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CN1116104C - 可规模化的通过干燥保存生物活性物质的方法 - Google Patents

可规模化的通过干燥保存生物活性物质的方法 Download PDF

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CN1116104C
CN1116104C CN97196422A CN97196422A CN1116104C CN 1116104 C CN1116104 C CN 1116104C CN 97196422 A CN97196422 A CN 97196422A CN 97196422 A CN97196422 A CN 97196422A CN 1116104 C CN1116104 C CN 1116104C
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V·布龙施泰因
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Abstract

一种通过在待脱水流体物质中形成稳定泡沫来保存敏感的生物分散液、悬浮液、乳液和溶液的方法，该方法既有助于干燥流体中一种或多种生物活性底物，又有助于制备易分开的、适用于进一步商业用途的干燥产物。稳定泡沫是这样形成的：对生物液体抽真空，使其在远低于100℃的温度下“沸腾”。换句话说，将减小的压力施用于生物活性物溶液或悬浮液，使溶液或悬浮液在沸腾时起泡，产生稳定的开腔或闭腔泡沫。在沸腾前，生物物质的比活可用常规浓缩技术(如蒸发、冷冻干燥和膜分离技术)来提高。

Description

可规模化的通过干燥保存生物活性物质的方法
                          发明领域
本发明涉及敏感的生物活性溶质(例如酶、蛋白质、病毒、血清、疫苗、脂质体和细胞悬浮液)以及其悬浮液、乳液和分散液的保存方法。
                          发明背景
生物活性物质的长期保存对我们来说是一种独特的挑战，因为生物活性物质是我们这个星球上最脆弱的、最易受环境影响的结构(这是它的本质特点)。当然，也有极少数水合物是稳定的，它们能被分离纯化并储藏在室温溶液中较长时间。
从商业和实践的角度来看，以干形式储藏生物活性物质具有许多优点。成功干燥的试剂、物质和组织的重量减少，保存所需的空间减少，但是它们的保存期限却增加。干物质的室温保存比低温保存方案及其费用更经济。
目前生产干的生物活性物质的方法主要包括冷冻干燥、喷雾干燥(参见美国专利No.5,563,318，该专利涉及喷雾干燥的一种变化方案)和流化床干燥，和对液相的小液滴或薄膜进行简单的蒸发干燥。降温保存方法可能有脱水作用，它包括冷冻干燥和/或深低温冷冻。
在生物活性物质经蜕变(transmute)干燥但仍可恢复生物活性形式的许多过程中，特别存在的问题始终是简单的空气干燥或真空干燥步骤很难放大。干燥是扩散限制型过程，因此对于超过10微升的水分含量来说，水分的除去就变得更加复杂，这是一点；而且待干燥的底物越大，其中心部份的有效干燥就越困难。干燥时间与水的扩散系数成反比，与样品大小的平方成正比。我们总不能老是求助于喷雾干燥技术，因为该技术中的一些具有典型的高温对柔弱的生物活性物质有破坏作用。而且，用已知的干燥方法来制备干燥的物质有时会产生稠密的、难溶的团块，这些团块在大规模(full-scale)商业性生物和药物应用中不能很好地作进一步处理。
因此，需要有一种通过干燥来保存敏感生物活性物质的可放大的方法。
                          发明概述
为了满足这一需求，本发明涉及一种通过从待干燥流体物质形成稳定泡沫来保存敏感的生物悬浮液和溶液的方法，这种方法既有助于流体中一种或多种生物活性底物的干燥，又有助于制得适用于进一步商业用途的易溶的干燥产物。稳定的泡沫是这样形成的：对浓缩的液体抽真空，使其在在远低于100℃的温度下“沸腾”。换句话说，使生物活性物溶液或悬浮液受减压作用，使它们在沸腾过程中产生泡沫，在起泡过程中进一步除去水分，最终产生稳定的开腔或闭腔泡沫。这些泡沫很容易通过切割、研磨或其它分隔方法来细分，而且起泡作用本身通过使液体蒸发面积或其它溶剂放散(evolutin)面积最大化而增强了水分的除去。
本发明的一个较佳实施方案公开了一种通过干燥来保存生物活性物质的方法。方法包括下列步骤：使含有生物活性剂的溶液、分散液或悬浮液受相应于低于24托的压力的真空作用，其中该真空度足以使溶液、分散液或悬浮液沸腾，从而使沸腾的溶液、分散液或悬浮液在沸腾期间干燥产生物理上稳定的泡沫。
在另一较佳实施方案中，所述流体静压在0到7.6托之间。
