公开(公告)号：US20080085298A1

公开(公告)日：2008-04-10

申请号：US11869724

申请日：2007-10-09

申请人： Roderike Pohl ,  Solomon Steiner

发明人： Roderike Pohl ,  Solomon Steiner

IPC分类号： A61K38/28 ,  A61K9/70 ,  A61P3/00

CPC分类号： A61K9/0056 ,  A61K9/006 ,  A61K9/06 ,  A61K9/107 ,  A61K38/28 ,  A61K47/12 ,  A61K47/183 ,  A61K2300/00

摘要： Gel, powder, suspension, emulsions or film formulations for systemic delivery of insulin with improved stability and rapid onset of action are described herein. The formulations are preferably absorbed to a mucosal surface, most preferably via buccal or sublingual administration, although rectal, vaginal, nasal or ocular administration is possible. The formulations contain insulin in combination with a chelator and dissolution agent, and optionally additional excipients. In the preferred embodiment, the formulation contains human insulin, a zinc chelator such as EDTA and a dissolution agent such as citric acid. Following administration, these formulations are rapidly absorbed into the blood stream. The formulation is preferably a polymeric gel, powder or film which adheres to the mucosal surface, thereby enhancing uptake of the incorporated drug. In the preferred embodiment, this formulation is administered sublingually, most preferably before a meal or after a meal.

摘要翻译： 本文描述了具有改善的稳定性和快速起效的胰岛素全身递送的凝胶，粉末，悬浮液，乳剂或膜制剂。 制剂优选被吸收到粘膜表面，最优选通过颊或舌下施用，尽管可以进行直肠，阴道，鼻或眼睛给药。 制剂含有与螯合剂和溶解剂以及任选的其它赋形剂组合的胰岛素。 在优选的实施方案中，制剂含有人胰岛素，锌螯合剂如EDTA和溶解剂如柠檬酸。 给药后，这些制剂被快速吸收到血液中。 制剂优选是粘附到粘膜表面的聚合物凝胶，粉末或膜，从而增强所掺入的药物的摄取。 在优选的实施方案中，该制剂是舌下给药，最优选在饭前或​​饭后服用的。

公开(公告)号：US20070191757A1

公开(公告)日：2007-08-16

申请号：US11675430

申请日：2007-02-15

申请人： Solomon Steiner ,  Robert Feldstein ,  Roderike Pohl ,  David Rhodes ,  Erik Steiner

发明人： Solomon Steiner ,  Robert Feldstein ,  Roderike Pohl ,  David Rhodes ,  Erik Steiner

IPC分类号： A61N1/30

CPC分类号： A61N1/306 ,  A61M2210/0625 ,  A61M2210/0643

摘要： Methods, devices and kits for sublingual drug delivery using iontophoresis are described herein. An active agent can be administered sublingually by placing a solid oral dosage form containing the active agent in the sublingual region of a patient and applying iontophoresis for a suitable period of time. Preferably up to 4 mA of current are applied to the sublingual region. Different time ranges can be used to administer iontophoresis; preferably iontophoresis is administered for up to 2 minutes at a time. Any suitable device for administering iontophoresis to the sublingual region may be used. The preferred device is a hand-held device that contains a handle, two electrodes, one of which is located on the handle and the other of which is attached to the end of the handle, and a connection to a power source. Optionally, the device contains a timer, which can be used turn off the current at a preset time. The device can be used to administer an active agent by iontophoresis to the sublingual region of a patient, by attaching the second electrode of the device to a solid oral dosage form containing the active agent to be administered. A kit contains the device for administering iontophoresis and one or more solid oral dosage forms, preferably in the form of one or more tabs or wafers. The tabs or wafers may be completely dissolvable or edible, or may contain a non-edible and non-dissolvable component. In a preferred embodiment, the solid oral dosage form contains insulin or an analog thereof and one or more excipients, preferably EDTA and citric acid.

