SPIRAL COATED STENT WITH CONTROLLABLE GRADIENT DEGRADATION, PREPARATION METHOD THEREOF AND APPLICATION THEREOF

Abstract

Disclosed are a spiral coated stent with controllable gradient degradation, a preparation method thereof and an application thereof. The spiral coated stent with controllable gradient degradation is composed of a degradable medical polyurethane and a degradable magnesium alloy material, wherein the degradable medical polyurethane contains a following chemical structure: PCL-PEG-PCL, wherein a molecular weight of the PEG is 200 to 1,000 and the molecular weight of the PCL is 200 to 10,000, and the degradable magnesium alloy material is of a spiral stent structure; and physical properties of the spiral coated stent with controllable gradient degradation need to satisfy the following technical parameters that: a breaking strength needs to be no less than 1 N, a pressure resistance needs to be no less than 2 N, and a degradation characteristic of the magnesium alloy after surface treatment shows gradient degradation with different time.

Claims

1. A spiral coated stent with controllable gradient degradation, comprising a degradable medical polyurethane and a degradable magnesium alloy material, wherein a soft segment of the degradable medical polyurethane contains a following chemical structure: PCL-PEG-PCL, wherein a molecular weight of the PEG is 200 to 1,000, and a molecular weight of the PCL is 200 to 10,000; the degradable magnesium alloy material is of a spiral structure; and physical properties of the spiral coated stent with controllable gradient degradation need to satisfy the following technical parameters that: a breaking strength needs to be no less than 1 N, a pressure resistance needs to be no less than 2 N, and a degradation characteristic of the magnesium alloy after surface treatment shows gradient degradation with different time after soaking in an aqueous solution.

2. The spiral coated stent with controllable gradient degradation according to claim 1, comprising the degradable medical polyurethane and the degradable magnesium alloy material, wherein a hard segment of the degradable medical polyurethane is L-lysine diisocyanate, and the soft segment contains the following chemical structure: PCL-PEG-PCL, wherein the molecular weight of the PEG is 200 to 1,000, and the molecular weight of the PCL is 200 to 5,000; the degradable magnesium alloy material is of a spiral structure; and the physical properties of the spiral coated stent with controllable gradient degradation need to satisfy the following technical parameters that: the breaking strength needs to be no less than 1 N, the pressure resistance needs to be no less than 2 N, and the degradation characteristic of the magnesium alloy after surface treatment shows gradient degradation with different time after soaking in the aqueous solution; and a weight percentage of the degradable medical polyurethane to the degradable magnesium alloy material is 10% to 99%:1% to 90%.

3. The spiral coated stent with controllable gradient degradation according to claim 2, comprising the degradable medical polyurethane and the degradable magnesium alloy material, wherein the hard segment of the degradable medical polyurethane is L-lysine diisocyanate, and the soft segment contains the following chemical structure: PCL-PEG-PCL, wherein the molecular weight of the PEG is 200 to 600, and the molecular weight of the PCL is 300 to 3,500; and a chain extender is selected from one of propylene glycol and diamine or diaminelike; the degradable magnesium alloy material is of a spiral structure, which can be woven in a single-strand spiral or multi-strand spiral manner; and the physical properties of the spiral coated stent with controllable gradient degradation need to satisfy the following technical parameters that: the breaking strength needs to be no less than 1 N, an elongation at break needs to be no less than 50%, the pressure resistance needs to be no less than 2 N, and the degradation characteristic of the magnesium alloy after surface treatment shows gradient degradation with different time after soaking in an aqueous solution; and the weight percentage of the degradable medical polyurethane to the degradable magnesium alloy material is 30% to 99%:1% to 70%.

4. The spiral coated stent with controllable gradient degradation according to claim 1, wherein the degradable polyurethane is prepared by one of the following preparation methods: first method: using CL with different proportions and PEG with a molecular weight of 200 to 1,000 to synthesize a linear polycaprolactone diol, reacting the product with L-lysine diisocyanate, using propylene glycol or amino acid diamine as a chain extender and using organic tin or organic bismuth as a catalyst, and reacting to obtain the medical polyurethane used for the stent of the disclosure; second method: using PDO and different diols to synthesize a linear PPDO poly diol, reacting the product with different diisocyanates, using different diols, amino acid diamines or diamines as chain extenders and using organic tin or organic bismuth as a catalyst, and reacting to obtain the medical polyurethane, which can be further added as a stent coating material in order to improve a degradation performance of the stent; third method: using LA and GA with different molecular weights initiated by micromolecule diols for monomerization or copolymerization to obtain polymer diol, adipic acid polyester diol and oxalic acid polyester diol which are used as soft chains and reacted with LDI and different micromolecule diols or diamines, and using organic tin or organic bismuth as a catalyst, and reacting to obtain the medical polyurethane, which can be further added as a stent coating material in order to improve the degradation performance of the stent; and fourth method: using hydroxyl-terminated polydimethylsiloxane as a soft segment and reacting with LDI and micromolecule diol or diamine, and using organic tin or organic bismuth as a catalyst to form an organosilicon-polyurethane block copolymer composed of softs segment and hard segments alternately, which can be further added as a stent coating material in order to improve the degradation performance of the stent.

5. The spiral coated stent with controllable gradient degradation according to claim 2, wherein the degradable polyurethane is prepared by one of the following preparation methods: first method: using CL with different proportions and PEG with a molecular weight of 200 to 1,000 to synthesize a linear polycaprolactone diol, reacting the product with L-lysine diisocyanate, using propylene glycol or amino acid diamine as a chain extender and using organic tin or organic bismuth as a catalyst, and reacting to obtain the medical polyurethane used for the stent of the disclosure; second method: using PDO and different diols to synthesize a linear PPDO poly diol, reacting the product with different diisocyanates, using different diols, amino acid diamines or diamines as chain extenders and using organic tin or organic bismuth as a catalyst, and reacting to obtain the medical polyurethane, which can be further added as a stent coating material in order to improve a degradation performance of the stent; third method: using LA and GA with different molecular weights initiated by micromolecule diols for monomerization or copolymerization to obtain polymer diol, adipic acid polyester diol and oxalic acid polyester diol which are used as soft chains and reacted with LDI and different micromolecule diols or diamines, and using organic tin or organic bismuth as a catalyst, and reacting to obtain the medical polyurethane, which can be further added as a stent coating material in order to improve the degradation performance of the stent; and fourth method: using hydroxyl-terminated polydimethylsiloxane as a soft segment and reacting with LDI and micromolecule diol or diamine, and using organic tin or organic bismuth as a catalyst to form an organosilicon-polyurethane block copolymer composed of softs segment and hard segments alternately, which can be further added as a stent coating material in order to improve the degradation performance of the stent.

6. The spiral coated stent with controllable gradient degradation according to claim 3, wherein the degradable polyurethane is prepared by one of the following preparation methods: first method: using CL with different proportions and PEG with a molecular weight of 200 to 1,000 to synthesize a linear polycaprolactone diol, reacting the product with L-lysine diisocyanate, using propylene glycol or amino acid diamine as a chain extender and using organic tin or organic bismuth as a catalyst, and reacting to obtain the medical polyurethane used for the stent of the disclosure; second method: using PDO and different diols to synthesize a linear PPDO poly diol, reacting the product with different diisocyanates, using different diols, amino acid diamines or diamines as chain extenders and using organic tin or organic bismuth as a catalyst, and reacting to obtain the medical polyurethane, which can be further added as a stent coating material in order to improve a degradation performance of the stent; third method: using LA and GA with different molecular weights initiated by micromolecule diols for monomerization or copolymerization to obtain polymer diol, adipic acid polyester diol and oxalic acid polyester diol which are used as soft chains and reacted with LDI and different micromolecule diols or diamines, and using organic tin or organic bismuth as a catalyst, and reacting to obtain the medical polyurethane, which can be further added as a stent coating material in order to improve the degradation performance of the stent; and fourth method: using hydroxyl-terminated polydimethylsiloxane as a soft segment and reacting with LDI and micromolecule diol or diamine, and using organic tin or organic bismuth as a catalyst to form an organosilicon-polyurethane block copolymer composed of softs segment and hard segments alternately, which can be further added as a stent coating material in order to improve the degradation performance of the stent.

