CN1049576C - 硬质多孔松泡体栓及其制造工艺 - Google Patents
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Abstract
硬质多孔松泡体栓，特别是生物制品栓，它有内栓和外膜，其特征在于内栓是药品与基质均匀混合物的硬质多孔松泡体，基质为明胶、海藻胶、聚乙二醇的单一体，外膜为脂溶性物质。其制造工艺的特征为以打泡的方式将药品与基质混合均匀，在泡沫充分的状态下倒模、速冷，冷却后进行低温真空干燥，使栓充分脱水。
这种无水、易为体液溶解的硬质多孔松泡体栓，为含水后稳定性差的药品提供了一种新的剂型，以干扰素栓为例它提供了干扰素供阴道局部给药治疗宫颈炎的稳定剂型。
Description
本发明涉及医用栓及其制法，特别适用于生物制品的栓。
现在市场的栓剂，是个实心体，由药品、基质组成。按基质的不同，现有栓剂分为两类：一类为水溶收(或亲水性)基质栓，另一类为油溶性基质栓，两类栓剂虽然外形可以有许多不同，但栓体都是实心的，药物均匀的分布在基质中，无气泡和孔隙。对于水溶性基质栓而言，其基质是明胶和甘油的混合物，也可以用海藻胶或聚乙二醇和甘油的混合物。为了使栓在人体中迅速(1小时内)溶解，栓的含水量要在50％以上，甘油起着保湿，以防止栓干燥变硬不能被体液迅速溶解的作用。
目前的栓剂一般是通过热熔法或冷压法制成，制备过程中，先将药物与基质混合均匀，热熔法是将混合好药物的基质注入模中，冷却凝固后脱模，包装；冷压法是将混好药物的基质通过模型挤压成一定形状后，包装即成。
干扰素是一种广谱抗病毒、抗肿瘤的生物制品，它对于多种病毒性疾病具有良好的治疗效果，例如：病毒性肝炎、带状疱疹等，最近研究表明妇女宫颈炎的发病与HSV和HPV-16型感染密切相关，应用干扰素治疗宫颈炎——宫颈糜烂已取得了显著疗效。虽然如此，但由于干扰素是一种水溶性生物制品，该制品在液体状态下不稳定、有效期短，临床应用多先制成冻干品后，临用前用水溶解，故多为粉针剂型，而作为外用药局部作用时，也因其稳定性问题而难以规模生产和作为正式药品商品化。用现有的工艺将含水后不稳定的药品(比如生物制品，青霉素等抗生素)制成栓剂，与脂溶性无水基质混合，由于药品量极微，基质与药品的比例悬殊，无法使药品在基质中均匀分布，药效不佳，与水溶性基质混合则：一是水脱不干净，药品很快失活，稳定性差，二是栓为实心体，其含水量可以远远低于现有的50％，但栓体太硬，太致密，体液不能迅速(1小时内)使其溶解，达不到国家规定的标准。
本发明的目的在于提供一种硬质多孔松泡体栓及其制造工艺，使栓能够迅速被体液溶解，而且具有很好的稳定性。
本发明的硬质多孔松泡体栓，特别是生物制品栓，其特征在于内栓是药品与基质均匀混合物的硬质多孔松泡体，基质为明胶、海藻胶，聚乙二醇的单一体，外膜为脂溶性物质。
上述基质也可以是明胶、海藻胶、聚乙二醇的二者或三者外用混配物。
外膜的脂溶性物质可以用半合成混合脂肪酸脂，可可豆油或乌桕脂等，其中可加入适量的防腐剂，抗生素，表面活性剂，着色剂等添加剂，具有润滑和隔离外界的作用，以保证用药方便和内栓在储药过程不因吸水而使药的稳定性下降。
本发明的硬质多孔松泡体栓的制造工艺，特别适用于生物制品的栓，它包括配制基质，加入药液，混合均匀，倒模，冷却，挂膜，包装，其特征在于为以打泡的方式将药液与基质混合均匀，在泡沫充分的状态下倒模、速冷、冷却后进行低温真空干燥，使栓充分脱水。
上述栓的制造工艺，其特征在于在15-60℃打泡5分钟以上，低温干燥时在抽真空状态下从-50℃开始，经30-60小时升温至30℃。
由于本发明的栓是硬质多孔松泡体，体液可以从孔中容易地渗入到栓体内，使无水干燥的含药胶体被迅速溶解，同时由于孔的存在在干燥过程中栓内的水份可以脱净，因而特别适合于生物制品这种不能含有水份的栓，使药的稳定性达到实用程度。
本发明的栓及其制造工艺举例如下。
将100g明胶基质加450g水加热熔融制备后，加入含干扰素的水溶性药液，并计算使每粒栓含干扰素达到所需效价(如10万单位/栓)，在25℃将干扰素、明胶、水的混合体打泡20分钟左右，当全部含水药物基质都成为泡状后，倒入洗净擦干并涂有润滑剂的栓膜中，在泡沫充分的状态下冻结，冻结后将栓取出，送低温真空干燥机干燥，在抽真空状态下干燥温度从-50℃开始经30-60小时升至30℃，制成硬质多孔性内栓，再将内栓外挂上半合成脂肪酸甘油脂，包装。
本发明的栓和制造工艺，除适用于现有水溶性基质栓外，特别适用于现在没有的生物制品的栓，以干扰素栓为例，它提供了干扰素供阴道局部给药治疗宫颈炎的稳定剂型。这种无水、易为体液溶解的硬质多孔松泡体栓，无疑会拓宽生物制品的使用手段和应用范围。
Claims (5)
1、硬质多孔松泡体栓、它有内栓和外膜，其特征在于内栓是药品与基质均匀混合物的硬质多孔松泡体，基质为明胶、海藻胶、聚乙二醇中的一种，外膜为脂溶性物质。
2、如权利要求1所述的栓，其特征在于它是生物制品栓。
3、如权利要求1、2所述的栓，其特征在于基质可以是明胶、海藻胶、聚乙二醇的二种或三种混配物。
4、如权利要求1、2所述硬质多孔松泡体栓的制造工艺，它包括配制基质，加入药液，混合均匀，倒模，冷却，挂膜，包装，其特征在于以打泡的方式将药品与基质混合均匀，在泡沫充分的状态下倒模、速冷，冷却后进行低温真空干燥，使栓充分脱水。
