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1.发明授权Method for preventing the formation of a crystalline hydrate in a dispersion of a liquid in a monaqueous matrix 失效用于防止在单水基质中的液体分散体中形成结晶水合物的方法
公开(公告)号：US4832953A
公开(公告)日：1989-05-23
申请号：US85052
申请日：1987-08-13
IPC分类号： A61K9/70
CPC分类号： A61K9/7053 , A61K9/7084
摘要： A method for preventing the formation of crystalline hydrates in a dispersion of a hydratable liquid in a nonaqueous matrix is disclosed. The method is particularly useful in the manufacture of laminated items formed from such dispersions and comprises forming individual subunits from such dispersions, heating the subunits, preferably after they have been packed in sealed containers, to a temperature high enough to melt the crystalline hydrate, maintaining said subunits at such temperature for a time sufficient to melt all the crystalline hydrate present and to prevent the occurrence of crystals for an extended period of time after cooling and cooling subunits to ambient conditions. The use of the method in the manufacture of transdermal delivery devices for the delivery of scopolamine base is described.
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2.发明授权Subsaturated transdermal therapeutic system having improved release characteristics 失效具有改善的释放特性的亚饱和透皮治疗系统
公开(公告)号：US5342623A
公开(公告)日：1994-08-30
申请号：US80645
申请日：1993-06-18
CPC分类号： A61K9/7084 , A61K31/46
摘要： Rate controlled transdermal delivery devices are disclosed which utilize an in-line adhesive to maintain the device on the skin and deliver an agent which is a solvent or a plasticizer for the in-line adhesive. The initial equilibrated concentration of the agent in the agent reservoir and the adhesive is below saturation, and the reservoir comprises the agent dissolved in a solvent with respect to which the rate controlling element of the device is substantially impermeable. In preferred embodiments the initial loading of the agent in reservoir is sufficient to prevent the activity of the agent in the reservoir from decreasing by more than about 50% and preferably no more than about 25% during the predetermined period of administration; and the thicknesses of the adhesive, rate controlling membrane and reservoir layers are selected so that at least 50% and preferably at least 75% initial equilibrated agent loading is in the reservoir layer. The devices are usable to deliver agents which are liquid at body temperatures such as benztropine, secoverine, nicotine, arecoline, polyethylene glycol monolaurate, glycerol monolaurate, glycerol monooleate and ethanol, for example.
摘要翻译： 公开了速率控制的透皮递送装置，其使用直列粘合剂将装置保持在皮肤上并输送作为在线粘合剂的溶剂或增塑剂的试剂。 试剂储存器和粘合剂中试剂的初始平衡浓度低于饱和，并且储存器包含溶解在溶剂中的试剂，其中装置的速率控制元件基本上不可渗透。 在优选的实施方案中，试剂在储存器中的初始加载量足以防止储存器中的试剂的活性在给定的给药期间减少超过约50％，优选不超过约25％ 并且选择粘合剂，速率控制膜和储层的厚度，使得至少50％，优选至少75％的初始平衡剂负载在储层中。 这些装置可用于例如递送在体温下为液体的药剂，例如苯托品，脱毛，尼古丁，槟榔碱，聚乙二醇单月桂酸酯，甘油单月桂酸酯，甘油单油酸酯和乙醇。
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3.发明授权Subsaturated transdermal therapeutic system having improved release characteristics 失效具有改善的释放特性的亚饱和透皮治疗系统
公开(公告)号：US4908027A
公开(公告)日：1990-03-13
申请号：US906730
申请日：1986-09-12
CPC分类号： A61K9/7084 , A61K31/46
摘要： Rate-controlled transdermal delivery devices are disclosed which utilize an in-line adhesive to maintain the device on the skin and deliver an agent which is a solvent for the in-line adhesive. The initial equilibrated concentration of the agent in the agent reservoir and the adhesive is below saturation and the reservoir comprises the agent dissolved in a solvent with respect to which the rate controlling element of the device is substantially impermeable. In preferred embodiments the initial loading of the agent in reservoir is sufficient to prevent the activity of the agent in the reservoir from decreasing by more than about 50% and preferrably no more than about 25% during the predetermined period of administration; and the thicknesses of the adhesive, rate controlling membrane and reservoir layers are selected so that at least 50% and, preferrably at least 75% initial equilibrated agent loading is in the reservoir layer. The devices are usable to delivery oily non-polar agents which are liquid at body temperatures such as benztropine and secoverine.
