Untitled record

This invention relates to polyvinyl chloride multilayer tubes for medical purposes, in accordance with paragraph 1 of the claims, to a method for the production of such polyvinyl chloride multilayer tubes, in accordance with paragraph 18 of the claims, as well as to the use of such multilayer films.

<td colspan="2">The known level is described in the documents listed below.</td>

<td>WO-A-92/11820</td><td> (1),</td>

<td>DE-A-28 31 034</td><td> (2),</td>

<td>US-A-4,948,643</td><td> (3),</td>

<td>EP-A-0 136 848</td><td> (4),</td>

<td>DE-PS-44 04 041</td><td> (5),</td>

<td>DE-OS-42 19 071</td><td> (6),</td>

<td>DE-OS-39 14 998</td><td>(7) and</td>

<td>WO-A-93/23093</td><td> (8).</td>

For example, the polyvinyl chloride materials described in (1) are known and their single-layer tubes having only one layer. This document proposes a tube material for medical purposes, consisting of a mixture of polyurethane and polyester, which can be sterilized by autoclaving, as well as thermo-gluing, gluing and fusing with the high-frequency method. The described tube material does not contain bis (2-ethylhexyl) phthalate plasticizer, polyvinyl chloride and phthalate, which has carcinogenic properties. However, as a plasticizer, this material additionally contains a certain amount of citric acid ester (butyryl trihexyl citrate) and other technological auxiliary substances, for example, internal or external lubricants. Although the thermoplastic plastic described in (1) can be processed by known shaping methods - extrusion, blow molding or injection molding, it is mainly intended for use as a material for medical bags or for connectors made of polyvinyl chloride. And only with these conventional polyvinyl chloride materials does it show satisfactory compatibility, in particular, it can be subjected to thermo- or high-frequency bonding.

In (2), polyvinyl chloride plastic compositions are described which are suitable for the manufacture of tubes for pumping blood or medical solutions. In particular, plastic compositions are provided containing from 10 to 40 weight. % polyolefin, mainly consisting of propylene units, from 40 to 85 weight. % block copolymer obtained from elementary units of polyethylene or polybutylene as a central block and polystyrene as edge blocks, from 10 to 40 weight. % polymer plasticizer based on polyethylene and, optionally, an antioxidant. Although the described materials have flexibility, extreme heat resistance, required softness and can be used for medical purposes, as well as a very high ability to solve the aging problems caused by plasticizers with low molecular weight, their strength and rigidity leave much to be desired. Any increase in the rigidity of this single-layer material due to an increase in the proportion of propylene will lead, in particular, to a decrease in the rigidity and flexibility of the finished product — a tube or bag.

In (3), multilayer tubes for medical pipelines are presented. Three-layer tubes are described, the outer layer of which is made on the basis of ethylene vinyl acetate (EVA), and the inner layer is made of polyvinyl chloride (PVC). Due to insufficient adhesion between the inner and outer layers, a binder layer consisting of vinyl acetate and acrylates is coextruded with two other materials as a central layer. Plastics with the above-described layer structure, in particular, are suitable for use as connecting elements, connectors, or tubes for medical bags made of EVA (ensures compatibility of the outer layer with the bag) and allow the insertion of a PVC membrane tube and securely fasten it to the connecting element or in a tube by, for example, bonding with a solvent.

From the medical point of view, the multilayer tubes described in (2) have a number of drawbacks due to the fact that the PVC layer contains a significant amount of trimellitic acid esters as plasticizers, which can be carcinogenic.

In (4), multilayer tubes are described that can be considered as a potential replacement for PVC tubes for medical applications. However, the use of PVC is not completely excluded in them; in fact, they require its use as a component of the material or mixture for the intermediate or inner layer.

In particular, in (4) three-layer tubes for medical purposes are considered. The inner layer of these tubes consists of a copolymer of ethylene and propylene, polypropylene, a polyether copolyester and polyethylene terephthalate, polyurethane, polyvinyl chloride or a mixture of a copolyester and a copolymer of ethylene and vinyl acetate.

