Delving into the Latest Updates on Levobutylphthalide with Synapse

Chemotherapy-related cognitive Impairment (CICI) is a series of neurocognitive deficits experienced during and after cancer chemotherapy. Studies have reported that CICI affects 25% to 75% of survivors and can persist for years after chemotherapy is discontinued, causing more severe progressive manifestations and placing a heavy burden on families and society. Numerous studies have proposed several potential mechanisms and etiologies for CICI, including direct neurotoxicity, disruption of the blood-brain barrier, reduced hippocampal neurogenesis, white matter abnormalities, secondary neuroinflammatory responses, and increased oxidative stress. At present, there is no clear and effective diagnosis and therapy for CICI, and how to diagnose and treat cognitive impairment caused by chemotherapy effectively is still the focus and difficulty.
Based on the previous consensus on the application of dl-3-n-butylphthalide, butylphthalein can play a neuroprotective role by reducing oxidative stress and inflammatory response, inhibiting neuronal apoptosis, improving mitochondrial function and other mechanisms, and significantly improve the performance of the central nervous system caused by cerebral ischemia and vascular dementia. However, the increase of neuroinflammatory response and oxidative stress is precisely one of the potential mechanisms of CICI pathogenesis. Therefore, based on the above findings, this study hypothesized that dl-3-n-butylphthalide would also have considerable efficacy in the treatment of CICI.

Start Date01 Jul 2024

Sponsor / Collaborator

The First Hospital Of China Medical University

NCT05976152

/ RecruitingPhase 3IIT

Effect of Butyphthalide on Cognitive Level Change After Cerebral Vascular Event-a Randomized Control Trial (Be-CLEVER)

Post-stroke cognitive impairment (PSCI) refers to a clinical syndrome characterized by cognitive impairment that occurs after a stroke event and persists for at least 24 weeks. Due to the early recovery of conditions such as delirium and transient cognitive impairment after stroke, the diagnosis of PSCI often requires cognitive assessment at 12 to 24 weeks post-stroke to determine the severity of cognitive impairment. It can be classified according to the severity of cognitive impairment as post-stroke cognitive impairment no dementia (PSCIND) and post-stroke dementia (PSD). Recent large international cohort studies have reported an incidence rate of PSCI ranging from 24% to 53.4%, and patients with PSCI have a significantly higher mortality rate compared to those without cognitive impairment. Guidelines such as American Heart Association/American Society of Anesthesiologists (AHA/ASA) and the Chinese "Expert Consensus on the Management of Post-Stroke Cognitive Impairment" propose integrating cognitive impairment and stroke intervention strategies. Early comprehensive intervention and treatment for high-risk individuals after stroke, aiming to delay or prevent the progression from PSCIND to PSD, are the primary goals in the current treatment of PSCI. However, there is currently a lack of large randomized controlled trials (RCTs) for PSCI, and research is still needed to determine whether cognitive-enhancing drugs can reduce the risk of PSCI occurrence and improve outcomes and prognosis for PSCI patients. A randomized, double-blind, multicenter clinical study involving 281 non-dementia vascular cognitive impairment (VCI) patients showed that the overall cognitive scores of patients treated with donepezil for 24 weeks significantly improved compared to the placebo group.
The aim of this study is to evaluate the effectiveness of donepezil in the treatment of post-stroke cognitive impairment. It will be a multicenter, randomized, double-blind, placebo-controlled trial with a 48-week treatment duration. The study will observe the difference in PSCI incidence rate between the donepezil treatment group and the conventional stroke treatment group at 24 weeks and evaluate the improvement in post-stroke cognitive impairment after 6 months of donepezil treatment compared to conventional treatment.
This study will be conducted in two stages: the first stage (0-24 weeks) aims to assess whether donepezil can reduce the risk of PSCI occurrence and will be a multicenter, randomized, double-blind, placebo-controlled study. The second stage (24-48 weeks) aims to evaluate whether donepezil can improve the prognosis of PSCI patients and will also be a multicenter, randomized, double-blind, placebo-controlled study.

Start Date01 Apr 2024

Sponsor / Collaborator

Fudan University

NCT04675450

/ WithdrawnPhase 2

A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of n-Butylphthalide (NBP) Softgel Capsules Administered to Patients With Metastatic Breast Cancer to Prevent Nab-paclitaxel Induced Toxic Neuropathy

Phase 2, randomized, double-blind, Placebo-Controlled, Multiple Dose Study for the treatment of Patients with Metastatic Breast Cancer.

Start Date30 Jun 2023

Sponsor / Collaborator

Conjupro Biotherapeutics, Inc.

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100 Clinical Results associated with Levobutylphthalide

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100 Translational Medicine associated with Levobutylphthalide

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100 Patents (Medical) associated with Levobutylphthalide

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633

Literatures (Medical) associated with Levobutylphthalide

01 Jun 2025·Brain Research Bulletin

DL-3-n-butylphthalide inhibits astrocyte activation in the cortical penumbra of ischemia-reperfusion model rats via AKT signaling

Article

Author: Ji, Yifei ; Li, Biao ; Li, Qiuling ; Xiao, Yu ; Yu, Yiwen ; Wang, Shan ; Dong, Fei ; Wang, Tinghong ; Zhao, Hao ; Lei, Dong

