US3576650A - Cryogenic plastic film package - Google Patents

Abstract

A PLASTIC FILM PACKAGE FABRICATED FROM A BIAXIALLY ORIENTED POLYOLEFIN FILM OBTAINED FROM A RESIN COMPOSITION COMPRISING EITHER A HOMOPOLYMER AND/OR A COPOLYMER OF AT LEAST ABOUT 50% BY WEIGHT OF ETHYLENE IS UTILIZED FOR PACKAGING VIABLE AND PERSIHABLE MATERIALS THEREIN AT CRYOGENIC TEMPERATURES.

Description

April 27, 1971 w, UNDERWOOD ETAL 3,576,650

CRYOGENIC PLASTIC FILM PACKAGE Filed Jan. 18, 1968 Collection Tubes Tubes w E O G M mmw W ww fu F R w Ym do NAEL T K T LN 1A mm WSF 3,576,650 CRYOGENIC PLASTIC FILM PACKAGE William F. Underwood, Oak Park, and Stanley Lustig, Park Forest, Ill., and Franklin E. Schrage, Princeton, N.J., assignors to Union Carbide Corporation Filed Jan. 18, 1968, Ser. No. 698,771 Int. Cl. A23b 7/04; B65d 85/50 U.S. Cl. 99-171 Claims ABSTRACT OF THE DISCLOSURE A plastic film package fabricated from a biaxially oriented polyolefin film obtained from a resin composition comprising either a homopolymer and/or a copolymer of at least about 50% by weight of ethylene is utilized for packaging viable and perishable materials therein at cryogenic temperatures.

This invention relates to a plastic film package for perishable and/or viable materials stored at cryogenic temperatures. More particularly, this invention relates to a biaxially oriented polyolefin film as the plastic film utilized to package, preserve and maintain perishable and/or viable materials at cryogenic temperatures. Even more particularly this invention relates to a plastic film package for storing and maintaining blood, blood platelets, and other components of blood as well as human and animal organs, tissues and the like at cryogenic temperatures.

The packaging and preservation of blood, blood platelets, other components of blood and the like at cryogenic temperatures for furture use has been heretofore achieved with some degree of success. The packaging materials employed in these endeavors, however, have not been completely satisfactory or acceptable. Durable materials such as stainless steel, aluminum and the like have generally been employed for the preservation of whole blood, blood platelets and the like at cryogenic temperatures and have proven to be quite costly and inefiicient.

Fresh blood can be safely stored at refrigerator temperatures of about 4 C., for a period of only 21 days, while platelets become outdated within a few hours. In order to store blood for prolonged periods, the plasma is separated from the blood cells and other components by centrifugation. The plasma is then stored at refrigerator temperatures of about 4 C., or freeze-dried. The blood cells, platelets, leukocytes, and other components of blood are then treated with a low-temperature preservative such as glycerol, dimethyl sulfoxide, or polyvinyl pyrollidone and then frozen and stored in plastic containers at temperatures as low as -80 C, This temperature (80 C.) is the lowest temperature at which present plastic containers perform satisfactorily. But even at this temperature the blood cells, platelets, leukocytes, etc. undergo gradual undesirable changes. On the other hand, when maintained at cryogenic temperatures such as that of liquid nitrogen (-l96- C.) red blood cells may be stored for periods of use and the other com- United States Patent 0 ice ponents of blood can be stored at these temperatures for greatly extended periods. At present, metal containers are the only satisfactory containers which can be used to store these components at cryogenic temperatures in the vicinity of liquid nitrogen.

It is an object of this invention, therefore, to provide a plastic film package for the preservation and maintenance of viable and/or perishable substances for prolonged periods of time at cryogenic temperatures and from which these viable and/or perishable materials can be readily recovered for subsequent use.

This and other objects of the invention will become more apparent from the ensuing discussion.

The figure shows a plastic film package having heat seals and tubing for collection of blood therein.

It has been found that the objects of the present invention can be generally obtained by providing a biaxially oriented polyolefin film for use as the plastic film package for storing viable and/or perishable substances for prolonged periods of time at cryogenic temperatures and down to at least the temperature of liquid nitrogen (196 C.).

The films that have been found useful to accomplish the objects of the present invention can be generally described as biaxially oriented polyolefin films whose major polymeric constituent; that is, an amount greater than about 50% by weight, is ethylene, As is well known to those skilled in the art, these polyolefin resins can be homopolymers or can be copolymerized with other comonomers such as acrylic acid, methylacrylic acid, vinyl acetate, ethyl acrylate, propylene, butylene, neo hexene and the like. To obtain films which will exhibit exceptional durability, flexibility and strong heat seals at low temperatures, it is preferred that the film be fabricated from an ethylene homopolymer resin.

