Lidocaine

点击“蓝字”关注我们 年终盘点微专辑 扫描二维码 可查看更多内容 黄鑫茹博士  刘芳教授 上海交通大学医学院附属第一人民医院 糖尿病神经病变（DPN）一直以来都是临床治疗难点，目前采取的干预措施主要包括针对发病机制和对症止痛两方面。本刊特邀上海交通大学医学院附属第一人民医院刘芳教授盘点当前DPN临床治疗进展，以期为广大临床医生了解领域最新动向提供参考。 一 无痛性DPN 此类患者主要症状为四肢麻木、手套袜套样感觉迟钝，甚至感觉丧失，由于可能无法感知轻微的伤害或温度变化，故发生足病的风险增加。 治疗方面，目前除了对血糖、血脂和血压等进行代谢控制外，一项小样本临床研究显示生活方式干预（低热量饮食减重、足踝锻炼性运动）也能够延缓糖尿病下肢神经病变的进展[1]；临床上主要还是依靠药物进行针对发病机制的对因治疗。 当前临床中广泛应用的针对DPN发病机制治疗的药物包括神经修复药物甲钴胺、强抗氧化剂α-硫辛酸、醛糖还原酶抑制剂依帕司他、改善微循环的前列腺素制剂等血管扩张剂，以及改善神经细胞能量代谢的乙酰左卡尼汀等。 除了活性维生素B12（甲钴胺）外，其他B族维生素衍生物也有作用。一项Ⅲ期随机对照试验（RCT）观察了维生素B1衍生物苯磷硫胺（300 mg/次，2次/d）连续口服1年对DPN患者的治疗作用，结果表明苯磷硫胺可以改善DPN患者的神经症状评分[2]。 胰高糖素样肽-1（GLP-1）具有营养神经的作用[3]，且GLP-1受体在背根神经节神经元中也有表达。一项新研究纳入22例2型糖尿病（T2DM）患者，使用GLP-1受体激动剂（GLP-1RA）利拉鲁肽或司美格鲁肽治疗并随访3个月[4]。结果表明，81.8%的患者在治疗前外周神经束体积已出现病理性增大，随访结束后93%的患者神经束体积有所减小，同时神经病变的严重程度降低，感觉神经传导波幅改善。二肽基肽酶-4抑制剂（DPP-4i）通过抑制DPP-4酶活性，延长GLP-1半衰期而发挥降糖作用。有研究发现，DPP-4i可促进外周神经系统的神经轴突伸长，发挥营养神经的作用[5]。因此，GLP-1RA和DPP-4i均为有前景的DPN治疗药物，值得进一步研究证实。 同样地，另一类降糖药物钠-葡萄糖共转运蛋白2抑制剂（SGLT2i）在治疗DPN方面也显示出一定潜力。研究表明，SGLT2i如恩格列净治疗3个月后可显著改善DPN患者的神经电生理参数，包括改善腓总神经和胫后神经的反射延迟时间、波幅和传导速度[6]。需要指出的是，SGLT2i的主要作用仍是控制血糖，因此DPN患者在使用这类药物时，还应配合血糖监测、生活方式干预等标准治疗方法。 其他新型疗法如C肽皮下注射、肌醇磷酸寡糖、神经生长因子、维生素D等也逐渐被发现和研究。值得一提的是，维生素D缺乏与T2DM人群DPN患病和足溃疡发病显著相关。RCT研究表明，大剂量（800 IU/d，40 000 IU/周）而非小剂量（400 IU/d）补充维生素D，可改善糖尿病神经症状评分（NSS），延缓神经损害进展[7]。 二 痛性DPN 痛性DPN，又称糖尿病痛性周围神经病变（DPNP），患者主要表现为刺痛、烧灼痛、刀割痛、电击样痛、虫咬痛等各种形式的神经病理性疼痛，严重者可影响日常活动，导致失眠、焦虑和抑郁等社会心理障碍，明显降低患者的生活质量。目前，针对糖尿病痛性神经病变主要是对症止痛治疗，包括药物和非药物治疗两方面。 0 1 止痛药物疗法 对症治疗的一线药物包括钙离子通道调节剂普瑞巴林、5-羟色胺-去甲肾上腺素再摄取抑制剂（SNRI）度洛西汀、三环类抗抑郁药（TCA）阿米替林；二线药物如阿片类镇痛药物，由于具有成瘾性，应尽可能避免使用。局部应用药物贴膏也有一定的临床证据，主要包括辣椒素膏/贴剂和利多卡因贴剂，局部外用的8%辣椒素贴片已于2020年7月获得美国食品药品监督管理局（FDA）正式批准，用于成人PDPN患者的治疗。 第三代钙离子通道调节剂美洛加巴林、克利加巴林备受关注。于亚洲进行的两项多中心、双盲、安慰剂对照的Ⅲ期临床研究表明，美洛加巴林10 mg bid组和15 mg bid组患者的每日疼痛评分较基线显著改善[8,9]。2024年，一项由北京大学郭晓蕙教授牵头的多中心、双盲、安慰剂和普瑞巴林对照RCT发现，自治疗第1周起，苯磺酸克利加巴林（HSK16149胶囊）40/80 mg/d显著改善患者疼痛，给药无需滴定，快速起效，且第1~13周均能显著缓解疼痛，而普瑞巴林在第6~13周发挥疗效；此外，克利加巴林治疗的安全性良好，长期用药依从性高，不良反应以轻至中度头晕和嗜睡最为常见[10]。同年5月，克利加巴林成为中国大陆首个获批痛性DPN适应证的药物。 此外，新型药物如肝细胞生长因子（HGF）、血管紧张素Ⅱ受体2拮抗剂以及新型的强效Nav1.7阻滞剂等正在研究或已进入临床试验阶段。一项用质粒制备的HGF治疗DPNP的3期临床研究结果显示，在0、14、90、104天时注射4次HGF制剂VM202，在前9个月的间断治疗期间，HGF并未显著改善神经疼痛，而在不用药的9~12个月延长观察期内，该药明显缓解疼痛，且作用持续到最后一次用药的8个月后，尤其在未服用过加巴喷丁和普瑞巴林的患者中疗效明显，且无明显副作用发生[11]。当然，HGF的安全性和长期缓解疼痛的效果仍需进行更多临床研究加以证实。 0 2 非药物疗法 非药物治疗如电刺激治疗、针灸疗法、神经阻滞/阻断、认知行为疗法、运动和理疗已被系统地研究。一项长达8~10年的随访研究表明，脊髓电刺激是减轻痛性DPN患者疼痛强度的有效方法[12]。小型单盲RCT发现，神经内电刺激治疗可改善痛性DPN患者的总体疼痛感觉、复合静态平衡评分和保护性感觉[13]。然而，包含23项RCT的综述指出，经皮神经电刺激和调频电磁神经刺激无明显止痛效果[14]。迄今关于针灸和认知行为疗法改善DPNP的证据仍不足。 结 语 DPN病理生理机制尚未完全阐明，仍缺乏有效改善疾病的疗法，目前治疗主要包括良好的代谢管理，并进行生活方式干预，以期延缓疾病进展。对于病情明显或加重的DPN患者，则应尽早积极单用或联合应用针对发病机制的药物，并进行相应的足部护理和定期检查。针对当前存在的巨大未被满足的DPN治疗需求，亟待开展相关研究来攻克这一临床难题。 参考文献 （上下滑动可查看） 1. Ghavami H, et al. Agri. 2018; 30(4): 165-170.  2. Bönhof GJ, et al. BMJ Open. 2022; 12(2): e057142. 3. Miyashita A, et al. Int J Mol Sci. 2023; 24(6): 5977. 4. Dhanapalaratnam R, et al. Diabetologia. 2024; 67(3): 561-566. 5. Goldney J, et al. Diabetologia. 2023; 66(10): 1832-1845. 6. El-Haggar SM, et al. Med Clin (Barc). 2024; 163(2): 53-61. 7. Putz Z, et al. Clin Ther. 2022; 44(5): 813-823. 8. Baba M, et al. J Diabetes Investig. 2019; 10(5): 1299-1306. 9. Kato J, et al. Pain. 2019; 160(5): 1175-1185. 10. Guo X, et al. JAMA Netw Open. 2024; 7(8): e2425614. 11. Kessler JA, et al. Clin Transl Sci. 2021; 14(3): 1176-1184. 12. Zuidema X, et al. Neuromodulation. 2023; 26(5): 1074-1080.  13. Sahba K, et al. J Int Med Res. 2022; 50(8): 3000605221109390. 14. Amato Nesbit S, et al. Curr Med Res Opin. 2019; 35(1):15-25.  声明：本文仅供医疗卫生专业人士了解最新医药资讯参考使用，不代表本平台观点。该等信息不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议，如果该信息被用于资讯以外的目的，本站及作者不承担相关责任。 最新《国际糖尿病》读者专属微信交流群建好了，快快加入吧！扫描左边《国际糖尿病》小助手二维码（微信号：guojitnb），回复“国际糖尿病读者”，ta会尽快拉您入群滴！ （来源：《国际糖尿病》编辑部） 版权声明 版权属《国际糖尿病》所有。欢迎个人转发分享。其他任何媒体、网站未经授权，禁止转载。

