CN1798603B - 含有表面改性无机纳米粒子的稳定粒子分散体 - Google Patents
含有表面改性无机纳米粒子的稳定粒子分散体 Download PDFInfo
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- CN1798603B CN1798603B CN2004800150639A CN200480015063A CN1798603B CN 1798603 B CN1798603 B CN 1798603B CN 2004800150639 A CN2004800150639 A CN 2004800150639A CN 200480015063 A CN200480015063 A CN 200480015063A CN 1798603 B CN1798603 B CN 1798603B
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- dispersion
- continuous phase
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- medicament
- silane
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- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K23/00—Use of substances as emulsifying, wetting, dispersing, or foam-producing agents
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- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K23/00—Use of substances as emulsifying, wetting, dispersing, or foam-producing agents
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- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/24—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
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Abstract
本发明涉及粒子的液体分散体，其含表面改性的无机纳米粒子。
Description
发明背景
本发明涉及粒子在液体中的分散体。
常规分散体由两相组成：分散相和连续相。最常见的分散体由单一分散粒子和液态连续相组成。若形成的分散体不稳定，那么分散粒子就会絮结或凝聚，导致两相分离。通常，分散剂用来抑止两相分离。分散剂被吸收到分散粒子表面上以后，分散剂通过空间或静电方式稳定分散体。连续相粘性的增加也可防止分散体的完全相分离。
发明概要
一方面，本发明提供一种包含分散相和连续相的分散体。分散相包含分散在连续相中的粒子。连续相包含液态连续相和表面改性的无机纳米粒子。
另一方面，本发明提供一种稳定分散体的方法，包括加入有效量的相容性表面改性无机纳米粒子至包括含粒子分散相和含液态连续相的分散体中。
另一方面，本发明提供一种药学上的分散体，其中分散相包含一种或多种药剂。
另一方面，本发明提供一种治疗哺乳动物的方法，包括对哺乳动物给用药学有效量的药物分散体，给药方式包括口服法、注射法、经鼻法、吸入法、局部给药或其组合。
另一方面，本发明提供一种包含待分散在连续相中的分散相组分和表面改性无机纳米粒子的分散体试剂盒。
详细说明
本发明的分散体是稳定的分散体，其在使用期内基本上不需要搅动可保持分散态，或通过小的能量输入便易于再分散。通过将有效量的表面改性无机纳米粒子复合到连续相中，赋予包括不溶性粒子和连续相的分散体稳定性。表面改性纳米粒子的“有效量”指这样的量，该量可最小化分散粒子的凝聚，并形成在使用期内基本上不用搅动便可保持分散或用小的能量输入便易于再分散的稳定分散体。不希望受任何理论限制，可以认为纳米粒子是空间上抑止分散相的凝聚，而不是通过电荷抑止。表面改性纳米粒子稳定分散体不使用常规性分散剂。本发明的分散体可含有少于0.001％的表面活性剂、表面活性试剂、洗涤剂和/或那些用在所属领域中的常规分散剂。
本发明所用的“分散体”指分布或悬浮于液态连续相中的固体粒子，所述液态连续相在使用期如数分钟、数小时、数天等内不分离。
本发明中所用的“分离”指液态分散体中的固体粒子逐渐沉淀或成乳状物，形成具有截然不同固体粒子浓度的不同层和连续液相。
本发明中的“分散稳定性”是对分散体趋于分离倾向的描述。对于具有良好分散稳定性的分散体，粒子在连续相中保持基本均匀的分布。对于分散稳定性能差的分散体，粒子在连续相中则不会保持基本均匀的分布，且会分离。
本发明中的“赋形剂”泛指任何惰性添加剂，而不是用于改进气溶胶分散体配方某些性能的主要活性药剂部分。
本发明中的稳定性分散体包括表面改性无机纳米粒子.该表面改性纳米粒子优选分散在整个连续相中的单个未缔合(即不凝聚)的纳米粒子，且优选纳米粒子之间或纳米粒子与分散粒子之间没有不可逆的缔合.术语“缔合”或“与...缔合”包括如共价键、氢键、静电引力、色散力和憎水作用.
选择表面改性纳米粒子，使得由其形成的组合物絮结或凝聚的程度不会影响组合物所希望的性能。选择的表面改性纳米粒子与液态连续相相容。
评估表面改性纳米粒子与液态连续相相容性的方法包括确定得到的组合物是否分离。对于透明的液态连续相，评估表面改性纳米粒子与透明的液态连续相相容性的一种有用方法包括结合表面改性纳米粒子和液相连续相，并观察表面改性纳米粒子是否完全分散到液态连续相中。由于纳米粒子的尺寸比可见光的波长小，所以完全分散时会产生透明的分散体。
由于所选表面改性纳米粒子的无机组分不溶于液态连续相，因此表面改性纳米粒子将分散于但不溶在该相中。粒子的表面改性会使该粒子和液相相容，从而其可完全分散。当纳米粒子尺寸比可见光的波长小时，完全分散时纳米粒子看起来形成透明溶液。随着表面改性纳米粒子尺寸的增加，连续相的模糊程度通常增加。选择希望的表面改性纳米粒子，使得它们不从连续相中沉积出来。
评价表面改性纳米粒子与连续相相容性的再一个步骤包括后来引入分散在连续相中的液体时，组合物在使用期内是否形成稳定的分散相。使用期可能是数分钟、数小时、数天、数周或数年，这取决于它们的用途。例如，当本发明的分散体是色料时，希望分散体保持稳定数月。但是，如果本发明的分散体是配方中的药剂，那么仅需在数分钟内保持稳定即可，直到用药。
也可根据表面基团和连续相的溶解性参数选择合适的表面基团。优选表面基团或衍生表面基团的试剂具有与连续相溶解性参数相似的溶解性参数。例如，当连续相憎水时，本领域的技术人员能从各种憎水性表面基团中进行选择，以获得能与憎水性连续相相容的表面改性粒子。相似地，当连续相亲水时，本领域的技术人员可从各种亲水性表面基中进行选择，当连续相是氢氟烃时，本领域的技术人员可从多种相容性表面基团中进行选择。纳米粒子也可包含至少两种不同的表面基团，它们结合以使纳米粒子具有与连续相溶解性参数类似的溶解性参数。表面改性纳米粒子不是两亲性的。
所选择的表面基团可提供一种统计学平均的随机表面改性的粒子。
表面基团在粒子表面上存在的量足以提供随后分散于连续相而不凝聚的表面改性纳米粒子。优选表面基团存在的量足以在纳米粒子的表面上形成单层、优选连续的单层。
表面改性基团可从表面改性试剂得到。示意性地，表面改性试剂可用通式A-B表示，其中A基团能够连接于粒子表面，B基团是与连续相的组分反应或不反应的相容性基团。选择相容性基团以赋予粒子相对更多极性、相对更少极性或相对非极性。
表面改性剂的适当种类包括如硅烷、有机酸、有机碱和醇、及其组合物。
