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1. 发明授权

US4931287A Heterogeneous interpenetrating polymer networks for the controlled release of drugs 失效
标题翻译：用于控释药物的非均相互穿聚合物网络
公开(公告)号：US4931287A
公开(公告)日：1990-06-05
申请号：US206593
申请日：1988-06-14
申请人： You H. Bae , Teruo Okano , Sung W. Kim
发明人： You H. Bae , Teruo Okano , Sung W. Kim
IPC分类号： A61K9/20
CPC分类号： A61K9/2031 , A61K9/2027
摘要： A heterogeneous interpenetrating polymer network is provided for use in the controlled release of drugs. The network is a heterogeneous matrix that is formed from a hydrophilic component such as polyethylene oxide or poly(N,N'-dimethyl acrylamide-co-styrene) and a hydrophobic component such as styrene, an alkyl methacrylate, or polytetramethylene ether glycol. The relative amounts of the two components, or "domains", can be varied, as can the diffusivities and solubilities of the drug combinations to be loaded therein, to control and change as desired the timed release profile of incorporated drug. Prolonged pseudo-zero order release can be obtained where one domain acts as a diffusion barrier layer to the release of drug from the other domain.
摘要翻译：提供异构互穿聚合物网络用于药物的控制释放。该网络是由亲水组分如聚环氧乙烷或聚（N，N'-二甲基丙烯酰胺 - 共 - 苯乙烯）和疏水组分如苯乙烯，甲基丙烯酸烷基酯或聚四亚甲基醚二醇形成的非均相基体。可以改变两种组分或“结构域”的相对量，以及待加载的药物组合的扩散性和溶解度，以控制并根据需要改变并入药物的定时释放曲线。可以获得延长的伪零次释放，其中一个结构域充当从另一个域释放药物的扩散阻挡层。

2. 发明授权

US5226902A Pulsatile drug delivery device using stimuli sensitive hydrogel 失效
标题翻译：使用刺激敏感水凝胶的脉冲药物递送装置
公开(公告)号：US5226902A
公开(公告)日：1993-07-13
申请号：US737675
申请日：1991-07-30
申请人： You H. Bae , Sung W. Kim , Lev I. Valuev
发明人： You H. Bae , Sung W. Kim , Lev I. Valuev
IPC分类号： A61K9/00 , A61K9/22
CPC分类号： A61K9/0004 , Y10S514/965
摘要： A device for the dispensing of a biologically active material into the surrounding environment is disclosed which consists of at least one wall enclosing a compartment which contains a swollen stimuli sensitive hydrogel in which the biologically active material is entrained in solution. The hydrogel deswells or shrinks in response to contact by external physical or chemical stimuli releasing the biologically active material into the portion of the compartment previously occupied by the swollen hydrogel. The wall enclosing the compartment is rigid and contains means allowing the passage of the biologically active material from the compartment to the surrounding environment and also for transmitting the external stimuli to the swollen hydrogel in said compartment. The wall may contain orifices or be permeable to the active material and external stimuli depending upon the drug and the stimuli to be used. The hydrogel reversibly deswells, shrinks or contracts in response to stimuli, such as temperature, pH, ionic strength, glucose concentration or metabolites in the body and then reswells and reentrains active material not diffused from the compartment when the stimuli is removed. The wall may consist of one or more layers which, in combination, provide for the expeditious delivery of the active substance either through permeation through the wall or through orifices in the wall and also for the conducting of the external stimuli through the wall into the compartment to trigger the deswelling of the hydrogel.
摘要翻译：公开了一种用于将生物活性物质分配到周围环境中的装置，其由至少一个包围腔室的壁组成，所述隔室包含溶胀的刺激性敏感水凝胶，其中生物活性物质被夹带在溶液中。水凝胶响应于外部物理或化学刺激的接触而溶解或收缩，将生物活性物质释放到先前由膨胀的水凝胶占据的隔室部分。包围隔室的壁是刚性的并且包含允许生物活性材料从隔室通过到周围环境的装置，并且还用于将外部刺激传递到所述隔室中的溶胀水凝胶。根据药物和使用的刺激，该壁可能含有孔口或对活性物质可渗透和外部刺激。水凝胶可以响应于身体中的温度，pH，离子强度，葡萄糖浓度或代谢物等刺激而可逆地解冻，收缩或收缩，然后在去除刺激物时，将不会从隔室扩散的活性物质重新流通并重新吸入。该壁可以由一个或多个层组成，其组合地提供活性物质的快速递送，所述活性物质通过壁穿过壁或通过壁中的孔，并且还用于通过壁进入外部刺激进入隔室触发水凝胶的溶解。

