公开(公告)号：US06872357B1

公开(公告)日：2005-03-29

申请号：US09721609

申请日：2000-11-22

申请人： Victor Bronshtein ,  Lynn Linkowski

发明人： Victor Bronshtein ,  Lynn Linkowski

IPC分类号： A01N1/02 ,  C12N1/04 ,  B01J19/00 ,  A61L11/00

CPC分类号： A01N1/02 ,  A01N1/0221 ,  C12N1/04

摘要： This invention relates to formulations and methods for preserving sensitive biologicals, viruses, bacteria and eukaryotic cells by drying. More particularly, the invention relates to preservation mixtures containing viruses or cells and protectants, including a combination of a methylated monosaccharide and a disaccharide, or oligosaccharide, wherein the mixtures are adapted to stabilize these during dehydration and subsequent storage at ambient and higher temperature.

摘要翻译： 本发明涉及通过干燥来保存敏感生物，病毒，细菌和真核细胞的制剂和方法。 更具体地说，本发明涉及包含病毒或细胞和保护剂的保存混合物，包括甲基化单糖和二糖或寡糖的组合，其中所述混合物适于在脱水和随后在环境温度和较高温度下储存期间使其稳定。

公开(公告)号：US20100120014A1

公开(公告)日：2010-05-13

申请号：US12462855

申请日：2009-08-10

申请人： Victor Bronshtein

发明人： Victor Bronshtein

IPC分类号： C12N9/96 ,  C12N1/04 ,  C12N5/02 ,  A01N1/00

CPC分类号： A01N1/02 ,  A01N1/0231 ,  A01N1/0284 ,  A61K9/1652 ,  A61K35/18 ,  A61K35/52 ,  C12N1/04 ,  C12N7/00 ,  C12N9/00 ,  C12N11/04 ,  C12N2760/20151

摘要： A method of formulating high ambient temperature (room temperature and above) stable biologics (biologically active macromolecules, enzymes, serums, vaccines, viruses, pesticides, drug delivery systems, liposomes, cells suspensions, sperm, erythrocytes, other blood cells, stem cells, multicellular tissues, skin, heart valves) including secondary drying comprising at least two steps of stability drying at elevated temperature: 35° C., 40° C., 45° C., 50° C., and higher temperatures. The method could be applied to stabilize biologics encapsulated in alginate gel microspheres for better oral delivery. The method encompasses the following: microspheres are formulated using a cryo-encapsulation procedure comprised of mixing drops of frozen preservation mixture (To form the preservation mixture, biologics are mixed with preservation solutions containing sodium alginate.) with frozen drops of a calcium solution (i.e. calcium gluconate) and subsequent warming to form the gel particles.

摘要翻译： 制定高环境温度（室温及以上）稳定生物制剂（生物活性大分子，酶，血清，疫苗，病毒，农药，药物递送系统，脂质体，细胞悬浮液，精子，红细胞，其他血细胞，干细胞， 多细胞组织，皮肤，心脏瓣膜），包括二次干燥，其包括在升高的温度下稳定干燥的至少两个步骤：35℃，40℃，45℃，50℃和更高的温度。 该方法可用于稳定包封在藻酸盐凝胶微球中的生物制剂，以更好地口服。 该方法包括以下：使用包含冷冻保存混合物滴的冷冻包封方法配制微球体（将形成保存混合物的生物制品与含藻酸钠的保存溶液混合）与冷冻的钙溶液滴（即 葡萄糖酸钙）并随后升温以形成凝胶颗粒。

公开(公告)号：US06509146B1

公开(公告)日：2003-01-21

申请号：US08979458

申请日：1997-11-26

申请人： Victor Bronshtein

发明人： Victor Bronshtein

IPC分类号： A01N100

CPC分类号： C12N9/0006 ,  A01N1/02 ,  A01N1/0221 ,  A61K35/18 ,  A61K35/52 ,  B01J13/00 ,  C12N1/04 ,  C12N7/00 ,  C12N9/00 ,  C12N9/96

摘要： This invention discloses methods for the long-term preservation of industrial scale biological solutions and suspensions containing biologically active molecules, cells and small multicellular specimens at ambient temperatures by dehydration in amorphous very viscous liquid or glass state. The scale up method comprises the primary drying step of boiling under vacuum to form a mechanically-stable foam and a secondary drying step to increase the stability. Vitrification can subsequently be achieved by cooling the dried material to the storage temperature which is lower than the glass transition temperature.

摘要翻译： 本发明公开了通过在无定形非常粘稠的液体或玻璃状态下脱水，在环境温度下长期保存含有生物活性分子，细胞和小多细胞标本的工业规模生物溶液和悬浮液的方法。 缩放方法包括在真空下沸腾以形成机械稳定的泡沫的第一干燥步骤和增加稳定性的二次干燥步骤。 随后可以通过将干燥的材料冷却至低于玻璃化转变温度的储存温度来实现玻璃化。

公开(公告)号：US06884866B2

公开(公告)日：2005-04-26

申请号：US10274719

申请日：2002-10-18

申请人： Victor Bronshtein ,  Kevin R. Bracken ,  John G. Cambell

发明人： Victor Bronshtein ,  Kevin R. Bracken ,  John G. Cambell

IPC分类号： F26B5/02 ,  F26B5/04 ,  C08F6/00

CPC分类号： F26B5/04 ,  F26B5/02

摘要： The present invention discloses apparatus and methods of inducing bubble nucleation to overcome problems commonly associated with preservation by foam formation. Specifically, the invention relates to methods of using bubble nucleation in foam formation to preserve sensitive biological materials. Preferred methods of inducing bubble nucleation include, mixing, chamber rotation, crystals, and ultrasound.