More patients treated with ZTlido® saw either a decrease or discontinuation of opioid use compared with those treated with the 5% patch (51.9% vs. 45.5%).Of all study patients reporting a decrease in opioid use, significantly more in the ZTlido® group experienced a 20% or greater reduction in opioid use, compared with those treated with 5% lidocaine patch (21.3% vs. 13.4%; P=0.0008).Patients on ZTlido® had a non-significant change in their baseline opioid use (+3.1%; P=0.146), while those using the 5% patch experienced a significant increase in opioid use from baseline (+42.9%; P<0.001). PALO ALTO, Calif., Jan. 13, 2025 (GLOBE NEWSWIRE) -- Scilex Holding Company (Nasdaq: SCLX, “Scilex” or “Company”), an innovative revenue-generating company focused on acquiring, developing and commercializing non-opioid pain management products for the treatment of acute and chronic pain and, following the formation of its proposed joint venture with IPMC Company, in neurodegenerative and cardiometabolic disease, today announced that Pain Medicine News published retrospective claims data on ZTlido® vs. lidocaine 5% patch. Pain Medicine News, the premier trade publication in the pain management space, published decreased opioid utilization demonstrated with ZTlido® (lidocaine topical system 1.8%) in the magazine’s December edition. The article concluded that retrospective claims data showed that Scilex Pharmaceuticals’ flagship product, the branded ZTlido® lidocaine patch, was associated with less use of opioid analgesics in patients with neuropathic pain compared with the 5% lidocaine patch (generic). The researchers looked at claims with a diagnosis of neuropathic pain (postherpetic neuralgia, diabetic peripheral neuropathy or low back pain) in the Optum Claims database from May 1, 2018, to Sept. 30, 2023. Among the key conclusions were that: More patients treated with ZTlido® saw either a decrease or discontinuation of opioid use compared with those treated with the 5% patch (51.9% vs. 45.5%).Of all study patients reporting a decrease in opioid use, significantly more in the ZTlido® group experienced a 20% or greater reduction in opioid use, compared with those treated with 5% lidocaine patch (21.3% vs. 13.4%; P=0.0008).Patients on ZTlido® had a non-significant change in their baseline opioid use (+3.1%; P=0.146), while those using the 5% patch experienced a significant increase in opioid use from baseline (+42.9%; P<0.001). This study further affirms the difference between ZTlido®, as a second-generation lidocaine topical system, versus older, conventional lidocaine patches, and highlights the downstream impact conferred by advanced technology and improved adhesion. The full article may be accessed in the print edition of Pain Medicine News or online in the digital edition at this link: December issue of Pain Medicine News For more information on Scilex Holding Company, refer to www.scilexholding.com For more information on Semnur Pharmaceuticals, Inc., refer to www.semnurpharma.com For more information on Scilex Holding Company Sustainability Report, refer to www.scilexholding.com/investors/sustainability For more