CN114917365B - Wgx50环糊精包合物、制备方法、溶解度及环糊精包裹率测定方法 - Google Patents
Wgx50环糊精包合物、制备方法、溶解度及环糊精包裹率测定方法 Download PDFInfo
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- CN114917365B CN114917365B CN202210653695.8A CN202210653695A CN114917365B CN 114917365 B CN114917365 B CN 114917365B CN 202210653695 A CN202210653695 A CN 202210653695A CN 114917365 B CN114917365 B CN 114917365B
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- APEJMQOBVMLION-VOTSOKGWSA-N trans-cinnamamide Chemical compound NC(=O)\C=C\C1=CC=CC=C1 APEJMQOBVMLION-VOTSOKGWSA-N 0.000 description 1
- 230000002087 whitening effect Effects 0.000 description 1
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/69—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
- A61K47/6949—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes
- A61K47/6951—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes using cyclodextrin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
- A61K8/42—Amides
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
- A61K8/73—Polysaccharides
- A61K8/738—Cyclodextrins
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
- G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
- G01N21/31—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
- G01N21/33—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using ultraviolet light
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N5/00—Analysing materials by weighing, e.g. weighing small particles separated from a gas or liquid
- G01N5/04—Analysing materials by weighing, e.g. weighing small particles separated from a gas or liquid by removing a component, e.g. by evaporation, and weighing the remainder
Abstract
