CN110840946A - 一种治疗关节疼痛、腰腿酸痛制剂的制备方法 - Google Patents
一种治疗关节疼痛、腰腿酸痛制剂的制备方法 Download PDFInfo
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Abstract
本发明公开了一种治疗关节疼痛、腰腿酸痛制剂的制备方法,将制川乌、制草乌、防已、防风、续断、牛膝、桂枝、威灵仙、老鹳草的提取清膏置填充有D101大孔树脂的层析柱柱顶,乙醇洗脱,收集洗脱液浓缩成浸膏;将浸膏加入海藻酸钠溶液中,搅拌制成水相;取液体石蜡和聚山梨酯加热混匀制得油相;将水相缓慢加入油相中,迅速降温后加入异丙醇,静置,过滤,分离,取固体物真空干燥,得微囊;取微囊加入助剂,混匀,压片,包衣,即得。本发明可明显提高制剂的稳定性、有效性,药物释放稳定、平缓,明显降低药物的毒副作用,提高药物生物利用度。该制备方法的工艺简单、容易操作、生产成本低,容易实现工业化生产,具有良好的推广前景。
Description
技术领域
本发明涉及一种治疗关节疼痛、腰腿酸痛制剂的制备方法。
背景技术
风湿骨痛是风寒湿邪侵入人体所致、风寒湿邪侵入人体后,导致筋脉阻塞不通,“不通则痛”,由此常引起人体关节、骨膜、肌肉等部位发生红肿疼痛,主要症状有关节疼痛、晨僵(患者晨起或休息较长时间后,关节呈胶粘样僵硬感,活动后方能缓解或消失)、关节肿胀和压痛(出现在有疼痛的关节,是滑膜炎或周围软组织炎的体征,其程度因炎症轻重不同而异)以及关节肿痛(指关节丧失其正常的外形和活动范围受到限制,如膝不能完全伸直,手的掌指关节有尺侧偏斜,关节半脱位等),在上述症状中,晨僵在类风湿关节炎中最为突出,可以持续数小时,在其他关节炎则持续时间较短;关节肿胀和压痛可由关节腔积液或滑膜肥厚所致;关节肿痛与软骨和骨遭破坏有关,在类风湿关节炎中常见。风湿骨病具有缓慢性、游走性、多发性、对称性、呈梭性、致残性、血清类风湿因子化验呈阳性,活动期血沉加快等特点。
我国中老年人群中97%患有腰椎疾病,其中并发性神经型腰椎痛高发。近年来,又呈现出年轻化的趋势,40岁以下人群发病高达25%以上,中医认为本病属中医学“骨痿”范畴,多因肾虚精亏、肾阳虚衰不能充骨生髓,肾阴不足、精失所养,不能养髓。
腰腿疼痛指的是脊柱脊髓外科门诊常见病症。腰部疼痛主要包括劳损性疼痛(软组织疼痛),间盘源性疼痛,风湿性疾病。腿部疼痛主要包括腰间盘突出症、关节炎、血管性疾病、风湿性疾病。
目前国内外治疗神经型腰椎痛尚无有效的治疗药物,中医主要是以补肝肾,祛风湿,消肿止痛,舒筋活血为主,辅以现有的中草药进行治疗。按摩与固定制动、手法推拿是靠外力的作用,只能起到暂时的止痛作用,而不能达到治疗的目的。针灸法可通经活血并有止痛作用,可消除疼痛,但对神经型腰椎痛来说针灸只能起辅助作用。医治疗本病主要依靠药物治疗,封闭疗法是药物注射于痛点和神经根周围,但是对人体伤害较大,不宜常用。物理治疗是通过各种物理因子作用于人体(如红外线、磁、电),起到消炎、止痛、加速恢复的目的、对改善临床症状是十分有效的,但是对人体有一定的伤害。手术治疗主要用于严重影响生活、工作和休息者,经非手术疗法无效者。手术改变了人体原有的组织结构,属于创伤性疗法。患者比较痛苦,手术破坏人体组织,造成人体组织结构的改变,容易增加其它组织的病变,比如,有些患者,在术后一段时间后,容易引发其它腰间盘的退变或造成不同程度的膨出或突出,还容易产生神经沾连或腿脚麻木,失去知觉,尤其容易引发骨质增生或椎骨不稳。所以手术疗法只能在不得已时采用,腰突症在某种程度上属于自限性或自愈性疾病,应尽量选用保守疗法。
