OA20096A

OA20096A - Film Packaging for Oral Biologics.

Info

Publication number: OA20096A
Application number: OA1201400197
Authority: OA
Inventors: Jürgen Wilke; Christian Kaiser; Peter Schuster
Original assignee: Ceva Santé Animale S.A.
Priority date: 2011-11-07
Filing date: 2012-11-07
Publication date: 2021-12-13

Abstract

The invention relates to a sealable, molded body and the production thereof, as well as a composite film for the formation of the molded body, and the use of the molded body for the packaging of oral biologies, in particular orally applicable vaccines. The composite film comprises two outer layers, one of the outer layers is formed as a sealing layer, or a barrier layer or a carrier layer, and the other outer layer has a rough or uneven or microstructured surface or comprises at least a nonwoven material, an adhesive material, a sticky material or a combination thereof. It is preferred that the composite film is biologically degradable. A molded body, which takes up the biologic or the vaccine, is formed from the composite film by thermoforming, and is then sealed.

Description

The invention relates to a sealable, molded body and the production thereof, as well as a composite film for forming the molded body and the use of the molded body for the packaging of oral biologics, in particular orally applicable vaccines. In preferred embodiments the molded body and/or the composite film are/is biologically degradable.

The problem of oral administration of agents that are biologically effective or effective in veterinary medicine (biologics, particularly vaccines) to wild animais living in the wild or in captivity, domestic animais and house pets has previously not been solved satisfactorily. Effective agents that are in liquid form or must be administered in liquid form represent a particular problem in this respect. A large and important field of application in this respect is vaccination against rabies in wild foxes. Baits hâve been used previously for this, and these baits contain the vaccine in a conventional blister pack enveloped by a solid vehicle substance, to which a bait or attractant or repellent is attached. These types of baits are described, for example, in DE36 11 122 Al or US-A4,861,586.

The blister packs hâve great disadvantages, however. On the one hand, it is easy to separate them from the solid vehicle substance. Thus, the baits are no longer in a form ingested by the targeted animais, as is necessary for oral application of the vaccine. Rather, the animais separate the blister pack and then reject it.

Also, it is difficult to open the blister pack. The fox must bite into the pack in order to perforate the aluminum foil and to reach the content. The content is then taken up in the mouth cavity. In this case, small ingested quantifies are generally sufficient in order to provide an effective immunization. However, the animais will only bite into the bait when it is intact and the blister pack cannot be recognized.

In contrast, this type of bait is completely unsuitable for other wild animais, since they hâve a different food consumption behavior. Thus, raccoons investigate nourishment very precisely and tear it into small pièces, which then bitten into. For anatomical reasons, the form and structure of the mouth cavity does not permit taking up the bait in its entirety.

It is thus an object of the présent invention to create a packaging that overcomes the disadvantages of the prior art for the oral application of biologics to animais.

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BRIEF DESCRIPTION OF THE INVENTION

The subject of the présent invention is a container in the form of a sealable molded body, which is formed from a composite film, whereby the composite film is preferably biologically degradable, provides high barrier properties against water, oxygen, and carbon dioxide, is thermoformable and sterilizable, and has an adhesive layer for hydrophilic substances.

The subject of the présent invention is thus a sealable molded body for the packaging of oral biologics, particularly oral vaccines, formed from at least one composite film, whereby the composite film comprises two outer layers, one of the outer layers is formed as a sealing layer, or a barrier layer or a carrier layer, and the other outer layer has a rough or uneven or microstructured surface or comprises at least a nonwoven material, an adhesive material, a sticky material or a combination thereof.

A preferred embodiment of the subject of the invention is thus a sealable molded body for the packaging of oral biologics, particularly oral vaccines, formed from at least one composite film, whereby the composite film comprises at least three layers, one of the outer layers being formed as a sealing layer, the other outer layer comprising a nonwoven material, and the at least one middle layer being a barrier and/or a carrier layer. In that context it is preferred that the composite film is biologically degradable. It is also preferred that context that the layers are joined with an adhesive layer. This adhesive or adhesive layer may be applied by a laminating or an extruding process, or any other process known in the art, or by a combination of the named processes.

Another subject of the présent invention is a method for the production of a sealable molded body according to the invention as well as its sealing.

The subject of the présent invention is further the composite film itself, whereby the composite film is biologically degradable, provides high barrier properties against water, oxygen, and carbon dioxide, is thermoformable and sterilizable, and has an adhesive layer for hydrophilic substances.

The subject of the présent invention is further the use of a composite film for the production of a molded body for the packaging of biologics, whereby the composite film is biologically degradable, provides high barrier properties against water, oxygen, and carbon dioxide, is thermoformable and sterilizable, and has an adhesive layer for hydrophilic substances.

Finally, still another subject of the présent invention is the use of a sealable moldcd body according to the invention for sealing pharmaceutical sub- stances, especially oral biologics and oral vaccines.

