Effect of nintedanib thermo-sensitive hydrogel on neovascularization in alkali burn rat model

AIM:To investigate the effects of nintedanib thermo-sensitive hydrogel(NTH)on neovascularization and related markers in corneal alkali burns of Wistar rats.METHODS:NTH was prepared by grinding,and its phase-transition temperature was determined.Thirty specific-pathogen-free Wistar rats served as a model of corneal alkali burn in the right eye were randomly divided into 3 groups(n=10,each):model group treated with 0.9%saline once a day,NTH group with 0.2%nintedanib b.i.d,and dexamethasone group with dexamethasone ointment once a day.The left eye of rats served as the controls.The corneal transparency was observed under a slit-lamp microscope,and the area of neovascularization was calculated.On day 7,the rats were sacrificed,and the cornea was removed and embedded with paraffin,then stained with hematoxylin一eosin,and the expression of vascular endothelial growth factor receptor 2(VEGFR-2)and CD31 in the corneal tissues of each group was detected by immunofluorescence.RESULTS:The phase-transition temperature ofnintedanib obtained by grinding was 37℃after adding artificial tears.The results of the alkali burn model indicated that the growth rate of neovascularization in the NTH group was slower than that in the model group,and the neovascularization area was significantly smaller than that in the model group(P<0.05).Moreover,CD31 and VEGFR-2 expression levels in the NTH group were significantly lower than those in the model group.CONCLUSION:NTH becomes colloidal at body temperature,which is beneficial for releasing the drug slowly and can significantly inhibit the neovascularization of corneal induced by alkali burn in rats.

Nintedanib induces apoptosis in human pterygium cells through the FGFR2-ERK signalling pathway

AIM:To investigate whether nintedanib can inhibit pterygium cells through the fibroblast growth factor receptor 2(FGFR2)/extracellular-signal-regulated kinase(ERK)pathway.METHODS:Human primary pterygium cells were cultured in vitro.After treatment with nintedanib,the cell morphology was observed under microscopy,the morphological changes of the nucleus were observed after DAPI staining,apoptosis was analyzed by Annexin-V FITC/PI double staining,and the changes of apoptosis-associated proteins were detected by Western blot.The binding ability of nintedanib to FGFR2 was predicted by molecular docking.Finally,by silencing FGFR2,we explored whether nintedanib inhibited FGFR2/ERK pathway.RESULTS:The results showed that nintedanib inhibited the growth of pterygium cells and caused nuclear pyknosis.The results of Annexin-VFITC/PI double staining showed that nintedanib was able to induce early and late apoptosis of pterygium cells,significantly increasing the expression of apoptosis-associated proteins Bax and cleaved-Caspase3(P<0.05),and reducing the expression of Bcl-2(P<0.05).In addition,nintedanib significantly inhibited ERK1/2 phosphorylation through FGFR2(P<0.05).After silencing the expression of FGFR2,there was no significant difference in the inhibition of ERK1/2 phosphorylation by nintedanib(P>0.05).CONCLUSION:Nintedanib induces apoptosis of pterygium cells by inhibiting FGFR2/ERK pathway.

Inhibition of corneal neovascularization by topical application of nintedanib in rabbit models

AIM:To evaluate the potential efficacy and mechanisms of nintedanib in corneal neovascularization(NV)in rabbit models.METHODS:Corneal NV was induced using 1 mol/L Na OH.Rabbits(n=21)were randomized to 3 groups:Group 1 were treated with 0.9%NaCl,Group 2 with Avastin(5 mg/mL),and Group 3 with nintedanib(1 mg/mL).All treatments star ted 1 d af ter alkaline burns and were topically performed 3 times a day for 2 wk.Photographs were taken on a slit lamp microscope on day 7 and 14.The NV area,the length of the vascularization and angiogenesis index(AI)were used to evaluate the corneal NV.On day 14,the immunohistochemical(IHC)studies of the cornea were examined.Western blot was performed to test the expression levels of vascular endothelial growth factor(VEGF),Akt,p-Akt,P38,p-P38,MMP-2 and MMP-9.RESULTS:The corneal NV area,vessel length and AI in Group 3 were significantly lower than Group 2,with both being lower than Group 1.IHC staining showed that VEGF was significantly overexpressed in the epithelium and stroma of cornea following alkaline burns.In contrast,the level of VEGF was significantly suppressed in both Group 2 and Group 3.Western blot results further confirmed that,compared with Group 1,Group 3 had significantly reduced expressions of VEGF,Akt,p-Akt,p-P38,MMP-2,and MMP-9 in corneal tissues.Trends of lower levels of MMP-2,AKT,and p-AKT in Group 3 than Group 2 were identified.CONCLUSION:Nintedanib and Avastin can effectively inhibit corneal NV,with P38 MAPK and AKT signaling pathways being possibly involved.Nintedanib seems more effective than Avastin and has the potential to be a novel therapy for preventing corneal NV.