特别有用的表面改性剂包括硅烷.有用硅烷的例子包括有机硅烷，包括例如，烷基氯硅烷；烷氧基硅烷，例如，甲基三甲氧基硅烷、甲基三乙氧基硅烷、乙基三甲氧基硅烷、乙基三乙氧基硅烷、正丙基三甲氧基硅烷、正丙基三乙氧基硅烷、异丙基三甲氧基硅烷、异丙基三乙氧基硅烷、丁基三甲氧基硅烷、丁基三乙氧基硅烷、己基三甲氧基硅烷、辛基三甲氧基硅烷、3-巯基丙基三甲氧基硅烷、正辛基三乙氧基硅烷、苯基三乙氧基硅烷、聚三乙氧基硅烷、乙烯基三甲氧基硅烷、乙烯基二甲基乙氧基硅烷、乙烯基甲基二乙酰氧基硅烷、乙烯基甲基二乙氧基硅烷、乙烯基三乙酰氧基硅烷、乙烯基三乙氧基硅烷、乙烯基三异丙氧基硅烷、乙烯基三甲氧基硅烷、乙烯基三苯氧基硅烷、乙烯基三(叔-丁氧基)硅烷、乙烯基三(异丁氧基)硅烷、乙烯基三(异丙烯氧基)硅烷和乙烯基三(2-甲氧基乙氧基)硅烷；三烷氧基芳基硅烷；异辛基三甲氧基硅烷；N-(3-三乙氧基甲硅烷基丙基)甲氧基乙氧基乙氧基乙基氨基甲酸酯；N-(3-三乙氧基甲硅烷基丙基)甲氧基乙氧基乙氧基乙基氨基甲酸酯；硅烷功能性(甲基)丙烯酸脂，包括例如：3-(甲基丙烯酰氧基)丙基三甲氧基硅烷、3-丙烯酰氧基丙基三甲氧基硅烷、3-(甲基丙烯酰氧基)丙基三乙氧基硅烷、3-(甲基丙烯酰氧基)丙基甲基二甲氧基硅烷、3-(丙烯酰氧基)甲基二甲氧基硅烷、3-(甲基丙烯酰氧基)丙基二甲基乙氧基硅烷、3-(甲基丙烯酰氧基)甲基三乙氧基硅烷、3-(甲基丙烯酰氧基)甲基三甲氧基硅烷、3-(甲基丙烯酰氧基)丙基二甲基乙氧基硅烷、3-(甲基丙烯酰氧基)丙烯基三甲氧基硅烷和3-(甲基丙烯酰氧基)丙基三甲氧基硅烷；聚二烷基硅氧烷，包括例如聚二甲基硅氧烷；芳基硅烷，包括例如取代和未取代的芳基硅烷；烷基硅烷，包括例如取代和未取代的烷基硅烷，包括例如甲氧基和羟基取代的烷基硅烷，和它们的组合.
美国专利号4,491,508、4,455,205、4,478,876、4,486,504和5,258,225中公开了使用硅烷功能性(甲基)丙烯酸脂进行二氧化硅表面改性的方法。
有用的有机酸表面改性剂包括例如碳的含氧酸(如碳酸)、硫的含氧酸、磷的含氧酸以及它们的组合物。
具有羧酸作用的极性表面改性剂的代表性例子包括CH3O(CH2CH2O)2CH2COOH(在下文用MEEAA表示)和通式为CH3OCH2CH2OCH2COOH的2-(2-甲氧基乙氧基)乙酸(下文用MEAA表示)和以酸或盐形式存在的琥珀酸单(聚乙二醇)酯。
具有羧酸作用的非极性表面改性剂的代表性例子包括辛酸、十二烷酸和油酸。
含磷的酸合适例子包括磷酸，包括例如辛基磷酸、月硅基磷酸、癸基磷酸、十二烷基磷酸、十八烷基磷酸和以酸或盐形式存在的磷酸单(聚乙二醇)酯。
有用的有机碱性表面改性剂包括例如烷基胺，如辛胺、癸胺、十二烷基胺、十八烷基胺和单聚乙二醇胺。
其它有用的非硅烷表面改性试剂的例子包括丙烯酸、甲基丙烯酸、丙烯酸β-羧基乙酯、琥珀酸单-2-(甲基丙烯酰氧基乙酯)及它们的组合物。能赋予纳米粒子极性和活性的有用表面改性剂是琥珀酸单(甲基丙烯酰氧基聚乙二醇酯)。
合适表面改性醇类的例子有脂肪醇，包括例如十八烷基醇、月桂醇、十二烷基醇和糠基醇；脂环族醇，包括例如环己醇；芳香族醇，包括例如苯酚和苯甲基醇；和其组合物。
当连续相包括含芳环的环氧树脂时，有用的表面改性基团可包括芳环。美国专利号5,648,407中公开了适用于环氧树脂组合物的表面改性基团的例子。
多种方法可用来改性纳米粒子的表面，包括例如，加入表面改性剂至纳米粒子(例如，粉末状或胶状的分散体)，并使表面改性剂与纳米粒子反应。本领域技术人员能够理解，多个合成步骤可将纳米粒子和相容性基团结合在一起，并且这在可预见的范围内，例如，反应基团/连接剂可与纳米粒子反应，随后与相容性基团反应。可替换地，反应基团/连接剂可与相容性基团反应，随后与纳米粒子反应。其它有用的表面改进方法公开于例如美国专利号2,801,185和4,522,958中。
纳米粒子是无机物。无机纳米粒子的合适例子包括二氧化硅和金属氧化物纳米粒子，包括氧化锆、二氧化钛和磷酸钙，例如，羟基磷灰石、二氧化铈、氧化铝、氧化铁、氧化矾、氧化锑、氧化锡、氧化铝/二氧化硅，以及它们的组合物，也包括组合材料，例如材料或包围无机芯材料层的混合物。纳米粒子的平均粒径小于约100纳米，在其它实施方式中，不大于约50纳米；约3纳米～约50纳米；约3纳米～约20纳米；以及约5纳米～约10纳米。粒径范围包括在3纳米～小于100纳米间的任何尺寸或范围。若纳米粒子凝聚，则凝聚粒子最大截面的尺寸在任何这些优选的范围内。
有用的表面改性氧化锆纳米粒子包括吸附于粒子表面上的油酸和丙烯酸的组合物。
有用的表面改性二氧化硅纳米粒子包括用硅烷表面改性剂表面改性剂的二氧化硅纳米粒子，包括例如丙烯酰氧基丙基三甲氧基硅烷、3-甲基丙烯酰氧基丙基三甲氧基硅烷、3-巯基丙基三甲氧基硅烷、正辛基三甲氧基硅烷、异辛基三甲氧基硅烷，以及它们的组合物。二氧化硅纳米粒子可用多种表面改性剂处理，包括例如醇，有机硅烷，包括例如烷基三氯硅烷、三烷氧基芳基硅烷、三烷氧基(芳基)硅烷，和它们的组合物，以及有机钛酸盐和它们的混合物。
纳米粒子可以胶状分散体形式存在。市场上可得到的有用未改性二氧化硅起始材料包括产品标号为NALCO 1040、1050、1060、2326、2327的纳米尺寸胶状二氧化硅和购买自Nalco Chemial Co.，Naperville，IL的2329胶状二氧化硅。
有用的金属氧化物胶状分散体包括胶状氧化锆，其合适的例子公开于美国专利号5,037,579中；胶状氧化钛，其有用的例子公开于PCT公开号WO 00/06495中，标题为“Nanosize Metal Oxide Particles forProducing Transparent Metal Oxide Colloids and Ceramers，”(Arney etal.)，于1998年7月30日提交。
本发明的稳定分散体包括液态连续相。连续相可由一种或多种易混或易溶的非反应性组分组成，只要分散粒子可分散在根据连续相组分所用比例得到的液态连续相中即可。
液态连续相的例子包括水，有机液体，例如酸、醇、酮、醛、胺、酰胺、酯、二醇、醚、烃、卤代烃、单体、低聚物、润滑油、植物油(包括单、双和三-甘油酯)、硅油、增湿油(如矿物油和加州希蒙得木油)、燃料油、燃料(包括煤油、汽油、柴油)、乙二醇的低聚物、烷基和芳基硝基化合物、部分或全部氟化的化合物、和聚合物、以及它们的组合物。在某些情况下，液态连续分散体可为至少95、90、85、80、75、70、65、60、55、50、45、40、35、30、25、20、15、10、5wt％的水，且可为介于100～0wt.％间任何范围的水。一些实施方式中，液态连续分散体可为至少95、90、85、80、75、70、65、60、55、50、45、40、35、30、25、20、15、10、5wt％的有机物，且可为介于100～0wt.％间任何范围的有机物。
连续相可含溶解在其中且不影响分散体稳定性的其它成分(有助或阻碍分散的不溶性粒子的分散)，例如，产生生理适应性的赋形剂、盐或有机材料、或分散体的其它有益性质。
分散相可以是任何在液态连续相中具有最小溶解性的粒子。希望粒子的最大直径小于约100微米。分散粒子可以是无机物、有机物或它们的组合物。分散粒子的例子包括药剂、碳黑、二氧化钛、脱落剂、化妆品、颜料和研磨剂。
具体药剂包括抗过敏药、止痛剂、气管扩张剂、抗组胺剂、治疗性蛋白和缩氨酸、止咳药、心绞痛制剂、抗生素、消炎制剂、利尿剂、荷尔蒙、或磺胺类药物，例如引起血管收缩的胺、酶、生物碱或类固醇，以及药剂这些具体例子的组合物，所述可使用的药剂是异丙基肾上腺素、苯肾上腺素、苯丙醇胺、胰高血糖素、肾上腺素红、胰岛素、肾上腺素、麻黄素、那可汀、可待因、阿托品、肝磷脂、吗啡、二氢吗啡酮、二氢吗啡、麦角胺、东莨菪碱、噻吡二胺、氰钴胺、特步他林、利米特罗、舒喘宁、异丙肾上腺素、非诺特罗、oxitropiumbromide、瑞普特罗、布地奈德、氟尼缩松、环索奈德、福莫特罗、丙酸氟替卡松、沙美特罗、丙卡特罗、ipratropiurn、去炎松丙酮化合物、替泼尼旦、莫米松呋喃羧酸酯、秋水仙碱、吡布特罗、氯地米松、氯地米松二丙酸盐、奥西那林、芬太奴、海洛因和dilitiazem。其它的是抗生素，例如新霉素、头孢菌素、链霉素、青霉素、普鲁卡因青霉素、四环素、氯四环素和羟基四环素；促肾上腺皮质荷尔蒙和肾上腺皮质荷尔蒙，例如可的松、氢化可的松、氢化可的松醋酸盐和脱氢皮质(甾)醇；抗过敏化合物如色甘酸钠、奈多罗米蛋白质；和缩氨酸分子如胰岛素、五脒、降血钙素、阿米洛利、干扰素、LHRH类似物、IDNA酶、肝磷脂等。如果可适用，上述所列举的药剂可以用作本领域公知的游离碱或作为一种或多种盐。疫苗也可从该方法受益。