在另一较佳实施方案中，在使所述溶液、分散液或悬浮液沸腾的步骤之前，通过在压力高于7.6托的真空度下蒸发、从部分冷冻状态蒸发(即冷冻干燥)，或用反向渗透或其它膜技术，以减少溶液、分散液或悬浮液沸腾的时间。
在另一较佳实施方案中，通过在升高温度下对所述稳定泡沫施加真空或干空气中的一种来进行二次干燥。
根据本发明的另一实施方案，通过沸腾产生物理上稳定的泡沫来保存生物活性物质的方法还包括使泡沫与合适溶剂接触保存并使所述稳定泡沫重新水合的步骤。重新水合可在高于重新水合前泡沫保存温度的温度下进行。或者，重新水合前的泡沫保存温度至少和环境温度一样高。或者，重新水合可在等于或低于泡沫保存温度的温度下进行。在另一变化方案中，重新水合前的泡沫保存温度低于或等于环境温度。在另一个形式中，重新水合所用溶剂是包括低温保护剂的水性溶液。
                          发明详述
本发明是一种通过从待干燥流体物质形成稳定泡沫来保存敏感的生物分散液、悬浮液和溶液的方法，这种方法既有助于干燥流体中一种或多种生物活性底物，又有助于制得适用于进一步商业用途的容易细分的干燥产物。稳定的泡沫是这样形成的：进一步对生物液体抽真空，使其在远低于100℃的温度下“沸腾”。换句话说，使生物活性物溶液或悬浮液受减压作用，使溶液或悬浮液在沸腾过程中产生泡沫，产生稳定的开腔或闭腔泡沫。样品中的沸腾在室温或更低温度下进行，以避免生物活性物质受热损伤。如果真空室中的流体静压低于24托(这是25℃水上的平衡蒸汽压)，施加真空使得生物液体在室温(通常为25℃)或更低温度下沸腾。
在沸腾前，生物物质的比活可采用常规浓缩技术(如蒸发、冷冻干燥和膜分离技术)来提高。
在形成泡沫后，可在升高的温度下在真空下对泡沫进行进一步(“第二次”)干燥，干燥时间为达到预定的玻璃转化温度所需的时间。这些泡沫很容易通过切割、研磨或其它分隔方法来细分，而且起泡作用本身通过使液体蒸发面积最大化而增强了水分的除去。(通常，待干燥物质的溶剂部分是水性的；然而，应当理解本发明适用于各种类型的溶液和悬浮液，包括那些含有非水性溶剂或这些溶剂的混合物的溶液和悬浮液)。
适用于该真空-沸腾-泡沫-形成革新方法的生物液体实际上是无限的。确实何溶液或悬浮液均可用本发明的真空沸腾方法来脱水，但是该方法在保存敏感的生物物质方面有明显的优点(即，由于较低的干燥温度而避免了破坏)。对于掺入了保护剂以及基本上任何类型溶剂的溶液，当它受低于大气压作用并在沸腾过程中产生泡沫时，它受的干燥作用会增强。保护剂可以包括(没有限制)：糖(包括蔗糖)、碳水化合物、多糖、水溶性聚合物、肽或蛋白质等，只要保护剂能增强生物活性物质经受干燥和保存的能力，而且不干扰特定的生物活性。
一旦理解了本发明中干燥过程与减压沸腾的结合，就可以看出在最简单的实例中本发明的装置是一种真空泵和温度控制干燥器的新组合装置。这一组合的其它任选特征包括：测定温度和热流控制的传感器，根据从这些及其它传感器收集的数据来计算其它过程参数的微处理器等。这种装置能够实现新的用于干燥的二维的真空和温度的设置方案。
在本发明的一个重要实例中，泡沫的形成包括两个步骤：(a)通过真空下沸腾使含有生物活性剂的溶液或分散液充分脱水，形成稳定的不会被破坏的泡沫，和(b)随后将泡沫二次干燥至泡沫稳定并且不会在保存时被破坏。如果泡沫中物质的玻璃转化温度高于保存温度，泡沫在长期保存期间不会破裂。
如上所述，本发明提供了一种可改变规模的保存敏感的生物活性物质(蛋白质、酶、血清、疫苗、病毒、脂质体和细胞悬浮液)方法，该方法采用了独特的工程化干燥方法。采用这种方法，就可以用水或水性溶液使样品重新水合，以使该过程逆转并恢复成原始的生物活性。该方法适用于保存药物、流体或实际上其它任何生物活性产物或溶质。
在本发明的方法中，相当大量的生物活性液体(溶液或悬浮液)可通过真空下沸腾而脱水形成稳定的泡沫，因为沸腾是湍流的可规模化的过程。泡沫的形成是一个动态的过程，它取决于形成泡沫过程中温度和真空度的改变速度，以及含有生物活性物质的溶液或悬浮液的初始浓度和组成。根据本发明制得的泡沫可整个保存或可细分或研磨，当要使用它们时，为了要重新恢复它们原来的生物活性，泡沫只需进行重新水合。通过加入表面活性剂或其它合成或生物聚合物，可进一步增强泡沫的稳定性，只要那些添加剂不干扰打算转化成干形式的溶质的生物活性。可在升高的温度下对干的泡沫进行二次干燥，随后冷却至低于玻璃转化温度的保存温度，以确保保存时的泡沫稳定性。在恒定的流体静压下，玻璃态只能通过冷却获得，因为它不取决于样品中的扩散速度。单单地干燥不能获得玻璃态，因为它是缓慢的扩散限制过程。
下列实施例用来描述本发明的实施方案，其中样品在沸腾经蒸发浓缩。尽管这些实施例说明敏感的生物物质可通过形成泡沫来保存，但是本文公开的各个实施方案绝不应被理解为局限于下列工作例中描述的具体过程。
