CN1330378C - 药物组合物 - Google Patents
药物组合物 Download PDFInfo
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- CN1330378C CN1330378C CNB2003101186813A CN200310118681A CN1330378C CN 1330378 C CN1330378 C CN 1330378C CN B2003101186813 A CNB2003101186813 A CN B2003101186813A CN 200310118681 A CN200310118681 A CN 200310118681A CN 1330378 C CN1330378 C CN 1330378C
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Abstract
过去，为了抑制服用感差的药效成分的味道，大量使用药效成分以外的添加剂。因此，作为片剂制剂化的情况下，存在片剂大型化，难以服用的问题。另外药效成分的不适的味道主要通过甜味剂抑制，对于显示胃部不适感症状的人服用量过多并且甜味强的制剂从嗜好性的观点出发不能说是适宜的。另外，对于糖尿病那样的限制糖分摄取的人存在难以使用的问题。通过将服用时产生不适感的药效成分和健胃生药混合，提供改善了服用感的药物组合物。
Description
技术领域
本发明涉及将服用时在口腔内产生苦味，酸味，收敛味等不适感的药效成分制剂时，抑制其不适感效果优异的药物组合物及其制备方法。进一步地，本发明涉及产生上述苦味等不适感的药效成分的掩蔽方法，以及将上述不适感抑制效果优异的生药作为掩蔽剂的使用。
背景技术
作为药品使用的生理活性成分中，服用时在口腔内产生苦味，酸味，收敛味等不适感的成分很多。为了缓和，抑制这种服用时的不适感进行了各种尝试。
过去，为了减轻抗坏血酸钙盐的苦味，提出了混合天冬甜素，水溶性糖类(还原麦芽糖)以及根据需要的游离生理活性成分，压缩成形制剂化的发明。该公报中，公开了长时间抑制抗坏血酸钙盐的苦味的压缩成形制剂，其制备方法，以及掩蔽方法。另外，该公报中记载的发明，抑制糖精的特殊的不适感味也是目的(例如，日本专利文献1)。
但是，该公报中记载的发明，添加物还原麦芽糖的使用量多，片剂大型化而难以服用，制造中存在装置大型化，特殊化等问题。另外，该发明涉及压缩成形制剂的内容，剂型，例如限定为滴剂，糖果等嗜好食品或片剂，含片剂，舍下片等口腔用片剂，不能期望散剂，颗粒剂等剂型的效果。
另外，公开了含有以具有苦味的生理活性成分的金属盐、糖精、还原麦芽糖为主的水溶性糖类的成形性制剂(例如，日本专利文献2)。
但是，与上述压缩成形制剂同样地，添加物还原麦芽糖等水溶性糖类的使用量多，产生片剂大型化且服用困难，制备中装置大型化，特殊化等问题。另外，不能期待散剂，颗粒剂等剂型的效果。
另外，公开了向具有不适味的成分和矫味剂的混合物中施加剪断力得到的粉末体，或者粉末体中添加石蜡成分，进一步将施加剪断力的粉末体制粒而成的掩蔽了不适感味的制粒组合物。而且，作为矫味剂可以列举糖类，合成甜味剂，氨基酸，酸味剂等。该公报记载的发明的目的是提供抑制在口中感觉的不适味，具有良好的矫味并且该效果连续的制粒组合物。另外，以提供便宜的设备、简单的制备方法为目的(例如，日本专利文献3)
但是，制粒组合物的制造方法由简单的工序构成，但为了得到掩蔽的造粒组合物，剪断处理是不可缺少的。因此，由于操作该剪断处理增加工序，在制造成本这一点上存在问题。而且，由于是具有不适味的成分被石蜡成分包围的形态，存在所谓给药后难以从制粒物溶出有效成分的问题。
这样，上述现有技术共同的是大量使用主药成分以外的添加剂，主要使用甜味剂抑制不适感。作为甜味剂可以列举天冬甜素，糖精(磷磺酰苯甲酰亚胺)、还原麦芽糖等。但是，对于胃部显示不适感症状的人服用量多，甜味强的制剂从嗜好性的观点不能说是适宜的。另外，对于糖尿病这类限制糖分摄取的人给药也存在实质上困难的问题。
【日本专利文献1】
