An airway stent coating composition for treating benign airway stenosis and a method of making the same
Patent Information
- Application Number
- CN202611348875.X
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2026-09-02
- Publication Date
- 2026-10-16
AI Technical Summary
本发明提供了一种治疗良性气道狭窄的气道支架涂覆组合物及其制备方法,改性甘草酸具有抗炎、抑制纤维化等作用,可减轻气道局部炎症反应,减少瘢痕组织形成;改性PLGA微球负载的吡非尼酮能进一步抑制成纤维细胞增殖和胶原沉积,协同作用,从多个靶点共同抑制气道狭窄的病理进程,显著降低气管狭窄度。本发明改性PLGA微球采用聚乳酸-羟基乙酸共聚物作为载体,其生物降解性良好,在体内可逐步降解为无害产物并排出,避免了长期留置带来的异物反应;聚赖氨酸修饰进一步提高了微球的生物相容性,降低了支架对气道黏膜的刺激。改性甘草酸由天然甘草酸单铵盐经温和工艺改性而成,保留了其生物活性的同时,降低了潜在毒性,与机体的相容性更佳,减少了不良反应的发生风险。本发明组合物中的改性甘草酸和聚赖氨酸均具有一定的抑菌活性,二者结合可有效抑制金黄色葡萄球菌等常见致病菌的生长繁殖。本发明采用APTES对硅酮支架进行表面修饰,通过真空紫外灯辐照活化支架表面,使APTES与支架表面形成稳定结合,为后续改性甘草酸和改性PLGA微球的固定提供了可靠位点,确保涂覆层在气道内复杂环境中不易脱落。改性PLGA微球的结构设计可实现吡非尼酮的缓慢释放,延长药物作用时间,使治疗效果更持久,减少了频繁干预的需求。
Smart Images

Figure CN122912192A_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the field of airway stent coating technology, specifically to an airway stent coating composition for treating benign airway stenosis and its preparation method. Background Technology
[0002] Airway stenosis is a congenital condition or caused by diseases such as infection, airway tumors, trauma, and endobronchial tuberculosis. Clinical manifestations include cough, sputum production, dyspnea, and even respiratory failure, which can be life-threatening. Tracheal stents are an interventional treatment for various benign or malignant airway stenosis, relieving patients' tracheal obstruction symptoms and providing temporary tracheal dilation or support. Summary of the Invention
[0003] To address the shortcomings of existing technologies, this invention proposes an airway stent coating composition for treating benign airway stenosis and its preparation method.
[0004] This invention is achieved through the following technical solution: An airway stent coating composition for treating benign airway stenosis, the raw materials for which are prepared include the following components in parts by weight: 8-12 parts modified glycyrrhizic acid, 6-9 parts modified PLGA microspheres, and 2-3 parts γ-aminopropyltriethoxysilane (APTES).
[0005] Furthermore, the raw materials for preparing glycyrrhizic acid include the following components in parts by weight: 2-3 parts of glycyrrhizic acid monoammonium salt and 1-1.5 parts of sodium periodate (NaIO4).
[0006] Furthermore, the method for preparing glycyrrhizic acid includes the following steps: L1. Dissolve NaIO4 in ultrapure water to prepare a 0.1 g / mL NaIO4 aqueous solution. Add glycyrrhizic acid monoammonium salt to ultrapure water and stir at 60℃ and 300 rpm to dissolve. Add the NaIO4 aqueous solution dropwise under the protection of light. L2. After the addition of step L1 is completed, the mixture is stirred for 4 h, ethylene glycol is added, and stirring is continued for 30 min. The mixture is then dialyzed in ultrapure water at 50℃ for 48 h and freeze-dried to obtain modified glycyrrhizic acid.
[0007] Furthermore, in step L1, the mass concentration of the glycyrrhizic acid monoammonium salt in ultrapure water is 50 mg / mL.
[0008] Furthermore, in step L1, the volume ratio of ethylene glycol to ultrapure water is 1:25.
[0009] Furthermore, the raw materials for preparing the modified @PLGA microspheres include the following components in parts by weight: 2-3 parts pirfenidone, 6-9 parts polylactic acid-glycolic acid copolymer (PLGA), and 5-8 parts polylysine.