                          实施例1
使含有59.4单位活性/毫升的50％异柠檬酸甘油酯脱氢酶水溶液(购自SigmaChemical Co.)在0.1M Tris HCl缓冲液(pH＝7.4)中透析5小时。在透析后，0.1M TrisHCl溶液中异柠檬酸酯脱氢酶的活性为26±1.8单位/毫升。活性随着透析时稀释而引起的酶浓度的降低而降低。
将100微升的混合物放在1.5毫升塑料管中并在室温下干燥进行保存，该混合物含有50微升50％(重量)的蔗糖溶液和50微升在0.1M Tris HCl缓冲液(pH7.4)中的异柠檬酸酯脱氢酶悬浮液。首先，使样品在低真空度(流体静压P＝0.2大气压)下干燥4小时。第二，使样品在高真空度(P＜0.01大气压)下沸腾4小时。在这一步中，试管内形成了稳定的干泡沫。第三，使样品在真空、室温下，在DRIERITE上保存8天。
在保存规定天数后，用500微升水使样品重新水合。含有干泡沫的样品的重新水合是容易的，它可在几秒种内完成。通过在340nm用分光光度计测定还原NADP的能力来测定重建样品的活性。反应混合物包括：2毫升0.1M Tris HCl缓冲液，pH＝7.4；10微升0.5％(重量)NADP+；10微升10mM MnSO4溶液；10微升50mM 1-异柠檬酸酯；以及10微升异柠檬酸酯脱氢酶溶液。活性为2.6±0.2单位/毫升，这意味着在室温下干燥和随后的保存中活性没有损失。
                          实施例2
将100微升的混合物放在1.5毫升塑料管中并在室温下干燥进行保存，该混合物含有50微升50％(重量)的蔗糖溶液和50微升冰晶核细菌悬浮液(由GenencorInternational，Inc.提供)。首先，使样品在低真空度(流体静压P＝0.2大气压)下干燥4小时。第二，使样品在高真空度(P＜0.01大气压)下沸腾4小时。在真空下沸腾后，试管内形成了稳定的干泡沫。第三，使样品在真空、室温下在DRIERITE上保存8天。在保存8天后，用500微升水使样品重新水合。含有干泡沫的样品的重新水合是容易的，它可在几秒钟内完成。然后测定样品的冰成核活性与对照样品比较。我们发现用本发明方法保存的样品每1000个细菌的冰成核活性与对照样品没有显著区别。
尽管本发明已参照上述特定实施例和细节进行了描述，但是本发明的范围只能取决于在附加的权利要求中所提出的陈述。

Claims (14)

1.一种通过干燥来保存生物活性物质的方法，方法包括下列步骤：使含有生物活性剂的溶液、分散液或悬浮液受相应于低于24托的压力的真空作用，该真空度足以使所述溶液、分散液或悬浮液引起沸腾，从而使得所述沸腾的溶液、分散液或悬浮液在沸腾期间干燥产生物理上稳定的泡沫。
2.根据权利要求1所述的方法，其中所述流体静压在0到7.6托之间。
3.根据权利要求1所述的方法，其中在使所述溶液、分散液或悬浮液沸腾的步骤之前，通过在压力高于7.6托的真空度下蒸发、从部分冷冻状态蒸发即冷冻干燥，或用反向渗透或其它膜技术，以减少溶液、分散液或悬浮液沸腾的时间。
4.根据权利要求1所述的方法，其中通过在升高温度下对所述稳定泡沫施加真空或干空气中的一种来进行二次干燥。
5.根据权利要求4所述的方法，其中在二次干燥步骤后将样品冷却到温度低于干泡沫的玻璃化温度。
6.根据权利要求5所述的方法，其中在施加所述高真空度之前先在所述溶液、分散液或悬浮液中加入表面活性剂，使在二次干燥时增加泡沫稳定性。
7.根据权利要求6所述的方法，其中所述溶液、分散液或悬浮液含有选自糖、碳水化合物、多糖、聚合物、肽、蛋白质及其混合物的保护剂，其中所述保护剂增强了生物活性物质经受干燥和保存的能力。
8.根据权利要求1所述的方法，其中所述方法还包括通过所述泡沫与合适溶剂接触来使所述稳定泡沫重新水合。
9.根据权利要求8所述的方法，其中所述重新水合是在高于重新水合前泡沫保存温度的温度下进行。
10.根据权利要求9所述的方法，其中重新水合前的泡沫保存温度至少和环境温度一样高。
11.根据权利要求8所述的方法，其中所述重新水合在等于或低于重新水合前泡沫保存温度的温度下进行。
12.根据权利要求8所述的方法，其中重新水合前的泡沫保存温度低于或等于环境温度。
13.根据权利要求8所述的方法，其中所述溶剂是包括低温保护剂的水性溶液。
14.根据权利要求7所述的方法，其中所述糖是蔗糖。
CN97196422A 1996-07-15 1997-07-14 可规模化的通过干燥保存生物活性物质的方法 Expired - Fee Related CN1116104C (zh)

