CN106176808A - 金属离子纳米簇组合物 - Google Patents
金属离子纳米簇组合物 Download PDFInfo
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- CN106176808A CN106176808A CN201610480938.7A CN201610480938A CN106176808A CN 106176808 A CN106176808 A CN 106176808A CN 201610480938 A CN201610480938 A CN 201610480938A CN 106176808 A CN106176808 A CN 106176808A
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- metal cation
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Abstract
本发明涉及一种含有多个直径介于2nm至500nm的水溶性纳米簇的组合物。这些纳米簇各自含有一或多种金属阳离子、一或多种阴离子及一或多种水溶性配体。本发明也揭示一种利用该组合物治疗各种不同疾病诸如贫血症、胃灼热及糖尿病的方法。
Description
本申请是2010年10月19日递交的中国专利申请201010516328.0的分案申请。
技术领域
本发明是关于一种水溶性纳米簇的组合物。本发明也揭示一种利用该组合物治疗各种不同疾病诸如贫血症、胃灼热及糖尿病的方法。
背景技术
已知某些金属离子为基本的营养物(包括微量养料)。缺乏这些离子导致一种或多种疾病诸如贫血(例如,由于缺铁症引起)、骨质疏松(例如,由于缺钙引起)、生长迟缓(例如,由于缺锌引起)及克山病(Keshan disease)(例如,由于缺硒引起)。治疗或预防这些疾病经常使用口服的、局部性的或注射补充品。
发明内容
在一方面,本发明提供一种包括多个直径介于2nm至500nm的水溶性纳米簇(例如,2至150nm、2至90nm、5至90nm或2至50nm)的组合物。这些纳米簇各自含有一或多种金属阳离子、一或多种阴离子及一或多种非聚合性水溶性配体。该一或多种非聚合性水溶性配体选自由单糖、加氢单糖、双糖、加氢双糖、寡糖、及寡糖衍生物所组成的群组。该一或多种金属阳离子、该一或多种阴离子及该一或多种非聚合性水溶性配体之间的摩尔比例为1:0.1~9:0.1~10(例如,1:0.5~3:1~4)。
在另一方面,本发明提供一种包括多个直径介于2nm至500nm的水溶性纳米簇(例如,2至150nm、2至90nm、5至90nm或2至50nm)的组合物。这些纳米簇各自含有一或多种金属阳离子、一或多种阴离子及一或多种水溶性配体。该一或多种金属阳离子是选自由Cr、Al、Bi、Zn、Ba、Cu、Ti、Mg、Mn、Bi、Ca、Se、In、Pt及Zr的阳离子所组成的群组。该一或多种水溶性配体是选自由碳水化合物衍生物、氨基酸、聚醚、聚醇及多肽所组成的群组。该一或多种金属阳离子、该一或多种阴离子及该一或多种水溶性配体之间的摩尔比例为1:0.1~9:0.1~10(例如,1:0.5~3:1~4)。
在又另一方面,本发明提供一种含铁的组合物,其包括多个直径介于2nm至500nm的水溶性纳米簇(例如,2至150nm、2至90nm、5至90nm或2至50nm)。这些纳米簇各自含有一或多种铁阳离子、一或多种阴离子及一或多种非聚合性水溶性配体。该一或多种非聚合性水溶性配体是选自由木糖醇、甘露醇、***糖、异麦芽糖、异麦芽、山梨醇及果寡糖所组成的群组。该一或多种铁阳离子、该一或多种阴离子及该一或多种非聚合性水溶性配体之间的摩尔比例为1:0.1~9:0.1~10(例如,1:0.5~3:1~4)。
用于文中时,措辞“碳水化合物”表示单糖类(例如,木糖、***糖、葡萄糖、甘露糖、果糖、半乳糖及核糖)、双糖类(例如,蔗糖、乳糖、异麦芽糖及异麦芽糖)、寡糖类(亦即,由3至9个单糖残基通过配糖键联连接的碳水化合物,例如棉子糖、松三糖、麦芽糖、阿卡波糖、水苏糖、果寡糖及乳寡糖类)及多糖类(例如,糊精及麦芽糊精)。措辞“碳水化合物衍生物”表示加氢碳水化合物(例如,木糖醇、***糖醇、甘露醇、山梨醇及异麦芽)或氧化的碳水化合物(例如,葡萄糖醛酸、葡萄糖醛酸钠及葡萄糖醛酸酯)。同样地,措辞“单糖衍生物”、“双糖衍生物”及“寡糖衍生物”表示其对应的氢化/氧化衍生物。
上述这些组合物的具体实施例可包括一或多种下列特征。该多个纳米簇可具有3,500至1,000,000道尔顿(例如,6,000至300,000道尔顿或10,000至120,000道尔顿)的分子量。该一或多种非聚合性水溶性配体是选自由木糖醇、甘露醇、***糖、异麦芽糖、异麦芽、山梨醇及果寡糖所组成的群组。该一或多种金属阳离子是选自由Fe(II)及Fe(III)所组成的群组。该一或多种金属阳离子是选自由Mg(II)、Al(III)、Ca(II)、Cr(III)、Cu(II)、Zn(II)、Mn(II)及Ti(IV)所组成的群组。该一或多种阴离子是选自由碳酸根、柠檬酸根、苹果酸根、反丁烯二酸根、酒石酸根、葡萄糖醛酸根、草酸根、丁二酸根、抗坏血酸根、焦磷酸根、甘油磷酸根及乳酸根所组成的群组。该组合物,无论呈干燥形态(例如,粉末或锭剂)、呈半固态(例如凝胶或乳霜)或呈液态(例如,饮料、糖浆、乳液或用于完全非经口营养的静脉内溶液),可为膳食增补剂、化妆组合物(例如,护肤或护发产品)或医药组合物。该组合物也可为食品。实例包括茶叶(例如,茶饮及茶包的内容物)、盐、酱、调味剂、糖果、咖啡、牛乳、烘焙食品(例如面包、饼干及糕饼)、饮料、果汁(例如,水果萃取液及水果饮料)、果酱、冰淇淋、酵母乳、谷物食品、巧克力类及点心棒。该组合物可为具有不大于10的pH值(例如,pH=7至10)的透明水溶液。
在一特定具体实施例中,当该组合物含有Fe(II)或Fe(III)时,该一或多种非聚合性水溶性配体是选自由山梨醇、木糖醇及异麦芽所组成的群组,及该一或多种阴离子是选自由碳酸根、重碳酸根、磷酸根、焦磷酸根、苹果酸根、甘油磷酸根及氢氧离子所组成的群组;或该一或多种非聚合性水溶性配体为蔗糖;及该一或多种阴离子是选自由碳酸根、柠檬酸根、苹果酸根、反丁烯二酸根、酒石酸根、草酸根、丁二酸根、抗坏血酸根、焦磷酸根、甘油磷酸根及乳酸根所组成的群组。