摘要翻译： 本发明公开了引发气泡成核的装置和方法，以克服与通过泡沫形成的保存通常相关的问题。 具体地，本发明涉及在泡沫形成中使用气泡成核以保存敏感的生物材料的方法。 引发气泡成核的优选方法包括混合，室旋转，晶体和超声波。

公开(公告)号：US06692695B1

公开(公告)日：2004-02-17

申请号：US09589381

申请日：2000-06-07

申请人： Victor Bronshtein ,  Kevin R. Bracken ,  Ronnie K. Livers ,  David R. Williams

发明人： Victor Bronshtein ,  Kevin R. Bracken ,  Ronnie K. Livers ,  David R. Williams

IPC分类号： B01J1900

CPC分类号： A61K9/122 ,  A61K9/145 ,  A61K9/146 ,  A61K9/1623 ,  A61K9/1629 ,  A61K9/1694 ,  A61K47/26 ,  C12N1/04

摘要： This invention relates to barrier methods for preserving sensitive biological materials as a porous foam, subsequently crushing the foam to form a powder, and optionally formulating mixtures of preserved powdered biological materials. The invention also encompasses an apparatus for integrating the methods of foam formation and subsequent crushing of the preserved biological materials using barrier technology.

摘要翻译： 本发明涉及用于将敏感生物材料保存为多孔泡沫的隔离方法，随后将泡沫破碎以形成粉末，以及任选配制保留的粉末状生物材料的混合物。 本发明还包括一种使用阻挡技术整合泡沫形成方法和随后破碎保存的生物材料的装置。

公开(公告)号：US06306345B1

公开(公告)日：2001-10-23

申请号：US09306137

申请日：1999-05-06

申请人： Victor Bronshtein ,  Kevin R. Bracken ,  Ronnie K. Livers ,  David R. Williams

发明人： Victor Bronshtein ,  Kevin R. Bracken ,  Ronnie K. Livers ,  David R. Williams

IPC分类号： B01J1900

CPC分类号： A61K47/26 ,  A61K9/122 ,  A61K9/145 ,  A61K9/146 ,  A61K9/1623 ,  A61K9/1629 ,  A61K9/1694 ,  C12N1/04 ,  Y10S516/928

摘要： This invention relates to barrier methods for preserving sensitive biological materials as a porous foam, subsequently crushing the foam to form a powder, and optionally formulating mixtures of preserved powdered biological materials. The invention also encompasses an apparatus for integrating the methods of foam formation and subsequent crushing of the preserved biological materials using barrier technology.

摘要翻译： 本发明涉及用于将敏感生物材料保存为多孔泡沫的隔离方法，随后将泡沫破碎以形成粉末，以及任选配制保留的粉末状生物材料的混合物。 本发明还包括一种使用阻挡技术整合泡沫形成方法和随后破碎保存的生物材料的装置。

公开(公告)号：US10272033B2

公开(公告)日：2019-04-30

申请号：US14292809

申请日：2014-05-30

申请人： Victor Bronshtein

发明人： Victor Bronshtein

IPC分类号： A61K35/741 ,  A61K9/00

摘要： Biopharmaceuticals, such as vaccine agents and probiotics, are encapsulated in carbohydrate-glass particles and embedded in an amorphous polymer substrate to produce polymeric compositions containing ambient-temperature stable biopharmaceuticals for syringeless administration to patients such as via dissolvable films, micro-needle patches and similar medical delivery devices. The amorphous polymer substrate is soluble in both water and volatile organic solvents, yet the carbohydrate-glass particles are insoluble in organic solvents. A method for formulation of the polymeric compositions containing ambient-temperature stable biopharmaceuticals includes combining biopharmaceuticals encapsulated in carbohydrate-glass particles with polymer in organic solvent and evaporating the organic solvent to yield a water soluble polymeric composition containing ambient-temperature stable biopharmaceuticals.