Evaluation of nintedanib as a new postoperative antiscarring agent in experimental extraocular muscle surgery

AIM:To investigate the efficacy of nintedanib on reducing postoperative inflammation,fibrosis and adhesion formation following extraocular muscle surgery in rabbits in comparison with triamcinolone acetonide(TA).METHODS:Reinsertion of superior rectus muscle in right eyes of 30 New Zealand white rabbits were performed.They were randomized to receive one of the following treatments:0.9%normal saline,one of 1-,5-,and 10μmol doses of nintedanib subconjunctivally immediately after surgery and on postoperative day 1,2,3,5,and 7,and TA immediately after surgery.As a control group,unoperated left eyes(n=6)were used.On the 28 th day,six eyes from each group were enucleated and histopathologically and immunohistochemically analyzed to assess the postoperative inflammatory changes,fibrosis and adhesion.Transforming growth factor beta,matrix metalloproteinase-2 and alpha smooth muscle actin expressions were evaluated.RESULTS:Conjunctival and scleral inflammation in TA and nintedanib groups were significantly reduced compared to saline(sham)group.Conjunctival vascularity and rectus muscle fibrosis were significantly reduced in 10μmol nintedanib group.Nintedanib groups were the most effective groups in reduction of perimuscular fibrosis.Neither three nintedanib groups nor TA group differed statistically from sham group with regard to adhesion.The expressions of transforming growth factor beta,alpha smooth muscle actin and matrix metalloproteinase-2 were reduced in nintedanib groups compared to saline group.CONCLUSION:Nintedanib appears to attenuate postoperative inflammation and fibrosis after extraocular muscle surgery.Nintedanib may be a safer and stronger alternative agent in extraocular muscle surgery when compared to steroids.Further investigation is needed to prove antiadhesive effect of nintedanib.

Effect of a novel tyrosine kinase inhibitor nintedanib on bFGF and VEGF concentrations in a rabbit retinal vein occlusion model

AIM:To evaluate whether a novel tyrosine kinase inhibitor nintedanib could inhibit basic fibroblast growth factor(bFGF)and vascular endothelial growth factor(VEGF)simultaneously for retinal vascular disease in vivo.METHODS:After a laser induced rabbit retinal vein occlusion(RVO)model was made,0.5 mg of nintedanib was injected intravitreally in the left eye on the third day while the right eye was as a control.Intracameral samples were taken on the day before laser treatment and days 1,3,7,14,21,and 28 after treatment.Enzyme-linked immunosorbent assay(ELISA)was used to test the bFGF and VEGF-A concentrations in the aqueous humor.RESULTS:Both bFGF and VEGF-A rose significantly on the third day after laser treatment in both eyes.In the control eye the bFGF concentration peaked on the 14th day while the VEGF-A concentration dropped rapidly soon after the third day.After nintadanib injection in the study eye,both bFGF and VEGF-A showed a significant reduction on the 4th day(7th day after laser treatment)when compared to the control eye,and kept on low level in the following several weeks.CONCLUSION:Intravitreal injection of nintedanib can inhibit the expression of bFGF and VEGF in the process of RVO model to a certain extent,which is expected to become a new method for the treatment of retinal vascular diseases or fibrotic diseases.

Nintedanib对Ang Ⅱ诱导肾脏成纤维细胞产生细胞外基质的拮抗作用

目的探讨尼达尼布(Nintedanib)对抗血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)诱导的肾脏成纤维细胞产生细胞外基质的作用及其机制。方法 AngⅡ处理大鼠肾脏成纤维细胞(NRK-49F),Western印迹法检测相关分子的蛋白表达量,DHE荧光探针法检测活性氧簇(ROS)的水平。结果肾脏成纤维细胞中AngⅡ通过诱导PI3K/Akt信号通路的激活,引起纤维连接蛋白和胶原蛋白Ⅰ的积聚。Nintedanib能抑制AngⅡ诱导的PI3K/Akt信号通路的激活。Nintedanib还可以抑制AngⅡ引起的ROS水平升高。结论 Nintedanib可以抑制AngⅡ诱导的ECM成分升高,其作用机制与其抑制PI3K/Akt激活并抑制ROS产生有关。