[0010] Furthermore, the preparation method of the PFD@PLGA microspheres includes the following steps: V1. Dissolve pirfenidone and PLGA in dichloromethane (DCM) to obtain a PFD / PLGA mixture. Prepare a 0.4% w / v PVA aqueous solution. Add the PFD / PLGA mixture dropwise to the PVA solution. Homogenize at 5000 rpm for 5 min in an ice-water bath and stir at 500-600 rpm to evaporate the organic solvent. V2. After stirring in step V1, centrifuge at 8000 rpm for 10 min, wash the precipitate with deionized water, vacuum dry, disperse it in 0.1 M NaOH solution at a material-to-liquid ratio of 1 g: 50 mL, stir at room temperature for 10 min, filter, wash with distilled water, soak in 2 mg / mL polylysine aqueous solution for 10-12 h, filter under vacuum, wash the filter cake with distilled water, vacuum dry to obtain lysine PLGA microspheres.
[0011] Furthermore, in step V1, the mass-volume fraction of the PLGA in the DCM is 5% w / v.
[0012] Furthermore, in step V1, the mass ratio of PLGA to PVA is 4:5.
[0013] Furthermore, the present invention also provides a method for preparing the airway stent coating composition for treating benign airway stenosis, comprising the following steps: S1. Mix deionized water and ethanol, add γ-aminopropyltriethoxysilane (APTES), stir magnetically for 1 h to obtain APTES solution, soak the silicone scaffold in anhydrous ethanol for 2 h, dry it with nitrogen, irradiate it under a vacuum ultraviolet lamp (photon energy 7.2 eV) for 200 s, immediately put it into the APTES solution, heat at 90 °C for 1 h, wash with ethanol, dry it with nitrogen, and react it in an oven at 110 °C for 5 min. S2. Prepare an NHS / EDCI solution by adding NHS and EDCI to deionized water. Dissolve modified glycyrrhizic acid in DMF solvent at a ratio of 10 mg / mL. Add the NHS / EDCI solution dropwise and stir for 2 h. Adjust the pH to 5 during the process. Add the silicone scaffold treated in step S1 and react for 12 h. Wash with deionized water and dry under vacuum. S3. Add the modified PLGA microspheres to deionized water, add the silicone stent treated in step S2, react for 12 hours, rinse the surface with deionized water, and dry to obtain the airway stent coating composition for treating benign airway stenosis.
[0014] Further, in step S1, the surface area of the silicone scaffold to the volume ratio of the APTES solution is 1 cm².2 1mL.
[0015] Further, in step S1, the volume ratio of deionized water, ethanol and APTES is 1:18:1.
[0016] Further, in step S2, the mass concentration of NHS in the NHS / EDCI solution in deionized water is 10 mg / mL.
[0017] Further, in step S2, the mass ratio of the modified glycyrrhizic acid, NHS and EDCI is 1:0.5:0.8.
[0018] Further, in step S3, the mass concentration of the modified PLGA in deionized water is 10 mg / mL.
[0019] Furthermore, the ratio of modified glycyrrhizic acid to APTES is 1 g: 1.5 mL.
[0020] Compared with the prior art, the present invention has the following beneficial effects: This invention provides an airway stent coating composition for treating benign airway stenosis and its preparation method. Modified glycyrrhizic acid possesses anti-inflammatory and anti-fibrotic effects, reducing local airway inflammation and scar tissue formation. Pirfenidone loaded onto modified PLGA microspheres further inhibits fibroblast proliferation and collagen deposition, synergistically inhibiting the pathological progression of airway stenosis from multiple targets and significantly reducing tracheal stenosis. The modified PLGA microspheres of this invention use polylactic acid-glycolic acid copolymer as a carrier, which has good biodegradability and can be gradually degraded into harmless products and excreted in vivo, avoiding foreign body reactions caused by long-term placement. Polylysine modification further improves the biocompatibility of the microspheres and reduces the irritation of the stent to the airway mucosa. The modified glycyrrhizic acid is prepared from natural glycyrrhizic acid monoammonium salt through a mild modification process, retaining its biological activity while reducing potential toxicity, improving compatibility with the body, and reducing the risk of adverse reactions. The modified glycyrrhizic acid and polylysine in the composition of this invention both possess certain antibacterial activities. Their combination can effectively inhibit the growth and reproduction of common pathogenic bacteria such as Staphylococcus aureus. This invention uses APTES to modify the surface of a silicone scaffold. The scaffold surface is activated by vacuum ultraviolet irradiation, allowing APTES to form a stable bond with the scaffold surface. This provides reliable sites for the subsequent fixation of modified glycyrrhizic acid and modified PLGA microspheres, ensuring that the coating layer is not easily detached in the complex environment of the airway. The structural design of the modified PLGA microspheres enables the slow release of pirfenidone, prolonging the drug's action time, resulting in a more durable therapeutic effect and reducing the need for frequent interventions. Attached Figure Description
[0021] To more clearly illustrate the technical solutions in this invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only for this invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.