本发明公开了一种WGX50环糊精包合物、制备方法、溶解度及环糊精包裹率测定方法,WGX50环糊精包合物所使用的环糊精为β‑环糊精或羟丙基‑γ‑环糊精,WGX50与环糊精的投料摩尔比为0.5:1~2:1;采用共沉淀法、共蒸发法或干法捏合法将WGX50与环糊精制成WGX50环糊精包合物。本发明利用环糊精及其衍生物分子具有疏水空腔的结构特点,通过合适的工艺条件筛选制备稳定的WGX50环糊精包合物,其可有效改善WGX50在水中的溶解度,为WGX50在化妆品及医药领域的应用奠定基础。
Description
技术领域
本发明涉及化妆品及医药技术领域,具体涉及一种WGX50环糊精包合物、制备方法、溶解度及环糊精包裹率测定方法。
背景技术
环糊精(cyclodextrin,简称CD)是淀粉用嗜碱性芽孢杆菌产生的环糊精葡萄糖转位酶作用后形成的产物,其是由6~15个D-葡萄糖分子以1,4-糖苷键连接的环状低聚糖化合物;最常见的环糊精α-CD、β-CD和γ-CD,分别由6个、7个和8个葡萄糖单元组成。随着应用的深入,不断有新的环糊精衍生物被开发出来,如羟丙基化环糊精、双甲基化环糊精和葡萄糖环糊精等,以期获得更加理想的性能。环糊精及其衍生物均具有一个由亲水的外表面和相对疏水的中心空腔构成的截头圆锥形体结构,这种独特的结构特性使CDs能够通过非共价力与难溶于水的脂溶性化合物相互作用,将后者包合在空腔中,从而提高脂溶性物质在水中的溶解度,同时具有增加被包合物稳定性和促渗的作用。环糊精包合物已经成为医药领域应用十分广泛的递送系统,在化妆品领域的应用也日趋深入。
WGX50化学名称N-(3,4-二甲氧基苯乙基)肉桂酰胺,是天然存在于花椒中的活性成分,具有显著的抗氧化和清除自由基的能力,有望作为抗衰老或美白类化妆品的原料。此外魏冬青等人的研究还表明,WGX50可以通过激动α-7乙酰胆碱能受体及解聚β-amyloid等途径,有效地治疗由β-amyloid诱导的老年痴呆症,具有较大的临床应用价值。但WGX50存在溶解性差和水溶性低的缺点,导致其实际应用受限。
发明内容
针对现有技术中WGX50水溶性差的问题,本发明利用环糊精及其衍生物对脂溶性物质的包合性能,而提供一种可改善WGX50水溶性的WGX50环糊精包合物、制备方法、溶解度及环糊精包裹率测定方法,提高WGX50实际应用潜能。
本发明第一目的在于提供一种WGX50环糊精包合物,所述WGX50环糊精包合物所使用的原料为WGX50和环糊精,环糊精为β-环糊精(β-CD)或羟丙基-γ-环糊精(HP-γ-CD),WGX50与环糊精的投料摩尔比为0.5:1~2:1。
本发明第二目的在于提供一种WGX50环糊精包合物的制备方法,包括:
按预设的摩尔比称取WGX50与环糊精,即WGX50与环糊精的投料摩尔比为0.5:1~2:1;采用共沉淀法、共蒸发法或干法捏合法将WGX50与环糊精制成WGX50环糊精包合物。
作为本发明的进一步改进,采用共沉淀法制备WGX50环糊精包合物的方法,包括:
S11、将WGX50溶于无水乙醇中,制得WGX50乙醇溶液;其中,
无水乙醇的用量为保证WGX50充分溶解的最小用量;
S12、将环糊精溶于去离子水中,搅拌加热至预设温度至其完全溶解,制得环糊精水溶液;其中,
去离子水的用量为环糊精质量的20~30倍,搅拌加热的温度为40-70℃,优选为50-60℃;
S13、将WGX50乙醇溶液缓慢加入环糊精水溶液中,保温搅拌预设时间后,静置、抽滤,得到滤饼;其中,
保温搅拌的时间为3~12h,优选为4-8h,静置条件为4℃放置24h;
S14、将滤饼用少量无水乙醇洗涤两次、室温真空干燥至恒重,得到WGX50环糊精包合物。
作为本发明的进一步改进,采用共蒸发法制备WGX50环糊精包合物的方法,包括:
S21、将WGX50溶于无水乙醇中,制得WGX50乙醇溶液;其中,
无水乙醇的用量为WGX50质量的20~30倍,优选为20倍;
S22、将环糊精溶于去离子水中,制得环糊精水溶液;其中,
去离子水的用量为环糊精质量的20~30倍,优选为20倍;
S23、将WGX50乙醇溶液与环糊精水溶液混合预设时间后,减压蒸发除去溶剂,得到WGX50环糊精包合物;其中,