风湿灵片的处方是由制川乌、制草乌、防己、防风、续断、牛膝、桂枝、威灵仙和老鹳草九味中药组成。最早的风湿灵片处方收载于卫生部药品标准中药成方制剂第三册50页,标准代号为WS3-B-0518-91,具有祛风散寒,舒筋活络,用于治疗风寒湿痹、关节痛疼、手足麻木、腰腿酸痛。部颁标准其制备方法为:取制川乌68g、制草乌102g、防已136g、防风68g、续断68g、牛膝68g、桂枝68g、威灵仙68g、老鹳草136g,加水煎煮二次,第一次3小时,第二次2小时,合并煎液,滤过,滤液减压浓缩成稠膏,加淀粉适量,混匀,制成颗粒,干燥,压制成1000片,包糖衣,即得。
如中国专利CN105362424A公开了“一种风湿灵片及其制备方法”,包括以下步骤:将枳实80g、香加皮180g、威灵仙240g、桑寄生240g、苍术145g采用额氧化碳超临界萃取法提取,减压干燥,用高能纳米冲击磨粉碎成纳米干膏,加入功能性辅料(微晶纤维素、羟丙纤维素、交联羧甲基纤维素、硅酸镁铝、氯化钠、甘露醇、麦芽糊精),制成风湿灵片(素片),该药崩解时间显著缩短,疗效显著优于市售风湿灵片。但本品为素片,没有衣层的保护,且其甘露醇等辅料吸湿性较强,贮存过程容易吸潮导致片剂表面出现花斑等影响成品质量的现象,甚至可能会引起一些不良反应的发生。
目前市售的风湿灵片为上世纪九十年代初期的产品,但由于当时条件限制以及制备技术地下等原因,仅仅简单的水煎煮浓缩后制成片剂,大部分杂质未能剔除,使得制成的片剂不但服用量大的离谱(每次10片,一日2次),服用后存在着溶变时间长、生物利用度较低等问题,大大影响药物的有效性及稳定性,也直接影响着治疗的效果。
而且,据资料显示,风湿灵片处方中主要成分制川乌、制草乌的主要有效成分为乌头碱及次乌头碱等生物碱,具有一定的毒性,可使迷走神经兴奋,对周围神经损害,中毒症状以神经系统和循环系统的为主,其次是消化系统症状。临床主要表现为口舌及四肢麻木,全身紧束感等,通过兴奋迷走神经而降低窦房结的自律性,引起易位起搏点的自律性增高而引起各心律失常,损害心肌。一般情况下,口服纯乌头碱0.2mg(200ug)即可中毒,3-5mg可致死。因此,有必要改变制备工艺,提高制剂稳定性及有效性,控释药物释放速度,降低药物的毒副作用,提高药物生物利用度,以满足临床治疗和家庭使用的多种需求,特别是要严格控制制剂中乌头总碱的含量,大大降低其毒性,以保证患者用药安全、有效。
发明内容
本发明的目的在于克服现有技术存在的缺陷,提供一种风湿灵片,即“一种治疗关节疼痛、腰腿酸痛制剂”的制备方法。新制备的制剂可明显提高制剂的稳定性、有效性,药物释放稳定、平缓,明显降低药物的毒副作用,提高药物生物利用度。该制备方法的工艺简单、容易操作、生产成本低,容易实现工业化生产。
为了实现上述目的,本发明采用的技术方案如下:
本发明的治疗关节疼痛、腰腿酸痛制剂的制备方法,包括以下步骤:
(1)分别取处方量的制川乌100份、制草乌100份、防已100份、防风100份、续断100份、牛膝100份、桂枝100份、威灵仙100份和老鹳草100份,加水煎煮2-3次,每次加水量为药材总重量的6-8倍、提取时间为2-3小时,合并煎液,滤过,滤液减压浓缩成65℃下相对密度为1.10-1.20的清膏;
(2)取清膏置入填充有D101大孔树脂的层析柱柱顶,用体积分数为55-65%乙醇进行洗脱,收集清膏体积4倍量的洗脱液,回收乙醇,继续浓缩成65℃下相对密度为1.30-1.35的浸膏;
