CN113912854B - 一种具有pH响应的两亲性聚戊烯醇多孔衍生物的制备方法 - Google Patents

一种具有pH响应的两亲性聚戊烯醇多孔衍生物的制备方法 Download PDF

Info

Publication number
CN113912854B
CN113912854B CN202111365445.6A CN202111365445A CN113912854B CN 113912854 B CN113912854 B CN 113912854B CN 202111365445 A CN202111365445 A CN 202111365445A CN 113912854 B CN113912854 B CN 113912854B
Authority
CN
China
Prior art keywords
polyprenol
derivative
amphiphilic
porous
response
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
CN202111365445.6A
Other languages
English (en)
Other versions
CN113912854A (zh
Inventor
王成章
袁花
张昌伟
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Institute of Chemical Industry of Forest Products of CAF
Original Assignee
Institute of Chemical Industry of Forest Products of CAF
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Institute of Chemical Industry of Forest Products of CAF filed Critical Institute of Chemical Industry of Forest Products of CAF
Priority to CN202111365445.6A priority Critical patent/CN113912854B/zh
Publication of CN113912854A publication Critical patent/CN113912854A/zh
Application granted granted Critical
Publication of CN113912854B publication Critical patent/CN113912854B/zh
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G81/00—Macromolecular compounds obtained by interreacting polymers in the absence of monomers, e.g. block polymers
    • C08G81/02—Macromolecular compounds obtained by interreacting polymers in the absence of monomers, e.g. block polymers at least one of the polymers being obtained by reactions involving only carbon-to-carbon unsaturated bonds
    • C08G81/024—Block or graft polymers containing sequences of polymers of C08C or C08F and of polymers of C08G
    • C08G81/028—Block or graft polymers containing sequences of polymers of C08C or C08F and of polymers of C08G containing polyamide sequences
    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
    • A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
    • A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
    • 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
    • A61K31/74—Synthetic polymeric materials
    • A61K31/765—Polymers containing oxygen
    • 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
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
    • 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
    • A61K47/51—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 non-active ingredient being a modifying agent
    • A61K47/56—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 non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
    • A61K47/59—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 non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
    • A61K47/60—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 non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
    • C08F8/00—Chemical modification by after-treatment
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G81/00—Macromolecular compounds obtained by interreacting polymers in the absence of monomers, e.g. block polymers
    • C08G81/02—Macromolecular compounds obtained by interreacting polymers in the absence of monomers, e.g. block polymers at least one of the polymers being obtained by reactions involving only carbon-to-carbon unsaturated bonds
    • C08G81/024—Block or graft polymers containing sequences of polymers of C08C or C08F and of polymers of C08G
    • C08G81/025—Block or graft polymers containing sequences of polymers of C08C or C08F and of polymers of C08G containing polyether sequences
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J9/00—Working-up of macromolecular substances to porous or cellular articles or materials; After-treatment thereof
    • C08J9/28—Working-up of macromolecular substances to porous or cellular articles or materials; After-treatment thereof by elimination of a liquid phase from a macromolecular composition or article, e.g. drying of coagulum
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J2201/00—Foams characterised by the foaming process
    • C08J2201/04—Foams characterised by the foaming process characterised by the elimination of a liquid or solid component, e.g. precipitation, leaching out, evaporation
    • C08J2201/048—Elimination of a frozen liquid phase
    • C08J2201/0482—Elimination of a frozen liquid phase the liquid phase being organic
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J2387/00—Characterised by the use of unspecified macromolecular compounds, obtained otherwise than by polymerisation reactions only involving unsaturated carbon-to-carbon bonds
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Abstract

本发明公开了一种具有pH响应的两亲性聚戊烯醇多孔衍生物的制备方法，该方法包括(1)炔基化聚戊烯醇的制备：在碱催化条件下，将聚戊烯醇与溴丙炔反应，得到炔基化聚戊烯醇；(2)亲水性聚戊烯醇的制备：炔基化聚戊烯醇与亲水性叠氮试剂进行点击反应，得到亲水性聚乙二醇化聚戊烯醇；(3)pH响应两亲性聚戊烯醇多孔衍生物的制备：在羧基活化剂存在下，将r‑聚谷氨酸与亲水性聚戊烯醇进行偶联反应，得到具有pH响应的两亲性聚戊烯醇多孔衍生物。该衍生物具有多孔特性使其对阿霉素有较高的装载率，同时对不同的pH有优良的响应性，可用于药物装载材料使用。