3. 发明授权

US5484610A pH and temperature sensitive terpolymers for oral drug delivery 失效
标题翻译： pH和温度敏感的三元共聚物用于口服药物递送
公开(公告)号：US5484610A
公开(公告)日：1996-01-16
申请号：US636747
申请日：1991-01-02
申请人： You H. Bae
发明人： You H. Bae
IPC分类号： A61K9/16 , A61K9/32 , A61K9/14 , A61K9/58 , A61K47/32 , C08F220/06 , C08F220/52
CPC分类号： A61K9/1635 , Y10S526/916
摘要： Terpolymers which are sensitive to pH and temperature are useful carriers for conducting bioactive agents through the gastric juices of the stomach in protected form. Such terpolymers swell at the higher physiologic pH of the intestinal tract causing release of the bioactive agents into the intestine. The terpolymers are linear and are made up of 35 to 99 wt % of a temperature sensitive component, which imparts to the terpolymer LCST (lower critical solution temperature) properties below body temperatures, 1 to 30 wt % of a pH sensitive component having a pK.sub.a in the range of from 2 to 8 which functions through ionization or deionization of carboxylic acid groups to prevent the bioactive agent from being lost at low pH but allows bioactive agent release at physiological pH of about 7.4 and a hydrophobic component which stabilizes the LCST below body temperatures and compensates for bioactive agent effects on the terpolymers. Such terpolymers provide for safe bioactive agent loading, a simple procedure for dosage form fabrication and the terpolymer functions as a protective carrier in the acidic environment of the stomach and also protects the bioactive agents from digestive enzymes until the bioactive agent is released in the intestinal tract.
摘要翻译：对pH和温度敏感的三元共聚物是用于通过受保护形式的胃的胃液导入生物活性剂的有用载体。这种三元共聚物在肠道的较高生理pH下膨胀，导致生物活性剂释放到肠中。三元共聚物是线性的，并且由35至99重量％的温度敏感组分组成，其赋予低于体温的三元共聚物LCST（较低临界溶解温度）性质，1至30重量％的具有pKa的pH敏感组分在2至8的范围内，其通过羧酸基团的离子化或去离子发挥作用，以防止生物活性剂在低pH下丧失，但允许生物活性剂在约7.4的生理pH下释放，以及使LCST在体下稳定的疏水组分温度和补偿生物活性剂对三元共聚物的影响。这种三元共聚物提供安全的生物活性剂负载，用于剂型制备的简单程序，三元共聚物在胃的酸性环境中作为保护性载体起作用，并保护生物活性剂免于消化酶直到生物活性剂在肠道中释放。