(3)将海藻酸钠置于配料锅中,加水并在80-90℃下加热使海藻酸钠溶解,得质量分数为20%海藻酸钠溶液,再加入浸膏,搅拌使浸膏充分混溶于海藻酸钠溶液中,制成水相;取液体石蜡置于配料锅中,再加入聚山梨酯80,加热至80-90℃,混匀,制成油相;
(4)控制油相的温度为75-80℃,搅拌,将所述水相缓慢加入油相中,继续搅拌10min,制成混悬液;混悬液降温至20-30℃后再加入占混悬液总体积3-5%的异丙醇,静置18-24h,得静置液;取静置液过滤,分离固液相,固体物真空干燥,得微囊;
(5)按照以下重量份数称取各原料:微囊100份、羟丙基甲基纤维素25-30份、乳糖9-10份、微晶纤维素35-40份、十二烷基硫酸钠8-10份、聚乙烯比咯烷酮8-10份、微粉硅胶1份,混匀,压制成素片,薄膜包衣,即得。
优选地,所述微囊的水分≤6%。
优选地,所述步骤(3)、(4)的搅拌速度为1500-2000rpm。
优选地,所述步骤(4)的真空干燥温度为60℃-70℃,时间为10-12小时。
优选地,所述步骤(5)的片重为0.30-0.35g。
优选地,所述步骤(2)的清膏与D101大孔树脂的质量比为5:1。
优选地,所述步骤(3)中浸膏和海藻酸钠的质量比为1:1;浸膏、液体石蜡、聚山梨酯的质量比为1:1.2:6。
利用本发明的制备方法制成的片剂,乌头总碱≦20ug/片、汉防己甲素≥3.0mg/片。
本发明采用的中药材来源和功效如下:
制川乌,为川乌(毛茛科植物乌头Aconitum carmichaeli Debx.的干燥母根)的炮制加工品。辛、苦,热;有毒。归心、肝、肾、脾经。同川乌。祛风除湿,温经止痛。用于风寒湿痹,关节疼痛,心腹冷痛,寒疝作痛,麻醉止痛。
制草乌,为草乌(为毛茛科植物北乌头Aconitum kusnezoffii Reichb.的干燥块根)的炮制加工品。辛、苦,热;有毒。归心、肝、肾、脾经。祛风除湿,温经止痛。用于风寒湿痹,关节疼痛,心腹冷痛,寒疝作痛,麻醉止痛。
防己,为防己科植物粉防己Stephania tetrandra S.Moore的干燥根。苦,寒。归膀胱、肺经。利水消肿,祛风止痛。用于水肿脚气,小便不利,湿疹疮毒,风湿痹痛;高血压。
防风,为伞形科植物防风Saposhnikovia divaricata(Turcz.)Schischk.的干燥根。辛、甘,温。归膀胱、肝、脾经。解表祛风,胜湿,止痉。用于感冒头痛,风湿痹痛,风疹瘙痒,破伤风。
续断,为川续断科植物川续断Dipsacus asperoides C.Y.Cheng et T.M.Ai(或Dipsacus asper Wall)的干燥根。苦、辛,微温。归肝、肾经。补肝肾,强筋骨,续折伤,止崩漏。用于腰膝酸软,风湿痹痛,崩漏,胎漏,跌扑损伤。酒续断多用于风湿痹痛,跌扑损伤。盐续断多用于腰膝酸软。
牛膝,为苋科植物牛膝Achyranthes bidentata Blume.的干燥根。苦、酸,平。归肝、肾经。补肝肾,强筋骨,逐瘀通经,引血下行。用于腰膝酸痛,筋骨无力,经闭症瘕,肝阳眩晕。
桂枝,为樟科植物肉桂Cinnamomum cassia Presl的干燥嫩枝。辛、甘,温。归心、肺、膀胱经。发汗解肌,温通经脉,助阳化气,平冲降气。用于风寒感冒,脘腹冷痛,血寒经闭,关节痹痛,痰饮,水肿,心悸,奔豚。
威灵仙,为毛茛科植物威灵仙Clematis chinensis Osbeck、棉团铁线莲(山蓼)Clematis hexapetala Pall.或东北铁线莲(黑薇)Clematis manshurica Rupr.的干燥根及根茎。辛、咸,温。归膀胱经。祛风除湿,通络止痛。用于风湿痹痛,肢体麻木,筋脉拘挛,屈伸不利,骨哽咽喉。
