更新于：2024-04-26
Busulfan
白消安
更新于：2024-04-26
概要
基本信息
最高研发阶段批准上市 |
首次获批日期 美国 (1954-06-26), |
最高研发阶段(中国)批准上市 |
特殊审评孤儿药 (美国) |
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结构
分子式C6H14O6S2 |
InChIKeyCOVZYZSDYWQREU-UHFFFAOYSA-N |
CAS号55-98-1 |
关联
550
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Pre-transplant Purging and Post-transplant MRD-guided Maintenance Therapy With Elranatamab in Patients With High-risk Multiple Myeloma
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100 项与 白消安 相关的专利（医药）
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6,295
项与 白消安 相关的文献（医药）2024-04-01Journal of Ethnopharmacology
Study on the effects and mechanisms of Wenzhong Bushen Formula in improving ovarian reserve decline in mice based on network pharmacology
Article
作者: Chen, Keming ; Xie, Haibo ; Liu, Feifei ; Chen, Hua ; Peng, Qingjie ; Li, Guangyong ; Liang, Xiaoxia ; He, Rui ; Du, Xiaoli ; Ouyang, Jiahui ; Chen, Xiaojiang ; Zhu, Xiangdong ; Yu, Leyi
ETHNOPHARMACOLOGICAL RELEVANCE:
The Wenzhong Bushen Formula (WZBSF) is a traditional Chinese medicine empirical formula known for its effects in tonifying qi, strengthening the spleen, warming the kidneys, promoting yang, regulating blood circulation, and balancing menstruation. Clinical evidence has demonstrated its significant efficacy in treating Diminished Ovarian Reserve (DOR) by improving ovarian reserves. However, the specific pharmacological mechanisms of WZBSF remain unclear.
AIM OF THE STUDY:
This study aims to investigate the mechanisms by which WZBSF improves ovarian reserve decline through network pharmacology and animal experiments.
METHODS AND MATERIALS:
WZBSF was analyzed using a dual UPLC-MS/MS and GC-MS platform. Effective components and targets of WZBSF were obtained from the TCMSP database and standardized using UniProt. Disease targets were collected from GeneCard, OMIM, PHARMGKB, and DisGeNET databases, with cross-referencing between the two sets of targets. A PPI protein interaction network was constructed using Cytoscape3.9.1 and STRING database, followed by KEGG and GO enrichment analysis using the Metascape database. Finally, an ovarian reserve decline model was established in mice, different doses of WZBSF were administered, and experimental validation was conducted through serum hormone detection, H&E staining, immunofluorescence (IF), immunohistochemistry (IHC), and Western blot analysis (WB).
RESULTS:
WZBSF shares 145 common targets with ovarian reserve decline. GO enrichment analysis revealed involvement in biological processes such as response to hormone stimulation and phosphatase binding, while KEGG analysis implicated pathways including the PI3K-AKT signaling pathway and FoxO signaling pathway. In mice with ovarian reserve decline, WZBSF restored weight gain rate, increased ovarian index, normalized estrous cycles, reversed serum hormone imbalances, restored various follicle counts, and improved ovarian morphology. Additionally, WZBSF reduced p-AKT and p-FOXO3a levels, preventing excessive activation of primordial follicles and maintaining ovarian reserve.
CONCLUSION:
WZBSF can ameliorate cyclophosphamide and busulfan-induced ovarian reserve decline, and its mechanism may be associated with the inhibition of the PI3K/AKT/FOXO3a signaling pathway.
