CN111280447A - 一种用于治疗和恢复骨关节功能的复合纳米制剂及制备方法 - Google Patents
一种用于治疗和恢复骨关节功能的复合纳米制剂及制备方法 Download PDFInfo
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Abstract
本发明公开了一种用于治疗和恢复骨关节功能的复合纳米制剂及制备方法。制剂包括:主料和辅料;主料和辅料的质量比范围是1:(0.10~0.15);所述主料包括:以丹参酮100mg为基准,丹参酮100mg;葡萄糖胺700~2500mg,透明质酸50~100mg,II型胶原蛋白100~300mg,硼50~150mg,花青素40~80mg。本发明能够保护关节及其连接组织免受自由基的引起的退化和侵害,从而给患者快速赢得行动自由提供了支撑。
Description
技术领域
本发明涉及医疗保健食品领域,具体是涉及一种用于治疗和恢复骨关节功能的复合纳米制剂及制备方法。
背景技术
关节是支持人类行走和肢体弯曲的最为重要的组织。随着经济发展和社会进步,人们追求生活和生命质量的意识大幅提高,增加体育运动已成为获得生命健康的主要方式,关节的致病率越来越高。
关节症的主要表现为关节疼痛和行动不力,主要包括:(1)生理性消耗和老化;(2)物理性损伤和摩擦;(3)病理性反应和炎症。
在过去的认识中,维持关节组成的基本物质(例如骨质)的流失导致了关节的生理性消耗、损伤、甚至器质性病变。因此,在一段时间内,中国的公众主要是通过服用(补充)钙来延缓骨质疏松,以及至今市场仍在流行的市场上开始出现围绕葡萄糖胺、胶原蛋白等而设计的单一或简单复合成分的商品(产品),以期维护关节的正常功能。
在正常情况下,通过弥补损失延缓病症产生,例如作为预防或治疗关节炎的营养剂,尤其是硫酸氨基葡萄糖和硫酸软骨素作为合成蛋白质多糖的基本组成部分,对促进骨关节完整性和维护骨关节健康具有重要作用。但从临床实践来看,应对已经发生病症的关节并尽快使其恢复自由运动,快速补充基本组分只是必要而非充分条件,因为除了关节本身器质性病变限制了运动功能外,关节工作环境尤其是关节的运动神经受损可能是导致关节功能受阻的重要原因。
运动神经的功能是众所周知的,本专利申请的创新在于依据健康骨关节和致病关节炎的解剖对比来理解关节炎的病理,并依此进行科学设计组分配比,快速有效应对关节应急障碍。
解剖研究发现,导致关节病理的两大主要因素是:一是随着年龄的增长,维持关节健康所需的成分的自然流失,导致关节衰老和功能减退,并进而引发器质性病变;二是运动量的增加或者不正确的运动方式,导致关节活动环境的改变,例如运动量的增加导致摩擦,磨损了维持关节活动的胶膜厚度,尤其是运动导致了关节滑液的温度快速升高,加速了有机组分的氧化过程,也就加速了软骨细胞的死亡。以上两种关节病理的出现如果得不到及时有效的救治,会通过损伤细胞并进而影响神经传导(严重者会损伤神经),使得关节致病及患者行动受阻。
现有产品多是简单组分添加葡萄糖胺或软骨素等,不仅吸收效率受限,而且对于改善已经发生病理的关节功能作用有限。本产品不仅重点补充受损关节的营养及其快速吸收,而且添加了花青素和丹参酮等成分,可快速对病理性关节进行系统性保护(例如能够增加伪胶膜厚度、阻止细胞氧化和衰老过程、保护关节神经、促进伤口愈合等)和全面修复(例如恢复细胞通讯和神经传导,恢复行动自由)。
发明内容