BRIEF DESCRIPTION OF THE DRAWINGS

Figs, la and 1b show embodiment examples of the composite film according to the invention.

Figs. 2a and 2b show further embodiment examples of the composite film according to the invention.

Fig. 3 shows the arrangement of the composite film according to the invention for the structure of an embodiment of a sealable molded body according to the invention.

Figs. 4a, 4b and 4c show another embodiment of a sealable molded body according to the invention, the arrangement of the composite film according to the invention in the formation of the molded body and the molded body in the sealed State.

Fig. 5 shows the resuit of a Differential Scanning Calorimetry (DSC) experiment performed on composite films according to the invention.

DETAILED DESCRIPTION OF THE INVENTION

The subject of the présent invention is a sealable molded body for the pack- aging of oral biologics, particularly oral vaccines, formed from at least one composite film, whereby the composite film comprises two outer layers, one of the outer layers is formed as a sealing layer, or a barrier layer or a carrier layer, and the other outer layer has a rough or uneven or microstructured surface or comprises at least a nonwoven material, an adhesive material, a sticky material or a combination thereof.

In order to overcome the disadvantages in the art a composite film is provided that consists of at least two layers. These two layers may be formed according to processes that are known in the art like extrusion coating or extrusion laminating and other processes or with a combination of the named or known processes. Therefore, a composite film consists of two outer layers, which may be named also as surfaces of the composite film. According to the invention

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One outer layer has properties that enable the layer to undergo a sealing process. This

sealing process may be accomplished by sealing two separate composite films together or by sealing a single composite film after bringing the film into a tube-like form whereby the sealing layer or surface faces itself.

The other outer layer has at least on the surface properties that allow other components, Chemicals or substances to stick or to glue or to adhéré on that surface. In order to provide these properties the other outer layer may be formed, at least on the surface, uneven, or rough, or microstructured. These surface properties may be achieved by processes known in the art, like abrasive processes, corroding processes, roughening processes, or other processes known in the art or by a combination of the known or named processes.

Furthermore, the outer layer may also according to the invention comprise an additional material that is fixed on the surface of the other outer material. This means for example that a nonwoven material is applied on the surface of the outer layer. In other embodiments according to the présent invention there may be applied an adhesive material, a sticky material or a combination thereof.

As a resuit the other outer layer shall hâve a property that is named in rubber industry as ~ provided with good grip or in textile industry having a good hand or handle. It is important and advantageous to provide these properties so that further material may be attached to the sealed mold in order to form a bait that may be used for the application of a biologie to a wild animal, for example.

In order to achieve the properties as described it may be advantageous that the outer layers comprise at least one sub-layer. The sub-layer has advantageously different physical and/or Chemical properties in respect to the original layer. A sub-layer may be présent on one side of the original layer or on both sides of the original layer.

In order to préparé such layers with different sub-layers, known processes are used. Suitable processes hâve been described already and comprise, for example, extrusion coating or extrusion laminationor co-extrusion processes. Processes for métallisation of films and foils are also known in the art and may be combined with the named or known processes in order to obtain a composite film according to the invention.

In an example according to the présent invention a layer may be prepared from a suitable basic material like a polymer. One side of that basic layer may hâve sealing properties, whereby

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the other side of that layer may be metallised. This means that in the described outer layer the sealing function, the barrier function, and the carrier function are présent in a single layer that is formed out of three sub-layers. This layer is then part of the composite film.

In a preferred embodiment the subject of the présent invention is a sealable molded body for the packaging of oral biologics, particularly oral vaccines formed from at least one composite film, whereby the composite film comprises at least three layers, one of the outer layers is formed as a sealing layer, the other outer layer comprises a nonwoven material and the at least one middle layer is a barrier layer. It is preferred that the composite film is biologically degradable. It is also preferred that adjacent layers arejoined together with an adhesive layer. In that context it is especially preferred that the adhesive layer is in form of a laminating adhesive layer, or in form of an extruding adhesive layer, or in form of a combination of the before named adhesive layers.

It is also preferred according to the invention that the sealing layer, the barrier layer, the adhesive layer and/or the layer of nonwovenmaterial are made of a native biopolymer, comprise a bio-based polymer, a petroleum-based polymer or mixtures thereof. It is especially preferred that the native biopolymer is selected from celluloses, cellulose dérivatives, starches and starch dérivatives; the bio-based polymer is selected from polylactides, polyhy-droxybutyrates, ligninbased thermoplastics, oil-based ethoxyacrylates; and the petroleum-based polymer is selected from -polyesters, polyuréthanes, polyvinyl alcohols, polybutylene adipate terephthalates, polybutylene succinates, polycaprolactones and polyglycolides. In that context it is also preferred according to the invention that the polymer is metallized.

It is especially preferred according to the présent invention that the adhesive is a biologically degradable polyuréthane adhesive.

