DE19517754C1 - Biocompatible porous hollow polyolefin fibres used as exchange materials and semipermeable membranes - Google Patents

Abstract

Biocompatible, porous hollow fibres of polyolefin material having a coating of biocompatible carbonaceous material, formed by (i) introducing the preformed porous hollow fibres into a gas phase of monomeric vinylidene chloride (1,1-dichloroethylene); (ii) inducing a graft polymerisation reaction and grafting a uniform layer of polyvinylidene chloride onto the hollow fibres; and (iii) splitting off HCl in a dehydro:chlorination reaction to a residual Cl content of <= 6% based on the Cl content of the original polyvinylidene chloride layer.

Description

The invention relates to a porous hollow thread, the one Coating made of a biocompatible carbon material having. The invention further relates to a method for Production of such hollow threads. Furthermore, he concerns selected applications of these biocompatible, porous hollow threads.

Microporous, open-cell hollow fibers are known in the professional world knows. A particularly important application concerns the one set as an exchange medium for gas exchange, for example in Oxyge generators, for filtration, ultrafiltration and microfiltra tion, for example in blood filters, for dialysis, for the reverse Osmosis, for heat exchange and the like. The extent of the bottom Rosity and the dimensions of the pores are relevant to these applications adaptations; typically the porosity can be 10 to 50%, and the pores have dimensions less than 1 micron. In these applications, the thread wall typically comes in Contact with blood and / or plasma. Frequently used company The materials are polyester, polyethylene and in particular Polypropylene.  

There are essentially two different methods of making them position of microporous, open-cell hollow fibers made of Polypro pylen became known. According to an alternative stretched hollow threads at a temperature below 110 ° C considerably stretched. This stretching creates porous areas perpendicular to the stretching direction; compare DE-PS 26 30 374. Another proposal of this type follows in addition to the cold drawing, a hot drawing; compare DE-OS 30 03 400. According to another alternative becomes a homogeneous, single-phase mixture of two components ten, namely a thread-forming polymer such as Polypro pylene, and from another inert to the polymer Liquid, extruded into a bath, the hollow thread formed solidified structure and then with a solvent treated to remove the liquid component. To This alternative creates the pores and micropores Removing and removing the second component; compare DE-PS 28 33 493. According to a modified embodiment the latter method can also be microporous Hollow filaments obtained from polyethylene; compare DE-PS 27 18 155.

In this context, "biocompatibility" describes the Interactions of the polymeric thread material with blood and / or plasma. In contact with such "foreign" surfaces hemolysis may occur, reducing the number the erythrocytes, with the consequence of a decreased acid uptake of substances in the blood. Therefore a higher oxygen Partial pressure can be provided in the extracorporeal system, which in turn promotes hemolysis. You can also join accumulate leukocytes on the surface of the thread, which increase after surgery lead to a decrease in the required number of leukocytes, and thus cause a higher susceptibility to infection. Furthermore, the thread surface can also be activated  of the complement complex lead with appropriate effects effects on the immune system and blood factors. Finally the thread surface can activate the coagulation cascade to the formation and attachment of fibrin clots and Thrombi. The thread surface should have the highest possible bio have compatibility to activate the above inhibit or completely prevent the aforementioned processes. Ins in particular, the thread surface is said to have a high hemocompatibility lity and a low tendency to form thrombi (anti Thrombogenicity).

Among the materials currently available is pyrolyti shear carbon one of the materials with the best bio compatible properties. Typically, the Py requires Rolysis of carbonaceous raw material and waste formation of the pyrolytic carbon thus formed on a Substrate high temperatures of 800 to 1000 ° C and more. In plantable products of this type and processes for their manufacture position are e.g. in the U.S. Patent specifications 4,164,045 or 3,925,334 or 3,526,005 or 3,685,059 or be in British Patent 12 26 833 wrote. Most substrate materials, especially on the base of organic plastics are such high Damaged temperatures. The European patent specification EP 0 224 080 B1 and the U.S. Patent 5,370,684 open a process for the production of a prosthetic device tion, which is a support layer from an organic art fabric ("DACRON", "TEFLON") and a coating of one has biocompatible carbon material. As a "prosthesis device "also includes a" DACRON "thread, for example Form of surgical sutures. The Be stratification occurs at comparatively low temperatures by sputtering a carbon target at voltage and current generated and separated. The fat the coating thus produced is less than 1.0 µm. This carbon material is said to be a microcrystalline  Lines have structures with a turbostratic structure. The The process is complex, and its productivity ver equally low. In the event of improper contact the extraordinarily thin carbon layer is slightly removed rub.

Oxygenators, blood filters, dialyzers, and the like directions are mostly designed for single use. In such devices, more than 1 m² of exchanger is often used surface provided on the basis of hollow threads. Porous Hollow threads of this type are therefore used to a considerable extent compelled. For coating large quantities of hollow fibers pyrolytic carbon is the one cited above Low temperature sputtering process too expensive.

Furthermore, in British patents 856,329 or 801,531 have proposed the properties poly merer substrates by changing on their surfaces a coating is grafted on. This grafted on Polymer layer is made with the help of radical polymerization generated from ethylenically unsaturated monomers. The radika Polymerization can be caused by ionizing radiation be reduced. Typically it is considered to be ethylenically unsaturated used monomer methyl acrylate used. To a large extent Enumerating other suitable monomers will also be sufficient Called vinylidene chloride. With the help of this grafted on Coating is said to have a variety of different properties ten can be achieved or improved, but the Erzeu coating with biocompatible properties not addressed.

In addition, in World Patent Index, unit numbers 087819 D / 06 and 69927 A / 39 the grafting of vinylidene chloride on polyolefin substrates.