为解决现有技术中存在的问题,本发明提供了一种用于治疗和恢复骨关节功能的复合纳米制剂及制备方法。
本发明依据解剖发现并尽最大可能快速解决三大难题:1)针对关节病理结构和健康关节结构对比,测算并科学设计出需要快速补充的维系关节功能正常发挥所需要的最佳主成分配比,并通过高压均质方法获得其纳米晶体,快速、显著提高有效组分的吸收合成并大幅提高动物生物利用度和骨骼强度。2)寻找到一种新的组分(从葡萄种子中提取到)花青素,不仅能够增加伪胶膜厚度,能够有效抗氧化,抑制软骨细胞死亡,而且能够在骨关节损伤后迅速刺激和促进iNOS在骨关节细胞中枢神经系统及周围神经系统的神经组织内产生一氧化氮,进一步阻止细胞氧化过程,阻止关节细胞衰老,特别是对关节神经进行保护,协助细胞通讯及与原生膜联合。3)发现一种新组分(从中药丹参中提取)丹参酮,不仅具有抑菌、抗炎、降温、活血化瘀、促进伤口愈合等多方面作用,而且与花青素一起保护关节及其连接组织免受自由基的引起的退化和侵害,从而给患者快速赢得行动自由提供了支撑。
本发明的目的之一是提供一种用于快速治疗和恢复骨关节功能的复合纳米制剂。
主料和辅料;
主料和辅料的质量比范围是1:(0.10~0.15);
所述主料包括:
以丹参酮100mg为基准,
所述辅料为微晶纤维素、羟丙基纤维素、交联羧甲基纤维素钠、二氧化硅、硬脂酸镁、麦芽糊精中的一种或组合。
所述辅料包括:
以微晶纤维素100mg为基准,
微晶纤维素:100mg,
羟丙基纤维素:10-30mg;
交联甲羧纤维素钠:10-30mg;
麦芽糊精:30-50mg;
硬脂酸镁:1-3mg;
二氧化硅:1-3mg。
所述复合纳米制剂包括包衣材料;
所述主料和包衣材料的质量比为1:(0.12~0.20);
包衣材料为羟丙基甲基纤维素、改性玉米淀粉、云母、聚乙二醇、二氧化钛、三硅酸镁、甘油中的一种或组合。
所述包衣材料包括:
以羟丙基甲基纤维素100mg为基准;
本发明的目的之二是提供一种复合纳米制剂的制备方法。
包括:
(1)主料纳米晶体制备:
主料原料加入到十二烷基磺酸钠溶液中超声分散,再加入研磨珠,调节机器转速500-700r/min,每1.5-3.5h停机10-20min,研磨5-7h后停机,静置,将所得混悬液冷冻干燥7-9h,即主料纳米晶体;
(2)纳米辅料晶体制备:
所述辅料粉碎,过200-400目筛,加到6-9%的NaOH水溶液中,搅拌均匀,置-8--3℃冷冻,高压均质机均质处理,过滤洗涤后得纳米微晶纤维素。
(3)纳米素片的制备:
步骤(1)得到的纳米结晶和步骤(2)纳米微晶纤维素,均匀混合,制成素片。
(4)纳米包衣材料的制备:
将包衣原料用40-60%乙醇溶解配制成2-6%的溶液,搅拌均匀后过10-20目筛后备用;
(5)纳米薄膜包衣:
将步骤(3)所制备成的素片置于包衣锅中,热风将片子预热到30-50℃,均匀喷入步骤(4)制备的包衣液,增重得到覆盖有包衣的片剂;
片剂的硬度为5~20kgf、每片的质量为100~300mg。
本发明的主料成分及其功能
1、葡萄糖胺(Glucosamine)可补充关节润滑液,提供受损后关节恢复和软骨组织健康所必须的材料,恢复退化软骨的生理功能并促进软骨细胞生成,修复退化关节损伤。同时还可增加骨组织对钙的固定作用。避免钙质流失,增加骨密度。
2、透明质酸Joint Fluid(Hyaluronic Acid)一种天然多糖,不仅有保持皮肤弹性功能,还能锁住大量水分子,对组织具有保湿润滑作用,也是作为眼球水晶体、关节润滑液等物质的构成成分。