Preferred is also according to the invention that the barrier layer is biologically degradable and comprises a metallized cellulose dérivative or a cellulose dérivative containing Silicon dioxide and/or aluminum oxide.

It is also preferred that the nonwoven material comprises a fleece or a web that has a fiber length of 1 to 10 cm, preferably 2 to 8 cm, and particularly preferred 4 cm.

Also preferred is that the barrier layer has a blocking effect relative to the fluids: water, air, oxygen, and carbon dioxide.

In a preferred embodiment of the présent invention the sealable molded body is characterized in that the sealing layer has a thickness between 10 and 100 pm, preferably 30 to 70 μm, and particularly preferred 50 pm, the adhesive layer has a thickness between 1 and 10 pm, preferably 2 to 5 pm, and particularly preferred 3 pm, the outer layer of nonwoven material has a thick- ness between 0.1 and 1 mm, preferably 0.2 to 0.5 mm and particularly preferred 0.3 mm and the at least one barrier layer has a thickness between 5 and 50 pm, preferably 10 to 30 pm, and particularly preferred 20 pm.

It is also preferred that the sealable molded body according to the invention is further characterized in that the composite film contains between 1 and 5, preferably 3, and particularly preferred 2 barrier layers.

It is especially preferred that the composite film is thermoformable. The sealable molded body according to invention is preferred in that the composite film has a tensile strength of more than 50 newtons, a tear résistance of more than 10 newtons, a bonding adhesion of more than 1.7 newtons, a permeability of a maximum 10 g/m2/24h water vapor at 38 °C and 90% relative humidity, a permeability of a maximum 3 cm3/m2/24h carbon dioxide at 23 °C and 50% relative humidity and/or a permeability of a maxi- mum 1.5 cm3/m2/24h oxygen at 23 °C and 50% relative humidity.

It is also preferred that the physical properties of the composite film according to the invention should at least be in accordance with MIL-PRF-44073F Performance Spécification for Packaging of Food in Flexible Pouches.

It is also preferred that the composite film is présent in the form of sheet pièces and that the molded body can be produced from two pièces of composite film. In that context it is also preferred that the composite film of the respective pièces is identical or different, at least one composite film being thermodeformable.

Another subject of the présent invention is a method for producing a sealable molded body, wherein a recess is formed in a piece of the composite film by thermal forming in such a way that the outer layer of nonwoven material faces outwardly, the second piece of the composite film according to one of claims 1 to 15 is brought into contact with the first piece of composite film in such a way that the respective sealing layers face one another, and after filling the recess of the molded body, the two pièces of the composite film are sealed together by applying heat to the contact régions.

In another preferred embodiment of the présent invention, the composite film that is the basis of the invention, thus the composite film from which the seal- able molded body can be produced, comprises at least three layers, whereby each of the layers is joined with a laminating adhesive layer, one of the outer layers being formed as a sealing layer, the other outer layer comprising a nonwoven material, and the at least one middle layer being a barrier layer, whereby the composite film is biologically degradable.

A preferred composite film is formed in such a way that the sealing layer has a thickness between 10 and 100 pm, preferably 30 to 70 pm, and particularly preferred 50 pm, the laminating adhesive layer has a thickness between 1 and 10 pm, preferably 2 to 5 pm, and particularly preferred 3 pm, the outer layer of nonwoven material has a thickness between 0.1 and 1 mm, preferably 0.2 to 0.5 mm and particularly preferred 0.3 mm, and the at least one barrier layer has a thickness between 5 and 50 pm, preferably lOto 30 pm, and particularly preferred 20 pm.

In addition, a preferred composite film contains 1 to 5, preferably 3, and particularly preferred 2 barrier layers.

According to the invention, the composite film is formed in such a way that one outer side of the composite film is made sealable. These types of seal- able formations are known to the person skilled in the art. This side of the composite film is directly in contact with the goods to be packaged. In this case, it is provided that the material of the side that is directly in contact with the goods to be packaged is selected in such a way that no interaction occurs with the goods to be packaged. It therefore must be excluded that the packaged goods will be damaged by the packaging or their activity will be adversely affected.

In connection with the présent invention, however, the term sealable is also understood as any configuration of the outside of the composite film that is suitable to be joined with the outside of another composite film. This joining can be effected by adhesion, contact adhesion or bonding of the respective outer sides with one another. In this case corresponding glues or adhesives or adhesion agents known in the State of the art can be used.

In addition, the composite film has a barrier layer. This barrier layer ensures that media from the environment, such as water, water vapor, air, oxygen, carbon dioxide, and other substances présent in the atmosphère do not enter inside the packaging formed from the composite film to reach the packaged goods and damage the packaged goods. On the other hand, the barrier layer ensures that components of the packaged goods, particularly fluids and/or liquids like water, cannot leak out from inside the blister.

According to the invention, it is further essential that the second outer side of the composite film comprises a nonwoven material or a nonwoven material is applied onto the outer side. This nonwoven material represents the surface of the formed packaging that does not corne in contact with the goods to be packaged.

