CN108882744A - 含有益智提取物作为有效成分的用于预防、改善或治疗高尿酸血症或与高尿酸血症相关的代谢障碍的组合物 - Google Patents
含有益智提取物作为有效成分的用于预防、改善或治疗高尿酸血症或与高尿酸血症相关的代谢障碍的组合物 Download PDFInfo
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Abstract
本发明涉及含有益智提取物作为有效成分的用于预防、改善或治疗高尿酸血症或与高尿酸血症相关的代谢障碍的组合物,本发明的益智提取物具有降低动物模型的血清中的尿酸的效果,并且是源自天然物质的有效成分,因此不仅安全,而且原料的供应也比较容易,从而能够广泛应用于高尿酸血症或与高尿酸血症相关的代谢障碍的相关产业。尤其,能够有效地用于预防、改善或治疗痛风或痛风性关节炎。
Description
技术领域
本发明涉及含有益智提取物作为有效成分的用于预防、改善或治疗高尿酸血症或与高尿酸血症相关的代谢障碍的组合物。
背景技术
高尿酸血症是根据男性超过6.8~7.0mg/dL或女性超过6mg/dL的血液中的尿酸值来定义的。美国的高尿酸血症及与高尿酸血症相关的代谢障碍(例如,痛风)的发病人数为3百万名至5百万名。在美国,非洲裔美国人患痛风的可能性是白人的2倍。此外,痛风及高尿酸血症正在中国、日本、波利尼西亚及撒哈拉城市以南的非洲蔓延,1990年至2010年之间的痛风的发病率大约变为2倍,并且韩国的痛风患者人数呈平均每年增加14%左右的趋势。
与高尿酸血症相关的代谢障碍不仅包括痛风,而且还包括尿酸结晶、关节内尿酸盐结晶的沉积、肾实质内尿酸盐结晶的沉积所导致的急性、单关节性、炎症性关节炎的痛症发作、尿路结石、肾结石及痛风性肾病。众所周知长期的肾结石及痛风性肾病会增加肾脏的损伤及肾衰竭的危险。与高尿酸血症相关的代谢障碍中的痛风是随着血液中的尿酸(人体对通过饮食而摄入的被称为嘌呤的物质进行代谢后剩下的产物)浓度的升高,尿酸盐(在血液、体液、关节液中,尿酸以尿酸盐的形态存在)结晶沉积在关节的软骨、腱、周边组织中的疾病。这种现象会诱发关节的炎症,从而引发伴有剧烈疼痛的复发性发作,并且随着由尿酸盐结晶导致的痛风结节(tophi)的沉积,会发生关节的变形和残疾。除了关节的异常,还会引发多种肾脏疾病,并且还会出现由尿酸导致的肾脏中形成石头的肾石病(nephrolithiaisis)。
此外,痛风是经过无症状高尿酸血症、急性痛风性关节炎、间歇性痛风、慢性结节性痛风等阶段而出现。初期出现的无症状高尿酸血症为血清中的尿酸的浓度会增加,但是尚未出现关节炎症状、痛风结节、尿酸肾石病等症状的状态。急性痛风性关节炎是在经过大体上至少持续20年的高尿酸血症后出现痛风发作或发生肾石病的阶段,最具特征的症状为非常痛苦的关节炎的急性发作,虽然初期侵入一个关节且没有全身的症状,但是会渐渐侵入多个关节,并伴有发热。间歇性痛风是指痛风发作之间没有症状的期间,大部分情况下,在第一次发作后的6个月到2年内会经历第二次发作,虽然根据治疗而不同,但频率会逐渐增加,并且侵入多个关节。就慢性结节性痛风而言,经过没有痛风的间歇期后进入慢性结节性痛风时期时,看起来会与其他种类的关节炎相似。侵入部位的关节会发生渐进性的僵硬和持续性的痛症。