2024-03-01Ecotoxicology and Environmental Safety
Exosomes derived from umbilical cord mesenchymal stem cells ameliorate male infertility caused by busulfan in vivo and in vitro
Article
作者: Wang, Fang ; Yang, Ruifeng ; Xiong, Chengliang ; Han, Ying ; Yue, Dezhi
Environmental pollution has emerged as a global concern due to its detrimental effects on human health. One of the critical aspects of this concern is the impact of environmental pollution on sperm quality in males. Male factor infertility accounts for approximately 40%- 50% of all infertility cases. Nonobstructive azoospermia (NOA) is the most severe type of male infertility. Human umbilical cord mesenchymal stem cell (hUCMSC) exosomes enhance proliferation and migration, playing crucial roles in tissue and organ injury repair. However, whether hUCMSC exosomes impacting on NOA caused by chemotherapeutic agents remains unknown. This study aimed to explore the functional restoration and mechanism of hUCMSC exosomes on busulfan-induced injury in GC-1 spg cells and ICR mouse testes. Our results revealed that hUCMSC exosomes effectively promoted the proliferation and migration of busulfan-treated GC-1 spg cells. Additionally, oxidative stress and apoptosis were significantly reduced when hUCMSC exosomes were treated. Furthermore, the injection of hUCMSC exosomes into the testes of ICR mice treated with busulfan upregulated the expression of mouse germ cell-specific genes, such as vasa, miwi, Stra8 and Dazl. Moreover, the expression of cellular junction- and cytoskeleton-related genes, including connexin 43, ICAM-1, β-catenin and androgen receptor (AR), was increased in the testicular tissues treated with exosomes. Western blot analysis demonstrated significant downregulation of apoptosis-associated proteins, such as bax and caspase-3, and upregulation of bcl-2 in the mouse testicular tissues injected with hUCMSC exosomes. Further, the spermatogenesis in the experimental group of mice injected with exosomes showed partial restoration of spermatogenesis compared to the busulfan-treated group. Collectively, these findings provide evidence for the potential clinical applications of hUCMSC exosomes in cell repair and open up new avenues for the clinical treatment of NOA.
2024-03-01Journal of Ethnopharmacology
Kuntai capsule attenuates premature ovarian insufficiency by activating the FOXO3/SIRT5 signaling pathway in mice: A comprehensive study using UHPLC-LTQ-Orbitrap and integrated pharmacology
Article
作者: Yang, Hongjun ; Wang, Lan ; Zhang, Xueyan ; Hou, Jinli ; Yin, Xiaojie ; Yin, Chenghong ; Gong, Leilei ; Zhao, Jingxia ; Feng, Xin
ETHNOPHARMACOLOGICAL RELEVANCE:
Classical prescriptions are not only a primary method of clinical treatment in traditional Chinese medicine (TCM) but also represent breakthroughs in the inheritance and development of this field. Kuntai capsule (KTC), a formulation based on a classical prescription, comprises six TCMs: Rehmanniae Radix Praeparata, Coptidis Rhizoma, Paeoniae Radix Alba, Scutellariae Radix, Asini Corii Colla, and Poria. This formulation possesses various beneficial effects, such as nourishing yin and blood, clearing heat and purging fire, and calming the nerves and relieving annoyance. The investigation of the efficacy and mechanism of KTC in regulating anti-aging factors in the treatment of premature ovarian insufficiency (POI) is not only a prominent topic in classical prescription research but also a crucial issue in the treatment of female reproductive aging using TCM.
AIM OF THE STUDY:
To evaluate the therapeutic effect of KTC on POI and its underlying mechanism.
MATERIALS AND METHODS:
Healthy and specific pathogen-free (SPF) female Kunming mice aged 6-8 weeks were selected. After acclimatization, the mice were randomly divided into a control, model, and high, middle, and low dose groups of KTC (1.6, 0.8, and 0.4 mg/kg, respectively). Except for the control group, the animals in the other groups were administered a single intraperitoneal injection of 120 mg/kg cyclophosphamide and 30 mg/kg Busulfan to induce the model of POI. After modeling, the mice were treated with the corresponding drugs for 7 days. Serum and ovarian tissues were collected, and the levels of serum follicle-stimulating hormone (FSH), estradiol (E2), and superoxide dismutase 2 (SOD2) were determined using enzyme-linked immunosorbent assay (ELISA). The chemical composition of KTC was characterized and analyzed using ultra-high-pressure liquid chromatography-linear ion trap-Orbitrap tandem mass spectrometry. A "drug-component-target-pathway-disease" network was constructed using network pharmacology research methods to identify the key active components of KTC in treating POI and to elucidate its potential mechanism. The protein expression of the FOXO3/SIRT5 pathway was detected by western blotting.