7. The spiral coated stent with controllable gradient degradation according to claim 1, wherein the degradable medical polyurethane material can further comprise the soft segment which is a polymer diol obtained by copolymerization of one or two of LA, GA, CL, PDO and adipic anhydride with a micromolecule diol as an initiator, and the chain extender is selected from micromolecule diol, diamine or diaminelike, and specifically selected from one or two of glycol, diglycol, tetraglycol, 1,3-propanediol, 1,4-butanediol, 1,6-hexanediol, 1,7-heptanediol, 1,8-octanediol, 1,9-nonanediol, 1,10-decanediol, ethylenediamine, propylene diamine, butanediamine, pentanediamine and amino acid diamine.

8. The spiral coated stent with controllable gradient degradation according to claim 2, wherein the degradable medical polyurethane material can further comprise the soft segment which is a polymer diol obtained by copolymerization of one or two of LA, GA, CL, PDO and adipic anhydride with a micromolecule diol as an initiator, and the chain extender is selected from micromolecule diol, diamine or diaminelike, and specifically selected from one or two of glycol, diglycol, tetraglycol, 1,3-propanediol, 1,4-butanediol, 1,6-hexanediol, 1,7-heptanediol, 1,8-octanediol, 1,9-nonanediol, 1,10-decanediol, ethylenediamine, propylene diamine, butanediamine, pentanediamine and amino acid diamine.

9. The spiral coated stent with controllable gradient degradation according to claim 3, wherein the degradable medical polyurethane material can further comprise the soft segment which is a polymer diol obtained by copolymerization of one or two of LA, GA, CL, PDO and adipic anhydride with a micromolecule diol as an initiator, and the chain extender is selected from micromolecule diol, diamine or diaminelike, and specifically selected from one or two of glycol, diglycol, tetraglycol, 1,3-propanediol, 1,4-butanediol, 1,6-hexanediol, 1,7-heptanediol, 1,8-octanediol, 1,9-nonanediol, 1,10-decanediol, ethylenediamine, propylene diamine, butanediamine, pentanediamine and amino acid diamine.

10. The spiral coated stent with controllable gradient degradation according to claim 1, comprising other polymer materials, wherein hydrophobic polymer materials comprise: one or two of polylactic acid, polycaprolactone, poly(p-dioxanone) and copolymers thereof, polytrimethylene carbonate, polylactic acid-trimethylene carbonate copolymer, polycaprolactone-trimethylene carbonate copolymer, polyglycolic acid and polylactic acid-glycolic acid copolymer, and a viscosity-average molecular weight of the biodegradable polymer material is 500 to 1,000,000, which is used for adjusting one of a softness and a hardness of the material; and hydrophilic polymer materials comprise: one of alginate, modified alginate and alginate degraded into hexosamine and N-acetylglucosamine, polyvinyl pyrrolidone series, starch grafted acrylonitrile, starch grafted hydrophilic monomer, polyacrylate, vinyl acetate copolymer, polyvinyl alcohol, modified polyvinyl alcohols, carboxymethyl cellulose, cellulose grafted acrylonitrile, cellulose grafted acrylate, cellulose xanthate grafted acrylate, cellulose grafted acrylamide, and epichlorohydrin cross-linked carboxymethyl cellulose; or one or a combination of a plurality of macromolecular antibacterial absorbent materials, various polyamino acids, chitosan and derivatives thereof, and polylysine.

11. The spiral coated stent with controllable gradient degradation according to claim 2, comprising other polymer materials, wherein hydrophobic polymer materials comprise: one or two of polylactic acid, polycaprolactone, poly(p-dioxanone) and copolymers thereof, polytrimethylene carbonate, polylactic acid-trimethylene carbonate copolymer, polycaprolactone-trimethylene carbonate copolymer, polyglycolic acid and polylactic acid-glycolic acid copolymer, and a viscosity-average molecular weight of the biodegradable polymer material is 500 to 1,000,000, which is used for adjusting one of a softness and a hardness of the material; and hydrophilic polymer materials comprise: one of alginate, modified alginate and alginate degraded into hexosamine and N-acetylglucosamine, polyvinyl pyrrolidone series, starch grafted acrylonitrile, starch grafted hydrophilic monomer, polyacrylate, vinyl acetate copolymer, polyvinyl alcohol, modified polyvinyl alcohols, carboxymethyl cellulose, cellulose grafted acrylonitrile, cellulose grafted acrylate, cellulose xanthate grafted acrylate, cellulose grafted acrylamide, and epichlorohydrin cross-linked carboxymethyl cellulose; or one or a combination of a plurality of macromolecular antibacterial absorbent materials, various polyamino acids, chitosan and derivatives thereof, and polylysine.

12. The spiral coated stent with controllable gradient degradation according to claim 1, wherein the degradable magnesium alloy material is selected from materials refined from various chemical elements harmless to a human body, specifically comprising one or a combination of two of high-purity magnesium, magnesium-iron alloy, magnesium-zinc alloy, magnesium-calcium alloy, and magnesium-aluminum alloy, preferably high-purity magnesium and magnesium-zinc alloy such as Mg—Nd—Zn—Zr, Mg—Zn—Mn, Mg—Zn—Zr, Mg—Zn—Mn—Se—Cu, and Mg—Zn binary alloy.

13. The spiral coated stent with controllable gradient degradation according to claim 2, wherein the degradable magnesium alloy material is selected from materials refined from various chemical elements harmless to a human body, specifically comprising one or a combination of two of high-purity magnesium, magnesium-iron alloy, magnesium-zinc alloy, magnesium-calcium alloy, and magnesium-aluminum alloy, preferably high-purity magnesium and magnesium-zinc alloy such as Mg—Nd—Zn—Zr, Mg—Zn—Mn, Mg—Zn—Zr, Mg—Zn—Mn—Se—Cu, and Mg—Zn binary alloy.

14. The spiral coated stent with controllable gradient degradation according to claim 1, comprising a contrast medium, specifically selected from one of zirconium dioxide, barium sulfate and iodine preparations.

15. The spiral coated stent with controllable gradient degradation according to claim 2, comprising a contrast medium, specifically selected from one of zirconium dioxide, barium sulfate and iodine preparations.

16. The spiral coated stent with controllable gradient degradation according to claim 3, comprising a contrast medium, specifically selected from one of zirconium dioxide, barium sulfate and iodine preparations.

17. A preparation method of a spiral coated stent with controllable gradient degradation, wherein, a first preparation method is as follows: (1) preparing a gradient degradable magnesium wire: completely soaking a round wire or a flat wire of a one-meter-long magnesium wire in a dipotassium hydrogen phosphate aqueous solution containing phytic acid with a certain concentration or a 5%-30% hydrofluoric acid solution, and lifting by 1 cm to 10 cm every 1 minute to 10 minutes to form a gradient passivation protective film, marking one end passivated for short time as B end and marking one end passivated for long time as A end; (2) crimping the degradable magnesium alloy wire processed in step (1) into a spiral pattern, dissolving a degradable medical polyurethane material or a composite material in an organic solvent to prepare a coating material, and evenly spraying the coating material on a surface of a stent through an electrostatic spinning nozzle in the continuous rotation process of the step (1) to manufacture the same into a coated composite stent with a thickness of 0.001 mm to 1 mm, and preferably 0.01 mm to 0.5 mm; and (3) dissolving a hydrophilic material in water to prepare a required concentration, and dip-coating or evenly spraying on the surface of the stent to manufacture the same into a water-soluble coating, which is convenient for clinicians to place and use; and a second preparation method is as follows: (1) preparing a gradient degradable magnesium wire: completely soaking a round wire or a flat wire of a one-meter-long magnesium wire in a dipotassium hydrogen phosphate aqueous solution containing phytic acid with a certain concentration or a 5%-30% hydrofluoric acid solution, and lifting by 1 cm to 10 cm every 1 minute to 10 minutes to form a gradient passivation protective film, marking one end passivated for short time as B end and marking one end passivated for long time as A end; (2) crimping the degradable magnesium alloy wire processed in step (1) into a spiral pattern, threading with tetrafluoroethylene or metal rod, spirally fixing the magnesium wire in a special grinding tool for manufacturing corrugated pipes according to a processing technology for manufacturing corrugated pipes, extruding the degradable medical polyurethane material with a tubule extruder to manufacture the same into a coated composite stent with a thickness of 0.001 mm to 1 mm, and preferably 0.01 mm to 0.5 mm; and (3) dissolving a hydrophilic material in water to prepare a required concentration, and dip-coating or evenly spraying on the surface of the stent to manufacture the same into a water-soluble coating, which is convenient for clinicians to place and use.

