DE2716178A1 - METHOD OF MANUFACTURING A GAS IMPERMEABLE PACKAGE AND THE PACKAGE MANUFACTURED THEREOF - Google Patents

Description

Patent attorneys Dipl.-Ing. H.Weickmann, Dipl.-Phys. Dr. K. Fincke

Dipl.-Ing. F. A. Weickmann, Dipl.-Chem, B.JHij.ber

8 MUNICH 86, DEN

PO Box 860820

MÖHLSTRASSE 22, CALL NUMBER 98 3921/22

17,969-F - H / WE / rm

CORDIS DOW CORPORATION
Miami, Florida, USA

Process for the production of a gas-impermeable packing and the packing produced thereby

The invention relates to the packaging of articles of the "dry type", in particular from artificial kidney dialyzers using hollow fiber membranes to a controlled one Package containing atmosphere or environment.

Articles, such as artificial kidney dialyzers of the dry type, which use permeable hollow fiber membranes

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are typically sterilized with ethylene oxide. After the sterilization, the ethylene oxide gas in the dialyzer becomes completely during a degassing time replaced by aseptic air. Before dialysis, the dialyzer must be cleared of air and sucked in or out. To be brought up and running. In such a procedure, the air is flushed out of the dialyzer and blood lines redirect a saline solution through the dialyzer. Typically, a dialyzer that is started requires a strong, firm tapping of the dialyzer itself, the drip chambers and the blood lines, causing small air bubbles effectively removed therefrom. Often requires the amount of saline solution used and the maintenance required for the start-up of a dialyzer for a long time and specialist staff and thereby the need for dialysis for everyone Patient time required significantly increased. It is also believed that the strong knocking that leads to the Removal of air bubbles from the dialyzer is required, often damaging the membranes and leaking in generated in the dialyzer, making the dialyzer impossible to use.

In another procedure, when starting up or sucking in a dry, air-filled dialyzer, the arterial blood line, which is connected to the dialyzer, connected to a COp cylinder and the dialyzer is flushed with COp for 4 to 5 minutes to remove the air from the dialyzer and the blood lines. The dialyzer is then started in a manner similar to that described above or the suction takes place in a similar manner Way as described above. When one speaks of set in motion, this expression should also include suction. _ ^ _

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Although it has been found that a dialyzer which is purged with COo first is generally easier to start up or that priming can be done more easily and in less time compared to an air-filled dialyzer, is that described above COg flushing method disadvantageous for other reasons. Even if the start-up time can be shortened with a saline rinsing solution, additional time is required for the individual or medical technical assistant _{to connect the dialyzer to CO 2} and to rinse it. This also increases the cost. Extra space must also be provided for the COg cylinders and a corresponding supply of CO ₂ must be kept. Furthermore, this start-up resp /. Suction process increases the risk of contamination of the dialyzer, since extra lines are required for a complete start-up of the dialyzer. The effect of these factors is that all the advantages that are obtained from an easier start-up and, if necessary, from the required time, are canceled out again.

The invention relates to a method for producing a gas-impermeable packing, α.e an object and Contains a controlled atmosphere characterized by the following stages: (a) Establishing a Packing by sealing the object in an envelope or housing (these terms become used synonymously), which is impermeable to gas,

(b) creation of a gas-permeable zone in the envelope,

(c) sterilizing the package, (d) evacuating the package, (e) introducing a controlled gas atmosphere into the Packing and (f) sealingly dividing the packing into a first section containing the gas-permeable zone and a

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second section that contains the item, creating a gas-impermeable package that controls the item and one Contains gas atmosphere is generated.

The invention also relates to a method of manufacturing an article and a controlled atmosphere containing gas-impermeable packing, which is characterized by the following stages: (a) sealing or tightly packing the object in a first envelope which is permeable to gas, (b) sterilizing the tightly packed object, (c) wrapping the tightly packed object with a second gas-impermeable Wrapping with the formation of an outer wrapping housing around the sealed or hermetically sealed object, (d) evacuating the sealed object and the outer enclosure, (e) initiating a controlled Atmosphere in the outer envelope and in the sealed article; and (f) sealing the outer envelope to form a gas impermeable package containing the article and a controlled atmosphere.

The invention further relates to a method for producing a gas-impermeable dialyzer, a kidney dialyzer and A controlled atmosphere pack characterized by the following stages: (a) Deployment of a sterilized dialyzer with flow channel closures or inlet opening and outlet opening closures from a permeable material with the formation of a gas-permeable zone in an open, sealable gas-impermeable Housing or an open, sealable, gas-impermeable envelope, (b) evacuating the dialyzer and the enclosure, (c) introducing a controlled atmosphere

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into the envelope and the dialyzer; and (d) sealing the envelope to form a dialyzer and a controlled one Gas-impermeable packing containing atmosphere.