WGX50乙醇溶液与环糊精水溶液的混合时间为24h-96h,优选为36h-72h,混合方式为搅拌混合或振荡混合。
作为本发明的进一步改进,采用干法捏合法制备WGX50环糊精包合物的方法,包括:
S31、将WGX50溶于无水乙醇中,制得WGX50乙醇溶液;其中,
无水乙醇的用量为WGX50质量的20~30倍,优选为20倍;
S32、将环糊精溶于去离子水中,制得环糊精水溶液;其中,
去离子水的用量为环糊精质量的5~10倍,优选为5倍;
S33、将WGX50乙醇溶液逐滴加入到环糊精水溶液中,边加边研磨,滴加完毕后,继续研磨预设时间,而后烘干,得到WGX50环糊精包合物;其中,
滴加完成后继续研磨20~40min,优选Wie30min,烘干温度为60℃。
本发明的第三目的在于提供一种WGX50环糊精包合物中WGX50的溶解度测定方法,包括:
在水中加入过量的洗涤后的WGX50环糊精包合物,在室温条件下超声处理预设时间后滤膜过滤,滤液用乙醇稀释到预设浓度,在280nm处测定吸光度,根据WGX50紫外吸收光谱标准工作曲线,计算WGX50含量,即得经包合后WGX50的溶解度。
本发明的第四目的在于提供一种WGX50环糊精包合物的包裹率测定方法,包括:
将WGX50环糊精包合物分为两份;一份溶于乙醇溶液,经超声处理、离心后,收集上清液;用乙醇稀释后,测量其在280nm处的吸光度,根据标准曲线计算WGX50的质量,即为包合物中WGX50的总质量;另一份加入无水乙醇中充分混匀,离心除去上清液,将样品放于烘箱中挥去无水乙醇;按包合物中WGX50的总质量的测定步骤测定此样品中的WGX50质量,即被包合的WGX50的质量;基于被包合的WGX50的质量与包合物中WGX50的总质量的比值,计算包合率。
与现有技术相比,本发明的有益效果为:
本发明利用环糊精及其衍生物分子具有疏水空腔的结构特点,通过合适的工艺条件筛选制备稳定的WGX50环糊精包合物,其可有效改善WGX50在水中的溶解度,为WGX50在化妆品及医药领域的应用奠定基础。
附图说明
图1为β-环糊精的扫描电镜图;
图2为WGX50的扫描电镜图;
图3为β-环糊精与WGX50的质量比为100:1时混合物的扫描电镜图;
图4为包合物3的扫描电镜图;
图5为包合物17的扫描电镜图。
图6为包合物20的扫描电镜图。
具体实施方式
为使本发明实施例的目的、技术方案和优点更加清楚,下面将结合本发明实施例中的附图,对本发明实施例中的技术方案进行清楚、完整地描述,显然,所描述的实施例是本发明的一部分实施例,而不是全部的实施例。基于本发明中的实施例,本领域普通技术人员在没有做出创造性劳动的前提下所获得的所有其他实施例,都属于本发明保护的范围。
下面结合附图对本发明做进一步的详细描述:
实施例一:
WGX50/β-CD包合物1,白色粉末;
制备条件:1:2摩尔比投料,共沉淀法,60℃搅拌蒸发乙醇;
制备方法:准确称量908mgβ-环糊精溶解分散于20mL去离子水,498mg WGX50溶于5mL无水乙醇,环糊精水溶液搅拌加热至60℃,待其完全溶解后,缓慢加入WGX50乙醇溶液,保温60℃搅拌4h后,4℃放置24h后,抽滤,滤饼用少量无水乙醇洗涤两次,室温真空干燥至恒重,即得粉末状固体包合物1。
实施例二:
WGX50/β-CD包合物2,白色粉末;
制备条件:1:1.5摩尔比投料,共沉淀法,60℃搅拌蒸发乙醇;
制备方法:准确称量908mgβ-环糊精溶解分散于20mL去离子水,373mg WGX50溶于5mL无水乙醇,环糊精水溶液搅拌加热至60℃,待其完全溶解后,缓慢加入WGX50乙醇溶液,保温60℃搅拌4h后,4℃放置24h后,抽滤,滤饼用少量无水乙醇洗涤两次,室温真空干燥至恒重,即得粉末状固体包合物2。
实施例三:
WGX50/β-CD包合物3,白色粉末;
制备条件:1:1摩尔比投料,共沉淀法,60℃搅拌蒸发乙醇;