Description

一种具有pH响应的两亲性聚戊烯醇多孔衍生物的制备方法
技术领域
本发明涉及一种具有pH响应的两亲性聚戊烯醇多孔衍生物的制备方法，具体是指以聚戊烯醇、溴丙炔为原料，在碱催化下合成炔基化聚戊烯醇后，与叠氮试剂进行点击化学反应制备亲水性聚戊烯醇衍生物，然后再与r-聚谷氨酸进行偶联。
背景技术
聚戊烯醇(Polyprenol)是一类广泛存在于被子植物、裸子植物、细菌、真菌中的萜醇类化合物，其主要由一系列异戊烯基单元和终端异戊烯醇单元组成。由于聚戊烯醇和参与人体糖蛋白合成的多萜醇结构类似成为近年来研究的热点，并且研究者大量的实验结果已证实聚戊烯醇具有良好的抗肿瘤、抗阿尔兹海默症和抗炎活性等，使其在药品、保健品和化妆品等功能性产品领域得到极大的应用。但是，由于聚戊烯醇本身具有的强疏水性和低生物利用度，限制了其相关功能性产品的开发和应用。目前，聚戊烯醇的结构修饰研究主要有催化加氢、氧化反应、酯化反应，而这些反应常需要高温、使用剧毒有机试剂以及反应处理复杂等，导致反应不易控制。
近年来，点击化学反应由于所用原料易得、反应操作简单、反应条件温和、对氧或水不敏感以及产物收率高、选择性好等优点在化学合成方面得到了广泛的应用。天然化合物如黄酮类、多糖类、萜醇类等分子结构中含有羟基、氨基等反应性官能团，叠氮与炔的引入相对较易，通过点击化学反应可对其进行结构修饰。因此，本发明利用聚戊烯醇分子结构中的末端羟基与溴丙炔反应，将聚戊烯醇进行炔基功能化处理后，与叠氮试剂进行点击化学反应，将亲水性聚乙二醇长链和氨基活性功能基团引入到聚戊烯醇分子结构中，改善聚戊烯醇的水溶性，并赋予聚戊烯醇更强的反应活性，进一步与r-聚谷氨酸进行偶联反应，制备具有pH响应的两亲性聚戊烯醇多孔衍生物。该制备方法可增强聚戊烯醇药物本身在人体内的生物利用度和抗癌活性作用，有利于实现聚戊烯醇在药学研究或精细化学品领域的更进一步应用。
发明内容
本专利将聚乙二醇亲水长链和氨基功能基团通过点击发应生成的1，2，3-三氮唑基团创新性地链接到聚戊烯醇分子结构中，改善聚戊烯醇的水溶性，赋予聚戊烯醇新的反应活性，再与聚谷氨酸大分子进行偶联反应制备了具有pH响应的两亲性聚戊烯醇多孔衍生物。
为实现上述目的，本发明采用如下技术方案：
一种具有pH响应的两亲性聚戊烯醇多孔衍生物的制备方法，包括以下步骤：
(1)炔基化聚戊烯醇的合成：称取0.1-2g的聚戊烯醇溶于10-40mL的N，N-二甲基甲酰胺溶液中，加入0.005-0.1g的碱催化剂，在20-60℃加热回流下缓慢滴加0.05-1mL的溴丙炔，反应4-12h后，减压蒸馏除去溶剂，经乙醚纯化后得到炔基化聚戊烯醇。
(2)亲水性聚戊烯醇的制备：在Cu(I)催化下，取上述制备的炔基化聚戊烯醇0.1-2g溶于10-40mL的N，N-二甲基甲酰胺溶液中，搅拌均匀后，加入0.1-2g叠氮试剂，在温度为20-60℃，Cu(I)催化下反应4-12h后，过滤，减压蒸馏除去溶剂，用乙醚浸提纯化，冷冻干燥后，即得亲水性聚乙二醇化聚戊烯醇衍生物。
(3)pH响应性两亲聚戊烯醇多孔衍生物的制备：将经羧基活化后的r-聚谷氨酸与上述得到的聚乙二醇化聚戊烯醇0.1-2g，0-8℃反应12-24h，转入8K-14KDa透析袋透析24h后，干燥，得到具有pH响应的两亲性聚戊烯醇多孔衍生物。
所述的聚戊烯醇为桦木醇型聚戊烯醇如银杏叶聚戊烯醇、松针聚戊烯醇中的一种。
所述的碱催化剂为无水碳酸钾或0.1mol/L NaOH水溶液。
所述的亲水性叠氮试剂为氨基-二十二聚乙二醇叠氮。
与现有技术相比，本发明的有益效果是：