已知痛风是其治疗方法明确且可以成功得到治疗的疾病,但是伴有高血压、慢性肾衰竭等其他疾病的情况很常见,因此多数情况下需要细心考虑药剂的副作用,并且作为非药物性治疗,患者努力改变生活习惯对于长期治疗的良好的预后是必需的。虽然痛风和高尿酸血症不属于代谢综合征的诊断标准,但认为其与代谢综合征具有密切的关系,其中,所述代谢综合征是显示出高血压、高脂血症、血糖增加、腹部肥胖等临床表现且导致动脉硬化性心脏疾病和2型糖尿病等成人疾病的风险度增加的复合型病症。据报道44%的韩国的痛风患者伴有代谢综合征。痛风一般以急性单关节炎的形态出现,但也会侵入少数关节或者罕有地侵入多关节。众所周知,用于治疗急性痛风的非甾体类抗炎药(non-steroidalanti-inflammatory drugs;NSAIDs)抑制炎症反应,通过抑制白细胞的活性及移动而显示出抗炎症作用的秋水仙碱(colchicine)、类固醇均是能够有效地治疗痛风发作的药剂,并且已知选择性环氧化酶(cyclooxygenase;COX-2)抑制剂也具有与现有的非甾体类抗炎药相同的效果。
此外,将血液中的尿酸浓度长时间维持在饱和状态以下时,不仅能够预防急性痛风性关节炎,而且还能够减小已经形成的痛风结节(tophi)的大小。在痛风慢性期会进行降低血液中的尿酸浓度的治疗,尿酸降低剂根据机制大致分为黄嘌呤氧化酶(xanthineoxidase;XO)抑制剂和促尿酸排泄剂(uricosuric agent),尿酸合成抑制剂有传统的广泛使用的别嘌呤醇(allopurinol)和最近开发的新药非布索坦(febuxostat)。别嘌呤醇(allopurinol)是黄嘌呤氧化酶(xanthine oxidase;XO)抑制剂,其是不用考虑高尿酸血症的原因而可以有效地进行使用的药物,但是已知别嘌呤醇(allopurinol)的最严重的副作用是超敏反应综合征(hypersensitivity syndrome),会出现发热、红斑、嗜酸性粒细胞增多、肝炎、肾衰竭等,并且具有导致死亡的危险。非布索坦(febuxostat)也是黄嘌呤氧化酶抑制剂,但与别嘌呤醇(allopurinol)不同,其为非嘌呤类选择性阻断剂,主要在肝中代谢而形成葡糖苷酸(glucuronide)。大部分的痛风是以慢性发展,这时即使没有症状,也会预防性地进行抗炎症制剂和降低尿酸浓度的治疗。这种预防治疗需要在疾病维持一定时间的镇静状态后进行,否则会复发更严重的痛风。但是,对于适当的疾病的镇静时期尚且存在诸多争议,此外,目前的情况是这种预防治疗也难以以目前开发的药剂来抑制间歇性复发的痛风的急性发病,并且通过利用天然物质来抑制作为诱发痛风(gout)的酶的氧化酶的技术尚不完善。
另外,益智(Alpiniae Fructus)为姜科(Zingiberaceae)的果实,生长于中国广东省和海南岛。益智的性状为两端呈稍尖的球形或椭圆形,长为1~2cm,直径为7~10mm。外表面为棕色至暗棕色,具有多个纵向连接的小凸起物形状的隆起线。果皮的厚度为0.3~0.5mm,并且与种子块粘附在一起,因此难以剥离。内部是以薄膜纵向分为3个格室,每个格室有5~8颗通过假种皮相互粘在一起的种子。种子为棕色至暗棕色,呈不规则的多面体,直径为约3.5mm,质地坚硬。有特殊的气味,味道微苦。