CN116077417A - 一种胃滞留片剂及制备方法 - Google Patents
一种胃滞留片剂及制备方法 Download PDFInfo
- Publication number
- CN116077417A CN116077417A CN202211702031.2A CN202211702031A CN116077417A CN 116077417 A CN116077417 A CN 116077417A CN 202211702031 A CN202211702031 A CN 202211702031A CN 116077417 A CN116077417 A CN 116077417A
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- Prior art keywords
- polysaccharide
- tablet
- hypromellose
- hydrophilic gel
- gel material
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
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Abstract
本发明公开了一种胃滞留片剂及其制备方法,包括功效成分、填充剂、亲水凝胶材料和起泡剂,其中所述亲水凝胶材料包含岩藻多糖和羟丙甲纤维素。本发明通过辅料的筛选及优化,制备得到的胃滞留片剂能够实现在胃部快速起漂并滞留,使功效成分能持续在胃部释放,并3‑4h内在胃部释放完全,与胃完全排空的周期相适应,保证了在抑制和粘附的幽门螺旋杆菌的同时及时将幽门螺旋杆菌排出,且可以大大提升压片后益生菌的存活率,保持了更多的活性益生菌能够在胃部发挥作用。
Description
技术领域
本发明涉及医药和保健食品技术领域,具体涉及一种胃滞留片剂及其制备方法。
背景技术
慢性胃病常指慢性胃炎(浅表性胃炎、萎缩性胃炎)和溃疡病(胃溃疡和十二指肠溃疡)。胃镜普查证实,我国人群中慢性胃炎的发病率高达60%以上,溃疡病的发病率为10%左右。而慢性胃病的病因尚未完全阐明,长期无理想的防治方法。目前有较高认可度的是胃黏膜中一种叫幽门螺杆菌(Hp)的细菌与慢性胃病发病有关,即Hp是引发多种慢性胃病的重要病因之一。Hp是一种螺旋形、微需氧的革兰氏阴性菌,在大气或绝对厌氧环境下不能生长,但进入胃部及十二指肠内却能很好地生长繁殖,并引起局部疾病。当Hp经口进入胃内时,部分可被胃酸杀灭,部分附着于胃窦部黏液层,依靠其鞭毛摆动穿过黏液层,定植于黏液层与胃窦黏膜上皮细胞表面,一般不侵入胃腺和固有层内,一方面避免了胃酸的杀菌作用,另一方面难以被机体的免疫机能清除。大多数Hp感染者并无明显症状,或多有非特异性症状,如中上腹不适、饱胀、钝痛,以及食欲减退、嗳气、反酸、恶心等消化不良的症状,同时体征并不明显。值得注意的是,由于Hp感染不一定能引发明显疾病,易被忽视,一旦感染应及时予以治疗。
抗生素治疗,例如四联疗法【质子泵抑制剂(如奥美拉唑等)+铋剂或胃黏膜保护剂+两种抗生素】,是目前常规的Hp根除的治疗方案。然而随着Hp抗生素耐药性在全球范围内逐渐增强,抗生素根除治疗的成功率在不断下降;同时,抗生素治疗对于肠道健康微生态的潜在不良影响也逐渐引起了广泛关注。为了应对这些存在的问题和挑战,研究者开始寻找其它辅助和替代疗法,例如益生菌类、多糖类成分或者胃部缓释、悬浮剂型等。