In contrast, this is the basis of the present invention technical problem lies in a porous hollow thread to provide the type described above, the one chemically bonded coating made of biocompatible carbon  has material. Furthermore, the present Invention a method can be given to such bio compatible hollow threads under comparatively simple procedure conditions in high productivity and more consistent To provide quality. In particular, the Erfin such a method can be specified that a Be supplies layers of biocompatible carbon material, the excellent tolerance to blood and a has high thromboresistance.

The porous and biocompatible hollow fiber according to the invention has a porous hollow fiber structure made of a polyolefin material and a coating of a biocompatible Koh lenstoffmaterial on. The peculiarity is that this coating is available through

• - Introducing a pre-formed porous hollow thread in a gas phase from monomeric vinylidene chloride (1,1-Di chlorethylene);
• - inducing a graft polymerization reaction and Grafting a uniform layer of poly vinylidene chloride on the hollow thread; and
• - Subsequent elimination and removal of chlorine hydrogen (dehydrochlorination) until a residual Chlorine content less than 6%, based on the chlorine content the original polyvinylidene chloride layer.

A coating produced in this way typically has one Layer thickness greater than 5 microns is chemically related to that Thread material bound and consists essentially of a pure carbon material, the excellent biocompatible Has properties. The gas phase graft polymerization and the subsequent dehydrochlorination can be under perform such conditions that the mechanical Do not impair the properties of the thread material. Also the porosity of the thread structure remains essentially the same  hold. The coating is flexible and insoluble with the Thread connected. The coating can practically with larger, adjustable layer thickness can be generated. Limited kungen result from a decrease in the original original porosity by grafting on the polyvinylidene chloride layer.

Another important aspect of the invention relates to a Process for making this porous, biocompatible Hollow thread. The method according to the invention is characterized net through the following process steps:

• - A preformed, porous, from a polyolefin mate rial existing hollow thread is sealed in a tight closable vessel introduced;
• - The vessel is filled with monomeric gaseous vinylidene charged with chloride;
• - A graft polymerization is carried out inside the vessel. Reaction induces an even polyvinyli grafting the layer on the thread material;
• - The whole or in part with a coating Hollow thread provided with polyvinylidene chloride becomes reak exposure conditions that lead to a spin-off and removal of hydrogen chloride (dehydrochloria lead);
• - This dehydrochlorination will last at least as long carried out until the residual chlorine content of the coating tion is less than 6%, based on the chlorine content of the original polyvinylidene chloride Layer.

Another important aspect of the invention relates to the use of these special hollow threads or hollow fibers as a semipermeable membrane in oxygenators, dialysis machines, Hemoconcentrators, blood filters, blood defoamers, dialysis  filter and other filter devices as well as others Extracorporeal circulation devices.

Advantageous refinements and developments of the Erfin result from the subclaims.

To produce the biocompatible hollow fibers according to the invention can of conventional, commercially available porous Hollow threads are assumed. The thread material is typical usually a polyolefin material. As suitable polyolefins come especially polyethylene and polypropylene and gelebe if necessary, further higher α-olefins into consideration, poly propylene is particularly preferred. Under the label "Polypropylene material" is said to be all in medicine and biology usable polypropylene plastics are understood finally polypropylene copolymers with other α-olefins, Polypropylene homopolymers and polypropylene blends. Next Such modified polypropylene materials are also out suitable, the molecular weight reduced and in certain ten limits has been set to certain mechanical To achieve properties. Such a targeted breakdown of the Molecular weight can be known by radical Ab construction with peroxide or the like.

Other plastics commonly used in medicine are less suitable. Polytetrafluoroethylene (TEFLON) would those for inducing radical polymerization γ radiation which is preferably used can be destroyed. Poly esters, such as DACRON, would be affected by the reaction conditions be hydrolyzed, which are intended for dehydrochlorination are.

Porous hollow threads serve as the starting material porosity adapted to the application. Typi The porosity is said to be a gas exchange or a  Ensure mass transfer (dialysis) between two liquids afford that separated by the hollow fiber wall are, however, a passage of liquid through the Pores can be prevented. Typically, therefore, the pores have Dimensions smaller than 1 µm. The coated hollow threads are said to a porosity of 10 to 50%, preferably 20 to 40% exhibit. When grafting on polyvinylidene chloride a reduction in the original porosity can occur ten, especially if more than 40 to 50 wt .-% polyvinyli the grafted chloride is based on the weight of the used, porous hollow thread. Preferably, as an off a hollow thread with particularly good porosity used to account for this decrease in porosity It remains surprising, however, that in this way a coating of biocompatible carbon material that hemocompatibility and anti The thrombogenicity of the porous hollow fibers is significantly improved, without removing their porosity.

Stretched porous hollow threads are preferably used. The orientation of the carbon obtained by stretching chains facilitate the application of a uniform loading layering made of biocompatible carbon material. Preferential become wise for the gas phase graft polymerization Conditions provided for the epitaxial growth of the Guide the polyvinylidene chloride layer on the thread material. Here, the grafted polyvinylidene chloride takes over Structure of the thread material.

Mo is used as the starting material for creating the top layer monomeric vinylidene chloride (1,1-dichloroethylene). Commercially available accessible, pure, stabilized preparations have a Purity greater than 99.5%. The boiling point is 30 to 32 ° C. A degassing chamber is recommended before use action at reduced pressure. That as the starting material  monomeric vinylidene chloride used should be air-free.

