CN109481450B - 一种用于预防和治疗白内障的眼用制剂及其制备方法 - Google Patents
一种用于预防和治疗白内障的眼用制剂及其制备方法 Download PDFInfo
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- CN109481450B CN109481450B CN201811324188.XA CN201811324188A CN109481450B CN 109481450 B CN109481450 B CN 109481450B CN 201811324188 A CN201811324188 A CN 201811324188A CN 109481450 B CN109481450 B CN 109481450B
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- ophthalmic
- excipient
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- lanosterol
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Abstract
本发明涉及一种用于预防和治疗白内障的眼用制剂，其特征在于：所述的眼用制剂包括羊毛脂烷型四环三萜类化合物和赋形剂，所述的羊毛脂烷型四环三萜类化合物和所述的赋形剂的质量比为1：9~30。本发明的眼用制剂质量稳定，制备工艺简单便捷，并进行了药效学评价。
Description
本申请是申请日为2016/8/22，申请号为2016106969925，发明创造名称为一种用于预防和治疗白内障的眼用制剂及其制备方法的发明专利的分案申请。
技术领域
本发明涉及一种用于预防和治疗白内障的眼用制剂及其制备方法。
背景技术
能引起晶状体代谢紊乱，导致晶状体蛋白质变性而发生混浊，称为白内障。多数白内障为老年性疾病，但也有儿童天生患有此病，还有人在受伤、炎症或生病后出现白内障。
据世界卫生组织不完全统计，全世界白内障盲人约有1600～2100万人。白内障一般病程缓慢，是眼科疾病中发病率最高的，也是最危险的，在不及时治疗或未注意预防的情况下很容易对眼睛造成损伤甚至失明。
白内障的治疗包括两个方面，一是药物治疗，二是手术治疗。早期及中期白内障患者可通过药物治疗，但目前尚无完全治愈的可能性，常等到成熟期，通过手术摘除混浊晶状体来恢复视力，但由于术后晶状体自身的结构破坏，而使其自身的调节能力丧失，并存在着发生多种并发症的可能性，因此寻求疗效确切的防治药物乃是重中之重。
(3β)-8,24-羊毛甾二烯-3-醇，俗称羊毛甾醇，是羊毛脂烷型四环三萜类化合物中的一种，英文名为lanosterol，CAS号为79-63-0，化学名为3β-Hydroxy-8,24-Lanostadiene，最近发现对患有白内障的狗施用含羊毛甾醇的眼药6周，可降低白内障的严重程度，提高晶状体的透明度，说明羊毛甾醇或具有相似活性分子的化合物，可以为治疗白内障提供另一种治疗手段，但是与羊毛甾醇相关的眼用制剂未见报道。
发明内容
本发明所要解决的技术问题是提供一种有效预防和治疗白内障的眼用制剂及其制备方法。
为了解决上述技术问题，本发明采用如下技术方案：
一种用于预防和治疗白内障的眼用制剂，以重量百分比计，其由0.1％～10％的羊毛脂烷型四环三萜类化合物和90％～99.9％的辅料组成。
优选地，所述的羊毛脂烷型四环三萜类化合物的占比为0.1％～5％，更有选为0.1％～2％。
优选地，所述的羊毛脂烷型四环三萜类化合物为羊毛甾醇。
优选地，所述的辅料为选自表面活性剂、等渗调节剂、防腐剂、抗氧化剂、基质、pH调节剂、促渗剂、赋形剂、稳定剂、有机溶剂、水中的一种或多种。
其中，表面活性剂又称为增溶剂。
进一步优选地，所述的表面活性剂为选自聚乙二醇-7-硬脂酸酯、二乙二醇单乙基醚、辛酸癸酸聚乙二醇甘油酯、硬脂酸聚烃氧(40)酯、聚氧乙烯(35)蓖麻油、聚乙二醇40氢化蓖麻油、卵磷脂、吐温-80、乙醇、聚乙二醇、卡波姆、泊洛沙姆和羟丙基-β-环糊精中的一种或几种的组合。
本发明中，所述的表面活性剂的添加量占所述的眼用制剂总质量的0.05％～25％，优选为0.1％～10％，最优选为0.1％～5％。
进一步优选地，所述的等渗调节剂为选自氯化钠、氯化钾、葡萄糖、甘露醇、丙二醇、丙三醇、硼酸、硼砂中的一种或几种的组合。