It has been found that in order to be effective for use as a packaging material at cryogenic temperatures for prolonged periods of time, the resins from which the polyolefin films of the invention are obtained must have an intrinsic viscosity of at least about 1.2 and the films must be biaxially oriented at temperatures below their crystalline melting points to at least about 300% in the machine direction and the transverse direction. For example, when biaxially orienting a film obtained from a low density polyethylene homopolymer resin, it is pre ferred to regulate and control the temperature of the film so that it is below its crystalline melting point during biaxial orientation.

Fabricating the plastic films of this invention in this manner has been found to yield plastic films which possess and exhibit the desired and required properties and characteristics for their use as a packaging material at cryogenic temperatures. Hence, the plastic fihns of this invention exhibit and possess such desirable properties as good flexibility without cracking, being readily heat-scalable, durable seals, sterility, low fabricating costs, and the like.

The biaxially oriented polyolefin films which can be utilized in the practice of this invention can be obtained from extrusion methods and apparatus well known to those skilled in the art. For example, any conventional dry blending and extrusion techniques can be employed to obtain tubular films which can then be subsequently biaxially oriented.

Preferably, the double-bubble process is used to produce these biaxially oriented films. In this process a primary tube is first formed by melt extrusion from a die, inflated by the admission of air, cooled, collapsed, and then reinflated to form an isolated bubble, and the tub ing is advanced through a heating zone to raise the film to its draw temperature. In the draw or expansion zone the film is radially expanded in both the transverse and machine directions at a temperature such that orientation occurs in both directions, the expansion of the tubing'being accompanied by a sharp, sudden reduction of thickness at the draw point. T o obtain the films of this invention, this secondary bubble should be subjected to stretching of a magnitude of at least about 300% in the machine and transverse directions. The preferred draw temperature is 15 F. to 50 F. below the crystalline melting point of the resin. Alternatively, the well known tentering techniques may be employed for biorientation of the films obtained in sheet form.

To obtain resins or bioriented films which will exhibit the required minimum intrinsic viscosity, direct polymerization of the resin components to the required intrinsic viscosity is preferred. Alternatively, the resins or films can be subjected to mechanical cross-linking techniques, such as irradiation or be subjected to chemical treatments, such as employing an oxidizing agent, and the like. It has been found that annealing the bioriented film reduces the tendency of the film to pucker during heat-sealing. Preferably, the resin from which the bioriented film is made should be extruded and the films should be melt-fusible for good sealing.

Since these films will be utilized in connection with viable and/or perishable materials, they must meet the requirements established for such use. For example, it has been found that for films intended for use as the packaging material for blood, blood platelets, other components of blood and the like, the resin formulation should be relatively free of toxic and/ or migratory agents such as plasticizers, anti-oxidants, anti-blocking and slip agents to obviate the possibility of these agents leaching out and contaminating the contents of the package. This criteria would also apply with regard to other typically utilized additives such as stabilizers, lubricants, colorants and the like. However, when the film is intended for use as a packaging material for other materials, such as food stuffs, greater freedom can be exercised regarding the type and quantity of additives and agents which can be incorporated in the resin formulations, provided the incorporation of such additives and/ or agents meets with established approval and will not deleteriously affect the contents of the package. Which additives can be utilized and in what quantity can be readily determined by and fall within the knowledge of the skilled, informed artisan.

Of particular significance is that the biaxially oriented polyolefin films of this invention can be used as packaging material for the preservation of blood, blood platelets, other components of blood and the like at cryogenic temperatures and, more particularly, at liquid nitrogen temperatures (-196 C.). A great deal of research has been and continues to be conducted regarding the characterization of diiferent blood types and the collection, storage, freezing, handling and reconstitution of human blood for future use. According to present methods, blood is collected from the donor in specially constructed, plasticized vinyl chloride bags which are provided with a small diameter vinyl tubing. After collection, small samples of the blood are sealed off in the attached vinyl tubing in order to facilitate sampling of the blood for various purposes. The blood samples are then stored at refrigerated temperatures which are usually above freezing (about 40 F.) until processed and/or subsequently frozen.