(1)所述聚戊烯醇衍生物的亲水性得到改善，其亲疏水分配系数较未改性聚戊烯醇的亲疏水分配系数6.20降至2.62。
(2)所述聚戊烯醇衍生物具有多孔特征，对水难溶性多霉素药物有优良的装载性，可达到60～86％的载药量。
(3)所述聚戊烯醇衍生物具有良好的pH响应性，在pH范围为5.0～7.4时，其累积释药率为54％～80％。
附图说明
图1是炔基化聚戊烯醇的合成路线
图2是聚乙二醇化聚戊烯醇的合成路线
图3是聚戊烯醇多孔衍生物的合成路线
图4是聚乙二醇化聚戊烯醇的核磁共振氢谱图
图5是聚戊烯醇多孔衍生物的核磁共振氢谱图
图6是聚戊烯醇多孔衍生物的扫描电镜图
图7是不同pH下聚戊烯醇多孔衍生物载阿霉素的释放曲线图
具体实施方式
现结合附图，对具有pH响应的两亲性聚戊烯醇多孔衍生物的制备方法进一步具体说明：
实施例1
炔基化聚戊烯醇的合成：称取1g银杏叶聚戊烯醇，在室温下超声溶解于20mL N，N-二甲基甲酰胺溶液中，加入0.05g无水碳酸钾碱催化剂，在60℃加热回流下缓慢滴加0.5mL的溴丙炔，搅拌反应8h后，减压蒸馏除去溶剂，然后经乙醚浸提纯化，得到炔基化聚戊烯醇。
亲水性聚戊烯醇衍生物的制备：称取0.8g上述得到的炔基化聚戊烯醇溶于20mLN，N-二甲基甲酰胺溶液中，搅拌均匀后，加入0.5g氨基聚乙二醇叠氮试剂，在温度为60℃，Cu(I)催化下反应12h后，过滤，减压蒸馏除去溶剂，用乙醚反复洗涤，冷冻干燥后，得到聚乙二醇化聚戊烯醇。
pH响应的两亲性聚戊烯醇多孔衍生物的制备：取上述得到的聚乙二醇化聚戊烯醇0.8g溶于8mL的乙醇溶液中，备用。将一定量r-聚谷氨酸溶于20mL水中，室温下搅拌至完全溶解，随后加入羧基活化剂EDC、NHS反应30min后，缓慢滴加聚乙二醇化聚戊烯醇乙醇溶液，在温度为0℃反应12h，然后转入8K-14K Da的透析袋中，用去离子水透析24h，冷冻干燥，得到pH响应的两亲性聚戊烯醇多孔衍生物。其亲疏水系数为2.08，阿霉素载药率为84％。
实施例2
炔基化聚戊烯醇的合成：称取0.5g松针聚戊烯醇，溶于20mL N，N-二甲基甲酰胺溶液中，加入1mL 0.1mol/L的氢氧化钠溶液，在40℃加热回流下缓慢滴加0.5mL的溴丙炔，搅拌反应4h后，减压蒸馏除去溶剂，得到固体产物，然后用乙醚浸提纯化，得到炔基化聚戊烯醇。
亲水性聚戊烯醇的制备：称取0.5g上述得到的炔基化聚戊烯醇，溶于20mL N，N-二甲基甲酰胺溶液中，搅拌均匀后，加入0.5g氨基聚乙二醇叠氮试剂，在温度为40℃，Cu(I)催化下反应10h后，过滤，减压蒸馏除去溶剂，用乙醚反复洗涤，干燥，得到亲水性聚乙二醇化聚戊烯醇。
pH响应的两亲性聚戊烯醇多孔衍生物的制备：取上述得到的聚乙二醇化聚戊烯醇0.5g溶于5mL的乙醇溶液中，备用。将一定量r-聚谷氨酸溶于20mL水中，随后在搅拌条件下，每隔5min依次加入羧基活化剂EDC、NHS、聚乙二醇化聚戊烯醇乙醇溶液，在温度为5℃反应12h，然后转入8K-14KDa的透析袋中，用去离子水透析24h，冷冻干燥，得到聚戊烯醇多孔材料。其亲疏水系数为3.68，阿霉素载药率为76％。
上述只是本发明的较佳实施例，并非对本发明作任何形式上的限制。任何熟悉本领域的技术人员，在不脱离本发明技术方案范围的情况下，都可利用上述揭示的技术内容对本发明技术方案做出许多可能的变动和修饰，或修改为等同变化的等效实施例。因此凡是未脱离本发明技术方案的内容，依据本发明技术实质对以上实施例所做的任何简单修改、等同变化及修饰，均应落在本发明技术方案保护的范围内。

