DE102009023651B4 - Process for the production of a polyethylene doped with a stabilizer and use of a polyethylene produced by this process - Google Patents

Abstract

A process for the production of a polyethylene doped with a stabilizer, wherein a polymerization of ethylene is carried out in the presence of a stabilizer and a catalyst, characterized in that an antioxidant from the group consisting of vitamin E, vitamin C and combinations thereof and as a catalyst a Mixed catalyst comprising a precatalyst and a cocatalyst is used, a chromium-containing non-metallocene being used as the precatalyst and an alkylaluminoxane being used as the cocatalyst and the ethylene being passed into a solution containing the stabilizer, the catalyst and a solvent or solvent mixture for the polymerization becomes.

Description

The present invention relates to a production method for polyethylene which is doped with a stabilizer, as well as the use of a polyethylene produced by the method for the production of a medical device.

Ultra-high molecular weight polyethylene (UHMWPE, ultra-high molecular weight polyethylene) is used to a particularly large extent for the production of orthopedic implants. For example, around 70% of all hip and knee endoprostheses used worldwide have sliding surfaces made of UHMWPE. Although these have proven themselves in everyday clinical practice for more than 30 years, their lifespan is usually limited to 10 to 15 years. The reason for the limited service life are oxidative damage mechanisms of the UHMWPE, which take place in the patient's body. This can increase the abrasion of the polymer material dramatically. In addition, inflammation in the area around the implant can occur. In many cases, expensive revision operations are therefore required.

In the EP 1 161 489 B1 describes a process for producing a UHMWPE doped with a stabilizer, such as, for example, α-tocopherol. The process is based on the diffusion principle, whereby the stabilizer is pressed into a UHMWPE cube by means of supercritical carbon dioxide. A corresponding diffusion process for cross-linked UHMWPE is from EP 1 624 905 B1 known. However, the disadvantage of these diffusion processes is that they are complex and, in particular, costly. A particular problem here is that practically no reasonable penetration depths of the stabilizer in UHMWPE can be achieved in foreseeable periods of time. The solubility of the stabilizer in UHMWPE can in principle be increased by increasing the temperature. However, there is a risk that the polymer will be “overloaded” with the stabilizer, with the result that excess stabilizer will be “sweated out” again after the diffusion process has ended. In order to achieve an even distribution of the stabilizer in UHMWPE, the EP 1 624 905 B1 an annealing step proposed. However, it is disadvantageous that long tempering times are required for this, which overall lead to a considerable increase in the production time for a UHMWPE which is doped with a stabilizer.

Processes for producing polyolefins using phosphorus-containing stabilizers are disclosed in US Pat EP 0 710 677 A2 as U.S. 4,824,885 known.

A polymer material with an antioxidant and without endocrine disrupting compounds is from the US 6,894,093 B2 known.

The present invention is therefore based on the object of providing an alternative production method for a stabilizer-provided or doped polyethylene which causes the stabilizer to be distributed as homogeneously as possible in the polyethylene, is simple to implement and inexpensive and is characterized in particular by shortened production times.

This object is achieved by a manufacturing method having the features of independent claim 1. Preferred embodiments of the manufacturing method are the subject matter of the dependent claims 2 to 12. Another subject matter of the invention is the use of a polyethylene manufactured by the method for manufacturing a medical device according to the claims 13 to 15.

The process according to the invention is a process for the production of a polyethylene provided or doped with a stabilizer, namely an antioxidant (antioxidant or oxidation inhibitor), a polymerization of ethylene being carried out in the presence of a stabilizer, namely an antioxidant, and a catalyst .

In the process according to the invention, doping or equipping with the stabilizer does not take place, as is known from the prior art, on a molded polyethylene body, for example a corresponding cube, but rather during the production of the polyethylene, i.e. during the polymerization of ethylene to polyethylene. As a result, a uniform or homogeneous distribution of the stabilizer in the polyethylene can be achieved with particular advantage, without the need for lengthy post-treatment steps, in particular in the form of tempering. This leads to a considerable shortening of the production time and to a reduction in the thermal load on the polyethylene material. Furthermore, material properties of the polyethylene to be produced can be regulated in a simple manner, for example by selecting the reaction time, the reaction temperature and / or the reaction pressure.