上述所列举的药剂可以用作本领域公知的游离碱或作为一种或多种盐。游离碱或盐的选择将受到配方中药剂物理稳定性的影响。例如，已表明本发明制剂中舒喘宁游离碱比舒喘宁硫酸盐具有更高的分散稳定性。
上述药剂的如下盐类是可以使用的：醋酸盐、苯磺酸盐、安息香酸盐、碳酸氢盐、酒石酸氢盐、溴化物、乙二胺四乙酸钙、右旋樟脑磺酸、碳酸盐、氯化物、柠檬酸盐、二氢氯化物、乙二胺四乙酸盐、乙二磺酸盐、丙酸酯十二烷基硫酸盐、乙磺酸盐、延胡索酸盐、fluceptate、葡萄糖酸盐、谷氨酸盐、甘苯砷酸盐、hexylresorcinate、氢溴酸盐、盐酸盐、羟基萘甲酸盐、碘化物、羟乙磺酸盐、乳酸盐、乳二糖酸盐、苹果酸盐、马来酸盐、扁桃酸盐、甲磺酸盐、甲基溴化物、甲基硝酸盐、甲基磺酸盐、粘多糖盐、乙-苯磺酸盐、硝酸盐、双羟萘酸盐(embonate)、泛酸盐、磷酸盐二磷酸盐、多半乳糖醛酸酯、水杨酸盐、硬脂酸盐、碱式乙酸盐、琥珀酸盐、硫酸盐、丹宁酸盐、酒石酸盐和三乙基碘。
阳离子盐也可使用。合适的阳离子盐包括碱金属盐，例如钠盐、钾盐、铵盐和本领域已知的药学可接受的铵盐和胺的盐，例如氨基乙酸、亚乙基二胺、胆碱、二乙醇胺、三乙醇胺、十八烷基胺、二乙胺、三乙胺、1-氨基-2-丙醇基-氨基-2-(羟基甲基)丙烷-1，3-二醇和1-(3，4-二羟基苯基)-2-异丙基氨基乙醇。
对于药用目的，药剂粉末的粒度应希望不大于100微米直径。在另一个实施方式中，其粒度不应小于25微米直径。从生理学因素考虑，需要的微细固体粉末的粒度在直径上应小于约25微米，且优选小于约10微米。
本发明的医剂分散体含以治疗有效量分散在分散体中的药剂。“治疗有效量”是指其量足以产生治疗效果，例如气管扩张或抗滤过性病原体作用。其量根据本领域技术人员公知的因素而变化，例如具体药剂的药理学行为、治疗条件、服药次数、治疗场所以及其它任何共同给药的治疗剂或赋形剂的存在。药剂浓度取决与所需剂量，但通常为0.01～15wt％、0.01～10wt％、0.01～5wt％、0.01～4wt％、0.01～3wt％或0.01～2wt％，可以使用0.001～15wt％范围内的任何量或范围。
可通过如下给药方式对患者(哺乳动物)用药本发明的医用分散体，用药方式包括口服、注射(如IV、IP、IM、subQ)、局部给药、经鼻法、吸入法以及上述方法的组合.本领域技术人员公知的给药设备均可用来对药用分散体给药.这类设备包括喷雾泵、喷雾器、注射器等.
本发明的分散体试剂盒包括表面改性的无机纳米粒子和分散相组分。该试剂盒的目的在于能够使分散体的终端用户在其所希望的时候通过加入连续相而形成分散体。该试剂盒可包含预定量的分散相组分和将与合适量连续相混合的表面改性纳米粒子。分散相组分和纳米粒子可以粉末/粒子形式提供，或预分散于液态介质中。该试剂盒中的纳米粒子和分散相组分可以混在一起提供或分开单独提供。该试剂盒也可包括对终端用户的使用说明，例如用量、配比、有用的连续相、混合步骤等，以形成本发明的分散体。
本发明的分散体和分散体试剂盒也可包含表面改性的有机分子、未改性的有机分子和/或与表面改性的无机纳米粒子结合在一起的有机聚合纳米粒子。表面改性有机分子、未改性的有机分子和有机聚合微球公开于2003年5月30日提交的美国申请号10/499,677中。
现通过以下实施例对本发明做更详细的阐述。
实施例
异辛基表面改性二氧化硅纳米粒子(IO-纳米SiO2)的制备
根据美国专利公开号2002/0128336中的公开制备异辛基硅烷表面改性二氧化硅纳米粒子(IO-纳米SiO2)。
实施例1-6
通过组合单独装于螺帽瓶中的各种0.1克不溶性固体和1.9克甲苯中的2％IO-纳米SiO2来制备碳黑、氧化铝和氧化铈不溶性粒子的分散体(见美国专利公开号2002/0128336的实施例2)。其它的样品由0.25克固体和1.9克甲苯中2％IO-纳米SiO2制备。然后盖上小瓶，并用手剧烈振荡15秒。将小瓶静放5分钟，然后得到固体的悬浮液。若固体保持悬浮5分钟，那么认为该悬浮液是稳定的。数据见表1。
对比例A-C
精确按照与实施例1、例3、例5相同的方式分别配制对比例A-C(碳黑、氧化铝和氧化铈)，不同的是此处制剂中省略了表面改性的二氧化硅粒子。所有对比悬浮液都不稳定；不溶性固体在低于5分钟内从液相析出。
表1
| 实施例 | 悬浮固体 | 悬浮固体的重量 | 悬浮液是否稳定 |
| 1 | 碳黑 | 0.1克 | 是 |
| 2 | 碳黑 | 0.25克 | 是 |
| 3 | 氧化铝 | 0.1克 | 是 |
| 4 | 氧化铝 | 0.25克 | 是 |
| 实施例 | 悬浮固体 | 悬浮固体的重量 | 悬浮液是否稳定 |
| 5 | 氧化铈 | 0.1克 | 是 |
| 6 | 氧化铈 | 0.25克 | 是 |
例7-15
组合物I
混合250克Nalco 2326(胶状二氧化硅分散体，来自NalcoChemicals，Naperville，IL)、46.3克Silquest A 1230(来自CromptonChemicals，Middlebury，CT)和203.5克超纯水，并加热到80℃持续18个小时。
组合物II
将6.7克组合物I加到广口瓶中，并与93.3克超纯水结合。
组合物III
把15毫升组合物II加到体积为50毫升的烧瓶中，然后用超纯水稀释。
组合物IV
将5毫升组合物II加到50毫升的烧瓶中，然后用超纯水稀释。
实施例7-15的制剂见下表2。通过加入已知量的氯地米松二丙酸盐(BDP)至玻璃瓶，并加入10毫升下述纳米粒子中的一种来制备样品。把瓶盖好，振动约30秒，静置20分钟，观察分散体的稳定性并记录。
表2
| 样品 | 组合物(10毫升) | BDP的量(克) |
| 实施例7 | II | 0.1028 |
| 实施例8 | II | 0.0504 |
| 实施例9 | II | 0.0101 |
| 实施例10 | III | 0.1013 |
| 实施例11 | III | 0.0508 |
| 实施例12 | III | 0.0104 |
| 实施例13 | IV | 0.1015 |
| 实施例14 | IV | 0.0499 |
| 实施例15 | IV | 0.0104 |
| 样品 | 组合物(10毫升) | BDP的量(克) |
| 对比例A | 超纯水 | 0.1010 |
| 对比例B | 超纯水 | 0.0507 |
| 对比例C | 超纯水 | 0.0098 |
对比例A-C和实施例7-15的可视性比较结果
实施例7、10、13和对比例A的可视比较结果如下：对比例A中极少量的药剂分散在液态连续相中。大多数药剂保留在液态连续相的表面或保留在液面上方的瓶壁上。实施例7、10、13中显示出比对比例A多得多的药剂分散在液态连续相中，且在液面上或瓶壁上的药剂比对比例A中少。比较实施例7、10和13，表面改性纳米粒子的浓度越高使分散体表现出越高浓度的分散药剂。
上述观察结果对实施例8、11、14与对比例B，以及实施例9、12、15与对比例C也是正确的。
在不偏离本发明范围和主旨的前提下，本发明可预见的改进和变化对本领域的技术人员是显而易见的。本发明不受本申请中提到的实施方式的限制，这些实施方式仅为阐述的目的。
Claims (21)
1.一种分散体，包括
连续相，其包含液态连续相和表面改性的无机纳米粒子；和
分散相，其包含分散在液态连续相中的粒子，其中所述分散相包括一种或多种药剂粉末。
2.权利要求1的分散体，其中所述的液态连续相包含在水中的有机液体。
3.权利要求2的分散体，其中所述的液态连续相包含乙醇、丙二醇、甘油、乳酸酯或它们的组合物。
4.权利要求3的分散体，其中所述的液态连续相包含至少50wt％的水。
5.权利要求1-4中任一项的分散体，其中所述的纳米粒子选自二氧化硅、二氧化钛、氧化铝、氧化锆、氧化钒、磷酸钙、二氧化铈、氧化铁、氧化锑、氧化锡、铝/二氧化硅及其组合物。
