CN1585646A - 用于治疗皮下软组织疼痛的锶化合物 - Google Patents
用于治疗皮下软组织疼痛的锶化合物 Download PDFInfo
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- CN1585646A CN1585646A CNA028222628A CN02822262A CN1585646A CN 1585646 A CN1585646 A CN 1585646A CN A028222628 A CNA028222628 A CN A028222628A CN 02822262 A CN02822262 A CN 02822262A CN 1585646 A CN1585646 A CN 1585646A
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- strontium
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- soft tissue
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Abstract
本发明提供一种治疗人类或非人类患者皮下软组织疼痛的方法，所述的方法包括给予所述的患者服用有效量的生理上可容忍的锶化合物。
Description
本发明涉及使用锶化合物治疗皮下软组织疼痛，特别是慢性疼痛的方法，本发明还涉及锶化合物在制备用于治疗皮下软组织疼痛，特别是慢性疼痛的药物中的用途以及新的含锶药物组合物。
疼痛是一种主观感受。根据International Association for the Study of Pain(IASP)，疼痛是一种与组织损伤有关的不舒服感觉和情绪上的感受。肌体本身有它自己的抑制机制，其使用脑啡肽和内啡肽来克制疼痛的刺激。肌体的其它机制，在某些情况下，起到增强疼痛的作用。因为疼痛是这样一种复杂的感受，因此一点也不惊讶，疼痛在人与人之间存在差异，或者对于相同的个体，疼痛可以随时间、地点和情况而改变。
通常，疼痛可以分为下面几种类型：
伤害性疼痛；
神经性疼痛；
心理性疼痛；和
突发性疼痛。
也可以将疼痛分为急性疼痛或慢性疼痛。慢性疼痛是指延续或复发超过6个月并且不能作针对原因治疗的疼痛。慢性疼痛患者可以定义为在一段时期内持续经历疼痛的个体，例如由于肌骨胳疾病、意外事故(例如运动损伤)、外科手术、软组织癌症(例如咽喉癌)、耻骨联合功能障碍、疤痕组织、或疾病或病症，例如风湿病造成的疼痛。
在全世界范围内，越来越需要这样的治疗以减少或消除慢性疼痛或急性疼痛。目前减轻疼痛的治疗常常包括药物治疗或神经破坏。然而，还需要开发一种缓减慢性疼痛和急性疼痛的方法，特别是皮下软组织疼痛，例如肌肉疼痛或腱疼痛，疤痕组织内或手术刀口位置的疼痛、关节疼痛、胸痛、背痛、粘液囊疼痛(例如与粘液囊炎有联系的疼痛)等等，特别是开发一种疼痛患者无需医疗救助就可以进行治疗的方法。
锶化合物用于治疗局部皮肤和粘膜以及牙齿的发痒或刺激是已知的。放射性锶化合物用于治疗与转移性骨癌有关的疼痛也是众所周知的(由于锶放射性核素发射的放射作用)。
然而，我们经探索研究意外地发现，锶化合物还可以用来有效地减少或消除皮下软组织疼痛。
因此，本发明的一个方面是提供一种治疗人类或非人类(例如脊椎动物，特别是哺乳动物)患者皮下软组织疼痛(例如肌肉、筋、腱或粘液囊疼痛，特别是肌肉疼痛)的方法，特别是慢性或急性疼痛，其中尤其是慢性疼痛，所述方法包括：给所述需要进行这样治疗的患者服用有效量的生理上可容忍的锶化合物。
本发明的另一方面是生理上可容忍的锶化合物在制备用于治疗皮下软组织疼痛，特别是慢性疼痛的药物中的用途。
本发明治疗的疼痛例如是与粘液囊炎、腱膜炎、风湿病、神经病、外科手术、创伤(例如运动创伤)、疤痕组织、可疑的心肌梗塞、背肌、软组织癌症、耻骨联合功能障碍和肌骨胳疾病有关的疼痛。但是，它一般不用来治疗头痛或胃痛，尽管如果需要，它也可以用来治疗头痛或胃痛。
本发明使用的锶化合物优选是非放射性的。在这里，″非放射性″是指锶化合物中放射性的锶同位素不那么丰富以致它可有资格作为用于医学目的的放射性材料使用。虽然存在于锶化合物中的极少比例的锶可以是放射性的，但是锶化合物中放射性的锶同位素含量通常至多为天然丰度的1000倍，优选至多是天然丰度的100倍，更优选至多是天然丰度的5倍。最优选的锶化合物包含的放射性锶同位素不大于它们的天然丰度。
本发明使用的锶化合物可以是能够作为锶离子源服用的任何生理上可容忍的锶化合物。通常，该化合物可以是无机盐或有机盐或者是一种络合物，例如与螯合剂形成的络合物。优选的化合物的例子包括氯化物、硝酸盐、硫酸盐、苹果酸盐、柠檬酸盐、乳酸盐、草酸盐、富马酸盐、酒石酸盐、丙二酸盐、乙酸盐、葡糖酸盐、戊烯二酸盐、对氨基马尿酸、琥珀酸盐、磷酸盐、磷酸氢盐、甘油磷酸盐、氨基己酸盐、苦杏仁酸盐、二苯甲酰基酒石酸盐、硬脂酸盐、抗坏血酸、苯甲酸盐、3，4-二甲氧基苯甲酸盐、和氨甲蝶呤、以及与青霉胺、酪氨酸、亮氨酸等等形成的络合物。如果以盐的形式存在，尤其优选是氯化物、硝酸盐、乙酸盐、柠檬酸盐、乳酸盐或磷酸氢盐形式的锶化合物，特别是氯化物、乙酸盐、柠檬酸盐、乳酸盐或磷酸氢盐形式的锶化合物，更特别是氯化物形式的锶化合物。
但是，锶化合物也可以以螯合物的形式存在，例如与多羧酸或多磷酸化合物或环状聚醚形成螯合物。
适当的螯合剂的例子是核医学和核磁共振成像领域所公知的(例如参见the scientific and patent literature from Amersham，Nycomed，Schering，Salutar，Bracco，Sterling Winthrop，Mallinckrodt等等)。可以使用线状或环状多齿螯合剂，例如EDTA、DTPA、EGTA、DTPA-BMA、DOTA、DO3A、1，2-二(氨基乙氧基)乙烷-N，N，N′，N′-四乙酸、Kryptofix 5和Kryptofix 222，EDTA是尤其特别优选的。
锶化合物尤其优选与其它止痛药，例如阿斯匹林、布洛芬、或其它NSAIDs或COX-2抑制剂、或者这样的止痛药的盐或络合物一起服用。
如果所需，锶化合物可以以具有酸性基团或胺基的药物化合物的盐或络合物的形式给予，这样的化合物优选具有有益于患者经受的疾病的生理作用，例如一种在治疗疼痛的根本病症上有效的化合物。在氨基药物的情况中，所得锶化合物通常是具有氨基药物作为反离子的锶螯合物。这种药物化合物的例子包括制霉菌素、5-氨基水杨酸、柳氮磺吡啶、偶氮水杨酸、谷氨酸、repaglinid、泛酸、依前列醇、依洛前列、替罗非班、凝血酸、叶酸、呋喃苯胺酸、布美他尼、kanrenoic acid、卡托普利(capopril)、依那普利、赖诺普利、雷米普利、福森普利、群多普利、缬沙坦、泰米沙坦、帕伐他丁、氟伐地汀、阿伐他汀、西立伐他汀、磺胺嘧啶、维甲酸、阿达帕林(adapalen)、壬二酸、地诺前列酮、甲四碘安(levotyroxin)、lityronin、多西环素、赖甲四环素、氧四环素、四环素、氨苄青霉素、羟氨苄青霉素、甲亚胺青霉素、青霉素G、苯氧甲基青霉素、双氯青霉素、氯青霉素、哌拉西林、克拉布兰酸、他巴克坦、头孢氨苄、先锋霉素I、头孢噻吩、头孢氨呋肟、头孢他定、头孢曲松、氨曲南、美罗匹宁、亚胺培南、西司他丁、环丙氟沙星、萘啶酸、褐霉酸、phoscarnet和扎那米韦。