3.II型胶原蛋白(Type II Collagen)使用与健康软骨相同的蛋白质来帮助维持和修复软骨(cartilage)。这种独特的成分与你的免疫系统一起帮助保护软骨。
4.硼(Boron)通过保持健康水平的维生素D,钙和镁的水平,来维持健康的骨骼。因为关节从相邻的骨骼中获得基本营养素,健康的骨骼是健康关节的关键。
5.花青素(Anthocyanin)从葡萄种子中提取到的一种天然物质,不仅能够增加伪胶膜厚度,能够有效抗氧化,抑制软骨细胞死亡,而且能够在骨关节损伤后迅速刺激和促进iNOS在骨关节细胞中枢神经系统及周围神经系统的神经组织内产生一氧化氮,进一步阻止细胞氧化过程,阻止关节细胞衰老,特别是对关节神经进行保护,协助细胞通讯及与原生膜联合。
6.丹参酮(tanshinone),从中药丹参中提取到的一种天然物质,不仅具有保健功能(扩张冠状动脉,提高机体耐缺氧状况,提升机体免疫力的作用,因而能帮助机体抵抗外来病原体的入侵),而且具有抑菌、抗炎、降温、活血化瘀、促进伤口愈合等多方面作用。
二.辅料成分及其功能
片剂制备的辅料成分包括:纤维素Cellulose,羟丙基纤维素HydroxypropylCellulose,交联羧甲基纤维素钠Croscarmellose Sodium,二氧化硅Silicon Dioxide,硬脂酸镁Magnesium Stearate。
薄膜包衣制备的辅料成分包括:羟丙基甲基纤维素HydroxypropylMethylcellulose,改性玉米淀粉Modified Corn Starch,云母(彩色)Mica(Color),聚乙二醇Polyethylene Glycol,二氧化钛Titanium Dioxide,三硅酸镁Magnesium Trisilicate,甘油Glycerin。
经过正交试验设计、严格的组分筛选、多因素分析配比实验,最终确定主成分和辅料这些组分,以最优化的比例配合,保障纳米片剂的外观完整光洁、色泽均匀、含量和水分等有关物质的质量稳定、溶出度适宜。并在保证其疗效情况下,最大限度缩小片剂规格,是一款具有非常人性化设计的产品。
三.纳米制剂工艺改进
改进的工艺路线包括:主料纳米晶体的制备;辅料纳米晶体的制备;纳米片剂制备;纳米薄膜包衣
(1)主料纳米晶体制备:
主料原料加入到十二烷基磺酸钠溶液中超声分散,再加入研磨珠,调节机器转速500-700r/min,每1.5-3.5h停机10-20min,研磨5-7h后停机,静置,将所得混悬液冷冻干燥7-9h,即主料纳米晶体;
(2)纳米辅料晶体制备:
所述辅料粉碎,过200-400目筛,加到6-9%的NaOH水溶液中,搅拌均匀,置-8--3℃冷冻,高压均质机均质处理,过滤洗涤后得纳米微晶纤维素。
(3)纳米素片的制备:
按照主料和辅料的质量比分别称取相应质量的上述(1)超微纳米结晶和上述(2)纳米微晶纤维素,依次进行均匀混合,制成素片(颗粒或者初片)。
(4)纳米包衣材料的制备:
将包衣原料用40-60%乙醇溶解配制成2-6%的溶液,搅拌均匀后过10-20目筛后备用;
(5)纳米薄膜包衣:
复合纳米制剂的制备方法中的(3)所制备成的素片(颗粒或者初片)置于包衣锅中,热风将片子预热到30-50℃,均匀喷入(4)制备的包衣液,至片子增重到一定厚度(片重和硬度:片剂的硬度为5~20kgf、每片的质量为100~300mg)。
附图说明
图1非纳米形态粒径的扫描电镜图;
图2纳米晶体形态粒径的扫描电镜图;
图3实施例和对比例在Ph1.2的溶液中药物溶出曲线图;