18. An application of a spiral coated stent with controllable gradient degradation for preparing various tract stents in vivo, specifically comprising: blood vessel, vein, gullet, biliary tract, trachea, bronchus, small intestine, large intestine, urethra, ureter or other segments similar to a tubular passage, such as vascular stents, tracheal stents, bronchial stents, urethral stents, gullet stents, biliary stents, ureteral stents, ureteral stenosis stents, stents for small intestine, stents for large intestine, laryngeal implants, bypass catheters or ileostomy.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0072] FIG. 1 is a schematic diagram of a single-strand spiral magnesium alloy stent;

[0073] FIG. 2 is a schematic diagram of a double-strand spiral magnesium alloy stent;

[0074] FIG. 3 is a schematic diagram of a multi-strand spiral magnesium alloy stent;

[0075] FIG. 4 is a schematic diagram of a degradable ureteral stent; and

[0076] FIG. 5 is a partial enlarged schematic diagram of the degradable ureteral stent.

DETAILED DESCRIPTION

[0077] Examples of magnesium alloy constituents selected in Embodiments 1 to 9 are as follows:

TABLE-US-00001 Zn Mn Se Sr Cu Ca Mg (wt %) (wt %) (wt %) (wt %) (wt %) (wt %) Zr (wt %) 1 0.2 0.5 Balance 2 4.0 0.9 0.1 0.5 Balance 3 1.2 Balance 4 0.2 1.5 0.2 Balance 5 0.1 0.1 0.1 Balance 6 1.2 0.2 Balance 7 5.0 — 0.1 0.2 0.1 Balance 8 4.0 0.2 0.1 Balance 9 4.2 0.1 0.2 — 0.1 Balance

Embodiment 1: Tracheal Coated Stent

[0078] A preparation process of the tracheal coated stent was as follows:

[0079] (1) weaving a degradable metal material (alloying constituent proportions were selected according to Table 2) wire into double-strand or multi-strand spiral stents (shapes as shown in FIG. 2 and FIG. 3), or cutting a magnesium alloy tube into a pattern or a porous shape of a commercially available vascular stent with spiral structure (the stent had a diameter of 6.5 mm, a length of 4 cm, and a wall thickness of 0.2 mm);

[0080] (2) polishing the stent prepared in step (1), soaking the stent in hydrofluoric acid with a mass percentage of 20% for 10 minutes, taking the stent out, and then washing with acetone, and drying;

[0081] (3) dissolving a degradable medical polyurethane material (polyurethane with PEG300 as an initiator, PCL diol as a soft segment and L-lysine diisocyanate as a hard segment, a number average molecular weight of 150,000 to 170,000, a breaking strength of 35 MPa, and an elongation at break of 350%) in a chloroform solvent to prepare a 8%15% solution; and

[0082] (4) dip-coating or evenly spraying the solution in (3) on the stent in (2) to manufacture the same into the coated stent (the stent had a tube wall thickness of 0.26 mm).

Embodiment 2: Drug-Loading Trachea Coated Stent

[0083] A preparation process of the drug-loading trachea coated stent was as follows:

[0084] (1) weaving a degradable material (alloying constituent proportions were selected according to Table 2) wire into double-strand or multi-strand spiral stents (shapes as shown in FIG. 2 and FIG. 3), or cutting a magnesium alloy tube into a pattern or a porous shape of a commercially available tracheal stent with spiral structure (the stent had a diameter of 7 mm, a length of 6 cm, and a wall thickness of 0.2 mm);

[0085] (2) polishing the stent prepared in step (1), soaking the stent in hydrofluoric acid with a mass percentage of 20% for 12 minutes, taking the stent out, and then washing with anhydrous acetone, and drying;

[0086] (3) dissolving a degradable medical polyurethane material (polyurethane with PEG300 as an initiator, PCL diol as a soft segment and L-lysine diisocyanate as a hard segment, a number average molecular weight of 190,000 to 210,000, a breaking strength of 35 MPa, and an elongation at break of 350%) in a chloroform solvent to prepare a 8%15% solution, and dissolving drugs (such as paclitaxel with a dosage range of 0.5 ug/mm2 to 10 ug/mm2) needed to treat malignant tumors or prevent restenosis in the prepared polyurethane chloroform solution;

[0087] (4) dip-coating or evenly spraying the solution in (3) on the stent in (2) to manufacture the same into the coated stent (the stent had a tube wall thickness of 0.28 mm); and:

[0088] (5) dip-coating or spraying the composite material prepared in (4) with a hydrophilic coating (such as aqueous solution made of chitosan, hyaluronic acid, collagen, cellulose, etc.), blowing-drying, polishing and grinding to manufacture the same into the coated stent.

Embodiment 3: Urethral Coated Stent

[0089] A preparation process of the urethral coated stent was as follows:

[0090] (1) weaving a degradable metallic material (alloying constituent proportions were selected according to Table 2) wire into double-strand or multi-strand spiral stents (shapes as shown in FIG. 2 and FIG. 3), or cutting a magnesium alloy tube into a pattern or a porous shape of a commercially available vascular stent with spiral structure (the stent had a diameter of 4.0 mm, a length of 2.5 cm, and a wall thickness of 0.16 mm);

[0091] (2) polishing the stent prepared in (1), soaking the stent in hydrofluoric acid with a mass percentage of 10% for 20 minutes to 30 minutes, taking the stent out, and then washing with acetone, and drying;

[0092] (3) dissolving a degradable medical polyurethane material (polyurethane with PEG600 as an initiator, PCL diol as a soft segment and L-lysine diisocyanate as a hard segment, a number average molecular weight of 60,000 to 80,000, a breaking strength of 35 MPa, and an elongation at break of 250%) in a chloroform solvent to prepare a 8%-15% solution for later use;

[0093] (4) dip-coating or evenly spraying the solution in (3) on the stent in (2) to manufacture the same into the coated stent (the stent had a tube wall thickness of 0.2 mm to 0.23 mm); and

[0094] (5) dip-coating or spraying the composite material prepared in (4) with a hydrophilic coating (such as aqueous solution made of chitosan, hyaluronic acid, collagen, cellulose, etc.), blowing-drying, polishing and grinding to manufacture the same into the coated stent.

