US20130206634A1

US20130206634A1 - Package comprising a sterilized content

Info

Publication number: US20130206634A1
Application number: US13/704,712
Authority: US
Inventors: Pascal Maria Hubert Pierre Tijssen
Original assignee: DSM IP Assets BV
Current assignee: DSM IP Assets BV
Priority date: 2010-06-16
Filing date: 2011-06-14
Publication date: 2013-08-15
Also published as: EP2582402A1; JP2013534885A; CN102946909A; WO2011157705A1

Abstract

A package comprising a sterilized content, characterized in that at least a part of the package wall has a moisture vapor transmission rate (MVTR) of between 100 and 1500 g/m²·day measured according to ASTM E96/E96M-05 procedure B, at 38° C. and 50% Relative Humidity.

Description

The invention relates to a package comprising a sterilized content, the package having at least one layer of a polymer composition.
Such a package is known from EP-398316, wherein a package for the storage of a medical container holding a medical fluid is described. Examples of such containers include blood bags containing a solution of an anticoagulant or transfusion bags, containing a transfusion solution, the solution for example comprising nutrition components or a medicament. It is also possible that the package contains a suture, a combination of a suture and a needle or even one or more medical instruments.
It is advantageous to first fill the package with the content to be sterilized, close the package and than sterilize the package with the content. Very often sterilization is carried out in an autoclave, filled with water and/or steam at elevated pressure and temperature.
A problem with the package of EP-398316 is that during the sterilization water penetrates through the package wall into the package. After cooling down the water is present as water drops. It is however highly unwanted that the content, for example a blood bag or an instrument is wet when taken out of the package. This is because it gives the impression to personnel handling the bag and the content, that the bag was not properly sealed and that the content is not sterile.
In U.S. Pat. No. 4,537,305 a package is proposed consisting of a multi-layer polymer film structure, wherein one of the layers has barrier properties for water. The package is complicated, because of the multi-layer structure. Further it is still possible that water is present in the package, for example water of the solution of the anticoagulant, that penetrates trough the wall of a blood bag that is stored in the package.
In JP-5084281 a package for sterilization of blood bags is proposed consisting of two compartments having a membrane between the two compartments. A blood bag is placed in one of the compartments and that compartment is closed. The blood bag and the package are sterilized in a steam atmosphere and steam penetrates in the open compartment of the package and through the membrane into the closed compartment comprising the blood bag. After the sterilization the package is kept for a period of several hours at an elevated temperature to remove the water again from the package through the membrane and the opening of the second compartment. Finally the second compartment is closed as well.
This package is very complicated, and a danger exists that during the drying process bacteria enter the open compartment and penetrate through the membrane, especially if small defects are present in the membrane. Furthermore the procedure of sterilization is complicated, since first a lot of water is allowed to penetrate in the compartment, but has to be removed again afterwards.
In some occasions packages having a non-woven porous fleece as package wall are used. These walls have a high permeability for water, so that after the sterilization the content of the package may be dried easily. However there is insufficient guarantee that the package provides a full barrier small bacteria and viruses.
Object of the invention is to provide a package for sterilization and storage of a content that is simple and allows a straightforward sterilization process.
Surprisingly this object is obtained if at least a part of the package wall has a moisture vapor transmission rate (MVTR) of between 100 and 1500 g/m²·day measured according to ASTM E96/E96M-05 procedure B, at 38° C. and 50% Relative Humidity.
It is now possible that the package contains only one compartment and no extra barrier layer is needed in the package. Furthermore the sterilization process is very simple and straightforward. The content, for example a blood bag, is placed in the package and the package is closed. The package may be placed in an autoclave and is sterilized with steam. Because of the limited permeability and the relative short time wherein the sterilization takes place only a very limited amount of water penetrates into the package. After sterilization, because of the permeability for water vapor, a drying step under mild conditions fulfills to release the water from the package. It might even be possible that, if stored in a relatively dry room, the water is released from the package, without special treatment.
Preferably the MVTR is at least 125 g/m²·day, more preferably at least 150 g/m²·day, even more preferably at least 175 g/m²·day.
Preferably the MVTR is at most 1250 g/m²·day, more preferably at most 1000 g/m²·day, even more preferably at most 750 g/m²·day, most preferably at most 500 g/m²·day.