The present invention is explained in more detail with reference to the accompanying drawings.

Fig. 1 is a plan view of a sealed gas impermeable dialyzer pack, shown in phantom the dialyzer contained therein is indicated;

Fig. 2 is a plan view of a sealed gas impermeable package and in dashed lines is that therein included dialyzer indicated;

Fig. 3 is a flow sheet used to explain the process steps for the production of a single pack for the dialyzer, which is shown in Figure 1, dierrt;

Fig. 4 is a flow sheet showing the process steps for Manufacture of a double pack for the dialyzer explained.

According to the invention, a dialyzer is provided which is packaged in a gas-impermeable material is. The pack and the dialyzer are filled with a controlled atmosphere or environment that is compatible with it enables the dialyzer to be put into operation without the need for pre-winding procedures, whereby the start-up or suction of the dialyzer is significantly improved. Packaged dialyzers that

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of a first gas-permeable envelope or gas-impermeable Sheath, which contains a zone with gas permeability, are enveloped, which in turn by a second gas-impermeable Outer pack is wrapped, are also the subject of the present invention. Process for the production of such Packaged dialyzers are also a subject of the present invention.

In the embodiment shown in Figure 1, a packaged and sealed dialyzer 1 is present, the a hollow fiber end dialyzer 2 having dialysate inlet and outlet ports 3 and 4 and blood inlet and outlet ports 5 and 6 and which is surrounded by a gas-impermeable envelope 7. The pack, i.e. the wrapping, and the dialyzer, is sealed and contains a controlled atmosphere in it. This particular pack is also referred to as a "single pack" for a dialyzer or as a simple dialyzer pack.

According to a second embodiment shown in FIG. 2, a sealed packaged dialyzer 8 is used for Provided, the jointly an outer envelope 9 made of a gas-impermeable material and an inner sealed Enclosure 7, in which the dialyzer 2 is located, includes. The inner casing is permeable to gas or, as shown, is made of a gas impermeable material and contains a gas permeable Zone 10. The pack, i.e. the outer and inner covers and the dialyzer, contain a controlled atmosphere. Such a pack is also referred to as a “double pack for dialyzers or as a double dialyzer pack.

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A method for producing a packaged dialyzer is explained in the flow diagram of FIG. According to this flow diagram, the gas-impermeable pack shown in FIG. 1, which contains a dialyzer and a controlled atmosphere, is produced according to the following steps: (a) a pack 11 is produced by sealing a dialyzer 2 in an envelope 7 which is impermeable to gas, manufactured. The envelope is provided with a gas-permeable zone 10, (b) the pack 11 is sterilized; (c) The atmosphere is evacuated from the pack 11; (d) A controlled atmosphere is passed into the pack 11 and (e) the pack is sealed along the line 12-12 into a first part 13 which contains a gas permeable zone 10 and a second part which contains the dialyzer, whereby a gas-impermeable package 1 is formed which contains the dialyzer 2 and a controlled atmosphere.

In another (not shown) embodiment, a packaged dialyzer is made according to the following stages manufactured: (a) A sterilisable dialyzer with inlet and outlet openings made with a permeable material to form gas-permeable zones are covered, is placed in an open gas-impermeable envelope 7, (b) Die Atmosphere is evacuated from the dialyzer and the enclosure, (c) A controlled atmosphere is drawn into the dialyzer and directing the enclosure; and (d) sealing the enclosure, thereby forming a gas-impermeable package which contains the dialyzer and a controlled atmosphere.

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In a further embodiment, as in the scheme As illustrated in Figure 4, a packaged dialyzer is made by the following steps: (a) the dialyzer 2 is sealed in a first envelope 7 which is permeable to gas, (b) the dialyzer and the envelope are sterilized, (c) the sealed dialyzer 11 is sealed by a second gas-impermeable Enclosure 14 is enclosed to form an outer enclosure housing around the sealed dialyzer. (d) The atmosphere is evacuated from the permeable envelope, the dialyzer and from the outer envelope, (e) a controlled one Atmosphere is in the outer casing and in the sealed dialyzer located in a housing initiated, (f) The outer envelope 14 is sealed to form a gas-impermeable packing 15, which the Dialyzer and a controlled atmosphere contains.