Nintedanib对碱烧伤大鼠角膜新生血管的抑制作用

目的:探讨尼达尼布(Nintedanib)对大鼠角膜碱烧伤后新生血管的抑制作用。方法:将SD大鼠角膜碱烧伤动物模型随机分成5组,每组各6只。A组、B组与C组分别给予0.2%,0.05%,0.02%的Nintedanib滴眼液滴眼,D组给予0.1%地塞米松滴眼液,E组给予生理盐水滴眼,每组每天4次滴眼治疗,共14 d。分别于碱烧伤后第3,7,14天观察角膜新生血管(corneal neovascularization,CNV)情况,计算CNV面积在角膜面积中的占比(C/N)。于碱烧伤后第14天处死全部大鼠,HE染色大鼠角膜进行组织学观察,并通过免疫荧光法检测各组VEGFR-2和CD31蛋白的表达情况。结果:大鼠角膜碱烧伤后的第3,7,14天,A组、B组、C组和D组的C/N均小于E组,差异均有统计学意义(均P<0.05);B组与D组各时间点C/N面积的差异均无统计学意义(均P>0.05),但这两组与A组比较,或者与C组比较,差异均有统计学意义(均P<0.05)。HE染色及免疫组织化学染色结果显示:角膜碱烧伤后第14天,各组角膜VEGFR-2和CD31蛋白表达增强,与A组、B组、D组比较,C组、E组CNV旺盛致密,炎症细胞更多,角膜水肿跟明显,VEGFR-2和CD31蛋白表达较强,在表达较弱的三组里,A组的CNV最少。结论:Nintedanib对碱烧伤后大鼠CNV形成具有抑制作用,且0.2%Nintedanib的治疗效果最佳。

Nintedanib:抗癌、抗肺纤维化的三联血管激酶抑制剂

血管生成被认为是癌症治疗的潜在靶向机制,血管内皮生长因子(VEGF)、血小板源生长因子(PDGF)、纤维母细胞生长因子(FGF)均为与血管生成相关的多能生长因子。勃林格殷格翰公司开发的新药nintedanib,2014年10月被FDA批准上市。其作为一种作用于VEGFR、PDGFR、FGFR的小分子三联血管激酶抑制剂,用于治疗特发性肺纤维化(IPF),肝衰竭和癌症,包括转移性非小细胞肺癌(NSCLC)、卵巢癌、前列腺癌和结肠癌、肾细胞癌等,在临床前研究中表现出独特药理作用,在一系列临床研究中显示出良好的治疗前景,且安全性及耐受性均较好。

吡非尼酮和尼达尼布对156例特发性肺纤维化患者的临床效果及对肺功能的影响

目的研究吡非尼酮和尼达尼布对特发性肺纤维化(IPF)患者的临床治疗效果及对肺功能相关指标的影响。方法选择2019年至2022年间,我院呼吸与危重症医学科收治的156例IPF患者,随机分成乙酰半胱氨酸对照组(n=48)、吡非尼酮观察组(n=51)和尼达尼布观察组(n=57),观察组分别给予吡非尼酮或尼达尼布进行治疗,对照组患者按照常规方法给药乙酰半胱氨酸治疗,疗程为48周。比较三组药物对IPF患者治疗前后的用力肺活量(FVC)、一秒量(FEV_(1))、一氧化碳弥散量占预计值比例(D_(L)CO%pred)指标的影响;检测血清涎液化糖链抗6(KL-6)、干扰素-γ、白介素-6(IL-6)和乳酸脱氢酶(LDH)表达;统计圣乔治呼吸问卷(St.George’s Respiratory Questionnaire,SGRQ)评分、复发率以及生存曲线。结果治疗48周后,吡非尼酮和尼达尼布观察组患者的FVC和FVC%pred指标较对照组相比均有统计学差异(P<0.05),尼达尼布观察组治疗48周后,FVC较对照组下降140 mL/年,吡非尼酮观察组较对照组下降110 mL/年,两观察组之间无统计学差异(P>0.05);对照组治疗前后患者的血清KL-6值和干扰素-γ值无统计学差异,而吡非尼酮和尼达尼布两观察组治疗前后患者血清KL-6和干扰素-γ值均显著下降(P<0.05),三组患者治疗前后的IL-6和LDH表达变化均无统计学差异(P>0.05)。治疗48周后随访,对照组患者急性发作率为45.83%,吡非尼酮观察组患者急性发作率为23.53%,尼达尼布观察组患者急性发作率为22.81%;治疗后两观察组患者的SGRQ评分显著降低,生活质量具有明显优势。结论吡非尼酮或尼达尼布均可延缓IPF患者肺功能下降,降低患者血清KL-6和干扰素-γ水平,治疗效果显著,治疗方案对临床使用具有重要的指导作用。