information on ZTlido® including Full Prescribing Information, refer to www.ztlido.com. For more information on ELYXYB®, including Full Prescribing Information, refer to www.elyxyb.com. For more information on Gloperba®, including Full Prescribing Information, refer to www.gloperba.com. https://www.facebook.com/scilex.pharm https://www.linkedin.com/company/scilex-holding-company/ info@scilexholding.com About Scilex Holding Company Scilex Holding Company is an innovative revenue-generating company focused on acquiring, developing and commercializing non-opioid pain management products for the treatment of acute and chronic pain and, following the formation of its proposed joint venture with IPMC Company, in neurodegenerative and cardiometabolic disease. Scilex targets indications with high unmet needs and large market opportunities with non-opioid therapies for the treatment of patients with acute and chronic pain and is dedicated to advancing and improving patient outcomes. Scilex’s commercial products include: (i) ZTlido® (lidocaine topical system) 1.8%, a prescription lidocaine topical product approved by the U.S. Food and Drug Administration (the “FDA”) for the relief of neuropathic pain associated with postherpetic neuralgia, which is a form of post-shingles nerve pain; (ii) ELYXYB®, a potential first-line treatment and the only FDA-approved, ready-to-use oral solution for the acute treatment of migraine, with or without aura, in adults; and (iii) Gloperba®, the first and only liquid oral version of the anti-gout medicine colchicine indicated for the prophylaxis of painful gout flares in adults. In addition, Scilex has three product candidates: (i) SP-102 (10 mg, dexamethasone sodium phosphate viscous gel) (“SEMDEXATM” or “SP-102”), a novel, viscous gel formulation of a widely used corticosteroid for epidural injections to treat lumbosacral radicular pain, or sciatica, for which Scilex has completed a Phase 3 study and was granted Fast Track status from the FDA in 2017; (ii) SP-103 (lidocaine topical system) 5.4%, (“SP-103”), a next-generation, triple-strength formulation of ZTlido, for the treatment of acute pain and for which Scilex has recently completed a Phase 2 trial in acute low back pain. SP-103 has been granted Fast Track status from the FDA in low back pain; and (iii) SP-104 (4.5 mg, low-dose naltrexone hydrochloride delayed-release capsules) (“SP-104”), a novel low-dose delayed-release naltrexone hydrochloride being developed for the treatment of fibromyalgia, for which Phase 1 trials were completed in the second quarter of 2022. Scilex Holding Company is headquartered in Palo Alto, California. About Semnur Pharmaceuticals, Inc. Semnur Pharmaceuticals, Inc. (“Semnur”) is a clinical-late stage specialty pharmaceutical company focused on the development and commercialization of novel non-opioid pain therapies. Semnur’s product candidate, SP-102 (SEMDEXA™), is the first non-opioid novel gel formulation administered epidurally in development for patients with moderate to severe chronic radicular pain/sciatica. Semnur Pharmaceuticals, Inc. is headquartered in Palo Alto, California. Forward-Looking Statements This press release and any statements made for and during any presentation or meeting concerning the matters discussed in this press release contain forward-looking statements related to Scilex and its subsidiaries under the safe harbor provisions of Section 21E of the