Efficacy and Safety of MT10107 (Coretox) in Poststroke Upper Limb Spasticity Treatment: A Randomized, Double-Blind, Active Drug-Controlled, Multicenter, Phase III Clinical Trial

Lee, Junekyung; Chun, Min Ho; Ko, Young Jin; Lee, Shi-Uk; Kim, Deog Young; Paik, Nam–Jong; Kwon, Bum Sun; Park, Yoon Ghil

doi:10.1016/j.apmr.2020.03.025

Cited by 6 publications

(6 citation statements)

References 22 publications

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“…As a result, 0.06 and 0.12 mg/kg were selected as the dose of HSA. The dose of polysorbate 20 was selected based on the content of polysorbate 20 in COR-ETOX 1 (1.0 mg/vial, 60 kg human) and the human dosage of CORETOX 1 (0.2~3.6 vial) [12,13]. The dose of polysorbate 20 was also calculated in the same manner and 0.02, 0.1, and 0.4 mg/kg were selected as the dose of polysorbate 20.…”

Section: Animals and Facilitymentioning

confidence: 99%

“…All substances were injected once every two weeks for four weeks (a total of 3 times; days 1, 15, 29) into one site of the gastrocnemius muscle of the right hindlimb. The dosing schedule (interval and frequency) was set based on the clinical application schedule (total 1 time, at least three month dosing interval) and the administration site (gastrocnemius muscle) was selected based on the site generally used to evaluate the effectiveness of BoNT/A in rodents [12,[21][22][23].…”

Section: In Vivo Administrationmentioning

confidence: 99%

“…In particular, as a food additive, polysorbate 20 has various in vivo safety data, including in vitro genotoxicity and DNA reactivity based on structural alerts [26]. Recently, polysorbate 20, which was one of the excipients of CORETOX 1 approved by the Ministry of Food and Drug Safety (MFDS, Republic of Korea), has been used in humans via an intramuscular route of administration [12]. However, there are few studies on the safety of polysorbate 20 when administered intramuscularly.…”

Section: Plos Onementioning

confidence: 99%

“…To evaluate the systemic toxicity of intramuscular injection of polysorbate 20, a four-week repeated dose toxicity study in SD rats was conducted. According to the MFDS, the clinical dosage of CORETOX 1 , which contains 1 mg of polysorbate 20 in one vial, ranged from 0.2 mg/kg, male; j) Human serum albumin-0.06 mg/kg, female; k) Human serum albumin-0.12 mg/kg, male; l) Human vial (treatment of forehead wrinkles) to 3.6 vials (stiff muscles in the upper limbs after a stroke) [12]. Thus, the dose (0.02, 0.1, and 0.4 mg/kg) of polysorbate 20 in the current study was established based on the therapeutic indication of CORETOX 1 in humans and the animal equivalent dose calculation factor [19].…”

Section: Plos Onementioning

confidence: 99%

“…For those reasons, Medytox, Inc. (Republic of Korea) has recently developed a complexing protein-free BoNT/A product (CORETOX 1 ) that uses polysorbate 20, a non-human-derived excipient, to replace the HSA [12,13]. Polysorbates, a series of polyoxyethylenated sorbitan esters, are hydrophilic and nonionic surfactants that have been widely used as a food additive and stabilizer in pharmaceuticals [14,15].…”

Section: Introductionmentioning

confidence: 99%

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Safety verification for polysorbate 20, pharmaceutical excipient for intramuscular administration, in Sprague-Dawley rats and New Zealand White rabbits

