CN100345590C - 包含促肝细胞生长素和干扰素的口含片 - Google Patents
包含促肝细胞生长素和干扰素的口含片 Download PDFInfo
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Abstract
一种包含促肝细胞生长素和干扰素的口含片的药物制剂，其每100克含量为：促肝细胞生长素0.02～20%，干扰素104～107IU，填充剂40～99.8%，稳定剂0.05～30%，吸收促进剂0～30%，口味改良剂0～20%，pH值缓冲剂0～25%，该口含片不仅在治疗肝脏疾病方面有良好的协同治疗作用，而且其有效成份的稳定性好，口含吸收使用方便，易于口腔粘膜吸收。
Description
技术领域
本发明属于医药技术领域，涉及一种治疗肝脏疾病尤其是乙型肝炎的包含促肝细胞生长素和干扰素的口腔含化吸收的药物制剂。
背景技术
目前在治疗乙肝方面尚无特效药物，临床上常以保肝和预防病情恶化为治疗重点。
促肝细胞生长素(Hepatocyte Growth Factor，简称HGF)是一种能够刺激肝细胞DNA合成的多肽类物质，又称为肝细胞生长因子、肝细胞生长刺激因子等，通常是从动物肝脏(如乳猪肝脏)提取和基因工程重组方法生产得到的。促肝细胞生长素(HGF)在治疗肝炎、肝损伤和肝纤维化等方面疗效确切，由于HGF口服会被消化酶破坏其生物活性，影响治疗效果，目前临床上使用的HGF均是注射针剂，患者尤其是慢性患者长期使用很不方便。
干扰素是一种临床上广泛使用的具有广谱抗病毒、抗肿瘤及免疫调节功能的生物药品，按其抗原性不同分为α、β和γ三类，并且α-干扰素有20个以上的亚型，如干扰素α-2a、干扰素α-1b和干扰素α-2b等，β-干扰素有4个亚型，γ-干扰素有1个亚型。目前，临床上使用的主要是α-干扰素。
中国发明专利申请号95101216.9和98105384.X分别公开了干扰素与胸腺素和白细胞介素的口含片技术，这两项技术虽然在肝病防治上有较好的作用，但其功效成份均是以提高自身免疫为主，对那些肝细胞受损严重而急需恢复肝功能和保护肝细胞的患者的治疗功效比较单一。
发明内容
本发明的目的是提供一种通过口腔含化吸收的包含促肝细胞生长素和干扰素的药物制剂，它能很好保持HGF和干扰素的活性并通过口腔粘膜吸收来达到治疗肝脏疾病的作用，不仅有保护肝细胞、恢复肝功能、调节免疫和抗病毒的协同作用，而且还有使用方便、易于被患者接受和顺应性好等优点。
本发明采用的解决方案是：将促肝细胞生长素和干扰素制成口含片，使其易于在口腔唾液的作用下溶解而释放出HGF和干扰素通过口腔粘膜吸收。
本发明具体组份设计方案及每100克含量为：
促肝细胞生长素0.02～20％，干扰素104～107IU，填充剂40～99.8％，稳定剂0.05～30％，吸收促进剂0～30％，口味改良剂0～20％，PH值缓冲剂0～25％。
应该说明的是，填充剂是用来稀释和吸收促肝细胞生长素和干扰素、便于黏合压片成型和易于在口腔溶化的药用辅料，选用淀粉、淀粉浆、糊精、阿拉伯胶浆、明胶浆、糖粉、乳糖、聚乙二醇中的一种或多种组合；
稳定剂的作用是用来保护促肝细胞生长素和干扰素在药品保存期内稳定存在和避免降低其活性的药用辅料，选用赖氨酸、精氨酸、谷氨酸、组氨酸、甘氨酸、羟乙基淀粉、羟甲基淀粉、低分子右旋糖酐、甘露醇、山梨醇、木糖醇、氯化钠、葡萄糖和聚乙烯吡咯酮中的一种或多种组合；
吸收促进剂有促进促肝细胞生长素和干扰素在口腔粘膜中的吸收、抑制口腔粘膜内酶、防止促肝细胞生长素和干扰素被口腔粘膜内酶水解的作用，吸收促进剂选用月桂醇硫酸钠、去氧胆酸钠、抑肽酶、丙二醇、氮酮、薄荷醇、杆菌肽、甘氨胆酸钠、水杨酸钠中的一种或多种组合，吸收促进剂在含片配方中可用也可不用，当其含量为0时表示不用该成份；
口味改良剂是改善药物在含化时的口味品质便于患者愉快接受和使用的药用辅料，选用薄荷醇、冰片、甜蜜素、甘草甜素、柠檬酸中的一种或多种组合，口味改良剂在含片配方中可用也可不用，当其含量为0时表示不用该成份；
PH值缓冲剂是调节含片在口腔中溶解后PH值的变化的，选用磷酸盐、枸橼酸盐中的一种或其组合，PH值缓冲剂在含片配方中可用也可不用，当其含量为0时表示不用该成份。
应该指出的是，本发明促肝细胞生长素和干扰素口含片中的吸收促进剂、口味改良剂和PH值缓冲剂可以同时存在或不存在于口含片的药品配方中，也可以是其中一种存在于口含片的药品配方中。
同时应该指出的是，作为本发明口含片制剂中的促肝细胞生长素和干扰素不仅包括通过生物提取或基因工程生产的各种分子量的促肝细胞生长素和干扰素，还包括药物上可以接受的促肝细胞生长素和干扰素的化学修饰体。
另外，本领域技术人员可以理解到，本发明促肝细胞生长素和干扰素口含片的制作方法与常规药物片剂制作方法相似，这里不再赘述。