[0022] Figure 1 The therapeutic effects of silicone stents obtained in Examples 1-3 and Comparative Examples 1-2 of this invention on airway stenosis; Figure 2 The antibacterial effect of the silicone scaffolds obtained in Examples 1-3 and Comparative Examples 1-2 of this invention is shown. Detailed Implementation
[0023] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to specific embodiments. However, this invention is not limited to the following embodiments. It should be noted that, unless otherwise specified, all chemical reagents involved in this invention are purchased through commercial channels.
[0024] Example 1: An airway stent coating composition for treating benign airway stenosis, the raw materials for preparation include the following components in parts by weight: 12 parts modified glycyrrhizic acid, 9 parts modified PLGA microspheres, and 3 parts γ-aminopropyltriethoxysilane (APTES).
[0025] The raw materials for preparing glycyrrhizic acid include the following components in parts by weight: 3 parts of glycyrrhizic acid monoammonium salt and 1.5 parts of sodium periodate (NaIO4).
[0026] The preparation method of glycyrrhizic acid includes the following steps: L1. Dissolve NaIO4 in ultrapure water to prepare a 0.1 g / mL NaIO4 aqueous solution. Add glycyrrhizic acid monoammonium salt to ultrapure water and stir at 60℃ and 300 rpm to dissolve. Add the NaIO4 aqueous solution dropwise under the protection of light. The mass concentration of glycyrrhizic acid monoammonium salt in ultrapure water is 50 mg / mL, and the volume ratio of ethylene glycol to ultrapure water is 1:25. L2. After the addition of step L1 is completed, the mixture is stirred for 4 h, ethylene glycol is added, and stirring is continued for 30 min. The mixture is then dialyzed in ultrapure water at 50℃ for 48 h and freeze-dried to obtain modified glycyrrhizic acid.
[0027] The raw materials for preparing modified PLGA microspheres include the following components in parts by weight: 3 parts pirfenidone, 9 parts polylactic acid-glycolic acid copolymer (PLGA), and 8 parts polylysine.
[0028] The preparation method of modified PLGA microspheres includes the following steps: V1. Pirfenidone and PLGA were dissolved in dichloromethane (DCM) to obtain a PFD / PLGA mixture. PVA was prepared into a 0.4% w / v PVA aqueous solution. The PFD / PLGA mixture was added dropwise to the PVA solution. The mixture was homogenized at 5000 rpm for 5 min in an ice-water bath and stirred at 600 rpm to evaporate the organic solvent. The mass volume fraction of PLGA in DCM was 5% w / v, and the mass ratio of PLGA to PVA was 4:5. V2. After stirring in step V1, centrifuge at 8000 rpm for 10 min, wash the precipitate with deionized water, vacuum dry, disperse it in 0.1 M NaOH solution at a material-to-liquid ratio of 1 g: 50 mL, stir at room temperature for 10 min, filter, wash with distilled water, soak in 2 mg / mL polylysine aqueous solution for 12 h, filter under vacuum, wash the filter cake with distilled water, vacuum dry, and obtain lysine PLGA microspheres.