The polymerization is carried out as a solution polymerization. For the polymerization, the ethylene is first passed into a solution which contains the stabilizer, the catalyst and a suitable solvent or solvent mixture. For example, to prepare the solution, first the catalyst and then the stabilizer can be dissolved in the solvent or solvent mixture. In principle, aliphatic hydrocarbons, aromatic hydrocarbons and / or halogenated hydrocarbons can be used as solvents. Examples of aliphatic hydrocarbons can be selected from the group consisting of pentane, hexane, heptane, octane, decane, kerosene, cyclobutane, methylcyclobutane, cyclohexane, methylcyclohexane, and mixtures thereof. Suitable aromatic hydrocarbons can be selected from the group consisting of benzene, toluene, ortho-xylene, meta-xylene, para-xylene, ethylbenzene, cumene, cymene, and mixtures thereof. Suitable halogenated hydrocarbons can be selected, for example, from the group consisting of aliphatic fluorocarbons, aromatic fluorocarbons, chlorobenzene, dichlorobenzene, trichlorobenzene and mixtures thereof. As a rule, dried, ie essentially anhydrous, solvents are used.

The stabilizer used is preferably a compound which essentially does not impair the activity of the catalyst. In an alternative embodiment, the stabilizer is used in a molar amount which essentially does not impair the activity of the catalyst. A molar ratio of the stabilizer to the catalyst of 10,000: 1 to 1: 1, preferably 1,000: 1 to 10: 1, more preferably 250: 1 to 20: 1, most preferably 100: 1 to 50: 1, is preferably used.

As already mentioned, an anti-oxidant is used as a stabilizer. The antioxidant usually works as a radical scavenger.

The antioxidant is selected from the group consisting of vitamin E, vitamin C (ascorbic acid), and combinations thereof.

According to the invention, vitamin E is used as a stabilizer. Vitamin E can be selected from the group consisting of α-tocopherol, β-tocopherol, γ-tocopherol, δ-tocopherol, α-tocotrienol, β-tocotrienol, γ-tocotrienol, δ-tocotrienol, α-tocomonoenol, β-tocomonoenol, γ-tocomonoenol, δ-tocomonoenol, salts thereof, and combinations thereof. Vitamin E is particularly preferably selected from the group consisting of α-tocopherol, γ-tocopherol, δ-tocopherol, salts thereof and combinations thereof. The use of α-tocopherol as a stabilizer is most preferred.
In a further suitable embodiment, the polyethylene is produced by means of a so-called coordination polymerization or coordinative insertion polymerization. This is understood to mean a polymerization of olefins on Lewis acidic metal complex compounds. A mixed catalyst comprising a precatalyst and a cocatalyst or activator is used as the catalyst.

A non-metallocene or non-metallocene is used as the precatalyst. Non-metallocenes are molecular catalysts that contain ligands other than metallocene catalysts. Preferred non-metallocenes are monocyclopentadienyl complexes, derivatives of monocyclopentadienyl complexes and a large number of complexes with one or more heteroatom donor ligands. Examples of suitable donor ligands are nitrogen- and / or oxygen-containing chelate ligands. In the case of the non-metallocene catalysts, the elements scandium, titanium, zirconium, hafnium, vanadium, niobium, chromium, molybdenum, tungsten, iron, cobalt, nickel, palladium, platinum and the lanthanides are possible as metal centers. According to the invention, chromium-containing non-metallocenes, in particular 2,3,4-trimethyl-1- (8-quinolyl) trimethyl-silyl-cycopentadienyl-chromium (III) chloride, are used.

Metallocene catalysts and non-metallocene catalysts are generally used as precatalysts in combination with a suitable cocatalyst or activator. According to the invention, the catalyst according to the invention is therefore a mixed catalyst comprising a non-metallocene as a precatalyst and a suitable cocatalyst or an activator. The cocatalyst or activator is an alkylaluminoxane, particularly preferably methylaluminoxane (MAO). Mixed catalysts are particularly suitable according to the invention, comprising chromium-based or chromium-containing non-metallocene catalysts (non-metallocene catalysts), in particular 2,3,4-trimethyl-1- (8-quinolyl) trimethyl-silyl-cycopentadienyl-chromium (III) chloride, as a precatalyst and methylaluminoxane (MAO) as a cocatalyst.

In a further embodiment, the catalyst is used in a concentration between 0.1 μmol and 400 μmol, in particular 1 μmol and 200 μmol, preferably 10 μmol and 100 μmol, based on 1 liter of a solvent or solvent mixture used for the polymerization. Preferably For the preparation of the catalyst, a molar ratio of a precatalyst to a methylaluminoxane cocatalyst (MAO cocatalyst) of 1:20 to 1: 20,000, preferably 1: 100 to 1: 5,000, more preferably 1: 200 to 1: 2,000, most preferably 1 : 500 to 1: 1,000, based on the aluminum atoms of the methylaluminoxane cocatalyst, used.