5、如权利要求4所述的制造工艺，其特征在于在15-60℃打泡5分钟以上，低温干燥时在抽真空状态下从-50℃开始，经30-60小时升温至30℃。
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| Application Number | Priority Date | Filing Date | Title |
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| CN94101255A CN1049576C (zh) | 1994-01-27 | 1994-01-27 | 硬质多孔松泡体栓及其制造工艺 |
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| Application Number | Priority Date | Filing Date | Title |
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| CN94101255A CN1049576C (zh) | 1994-01-27 | 1994-01-27 | 硬质多孔松泡体栓及其制造工艺 |
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| Publication Number | Publication Date |
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| CN1105849A CN1105849A (zh) | 1995-08-02 |
| CN1049576C true CN1049576C (zh) | 2000-02-23 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN94101255A Expired - Lifetime CN1049576C (zh) | 1994-01-27 | 1994-01-27 | 硬质多孔松泡体栓及其制造工艺 |
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Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1539499B (zh) * | 2003-04-25 | 2010-06-02 | 天津华立达生物工程有限公司 | 含有干扰素的局部用液态组合物 |
| JP2012520731A (ja) * | 2009-03-20 | 2012-09-10 | インキューブ ラブズ， エルエルシー | 固形薬物送達装置、処方物および使用法 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0172007A2 (en) * | 1984-08-10 | 1986-02-19 | Syntex (U.S.A.) Inc. | Stable liposomes with aqueous-soluble medicaments and methods for their preparation |
| US4675184A (en) * | 1981-11-28 | 1987-06-23 | 501 Sunstar Kabushiki Kaisha | Pharmaceutical composition containing interferon in stable state |
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1994
- 1994-01-27 CN CN94101255A patent/CN1049576C/zh not_active Expired - Lifetime
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4675184A (en) * | 1981-11-28 | 1987-06-23 | 501 Sunstar Kabushiki Kaisha | Pharmaceutical composition containing interferon in stable state |
| EP0172007A2 (en) * | 1984-08-10 | 1986-02-19 | Syntex (U.S.A.) Inc. | Stable liposomes with aqueous-soluble medicaments and methods for their preparation |
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| Publication number | Publication date |
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| CN1105849A (zh) | 1995-08-02 |
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