CN111073004B - Method for improving irradiation crosslinking density and oxidation stability of ultrahigh molecular weight polyethylene joint material - Google Patents

Abstract

The invention relates to a method for improving irradiation crosslinking density and oxidation stability of an ultrahigh molecular weight polyethylene joint material. The prepared artificial joint material consists of a plant phenolic acid antioxidant containing a double-bond structure and medical-grade ultrahigh molecular weight polyethylene, is prepared by compression molding and then irradiation crosslinking, and specifically comprises the following steps: the plant phenolic acid antioxidant containing a double-bond structure is doped with ultra-high molecular weight polyethylene; compression molding; and (4) performing irradiation crosslinking. The invention utilizes the double functional groups on the plant phenolic acid antioxidant containing the double bond structure, simultaneously improves the irradiation crosslinking density and the oxidation stability of the ultrahigh molecular weight polyethylene joint material, and is expected to improve the in vivo service life and the in vitro storage stability of the ultrahigh molecular weight polyethylene joint material.

Description

Improving Irradiation Crosslinking Density and Oxidation Stability of UHMWPE Joint Materials Methods

technical field

The invention belongs to the field of high-performance biomedical polymer materials, and specifically relates to a method for improving the irradiation crosslinking density and oxidation stability of ultra-high molecular weight polyethylene joint materials.

Background technique

Ultra-high molecular weight polyethylene (UHMWPE) has good mechanical properties, impact resistance, fatigue resistance, self-lubrication and biocompatibility, and is the preferred joint liner material to replace the knee meniscus and hip acetabular cartilage ( Kurtz SM, J Biomech Eng, 2006, 1(1), 107-123). However, during the long-term in vivo service, UHMWPE wears out continuously to produce wear debris, triggering host immune stress, severe inflammatory erosion and even tissue necrosis, requiring timely revision surgery (UrbanRM, J Bone Joint Surg Am 2000, 82(4), 457-476). Studies have shown that high-energy ray irradiation (such as X-rays and γ-rays) can make UHMWPE form a solid three-dimensional cross-linked network structure, which reduces the plastic deformation capacity of the material and significantly improves the wear resistance of the material (Muratoglu OK, Biomaterials, 2002, 23(3), 717-724). However, part of the radiation-induced free radicals are trapped in the crystal region, and combined with dissolved oxygen to undergo a chain oxidation reaction during the service period of the artificial prosthesis, which greatly deteriorates the wear resistance and mechanical properties of the material, and eventually leads to the failure of the prosthesis. (Costa L, Biomaterials, 1998, 19(15), 1371-1385).

(美国专利US6277390B1)。同年，全称(ASTM)公布了维生素E共混UHMWPE的标准规格，标志其在国际上得到广泛认可(ASTM F2695-07)。维生素E稳定UHMWPE的机理在于其分子结构上的酚羟基可提供质子氢猝灭自由基，从而阻断链式反应(Bracco P,PolymDegrad Stabil,2007,92(12),2155-62)。然而，由于VE使自由基快速灭活，阻碍了自由基相互间的交联反应，因此大幅降低UHMWPE辐照交联的效率。当维生素E的含量高于0.2wt％时，材料的交联密度无法随辐照剂量升高而增加，而力学性能也会受辐照计量升高而显著降低(Oral E,et al.Biomaterials 2008,29(26),3557-3560)。To eliminate residual free radicals, adding biocompatible antioxidants is a simple and convenient solution. Vitamin E (VE, also known as α-tocopherol) has been clinically verified to effectively improve the oxidation stability of irradiation crosslinked ultra-high molecular weight polyethylene artificial joint materials (US Patent US6448315B1, European Patent EP0995450B1). Represented by Ticnona, the vitamin E blended UHMWPE artificial joint material was first commercialized in 2007. The first-generation product name is

