公开(公告)号：US08895063B2

公开(公告)日：2014-11-25

申请号：US11651577

申请日：2007-01-10

Applicant: Florence Guimberteau ,  Frederic Dargelas ,  Gérard Soula ,  Rémi Soula

Inventor： Florence Guimberteau ,  Frederic Dargelas ,  Gérard Soula ,  Rémi Soula

IPC: A61K8/20 ,  A61K9/50 ,  A61K45/06 ,  A61K33/30 ,  A61K33/26 ,  A61K33/06 ,  A61K9/48

CPC classification number: A61K9/5047 ,  A61K9/4825 ,  A61K9/5078 ,  A61K9/5084 ,  A61K33/06 ,  A61K33/26 ,  A61K33/30 ,  A61K45/06 ,  A61K2300/00

Abstract: An oral solid dosage form containing one or several active principle(s) having analgesic properties, the composition of said dosage form being such that it prevents the misuse of said dosage form through the liquid extraction of the active principle(s) contained therein, using commonly available solvents.Said oral solid dosage form containing at least one salt of at least one analgesic active principle, and an anti-misuse system comprising at least one quenching agent, said quenching agent being suitable for inducing complexation of said analgesic active principle salt when the analgesic active principle salt is improperly extracted, notably by a drug abuser, in vitro in solution from said oral solid dosage form.

Abstract translation: 含有一种或多种具有止痛特性的活性成分的口服固体剂型，所述剂型的组成使得其通过液体提取其中包含的活性成分来防止所述剂型的滥用，其使用 常用的溶剂。 所述口服固体剂型含有至少一种至少一种止痛活性成分的盐，以及包含至少一种猝灭剂的抗滥用系统，所述猝灭剂适合于诱导所述止痛活性成分盐在所述止痛活性成分 在所述口服固体剂型的溶液中，盐不适当地提取，特别是药物滥用者。

公开(公告)号：US07709445B2

公开(公告)日：2010-05-04

申请号：US10473821

申请日：2002-03-26

Applicant: Gérard Soula ,  Nathan Bryson

Inventor： Gérard Soula ,  Nathan Bryson

IPC: A61K38/02 ,  A61K9/10

CPC classification number: A61K9/5146 ,  A61K9/1075 ,  Y10S514/937 ,  Y10S514/941

Abstract: An aqueous suspension, stable in physiological medium, of nanoparticles for delivering active principles such as insulin. The delivery particles are based on a three-block copolymer: polyethylene glycol/hydrophilic polyaminoacid/hydrophobic polyaminoacid. These three-block copolymers can be associated with an active principle without denaturing it, and perform a controlled and long-term release of the active principle in vivo, and thus provide the active principle with a very prolonged release. Also disclosed is a powder form solid from which are derived the delivery particles, the preparation of the powder-form solid, a suspension of delivery particles based on the three-block copolymer, and pharmaceutical specialties obtainable from the delivery particles filled with active principle.

Abstract translation: 在生理介质中稳定的水性悬浮液用于递送活性成分如胰岛素的纳米颗粒。 递送颗粒基于三嵌段共聚物：聚乙二醇/亲水性聚氨基酸/疏水性聚氨基酸。 这些三嵌段共聚物可以与活性成分相关联而不使其变性，并且在体内进行活性成分的受控和长期释放，从而提供非常长期释放的活性成分。 还公开了一种粉末状固体，其衍生为递送颗粒，粉末状固体的制备，基于三嵌段共聚物的递送颗粒的悬浮液，以及可从填充有活性成分的递送颗粒获得的药物特性。

公开(公告)号：US07678882B2

公开(公告)日：2010-03-16

申请号：US11509783

申请日：2006-08-25

Applicant: Stéphanie Angot ,  Olivier Breyne ,  You-Ping Chan ,  Gérard Soula

Inventor： Stéphanie Angot ,  Olivier Breyne ,  You-Ping Chan ,  Gérard Soula

IPC: C07K2/00

CPC classification number: A61Q19/00 ,  A61K8/88 ,  A61K47/34 ,  A61K47/645 ,  A61K47/65 ,  C08G69/10 ,  C08G69/48