在本发明中使用的各种锶化合物本身是新的，特别是锶与环加氧酶抑制剂(除了水杨酸盐(例如乙酰水杨酸)和昔康(例如吡罗昔康和替诺西康))、氨基酸、以及具有形成大于3个金属配位键，优选大于4个金属配位键的能力的多齿螯合剂(除了EDTA或EGTA)的盐或络合物。
合适的环加氧酶抑制剂的例子(例如COX1和/或COX2抑制剂)包括NSAIDs例如氨芬酸、苄达酸、丁苯羟酸、桂美辛、双氯芬酸、依托度酸、联苯乙酸、联苯丁酮酸、非诺洛芬、芬替酸、氟灭酸、氟苄烟酸、氟诺洛芬、氟比洛芬、呋洛芬、布洛芬、吲哚美辛、优洛芬、氯苯唑酸、环氧丙酸、甲灭酸、莫非佐酸、萘普生和尼氟灭酸。锶盐或锶络合物可以容易地通过碳酸锶与这些化合物的酸形式在溶液中进行反应在而制备。
因此，本发明的另一方面是提供一种锶和生理上可容忍的非水杨酸盐、非昔康环加氧酶抑制剂的盐或络合物。
本发明的另一方面是提供一种药物组合物，其包含锶和生理上可容忍的非水杨酸盐、非昔康环加氧酶抑制剂的盐或络合物连同一种药物载体或赋形剂。
可以用来形成本发明的锶化合物的氨基酸的例子包括所有天然α氨基酸，例如，酪氨酸、亮氨酸、赖氨酸等等。如同COX抑制剂一样，可以使用碳酸锶和氨基酸在溶液中制备化合物。但是，也可以使用其它锶盐，例如氯化物、乙酸酯和氢氧化物。
因此，本发明的另一方面是提供一种锶和α氨基酸的盐或络合物。
本发明的另一方面是提供一种药物组合物，其包含锶和α氨基酸的盐或络合物以及一种药物载体或赋形剂。
可用于制备本发明的新的锶化合物的螯合剂的例子包括在骨架氮原子上带有至少一个含氧酸(例如羧酸或磷酸)金属连接基的具有二亚乙基三胺或四氮杂环十二烷骨架的那些螯合剂，例如DTPA、DTPA-二甲酰胺、DOTA、D03A、羟丙基-D03A等等。这些螯合剂是诊断显象造影剂领域公知的，并且锶化合物再次可以容易地在溶液中由碳酸锶制备。
因此，本发明的另一方面是提供一种锶和生理上可容忍的二亚乙基三胺-或四氮杂环十二烷-骨架的螯合剂的盐或络合物。
本发明的另一方面是提供一种药物组合物，其包含锶和一种生理上可容忍的二亚乙基三胺-或四氮杂环十二烷-骨架的螯合剂的一种盐或络合物以及一种药物载体或赋形剂。
通常，以药物组合物的形式服用锶化合物，该药物组合物包含至少一种生理上可容忍的载体或赋形剂。在组合物中，锶化合物可以多达100％wt，优选在0.005-50％wt之间，更优选在0.05-20％wt之间，尤其是在0.1-10％wt之间，特别是在0.1-3％wt之间。可以使用常规的药物载体和赋形剂，例如溶剂(例如水、乙醇等等)、片剂、胶凝剂、防腐剂、乳化剂、氧化还原剂(例如抗氧化剂)、发泡剂、增稠剂、粘度调节剂、pH值调节剂等等。
在本发明的方法中使用的锶组合物可以根据现有给药方式采取任何方便的形式(例如口服、直肠、鼻、舌下、肌内、静脉内、阴道、经皮、局部或通过吸入)给药。因此，该组合物例如可以以溶液、分散液、悬浮液、凝胶剂、液晶体系和液晶前体、乳液、糖浆、片剂、糖衣片剂、胶囊、乳剂、糊剂、软膏、油膏剂、栓剂、喷雾剂、粉剂等等形式存在。对于静脉内和肌内给药，溶液是优选的。对于经皮或局部给药，溶液、乳剂、糊剂、软膏、乳液和凝胶剂是优选的。对于口服，溶液、糖浆、片剂、糖衣片剂和胶囊是优选的。
对于局部给药，该组合物尤其优选包含一种经皮渗透增强剂，包含这种渗透增强剂的锶组合物是新的，其构成本发明的另一方面。
因此，本发明的另一方面是提供一种减轻疼痛的局部药物组合物，包括一种生理上可容忍的锶化合物、一种生理上可容忍的载体(例如水溶剂、凝胶、浆状乳液或乳剂)和一种生理上可容忍的经皮渗透增强剂。
适宜的经皮渗透增强剂的例子包括月桂酸丙二醇酯、单月桂酸丙二醇酯、单辛酸丙二醇酯、十四烷酸异丙酯、月桂基硫酸钠、十二烷基吡啶鎓氯化物、油酸、丙二醇、二甘醇单乙醚、烟酸酯、氢化大豆磷脂、精油、醇(例如乙醇、异丙醇、正辛醇和癸醇)、萜烯、N-甲基-2-吡咯烷、α生育酚、聚丁二酸乙二醇酯(TPGS)、Tween 80、及其它表面活性剂、二甲基-β-环糊精和二甲基亚砜，尤其是二甲亚砜。
对于胃肠道或阴道给药，该组合物尤其优选包含生物粘合剂以促使组合物与粘膜之间更长的接触并且包含这种生物粘合剂的锶组合物是新的并构成本发明的另一方面。
因此，本发明的更进一步方面是提供一种减轻疼痛的药物组合物，包括一种生理上可容忍的锶化合物和一种生理上可容忍的生物粘合剂，任选连同一种生理上可容忍的载体或赋形剂。
本发明的生物粘合剂组合物优选包含以微粒化形式的锶化合物。
生物粘合剂(即粘膜粘着剂)以天然的或合成的、多阳离子、多阴离子或中性的，水溶性或不溶于水的形式存在，但是优选是大的(例如具有500-3000kDa.的分子量，例如1000-2000kda)、不溶于水的交联的(例如在任何水合之前，按聚合物总重量计算包含0.05-2％，例如0.75-1.5％交联剂)、水可膨胀的能够形式氢键的聚合物。根据Smart等人的方法J.Pharm.Pharmacol.36：p295-299(1984)进行估算，生物粘合剂优选具有大于100的粘膜粘着力，优选具有大于120的粘膜粘着力，特别是大于150的粘膜粘着力，相对于体外标准以百分比表示。
合适的生物粘合剂包括，但不限于，基于聚(含羧酸)的聚合物，例如具有强的氢连接基团的聚(丙烯、马来、衣康、柠康、羟乙基甲基丙烯或甲基丙烯)酸或其衍生物例如盐和酯。或者，可以使用纤维素衍生物例如甲基纤维素、乙基纤维素、甲基乙基纤维素、羟甲基纤维素、羟乙基乙基纤维素、羧甲基纤维素、羟丙基甲基纤维素或纤维素酯或醚或其衍生物或盐。也可以使用其它天然存在的或合成的聚合物如树胶，例如黄原胶、瓜尔胶、槐豆胶、黄蓍胶、梧桐胶、印度树胶、仙人掌胶、psillium seed gum和阿拉伯树胶；粘土如蒙脱土例如Veegum、山软木土；多糖如右旋糖酐、果胶、支链淀粉、琼脂、甘露聚糖或聚半乳糖酸或淀粉例如羟丙基淀粉或羧甲基淀粉；含多糖的亲脂性制剂，例如口腔膜剂基质(Bristol Myers Squibb)；碳水化合物，任选被基团例如硫酸酯、磷酸酯、磺酸酯或膦酸酯多取代，例如蔗糖八硫酸盐；多肽例如酪蛋白、谷蛋白、明胶、血纤维蛋白胶；壳聚糖(乳酸盐或谷氨酸盐)或羧甲基壳多糖；氨基多糖例如透明质酸；金属或褐藻酸的水溶性盐类例如海藻酸钠或褐藻酸镁；schleroglucan；含氧化铋或氧化铝的粘合剂；atherocollagen；聚乙烯聚合物例如聚乙烯醇、聚乙烯甲醚、聚乙烯吡咯烷酮、聚羧酸酯化的乙烯基聚合物(例如上述的聚丙烯酸)；聚硅氧烷；聚醚；聚环氧乙烷和聚乙二醇；聚烷氧化物和聚丙烯酰胺和其衍生物和盐。
还可以用生物粘合剂来与位于粘膜层下面的上皮细胞层结合。由于上皮细胞更新要比粘液更新相对较慢(天而不是小时)，这使得可以更特定的和更长久的持续粘合。因此，例如使用植物或细菌外源凝集素，即(glyco)非免疫性起源蛋白与多糖或缀合糖结合，其特异性地与上皮细胞膜的糖部分结合，可以获得受体调节相互作用。可以使用所谓的哺乳动物的″反转″外源凝集素，其中上皮细胞上的受体与加入的试剂的糖结合。来自细菌或病毒的其它生物粘合剂(例如粘合或侵入因素(例如细菌粘附素或与整联蛋白结合的透明质酸酶)通过仅仅与某些上皮细胞结合可以选择性地用于特定组织、表型、失调等等。