老鹳草,为牻牛儿苗科植物牻牛儿苗Erodium stephanianum Willd.、老鹳草Geranium Wilfordii Maxim.或野老鹳草Geranium carolinianum L.的干燥地上部分。辛、苦,平。归肝、肾、脾经。祛风湿,通经络,止泻利。用于风湿痹痛,麻木拘挛,筋骨酸痛,泄泻痢疾。
本发明由于采用了上述技术方案,具有以下有益效果:
1、本发明在原风湿灵片药材提取工艺的基础上,将药材浸膏的制备工艺进行了优化,增加了大孔树脂对药材清膏的提纯工艺,有效剔除了大部分杂质,大大减少辅料用量,而且还能有效降低杂质可能对人体的毒副作用。
2、本发明方法将药材浸膏微囊化并压制成薄膜衣片后可明显降低制剂的引湿性,使药物在生产、贮存过程不易受潮变质,能提高风湿灵片的的稳定性、有效性。
3、本发明方法将浸膏微囊后具有一定的缓控释性能,释放度与市售的风湿灵片相比明显降低,药物释放缓慢且平稳,既可防止药物在胃内失活或减少对胃的刺激性,又能提高药物的生物利用度。
4、本发明以海藻酸钠作为微囊壁材,原料来源广泛,价格低廉,具有很好的水溶性和乳化性,能够较好的对药物进行包合。
5、本发明方法得到的制剂的服用量由目前市售风湿灵片的10片/次缩减为5片/次,每日服用2次缩减为1次,减轻了患者身体负担。
6、经过检测,本发明方法得到的制剂的含量范围为:乌头总碱≦20ug/片、汉防己甲素≥3.0mg/片,有效降低了乌头碱的含量。
7、本发明方法的工艺简单、容易操作、耗能低、省时、生产成本低,容易实现工业化生产。
附图说明
图1为药物释放曲线。
具体实施方式
为使本发明的目的、技术方案及优点更加清楚明白,以下举出优选实施例,对本发明进一步详细说明。然而,需要说明的是,说明书中列出的许多细节仅仅是为了使读者对本发明的一个或多个方面有一个透彻的理解,即便没有这些特定的细节也可以实现本发明的这些方面。除非另有说明,本发明中的乙醇量的百分数是体积百分数,v/v表示溶液的体积比。
实施例1
一种治疗关节疼痛、腰腿酸痛制剂的活性成分的制备方法,包括以下步骤:
(1)分别取处方量的制川乌100份、制草乌100份、防已100份、防风100份、续断100份、牛膝100份、桂枝100份、威灵仙100份和老鹳草100份,加水煎煮2次,每次加水量为药材总重量的8倍,每次提取时间为3小时、2小时,合并煎液,滤过,滤液减压浓缩成65℃下相对密度为1.10的清膏;
(2)取清膏置入填充有D101大孔树脂的层析柱柱顶,清膏的质量为D101大孔树脂的5倍,用体积分数为65%乙醇进行洗脱,收集清膏体积4倍量的洗脱液,回收乙醇,继续浓缩成65℃下相对密度为1.30的浸膏;
(3)将海藻酸钠置于配料锅中,加水并在80℃下加热使海藻酸钠溶解,得质量分数为20%海藻酸钠溶液,再加入与海藻酸钠等质量的浸膏,以1500rpm的转速搅拌12min使浸膏充分混溶于海藻酸钠溶液中,制成水相;取液体石蜡置于配料锅中,再加入聚山梨酯80,加热至80℃,混匀,制成油相,所述浸膏、液体石蜡、聚山梨酯的质量比为1:1.2:6;
(4)控制油相的温度为75℃,搅拌,将所述水相缓慢加入油相中,以1500rpm的速度搅拌10min,制成混悬液;混悬液在2分钟内迅速降温至20℃后再加入占混悬液总体积3%的异丙醇,静置24h,得静置液;取静置液过滤,分离固液相,固体物在70℃下真空干燥12小时,得含水率为5.0%的微囊,即得所述治疗关节疼痛、腰腿酸痛制剂的活性成分。
