公开(公告)号：US09168498B2

公开(公告)日：2015-10-27

申请号：US12092308

申请日：2006-10-13

Applicant: Rainer Helmut Müller ,  Jan Möschwitzer

Inventor： Rainer Helmut Müller ,  Jan Möschwitzer

IPC: B01J13/02 ,  B01J2/00 ,  B01F5/02 ,  B01F5/04 ,  B01F5/06 ,  B01F11/02 ,  B01F15/02 ,  B01J2/02 ,  B01J2/18 ,  B01F7/00

CPC classification number: B01J2/003 ,  B01F5/0256 ,  B01F5/0451 ,  B01F5/0646 ,  B01F5/0647 ,  B01F5/0652 ,  B01F5/0685 ,  B01F7/00775 ,  B01F11/0258 ,  B01F15/0203 ,  B01J2/02 ,  B01J2/18

Abstract: Disclosed are methods and devices for producing very fine particles which are then coated with protective polymers in another step of the process. The particles are produced using a method in which a liquid flow comprising a particle-free liquid 1 that contains the active substance in a dissolved form is combined with a second liquid flow comprising a liquid 2 in a high-energy zone or no sooner than two seconds before reaching the high-energy zone. Said two liquids can be mixed with each other while the active substance dissolved in liquid 1 is insoluble or more difficult to dissolve in liquid 2 than in liquid 1 and settles in the form of particles in the high-energy zone or within a maximum of 2 seconds before reaching the high-energy zone when the two liquids are mixed. The obtained particles are introduced into an aqueous outer phase which contains the coating materials in a dissolved form and are then subjected to a drying step such that said materials settle on the particles as a closed coating. The coated particles are protected from damaging influences and are provided with modified release kinetics compared to uncoated particles.

Abstract translation: 公开了用于生产非常细的颗粒的方法和装置，然后在该方法的另一步骤中用保护性聚合物涂覆。 使用这样的方法制备颗粒，其中将包含溶解形式的活性物质的无颗粒液体1的液体流与包含高能区域中的液体2或不超过两个的第二液流组合 秒到达高能区。 所述两种液体可以彼此混合，而溶解在液体1中的活性物质不溶于或更难溶解在液体2中而不是液体1中，并且以高能区域中的颗粒形式或最大值为2 当两种液体混合时达到高能区之前秒钟。 将所得颗粒引入包含溶解形式的涂层材料的水性外相中，然后进行干燥步骤，使得所述材料作为封闭涂层沉积在颗粒上。 保护涂覆的颗粒免受损伤影响，并且与未涂覆的颗粒相比具有改性释放动力学。

公开(公告)号：US20090297565A1

公开(公告)日：2009-12-03

申请号：US12092308

申请日：2006-10-13

Applicant: Rainer Helmut Müller ,  Jan Möschwitzer

Inventor： Rainer Helmut Müller ,  Jan Möschwitzer

IPC: A61K9/14 ,  A61K9/00 ,  B05C19/02

CPC classification number: B01J2/003 ,  B01F5/0256 ,  B01F5/0451 ,  B01F5/0646 ,  B01F5/0647 ,  B01F5/0652 ,  B01F5/0685 ,  B01F7/00775 ,  B01F11/0258 ,  B01F15/0203 ,  B01J2/02 ,  B01J2/18

Abstract: Disclosed are methods and devices for producing very fine particles which are then coated with protective polymers in another step of the process. The particles are produced using a method in which a liquid flow comprising a particle-free liquid 1 that contains the active substance in a dissolved form is combined with a second liquid flow comprising a liquid 2 in a high-energy zone or no sooner than two seconds before reaching the high-energy zone. Said two liquids can be mixed with each other while the active substance dissolved in liquid 1 is insoluble or more difficult to dissolve in liquid 2 than in liquid 1 and settles in the form of particles in the high-energy zone or within a maximum of 2 seconds before reaching the high-energy zone when the two liquids are mixed. The obtained particles are introduced into an aqueous outer phase which contains the coating materials in a dissolved form and are then subjected to a drying step such that said materials settle on the particles as a closed coating. The coated particles are protected from damaging influences and are provided with modified release kinetics compared to uncoated particles.

Abstract translation: 公开了用于生产非常细的颗粒的方法和装置，然后在该方法的另一步骤中用保护性聚合物涂覆。 使用这样的方法制备颗粒，其中将包含溶解形式的活性物质的无颗粒液体1的液体流与包含高能区域中的液体2或不超过两个的第二液流组合 秒到达高能区。 所述两种液体可以彼此混合，而溶解在液体1中的活性物质不溶于或更难溶解在液体2中而不是液体1中，并且以高能区域中的颗粒形式或最大值为2 当两种液体混合时达到高能区之前秒钟。 将所得颗粒引入包含溶解形式的涂层材料的水性外相中，然后进行干燥步骤，使得所述材料作为封闭涂层沉积在颗粒上。 保护涂覆的颗粒免受损伤影响，并且与未涂覆的颗粒相比具有改性释放动力学。

公开(公告)号：US06551619B1

公开(公告)日：2003-04-22

申请号：US09674417

申请日：2001-01-22

Applicant: Lawrence John Penkler ,  Rainer Helmut Müller ,  Stephan Anton Runge ,  Vittorino Ravelli

Inventor： Lawrence John Penkler ,  Rainer Helmut Müller ,  Stephan Anton Runge ,  Vittorino Ravelli

IPC: A61K914

CPC classification number: A61K9/5123 ,  A61K9/1075 ,  A61K9/1617 ,  A61K38/13 ,  Y10S514/951 ,  Y10S514/969 ,  Y10S514/975 ,  Y10S977/906

Abstract: The invention relates to solid, particulate lipid-based excipients which are loaded with cyclosporine. Said excipients have improved biopharmaceutical properties for cyclosporines in vivo, are of a better quality (in terms of fineness, homogeneity of the particles, inclusion of the medicament) and are more physically stable in the particulate formulation (no aggregation or gel formation). The invention also relates to a therapeutic treatment with cyclosporine formulations which produce an average blood level concentration in the steady state range of 300 ng/ml to over 1000 ng/ml, preferably over 800 ng/ml, especially up to 900 ng/ml, preferably 400 ng/ml to 800 ng/ml in the absence of high initial blood level concentrations essentially over 1500 ng/ml, especially over 1200 ng/ml. This blood level concentration is preferably maintained for an extended period of at least 5 hours, preferably at least 7 hours.

Abstract translation: 本发明涉及负载有环孢菌素的固体颗粒状基于脂质的赋形剂。 所述赋形剂在体内具有改善的环孢菌素的生物药物性质，具有更好的质量（在细度，颗粒的均匀性，药物的包合性方面），并且在颗粒制剂中更具物理稳定性（无聚集或凝胶形成）。 本发明还涉及使用环孢菌素制剂的治疗性治疗，其在300ng / ml至超过1000ng / ml，优选超过800ng / ml，特别是至多900ng / ml的稳态范围内产生平均血液浓度， 优选400ng / ml至800ng / ml，在不存在高的初始血液浓度基本上超过1500ng / ml，特别是超过1200ng / ml的情况下。 该血液浓度优选保持至少5小时，优选至少7小时的延长时间。