CN111803252A - A kind of stainless steel and its preparation method and drug-eluting stent - Google Patents

Abstract

The invention relates to the technical field of stainless steel, in particular to a stainless steel and a preparation method thereof and a drug-eluting stent. The large holes and small holes on the surface of the stainless steel provided by the invention are generated in situ and are closely combined with the stainless steel; both the large holes and the small holes on the surface of the stainless steel can be loaded with drugs, which can achieve the purpose of double drug loading, and can realize slow drug loading. release effect. When the stainless steel provided by the present invention can be used in drug-eluting stents, the large pores can carry the first drug mixed with the drug carrier, the small pores only carry the second drug, and the first drug in the large pores can be loaded with the drug carrier The degradation of the stent is gradually released to achieve the effect of sustained release, and the second drug in the small hole can be released faster than the first drug to relieve the symptoms of inflammation and other reactions caused by the initial implantation of the stent in the body. The drugs in the large and small holes of the stainless steel can better meet the different needs for drugs in the initial and later stages of stent implantation.

Description

A kind of stainless steel and its preparation method and drug-eluting stent

technical field

The invention relates to the technical field of stainless steel, in particular to a stainless steel and a preparation method thereof and a drug-eluting stent.

Background technique

316L stainless steel is widely used in orthopedic implants, dental implants and coronary stents and other medical fields due to its good biocompatibility, mechanical properties and corrosion resistance. The nano-stacked pore structure is prepared on the surface of 316L stainless steel, which is beneficial to the loading of drugs and the effect of sustained drug release.

Drug-eluting stents can significantly reduce the rate of vascular restenosis. Functional drugs such as the immunosuppressive drug rapamycin (RAPA), the antiproliferative drug paclitaxel (PTX), the anti-inflammatory drug dexamethasone (DXM), and the antithrombotic drug Hirudin are usually used to load the drug into the In the metal matrix of the stent, when the stent is implanted into the diseased part of the body, it can achieve precise drug release in the local diseased part, and achieve the purpose of inhibiting the proliferation of smooth muscle cells, inflammation, and thrombosis.

Among the existing technologies, "Controlled drug release using nanoporous anodized aluminum oxide on stent" (Kang, HJ, Kim, DJ, Park, SJ, Yoo, JB, Ryu, YS. Controlled drug release using nanoporous anodicaluminum oxide on stent[ C] Thin Solid Films 515 (2007) 5184–5187) on the surface of 316L stainless steel by coating method to make nanoporous alumina layer on the surface to achieve the purpose of drug loading, but the drug can not achieve the effect of sustained release, and alumina nanoporous There is a problem that the bonding force between the layer and the base stainless steel is insufficient, and the coating is easy to fall off. "Using Composite Polylactic Acid (Lactic-Co-Glycolic Acid) Sustained Release Ibuprofen/Titanium Dioxide Nanotubes on the Surface of Titanium Implants" ( Jia,HY , Kerr.LL Sustained Ibuprofen Release Using Composite Poly(Lactic-co-GlycolicAcid) /Titanium Dioxide Nanotubes from Ti Implant Surface[J].Journal of Pharmaceutical Sciences,Vol.102,2341–2348(2013)) uses polymer loaded drug, the sustained release effect is good, but there is the problem of late thrombosis, and during the operation The polymer drug coating peels off easily.

SUMMARY OF THE INVENTION

The invention provides a stainless steel and a preparation method thereof and a drug-eluting stent, which solve the problems of insufficient binding force between the drug coating and the substrate and easy to fall off.

Its specific technical solutions are as follows:

The invention provides a kind of stainless steel. Small holes and large holes are formed on the surface of the stainless steel in situ, and the large holes and the small holes are in a stacked hole structure in which the large holes are set over the small holes.

In the present invention, the large holes and small holes on the surface of the stainless steel are formed in situ, so there is no problem of insufficient bonding force between the coating and the substrate; both the large and small holes on the surface of the stainless steel can be loaded with drugs, so as to realize double drug loading. effect, and can achieve the effect of prolonging the drug release time.