但是,市面上上市的护胃产品主要集中在抗幽门螺旋杆菌和中药养胃上,应用剂型主要为胶囊和粉剂。然而,该类产品通常具有溶解快,在胃部的排空受进食影响的问题。空腹服用时15min到30min即被排空至肠道,进食后服用排空时间稍微较长,但其在胃部排空的时间不定,根据人进食物质成分的不同,排空时间短则30min,最长不超过4h,一般小于2h。然而,对于胃部用药而言,胃部的停落时间影响对疗效的影响较大。停落时间短,则与胃上皮细胞接触时间短,发挥疗效的时间则短,反之,则发挥疗效时间长。
胃部滞留给药系统能有效延长药物在胃液中滞留时间,改善吸收,提高生物利用度,目前胃滞留给药系统的类型主要有:密度型、漂浮型、生物黏附型、展开溶胀型、超多孔水性凝胶型及磁导向型等胃滞留给药系统。但是目前的胃部滞留给药系统都是应用于小分子化合物的长时间滞留,滞留时间超过七八个小时,甚至二十多个小时。但是这种用于小分子药物的胃滞留给药系统溶解性差,分子间结合紧密,对于蛋白、多糖、益生菌等大分子物质的溶解释放发挥功效造成了障碍,过长的滞留时间也不利于幽门螺旋杆菌的清除排出。
因此,急需一种可稳定提供胃部停留时间,能够有效保持含多糖、益生菌释放的胃滞留产品。
发明内容
为了克服现有技术的缺点与不足,本发明的首要目的在于提供一种胃滞留片剂,该产品实现了其在胃部快速起漂、在胃液中滞留时间控制在3-4h、与胃完全排空的周期相适应,保证了在抑制和粘附的幽门螺旋杆菌的同时及时将幽门螺旋杆菌排出,且能大大提升压片后益生菌的存活率,保持更多的活性益生菌能够在胃部发挥作用。
本发明是通过以下技术方案实现的:
一种胃滞留片剂,包括功效成分、填充剂、亲水凝胶材料和起泡剂,其中所述亲水凝胶材料包含岩藻多糖和羟丙甲纤维素。
作为优选,本发明所述的胃滞留片剂,按重量百分比计,各组分的用量为:
功效成分10-30%、填充剂10-30%、亲水凝胶材料30-50%、起泡剂4-10%。
本发明通过筛选意外的发现采用岩藻多糖与羟丙甲纤维素(HPMC)作为亲水凝胶材料能够提升益生菌的释放度,与起泡剂组合可以使产品在胃部迅速起漂并滞留,使功效成分能持续在胃部释放,并3-4h内在胃部释放完全。
进一步研究表明,羟丙甲纤维素与岩藻多糖的比例影响本发明的技术效果,当羟丙甲纤维素含量太低起漂时间长,释放持续时间短,羟丙甲纤维素含量太高,释放度不足,合适的岩藻多糖与羟丙甲纤维素比例,能够满足快速漂浮、控释3-4h的需求。因此,作为优选,所述亲水凝胶材料中岩藻多糖和羟丙甲纤维素的重量比为1:1.5-1:4,其中羟丙甲纤维素的用量不低于25%。
作为优选,所述羟丙甲纤维素为HPMCK100LV,其中甲氧基含量19-24%,羟丙氧基含量4-12%,羟丙甲纤维素2%水溶液的粘度为70-150mpa.s。
作为优选,所述岩藻多糖2%水溶液的粘度为1-15 mpa.s。本发明采用低粘度的岩藻多糖
与羟丙甲纤维素组合应用,可以平衡并稳定释放速度。
进一步的,作为优选,本发明采用岩藻多糖与羟丙甲纤维素作为亲水凝胶材料,与糖醇
类填充剂之间可以形成多糖纤维复合体网格,该多糖纤维复合体网格具有包裹作用以及缓冲作用,可以提升益生菌在压片生产加工过程中的活性,降低压力以及起泡剂中的酸碱试剂对于益生菌活性的不利影响,大大提升了压片后益生菌的存活率。
作为优选,所述功效成分为益生菌、植物多糖或其组合。其中益生菌包括罗伊氏乳杆
菌、植物乳杆菌、副干酪乳杆菌等食品可用的益生菌株;所述植物多糖选自猴头菇多糖、茯苓多糖、太子参多糖、桑黄多糖、银耳多糖、香菇多糖、当归多糖、黄芪多糖等养胃护胃抗炎多糖中的一种或几种。
作为优选,所述填充剂为一水乳糖、山梨糖醇、微晶纤维素、D-甘露糖醇中的一种或几
种的组合,更优选为D50为100-200um的D-甘露糖醇。特定的D-甘露糖醇(D50为100-200um)的使用能够进一步的提升压片过程中的益生菌的活性。