已知益智含有以下成分:圆柚酮(nootkatone)、表圆柚醇(epinootkatol)、β-圆柚醇(β-nootkatol)、β-蒎烯(β-pinene)、对伞花烃(p-cymene)、4-萜烯醇(terpinen-4-ol)、作为二芳基庚烷类(diarylheptanoid)化合物的益智酮(yakuchinone)A和B,并且含有作为类黄酮成分的杨芽黄素(tectochrysin)、白杨素(chrysin)、良姜素(izalpinin)、3,5-二羟基-7,4'-二甲氧基黄酮(3,5-dihydroxy-7,4'-dimethoxyflavone)等。所述圆柚酮(nootkatone)具有抗胃溃疡的作用,所述益智酮(yakuchinone)A和B具有抗炎症作用,并抑制皮肤癌的产生,而且降低COX-2和iNOS的表达和NFκB的活性。此外,已知益智酮(yakuchinone)A、圆柚酮(nootkatone)及表圆柚醇(epinootkatol)具有杀虫效果,并已知其显示出保护脑细胞的作用、抗过敏作用、美白作用等。
此外,已知益智的精油成分增加药物的皮肤渗透力,并且通过竞争性地抑制钙离子进入细胞而显示出松弛平滑肌和抑制心肌的作用,而且起到抗利尿作用、抗溃疡作用、抗痴呆作用、改善学习能力的作用。
就与益智提取物或高尿酸血症相关的技术而言,韩国授权专利第1567885号公开了治疗高尿酸血症和与高尿酸血症相关的代谢性病症的方法和组合物,韩国公开专利第2006-0120791号公开了包含益智仁提取物的用于改善脂质代谢和预防及治疗肥胖的药学组合物,韩国公开专利第1992-0011502号公开了能够治疗人体神经系统的痛症的改良的附子理中汤中药治疗剂物质。
但是没有公开本发明的含有益智提取物作为有效成分的用于预防、改善或治疗高尿酸血症或与高尿酸血症相关的代谢障碍的组合物。
发明内容
要解决的技术问题
本发明是根据如上所述的需求而提出的,本发明提供含有益智提取物作为有效成分的用于预防、改善或治疗高尿酸血症或与高尿酸血症相关的代谢障碍的组合物,并通过确认本发明的有效成分益智提取物减少动物模型的血清中的尿酸,从而完成了本发明。
技术方案
为了实现所述目的,本发明提供用于预防或改善高尿酸血症或与高尿酸血症相关的代谢障碍的健康功能食品,其含有益智提取物作为有效成分。
此外,本发明提供用于预防或治疗高尿酸血症或与高尿酸血症相关的代谢障碍的药学组合物,其含有益智提取物作为有效成分。
发明效果
本发明涉及含有益智提取物作为有效成分的用于预防、改善或治疗高尿酸血症或与高尿酸血症相关的代谢障碍的组合物,其降低血清中的尿酸量,并且是源自天然的物质,因此安全,而且原料的供应容易,从而能够广泛应用于高尿酸血症或与高尿酸血症相关的代谢障碍的相关产业。尤其,能够有效地用于预防、改善或治疗痛风或痛风性关节炎。
附图说明
图1为对正常SD-大鼠动物模型施用本发明的益智提取物后确认血清中的尿酸量减少的结果。正常组表示正常动物模型组,益智200mg/kg表示对正常动物模型施用200mg/kg的益智提取物的动物模型组。
图2为对诱发高尿酸血症的SD-大鼠动物模型施用本发明的益智提取物后确认血清中的尿酸量减少的结果。正常组表示正常动物模型组,对照组表示通过施用氧嗪酸钾(Potassium Oxonate)来诱导高尿酸血症的动物模型组。
图3为在通过单钠尿酸盐(monosodium urate,MSU)诱导痛风性关节炎的C57/BL6小鼠中确认体重负荷率(%)的结果。正常组为阴性对照组,其是没有诱发痛风性关节炎的正常组,MSU为通过施用MSU来诱发痛风性关节炎的组,秋水仙碱为阳性对照组。#表示与正常组相比,通过施用MSU来诱发痛风性关节炎的组的体重负荷率(%)的减少具有统计学意义,表示p<0.05。*表示与诱导痛风性关节炎的MSU组相比,本发明的益智提取物处理组的体重负荷率(%)的增加具有统计学意义,*表示p<0.05。
