CN110772496A - 一种应用于肝癌介入治疗的紫杉醇纳米粒 - Google Patents

一种应用于肝癌介入治疗的紫杉醇纳米粒 Download PDF

Info

Publication number
CN110772496A
CN110772496A CN201811169340.1A CN201811169340A CN110772496A CN 110772496 A CN110772496 A CN 110772496A CN 201811169340 A CN201811169340 A CN 201811169340A CN 110772496 A CN110772496 A CN 110772496A
Authority
CN
China
Prior art keywords
paclitaxel
liver cancer
glycolic acid
drug
interventional therapy
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
CN201811169340.1A
Other languages
English (en)
Inventor
金成�
白玲
姜源
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.)
Xian Xd Group Hospital
Original Assignee
Xian Xd Group Hospital
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 Xian Xd Group Hospital filed Critical Xian Xd Group Hospital
Priority to CN201811169340.1A priority Critical patent/CN110772496A/zh
Publication of CN110772496A publication Critical patent/CN110772496A/zh
Pending legal-status Critical Current

Links

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
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5005—Wall or coating material
    • A61K9/5021—Organic macromolecular compounds
    • A61K9/5031—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poly(lactide-co-glycolide)
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/337—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
    • 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)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

本发明为一种应用于肝癌介入治疗的紫杉醇纳米粒。采用溶酶挥发法制备装载紫杉醇的纳米粒，其对肝癌具有明显抗肿瘤效果。通过介入途径给予紫杉醇装载纳米粒，超选给药的前后端分别予以碘油封闭，进行夹心方式治疗，可以提高肝癌的治疗效果。

Description

一种应用于肝癌介入治疗的紫杉醇纳米粒
【技术领域】
本发明属于药物剂型改进，为一种应用于肝癌介入治疗的紫杉醇纳米粒。
【背景技术】
肝癌是常见恶性肿瘤，恶性度高，治疗主要依靠以手术为主的综合治疗。由于肝癌起病隐匿，所以发现较晚，手术切除率低，而且术后复发率高。对于无法手术的肝癌患者，临床常采用常规介入和药物治疗，但总体效果并不理想。因此，开发更为有效的肝癌新治疗策略是一项重要而迫切的任务。
纳米药物是将药物制备成纳米尺度或应用纳米载体传输药物。纳米载体是指分散或装载有药物的各种纳米粒，目前已成为研究热点。与传统分子药物相比纳米药物的优点在于：纳米药物利用纳米颗粒的小尺寸效应，容易进入细胞而实现高疗效；纳米药物的比表面积大，链接或加载的功能基团或活性中心多；载体材料的性能优越，便于生物降解或吸收；纳米药物具有的多孔、中空、多层等结构特性，易于药物控制释放，改变药物在体内的半衰期，延长药物的作用时间；纳米药物通过结合抗体等配基制成靶向制剂，将药物主动输送到人体特定部位，实现低毒性和高疗效。纳米载体装载药物的技术已十分成熟，无论对于常用化疗药物单体，还是多药组合联合输送，相对于传统给药方式具有明显的优势。
给药途径是治疗成败的关键因素之一，介入治疗是肿瘤治疗的有效途径，超选给药的前后端分别予以碘油封闭，中间给予复合装载的纳米药物，累积的药物在局部高浓度释药，同时发挥其修饰的功能基团作用，这样夹心治疗法是一种理想的治疗模式。对于晚期的巨大肝癌患者，通过介入途径给予药物装载纳米粒，进行夹心方式的临床试验性治疗，开发疗效肯定的抗肿瘤新型纳米药物，具有广阔的应用前景。
【发明内容】
针对肝癌介入治疗效果的局限，本发明所述一种应用于肝癌介入治疗的紫杉醇纳米粒，能够通过夹心介入治疗法提高对肝癌的疗效。紫杉醇已应用于临床，将紫杉醇装载于纳米粒治疗肝癌在理论有基础，在临床应用上有前景。制备纳米载体的生物材料聚乳酸-羟基乙酸共聚物在体内生物降解为无毒的水和二氧化碳，美国FDA已批准其作为药物辅料用于临床。
采用单乳溶酶挥发法制备紫杉醇纳米粒。将一定质量紫杉醇溶于2.5％PLGA二氯甲烷溶液一倍体积，然后倒入1％PVA水溶液5倍体积，剧烈搅拌并超声乳化3min。生成的悬浊液持续磁力搅拌6h以挥发尽二氯甲烷，3000rpm离心弃上清，蒸馏水洗涤3遍，冷冻干燥后，纳米粒干粉4℃保存备用。
紫杉醇纳米粒载药率为4.50％，包封率为85.51％，呈光滑球形，粒径分布在100～500nm 之间，平均约300nm，模拟体外释药曲线呈双相，即在爆发释放之后为缓慢释放，1d内释放量占15％，14d内药物释放量约为30％。
紫杉醇纳米粒作用后，肝癌Huh7和HepG2细胞出现皱缩、崩解，细胞克隆形成能力降低，透射电镜观察到细胞对纳米粒的吞噬摄取，紫杉醇纳米粒组较药物单体作用更明显。Huh7 和HepG2细胞的接种率分别为87％和69％。细胞存活分析的结果指出与紫杉醇和紫杉醇纳米粒共培养的乏氧Huh7和HepG2细胞克隆形成能力较对照均显著降低，紫杉醇纳米粒的抗肿瘤作用较紫杉醇单体明显。紫杉醇纳米粒依靠被动靶向作用大量累积在Huh7移植瘤局部，具有明显增强的选择性杀伤作用。

