A method for processing a sample of a polymer material implanted in the body

Abstract

The present invention provides a method for processing a sample of a high-molecular material implanted in the body. The method comprises the following steps: soaking a high-molecular matrix material in a nitrate solution containing metal ions at a temperature of 40-50 °C for more than 10 h, and then coating a film on the surface after soaking. The metal ions include any one or several of yttrium, tantalum, zirconium, silver, and strontium metal elements, and the high-molecular matrix material at least includes an alloy; the film coating includes an innermost pure titanium layer, a middle pure tantalum layer, and an outermost tantalum-yttrium alternating layer. The method for processing a sample of a high-molecular material implanted in the body according to the present invention improves the biocompatibility, antibacterial property, and fundamentally improves the stability of the material itself by soaking in a solution containing metal ions and coating a film.

Description

Technical Field

[0001] The present invention relates to the field of applications of materials implanted in the body, and more particularly, to a method for processing samples of high-molecular materials implanted in the body. Background Art

[0002] High-molecular materials implanted in the body can be widely used in multiple aspects such as artificial blood vessels, artificial bones and joints, and surgical sutures. The scope of high-molecular materials implanted in the body itself is also relatively wide. For example, bio-inert high-molecular materials, common materials include: polyethylene, polypropylene, polyacrylate, aromatic polyester, polysulfone, polytetrafluoroethylene (PTFE), silicone rubber, polyurethane (PU), polyetheretherketone (PEEK), polyvinyl chloride (PVC), polystyrene (PS), etc. Another example is biodegradable high-molecular materials, including: collagen, aliphatic polyester, chitin, cellulose, polyamino acid, polyvinyl alcohol, polylactic acid (PLA), polycaprolactone (PCL), etc.

[0003] However, in the process of using the above materials, there are often problems such as insufficient biocompatibility, stability, and antibacterial properties, which will directly limit the application of the above materials.

[0004] In view of this, the present invention is specifically proposed. Summary of the Invention

[0005] The first object of the present invention is to provide a method for processing samples of high-molecular materials implanted in the body. By soaking with a solution containing metal ions and covering with a film, the biocompatibility, antibacterial property of the material itself are improved, and the stability of the material itself is fundamentally improved.

[0006] In order to achieve the above object of the present invention, the following technical solutions are specifically adopted:

[0007] The present invention provides a method for processing samples of high-molecular materials implanted in the body, including the following steps:

[0008] Soak the high-molecular matrix material in a nitrate solution containing metal ions at a temperature of 40 - 50 °C for more than 10 hours, and then cover the surface with a film. The metal ions include any one or more of yttrium, tantalum, zirconium, silver, and strontium metal elements, and the high-molecular matrix material includes at least an alloy;

[0009] The film covering includes an innermost pure titanium layer, an intermediate pure tantalum layer, and an outermost tantalum-yttrium alternating layer.

[0010] In the solution of the present invention, if the matrix material only contains polymer materials, it is not applicable to the solution of the present invention. The matrix material needs to have a certain alloy composition, because in this way, the hardness and support degree of the matrix are sufficient to carry out the subsequent soaking and film coating processes and ensure the smooth progress of the subsequent processes.

[0011] During the soaking process, a metal ion solution containing any one or more of the metal elements of yttrium, tantalum, zirconium, silver, and strontium is selected because each of the above metals plays a crucial role in the better combination of the implant and the human body. Tantalum itself has good corrosion resistance and good toughness. Silver has good antibacterial properties, which can improve the fusion degree of the implant in the body and reduce the risk of bacterial infection. The addition of yttrium, zirconium, and strontium metals can cooperate with tantalum to improve the toughness of the material itself, reduce rejection, promote the fusion of the human body and the implant, and improve the tissue regeneration of the human body itself. In the selection process of the above metal elements, in addition to considering the possibility of mutual compatibility, the improvement of the performance of the material itself is also considered. Because the requirements for antibacterial and anti-pollution properties of the implant material are extremely high, careful selection is required when choosing metal ions. It is necessary to select metals that are beneficial to the human body and can reduce the rejection reaction, and also consider the improvement of the performance of the material itself after mutual cooperation.