本发明中，所述的等渗调节剂的添加量占所述的眼用制剂总质量的0.05％～25％，优选为1％～15％，最优选为5％～12％。
进一步优选地，所述的防腐剂为选自三乙醇胺、硼酸、硼砂、枸橼酸钠、尼泊金甲酯、尼泊金乙酯、尼泊金丙酯、羟苯乙酯、硝酸苯汞、氯化苯甲烃铵溶液、羟苯乙酯、苯扎氯铵、苯扎溴铵、醋酸氯己定、聚季铵盐、三氯叔丁醇、苯乙醇、硫柳汞中的一种或几种的组合。
本发明中，所述的防腐剂的添加量占所述的眼用制剂总质量的0.0001％～1％，优选为0.0001％～0.1％，最优选为0.0001％～0.02％。
进一步优选地，所述的抗氧化剂为选自硫代硫酸钠、焦亚硫酸钠、亚硫酸氢钠、亚硫酸钠、依地酸二钠、丁羟茴醚、丁羟甲苯、α-生育酚、环己二胺四醋酸钠、N-羟基乙二胺三醋酸、二乙基三胺六醋酸、二巯乙基甘氨酸和乙二胺四乙酸、异抗坏血酸及其钠盐、硫脲中的一种或几种的组合。
本发明中，所述的抗氧化剂的添加量占所述的眼用制剂总质量的0.0001％～1％，优选为0.001％～0.1％，最优选为0.01％～0.02％。
进一步优选地，所述的基质为选自黄凡士林、白凡士林、羊毛脂、液体石蜡、透明质酸钠、聚乙烯醇、卡波姆、黄原胶、壳聚糖、木聚糖、聚丙烯酸、海藻酸钠、甲基纤维素、羟丙甲纤维素、聚维酮中的一种或几种的组合。
本发明中，所述的基质的添加量占所述的眼用制剂总质量的0.5％～90％，优选为1％～85％。
进一步优选地，所述的pH调节剂为选自氢氧化钠、盐酸、醋酸钠、碳酸钠、碳酸氢钠、磷酸氢二钠、磷酸二氢钠、硼酸、枸橼酸、枸橼酸钠中的一种或几种的组合。
本发明中，所述的pH调节剂的添加量占所述的眼用制剂总质量的0～15％。
进一步优选地，所述的促渗剂为选自卵磷脂、透明质酸钠、十二烷基硫酸钠、N-甲基吡咯烷酮、去氧胆酸钠、羟丙基-环糊精、月桂氮卓酮、乙二胺四乙酸二钠、吐温-80、丙二醇中的一种或几种的组合。
本发明中，所述的促渗剂的添加量占所述的眼用制剂总质量的0％～20％，优选为0.05％～20％，最优选为0.1％～0.5％。
优选地，所述的稳定剂为胆固醇、大豆磷脂、卵磷脂、单油酸甘油酯、硬脂、聚乙烯醇、聚乙二醇、羟丙甲纤维素、聚乙烯吡咯烷酮、泊洛沙姆中的一种或几种的组合。
本发明中，所述的稳定剂的添加量占所述的眼用制剂总质量的0％～90％，优选为0.05％～10％，最优选为1％～5％。
优选地，所述的赋形剂为甘露醇、右旋糖酐、乳糖、半乳糖、壳聚糖、精氨酸、葡甲胺、环糊精、明胶、葡萄糖、肌醇、蔗糖、海藻糖、山梨醇、木糖醇、白蛋白、蛋白胨、可溶性淀粉、糊精、阿拉伯胶、羟甲基纤维素、糖浆中的一种或几种的组合。
本发明中，所述的赋形剂的添加量占所述的眼用制剂总质量的0％～95％，优选为0.1％～20％，最优选为1％～10％。
优选地，所述的有机溶剂为氯仿、乙醇、丙酮、二甲亚砜、丙烯酸乙酯中的一种或几种的组合。
优选地，所述的水为注射用水。
优选地，所述的眼用制剂为滴眼液、眼膏、眼用凝胶、眼用冻干速溶片或眼用纳米脂质体。
优选地，以重量百分比计，所述的眼用制剂包括如下组分：
进一步优选地，以重量百分比计，所述的眼用制剂包括如下组分：
本发明中，当所述的眼用制剂为滴眼液时，以重量百分比计，所述的眼用制剂包括如下组分：
优选为，以重量百分比计，所述的眼用制剂包括如下组分：
优选地，以重量百分比计，所述的眼用制剂包括如下组分：
本发明中，当所述的眼用制剂为眼膏时，以重量百分比计，所述的眼用制剂包括如下组分：
优选地，以重量百分比计，所述的眼用制剂包括如下组分：
进一步优选地，以重量百分比计，所述的眼用制剂包括如下组分：
本发明中，当所述的眼用制剂为眼用凝胶时，以重量百分比计，所述的眼用制剂包括如下组分：
优选为，以重量百分比计，所述的眼用制剂包括如下组分：
进一步优选为，以重量百分比计，所述的眼用制剂包括如下组分：
优选地，以重量百分比计，所述的眼用制剂包括如下组分：
本发明中，当所述的眼用制剂为眼用冻干速溶片时，所述的眼用制剂包括羊毛脂烷型四环三萜类化合物和赋形剂，所述的羊毛脂烷型四环三萜类化合物和所述的赋形剂的质量比为1：9～30，优选为1：9～20，最优选为1：10～15。
以重量百分比计，所述的眼用制剂包括如下组分：
本发明中，当所述的眼用制剂为眼用纳米脂质体时，以重量百分比计，所述的眼用制剂包括如下组分：
优选地，以重量百分比计，所述的眼用制剂包括如下组分：
进一步优选地，以重量百分比计，所述的眼用制剂包括如下组分：