公开(公告)号：US09469835B2

公开(公告)日：2016-10-18

申请号：US11569342

申请日：2005-06-01

申请人： Victor Bronshtein

发明人： Victor Bronshtein

IPC分类号： A01N1/02 ,  C12N9/04 ,  C12N9/96 ,  C12N1/04

CPC分类号： C12N1/04 ,  A01N1/0284 ,  C12N9/0006 ,  C12N9/96

摘要： Significant research is being done to develop and improve delivery mechanisms for biopharmaceuticals and vaccines, including pulmonary (inhalation), nasal, transdermal, and oral alternatives. Market projections indicate that the delivery of proteins and vaccines by inhalation and oral formulation has become and will continue to be increasingly important. These delivery mechanisms, to be effective, will require better stabilization of the biologicals so that they can maintain potency and effectiveness at ambient temperatures for extended periods of time. The novel Preservation by Vaporization (PBV) Technology described herein provides cost-effective and efficient industrial scale stabilization of proteins, viruses, bacteria, and other sensitive biologicals, thereby allowing a production of products that are not possible to be produced by existing methods. The suggested new PBV process comprises primary drying under vacuum from a partially frozen state (i.e. slush) at near subzero temperatures followed by stability drying at elevated temperatures (i.e., above 40 degrees Celsius). The new suggested method can be performed aseptically in unit doze format (in vials) and/or in bulk format (in trays, bags, or other containers). The drying can be performed as a continuous load process in a manifold vacuum dryer comprising a plurality (e.g., 30) of vacuum chambers attached to a condenser during the drying.

摘要翻译： 正在进行重大研究，以开发和改进生物制药和疫苗的输送机制，包括肺部（吸入），鼻腔，经皮和口服替代物。 市场预测表明，通过吸入和口服制剂递送蛋白质和疫苗已经并将继续变得越来越重要。 这些传递机制要有效，将需要更好地稳定生物体，使其能够在环境温度下保持长时间的效力和有效性。 本文所述的新型蒸发保存技术（PBV）技术提供了蛋白质，病毒，细菌和其他敏感生物的成本有效和高效的工业规模稳定化，从而允许生产不可能通过现有方法生产的产品。 建议的新的PBV方法包括在几乎零下的温度下从部分冷冻状态（即，冷却）在真空下初次干燥，然后在升高的温度（即高于40摄氏度）下稳定地干燥。 新建议的方法可以在单位打盹格式（小瓶）和/或批量格式（托盘，袋子或其他容器）中无菌地进行。 干燥可以在包括在干燥期间连接到冷凝器的多个（例如，30个）真空室的歧管真空干燥器中作为连续加载过程进行。

公开(公告)号：US06537666B1

公开(公告)日：2003-03-25

申请号：US09694630

申请日：2000-10-23

申请人： Victor Bronshtein

发明人： Victor Bronshtein

IPC分类号： B32B516

CPC分类号： B32B9/02 ,  Y10T428/2984 ,  Y10T428/2991 ,  Y10T428/2998

摘要： The present invention relates to methods of forming a humidity barrier using fats or other materials that can form an amorphous coating for particles comprising sensitive biological materials in a dehydrated and/or a vitrified state. Since the hydrophobic coating may be sticky, a second hard-shell coating is applied to prevent the particles from sticking together. This approach would minimize exposure of the dried biological material to atmospheric moisture and the consequent loss of biological activity.

摘要翻译： 本发明涉及使用脂肪或其它材料形成防潮屏障的方法，该材料可以形成包含处于脱水和/或玻璃化状态的敏感生物材料的颗粒的无定形涂层。 由于疏水涂层可能是粘性的，所以施加第二硬壳涂层以防止颗粒粘在一起。 这种方法将使干燥的生物材料暴露于大气水分并导致生物活性的丧失。

公开(公告)号：US20140356408A1

公开(公告)日：2014-12-04

申请号：US14292809

申请日：2014-05-30

申请人： Victor Bronshtein

发明人： Victor Bronshtein

IPC分类号： A61L26/00 ,  A61K35/74

CPC分类号： A61K9/0021 ,  A61K35/741 ,  Y02A50/387 ,  Y02A50/406 ,  Y02A50/465 ,  Y02A50/471 ,  Y02A50/483

摘要： Biopharmaceuticals, such as vaccine agents and probiotics, are encapsulated in carbohydrate-glass particles and embedded in an amorphous polymer substrate to produce polymeric compositions containing ambient-temperature stable biopharmaceuticals for syringeless administration to patients such as via dissolvable films, micro-needle patches and similar medical delivery devices. The amorphous polymer substrate is soluble in both water and volatile organic solvents, yet the carbohydrate-glass particles are insoluble in organic solvents. A method for formulation of the polymeric compositions containing ambient-temperature stable biopharmaceuticals includes combining biopharmaceuticals encapsulated in carbohydrate-glass particles with polymer in organic solvent and evaporating the organic solvent to yield a water soluble polymeric composition containing ambient-temperature stable biopharmaceuticals.

摘要翻译： 诸如疫苗剂和益生菌之类的生物药物被包封在碳水化合物 - 玻璃颗粒中并且嵌入到无定形聚合物基质中以产生含有环境温度稳定的生物药物的聚合物组合物，用于向患者注射无菌施用，例如通过可溶解的膜，微针贴片和类似物 医疗输送装置 无定形聚合物基材可溶于水和挥发性有机溶剂，但碳水化合物玻璃颗粒不溶于有机溶剂。 制备含有环境温度稳定的生物药物的聚合物组合物的方法包括将包封在碳水化合物玻璃颗粒中的生物药物与聚合物结合在有机溶剂中并蒸发有机溶剂以产生含有环境温度稳定的生物药物的水溶性聚合物组合物。