(US Patent US6277390B1). In the same year, the full name (ASTM) announced the standard specification of vitamin E blended UHMWPE, marking its wide recognition in the world (ASTM F2695-07). The mechanism of vitamin E stabilizing UHMWPE is that the phenolic hydroxyl group on its molecular structure can provide proton hydrogen to quench free radicals, thereby blocking the chain reaction (Bracco P, PolymDegrad Stabil, 2007, 92(12), 2155-62). However, because VE quickly inactivates free radicals and hinders the cross-linking reaction between free radicals, the efficiency of UHMWPE irradiation cross-linking is greatly reduced. When the content of vitamin E is higher than 0.2wt%, the crosslink density of the material cannot be increased with the increase of the irradiation dose, and the mechanical properties will be significantly reduced by the increase of the irradiation dose (Oral E, et al.Biomaterials 2008 , 29(26), 3557-3560).

In summary, although the antioxidant VE improves the oxidation resistance of UHMWPE, it hinders the cross-linking reaction of radiation-induced free radicals and limits the cross-linking density of the material. Obtaining ultra-high molecular weight polyethylene artificial joint materials with high irradiation crosslinking and high oxidation resistance has become the focus and difficulty of research and development.

Contents of the invention

Aiming at the deficiencies of the current technology, the purpose of the present invention is to provide a method for improving the irradiation crosslinking density and oxidation stability of ultra-high molecular weight polyethylene joint materials. A plant phenolic acid antioxidant containing a double bond structure is used to react with the ultra-high molecular weight polyethylene free radicals induced by irradiation to form a cross-linked network. At the same time, the phenolic hydroxyl groups on the plant phenolic acids donate hydrogen to eliminate residual free radicals, endowing the material with excellent oxidation stability. The prepared material has dual characteristics of high cross-linking and high anti-oxidation, which is beneficial to improving the long-term service life of the ultra-high molecular weight polyethylene artificial joint implant.

A method for improving the irradiation crosslinking density and oxidation stability of ultra-high molecular weight polyethylene joint materials provided by the present invention is to dope the ultra-high molecular weight polyethylene powder with plant phenolic acid antioxidants containing double bond structures, so that Materials that are radiation crosslinked after compression molding have high crosslink density and oxidation stability. The plant phenolic acid antioxidant containing a double bond structure is one of ferulic acid, hydroxycinnamic acid, rosmarinic acid or phenethyl caffeate. Compared with vitamin E, which only has monophenolic functional groups, the plant phenolic acid antioxidants with double bond structure can not only eliminate free radicals through the phenolic hydroxyl group, but also use radiation energy to stimulate the activity of double bonds. The free radicals of high molecular weight polyethylene form a cross-link network, which significantly increases the cross-link density of the material.

According to one embodiment of the method for improving the irradiation crosslinking density and oxidation stability of ultra-high molecular weight polyethylene joint material of the present invention, the preparation method of the material specifically includes the following steps:

A, plant phenolic acid antioxidant containing double bond structure doped with ultra-high molecular weight polyethylene: add ultra-high molecular weight polyethylene and plant phenolic acid antioxidant containing double bond structure in isopropanol and stir at high speed, the gained The mixture is vacuum-dried to obtain an antioxidant-doped powder;

B. Compression molding: placing the antioxidant-doped powder in a mold for compression molding, and then slowly cooling to room temperature for demoulding to obtain a molded blank;

C. Irradiation crosslinking: irradiating the vacuum-packed molded blank with high-energy rays at room temperature to obtain the ultra-high molecular weight polyethylene joint material.

According to one embodiment of the method for improving the irradiation crosslinking density and oxidation stability of ultra-high molecular weight polyethylene joint materials of the present invention, the plant phenolic acid antioxidant containing double bond structure is ferulic acid, hydroxycinnamic acid, rosemary A kind of phenethyl ester of aromatic acid or caffeic acid.

According to one embodiment of the method for improving the irradiation crosslinking density and oxidation stability of ultra-high molecular weight polyethylene joint materials of the present invention, the plant phenolic acid antioxidant containing double bond structure accounts for 0.1% to 1.0% of the total mass of oxygen agent.