In the context of the method according to the invention, in a Gas phase from monomeric vinylidene chloride a graft risations response induced to an even polyvi nylidene chloride layer on the given hollow thread graft. This graft polymerization is a radical one based polymerization reaction. This graft polymer Rization can be induced in various ways, at for example with the help of laser light excitation. Basically graft polymerization processes could also be used those described in the British Patent referenced above documents 856,329 and 801,531 are described; however read the uniformity of the grafted layer and the achievable yield left something to be desired. Preferably one is radiation-induced graft polymerization using ionization render radiation provided because such a chemical bond the coating via covalent C-C bonds to the thread mate rial is achievable, and get an effective coating can be. In particular, preferably serves as the radiation source especially a gamma radiation source. Gamma rays indicate high penetration. The radiation can do that Penetrate vessel material (e.g. stainless steel). Be neighboring and at a distance from the gamma radiation source can meh rere closed reaction vessels are provided in which the graft polymerization reaction is carried out. Irradiation with electron beams from an electro NEN accelerator is less useful because it only ver equally thin layers can be irradiated. A suitable radiation source can be, for example, with the Iso top co.

In the radiation-induced grafting of polyvinyli The chloride on porous hollow threads made of polypropylene is used  preferably worked under such conditions that inner half of the reaction vessel a dose rate of 0.1 to 1.5 W / kg (10 to 150 rad / sec) radiation material is achieved. Before the exposure to radiation during the whole Duration of the graft polymerization reaction provided.

With the help of this radiation-induced gas phase graft polymerization can produce a uniform polyvinylidene chloride Layer created and chemically attached to the polyolefin material Hollow thread can be bound without the mechanical intrinsic affect the properties of the thread material substantially. The polyvinylidene chloride is attached via covalent C-C bonds the carbon chain of the thread material is bound. The Layer thickness of the grafted polyvinylidene chloride layer can be set within wide limits.

Such an amount of polyvinylidene chloride is preferred grafted, which the porosity and strength of the Starting thread reduced only to an acceptable extent, which however, after coating or dehydrochlorination Coating of carbon material, which provides the Haemocompatibility and anti-thrombogenicity clearly improved sert, compared to uncoated starting threads. He obviously it only comes down to a coating of such Ab cuts and "active spots" on the thread surface that are accessible from the blood and the active blood components.

The radiation-induced graft polymer mentioned above tion is preferably in a quiescent gas phase from Vi performed nylidene chloride. It is still advisable the output hollow filament with respect to the radiation source because of. In the case of wrapped porous hollow such coils can ro continuously around their axis be animals. Furthermore, mild reaction conditions become  gene and instead a longer reaction time see. In graft polymerization, the formation of a liquid vinylidene chloride phase on and / or on the thread material to be avoided. This would become uneven Products. The monomer pressure is preferably at kept about 500 to 700 mbar. The monomeric vinylidene chloride condenses at around 20 ° C. The thread material and the mate rial of the reactor wall is preferably at a higher temperature held. A temperature of 25 is particularly preferred up to 50 ° C for the thread winding and for the reactor wall. The Graft polymerization is exothermic and longer Duration could increase the thread temperature up to about 40 ° C occur. On the other hand, the thread temperature should be above preferably do not rise above 30 to 40 ° C. Thu The radiation power is set accordingly (preferably 0.1 to 1.5 W / kg of radiation, as above executed). Instead of a higher dose rate, sooner a longer reaction time is provided. Preferably the radiation-induced graft polymerization continuously carried out over a period of at least 20 hours; also a duration of 30 to 40 hours is not uncommon in practice usually. The radiation exposure is preferably effected throughout the duration of the gas phase graft polymer tion.

In this gas phase graft polymerization, the mono penetrates mere vinylidene chloride in the thread material. It takes place chemical bonding and anchoring of the poly formed vinylidene chloride within the thread. More surprising The existing porosity in the starting thread becomes wise not eliminated at least not completely eliminated. Wei then the polyvinylidene chloride grows evenly on the smooth sections of the thread surface and forms there an even and dense layer. Preferably be such conditions are chosen so that the structure of the Polyvi  nylidene chloride layer corresponds to the thread structure (epitax ial growing up). This structural homology is desirable worth it to later create an oriented carbon layer aim. The growth of the polyvinylidene chloride layer is not limited by inherent factors and, according to Be love to continue as long as there is enough porosi The strength and strength of the hollow thread is retained.

All of these reaction conditions are aimed at a mild polyvinylidene chloride Obtain layer that chemically ge to the thread material tied without damaging the starting thread. Under These conditions can also be wrapped in polypropylene hollow threads are treated.

Porous hollow filaments made of polypropylene can be used under these conditions of the radiation-induced gas-phase graft polymers rization preferably to 1 part by weight of thread material 0.1 to 1.2 parts by weight of polyvinylidene chloride are grafted on, per 1 part by weight of thread material are particularly preferred Grafted on 0.4 to 0.6 parts by weight of polyvinylidene chloride. On a thread wrap with 100 parts by weight of polypropylene Hollow threads preferably become 40 under these conditions grafted to 60 parts by weight of polyvinylidene chloride, so that this thread wrap after grafting a weight of 140 to 160 parts by weight. Single is required Lich such an amount of polyvinylidene chloride, which after the Dehydrochlorination is a top layer made of biocompatible Carbon material that provides hemocompatibility here especially with regard to hemolysis, accumulation of Leukocytes, activation of the complement complex and acti crossing of the coagulation cascade up to thrombus formation, this coated hollow filaments significantly improved in Comparison to known hollow threads made of polypropylene. Ande on the other hand, the coating should be as low as possible  will last as long as the desired hemocompatibility is guaranteed to the porosity of the output fibers and the mechanical properties of the coated hollow fibers not interfere unnecessarily.