实施例2
一种治疗关节疼痛、腰腿酸痛制剂的活性成分的制备方法,包括以下步骤:
(1)分别取处方量的制川乌100份、制草乌100份、防已100份、防风100份、续断100份、牛膝100份、桂枝100份、威灵仙100份和老鹳草100份,加水煎煮3次,每次加水量为药材总重量的8倍、7倍、6倍,每次提取时间为3小时、2小时、2小时,合并煎液,滤过,滤液减压浓缩成65℃下相对密度为1.12的清膏;
(2)取清膏置入填充有D101大孔树脂的层析柱柱顶,清膏的质量为D101大孔树脂的5倍,用体积分数为60%乙醇进行洗脱,收集清膏体积4倍量的洗脱液,回收乙醇,继续浓缩成65℃下相对密度为1.32的浸膏;
(3)将海藻酸钠置于配料锅中,加水并在84℃下加热使海藻酸钠溶解,得质量分数为20%海藻酸钠溶液,再加入与海藻酸钠等质量的浸膏,以1700rpm的转速搅拌7min使浸膏充分混溶于海藻酸钠溶液中,制成水相;取液体石蜡置于配料锅中,再加入聚山梨酯80,加热至86℃,混匀,制成油相,所述浸膏、液体石蜡、聚山梨酯的质量比为1:1.4:7;
(4)控制油相的温度为77℃,搅拌,将所述水相缓慢加入油相中,以1800rpm的速度搅拌8min,制成混悬液;混悬液在2分钟内迅速降温至25℃后再加入占混悬液总体积4%的异丙醇,静置21h,得静置液;取静置液过滤,分离固液相,固体物在65℃下真空干燥11小时,得含水率为5.3%的微囊,即得所述治疗关节疼痛、腰腿酸痛制剂的活性成分。
实施例3
一种治疗关节疼痛、腰腿酸痛制剂的活性成分的制备方法,包括以下步骤:
(1)分别取处方量的制川乌100份、制草乌100份、防已100份、防风100份、续断100份、牛膝100份、桂枝100份、威灵仙100份和老鹳草100份,加水煎煮2次,每次加水量为药材总重量的7倍,每次提取时间为3小时、2小时,合并煎液,滤过,滤液减压浓缩成65℃下相对密度为1.20的清膏;
(2)取清膏置入填充有D101大孔树脂的层析柱柱顶,清膏的质量为D101大孔树脂的5倍,用体积分数为55%乙醇进行洗脱,收集清膏体积4倍量的洗脱液,回收乙醇,继续浓缩成65℃下相对密度为1.35的浸膏;
(3)将海藻酸钠置于配料锅中,加水并在90℃下加热使海藻酸钠溶解,得质量分数为20%海藻酸钠溶液,再加入与海藻酸钠等质量的浸膏,以2000rpm的转速搅拌5min使浸膏充分混溶于海藻酸钠溶液中,制成水相;取液体石蜡置于配料锅中,再加入聚山梨酯80,加热至90℃,混匀,制成油相,所述浸膏、液体石蜡、聚山梨酯的质量比为1:1.2:6.2;
(4)控制油相的温度为80℃,搅拌,将所述水相缓慢加入油相中,以2000rpm的速度搅拌5min,制成混悬液;混悬液在1.5分钟内迅速降温至30℃后再加入占混悬液总体积5%的异丙醇,静置18h,得静置液;取静置液过滤,分离固液相,固体物在60℃下真空干燥10小时,得含水率为6.0%的微囊,即得所述治疗关节疼痛、腰腿酸痛制剂的活性成分。
实施例4
一种治疗关节疼痛、腰腿酸痛的制剂,其制备方法如下:
取实施例1的微囊100份,再取羟丙基甲基纤维素25份,乳糖9份,微晶纤维素35份,十二烷基硫酸钠8份,聚乙烯比咯烷酮8份、微粉硅胶1份,混匀,压制成0.30g/片的素片,薄膜包衣,即得所述治疗关节疼痛、腰腿酸痛的制剂。
实施例5
一种治疗关节疼痛、腰腿酸痛的制剂,其制备方法如下:
取实施例2的微囊100份,再取羟丙基甲基纤维素28份,乳糖9.5份,微晶纤维素37份,十二烷基硫酸钠9份,聚乙烯比咯烷酮9份、微粉硅胶1.5份,混匀,压制成0.33g/片的素片,薄膜包衣,即得所述治疗关节疼痛、腰腿酸痛的制剂。
