CN115300627B - 钠-葡萄糖共转运蛋白2抑制剂的应用、一种药物组合物及其应用 - Google Patents
钠-葡萄糖共转运蛋白2抑制剂的应用、一种药物组合物及其应用 Download PDFInfo
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Abstract
本发明涉及骨关节炎的预防和治疗技术领域,具体涉及钠‑葡萄糖共转运蛋白2抑制剂的应用、一种药物组合物及其应用,该药物组合物中含有两者以上混合保存或者各自独立保存的组分A和组分B,所述组分A为钠‑葡萄糖共转运蛋白2抑制剂,所述组分B为透明质酸和/或非甾体抗炎药。本发明提供的药物组合物能够保护软骨细胞和软骨,缓解由骨关节炎引起的相关软骨退变,减轻由骨关节炎引起的疼痛症状,抑制由骨关节炎引起的滑膜炎,并降低骨关节炎患者关节置换的风险,能够预防和治疗骨关节炎。
Description
技术领域
本发明涉及骨关节炎的预防和治疗技术领域,具体涉及钠-葡萄糖共转运蛋白2抑制剂的应用、一种药物组合物及其在制备药物中的应用。
背景技术
骨关节炎(Osteoarthritis,OA)是一种以关节软骨退变、软骨下骨硬化和骨赘形成为主要特点的关节退行性疾病,并以活动后关节疼痛、活动受限和关节变形为其主要临床表现,常累及负重关节。
2015年世界卫生组织调查显示:60岁以上男性和女性的症状学OA患病率分别为18.0%和9.6%,其中80%的患者行动受限,25%的患者无法独立完成日常活动。中国流行病学调查研究显示,65岁以上人群中OA的患病率超过50%,约80%的OA患者存在一定程度的运动受限,25%的OA患者日常生活受到明显影响,疾病进展到晚期往往需要进行人工关节置换,虽然关节置换手术技术已日趋成熟,但仍存在一定风险,且费用昂贵。
目前,国内外尚无明确有效且安全的可延缓OA病情进展的药物。最新的国际OA权威指南明确提出,许多一直以来被广泛用于治疗OA的药物,如透明质酸、氨基葡萄糖、硫酸软骨素和双醋瑞因等,由于最新的高质量的循证医学证据的出现,其有效性在世界范围内引起了广泛的争议,甚至被认定为疗效不确定或不推荐使用(McAlindon T E,etc.,Osteoarthritis and Cartilage,2014,22(3):363-388)。
此外,由于OA患者多为中老年人,身体基础情况较差,常伴有其它系统疾病,如消化系统以及心血管系统疾病,而OA的一线治疗药物(症状缓解)如非甾体类抗炎药(Non-steroidal antiinflammatory drugs,NSAIDs)的使用易引起胃肠道副作用和心血管事件风险的增加,因此,亟待探索出针对早中期OA患者的安全有效的预防和治疗的药物。
发明内容
本发明的目的是为了解决现有的预防和/或治疗OA的技术存在的尚无明确有效且安全的可延缓OA病情进展的药物的问题。
为了实现上述目的,本发明的第一方面提供钠-葡萄糖共转运蛋白2抑制剂(SGLT2i)在制备药物中的应用,该药物为具有选自保护软骨细胞的功能、保护软骨的功能、缓解由骨关节炎引起的软骨退变的功能、减轻由骨关节炎引起的疼痛症状的功能、抑制由骨关节炎引起的滑膜炎的功能、降低骨关节炎患者关节置换的风险的功能、预防骨关节炎的功能和治疗骨关节炎的功能中的至少一种功能的药物。
本发明的第二方面提供一种药物组合物,该药物组合物中含有两者以上混合保存或者各自独立保存的以下组分:
组分A和组分B,所述组分A为SGLT2i,所述组分B为用于透明质酸和/或非甾体抗炎药。
本发明的第三方面提供上述第二方面所述的药物组合物在制备药物中的应用,该药物为具有选自保护软骨细胞的功能、保护软骨的功能、缓解由骨关节炎引起的软骨退变的功能、减轻由骨关节炎引起的疼痛症状的功能、抑制由骨关节炎引起的滑膜炎的功能、降低骨关节炎患者关节置换的风险的功能、预防骨关节炎的功能和治疗骨关节炎的功能中的至少一种功能的药物。