In a further embodiment, not shown For example, a prepackaged dialyzer is manufactured through the following steps: (a) A previously sterilized prepackaged dialyzer Dialyzer, in which the cover is permeable to gas, is in a second sealable outer cover, the is gas-impermeable, (b) The atmosphere is made up of the permeable outer covering, the dialyzer and the outer covering evacuated, (c) A controlled atmosphere is drawn into the outer envelope and into the permeable envelope initiated, (d) the outer covering is formed to form a gas-impermeable packing, which the dialyzer and contains a controlled atmosphere, sealed.

The dialyzers that can be packaged in accordance with the present invention can be any dry type units.

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Multiple units can of course optionally be present in a single pack. The invention is particularly suitable for packaging dialyzers that use permeable hollow fiber membranes. at In a preferred embodiment, the packaged dialyzers according to the invention are those in which hollow fiber membranes are used be used. In a further embodiment, the packaged dialyzers are used in blood dialysis is used in which hollow fiber membranes are used.

The term “dialyzer ¹¹ , as used in the present application, means those devices which are suitable for the dialysis of fluids, in particular body fluids such as blood. The term“ pack ”relates to the fully packaged dialyzer and the controlled atmosphere or environment contained in the single or double envelope and the dialyzer.

As used, the term "controlled atmosphere" or "environment" is a generic term and intended to include various gaseous substances that enter the dialyzer to create an aseptic atmosphere are initiated and the suction process or start-up process for dialyzers, in particular for artificial kidney dialyzers, are suitable. The controlled atmosphere contained in the dialyzer and pack or environment is preferably carbon dioxide.

The term "gas impermeable" means materials that are impermeable to the controlled atmosphere, while the term "gas-permeable" envelope materials

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means that are permeable to the controlled atmosphere and the sterilizing gas.

Dialyzers of the dry type as used in the present application are typically sterilized by methods known per se with sterilizing agents such as ethylene oxide gas. The sterilization can be carried out with the single cover with a permeable zone or with the double cover pack, wherein the inner pack unit can be placed inside the outer open cover and the unit can be completely sterilized. After sterilization, the ethylene oxide gas in the dialyzer unit is completely replaced, usually with aseptic air during a "degassing period". Typically, artificial kidney dialyzers are degassed for several days, for example as long as about 15 to 20 days, in order to ensure that all ethylene oxide residues are removed. The term "sterilization ¹¹ or" sterilization "as used herein means the initial sterilization as well irgendx ^ elk subsequent time required to remove any toxic residues of the sterilization material before the units and packages are then subjected to evacuation. Furthermore, For example, the atmosphere evacuated from the packing unit in the claimed method can be a sterilizing gas and / or air. Radiation sterilization methods that do not affect the dialyzer membranes can also be used and the evacuation can be carried out with or without waiting time, or the unit can directly sealed with the controlled atmosphere Dialyzers

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of the dry type, which are sterilized with ethylene oxide, by irradiation or other methods, and which Contain inlet and outlet openings which are covered with a gas-permeable material, for example with a Insert or with a cap, can be in an open gas-impermeable Sheath can be placed and the kidney unit and sheath evacuated (or possibly sterilized first) and then filled and sealed with a controlled atmosphere will.

Sealable flexible packing materials are used as gas-impermeable packing materials from which the envelopes are produced or hard or rigid materials which are generally impermeable to moisture are used. Suitable gas-impermeable materials include, for example, synthetic plastic laminates, metal foils or laminates or Films with insulating layers of metal, for example foils. Mylar is a well known polyester film that is useful can be coated with a metal foil insulating layer. Other materials such as laminates made of polyester and polyethylene and coextrudates made of nylon and Surlyn, are also fully available. Casings, containing a laminated polyethylene and Surlyn material are preferred. Other materials like polyethylene can also be used as gas-impermeable materials, provided that materials with a sufficient thickness can be used. From a cost standpoint, these are generally disadvantageous and relatively inexpensive thin laminates are available. A laminate material made from Mylar, Low Density Polyethylene, and Surlyn that

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containing a metal foil insulating layer for insulation is particularly preferred.

Gas-impermeable envelopes can also be made with some of the materials mentioned above that are deformable when exposed to heat and other materials such as polypropylene or styrene can be made. The ones in the warmth Deformable envelopes typically contain a suitable insulating coating, which is optionally against the controlled atmosphere is impermeable. These and various other materials used as a gas-impermeable envelope can be used, as well as the methods for varying the envelope thickness or insulating coatings for The person skilled in the art is familiar with controlling the permeability.

The inner casing of the double pack dialyzer and the gas-permeable material that covers the openings of the dialyzer covered can be made of the same materials as the gas-permeable zone. Such materials should be permeable to the sterilizing gases and the controlled atmosphere and they can be made of such materials, such as permeable papers or plastics. The inner sheath can also be made from the the same gas-impermeable material as the outer sheath be made, as long as a gas-permeable material on the inner sheath Zone is provided. A gas-impermeable envelope which is provided with a gas-permeable zone is preferred is used as an inner cladding.

