Cd(Ⅱ)—米诺膦酸配合物的制备与表征实验

介绍了米诺膦酸配体的合成方法及水热法合成Cd(Ⅱ)—米诺膦酸配合物单晶的实验方法与表征手段。该实验涵盖了有机环化反应和Arbuzov反应等多种反应类型,并运用单晶衍射和波谱学技术对化合物进行表征,反映了科研型综合开放实验在教学中的成果,学科覆盖面广,可操作性强,实验效果好,有利于培养学生的综合实践能力和创新能力。     

2-(咪唑并[1,2-a]吡啶-3-基)乙酸的制备

研究了一种用于治疗骨质疏松症药物的关键中间体米诺膦酸的制备方法。实验以二乙氧基膦酰乙酸乙酯和2,2-二甲氧基乙醛为起始原料,经维蒂希-霍纳反应、水解、环合、水解4步制备得到标题化合物。其熔点与1HNMR和文献报道的结果一致,总收率87.5%(以2-氨基吡啶计)。该方法克服了文献报道的工艺缺陷,与现有技术相比,后处理更简单,更适合工业化生产。     

Synthesis of 2-( imidazo [1,2-a] pyridin-3-yl) acetic acid

研究了一种用于治疗骨质疏松症药物的关键中间体米诺膦酸的制备方法.实验以二乙氧基膦酰乙酸乙酯和2,2-二甲氧基乙醛为起始原料,经维蒂希-霍纳反应、水解、环合、水解4步制备得到标题化合物.其熔点与1HNMR和文献报道的结果一致,总收率87.5％(以2-氨基吡啶计).该方法克服了文献报道的工艺缺陷,与现有技术相比,后处理更简单,更适合工业化生产.     

一种抗肿瘤的联合用药物

正本发明公开了一种抗肿瘤的联合用药物。该抗肿瘤的联合用药物包括作为活性成分的双膦酸盐类化合物和CIK细胞,所述的双膦酸盐类化合物为临床用药依替膦酸二钠、氯膦酸二钠、帕米膦酸二钠、替鲁膦酸二钠、阿仑膦酸钠、奈立膦酸钠、奥帕膦酸钠、利塞膦酸钠、伊班膦酸钠、英卡膦酸二钠和唑来膦酸中的至少一种。本发明利用抗肿瘤骨转移的双膦酸盐药物与CIK细胞联合使用,极大提高CIK细     

苯基膦酸及其衍生物

苯基膦酸及其衍生物的商品有:苯基膦酸、苯基膦酰二氯和苯基膦酸二甲酯等三种。 1.毒性口服毒性(对小自鼠LD_(50))为:苯基膦酸3,220毫克/公斤、苯基膦酰二氯3,220毫克/公斤、苯基膦酸二甲酯765毫克/公斤。     

利塞膦酸的合成及市场前景

利塞膦酸是抗骨质疏松药利塞膦酸钠的重要中间体,介绍了利塞膦酸的合成方法和利塞膦酸钠的市场前景.     

三乙膦酸铝润湿性改善研究

正三乙膦酸铝可湿粉是一种杀菌剂,在防治农作物病害领域应用广泛。目前在农业部登记三乙膦酸铝可湿粉的厂家100多个,产品含量有:40%三乙膦酸铝可湿粉、80%三乙膦酸铝可湿粉、90%三乙膦酸铝可溶粉等。主要用于防治农作物霜霉病、纹枯病、稻瘟病、疫病、瘟病等。三乙膦酸铝可湿粉外观为灰白色或者白色粉末,     

草铵膦铵盐及其中间体的合成

[目的]研究不采用剧毒氰化物原料的非Strecker法合成草铵膦铵盐的工艺路线。[方法]以廉价易得的三氯化磷和亚磷酸三乙酯为原料制备氯代亚膦酸二乙酯,经格氏反应得到甲基亚膦酸二乙酯;甲基亚膦酸二乙酯与二溴乙烷在自制催化剂催化下反应得到甲基(2-溴乙基)膦酸乙酯;然后与乙酰氨基丙二酸二乙酯负离子在甲苯中反应,经盐酸酸化,氨水铵化得到草铵膦铵盐。[结果]以三氯化磷计,甲基亚膦酸二乙酯收率为57.6%;以甲基亚膦酸二乙酯计草铵膦铵盐收率为25.8%;制备的草铵膦铵盐各性能指标与文献相符。[结论]以三氯化磷、亚磷酸三乙酯为原料制备氯代亚膦酸二乙酯,经格氏反应得甲基亚膦酸二乙酯是一条原材料成本较低、收率较高、易于工业化的合成路线;甲基亚磷酸二乙酯与二溴乙烷反应制备甲基(2-溴乙基)膦酸乙酯的反应可通过优化催化剂的设计提高过程收率;草铵膦的收率略低于目前以氰化物为原料的Strecker法。     