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Families Citing this family (97)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2179831T3 (es) * 1992-09-29 2003-02-01 Inhale Therapeutic Syst Liberacion en los pulmones de fragmentos activos de hormona paratiroidiana.
US20030113273A1 (en) * 1996-06-17 2003-06-19 Patton John S. Methods and compositions for pulmonary delivery of insulin
WO1995024183A1 (en) 1994-03-07 1995-09-14 Inhale Therapeutic Systems Methods and compositions for pulmonary delivery of insulin
US6290991B1 (en) 1994-12-02 2001-09-18 Quandrant Holdings Cambridge Limited Solid dose delivery vehicle and methods of making same
EP0782398A1 (en) 1994-09-22 1997-07-09 Quadrant Holdings Cambridge Limited Compositions for use in rehydration and nutrition during athletic exercise and methods of making same
US6964771B1 (en) * 1995-06-07 2005-11-15 Elan Drug Delivery Limited Method for stably incorporating substances within dry, foamed glass matrices
US6509146B1 (en) 1996-05-29 2003-01-21 Universal Preservation Technologies, Inc. Scalable long-term shelf preservation of sensitive biological solutions and suspensions
US6468782B1 (en) * 1996-12-05 2002-10-22 Quadrant Healthcare (Uk) Limited Methods of preserving prokaryotic cells and compositions obtained thereby
GB9705588D0 (en) 1997-03-18 1997-05-07 Anglia Research Foundation Stable particle in liquid formulations
US8563522B2 (en) * 1997-07-08 2013-10-22 The Iams Company Method of maintaining and/or attenuating a decline in quality of life
US20060116330A1 (en) * 1997-07-08 2006-06-01 The Iams Company Methods of mimicking the metabolic effects of caloric restriction by administration of mannoheptulose
US20020035071A1 (en) * 1997-07-08 2002-03-21 Josef Pitha Mimicking the metabolic effects of caloric restriction by administration of glucose antimetabolites
US6309623B1 (en) 1997-09-29 2001-10-30 Inhale Therapeutic Systems, Inc. Stabilized preparations for use in metered dose inhalers
US6565885B1 (en) 1997-09-29 2003-05-20 Inhale Therapeutic Systems, Inc. Methods of spray drying pharmaceutical compositions