作为优选,所述起泡剂为碱与酸的组合物,当然考虑胃酸环境,也可以只单用碱。其中碱
可选择碳酸氢钠、碳酸钠、碳酸钙或碳酸镁中的一种或多种;酸可以选择柠檬酸、酒石酸;
作为优选,所述起泡剂为碳酸氢钠与无水柠檬酸的组合物。
作为优选,本发明胃滞留片剂还包括润滑剂1-4%,所述润滑剂为磷酸三钙、二氧化硅、
聚乙二醇6000或硬脂酸镁中的一种或几种的组合。
本发明还提供了上述胃滞留片剂的制备方法,包括如下方法:
方法一(直接压片法):
(1)将功效成分、填充剂、亲水凝胶材料、起泡剂加入混合机混合均匀,再加入润滑剂混合;
(2)将上述混合物放入压片机压片,控制硬度6-14 kg/cm2,铝塑包装。
或方法二(湿法制粒后压片法):
(1)将填充剂、亲水凝胶材料制粒;
(2)将功效成分、制粒颗粒、起泡剂混合均匀,再加入润滑剂混合;
(3)将上述混合物放入压片机压片,控制硬度6-14 kg/cm2,铝塑包装。
本发明与现有技术相比,具有如下有益效果:
本发明功效成分中益生菌具有抗幽、清幽效果,植物多糖具有养胃、护胃效果,通过辅料的筛选及优化,制备得到的胃滞留片剂能够实现在胃部快速起漂并滞留,使功效成分能持续在胃部释放发挥作用,并3-4h内在胃部释放完全,与胃完全排空的周期相适应,保证了在抑制和粘附的幽门螺旋杆菌的同时及时将幽门螺旋杆菌排出,且可以大大提升压片后益生菌的存活率,保持了更多的活性益生菌能够在胃部发挥作用。相对普通片剂、胶囊口服后被胃部排空,转移至肠道,易受饮食和胃排空影响的情况,本发明的胃滞留片剂不受胃排空的影响,保证产品在胃部持续稳定的释放,维持疗效。
具体实施方式
下面通过具体实施方式来进一步说明本发明,以下实施例为本发明较佳的实施方式,但本发明的实施方式并不受下述实施例的限制。
本发明实施例和对比例所用原料或辅料均可由市场购得,其中HPMCK100LV 来自美国亚什兰公司,货号: Benecel K100LV;岩藻多糖来自青岛明月海藻岩藻多糖生物科技有限公司,货号 BMSFu-Hp;D-甘露糖醇(D50为100-200um)来自默克股份两合公司,产品编号100419。
实施例1-8:
以重量占比计,本实施例胃滞留片剂配方如下表1:
表1:胃滞留片实施例配方(重量百分比)
物质 | 实施例1 | 实施例2 | 实施例3 | 实施例4 | 实施例5 | 实施例6 | 实施例7 | 实施例8 |
益生菌 | 18 | 18 | 18 | 18 | 15 | 12 | 18 | 18 |
猴头菇多糖 | 5 | 5 | 5 | 5 | 10 | 14 | 5 | 5 |
岩藻多糖 | 13 | 10 | 8 | 8.5 | 8.5 | 8.5 | 8.5 | 8.5 |
HPMCK100LV | 26 | 30 | 32 | 31.5 | 31.5 | 31.5 | 31.5 | 31.5 |
碳酸氢钠 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 |
无水柠檬酸 | 3.7 | 3.7 | 3.7 | 3.7 | 3.7 | 3.7 | 3.7 | 3.7 |
D-甘露糖醇(D50为100-200um) | / | / | / | / | / | / | 6 | 10 |
山梨糖醇 | 27.05 | / | 7 | 7 | 11.05 | 13 | 7 | 10 |
一水乳糖 | / | 26.05 | 19.05 | 19.05 | 13 | 10.05 | 13.05 | 5.3 |
磷酸三钙 | 0.75 | / | / | 0.75 | 0.75 | / | 0.75 | 0.75 |