The entire composite film is biologically degradable according to the invention. This property of biological degradability is defined by the standards EN 13432, ASTM D.6400-99 UNI 11183:2006 or AS 4736-2006. The biological degradability is achieved in that the sealing

layer, the barrier layer, the adhesive layer(s) and the layer of nonwoven material comprise a native biopolymer, a bio-based polymer, a petroleum-based polymer or mixtures thereof. Here, it is preferred that the adhesive is a biologically degradable adhesive, for example, a polyuréthane adhesive.

In this case, the native biopolymer is selected from celluloses, cellulose dérivatives, starches and starch dérivatives; the bio-based polymer is selected from polylactides, polyhydroxybutyrates, lignin-based thermoplastics, oil- based ethoxyacrylates; and the petroleum-based polymer is selected from polyesters, polyuréthanes, polyvinyl alcohols, polybutylene adipate terephthalates, polybutylene succinates, polycaprolactones and polyglycolides.

In this context is should be understood that paper or paper libers may also be selected as native biopolymers. Other suitable biologically degradable polymers are known in the prior art, such as those that are described, for example, in DE 196 30 235 Al, DE 198 11 773 Al and DE 198 11 226 Al.

The nonwoven material présent on the outer side of the composite film or forming the outer side of the composite film is also biologically degradable. Appropriate nonwoven materials, for example, are known from DE 44 09 465 A1. The nonwoven material contains at least one degradable polymer/copolymer fiber, or a polymer/copolymer fiber that is degradable by means of contained starches and/or added fermented starches, selected from natural polymers or natural polymers modified with synthetic polymers and/or synthetic polymer libers, which hâve been modified by biological starches, e.g., of potatoes, beets, sugar cane, corn, wheat and the like, in particular those of polyolefins and/or polyesters/copolyesters, which can be obtained, e.g., from starches, fermented starch products or plants modified by strains of bacteria, such as potatoes, rapeseed, etc., also in combination with several, possibly different varieties of biologically degradable polymer fibers and/or natural fibers or copolyamides and/or biological fibers, such as jute, hemp, flax or the like and/or degradable aggregates and/or degradable films. The fleece or the nonwoven material can be configured as hydrophobie or hydrophilic, depending on the respective field of application.

The nonwoven fibers can be produced from a film, e.g., by fibrillating, but may also comprise spun fibers, which, as fleece or nonwoven material, are mechanically reinforced, e.g., by needling or water-jet reinforcement (spun lace method), or are thermally reinforced or are reinforced by binders, or are reinforced by a mixture of ail of these possibilities. In this case, the films and also the spun fibers can be stretched in advance in one or several dimensions. The fleece or the nonwoven material can then be applied onto a layer, for example, by means of an

adhesive. In this case, it is preferred that the nonwoven material comprises a fleece that has a fiber length of 1 to 10 cm, preferably 2 to 8 cm, and particularly preferred 4 cm.

In order to improvethe properties of the composite film, it is provided that at least one of the layers of the composite film is formed as a barrier layer. In addition to the property of biological degradability, which is inhérent due to the polymer itself, aggregates are added to the barrier layer, or métal and/or oxide materials are applied onto the barrier layer in order to provide or to improve the barrier properties. A barrier layer formed from polyvinyl alcohol is known, for example, from DE 196 32 799 Al. Appropriate barrier layers containing métal or oxide materials are known from DE 43 28 767 Al. Particularly suitable in the case of metals are silver, aluminum, iron and the like, while in the case of oxide compounds, the following are particularly suitable: aluminum oxide, cérium oxide, hafnium oxide, magnésium oxide, Silicon dioxide, Silicon monoxide, tantalum oxide, titanium dioxide, titanium (111) oxide, titanium monoxide, yttrium oxide, zirconium oxide, zirconium monoxide and the like, or mixtures thereof. It is particularly preferred that the barrier layer is biologically degradable and comprises a cellulose dérivative, which is metallized or contains Silicon dioxide and/or aluminum oxide.

In order to assure the required use properties of the composite film and the sealable or sealed molded body produced therefrom, it is advantageous that the composite film has a tensile strength of more than 50 newtons, a tear résistance of more than 10 newtons, a bonding adhesion of more than 1:7 newtons, a permeability of a maximum 10 g/m2/24h water vapor at 3 8 °C and 90% relative humidity, a permeability of a maximum 3 cm3/m2/24h carbon dioxide at 23 °C and 50% relative humidity and/or a permeability of a maximum 1.5 cm3/m2/24h oxygen at 23 °C and 50% relative humidity.

It is importantto emphasize in this connection that the barrier properties of the composite film should be effective in both directions. It is important to protect the goods contained in the molded body from environmental influences, thus from influences that act from the outside. However, it must also be ensured that the goods contained in the molded body do not leak out of the molded body.

The described composite film is especially suitable for forming a sealable molded body, which is then provided in sealed form for the oral application of biologics.