上述聚合的生物粘合剂还可以是交联的并且可以以共聚物的形式存在。优选可以使用高分子量的并且是触变的聚(丙烯酸)聚合物(或共聚物，例如与二或多官能的烯丙基醚或丙烯酸酯共聚以制备不溶的聚合物)，其优选是交联的，例如使用聚链烯基聚醚。具有这种形式的合适的生物粘合剂是可以从市场上买得到的(例如从Goodrich得到)聚卡波非，例如Noveon AA-1、卡波姆(卡波泊尔)，例如卡波泊尔EX165、EX214、434、910、934、934P、940、941、951、974P和1342。
因此，一些优选的生物粘合剂包括聚丙烯酸水凝胶、壳聚糖、聚乙烯醇、羟基丙基纤维素、羟丙基甲基纤维素、海藻酸钠、硬葡聚糖、黄原胶、果胶、口腔膜剂基质和聚半乳糖酸。
一种特别有效的经皮施用锶离子的方法是离子电渗疗法。含锶的离子电渗装置是新的并且构成本发明的另一方面。
因此，本发明的更进一步方面是提供一种离子电渗装置，其包括一个与药物贮存器电接触的阴极，其特征在于所述的药物贮存器包含一种生理上可容忍的锶化合物。
在本发明的离子电渗装置中，阴极优选是银电极并且锶化合物优选是氯化锶，这样的电极反应产生的是不溶的氯化银。药物贮存器优选包括一种含水凝胶，该含水凝胶包含以溶解形式的锶化合物。此外，该装置还优选包括一个不活泼的皮肤接触电极和一个电源如电池。
本发明人令人惊讶地发现，锶化合物，例如在此描述的类型，可以有效地抗击与疱疹感染有关的疼痛，特别是与带状疱疹(例如带状疱疹)和单纯性疱疹有关的疼痛。锶化合物可以局部施用，或者通过口服或注射的方法施用；但是优选局部施用。因此，本发明的另一方面是提供一种生理上可容忍的锶化合物在制备用于治疗疱疹感染的药物中的用途。本发明的另一方面是提供一种治疗具有疱疹感染症状的人或其它哺乳动物的方法，所述的方法包括给所述的患者服用一种有效量的生理上可容忍的锶化合物。
在下面的非限制实施例中进一步说明本发明。
实施例1
组合物
制备含锶组合物，如0.1％wt的氯化锶六水合物在水中的溶液。
实施例2
组合物
制备含锶组合物，如0.1％的氯化锶六水合物、0.1％wt的氯化镁六水合物和0.1％wt的氯化钙二水合物的水溶液。
实施例3
治疗
30个胸骨周围疼痛的患者被要求填写问卷调查表(VAS表格)以主观地指出胸骨周围疼痛的程度。此后，摸触胸骨并且填写VAS表格以指出疼痛的真实程度。在接受本发明的治疗之前，患者先进行肺活量测试(MVV)和温度记录法。
将患者分成三组，一组接受实施例1的组合物，第二组接受实施例2的组合物，第三组接受安慰剂组合物(水)。
在两个星期内，每天三次，由患者自己将该组合物用于患者的胸部(胸骨)。使液体在皮肤上干燥。
在治疗时期，患者每天填写VAS表格。再一个星期中，患者用浸有组合物的棉花垫均匀地擦拭他们的胸骨。将一些患者每周聚在一起进行检查和客观的进行VAS评价。治疗周期之后，患者再次进行MVV和温度记录法。
研究的结果是，接受锶组合物治疗的患者减轻了疼痛。疼痛治疗以前，VAS的平均值是7-8，而用锶治疗之后，VAS的平均值降低到1-2。安慰剂治疗显示无作用。
在另一种情况中，咽喉癌患者用0.1％wt的氯化锶溶液漱口，可以显著地减轻患者的疼痛。
实施例4
制备乙二胺四乙酸的锶(II)络合物(SrEDTA)
将锶(1.0g，6.77mmol)和乙二胺四乙酸(1.98g，6.77mmol)在水中(25ml)的悬浮液在70℃下搅拌30分钟。透明溶液蒸发至干，并在环境温度下在真空中进行干燥。分离得到白色晶体形式的标题化合物。产率2.79g(109％，以无水产物计算)。熔点超过250℃。
实施例5
亚乙基双(氧亚乙基次氮基)四乙酸的锶(II)络合物的制备(SrEGTA)
将碳酸锶(1.0g，6.77mmol)和亚乙基双(氧亚乙基次氮基)四乙酸(2.58g，6.77mmol)在水中(25ml)的悬浮液在70℃下搅拌6.5小时。溶液几乎变成澄清的。溶液在室温下过滤，滤液蒸发至干，并在环境温度下在真空中进行干燥。分离得到白色晶体形式的标题化合物。收率1.54g(49％)。
实施例6
制备锶(II)水杨酸盐
将碳酸锶(1.0g，6.77mmol)和水杨酸(1.87g，13.5mmol)在水中(25ml)的悬浮液搅拌4小时。溶液变成浅黄色并且几乎是澄清的。在室温下过滤溶液，滤液蒸发至干并在环境温度下在真空中进行干燥。分离获得浅红色粉末形式的标题化合物。收率2.1g(86％)。熔点超过300℃。
实施例7
制备二亚乙基三胺五乙酸的锶(II)络合物(SrDTPA)
将碳酸锶(1.0g，6.77mmol)和二亚乙基三胺五乙酸(2.67g，6.77mmol)在水中(25ml)的悬浮液在80℃下搅拌19小时。在室温下滤出不溶解的部分，滤液蒸发至干，并在环境温度下在真空中进行干燥。分离得到白色/浅黄色晶体形式的标题化合物。收率1.6g(49％)。M熔点约为250℃。还可以使用类似的方法，用乙酸锶代替碳酸锶，获得51％收率的标题化合物。
实施例8
制备L-抗坏血酸的锶(II)络合物
将碳酸锶(1.0g，6.77mmol)和L-抗坏血酸(2.39g，13.5mmol)在水中(25ml)的悬浮液在80℃下搅拌7小时。混合物变成黄色。混合物在室温下过滤，滤液蒸发至干，并在环境温度下在真空中进行干燥。分离获得黄色粉末形式的标题化合物。收率2.50g(78％)。熔点约为250℃。
实施例9
制备L-抗坏血酸6-棕榈酸酯的锶(II)络合物
将氯化锶六水合物(0.32g，1.2mmol)在水(3ml)中的溶液加入到在室温搅拌下的L-抗坏血酸6-棕榈酸酯(1.0g，2.4mmol)在乙醇/水(100ml，50∶50(体积))中的溶液中。混合物搅拌5分钟，过滤分离标题化合物，冷冻干燥。收率0.514g(47％)。白色粉末。
实施例10
制备锶布洛芬盐
将布洛芬(2.59g，12.5mmol)溶于含氢氧化钠(0.503g，12.5mmol)的水(100ml)中。向其中加入氯化锶六水合物(1.68g，6.3mmol)在水(5ml)中的溶液。混合物在室温下搅拌10分钟，过滤分离标题化合物并干燥。收率1.30g(44％)。熔点＞300℃。
实施例11
制备锶二氯芬酸盐
将二氯芬酸(0.35g，1.18mmol)溶解在含氢氧化钠(24mg，0.59mmol)的水/乙醇(30ml，50∶50(体积))中。混合物搅拌20分钟，过滤分离标题化合物并干燥。收率0.122g(15％)。
实施例12
预备硬脂酸锶
将硬脂酸(2.97g，10.4mmol)溶于含氢氧化钠(0.417g，10.4mmol)的水/乙醇(100ml，50∶50(体积))中。将混合物加热至70℃，向其中加入氯化锶六水合物(1.39g，5.2mmol)在水(3ml)中的溶液，离心形成的沉淀，分离获得标题化合物。收率1.6g(46％)。
实施例13
制备SrEDTA二甲葡胺(dimeglumine)盐
将锶EDTA(1g，2.65mmol)(从实施例4中获得)和N-甲基-D-葡糖胺(1.03g，529mmol)溶于水(10ml)中，并在70℃A下搅拌30分钟。混合物过滤，滤液蒸发至干，并在环境温度下在真空中进行干燥。分离得到白色晶体形式的标题化合物。收率0.722g(36％)。
实施例14
制备苯甲酸锶
将碳酸锶(1.0g，6.77mmol)和苯甲酸(1.65g，13.5mmol)在水中(30ml)的悬浮液在70℃下搅拌4小时。过滤混合物，滤液蒸发至干，并在环境温度下在真空中进行干燥。分离得到标题化合物。收率1.8g(81％)。
实施例15
制备戊二酸锶
将碳酸锶(1.0g，6.77mmol)和戊二酸(0.89g，6.77mmol)在水中(30ml)的悬浮液在70℃下搅拌过夜。过滤混合物，滤液蒸发至干，并在环境温度下在真空中进行干燥。分离得到标题化合物。收率1.23g(83％)。
