WO1998001752A1

WO1998001752A1 - Device for minimizing outgassing from fluid

Info

Publication number: WO1998001752A1
Application number: PCT/US1997/011863
Authority: WO
Inventors: Victor E. Kimball; Irvin T. Pierskalla; Edward J. Anderson
Original assignee: Optical Sensors Incorporated
Priority date: 1996-07-08
Filing date: 1997-07-07
Publication date: 1998-01-15
Also published as: AU3597297A

Abstract

A device (10) is provided for minimizing outgassing of a gas dissolved in a fluid at a predetermined partial pressure. The device includes a first pouch (12) containing the fluid (18) and a compressing means (14, 42, 42', 52, 52') for subjecting the first pouch to greater-than-ambient pressure. Methods are also provided for using the device to minimize outgassing.

Description

DEVICE FOR MINIMIZING OUTGASSING FROM FLUID

Technical Field

This invention relates generally to fluid packaging. More particularly, the invention relates to devices for packaging fluids containing dissolved gases and to methods of using such devices to minimize outgassing of such fluids.

Background Art

Flexible packages are commonly used to contain fluids for convenient and inexpensive storing, transporting and dispensing. For example, flexible packages containing foods, juices, soft drinks and dairy products are available in the retail marketplace. Sterile solutions such as normal saline, dextrose, and the like can also be contained in flexible packages. Similarly, reference fluids that can be used to calibrate and perform quality control measurements on blood gas analysis and other types of medical equipment are often provided in a flexible package.

Typically, a flexible package is fabricated from a polymeric material. Such a material is easily manufactured and fabricated in the form of a package which is readily sterilized. In addition, the package may be made of a metal-plastic laminate. A laminated package made from layers of a low gas-permeability polymer and a metal foil provides the additional benefit of being substantially gas-impermeable.

The use of a pouch-like container in a method of preparing sterilized, packaged articles is described in U.S. Patent No. 3,892,058 to Komatsu et al. The container described in Komatsu et al. is a laminate of flexible sheet materials. The inner layer is composed of a heat-sealable resin, such as a polyamide. The outer layer is composed of a heat-resistant resin, such as a polyester film. Sandwiched between the inner and outer layers is a metal foil, such as aluminum.

U.S. Patent No. 4,116,336 to Sorensen et al. describes the use of a flexible, gas-tight package to contain a fluid containing dissolved O₂ and/or CO₂. The fluid may be used for calibrating or quality control monitoring of blood gas measuring equipment. The flexible container is a plastic-laminated metal foil, e.g., aluminum. The exterior surface of the metal foil is laminated with a plastic foil, such as a polyester film, to prevent scratching, and the like. The inner surface of the metal foil is laminated with a plastic having low gas permeability and good weldability, such as poly vinylidene chloride or polyethylene terephthalate.

Reference fluids useful for calibrating and performing quality control measurements on blood gas analysis or other medical equipment provide a standard against which the equipment is calibrated with respect to, for example, hydrogen ion concentration (pH) and dissolved oxygen and carbon dioxide partial pressure (pO₂ and pCO₂, respectively). In order to obtain reliable data from the equipment, it is important that the pH, pO₂ and pCO₂ values of the reference fluid, once the fluid has been prepared, calibrated, and packaged, be maintained within a specific and very narrow range during shipping and storage. In addition, since many of the reference fluids are used in in vivo or in situ applications, such as with an indwelling arterial catheter, as described in U.S. Patent No. 4,830,013 to Maxwell, or a paracorporeal system for bedside blood chemistry analysis as described in commonly owned, co-pending U.S. Application Serial No. 08/379,332 to Kimball et al., filed January 27, 1995, entitled "In Situ Calibration System for Sensors Located in a Physiologic Line," they must be biocompatible and prepared under sterile conditions, and the sterility of the fluids must be maintained during shipping and storage. Reference fluids are currently packaged in devices which insure that the gas concentrations will be maintained for the storage lifetime of the package. Such devices include an inner package containing the reference fluid, for example, as described in U.S. Patent No. 4,1 16,336 to Sorensen et al. The inner package is sealed in an outer pouch that serves as a sterility barrier. The outer pouch may be, for example, a Tyvek®-backed polymeric material. In addition, the packaging material may be used as a storage medium for shipping the reference fluid.