Therefore, a subject of the présent invention is also a sealable molded body, which is formed from two sheet pièces of the composite film described here- in. In this case, it is provided according to the invention that the composite film of the individual pièces is identically or differently constructed. This means that the sequence of layers or the number of bander layers can be configured differently in one composite film than in the other composite film. In any case,

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at least one composite film must be configured thermoformable in order to introduce the active substance therein. It may be provided according to the invention, however, to thermally form both pièces of one composite film, whereby one composite film may be identical or different than the other composite film also in this case. It will then be advantageous to thermally form both pièces if larger quantities of active substances are to be introduced.

The production of a sealable molded body according to the invention results in the fact that a recess is formed in one piece of the composite film by thermal forming in such a way that the outer layer of nonwoven material faces the outside, the second piece of the same composite film or a modified composite film is brought into contact with the first piece of the composite film, that the respective sealing layers face each other and after filling the molded body, the two pièces of the composite film are sealed together by application of heat to the contact régions. It is particularly preferred according to the invention that each of the two pièces of the composite film forms a recess by thermo forming.

The production of a sealable molded body according to the invention, how- ever, can also resuit in the circumstance that the composite film from which the molded body is formed does not hâve a sealing layer that can be thermally sealed. In this case, the molded body is first formed by thermoforming, just as described previously, and after this is provided with an adhesive, glue or adhesion layer and only then, optionally after filling the molded body with the goods to be packaged, is closed (sealed), by introducing another composite film. This method variant may be advantageous if the application of heat might lead to an adverse effect on the goods being packaged in the case of the usual sealing layers. The use of an adhesive, glue or adhesion layer may also be limited in this case to the région of the actual contact places.

It is also provided according to the invention to form the molded body in such a way that an excess of material of one of the pièces remains in the région of the sealing seam. For this purpose, for example, pièces with different widths are sealed together. The excess of material projecting from the sealing seam can then be printed on by means of suitable methods. The material excess projecting from the sealing seam is preferably dimensioned in such a way that, along with the printing that may be présent, it also projects out from the entire hait, i.e., the molded body enveloped with the bait material and is visible.

According to the présent invention it is also possible to form the molded body in order to obtain a sachet or a pillow pack or a stick pack. This means that any package form that is known in the art is suitable and in within the scope of the présent invention.

It is also possible and within the scope ofthe présent invention to form amolded v body in form of a sachet or in form of a pillow packs. This means that two composite films are sealed together in order to form a rectangular or square mold that has sealing seam on the four sides of the sachet or pillow.

It is also envisaged according to the invention that the composite film may be molded in form of so-called stick packs as they are currently used for packaging sugar (sugar stick or sugar stick pack). In that case only one composite film is needed and has to be folded or bend along the running direction of the film in order to provide a tube-like mold. This tube-like mold may then be separated into single molds that can be fïlled with the biologie substance or the like and afterwards being sealed and eut into single dosage forms for further processing.

The sealable or sealed molded body according to the invention is suitable in a particular way for the oral application o f biologics.

Agents that are biologically active or effective in veterinary medicine are understood here as biologics, these being produced in classical and/or biotech- nological ways. Included here, in particular, are human pharmaceuticals, veterinary drugs, contraceptives and vaccines in the form of killed vaccines, living vaccines or attenuated living vaccines, produced with classical or bio- technological methods. The active substances prepared correspondingly, in addition to the actual active substances, can also contain additives, excipients and adjuvants that are physiologically tolerable, thus do not act in themselves in a damaging way.

Under the term oral or oral application, in the sense of the invention, is understood the administration of substances by passing a mouth of a human or an animal (per os). Therefore, the substance can be released and/or resorbed in the mouth cavity. Oral biologics in the sense of the invention, however, also comprise préparations that are only released and/or resorbed in the stomach or in the intestinal tract.

The molded body itself is produced from biologically degradable materials. Therefore, the introduction of molded bodies fïlled with active substances into the environment, even in relatively large quantities, is ecologically unobjectionable. Testing for biological degradability can be carried out according to the criteria of relevant standards, such as EN 13432, ASTM D.6400-99 UNI 11183:2006 or AS 4736-2006.

In addition, the molded bodies can be sterilized. Dependingon the active substance to be applied, the préparation and/or the entire filled and sealed molded body must be subjected to sterilization. The sterilization can be conducted by thermal or Chemical methods or by energyrich irradiation. The material of the composite film must be stable relative to the sterilization.

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Due to the barrier layer, the molded body and/or the composite film are/is nearly imperméable to substances acting from the environment, such as water, water vapor, oxygen, carbon dioxide and other substances contained in the atmosphère. The biologics présent in the

molded body are frequently very sensitive and can be damaged and lose their effectiveness due to the action of the named substances. Therefore, the biologics must be protected from these environmental influences.