日本专利第3110299号公报(第1～4栏)
【日本专利文献2】
日本专利公开2000-103746号公报(第1～3栏)
【日本专利文献3】
日本专利公开2000-191517号公报(第1～3栏)
如上所述，现有技术文献中公开的发明，由于大量使用主药成分以外的添加剂，作为片剂制剂的情况下，存在所谓片剂大型化服用困难的问题。另外，主要地，使用甜味剂抑制有效成分的不适味，作为甜味剂可以列举天冬甜素，糖精，还原麦芽糖等。但是，对于胃部显示不适感类症状的人服用量过多，甜味强的制剂从嗜好性的观点出发不能说是适宜的。另外，对于糖尿病那样限制糖分摄取的人存在给药实质上困难的问题。
因此，在甜味剂等添加剂使用量降低方面，期望可以抑制服用感差的成分的味道的药物组合物，以及其制备方法的开发。另外，作为其制备方法，期望由简单的工序构成的，而且，工序数少、低成本的制备方法。
发明内容
本发明者们，为了解决上述课题，深入研究的结果，令人惊异地发现将服用时产生不适感的生理活性成分与健胃生药混合，服用该组合物时，缓和了该不适感以至完成了本发明。由于在保持健胃生药成分本来的健胃效果的同时，对于生理活性成分作为矫味剂起作用，可以成功地降低过去作为矫味剂使用的甜味剂等添加物的使用量。因此，本发明的药物组合物的制备时，发现不用通常的湿式制粒法，适用干式制粒法。即，通过干式制粒法制造的本发明的药物组合物中，意外地发现，与简单的混合物相比混合的生药的矫味效果增大，而且，提高了药物组合物的服用感。
服用出现消化道副作用的药物，或服用时在口中产生不适感的生理活性成分，通过制成本发明的药物组合物，可以降低或消除上述副作用，另外，可以掩蔽不适的味道。
另外，通过将健胃生药以外的胃肠药成分，服用时在口中产生不适感的生理活性成分，和健胃生药混合，可以掩蔽不适的味道。而且，可以得到胃肠药和健胃生药各自药效的相乘效果。
具体实施方式
本发明，在将服用时产生不适感的生理活性成分制剂化时，可以广泛利用。作为这些成分可以列举如下。制剂化时，可以混合1种和2种以上下述成分。而且，可以将它们与其它药效成分组合而制剂化。
(1)胃肠药成分，服用感差的成分实例
1)作为消化性溃疡治疗药可以列举下列成分。
硫糖铝，醋谷胺铝，吉法酯，舒必利，格龙溴铵，丙谷胺，索法酮，替普瑞酮，苹果酸氯波必利，曲昔派特，普劳诺托，组胺H2受体拮抗剂(雷坭替丁，西咪替丁，法莫替丁，尼扎替丁，罗沙替丁)，质子泵·抑制剂(奥美拉唑)
2)消化器官用药
甲氧氯普胺，乙乳胆胺萘二磺酸盐，马来酸曲美布汀等
3)作为制酸剂
干燥氢氧化铝凝胶，硅酸铝酸镁，硅酸镁，合成硅酸铝，合成铝碳酸镁，氧化镁，氢氧化铝镁，氢氧化铝-碳酸氢钠共沉淀产物，氢氧化铝-碳酸镁混合干燥凝胶，氢氧化铝-碳酸镁共沉淀产物，氢氧化镁，碳酸氢钠，碳酸镁，沉淀碳酸钙，硅酸铝酸镁，无水磷酸氢钙，磷酸氢钙等
(2)具有消化***副作用的生理活性物质服用时在口中产生不适感的成分实例
1)催眠镇静剂：
巴比妥，溴化钠，半琥珀酸丁辛酰胺、左匹克隆等
2)解热镇痛药：
对乙酰氨基酚，甲芬那酸，阿司匹林，乙水杨胺，异丙安替比林，双氯芬酸钠，布洛芬，酮洛芬，吲哚美辛，盐酸替诺立定等
3)镇咳去痰药：
磷酸双氢可待因，右美沙芬氢溴酸盐，柠檬酸异米尼儿，盐酸依普拉酮，盐酸氯哌斯丁，那可丁，愈创木酚，磺酸钾，盐酸麻黄素，d1-盐酸甲基麻黄素等
4)抗组胺药：
马来酸氯苯那敏，盐酸酚妥拉明，富马酸氯马斯丁等
5)强心剂：
氨茶碱，地普罗芬，洋地黄毒甙等
6)镇晕药：
茶苯海明，盐酸地芬尼多，d1-盐酸异丙肾上腺素等
7)糖尿病用药：
盐酸甲福明，盐酸丁二胍等
8)降血压药：
盐酸乙肼苯哒嗪，阿舍西隆，硫酸胍乙啶，盐酸可乐定等
9)无机制剂：
葡萄糖酸钾，氯化钾，硫酸铁，苏氨酸铁，柠檬酸亚铁钠等
10)激素：
***、倍他米松等
11)抗生素：
头孢拉定，头孢克洛，红霉素，克拉霉素，吉他霉素，麦迪霉素，四环素，土霉素，氯霉素，盐酸林可霉素，一硫酸卡那霉素，硫酸巴龙霉素，盐酸万古霉素等
12)驱虫剂，抗病原虫剂：
柠檬酸乙胺嗪，噻苯哒唑，盐酸奎宁，硫酸奎宁，替硝唑等
