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    Colloidal suspension of submicronic particles for carrying active principles and their mode of preparation
    1.
    发明申请
    Colloidal suspension of submicronic particles for carrying active principles and their mode of preparation 审中-公开
    用于携带活性成分的亚微粒子的胶体悬浮液及其制备方式

    公开(公告)号：US20080015332A1

    公开(公告)日：2008-01-17

    申请号：US11878364

    申请日：2007-07-24

    申请人： Nathan Bryson ,  Gerard Soula

    发明人： Nathan Bryson ,  Gerard Soula

    IPC分类号： C08G69/08

    CPC分类号： A61Q19/00 ,  A61K8/11 ,  A61K9/5138 ,  A61K9/5146 ,  A61K2800/413 ,  B01J13/0021

    摘要： The invention concerns a suspension of biocompatible particles for carrying active principles. Said carrier particles are based on a double-block hydrophilic neutral polyaminoacid/hydrophobic neutral polyaminoacid copolymer. Said hydrophilic neutral polyaminoacid/hydrophobic neutral polyaminoacid particles are capable of combining in colloidal suspension in non-dissolved state, at least an active principle and of releasing same, in particular in vivo, in prolonged and/or delayed delivery. The invention also concerns a powdery solid from which are derived the carrier particles and the preparation of said solid and of said suspension of active principle based on hydrophilic neutral polyaminoacids/hydrophobic neutral polyaminoacids. Said carrier particles form spontaneously and in the absence of surfactants or organic solvents, stable aqueous suspensions. The invention also concerns the carrier particles in dry form, the method for preparing them, and pharmaceutical compositions (in dry form or suspension) comprising said carrier particles associated with an active principle.

    摘要翻译： 本发明涉及用于携带活性成分的生物相容性颗粒的悬浮液。 所述载体颗粒基于双嵌段亲水性中性聚氨基酸/疏水性中性聚氨基酸共聚物。 所述亲水性中性聚氨基酸/疏水性中性聚氨基酸颗粒能够在非溶解状态的胶体悬浮液，至少一种活性成分和在其延长和/或延迟递送中特别是在体内释放它们的胶态混合物中结合。 本发明还涉及一种粉末状固体，其衍生为载体颗粒，以及基于亲水性中性聚氨基酸/疏水性中性聚氨基酸的所述固体和所述活性成分悬浮液的制备。 所述载体颗粒自发形成，并且在不存在表面活性剂或有机溶剂的情况下形成稳定的水悬浮液。 本发明还涉及干燥形式的载体颗粒，其制备方法和包含与活性成分相关联的所述载体颗粒的药物组合物（干燥形式或悬浮液）。

    Colloidal suspension of submicronic particles for delivering active principles and method for preparing same
    2.
    发明申请
    Colloidal suspension of submicronic particles for delivering active principles and method for preparing same 审中-公开
    用于递送活性成分的亚微粒子的胶体悬浮液及其制备方法

    公开(公告)号：US20070190162A1

    公开(公告)日：2007-08-16

    申请号：US11583941

    申请日：2006-10-20

    申请人： Sylvain Caillol ,  Remi Meyruiex ,  Nathan Bryson ,  Alain Soum ,  Gerard Soula ,  Anne-Francoise Mingotaud

    发明人： Sylvain Caillol ,  Remi Meyruiex ,  Nathan Bryson ,  Alain Soum ,  Gerard Soula ,  Anne-Francoise Mingotaud

    IPC分类号： A61K9/14

    CPC分类号： A61K8/88 ,  A61K8/0241 ,  A61K9/5153 ,  A61K9/5192 ,  A61K2800/413 ,  A61K2800/56 ,  A61Q19/00 ,  B82Y5/00 ,  C08G81/00 ,  C08J3/14 ,  C08J2377/12

    摘要： The present invention is directed to a suspension of particles for delivering active principles, in particular proteins. Said particles are based on a diblock copolymer consisting of a neutral hydrophobic alpha hydroxy carboxylic acid polymer block and a hydrophilic linear polyaminoacid block with peptide alpha chaining, at least partly ionized. Said alpha hydroxy carboxylic acid polymer/linear polyaminoacid delivery particles spontaneously obtainable in the absence of surfactant can be stable. Said delivery particles are capable of being associated undissolved in colloidal suspension with at least an active principle and of delayed or prolonged release thereof. The invention is also directed to a powdery solid from which are derived the delivery particles and the preparation of said solid and said delivery particle suspension.