实施例16
制备丙氨酸锶
将氢氧化锶八水合物(1.0g，3.79mmol)和L-丙氨酸(0.67g，7.52mmol)在水中(30ml)在室温下搅拌4小时。过滤混合物，滤液蒸发至干，并在环境温度下在真空中进行干燥。收率0.81g(63％)。
实施例17
制备马尿酸锶
将碳酸锶(0.5g，3.39mmol)和马尿酸(1.215，6.77mmol)在水(30ml)中在70℃下搅拌5小时。混合物过滤，滤液蒸发至干，并在环境温度下在真空中进行干燥。收率1.25g(83％)。
实施例18
1，2-二(2-氨基乙氧基)乙烷-N，N，N′，N′-四乙酸制备锶螯合物
碳酸锶(1.0g，6.77mmol)和1，2-二(2-氨基乙氧基)乙烷-N，N，N′，N′-四乙酸(2.58g，6.77mmol)在水(30ml)中在85℃下搅拌48小时。蒸发混合物，并在环境温度下在真空中进行干燥得到标题化合物。收率2.55g(81％)。
实施例4-18的化合物可以使用常规的药物载体和赋形剂配制成任何方便的形式服用。
实施例19
经皮渗透组合物
将40g氯化锶六水合物溶解在1000ml溶剂中，制备含锶组合物。溶剂的成分是：
50％(体积)蒸馏水
25％(体积)四甘醇(glucofurol)
25％(体积)DMSO
患有别奇捷列夫病(Bechterev disease)的两名病人使用非甾族消炎药和鸦片，但并没有减轻髂骶关节处的疼痛。在髂骶关节处经皮施用本实施例的组合物，每天给药两至三次。两个病人都观察到完全减轻疼痛。
实施例20
注射剂溶液
将从实施例13获得的锶EDTA二甲葡胺盐(20mg)溶于0.9％无菌水溶液(10ml)中并将其装入10ml小瓶中(带着橡皮塞的注射瓶)。溶液用高压消毒器进行杀菌。每毫升溶液含0.2mg的锶。
实施例21
含布洛芬、抗坏血酸锶和经皮渗透增强剂的水凝胶
使用研钵和杵将从实施例8获得的抗坏血酸锶(900mg)和月桂基硫酸钠(450mg)混合到Ibux凝胶5％(由Weifa AS，Oslo，Norway制备)中。(Ibux凝胶在包括羟乙基纤维素、苄醇、异丙醇、氢氧化钠和净化水的水凝胶中含5％的布洛芬)。所得的凝胶含1.2％wt的锶。
实施例22
包含布洛芬和氯化锶的水凝胶
用研钵和杵将氯化锶六水合物(0.8g)掺入Ibux凝胶5％(19.2g)。
实施例23
包含布洛芬和氯化锶的粘膜粘着剂水凝胶
用研钵和杵将聚丙烯酸5100钠盐(Fluka 81132)(0.21g)掺入含布洛芬和锶(参见实施例22)(7.0g)的水凝胶中。
实施例24
包含布洛芬和氯化锶的粘膜粘着剂水凝胶
将氯化锶六水合物(1.5g)和壳聚糖苹果酸(203-490-14SM从FMCBiopolymers，Drammen，Norway)(0.75g)掺入Ibux凝胶5％(12.75g)。所得粘膜粘着剂凝胶含3.3％wt的锶和5％wt的布洛芬。
实施例25
含氯化锶的乳剂
用研钵和杵将氯化锶六水合物(1.2g)掺入Unguentum Merck(13.8g)中。乳剂含2.6％wt的以氯化锶形式的锶。
实施例26
含氯化锶和一种经皮渗透增强剂的乳剂
用研钵和杵将氯化锶六水合物(1.2g)和月桂基硫酸钠(0.3g)掺入到Unguentum Merck(13.5g)中。乳剂含2.6％wt的以氯化锶形式的锶。
实施例27
含利多卡因和双氯芬酸锶的乳剂
用研钵和杵将从实施例11获得的双氯芬酸锶(40mg)掺入xylocain5％乳剂(Astra Zeneca AS，Oslo，Norway)。(100g Xylocains 5％乳剂含5克利多卡因在椰子油13.8g、聚氧乙烯酯4.5g、羧基聚亚甲基1g、氢氧化钠6.5g和净化水69g中)。乳剂包含5％wt的利多卡因和40mg/g的双氯芬酸锶。
实施例28
包含氢化可的松和硬脂酸锶的膏剂
用研钵和杵将从实施例12获得的硬脂酸锶(60mg)掺入氢化可的松1％膏剂(Galderma Nordic AB)中(包含1％氢化可的松、丙二醇、液体石蜡、十六醇和凡士林的氢化可的松1％膏剂)。所得膏剂包含1％wt的氢化可的松和3％wt的硬脂酸锶。
实施例29
包含锶布洛芬的粘膜粘着剂
用研钵和杵将从实施例10中获得的锶布洛芬(0.5g)掺入Orabase糊剂(Squibb AB，Lidingo，Sweden)(14.5g)中。Orabase包含明胶、果胶、羧甲基纤维素钠、聚乙烯和液体石蜡。所得配方包含3.3％wt的锶布洛芬，并且用于治疗口腔或其它粘膜体表的疼痛。
实施例30
实施例19的组合物的临床试验
一个七年前发生车祸的35岁妇女在颈部和肩部形成非常厉害的疼痛。该患者使用非甾族消炎药已经有很长一段时间，但是没有明显的效果。自从发生事故以来，她在哪一夜都不能连续地睡眠。
患者在疼痛的部位局部施用实施例19的组合物。她声称一分钟后感觉到疼痛减轻并且接下来的2-3天没有感觉到疼痛或感觉到微乎其微的疼痛。施用实施例13的组合物后的两夜中每夜她能够睡眠约10小时。
实施例31
实施例19的组合物的临床试验
脸上和/或手指疼痛的九个拳击手测试实施例19的组合物的效果。该组合物直接用于疼痛部位。这些拳击手在所有疼痛部位都感觉到立即的疼痛减轻。并且疼痛减轻可以存在很长时间。
鼻子和眼睛部位疼痛的四个拳击手测试组合物的效果，该组合物是2％wt的氯化锶六水合物在实施例19的相同溶剂中(即在实施例19中50％的锶浓度)。在疼痛减轻和疼痛部位的肿胀的减少方面，该制剂也显示良好的临床效果。
实施例32
从实施例19获得的组合物的临床试验
由于在怀孕期间没系韧带导致的骨盆腔部位疼痛的患者一段时间使用非甾族消炎药进行治疗，但是没有任何效果。
使用实施例19的局部制剂，立即导致疼痛减少。每使用一次，疼痛减轻效果延续约六小时。
实施例33
从实施例19获得的组合物的临床试验
在口腔部位具有单纯性疱疹感染的两个病人预先使用抗病毒乳剂(Zoviraxs(acylovir))具有中等的效果。抗病毒治疗的效果是疾病的发展好转，但是损伤有七至十天(没有治疗)。
这两个患者现在在损伤的八个不同爆发期间使用实施例19的组合物。局部施用该组合物完全阻止了损伤的发展并且使形成的伤口干燥。
Claims (17)
1.一种治疗人类或非人类患者皮下软组织疼痛的方法，其中所述的方法包括给所述的患者服用一种有效量的生理上可容忍的锶化合物。
2.权利要求1所述的方法，其中所述的锶化合物用于皮肤的表面。
3.权利要求1和2任意一项所述的方法，其中所述的软组织是肌肉。
4.一种生理上可容忍的锶化合物在制备用于治疗皮下软组织疼痛的药物中的用途。
5.一种减轻局部疼痛的药物组合物，包括一种生理上可容忍的锶化合物、一种生理上可容忍的载体和一种生理上可容忍的经皮渗透增强剂。
6.权利要求5所述的组合物，其中所述的经皮渗透增强剂是二甲亚砜。
7.一种减轻疼痛的药物组合物，包括一种生理上可容忍的锶化合物和一种生理上可容忍的生物粘合剂，任选连同一种生理上可容忍的载体或赋形剂。
8.权利要求5-7任意一项所述的组合物，其中所述的锶化合物是氯化锶或硝酸锶。
9.一种离子电渗装置，包括一个与药物贮存器电接触的阴极，其特征在于所述的药物贮存器包含一种生理上可容忍的锶化合物。
10.锶和生理上可容忍的非水杨酸盐、非昔康环加氧酶抑制剂的一种盐或络合物。
11.一种药物组合物，包括锶和生理上可容忍的非水杨酸盐、非昔康环加氧酶抑制剂的盐或络合物连同一种药物载体或赋形剂。
