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1. 发明申请

US20090110742A1 Long-acting colloidal insulin formulation and its preparation 失效
标题翻译：长效胶体胰岛素制剂及其制备
公开(公告)号：US20090110742A1
公开(公告)日：2009-04-30
申请号：US11632992
申请日：2005-06-09
申请人： Alain Constancis , Florence Nicolas , Remi Meyrueix , Olivier Soula
发明人： Alain Constancis , Florence Nicolas , Remi Meyrueix , Olivier Soula
IPC分类号： A61K9/14 , A61K38/28 , A61P3/10
CPC分类号： A61K38/28 , A61K9/1075 , A61K9/5138 , A61K9/5146 , A61K9/5192 , Y10S977/773 , Y10S977/906
摘要： The invention relates to injectable long-acting insulin formulations for the treatment of types I and II diabetes in humans and animals.The essential object of the invention is to provide an injectable long-acting insulin formulation in the form of a colloidal suspension which is stable, which has a good local tolerance and toxicity compatible with the chronic treatment of diabetics, and which maintains a substantial hypoglycemic effect extending over at least 24 hours after a single administration, e.g. by the subcutaneous route.To achieve this object, the invention relates to a stable aqueous colloidal formulation of insulin-laden nanoparticles of at least one poly(Leu-block-Glu) in which the pH is between 5.8 and 7.0, the osmolarity O (in mOsmol) . . . : 270≦O≦800, and the viscosity v (in mPa.s) is low, namely v≦40. The nanoparticles of poly(Leu-block-Glu) have a mean hydrodynamic diameter Dh such that: 15≦Dh≦40.The invention relates to an antidiabetic drug based on this long-acting insulin formulation and injectable using needles of gauge 29G, 30G or 31G.
摘要翻译：本发明涉及用于治疗人和动物中I型和II型糖尿病的可注射长效胰岛素制剂。本发明的基本目的是提供一种稳定的胶体悬浮液形式的可注射的长效胰岛素制剂，其具有与糖尿病患者的慢性治疗相适应的良好的局部耐受性和毒性，并且其保持显着的降血糖效应在单次给药后延长至少24小时，例如通过皮下途径。为了实现这个目的，本发明涉及至少一种pH（在5.8至7.0之间），渗透压浓度O（以mOsmol计）的至少一种聚（Leu-block-Glu）的含胰岛素的纳米颗粒的稳定水性胶体制剂。。。：270 <= 0 <= 800，粘度v（mPa.s）低，即v <= 40。聚（Leu-block-Glu）的纳米颗粒具有平均流体动力学直径Dh，使得：15 <= Dh <= 40。本发明涉及基于该长效胰岛素制剂的抗糖尿病药物，并使用量规29G，30G或31G的针头进行注射。

2. 发明授权

US08017156B2 Long-acting colloidal insulin formulation and its preparation 失效
标题翻译：长效胶体胰岛素制剂及其制备
公开(公告)号：US08017156B2
公开(公告)日：2011-09-13
申请号：US11632992
申请日：2005-06-09
申请人： Alain Constancis , Florence Nicolas , Rémi Meyrueix , Olivier Soula
发明人： Alain Constancis , Florence Nicolas , Rémi Meyrueix , Olivier Soula
IPC分类号： A61K9/14 , A61K38/28
CPC分类号： A61K38/28 , A61K9/1075 , A61K9/5138 , A61K9/5146 , A61K9/5192 , Y10S977/773 , Y10S977/906
摘要： The invention relates to injectable long-acting insulin formulations for the treatment of types I and II diabetes in humans and animals.The essential object of the invention is to provide an injectable long-acting insulin formulation in the form of a colloidal suspension which is stable, which has a good local tolerance and toxicity compatible with the chronic treatment of diabetics, and which maintains a substantial hypoglycemic effect extending over at least 24 hours after a single administration, e.g. by the subcutaneous route.To achieve this object, the invention relates to a stable aqueous colloidal formulation of insulin-laden nanoparticles of at least one poly(Leu-block-Glu) in which the pH is between 5.8 and 7.0, the osmolarity O (in mOsmol) . . . : 270≦O≦800, and the viscosity v (in mPa·s) is low, namely v≦40. The nanoparticles of poly(Leu-block-Glu) have a mean hydrodynamic diameter Dh such that: 15≦Dh≦40.The invention relates to an antidiabetic drug based on this long-acting insulin formulation and injectable using needles of gauge 29 G, 30 G or 31 G.
摘要翻译：本发明涉及用于治疗人和动物中I型和II型糖尿病的可注射长效胰岛素制剂。本发明的基本目的是提供一种稳定的胶体悬浮液形式的可注射的长效胰岛素制剂，其具有与糖尿病患者的慢性治疗相适应的良好的局部耐受性和毒性，并且其保持显着的降血糖效应在单次给药后延长至少24小时，例如通过皮下途径。为了实现这个目的，本发明涉及至少一种pH（在5.8至7.0之间），渗透压浓度O（以mOsmol计）的至少一种聚（Leu-block-Glu）的含胰岛素的纳米颗粒的稳定水性胶体制剂。。。：270＆nlE; O＆nlE; 800，粘度v（mPa·s）低，即v＆nlE; 40。聚（Leu-block-Glu）的纳米颗粒具有平均流体动力学直径Dh，使得：15＆nlE; Dh＆nlE; 40。本发明涉及一种基于该长效胰岛素制剂的抗糖尿病药物，并使用量规29 G，30 G或31 G的针头进行注射。

