公开(公告)号：US20060165809A1

公开(公告)日：2006-07-27

申请号：US10522252

申请日：2003-07-28

申请人： Florence Guimberteau ,  Catherine Castan ,  Remi Meyrueix

发明人： Florence Guimberteau ,  Catherine Castan ,  Remi Meyrueix

IPC分类号： A61K9/50 ,  A61K9/16

CPC分类号： A61K9/5047 ,  A61K9/5015 ,  A61K9/5026 ,  A61K9/5078

摘要： The invention concerns microcapsules with prolonged release of active principles with low solubility, consisting of a core containing the active principle and coated with a polymer layer which controls the release of the active principle. The aim is that said oral microcapsules containing hardly soluble active principles should have a coating film of sufficient thickness to ensure controlled permeability and should be adapted to industrial reproduction. This is achieved by the inventive microcapsules of mean diameter less than 1000 microns, and whereof the coating film contains a film-forming polymer (P1) insoluble in gastrointestinal tract fluids, a water-soluble polymer (P2), a plasticizer (PL), and optionally a lubricating surfactant (TA). Said microcapsules are characterized in that their coating films represents at least 3% p/p of dry matter, relative to their total weight and their core contains a hardly soluble active principle and a solubilizing agent (polyoxyethylene hydrogenated castor oil) which provides the core wherein it is contained with properties such that the behaviour of the exposed core (non-coated) in a given dissolving test (TD), is as follows: release of 80% of active principle in less than two hours. The invention also concerns the use of such microcapsules in galenic formulation.

摘要翻译： 本发明涉及具有低溶解度的活性成分的延长释放的微胶囊，其由含有活性成分的核心组成并涂覆有控制活性成分释放的聚合物层。 目的是所述含有难溶性活性成分的口服微胶囊应具有足够厚度的涂膜，以确保受控的渗透性，并且应适于工业繁殖。 这通过本发明的平均直径小于1000微米的微胶囊实现，并且其中的涂膜含有不溶于胃肠道液体的成膜聚合物（P1），水溶性聚合物（P2），增塑剂（PL）， 和任选的润滑表面活性剂（TA）。 所述微胶囊的特征在于，它们的涂膜相对于它们的总重量表示至少3％的干物质的p / p，并且它们的芯含有难溶的活性成分和提供核的增溶剂（聚氧乙烯氢化蓖麻油），其中 含有这样的性质，使得在给定的溶解试验（TD）中暴露的芯（未涂覆）的行为如下：在少于两小时内释放80％的活性成分。 本发明还涉及这种微胶囊在盖仑制剂中的用途。

公开(公告)号：US20050175695A1

公开(公告)日：2005-08-11

申请号：US10997836

申请日：2004-11-24

申请人： Catherine Castan ,  Patrick Crowley ,  Florence Guimberteau ,  Remi Meyrueix ,  Chooh Oh ,  Gerard Soula

发明人： Catherine Castan ,  Patrick Crowley ,  Florence Guimberteau ,  Remi Meyrueix ,  Chooh Oh ,  Gerard Soula

IPC分类号： A61K20060101 ,  A61K9/16 ,  A61K9/22 ,  A61K9/50 ,  A61K31/403

CPC分类号： A61K9/1635 ,  A61K9/1641 ,  A61K9/1658 ,  A61K9/2077 ,  A61K31/403

摘要： The present invention also relates to carvedilol free base, carvedilol salts, anhydrous forms, or solvates thereof, corresponding pharmaceutical compositions or controlled release formulations, and delivery or dosing methods of carvedilol forms to the lower gastrointestingal tract or methods to treat cardiovascular diseases, which may include, but are not limited to hypertension, congestive heart failure, atherosclerosis, and angina. The present invention relates to controlled release formulations, which comprise various carvedilol forms, which may include, but are not limited to a carvedilol free base or corresponding carvedilol salts, anhydrous forms or solvates thereof.

