CN110292582A - 一种鞣花酸-蒙脱石泡腾剂及其制备方法 - Google Patents
一种鞣花酸-蒙脱石泡腾剂及其制备方法 Download PDFInfo
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- 229910052901 montmorillonite Inorganic materials 0.000 title claims abstract description 31
- 238000002360 preparation method Methods 0.000 title claims abstract description 20
- AFSDNFLWKVMVRB-UHFFFAOYSA-N Ellagic acid Chemical compound OC1=C(O)C(OC2=O)=C3C4=C2C=C(O)C(O)=C4OC(=O)C3=C1 AFSDNFLWKVMVRB-UHFFFAOYSA-N 0.000 claims abstract description 68
- ATJXMQHAMYVHRX-CPCISQLKSA-N Ellagic acid Natural products OC1=C(O)[C@H]2OC(=O)c3cc(O)c(O)c4OC(=O)C(=C1)[C@H]2c34 ATJXMQHAMYVHRX-CPCISQLKSA-N 0.000 claims abstract description 67
- 229920002079 Ellagic acid Polymers 0.000 claims abstract description 67
- 235000004132 ellagic acid Nutrition 0.000 claims abstract description 67
- 229960002852 ellagic acid Drugs 0.000 claims abstract description 67
- FAARLWTXUUQFSN-UHFFFAOYSA-N methylellagic acid Natural products O1C(=O)C2=CC(O)=C(O)C3=C2C2=C1C(OC)=C(O)C=C2C(=O)O3 FAARLWTXUUQFSN-UHFFFAOYSA-N 0.000 claims abstract description 67
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims abstract description 36
- 229920003081 Povidone K 30 Polymers 0.000 claims abstract description 29
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 26
- 239000007962 solid dispersion Substances 0.000 claims abstract description 25
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 22
- 239000002253 acid Substances 0.000 claims abstract description 12
- 239000003513 alkali Substances 0.000 claims abstract description 12
- 239000000945 filler Substances 0.000 claims abstract description 9
- 239000000314 lubricant Substances 0.000 claims abstract description 9
- 238000007873 sieving Methods 0.000 claims abstract description 8
- 239000003960 organic solvent Substances 0.000 claims abstract description 7
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims abstract description 7
- 239000011122 softwood Substances 0.000 claims abstract description 7
- 238000005303 weighing Methods 0.000 claims abstract description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 21
- GUJOJGAPFQRJSV-UHFFFAOYSA-N dialuminum;dioxosilane;oxygen(2-);hydrate Chemical compound O.[O-2].[O-2].[O-2].[Al+3].[Al+3].O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O GUJOJGAPFQRJSV-UHFFFAOYSA-N 0.000 claims description 14
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 10
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims description 7