实施例6
一种治疗关节疼痛、腰腿酸痛的制剂,其制备方法如下:
取实施例3的微囊100份,再取羟丙基甲基纤维素30份,乳糖10份,微晶纤维素40份,十二烷基硫酸钠10份,聚乙烯比咯烷酮10份、微粉硅胶2份,混匀,压制成0.35g/片的素片,薄膜包衣,即得所述治疗关节疼痛、腰腿酸痛的制剂。
制剂质量评价
1、测定浸膏的收膏率及含量
取本发明实施例1-3及说明书背景技术中所述的风湿灵片原方法提取浸膏进行比对,采用高效液相色谱法检测。以粉防己碱为对照品,用甲醇稀释至0.05mg/ml。取实施例1-3的风湿灵浸膏0.1g,加入25ml甲醇,超声处理30min,过滤,取滤液。检测波长:280nm,计算包封率,结果见表1。
浸膏 | 收膏率(%) | 含量(mg/g) |
原法浸膏 | 30.2 | 30.18 |
实施例1 | 8.98 | 107.15 |
实施例2 | 8.93 | 106.89 |
实施例3 | 8.86 | 106.91 |
表1浸膏的收膏率及含量情况
从表中可以看出,本发明实施例1-3的浸膏的收膏率为8.89%,远小于原提取工艺的浸膏收膏率,然而本发明实施例浸膏中的防己碱平均含量为106.98,比原工艺提高了254.47%,大大提高了药材的利用率。
2.测定微囊的载药量
分别称取实施例1-3的微囊各5g,加50ml水超声30min,加入乙醚进行萃取3次,每次50mL,滤过,合并乙醚层,放在单口瓶旋蒸,然后放在105℃的烘干箱烘干,把烘干的单口瓶放在真空干燥器中,冷却至室温,称重,计算单口瓶中微囊里面风湿灵浸膏的重量,根据公式:载药量(%)=微囊里面浸膏重量/微囊重量×100%,计算载药量,计算结果见表2。
实施例 | 载药量(%) |
1 | 47.06 |
2 | 48.09 |
3 | 49.01 |
表2实施例4-6微囊的载药量情况
3、体外溶出度
采用中国药典2015年版“溶出度与释放度测定法”第一法(通则0931),取实施例4-6制备的样品以及市售风湿灵片(糖衣片)进行检测,样品含量测定采用采用紫外-可见分光光度法,以汉防己甲素为对照品,在282nm处测定吸光度,然后计算溶出度,结果见表3。
表3溶出度测定情况
从表3可以看出,本发明的长效新制剂比普通制法制成的市售糖衣片药物释放相对平稳、半衰期长,表明其生物利用度高,同时其不良反应相对较小。
4、药物释放曲线
由附图1的释放曲线可见,市售风湿灵片(糖衣片)在2小时平均累积释放度即达到80%以上,而本发明所制得的长效新制剂在16小时其平均累积释放度才达到60%以上,表明其具有较好的缓释效果。
5、水分测定
取本发明实施例4-6及市售风湿灵片,置稳定性试验箱,于温度40℃±2℃、相对湿度75%±5%条件下进行6个月加速试验,按照《中国药典》2015年版一部附录水分项下检验,详见表4。
样品名称 | 0月 | 1月 | 2月 | 3月 | 6月 |
实施例4 | 4.1% | 4.1% | 4.2% | 4.2% | 4.2% |
实施例5 | 4.0% | 4.2% | 4.2% | 4.3% | 4.3% |
实施例6 | 4.3% | 4.3% | 4.5% | 4.7% | 4.8% |
市售风湿灵片(糖衣片) | 6.0% | 6.7% | 6.7% | 8.0% | 8.9% |
表4水分测定结果表
试验结果表明:本发明制备的片剂(薄膜衣片),与市售的风湿灵片(糖衣片)相比,药物的引湿性明显降低,解决了药物在生产及贮存过程极易受潮变质的问题。
