Thermo-sensitive bio-absorbable ureteral stent and preparation method of drug sustained-release coating thereof
By designing a thermosensitive bioabsorbable ureteral stent and combining multiple technologies, the problem of mismatch between the degradation rate of the traditional stent matrix and the drug coating was solved, achieving sustained drug release and simultaneous degradation, and improving structural stability and safety.
Patent Information
- Application Number
- CN202511556477.2
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-10-29
- Publication Date
- 2026-01-27
AI Technical Summary
The degradation rates of traditional ureteral stents and drug coatings are difficult to match precisely, leading to drug burst release or residue that causes chronic inflammation. They also have poor structural stability and are prone to breakage or displacement due to ureteral peristalsis or the impact of fluids in the body.
The thermosensitive bioabsorbable ureteral stent is designed with polylactic acid anchoring rings, longitudinal reinforcing lines, transverse responsive lines, and thermosensitive adhesive sheets. By adjusting the PLGA ratio and magnesium ion sustained-release particles, electrostatically assisted microfluidic spraying and photoresponsive crosslinking agents are used to embed enzyme-sensitive short peptide chains and near-infrared light-responsive mesoporous silica nanocarriers, achieving simultaneous drug sustained release and degradation.
It achieves synchronous degradation of the substrate and drug coating, avoids drug burst release or residue, improves structural stability and anti-kink ability, reduces the risk of inflammation and displacement, and ensures timely drug release.
Smart Images
Figure CN121401508A_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the field of ureteral stent technology, and more particularly to a thermosensitive bioabsorbable ureteral stent and a method for preparing a drug-release coating thereof. Background Technology
[0002] Ureteral stents are important implantable devices in the field of urology. Their core function is to temporarily support the ureteral stenosis or injury site, avoid urinary obstruction, provide mechanical support for the ureter after surgery or injury, reduce scar formation, effectively reduce the risk of urine reflux, and prevent hydronephrosis or infection. Currently, these stents mostly use polylactic acid, polycaprolactone and their copolymers as matrix materials, combined with drug-releasing coatings, such as anti-inflammatory and anti-infective drugs, to reduce the risk of postoperative complications.
[0003] Existing ureteral stents are ureteral support structures made of bioabsorbable polymer materials. Combined with a drug-eluting coating, they can be gradually degraded into non-toxic metabolites in the body, eliminating the need for a second surgery to remove them. However, the degradation rates of the traditional stent matrix and the drug-eluting coating are difficult to match precisely. This often results in premature drug release due to premature degradation of the coating, or chronic inflammation caused by coating residue after matrix collapse. Furthermore, the structure has poor stability and is prone to breakage or displacement under ureteral peristalsis or the impact of fluids in the body.
[0004] Therefore, in order to address the problem that the degradation rate of traditional stent substrates and drug coatings is difficult to precisely match, often resulting in premature drug release due to premature degradation of the coating, or chronic inflammation caused by coating residue after substrate collapse, and poor structural stability, which makes them prone to breakage or displacement under ureteral peristalsis or intravenous fluid impact, a thermosensitive bioabsorbable ureteral stent and its drug sustained-release coating preparation method are proposed. Summary of the Invention
[0005] The purpose of this invention is to provide a thermosensitive bioresorbable ureteral stent and a method for preparing its drug-release coating, so as to solve the problems mentioned above, such as the difficulty in accurately matching the degradation rate of the traditional stent substrate and the drug coating, which often leads to drug burst release due to premature degradation of the coating, or the coating residue after substrate collapse causing chronic inflammation, and poor structural stability, which makes it easy to break or displace under the peristalsis of the ureter or the impact of fluid in the body.
[0006] The technical solution of the present invention is: a thermosensitive bioabsorbable ureteral stent and a method for preparing the drug-release coating thereof, comprising polylactic acid anchoring rings, longitudinal reinforcing lines, transverse response lines, threaded guide grooves and thermosensitive adhesive sheets, wherein two polylactic acid anchoring rings are symmetrically arranged vertically, and a longitudinal reinforcing line is arranged circumferentially between the two polylactic acid anchoring rings, and a transverse response line is arranged outside the longitudinal reinforcing line, wherein the longitudinal reinforcing line and the transverse response line constitute a helical stent structure.
[0007] Preferably, the inner sides of the two polylactic acid anchoring rings are provided with threaded guide grooves, and a temperature-sensitive adhesive sheet is provided at the junction of the longitudinal reinforcing diameter and the transverse response diameter, and the temperature-sensitive adhesive sheet is arranged in a ring on the inner side of the longitudinal reinforcing diameter and the transverse response diameter.