Claims (4)

1.一种应用于肝癌介入治疗的纳米制剂,其特征在于：所属制剂包含紫杉醇和聚乳酸-羟基乙酸共聚物。其中聚乳酸-羟基乙酸共聚物为高分子生物载体材料。
2.紫杉醇纳米粒对肝癌具有明显抗肿瘤效果，通过介入途径给药，超选给药的前后端分别予以碘油封闭，进行夹心方式治疗，同时具有控释作用，可以提高疗效。
3.一种按照权利要求1所述的抗肝癌制剂，紫杉醇来源于植物提取或生物合成，聚乳酸-羟基乙酸共聚物为人工合成。
4.如权利要求1所述的药物配方中，紫杉醇和聚乳酸-羟基乙酸共聚物的质量比为1:4。制备方法：采用单乳溶酶挥发法制备紫杉醇纳米粒。将一定质量紫杉醇溶于2.5％PLGA二氯甲烷溶液一倍体积，然后倒入1％PVA水溶液5倍体积，剧烈搅拌并超声乳化3min。生成的悬浊液持续磁力搅拌6h以挥发尽二氯甲烷，3000rpm离心弃上清，蒸馏水洗涤3遍，冷冻干燥后，纳米粒干粉4℃保存备用。
CN201811169340.1A 2018-10-11 2018-10-11 一种应用于肝癌介入治疗的紫杉醇纳米粒 Pending CN110772496A (zh)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201811169340.1A CN110772496A (zh) 2018-10-11 2018-10-11 一种应用于肝癌介入治疗的紫杉醇纳米粒

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201811169340.1A CN110772496A (zh) 2018-10-11 2018-10-11 一种应用于肝癌介入治疗的紫杉醇纳米粒

Publications (1)

Publication Number Publication Date
CN110772496A true CN110772496A (zh) 2020-02-11

Family

ID=69383164

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201811169340.1A Pending CN110772496A (zh) 2018-10-11 2018-10-11 一种应用于肝癌介入治疗的紫杉醇纳米粒

Country Status (1)

Country Link
CN (1) CN110772496A (zh)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115192546A (zh) * 2022-07-15 2022-10-18 西电集团医院 一种靶向肝癌干细胞的多功能纳米粒及其制备方法