It is possible that a part of the container wall has an MVTR different from the value defined above. In that case preferably that part of the wall has a MVTR that is lower than the MVTR defined above. Preferably the entire wall of the package has the same structure and composition, so that the MVTR has the same or about the same value for the whole of the container.
The package might be a container, for example as disclosed in EP-398316. Preferably the package is a bag. This is because a bag fulfills in general the demands posed on the package during sterilization, transport and storage and a bag is easy to produce from all kind of polymer compositions.
Polymers that are suitable for use in the package wall according to the invention include polyamides, for example PA-6, PA-66, PA-666.
Preferably the polymer is a polar thermoplastic elastomer.
A thermoplastic elastomer is a rubbery material with the processing characteristics of a conventional thermoplastic and below its melting or softening temperature the performance properties of a conventional thermoset rubber. Thermoplastic elastomers are described in Handbook of Thermoplastic Elastomers, second edition, Van Nostrand Reinhold, New York (ISBN 0-442-29184-1).
The polar thermoplastic elastomer preferably contains oxygen (O) and/or nitrogen (N) atoms. Preferably the polar thermoplastic elastomer contains at least one N or one O atom at every 8 C atoms, preferably at every 6 C-atoms, more preferably at every 4 C atoms. Good examples of polar groups contained in the polar thermoplastic elastomer are —NH—, —O—, —COO—, and —CO—NH— groups.
Good examples of polar thermoplastic elastomers are polyester based thermoplastic elastomers, polyamide based thermoplastic elastomers and polyurethanes. Examples of polyester based thermoplastic elastomers include polyetherester elastomers, polyurethane ester elastomers, polycarbonate ester elastomers.
Preferably thermoplastic copolyetherester elastomers are used.
This is because a package is obtained that is flexible and yet strong at both the high temperatures of the sterilization process and low temperatures that might occur during transport and storage. Furthermore a package with no or little defects is obtained, whereas in the package of the state of the art pinholes may be present that let bacteria through to infect the content of the package. Also a package with a high transparency can be obtained. This is desirable, because personnel working with the package can easily recognize the content. Furthermore the antistatic properties of the package are very favorable. This is important, because discharge of static electricity might otherwise damage the package, for example cause pinholes in the wall of the package, so that again bacteria may penetrate into the package.
The thermoplastic copolyetherester elastomer suitably contains hard segments that are built up from repeating units derived from at least one alkylene diol and at least one aromatic dicarboxylic acid or an ester thereof. As alternative to segment, also the term block is being used. The alkylene diol may be a linear or a cycloaliphatic alkylene diol. The linear or cycloaliphatic alkylene diol contains generally 2-6 C-atoms, preferably 2-4 C-atoms. Examples thereof include ethylene glycol, propylene diol and butylene diol. Preferably propylene diol or butylene diol are used, more preferably 1,4-butylene diol. Examples of suitable aromatic dicarboxylic acids include terephthalic acid, 2,6-naphthalenedicarboxylic acid, 4,4′-biphenyldicarboxylic acid or combinations of these. The advantage thereof is that the resulting polyester is generally semi-crystalline with a melting point of above 150, preferably above 175, and more preferably of above 190° C. The hard segments may optionally further contain a minor amount of units derived from other dicarboxylic acids, for example isophthalic acid, which generally lowers the melting point of the polyester. The amount of other dicarboxylic acids is preferably limited to not more than 10 mol %, more preferably not more than 5 mol %, so as to ensure that, among other things, the crystallization behaviour of the copolyetherester is not adversely affected. The hard segment is preferably built up from ethylene terephthalate, propylene terephthalate, and in particular from butylene terephthalate as repeating units. Advantages of these readily available units include favourable crystallisation behaviour and a high melting point, resulting in copolyetheresters with good processing properties, excellent thermal and chemical resistance and good puncture resistance.
Suitable aliphatic polyether soft segments in the thermoplastic copolyetherester elastomer are flexible polyethers that are substantially amorphous and have a glass-transition temperature (T_g) of below 0° C. Preferably, the T_gis below −20° C., more preferably below −40, and most preferably below −50° C. The molar mass of the segments may vary within a wide range, but preferably the molar mass is chosen between 400 and 6000, more preferably between 500 and 4000, and most preferably between 750 and 3000 g/mol. Suitable aliphatic polyethers include a poly(alkylene oxide)diol derived from an alkylene oxide of 2-6 C-atoms, preferably 2-4 C-atoms, or combinations thereof. Examples include poly(ethylene oxide)diol, poly(tetramethylene oxide)diol or poly(tetrahydrofuran)diol, poly(neopentylene oxide-co-tetramethylene oxide)diol and poly(propylene oxide)diol. In one preferred embodiment the thermoplastic polyetherester elastomer contains as polyether segments ethylene oxide-terminated poly(propylene oxide)diol segments.