[0008] Preferably, the polylactic acid anchoring ring is made of polycaprolactone (PCL) grafted with poly(N-isopropylacrylamide), and the longitudinal reinforcing filaments are oriented fiber bundles formed by melt spinning of polycaprolactone-polyethylene glycol-polylactide (PCL-PEG-PLA) triblock copolymer, with a diameter of 50-200 μm, an orientation degree ≥90%, a tensile modulus of 1.2-1.8 GPa, and a shrinkage rate of 8-12% at body temperature.
[0009] Preferably, the transverse response diameter is a helical wound fiber made from a thermosensitive poly(N-isopropylacrylamide) / polylactic acid-glycolic acid blend through solution spinning, with a radial shrinkage rate of 25-35% at 37°C.
[0010] Preferably, the temperature-sensitive adhesive sheet comprises a temperature-sensitive expansion layer, a bioadhesive layer, and a degradation control layer. The temperature-sensitive expansion layer is made of poloxamer 407 methacrylate / poly(N-vinylcaprolactam) PLX407-MA / PNVCL with a mass ratio of 4:1 to 6:1 and a phase transition temperature of 32 to 34°C. The bioadhesive layer is made of a crosslinker of catechol-modified oxidized hyaluronic acid HA-Cat and iron ions Fe³⁺, with an adhesion strength ≥1.5 N / cm². The degradation control layer is made of a polymalic acid-ε-caprolactone PMA-PCL film covalently modified with uricase, with a thickness of 20 to 50 μm.
[0011] This invention provides another technical solution: a surveying method for a building surveying system, comprising the following steps: S1. By using a biodegradable material made of polylactic acid-glycolic acid copolymer, the degradation rate of the matrix (polylactic acid) and the drug coating is matched. The ratio of lactide to glycolide in the copolymer is adjusted to 3:1, and a magnesium ion sustained-release particle degradation rate regulator is added to ensure that the drug is continuously released during the support period of the stent, avoiding the risk of support failure or residue caused by premature or late degradation of the coating.
[0012] S2. Electrostatic assisted microfluidic spraying technology is used, combined with three-dimensional modeling data of the scaffold surface morphology, to dynamically adjust the spraying parameters and form a drug coating of uniform thickness on complex curved surfaces, eliminating the inconsistency in drug release caused by traditional spraying processes.
[0013] S3. Introduce a photoresponsive crosslinking agent during the coating preparation process. Through ultraviolet gradient irradiation, a dynamic covalent network is formed inside the coating, which enhances the coating's resistance to shrinkage and expansion during phase transition and mechanical expansion, while retaining degradation active sites to maintain degradation synchronicity.
[0014] S4. Embedding a site-specific enzyme-sensitive short peptide chain into the coating allows the coating to undergo rapid degradation triggered by an in vivo enzymatic reaction after drug release, ensuring no polymer residue and adapting to the degradation rate regulation mechanism of step S1.
[0015] S5. Near-infrared light-responsive mesoporous silica nanocarriers with a particle size of 100-300 nm are constructed in the coating. Drugs are loaded inside and encapsulated with degradable enzyme-sensitive hydrogels. When near-infrared light (wavelength 808 nm, power 1-2 W / cm²) is applied externally, the gold nanorods on the surface of the nanocarrier undergo photothermal effect, locally heating to 40-45℃, triggering hydrogel swelling and exposing enzyme-sensitive sites. At the same time, inflammation-related enzymes at the implantation site specifically degrade the hydrogel, achieving dual control of drug release through photothermal initiation and enzyme amplification.
[0016] Compared with the prior art, the beneficial effects of the present invention are: 1. By spirally winding the longitudinal reinforcing diameter and the transverse response diameter, a gradient distribution of mechanical properties is formed. The longitudinal fibers provide axial tensile strength, while the transverse fibers shrink radially by 25-35% at a body temperature of 37°C, dynamically adapting to ureteral peristalsis and improving anti-kinking ability. The polylactic acid anchoring ring has a threaded guide groove on the inner side, combined with a temperature-sensitive adhesive sheet, which reduces the risk of stent displacement through a dual mechanism of physical anchoring and chemical adhesion.
[0017] 2. By adjusting the ratio of lactide / glycolide in PLGA (3:1) and adding magnesium ion slow-release particles, the acidic degradation environment is dynamically neutralized to ensure that the substrate and coating degrade synchronously, avoiding the risk of support failure or inflammation. Combined with 3D modeling and dynamic parameter adjustment, a uniform coating with a thickness deviation of ≤5% is formed on complex morphological surfaces such as threaded guide grooves.