US20060165606A1 (en) 1997-09-29 2006-07-27 Nektar Therapeutics Pulmonary delivery particles comprising water insoluble or crystalline active agents
EP1032647B1 (en) * 1997-11-26 2006-03-29 Universal Preservation Technologies, Inc. Preservation of sensitive biological samples by vitrification
US6306345B1 (en) 1998-05-06 2001-10-23 Universal Preservation Technologies, Inc. Industrial scale barrier technology for preservation of sensitive biological materials at ambient temperatures
US6214054B1 (en) 1998-09-21 2001-04-10 Edwards Lifesciences Corporation Method for fixation of biological tissues having mitigated propensity for post-implantation calcification and thrombosis and bioprosthetic devices prepared thereby
JP2002534654A (ja) 1999-01-05 2002-10-15 ユニバーサル プリザーベーション テクノロジーズ インコーポレイテッド 発泡乾燥装置用の真空制御システム
AP1521A (en) * 1999-05-04 2005-12-22 Anhydro Ltd Method for the preservation of viruses and mycoplasma.
US6692695B1 (en) 1999-05-06 2004-02-17 Quadrant Drug Delivery Limited Industrial scale barrier technology for preservation of sensitive biological materials
EP1402003A4 (en) * 1999-08-19 2004-07-14 Universal Preservation Technologies Inc Preservation of bacterial cells below room temperature
AU2046101A (en) * 1999-11-22 2001-06-04 Universal Preservation Technologies, Inc. Preservation and formulation of bioactive materials for storage and delivery in hydrophobic carriers
US7871598B1 (en) 2000-05-10 2011-01-18 Novartis Ag Stable metal ion-lipid powdered pharmaceutical compositions for drug delivery and methods of use
US8404217B2 (en) 2000-05-10 2013-03-26 Novartis Ag Formulation for pulmonary administration of antifungal agents, and associated methods of manufacture and use
TWI290473B (en) 2000-05-10 2007-12-01 Alliance Pharma Phospholipid-based powders for drug delivery
AU2000264912A1 (en) 2000-06-07 2001-12-17 Universal Preservation Technologies, Inc. Industrial scale barrier technology for preservation of sensitive biological materials
MXPA02012583A (es) 2000-06-27 2003-04-10 Hoffmann La Roche Metodo para preparacion de una composicion.