[0029] This embodiment also provides a method for preparing the airway stent coating composition for treating benign airway stenosis, comprising the following steps: S1. Mix deionized water and ethanol, add γ-aminopropyltriethoxysilane (APTES), and stir magnetically for 1 h to obtain an APTES solution. Immerse the silicone scaffold in anhydrous ethanol for 2 h, dry it under nitrogen, irradiate it under a vacuum UV lamp (photon energy 7.2 eV) for 200 s, immediately immerse it in the APTES solution, heat at 90 °C for 1 h, wash with ethanol, dry it under nitrogen, and react it in an oven at 110 °C for 5 min. The surface area ratio of the silicone scaffold to the volume ratio of the APTES solution is 1 cm³. 2 1 mL; the volume ratio of deionized water, ethanol and APTES is 1:18:1; S2. Prepare an NHS / EDCI solution by adding NHS and EDCI to deionized water. Dissolve modified glycyrrhizic acid in DMF solvent at a ratio of 10 mg / mL. Add the NHS / EDCI solution dropwise and stir for 2 h, adjusting the pH to 5 during the process. Add the silicone scaffold treated in step S1 and react for 12 h. Wash with deionized water and vacuum dry. The mass concentration of NHS in the NHS / EDCI solution in deionized water is 10 mg / mL. The mass ratio of modified glycyrrhizic acid, NHS, and EDCI is 1:0.5:0.8. S3. Add modified PLGA microspheres to deionized water, add the silicone stent treated in step S2, react for 12 h, rinse the surface with deionized water, and dry to obtain an airway stent coating composition for treating benign airway stenosis; the mass concentration of modified PLGA in deionized water is 10 mg / mL; the ratio of glycyrrhizic acid to APTES is 1 g:1.5 mL.
[0030] Example 2: An airway stent coating composition for treating benign airway stenosis, the raw materials for preparation include the following components in parts by weight: 8 parts modified glycyrrhizic acid, 6 parts modified PLGA microspheres, and 2 parts γ-aminopropyltriethoxysilane (APTES).
[0031] The raw materials for preparing glycyrrhizic acid include the following components in parts by weight: 2 parts of glycyrrhizic acid monoammonium salt and 1 part of sodium periodate (NaIO4).
[0032] The preparation method of glycyrrhizic acid includes the following steps: L1. Dissolve NaIO4 in ultrapure water to prepare a 0.1 g / mL NaIO4 aqueous solution. Add glycyrrhizic acid monoammonium salt to ultrapure water and stir at 60℃ and 300 rpm to dissolve. Add the NaIO4 aqueous solution dropwise under the protection of light. The mass concentration of glycyrrhizic acid monoammonium salt in ultrapure water is 50 mg / mL, and the volume ratio of ethylene glycol to ultrapure water is 1:25. L2. After the addition of step L1 is completed, the mixture is stirred for 4 h, ethylene glycol is added, and stirring is continued for 30 min. The mixture is then dialyzed in ultrapure water at 50℃ for 48 h and freeze-dried to obtain modified glycyrrhizic acid.
[0033] The raw materials for preparing modified PLGA microspheres include the following components in parts by weight: 2 parts pirfenidone, 6 parts polylactic acid-glycolic acid copolymer (PLGA), and 5 parts polylysine.
[0034] The preparation method of modified PLGA microspheres includes the following steps: V1. Pirfenidone and PLGA were dissolved in dichloromethane (DCM) to obtain a PFD / PLGA mixture. PVA was prepared into a 0.4% w / v PVA aqueous solution. The PFD / PLGA mixture was added dropwise to the PVA solution. The mixture was homogenized at 5000 rpm for 5 min in an ice-water bath and stirred at 500 rpm to evaporate the organic solvent. The mass volume fraction of PLGA in DCM was 5% w / v, and the mass ratio of PLGA to PVA was 4:5. V2. After stirring in step V1, centrifuge at 8000 rpm for 10 min, wash the precipitate with deionized water, vacuum dry, disperse it in 0.1 M NaOH solution at a material-to-liquid ratio of 1 g: 50 mL, stir at room temperature for 10 min, filter, wash with distilled water, soak in 2 mg / mL polylysine aqueous solution for 10 h, filter, wash the filter cake with distilled water, vacuum dry to obtain lysine PLGA microspheres.