    摘要翻译： 本发明涉及用于递送活性成分的颗粒的悬浮液，特别是蛋白质。 所述颗粒基于由中性疏水性α羟基羧酸聚合物嵌段和具有至少部分电离的肽α链的亲水性线性聚氨基酸嵌段组成的二嵌段共聚物。 在不存在表面活性剂的情况下自发获得的所述α羟基羧酸聚合物/线性聚氨基酸输送颗粒可以是稳定的。 所述递送颗粒能够以至少一种活性成分和延迟或延长释放的胶体悬浮液的形式相互不溶解。 本发明还涉及粉末状固体，其衍生自所述输送颗粒以及所述固体和所述输送颗粒悬浮液的制备。

    Colloidal formulation of long-acting insulin and its preparation
    6.
    发明申请
    Colloidal formulation of long-acting insulin and its preparation 审中-公开
    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。

    Colloidal suspension of submicronic particles for carrying active principles and their mode of preparation
    7.
    发明授权
    Colloidal suspension of submicronic particles for carrying active principles and their mode of preparation 失效
    用于携带活性成分的亚微粒子的胶体悬浮液及其制备方式

    公开(公告)号：US07270832B2

    公开(公告)日：2007-09-18

    申请号：US10398134

    申请日：2001-10-05

    申请人： Nathan Bryson ,  Gérard Soula

    发明人： Nathan Bryson ,  Gérard Soula

    IPC分类号： A61K9/10

    CPC分类号： A61Q19/00 ,  A61K8/11 ,  A61K9/5138 ,  A61K9/5146 ,  A61K2800/413 ,  B01J13/0021

    摘要： A suspension of biocompatible particles based on a double-block hydrophilic neutral polyminoacid/hydrophobic neutral polyaminoacid copolymer and suitable for carrying active principles. The carrier particles can combine in colloidal suspension in a non-dissolved state with an active principle and release same, particularly in vivo, in prolonged and/or delayed delivery. The carrier particles may be derived from a powdery solid, and spontaneously form stable aqueous suspensions in the absence of surfactants or organic solvents. The invention also concerns the carrier particles in dry form, the method of preparing them, and pharmaceutical compositions (in dry form or suspension) which include the carrier particles associated with an active principle.

    摘要翻译： 基于双嵌段亲水性中性聚氨基酸/疏水性中性聚氨基酸共聚物的生物相容性颗粒的悬浮液，适用于携带活性成分。 载体颗粒可以以非溶解状态的胶态悬浮液与活性成分结合，并在延长和/或延迟递送中特别在体内释放它们。 载体颗粒可以衍生自粉末状固体，并且在没有表面活性剂或有机溶剂的情况下自发形成稳定的水性悬浮液。 本发明还涉及干燥形式的载体颗粒，其制备方法和包括与活性成分相关的载体颗粒的药物组合物（干燥形式或悬浮液）。

    Colloidal suspension of submicronic particles as vectors for active principles and method for preparing same
    8.
    发明授权
    Colloidal suspension of submicronic particles as vectors for active principles and method for preparing same 失效
    亚微粒子作为活性成分载体的胶态悬浮液及其制备方法

    公开(公告)号：US07226618B1

    公开(公告)日：2007-06-05

    申请号：US10130783

    申请日：2000-10-11

    申请人： Franck Touraud ,  Nathan Bryson

    发明人： Franck Touraud ,  Nathan Bryson

    IPC分类号： A61K9/14 ,  A61K9/16 ,  A61K9/20 ,  A61K9/22 ,  A61K9/48

    CPC分类号： A61K8/044 ,  A61K8/90 ,  A61K9/5138 ,  A61K2800/413 ,  A61Q19/00 ,  B01J13/0021 ,  B82Y5/00

    摘要： A suspension of vector particles (PV) based on polyamino acids and have a mean hydrodynamic diameter between 30 and 120 nm, and an insulin load factor of from 5 to 25% of associated insulin volume relative to the polyamino acid volume forming the vector particles. The polyamino acids are double-block polymers containing hydrophilic and hydrophobic monomers. The suspension may be prepared by copolymerizing N-carboxy anhydrides of hydrophobic monomers and precursors of hydrophilic monomers, in the presence of N-methyl pyrrolidone and methanol. The copolymer is optionally neutralized, subjected to dialysis, concentrated and water is eliminated to produce a solid powder, which can be suspended in a liquid to produce the colloidal suspension. Active principles such as insulin or vaccines are associated with the carrier particles to prepare special pharmaceutical products.