The polymerization of the ethylene is expediently carried out in a suitable reaction vessel, in particular in a Schlenk flask or polymerization reactor.

The polymerization is preferably carried out in a temperature range between 0 ° C and 120 ° C, in particular 20 ° C and 110 ° C, preferably 25 ° C and 100 ° C. Furthermore, the polymerization can be carried out at normal pressure or elevated pressure, in particular in an autoclave. The polymerization is preferably carried out at an excess pressure between 0.1 MPa and 10 MPa.

The polymerization can be carried out with particular advantage during a reaction time between 10 minutes and 240 minutes, in particular 10 minutes and 180 minutes, preferably 10 minutes and 60 minutes.

As a rule, the catalyst is destroyed after the polyethylene has been produced, for example by adding a methanol-hydrochloric acid mixture. If a solvent or solvent mixture is used, it is usually removed in a subsequent drying step, for example by applying a reduced pressure or vacuum, preferably a high vacuum. Alternatively or in combination with this, drying can be carried out in a drying cabinet.

In principle, polyethylene homopolymers or polyethylene copolymers can be produced with the aid of the process according to the invention. The production of a polyethylene homopolymer is preferred according to the invention. Thus, the method according to the invention can be used for producing a polyethylene which is selected from the group consisting of high density polyethylene (HDPE), low density polyethylene (LDPE) and high molecular weight polyethylene (HMWPE). The use of the process for the production of ultra-high molecular weight polyethylene (UHMWPE) is particularly preferred. The high molecular weight polyethylene (HMWPE) mentioned in this section preferably has a molecular weight between 10 ⁵ and 10 ⁶ g / mol. The ultra-high molecular weight polyethylene (UHMWPE) mentioned in this section preferably has a molecular weight between 10 ⁶ and 10 ⁷ g / mol.

If necessary, it can be provided in a further embodiment that the produced polyethylene doped with a stabilizer is crosslinked in a subsequent step. Crosslinking the polyethylene, especially ultra-high molecular weight polyethylene (UHMWPE), can significantly improve its abrasion behavior. The crosslinking can be carried out chemically or physically. The polyethylene can be chemically crosslinked, for example, by means of a peroxide treatment. Physical crosslinking of the polyethylene is preferably carried out by irradiation, in particular by ionizing irradiation. For example, the polyethylene can be crosslinked by treatment with γ-rays, β-rays, X-rays, ultraviolet rays, neutron rays, proton rays or electron rays.

In a further possible embodiment, the polyethylene doped with a stabilizer is subjected to heat treatment. On the one hand, the tempering can serve to reduce possible stresses in the polyethylene. This is especially true with regard to ultra-crosslinked high molecular weight polyethylene (UHMWPE). On the other hand, the mobility of any radicals that may be present in the polyethylene is increased by means of the tempering, which increases their recombination probability and their saturation by the stabilizer. As an alternative or in combination with this, the polyethylene can also be treated with microwaves or ultrasound waves in order to achieve increased radical saturation.

Finally, the present invention also relates to the use of a polyethylene, which is produced by a method according to the invention, for producing a medical device.

The medical-technical object is preferably designed as an implant, epithesis or orthosis. The medical-technical object is preferably selected from the group consisting of catheter, trocar, surgical suture material, hernia mesh, prolapse mesh or prolapse band, urinary incontinence band and prosthesis. The medical device is particularly preferably designed as a prosthesis, in particular an endoprosthesis. According to a further embodiment, the medical device is a joint prosthesis, preferably from the group consisting of hip joint prosthesis, knee joint prosthesis, ankle joint prosthesis, elbow joint prosthesis, temporomandibular joint prosthesis, shoulder joint prosthesis, Finger joint prosthesis and spinal joint surface prosthesis. In a further advantageous embodiment, the medical device is designed as a component, in particular in the form of a sliding surface, an insert or an insert, for a joint prosthesis. With regard to the joint prostheses in question, reference is made to the joint prostheses mentioned above. In particular, the medical device can be a prosthetic bearing component.

Further details and features of the invention emerge from the following description of preferred embodiments in the form of examples in combination with the subclaims. In these embodiments, individual features of the invention can be realized alone or in combination with other features. The preferred embodiments described are to be understood only as a descriptive disclosure and in no way as a disclosure that is limiting in any way.