Taking these boundary conditions into account is preferred a graft of about 40 to 60 parts by weight of polyvinyli denchloride per 100 parts by weight hollow fiber material made of poly propylene provided. After a largely exhausting Dehydrochlorination thus remain per 100 parts by weight Hollow thread material about 10 to 15 parts by weight of carbon material. In other words, it contains these conditions Coated thread produced around 9 to 13 % By weight of carbon material, based on the total weight of the coated hollow thread.

Chlorine must be removed from the polyvinylidene chloride layer Hydrogen (HCl) largely completely split off and removed (dehydrochlorination) to this polyvinyli the chloride layer into a layer of biocompatible Koh convert material. Furthermore, dehydrochlo ration conditions are selected, which the thread material and here in particular its strength properties possible affect little.

It is possible to do this dehydrochlorination with the help of me metallic sodium and / or sodium amide in liquid ammo perform niak. This implementation can be done on a laboratory scale Basically, it takes a long time to react times of 100 hours and more and working under high pressure (50 bar and more) in the autoclave. For a ge the product appears for commercial or industrial use activity too low; furthermore, unreacted sodium amide decomposed and removed, for example with considerable Amounts of methanol.  

It is still possible to gas this dehydrochlorination form ammonia in the gas phase. Good results However, nits were only obtained on very small samples. Sufficient reaction speed requires tempe temperatures above 100 ° C. On the other hand, the substrate temperature temperature, especially for polypropylene hollow threads 100 to 120 ° C. do not exceed. The dehydrochlorination is exothermic. When working in the gas phase, the possibility is one Heat dissipation is limited and it can easily cause overheating of hollow fibers enter. Furthermore, when working in the Gaseous phase is the ammonium produced during dehydrochlorination chloride (NH₄Cl) cannot be easily removed.

It is preferably provided that this dehydrochlorination perform hot aqueous alkaline solution. Preferential wise is a wrap made of polypropylene hollow threads with the grafted polyvinylidene chloride layer are introduced into this hot aqueous alkaline solution and at least for several hours within this solution held. Alternatively, this can be hot aqueous alkaline Solution can be pumped through a reaction space in which the ver with the grafted polyvinylidene chloride layer see thread winding.

Preferably, the boiling point of the aqueous Solution worked. A working temperature of around 80 up to 100 ° C has proven itself and is preferred see. Damage can occur when working below 100 ° C of the thread material can be safely prevented. The boiling point the solution prevents a higher thread temperature. Further water has a high heat capacity. When working in aqueous solution may have a higher reaction rate achieved and adjusted because of the heat generated can be easily removed. That with dehydrochlorination The ammonium chloride formed dissolves easily in aqueous solution solution and can be easily removed.  

Conventional bases and Salts are used, such as the hydroxides of Na trium and potassium or the carbonates and bicarbonates of Alkali metals and alkaline earth metals. When working in watery The addition of a NaOH or KOH solution is recommended Phase transfer catalyst such as tetrabutylammonium bromide [(CH₃-CH₂-CH₂-CH₂) ₄N] Br.

A dehydrochlorinating agent is particularly preferred hot concentrated aqueous ammonia solution used. Well an ammonia concentration of 20 to 35 is suitable % By weight. Preferably, the commercially available aqueous ammonia solution (ammonium hydroxide) with an ammo worked niak concentration of 25 wt .-%. Preferably is saturated with one at the respective temperature aqueous ammonia solution and under an appropriate Ammonia pressure worked. For example, under an ammonia pressure up to about 6 to 8 bar worked will. For example, particularly good results have been obtained received under the following conditions:

• - An ammonia concentration in the hot aqueous Solution of about 25% by weight,
• - a working temperature of about 96 ° C and
• - An ammonia pressure of about 6 bar.

The dehydrochlorination is carried out until the Residual chlorine content of the coated hollow thread to less than 6%, based on the chlorine content of the grafted polyvinylidene chloride. Among the ver equally mild dehydrochlorination conditions are here required for a period of at least 20 hours. Each Depending on the application, dehydrochlorination can also be used for a duration of about 30 to 40 hours.

The dehydrochlorination is preferably carried out until the residual chlorine content of the coated hollow thread is reduced to less than 3%, in particular less than 2%, based on the chlorine content of the grafted polyvinylidene chloride. The structurally bound chlorine, ie the chlorine contained in the polyvinylidene chloride residues of the coating, can be detected, for example, by means of infrared spectroscopy using a band at approximately 1050 cm ^-1 . With a residual structural chlorine content of less than 2%, a coating of essentially pure carbon material with excellent biocompatible properties is obtained.

After the hydrochlorination, the grafted-on polyvinylidene chloride provides a carbon material which has a density of about 1.8 g / cm 3. The spectroscopic investigations confirm absorptions at 2180 cm ^-1 and a broad band at about 1600 cm ^-1 in the IR spectrum. The absorption at 2180 cm ^-1 is assigned to the valence vibration of the C≡C triple bond in linear conjugated carbine structures. The absorption at 1600 cm ^-1 is assigned to conjugated C = C double bonds. From all of this, the inventors conclude, without being bound by it, an oriented carbine structure in the carbon material obtained after extensive dehydrochlorination.

Typically, the proportion of this makes carbon mate rial about 5 to 20 wt .-% of the total weight of the coating made of polypropylene hollow thread; d. H. the finished thread with biocompatible carbon coating is 80 to 95% by weight of polypropylene and 20 to 5% by weight of the Carbon material, based on the total weight of thread.

Following the dehydrochlorination, the coated hollow thread is washed continuously, preferably with hot water, in order in particular to remove ammonium chloride. The ammonium chloride content can be detected in the infrared spectrum using a band at approximately 1400 cm ^-1 . The ammonium chloride content should preferably be reduced to less than 0.1% by weight, based on the weight of the coated hollow thread. A wash treatment with hot water that has a temperature of about 80 to 90 ° C. for several hours is well suited for this purpose.