The intermediate layer may consist of linear low density polyethylene (LLDPE), a copolymer of ethylene and vinyl acetate (EVAS), a modified EVAS, a copolymer of ethylene and methyl acrylate (EMAS), a modified EMAS, PVC, or a mixture of the above.

The outer layer is formed of polypropylene, a copolymer of ethylene and propylene, or a modified copolymer of ethylene and propylene.

The choice of these materials for the intermediate layer is mainly determined by the ability of these materials to give the necessary flexibility to the finished structure of the multilayer tube. The selection criterion for the material of the inner layer is heat resistance, sufficient so that the resulting tube can be autoclaved, and the choice of material of the outer layer is mainly determined by the need to provide relatively stable ultrasonic, thermal or high-frequency bonding with a polycarbonate connector.

In addition to the fact that the use of PVC is not completely excluded in the tubes described in (4) and they provide compatibility with polycarbonate, they are even less suitable for bonding with other new and highly advantageous materials based on polypropylene for bags or connectors.

Moreover, the flexible central layer described in (4) is usually the thickest layer, which often causes inadequate stiffness of the finished tube. Thus, usually, and not only additionally, the extruded tubes must be irradiated in order to be able to carry out high-temperature sterilization due to radiation crosslinking. And this is a rather complicated operation.

In (5), a polymer material for medical devices was described. Describes very low density silane grafted polyethylene (VLDPE) or ultra low density polyethylene (VLDPE), which were structured with subsequent use of moisture to obtain, for example, transparent, bend-resistant and sterilizable tubes, in particular by extrusion.

A necessary condition for the possibility of steam sterilization of the finished product is a high temperature structuring. Although the material is an obvious replacement for PVC, the resulting single-layer tubes are not able to form a good and direct connection with the insert during simple high-temperature sterilization without violating dimensional stability.

The document (6) describes disposable radiation-sterilizable infusion and transfusion sets in which all components are made of thermoplastic or elastoplastic homopolymers, copolymers or block copolymers based on polyolefins.

In particular, connecting tubes made of LLDPE or linear PEONP are presented in (6), but the use of EVA or special ionomers is not ruled out.

These tubes are connected by the use of organic solvents such as cyclohexane. They can also be thermally fused with ultrasound or glued with adhesives hardening under the influence of light or ultraviolet radiation.

Document (7) relates to blood infusion or transfusion systems. In order to ensure proper disposal, all components of these systems are made of one polymer, copolymer or block copolymer without the use of PVC. The polymeric materials used are based on styrene polymers.

Document (8) relates to polyvinyl chloride coextruded multilayer tubes for medical purposes, the main layer of which consists of a mixture of polyamide and EVA. An outer layer is applied to this inner base layer using a bonding layer.

The binder layer mainly consists of a copolyester and an SEBS copolymer, possibly PP and EVA. The choice of materials suggests that the described tube has disadvantages caused by the use of EVA, copolyester or polyamide.

In light of the fact that the above implementations are imperfect, the object of the present invention is to provide such a tube for medical purposes, which can be compatible with various materials of connectors and bags, in particular based on polypropylene or polycarbonate. The objective of the invention is also to achieve a strong connection with new tube materials without the use of additional binders or the like. In addition, the new multilayer tube should be sufficiently flexible, flexible and soft and, at the same time, as much as possible, resistant to kinks, relatively dimensionally stable and thermostable. Finally, in contact with solutions commonly used in medicine, the tube should also not release any harmful substances into these fluids and, in particular, should be inert with respect to medical solutions. An object of the present invention is also a method for producing such a multilayer tube.

These and other objectives, not set forth in detail, are achieved by means of a non-vinyl chloride multilayer tube for medical purposes, the features of which are described in the characterizing part of claim 1. Particular developments are given in the paragraphs dependent on paragraph 1 of the claims. The method according to the invention is described in paragraph 18, and paragraphs. 26 and 27 protect the use of a polyvinyl chloride multilayer tube in accordance with the invention.