In the present invention, the pore size ratio of the large pores to the small pores is (18:5)～(15:1), preferably (12:1), wherein the pore size of the small pores is 20nm～50nm, which is suitable for small pores. For molecular drug loading, the pore size of the macropore is 180nm-300nm, preferably 180nm-260nm.

The depth of the small holes is about 4 μm-5 μm, and the depth of the large holes is about 20 nm-45 nm. The macropore has a large pore size and a certain pore depth, which can improve the binding force between the degradable polymer drug carrier and the stainless steel.

In the present invention, the number of small pores is large and the pore size is suitable, so that the loading amount of the drug required by the clinic can be satisfied.

In the present invention, the stainless steel is preferably 316L stainless steel.

The present invention also provides a preparation method of stainless steel, comprising the following steps:

Step 1: use stainless steel as the anode and graphite as the cathode, and perform the first anodic oxidation in the first electrolyte to obtain stainless steel with a macroporous structure on the surface;

Step 2: Using the stainless steel with the macroporous structure on the surface as the anode and the graphite as the cathode, the second anodic oxidation is performed in the second electrolyte, and after annealing treatment, the stainless steel with the large pores and the small pores in the stacked pore structure is obtained ;

The first electrolyte is sodium dihydrogen phosphate aqueous solution, potassium dihydrogen phosphate aqueous solution electrolyte or phosphoric acid aqueous solution, preferably sodium dihydrogen phosphate aqueous solution;

The second electrolyte is an alcoholic solution of ammonium fluoride.

The purpose of the first anodic oxidation of the present invention is to obtain large pores on the surface of the stainless steel, and the purpose of the second anodic oxidation is to obtain small pores on the surface of the stainless steel, thereby obtaining a stacked-porous structure film with large pores and small pores.

In step 1 of the present invention, preferably a stainless steel sheet is used as the anode, and a graphite sheet is used as the cathode.

The stainless steel sheet needs to be pre-treated before the first anodization;

The pretreatment specifically includes: sandpaper grinding, cleaning, and electrochemical polishing of the stainless steel in sequence, and transparent glue encapsulating the back of the reaction surface.

The grinding is step-by-step grinding with 500#-1500# sandpaper; the cleaning is acetone, ethanol, and deionized water, respectively, under ultrasonic conditions for 10 minutes; in the electrochemical polishing, the polishing solution is a mixture of phosphoric acid and sulfuric acid liquid, the volume ratio is 3:2; in the polishing step, stainless steel is used as the anode, graphite is used as the cathode, the reaction time is 4min-6min, the stirring speed is 760r/min, the reaction temperature is 85℃, and the reaction current density is 30A/dm ² - 50A/dm ² .

In step 1 of the present invention, the concentration of the first electrolyte is 0.05mol/L-0.4mol/L, preferably 0.3mol/L;

The voltage of the first anodic oxidation is 20V-60V, preferably 30V, the time is 5min-40min, preferably 20min, the reaction temperature is 0°C to 20°C, preferably 0°C, and the stirring speed is 350r/min.

The first anodic oxidation of the present invention can only generate macroporous structure in situ on the stainless steel surface under specific process parameters.

In step 2 of the present invention, the solvent in the alcoholic solution of ammonium fluoride of the second electrolyte is preferably ethylene glycol, and the concentration of the alcoholic solution of ammonium fluoride is 0.05-0.15mol/L, preferably 0.15mol/L. L;

The voltage of the second anodic oxidation is 40-60V, preferably 60V, the time is 10min-60min, preferably 10min, the reaction temperature is 0-35°C, preferably 20°C, and the stirring speed is 600r/min;

The annealing treatment is preferably carried out in an atmosphere of nitrogen or an inert gas, the inert gas is preferably argon, the annealing temperature is 350°C to 400°C, the holding time is 40min to 60min, and the heating time and the cooling time are 5°C ~6°C/min.

The second anodic oxidation of the present invention can only generate a small pore structure on the surface of the stainless steel in situ under specific process parameters, and then form a stacked pore structure with the large pores.

The present invention also provides the application of the above stainless steel or the stainless steel prepared by the above preparation method in the preparation of a drug-eluting stent.

The present invention also provides a drug-eluting stent, comprising: the above-mentioned stainless steel or the stainless steel prepared by the above-mentioned preparation method, a drug carrier and a first drug loaded in the large pores on the surface of the stainless steel, and a drug loaded on the surface of the stainless steel A second drug in the small hole.

In the drug-eluting stent provided by the present invention, stainless steel is used as the matrix, and the price is low. The drug carrier in the large pores of stainless steel can make the first drug achieve the effect of slow release, so as to achieve the best therapeutic effect. When the stent is implanted in the body, reactions such as inflammation will occur in the body. Since the second drug in the small hole is not mixed with a drug carrier, the second drug will be released faster to relieve inflammation. The two drugs in drug-eluting stents better meet the different needs of drugs in the initial and later stages of stent implantation.

In the present invention, the degradable polymer is preferably chitosan or poly(lactic-co-glycolic acid) (PLGA), more preferably PLGA75/25;

The first drug is a drug for preventing vascular restenosis, preferably rapamycin and/or paclitaxel;

The second drug is an anti-inflammatory drug, preferably dexamethasone.

In the present invention, the macroporous structure can improve the binding force between the polymer and the stent, and at the same time reduce the burst release of the two drugs, and the first drug can be released with the degradation of the degradable polymer. In the stacked-hole structure of stainless steel, only the large pores contain polymer, and the amount of polymer is small, which can reduce the probability of late thrombosis.

In the present invention, the mass ratio of the first drug to the drug carrier is (2:8) to (4:6), preferably 3:7.

The preparation method of the drug-eluting stent of the present invention comprises the following steps:

1) prepare the first medicine solution: after the first medicine is mixed with the medicine carrier, it is dissolved in the solvent to obtain the first medicine solution;

2) preparing the second drug solution: dissolving the second drug in the solvent to obtain the second drug solution;

3) The second drug solution is loaded into the pores of the stacked pore structure by dip coating method, and after drying, the first drug solution is loaded into the large pores of the stacked pore structure by the dip coating method, and dried to obtain the drug Elution stent.

In step 1) of the present invention, the silicone rubber is preferably 706 silicone rubber.

In step 1) of the present invention, the solvent is preferably 1,4-dioxane; in the first drug solution, the mass concentration of the drug carrier is 1% to 2%, preferably 1%.

In step 2) of the present invention, the solvent is preferably ethanol, and the concentration of the second drug solution is 1 mg/mL-2 mg/mL, preferably 1 mg/mL.

In step 3) of the present invention, after the second drug solution is loaded into the small hole by dip coating, it is dried, and the operation is repeated. After the loading of the second drug reaches the preset target value, the first drug solution is added. The dipping coating of the second drug solution is dipped in the macropore according to the preset value and dried; the drying of the second drug solution is preferably vacuum drying in a vacuum drying oven at 37 ° C for 1 h, and the drying of the first drug solution is preferably at room temperature. Dry for 24h, and then dry in a drying oven at 37°C for 2h.

As can be seen from the above technical solutions, the present invention has the following advantages:

The invention provides a kind of stainless steel. Small holes and large holes are formed on the surface of the stainless steel in situ, and the large holes and the small holes are in a stacked hole structure in which the large holes are set over the small holes.

The large holes and small holes on the surface of the stainless steel provided by the invention are generated in situ, and are closely combined with the stainless steel; both the large holes and the small holes on the surface of the stainless steel can be loaded with drugs, the effect of double drug loading can be realized, and the release of the drugs can be prolonged. time purpose. When the stainless steel provided by the present invention can be used in drug-eluting stents, the large pores can carry the first drug mixed with the drug carrier, the small pores only carry the second drug, and the first drug in the large pores can be loaded with the drug carrier The degradation of the stent is gradually released to achieve the effect of sustained release, and the second drug in the small hole can be released faster than the first drug to relieve the symptoms of inflammation and other reactions caused by the initial implantation of the stent in the body. The drugs in the large and small holes of stainless steel can better meet the different needs of drugs in the early and later stages of stent implantation.

Description of drawings

In order to explain the embodiments of the present invention or the technical solutions in the prior art more clearly, the following briefly introduces the accompanying drawings that need to be used in the description of the embodiments or the prior art. Obviously, the accompanying drawings in the following description are only These are some embodiments of the present invention. For those of ordinary skill in the art, other drawings can also be obtained based on these drawings without any creative effort.

Fig. 1 is the high magnification scanning electron microscope image of the stainless steel surface of the stacked hole structure provided in the embodiment 3 of the present invention;

Fig. 2 is the low magnification scanning electron microscope image of the stainless steel surface of the stacked hole structure provided in Example 3 of the present invention;

3 is a schematic diagram of two drug-eluting release curves of the drug-eluting stent provided in Example 3 of the present invention;

Fig. 4 is the high magnification scanning electron microscope picture of the stainless steel anodic oxidation surface that the comparative example 1 of the present invention provides;

5 is a low-magnification scanning electron microscope image of the anodized surface of the stainless steel provided in Comparative Example 2 of the present invention.

Detailed ways

In order to make the purpose, features and advantages of the present invention more obvious and understandable, the technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the embodiments described below are only a part of the implementation of the present invention. examples, but not all examples. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts shall fall within the protection scope of the present invention.

The water described in the embodiments of the present invention is deionized water.

Example 1

This example is the preparation of stainless steel with stacked hole structure

Anodizing process: use the encapsulated stainless steel sheet as the anode, graphite as the cathode (50mm×130mm), the pole spacing is 35mm, the cathode area is larger than that of the anode, and the temperature is controlled by a low-temperature constant temperature reaction bath, and the magnetic stirring speed is 600r/min , to ensure uniform mass transfer and diffusion of reactants during anodization. Anodizing is carried out in two steps.

The first step anodization: the electrolyte adopts sodium dihydrogen phosphate/water system, wherein the concentration of sodium dihydrogen phosphate is 0.3mol/L, the constant pressure method is used, the voltage is 30V, the temperature of the constant temperature water bath is 0℃, and the magnetic stirring speed is adjusted to 350r/min, anodizing time is 20min;

The second step of anodic oxidation: the electrolyte adopts ammonium fluoride/ethylene glycol organic electrolyte system, in which the concentration of ammonium fluoride is 0.05M, the constant voltage method is used, the voltage is 40V, the temperature of the constant temperature water bath is 35℃, and the anodic oxidation time is 10min , adjust the magnetic stirring speed to 600r/min. After the two-step anodic oxidation reaction was completed, the prepared samples were stored in a small beaker containing ethanol, and ultrasonically cleaned in a cleaning tank for 10 min to remove the electrolyte on the surface of the samples.

The anodized sample was annealed in an argon atmosphere. The annealing temperature was 350 °C, the holding time was 40 min, and the heating time and cooling time were 5 °C/min to obtain a stainless steel with a stacked-hole structure.

Microscopic morphology observation: The surface morphology of the sample was observed using a field emission scanning electron microscope (Hitachi SU8010). The macropores on the stainless steel surface were irregular polygonal, and the small pores inside the macropores were honeycomb-like and the pore size was 20nm-60nm. , the overall regular and neat, a network-like structure.

Example 2

This example is the preparation of stainless steel with stacked hole structure

Anodizing process: use the encapsulated stainless steel sheet as the anode, graphite as the cathode (50mm×130mm), the pole spacing is 35mm, the cathode area is larger than that of the anode, and the temperature is controlled by a low-temperature constant temperature reaction bath, and the magnetic stirring speed is 600r/min , to ensure uniform mass transfer and diffusion of reactants during anodization. Anodizing is carried out in two steps.

The first step anodization: the electrolyte adopts sodium dihydrogen phosphate/water system, wherein the concentration of sodium dihydrogen phosphate is 0.3mol/L, the constant pressure method is used, the voltage is 30V, the temperature of the constant temperature water bath is 0℃, and the magnetic stirring speed is adjusted to 350r/min, anodizing time is 20min;

The second step of anodic oxidation: the electrolyte adopts ammonium fluoride/ethylene glycol organic electrolyte system, in which the concentration of ammonium fluoride is 0.10M, the constant voltage method is used, the voltage is 40V, the temperature of the constant temperature water bath is 0℃, and the anodic oxidation time is 60min , adjust the magnetic stirring speed to 600r/min. After the two-step anodic oxidation reaction was completed, the prepared samples were stored in a small beaker containing ethanol, and ultrasonically cleaned in a cleaning tank for 10 min to remove the electrolyte on the surface of the samples.

The anodized sample was annealed in an argon atmosphere. The annealing temperature was 350 °C, the holding time was 40 min, and the heating time and cooling time were 5 °C/min to obtain a stainless steel with a stacked-hole structure.

Microscopic morphology observation: The surface morphology of the sample was observed using a field emission scanning electron microscope (Hitachi SU8010). 50nm, the overall regular and neat, like a network structure.

Example 3

This example is the preparation of stainless steel stacked hole structure

Anodizing process: use the encapsulated stainless steel sheet as the anode, graphite as the cathode (50mm×130mm), the pole spacing is 35mm, the cathode area is larger than that of the anode, and the temperature is controlled by a low-temperature constant temperature reaction bath, and the magnetic stirring speed is 600r/min , to ensure uniform mass transfer and diffusion of reactants during anodization. Anodizing is carried out in two steps.

The first step anodization: the electrolyte adopts sodium dihydrogen phosphate/water system, wherein the concentration of sodium dihydrogen phosphate is 0.3mol/L, the constant pressure method is used, the voltage is 30V, the temperature of the constant temperature water bath is 0℃, and the magnetic stirring speed is adjusted to 350r/min, anodizing time is 20min;

The second step of anodic oxidation: the electrolyte adopts ammonium fluoride/ethylene glycol organic electrolyte system, in which the concentration of ammonium fluoride is 0.15M, the constant voltage method is used, the voltage is 60V, the temperature of the constant temperature water bath is 20℃, and the anodic oxidation time is 10min , adjust the magnetic stirring speed to 600r/min. After the two-step anodic oxidation reaction was completed, the prepared samples were stored in a small beaker containing ethanol, and ultrasonically cleaned in a cleaning tank for 10 min to remove the electrolyte on the surface of the samples.

The anodized sample was annealed in an argon atmosphere. The annealing temperature was 350°C, the holding time was 40min, and the heating time and cooling time were 5°C/min to obtain a stainless steel with a stacked hole structure.

Microscopic morphology observation: The surface morphology of the samples was observed using a field emission scanning electron microscope (Hitachi SU8010). As shown in Figure 1 and Figure 2, the large pores on the surface of the stainless steel are elliptical, and the small pores inside the large pores are relatively regular honeycombs with a diameter of 30nm-50nm.

Example 4

This example is the preparation of stainless steel with stacked hole structure

Anodizing process: use the encapsulated stainless steel sheet as the anode, graphite as the cathode (50mm×130mm), the pole spacing is 35mm, the cathode area is larger than that of the anode, and the temperature is controlled by a low-temperature constant temperature reaction bath, and the magnetic stirring speed is 600r/min , to ensure uniform mass transfer and diffusion of reactants during anodization. Anodizing is carried out in two steps.

The first step anodization: the electrolyte adopts sodium dihydrogen phosphate/water system, wherein the concentration of sodium dihydrogen phosphate is 0.3mol/L, the constant pressure method is used, the voltage is 30V, the temperature of the constant temperature water bath is 0℃, and the magnetic stirring speed is adjusted to 350r/min, anodizing time is 20min;

The second step of anodic oxidation: the electrolyte adopts ammonium fluoride/ethylene glycol organic electrolyte system, in which the concentration of ammonium fluoride is 0.10M, the constant voltage method is used, the voltage is 40V, the temperature of the constant temperature water bath is 35℃, and the anodic oxidation time is 10min , adjust the magnetic stirring speed to 600r/min. After the two-step anodic oxidation reaction was completed, the prepared samples were stored in a small beaker containing ethanol, and ultrasonically cleaned in a cleaning tank for 10 min to remove the electrolyte on the surface of the samples.

The anodized sample was annealed in an argon atmosphere. The annealing temperature was 350°C, the holding time was 40min, and the heating time and cooling time were 5°C/min to obtain a stainless steel with a stacked hole structure.

Microscopic morphology observation: The surface morphology of the sample was observed using a field emission scanning electron microscope (Hitachi SU8010). The large pores on the surface of the stainless steel were irregular, and the small pores inside the large pores were mostly connected. like structure.

Example 5

This example is the preparation of stainless steel with stacked hole structure

Anodizing process: use the encapsulated stainless steel sheet as the anode, graphite as the cathode (50mm×130mm), the pole spacing is 35mm, the cathode area is larger than that of the anode, and the temperature is controlled by a low-temperature constant temperature reaction bath, and the magnetic stirring speed is 600r/min , to ensure uniform mass transfer and diffusion of reactants during anodization. Anodizing is carried out in two steps.

The first step anodization: the electrolyte adopts sodium dihydrogen phosphate/water system, wherein the concentration of sodium dihydrogen phosphate is 0.3mol/L, the constant pressure method is used, the voltage is 30V, the temperature of the constant temperature water bath is 0℃, and the magnetic stirring speed is adjusted to 350r/min, anodizing time is 20min;

The second step of anodic oxidation: the electrolyte adopts ammonium fluoride/ethylene glycol organic electrolyte system, in which the concentration of ammonium fluoride is 0.05M, the constant voltage method is used, the voltage is 40V, the temperature of the constant temperature water bath is 35℃, and the anodic oxidation time is 15min , adjust the magnetic stirring speed to 600r/min. After the two-step anodic oxidation reaction was completed, the prepared samples were stored in a small beaker containing ethanol, and ultrasonically cleaned in a cleaning tank for 10 min to remove the electrolyte on the surface of the samples.

The anodized sample was annealed in an argon atmosphere. The annealing temperature was 350°C, the holding time was 40min, and the heating time and cooling time were 5°C/min to obtain a stainless steel with a stacked hole structure.

Microscopic morphology observation: The surface morphology of the sample was observed using a field emission scanning electron microscope (Hitachi SU8010). The large pores on the surface of the stainless steel were irregular polygonal, and the small pores inside the large pores were honeycomb-like and some small pores were interconnected. Connections, the overall regularity and cleanliness, in a network-like structure.

Example 6

The preparation of the drug-eluting stent specifically includes the following steps:

1) Use a 10mm×10mm square 706 silicone rubber to circle a 10mm×10mm square fixed area on the surface of the stainless steel stacked hole structure of Example 3, and wait for the silicone rubber to dry for later use.

2) Preparation of rapamycin solution: after mixing rapamycin and degradable polymer PLGA70/25 in a mass ratio of 3:7, the degradable polymer with a final concentration of 1 wt % is dissolved in 1,4-diol. In oxane, slowly stir to obtain rapamycin solution;

3) Preparation of dexamethasone solution: dissolve dexamethasone in ethanol and stir slowly to obtain 1 mg/mL dexamethasone solution;

4) Use the dip coating method to load the dexamethasone solution into the small holes in the area surrounded by the silicone rubber, and vacuum dry it at 37°C for 1 hour. When the dexamethasone loading value is 100 μg, continue to use the dip coating method to apply the first type of dexamethasone solution. The drug solution was loaded into the large pores in the area surrounded by the silicone rubber, and when the rapamycin value was 150 μg, it was dried at room temperature for 24 hours, and then dried in a vacuum drying oven at 37°C for 2 hours to obtain a drug-eluting stent.

Step-by-step release process: The drug-loaded samples were placed in a centrifuge tube filled with phosphate buffered saline (PBS), and then the drug release study was carried out in a constant temperature incubator at a culture temperature of 37°C and a step-by-step release time interval. For 1h, 1h, 2h, 3h, 12h, 24h, 24h, 77h, 97h, 168h, 168h, each time an equal amount of new PBS solution is replaced, the PBS solution in the original centrifuge tube needs to be retained for detection. Ultraviolet spectrophotometer (UV) completed. As shown in Figure 3, the sustained-release effects of dexamethasone and rapamycin are good, and the drugs can be continuously released for more than three weeks.

Comparative Example 1

This comparative example 1 is the preparation of stainless steel

Anodizing process: use the encapsulated stainless steel sheet as the anode, graphite as the cathode (50mm×130mm), the pole spacing is 35mm, the cathode area is larger than that of the anode, and the temperature is controlled by a low-temperature constant temperature reaction bath, and the magnetic stirring speed is 600r/min , to ensure uniform mass transfer and diffusion of reactants during anodization. Anodizing is carried out in two steps.

The first step anodization: the electrolyte adopts sodium dihydrogen phosphate/water system, wherein the concentration of sodium dihydrogen phosphate is 0.3mol/L, the constant pressure method is used, the voltage is 30V, the temperature of the constant temperature water bath is 0℃, and the magnetic stirring speed is adjusted to 350r/min, anodizing time is 20min;

The second step of anodic oxidation: the electrolyte adopts ammonium fluoride/ethylene glycol organic electrolyte system, in which the concentration of ammonium fluoride is 0.15M, the constant voltage method is used, the voltage is 40V, the temperature of the constant temperature water bath is 35℃, and the anodic oxidation time is 15min , adjust the magnetic stirring speed to 600r/min. After the two-step anodic oxidation reaction was completed, the prepared samples were stored in a small beaker containing ethanol, and ultrasonically cleaned in a cleaning tank for 10 min to remove the electrolyte on the surface of the samples.

The anodized sample was annealed in an argon atmosphere, the annealing temperature was 350 °C, the holding time was 40 min, and the heating time and cooling time were 5 °C/min to obtain stainless steel.

Compared with Example 1, the concentration of the electrolyte in the second step of anodic oxidation in this comparative example increases, and the anodic oxidation time increases, which leads to excessive corrosion of the stainless steel surface, the macroporous structure is completely corroded, and the small pore structure is not regular enough.

Comparative Example 2

This comparative example 2 is the preparation of stainless steel

Anodizing process: use the encapsulated stainless steel sheet as the anode, graphite as the cathode (50mm×130mm), the pole spacing is 35mm, the cathode area is larger than that of the anode, and the temperature is controlled by a low-temperature constant temperature reaction bath, and the magnetic stirring speed is 600r/min , to ensure uniform mass transfer and diffusion of reactants during anodization. Anodizing is carried out in two steps.

The first step of anodic oxidation: the electrolyte adopts sodium dihydrogen phosphate/water (the water mentioned in the text is deionized water) system, wherein the concentration of sodium dihydrogen phosphate is 0.3mol/L, the constant voltage method is adopted, and the voltage is 30V, The temperature of the constant temperature water bath is 0°C, the magnetic stirring speed is adjusted to 350r/min, and the anodizing time is 20min;

The second step of anodic oxidation: the electrolyte adopts ammonium fluoride/ethylene glycol organic electrolyte system, in which the concentration of ammonium fluoride is 0.15M, the constant voltage method is used, the voltage is 40V, the temperature of the constant temperature water bath is 20℃, and the anodic oxidation time is 10min , adjust the magnetic stirring speed to 600r/min. After the two-step anodic oxidation reaction was completed, the prepared samples were stored in a small beaker containing ethanol, and ultrasonically cleaned in a cleaning tank for 10 min to remove the electrolyte on the surface of the samples.

The anodized sample was annealed in an argon atmosphere, the annealing temperature was 350 °C, the holding time was 40 min, and the heating time and cooling time were 5 °C/min to obtain stainless steel.

Compared with Example 3, this comparative example lowers the value of the reaction voltage, resulting in that the structure of the generated pores is not regular enough, and the pore sizes are different.

As mentioned above, the above embodiments are only used to illustrate the technical solutions of the present invention, but not to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those of ordinary skill in the art should understand: The technical solutions described in the embodiments are modified, or some technical features thereof are equivalently replaced; and these modifications or replacements do not make the essence of the corresponding technical solutions depart from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims (10)

1. Stainless steel, characterized in that, the surface of the stainless steel generates small holes and big holes in situ, the big holes and the small holes are in a stacked hole structure of big holes and small holes;

the aperture ratio of the big holes to the small holes is (18:5) - (15: 1).

2. The stainless steel according to claim 1, wherein the depth of the small pores is 4 to 5 μm, and the depth of the large pores is 20 to 45 nm.

3. The stainless steel of claim 1, wherein the stainless steel is 316L stainless steel.

4. A method for preparing stainless steel is characterized by comprising the following steps:

step 1: carrying out first anodic oxidation in a first electrolyte by taking stainless steel as an anode and graphite as a cathode to obtain stainless steel with a surface containing a macroporous structure;

step 2: taking the stainless steel with the surface containing the macroporous structure as an anode and graphite as a cathode, carrying out secondary anodic oxidation in a second electrolyte, and annealing to obtain the stainless steel with the macropore and the small pore and the overlapped pore structure;

the first electrolyte is sodium dihydrogen phosphate aqueous solution, potassium dihydrogen phosphate aqueous solution electrolyte or phosphoric acid aqueous solution;

the second electrolyte is an alcoholic solution of ammonium fluoride.

5. The preparation method according to claim 4, wherein the voltage of the first anodic oxidation is 20V-60V, the time is 5min-40min, the reaction temperature is 0-20 ℃, and the stirring speed is 350 r/min;

the concentration of the first electrolyte is 0.05mol/L-0.4 mol/L.

6. The preparation method according to claim 4, wherein the voltage of the second anodic oxidation is 40-60V, the time is 10min-60min, the reaction temperature is 0-35 ℃, and the stirring speed is 600 r/min;

the concentration of the second electrolyte is 0.05-0.15 mol/L.

7. Use of a stainless steel according to any one of claims 1 to 3 or a stainless steel produced by the method of any one of claims 4 to 6 in the manufacture of a drug eluting stent.

8. A drug eluting stent, comprising: the stainless steel of any one of claims 1 to 3 or the stainless steel prepared by the preparation method of any one of claims 4 to 6, a drug carrier and a first drug loaded in the large pores on the surface of the stainless steel, and a second drug loaded in the small pores on the surface of the stainless steel.

9. The drug-eluting stent of claim 8, wherein the drug carrier is a degradable polymer;

the first medicament is a medicament for preventing vascular restenosis;

the second drug is an anti-inflammatory drug.

10. The drug-eluting stent of claim 8, wherein a mass ratio of the first drug to the drug carrier is (2:8) - (4: 6).

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