Claims (9)

1.一种具有pH响应的两亲性聚戊烯醇多孔衍生物的制备方法，其特征在于包含以下步骤：
步骤一：炔基化聚戊烯醇的制备：在碱催化剂催化下，将聚戊烯醇与3-溴丙炔反应，得到炔基化聚戊烯醇，所述的聚戊烯醇为银杏叶聚戊烯醇或松针聚戊烯醇；
步骤二：亲水性聚乙二醇化聚戊烯醇衍生物的合成：将炔基化聚戊烯醇与亲水性长链叠氮试剂进行点击化学反应，得到亲水性聚乙二醇化聚戊烯醇衍生物，所述的亲水性叠氮试剂为氨基-二十二聚乙二醇叠氮；
步骤三：具有pH响应的两亲性聚戊烯醇多孔衍生物的制备
将亲水性聚乙二醇化聚戊烯醇衍生物与r-聚谷氨酸进行偶联反应，得到具有pH响应的两亲性聚戊烯醇多孔衍生物。
2.如权利要求1所述的一种具有pH响应的两亲性聚戊烯醇多孔衍生物的制备方法，其特征在于，称取0.1-2g的聚戊烯醇溶于10-40mL的N，N-二甲基甲酰胺溶液中，加入0.005-0.1g的碱催化剂，在20-60℃加热回流下缓慢滴加0.05-1mL的溴丙炔，反应4-12h后，减压蒸馏除去溶剂，经乙醚浸提纯化，得到炔基化聚戊烯醇。
3.如权利要求1所述的一种具有pH响应的两亲性聚戊烯醇多孔衍生物的制备方法，其特征在于，取步骤一得到的炔基化聚戊烯醇0.1-2g溶于10-40mL的N，N-二甲基甲酰胺溶液中，搅拌均匀后，加入0.1-2g叠氮试剂，在温度为20-60℃、Cu(I)催化下反应4-12h后，过滤，减压蒸馏除去溶剂，用乙醚浸提纯化，冷冻干燥，即得亲水性聚乙二醇化聚戊烯醇衍生物。
4.如权利要求1所述的一种具有pH响应的两亲性聚戊烯醇多孔衍生物的制备方法，其特征在于，取0.1-2g步骤二所得的亲水性聚乙二醇化聚戊烯醇衍生物和一定量经羧基活化后的r-聚谷氨酸溶于乙醇溶液，在0-8℃反应12-24h，转入8K-14K Da透析袋中透析24h，冷冻干燥后，得到具有pH响应的两亲性聚戊烯醇多孔衍生物。
5.根据权利要求1所述一种具有pH响应的两亲性聚戊烯醇多孔衍生物的制备方法，其特征在于，步骤一所述的碱催化剂为无水碳酸钾或0.1mol/L NaOH水溶液。
6.根据权利要求1所述一种具有pH响应的两亲性聚戊烯醇多孔衍生物的制备方法，其特征在于，步骤二所述的亲水性聚乙二醇化聚戊烯醇衍生物含有氨基、1，2，3-三氮唑基团和聚乙二醇长链。
7.根据权利要求1所述一种具有pH响应的两亲性聚戊烯醇多孔衍生物的制备方法，其特征在于，步骤三所述的具有pH响应的两亲性聚戊烯醇多孔衍生物呈多孔状。
8.根据权利要求1所述一种具有pH响应的两亲性聚戊烯醇多孔衍生物的制备方法，其特征在于，步骤三所述的具有pH响应的两亲性聚戊烯醇多孔衍生物具有优良的药物装载性，对阿霉素的载药量为60～86％。
9.根据权利要求1所述一种具有pH响应的两亲性聚戊烯醇多孔衍生物的制备方法，其特征在于，步骤三所述的具有pH响应的两亲性聚戊烯醇多孔衍生物在pH为5.0-7.4具有pH响应性，48h内其累积释药率为54％～80％。
CN202111365445.6A 2021-11-17 2021-11-17 一种具有pH响应的两亲性聚戊烯醇多孔衍生物的制备方法 Active CN113912854B (zh)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202111365445.6A CN113912854B (zh) 2021-11-17 2021-11-17 一种具有pH响应的两亲性聚戊烯醇多孔衍生物的制备方法