摘要翻译： 本发明还涉及卡维地洛游离碱，卡维地洛盐，无水形式或其溶剂合物，相应的药物组合物或控释制剂，以及卡维地洛形式向下胃肠道输送或给药方法或治疗心血管疾病的方法， 包括但不限于高血压，充血性心力衰竭，动脉粥样硬化和心绞痛。 本发明涉及包含各种卡维地洛形式的控释制剂，其可以包括但不限于卡维地洛游离碱或相应的卡维地洛盐，无水形式或溶剂化物。

公开(公告)号：US20100266701A1

公开(公告)日：2010-10-21

申请号：US12560044

申请日：2009-09-15

申请人： Florence Guimberteau ,  Remi Meyrueix ,  Gerard Soula

发明人： Florence Guimberteau ,  Remi Meyrueix ,  Gerard Soula

IPC分类号： A61K9/14 ,  A61K31/52 ,  A61K31/155

CPC分类号： A61K9/5047 ,  A61K9/5078 ,  A61K31/196 ,  A61K31/522

摘要： The invention relates to solid microparticulate oral dosage forms having a composition that prevents the misuse of the active pharmaceutical ingredient (API) contained therein. The aim of the invention is to prevent the improper use of solid oral drugs for any use other than the therapeutic use(s) officially approved by the appropriate public health authorities. Another aim of the invention is to provide novel analgesic drugs which can be used to: prevent the misuse of, and addiction to certain analgesics and/or to control plasma concentration variability and/or to facilitate oral; administration; and/or to combine analgesics with one another and/or with one or more active ingredients in the same oral form. More specifically, the invention relates to a solid oral drug form comprising anti-misuse means and at least one active ingredient, which is characterized in that: at least part of the active ingredient is contained in microparticles; and the anti-misuse means comprise anti-crushing means (a) which enable the microparticles of the active ingredient to resist crushing, such as to prevent the misuse thereof. According to the invention, the drug form can also comprise means (b) for preventing the misuse of the active ingredient following a possible liquid extraction process.

摘要翻译： 本发明涉及具有防止滥用其中所含的活性药物成分（API）的组合物的固体微粒口服剂型。 本发明的目的是防止不适当地使用固体口服药物以用于由适当的公共卫生当局正式批准的治疗用途以外的任何用途。 本发明的另一个目的是提供新的止痛药，其可用于：防止某些止痛剂的滥用和成瘾和/或控制血浆浓度变异性和/或促进口服; 行政; 和/或将镇痛药彼此和/或以相同口服形式的一种或多种活性成分组合。 更具体地，本发明涉及包含抗滥用手段和至少一种活性成分的固体口服药物形式，其特征在于：至少部分活性成分包含在微粒中; 并且防误用手段包括能够使活性成分的微粒抵抗破碎的抗破碎装置（a），以防止其误用。 根据本发明，药物形式还可以包括用于防止在可能的液体提取过程后滥用活性成分的装置（b）。

公开(公告)号：US20090011028A1

公开(公告)日：2009-01-08

申请号：US12149541

申请日：2008-05-05

申请人： Frederic Checot ,  Cecile Bonnet-Gonnet ,  You-Ping Chan ,  Olivier Breyne ,  Remi Meyrueix

发明人： Frederic Checot ,  Cecile Bonnet-Gonnet ,  You-Ping Chan ,  Olivier Breyne ,  Remi Meyrueix

