CN112245392A - 一种低分子量壳聚糖修饰脂肪酸载药囊泡的制备与应用 - Google Patents

一种低分子量壳聚糖修饰脂肪酸载药囊泡的制备与应用 Download PDF

Info

Publication number
CN112245392A
CN112245392A CN202011151368.XA CN202011151368A CN112245392A CN 112245392 A CN112245392 A CN 112245392A CN 202011151368 A CN202011151368 A CN 202011151368A CN 112245392 A CN112245392 A CN 112245392A
Authority
CN
China
Prior art keywords
vesicle
preparation
drug
fatty acid
weight chitosan
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.)
Pending
Application number
CN202011151368.XA
Other languages
English (en)
Inventor
蒋旻昀
陈玥
仲晶晶
单飞丹
童童
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.)
Taizhou Vocational and Technical College
Original Assignee
Taizhou Vocational and Technical College
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 Taizhou Vocational and Technical College filed Critical Taizhou Vocational and Technical College
Priority to CN202011151368.XA priority Critical patent/CN112245392A/zh
Publication of CN112245392A publication Critical patent/CN112245392A/zh
Pending legal-status Critical Current

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A61K9/127—Liposomes
    • A61K9/1271—Non-conventional liposomes, e.g. PEGylated liposomes, liposomes coated with polymers
    • A61K9/1273—Polymersomes; Liposomes with polymerisable or polymerised bilayer-forming substances
    • 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
    • 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
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/12—Carboxylic acids; Salts or anhydrides thereof
    • 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
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/08—Solutions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • General Chemical & Material Sciences (AREA)
  • Dermatology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Dispersion Chemistry (AREA)
  • Inorganic Chemistry (AREA)
  • Molecular Biology (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

本发明公开了一种低分子量壳聚糖修饰脂肪酸载药囊泡的制备与应用，包括以下步骤：1)将油酸加入到NaOH水溶液中，室温下搅拌，然后加入低分子量壳聚糖溶解，制得混合囊泡；2)将药物加入到步骤1)所得混合囊泡中，搅拌一段时间后静置使药物载入囊泡，得到载药囊泡溶液。本发明低分子量壳聚糖包覆于脂肪酸囊泡表面，在中性pH范围内制备稳定得混合囊泡，可实现药物的高效负载和可控释放，粒径在100～200nm之间。

Description

一种低分子量壳聚糖修饰脂肪酸载药囊泡的制备与应用
技术领域
本发明涉及药物技术领域，具体涉及一种低分子量壳聚糖修饰脂肪酸载药囊泡的制备与应用。
背景技术
脂肪酸分子结构简单，价格低廉，在pKa附近自组装形成脂肪酸囊泡，具有优良的生物相容性及pH响应性，然而脂肪酸囊泡的pH窗口均偏碱性范围，限制了其在生理条件下的应用。现有技术多采用
壳聚糖为天然多糖甲壳素脱除部分乙酰基的产物，具有生物降解性、细胞亲和性和生物活性等许多独特的物理化学性质，是天然多糖中唯一的碱性多糖。壳聚糖降解后的低分子量壳聚糖，内氢键作用减弱，具有较好的水溶性，具有的多羟基、多氨基结构功能作用大，生物活性高。
发明内容
本发明针对现有技术的不足，提出了一种低分子量壳聚糖修饰脂肪酸载药囊泡的制备与应用。
本发明可以通过以下技术方案实现：
一种低分子量壳聚糖修饰脂肪酸载药囊泡的制备方法，包括以下制备步骤：
1)将脂肪酸加入到NaOH水溶液中，室温下搅拌，然后加入低分子量壳聚糖，搅拌0.5～1h至全部溶解，静置24h自组装，制得混合囊泡；
2)将药物加入到步骤1)所述的混合囊泡中，搅拌使药物载入囊泡空腔中，得到载药囊泡溶液。
步骤1)中，脂肪酸为油酸或亚油酸，浓度为10～30mmol/L。
步骤1)中，NaOH水溶液溶度为10～20mmol/L
步骤1)中，低分子量壳聚糖分子量为179至10000左右，链节摩尔浓度为5～20mmol/L。
步骤1)中，控制壳聚糖链节与脂肪酸的摩尔比为0.4～1:1。
步骤2)中，所述抗癌药物包括阿霉素。
步骤2)中，载药囊泡用于制成注射液、注射用冻干粉剂、透皮制剂或植入制剂的一种剂型。
根据上述制备方法制备的载药囊泡，用于制成注射液、注射用冻干粉剂、透皮制剂或植入制剂。
根据上述制备方法制备的载药囊泡，在制备抗肿瘤药物中的应用。
本发明的有益效果是：
1)本发明的方法制备得到的载药囊泡可在中性pH实现，适合人体生理要求；
2)可实现药物的可控释放；
3)具有空心结构，粒径在100～200nm之间；
4)制备工艺简单，易于操作和实现。
附图说明
图1为本发明所得载药囊泡的透射电镜图；
图2为实施例1的载药囊泡缓释曲线。
具体实施方式
下面结合实施例对本发明作进一步描述。以下实施例只是用于更加清楚地说明本发明的性能，而不能仅局限于下面的实施例。
实施例1
本实施例中基于低分子量壳聚糖修饰油酸载药囊泡的制备方法，其步骤为：
1)将适量油酸加入到20mmol/LNaOH水溶液中，室温下搅拌，制备得到20mmol/L油酸钠溶液。然后加入等体积的链节摩尔浓度15mmmol/L的低分子量壳聚糖，搅拌0.5～1h至全部溶解后，调节pH至6.5，静置24h自组装，制得混合囊泡；
2)将1mg阿霉素加入到步骤1)的混合囊泡中，搅拌使药物载入囊泡空腔中，然后在蒸馏水中透析140分钟，得到载药囊泡溶液，载药量为42.7％。
实施例2
本实施例中基于低分子量壳聚糖修饰油酸载药囊泡的制备方法，其步骤为：
1)将适量亚亚油酸加入到20mmol/LNaOH水溶液中，室温下搅拌，制备得到20mmol/L油酸钠溶液。然后加入等体积的链节摩尔浓度15mmmol/L的低分子量壳聚糖，搅拌0.5～1h至全部溶解，静置24h自组装，制得混合囊泡；
2)将1mg阿霉素加入到步骤1)的混合囊泡中，搅拌使药物载入囊泡空腔中，然后在蒸馏水中透析140分钟，得到载药囊泡溶液，载药量为35.0％。
为了验证本发明所得载药囊泡的药物控释和缓释效果，我们进行了药物的控释和缓释效果的测试，具体结果如图2所示：
由图2可以看到，囊泡粒径100～200nm左右，药物未经囊泡负载140分钟直接释放100％，药物经囊泡负载在12小时内累计释放率只有44％。
以上已以较佳实施例公开了本发明，然其并非用以限制本发明，凡采用等同替换或者等效变换方式所获得的技术方案，均落在本发明的保护范围之内。