图4实施例和对比例在Ph4的溶液中的药物溶出曲线图;
图5实施例和对比例在Ph6的溶液中的药物溶出曲线图;
图6实施例和对比例在蒸馏水中的药物溶出曲线图。
具体实施方式
下面结合实施例,进一步说明本发明。
实施例1:
称取所述主料135mg,所述主料包括:
以丹参酮100mg为基准,
所述辅料包括:
以微晶纤维素100mg为基准,
微晶纤维素:100mg,
羟丙基纤维素:15mg;
交联甲羧纤维素钠:15mg;
麦芽糊精:15mg;
硬脂酸镁:1.2mg;
二氧化硅:1.4mg。
所述包衣材料包括:
以羟丙基甲基纤维素100mg为基准,
按照所述主料和辅料的质量比范围1:0.12,主料和包衣材料的质量比1:0.16,分别称取辅料和包衣原料16.2mg、21.6mg,按照如下制备方法生产:
(1)主料纳米晶体制备:
主料原料加入到十二烷基磺酸钠溶液中超声分散,再加入研磨珠,调节机器转速500r/min,每1.5h停机10min,研磨5h后停机,静置,将所得混悬液冷冻干燥7h,即主料纳米晶体;
(2)纳米辅料晶体制备:
所述辅料粉碎,过200目筛,加到6%的NaOH水溶液中,搅拌均匀,置-5℃冷冻,高压均质机均质处理,过滤洗涤后得纳米微晶纤维素。
(3)纳米素片的制备:
按照主料和辅料的质量比分别称取相应质量的上述(1)超微纳米结晶和上述(2)纳米微晶纤维素,依次进行均匀混合,采用Φ8.5mm的浅凹形冲压模具制成素片(颗粒或者初片)。
(4)纳米包衣材料的制备:
将所取包衣材料用40%乙醇溶解配制成6%的溶液,搅拌均匀后过10-20目筛后备用;
(5)纳米薄膜包衣:
复合纳米制剂的制备方法中的(3)所制备成的素片(颗粒或者初片)置于包衣锅中,热风将片子预热到30℃,均匀喷入(4)制备的包衣液,至片子增重到一定厚度(硬度为8kgf)。片重:173mg。
实施例2:
称取所述主料180mg,所述主料包括:
以丹参酮100mg为基准,
所述辅料包括:
以微晶纤维素100mg为基准,
微晶纤维素:100mg,
羟丙基纤维素:20mg;
交联甲羧纤维素钠:20mg;
麦芽糊精:40mg;
硬脂酸镁:2mg;
二氧化硅:2mg。
所述包衣材料包括:
以羟丙基甲基纤维素100mg为基准,
按照所述主料和辅料的质量比范围1:0.13,主料和包衣材料的质量比1:0.17,分别称取辅料和包衣原料161.2mg、211.65mg,按照如下制备方法生产:
(1)主料纳米晶体制备:
主料原料加入到十二烷基磺酸钠溶液中超声分散,再加入研磨珠,调节机器转速600r/min,每2h停机15min,研磨6h后停机,静置,将所得混悬液冷冻干燥8h,即主料纳米晶体;
(2)纳米辅料晶体制备:
所述辅料粉碎,过300目筛,加到79%的NaOH水溶液中,搅拌均匀,置-5℃冷冻,高压均质机均质处理,过滤洗涤后得纳米微晶纤维素。
(3)纳米素片的制备:
按照主料和辅料的质量比分别称取相应质量的上述(1)超微纳米结晶和上述(2)纳米微晶纤维素,依次进行均匀混合,采用Φ8.5mm的浅凹形冲压模具制成素片(颗粒或者初片)。
(4)纳米包衣材料的制备:
将所取包衣原料用50%乙醇溶解配制成4%的溶液,搅拌均匀后过10目筛后备用。
(5)纳米薄膜包衣:
复合纳米制剂的制备方法中的(3)所制备成的素片(颗粒或者初片)置于包衣锅中,热风将片子预热到30℃,均匀喷入(4)制备的包衣液,至片子增重到一定厚度(硬度为10kgf)。片重:234mg.