摘要翻译： 本文描述了使用离子电渗法进行舌下药物递送的方法，装置和试剂盒。 可以通过将含有活性剂的固体口服剂型置于患者的舌下区域中并施用离子电渗疗法适当的时间段来向舌下施用活性剂。 优选地，最多将4mA的电流施加到舌下区域。 不同的时间范围可用于管理离子电渗疗法; 优选每次一次给予离子电渗疗法达2分钟。 可以使用用于向舌下区域施用离子电渗疗法的任何合适的装置。 优选的装置是手持装置，其包括手柄，两个电极，其中一个电极位于手柄上，另一个电极连接到手柄的端部，并且连接到电源。 可选地，设备包含定时器，其可以在预设时间关闭电流。 该装置可用于通过将装置的第二电极连接到含有待施用的活性剂的固体口服剂型，通过离子电渗法向患者的舌下区域施用活性剂。 试剂盒包含用于施用离子电渗疗法的装置和一种或多种固体口服剂型，优选以一个或多个片或晶片的形式。 标签或晶片可以是完全可溶的或可食用的，或者可以包含不可食用和不可溶的组分。 在优选的实施方案中，固体口服剂型含有胰岛素或其类似物和一种或多种赋形剂，优选EDTA和柠檬酸。

公开(公告)号：US20050155601A1

公开(公告)日：2005-07-21

申请号：US11037737

申请日：2005-01-18

申请人： Solomon Steiner ,  Craig Brown ,  Roderike Pohl ,  Trent Poole ,  Erik Steiner

发明人： Solomon Steiner ,  Craig Brown ,  Roderike Pohl ,  Trent Poole ,  Erik Steiner

IPC分类号： A61K9/14 ,  A61L9/04 ,  A61M11/00 ,  A61M15/00

CPC分类号： A61M11/00 ,  A61M15/0028 ,  A61M15/0048 ,  A61M15/0051 ,  A61M2202/064 ,  A61M2205/073 ,  A61M2205/8225

摘要： A drug delivery device that aerosolizes a dry powder formulation so that it forms a fine coating in the oral cavity and, more specifically, in the sublingual region of the oral cavity is described herein. In the preferred embodiment, the device contains five main parts: (i) a compressed gas canister, (ii) a dispenser body (also referred to herein as the main housing), (iii) a means for storing one or more doses of a drug formulation, (iv) a means for releasing a dose of the drug formulation such as a gas canister or spring piston and (v) a mouthpiece. Preferred configurations include circular, tubular, and rectangular. The means for storing the drug formulation may be configured to separately store one or more materials. In one embodiment, the means for storing the active agent is in the form of one or more drug discs, where the drug discs contain a plurality of blister packs, each storing one dose of the drug formulation. In another embodiment, the means for storing the active agent is a dosage cartridge containing a single dose of the drug formulation. In yet another embodiment, the drug formulation is stored on a ribbon containing a plurality of blister packs, each storing one dose of the drug formulation.

摘要翻译： 本文描述了使干燥粉末制剂气雾化以使其在口腔中，更具体地在口腔舌下区域中形成细小涂层的药物递送装置。 在优选实施例中，该装置包含五个主要部分：（i）压缩气体罐，（ii）分配器主体（在本文中也称为主壳体），（iii）用于存储一个或多个剂量的 药物制剂，（iv）用于释放剂量的药物制剂如气体罐或弹簧活塞的装置，（v）口器。 优选的构造包括圆形，管状和矩形。 用于储存药物制剂的方法可以被配置成分开存储一种或多种材料。 在一个实施方案中，用于储存活性剂的装置是一种或多种药物盘的形式，其中药物盘包含多个泡罩包装，每个存储一剂药物制剂。 在另一个实施方案中，用于储存活性剂的装置是含有单剂量药物制剂的剂量筒。 在另一个实施方案中，药物制剂储存在含有多个泡罩包装的条带上，每个存在一剂药物制剂。