Claims (8)

1.一种低分子量壳聚糖修饰脂肪酸载药囊泡的制备方法，其特征在于，包括以下制备步骤：
1)将脂肪酸加入到NaOH水溶液中，室温下搅拌，然后加入低分子量壳聚糖溶解，搅拌0.5～1h，静置24h自组装，制得混合囊泡；
2)将药物加入到步骤1)所述的混合囊泡中，搅拌使药物载入囊泡空腔中，得到载药囊泡溶液。
2.根据权利要求1所述的制备方法，其特征在于，所述的脂肪酸为油酸或亚油酸，浓度为10～30mmol/L。
3.根据权利要求1所述的制备方法，其特征在于，所述的NaOH水溶液溶度为10～20mmol/L。
4.根据权利要求1所述的制备方法，其特征在于，所述的低分子量壳聚糖分子量为179至10000，链节摩尔浓度为5～20mmol/L。
5.根据权利要求1所述的制备方法，其特征在于，控制壳聚糖链节与脂肪酸的摩尔比为0.4～1:1。
6.根据权利要求1所述的制备方法，其特征在于，所述药物为抗癌药物，优选阿霉素。
7.根据权利要求1-6任一项制备方法制备的载药囊泡，用于制成注射液、注射用冻干粉剂、透皮制剂或植入制剂。
8.根据权利要求1-6任一项制备方法制备的载药囊泡，在制备抗肿瘤药物中的应用。
CN202011151368.XA 2020-10-25 2020-10-25 一种低分子量壳聚糖修饰脂肪酸载药囊泡的制备与应用 Pending CN112245392A (zh)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202011151368.XA CN112245392A (zh) 2020-10-25 2020-10-25 一种低分子量壳聚糖修饰脂肪酸载药囊泡的制备与应用

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202011151368.XA CN112245392A (zh) 2020-10-25 2020-10-25 一种低分子量壳聚糖修饰脂肪酸载药囊泡的制备与应用

Publications (1)

Publication Number Publication Date
CN112245392A true CN112245392A (zh) 2021-01-22

Family

ID=74262360

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202011151368.XA Pending CN112245392A (zh) 2020-10-25 2020-10-25 一种低分子量壳聚糖修饰脂肪酸载药囊泡的制备与应用

Country Status (1)

Country Link
CN (1) CN112245392A (zh)