The composite film is formed in such a way that the polymer layer that cornes into contact with the biologics does not interact with them and, in particular, does not exercise a damaging effect.

The nonwoven material provided on the outer side of the molded body finally fulfills different tasks. The nonwoven material can be configured hydrophobie, hydrophilic, lipophobic or lipophilie, depending on the sélection of the initial materials used. Further, the nonwoven material represents an enlarged effective surface for the molded body. If the molded body is opened or bursts open due to the action of the targeted animal, then the préparation contained therein in liquid or viscous form does not completely run out, but isabsorbedto a considérable e x t en t by the nonwovenmaterial. This means that, in addition, the préparation remains in the région of contact with the targeted animal and thus the probability of oral ingestion of the biologie by the targeted animal is increased. This effect can be reinforcedby the appropriate g ale nie préparation of the biologie, such as increasing the viscosity in the case of liquids.

The nonwovenmaterial, however, can also be suitable for improvingthe adhesion of other materials to the surface by an appropriate configuration of the surface properties. Thus, the molded body can be introduced, for example, into bait, whereby the bait material i s a fat, for example. The surface properties can be correspondingly adjusted or selected also for other bait materials such as proteins, carbohydrates and the like, in order to improve the adhesion. In this way, adhesion of the bait material to the surface of the molded body is reinforced and séparation of the two components of the bait is made diffîcult.

Finally, the use of a sealable molded body according to the présent invention as described herein sealing pharmaceutical substances, especially oral biologics and oral vaccines is another subject of the présent invention.

The invention will now be explained in more detail on the basis of the figures and the embodiment examples introduced therein.

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Figures la and 1b show embodiment examples of composite film 1 according to the invention. In Figure la composite film 1 is shown comprising two outer layers 2 and 3. A composite film 1 comprising two outer layers is the simplest form of a composite film. Composite films in general comprise at least two layers and these two layers are naturally outer layers.

According to the invention, the outer layers 2 must comprise certain properties. One outer layer 2 must hâve at least sealing capabilities. This means that this layer 2 may be sealed with another composite film having an outer layer with sealing capabilities or that the outer layer 2 with sealing capabilities may be sealed with the same outer layer 2 after changing the geometrical arrangement of that outer layer 2 by forming a tube, for example. Beside the sealing capabilities of outer layer 2, outer layer 2 two may also be formed as a barrier layer or a carrier layer. It is also possible and within the scope of the présent invention that these capabilities are inherently combined in one single layer, which then forms outer layer 2.

According to the invention, the other outer layer 3 must also comprise certain properties. As shown in Figure 1 a, the other outer 3 layer has a rough or un- even or microstructured surface. This kind of a surface modification is essential in order to adhéré further material that may be part of a bait. As described herein already, the sealed molded body of the invention is part of a hait that has to be formed around the molded body. This bait is then used to administer the biologics contained in the sealed molded body to an animal. Composite films known in the art do not hâve any uneven or rough or microstructured surface at ail.

In Figure 1b a further embodiment of the présent invention is shown. Outer layer 2 now comprises two sub-layers 4 and 6. Sub-layer 4 is a sealing layer, whereas sub-layer 6 is a barrier or carrier layer. It is possible to form such outer layers 2, comprising two sub-layers 4 and 6 by a co-extrusion process, for example. This means that outer layer 2 now also shows the sealing properties that are entered into outer layer 2 by means of a sealing sub-layer 4.

Outer layer 3 comprises a nonwoven material 7. This is also shown in Figure 1 b.

In order to achieve the adhering properties of the surface of outer layer 3 it is according to the invention also possible to modify the outer layer 3. In that case the outer layer 3 comprises at least a nonwoven material 7, an adhesive material (not shown), a sticky material (not shown) or a combination thereof.

Figures 2a and 2b show further preferred embodiment examples of composite film 1 according to the invention. Composite film I according to the invention, which is shown in Figure 2a, is composed of three layers, each of which is joined to the adjacent layer by a laminating adhesive layer 5. One of the two outer layers is formed as a sealing layer 4. The second outer layer 7 is formed of nonwoven material. A barrier layer”6 is found between these layers.

An example of embodiment of composite film 1 according to the invention, which has 7 more than one barrier layer 6, is shown in Figure 2b. Shown is a composite film 1 having two barrier layers 6, which arejoined together by laminating adhesive layers 5. One of the barrier layers is joined to sealing layer 4 by a laminating adhesive layer 5, and one of barrier layers 6 is joined to the outer layer 7, which comprises nonwoven material, by a laminating adhesive layer 5.