高级氧化技术降解有机膦酸的研究进展

综述了不同高级氧化技术降解有机膦酸的研究进展,有机膦酸自身基团种类及数目、水中共存离子及有机物对有机膦酸的降解产生显著的影响;其可被自由基攻击降解,亦可通过分子内电子转移过程被去除,和自由基机制比较,分子内电子转移过程受水体基质干扰更小,在实际废水处理中具有更优异的降解有机膦酸的性能。自由基和非自由基机制下有机膦酸的降解具有类似的氧化机制,均通过C—N或C—P键的断裂实现有机膦酸的降解。提出今后研究的重点应该为实际废水中有机膦酸形态特性分析、降解机制的多样性及普适性探究、磷的回收及工程应用。     

唑来膦酸的合成研究

唑来膦酸属于第三代双膦酸药物,是含氮杂环双膦酸和吡啶双膦酸盐的骨吸收抑制剂。由于具有活性强、毒性低等优点,因而具有良好的应用前景。对唑来膦酸工艺进行了改进,通过加入分散剂解决了膦酸化步骤的固化问题。探索出了一种有效的分散剂,解决了双膦酸类化合物制备过程中膦酸化步骤容易固化结块制约工业化生产的问题,经工业放大生产被证明该改进工艺是可行的,合理的。     

Role of the Myokine Irisin on Bone Homeostasis: Review of the Current Evidence

Bone is a highly dynamic tissue that is constantly adapting to micro-changes to facilitate movement. When the balance between bone building and resorption shifts more towards bone resorption, the result is reduced bone density and mineralization, as seen in osteoporosis or osteopenia. Current treatment strategies aimed to improve bone homeostasis and turnover are lacking in efficacy, resulting in the search for new preventative and nutraceutical treatment options. The myokine irisin, since its discovery in 2012, has been shown to play an important role in many tissues including muscle, adipose, and bone. Evidence indicate that irisin is associated with increased bone formation and decreased bone resorption, leading to reduced risk of osteoporosis in post-menopausal women. In addition, low serum irisin levels have been found in individuals with osteoporosis and osteopenia. Irisin targets key signaling proteins, promoting osteoblastogenesis and reducing osteoclastogenesis. The present review summarizes the existing evidence regarding the effects of irisin on bone homeostasis.     

A Comprehensive Mixture of Tobacco Smoke Components Retards Orthodontic Tooth Movement via the Inhibition of Osteoclastogenesis in a Rat Model

Tobacco smoke is a complex mixture of numerous components. Nevertheless, most experiments have examined the effects of individual chemicals in tobacco smoke. The comprehensive effects of components on tooth movement and bone resorption remain unexplored. Here, we have shown that a comprehensive mixture of tobacco smoke components (TSCs) attenuated bone resorption through osteoclastogenesis inhibition, thereby retarding experimental tooth movement in a rat model. An elastic power chain (PC) inserted between the first and second maxillary molars robustly yielded experimental tooth movement within 10 days. TSC administration effectively retarded tooth movement since day 4. Histological evaluation disclosed that tooth movement induced bone resorption at two sites: in the bone marrow and the peripheral bone near the root. TSC administration significantly reduced the number of tartrate-resistant acid phosphatase (TRAP)-positive osteoclastic cells in the bone marrow cavity of the PC-treated dentition. An in vitro study indicated that the inhibitory effects of TSCs on osteoclastogenesis seemed directed more toward preosteoclasts than osteoblasts. These results indicate that the comprehensive mixture of TSCs might be a useful tool for detailed verification of the adverse effects of tobacco smoke, possibly contributing to the development of reliable treatments in various fields associated with bone resorption.     

Myricetin Prevents Alveolar Bone Loss in an Experimental Ovariectomized Mouse Model of Periodontitis

Periodontitis is a common chronic inflammatory disease, which leads to alveolar bone resorption. Healthy and functional alveolar bone, which can support the teeth and enable their movement, is very important for orthodontic treatment. Myricetin inhibited osteoclastogenesis by suppressing the expression of some genes, signaling pathways, and cytokines. This study aimed to investigate the effects of myricetin on alveolar bone loss in an ovariectomized (OVX) mouse model of periodontitis as well as in vitro osteoclast formation and bone resorption. Twenty-four healthy eight-week-old C57BL/J6 female mice were assigned randomly to four groups: phosphate-buffered saline (PBS) control (sham) OVX + ligature + PBS (vehicle), and OVX + ligature + low or high (2 or 5 mg∙kg⁻¹∙day⁻¹, respectively) doses of myricetin. Myricetin or PBS was injected intraperitoneally (i.p.) every other day for 30 days. The maxillae were collected and subjected to further examination, including micro-computed tomography (micro-CT), hematoxylin and eosin (H&E) staining, and tartrate-resistant acid phosphatase (TRAP) staining; a resorption pit assay was also performed in vitro to evaluate the effects of myricetin on receptor activator of nuclear factor κ-B ligand (RANKL)-induced osteoclastogenesis. Myricetin, at both high and low doses, prevented alveolar bone resorption and increased alveolar crest height in the mouse model and inhibited osteoclast formation and bone resorption in vitro. However, myricetin was more effective at high dose than at low dose. Our study demonstrated that myricetin had a positive effect on alveolar bone resorption in an OVX mouse model of periodontitis and, therefore, may be a potential agent for the treatment of periodontitis and osteoporosis.     

