefin;
combining a plasticizes with said polyolefin to form a plastic composition;
forming sheets of said plastic composition;
forming a container from said sheets; and sterilizing said container;
whereby the flexibility said container remains substantially unchanged upon heating to a sterilizing temperature relative to said flexibility before such heating.
providing a first polyolefin;
combining a plasticizes with said polyolefin to form a plastic composition;
forming sheets of said plastic composition;
forming a container from said sheets; and sterilizing said container;
whereby the flexibility said container remains substantially unchanged upon heating to a sterilizing temperature relative to said flexibility before such heating.
43. The method of Claim 42 further comprising adding a second polyolefin copolymer.
44. The method of Claim 42 further comprising adding a third polyolefin copolymer.
45. The method of Claim 42 further comprising adding a polyamide.
46. The method of Claims 43, 44 or 45 wherein said second polyolefin copolymer, third polyolefin copolymer and polyamide are added after combining said plasticizer with said first polyolefin copolymer.
47. The method of Claims 43, 44 or 45 wherein said second polyolefin copolymer, third polyolefin copolymer and polyamide are added before combining said plasticizer with said first polyolefin copolymer.
48. The method of Claim 42 further comprising forming pellets of said plastic composition.
49. The method of Claim 42 wherein said container is sterilized by steam sterilization.
50. The method of Claim 49 wherein said container is steam sterilized at approximately 120°C for at least 20 minutes.
51. The method of Claim 43 wherein at least one of said polyolefin copolymers is in porous powder form.
52. The method of Claim 42 comprising providing a first polyolefin copolymer comprising propylene units.
53. The method of Claim 52 wherein said polyolefin copolymer comprises propylene and ethylene units.
54. The method of Claim 42 comprising providing a first polyolefin copolymer in powder form.
55. The method of Claim 42 comprising combining:
between approximately 30-80% of a first polypropylene copolymer;
between approximately 5%-30% of a second polypropylene copolymer;
between approximately 0%-15% of a polyamide;
between approximately 0%-20% of a first block copolymer;
between approximately 0%-50% of a second block copolymer; and between approximately 1%-40% of a plasticizer;
and between approximately 0%-5% of a stabilizer.
between approximately 30-80% of a first polypropylene copolymer;
between approximately 5%-30% of a second polypropylene copolymer;
between approximately 0%-15% of a polyamide;
between approximately 0%-20% of a first block copolymer;
between approximately 0%-50% of a second block copolymer; and between approximately 1%-40% of a plasticizer;
and between approximately 0%-5% of a stabilizer.
56. The method of Claim 42 wherein the amount of plasticizer in the plastic composition after said sterilizing step is substantially the same as the amount of plasticizer remaining in said plastic composition after immediately after sterilization.
57. The method of Claim 42 further comprising adding an antioxidant.
58. The method of Claim 57 wherein said antioxidant and plasticizer are combined before said plasticizer is combined with said polyolefin.
59. The method of Claim 58 wherein said antioxidant is Vitamin E.
60. The method of Claim 42 wherein said container is sterilized by gamma radiation.
61. The method of Claim 42 wherein said container is sterilized by exposure to ethylene oxide.
62. The method of Claim 43 wherein at least one of said polyolefin copolymers is in pellet form.
63. A method for storing blood cells comprising:
providing a flexible plastic container having at least a portion of its interior surface formed of a plastic composition comprising a polyolefin copolymer and a plasticizer, wherein the flexibility of said plastic composition remains substantially unchanged upon heating to a sterilizing temperature relative to said flexibility before such heating;
introducing a quantity of blood cells into said container; and maintaining said quantity of blood cells within said container;
providing a flexible plastic container having at least a portion of its interior surface formed of a plastic composition comprising a polyolefin copolymer and a plasticizer, wherein the flexibility of said plastic composition remains substantially unchanged upon heating to a sterilizing temperature relative to said flexibility before such heating;
introducing a quantity of blood cells into said container; and maintaining said quantity of blood cells within said container;
64. The method of Claim 63 wherein said plastic composition comprises a polypropylene copolymer and a citrate ester.
65. The method of Claim 63 comprising providing a flexible plastic container having at least a portion of its interior surface formed of a plastic composition comprising:
a first polyolefin copolymer;
a second polyolefin copolymer; and a citrate ester.
