Synthesis of the Twin Drug of Ibuprofen and Paracetamol

doi:10.3724/SP.J.1095.2014.30430

Chinese Journal of Applied Chemistry

• Full Papers • Previous Articles Next Articles

Synthesis of the Twin Drug of Ibuprofen and Paracetamol

JIN Chao¹, FU Hualin^1,2*, ZHANG Wei¹, ZHANG Yanli¹, CAO Hang¹, ZHOU Tao¹, LU Chaocheng¹, LIU Mengjiao¹, ZHOU Jianyu¹

(1.Department of Pharmacy;2.Key Laboratory of Animal Disease and Human Health of Sichuan Province,
College of Veterinary Medicine,Sichuan Agricultural University,Ya′an 625014,China)

Received:2013-08-27 Revised:2013-12-28 Published:2014-07-10 Online:2014-07-10
Contact: FU

Abstract

Abstract: The twin drug(PHI) was synthesized by coupling ibuprofen(IPF) and paracetamol(PCM) using dicyclohexylcarbodiimide（DCC） as dehydrating agent, 4-dimethylaminopyridine(DMAP) as catalyst, and anhydrous acetone and ethyl acetate as reaction solvents. PHI was purified by recrystallization and its structure was confirmed by IR and 1H NMR spectroscopy. The effect of catalyst, dehydrating agent, reaction time, feed ratio and reaction solvents on the yield of the product was investigated. The reaction conditions were optimized by the orthogonal test. The optimized reaction conditions are:the molar ratio of raw materials is n(PCM)∶(IPF)=1∶1.5, the optimal amount of DMAP is 10% mass fraction of ibuprofen; the volume of solvent is 70 mL(the volume ratio of ethyl acetate and acetone is 1∶1) and the reaction time is 8 h. Under the optimized conditions, the yield of target is 66.5%.

Key words: Ibuprofen, paracetamol, twin drug, dicyclohexylcarbodiimide/dimethylaminopyridine

CLC Number:

O625.3

JIN Chao1, FU Hualin1,2*, ZHANG Wei1, ZHANG Yanli1, CAO Hang1, ZHOU Tao1, LU Chaocheng1, LIU Mengjiao1, ZHOU Jianyu1. Synthesis of the Twin Drug of Ibuprofen and Paracetamol[J]. Chinese Journal of Applied Chemistry, DOI: 10.3724/SP.J.1095.2014.30430.

References

[1] LIU Min,ZHANG Wenjun,GAO Ning. Combination Principles and Their Application in the Design of New Drugs[J]. Chem Reag,2009,31(10):795-780(in Chinese).

刘敏,章文军,高宁. 拼合原理及其在新药设计中的应用[J]. 化学试剂,2009,31(10):795-780.

[2] XU Min. Preparation and Application of Benorilate[J]. Chem Eng Equip,2009,4(4):104-105(in Chinese).

徐敏. 贝诺酯的制备及应用[J]. 化学工程与设备,2009,4(4):104-105.

[3] WANG Liuping,YANG Bin. The Pharmacokinetic Study Progress of Acetaminophen[J]. Lishizhen Med Mater Med Res,2011,22(2):469-470(in Chinese).

王柳萍,杨斌. 对乙酰氨基酚药动学研究进展[J]. 时珍国医国药,2011,22(2):469-470.

[4] ZHANG Li,LI Ting,CHEN Li,et al. Overviews of New Preparations of Ibuprofen[J]. Chinese J New Drugs,2006,15(12):952-956(in Chinese).

张莉,李挺,陈莉,等. 布洛芬新制剂及新技术研究进展[J]. 中国新药杂志,2006,15(12):952-956.

[5] Daniels S E,Goulder M A,Aspley S,et al. A Randomised, Five-parallel-group, Placebo-controlled Trial Comparing the Efficacy and Tolerability of Analgesic Combinations Including a Novel Single-tablet Combination of Ibuprofen/paracetamol for Postoperative Dental Pain[J]. Pain,2011,152(3):632-642.