12.锶和一种α氨基酸的一种盐或络合物。
13.一种药物组合物，包括锶和一种α氨基酸的一种盐或络合物连同一种药物载体或赋形剂。
14.锶和一种生理上可容忍的二亚乙基三胺-或四氮杂环十二烷-骨架的螯合剂的一种盐或络合物。
15.一种药物组合物，包括锶和一种生理上可容忍的二亚乙基三胺-或四氮杂环十二烷-骨架的螯合剂的一种盐或络合物连同一种药物载体或赋形剂。
16.一种生理上可容忍的锶化合物在制备用于治疗疱疹感染的药物中的用途。
17.一种治疗人或其它哺乳动物患有的疱疹感染症状的方法，所述的方法包括给所述的患者服用一种有效量的生理上可容忍的锶化合物。
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102976997A (zh) * | 2009-05-27 | 2013-03-20 | 天津和美生物技术有限公司 | 阿伐他汀半锶盐多晶型物、其制备和作为HMG-CoA酶抑制剂的应用 |
| CN104363901A (zh) * | 2012-03-21 | 2015-02-18 | 美国考斯麦德生物科技有限公司 | 局部投与用于治疗疼痛、瘙痒症和炎症的含锶复合物 |
Families Citing this family (29)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6383519B1 (en) | 1999-01-26 | 2002-05-07 | Vita Special Purpose Corporation | Inorganic shaped bodies and methods for their production and use |
| NO20014746D0 (no) * | 2001-09-28 | 2001-09-28 | Clas M Kjoelberg | Smertelindrende middel |
| MXPA05004578A (es) * | 2002-10-31 | 2005-07-26 | Umd Inc | Composicion terapeutica para el suministro de drogas a y a traves de epitelios de proteccion. |
| WO2004084920A2 (en) * | 2003-03-27 | 2004-10-07 | Santosolve As | Anti-inflammatory treatment based on strontium compounds |
| CA2524610C (en) * | 2003-05-07 | 2014-03-25 | Osteologix A/S | Strontium combinations for prophylaxis/treatment of cartilage and/or bone conditions |
| AU2004237439B2 (en) * | 2003-05-07 | 2009-09-10 | Osteologix A/S | Treating cartilage/bone conditions with water-soluble strontium salts |
| PL1622629T3 (pl) * | 2003-05-07 | 2013-12-31 | Osteologix As | Kompozycja do kontrolowanego uwalniania zawierająca sól strontu |
| EP1523985B1 (en) * | 2003-10-17 | 2010-03-10 | Oy Neurofood Ab | Non-radioactive strontium agent for treating cancer |
| AU2005216596B2 (en) * | 2004-02-26 | 2011-03-24 | Osteologix A/S | Strontium-containing compounds for use in the prevention or treatment of necrotic bone conditions |
| DE602005025616D1 (de) * | 2004-02-26 | 2011-02-10 | Osteologix As | Strontiumhaltige verbindungen zur verwendung bei prävention oder behandlung nekrotisierender knochenkrankheiten |
| AU2005240257B2 (en) * | 2004-05-06 | 2011-11-24 | Osteologix A/S | High yield and rapid syntheses methods for producing metallo-organic salts |
| JP2008502609A (ja) * | 2004-06-17 | 2008-01-31 | オステオロジックス エイ／エス | リウマチおよび関節性疾患の治療改善方法 |
| AU2005254154A1 (en) * | 2004-06-17 | 2005-12-29 | Osteologix A/S | Improving pain treatment with strontium combinations |
| US20140099364A2 (en) | 2004-10-08 | 2014-04-10 | Forward Pharma A/S | Controlled release pharmaceutical compositions comprising a fumaric acid ester |
| GB2425060A (en) * | 2005-03-24 | 2006-10-18 | Santosolve As | Strontium compounds in cosmetics |
| RU2008104410A (ru) * | 2005-07-06 | 2009-08-20 | Остеологикс А/С (Dk) | Способы синтеза органических солей стронция с высоким выходом |
| WO2007137653A1 (en) | 2006-05-26 | 2007-12-06 | Baxter International Inc. | Injectable fibrin composition for bone augmentation |
| CA2686820C (en) * | 2007-04-23 | 2016-06-28 | Baxter International Inc. | Fibrin compositions containing strontium compounds |
| PT2379063E (pt) | 2009-01-09 | 2013-05-03 | Forward Pharma As | Formulação farmacêutica compreendendo um ou mais ésteres de ácido fumárico numa matriz de erosão |