本发明所述的SGLT2i能够降低骨关节炎发病的风险,本发明首次发现SGLT2i对骨关节炎的发生和进展均具有保护作用,能够用于保护软骨细胞和软骨,缓解由骨关节炎引起的软骨退变,减轻由骨关节炎引起的疼痛症状,抑制由骨关节炎引起的滑膜炎,并降低骨关节炎患者关节置换的风险,能够预防和治疗骨关节炎。
本发明的其它特征和优点将通过随后的具体实施方式部分予以详细说明。
附图说明
图1为SGLT2i组与其他降糖药物组中髋或膝关节置换手术累积发生率曲线图;图1中a为其他降糖药物组中髋或膝关节置换手术累积发生率曲线,b为SGLT2i组中髋或膝关节置换手术累积发生率曲线;
图2为不同干预处理后小鼠膝关节软骨退变情况图;
图3为不同干预处理后小鼠膝关节软骨退变情况图,其中,图3A为不同干预处理后小鼠膝关节软骨中股骨的OARSI评分结果图,图3B为不同干预处理后小鼠膝关节软骨中胫骨的OARSI评分结果图;
图4为不同干预处理后小鼠膝关节软骨中MMP13和ADAMTS-5免疫组化染色情况图;
图5为不同干预处理后小鼠膝关节软骨中MMP13和ADAMTS-5的定量结果图;其中,图5A为不同干预处理后小鼠膝关节软骨中MMP13蛋白表达的定量结果图,图5B为不同干预处理后小鼠膝关节软骨中ADAMTS-5蛋白表达的定量结果图;
图6为不同干预处理后大鼠疼痛行为学结果图,其中,图6A为不同干预处理后大鼠疼痛阈值检测结果图,图6B为不同干预处理后大鼠双足负重差值检测结果图;
图7为不同干预处理后大鼠膝关节滑膜HE染色情况图;
图8为不同干预处理后大鼠膝关节滑膜炎评分结果图。
具体实施方式
在本文中所披露的范围的端点和任何值都不限于该精确的范围或值,这些范围或值应当理解为包含接近这些范围或值的值。对于数值范围来说,各个范围的端点值之间、各个范围的端点值和单独的点值之间,以及单独的点值之间可以彼此组合而得到一个或多个新的数值范围,这些数值范围应被视为在本文中具体公开。
如前所述,本发明的第一方面提供了SGLT2i在制备药物中的应用,该药物为具有选自保护软骨细胞的功能、保护软骨的功能、缓解由骨关节炎引起的软骨退变的功能、减轻由骨关节炎引起的疼痛症状的功能、抑制由骨关节炎引起的滑膜炎的功能、降低骨关节炎患者关节置换的风险的功能、预防骨关节炎的功能和治疗骨关节炎的功能中的至少一种功能的药物。
如前所述,本发明的第二方面提供了一种药物组合物,该药物组合物中含有两者以上混合保存或者独立保存的以下组分:
组分A和组分B,所述组分A为SGLT2i,所述组分B为透明质酸和/或非甾体抗炎药。
优选地,在所述药物组合物中,所述组分A与所述组分B的含量重量比为1:0.2-1。
优选地,所述SGLT2i选自达格列净、恩格列净和坎格列净中的至少一种。
优选地,所述非甾体抗炎药选自阿司匹林、布洛芬、塞来昔布、对乙酰氨基酚、双氯芬酸钠、萘普生、美洛昔康、吲哚美辛中的至少一种。
优选情况下,该药物组合物中还含有赋形剂,所述组分A和所述赋形剂的含量重量比为1:10-100。
优选地,所述赋形剂选自无水乳糖、硬脂酸镁、微晶纤维素、淀粉乙醇酸钠、硬脂酸中的至少一种。
优选地,该药物组合物的剂型为口服剂型或注射剂型。
更加优选地,所述剂型选自针剂、片剂、胶囊剂、冲剂、颗粒剂中的至少一种。
如前所述,本发明的第三方面提供了由前述第二方面所述的药物组合物在制备药物中的应用,该药物具有选自保护软骨细胞的功能、保护软骨的功能、缓解由骨关节炎引起的软骨退变的功能、减轻由骨关节炎引起的疼痛症状的功能、抑制由骨关节炎引起的滑膜炎的功能、降低骨关节炎患者关节置换的风险的功能、预防骨关节炎的功能和治疗骨关节炎的功能中的至少一种功能的药物。