Embodiment 4: In Vitro Degradation Experiments of the Three Stents According to the Embodiments

[0095] The stents obtained in the above embodiments were soaked in a PBS solution, the solution was changed once a week, and degradation of the stents was observed for a long time at 37° C. The results were as follows:

TABLE-US-00002 Before soaking 15 days 1 month 2 months Break- Compres- Break- Compres- Break- Compres- Break- 3 months 6 months Embodi- ing sive ing sive ing sive ing Compressive Breaking Compressive Breaking Compressive ment strength strength strength strength strength strength strength strength strength strength strength strength 1 3.5N 6.0N 3.5N 6.0N 3.0N 5.2N 2.5N 4.0N 2.0N 3.0N 1.5N 2.0N 2 3.3N 5.2N 3.1N 5.1N 3.0N 5.0N 3.0N 4.2N 2.5N 3.5N 1.9N 2.5N 3 3.0N 3.6N 2.8N 4.0N 2.5N 1.3N — — — — — —

Embodiment 5: First Preparation Method of Ureteral Stent with Gradient Degradation (Degradation Time Lasted for 1 to 2 Months)

[0096] 1. Preparation of a Gradient Degradable Magnesium Wire

[0097] A one-meter-long magnesium wire (0.2 mm to 0.3 mm in width, and 0.12 mm in thickness) was completely soaked in a 15 g/L dipotassium hydrogen phosphate aqueous solution containing 1.2 g/L phytic acid at about 60° C., and lifted by 5 cm every 2.5 minutes to form a gradient passivation protective film, one end passivated for short time was marked as B end and one end passivated for long time was marked as A end.

[0098] 2. Preparation of a Degradable Ureteral Stent

[0099] (1) The gradient degradable magnesium alloy wire (alloying constituent proportions were selected according to Table 9) processed was crimped into a single-strand spiral shape, with a pitch of 1.8 mm to 2.5 mm (as shown in FIG. 1) and a total stent length of 26 cm to 28 cm;

[0100] (2) a degradable medical polyurethane material (polyurethane with PEG400 as an initiator, PCL as a soft segment and L-lysine diisocyanate as a hard segment, a number average molecular weight of 50,000 to 70,000 (referring to Solution 9 in Embodiment 10 for specific synthesis method), a breaking strength of 20 MPa, and an elongation at break of 250%) was dissolved in a chloroform solvent to prepare a 8%-15% solution for later use;

[0101] (3) the solution in (2) was repeatedly dip-coated or evenly sprayed on the stent in (1) to manufacture the same into the coated stent (the stent had a tube wall thickness of 0.2 mm); (as shown in FIG. 4); and

[0102] (4) the composite material prepared in (3) was dip-coated or sprayed with a hydrophilic coating (such as aqueous solution made of PVA, PVP, and micromolecule hyaluronic acid, etc.), aired, polished and ground into the coated stent.

[0103] 3. Degradation Experiment

[0104] The ureteral stent prepared in this embodiment was soaked in artificial urine, and the artificial urine was changed every other week. After 20 days, it was observed that short flocculent degradation products began to appear on a surface of the stent tube, and then the short flocculent degradation products became more and more; until 30 days, only the spiral magnesium wire remained, and then the magnesium wire gradually broke into fragments less than 2 mm from the B end to the A end; and after 40 days, the B end remained only was also degraded into debris.

Embodiment 6: Second Preparation Method of Ureteral Stent with Gradient Degradation (Degradation Time Lasted for 2 to 3 Months)

[0105] 1. Preparation of a Gradient Degradable Magnesium Wire

[0106] A one-meter-long magnesium wire (0.2 mm to 0.4 mm in width, and 0.15 mm in thickness) was complete soaked in a 10% hydrofluoric acid solution, and lifted by 4 cm every 0.5 minute to form a gradient passivation protective film, one end passivated for short time was marked as B end and one end passivated for long time was marked as A end, then washed with acetone after the passivation was ended, and blow-dried for later use.

[0107] 2. Preparation of a Degradable Ureteral Stent

[0108] (1) The gradient degradable magnesium alloy wire (alloying constituent proportions were selected according to Table 8) processed was crimped into a single-strand spiral shape, with a pitch of 2.0 mm to 2.5 mm (as shown in FIG. 1) and a total stent length of 24 cm to 28 cm;

[0109] (2) A degradable medical polyurethane material (polyurethane with PEG200 as an initiator, a copolymer diol of PCL and GA as a soft segment and L-lysine diisocyanate as a hard segment, a number average molecular weight of 120,000 to 150,000 (referring to Solution 5 in Embodiment 10 for specific synthesis method), a breaking strength of 30 MPa, and an elongation at break of 350%) was dissolved in a chloroform solvent to prepare a 8%-15% solution for later use;

[0110] (3) the solution in (2) was repeatedly dip-coated or sprayed on the stent in (1) to manufacture the same into the coated stent (the stent had a tube wall thickness of 0.28 mm); (as shown in FIG. 4 and FIG. 5); and

[0111] (4) the composite material prepared in (3) was dip-coated or sprayed with a hydrophilic coating (such as aqueous solution made of PVA, PVP, and micromolecule hyaluronic acid, etc.), aired, polished and ground into the coated stent.

[0112] 3. Degradation Experiment

[0113] The ureteral stent prepared in this embodiment was soaked in artificial urine, and the artificial urine was changed every other week. After 60 days, it was observed that short flocculent degradation products began to appear on a surface of the stent tube, and then the short flocculent degradation products became more and more; until 70 days, the spiral magnesium wire and trace attachments remained. In the following days, the magnesium wire gradually broke into fragments less than 2 mm from the B end to the A end; and after 90 days, the B end remained only was also degraded into debris.

Embodiment 7: Third Preparation Method of Ureteral Stent with Gradient Degradation (Degradation Time Lasted for 3 to 5 Months)

[0114] 1. Preparation of a Gradient Degradable Magnesium Wire

[0115] A one-meter-long magnesium wire (0.3 mm to 0.4 mm in width, and 0.15 mm in thickness) was completely soaked in a 10% hydrofluoric acid solution, and lifted by 3 cm every 0.4 minute to form a gradient passivation protective film, one end passivated for short time was marked as B end and one end passivated for long time was marked as A end, then washed with acetone after the passivation was ended, and blow-dried for later use.

[0116] 2. Preparation of a Degradable Ureteral Stent

[0117] (1) The gradient degradable magnesium alloy wire (alloying constituent proportions were selected according to Table 8) processed was crimped into a single-strand spiral shape, with a pitch of 2.2 mm to 2.6 mm (as shown in FIG. 1) and a total stent length of 24 cm to 28 cm;

[0118] (2) a degradable medical polyurethane material and PLGA (a weight ratio of 2:1) (polyurethane with PEG400 as an initiator, PCL as a soft segment and L-lysine diisocyanate as a hard segment, a number average molecular weight of 80,000 to 100,000 (referring to Solution 3 in Embodiment 10 for specific synthesis method), a breaking strength of 30 MPa, and an elongation at break of 300%), PLGA (LA:GA=8:2, a viscosity-average molecular weight of 60,000 to 80,000) were dissolved in a chloroform solvent to prepare a 8%-15% solution for later use;

[0119] (3) the solution in (2) was repeatedly dip-coated or sprayed on the stent in step (1) to manufacture the same into the coated stent (the stent had a tube wall thickness of 0.30 mm); (as shown in FIG. 4); and

[0120] (4) the composite material prepared in (3) was dip-coated or sprayed with a hydrophilic coating (such as aqueous solution made of PVA, PVP, and micromolecule hyaluronic acid, etc.), aired, polished and ground into the coated stent.

[0121] 3. Degradation Experiment

[0122] The ureteral stent prepared in this embodiment was soaked in artificial urine, and the artificial urine was changed every other week. After 70 days, it was observed that short flocculent degradation products began to appear on a surface of the stent tube, and then the short flocculent degradation products became more and more; until 90 days, the spiral magnesium wire and trace attachments remained. In the following days, the magnesium wire gradually broke into fragments less than 2 mm from the B end to the A end; and after 120 days, the B end remained only was also degraded into debris.

Embodiment 8: Fourth Preparation Method of Ureteral Stent with Gradient Degradation (Degradation Time Lasted for 20 to 30 Days)

[0123] 1. Preparation of a Gradient Degradable Magnesium Wire

[0124] A one-meter-long magnesium wire (0.2 mm to 0.4 mm in width, and 0.15 mm in thickness) was completely soaked in a 10% hydrofluoric acid solution, and lifted by 3 cm every 0.4 minute to form a gradient passivation protective film, one end passivated for short time was marked as B end and one end passivated for long time was marked as A end, then washed with acetone after the passivation was ended, and blow-dried for later use.