Figure 3 shows an example of embodiment of a sealable molded body 10 according to the invention. Régions of these films, which are also shown en-larged, are characterized in each case by a circle in this figure. Molded body 10 is formed by two sheet pièces of composite film 1 according to the invention. The part of molded body 10, which is shown in the lower région of the figure and which is formed by a piece of film, has a dépréssion or recess, as can be produced by thermoforming composite film 1. A second piece of composite film 1 according to the invention is shown in the upper région of the figure. The two pièces of film of composite film 1 according to the invention are aligned. relative to one another so that each of sealing layers 2 are facing each other. In the enlargements, the schematic structure of composite film 1 is shown, as it is shown also in Figure 2a and within the scope of the description of this figure. As an example, an embodiment o f composite film having one barrier layer 4 is shown. Molded body 10, however, may also be formed by any other embodiment of composite film 1 according to the invention.

Another embodiment of sealable molded body 10 according to the invention is shown in Figures 4a, 4b and 4c. As in the case ofthe example of embodiment of Figure 3, this molded body is also formed by two pièces of film of composite film 1 according to the invention. In Figures 4a and 4b, however, an embodiment is shown, in which both pièces of film hâve been formed prior to sealing. A dépréssion or recess is formed in both pièces of film. Shown is an embodiment in which both parts of sealable molded body 10 are identical. The exemplary structure possessed by the pièces of film of composite filml according to the invention is shown in the enlarged excerpts of Figure 4a.

Figure 4a shows sealable molded body 10, in which the pièces of composite filml according to the invention hâve not as yet been broughtinto contact with one another. The pièces of composite filml are already aligned relative to one another in such away that the molded body can be sealed.

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It is shown in Figure 4b how both pièces of film of composite film 1 according to the invention hâve been brought into contact with one another in order to form the sealable molded body. In practice, when the pièces of film are arranged in this way, the molded body will already hâve been filled and subsequently will be sealed.

Finally, in Figure 4c it is shown, that by rolling in a composite fi 1ml also amold or a sealable molded body 10 may be formed. In this embodiment outer layer 2 faces itself and can be sealed to form a seam-like structure. The resulting tube-like mold can then be separated by additional sealing along the running direction of the tube-like structure (sugar sticks or stick packs). It is also apparent from Figure 4c that the other outer layer 3 now faces outwards and can be used for further adhering of bait material. In order to achieve this nonwoven material 7 (not shown) may be comprised in the outer layer 3.

Figure 5 shows the resuit of a Differential Scanning Calorimetry (DSC) ex-periment performed on composite films according to the invention as laid out in Examples 2 and 3 as described herein.

The following examples explain the présent invention in more detail.

Example 1

General layout of a first embodiment

A molded body according to the invention is formed as follows:

Molded bodies made of composite films, which are sealed with one another, are biologically degradable and thermoformable, provide the following layer structure, from inside to outside:

• Sealing layer of biologically degradable polyester • Biologically degradable two-component adhesive having reactive N-CO group • Barrier layer of biologically degradable, metallized cellulose layer • Biologically degradable two-component adhesive having reactive N-CO group • Attractive-material adhesion layer of biologically degradable nonwoven material made of viscose fibers

Example 2

General layout of a second embodiment

Composite film providing the following layer structure from inside to outside:

• Sealing layer of biologically degradable polyester attached to barrier layer by extrusion laminating process

20096 !fi[ V •--Barrier layer of biologically degradable, metallizcd PVdC layer • Sealing layer of biologically degradable polyester attached to other side of barrier layer | by extrusion laminating process * • Attractive-material adhesion layer of biologically degradable nonwoven material (mixture of viscose and cellulose (l:l/w:w)fibers)

Example 3

General layout of a third embodiment

Composite film providing the following layer structure from insideto outside:

• Sealing layer of biologically degradable polyester attached to barrier layer by extrusion coating process • Barrier layer of biologically degradable, metallized polylactide blend layer (Coex foil) • Sealing layer of biologically degradable polyester attached to otherside of barrier layer by extrusion laminating process • Attractive-material adhesion layer of biologically degradable nonwoven material made of viscose fibers

Example 4

DSC experiments

Figure 5 shows DSC experiments performed with composite films formed according to Examples 2 and 3.

Experiments were performed with a DSC 204 Fl - Differential Scanning Calorimeter (Manufacturer: NETZSCH Gerâtebau GmbH, Germany) at a heating rate of lOK/min in a range from 0 to 300°C under N2. Two heating cycles were performed, interrupted by one cooling cycle in the température range from 300 to -20°C.

As shown in Figure 5, both samples, marked with Ex. 2 and Ex. 3, show a peak in the first heating cycle at about 100 °C. This peak is believed to be associated with the loss of humidity present in the samples. During the cooling cycle both samples show a crystallization peak at nearly the same température. In the second heating cycle both samples also show a crystallite meltingpeak at nearly the same température.

Surprisingly it was found that even if the structure and or the Chemical composition of the composite films are extremely different, the thermal behavior of the composite films

according to the invention are quite similar after the composite has been reconditianed during a first heating cycle.

List of reference numbers

1 Composite film

1^st outer layer

2^nd outer layer

Sealing layer

Laminating adhesive layer

6 Barrier layer I carrier layer

Layer of nonwoven material

Sealable molded body

Conseil en PI

A?