对于上述生理活性成分，所谓服用时产生不适感，是指苦味，涩味，辛辣味，收敛味，铁味，粉末味，粗糙味感等。
另外，作为上述消化***副作用，例如可以列举显示食欲不振，胃部不适感，胃痛，腹部胀满感，便秘，恶心，呕吐，腹泻等症状。
作为发明药物组合物中使用的健胃生药，可以列举下列生药组。该生药粉末可以在如下所示的生药组中选择组合1个或2个以上。
生药组：桂皮，丁香，生姜，茴香，龙胆，郁金，山椒，陈皮，高良姜，黄柏，紫堇，黄连，当药，厚朴，芍药，砂仁，甘草，黄芩，苦木，苍术，人参，吴茱萸
从这些生药组选择的有效组合如下。给药量，表示适宜本发明的范围。另外，本发明药物组合物中使用的生药的组合，没有任何限定。
给药量
桂皮 50～333mg
丁香 10～50mg
生姜 10～100mg
茴香 10～100mg
龙胆 10～50mg
郁金 10～100mg
山椒 2～30mg
适宜本发明药物组合物的其它生药的种类和给药量如下。对于这些组合，代替上述成分混合，也可以在上述成分中加入。
给药量
陈皮 10～100mg
高良姜 10～100mg
黄柏 10～50mg
紫堇 10～150mg
黄连 10～50mg
当药 10～50mg
厚朴 10～100mg
芍药 10～100mg
砂仁 10～150mg
甘草 10～150mg
黄芩 10～50mg
苦木 10～50mg
苍术 10～50mg
人参 10～150mg
吴茱萸 10～100mg
作为本发明药物组合物中使用的健胃生药的剂型，优选为粉碎的粉末或干燥提取物。另外，更优选为粉碎粉末。生药粉末的粒径优选为500μm以下，更优选为300μm以下，最优选为150μm以下。生药粉末的混合量相对于1重量份服用感差的成分为0.2重量份～2重量份，更优选为0.2重量份～1.0重量份。
在上述生药的粉碎时，可以使用常用方法，例如转动式，流体式，冲击式等粉碎方式。另外，也可以将生药用液氮冷冻后冻干粉碎。
本发明的药物组合物可以进行下列的制剂化。
将1种或2种以上的服用时产生不适感的生理活性成分与健胃生药，以及根据需要的其它的生理活性成分、添加剂等用V型混合机混合，将其用辊式压实机压缩成形，制造成薄片，然后将其用辊式粉碎机振动等来进行整粒。
上述混合时，也可以使用V型混合机以外的，W型混合机，撞击容器混合机，高速搅拌制粒机，万能搅拌混合机等。
湿式制粒时，可以使用转动制粒机，搅拌制粒机，流动层制粒机，喷雾制粒机，离心转动制粒机，转动流动制粒机等湿式制粒机。另一方面，干式制粒法时，可以使用用粉粒状的粘合剂的压实制粒机等干式制粒机等。即使用任何方式制粒也不太损害掩蔽不适味道的效果，但干式制粒法，由于不包括加热工序，保留了生药的风味，可以得到具有更好服用感的药物组合物。所谓干式制粒法是用具有高压的辊压实粉末体，成形，进一步将其整粒得到制粒物的方法。
作为上述湿式制粒法，使用搅拌制粒机或流动层制粒机，将溶解了水等溶剂或粘结剂的溶液添加到粉末体中制粒。另外，可以使用将粉末体溶解或分散到水等溶剂中，将其用喷雾干燥等制粒的喷雾干燥制粒法。由于通过这些制法干燥制粒制品，制品要进行长时间的加热。由于通过这样的加热，降低了本发明所期望的生药的矫味作用，通过这些制法制造的情况下，将生药以外的成分用这些方法制粒，然后将生药在非加热条件下混合是有效的。
如果是用不加热的制法制造的粉粒体，可以将其压缩成形(压片)。片剂的形态可以单层片，另外，也可以是二层，三层片。
本发明的药物组合物，也可以是不适味道的生理活性成分和生药粉末的水分散液制剂的剂型。
本发明的药物组合物，除不适服用感成分和生药外，也可以含有其它生理活性物质。例如，如果是胃肠药可以进一步混合制酸剂，消化剂，整肠剂，粘膜修复剂，止泻剂。
而且，制剂化时，可以混合常用的添加剂。添加剂的种类和数量没有特别限制，但添加剂的量变多，一次给药量不过多是重要的。另外，大量地使用糖类，制剂不变得过甜是必要的。作为添加剂，可以使用例如下列的物质。