[0125] 2. Preparation of a Degradable Ureteral Stent

[0126] (1) The gradient degradable magnesium alloy wire (alloying constituent proportions were selected according to Table 8) processed was crimped into a single-strand spiral shape, with a pitch of 2.2 mm to 2.6 mm (as shown in FIG. 1) and a total stent length of 28 cm to 32 cm;

[0127] (2) a degradable medical polyurethane material and PLGA (a weight ratio of 5:1) (polyurethane with PEG400 as an initiator, PCL as a soft segment and L-lysine diisocyanate as a hard segment, a number average molecular weight of 50,000 to 70,000 (referring to Solution 1 in Embodiment 10 for specific synthesis method), a breaking strength of 20 MPa, and an elongation at break of 200%), PLGA (LA:GA=6:4, a viscosity-average molecular weight of 40,000 to 60,000) were dissolved in a chloroform solvent and dried into evenly mixed powder, adding the powder into a precise tubule extruder, the magnesium wire in step (1) was spirally fixed in a grinding tool for manufacturing corrugated pipes, the precise tubule extruder was heated to 60° C. to 70° C., the material in step (2) was melt, and extruded into the grinding tool to manufacture the same into a coated stent; and

[0128] (3) the composite material prepared in (2) was dip-coated or sprayed with a hydrophilic coating (such as aqueous solution made of PVA, PVP, and micromolecule hyaluronic acid, etc.), aired, polished and ground into the coated stent with a hydrophily coating.

[0129] 3. Degradation Experiment

[0130] The ureteral stent prepared in this embodiment was soaked in artificial urine, and the artificial urine was changed every other week. From 20 days, it was observed that flocculent degradation products began to appear on a surface of the stent tube, and completely degraded into debris after 30 days.

Embodiment 9: Fourth Preparation Method of Antibacterial Drug-Carrying Ureteral Stent with Gradient Degradation (Degradation Time Lasted for 2 to 3 Months)

[0131] 1. Preparation of a Gradient Degradable Magnesium Wire

[0132] A one-meter-long magnesium wire (0.2 mm to 0.4 mm in width, and 0.13 mm in thickness) was completely soaked in a 10% hydrofluoric acid solution, and lifted by 7 cm every 1 minute to form a gradient passivation protective film, one end passivated for short time was marked as B end and one end passivated for long time was marked as A end, then washed with acetone after the passivation was ended, and blow-dried for later use.

[0133] 2. Preparation of a Degradable Ureteral Stent

[0134] (1) The gradient degradable magnesium alloy wire (alloying constituent proportions were selected according to Table 8) processed was crimped into a single-strand spiral shape, with a pitch of 1.8 mm to 2.2 mm (as shown in FIG. 1) and a total stent length of 26 cm to 28 cm;

[0135] (2) a degradable medical polyurethane material and PLGA (a weight ratio of 2:1) (polyurethane with PEG600 as an initiator, PCL and GA as soft segments and L-lysine diisocyanate as a hard segment, a number average molecular weight of 100,000 to 120,000 (referring to Solution 4 in Embodiment 10 for specific synthesis method), a breaking strength of 20 MPa, and an elongation at break of 300%), PLGA (LA:GA=6:4, a viscosity-average molecular weight of 50,000 to 60,000) were dissolved in a chloroform solvent, and an appropriate amount of antibacterial drugs (which may be one of drugs such as ionic silver, chlorhexidine, antibacterial peptide, quaternary ammonium salt, antibiotics, etc., which could be used in medical appliances) was added into the solution and mixed evenly to prepare a 8-15% solution for later use;

[0136] (3) the solution in (2) was repeatedly dip-coated or sprayed on the stent in (1) to manufacture the same into the coated stent (the stent had a tube wall thickness of 0.3 mm to 0.35 mm); (as shown in FIG. 4); and

[0137] (4) the composite material prepared in (3) was dip-coated or sprayed with a hydrophilic coating (such as aqueous solution made of PVA, PVP, and micromolecule hyaluronic acid, etc.), aired, polished and ground into the coated stent.

Embodiment 10: Synthesis Solutions of Polycaprolactone Polyurethane were as Follows

Solution 1:

[0138] 9.00 g of ε-caprolactone, and 3.00 g of PEG-600 were respectively weighed and added into a test tube with stannous octoate as a catalyst, then a magnetic stirrer was added, vacuumized/filled with nitrogen for three times. Then, an opening of the test tube was sealed under vacuumizing, and the test tube was put into an oil bath pan at 140° C. to react for 24 hours to obtain a linear polymer. Then 2 g of L-lysine diisocyanate and 0.55 g of 1,3-propanediol were weighed, added into the test tube, vacuumized and the opening of the test tube was sealed. The test tube was put into an oil bath pan at 70° C. to react for 4 hours to obtain the final product (a number average molecular weight was tested to be 50,000 to 70,000 by GPC).

Solution 2:

[0139] 9.00 g of ε-caprolactone, and 3.00 g of PEG-200 were respectively weighed and added into a test tube with stannous octoate as a catalyst, then a magnetic stirrer was added, vacuumized/filled with nitrogen for three times. Then, an opening of the test tube was sealed under vacuumizing, and the test tube was put into an oil bath pan at 140° C. to react for 24 hours to obtain a linear polymer. Then 3 g of L-lysine diisocyanate and 0.73 g of 1,3-propanediol were weighed, added into the test tube, vacuumized and the opening of the test tube was sealed. The test tube was put into an oil bath pan at 70° C. to react for 4 hours to obtain the final product (a number average molecular weight was tested to be 60,000 to 80,000 by GPC).

Solution 3:

[0140] 12.00 g of ε-caprolactone, and 3.00 g of PEG-600 were respectively weighed and added into a test tube with stannous octoate as a catalyst, then a magnetic stirrer was added, vacuumized/filled with nitrogen for three times. Then, an opening of the test tube was sealed under vacuumizing, and the test tube was put into an oil bath pan at 140° C. to react for 24 hours to obtain a linear polymer. 3 g of L-lysine diisocyanate and 0.76 g of 1,3-propanediol were weighed, added into the test tube, vacuumized and the opening of the test tube was sealed. The test tube was put into an oil bath pan at 70° C. to react for 4 hours to obtain the final product (a number average molecular weight was tested to be 80,000 to 100,000 by GPC).

Solution 4

[0141] 12.0 g of ε-caprolactone, and 3.0 g of PEG-200 were respectively weighed and added into a vacuum reaction flask with stannous octoate as a catalyst, then a magnetic stirrer was added, vacuumized/filled with nitrogen for three times. Then, an opening of the vacuum reaction flask was sealed under vacuumizing, and the vacuum reaction flask was put into an oil bath pan at 140° C. to react for 24 hours to obtain a linear polymer. 3 g of L-lysine diisocyanate and 0.8 g of 1,3-propanediol were weighed, added into a test tube, vacuumized and an opening of the test tube was sealed. The test tube was put into an oil bath pan at 70° C. to react for 4 hours to obtain the final product (a number average molecular weight was tested to be 100,000 to 120,000 by GPC).

Solution 5

[0142] 12.0 g of ε-caprolactone, and 3.0 g of PEG-600 were respectively weighed and added into a vacuum reaction flask with stannous octoate as a catalyst, then a magnetic stirrer was added, vacuumized/filled with nitrogen for three times. Then, an opening of the vacuum reaction flask was sealed under vacuumizing, and the vacuum reaction flask was put into an oil bath pan at 140° C. to react for 24 hours to obtain a linear polymer. 3 g of L-lysine diisocyanate and 0.7 g of 1,3-propanediol were weighed, added into a test tube, vacuumized and an opening of the test tube was sealed. The test tube was put into an oil bath pan at 70° C. to react for 10 hours to obtain the final product (a number average molecular weight was tested to be 120,000 to 150,000 by GPC).