本发明的特征还有基本上由上述纳米簇所构成的组合物。文中所用的措辞“基本上由…所构成”将该组合物限于刚才提及的成分及那些不会大幅影响其基本和新颖特征者,亦即,不会大幅影响一或多种文中所述的症状(例如,贫血、糖尿病、肥胖症、骨质疏松、细菌性感染、皮肤疾病及胃逆流疾病)的治疗的有效性。此组合物的一实例含有刚才提及的纳米簇及医药、化妆品或膳食可接受的载剂。另一实例为含有这些纳米簇及各种不同非活性添加物(例如,赋形剂、甜味剂及人工调味)的组合物。
再者,本发明的特征为制造上述组合物的方法。该方法包括提供含有一或多种水溶性盐类和一或多种水溶性配体(例如,天然配体)的第一透明水溶液,及混合该第一透明水溶液与一或多种碱性阴离子以形成第二透明水溶液,其具有介于3.5与11之间(例如,6至10)的pH值,所以形成多个直径介于2nm至500nm(例如,2至150nm)的水溶性纳米簇,其各自含有该一或多种金属阳离子、该一或多种碱性阴离子及该一或多种水溶性配体。该一或多种水溶性盐类包括一或多种金属阳离子(例如,属于基本营养物的周期表2至15族金属的阳离子)。该一或多种水溶性配体是选自由碳水化合物、碳水化合物衍生物、氨基酸、聚醚、聚醇及多肽所组成的群组。在该第一透明水溶液中,该一或多种金属阳离子与该一或多种水溶性配体之间的摩尔比例为1:0.1至10(例如,1:0.5至3)。特别是,该方法所获得的多个水溶性纳米簇各自具有介于1:0.1至9:0.1至10(例如,1:0.5至3:1至4)之间的摩尔比例的一或多种金属阳离子、一或多种碱性阴离子及一或多种水溶性配体。
措辞“碱性阴离子”表示碱性化合物的阴离子,例如氢氧化钠、碳酸钠、重碳酸钠、柠檬酸钠、磷酸钠、甘油磷酸钠、焦磷酸钠等等。措辞“自然界存在的配体”或“天然配体”表示存在于天然界的非合成配体,例如木糖醇、蔗糖、葡萄糖醛酸、山梨醇及果寡糖。
上述方法可在少于10分钟内产生所述水溶性纳米簇。该方法可另外包括藉由通过于3,500至10,000道尔顿(例如,5,000道尔顿)截止的分子隔膜过滤该第二透明水溶液,或藉由将水溶性有机溶剂如醇加入该第二透明水溶液以沉淀出该多个水溶性纳米簇而分离该多个水溶性纳米簇与该第二透明水溶液。经分离的纳米簇可另外藉由已知方法予以干燥,例如空气干燥、烘箱干燥或喷干技术。
该方法中所用的一或多种水溶性配体较佳为存在于自然界中的碳水化合物,例如单糖、双糖、寡糖及其衍生物。应用存在于自然界中的配体不仅降低制造成本,缓和对于身体的负荷,而且也不会损坏生态环境。
在又另一方面,本发明提供一种借着视需要对病患投予有效量的上述组合物治疗缺铁症诸如缺铁贫血的方法,其中该一或多种金属阳离子包括铁阳离子。
在又另一方面,本发明提供一种借着视需要对病患投予有效量的上述组合物治疗糖尿病(例如,第II型糖尿病)或降低胆固醇量的方法,其中该一或多种金属阳离子包括铬阳离子。
本发明另提供一种借着视需要对病患投予有效量的上述组合物治疗胃逆流疾病(例如,胃灼热或胃肠溃疡)的方法,其中该一或多种金属阳离子是选自由铝阳离子、镁阳离子、铋阳离子及铁阳离子所组成的群组。
文中所述的纳米簇组合物也可作为生物成像剂(例如,作为MRI对比剂的含铁组合物或作为X-射线放射对比剂的含钡组合物)、护眼组合物(例如,含Zn或含Cu的组合物)、去头皮屑洗发剂(例如,含Zn组合物)、止汗剂或除臭剂(例如,含Al或含Cu的组合物)、抗氧化剂(例如,含Se组合物)、防晒剂(例如,含Ti组合物)、完全非经口营养注射液(例如,含Mg、Zn、Fe、Cu、Mn和Cr的组合物)或新陈代谢刺激物(例如,含In组合物)。就其本身而论,在另一方面,本发明提供一种视需要对病患投予有效量的上述组合物以治疗或预防一或多种下列疾病或状况:黄斑变性、晒伤、头皮屑及多汗症。
也在本发明范围以内的是含有上述用于治疗上述疾病或状况的组合物的组合物,及此组合物用于制造刚才提到的治疗药剂的用途。
预期该组合物的这些纳米簇也可作为药物载剂。举例来说,这些药物可经由离子键、共价键、氢键、偶极交互作用诸如范德华力连接于这些纳米簇的配体。关于另一实例,将该药物连至这些纳米簇的金属阳离子。
下文说明中将说明本发明的一或多个具体实施例的细节。本发明的其它特征、目的及优点从此说明内容及从申请专利范围将显而易见。
具体实施方式
本发明是至少部分基于下列意外发现,某些水溶性天然配体与金属阳离子和阴离子在一起会形成在广大范围的pH值间(例如,介于2与12之间)呈固态及在水溶液中均稳定的纳米簇。举例来说,本发明的一组合物,其含有蔗糖柠檬酸铁纳米簇,意外地是一种在6至10的pH呈现稳定的透明溶液,而且因此同时适用于静脉内注射及肌肉内注射。相比之下,市面上可购得的蔗糖铁注射液具有10.5至11.1的pH而且因此不适用于肌肉内注射。商业上的蔗糖铁注射液的高pH似乎也会造成蔗糖的水解,导致pH下降,其明显降低产物稳定性而且因此缩短该产物的储藏时间。关于另一实例,本发明的一组合物,其含有完全非经口营养注射液中所需的金属阳离子(例如Mg、Zn、Fe、Cu、Mn及Cr),意外地是一种于4至10的pH呈现稳定的透明溶液,而且因此,对比于pH为2的商业上的电解质注射液,将不会引起任何组织刺激。
此外,不像对应的自由金属阳离子,这些纳米簇意外地可口并且可与各种不同膳食增补剂兼容,例如蛋白质(例如,胶原)、胜肽、维他命(例如,维他命A、D及E)、辅酶(例如,Q10)、胡萝卜素、姜黄素、甜味剂及咖啡因等。文中所述的组合物的其它优点包括其生理或低克分子渗透浓度(osmolarity)、透明优越性及经过长时间(例如,数年)不会沉积的物理稳定性。
用于形成这些纳米簇的配体较佳为溶于水中并且接于金属阳离子强到足以形成数纳米至数百纳米规模的聚集体的天然有机配体。适合配体的实例包括但不限于例如糖醇的多羟醇类或多羟醚类以及其羧烷基-、氨基-、酰胺基-或酯-衍生物、单糖类、双糖类、多糖类(例如,葡聚糖及糊精)、水解多糖(例如,水解淀粉)、寡糖类及水解寡糖类。为了制造一整批纳米簇可使用多于一类的配体。
用于形成这些纳米簇的金属阳离子为必要养分或在化妆或医药上有利的。这些金属阳离子的实例包括铬、铝、铋、锌、钡、铜、钛、镁、钙、铁、硒、锰、铟及其混合物的阳离子。
用于形成这些纳米簇的阴离子可任意为无机阴离子(其包括氯离子、氢氧离子、硝酸根、硫酸根、重碳酸根、碳酸根、磷酸根、焦磷酸根、甘油磷酸根等等)或有机阴离子(其包括柠檬酸根、苹果酸根、反丁烯二酸根、酒石酸根及葡萄糖醛酸根等)。要制造一整批纳米簇可使用多于一类的阴离子。
