Tubular multilayered polymerfilm

The present invention is a sterilizable coextruded polymer composite tubular film, the use of these tubular films for the production of peelable secondary packaging for containers containing, for example, drugs or infusion solutions as well as the packaging thus obtained.

Solutions, suspensions, solids or mixtures for parenteralen-, enteralen- or tube feeding are usually bottled in the prior art in various types of containers under sterile conditions. Here, the use of bags that contain the mentioned ingredients, widely used in the prior art. The individual ingredients are partly premixed and partly lie however the ingredients in separate spatial arrangements before, so that a mixture of the ingredients is often done only immediately before use at the bedside of the patient.

The pouch case included removal devices for sterile as possible remove the contents. If, however, also be a sterile outer surface of the container and in particular the sterility of the removal devices is required, it is necessary to provide said containers with an outer package, which ensures sterility.

Thus, an outer package made of polyvinylidene chloride copolymers (PVDC) has become established in the prior art, which, however, is not suitable to ensure the sterility of the bag surface and of the removal device. However, a disadvantage of the use of polyvinylidene chloride is not environmentally friendly chlorine content of the polyvinylidene chloride copolymer, that, moreover, not be sterilized with usual methods. However, the excellent permeabilities to gas, water vapor, flavorings and fat under dry and wet conditions outweighed the recycling problems in the past.

In the prior art other materials for corresponding barrier layers (barrier polymers) are known. Thus, in Ullmann's Encyclopedia of Industrial Chemistry, 5th Edition, Volume 11, Chapter 6.5.10. in addition to PVDC also polyvinyl alcohol and ethylene-vinyl alcohol copolymers as a barrier layer described.

In ethylene-vinyl alcohol copolymers, the moisture sensitivity of the polyvinyl alcohol is reduced by the copolymerization with ethylene. The usual vinyl alcohol content is 60 to 82% corresponding to an ethylene content of 18 to 40%. In Chapter 6.5.12 polymer composites are described as a single layer of a polymer with the requirements for the product to be packaged is not accessible for many applications. Inter alia, the coextrusion of different polymers is described, for example, to improve the thermal properties or the barrier properties here.

WO 95/26268 describes a multilayer composite sheet comprising at least one layer sequence which includes a heterophase polypropylene (co) polymer / bonding layer // EVOH / adhesive layer / polyolefin layer, the heterophase polypropylene (co) polymer of a homopolymer of propylene or a copolymer of propylene with ethylene and / or an alpha-olefin consists.

The problem of the present invention is therefore to provide a sterilizable coextruded polymer composite tubular film for packaging containers containing solutions, suspensions, solids or mixtures for parenteralen-, enteralen- or tube feeding, optionally in a separate spatial arrangement of the ingredients, which is suitable to ensure a sterile outer surface of the container and in particular the sterility of the sampling devices.

The aforementioned problem of the invention is achieved by a sterilizable coextruded polymer composite tubular film for packaging containers containing solutions, suspensions, solids or mixtures for parenteralen-, enteralen- or tube feeding, optionally in a separate spatial arrangement of the ingredients with a three-layer structure of tubular film at a layer sequence<ul><li>a) polypropylene homopolymer,</li><li>b) ethylene-vinyl alcohol copolymer having an ethylene content from 27 to 38 mol .-% and</li><li>c form) homophasiges polypropylene homopolymer or polypropylene copolymer which is suitable, the inside of a Umbeutels of the container.</li></ul>

Using the present invention, it is possible to produce tubular films and it sterilizable outer packaging of the said container, in particular bags in multilayer coextrusion blow molding, which make environmentally safe disposal possible. In addition, it is possible for the container that contains the ingredients to bring prior to sterilization in the outer bag and this sterilized together with the outer package. Apart from a sterilization of the surface of the container is achieved also a sterilization of the removal device. Besides the common sterilization of the outer package forming polymer composite tubular film and of the container, the separate sterilization and subsequent packaging of the container in the bag is possible. The bag thus obtained are heat-sealable.

Core of the three-layered layer structure of the invention, the blown film is the ethylene-vinyl alcohol copolymer layer with a defined ethylene content of 27 to 38 wt .-%, in particular Mol .-%. Namely, the ethylene content is chosen too high, the ethylene-vinyl alcohol copolymer layer is destroyed in the usual steam sterilization and looses its barrier properties for gases, so that the problem of the invention can not be solved in a satisfactory manner.

Tests have shown that the desired product properties are particularly pronounced at a level 29-32%.

Particularly preferred according to the present invention is therefore to adjust the ethylene content of the ethylene-vinyl alcohol copolymer in the range from 29 to 32 wt .-%, especially mol .-%, since a particularly low gas permeability is observed. In addition, the sterilizability and the core layer stability of the layer structure according to the invention is marked in a special way within this range said value.