由于本发明的促肝细胞生长素和干扰素口含片采用上述配方体系，不仅在治疗肝脏疾病方面有良好的协同治疗作用，而且口含吸收使用方便，易于口腔粘膜吸收。
具体实施方式
实施例1.取促肝细胞生长素30克，干扰素(α-2b)2×106IU，赖氨酸80克，乳糖900克，糖粉380克，淀粉浆(17％)1000克，制作方法如下：
先将30克促肝细胞生长素和80克赖氨酸与50克淀粉浆混合均匀制粒、低温干燥后待用。
将2×106IU干扰素α-2b、900克乳糖、380克糖粉、950克的淀粉浆混合均匀，制粒、低温干燥。再将两种颗粒充分混匀，压片即得，使每片重量在0.3克，检测包装即可。
实施例2.在实施例1的成份中加入55克薄荷醇。
先将30克促肝细胞生长素和80克赖氨酸与50克淀粉浆混合均匀制粒、低温干燥后待用。
将55克薄荷醇、2×106IU干扰素、900克乳糖、380克糖粉、950克的淀粉浆混合均匀，制粒、低温干燥.再将两种颗粒充分混匀，压片即制得薄荷口味的肝细胞生长素和干扰素口含片。
实施例3.取促肝细胞生长素70克，干扰素(α-2a)4×106IU，羟乙基淀粉190克，月桂醇硫酸钠95克，淀粉1500克，糊精210克，糖粉220克，0.01M磷酸盐缓冲剂水溶液(PH＝5.5)800毫升。
先将促肝细胞生长素、干扰素、羟乙基淀粉、月桂醇硫酸钠分别溶于800毫升磷酸盐缓冲液中制成混合溶液，混匀待用。再将淀粉、糊精、糖粉混合成均匀粉末，然后将混合溶液喷洒于混合粉末中，搅拌均匀，制粒、低温干燥后压片，使每片重量在0.2克，检测包装即可。
Claims (4)
1.包含促肝细胞生长素和干扰素的口含片，其特征在于每100克口含片药物的各组份及其含量如下：促肝细胞生长素0.02～20％，干扰素104～107IU，填充剂40～99.8％，稳定剂0.05～30％，吸收促进剂0～30％，口味改良剂0～20％，PH值缓冲剂0～25％。
2.根据权利要求1所述的包含促肝细胞生长素和干扰素的口含片，其特征在于：填充剂选用淀粉、淀粉浆、糊精、阿拉伯胶浆、明胶浆、糖粉、乳糖、聚乙二醇中的一种或多种组合；稳定剂选用赖氨酸、精氨酸、谷氨酸、组氨酸、甘氨酸、羟乙基淀粉、羟甲基淀粉、低分子右旋糖酐、甘露醇、山梨醇、木糖醇、氯化钠、葡萄糖和聚乙烯吡咯酮中的一种或多种组合；吸收促进剂选用月桂醇硫酸钠、去氧胆酸钠、抑肽酶、丙二醇、氮酮、薄荷醇、杆菌肽、甘氨胆酸钠、水杨酸钠中的一种或多种组合；口味改良剂选用薄荷醇、冰片、甜蜜素、甘草甜素、柠檬酸中的一种或多种组合；PH值缓冲剂选用磷酸盐、枸橼酸盐中的一种或其组合。
3.根据权利要求1、2所述的包含促肝细胞生长素和干扰素的口含片，所述促肝细胞生长素包括通过生物提取或基因工程生产的各种分子量的促肝细胞生长素。
4.根据权利要求1、2所述的包含促肝细胞生长素和干扰素的口含片，所述干扰素包括通过生物提取或基因工程生产的各种分子量的干扰素，α、β和γ三类干扰素的每个亚型的干扰素。
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1227124A (zh) * | 1998-02-25 | 1999-09-01 | 上海华晨生物技术研究所 | β干扰素含片及其制备方法 |
| CN1367703A (zh) * | 1999-05-31 | 2002-09-04 | 三菱化学株式会社 | Hgf冻干制剂 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1227124A (zh) * | 1998-02-25 | 1999-09-01 | 上海华晨生物技术研究所 | β干扰素含片及其制备方法 |
| CN1367703A (zh) * | 1999-05-31 | 2002-09-04 | 三菱化学株式会社 | Hgf冻干制剂 |
Non-Patent Citations (2)
| Title |
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| 促肝细胞生长素联合α_Lb干扰素治疗慢性活动性肝炎30例疗效观察 邱迎红等，黑龙江医药科学，第22卷第3期 1999 * |
| 干扰素与促肝细胞生长素联合治疗重症肝炎50例 张进化，苏州医学院学报，第19卷第9期 1999 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US20110033556A1 (en) * | 2009-08-07 | 2011-02-10 | Zheming Jin | Natural Pharmaceutical Preparations for Increasing Albumin |
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