[0012] Preferably, as a further feasible solution, the composition of the metal ions includes: by mass, 1-5 parts of yttrium, 0.5-2 parts of tantalum, 5-10 parts of zirconium, 1-3 parts of silver, and 0.5-1 part of strontium.

[0013] Preferably, as a further feasible solution, by mass, 2-3 parts of yttrium, 1-1.5 parts of tantalum, 7-9 parts of zirconium, 2-2.5 parts of silver, and 0.7-0.9 part of strontium.

[0014] Preferably, as a further feasible solution, by mass, 2.5 parts of yttrium, 1.2 parts of tantalum, 8 parts of zirconium, 2.2 parts of silver, and 0.8 part of strontium.

[0015] In the above solution, a relatively better solution is that the metal ion solution contains nitrate solutions of yttrium, tantalum, zirconium, silver, and strontium at the same time. Because only when the above metal ions exist simultaneously can the complementary effect be achieved in terms of function. An even better solution is that the above metal ions are formulated in a certain mass ratio. In fact, although tantalum mainly improves the toughness of the material, silver mainly improves the antibacterial property of the material, and the addition of yttrium, zirconium, and strontium metals promotes biocompatibility, in actual functions, they also have an effect of mutual intersection and promotion. Because if the addition amount of silver itself is too large, it will be toxic, so it also relies on other metals such as yttrium to indirectly achieve the effect of co-antibacterial at the same time. At the same time, the addition of other metals can also further help the stability and toughness of the material itself to a certain extent. Therefore, in view of the fact that each metal ion does not play a single role in a certain aspect, it is more necessary to pay attention to the addition amount to ensure the mutual formulation relationship between each component.

[0016] Preferably, as a further feasible solution, the concentration of the nitrate solution is 20 - 30 wt%, and more preferably, it can also be 21 wt%, 22 wt%, 23 wt%, 24 wt%, 25 wt%, 26 wt%, 27 wt%, 28 wt%, 29 wt%, etc. The concentration of the soaking salt solution should not be too high, otherwise it will have a certain impact on the matrix material. The interaction between the metal ions and the matrix material after soaking can be promoted by means of micro-heating, and the soaking time can be appropriately extended to improve the effect.

[0017] Preferably, as a further feasible solution, the thickness ratio of the pure titanium layer, the pure tantalum layer, and the tantalum-yttrium alternating layer is 1:(2 - 3):(2 - 5).

[0018] Preferably, as a further feasible solution, the number of alternating layers of the tantalum-yttrium alternating layer is 3 - 8 layers, and the tantalum layer in the tantalum-yttrium alternating layer is adhered to the pure tantalum layer.

[0019] Preferably, as a further feasible solution, the thickness of the pure titanium layer is 0.05 - 0.08 μm, preferably 0.07 μm, and it can also be 0.06 μm, 0.075 μm, 0.055 μm, 0.065 μm, 0.075 μm, etc.

[0020] Preferably, as a further feasible solution, the content of tantalum pentoxide in the tantalum-yttrium alternating layer is 60 - 70 wt%, and the remainder is yttrium trioxide.

[0021] Preferably, as a further feasible solution, each layer of the coating film is sputter-coated with a corresponding target.

[0022] The purpose of coating the surface of the substrate after soaking is also to further improve a series of properties such as the biocompatibility and antibacterial properties of the implant material. In particular, by utilizing the effect of the formation of chemical bonds between various metal elements in the three-layer film, the film itself can be made more dense. In terms of the film structure, the pure titanium layer and the pure tantalum layer located in the inner layer play a role in corrosion resistance and stability improvement. The pure titanium layer is set in the innermost layer because titanium has better corrosion resistance than tantalum. Moreover, the outer layer is set as a tantalum-yttrium alternating layer to make the film layers containing tantalum adhere closely to each other, with stronger mutual forces. The setting method of the alternating layer can greatly improve the mutual filling effect compared to the single-layer film method, and the way of stacking layer by layer is also more conducive to the formation of grain structures between metal elements. Of course, considering the manufacturing cost of the entire specimen and its own performance, the number of alternating layers should not be too many. The number of alternating layers of the tantalum-yttrium alternating layer is 3 - 8 layers, and the corresponding number of layers will be selected according to the different mechanical properties of the substrate. In addition, in terms of the thickness ratio of each film layer, the pure titanium layer located in the innermost layer is laid relatively thinly because if the thickness is too thick, its ductility is poor and the bonding property with the substrate is not good. Then the two outer layers can be laid relatively thickly to improve the performance of metal elements in the film layer.