本发明的含纳米簇的组合物可藉由各种不同技术来形成。在一具体实施例中,其是于适合温度(例如,15至135℃或较佳65至95℃)及pH值(例如,对于大部分金属阳离子/配体pH 4至9及用于形成含镁的或含蔗糖的纳米簇pH 9至11.5)下在水中混合水溶性金属盐(例如,氯化铁)、配体(例如,木糖醇)及碱性试剂(例如,氢氧化钠)历经所选的处理时间(例如,数分钟至数小时)。由此所形成的纳米簇经常介于2nm至500nm的直径(或较佳3至50nm),藉由动态激光散射技术来测定,如B.J.Berne等人“Dynamic Light Scattering”,J.Wileyand Sons股份有限公司,纽约,1976年;P.J.Freud等人,“A New Approach to particleSizing by Dynamic Light Scattering”,Microtrac股份有限公司;及M.N.Trainer等人,“High-concentration submicron particle size distribution by dynamic lightscattering”,American Laboratory,1992年7月中所述的。含有这些纳米簇的水溶液,由于其小尺寸,显得透明又优越。为了分离这些纳米簇与该溶液的其它成分(例如,未反应的自由金属阳离子、阴离子、盐类及水溶性配体,可以应用例如过滤(例如,使用具有所选的分子截止作用的隔膜)及沉淀(例如,使用例如乙醇的水溶性有机溶剂)的技术。接着可干燥及磨细分离出来的纳米簇以获得粉末状固体。该纳米簇粉末为热稳定性而且可用于面包店配方及非经口配方中。该粉末状固体也可再溶于水中以形成透明溶液,其能与各种饮料兼容,例如不含酒精的饮料、牛奶及咖啡。
本发明的组合物中的金属阳离子、阴离子及配体之间的摩尔比例可为1:0.1至9:0.1至10,或于其间的任何比例。经常地,病患(例如,人类或动物)可每天被投予一次或周期性地投予,能提供0.03至2000mg的所需金属离子量的组合物。举例来说,单剂组合物可提供500至1500mg的钙、0.04至0.2mg的铬、0.5至5mg的铜、5至15mg的铁、150至350mg的镁、1至5mg的镁、0.025至0.15mg的钼、0.01至0.1mg的硒、0.01至1mg的镍、0.01至1mg的钒及/或5至20mg的锌。
本发明的组合物可为膳食增补剂、化妆品或医药组合物。关于膳食增补剂,可包括其它营养物,例如矿物质、氨基酸或药草萃取液。关于其它化妆品,其它成分,例如保湿剂、增白剂、抗氧化剂或药草萃取液。关于医药组合物(其形态包括但不限于粉末、胶囊、锭剂、乳化物及含水悬浮液、分散液及溶液),本发明的组合物可单独使用或与医药上可接受的载剂合并使用。在用于口服用途的锭剂的案例中,常用的载剂包括乳糖及玉米淀粉。润滑剂,例如硬脂酸镁也经常添加。关于胶囊形态的口服投药,有用的稀释剂包括乳糖及干玉米淀粉。当含水悬浮液或乳化物经口投予时,有效成分可悬浮于或溶于与乳化剂或悬浮剂合并的水相中。必要的话,可添加若干甜味剂、调味剂或着色剂。在可与该配方的有效成分兼容(而且较佳地,可使其稳定化)及不会对治疗的病患不利的方面该医药组合物中的载剂必须为“可接受的”。其它载剂的实例包括胶体二氧化硅、硬脂酸镁、月桂基硫酸钠及D&CYellow#10。
该组合物也可为食品。用于文中时,措辞“食物”广泛表示用于滋补人类和动物,用于保持正常或加速成长,或用于维持持久力或警觉的任何种类的液态及固态/半固态材料。人类食品的实例包括,但不限于,茶类饮料、果汁、咖啡、牛奶、果酱、饼干、谷物食品、面包、甜甜圈、硬面包圈(bagel)、巧克力类、点心棒、药草萃取液、奶酪制品(例如,冰淇淋及酵母乳)、大豆产品(例如,豆腐)及米制品。
本发明的组合物可呈各种不同形态。当上述组合物呈粉末状时,其可方便地用以制备饮料、糊状物、果酱、胶囊或锭剂。乳糖及玉米淀粉常用作为胶囊用的稀释剂及锭剂用的载剂。锭剂中经常包括润滑剂,例如硬脂酸镁。关于另一实例,其可为包括上述纳米簇、烟酰胺、抗坏血酸、抗坏血酸钠、叶酸、糖、玉米糖浆、蔗糖素、大豆卵磷脂、玉米淀粉、甘油、棕榈油、木糖醇、鹿角菜胶、FD&C Yellow#6、FD&C Yellow#5及天然及/或人工调味的软糖组合物。
本发明的组合物可另外含有下列之一或多种:表棓儿茶素没食子酸酯(epigallocatechin gallate;EGCG)、CoQ10、黄体素、西红柿红素、二十碳五烯酸、二十二碳六烯酸大豆异黄酮素类、叶酸及维他命B12。再者,必要的话,其可藉由添加甜味剂变甜,例如山梨醇、麦芽糖醇、加氢葡萄糖浆及加氢淀粉水解产物、高果糖玉米糖浆、蔗糖、甜菜糖、果胶、木糖醇、糖精、阿斯巴甜及蔗糖素。该组合物也可含有氨基酸类、矿物质类、风味增进剂或着色剂。
本发明的组合物,当含有铁时,可用以治疗缺铁症诸如缺铁贫血。此类型贫血的实例包括与慢性出血、急性出血、怀孕、分娩、幼年成长、心理性肌肉运动及儿童认知发现、婴儿摒息症(breath-holding spells)、重度子宫出血、月经期间、慢性反复性咳血、特发性肺部铁质沉着病、慢性内出血、胃肠出血、感染寄生虫、慢性肾病、渗析、化学治疗、手术或急性外伤、慢性摄取酒精、水杨酸盐、类固醇、非类固醇类抗发炎剂或红血球生成刺激剂相关的贫血。在一些方面,该贫血为慢性疾病的贫血,例如类风湿性关节炎、癌症、霍奇金氏白血病(Hodgkins leukemia)、非霍奇金氏白血病、癌症化学治疗、炎症性肠病、溃疡性结肠炎甲状腺炎、肝炎、全身性红斑狼疮、风湿性多发性肌痛、硬皮病、混合***疾病、鸠氏症候群(Sojgren's syndrome)、郁血性心脏衰竭/心肌症或特发性老人贫血。又在有些具体实施例中,该贫血是由于受抑的铁吸收或营养不良,例如与克隆氏病(Crohn's Disease)、胃手术、摄取抑制铁吸收的药物及长期使用钙相关的贫血。
在其它具体实施例中,本发明的组合物,当含有铬时,可用以治疗糖尿病(例如第II型糖尿病),降低胆固醇量及治疗肥胖;当含有镁及铝/铁,可作为制酸剂;或当含有Mg、Mn、Cr、Zn及Cu离子,可作为完全非经口营养注射液。
措辞“治疗”表示对病患投予有效量的本发明的组合物,该病患必需改善一或多种上述状况或具有一或多种刚才提到的症状,或这些疾病或状况之一或多种的征候或体质,目的在于改善一或多种这些状况,或预防,治愈,缓解,减轻,治疗或改善一或多种这些症状,或其中一或多者的征候或体质。