According to an embodiment of the method for improving the irradiation crosslinking density and oxidation stability of ultra-high molecular weight polyethylene joint materials of the present invention, the ultra-high molecular weight polyethylene is of biomedical grade with a relative molecular mass of 5×10 ⁶ to 6×10 ⁶ g/mol, the density is 0.93~0.98g/cm ³ , and the particle diameter is 90~160μm.

According to an embodiment of the method for improving the irradiation crosslinking density and oxidation stability of ultra-high molecular weight polyethylene joint materials of the present invention, in step B, the molding temperature is 180-220°C, the molding pressure is 5-50 MPa, and the molding time is 2～8h.

According to an embodiment of the method for increasing the irradiation crosslinking density and oxidation stability of ultra-high molecular weight polyethylene joint materials of the present invention, in step C, the high-energy rays are electron beam rays or gamma rays, and the irradiation dose is 50-150 kGy.

Compared with the prior art, the present invention has significant advantages including:

(1) The present invention introduces the plant phenolic acid antioxidant containing double bond structure, under the premise of not adding other cross-linking agents, utilizes its own double bond to generate cross-linking reaction with ultra-high molecular weight polyethylene molecular chain, and improves The crosslink density of the material;

(2) The part of the plant phenolic acid antioxidant selected in the present invention has multiple phenolic hydroxyl groups, which can provide more antioxidant active sites than vitamin E containing monophenolic hydroxyl groups, and further improve the oxidation stability of materials;

(3) The ultra-high molecular weight polyethylene artificial joint material prepared by the present invention has the dual advantages of high cross-linking and high oxygen resistance, and can greatly improve the stability of the artificial joint material in vivo.

Description of drawings

Figure 1 shows the crosslink density of CAPE/UHMWPE and VE/UHMWPE at 150kGy irradiation dose.

Figure 2 shows the cross-link density of UHMWPE containing different types of antioxidants under the irradiation dose of 100 and 150kGy.

Figure 3 shows the oxidation induction time of UHMWPE containing different types of antioxidants under the irradiation dose of 150kGy.

Detailed ways

All features disclosed in this specification, or steps in all methods or processes disclosed, may be combined in any manner, except for mutually exclusive features and/or steps.

Any feature disclosed in this specification, unless specifically stated, can be replaced by other alternative features that are equivalent or have similar purposes. That is, unless expressly stated otherwise, each feature is one example only of a series of equivalent or similar features.

The method for increasing the irradiation crosslinking density and oxidation stability of the ultra-high molecular weight polyethylene joint material of the present invention will be described in detail below.

According to an exemplary embodiment of the present invention, the method for improving the irradiation crosslinking density and oxidation stability of ultra-high molecular weight polyethylene joint materials is to dope the ultra-high molecular weight polyethylene phenolic antioxidant containing double bond structure Polyethylene, the obtained antioxidant-doped powder is molded and cross-linked by radiation to obtain an artificial joint material of ultra-high molecular weight polyethylene with high cross-linking degree and oxidation stability.

That is to say, the present invention obtains a more excellent cross-linking effect than traditional radiation-crosslinked vitamin E-stabilized ultra-high molecular weight polyethylene by adding plant phenolic acid antioxidants containing a double bond structure to medical-grade ultra-high molecular weight polyethylene. density and oxidation resistance. The method improves the comprehensive performance of the ultra-high molecular weight polyethylene joint material, and is beneficial to prolonging the service time when it is implanted in the body.

Specifically, the preparation method of the present invention may include the following steps.

Step A: doping ultra-high molecular weight polyethylene with plant phenolic acid antioxidant containing double bond structure

Add ultra-high molecular weight polyethylene and plant phenolic acid antioxidant containing double bond structure to isopropanol and stir at high speed, vacuum dry the resulting mixture to obtain antioxidant doped powder; wherein, plant phenolic acid containing double bond structure The antioxidant accounts for 0.1% to 1.0% of the total mass of the ultra-high molecular weight polyethylene and the antioxidant.