优选地,所述骨关节炎选自膝关节关节炎、髋关节关节炎、踝关节关节炎、肩关节关节炎、肘关节关节炎和手关节关节炎中的至少一种。
以下将通过实例对本发明进行详细描述。
本发明中所有动物实验方案已经中南大学湘雅医院动物实验伦理委员会审核通过,且所有的实验都严格按照动物伦理准则和已被批准的动物实验制度设计进行。
本发明中实验所需的雄性12周龄C57BL/6J小鼠和8周龄SD大鼠均购自湖南斯莱克景达公司,并在标准环境下(维持昼夜节律、标准动物实验笼及自由进食等)饲养动物。
本发明中实验所用SGLT2i药物为(AstraZeneca),购自中南大学湘雅医院。
以下实例中的研究方法如下:
(1)研究对象
本研究纳入了1630名40岁以上的参与者,排除既往患有癌症以及发生了髋或膝关节置换手术的患者。
(2)SGLT2i服药情况的确定
通过药物代码来识别首次服用SGLT2i或其他降糖药物(利格列汀、阿格列汀、沙格列汀、维格列汀或西格列汀)的患者。
SGLT2i组为治疗组,其他降糖药物为对照组。“首次服用”的定义为进入队列之后的降糖药物的首次处方,即排除了进入研究队列之前具有SGLT2i或其他降糖药物处方史的研究对象。
(3)结局的确定
本研究的结局是在随访期间新发的髋或膝关节置换手术,通过疾病代码进行识别和定义。
(4)统计学分析
本研究是基于1:1倾向性评分匹配队列研究来比较SGLT2i组与其他降糖药物组发生髋或膝关节置换手术的风险。
比较了两组基线的特征,定量资料采用均数和标准差进行统计描述,定性资料采用百分比进行统计描述。
倾向性评分模型中包括的混杂因素为:一般人口学资料(年龄、性别与汤森剥夺指数),生活习惯信息(吸烟情况和饮酒情况),体重指数,以及药物使用情况。
每个研究对象的随访人年数是从治疗日期至以下事件中第一个发生的事件日期来计算:髋或膝关节置换手术,死亡,年满90岁,失访或随访结束(即,2018年12月31日)。
本研究采用Cox比例风险回归模型来评估SGLT2i组与其他降糖药物组相比发生髋或膝关节置换手术的风险,并计算出风险比(hazard ratio,HR)及其95%可信区间(confidence interval,CI)。此外,本研究进行了一项敏感性分析以减少偏倚,以排除在治疗日期后三个月内发生了髋或膝关节置换手术的患者,进而确保患者在治疗日期后立即发生的髋或膝关节置换手术不是因为服药导致的。
所有统计分析均采用SAS 9.4软件进行,P<0.05时可认为差异具有统计学意义,检验均为双侧检验。
实施例1:结果记录
本研究共纳入1630人(两组各815人),包括820名男性和810名女性,平均年龄为63.7±8.8岁。总体而言,两组人群通过IPW后的人群基本特征的均衡性较好,所有混杂因素的标准差均<0.1,详见表1。
Cox比例风险回归分析结果显示,在整个随访过程中,SGLT2i组发生了14例髋或膝关节置换手术,发生率为7.66/1000人年;其他降糖药物组发生了29例髋或膝关节置换手术,发生率为17.51/1000人年。SGLT2i组相比其他降糖药物组髋或膝关节置换手术发生的率差为-0.97/1000人年,HR值为0.45(95%CI:0.24至0.85,P=0.014)。
敏感性分析结果显示无实质性改变,HR值为0.48(95%CI:0.25至0.94,P=0.033)。
其中,发生率=各组发生髋或膝关节置换手术的人数/各组人群的随访时间之和。
实施例2:
1、骨关节炎模型的建立
采用内侧半月板失稳术(destabilisation of the medial meniscu,DMM)方法切断57BL/6J小鼠右后肢的内侧半月板板胫韧带作为实验组,以及仅切开57BL/6J小鼠右后肢的关节囊作为假手术组。