| US8615888B2 (en) * | 2009-06-30 | 2013-12-31 | Dexter-Russell, Inc. | Impaired grip knife |
| WO2011041468A1 (en) | 2009-09-29 | 2011-04-07 | Georgia Tech Research Corporation | Electrodes, lithium-ion batteries, and methods of making and using same |
| WO2011140150A1 (en) | 2010-05-03 | 2011-11-10 | Georgia Tech Research Corporation | Alginate-containing compositions for use in battery applications |
| US9205041B2 (en) | 2011-05-03 | 2015-12-08 | Aponia Laboratories, Inc. | Transdermal compositions of ibuprofen and methods of use thereof |
| EP2530068A1 (en) | 2011-05-31 | 2012-12-05 | Lacer, S.A. | New strontium salts, synthesis and use thereof in the treatment of osteoporosis |
| US9480704B2 (en) | 2012-03-21 | 2016-11-01 | Cosmederm Bioscience, Inc. | Topically administered strontium-containing complexes for treating pain, pruritis and inflammation |
| WO2016141219A1 (en) * | 2015-03-05 | 2016-09-09 | Cosmederm Bioscience, Inc. | Strontium based compositions and formulations for pain, pruritus, and inflammation |
| US11235002B2 (en) | 2015-08-21 | 2022-02-01 | Galleon Labs Llc | Strontium based compositions and formulations for pain, pruritus, and inflammation |
| US20170049807A1 (en) * | 2015-08-21 | 2017-02-23 | Cosmederm Bioscience, Inc. | Strontium based compositions and formulations for pain, pruritus, and inflammation |
| US10463636B2 (en) | 2016-09-30 | 2019-11-05 | Deanna J. Nelson | Pharmaceutical quality strontium L-lactate |
Family Cites Families (40)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3865933A (en) * | 1972-05-24 | 1975-02-11 | C And A Lab Inc | Analgesic composition |
| US3988434A (en) * | 1972-08-07 | 1976-10-26 | Schole Murray L | Dental preparation |
| US4083965A (en) * | 1975-01-16 | 1978-04-11 | Bluhm Henry P | Method of and composition for relieving itch, pain and swelling resulting from insect stings and bites and skin contact with noxious plants |
| US4363818A (en) * | 1975-06-04 | 1982-12-14 | Gottlieb Sheldon K | Method for relief of burning, itching, and pain of cutaneous and mucosal surfaces |
| US4141359A (en) * | 1976-08-16 | 1979-02-27 | University Of Utah | Epidermal iontophoresis device |
| JPS6022946B2 (ja) * | 1976-09-24 | 1985-06-05 | 東レ株式会社 | 生体用透析装置の滅菌法 |
| JPS53148542A (en) * | 1977-05-27 | 1978-12-25 | Reiichi Yamaga | Pharmaceutical composition densistry |
| CA1179267A (en) | 1982-03-22 | 1984-12-11 | Larry Barron | Composition for relieving toothache pain |
| US4634589A (en) * | 1984-05-18 | 1987-01-06 | Wurttembergische Parfumerie-Fabrik Gmbh | Dentifrice for hypersensitive teeth |
| KR870700024A (ko) | 1984-07-12 | 1987-02-28 | 원본미기재 | 약, 비타민 또는 왁진의 근육내 주사용 제제 |
| JPH0742219B2 (ja) * | 1984-07-26 | 1995-05-10 | ライオン株式会社 | 口腔用組成物 |
| US4650668A (en) * | 1984-12-21 | 1987-03-17 | Larry Barron | Composition for relieving toothache pain and other forms of intense pain |
| US4756909A (en) * | 1986-04-28 | 1988-07-12 | Elena Avram | Method for relieving pain or producing analgesia with n-butanol |
| US5330746A (en) * | 1988-05-03 | 1994-07-19 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Dental varnish composition, and method of use |