The solubility of a gas in a fluid is dependent on not only the nature of the fluid and of the gas but also on the temperature and pressure of the fluid. It is well known in the art that the effects of temperature and pressure on gas solubility are interrelated. At any given temperature, the solubility of a gas in a fluid increases with increasing pressure. Similarly, at any given pressure, the solubility of most gases in a fluid decreases with increasing temperature.

Gases may be dissolved in the fluid by bubbling with known concentrations of, for example, O₂ and CO₂, to provide a liquid with known pO₂ and pCO₂. Fluids thus prepared are placed and sealed in a flexible package for shipping and storage. Exposing the filled and sealed pouch to an elevated temperature, reduced pressure, or both, may result in outgassing. For example, if the filled and sealed pouch is exposed to low pressure during shipment and/or storage, outgassing may occur.

In addition, fluids containing dissolved gases may be prepared at pressures lower than and/or temperatures greater than ambient pressure to reduce the potential for outgassing. However, subsequent exposure of the package to conditions in which the pressure is less than that used during manufacture or to temperatures that are higher than those used during manufacture, may result in outgassing. Outgassing results in a diminution of the partial pressure of the gas in the fluid, thereby compromising the utility of the fluid as a reference fluid. Such effects are most often seen during shipment of the packages under uncontrolled conditions, shipment to sites at high altitudes (i.e., low pressure), or shipment or storage at elevated temperature.

One method of resolving this problem is to prepare the reference fluid at a pressure below ambient, as described in U.S. Patent No. 4,1 16,336 to Sorensen et al. This requires equilibrating the fluid with the gas at subatmospheric conditions, which would reduce outgassing under low pressure conditions. Another method would be to prepare the fluid at an elevated temperature, which would reduce outgassing at elevated temperatures. Preparing fluids at subatmospheric and elevated temperatures conditions would provide the combined effect of reducing outgassing under low pressure conditions, elevated temperatures, or both. Yet another method of minimizing outgassing would be to ship and/or store the fluid at a pressure above which the fluid-filled package was manufactured, at a temperature below which the package was manufactured, or both. However, this would result in a dramatic increase in shipping and storing expenses.

Accordingly, there remains a need in the art for a flexible packaging device suitable for containing fluids having gases dissolved therein and minimizes outgassing, thereby allowing the efficient shipping and storing of such fluids. The present invention provides such a device, and involves pressurizing the fluid- filled pouch to minimize outgassing. In addition, a method is provided for minimizing outgassing of a gas dissolved in a fluid.

Disclosure of the Invention

Accordingly, it is a primary object of the invention to address the above-mentioned needs in the art by providing a novel device for containing a fluid having a gas dissolved therein, which has improved shipping and storage properties.

It is another object of the invention to provide a device for minimizing outgassing of a gas dissolved in a fluid at a predetermined partial pressure.

It is yet another object to provide a method for using the aforementioned device. Additional objects, advantages and novel features of the invention will be set forth in part in the description which follows, and in part will become apparent to those skilled in the art upon examination of the following, or may be learned by practice of the invention. In one aspect of the invention, a device is provided for minimizing outgassing of a gas dissolved in a fluid. The device includes a sealed, gas-impermeable pouch comprised of a laminate of a metal and a plastic, containing the fluid and the gas dissolved therein. Outgassing during shipping, storage, and/or handling is minimized by providing a compressing means affixed to the pouch. In one embodiment, the compressing means is clamping means or an elastomeric band secured to the pouch. In another embodiment, the compressing means is a second pouch that encases the first pouch so as to provide a space between the two pouches that can be pressurized with an atmosphere at greater-than- ambient pressure. In yet another embodiment, the second pouch is itself secured by a pressurizing means to maintain the atmosphere between the pouches at a greater-than- ambient pressure.