6、含量测定
采用中国药典2015年版“紫外-可见分光光度法”及高效液相色谱法,分别检测样品的汉防己甲素及乌头总碱含量,取实施例4-6制备的样品以及市售风湿灵片(糖衣片)进行检测,结果见表5。
样品名称 | 汉防己甲素(mg/片) | 乌头总碱(ug/片) |
实施例4 | 3.2 | 15 |
实施例5 | 3.3 | 14 |
实施例6 | 3.5 | 14 |
市售风湿灵片 | 0.65 | 22 |
表5含量测定结果表
试验结果表明:本发明制备的片剂(薄膜衣片),与市售的风湿灵片(糖衣片)相比,乌头总碱的含量较高明显降低,提示其毒副作用明显低于市售风湿灵片(糖衣片)。
Claims (8)
1.一种治疗关节疼痛、腰腿酸痛制剂的制备方法,其特征在于,包括以下步骤:
(1)分别取处方量的制川乌100份、制草乌100份、防已100份、防风100份、续断100份、牛膝100份、桂枝100份、威灵仙100份和老鹳草100份,加水煎煮2-3次,每次加水量为药材总重量的6-8倍、提取时间为2-3小时,合并煎液,滤过,滤液减压浓缩成65℃下相对密度为1.10-1.20的清膏;
(2)取清膏置入填充有D101大孔树脂的层析柱柱顶,用体积分数为55-65%乙醇进行洗脱,收集清膏体积4倍量的洗脱液,回收乙醇,继续浓缩成65℃下相对密度为1.30-1.35的浸膏;
(3)将海藻酸钠置于配料锅中,加水并在80-90℃下加热使海藻酸钠溶解,得质量分数为20%海藻酸钠溶液,再加入浸膏,搅拌使浸膏充分混溶于海藻酸钠溶液中,制成水相;取液体石蜡置于配料锅中,再加入聚山梨酯80,加热至80-90℃,混匀,制成油相;
(4)控制油相的温度为75-80℃,搅拌,将所述水相缓慢加入油相中,继续搅拌10min,制成混悬液;混悬液降温至20-30℃后再加入占混悬液总体积3-5%的异丙醇,静置18-24h,得静置液;取静置液过滤,分离固液相,固体物真空干燥,得微囊;
(5)按照以下重量份数称取各原料:微囊100份、羟丙基甲基纤维素25-30份、乳糖9-10份、微晶纤维素35-40份、十二烷基硫酸钠8-10份、聚乙烯比咯烷酮8-10份、微粉硅胶1份,混匀,压制成素片,薄膜包衣,即得。
2.根据权利要求1所述一种治疗关节疼痛、腰腿酸痛制剂的制备方法,其特征在于,所述微囊的水分≤6%。
3.根据权利要求1所述一种治疗关节疼痛、腰腿酸痛制剂的制备方法,其特征在于,所述步骤(3)、(4)的搅拌速度为1500-2000rpm。
4.根据权利要求1所述一种治疗关节疼痛、腰腿酸痛制剂的制备方法,其特征在于,所述步骤(4)的真空干燥温度为60℃-70℃,时间为10-12小时。
5.根据权利要求1所述一种治疗关节疼痛、腰腿酸痛制剂的制备方法,其特征在于,所述步骤(5)的片重为0.30-0.35g。
6.根据权利要求1所述一种治疗关节疼痛、腰腿酸痛制剂的制备方法,其特征在于,所述步骤(2)的清膏与D101大孔树脂的质量比为5:1。
7.根据权利要求1所述一种治疗关节疼痛、腰腿酸痛制剂的制备方法,其特征在于,所述步骤(3)中浸膏和海藻酸钠的质量比为1:1;浸膏、液体石蜡、聚山梨酯的质量比为1:1.2:6。
8.一种如权利要求1所述一种治疗关节疼痛、腰腿酸痛制剂的制备方法制成的片剂,其特征在于,所述片剂的含量范围为:乌头总碱≦20ug/片、汉防己甲素≥3.0mg/片。
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