    摘要翻译： 基于聚氨基酸的载体颗粒（PV）的悬浮液并且具有30至120nm的平均流体动力学直径和相对于形成载体颗粒的聚氨基酸体积的相关胰岛素体积的5至25％的胰岛素负载因子。 聚氨基酸是含有亲水和疏水单体的双嵌段聚合物。 悬浮液可以通过在N-甲基吡咯烷酮和甲醇的存在下共聚疏水单体的N-羧酸酐和亲水单体的前体来制备。 共聚物任选被中和，进行透析，浓缩并除去水，以产生固体粉末，其可以悬浮在液体中以产生胶体悬浮液。 活性成分如胰岛素或疫苗与载体颗粒相关，以制备特殊的药物产品。

    Colloidal suspension of nanoparticles based on an amphiphilic copolymer
    9.
    发明授权
    Colloidal suspension of nanoparticles based on an amphiphilic copolymer 失效
    基于两亲性共聚物的纳米粒子的胶体悬浮液

    公开(公告)号：US07709445B2

    公开(公告)日：2010-05-04

    申请号：US10473821

    申请日：2002-03-26

    申请人： Gérard Soula ,  Nathan Bryson

    发明人： Gérard Soula ,  Nathan Bryson

    IPC分类号： A61K38/02 ,  A61K9/10

    CPC分类号： A61K9/5146 ,  A61K9/1075 ,  Y10S514/937 ,  Y10S514/941

    摘要： 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.

    摘要翻译： 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。

    Collagen peptides modified by grafting mercapto functions, method for the production thereof and uses thereof as biomaterials
    10.
    发明授权
    Collagen peptides modified by grafting mercapto functions, method for the production thereof and uses thereof as biomaterials 失效
    通过接枝巯基功能修饰的胶原肽，其制备方法及其用途作为生物材料

    公开(公告)号：US06916909B1

    公开(公告)日：2005-07-12

    申请号：US09914426

    申请日：2000-03-01

    申请人： Florence Nicolas ,  Nathan Bryson

    发明人： Florence Nicolas ,  Nathan Bryson

    IPC分类号： A61L15/00 ,  A61L15/32 ,  A61L17/00 ,  A61L17/08 ,  A61L24/00 ,  A61L27/00 ,  A61L27/24 ,  A61L31/00 ,  A61L33/00 ,  C07K1/08 ,  C07K14/78 ,  C08H1/06 ,  C08L89/00 ,  A61K38/17 ,  A61F13/00 ,  C07K1/00

    CPC分类号： A61L27/24 ,  A61L15/325 ,  A61L17/08 ,  C07K14/78

    摘要： The invention relates to novel collagen peptides that are modified by grafting free or substitued thiol functions carried by mercaptoamine radicals. The aim of the invention is to provide thiol collagens that can be cross-linked in a sufficient and controlled manner by forming S—S bridges and which are biocompatible. This is achieved by means of the inventive thiol collagens which are characterized in that the mercaptoamine radicals are identical to or different from each other and are exclusively grafted on the aspartic and glutamic acids of the collagen chain by amide bonds. The invention also relates to a method for the production of said thiol and cross-linkable collagens. The novel modified cross-linkable and/or cross-linked collagens can be used as biomaterials.

    摘要翻译： 本发明涉及通过接枝由巯基胺自由基携带的游离或取代的硫醇官能团来修饰的新型胶原肽。 本发明的目的是提供可以通过形成S-S桥并以生物相容性的方式以充分和受控的方式交联的硫醇胶原蛋白。 这通过本发明的硫醇胶原实现，其特征在于巯基胺基彼此相同或不同，并且通过酰胺键独特地接枝在胶原链的天冬氨酸和谷氨酸上。 本发明还涉及生产所述硫醇和可交联胶原蛋白的方法。 可改性的可交联和/或交联的胶原蛋白可用作生物材料。