Examples

General:

All experiments were carried out using the Schlenk technique and pre-dried argon as protective gas. Commercially available ethylene 3.0 was used as the polymerization gas without further purification. Toluene was obtained anhydrous and in 99.9% purity from Sigma-Aldrich and was further dried using a solvent drying apparatus from VAC to a water content of <5 ppm. The cocatalyst PMAO (polymethylene aluminooxane) was obtained from AKZO as a 7% solution in toluene. All other commercially available chemicals were used as received.

2,3,4-Trimethyl-1- (8-quinolyl) trimethylsilylcyclopentadienyl-chromium (III) chloride catalyst, abbreviated as CAT 1 in the following, was used as the precatalyst. Α-Tocopherol was used as vitamin E (purity> 96%, CAS No. 10191-41-0, Sigma-Aldrich).

Polymerization experiment 1

3.60 mg (8.38 × 10 ^-6 mol) of the precatalyst CAT 1 were dissolved in 10 ml of toluene in a 25 ml Schlenk flask. 100 ml of toluene were placed in a second 250 ml Schlenk flask and 0.31 g (7.17 × 10 ^-4 mol, corresponds to 85 eq. Based on CAT 1) of vitamin E were dissolved in it. The precatalyst CAT 1 was converted into the activated species with 3.23 g (8.38 × 10 ^-3 mol) PMAO (1000 eq Al, based on the catalyst) and added to the polymerization vessel with the aid of a syringe. Ethylene was passed in via the Schlenk connection and the reaction mixture was stirred at the highest level. The batch was cooled in a water bath. To terminate the polymerization, it was terminated with methanol / HCl. The reaction was terminated after just 13 minutes due to a sharp increase in viscosity in the flask caused by the precipitated polymer. The product obtained was washed in acetone for 2 hours and dried at 80 ° C. overnight.

Polymerization experiment 2

4.20 mg (9.78 × 10 ^-6 mol) of the precatalyst CAT 1 were dissolved in 10 ml of toluene in a 25 ml Schlenk flask. 100 ml of toluene were placed in a second 250 ml Schlenk flask and 0.86 g (1.99 × 10 ^-3 mol, corresponds to 205 eq. Based on CAT 1) of vitamin E were dissolved in it. The precatalyst CAT 1 was converted into the activated species with 3.77 g (9.78 × 10 ^-3 mol) PMAO (1000 eq Al, based on the catalyst) and added to the polymerization vessel with the aid of a syringe. Ethylene was passed in via the Schlenk connection and the reaction mixture was stirred at the highest level. The batch was stirred for a total of 3 hours, the batch being cooled with a water bath. To terminate the polymerization, it was terminated with methanol / HCl. The polymer obtained was washed in acetone for 2 hours and dried at 80 ° C. overnight.

Polymerization experiment 3 (not according to the invention)

7.70 mg (2.63 × 10 ^-5 mol) of the precatalyst zirconocene dichloride were dissolved in 10 ml of toluene in a 25 ml Schlenk flask. 100 ml of toluene were placed in a second 250 ml Schlenk flask and 0.91 g (2.11 × 10 ^-3 mol, corresponds to 80 eq. Based on zirconocene dichloride) of vitamin E were dissolved in it. The precatalyst zirconocene dichloride was converted into the activated species with 10.15 g (2.63 × 10 ^-2 mol) PMAO (1000 eq Al, based on the catalyst) and added to the polymerization vessel with the aid of a syringe. Ethylene was passed in via the Schlenk connection and the reaction mixture was stirred at the highest level. The reaction was run for a total of 20 minutes, the batch being cooled with a water bath. To terminate the polymerization, it was terminated with methanol / HCl. The polymer obtained was washed in acetone for 2 hours and dried at 80 ° C. overnight.

The polymers obtained after carrying out the polymerization experiments described above were colored, which confirmed the incorporation of vitamin E into the polymers or the doping of the polymers with vitamin E.