吸入用pH敏感型尼达尼布脂质体的制备与优化

目的设计pH敏感的尼达尼布脂质体(Nb-Lips),使其靶向肺纤维化的酸性微环境。通过处方工艺优化Nb-Lips包封率(EE%)。方法采用薄膜水化法制备Nb-Lips,以EE%为指标通过单因素考察、响应面法对脂质体处方进行优化。通过动态光散射技术和微柱离心法考察其粒径、分散系数(PDI)、Zeta电位、EE%;采用透析法分别考察Nb-Lips在pH值为7.4、5.3的人工肺液中的体外释放行为;使用压缩空气式雾化器雾化Nb-Lips,并考察其雾化稳定性及空气动力学粒径。结果Nb-Lips粒径为(100.651±7.315)nm,PDI为(0.328±0.026),Zeta电位为(21.633±2.004)mV,优化后的EE%>80%。与在pH值为7.4的人工肺液中比较,Nb-Lips在pH值为5.3的人工肺液中总释放量高60.78%,且释放时间达48 h,远高于尼达尼布溶液。Nb-Lips雾化前后粒径、电位、PDI无显著差异,EE%下降4.25%,雾化后液滴微细粒子分数为37.49%。结论响应面法优化处方工艺有效地提高Nb-Lips EE%,成功制备酸性环境敏感的、可吸入、可缓慢释放的Nb-Lips。

1例尼达尼布致肺癌合并间质性肺炎患者急性肝损伤的药学实践

本文报道临床药师参与1例肺癌合并间质性肺炎患者使用尼达尼布致急性肝损伤的治疗过程。临床药师通过梳理患者既往用药史,复习国内外相关文献,并对患者肝酶急速升高情况进行分析,根据RUCAM量表判定该病例发生的急性肝损伤与尼达尼布的关联性为“很可能有关”,建议停用尼达尼布,并积极给予保肝治疗。临床医师采纳建议,治疗20 d后患者肝功能好转。临床药师分析患者肝损伤的原因和特点,协助医师及时识别处理不良反应,参与临床实践,体现了自身价值。本文可为同类型急性肝损伤病例的诊疗提供参考。

尼达尼布治疗结缔组织相关性间质性肺炎临床疗效研究

目的:评估尼达尼布联合常规治疗对结缔组织相关性间质性肺炎(CTD-ILD)的疗效。方法:收集102例CTD-ILD患者作为研究对象,根据临床治疗方案不同将其分为常规治疗组(50例)和尼达尼布联合治疗组(52例),疗程6个月。比较2组患者治疗前、治疗6个月后临床症状、肺功能、肺部高分辨CT评分及血清细胞因子水平的变化。结果:尼达尼布联合治疗组血清细胞因子、肺部高分辨CT评分较治疗前明显降低,肺功能明显改善(P均<0.05)。结论:尼达尼布联合常规糖皮质激素抗炎治疗可降低CTD-ILD患者血清细胞因子水平,减轻体内炎症反应,改善肺功能,有助于延缓CTD-ILD患者的肺纤维化进展。

尼达尼布纳米脂质体的制备及其表征研究

目的探讨4种不同方法制备尼达尼布脂质体的关键理化特性,筛选出尼达尼布脂质体的最佳制备方法。方法采用薄膜分散法、逆向蒸发法、乙醇注入法和改良版乙醇注入法制备尼达尼布脂质体;利用透析法测定尼达尼布脂质体的包封率,并进行粒径大小、分散性、表面电位和形貌表征,在室温放置7 d后评估其稳定性。结果薄膜分散法、逆向蒸发法、乙醇注入法和改良版乙醇注入法均制备了类圆形尼达尼布脂质体,粒径大小分别为(285.1±12.3)、(271.4±5.9)、(226.3±14.8)、(197.2±11.2)nm;包封率分别为(15.82±1.26)%、(16.71±1.35)%、(25.12±3.21)%和(32.5±3.61)%;与其他3种方法相比,改良版乙醇注入法制备尼达尼布脂质体粒径大小显著减小,包封率显著增加(P<0.05)。室温放置7 d后,薄膜分散法和逆向蒸发法粒径明显增大(P<0.01),乙醇注入法和改良版乙醇注入法粒径大小无明显差异(P>0.05)。结论改良版乙醇注入法制备的尼达尼布脂质体关键理化特性表现优异,可作为制备尼达尼布脂质体的优选方法。