US6537666B1 (en) * 2000-10-23 2003-03-25 Universal Preservation Technologies, Inc. Methods of forming a humidity barrier for the ambient temperature preservation of sensitive biologicals
US7153472B1 (en) * 2000-11-22 2006-12-26 Quadrant Drug Delivery Limited Preservation and formulation of bioactive materials for storage and delivery in hydrophobic carriers
US6872357B1 (en) * 2000-11-22 2005-03-29 Quadrant Drug Delivery Limited Formulation of preservation mixtures containing sensitive biologicals to be stabilized for ambient temperature storage by drying
WO2002090513A2 (en) * 2001-05-07 2002-11-14 Universal Preservation Technologies, Inc. Preservation of competent cells at ambient temperatures
US6884866B2 (en) * 2001-10-19 2005-04-26 Avant Immunotherapeutics, Inc. Bulk drying and the effects of inducing bubble nucleation
WO2003053411A1 (en) 2001-12-19 2003-07-03 Nektar Therapeutics Pulmonary delivery of aminoglycosides
US6878168B2 (en) 2002-01-03 2005-04-12 Edwards Lifesciences Corporation Treatment of bioprosthetic tissues to mitigate post implantation calcification
CA2482448C (en) 2002-04-11 2014-07-08 Medimmune Vaccines, Inc. Preservation of bioactive materials by freeze dried foam
AU2003278166B2 (en) 2002-11-01 2009-01-29 Glaxosmithkline Biologicals S.A. Immunogenic composition
US20050100559A1 (en) * 2003-11-07 2005-05-12 The Procter & Gamble Company Stabilized compositions comprising a probiotic
US20050100636A1 (en) * 2003-11-10 2005-05-12 Megan Botteri [A Low-Calorie Sports Drink For Physically Active Women That is Fortified with Iron, Calcium and Essential Vitamins for Use in Rehydration and Replacing Electrolytes Lost During Periods of Physical Activity]
US7785635B1 (en) 2003-12-19 2010-08-31 The Procter & Gamble Company Methods of use of probiotic lactobacilli for companion animals
US8894991B2 (en) * 2003-12-19 2014-11-25 The Iams Company Canine probiotic Lactobacilli
US8877178B2 (en) * 2003-12-19 2014-11-04 The Iams Company Methods of use of probiotic bifidobacteria for companion animals
US20050158294A1 (en) * 2003-12-19 2005-07-21 The Procter & Gamble Company Canine probiotic Bifidobacteria pseudolongum
US20050152884A1 (en) 2003-12-19 2005-07-14 The Procter & Gamble Company Canine probiotic Bifidobacteria globosum
US9744227B2 (en) 2004-06-02 2017-08-29 Universal Stabilization Technologies, Inc. Compositions containing ambient-temperature stable, inactivated but therapeutically active biopharmaceuticals and methods for formulation thereof
WO2005117962A1 (en) 2004-06-02 2005-12-15 Victor Bronshtein Preservation by vaporization
JP2007277094A (ja) * 2004-06-29 2007-10-25 Chemo Sero Therapeut Res Inst 改変ダニ主要アレルゲン含有医薬組成物
WO2006010273A1 (en) * 2004-07-30 2006-02-02 The University Of British Columbia Method for producing hydrocolloid foams
AU2006253007B2 (en) * 2005-05-31 2012-12-20 Alimentary Health Ltd Feline probiotic Bifidobacteria
CA2609617C (en) * 2005-05-31 2014-07-08 The Iams Company Feline probiotic lactobacilli
JP5214464B2 (ja) 2005-12-28 2013-06-19 アドバンスド バイオニュートリション コーポレーション 多糖類、糖類およびポリオール類の乾燥マトリックスを含む、ガラス形態の、プロバイオティクス細菌用送達媒体およびその製造方法
US8968721B2 (en) 2005-12-28 2015-03-03 Advanced Bionutrition Corporation Delivery vehicle for probiotic bacteria comprising a dry matrix of polysaccharides, saccharides and polyols in a glass form and methods of making same
US9453675B2 (en) * 2006-02-10 2016-09-27 Sp Industries, Inc. Method of inducing nucleation of a material
CN101626682B (zh) 2006-10-27 2014-04-16 爱德华兹生命科学公司 用于外科植入的生物组织
WO2008076975A1 (en) 2006-12-18 2008-06-26 Advanced Bionutrition Corporation A dry food product containing live probiotic
RU2436581C2 (ru) 2007-02-01 2011-12-20 Дзе Иамс Компани Способ уменьшения воспаления и снижения стресса у млекопитающего
JP5307801B2 (ja) * 2007-05-18 2013-10-02 メディミューン・エルエルシー 凍結乾燥フォームによる生物活性材料の防腐
US9101691B2 (en) * 2007-06-11 2015-08-11 Edwards Lifesciences Corporation Methods for pre-stressing and capping bioprosthetic tissue
MX2010001054A (es) 2007-07-26 2010-04-21 Sanofi Pasteur Ltd Composiciones adyuvantes antigenicas y metodos.