Kim¹,

Kwak

Park³

et al. 2021

PLoS ONE

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Human serum albumin (HSA) has been widely used as a pharmaceutical excipient in Botulinum toxin serotype A (BoNT/A) products that are indicated for use in therapeutics and cosmetics. However, HSA as a human-derived material has some concerns, such as the potential risk of transmission of infectious agents, an insufficient supply, and difficulty in maintaining a certain quality. For those reasons, newly developed BoNT/A products (CORETOX®, Medytox, Inc., Republic of Korea) contained polysorbate 20, a non-human-derived excipient, to replace the HSA. However, most safety studies of polysorbate 20 have been conducted with non-invasive routes of administration, and thus there are a few studies on the safety of polysorbate 20 when administered intramuscularly. To secure the in vivo safety profile of polysorbate 20, a four-week repeated intramuscular dose toxicity study (0.02, 0.1, and 0.4 mg/kg, one injection every two weeks for a total of three injections) was conducted in 66 Sprague-Dawley (SD) rats. An intradermal irritation study was further conducted with 18 New Zealand White (NZW) rabbits. The toxicological evaluation of HSA (0.06 and 0.12 mg/kg) was also carried out as a comparative substance. Systemic and local toxicities were not observed in any of the SD rats or NZW rabbits based on clinical signs, body weight, hematology, clinical biochemistry, macroscopic findings on necropsy, histopathology of the injection site, and allergic reactions. The current study suggested that intramuscular administration of polysorbate 20 was considered to be safe at a level similar to that of HSA, which has an in vivo safety profile accumulated over the years. This provided the basis for the in vivo safety profile of polysorbate 20 administered intramuscularly and the scientific reliability of the use of polysorbate 20 as an alternative to HSA, which is used as an excipient for various pharmaceuticals in terms of its safety.

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Section: Animals and Facilitymentioning

confidence: 99%

Section: In Vivo Administrationmentioning

confidence: 99%

Section: Plos Onementioning

confidence: 99%

Section: Plos Onementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Safety verification for polysorbate 20, pharmaceutical excipient for intramuscular administration, in Sprague-Dawley rats and New Zealand White rabbits

Kim¹,

Kwak

Park³

et al. 2021

PLoS ONE

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Soft Upper‐Limb Wearable Robotic Devices: Technology and Applications

Sharma,

Phan,

Davies

et al. 2024

Advanced Intelligent Systems

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One of the practical applications in the field of soft robotics involves the development of soft robotic wearable devices. These devices make use of their intrinsically compliant structures to interact safely and harmoniously with the human body. While soft wearable robots demonstrate their utility in lower‐limb applications for locomotion, the upper‐limb domain offers significant prospects in a wide range of applications that soft robotic technology can address. In this review, the current state of technology in the field of soft wearable upper limbs is systematically analyzed and categorized. Categorizations are made based on their applications in rehabilitation, activities of daily living support, and human augmentation. Furthermore, in this study, also contemporary technological aspects, encompassing sensing technology and control systems, are explored. Despite exciting potential in this domain, several limitations from existing devices inherently impede widespread adoption and thus hinder further progress in the field. In this study, also an overview of the different facets of the domain is provided and key considerations for the advancement of soft wearable robotic devices intended for upper‐limb applications are prescribed.

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Dissociation mechanics and stability of type A botulinum neurotoxin complex by means of biophysical evaluation

Hada

Lee

et al. 2022

J. Pharm. Investig.

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Biophysical characterization of type A botulinum neurotoxin (BoNT/A) complex along with its thermodynamic stability was assessed through a combination of various methods. BoNT/A exists as large complexes in association with neurotoxin associated proteins (NAPs). To evaluate its biophysical behavior, size-exclusion chromatography (SEC), multi-angled light scattering (MALS), enzyme linked immunosorbent assay (ELISA), and dynamic light scattering (DLS) were utilized. Initially, a single peak (peak 1) of SEC was observed at pH 6.0, and an additional peak (peak 2) appeared at pH 7.4 with a decrement of peak 1. Through MALS and ELISA, the peak 2 was determined to be BoNT/A dissociated from its complex. The dissociation was accelerated by time and temperature. At 37°C, dissociated BoNT/A self-associated at pH 7.4 in the presence of polysorbate 20. On the other hand, the dissociation was partly reversible when titrated back to pH 6.0. Overall, BoNT/A was more stable when associated with NAPs at pH 6.0 compared to its dissociated state at pH 7.4. The conventional analytical methods could be utilized to relatively quantify its amount in different formulations.

show abstract

Efficacy and Safety of MT10107 (Coretox) in Poststroke Upper Limb Spasticity Treatment: A Randomized, Double-Blind, Active Drug-Controlled, Multicenter, Phase III Clinical Trial

Cited by 6 publications

References 22 publications

Safety verification for polysorbate 20, pharmaceutical excipient for intramuscular administration, in Sprague-Dawley rats and New Zealand White rabbits

Safety verification for polysorbate 20, pharmaceutical excipient for intramuscular administration, in Sprague-Dawley rats and New Zealand White rabbits

Soft Upper‐Limb Wearable Robotic Devices: Technology and Applications

Dissociation mechanics and stability of type A botulinum neurotoxin complex by means of biophysical evaluation

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