According to the present invention, the selected ultra-high molecular weight polyethylene is biomedical grade, with a relative molecular mass of 5×10 ⁶ to 6×10 ⁶ g/mol, a density of 0.93 to 0.98 g/cm ³ , and a particle diameter of 90 to 160 μm .

According to the present invention, the selected plant phenolic acid antioxidant containing a double bond structure is one or more combinations of ferulic acid, hydroxycinnamic acid, rosmarinic acid or phenethyl caffeate.

Step B: Molding

The antioxidant-doped powder prepared in step A is placed in a mold for compression molding, and then slowly cooled to room temperature and demolded to obtain a molded blank.

In this step, the molding temperature is controlled to be 180-220° C., the molding pressure is 5-50 MPa, and the molding time is 2-6 hours to ensure a better pressing effect.

Step C: Molding

The ultra-high molecular weight polyethylene artificial joint material with high cross-linking degree and oxidation stability is prepared by radiating and cross-linking the vacuum-packed molded blank by high-energy rays.

In this step, the above-mentioned high-energy rays are electron beams or gamma rays, and the irradiation dose is 50-150 kGy.

The method for increasing the irradiation crosslinking density and oxidation stability of the ultra-high molecular weight polyethylene joint material of the present invention will be further described below in conjunction with specific examples and comparative examples.

Examples 1-12:

(1) Doping UHMWPE with plant phenolic acid antioxidants containing double bond structure: Add UHMWPE and plant phenolic acid antioxidants containing double bond structure to isopropanol and stir at high speed (plant phenolic acid species containing double bond structure See Table 1 for its proportion to the total mass, and see Table 2 for the name and structure of the antioxidant, and vacuum-dry the resulting mixture to obtain plant phenolic acid-doped powder.

(2) Compression molding: the obtained plant phenolic acid/UHMWPE powder is placed in a mold, molded at a temperature of 200° C. and a pressure of 10 MPa, then slowly cooled to room temperature, and the desired material is obtained after demoulding.

(3) Irradiation crosslinking: at room temperature, irradiate the vacuum-packed plant phenolic acid/UHMWPE molded blank with a 10 MeV electron beam, and the irradiation dose is shown in Table 1.

Comparative Examples 1-6:

(1) VE-doped UHMWPE: Add UHMWPE and VE to isopropanol (see Table 1 for the ratio of VE to the total mass of UHMWPE and VE, see Table 2 for the name and structure of antioxidants) and stir at high speed, and vacuum-dry the resulting mixture A VE doped powder is obtained.

(2) Compression molding: the above-mentioned VE/UHMWPE powder is placed in a mold, and the VE-doped UHMWPE powder is compression-molded at a temperature of 200° C. and a pressure of 10 MPa. Then slowly cool to room temperature, and get the billet after demoulding.

(3) Irradiation cross-linking: at room temperature, the vacuum-packed VE/UHMWPE molded blanks were irradiated with a 10 MeV electron beam, and the irradiation dose is shown in Table 1.

Formulation and irradiation conditions of table 1 embodiment 1-12 and comparative example 1-5

The full title, abbreviation, structural formula and structural feature of adding antioxidant in table 2 embodiment and comparative example

The crosslink density of each example and each comparative example was tested according to ASTM F2214. As shown in Figure 1, with the increase of the antioxidant concentration, the crosslink density of the comparative example decreased obviously when the antioxidant content was greater than 0.2%. When the mass fraction of anti-oxidation is 1.0%, the crosslinking density of the example is only 100mol/m ³ , indicating that VE significantly inhibits irradiation crosslinking at high concentrations. In stark contrast with it, the crosslinking density of embodiment is between 350-400mol/ ^m3 , is hardly affected by the change of antioxidant concentration, proves that the plant phenolic acid antioxidant containing double bond structure has the effect of promoting crosslinking ( Table 2, the double bond offsets the influence of part of the phenolic hydroxyl scavenging free radicals to inhibit the crosslinking); under the same antioxidant addition, the crosslinking density of the examples under different irradiation doses is greater than that of the comparative examples, and increases with the irradiation increased with increasing dose (Figure 2). Different types of plant phenolic acid antioxidants have little effect on the crosslink density, and the caffeic acid phenethyl ester obtained by esterifying caffeic acid has a better effect.