结晶纤维素，乳糖，白糖，玉米淀粉，马铃薯淀粉，聚乙烯醇，硬脂酸钙，硬脂酸镁，蔗糖脂肪酸酯，硬脂酸，羧甲醚纤维素，羧甲醚纤维素钙，羧甲醚纤维素钠，大羧甲醚纤维素钠(croscarmellosesodium)，低取代的羟丙基纤维素，羧甲基淀粉钠，含水二氧化硅，轻质硅酸酐，氧化钛，滑石，胃溶性丙烯酸树脂，***胶，羧基乙烯聚合物，羟丙基纤维素，甲基纤维素，乙基纤维素，羟丙基甲基纤维素等。
根据本发明药物组合物的制备方法，可以用便宜的设备简便地制备。另外，根据本发明，由于可以降低甜味剂等添加物的使用量，可以消除现有技术那样的片剂大型化的问题。而且，也可以是散剂和颗粒剂等剂型。
【实施例】
本发明通过下列实施例进一步详细说明，但本发明并不限于这些实施例。
【实施例1～9】
通过下列表1所示的处方，将规定量的干燥粉末状的各成分收集在聚酯袋中，进行单纯混合。在同样的条件下单纯地混合比较处方1～4，作为比较例1～4。
给10名受试者分别服用将这些干燥混合物的一次服用量，通过受试者得到10个阶段的评价。将其点数平均并作为功能评价结果。而且，基于该平均点以下的标准判定。而且，服用时有不适味道的成分为硫糖铝。
判定标准：×：服用感差(功能评价结果：1以上不足3)Δ：普通(功能评价结果：3以上不足6)○：好(功能评价结果：6以上不足8)◎：非常好(功能评价结果：8以上10以下)
【表1】
| 比较处方(mg) 实施例(mg) | |||||||||||||
| 处方No. | ① | ② | ③ | ④ | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 |
| 硫糖铝 | 500 | 500 | 500 | 500 | 500 | 500 | 500 | 500 | 500 | 500 | 500 | 500 | 500 |
| 甘菊蓝磺酸钠 | 2 | 2 | 2 | 2 | 2 | 2 | 2 | 2 | 2 | 2 | 2 | 2 | 2 |
| L-谷氨酸 | 134 | 134 | 134 | 134 | 134 | 134 | 134 | 134 | 134 | 134 | 134 | 134 | 134 |
| 碳酸氢钠 | 150 | 300 | 150 | 300 | 150 | 150 | 150 | 300 | 150 | 150 | 300 | 300 | 150 |
| 合成铝碳酸镁 | 160 | 160 | 160 | 160 | 160 | 160 | 160 | 160 | 160 | 160 | 160 | 160 | 160 |
| α-淀粉酶SS | 20 | 20 | 20 | 20 | 20 | ||||||||
| 脂肪酶AP6 | 20 | 20 | 20 | 20 | 20 | ||||||||
| 桂皮 | 120 | 150 | 100 | 60 | 100 | 100 | 100 | 100 | 100 | ||||
| 砂仁 | 80 | 50 | 30 | ||||||||||
| 丁香 | 30 | 10 | 10 | 10 | 10 | 20 | 40 | ||||||
| 生姜 | 25 | 25 | 20 | 30 | 30 | 30 | 30 | 30 | 40 | ||||
| 茴香 | 25 | 50 | 15 | 12 | 20 | 20 | 10 | 20 | |||||
| 龙胆 | 12 | 10 | 10 | 10 | 10 | ||||||||
| 陈皮 | 50 | 30 | 12 | 30 | 30 | 15 | |||||||
| 山椒 | 15 | 18 | 10 | 15 | 4 | ||||||||
| 郁金 | 30 | 20 | |||||||||||
| 生药合计 | 300 | 305 | 220 | 174 | 180 | 170 | 200 | 200 | 234 | ||||
| 相对于硫糖铝的生药重量比 | 0.6 | 0.61 | 0.44 | 0.35 | 0.36 | 0.34 | 0.4 | 0.4 | 0.47 | ||||
| 甘露醇 | 50 | 80 | 50 | 50 | 50 | 50 | 50 | 50 | 50 | ||||