实施例3:
称取所述主料100mg,所述主料包括:
以丹参酮100mg为基准,
所述辅料包括:
以微晶纤维素100mg为基准,
微晶纤维素:100mg,
羟丙基纤维素:12mg;
交联甲羧纤维素钠:11mg;
麦芽糊精:30mg;
硬脂酸镁:1mg;
二氧化硅:1mg。
所述包衣材料包括:
以羟丙基甲基纤维素100mg为基准;
按照所述主料和辅料的质量比范围1:0.12,主料和包衣材料的质量比1:0.18,分别称取辅料和包衣原料12mg、18mg,按照如下制备方法生产:
(1)主料纳米晶体制备:
主料原料加入到十二烷基磺酸钠溶液中超声分散,再加入研磨珠,调节机器转速600r/min,每2h停机20min,研磨6h后停机,静置,将所得混悬液冷冻干燥8h,即主料纳米晶体;
(2)纳米辅料晶体制备:
所述辅料粉碎,过300目筛,加到8%的NaOH水溶液中,搅拌均匀,置-5℃冷冻,高压均质机均质处理,过滤洗涤后得纳米微晶纤维素。
(3)纳米素片的制备:
按照主料和辅料的质量比分别称取相应质量的上述(1)超微纳米结晶和上述(2)纳米微晶纤维素,依次进行均匀混合,采用Φ10.5mm的浅凹形冲压模具制成素片(颗粒或者初片)。
(4)纳米包衣材料的制备:
将所选包衣原料用50%乙醇溶解配制成4%的溶液,搅拌均匀后过20目筛后备用。
(5)纳米薄膜包衣:
复合纳米制剂的制备方法中的(3)所制备成的素片(颗粒或者初片)置于包衣锅中,热风将片子预热到40℃,均匀喷入(4)制备的包衣液,至片子增重到一定厚度(硬度为11kgf)。片重:130mg
实施例4:
选取所述主料240mg,所述主料包括:
以丹参酮100mg为基准,
所述辅料包括:
以微晶纤维素100mg为基准,
微晶纤维素:100mg,
羟丙基纤维素:13mg;
交联甲羧纤维素钠:12mg;
麦芽糊精:30mg;
硬脂酸镁:1.5mg;
二氧化硅:1.5mg。
所述包衣材料包括:
以羟丙基甲基纤维素100mg为基准;
按照所述主料和辅料的质量比范围1:0.10,主料和包衣材料的质量比1:0.12,分别选取辅料和包衣原料24mg、28.8mg,按照如下制备方法生产:
(1)主料纳米晶体制备:
主料原料加入到十二烷基磺酸钠溶液中超声分散,再加入研磨珠,调节机器转速600r/min,每2h停机20min,研磨6h后停机,静置,将所得混悬液冷冻干燥8h,即主料纳米晶体;
(2)纳米辅料晶体制备:
所述辅料粉碎,过300目筛,加到8%的NaOH水溶液中,搅拌均匀,置-5℃冷冻,高压均质机均质处理,过滤洗涤后得纳米微晶纤维素。
(3)纳米素片的制备:
按照主料和辅料的质量比分别称取相应质量的上述(1)超微纳米结晶和上述(2)纳米微晶纤维素,依次进行均匀混合,采用Φ10.5mm的浅凹形冲压模具制成素片(颗粒或者初片)。
(4)纳米包衣材料的制备:
将所选包衣原料用50%乙醇溶解配制成4%的溶液,搅拌均匀后过20目筛后备用。
(5)纳米薄膜包衣:
复合纳米制剂的制备方法中的(3)所制备成的素片(颗粒或者初片)置于包衣锅中,热风将片子预热到40℃,均匀喷入(4)制备的包衣液,至片子增重到一定厚度(硬度为12kgf)。片重:293mg。
实施例5:
选取所述主料245mg,所述主料包括:
以丹参酮100mg为基准,
所述辅料包括:
以微晶纤维素100mg为基准,
微晶纤维素:100mg,
羟丙基纤维素:22mg;
交联甲羧纤维素钠:25mg;
麦芽糊精:45mg;
硬脂酸镁:2mg;