图4为在通过单钠尿酸盐(monosodium urate,MSU)诱导痛风性关节炎的C57/BL6小鼠中确认减少IL-1β的效果的结果。正常组为阴性对照组,其是没有诱发痛风性关节炎的正常组,MSU为通过施用MSU来诱发痛风性关节炎的组,秋水仙碱为阳性对照组。#表示与正常组相比,通过施用MSU来诱发痛风性关节炎的组的IL-1β含量的增加具有统计学意义,表示p<0.0001。*表示与诱导痛风性关节炎的MSU组相比,本发明的益智提取物处理组的IL-1β含量的减少具有统计学意义,*表示p<0.05。
具体实施方式
本发明涉及用于预防或改善高尿酸血症或与高尿酸血症相关的代谢障碍的健康功能食品,其含有益智提取物作为有效成分。
所述与高尿酸血症相关的代谢障碍优选为选自急性或慢性痛风、痛风性红肿、痛风性关节炎、痛风性肾结石及痛风性肾病中的任一种,但并不限定于此。所述痛风性红肿是指由痛风引起的炎症等导致发红的症状。
所述益智提取物优选使用C1~C4的低级醇、水或它们的混合物作为溶剂进行提取,更优选使用乙醇作为溶剂进行提取,进一步优选使用70%(v/v)的乙醇作为溶剂进行提取,但并不限定于此。
所述含有益智提取物作为有效成分的用于预防或改善高尿酸血症或与高尿酸血症相关的代谢障碍的健康功能食品可以制备为选自饮料、丸、片剂(tablet)、胶囊剂(capsule)、散剂中的任一种,或者可以添加到其他食品或食品的成分中来制备,并且可以根据常规的方法适当地进行制备。
可以添加本发明的益智提取物的食品的一个例子可以是选自肉类、香肠、面包、巧克力、糖果类、点心类、饼干类、比萨、方便面、其他面类、口香糖类、包括冰淇淋类的乳制品、各种汤、饮料、茶、保健饮料、酒精饮料及维生素复合剂中的任一种形态,并且包括所有常规意义上的健康食品。
所述健康功能食品可以含有多种营养剂、维生素、矿物(电解质)、合成及天然风味剂、着色剂及增强剂(奶酪、巧克力等)、果胶酸及其盐、海藻酸及其盐、有机酸、保护性胶体增稠剂、pH调节剂、稳定化剂、防腐剂、甘油、酒精、碳酸饮料中使用的碳酸化剂等。此外还可以含有用于制备天然果汁及蔬菜饮料的果肉。这些成分可以单独使用或组合使用。
本发明的健康功能食品可以含有多种香味剂或天然碳水化合物等作为附加成分。所述天然碳水化合物为诸如葡萄糖、果糖的单糖,诸如麦芽糖、蔗糖的二糖,以及诸如糊精、环糊精的多糖,木糖醇、山梨糖醇、赤藓糖醇等糖醇。甜味剂可以使用诸如奇异果甜蛋白、甜菊提取物的天然甜味剂,或者诸如糖精、阿斯巴甜的合成甜味剂等。
此外,本发明涉及用于预防或治疗高尿酸血症或与高尿酸血症相关的代谢障碍的药学组合物,其含有益智提取物作为有效成分。
所述药学组合物中,与高尿酸血症相关的代谢障碍优选为选自急性或慢性痛风、痛风性红肿、痛风性关节炎、痛风性肾结石及痛风性肾病中的任一种,但并不限定于此。所述痛风性红肿是指由痛风引起的炎症等导致发红的症状。
除了所述有效成分以外,可以进一步包含尿酸盐降低剂,优选的尿酸盐降低剂为选自黄嘌呤氧化酶抑制剂、促尿酸排泄剂(uricosuric agent)、尿酸盐氧化酶、尿碱化剂及非诺贝特中的一种以上,但并不限定于此,并且除了所述益智提取物以外,还可以进一步包含药剂学上可接受的载体、赋形剂或稀释剂。