4. 发明授权

US5354264A Gas pressure driven infusion system by hydrogel electrolysis 失效
标题翻译：通过水凝胶电解气压驱动输液系统
公开(公告)号：US5354264A
公开(公告)日：1994-10-11
申请号：US18937
申请日：1993-02-17
申请人： You H. Bae , Ick C. Kwon
发明人： You H. Bae , Ick C. Kwon
IPC分类号： A61M5/142 , A61M5/155 , A61M1/30
CPC分类号： A61M5/155 , A61M2005/14204
摘要： A drug delivery device is described which utilizes gas pressure from free oxygen and hydrogen derived from the electrolysis of water at the electrodes in negatively charged polymeric hydrogels by electro-osmosis. The gas pressure forces the infusion of the drugs through appropriate means into the body. The rate of electrolysis which produces the oxygen and hydrogen is controlled by an electric current. Therefore the rate of drug delivery can be predetermined and precisely controlled. The current is activated and controlled by an electronic timer or a biomedical control system. The negatively charged hydrogel polymers have mechanical strength and rigidity and allow water to flow through the polymer network toward the cathode ensuring a continuous water supply to the electrodes inside the hydrogel system by electro-osmosis. The hydrogels may be recharged (reswollen) with water or simply replaced. Because the containment of water within the hydrogel structure is not position dependent, gravity plays no part in the gel location within the gas generation unit as in prior art units. Therefore, the contact between the electrodes and water for purposes of electrolysis is position independent.
摘要翻译：描述了一种药物输送装置，其利用来自游离氧气的压力和源于电极中的水的电压，通过电渗透在带负电荷的聚合物水凝胶中。气体压力迫使药物通过适当的方式输入身体。产生氧和氢的电解速率由电流控制。因此，可以预先确定和精确地控制药物递送的速度。电流被电子定时器或生物医学控制系统激活和控制。带负电荷的水凝胶聚合物具有机械强度和刚性，并且允许水通过聚合物网络流向阴极，从而确保通过电渗水连续供水到水凝胶体系内的电极。水凝胶可以用水再次充电（再溶胀）或简单地更换。因为水凝胶结构内的水的容纳不依赖于位置，所以在现有技术单元中，重力在气体发生单元内的凝胶位置中不起作用。因此，为了电解目的，电极和水之间的接触是位置无关的。

5. 发明授权

US5262055A Implantable and refillable biohybrid artificial pancreas 失效
标题翻译：植入式和可再填充生物混合人造胰腺
公开(公告)号：US5262055A
公开(公告)日：1993-11-16
申请号：US962879
申请日：1992-10-19
申请人： You H. Bae , Sun W. Kim
发明人： You H. Bae , Sun W. Kim
IPC分类号： A61F2/02 , B01D61/00 , B01D63/08 , B01D69/06
CPC分类号： A61F2/022
摘要： An artificial pancreas system which minimizes the volume of the artificial pancreas by not encapsulating each islet is taught wherein the islets are separated and held within a polymeric matrix which is soluble in an aqueous solution below body temperature but insoluble in aqueous solutions at or above body temperature. The polymer-islet mixture is contained in a pouch having access means such as entry and exit ports. The solubility makes it possible to replace the contents of the pouch by solubilizing the matrix simply by lowering the temperature below the LCST. The pouch is constructed of a biocompatible material permeable to insulin and other substances of similar or lesser molecular weight but is impermeable to cellular and humoral components of the body immune system. The islet-polymer matrix can be functionalized to stimulate insulin secretion from the islets using insulinotropic agents such as sulfonylurea. Also, polymeric microparticles which release bioactive agents which either promote vascularization at the pouch membrane outer surface or inhibit macrophage activity can be added to the polymer matrix.
摘要翻译：教导了一种通过不封装每个胰岛来最小化人造胰腺体积的人造胰腺系统，其中胰岛被分离并保持在可溶于低于体温的水溶液但不溶于体温或体温以上的水溶液中的聚合物基质中。聚合物 - 胰岛混合物包含在具有入口和出口端口的进入装置的袋中。溶解度使得可以通过简单地通过降低LCST以下的温度来溶解基质来替代袋的内容物。该小袋由可渗透胰岛素的生物相容性材料构成，并且具有相似或较小分子量的其它物质，但对体内免疫系统的细胞和体液组分是不可渗透的。胰岛聚合物基质可以被功能化以利用胰岛素剂如磺酰脲刺激胰岛素的胰岛素分泌。此外，可以向聚合物基质中加入释放促进囊膜外表面的血管形成或抑制巨噬细胞活性的生物活性剂的聚合物微粒。

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