措辞“投予”涵盖口服、局部性或非经口递送给病患任何适合形态的本发明的组合物,例如,食品、饮料、锭剂、胶囊、悬浮液、乳液、乳霜、凝胶及溶液。措辞“非经口”表示皮下、皮内、静脉内、肌肉内、关节内、动脉内、关节滑液内、胸骨内、鞘内、病变内及头颅内注射以及各种不同点滴注射技术。必要的话,可利用适合的分散剂或润湿剂(例如Tween 80)和悬浮剂依据此技艺中已知的技术调配无菌的可注射组合物,例如,无菌的可注射水性或油性悬浮液。该无菌的可注射制剂也可为在无毒性非经口可接受的稀释剂或溶剂中的无菌注射溶液或悬浮液,举例来说,像是在1,3-丁二醇、丙二醇或甘油中的溶液。可加以运用的可接受性溶液及溶剂为木糖醇、甘露醇、水、林格氏液(Ringer’s solution)及等张食盐水。此外,习惯上以无菌的定性油作为溶剂或悬浮媒介(例如,合成的单-或双甘油酯类)。脂肪酸类,例如油酸及其甘油酯衍生物可用于血管注射剂的制备,像是天然的医药上可接受的油类,例如橄榄油或蓖麻油,尤其是其聚氧乙基化的形式。这些油溶液或悬浮液也可含有长链醇稀释剂或分散剂,或羧甲基纤维素或类似的分散剂。其它例如Tweens或Spans的常用的表面活性剂或其它在制造医药上可接受的固态、液态或其它配药形态时常用的类似乳化剂或生物可利用增进剂也可用于调配的用途。
“有效量”表示充分提供身体益处(例如,改善持久力)、心理益处(例如,警觉性)、外观益处(例如,抗皱纹)或治疗益处(例如,降低胆固醇量,或降低贫血的风险)的组合物剂量。在活体内或活体外研究中均可进行以判定最理想的投予途径及剂量。
上述组合物可藉由活体外检定并且接着藉由动物实验及临床试验预先筛选其治疗上述状况时的效力。其它适合的分析及生物检定法对于普通熟悉此技艺者而言显而易见。举例来说,含铁纳米簇的生物利用性可藉由进行药物动力学研究来测量并且藉由血浆-药物浓度时间曲线中的曲线下面积配合治疗终点验证诸如血红素、铁蛋白浓度等等来评估。
无需进一步阐述,相信上述说明已经能充分地完成本发明。因此,把下列实施例解释仅为了举例说明,而非以任何方式限制此揭示内容剩余部分。文中所引用的所有刊物在此以引用方式将其全文并入本文。
实施例1:木糖醇碳酸铁纳米簇
配合搅拌将3000g的木糖醇及700g氯化铁六水合物溶于6000g于70℃的水中以制造溶液。藉由迅速添加一份适合量的含有20重量%的碳酸钠的水溶液把该溶液的pH提高至7左右。藉由迅速添加一份适合量的含有20重量%的氢氧化钠的水溶液把该溶液的pH提高至9。在此pH调节的期间使温度维持于70℃。在添加NaOH之后的10分钟内,接着获得具有强烈激光散射特性的透明溶液。此强烈的激光散射性质指示形成木糖醇碳酸铁纳米簇。通过横流隔膜过滤利用分子量截止于3500道尔顿的隔膜从溶剂及自由离子分离出这些纳米簇。分离出来的纳米簇进一步于80℃的烘箱中干燥以形成深红色固体,进一步把其磨细为自由流动粉末。由此所获得的纳米簇的原子吸收光谱指示这些纳米簇具有25重量%的铁含量。
亦可将该纳米簇的干燥固体再溶于水中以形成具有强烈激光散射特性的透明溶液,该纳米簇的固态与液态之间有可逆性及好的热稳定性。此纳米簇铁溶液也不再有金属的刺激口味。该纳米簇的干燥固体亦可迅速溶于0.1N HCl水溶液。此为有用的铁生体可用率的测试方法。铁生体可用率的测试方法被详细描述在如下文献:“A Comparison ofPhysical Properties,Screening Procedures and Human Efficacy Trial ForPredicting The Bioavailability of Commercial Elemental Iron Powders Used ForFood Fortification”published by Sean R.Lynch,Thomas Bothwell and the SUSTAIN(Sharing United States Technology to Aid in the Improvement of Nutrition)TaskForce on Iron Powder in Int.J.Vitam.Nutr.Res.,77(2),2007,107-124以及“A newtool to evaluate iron bioavailability”in Nutriview,2008/3。
此木糖醇铁溶液可与维他命B12及叶酸混合,再加入于60℃的含有各种不同蛋白质诸如猪皮胶原及Colla Corii Asini(阿胶;Donkey hide gelatin)以及甘油的水溶液。把所得的溶液冷却至25℃以形成没有沉淀也没有金属味道且适口又透明的弹性膜。此产品则适用于贫血治疗。
实施例2:木糖醇氢氧化铁纳米簇
配合搅拌将5472g的木糖醇及5500g的氯化铁六水合物溶于2700g于85℃的水中以制造溶液。藉由迅速添加一份适合量的含有20重量%的氢氧化钠的水溶液把该溶液的pH提高至9。在添加NaOH之后的10分钟内,接着获得具有强烈激光散射特性的透明溶液。此强烈的激光散射性质指示形成木糖醇氢氧化铁纳米簇。通过横流隔膜过滤利用分子量截止于3500道尔顿的隔膜从溶剂及自由离子分离出这些纳米簇。分离出来的纳米簇进一步于80℃的烘箱中干燥以形成深红色固体,进一步把其磨细为自由流动粉末。由此所获得的纳米簇的原子吸收光谱指示这些纳米簇具有24.3重量%的铁含量。
亦可将该纳米簇的干燥固体再溶于水中以形成具有强烈激光散射特性的透明溶液,该纳米簇的固态与液态之间有可逆性及好的热稳定性。此溶液尝不出金属味道。该纳米簇的干燥固体亦可迅速溶于0.1N HCl水溶液。铁生体可用率的测试方法被详细描述在如下文献:“A Comparison of Physical Properties,Screening Procedures and HumanEfficacy Trial For Predicting The Bioavailability of Commercial ElementalIron Powders Used For Food Fortification”published by Sean R.Lynch,ThomasBothwell and the SUSTAIN(Sharing United States Technology to Aid in theImprovement of Nutrition)Task Force on Iron Powder in Int.J.Vitam.Nutr.Res.,77(2),2007,107-124以及“A new tool to evaluate iron bioavailability”inNutriview,2008/3。