Following such a washing treatment, heat can be applied treatment are provided, the thermosetting of the Thread structure causes and residual traces of ammonium chloride rid eliminated by sublimation. Such a heat treatment is preferably placed in a vacuum thermal cabinet under a vacuum less than 0.1 mbar carried out without interruption is pumped. Such heat fixation to a wic kel wound coated hollow fibers can for example wise at 135 ° C for about 1.5 hours in Va be carried out in a vacuum. With the help of such a heat can also traces of ammonium chloride by sub Limation be eliminated.

For production in a commercial or industrial environment The porous, endless hollow fibers are preferred under controlled conditions on a perforated Winding carrier (sleeve, cartridge, cartridge) wound up, and in the form of this wrap in the reactor to carry out radiation-induced gas-phase graft polymerization and then concentrated in the dehydrochlorination reactor ter hot aqueous ammonia solution introduced. The Reak tion takes place through the winding and covers the whole te wound endless material. For this it is advisable if the thickness of the winding on the perforated wick not a layer thickness of about 10 to 20 mm exceeds, and / or if the density of the winding between about 0.40 and 0.60 g / cm³ is maintained. Under these conditions  Good penetration of the entire endless mat is required rials achieved. In a reactor for radiation induced Gaseous phase graft polymerization can incorporate multiple coils sets and be treated at the same time. For dehydrochloria each winding is preferably in its own reac tion vessel used for a good flushing of the up to achieve wound thread mass. Here, however, several can Reaction tubes parallel to each other to form a battery be summarized, through which the hot alkaline dehy drochloring agent is pumped through. Despite the ver equally long treatment times can be a high pro productivity can be achieved.

There are indications that when grafting polyviny lidenchloride on an endless hollow fiber the length of this Hollow thread increases. The causes are not yet fully understood and seem with the degree of porosity and related to the structure of the micropores. (At the grafting of polyvinylidene chloride on stretched Solid threads made of polypropylene experience such an increase in length not.) With a grafting of 60 parts by weight of Polyvi nylidene chloride per 100 parts by weight of polypropylene hollow thread For example, a length increase of about 8% was observed pays attention to given length sections of the output threads. This makes the wrap looser and looser. In this It is advisable to use the gas phase Graft polymerization to rewind the coated hollow fibers and under controlled conditions on a new wick winding carrier in order to in turn a density of the wic kels set for subsequent dehydrochloria tion in the liquid phase is well suited. The hot watery one Solution can flow continuously through the perforated wick lung carrier and pumped through the wound layer will.  

The following examples serve for further explanation the invention without restricting it.

Comparative example

This comparative example serves for general explanation this new technology for applying a coal layer of fabric on the circumference of a solid thread made of polypropylene.

One of 36 orientated single cases serves as the starting material the polypropylene yarn with a length reference mass of 8 tex. This starting thread is for the Implementation of the measures provided according to the invention a cylindrical perforated cartridge made of corrosion-resistant Steel rewound (length 185 mm, outer diameter 30 mm). It such winding conditions are provided that lead to a Winding thickness of about 14 mm and to a thickness of the wick lead from about 0.50 to 0.55 g / cm³. Among these be Conditions are around 170 to 180 g on each wrap Yarn.

The radiation-induced gas phase graft polymerization is by direct action of gaseous vinylidene chloride performed on the wrap. For this purpose, the wrap is in a closable and evacuable reactor used to a vessel is connected via a shut-off valve into which liquid, monomeric vinylidene chloride can be introduced. To inserting several coils into the reactor becomes the reac gate closed and up to a residual pressure of about 10 mbar evacuated. The previously degassed under vacuum, liquid Ge vinylidene chloride is sucked into the feed vessel. The The amount of vinylidene chloride introduced depends on the Total amount of yarn to be coated and the desired amount Layer thickness. The vinylidene introduced into the feed vessel chloride is degassed again there. Then the barrier valve opened, and one in the reactor at room temperature  Gas phase formed from monomeric vinylidene chloride. The tempe rature of the reactor is kept at about 30 ° C. The steam Pressure of the monomeric vinylidene chloride is between about 500 and kept 700 mbar. The condensation of liquid mono meres on the substrate should be prevented. With the help of a Radiation source associated with the radioactive isotope Co the radiation is carried out. To do this the reactor is placed in a protected space in which the radiation source turned on from a protected position can be brought. For example, the radiation source raised from a deep hole in the floor of the room so that the gamma radiation can flood the reactor. Within the reactor has a dose rate of about 0.15 W / kg Be radiation set (about 15 rad / sec). The irradiated is carried out throughout the graft polymerization leads. The speed of rotation of the winding is related to the Adjusted dose rate. At the beginning of the reaction, the Mo nomer in the feed vessel a temperature of about 17 to 20 ° C. on. Because of the heat released during the polymerization the temperature rises to about 35 in the course of the reaction up to 45 ° C. The thread temperature should not exceed 40 ° C. Under these conditions, about 65 to 80 parts by weight of poly vinylidene chloride per 100 parts by weight of polypropylene yarn grafting is a reaction time of about 30 to 35 Hours required. The end of the reaction is after Pressure drop in the system achieved by the consumption of the Monomers is caused. After the reaction has ended, the remaining monomer vapors over one with liquid nitrogen pumped cooled trap, and then the reactor with air blown through. The bobbins with the coated yarn are removed from the reactor.

The coated yarns are again perforated Cartridge rewound to turn with a suitable wrap Obtain density for the subsequent dehydrochlorination.  

