CN107281480B - 一种猪瘟活疫苗的耐热冻干保护剂 - Google Patents
一种猪瘟活疫苗的耐热冻干保护剂 Download PDFInfo
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Abstract
本发明属于疫苗的技术领域，特别涉及一种猪瘟活疫苗的耐热冻干保护剂；它是由下述重量份数的原料配制而成：1%‑3%肌醇、0.5%‑2%侧金盏花醇、5%‑15%蔗糖、0.5%‑2%阿拉伯胶、0.05%‑0.2%肌氨酸、0.01%‑0.1%维生素C，余量为注射用水；本发明可有效保护猪瘟抗原活力，具有耐热保护作用，可冷藏储存运输，复水性好，不含蛋白、明胶等过敏成分，有效降低疫苗的副反应，原材料来源广泛，制备方法简单，综合成本低廉，易于推广应用。
Description
技术领域
本发明属于疫苗的技术领域，特别涉及一种猪瘟活疫苗的耐热冻干保护剂。
背景技术
猪瘟是危害养猪业的最重要疫病，使用猪瘟活疫苗可有效预防该病的发生。我国研制的猪瘟兔化弱毒苗C株，是世界公认的最理想的猪瘟疫苗。该疫苗多为冻干制品，储存运输条件要求严格，一般需要-15℃保存，在2-8℃仅可保存6个月。较严格的保存条件不仅造成成本提升，能源浪费，在实际生产应用中，也不时有疫苗储存运输不当造成免疫失败而发生猪瘟的例子。因此有必要开发一种冻干耐热保护剂，使其可在2-8℃至少保存18个月，在22℃可保存7天，以更符合生产实践的推广应用。
发明内容
本发明的目的在于克服现有技术中存在的不足而提供的一种猪瘟活疫苗的耐热冻干保护剂。
本发明的目的是这样实现的：一种猪瘟活疫苗的耐热冻干保护剂，其特征在于：它是由下述重量份数的原料配制而成：1%-3%肌醇、0.5%-2%侧金盏花醇、5%-15%蔗糖、0.5%-2%阿拉伯胶、0.05%-0.2%肌氨酸、0.01%-0.1%维生素C，余量为注射用水。
一种猪瘟活疫苗的耐热冻干保护剂，其特征在于：它是由下述重量份数的原料配制而成：1.5%-2.5%肌醇、0.8%-1.5%侧金盏花醇、8%-12%蔗糖、0.8%-1.5%阿拉伯胶、0.1%-0.17%肌氨酸、0.03%-0.08%维生素C，余量为注射用水。
一种猪瘟活疫苗的耐热冻干保护剂，其特征在于：它是由下述重量份数的原料配制而成：2%肌醇、1%侧金盏花醇、10%蔗糖、1%阿拉伯胶、0.15%肌氨酸、0.05%维生素C，余量为注射用水。
本发明中肌醇和侧金盏花醇为多羟基化合物，当冻干过程中脱水后，多羟基化合物的羟基能替代蛋白质表面的水分子的轻基，与蛋白质表面形成一层假定的水化膜，从而保护氢键的连接位点不直接暴露在周围环境中，稳定蛋白质的高级结构，防止蛋白质因冻干而变性，两者合用加强对蛋白抗原的保护，更好的保护猪瘟抗原的活性。
蔗糖是冻干活疫苗中最常见的保护剂，使用最广的一类必要成分，为蛋白质的非特异性稳定剂。蔗糖是其中研究最多、也是公认最有效的保护剂，对阻止蛋白质二级结构的改变、冻干处理过程中及贮藏期内蛋白质多肤链的伸展和聚集起着显著作用，且可以增加疫苗的溶解性，增加抗原离散度。
阿拉伯胶属于大分子聚合物保护剂，其可以优先从蛋白质表面析出、使蛋白质溶液浓度升高从而阻止其他小分子(如糖及多轻基化合物)的结晶、抑制冷冻过程中pH值的剧烈变化等。
肌氨酸在冷冻过程中的主要作用是能升高成品的塌陷温度，阻止因塌陷而引起蛋白质结构的破坏。
维生素C是优良的抗氧化剂，可以提高疫苗整体稳定性，提高贮藏温度，增加贮藏时间，能够抵抗机体氧自由机的破坏，增强机体抵抗力。