[0023] The reason why the content of tantalum is higher in the alternating layer is that yttrium oxide mainly plays an auxiliary role, so its content will be slightly lower.

[0024] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0025] (1) The method for processing the sample of the polymer implant material in the body of the present invention is very suitable for polymer implant materials containing certain alloy components in the substrate, and can achieve a series of properties such as improving the corrosion resistance, antibacterial property, and toughness of the material itself.

[0026] (2) During the processing of the polymer implant material in the body of the present invention, soaking is carried out using a solution containing various metal ions, fully considering the possibility of the mutual compatibility of various metal elements and also fully considering the improvement of the material's own performance.

[0027] (3) After soaking the polymer implant material in the body of the present invention, coating is carried out on the surface of the substrate, aiming to further improve a series of properties such as the biocompatibility and antibacterial property of the implant material. Specific embodiments

[0028] The embodiments of the present invention will be described in detail below in conjunction with examples. However, those skilled in the art will understand that the following examples are only used to illustrate the present invention and should not be regarded as limiting the scope of the present invention. For those not specified in the examples, they are carried out under conventional conditions or conditions recommended by the manufacturer. For reagents or instruments not specified for the manufacturer, they are all conventional products that can be obtained through commercial purchase.

[0029] Example 1

[0030] Step 1: Dissolve 1 g of yttrium nitrate, 2 g of tantalum nitrate, 5 g of zirconium nitrate, 3 g of silver nitrate, and 0.5 g of strontium nitrate in deionized water to prepare an aqueous nitrate solution containing yttrium, tantalum, zirconium, silver, and strontium ions. The solute concentration in the aqueous nitrate solution is controlled between 20 - 25 wt%.

[0031] Step 2: Select a bone replacement implant material formed by compounding TC4 titanium alloy and high molecular polyethylene as the substrate. Immerse the substrate in the aqueous nitrate solution formed in Step 1 above, heat it to 40 °C, soak for 10 h and simultaneously perform ultrasonic treatment. After treatment, take out the substrate and wipe it until the surface is completely dry.

[0032] Step 3: Then place the substrate on the sample stage in the workbench cavity, evacuate the cavity, and then introduce argon gas. After cleaning the substrate for 20 min, apply current to the titanium target to start the coating of the pure titanium layer. During the coating process, the workbench and the sample stage rotate, and the substrate rotates by itself. Among them, the rotation speed of the workbench is 1 r / min, the rotation speed of the sample stage is 20 r / min, and the rotation speed of the substrate is 10 r / min. The current on the titanium target is 10 - 15 A, and the coating time is 10 min to form a pure titanium layer on the surface of the substrate. The thickness of the pure titanium layer is 0.05 μm.

[0033] Step 4: Then apply a current of 10 - 15 A to the tantalum target, and the coating time is 20 min to form a pure tantalum layer outside the pure titanium layer, with a thickness of 0.1 μm.

[0034] Step 5: The sputtering of the alternating layer is carried out by alternately applying current to the tantalum target and the yttrium target. The formed alternating layer is 3 layers. First, use the tantalum target for sputtering to make it adhere to the pure tantalum layer. The coating time is 30 min, and the total thickness is 0.1 μm. The two tantalum layers are thicker than the yttrium layer to ensure that the content of tantalum pentoxide is 60 wt% and the content of yttrium trioxide is 40 wt%.

[0035] Step 6: After the coating is completed, stop applying current to the target, cool it down, and release the gas to obtain a product with a three-layer composite film coated on the surface of the substrate.