二氧化硅:2.1mg。
所述包衣材料包括:
以羟丙基甲基纤维素100mg为基准;
按照所述主料和辅料的质量比范围1:0.10,主料和包衣材料的质量比1:0.12,分别选取辅料和包衣原料24.5mg、29.4mg,按照如下制备方法生产:
(1)主料纳米晶体制备:
主料原料加入到十二烷基磺酸钠溶液中超声分散,再加入研磨珠,调节机器转速700r/min,每2h停机30min,研磨6h后停机,静置,将所得混悬液冷冻干燥8h,即主料纳米晶体;
(2)纳米辅料晶体制备:
所述辅料粉碎,过300目筛,加到9%的NaOH水溶液中,搅拌均匀,置-8℃冷冻,高压均质机均质处理,过滤洗涤后得纳米微晶纤维素。
(3)纳米素片的制备:
按照主料和辅料的质量比分别称取相应质量的上述(1)超微纳米结晶和上述(2)纳米微晶纤维素,依次进行均匀混合,采用Φ10.5mm的浅凹形冲压模具制成素片(颗粒或者初片)。
(4)纳米包衣材料的制备:
将所选包衣原料用60%乙醇溶解配制成6%的溶液,搅拌均匀后过30目筛后备用。
(5)纳米薄膜包衣:
复合纳米制剂的制备方法中的(3)所制备成的素片(颗粒或者初片)置于包衣锅中,热风将片子预热到60℃,均匀喷入(4)制备的包衣液,至片子增重到一定厚度(硬度为15kgf)。偏重299mg。
实施例6:
本发明配方功能测定:即通过大鼠药效学-骨密度和关节炎治疗效果研究,来测定发明配方的功效。
选取100—150gWistar大鼠25只,每组10只,雌雄各半,随机分为实施案例3制备的复合纳米产品组、普通片剂组(按照实施案例3配方制备的非纳米,即传统工艺生产:原辅料混合→制软材→制粒→烘干→压片→包衣而生产的主成分分布形态)、普通葡萄糖胺组、普通钙量组、自制鼠粮组、空白对照组。连续饲喂4周。每天称量大鼠体重,测定受试物对大鼠生长的作用。X骨密度仪检测大鼠骨密度。结果见表1。
表1 纳米制剂对生长、骨密度和生物利用度的影响
组别 | 动物数 | 平均增重率% | 骨密度变化g/cm2 |
空白对照组 | 10 | 25 | 0.014 |
普通鼠粮组 | 10 | 37 | 0.015 |
单药-葡萄糖胺组 | 10 | 41 | 0.022 |
单药-透明质酸组 | 10 | 40 | 0.022 |
单药-胶原蛋白组 | 10 | 39 | 0.023 |
单药-硼组 | 10 | 38 | 0.022 |
普通片剂组 | 10 | 51 | 0.027 |
纳米片剂组 | 10 | 71 | 0.037 |
结论
试验结果表明:1、本发明配方在所述功能(修复骨关节)上,明显有别于市场现有单一成分产品;2、以本发明配方量制备的纳米晶体与非纳米晶体相比,纳米晶体的功能更为明显。即:相对于单药制剂和普通片剂,本发明的复合纳米制剂组显著提高动物正常生长率、骨密度增长率和生物利用度等。
参考文献
1、新药研究指南,中华人民共和国卫生部药政管理局。
2、新药研究开发与申报技术审评学术会议资料汇编,北京中医药大学中药学院。2000,142-143。
实施例7:
对产品主成分纳米晶体的分布及形态测定
功能成分发挥实际效果的程度,主要跟功能成分被吸收的形态(粒径)大小有关,小分子成分总是优先被人体吸收。
对实施例3制备的复合纳米制剂采用粒度仪纳米晶体粒粒径和分散性;扫描电子显微镜确证纳米晶体形态;X射线衍射仪分析纳米晶的晶型特征;红外光谱仪扫描晶体化学结构。对比按照实施案例3配方制备的普通片剂(即传统工艺生产:原辅料混合→制软材→制粒→烘干→压片→包衣)产品中的主成分分布形态,结果显示,纳米晶体呈现较规则的棒状结构,粒径在100-300nm(人体优先吸收小分子)内,粒度分布较为均匀,分散性良好(见图1和图2)。
本实验解释了实施例6,本发明的同一配方产品中,相对于普通工艺生产的片剂,纳米制剂产品性能和稳定性得以显著提高。
实施例8:
产品成分吸收效果试验:溶出度实验
产品功能成分被吸收快慢,除了功能成分的粒径大小外,还关键依赖于功能成分的溶出速度。
参考中国药典溶出度测定法,对比按照实施案例3配方制备的非纳米(即传统工艺生产:原辅料混合→制软材→制粒→烘干→压片→包衣)产品形态试剂,和实施例1、实施例2、实施例3制备的复合纳米制剂晶进行体外溶出度测定。采用高效液相色谱法HPLC测定其峰面积,计算溶出量并绘制药物的溶出曲线。
结果显示:纳米片剂在pH=1.2的盐酸溶液、pH=6.0的磷酸盐缓冲液等溶出介质中,20min时溶出度均能达到80%以上,显示了较好的溶解度和溶出度;这表明,相比于普通片剂(即按照实施案例2配方制备的传统工艺生产:原辅料混合→制软材→制粒→烘干→压片→包衣产品),本复合纳米制剂处方工艺的重现性(产品溶出速率)良好。
Claims (8)
3.如权利要求1所述的用于治疗和恢复骨关节功能的复合纳米制剂,其特征在于:
所述辅料为微晶纤维素、羟丙基纤维素、交联羧甲基纤维素钠、二氧化硅、硬脂酸镁、麦芽糊精中的一种或组合。
5.如权利要求1~4之一所述的用于治疗和恢复骨关节功能的复合纳米制剂,其特征在于:
所述复合纳米制剂包括包衣材料;
所述主料和包衣材料的质量比为1:(0.12~0.20);
包衣材料为羟丙基甲基纤维素、改性玉米淀粉、云母、聚乙二醇、二氧化钛、三硅酸镁、甘油中的一种或组合。
7.一种如权利要求1~4之一所述的用于治疗和恢复骨关节功能的复合纳米制剂的制备方法,其特征在于所述方法包括:
(1)主料纳米晶体制备:
主料原料加入到十二烷基磺酸钠溶液中超声分散,再加入研磨珠,调节机器转速500-700r/min,每1.5-3.5h停机10-20min,研磨5-7h后停机,静置,将所得混悬液冷冻干燥7-9h,得到原料药的纳米晶体;
(2)纳米辅料晶体制备:
所述辅料粉碎,过200-400目筛,加到6-9%的NaOH水溶液中,搅拌均匀,置-8--3℃冷冻,高压均质机均质处理,过滤洗涤后得纳米微晶纤维素;
(3)纳米素片的制备:
步骤(1)得到的纳米结晶和步骤(2)纳米微晶纤维素,均匀混合,制成素片。
8.如权利要求7所述的复合纳米制剂的制备方法,其特征在于:
所述方法还包括:
(4)纳米包衣材料的制备:
将包衣原料用40-60%乙醇溶解配制成2-6%的溶液,搅拌均匀后过10-20目筛后备用;
(5)纳米薄膜包衣:
将步骤(3)所制备成的素片置于包衣锅中,热风将片子预热到30-50℃,均匀喷入步骤(4)制备的包衣液,增重得到覆盖有包衣的片剂;
片剂的硬度为5~20kgf、每片的质量为100~300mg。
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CN114028420A (zh) * | 2021-12-28 | 2022-02-11 | 杭州拾珍医疗器械有限公司 | 一种外用涂抹氨糖软骨素纳米制剂及其制备方法 |
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