[0018] 3. By embedding enzyme-sensitive short peptide chains in the coating, the coating is rapidly degraded through in vivo enzymatic reactions after drug release, achieving zero residue degradation. In conjunction with near-infrared light (808 nm) triggering the photothermal effect of gold nanorods, the hydrogel microchannels of the mesoporous silica carrier are opened, enabling initial drug release. Furthermore, the enzyme-sensitive short peptide chains in the hydrogel are specifically degraded by inflammation-related enzymes, further regulating the drug release rate to meet the needs of chronic treatment and avoiding the over-release or under-release problems of traditional single triggering mechanisms. This ensures that the degradation rate of the scaffold matrix and the drug coating are matched. Attached Figure Description
[0019] Figure 1The diagram shown is a schematic representation of the overall three-dimensional structure of the present invention; Figure 2 The diagram shown is a three-dimensional structural schematic of the threaded guide groove of the present invention. Figure 3 The diagram shown is a three-dimensional structural schematic of the temperature-sensitive adhesive sheet of the present invention. Figure 4 The diagram shown is a schematic flowchart of the drug sustained-release coating preparation method of the present invention.
[0020] Explanation of reference numerals in the attached diagram: 1. Polylactic acid anchoring ring; 2. Longitudinal reinforcing radii; 3. Transverse response radii; 4. Threaded guide groove; 5. Temperature-sensitive adhesive sheet. Detailed Implementation
[0021] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.
[0022] Please see Figures 1-4 This invention provides an embodiment of a thermosensitive bioabsorbable ureteral stent and a method for preparing its drug-release coating, comprising a polylactic acid anchoring ring 1, a longitudinal reinforcing line 2, a transverse response line 3, a threaded guide groove 4, and a thermosensitive adhesive sheet 5. Two polylactic acid anchoring rings 1 are symmetrically arranged vertically, and a longitudinal reinforcing line 2 is arranged circumferentially between the two polylactic acid anchoring rings 1. A transverse response line 3 is arranged outside the longitudinal reinforcing line 2, and the longitudinal reinforcing line 2 and the transverse response line 3 constitute a helical stent structure.
[0023] The inner sides of the two polylactic acid anchoring rings 1 are provided with threaded guide grooves 4, and a temperature-sensitive adhesive sheet 5 is provided at the junction of the longitudinal reinforcing line 2 and the transverse response line 3. The temperature-sensitive adhesive sheet 5 is arranged in a ring on the inner side of the longitudinal reinforcing line 2 and the transverse response line 3.
[0024] The polylactic acid anchoring ring 1 is made of polycaprolactone (PCL) grafted with poly(N-isopropylacrylamide), and the longitudinal reinforcing wire 2 is a directional fiber bundle made by melt spinning of polycaprolactone-polyethylene glycol-polylactide (PCL-PEG-PLA) triblock copolymer, with a diameter of 50-200 μm, an orientation degree ≥90%, a tensile modulus of 1.2-1.8 GPa, and a shrinkage rate of 8-12% at body temperature.
[0025] The transverse response diameter 3 is a spirally wound fiber made from a thermosensitive poly(N-isopropylacrylamide) / polylactic acid-glycolic acid blend through solution spinning, with a radial shrinkage rate of 25-35% at 37°C.
[0026] The thermosensitive adhesive sheet 5 comprises a thermosensitive expansion layer, a bioadhesive layer, and a degradation control layer. The thermosensitive expansion layer is made of poloxamer 407 methacrylate / poly(N-vinylcaprolactam) PLX407-MA / PNVCL with a mass ratio of 4:1 to 6:1 and a phase transition temperature of 32 to 34°C. The bioadhesive layer is made of a crosslinking product of catechol-modified oxidized hyaluronic acid HA-Cat and iron ions Fe³⁺, with an adhesion strength ≥1.5 N / cm². The degradation control layer is made of a polymalic acid-ε-caprolactone PMA-PCL film covalently modified with uricase, with a thickness of 20 to 50 μm.
[0027] To better demonstrate the preparation method of the thermosensitive bioabsorbable ureteral stent and its drug-release coating, this embodiment describes the preparation method of the thermosensitive bioabsorbable ureteral stent and its drug-release coating, which includes the following steps: S1. By using a biodegradable material made of polylactic acid-glycolic acid copolymer, the degradation rate of the matrix (polylactic acid) and the drug coating is matched. The ratio of lactide to glycolide in the copolymer is adjusted to 3:1, and a magnesium ion sustained-release particle degradation rate regulator is added to ensure that the drug is continuously released during the support period of the stent, avoiding the risk of support failure or residue caused by premature or late degradation of the coating.
