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    • 3. 发明授权
    • Synthetic resin matrix system for the extended delivery of drugs
    • 合成树脂基体系用于延长药物递送
    • US4747845A
    • 1988-05-31
    • US815874
    • 1986-01-03
    • Bernard Korol
    • Bernard Korol
    • A61K9/22A61L15/24A61L15/44A61L26/00C08K5/41A61L15/01A61L15/03A61L15/06C08K5/10C08K5/15C08K5/34
    • A61L26/008A61L15/24A61L15/44A61L26/0014A61L2300/40A61L2300/414A61L2300/602Y10S514/936Y10S514/946Y10S514/965
    • A synthetic resin matrix system for the delayed and extended duration delivery of drugs to humans and animals is disclosed consisting of a polymer, such as poly(2-hydroxyethylmethacrylate), referred to as PHEMA, an organic solvent, such as polyethylene glycol (PEG), and a hydrogen binding plasticizer, such as dimethylsulfoxide (DMSO). The plasticizer regulates the set-up time of the synthetic resin so that the more plasticizer present, the shorter the set-up time. The plasticizer also has a direct shortening effect upon the cure time and also profoundly influences many of the physical characteristics of the resultant synthetic resin matrix system. A variety of drugs can be embodied in the fabricated matrix system and administered to the patient (or animal) by different modes of application, including but not limited to oral, topical, rectal, subcutaneous implant, or organ-specific implant such as in the conjunctival sac of the eye. These formulations and procedures can also be utilized in the storage and extended-duration delivery of agricultural products, particularly herbicides, insecticides, and nutritional supplements. By manipulating the relative concentrations of the components of the matrix system and the particle size of the embedded active agent, it is possible to control the release dynamics of the active embodied agent from the matrix and thus provide unique controlled delayed and extended delivery of the active agent.
    • 公开了一种合成树脂基质体系,其用于将药物延迟和延长的持续递送给人和动物,由聚合物如聚(2-羟乙基甲基丙烯酸酯)(称为PHEMA),有机溶剂如聚乙二醇(PEG) ,以及氢结合增塑剂,例如二甲基亚砜(DMSO)。 增塑剂调节合成树脂的安装时间,使得存在的增塑剂越多,安装时间越短。 增塑剂在固化时间上也具有直接的起酥油作用,并且还对所得合成树脂基质体系的许多物理特性产生深刻的影响。 各种药物可以体现在制造的基质体系中,并通过不同的施用方式施用于患者(或动物),包括但不限于口服,局部,直肠,皮下植入或器官特异性植入物,例如在 眼结膜囊 这些制剂和程序也可用于农产品,特别是除草剂,杀虫剂和营养补充剂的储存和延长持续时间的输送。 通过操纵矩阵系统的组分的相对浓度和嵌入的活性剂的粒度,可以从基质中控制活性实施剂的释放动力学,从而提供活性物质的独特的受控延迟和延长递送 代理商
    • 4. 发明授权
    • Polymer matrices for storage and sustained release of drugs and chemicals
    • 用于储存和持续释放药物和化学品的聚合物基质
    • US06312713B1
    • 2001-11-06
    • US09096739
    • 1998-06-12
    • Bernard KorolPaul Nathan
    • Bernard KorolPaul Nathan
    • A61F1300
    • A61K9/4866A61K9/2013A61K9/2027A61K9/4858A61L15/44A61L2300/602
    • Improved polymeric devices are disclosed which slowly and gradually release drugs or other chemicals, for use as wound dressings that gradually release antibiotics, analgesics, or other useful drugs directly onto the surfaces of wounds. These polymers also provide other sustained-release devices, such as capsules that will gradually release a drug the entire time they remain in the digestive system, until the inert polymer is excreted in feces. These devices are created by reacting: (1) a hydrophilic polymer such as poly(2-hydroxy-ethyl-methacrylate); (2) a solvent such as polyethylene glycol; (3) a plasticizing agent that promotes hydrogen bonding, such as dimethylsulfoxide in a quantity which is substantially reduced compared to prior formulations; and (4) the drug or chemical that is to be slowly released by the final device. The quantity of DMSO has been reduced from about 5%, in previously-known polymer systems, to about 0.1% in these improved devices. This reduction in DMSO content, combined with certain other improvements, doubles the shelf life from 1 year to 2 years, while also eliminating the need to refrigerate these devices until use. The improved polymers also have reduced odors, and reduced discoloration during storage. The new methods and recipes also allow the use of “curing ovens” to accelerate the curing of a liquid slurry into a solidified device. This allows faster, simpler, and more reliable and consistent manufacturing of commercial-scale quantities of these devices.