Ischemic stroke triggers rapid activation of astrocytes, which contributes to tissue damage. Dl-3-n-butylphthalide (NBP), an independently developed compound in China for the treatment of ischemic stroke, has unclear molecular mechanisms. In this study, we established a Sprague-Dawley rat model of middle cerebral artery occlusion (MCAO) by occluding the middle cerebral artery for 1.5 h followed by reperfusion for 72 h. We assessed neurological scores, infarct volume, neuronal injury, and the expression levels of GFAP, C3, S100A10, GLT-1, p-AKT/AKT, and p-mTOR/mTOR, as well as immunofluorescence double staining of C3/S100A10 with GFAP and GLT-1 respectively. NBP significantly improved neurological function in MCAO rats, reduced infarct area, alleviated neuronal injury, inhibited A1 astrocyte polarization, promoted A2 astrocyte polarization, and upregulated GLT-1 expression. However, the AKT inhibitor (TCN) weakened NBP's regulatory effects on astrocytes and GLT-1. Finally, immunofluorescence experiments showed that GLT-1 colocalized more effectively with A2 astrocytes than with A1 astrocytes. We demonstrated that NBP reduces astrocyte activation and upregulates GLT-1 expression via the AKT/mTOR pathway, providing new insights into therapeutic strategies for ischemic stroke and valuable clues for drug design.

01 Jun 2025·European Journal of Medicinal Chemistry

A brain-targeting dl-3-n-butylphthalide prodrug to treat ischemic stroke

Article

Author: Huang, Shiqi ; Han, Yikun ; Lin, Qing ; Zhang, Ling ; Zhang, Qiang ; Zhang, Zhirong ; Zhou, Shuhao ; Zhang, Yicong ; Zhang, Hanming ; Xiang, Honglin

Stroke is an acute cerebrovascular disease worldwide, featured by stubbornly high mortality and morbidity. 3-n-butylphthalide (NBP) is a first-line agent to treat ischemic stroke, but its unsatisfactorily intracephalic bioavailability is detrimental to the therapeutic efficacy. We have previously developed a series of prodrugs analogous to NBP, however, their conversion rate in the targeted sites cannot meet the clinical demand. Hence, it is imperative to ameliorate the bioavailability and cellular uptake efficiency of the prodrugs, which may be driven by potential energy consuming cationic transporters. Accordingly, we fabricated a novel prodrug named DB-10, which were used tertiary amine to possess active targeting capacity and connected through amide bonds. Moreover, it is noteworthy that DB-10 could rapidly convert into active original drug in the brain to treat acute injury caused by ischemia-reperfusion (I/R). The cytotoxicity of DB-10 was equivalent to that of NBP and would not cause obviously undesired damage in vivo. These encouraging results demonstrate that DB-10 could easily increase the accumulation in the brain site, and significantly improve the treatment effect for ischemic stroke, indicating this biosafety prodrug holds tremendous potential for clinical application prospects.

01 May 2025·International Journal of Biological Macromolecules

Effects of Ganoderma lucidum fermentation on the structure of Tartary buckwheat polysaccharide and its impact on gut microbiota composition

Article

Author: Chen, Hongyan ; Zeng, Xuefeng ; Hu, Wenkang ; Tan, Fuyao ; Hui, Fuyi ; Zou, Shiping ; Da, Ziru ; Cen, Qin ; Zhang, Rui

Fermentation modifies plant polysaccharides and enhances their bioactivity. In this study, polysaccharides were extracted from Ganoderma lucidum-fermented (FBP) and non-fermented (NBP) Tartary buckwheat. The structure of the polysaccharides and their effects on gut microbial composition were explored. According to the results, the molecular weight of FBP lowered from 8.86 × 10⁵ Da to 3.83 × 10⁴ Da, the fermentation process produced fucose (7.72 %) and mannose (6.68 %), and the content of glucose and galactose increased. Compared with NBP, FBP showed a significant increase in solubility, crystallinity and thermal stability, while there was a decrease in apparent viscosity. The in vitro fecal fermentation results suggested that FBP promoted the production of short-chain fatty acids, with acetic acid, propionic acid and butyric acid being the main metabolites. FBP and NBP dramatically decreased the relative abundance of Escherichia-Shigella. FBP increased the relative abundances of Bacteroides, Parabacteroides, and Megamonas, while NBP increased those of Bifidobacterium and Phascolarctobacterium. Finally, further analysis of functional prediction indicated that carbohydrate metabolism, lipid metabolism and cardiovascular disease were the most vital pathways for FBP to promote health. This study offers some theoretical foundation for the chemical structure and regulation of gut microbiota by Ganoderma lucidum fermented buckwheat modified polysaccharides.

100 Deals associated with Levobutylphthalide

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Metastatic breast cancer	Phase 2	-	CSPC NBP Pharmaceutical Co., Ltd.	30 Jun 2023
Metastatic breast cancer	Phase 2	-	Conjupro Biotherapeutics, Inc.	30 Jun 2023
Peripheral Nervous System Diseases	Phase 2	-	Conjupro Biotherapeutics, Inc.	30 Jun 2023
Peripheral Nervous System Diseases	Phase 2	-	CSPC NBP Pharmaceutical Co., Ltd.	30 Jun 2023
Alzheimer Disease	Preclinical	China	Xuanwu Hospital Capital Medical University	16 Jun 2023
Acute Ischemic Stroke	Preclinical	United States	CSPC NBP Pharmaceutical Co., Ltd.	28 Feb 2018
Stroke	Preclinical	China	CSPC Zhongqi Pharmaceutical Technology Shijiazhuang Co., Ltd.	17 Feb 2005

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


Pubmed Manual	Not Applicable	Aphasia	118	DL-3-N-butylphthalide (NBP) soft capsules	hdzycilueo(rswgmtgtvu): Difference (Mean) = 0.106 (95% CI, 0.018 - 0.195), P-Value = 0.003 View more	Positive	22 Nov 2024
				Placebo