制备方法:准确称量908mgβ-环糊精溶解分散于20mL去离子水,249mg WGX50溶于5mL无水乙醇,环糊精水溶液搅拌加热至60℃,待其完全溶解后,缓慢加入WGX50乙醇溶液,保温60℃搅拌4h后,4℃放置24h后,抽滤,滤饼用少量无水乙醇洗涤两次,室温真空干燥至恒重,即得粉末状固体包合物3,其扫描电镜图如图4所示。
实施例四:
WGX50/β-CD包合物4,白色粉末;
制备条件:1.5:1摩尔比投料,共沉淀法,60℃搅拌蒸发乙醇;
制备方法:准确称量908mgβ-环糊精溶解分散于20mL去离子水,166mg WGX50溶于5mL无水乙醇,环糊精水溶液搅拌加热至60℃,待其完全溶解后,缓慢加入WGX50乙醇溶液,保温60℃搅拌4h后,4℃放置24h后,抽滤,滤饼用少量无水乙醇洗涤两次,室温真空干燥至恒重,即得粉末状固体包合物4。
实施例五:
WGX50/β-CD包合物5,白色粉末;
制备条件:2:1摩尔比投料,共沉淀法,60℃搅拌蒸发乙醇;
制备方法:准确称量908mgβ-环糊精溶解分散于20mL去离子水,125mg WGX50溶于5mL无水乙醇,环糊精水溶液搅拌加热至60℃,待其完全溶解后,缓慢加入WGX50乙醇溶液,保温60℃搅拌4h后,4℃放置24h后,抽滤,滤饼用少量无水乙醇洗涤两次,室温真空干燥至恒重,即得粉末状固体包合物5。
其中,实施例一~实施例五为共沉淀法下的WGX50/β-CD不同投料比的对比。
实施例六:
WGX50/HP-γ-CD包合物6,白色粉末状固体;
制备条件:1:1摩尔比投料,共沉淀法,60℃搅拌蒸发乙醇;
制备方法:准确称量1.409g HP-γ-CD溶解分散于20mL去离子水,249mg WGX50溶于5mL无水乙醇,环糊精水溶液搅拌加热至60℃,待其完全溶解后,缓慢加入WGX50乙醇溶液,保温60℃搅拌4h后,4℃放置24h后,抽滤,滤饼用少量无水乙醇洗涤两次,室温真空干燥至恒重,即得白色粉末状固体包合物6。
其中,实施例六与实施例三为共沉淀法下不同种类环糊精对比。
实施例七:
WGX50/β-CD包合物7,白色粉末;
制备条件:1:1摩尔比投料,共沉淀法,40℃搅拌蒸发乙醇;
制备方法:准确称量908mgβ-环糊精溶解分散于20mL去离子水,249mg WGX50溶于5mL无水乙醇,环糊精水溶液搅拌加热至40℃,待其完全溶解后,缓慢加入WGX50乙醇溶液,保温60℃搅拌4h后,4℃放置24h后,抽滤,滤饼用少量无水乙醇洗涤两次,室温真空干燥至恒重,即得粉末状固体包合物7。
实施例八:
WGX50/β-CD包合物8,白色粉末;
制备条件:1:1摩尔比投料,共沉淀法,70℃搅拌蒸发乙醇;
制备方法:准确称量908mgβ-环糊精溶解分散于20mL去离子水,249mg WGX50溶于5mL无水乙醇,环糊精水溶液搅拌加热至70℃,待其完全溶解后,缓慢加入WGX50乙醇溶液,保温60℃搅拌4h后,4℃放置24h后,抽滤,滤饼用少量无水乙醇洗涤两次,室温真空干燥至恒重,即得粉末状固体包合物8。
其中,实施例七~实施例八与实施例三为共沉淀法下不同保温温度对比。
实施例九:
WGX50/β-CD包合物9,白色粉末;
制备条件:1:1摩尔比投料,共沉淀法,60℃搅拌蒸发乙醇;
制备方法:准确称量908mgβ-环糊精溶解分散于20mL去离子水,249mg WGX50溶于5mL无水乙醇,环糊精水溶液搅拌加热至60℃,待其完全溶解后,缓慢加入WGX50乙醇溶液,保温60℃搅拌3h后,4℃放置24h后,抽滤,滤饼用少量无水乙醇洗涤两次,室温真空干燥至恒重,即得粉末状固体包合物9。
实施例十:
WGX50/β-CD包合物10,白色粉末;
制备条件:1:1摩尔比投料,共沉淀法,60℃搅拌蒸发乙醇;
制备方法:准确称量908mgβ-环糊精溶解分散于20mL去离子水,249mg WGX50溶于5mL无水乙醇,环糊精水溶液搅拌加热至60℃,待其完全溶解后,缓慢加入WGX50乙醇溶液,保温60℃搅拌8h后,4℃放置24h后,抽滤,滤饼用少量无水乙醇洗涤两次,室温真空干燥至恒重,即得粉末状固体包合物10。
实施例十一:
WGX50/β-CD包合物11,白色粉末;
