公开(公告)号：US10588860B2

公开(公告)日：2020-03-17

申请号：US15228686

申请日：2016-08-04

Applicant: Edward Turos ,  Raphael Labruere ,  Ryan Scott Cormier ,  Renaud Sicard

Inventor： Edward Turos ,  Raphael Labruere ,  Ryan Scott Cormier ,  Renaud Sicard

IPC: A61K9/14 ,  A61K9/00 ,  A61K9/10 ,  A61K9/51 ,  A61K47/10 ,  A61K49/00 ,  A61K47/69

Abstract: The present invention comprises poly(vinyl benzoate) nanoparticle suspensions as molecular carriers. These nanoparticles can be formed by nanoprecipitation of poly(vinyl benzoate) in water using Pluronic F68 as surfactant, to create spherical nanostructures measuring about 200-250 nm in diameter which are stable in phosphate buffer and blood serum, and only slowly degrade in the presence of esterases. Kinetics experiments in phosphate buffer indicate that 78% of the coumarin-6 was encapsulated within the polymer matrix of the nanoparticle, and the residual 22% of coumarin-6 was surface-bound and quickly released. The nanoparticles are non-toxic in vitro towards human epithelial cells (IC50>1000 μg/mL) and primary bovine primary aortic endothelial cells (IC50>500 μg/mL), and exert non-observable bactericidal activity against a selection of representative test microbes (MIC>250 μg/mL). Poly(vinyl benzoate) nanoparticles are suitable carriers for molecular delivery of lipophilic small molecules such as drugs pharmaceutical and imaging agents.

公开(公告)号：US09433581B2

公开(公告)日：2016-09-06

申请号：US13897868

申请日：2013-05-20

Applicant: Edward Turos ,  Raphael Labruere ,  Ryan Scott Cormier ,  Renaud Sicard

Inventor： Edward Turos ,  Raphael Labruere ,  Ryan Scott Cormier ,  Renaud Sicard

IPC: A61K9/14 ,  A61K9/00 ,  A61K9/10 ,  A61K9/51 ,  A61K47/10 ,  A61K47/48 ,  A61K49/00

CPC classification number: A61K9/146 ,  A61K9/0019 ,  A61K9/10 ,  A61K9/5138 ,  A61K47/10 ,  A61K47/489 ,  A61K47/6933 ,  A61K49/0039 ,  A61K49/0043 ,  A61K49/0093

Abstract: The present invention comprises poly(vinyl benzoate) nanoparticle suspensions as molecular carriers. These nanoparticles can be formed by nanoprecipitation of poly(vinyl benzoate) in water using Pluronic F68 as surfactant, to create spherical nanostructures measuring about 200-250 nm in diameter which are stable in phosphate buffer and blood serum, and only slowly degrade in the presence of esterases. Kinetics experiments in phosphate buffer indicate that 78% of the coumarin-6 was encapsulated within the polymer matrix of the nanoparticle, and the residual 22% of coumarin-6 was surface-bound and quickly released. The nanoparticles are non-toxic in vitro towards human epithelial cells (IC50>1000 μg/mL) and primary bovine primary aortic endothelial cells (IC50>500 μg/mL), and exert non-observable bactericidal activity against a selection of representative test microbes (MIC>250 μg/mL). Poly(vinyl benzoate) nanoparticles are suitable carriers for molecular delivery of lipophilic small molecules such as drugs pharmaceutical and imaging agents.

Abstract translation: 本发明包括作为分子载体的聚（苯甲酸乙烯酯）纳米颗粒悬浮液。 这些纳米颗粒可以通过使用Pluronic F68作为表面活性剂在水中的聚（乙烯基苯甲酸酯）的纳米沉淀形成，以产生直径约200-250nm的球形纳米结构，其在磷酸盐缓冲液和血清中是稳定的，并且在存在下仅缓慢降解 的酯酶。 在磷酸盐缓冲液中的动力学实验表明，78％的香豆素-6被包封在纳米颗粒的聚合物基质内，剩余的22％的香豆素-6被表面结合并迅速释放。 纳米颗粒在体外对人上皮细胞（IC50>1000μg/ mL）和原代牛主动脉内皮细胞（IC50>500μg/ mL）无毒性，并且对代表性测试微生物的选择施加不可观察的杀菌活性 （MIC>250μg/ mL）。 聚（苯甲酸乙烯酯）纳米颗粒是分子递送亲脂性小分子如药物药物和成像剂的合适的载体。