According to ISO11357-6:2002, the oxidation induction time of the material was tested by differential scanning calorimetry. Under the same antioxidant content, the material oxidation induction time of adding non-fat-soluble plant phenolic acid embodiment is equivalent to comparative example, and the material of adding caffeic acid phenethyl ester (embodiment 2) has better oxidation induction time, is Nearly 2 times that of other samples. It is proved that the plant phenolic acid with double bond structure can have better antioxidant performance by esterification modification method.

Based on the results of crosslink density and oxidation resistance, the use of traditional antioxidant vitamin E antioxidants inhibits radiation crosslinking at high concentrations, which is not conducive to the wear resistance of materials. The plant phenolic acid antioxidant with double bond structure not only has a group that can provide anti-oxidation function, but also has a double bond that promotes cross-linking reaction, which can greatly improve the wear resistance of the material while ensuring the oxidation resistance of the material.

In summary, the present invention proposes a method for improving the irradiation crosslinking density and oxidation stability of ultra-high molecular weight polyethylene joint materials. The plant phenolic acid antioxidant containing a double bond structure is used to replace vitamin E, and the cross-linking density of the material is greatly increased through the cross-linking reaction between its double bond and ultra-high molecular weight polyethylene free radicals. At the same time, the phenolic hydroxyl group as an antioxidant active group can still eliminate residual free radicals and maintain the stability of the material during use and storage in vivo.

Although the present invention has been described above in conjunction with exemplary embodiments, it should be clear to those skilled in the art that, without departing from the spirit and scope of the claims, various modifications and changes to the above embodiments also belong to the scope of this patent. protected range.

Claims (5)

1. A method for improving irradiation crosslinking density and oxidation stability of an ultrahigh molecular weight polyethylene joint material is characterized in that 0.1-1.0% of ferulic acid, hydroxycinnamic acid, rosmarinic acid or caffeic acid phenethyl ester plant phenolic acid antioxidant containing a double bond structure is doped in ultrahigh molecular weight polyethylene powder, and after compression molding and irradiation crosslinking, the composite material has high crosslinking density and high oxidation stability.

2. The method for improving the irradiation crosslinking density and the oxidation stability of the ultrahigh molecular weight polyethylene joint material according to claim 1, wherein the preparation method of the material specifically comprises the following steps:

A. the plant phenolic acid antioxidant containing a double-bond structure is doped with ultra-high molecular weight polyethylene: adding ultrahigh molecular weight polyethylene and a double-bond structure-containing plant phenolic acid antioxidant into isopropanol, stirring at a high speed, and vacuum drying the obtained mixture to obtain antioxidant-doped powder;

B. compression molding: placing the antioxidant doped powder in a die for compression molding, then slowly cooling to room temperature, and demolding to obtain a molded blank;

C. irradiation crosslinking: and (3) carrying out high-energy ray irradiation on the mould pressing blank packaged in vacuum at room temperature to obtain the ultrahigh molecular weight polyethylene joint material.

3. The method for improving the irradiation crosslinking density and the oxidation stability of the ultrahigh molecular weight polyethylene joint material according to claim 1 or 2, wherein the ultrahigh molecular weight polyethylene is biomedical grade and has a relative molecular mass of 5 x 10⁶～6×10⁶g/mol, density of 0.93-0.98 g/cm³The particle diameter is 90-160 μm.

4. The method for improving the irradiation crosslinking density and the oxidation stability of the ultrahigh molecular weight polyethylene joint material according to claim 2, wherein in the step B, the compression molding temperature is 180-220 ℃, the compression molding pressure is 5-50 MPa, and the compression molding time is 2-8 h.

5. The method for improving irradiation crosslinking density and oxidation stability of the ultrahigh molecular weight polyethylene joint material according to claim 2, wherein in step C, the high energy radiation is electron beam radiation or gamma radiation, and the irradiation dose is 50-150 kGy.

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