RESULTS:
Compared to the model group, the high-dose group of KTC showed a significant increase in ovarian index, significant increase in levels of E2 and SOD2, and a significant decrease in FSH levels. Through systematic analysis of the chemical constituents of KTC, 69 compounds were identified, including 7 organic acids, 14 alkaloids, 28 flavonoids, 15 terpenoids, 2 lignans, 2 phenylpropanoids, and 1 sugar. Based on network pharmacology research methods, it was determined that KTC exerts its therapeutic effect on POI through multiple components (paeoniflorin and malic acid), multiple targets (FOXO3 and SIRT5), and multiple pathways (prolactin signaling pathway, longevity regulating pathway, and metabolic pathways). The accuracy of the network pharmacology prediction was further validated by detecting the protein expression of SIRT5 and FOXO3a, which showed a significant increase in the middle and high-dose groups of KTC compared to the model group.
CONCLUSIONS:
KTC may effectively treat POI through a multi-component, multi-target, multi-pathway approach, providing an experimental basis for using KTC based on classical prescriptions in the treatment of POI.
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研发状态
| 适应症 | 最高研发状态 | 国家/地区 | 公司 |
|---|---|---|---|
| 费城染色体阳性慢性粒细胞白血病 | 批准上市 | 美国 更多 | |
| 造血干细胞移植 | 批准上市 | 列支敦士登 更多 | |
| 骨髓移植排斥反应 | 批准上市 | 日本 更多 | |
| 弥漫性大B细胞淋巴瘤 | 终止 | - | |
| 多发性骨髓瘤 | 无进展 | 加拿大 更多 |
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临床结果
临床结果
适应症
分期
评价
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临床2期 | 61 | Umbilical Cord Blood Transplantation+Fludarabine Phosphate+Busulfan+CYCLOPHOSPHAMIDE+Melphalan+Tacrolimus+Ruxolitinib+mycophenolate mofetil+Methotrexate | 範構醖鹽夢糧網築積襯(淵願範選齋齋網窪蓋艱) = 膚廠襯積選糧衊蓋構壓 積廠遞壓製蓋艱膚艱壓 (醖醖鹽構積壓鏇鬱廠獵, 壓構願醖蓋觸窪廠遞蓋 ~ 餘築鹽製壓鬱襯構鏇壓) 更多 | - | 2024-03-05 | ||
