CN116440070A - 一种盐酸西替利嗪口服溶液组合物及其制备方法 - Google Patents
一种盐酸西替利嗪口服溶液组合物及其制备方法 Download PDFInfo
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- CN116440070A CN116440070A CN202210010690.3A CN202210010690A CN116440070A CN 116440070 A CN116440070 A CN 116440070A CN 202210010690 A CN202210010690 A CN 202210010690A CN 116440070 A CN116440070 A CN 116440070A
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- cetirizine hydrochloride
- composition
- methylparaben
- sodium
- propylene glycol
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- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims abstract description 93
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Abstract
盐酸西替利嗪是抗组织胺类药物,在临床上主要用于治疗季节性或常年性过敏性鼻炎,由过敏原引起的荨麻疹及皮肤瘙痒。但由于盐酸西替利嗪味苦,因此需加入适当的矫味剂改善口感。目前已上市的盐酸西替利嗪口服溶液,均为多剂量包装,处方中均加入抑菌剂控制需氧菌、酵母菌、霉菌和大肠杆菌生长,但未见其对洋葱伯克霍尔德菌的抑菌效力的研究。本发明提供一种安全、有效、质量可控、口感好的盐酸西替利嗪口服溶液组合物及其制备方法。其组合物包括盐酸西替利嗪原料药、甘油、丙二醇、甜味剂、芳香剂、pH调节剂、抑菌剂、纯化水。
Description
技术领域
本发明属于药物制剂领域,具体涉及一种盐酸西替利嗪口服溶液组合物及其制备方法。
背景技术
盐酸西替利嗪是抗组织胺类药物,为高选择性的H1受体拮抗剂,口服进入体内,迅速与靶细胞膜上的组胺H1受体结合,阻断组胺激活靶细胞。其无明显的抗胆碱和抗5-羟色胺作用,在正常剂量下,不易透过血脑屏障;同时可抑制变态反应初期组胺传递,降低炎性细胞的游走活性和变态反应后期的递质释放,故对迟发期变态反应亦有效。在临床上主要用于治疗季节性或常年性过敏性鼻炎,由过敏原引起的荨麻疹及皮肤瘙痒。
盐酸西替利嗪(式A所示结构)为白色或类白色结晶性粉末,无臭,味苦,具有引湿性。极易溶于水,在甲醇或乙醇中溶解,极难溶解于乙腈或丙酮中。其片剂或胶囊剂崩解时间长,溶出度和溶出速率低,吸收差,生物利用度低;作为水溶性好的药物,可以将其制备成口服溶液,便于儿童、老年人以及吞咽困难的患者服用,但由于盐酸西替利嗪味苦,需加入适量的矫味剂,改善口感,提高儿童服药依从性。
式A盐酸西替利嗪结构式
