CN106282664A - Biodegradable medical zinc lithium binary alloy material and preparation method and application - Google Patents

Abstract

The invention discloses a biodegradable medical zinc-lithium binary alloy material and its preparation method and application; the alloy material is composed of the following substances by weight percentage: lithium 0.55-10wt.%, the rest is Zn. The alloy obtained by smelting needs to be subjected to thermoplastic deformation processing before use, so as to refine the alloy structure and improve the performance of the alloy. The zinc alloy of the present invention has the advantages of excellent comprehensive mechanical properties, good biocompatibility, and controllable degradation rate, etc., and it can be used as a material for preparing degradable medical implant devices, and can be used in the preparation of intravascular stents and bone implants. , Maxillofacial surgery and craniocerebral surgery implants, surgical sutures, various surgical patches, staplers, vascular clips or nerve repair catheters, etc.

Description

Biodegradable medical zinc-lithium binary alloy material and its preparation method and application

technical field

The invention belongs to the field of biomedical materials, and in particular relates to a biodegradable medical zinc-lithium binary alloy material and a preparation method and application thereof.

Background technique

At present, the medical materials implanted into the human body are generally made of non-degradable metal materials, such as (1) austenitic stainless steel (316LSS); (2) cobalt-chromium alloy; (3) medical tantalum; (4) titanium and Its alloy; (5) nickel-titanium shape memory alloy. The application of these permanent implant materials has the following disadvantages, for example (1) after the permanent metal vascular stent is implanted into the human body, due to its non-degradability, there is a shortcoming of easily forming thrombus to cause restenosis and intimal fibrosis in the stent, and the stent It remains permanently in the body and cannot be taken out again. Once the blood vessel is blocked again at the same position, it becomes very difficult to implant another vascular stent; (2) After implanting stainless steel, titanium alloy bone nails, bone plates, etc. Afterwards, a second operation is required to remove it, which increases the pain and financial burden of the patient. Therefore, the research and development of biodegradable medical materials with good mechanical properties and biocompatibility has become an important development direction in this field.

At present, among degradable biomaterials, degradable polymer materials, bioceramics, magnesium-based alloys, and iron-based alloys are materials that have been studied in depth in recent years. However, due to the low strength of polymer materials and the poor plasticity of ceramic materials, their wide application in clinical practice is limited. Magnesium-based alloys have good biocompatibility, but their corrosion resistance is poor, and they are quickly degraded in the human body, losing their mechanical support. The corrosion rate of iron-based alloys is so slow that complete degradation can take years.

Zinc is one of the most basic essential trace elements for the human body. In the human body, zinc is involved in almost all physiological metabolic processes. In addition to catalytic or structural functions in various metalloenzymes, transcription factors and other proteins, zinc also performs its functions in the form of neurotransmitters or modulators. Zinc can promote cell renewal, enhance the body's immune ability, and maintain the growth and development of the body. Zinc deficiency may lead to disorders of all physiological functions of the human body. The zinc content in the adult body is 1.4-2.3g, and the dietary allowance for zinc for healthy adults is 15-40mg per day. Adults may have certain toxic reactions if they ingest about 300mg of zinc per day. Therefore, zinc alloy has good biocompatibility. The standard electrode potential of pure zinc is -0.763V, which is between pure magnesium (-2.37V) and pure iron (-0.44V), and the corrosion rate of zinc-based alloys is also between magnesium-based alloys and iron-based alloys. The degradation rate is the one that best meets the requirements of clinical implants.

However, the comprehensive mechanical properties of pure zinc are poor, and the corrosion rate is also slow, which is difficult to meet the needs of clinical medicine. Alloying pure zinc is the main method to improve its mechanical properties and corrosion rate. Fe, Li and trace elements Mg, Ca, Sr, Si, Mn and rare earth elements are added to zinc at the same time, but the strength and plasticity of the zinc alloy material prepared by this technology are low, and the performance of the ideal material for vascular stents is not yet achieved. Require. At the same time, it contains more alloying elements. On the one hand, more types of alloying elements are released during the degradation process, which increases the potential risk to the human body. On the other hand, the duplication of the alloy preparation process increases the difficulty of quality control of the material, and the corresponding alloy cost also increases. up. In our research, we found that the zinc-lithium binary alloy has higher strength and plasticity and a suitable degradation rate. At the same time, due to the simple material components, better biological safety, and simple melting and preparation process, it has more advantages as a medical implant material. .