3. 发明授权

US06790438B1 Cross-linked collagenic peptide for preventing post-surgical adhesions 失效
标题翻译：交联胶原肽用于预防手术后粘连
公开(公告)号：US06790438B1
公开(公告)日：2004-09-14
申请号：US09914424
申请日：2002-01-14
申请人： Alain Constancis , Remi Meyrueix
发明人： Alain Constancis , Remi Meyrueix
IPC分类号： A61L3106
CPC分类号： A61L31/044 , A61L31/045 , Y10S128/08
摘要： The aim of the invention is to provide a modified collagen peptide for preventing post-operative adhesions that is non-toxic, economic, in addition to being easy to obtain, sterilize, manipulate and implement, having controlled biodegradability and presenting a sufficiently strong initial mechanical resistance in situ (cohesion). This is achieved in the case of the modified collagen peptide for preventing post-operative adhesions according to the invention which is characterized in that it comprises at least one collagen peptide that is modified by grafting thiol functions that are free or substituted, cross-linkable and/or at least partly cross-linked, whereby the thiol functions are provided by mercaptoamine radicals that are exclusively grafted on the aspartic and glutamic acids of the collagen chains by means of amide bonds. The modified collagen peptide can exist in the form of a homogeneous or composite film, as a gel or in as a liquid which can be applied and cross-linked per se as on in vivo tissue.
摘要翻译：本发明的目的是提供一种改进的胶原肽，用于防止术后粘连，除了易于获得，消毒，操作和实施之外，还具有无毒的，经济的，具有受控的生物降解性并具有足够强的初始机械原位抵抗力（内聚力）。在用于预防根据本发明的术后粘连的改性胶原肽的情况下实现，其特征在于其包含至少一种胶原肽，所述胶原肽通过接枝游离或取代，可交联的硫醇官能团和 /或至少部分交联，由此巯基功能由巯基胺基团提供，其通过酰胺键专门接枝在胶原链的天冬氨酸和谷氨酸上。修饰的胶原肽可以以均匀或复合膜的形式存在，如凝胶或以液体形式存在，其本身可作为体内组织施用和交联。

4. 发明申请

US20080175921A1 Colloidal formulation of long-acting insulin and its preparation 审中-公开
标题翻译：长效胰岛素的胶体制剂及其制备
公开(公告)号：US20080175921A1
公开(公告)日：2008-07-24
申请号：US11907039
申请日：2007-10-09
申请人： Alain Constancis , David Duracher , Olivier Soula , Nathan Bryson
发明人： Alain Constancis , David Duracher , Olivier Soula , Nathan Bryson
IPC分类号： A61K38/28 , A61P3/10 , A61K9/107
CPC分类号： A61K38/28 , A61K9/0019 , A61K9/1075 , A61K9/5146 , A61K9/5192 , A61K47/34
摘要： The invention relates to injectable long-acting insulin formulations for the treatment of type I and II diabetes in humans and animals.The main objective of the invention is to provide a long-acting insulin formulation in the form of a colloidal suspension: which allows easy filling of a syringe through a small diameter needle (for example with the gauge 29 G, 30 G or 31 G) and/or which can be easily injected through a small diameter needle (for example with the gauge 29 G, 30 G or 31 G), without damaging the therapeutic efficacy of the insulin. To achieve this objective, the subject of the invention is an aqueous and stable colloidal formulation of nanoparticles of at least one poly(Leu-block-Glu), loaded with insulin, in which the pH is such that: 6.0≦pH≦7.0which comprises at least one magnesium salt in a quantity such that: the osmolarity Osm (in mOsmol) is such that: 270≦Osm≦600, the viscosity v (in mPa·s), measured according to a procedure Mv, is such that: v≦15; the poly(Leu-block-Glu) concentration (in mg/ml) is between 30 and 70, preferably between 38 and 65.
摘要翻译：本发明涉及用于治疗人和动物的I型和II型糖尿病的可注射的长效胰岛素制剂。本发明的主要目的是提供胶体悬浮液形式的长效胰岛素制剂：其允许通过小直径针头（例如用量规29G，30G或31G）容易地填充注射器，和/或其可以容易地通过小直径的针（例如用量规29G，30G或31G）注射，而不损害胰岛素的治疗功效。为了实现这一目的，本发明的主题是含有至少一种负载有胰岛素的聚（Leu-block-Glu）的纳米颗粒的水溶性和稳定的胶体制剂，其中pH值使得：6.0 <= pH = 7.0，其包含至少一种镁盐，其量使得：渗透压浓度Osm（mOsmol）为：270 <= Osm <= 600，根据程序Mv测量的粘度v（mPa.s）是这样的：v <= 15; 聚（Leu-block-Glu）浓度（mg / ml）在30和70之间，优选在38和65之间。