实施例3:甘露醇氢氧化铁纳米簇
配合搅拌将1500g的甘露醇及856g的氯化铁六水合物溶于3000g于85℃的水中以制造溶液。藉由迅速添加一份适合量的含有20重量%的氢氧化钠的水溶液把该溶液的pH提高至9。在添加NaOH之后的10分钟内,接着获得具有强烈激光散射特性的透明溶液。继续搅拌该溶液直至残余的小胶状体都溶解。此强烈的激光散射性质指示形成甘露醇氢氧化铁纳米簇。通过横流隔膜过滤利用分子量截止于3500道尔顿的隔膜从溶剂及自由离子分离出这些纳米簇。分离出来的纳米簇进一步于80℃的烘箱中干燥以形成深红色固体,进一步把其磨细为自由流动粉末。由此所获得的纳米簇的原子吸收光谱指示这些纳米簇具有19.23重量%的铁含量。
亦可将该纳米簇的干燥固体再溶于水中以形成具有强烈激光散射特性的透明溶液,该纳米簇的固态与液态之间有可逆性及好的热稳定性。此溶液尝不出金属味道。该纳米簇的干燥固体亦可迅速溶于0.1N HCl水溶液。铁生体可用率的测试方法被详细描述在如下文献:“A Comparison of Physical Properties,Screening Procedures and HumanEfficacy Trial For Predicting The Bioavailability of Commercial ElementalIron Powders Used For Food Fortification”published by Sean R.Lynch,ThomasBothwell and the SUSTAIN(Sharing United States Technology to Aid in theImprovement of Nutrition)Task Force on Iron Powder in Int.J.Vitam.Nutr.Res.,77(2),2007,107-124以及“A new tool to evaluate iron bioavailability”inNutriview,2008/3。
实施例4:异麦芽氢氧化铁纳米簇
配合搅拌将688g的异麦芽及556g的氯化铁六水合物溶于2000g于80℃的水中以制造溶液。藉由迅速添加一份适合量的含有20重量%的氢氧化钠的水溶液把该溶液的pH提高至8.5。在添加NaOH之后的10分钟内,接着获得具有强烈激光散射特性的透明溶液。此强烈的激光散射性质指示形成异麦芽氢氧化铁纳米簇。通过横流隔膜过滤利用分子量截止于3500道尔顿的隔膜从溶剂及自由离子分离出这些纳米簇。分离出来的纳米簇进一步于80℃的烘箱中干燥以形成深红色固体,进一步把其磨细为自由流动粉末。由此所获得的纳米簇的原子吸收光谱指示这些纳米簇具有17.6重量%的铁含量。
亦可将该纳米簇的干燥固体再溶于水中以形成具有强烈激光散射特性的透明溶液,该纳米簇的固态与液态之间有可逆性及好的热稳定性。此溶液尝不出金属味道。该纳米簇的干燥固体亦可迅速溶于0.1N HCl水溶液。铁生体可用率的测试方法被详细描述在如下文献:“A Comparison of Physical Properties,Screening Procedures and HumanEfficacy Trial For Predicting The Bioavailability of Commercial ElementalIron Powders Used For Food Fortification”published by Sean R.Lynch,ThomasBothwell and the SUSTAIN(Sharing United States Technology to Aid in theImprovement of Nutrition)Task Force on Iron Powder in Int.J.Vitam.Nutr.Res.,77(2),2007,107-124以及“A new tool to evaluate iron bioavailability”inNutriview,2008/3。
实施例5:山梨醇碳酸铁纳米簇
配合搅拌将1820g的山梨醇及2880g的氯化铁六水合物溶于1000g于85℃的水中以制造溶液。藉由迅速添加一份适合量的含有20重量%的碳酸钠的水溶液把该溶液的pH提高至9。在添加Na2CO3之后的10分钟内,接着获得具有强烈激光散射特性的透明溶液。此强烈的激光散射性质指示形成山梨醇碳酸铁纳米簇。通过横流隔膜过滤利用分子量截止于3500道尔顿的隔膜从溶剂及自由离子分离出这些纳米簇。分离出来的纳米簇进一步于80℃的烘箱中干燥以形成深红色固体,进一步把其磨细为自由流动粉末。由此所获得的纳米簇的原子吸收光谱指示这些纳米簇具有22.1重量%的铁含量。
亦可将该纳米簇的干燥固体再溶于水中以形成具有强烈激光散射特性的透明溶液,该纳米簇的固态与液态之间有可逆性及好的热稳定性。此溶液尝不出金属味道。该纳米簇的干燥固体亦可迅速溶于0.1N HCl水溶液。铁生体可用率的测试方法被详细描述在如下文献:“A Comparison of Physical Properties,Screening Procedures and HumanEfficacy Trial For Predicting The Bioavailability of Commercial ElementalIron Powders Used For Food Fortification”published by Sean R.Lynch,ThomasBothwell and the SUSTAIN(Sharing United States Technology to Aid in theImprovement of Nutrition)Task Force on Iron Powder in Int.J.Vitam.Nutr.Res.,77(2),2007,107-124以及“A new tool to evaluate iron bioavailability”inNutriview,2008/3。