Abstract: The invention relates to novel materials based on biodegradable polyamino acids that are useful for vectorizing active principle(s)(AP). The aim of the invention is to supply a new polymeric raw material that is used for vectorizing AP and optimally fulfills all requirements concerning biocompatibility, biodegradability, the ability to be easily associated with numerous active principles or solubilize the active principles and to release the active principles in vivo. Such polymers can also be readily and economically transformed into particles vectorizing active principles according to the grafting rate of the hydrophobic groups, said particles being able to form stable aqueous colloidal suspensions. The aim of the invention is achieved by the inventive amphiphile polyamino acids comprising aspartic and/or glutamic units that carry grafts which encompass at least one hydrophobic unit and are linked to the aspartic and/or glutamic units via a rotula containing two amide functions, more particularly via a spacer of the lysine or ornithine type. The amide functions ensure better stability during hydrolysis than comparable products known in prior art. The invention also relates to new pharmaceutical, cosmetic, dietetic, or phytosanitary compositions based on the inventive polyamino acids.

Abstract translation: 本发明涉及可用于向量化活性成分（AP）的可生物降解的聚氨基酸的新型材料。 本发明的目的是提供一种新的聚合物原料，其用于向AP进行载体化，并且最佳地满足关于生物相容性，生物可降解性，易于与许多活性成分相关联或增溶活性成分的能力的所有要求，并释放活性成分 体内。 这样的聚合物也可以容易地和经济地转化成根据疏水基团的接枝速率向量化活性成分的颗粒，所述颗粒能够形成稳定的水性胶态悬浮液。 本发明的目的是通过包含天冬氨酸和/或谷氨酸单元的本发明的两亲性聚氨基酸实现的，所述天然氨基酸和/或谷氨酸单元携带包含至少一个疏水单元的移植物，并通过含有两个酰胺官能团的转运体与天冬氨酸和/或谷氨酸单元连接 特别是通过赖氨酸或鸟氨酸类型的间隔物。 酰胺功能确保在水解期间比现有技术中已知的可比产品更好的稳定性。 本发明还涉及基于本发明的聚氨基酸的新的药物，化妆品，饮食或植物检疫组合物。

公开(公告)号：US20100009005A1

公开(公告)日：2010-01-14

申请号：US11920749

申请日：2006-05-24

Applicant: Gérard Soula ,  Florence Guimberteau

Inventor： Gérard Soula ,  Florence Guimberteau

IPC: A61K9/50 ,  A61K31/60 ,  A61P29/00

CPC classification number: A61K9/5084 ,  A61K9/1652 ,  A61K9/1676 ,  A61K9/5026 ,  A61K9/5047 ,  A61K31/60 ,  A61K45/06 ,  A61K2300/00

Abstract: The invention relates to pharmaceutical compositions of acetylsalicylic acid-based microcapsules to selectively inhibit the COX in the portal vein and/or in the liver to reduce the production of thromboxane. Further, the pharmaceutical composition minimizes COX inhibition in the systemic circulation to optimize the inhibition of platelet aggregation. Certain embodiments also address methods of prevention and/or treatment of these diseases, using these oral compositions such as enhancing the safety of antithrombotic treatments. Other embodiments contemplate oral pharmaceutical compositions that combine acetylsalicylic acid with anti-platelet aggregation drugs, without inducing gastric side effects.

Abstract translation: 本发明涉及基于乙酰水杨酸的微胶囊的药物组合物，以选择性地抑制门静脉和/或肝脏中的COX以减少血栓素的产生。 此外，药物组合物使全身循环中的COX抑制最小化，以优化血小板聚集的抑制。 某些实施方案还涉及使用这些口服组合物来预防和/或治疗这些疾病的方法，例如增强抗血栓治疗的安全性。 其它实施方案考虑了将乙酰水杨酸与抗血小板聚集药物组合的口服药物组合物，而不诱导胃副作用。