Good results are obtained if the thermoplastic copolyetherester elastomer contains chain branching agents. Suitable chain branching agents include e.g. trimellitic acid, trimellitic acid anhydride and trimethylol propane. The amount and type of chain extension or branching agent is chosen such that a block copolyester of desirable melt viscosity is obtained. In general, the amount of a chain branching agent will not be higher than 6.0 equivalents per 100 moles of dicarboxylic acids presenting the copolyetherester. The copolyetherester can further contain the usual catalysts and stabilisers.
Examples and preparation of copolyetheresters are for example described in Handbook of Thermoplastics, ed. O. Olabishi, Chapter 17, Marcel Dekker Inc., New York 1997, ISBN 0-8247-9797-3, in Thermoplastic Elastomers, 2nd Ed, Chapter 8, Carl Hanser Verlag (1996), ISBN 1-56990-205-4, in Encyclopedia of Polymer Science and Engineering, Vol. 12, Wiley & Sons, New York (1988), ISBN 0-471-80944, p. 75-117, and the references cited therein.
Particularly preferred is a copolyetherester with hard segments built up from butylene terephthalate units and soft segments derived from ethylene oxide-terminated poly(propylene oxide)diol.
Most preferably the copolyetherester elastomer has been subjected to a post condensation process. Post condensation of the elastomer is a suitable and economic way of obtaining a high molecular weight, resulting in an elastomer having the desired viscosity, necessary for obtaining the good processability of the composition, to obtain the tubular film according to the invention. Most suitable is solid state post condensation. In this process the solid copolyetherester elastomer is heated to about 10-20° C. below its melting point in a tumble dryer. A vacuum is applied to remove condensation products from the elastomer.
The package wall might be of a multilayer structure. Preferably the package wall is of a two layer structure, a first layer that is a base layer containing one or more of the polymers described above and a second layer of a polymer composition being capable of sealing the bag. Examples of a polymer being capable of sealing the bag include PA-6,6.6, polyvinyl acetate (PVAc), copolymers of ethylene with (meth)acrylates, or vinyl alcohol. These polymers also provide a layer with a suitable MVTR, so that the MVTR of the entire package wall is in the desired area. The second layer preferably is thinner than the first layer and the composition of the second layer preferably has a melting point of 20° C., more preferably of 30° below the melting point of the composition of the base layer. Sealing is normally carried out by applying heat and pressure to the package.
It is however also possible that the package wall is a one layer structure, so that the package wall consists of the base layer. In that case the package for example has to be closed by welding or by a applying a sealing agent.
It is also possible that the package wall next to the base layer an outer layer of a polymer composition capable of acting as anti-blocking layer to prevent packages to stick together during storage of the package. A good example of an anti-blocking layer is a layer of PBT or PA-6. Preferably PA-6 is used in the anti-blocking layer.
The MVTR of the package wall increases with decreasing thickness of the layers. However in choosing the thickness of the layer is also important to consider the other functions of the layer. If the base layer becomes to thin, the package wall might loose its strength. A suitable thickness for the base layer therefore is between 20 and 80 microns, preferably between 30 and 60 microns. The thickness of the layer capable of sealing the package may be between 10 and 30 microns, the anti-blocking layer may be between 5 and 15 microns.
The base layer of the packaging according to the invention consists preferably of a blend of PA-6 and a thermoplastic copolyetherester preferably in a ratio PA-6: thermoplastic copolyetherester of between 90:10 and 50:50. Of course next to the PA-6 and the thermoplastic copolyetherester the blend may contain non-polymeric additives. A base layer of such a blend is very strong, has the desired MVTR and has good-anti-blocking properties, so that a special anti-blocking layer is not necessary any more.
For the production of the package the processes for producing packages of polymer compositions that are well-known to the person skilled in the art may be used.
In case the package is a bag, the bags may for example be produced by blowing a film and cutting and welding the blown film into bags. Another possibility is the produce a film with a slit die, to weld the films into a tubular film and to produce in the same manner the bags by cutting and welding.
Sterilization process may comprise the step of placing the content to be sterilized into the package, sterilizing the package and its content in a steam autoclave, drying of the package and its content by a heat treatment.
A drying time of less than 5 hours is regarded to be an acceptable drying time. Longer drying times are giving logistical and economic drawbacks.
It is also possible that the sterilization is carried out by using a gas, for example ethylene oxide gas.
The invention will now be further elucidated with reference to the following examples and comparative examples, without being limited hereto