摘要翻译： 公开了速率控制的透皮递送装置，其使用直列粘合剂将装置保持在皮肤上并输送作为在线粘合剂的溶剂的试剂。 试剂储存器和粘合剂中的试剂的初始平衡浓度低于饱和，并且储存器包含溶解在溶剂中的试剂，相对于其中装置的速率控制元件基本上不可渗透。 在优选的实施方案中，试剂在储存器中的初始加载足以防止储存器中的试剂的活性在给定的给药期间减少超过约50％，优选不超过约25％; 并且选择粘合剂，速率控制膜和储存器层的厚度，使得至少50％，优选地至少75％的初始平衡剂加载在储层中。 该装置可用于输送在体温下为液体的油性非极性试剂，例如苯托品和脱毛。
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公开(公告)号：US6007837A
公开(公告)日：1999-12-28
申请号：US243890
申请日：1999-02-03
IPC分类号： A61K9/70
CPC分类号： A61K9/7084
摘要： An improved process for manufacturing transdermal drug delivery devices and devices made therefrom. The invention provides a heat equilibration process for the manufacture of drug delivery devices which eliminates the need to preload the body contacting layer with a drug. The method has particular application in the manufacture of transdermal drug delivery devices including a drug reservoir comprising drug in excess of saturation.
摘要翻译： 用于制造透皮药物递送装置和由其制成的装置的改进方法。 本发明提供了用于制造药物递送装置的热平衡过程，其不需要用药物预加载身体接触层。 该方法在制造透皮药物递送装置中具有特别的应用，其包括含有超过饱和的药物的药物储库。
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5.发明授权Subsaturated transdermal therapeutic system having improved release characteristics 失效具有改善的释放特性的亚饱和透皮治疗系统
公开(公告)号：US5462745A
公开(公告)日：1995-10-31
申请号：US297739
申请日：1994-08-30
CPC分类号： A61K9/7084 , A61K31/46
摘要： Rate controlled transdermal delivery devices are disclosed which utilize an in-line adhesive to maintain the device on the skin and deliver an agent which is a solvent or a plasticizer for the in-line adhesive. The initial equilibrated concentration of the agent in the agent reservoir and the adhesive is below saturation, and the reservoir comprises the agent dissolved in a solvent with respect to which the rate controlling element of the device is substantially impermeable. In preferred embodiments the initial loading of the agent in reservoir is sufficient to prevent the activity of the agent in the reservoir from decreasing by more than about 50% and preferably no more than about 25% during the predetermined period of administration: and the thicknesses of the adhesive, rate controlling membrane and reservoir layers are selected so that at least 50% and preferably at least 75% initial equilibrated agent loading is in the reservoir layer. The devices are usable to deliver agents which are liquid at body temperatures such as benztropine, secoverine, nicotine, arecoline, polyethylene glycol monolaurate, glycerol monolaurate, glycerol monooleate and ethanol, for example.
摘要翻译： 公开了速率控制的透皮递送装置，其使用直列粘合剂将装置保持在皮肤上并输送作为在线粘合剂的溶剂或增塑剂的试剂。 试剂储存器和粘合剂中试剂的初始平衡浓度低于饱和，并且储存器包含溶解在溶剂中的试剂，其中装置的速率控制元件基本上不可渗透。 在优选实施方案中，试剂在储存器中的初始加载量足以防止储存器中的试剂在给定施用期间的活性降低超过约50％，优选不超过约25％ 选择粘合剂，速率控制膜和储存层，使得至少50％，优选至少75％的初始平衡剂负载在储层中。 这些装置可用于例如递送在体温下为液体的药剂，例如苯托品，脱毛，尼古丁，槟榔碱，聚乙二醇单月桂酸酯，甘油单月桂酸酯，甘油单油酸酯和乙醇。
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公开(公告)号：US5344656A
公开(公告)日：1994-09-06
申请号：US78540
申请日：1993-06-16
CPC分类号： A61K9/7084 , A61K31/46
摘要： Rate controlled transdermal delivery devices are disclosed which utilize an in-line adhesive to maintain the device on the skin and deliver an agent which is a solvent or a plasticizer for the in-line adhesive. The initial equilibrated concentration of the agent in the agent reservoir and the adhesive is below saturation, and the reservoir comprises the agent dissolved in a solvent with respect to which the rate controlling element of the device is substantially impermeable. In preferred embodiments the initial loading of the agent in reservoir is sufficient to prevent the activity of the agent in the reservoir from decreasing by more than about 50% and preferably no more than about 25% during the predetermined period of administration; and the thicknesses of the adhesive, rate controlling membrane and reservoir layers are selected so that at least 50% and preferably at least 75% initial equilibrated agent loading is in the reservoir layer. The devices are usable to deliver agents which are liquid at body temperatures such as benztropine, secoverine, nicotine, arecoline, polyethylene glycol monolaurate, glycerol monolaurate, glycerol monooleate and ethanol, for example.