公开(公告)号：US20080090753A1

公开(公告)日：2008-04-17

申请号：US11869693

申请日：2007-10-09

申请人： Roderike Pohl ,  Solomon Steiner

发明人： Roderike Pohl ,  Solomon Steiner

IPC分类号： A61K38/28 ,  A61P3/10

CPC分类号： A61K47/183 ,  A61K9/0056 ,  A61K38/28 ,  A61K47/12 ,  A61K2300/00

摘要： Injectable insulin formulations with improved stability and rapid onset of action are described herein. The formulations may be for subcutaneous, intradermal or intramuscular administration, In the preferred embodiment, the formulations are administered via subcutaneous injection. The formulations contain insulin in combination with a chelator and dissolution agent, and optionally additional excipients. In the preferred embodiment, the formulation contains human insulin, a zinc chelator such as EDTA and a dissolution agent such as citric acid. These formulations are rapidly absorbed into the blood stream when administered by subcutaneous injection. In the preferred embodiment, the insulin is provided as a dry powder in a sterile vial. This is mixed with a diluent containing a pharmaceutically acceptable carrier, such as water, a zinc chelator such as EDTA and a dissolution agent such as citric acid shortly before or at the time of administration. In another embodiment, the insulin is stored as a frozen mixture, ready for use upon thawing.

摘要翻译： 本文描述了具有改善的稳定性和快速起效的可注射的胰岛素制剂。 制剂可用于皮下，皮内或肌肉内给药。在优选的实施方案中，制剂通过皮下注射给药。 制剂含有与螯合剂和溶解剂以及任选的其它赋形剂组合的胰岛素。 在优选的实施方案中，制剂含有人胰岛素，锌螯合剂如EDTA和溶解剂如柠檬酸。 当通过皮下注射给药时，这些制剂被快速地吸收到血流中。 在优选的实施方案中，胰岛素以无菌小瓶中的干粉提供。 将其与包含药学上可接受的载体如水，锌螯合剂如EDTA的稀释剂和不久之前或给药时的溶解剂如柠檬酸混合。 在另一个实施方案中，将胰岛素作为冷冻混合物储存，准备在解冻时使用。

公开(公告)号：US20080047550A2

公开(公告)日：2008-02-28

申请号：US11037737

申请日：2005-01-18

申请人： Solomon Steiner ,  Craig Brown ,  Roderike Pohl ,  Trent Poole ,  Erik Steiner

发明人： Solomon Steiner ,  Craig Brown ,  Roderike Pohl ,  Trent Poole ,  Erik Steiner

IPC分类号： A61L9/04 ,  A61K9/14

CPC分类号： A61M11/00 ,  A61M15/0028 ,  A61M15/0048 ,  A61M15/0051 ,  A61M2202/064 ,  A61M2205/073 ,  A61M2205/8225

摘要： A drug delivery device that aerosolizes a dry powder formulation so that it forms a fine coating in the oral cavity and, more specifically in the sublingual region of the oral cavity is described herein. In the preferred embodiment, the device contains five main parts: (i) a compressed gas canister, (ii) a dispenser body (also referred to herein as the main housing ), (iii) a means for storing one or more doses of a drug formulation, (iv) a means for releasing a dose of the drug formulation such as a gas canister or spring piston and (v) a mouthpiece. Preferred configurations include circular, tubular, and rectangular. The means for storing the drug formulation may be configured to separately store one or more materials. In one embodiment, the means for storing the active agent is in the form of one or more drug discs, where the drug discs contain a plurality of blister packs, each storing one dose of the drug formulation. In another embodiment, the means for storing the active agent is a dosage cartridge containing a single dose of the drug formulation. In yet another embodiment, the drug formulation is stored on a ribbon containing a plurality of blister packs, each storing one dose of the drug formulation.

