2. Academic Validation
  3. HR1405-01, a Safe intravenous NSAID with superior anti-inflammatory and analgesic activities in preclinical trials

HR1405-01, a Safe intravenous NSAID with superior anti-inflammatory and analgesic activities in preclinical trials

  • Eur J Med Chem. 2022 May 5;235:114258. doi: 10.1016/j.ejmech.2022.114258.
Hai Ye 1,  Tian Lv 2,  Tao Min 2,  Di Mao 3,  Xingran Chen 2,  Boxiang Ding 2,  Can Zhang 4
Affiliations

Affiliations

  • 1 State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing, 210009, PR China; Nanjing Heron Pharmaceutical Science and Technology Co., Ltd., Nanjing, 211112, PR China; Jiangsu Hot Melt Extrusion Engineering Research Center, Nanjing, 211112, PR China.
  • 2 Nanjing Heron Pharmaceutical Science and Technology Co., Ltd., Nanjing, 211112, PR China.
  • 3 School of Pharmacy, Jiangsu University, Zhenjiang, 212013, PR China.
  • 4 State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing, 210009, PR China; Center of Advanced Pharmaceuticals and Biomaterials, China Pharmaceutical University, Nanjing, 210009, PR China. Electronic address: [email protected].
PMID: 35339101 DOI: 10.1016/j.ejmech.2022.114258
Abstract

Combinational utilization of intravenous non-steroidal anti-inflammatory drugs (NSAIDs) with opium analgesic is an effective alternative modality for pain control after surgery. This regimen is known for reducing the risk of addiction induced by opium analgesic. However, current intravenous NSAIDs have solubility problems, limiting their clinical applications. Although loxoprofen exhibits strong anti-inflammatory and analgesic activities with relatively low ulcerogenicity, its relatively low bioavailability makes it not an ideal drug candidate for intravenous injection. We selected the bioactive metabolite (6) of loxoprofen as a candidate and developed a new intravenous NSAID, HR1405-01. This metabolite exhibited significantly stronger anti-inflammatory and analgesic activities than parecoxib sodium injection or ibuprofen injection. The excellent potency and solubility of HR1405-01 allowed the avoidance of utilization of cosolvent in the formulation, resulting in fewer side effects and a better safety profile. Therefore, HR1405-01 might be a promising candidate for the development of a new intravenous NSAID.

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