- 235000015165 citric acid Nutrition 0.000 claims description 7
- 239000000203 mixture Substances 0.000 claims description 6
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 claims description 5
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 claims description 5
- 239000001630 malic acid Substances 0.000 claims description 5
- 235000011090 malic acid Nutrition 0.000 claims description 5
- 239000007787 solid Substances 0.000 claims description 5
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical group [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 4
- WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical compound OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 claims description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 4
- 108010011485 Aspartame Proteins 0.000 claims description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 2
- 239000008118 PEG 6000 Substances 0.000 claims description 2
- 229920002584 Polyethylene Glycol 6000 Polymers 0.000 claims description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims description 2
- 239000001361 adipic acid Substances 0.000 claims description 2
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- 239000000605 aspartame Substances 0.000 claims description 2
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 claims description 2
- 229960003438 aspartame Drugs 0.000 claims description 2
- 235000010357 aspartame Nutrition 0.000 claims description 2
- 229910000019 calcium carbonate Inorganic materials 0.000 claims description 2
- 239000000470 constituent Substances 0.000 claims description 2
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 claims description 2
- 239000008101 lactose Substances 0.000 claims description 2
- 239000007788 liquid Substances 0.000 claims description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 2
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- 239000004575 stone Substances 0.000 claims description 2
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- 235000002906 tartaric acid Nutrition 0.000 claims description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims 1
- 229910052799 carbon Inorganic materials 0.000 claims 1
- 239000006185 dispersion Substances 0.000 claims 1
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- 235000011087 fumaric acid Nutrition 0.000 claims 1
- 229910052739 hydrogen Inorganic materials 0.000 claims 1