[0035] This embodiment also provides a method for preparing the airway stent coating composition for treating benign airway stenosis, comprising the following steps: S1. Mix deionized water and ethanol, add γ-aminopropyltriethoxysilane (APTES), and stir magnetically for 1 h to obtain an APTES solution. Immerse the silicone scaffold in anhydrous ethanol for 2 h, dry it under nitrogen, irradiate it under a vacuum UV lamp (photon energy 7.2 eV) for 200 s, immediately immerse it in the APTES solution, heat at 90 °C for 1 h, wash with ethanol, dry it under nitrogen, and react it in an oven at 110 °C for 5 min. The surface area ratio of the silicone scaffold to the volume ratio of the APTES solution is 1 cm³. 2 1 mL; the volume ratio of deionized water, ethanol and APTES is 1:18:1; S2. Prepare an NHS / EDCI solution by adding NHS and EDCI to deionized water. Dissolve modified glycyrrhizic acid in DMF solvent at a ratio of 10 mg / mL. Add the NHS / EDCI solution dropwise and stir for 2 h, adjusting the pH to 5 during the process. Add the silicone scaffold treated in step S1 and react for 12 h. Wash with deionized water and vacuum dry. The mass concentration of NHS in the NHS / EDCI solution in deionized water is 10 mg / mL. The mass ratio of modified glycyrrhizic acid, NHS, and EDCI is 1:0.5:0.8. S3. Add modified PLGA microspheres to deionized water, add the silicone stent treated in step S2, react for 12 h, rinse the surface with deionized water, and dry to obtain an airway stent coating composition for treating benign airway stenosis; the mass concentration of modified PLGA in deionized water is 10 mg / mL; the ratio of glycyrrhizic acid to APTES is 1 g:1.5 mL.
[0036] Example 3: An airway stent coating composition for treating benign airway stenosis, the raw materials for preparation include the following components in parts by weight: 10 parts modified glycyrrhizic acid, 8 parts modified PLGA microspheres, and 2.5 parts γ-aminopropyltriethoxysilane (APTES).
[0037] The raw materials for preparing glycyrrhizic acid include the following components in parts by weight: 2.5 parts of monoammonium glycyrrhizate and 1.2 parts of sodium periodate (NaIO4).
[0038] The preparation method of glycyrrhizic acid includes the following steps: L1. Dissolve NaIO4 in ultrapure water to prepare a 0.1 g / mL NaIO4 aqueous solution. Add glycyrrhizic acid monoammonium salt to ultrapure water and stir at 60℃ and 300 rpm to dissolve. Add the NaIO4 aqueous solution dropwise under the protection of light. The mass concentration of glycyrrhizic acid monoammonium salt in ultrapure water is 50 mg / mL, and the volume ratio of ethylene glycol to ultrapure water is 1:25. L2. After the addition of step L1 is completed, the mixture is stirred for 4 h, ethylene glycol is added, and stirring is continued for 30 min. The mixture is then dialyzed in ultrapure water at 50℃ for 48 h and freeze-dried to obtain modified glycyrrhizic acid.
[0039] The raw materials for preparing modified PLGA microspheres include the following components in parts by weight: 2.5 parts pirfenidone, 8 parts polylactic acid-glycolic acid copolymer (PLGA), and 6 parts polylysine.
[0040] The preparation method of modified PLGA microspheres includes the following steps: V1. Pirfenidone and PLGA were dissolved in dichloromethane (DCM) to obtain a PFD / PLGA mixture. PVA was prepared into a 0.4% w / v PVA aqueous solution. The PFD / PLGA mixture was added dropwise to the PVA solution. The mixture was homogenized at 5000 rpm for 5 min in an ice-water bath and stirred at 550 rpm to evaporate the organic solvent. The mass volume fraction of PLGA in DCM was 5% w / v, and the mass ratio of PLGA to PVA was 4:5. V2. After stirring in step V1, centrifuge at 8000 rpm for 10 min, wash the precipitate with deionized water, vacuum dry, disperse it in 0.1 M NaOH solution at a material-to-liquid ratio of 1 g: 50 mL, stir at room temperature for 10 min, filter, wash with distilled water, soak in 2 mg / mL polylysine aqueous solution for 11 h, filter under vacuum, wash the filter cake with distilled water, vacuum dry, and obtain lysine PLGA microspheres.