本发明的药学组合物可以是口服或非口服的多种剂型。在进行制剂化时使用通常使用的填充剂、增量剂、粘合剂、润湿剂、崩解剂、表面活性剂等稀释剂或赋形剂来制备。用于口服施用的固体制剂包括片剂、丸剂、散剂、颗粒剂、胶囊剂等,这种固体制剂是通过在一种以上的化合物中混合至少一种以上的如淀粉、碳酸钙、蔗糖(sucrose)或乳糖(lactose)、明胶等赋形剂来制备。此外,除了单纯的赋形剂以外,还使用如硬脂酸镁、滑石等润滑剂。用于口服施用的液体制剂有悬浮剂、内用液剂、乳剂、糖浆剂等,除了常用的单纯稀释剂的水、液体石蜡以外,可以包含多种例如润湿剂、甜味剂、芳香剂、保存剂等的赋形剂。用于非口服施用的制剂包括灭菌的水溶液、非水性溶剂、悬浮剂、乳剂、冷冻干燥制剂、栓剂。非水性溶剂及悬浮溶剂可以使用丙二醇(propylene glycol)、聚乙二醇、诸如橄榄油的植物油、诸如油酸乙酯的可注射的酯等。栓剂的基质可以使用witepsol、聚乙二醇(Macrogol)、吐温(tween)61、可可脂、月桂脂、甘油明胶等。
本发明的组合物可以通过口服或非口服进行施用,非口服施用时优选选择皮肤外用或腹腔内、直肠、静脉、肌肉、皮下、子宫内硬膜或脑血管内注射的方式,最优选以皮肤外用进行使用。
本发明的组合物是以药剂学有效量进行施用。本发明中,“药剂学有效量”是指可应用于医学治疗并以合理的受益/风险比例治疗疾病所充足的量,有效剂量的水平可以根据包括患者的疾病的种类、严重程度、药物的活性、对药物的敏感度、施用时间、施用途径及排泄比率、治疗疗程、同时使用的药物在内的因素及其他医学领域中众所周知的因素来决定。本发明的组合物可以作为单独的治疗剂来进行施用或可以与其他治疗剂联合施用,可以依次或同时与现有的治疗剂进行施用,并且可以进行单一或多种施用。重要的是考虑所有上述因素,并在没有副作用的情况下,施用能够以最少的量获得最大效果的量,这可以由本领域技术人员容易地决定。
本发明的组合物的施用量的范围可以根据患者的体重、年龄、性别、健康状态、饮食、施用时间、施用方法、排泄率及疾病的严重程度而不同。
下面,通过实施例对本发明进行更加详细的说明。这些实施例仅仅是用于更加具体地说明本发明,而本发明的范围不受其限制,这对于本领域具有通常知识的技术人员而言是显而易见的。
实施例1.益智提取物的制备
向1kg的益智添加15L的70%(v/v)的乙醇,并在85℃下进行回流提取3小时,然后将过滤的液体在50℃下进行减压浓缩,并进行干燥,从而获得11.7g的益智提取物。
实施例2.确认正常SD-大鼠动物模型的血液中包含的尿酸的减少
将200mg/kg的益智提取物和作为阳性对照组的50mg/kg的别瞟呤醇分别悬浮于包含0.1%的聚氧乙烯脱水山梨醇单油酸酯(polyoxyethylene sorbitan monooleate)的0.01M的PBS(磷酸盐缓冲溶液(phosphate buffered saline))缓冲溶液中,并对正常动物模型的SD-大鼠进行口服施用1次。
口服施用后的2小时之后,用乙醚(ethyl ether)进行麻醉,然后采集血液,并使用尿酸测定试剂盒(ab65344,艾博抗(abcam)公司,美国)测量尿酸的量。
血液中的尿酸量的测量结果如图1所示,由于施用益智提取物而使尿酸量减少,显示出约2.1ml/dl,与正常组相比,确认了26%的血液中的尿酸得到减少。
实施例3.分析在诱发高尿酸血症的动物模型的血液中包含的尿酸的减少效果