制备条件:1:1摩尔比投料,共沉淀法,60℃搅拌蒸发乙醇;
制备方法:准确称量908mgβ-环糊精溶解分散于20mL去离子水,249mg WGX50溶于5mL无水乙醇,环糊精水溶液搅拌加热至60℃,待其完全溶解后,缓慢加入WGX50乙醇溶液,保温60℃搅拌12h后,4℃放置24h后,抽滤,滤饼用少量无水乙醇洗涤两次,室温真空干燥至恒重,即得粉末状固体包合物11。
其中,实施例九~实施例十一与实施例三为共沉淀法下不同保温时间对比。
实施例十二:
WGX50/β-CD包合物12,白色粉末;
制备条件:1:1摩尔比投料,共沉淀法,60℃搅拌蒸发乙醇;
制备方法:准确称量908mgβ-环糊精溶解分散于18mL去离子水,249mg WGX50溶于5mL无水乙醇,环糊精水溶液搅拌加热至60℃,待其完全溶解后,缓慢加入WGX50乙醇溶液,保温60℃搅拌4h后,4℃放置24h后,抽滤,滤饼用少量无水乙醇洗涤两次,室温真空干燥至恒重,即得粉末状固体包合物12。
实施例十三:
WGX50/β-CD包合物13,白色粉末;
制备条件:1:1摩尔比投料,共沉淀法,60℃搅拌蒸发乙醇;
制备方法:准确称量908mgβ-环糊精溶解分散于22mL去离子水,249mg WGX50溶于5mL无水乙醇,环糊精水溶液搅拌加热至60℃,待其完全溶解后,缓慢加入WGX50乙醇溶液,保温60℃搅拌4h后,4℃放置24h后,抽滤,滤饼用少量无水乙醇洗涤两次,室温真空干燥至恒重,即得粉末状固体包合物13。
实施例十四:
WGX50/β-CD包合物14,白色粉末;
制备条件:1:1摩尔比投料,共沉淀法,60℃搅拌蒸发乙醇;
制备方法:准确称量908mgβ-环糊精溶解分散于27mL去离子水,249mg WGX50溶于5mL无水乙醇,环糊精水溶液搅拌加热至60℃,待其完全溶解后,缓慢加入WGX50乙醇溶液,保温60℃搅拌4h后,4℃放置24h后,抽滤,滤饼用少量无水乙醇洗涤两次,室温真空干燥至恒重,即得粉末状固体包合物14。
其中,实施例十二~实施例十四与实施例三为共沉淀法下不同去离子水用量对比。
实施例十五:
WGX50/β-CD包合物15,白色粉末;
制备条件:1:1摩尔比投料,共沉淀法,60℃搅拌蒸发乙醇;
制备方法:准确称量908mgβ-环糊精溶解分散于20mL去离子水,249mg WGX50溶于3mL无水乙醇,环糊精水溶液搅拌加热至60℃,待其完全溶解后,缓慢加入WGX50乙醇溶液,保温60℃搅拌4h后,4℃放置24h后,抽滤,滤饼用少量无水乙醇洗涤两次,室温真空干燥至恒重,即得粉末状固体包合物15。
实施例十六:
WGX50/β-CD包合物16,白色粉末;
制备条件:1:1摩尔比投料,共沉淀法,60℃搅拌蒸发乙醇;
制备方法:准确称量908mgβ-环糊精溶解分散于20mL去离子水,249mg WGX50溶于6.3mL无水乙醇,环糊精水溶液搅拌加热至60℃,待其完全溶解后,缓慢加入WGX50乙醇溶液,保温60℃搅拌4h后,4℃放置24h后,抽滤,滤饼用少量无水乙醇洗涤两次,室温真空干燥至恒重,即得粉末状固体包合物16。
其中,实施例十五~实施例十六与实施例三为共沉淀法下不同无水乙醇用量对比。
实施例十七:
WGX50/β-CD包合物17,白色粉末;
制备条件:1:1摩尔比投料,共蒸发法,搅拌;
制备方法:准确称量908mgβ-环糊精溶解分散于18mL去离子水,249mg WGX50分散于5mL无水乙醇中,两者混合后,继续室温搅拌24h,60℃旋转蒸发完全除去溶剂,恒温箱干燥至恒重,即得固体包合物17,固体包合物17的扫描电镜图如图5所示。
实施例十八:
WGX50/β-CD包合物18,白色粉末;
制备条件:1:1摩尔比投料,共蒸发法,恒温振荡;
制备方法:准确称量908mgβ-环糊精溶解分散于18mL去离子水,249mg WGX50分散于5mL无水乙醇中,两者混合后,置于恒温培养箱中振荡72h,60℃旋转蒸发完全除去溶剂,恒温箱干燥至恒重,即得固体包合物18。
其中,实施例十七~实施例十八与实施例三为不同混合方式对比。