Hot 25% ammonia solution is used for dehydrochlorination through the perforated winding carrier and the on the Winding carrier located pumped. This process is with the help of temperature and pressure differences in the zu guide vessel and regulated in the collecting container. Every wrap is used in a separate reactor. The entire An layer comprises several react connected in parallel goals. Before the start of the reaction, the whole plant is up to evacuated a residual pressure of about 0.1 mbar. Subsequently the ammonia solution is pumped into the feed vessel and heated to the specified temperature. The solution is out the feed vessel over the coils into a collecting container and then from the container over the wrap in the feed vessel is pumped. Essentially, one Temperature of 96 ° C, with an ammonia concentration of 25% and under a pressure of the ammonia vapors of about 6 bar worked. Under these conditions, the dehydrochlo for about 35 hours. Subsequently the dehydrochlorinated threads are washed with hot water wash to by-product ammonium chloride to remove. For washing up, use hot distilled water from 80 to 95 ° C for 5 hours through the winding.

Subsequently, the dehydrochlorination is heat-set th and washed threads made in the course of subsequent use (e.g. for sterilization measures) prevent heat shrinkage of the threads and traces to be completely removed from ammonium chloride (sublimation). The wraps are heat-set for at least 1.5 hours long in a vacuum drying cabinet under a vacuum ner 0.1 mbar kept at a temperature of about 135 ° C.

After heat setting, the residual content of structural chlorine and ammonium chloride can be determined on thread samples. "Structural" chlorine is understood to mean the chemically bound chlorine contained in polyvinylidene chloride residues. This chemically bound chlorine absorbs in the infrared spectrum at around 1050 cm ^-1 ; the ammonium chloride absorbs at around 1400 cm ^-1 . Under these conditions who receive the package with yarns containing less than 2% structural chlorine, based on the chlorine content of the original polyvinylidene chloride layer, and packages containing less than 0.1% ammonium chloride, based on the weight of the coated Yarns.

The coated yarns can then be made to standard coils are rewound for delivery to Wei processors are provided. With this rewinding preferably a crosswise winding is provided. The company the mass should not exceed 250 g.

example

Endless, porous hollow fibers are used as the starting material Polypropylene manufactured by HOECHST CELLANESE CORPORATION the trade names "CELLGARD X 10 240" (porosity 30%) or "CELLGARD X 20 240" (porosity 40%) will. According to the manufacturer's specification, these indicate Hollow fibers with an outside diameter of 300 µm, an inside diameter of 240 µm and a wall thickness of 30 µm. The porosity is 30% or 40%, determined according to the U.S. standard ASTM D-2873. The pores have dimensions (length × Width) of about 0.15 µm × 0.05 µm. This endless Hohlfa Serums are perforated in amounts of about 1 to 10 g Titanium cartridges wound up and in this form in one Reactor introduced, which for radiation chemical investigation is designed. A vessel is attached to the reactor closed, in which monomeric, liquid vinylidene chloride is located. The monomer is treated by vacuum vented. The reactor is in the radiation field Gamma radiation source can be introduced, which is associated with the isotope Co  is equipped. The power inside the reactor is about 1.4 W / kg of radiation (about 140 rad / sec). The Irradiation is used throughout the gas phase graft poly merization carried out. The temperature of the reactor will kept at 30 ° C; the liquid monomer is with a tem temperature of 28 ° C fed into the reactor.

The reactor is opened at certain intervals. The samples are removed and weighed to determine the amount of grafted polyvinylidene chloride. With FIG. 1, up the hollow fiber with a porosity of 30% grafted polyvinylidene amount is shown as a function of time. Fig. 2 shows a similar representation for the hollow thread with the porosity 40%. The grafted amount of polyvinylidene chloride is given in percent by weight, based on the weight of the starting thread. It can be seen that there is an essentially linear dependence on the duration of treatment up to the grafting of about 50% by weight of polyvinylidene chloride. The entire course of the curve can be described with a second-order polynomial.

In these grafting experiments, the surprising observation that the thread length increases is made compared to the treatment of solid polypropylene threads. This leads to the fact that the density of the winding becomes looser or looser and that free windings "twist". The increase in thread length during grafting was also determined experimentally. The results are shown in FIG. 3. The dashed line relates to the hollow thread with the porosity 30%; the continuous line concerns the hollow thread with a porosity of 40%. Obviously, up to about 60% by weight of polyvinylidene chloride, the thread length increases by about 8%. Although this phenomenon is not yet fully understood, the inventors suspect that the gaseous vinylidene chloride also penetrates into the cracks and pores that cause the porosity, and that the grafting leads to the spreading of the thread layers in the longitudinal direction of the thread.

Grafted on to the various samples thus obtained polyvinylidene chloride will largely exhaust one de Dehydrochlorination carried out to the polyvinylidene convert chloride to a carbon material. About who samples in a concentrated aqueous solution for 30 hours Ammonia solution, which has an ammonia concentration tion of 25%. After this dehydrochlorination carries the content of remaining "structural" chlorine less than 6 wt .-%, based on the chlorine content of the poly vinylidene chloride.

On the starting threads, on the threads with grafted poly vinylidene chloride and to the after dehydrochlorination The threads held are the dimensions with those in the laboratory existing tools determined. The results are in the shown in the table below.  

Table 1

Obviously, grafting and dehydrochlorination have none significant effects on the thread parameters.