EXAMPLES

For the experiments 60 micron thick film were used consisting of the following polymer compositions:

Example 1

composition=Arnitel® EM400 (co-polyether-ester)

Example 2

composition 2=Arnitel® VT3108 (co-polyether-ester)

Example 3

composition 3=blend of 90% Akulon® S240C (polyamide 6,6)+10% Arnitel® VT3108

Example 4

composition 4=blend of 70% Akulon® F136 (polyamide 6)+30% Arnitel® VT3108

Example 5

composition 5=Akulon® F136

Comparative Experiment A

composition A=Arnite® A02 306 (poly-ethylene-terephthalate)

Comparative Experiment B

composition B=BOPP (Bi-axial-Oriented-PolyPropylene)
Polymer compositions 1-6 are available from DSM Engineering Plastics and composition 7 was a standard BOPP film.
The moisture vapour transmission rate of these films was tested using a CTS Type C+10/350 climate control chamber and the samples where tested according to ASTM E96/E96M-05 Procedure B at 38° C. and 50% Relative Humidity.

TABLE 1

Moisture vapour transmission rate of films 1 through 7

Thickness	MVTR	MVTR
Microns	Grams/M²· Day	Grams · mm/M²· Day

Example 1	57	578	33.0
Example 2	61	977	59.6
Example 3	58	121	7.0
Example 4	60	173	10.4
Example 5	62	102	6.3
Comparative	59	66	3.9
Experiment A
Comparative	60	2	0.1
Experiment B

From these films pouches were made by means of heat sealing. The size of the pouches was based on an A4 paper sheet so the total pouch surface is 21 cm*29.5 cm*2=1239 CM²which is 0.1239 M².
In order to simulate the penetration of water during an autoclave sterilization process we placed 2 millilitres of water into the pre-sealed bags and closed the last seal by means of heat sealing. The sealed bags where placed in a circulation oven (Vötsch Type NTU 60/60) at 38° C. To check the drying speed of the pouches the bags were removed every half hour from the oven and placed in for 30 seconds in a refrigerator. Subsequently the bags were visually checked for condensation of water at the inside of the bag. The number of hours before the bags were free of condensation is regarded to be the measure of effectiveness to drive of water. The results are listed in table 2.

TABLE 2

Time before pouches were dry.

	Hours

	Example 1	1.0
	Example 2	0.5
	Example 3	3.5
	Example 4	2.5
	Example 5	4.0
	Comparative Experiment A	7.0
	Comparative Experiment B	>24

Claims

1. A package comprising a sterilized content, characterized in that at least a part of the package wall has a moisture vapor transmission rate (MVTR) of between 100 and 1500 g/m²·day measured according to ASTM E96/E96M-05 procedure B, at 38° C. and 50% Relative Humidity.

2. A package according to claim 1, characterized in that the MVTR is at least 100 g/m²·day.

3. A package according to claim 1, characterized in that the MVTR is at least 150 g/m²·day.

4. A package according to claim 1, characterized in that the MVTR is at most 1250 g/m²·day.

5. A package according to claim 1, characterized in that the MVTR is at most 1000 g/m²·day.

6. Package according to claim 1, characterized in that PA-6, PA-66, PA-666, a thermoplastic elastomer are used in the package wall.

7. Package according to claim 6, characterized in that as the thermoplastic elastomer a thermoplastic elastomer with at least one N and/or one O at every 8 C atoms is used.

8. Package according to claim 6, characterized in that the thermoplastic elastomer is copolyetherester.

9. Package according to claim 1, characterized in that the package wall contains or consists of a base layer consisting of a blend of Pa-6 and the copolyetherester.