实施例十九:
WGX50/HP-γ-CD包合物19,白色粉末;
制备条件:1:1摩尔比投料,捏合法;
制备方法:准确称量1.409g HP-γ-环糊精溶解分散于7mL去离子水,249mg WGX50分散于5mL无水乙醇中。将WGX 50乙醇溶液分批加入到环糊精粘稠液中,边加边研磨,滴加完毕后,继续研磨30min,60℃烘箱中干燥至恒重得固体包合物19。
实施例二十:
WGX50/β-CD包合物20,白色粉末;
制备条件:1:1摩尔比投料,捏合法;
制备方法:准确称量908mgβ-环糊精溶解分散于4.5mL去离子水,249mg WGX50分散于5mL无水乙醇中。将WGX 50乙醇溶液分批加入到环糊精粘稠液中,边加边研磨,滴加完毕后,继续研磨30min,60℃烘箱中干燥至恒重得固体包合物20,固体包合物20的扫描电镜图如图6所示。
其中,实施例十九~实施例二十与实施例三为不同混合方式对比。
为说明制备工艺的必要性和先进性,进行了如下的对比例实验。
对比例一:
WGX50/γ-CD包合物21,白色粉末;
制备条件:1:1摩尔比投料,共沉淀法,60℃搅拌蒸发乙醇;
制备方法:准确称量1.038gγ-环糊精溶解分散于20mL去离子水,249mg WGX50溶于5mL无水乙醇,环糊精水溶液搅拌加热至60℃,待其完全溶解后,缓慢加入WGX50乙醇溶液,保温60℃搅拌4h后,4℃放置24h后,抽滤,滤饼用少量无水乙醇洗涤两次,室温真空干燥至恒重,即得粉末状固体包合物21。
对比例二:
WGX50/β-CD包合物22,白色粉末;
制备条件:3:1摩尔比投料,共沉淀法,60℃搅拌蒸发乙醇;
制备方法:准确称量908gβ-环糊精溶解分散于20mL去离子水,934mg WGX50溶于5mL无水乙醇,环糊精水溶液搅拌加热至60℃,待其完全溶解后,缓慢加入WGX50乙醇溶液,保温60℃搅拌4h后,4℃放置24h后,抽滤,滤饼用少量无水乙醇洗涤两次,室温真空干燥至恒重,即得粉末状固体包合物22。
对比例三:
WGX50/β-CD包合物23,白色粉末;
制备条件:1:3摩尔比投料,共沉淀法,60℃搅拌蒸发乙醇;
制备方法:准确称量908mgβ-环糊精溶解分散于20mL去离子水,83mg WGX50溶于5mL无水乙醇,环糊精水溶液搅拌加热至60℃,待其完全溶解后,缓慢加入WGX50乙醇溶液,保温60℃搅拌4h后,4℃放置24h后,抽滤,滤饼用少量无水乙醇洗涤两次,室温真空干燥至恒重,即得粉末状固体包合物23。
对比例四:
WGX50/β-CD包合物24,白色粉末;
制备条件:1:1摩尔比投料,共沉淀法,室温搅拌;
制备方法:准确称量908mgβ-环糊精溶解分散于20mL去离子水,249mg WGX50溶于5mL无水乙醇。向环糊精水溶液中缓慢加入WGX50乙醇溶液,室温搅拌4h后,4℃放置24h后,抽滤,滤饼用少量无水乙醇洗涤两次,室温真空干燥至恒重,即得粉末状固体包合物24。
对比例五:
WGX50/β-CD包合物25,白色粉末;
制备条件:1:1摩尔比投料,共沉淀法,80℃搅拌蒸发乙醇;
制备方法:准确称量908mgβ-环糊精溶解分散于20mL去离子水,249mg WGX50溶于5mL无水乙醇,环糊精水溶液搅拌加热至80℃,待其完全溶解后,缓慢加入WGX50乙醇溶液,保温80℃搅拌4h后,4℃放置24h后,抽滤,滤饼用少量无水乙醇洗涤两次,室温真空干燥至恒重,即得粉末状固体包合物25。
对比例六:
WGX50/β-CD包合物26,白色粉末;
制备条件:1:1摩尔比投料,共沉淀法,60℃搅拌蒸发乙醇,搅拌2h;
制备方法:准确称量908mgβ-环糊精溶解分散于20mL去离子水,249mg WGX50溶于5mL无水乙醇,环糊精水溶液搅拌加热至60℃,待其完全溶解后,缓慢加入WGX50乙醇溶液,保温60℃搅拌2h后,4℃放置24h后,抽滤,滤饼用少量无水乙醇洗涤两次,室温真空干燥至恒重,即得粉末状固体包合物26。
对比例七:
WGX50/β-CD包合物27,白色粉末;