Contents of the invention

Aiming at the deficiencies of existing medical degradable materials, the purpose of the present invention is to provide a biodegradable medical zinc-lithium binary alloy material with high strength, good plasticity, controllable degradation rate and biodegradability and its preparation method and application.

The purpose of the present invention is to realize through the following technical solutions:

In the first aspect, the present invention relates to a biodegradable medical zinc-lithium binary alloy material. The alloy material includes the following components in weight percentage: 0.55-10% lithium and 90-99.45% zinc.

Preferably, the alloy material includes the following components in weight percentage: 1-3% lithium, 97-99% zinc, or 4.1-10% lithium, 90-95.9% zinc. Most preferably lithium 1-3%, zinc 97-99%.

In a second aspect, the present invention also relates to a method for preparing the aforementioned biodegradable medical zinc-lithium binary alloy material, the method comprising the following steps:

S1, weighing zinc raw material and lithium raw material according to the alloy ratio;

S2, heating and melting the zinc raw material, the mixed flux, and the lithium raw material, and stirring evenly to form an alloy melt;

S3. The alloy melt is refined, left to stand, poured and then cooled to obtain a biodegradable medical zinc-lithium binary alloy ingot material.

Preferably, the zinc raw material is pure zinc, and the lithium raw material is pure lithium; step S2 specifically includes: first heating pure zinc (purity ≥ 99.995%) to 420°C-440°C until it is completely melted, and then melting the molten When the temperature rises to 580-620°C, add mixed flux, wait until the mixed flux completely covers the surface of the melt while reducing the melt temperature to 540-560°C, add pure lithium (purity ≥ 99.999%) under the protection of Ar gas.

Preferably, in step S1, the zinc raw material is pure zinc, and the lithium raw material is pure lithium; according to the alloy ratio, it is specifically weighed: pure lithium is calculated at a yield of 80-85%, and other alloys (Zn ) elements are calculated on the basis of 100% yield.

Preferably, the mixed flux is a mixed flux of LiCl and LiF. More preferably, the mass ratio of LiCl and LiF in the mixed flux of LiCl and LiF is 1:2-4.

Preferably, the amount of the mixed flux is such that the thickness covered on the surface of the melt is 5-10 mm.

Preferably, in step S3, the refining is carried out with hexachloroethane, the refining temperature is 540±20° C., and the amount of hexachloroethane is 0.2-0.3% of the total weight of the alloy melt.

Preferably, it also includes homogenizing the alloy ingot material obtained in step S3, and performing hot extrusion or rolling deformation processing.

Preferably, the homogenization treatment temperature is 320-380°C, and the treatment time is 4-10 hours; the deformation temperature of the hot extrusion process is 190-280°C, and the extrusion ratio is 6-50:1; the rolling The deformation temperature of the deformation processing is 190-280°C, and the rolling amount per pass is 10-30%; the hot extrusion or rolling deformation is water-cooled or air-cooled to obtain a biodegradable medical zinc-lithium binary alloy plastic deformation processing state material.

Preferably, after step S3, it may also include further preparing the alloy ingot material into a three-dimensional interconnected tissue engineering scaffold through a casting process, and processing the alloy deformed material into a wire material and a capillary tube material for the bracket through a combined extrusion, rolling and drawing process A step of.

In the third aspect, the present invention also relates to the use of the aforementioned biodegradable medical zinc-lithium binary alloy material in the preparation of degradable medical implant devices.

Preferably, the degradable medical implant device is an implant stent, intraosseous implant, implant device for maxillofacial surgery and craniocerebral surgery, surgical suture, various surgical patches, stapler, vascular clip or nerve repair Catheter; the implanted stent includes vascular stent, bile duct stent, tracheal stent, urethral stent, esophageal stent or intestinal stent; the bone implant includes bone plate, bone nail, internal fixation screw, intramedullary needle or bone tissue engineering stand.