实施例6:柠檬酸蔗糖碳酸铁纳米簇
配合搅拌将800g的蔗糖、110g的柠檬酸及278g的氯化铁六水合物溶于1200g于85℃的水中以制造溶液。藉由迅速添加一份适合量的含有20重量%的碳酸钠的水溶液把该溶液的pH提高至约7。在添加Na2CO3之后的10分钟内,接着获得具有强烈激光散射特性的透明溶液。此强烈的激光散射性质指示形成柠檬酸蔗糖碳酸铁纳米簇。通过横流隔膜过滤利用分子量截止于3500道尔顿的隔膜从溶剂及自由离子分离出这些纳米簇。分离出来的纳米簇进一步于80℃的烘箱中干燥以形成深红色固体,进一步把其磨细为自由流动粉末。由此所获得的纳米簇的原子吸收光谱指示这些纳米簇具有15.7重量%的铁含量。
接着将该纳米簇的干燥固体再溶于水中以形成具有强烈激光散射特性的透明溶液,指示固态与液态之间的纳米簇的可逆性及其热稳定性。此溶液尝不出金属味道。该纳米簇的干燥固体亦可迅速溶于0.1N HCl水溶液。铁生体可用率的测试方法被详细描述在如下文献:“A Comparison of Physical Properties,Screening Procedures and HumanEfficacy Trial For Predicting The Bioavailability of Commercial ElementalIron Powders Used For Food Fortification”published by Sean R.Lynch,ThomasBothwell and the SUSTAIN(Sharing United States Technology to Aid in theImprovement of Nutrition)Task Force on Iron Powder in Int.J.Vitam.Nutr.Res.,77(2),2007,107-124以及“A new tool to evaluate iron bioavailability”inNutriview,2008/3。
实施例7:木糖醇葡萄糖酸苹果酸氢氧化铁铜纳米簇
配合搅拌将300g的木糖醇、90g的葡萄糖醛酸钠、90g的苹果酸、10g的氯化铜脱水物及278g氯化铁六水合物溶于600g于80℃的水中以制造溶液。藉由迅速添加一份适合量的含有20重量%的氢氧化钠的水溶液把该溶液的pH提高至约8。在添加NaOH之后的10分钟内,接着获得具有强烈激光散射特性的透明溶液。此强烈的激光散射性质指示形成木糖醇葡萄糖酸苹果酸氢氧化铁铜纳米簇。通过横流隔膜过滤利用分子量截止于3500道尔顿的隔膜从溶剂及自由离子分离出这些纳米簇。分离出来的纳米簇进一步于80℃的烘箱中干燥以形成深红色固体,进一步把其磨细为自由流动粉末。由此所获得的纳米簇的原子吸收光谱指示这些纳米簇具有18.87重量%的铁含量和0.87重量%的铜含量。
亦可将该纳米簇的干燥固体再溶于水中以形成具有强烈激光散射特性的透明溶液,该纳米簇的固态与液态之间有可逆性及好的热稳定性。
实施例8:山梨醇苹果酸碳酸镁铁铜纳米簇
配合搅拌将500g的山梨醇、402g的苹果酸、256g的氯化铁六水合物、17g的氯化铜脱水物及406g的氯化镁六水合物溶于500g于80℃的水中以制造溶液。藉由迅速添加一份适合量的含有20重量%的碳酸钠的水溶液把该溶液的pH提高至约7。在添加Na2CO3之后的10分钟内,接着获得具有强烈激光散射特性的透明溶液。此强烈的激光散射性质指示形成山梨醇苹果酸碳酸镁铁铜纳米簇。通过横流隔膜过滤利用分子量截止于3500道尔顿的隔膜从溶剂及自由离子分离出这些纳米簇。分离出来的纳米簇进一步于80℃的烘箱中干燥以形成深红色固体,进一步把其磨细为自由流动粉末。由此所获得的纳米簇的原子吸收光谱指示这些纳米簇具有15.4重量%的铁含量,6重量%的镁含量,和0.82重量%的铜含量。
接着将该纳米簇的干燥固体再溶于水中以形成具有强烈激光散射特性的透明溶液,指示固态与液态之间的纳米簇的可逆性及其热稳定性。
实施例9:柠檬酸木糖醇氢氧化镁铁纳米簇
配合搅拌将300g的木糖醇、162.4g的氯化镁六水合物、111.2g的氯化铁六水合物及120g的柠檬酸溶于400g于80℃的水中以制造溶液。藉由迅速添加一份适合量的含有20重量%的氢氧化钠的水溶液把该溶液的pH提高至约7。在添加NaOH之后的5分钟内,接着获得具有强烈激光散射特性的透明溶液。此强烈的激光散射性质指示形成柠檬酸木糖醇氢氧化镁铁纳米簇。通过横流隔膜过滤利用分子量截止于3500道尔顿的隔膜从溶剂及自由离子分离出这些纳米簇。分离出来的纳米簇进一步于80℃的烘箱中干燥以形成深红色固体,进一步把其磨细为自由流动粉末。由此所获得的纳米簇的原子吸收光谱指示这些纳米簇具有15.21重量%的铁含量和6.3重量%的镁含量。
亦可将该纳米簇的干燥固体再溶于水中以形成具有强烈激光散射特性的透明溶液,该纳米簇的固态与液态之间有可逆性及好的热稳定性。此溶液尝不出金属味道。
实施例10:山梨醇柠檬酸氢氧化镁纳米簇
配合搅拌将722g的山梨醇、624g的氯化镁六水合物及208g的柠檬酸单水合物溶于2020g 70℃的水中以制造溶液。藉由添加含有20重量%的氢氧化钠的水溶液把该溶液的pH提高至8。在添加NaOH之后,就获得具有强烈激光散射特性的无色透明山梨醇柠檬酸氢氧化镁纳米簇溶液。此强烈的激光散射性质指示形成山梨醇柠檬酸氢氧化镁纳米簇。接着把乙醇加入该溶液以沉淀出该山梨醇柠檬酸氢氧化镁纳米簇。或通过横流隔膜过滤利用分子量截止于3500道尔顿的隔膜从溶剂及自由离子分离出这些纳米簇。分离出来的纳米簇进一步于80℃的烘箱中干燥以形成固体。由此所获得的纳米簇的原子吸收光谱指示这些纳米簇具有7.69重量%的镁含量。
接着将该纳米簇的干燥固体再溶于水中以形成具有强烈激光散射特性的透明溶液,此证明此纳米簇的固态与液态之间是有可逆性及热稳定性。此所得的干燥固体或透明溶液具有良好的酸中和力而没有金属味道。接下来,此纳米簇的固态与液态能与各种不同食品或药品赋形剂混合以供进营养品或药品的开发应用。
实施例11:山梨醇柠檬酸氢氧化铝纳米簇
配合搅拌将800g的山梨醇、600g的氯化铝六水合物及250g的柠檬酸单水合物溶于3000g 70℃的水中以制造溶液。藉由添加含有20重量%的氢氧化钠的水溶液把该溶液的pH提高至8。在添加NaOH之后,就获得具有强烈激光散射特性的无色透明山梨醇柠檬酸氢氧化铝纳米簇溶液。此强烈的激光散射性质指示形成山梨醇柠檬酸氢氧化铝纳米簇。接着把乙醇加入该溶液以沉淀出该山梨醇柠檬酸氢氧化铝纳米簇。或通过横流隔膜过滤利用分子量截止于3500道尔顿的隔膜从溶剂及自由离子分离出这些纳米簇。分离出来的纳米簇进一步于80℃的烘箱中干燥以形成固体。