It was also estimated to what extent the grafting and dehydrochlorination changed the originally given porosity of the hollow fibers. This estimate was made indirectly by determining the gas permeability. For this purpose, each 6 thread patterns, which have a length of 15 cm, were placed in a glass tube and slightly stretched. On one side, the thread ends were closed with a medium pressure-tight adhesive. The other thread ends were connected pressure-tight to a vessel in which there was an overpressure of about 200 to 260 bar compared to the atmospheric pressure. The decrease in pressure in the pressure vessel was checked under the same conditions, which under these conditions could only be achieved by the passage of gas through the wall of the hollow fibers. The results obtained are shown in FIG. 4. The gas permeability thus determined decreases with increasing amount of grafted polyvinylidene chloride. Furthermore, the decrease in the starting thread with the porosity is 30% greater than in the starting thread with the porosity 40%.

These results confirm that the starting hollow thread with a porosity of 40% even after the grafting of 50 up to 60 wt .-% polyvinylidene chloride, based on the Aus thread weight, still about 60% of the gas permeable speed of the starting thread (= 100%). So that's the Evidence has been provided that the grafting of polyvinylidene chloride and the conversion of polyvinylidene chloride into one Carbon material does not completely replace the original porosity eliminated.  

By suitable selection of the starting threads with as possible high porosity and by suitable selection of the graft conditions can be hollow threads that continue to be have sufficient porosity and yet a solid adhesive coating made of a biocompatible carbon Have material that has the hemocompatible properties significantly improved compared to the untreated out thread.

Also first attempts to determine the change in mechani strength, especially elongation at break, lead to the Er result that it is probably not recommended, essential more than 60 wt .-% polyvinylidene chloride on the starting grafting threads.

Another important aspect of the invention relates to Use of the porous hollow threads according to the invention, with a coating of biocompatible carbon material are provided. Typically they have coated Hollow threads have a porosity of 10 to 50%, especially of 20 to 30% and are used as exchange materials and / or used as a semipermeable membrane in devices that outside the human body with blood and / or plasma come into contact. Such devices include for example oxygen generators, dialysis machines, various fil ter and heat exchanger. Depending on the application, the Hollow threads adapted to diameter, wall thickness and porosity on. Suitable as substrates for the Be layering porous hollow threads made of polypropylene commercially available. When choosing the hollow thread is to ensure that the measures for applying a Coating made of biocompatible carbon material originally reduced porosity by about 10 to 20% who can. Without being limited, are preferred  Applications of this type set out in claims 36 to 42 leads. In these applications, the hollow filaments can be in shape individual threads, used as mats or as wraps will. Exchange areas of around 0.3 to 3.0 m² required. There are about 6000 to 400,000 of them Hollow threads required. The use of the invention Hollow threads in such devices reduce the requirement heparinization of the blood and reduces the Damage to blood components when pumping the Blood from such devices.

Claims (42)

1. Biocompatible, porous hollow thread made of a polyolefin material, characterized in that the hollow thread is provided with a coating made of a biocompatible carbon material; and this coating is available through

• - Introducing the pre-formed, porous hollow thread into a gas phase made of monomeric vinylidene chloride (1,1-dichloroethylene);
• Inducing a graft polymerization reaction and grafting a uniform layer of polyvinylidene chloride onto the hollow fiber; and
• - Elimination and removal of hydrogen chloride (dehydrochlorination) to a residual chlorine content of less than 6%, based on the chlorine content of the original polyvinylidene chloride layer.

2. Biocompatible, porous hollow thread according to claim 1, characterized in that a radiation-induced gas phase graft polymerization with the help of ionizing radiation, in particular with Gamma radiation has occurred. 3. Biocompatible, porous hollow thread according to claim 2, characterized in that the graft polymerization at a medium energy dose power of about 0.1 to 1.5 W / kg of radiation has been carried out. 4. Biocompatible, porous hollow thread according to claim 2 or 3, characterized in that
radiation-induced gas phase graft polymerization has taken place over a longer period of at least 20 hours; and
the exposure to radiation has occurred during the entire gas phase graft polymerization. 5. Biocompatible, porous hollow thread according to one of the An sayings 1 to 4, characterized in that 0.1 to 1.2 parts by weight per 1 part by weight of hollow fiber material Polyvinylidene chloride have been grafted on, in particular per 1 part by weight of hollow fiber material 0.4 to 0.6 part by weight Parts of polyvinylidene chloride have been grafted on. 6. Biocompatible, porous hollow thread according to one of the An sayings 1 to 5, characterized in that dehydrochlorination in a hot aqueous alkali solution.   7. A biocompatible, porous hollow thread according to claim 6. characterized in that the dehydrochlorination in a hot concentrated aqueous ammonia solution. 8. Biocompatible, porous hollow thread according to one of the An sayings 1 to 7, characterized in that the coated porous hollow thread has a porosity of 10 up to 50%, in particular a porosity of 20 to 40% having. 9. Biocompatible, porous hollow thread according to one of claims 1 to 8, characterized in that the hollow thread material is polypropylene;
the coating is made of carbon material having a density of about 1.8 g / cm³; and
the weight of the carbon material makes up 5 to 20% by weight of the total weight of the coated hollow thread. 10. A method for producing biocompatible, porous hollow fibers according to one of claims 1 to 9, characterized by the following process steps:

• - A pre-formed porous hollow thread consisting of a polyolefin material is introduced into a tightly closable vessel;
• - The vessel is charged with monomeric gaseous vinylidene chloride (1,1-dichlorethylene);
• - A graft polymerization reaction is induced inside the vessel in order to graft a uniform layer of polyvinylidene chloride onto the thread material;
• - The hollow thread, which is wholly or partly provided with a coating of polyvinylidene chloride, is exposed to reaction conditions which lead to cleavage and removal of hydrogen chloride (dehydrochlorination);
• - This dehydrochlorination is carried out at least until the residual chlorine content of the coating is less than 6%, based on the chlorine content of the original polyvinylidene chloride layer.