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202111365445.6A CN113912854B (zh) 2021-11-17 2021-11-17 一种具有pH响应的两亲性聚戊烯醇多孔衍生物的制备方法

Publications (2)

Publication Number Publication Date
CN113912854A CN113912854A (zh) 2022-01-11
CN113912854B true CN113912854B (zh) 2023-08-08

Family

ID=79247549

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202111365445.6A Active CN113912854B (zh) 2021-11-17 2021-11-17 一种具有pH响应的两亲性聚戊烯醇多孔衍生物的制备方法

Country Status (1)

Country Link
CN (1) CN113912854B (zh)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114854028B (zh) * 2022-05-18 2023-12-05 中国林业科学研究院林产化学工业研究所 一种肿瘤环境响应阳离子型聚戊烯醇靶向载体的制备方法

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102775276B (zh) * 2012-07-26 2014-10-01 中国林业科学研究院林产化学工业研究所 一种具有抑菌和抗氧化活性的植物聚戊烯醇及其加氢衍生物制备方法
CN102911368B (zh) * 2012-11-16 2015-05-27 苏州大学 具有酸敏感性的两亲性三嵌段共聚物、其制备方法及应用
CN105943496B (zh) * 2016-04-29 2019-01-18 中南大学 pH响应的半乳糖化壳聚糖-聚乙二醇聚合物键合阿霉素前体药物及其制备和用途
CN107141323B (zh) * 2017-06-26 2019-10-29 苏州大学 还原/pH双重响应性阿霉素前药及其制备方法与应用
CN109394700A (zh) * 2018-12-24 2019-03-01 中国林业科学研究院林产化学工业研究所 一种壳聚糖-氧化石墨烯负载聚戊烯醇-富勒烯的纳米复合物的制备方法

Also Published As

Publication number Publication date
CN113912854A (zh) 2022-01-11

Similar Documents

Publication Publication Date Title
Ferruti et al. A novel modification of poly (l‐lysine) leading to a soluble cationic polymer with reduced toxicity and with potential as a transfection agent
JP2018031020A (ja) シクロデキストリン誘導体のための製造方法
CN113912854B (zh) 一种具有pH响应的两亲性聚戊烯醇多孔衍生物的制备方法
CN110078644B (zh) 一种[2-[1-(Fmoc-氨基)乙氧基]乙氧基]乙酸的制备方法
CN102086165B (zh) Pd催化剂在生产强力霉素氢化工艺中的应用
KR20040094716A (ko) 포스포릴콜린기 함유 다당류 및 그 제조 방법
CN103319388A (zh) 一种双功能聚乙二醇衍生物及其制备方法
CN102408445A (zh) 六氨基酸酯苯氧基环三磷腈和其荧光纳米微球及制备方法
JP5371067B2 (ja) 高純度のポリエチレングリコールアルデヒド誘導体の製造方法
CN109517077B (zh) 一类苯硼酸或其衍生物改性的多糖及其制备方法和应用
CN106565860A (zh) 一种制备磺丁基醚‑β‑环糊精的方法
CN104710605A (zh) 一种单端氨基聚乙二醇单甲醚及其制备方法
CN101817764B (zh) 链状尿素衍生物、环状尿素衍生物及噁唑烷酮的制备方法
CN101591428A (zh) 一种聚酯树枝状大分子的制备方法
CN100384883C (zh) 制备壳聚糖-接枝-聚己内酯的方法
CN101195031B (zh) 葡萄糖酸改性壳聚糖亲核no供体及其合成方法
CN101081833A (zh) 2－氨基－3－氯－5－三氟甲基吡啶的制备方法
US8609900B2 (en) Dendritic macromolecule and a process thereof
CN112321636B (zh) 一种抗生素中间体的制备方法
CN114656465A (zh) 一种阿维巴坦钠的制备方法
WO2008117300A2 (en) Improved process for the preparation of cadexomer iodine
CN1975419A (zh) 一种水溶性甲壳素pH探针及其制备方法
CN115772077B (zh) 一种由阿拉伯糖醇催化转化制备手性d-甘油酸的方法
CN111484613B (zh) 一种温敏性非异氰酸酯聚氨酯及其制备方法和应用
CN1449993A (zh) 富勒醇的制备方法

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
DD01 Delivery of document by public notice

Addressee: Wang Chengzhang

Document name: Notification of completing formalities

DD01 Delivery of document by public notice
DD01 Delivery of document by public notice

Addressee: Wang Chengzhang

Document name: Notice of Handling Registration Procedures

DD01 Delivery of document by public notice
GR01 Patent grant
GR01 Patent grant