Preferably, the patch includes a patch for intestinal surgery or a patch for craniocerebral surgery; the stapler includes an intestinal stapler and a blood vessel stapler.

The invention greatly improves the mechanical properties of the alloy by adding a certain amount of Li element into the matrix Zn, and at the same time can adjust the corrosion degradation rate of the zinc alloy in the biological environment.

Compared with the prior art, the present invention has the following beneficial effects:

1. The zinc-lithium binary alloy of the present invention can be naturally degraded in the human body, and after achieving medical effects, it will degrade and disappear from the body within a certain period of time, and finally be safely excreted through metabolism.

2. The zinc alloy of the present invention uses lithium as the main alloying element, which can significantly improve the strength and plasticity of the zinc-lithium binary alloy. The highest tensile breaking strength reaches 501MPa, and the tensile elongation reaches 48%. Moreover, the adjustment of strength and plasticity can be realized by controlling the content of Li element (0.55-10wt.%, more preferably 1%-3% and 4.1-10%, most preferably 1.0-3wt.%).

3. The zinc alloy of the present invention has good mechanical properties, corrosion resistance and biocompatibility. According to the requirements of different uses for material properties, the corresponding mechanical properties and corrosion resistance can be obtained by properly adjusting the content of Li element. If the content of Li element is properly reduced, a medium-strength, high-plasticity and corrosion-resistant material can be obtained, which is suitable for drawing into wires and capillary tubes for vascular stents; if the content of Li element is appropriately increased, the corrosion rate will increase accordingly, and high strength can be obtained. Moderately plastic material, suitable for use as bone implant material.

4. Similar to the zinc element, the lithium element itself in the Zn-Li alloy in the present invention is also one of the essential trace elements for the human body; the effect of lithium on the central nervous system of the human body is obvious, and lithium salts are effective for improving and stabilizing emotions and preventing Schizophrenia is effective and it also improves the positive symptoms of schizophrenia such as hallucinations and delusions. Lithium salts such as lithium carbonate, lithium sulfate, and lithium glutamate are used in medicine to control and treat mania. Li ⁺ ions have a preventive effect on the incidence of atherosclerosis. Normal people's dietary requirement for lithium is about 60-100 μg/d, and lithium intake lower than 25 μg/d will have adverse effects.

5. The zinc-lithium binary alloy of the present invention has simple composition, simple alloy preparation process, and convenient material quality control. At the same time, the corrosion degradation product has fewer ion types, less potential harm to the human body, and has better biocompatibility compared with the prior art.

detailed description

The present invention will be described in detail below in conjunction with specific embodiments. The following examples will help those skilled in the art to further understand the present invention, but do not limit the present invention in any form. It should be noted that those skilled in the art can make several modifications and improvements without departing from the concept of the present invention. These all belong to the protection scope of the present invention.

Example 1

This embodiment relates to a degradable medical Zn-Li alloy material, which includes the following alloy components in weight percentage: Li is 0.55%, and the rest is Zn.

The preparation steps of the alloy material are as follows:

S1. Weigh each raw material according to the above alloy ratio;

S2. Put pure zinc (purity ≥ 99.995%) into an iron crucible with a protective coating on the inner wall, raise the temperature to 420°C and wait for the pure zinc to completely melt, then raise the temperature of the zinc melt to 580°C, then add LiCl and LiF Mix flux (mass ratio is 1: 3), after the above-mentioned mixed solvent completely covers the surface of zinc melt, then lower the temperature of zinc melt to 540°C, at this time add pure lithium (purity ≥ 99.999% ), after the pure lithium is melted, stir evenly to form an alloy melt;

S3. Refining the alloy melt with hexachloroethane, the refining temperature is 540±5°C, and the amount of hexachloroethane is 0.25% of the total weight of the alloy melt; after the refining is completed, stand at 540±5°C 12 minutes, cooling after pouring, to obtain biodegradable medical zinc-lithium binary alloy ingot material;

S4. Perform homogenization treatment on the obtained alloy ingot material, as well as hot extrusion or rolling deformation processing, to the biodegradable medical zinc-lithium binary alloy plastic deformation processing state material; wherein, the homogenization treatment temperature is 350 ℃, treatment time 8h; hot extrusion or rolling processing deformation temperature is 250 ℃, extrusion ratio is 28:1 or 20% of the rolling amount per pass, water cooling after extrusion or rolling deformation.

Example 2

This embodiment relates to a degradable medical Zn-Li alloy material, which includes the following alloy components in weight percentage: Li is 10%, and the rest is Zn.

The preparation method of this alloy material is the same as embodiment 1, and difference is:

S2. Put in pure zinc and raise the temperature to 430°C. After the pure zinc is completely melted, raise the temperature of the zinc melt to 600°C. At this time, add LiCl and LiF mixed flux (mass ratio: 1:3), until the above mixed solvent is completely covered After the surface of the zinc melt is removed, the temperature of the zinc melt is lowered to 550°C, and then pure lithium is added under the protection of Ar gas;

s3. The refining temperature is 540±10°C, and the amount of hexachloroethane is 0.2% of the total weight of the alloy melt; after refining, stand still at 540±10°C for 10 minutes;

S4. The homogenization treatment temperature is 320°C, and the treatment time is 10 hours; the deformation temperature of hot extrusion or rolling is 190°C, and the extrusion ratio is 50:1 or the rolling amount per pass is 30%.

Example 3

This embodiment relates to a degradable medical Zn-Li alloy material, which includes the following alloy components in weight percentage: Li is 4.1%, and the rest is Zn.

The preparation method of this alloy material is the same as embodiment 1, and difference is:

S2. Put in pure zinc and raise the temperature to 440°C. After the pure zinc is completely melted, raise the temperature of the zinc melt to 590°C. At this time, add LiCl and LiF mixed flux (mass ratio: 1:3), until the above mixed solvent is completely covered After the surface of the zinc melt is removed, the temperature of the zinc melt is lowered to 560°C, and then pure lithium is added under the protection of Ar gas;

S3. The refining temperature is 540±10°C, and the amount of hexachloroethane is 0.3% of the total weight of the alloy melt; after refining, stand still at 540±10°C for 15 minutes;

S4. The homogenization treatment temperature is 380° C., and the treatment time is 6 hours; the deformation temperature of hot extrusion or rolling is 250° C., and the extrusion ratio is 6:1 or the rolling amount per pass is 10%.

Example 4

This embodiment relates to a degradable medical Zn-Li alloy material, which includes the following alloy components in weight percentage: Li is 1.0%, and the rest is Zn.

The preparation method of this alloy material is the same as embodiment 1, and difference is:

S2. Put in pure zinc and raise the temperature to 440°C. After the pure zinc is completely melted, raise the temperature of the zinc melt to 620°C. At this time, add LiCl and LiF mixed flux (mass ratio: 1:3), until the above mixed solvent is completely covered After the surface of the zinc melt is removed, the temperature of the zinc melt is lowered to 560°C, and then pure lithium is added under the protection of Ar gas;

S3. The refining temperature is 550±10°C, and the amount of hexachloroethane is 0.3% of the total weight of the alloy melt; after refining, stand still at 550±10°C for 15 minutes;

S4. The homogenization treatment temperature is 380° C., and the treatment time is 6 hours; the deformation temperature of hot extrusion or rolling is 280° C., and the extrusion ratio is 6:1 or the rolling amount per pass is 10%.

Example 5

This embodiment relates to a degradable medical Zn-Li alloy material, which includes the following alloy components in weight percentage: Li is 2.0%, and the rest is Zn.

The preparation method of this alloy material is the same as embodiment 1, and difference is:

S2. Put in pure zinc and raise the temperature to 435°C. After the pure zinc is completely melted, raise the temperature of the zinc melt to 600°C. At this time, add LiCl and LiF mixed flux (mass ratio: 1:3), until the above mixed solvent is completely covered After the surface of the zinc melt is removed, the temperature of the zinc melt is lowered to 560°C, and then pure lithium is added under the protection of Ar gas;

S3. The refining temperature is 550±10°C, and the amount of hexachloroethane is 0.3% of the total weight of the alloy melt; after refining, stand still at 550±10°C for 15 minutes;

S4. The homogenization treatment temperature is 380° C., and the treatment time is 6 hours; the deformation temperature of hot extrusion or rolling is 280° C., and the extrusion ratio is 6:1 or the rolling amount per pass is 10%.

Example 6

This embodiment relates to a degradable medical Zn-Li alloy material, which includes the following alloy components in weight percentage: Li is 3%, and the rest is Zn.

The preparation method of this alloy material is the same as embodiment 1, and difference is:

S2. Put in pure zinc and raise the temperature to 420°C. After the pure zinc is completely melted, raise the temperature of the zinc melt to 610°C. At this time, add LiCl and LiF mixed flux (mass ratio: 1:3), until the above mixed solvent is completely covered After the surface of the zinc melt is removed, the temperature of the zinc melt is lowered to 550°C, and then pure lithium is added under the protection of Ar gas;

S3. The refining temperature is 540±10°C, and the amount of hexachloroethane is 0.2% of the total weight of the alloy melt; after refining, stand still at 540±10°C for 13 minutes;

S4. The homogenization treatment temperature is 340° C., and the treatment time is 7 hours; the deformation temperature of hot extrusion or rolling is 220° C., and the extrusion ratio is 15:1 or the rolling amount per pass is 15%.

Example 7

With the Zn-Li alloy of the extruded deformed shape that embodiment 1～6 makes, carry out simulated body fluid (Hank's solution) immersion test, record the corrosion rate of Zn-Li binary zinc alloy as table 1:

Table 1

serial number Experimental Materials Corrosion rate (mm/y) 1 Example 1 0.12 2 Example 2 0.29 3 Example 3 0.21 4 Example 4 0.14 5 Example 5 0.16 6 Example 6 0.17

In this example, the in vitro degradation rate of Zn-Li binary zinc alloy was studied according to the ASTM-G31-72 standard test method, and it was found that the degradation rate of Zn-Li binary zinc alloy was slow in a simulated human body fluid environment at 37°C , and can be regulated by adjusting the content of Li element.

Example 8

Table 2 shows the tensile strength test results of the extrusion-deformed Zn-Li alloys prepared in Examples 1-6.

Table 2

In this example, according to the GB/T228.1-2010 test standard, the tensile mechanical properties of the Zn-Li binary zinc alloy examples 1 to 6 were tested, and the results are shown in Table 2. The study found that the highest yield strength of Zn-Li binary alloy is 501MPa, and the highest elongation at break is 50%, which is much higher than that of Zn-Fe-Li zinc alloy (Zn 99.975%, Fe0.01%, Li 0.015%) yield strength 290MPa, elongation at break 36%. By rationally adding the content of Li element (0.55-10wt.%, most preferably 1.0-3wt.%), zinc alloys with different strengths and plasticity can be obtained to meet the performance requirements of different medical degradable materials for zinc alloys.

Example 7

The in vitro cytotoxicity test was carried out with the Zn-Li alloys prepared in Examples 1-6.

In this example, according to GB/T 16886.5-2003, the in vitro cell (L-929 fibroblast) toxicity test was carried out on zinc alloy, and the above-mentioned zinc alloy degradation product had no obvious influence on cell activity, and the cytotoxicity was grade 1, showing excellent cell compatibility.

Example 8

For the Zn-Li alloy materials described in the above embodiments 1-6, the Zn-Li ingot material can be further prepared into a three-dimensional Unicom tissue engineering scaffold through a conventional casting process; Deformable materials are processed into wires and capillary tubes for scaffolds. Therefore, it can be further prepared into a biodegradable medical implant device. The degradable medical implant devices include implant brackets, intraosseous implants, implant devices for maxillofacial surgery and craniocerebral surgery, surgical sutures, various surgical patches, staplers, vascular clips, or nerve repair catheters. The implanted stents include vascular stents, bile duct stents, tracheal stents, urethral stents, esophageal stents or intestinal stents; intraosseous plant devices include bone plates, bone nails, internal fixation screws, intramedullary nails or bone tissue engineering stents; The patches include intestinal surgery patches and brain surgery patches; staplers include intestinal staplers, blood vessel staplers, etc.

Specific embodiments of the present invention have been described above. It should be understood that the present invention is not limited to the above-mentioned specific embodiments, and those skilled in the art can make various deformations or modifications without departing from the concept of the present invention, which does not affect the essence of the present invention, and should be Be deemed to belong to the protection scope of the present invention.

Claims (10)

1. A biodegradable medical zinc-lithium binary alloy material, characterized in that the alloy material comprises the following components in weight percent: lithium 0.55-10%, zinc 90-99.45%. 2. a preparation method of biodegradable medical zinc-lithium binary alloy material as claimed in claim 1, is characterized in that, described method comprises the following steps: S1, weighing zinc raw material and lithium raw material according to the alloy ratio; s2, heating and melting the zinc raw material, mixed flux, and lithium raw material, and stirring evenly to form an alloy melt; S3. The alloy melt is refined, left to stand, poured and then cooled to obtain a biodegradable medical zinc-lithium binary alloy ingot material. 3. The method for preparing a biodegradable medical zinc-lithium binary alloy material according to claim 2, characterized in that step S2 is specifically: heating pure zinc to 420°C to 440°C for insulation and melting, and waiting for the melt temperature to When the temperature rises to 580-620°C, add the mixed flux. After the mixed flux completely covers the surface of the melt, reduce the temperature of the melt to 540-560°C, and then add pure lithium under the protection of Ar gas. 4. The preparation method of the biodegradable medical zinc-lithium binary alloy material according to claim 3, wherein the mixed flux is a mixed flux of LiCl and LiF. 5. The preparation method of biodegradable medical zinc-lithium binary alloy material according to claim 3, characterized in that, in step s3, the refining is carried out with hexachloroethane, and the refining temperature is 540±20°C, The amount of hexachloroethane is 0.2-0.3% of the total weight of the alloy melt. 6. The preparation method of the biodegradable medical zinc-lithium binary alloy material according to claim 3, further comprising homogenizing the alloy ingot material obtained in step S3, and hot extrusion or rolling Processing of deformation processing. 7. The preparation method of biodegradable medical zinc-lithium binary alloy material according to claim 6, characterized in that, the homogenization treatment temperature is 320-380°C, and the treatment time is 4-10h; the hot extrusion The deformation temperature of the processing is 190-280°C, and the extrusion ratio is 6-50:1; the deformation temperature of the rolling deformation processing is 190-280°C, and the rolling amount per pass is 10-30%; the heat After water cooling or air cooling after extrusion or rolling deformation, a biodegradable medical zinc-lithium binary alloy plastically deformed processed state material is obtained. 8. The method for preparing the biodegradable medical zinc-lithium binary alloy material according to any one of claims 2 to 7, characterized in that, after step S3, further preparation of the alloy ingot material by casting process A three-dimensional interconnected tissue engineering scaffold is formed, and the alloy deformed material is processed into a wire material and a capillary tube material for the scaffold through a combination process of extrusion, rolling and drawing. 9. A use of the biodegradable medical zinc-lithium binary alloy material as claimed in claim 1 in the preparation of degradable medical implant devices. 10. The use according to claim 9, characterized in that: the degradable medical implant device is an implant bracket, intraosseous implant, maxillofacial surgery and craniocerebral surgery implant device, surgical suture, various surgical Use patches, staplers, vascular clips or nerve repair catheters; the implanted stents include vascular stents, bile duct stents, tracheal stents, urethral stents, esophagus stents or intestinal stents; the bone implants include bone plates, bone screws , internal fixation screws, intramedullary nails or bone tissue engineering scaffolds.