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060034925A1 (en) * 2004-04-02 2006-02-16 Au Jessie L Tumor targeting drug-loaded particles
CN1823740A (zh) * 2005-12-28 2006-08-30 中国医学科学院生物医学工程研究所 一种紫杉醇缓释纳米粒、制备方法及其应用
CN105055312A (zh) * 2015-09-07 2015-11-18 苏州纳诺康生物技术有限公司 以聚乳酸-羟基乙醇酸共聚物为材料制备多西紫杉醇纳米载药颗粒的方法

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060034925A1 (en) * 2004-04-02 2006-02-16 Au Jessie L Tumor targeting drug-loaded particles
CN1823740A (zh) * 2005-12-28 2006-08-30 中国医学科学院生物医学工程研究所 一种紫杉醇缓释纳米粒、制备方法及其应用
CN105055312A (zh) * 2015-09-07 2015-11-18 苏州纳诺康生物技术有限公司 以聚乳酸-羟基乙醇酸共聚物为材料制备多西紫杉醇纳米载药颗粒的方法

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
庞丽云等: "载紫杉醇聚乳酸聚乙醇酸共聚物纳米粒抑制人肝癌细胞HepG2的作用", 《中国组织工程研究》 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115192546A (zh) * 2022-07-15 2022-10-18 西电集团医院 一种靶向肝癌干细胞的多功能纳米粒及其制备方法

Similar Documents

Publication Publication Date Title
Li et al. Strategies to obtain encapsulation and controlled release of small hydrophilic molecules
Huang et al. New advances in gated materials of mesoporous silica for drug controlled release
Ren et al. Improved anti-colorectal carcinomatosis effect of tannic acid co-loaded with oxaliplatin in nanoparticles encapsulated in thermosensitive hydrogel
Tang et al. Multiple local therapeutics based on nano-hydrogel composites in breast cancer treatment
Zhu et al. Responsive hydrogels based on triggered click reactions for liver cancer
CN109054000B (zh) 一种基于聚水杨酸的纳米载药体系及其制备方法和应用
CN102302503B (zh) 共载柔红霉素和5–溴汉防己甲素磁性纳米四氧化三铁颗粒的制备方法
Wang et al. Two novel nanoscale preparations of micelle and thermosensitive hydrogel for docetaxel to treat malignant tumor
Chen et al. Co-delivery of hydrophilic/hydrophobic drugs by multifunctional yolk-shell nanoparticles for hepatocellular carcinoma theranostics
WO2021142884A1 (zh) 阿司匹林在血小板靶向载药系统制备中的用途
CN109771663B (zh) 一种酸响应性抗癌纳米药物的制备及应用
Zhao et al. Cell membrane-based biomimetic nanosystems for advanced drug delivery in cancer therapy: A comprehensive review
CN103520207A (zh) 靶向性顺铂纳米海藻酸钠脂质体
WO2019007019A1 (zh) 一种补骨脂素聚合物纳米粒制剂以及制备方法
Wu et al. Polysaccharide-based tumor microenvironment-responsive drug delivery systems for cancer therapy
Bai et al. Progress and principle of drug nanocrystals for tumor targeted delivery
Zhou et al. Controllable loading and release of nanodrugs in polymeric vesicles
CN112386585B (zh) 一种自组装纳米药物及其制备方法与应用
Jia et al. Preparation, physicochemical characterization and cytotoxicity in vitro of gemcitabine-loaded PEG-PDLLA nanovesicles
CN110772496A (zh) 一种应用于肝癌介入治疗的紫杉醇纳米粒
CN103655484A (zh) 一种利用自组装技术制备紫杉醇缓释微球的方法及其产品
CN109364253B (zh) 一种用于提高肿瘤组织渗透性的纳米粒子及其制备方法和应用
CN107281500A (zh) 一种阿霉素复合物及其制备方法与应用
Chen et al. Application and development of magnetic iron oxide nanoparticles in tumor targeted therapy
Fu et al. Therapeutic effects of paclitaxel loaded polyethylene glycol-polylactic acid-glycolic acid copolymer nanoparticles on pancreatic cancer in rats

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
RJ01 Rejection of invention patent application after publication
RJ01 Rejection of invention patent application after publication

Application publication date: 20200211