Such a polyvinyl chloride multilayer tube for medical purposes consists of at least two layers, of which the main layer A of the first plastic is bonded to at least one connecting layer B of the second plastic. Moreover, the first plastic contains at least one polymer that without deformation can withstand high-temperature sterilization at a temperature greater than or equal to 121 ° C, has a Shore D hardness index of less than or equal to 32 and a residual stress at a temperature of greater than or equal to 121 ° C, sufficient to obtain a press fit at the connection point, and from it it is possible to make a ring or loop with a diameter of up to 60 mm without bending, and the second plastic contains at least one polymer, which during high-temperature sterilization at 121 ° C shows a tendency to stretch under the influence of the pressing force arising from the press fit, and which has a Shore A hardness index of less than or equal to 65, while the first plastic is dimensionally stable at temperatures greater than or equal to 121 ° C, and the second plastic at this temperature is not dimensionally stable. This allows you to get a flexible tube, which is transparent at the end of high-temperature sterilization, has sufficient bending strength and can be pinched by pipe clamps or the like. In addition, the polyvinyl chloride tube according to this invention further has the ability to provide a tight seal to the medical bag or connector extremely simply during possible high-temperature sterilization.

This invention is based, among others, on the concept of adapting layers of various plastics to each other in a multilayer tube material in such a way that at least one layer acting as the main layer gives the tube material sufficient thermal stability, and at least , another layer acting as a connecting or binder, provides the formation of a durable and tight connection with the bag, the input, connector or other tube without the need to resort to the use of additional adhesives, sealants, or sealing compositions, or auxiliary substances, or other bonding methods (high-frequency method, etc.)

In the context of this invention, the term sterilization is used to refer to the process of killing or inactivating (viruses) of all microorganisms, including very resistant forms at rest, when the tubes must, in particular, withstand sterilization in autoclaves with high pressure steam at at least 121 ° C, which corresponds to a pressure of approximately one atmosphere above atmospheric, the so-called autoclaving, or autoclaving, without any violations.

In the context of the present invention, the term plastic is used to mean materials mainly consisting of macromolecular organic compounds, where plastics are also known as polymers, in particular including homopolymers and copolymers (statistical, block and / or grafted polymers) and mixtures of the above.

Dimensional stability during high-temperature sterilization is one of the main criteria for the selection and introduction of a polymer into a plastic and, therefore, into a specific functional layer of a multilayer PVC-free tube for medical purposes.

In this regard, plastic is considered dimensionally stable if the tube sample with a length of at least 10 mm, an inner diameter of 5 mm and an outer diameter of 7 mm withstands sterilization with 121 ° C hot steam when heated for at least 15 minutes, held for at least 15 minutes and cooled at least 10 minutes, without visible changes, such as flattening or ovality.

The temperature, in the sense of the softening temperature of polymers or plastics, according to this invention is the temperature of steam sterilization, namely 121 ° C. Since the main layer contains a polymer having dimensional stability and, thus, thermal resistance to deformation even at temperatures above 121 ° C, the possibility of free-flowing softening of the main layer or its liquid state during steam sterilization is largely excluded, in while the polymer is the plastic of the connecting layer, reaching a state of free-flowing softening at compression pressure at 121 ° C, allows to achieve softening of the connecting layer under standard conditions of steam sterilization. Therefore, a connection can be formed at the point of contact with the connected element without uncontrolled change in the shape of the tube.

The indicated temperatures in each case relate to the pressure during steam sterilization, i.e. approximately 1 atmosphere above atmospheric. However, it should be understood that the dependence of the softening temperature on the pressure in the range from standard pressure to above atmospheric pressure required for steam sterilization is generally negligible.

Depending on the desired function of the polyvinyl chloride tube of the present invention, it may be effective to place a special layer B capable of forming a compound on the external, internal, or both external and internal sides. The polyvinyl chloride multilayer tube of the present invention is also preferably characterized by the sequence of layers BA, AB or BAB, in each case counting from the inside out.