The processing of blood for storage consists in separating the blood plasma from the whole blood by centrifugation. The plasma is then freeze-dried and the blood cell portion of the centrifugate is then modified by adding thereto a 15% glycerol solution which serves as a preservative for the blood cells at sub-zero temperatures. This mixture is then placed in special containers and frozen at a predetermined rate by immersing the container in liquid nitrogen. After freezing, the blood is then stored in these containers at liquid nitrogen temperatures for a year or more as required. Presently, specially constructed stainless steel or aluminum containers are generally employed for this purpose.

The frozen blood cells can be reconstituted by thawing them at a prescribed rate through the immersion of the container in appropriate liquids. After thawing, the glycerine is removed by repeatedly rinsing the blood cells with bufler solutions and then subjecting the rinsed and Washed blood cells to centrifugation. After the blood cells have been reconstituted, they are then mixed with solutions of plasma reconstituted from freeze-dried plasma in order to obtain blood suitable for human transfusion.

The use of a material as a substitute for the presently employed stainless steel or aluminum containers for packaging and preserving blood at cryogenic temperatures must, therefore, meet the same criteria as do the stainless steel or aluminum containers. Generally, such a material must exhibit the following properties: it must have good structural strength and flexibility at cryogenic temperatures down to liquid nitrogen temperatures; that is, to at least about 196 C.; it must exhibit low permeability and it must readily lend itself to conventionally and presently employed fabricating techniques. Preferably, the material should also be translucent or transparent. A plastic material, such as the biaxially oriented polyolefin films of this invention, must especially exhibit inertness when in contact with blood; be heat scalable and having heat seals which are durable at low temperatures. Ideally, such a container would be one equipped with side tubes for the collection of blood from a donor, permit centrifugation to remove plasma, be able to be subjected to cryogenic temperatures of at least about -196 C. and storage at these temperatures for prolonged periods of time, withstand subsequent reconstitution of the blood or plasma contained therein and, ultimately, be used as the transfusion container.

The invention will become more clear when considered together with the following examples which are set forth as being exemplary and are not intended in any way to be limitative thereof. Unless otherwise designated, all percentages are by weight.

EXAMPLE I One criterion of the usefulness of plastic films as a packaging material at cryogenic trneperatures to at least about --196 C. is its ability to be flexed at these temperatures without cracking, rupturing or otherwise failing and Without damaging the materials packaged therein. In order to determine the ability of various plastic films to resist damage or failure during flexing at cryogenic temperatures, samples of a variety of plastic films were first coiled into a loose roll, immersed in liquid nitrogen (196 C.) for at least about 30 seconds, and immeediately thereafter removed from the liquid nitrogen and subjected to severe flexing by hand. The results of these tests, as determined by a visual inspection of the films, are set forth in Table I below wherein there is set forth the general manner in which the resins were fabricated into films in the column headed Type of Film, the properties of the resins and the films, and the intrinsic viscosity of [the resins as determined by dissolving them in Decalin at C. In the column headed Type of Film, the term blow ratio refers to the ratio of the fiat width of a tubular, extruded film versus the diameter of the nozzle through which the film was extruded.

TABLE I.-RESISTANCE TO FLEXING OF VARIOUS FILMS AT CRYO GENIC TEMPERATURES (196 C.)

Resin properties Intrinsic Film Properties viscosity Condition of Film (in Decalin Thickness Fihn After No Type of film at 130 0.) Density Melt Index Density (Mils) Cold Flexing 1 Bioriented, irradiated low density polyethylene film, irradi- Insoluble 0.92 2.0-2. 5 Very slight ated before orientation. shattering. 2 Bioriented, low density polyethylene; no additives 1. 3 0. 9172 0. 098 0. 9185 1. 4-2. 3 Undamaged. 3 .do 1. 3 0. 9178 0.078 O. 9190 0. 8-1. Do. 4 Bilglriefited, low density polyethylene containing 0.75% anti- 1.3 0.9178 0.078 0.9231 1. 7-2.3 Do.

00 agen 5 Bioriented, low density polyethylene; no additives 1. 2 0.9189 0. 11s 0. 9229 0.7-9.0 Do. 6 .do 1. 23 0. 9189 0. 193 0. 9233 1.0 Do. 7 Bioriented ethylene copolymerized with rropylene copolymer- 2. 75-2. 79 0. 910 0. 69 0.910 1.0 Do. 8 Bioriented, low density polyethylene; no additives 1. 2 0. 9152 0 27-0. 39 0. 9174 1. 75-2. 0 Do. 9..... do l. 1 0. 920 1. 7-2. 4 0. 9206 1. 75-2. 0 Shattered readily. ..d0 1. 2 0. 9199 0. 25 0. 9233 1. 5 Undamaged.