IPC分类号： A61K47/42 ,  A61K9/10 ,  A61K38/20

CPC分类号： A61K9/0019 ,  A61K9/10 ,  A61K9/1641 ,  A61K38/02 ,  A61K47/645 ,  A61K48/00

摘要： The present invention relates to novel pharmaceutical formulations for the release of an active principle (AP) over a sustained period of time of several days, or even several weeks.The invention relates, in a first aspect, to a liquid formulation comprising at least one active principle (AP) and an aqueous suspension based on colloïdal particles of a polymer (PO), wherein said formulation satisfies the following four conditions:(a) the polymer (PO) is a polyamino acid comprising glutamic residues, wherein some glutamic residues each carry a pendant cationic group (CG), said cationic groups being identical or different from one another, and other glutamic residues each carry a pendent hydrophobic group (GH), said hydrophobic groups (GH) being identical or different from one another, (b) the pHf value of the pH of said formulation is between 3.0 and 6.5; (c) at the pHf value, the polymer (PO) forms a colloïdal solution which associates spontaneously and noncovalently with the active principle (AP); (d) 1 ml of said formulation precipitates during mixing with a volume of 1 ml of a test buffer solution Tp. The invention also relates to a process for the preparation of such formulations and to a process for the preparation of medicaments including such formulations.

摘要翻译： 本发明涉及用于在持续的几天甚至几周的时间内释放活性成分（AP）的新型药物制剂。 本发明在第一方面涉及包含至少一种活性成分（AP）和基于聚合物（PO）的胶体颗粒的水性悬浮液的液体制剂，其中所述制剂满足以下四个条件：（a） 聚合物（PO）是包含谷氨酸残基的聚氨基酸，其中一些谷氨酸残基各自携带阳离子基团（CG），所述阳离子基团彼此相同或不同，并且其它谷氨酸残基各自携带悬垂疏水基团（GH） ，所述疏水基团（GH）彼此相同或不同，（b）所述制剂的pH值的pHf值为3.0至6.5; （c）在pHf值下，聚合物（PO）形成一种自发和非共价结合活性成分（AP）的胶体溶液; （d）1ml所述制剂在与1ml测试缓冲溶液Tp的体积混合期间沉淀。 本发明还涉及一种制备这些制剂的方法以及制备包括这些制剂的药物的方法。

公开(公告)号：US20050037077A1

公开(公告)日：2005-02-17

申请号：US10492129

申请日：2002-10-09

申请人： Valerie Legrand ,  Catherine Castan ,  Remi Meyrueix ,  Gerard Soula

发明人： Valerie Legrand ,  Catherine Castan ,  Remi Meyrueix ,  Gerard Soula

IPC分类号： A61K9/14 ,  A61K9/22 ,  A61K9/26 ,  A61K9/48 ,  A61K9/50 ,  A61K9/52 ,  A61K31/155 ,  A61K31/522 ,  A61K47/14 ,  A61K47/26 ,  A61K47/32 ,  A61K47/36 ,  A61K47/38 ,  A61P3/10 ,  A61P7/02 ,  A61P15/18 ,  A61P25/00 ,  A61P29/00 ,  A61P31/04 ,  A61P31/10 ,  A61P31/12

CPC分类号： A61K9/5078

摘要： The invention relates to a microparticulate system for the delayed and controlled release of active principles (AP) whose absorption window in vivo is essentially limited to the upper parts of the gastrointestinal tract, this system being intended for oral administration. The object of the invention is to provide a system ensuring that the AP is released with certainty by means of a dual mechanism of “time-dependent” and “pH-dependent” release. To achieve this object, the invention proposes a multimicrocapsular oral galenical form which is designed so as to guarantee therapeutic efficacy, and in which the release of the AP is governed by a dual release triggering mechanism that is “time-triggering” and “pH-triggering”. This system consists of microcapsules (200 to 600 μm) comprising a core of AP coated with a film (maximum 40% by weight) comprising a hydrophilic polymer A (Eudragit® L) and a hydrophobic compound B (vegetable wax, melting point=40-90° C.), B/A being between 0.2 and 1.5. These microcapsules have a dissolution behavior in vitro such that, at a constant pH of 1.4, a latency phase of between 1 and 5 hours is observed, followed by a release of the AP, and such that the change from pH 1.4 to pH 6.8 results in a release of the AP without a latency period in vitro.