公开(公告)号：US08143398B1

公开(公告)日：2012-03-27

申请号：US13031991

申请日：2011-02-22

Applicant: Edward Turos ,  Burt E. Anderson ,  Ryan Scott Cormier ,  John C. Thomas ,  Rebecca J. Kapolka ,  Glenn Roma

Inventor： Edward Turos ,  Burt E. Anderson ,  Ryan Scott Cormier ,  John C. Thomas ,  Rebecca J. Kapolka ,  Glenn Roma

IPC: C07D241/04

CPC classification number: C07D241/04

Abstract: Bartonella species are facultative intracellular pathogens responsible for a range of diseases in animals and in humans. A selection of N-acyl ciprofloxacin analogues, chemically synthesized from ciprofloxacin, have been tested in vitro for activity against Bartonella species as models for therapeutic development. Nine Bartonella strains, including five of B. henselae, two of B. quintana, and one each of B. elizabethae and B. vinsonii, have been tested for susceptibility to different N-acyl ciprofloxacin derivatives. Several techniques have been used to test the in vitro antibacterial activity of the derivatives. Seven of them, labeled RC4-125, RC4-143, RC4-147, RC5-28, RC5-29, RC5-32 and RC5-69 showed significant intracellular anti-Bartonella activity. These synthetically derived N-acyl ciprofloxacin derivatives may be useful in the therapeutic treatment of infections caused by Bartonella.

Abstract translation: 巴尔多奈属物种是造成动物和人类各种疾病的兼性细胞内病原体。 已经在体外测试了从环丙沙星化学合成的N-酰基环丙沙星类似物的选择，用于针对巴氏杆菌属物种的活性作为治疗发展的模型。 已经测试了九种巴尔通体菌株，其中包括五种B.henselae，两种金针菇，以及一种每种B. elizabethae和B.vinsonii，已经测试了对不同N-酰基环丙沙星衍生物的易感性。 已经使用几种技术来测试衍生物的体外抗菌活性。 其中7个标记为RC4-125，RC4-143，RC4-147，RC5-28，RC5-29，RC5-32和RC5-69，显示出显着的细胞内抗Bartonella活性。 这些合成衍生的N-酰基环丙沙星衍生物可用于治疗由巴氏杆菌引起的感染的治疗。

公开(公告)号：US20160338962A1

公开(公告)日：2016-11-24

申请号：US15228686

申请日：2016-08-04

Applicant: Edward Turos ,  Raphael Labruere ,  Ryan Scott Cormier ,  Renaud Sicard

Inventor： Edward Turos ,  Raphael Labruere ,  Ryan Scott Cormier ,  Renaud Sicard

IPC: A61K9/14

CPC classification number: A61K9/146 ,  A61K9/0019 ,  A61K9/10 ,  A61K9/5138 ,  A61K47/10 ,  A61K47/6933 ,  A61K49/0039 ,  A61K49/0043 ,  A61K49/0093

Abstract: The present invention comprises poly(vinyl benzoate) nanoparticle suspensions as molecular carriers. These nanoparticles can be formed by nanoprecipitation of poly(vinyl benzoate) in water using Pluronic F68 as surfactant, to create spherical nanostructures measuring about 200-250 nm in diameter which are stable in phosphate buffer and blood serum, and only slowly degrade in the presence of esterases. Kinetics experiments in phosphate buffer indicate that 78% of the coumarin-6 was encapsulated within the polymer matrix of the nanoparticle, and the residual 22% of coumarin-6 was surface-bound and quickly released. The nanoparticles are non-toxic in vitro towards human epithelial cells (IC50>1000 μg/mL) and primary bovine primary aortic endothelial cells (IC50>500 μg/mL), and exert non-observable bactericidal activity against a selection of representative test microbes (MIC>250 μg/mL). Poly(vinyl benzoate) nanoparticles are suitable carriers for molecular delivery of lipophilic small molecules such as drugs pharmaceutical and imaging agents.