In the first case, the tube of this invention, for example, can be worn on a connector of a suitable material so that the inner layer of the tube is in contact with the outer surface of the connector. In the second case, the tube according to this invention is intended to be placed in a hollow object, the inner surface of which is made of a material suitable for forming a connection. According to the present invention, both connection methods are possible alternatively or simultaneously when there are two connecting layers (external and internal) in the polyvinyl chloride multilayer tube. For connecting to the connector, the connecting layer is preferred inside, and for connecting with, for example, a bag, the connecting layer is preferred on the outside.

In addition to the above-described base and connecting layers, in a preferred embodiment of the present invention, the polyvinyl chloride multilayer tube also has a functional layer, namely at least one additional transparent peripheral layer C of a third plastic. This layer C can be either external or internal.

The peripheral layer provides the multilayer tube with improved surface properties and qualities in the sense of stickiness, dullness, low friction coefficient, transparency and adhesion characteristics.

In principle, layer C can act as a final layer either internally or externally. However, according to the present invention, it is preferable that in the case where the bonding layer B is an outer or inner peripheral layer, the corresponding opposite peripheral layer is layer C.

In the most advantageous development, at least the additional peripheral layer C is designed to form a tube with jaws (Fig. 2). Accordingly, implementations of polyvinyl chloride multilayer tubes highly preferred in accordance with this invention are those characterized by a sequence of layers of BAC / CAB / CBAB or BABC, in each case counting from the inside out. The inner layer must be compatible with the solution flowing through the tube.

In order to provide the aforementioned characteristics of the layer C, in a further advantageous implementation, the coating layer C consists of a third plastic material which contains at least one polymer with a thermal deformation resistance temperature greater than 121 ° C.

In the preferred polyvinyl chloride tubes of this invention, the first plastic for the base layer predominantly contains synthetic isoprene rubber or propylene with a density of 0.9 g / cm3, and the second plastic for the connecting layer predominantly contains a polyethylene copolymer or synthetic rubber with an Mw of 100,000 g / mol. This combination for each base layer A and the bonding layer or layers B provides many of the required characteristics. The following polymers are mainly used to solve the problems of the present invention. Percentages are given in weight percentage units.

Cover layer: Thickness 10-50 microns;

% - 60% of SSPPP (PP23M 10 cs 264, REXENE) and% - 40% of SIS (HVS 3, Kuraray); or Tuftec H 1052 (Asahi).

Main layer: Thickness 900-980 microns with a tube wall thickness of approximately 1 mm;

50-100% ICU (HVS / 3, Kuraray) and

50-0% SSPPP (PP 23 March, 1996 10 cs 264, REXENE); - polypropylene: Shore hardness index D &lt;32, ρ = 0.9 g / cm3; (e.g. Adflex 100 G, Himont, rubber content up to 50%, e.g. PIB, styrene / ethylene / butyl rubber, styrene / ethylene / propylene rubber, ICU).

Connecting layer: Thickness 10-50 microns;

one hundred % SEBS (PR 3415, Wittenburg)

one hundred % SEPS (Septon 2277, Kuraray) or

50-100% PE copolymer (Engage XU58.000 52, DOW) and

0-50% SEBS / SEB (Kraton G 1726, Shell);

Accepted abbreviations:

PIB - polyisobutylene

SSPPP - statistical polypropylene copolymer

SIS - styrene / isoprene / styrene

SEBS - styrene / ethylene / butylene / styrene rubber

SEB - styrene / ethylene / butyl rubber

SEPS - styrene / ethylene / propylene / styrene rubber.

Regarding the adhesion between the layers of materials A, B and C, it can be argued that this figure is in principle normal. Adhesion, however, can be improved due to the fact that each of the layers A, B and / or C of polyvinyl chloride multilayer tubes will additionally contain up to 40 weight in the plastic of which it is made. % relative to 100 weight. % of the composition, as described and defined above, of the plastic of which one or both adjacent layers are made. Another intermediate layer of polymeric materials of adjacent layers also leads to a positive result.