[0028] S2. Electrostatic assisted microfluidic spraying technology is used, combined with three-dimensional modeling data of the scaffold surface morphology, to dynamically adjust the spraying parameters and form a drug coating of uniform thickness on complex curved surfaces, eliminating the inconsistency in drug release caused by traditional spraying processes.
[0029] S3. Introduce a photoresponsive crosslinking agent during the coating preparation process. Through ultraviolet gradient irradiation, a dynamic covalent network is formed inside the coating, which enhances the coating's resistance to shrinkage and expansion during phase transition and mechanical expansion, while retaining degradation active sites to maintain degradation synchronicity.
[0030] S4. Embedding a site-specific enzyme-sensitive short peptide chain into the coating allows the coating to undergo rapid degradation triggered by an in vivo enzymatic reaction after drug release, ensuring no polymer residue and adapting to the degradation rate regulation mechanism of step S1.
[0031] S5. Near-infrared light-responsive mesoporous silica nanocarriers with a particle size of 100-300 nm are constructed in the coating. Drugs are loaded inside and encapsulated with degradable enzyme-sensitive hydrogels. When near-infrared light (wavelength 808 nm, power 1-2 W / cm²) is applied externally, the gold nanorods on the surface of the nanocarrier undergo photothermal effect, locally heating to 40-45℃, triggering hydrogel swelling and exposing enzyme-sensitive sites. At the same time, inflammation-related enzymes at the implantation site specifically degrade the hydrogel, achieving dual control of drug release through photothermal initiation and enzyme amplification.
[0032] The following describes the working process of the system in two different scenarios.
[0033] like Figures 1-4 As shown, Example 1: Preparation of a thermosensitive bioresorbable ureteral stent First, the longitudinal reinforcing diameter 2 is composed of triblock copolymer oriented fiber bundles with high orientation and tensile modulus, providing longitudinal support strength for the stent and maintaining ureteral lumen patency. It can shrink by 8-12% under body temperature, which may assist in stent fixation through contraction force. The transverse response diameter 3 is made of thermosensitive blended fibers spirally wound, which shrinks radially by 25-35% at 37°C. This characteristic allows the stent to tighten radially under body temperature, closely adhering to the inner wall of the ureter, enhancing stability, and avoiding tissue damage caused by excessive expansion. The polylactic acid anchoring ring 1 is made of polycaprolactone (PCL) grafted with poly(N-isopropylacrylamide) and injection molded into a ring structure by melt blending.
[0034] Next, the longitudinal reinforcing diameter 2 is wound in a loop between the two polylactic acid anchoring rings 1 to form a helical skeleton. A thermosensitive adhesive sheet 5 is coated at the junction of the longitudinal reinforcing diameter 2 and the transverse response diameter 3 and cured at 37°C for 30 minutes. After entering the body, the temperature rises to 37°C, the material gels and expands, filling the tiny gaps between the stent and the ureteral wall to form a physical anchor.
[0035] Finally, the scaffold matrix is completely degraded within 12 months, while the coating degradation cycle is 11-13 months. Through magnesium ion slow-release regulation, the synchronization error with the matrix is <8%. The efficiency of uricase in the degradation regulation layer in neutralizing acidic products reaches 85%, reducing the risk of inflammation.
[0036] like Figures 1-4 As shown in Example 2: Verification of Drug Release and Controlled Release Effect First, mesoporous silica nanoparticles were used, with gold nanorods modified on the surface and levofloxacin hydrochloride loaded inside, to encapsulate the drug in a gelatin-methacrylamide hydrogel containing short peptide chains of MMP-2 substrate.
[0037] Then, the hydrogel was irradiated with near-infrared light for 5 minutes and locally heated to 42°C. The hydrogel swelled and released the initial dose. In a simulated inflammatory environment, the short peptide chains were cleaved by enzymes to accelerate the degradation of the hydrogel.
[0038] Finally, CT scans showed that the stent degraded uniformly within 12 months without structural collapse, and tissue sections showed no chronic inflammation in the degradation area and good regeneration of surrounding tissue.
[0039] The above is the entire working process of the device, and all contents not described in detail in this specification are existing technologies known to those skilled in the art.
[0040] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.