Calycosin Suppresses RANKL-Mediated Osteoclastogenesis through Inhibition of MAPKs and NF-κB

Calycosin, an isoflavonoid phytoestrogen, isolated from Radix Astragali, was reported to possess anti-tumor, anti-inflammation, and osteogenic properties, but its impact on osteoclast differentiation remains unclear. In this study, we examined the effects of calycosin on osteoclastogenesis induced by RANKL. The results showed that calycosin significantly inhibited RANKL-induced osteoclast formation from primary bone marrow macrophages (BMMs). Calycosin also dose-dependently suppressed the formation of bone resorption pits by mature osteoclasts. In addition, the expression of osteoclatogenesis-related genes, including cathepsin K (CtsK), tartrate-resistant acid phosphatase (TRAP), and MMP-9, was significantly inhibited by calycosin. Furthermore, the results indicated that calycosin down-regulated the expression levels of NFATc1 and c-Fos through suppressing the activation of NF-κB and MAPKs. Our results indicate that calycosin has an inhibitory role in the bone loss by preventing osteoclast formation, as well as its bone resorptive activity. Therefore, calycosin may be useful as a therapeutic reagent for bone loss-associated diseases.     

Osteoprotective Effects of Loganic Acid on Osteoblastic and Osteoclastic Cells and Osteoporosis-Induced Mice

Osteoporosis is a common disease caused by an imbalance of processes between bone resorption by osteoclasts and bone formation by osteoblasts in postmenopausal women. The roots of Gentiana lutea L. (GL) are reported to have beneficial effects on various human diseases related to liver functions and gastrointestinal motility, as well as on arthritis. Here, we fractionated and isolated bioactive constituent(s) responsible for anti-osteoporotic effects of GL root extract. A single phytochemical compound, loganic acid, was identified as a candidate osteoprotective agent. Its anti-osteoporotic effects were examined in vitro and in vivo. Treatment with loganic acid significantly increased osteoblastic differentiation in preosteoblast MC3T3-E1 cells by promoting alkaline phosphatase activity and increasing mRNA expression levels of bone metabolic markers such as Alpl, Bglap, and Sp7. However, loganic acid inhibited osteoclast differentiation of primary-cultured monocytes derived from mouse bone marrow. For in vivo experiments, the effect of loganic acid on ovariectomized (OVX) mice was examined for 12 weeks. Loganic acid prevented OVX-induced bone mineral density loss and improved bone structural properties in osteoporotic model mice. These results suggest that loganic acid may be a potential therapeutic candidate for treatment of osteoporosis.     

Spherical instrumented indentation as a tool to characterize porous bioceramics and their resorption

Resorbable ceramics used as porous bone substitutes are designed to favor bone in-growth and to be gradually replaced by natural tissues after in vivo resorption. However, a lack of experimental techniques to quantitatively monitor the evolution of their mechanical properties during resorption is noted. In this paper, we propose to use spherical instrumented indentation to follow-up the resorption of microporous resorbable ceramics at a local scale. Tests were performed at the core and at the surface of samples immersed for different durations in model fluids. Instrumented indentation was found to be an efficient technique to characterize and to follow-up the resorption of microporous ceramics, in excellent agreement with microstructural changes observed with X-ray diffraction and X-ray tomography. Instrumented indentation has the ability to capture the presence of gradients in the samples, enables the direct testing of wet samples and appears as a superior technique to compression tests mostly used in the literature.     

Lumican Inhibits Osteoclastogenesis and Bone Resorption by Suppressing Akt Activity

Lumican, a ubiquitously expressed small leucine-rich proteoglycan, has been utilized in diverse biological functions. Recent experiments demonstrated that lumican stimulates preosteoblast viability and differentiation, leading to bone formation. To further understand the role of lumican in bone metabolism, we investigated its effects on osteoclast biology. Lumican inhibited both osteoclast differentiation and in vitro bone resorption in a dose-dependent manner. Consistent with this, lumican markedly decreased the expression of osteoclastogenesis markers. Moreover, the migration and fusion of preosteoclasts and the resorptive activity per osteoclast were significantly reduced in the presence of lumican, indicating that this protein affects most stages of osteoclastogenesis. Among RANKL-dependent pathways, lumican inhibited Akt but not MAP kinases such as JNK, p38, and ERK. Importantly, co-treatment with an Akt activator almost completely reversed the effect of lumican on osteoclast differentiation. Taken together, our findings revealed that lumican inhibits osteoclastogenesis by suppressing Akt activity. Thus, lumican plays an osteoprotective role by simultaneously increasing bone formation and decreasing bone resorption, suggesting that it represents a dual-action therapeutic target for osteoporosis.