采用膝关节注射碘乙酸钠(mono-iodoacetate,MIA)方法向SD大鼠右后肢的膝关节腔内注射50μLMIA(浓度为3mg/50μL)作为实验组,以及向SD大鼠的右后肢的膝关节腔内注射50μL生理盐水作为假手术组。
2、实验分组
2.1、将50只57BL/6J小鼠随机分成5组,每组10只,具体分组情况如下:
1)假手术组:仅进行假手术处理;
2)生理盐水灌胃组:对行DMM术构建膝关节骨关节炎模型后3天的小鼠予以生理盐水(1μL/g)灌胃处理,每天1次;
3)SGLT2i(0.1mg/kg)灌胃组:对行DMM术构建膝关节骨关节炎模型后3天的小鼠予以SGLT2i(0.1mg/kg)灌胃处理,每天1次;
4)SGLT2i(1mg/kg)灌胃组:对行DMM术构建膝关节骨关节炎模型后3天的小鼠予以SGLT2i(1mg/kg)灌胃处理,每天1次;
5)SGLT2i(10mg/kg)灌胃组:对行DMM术构建膝关节骨关节炎模型后3天的小鼠予以SGLT2i(10mg/kg)灌胃处理,每天1次。
术后12周处死小鼠,切取小鼠的膝关节标本进行后续检测。
2.2、将60只SD大鼠随机分成5组,每组12只,具体分组情况如下:
1)假手术组:仅进行假手术处理;
2)生理盐水灌胃组:对行MIA注射构建膝关节骨关节炎模型后3天的大鼠予以生理盐水(1μL/g)灌胃处理,每天1次;
3)SGLT2i(0.1mg/kg)灌胃组:对行MIA注射构建膝关节骨关节炎模型后3天的大鼠予以SGLT2i(0.1mg/kg)灌胃处理,每天1次;
4)SGLT2i(1mg/kg)灌胃组:对行MIA注射构建膝关节骨关节炎模型后3天的大鼠予以SGLT2i(1mg/kg)灌胃处理,每天1次;
5)SGLT2i(10mg/kg)灌胃组:对行MIA注射构建膝关节骨关节炎模型后3天的大鼠予以SGLT2i(10mg/kg)灌胃处理,每天1次。
术后4周处死大鼠,切取大鼠的膝关节标本进行后续检测。
实施例3:疼痛行为学检测
对行MIA注射当天至注射后28天的大鼠每周进行1次疼痛阈值和双后肢负重差值进行检测,以评估疼痛相关行为。
1、疼痛阈值检测
采用von Frey测痛仪(IITC,Woodland Hills,CA,USA)测定大鼠的机械痛觉阈值:
将大鼠置于干净的底部为铁丝网空格有机玻璃箱内,适应环境15分钟(以大鼠在笼中觅食、打闹等活动停止为准);采用Von Frey纤维毛针(Semmes-Weinsteinmonofilaments)刺激大鼠右后肢足底中部;初始力度为0g,然后均匀加大刺激力度,若大鼠出现抬足、舔足或躲避等行为视为阳性反应,否则视为阴性反应;记录能够引起大鼠缩足反射的最小刺激力度,即为机械缩足反射阈值(机械痛觉阈值);连续测定5次,每次间隔3分钟,取其平均值。
2、双后肢负重差值检测
采用后肢负重测量仪(IITC,Woodland Hills,CA,USA)测定大鼠的双后肢负重差值:
将大鼠放入后肢负重测量仪中,待其安静后使其双后肢分别置于不同感应器上;保持3秒后,记录测量仪上双侧后肢分别显示的负重值(g);并重复测量3次,取平均值。
实施例4:膝关节组织的固定与石蜡切片的制备
I)剥去小鼠和大鼠完整的右后肢膝关节组织,置于4%多聚甲醛水溶液中,并于4℃摇床上固定20小时;
II)采用聚丁二酸丁二醇酯(PBS)冲洗固定后的组织2次,每次5分钟;
III)将冲洗后的组织置于15%乙二胺四乙酸水溶液(脱钙液)中进行脱钙处理,每7天更换一次脱钙液,小鼠膝关节组织脱钙处理7天,大鼠膝关节组织脱钙处理30天;
IV)对脱钙处理后的组织进行梯度乙醇脱水,具体程序依次为:50%乙醇水溶液,2小时;70%乙醇水溶液,2小时;80%乙醇水溶液,2小时;95%乙醇水溶液,2小时;100%乙醇I,过夜;100%乙醇II,2小时;
V)对乙醇脱水后的组织进行透明,即采用二甲苯置换乙醇,具体程序依次为:二甲苯I,30分钟;二甲苯II,30分钟;