接着将该纳米簇的干燥固体再溶于水中以形成具有强烈激光散射特性的透明溶液,此证明此纳米簇的固态与液态之间是有可逆性及热稳定性。此所得的干燥固体或透明溶液具有良好的酸中和力而没有金属味道。接下来,此纳米簇的固态与液态能与各种不同药品赋形剂混合以供药品的开发应用。
实施例12:木糖醇氢氧化铬纳米簇
配合搅拌将600g的木糖醇及140g的氯化铬(III)六水合物溶于1200g于85℃的水中以制造溶液。藉由迅速添加一份适合量的含有20重量%的氢氧化钠的水溶液把该溶液的pH提高至约9。在20分钟内,接着获得具有强烈激光散射特性的蓝色透明溶液。此强烈的激光散射性质指示形成木糖醇铬纳米簇。通过横流隔膜过滤利用分子量截止于3500道尔顿的隔膜从溶剂及自由离子分离出这些纳米簇。分离出来的纳米簇进一步于80℃的烘箱中干燥以形成蓝色固体,进一步把其磨细为自由流动粉末。由此所获得的纳米簇的原子吸收光谱指示这些纳米簇具有8.19重量%的铬含量。
亦可将该纳米簇的干燥固体再溶于水中以形成具有强烈激光散射特性的透明溶液,该纳米簇的固态与液态之间有可逆性及好的热稳定性。此溶液尝不出金属味道。
实施例13:***糖碳酸铬纳米簇
配合搅拌将30g的***糖及7g的氯化铬六水合物溶于60g于70℃的水中以制造溶液。藉由添加含有20重量%的碳酸钠的水溶液把该溶液的pH提高至约4。藉由迅速添加一份适合量的含有20重量%的氢氧化钠的水溶液把该溶液的pH进一步提高至10。接着将温度提高至90℃。在温度达到90℃之后的10分钟内,接着获得具有强烈激光散射特性的透明溶液。此强烈的激光散射性质指示形成***糖碳酸铬纳米簇。接着把乙醇加入该溶液以沉淀出这些纳米簇。接下来,将该沉淀纳米簇干燥以形成蓝色固体,进一步把其磨细为自由流动粉末。由此所获得的纳米簇的原子吸收光谱指示这些纳米簇具有5.85重量%的铬含量。或藉由过滤收集该沉淀物并且接着与甘露醇混合且一起干燥以供进一步配方应用。
亦可将该纳米簇的干燥固体再溶于水中以形成具有强烈激光散射特性的透明溶液,该纳米簇的固态与液态之间有可逆性及好的热稳定性。此溶液尝不出金属味道。
实施例14:苹果酸柠檬酸木糖醇碳酸锌铁铜锰铬纳米簇
配合搅拌将300g的木糖醇、120g的苹果酸、120g的柠檬酸、56g的氯化铁六水合物、34g的氯化铜二水合物、10g的氯化锰四水合物、136g的氯化锌、及0.54g的氯化铬六水合物溶于320g于85℃的水中以制造溶液。藉由添加含有20重量%的碳酸钠的水溶液把该溶液的pH提高至约7。在添加Na2CO3之后的5分钟内,接着获得具有强烈激光散射特性的透明溶液。此强烈的激光散射性质指示形成苹果酸柠檬酸木糖醇碳酸锌铁铜锰铬纳米簇。通过横流隔膜过滤利用分子量截止于3500道尔顿的隔膜从溶剂及自由离子分离出这些纳米簇。分离出来的纳米簇进一步于80℃的烘箱中干燥以形成绿色固体,进一步把其磨细为自由流动粉末。由此所获得的纳米簇的原子吸收光谱指示这些纳米簇具有7.13重量%的锌含量,3.8重量%的铁含量,0.023重量%的铬含量,0.43重量%的锰含量,和2.77重量%的铜含量。
或把乙醇加入该苹果酸柠檬酸木糖醇碳酸锌铁铜锰铬纳米簇溶液以沉淀出这些纳米簇。接下来,藉由过滤收集该沉淀物、干燥并且接着与各种不同配方赋形剂混合,以供进一步配方应用。
亦可将该纳米簇的干燥固体再溶于水中以形成具有强烈激光散射特性的透明溶液,该纳米簇的固态与液态之间有可逆性及好的热稳定性。
其它具体实施例
所有在本说明书中所揭示的特征均可以任何组合合并。在本说明书中所揭示的各特征可为具有相同、等效或类似目的的替代性特征予以取代。因此,除非明确地另行指明,否则所揭示的各特征仅为等效或类似特征的一共通系列的一例子。
从上述说明,本领域技术人员可轻易确定本发明的基本特征,而且可在不会悖离其精神及范围下对本发明进行各种不同变更及修饰使其适于各种不同用法及状况。因此,其它具体实施例也在下列权利要求书的范围以内。
Claims (18)
1.一种组合物,包含:
多个直径介于2nm至500nm且分子量介于3,500至120,000道尔顿的水溶性纳米簇,这些纳米簇各自含有一或多种金属阳离子、一或多种阴离子及一或多种水溶性配体,其中所述一或多种水溶性配体是选自由单糖、加氢单糖、双糖、加氢双糖、寡糖、寡糖衍生物及聚醇所组成的群组,而且所述一或多种金属阳离子、一或多种阴离子及一或多种水溶性配体之间的摩尔比例为1:0.1至9:0.1至10,
其中所述水溶性纳米簇是通过下述方法制备的,包括步骤:
提供含有一或多种水溶性盐类和一或多种水溶性配体的第一透明水溶液,其中该一或多种水溶性盐类包括一或多种金属阳离子;并且该一或多种金属阳离子与该一或多种水溶性配体之间的摩尔比例为1:0.1至10;及
在80-135℃,混合该第一透明水溶液与一或多种阴离子以获得第二透明水溶液,该第二透明水溶液具有介于3.5与11.5之间的pH值,所以形成多个直径介于2nm至500nm的水溶性纳米簇,其各自含有该一或多种金属阳离子、该一或多种阴离子及该一或多种水溶性配体,
其中所述水溶性纳米簇各自含有铁阳离子并且具有15.21-25wt%的铁含量。
2.一种组合物,包含:
多个直径介于2nm至500nm且分子量介于3,500至120,000道尔顿的水溶性纳米簇,这些纳米簇各自含有一或多种金属阳离子、一或多种阴离子及一或多种水溶性配体,
其中所述一或多种金属阳离子是选自由Cr、Al、Bi、Zn、Ba、Cu、Ti、Mg、Mn、Ca、Se、In、Pt及Zr的阳离子所组成的群组;所述一或多种水溶性配体是选自由碳水化合物、碳水化合物衍生物、氨基酸、聚醚、聚醇及多肽所组成的群组;而且所述一或多种金属阳离子、一或多种阴离子及一或多种水溶性配体之间的摩尔比例为1:0.1至9:0.1至10,
其中所述水溶性纳米簇是通过下述方法制备的,包括步骤:
提供含有一或多种水溶性盐类和一或多种水溶性配体的第一透明水溶液,其中该一或多种水溶性盐类包括一或多种金属阳离子;并且该一或多种金属阳离子与该一或多种水溶性配体之间的摩尔比例为1:0.1至10;及