    • 公开了改进的聚合物装置,其缓慢且逐渐释放药物或其它化学品,用作将伤口敷料直接释放到伤口表面上的伤口敷料。 这些聚合物还提供其它持续释放装置,例如胶囊,其将在药物保留在消化系统中的所有时间内逐渐释放药物,直到惰性聚合物排泄在粪便中。 这些装置是通过使(1)亲水性聚合物如聚(2-羟乙基 - 甲基丙烯酸酯)反应而形成的; (2)溶剂如聚乙二醇; (3)促进氢键的增塑剂,例如二甲基亚砜的量与现有制剂相比大大降低; 和(4)最终装置缓慢释放的药物或化学物质。 在这些改进的装置中,DMSO的量已经从先前已知的聚合物体系中的约5%降低到约0.1%。 DMSO的含量降低,加上某些其他改进,保质期从1年增加到2年,同时也不需要在使用前冷藏这些装置。 改进的聚合物还具有降低的气味,并且在储存期间降低变色。 新的方法和配方还允许使用“固化炉”来加速液体浆料固化成固化装置。 这允许更快,更简单,更可靠和一致地制造商业规模的这些设备。
    • 5. 发明授权
    • Synthetic resin matrix system incorporating healing enhancer
    • 合成树脂基体系结合愈合增强剂
    • US4857334A
    • 1989-08-15
    • US199375
    • 1988-05-27
    • Bernard KorolPaul Nathan
    • Bernard KorolPaul Nathan
    • A61K9/22A61L15/24A61L15/44A61L26/00
    • A61L26/008A61L15/24A61L15/44A61L26/0014A61L2300/40A61L2300/414A61L2300/602Y10S514/936Y10S514/946Y10S514/965
    • An apparatus and method is described for applying epidermal growth factor (EGF) for achieving healing enhancement at a wound site. The human source of epidermal growth factor, designated as hEGF, is applied from the synthetic resin matrix system of this invention, and which comprises a polymer, such as poly(2-hydroxyl ethyl methyl methacrylate), referred to as PHEMA, an organic solvent, such as polyethylene glycol (PEG), and a hydrogen binding plasticizer, such as dimethylsulfoxide (DMSO). The plasticizer regulates the set-up time of the synthetic resin, so that the more plasticizer present, the shorter the set-up time. The dressing, once formed, and having the healing enhancer contained therein, may be sealed within various backing sheets, in order to preserve its aseptic condition. When ready for use, one of the backing sheets may be peeled away to expose the resin pad with the emobodied healing enhancer, ready for application to the wound site.
    • 描述了一种用于在伤口部位应用表皮生长因子(EGF)用于实现愈合增强的装置和方法。 称为hEGF的人表皮生长因子来源于本发明的合成树脂基质体系,其包含聚合物,例如聚(2-羟乙基甲基丙烯酸甲酯),称为PHEMA,有机溶剂 ,例如聚乙二醇(PEG)和氢结合增塑剂如二甲基亚砜(DMSO)。 增塑剂调节合成树脂的安装时间,使得存在的增塑剂越多,安装时间越短。 一旦形成并且其中含有愈合增强剂的敷料可以被密封在各种背衬片内,以便保持其无菌状态。 当准备使用时,其中一个背衬片可能被剥离,以暴露树脂垫与表面的愈合增强剂,准备应用于伤口部位。
    • 6. 发明授权
    • Anti-microbial sensitivity test and testing stratum
    • 抗菌敏感性试验和试验层
    • US4820292A
    • 1989-04-11
    • US199379
    • 1988-05-27
    • Bernard KorolPaul Nathan
    • Bernard KorolPaul Nathan
    • A61L15/24A61L15/44A61L26/00C08K5/41C08K5/10C08K5/15C08K5/34
    • A61L26/008A61L15/24A61L15/44A61L26/0014A61L2300/102A61L2300/104A61L2300/204A61L2300/404
    • An anti-microbial sensitivity test and testing stratum is disclosed for evaluating the sensitivity of different anti-microbial agents relative to identifiable microbial contaminants. The test stratum comprises a polymer such as poly(2-hydroxyethylmethacrylate) referred to as PHEMA, an organic solvent, such as polyethylene glycol (PEG), a hydrogen binding plasticizer, such as dimethylsulfoxide (DMSO), an an anti-microbial agent such as silver sulfadiazine, mafenide, nystatin, nitrofurazone, silver nitrate, bacitracin, gentamicin, amphotericin B, cesium nitrate, or other anti-microbial agents. The test includes positioning testing stratum of the type described, each having a different anti-microbial agent therein, on a sterile plate or on an agar substrate and spaced in fixed relationship to one another. The testing stratum are self adhering and remain fixed on a sterile plate, or on an applicator, even when the sterile plate, is inverted. The testing stratum further provide a sustained release of the anti-microbial agent incorporated therein. The testing stratum are then subjected to samples from the wound site, often containing microbial contaminants, and after a predetermined period of incubation, evaluation indicative of microbial contamination can then be made and examination of the zones of inhibition over and around each of the anti-microbial testing stratum will determine effectiveness of each anti-microbial agent contained in the test system.
    • 公开了抗微生物敏感性测试和测试层,用于评估不同抗微生物剂相对于可识别的微生物污染物的敏感性。 测试层包括聚合物,例如称为PHEMA的聚(2-羟乙基甲基丙烯酸酯),有机溶剂如聚乙二醇(PEG),氢结合增塑剂如二甲基亚砜(DMSO),抗微生物剂如 作为磺胺嘧啶银,马法尼酸,制霉菌素,硝基呋喃西林,硝酸银,杆菌肽,庆大霉素,两性霉素B,硝酸铯或其他抗微生物剂。 该测试包括所述类型的定位测试层,每层具有不同的抗微生物剂,在无菌板或琼脂基底上,彼此间隔固定。 测试层是自粘的,并保持固定在无菌板上或涂抹器上,即使无菌板倒置。 测试层进一步提供其中并入的抗微生物剂的持续释放。 然后将测试层从伤口部位进行样品,通常含有微生物污染物,并且在预定的温育期之后,然后可以进行指示微生物污染的评估,并检查每个抗 - 微生物测试层将确定测试系统中所含的每种抗微生物剂的有效性。