a first polyolefin copolymer;
a second polyolefin copolymer; and a citrate ester.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/897,042 US5952423A (en) | 1997-07-18 | 1997-07-18 | Plastic compositions for medical containers and methods for providing such containers and for storing red blood cells |
| US08/897,042 | 1997-07-18 | ||
| PCT/US1998/012949 WO1999003924A1 (en) | 1997-07-18 | 1998-06-22 | Plastic compositions for medical containers and methods for providing such containers and for storing red blood cells |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2296367A1 true CA2296367A1 (en) | 1999-01-28 |
Family
ID=25407266
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002296367A Abandoned CA2296367A1 (en) | 1997-07-18 | 1998-06-22 | Plastic compositions for medical containers and methods for providing such containers and for storing red blood cells |
Country Status (7)
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|---|---|
| US (1) | US5952423A (en) |
| EP (1) | EP0996677B1 (en) |
| AU (1) | AU736086B2 (en) |
| CA (1) | CA2296367A1 (en) |
| DE (1) | DE69809554T2 (en) |
| NZ (1) | NZ502009A (en) |
| WO (1) | WO1999003924A1 (en) |
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|---|---|---|---|---|
| US6468258B1 (en) | 1997-07-18 | 2002-10-22 | Baxter International Inc. | Plastic compositions including vitamin E for medical containers and methods for providing such compositions and containers |
| US6615835B1 (en) * | 1999-09-20 | 2003-09-09 | Ballard Medical Products | Flexible multiple port adaptor |
| US7691645B2 (en) | 2001-01-09 | 2010-04-06 | Agilent Technologies, Inc. | Immunosubtraction method |
| CA2436175A1 (en) * | 2001-02-20 | 2002-08-29 | Pall Corporation | Container for biological fluid |
| US20070031812A1 (en) * | 2003-06-20 | 2007-02-08 | Pall Corporation | Processing of platelet-containing biological fluids |
| US20050085785A1 (en) * | 2003-10-17 | 2005-04-21 | Sherwin Shang | High impact strength film and non-pvc containing container and pouch and overpouch |
| US7353827B2 (en) * | 2004-09-01 | 2008-04-08 | Vitol Signs, Inc. | Mask, mask shell and seal with improved mounting, mask seal, method of mask manufacture and mask with reduced exhalation noise |
| US9725202B2 (en) | 2013-03-14 | 2017-08-08 | Berry Plastics Corporation | Container |
| TW201512274A (en) | 2013-07-12 | 2015-04-01 | Berry Plastics Corp | Polymeric material for container |
| MX2016002374A (en) | 2013-08-26 | 2016-05-31 | Berry Plastics Corp | Polymeric material for container. |
| TW201532782A (en) | 2013-08-30 | 2015-09-01 | Berry Plastics Corp | Container and process for making the same |
| WO2016141179A1 (en) | 2015-03-04 | 2016-09-09 | Berry Plastics Corporation | Polymeric material for container |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4140162A (en) * | 1977-07-28 | 1979-02-20 | Baxter Travenol Lab | Clear, autoclavable plastic formulation free of liquid plasticizers |
| US4710532A (en) * | 1985-03-13 | 1987-12-01 | Morflex Chemical Company, Inc. | Medical article and method |
| US4883905A (en) * | 1984-06-11 | 1989-11-28 | Morflex Chemical Company, Inc. | Process for preparing citrates using organic titanates |
| US4789700A (en) * | 1984-06-11 | 1988-12-06 | Morflex Chemical Company, Inc. | Citrate esters and method |