Solution 6

[0143] 19.0 g of ε-caprolactone, and 3.0 g of PEG-200 were respectively weighed and added into a vacuum reaction flask with stannous octoate as a catalyst, then a magnetic stirrer was added, vacuumized/filled with nitrogen for three times. Then, an opening of the vacuum reaction flask was sealed under vacuumizing, and the vacuum reaction flask was put into an oil bath pan at 140° C. to react for 24 hours to obtain a linear polymer. 3.6 g of L-lysine diisocyanate and 1.56 g of 1,3-propanediol were weighed, added into a test tube, vacuumized and an opening of the test tube was sealed. The test tube was put into an oil bath pan at 70° C. to react for 10 hours to obtain the final product (a number average molecular weight was tested to be 150,000 to 170,000 by GPC).

Solution 7

[0144] 25.0 g of ε-caprolactone, and 3.0 g of PEG-600 were respectively weighed and added into a vacuum reaction flask with stannous octoate as a catalyst, then a magnetic stirrer was added, vacuumized/filled with nitrogen for three times. Then, an opening of the vacuum reaction flask was sealed under vacuumizing, and the vacuum reaction flask was put into an oil bath pan at 140° C. to react for 24 hours to obtain a linear polymer. 4.3 g of L-lysine diisocyanate and 1.88 g of 1,3-propanediol were weighed, added into a test tube, vacuumized and an opening of the test tube was sealed. The test tube was put into an oil bath pan at 70° C. to react for 10 hours to obtain the final product (a number average molecular weight was tested to be 160,000 to 180,000 by GPC).

Solution 8

[0145] 35.0 g of ε-caprolactone, and 5.0 g of PEG-600 were respectively weighed and added into a vacuum reaction flask with stannous octoate as a catalyst, then a magnetic stirrer was added, vacuumized/filled with nitrogen for three times. Then, an opening of the vacuum reaction flask was sealed under vacuumizing, and the vacuum reaction flask was put into an oil bath pan at 140° C. to react for 24 hours to obtain a linear polymer. 5.3 g of L-lysine diisocyanate and 1.7 g of 1,3-propanediol were weighed, added into a test tube, vacuumized and an opening of the test tube was sealed. The test tube was put into an oil bath pan at 70° C. to react for 24 hours to obtain the final product (a number average molecular weight was tested to be 190,000 to 200,000 by GPC).

Solution 9

[0146] 9.0 g of ε-caprolactone, and 3.0 g of PEG-400 were respectively weighed and added into a vacuum reaction flask with stannous octoate as a catalyst, then a magnetic stirrer was added, vacuumized/filled with nitrogen for three times. Then, an opening of the vacuum reaction flask was sealed under vacuumizing, and the vacuum reaction flask was put into an oil bath pan at 140° C. to react for 24 hours to obtain a linear polymer. 3 g of L-lysine diisocyanate and 2.1 g of phenylalanine diamine bound by 1,3-propanediol through an ester bond were weighed, put into a vacuum reaction flask, vacuumized and then an opening of the vacuum reaction flask was sealed, and then the vacuum reaction flask was put into an oil bath pan at 60° C. to react for 4 hours to obtain the final product (a number average molecular weight was tested to be 50,000 to 70,000 by GPC).

Solution 10

[0147] 9.0 g of ε-caprolactone, 2.5 g of GA and 3.0 g of PEG-600 were respectively weighed and added into a vacuum reaction flask with stannous octoate (0.03 wt % % of the total amount) as a catalyst, then a magnetic stirrer was added, vacuumized/filled with nitrogen for three times. Then, an opening of the vacuum reaction flask was sealed under vacuumizing, and the vacuum reaction flask was put into an oil bath pan at 140° C. to react for 24 hours to obtain a linear polymer. 3 g of L-lysine diisocyanate and 2.6 g of indoline diamine bound by 1,3-propanediol through an ester bond were weighed, put into a vacuum reaction flask, vacuumized and then an opening of the vacuum reaction flask was sealed, and then the vacuum reaction flask was put into an oil bath pan at 60° C. to react for 4 hours to obtain the final product (a number average molecular weight was tested to be 60,000 to 80,000 by GPC).

Solution 11

[0148] 12.0 g of ε-caprolactone, 3.0 g of LA, and 3.0 g of PEG-1000 were respectively weighed and added into a vacuum reaction flask with stannous octoate (0.03 wt % % of the total amount) as a catalyst, then a magnetic stirrer was added, vacuumized/filled with nitrogen for three times. Then, an opening of the vacuum reaction flask was sealed under vacuumizing, and the vacuum reaction flask was put into an oil bath pan at 140° C. to react for 24 hours to obtain a linear polymer. 4.3 g of L-lysine diisocyanate and 2.4 g of tryptophan diamine bound by 1,3-propanediol through an ester bond were weighed, put into a vacuum reaction flask, vacuumized and then an opening of the vacuum reaction flask was sealed, and then the vacuum reaction flask was put into an oil bath pan at 55° C. to react for 4 hours to obtain the final product (a number average molecular weight was tested to be 100,000 to 120,000 by GPC).

Solution 12

[0149] 9.0 g of ε-caprolactone, and 3.0 g of PEG-600 were respectively weighed and added into a vacuum reaction flask with stannous octoate (0.03 wt %% of the total amount) as a catalyst, then a magnetic stirrer was added, vacuumized/filled with nitrogen for three times. Then, an opening of the vacuum reaction flask was sealed under vacuumizing, and the vacuum reaction flask was put into an oil bath pan at 140° C. to react for 24 hours to obtain a linear polymer. 3 g of L-lysine diisocyanate and 0.9 g of phenylalanine diamine bound by 1,3-propanediol through an ester bond were weighed, put into a vacuum reaction flask, vacuumized and then an opening of the vacuum reaction flask was sealed, and then the vacuum reaction flask was put into an oil bath pan at 60° C. to react for 4 hours to obtain the final product (a number average molecular weight was tested to be 60,000 to 80,000 by GPC).

Solution 13

[0150] 8.0 g of ε-caprolactone, 6.0 g of PDO, and 4.0 g of PEG-1000 were respectively weighed and added into a vacuum reaction flask with stannous octoate (0.03 wt % % of the total amount) as a catalyst, then a magnetic stirrer was added, vacuumized/filled with nitrogen for three times. Then, an opening of the vacuum reaction flask was sealed under vacuumizing, and the vacuum reaction flask was put into an oil bath pan at 140° C. to react for 24 hours to obtain a linear polymer. 3 g of I-lysine diisocyanate and 0.7 g of 1,3-propanediol were weighed, put into a vacuum reaction flask, vacuumized and then an opening of the vacuum reaction flask was sealed, and then the vacuum reaction flask was put into an oil bath pan at 70° C. to react for 4 hours to obtain the final product (a number average molecular weight was tested to be 50,000 to 70,000 by GPC).

Solution 14

[0151] 12.0 g of ε-caprolactone, and 3.0 g of PEG-400 were respectively weighed and added into a vacuum reaction flask with stannous octoate (0.03 wt %% of the total amount) as a catalyst, then a magnetic stirrer was added, vacuumized/filled with nitrogen for three times. Then, an opening of the vacuum reaction flask was sealed under vacuumizing, and the vacuum reaction flask was put into an oil bath pan at 140° C. to react for 24 hours to obtain a linear polymer. 3 g of L-lysine diisocyanate and 0.55 g of 1,3-propanediol through an ester bond were weighed, put into a vacuum reaction flask, vacuumized and then an opening of the vacuum reaction flask was sealed, and then the vacuum reaction flask was put into an oil bath pan at 80° C. to react for 4 hours to obtain the final product (a number average molecular weight was tested to be 100,000 to 120,000 by GPC).