Bioriented, high density polyethylene 2. 9 0. 960 0 20-0. 30 0.9592 0. 4-0. 5 Do. Biorieilted etliylene-methyl acrylic acid copolymer cont Insoluble 0. 940 1. 2 0. 9450 0. 75 Do.

a. so um sa 1;. 13 Bloriented ethylene-acrylic acid copolymer iii-6% acrylic acid.- Insoluble 2. 4 0. 75-0. 90 Do. 14 Bioriented polypropylene 6 0.89 1.0 0. 905 1. 0 D0. 15 Blown, low density polyethylene; blow ratio 7 :1 1. 3 0.9175 0. 09 0.9196 2.0 shattgrled rea 1 y 16"... Blown, low density polyethylene; blow ratio 6.8: 1 1. 3 0. 9193 0. 05-0. 06 0. 9197 1. 0 Do. 17 do 1. 23 0. 9189 0. 19 0. 9185 1. 0 Do. 18 Blolwn. ethylzerie vinyl acetate; 18% vinyl acetate copolymer; 1 02-1. 03 O. 94 5. 0 0.9539 0.9-1. Do.

b ow ra io 19 Bioriented, ethylene-vinyl acetate copolymer, 28% vinyl ace- 1. 46-1. 48 0. 9499 0.21 0. 9555 1. 2-1. 5 Undarnaged.

tate copolymer. .d0. 1. 04-1. 08 0. 9490 1. 20 0. 9539 0. 7-1. 0 Shattered readily.

1 Does not fully melt.

From the results set forth in Table I above, it can be seen that, in general, the biaxially oriented polyolefin films (Films Nos. 2-8 and 10-14) appear tobe quite resistant to flex damage at liquid nitrogen temperatures. It will also be noted that the biaxially oriented polyolefin and polyolefin copolymer films obtained from resins having an intrinsic viscosity greater than 1.2 were more resistant to flex damage than films obtained from those resins having lower intrinsic viscosity (Film No. 9). All of the blown polyolefin films (Films Nos. 15-18) can be seen to be severely damaged when flexed at liquid nitrogen temperatures. The bioriented ethylene vinyl acetate copolymer films obtained from resin formulations having a low intrinsic viscosity (Films Nos. 18-20) were severely damaged opon flexing.

EXAMPLE II A commonly accepted standard of determining the effectiveness of freezing and storing blood cells and then reconstituting the blood for subsequent use is the minimum levels of hemoglobin in the supernatant of the centrifuged blood after it has been thawed and washed since most of the damage to blood cells is believed to occur during freezing. According to generally accepted standards, the percent recovery of the hemoglobin should be at least 50% to attain an effective freezing, storing and reconstitution use. By use of packages fabricated from the polyolefin biaxially oriented plastic films of the invention, it was found that recovery levels of supernatant hemoglobin were in the range of from about 89.5% to 94.3% which recovery compares very favorably with those obtained heretofore when stainless steel containers were used for packaging and storing blood cells at liquid nitrogen temperatures.

This result was obtained by utilizing the biaxially oriented polyethylene films from Films Nos. 2, 3, 5, and 6 in Table I above to fabricate packages in which blood samples were tested from the time they were taken from a donor through storage at liquid nitrogen temperatures and subsequent reconstitution. After being taken from a donor, the blood cells were centrifuged free from the blood plasma and approximately 14% glycerol was added to the blood cells. The blood cells containing glycerol were then placed in the polyethylene biaxially oriented film bags identified hereinabove which measured approximately 10" square and which were heat sealed closed after the blood had been placed therein. The biaxially oriented polyethylene bags were then supported on a metal mesh screen and placed about 1 centimeter apart. The screen supporting the bags was then immersed into liquid nitrogen. The blood cells in the bags were frozen in about 2 minutes and, while they were being frozen, they were not agitated; that is, they were not shaken or disturbed. Thawing of the blood samples was carried out in water which was maintained at a temperature of about 45 C. with mild agitation of the bags in the water until the temperature of the blood samples in the bags was about 15 -20 C. Agitation of the bags containing the blood samples was achieved by slowly moving the bags manually through the water bath. Complete thawing of the blood samples was attained in about 2% minutes which was comparable to that usually required when stainless steel containers are employed.