猪瘟病毒活性受冻干过程多重因素影响，需选择不同作用机理的冻干保护剂加强保护或协同保护，本发明具有耐热保护作用，可有效保护猪瘟抗原活力，制备的猪瘟活疫苗可在2-8℃保存至少18个月，在22℃保存7天保持病毒含量不变，复水性好，减少了在实际应用中室温操作条件下的抗原损失，不含蛋白、明胶等过敏成分，有效降低疫苗的副反应。原材料来源广泛，制备方法简单，综合成本低廉，易于推广应用。
具体实施方式
实施例1、一种猪瘟活疫苗的耐热冻干保护剂，其特征在于：它是由下述重量份数的原料配制而成：2%肌醇、1%侧金盏花醇、10%蔗糖、1%阿拉伯胶、0.15%肌氨酸、0.05%维生素C，余量为注射用水。
本发明耐热冻干保护剂的制备方法如下：
步骤1）按比例将肌醇、侧金盏花醇、蔗糖、阿拉伯胶溶于注射用水800ml，100℃灭菌30分钟处理，获得溶液1，备用；
步骤2）将肌氨酸、维生素C溶于100ml注射用水，0.22um滤膜过滤，获得溶液2，备用；
步骤3）合并溶液1和溶液2，补足注射用水至1000ml，即为本发明耐热冻干保护剂。
实施例2、耐热冻干保护剂的应用
（1）将上述耐热冻干保护剂与猪瘟病毒悬液1:1混合，定量分装，冷冻干燥后制成猪瘟活疫苗。
（2）同时选择市售某品牌猪瘟活疫苗（兔源），作为对照疫苗。
（3）疫苗检验
将上述市售某品牌猪瘟活疫苗与本发明保护剂疫苗分别放置于2-8℃冷库保存，分别于0月，1月，3月，6月，12月，18月，依据2015版兽药典相关项目进行检验，考察检验结果。为了更接近实际生产，将两种疫苗置于22℃培养箱7天，开展相关检验。检验结果如表1、表2和表3所示：
表1 本发明耐热冻干保护剂疫苗检验结果
表2 市售疫苗检验结果
表3 疫苗22℃保存7天检验结果
检验结果可以看出本发明耐热保护剂疫苗完全符合2015版兽药典相关要求，且可在2-8℃保存至少18个月，在22℃保存7天保持病毒含量不变，优于市售商品。
实施例3、一种猪瘟活疫苗的耐热冻干保护剂，其特征在于：它是由下述重量份数的原料配制而成：1%肌醇、0.5%侧金盏花醇、5%蔗糖、0.5%阿拉伯胶、0.05%肌氨酸、0.01%维生素C，余量为注射用水。
实施例4、一种猪瘟活疫苗的耐热冻干保护剂，其特征在于：它是由下述重量份数的原料配制而成： 3%肌醇、2%侧金盏花醇、15%蔗糖、2%阿拉伯胶、0.2%肌氨酸、0.1%维生素C，余量为注射用水。
实施例5、一种猪瘟活疫苗的耐热冻干保护剂，其特征在于：它是由下述重量份数的原料配制而成：3%肌醇、0.5%侧金盏花醇、5%蔗糖、0.5%阿拉伯胶、0.05%肌氨酸、0.01%维生素C，余量为注射用水。
实施例6、一种猪瘟活疫苗的耐热冻干保护剂，其特征在于：它是由下述重量份数的原料配制而成：1%肌醇、3%侧金盏花醇、5%蔗糖、0.5%阿拉伯胶、0.05%肌氨酸、0.01%维生素C，余量为注射用水。
实施例7、一种猪瘟活疫苗的耐热冻干保护剂，其特征在于：它是由下述重量份数的原料配制而成：1%肌醇、0.5%侧金盏花醇、15%蔗糖、0.5%阿拉伯胶、0.05%肌氨酸、0.01%维生素C，余量为注射用水。
实施例8、一种猪瘟活疫苗的耐热冻干保护剂，其特征在于：它是由下述重量份数的原料配制而成：1%肌醇、0.5%侧金盏花醇、5%蔗糖、2%阿拉伯胶、0.05%肌氨酸、0.01%维生素C，余量为注射用水。
实施例9、一种猪瘟活疫苗的耐热冻干保护剂，其特征在于：它是由下述重量份数的原料配制而成：1%肌醇、0.5%侧金盏花醇、5%蔗糖、0.5%阿拉伯胶、0.2%肌氨酸、0.01%维生素C，余量为注射用水。
实施例10、一种猪瘟活疫苗的耐热冻干保护剂，其特征在于：它是由下述重量份数的原料配制而成：1%肌醇、0.5%侧金盏花醇、5%蔗糖、0.5%阿拉伯胶、0.05%肌氨酸、0.1%维生素C，余量为注射用水。