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101406454A (zh) * 2008-11-14 2009-04-15 沈阳药科大学 低分子量壳聚糖修饰的脂质体及其制备方法
CN102863557A (zh) * 2012-10-12 2013-01-09 苏州大学 乳糖酸修饰的脂肪酸-三甲基壳聚糖聚合物制备方法及应用
CN103948914A (zh) * 2014-05-14 2014-07-30 广东石油化工学院 一种可载药的低分子量水溶性壳聚糖纳米粒子的制备方法
CN108739807A (zh) * 2018-06-21 2018-11-06 中国热带农业科学院农产品加工研究所 植物油酸-壳聚糖基纳米微胶囊农药、其制备方法及其应用
CN109810287A (zh) * 2019-01-28 2019-05-28 扬州大学 一种壳聚糖季铵盐-脂肪酸囊泡的制备方法
CN110974976A (zh) * 2019-12-16 2020-04-10 天津市第三中心医院 羧甲基壳聚糖修饰载药囊泡及其制备与应用

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101406454A (zh) * 2008-11-14 2009-04-15 沈阳药科大学 低分子量壳聚糖修饰的脂质体及其制备方法
CN102863557A (zh) * 2012-10-12 2013-01-09 苏州大学 乳糖酸修饰的脂肪酸-三甲基壳聚糖聚合物制备方法及应用
CN103948914A (zh) * 2014-05-14 2014-07-30 广东石油化工学院 一种可载药的低分子量水溶性壳聚糖纳米粒子的制备方法
CN108739807A (zh) * 2018-06-21 2018-11-06 中国热带农业科学院农产品加工研究所 植物油酸-壳聚糖基纳米微胶囊农药、其制备方法及其应用
CN109810287A (zh) * 2019-01-28 2019-05-28 扬州大学 一种壳聚糖季铵盐-脂肪酸囊泡的制备方法
CN110974976A (zh) * 2019-12-16 2020-04-10 天津市第三中心医院 羧甲基壳聚糖修饰载药囊泡及其制备与应用

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
LEIMING GUO.ET.AL: "Self-assembled vesicles of sodium oleate and chitosan", 《COLLOID AND POLYMER SCIENCE》 *
蒋旻昀等: "壳聚糖辅助共轭亚油酸制备混合脂肪酸囊泡", 《中国化学会第17 届胶体与界面化学学术会议论文（摘要）集》 *

Similar Documents

Publication Publication Date Title
George et al. Guar gum: Versatile natural polymer for drug delivery applications
Gim et al. Carbohydrate‐based nanomaterials for biomedical applications
Qiu et al. A review of green techniques for the synthesis of size-controlled starch-based nanoparticles and their applications as nanodelivery systems
US7740883B2 (en) Nanoparticles from chitosan
Gonzalez-Gaitano et al. Drug carrier systems based on cyclodextrin supramolecular assemblies and polymers: present and perspectives
Prabaharan et al. Carboxymethyl chitosan-graft-phosphatidylethanolamine: Amphiphilic matrices for controlled drug delivery
EP2285825B1 (en) Method of forming non-immunogenic hydrophobic protein nanoparticles and uses therefor
CN110384684B (zh) 一种单羧基壳聚糖/紫草素复合纳米颗粒及其制备方法
Bao et al. The influence of solvent formulations on thermosensitive hydroxybutyl chitosan hydrogel as a potential delivery matrix for cell therapy
Maiti et al. Smart nanopolysaccharides for the delivery of bioactives
de Souza et al. Pullulan as a sustainable biopolymer for versatile applications: A review
CN111514097B (zh) 一种核桃壳多酚的pH响应型纳米水凝胶的制备方法
Sirisha et al. Polysaccharide-based nanoparticles as drug delivery systems
CN111471193A (zh) 一种双醛多糖纳米颗粒交联胶原水凝胶及其制备方法
S Verma et al. Xanthan gum a versatile biopolymer: current status and future prospectus in hydro gel drug delivery
WO2013037965A2 (en) Ionic gel
Chowdhury et al. Biocomposites of alginates in drug delivery
Yun et al. Dual-modified starch micelles as a promising nanocarrier for doxorubicin
CN114557957A (zh) 一种可注射型原位交联疏水药物缓释水凝胶的制备方法
Jana et al. Micro-and Nanoengineered Gum-Based Biomaterials for Drug Delivery and Biomedical Applications
CN112245392A (zh) 一种低分子量壳聚糖修饰脂肪酸载药囊泡的制备与应用
Sarkar et al. Modified alginates in drug delivery
Celia Monteiro de Paula et al. Polysaccharide based copolymers as supramolecular systems in biomedical applications
Patil et al. Crosslinking of polysaccharides: methods and applications
CN103948914A (zh) 一种可载药的低分子量水溶性壳聚糖纳米粒子的制备方法

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
WD01 Invention patent application deemed withdrawn after publication

Application publication date: 20210122

WD01 Invention patent application deemed withdrawn after publication