Patent claims

Claims

1. A sealable molded body for the packaging of oral biologics, particularly oral vaccines, formed from at least one composite film, whereby the composite film comprises two outer layers, one of the outer layers is formed as a sealing layer or a barrier layer or a carrier layer, and the other outer layer has a rough or uneven or microstructured surface or comprises at least a nonwoven material, an adhesive material, a stick material or a combination thereof.
2. The sealable molded body according to claim 1, whereby the composite film comprises at least three layers, one of the outer layers is formed as a sealing layer, the other outer layer comprises a nonwoven material and the at least one middle layer is a bander and/or a carrier layer.
3. The sealable molded body according to claim 1 or 2, wherein the composite film is biologically degradable.
4. The sealable molded body according to claims 1, 2 or 3, wherein adjacent layers are joined together with an adhesive layer.
5. The sealable molded body according to claim 4, wherein the adhesive layer is in form of a laminating adhesive layer, or in form of an extruding adhesive layer, or in form of a combination of the before named adhesive layers.
6. The sealable molded body according to one of the preceding claims, further characterized in that the sealing layer, the barrier layer, the adhesive layer, the nonwoven material, the adhesive material, and/or the sticky material are made of a native biopolymer, comprising a bio-based polymer, a petroleum-based polymer or mixtures thereof.
7. The sealable molded body according to claim 6, further characterized in that the native biopolymer is selected from celluloses, cellulose dérivatives, starches and starch dérivatives; the bio-based polymer is selected from polylactides, polyhydroxybutyrates, lignin-based thermoplastics,oil-based ethoxyacrylates; and the petroleum-based polymer is selected from polyesters, polyuréthanes, polyvinyl alcohols, polybutylene adipate terephthalates, polybutylene succinates, polycaprolactones and poly-glycolides.
8. The sealable molded body according to claim 6 or 7, further characterized in that the polymer is metallized.
9. The sealable molded body according to one of the claims 4 to 8, further characterized in that the adhesive is a biologically degradable polyurthane adhesive.

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10. The sealable molded body according to one of the preceding claims further characterized in that the barrier layer is biologically degradable and comprises a metallized cellulose dérivative or a cellulose dérivative containing Silicon dioxide and/or aluminum oxide.
11. The sealable molded body according to one of the preceding claims, further characterized in that the nonwoven material comprises a fleece that has an average fiber length of 1 to 10 cm, preferably 2 to 8 cm, and particularly preferred 4 cm.
12. The sealable molded body according to one of the preceding claims, further characterized in that the barrier layer has a blocking/efféct relative to the fluids, namely water, air, oxygen, and carbon dioxide. )
13. The sealable molded body according to one of the preceding claims, further characterized in that the sealing layer has an average thickness between 10 and 100 pm, preferably 30 to 70 pm, and particularly preferred 50 pm, the adhesive layer has a thickness between 1 and 10 pm, preferably 2 to 5 pm, and particularly preferred 3 pm, the outer layer of nonwoven material has a thickness between 0.1 and 1 mm, preferably 0.2 to 0.5 mm and particularly preferred 0.3 mm and the at least one barrier layer has a thickness between 5 and 50 pm, preferably lOto 30 pm, and particularly preferred 20 pm.
14. The sealable molded body according to one of the preceding claims, fùrther characterized in that the composite film contains betweenl and 5, preferably 3, and particularly preferred 2 barrier layers. —
15. The sealable molded body according to one of the preceding claims further characterized in that the composite film is thermoformable.
16. The sealable molded body according to one of the preceding claims, further characterized in that the composite film has a tensile strength of more than 50 newtons, a tear résistance of more than 10 newtons, a bonding adhesion of more than 1.7 newtons, a permeability of a maxi- mum 10 g/m2/24h water vapor at 38 °C and 90% relative humidity, a permeability of a maximum 3 cm3/m2/24h carbon dioxide at 23 °C and 50% relative humidity and/or a permeability of a maximum 1.5 cm3/m2/24h oxygen at 23 °C and 50% relative humidity.
17. The sealable molded body according to one of the preceding claims, further characterized in that the composite film is présent in the form of sheet pièces and that the molded body can be produced from two pièces of composite film.
18. The sealable molded body according to claim 17, further characterized in that the composite film of the respective pièces is identical or different, at least one composite film being thermodeformable.

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19. A method for producing a sealable molded body according to claim 17, wherein a recess is formed in a piece of the composite film by thermal forming in such a way that the outer layer of nonwoven material faces outwardly, the second piece of the composite film according to one of claims 1 to 16 is brought into contact with the first piece of composite film in such a way that the respective sealing layers face one another, and after filling the recess of the molded body, the two pièces of the composite film are sealed together by applying heat to the contact régions.
20. Use of a sealable molded body according to any of the claims 1 to 18 for sealing pharmaceutical substances, especially oral biologics and oral vaccines.