- 239000001257 hydrogen Substances 0.000 claims 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 1
- 239000011734 sodium Substances 0.000 claims 1
- 229910052708 sodium Inorganic materials 0.000 claims 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims 1
- 238000004090 dissolution Methods 0.000 abstract description 3
- 238000012216 screening Methods 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
- 235000019441 ethanol Nutrition 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 241000894006 Bacteria Species 0.000 description 4
- 206010012735 Diarrhoea Diseases 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- LNTHITQWFMADLM-UHFFFAOYSA-N gallic acid Chemical class OC(=O)C1=CC(O)=C(O)C(O)=C1 LNTHITQWFMADLM-UHFFFAOYSA-N 0.000 description 4
- 238000001291 vacuum drying Methods 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- 208000008469 Peptic Ulcer Diseases 0.000 description 2
- 208000025865 Ulcer Diseases 0.000 description 2
- 230000000840 anti-viral effect Effects 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 230000003078 antioxidant effect Effects 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 235000013399 edible fruits Nutrition 0.000 description 2
- 235000004515 gallic acid Nutrition 0.000 description 2
- 229940074391 gallic acid Drugs 0.000 description 2
- 210000004400 mucous membrane Anatomy 0.000 description 2
- 208000011906 peptic ulcer disease Diseases 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 150000008442 polyphenolic compounds Chemical class 0.000 description 2
- 235000013824 polyphenols Nutrition 0.000 description 2
- 231100000397 ulcer Toxicity 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 208000007882 Gastritis Diseases 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 206010030216 Oesophagitis Diseases 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 239000004411 aluminium Substances 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 229910000323 aluminium silicate Inorganic materials 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 238000006471 dimerization reaction Methods 0.000 description 1
- HNPSIPDUKPIQMN-UHFFFAOYSA-N dioxosilane;oxo(oxoalumanyloxy)alumane Chemical compound O=[Si]=O.O=[Al]O[Al]=O HNPSIPDUKPIQMN-UHFFFAOYSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000007938 effervescent tablet Substances 0.000 description 1
- ZEPCRIPMALGRJR-UHFFFAOYSA-N ellagic acid, dihydrate Chemical compound O.O.OC1=C(O)C(OC2=O)=C3C4=C2C=C(O)C(O)=C4OC(=O)C3=C1 ZEPCRIPMALGRJR-UHFFFAOYSA-N 0.000 description 1