11. The method according to claim 10, characterized in that a radiation-induced gas phase graft polymerization with the help of ionizing radiation. 12. The method according to claim 11, characterized in that a gamma radiation source is used. 13. The method according to claim 12, characterized in that a radiation source is used, which is the isotope  Co contains. 14. The method according to claim 12 or 13, characterized in that in the reaction vessel an average energy dose rate of about 0.1 to 1.5 W / kg of radiation material is provided. 15. The method according to any one of claims 10 to 14, characterized in that in the course of the radiation-induced gas phase graft polymerization of the hollow thread, in particular a winding  from wound, endless hollow fiber with respect to the Radiation source is moved. 16. The method according to any one of claims 10 to 15, characterized in that worked in a dormant gas phase from vinylidene chloride is tested. 17. The method according to any one of claims 1 to 16, characterized in that during the radiation-induced gas phase graft poly merization a condensation of liquid vinylidene chloride on the thread material is prevented. 18. The method according to any one of claims 11 to 17, characterized in that
the radiation-induced gas phase graft polymerization is carried out for at least 20 hours; and
the radiation exposure is carried out during the entire gas phase graft polymerization. 19. The method according to any one of claims 10 to 18, characterized in that in the course of the graft polymerization to 1 part by weight Thread material 0.1 to 1.2 parts by weight of polyvinylidene chloride are grafted on, in particular to 1% by weight Part of thread material 0.4 to 0.6 part by weight of polyvinylidene chloride are grafted on. 20. The method according to any one of claims 10 to 19, characterized in that dehydrochlorination in hot, aqueous, alkaline Solution is carried out.   21. The method according to claim 20, characterized in that the dehydrochlorination in a hot concentrated aqueous ammonia solution is carried out. 22. The method according to claim 21, characterized in that dehydrochlorination at an ammonia concentration from 20 to 35% by weight in hot, aqueous solution to be led. 23. The method according to claim 21 or 22, characterized in that the dehydrochlorination in a hot, at the respective temperature saturated with ammonia aqueous solution is carried out. 24. The method according to any one of claims 20 to 23, characterized in that dehydrochlorination at a temperature between 80 and 100 ° C is carried out. 25. The method according to any one of claims 21 to 24, characterized in that dehydrochlorination under ammonia pressure is carried out. 26. The method according to any one of claims 20 to 25, characterized in that the dehydrochlorination for at least a period Is carried out for 20 hours. 27. The method according to any one of claims 20 to 26, characterized in that  the dehydrochlorination is carried out until the residual chlorine content in the top layer is less than 3%, especially to less than 2%, based on the chlorine content of the original poly vinylidene chloride layer. 28. The method according to any one of claims 20 to 27, characterized in that after dehydrochlorination the coated hollow thread is washed sufficiently with hot water, in particular special also to remove ammonium chloride. 29. The method according to claim 28, characterized in that after the washing treatment, a heat treatment of the coated hollow thread under reduced pressure is carried out in order to achieve heat setting and traces of residual ammonium chloride Remove sublimation. 30. The method according to any one of claims 10 to 29, characterized in that
the endless porous hollow thread is wound on a perforated winding support (sleeve, cartridge, cartridge), and
the gas phase graft polymerization and the dehydrochlorination is carried out on such coils. 31. The method according to claim 30, characterized in that the strength of the winding on the perforated winding carrier is 10 to 20 mm. 32. The method according to claim 30 or 31, characterized in that  the density of the winding between 0.40 and 0.60 g / cm³ is held. 33. The method according to claim 32, characterized in that following the gas phase graft polymerization and before the dehydrochlorination a winding around coated hollow threads is made to turn a new wrap with a winding density of 0.40 to 0.60 g / cm³ to generate and the dehydrochlorination on these new Winding is carried out. 34. The method according to any one of claims 30 to 33, characterized in that a washing treatment following the dehydrochlorination and then heat setting under is carried out under reduced pressure. 35. Use of a biocompatible, porous hollow thread after one of claims 1 to 9, the in the form of hollow threads made of a polypropylene material is present, these hollow threads on their outer circumference a coating of biocompatible carbon material have, and wherein these hollow threads have a porosity of Have 10 to 50%, in particular 20 to 40%, as exchange materials and / or as semipermeable Membrane in devices outside the human Come into contact with blood and plasma. 36. Use according to claim 35, the hollow threads having an inside diameter of 100 to 400 µm, an outside diameter of 250 to 450 µm and have a wall thickness of 20 to 80 µm as thawing shear material and / or semipermeable membrane in oxy generators for gas exchange between two media.   37. Use according to claim 35, such hollow threads having an inside diameter of 200 up to 400 µm and a wall thickness of 30 to 50 µm sen as an exchange material and / or semipermeable membrane in dialysis filters. 38. Use according to claim 35, such hollow threads having an inside diameter of 200 up to 400 µm and a wall thickness of 30 to 60 µm sen as an exchange material and / or semipermeable membrane in hemoconcentrators. 39. Use according to claim 35, such hollow threads having an inside diameter of 50 to 400 µm and a wall thickness of 10 to 100 µm have as Exchanger material and / or semipermeable membrane in Plasma filters. 40. Use according to claim 35, such hollow threads having an inside diameter of 10 to Have 30 µm as an exchange material in blood filter membranes. 41. Use according to claim 35, such hollow threads having an inside diameter of 10 to Have 200 µm, as heat exchange fibers for oxygenators. 42. Use according to claim 35, such hollow threads having an inside diameter of 0.3 to Have 100 µm, for the production of infusion membranes.