小儿开胃增食凝胶提取工艺考察及成型工艺优选

Investigation of extraction processes for paediatric appetite-enhancing gels and optimisation of formulation techniques

摘要

目的: 优选小儿开胃增食凝胶的提取工艺及成型工艺。方法: 以连翘苷含量、干膏率及总黄酮含量作为考察指标,采用层次分析法(analytic hierarchy process,AHP)结合CRITIC(criteria importance through intercriteria correlation)法计算各指标的综合权重系数,以加水倍数、提取时间和提取次数为考察因素,以多指标综合评分与Box-Behnken设计-响应面法结合设计实验,考察小儿开胃增食凝胶的最佳水提工艺。以外观性状、黏附力等评价标准优选小儿开胃增食凝胶的成型工艺。结果: 优选出小儿开胃增食凝胶的最佳提取工艺为加10倍量水、提取时间为1.5 h、提取次数为3次,并通过验证实验确定了小儿开胃增食凝胶的提取工艺稳定可行。筛选出小儿开胃增食凝胶的最佳成型工艺为卡拉胶∶青稞β-葡聚糖∶蔗糖∶水(2 g∶1 g∶1 g∶30 mL)。结论: 基于质量源于设计理念,采用多指标综合评分与Box-Behnken响应面法结合优选得到小儿开胃增食凝胶提取工艺,再以外观性状、黏附力等评价标准优选小儿开胃增食凝胶的成型工艺,可为该方剂的现代提取研究及儿童复方制剂的剂型开发提供一定的数据参考。

Abstract

Objective: To optimize the extraction and formulation processes for paediatric appetite-enhancing Gel (PAG). Methods: The content of forsythoside, dry extract yield, and total flavonoid content in PAG were used as evaluation indicators. The analytic hierarchy process (AHP) combined with the criteria importance through intercriteria correlation (CRITIC) method was employed to calculate the comprehensive weighting coefficients for each indicator. The factors considered were water-to-raw-material ratio, extraction time, and extraction number. A multi-indicator comprehensive scoring method combined with the Box-Behnken design-response surface methodology (BBD-RSM) was used to design the experiment, aiming to determine the optimal water extraction process for PAG. The formulation process of PAG was optimized based on evaluation criteria including appearance and adhesiveness. Results: The optimal process for PAG was determined to be a water-to-raw-material ratio of 10-fold, extraction for 1.5 h, and three extraction cycles. Validation experiments confirmed that the extraction process for PAG is stable and feasible. The optimal formulation process for PAG was determined to be: carrageenan∶barley β-glucan∶sucrose∶water (2 g∶1 g∶1 g∶30 mL). Conclusion: Based on the quality-by-design principle, the extraction process for PAG was optimized through a combined approach of multi-criteria evaluation and the Box-Behnken response surface methodology. Subsequently, the formulation process for the gel was refined using evaluation criteria such as appearance and adhesiveness. This study provides reference data for the modern extraction research on this formulation and for the development of pediatric preparations.

关键词

小儿开胃增食凝胶 / 提取工艺优化 / AHP-CRITIC混合加权法 / Box-Behnken设计-响应面法 / 成型工艺优选

Key words

paediatric appetite-enhancing gel / extraction process optimization / AHP-CRITIC hybrid weighting method / Box-Behnken design-response surface methodology / optimal selection of molding process