US8718113B2 (en) * 2007-09-13 2014-05-06 Enwave Corporation Apparatus and method for dehydrating biological materials
US8357387B2 (en) 2007-12-21 2013-01-22 Edwards Lifesciences Corporation Capping bioprosthetic tissue to reduce calcification
US9771199B2 (en) 2008-07-07 2017-09-26 Mars, Incorporated Probiotic supplement, process for making, and packaging
CN102149813B (zh) * 2008-09-12 2015-05-27 能波公司 利用冷冻和微波使生物材料脱水的设备和方法
EP2410996B1 (en) 2009-03-27 2017-08-02 Advanced Bionutrition Corp. Microparticulated vaccines for the oral or nasal vaccination and boostering of animals including fish
MY157343A (en) 2009-05-26 2016-05-31 Advanced Bionutrition Corp Stable dry powder composition comprising biologically active microorganisms and/or bioactive materials and methods of making
US10104903B2 (en) 2009-07-31 2018-10-23 Mars, Incorporated Animal food and its appearance
WO2011032108A2 (en) * 2009-09-13 2011-03-17 Vu Truong-Le Formulation for room temperature stabilization of a live attenuated bacterial vaccine
US9504750B2 (en) 2010-01-28 2016-11-29 Advanced Bionutrition Corporation Stabilizing composition for biological materials
BR112012018839B1 (pt) 2010-01-28 2020-04-14 Advanced Bionutrition Corp composição vítrea seca compreendendo um material bioativo
EP2549957B1 (en) 2010-03-23 2019-01-30 Edwards Lifesciences Corporation Methods of conditioning sheet bioprosthetic tissue
EP2582411B1 (en) 2010-06-17 2019-05-01 Edwards Lifesciences Corporation Methods for stabilizing a bioprosthetic tissue by chemical modification of antigenic carbohydrates
US8906601B2 (en) 2010-06-17 2014-12-09 Edwardss Lifesciences Corporation Methods for stabilizing a bioprosthetic tissue by chemical modification of antigenic carbohydrates
PL2603100T3 (pl) * 2010-08-13 2019-06-28 Advanced Bionutrition Corp. Kompozycja stabilizująca przechowywanie na sucho materiałów biologicznych
US9351829B2 (en) 2010-11-17 2016-05-31 Edwards Lifesciences Corporation Double cross-linkage process to enhance post-implantation bioprosthetic tissue durability
US10238771B2 (en) 2012-11-08 2019-03-26 Edwards Lifesciences Corporation Methods for treating bioprosthetic tissue using a nucleophile/electrophile in a catalytic system
EP3003246B1 (en) 2013-05-31 2020-11-18 Victor Bronshtein Polymeric compositions containing ambient-temperature stable biopharmaceuticals & methods for formulation thereof
US9615922B2 (en) 2013-09-30 2017-04-11 Edwards Lifesciences Corporation Method and apparatus for preparing a contoured biological tissue
US10959839B2 (en) 2013-10-08 2021-03-30 Edwards Lifesciences Corporation Method for directing cellular migration patterns on a biological tissue
EP3314007B1 (en) 2015-06-25 2024-01-24 Native Microbials, Inc. Methods, apparatuses, and systems for analyzing microorganism strains from complex heterogeneous communities, predicting and identifying functional relationships and interactions thereof, and selecting and synthesizing microbial ensembles based thereon
US9938558B2 (en) 2015-06-25 2018-04-10 Ascus Biosciences, Inc. Methods, apparatuses, and systems for analyzing microorganism strains from complex heterogeneous communities, predicting and identifying functional relationships and interactions thereof, and selecting and synthesizing microbial ensembles based thereon
US10851399B2 (en) 2015-06-25 2020-12-01 Native Microbials, Inc. Methods, apparatuses, and systems for microorganism strain analysis of complex heterogeneous communities, predicting and identifying functional relationships and interactions thereof, and selecting and synthesizing microbial ensembles based thereon