6.权利要求1-4中任一项的分散体，其中所述的纳米粒子包括选自憎水基团、亲水基团及其组合的表面基团。
7.权利要求1-4中任一项的分散体，其中所述的纳米粒子包含选自聚乙二醇的表面亲水性基团。
8.权利要求1-4中任一项的分散体，其中所述的纳米粒子包含由选自硅烷、有机酸、有机碱及其组合的试剂衍生的表面基团。
9.权利要求1-4中任一项的分散体，其中所述的纳米粒子包含由选自烷基硅烷、芳基硅烷、烷氧基硅烷及其组合的试剂衍生的有机甲硅烷基表面基团。
10.权利要求1-4中任一项的分散体，其中所述的纳米粒子包含由选自羧酸、磺酸、磷酸及其组合的试剂衍生的表面基团。
11.权利要求1-4中任一项的分散体，其中所述的液态连续相选自水、有机酸、醇、酮、醛、胺、酰胺、酯、二醇、醚、烃、卤代烃、单体、低聚物、润滑剂、植物油、硅油、矿物油和希蒙得木油、燃料油、煤油、汽油、柴油、乙二醇的低聚物、烷基和芳基硝基化合物、部分或全部氟化的化合物，及它们的组合。
12.权利要求1-4中任一项的分散体，其中液态连续相进一步包括溶解的无机盐或有机盐、聚合物、赋形剂或其组合。
13.权利要求1-4中任一项的分散体，其中药剂选自类固醇、抗生素、支气管扩张剂或止痛剂。
14.权利要求1-4中任一项的分散体，其包含小于0.001wt％的表面活性剂。
15.权利要求1-4中任一项的分散体，进一步包含有机纳米粒子。
16.一种稳定分散体的方法，包括加入有效量的相容性表面改性无机纳米粒子至包含分散固相和液态连续相的分散体中，其中所述分散固相包括一种或多种药剂粉末。
17.包括药剂的分散粒子用于制备权利要求1-4中任一项的分散体的用途，所述分散体用于通过如下给药方式给药治疗有效量的所述药剂，所述给药方式选自口服给药、注射、局部施用、经鼻给药、吸入及其组合。
18.权利要求17的包括药剂的分散粒子的用途，其中所述给药方式是通过吸入给药。
19.权利要求18的包括药剂的分散粒子的用途，其中所述吸入给药包括利用雾化器。
20.权利要求17的包括药剂的分散粒子的用途，其中所述给药方式包括使用喷雾泵的经鼻给药或局部施用.
21.权利要求17的包括药剂的分散粒子的用途，其中所述给药方式是通过注射给药。
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Families Citing this family (55)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7109247B2 (en) | 2003-05-30 | 2006-09-19 | 3M Innovative Properties Company | Stabilized particle dispersions containing nanoparticles |
| US7828889B2 (en) * | 2003-12-18 | 2010-11-09 | The Clorox Company | Treatments and kits for creating transparent renewable surface protective coatings |
| US8974590B2 (en) | 2003-12-18 | 2015-03-10 | The Armor All/Stp Products Company | Treatments and kits for creating renewable surface protective coatings |
| CN101090712A (zh) * | 2004-11-15 | 2007-12-19 | 澳大利亚核科学技术组织 | 通过使微乳液受控去稳定得到的固体颗粒 |
| EP1846421A4 (en) * | 2005-01-20 | 2009-10-28 | Agency Science Tech & Res | WATER-SOLUBLE NANOPARTICLE WITH FUNCTIONALIZED SURFACE FOR BIOCONJUGATION BY UNIVERSAL SILANE COUPLING |
| US20070292688A1 (en) * | 2005-08-18 | 2007-12-20 | Eastman Kodak Company | Silylamine modified nanoparticulate carriers |
| RU2413740C2 (ru) * | 2005-08-25 | 2011-03-10 | Е.И.Дюпон Де Немур Энд Компани | Модифицированные наночастицы |
| JP4415972B2 (ja) | 2005-09-22 | 2010-02-17 | ソニー株式会社 | 金属酸化物ナノ粒子の製造方法 |
| US7629027B2 (en) * | 2005-10-14 | 2009-12-08 | 3M Innovative Properties Company | Method for making chromonic nanoparticles |
| US7718716B2 (en) * | 2005-10-14 | 2010-05-18 | 3M Innovative Properties Company | Chromonic nanoparticles containing bioactive compounds |
| KR100745744B1 (ko) * | 2005-11-11 | 2007-08-02 | 삼성전기주식회사 | 나노 입자 코팅 방법 |
| US7767736B2 (en) * | 2005-12-05 | 2010-08-03 | 3M Innovative Properties Company | Flame retardant polymer composition |
| US20070128291A1 (en) * | 2005-12-07 | 2007-06-07 | Tokie Jeffrey H | Method and Apparatus for Forming Chromonic Nanoparticles |
| US7807661B2 (en) * | 2005-12-08 | 2010-10-05 | 3M Innovative Properties Company | Silver ion releasing articles and methods of manufacture |
| ITFI20060006A1 (it) | 2006-01-04 | 2007-07-05 | Colorobbia Italiana Spa | Nanoparticelle funzionalizzate, loro produzione ed uso |
| US20100119697A1 (en) * | 2006-05-10 | 2010-05-13 | 3M Innovative Properties Company | Compositions and coatings containing fluorescent, inorganic nanoparticles |
| US20070275185A1 (en) * | 2006-05-23 | 2007-11-29 | 3M Innovative Properties Company | Method of making ordered nanostructured layers |
| KR100818462B1 (ko) | 2006-09-09 | 2008-04-01 | 재단법인서울대학교산학협력재단 | 폴리에틸렌글라이콜이 결합된 기능성 실리카 나노파티클 및그 제조방법 |
| US7632425B1 (en) * | 2006-10-06 | 2009-12-15 | General Electric Company | Composition and associated method |