| US4866046A (en) | 1988-05-31 | 1989-09-12 | Top Laboratories, Inc. | Low-dosage sublingual aspirin |
| JP2638635B2 (ja) * | 1989-01-31 | 1997-08-06 | 積水化学工業株式会社 | 経皮吸収製剤 |
| US5234971A (en) * | 1989-12-28 | 1993-08-10 | G-C Dental Industrial Corp. | Odontotherapeutical materials |
| US5855870A (en) * | 1990-03-22 | 1999-01-05 | Ultradent Products, Inc. | Method for treating sensitive teeth |
| US5851512A (en) * | 1990-03-22 | 1998-12-22 | Ultradent Products, Inc. | Dental compositions having a sticky matrix material for treating sensitive teeth |
| US5188818A (en) * | 1992-03-30 | 1993-02-23 | Isp Investments Inc. | Toothpaste composition containing strontium salt of maleic anhydride-methyl vinyl ether copolymer |
| US5260289A (en) * | 1992-06-12 | 1993-11-09 | Vitacain Pharmaceutical Co., Ltd. | Composition for treating pain, method for treating pain and composition for reinforcing pain relief action |
| JPH061721A (ja) | 1992-06-16 | 1994-01-11 | Bitakain Seiyaku Kk | 疼痛処置剤、及び疼痛軽減作用増強剤 |
| JPH08502976A (ja) | 1992-10-29 | 1996-04-02 | シー−ピー テクノロジー リミテッド パートナーシップ | カルシウムおよび硫酸塩を含有した組成物および複合体、その合成法、これを用いた治療法、これを含んでなる化粧用調製物 |
| US5380530A (en) * | 1992-12-29 | 1995-01-10 | Whitehill Oral Technologies | Oral care composition coated gum |
| GB9413873D0 (en) | 1994-07-09 | 1994-08-31 | Norbrook Lab Ltd | Long-acting oxytetracycline composition |
| US5716625A (en) * | 1994-12-21 | 1998-02-10 | Cosmederm Technologies | Formulations and methods for reducing skin irritation |
| US5804203A (en) * | 1994-12-21 | 1998-09-08 | Cosmederm Technologies | Topical product formulations containing strontium for reducing skin irritation |
| US6139850A (en) * | 1994-12-21 | 2000-10-31 | Cosmederm Technologies | Formulations and methods for reducing skin irritation |
| FR2732598B1 (fr) * | 1995-04-10 | 1997-05-09 | Oreal | Utilisation de sel de metaux alcalino-terreux pour le traitement des prurits et des dysesthesies oculaires ou palpebraux |
| EP0737471A3 (fr) * | 1995-04-10 | 2000-12-06 | L'oreal | Utilisation d'un sel d'une métal alcalino-terreux comme inhibiteur de TNF-alpha dans une composition unique et composition obtenue |
| FR2740341B1 (fr) * | 1995-10-26 | 1997-12-19 | Oreal | Utilisation de sel de lanthanide, d'etain, de zinc, de manganese, d'yttrium, de cobalt, de baryum, de strontium dans une composition pour la peau |
| US5958436A (en) * | 1995-12-21 | 1999-09-28 | Cosmederm Technologies | Formulations and methods for reducing skin irritation |
| US5922765A (en) | 1996-01-18 | 1999-07-13 | Fleming & Company, Pharmaceuticals | Methods and compositions for the prevention and treatment of muscle cramps and improving muscular strength |
| FR2749759B1 (fr) | 1996-06-17 | 1999-11-26 | Adir | Utilisation de sels de strontium pour l'obtention de compositions pharmaceutiques destinees au traitement de l'arthrose |
| US5914129A (en) | 1996-07-23 | 1999-06-22 | Mauskop; Alexander | Analgesic composition for treatment of migraine headaches |
| EP0834319A1 (en) | 1996-10-07 | 1998-04-08 | Kartar Dr. Lalvani | Mineral and vitamin combinations in arthritic pain |