5. 发明授权

US08679540B2 Pharmaceutical formulations for the prolonged release of active principle(s), and their applications, especially therapeutic applications 有权
标题翻译：用于延长释放活性成分的药物制剂及其应用，特别是治疗应用
公开(公告)号：US08679540B2
公开(公告)日：2014-03-25
申请号：US11808456
申请日：2007-06-11
申请人： Cécile Bonnet-Gonnet , David Chognot , Olivier Soula , Alain Constancis
发明人： Cécile Bonnet-Gonnet , David Chognot , Olivier Soula , Alain Constancis
IPC分类号： A61K9/14 , A61K9/50 , A61K39/395 , A61K39/00 , A61K31/00 , A61K38/00
CPC分类号： A61K9/10 , A61K9/1635 , A61K31/70 , A61K31/715 , A61K38/212 , A61K38/27 , A61K38/28 , A61K47/34
摘要： The present invention relates to novel pharmaceutical formulations based on aqueous colloidal suspensions for the prolonged release of one or more active principles, and to the applications, especially therapeutic applications, of these formulations. Formulations may include an aqueous colloidal suspension of low viscosity based on micrometric particles of a water-soluble, biodegradable, amphiphilic polymer carrying hydrophobic groups and ionizable hydrophilic groups that are at least partially ionized, said particles being capable of associating spontaneously and non-covalently with an active principle, at pH=7.0, under isotonic conditions. This suspension contains multivalent ions of opposite polarity to that of the hydrophilic groups, the ratio r, defined by the formula r=n×([IM]/[GI]), where n is the valency of said multivalent ions, [IM] is the molar concentration of multivalent ions, [GI] is the molar concentration of ionizable groups GI, being between 0.3 and 10.
摘要翻译：本发明涉及基于用于延长释放一种或多种活性成分的水性胶体悬浮液以及这些制剂的应用，特别是治疗应用的新型药物制剂。制剂可以包括基于水溶性，可生物降解的两亲性聚合物的微米颗粒的低粘度的水性胶体悬浮液，其携带至少部分电离的疏水基团和可离子化的亲水基团，所述颗粒能够自发地和非共价地缔合，在pH = 7.0时，在等渗条件下的活性成分。该悬浮液含有与亲水基团相反极性的多价离子，由式r = n×（[IM] / [GI]）定义的比率r，其中n是所述多价离子的价态，[IM] 是多价离子的摩尔浓度，[GI]是可离子化基团GI的摩尔浓度，介于0.3和10之间。

6. 发明申请

US20100021549A1 Microparticle oral form useful for the modified release of nanoparticles 审中-公开
标题翻译：用于纳米粒子改性释放的微粒口服形式
公开(公告)号：US20100021549A1
公开(公告)日：2010-01-28
申请号：US12509109
申请日：2009-07-24
申请人： Rémi Meyrueix , Rafael Jorda , Anne-Sophie Daviaud , Alain Constancis
发明人： Rémi Meyrueix , Rafael Jorda , Anne-Sophie Daviaud , Alain Constancis
IPC分类号： A61K9/14 , A61K38/02 , A61K38/28 , A61K8/73 , A61K8/64 , A61K31/715 , A61K31/7088
CPC分类号： A61K9/5078 , A61K8/11 , A61K8/64 , A61K8/731 , A61K8/8135 , A61K8/8147 , A61K8/8152 , A61K38/00 , A61K2800/412 , A61Q19/00
摘要： The present invention aims to propose novel microparticle oral forms for the modified release of active ingredient(s), in particular protein or peptide in nature. It also relates to the uses, in particular therapeutic or cosmetic, of these microparticle oral forms.
摘要翻译：本发明的目的是提出新型的微粒口服形式用于活性成分（特别是蛋白质或肽）的改性释放。它还涉及这些微粒口服形式的用途，特别是治疗或化妆品。