In another aspect of the invention, a method is provided for minimizing outgassing of a gas dissolved in a fluid at a predetermined partial pressure. In one embodiment, the method comprises providing a sealable, gas-impermeable first pouch containing the fluid and the gas dissolved therein, sealing the first pouch so as to form a gas-tight, sealed pouch that is void of any gas phase, and affixing a compressing means for maintaining the first pouch at a pressure greater than ambient. While these devices and methods can be used for a variety of purposes, depending on the components of the fluid contained in the first pouch, they will primarily be used in shipping and storing reference fluids having a predetermined pH, pO₂, and/or pCO₂ suitable for use in calibrating or performing quality control measurements on blood gas analysis equipment.

Brief Description of the Drawings

In the course of this description, reference will be made to the attached drawings, wherein: FIG. 1 is a cross-sectional view of a first fluid-filled pouch encased within a second pouch according to the present invention.

FIGS. 2 A, 2B, 2C, and 2D represent cross-sectional views of a fluid-filled pouch and embodiments of compressing and pressurizing means according to the present invention.

Modes for Carrying Out the Invention Definitions:

Before the present devices and methods are disclosed and described, it is to be understood that this invention is not limited to a specific flexible package material, a specific fluid, or particular dissolved gases, as such may, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting.

It must be noted that, as used in the specification and the appended claims, the singular forms "a," "an" and "the" include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to "a gas" includes two or more gases, reference to "an elastomeric band" includes two or more such bands, and the like.

In describing and claiming the present invention, the following terminology will be used in accordance with the definitions set out below.

The term "partial pressure" is used in its conventional sense to refer to the pressure exerted by one component of a mixture of gases, or by a gas dissolved in a fluid, if the component or the gas were present alone in a container. The partial pressure of a gas is generally abbreviated as, for example, "pO₂" for oxygen, "pCO₂" for carbon dioxide, and so forth.

The term "ambient" is used herein to mean standard atmospheric conditions. Thus, the term "ambient pressure" is intended to mean approximately 740 mm Hg to about 780 mm Hg. The term "ambient partial pressure" of a gas is intended to mean the partial pressure of a component of the atmosphere in ambient conditions. Thus, the ambient partial pressure of O₂ is approximately 150 mm Hg to 155 mm Hg. A pressure that is "greater than ambient" is one that varies from ambient pressure by at least 5%, i.e., 798 mm Hg, preferably by at least 50%, i.e., 1140 mm Hg, more preferably by at least 100%, i.e., 1520 mm Hg.

The term "outgassing" is used herein to mean the release of a dissolved gas by heating, depressurization, agitation, or the like. The term "outgassing" broadly includes bubble formation or gases otherwise coming out of solution when the temperature of the fluid is increased, when the pressure of the fluid is reduced, such as at high altitudes, when the fluid is agitated during shipping, or when any combination of increased temperature, decreased pressure and agitation occurs.

The terms "compressing means" and "pressurizing means" are used herein to refer to a means for producing a force on a flexible package so that the contents thereof are maintained at a greater-than-ambient pressure, preferably at a pressure effective to prevent outgassing. Suitable materials for "compressing means" and "pressurizing means" will be outlined below.

The term "charge" or "charging" as used herein is intended to mean the introduction of an atmosphere or a gas into a space designed to contain the atmosphere or gas. "Charging" a space with an atmosphere or a gas includes but is not limited to introducing an atmosphere or a gas into such a space at ambient or nonambient pressure.

"Optional" or "optionally" means that the subsequently described circumstance may or may not occur, and that the description includes instances in which said circumstance occurs and instances in which it does not. For example, the phrase "optionally including an additional plastic layer" means that an additional plastic layer may or may not be present, and the description includes both the instance when the additional plastic layer is present and the instance when the additional plastic layer is not present. The invention, together with additional features and advantages thereof, may best be understood by reference to the following description taken in connection with the illustrative drawings, wherein like reference numbers designate corresponding parts throughout the several embodiments. With reference to FIG. 1 , a device for minimizing outgassing of a gas dissolved in a fluid at a predetermined partial pressure is shown generally at 10. The device comprises an inner pouch 12 and an outer pouch 14 which encases the inner pouch and provides a space 16 between the inner pouch 12 and the outer pouch 14. Inner pouch 12 is gas-tight and contains a fluid 18 in which a gas has been dissolved. Inner pouch 12 can be of any size and the volume of the fluid 18 contained in the pouch any volume, but typically the size of the pouch is sufficient to contain about 0.5 to about 500 mLs or more. Inner pouch 12 is filled with fluid 18 so that there is no gas phase enclosed within the pouch.