Such a mediator or material replacement significantly increases the overall compatibility of the layers of which the tube is formed, without compromising other characteristics.

Another significant and preferred feature of the invention is that for a polyvinyl chloride multilayer tube, plastics for all layers are selected in such a way that they mainly consist of homopolymers of polyolefin or copolymers of polyolefin, or from their modification (for example, SEBS). It was especially surprising that this invention for the first time makes it possible to create a non-vinyl chloride multilayer tube consisting solely of materials that meet the requirements of environmental protection, while at the same time allowing directly to form connections with connectors during steam sterilization and at the same time fulfill all the requirements for tubes for medical applications.

As for the geometric shapes, the tubes can be produced in any required and standard thickness and size. The polyvinyl chloride multilayer tube of the present invention preferably consists of more than 96-98 weight. %, relative to the total volume of the tube material, the base layer A. The individual layers themselves preferably have the following thickness indicators: the base layer A is more than 900 μm, the connecting layer B 10-50 μm and the connecting layer 10-50 μm.

The present invention also provides a method of manufacturing a polyvinyl chloride multilayer tube for medical purposes, from a plastic multilayer film consisting of at least two layers, in which the first plastic to form the base layer A and the second plastic to form at least one connecting layer glued to the first, coextruded at the same time and form essentially a coaxial and cylindrical multilayer tube. This method is characterized in that the first plastic is used, which withstands high temperature sterilization without deformation at a temperature greater than or equal to 121 ° C, has a Shore D hardness index of less than or equal to 32, and a residual stress at a temperature of greater than or equal to 121 ° C, sufficient to obtain a press fit at the connection point, and from which it is possible to form a ring or loop with a diameter of up to 60 mm without bending, and the second plastic used contains at least one polymer which, during high-temperature sterilization at 121 ° C, tends to stretch under the action of the pressing force arising from a press fit, and which has a Shore A hardness index of less than or equal to 65, while the first plastic is dimensionally stable at temperatures greater than or equal to 121 ° C, and the second plastic is not dimensionally stable at this temperature.

Forming is carried out by methods known to specialists in this field, for example, by a vacuum method. A particularly important feature of this invention is the ability to coextrude at the same time two or more layers in order to combine in the tube two or more desired properties of various components to improve its quality.

At the same time, coextruding allows, with the appropriate selection of extruders, the production of custom non-vinyl chloride multilayer tubes, completely avoiding the use of binders and, nevertheless, controlling the receipt of the required characteristics and other additional important characteristics of the tube, such as gas and water permeability, strength, fusibility, transparency and heat resistance.

The selection of co-extruded layer materials is extremely important. The plastics or layers are preferably selected such that all layers of the non-vinyl chloride multilayer tube mainly consist of homopolymers of a polyolefin and / or copolymers of a polyolefin, or of polymers based on them such as, for example, modifications of polyolefins (e.g. SEBS).

Although coextruding such materials is known in principle, based on today's experience it was impossible to predict the possibility of direct production of multilayer tubes of such complexity as according to this invention. The fact that this was possible in the framework of this invention was completely unexpected, because in practice, on the contrary, it was often found that even based on the properties of polymers sometimes given in tables, for example, information on composite adhesion, the result was not always successful. This means that achieving this goal by simply selecting materials from the known ones is not possible for multilayer coextruded tubes. It is especially difficult to control the degree of melt viscosity when coextruding rubbers such as polyisobutylene (PIB) with polypropylene (PP).

Even more preferred in the method according to this invention is that to obtain a polyvinyl chloride multilayer tube, plastics are selected so that all layers of the tube additionally contain up to 40 weight. % material adjacent layer or layers. Thus, to a certain extent, it becomes possible to correct low adhesion between two adjacent layers. Upon completion of the shaping process itself, the resulting tube can then be processed using conventional methods.

Water quenching of the tube after shaping is preferred. Such quenching freezes the amorphous state to obtain the optimal composite property, increased flexibility and adequate rigidity, but, in addition, quenching of the melt increases the transparency of the tube, because does not allow crystallization zones to form. This leads to a small degree of crystallinity, and, as a consequence, to increased transparency and strength.