| US20090297626A1 (en) * | 2006-11-03 | 2009-12-03 | The Trustees Of Columbia University In The City Of New York | Methods for preparing metal oxides |
| WO2009045723A1 (en) * | 2007-10-01 | 2009-04-09 | 3M Innovative Properties Company | Use of nanoparticles in explosives |
| DE102007058674A1 (de) * | 2007-12-06 | 2009-07-02 | Süd-Chemie AG | Nanopartikuläre Zusammensetzung und Verfahren zu deren Herstellung |
| CN101469250B (zh) | 2007-12-26 | 2012-09-19 | 3M创新有限公司 | 可去除的防雾涂层、制品、涂料组合物和方法 |
| IL188647A0 (en) | 2008-01-08 | 2008-11-03 | Orina Gribova | Adaptable structured drug and supplements administration system (for oral and/or transdermal applications) |
| FR2927005B1 (fr) * | 2008-02-05 | 2011-12-23 | Commissariat Energie Atomique | Materiau hybride organique-inorganique, couche mince optique de ce materiau, materiau optique les comprenant, et leur procede de fabrication |
| CN102076784A (zh) | 2008-05-08 | 2011-05-25 | 3M创新有限公司 | 表面改性的纳米粒子 |
| RU2011113979A (ru) * | 2008-09-11 | 2012-10-20 | Грейс Гмбх Унд Ко. Кг (De) | Дисперсия оксидов металлов |
| WO2010059812A1 (en) * | 2008-11-24 | 2010-05-27 | 3M Innovative Properties Company | Surface-modified metal phosphate nanoparticles |
| WO2010077773A1 (en) | 2008-12-30 | 2010-07-08 | 3M Innovative Properties Company | Lubricant composition and method of forming |
| US8741819B2 (en) | 2008-12-30 | 2014-06-03 | 3M Innovative Properties Company | Composite particles and method of forming |
| TWI384021B (zh) * | 2009-04-23 | 2013-02-01 | Ind Tech Res Inst | 奈米無機氧化物的相轉移方法 |
| US8673393B2 (en) * | 2009-06-08 | 2014-03-18 | Innovanano, Inc. | Hydrophobic materials made by vapor deposition coating and applications thereof |
| CN101941001B (zh) * | 2009-07-03 | 2014-04-02 | 3M创新有限公司 | 亲水涂层、制品、涂料组合物和方法 |
| CN102099011B (zh) | 2009-07-09 | 2016-06-01 | 奥莎迪药品管理有限公司 | 基质载体组合物、方法及用途 |
| KR101651915B1 (ko) * | 2009-09-14 | 2016-08-29 | 한화케미칼 주식회사 | 금속 나노입자 수계 분산액의 제조방법 |
| CN105858600A (zh) | 2010-04-23 | 2016-08-17 | 皮瑟莱根特科技有限责任公司 | 纳米晶体的合成、盖帽和分散 |
| US8835363B2 (en) | 2010-06-16 | 2014-09-16 | Saudi Arabian Oil Company | Drilling, drill-in and completion fluids containing nanoparticles for use in oil and gas field applications and methods related thereto |
| WO2012044287A1 (en) * | 2010-09-29 | 2012-04-05 | Empire Technology Development Llc | Phase change energy storage in ceramic nanotube composites |
| CN103108830B (zh) * | 2010-10-04 | 2014-07-16 | 3M创新有限公司 | 通过添加疏水性纳米粒子而改变粒子的溶解速率的方法 |
| EP2632849A4 (en) | 2010-10-27 | 2014-12-31 | Pixelligent Technologies Llc | SYNTHESIS, COVERAGE AND DISPERSION OF NANOCRYSTALLES |
| US9359689B2 (en) | 2011-10-26 | 2016-06-07 | Pixelligent Technologies, Llc | Synthesis, capping and dispersion of nanocrystals |
| US20140170395A1 (en) * | 2012-12-19 | 2014-06-19 | Hewlett-Packard Development Company, Lp | Durable metallic printing |
| WO2014140700A1 (en) * | 2013-03-14 | 2014-09-18 | University Of Calcutta | Methods of producing vanadium boride and uses thereof |
| WO2015066717A1 (en) | 2013-11-04 | 2015-05-07 | BioPharmX, Inc. | Dosage form comprising an active ingredient and a plurality of solid porous microcarriers |
| AU2016209538B2 (en) * | 2015-01-20 | 2019-05-30 | The Chemours Company Fc, Llc | Aqueous corrosion resistant coatings with surface-hydrophobic inorganic particles |
| CN106221297B (zh) * | 2016-07-25 | 2018-07-10 | 攀钢集团攀枝花钢铁研究院有限公司 | 提高钛白粉分散性的表面有机处理的方法 |