The gas-permeable materials, for example the gas-permeable zones, are typically made of papers or syn-

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synthetic plastic materials with controlled porosity and are permeable to the sterilization gases and the controlled atmosphere. Such Papers or plastic materials also serve as microbial insulating layers, so that the sterility and the aseptic condition of the dialyzer is maintained. Materials of this type are available and include by spinning associated polyolefins such as Tyver and various controlled porosity papers. The professional becomes can easily select these and other materials that can be used for this purpose.

The gas-impermeable envelope, which is a gas-permeable zone and which is used to manufacture a dialyzer packaged with a single casing The permeable zones are placed in an area where they are easily sealed and, if necessary, subsequently removed can be.

The size and shape of the inner or outer wrappings is not critical. They can come in the form of flexible pillows or Bags, sleeves, hard or semi-hard cans or canisters or pipes are present. Flexible cushions or pockets are preferred because they are easy to install and save costs. Relatively hard, formed in the warmth Enclosures that have a gas-permeable lid can be used for protective purposes or for the production of suitable, light storable container can be used. When using thermally deformed envelopes with a permeable zone that is flexible or has been formed in the heat can also be gas-impermeable via the permeable zone Materials are attached in a sealing relationship

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with the gas-impermeable envelope, a sealed gas impermeable pack is formed which contains therein a dialyzer and a controlled atmosphere. All the envelopes are easily sealable and typically are sealed in the package for easy opening Pack facilities provided. The envelopes are preferably sufficiently strong that they cannot be torn off or resist breaking and puncturing.

Typically, an artificial kidney dialyzer is used at using hollow fiber membranes in an inner sheath packaged containing a pouch or pillow (made from a laminate material of polyethylene low density and surlyn) that are about 36 inches long and is about 17 cm wide. This bag or this cushion contains a gas-permeable zone made of spun polyolefin material (Tyvek) with a diameter of about 7.60 cm. The gas-impermeable outer casing is made of the same material and slightly larger (about AO cm χ about 19.5 cm), so that the dialyzer can be accommodated in the inner pack.

If the dialyzer is encased in a single envelope, a pouch or pillow can be approximately 48 cm long with a gas-permeable zone (Tyvek) with a diameter of 7.60 cm, which is arranged so that it is separated from the rest the pack containing the dialyzer can be sealed. The gas-permeable area is preferably attached to one end of the envelope, an additional envelope area of about 12.70 cm is for the permeable zone available. When the bag or the pillow

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once sealed, the sterilization, evacuation and steps of filling the bag or cushion with controlled atmosphere through the permeable zone will. Once the controlled atmosphere is introduced into the pack, a second seal occurs, which divides the pack into two parts along the pocket or pillow between the dialyzer and the Area containing the permeable zone so that the permeable zone is separated from the remainder of the pack containing the dialyzer which is thus isolated within a gas-impermeable bag or a gas-impermeable cushion, completely separated is. The portion containing the permeable zone can optionally be removed from the packaged dialyzer but this is not required.

Those skilled in the art will make many changes in the bag or pillow or wrap, location, style and size the permeable zone in the bag or the pillow or the envelope can carry out and various embodiments dialyzers that contain a controlled atmosphere. The stages of the first Sealing, sterilizing, evacuating, filling with controlled atmosphere and the following Sealing for both single-jacketed and double-jacketed dialyzers and alterations these procedures are also easy to perform and can be carried out by those skilled in the art of packaging.

Although the stages can be performed manually with each unit, semiautomatic ones can also be performed Procedures are used. For example, you can

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Completely packed units, for example single or double packed sterilized dialyzers, easily evacuate, fill with a controlled atmosphere and seal to form a gas impermeable package using a vacuum and gas backfill packing machine. In typical procedures, three sterilized dialyzers are individually packaged in a gas-impermeable inner bag or pillow containing a gas-permeable zone and an open gas-impermeable outer bag or pillow is placed in the vacuum chamber of the machine and the bags or pillows and dialyzers are at evacuated under reduced pressure of about 73.7 mm of mercury. The evacuation time is generally 60 seconds, but shorter or longer times may be required depending on such conditions as dialyzer sizes and shapes. Carbon dioxide gas is then injected into the chamber, the dialyzers and the inner and outer pillows or pouches are completely purged. The COp pressure is maintained at about atmospheric pressure. After the chamber is completely filled or flooded with COp, the open outer cushions or pockets are sealed with an impulse sealing mechanism contained in the chamber. To remove excess COp, the chamber is then vented before sealing and the gas-impermeable, packaged dialyzers containing COp are removed from it.