二氧化硅 | / | 0.75 | 0.75 | / | / | 0.75 | / | 0.75 |
硬脂酸镁 | 1.5 | 1.5 | 1.5 | 1.5 | 1.5 | 1.5 | 1.5 | 1.5 |
起漂时间 | 2-5min | 2-4min | 1-3min | 1-3min | 1-3min | 1-3min | 1-3min | 1-3min |
压片后益生菌存活率 | 47.20% | 45.10% | 43.40% | 44.30% | 43.90% | 44.20% | 59.40% | 63.70% |
释放持续时间 | 3h | 3h | 4h | 4h | 4h | 4h | 4h | 4h |
终点释放度 | 100.0% | 100.0% | 100.0% | 100.0% | 100.0% | 100.0% | 100.0% | 100.0% |
制备工艺:
(1)将填充剂过20目筛,起泡剂过40目筛;
(2)将益生菌、猴头菇多糖、岩藻多糖、HPMCK100LV、起泡剂、填充剂混合均匀,再加入润滑剂混合均匀,得总混料;
(3)压片、包装:将总混料加入压片机压片,控制硬度6-14 kg/cm2,铝塑包装。
评价测定方法:
评价测定指标为pH1.0溶液中起漂时间、压片后益生菌存活率、释放持续时间、终点释放度。其中起漂时间、释放持续时间,采用记时法测定;压片后益生菌存活率,参照GB4789.35-2016方法进行测定;终点释放度,采用凯氏定氮法,以蛋白质计进行测定。
具体的:
pH1.0溶液中起漂时间:取2片,放入装250mlpH1.0溶液的烧杯中,计时,至片漂浮于液面,连续测定3次。
释放持续时间:100%释放量的时间或取样终点时间(未达100%释放时)。
压片后益生菌存活率:分别取总混粉和压制片,参照GB4789.35-2016方法检验其乳酸菌总数,存活率=(总混粉乳酸菌总数-片乳酸菌总数)/总混粉乳酸菌总数。
释放度:取本品,照中国药典2020年版四部0931溶出度与释放度测定法第一法测定,以pH1.0溶液为溶剂,转速为每分钟100转,依法操作,分别于30min、1h、2h、3h、4h取样测定蛋白质含量,计算释放度。
终点释放度:100%或取样终点的释放度(未达100%释放时)。
试验例1:亲水凝胶材料对产品性能的影响
选择小分子量壳聚糖(分子量小于等于3000)、海藻酸钠、岩藻多糖、HPMCK100LV、HPMCK4M作为亲水凝胶评价材料,对不同组方制得的样品进行评价,配方和评价情况如表2。
表2:亲水凝胶材料对产品性能的影响
物质 | 组方1 | 组方2 | 组方3 | 组方4 | 组方5 | 组方6 | 组方7 | 组方8 |
益生菌 | 18 | 18 | 18 | 18 | 18 | 18 | 18 | 18 |
猴头菇多糖 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 |
岩藻多糖 | / | 8.5 | / | / | 8.5 | / | / | 8.5 |
海藻酸钠 | / | / | / | / | / | 8.5 | / | / |
小分子量壳聚糖(分子量小于等于3000) | / | / | / | / | / | / | 8.5 | / |
HPMCK100LV | / | / | 31.5 | / | / | 31.5 | 31.5 | 31.5 |
HPMCK4M | / | / | / | 31.5 | 31.5 | / | / | / |
碳酸氢钠 | / | 5 | 5 | 5 | 5 | 5 | 5 | 5 |