| US11123301B2 (en) | 2016-10-21 | 2021-09-21 | Cenyx Biotech Inc. | Ceria nanocomposite comprising ceria nanoparticle for treating subarachnoid hemorrhage, method for preparing same, and pharmaceutical composition |
| WO2018124363A1 (ko) | 2016-12-29 | 2018-07-05 | 서울대학교병원 | 생체의학적 치료용 세리아 나노복합체 및 이를 포함하는 약학적 조성물 |
| CN106810914A (zh) * | 2017-01-19 | 2017-06-09 | 南京威斯曼汽车服务有限公司 | 一种应用于汽车硬表面的涂层组合物 |
| EP3618811B1 (en) * | 2017-05-04 | 2020-09-30 | Nanologica AB | A process for manufacturing porous silica particles loaded with at least one bioactive compound adapted for lung, nasal, sublingual and/or pharyngeal delivery |
| WO2019164546A2 (en) * | 2017-08-14 | 2019-08-29 | Interphase Materials Inc. | Surface treatment |
| CN108424762B (zh) * | 2018-06-15 | 2020-08-21 | 天津新翔油气技术有限公司 | 一种水力压裂用的自悬浮支撑剂及其制备方法 |
| WO2020091948A1 (en) * | 2018-10-30 | 2020-05-07 | Croda, Inc. | A method of dispersing fine particles in an aqueous or polar solvent |
| US11999844B2 (en) * | 2020-03-09 | 2024-06-04 | Rohm And Haas Electronic Materials Llc | Optically clear shear thickening fluids and optical display device comprising same |
| CN113292915A (zh) * | 2021-05-18 | 2021-08-24 | 上海东恒化工有限公司 | 一种新型纳米粒子基复合脱模涂层 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1322228A (zh) * | 1998-10-06 | 2001-11-14 | 纳幕尔杜邦公司 | 具有改进稳定性的分散体 |
| WO2002053659A2 (en) * | 2001-01-08 | 2002-07-11 | 3M Innovative Properties Company | Energy curable inks and other compositions incorporating surface modified, nanometer-sized particles |
Family Cites Families (54)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE837243C (de) * | 1944-09-30 | 1952-04-21 | Bayer Ag | Schwebemittel fuer waessrige Suspensionen |
| US2801185A (en) * | 1952-05-16 | 1957-07-30 | Du Pont | Silica hydrosol powder |
| US3252859A (en) * | 1962-10-24 | 1966-05-24 | Masti Kure Company Inc | Colloidal silica-oil composition and method of using same |
| DE1467023A1 (de) * | 1964-02-28 | 1969-01-23 | Degussa | Verfahren zur Inkorporierung von Wasser in feinst verteilter Kieselsaeure |
| US3830738A (en) * | 1970-02-16 | 1974-08-20 | Ici Ltd | Surface treatment of particulate solids |
| US3963627A (en) * | 1970-02-16 | 1976-06-15 | Imperial Chemical Industries Limited | Surface treatment of particulate solids |
| US4680173A (en) * | 1977-04-28 | 1987-07-14 | Norman D. Burger | Aerosol dispensing system |
| FR2463056A1 (fr) * | 1979-08-09 | 1981-02-20 | Aerazur Constr Aeronaut | Dispositif pour le relevage du filet d'une barriere pour l'arret des avions |
| US4478876A (en) * | 1980-12-18 | 1984-10-23 | General Electric Company | Process of coating a substrate with an abrasion resistant ultraviolet curable composition |
| US4491508A (en) * | 1981-06-01 | 1985-01-01 | General Electric Company | Method of preparing curable coating composition from alcohol, colloidal silica, silylacrylate and multiacrylate monomer |
| US4455205A (en) * | 1981-06-01 | 1984-06-19 | General Electric Company | UV Curable polysiloxane from colloidal silica, methacryloyl silane, diacrylate, resorcinol monobenzoate and photoinitiator |
| US4486504A (en) * | 1982-03-19 | 1984-12-04 | General Electric Company | Solventless, ultraviolet radiation-curable silicone coating compositions |
| US4522958A (en) * | 1983-09-06 | 1985-06-11 | Ppg Industries, Inc. | High-solids coating composition for improved rheology control containing chemically modified inorganic microparticles |
| DE3333639A1 (de) * | 1983-09-17 | 1985-03-28 | Dynamit Nobel Ag | Zubereitung von nitroestern fuer die koronartherapie |