制备条件:1:1摩尔比投料,共沉淀法,60℃搅拌蒸发乙醇,保温时间16h;
制备方法:准确称量908mgβ-环糊精溶解分散于20mL去离子水,249mg WGX50溶于5mL无水乙醇,环糊精水溶液搅拌加热至60℃,待其完全溶解后,缓慢加入WGX50乙醇溶液,保温60℃搅拌16h后,4℃放置24h后,抽滤,滤饼用少量无水乙醇洗涤两次,室温真空干燥至恒重,即得粉末状固体包合物27。
对比例八:
WGX50/β-CD包合物28,白色粉末;
制备条件:1:1摩尔比投料,共沉淀法,60℃搅拌蒸发乙醇,去离子水10倍用量;
制备方法:准确称量908mgβ-环糊精溶解分散于10mL去离子水,249mg WGX50溶于5mL无水乙醇,环糊精水溶液搅拌加热至60℃,完全分散均匀后,缓慢加入WGX50乙醇溶液,保温60℃搅拌4h后,4℃放置24h后,抽滤,滤饼用少量无水乙醇洗涤两次,室温真空干燥至恒重,即得粉末状固体包合物28。
对比例九:
WGX50/β-CD包合物29,白色粉末;
制备条件:1:1摩尔比投料,共沉淀法,60℃搅拌蒸发乙醇,去离子水50倍用量;
制备方法:准确称量908mgβ-环糊精溶解分散于45mL去离子水,249mg WGX50溶于5mL无水乙醇,环糊精水溶液搅拌加热至60℃完全溶解后,缓慢加入WGX50乙醇溶液,保温60℃搅拌4h后,4℃放置24h后,抽滤,滤饼用少量无水乙醇洗涤两次,室温真空干燥至恒重,即得粉末状固体包合物29。
对比例十:
WGX50/β-CD包合物30,白色粉末;
制备条件:1:1摩尔比投料,共蒸发法,混合12h;
制备方法:准确称量908mgβ-环糊精溶解分散于18mL去离子水,249mg WGX50分散于5mL无水乙醇中,两者混合后,置于恒温培养箱中振荡12h,60℃旋转蒸发完全除去溶剂,恒温箱干燥至恒重,即得固体包合物30。
对比例十一:
WGX50/β-CD包合物31,白色粉末;
制备条件:1:1摩尔比投料,共蒸发法,混合120h;
制备方法:准确称量908mgβ-环糊精溶解分散于18mL去离子水,249mg WGX50分散于5mL无水乙醇中,两者混合后,置于恒温培养箱中振荡120h,60℃旋转蒸发完全除去溶剂,恒温箱干燥至恒重,即得固体包合物31。
实验:
WGX50水中溶解度的测定
在1mL水中加入过量WGX50,在室温条件下(25℃)超声处理20min后0.45μm滤膜过滤,滤液用乙醇稀释到合适浓度,在280nm处测定吸光度,根据WGX50紫外吸收光谱标准工作曲线,计算WGX50含量,即为其在水中的饱和溶解度。
WGX50/CD包合物中WGX50溶解度的测定
将获得的固体包合物粉末用无水烯醇漂洗三次后烘干待用。在1mL水中加入过量的洗涤后的固体包合物,在室温条件下(25℃)超声处理5min后0.45μm滤膜过滤,滤液用乙醇稀释到合适浓度,在280nm处测定吸光度,根据WGX50紫外吸收光谱标准工作曲线,计算WGX50含量,即得经包合后WGX50的溶解度。
WGX50/CD包合物包合率的测定
称取10mg固体包合物,共两份。其中一份溶于乙醇溶液,在25℃超声处理20min,以10000r/min离心5min,收集上清液;用90%乙醇适当稀释,测量其在280nm处的吸光度,根据标准曲线计算WGX50的质量,即为包合物中WGX50的总质量。另一份加入1mL无水乙醇,充分混匀,离心除去上清液(用以洗去未被包合的WGX50),重复洗两次;将样品放于烘箱中挥去无水乙醇;按上述包合物样品中WGX50总质量的测定步骤测定此样品中的WGX50质量,即被包合的WGX50的质量;基于被包合的WGX50的质量与包合物中WGX50的总质量的比值,计算包合率。
通过上述测定可得如表1所示数据。
表1
结论:
WGX50的饱和溶解度为0.013mg/mL,为难溶物质;经过环糊精包裹后,其在水中溶解度均有明显的升高,不同工艺制备的包合物包裹率和溶解度改善情况略有不同;从本实验可以看出,共蒸发法的包合效果>共沉淀法>>捏合法;原因在于:其与包合温度和形成包合物时的溶液介质性质有关。