7. 发明授权

US5646239A Organic products containing reactive thiol functions, one method for preparing same, and biomaterials containing said products 失效
标题翻译：含有反应性硫醇功能的有机产物，其制备方法和含有所述产物的生物材料
公开(公告)号：US5646239A
公开(公告)日：1997-07-08
申请号：US578539
申请日：1996-03-06
申请人： Alain Constancis , Gerard Soula
发明人： Alain Constancis , Gerard Soula
IPC分类号： A61L17/00 , A61K9/70 , A61K47/34 , A61L17/10 , A61L27/00 , A61L27/18 , A61L27/26 , C07C323/51 , C07C323/60 , C08G69/42 , C08G75/00 , C08G75/14
CPC分类号： C08G69/42 , A61K47/34 , A61K9/7015 , A61L17/10 , A61L27/18 , A61L27/26
摘要： The present invention relates to novel organic products resulting, for example, from the condensation of a dicarboxylic acid with a sulfur-containing amino acid or one of its derivatives. These products contain reactive thiol SH functions which can be oxidized to form disulfide bridges, resulting in polymers, which may or may not be crosslinked.These novel organic products correspond to the following formula: ##STR1## The invention also relates to the polymers and/or networks deriving from the products of formula (I) and to one of the methods for obtaining these products and their derivatives.Applications as biomaterials: sutures, ligatures, prostheses, adhesives or systems for the controlled release of active principles.
摘要翻译： PCT No.PCT / FR94 / 00914 Sec。 371日期1996年3月6日 102（e）1996年3月6日PCT PCT 1994年7月21日PCT公布。第WO95 / 03272号公报日期1995年2月2日本发明涉及由二羧酸与含硫氨基酸或其衍生物之一缩合得到的新型有机产物。这些产物含有可被氧化形成二硫键的活性硫醇SH官能团，产生聚合物，其可以交联也可以不交联。这些新型有机产物符合下列公式：本发明还涉及衍生自式（I）的产物的聚合物和/或网络以及获得这些产物及其衍生物的方法之一。作为生物材料的应用：用于控制释放活性成分的缝线，结扎线，假体，粘合剂或系统。

8. 发明申请

US20120156257A1 METHOD FOR THE PREPARATION OF NANOPARTICLES 审中-公开
标题翻译：制备纳米颗粒的方法
公开(公告)号：US20120156257A1
公开(公告)日：2012-06-21
申请号：US13329999
申请日：2011-12-19
申请人： Alexandre Drogoz , Alain Constancis
发明人： Alexandre Drogoz , Alain Constancis
IPC分类号： A61K9/00 , B82Y40/00 , B82Y5/00
CPC分类号： A61K9/5146 , A61K9/0019 , A61K9/10 , A61K9/5192 , A61K31/00 , A61K47/645 , A61K47/6935 , B82Y5/00
摘要： The present invention relates to a novel method for the preparation of nanoparticles with a diameter smaller than or equal to 500 nm, comprising bringing a solution (1) comprising nanoparticles of a first polyelectrolyte in the charged state, bearing hydrophobic side groups, together with (2) at least one second polyelectrolyte of opposite polarity to that of the first polyelectrolyte, characterized in that the ratio Z of the number of cationic groups relative to the number of anionic groups in the mixture of the two polyelectrolytes is comprised between 0.1 and 0.75 or between 1.3 and 2; and the total mass concentration C of polyelectrolytes is strictly less than 2 mg/g of the mixture.
摘要翻译：本发明涉及一种制备直径小于或等于500nm的纳米颗粒的新方法，包括将包含第一聚电解质纳米颗粒的带有疏水侧基的纳米颗粒的溶液（1）与（ 2）至少一种与第一聚电解质相反极性的第二聚电解质，其特征在于阳离子基团数目相对于两种聚电解质混合物中的阴离子基团数目的Z的比率为0.1至0.75或在1.3和2之间; 聚电解质的总质量浓度C严格小于2mg / g的混合物。