Abstract translation: 本发明包括作为分子载体的聚（苯甲酸乙烯酯）纳米颗粒悬浮液。 这些纳米颗粒可以通过使用Pluronic F68作为表面活性剂在水中的聚（乙烯基苯甲酸酯）的纳米沉淀形成，以产生直径约200-250nm的球形纳米结构，其在磷酸盐缓冲液和血清中是稳定的，并且在存在下仅缓慢降解 的酯酶。 在磷酸盐缓冲液中的动力学实验表明，78％的香豆素-6被包封在纳米颗粒的聚合物基质内，剩余的22％的香豆素-6被表面结合并迅速释放。 纳米颗粒在体外对人上皮细胞（IC50>1000μg/ mL）和原代牛主动脉内皮细胞（IC50>500μg/ mL）无毒性，并且对代表性测试微生物的选择施加不可观察的杀菌活性 （MIC>250μg/ mL）。 聚（苯甲酸乙烯酯）纳米颗粒是分子递送亲脂性小分子如药物药物和成像剂的合适的载体。

公开(公告)号：US20130243832A1

公开(公告)日：2013-09-19

申请号：US13897868

申请日：2013-05-20

Applicant: Edward Turos ,  Raphael Labruere ,  Ryan Scott Cormier ,  Renaud Sicard

Inventor： Edward Turos ,  Raphael Labruere ,  Ryan Scott Cormier ,  Renaud Sicard

IPC: A61K9/14

CPC classification number: A61K9/146 ,  A61K9/0019 ,  A61K9/10 ,  A61K9/5138 ,  A61K47/10 ,  A61K47/489 ,  A61K47/6933 ,  A61K49/0039 ,  A61K49/0043 ,  A61K49/0093

Abstract: The present invention comprises poly(vinyl benzoate) nanoparticle suspensions as molecular carriers. These nanoparticles can be formed by nanoprecipitation of poly(vinyl benzoate) in water using Pluronic F68 as surfactant, to create spherical nanostructures measuring about 200-250 nm in diameter which are stable in phosphate buffer and blood serum, and only slowly degrade in the presence of esterases. Kinetics experiments in phosphate buffer indicate that 78% of the coumarin-6 was encapsulated within the polymer matrix of the nanoparticle, and the residual 22% of coumarin-6 was surface-bound and quickly released. The nanoparticles are non-toxic in vitro towards human epithelial cells (IC50>1000 μg/mL) and primary bovine primary aortic endothelial cells (IC50>500 μg/mL), and exert non-observable bactericidal activity against a selection of representative test microbes (MIC >250 μg/mL). Poly(vinyl benzoate) nanoparticles are suitable carriers for molecular delivery of lipophilic small molecules such as drugs pharmaceutical and imaging agents.

Abstract translation: 本发明包括作为分子载体的聚（苯甲酸乙烯酯）纳米颗粒悬浮液。 这些纳米颗粒可以通过使用Pluronic F68作为表面活性剂在水中的聚（乙烯基苯甲酸酯）的纳米沉淀形成，以产生直径约200-250nm的球形纳米结构，其在磷酸盐缓冲液和血清中是稳定的，并且在存在下仅缓慢降解 的酯酶。 在磷酸盐缓冲液中的动力学实验表明，78％的香豆素-6被包封在纳米颗粒的聚合物基质内，剩余的22％的香豆素-6被表面结合并迅速释放。 纳米颗粒在体外对人上皮细胞无毒性（IC50> 1000mug / mL）和原代牛原发性主动脉内皮细胞（IC50> 500mug / mL），并对选择的代表性测试微生物施加不可观察的杀菌活性 （MIC> 250mug / mL）。 聚（苯甲酸乙烯酯）纳米颗粒是分子递送亲脂性小分子如药物药物和成像剂的合适的载体。