- 208000006881 esophagitis Diseases 0.000 description 1
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- 229910052742 iron Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 244000000010 microbial pathogen Species 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 229910021647 smectite Inorganic materials 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 229920001864 tannin Polymers 0.000 description 1
- 235000018553 tannin Nutrition 0.000 description 1
- 239000001648 tannin Substances 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
- A61K31/366—Lactones having six-membered rings, e.g. delta-lactones
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Abstract
本发明提供一种鞣花酸‑蒙脱石泡腾剂及其制备方法,具体的,定量称取鞣花酸和PVP‑K30，先将PVP‑K30溶于有机溶剂中，再缓慢的倒入鞣花酸溶液中，在室温下搅拌后，除去多于有机溶剂，使鞣花酸和PVP‑K30共同析出，干燥后粉碎，筛分，得到鞣花酸固体分散体，干燥储存；然后加入适量的酸源、碱源、润滑剂、填充剂和矫味剂；混匀；最后加入PVP无水乙醇溶液制软材，制粒，干燥，过筛，得鞣花酸‑蒙脱石泡腾颗粒。最后制备的泡腾剂口感好,溶解稳定,药剂量大。
Description
技术领域
本发明涉及药物制剂领域，尤其涉及一种鞣花酸-蒙脱石泡腾剂及其制备方法。
背景技术
鞣花酸（Ellagic acid）是一种天然多酚成分，存在于植物组织中，如多种软果、坚果。它是一种多酚二内酯，是没食子酸的二聚衍生物，又被称为没食子酸和胡颓子酸，具有反式没食子酸单宁的结构，分子式为C14H6O8，分子量为302.19，为白色结晶粉末，可溶于甲醇、乙醇、DMSO等有机溶剂。鞣花酸有多种药理作用，如抗氧化、抗肿瘤、抗炎、抗菌、抗病毒等。微溶于水、醇。
蒙脱石是一种由硅、铝和少量铁、镁、钙组成的具有层纹状结构的天然硅铝酸盐，分子是为Al2O9Si3，分子量为282.21。它可以吸附在消化道的黏膜上，具有很强的覆盖消化道的能力。除了保护黏膜外，还可以吸附各种细菌、病毒和毒素，使病原微生物破裂、脱水以至灭活，可用于治疗食管炎、胃炎和消化性溃疡，对于各种原因引起的腹泻有良好的临床疗效。目前，鞣花酸的研究主要在于其抗氧化、抗病毒、治疗癌症等药理作用方面，以及提取工艺、含量测定等，而对于其制剂的研究较少。
发明内容
本发明提供了一种鞣花酸-蒙脱石泡腾剂及其制备方法，为消化性溃疡和腹泻的治疗提供一种安全、高效的鞣花酸和蒙脱石制剂，更好地服务于临床应用。
一种鞣花酸-蒙脱石泡腾剂，其配方组份为：鞣花酸固体分散体为9-11份；蒙脱石为3.3-16.5份、泡腾剂总量为30~50份；填充剂为17.5-50.7份；润滑剂为3份；矫味剂为3份；所述的份数为质量分数；
其中，所述鞣花酸固体分散体的组成为鞣花酸与PVP-K30，二者比例为1:20-40。
其中，其配方优选为鞣花酸固体分散体为10份；蒙脱石为3.3-10份；泡腾剂总量为35-45分；乳糖为29-45.7份、PEG6000为3份、阿斯巴甜为3份；其中，鞣花酸固体分散体的组成为鞣花酸与PVP-K30，二者比例为1:25-35。
其中，所述的泡腾剂的组成为酸源和碱源，酸源选自苹果酸、柠檬酸、酒石酸、富马酸、己二酸中的一种；碱源为碳酸钠、碳酸氢钠、碳酸钾、碳酸氢钾、碳酸钙中的一种；酸源和碱源的质量比为0.8-1.6。
其中，所述的泡腾剂酸源和碱源组合为苹果酸和碳酸氢钠，或柠檬酸和碳酸氢钠，用量比为0.8-1.2。
上述的鞣花酸-蒙脱石泡腾剂的制备方法，其特征在于，包含以下步骤：
（1）定量称取鞣花酸和PVP-K30，先将PVP-K30溶于有机溶剂中，再缓慢的倒入鞣花酸溶液中，在室温下搅拌后，除去多于有机溶剂，使鞣花酸和PVP-K30共同析出，干燥后粉碎，筛分，得到鞣花酸固体分散体，干燥储存；
（2）称取（1）项制备的鞣花酸固体分散体，加入适量的酸源、碱源、润滑剂、填充剂和矫味剂；混匀；
（3）向（2）所的混合物中加入PVP无水乙醇溶液制软材，制粒，干燥，过筛，得鞣花酸-蒙脱石泡腾颗粒。
其中，步骤（2）所述的众组分按等量递增的方式混合均匀。
鞣花酸具有杀菌的效果，蒙脱石能够吸附各种细菌。蒙脱石治疗腹泻溃疡的效果很好，鞣花酸能防止感染，保护溃疡伤口免受细菌侵袭，并对大肠杆菌等细菌有抑制作用，但目前为止并没有将这两种有效物质结合在一起治疗腹泻的药物。
发明人将鞣花酸首先制成固体分散体，可以提高其溶解度和稳定性。鞣花酸在水中的溶解度为2.30 μg/mL，在甲醇中的溶解度为9.14 μg/mL；鞣花酸固体分散体在水中的溶解度为7.83 μg/mL，在甲醇中的溶解度为1035.88 μg/mL。分析表明，相较于鞣花酸，鞣花酸固体分散体在水中的溶解度可以增大3.6倍，在甲醇中的溶解度可以增大113倍。