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公开(公告)号：US06174545B1
公开(公告)日：2001-01-16
申请号：US09243873
申请日：1999-02-03
IPC分类号： A61F1302
CPC分类号： A61K9/7084 , Y10S514/947
摘要： An improved process for manufacturing transdermal drug delivery devices and devices made therefrom. The invention provides a heat equilibration process for the manufacture of drug delivery devices which eliminates the need to preload the body contacting layer with a drug. The method has particular application in the manufacture of transdermal drug delivery devices including a drug reservoir comprising drug in excess of saturation.
摘要翻译： 用于制造透皮药物递送装置和由其制成的装置的改进方法。 本发明提供了用于制造药物递送装置的热平衡过程，其不需要用药物预加载身体接触层。 该方法在制造透皮药物递送装置中具有特别的应用，其包括含有超过饱和的药物的药物储库。
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公开(公告)号：US4559222A
公开(公告)日：1985-12-17
申请号：US491490
申请日：1983-05-04
申请人： David J. Enscore , Robert M. Gale
发明人： David J. Enscore , Robert M. Gale
IPC分类号： A61K35/08 , A61K9/70 , A61F13/00 , A61K31/745 , A61L15/03
CPC分类号： A61K9/7053 , A61K9/7084
摘要： Mineral oil (MO) polyisobutylene (PIB), colloidal silicon dioxide (CSD) mixtures suitable for use as drug containing matrices in transdermal delivery systems are disclosed. Preferred systems for dispensing moderately mineral oil soluble drugs contain at least about 6% CSD, have a MO/PIB of at least 1.0 and a viscosity of at least 1.5.times.10.sup.7 poises. Preferred systems for dispensing clonidine have a clonidine permeability of at least 1.0.times.10.sup.-4 .mu.g/cm sec and a MO/PIB of at least 1.2.
摘要翻译： 公开了适用于透皮递送系统中含药基质的矿物油（MO）聚异丁烯（PIB），胶体二氧化硅（CSD）混合物。 用于分配适度矿物油溶性药物的优选系统含有至少约6％的CSD，具有至少1.0的MO / PIB和至少1.5×10 7泊的粘度。 用于分配可乐定的优选体系具有至少1.0×10 -4μg/ cm 2秒的可乐定渗透性和至少1.2的MO / PIB。
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9.发明授权
公开(公告)号：US4788062A
公开(公告)日：1988-11-29
申请号：US19162
申请日：1987-02-26
申请人： Robert M. Gale , David J. Enscore , Diane E. Nedberge , Melinda Nelson , Yu-Ling Cheng , Shari B. Libicki
发明人： Robert M. Gale , David J. Enscore , Diane E. Nedberge , Melinda Nelson , Yu-Ling Cheng , Shari B. Libicki
CPC分类号： A61K9/7053 , A61K31/565 , A61K31/57 , A61K47/14 , A61K47/26 , A61K9/0014 , A61K9/7076 , A61K9/7084
摘要： A transdermal delivery system for the administering of progesterone and an estradiol ester alone or in combination utilizing a polymer matrix having the drug(s) along with a permeation enhancer dispersed throughout.
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公开(公告)号：US6165497A
公开(公告)日：2000-12-26
申请号：US662857
申请日：1991-03-01
IPC分类号： A61K9/70 , A61K31/465 , A61F13/02 , A61F13/00
CPC分类号： A61K9/7084 , A61K9/7053 , A61K9/7069 , A61K31/465 , Y10S514/813
摘要： Rate controlled transdermal nicotine delivery systems are disclosed which utilize an in-line adhesive to maintain the systems on the skin. The initial equilibrated concentration of nicotine in the nicotine reservoir and the adhesive is below saturation, preferably at a thermodynamic activity no greater than 0.50, and the reservoir comprises the nicotine dissolved in a polymer with respect to which the rate controlling element of the device is substantially impermeable. In preferred embodiments the initial loading of nicotine in the reservoir is sufficient to prevent the activity of the nicotine in the reservoir from decreasing by more than about 75% and preferably no more than about 25% during the predetermined period of administration; and the thicknesses of the adhesive, rate controlling membrane and reservoir layers are selected so that at least 50% and, preferably at least 75% initial equilibrated nicotine loading is in the reservoir layer.
摘要翻译： 公开了速率控制的透皮尼古丁递送系统，其利用直列粘合剂将系统保持在皮肤上。 尼古丁储存器和粘合剂中尼古丁的初始平衡浓度低于饱和度，优选在不大于0.50的热力学活性下，并且储存器包括溶解在聚合物中的尼古丁，装置的速率控制元件基本上与其相对 不渗透 在优选的实施方案中，储存器中尼古丁的初始加载量足以防止储存器中的尼古丁的活性在给定的给药期间减少超过约75％，优选不超过约25％; 并且选择粘合剂，速率控制膜和储存器层的厚度，使得至少50％，优选至少75％的初始平衡的尼古丁负载在储层中。
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