摘要翻译： 本文描述了使干燥粉末制剂雾化以使其在口腔中形成细小涂层并且更具体地在口腔的舌下区域中的药物递送装置。 在优选实施例中，该装置包含五个主要部分：（i）压缩气体罐，（ii）分配器主体（在本文中也称为主壳体），（iii）用于存储一个或多个剂量的 药物制剂，（iv）用于释放剂量的药物制剂如气体罐或弹簧活塞的装置，（v）口器。 优选的构造包括圆形，管状和矩形。 用于储存药物制剂的方法可以被配置成分开存储一种或多种材料。 在一个实施方案中，用于储存活性剂的装置是一种或多种药物盘的形式，其中药物盘包含多个泡罩包装，每个存储一剂药物制剂。 在另一个实施方案中，用于储存活性剂的装置是含有单剂量药物制剂的剂量筒。 在另一个实施方案中，药物制剂储存在含有多个泡罩包装的条带上，每个存在一剂药物制剂。

公开(公告)号：US20050214251A1

公开(公告)日：2005-09-29

申请号：US11077604

申请日：2005-03-11

申请人： Roderike Pohl ,  Solomon Steiner

发明人： Roderike Pohl ,  Solomon Steiner

IPC分类号： A61K9/00 ,  A61K9/14 ,  A61K9/20 ,  A61K9/48 ,  A61K38/00 ,  A61K38/18 ,  A61K38/19 ,  A61K38/20 ,  A61K38/22 ,  A61K38/23 ,  A61K38/26 ,  A61K38/27 ,  A61K38/28 ,  A61K38/29

CPC分类号： A61K9/006 ,  A61K9/0019 ,  A61K9/0056 ,  A61K38/28 ,  Y10S514/866 ,  Y10S514/951 ,  Y10S514/953 ,  Y10S514/959

摘要： Drug formulations for systemic drug delivery with improved stability and rapid onset of action are described herein. The formulations may be administered via buccal administration, sublingual administration, pulmonary delivery, nasal administration, subcutaneous administration, rectal administration, vaginal administration, or ocular administration. In the preferred embodiments, the formulations are administered sublingually or via subcutaneous injection. The formulations contain an active agent and one or more excipients, selected to increase the rate of dissolution. In the preferred embodiment, the drug is insulin, and the excipients include a metal chelator such as EDTA and an acid such as citric acid. Following administration, these formulations are rapidly absorbed by the oral mucosa when administered sublingually and are rapidly absorbed into the blood stream when administered by subcutaneous injection. In one embodiment, the composition is in the form of a dry powder. In another embodiment, the composition is in the form of a film, wafer, lozenge, capsule, or tablet. In a third embodiment, a dry powdered insulin is mixed with a diluent containing a pharmaceutically acceptable carrier, such as water or saline, a metal chelator such as EDTA and an acid such as citric acid. Devices for storing and mixing these formulations are also described.

摘要翻译： 本文描述了具有改善的稳定性和快速起效的全身药物递送的药物制剂。 制剂可以通过口腔给药，舌下给药，肺部输送，鼻内给药，皮下给药，直肠给药，阴道给药或眼部给药来施用。 在优选的实施方案中，制剂是舌下给药或通过皮下注射给药。 制剂含有活性剂和一种或多种赋形剂，其被选择以增加溶解速率。 在优选的实施方案中，药物是胰岛素，赋形剂包括金属螯合剂如EDTA和酸如柠檬酸。 给药后，这些制剂在舌下施用时被口腔粘膜快速吸收，并且当通过皮下注射给药时，其迅速地被吸收到血液流中。 在一个实施方案中，组合物为干粉的形式。 在另一个实施方案中，组合物为薄膜，晶片，锭剂，胶囊或片剂的形式。 在第三个实施方案中，将干粉状胰岛素与含有药学上可接受的载体如水或盐水，金属螯合剂如EDTA和酸如柠檬酸的稀释剂混合。 还描述了用于储存和混合这些制剂的装置。

公开(公告)号：US20120178675A1

公开(公告)日：2012-07-12

申请号：US13176435

申请日：2011-07-05

申请人： Roderike Pohl ,  Solomon Steiner ,  Robert Hauser ,  Richard Seibert ,  Ming Li

发明人： Roderike Pohl ,  Solomon Steiner ,  Robert Hauser ,  Richard Seibert ,  Ming Li