[0041] This embodiment also provides a method for preparing the airway stent coating composition for treating benign airway stenosis, comprising the following steps: S1. Mix deionized water and ethanol, add γ-aminopropyltriethoxysilane (APTES), and stir magnetically for 1 h to obtain an APTES solution. Immerse the silicone scaffold in anhydrous ethanol for 2 h, dry it under nitrogen, irradiate it under a vacuum UV lamp (photon energy 7.2 eV) for 200 s, immediately immerse it in the APTES solution, heat at 90 °C for 1 h, wash with ethanol, dry it under nitrogen, and react it in an oven at 110 °C for 5 min. The surface area ratio of the silicone scaffold to the volume ratio of the APTES solution is 1 cm³. 2 1 mL; the volume ratio of deionized water, ethanol and APTES is 1:18:1; S2. Prepare an NHS / EDCI solution by adding NHS and EDCI to deionized water. Dissolve modified glycyrrhizic acid in DMF solvent at a ratio of 10 mg / mL. Add the NHS / EDCI solution dropwise and stir for 2 h, adjusting the pH to 5 during the process. Add the silicone scaffold treated in step S1 and react for 12 h. Wash with deionized water and vacuum dry. The mass concentration of NHS in the NHS / EDCI solution in deionized water is 10 mg / mL. The mass ratio of modified glycyrrhizic acid, NHS, and EDCI is 1:0.5:0.8. S3. Add modified PLGA microspheres to deionized water, add the silicone stent treated in step S2, react for 12 h, rinse the surface with deionized water, and dry to obtain an airway stent coating composition for treating benign airway stenosis; the mass concentration of modified PLGA in deionized water is 10 mg / mL; the ratio of glycyrrhizic acid to APTES is 1 g:1.5 mL.
[0042] The only difference between Comparative Example 1 and Example 1 is that modified glycyrrhizic acid was not added.
[0043] The only difference between Comparative Example 2 and Example 1 is that after stirring in step V1, the mixture was centrifuged at 8000 rpm for 10 min, the precipitate was washed with deionized water, and then vacuum dried. The resulting product replaced the modified PLGA microspheres.
[0044] Experiment 1: New Zealand white rabbits weighing 2.5-3 kg, regardless of sex, were used to establish a benign airway stenosis animal model. The rabbits were anesthetized with 0.5 mL of sedative intramuscular injection. They were fixed on the experimental table, their skin prepared, disinfected, and draped. The skin and subcutaneous muscle were incised layer by layer to expose the trachea in the neck. A 1 cm transverse incision was made along the tracheal cartilage rings. A 6 mm diameter nylon brush was inserted through the incision to circumferentially destroy the tracheal mucosa 1 cm below the incision. The tracheal incision was sutured, and the subcutaneous tissue and skin were sutured layer by layer. The area was then disinfected and bandaged. A CT scan was performed one month later to establish the rabbit airway stenosis animal model. Animals with airway stenosis were randomly divided into 6 groups of 6. They were anesthetized with 0.5 mL of sedative intramuscular injection. Silicone stents treated with the compositions obtained in Examples 1-3 and Comparative Examples 1-2 were placed into the trachea using a stent pusher. 0.5 mL of the anesthetic recovery agent, chlorpheniramine, was administered intramuscularly. The degree of tracheal stenosis was measured one month after stent placement. Results are as follows: Figure 1 As shown.
[0045] Experimental Example 2: Silicone scaffolds obtained from Examples 1-3 and Comparative Examples 1-2 were cut into 1 cm lengths as samples. Staphylococcus aureus was cultured in LB medium at 37°C for 24 h, and the bacterial culture was diluted to 1×10⁻⁶ with sterile PBS. 6CFU / mL, 100 mL was added to the sample, and co-cultured at 37℃ for 12 h as the experimental group. An untreated silicone scaffold was used as the blank group. The co-cultured bacterial solution was coated onto agar medium and incubated at 37℃ for 12 h. The bacterial count was then performed, and the inhibition rate was calculated. The results are as follows: Figure 2 As shown.
[0046] Those skilled in the art should understand that the discussion of any of the above embodiments is merely exemplary and is not intended to imply that the scope of the invention is limited to these examples; within the framework of the invention, the technical features of the above embodiments or different embodiments can also be combined, the steps can be implemented in any order, and there are many other variations of the different aspects of the invention as described above, which are not provided in detail for the sake of brevity.