[1] 司梦冉, 蔡君豪, 王桂茂, 等. 推拿联合董氏开胃散治疗脾胃湿热型小儿厌食[J]. 长春中医药大学学报, 2020, 36(1): 116-119.
[2] 邱雪, 王莎, 林诗蓉. 运脾开胃手法治疗脾失健运型小儿厌食症的临床疗效观察[J]. 中国现代药物应用, 2022, 16(19): 165-167.
[3] ALMURISI S, DOOLAANEAA, AKKAWI M, et al. Formulation development of paracetamol instantjelly for paediatric use[J]. Drug Dev Ind Pharm, 2020, 64(8): 1373-1383.
[4] MAWAZI SM, AL-MAHMOOD SMA, CHATTERJEE B, et al. Carbamazepine gel formulation as a sustained release epilepsy medication for pediatric use[J]. Pharmaceutics, 2019, 11(10): 488.
[5] SATYANARAYANA DA, KULKARNI PK, SHIVAKUMAR HG. Gels and jellies as a dosage form for dysphagia patients: a review[J]. Curr Drug Ther, 2011, 6(2): 79-86.
[6] 耿晓. 中医解析小儿厌食: 根源与调理之道[J]. 健康必读, 2025(12): 150-151.
[7] 马思淼, 李玉霞, 付菲菲, 等. 小儿开胃增食合剂治疗小儿厌食症的研究进展[J]. 中医儿科杂志, 2024, 20(6): 108-111.
[8] 桑杲, 王静洁, 王萌萌, 等. 运脾和胃调肝法治疗小儿脾胃病临证经验[J]. 浙江中医药大学学报, 2020, 44(3): 279-282.
[9] 张振巍, 张娜娜, 余秋香, 等. 基于Box-Behnken响应面法的柴胡桂枝汤中4个活性成分的提取工艺优化[J]. 中国现代中药, 2025, 27(12): 2323-2331.
[10] 任晶, 盖玉东, 牟荣, 等. Box-Behnken响应面法优化槐米配方颗粒的提取工艺[J/OL]. 特产研究, 2024-09-12.https://doi.org/10.16720/j.cnki.tcyj.2024.107.
[11] 袁诗农, 王少男, 段绪红, 等. 基于AHP-CRITIC复合熵权法和响应面法的蛇床子盐炙工艺优选[J]. 时珍国医国药, 2023, 34(2): 345-350.
[12] 谢谭芳, 何结思, 程哲, 等. 滇桂艾纳香配方颗粒喷雾干燥工艺的优化[J]. 中成药, 2022, 44(5): 1575-1579.
[13] 石金敏, 周灿, 余绪明, 等. CRITIC-AHP法结合Box-Behnken响应面法优选三金排石合剂提取工艺[J]. 中南药学, 2022, 20(6): 1333-1337.
[14] 胡维稳, 字桂成, 杨玲欢. 三十九味骨愈贴凝胶基质配方及其制备工艺的探索研究[J]. 中国医药科学, 2024, 14(15): 66-69.
[15] 王报捷, 江南, 曾君颖, 等. 盐酸小檗碱双交联水凝胶的制备及其性能初步评价[J]. 今日药学, 2026, 36(6): 428-433.
[16] 高春梅, 柳明珠, 吕少瑜, 等. 海藻酸钠水凝胶的制备及其在药物释放中的应用[J]. 化学进展, 2013, 25(6): 1012-1022.
[17] 卢泰, 杨静, 郑琴, 等. 儿童口服凝胶剂的研究进展与应用概况[J]. 中国新药杂志, 2023, 32(17): 1740-1748.
[18] 万安平, 周雄, 冯育林, 等. 中药菊花挥发油聚合物胶束温敏凝胶的制备与评价[J]. 中国新药杂志, 2023, 32(11): 1163-1170.
[19] 卢泰. 兼具优良口感与易吞性的黄连口服凝胶的制备、表征与评价研究[D]. 成都: 成都中医药大学, 2024.
[20] 张卫华, 聂其霞, 张保献, 等. 黄连解毒凝胶的制备工艺研究[J]. 中国实验方剂学杂志, 2010, 16(2): 11-13.
[21] 字磊, 李艳娟, 李艳芹, 等. 中药复方配伍机制研究方法/策略进展[J]. 中国药房, 2023, 34(11): 1393-1398.
[22] 王晓杰, 张晓清, 李希, 等. 基于多指标的AHP-EWM复合权重法结合BBD响应面法优选活膝祛风酒提取工艺[J]. 中药材, 2024, 47(11): 2829-2834.
[23] 贺方良, 程显隆, 李明华, 等. 权重赋值法在多指标综合评价中的研究进展及其在中药质量评价中的应用展望[J]. 中国现代中药, 2024, 26(1): 224-232.
[24] 蔡锦云, 钟海艺, 李培源. 姜黄素纳米凝胶的制备及其应用研究进展[J]. 中国现代应用药学, 2023, 40(4): 562-568.

基金资助

国家自然科学基金资助项目(82360944);甘肃省自然科学基金资助项目(25JRRA239);甘肃省2025年药品监管科学研究项目(2025GSMPA056);甘肃省中医药科研课题(GZKZ-2025-34);甘肃省2023年度药品监管科学研究项目(2023GSMPA027)