最终产品为泡腾剂，解决了鞣花酸固体分散体和蒙脱石制剂口感苦涩，影响服用的问题。
本发明有益效果
（1）通过对鞣花酸的加工，提供了其稳定性和溶解度，相当于增加了单片泡腾片含药剂量，更适用于溶解服用；
（2）本发明采用湿法混合制粒的方法进行制粒，工艺简单、操作方便、成本低；
（3）颗粒剂的制备受环境影响较大，空气的湿度会影响制备效果，本发明用聚乙二醇把碳酸氢钠进行包合，将包封后的碳酸氢钠进一步粉碎，作为泡腾剂的碱源，确保制备过程中对水分的严格控制；
（4）口感好，方便各个年龄段食用，儿童用药顺应性好。
具体实施方式
实施例1：
1) 定量称取鞣花酸40 mg和PVP-K30 1.20 g，将溶解在甲醇中的的PVP-K30溶液缓慢的倒入鞣花酸溶液中，在室温下搅拌30 min后，减压蒸发除去甲醇，使鞣花酸和PVP-K30共同析出固体，真空干燥后，粉碎，过筛，得到鞣花酸PVP-K30固体分散体，干燥储存。
2) 分别称取上述制备的鞣花酸固体分散体1.2 g，及蒙脱石1.2 g、柠檬酸1.8 g、碳酸氢钠1.8 g、润滑剂0.36 g、填充剂5.28 g和矫味剂0.36 g，按等量递增的方式混合均匀。
3) 向上述所得混合物中加入适量的5%PVP无水乙醇溶液制软材，制粒，干燥，过筛，得鞣花酸-蒙脱石泡腾颗粒。
实施例2：
1) 定量称取鞣花酸40 mg和PVP-K30 1.20 g，将溶解在甲醇中的的PVP-K30溶液缓慢的倒入鞣花酸溶液中，在室温下搅拌30 min后，减压蒸发除去甲醇，使鞣花酸和PVP-K30共同析出固体，真空干燥后，粉碎，过筛，得到鞣花酸PVP-K30固体分散体，干燥储存。
2) 分别称取上述制备的鞣花酸固体分散体1.2 g，及蒙脱石1.0 g、苹果酸2.6 g、碳酸氢钠2.2 g、润滑剂0.36 g、填充剂4.28 g和矫味剂0.36 g，按等量递增的方式混合均匀。
3) 向(2)所得混合物中加入适量的5%PVP无水乙醇溶液制软材，制粒，干燥，过筛，得鞣花酸-蒙脱石泡腾颗粒。
实施例3
1) 定量称取鞣花酸40 mg和PVP-K30 1.20 g，将溶解在甲醇中的的PVP-K30溶液缓慢的倒入鞣花酸溶液中，在室温下搅拌30 min后，减压蒸发除去甲醇，使鞣花酸和PVP-K30共同析出固体，真空干燥后，粉碎，过筛，得到鞣花酸PVP-K30固体分散体，干燥储存。
2) 分别称取上述制备的鞣花酸固体分散体1.2 g，及蒙脱石1.2 g、柠檬酸2.4 g、碳酸氢钠2.4 g、润滑剂0.36 g、填充剂4.08 g和矫味剂0.36 g，按等量递增的方式混合均匀。
3) 向上述所得混合物中加入适量的5%PVP无水乙醇溶液制软材，制粒，干燥，过筛，得鞣花酸-蒙脱石泡腾颗粒。
对比例1
1) 定量称取鞣花酸25mg和蒙脱石1.2 g、柠檬酸2.4 g、碳酸氢钠2.4 g、润滑剂0.36g、填充剂4.08 g和矫味剂0.36 g，按等量递增的方式混合均匀。
2) 向上述所得混合物中加入适量的5%PVP无水乙醇溶液制软材，制粒，干燥，过筛，得鞣花酸-蒙脱石泡腾颗粒。
实验结果：泡腾剂放入水中，有少量的不溶性颗粒。继续降低鞣花酸载药量做到泡腾后无不溶性颗粒。而水中，几乎检测不到鞣花酸含量。
对比例2：
1) 定量称取鞣花酸40 mg和PVP-K30 1.20 g，将溶解在甲醇中的的PVP-K30溶液缓慢的倒入鞣花酸溶液中，在室温下搅拌30 min后，减压蒸发除去甲醇，使鞣花酸和PVP-K30共同析出固体，真空干燥后，粉碎，过筛，得到鞣花酸PVP-K30固体分散体，干燥储存。
2) 分别称取上述制备的鞣花酸固体分散体1.2 g，及蒙脱石1.2 g，并加入矫味剂0.36 g，按等量递增的方式混合均匀。
实验结果：虽然通过矫味剂调整了鞣花酸固体分散剂和蒙脱石制剂的口味，但是溶解后服用，不再发苦，仍然发涩，影响服用。
Claims (6)
1.一种鞣花酸-蒙脱石泡腾剂，其特征在于，其配方组份为：鞣花酸固体分散体为9-11份；蒙脱石为3.3-16.5份、泡腾剂总量为30~50份；填充剂为17.5-50.7份；润滑剂为3份；矫味剂为3份；所述的份数为质量分数；
其中，所述鞣花酸固体分散体的组成为鞣花酸与PVP-K30，二者比例为1:20-40。
2.根据权利要求1所述的鞣花酸-蒙脱石泡腾剂，其特征在于，其配方优选为鞣花酸固体分散体为10份；蒙脱石为3.3-10份；泡腾剂总量为35-45分；乳糖为29-45.7份、PEG6000为3份、阿斯巴甜为3份；其中，鞣花酸固体分散体的组成为鞣花酸与PVP-K30，二者比例为1:25-35。
3.根据权利要求1所述的鞣花酸-蒙脱石泡腾剂，其特征在于，所述的泡腾剂的组成为酸源和碱源，酸源选自苹果酸、柠檬酸、酒石酸、富马酸、己二酸中的一种；碱源为碳酸钠、碳酸氢钠、碳酸钾、碳酸氢钾、碳酸钙中的一种；酸源和碱源的质量比为0.8-1.6。
4.根据权利要求3所述的鞣花酸-蒙脱石泡腾剂，其特征在于，所述的泡腾剂酸源和碱源组合为苹果酸和碳酸氢钠，或柠檬酸和碳酸氢钠，用量比为0.8-1.2。
5.一种权利要求1所述的鞣花酸-蒙脱石泡腾剂的制备方法，其特征在于，包含以下步骤：
（1）定量称取鞣花酸和PVP-K30，先将PVP-K30溶于有机溶剂中，再缓慢的倒入鞣花酸溶液中，在室温下搅拌后，除去多于有机溶剂，使鞣花酸和PVP-K30共同析出，干燥后粉碎，筛分，得到鞣花酸固体分散体，干燥储存；
（2）称取（1）项制备的鞣花酸固体分散体，加入适量的酸源、碱源、润滑剂、填充剂和矫味剂；混匀；
（3）向（2）所的混合物中加入PVP无水乙醇溶液制软材，制粒，干燥，过筛，得鞣花酸-蒙脱石泡腾颗粒。
6.根据权利要求5所述的制备方法，其特征在于，步骤（2）所述的众组分按等量递增的方式混合均匀。
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