公开(公告)号：US20130065826A1

公开(公告)日：2013-03-14

申请号：US13571026

申请日：2012-08-09

Applicant: Olivier SOULA ,  Gérard SOULA ,  Jeff TONNAR

Inventor： Olivier SOULA ,  Gérard SOULA ,  Jeff TONNAR

IPC: A61K38/28 ,  A61P3/10

CPC classification number: A61K38/28 ,  A61K9/0019 ,  A61K9/08 ,  A61K31/721 ,  A61K38/26 ,  A61K47/36 ,  A61K2300/00

Abstract: A composition in the form of an injectable aqueous solution, the pH of which is between 6.0 and 8.0, includes at least a basal insulin, the isoelectric point pI of which is between 5.8 and 8.5; and a dextran substituted by radicals carrying carboxylate charges and hydrophobic radicals. Single-dose formulations at a pH of between 7 and 7.8 includes a basal insulin whose isoelectric point is between 5.8 and 8.5 and a prandial insulin.

Abstract translation: pH为6.0-8.0的可注射水溶液形式的组合物至少包含基础胰岛素，其等电点pI在5.8和8.5之间; 和由携带羧酸酯电荷和疏水基团的基团取代的葡聚糖。 pH7-7.8之间的单剂量制剂包括等电点为5.8-8.5之间的基础胰岛素和餐前胰岛素。

公开(公告)号：US07659365B2

公开(公告)日：2010-02-09

申请号：US10574475

申请日：2004-09-28

Applicant: Rémi Soula ,  You-Ping Chan ,  Gérard Soula ,  Olivier Breyne

Inventor： Rémi Soula ,  You-Ping Chan ,  Gérard Soula ,  Olivier Breyne

IPC: C07K14/00

CPC classification number: A61K8/88 ,  A61K9/1075 ,  A61K9/5146 ,  A61K47/34 ,  A61K47/645 ,  A61Q19/00 ,  C08G69/10 ,  C08G73/028 ,  C08L79/02

Abstract: The invention relates to novel materials based on biodegradable homopolyamino acids and which can be used for the vectorization of (an) active ingredient(s) (AI). The invention also relates to novel pharmaceutical, cosmetic, dietetic or phytosanitaty compositions based on homopolyamino acids. The invention can produce a novel polymer raw material which can be used for the vectoiization of Al that can optimally be: biocompatible, biodegradable, capable of becoming easily associated with a large number of active ingredients or solubilizing them and releasing the active ingredients in vivo. According to the present invention, which primarily relates to linear homopolyamino acids having aspartic or glutamic units and whose attachments can include hydrophobic groups having 8-30 carbon atoms. The homopolymers are amphiphilic and anionic and can easily be transformed at low cost into particles for the vectorization of active ingredients. The particles can form stable aqueous colloidal suspensions.

Abstract translation: 本发明涉及基于可生物降解的均聚氨基酸的新型材料，其可用于（a）活性成分（AI）的向量化。 本发明还涉及基于均聚氨基酸的新型药物，化妆品，饮食或植物营养成分。 本发明可以生产出一种新型的聚合物原料，它可以用于最佳的生物相容性，生物降解性，能够容易地与大量活性成分缔合或溶解它们并在体内释放活性成分的Al的促进作用。 根据本发明，其主要涉及具有天冬氨酸或谷氨酸单元的线性均聚氨基酸，并且其连接物可以包括具有8-30个碳原子的疏水基团。 均聚物是两亲性的和阴离子的，并且可以容易地以低成本转化成用于活性成分载体化的颗粒。 颗粒可以形成稳定的水性胶体悬浮液。

公开(公告)号：US20090311315A1

公开(公告)日：2009-12-17

申请号：US11884549

申请日：2006-02-21

Applicant: Catherine Castan ,  Florence Guimberteau ,  Rémi Meyrueix ,  Gérard Soula

Inventor： Catherine Castan ,  Florence Guimberteau ,  Rémi Meyrueix ,  Gérard Soula