无水柠檬酸 | / | 3.7 | 3.7 | 3.7 | 3.7 | 3.7 | 3.7 | 3.7 |
山梨糖醇 | 37.75 | 30.55 | 17.55 | 17.55 | 13.05 | 13.05 | 13.05 | 13.05 |
一水乳糖 | 37 | 27 | 17 | 17 | 13 | 13 | 13 | 13 |
磷酸三钙 | 0.75 | 0.75 | 0.75 | 0.75 | 0.75 | 0.75 | 0.75 | 0.75 |
硬脂酸镁 | 1.5 | 1.5 | 1.5 | 1.5 | 1.5 | 1.5 | 1.5 | 1.5 |
起漂时间 | 不起漂 | 不起漂 | 2-5min | 1-3min | 2-4min | 2-4min | 5-8min | 1-3min |
压片后益生菌存活率 | 20.70% | 34.60% | 23.40% | 19.90% | 35.50% | 22.10% | 24.70% | 44.10% |
释放持续时间 | 30min | 60min | 4h | 4h | 4h | 4h | 4h | 4h |
终点释放度 | 100.0% | 100.0% | 76.1% | 13.6% | 19.3% | 38.5% | 58.4% | 100.0% |
由上表结果看出,组方1中未添加亲水凝胶材料,在酸性溶液不漂浮,快速崩解释放,且压片后益生菌存活率低。组方2-4考察了单一亲水凝胶材料的情况,以组方2同其他组方进行比较发现单纯使用岩藻多糖不起漂,释放快,但是相比于未使用凝胶材料的组方1释放时间有所延长;相比于不使用岩藻多糖的组方,岩藻多糖的使用显著提高了益生菌存活率。从组方3可以看出羟丙甲纤维素K100LV漂浮快,但是释放较慢,在4h的释放度未到达100%,其对于益生菌的存活仅有轻微的保护作用。从组方4可以看出羟丙甲纤维素K4M漂浮快,但释放非常慢,对益生菌也基本没有保护作用。
进一步的,本发明基于组方2-4的情况,选择以羟丙甲纤维素(HPMC)为基础,搭配其它亲水凝胶材料进行组合。组方5显示,HPMC K4M与岩藻多糖组合,虽然较单纯的使用HPMC K4M在终点释放度和益生菌活性上有所改善,但是释放依然很慢;从组方6显示,选择海藻酸钠与HPMC K100LV组合释放度较单纯使用HPMC K100LV反而会严重延缓释放度,同时对益生菌的保护作用有限。组方7显示小分子量壳聚糖与HPMC K100LV组合在一定程度上也会延缓释放度,同时对益生菌的保护作用有限。由组方8结果显示,使用岩藻多糖和HPMCK100LV组合,产品在胃部迅速起漂并滞留,岩藻多糖能够提升益生菌的释放度,盐藻多糖与HPMC K100LV能大幅提升压片后益生菌的存活率(P<0.05),即在释放度和益生菌保护方面两者都起到了协同促进作用。因此,本发明选择岩藻多糖和HPMC K100LV作为亲水凝胶材料。
试验例2:岩藻多糖与羟丙甲纤维素的用量比例对产品性能的影响
选择岩藻多糖和羟丙甲纤维素K100LV作为亲水凝胶材料,调整岩藻多糖与羟丙甲纤维素的用量比例,具体配方如表3所示,对不同组方制得的样品进行评价,评价结果见表3。
表3:
物质 | 组方9 | 组方10 | 组方11 | 组方12 | 组方13 | 组方14 |
益生菌 | 18 | 18 | 18 | 18 | 18 | 18 |
猴头菇多糖 | 5 | 5 | 5 | 5 | 5 | 5 |
岩藻多糖 | 13.3 | 10 | 8 | 8.5 | 15.5 | 8.5 |
HPMCK100LV | 26.7 | 30 | 32 | 31.5 | 20 | 45 |
碳酸氢钠 | 5 | 5 | 5 | 5 | 5 | 5 |