靶向药在瘢痕疙瘩治疗中的研究进展及应用前景

瘢痕疙瘩(KD)是皮肤在创伤修复过程中成纤维细胞过度增殖和细胞外基质过量沉积所形成的一种病理性瘢痕,影响外观的同时常伴有瘙痒和疼痛,严重影响患者的生活质量。治疗方法多种多样,如注射、激光和手术等,但效果并不理想。目前,尝试用于治疗瘢痕疙瘩的靶向药包括大分子单克隆抗体度普利尤单抗(Dupilumab),小分子靶向药物尼达尼布(Nintedanib)、舒尼替尼(Sunitinib)和索拉非尼(Sorafenib)等,这些靶向药的使用为未来瘢痕疙瘩的防治提供新思路新方法。本文综述以上靶向药在瘢痕疙瘩治疗中的研究进展,并展望其应用前景。

电感耦合等离子体质谱法测定乙磺酸尼达尼布原料药中7种杂质元素

建立了电感耦合等离子体质谱(ICP-MS)法测定乙磺酸尼达尼布原料药中镉、铅、砷、汞、钴、钒、镍7种元素杂质。用微波消解法进行样品处理,以ICP-MS法进行测定,射频功率为1550 W,雾化气流量为1.1 L/min,测定模式为碰撞池模式,碰撞气流量为4.8 L/min,冷却气流量为14 L/min,辅助气流量为0.8 L/min,蠕动泵转速为40 r/min。7种元素的质量浓度在线性范围内与各自的信号值线性关系良好,相关系数均不小于0.9999;检测限为0.0002~0.0060μg/g;定量限为0.001~0.019μg/g;重复性试验结果的相对标准偏差为0.7%~1.2%(n=6);各浓度点平均回收率为82.6%~119.1%(n=3)。该方法灵敏度高,准确性好,适用于乙磺酸尼达尼布原料药中元素杂质的检测。

ICP-MS法测定乙磺酸尼达尼布原料药中催化剂钯的残留量

建立了电感耦合等离子体质谱(ICP-MS)法测定乙磺酸尼达尼布中催化剂钯(Pd)的残留量。样品采用微波消解法进行处理;以ICP-MS法进行测定,射频功率为1550 W,雾化气流量为1.1 L/min,测定模式为碰撞池模式(KED),碰撞气流量为4.8 L/min,冷却气流量为14 L/min,辅助气流量为0.8 L/min,蠕动泵转速为40 r/min。Pd元素标准曲线的相关系数为0.9999;检测限为0.028μg/g;定量限为0.083μg/g;重复性试验RSD为2.8%(n=6);中间精密度试验RSD为2.9%(n=12);各浓度点平均回收率均在95.4%~98.3%(n=3),均满足USP<233>方法学验证的要求。乙磺酸尼达尼布原料药检测的结果小于国际人用药物注册技术协调会议《元素杂质指导原则Q3D》(ICH Q3D)中Pd元素的每日允许暴露量(PDE)。该方法灵敏度高、准确性好,适用于乙磺酸尼达尼布原料药中催化剂钯的残留量检测。