Solution 15

[0152] 9.00 g of ε-caprolactone, and 3.00 g of PEG-400 were respectively weighed and added into a vacuum reaction flask with stannous octoate (0.03 wt %% of the total amount) as a catalyst, then a magnetic stirrer was added, vacuumized/filled with nitrogen for three times. Then, an opening of the vacuum reaction flask was sealed under vacuumizing, and the vacuum reaction flask was put into an oil bath pan at 140° C. to react for 24 hours to obtain a linear polymer. 3 g of L-lysine diisocyanate and 0.5 g of 1,3-propanediol were weighed, and then added with 0.5 g of PEG-1500, and put into a vacuum reaction flask, vacuumized and then an opening of the vacuum reaction flask was sealed, and then the vacuum reaction flask was put into an oil bath pan at 70° C. to react for 4 hours to obtain the final product (a number average molecular weight was tested to be 80,000 to 100,000 by GPC).

Solution 16

[0153] 8.0 g of ε-caprolactone, and 4.0 g of PEG-200 were respectively weighed and added into a vacuum reaction flask with stannous octoate (0.03 wt %% of the total amount) as a catalyst, then a magnetic stirrer was added, vacuumized/filled with nitrogen for three times. Then, an opening of the vacuum reaction flask was sealed under vacuumizing, and the vacuum reaction flask was put into an oil bath pan at 140° C. to react for 24 hours to obtain a linear polymer. 4 g of L-lysine diisocyanate and 1.8 g of proline diamine bound by 1,3-propanediol through an ester bond were weighed, put into a vacuum reaction flask, vacuumized and then an opening of the vacuum reaction flask was sealed, and then the vacuum reaction flask was put into an oil bath pan at 70° C. to react for 4 hours to obtain the final product (a number average molecular weight was tested to be 100,000 to 120,000 by GPC).

Solution 17

[0154] 6.00 g of ε-caprolactone, and 6.00 g of PEG-400 were respectively weighed and added into a vacuum reaction flask with stannous octoate (0.03 wt %% of the total amount) as a catalyst, then a magnetic stirrer was added, vacuumized/filled with nitrogen for three times. Then, an opening of the vacuum reaction flask was sealed under vacuumizing, and the vacuum reaction flask was put into an oil bath pan at 140° C. to react for 24 hours to obtain a linear polymer. 6 g of L-lysine diisocyanate and 1.1 g of tyrosine diamine bound by 1,3-propanediol through an ester bond were weighed, put into a vacuum reaction flask, vacuumized and then an opening of the vacuum reaction flask was sealed, and then the vacuum reaction flask was put into an oil bath pan at 70° C. to react for 10 hours to obtain the final product (a number average molecular weight was tested to be 120,000 to 150,000 by GPC).

Solution 18

[0155] 8.5 g of ε-caprolactone, and 4.0 g of PEG-300 were respectively weighed and added into a vacuum reaction flask with stannous octoate (0.03 wt %% of the total amount) as a catalyst, then a magnetic stirrer was added, vacuumized/filled with nitrogen for three times. Then, an opening of the vacuum reaction flask was sealed under vacuumizing, and the vacuum reaction flask was put into an oil bath pan at 140° C. to react for 24 hours to obtain a linear polymer. 4 g of L-lysine diisocyanate and 1.8 g of glycine diamine were weighed, put into a vacuum reaction flask, vacuumized and then an opening of the vacuum reaction flask was sealed, and then the vacuum reaction flask was put into an oil bath pan at 70° C. to react for 4 hours to obtain the final product (a number average molecular weight was tested to be 110,000 to 130,000 by GPC).

Embodiment 11: Degradation Experiment of PLGA and PU Ureteral Stent with Gradient Degradation Prepared by the Same Process

[0156] 1. Preparation of a Gradient Degradable Magnesium Wire

[0157] Two one-meter-long magnesium wires (0.25 mm to 0.35 mm in diameter, and 0.12 mm in thickness) were completely soaked in a 15 g/L dipotassium hydrogen phosphate aqueous solution containing 1.2 g/L phytic acid at about 60° C., and lifted by 5 cm every 2.5 minutes to form a gradient passivation protective film, one end passivated for short time was marked as B end and one end passivated for long time was marked as A end.

[0158] 2. Preparation of a PU Degradable Ureteral Stent

[0159] (1) the gradient degradable magnesium alloy wire (alloying constituent proportions were selected according to Table 9) processed was crimped into a single-strand spiral shape, with a pitch of 1.8 mm to 2.5 mm (as shown in FIG. 1) and a a total stent length of 26 cm to 28 cm;

[0160] (2) a degradable medical polyurethane material (polyurethane with PEG400 as an initiator, PCL as a soft segment and L-lysine diisocyanate as a hard segment, a number average molecular weight of 50,000 to 70,000 (referring to Solution 9 in Embodiment 10 for specific synthesis method), a breaking strength of 20 MPa, and an elongation at break of 250%) was dissolved in a chloroform solvent to prepare a 8%-15% solution for later use;

[0161] (3) the solution in step (2) was repeatedly dip-coated or sprayed on the stent in step (1) to manufacture the same into the coated stent (the stent had a tube wall thickness of 0.25 mm to 0.3 mm); and

[0162] (4) the composite material prepared in (3) was dip-coated or sprayed with a hydrophilic coating (such as aqueous solution made of PVA, PVP, and micromolecule hyaluronic acid, etc.), aired, polished and ground into the coated stent.

[0163] 3. Preparation of a PLGA Degradable Ureteral Stent

[0164] (1) the gradient degradable magnesium alloy wire (alloying constituent proportions were selected according to Table 9) processed was crimped into a single-strand spiral shape, with a pitch of 1.8 mm to 2.5 mm (as shown in FIG. 1) and a total stent length of 26 cm to 28 cm;

[0165] (2) the PLGA (LA:GA=7:3) was dissolved in a chloroform solvate to prepare a 8%-15% solution for later use;

[0166] (3) the solution in step (2) was repeatedly dip-coated or sprayed on the stent in step (1) to manufacture the same into the coated stent (the stent had a tube wall thickness of 0.25 mm to 0.3 mm); and

[0167] (4) the composite material prepared in (3) was dip-coated or sprayed with a hydrophilic coating (such as aqueous solution made of PVA, PVP, and micromolecule hyaluronic acid, etc.), aired, polished and ground into the coated stent.

[0168] 4. Preparation of a PU Degradable Ureteral Stent

[0169] (1) a degradable medical polyurethane material (polyurethane with PEG400 as an initiator, PCL as a soft segment and L-lysine diisocyanate as a hard segment, a number average molecular weight of 50,000 to 70,000 (referring to Solution 9 in Embodiment 10 for specific synthesis method), a breaking strength of 20 MPa, and an elongation at break of 250%) was dissolved in a chloroform solvent to prepare a 8%-15% solution for later use; and

[0170] (2) the solution in (1) was repeatedly dip-coated or sprayed on a tetrafluoroethylene tube to manufacture the same into a PU tube (the tube had a wall thickness of 0.25 mm to 0.3 mm).

[0171] 5. Product Performances and Comparative Degradation Experiments

[0172] The two ureteral stents prepared in this embodiment were soaked in artificial urine, and the artificial urine was changed every other week. After 20 days, it was found that flocculent degradation products began to appear on surfaces of the stent tubes, and then the surface degradation products became more and more; until 30 days, only the spiral magnesium wire remained, and then the magnesium wire gradually broke into fragments less than 2 mm from the B end to the A end; and after 40 days, the B end remained only was also degraded into debris.

TABLE-US-00003 Main performances Name of Hand Compressive Tensile Observation of degradation stent feeling resistance strength 20 days 40 days 60 days PU Soft 3.5N  98% Floccules Fine floccules The coated began to dispersed in degradation stent adhere to the products were the surface degradation in the form of solution fine debris PLGA Harder 3.2N  30% Tablets fell A number of The coated off tablets fell off degradation stent products became into large pieces PU tube Soft 0.1N 230% Floccules Broken into The without began to multiple degradation magnesium adhere to segments products were wire the surface small segments and tablets

[0173] The above comparative research results show that: if only PU is used to prepare the stent tube, the compressive resistance is only 0.1 N, the stent tube is broken into multiple segments during the degradation process, and the final degradation fragments are also large, which are not suitable for human implantation. If PLGA is used as the coated stent, the degradation products of the stent are also tablets, which have a potential risk of blocking the ureter. The PU material developed by the disclosure has excellent controllable gradient degradability, which can meet the clinical needs and prepare innovative products meeting clinical use.