无水柠檬酸 | 3.7 | 3.7 | 3.7 | 3.7 | 3.7 | 3.7 |
山梨糖醇 | 7 | 7 | 7 | 7 | 15.55 | 12.55 |
一水乳糖 | 19.05 | 19.05 | 19.05 | 19.05 | 15 | / |
磷酸三钙 | 0.75 | / | / | 0.75 | 0.75 | 0.75 |
二氧化硅 | / | 0.75 | 0.75 | / | / | / |
硬脂酸镁 | 1.5 | 1.5 | 1.5 | 1.5 | 1.5 | 1.5 |
起漂时间 | 2-5min | 2-4min | 1-3min | 1-3min | 25-30min | 1-3min |
压片后益生菌存活率 | 47.40% | 45.10% | 43.40% | 43.30% | 46.20% | 43.90% |
释放持续时间 | 3h | 3h | 4h | 4h | 2h | 4h |
终点释放度 | 100.0% | 100.0% | 100.0% | 100.0% | 100.0% | 64.8% |
由上表3结果看出,组方13中,当岩藻多糖占比较高,且HPMC K100LV含量较低时,起漂时间长,释放持续时间短。在测试中还发现,HPMC K100LV的含量低于25%时,起漂时间不能满足快速起漂的要求。组方14中,岩藻多糖占比较低,同时羟丙甲纤维素K100LV含量太高,释放度不足。因此,本发明优选岩藻多糖和羟丙甲纤维素的重量比为1:1.5-1:4,且HPMCK100LV的含量不低于25%。
试验例3:D-甘露糖醇能够提高益生菌的存活率
选择D-甘露糖醇(D50为100-200um)作为填充剂,配方如表4,对不同组方制得的样品进行评价,评价结果见表4。
表4:D-甘露糖醇的添加对产品性能的影响
物质 | 组方15 | 组方16 | 组方17 | 组方18 | 组方19 | 组方20 | 组方21 | 组方22 |
益生菌 | 18 | 18 | 18 | 18 | 18 | 18 | 18 | 18 |
猴头菇多糖 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 |
岩藻多糖 | 8.5 | 8.5 | 10 | / | / | / | / | / |
HPMCK100LV | 31.5 | 31.5 | 30 | 31.5 | 31.5 | 31.5 | 31.5 | 31.5 |
碳酸氢钠 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 |
无水柠檬酸 | 3.7 | 3.7 | 3.7 | 3.7 | 3.7 | 3.7 | 3.7 | 3.7 |
D-甘露糖醇(D50为100-200um) | 10 | 6 | 6 | 6 | 10 | 14.5 | 16 | 18.5 |
山梨糖醇 | 7 | 7 | 7 | 13 | 10.5 | 7 | 6 | 7 |
一水乳糖 | 9.05 | 12.3 | 13.05 | 14.8 | 13.3 | 13.05 | 12.55 | 9.05 |
磷酸三钙 | 0.75 | 0.75 | / | 0.75 | 0.75 | 0.75 | 0.75 | 0.75 |
二氧化硅 | / | 0.75 | 0.75 | 0.75 | 0.75 | / | / | / |
硬脂酸镁 | 1.5 | 1.5 | 1.5 | 1.5 | 1.5 | 1.5 | 1.5 | 1.5 |
