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HYR-PB21-LA, a potential extended-release bupivacaine formulation, produces long-lasting local anesthesia in rats and guinea pigs
  1. Jiashi Peng1,
  2. Chang Liu2,
  3. Jingjing Liu3,4,
  4. Yihua Wang3,
  5. Xiaorong Lu3,4,
  6. Hongzhang Sun3,
  7. Yunxian Yu5,
  8. Shu Gao3 and
  9. Shanchun Zhang3
  1. 1 Department of Chemistry, Hefei Cosource Pharmaceutical Co., Ltd, Hefei, Anhui, China
  2. 2 Department of Orthopedics, First Affiliated Hospital of Anhui Medical University Department of Medical Oncology, Hefei, Anhui, China
  3. 3 Department of Pharmacodynamics, Hefei Cosource Pharmaceutical Co., Ltd, Hefei, Anhui, China
  4. 4 Anhui Province Key Laboratory of Druggability Evaluation for New Drugs, Hefei, Anhui, China
  5. 5 Department of Epidemiology, School of Public Health, Zhejiang University, Hangzhou, Zhejiang, China
  1. Correspondence to Dr Shanchun Zhang, Department of Pharmacodinamics, Hefei Cosource Pharmaceutical Co., Ltd, 230031 Hefei, China; shanchun.zhang{at}


Background Effective postoperative pain management plays a key role in enhancing recovery of patients after surgery. Bupivacaine hydrochloride is one of the most commonly local anesthetics used for the postoperative pain control. However, the relatively short anesthesia duration of bupivacaine preparations limited their clinical application.

Methods Both guinea pig pin-prick study and rat tail-flick test were performed to evaluate the local anesthesia efficacy of HYR-PB21-LA, a new microparticle suspension injection of bupivacaine pamoate.

Results In the pin-prick test, the complete cutaneous trunci muscle reflex inhibitions were observed at 30 min in all treatment groups containing bupivacaine. In comparison with 6.7 mg/mL HYR-PB21-LA, both 10 and 20 mg/mL HYR-PB21-LA groups had significantly higher area under effect time curve (AUEC) values (p<0.001 and p<0.0001) and slower offset time (p<0.0001). Significantly higher AUEC (p<0.0001) and slower offset time (p<0.0001) were also found in 10 mg/mL HYR-PB21-LA treatment group compared with bupivacaine liposome injectable suspension (liposomal bupivacaine). In the rat tail-flick test, significantly increased local anesthesia effect was lasted for 5 hours after 2.5 mg/mL HYR-PB21-LA administration, which was fivefold longer than bupivacaine hydrochloride. The longer lasted efficacy of significantly increased local anesthesia was also observed in 5 mg/mLHYR-PB21-LA than those in liposomal bupivacaine (8 hour vs 1 hour).

Conclusions The results demonstrated that the HYR-PB21-LA produced longer local anesthesia effect than current clinical preparations of bupivacaine in two animal models. These findings raise the potential clinical value of HYR-PB21-LA as a long-lasting local anesthesia for controlling postsurgical pain in humans.

  • animal studies
  • pharmacology: local anesthetics
  • postoperative pain

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  • JP and CL are joint first authors.

  • Contributors All authors make substantial contributions to this manuscript.

  • Competing interests Competing Interests statement:SZ reports grants from Development and Reform Committee of Anhui Province, grants from Talent Office of Anhui Province, during the conduct of the study; In addition, JP, YW, XL, HS, SG and SZ have a patent PCT patent application number: WO2018177232 pending. All other authors have declared no conflict of interests for this manuscript.

  • Patient consent for publication Not required.

  • Ethics approval The guinea pig pin-prick study and rat tail-flick test were approved by the Animal Care and Use Ethics Committee of Hefei Blooming Drug Safety Evaluation Company.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available on reasonable request. Data relevant to this article are avialable on reasonalbe request.