Inner pouch 12 may be fabricated from any flexible gas-tight material or from a laminate of materials. Such a laminate is described in U.S. Patent No. 4,116,336 to Sorensen et al. In one embodiment, inner pouch 12 is composed of layers 20, 22, and 24 that are laminated together and sealed by, for example, welding the interior layer 20 to form welding seam 26 at edge 28. Preferably, the opposite edge of the bag 30 is also welded along a welding seam 32.

The interior layer 20 of the laminate is preferably a low-permeability plastic, examples of which are well known in the art, and has a thickness of about 25 μm to about 75 μm. Layer 22 is preferably a metal foil, such as aluminum. Optionally, an additional plastic layer may be present between layers 20 and 22 to provide a binder layer. Optional exterior layer 24 is provided as a protective layer over layer 22.

Before inner pouch 12 is sealed, it is filled with a fluid in which gases are dissolved. One preferred such fluid is a biocompatible reference fluid for use in calibrating or performing quality control measurement on blood gas analysis equipment. The reference fluid may be a medium which contains known analyte concentrations. Such analytes include gases, for example, O₂, CO₂ or the like, hydrogen ion, i.e., pH, or other biological analytes the presence of which may be desirable to assess in a physiologic fluid, e.g., glucose, potassium, calcium, and the like. In addition, the reference fluid may contain biocompatible buffers including, for example, bicarbonate, phosphate and fluorocarbon- based synthetic buffers. The composition of and methods for preparing reference fluids are well known in the art. Such compositions are described in, for example, U.S. Patent Nos. 3,380,929 to Petersen, 3,681,255 to Wilfore et al. and U.S. Patent No. 4,116,336 to Sorensen et al. Outer pouch 14 is preferably constructed of a laminate of layers 20', 22', and 24' using materials similar to those used in layers 20, 22, and 24 in inner bag 12, and sealed by welding interior layer 20' to form welding seam 26' at edge 28' and a welding seam 32' at opposite edge 30'. However, any flexible, gas-tight package can be used for the outer pouch. Outer pouch 14 is larger than inner pouch 12 so as to encase the inner pouch and to provide a space 16 therebetween. Prior to sealing the outer pouch, space 16 can be charged with an atmosphere having a predetermined composition and/or an atmosphere at a pressure greater than ambient. Thus, for example, the partial pressure of the gas in the atmosphere may be substantially the same as, or slightly biased with respect to the partial pressure of the dissolved gas. In order to minimize outgassing according to the embodiment of the invention shown in FIG. 1, inner pouch 12 is pressurized by charging space 16 with an atmosphere at a pressure effective to prevent outgassing. Preferably, but not necessarily, the atmosphere is one containing the gas dissolved in the fluid in the inner pouch and in which the partial pressure of the gas is substantially the same as the partial pressure of the dissolved gas. Alternate embodiments of a device for minimizing outgassing of a gas dissolved in a fluid at a predetermined partial pressure may be best understood by reference to the FIGS. 2A, 2B, 2C, and 2D.

FIG. 2A illustrates one preferred embodiment of such a device generally at 40. Flexible pouch 12 containing fluid 18 in which a gas is dissolved, may be pressurized. Compressing means 42 is affixed to flexible pouch 12, and is designed to provide a pressure on the pouch effective to minimize outgassing. One of skill in the art will recognize that the amount of pressure that is required to minimize outgassing of a fluid will depend on a number of variables including the nature of the fluid, the nature of the gas, the fluid manufacturing process, and the like. As illustrated in FIG. 2A, compressing means 42 is a clamping means. For shipping andVor storing flexible pouch 12, the clamping means preferably comprises the material in which the pouch is packed. Thus, as shown in FIG. 2A, flexible pouch 12 may be placed in a paperboard or plastic shipping/storing sleeve 42 that provides a pressure on the gas sufficient to minimize outgassing. The clamping means may also be a spring clip, manufactured by conventional means from any of a variety of metals or plastics, that is biased toward closing. Alternatively, as illustrated in cross-section FIG. 2B, device 50 includes as a compressing means an elastomeric band 52 secured about the flexible pouch 12.