| L-薄荷醇 | 10 | 5 | 3 | 6 | 2 | 2 | 2 | 2 | 2 | ||||
| 合计(1次服用量) | 946 | 1096 | 986 | 1136 | 1307 | 1337 | 1219 | 326 | 1178 | 1208 | 1388 | 1388 | 1232 |
| 评价点10阶段 | 3× | 2.5× | 2.5× | 2.5× | 6.6○ | 6○ | 6.4○ | 6.4○ | 5.2○ | 6.5○ | 7.5○ | 7.3○ | 8◎ |
从功能试验结果，确认通过混合健胃生药，改善了硫糖铝的服用感。
【试验例】
用下述表2所示的处方，将通过下述各种制粒方法制造的制剂给10名专门的受试者服用，通过受试者得到服用感的评价。
【表2】
(1)挤压制粒
取粘结剂的一部分3g，加水使全部重量为25g，作为粘结剂液体。称量除去L-薄荷醇的上述成分，投入高速搅拌制粒机NMG-1L(株)奈良机械制作所制)中，混合1分钟。然后投入上述粘结剂溶液，在高速搅拌制粒机中混合1分钟。对于该混合物，通过安装了0.6mm筛子的制粒机Dome Gran DGL-1(Fuji Paudal(株)制)进行挤压制粒。而且，将制粒物用Marmerizer 0-230(Fuji Paudal(株)制)进行约30秒钟的圆化处理，将其在60℃用SAFTY OVEN SPH-101(ESPEC(株)制)干燥3小时。根据制造物的收率，算出薄荷醇的量，称量，将其用乳钵粉碎，添加到制造的颗粒。
(2)流动层造粒
取2g粘结剂，向其中加入水成为50g，溶解称为粘结液。进一步地，称量除去薄荷醇的上述成分，过筛，在聚合物袋中混合。将混合物装入流动层制粒机New Marmeizer NQ-125型(Fuji Paudal(株)制)内，将上述粘结剂溶液用顶喷(top-spray)流动层制粒(给气60℃，品温35℃)，然后，通过流动层在60℃干燥30分钟。将制粒物用30目筛子整粒，将通过30目的产品与(1)同样地薄荷醇乳钵粉碎产品混合。
(3)喷雾干燥1
称量除去薄荷醇的上述成分，调整为固体成分为30wt％的水分散液。对于该分散液用喷雾干燥机-L-8型(大川原工机(株)制)，在入口温度约120℃下喷雾干燥。在该制粒物中与(1)，(2)同样的混合薄荷醇粉碎物。
(4)喷雾干燥2
称量除去薄荷醇和健胃生药的上述成分，调整为固形成分为30wt％的水分散液。对于该分散液用喷雾干燥机-L-8型(大川原工机(株)制)，在入口温度约120℃下喷雾干燥。将薄荷醇粉碎粉末与生药粉末与制粒物一起在聚合物袋中混合。
(5)干式制粒
将上述成分称量，过筛，放入辊式压实机-WP90×30(TURBO KOGYO(株)制)并压缩，薄片化。然后，将该薄片用辊式粉碎机-GRN-T53S(日本グラニユレ-タ-(株)制)与30目的振动整粒。
(6)单纯混合
将上述成分称量，在聚合物袋中混合。
将通过上述(1)～(6)的制法制造的制剂分别给10名专门的受试者服用，其服用感用下列标准评价。
标准：×难喝，△稍稍有点难喝，○勉强好喝，◎好喝
结果示于下列表3。
【表3】
结果
| 制法 | 评价 |
| 单纯混合喷雾干燥1喷雾干燥2干式制粒挤压制粒流动层制粒 | ○△○◎△△ |
优选使用生药不经过长时间加热的制粒工序，特别是优选干式制粒法。
通过将服用时产生不适感的生理活性成分与健胃生药混合，在保持健胃生药成分本来的健胃效果的同时，对于生理活性成分作为矫味剂其作用，成功地减少现有的目的下使用的甜味剂等添加物的使用量。而且，由于可以通过干式制粒法制造，作为矫味剂的效果进一步增加，提高了服用感。
通过使用发现消化***副作用的药物、或服用时在口中产生不适感的生理活性成分制成本发明的药物组合物，可以降低或消除上述副作用，另外，可以掩蔽不适感。另外，使用健胃生药以外的胃肠药、服用时口中产生不适感的生理活性成分时，通过混合健胃生药可以掩蔽不适的味道。而且，可以期待胃肠药和健胃生药各自药效的相乘效果。