IPC: A61K9/52 ,  A61K9/14 ,  A61K9/22 ,  A61K31/4178 ,  A61K31/4184 ,  A61K9/26

CPC classification number: A61K9/2081 ,  A61K9/5073 ,  A61K9/5078 ,  A61K9/5084 ,  A61K31/415 ,  A61K31/417

Abstract: The invention relates to oral pharmaceutical forms with modified release of ARB, and to related treatments and delivery methods.The invention concerns a form with modified release of ARB which prolongs the bioabsorption time and enables the pharmaceutical form to be administered only once daily.Therefore, the invention is an oral pharmaceutical form with modified ARB release comprising a plurality of ARB microunits (mean diameter: 50-1000 μm) leading, after being taken, to a plasma profile wherein C18 h*≦C18 h, with C18 h=plasma ARB concentration, 18 h after being taken, C18 h*=plasma ARB concentration corresponding to C18 h and obtained under the same conditions as C18 h, with a reference immediate-release oral pharmaceutical form*, containing the same dose of ARB, Cmax=maximum plasma ARB concentration after being taken, Cmax*=maximum plasma ARB concentration corresponding to Cmax and obtained under the same conditions as Cmax, with a reference immediate-release oral pharmaceutical form*, containing the same dose of ARB.

Abstract translation: 本发明涉及具有ARB修饰释放的口服药物形式，以及相关治疗和递送方法。 本发明涉及延长生物吸收时间并延长药物形式每天只能施用一次的ARB的释放形式。 因此，本发明是具有改良的ARB释放的口服药物形式，其包含多个ARB微单位（平均直径：50-1000μm），其被引导至血浆曲线，其中C18h * <= C18h，C18h =血浆ARB浓度，服用18小时后，C18h * =对应于C18h的血浆ARB浓度，并且在与C18h相同的条件下获得，含有相同剂量的ARB的参考速释口服药物形式* Cmax =服用后最大血浆ARB浓度，Cmax * =对应于Cmax的最大血浆ARB浓度，并且在与Cmax相同的条件下获得，含有相同剂量的ARB的参考即释释口服药物形式*。

公开(公告)号：US06630171B1

公开(公告)日：2003-10-07

申请号：US09856378

申请日：2001-07-06

Applicant: Sylvain Huille ,  Florence Nicolas ,  Nathan Brison ,  Gérard Soula

Inventor： Sylvain Huille ,  Florence Nicolas ,  Nathan Brison ,  Gérard Soula

IPC: A61K914

CPC classification number: A61K9/5146 ,  A61K8/0241 ,  A61K8/88 ,  A61K9/1075 ,  A61K9/1641 ,  A61K2800/10 ,  A61K2800/412 ,  A61K2800/56 ,  A61Q19/00 ,  Y10S977/727 ,  Y10S977/728 ,  Y10S977/729 ,  Y10S977/775 ,  Y10S977/795 ,  Y10S977/896 ,  Y10S977/906 ,  Y10S977/915

Abstract: The invention concerns delivery particles (DP's) for active principles (AP's) based on linear amphiphilic polyamino-acids (PAA's), with &agr;-peptide chains, capable of being spontaneously formed by contacting PAA's with a liquid medium, preferably with water, wherein the hydrophile part of the PAA's is solubilized more than the hydrophobic parts of said PAA's, such that the latter precipitate while being organised in discrete supra-molecular arrangements, of average size ranging between 0.01 and 20 &mgr;m, capable of combining with at least an AP and releasing the latter in vivo, in prolonged and controlled manner. The inventive suspension is characterised in that the recurrent amino acids (rAA's) constituting the main chain of PAA's are identical to or different from one another and are glutamic acid and/or aspartic acid and/or their salts; and some of said rAA's bear at least one hydrophobic group, said hydrophobic group, being identical to or different from one another. The invention is useful as carriers for active principles, in particular pharmaceutical, insulin or for therapeutic uses.

