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新型无神经毒素相关蛋白的肉毒毒素 A 的动态肌肉麻痹作用。

Dynamic muscle paralytic effects of a novel botulinum toxin A free of neurotoxin-associated proteins.

机构信息

Shanghai YangZhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), School of Medicine, Tongji University, Shanghai, China.

Department of Neurology, Shanghai Tongji Hospital, School of Medicine, Tongji University, Shanghai, China.

出版信息

Pharmacol Res Perspect. 2022 Jun;10(3):e00955. doi: 10.1002/prp2.955.

DOI:10.1002/prp2.955
PMID:35484714
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9051373/
Abstract

Structurally, botulinum toxin type A (BTX-A) is composed of neurotoxin and nontoxic complexing proteins (CPs), and the neurotoxin has the function of blocking acetylcholine release from the neuromuscular junction and therefore paralyzing muscles. Nowadays, a novel botulinum toxin A free of CPs (chinbotulinumtoxin A, A/Chin) is produced, and the present study comprehensively evaluated the dynamic paralytic effect of A/Chin on the gastrocnemius muscle of rats. Different doses (0.01, 0.1, 0.5, 1, 2, and 4 U) of A/Chin and other BTX-As with and without CPs were administered to the gastrocnemius muscles of rats and muscle strength was measured and compared at different postinjection timepoints (from day 0 to 84). With the dose increased, time-to-peak paralytic effect of other BTX-As varied from day 3 to day 14, while A/Chin groups showed rapid and steady time to peak on day 3. At the lowest dose of 0.01 U, A/Chin showed significantly better peak paralytic effect than the others on day 3. When the dose increased to 0.5 U and more, A/Chin group also showed significant paralytic effect when the paralytic effect of other BTX-As was worn off. Moreover, the paralytic effect of A/Chin was confirmed as muscle atrophy while hematoxylin-eosin staining was performed. In conclusion, compared with other BTX-As, A/Chin showed rapid and steady time-to-peak paralytic effect and long-term paralytic efficacy at the same dose level. And it might lay a solid foundation for further wide application of A/Chin in both clinical and cosmetic areas.

摘要

从结构上看,A型肉毒毒素(BTX-A)由神经毒素和非毒性复合蛋白(CP)组成,神经毒素具有阻止乙酰胆碱从运动终板释放的功能,从而使肌肉瘫痪。如今,一种新型的不含 CP 的肉毒毒素 A( chinbotulinumtoxin A,A/Chin)被生产出来,本研究全面评估了 A/Chin 对大鼠腓肠肌的动态麻痹作用。不同剂量(0.01、0.1、0.5、1、2 和 4 U)的 A/Chin 和其他含或不含 CP 的 BTX-A 被注射到大鼠的腓肠肌中,并在不同的注射后时间点(从第 0 天到第 84 天)测量和比较肌肉力量。随着剂量的增加,其他 BTX-A 的起效时间从第 3 天到第 14 天不等,而 A/Chin 组在第 3 天表现出快速而稳定的起效时间。在最低剂量 0.01 U 时,A/Chin 在第 3 天的峰值麻痹效果明显优于其他药物。当剂量增加到 0.5 U 及以上时,当其他 BTX-A 的麻痹作用消退时,A/Chin 组也表现出显著的麻痹作用。此外,通过进行苏木精-伊红染色证实了 A/Chin 的麻痹作用是肌肉萎缩。总之,与其他 BTX-A 相比,A/Chin 在相同的剂量水平下表现出快速而稳定的起效时间和长期的麻痹效果。这为进一步广泛应用 A/Chin 在临床和美容领域奠定了坚实的基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34ef/9051373/c70027e48122/PRP2-10-e00955-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34ef/9051373/6bdd52fa853f/PRP2-10-e00955-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34ef/9051373/848100622d73/PRP2-10-e00955-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34ef/9051373/c70027e48122/PRP2-10-e00955-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34ef/9051373/6bdd52fa853f/PRP2-10-e00955-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34ef/9051373/848100622d73/PRP2-10-e00955-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34ef/9051373/c70027e48122/PRP2-10-e00955-g004.jpg

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Toxins (Basel). 2022 Jan 6;14(1):44. doi: 10.3390/toxins14010044.
2
Alternative Clinical Indications of Botulinum Toxin.肉毒毒素的其他临床适应证。
Am J Clin Dermatol. 2020 Dec;21(6):855-880. doi: 10.1007/s40257-020-00532-0.
3
OnabotulinumtoxinA Displays Greater Biological Activity Compared to IncobotulinumtoxinA, Demonstrating Non-Interchangeability in Both In Vitro and In Vivo Assays.
A型肉毒毒素的生物学活性大于注射用A型肉毒梭菌神经毒素,在体外和体内检测中均显示不可互换性。
Toxins (Basel). 2020 Jun 13;12(6):393. doi: 10.3390/toxins12060393.
4
Frequency and risk factors of antibody-induced secondary failure of botulinum neurotoxin therapy.肉毒毒素治疗抗体诱导的继发性失败的频率和危险因素。
Neurology. 2020 May 19;94(20):e2109-e2120. doi: 10.1212/WNL.0000000000009444. Epub 2020 Apr 24.
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Comparative Pharmacodynamics Study of 3 Different Botulinum Toxin Type A Preparations in Mice.比较 3 种不同的 A 型肉毒毒素制剂在小鼠体内的药效动力学研究。
Dermatol Surg. 2020 Dec;46(12):e132-e138. doi: 10.1097/DSS.0000000000002402.
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