摘要翻译： 本发明涉及一种用于延迟和控制释放活性成分（AP）的微粒体系，其活性成分在体内的吸收窗口基本上限于胃肠道的上部，该系统用于口服给药。 本发明的目的是提供一种确保通过“时间依赖”和“依赖于pH”释放的双重机制确定地释放AP的系统。 为了实现该目的，本发明提出了一种多微囊口服盖仑型，其设计以保证治疗功效，并且其中AP的释放由双时间触发机制（“触发时间”和“pH- 触发“。 该系统由包含涂覆有包含亲水性聚合物A（EudragitL）和疏水性化合物B（植物蜡，熔点）的膜（最大40重量％））的AP芯组成的微胶囊（200至600μm） = 40-90℃），B / A在0.2和1.5之间。 这些微胶囊在体外具有溶解行为，使得在1.4的恒定pH下，观察到1至5小时的潜伏期，随后释放AP，并且使得从pH1.4变为pH6.8的结果 在AP的释放中没有潜伏期在体外。

公开(公告)号：US5324827A

公开(公告)日：1994-06-28

申请号：US118286

申请日：1993-09-09

申请人： Yves Camberlin ,  Gerard Mignani ,  Remi Meyrueix ,  Gilles Tapolsky

发明人： Yves Camberlin ,  Gerard Mignani ,  Remi Meyrueix ,  Gilles Tapolsky

IPC分类号： C08F20/60 ,  C07D207/44 ,  C07D207/452 ,  C07D207/456 ,  C08F20/52 ,  C08F22/36 ,  C08F22/40 ,  C08G73/10 ,  C08G73/14 ,  G02F1/35 ,  G02F1/355 ,  G02F1/361 ,  G03F7/027 ,  C07C245/06

CPC分类号： C07D207/452 ,  C07D207/456 ,  C08G73/1067 ,  C08G73/14 ,  G02F1/361 ,  G03F7/027

摘要： Nonlinearly optically active monomer species comprising at least two carbon-carbon activated double bonds, i.e., the polymerization of which is facilitated by the presence of an electron attracting function, and a non-centrosymmetric system of pi (.pi.) conjugated bonds bearing at least one electron attracting group on one terminal thereof and at least one electron donor group on the other terminal, are readily (co)polymerized and optionally oriented and crosslinked into shaped articles well adopted for the manufacture of a variety of electrooptical devices; such monomer species can have, for example, the following structural formula (I): ##STR1##

摘要翻译： 包含至少两个碳 - 碳活化双键的非线性光学活性单体物质，即其聚合通过存在吸电子功能而促进，以及带有至少一个的π（π）共轭键的非中心对称体系 其一端上的吸电子基团和另一个末端上的至少一个电子给体基团容易（共）聚合并任选取向并交联成良好地用于制造各种电光器件的成形制品; 这样的单体物质可以具有例如以下结构式（I）：其中（I）

公开(公告)号：US08734850B2

公开(公告)日：2014-05-27

申请号：US10996780

申请日：2004-11-24

申请人： Catherine Castan ,  Florence Guimberteau ,  Remi Meyrueix ,  Gerard Soula

发明人： Catherine Castan ,  Florence Guimberteau ,  Remi Meyrueix ,  Gerard Soula

IPC分类号： A61K9/16 ,  A61K9/22

CPC分类号： A61K9/1635 ,  A61K9/1641 ,  A61K9/1658 ,  A61K9/2077 ,  A61K31/403

摘要： The field of the invention is that of oral pharmaceutical medicinal products or compositions, more particularly of the type of those comprising one or more active principles.The aim of the invention is to provide an improved oral medicinal product that can be administered in one or more daily doses, with modified release of active principle (in particular an active principle), for improving the prophylactic and therapeutic efficacy of such a medicinal product.This aim is achieved by means of the multimicrocapsular oral pharmaceutical form according to the invention in which the release of the AP is controlled by means of a double mechanism of triggering the release: “time triggering” and “pH triggering”. This medicinal product comprises microcapsules with modified release of active principle, each containing a core comprising the active principle and one or more swelling agents, and at least one coating making possible the modified release of the active principle.