本发明的另一个目的是提供一种所述的用于预防和治疗白内障的眼用制剂的制备方法，将所述的羊毛脂烷型四环三萜类化合物和所述的辅料混合均匀得到所述的眼用制剂。
本发明中，当所述的眼用制剂为滴眼液时，该制备方法为：将所述的羊毛脂烷型四环三萜类化合物和所述的表面活性剂混合形成第一混合物，将所述的防腐剂和所述的水混合形成第二混合物，将所述的第一混合物和所述的第二混合物搅拌溶解后，经过热压灭菌即得所述的滴眼液。
优选地，所述的热压灭菌的温度为100～130℃，时间为20～40min。
本发明中，当所述的眼用制剂为眼膏时，该制备方法为：将所述的羊毛脂烷型四环三萜类化合物、所述的基质、所述的等渗调节剂、部分所述的抗氧化剂加热熔化形成油相，将所述的表面活性剂、剩余的所述的抗氧化剂、所述的防腐剂和部分所述的水加热溶解形成混合液，然后将所述的混合液加入所述的油相中，再加入剩余的所述的水，混合均匀即得所述的眼膏。
优选地，加热熔化的温度为70～80℃；加热溶解的温度为70～80℃。
本发明中，当所述的眼用制剂为凝胶时，该制备方法为：将所述的基质中加入所述的水进行润湿溶胀，然后加入所述的防腐剂，搅拌溶解形成第一混合液，将所述的羊毛脂烷型四环三萜类化合物和所述的表面活性剂混合形成第二混合液，然后将所述的第二混合液加入所述的第一混合液中，混合均匀即得所述的凝胶。
本发明中，当所述的眼用制剂为冻干速溶片时，该制备方法为：将所述的赋形剂溶解于所述的水中，然后加入所述的羊毛脂烷型四环三萜类化合物，分散均匀后冷冻干燥即得所述的冻干速溶片。
本发明中，当所述的眼用制剂为纳米脂质体时，该制备方法为：将所述的羊毛脂烷型四环三萜类化合物、所述的稳定剂分散于所述的有机溶剂中形成第一混合液，将所述的基质、所述的促渗剂分散于部分所述的水中，形成第二混合液，将所述的第一混合液分散于所述的第二混合液中，形成第三混合液，将所述的第三混合液减压旋蒸，得到纳米结晶混悬液，向所述的纳米结晶混悬液加入所述的抗氧化剂、所述的防腐剂、剩余的所述的水，混合均匀即得所述的纳米脂质体。
由于采用以上技术方案，本发明与现有技术相比具有如下优点：
本发明的眼用制剂对白内障的预防和治疗具有良好的疗效，且本发明的眼用制剂质量稳定，制备简单便捷。
说明书附图
图1为晶状体混浊程度分级示意图(Hiraoka T，1995)。
具体实施方式
下面结合具体实施例对本发明的技术方案作进一步的描述，但本发明不应限于这些实施例。
实施例1至5、对比例1：羊毛甾醇滴眼液的原料配方参见表1，制备方法为：称取羊毛甾醇加入表面活性剂中，搅拌，使其充分包合。称取防腐剂溶解于注射用水中。将防腐剂水溶液加入羊毛甾醇混合物中，搅拌溶解。热压灭菌，115℃、30min。
表1
实施例6至10、对比例2：羊毛甾醇眼膏的原料配方参见表2，制备方法为：称取羊毛甾醇、基质、等渗调节剂、部分抗氧化剂水浴上熔化，加热至75℃。另称取表面活性剂、剩余抗氧化剂、防腐剂溶于部分注射用水中，加热至75℃。缓慢加入油相中，边加边搅拌，加剩余注射用水，混合均匀。
表2
实施例11至15、对比例3：羊毛甾醇凝胶的原料配方参见表3，制备方法为：将基质加入注射用水中润湿溶胀，加入防腐剂，搅拌溶解。将羊毛甾醇加入表面活性剂中搅拌溶解。然后将羊毛甾醇溶液缓慢加入基质溶液中，搅拌混合均匀。
表3
实施例16至20、对比例4：羊毛甾醇眼用冻干速溶片的原料配方参见表4，制备方法为：将赋形剂加入注射用水中搅拌溶解，再加入羊毛甾醇分散均匀，灌装于准备好的泡罩中，冷冻干燥而得。
另一5ml滴眼液瓶中装有缓冲液。使用时旋开滴眼液瓶大瓶盖，用拇指将药片压出投入瓶中，旋紧瓶盖振摇。
表4
实施例21至25、对比例5：羊毛甾醇纳米脂质体的原料配方参见表5，制备方法为：将羊毛甾醇、稳定剂、分散于有机溶剂中，得溶液1。将基质、促渗剂溶胀分散于部分注射用水中，得溶液2。将溶液1高速剪切或超声分散于溶液2中，得溶液3。将溶液3减压旋蒸，得纳米结晶混悬液，为溶液4。在溶液4中加入抗氧化剂、防腐剂、剩余注射用水，混合均匀。
表5
实施例1至25、对比例1至5的眼用制剂对白内障的治疗作用研究
SD大鼠，于幼鼠颈背部皮下注射2mmol/L浓度的亚硒酸钠溶液，注射剂量为25μmol/kg。
造模4天后(D5)，在裂隙灯下检查晶状体混浊程度并照相，按Hiraoka T分级法对晶状体混浊程度进行分级，共分为7级，详见表6。裂隙灯照相取一张眼正位弥散光下全眼照片及一张眼侧位裂隙光下(裂隙光右侧40°，裂隙光宽2mm)照片，详见图1。
表6