Claims
1. An airway stent coating composition for treating benign airway stenosis, characterized in that, The raw materials for preparation include the following components in parts by weight: 8-12 parts of modified glycyrrhizic acid, 6-9 parts of modified PLGA microspheres, and 2-3 parts of γ-aminopropyltriethoxysilane; The raw materials for preparing glycyrrhizic acid include the following components in parts by weight: 2-3 parts of glycyrrhizic acid monoammonium salt and 1-1.5 parts of periodic acid; The method for preparing glycyrrhizic acid includes the following steps: L1. Dissolve NaIO4 in ultrapure water to prepare a 0.1 g / mL NaIO4 aqueous solution. Add glycyrrhizic acid monoammonium salt to ultrapure water and stir at 60℃ and 300 rpm to dissolve. Add the NaIO4 aqueous solution dropwise under the protection of light. L2. After the addition of step L1 is completed, the reaction is stirred for 4 h, ethylene glycol is added, stirring is continued for 30 min, and the mixture is dialyzed in ultrapure water at 50℃ for 48 h. After freeze drying, modified glycyrrhizic acid is obtained. The raw materials for preparing the modified @PLGA microspheres include the following components in parts by weight: 2-3 parts pirfenidone, 6-9 parts polylactic acid-glycolic acid copolymer, and 5-8 parts polylysine; The preparation method of the PFD@PLGA microspheres includes the following steps: V1. Dissolve pirfenidone and PLGA in dichloromethane to obtain a PFD / PLGA mixture. Prepare a 0.4% w / v PVA aqueous solution. Add the PFD / PLGA mixture dropwise to the PVA solution. Homogenize at 5000 rpm for 5 min in an ice-water bath and stir at 500-600 rpm to evaporate the organic solvent. V2. After stirring in step V1, centrifuge at 8000 rpm for 10 min, wash the precipitate with deionized water, vacuum dry, disperse it in 0.1 M NaOH solution at a material-to-liquid ratio of 1 g: 50 mL, stir at room temperature for 10 min, filter, wash with distilled water, soak in 2 mg / mL polylysine aqueous solution for 10-12 h, filter under vacuum, wash the filter cake with distilled water, vacuum dry to obtain lysine PLGA microspheres.
2. The airway stent coating composition for treating benign airway stenosis according to claim 1, characterized in that, In step L1, the mass concentration of the glycyrrhizic acid monoammonium salt in ultrapure water is 50 mg / mL; the volume ratio of ethylene glycol to ultrapure water is 1:
25.
3. The airway stent coating composition for treating benign airway stenosis according to claim 2, characterized in that, In step V1, the mass-volume fraction of PLGA in DCM is 5% w / v; the mass ratio of PLGA to PVA is 4:
5.
4. A method for preparing an airway stent coating composition for treating benign airway stenosis as described in any one of claims 1-3, characterized in that, Includes the following steps: S1. Mix deionized water and ethanol, add γ-aminopropyltriethoxysilane, stir magnetically for 1 h to obtain APTES solution, soak the silicone scaffold in anhydrous ethanol for 2 h, dry it with nitrogen, irradiate it under a vacuum ultraviolet lamp for 200 s, immediately put it into APTES solution, heat at 90 °C for 1 h, wash with ethanol, dry with nitrogen, and react in an oven at 110 °C for 5 min. S2. Prepare an NHS / EDCI solution by adding NHS and EDCI to deionized water. Dissolve modified glycyrrhizic acid in DMF solvent at a ratio of 10 mg / mL. Add the NHS / EDCI solution dropwise and stir for 2 h. Adjust the pH to 5 during the process. Add the silicone scaffold treated in step S1 and react for 12 h. Wash with deionized water and dry under vacuum. S3. Add the modified PLGA microspheres to deionized water, add the silicone stent treated in step S2, react for 12 h, rinse the surface with deionized water, and dry to obtain the airway stent coating composition for treating benign airway stenosis.
5. A method for preparing the airway stent coating composition for treating benign airway stenosis according to claim 4, characterized in that, In step S1, the surface area of the silicone scaffold to the volume ratio of the APTES solution is 1 cm². 2 1 mL; the volume ratio of the deionized water, ethanol and APTES is 1:18:
1.
6. A method for preparing the airway stent coating composition for treating benign airway stenosis according to claim 5, characterized in that, In step S2, the mass concentration of NHS in the NHS / EDCI solution in deionized water is 10 mg / mL; the mass ratio of modified glycyrrhizic acid, NHS and EDCI is 1:0.5:0.
8.
7. A method for preparing the airway stent coating composition for treating benign airway stenosis according to claim 6, characterized in that, In step S3, the mass concentration of the modified PLGA in deionized water is 10 mg / mL; the ratio of modified glycyrrhizic acid to APTES is 1 g:1.5 mL.