Private Securities Litigation Reform Act of 1995 and are subject to risks and uncertainties that could cause actual results to differ materially from those projected. Forward-looking statements include statements regarding Pain Medicine News published retrospective claims data on ZTlido® vs. lidocaine 5% patch. Risks and uncertainties that could cause Scilex’s actual results to differ materially and adversely from those expressed in our forward-looking statements, include, but are not limited to: risks associated with the Board’s right to change the Record Date and/or revoke the Dividend; Scilex’s ability to consummate a joint venture or any other transaction with IPMC Company and develop and commercialize treatments for obesity, neurodegenerative, cardiometabolic disease; risks associated with the unpredictability of trading markets and whether a market will be established for Scilex’s common stock; general economic, political and business conditions; risks related to COVID-19 (and other similar disruptions); the risk that the potential product candidates that Scilex develops may not progress through clinical development or receive required regulatory approvals within expected timelines or at all; risks relating to uncertainty regarding the regulatory pathway for Scilex’s product candidates; the risk that Scilex will be unable to successfully market or gain market acceptance of its product candidates; the risk that Scilex’s product candidates may not be beneficial to patients or successfully commercialized; the risk that Scilex has overestimated the size of the target patient population, their willingness to try new therapies and the willingness of physicians to prescribe these therapies; risks that the outcome of the trials and studies for SP-102, SP-103 or SP-104 may not be successful or reflect positive outcomes; risks that the prior results of the clinical and investigator-initiated trials of SP-102 (SEMDEXA™), SP-103 or SP-104 may not be replicated; regulatory and intellectual property risks; and other risks and uncertainties indicated from time to time and other risks described in Scilex’s most recent periodic reports filed with the Securities and Exchange Commission, including Scilex’s Annual Report on Form 10-K for the year ended December 31, 2023 and subsequent Quarterly Reports on Form 10-Q that the Company has filed or may file with the SEC, including the risk factors set forth in those filings. Investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this release, and Scilex undertakes no obligation to update any forward-looking statement in this press release except as may be required by law. Contacts: Investors and MediaScilex Holding Company 960 San Antonio RoadPalo Alto, CA 94303Office: (650) 516-4310 Email: investorrelations@scilexholding.com Website: www.scilexholding.com SEMDEXA™ (SP-102) is a trademark owned by Semnur Pharmaceuticals, Inc., a wholly-owned subsidiary of Scilex Holding Company. A proprietary name review by the FDA is planned. ZTlido® is a registered trademark owned by Scilex Pharmaceuticals, Inc., a wholly-owned subsidiary of Scilex Holding Company. Gloperba® is the subject of an exclusive, transferable license to Scilex Holding Company to use the registered trademark. ELYXYB® is a registered trademark owned by Scilex Holding Company. All other trademarks are the property of their respective owners. © 2024 Scilex Holding Company All Rights Reserved.