为了在高尿酸血症诱发动物模型的SD-大鼠中诱发高尿酸血症,将溶解于包含0.1M的乙酸钠(sodium acetate)的0.5%的羧甲基纤维素钠(SodiumCarboxymethylcellulose;CMC-Na,pH为5.0)溶液中的150mg/kg的氧嗪酸钾(PotassiumOxonate)进行腹腔注射。
24小时后采集尿液,并使用尿酸测定试剂盒(ab65344,艾博抗(abcam)公司,美国)筛选诱发高尿酸血症的动物模型。
将100mg/kg、200mg/kg及300mg/kg的益智提取物和作为阳性对照组的50mg/kg的别瞟呤醇悬浮于包含0.1%的聚氧乙烯脱水山梨醇单油酸酯(polyoxyethylene sorbitanmonooleate)的0.01M的PBS(磷酸盐缓冲溶液(phosphate buffered saline))缓冲溶液中,并对所述筛选的动物模型口服施用3天,并在尸检前一天绝食16小时。
在最后一次口服施用后的2小时之后,用乙醚(ethyl ether)进行麻醉,然后采集血液,并使用尿酸测定试剂盒(ab65344,艾博抗(abcam)公司,美国)测量尿酸的量。
尿酸量的测量结果如图2所示,由于施用氧嗪酸钾而引起尿酸量的增加,显示出约4.5ml/dl,并且对所述诱导高尿酸血症的动物模型分别以100mg/kg/天、200mg/kg/天及300mg/kg/天的量施用本发明的益智提取物的结果,确认了血清中的尿酸的量从约4.5ml/dl减少至约1.79、1.75及1.76ml/dl。即,具有如下效果:与高尿酸血症动物模型组相比,施用本发明的益智提取物的高尿酸血症动物模型的血液中的尿酸量减少约60~62%左右。
实施例4.评价通过单钠尿酸盐(Monosodium urate,MSU)诱导痛风性关节炎的动物模型中的益智提取物的功效
(1)体重负荷率(%)的测量
为了确认在上述实施例1中提取的益智提取物对痛风性关节炎的功效,在通过单钠尿酸盐(Monosodium urate,MSU)诱导痛风性关节炎疾病的动物模型中计算了体重负荷率(%)。
将融解于0.5%的CMC中的150mg/kg及300mg/kg的益智提取物口服施用于7周龄的C57/BL6小鼠。在施用所述益智提取物后的1小时后,将4mg的MSU悬浮于50μl的包含2.5%的吐温(tween)80的PBS中,并注射在右爪组织(paw tissue),从而诱导痛风性关节炎。以1天1次的频率施用药物4天后,在用MSU诱导的第5天进行尸检。使用秋水仙碱(colchicine)作为阳性对照组。
使用脚重量测量仪对后肢的体重负荷进行测量。诱发痛风性关节炎的小鼠由于痛症而会依赖没有施用MSU的正常爪子站立,因此两边爪子的重量会失去平衡,与正常爪子的重量相比,所测量的施用MSU的爪子的重量相对轻。利用所述测量的爪子的重量(g)计算体重负荷率(%)。所述体重负荷为用爪子支撑而向下压的力,正常情况下,两只爪子的体重分布比(weight distribution ratio,%)显示为50%,但是痛症越严重,体重分布比(%)越低。
体重负荷率(%)=(诱发关节炎的后肢的重量/正常后肢的重量+诱发关节炎的后肢的重量)×100
其结果,如图3所示,可以确认与正常组相比,MSU组的体重负荷率减少,施用本发明的益智提取物的组的体重负荷率浓度依赖性地得到恢复。
(2)IL-1β蛋白质表达量的确认
为了确认在上述实施例1中提取的益智提取物对痛风性关节炎的功效,对通过单钠尿酸盐(Monosodium urate,MSU)诱导痛风性关节炎疾病的动物模型中的IL-1β蛋白质的表达量进行分析。
