Sonoran Biosciences, Tempe, Arizona, USA.
Department of Orthopaedic Surgery, University of Arizona College of Medicine, Phoenix, Arizona, USA.
Pain Med. 2023 Feb 1;24(2):113-121. doi: 10.1093/pm/pnac119.
A local anesthetic that provides analgesia lasting at least three days could significantly improve postoperative pain management. This study evaluated the analgesic efficacy and safety of an extended-release formulation of bupivacaine based on the injectable hydrogel carrier poly(N-isopropylacrylamide-co-dimethylbutyrolactone acrylamide-co-Jeffamine M-1000 acrylamide) (PNDJ).
The efficacy of PNDJ containing 4% bupivacaine (SBG004) given by peri-incisional subcutaneous injection (SBG004 SC) or wound filling instillation (SBG004 WF) was evaluated compared to saline, liposomal bupivacaine, bupivacaine collagen sponge, bupivacaine-meloxicam polyorthoester, and bupivacaine HCl in a porcine skin and muscle incision model. Mechanical allodynia was assessed by withdrawal from application of von Frey filaments, and local tolerance was evaluated by histology. Bupivacaine pharmacokinetics for SBG004 SC were measured in rabbits (16.5 mg bupivacaine/kg).
Animals demonstrated less mechanical allodynia at incisions receiving SBG004 SC for up to 96 hours postoperatively. Incisions treated with SBG004 SC tolerated more force without a withdrawal indicative of pain compared to saline for 96 hours, and compared to SBG004 WF and all active controls at 24, 48, and 72 hours except bupivacaine-meloxicam polyorthoester at 72 hours. By 49 days, SBG004 was histologically absent and was replaced with granulation tissue infiltrated with immune cells in some areas. In rabbits, Cmax was 41.6 ± 9.7 ng/mL with t1/2 82.0 ± 35.8 hours (mean ± SD).
Peri-incisional SBG004 SC provided extended release of bupivacaine sufficient to reduce sensation of incisional pain for 96 hours, in vivo bupivacaine delivery for at least 7 days, and a favorable local and systemic toxicity profile.
一种能提供至少三天镇痛效果的局部麻醉剂，可以显著改善术后疼痛管理。本研究评估了基于可注射水凝胶载体聚（N-异丙基丙烯酰胺-co-二甲基丁内酯丙烯酰胺-co-Jeffamine M-1000 丙烯酰胺）（PNDJ）的布比卡因延长释放制剂的镇痛效果和安全性。
通过猪皮和肌肉切开模型，评估了经皮切口皮下注射（SBG004 SC）或伤口填充滴注（SBG004 WF）给予 4%布比卡因的 PNDJ（SBG004）与生理盐水、脂质体布比卡因、布比卡因胶原海绵、布比卡因-美洛昔康聚原酸酯和布比卡因盐酸盐的疗效。通过 von Frey 纤维的应用撤出评估机械性痛觉过敏，通过组织学评估局部耐受性。在兔子中测量了 SBG004 SC 的布比卡因药代动力学（16.5mg 布比卡因/ kg）。
动物在术后 96 小时内接受 SBG004 SC 切口的机械性痛觉过敏较轻。与生理盐水相比，接受 SBG004 SC 治疗的切口在 96 小时内可以耐受更大的力而无需撤出以提示疼痛，与 SBG004 WF 和所有活性对照物相比，24、48 和 72 小时除外布比卡因-美洛昔康聚原酸酯在 72 小时。到 49 天，SBG004 在组织学上消失，在某些区域被肉芽组织取代，其中浸润有免疫细胞。在兔子中，Cmax 为 41.6±9.7ng/mL，t1/2 为 82.0±35.8 小时（均值±标准差）。
经皮切口 SBG004 SC 提供了布比卡因的延长释放，足以减少切口疼痛 96 小时的感觉，体内布比卡因输送至少 7 天，具有良好的局部和全身毒性特征。