在80-135℃,混合该第一透明水溶液与一或多种阴离子以获得第二透明水溶液,该第二透明水溶液具有介于3.5与11.5之间的pH值,所以形成多个直径介于2nm至500nm的水溶性纳米簇,其各自含有该一或多种金属阳离子、该一或多种阴离子及该一或多种水溶性配体,
其中所述水溶性纳米簇各自含有铬阳离子并且具有5.85-8.09wt%的铬含量。
3.如权利要求1或2的组合物,其中所述一或多种金属阳离子、一或多种阴离子及一或多种水溶性配体之间的摩尔比例为1:0.5至3:1至4。
4.如权利要求1的组合物,其中所述一或多种水溶性配体是选自由木糖醇、异麦芽糖、异麦芽、甘露醇、***糖、山梨醇及果寡糖所组成的群组。
5.如权利要求4的组合物,其中所述一或多种金属阳离子是选自由Fe(II)及Fe(III)所组成的群组;所述一或多种水溶性配体是选自由山梨醇、甘露醇、***糖、木糖醇及异麦芽所组成的群组;及所述一或多种阴离子是选自由碳酸根、重碳酸根、磷酸根、焦磷酸根、苹果酸根、乳酸根、反丁烯二酸根、酒石酸根、丙二酸根、草酸根、丁二酸根、抗坏血酸根、柠檬酸根、葡萄糖酸、甘油磷酸根及氢氧根离子所组成的群组。
6.如权利要求1的组合物,其中所述一或多种金属阳离子是选自由Fe(II)及Fe(III)所组成的群组;所述一或多种水溶性配体为蔗糖;及所述一或多种阴离子是选自由碳酸根、重碳酸根、氢氧根、柠檬酸根、苹果酸根、反丁烯二酸根、酒石酸根、磷酸根、丙二酸根、草酸根、丁二酸根、抗坏血酸根、焦磷酸根、甘油磷酸根、葡萄糖酸根及乳酸根所组成的群组。
7.如权利要求1或2的组合物,其中所述多个纳米簇具有介于10,000至120,000道尔顿的分子量。
8.如权利要求1或2的组合物,其中所述组合物为食品、化妆品或药品。
9.如权利要求8的组合物,其中所述食物为茶、盐、酱、调味剂、饮料、果汁、牛奶、咖啡、果酱、冰淇淋、酵母乳、饼干、糖果、谷物食品、面包、面条、甜甜圈、硬面包圈、巧克力类或点心棒、动植提取物。
10.如权利要求1或2的组合物,其中所述组合物为干燥形态。
11.如权利要求1或2的组合物,其中所述组合物为液态。
12.如权利要求1或2的组合物,其中所述组合物为半固态。
13.如权利要求1的组合物,其中所述组合物为具有3.5至10的pH值的透明水溶液。
14.如权利要求13的组合物,其中所述一或多种金属阳离子是选自由Fe(II)及Fe(III)所组成的群组;所述一或多种水溶性配体是选自由山梨醇、甘露醇、***糖、木糖醇及异麦芽所组成的群组;及所述一或多种阴离子是选自由碳酸根、重碳酸根、磷酸根、焦磷酸根、苹果酸根、反丁烯二酸根、酒石酸根、乳酸根、丙二酸根、草酸根、丁二酸根、抗坏血酸根、葡萄糖酸根、甘油磷酸根及氢氧根离子。
15.如权利要求13的组合物,其中所述一或多种金属阳离子是选自由Fe(II)及Fe(III)所组成的群组;所述一或多种水溶性配体为蔗糖;及所述一或多种阴离子是选自由碳酸根、氢氧根离子、柠檬酸根、苹果酸根、反丁烯二酸根、酒石酸根、草酸根、丁二酸根、抗坏血酸根、葡萄糖酸根、焦磷酸根、甘油磷酸根及乳酸根所组成的群组。
16.如权利要求2的组合物,其中所述一或多种金属阳离子是选自由Mg(II)、Al(III)、Ca(II)、Cr(III)、Cu(II)、Zn(II)、Mn(II)、Ti(IV)所组成的群组。
17.如权利要求16的组合物,其中所述组合物为具有介于3.5与11.5之间的pH值的透明水溶液。
18.一种含铁的组合物,包含:
多个直径介于2nm至500nm且分子量介于3,500至120,000道尔顿的水溶性纳米簇,这些纳米簇各自含有一或多种铁阳离子、一或多种阴离子及一或多种非聚合性水溶性配体,其中所述一或多种非聚合性水溶性配体是选自由木糖醇、甘露醇、***糖、异麦芽糖、异麦芽、山梨醇及果寡糖所组成的群组,而且所述一或多种铁阳离子、一或多种阴离子及一或多种非聚合性水溶性配体之间的摩尔比例为1:0.1至9:0.1至10,其中所述水溶性纳米簇是通过下述方法制备的,包括步骤:
提供含有一或多种水溶性盐类和一或多种水溶性配体的第一透明水溶液,其中该一或多种水溶性盐类包括一或多种金属阳离子;并且该一或多种金属阳离子与该一或多种水溶性配体之间的摩尔比例为1:0.1至10;及
在80-135℃,混合该第一透明水溶液与一或多种阴离子以获得第二透明水溶液,该第二透明水溶液具有介于3.5与11.5之间的pH值,所以形成多个直径介于2nm至500nm的水溶性纳米簇,其各自含有该一或多种金属阳离子、该一或多种阴离子及该一或多种水溶性配体,
其中所述水溶性纳米簇各自具有15.21-25wt%的铁含量。
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CN111568922B (zh) * | 2020-05-09 | 2022-05-03 | 深圳深见医药科技有限公司 | 治疗非典型抗精神病药物引起的不良反应 |
CN112168844A (zh) * | 2020-09-29 | 2021-01-05 | 神奈纳米医药技术(珠海)有限公司 | 一种氢氧化铁碳水化合物复合物的制备方法 |
CN114523120B (zh) * | 2021-12-31 | 2024-03-26 | 华东理工大学 | 一种金属合金纳米簇颗粒的制备方法 |
WO2024100217A1 (fr) * | 2022-11-10 | 2024-05-16 | Université De Lorraine | Nanoclusters à base de zinc, leurs procédés d'obtention et leurs utilisations pour lutter contre les carences en zinc |
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US20120093898A1 (en) | 2012-04-19 |
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CN102451185A (zh) | 2012-05-16 |
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MY165207A (en) | 2018-03-05 |
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