[6] Mehlisch D R,Aspley S,Daniels S E,et al. Comparison of the Analgesic Efficacy of Concurrent Ibuprofen and Paracetamol with Ibuprofen or Paracetamol alone in the Management of Moderate to Severe Acute Postoperative Dental Pain in Adolescents and Adults:a Randomized, Double-blind, Placebo-controlled, Parallel-group, Single-dose, Two-center, Modified Factorial Study[J]. Clin Ther,2010,32(5):882-895.

[7] Paul I M,Sturgis S A,Yang C,et al. Efficacy of Standard Doses of Ibuprofen Alone, Alternating, and Combined with Acetaminophen for the Treatment of Febrile Children[J]. Clin Ther,2010,32(14):2433-2440.

[8] LI Wansheng. Analysis of 33 cases of the Adverse Reactions of Paracetamol[J]. Chinese Rem Clin,2011,11(2):234(in Chinese).

李晚生. 扑热息痛不良反应33例分析[J]. 中国药物与临床,2011,11(2):234.

[9] Larson A M,Polson J,Fontana R J,et al. Acetaminophen-induced Acute Liver Failure: Results of a United States Multicenter, Prospective Study[J]. Hepatology,2005,42(6):1364-1372.

[10] JIA Hongtian,WANG Hongdan. The Research Progress of Pharmacology and Toxicology of Ibuprofen[J]. Heilongjiang Med J,2011,24(1):109(in Chinese).

贾洪田,王宏丹. 布洛芬药理毒理研究进展[J]. 黑龙江医药,2011,24(1):109.

[11] Moore N, Noblet C, Breemeersch C. Focus on the Safety of Ibuprofen at the Analgesic-antipyretic Dose[J]. Therapie,1996,51(4):458.

[12] ZAO Yimei,XIA Dan,AI Caiping,et al. Synthesis and Anti-inflammatory Activities of Ibuprofen Derivatives[J]. Chinese J Med Chem,2005,15(6): 360-362(in Chinese).

赵一玫,夏丹,艾彩萍,等. 布洛芬衍生物的合成及抗炎活性[J]. 中国药物化学杂志,2005,15(6):360-362.

[13] ZHANG Chuntao,LU Maofang,LIU Hengyan. DCC/DMAP Catalyze to Synthesize Phenylpropanol ester of Acetyl Ferulic Acid[J]. China Prac Med,2010,5(23):37-38(in Chinese).

张春桃,卢茂芳,刘恒言. DCC/DMAP催化制备乙酰阿魏酸苯丙醇酯[J]. 中国实用医药,2010,5(23):37-38.

Synthesis of the Twin Drug of Ibuprofen and Paracetamol

PDF

Knowledge

Cited

Abstract

Cite this article

share this article

References

Related Articles 3

Recommended Articles

Metrics

Comments

[1]	Lei YANG, Yunxing ZHANG, Xiaoqin WANG. Preparation and Release Behavior of Ibuprofen Intercalated Hydrotalcite/Starch Gel Composites [J]. Chinese Journal of Applied Chemistry, 2018, 35(7): 781-787.
[2]	LI Ke, ZHANG Jiaoqiang, KANG Shuanyan, SHI Huimin, ZHOU Hongyu, DOU Rongrong. 2-Acryloyloxyethyl Ferrocene Carboxylate:Synthesis and Optimization [J]. Chinese Journal of Applied Chemistry, 2015, 32(7): 765-770.
[3]	LI Yang1, NING Zhigang1, TAN Ying2, SUN Shumiao1, WANG Pixin1*. Preparation and drug-release properties of ibuprofen-loaded and fluorescein-labeled starch-based nanospheres [J]. Chinese Journal of Applied Chemistry, 2011, 28(10): 1114-1121.