| US4870204A (en) * | 1984-06-11 | 1989-09-26 | Morflex Chemical Company, Inc. | Method for preparing citrate esters |
| US4711922A (en) * | 1985-05-17 | 1987-12-08 | Morflex Chemical Company, Inc. | Citrate esters and methods |
| US4824893A (en) * | 1984-06-11 | 1989-04-25 | Morflex Chemical Company, Inc. | Citrate esters and methods |
| US4892967A (en) * | 1984-06-11 | 1990-01-09 | Morflex Chemical Company, Inc. | Citrate esters |
| US4954649A (en) * | 1984-06-11 | 1990-09-04 | Morflex Chemical Company, Inc. | Method for producing citrates |
| US4931583A (en) * | 1984-06-11 | 1990-06-05 | Morflex Chemical Compay, Inc. | Citrate esters |
| US5167657A (en) * | 1988-11-14 | 1992-12-01 | Baxter International Inc. | Plastic composition with anti-hemolytic effect |
| US5100401A (en) * | 1988-11-14 | 1992-03-31 | Baxter International Inc. | Plastic composition with anti-hemolytic effect |
| US5026347A (en) * | 1988-11-14 | 1991-06-25 | Baxter International Inc. | Plastic composition with anti-hemolytic effect |
| IT1230133B (en) * | 1989-04-28 | 1991-10-14 | Himont Inc | PLASTIC-ELASTIC POLYPROPYLENE COMPOSITIONS |
| US5037419A (en) * | 1989-09-21 | 1991-08-06 | Eastman Kodak Company | Blood bag system containing vitamin E |
| JP3251601B2 (en) * | 1991-01-30 | 2002-01-28 | テルモ株式会社 | Blood bags and medical tubes |
| IT1262934B (en) * | 1992-01-31 | 1996-07-22 | Montecatini Tecnologie Srl | COMPONENTS AND CATALYSTS FOR THE POLYMERIZATION OF OLEFINE |
| US5482772A (en) * | 1992-12-28 | 1996-01-09 | Kimberly-Clark Corporation | Polymeric strands including a propylene polymer composition and nonwoven fabric and articles made therewith |
| IT1271425B (en) * | 1993-01-13 | 1997-05-28 | Himont Inc | COMPONENTS AND CATALYSTS FOR THE POLYMERIZATION OF ETHYLENE |
| TW325482B (en) * | 1994-01-31 | 1998-01-21 | Himont Inc | A process for sequentially grafting olefin polymer materials and grafted polymer therefrom |
| IT1273660B (en) * | 1994-07-20 | 1997-07-09 | Spherilene Srl | PROCEDURE FOR THE PREPARATION OF AMORPHOUS PROPYLENE POLYMERS |
| US5683768A (en) * | 1994-12-21 | 1997-11-04 | Baxter International Inc. | Plastic formulations for platelet storage containers and the like |
| US5585434A (en) * | 1995-05-31 | 1996-12-17 | Montell North America Inc. | Blends of polyolefin graft copolymers and polycarbonate |
-
1997
- 1997-07-18 US US08/897,042 patent/US5952423A/en not_active Expired - Lifetime
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- 1998-06-22 WO PCT/US1998/012949 patent/WO1999003924A1/en active IP Right Grant
- 1998-06-22 CA CA002296367A patent/CA2296367A1/en not_active Abandoned
- 1998-06-22 DE DE69809554T patent/DE69809554T2/en not_active Expired - Fee Related
- 1998-06-22 EP EP98931465A patent/EP0996677B1/en not_active Expired - Lifetime
- 1998-06-22 NZ NZ502009A patent/NZ502009A/en unknown
- 1998-06-22 AU AU81589/98A patent/AU736086B2/en not_active Ceased
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| DE69809554T2 (en) | 2003-10-02 |
| AU8158998A (en) | 1999-02-10 |
| WO1999003924A1 (en) | 1999-01-28 |
| AU736086B2 (en) | 2001-07-26 |
| NZ502009A (en) | 2001-12-21 |
| EP0996677A1 (en) | 2000-05-03 |
| EP0996677B1 (en) | 2002-11-20 |
| US5952423A (en) | 1999-09-14 |
| DE69809554D1 (en) | 2003-01-02 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |