Abstract:
Degradable pure iron stent or iron alloy stent is provided. The stent is made containing 0.01 to 0.5 atom % of La, Ce or Sr. The stent is surface modified using ion implantation or plasma ion implantation to implant oxygen, nitrogen, La, Ce or Sr into the stent surface. The stent may also be manufactured by depositing a thin film of La, Ce, Sr, lanthana, ceria, strontia, iron or iron oxide onto the stent surface. The thickness of the deposited films is from 10 to 1000 nanometers with the grain size from 10 to 200 nanometers. The corrosion resistance of these stents is significantly increased, and the stents have good biocompatibility. The degradation of the stents is controllable. The stents can also provide sufficient support in blood vessel in 3-6 months after intervention and be degraded after 6 months.

Description:
CROSS REFERENCE TO RELATED PATENT APPLICATIONS 
       [0001]    This application is a National Stage Filing and claims priority to international patent application No.: PCT/CN2010/070905 to Nan Huang, Yongxiang Leng, Ping Yang, Hong Sun, Jin Wang, Yunying Chen, Guojiang Wan, Fengjuan Jing, Ansha Zhao, Kaiqin Xiong and Tianxue You filed on Mar. 8, 2010, which is incorporated by reference in its entirety. 
     
    
     FIELD OF THE INVENTION 
       [0002]    This present invention relates to biodegradable stents applied in treating vascular and brain blood vessel diseases. 
       BACKGROUND ART 
       [0003]    Percutaneous transluminal coronary angioplasty (PTCA) has been applied in clinic since 1977. PTCA is delivering a balloon into target lesion position of blood vessel through femoral artery, then applying a pressure to expand the balloon so that the inside dimension of the narrowed vascular can be increased to improve the blood supplying to the cardiac muscle. However the restenosis rate after PTCA is as high as more than 50%. The application of metal stents made of stainless steel, cobalt alloy or nickel titanium alloy can decrease the restenosis rate to about 20% to 30%. Since 2003, drug eluting stent (DES) coated with a polymer layer containing drugs can decease the restenosis rate to about 10%, DES is regarded as a milestone of interventional therapy of coronary heart diseases. However, all these stents are not degradable and will stay in the blood vessel permanently. There is a big difference in mechanical characteristics between the blood vessel and the stent, which may cause chronic damage of blood vessel, atrophy of middle layer of the blood vessel, aneurysm formation and endometrial hyperplasia. Furthermore, young patients who are still in the growth period, the permanent stent cannot meet the need of the growth of the blood vessel. Simultaneously, the harmful elements released from stents to blood vessel are also the issue of metal stents. An ideal stent should perform the function of efficient mechanical support after intervention into the target lesion blood vessel in an appropriate period of 3 to 6 months, simultaneously release the drug to realize the function of therapy, and after that time, be gradually degraded to decrease the lesion effect of the stent on the blood vessel to prevent restenosis. Therefore, biodegradable polymer stent, such as polylactic acid stent, has attracted much attention. Polylactic acid can be degraded to non-toxic water and CO 2  which will be absorbed by the human body or breathed out, it has been approved by FDA as a biomaterial on the market. Completely biodegradable polymer stent which releases drugs during degrade process has also been reported. H. Tamai et al reported their results of intervention of 25 pieces of polylactic acid stents into hearts of 15 patients. Their results show that after 6 months the restenosis rate was at the same level of stainless steel stent. However, there are still problems with biodegradable polymer stents, such as: 
         [0004]    1) The strength and the deformation behavior of polymer stents are much different from metal stents. Because the biodegradable polymer stent is not strong, the thickness of polylactic acid stent is double that of stainless steel stent to provide suitable support, which will bring about obstructing to the blood stream. 
         [0005]    2) The polymer stents have to be heated to expand sufficiently, while heating may easily damage the blood vessel. 
         [0006]    3) The rebound rate of polymer stents is high, and visibility of the polymer is poor inside the vessel. 
         [0007]    4) The delivery system for biodegradable polymer stent is different from the delivery system which is widely used presently for metal stents. This would also affect the application of polymer stents. 
         [0008]    Biodegradable metal stents do not have those issues with polymer stents. Therefore, it is important to develop biodegradable metal stent and stent made of iron (Fe) is a new research subject. Iron is a common element existing in human body. The total amount of iron in an adult body is about 4 gram, and an adult will need to incept 10 to 15 mg of iron every day. Iron has better biocompatibility and mechanical properties. In 2001, Peuster firstly reported in vivo results of intervention of 16 iron stents (Fe content &gt;99.8%) into abdominal aorta of New Zealand rabbits for 6 to 18 months, most of the support bars of the stents degraded to some degree after 6 months and no obvious inflammation, restenosis and coagulation were found in 6 to 18 months experiments. [Peuster M, Wohlsein P, Brugmann M, et al, A novel approach to temporary stenting: degradable cardiovascular stents produced from corrodible metal-results 6˜18 months after implantation into New Zealand white rabbits. Heart, 2001; 86:563-569] 
         [0009]    Peuster further intervened stainless steel stents and iron stents into the abdominal aorta of mini-pigs in 2006. It was found that the degree of endometrial hyperplasia of both kinds of stents was about the same, and no excessive deposition and toxicity effect on the main organs of the pigs were found after histopathology analysis of these organs. And no toxic and side effects caused by corrosion product were found in the tissues close to the iron stent ribs. 
         [0010]    In 2006, Mueller et al used gene chip technology to reveal that one of the degradation products of pure iron stent, Fe 2+ , has an effect to inhibit the proliferation of smooth muscle cell. In 2008, Waksman et al intervened iron stents and Co—Cr alloy stents into pig&#39;s coronary blood vessel for 28 days and found that no obvious inflammation and embolism on surfaces of iron stents. And no obvious difference was found in intima thickness, intima area and occlusion rate between the two kinds of stents. 
         [0011]    In terms of strength, plasticity and processing ability, iron stent is close to stainless steel stent. Iron stent has better mechanical supporting ability than polymer stent. Comparing with Co—Cr alloy stent or stainless steel stent, iron stent has degradation ability and a better biocompatibility. The clinic applied balloon delivery system is also suitable for iron stent, it is easy for operation, and its cost is low. 
         [0012]    However there are still some shortcomings in iron stent: the low corrosion resistance of pure iron stent surface which can affect its mechanical support and be unhelpful to recovery of the lesion position of blood vessel, the low covering rate of endothelial cells on the stent surface in short time after the intervention into blood vessel, and the degradation rate of the iron stent which cannot be regulated to meet different needs. 
       SUMMARY OF THE INVENTION 
       [0013]    The present invention is about a degradable stent with a high corrosion resistivity and controllable degradation. In the 30 days after the stent intervened into blood vessel, the degradation rate of the stent maintains a low level and endue the surface with a good biocompatibility, which will be beneficial for endothelial cells to grow and cover the stent surface. And the stent can maintain a good mechanical supporting ability during 3 to 6 months and be degraded after 6 months part of the present invention is about pure iron stents and treated by surface modification using ion implantation technique, as follows: 
         [0014]    Implanting oxygen or nitrogen ions into the pure iron stent surface by ion implantation or plasma immersion ion implantation, the doses range is from 1×10 16  to 5×10 18  atoms/cm 2 , the energy range of the ions is from 5 to 100 KeV. 
         [0015]    Or implanting lanthanum (La), cerium (Ce) or strontium (Sr) ions into the pure iron stent surface by ion implantation or plasma immersion ion implantation, the doses range is from 1×10 16  to 5×10 18  atoms/cm 2 , the energy range of the ions is from 5 to 100 KeV. 
         [0016]    Or depositing a thin film of La, Ce, Sr, lanthana, ceria, strontia, iron or iron oxide on the pure iron stent using plasma immersion ion implantation. The thickness of the films is from 10 to 1000 nanometers, the grain size is from 10 to 200 nanometers. 
         [0017]    Comparing with existing technologies, the present invention of stents with O, N, La, Ce, Sr, lanthana, ceria, strontia, iron, iron oxide modified surface using ion implantation and/or plasma immersion ion implantation increases surface corrosion resistance of the stent. The elements for surface modification are non-toxic. The degradation rate of the iron stent can be effectively controlled and modulated. The stent maintains a low degradation rate in the 30 days after the intervention and endue the surface with a good biocompatibility which will be beneficial for endothelial cells to grow and cover the stent surface. The stent will provide sufficient mechanical supporting in 3 to 6 months period after intervention, and be degraded and gradually disappear after 6 months. Thus it will not have the issue of restenosis and late-thrombus formation etc. which may be caused by no-degradable permanent stent. The experiment results prove that the degradation rate of surface modified iron stent can go down more than 50% comparing with non-surface modified iron sten. Endothelial cells grow on the stent surface within 4 weeks, while on non-surface modified iron stent no endothelial cells existed but only degradation product. The degree of the degradation rate of iron stent can be modulated. In one aspect, this can be modulated by controlling the dosage of implanted ions, by the energy of the ion implantation, by the thickness or grain sizes of the deposited thin films, or other methods to meet the different needs of the stent. 
         [0018]    Above mentioned iron stent can be further magnetized in a magnetic field to become magnetic. The magnetized stent has the advantages to promote endothelial cells covering and prohibit smooth muscle cells growth, which is beneficial for prohibiting restenosis and coagulation. The mechanical supporting ability of the stent in 3 to 6 months period after intervention is sufficient, and the stent will be degraded and gradually disappear after 6 months. 
         [0019]    The other part of the present invention is fabricating of iron alloy stent. The iron alloy contains 0.01 to 0.5% of La, Ce or Sr. By adjusting the contents of La, Ce or Sr, the corrosion resistance/degradation rate of the stent can be modulated. The stent maintains a low degradation rate in the first 30 days after the intervention and endue the surface with a good biocompatibility which will be beneficial for endothelial cells to grow and cover the stent surface. The stent will provide sufficient mechanical supporting in 3 to 6 months period after intervention, and be degraded and gradually disappear after 6 months. Thus it will not have the issue of restenosis and late-thrombus formation etc. which may be caused by no-degradable permanent stent. The experiment results prove that the degradation rate of the iron alloy stent can go down more than 50% in the first 30 days after being intervened into blood vessel, comparing with pure iron stent. The degradation rate of iron alloy stent can be modulated by controlling quantity of alloying elements to meet different needs of the stent. 
         [0020]    Above mentioned iron alloy stent is further treated by surface modification using ion implantation technique to further improve the surface corrosion resistance of stent and modulate the degradation rate. The surface modification treatment is as follows: 
         [0021]    Implanting oxygen or nitrogen ions into the iron alloy stent surface by ion implantation or plasma immersion ion implantation, the doses range is from 1×10 16  to 5×10 18  atoms/cm 2 , the energy range of the ions is from 5 to 100 KeV. 
         [0022]    Or implanting lanthanum (La), cerium (Ce) or strontium (Sr) ions into the iron alloy stent surface by ion implantation or plasma immersion ion implantation, the doses range is from 1×10 16  to 5×10 18  atoms/cm 2 , the energy range of the ions is from 5 to 100 KeV. 
         [0023]    Or depositing a thin film of La, Ce, Sr, lanthana, ceria, strontia, iron or iron oxide on the iron alloy stent using plasma immersion ion implantation. The thickness of the films is from 10 to 1000 nanometers, the grain size is from 10 to 200 nanometers. 
         [0024]    Above mentioned iron alloy stent can be further magnetized in a magnetic field. The magnetized stent has advantages to promote endothelial cells covering and prohibit smooth muscle cells growth, which can be beneficial to prohibit restenosis and coagulation. 
         [0025]    The present disclosure is further demonstrated by the figures and the examples, in comparison of controlling samples of pure iron stent. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0026]      FIG. 1  is a SEM micrograph of surface morphology of the stent described in example 5 intervened into dog&#39;s femoral artery for 4 weeks. 
           [0027]      FIG. 2  is a SEM micrograph of surface morphology of untreated pure iron stent intervened into dog&#39;s femoral artery for 4 weeks. 
           [0028]      FIG. 3  is surface morphology of the stent in example 95 with iron oxide film cultured with endothelial cells for 3 days. 
           [0029]      FIG. 4  is surface morphology of the stainless steel stent cultured with endothelial cells for 3 days. 
       
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
       [0030]    The following EXAMPLES illustrate various aspects of the making the stent herein. They are not intended to limit the scope of the invention. 
       Example 1 to 9 
       [0031]    A biodegradable pure iron stent is treated by the following plasma process: 
         [0032]    Oxygen ions are implanted into the pure stent surface by ion implantation or plasma immersion ion implantation, the doses range is from 1×1016 to 5×1018 atoms/cm2, the energy range of the ions is from 5 to 100 KeV. The treatment parameters and test results of the example 1-9 are given in Table 1. 
         [0033]    For verifying the corrosion resistance and in vitro degradation properties of the stents, polarization testing and immersion corrosion testing are performed using simulated body fluid solution (SBF, containing NaCl:8.04, KCl:0.23, NaHCO3:0.35, K2HPO4.3H2O:0.24, MgCl2.6H2O:0.31, CaCl2:0.29, Na2SO4:0.07, TRIS:6.12). The results are given in Table 1. It is proved that the corrosion currents and the weight loss are all significantly decreased. Less weight loss also means a more stable mechanical supporting of the stent. 
         [0000]    
       
         
               
               
               
               
               
               
             
               
               
               
               
               
               
             
           
               
                   
                 TABLE 1 
               
               
                   
                   
               
               
                   
                   
                   
                   
                   
                 Weight loss after 
               
               
                   
                   
                 Implanted doses 
                   
                 Corrosion current 
                 immersion 216 
               
               
                   
                 method 
                 (atoms/cm 2 ) 
                 Ion energy (KeV) 
                 (mA/cm 2 ) 
                 hours (mg) 
               
               
                   
                   
               
             
             
               
                   
               
             
          
           
               
                 Controlling sample 
                 Unmodified iron 
                   
                   
                 0.59 
                 0.460 
               
               
                   
                 stent 
               
               
                 Example 1 
                 Ion implantation 
                 1 × 10 16   
                 5 
                 0.40 
                 0.340 
               
               
                 Example 2 
                 Plasma immersion 
                 1 × 10 16   
                 40 
                 0.45 
                 0.390 
               
               
                   
                 ion implantation 
               
               
                 Example 3 
                 Ion implantation 
                 1 × 10 16   
                 100 
                 0.49 
                 0.416 
               
               
                 Example 4 
                 Plasma immersion 
                 1 × 10 17   
                 5 
                 0.27 
                 0.258 
               
               
                   
                 ion implantation 
               
               
                 Example 5 
                 Plasma immersion 
                 1 × 10 17   
                 40 
                 0.08 
                 0.092 
               
               
                   
                 ion implantation 
               
               
                 Example 6 
                 Ion implantation 
                 1 × 10 17   
                 100 
                 0.12 
                 0.112 
               
               
                 Example 7 
                 Plasma immersion 
                 5 × 10 18   
                 5 
                 0.36 
                 0.306 
               
               
                   
                 ion implantation 
               
               
                 Example 8 
                 Ion implantation 
                 5 × 10 18   
                 40 
                 0.13 
                 0.121 
               
               
                 Example 9 
                 Plasma immersion 
                 5 × 10 18   
                 100 
                 0.11 
                 0.105 
               
               
                   
                 ion implantation 
               
               
                   
               
             
          
         
       
     
         [0034]      FIG. 1  is a SEM micrograph of surface morphology of the stent described in example 5 intervened into a dog&#39;s femoral artery for 4 weeks.  FIG. 2  is a SEM micrograph of surface morphology of the controlling sample of untreated pure iron stent intervened into the dog&#39;s femoral artery for 4 weeks. Comparing  FIG. 1  with  FIG. 2 , it shows that after oxygen ions implantation, endothelial cells have covered on the modified iron stent completely, but almost no endothelial cells grew on the untreated iron stent. This result indicates that biocompatibility of the oxygen ions implanted iron stent is significantly improved. 
       Example 10 to 18 
       [0035]    A biodegradable pure iron stent is treated by the following processes: 
         [0036]    Nitrogen ions are implanted into the pure iron stent surface by ion implantation or plasma immersion ion implantation, the doses range is from 1× 1016  to 5×10 18  atoms/cm 2 , the energy range of the ions is from 5 to 100 KeV. The parameters for example 10-18 are given in Table 2. 
         [0037]    Table 2 also shows the corrosion and in vitro degradation properties of the stents in these examples by polarization testing and immersion corrosion testing. It is proved that the corrosion resistance of the surface modified stent is significantly improved as showed by the significant lower weight loss after immersed in SBF for 9 days. And the lowest weight loss is ⅓ of that of the untreated one. 
         [0000]    
       
         
               
               
               
               
               
               
             
               
               
               
               
               
               
             
           
               
                   
                 TABLE 2 
               
               
                   
                   
               
               
                   
                 Surface 
                   
                   
                   
                 Weight loss after 
               
               
                   
                 modification 
                 Implanted doses 
                   
                 Corrosion current 
                 immersion 216 
               
               
                   
                 method 
                 (atoms/cm 2 ) 
                 Ion energy (KeV) 
                 (mA/cm 2 ) 
                 hours (mg) 
               
               
                   
                   
               
             
             
               
                   
               
             
          
           
               
                 Controlling sample 
                 Unmodified iron 
                   
                   
                 0.59 
                 0.460 
               
               
                   
                 stent 
               
               
                 example 10 
                 Ion implantation 
                 1 × 10 16   
                 5 
                 0.45 
                 0.415 
               
               
                 example t 11 
                 Plasma immersion 
                 1 × 10 16   
                 40 
                 0.51 
                 0.438 
               
               
                   
                 ion implantation 
               
               
                 example 12 
                 Ion implantation 
                 1 × 10 16   
                 100 
                 0.53 
                 0.445 
               
               
                 example 13 
                 Plasma immersion 
                 1 × 10 17   
                 5 
                 0.35 
                 0.318 
               
               
                   
                 ion implantation 
               
               
                 example 14 
                 Plasma immersion 
                 1 × 10 17   
                 40 
                 0.18 
                 0.163 
               
               
                   
                 ion implantation 
               
               
                 example 15 
                 Ion implantation 
                 1 × 10 17   
                 100 
                 0.22 
                 0.239 
               
               
                 example 16 
                 Plasma immersion 
                 5 × 10 18   
                 5 
                 0.41 
                 0.352 
               
               
                   
                 ion implantation 
               
               
                 example 17 
                 Plasma immersion 
                 5 × 10 18   
                 40 
                 0.20 
                 0.169 
               
               
                   
                 ion implantation 
               
               
                 example 18 
                 Ion implantation 
                 5 × 10 18   
                 100 
                 0.18 
                 0.158 
               
               
                   
               
             
          
         
       
     
       Example 19 to 27 
       [0038]    A biodegradable pure iron stent is treated by the following processes: 
         [0039]    La ions are implanted into the pure iron stent surface by ion implantation or plasma immersion ion implantation, the doses range is from 1×10 16  to 5×10 18  atoms/cm 2 , the energy range of the ions is from 5 to 100 KeV. The parameters for example 19-27 are given in Table 3. 
         [0040]    Table 3 also gives the results of polarization testing, immersion corrosion testing and activated partial thromboplastin time (APTT). It is proved that corrosion current and weight loss are significantly decreased and APTT is increased. These results show that La ion implantation modifies the blood compatibility, corrosion resistance and supporting ability of the iron stent. 
         [0000]    
       
         
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
             
           
               
                   
                 TABLE 3 
               
               
                   
                   
               
               
                   
                 Surface 
                 Implanted 
                 Ion 
                 Corrosion 
                 Weight loss 
                   
               
               
                   
                 modification 
                 doses 
                 energy 
                 current 
                 after immersion 
               
               
                   
                 method 
                 (atoms/cm 2 ) 
                 (KeV) 
                 (mA/cm 2 ) 
                 216 hours (mg) 
                 APTT (s) 
               
               
                   
                   
               
             
             
               
                   
               
             
          
           
               
                 Controlling 
                 Untreated pure 
                   
                   
                 0.57 
                 0.481 
                 39.5 
               
               
                 sample 
                 iron 
               
               
                 Example 19 
                 Ion implantation 
                 1 × 10 16   
                 5 
                 0.38 
                 0.316 
                 41.5 
               
               
                 Example 20 
                 Plasma immersion 
                 1 × 10 16   
                 40 
                 0.41 
                 0.342 
                 41.0 
               
               
                   
                 ion implantation 
               
               
                 Example 21 
                 Ion implantation 
                 1 × 10 16   
                 100 
                 0.44 
                 0.373 
                 42.5 
               
               
                 Example 22 
                 Plasma immersion 
                 1 × 10 17   
                 5 
                 0.24 
                 0.234 
                 41.5 
               
               
                   
                 ion implantation 
               
               
                 Example 23 
                 Ion implantation 
                 1 × 10 17   
                 40 
                 0.20 
                 0.191 
                 42.0 
               
               
                 Example 24 
                 Ion implantation 
                 1 × 10 17   
                 100 
                 0.25 
                 0.238 
                 42.0 
               
               
                 Example 25 
                 Plasma immersion 
                 5 × 10 18   
                 5 
                 0.34 
                 0.288 
                 42.5 
               
               
                   
                 ion implantation 
               
               
                 Example 26 
                 Plasma immersion 
                 5 × 10 18   
                 40 
                 0.24 
                 0.226 
                 41.0 
               
               
                   
                 ion implantation 
               
               
                 Example 27 
                 Ion implantation 
                 5 × 10 18   
                 100 
                 0.22 
                 0.202 
                 42.5 
               
               
                   
               
             
          
         
       
     
       Example 28 to 36 
       [0041]    A biodegradable pure iron stent is treated by the following processes: 
         [0042]    Ce ions are implanted into the pure iron stent surface by ion implantation or plasma immersion ion implantation, the doses range is from 1×10 16  to 5×10 18  atoms/cm 2 , the energy range of the ions is from 5 to 100 KeV. The parameters for example 28-36 are given in Table 4. 
         [0043]    Table 4 also gives the results of polarization testing, immersion corrosion testing and activated partial thromboplastin time (APTT). The corrosion current and the weight loss are significantly decreased and APTT is increased. These results show that Ce ion implantation modified the blood compatibility, corrosion resistance and supporting ability of the iron stent. 
         [0000]    
       
         
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
             
           
               
                   
                 TABLE 4 
               
               
                   
                   
               
               
                   
                 Surface 
                 Implanted 
                 Ion 
                 Corrosion 
                 Weight loss 
                   
               
               
                   
                 modification 
                 doses 
                 energy 
                 current 
                 after immersion 
               
               
                   
                 method 
                 (atoms/cm 2 ) 
                 (KeV) 
                 (mA/cm 2 ) 
                 216 hours (mg) 
                 APTT (s) 
               
               
                   
                   
               
             
             
               
                   
               
             
          
           
               
                 Controlling 
                 Unmodified pure 
                   
                   
                 0.58 
                 0.481 
                 39.7 
               
               
                 sample 
                 iron 
               
               
                 Example 28 
                 Ion implantation 
                 1 × 10 16   
                 5 
                 0.41 
                 0.337 
                 41.2 
               
               
                 Example 29 
                 Plasma immersion 
                 1 × 10 16   
                 40 
                 0.38 
                 0.309 
                 42.6 
               
               
                   
                 ion implantation 
               
               
                 Example 30 
                 Ion implantation 
                 1 × 10 16   
                 100 
                 0.47 
                 0.399 
                 41.0 
               
               
                 Example 31 
                 Plasma immersion 
                 1 × 10 17   
                 5 
                 0.27 
                 0.248 
                 42.0 
               
               
                   
                 ion implantation 
               
               
                 Example 32 
                 Plasma immersion 
                 1 × 10 17   
                 40 
                 0.19 
                 0.177 
                 43.5 
               
               
                   
                 ion implantation 
               
               
                 Example 33 
                 Ion implantation 
                 1 × 10 17   
                 100 
                 0.23 
                 0.217 
                 41.8 
               
               
                 Example 34 
                 Plasma immersion 
                 5 × 10 18   
                 5 
                 0.37 
                 0.301 
                 42.5 
               
               
                   
                 ion implantation 
               
               
                 Example 35 
                 Plasma immersion 
                 5 × 10 18   
                 40 
                 0.28 
                 0.238 
                 41.5 
               
               
                   
                 ion implantation 
               
               
                 Example 36 
                 Ion implantation 
                 5 × 10 18   
                 100 
                 0.26 
                 0.221 
                 43.0 
               
               
                   
               
             
          
         
       
     
       Example 37 to 45 
       [0044]    A biodegradable pure iron stent is treated by the following processes: 
         [0045]    Sr ions are implanted into the pure iron stent surface by ion implantation or plasma immersion ion implantation, the doses range is from 1×10 16  to 5×10 18  atoms/cm 2 , the energy range of the ions is from 5 to 100 KeV. The parameters for example 37-45 are given in Table 5. 
         [0046]    Table 5 also gives the results of polarization testing, immersion corrosion testing and activated partial thromboplastin time (APTT). It is proved that the corrosion current and the weight loss are significantly decreased and APTT is increased. These results show that Sr ion implantation modified the blood compatibility, corrosion resistance and supporting ability of the iron stent. 
         [0000]    
       
         
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
             
           
               
                   
                 TABLE 5 
               
               
                   
                   
               
               
                   
                 Surface 
                 Implanted 
                 Ion 
                 Corrosion 
                 Weight loss 
                   
               
               
                   
                 modification 
                 doses 
                 energy 
                 current 
                 after immersion 
               
               
                   
                 method 
                 (atoms/cm 2 ) 
                 (KeV) 
                 (mA/cm 2 ) 
                 216 hours (mg) 
                 APTT (s) 
               
               
                   
                   
               
             
             
               
                   
               
             
          
           
               
                 Controlling 
                 Unmodified pure 
                   
                   
                 0.56 
                 0.466 
                 40.0 
               
               
                 sample 
                 iron 
               
               
                 Example 37 
                 Ion implantation 
                 1 × 10 16   
                 5 
                 0.37 
                 0.305 
                 42.5 
               
               
                 Example 38 
                 Plasma immersion 
                 1 × 10 16   
                 40 
                 0.32 
                 0.278 
                 43.0 
               
               
                   
                 ion implantation 
               
               
                 Example 39 
                 Ion implantation 
                 1 × 10 16   
                 100 
                 0.41 
                 0.357 
                 41.5 
               
               
                 Example 40 
                 Plasma immersion 
                 1 × 10 17   
                 5 
                 0.28 
                 0.248 
                 43.5 
               
               
                   
                 ion implantation 
               
               
                 Example 41 
                 Plasma immersion 
                 1 × 10 17   
                 40 
                 0.23 
                 0.227 
                 43.8 
               
               
                   
                 ion implantation 
               
               
                 Example 42 
                 Ion implantation 
                 1 × 10 17   
                 100 
                 0.31 
                 0.269 
                 42.5 
               
               
                 Example 43 
                 Plasma immersion 
                 5 × 10 18   
                 5 
                 0.35 
                 0.294 
                 42.6 
               
               
                   
                 ion implantation 
               
               
                 Example 44 
                 Plasma immersion 
                 5 × 10 18   
                 40 
                 0.22 
                 0.214 
                 42.2 
               
               
                   
                 ion implantation 
               
               
                 Example 45 
                 Ion implantation 
                 5 × 10 18   
                 100 
                 0.21 
                 0.193 
                 41.5 
               
               
                   
               
             
          
         
       
     
       Example 46 to 57 
       [0047]    A biodegradable pure iron stent is treated by the following processes: 
         [0048]    La thin films are deposited onto the pure iron stent surface by plasma deposition process. The film thickness range is from 10 to 1000 nanometer. The parameters for example 46-57 are given in Table 6. 
         [0049]    Table 6 also shows the result of average corrosion rate and APTT, the “average corrosion rate (mm/year) is deduced from the average data from testing for 216 hours. It is proved that the corrosion resistance and anticoagulation properties are significantly increased. 
         [0000]    
       
         
               
               
               
               
               
             
               
               
               
               
               
             
           
               
                   
                 TABLE 6 
               
               
                   
                   
               
               
                   
                 Film 
                   
                   
                   
               
               
                   
                 thickness 
                 Grain 
                 Average corrosion 
               
               
                   
                 (nm) 
                 size (nm) 
                 rate (mm/year) 
                 APTT(s) 
               
               
                   
                   
               
             
             
               
                   
               
             
          
           
               
                 Controlling 
                 Unmodified 
                   
                 0.039 
                 39.5 
               
               
                 sample 
                 iron stent 
               
               
                 Example 46 
                 10 
                 10 
                 0.028 
                 41.5 
               
               
                 Example 47 
                 200 
                 10 
                 0.012 
                 43.0 
               
               
                 Example 48 
                 500 
                 10 
                 0.016 
                 42.5 
               
               
                 Example 49 
                 1000 
                 10 
                 0.019 
                 43.1 
               
               
                 Example 50 
                 10 
                 100 
                 0.030 
                 41.1 
               
               
                 Example 51 
                 200 
                 100 
                 0.019 
                 42.5 
               
               
                 Example 52 
                 500 
                 100 
                 0.024 
                 42.2 
               
               
                 Example 53 
                 1000 
                 100 
                 0.028 
                 42.5 
               
               
                 Example 54 
                 10 
                 200 
                 0.033 
                 41.0 
               
               
                 Example 55 
                 200 
                 200 
                 0.016 
                 41.6 
               
               
                 Example 56 
                 500 
                 200 
                 0.021 
                 42.7 
               
               
                 Example 57 
                 1000 
                 200 
                 0.022 
                 42.1 
               
               
                   
               
             
          
         
       
     
       Example 58 to 69 
       [0050]    A biodegradable pure iron stent is treated by the following processes: 
         [0051]    Ce thin films are deposited onto the pure iron stent surface by plasma deposition process. The film thickness range is from 10 to 1000 nanometer. The parameters for example 58-69 are given in Table 7. 
         [0052]    Table 7 also gives the results of average corrosion rate and APTT of the surface modified stent. It is proved that the stent with Ce thin film has significantly increased corrosion resistance and anticoagulation properties. 
         [0000]    
       
         
               
               
               
               
               
             
               
               
               
               
               
             
           
               
                   
                 TABLE 7 
               
               
                   
                   
               
               
                   
                 Film 
                   
                   
                   
               
               
                   
                 thickness 
                 Grain 
                 Average corrosion 
               
               
                   
                 (nm) 
                 size (nm) 
                 rate (mm/year) 
                 APTT(s) 
               
               
                   
                   
               
             
             
               
                   
               
             
          
           
               
                 Controlling 
                 Unmodified 
                   
                 0.039 
                 39.5 
               
               
                 sample 
                 iron stent 
               
               
                 Example 58 
                 10 
                 10 
                 0.033 
                 41.0 
               
               
                 Example 59 
                 200 
                 10 
                 0.019 
                 42.5 
               
               
                 Example 60 
                 500 
                 10 
                 0.017 
                 42.0 
               
               
                 Example 61 
                 1000 
                 10 
                 0.020 
                 42.5 
               
               
                 Example 62 
                 10 
                 100 
                 0.035 
                 41.6 
               
               
                 Example 63 
                 200 
                 100 
                 0.018 
                 42.0 
               
               
                 Example 64 
                 500 
                 100 
                 0.020 
                 42.8 
               
               
                 Example 65 
                 1000 
                 100 
                 0.019 
                 41.5 
               
               
                 Example 66 
                 10 
                 200 
                 0.036 
                 41.6 
               
               
                 Example 67 
                 200 
                 200 
                 0.023 
                 41.9 
               
               
                 Example 68 
                 500 
                 200 
                 0.018 
                 43.6 
               
               
                 Example 69 
                 1000 
                 200 
                 0.017 
                 41.7 
               
               
                   
               
             
          
         
       
     
       Example 70 to 81 
       [0053]    A biodegradable pure iron stent is treated by the following processes: 
         [0054]    Sr thin films are deposited onto the pure iron stent surface by plasma deposition process. The film thickness range is from 10 to 1000 nanometer. The parameters for example 70-81 are given in Table 8. 
         [0055]    Table 8 also gives the results of average corrosion rate and APTT of the stent with Sr thin film. It is proved that the stent with Sr thin film has significantly increased corrosion resistance and anticoagulation properties. 
         [0000]    
       
         
               
               
               
               
               
             
               
               
               
               
               
             
           
               
                   
                 TABLE 8 
               
               
                   
                   
               
               
                   
                 Film 
                   
                   
                   
               
               
                   
                 thickness 
                 Grain 
                 Average corrosion 
               
               
                   
                 (nm) 
                 size (nm) 
                 rate (mm/year) 
                 APTT(s) 
               
               
                   
                   
               
             
             
               
                   
               
             
          
           
               
                 Controlling 
                 Unmodified 
                   
                 0.039 
                 39.5 
               
               
                 sample 
                 iron stent 
               
               
                 Example 70 
                 10 
                 10 
                 0.031 
                 41.5 
               
               
                 Example 71 
                 200 
                 10 
                 0.023 
                 43.2 
               
               
                 Example 72 
                 500 
                 10 
                 0.017 
                 42.6 
               
               
                 Example 73 
                 1000 
                 10 
                 0.019 
                 41.6 
               
               
                 Example 74 
                 10 
                 100 
                 0.033 
                 42.4 
               
               
                 Example 75 
                 200 
                 100 
                 0.015 
                 43.0 
               
               
                 Example 76 
                 500 
                 100 
                 0.017 
                 42.6 
               
               
                 Example 77 
                 1000 
                 100 
                 0.021 
                 41.9 
               
               
                 Example 78 
                 10 
                 200 
                 0.035 
                 42.1 
               
               
                 Example 79 
                 200 
                 200 
                 0.021 
                 42.5 
               
               
                 Example 80 
                 500 
                 200 
                 0.018 
                 42.6 
               
               
                 Example 81 
                 1000 
                 200 
                 0.022 
                 42.8 
               
               
                   
               
             
          
         
       
     
       Example 82 to 93 
       [0056]    A biodegradable pure iron stent is treated by the following processes: 
         [0057]    Fe thin films are deposited onto the pure iron stent surface by plasma deposition process. The film thickness range is from 10 to 1000 nanometer. The parameters for example 82-93 are given in Table 9. 
         [0058]    Table 9 also gives the results of average corrosion rate and APTT of the stent with Fe thin film. It is proved that the stent with Fe thin film has significantly increased corrosion resistance. 
         [0000]    
       
         
               
               
               
               
             
               
               
               
               
             
           
               
                   
                 TABLE 9 
               
               
                   
                   
               
               
                   
                 Film thickness 
                   
                 Average corrosion rate 
               
               
                   
                 (nm) 
                 Grain size (nm) 
                 (mm/year) 
               
               
                   
                   
               
             
             
               
                   
               
             
          
           
               
                 Controlling 
                 Unmodified 
                   
                 0.039 
               
               
                 sample 
                 iron stent 
               
               
                 Example 82 
                 10 
                 10 
                 0.029 
               
               
                 Example 83 
                 100 
                 10 
                 0.014 
               
               
                 Example 84 
                 1000 
                 10 
                 0.011 
               
               
                 Example 85 
                 2000 
                 10 
                 0.013 
               
               
                 Example 86 
                 10 
                 100 
                 0.032 
               
               
                 Example 87 
                 100 
                 100 
                 0.021 
               
               
                 Example 88 
                 1000 
                 100 
                 0.023 
               
               
                 Example 89 
                 2000 
                 100 
                 0.024 
               
               
                 Example 90 
                 10 
                 200 
                 0.036 
               
               
                 Example 91 
                 100 
                 200 
                 0.033 
               
               
                 Example 92 
                 1000 
                 200 
                 0.032 
               
               
                 Example 93 
                 2000 
                 200 
                 0.035 
               
               
                   
               
             
          
         
       
     
       Example 94 to 105 
       [0059]    A biodegradable pure iron stent is treated by the following processes: 
         [0060]    Iron oxide thin films are deposited onto the pure iron stent surface by plasma deposition process. The film thickness range is from 10 to 1000 nanometer. The parameters for example 94-105 are given in Table 10. 
         [0061]    Table 10 also gives the results of average corrosion rate and APTT. It is proved that the stent with iron oxide thin film has significantly increased corrosion resistance and anticoagulation properties. 
         [0000]    
       
         
               
               
               
               
               
             
               
               
               
               
               
             
           
               
                   
                 TABLE 10 
               
               
                   
                   
               
               
                   
                 Film 
                 Grain  
                 Corrosion current 
                   
               
               
                   
                 thickness (nm) 
                 size (nm) 
                 (mA/cm 2 ) 
                 APTT (s) 
               
               
                   
                   
               
             
             
               
                   
               
             
          
           
               
                 Controlling 
                 Unmodified 
                   
                 0.58 
                 39.5 
               
               
                 sample 
                 iron stent 
               
               
                 Example 94 
                 10 
                 10 
                 0.45 
                 40.5 
               
               
                 Example 95 
                 100 
                 10 
                 0.12 
                 43.0 
               
               
                 Example 96 
                 1000 
                 10 
                 0.17 
                 42.5 
               
               
                 Example 97 
                 2000 
                 10 
                 0.22 
                 43.1 
               
               
                 Example 98 
                 10 
                 100 
                 0.47 
                 42.0 
               
               
                 Example 99 
                 100 
                 100 
                 0.19 
                 41.0 
               
               
                 Example 100 
                 1000 
                 100 
                 0.25 
                 42.6 
               
               
                 Example 101 
                 2000 
                 100 
                 0.29 
                 41.5 
               
               
                 Example 102 
                 10 
                 200 
                 0.49 
                 42.0 
               
               
                 Example 103 
                 100 
                 200 
                 0.21 
                 41.0 
               
               
                 Example 104 
                 1000 
                 200 
                 0.26 
                 41.5 
               
               
                 Example 105 
                 2000 
                 200 
                 0.27 
                 40.0 
               
               
                   
               
             
          
         
       
     
         [0062]      FIG. 3  is surface morphology of the endothelial cells on the stent with iron oxide film described in Example 95 cultured with endothelial cells for 3 days. 
         [0063]      FIG. 4  is surface morphology of the endothelial cells on the stainless steel stent cultured with endothelial cells for 3 days. 
         [0064]    Comparing  FIG. 3  with  FIG. 4 , it shows that endothelial cells grow more on the iron stent with iron oxide film. This means that the biocompatibility of iron oxide film coated stent is better. 
         [0065]    The iron stent after surface modification is treated further in magnetic field. The magnetic density is not lower than 100 mT. After magnetization the stent is implanted in the blood vessel and it is found that the stent is fully covered with ECs in 2-5 days. In comparison to magnetized stent, ECs covering on non-magnetized stent occurs in more than 10 days. It shows that magnetization of stent can help endothelialization on the iron stent. 
       Example 106 to 114 
       [0066]    A biodegradable iron alloy stent contains La, Ce or Sr from 0.01 to 0.5 atom %. 
         [0067]    example 106-114 about the iron alloy stents with different amount of alloying elements are given in Table 11. Polarization testing and immersion corrosion testing are performed in simulated body fluid solution (SBF, containing NaCl:8.04, KCl:0.23, NaHCO3:0.35, K2HPO4.3H2O:0.24, MgCl2.6H2O:0.31, CaCl2:0.29, Na2SO4:0.07, TRIS:6.12) to verify the corrosion and in vitro degradation properties of the stents and the results are also given in Table 11. The test results show that the corrosion currents and the weight loss rate in SBF for 187 hours all are decreased. (The corrosion rate in Table 11 is deduced from data of 187 hours immersion.) 
         [0000]    
       
         
               
               
               
               
               
             
               
               
               
               
               
             
           
               
                   
                 TABLE 11 
               
               
                   
                   
               
               
                   
                   
                   
                 Corrosion 
                   
               
               
                   
                 Alloy 
                   
                 current 
                 Average corrosion 
               
               
                   
                 element 
                 Atom % 
                 (mA/cm 2 ) 
                 rate (mm/year) 
               
               
                   
                   
               
             
             
               
                   
               
             
          
           
               
                 Controlling 
                   
                 Pure iron 
                 0.57 
                 0.038 
               
               
                 sample 
               
               
                 Example 106 
                 La 
                 0.01% 
                 0.46 
                 0.032 
               
               
                 Example 107 
                 La 
                 0.25% 
                 0.31 
                 0.023 
               
               
                 Example 108 
                 La 
                  0.5% 
                 0.37 
                 0.029 
               
               
                 Example 109 
                 Ce 
                 0.01% 
                 0.44 
                 0.032 
               
               
                 Example 110 
                 Ce 
                 0.25% 
                 0.27 
                 0.020 
               
               
                 Example 111 
                 Ce 
                  0.5% 
                 0.39 
                 0.030 
               
               
                 Example 112 
                 Sr 
                 0.01% 
                 0.38 
                 0.028 
               
               
                 Example 113 
                 Sr 
                 0.25% 
                 0.36 
                 0.025 
               
               
                 Example 114 
                 Sr 
                  0.5% 
                 0.47 
                 0.033 
               
               
                   
               
             
          
         
       
     
       Example 115 to 117 
       [0068]    A biodegradable iron stent contains La, Ce or Sr from 0.01 atom % to 0.5 atom %. Furthermore, oxygen or nitrogen ions are implanted into the stent surface by ion implantation or plasma immersion ion implantation. The doses are from 1×10 16  to 5×10 18  atoms/cm 2 , the energy of the ions are from 5 to 100 KeV. 
         [0069]    The treatment conditions and test results of example 115-117 are given in Table 12. 
         [0000]    
       
         
               
               
               
               
               
             
               
               
               
               
               
             
           
               
                   
                 TABLE 12 
               
               
                   
                   
               
               
                   
                 Controlling 
                 Example 
                 Example 
                   
               
               
                   
                 sample 
                 115 
                 116 
                 Example 117 
               
               
                   
                   
               
             
             
               
                   
               
             
          
           
               
                 Alloy content 
                 Not added 
                 La 0.01% 
                 Ce0.25% 
                 Sr0.5% 
               
               
                 Method for 
                 No-treated 
                 Ion 
                 PIII 
                 Ion 
               
               
                 surface treatment 
                   
                 implantation 
                   
                 implantation 
               
               
                 Element 
                   
                 O+ 
                 N+ 
                 O+ 
               
               
                 implanted 
               
               
                 doses (atom/cm 2 ) 
                   
                 1 × 10 16   
                 5 × 10 17   
                 5 × 10 18   
               
               
                 energy (KeV) 
                   
                 5 
                 50 
                 100 
               
               
                 Corrosion current 
                 0.57 
                 0.37 
                 0.12 
                 0.10 
               
               
                 (mA/cm 2 ) 
               
               
                   
               
             
          
         
       
     
       Example 118 to 120 
       [0070]    A biodegradable iron stent contains La, Ce or Sr from 0.01 to 0.5 atom %. Furthermore, La, Ce or Sr ions are implanted into the stent surface by ion implantation or plasma immersion ion implantation. The doses are from 1×10 16  to 5×10 18  atoms/cm 2 , the energy of the ions are from 5 to 100 KeV. 
         [0071]    The treatment conditions and test results of example 118-120 are given in Table 13. 
         [0000]    
       
         
               
               
               
               
               
             
               
               
               
               
               
             
           
               
                   
                 TABLE 13 
               
               
                   
                   
               
               
                   
                 Controlling 
                   
                   
                   
               
               
                   
                 sample 
                 Example 118 
                 Example 119 
                 Example 120 
               
               
                   
                   
               
             
             
               
                   
               
             
          
           
               
                 Alloy content 
                 Pure iron 
                 La 0.01% 
                 Ce 0.25% 
                 Sr 0.5% 
               
               
                 Method for 
                 untreated 
                 Ion 
                 Plasma 
                 Ion 
               
               
                 surface 
                   
                 implantation 
                 immersion 
                 implantation 
               
               
                 treatment 
                   
                   
                 ion 
               
               
                   
                   
                   
                 implantation 
               
               
                 Element 
                   
                 La 
                 Ce 
                 Sr 
               
               
                 implanted 
               
               
                 doses 
                   
                 1 × 10 16   
                 5 × 10 17   
                 5 × 10 18   
               
               
                 (atom/cm 2 ) 
               
               
                 energy (KeV) 
                   
                 5 
                 50 
                 100 
               
               
                 Corrosion 
                 0.57 
                 0.39 
                 0.23 
                 0.20 
               
               
                 current 
               
               
                 (mA/cm 2 ) 
               
               
                   
               
             
          
         
       
     
       Example 121 to 129 
       [0072]    A biodegradable iron stent containing La, Ce or Sr from 0.01 atom % to 0.5 atom %: the stent are further treated by plasma deposition of La, Ce, Sr, lanthana, ceria, strontia, iron or iron oxide thin film. The thickness of the films is from 10 to 1000 nanometers, the grain size is from 10 to 200 nanometers. The treatment conditions and test results of example 121-129 are given in Table 14. 
         [0000]    
       
         
               
               
               
               
               
               
             
               
               
               
               
               
               
             
           
               
                   
                 TABLE 14 
               
               
                   
                   
               
               
                   
                   
                   
                   
                   
                 Average 
               
               
                   
                   
                   
                   
                 Thickness 
                 corrosion 
               
               
                   
                 Alloy 
                 Deposition 
                 Grain size 
                 of the 
                 rate 
               
               
                   
                 content 
                 material 
                 (nm) 
                 films (nm) 
                 (mm/year) 
               
               
                   
                   
               
             
             
               
                   
               
             
          
           
               
                 Controlling 
                 Untreat 
                   
                   
                   
                 0.039 
               
               
                 sample 
                 pure iron 
               
               
                 Example 121 
                 La 0.01% 
                 La 
                 10 
                 10 
                 0.027 
               
               
                 Example 122 
                 Ce 0.25% 
                 Ce 
                 100 
                 700 
                 0.016 
               
               
                 Example 123 
                 La 0.01% 
                 La 
                 200 
                 10 
                 0.031 
               
               
                 Example 124 
                 Ce 0.25% 
                 strontia 
                 10 
                 500 
                 0.015 
               
               
                 Example 125 
                 Sr 0.5% 
                 Ceria 
                 100 
                 1000 
                 0.017 
               
               
                 Example 126 
                 Sr 0.5% 
                 Lanthana 
                 200 
                 1000 
                 0.020 
               
               
                 Example 127 
                 La 0.01% 
                 Fe 
                 10 
                 10 
                 0.030 
               
               
                 Example 128 
                 Ce 0.3% 
                 Iron oxide 
                 100 
                 1000 
                 0.028 
               
               
                 Example 129 
                 Sr 0.4% 
                 Fe 
                 200 
                 1000 
                 0.029 
               
               
                   
               
             
          
         
       
     
         [0073]    The surface treated degradable iron stent is further magnetized in magnetic field. The magnetic density is not lower than 100 mT. After magnetization the stent is implanted in the blood vessel and it is found that the stent is fully covered with ECs in 2-5 days. In comparison to magnetized stent, ECs covering on non-magnetized stent occurs in more than 10 days. This proves that magnetization of stent helps endothelialization of iron stent.