动物建模前随机选出8只不做任何处理作为正常对照组，D5在建模动物中挑选晶状体混浊程度1～3级的动物入组，根据晶状体混浊程度进行分组，保证在分组时晶状体混浊程度无显著差异。分别为模型对照组、实施例1至25的实验组、对比例1至5的对比组和阳性对照组，每组8只。
模型对照组给予溶媒。
实验组和对比组，分别滴眼给予实施例1至25、对比例1至5中的滴眼液，给药剂量为0.015mg/眼。
阳性对照组，滴眼给予法可林0.00225mg/眼。
各给药组每日给药4次，连续给药6周(D5～D47)。
给药容量：15μl/眼/次，双眼给药。
考察内容(1)一般临床观察，试验期间每天观察所有动物一次，观察死亡、发病、呼吸、分泌物、粪便以及饮食、饮水情况等。经过47天观察发现所有动物均未见异常。
(2)分别于D5、D7、D12、D19、D26、D33、D40、D47对晶状体混浊程度进行分级，并对晶状体混浊斑块进行直径测量，记录每只动物眼睛晶状体混浊斑块直径大小。各组动物白内障例数总结详见表7，晶状体混浊斑块平均直径总结详见表8。
表7
表8
评价药物对白内障晶状体的生理生化产生改变时，硒性白内障模型是最常使用的动物模型，这一模型的特点、应用及其与人类白内障的关系已有综述。羊毛甾醇眼用制剂对1级和2级SD大鼠硒性白内障的进展有一定的延缓作用，意味可以控制白内障的进展，对3级白内障具有一定的康复和治疗作用。将羊毛甾醇眼用制剂与市售法可林滴眼液进行药效学对比，试验结果显示，在早期白内障的治疗效果上，羊毛甾醇滴眼液明显好于法可林滴眼液。
Claims (3)
1.一种用于预防和治疗白内障的眼用制剂，其特征在于：所述眼用制剂为眼用冻干速溶片，所述眼用冻干速溶片由如下组分组成：羊毛甾醇5g、赋形剂甘露醇45g、赋形剂明胶25g；
或，所述眼用冻干速溶片由如下组分组成：羊毛甾醇5g、赋形剂木糖醇40g、赋形剂阿拉伯胶10g；
或，所述眼用冻干速溶片由如下组分组成：羊毛甾醇5g、赋形剂白蛋白45g、赋形剂环糊精26.6g；
或，所述眼用冻干速溶片由如下组分组成：羊毛甾醇5g、赋形剂乳糖25g、赋形剂精氨酸25g；
或，所述眼用冻干速溶片由如下组分组成：羊毛甾醇5g、赋形剂环糊精26.6g、赋形剂明胶25g。
2.一种如权利要求1所述的用于预防和治疗白内障的眼用制剂的制备方法，其特征在于：将所述的赋形剂溶解于500mL水中，然后加入所述的羊毛甾醇，分散均匀后冷冻干燥即得所述的眼用制剂。
3.根据权利要求2所述的制备方法，其特征在于：所述的水为注射用水。
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| DK3536698T3 (da) | 2017-01-25 | 2021-09-27 | Guangzhou Ocusun Ophthalmic Biotechnology Co Ltd | Lanosterol-prodrugforbindelse og anvendelse deraf |
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Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA837050A (en) * | 1970-03-17 | L. Bouthelier Jean | Method of and composition for the treatment of human carcinoma and hypercholestrolemia | |
| CN1209811A (zh) * | 1996-01-22 | 1999-03-03 | 塞拉麦克思实验室公司 | 新型的19－去－孕甾烯衍生物 |
| CN101060850A (zh) * | 2005-05-17 | 2007-10-24 | 森永乳业株式会社 | 改善胰腺功能的药物和食品或饮料 |
| WO2013063279A1 (en) * | 2011-10-25 | 2013-05-02 | The Trustees Of Princeton University | A high-loading nanoparticle-based formulation for water-insoluble steroids |
| CN103370053A (zh) * | 2011-01-31 | 2013-10-23 | Ip科技有限公司 | 类胡萝卜素颗粒及其应用 |