尼达尼布治疗进展性肺纤维化的疗效分析

目的探讨进展性肺纤维化(progressive pulmonary fibrosing,PPF)患者应用尼达尼布治疗的临床效果及安全性分析。方法回顾性分析2022年6月至2023年10月在锦州医科大学附属第一医院住院确诊为PPF的患者的临床资料(80例),依据是否应用尼达尼布治疗分为常规治疗组37例和尼达尼布治疗组43例,均通过完善检查明确病因,并给予病因治疗及对症治疗,尼达尼布治疗组在此基础上给予联合尼达尼布治疗。比较两组患者治疗前和治疗6个月后的肺功能DLCO%、FVC%指标、PaO_(2)、六分钟步行试验(6 minute walking test,6MWT)距离、胸部HRCT评分和不良反应发生率。结果尼达尼布治疗组患者FVC%、DLCO%、PaO_(2)以及6MWT距离优于常规治疗组(P<0.05)。尼达尼布组的FVC%、DLCO%下降率低于常规治疗组(P<0.05)。胸部HRCT评分方面,尼达尼布治疗组治疗后的评分低于常规治疗组,差异具有统计学意义(P<0.05),表明尼达尼布有助于延缓PPF的进展。在安全性评价方面,经过6个月的治疗及观察,两组患者不良反应的发生率无明显差异(P>0.05)。结论尼达尼布治疗能够延缓PPF患者肺功能的下降速度。延缓肺纤维化进展,提高生活质量且治疗期间未增加不良反应发生率。

尼达尼布联合低分子肝素治疗对肺间质纤维化患者的影响

目的:观察尼达尼布联合低分子肝素治疗对肺间质纤维化患者的影响。方法:选取2022年1月—2023年12月临泽县人民医院呼吸与危重症医学科收治的80例肺间质纤维化患者作为研究对象,按照随机数表法分为研究组和对照组,各40例。对照组采用低分子肝素治疗,研究组则在对照组基础上联用尼达尼布治疗,比较两组的临床疗效、炎症因子、肺功能指标、运动耐量、肺间质纤维化指标、动脉血气指标。结果:研究组治疗总有效率高于对照组,差异有统计学意义(P<0.05)。治疗后,观察组第1秒用力呼气容积(FEV1)、用力肺活量(FVC)、动脉血氧分压(PaO_(2))、动脉血氧饱和度(SaO_(2))、氧合指数(PaO_(2)/FiO_(2))及6分钟步行试验(6MWT)评分均高于对照组,且Ⅲ型胶原(C-Ⅲ)、层粘连蛋白(LN)、透明质酸(HA)、动脉血二氧化碳分压(PaCO_(2))和白细胞介素-6(IL-6)、降钙素原(PCT)、C反应蛋白(CRP)水平低于对照组,差异有统计学意义(P<0.05)。结论:达尼布与低分子肝素联合治疗肺间质纤维化效果较好,能够显著改善患者动脉血气指标和炎症刺激,提高肺功能,抑制肺间质纤维化,改善运动耐量,治疗实用性较高。

吡非尼酮和尼达尼布治疗特发性肺纤维化的间接Meta分析

目的 系统评价吡非尼酮和尼达尼布治疗特发性肺纤维化的临床有效性和安全性。方法 在中国知网、万方、维普网、PubMed、Cochrane library等数据库对吡非尼酮和尼达尼布治疗特发性肺纤维化的中英文公开发表的随机对照研究进行检索,检索时间为2000年1月—2021年12月。用间接Meta分析的方法对已有研究进行合并,系统评价两种药物治疗特发性肺纤维化的有效性和安全性。结果 共纳入15项随机对照研究,其中吡非尼酮试验组1 026例、对照组845例,尼达尼布试验组1 864例、对照组1 848例,两对照组均为安慰剂。间接Meta分析结果显示,在病情急性加重率、用力肺活量比基线下降≥10%或绝对值下降≥0.2 L发生率这两项疗效评价指标方面,两药表现相似(间接分析结果均P>0.01,差异无统计学意义);在病情进展率方面,尼达尼布150 mg(bid)优于吡非尼酮800 mg(tid)(RR=1.66,95%CI为1.06~2.63)。安全性方面,尼达尼布150 mg(bid)的腹泻发生率高于吡非尼酮800 mg(tid)(RR=0.42,95%CI为0.33~0.53)。结论 尼达尼布与吡非尼酮相比,在控制疾病进展方面略占优势,但不良反应发生率也同时增加。

特发性肺纤维化药物治疗的研究进展

特发性肺纤维化(IPF)是一种慢性、渐进性的细胞间质病,病因和发病机制尚不明确。2种或2种以上药物联合使用可减少药物使用剂量,减轻不良反应,增加治疗靶通路,是目前IPF研究的关注热点。吡非尼酮和尼达尼布是FDA首次批准治疗IPF的多靶点治疗药物,其联合用药正处于临床试验阶段。本文对IPF的多靶点治疗进展进行综述,进一步讨论联合用药的利弊,浅谈中医在治疗IPF中的优势。