Abstract translation: 本发明涉及基于具有α-肽链的线性两亲性多氨基酸（PAA）的活性成分（AP）的递送颗粒（DP），其能够通过使PAA与液体介质优选与水接触而自发形成，其中 PAA的亲水部分比所述PAA的疏水部分溶解得多，使得后者沉淀，同时以分散的分子结构组织，平均尺寸范围为0.01至20μm，能够与至少一种AP和 以延长和受控的方式在体内释放后者。 本发明的悬浮液的特征在于，构成PAA主链的复发氨基酸（rAA）彼此相同或不同，为谷氨酸和/或天冬氨酸和/或其盐; 并且一些所述rAA携带至少一个疏水基团，所述疏水基团彼此相同或不同。 本发明可用作活性成分的载体，特别是药物，胰岛素或用于治疗用途。

公开(公告)号：US08101209B2

公开(公告)日：2012-01-24

申请号：US10826690

申请日：2004-04-19

Applicant: Valérie Legrand ,  Catherine Castan ,  Rémi Meyrueix ,  Gérard Soula

Inventor： Valérie Legrand ,  Catherine Castan ,  Rémi Meyrueix ,  Gérard Soula

IPC: A61K9/16 ,  A61K9/50

CPC classification number: A61K9/5078 ,  A61K9/5015 ,  A61K9/5026 ,  Y10S514/951 ,  Y10S514/963 ,  Y10S514/965

Abstract: 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 comprises 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.

Abstract translation: 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，其活性成分体系中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“。 该系统包括微胶囊（200至600μm），其包含涂覆有包含亲水性聚合物A（Eudragit L）和疏水化合物B（植物蜡，熔点= 40）的膜（最大40重量％））的AP芯 -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：US07879362B2

公开(公告)日：2011-02-01

申请号：US11723553

申请日：2007-03-21

Applicant: Catherine Castan ,  Valerie Legrand ,  Rémi Meyrueix ,  Gérard Soula

Inventor： Catherine Castan ,  Valerie Legrand ,  Rémi Meyrueix ,  Gérard Soula

IPC: A61K9/16

CPC classification number: A61K9/5073 ,  A61K9/2081 ,  A61K9/4858 ,  A61K9/4866

Abstract: The invention concerns a galenic system with prolonged/controlled release of the medicinal and/or nutritional active principle, for oral administration. The aim is to provide a system enabling to obtain with one single tolerable and acceptable dose of active principle, efficient therapeutic protection over 24 hours (increasing the bioabsorption time without affecting bioavailability). To achieve this, the invention provides a composition comprising two controlled release systems associated in series, namely: individualised coated particles (microcapsules) of active principle forming an internal phase, the coating comprising a film-forming polymer P1 (ethylcellulose), a nitrogenous polymer (polyvinylpyrrolidone), a softener (castor oil) and a lubricant (magnesium stearate), and an external phase of functional carriers: polyelectrolytic hydrophilic polymer: (alginate), neutral hydrophilic polymer (hydroxypropylmethylcellulose) and a gelling additive (calcium acetate), said composition spontaneously forming in the presence of water, a cohesive and stable composite macroscopic solid, wherein the external continuous phase is a gelled matrix including the active principle microcapsules. The invention is useful for delayed oral galenic formulation of metformin.

Abstract translation: 本发明涉及用于口服给药的药物和/或营养活性成分的延长/受控释放的盖仑系统。 目的是提供一种能够以一个单一可耐受和可接受剂量的活性成分获得的系统，24小时以上的有效治疗保护（增加生物吸收时间而不影响生物利用度）。 为了实现这一点，本发明提供了一种组合物，其包含两个串联的控制释放系统，即：形成内相的活性成分的单独的涂覆颗粒（微胶囊），该涂层包含成膜聚合物P1（乙基纤维素），含氮聚合物 （聚乙烯吡咯烷酮），软化剂（蓖麻油）和润滑剂（硬脂酸镁）和功能性载体的外相：聚电解亲水性聚合物：（藻酸盐），中性亲水性聚合物（羟丙基甲基纤维素）和胶凝添加剂（乙酸钙），所述 在水的存在下自发形成的组合物，粘性和稳定的复合宏观固体，其中外部连续相是包含活性成分微胶囊的凝胶基质。 本发明可用于二甲双胍延迟口服盖仑制剂。