| US5145884A (en) * | 1986-11-13 | 1992-09-08 | Menicon Co., Ltd. | Ultraviolet-hardenable adhesive |
| US5210076A (en) * | 1988-09-13 | 1993-05-11 | Berliner David L | Methods of treating Parkinson's disease using melanin |
| US5037579A (en) * | 1990-02-12 | 1991-08-06 | Nalco Chemical Company | Hydrothermal process for producing zirconia sol |
| US5258225A (en) * | 1990-02-16 | 1993-11-02 | General Electric Company | Acrylic coated thermoplastic substrate |
| FR2666962B1 (fr) * | 1990-09-26 | 1996-06-14 | Oreal | Composition antifongique sous forme de spray sec. |
| FR2677544B1 (fr) * | 1991-06-14 | 1993-09-24 | Oreal | Composition cosmetique contenant un melange de nanopigments d'oxydes metalliques et de pigments melaniques. |
| FR2698002B1 (fr) * | 1992-11-13 | 1995-01-13 | Oreal | Composition cosmétique de maquillage contenant un fullerène ou un mélange de fullerènes comme agent pigmentant. |
| IL108416A (en) * | 1993-01-25 | 1998-10-30 | Sonus Pharma Inc | Colloids with phase difference as contrast ultrasound agents |
| US5492688A (en) * | 1993-04-28 | 1996-02-20 | The Center For Innovative Technology | Metered dose inhaler fomulations which include the ozone-friendly propellant HFC 134a and a pharmaceutically acceptable suspending, solubilizing, wetting, emulsifying or lubricating agent |
| DE69432224T2 (de) * | 1993-12-02 | 2003-12-04 | Abbott Lab | Aerosole als darreichungsform mit cfc-freiem treibmittel |
| US5480914A (en) * | 1994-05-06 | 1996-01-02 | Allergan, Inc. | Nonaqueous thixotropic drug delivery suspensions and methods of their use |
| IT1275955B1 (it) * | 1995-03-22 | 1997-10-24 | Dompe Spa | Formulazioni farmaceutiche in forma di gel tissotropico |
| US5648407A (en) * | 1995-05-16 | 1997-07-15 | Minnesota Mining And Manufacturing Company | Curable resin sols and fiber-reinforced composites derived therefrom |
| FR2739558B1 (fr) * | 1995-10-05 | 1997-11-28 | Innothera Lab Sa | Forme galenique unitaire pour hormonotherapie locale de la secheresse vaginale |
| FR2746302B1 (fr) * | 1996-03-20 | 1998-12-24 | Oreal | Compositions cosmetiques comprenant des nanopigments |
| FR2759582A1 (fr) * | 1997-02-14 | 1998-08-21 | Oreal | Composition deodorante |
| US6309623B1 (en) * | 1997-09-29 | 2001-10-30 | Inhale Therapeutic Systems, Inc. | Stabilized preparations for use in metered dose inhalers |
| DE19811790A1 (de) * | 1998-03-18 | 1999-09-23 | Bayer Ag | Nanopartikel enthaltende transparente Lackbindemittel mit verbesserter Verkratzungsbeständigkeit, ein Verfahren zur Herstellung sowie deren Verwendung |
| FR2781373B1 (fr) * | 1998-07-07 | 2001-09-21 | Pf Medicament | Formulations thixotropes pour le remplissage de gelules |
| US6319513B1 (en) * | 1998-08-24 | 2001-11-20 | The Procter & Gamble Company | Oral liquid mucoadhesive compounds |
| US7521068B2 (en) * | 1998-11-12 | 2009-04-21 | Elan Pharma International Ltd. | Dry powder aerosols of nanoparticulate drugs |
| DE19955719B4 (de) * | 1998-11-17 | 2017-08-17 | Kao Corp. | Farbtoner und dessen Verwendung |
| US6258896B1 (en) * | 1998-12-18 | 2001-07-10 | 3M Innovative Properties Company | Dendritic polymer dispersants for hydrophobic particles in water-based systems |
| US6238798B1 (en) * | 1999-02-22 | 2001-05-29 | 3M Innovative Properties Company | Ceramer composition and composite comprising free radically curable fluorochemical component |
| US6730156B1 (en) * | 1999-10-28 | 2004-05-04 | 3M Innovative Properties Company | Clustered particle dental fillers |