中国专利CN201110059091.2提供了一种稳定的西替利嗪口服液,在1000mL溶液中包含盐酸西替利嗪1g,丙二醇80~100g,山梨醇360~400g,该口服液配方简单,辅料种类少,稳定性好。但该发明中使用的甜味剂糖精钠带有苦味,甜菊糖带有轻微涩味,导致口服液口感差。
中国专利02130823.3提供了一种含左西替利嗪的抗过敏药物溶液剂。在1000mL药物组合物溶液中包括有左西替利嗪或药学上可接受的盐0.5~20g、聚乙烯吡咯烷酮20~100g、泊洛沙姆5~50g、聚乙二醇400的含量为10~250mL。该发明的缺陷在于处方中含有表面活性剂,对胃肠道具有一定的刺激性,同时处方中使用糖精钠做矫味剂,口感差。
中国专利CN 201310375767.8公开了一种盐酸西替利嗪口服溶液,包括盐酸西替利嗪、甘露醇、羟丙基纤维素、水,本发明的口服溶液有效掩盖了活性成分西替利嗪强烈的苦涩味道,而且显著提高了口服溶液的稳定性,有效降低了西替利嗪的化学降解和毒副作用,降低了活性成分的分子聚集现象,减少了使用风险,提高了用药的安全性。该发明使用的甘露醇甜度仅为蔗糖的70%;25℃时甘露醇在水中的溶解度约为18%,冬季温度低,存储过程中易于析出结晶,且较蔗糖难以复溶;采用的阿司帕坦在人体胃肠道酶作用下可分解为苯丙氨酸、天冬氨酸和甲醇,不适用于苯丙酮酸尿患者,且未见其对洋葱伯克霍尔德菌的抑菌效力的研究。
中国专列CN201410562636.5提供了一种盐酸西替利嗪糖浆,制剂中含有盐酸西替利嗪、谷氨酸钠、黄原胶、蔗糖、pH调节剂、矫味剂和水。其中,盐酸西替利嗪与黄原胶的重量比为1∶1~10,优选为1∶5;谷氨酸钠的用量占糖浆总重量的0.5%~1.0%;pH调节剂为磷酸氢二钠-枸橼酸缓冲液;矫味剂为阿司帕坦、甜菊素或糖精钠。阿斯帕坦滋味口感不错,但是易分解,不稳定;甜蜜素可在肠菌作用下分解为可能有慢性毒性的环己胺,而糖精钠具有潜在致癌作用,两者的安全性受到一定程度的争议,且回味易产生苦味。
中国专利CN202010921323.X发明的盐酸左西替利嗪口服溶液用丙酸作为防腐剂,所述盐酸左西替利嗪口服溶液中丙酸的体积百分数为0.05%~0.15%,以及含有13~18%的丙二醇。该发明中在盐酸左西替利嗪口服溶液中加入丙酸,相比传统防腐剂具有同等的防腐作用,且毒性更小,安全性更高。但该发明中含有较高量的丙二醇,且糖精钠带有苦味,会导致口感变差。
另外,目前已上市的盐酸西替利嗪口服溶液,均为多剂量包装,处方中均加入抑菌剂控制需氧菌、酵母菌、霉菌和大肠杆菌生长,但未见其对洋葱伯克霍尔德菌的抑菌效力的研究。洋葱伯克霍尔德菌近年来已成为临床上较重要的条件致病菌之一,是引起囊性纤维化的重要条件致病菌,属非发酵革兰阴性杆菌,至少由7个基因型组成。广泛存在于土壤和水中,与医院感染密切相关,主要通过水、体温表、喷雾器、静脉导管、导尿管、输液管等在医院内流行播散,在痰标本和重症监护病房分离率高,可致多种医院内感染,包括败血症、心内膜炎、肺炎、伤口感染、脓肿、眼结膜炎等,死亡率高达95%。该菌对β-内酰胺类、氨基糖苷类和多黏菌素等多种抗菌药物耐药,尤其对亚胺培南的耐药率高达90%。目前该菌已列入美国和澳大利亚药典微生物控制项,可见对该菌的重视程度极高。本发明的盐酸西替利嗪口服溶液组合物将通过抑菌效力试验筛选合适的抑菌剂以控制洋葱伯克霍尔德菌。
发明内容
针对上述现有技术的不足,本发明提供一种口感好、安全、有效、质量可控的盐酸西替利嗪口服溶液组合物及其制备方法。该盐酸西替利嗪口服溶液制备工艺简单,稳定性好,口感佳,加入适宜的抑菌剂能有效抑制洋葱伯克霍尔德菌等微生物生长。