[0036] Example 2

[0037] Step 1: Dissolve 5 g of yttrium nitrate, 0.5 g of tantalum nitrate, 10 g of zirconium nitrate, 1 g of silver nitrate, and 1 g of strontium nitrate in deionized water to prepare an aqueous nitrate solution containing yttrium, tantalum, zirconium, silver, and strontium ions. The solute concentration in the aqueous nitrate solution is controlled between 25 - 30 wt%.

[0038] Step 2: Select a bone replacement implant material formed by compounding TC4 titanium alloy and high molecular polyethylene as the substrate. Immerse the substrate in the aqueous nitrate solution formed in Step 1 above, heat it to 50 °C, soak for 15 h and simultaneously perform ultrasonic treatment. After treatment, take out the substrate and wipe it until the surface is completely dry.

[0039] Step 3: Then place the substrate on the sample stage in the workbench cavity, evacuate the cavity, and then introduce argon gas. After cleaning the substrate for 20 min, apply electricity to the titanium target to start the coating of the pure titanium layer. During coating, the workbench and the sample stage rotate, and the substrate rotates by itself. Among them, the rotation speed of the workbench is 1 r / min, the rotation speed of the sample stage is 20 r / min, and the rotation speed of the substrate is 10 r / min. The current on the titanium target is 10 - 15 A, and the coating time is 12 min to form a pure titanium layer on the surface of the substrate. The thickness of the pure titanium layer is 0.06 μm.

[0040] Step 4: Then apply a current of 10 - 15 A to the tantalum target as well, and the coating time is 25 min to form a pure tantalum layer outside the pure titanium layer, with a thickness of 0.18 μm.

[0041] Step 5: The sputtering of the alternating layer is carried out by alternately applying current to the tantalum target and the yttrium target. The formed alternating layer is 8 layers. First, sputter with the tantalum target to make it adhere to the pure tantalum layer. The coating time is 35 min, and the total thickness is 0.3 μm. The thickness of the tantalum layer is thicker than that of the yttrium layer to ensure that the content of tantalum pentoxide is 70 wt% and the content of yttrium trioxide is 30 wt%.

[0042] Step 6: After coating is completed, stop applying current to the target, perform cooling and deflation to obtain a product with a three - layer composite film coated on the surface of the substrate.

[0043] Example 3

[0044] Step 1: Dissolve 2.5 g of yttrium nitrate, 1.2 g of tantalum nitrate, 8 g of zirconium nitrate, 2.2 g of silver nitrate, and 0.8 g of strontium nitrate in deionized water to prepare an aqueous nitrate solution containing yttrium, tantalum, zirconium, silver, and strontium ions. The solute concentration in the aqueous nitrate solution is controlled between 25 - 30 wt%.

[0045] Step 2: Select a bone replacement implant material formed by the composite of TC4 titanium alloy and high molecular polyethylene as the substrate, immerse the substrate in the nitrate aqueous solution formed in Step 1 above, heat it to 45 °C, soak for 15 h and simultaneously perform ultrasonic treatment. After the treatment, take out the substrate and wipe it until the surface is completely dry;

[0046] Step 3: Then place the substrate on the sample stage in the working table cavity, evacuate the cavity, and then introduce argon. After cleaning the substrate for 20 min, apply current to the titanium target to start the coating of the pure titanium layer. During the coating, the working table and the sample stage rotate, and the substrate rotates by itself. Among them, the rotation speed of the working table is 1 r / min, the rotation speed of the sample stage is 20 r / min, and the rotation speed of the substrate is 10 r / min. The current on the titanium target is 10 - 15 A, and the coating time is 15 min to form a pure titanium layer on the surface of the substrate, and the thickness of the pure titanium layer is 0.07 μm;

[0047] Step 4: Then apply a current of 10 - 15 A to the tantalum target, and the coating time is 25 min to form a pure tantalum layer outside the pure titanium layer, with a thickness of 0.18 μm;

[0048] Step 5: The sputtering of the alternating layer is carried out by alternately applying current to the tantalum target and the yttrium target. The formed alternating layer is 5 layers. First, sputter with the tantalum target to make it adhere to the pure tantalum layer. The coating time is 30 min, and the total thickness is 0.28 μm. The thickness of the tantalum layer is thicker than that of the yttrium layer to ensure that the content of tantalum pentoxide is 65 wt% and the content of yttrium trioxide is 35 wt%;

[0049] Step 6: After the coating is completed, stop applying current to the target, cool down and release the gas to obtain a product with a three - layer composite film coated on the surface of the substrate.