| US7412422B2 (en) * | 2000-03-23 | 2008-08-12 | Dekel Shiloh | Method and system for securing user identities and creating virtual users to enhance privacy on a communication network |
| FR2808704B1 (fr) * | 2000-05-10 | 2002-08-16 | Rhodia Chimie Sa | Agents tensioactifs formes par des particules minerales de dimension nanometrique de surface modifiee |
| DE10028974A1 (de) * | 2000-06-16 | 2002-01-03 | Henkel Kgaa | Thixotrope Mund- und Zahnpflegemittel |
| US20040081627A1 (en) * | 2000-10-09 | 2004-04-29 | Jinks Phillip A | Medicinal aerosol formulations |
| US6586483B2 (en) * | 2001-01-08 | 2003-07-01 | 3M Innovative Properties Company | Foam including surface-modified nanoparticles |
| JP4293735B2 (ja) * | 2001-01-19 | 2009-07-08 | 三栄源エフ・エフ・アイ株式会社 | フラーレン誘導体およびそれからなる組成物 |
| CA2467764A1 (en) * | 2001-12-21 | 2003-07-24 | Alcon, Inc. | Inorganic nanoparticles to modify the viscosity and physical properties of ophthalmic and otic compositions. |
| US7189417B2 (en) * | 2002-05-01 | 2007-03-13 | The Trustees Of The University Of Pennsylvania | Nanometer-sized carrier medium |
| US7141612B2 (en) * | 2002-12-31 | 2006-11-28 | 3M Innovative Properties Company | Stabilized foams including surface-modified organic molecules |
| US7129277B2 (en) * | 2002-12-31 | 2006-10-31 | 3M Innovative Properties Company | Emulsions including surface-modified inorganic nanoparticles |
| US7001580B2 (en) * | 2002-12-31 | 2006-02-21 | 3M Innovative Properties Company | Emulsions including surface-modified organic molecules |
| JP2004331883A (ja) * | 2003-05-09 | 2004-11-25 | Nissan Motor Co Ltd | 複合樹脂組成物中間体、複合樹脂組成物、複合樹脂組成物中間体の製造方法、及び複合樹脂組成物の製造方法 |
| US7109247B2 (en) * | 2003-05-30 | 2006-09-19 | 3M Innovative Properties Company | Stabilized particle dispersions containing nanoparticles |
| US7459146B2 (en) * | 2003-05-30 | 2008-12-02 | 3M Innovative Properties Company | Stabilized aerosol dispersions |
| US7649029B2 (en) * | 2004-05-17 | 2010-01-19 | 3M Innovative Properties Company | Dental compositions containing nanozirconia fillers |
-
2003
- 2003-05-30 US US10/449,359 patent/US20040242729A1/en not_active Abandoned
-
2004
- 2004-04-08 JP JP2006532386A patent/JP4662941B2/ja not_active Expired - Fee Related
- 2004-04-08 KR KR1020057022747A patent/KR101117846B1/ko not_active IP Right Cessation
- 2004-04-08 EP EP04749886A patent/EP1628750A2/en not_active Withdrawn
- 2004-04-08 CN CN2004800150639A patent/CN1798603B/zh not_active Expired - Fee Related
- 2004-04-08 WO PCT/US2004/010849 patent/WO2004108116A2/en active Application Filing
-
2008
- 2008-07-03 US US12/167,714 patent/US20080268062A1/en not_active Abandoned
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1322228A (zh) * | 1998-10-06 | 2001-11-14 | 纳幕尔杜邦公司 | 具有改进稳定性的分散体 |
| WO2002053659A2 (en) * | 2001-01-08 | 2002-07-11 | 3M Innovative Properties Company | Energy curable inks and other compositions incorporating surface modified, nanometer-sized particles |
Also Published As
| Publication number | Publication date |
|---|---|
| US20040242729A1 (en) | 2004-12-02 |
| CN1798603A (zh) | 2006-07-05 |
| JP2007500209A (ja) | 2007-01-11 |
| JP4662941B2 (ja) | 2011-03-30 |
| WO2004108116A3 (en) | 2005-03-17 |
| EP1628750A2 (en) | 2006-03-01 |
| KR20060056895A (ko) | 2006-05-25 |
| KR101117846B1 (ko) | 2012-03-15 |
| WO2004108116A2 (en) | 2004-12-16 |
| US20080268062A1 (en) | 2008-10-30 |
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