IPC分类号： A61K38/28 ,  A61P25/00 ,  A61P3/10

CPC分类号： C07K14/62 ,  A61K9/0019 ,  A61K38/28 ,  A61K47/183

摘要： Compositions and methods for modulating the pharmacokinetics and pharmacodynamics of rapid acting injectable insulin formulations are described herein. In the preferred embodiment, the formulations are administered via subcutaneous injection. The formulations contain insulin in combination with a zinc chelator such as ethylenediaminetetraacetic acid (“EDTA”) and a dissolution/stabilization agent, and optionally additional excipients. Calcium disodium EDTA is less likely to remove calcium from the body, and typically has less pain on injection in the subcutaneous tissue. Modulating the type and quantity of EDTA can change the insulin absorption profile. Increasing the quantity of citrate can further enhance absorption and chemically stabilize the formulation. In the preferred embodiment, the formulation contains human insulin, calcium disodium EDTA and a dissolution/stabilization agent such as citric acid or sodium citrate. These formulations are rapidly absorbed into the blood stream when administered by subcutaneous injection.

摘要翻译： 本文描述了用于调节快速作用的可注射胰岛素制剂的药代动力学和药效学的组合物和方法。 在优选的实施方案中，通过皮下注射施用制剂。 制剂含有与锌螯合剂如乙二胺四乙酸（“EDTA”）和溶解/稳定剂以及任选的其它赋形剂组合的胰岛素。 EDTA二钠不太可能从体内去除钙，并且通常在皮下组织中注射时疼痛较少。 调节EDTA的类型和数量可以改变胰岛素吸收特征。 增加柠檬酸盐的量可以进一步增强吸收和化学稳定制剂。 在优选的实施方案中，制剂含有人胰岛素，EDTA二钠钙和溶解/稳定剂如柠檬酸或柠檬酸钠。 当通过皮下注射给药时，这些制剂被快速地吸收到血流中。

公开(公告)号：US20080096800A1

公开(公告)日：2008-04-24

申请号：US11923591

申请日：2007-10-24

申请人： Roderike Pohl ,  Solomon Steiner

发明人： Roderike Pohl ,  Solomon Steiner

IPC分类号： A61K38/28 ,  A61P3/10

CPC分类号： A61K9/0056 ,  A61K9/006 ,  A61K9/06 ,  A61K9/107 ,  A61K38/28 ,  A61K47/12 ,  A61K47/18 ,  A61K47/183

摘要： Gel, powder, suspension, emulsions or film formulations for systemic delivery of insulin with improved stability and rapid onset of action are described herein. The formulations are preferably absorbed to a mucosal surface, most preferably via buccal or sublingual administration, although rectal, vaginal, nasal or ocular administration is possible. The formulations contain insulin in combination with a chelator and dissolution agent, and optionally additional excipients. In the preferred embodiment, the formulation contains human insulin, a zinc chelator such as EDTA and a dissolution agent such as citric acid. Following administration, these formulations are rapidly absorbed into the blood stream. The formulation is preferably a polymeric gel, powder or film which adheres to the mucosal surface, thereby enhancing uptake of the incorporated drug. In the preferred embodiment, this formulation is administered sublingually, most preferably before a meal or after a meal.

摘要翻译： 本文描述了具有改善的稳定性和快速起效的胰岛素全身递送的凝胶，粉末，悬浮液，乳剂或膜制剂。 制剂优选被吸收到粘膜表面，最优选通过颊或舌下施用，尽管可以进行直肠，阴道，鼻或眼睛给药。 制剂含有与螯合剂和溶解剂以及任选的其它赋形剂组合的胰岛素。 在优选的实施方案中，制剂含有人胰岛素，锌螯合剂如EDTA和溶解剂如柠檬酸。 给药后，这些制剂被快速吸收到血液中。 制剂优选是粘附到粘膜表面的聚合物凝胶，粉末或膜，从而增强所掺入的药物的摄取。 在优选的实施方案中，该制剂是舌下给药，最优选在饭前或​​饭后服用的。