FIGS. 2C and 2D illustrate additional embodiments of the invention at 60 and 70, respectively, in which first pouch 12 is encased in second pouch 14, and space 16 formed therebetween is charged with an atmosphere. As illustrated in FIG. 2C, device 60 includes pressurizing means 42'. In this embodiment, pressurizing means 42' is a clamping means as described with respect to FIG. 2A. Again, a preferred clamping means for shipping or storing flexible pouch 12 encased in second pouch 14 comprises the materials in which the second pouch is packaged. As illustrated in FIG. 2D, device 70 includes pressurizing means 52'. In this embodiment, pressurizing means 52' is an elastomeric band as described with respect to FIG. 2B.

The disclosed device and method for minimizing outgassing of a gas dissolved in a fluid at a predetermined partial pressure are designed to be used with reference fluids for calibrating and performing quality control measurements of blood gas (O₂ and CO₂) and pH sensors situated in an arterial line in a human or animal subject, as described in Kimball et al., supra. However, utility can be extended to any type of reference fluid or other fluid in which gases may be dissolved at a predetermined partial pressures that must be maintained within critical tolerance ranges.

Claims

We claim:

1. A device for minimizing outgassing of a gas dissolved in a fluid at a predetermined partial pressure, comprising a sealed, gas-impermeable first pouch comprised of a laminate of a metal and a plastic, containing the fluid and the gas dissolved therein, and a compressing means for maintaining the first pouch at a pressure effective to minimize outgassing.

2. The device of claim 1 , wherein the pressure is greater than the ambient pressure.

3. The device of claim 2, wherein the compressing means comprises a second pouch adapted to encase the first pouch, thereby providing a space therebetween which is charged with an atmosphere at the greater-than-ambient pressure.

4. The device of claim 2, wherein the compressing means comprises a second pouch adapted to encase the first pouch, thereby providing a space therebetween which is charged with an atmosphere, and a pressurizing means for maintaining the atmosphere in the space at a pressure greater than ambient.

5. The device of claim 1 , wherein the compressing means is a clamping means or an elastomeric band.

6. The device of claim 4, wherein the pressurizing means is a clamping means or an elastomeric band.

7. The device of claim 1, wherein the fluid is a reference fluid for calibration, quality control measurements, or both calibration and quality control measurements of a blood gas analysis apparatus.

8. The device of claim 3, wherein the second pouch comprises a laminate of a metal and a plastic.

9. The device of claim 4, wherein the second pouch comprises a laminate of a metal and a plastic.

10. A method for minimizing outgassing of a gas dissolved in a fluid at a predetermined partial pressure, comprising (i) providing a sealable, gas-impermeable first pouch comprised of a laminate of a metal and a plastic, containing the fluid and the gas dissolved therein, (ii) sealing the first pouch so as to form a gas-tight, sealed first pouch which is void of any gas phase therein, and (iii) affixing to the first pouch a compressing means for maintaining the first pouch at a pressure effective to minimize outgassing.

11. The method of claim 10, wherein the pressure is greater than the ambient pressure.

12. The method of claim 11 , wherein the compressing means comprises a sealable second pouch adapted to encase the first pouch, and step (iii) comprises encasing the sealed first pouch in the second pouch so as to provide a space therebetween, charging the space at the greater-than-ambient pressure with an atmosphere in which the gas is present, and sealing the second pouch to form a gas-tight, sealed second pouch and a sealed space.

13. The method of claim 11, wherein the compressing means comprises a second sealable pouch adapted to encase the first pouch, thereby providing a space therebetween which is charged with an atmosphere, and a pressurizing means for maintaining the atmosphere in the space at a pressure greater than ambient.

14. The method of claim 10, wherein the compressing means is a clamping means or an elastomeric band.

15. The method of claim 13, wherein the pressurizing means is a clamping means or an elastomeric band.

16. The method of claim 10, wherein the fluid is a reference fluid for calibration, quality control measurements, or both calibration and quality control measurements of a blood gas analysis apparatus.

17. The device of claim 12, wherein the second pouch comprises a laminate of a metal and a plastic.

18. The device of claim 13, wherein the second pouch comprises a laminate of a metal and a plastic.