相比于捏合法,共蒸发法和共沉淀法均有高于室温下的混合时间,稳定高,分子的热运动加速,可能有利于WGX50向环糊精内腔中的迁移;而与共沉淀法相比,高温蒸发的过程,乙醇的浓度逐渐减小,溶液更加亲水性,而水溶性差的WGX50则更倾向于向疏水性的环糊精内腔移动,从而提高包合效率。
将实施例3与对比例1相比较,可以看出γ-环糊精对WGX50的包合效果较差,包裹率仅有23.46%,原因在于:由于γ-环糊精的空腔尺寸与WGX50分子大小不匹配,无法形成稳定的包合物。
将实施例3与对比例2、3相比较,可以看出WGX50和β-环糊精的比例要适当(0.5:1~2:1),继续降低β-环糊精的用量,可能会导致无法将所有的WGX50进行有效包合;而增加β-环糊精的用量,包裹率随之上升,但3:1与2:1的效果相当,因此从经济角度出发,不易过量使用β-环糊精。
共沉淀工艺中,适宜的温度也是获得理想包合效果的关键,温度过低,如室温,无水乙醇难以挥发,导致WGX50在混合液中的溶解度较大,导致包合过程缺乏动力;而过高的包合温度对包合作用也是不利的,可能是由于分子的热运动加快,影响了WGX50的包合与游离的动态平衡。
共沉淀法中去离子水和无水乙醇主要起到溶解环糊精和WGX50的作用,使两者能够以游离的分子状态充分接触,并为包合作用的发生提供适宜的介质场所,因此两者的比例也会影响包合效果(对比例4和5)。
适宜的包合时间对共沉淀法和共蒸发法都是至关重要的,时间过短,无法获得理想的包合效果,但时间过长,包裹率也不再呈现明显增加的趋势(对比例6和7,对比例10和11)。
去离子水用量过低,环糊精无法完全溶解,与WGX50不能充分接触并作用,导致包合不充分,降低包裹率及其包合物的溶解度。而去离子水用量过高,导致包合物不能很好地从溶液中析出,包合物总收率低(对比例8和9)。
最后,选取部分包合物采用扫描电镜对其进行了形貌进行了表征,如图1~6;从图中可以看出,β-环糊精的形貌为不规则球形,如图1所示;WGX50为片层状,如图2所示;而包合物的结构均不同于两者,基本为棒状结构,如图4~6所示;对比两者物理混合物(图3所示)及三种不同工艺制备的包合物形貌可以初步确定包合物的形成。
以上仅为本发明的优选实施例而已,并不用于限制本发明,对于本领域的技术人员来说,本发明可以有各种更改和变化。凡在本发明的精神和原则之内,所作的任何修改、等同替换、改进等,均应包含在本发明的保护范围之内。
Claims (1)
1.一种WGX50环糊精包合物的制备方法,其特征在于,包括:
按预设的摩尔比称取WGX50与环糊精,环糊精为β-环糊精,WGX50与环糊精的投料摩尔比为0.5:1~2:1;采用共沉淀法或共蒸发法将WGX50与环糊精制成WGX50环糊精包合物;
其中,
采用共沉淀法制备WGX50环糊精包合物的方法,包括:
将WGX50溶于无水乙醇中,制得WGX50乙醇溶液;其中,所述无水乙醇的用量为保证WGX50充分溶解的最小用量;
将环糊精溶于去离子水中,搅拌加热至预设温度至其完全溶解,制得环糊精水溶液;其中,所述去离子水的用量为环糊精质量的20~30倍;
将WGX50乙醇溶液加入环糊精水溶液中,保温搅拌预设时间后,静置、抽滤,得到滤饼;其中,搅拌加热的温度为40-70℃,保温搅拌的时间为3~12h,静置条件为4℃放置24h;
将滤饼进行洗涤、真空干燥,得到WGX50环糊精包合物;
采用共蒸发法制备WGX50环糊精包合物的方法,包括:
将WGX50溶于无水乙醇中,制得WGX50乙醇溶液;其中,所述无水乙醇的用量为WGX50质量的20~30倍;
将环糊精溶于去离子水中,制得环糊精水溶液;其中,所述去离子水的用量为环糊精质量的20~30倍;
将WGX50乙醇溶液与环糊精水溶液混合预设时间后,减压蒸发除去溶剂,得到WGX50环糊精包合物;其中,所述WGX50乙醇溶液与环糊精水溶液的混合时间为24h-96h,混合方式为搅拌混合或振荡混合。
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