| US6019997A (en) * | 1997-01-09 | 2000-02-01 | Minnesota Mining And Manufacturing | Hydroalcoholic compositions for transdermal penetration of pharmaceutical agents |
| US5958462A (en) * | 1997-05-23 | 1999-09-28 | Mclean; Linsey | Therapeutic bath salts and method of use |
| US6468809B1 (en) * | 2000-02-04 | 2002-10-22 | The United States Of America As Represented By The Secretary Of The Navy | High efficiency magnetic sensor for magnetic particles |
| NO20014746D0 (no) * | 2001-09-28 | 2001-09-28 | Clas M Kjoelberg | Smertelindrende middel |
-
2001
- 2001-09-28 NO NO20014746A patent/NO20014746D0/no unknown
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2002
- 2002-09-27 WO PCT/GB2002/004418 patent/WO2003028742A1/en active IP Right Grant
- 2002-09-27 EP EP02765057A patent/EP1429792B1/en not_active Expired - Lifetime
- 2002-09-27 US US10/488,162 patent/US7241460B2/en not_active Expired - Lifetime
- 2002-09-27 JP JP2003532073A patent/JP4750358B2/ja not_active Expired - Fee Related
- 2002-09-27 DE DE60225702T patent/DE60225702T2/de not_active Expired - Lifetime
- 2002-09-27 CA CA2499814A patent/CA2499814C/en not_active Expired - Fee Related
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- 2002-09-27 CN CNB028222628A patent/CN100415247C/zh not_active Expired - Fee Related
- 2002-09-27 AT AT02765057T patent/ATE389411T1/de active
- 2002-09-27 CN CNA2006101108362A patent/CN1981780A/zh active Pending
- 2002-09-27 PT PT02765057T patent/PT1429792E/pt unknown
- 2002-09-27 DK DK02765057T patent/DK1429792T3/da active
- 2002-09-27 EP EP06076548A patent/EP1741436A1/en not_active Withdrawn
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- 2007-06-11 US US11/808,487 patent/US20070237836A1/en not_active Abandoned
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102976997A (zh) * | 2009-05-27 | 2013-03-20 | 天津和美生物技术有限公司 | 阿伐他汀半锶盐多晶型物、其制备和作为HMG-CoA酶抑制剂的应用 |
| CN102976996A (zh) * | 2009-05-27 | 2013-03-20 | 天津和美生物技术有限公司 | 阿伐他汀半锶盐多晶型物、其制备和作为HMG-CoA酶抑制剂的应用 |
| CN102976996B (zh) * | 2009-05-27 | 2015-08-19 | 峡江和美药业有限公司 | 阿伐他汀半锶盐多晶型物、其制备和作为HMG-CoA酶抑制剂的应用 |
| CN104363901A (zh) * | 2012-03-21 | 2015-02-18 | 美国考斯麦德生物科技有限公司 | 局部投与用于治疗疼痛、瘙痒症和炎症的含锶复合物 |
| CN104363901B (zh) * | 2012-03-21 | 2017-03-22 | 美国考斯麦德生物科技有限公司 | 局部投与用于治疗疼痛、瘙痒症和炎症的含锶复合物 |
Also Published As
| Publication number | Publication date |
|---|---|
| CA2499814C (en) | 2011-07-26 |
| EP1741436A1 (en) | 2007-01-10 |
| CN100415247C (zh) | 2008-09-03 |
| US20070237836A1 (en) | 2007-10-11 |
| EP1429792A1 (en) | 2004-06-23 |
| ES2303860T3 (es) | 2008-09-01 |
| WO2003028742A1 (en) | 2003-04-10 |
| US7241460B2 (en) | 2007-07-10 |
| DE60225702T2 (de) | 2008-11-20 |
| JP4750358B2 (ja) | 2011-08-17 |
| CA2499814A1 (en) | 2003-04-10 |
| EP1429792B1 (en) | 2008-03-19 |
| US20150265649A1 (en) | 2015-09-24 |
| DE60225702D1 (de) | 2008-04-30 |
| NO20014746D0 (no) | 2001-09-28 |
| US20110038953A1 (en) | 2011-02-17 |
| US20050013877A1 (en) | 2005-01-20 |
| ATE389411T1 (de) | 2008-04-15 |
| DK1429792T3 (da) | 2008-07-14 |
| CN1981780A (zh) | 2007-06-20 |
| PT1429792E (pt) | 2008-07-01 |
| JP2005507396A (ja) | 2005-03-17 |
| US9050312B2 (en) | 2015-06-09 |
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