摘要翻译： 本发明的领域是口服药物药物产品或组合物的领域，更特别是包含一种或多种活性成分的那些类型。 本发明的目的是提供一种改进的口服药物产品，其可以以一种或多种日剂量施用，具有改进的活性成分释放（特别是活性成分），用于改善这种药物的预防和治疗功效 。 该目的通过根据本发明的多微囊口服药物形式实现，其中AP的释放通过触发释放的双重机制来控制：“时间触发”和“pH触发”。 这种药用产品包括具有活性成分释放的微胶囊，每个微胶囊含有包含活性成分的核心和一种或多种溶胀剂，以及至少一种使活性成分的修饰释放成为可能的涂层。

公开(公告)号：US08236353B2

公开(公告)日：2012-08-07

申请号：US12149541

申请日：2008-05-05

申请人： Frédéric Checot ,  Cecile Bonnet-Gonnet ,  You-Ping Chan ,  Olivier Breyne ,  Remi Meyrueix

发明人： Frédéric Checot ,  Cecile Bonnet-Gonnet ,  You-Ping Chan ,  Olivier Breyne ,  Remi Meyrueix

IPC分类号： A61K9/14 ,  A61K9/64 ,  A61K9/58 ,  A61K38/00 ,  A61K9/52

CPC分类号： A61K9/0019 ,  A61K9/10 ,  A61K9/1641 ,  A61K38/02 ,  A61K47/645 ,  A61K48/00

摘要： The present invention relates to pharmaceutical formulations for the release of an active principle (AP) over a sustained period of time. The invention relates to a liquid formulation comprising at least one active principle (AP) and an aqueous suspension based on colloidal particles of a polymer (PO), wherein said formulation satisfies the following four conditions: (a) the PO is a polyamino acid comprising glutamic residues, wherein some glutamic residues each carry a pendant cationic group (CG), said CG being identical or different from one another, and other glutamic residues each carry a pendent hydrophobic group (GH), said GH being identical or different from one another, (b) the pHf value of the pH of said formulation is between 3.0 and 6.5; (c) at the pHf value, the PO forms a colloidal solution which associates spontaneously and noncovalently with the AP; (d) 1 ml of said formulation precipitates during mixing with a volume of 1 ml of a test buffer solution Tp.

摘要翻译： 本发明涉及用于在持续时间内释放活性成分（AP）的药物制剂。 本发明涉及包含至少一种活性成分（AP）和基于聚合物（PO）的胶体颗粒的水性悬浮液的液体制剂，其中所述制剂满足以下四个条件：（a）PO是聚氨基酸，其包含 谷氨酸残基，其中一些谷氨酸残基各自携带阳离子基团（CG），所述CG彼此相同或不同，其他谷氨酸残基各自携带悬垂疏水基团（GH），所述GH彼此相同或不同 ，（b）所述制剂的pH值的pHf值为3.0至6.5; （c）在pHf值下，PO形成胶体溶液，其与AP自发地和非共价结合; （d）1ml所述制剂在与1ml测试缓冲溶液Tp的体积混合期间沉淀。