The supernatant hemoglobin level immediately after thawing of the blood cells, was found to be 690 milligrams per 100 milliliters (mg/100 ml.) in the stainless steel containers as opposed to 760 mg./100 ml. in the biaxially oriented polyethylene film bags. After repeated washings to remove the glycerol, the level of the supernatant hemoglobin in the stainless steel containers was measured at mg./10O ml. while in the biaxially oriented polyethylene film bags, it measured 145 mg./ ml. The blood cells were then reconstituted by resuspension in blood plasma at which time the level of supernatant hemoglobin in the stainless steel containers was measured at 30 mg./100 ml. and at 85 mg./100 ml. in the biaxially oriented polyethylene film bags. From this data, the percent overall recovery of the blood cells obtained from the stainless steel containers was calculated to be about 94% :3% while that from the biaxially oriented polyethylene film bags was calculated to be about 93.4%.

It can be seen, therefore, that blood frozen in the plastic, biaxially oriented film packages of the invention compared at least as favorably with blood frozen in stainless steel containers and that these biaxially oriented films can be utilized to package and maintain blood at liquid nitrogen temperatures for indefinite periods and then be used to reconstitute the blood for subsequent use.

Although the present invention has been described in some detail with regard tothe packaging, freeze-storing and reconstitution of blood, blood platelets, blood cells, and other components of blood, it should be understood that these biaxially oriented polyolefin films can be utilized with equal effectiveness and in substantially the same manner as has been disclosed and described herein for packaging and freeze-storing fresh fruits, vegetables, fresh meats and the like. Additionally, these biaxially oriented polyolefin films also lend themselves to the storage of cultures which are used primarily as bulk starters in the manufacture of cheeses and for the fermentation of such food items as olives, cucumbers, sauerkraut, beer and the like; to preserve human and animal organs and tissues such as bone, cornea, skin and the like as well as human kidneys for subsequent transplant; to store both animal and human semen which can be subsequently used for artificial insemination; to store and ship pathogens for future study and examination; and to store, ship and preserve miscellaneous animal cultures such as tumors for subsequent study and evaluation.

Hence, while the present invention has been described in some detail and with particularity it should be understood that changes, modifications and alterations can be made therein with departing from the scope and spirit of the invention.

What is claimed is:

1. A process for storing and preserving viable and perishable materials at cryogenic temperatures on the order of about that of liquid nitrogen, which process comprises providing a polyolefin film which has been biaxially oriented to at least 300% in both the machine direction and the transverse direction at a temperature between about 15 F. and 50 F. below its melting point, said polyolefin film having been obtained from a polymer composition consisting of at least 50% by weight of a polyolefin selected from the group consisting of polyethylene and polypropylene, the remainder of said composition being selected from the group consisting of acrylic acid, methacrylic acid, vinyl acetate, ethyl acrylate, butylene and neohexene, said polymer composition having an intrinsic viscosity in Decalin at 130 C. of at least 1.2,

contacting said viable and perishable materials with said polyolefin film and packaging them in said film, and

storing said materials packaged in said film at a temperature about that of liquid nitrogen.

2. The process of claim 1, wherein the polyolefin film has been obtained from a composition which is substantially all polyethylene.

3. The process of claim 2, wherein the substantially all polyethylene composition has a density of up to 0.925.

4. The process of claim 1, wherein the polyolefin film has been obtained from a composition which is substantially all polypropylene.

5. A package comprising viable and perishable materials for storage at a temperature about that of liquid nitrogen contained within a polyolefin film which has been biaxially oriented to at least 300% in both the machine direction and the transverse direction at a temperature between 15 F. and F. below its melting point, said polyolefin film having been obtained from a polymer composition consisting of at least 50% by weight of a polyolefin selected from the group consisting of polyethylene and polypropylene, the remainder of said composition being selected from the group consisting of acrylic acid, methacrylic acid, vinyl acetate, ethyl acrylate, butylene and neohexene, said polymer composition having an intrinsic viscosity in Decalin at C. of at least 1.2.

References Cited UNITED STATES PATENTS 2,838,046 6/1958 Butler 128-272 3,177,117 4/ 1965 Saunders 424-101X 3,217,073 11/ 1965 Olson et al. 264-289X 3,257,072 6/1966 Reynolds 206-47X 3,284,551 11/1966- Yumoto et a1 264-289X 3,299,194 1/ 19 67 Golike 161-402X FRANK W. LUTTER, Primary Examiner W. L. MENTLIK, Assistant Examiner US. 01. X.R.

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