将融解于0.5%的CMC的150mg/kg及300mg/kg的益智提取物口服施用于7周龄C57/BL6小鼠。在施用所述益智提取物后的1小时后,将4mg的MSU悬浮于50μl的包含2.5%的吐温(tween)80的PBS中,并注射在右爪组织(paw tissue),从而诱导痛风性关节炎。以1天1次的频率施用药物4天后,在用MSU诱导的第5天进行尸检。
之后,将在上述尸检中采集的爪组织(paw tissue)浸泡在RIPA缓冲溶液中并对组织进行破碎,通过ELISA法对上清液中的作为炎症指标的IL-1β蛋白质的表达量进行测量,并使用秋水仙碱(colchicine)作为阳性对照组。
其结果,如图4所示,确认了就因痛风性关节炎而增加的IL-1β而言,由于施用益智提取物,IL-1β显著地减少。
Claims (8)
1.用于预防或改善高尿酸血症或与高尿酸血症相关的代谢障碍的健康功能食品,其含有益智提取物作为有效成分。
2.根据权利要求1所述的用于预防或改善高尿酸血症或与高尿酸血症相关的代谢障碍的健康功能食品,其特征在于,所述与高尿酸血症相关的代谢障碍为选自急性或慢性痛风、痛风性红肿、痛风性关节炎、痛风性肾结石及痛风性肾病中的任一种。
3.根据权利要求1所述的用于预防或改善高尿酸血症或与高尿酸血症相关的代谢障碍的健康功能食品,其特征在于,所述益智提取物是使用C1~C4的低级醇、水或它们的混合物作为溶剂进行提取。
4.用于预防或治疗高尿酸血症或与高尿酸血症相关的代谢障碍的药学组合物,其含有益智提取物作为有效成分。
5.根据权利要求4所述的用于预防或治疗高尿酸血症或与高尿酸血症相关的代谢障碍的药学组合物,其特征在于,所述与高尿酸血症相关的代谢障碍为选自急性或慢性痛风、痛风性红肿、痛风性关节炎、痛风性肾结石及痛风性肾病中的任一种。
6.根据权利要求4所述的用于预防或治疗高尿酸血症或与高尿酸血症相关的代谢障碍的药学组合物,其中,除了所述有效成分以外,所述药学组合物进一步包含尿酸盐降低剂。
7.根据权利要求6所述的用于预防或治疗高尿酸血症或与高尿酸血症相关的代谢障碍的药学组合物,其特征在于,所述尿酸盐降低剂为选自黄嘌呤氧化酶抑制剂、促尿酸排泄剂(uricosuric agent)、尿酸盐氧化酶、尿碱化剂及非诺贝特中的一种以上。
8.根据权利要求4所述的用于预防或治疗高尿酸血症或与高尿酸血症相关的代谢障碍的药学组合物,其特征在于,除了所述益智提取物以外,所述药学组合物还进一步包含载体、赋形剂或稀释剂。
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WO2017176082A1 (ko) | 2017-10-12 |
KR20170115838A (ko) | 2017-10-18 |
KR101863604B1 (ko) | 2018-06-04 |
JP6762371B2 (ja) | 2020-09-30 |
JP2019513382A (ja) | 2019-05-30 |
US20190099465A1 (en) | 2019-04-04 |
US10709754B2 (en) | 2020-07-14 |
CN108882744B (zh) | 2022-04-19 |
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