The ethylene-vinyl alcohol copolymer layer b) is coextruded with the polypropylene homopolymer layer a), which should in the present invention have a layer thickness of 20 to 40 microns, especially 25 to 35 microns. These polypropylene homopolymer layer protects the polyvinyl alcohol of the core layer b) from moisture and gives the overall structure of the necessary thermal stability due to the high softening point of the polypropylene homopolymer, which is to settle above the usual sterilization temperatures.

The homophasige polypropylene homopolymer or polypropylene copolymer layer c), which is adapted to form the inside of a Umbeutels of said container, should preferably have a layer thickness of 30 to 50 .mu.m, in particular 35 to 45 .mu.m. Again, the provision of a material with a high softening point is necessary, which is above the usual sterilization temperatures. This layer of substantially polypropylene protects the polyvinyl alcohol component of the core layer b) from moisture and gives the overall structure the required mechanical stability.

In the case of the use of polypropylene copolymer, the random copolymer consists of propylene next to the component, in particular of ethylene, which may be contained in amounts of 2 to 5 wt .-% in the copolymers.

The polypropylene homopolymer layer a) may optionally contain 0.5 to 2 wt .-% of an absorbing agent, in particular oxygen and / or hydrogen sulfide, with the use of Fe₃O₄ in the sense of the present invention particularly preferred.

The method of choice for producing the inventive tubular film is known per se method of multilayer coextrusion-blowing.

Another embodiment of the present invention consists in the use of the above tubular film for producing peelable secondary packaging of containers containing solutions, suspensions, solids or mixtures for parenteralen-, enteralen- or tube feeding, optionally in a separate spatial arrangement of the ingredients.

The special design of the coextruded polymer composite tubular film according to the invention makes the sterilization of the tubular film in the form of secondary packaging by the usual sterilization procedures possible so that, as mentioned above, the sterility of the container outside and the removal devices are guaranteed up to the bedside of the patient.

Preferred sterilization processes, sterilization at a temperature of 121 ° C and a period of time, the sterility in the autoclave by the steam type or a water cascade guarantees or sterilization with ethylene oxide.

The tubular film material according to the invention is heat sealable and peelable, so that can be produced with the inventive tubular film surrounding bag, in particular by heat sealing, which can be opened along sealing seams again.

Accordingly, another embodiment of the present invention in peelable sterilizable outer packaging containers containing solutions, suspensions, solids or mixtures for parenteralen-, enteralen- or tube feeding, optionally in a separate spatial arrangement of the ingredients with a three-layered structure of the tubular film packaging.

In the prior art of parenteral nutrition oxygen absorbers have been widely employed to protect the ingredients from oxygen. Under the name "Ageless" is for example, an absorbent material based on iron salts is commercially available which simultaneously produces in addition to a reduction of the oxygen content, a reduction of the content of hydrogen sulfide, which originates in usual sterilization methods from sulfur-containing ingredients.

embodiments

Comparative Example 1

A 80 liter batch of 0.5 g / l Na₂S₂O₅ according to 337 mg / l SO ₂ was approximately 280 bags of a multilayer film (polyamide 11 / polypropylene; V90 B. Braun) filled with 200 ml of solution and sterilized at 121 ° C over 15 min without outer bag.

example 1

90 bags of Comparative Example 1 are provided with an outer bag, the layer sequence according to the invention from 28 micron polypropylene homopolymer having a melt flow index MFI (2, 16/230) of 1.9, a flexural modulus of 1400 MPa and a Charpy impact strength measured at 23 ° C 6 kJ / m², 26 microns of an ethylene-vinyl alcohol copolymer having an ethylene content of 32 mol .-% and 42 microns of a random copolymer of propylene / ethylene having a melt index of 1.8 and a flexural modulus of 900 MPa at a Charpy impact strength measured at a temperature of 23 ° C of 8 kJ / m² included. Here, the layers each by 6 microns Orevac®-PPC, manufactured by Atochem, connected. The outer bag, ie the tubular film obtained by multilayer coextrusion blow molding of said materials. The outer bag was closed by per se known heat-sealing process.

The mixture was then sterilized as in Comparative Example 1st

Half of this bag was stored at room temperature or at + 40 ° C. After the time indicated in Table 1 was an enzymatic Sulfitbestimmung, each with 5 bags per variant and storage temperature.

Table 1 gives the data obtained again.

example 2

Analogously to Example 1 90 V90-bags were wrapped prior to sterilization to the outer bag of Example 1 and also stored at the temperatures listed in the example first

With the stored at +40 ° C variants a ion chromatographic sulfate determination was carried out after sulfite was not mehrweisbar with three bags. In all variants of the theoretically expected amount of sulfate of 505 mg / l was measured.

