药物预防瘢痕形成:烧伤的临床前和临床研究综述。
Pharmaceutical Prophylaxis of Scarring with Emphasis on Burns: A Review of Preclinical and Clinical Studies.
机构信息
The Geneva Foundation, Tacoma, Washington, USA.
Division of Combat Wound Repair, US Army Institute of Surgical Research, Fort Sam Houston, Texas, USA.
出版信息
Adv Wound Care (New Rochelle). 2022 Aug;11(8):428-442. doi: 10.1089/wound.2020.1236. Epub 2021 Feb 24.
The worldwide estimate of burns requiring medical attention each year is 11 million. Each year in the United States, ∼486,000 burn injuries receive medical attention, including 40,000 hospitalizations. Scars resulting from burns can be disfiguring and impair functions. The development of prophylactic drugs for cutaneous scarring could improve the outcomes for burns, traumatic lacerations (>6 million/year treated in U.S. emergency rooms), and surgical incisions (∼250 million/year worldwide). Antiscar pharmaceuticals have been estimated to have a market of $12 billion. Many small molecules, cells, proteins/polypeptides, and nucleic acids have mitigated scarring in animal studies and clinical trials, but none have received Food and Drug Administration (FDA) approval yet. The development of antiscar pharmaceuticals involves the identification of the proper dose, frequency of application, and window of administration postwounding for the indicated wound. Risks of infection and impaired healing must be considered. Scar outcome needs to be evaluated after scars have matured. Once treatments have demonstrated safety and efficacy in rodent and/or rabbit and porcine wound models, human testing can begin, such as on artificially created wounds on healthy subjects and on bilateral-surgical wounds, comparing treatments versus vehicle controls on patient-matched wounds, before testing on separate cohorts of patients. Given the progress made in the past 20 years, FDA-approved drugs for improving scar outcomes may be expected.
全球每年需要医学治疗的烧伤估计有 1100 万例。在美国,每年有大约 48.6 万例烧伤接受医疗护理,其中包括 4 万例住院治疗。烧伤引起的疤痕可能会导致毁容和功能障碍。预防性药物的开发可以改善烧伤、外伤性撕裂伤(美国急诊室每年治疗超过 600 万例)和外科切口(全球每年约 2.5 亿例)的预后。预计抗疤痕药物的市场价值为 120 亿美元。许多小分子、细胞、蛋白质/多肽和核酸在动物研究和临床试验中都能减轻疤痕,但尚未获得美国食品和药物管理局 (FDA) 的批准。抗疤痕药物的开发涉及确定适当的剂量、应用频率和损伤后给药的窗口期。必须考虑感染和愈合受损的风险。在疤痕成熟后,需要对疤痕的结果进行评估。一旦在啮齿动物和/或兔和猪的伤口模型中证明了治疗的安全性和有效性,就可以开始对人体进行测试,例如在健康受试者身上的人工造口和双侧手术伤口上进行测试,在患者匹配的伤口上比较治疗与载体对照,然后在单独的患者队列中进行测试。鉴于过去 20 年取得的进展,预计会有改善疤痕结果的 FDA 批准药物。
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