为达到本发明的目的,发明人提供的一种盐酸西替利嗪口服溶液组合物包括盐酸西替利嗪原料药、甘油、丙二醇、甜味剂、芳香剂、pH调节剂、抑菌剂、纯化水。
其中,甜味剂包括甘露醇、山梨醇、木糖醇、蔗糖、三氯蔗糖、糖精钠、甜菊素、阿司帕坦中的一种或多种;更优地,甜味剂为山梨醇和三氯蔗糖。三氯蔗糖甜味感非常接近蔗糖,对热、酸、碱十分稳定,安全性高。同时,三氯蔗糖不被龋齿病菌利用,能够减少口腔内病菌,产生的酸量以及链球菌细胞在牙齿表面的粘附,有效的起到抗龋齿作用,特别有益儿童牙齿健康;三氯蔗糖稳定性好,可以长期储存,并且在冷冻干燥过程中不会受到破坏;甜味纯正,与蔗糖甜味相似,不会像其他某些强力甜味剂那样会产生苦后感及异味;价格便宜,相同甜度下比蔗糖便宜,甜度是蔗糖的500~600倍,适合工业化应用。
其中,芳香剂包括草莓香精、香蕉香精、树莓香精、白桃香精、橙味香精、樱桃香精、香草香精中的一种或多种组合;更优地,香精选择白桃香精。
其中,pH调节剂包括柠檬酸、柠檬酸钠、磷酸二氢钠、磷酸氢二钠、醋酸、醋酸钠中的一种或以上;更优地,pH调节剂为醋酸和醋酸钠;pH值4.5~5.5。
进一步地,盐酸西替利嗪口服溶液组合物包括盐酸西替利嗪原料药,甘油,丙二醇,甜味剂:三氯蔗糖与山梨醇,芳香剂:白桃香精,pH调节剂:冰醋酸和醋酸钠,pH值为4.5~5.5;其中三氯蔗糖的含量为0.8~1.2g/L,山梨醇的含量为230~270g/L,白桃香精的含量为4~6g/L。
为抑制盐酸西替利嗪口服溶液中洋葱伯克霍尔德菌、需氧菌、酵母菌、霉菌和大肠杆菌的生长,本发明向口服溶液中加入抑菌剂。
其中,抑菌剂包括丙酸、苯甲酸、苯甲酸钠、羟苯甲酯、羟苯甲酯钠、羟苯乙酯、羟苯乙酯钠、羟苯丙酯、羟苯丙酯钠、羟苯丁酯、羟苯丁酯钠、山梨酸、山梨酸钾中的一种或多种;更优地,抑菌剂为羟苯甲酯和山梨酸钾组合,例如实施例22~24,在对口服制剂的抑菌效力评判实验中,羟苯甲酯和山梨酸钾组合时,细菌与真菌减少lg值均满足抑菌效力评判标准。
其中,当羟苯甲酯和山梨酸钾比例在6:5时,且两者总共用量在1.1g/L~3.3g/L之间时,可以对洋葱伯克霍尔德菌等微生物有较好的抑制生长的作用。
进一步地,盐酸西替利嗪口服溶液组合物包括盐酸西替利嗪原料药,甘油,丙二醇,甜味剂:三氯蔗糖与山梨醇,芳香剂:白桃香精,pH调节剂:冰醋酸和醋酸钠(pH值为4.5~5.5),其中三氯蔗糖的含量为0.8~1.2g/L,山梨醇的含量为230~270g/L,白桃香精的含量为4~6g/L;抑菌剂:羟苯甲酯和山梨酸钾。
同时,配方中添加4%(质量比体积)以上的丙二醇可以显著增强抑菌剂在本品中的除洋葱伯克霍尔德菌外的其他细菌和真菌的抑菌效力,进一步地发现配方中添加6%以上丙二醇能显著增加对洋葱伯克霍尔德菌的抑菌效力,但丙二醇用量达到10%以上会明显影响口感,增加苦涩回味,因此,进一步地确定配方中添加6%~10%的丙二醇,能显著增强对洋葱伯克霍尔德菌的抑菌效力,并且具有维持相对良好的适口性。为保证本发明的质量稳定可控,处方用量如下:
进一步地,盐酸西替利嗪口服溶液组合物的处方为:
盐酸西替利嗪口服溶液组合物的处方还可以为:
盐酸西替利嗪口服溶液组合物的处方为:
进一步地,本发明还提供一种抑菌剂组合物,其活性成分包括羟苯甲酯、山梨酸钾和丙二醇,该抑菌剂可用于抑制洋葱伯克霍尔德菌生长。