| CN104352361A (zh) * | 2014-11-20 | 2015-02-18 | 广州神采化妆品有限公司 | 一种可变色的透明唇膏及其制备方法 |
| WO2016029199A1 (en) * | 2014-08-22 | 2016-02-25 | Kang Zhang | Compositions and methods to treat vision disorders |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009107753A1 (ja) * | 2008-02-29 | 2009-09-03 | 財団法人 名古屋産業科学研究所 | 後眼部到達用リポソーム及び後眼部疾患用医薬組成物 |
| MX2011001411A (es) * | 2008-08-05 | 2011-03-15 | Amazonia Fitomedicamentos Ltda | Usos farmaceuticos de lanosta-8,24-dien-3-ols. |
-
2016
- 2016-08-22 CN CN201610696992.5A patent/CN106074568B/zh active Active
- 2016-08-22 CN CN201811324475.0A patent/CN109364020B/zh active Active
- 2016-08-22 CN CN201811324188.XA patent/CN109481450B/zh active Active
- 2016-08-22 CN CN201811324473.1A patent/CN109364019B/zh active Active
- 2016-08-22 CN CN201811324187.5A patent/CN109481392B/zh active Active
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA837050A (en) * | 1970-03-17 | L. Bouthelier Jean | Method of and composition for the treatment of human carcinoma and hypercholestrolemia | |
| CN1209811A (zh) * | 1996-01-22 | 1999-03-03 | 塞拉麦克思实验室公司 | 新型的19－去－孕甾烯衍生物 |
| CN101060850A (zh) * | 2005-05-17 | 2007-10-24 | 森永乳业株式会社 | 改善胰腺功能的药物和食品或饮料 |
| CN103370053A (zh) * | 2011-01-31 | 2013-10-23 | Ip科技有限公司 | 类胡萝卜素颗粒及其应用 |
| WO2013063279A1 (en) * | 2011-10-25 | 2013-05-02 | The Trustees Of Princeton University | A high-loading nanoparticle-based formulation for water-insoluble steroids |
| WO2016029199A1 (en) * | 2014-08-22 | 2016-02-25 | Kang Zhang | Compositions and methods to treat vision disorders |
| CN104352361A (zh) * | 2014-11-20 | 2015-02-18 | 广州神采化妆品有限公司 | 一种可变色的透明唇膏及其制备方法 |
Non-Patent Citations (1)
| Title |
|---|
| Lanosterol reverses protein aggregation in cataracts;Ling Zhao et al.;《nature》;20150730;第523卷;第607-611页及摘要；Preparation of drug-loaded nanoparticles部分；25mM lanosterol in the topical vehicle solution部分 * |
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