9. 发明授权

US5496872A Adhesive compositions for surgical use 失效
标题翻译：用于外科用途的粘合剂组合物
公开(公告)号：US5496872A
公开(公告)日：1996-03-05
申请号：US277069
申请日：1994-07-19
申请人： Alain Constancis , Ge/ rard Soula , Jean-Louis Tayot , Je/ ro/ me Tiollier
发明人： Alain Constancis , Ge/ rard Soula , Jean-Louis Tayot , Je/ ro/ me Tiollier
IPC分类号： A61L26/00 , A61K6/00 , A61L24/04 , A61L27/18 , A61L27/26 , A61L31/04 , A61L31/06 , C08G75/14 , C09J159/00 , C09J181/04 , A61K38/00 , A61L25/00 , C08G69/10 , C08L1/00
CPC分类号： A61L31/041 , A61L24/043 , A61L24/046 , A61L27/18 , A61L27/26 , A61L31/06
摘要： The invention relates to an adhesive, biocompatible, biodegradable and non-toxic composition for surgical use, in particular for binding tissues, which composition is of the following general formula: ##STR1## in which: R is a hydrocarbon chain containing from 1 to 50 carbon atoms,R.sub.1 and R.sub.2 are identical or different and are chosen from the following groups: ##STR2## R.sub.3, R.sub.4, R.sub.5, R.sub.6 and R.sub.7 independently represent hydrogen or an aliphatic and/or alicyclic and/or aromatic group, ##STR3##
摘要翻译：本发明涉及用于外科用途，特别是结合组织的粘合剂，生物相容性，可生物降解和无毒组合物，该组合物具有以下通式：含有1至50个碳原子，R 1和R 2相同或不同并且选自以下组： R3，R4，R5，R6和R7独立地表示氢或脂族和/或脂环族和/或芳族基团，

10. 发明申请

US20080102128A1 Modified-release microparticles based on amphiphilic copolymer and on active principles(s) and pharmaceutical formulations comprising them 审中-公开
标题翻译：基于两亲性共聚物的改性释放微粒和包含它们的活性成分和药物制剂
公开(公告)号：US20080102128A1
公开(公告)日：2008-05-01
申请号：US11878947
申请日：2007-07-27
申请人： Alain Constancis , You-Ping Chan
发明人： Alain Constancis , You-Ping Chan
IPC分类号： A61K38/16 , A61K9/14 , A61P43/00 , C08G63/44
CPC分类号： A61K47/42 , A61K9/0019 , A61K9/0075 , A61K9/1658 , A61K9/19 , A61K38/2013 , A61K38/212 , A61K38/27 , A61K38/28
摘要： The present invention relates to novel microparticles formed of amphiphilic polyamino acids which transport active principle(s), AP(s), in particular protein and peptide active principle(s), and to novel modified-release pharmaceutical formulations comprising said AP microparticles. The aim of the invention is to develop novel microparticles, charged with AP, obtained by aggregation of nanoparticles of amphiphilic polyamino acids and having improved properties, in particular in the dry solid form, with regard to their ability to be dispersed and, concerning the reconstituted suspension, its stability and its ability to be easily handled and injected. The invention relates firstly to microparticles of amphiphilic polyamino acid (PO) comprising at least one AP (associated noncovalently) which spontaneously form a colloidal suspension of nanoparticles in water, at pH 7.0, under isotonic conditions; which microparticles a. are obtained by atomization of a solution or colloidal suspension of PO comprising at least one AP, b. have a size of between 0.5 and 100 microns, c. and are dispersible in colloidal suspension. The invention also relates to the process for the preparation of these microparticles, to a liquid formulation comprising a suspension of these PO/AP microparticles, to a reconstitution process and kit for this formulation and to a dry form of this formulation.
摘要翻译：本发明涉及由两亲多聚氨基酸形成的新型微粒，其中所述两亲性聚氨基酸输送活性成分，特别是蛋白质和肽活性成分的AP，以及包含所述AP微粒的新型改性释放药物制剂。本发明的目的是开发新的带有AP的微粒，其通过聚集两亲性聚氨基酸的纳米颗粒而获得，并且具有改进的性质，特别是以干固体形式，关于其分散能力，以及关于重构的悬浮液，其稳定性及其易于处理和注入的能力。本发明首先涉及在等渗条件下包含至少一种AP（非共价相关的）的自亲形成纳米颗粒在水中的胶体悬浮液（pH 7.0）的两亲性聚氨基酸（PO）的微粒; 哪个微粒a。通过雾化包含至少一种AP的PO的溶液或胶态悬浮液获得，b。具有0.5至100微米的尺寸，c。并且可分散在胶体悬浮液中。本发明还涉及制备这些微粒的方法，包括这些PO / AP微粒的悬浮液的液体制剂，用于该制剂的重构方法和试剂盒以及该制剂的干燥形式。

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