The polyvinyl chloride multilayer tubes of this invention are extremely suitable for use in medicine. All materials of the multilayer tube are selected so that the tube is transparent, flexible and flexible, at the same time it can undergo high-temperature sterilization and, due to the fact that it has the ability to exert a compressive force, form a strong, bacterium-resistant connection with the connector. Moreover, the polyvinyl chloride multilayer film of the present invention is also biocompatible. It was possible to avoid the use of PVC, which always contains some plasticizers, as well as binders that can diffuse through the layers of plastic.

Owing to their excellent characteristics and properties, the polyvinyl chloride multilayer tubes of this invention are particularly preferred as pipelines for supplying liquids during dialysis, infusion or artificial feeding. For this, it is convenient to have a sponge for connection to the supply volume, at least in the connection area.

The compatibility of the material of the connecting layer of the multilayer tube according to this invention with the taps of medical bags (mainly made of polypropylene) and / or the elements commonly used in medicine for connecting to, for example, connectors made of polypropylene, is a particular advantage. The connectors or pouches may have a rough surface with which the polyvinyl chloride multilayer tube of the present invention is mated in such a way that the inner surface of the polyvinyl chloride multilayer tube with the connecting layer B forms a press fit on the rough external surface of the connector or pouch (or bag input).

The formation of a good and reliable connection is ensured due to the surface properties of the parts made of polypropylene and the fluidity of the connecting layer B of the tube under the influence of heating, for example, during steam sterilization, since the material of the connecting layer flows into the roughness of the surface of the connector or the input of the bag. The bond is further improved if the plastics used in the manufacture of the tie layer B of the tube are mixed with 1-40 weight. %, relative to 100 weight. % of the material of the connecting layer, the plastic of which the connectors or bag entry are made. The joint can be improved by roughening the surface. Other advantages and features of the invention can be clarified using examples that are demonstrated with reference to the accompanying drawings.

The figures show:

FIG. 1 is a sectional view of a tube made of a polyvinyl chloride multilayer film according to this invention;

FIG. 2 is a cross-section of a tube with jaws made in accordance with this invention. The figures show a three-layer tube 1 according to this invention. On the example of the invention shown in Fig. 1, in tube 1, outer layer 2 is a peripheral layer C of a mixture of SEBS, SEPS, PP and SIS or a mixture of PP / styrene / ethylene / butylene / (propylene) rubber, SEBS and / or SEPS.

The main layer A is layer 3, which makes up the largest fraction of the volume of the tube wall. Suitable materials, among others, are styrene / ethylene / butylene rubber with PP, polyisoprene (PIP) with PP, SEPS with PP, PP and SIS with PP.

The connecting layer 4 consists of SEBS with SEBS / SEB (Kraton G 1726 and Kraton G 1652, Shell) and a copolymer of PE (Engage XU58000, 52 DOW) with SEBS / SEB (Kraton G 1726, Shell), SEPS / SEP (Septon 2277, Kuraray). Here, SEBS (Kraton G 1726) is SEBS with a low molecular weight and containing at least 20% diblocks, while SEBS (Kraton G 1652) is SEBS with a high molecular weight and not containing significant amounts of diblocks.

Values ​​of dimensional stability, elastic modulus and hardness of layers A, B and C are shown in the table.

<td></td><td>Elastic modulus</td><td>Shore Hardness</td><td>Heat softening point</td>

<td>Base layer A</td><td>&lt;80 N / mm²</td><td>D &lt;32</td><td>&gt; 121 ° C</td>

<td>Connecting layer</td><td>&lt;80 N / mm²</td><td>A &lt;65</td><td>&lt;121 ° C</td>

<td>Peripheral layer</td><td>&lt;1000 N / mm² ,</td><td>&lt;R90 *</td><td>&gt; 121 ° C</td>

- Rockwell hardness, cf. DIN 10109-1.

Other advantages and implementations may be understood from the following claims.

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FIG. 2

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