起漂时间 | 1-3min | 1-3min | 2-4min | 1-3min | 1-3min | 1-3min | 1-3min | 1-3min |
压片后益生菌存活率 | 63.50% | 59.5% | 60.20% | 39.30% | 46.30% | 51.80% | 52.70% | 55.90% |
释放持续时间 | 4h | 4h | 4h | 4h | 4h | 4h | 4h | 4h |
终点释放度 | 100.00% | 100.00% | 100.00% | 74.80% | 72.60% | 71.50% | 68.40% | 68.40% |
由上表4结果看出,D-甘露糖醇(D50为100-200um)的加入能够提升益生菌的存活能力,D-甘露糖醇的使用不会影响胃滞留片的漂浮和滞留能力,并且在岩藻多糖的存在下,岩澡多糖与D-甘露糖醇对于压片中益生菌的保护效果进一步的提升,相较于单独使用岩藻多糖或D-甘露聚糖,两者的共同使用起到了协同增效的作用(P<0.05),可以减少昂贵的D-甘露糖醇的使用,降低生产中的成本。
以上所述仅是本发明的优选实施方式,应当指出,对于本技术领域的普通技术人员来说,在不脱离本发明原理的前提下,还可以做出若干改进和润饰,这些改进和润饰也应视为本发明的保护范围。
Claims (10)
1.一种胃滞留片剂,其特征在于,包括功效成分、填充剂、亲水凝胶材料和起泡剂,其中所述亲水凝胶材料包含岩藻多糖和羟丙甲纤维素。
2.根据权利要求1所述的胃滞留片剂,其特征在于,按重量百分比计,各组分的用量为:
功效成分10-30%、填充剂10-30%、亲水凝胶材料30-50%、起泡剂4-10%。
3.根据权利要求1或2所述的胃滞留片剂,其特征在于,所述亲水凝胶材料中岩藻多糖和羟丙甲纤维素的重量比为1:1.5-1:4,其中羟丙甲纤维素用量不低于25%。
4.根据权利要求 1或2所述的胃滞留片剂,其特征在于,所述羟丙甲纤维素为HPMCK100LV,其中甲氧基含量19-24%,羟丙氧基含量4-12%;所述羟丙甲纤维素2%水溶液的粘度为70-150mpa.s。
5.根据权利要求1或2所述的胃滞留片剂,其特征在于,所述岩藻多糖2%水溶液的粘度为1-15 mpa.s。
6.根据权利要求1或2所述的胃滞留片剂,其特征在于,所述功效成分为益生菌、植物多糖或其组合;所述益生菌包括罗伊氏乳杆菌、植物乳杆菌或副干酪乳杆菌中的一种或几种;所述植物多糖选自猴头菇多糖、茯苓多糖、太子参多糖、桑黄多糖、银耳多糖、香菇多糖、当归多糖、黄芪多糖中的一种或几种。
7.根据权利要求1或2所述的胃滞留片剂,其特征在于,所述填充剂为一水乳糖、山梨糖醇、微晶纤维素、D-甘露糖醇中的一种或几种的组合,优选D50为100-200um的D-甘露糖醇。
8.根据权利要求1或2所述的胃滞留片剂,其特征在于,所述起泡剂为酸和碱的组合物,优选为碳酸氢钠和无水柠檬酸的组合物。
9.根据权利要求1或2所述的胃滞留片剂,其特征在于,还包括润滑剂1-4%,所述润滑剂为磷酸三钙、二氧化硅、聚乙二醇6000或硬脂酸镁中的一种或几种的组合。
10.根据权利要求1-9任一项所述的胃滞留片剂的制备方法,其特征在于,包括如下方法:
方法一:
(1)将功效成分、填充剂、亲水凝胶材料、起泡剂加入混合机混合均匀,再加入润滑剂混合;
(2)将上述混合物放入压片机压片,控制硬度6-14 kg/cm2,铝塑包装;
或方法二:
(1)将填充剂、亲水凝胶材料制粒;
(2)将功效成分、制粒颗粒、起泡剂混合均匀,再加入润滑剂混合;
将上述混合物放入压片机压片,控制硬度6-14 kg/cm2,铝塑包装。
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