进一步地,上述抑菌剂组合物中,羟苯甲酯、山梨酸钾、丙二醇之间的质量比为0.1~1.8:0.5~1.5:60~80。
本发明还提供一种盐酸西替利嗪口服溶液的制备方法,具体包括以下内容:
1、制备:取适量纯化水,加热至50~60℃,称取羟苯甲酯加入并搅拌溶解,冷却至室温;
2、加入处方量的山梨醇、三氯蔗糖、醋酸钠、山梨酸钾搅拌溶解,再加入甘油和丙二醇搅拌分散;
3、将盐酸西替利嗪加入并溶解完毕后,加入白桃香精分散均匀;
4、并用冰醋酸调节pH至4.5~5.5,随后用纯化水定容至1L,分散均匀后即得。
本发明的有益效果是:
(1)本发明盐酸西替利嗪口服溶液组合物,甜味剂采用山梨醇和三氯蔗糖组合,并通过加入白桃香精,极好地掩盖了盐酸西替利嗪的苦味,极大地改善了口服液口感。
(2)本发明发现采用羟苯甲酯和山梨酸钾的抑菌剂组合,控制比例在6:5时,且两者总共用量在1.1g/L~3.3g/L之间时,可以对洋葱伯克霍尔德菌等微生物有较好的抑制生长的作用。同时配方中添加4%以上的丙二醇可以显著增强抑菌剂在本品中的抑菌效力,进一步得发现配方中添加6%~10%的丙二醇,能显著增强对洋葱伯克霍尔德菌的抑菌效力,并且具有良好的适口性。
(3)本发明制剂工艺简单,重复性高,在40℃条件下加速6月稳定性好,开瓶3月研究微生物未见增长,抑菌效果好。
具体实施方式
本发明内容包括但不限于以下实施例,熟悉本领域的技术人员根据上述发明内容对实施方案进行非本质的改进和调整,仍属于本发明的保护范围。
实施例1~16盐酸西替利嗪口服溶液组合物口感筛选样品
表1甜味剂对口感影响的筛选处方
成分 | 实施例1 | 实施例2 | 实施例3 | 实施例4 | 实施例5 | 实施例6 | 实施例7 |
盐酸西替利嗪 | 1g | 1g | 1g | 1g | 1g | 1g | 1g |
甘油 | 200g | 200g | 200g | 200g | 200g | 200g | 200g |
甘露醇 | 300g | / | / | / | / | / | / |
蔗糖 | / | 300g | / | / | / | / | / |
山梨醇 | / | / | 150g | 250g | 300g | 250g | 250g |
糖精钠 | / | / | / | / | / | 0.1g | / |
甜菊素 | / | / | / | / | / | / | 0.1g |
三氯蔗糖 | 1g | 1g | 1g | 1g | 0.5g | / | / |
白桃香精 | 4g | 4g | 4g | 4g | 4g | 4g | 4g |
羟苯甲酯 | 1.2g | 1.2g | 1.2g | 1.2g | 1.2g | 1.2g | 1.2g |
羟苯丙酯 | 0.8g | 0.8g | 0.8g | 0.8g | 0.8g | 0.8g | 0.8g |
醋酸钠 | 4.5g | 4.5g | 4.5g | 4.5g | 4.5g | 4.5g | 4.5g |
冰醋酸 | 0.7g | 0.7g | 0.7g | 0.7g | 0.7g | 0.7g | 0.7g |
纯化水 | 加至1L | 加至1L | 加至1L | 加至1L | 加至1L | 加至1L | 加至1L |
表2芳香剂对口感影响的筛选处方
成分 | 实施例8 | 实施例9 | 实施例10 | 实施例11 | 实施例12 | 实施例13 |
盐酸西替利嗪 | 1g | 1g | 1g | 1g | 1g | 1g |
甘油 | 200g | 200g | 200g | 200g | 200g | 200g |
山梨醇 | 250g | 250g | 250g | 250g | 250g | 250g |
三氯蔗糖 | 1g | 1g | 1g | 1g | 1g | 1g |
草莓香精 | 4g | / | / | / | / | / |
树莓香精 | / | 4g | / | / | / | / |
橙味香精 | / | / | 4g | / | / | / |
香草香精 | / | / | / | 4g | / | / |
白桃香精 | / | / | / | / | 2g | 6g |
羟苯甲酯 | 1.2g | 1.2g | 1.2g | 1.2g | 1.2g | 1.2g |
羟苯丙酯 | 0.8g | 0.8g | 0.8g | 0.8g | 0.8g | 0.8g |
醋酸钠 | 4.5g | 4.5g | 4.5g | 4.5g | 4.5g | 4.5g |
冰醋酸 | 0.7g | 0.7g | 0.7g | 0.7g | 0.7g | 0.7g |
纯化水 | 加至1L | 加至1L | 加至1L | 加至1L | 加至1L | 加至1L |
表3丙二醇对口感影响的筛选处方
成分 | 实施例4 | 实施例14 | 实施例15 | 实施例16 |
盐酸西替利嗪 | 1g | 1g | 1g | 1g |
甘油 | 200g | 200g | 200g | 200g |
丙二醇 | / | 40g | 60g | 100g |
山梨醇 | 250g | 250g | 250g | 250g |
三氯蔗糖 | 1g | 1g | 1g | 1g |
白桃香精 | 4g | 4g | 4g | 4g |
羟苯甲酯 | 1.2g | 1.2g | 1.2g | 1.2g |
羟苯丙酯 | 0.8g | 0.8g | 0.8g | 0.8g |
醋酸钠 | 4.5g | 4.5g | 4.5g | 4.5g |
冰醋酸 | 0.7g | 0.7g | 0.7g | 0.7g |
纯化水 | 加至1L | 加至1L | 加至1L | 加至1L |
实施例1~16制备:取适量纯化水,加热并控温70℃~80℃,加入羟苯甲酯和羟苯丙酯搅拌溶解后,冷却至室温,加入处方量的山梨醇、糖精钠/三氯蔗糖、醋酸钠搅拌溶解,再加入甘油和/或丙二醇搅拌分散后,将盐酸西替利嗪加入并溶解完毕后,加入草莓香精/蓝莓香精/白桃香精分散均匀,并用冰醋酸调节pH至4.5~5.5,随后用纯化水定容至1L,分散均匀后即得。
采用电子舌味觉分析系统SA402B对实施例1~14进行酸、甜、苦、涩及各种回味味觉指标进行检测,结果见表2。
表4口感测试试验结果
注:所有数据均是以人工唾液(参比溶液)为标准的绝对输出值,电子舌测试人工唾液的状态模拟人口腔中只有唾液时的状态;其中Tasteless为无味点,即参比溶液的输出,当实施例的味觉值低于Tasteless时说明无该味道,反之则有。
通过以上口感测试结果可知,甜味剂的筛选处方实施例1~7中,均未检测出酸味,其中实施例1、2、6和7的苦、涩回味相比实施例3、4、5更明显,实施例4中相比实施例3、5甜度更大,同时苦、涩味及其回味更轻微,因此甜味剂选择山梨醇和三氯蔗糖,且明确山梨醇和三氯蔗糖用量需分别达到250mg/ml和1mg/ml,方可有更好的口感。
芳香剂的筛选处方实施例8~13中,实施例9~11检测出酸味,实施例8相比实施例12、13的回味偏苦涩,因此芳香剂选择白桃香精,而在实施例4、12、13的白桃香精用量筛选中,实施例12相比实施例4、12的苦涩回味值更大,因此明确白桃香精用量在4~6mg/ml可有良好口感。
对比实施例4、14、15、16,实施例16中苦味和涩味及其苦涩回味增加明显,说明丙二醇的加入对口感有一定影响,其用量达到10%会使口感明显变差。
实施例17~23盐酸西替利嗪口服溶液组合物抑菌效力筛选样品
表5盐酸西替利嗪口服溶液组合物抑菌效力筛选处方
实施例17~18制备:取适量纯化水,加入相应防腐剂搅拌溶解后,加入处方量的山梨醇、三氯蔗糖、醋酸钠搅拌溶解,再加入甘油和丙二醇搅拌分散后,将盐酸西替利嗪加入并溶解完毕后,加入白桃香精分散均匀,并用冰醋酸调节pH至4.5~5.5,随后用纯化水定容至1L,分散均匀后即得。
实施例19~24制备:取适量纯化水,加热并控温50℃~60℃,加入羟苯甲酯搅拌溶解后,冷却至室温,加入处方量的山梨醇、三氯蔗糖、醋酸钠、丙酸/山梨酸钾搅拌溶解,再加入甘油和丙二醇搅拌分散后,将盐酸西替利嗪加入并溶解完毕后,加入白桃香精分散均匀,并用冰醋酸调节pH至4.5~5.5,随后用纯化水定容至1L,分散均匀后即得。
对于实施例4、实施例14~15和实施例17~24,参考《中国药典》2020年版四部通则1121抑菌效力检查法,除进行大肠埃希菌、金黄色葡萄球菌、铜绿假单胞菌、白色念珠菌和黑曲霉的抑菌效力检测之外,增加对洋葱伯克霍尔德菌群的抑菌效力检查,检查方法如下:
取金黄色葡萄球菌、铜绿假单胞菌、大肠埃希菌、白色念珠菌的琼脂培养物,加入0.9%无菌氯化钠溶液将琼脂表面的培养物洗脱,并将菌悬液转移至无菌试管内,用0.9%无菌氯化钠溶液稀释并制成每1ml含菌数约为108cfu的菌悬液备用。
取洋葱伯克霍尔德菌(ATCC25416)、洋葱伯克霍尔德菌(ATCC BAA-245)、洋葱伯克霍尔德菌(ATCC BAA-247)的琼脂培养物,加入pH7.0无菌氯化钠-蛋白胨缓冲液将琼脂表面的培养物洗脱,并将菌悬液转移至无菌试管内,用pH7.0无菌氯化钠-蛋白胨缓冲液稀释并制成每1ml含菌数约为108cfu的菌悬液备用。
取黑曲霉的新鲜培养物加入适量含0.05%(ml/ml)聚山梨酯80的0.9%无菌氯化钠溶液,将孢子洗脱。然后吸出孢子悬液至无菌试管内,加入适量的含0.05%(ml/ml)聚山梨酯80的0.9%无菌氯化钠溶液制成每1ml含孢子数约为108cfu的孢子悬液备用。
取供试品,分别加入本品装量1%的(107~108cfu/ml)洋葱伯克霍尔德菌(ATCC25416)、洋葱伯克霍尔德菌(ATCC BAA-245)、洋葱伯克霍尔德菌(ATCC BAA-247)、大肠埃希菌、金黄色葡萄球菌、铜绿假单胞菌、白色念珠菌和黑曲霉充分混合,使供试品中的试验菌液均匀分布。置20~25℃避光贮存。分别在第14天和第28天进行存活菌数测定。评判标准见表6,结果见表7。
表6口服制剂的抑菌效力评判标准
注:NI:未增加,是指对前一检测时间,试验菌增加的数量不超过0.5lg。
表7抑菌效力检测结果
根据表7检测结果可知,实施例17和实施例18中分别单独加入山梨酸钾和丙酸作为抑菌剂,对洋葱伯克霍尔德菌等微生物的抑制效果较差,实施例15中的羟苯甲酯和羟苯丙酯组合、实施例19中的羟苯甲酯和丙酸组合对洋葱伯克霍尔德菌的控制效果较单抑菌剂更好,但最优选择为羟苯甲酯和山梨酸钾组合,比例在6:5时,两者总共用量低于0.88g/L时,对洋葱伯克霍尔德菌等微生物的抑制效果不够理想,而达到1.1g/L~3.3g/L之间时,可以对洋葱伯克霍尔德菌等微生物有较好的抑制生长的作用。同时实施例4、14、15的抑菌效力结果对比说明,配方中添加4%以上的丙二醇可以显著增强抑菌剂在本品中除洋葱伯克霍尔德菌外的其他细菌和真菌的抑菌效力,进一步地发现配方中添加6%以上丙二醇能显著增加对洋葱伯克霍尔德菌的抑菌效力,但由表4可知,丙二醇用量达到10%以上会明显影响口感,增加苦涩回味,因此,进一步确定配方中添加6%~10%的丙二醇,能显著增强对洋葱伯克霍尔德菌的抑菌效力,并且维持相对良好的适口性。
实施例25稳定性
本发明按口感和抑菌效力最佳的处方即实施例22制备三批样品,进行加速(40℃±2℃,75%±5%RH)和开瓶稳定性考察,三批产品的有关物质和微生物限度等各项指标均符合要求,具体结果见表8和表9。
表8加速考察结果
表9开瓶考察结果
通过表8加速试验和表9开瓶稳定性试验结果证明,本发明盐酸西替利嗪口服溶液组合物,质量可控,稳定性好,配方中加入的羟苯甲酯和山梨酸钾的抑菌剂组合,在本品储存与使用过程中,能有效控制洋葱伯克霍尔德菌的生长。
Claims (10)
1.一种盐酸西替利嗪口服溶液组合物,包括盐酸西替利嗪原料药,甘油,丙二醇,甜味剂:三氯蔗糖与山梨醇,芳香剂:白桃香精,pH调节剂,纯化水;所述pH调节剂为冰醋酸与醋酸钠,pH值为4.5~5.5;其中三氯蔗糖的含量为0.8~1.2g/L,山梨醇的含量为230~270g/L,白桃香精的含量为4~6g/L。
2.如权利要求1所述的组合物,还包括抑菌剂,其中,抑菌剂为丙酸、苯甲酸、苯甲酸钠、羟苯甲酯、羟苯甲酯钠、羟苯乙酯、羟苯乙酯钠、羟苯丙酯、羟苯丙酯钠、羟苯丁酯、羟苯丁酯钠、山梨酸、山梨酸钾中的一种或多种。
3.如权利要求2所述的组合物,其特征在于,抑菌剂为羟苯甲酯和山梨酸钾混合,羟苯甲酯和山梨酸钾重量比为6:5,两者总共用量在1.1g/L~3.3g/L。
4.如权利要求2所述的组合物,其特征在于,丙二醇的含量为6%~10%。
5.如权利要求2~4任一所述的组合物,其特征在于,组合物的处方为:
6.如权利要求2~5任一所述的组合物,其特征在于,组合物的处方为:
7.如权利要求2~5任一所述的组合物,其特征在于,组合物的处方为:
8.如权利要求2~5任一所述的组合物,其特征在于,组合物的处方为:
9.一种如权利要求2~8任一所述的盐酸西替利嗪口服溶液组合物的制备方法,其特征在于,包括:
(1)取适量纯化水,加热至50~60℃,称取羟苯甲酯加入并搅拌溶解,冷却至室温;
(2)加入处方量的山梨醇、三氯蔗糖、醋酸钠、山梨酸钾搅拌溶解,再加入甘油和丙二醇搅拌分散;
(3)将盐酸西替利嗪加入并溶解完毕后,加入白桃香精分散均匀;
(4)并用冰醋酸调节pH至4.5~5.5,随后用纯化水定容至1L,分散均匀后即得。
10.一种抑菌剂组合物在制备抑制洋葱伯克霍尔德菌生长产品中的应用,其特征在于,所述抑菌剂组合物活性成分包括:羟苯甲酯、山梨酸钾和丙二醇。
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