The results obtained are summarized in Table 1 below, with experiments K1 and K2 denoting control experiments without a stabilizer. Table 1: Data from the polymerization experiments attempt used catalyst Additive Mw [10 ⁶ ] Activity [g / mmol h] Yield [g] Polym. Time [min] PDI [Mw / Mn] The internal term 1 CAT 1 Vitamin E (85eq) 1.58 1651 3.00 13th 6.70 130 2 CAT 1 Vitamin E (205eq) 3.93 about 130 4.15 about 180 2.76 131 3 ZrCp ₂ Cl ₂ Vitamin E (80eq) 0.50 350 3.01 20th 3.38 138 K1 CAT 1 - 0.247 2550 - - 2.7 - K2 ZrCp ₂ Cl ₂ - 0.61 2330 - - - -

Summary

Overall, the experiments described above show that, on the one hand, the synthesis of polyethylene is possible in the presence of an antioxidant. In the case of the chromium-based catalyst used, the catalytic activity is only slightly reduced by the presence of the antioxidant, so that technical implementation is easily possible. In the case of the ZrCp ₂ Cl ₂ catalyst, there is a more pronounced loss of activity. However, the remaining activity is still sufficient to be able to operate satisfactory catalysis with it. The experiments also show that the production of polyethylene doped with an antioxidant is possible under generally gentle reaction conditions. A particular advantage relates to the considerably shortened reaction time compared to the processes known from the prior art. The molecular weight of the polymers produced was approx. 1.6 × 10 ⁶ mol / g.

Claims (15)

Process for the production of a polyethylene doped with a stabilizer, wherein a polymerization of ethylene is carried out in the presence of a stabilizer and a catalyst, characterized in that an antioxidant from the group consisting of vitamin E, vitamin C and combinations thereof and as a catalyst a Mixed catalyst comprising a precatalyst and a cocatalyst is used, a chromium-containing non-metallocene being used as the precatalyst and an alkylaluminoxane being used as the cocatalyst and the ethylene being passed into a solution containing the stabilizer, the catalyst and a solvent or solvent mixture for the polymerization becomes. Procedure according to Claim 1 , characterized in that to prepare the solution, first the catalyst and then the stabilizer are dissolved in the solvent or solvent mixture. Procedure according to Claim 1 or 2 , characterized in that the stabilizer essentially does not impair the activity of the catalyst or the stabilizer is used in a molar amount which essentially does not impair the activity of the catalyst. Process according to one of the preceding claims, characterized in that a molar ratio of the stabilizer to the catalyst of 10,000: 1 to 1: 1, preferably 1000: 1 to 10: 1, more preferably 250: 1 to 20: 1, most preferably 100: 1 to 50: 1 is used. Method according to one of the preceding claims, characterized in that the vitamin E is selected from the group consisting of α-tocopherol, β-tocopherol, γ-tocopherol, δ-tocopherol, salts thereof and combinations thereof. Process according to one of the preceding claims, characterized in that 2,3,4-trimethyl-1- (8-quinolyl) trimethyl-silyl-cycopentadienyl-chromium (III) chloride is used as the precatalyst and methylaluminoxane (MAO) is used as the cocatalyst. Process according to one of the preceding claims, characterized in that the catalyst is used in a concentration between 0.1 µmol and 400 µmol, in particular 1 µmol and 200 µmol, preferably 10 µmol and 100 µmol, based on 1 liter of a solvent used for the polymerization or Solvent mixture is used. Process according to one of the preceding claims, characterized in that a molar ratio of a precatalyst to a methylaluminoxane cocatalyst of 1:20 to 1: 20,000, preferably 1: 100 to 1: 5,000, more preferably 1: 200 to 1: 2,000, most preferably 1: 500 to 1: 1,000, is used, based on the aluminum atoms of the methylaluminoxane cocatalyst. Process according to one of the preceding claims, characterized in that the polymerization is carried out in a temperature range between 0 ° C and 120 ° C, in particular 20 ° C and 110 ° C, preferably 25 ° C and 100 ° C. Process according to one of the preceding claims, characterized in that the polymerization is carried out at normal pressure or elevated pressure. Method according to one of the preceding claims, characterized in that the polymerization is carried out at an excess pressure between 0.1 MPa and 10 MPa. Process according to one of the preceding claims, characterized in that the polymerization is carried out for a reaction time between 10 min and 240 min, in particular 10 min and 180 min, preferably 10 min and 60 min. Use of a polyethylene, produced by a method according to one of the preceding claims, for producing a medical-technical object. Use after Claim 13 , characterized in that the medical object is designed as a prosthesis, in particular an endoprosthesis. Use after Claim 13 or 14th , characterized in that the medical object is designed as a joint prosthesis, in particular selected from the group consisting of hip joint prosthesis, knee joint prosthesis, ankle joint prosthesis, elbow joint prosthesis, temporomandibular joint prosthesis, shoulder joint prosthesis, finger joint prosthesis and spinal joint surface prosthesis.