[0050] Example 4

[0051] The specific operation steps are the same as those in Example 3, except that: dissolve 2 g of yttrium nitrate, 1.5 g of tantalum nitrate, 7 g of zirconium nitrate, 2.5 g of silver nitrate, and 0.7 g of strontium nitrate in deionized water.

[0052] Example 5

[0053] The specific operation steps are the same as those in Example 3, except that: dissolve 3 g of yttrium nitrate, 1 g of tantalum nitrate, 9 g of zirconium nitrate, 2 g of silver nitrate, and 0.9 g of strontium nitrate in deionized water.

[0054] Example 6

[0055] The specific operation steps are the same as those in Example 3, except that: no yttrium is added.

[0056] Example 7

[0057] The specific operation steps are the same as those in Example 3, with the difference that: 6 g of yttrium nitrate, 1.2 g of tantalum nitrate, 8 g of zirconium nitrate, 0.5 g of silver nitrate, and 1.7 g of strontium nitrate are dissolved in deionized water.

[0058] Comparative Example 1

[0059] Other operation steps are the same as those in Example 3, with the difference that: the pure titanium layer located in the innermost layer is removed from the film.

[0060] Example 8

[0061] Other operation steps are the same as those in Example 3, with the difference that: the thickness of the pure titanium layer is 0.07 μm, and the thicknesses of the pure tantalum layer and the tantalum-yttrium alternating layer are also both 0.07 μm.

[0062] Example 9

[0063] Other operation steps are the same as those in Example 3, with the difference that: the formed alternating layer is 15 layers.

[0064] Example 10

[0065] Other operation steps are the same as those in Example 3, with the difference that: the content of tantalum pentoxide is 50 wt%, and the content of yttrium trioxide is 50 wt%.

[0066] Experimental Example 1

[0067] The properties of the final product materials made from the above examples and comparative examples were compared. Specifically, see Table 1 below. The bone replacement implant material formed by the composite of untreated TC4 titanium alloy and ultra-high molecular weight polyethylene was tested and its tensile strength was 737 MPa, and the yield strength was 850 MPa:

[0068] The antibacterial rate of Staphylococcus aureus was tested for Staphylococcus aureus according to the method in the national standard "Food Microbiology Examination - Examination of Staphylococcus aureus" (GB 4789.10 - 2016). The antibacterial rate of Escherichia coli was tested for Escherichia coli according to the method in the national standard "National Food Safety Standard - Food Microbiology Examination - Enumeration of Coliforms" (GB 4789.3 - 2010).

[0069] The corrosion rate was experimented under the condition of simulated body fluid, prepared with PBS (phosphate buffer solution), the pH was controlled at 7.4 to simulate the pH environment of the human body, the experimental temperature was set at 37 °C, the specimen was completely immersed in the prepared simulated body fluid, taken out after soaking for one week, and the corrosion rate was analyzed and recorded.

[0070]

[0071] As can be seen from Table 1 above, the implant material of the present invention has excellent toughness and strength, and good antibacterial properties, indicating that the bonding force between the matrix and the film is also strong. From the results of Example 6, it can be seen that without adding yttrium, it is impossible to make it cooperate better with other metals to achieve the effects of bonding, corrosion resistance, and antibacterial properties. Therefore, it can be seen that each component in the formula combination is indispensable.