Comparative Example 2

The prey referred to in Example 1, half (ie 90 bags) with a commercial Umbeutelmaterial comprising layer sequences saranisiertes (PVDC) PVOH / LDPE / LLDPE, thickness wrapped 88 microns. <tables id="tabl0001" num="0001"><table frame="all"><title>Table 1</title><tgroup cols="4" colsep="1" rowsep="1"><colspec colnum="1" colname="col1" colwidth="39.37mm" /><colspec colnum="2" colname="col2" colwidth="39.37mm" /><colspec colnum="3" colname="col3" colwidth="39.37mm" /><colspec colnum="4" colname="col4" colwidth="39.37mm" /><thead valign="top"><row><entry namest="col1" nameend="col4" align="center">SO₂-contents (Mg / l) of bags with different outer packaging after storage at room temperature and at + 40 ° C * **. Means with standard deviation of each 5 bags per test date.</entry></row><row><entry namest="col1" nameend="col1" /><entry namest="col2" nameend="col2" rowsep="0" align="center">example 1</entry><entry namest="col3" nameend="col3" rowsep="0" align="center">example 2</entry><entry namest="col4" nameend="col4" rowsep="0" align="center">Comparative Example 2</entry></row><row><entry namest="col1" nameend="col1" align="center">Storage time (days)</entry><entry namest="col2" nameend="col2" /><entry namest="col3" nameend="col3" /><entry namest="col4" nameend="col4" /></row></thead><tbody valign="top"><row><entry namest="col1" nameend="col1" align="center">0 *</entry><entry namest="col2" nameend="col2" align="center">206.7 ± 2.3</entry><entry namest="col3" nameend="col3" align="center">193.2 ± 1.9</entry><entry namest="col4" nameend="col4" align="center">206 ± 2.3</entry></row><row><entry namest="col1" nameend="col1" align="center">5</entry><entry namest="col2" nameend="col2" align="center">73.2 ± 20.5</entry><entry namest="col3" nameend="col3" align="center">57.3 ± 14.0</entry><entry namest="col4" nameend="col4" align="center">71.6 ± 19.9</entry></row><row><entry namest="col1" nameend="col1" align="center">11</entry><entry namest="col2" nameend="col2" align="center">34.7 ± 6.9</entry><entry namest="col3" nameend="col3" align="center">32.0 ± 12.4</entry><entry namest="col4" nameend="col4" align="center">36.2 ± 4.9</entry></row><row><entry namest="col1" nameend="col1" align="center">14</entry><entry namest="col2" nameend="col2" align="center">16.1 ± 3.6</entry><entry namest="col3" nameend="col3" align="center">18.9 ± 3.6</entry><entry namest="col4" nameend="col4" align="center">16.0 ± 7.6</entry></row><row><entry namest="col1" nameend="col1" align="center">16</entry><entry namest="col2" nameend="col2" align="center">14.7 ± 2.4</entry><entry namest="col3" nameend="col3" align="center">16.2 ± 4.6</entry><entry namest="col4" nameend="col4" align="center">14.0 ± 3.9</entry></row><row><entry namest="col1" nameend="col1" align="right"> </entry><entry namest="col2" nameend="col2" /><entry namest="col3" nameend="col3" /><entry namest="col4" nameend="col4" /></row><row><entry namest="col1" nameend="col1" align="center">0 **</entry><entry namest="col2" nameend="col2" align="center">206.7 ± 2.3</entry><entry namest="col3" nameend="col3" align="center">193.2 ± 1.9</entry><entry namest="col4" nameend="col4" align="center">206.7 ± 2.3</entry></row><row><entry namest="col1" nameend="col1" align="center">7</entry><entry namest="col2" nameend="col2" align="center">123.9 ± 12.1</entry><entry namest="col3" nameend="col3" align="center">114.4 ± 5.6</entry><entry namest="col4" nameend="col4" align="center">122.7 ± 5.4</entry></row><row><entry namest="col1" nameend="col1" align="center">14</entry><entry namest="col2" nameend="col2" align="center">90.7 ± 9.9</entry><entry namest="col3" nameend="col3" align="center">89.4 ± 7.9</entry><entry namest="col4" nameend="col4" align="center">90.1 ± 5.3</entry></row><row><entry namest="col1" nameend="col1" align="center">90</entry><entry namest="col2" nameend="col2" align="center">42.6 ± 10.1</entry><entry namest="col3" nameend="col3" align="center">28.4 ± 6.5</entry><entry namest="col4" nameend="col4" align="center">29.5 ± 10.3</entry></row></tbody></tgroup></table></tables>

It was found that secondary packaging of the invention are the outer packaging of the prior art with respect to the oxygen permeability at least equivalent or improved. Another advantage of the bag according to the invention, however, is the better environmental impact with respect to the bags of the prior art remarkable.