公开(公告)号：US08197850B2

公开(公告)日：2012-06-12

申请号：US10415850

申请日：2001-11-19

申请人： Catherine Castan ,  Remi Meyrueix ,  Gerard Soula

发明人： Catherine Castan ,  Remi Meyrueix ,  Gerard Soula

IPC分类号： A61K9/14

CPC分类号： A61K31/155 ,  A61K9/5015 ,  A61K9/5047 ,  A61K31/00

摘要： The invention concerns an oral galenic form for prolonged release of anti-hyperglycaemic (metformin) active principles. Said medicine enables to obtain an efficient therapeutic protection over 24 hours by overcoming the problems of bypass of the absorption window and the massive localised release of active principles. Therefor, said medicine comprises several thousand anti-hyperglycaemic (metformin) microcapsules each consisting of a core comprising at least an anti-hyperglycaemic agent and of a coating film applied on the core and enabling the prolonged release in vivo of the anti-hyperglycaemic agent. Said microcapsules have a grain size distribution ranging between 50 and 100 microns. The reproducibility of the transit kinetics and hence of bioavailability are very high. There results for the patient a lesser risk of hyperglycaemic or hypoglycaemic. The invention also concerns the preparation of said medicine and the use of a plurality of said microcapsules for making an anti-hyperglycaemic medicine. The invention is applicable to the treatment of type II diabetes.

摘要翻译： 本发明涉及用于延长释放抗高血糖（二甲双胍）活性成分的口服盖仑制剂。 所述药物通过克服吸收窗旁路的问题和主动原理的大量局部释放，能够在24小时内获得有效的治疗保护。 因此，所述药物包含数千种抗高血糖（二甲双胍）微胶囊，每个微胶囊由包含至少抗高血糖剂的芯和涂覆在芯上的涂膜构成，并且能够在体内延长抗高血糖剂的释放。 所述微胶囊具有在50和100微米之间的粒度分布。 运输动力学和生物利用度的重现性非常高。 结果，患者血糖过低或低血糖的风险较小。 本发明还涉及所述药物的制备以及多种所述微胶囊用于制备抗高血糖药物的用途。 本发明适用于II型糖尿病的治疗。

公开(公告)号：US20080026056A1

公开(公告)日：2008-01-31

申请号：US11631030

申请日：2005-05-25

申请人： Florence Guimberteau ,  Catherine Castan ,  Remi Meyrueix ,  Gerard Soula

发明人： Florence Guimberteau ,  Catherine Castan ,  Remi Meyrueix ,  Gerard Soula

IPC分类号： A61K9/50 ,  A61K31/43 ,  A61P31/04

CPC分类号： A61K9/5084 ,  A61K9/5047 ,  A61K31/43

摘要： The invention relates to oral antibiotic drugs. The object of the invention is to limit or even stop the increase in antibiotic resistance without sacrificing the requirements of (a) increased efficacy of oral antibiotics, particularly for pediatric applications, (b) tolerance, (c) broad spectra of activity, and (d) good patient compliance. This object is achieved by the invention, which proposes the use of modified-release microcapsules, comprising a core that contains at least one active principle AP1 formed of at least one antibiotic, and a coating for said core that governs the modified release of said active principle, for the manufacture of a drinkable or orally dispersible antibiotic pharmaceutical formulation that makes it possible to limit the increase in the antibiotic resistance of the target germs, this formulation being: capable of administration in one or two, preferably two, intakes per day, and definable as follows, relative to an immediate-release oral formulation (IRF*) comprising at least one active principle API, and for the same dose D of API as IRF*: Tmic>T*micof IRF*

摘要翻译： 本发明涉及口服抗生素药物。 本发明的目的是限制或甚至阻止抗生素耐药性的增加，而不会牺牲（a）口服抗生素的功效增加，特别是儿科应用的要求，（b）耐受性，（c）活性的广谱谱和（ d）良好的患者依从性。 该目的是通过本发明来实现的，本发明提出使用包含至少一种由至少一种抗生素形成的至少一种活性成分AP1的芯的改性释放微胶囊和用于所述核心的涂层，所述涂层控制所述活性物质的修饰释放 原理，用于制造可以限制目标细菌的抗生素抗性增加的可饮用或口服分散的抗生素药物制剂，该制剂是：能够每天摄入一次或两次，优选两次， 并且可定义如下，相对于包含至少一种活性成分API的立即释放口服制剂（IRF *），和与IRF *相同的API剂量D：<？in-line-formula description =“In-line IRF *的公式“end =”lead“？> T > T * 在线公式描述=”在线公式“end =” 尾巴“？>