实施例11、一种猪瘟活疫苗的耐热冻干保护剂，其特征在于：它是由下述重量份数的原料配制而成：3%肌醇、2%侧金盏花醇、5%蔗糖、0.5%阿拉伯胶、0.05%肌氨酸、0.01%维生素C，余量为注射用水。
实施例12、一种猪瘟活疫苗的耐热冻干保护剂，其特征在于：它是由下述重量份数的原料配制而成：1%肌醇、2%侧金盏花醇、15%蔗糖、0.5%阿拉伯胶、0.05%肌氨酸、0.01%维生素C，余量为注射用水。
实施例13、一种猪瘟活疫苗的耐热冻干保护剂，其特征在于：它是由下述重量份数的原料配制而成：1%肌醇、0.5%侧金盏花醇、15%蔗糖、2%阿拉伯胶、0.05%肌氨酸、0.01%维生素C，余量为注射用水。
实施例14、一种猪瘟活疫苗的耐热冻干保护剂，其特征在于：它是由下述重量份数的原料配制而成：1%肌醇、2%侧金盏花醇、15%蔗糖、2%阿拉伯胶、0.2%肌氨酸、0.1%维生素C，余量为注射用水。
实施例15、一种猪瘟活疫苗的耐热冻干保护剂，其特征在于：它是由下述重量份数的原料配制而成： 3%肌醇、0.5%侧金盏花醇、15%蔗糖、2%阿拉伯胶、-0.2%肌氨酸、0.1%维生素C，余量为注射用水。
实施例16、一种猪瘟活疫苗的耐热冻干保护剂，其特征在于：它是由下述重量份数的原料配制而成：3%肌醇、2%侧金盏花醇、5%蔗糖、2%阿拉伯胶、0.2%肌氨酸、0.1%维生素C，余量为注射用水。
实施例17、一种猪瘟活疫苗的耐热冻干保护剂，其特征在于：它是由下述重量份数的原料配制而成：3%肌醇、2%侧金盏花醇、15%蔗糖、0.5%阿拉伯胶、0.2%肌氨酸、0.1%维生素C，余量为注射用水。
实施例18、一种猪瘟活疫苗的耐热冻干保护剂，其特征在于：它是由下述重量份数的原料配制而成：3%肌醇、2%侧金盏花醇、15%蔗糖、2%阿拉伯胶、0.05%肌氨酸、0.1%维生素C，余量为注射用水。
实施例19、一种猪瘟活疫苗的耐热冻干保护剂，其特征在于：它是由下述重量份数的原料配制而成：3%肌醇、2%侧金盏花醇、15%蔗糖、2%阿拉伯胶、0.2%肌氨酸、0.01%维生素C，余量为注射用水。
实施例20、一种猪瘟活疫苗的耐热冻干保护剂，其特征在于：它是由下述重量份数的原料配制而成：1%肌醇、0.5%侧金盏花醇、15%蔗糖、2%阿拉伯胶、0.2%肌氨酸、0.1%维生素C，余量为注射用水。
实施例21、一种猪瘟活疫苗的耐热冻干保护剂，其特征在于：它是由下述重量份数的原料配制而成：3%肌醇、0.5%侧金盏花醇、5%蔗糖、2%阿拉伯胶、0.2%肌氨酸、0.1%维生素C，余量为注射用水。
实施例22、一种猪瘟活疫苗的耐热冻干保护剂，其特征在于：它是由下述重量份数的原料配制而成：3%肌醇、2%侧金盏花醇、5%蔗糖、0.5%阿拉伯胶、0.2%肌氨酸、0.1%维生素C，余量为注射用水。
实施例23、一种猪瘟活疫苗的耐热冻干保护剂，其特征在于：它是由下述重量份数的原料配制而成：3%肌醇、2%侧金盏花醇、15%蔗糖、0.5%阿拉伯胶、0.05%肌氨酸、0.1%维生素C，余量为注射用水。
实施例24、一种猪瘟活疫苗的耐热冻干保护剂，其特征在于：它是由下述重量份数的原料配制而成：3%肌醇、2%侧金盏花醇、15%蔗糖、2%阿拉伯胶、0.05%肌氨酸、0.01%维生素C，余量为注射用水。
Claims (1)
1.一种猪瘟活疫苗的耐热冻干保护剂，其特征在于：它是由下述重量份数的原料配制而成：2%肌醇、1%侧金盏花醇、10%蔗糖、1%阿拉伯胶、0.15%肌氨酸、0.05%维生素C，余量为注射用水。
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