VI)对透明后的组织进行浸蜡,即采用石蜡置换二甲苯,具体程序依次为:石蜡I,65℃处理1小时;石蜡II,65℃处理1小时;石蜡III,65℃处理1小时,随后冷却至室温(25±5℃);
VII)对浸蜡后的组织采用石蜡包埋机进行包埋,包埋时需保证蜡块完整无裂痕;然后采用石蜡切片机对包埋后的组织进行切片,切片厚度为5μm。
实施例5:病理学检测
从开始出现软骨面至软骨面消失中每隔10μm选择一张切片进行染色评分,每个膝关节选择5个连续切片进行以下操作:
I)将膝关节组织的石蜡切片置于65℃恒温箱中烘烤2小时后,将石蜡切片置于脱蜡液(牌号YA0031,购自Solaribo公司)进行脱蜡处理,共2次,每次浸泡20分钟;
II)对脱蜡处理后的组织进行梯度乙醇水合并清洗,具体程序依次为:100%乙醇水溶液,3分钟;90%乙醇水溶液,3分钟;80%乙醇水溶液,3分钟;70%乙醇水溶液,3分钟;50%乙醇水溶液,3分钟;然后采用PBS水溶液冲洗3分钟;
III)将冲洗后的组织切片分别进行番红固绿(购自Sigma Aldrich公司)染色、苏木精-伊红(HE,购自Sigma Aldrich公司)染色,具体地为:
1)番红固绿(Safranin O-fast green)染色以评估软骨退变:将冲洗后的组织切片置于固绿染液中浸泡3分钟后用去离子水洗去多余染液,然后置于1%冰醋酸水溶液分化5秒,去离子水冲洗;接着置于番红染液中浸泡30秒后进行梯度乙醇快速脱水,具体程序为:70%乙醇水溶液,5秒;80%乙醇水溶液,5秒;95%乙醇水溶液,5秒;100%乙醇,5秒;最后置于二甲苯中浸泡5分钟;最后将切片边缘多余的二甲苯拭去,快速滴加2滴中性树胶,再用盖玻片封片;
2)HE染色以评估滑膜炎:将冲洗后的组织切片置于苏木素染料中浸泡3分钟后用自来水洗去多余染液;接着置于分化液中分化30秒后用自来水浸泡15分钟;然后置于伊红染料中浸泡30秒后用自来水洗去多余染液,再用去离子水浸泡2分钟后进行梯度乙醇快速脱水,具体程序为:70%乙醇水溶液,5秒;80%乙醇水溶液,5秒;95%乙醇水溶液,5秒;100%乙醇,5秒;最后置于二甲苯中浸泡5分钟;最后将切片边缘多余的二甲苯拭去,快速滴加2滴中性树胶,再用盖玻片封片;
IV)对染色后的组织(仅小鼠)进行软骨破坏评分,具体地为:由两名评分人员在盲法条件下使用国际骨关节炎研究协会评分系统(OARSI,0-6级)对番红固绿染色切片进行软骨破坏评分,如有任何分歧,则加入第三名评分人员,并通过讨论后以少数服从多数原则解决分歧;
用同样的方法使用滑膜衬里层及细胞密度评分系统(0-6级)对苏木精-伊红染色切片进行滑膜炎评分(仅大鼠)。
实施例6:免疫组化分析
I)将膝关节组织的石蜡切片置于65℃恒温箱中烘烤2h后,将石蜡切片置于脱蜡液(牌号YA0031,购自Solaribo公司)中进行脱蜡处理15分钟;
II)对脱蜡处理后的组织进行梯度乙醇水合并清洗,具体程序依次为:100%乙醇水溶液,3分钟;90%乙醇水溶液,3分钟;80%乙醇水溶液,3分钟;70%乙醇水溶液,3分钟;50%乙醇水溶液,3分钟;然后采用PBS水溶液冲洗3分钟;
III)采用链霉亲和素生物素+辣根过氧化物酶试剂盒(牌号SP-9001,购自ZSGB-BIO公司)进行免疫组化染色,并用10%山羊血清水溶液于室温(25±5℃)条件下孵育30分钟以进行封闭;
IV)将封闭后的组织分别与以下抗体于4℃条件下孵育过夜:
MMP-13抗体(牌号18165-1-AP,购自Proteintech公司)、ADAMTS-5抗体(牌号ab41037,购自Abcam公司);
V)将与抗体孵育后的组织进行染色,具体地为:将3,3-二氨基联苯胺四盐酸盐(DAB,购自ZSGB-BIO公司)滴加于组织上,待显色结束后立即于去离子水中终止反应;并用去离子水冲洗5分钟后将组织于苏木素染液中染色30秒,并用去离子水冲洗10分钟后于显微镜下进行观察。