Embodiment 12

[0174] The embodiments disclosed in CN105169496A and the embodiments of the disclosure were used to prepare PU by the same process, and influences of the degradation products on the proliferation of mouse fibroblasts in vitro were studied by MTT cell proliferation test. In the evaluation of biomaterial performances, the biocompatibility of the degradation products was a very important index, and usually the simplest and most direct method was to make a basic judgment on an inhibition rate of the degradation products to cells.

[0175] 1. PU synthesis: sample 1: PU1 was synthesized according to the method of Embodiment 1 disclosed in CN105169496A, and PU2 was synthesized according to the method of Solution 1 in Embodiment 10 of the disclosure, molecular weights of which were both 50,000 to 70,000. Due to the substantially close feeding ratios, the main difference was that 1,4-butanediol was used as a chain extender in Embodiment 1 disclosed in CN105169496A, while 1,3-propanediol was used as a chain extender in Solution 1 in Embodiment 10 of the disclosure.

[0176] The specific experiments of PU1 and PU2 were as follows:

[0177] 2. Preparation of degradation products: PU1 and PU2 were respectively purified to make various indexes thereof meet the technical requirements of biomaterials, 2 g of PU1 and 2 g of PU2 were put into a PBS buffer, degraded at 37° C. for 30 days, then the degradation products were filtered, purified with chloroform, cleaned and dried to obtain white powder, and the white powder was extracted with normal saline. The samples obtained were processed as follows:

[0178] (1) sample PU1 (started from 400 ug/ml, twice diluted, and nine concentrations); and

[0179] (2) sample PU2 (started from 400 ug/ml, twice diluted, and nine concentrations).

[0180] 3. Experimental method:

[0181] (1) cells were digested and counted to prepare a cell suspension of 7.5×104 cells/m, and 100 μl of the cell suspension was added to each well of a 96-well cell culture plate;

[0182] (2) the 96-well cell culture plate was placed in a 5% CO2 incubator at 37° C. for 24 hours;

[0183] (3) the drug was diluted with a culture medium to a needed working solution concentration, 100 μl of corresponding drug-containing culture medium was added to each well, and a negative control group was set up a the same time;

[0184] (4) the 96-well cell culture plate was placed in a 5% CO2 incubator at 37° C. for 48 hours;

[0185] (5) the 96-well plate was stained with MTT, wherein λ=490 nm, and OD values were measured;

[0186] 20 μl of MIT (5 mg/ml) was added to each well, and the culture was continued for 4 hours in the incubator;

[0187] a supernatant was discarded, 150 μl of DMSO was added to each well, shaken for 10 minutes and mixed gently,

[0188] λ=490 nm, OD value of each well was read by a microplate reader, and an inhibition rate was calculated; and

[0189] (6) the inhibition rate of each group was calculated.

[00001]$\mathrm{Inhibition}\mathrm{rate}\left(\%\right)=\frac{\begin{array}{c}\mathrm{OD}\mathrm{value}\mathrm{of}\mathrm{negative}\mathrm{control}-\\ \mathrm{OD}\mathrm{value}\mathrm{of}\mathrm{experiment}\mathrm{group}\end{array}}{\mathrm{OD}\mathrm{value}\mathrm{of}\mathrm{experiment}\mathrm{group}}\times 100\%$

[0190] 4. Experiment Results: (Refer to Excel for Details)

TABLE-US-00004 L929 48 h Group Mean ± SD Inhibition rate Negative control 0.629 ± 0.017 PU1  400 ug/ml 0.636 ± 0.016 −25.11%  IC50 >  200 ug/ml 0.631 ± 0.005 −13.32%  400 ug/ml  100 ug/ml 0.635 ± 0.01  −9.95%   50 ug/ml 0.628 ± 0.005 −6.16%   25 ug/ml 0.633 ± 0.014 −5.64% 12.5 ug/ml 0.636 ± 0.005   3.11% 6.25 ug/ml  0.62 ± 0.009   1.43% 3.13 ug/ml 0.633 ± 0.009 −0.64% 1.56 ug/ml 0.626 ± 0.001   0.48% Negative control 0.629 ± 0.017 PU2  800 μM 0.633 ± 0.01  −0.64% IC50 >  400 μM 0.635 ± 0.009 −0.95% 400 ug/ml  200 μM 0.624 ± 0.012   0.79%  100 μM 0.627 ± 0.007   0.32%   50 μM 0.612 ± 0.021   2.70%   25 μM 0.651 ± 0.008 −1.50% 12.5 μM 0.632 ± 0.004 −0.48% 6.25 μM 0.619 ± 0.018   1.59% 3.13 μM 0.634 ± 0.006 −0.79%

[0191] The experiment results show that: the degradation products of the PU obtained by using BDO as the chain extender have certain inhibitory effect on cell growth, showing certain cytotoxicity, while the PU obtained by using 1,3-propanediol has little inhibitory effect on cell growth. The reasons are analyzed as follows: a LD50 value (median lethal dose) of the 1,3-propanediol was 16,080 mg/kg (rats per os); and a LD50 value of the 1,4-butanediol is 1,525 mg/kg (rats per os). In terms of biosecurity, the 1,3-propanediol is one order of magnitude higher than the 1,4-butanediol. The PU of the disclosure uses the 1,3-propanediol instead of the 1,4-butanediol as the chain extender, which is basically free of cytotoxicity, while the cytotoxicity of using the 1, 4-butanediol as the chain extender is secondary. Therefore, through our continuous research on the synthesis of PU materials, the PU of the disclosure has outstanding advantages in the field of implantable medical appliances.

Embodiment 13: Preparation Method of a Drug-Loading Coated Stent for Preventing Postoperative Infection of Intestinal Tract (Degradation Time Lasted for 3 Months to 6 Months)

[0192] (1) A magnesium alloy tube (alloying constituent proportions were selected according to Table 5) was cut into a spiral stent (the stent had an outer diameter of 5 mm which was 9 mm to 10 mm after expansion, and had a length of 3 cm to 5 cm), completely soaked in a 15% hydrofluoric acid solution for 10 minutes to form a passivation protective film, cleaned with acetone after the passivation was ended, and blow-dried for later use;

[0193] (2) a degradable medical polyurethane material (polyurethane with PEG200 as an initiator, PCL and PPDO as soft segments and L-lysine diisocyanate as a hard segment, a number average molecular weight of 160,000 to 180,000 (referring to Solution 7 in Embodiment 10 for specific synthesis method), a breaking strength of 30 MPa, and an elongation at break of 350%) was dissolved in in a chloroform solvent to prepare a 8%-15% solution for later use;

[0194] (3) an appropriate amount of antibiotics was dissolved or suspended in the solution in (2), and dip-coated or evenly sprayed on the stent in (1) to manufacture the same into the coated stent (the stent had a tube wall thickness of 0.4 mm); and

[0195] (4) the coated stent prepared in (3) was dip-coated or sprayed with a hydrophilic coating (such as aqueous solution made of PVA, PVP, and micromolecule hyaluronic acid, etc.), aired, polished and ground into the coated stent.

[0196] In conclusion, through repeated trials and screening, the disclosure screens out nontoxic biomaterials which can meet the requirements of stent preparation, so as to obtain better application in the fields of regenerative medicine and implanted materials.

[0197] The foregoing descriptions are merely embodiments of the disclosure, but are not intended to limit the patent scope of the disclosure. All equivalent structures or equivalent flow transformations made using the description of the disclosure and the accompanying drawings, or being used directly or indirectly in other related technical fields, are similarly included in the protection scope of the disclosure.