公开(公告)号：US20070235365A1

公开(公告)日：2007-10-11

申请号：US11767698

申请日：2007-06-25

申请人： Roderike Pohl ,  Solomon Steiner

发明人： Roderike Pohl ,  Solomon Steiner

IPC分类号： A61K38/28 ,  A61K9/70 ,  B65D83/06

CPC分类号： A61K9/006 ,  A61K9/0019 ,  A61K9/0056 ,  A61K38/28 ,  Y10S514/866 ,  Y10S514/951 ,  Y10S514/953 ,  Y10S514/959

摘要： Drug formulations for systemic drug delivery with improved stability and rapid onset of action are described herein. The formulations may be administered via buccal administration, sublingual administration, pulmonary delivery, nasal administration, subcutaneous administration, rectal administration, vaginal administration, or ocular administration. In the preferred embodiments, the formulations are administered sublingually or via subcutaneous injection. The formulations contain an active agent and one or more excipients, selected to increase the rate of dissolution. In the preferred embodiment, the drug is insulin, and the excipients include a metal chelator such as EDTA and an acid such as citric acid. Following administration, these formulations are rapidly absorbed by the oral mucosa when administered sublingually and are rapidly absorbed into the blood stream when administered by subcutaneous injection. In one embodiment, the composition is in the form of a dry powder. In another embodiment, the composition is in the form of a film, wafer, lozenge, capsule, or tablet. In a third embodiment, a dry powdered insulin is mixed with a diluent containing a pharmaceutically acceptable carrier, such as water or saline, a metal chelator such as EDTA and an acid such as citric acid. Devices for storing and mixing these formulations are also described.

摘要翻译： 本文描述了具有改善的稳定性和快速起效的全身药物递送的药物制剂。 制剂可以通过口腔给药，舌下给药，肺部输送，鼻内给药，皮下给药，直肠给药，阴道给药或眼部给药来施用。 在优选的实施方案中，制剂是舌下给药或通过皮下注射给药。 制剂含有活性剂和一种或多种赋形剂，其被选择以增加溶解速率。 在优选的实施方案中，药物是胰岛素，赋形剂包括金属螯合剂如EDTA和酸如柠檬酸。 给药后，这些制剂在舌下施用时被口腔粘膜快速吸收，并且当通过皮下注射给药时，其迅速地被吸收到血液流中。 在一个实施方案中，组合物为干粉的形式。 在另一个实施方案中，组合物为薄膜，晶片，锭剂，胶囊或片剂的形式。 在第三个实施方案中，将干粉状胰岛素与含有药学上可接受的载体如水或盐水，金属螯合剂如EDTA和酸如柠檬酸的稀释剂混合。 还描述了用于储存和混合这些制剂的装置。

公开(公告)号：US20070086952A1

公开(公告)日：2007-04-19

申请号：US11537335

申请日：2006-09-29

申请人： Solomon Steiner ,  Roderike Pohl

发明人： Solomon Steiner ,  Roderike Pohl

IPC分类号： A61K38/28 ,  A61K9/12

CPC分类号： A61K38/28 ,  A61K9/0019 ,  A61K9/0031 ,  A61K9/0034 ,  A61K9/006 ,  A61K9/0075 ,  A61K9/0078 ,  A61K47/12 ,  A61K47/183

摘要： It has been discovered that by combining a chelator, such as ethylenediaminetetraacetic acid, with an acidifier, such as citric acid, the insulin is absorbed much more rapidly than in the absence of the chelator and acidifier, with a commercially available rapid, intermediate or long lasting insulin such as glargine, one can increase and/or prolong the bioavailability of the insulin mixture. The formulations are suitable for administration by injection or to a mucosal surface such as the pulmonary or oral regions, although subcutaneous injection is preferred.

摘要翻译： 已经发现，通过将诸如乙二胺四乙酸的螯合剂与酸化剂如柠檬酸组合，胰岛素比不含螯合剂和酸化剂的吸收要快得多，可商购的快速，中间或长期 持久的胰岛素如甘精胰岛素，可以增加和/或延长胰岛素混合物的生物利用度。 制剂适合于通过注射施用或粘膜表面如肺部或口腔区域，尽管皮下注射是优选的。