实验结果
本发明中所有数据均以均值±标准差表示。数据分析采用软件SAS9.4进行分析,使用单向方差分析或双向重复方差分析的统计学方法进行分析,其中,时间和组间的相互效应采用双向重复方差分析来评估,所有P值均为双侧P值,统计学差异的阈值是P<0.05。
表1:基线的基本信息
注:n表示样本数量。
图1为SGLT2i组与其他降糖药物组中髋或膝关节置换手术累积发生率曲线图。从图中可以看出,服用SGLT2i的人群发生髋或膝关节置换手术的风险低于服用其他降糖药物的人群。表明SGLT2i对OA的发生和进展均具有保护作用,可用于OA的预防和治疗,能够降低OA患者关节置换的风险。
图2为不同干预处理后小鼠膝关节软骨退变情况图,图3为不同干预处理后小鼠膝关节软骨中股骨和胫骨的OARSI评分结果图。从图2和图3中可以看出,生理盐水灌胃组的小鼠在术后12周表现出明显的软骨退变,OARSI评分高于假手术组,中低浓度的SGLT2i灌胃(0.1mg/kg和1mg/kg)能够轻微减轻DMM手术造成的膝关节软骨退变,但评分与生理盐水灌胃组相比无统计学差异,高浓度的SGLT2i灌胃(10mg/kg)能够显著减轻DMM手术造成的膝关节软骨退变。
图4为不同干预处理后小鼠膝关节软骨中MMP13和ADAMTS-5免疫组化染色情况图,图5为不同干预处理后小鼠膝关节软骨中MMP13和ADAMTS-5的定量结果图。从图4和图5中可以看出,生理盐水灌胃组的小鼠术后12周的膝关节软骨细胞中MMP13和ADAMTS-5的表达显著增加,中低浓度的SGLT2i灌胃(0.1mg/kg和1mg/kg)能够轻微减轻MMP13和ADAMTS-5的表达上调,但与生理盐水灌胃组相比,结果无统计学意义,而高浓度的SGLT2i灌胃(10mg/kg)能够显著降低MMP13和ADAMTS-5的表达。
图2-图5的结果表明,SGLT2i能够延缓DMM诱导的小鼠OA模型的软骨退变进展。
图6为不同干预处理后大鼠疼痛行为学结果图。从图中可以看出,生理盐水灌胃组大鼠在术后4周表现出明显的疼痛阈值下降和双足负重差异,中低浓度的SGLT2i灌胃(0.1mg/kg和1mg/kg)无明显治疗效果,而高浓度的SGLT2i灌胃(10mg/kg)能够显著减轻MIA注射造成的疼痛行为学改变。
图7为不同干预处理后大鼠膝关节滑膜HE染色情况图,图8为不同干预处理后大鼠膝关节滑膜炎评分结果图。从图7和图8中可以看出,与假手术组相比,生理盐水组的大鼠滑膜增生和炎性细胞浸润明显增加,仅高浓度的SGLT2i灌胃(10mg/kg)能够显著减轻MIA注射造成的膝关节滑膜炎症。
以上结果表明SGLT2i能够减轻MIA诱导的大鼠OA模型的疼痛行为学改变,抑制膝关节滑膜炎,延缓OA发生发展。
以上详细描述了本发明的优选实施方式,但是,本发明并不限于此。在本发明的技术构思范围内,可以对本发明的技术方案进行多种简单变型,包括各个技术特征以任何其它的合适方式进行组合,这些简单变型和组合同样应当视为本发明所公开的内容,均属于本发明的保护范围。
Claims (2)
1.达格列净在制备预防和治疗骨关节炎的药物中的应用,其特征在于,该药物为具有保护软骨细胞的功能、保护软骨的功能、缓解由骨关节炎引起的软骨退变的功能、减轻由骨关节炎引起的疼痛症状的功能、抑制由骨关节炎引起的滑膜炎的功能、降低骨关节炎患者关节置换的风险的功能中的至少一种功能的药物。
2.根据权利要求1所述的应用,其中,所述骨关节炎选自膝关节关节炎、髋关节关节炎、踝关节关节炎、肩关节关节炎、肘关节关节炎和手关节关节炎中的至少一种。
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