而且，本发明的药物组合物，由于糖尿病那样的限制糖分摄取的人，容易服用它们，具有以治疗方法的选择广泛，服药伸缩率提高为主的巨大效果。
而且，根据本发明的药物组合物的制造方法，可以通过便宜的设备简便地制造。另外，消除了所谓片剂的大型化问题，使片剂以外的散剂或颗粒剂等各种剂型的供给成为可能。
Claims (4)
1、改善了服用感的药物组合物，其中含有硫糖铝和选自桂皮、砂仁、丁香、生姜、茴香、龙胆、陈皮、山椒和郁金的至少一种生药，通过粉碎的粉末的混合或干式造粒法制造。
2、权利要求1记载的药物组合物，其中上述生药以粒径为500μm以下的粉碎粉末使用。
3、权利要求1或2记载的药物组合物，其中上述生药的混合量，相对于1重量份硫糖铝，为0.2～2重量份。
4、权利要求1～3任意一项记载的药物组合物，其特征在于使用干式制粒法。
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| CN101507770B (zh) * | 2008-07-18 | 2011-01-05 | 天津生机集团股份有限公司 | 治疗马痉挛疝的中药组合物 |
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| KR102428859B1 (ko) * | 2020-05-29 | 2022-08-04 | 동성제약주식회사 | 안전성이 확보된 소화기계 질환 예방 또는 치료를 위한 경구투여용 약학 조성물 |
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| CN117298086B (zh) * | 2023-11-29 | 2024-03-08 | 中国中医科学院中药研究所 | 索法酮在制备预防和/或治疗nlrp3炎性小体介导的疾病的药物中的应用 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1114885A (zh) * | 1994-05-17 | 1996-01-17 | 内蒙古自治区高等院校科技开发集团赤峰公司 | 健身、补肾清脑外用药粉剂 |
| JP2000103746A (ja) * | 1994-10-27 | 2000-04-11 | Takeda Chem Ind Ltd | 成形物およびその製造方法 |
| CN1254520A (zh) * | 1999-11-01 | 2000-05-31 | 济南联合大学 | 复合油树脂调味品 |
| JP2000191517A (ja) * | 1998-12-24 | 2000-07-11 | Lion Corp | 不快な味がマスキングされた造粒組成物及びその製造方法 |
| CN1287488A (zh) * | 1998-04-01 | 2001-03-14 | 中外制药株式会社 | 酒精性胃炎预防剂 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1114885A (zh) * | 1994-05-17 | 1996-01-17 | 内蒙古自治区高等院校科技开发集团赤峰公司 | 健身、补肾清脑外用药粉剂 |
| JP2000103746A (ja) * | 1994-10-27 | 2000-04-11 | Takeda Chem Ind Ltd | 成形物およびその製造方法 |
| CN1287488A (zh) * | 1998-04-01 | 2001-03-14 | 中外制药株式会社 | 酒精性胃炎预防剂 |
| JP2000191517A (ja) * | 1998-12-24 | 2000-07-11 | Lion Corp | 不快な味がマスキングされた造粒組成物及びその製造方法 |
| CN1254520A (zh) * | 1999-11-01 | 2000-05-31 | 济南联合大学 | 复合油树脂调味品 |
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