From the above description it can be seen that according to the invention a new pack for packing objects, where sterility is required is created. Any item that requires sterility can be

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how other medical devices or devices are packaged as described above.

According to the invention, a new packaged kidney dialyzer is provided created, which contains a controlled atmosphere, the suction or starting of the dialyzer, for example with a saline solution, in a simple, fast and expedient way without the risk of contamination .

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Claims (16)

Patent attorneys Dipl.-Ing. H. Weickmann, Dipl.-Phys. Dr. K. Fincke Dipl.-Ing. FAWeickmann, Dipl.-Chem. B. Huber 8 MUNICH 86, DEN PO Box 860 820 MÖHLSTRASSE 22, CALL NUMBER 98 3921/22 17,969-F Claims { 1. A method for producing a gas-impermeable ^ pack by sealing an object in an envelope or a housing which is impermeable to gas, characterized in that the following steps are carried out: (a) in the envelope or the housing creates a gas-permeable zone, (b) sterilizing the package, (c) evacuating the package, (d) introducing a controlled gas atmosphere into the package, and (e) the package into a first part containing a gas-permeable zone and a the second part containing the article sealingly divides to form a gas impermeable package containing the article and a controlled gas atmosphere. 2. A method of making a gas impermeable packing incorporating a kidney dialyzer and a controlled one Contains atmosphere, characterized in that the following steps are carried out: (a) a sterilized dialyzer that contains inlet and outlet ports that are filled with a permeable material 709t43 / 088A ORIGINAL INSPECTED - 2 - 271617h are covered, whereby a gas-permeable zone is created, in an open gas-impermeable envelope or an open gas-impermeable housing provides, (b) the dialyzer and the wrapping bzv /. evacuates the enclosure, (c) a controlled atmosphere in the enclosure, and conducts the dialyzer and (d) seals the casing or the housing to form a gas-impermeable packing. 3- The method according to claim 1 or 2, characterized in that for the housing or the Sheath a sealable flexible or rigid or hard material is selected. 4. The method according to claim 3> characterized in that the material is a deformable in the heat synthetic resinous material or a laminate that is a thermoplastic synthetic resinous Contains material and a metal insulation layer. 5. The method according to claim 1 or 2, characterized in that the casing or the housing is a laminate comprising a polyester film, a polyethylene layer low density, a metal insulation layer and a layer of a polymeric resinous Contains ionomers of ethylene. 6. The method according to claim 1 or 2, characterized in that for the permeable zone a controlled porosity material is selected. 709 6 43/0884 7. The method according to claim 6, characterized in that paper or a permeable synthetic resinous material is selected as the material with controlled porosity and that the permeable zone serves as a microbial boundary. 8. The method according to any one of claims 1 to 7, characterized in that the object is an artificial kidney. 9. A method for producing a gas-impermeable package which contains an object and a controlled atmosphere , characterized in that the following steps are carried out: (a) the object in a first envelope or a first housing which or which is opposite to gas is permeable, seals, (b) sterilizes the sealed object, (c) covers the sealed and sterilized object with a second gas-impermeable envelope or a second gas-impermeable housing to form an outer envelope housing around the sealed object, (d) the sealed Ge The object and the outer envelope are evacuated, (e) a controlled atmosphere is introduced into the outer envelope and into the sealed object, and (f) the outer envelope seals to form the gas-impermeable packing. 10. The method according to claim 9, characterized in that a sealable flexible or rigid or hard material is selected for the first or second envelope. 709843/0884 11. The method according to claim 1.0, characterized in that the material is a deformable in the heat synthetic resinous material or a laminate that is a layer of a thermoplastic contains resinous material and a metal boundary layer. 12. The method according to claim 9, 10 or 11, characterized in that the first envelope is a gas-impermeable Material with a gas-permeable zone, which also serves as a microbial boundary, and that the gas-permeable zone a material with controlled porosity includes. 13. The method according to claim 12, characterized in that the material with controlled porosity Paper or permeable synthetic resinous material is used. 14. The method according to claim 9, 10 or 11, characterized in that the first envelope or the first housing is a heat-deformed base envelope which contains a gas-permeable cover. 15. The method according to any one of the preceding claims, characterized in that the sterilization with ethylene oxide and that the controlled atmosphere is carbon dioxide. 16. Gas-impermeable pack, characterized in that it according to one of the methods of Claims 1 to 15 was made. 709843/0884