临床2/3期 | 12 | 鬱鹽窪觸鹽齋鹽鏇壓齋(廠衊製衊艱糧糧艱簾衊) = 構繭築顧範遞鹹壓夢積 淵築獵鏇顧鏇鏇顧網製 (築齋簾網夢願憲鹽壓糧, 餘艱網鏇範廠醖遞製壓 ~ 遞蓋憲獵網衊鹽範網衊) 更多 | - | 2024-01-29 | |||
临床2期 | 11 | (Matched Sibling Donor Group) | 餘齋鑰衊網繭餘夢夢膚(膚顧艱構構鬱衊顧鹹獵) = 鹹選餘廠鑰壓構鹽壓壓 鹽憲鬱觸鏇繭遞繭艱窪 (憲範鏇鑰餘遞齋衊繭憲, 構憲顧憲憲蓋壓鑰製築 ~ 艱鬱窪網製夢齋願蓋壓) 更多 | - | 2024-01-17 | ||
Stem Cell Infusion+Clofarabine+Fludarabine+Busulfan+Cyclophosphamide+Decitabine+Tacrolimus+mycophenolate mofetil+cytarabine+Idarubicin (Haploidentical Donor Group) | 餘齋鑰衊網繭餘夢夢膚(膚顧艱構構鬱衊顧鹹獵) = 鏇鬱壓醖艱範簾願蓋淵 鹽憲鬱觸鏇繭遞繭艱窪 (憲範鏇鑰餘遞齋衊繭憲, 鬱夢築餘齋淵網襯構網 ~ 築鬱淵膚壓衊膚艱製廠) 更多 | ||||||
N/A | 536 | 製廠願構襯繭夢膚範積(簾構壓觸齋繭壓繭繭網): HR = 0.61 (95% CI, 0.39 ~ 0.93) 更多 | - | 2023-12-10 | |||
N/A | 40 | 憲膚齋窪觸衊膚選鏇餘(糧遞窪醖壓網衊鬱膚願) = 網鏇製築壓淵積積鬱願 餘網壓獵構積範廠製鬱 (夢繭淵構構齋壓餘築顧, 艱願遞蓋齋顧憲積鏇選 ~ 膚選鹽積淵餘膚選積繭) 更多 | - | 2023-10-30 | |||
临床2期 | 60 | 窪憲製憲餘顧鹹膚艱構(艱壓遞夢獵獵憲觸觸襯) = 築顧鏇選淵襯壓繭醖窪 鹹鏇製觸襯構簾顧顧築 (顧製膚製鹹憲艱餘願壓, 壓鑰糧繭願鬱範鬱鏇夢 ~ 艱繭艱蓋衊鏇獵範蓋範) 更多 | - | 2023-10-27 | |||
临床2期 | 27 | allogeneic hematopoietic stem cell transplantation+fludarabine phosphate+Busulfan+Cyclophosphamide+Tacrolimus+mycophenolate mofetil | 築餘選構網範醖築網築(觸觸網觸選網網艱鏇蓋) = 簾鏇鏇製範憲築遞顧築 獵範襯顧淵淵壓製鏇醖 (醖觸構遞選獵餘觸獵積, 鏇觸窪遞鏇繭蓋襯窪鬱 ~ 積廠鏇壓網鹹範範壓醖) 更多 | - | 2023-10-11 | ||
N/A | - | 221 | 網遞範餘憲壓壓選範窪(糧積簾壓鬱觸觸餘膚鏇) = 鬱積鏇醖蓋齋衊襯糧窪 鹹齋蓋艱艱夢積製簾觸 (齋憲鹹廠窪積範窪餘膚 ) 更多 | - | 2023-09-26 | ||
High-dose melphalan | 網遞範餘憲壓壓選範窪(糧積簾壓鬱觸觸餘膚鏇) = 膚鬱鏇鏇衊齋醖獵繭顧 鹹齋蓋艱艱夢積製簾觸 (齋憲鹹廠窪積範窪餘膚 ) 更多 | ||||||
临床2期 | 2 | Granulocyte colony-stimulating factor+Clofarabine+Fludarabine+Busulfan+Cyclophosphamide+Tacrolimus+Cellcept | 壓餘憲構膚襯夢夢遞積(構遞蓋繭齋鏇願廠壓範) = 鹽淵衊觸顧艱遞範醖壓 襯衊餘壓蓋壓醖構淵窪 (廠鹹廠襯鏇鹹蓋鬱襯願, 遞鹹窪蓋網範糧鏇範範 ~ 網鏇鑰獵鏇願窪選範鑰) 更多 | - | 2023-09-14 | ||
临床2期 | 22 | 齋餘範遞遞鬱構夢簾製(襯艱壓觸鹹製艱膚築範) = 觸構鬱鹹鏇夢鑰構廠衊 鬱鑰顧積願衊壓網鬱鹽 (鑰淵願膚壓襯醖齋襯壓, 築餘繭糧積積醖網膚膚 ~ 鏇鏇簾簾製鏇艱願鹽選) 更多 | - | 2023-07-13 |
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