[0072] From the results of Example 7, it can be seen that the addition amounts of yttrium nitrate and silver nitrate are larger than those in Example 3, while the addition amount of strontium nitrate is too small. The addition of strontium metal promotes biocompatibility. If the addition amount is insufficient, it will affect the stability of the material itself. At the same time, if the addition amounts of silver and yttrium are too large, the antibacterial and corrosion resistance properties of the material itself will be unbalanced, so it will affect the overall performance of the material itself. Therefore, from this example, it can be seen that each component needs to be controlled within a suitable proportion range.

[0073] From the data of Examples 8-9 and Comparative Example 1, it can be known that when the pure titanium layer is not added, or the thickness is inappropriate, or the number of alternating layers is too large, it will affect the performance of the material itself. Because the pure titanium layer mainly plays a role in corrosion resistance, its corrosion resistance effect is obvious, and it has a good effect on improving the performance of the sample after fitting with the matrix. Therefore, this layer is indispensable. Similarly, considering its different positions with the matrix in terms of thickness, its thickness also needs to be set differently. If it is set unreasonably, it will affect the bonding property. In addition, if the number of alternating layers is too large, it will also affect the operability and has no further effect on the performance improvement. Therefore, the number of alternating layers should not be too thick.

[0074] From the data of Example 10, it can be known that the contents of tantalum pentoxide and yttrium trioxide need to be properly proportioned according to the scheme of the present invention. Because in the process of the overall component formulation, yttrium trioxide mainly plays an auxiliary role, so its addition amount should not be too large, otherwise it will affect the overall performance of the sample.

[0075] Finally, it can be understood that the above embodiments are merely exemplary embodiments adopted to illustrate the principle of the present invention. However, the present invention is not limited thereto. For those of ordinary skill in the art, various modifications and improvements can be made without departing from the principle and essence of the present invention, and these modifications and improvements are also regarded as the protection scope of the present invention.

Claims

1. A method for processing polymer implant material samples, characterized in that: The steps include: The polymer matrix material is immersed in a nitrate solution containing metal ions at a temperature of 40-50° C. for more than 10 hours, and the surface is coated after the immersion, wherein the metal ions include any one or more of yttrium, tantalum, zirconium, silver, and strontium metal elements, and the polymer matrix material includes at least an alloy; The coating includes a pure titanium layer as an innermost layer, a pure tantalum layer as an intermediate layer, and a tantalum-yttrium alternating layer as an outermost layer; The composition of the metal ions includes: by mass, 1-5 parts of yttrium, 0.5-2 parts of tantalum, 5-10 parts of zirconium, 1-3 parts of silver, and 0.5-1 parts of strontium; the thickness ratio of the pure titanium layer, the pure tantalum layer, and the tantalum-yttrium alternating layer is 1:(2-3):(2-5), the number of alternating layers of the tantalum-yttrium alternating layer is 3-8 layers, wherein the tantalum layer in the tantalum-yttrium alternating layer is attached to the pure tantalum layer, the thickness of the pure titanium layer is 0.05-0.08μm, the content of tantalum pentoxide in the tantalum-yttrium alternating layer is 60-70wt%, and the rest is yttrium.

2. The method for processing polymer implant material samples according to claim 1, characterized in that: In terms of mass, the components include 2-3 parts of yttrium, 1-1.5 parts of tantalum, 7-9 parts of zirconium, 2-2.5 parts of silver, and 0.7-0.9 parts of strontium.

3. The method for processing polymer implant material samples according to claim 2, characterized in that: In terms of mass, there are 2.5 parts of yttrium, 1.2 parts of tantalum, 8 parts of zirconium, 2.2 parts of silver, and 0.8 parts of strontium.

4. The method for processing a polymer implant material sample according to any one of claims 1 to 3, characterized in that: The concentration of the nitrate solution is 20-30 wt%.

5. The method for processing polymer implant material samples according to claim 1, characterized in that: The thickness of the pure titanium layer is 0.07 μm.

6. The method for processing polymer implant material samples according to claim 1, characterized in that: The content of tantalum pentoxide in the tantalum-yttrium alternating layer is 60-70wt%, and the rest is yttrium.

7. The method for processing a polymer implant material sample according to any one of claims 1 to 6, characterized in that: Each layer of the coating is sputtered using a corresponding target material.

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