MY194231A (en) 2015-07-29 2022-11-23 Advanced Bionutrition Corp Stable dry probiotic compositions for special dietary uses
CN109874294B (zh) 2016-04-15 2023-06-20 原生微生物股份有限公司 通过施用微生物聚生体或其纯化菌株来提高禽类的农业生产的方法
CN106434840B (zh) * 2016-12-02 2019-08-09 北京中检葆泰生物技术有限公司 一种用于微生物法定量检测维生素b12的微孔板、其试剂盒及其制备方法
US11891647B2 (en) 2016-12-28 2024-02-06 Native Microbials, Inc. Methods, apparatuses, and systems for analyzing complete microorganism strains in complex heterogeneous communities, determining functional relationships and interactions thereof, and identifying and synthesizing bioreactive modificators based thereon
EP3562955A4 (en) 2016-12-28 2020-08-12 Ascus Biosciences, Inc. METHODS, APPARATUS AND SYSTEMS FOR THE ANALYSIS OF STRAINS OF MICRO-ORGANISMS OF HETEROGENEOUS COMMUNITIES COMPLEX WITH TRACEOR ANALYZES, DETERMINATION OF THEIR INTERACTIONS AND FUNCTIONAL RELATIONSHIPS, AND SUMMARY OF MICROBIAL SETS OF MICROBIAL SETS AND MICROBIAL SETS INCLUDING MICROBIAL SETS AND INGREDIENTS
CN106676161B (zh) * 2017-01-03 2020-01-21 北京中检葆泰生物技术有限公司 一种用于微生物法定量检测烟酸的微孔板、其试剂盒及其制备方法
CN106701887B (zh) * 2017-01-03 2020-01-17 北京中检葆泰生物技术有限公司 一种用于微生物法定量检测叶酸的微孔板、其试剂盒及其制备方法
CN106591415B (zh) * 2017-01-03 2019-12-10 北京中检葆泰生物技术有限公司 一种用于微生物法定量检测生物素的微孔板、其试剂盒及其制备方法
CN106676160B (zh) * 2017-01-03 2020-02-21 北京中检葆泰生物技术有限公司 一种用于微生物法定量检测泛酸的微孔板、其试剂盒及其制备方法
US10617756B2 (en) 2017-01-05 2020-04-14 Shimojani, LLC Drug regimen for treatment of cerebral ischemia
WO2018201154A1 (en) * 2017-04-28 2018-11-01 Universal Stabilization Technologies, Inc. Antigenic thermostable polio vaccines & related methods
WO2018222434A1 (en) 2017-05-31 2018-12-06 Edwards Lifesciences Corporation Collagen fibers and articles formed therefrom
US11825862B2 (en) 2017-10-18 2023-11-28 Native Microbials, Inc. Fowl production by administration of a synthetic bioensemble of microbes or purified strains thereof
AU2019212059A1 (en) 2018-01-23 2020-05-21 Edwards Lifesciences Corporation Method for pre-stretching implantable biocompatible materials, and materials and devices produced thereby
JP7138336B2 (ja) * 2018-06-29 2022-09-16 国立大学法人九州工業大学 生体由来の水溶性高分子乾燥品の製造方法及びその製造装置
WO2020092205A1 (en) 2018-11-01 2020-05-07 Edwards Lifesciences Corporation Transcatheter pulmonic regenerative valve

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5271881A (en) * 1987-09-28 1993-12-21 Redding Bruce K Apparatus and method for making microcapsules
US5409703A (en) * 1993-06-24 1995-04-25 Carrington Laboratories, Inc. Dried hydrogel from hydrophilic-hygroscopic polymer

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4642903A (en) * 1985-03-26 1987-02-17 R. P. Scherer Corporation Freeze-dried foam dosage form
JPH0779694B2 (ja) * 1985-07-09 1995-08-30 カドラント バイオリソ−シズ リミテツド 蛋白質および同類品の保護
GB8903593D0 (en) * 1989-02-16 1989-04-05 Pafra Ltd Storage of materials
US5200399A (en) * 1990-09-14 1993-04-06 Boyce Thompson Institute For Plant Research, Inc. Method of protecting biological materials from destructive reactions in the dry state
AU659645B2 (en) * 1991-06-26 1995-05-25 Inhale Therapeutic Systems Storage of materials
US5565318A (en) * 1994-09-02 1996-10-15 Pharmacia Biotech, Inc. Room temperature stable reagent semi-spheres
DK0831790T3 (da) * 1995-06-07 2003-09-01 Elan Drug Delivery Ltd Fremgangsmåder til stabil inkorporering af stoffer i tørre opskummede glasmatricer og derved opnåede sammensætninger

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5271881A (en) * 1987-09-28 1993-12-21 Redding Bruce K Apparatus and method for making microcapsules
US5409703A (en) * 1993-06-24 1995-04-25 Carrington Laboratories, Inc. Dried hydrogel from hydrophilic-hygroscopic polymer

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