Claims
1. A thermosensitive bioabsorbable ureteral stent, comprising a polylactic acid anchoring ring (1); characterized in that: It also includes a longitudinal reinforcing line (2), a transverse response line (3), a threaded guide groove (4) and a temperature-sensitive adhesive sheet (5). Two polylactic acid anchoring rings (1) are symmetrically arranged vertically. A longitudinal reinforcing line (2) is arranged in a ring between the two polylactic acid anchoring rings (1). A transverse response line (3) is arranged outside the longitudinal reinforcing line (2). The longitudinal reinforcing line (2) and the transverse response line (3) constitute a spiral support structure.
2. The thermosensitive bioabsorbable ureteral stent according to claim 1, characterized in that: The inner sides of the two polylactic acid anchoring rings (1) are provided with threaded guide grooves (4), and a temperature-sensitive adhesive sheet (5) is provided at the junction of the longitudinal reinforcing line (2) and the transverse response line (3). The temperature-sensitive adhesive sheet (5) is arranged in a ring on the inner side of the longitudinal reinforcing line (2) and the transverse response line (3).
3. The thermosensitive bioabsorbable ureteral stent according to claim 1, characterized in that: The polylactic acid anchoring ring (1) is made of polycaprolactone (PCL) grafted with poly(N-isopropylacrylamide), and the longitudinal reinforcing wire (2) is a directional fiber bundle made by melt spinning of polycaprolactone-polyethylene glycol-polylactide (PCL)-PEG-PLA triblock copolymer, with a diameter of 50-200 μm, an orientation degree of ≥90%, a tensile modulus of 1.2-1.8 GPa, and a shrinkage rate of 8-12% at body temperature.
4. The thermosensitive bioabsorbable ureteral stent according to claim 1, characterized in that: The transverse response diameter (3) is a spiral wound fiber made by solution spinning of thermosensitive poly(N-isopropylacrylamide) / polylactic acid-glycolic acid blend, with a radial shrinkage rate of 25-35% at 37°C.
5. The thermosensitive bioabsorbable ureteral stent according to claim 1, characterized in that: The thermosensitive adhesive sheet (5) includes a thermosensitive expansion layer, a bioadhesive layer, and a degradation control layer. The thermosensitive expansion layer is made of poloxamer 407 methacrylate / poly(N-vinylcaprolactam) PLX407-MA / PNVCL with a mass ratio of 4:1 to 6:1 and a phase transition temperature of 32 to 34°C. The bioadhesive layer is made of catechol-modified oxidized hyaluronic acid HA-Cat and iron ion Fe³⁺ coordination crosslinker with an adhesion strength ≥1.5 N / cm². The degradation control layer is made of polymalic acid-ε-caprolactone PMA-PCL film covalently modified with uricase with a thickness of 20 to 50 μm.
6. The method for preparing the drug-release coating of the thermosensitive bioabsorbable ureteral stent according to claim 1, characterized in that: Includes the following steps: S1. By using a biodegradable material made of polylactic acid-glycolic acid copolymer, the degradation rate of the matrix (polylactic acid) and the drug coating is matched. The ratio of lactide to glycolide in the copolymer is adjusted to 3:1, and a magnesium ion sustained-release particle degradation rate regulator is added to ensure that the drug is continuously released during the support period of the stent, avoiding the risk of support failure or residue caused by premature or late degradation of the coating. S2. Electrostatic assisted microfluidic spraying technology is adopted, combined with three-dimensional modeling data of the scaffold surface morphology, and spraying parameters are dynamically adjusted to form a drug coating with uniform thickness on complex curved surfaces, eliminating the inconsistency in drug release caused by traditional spraying processes. S3. Introduce a photoresponsive crosslinking agent during the coating preparation process. Through ultraviolet gradient irradiation, a dynamic covalent network is formed inside the coating, which enhances the coating's resistance to shrinkage and expansion during phase change and mechanical expansion, while retaining degradation active sites to maintain degradation synchronicity. S4. Embedding a site-specific enzyme-sensitive short peptide chain into the coating allows the coating to be rapidly degraded in vivo after drug release, ensuring no polymer residue and adapting to the degradation rate regulation mechanism of step S1. S5. Near-infrared light-responsive mesoporous silica nanocarriers with a particle size of 100-300 nm are constructed in the coating. Drugs are loaded inside and encapsulated with degradable enzyme-sensitive hydrogels. When near-infrared light (wavelength 808 nm, power 1-2 W / cm²) is applied externally, the gold nanorods on the surface of the nanocarrier undergo photothermal effect, locally heating to 40-45℃, triggering hydrogel swelling and exposing enzyme-sensitive sites. At the same time, inflammation-related enzymes at the implantation site specifically degrade the hydrogel, achieving dual control of drug release through photothermal initiation and enzyme amplification.